Comprehensive Organic Functional Group Transformations II: v. 6(Carbon with Three or Four Attached Heteroatoms )

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Author: Alan R. Katritzky | Richard J. K. Taylor and Eric F. V. Scriven

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Editors-in-Chief Professor Alan R. Katritzky, FRS University of Florida, Gainesville, FL, USA

Professor Richard J. K. Taylor University of York, York, UK

Editors-in-Chief Alan Katritzky, educated at Oxford, held faculty positions at Cambridge and East Anglia before migrating in 1980 to the University of Florida, where he is Kenan Professor and Director of the Center for Heterocyclic Compounds. He has trained some 800 graduate students and postdocs, and lectured and consulted worldwide. He led the team which produced Comprehensive Heterocyclic Chemistry and its sequel CHECII, has edited Advances in Heterocyclic Chemistry, Vols. 1 through 86 and conceived the plan for Comprehensive Organic Functional Group Transformations. He founded Arkat-USA, a nonprofit organization which publishes Archive for Organic Chemistry (ARKIVOC) electronic journal completely free to authors and readers at (www.arkat-usa.org). Honors include 11 honorary doctorates from eight countries and membership or foreign membership of the National Academies of Britain, Catalonia, India, Poland, Russia, and Slovenia.

Richard Taylor is currently Professor of Organic Chemistry at the University of York, where his research focuses on the development of novel synthetic methodology and the synthesis of natural products and related compounds of biological/medicinal interest. The methodology is concentrated primarily on organometallic, organosulfur, and oxidation processes, and the targets include amino acids, carbohydrates, prostaglandins, and polyene and polyoxygenated natural products, particularly with activity as antibiotics and anti-cancer agents. Richard Taylor is a graduate and postgraduate of the University of Sheffield. After his studies at Sheffield, he carried out postdoctoral research at Syntex, California (Dr. I. T. Harrison) and University College London (Professor F. Sondheimer). His first academic appointment was at the Open University in Milton Keynes. This post gave Professor Taylor the opportunity to contribute to Open University textbooks, radio programs and television productions on various aspects of organic chemistry. Professor Taylor then moved to UEA, Norwich, where he established his independent research program, before taking up his present position in York in 1993. Richard Taylor has just finished his term as President of the Organic Division of the Royal Society of Chemistry and was awarded the 1999 RSC Tilden Lectureship and the 1999 RSC Heterocyclic Prize. He is currently the UK Regional Editor of the international journal Tetrahedron.

Volume Editors EDITOR OF VOLUME 1 Janine Cossy did her undergraduate and graduate studies at the University of Reims. After a postdoctoral stay with Barry Trost, for two years (1980–1982) at the University of Wisconsin, she returned to Reims, where she became a Director of Research of the CNRS in 1990. In the same year she moved to Paris to become Professor of Organic Chemistry at the ESPCI (Ecole Supe´rieure de Physique et de Chimie Industrielles de la Ville de Paris). She is interested in synthetic methodologies (radicals, organometallics, photochemistry, thermal reactions, ring expansions, enantioselectivity, synthesis of heterocycles, synthesis of solid support) and in their applications to the synthesis of natural products and biologically active molecules.

EDITOR OF VOLUME 2 Chris Ramsden was born in Manchester, UK in 1946. He is a graduate of Sheffield University and received his Ph.D. (W. D. Ollis) in 1970 and D.Sc. in 1990. After postdoctoral work at the University of Texas (M. J. S. Dewar)(1971–1973) and University of East Anglia (A. R. Katritzky)(1973–1976), he worked in the pharmaceutical industry. He moved to Keele University as Professor of Organic Chemistry in 1992. His research interests are heterocycles and three-center bonds and applications of their chemistry to biological problems.

EDITOR OF VOLUME 3 Keith Jones was born in Manchester. He studied at Cambridge University for his B.A. in Natural Sciences (1976) and stayed to carry out research with Professor Sir Alan Battersby obtaining his Ph.D. in 1979. In 1979, he moved to a lectureship at King’s College London. In 1984, he caught up with his postdoctoral research by spending a year working with Professor Gilbert Stork at Columbia University, New York. After returning to King’s College, he became a reader in 1995. In 1998, he moved to a chair in organic and medicinal chemistry at Kingston University. His research interests cover natural product synthesis, heterocyclic chemistry and the use of radicals in synthesis. He has been a visiting professor at Neuchatel and Barcelona Universities as well as the Australian National University.

EDITOR OF VOLUME 4 Professor Gary Molander was born in Cedar Rapids, Iowa. He received his B.S. degree at Iowa State University and subsequently entered the graduate chemistry program at Purdue University in 1975, obtaining his Ph.D. degree in 1979 under the direction of Professor Herbert C. Brown. He joined Professor Barry Trost’s group at the University of Wisconsin, Madison 1980 as a postdoctoral research associate, and in 1981 he accepted an appointment at the University of Colorado, Boulder, as an Assistant Professor of chemistry, where he rose through the academic ranks. In 1999 he joined the faculty at the University of Pennsylvania, and in 2001 was appointed Allan Day Professor of Chemistry. Professor Molander’s research interests focus on the development of new synthetic methods for organic synthesis and natural product synthesis. A major focus of his research has been the application of organolanthanide reagents and catalysts to selective organic synthesis.

EDITOR OF VOLUME 5 Ray Jones started his chemistry career as an undergraduate and then completing a Ph.D. at Cambridge University under the supervision of Professor Sir Alan Battersby, in the area of alkaloid biosynthesis. After a year as an ICI Postdoctoral Fellow in the laboratories of Professor Albert Eschenmoser at the ETH Zurich, he was appointed as Lecturer in Organic Chemistry at University of Nottingham in 1974. He progressed to Senior Lecturer at Nottingham and then took up the Chair of Organic Chemistry at the Open University in 1995, before moving to the Chair of Organic and Biological Chemistry at Loughborough University in 2000. His research interests span heterocyclic and natural product chemistry, with over 100 publications. Example topics include the acyltetramic acids and pyridones, Mammea coumarins, spermine and spermidine alkaloids, imidazolines as templates for (asymmetric) synthesis, dipolar cycloadditions, and unusual amino acids and peptide mimetics.

EDITOR OF VOLUME 6 Eric F. V. Scriven is a native of Wales, UK. After working at BISRA and ESSO Ltd, he attended the University of Salford and graduated in 1965. He obtained his M.Sc. from the University of Guelph, and his Ph.D. from the University of East Anglia (with Professor A. R. Katritzky) in 1969. After postdoctoral years at the University of Alabama and University College London, he was appointed Lecturer in organic chemistry at the University of Salford. There, his research interests centered on the reactivity of azides and nitrenes. While at Salford, he spent two semesters on secondment at the University of Benin in Nigeria. He joined Reilly Industries Inc. in 1979 and was director of Research from 1991 to 2003. He is currently at the University of Florida. He edited Azides & Nitrenes (1984), and he and Professor H. Suschitzky were founding editors of Progress in Heterocyclic Chemistry, which has been published annually since 1989 by the International Society of Heterocyclic Chemistry. He also collaborated with Professors A. R. Katritzky and C. W. Rees as Editors-in-Chief of Comprehensive Heterocyclic Chemistry II (1997). His current research interests are in novel nitration reactions, ionic liquids, and applications of polymers in organic synthesis.

Preface Comprehensive Organic Functional Group Transformations (COFGT 1995) presented the vast subject of organic synthesis in terms of the introduction and interconversion of functional groups, according to a rigorous system, designed to cover all known and as yet unknown functional groups. Comprehensive Organic Functional Group Transformations II (COFGT-II), designed for specialist and nonspecialist chemists, active in academic, industrial, and government laboratories, now updates the developments of functional group transformations since the publication of the COFGT 1995. COFGT-II is structured in precisely the same manner as the original COFGT work, allowing truly comprehensive coverage of all organic functional group transformations. COFGT-II, in combination with COFGT 1995, provides an essential reference source for the all-important topic of methodologies for the interconversion of functional groups in organic compounds, and provides an efficient first point of entry into the key literature and background material for those planning any research involving the synthesis of new organic compounds. With the increase in our understanding of the way in which the chemical structure of compounds determines all physical, chemical, biological, and technological properties, targeted synthesis becomes ever more important. The making of compounds is germane not only to organic chemistry but also to future developments in all biological, medical, and materials sciences. The availability of the work in electronic format through ScienceDirect will greatly enhance its utility. The Editors-in-Chief would like to extend their warm thanks to the Volume Editors, the chapter authors, and the Elsevier staff for operating in such an efficient and professional manner. A. R. Katritzky R. J. K. Taylor

Introduction to Volume 6 Volume 6 is in four parts. Part I deals with tetracoordinate carbons bearing three heteroatoms. Part II covers tetracoordinate compounds bearing four heteroatoms, i.e., substituted methanes, and Part III deals with tricoordinate systems bearing three heteroatoms, i.e., where one heteroatom is attached to a double bond. Part IV is brief and deals with stabilized radicals, carbocations, and carbanions. Volume 6 covers a very broad area of chemistry and, even at the time of writing this second edition, many gaps in the development of organic chemistry still exist. The organization within the three parts not only follows the same broad logic developed in the previous volumes, but also has a structure unique to the multiheteroatom volume. According to the Latest Placement Principle, CF3C(NR2)3 appears in the chapter dealing with the carbons bearing three nitrogens (Chapter 6.5), not that dealing with carbons bearing three halogens (Chapter 6.1), while (CF3CH2O)2CO appears in Part III, not in Part I. In the chapter dealing with the iminocarbonyl function in Part III, the substituents on nitrogen are discussed in each appropriate subsection in the order outlined above.Thus, the RN = group would be first considered with R = H, then alkyl, alkenyl, aryl and hetaryl, alkynyl, and then heteroatom substituents in the usual order. Each chapter is divided into sections and subsections which follow the same numbering system that was used for the first edition. Where no significant new work has appeared in a specific area since the publication the first edition of Comprehensive Organic Functional Group Transformations in 1995, this is stated. This should allow readers to judge readily the scope and intensity of work outside their immediate area of expertise. Many growth areas are discussed, for example, the increase in the number and variety of methods for the introduction of a trifluoromethyl group into aromatic and aliphatic molecules (Chapter 6.1). Another instance is a metathesis reaction that involves the reaction of a metal or metalloid halide with a trimethyllithiomethane derivative such as (Me3Si)3CLi that promises general application for the synthesis of methanes that bear up to four metal or metalloid functions, many examples of which have yet to be made (Chapter 6.13). E. F. V. Scriven Florida, USA

Explanation of the reference system Throughout this work, references are designated by a number-lettering coding of which the first four numbers denote the year of publication, the next one to three letters denote the journal, and the final numbers denote the page. This code appears in the text each time a reference is quoted. This system has been used successfully in previous publications and enables the reader to go directly to the literature reference cited, without first having to consult the bibliography at the end of each chapter. The following additional notes apply: 1. A list of journal codes in alphabetical order, together with the journals to which they refer is given immediately following these notes. Journal names are abbreviated throughout using the CASSI ‘‘Chemical Abstracts Service Source Index’’ system. 2. The references cited in each chapter are given at the end of the individual chapters. 3. The list of references is arranged in order of (a) year, (b) journal in alphabetical order of journal code, (c) part letter or number if relevant, (d) volume number if relevant, and (e) page number. 4. In the reference list the code is followed by (a) the complete literature citation in the conventional manner and (b) the number(s) of the page(s) on which the reference appears, whether in the text or in tables, schemes, etc. 5. For non-twentieth-century references, the year is given in full in the code. 6. For journals which are published in separate parts, the part letter or number is given (when necessary) in parentheses immediately after the journal code letters. 7. Journal volume numbers are not included in the code numbers unless more than one volume was published in the year in question, in which case the volume number is included in parentheses immediately after the journal code letters. 8. Patents are assigned appropriate three-letter codes. 9. Frequently cited books are assigned codes. 10. Less common journals and books are given the code ‘‘MI’’ for miscellaneous with the whole code for books prefixed by the letter ‘‘B-’’. 11. Where journals have changed names, the same code is used throughout, e.g., CB refers to both Chem. Ber. and to Ber. Dtsch. Chem. Ges.

JOURNAL ABBREVIATIONS AAC ABC AC ACA AC(P) AC(R) ACH ACR ACS ACS(A) ACS(B) AF AFC AG AG(E) AHC AHCS AI AJC AK AKZ AM AMLS AMS ANC ANL ANY AOC AP APO APOC APS AQ AR AR(A) AR(B) ARP ASI ASIN AX AX(A) AX(B) B BAP BAU BBA BBR BCJ BEP BJ BJP BMC BMCL BOC BP BPJ BRP BSB BSF BSF(2) BSM C CA CAN CAR CAT CB CBR CC CCA CCC CCHT CCR CE CEJ CEN CHE CHECI CHECII CHIR CI(L) CI(M) CJC CJS CL

Antimicrob. Agents Chemother. Agric. Biol. Chem. Appl. Catal. Aldrichim. Acta Ann. Chim. (Paris) Ann. Chim. (Rome) Acta Chim. Acad. Sci. Hung. Acc. Chem. Res. Acta Chem. Scand. Acta Chem. Scand., Ser. A Acta Chem. Scand., Ser. B Arzneim.-Forsch. Adv. Fluorine Chem. Angew. Chem. Angew. Chem., Int. Ed. Engl. Adv. Heterocycl. Chem. Adv. Heterocycl. Chem. Supplement Anal. Instrum. Aust. J. Chem. Ark. Kemi Arm. Khim. Zh. Adv. Mater. (Weinheim, Ger.) Adv. Mol. Spectrosc. Adv. Mass Spectrom. Anal. Chem. Acad. Naz. Lincei Ann. N. Y. Acad. Sci. Adv. Organomet. Chem. Arch. Pharm. (Weinheim, Ger.) Adv. Phys. Org. Chem. Appl. Organomet. Chem. Adv. Polym. Sci. An. Quim. Annu. Rep. Prog. Chem. Annu. Rep. Prog. Chem., Sect. A Annu. Rep. Prog. Chem., Sect. B Annu. Rev. Phys. Chem. Acta Chim. Sin. Engl. Ed. Acta Chim. Sin. Acta Crystallogr. Acta Crystallogr., Part A Acta Crystallogr., Part B Biochemistry Bull. Acad. Pol. Sci., Ser. Sci. Chim. Bull. Acad. Sci. USSR, Div. Chem. Sci. Biochim. Biophys. Acta Biochem. Biophys. Res. Commun. Bull. Chem. Soc. Jpn. Belg. Pat. Biochem. J. Br. J. Pharmacol. Biorg. Med. Chem. Biorg. Med. Chem. Lett. Bioorg. Chem. Biochem. Biopharmacol. Br. Polym. J. Br. Pat. Bull. Soc. Chim. Belg. Bull. Soc. Chim. Fr. Bull. Soc. Chim. Fr., Part 2 Best Synthetic Methods Chimia Chem. Abstr. Cancer Carbohydr. Res. Chim. Acta Turc. Chem. Ber. Chem. Br. J. Chem. Soc., Chem. Commun. Croat. Chem. Acta Collect. Czech. Chem. Commun. Comb. Chem. High T. Scr. Coord. Chem. Rev. Chem. Express Chem. -Eur. J. Chem. Eng. News Chem. Heterocycl. Compd. (Engl. Transl.) Comp. Heterocycl. Chem., 1st edn. Comp. Heterocycl. Chem., 2nd edn. Chirality Chem. Ind. (London) Chem. Ind. (Milan) Can. J. Chem. Canadian J. Spectrosc. Chem. Lett.

CLY CM CMC COC COFGT COMCI CONAP COS CP CPB CPH CPL CR CR(A) CR(B) CR(C) CRAC CRV CS CSC CSR CT CUOC CZ CZP DIS DIS(B) DOK DOKC DP E EC EF EGP EJI EJM EJO EUP FCF FCR FES FOR FRP G GAK GC GEP GSM H HAC HC HCA HCO HOU HP IC ICA IEC IJ IJC IJC(A) IJC(B) IJM IJQ IJS IJS(A) IJS(B) IS IZV JA JAN JAP JAP(K) JBC JC JCA JCC JCO JCE JCED JCI JCP JCPB JCR(M) JCR(S)

Chem. Listy Chem. Mater. Comp. Med. Chem. Comp. Org. Chem. Comp. Org. Func. Group Transformations Comp. Organomet. Chem., 1st edn. Comp. Natural Products Chem. Comp. Org. Synth. Can. Pat. Chem. Pharm. Bull. Chem. Phys. Chem. Phys. Lett. C.R. Hebd. Seances Acad. Sci. C.R. Hebd. Seances Acad. Sci., Ser. A C.R. Hebd. Seances Acad. Sci., Ser. B C.R. Hebd. Seances Acad. Sci., Ser. C. Crit. Rev. Anal. Chem. Chem. Rev. Chem. Scr. Cryst. Struct. Commun. Chem. Soc. Rev. Chem. Tech. Curr. Org. Chem. Chem.-Ztg. Czech. Pat. Diss. Abstr. Diss. Abstr. Int. B Dokl. Akad. Nauk SSSR Dokl. Chem. (Engl. Transl.) Dyes Pigm. Experientia Educ. Chem. Energy Fuels Ger. (East) Pat. Eur. J. Inorg. Chem. Eur. J. Med. Chem. Eur. J. Org. Chem. Eur. Pat. Fortschr. Chem. Forsch. Fluorine Chem. Rev. Farmaco Ed. Sci. Fortschr. Chem. Org. Naturst. Fr. Pat. Gazz. Chim. Ital. Gummi Asbest Kunstst. Green Chem. Ger. Pat. Gen. Synth. Methods Heterocycles Heteroatom Chem. Chem. Heterocycl. Compd. [Weissberger-Taylor series] Helv. Chim. Acta Heterocycl. Commun. Methoden Org. Chem. (Houben-Weyl) Hydrocarbon Process Inorg. Chem. Inorg. Chim. Acta Ind. Eng. Chem. Res. Isr. J. Chem. Indian J. Chem. Indian J. Chem., Sect. A Indian J. Chem., Sect. B Int. J. Mass Spectrom. Ion Phys. Int. J. Quantum Chem. Int. J. Sulfur Chem. Int. J. Sulfur Chem., Part A Int. J. Sulfur Chem., Part B Inorg. Synth. Izv. Akad. Nauk SSSR, Ser. Khim. J. Am. Chem. Soc. J. Antibiot. Jpn. Pat. Jpn. Kokai J. Biol. Chem. J. Chromatogr. J. Catal. J. Coord. Chem. J. Comb. Chem. J. Chem. Ed. J. Chem. Eng. Data J. Chem. Inf. Comput. Sci. J. Chem. Phys. J. Chim. Phys. Physico-Chim. Biol. J. Chem. Res. (M) J. Chem. Res. (S)

JCS JCS(A) JCS(B) JCS(C) JCS(D) JCS(F1) JCS(F2) JCS(P1) JCS(P2) JCS(S2) JEC JEM JES JFA JFC JGU JHC JIC JINC JLC JMAC JMAS JMC JMOC JMR JMS JNP JOC JOM JOU JPC JPJ JPO JPP JPR JPS JPS(A) JPU JSC JSP JST K KFZ KGS KO KPS L LA LC LS M MC MCLC MI MIP MM MP MRC MS N NAT NEP NJC NJC NKK NKZ NMR NN NZJ OBC OCS OL OM OMR OMS OPP OPRD OR OS OSC P PA PAC PAS

J. Chem. Soc. J. Chem. Soc. (A) J. Chem. Soc. (B) J. Chem. Soc. (C) J. Chem. Soc., Dalton Trans. J. Chem. Soc., Faraday Trans. 1 J. Chem. Soc., Faraday Trans. 2 J. Chem. Soc., Perkin Trans. 1 J. Chem. Soc., Perkin Trans. 2 J. Chem. Soc., (Suppl. 2) J. Electroanal. Chem. Interfacial Electrochem. J. Energ. Mater. J. Electron Spectrosc. J. Sci. Food Agri. J. Fluorine Chem. J. Gen. Chem. USSR (Engl. Transl.) J. Heterocycl. Chem. J. Indian Chem. Soc. J. Inorg. Nucl. Chem. J. Liq. Chromatogr. J. Mater. Chem. J. Mater. Sci. J. Med. Chem. J. Mol. Catal. J. Magn. Reson. J. Mol. Sci. J. Nat. Prod. J. Org. Chem. J. Organomet. Chem. J. Org. Chem. USSR (Engl. Transl.) J. Phys. Chem. J. Pharm. Soc. Jpn. J. Phys. Org. Chem. J. Pharm. Pharmacol. J. Prakt. Chem. J. Pharm. Sci. J. Polym. Sci., Polym. Chem., Part A J. Phys. Chem. USSR (Engl. Transl.) J. Serbochem. Soc. J. Mol. Spectrosc. J. Mol. Struct. Kristallografiya Khim. Farm. Zh. Khim. Geterotsikl. Soedin. Kirk-Othmer Encyc. Khim. Prir. Soedin. Langmuir Liebigs Ann. Chem. Liq. Cryst. Life. Sci. Monatsh. Chem. Mendeleev Communications Mol. Cryst. Liq. Cryst. Miscellaneous [journal or B-yyyyMI for book] Miscellaneous Pat. Macromolecules Mol. Phys. Magn. Reson. Chem. Q. N. Porter and J. Baldas, ‘Mass Spectrometry of Heterocyclic Compounds’, Wiley, New York, 1971 Naturwissenschaften Nature Neth. Pat. Nouv. J. Chim. New J. Chem. Nippon Kagaku Kaishi (J. Chem. Soc. Jpn.) Nippon Kagaku Zasshi T. J. Batterham, ‘NMR Spectra of Simple Heterocycles’, Wiley, New York, 1973 Nucleosides & Nucleotides N. Z. J. Sci. Technol. Organic and Biomolecular Chemistry Organomet. Synth. Org. Lett. Organometallics Org. Magn. Reson. Org. Mass Spectrom. Org. Prep. Proced. lnt. Org. Process Res. Dev. Org. React. Org. Synth. Org. Synth., Coll. Vol. Phytochemistry Polym. Age Pure Appl. Chem. Pol. Acad. Sci.

PB PC PCS PH PHA PHC PIA PIA(A) PJC PJS PMH PNA POL PP PRS PS QR QRS QSAR RC RCB RCC RCM RCP RCR RHA RJ RJGC RJOC RP RRC RS RTC RZC S SA SA(A) SAP SC SCI SH SL SM SR SRC SRI SS SSR SST SUL SZP T T(S) TA TAL TCA TCC TCM TFS TH TL TS UK UKZ UP URP USP WOP YGK YZ ZAAC ZAK ZC ZN ZN(A) ZN(B) ZOB ZOR ZPC ZPK

Polym. Bull. Personal Communication Proc. Chem. Soc. ‘Photochemistry of Heterocyclic Compounds’, O. Buchardt, Ed.; Wiley, New York, 1976 Pharmazi Prog. Heterocycl. Chem. Proc. Indian Acad. Sci. Proc. Indian Acad. Sci., Sect. A Pol. J. Chem. Pak. J. Sci. Ind. Res. Phys. Methods Heterocycl. Chem. Proc. Natl. Acad. Sci. USA Polyhedron Polym. Prepr. Proceed. Roy. Soc. Phosphorus Sulfur (formerly); Phosphorus Sulfur Silicon (currently) Q. Rev., Chem. Soc. Quart. Rep. Sulfur Chem. Quant. Struct. Act. Relat. Rubber Chem. Technol. Russian Chemical Bull. Rodd’s Chemistry of Carbon Compounds Rapid Commun. Mass Spectrom. Rec. Chem. Prog. Russ. Chem. Rev. (Engl. Transl.) Rev. Heteroatom. Chem. Rubber J. Russ. J. Gen. Chem. (Engl. Transl.) Russ. J. Org. Chem. (Engl. Transl.) Rev. Polarogr. Rev. Roum. Chim. Ric. Sci. Recl. Trav. Chim. Pays-Bas Rocz. Chem. Synthesis Spectrochim. Acta Spectrochim. Acta, Part A S. Afr. Pat. Synth. Commun. Science W. L. F. Armarego, ‘Stereochemistry of Heterocyclic Compounds’, Wiley, New York, 1977, parts 1 and 2. Synlett Synth. Met. Sulfur Reports Supplements to Rodd’s Chemistry of Carbon Compounds Synth. React. Inorg. Metal-Org. Chem. Sch. Sci. Rev. Second Supplements to Rodd’s Chemistry of Carbon Compounds Org. Compd. Sulphur, Selenium, Tellurium [R. Soc. Chem. series] Sulfur Letters Swiss Pat. Tetrahedron Tetrahedron, Suppl. Tetrahedron Asymmetry Talanta Theor. Chim. Acta Top. Curr. Chem. Tetrahedron, Comp. Method Trans. Faraday Soc. Thesis Tetrahedron Lett. Top. Stereochem. Usp. Khim. Ukr. Khim. Zh. (Russ. Ed.) Unpublished Results USSR Pat. U.S. Pat. PCT Int. Appl. WO (World Intellectual Property Organization Pat. Appl.) Yuki Gosei Kagaku Kyokaishi Yakugaku Zasshi Z. Anorg. Allg. Chem. Zh. Anal. Khim. Z. Chem. Z. Naturforsch. Z. Naturforsch., Teil A Z. Naturforsch., Teil B Zh. Obshch. Khim. Zh. Org. Khim. Hoppe-Seyler’s Z. Physiol. Chem. Zh. Prikl. Khim.

List of Abbreviations TECHNIQUES/CONDITIONS 18-C-6 ))))) AAS AES AFM approx. aq. b.p. CD CIDNP CNDO conc. CT ee equiv. ESR EXAFS FVP g GC GLC h h HOMO HPLC h ICR INDO IR l LCAO LUMO MCD MD min MM MO MOCVD m.p. MS

18-crown-6 ultrasonic (sonochemistry) heat, reflux atomic absorption spectroscopy atomic emission spectroscopy atomic force microscopy approximately aqueous boiling point circular dichroism chemically induced dynamic nuclear polarization complete neglect of differential overlap concentrated charge transfer enantiomeric excess equivalent(s) electron spin resonance extended X-ray absorption fine structure flash vacuum pyrolysis gaseous gas chromatography gas–liquid chromatography Planck’s constant hour highest occupied molecular orbital high-performance liquid chromatography light (photochemistry) ion cyclotron resonance incomplete neglect of differential overlap infrared liquid linear combination of atomic orbitals lowest unoccupied molecular orbital magnetic circular dichroism molecular dynamics minute(s) molecular mechanics molecular orbital metal organic chemical vapor deposition melting point mass spectrometry

MW NMR NQR ORD PE ppm rt s SCF SET SN1 SN2 SNi STM TLC UV vol. wt.

molecular weight nuclear magnetic resonance nuclear quadrupole resonance optical rotatory dispersion photoelectron parts per million room temperature solid self-consistent field single electron transfer first-order nucleophilic substitution second-order nucleophilic substitution internal nucleophilic substitution scanning tunneling microscopy thin-layer chromatography ultraviolet volume weight

REAGENTS, SOLVENTS, ETC. Ac acac acam AcO AcOH AIBN Ans Ar ATP 9-BBN 9-BBN-H BEHP BHT binap bipy Bn t-BOC bpy BSA BSTFA Bt BTAF Bz Bzac CAN Cbz chalcogens CH2Cl2 COD COT Cp Cp* 18-crown-6 CSA CSI CTAB DABCO

acetyl CH3COacetylacetonato acetamide acetate acetic acid 2,20 -azobisisobutyronitrile ansyl aryl adenosine 50 -triphosphate 9-borabicyclo[3.3.1]nonyl 9-borabicyclo[3.3.1]nonane bis (2-ethylhexyl) phthalate 2,6-di-t-butyl-4-methylphenol (butyrated hydroxytoluene) 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl 2,20 -bipyridyl benzyl C6H5CH2- (NB avoid confusion with Bz) t-butoxycarbonyl 2,20 -bipyridyl N,O-bis(trimethylsilyl)acetamide N,O-bis(trimethylsilyl)trifluoroacetamide benzotriazole benzyltrimethylammonium fluoride benzoyl C6H5CO- (NB avoid confusion with Bn) benzoylacetone ceric ammonium nitrate carbobenzoxy oxygen, sulfur, selenium, tellurium dichloromethane 1,5-cyclooctadiene cyclooctatetraene cyclopentadienyl pentamethylcyclopentadienyl 1,4,7,10,13,16-hexaoxacyclooctadecane camphorsulfonic acid chlorosulfonyl isocyanate cetyl trimethyl ammonium bromide 1,4-diazabicyclo[2.2.2]octane

DBA DBN DBU DCC DDQ DEAC DEAD DET DHP DIBAL-H diglyme dimsyl Na DIOP DIPT DMA DMAC DMAD DMAP DME DMF DMI DMN DMSO DMTSF DPPB DPPE DPPF DPPP Eþ EADC EDG EDTA EEDQ Et Et2O EtOH EtOAc EWG HMPA HMPT IpcBH2 Ipc2BH KAPA K-selectride LAH LDA LICA LITMP L-selectride LTA MAO MCPBA MCT Me MEM MEM-Cl MeOH MMA MMC MOM

dibenzylideneacetone 1,5-diazabicyclo[4.3.0]non-5-ene 1,5-diazabicyclo[5.4.0]undec-5-ene dicyclohexylcarbodiimide 2,3-dichloro-5,6-dicyano-1,4-benzoquinone diethylaluminum chloride diethyl azodicarboxylate diethyl tartrate (þ or ) dihydropyran diisobutylaluminum hydride diethylene glycol dimethyl ether sodium methylsulfinylmethide 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane diisopropyl tartrate (þ or ) dimethylacetamide dimethylaluminium chloride dimethyl acetylenedicarboxylate 4-dimethylaminopyridine dimethoxyethane dimethylformamide N,N0 -dimethylimidazolidinone diaminomaleonitrile dimethyl sulfoxide dimethyl(methylthio)sulfonium fluoroborate 1,2-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane 1,10 -bis(diphenylphosphino)ferrocene 1,2-bis(diphenylphosphino)propane electrophile ethylaluminium dichloride electron-donating group ethylenediaminetetraacetate N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline ethyl diethyl ether ethanol ethyl acetate electron-withdrawing group hexamethyl phosphoramide hexamethylphosphoric triamide isopinocampheylborane diisopinocampheylborane potassium 3-aminopropylamide potassium tri-s-butylborohydride lithium aluminium hydride lithium diisopropylamide lithium isopropyl cyclohexylamide lithium tetramethyl piperidide lithium tri-s-butyl borohydride lead tetraacetate monoamine oxidase 3-chloroperoxybenzoic acid mercury cadmium telluride methyl methoxyethoxymethyl methoxyethoxymethyl chloride methanol methyl methacrylate methylmagnesium carbonate methoxymethyl

Ms MSA MsCl MVK NBS NCS NMO NMP Nu PPA PCC PDC Ph phen Phth PPE PPO PPTS Pr Pyr Red-Al SDS SEM Sia2BH SM TAS TBAF TBDMS TBDMS-Cl TBDPS TBHP TCE TCNE TEA TES Tf TFA TFAA THF THP TIPBSCl TIPSCl TMEDA TMS TMSCl TMSCN Tol TosMIC TPP Tr Tris Ts TTFA TTMSS TTN X

methanesulfonyl (mesylate) methanesulfonic acid methanesulfonyl chloride methyl vinyl ketone N-bromosuccinimide N-chlorosuccinimide N-methylmorpholine N-oxide N-methyl-2-pyrrolidone nucleophile polyphosphoric acid pyridinium chlorochromate pyridinium dichromate phenyl 1,10-phenanthroline phthaloyl polyphosphate ester 2,5-diphenyloxazole pyridinium p-toluenesulfonate propyl pyridine sodium bis(methoxyethoxy)aluminum dihydride sodium dodecyl sulfate trimethylsilylethoxymethyl disiamylborane starting material tris(diethylamino)sulfonium tetra-n-butylammonium fluoride t-butyldimethylsilyl t-butyldimethylsilyl chloride t-butyldiphenylsilyl t-butyl hydroperoxide 2,2,2-trichloroethanol tetracyanoethylene tetraethylammonium triethylsilyl triflyl (trifluoromethanesulfonyl) trifluoroacetyl trifluoroacetic anhydride tetrahydrofuran tetrahydropyranyl 2,4,6-triisopropylbenzenesulfonyl chloride triisopropylsilyl chloride tetramethylethylenediamine [1,2-bis(dimethylamino)ethane] trimethylsilyl trimethylsilyl chloride trimethylsilyl cyanide tolyl C6H4(CH3)– tosylmethyl isocyanide meso-tetraphenylporphyrin trityl (triphenylmethyl) tris(hydroxymethyl)aminomethane 4-toluenesulfonyl (tosyl) thallium trifluroacetate tris(trimethylsilyl)silane thallium(III) nitrate halogen or leaving group

Volume 6: Synthesis: Carbon With Three or Four Attached Heteroatoms Part I: Tetracoordinated Carbon with Three Attached Heteroatoms RCX 1 X 2 X3 6.01 Trihalides, Pages 1-22, G. Sandford 6.02 Functions Containing Halogens and Any Other Elements, Pages 23-74, J. Suwi ński and K. Walczak 6.03 Functions Containing Three Chalcogens (and No Halogens), Pages 75-110, S. Rádl and S. Voltrová 6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen, Pages 111-159, A. M. Shestopalov 6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 161-203, A. Güven 6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen, or Group 15 Elements; Also the Synthesis of Functions Containing Three Metals, Pages 205-242, V. D. Romanenko and V. L. Rudzevich Part II: Tetracoordinated Carbon with Four Attached Heteroatoms CX1 X 2 X 3 X4 6.07 Functions Containing Four Halogens or Three Halogens and One Other Heteroatom Substituent, Pages 243-269, A. Senning and J. Ø. Madsen 6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents, Pages 271-294, G. Varvounis and N. Karousis 6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents, Pages 295-305, S. V. Yarlagadda and R. Murugan 6.10 Functions Containing Four or Three Chalcogens (and No Halogens), Pages 307-315, A. Senning and J. O. Madsen 6.11 Functions Containing Two or One Chalcogens (and No Halogens), Pages 317-353, W. Petz and F. Weller 6.12 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 355-379, S. Saba and J. A. Ciaccio 6.13 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen, or Group 15 Element; Also Functions Containing Four Metals, Pages 381-408, P. D. Lickiss

Part III: Tricoordinated Carbon with Three Attached Heteroatoms Y=CX1 X 2 6.14 Functions Containing a Carbonyl Group and at Least One Halogen, Pages 409-427, R. Murugan and S. V. Yarlagadda 6.15 Functions Containing a Carbonyl Group and at Least One Chalcogen (but No Halogen), Pages 429-452, H. Eckert 6.16 Functions Containing a Carbonyl Group and Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 453-493, O. V. Denisko 6.17 Functions Containing a Thiocarbonyl Group and at Least One Halogen; Also at Least One Chalcogen and No Halogen, Pages 495-544, E. Kleinpeter 6.18 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 545-572, J. Barluenga, E. Rubio and M. Tomás 6.19 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group— SeC(X 1)X2 and TeC(X1)X2, Pages 573-594, L. J. Guziec and F. S. Guziec, Jr. 6.20 Functions Containing an Iminocarbonyl Group and at Least One Halogen; Also One Chalcogen and No Halogen, Pages 595-604, T. L. Gilchrist 6.21 Functions Containing an Iminocarbonyl Group and Any Elements Other Than a Halogen or Chalcogen, Pages 605-660, F. Sŕczewski ą 6.22 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal, Pages 661-711, V. D. Romanenko and V. L. Rudzevich 6.23 Tricoordinated Stabilized Cations, Anions, and Radicals, +CX1X2X3, - CX1X2X3, and CX1X2X3, Pages 713-727, M. Balasubramanian

.

6.01 Trihalides G. SANDFORD University of Durham, Durham, UK 6.01.1 GENERAL METHODS 6.01.1.1 The Addition of Halogens and Interhalogens to Fluoroalkenes 6.01.1.2 The Addition of Haloalkanes to Haloalkenes 6.01.1.2.1 Lewis acid-catalyzed addition of trihalomethyl cations to haloalkenes—the Prins reaction 6.01.1.2.2 Additions initiated by free radicals, heat, or radiation 6.01.1.2.3 Additions catalyzed by salts and complexes of transition metals 6.01.2 TRIFLUOROMETHYL DERIVATIVES, RCF3 6.01.2.1 General 6.01.2.2 Aryl Derivatives 6.01.2.2.1 Conversion of groups attached to an aromatic ring into the trifluoromethyl group 6.01.2.2.2 Substitution by trifluoromethyl radicals 6.01.2.2.3 Substitution of hydrogen by trifluoromethyl group acting as an electrophile 6.01.2.2.4 Substitution of halogens by trifluoromethyl group acting as a nucleophile 6.01.2.2.5 Substitution of halogen by trifluoromethyl group using derivatives of metals 6.01.2.3 Derivatives of Alkanes, Alkenes, Alkynes, and Other Unsaturated Compounds 6.01.2.3.1 Halogen exchange 6.01.2.3.2 Conversions of other groups to the trifluoromethyl group 6.01.2.3.3 Transfer of trifluoromethyl groups as radicals 6.01.2.3.4 Reactions involving trifluoromethyl derivatives of metals and metalloids 6.01.3 TRICHLOROMETHYL DERIVATIVES, RCCl3 6.01.3.1 Trichloromethyl Groups Attached to an Aliphatic Center 6.01.3.1.1 Conversion of groups attached to an aliphatic center into the trichloromethyl group 6.01.3.1.2 Transfer of the trichloromethyl group to an aliphatic center 6.01.3.2 Trichloromethyl Groups Attached to an Aromatic Ring 6.01.3.2.1 Conversion of groups attached to an aromatic ring into a trichloromethyl group 6.01.3.2.2 Transfer of trichloromethyl group to an aromatic ring 6.01.4 TRIBROMOMETHYL DERIVATIVES, RCBr3 6.01.5 MIXED SYSTEMS WITH FLUORINE, RCF2Hal AND RCFHal2 6.01.6 MIXED HALOFORMS, CHXY2 AND CHXYZ

6.01.1

1 2 2 2 2 4 5 5 5 5 6 6 7 7 8 8 9 10 11 16 16 16 16 17 17 17 17 18 18

GENERAL METHODS

There are several general methods that may be used for the synthesis of trihalomethyl compounds, and these were discussed in detail in COFGT (1995) <1995COFGT(6)1>. The experimental basis behind these established procedures remains valid; so in this chapter, a brief overview of addition reactions of halogens and haloalkenes to alkenes for the synthesis of systems bearing trihalomethyl groups is provided. Recent developments and further applications of these general processes are given where appropriate. 1

2 6.01.1.1

Trihalides The Addition of Halogens and Interhalogens to Fluoroalkenes

The addition of halogens and interhalogens to fluorinated alkenes is a well-established method for the synthesis of compounds bearing CHal3 groups and this area has recently been summarized <2000MI331, 2000MI234>. Many examples of such electrophilic addition processes, involving electrophilic halonium ion and nucleophilic fluoride ion, are given in COFGT (1995) and a few examples (Equations (1)–(3)) are shown below as an illustration <1978JFC(12)257, 1973ZOR673, 1961JCS3779>. CH2=CCl2

HF Hexachloromelamine 33%

CF2 CF CF3

Cl F, –10 °C 100%

CH2Cl CFCl2

CF3–CFCl–CF3

ð2Þ

CF3–CFI–CF3

ð3Þ

IF5, 2 I2

CF2 CF–CF3

ð1Þ

150 °C 99%

6.01.1.2

The Addition of Haloalkanes to Haloalkenes

The addition of haloalkanes to alkenes, catalyzed by either Lewis acids, free radical initiators, salts, and transition metal complexes, may be used for the synthesis of systems that bear trihalomethyl substituents, following the general scheme shown in Equation (4).

CY3–X +

6.01.1.2.1

CY3

X = Hal or H Y = Hal

X

ð4Þ

Lewis acid-catalyzed addition of trihalomethyl cations to haloalkenes—the Prins reaction

Trihalomethylation of alkenes by Lewis acid-catalyzed condensation with a tetrahalomethane, an adaptation of the Prins reaction, has been known for many years <1977FCR39>. Representative examples <1974CCC1330, 1971CCC1867> to illustrate these processes are shown below (Equations (5) and (6)), although this methodology has undergone limited recent development. F

H + CFCl3

F

F

F

0 °C, 7 h 65%

CF3

F CCl3

+

CF2Cl

CFCl2

ð5Þ

(70:30) F

F + CHFCl2

F

F

15 °C, 3 h 58%

F CF3

F

F

CHCl2

+

CF2Cl

F CHFCl

ð6Þ

(59:41)

6.01.1.2.2

Additions initiated by free radicals, heat, or radiation

Trihalomethyl radicals, generated by heat, peroxide, or UV initiation, react with alkenes to form an intermediate radical as shown below (Scheme 1). This radical may then react with further equivalent(s) of alkene to lead to oligomers and polymers or abstract a halogen atom from a molecule of the starting material to give a tetrahalogenated product.

3

Trihalides Initiation hν or heat

CY3 X or

RO–OR RO

CY3 +

X

2 RO

+ CY3 X

RO-X + CY3

+

Y3C

Propagation CY3 Chain transfer Y 3C

+ CY3–X

Y3C

X

Kharasch addition product

Oligomerization Y3C

n

+

Y 3C n

Termination + CY3–X

Y3C

Y3C

X

n

n

oligomers (n = 2–20) polymers (n = >20)

Scheme 1

The product distribution depends upon the relative rates of each of the stages outlined above. Generally, starting materials with weak carbonhalogen bonds (iodides) give predominantly lowmolecular-weight products, whilst systems with relatively strong carbonhalogen bonds give a higher proportion of oligomeric products. Furthermore, if the alkene is not easily polymerized under normal conditions (e.g., hexafluoropropene) the addition product is favored, while readily homopolymerized alkenes lead to polymeric systems. The addition of the halomethyl radicals is often regioselective due to a combination of steric and electronic factors <1982AG(E)401, 1996CRV1557, 1997TCC(192)97>. Since the initial report by Kharasch <1947JA1100> describing such radical chain addition processes, a substantial literature has developed <1963OR91, B-1992MI002, B-1986MI001>, detailing the syntheses of a great number of free-radical addition adducts, oligomers, and polymers all bearing trihalomethyl end groups. A selection of these processes is given below (Equations (7)–(11)) to illustrate some of the processes possible <1961JOC2089, 1955JA2783, 1953JCS1592, 1964JOC1198, 1981TL3405>.

OH + CF3I

F

+ CBr2F2

Cl

F

F

F

I

hν

F3C

50%

OH

Br

(PhCO)2O 100 °C 32%

+ CF3I

OEt + CBr2F2

F

Br F

F

hν 75%

hν 83%

F

F

I

F CF3

Cl

F F

Br

Br

ð7Þ

ð8Þ

ð9Þ

ð10Þ OEt

4

Trihalides

O

N + CF2BrCl

ð11Þ

CF2Cl

rt H2O 65%

The addition processes outlined above all lead to the formation of tetrahaloalkane systems in which trihalomethyl and halogen are added across a double bond. These reactions have, however, recently been adapted for the synthesis of trichloromethyl derivatives by the addition of an effective hydrogen atom donor (Equations (12) and (13)). Reaction of tetrachloromethane with alkenes in the presence of diethyl phosphite leads to good yields of trichloromethylated products because hydrogen is transferred to the intermediate radical, rather than halogen abstraction occurring <2001SL1719>. Cl (EtO)2P(O)H

+ CCl4

C6H13

(PhCO2)2

CCl3

C6H13

+

(55%)

OH

+ CCl4

(EtO)2P(O)H (PhCO2)2

CCl3

CCl3

C6H13

ð12Þ

(30%)

OH

+

CCl3

OH

ð13Þ

(44%)

(16%)

This methodology has been adapted to allow free-radical tandem trichloromethylation/cyclization processes (Equation (14)) which occur efficiently in the presence of diethyl phosphite <2001TL3137>.

CCl4, (EtO)2P(O)H

Cl3C

Cl

+

(PhCO2)2O Dioxane

N Tos

6.01.1.2.3

Cl3C N Tos

N Tos

(60%)

(4%)

ð14Þ

Additions catalyzed by salts and complexes of transition metals

The observation that thermally initiated addition processes involving reaction between carbon tetrachloride and acrylonitrile could be affected by the presence of metals or metal salts to give greater yields of the Kharasch addition product rather than oligomers prompted much research. Many different metals, metal salts, metal oxides, and transition metal complexes have been assessed for their effectiveness in such addition processes and are listed in COFGT (1995). Recently, Kharasch addition using ruthenium(II) complexes has been assessed <2000TL5347> and the process (Equation (15)) may be affected by changing the ligand on the ruthenium metal center <2000TL6071>. Cl O OMe

+ CCl4

RuCl(Cp*)(PPh3)2 40 °C

Cl3C

O

ð15Þ

OMe

Grubbs’ well-defined ruthenium catalyst, RuCl2(¼CHPh) (PR3)2 <1999JOC344>, and various diaminonickel (II) ‘‘pincer’’ complexes <1998ACR423> have also been used to promote both addition and polymerization reactions.

5

Trihalides 6.01.2

TRIFLUOROMETHYL DERIVATIVES, RCF3

6.01.2.1

General

The growing number of life science products that bear trifluoromethyl groups provides a continuing driving force for the development of effective methodology that enables both regio- and stereoselective introduction of trifluoromethyl groups into both aliphatic and aromatic systems. In more specific cases, the use of -trifluoromethyl ketones as potent enzyme inhibitors <2001MI755> and the synthesis of aliphatic cyclic systems that bear trifluoromethyl groups has been discussed <2000T3635>. In general, trifluoromethylating reagents which transfer trifluoromethyl groups directly onto a substrate by carboncarbon bond formation may be considered as either electrophilic (CF+ 3 ), radical (CF_3), or nucleophilic (CF3) trifluoromethylating systems. It is fair to say that in the 1990s many of the major developments in this area of synthetic chemistry have occurred in nucleophilic trifluoromethylation methodology, particularly in the use of Ruppert’s reagent, CF3SiMe3. This is reflected in the publication of major reviews detailing syntheses involving Ruppert’s reagent by Prakash <1997CRV757, 2001JFC(112)123> and Shreeve <2000T7613>, and more general nucleophilic trifluoromethylation by Langlois <2003S185>. Of course, functional group interconversion, resulting in the transformation of substituents, already located on a substrate, into a trifluoromethyl group upon reaction with a fluorinating reagent (carbonfluorine bond formation), is an alternative strategy.

6.01.2.2 6.01.2.2.1

Aryl Derivatives Conversion of groups attached to an aromatic ring into the trifluoromethyl group

Reaction of trichloromethyl and carboxylic acid groups with fluorinating agents, as discussed in COFGT (1995), continues to provide effective methodology for the synthesis of trifluoromethyl aromatic derivatives. Recent adaptations of this methodology are outlined below. Exchange of halogen for fluorine (Halex process) involving reaction of benzotrichloride derivatives with anhydrous hydrogen fluoride, antimony trifluoride, or hydrogen fluoride/antimony pentafluoride as fluorinating agents remains the most useful industrial process for the synthesis of aromatic trifluoromethyl derivatives. A one-step Friedel Crafts/Halex process is particularly efficient for the synthesis of various brominated <1981JFC(18)281> and acetanilide <2003TL1747> trifluoromethyl derivatives (Equations (16) and (17)). Br

CF3

CF3 Br

HF, CCl4

ð16Þ

+ Br

H

N

H

Ac

N

i. HF, CCl4 , SbF5 ii. HF.pyridine Cl

85%

Ac

ð17Þ CF3 Cl

There are now many examples of the transformation of carboxylic acid groups into trifluoromethyl groups using sulfur tetrafluoride, and this methodology continues to be used for the synthesis of poly trifluoromethyl aromatic systems <1997JFC(82)163> (Equation (18)). HO2C

CO2H CO2H

i. HF, SF4 ii. KOH 55%

F3C

CO2H CF3

ð18Þ

6 6.01.2.2.2

Trihalides Substitution by trifluoromethyl radicals

Electrophilic trifluoromethyl radicals, generated by electrolysis of potassium trifluoromethanesulfinate (Equation (19)) may be trapped by electron-rich aromatic systems <2002SL1697> (Equation (20)). –e–

CF3SO2

CF3SO2

–SO 2 OMe

OMe

CF3

CF3SO2K, DMF Et4NClO4 Electrolysis 32%

OMe

6.01.2.2.3

ð19Þ

CF3

ð20Þ OMe

Substitution of hydrogen by trifluoromethyl group acting as an electrophile

For electrophilic trifluoromethylating reagents, originally developed by Umemoto, the trifluoromethyl group is made highly susceptible toward nucleophilic attack by being attached to a very good leaving group, such as a sulfonium derivative (Equation (21)). +

Nuc

ð21Þ

Nuc CF3 + SR2

CF3 SR2

Intramolecular cyclization of trifluoromethyl sulfoxides provides efficient methodology for the synthesis of trifluoromethyl dibenzothiophenium salts (Equation (22)), which act as effective electrophilic trifluoromethylating reagents that are now commercially available but expensive <1998JFC(92)181, 1999JFC(98)75>.

60% SO3–H2SO4

NaOTf S CF3

S CF3 O

HSO4

S CF3

MeCN 92%

ð22Þ OTf

Variation of the chalcogen (S, Se, Te) and aromatic ring substituents lead to a series of related sulfur, selenium, and tellurium (trifluoromethyl)dibenzo-phenium triflates that can act as ‘‘power variable’’ trifluoromethylating reagents, in which the most powerful trifluoromethylating reagents are based on sulfonium systems with highly electron-withdrawing groups attached to both aromatic rings <1995JFC(74)77>. Electrophilic trifluoromethylation of anilines <1995JFC(74)77> (Equation (23)), for which related kinetic studies have been performed <1996JFC(80)163>, and zinc porphyrins <1999EJO2471>, which leads to the synthesis of longer-wavelength absorbing meso-substituted systems (Equation (24)), has been reported using the Umemoto reagents.

NH2

SO3

NO2

NH2

NH2

S+ CF3

CF3

ð23Þ

+ CF3 (18%)

(37%)

N

N Zn

N

CF3 S+

N

O2N

NO2 CF SO 3 3

N

N Zn

N

CF3 N

THF 16%

+ three other products

ð24Þ

7

Trihalides

New electrophilic trifluoromethylating reagents, based upon diaryl sulfides (Equation (25)), allow efficient trifluoromethylation of pyrroles <1998JOC2656>. O S

CF3

Benzene Tf2O

HNO3

OTf

S+ CF3

OTf NO2

S+ CF3

80%

N H

6.01.2.2.4

ð25Þ

N H

CF3

Substitution of halogens by trifluoromethyl group acting as a nucleophile

Only aromatic systems that are highly activated toward nucleophilic attack may be trifluoromethylated directly by nucleophilic aromatic substitution using trifluoromethyl anions generated by reaction of fluoride ion with Ruppert’s reagent <1990IZV169> (Equation (26)). CF3

F F

F

F

6.01.2.2.5

N

F

TMS–CF3 TAS–F

F

F

F

N

ð26Þ

F

Substitution of halogen by trifluoromethyl group using derivatives of metals

Trifluoromethylcopper, which may be generated in situ by various methods <1986JA832> including from either trifluoromethyl iodide and copper or sodium trifluoroacetate and copper(I) iodide, acts as a source of trifluoromethyl anion for the replacement of bromine and iodine, activated toward nucleophilic attack by the presence of copper ions, attached to activated aromatic rings. Syntheses of trifluoromethyl retinoial analogs <1999JFC(96)159> (Equation (27)), aromatics <2002T121, 1999JFC(96)159> (Equation (28)), and pyridine derivatives <2002EJO327> (Equations (29) and (30)) have been reported recently using these reagent systems. OMe

OMe O

Ph

O

CF3COONa CuI, DMF 84%

Br OMe Br

OMe CF3

ð28Þ

CuI

NO2

85% Br

TMSCF3 N

I

ð27Þ

CF3

FSO2CF2CO2Me

NO2

Ph

Br

KF, CuI

N

CF3

ð29Þ

69% I N

Cl

CF3

TMSCF3 KF, CuI 67%

ð30Þ N

Cl

8

Trihalides

6.01.2.3

Derivatives of Alkanes, Alkenes, Alkynes, and Other Unsaturated Compounds

Many of the reagents utilized for trifluoromethylation of aromatic systems have been applied to corresponding trifluoromethylation of aliphatic derivatives at both sp2 and sp3 carbon sites.

6.01.2.3.1

Halogen exchange

Halogen exchange (halex) processes, involving nucleophilic substitution of halogen by fluorine using a metal fluoride in combination with anhydrous hydrogen fluoride, continues to be very important for the industrial production of small fluorinated hydrocarbons such as the chlorofluorocarbons (CFCs) and hydrofluorocarbons (HFCs). Since the establishment of the Montreal Protocol, effectively banning the use of CFCs in developed countries, manufacturing processes for the synthesis of HFCs have been rapidly implemented. Metal fluoride-effected substitution processes proceed via carbocation intermediates, (Scheme 2), as explained more fully in COFGT (1995). C Cl + MFx

C

HF

MFx–1Cl

C F

or C

Cl F

MFx–1

Scheme 2

Representative examples of this established and very important methodology are reiterated below for completeness (Equations (31) and (32)). Metal fluorides such as antimony pentafluoride and various chromia catalysts are most commonly used in conjunction with HF <1942JA3476, 1960USP2921099>. Cl

CCl3

Cl Br

SbF3, SbF3Cl2

Cl

ð31Þ

CF3

80%

Cl

Br

Cl H

F3C

HF, SbF3 42%

Br

Cl H

ð32Þ

Fluorinated chromia aerogel materials <2003JFC(121)83> (Equation (33)), alumina and aluminum(III) fluoride <2001JFC(110)181, 2001JFC(107)45>, and chromia impregnated with zinc <1999GC9> act as heterogeneous catalysts for the isomerization of various CFCs. CCl2F–CF2Cl

Chromia catalyst

ð33Þ

CF3–CCl3

Heat

The manufacture and current applications of HFCs and the current market situation regarding HFCs have been discussed <2001CI(M)83> and the process of phasing out CFCs has been addressed <2002JFC(114)237>. Various halogen exchange processes have been performed in which most, or all, of the usual aprotic solvent medium, such as sulfolane, was replaced by a perfluoroalkane fluid. In some cases, the products obtained using sulfolane/perfluoroalkane media were different from those found when using sulfolane alone. Hexachlorodiene, for example, gave hexafluorobut-2-yne, rather than heptafluorobutene, as the major product (Equation (34)) when carried out in a perfluoroalkanerich reaction medium because elimination of fluoride to give the alkyne occurs preferentially <1997JCS(P1)3623>. Cl

Cl Cl

Cl

KF, 190 °C Sulfolane, PFPHP

Cl

CF3

CF3

+

CF3

(75%)

ð34Þ

Via carbanion:

F

Cl

CF3

H CF3

(25%)

F

CF3

9

Trihalides 6.01.2.3.2

Conversions of other groups to the trifluoromethyl group

Bromine trifluoride, prepared from fluorine and bromine, converts aliphatic nitriles to the corresponding trifluoromethyl derivatives (Equation (35)) by a sequence of addition/elimination processes <2001JFC(111)161>. NC

CF3

CO2Et

CO2Et

BrF3

ð35Þ

35%

Fluorodesulfurization of unsaturated dithiolates (Equation (36)) mediated by sources of positively charged halonium and negative fluoride ion, give rise to various trifluoromethyl alkenes <1996SL1199>. S Ar

NIS Bu4NH2F3

SEt

CF3

Ar

ð36Þ

65%

Trifluoromethyl 1,3-diketone systems may be synthesized upon reaction of an electrophilic trifluoromethylation reagent with the corresponding carbanion precursor <1995JFC(74)77>, giving overall substitution of hydrogen by trifluoromethyl (Equation (37)). CH3 Na

O

O

A, DMF

CH3 O

CF3 A=

O

SO3

ð37Þ

S CF3

86%

Perfluorinated systems, that is, molecules in which all the hydrogen atoms have been replaced by fluorine, may be synthesized by a variety of techniques. Direct fluorination (Equations (38)–(40)) permits the synthesis of perfluorinated systems from the parent hydrocarbons <1979MI161, 1997TCC(193)1, 2003T437>. The concentration of fluorine and the reaction temperature are slowly increased over a period of several days to effect perfluorination, while minimizing substrate degradation. Many perfluorinated systems bearing trifluoromethyl groups have been synthesized by this technique and some examples are given <1997TCC(193)1> (Equations (38)–(40)). F2, N2 89%

CF3 CF3

CF3 F

CF3 F CFCF3 3

F

CH3

F

ð38Þ

CF3 F2, N2

F CH3

CF3

O

F

26%

F

ð39Þ

CF2CF3

ð40Þ

CF3

F

F2, N2, NaF hν

CF3

O

85%

Perfluorination of hydrocarbons by cobalt trifluoride continues to be used for the manufacture of a range of perfluorinated fluids. In particular, perfluorination of methyl-substituted aromatic substrates (Equation (41)) is very useful for the synthesis of trifluoromethylated perfluoroalkanes <1960AFC166>. CF3 CoF3, 360 °C 77%

ð41Þ F

10

Trihalides

Electrolysis of an organic substrate, dissolved in anhydrous hydrogen fluoride gives the corresponding perfluorinated derivatives by electrochemical fluorination (ECF). Starting materials that are soluble in HF are the most readily fluorinated and many perfluorinated amines (Equation (42)) and ethers have been efficiently synthesized by this methodology <1997TCC(193)197, 1988JFC(38)303>. HF, electrolysis

F

N

F

N

ð42Þ

CF3

6.01.2.3.3

Transfer of trifluoromethyl groups as radicals

Trifluoromethyl radicals may be generated from electrolysis or radiolysis of trifluoroacetic acid or related salts or thioesters or by homolytic cleavage of the weak carbonbromine bond in trifluoromethyl bromide. Irradiation of trifluoromethylthioacetates or trifluoromethane thiosulfonates gives trifluoromethyl radicals that react regioselectively with electron-rich alkenes at the least hindered site (Equation (43)). However, some reduction of the thiophenyl group is also obtained, leading to a mixture of products <2000TL3069>.

CF3–SO2–SPh +

SPh

hν , 40 °C

C9H19

+

CH2Cl2

C9H19

CF3

CF3

C9H19

ð43Þ

33%

49%

Trifluoromethyl radicals, generated by electrolysis of potassium trifluoromethane sulfinate, may be trapped by electron-rich alkenes and aromatic systems (Equation (44)) <2002SL1697>. C9H19

CF3SO2K, DMF

CF3

CF3

Et4NClO4 Electrolysis

CF3

ð44Þ

(69%), ratio 78:12:10

Radical trifluoromethylation, followed by nucleophilic cyclization in a tandem process (Equation (45)) gives rise to various trifluoromethyl carbohydrate derivatives <1998JFC(91)179>. S

O

CF3Br, HCO2Na

O

S HO

F3C S S O

NaHCO3, SO2

O

72%

H O O H

ð45Þ

O

Electrochemical trifluoromethylation of 3-sulfolene (Equation (46)) <1998JFC(87)179> and dimethyl acetylenedicarboxylate <1996JFC(78)193> in a trifluoroacetic acid/aqueous acetonitrile medium gives mixtures of products. However, radical addition of trifluoromethyl groups, followed by coupling of the intermediate radical derivatives, provides access to various bis-trifluoromethylated systems (Equation (47)) <1997T4437>.

S O

O

MeCN, H2O Electrolysis CN

CF3

CF3 CF3

CF3 CF3COOH

+ Six other products

+ O

O

O

MeCN, H2O Electrolysis

O CN

CF3COOH

25%

ð46Þ

S

S

CF3

CF3 CN

ð47Þ

11

Trihalides 6.01.2.3.4

Reactions involving trifluoromethyl derivatives of metals and metalloids

Trifluoromethyltrimethylsilane, CF3TMS, commonly referred to as Ruppert’s reagent <1984TL2195> and now commercially available, was first used for trifluoromethylation of carbonyl derivatives (Equation (48)) in 1989 by Prakash and co-workers <1989JA393>: O

CF3 OH Me3SiCF3

ð48Þ

TBAF 77%

Efficient trifluoromethylation occurs in the presence of a source of fluoride ion, such as caesium fluoride, TBAF, TBAT, or amberlite-fluoride resin <2002MI197> whereby fluoride ion attacks the silicon atom to release trifluoromethyl anions that are subsequently trapped by an electrophilic carbon site (Scheme 3): O R1

+ CF3 SiMe3

R2

Bu4 N

+

F

–

SiMe 3 F CF3

O – Bu4 N

R1

R2

+

CF3 SiMe 3

CF3 Me Si Me Me CF3 O R1

CF3

OSiMe3

R1

R2

H

+

CF3

OH

R1

R2

O

–

Bu4 N

R1

+

R2

R2

Scheme 3

Since the initial reports, the use of TMSCF3 for trifluoromethylation has been reviewed extensively <1997CRV757, 2000T7613, 2001JFC(112)123> and only representative examples of the large body of work that has been published are outlined here. Effective trifluoromethylation of many carbonyl containing systems, such as aldehydes (Equation (49)) <1998JFC(88)79>, ketones (Equation (50)) <1998TA213>, esters, ,-unsaturated ketones (Equations (51) and (52)) <2000JFC(101)199, 2000OL3173>, -keto esters (Equation (53)) <2000OL3173, 1991SL643>, and lactones (Equation (54)) <1993TL8241> have been described. O

O

N H Boc

Me3SiCF3 TBAF

N Boc

O O

ð49Þ

O O O

O

CF3 OH H

O

O

Me3SiCF3 O O

TBAF

O

HO

HO CF3

ð50Þ O O

CF3

CF3

i. TMSCF3, TBAF (cat.)

PCC

ii. TBAF (1 equiv.)

H2SO4

ð51Þ O

12

Trihalides H

CF3

i. TMSCF 3, CsF (cat.)

Ph

O

OH (90%)

Ph

ii. conc. HCl

i. O3, –78 °C ii. Me2S R1

R2

N

F3C

R1R2NH R3-B(OH)2

R3

OH H

OH

CF3 O

O

CF3 OH O

Me3SiCF3

O

TBAF 83%

O O

O

ð52Þ

O

ð53Þ

O

Me3SiCF3

OH

O

O

CF3

TBAF

O

ð54Þ

O

In attempts to synthesize enantiopure trifluoromethyl alcohols, chiral triaminosulfonium salts gave modestly enantioselective catalytic additions to carbonyl systems (Equation (55)) <1999TL8231, 2000MI1037>. OH * Ph CF3

Chiral catalyst 96%

PhCHO + TMS-CF3

52% ee

ð55Þ

Ph

Chiral catalyst =

Ph3SnF2

N S 3

Ph

Reaction of Ruppert’s reagent with methyl esters can lead to replacement of the methoxy group to furnish -trifluoromethyl ketones (Equation (56)) <1998AG(E)820, 1999JOC2873>: O

O OMe

O2N

TMSCF3 TBAF 81%

CF3

ð56Þ

O2N

In contrast, nucleophilic substitution of halides by trifluoromethyl anion is very difficult and only very highly reactive perfluoroalkenes (Equation (57)) <1993IC4802> and acid fluorides (Equation (58)) <1993IC5079> may be functionalized in this manner. CF3 N=CF 2

CF3

TMS–CF3 KF

CF3

N

CF3

ð57Þ

68% O

O

F F F

F F F

O

TMS–CF3 KF

F F CF3

CF3 F F

ð58Þ

O

Trifluoromethylation of ketones followed by Ritter reaction using acetonitrile in strong acid leads to a variety of trifluoromethylated amides in a one-pot procedure (Equations (59) and (60)) <1997SL1193>. O O Ph

TMS–CF3, TBAF (cat.) Ph

CH3CN, H2SO4 68%

H Ph

N Ph CF3

ð59Þ

13

Trihalides O

CF3 TMS–CF3, TBAF (cat.)

O

CH3CN, H2SO4 54%

ð60Þ

N H

Efficient trifluoromethylation of imines (Equation (61)) <1999TL5475> and other related systems including ,-unsaturated sulfonaldimines (Equation (62)) <2001SL77>, chiral sulfinimines (Equation (63)) <2001AG(E)589>, and azirines (Equation (64)) <1994TL3303>, in which the carbonnitrogen double bond is attacked by trifluoromethyl anion, has been established, giving various trifluoromethylated amine derivatives. In particular, stereoselective addition of trifluoromethyl groups to imines is possible in systems that possess chiral sulfoxide moieties adjacent to the carbonnitrogen double bond <2001AG(E)589>. R3 R1

N

R1 R2

i. TMSCF 3, TMS-imidazole, CsF, THF R2 ii. SiO2, 2 M HCl

N

SO2tol

TMSCF3 TBAT 87%

Cl

t-Bu

H N

N R3

H

ð61Þ

CF3

H

O S

CF3

TMSCF3

t-Bu

O S

N H

Cl

CF3 HCl, MeOH

N H

85%

97:3 diastereomers

Ph N

R1 R2

ð62Þ

CF3

TBAT

O

SO2tol

TMSCF3 TBAF

H3N

O

O

ð63Þ

Cl

Ph F3C

R1 R2

N SiMe3

ð64Þ

Nucleophilic trifluoromethylation by germanium reagents, which are analogous to the trimethylsilyl systems described above, also trifluoromethylate C¼N double bonds (Equation (65)) <1997TL3443, 1996SL1191>.

Ph

N

Ph

C6H5SCF3 Et3GeNa HMPA 96%

CF3 Ph

N H

Ph

ð65Þ

Whilst the use of Ruppert’s reagent is becoming widespread, the development of other sources of trifluoromethyl anion continues. Successful application of fluoroform (Equation (66)) <1998TL2973, 1999T275> and hemiaminals of fluoral, derived from either DMF <2000JOC8848, 2000TL8777> or morpholine (Equation (67)) <2000OL2101>, for analogous trifluoromethylations of ketones has been discussed by Langlois <2003S185, 2001EJO1467>.

O Ph

HCF3, ButOK H

DMF

CF3 OH Ph

H

ð66Þ

14

Trihalides CF3 N

O

OTMS +

O

R1

CF3 OTMS

TBAF

R1

R2

ð67Þ

R2

Addition of N,N-dimethyltrimethylsilylamine to trifluoroacetophenone gives a stable nucleophilic trifluoromethylating reagent (Equation (68)) that reacts with carbonyl derivatives upon catalysis by caesium fluoride <2002SL646>. Related reagents may also be derived from various trifluoromethylamides (Equations (69) and (70)) <2003SL230, 2003AG(E)3133> and sulfinates (Equation (71)) <2003SL233>: O O Ph

110 °C

CF3 + Me2N–SiMe3

Me2N

OTMS

Ph

R1

CF3

R2

HO

CF3

R1

R2

CSF

ð68Þ

O O CF3

N

+ Ph

N

Ph

ButOK

HO

CF3

DMF, THF

Ph

Ph

Bn

ð69Þ

100%

Ph O

Ph Me3SiO O

N

+

Ph

H

CF3

O Ot Bu

+ Ph N

Ph

ii. Bu 4NF 89%

CF3 O S

OH

i. CsF

ButOK

HO

THF

Ph

CF3

CF3

ð70Þ

ð71Þ

N

91%

A further nucleophilic trifluoromethylating reagent may be generated by a single-electron transfer process from the highly electron-rich alkene, tetrakis(dimethylamino)ethylene, to trifluoromethyl iodide. A complex between the TDAE dication and trifluoromethyl anion is thought to be the active reagent which may be used to synthesize -trifluoromethyl alcohols (Equation (72)) <2001OL4271>, trifluoromethyl alcohols (Equation (73)) <2002OL4671> and give bis-trifluoromethylation of acid halides, proceeding via the trifluoromethyl ketone (Equation (74)) <2002TL4317>: O O

S

O

Me2N

O

NMe2

THF

NMe2

55%

+ CF3I + Me2N

HO

CF3

ð72Þ

TDAE O Ph

H

+ CF3I + TDAE

DMF

HO

CF3

78%

Ph

H

ð73Þ

O O Ph

Cl

+ CF3I + TDAE

O

Et2O 98%

Ph

Ph

ð74Þ

CF3 CF3

A combination of an electron-rich phosphene and trifluoromethyl bromide may add to amides which are activated by a Lewis acid. Dehydration results in the formation of trifluoromethyl enamines (Equation (75)) <1995JFC(70)89>: O CH3

N CH3

P(NEt2)3, CF3Br CH3

BCl3 25%

CF3 CH3

N CH3

H H

ð75Þ

15

Trihalides

Trifluoromethylcopper may be generated from a variety of sources including reaction of either CF3I, CF3Br, or trifluoromethanesulfonyl chloride with copper powder in aprotic solvents or from sodium trifluoroacetate and copper(I) iodide <1995COFGT(6)1>. This trifluoromethylating reagent generated in situ is effective for the replacement of halogens attached to aromatic ring systems and also useful for the stereoselective transformation of haloalkenes into trifluoromethyl alkenes (Equations (76)–(78)) <1995JFC(72)241, 2001TL5929, 2001JFC(108)79, 2002JOC9421> such as in steroidal alkenyl bromides <1998JCS(P1)1139>.

NO2

CO2Et

NO2

FSO2CF2CO2Me

CO2Et 24/1 (E )/(Z )

CuI, DMF

Br

ð76Þ

CF3

91%

CO2Et

CO2Et FSO2CF2CO2Me

I O

O

O

F Ph

9/1 (Z )/(E )

CuI, DMF 81%

NaF, diglyme 82%

O

F

F

F

FSO2CF2CO2Me

FSO2CF2CO2Me

I

ð77Þ

CF3

Ph

ð78Þ

CuI, DMF

I

Ph

CF3

45%

Stereo- and regioselective replacement of terminal iodine atoms in 1,2-diiodoalkenes occurs upon treatment with trifluoromethylcopper. An excess of the trifluoromethylation system allows the synthesis of ditrifluoromethyl alkenes from di-iodoalkene precursors (Equations (79)–(81)) <1998JOC9486>:

I Ph

I

I

Ph

CuI, DMF 90%

Ph

I

CuI, DMF 88%

MeO2C

2.5 equiv. FSO2CF2CO2Me CuI, DMF

I

ð79Þ

CF3

I

FSO2CF2CO2Me

MeO2C

I

I

FSO2CF2CO2Me

ð80Þ

CF3

F3C Ph

ð81Þ

CF3

91%

Similar processes are effective in the presence of a palladium species which catalyzes insertion of trifluoromethyl group into carbonhalogen bonds (Equation (82)) <2001JFC(111)185>:

Br NO2

Br

CF3

FSO2CF2CO2Me CuI, Pd(PPh3)4 82%

NO2

CF3

ð82Þ

16

Trihalides

Allyl iodides are displaced by trifluoromethyl upon reaction with chlorodifluoroacetate and fluoride ion in the presence of copper(I) iodide (Equation (83)). The process probably occurs via carbene type mechanism, although this is not clear <1998TL3961>.

MeSO2

6.01.3

I

ClCF2CO2Me KF, CuI, DMF 43%

MeSO2

CF3

ð83Þ

TRICHLOROMETHYL DERIVATIVES, RCCl3

6.01.3.1 6.01.3.1.1

Trichloromethyl Groups Attached to an Aliphatic Center Conversion of groups attached to an aliphatic center into the trichloromethyl group

The most direct and industrially important method of introducing trichloromethyl groups into an aliphatic system remains sequential chlorination, in the presence of a Lewis acid, followed by dehydrochlorination (Equation (84)). Cl

6.01.3.1.2

Cl

Cl2

Cl

Cl

–HCl Cl

Cl

HCl Cl

Cl Cl

ð84Þ

Transfer of the trichloromethyl group to an aliphatic center

Trichloromethyl anions may be generated from chloroform/BuLi, chloroform/NaOH, or TMSCCl3/base, and react with various organic substrates that possess electrophilic carbon sites. However, trichloromethyl anion is relatively unstable and must be generated at low temperature (100 C) before loss of chloride ion, giving reactive dichlorocarbene, occurs as a competing process leading to the formation of unwanted side products. Nevertheless, some useful syntheses utilizing trichloromethyl anions have been developed. Michael-type addition processes (Equations (85) and (86)) to a range of electron-poor alkenes occur to give corresponding trichloromethyl adducts <1993JOC267, 1999OL2165> and -trichloromethyl alkanes may be prepared by reaction with sufficiently activated haloalkanes (Equation (87)) <1990JOC1281>. O

O OEt

O

TMSCl 75%

Et

I

OEt

ð85Þ

PPh3

O

CHCl3, BuLi

S N O

O

Cl3C

THF 90%

PPh3

O

O

CHCl3, BuLi

CCl3

S N O 55:45 ratio of diastereoisomers

ð86Þ

O

CHCl3, BuLi HMPA 68%

Et

CCl3

ð87Þ

Chloroform may be deprotonated by aqueous sodium hydroxide in the presence of a quaternary ammonium salt to give trichloromethyl anion which exists in equilibrium with dichlorocarbene. In general, for this reagent system, electron-rich alkenes react with dichlorocarbene, whereas electron-poor alkenes react by conjugate addition (Equation (88)). The reaction outcome is sensitive toward the type of ammonium salt present as the phase-transfer catalyst <1997T1053>. Lipophilic salts are more effective at promoting conjugate addition, rather than competing cyclopropanation involving dichlorocarbene addition. Indeed, catalysts may be

17

Trihalides

designed so that only products arising from Michael addition are obtained, providing a potentially useful solution to the problem of competing dichlorocarbene reactions <1999T6329, 2003PJC709>.

OCOPh

Cl

+

PTC

OCOPh

PTC = Me4NHSO4 BnEt3NCl

6.01.3.2

Cl

CCl3

CHCl3, 50% aq. NaOH

OCOPh 68% —

5% 65%

ð88Þ

Trichloromethyl Groups Attached to an Aromatic Ring

6.01.3.2.1

Conversion of groups attached to an aromatic ring into a trichloromethyl group

Free-radical chlorination, initiated by either heat or radiation, of methyl groups attached to aromatic and heteroaromatic rings bearing a range of functionalities are well established (Equation (89)), as discussed in COFGT (1995). Alternative methodologies to these industrially operated processes have not been generally developed:

CCl3

Cl2

ð89Þ

Heat or hν

6.01.3.2.2

Transfer of trichloromethyl group to an aromatic ring

Aromatic systems may be trichloromethylated by reaction with carbon tetrachloride and a Lewis acid, usually aluminum trichloride, by Friedel–Crafts process. Trichloromethyl derivatives are the major products but further Friedel–Crafts reaction of this system may take place to yield the corresponding diaryldichloromethane (Equation (90)) <1987JPR1131>. Carbocation rearrangements may occur in the highly acidic reaction medium, for example, durene gives exclusively a product arising from acid catalyzed rearrangement (Equation (91)) <1960JA4460>. Acid catalyzed oligomerization of 2,4-disubstituted thiophenes occurs upon reaction with the carbon tetrachloride/aluminum trichloride reagent system <1998CHE1276>.

Cl

CCl3

CCl4, AlCl3

CCl4, AlCl3

6.01.4

Cl

ð90Þ

+

CCl3

ð91Þ

TRIBROMOMETHYL DERIVATIVES, RCBr3

Methodologies for the synthesis of tribromomethylated derivatives are analogous to processes useful for the preparation of corresponding trichloromethyl systems. Tribromomethyl anions, generated from either decarboxylation of tribromoacetic acid <1967JOC2166> or tributyl (tribromomethyl)stannane <1975JOM(102)423>, react with electrophilic carbon centers, although development of this methodology remains very limited.

18 6.01.5

Trihalides MIXED SYSTEMS WITH FLUORINE, RCF2Hal AND RCFHal2

Many systems bearing CF2Hal and CFHal2 groups are synthesized as by-products of the various halex reactions described above. Other more general syntheses, involving either displacement of fluorine or the transfer of such groups onto organic substrates, are noted below. Transformation of -trifluoromethyl ketones to corresponding difluorohalo derivatives can be accomplished in two steps (Equations (92) and (93)) involving halogenation of the trimethylsilyl enol derivative of the starting ketone <2003JFC(121)239>. O Mg, TMS–Cl

CF3

THF

Cl

F

Cl

O

THF

F3C

F

F3C

I2 60%

OSiMe3 F

Mg, TMS–Cl

CF3

O

OSiMe3 F

CF2I

ð92Þ

CF2Br

ð93Þ

Cl O

Br2 87%

F3C

Various difluorobromo- and difluorochloromethyl-substituted derivatives may be formed upon condensation of bromodifluoroacetate (Equations (94) and (95)) <1999JFC(95)127> or difluorochloroacetic anhydride (Equation (96)) <2001SL821> with an appropriate nucleophile. NH2

O +

OH

BrCF2

OEt

N

H N

EtOAc Et3N

CF2Br i. PPA, 150 °C

OH

Ph

O

NH2

ð94Þ

O

73% Ph

Heat

+ BrCF2

N CF2Br

ii. NH3 (aq.)

O OH

35%

OEt

N O

N

ð95Þ

CF2Br NMe2

NMe2 N

N (ClCF2CO)2O Pyridine 75%

ð96Þ O

CF2Cl

Difluorochloromethyl groups may be introduced into organic systems by the use of a silicon reagent that is analogous to Ruppert’s reagent (Equations (97) and (98)). The difluorochloromethylating reagent is synthesized by reaction of trimethylsilyl chloride with difluorobromochloromethane in the presence of aluminum <1997JA1572>: O Ph

H

+ Me3SiCF2Cl

OH

THF, NMP TBAF

Ph

CF2Cl

ð97Þ

68% O Ph

6.01.6

H

+ Me3SiCF2Cl

THF, NMP TBAF 85%

OH Ph

CF2Cl

ð98Þ

MIXED HALOFORMS, CHXY2 AND CHXYZ

Recent interest in simple haloforms has concentrated upon the synthesis and spectroscopic measurement of enantiomerically pure samples of simple chiral systems such as CHClFI and CHFClBr. Decarboxylation of appropriate polyhalogenated acetic acids proceeds with retention of configuration allowing the isolation of pure enantiomers <2000MI429, 2003MI541>.

Trihalides

19

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Qing, S. Peng, C. M. Hu, J. Fluorine Chem. 1998, 88, 79.

20 1998JFC(91)179 1998JFC(92)181 1998JOC2656 1998JOC9486 1998TA213 1998TL2973 1998TL3961 1999EJO2471 1999GC9 1999JFC(95)127 1999JFC(96)159 1999JFC(98)75 1999JOC344 1999JOC2873 1999OL2165 1999T275 1999T6329 1999TL5475 1999TL8231 2000JFC(101)199 2000JOC8848 2000MI429 2000MI234 2000MI1037 2000MI331 2000OL2101 2000OL3173 2000T3635 2000T7613 2000TL3069 2000TL5347 2000TL6071 2000TL8777 2001AG(E)589 2001CI(M)83 2001EJO1467 2001JFC(107)45 2001JFC(108)79 2001JFC(110)181 2001JFC(111)161 2001JFC(111)185 2001JFC(112)123 2001MI755 2001OL4271 2001SL77 2001SL821 2001SL1719 2001TL3137 2001TL5929 2002EJO327 2002JFC(114)237 2002JOC9421 2002MI197 2002OL4671 2002SL646 2002SL1697 2002T121 2002TL4317 2003AG(E)3133 2003JFC(121)83 2003JFC(121)239 2003MI541 2003PJC709

Trihalides G. Foulard, T. Brigaud, C. Portella, J. Fluorine Chem. 1998, 91, 179. T. Umemoto, S. Ishihara, J. Fluorine Chem. 1998, 92, 181. J. J. Yang, R. L. Kirchmeier, J. M. Shreeve, J. Org. Chem. 1998, 63, 2656. J. Duan, W. R. Dolbier, Q. Y. Chen, J. Org. Chem. 1998, 63, 9486. S. Lavaire, R. Plantier-Royon, C. Portella, Tetrahedron Assymetry 1998, 9, 213. B. Folleas, I. Marek, J. F. Normant, L. Saint-Jalmes, Tetrahedron Lett. 1998, 39, 2973. L. Tan, C. Y. Chen, R. D. Larsen, T. R. Verhoeven, P. J. Reider, Tetrahedron Lett. 1998, 39, 3961. H. Tamiaki, Y. Nagata, S. Tsudzuki, Eur. J. Org. Chem. 1999, 10, 2471. D. W. Bonniface, J. D. Scott, M. J. Watson, J. R. Fryer, P. London, W. D. S. Scott, G. Webb, J. M. Winfield, Green Chem. 1999, 1, 9. W. R. Dolbier, C. R. Burkholder, M. Medebielle, J. Fluorine Chem. 1999, 95, 127. F. L. Qing, J. Fan, J. Fluorine Chem. 1999, 96, 159. T. Umemoto, S. Ishihara, J. Fluorine Chem. 1999, 98, 75. J. A. Tallarico, L. M. Malnick, M. L. Snapper, J. Org. Chem. 1999, 64, 344. R. P. Singh, G. Cao, R. L. Kirchmeier, J. M. Shreeve, J. Org. Chem. 1999, 64, 2873. S. E. Brantley, T. F. Molinski, Org. Lett. 1999, 1, 2165. B. Folleas, I. Marek, J. F. Normant, L. Saint-Jalmes, Tetrahedron 1999, 56, 275. M. Fedorynski, Tetrahedron 1999, 55, 6329. J. C. Blazejewski, E. Anselmi, M. Wilmshurst, Tetrahedron Lett. 1999, 40, 5475. Y. Kuroki, K. Iseki, Tetrahedron Lett. 1999, 40, 8231. G. K. S. Prakash, E. C. Tongeo, T. Mathew, Y. D. Vankar, G. A. Olah, J. Fluorine Chem. 2000, 101, 199. S. Large, N. Roques, B. R. Langlois, J. Org. Chem. 2000, 65, 8848. J. Crassous, A. Collet, Enantiomer 2000, 5, 429. L. M. Yagupolskii, in Organo-Fluorine Compounds, Houben-Weyl E10a/1, B. Baasner, H. Hagemann, J. C. Tatlow, Eds., Thieme, Stuttgart, 2000, p. 234. K. Iseki, Yuki Gosei Kagaku Kyokaishi 2000, 58, 1037. P. Wolfrum, in Organo-Fluorine Compounds, Houben-Weyl E10b/1, B. Baasner, H. Hagemann, J. C. Tatlow, Eds., Thieme, Stuttgart, 2000, p. 331. T. Billard, S. Bruns, B. R. Langlois, Org. Lett. 2000, 2, 2101. G. K. S. Prakash, M. Mandal, S. Schweizer, N. A. Petasis, G. A. Olah, Org. Lett. 2000, 2, 3173. P. Lin, J. Jiang, Tetrahedron 2000, 56, 3635. R. P. Singh, J. M. Shreeve, Tetrahedron 2000, 56, 7613. T. Billard, N. Roques, B. R. Langlois, Tetrahedron Lett. 2000, 41, 3069. F. Simal, S. Sebille, A. Demonceau, A. F. Noels, R. Nunez, M. Abad, F. Teixidor, C. Vinas, Tetrahedron Lett. 2000, 41, 5347. F. Simal, L. Wlodarczak, A. Demonceau, A. F. Noels, Tetrahedron Lett. 2000, 41, 6071. T. Billard, B. R. Langlois, G. Blond, Tetrahedron Lett. 2000, 41, 8777. G. K. S. Prakash, M. Mandal, G. A. Olah, Angew. Chem. Intl. Ed. Engl. 2001, 40, 589. B. Novari, Chim. Ind. 2001, 83, 83. T. Billard, B. R. Langlois, G. Blond, Eur. J. Org. Chem. 2001, 1467. H. Bozorgzadeh, E. Kemnitz, M. Nikko-Amiry, T. Skapin, J. M. Winfield, J. Fluorine Chem. 2001, 107, 45. X. Zhang, F. L. Qing, Y. Peng, J. Fluorine Chem. 2001, 108, 79. H. Bozorgzadeh, E. Kemnitz, M. Nikko-Amiry, T. Skapin, J. M. Winfield, J. Fluorine Chem. 2001, 110, 181. S. Rozen, D. Rechavi, A. Hagooly, J. Fluorine Chem. 2001, 111, 161. F. L. Qing, X. Zhang, Y. Peng, J. Fluorine Chem. 2001, 111, 185. G. K. S. Prakash, M. Mandal, J. Fluorine Chem. 2001, 112, 123. M. Kawase, Yuki Gosei Kaguku Kyokaishi 2001, 59, 755. N. Takechi, S. Ait-Mohand, M. Medebielle, W. R. Dolbier, Org. Lett. 2001, 3, 4271. G. K. S. Prakash, M. Mandal, G. A. Olah, Synlett. 2001, 77. M. Medebielle, R. Keirouz, E. Okada, T. Ashida, Synlett. 2001, 821. J. M. Barks, B. C. Gilbert, A. F. Parsons, B. Upeandran, Synlett 2001, 1719. J. M. Barks, B. C. Gilbert, A. F. Parsons, B. Upeandran, Tetrahedron Lett. 2001, 42, 3137. F. L. Qing, X. Zhang, Tetrahedron Lett. 2001, 42, 5929. F. Cottet, M. Schlosser, Eur. J. Org. Chem. 2002, 2, 327. R. L. Powell, J. Fluorine Chem. 2002, 114, 237. W. Xu, Q. Y. Chen, J. Org. Chem. 2002, 67, 9421. I. R. Baxendale, S. V. Ley, W. Lumeras, M. Nesi, Comb. Chem. High Throughput Screening 2002, 197. S. Ait-Mohand, N. Takechi, M. Medebielle, W. R. Dolbier, Org. Lett. 2002, 4, 4671. W. B. Motherwell, L. J. Storey, Synlett 2002, 646. J. B. Tommasino, A. Brondex, M. Medebielle, M. Thomalla, B. R. Langlois, T. Billard, Synlett 2002, 1697. V. T. Nguyen, B. Kesteleyn, N. De Kimpe, Tetrahedron 2002, 58, 121. N. Takechi, S. Ait-Mohand, M. Medebielle, W. R. Dolbier, Tetrahedron. Lett. 2002, 43, 4317. J. Joubert, S. Roussel, C. Christophe, T. Billard, B. R. Langlois, Angew. Chem. Intl. Ed. Engl. 2003, 42, 3133. H. Bozorgzadeh, E. Kemnitz, M. Nikko-Amiry, T. Skapin, J. M. Winfield, J. Fluorine Chem. 2003, 121, 83. G. K. S. Prakash, J. Hu, M. M. Alauddin, P. S. Conti, G. A. Olah, J. Fluorine Chem. 2003, 121, 239. J. Crassous, F. Monier, J. P. Dutasta, M. Ziskind, C. Daussy, C. Grain, C. Chardonnet, Chem. Phys. Chem. 2003, 4, 541. M. Fedorynski, A. Blazejczyk, M. Makasa, Pol. J. Chem. 2003, 77, 709.

Trihalides 2003S185 2003SL230 2003SL233 2003T437 2003TL1747

21

B. R. Langlois, T. Billard, Synthesis 2003, 185. L. Jablonski, J. Joubert, T. Billard, B. R. Langlois, Synlett 2003, 230. D. Inschauspe, J. P. Sortais, T. Billard, B. R. Langlois, Synlett 2003, 233. G. Sandford, Tetrahedron 2003, 59, 437. S. Debarge, B. Violeau, N. Bendaoud, M. P. Jouannetaud, J. C. Jaquesy, Tetrahedron Lett. 2003, 44, 1747.

22

Trihalides Biographical sketch

Graham Sandford was born in Manchester. He studied at Durham University, where he obtained a B.Sc. in 1988 and his Ph.D. in 1991 under the direction of Professor R. D. Chambers. After spending 1992 in the laboratories of Professor G. A. Olah at USC, Los Angeles, he returned to Durham as a BNFL Postdoctoral Research Fellow. Subsequently, he was awarded a Royal Society University Research Fellowship in 1996 and took up his present position as Lecturer in Chemistry at Durham in March 2001. His scientific interests include all aspects of organofluorine chemistry, in particular, selective fluorination methodology, heterocyclic, free-radical and carbanion chemistry of fluorinated systems.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 1–22

6.02 Functions Containing Halogens and Any Other Elements J. SUWIN´SKI and K. WALCZAK Silesian University of Technology, Gliwice, Poland 6.02.1 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN 6.02.1.1 Halogen and Oxygen Derivatives (R1CHal2OR2 and R1CHal(OR2)2) 6.02.1.1.1 Tetracoordinated carbon atoms with two identical halogen and one oxygen function attached (R1CHal2OR2) 6.02.1.1.2 Tetracoordinated carbon atom bearing mixed halogens and one oxygen function (R1CHal2OR2) 6.02.1.1.3 Tetracoordinated carbon atom bearing one halogen and two oxygen functions (R1CHal(OR2)2) 6.02.1.2 Halogen and Sulfur Derivatives (R1CHal2SR2 and R1CHal(SR2)2) 6.02.1.2.1 Tetracoordinated carbon atoms with two identical halogen and one sulfur function attached (R1CHal2SR2) 6.02.1.2.2 Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function (R1CHal2SR2) 6.02.1.2.3 Tetracoordinated carbon atoms bearing one halogen and two sulfur functions (R1CHal(SR2)2) 6.02.1.3 Halogen and Se or Te Derivatives (R1CHal2SeR2 or R1CHal2TeR2) 6.02.1.3.1 Tetracoordinated carbon atoms bearing two halogens and one selenium function (R1CHal2SeR2) 6.02.1.3.2 Tetracoordinated carbon atoms bearing two halogens and one tellurium function (R1CHal2TeR2) 6.02.1.4 Halogen and Mixed Chalcogen Derivatives (R1CHal(OR2)(SR3)) 6.02.2 FUNCTIONS CONTAINING HALOGEN AND A GROUP 15 ELEMENT AND POSSIBLY A CHALCOGEN 6.02.2.1 Halogen and Nitrogen Derivatives: General Considerations 6.02.2.1.1 Tetracoordinated carbon atoms bearing two halogens and one nitrogen function 6.02.2.1.2 Tetracoordinated carbon atoms bearing one halogen and two nitrogen functions 6.02.2.1.3 Tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one oxygen function 6.02.2.1.4 Tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one sulfur function 6.02.2.2 Halogen and Phosphorus Derivatives 6.02.2.2.1 Tetracoordinated carbon atoms bearing two halogens and one phosphorus function, and one halogen and two phosphorus functions 6.02.2.2.2 Tetracoordinated carbon atoms bearing one halogen, one oxygen function, and one phosphorus function 6.02.2.3 Halogen and Arsenic Derivatives 6.02.2.3.1 Tetracoordinated carbon atoms bearing two halogens and one arsenic function 6.02.3 FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLY A CHALCOGEN AND/OR GROUP 15 ELEMENT 6.02.3.1 Halogen and Silicon Derivatives 6.02.3.1.1 Dichlorocarbene addition 6.02.3.1.2 Other additions to silanes 6.02.3.1.3 Substitution of silanes by haloalkyl derivatives 6.02.4 Halogen and Boron Derivatives 6.02.5 Halogen and Germanium Derivatives

23

24 24 24 32 33 33 34 49 50 50 50 52 52 53 53 53 59 61 62 62 62 63 63 63 64 64 64 64 64 65 65

24

Functions Containing Halogens and Any Other Elements

6.02.6 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP 15 ELEMENT, A CHALCOGEN OR A METALLOID 6.02.6.1 Halogen and Lithium Derivatives 6.02.6.2 Halogen and Magnesium Derivatives 6.02.6.3 Halogen and Copper Derivatives 6.02.6.4 Halogen and Silver Derivatives 6.02.6.5 Halogen and Zinc Derivatives 6.02.6.6 Halogen and Cadmium Derivatives 6.02.6.7 Halogen and Mercury Derivatives 6.02.6.8 Halogen and Tin Derivatives 6.02.6.9 Halogen and Lead Derivatives 6.02.6.10 Halogen and Ruthenium Derivatives 6.02.6.11 Halogen and Cobalt or Nickel Derivatives 6.02.6.12 Halogen and Palladium or Platinum Derivatives

6.02.1

65 65 65 66 66 66 66 67 67 68 68 68 69

FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN

Apart from broad overviews of haloalkyl systems relevant to this chapter and covering the literature up to 1984 <1985HOU(E5)> and up to 1994 <1995COFGT(6)35> no report of this type has ever been published. A few limited reviews which concentrated mainly on fluorinated oligo- and polymeric materials containing -(CF2O)n- or -(CF2S)n fragments were published. A review seeking to cover recent developments in the field of fluorinated elastomers was published in 2001 <2001MI105>. Heteroatom-containing fluoroelastomers were briefly summarized there (pp. 144–147). The following structures were discussed: -(CF2O)n-, -(CF2S)n-, -(N-OCF2CF2)n-. Also nitrile-containing fluoroelastomers (NC-(CF2)n-O-CF) were presented. A review on polymers (containing OCF2 fragments), which can be applied to a variety of surfaces and manufactured into thin films, has been recently published by Imae <2003MI(8)307>. Caminade et al. published a review on fluorinated dendrimers (some containing OCF2 fragments) and their applications in catalysis, material sciences, and biology <2003MI(8)282>. Application of several different perfluoroalkyl compounds, e.g., perfluoroethers in the biomedical field; in in vivo transport of O2, CO2, and NO was reviewed earlier <1998MI(80)489>.

6.02.1.1 6.02.1.1.1

Halogen and Oxygen Derivatives (R1CHal2OR2 and R1CHal(OR2)2) Tetracoordinated carbon atoms with two identical halogen and one oxygen function attached (R1CHal2OR2)

(i) From ethers Direct halogenation of ethers remains the simplest method for synthesis of perhalogenated compounds of this class. Fluorination of low-molecular weight ethers using elemental fluorine gives products with ratio being a function of the flow rate of fluorine and of carrier gas (usually helium). Direct fluorination of dioxane using elemental fluorine has afforded perfluorinated system in a moderate yield, whereas application of a mixture of sulfur tetrafluoride and hydrogen fluoride has led to the formation of 2,2,3-trifluorodioxane in a high yield. Electrochemical fluorination of ethers leads to perfluorinated products in moderate yields. Electrochemical fluorination of a range of oxanes also results in the formation of the corresponding perfluorinated products in only moderate yields <1995COFGT(6)35>. Combination of sodium fluoride and elemental fluorine has successfully been applied to fluorination of ethers in perhalogenated alkanes as the solvents. The appropriate perfluorinated ethers were obtained in high yields (Scheme 1) <1995JA4276, 1996SC375>. Fluorination of 5,7,9,11-tetraoxapentadecane using the same system has produced a mixture of perfluorinated ethers resulting from chain cleavage <1995JA4276, 1996SC375>. Fluorination of an alkoxyalkyl ester of perfluorinated acid using elemental fluorine at elevated pressure affords perfluorinated product in a moderate yield. It is worth mentioning that the ester function is preserved (Equation (1)) <2001JFC(112)109>.

25

Functions Containing Halogens and Any Other Elements F2, NaF, ClF2CCCl2F

O

75%

O

O

O

CF3

F F F2, NaF, ClF2CCCl2F

O

F F F F F F F F F F F3C

O 3

32%

F F

F F F F FF F3C

O

FF F F

O3

F F

CF3 F F

Scheme 1

O

O

F F F CF3

F2, C6H6, 20–40 °C, <1500 torr

R

F

75%

O

F

O

O

F F

R O

ð1Þ

R = –CF(CF3)OCF2CF2CF3

Electrochemical fluorination of N-(2-hydroxyethyl)morpholine leads to the corresponding acyl fluoride (Equation (2)) accompanied by a mixture of perfluorinated products resulting from the chain or ring cleavage and subsequent fluorination of the produced fragments <1999JFC(97)229>. Tetrahydrofuran, when treated with boron trichloride in the presence of bis(trifluoromethyl)cadmium-acetonitrile complex, undergoes ring-opening reaction followed by halogenation to produce 4-chlorobutyl difluoromethyl ether <1995JFC(73)229>. O

O

F N

HF, 7–8 °C, ~10 h

N

25% OH

F

ð2Þ F

O

F

Photochlorination of partially fluorinated ethers was also investigated; the appropriate chloroethers have been obtained in moderate yields <1995JOC1319>. Chlorination of p-methoxybenzoyl chloride using chlorine in the presence of phosphorus pentachloride affords p-(trichloromethoxy)benzoyl chloride in an excellent yield (Equation (3)) <2000JFC(103)81>. O MeO Cl

PCl5, Cl2, 200 °C 92%

O

ð3Þ

Cl3CO Cl

(ii) From mixed trihalomethanes No further advances have occurred in this area since the publication of <1995COFGT(6)35>.

(iii) From dihaloethers Selective further fluorinations of haloethers using manganese trifluoride or sodium fluoride have been reported (Scheme 2) <1996JFC(80)86, 1997JFC(85)111>. Treatment of haloethers, containing a mixed halogen function, with sevoflurane (1,1,1,3,3,3hexafluoro-2-(fluoromethoxy)propane) in the presence of antimony pentachloride <1998JFC(88)51, 2001JFC(111)11> or bromine trifluoride <2000JFC(102)363> results in halogen substitution. In the latter reaction respective fluorinated ethers have been obtained in moderate to good yields (Scheme 3). Substitution of a chlorine atom in trichloromethyl group using sevoflurane and antimony pentachloride was reported later <1999JFC(94)1>. A fluorine atom through a reaction with hydrogen fluoride in the presence of cobalt difluoride and porous aluminum trifluoride can substitute an -chlorine atom in mixed haloalkoxyalkanes (Scheme 3) <2001JFC(112)145>.

26

Functions Containing Halogens and Any Other Elements F

O

MnF3, 75 °C, 6 h

CF3

85%

F

O

F F3C

O

65%

F F Cl

F F

NaF, 85–95 °C, 6 h

CClF2

CF3

O

F3C

F F

MnF3, 50 °C, 5 h

O

Cl

O

45%

F

F

F F CH2F

F

Scheme 2

Cl F

Cl3C

CF3

O

SbCl5, sevoflurane, 5–10 °C, 1 h

Cl Cl

90%

CF3 F Cl F Cl

C F3 CF3

F

66%

CF3

O

F

SbCl5, sevoflurane

CF3

O

F

C F3 CF3

F F

CoF2, HF, AlF3, 200 °C, 1 h

O

O

F Cl

85%

F

O F

Scheme 3

Polyfluorinated ethers Rf CH2ORf react with fluoroethylenes in the presence of SbF5 catalyst under mild conditions. The reaction of CF3CH2OCF2CF2H with F2C¼CF2 results in the formation of CF3CH2OCF(C2F5)CF2H in a high yield. In contrast to that, the condensation of CF3CH2OCF2CF2H with F2C¼CFH affords CF3CH2OC(CHFCF3)CF2H as a major product (Scheme 4). A mechanism for the reactions was discussed <2001JFC(112)117>.

F F3C

F F H

O

F3C

F H

O

F3CHFC

F2C=CHF, 25 °C, 5 h

F

O

F3C

76%

F F

F

F2C=CF2, SbF5, 25 °C, 12 h

F3C

61%

F

O

CF2CF3 F H F CHFCF3 F H F

Scheme 4

A chlorine atom in polyfluorinated ether was exchanged by a fluorine one using trifluoroboride (Equation (4)) <1993JPS791>. F2HC

O

CF3 H Cl

BF3

F2HC

O

CF3 H

ð4Þ

F

Transformations of polyfluoroalkyl ethers have also been described <2002JFC(114)51>. Lubricating oils and greases for magnetic recording devices, containing partially esterified phosphates and phosphonates or salts of phosphate and phosphonate esters were prepared by reaction of mixed perfluoroalcohols or perfluorodiols with a phosphorus acid precursor i.e., phosphorus oxychloride in the presence of an amine acid scavenger <2003USP073588>.

27

Functions Containing Halogens and Any Other Elements (iv) From carbonyl derivatives

Several methods for conversion of carbonyl compounds into ethers perhalogenated in alkyl (cycloalkyl) groups have been described. Among others electrochemical fluorination of acyl chlorides and esters has been used. The sulfur tetrafluoride has been applied for conversion of a variety of anhydrides, esters, and formate esters into compounds with difluoromethyl groups. Aromatic o-diacids treated with sulfur tetrafluoride can form cyclic ethers in addition to perfluorination of other substituents <1995COFGT(6)35>. Phosphorous pentachloride, which reacts with a variety of formate esters to yield the corresponding ,-dichloro diethers <1995COFGT(6)35>, has recently been used successfully for the conversion (Scheme 5) of methyl formate <1996ZOR1186> and diphenyl carbonate <1996AJC1261>.

O H

PCl5 Me

OMe

O

Cl Cl

O PhO

Cl

PCl5, 180 °C, 24 h OPh

Cl

PhO

97%

OPh

Scheme 5

Acyl fluorides can be transformed in moderate yields into perfluoroalkyl methyl ethers using triethylamine–hydrogen fluoride complex (Equation (5)) <2002JFC(118)123>. Oxalyl difluoride treated with ethyl ester of trifluoromethanesulfonic acid has afforded ethoxy-difluoroacetyl fluoride in a moderate yield (Scheme 6) <2002JFC(113)97>. Oxalyl difluoride has also been used in reaction leading to the ring-opening in perfluorinated (methyl)oxiranes (Scheme 6) <1995JFC(75)163>. Perfluorinated (methyl)oxiranes when treated with several fluorinating agents gave appropriate derivatives of perfluorinated alkoxy acetyl fluorides in moderate-to-good yields (Scheme 7) <1996T9755, 2002JFC(114)51, 1999ZPK(72)425>. The use of ammonium- and phosphonium perfluorocyclobutane ylides, prepared with perfluorocyclobutene and tertiary amines or phosphines as a masked fluorine anion source, has been demonstrated in several reactions <1996T9755>. Et3N.3HF, EtOH

F F F3 C

O

(CH3O)2SO2 68%

F

O F

F

F F O

F F

F F O

O

71%

O

F3C

F

F O

F KF, 0 °C, 16 h 58%

ð5Þ

O

F3C

O S F3 C O O CsF, diglyme, 20 °C, 24 h

O

F

F F

O F

F F F CF3 O

F F F F

O

O F

Scheme 6

The reactions of oxalyl fluoride with electrophiles in the presence of alkali metal fluoride afford ,-difluoroethers. In the reaction with CF3CH2O3SCF3 or CH3CH2O3SCF3, synthesis of di-ether (ROCF2CF2OR) and mono-ether as a by-product (ROCF2COF) was achieved (Scheme 8) <2002JFC(113)97>.

28

Functions Containing Halogens and Any Other Elements F F3C

F F

O

F F3C

F F

O

O

F F

Et3NC4F7. BF4, MeCN, 2 h

O

F3C

82%

F

F F F CF3 F F F CF3

F F

CsF, various solv.

O

F3C

22%

O

O

F F F CF3

F

Scheme 7 F

O

F

O

F F

CF3CF2OTf, CsF, rt, 24 h F3C

Diglyme 56%

O

O

CF3

F F

Tetraglyme 63%

Scheme 8

A new synthetic procedure for the preparation of perfluoro(alkoxyalkanoyl) fluorides, precursors of perfluorinated vinyl ether monomers, from nonfluorinated alkoxyalcohols has been developed. The desired perfluoro(alkoxyalkanoyl) fluoride can be obtained from its hydrocarbon counterpart alcohol and an available perfluoroacyl fluoride as is shown (Scheme 9) <2001JFC(112)109>. Transformation of benzaldehydes to difluoromethoxybenzenes using xenon difluoride is enhanced by silicon tetrafluoride <1999JFC(98)163>. It was also found that a relatively new reagent namely bromine trifluoride converts aliphatic nitriles into trifluoromethyl group when a neighboring carboxylic moiety is present. In the case of ketonitrile, a participation of the internal nucleophilic oxygen in attacking the nitrile carbon was also observed <2001JFC(111)161–165>. F F3C

OC3F7 F O F

CF3 C3F7 O

F O

O R HO

O

F

99%

O

O

NaF (30 mol.%), 140 °C

O

RHOH C3F7

F CF3

F CF3

1,1,2-Trichlorotrifluoroethane 25–40 °C, 21–86%

O

C3F7 F CF3

O

20% F2/N2, 0.2 MPa C3F7

RHO

RFO

O

C3F7

F CF3

Scheme 9

(v) From alkoxyhaloalkenes Addition of fluorine to the double bond in alkoxyfluoroalkenes has not been reported in reviews yet. It can be achieved using some fluorinating agents like hydrogen fluoride, boron trifluoride, or cobalt trifluoride to afford products, in which former alkene substituents are perfluorated while alkoxy groups do not contain additional fluorine atoms. Yields of the products depend both on the fluorinating agent and reaction conditions (Scheme 10) <1996JOC9605, 2000MI(3)343>. Preparation of alkoxydi(tri or tetra)chloroalkanes by addition of dry hydrogen chloride or dry chlorine to alkoxychloroalkenes has already been discussed <1995COFGT(6)35>. More recent reports on chlorination or bromination of alkoxyhaloalkenes have not been located.

(vi) From haloalkenes The addition of primary alcohols to halogenated alkenes proceeds rapidly in the presence of metal alkoxides, giving the corresponding alkoxyhaloalkanes in high yields <1995JFC(74)273, 1997AG136, 2000JFC(102)363>. Also a variety of primary and tertiary alkyl hypohalides are added at low temperatures affording respective addition products in high yields <1995JFC(74)199>.

29

Functions Containing Halogens and Any Other Elements F

OCF3

F

F

F

O

F

F

F3C

F F

F

F F

CoF3, –196 to –20 °C, 0.5 h

F3C

45%

O F F

CoF3, –196 to –20 °C, 0.5 h

O

F3C

55%

F

F I

O

F3C

84%

O

F

F F

ICl, HF, BF3, 70 °C, 20 h

F F

Scheme 10

Perfluorinated vinyl ethers react smoothly with alcohols in the presence of deprotonating agents to give appropriate ethers in moderate yields (Scheme 11) <2000JFC(106)13, 2002JFC(117)149>. Addition of trifluoroethanol to the perfluorinated methyl vinyl ether has been accomplished using aqueous potassium hydroxide at an elevated temperature (Equation (6)) <1999JFC(95)5>. Also other compounds containing sufficiently acidic proton can be added to perfluoroalkenes in aprotic solvents in the presence of metal hydroxides (Scheme 12) <1998JCR(S)(4)192, 1998JMC1092, 2000JFC(101)91, 2000JFC(103)129, 2002JFC(117)149>. Addition of alcohols to perfluorinated alkoxyalkenes is also possible under photochemical conditions <1996JFC(80)135>. F F F3C

F

F F

F

O

O

F F F CF3

F

F3C

O

O

F

F3C

O O F F

F F F CF3 F

n-C6H13OH, BuLi, THF, 20 °C

F

F O

F3C

38%

F F F CF3 F

F

F F O

54%

F

F F

F F

MeOH, MeONa, 20 °C

O

F OC6H13

F F F CF3F

Scheme 11

F

F3C OH KOH, H2O, 100 °C, 20 h

F

F

OCF3

N OH

F

CF3 F DMF, NaOH,

O

F F CF3

N O

80%

F O

Me OH Me

ð6Þ

CF3

F

O

HO

O

O

92%

F O

F F F3C

F

F

F

CF3

KOH, DMSO, 60 °C, 5 h 92%

Scheme 12

F

F

F

Me

O CF3

F

F

F

O Me

CF3

30

Functions Containing Halogens and Any Other Elements

Epoxidation of chloroalkenes is a convenient route to ,-dichlorooxiranes—useful intermediates in the enantioselective synthesis of azido- and aminoacids. Perfluoroalkenes react with sulfur trioxide to give cyclic perfluoro-2--sulfones in excellent yields. Perfluoroalkenes also react with halogen monofluorosulfates to yield both 2-haloalkylfluoroalkyl fluorosulfates and vicinal bis(halosulfonyloxy)fluoroalkanes <1995COFGT(6)35>. A series of nucleophiles was treated with [1,1,2,4,4,5,7,7,8,8,9,9,9-tridecafluoromethyl3,6-dioxanon-1-ene] as a representative of perfluoro(alkyl vinyl ethers). All the reactions were completely regioselective with the nucleophilic attack on the terminal carbon atom. Reactions of hydroxy compounds, thiols, and sec-amines afford the desired products, while butyllithium, tributylphosphane, or complex hydrides cause displacement of vinylic fluorine (Scheme 13) <2002JFC(117)149>. CF3

CF3

NuH, BuLi, THF

F2C=CFOCF2CFO-CF2CF2CF3

–75 °C to rt, 5 days

NuF2CCHFOCF2CFO-CF2CF2CF3 NuH

Yield (%)

n-C6H13OH n-C16H31OH p-F3CSC6H4OH PhSH Et2NH (CH2)5NH

38 (unstable) 41 30 55 52 (unstable) 79 (unstable)

Scheme 13

(vii) From thiocarbonyl derivatives A novel, versatile route to difluoroalkoxyalkanes has been offered using bis(dimethoxyethylene)amino sulfur trifluoride in the presence of antimony trichloride. A number of thiocarbonyl methyl esters have been converted to the corresponding difluoroalkoxyalkanes in high yields (Equation (7)) <1999JOC7048, 2000JOC4830>. S R

O

Me

DAST, SbCl3, CH2Cl2, 20 °C, 4 h

F

F

R

O

Me

ð7Þ

R = Ph, 96%; cyclohexyl, 95%

S-Methyl thioxanthates, reacting with hydrogen fluoride or bromotrifluoride in the presence of DBH (1,3-dibromo-5,5-dimethyl)hydantoin), produce appropriate difluoroalkoxyalkanes. The latter reaction can be described as an oxidative desulfurization–oxidation process (Equation (8)) <1999JFC(97)75, 2000BCJ(73)471>. Sulfuryl chloride has been used for transformation of acetyl methoxy(thiocarbonyl)sulfide to the corresponding disulfenyl chloride <1997JMC864>. S RO

70% HF/pyridine, DBH, CH2Cl2, –78 to 0 °C, 1 h S

Me

F F R

R

= Decyln,

S

Me

ð8Þ

89%; p -BrC6H4, 62%

(viii) From mixed haloalkanes A halogen atom (Cl, Br, or I) at or position to a carbon atom bearing fluorine is easily substituted by the phenolate anion. In the presence of sodium hydroxide the reaction occurs easily in both protic and aprotic solvents. Substitution predominates over elimination and appropriate products are formed in moderate to good yields (Scheme 14) <1997KGS(33)967, 1998T4849, 1999KFZ(33)40, 2000JFC(102)369, 2000JFC(105)129, 2001JFC(107)89, 2001JMC2869, 2002T4077, 2002TL7353>. Sometimes pressure is necessary to accomplish the reaction, however, it does not help to prevent the elimination <2001JFC(107)89>.

31

Functions Containing Halogens and Any Other Elements F I

F

F

F

Cl F F

O

p-cresol, KOH, DMSO, 80 °C, 6 h

F

O

26%

F

F

F

Me O p -cresol, NaH, 1,4-dioxane, ∆, 3 h

O

100%

OH

OH

F O

F

Me

HO I F F

F

OEt KF, DMSO, 120–130 °C, 6 h

F

O

50%

F

F

F

O

F

OEt Phenol, KOH, H2O, 250 °C, 11 h

O

36–480 torr F 3C

Cl 72%

F I

OEt

i

I

F

F

OEt

F F

O

F

O

O

O

i. phenol, NaH, DMF, 20 °C, 4 h, 80%

Scheme 14

(ix) From trihaloalkyl derivatives Treatment of 2,2,2-trifluoroethyl chloride with alcohols or phenols and aqueous potassium hydroxide in an autoclave at 240–280 C gives the corresponding 2-chloro-1,1-difluoroethyl ethers in good yields (Scheme 15) <2002JFC(113)79>.

F

ROH, KOH, H2O F3 C

Cl

60–100 atm. 10–15 h, 250–285 °C

RO

F

ArOH, KOH, H2O F 3C

F

Cl

Cl

40–50 atm. 250 °C, 11 h

F Cl

ArO

R

(%)

Me Et Bun But MeCF2

55 67 42 0 70

Ar

(%)

Ph p-MeC6H4 o-MeC6H4 p-(But)C6H4

76 73 52 67

Scheme 15

(x) From other compounds Alcohols can be transformed into alkyl perfluoroethyl ethers using 2-trifluoromethyl-1,2-dithianylium triflate (Scheme 16) <2003TL5995>.

32

Functions Containing Halogens and Any Other Elements S +

i. NaH, ii .

CF3

– F3CSO3

S

RO

CF3

S

S

ROH

F

DBH, HF–Py RO

F F

F

83%; p-O2NC6H4O- 23%

54%;

R = c-C6H11–

F

Scheme 16

Fluorination of esters by gaseous fluorine leads to perfluorination of both alkyl groups without affecting the ester function (Equation (9)) <1998JA7117>. The same concerns fluorination of alkoxyesters (Scheme 17) <2001JFC(112)109>. O C11H23

O

F2, 25 °C

C11F23

F

O Cl

O

Cl

F C F 3 7 O CF3

ð9Þ

C4F9-t

C4H9-t

O

F

O

O

O

F

F F

i

F

F

F

F

O Cl

63%

F

F

Cl

CF3

F F

O

C3F7 O

CF3

i. F2, 20–40 °C, 0–1500 torr O C10H21

O

O

F2, 20–40 °C, 0–1500 torr

O

O C3F7 CF3

F2, 20–40 °C, 0–1500 torr

F

O

F

78%

O F 3C

CF3

F OC3F7 CF3

O

F F

F F

O

F

69%

F O

O

C10F21

O

O

F O

F F OC3F7 CF3

O C3F7 CF3

O CF3

Scheme 17

6.02.1.1.2

Tetracoordinated carbon atom bearing mixed halogens and one oxygen function (R1CHal2OR2)

Addition of chlorine to methyl perfluorovinyl ethers has been reported as a versatile route to chlorofluoroethers (Equation (10)) <1996JOC8024, 2001T4111, 1998JFC(88)51>. A highly selective exchange of chlorine by fluorine atom in trichloromethyl group of hexafluoroisopropyl trichloromethyl ether, using dichloroacetyl fluoride, has been observed. The use of antimony pentachloride in a similar process has also been reported <1999JFC(94)1>. Introducing four chlorine atoms into tetrafluoroethyl methyl ether has been achieved by photochemical chlorination using gaseous chlorine (Equation (11)) <1995JOC1319, 1999JFC(93)93>. F

OMe

F

F

Cl2, –196 to 20 °C, 5 min 97%

Cl F Cl

F OMe

F

ð10Þ

33

Functions Containing Halogens and Any Other Elements F

F Cl

Cl2, hν, 30 h

F3C

Me

O

F3C

74%

O

ð11Þ

CCl3

A synthesis of chiral enantiomerically pure chlorofluoromethyl tetrafluoroethyl ethers was described. The starting racemic trichloromethyl ether was subjected to fluorination with antimony trifluoride– bromine giving dichlorofluoromethyl ether in 51% yield. Irradiation of the latter with UV light in 2-propanol afforded racemic ether in 49% yield. Application of the above conditions to enantiomerically pure (R) and (S) ethers gave the target ethers respectively with only a very little erosion of the enantiomeric excess (ee). The importance of the latter result comes from the following: volatile halogenated chiral ethers are often used as anesthetics; in common with many other chiral pharmaceuticals, the optical antipodes can differ in pharmacological profile (Scheme 18) <1995JOC1319>. O Cl3C F

CF3

SbF3, Br2

H

45–56%

F Cl

O Cl

F

CF3

2-Propanol, hν 43–47%

H

F H

O Cl

F

CF3 H

Scheme 18

6.02.1.1.3

Tetracoordinated carbon atom bearing one halogen and two oxygen functions (R1CHal(OR2)2)

Compounds with a tetracoordinated carbon atom bearing one halogen and two oxygen atoms seem to be quite common and well known. Numerous examples of compounds of this class exist and their syntheses have been reviewed <1995COFGT(6)35>. The compounds are usually prepared either from 1,3-dioxolanes or from o-formates using a variety of halogenating agents. More recently one unusual example of the synthesis has been reported. Fluorosulfonic acid and sulfur dichloride reacting with trifluoromethyl trifluorovinyl ether yielded a product containing rests of both reagents added to the starting alkene. The products contain a tetracoordinated carbon atom bearing one halogen and two oxygen atoms (Scheme 19) <1996IZV(7)1745>. It appears that no further advances have occurred in this area since the publication of <1995COFGT(6)35>. SCl2, HSO3F, 30–35 °C

F

F

F

O CF3

F

F

O S O OF

33%

F Cl S O CF3

Scheme 19

6.02.1.2

Halogen and Sulfur Derivatives (R1CHal2SR2 and R1CHal(SR2)2)

The synthetic methods for preparing carbohydrates bearing a C-branched substituent of the type CF2-Y (e.g., n-CnF2n+1) where Y = heteroatom (O, S, P) were reviewed by Plantier and Portella. Examples of the syntheses are given in Scheme 20 <2000CAR119>. F

O

PhSH, AIBN F

(OR)3

PhH, ∆, 92%

F

O (OR)3

F

F

O F (OR)4

SPh

F

PhSH, AIBN

F

PhH, ∆, 79% (OR)4

Scheme 20

SPh

O

34 6.02.1.2.1

Functions Containing Halogens and Any Other Elements Tetracoordinated carbon atoms with two identical halogen and one sulfur function attached (R1CHal2SR2)

(i) From sulfides Halogenation of sulfides is the most popular method for the preparation of compounds described in this sub-chapter. Several new examples of fluorination of sulfides, containing other functional groups (not reported in <1995COFGT(6)35>) concern reactions under electrochemical conditions. The first reports on electrochemical difluorination of sulfides published by Fuchigami and co-workers appeared in 1995 (Scheme 21) <1995JOC3459, 1995JFC(73)121>.

i. Et3N–3HF, MeCN ii. aq. NH 4OH

F Ph

O

S

Et

F F Ph

O

S

Electrolysis, 57%

O

Et

O

Scheme 21

Carbonyl group or triple CC bond can serve in those fluorinations as activating groups (Scheme 22) <2001TL3009, 2002T5877>.

F F Ph

O

S

Ph

Et3N–3HF, MeCN

O

O

S O

Electrolysis, 11%

Et3N–5HF, MeO Ph

Ph

OMe

S

S

Electrolysis, 77% F

F

Scheme 22

Triethylamine–hydrogen fluoride complex was also used under electrochemical conditions for fluorination of sulfides in the -position to sulfur atom in compounds containing carboxyamide group (Equation (12)) <1999JFC(93)53>. O

O

Et3N–3HF, MeCN

Ph S NH2

Ph S

Electrolysis, 27% (not isolated)

ð12Þ

NH2

F

F

,-Difluorination of unactivated methylene group in sulfide was reported too (Scheme 23) <2001TL4861>.

Ph

S

O

O O

Et3N–3HF, MeO

OMe

Electrolysis, 40 °C, 68%

Scheme 23

F F Ph

S

O

O O

35

Functions Containing Halogens and Any Other Elements

Sulfides already containing one -fluoro atom can be fluorinated further to difluoro derivatives (Equation (13)) <1995T2605>.

F Ph S

F

Et3N–3HF MeCN, 2 h electrolysis

Ph F

Ph S

ð13Þ

Ph

F F

Fluorine atoms exchange with hydrogen in methylene group of sulfides, activated by carbonyl or cyano group linked to sulfur, in reactions with tetraethylammonium fluoride–hydrogen fluoride complex (Scheme 24) <1997JOC8579>.

n-C7H15 S

Et4NF–4HF

CO2Et

n-C7H15 S

MeCN, 50% electrolysis

Ph S

N

F

Et4NF–4HF

Ph S

MeCN, 50% electrolysis

CO2Et F

N

F F

Scheme 24

Electrochemical conditions have also been applied to difluorination of quinolin-2-yl propan2-on-1-yl sulfide (Equation (14)) <1999JOC138>.

Et4NF–3HF, MeO

O N

Electrolysis, 5% (not isolated)

S

O

OMe N

ð14Þ

S F

F

When the reaction of fluorination of sulfides is carried out in the presence of 1,3-dibromo5,5-dimethylhydantoin, fluorine atoms can substitute both hydrogen atom and carboxylic group attached to a methylene carbon atom (Scheme 25) <1998JFC(87)215>.

Ph S

CO2H C6H4-Cl-p

F

i 30%

Ph S

F

C6H4-Cl-p

i. Et3N–3HF, CH2Cl2, 1,3-dibromo-5,5-dimethylhydantoin, electrolysis

Scheme 25

Addition of pentafluoroiodine to triethylamine–hydrogen fluoride complex enables one to perform difluorination in hydrocarbon solvents without electrolysis. Usually improved (moderate or high) yields of products are obtained, though the reactions carried out at lower temperatures require a considerable length of time (Scheme 26) <2001CL222, 2002BCJ(75)1597>.

36

Functions Containing Halogens and Any Other Elements Ph

F F

Ph

S

IF5–Et3N–3HF, hexane, 63 °C, 4 h

O

Ph

S

45%

F Et

Ph

F

O F F F

IF5–Et3N–3HF, heptane, 74 °C, 1 h

Et

82%

S

S O

O Ph

O

S

S

C4H9

O

C4H9

F F

IF5–Et3N–3HF, hexane, 40 °C, 216 h

Et

Ph

F

F F Ph

36% F

O

S

Et

O F F F

IF5–Et3N–3HF, hexane, 40 °C, 4 h Et

80%

S

Et

O

IF5–Et3N–3HF, hexane, 40 °C, 216 h Et

O

S

O

Et

N

S

69%

O

F S

F F p-ClC6H4

36%

O

Ph

S O

IF5–Et3N–3HF, heptane, 80 °C,12 h

O

Ph

Ph

79%

N

S

Et

F F

IF5–Et 3N–3HF, heptane, 40 °C, 6 h

O Ph

O

S O

O

p-ClC6H4

Ph

59%

Ph

S

F F

IF5–Et3N–3HF, hexane, 63 °C, 4 h Et

O

Ph

F

F

S

O

O

Scheme 26

Rather recently a new fluorinating agent namely N-fluoro-2,4,6-trimethylpyridinium triflate has been shown to efficiently difluorinate several sulfides in the presence of zinc dibromide. The reaction occurs in chlorinated hydrocarbons at elevated temperatures affording products in high yields (Scheme 27) <2000CPB1097>. In another paper the same authors have reported even higher yields of the products (Scheme 28) <2001CPB173>.

O p-MeOC6H4

S

i 64%

O p-MeOC6H4

S F F

i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 100 °C, 1.5 h Ph

Ph

S O

i 76%

F F Ph

S

Ph

O i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 105 °C, 1.5 h

Scheme 27

37

Functions Containing Halogens and Any Other Elements F Et

F

F F F

i Et

85%

S

F

S

O

O

i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl Ph

Ph

S O

F F

i

Ph

82%

Ph

S O

i. ZnBr2, N-fluoro-2,4,6-trimethylpyridinium triflate, Cl2HCCH2Cl, 85–105 °C

Scheme 28

A high yield of difluorinated sulfide can be obtained by the treatment of ethyl -(phenylthio)acetate with difluoroiodotoluene in dichloromethane at a low temperature (Scheme 29) <2000TL4463>.

Ph

O

S

F F

Difluoroiodotoluene, CH2Cl2, 0 °C

Et

Ph

O

S

80%

O

Et

O

Scheme 29

Triethylamine–hydrogen fluoride in acetonitrile, in the presence of zinc dibromide, was used for difluorination of only one methylene group in 2,8-dioxa-5-thia-nonan-3,6-dione (Equation (15)) <2002SL996>. F F O

O

S O

Et3N–3HF, ZnBr2, MeCN

O

O

O

S O

ð15Þ

O

Moderate yields of -bromo-,-difluoro--methylthioketones are obtained from ,-dimethylthio-,-unsaturated ketones by treating them with hydrogen fluoride–pyridine in the presence of 1,3-dibromo-5,5-dimethylhydantoin (Scheme 30) <1998TL9651> or mercury trifluoroacetate (Equation (16)) <2000JFC(101)35> as catalysts.

O

S

O Pr

S

HF, pyridine, i, CH2Cl2, –78 °C, 2 h 39%

Et

S Et Br O

S

O

S

F F

Pr

HF, pyridine, i, CH2Cl2, –78 °C, 2 h

F F S Br

39% i = 1,3-dibromo-5,5-dimethylhydantoin

Scheme 30

O Ph

S

Pyridine–6HF, Hg(OCOCF3)2, CH2Cl2, 20 °C, 24 h S

76%

O

F F

Ph

S Et

ð16Þ

38

Functions Containing Halogens and Any Other Elements

Dichlorination of sulfides is a popular route to ,-dichloroalkyl sulfides and can be achieved easily using several chlorinating agents, e.g., sulfuryl dichloride. Pommelet and co-workers published several examples of such chlorination (Scheme 31) <1997T12565, 2002SL996, 1996TL2413>.

O

O Ph

SO2Cl2, CH2Cl2

S

Ph

S

72.5% O

S

Et

SO2Cl2, CH2Cl2 88.5%

O

Cl

Cl Cl

Cl O

Et

S O

O

O

S O

Ph

O

O

81.5% SO2Cl2, CH2Cl2, 20 °C, 2 h

O

S

Cl SO2Cl2, CH2Cl2

96.5%

O O

SO2Cl2, CH2Cl2

S

81%

Cl O

S O

O Cl

Cl Ph

O

S O

O S Cl Cl

Scheme 31

Partly fluorinated sulfides are dichlorinated in high yields using sulfuryl dichloride in chlorinated hydrocarbons (Scheme 32) <1997BSF697>. Under the conditions sulfuryl dichloride leaves the triple CC bond untouched (Equation (17)) <1997SC2993>.

F Ph

S

F F

F Ph

SO2Cl2, Cl2HCCH2Cl, ambient temp. 2 h

S Cl Cl

85%

F F

Cl Cl n-C3F7 S Pr

SO2Cl2, CH2Cl2, 2 h

n-C3F7

S Pr

S

88%

F

90%

F

Cl

Cl

SO2Cl2, CH2Cl2, 2 h

Et

F F

S

F

Et

F

Scheme 32

Ph S C6H13-n

SO2Cl2, CCl4, 0 °C, 30 min

Ph S Cl

C6H13-n

ð17Þ

Cl

Japanese chemists have reported an interesting dichlorination of enantiomerically pure chiral sulfide, not observing racemization at a carbon atom adjacent to the chlorinated one (Scheme 33) <2000TL4603>.

39

Functions Containing Halogens and Any Other Elements O

O O

O

SO2Cl2, CH2Cl2, 20 °C, 3 h

Ph S

F

Ph S

100%

F

Cl Cl F F

F F

Scheme 33

Gaseous chlorine was applied for ,-dichlorination of sulfide in methylene group activated by electron-withdrawing methanesulfonyl moiety <1997AJC683>. Gaseous chlorine is also easily added to ,-unsaturated sulfides. The addition can be followed by the replacement of a hydrogen atom (Scheme 34) <1998ZOR1792>, alkylthio- or alkyl-groups by additional chlorine atoms (Scheme 35) <2002IZV(6)948>.

Cl2, CCl4, 10 °C, 2.5 h

S

Cl

S Cl

68%

Cl Cl

Cl

Scheme 34

Bn S

Bn

Cl Cl S

Cl2, –78 to –50 °C, 29 h

S CO2–

Cl

CO–2 F3C Cl

49%

F3C

Scheme 35

Phosphorus pentachloride was used for unsymmetrical dichlorination of bis(benzoylmethyl)sulfide (Equation (18)) <1995ZOR1257>. Ph

Ph

S O

Cl

PCl5, CH2Cl2

Ph

43%

O

Cl Ph

S O

ð18Þ

O

Trifluoromethylation of organic halides with FO2SCF2CF2OCF2CO2K in DMF at 45 C was reported <1996JFC(78)177>. -Chlorinated--fluorinated sulfides are synthesized in good yields by nucleophilic fluorination of the corresponding dichlorosulfides. It can be achieved, e.g., with Et3N–3HF in refluxing acetonitrile <1996TL2413, 1997T12565>. Also chlorination of -fluorinated sulfides using SO2Cl2 leads to the formation of chloro--fluorosulfides, sometimes in very high yields (Schemes 36 and 37) (Table 1).

R S

CO2Me

2SO2Cl2

R

Cl S

Cl

PH2F3, CCl4

F S

CO2Me

2SO2Cl2 CO2Me

ca. 100%

R = Ph, Me, CO2Me

Scheme 36

R

Cl S

R = Ph 42%, Me 37%, CO2Me 75% R

R

Cl S

F CO2Me

F CO2Me

40

Functions Containing Halogens and Any Other Elements R R'

S

A

2SO2Cl2

R R'

Cl S

Cl

Et3N–3HF

A

R R'

Cl

F

S

A

Scheme 37

Table 1

Substituents and yields of products depicted in Scheme 37

R 25 C, 15–24 h Ph Me MeCO2 Ph Me Me Ph 180 C, 24–36 h Ph Me Ph Me Me Ph Me

R0

A

Yield (%)

H H H H H Me H

CO2Me CO2Me CO2Me COMe COPh COPh CN

67 78 56 41 67 54 0

H H H H Me H Me

CO2Me CO2Me COMe COPh COPh CN CO2Me

77 70 65 70 57 50 57

(ii) From halofluoroalkanes and derivatives The extensive studies on photochemical reaction of fluoroiodoalkanes with both methyl sulfide and dimethyl disulfide were reviewed earlier in <1995COFGT(6)35>. Photochemical substitution reaction of fluoroiodoalkane by thiole anion has recently been performed, leading to the corresponding sulfide in a high yield (Scheme 38) <1998SL1243, 2001JFC(108)95>.

n-C8F17I

RSH, liq. NH3, UV

n-C8F17 S

83% n-C6F13I

RSH, liq. NH3, UV 79%

RSH = HS

OEt O

n-C6F13 S

OEt O

OEt O

Scheme 38

Several recent reports bring examples of the nucleophilic substitution of 1-iodoperfluoroalkanes by thiols carried out in the absence of irradiation (Scheme 39) <1995JFC(74)123, 1998MI(8)1193, 1997JOC1457, 1995JOC6186>. Reactions of derivatives of ethyl difluoroiodoacetate with thiole anions either pre-generated or formed in situ are also known (Scheme 40) <2002TL2949>. Terminally iodinated perfluorohexane reacts with a derivative of 2-naphthothiol in dimethyl formamide in the presence of sodium ethanolate at room temperature to give the expected sulfide (Equation (19)) <1999CC2007, 2002JPCA3114>. S-(Perfluorooctyl) thioglycoside derivative can be obtained in a similar way under the different reaction conditions (Equation (20)) <1999JFC(98)55>.

Functions Containing Halogens and Any Other Elements

41

p-BrC6H4SH i. NaH, DMF, rt, 1 h n-C8F17I

p -BrC6H4-S-C8F17

ii. DMF, rt, 2 h p-MeC6H4SH NaH, DMF, rt, 24 h

n-C4F9I

p-MeC6H4-S-C4F9

77% p-HOC6H4SH NaH, DMF, rt, 24 h

n-C4F9I

n-C4F9-S-C6H4OH-p

30% p-MeC6H4SH, DBU benzene, rt, 15 h

n-C8F17I

n-C8F17-S-C6H4Me-p

60% PhSH, DBU benzene, rt

n-C8F17I

n-C8F17-S-Ph

50%

Scheme 39

O Et

F F

O F

F I

PriSH, Et3N DMF, 4 h, 30–40 °C

Pri

S O F F

O Et

Et

O

O F

ArSH, Et3N

F I

Et

DMF, 30–40 °C, 4 h

O

S

Ar

O

Ar = N

Scheme 40

n-C6F13I

ArSH, EtONa, DMF, rt, 24 h

ð19Þ

O Ar = O

n-C8F17I

n- C6F13-S-Ar

Pri O

RSH, NaHCO3, Na2S2O4 DMF, H2O, 20 °C, 1.5 h OAc

n-C8F17SR

ð20Þ

O R=

OAc AcO

OAc

Reaction of 1-iodoperfluorobutane with propane-1,3-dithiol occurs under very mild conditions. Both thiol groups react, affording a moderate yield of the corresponding sulfide (Scheme 41) <2000JFC(105)41>.

42

Functions Containing Halogens and Any Other Elements HS n-C4F9I

SH, Na3PO4

n-C4F9S

DMF, 15 min, 20 °C, 45%

SC4F9-n

Scheme 41

1,1-Difluoro-1,3-diiodoheptane in reaction with thiophenol, following its deprotonation by sodium hydride, behaved differently producing an unsaturated sulfide (Equation (21)) <2001JFC(107)89>. I

F

SPh

PhSH, NaH, DMF

I F

F

ð21Þ F

The respective sulfide was produced by the nucleophilic substitution of a bromine atom, in bromodifluoromethyl group attached to benzoxazole moiety, using 2-thiopyridone anion (Equation (22)) <2000JFC(102)369, 2001JFC(109)39>. HS N

N

F

O

F

N

, NaH

Br

N

ð22Þ

S DMF, rt, 23 h

F

O

F

Novel styrene and dimethylisophthalate monomers, with pendant lithium fluoroalkylsulfonate or sulfonimide functional groups and containing perfluoroalkyloxy substituents, were prepared from the corresponding phenolic intermediates. Necessary formation of CF2S fragment was achieved by substitution of bromine atom in a terminal CF2Br group by SO2Na anion (Scheme 42) <2000JFC(105)129>.

p-BrC6H4OCF2CF2Br

Na2S2O4, NaHCO3, DMF H2O, 75 °C, 3 h, 97%

p-BrC6H4OCF2CF2SO2Na

Scheme 42

(iii) From a,a-dichloroalkyl sulfides Dichloroalkyl sulfides are convenient starting materials for the preparation of chlorofluoroalkyl, bromofluoroalkyl, and difluoroalkyl sulfides <1995COFGT(6)35>. Fluorination of dichloroalkyl sulfides containing additional functional groups has been widely studied by Pommelet et al. They described the synthesis of alkylsulfanyldifluoroacetates and ketones by the Halex reaction. The remarkable reactivity of difluorothioacetate derivatives opened rapid access to the preparation of useful building blocks such as gem-difluoroketones and amides (Schemes 43 and 44) (Table 2) <2003TL5061>. Cl

R R'

S

A

R

2SO2Cl2

R'

S

Cl

R

Et3N–3HF

A

R'

Scheme 43 F PhS

F

RM, THF, rt CO2Me

–78 °C, 0.5 h

F R Me H2C= CH H2C= CH-CH2

M

Yield (%)

Li MgBr MgBr

80 70 82

Scheme 44

F

S

A

(b)

(a)

A = CO2Me, COMe, COPh

Cl

PhS

COR F

43

Functions Containing Halogens and Any Other Elements Table 2 Substituents and yields of products depicted in Scheme 43 R0

Product (a) yield (%)

Product (b) yield (%)

CO2Et CO2Me CO2Me CO2Me COPh COMe COMe COPh

52 70 75

70 52 75 80 61 72 68 54

R Ph Bz MeO2CCH2 AcO(CH2)2 Et Bz Ph Ph

70 65

An exchange of chlorine atom in ,-dichlorofluoropentyl benzyl sulfide using antimony pentafluoride in acetonitrile was reported (Scheme 45) <1998ZOR1012>. F

F F Cl

SbF5, MeCN, ∆,1 h

Cl

F

S

F

56%

Ph

F F F Cl

F

F F F F

S

Ph

F F F F

Scheme 45

(iv) From tri- or tetrahalomethanes Only a few examples of substitution of a chlorine atom in chlorodifluoromethane by thiols, using a variety of conditions, have been reported in <1995COFGT(6)35>. A mechanism of the substitution had been under discussion pointing to both a carbene and SN2 type character. Since then many new syntheses of dihaloalkyl sulfides have been published. Such methane derivatives like difluorodiiodomethane, chlorodifluoromethane, trifluoro-, and trichloromethanes were applied as starting materials. It appears from these reports that the carbene mechanism predominates. The treatment of difluorodiiodomethane with thiophenol in the presence of sodium hydride affords difluoromethyl phenyl sulfide in a low yield (Equation (23)) <2000JFC(102)105>. F F

I

PhSH, NaH, DMF, 20 °C

F

12%

F

I

SPh

ð23Þ

The majority of reported syntheses starts from chlorodifluoromethane. A high yield of the respective sulfide is obtained while treating chlorodifluoromethane with ethoxycarbonylmethylthiol in the presence of sodium ethanolate in ethanol (Scheme 46) <2000CPB509>. Also thiophenol reacts smoothly with chlorodifluoromethane, this time in the presence of sodium hydroxide in aqueous dioxane (Scheme 47) <1996IZV(45)162>. EtOCOCH2SH, EtONa F Cl F

EtOH, 1 h, heat

F

80%

F

SCH2CO2Et

Scheme 46

F Cl F

ArSH, NaOH dioxane, H2O, 45 °C, 3.3 h

F

89%

F

Ar = C6F5

Scheme 47

SAr

44

Functions Containing Halogens and Any Other Elements

Heteroaromatic thiols can substitute a chlorine atom in chlorodifluoromethane. An example of this type of reaction is reported to give the respective sulfide in a low yield (Scheme 48) <2001JFC(108)211>. A similar method was used for the preparation of a sulfide containing, beside difluoromethyl group, a large chiral substituent (Equation (24)) <1998JAN374>.

ArSH, KOH, DMF F Cl

DMF, 50–120 °C, 5 min

F

24%

F

F

SAr

N

Ar =

N

EtO

Scheme 48

F

F

RSH

Cl

SR

F

F Si O

ð24Þ SH N

RSH = O

O

C6H4NO2-p

Another enlarged substituent was introduced into a prepared sulfide in the presence of potassium t-butoxide. The reaction was carried out in tetrahydrofuran (Equation (25)) <1996JMC757>. F Cl

RSH, t-BuOK, THF, 0 °C, 30 min

F SR

F

F O

SH RSH =

ð25Þ

O

H

O

H O

Only one example of sulfide formation starting from trifluoromethane has been found. Dioctyl disulfide was used in the reaction as a precursor of an attacking S-nucleophile (Scheme 49) <2000JOC8848>.

n-C8H17SSC8H17-n

F F F

Me3SiSiMe3, DMF, THF

F n-C8H17S

F

–15 to –20 °C, 17.5 h 45%

Scheme 49

Also only one example of synthesis of sulfides starting from trichloromethane has been spotted. The reaction was performed under PTC conditions and doubtlessly followed the carbene mechanism resulting in insertion of dichloromethylene between sulfur atom and vinyl group (Scheme 50) <2000CHE201>.

45

Functions Containing Halogens and Any Other Elements H N

H N

S

Cl

N

Cl Cl

Cl

Cl

S

TBAB, NaOH aq. 50% 45–55 °C, 25 h 21%

N

Scheme 50

(v) From thioformates, thioesters, and ortho-trithioesters COFGT (1995) <1995COFGT(6)35> has brought only examples of dichlorination of alkyl thioformates yielding alkyl dichloromethyl sulfides. Since then several new approaches to the synthesis of dihaloalkyl sulfides have been designed starting with dithioesters or ortho-trithioesters. (a) From dithioesters. Thiocarbonyl group in dithioesters can be exchanged by difluoremethylene moiety using mercury(II) fluoride–potassium fluoride mixture in tetrahydrofuran in the presence of pyridinium hydrogen fluoride (Equation (26)) <1996TL3223>. S Ph

F F

HgF2, KF, THF S

HF–pyridine

Ph

ð26Þ

S

Similar results (the exchange of sulfur atom by two fluorine atoms) were achieved using tetrabutylammonium–hydrogen fluoride complex in the presence of N-iodosuccinimide (Scheme 51) <1999BCJ805> or by treating dithioester with bis(2-methoxyethyl)aminosulfur trifluoride in the presence of antimony(III) fluoride (Scheme 51) <2000JOC4830>. N-iodosuccinimide, Bu4n N–H2F3, CH2Cl 2

S p-Ph-C6H4

S

F p-Ph-C6H4

F S

86%

F

S S

N-iodosuccinimide,

Bu4nN–H2F3,

CH2Cl2

F S

52%

p-(t-Bu)C6H4

S

bis(2-methoxyethyl)aminosulfur trifluoride

S

SbCl3, CH2Cl2, 20 °C,1 h 74%

F p-(t-Bu)C6H4

F S

Scheme 51

(b) From ortho-trithioesters. In 1998, Japanese chemists published two papers on synthesis of ,-difluoroalkyl sulfides from ortho-trithioesters. The use of Et2SF3 led to the formation of the desired sulfide in a very low yield <1998BCJ2687>. In contrast to that, the same authors achieved very good results of difluorination, applying tetrabutylammonium–hydrogen fluoride complex in the presence of 1,3-dibromo-5,5-dimethylhydantoin (Scheme 52) <1998BCJ1939>.

(vi) From alkenes The first report on synthesis of dichloroalkyl sulfides via chloroalkenes was probably published in 1958. Since then additions of thiols or disulfides to alkenes have been reported several times <1995COFGT(6)35>. In the last few years haloalkenes became rather common substrates in syntheses of dihaloalkyl sulfides. Several haloalkenes such as tetrafluoroethene, chlorotrifluoroethene, alkoxytrifluoroethene, 1,1,2-trifluoroalkenes, 1,1-dichloro-2,2-difluoroethene, and 1,1-difluorethene were used in reactions with thiols, disulfides, or other sulfur compounds to yield difluoroalkyl sulfides.

46

Functions Containing Halogens and Any Other Elements S

Ph

F

Ph

Et2NSF3, CH2Cl2, 0 °C, 10 min

S S

13%

O

OH

S

Ph

F

Ph

Bu4N–H2F3, i. CH2Cl2, 10 min

S S

S F

51%

S F

O

O F S Ph

S Ph

Bu4N–H2F3, i. CH2Cl2, 20 min

S S

79%

S O

F Ph

51%

OH Ph

Br

Bu4N–H2F3, i. CH2Cl2, 10 min

S S

S F

O F

Ph

Bu4N–H2F3, i. CH2Cl2, 10 min

S S

S F

Ph

O

62%

S F

F

i = 1,3-dibromo-5,5-dimethylhydantoin

Scheme 52

Reaction of tetrafluoroethene with sulfur chloride leads to the formation of mixtures of compounds in proportions depending on the conditions used. One of the products is shown in Equation (27) <2001JFC(112)325>. F F

F F

S2Cl2, HF, BF3 40 °C, 12 h

F F F

F S

S

Cl

ð27Þ

F and others

Irradiated 1,1,2-trifluoro-1,4-pentadiene reacts smoothly with mercaptoacetic acid. A high yield of the addition of two molecules of the nucleophile to both double bonds is observed. When the reaction is conducted in the presence of azobisisobutylnitrile, an initiator of a radical process, the yield drops down (Scheme 53) <1998JFC(92)77>.

F

F

F F

O

F F

F

F

HO2CCH2SH, MeCN, PhCOPh

O

irradiation, 81%

HO

S

S

O

F F

HO2CCH2SH, AIBN, MeCN

O

80 °C, 7 h, 37%

HO

S

OH

S

OH

Scheme 53

Sodium thiophenolate is added easily though slowly to chlorotrifluoroethene in ethanol affording 2-chloro-1,1,2-trifluoroethyl phenyl sulfide <1997T17127, 1998TL6529>. At higher temperatures the reaction proceeds faster without affecting a yield (Scheme 54) <2000T3539>. Products distribution in reactions between chlorotrifluoroethene, 1,1-difluoroethene and ethylene thioglycol has been studied in detail. One of the major products is 2-chloro-1,1,2,4,4pentafluorobutyl 20 -hydroxyethyl sulfide (Scheme 55) <1995JFC(74)37>.

47

Functions Containing Halogens and Any Other Elements F

F

PhSNa, EtOH, 15 h

F

Cl

76%

F

F

F

F F Ph

Cl

S F

F F

PhSH, NaOH, 120 °C, 6 h

Ph

85%

Cl

Cl

S F

Scheme 54

F HOCH2CH2SH, Bz2O2

F F

F F HO

F

S

MeCN, 80 °C, 4 h

Cl

F

F Cl

F

Scheme 55

Chlorotrifluoroethene forms the respective chlorotrifluoroethyl phenyl sulfide in reaction with diphenyl disulfide under electrochemical conditions. The yield of the product is reasonable (Equation (28)) <1998CCC378>. F

F

F

Cl

F F

PhSSPh, MeCN Electrolysis, 30%

Ph

Cl

S

ð28Þ

F

Fluorosulfonic acid and sulfur dichloride reacting with trifluoromethyl trifluorovinyl ether yield a product containing fragments of both reagents added to the double bond in the starting ether (Equation (29)) <1996IZV(7)1745>. F F F

SCl2, HSO3F, 30–35 °C

F F

F

O

32.5%

F F

F

O

S O O F O F

S

Cl

ð29Þ

F F

Several new examples of addition of thiols to 1,1-dichloro-2,2-difluoroethene have been reported. The reaction is highly regiospecific, leading to the formation of ,-difluoro,-dichloroethyl sulfides usually in very good yields (Scheme 56) <1995JFC(73)27, 2000T3539>. When N-(t-butylcarboxy)-2-thiopyridone (instead of a thiole) is added to dichlorodifluoroethene, the reaction of addition is accompanied by migration of the N-substituent, and ,-difluoro-,-difluoroalkyl 2-pyridyl sulfides are obtained (Scheme 57) <1992TL3491, 1995T1903, 1997JOC7192>.

F

Cl

n-C6F13CH2CH2SH, MeCN

F

Cl

Butperpivalate, 70 °C, 4 h

F

Cl

PhSH, NaOH, 120 °C, 8 h

F

Cl

90%

Cl n-C6F13CH2CH2S

Cl Cl

Ph S F F

Scheme 56

Cl F F

48

Functions Containing Halogens and Any Other Elements F F

N Cl

i. MeCN, irr.

Cl

52%

Cl N

i=

O S

Cl But

S F

F

O But

F

Cl

i. CH2Cl2, irr. 5 h

F

Cl

35%

N Cl Cl S F F

i=

N

O O

S

Scheme 57

Novel sulfides, sulfones, and fluorovinyl ethers were prepared using tetrafluoroethylene as the only fluorinated substrate. Addition of thiole sodium salts and carbon dioxide to tetrafluoroethylene, followed by dimethylsulfate, provided corresponding methyl sulfide-esters. Reduction of the sulfide-esters by sodium borohydride gave sulfide-alcohols. Oxidation of the sulfide-esters with HOF in acetonitrile resulted in the formation of the corresponding sulfone-esters. Conversion of the sulfide-alcohols to their sodium salts with sodium hydride in diglyme, followed by the addition to tetrafluoroethylene, provided sulfidetrifluorovinyl ethers. The latter readily co-polymerized with tetrafluoroethylene to give higher molecular weight co-polymers (Scheme 58) <1999JFC(93)93>.

O F F R S O F F

HOF MeCN, 80%

F F

F F

F F

i. RSNa, CO2, DMSO ii. (MeO) 2SO2

F F

R = Me R = But F F

OH

RS F F

ii. F2C=CF2

O

EtOH

F F RS

O F F

NaBH4

80% 84%

i. NaH, diglyme R = Me, But

O

R S

O

OH

R S F F >90% >90%

OCF=CF2

F F ~60%

Scheme 58

(vii) From carbon disulfide Elemental fluorine reacting with carbon disulfide at 120 C affords fluorinated sulfide. No further advances have occurred in this area since the work of Shimp and Lagov <1977IC2974> cited in <1995COFGT(6)35>.

(viii) From a-fluoroalkyl sulfoxides One example of Pummerer-type reaction was reported in <1995COFGT(6)35>. No further advances have occurred in this field since that publication.

49

Functions Containing Halogens and Any Other Elements (ix) From perfluoroalkanecarboxylic acid salts

Diphenyl disulfides react with potassium salts of perfluoroalkanecarboxylic acids at elevated temperatures affording moderate yields of perfluoroalkyl phenyl sulfides (Scheme 59) <2001JFC(107)311>.

n-C3F7COOK

PhSSPh, DMF, 130 °C, 6 h

PhSC3F7-n

29% C2F5COOK

PhSSPh, DMF, 145 °C, 5 h

PhSC2F5

42%

Scheme 59

6.02.1.2.2

Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function (R1CHal2SR2)

Thiolate additions to mixed chlorofluoroalkenes under radical, ionic, or electrochemical conditions were employed to prepare mixed dihaloalkyl sulfides <1995COFGT(6)35>. As one can see from examples shown here (in equations and schemes), the reactions used resemble those described in the former section of this chapter. Fluorination of chloroalkyl sulfide has been reported too (Equation (30)) <1995JOC3459>. Et3N–3HF, MeCN, 20 °C

Cl Ph S

Cl F Ph S

Electrolysis, 66%

CO2Et

ð30Þ CO2Et

Pommelet et al. elaborated several reactions leading to mixed dihaloalkyl sulfides (Scheme 60) <1996TL2413>. Particularly interesting is the practically quantitative, highly regiospecific chlorination of methyl esters of -alkylthio--fluoroacetic acid, using sulfuryl dichloride. R S

2SO2Cl2

R

CO2Me

Cl

Cl

PH2F3

S

A

CCl4

R

Cl

F

S

A

R = Ph 42%, Me 37%, CO2Me 75% F

R S

2SO2Cl2

R

ca. 100%

CO2Me

Cl

F

S

A

R = Ph, Me, CO2Me F O O

O

S O

SbCl3, DAST, rt, 2–3 d

O

O

F Cl O

S O

O

S O

F O

O

SO2Cl2

O O

O

O

S O

Scheme 60

-Chlorinated--fluorinated sulfides were synthesized in good yields by the nucleophilic fluorination of the corresponding dichlorinated sulfides, formed in the first step of the reaction. It can be achieved with Et3N-3HF in refluxing acetonitrile. A number of examples are given in the scheme-explaining table (Scheme 37, Table 1) <1997T12565>. Addition of cysteine N-acetyl derivative to 1,2-dichloro-1,2-difluoroethene in the presence of sodium amide at 50 C occurred without racemization (Equation (31)) <1996MI1092>.

50

Functions Containing Halogens and Any Other Elements

F Cl

F Cl

RSH, NaNH2, liq. NH3, –50 °C

AcHN

CO2H H

F Cl

S CO2H RSH = AcHN H

F

Cl

ð31Þ

SH

6.02.1.2.3

Tetracoordinated carbon atoms bearing one halogen and two sulfur functions (R1CHal(SR2)2)

No further advances in the field of the title compounds synthesis have occurred since the publication of COFGT (1995) <1995COFGT(6)35>. Only an interesting transformation of a compound of this class was reported (Equation (32)) <1996CB1383>. Me3SiCl, 50 °C, 6 h (F3CS)2CBrCO2H

6.02.1.3 6.02.1.3.1

83%

(F3CS)2CBrCO2SiMe3

ð32Þ

Halogen and Se or Te Derivatives (R1CHal2SeR2 or R1CHal2TeR2) Tetracoordinated carbon atoms bearing two halogens and one selenium function (R1CHal2SeR2)

Several examples of compounds of the type reviewed in this section have been reported. Their preparation often involves transmetallation reactions of metal selenyl dihalomethyl derivatives. Also numerous examples of organoselenium metal complexes are known. In some cases almost quantitative yields of the products are obtained. Sometimes mixtures of organoselenium compounds are produced and neither the conditions of reactions nor yields are provided <1995COFGT(6)35>. Some advances that have occurred in this field since the publication of COFGT (1995) are presented here.

(i) From difluoroiodoalkane, bromodifluoroalkane, or chlorodifluoroalkane derivatives Twelve years ago Uneyama and Kitagawa reported shortly that butylphenyl selenide together with other products can be obtained by reaction of (nanofluorobutyl)iodide with diphenyl diselenide (Equation (33)) <1991TL375>. Ten years later the same method, under modified conditions, was applied for the preparation of perfluoroalkyl phenyl selenides in high yields (Scheme 61) <2001SL1260>.

C4F9I

NaBH4, PhSeSePh, EtOH, 0 °C, 15 min

C4F9SePh

rt, 2 h, 1-hexene

n-C4F9I

PhSeSePh, NaO2SCH2OH, DMF, H2O, 20 °C

n-C4F9SePh

57% n-C8F17I

MeSeSeMe, NaO2SCH2OH, DMF, H2O, 20 °C 79%

Scheme 61

n-C8F17SeMe

ð33Þ

51

Functions Containing Halogens and Any Other Elements

Bis(Pentafluoroethyl)selenide has also been formed from pentafluoroethyl iodide and selenium in the presence of copper metal (Equation (34)) <2000JFC(102)301>. C2F5I

Se, Cu, 220–230 °C, 15 h

ð34Þ

C2F5SeC2F5

Irradiation of mixtures of -chloro-,-difluorotoluene with sodium arylselenolates in dimethyl formamide results in the formation of aryl ,-difluorobenzyl selenium (Scheme 62) <1996BCJ2019>.

F

F

ArSeNa, EtOH, DMF, 100 °C

Ph

Cl

Ph

Irradiation

F

Se Ar F

Ar = Phenyl, 89%; naphthyl, 84%

Scheme 62

Reaction of N-allyl bromodifluoroacetamide with bis(phenyl)diselenide results in the substitution of a bromine atom by phenyl selenide group (Equation (35)) <1997TL7763>. O N H

O

PhSeSePh, NaBH4, THF, EtOH, 0 °C, 3 h

F Br

45%

F

F

N H

Se Ph

ð35Þ

F

(ii) From 1,1-difluoroalkene derivatives Chlorotrifluoroethene reacting with bis(phenyl)diselenide in acetonitrile under electrochemical conditions affords 2-chloro-1,1,2-trifluoroethyl phenyl selenide in a good yield (Equation (36)) <1998CCC378>. F

F

F

PhSeSePh, MeCN, electrolysis 57%

Cl

F

F

F

Cl

ð36Þ

Ph Se

Selenium compounds can be added to the double bond of 1,1-difluoroethene derivatives bearing a variety of additional substituents (Scheme 63) <2000TL7893, 2002CEJ2917>. EtO2C

F

p-MeOC6H4 N F SiMe3

EtO2C

F

p-MeOC6H4 N

F

PhSeF, CH2Cl2, –78 °C 64%

SePh

O

O F

N Ph

N

F

F

i. PhSeCl, TfOSiMe 3, hexane, THF, 20 h ii. H2O, hexane, THF, 1 h, 60%

N Ph

N

Se Ph F

Scheme 63

A mixture of reduced products containing ,-difluoromethyleneselenium moiety is obtained in the reaction of difluoromethyl phenyl selenoxide with dimethyl sulfide and acetic anhydride in dichloromethane. Similar reductions, unfortunately also leading to very low yields of difluoromethyl phenyl selenide, are observed in reactions of the selenoxide with mixtures of e.g., BuOBuAc2O, MeOCH2CH2OMeAc2O, (CH2)3OAc2O, (CH2)5OAc2O, etc. (Scheme 64) <1995JOC370>.

52

Functions Containing Halogens and Any Other Elements O Ph Se

F F

O Ph Se

F F

SMe2, Ac2O, CH2Cl2, ∆, 4 h

F Ph Se

6%

SMe2, Ac2O, CH2Cl2, ∆, 4 h

F F Ph Se

29%

S F

Scheme 64

6.02.1.3.2

Tetracoordinated carbon atoms bearing two halogens and one tellurium function (R1CHal2TeR2)

Among compounds described in this section only perfluoroalkyl tellurides and additionally ditellurides have been well known for more than ten years. Other compounds of this class have hardly been reported and without details of their preparation or yields obtained. The 1990s have brought about more details concerning preparations of difluoroalkyl tellurides. A general route to these compounds involves the reaction of dialkyl tellurides with bis(trifluoromethyl) cadmium or trifluoromethylzinc bromide performed in the presence of acetonitrile and boron trifluoride <1995COFGT(6)35>. Some advances that recently have occurred in this area are presented here. Unfortunately, the examples concern only syntheses of perfluoroalkyl derivatives of tellurium. Bis(pentafluoroethyl)telluride was obtained by the treatment of pentafluoroiodoethane with tellurium in the presence of copper metal at a very low pressure and an elevated temperature. Bis(pentafluoroethyl)ditellurid was prepared in a high yield under similar conditions using bis(pentafluoroethyl)mercury as the starting material (Scheme 65) <1996JCS(D)4463>.

C2F5I

Te, Cu,180 °C,36 h, 0.01 torr

C2F5TeC2F5

68% C2F5HgC2F5

Te, Cu, 200 °C, 15 h

C2F5TeTeC2F5

85%

Scheme 65

UV-irradiated bis(pentafluoroethyl)telluride is transformed into bis(pentafluoroethyl)ditelluride, which on treatment with silver cyanide gives (pentafluoroethyl)tellurium cyanide and with molecular iodine at low temperature yields (pentafluoroethyl)tellurium iodide (Scheme 66) <2000JCS(D)11>.

n-C3F7TeC3F7-n

Furan, 20 °C, 16 h, UV

n-C3F7TeTeC3F7-n

73% AgCN, 22 °C

n-C3F7TeTeC3F7-n

n-C3F7TeTeC3F7-n

92% I2, CHCl3, –196 to –20 °C

n-C3F7TeC N

n-C3F7TeI

100%

Scheme 66

6.02.1.4

Halogen and Mixed Chalcogen Derivatives (R1CHal(OR2)(SR3))

These compounds have been practically excluded from this section because the system is almost exclusively present in heterocycles, e.g., in oxathiolium salts covered by other reviews. Here only a couple of examples of compounds that can be described by the formula (R1CHal(OR2) (SR3)) are given.

53

Functions Containing Halogens and Any Other Elements

In 1995 Chande and Joshi published two papers describing bromination of extended ethanone derivatives, bearing C-, O-, S-linked large substituents and a hydrogen atom at the -carbon atom. Solutions of the starting material and molecular bromine in glacial acetic acid, when subjected to ultraviolet irradiation, afford products. Yields of the bromination products, depending on substituents in a substrate, vary from 50% to 95% (Scheme 67) <1995IJC(B)54, 1995IJC(B)147>.

Ph

O

N N

C6H4Cl-p Br2, MeCO2H, hν

S

N Ph N

N Ph N

O

N N

S

O C6H4Cl-p

C6H4Me-p O C6H4Cl-p

N N

Ph

S

O C6H4Cl-p

Br2, MeCO2H, hν

Br O C6H4Cl-p

O

N N

Ph

C6H4Me-p

H

90%

H

Br O C6H4Cl-p

H

S

N N

C6H4Cl-p

S

O

N N

90%

C6H4Me-p

O

N N

Ph

H

H

N Ph N

Ph S

50%

Br2, MeCO2H, hν S

O

N N

N N

C6H4Me-p Br O C6H4Cl-p

S H

Br2, MeCO2H, hν N N o-HOC6H4

N Ph N

O S

C6H4Me-p

95%

N N o-HOC6H4

O C6H4Cl-p

H

N Ph N

O S

H

C6H4Me-p Br O C6H4Cl-p

Scheme 67

6.02.2

FUNCTIONS CONTAINING HALOGEN AND A GROUP 15 ELEMENT AND POSSIBLY A CHALCOGEN

6.02.2.1

Halogen and Nitrogen Derivatives: General Considerations

Compounds of this class are somewhat unstable, being in equilibrium with the corresponding isomeric haloiminium salts. The equilibrium between isomeric forms depends on N-substituents. Electron-withdrawing substituents shift the equilibrium to haloalkylamines. This dynamic balance has been discussed in several papers and reviews <1995COFGT(6)35>.

6.02.2.1.1

Tetracoordinated carbon atoms bearing two halogens and one nitrogen function

Similar to COFGT (1995) <1995COFGT(6)35>, examples described here refer to compounds for which the equilibrium is probably shifted to covalent species. Probably the first compound reported as N-(dichloromethyl)-N,N-dimethylamine in US patent in 1955 did not satisfy these requirements <1955USP2854458>.

(i) From imines The addition of dihalocarbenes to imines was and still is a route of choice for synthesis of heterocycles like 2,2-dihaloaziridines. No further advances have been noticed in this field since the publication of COFGT (1995) <1995COFGT(6)35>.

54

Functions Containing Halogens and Any Other Elements

(ii) From amines or hydroxylamines Several halogenation methods have been applied to tertiary or secondary amines or alkylamino derivatives of other compounds. Only some of the routes lead to high yields of aminodihaloalkyl products. Just as superior fluorination involves the use of sulfur tetrafluoride, chlorination involves the use of molecular chlorine. The methods can be applied to perhalogenation of both tertiary and secondary amines. In the latter case the halogen atom also replaces N-hydrogen <1995COFGT(6)35>. Molecular fluorine was used for perfluorination of triethylamine at a low temperature (Equation (37)) <1999JFC(94)157>. F2, –35 to –20 °C, 14 h

Et3N

ð37Þ

(F3CF2C)3N

Some other methods sporadically give satisfying results. Displacement of chlorine by fluorine atoms is an effective approach to (difluoroalkyl)amino compounds. Using hydrogen fluoride in pentane at a low temperature allows replacement of four chlorine atoms by fluorine ones in N,N-di(dichloromethyl)aniline (Equation (38)) <1996JFC(76)95>. Cl Ph N

F Cl Cl

HF, pentane, –30 to –5 °C

F

Ph N 79%

ð38Þ

F

Cl

F

An unusual N-perfluoroalkylation of O-benzoyl sec-butylhydroxylamine, using bis-heptafluorobutyryl peroxide in perhalogenated ethane, leading to the formation of the corresponding amineoxy free radical, has recently been reported (Equation (39)) <2002JFC(116)109>.

N

O Bz

(C3F7CO2)2, Cl2FCCClF2

O N C3F7-n

20 °C

H

ð39Þ

A common electrochemical approach usually affords mixtures difficult to separate and leads to low yields of the desired compounds. Some exceptions to this general rule are known. While fluorination of N-ethyl-N-isopropyl amine under electrochemical conditions leads to a very low yield of the corresponding perfluorinated compound, N-(n-butyl)-N-methylamine under similar conditions affords a high yield of its perfluorinated derivative (Scheme 68) <2000JFC(106)35>. The same authors have reported moderate yields of perfluorinated products in electrochemical syntheses of other compounds too. An example is given (Equation (40)) <2001JFC(108)215>.

F H N

F F F F N F F F F

HF, 7–8 °C, 390 min, electrolysis 2.4%

H N

F

HF, 7–8 °C, 434 min, electrolysis

F

F F

F

F N

F F

high yield

F

F

F

F

F F F

Scheme 68

O

O N N

O

O

HF, 7–8 °C, 10 h, electrolysis 50%

F

F

F FF F O

N

F F

F

F F F

F

F F

ð40Þ

55

Functions Containing Halogens and Any Other Elements

As it was mentioned before, electrochemical methods usually afford mixtures. Low yields of fluorinated products are determined by chromatography. This can also be found out from the following schemes. Often yields are not reported at all and detailed synthetic procedures are not disclosed. Examples are given in Scheme 69 <1999JFC(97)229, 1999JFC(99)51, 2001JFC(108)21> and Scheme 70 <1996JCS(P1)915, 1997JFC(82)143, 1997JFC(83)1, 2002JFC(115)21>. OH

N

(C2F5)2N

8.7% (chromat.)

N H

N

F

F F

O

HF, 7–8 °C, 521 min, electrolysis

Si O

(F3C)2N

8.1%

F

F F

OH

N

HO

O

HF, 7–8 °C, 616 min, electrolysis

O

HF, 7–8 °C, 637 min, electrolysis

(C2F5)2N

5.9%

N

F

F F

Scheme 69

O O HF, electrolysis O

N

F F

F F

F

Not separated

F

N F

HF, electrolysis

N

F

F F F F

F

F F

F

n-C3F7N(C2F5)2

F N

HF, 0 °C, 24 h

N

Electrolysis

(F3C)3N

HF, electrolysis (n-C3H7)3N

(n-C3F7)3N

N HF, electrolysis N(C2F5)3

N

Scheme 70

(iii) From amides and thioamides Many of the compounds of this class have been prepared where electron-withdrawing groups limit the possibility of salt formation. A variety of approaches were successfully used in these cases for conversions of amides and thioamides. Some advances that have occurred in this area since the publication of <1995COFGT(6)35> are reported here. N,N-Dimethyl-,-difluorobenzylamine was prepared in a good yield from N,N-dimethylbenzthioamide by its fluorination with bis(2-methoxyethyl)aminosulfur trifluoride in the presence of antimonium trichloride (Scheme 71) <2000JOC4830>.

56

Functions Containing Halogens and Any Other Elements bis(2-methoxyethyl)aminosulfur trifluoride S

F

SbCl3, CH2Cl2, 20 °C, 48 h

Ph N

Ph

N

78%

F

Scheme 71

Very high yields of N,N-di(dichloromethyl)aniline and its p-chloro derivative are obtained from the corresponding N,N-diformylanilines while treating them with phosphorus pentachloride– phosphorus oxychloride mixture (Scheme 72) <1996JFC(76)95>.

O O

Ph N

Cl

PCl5, POCl3, 80 °C, 2 h

Cl

Ph N

92%

Cl Cl Cl

O O

p-Cl-C6H4-N

PCl5, POCl3, 80 °C, 2 h

p-Cl-C6H4-N

94%

Cl Cl

Cl

Scheme 72

The last decade has produced several examples of synthesis of N-(dihaloalkyl)sulfonamides from sulfonamides. The sulfonyl group obviously stabilizes the products. Cobalt trifluoride at a high temperature allows the displacement of four hydrogen atoms by fluorine ones in N,N-dimethylamide of fluorosulfonic acid (Equation (41)) <1995JFC(74)181>.

O F S N O

F O F F S N F O F

CoF3, 200–250 °C 38.5%

ð41Þ

Fluorination of N,N-dimethylamide of trifluoromethanesulfonic acid under electrochemical conditions affords the corresponding, additionally tetrafluorinated, sulfonamide in low to moderate yields. Other examples of halogenation under electrochemical conditions of either sulfonamides or amides were also reported (Scheme 73) <1995JFC(75)157, 1998JFC(87)157, 1997JFC(81)115, 2002JFC(113)201>.

F F F

O S N O

HF, electrolysis 27%

F O F S N F O F

F F F

F O F O N S S N O F O

HF, 0 °C, electrolysis

F F

F O F O F N S S N F O F O F F O

O n-C3F7

HF, –15 °C, electrolysis

F

n-C3F7 N

F

F

N

F

Scheme 73

57

Functions Containing Halogens and Any Other Elements

N-Alkylation of sulfonamide sodium salt by bromodifluoroalkene is another approach to the synthesis of an N-(,-difluoroalkyl)sulfonamide (Equation (42)) <2000CPB885>. The displacement of a sulfur atom by two fluorine ones in thioamide is shown in Equation (43) <1998SL1243>. F (PhNSO2Me)

F

Na

Br , Pd(OAc)2, PPh3, THF, 40 °C, 2 h

F F

S n-C7F15

F F

NBS, PPHF, CH2Cl2, 1 h

n-C7F15

N

Ph N

ð42Þ

SO2 Me

ð43Þ

N

(iv) From acyl halides Treatment of acyl fluorides with tetrafluorohydrazine under photolytic conditions resulting in the formation of corresponding perfluoroaminoalkane was reported earlier <1995COFGT(6)35>. A perhalogenated tertiary amine, containing apart from fluoro-substituents, one iodo-atom in -position was prepared by Abe et al. from the appropriate acyl fluoride by treating it with lithium iodide at an elevated temperature (Equation (44)) <1997JFC(83)117>. F (F3C)2N

F F O

F

F

LiI, 180 °C, 7.3 h

F

(F3C)2N

63%

F

F

ð44Þ

I

F

(v) From nitriles Chlorofluorination of primary alkyl cyanides, bearing electron-withdrawing groups, is a mild and convenient route for the preparation of N,N-dichloro- or N-chloro-N-fluoro-, -difluoroalkylamines. Yields are excellent. Other methods of synthesis of compounds of this class were also reported, being applied to particular cases <1995COFGT(6)35>. The treatment of acetonitrile with hydrogen bromide for 12 days has afforded N-(,-dibromoethyl)-acetamidine, probably as the result of electrophilic addition of two molecules of hydrogen bromide to cyano group, followed by nucleophilic addition of the intermediate dibromoethylamine to another molecule of acetonitrile (Equation (45)) <1998IZV(11)2274>.

N

HBr, 12 days

H N

Br

NH

ð45Þ

Br

Hydrogen fluoride is added to the double NS bond in a tetrafluorinated derivative of acetonitrile leaving the triple CN bond intact (Equation (46)) <1995CC1437>. F F F S N F N N H i = tris(dimethylamino)sulfonium difluorotrimethylsilicate F

F F S N F

i

F

ð46Þ

(vi) From haloiminium salts Haloiminium salts, by treating them with hydrogen halides at a low temperature, are easily converted to dihaloiminium species staying in equilibrium with dihaloalkylamines. Nothing is to be added since the publication of <1995COFGT(6)35>.

58

Functions Containing Halogens and Any Other Elements

(vii) From haloalkenes and haloalkanes The addition of secondary amines to perhalogenated ethenes results in the formation of the corresponding N,N-dialkyl-N-(tetrahalogenoethyl)amines <1995JFC(73)267, 1998JCR(M)301>. In a similar way, though under photochemical conditions, N-iodo derivatives of secondary amines react. The iodine atom is present in the products. Other, less general methods, were reported too in COFGT (1995) <1995COFGT(6)35>. Since then some new examples of known methods and new approaches to the synthesis of dihaloalkylamines from haloalkenes have been reported. For example: tetrafluoroethene reacts slowly with dimethylamine at room temperature to afford dimethyl-tetrafluoroethylamine in 90% yield (Equation (47)) <2001JFC(109)25>. F

F

F

Me2NH, 20 °C, 12 h

F

F

F

98%

F

F

ð47Þ

N

Secondary amines like diethylamine and di(n-butyl)amine are easily added to the double bond in an unsaturated perfluorated expanded diether in tetrahydrofuran at room temperature. Also in these cases yields of the addition products are high (Scheme 74) <1999ZPK(72)1345, 2000JFC(106)13>.

F F F F

O F

F F F

F F F F

O F

F F F

F

F F F F

O

F F

67%

F

F

F F

Et2NH, THF, 20 °C

O F F F

F

F

F

F F F F

O F

F F

82%

NEt2

F

F F F

F

F F

F

O F

F F F O

F F

Bun2NH, THF, 20 °C

F

F

F

F F F

F

O F

F

N(Bun)2

F

Scheme 74

Tetrafluoroethene reacting at 400 C with nitrogen trifluoride in the presence of caesium fluoride gave perfluorinated ethylamine in 10% yield only (Equation (48)) <2000JFC(101)15>. F

F

F

F

NF3, CsF, 400 °C, 1.5 h 10%

F F F

F N

F

ð48Þ

F F

A rather unexpected product was obtained from the reaction of partly fluorinated unsaturated tertiary amine with molecular fluorine. The reaction yielded a product, in which fluorine atoms displaced all hydrogen atoms in saturated N-alkyl groups while the former double bond was saturated by addition of two hydrogen atoms or stayed intact. No yield was given (Equation (49)) <1996JFC(76)139>. C2F5CF3 (F3C)2C-C NEt2 F F

F2

C2F5CF3 (F3C)2C-C N(C2F5)2 F F F

.

ð49Þ

Perhaloalkanes bearing an iodine atom in one terminal position react with nitrosobutane to yield the corresponding N-perhaloalkyl-N-(t-butyl)amineoxy free radicals (Scheme 75) <1995JFC(75)1>. N-(,-Difluoroalkyl)-N-(t-butyl)amineoxy free radical was also produced in the reaction of nitrosobutane with methoxycarbonyldifluoromethylsulfonyl azide (Equation (50)) <1995JFC(73)175>.

59

Functions Containing Halogens and Any Other Elements

F Cl F

ButNO, (NH4)2Ce(NO3)6, NaHSO3

F

aq. sulfonic acid, MeCN, H2O

F Cl F

F

F F F F Cl

I

I

ButNO, NaHCO3

F

Rongalite, DMF, H2O

F F F

O N Bu-t F

F

F F F F Cl

O N Bu-t F

F F F

Scheme 75

O

O

MeO2CCF2SO2N3

N

O N

O

CH2Cl2

ð50Þ

F F

Zhou et al. also reported other self-spin-probing reactions, in which products contained N-(,-difluoromethylene)amineoxy free radical grouping (Scheme 76) <1999JFC(98)61, 1986JA3132, 1999T2263>. (C2F5CO2)2, 20 °C NO2

C2F5

F2ClC–CFCl2

Na

C2F5NO2, CH2Cl2, (C2F5)2NO

N O

N O

N

NO2

.

O N C2F5

Cl2FCCFCl2

O

Scheme 76

(viii) Routes specific to dihalonitroalkanes and dihalonitrosoalkanes Jones and Matthews in their review <1995COFGT(6)35> describing routes to dihalonitroalkanes divided them into three approaches depending on the starting materials such as nitromethanes, haloalkenes, and nitro alcohols and gave examples of each approach. No further advances have been noted in this field since that publication. Indeed, treating of diazomethane with sodium hypochlorite afforded dichloronitromethane, but no yield was given (Equation (51)) <1998MI(32)3935>. H2C N N

NaOCl

Cl

H2O

Cl

NO2

ð51Þ

Halogenonitrosoalkanes were not reported in <1995COFGT(6)35>. The only example of a compound of this class found by the authors was reported in 1995. Perfluoronitrosopropane was obtained in a very high yield from 1,2-dimethoxyethane in reaction with bis(perfluoropropyl)cadmium and NOCl (Equation (52)) <1995JFC(73)273>. O

6.02.2.1.2

O

NOCl, (C3F7)2Cd

C3F7NO

ð52Þ

90%

Tetracoordinated carbon atoms bearing one halogen and two nitrogen functions

When the nitrogen functions are amino groups, compounds of this class are unstable and all attempts to prepare them end in the formation of corresponding haloiminium salts. Exceptions are halodiazirines. Many examples of synthesis of these compounds have recently been reported. All the examples employ amidines as starting materials. Yields of halodiazirines vary from low to high.

60

Functions Containing Halogens and Any Other Elements

Fluorodiazirines can be prepared directly from amidines (Equation (53)) <1996JA10307> or from the corresponding chloro- or bromodiazirines. The second approach seems to produce better yields of the fluoroderivatives (Scheme 77) <2001JA2628>. N

NH2 NH

12% aq. NaOCl, KF, LiF

N

NaOBr, NaBr, LiBr, 5 °C, 1 h DMSO, hexane, H2O

NH2 p-N3C6H4

NH

N

N

79%

Br N N

p-N3C6H4

40%

Br

N

p-N3C6H4

Bun4NF, MeCN, 25 °C, 4 h

N p-N3C6H4

ð53Þ

F

DMSO, pentane, 30–35 °C

F

Scheme 77

Usually chloro- or bromodiazirines are produced in higher yields than fluorodiazirines obtained by halooxidation of the same starting amidines. Preparation of benzylchloro- and benzylfluorodiazirines from benzylamidine can serve as an example <1997TL7049, 1998JOC3010>. In recent years the formation of chlorodiazirines with a variety of alkyl or arylalkyl substituents has been reported, mainly by Moss et al. Conditions of the reactions are disclosed in the schemes (Schemes 78 and 79) <2001TL8923, 1999TL5101, 1999CC467, 1997TL4379> and in the equations (Equation (54)–(57)) <1996TL279, 1996JA10307, 1999JA5940, 2001OL1439>. NH2 NH

N

HOCl, Graham oxidation

N 40%

Ph

NH2

Ph

NH

Cl

NaOCl

Ph

36%

NH2

NaOCl

NH

35%

Ph

NH

N

Cl N

N

Cl

AcOLi, NaOCl, AcONa, H2O NH2

N

N N Cl

pentane DMSO, 30–35 °C 40%

Scheme 78 H2N

NH

Cl

N N

NaOCl, Li, MeOH 75%

NH2 NH

N

Cl2, NaOH, MeOH, 20 °C, 40 min 56%

Scheme 79

Cl

N

61

Functions Containing Halogens and Any Other Elements NH2

N

12% aq. NaOCl, NaCl, LiCl

NH

N Cl

DMSO, pentane, 30–35 °C

N

NH2

12% aq. NaOCl

NH

NH2

12% aq. NaOCl NH2

NaOCl, H2O

NH

ð55Þ

N

ð56Þ

N

DMSO, pentane, 0 °C

NH

N Cl

DMSO, pentane, 0 °C

Me (CD3)2C

ð54Þ

Cl Me N (CD3)2C N Cl

ð57Þ

Slightly different procedures allowed Sheridan et al. to prepare 3-cycloalkyl or 3-aryl-3-chlorodiazirines in good yields (Scheme 79) <1999TL17, 1999JCS(P2)2257>. 3-Chloro-3-(p-azidophenyl)diazirine and 3-bromo-3-(20 -chloro-10 ,10 ,20 -trifluoroethyl)diazirine have recently been prepared in moderate yields in dimethylsulfoxide at temperatures ranging from 196 to 5 C (Scheme 80) <2001JA2628, 2002JMC1879>.

NH2 p-N3C6H4

F Cl

F F

NH

NH2 NH

NaOCl, NaCl, LiCl, 5 °C, 1 h DMSO, hexane, H2O

N N

p-N3C6H4

43%

Cl

NaOCl, NaBr, LiBr

F

DMSO, –196 to –40 °C

Cl

F

N

F

Br

N

Scheme 80

(i) Tetracoordinated carbon atoms bearing one halogen and two nitro groups (RCHal(NO2)2) The preparation of this type of compounds was widely reviewed and discussed. They can be synthesized by halogenation of salts of dinitroalkane anions using elemental halogens, perchloryl fluorine, or hydrogen halides. Anions of halogenodinitroalkanes easily undergo further transformations, e.g., addition to aldehydes. It seems that no further advances have occurred in this area since the publication of COFGT <1995COFGT(6)35>.

(ii) Tetracoordinated carbon atoms bearing one halogen, one nitro group, and one other nitrogen function Probably the only example of this class is ethyl azidobromocyanoacetate, already reported in <1995COFGT(6)35>.

6.02.2.1.3

Tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one oxygen function

Stable compounds of this class probably do not exist. They are only formed as intermediates in, e.g., Vilsmeier alkylation. For a discussion of their shift to iminium halide salts see chapter 6.02 and the references cited therein <1995COFGT(6)35>.

62 6.02.2.1.4

Functions Containing Halogens and Any Other Elements Tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one sulfur function

Like compounds described in the previous sub-chapter, also species with tetracoordinated carbon atoms bearing one halogen, one nitrogen, and one sulfur function, are nearly always found in the form of the corresponding iminium halide salts. The exceptions are nitrohalosulfides already reported in <1995COFGT(6)35>. There have not been any further advances in this field.

6.02.2.2 6.02.2.2.1

Halogen and Phosphorus Derivatives Tetracoordinated carbon atoms bearing two halogens and one phosphorus function, and one halogen and two phosphorus functions

The synthetic methods for preparing carbohydrates bearing a C-branched substituent of the type CF2-Y (e.g., n-CnF2n+1) where Y = heteroatom (O, S, P) were reviewed. Examples of the syntheses are given (Scheme 81) <2000CAR119>. O

S

O O O F EtO P Li OEt F

O

i. (OR)3 S ii. Ph

O

Cl

(OR)3

moderate-to-high yield

S F O

F P O EtO OEt

F

i. (RO) 2PH, octane, ∆

F

OPh F

F OR P OR S

O

ii. (ButO)2, 37% (OR)3

(OR)3

Scheme 81

(i) From haloalkenes The general approach to compounds of this class involves the addition of phosphines to halogenoalkenes. The reactions can be performed either under polar or photolytic conditions. Some examples were given in chapter 6.02 <1995COFGT(6)35>. No further advances have occurred in this area since that publication.

(ii) From haloalkanes The syntheses of compounds with tetracoordinated carbon atoms bearing two halogens and one phosphorus function involving reactions of haloalkanes with phosphorus derivatives were widely reviewed in chapter 6.02 <1995COFGT(6)35>. Another approach, consisting of the addition of lithium derivatives of dihalomethylphosphates to carbonyl compounds, was also reviewed previously in the work by Plantier–Royon and Portella already cited here <2000CAR119>. Among others lithiation of dibenzyl P-(difluoromethyl)thiophosphate was mentioned (Equation (58)) <1996TL2229>.

F F

S P OBn OBn

LiN(Pr i)2 Hexane, –78 °C

F Li F

S P OBn OBn

ð58Þ

63

Functions Containing Halogens and Any Other Elements

An interesting and effective reduction of phosphate to the corresponding dichloromethylphosphine using lithium aluminum hydride in the presence of aluminum brought about a paper by Guillemin et al. In this work one can also find a large quantity of data concerning phosphorus compounds (Scheme 82) <2001JOC7864>.

AlCl3, LiAlH4 O Cl O P O Cl

(MeOCH2)2O, –80 to –30 °C

Cl

91%

Cl

PH2

Scheme 82

6.02.2.2.2

Tetracoordinated carbon atoms bearing one halogen, one oxygen function, and one phosphorus function

Compounds of this class were not reviewed in chapter 6.02 <1995COFGT(6)35>. As shown by Cairns et al. they can be formed by halogenation of phosphates containing a secondary (or primary) P-alkyl substituent (Equation (59)) <1999PS385>. EtO EtO

O P OEt OEt

TiCl4

Cl

Et2O

EtO

O P OEt OEt

ð59Þ

Work by Chen et al. have indicated that -alkoxy--fluoroalkylphosphates undergo some transformations in which the -alkoxy--fluoroalkylphosphate group is preserved. Thus, the compounds containing hydroxy groups at the P-alkyl chain can be silylated, sulfonated, or can undergo Mitsunobu reaction (Scheme 83) <1996TL8975, 1998JCS(P1)3979>.

Si

O

O OEt P OEt

O

Dowex(H+), EtOH

F

HO

O OEt P OEt

O

HO

57%

i. DEAD, Ph3P, DMF 39%

F

O OEt P OEt

O F

i

O

O OEt P OEt

O F

NH2 N

i= N N

N H

Scheme 83

6.02.2.3 6.02.2.3.1

Halogen and Arsenic Derivatives Tetracoordinated carbon atoms bearing two halogens and one arsenic function

Two known examples of compounds of this class were already reported in COFGT (1995) <1995COFGT(6)35>. Their syntheses involve addition of organoarsenic derivatives to perfluorinated propene <1995COFGT(6)35>.

64 6.02.3

Functions Containing Halogens and Any Other Elements FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLY A CHALCOGEN AND/OR GROUP 15 ELEMENT

6.02.3.1

Halogen and Silicon Derivatives

A variety of ,-dihaloalkyl silanes were prepared using different routes but only some of them are more general. A few more examples of the most common syntheses disclosing detailed conditions were reported in chapter 6.02 <1995COFGT(6)35>. A few years ago a review was published covering preparation and reactivity of perfluoroalkyl and difluoroalkyl silanes <1997CRV757>. Two following references cited there appertain to difluorosilanes <1995SL717, 1997JA1572>. 6.02.3.1.1

Dichlorocarbene addition

Dichlorocarbene generated from phenyl(bromodichloromethyl)mercury adds to a variety of silanes, giving the corresponding dichloromethyl silanes <1995COFGT(6)35>. 6.02.3.1.2

Other additions to silanes

Addition of bromine to alkynyl silanes results in an almost quantitative formation of tetrabromoalkyl silanes. Also addition of methylmagnesium bromide to trichlorosilyldichloromethane leads to the formation of trimethylsilyldichloromethane. Photochemical addition of the chlorosilylradical to tetrafluoroethene affords a very high yield of the corresponding adduct. Some of the reported examples concern syntheses of systems containing silicon, halogen, and chalcogen (oxygen or sulfur) at the same carbon atom. Such syntheses can be accomplished, for example, starting from (methylthiomethyl)trimethyl silane <1995COFGT(6)35>. 6.02.3.1.3

Substitution of silanes by haloalkyl derivatives

Electrochemical silylation of chlorodifluoromethyl enol ethers affords the new functionalized difluoromethyl allyl silanes on a preparative scale in good yields. These silanes react as difluoromethyl anion equivalents with electrophiles, e.g., aldehydes (Scheme 84) <1998TL3137>.

Cl CF2

4Me3SiCl, Bu4NBr DMF, Mg/Ni electrodes

EtO R

Si CF2 EtO R

R = Ph, 94% R = -(CH2)2Ph, 66%

Scheme 84

Petrov published a simple procedure for nucleophilic perfluoroalkylation of organic and inorganic substrates. A mixture of iodoperfluoroalkane and tetrakis(dimethylamino)ethylene is used for the nucleophilic perfluoroalkylation. The reaction of chlorotrimethyl silane and iodoperfluoroalkane/ tetrakis(dimethylamino)ethylene in diglyme results in the formation of perfluoroalkyltrimethyl silanes isolated in 55–81% yield. The interaction of this system with organic electrophiles, such as benzoyl and benzensulfonyl chlorides, aliphatic and aromatic aldehydes, or activated ketones, leads to the formation of the corresponding condensation products in 24–62% yield (Scheme 85) <2001TL3267>. (Me2N)2C=C(NMe2)2, ClSiMe3 RfI

Diglyme, –30 °C, 2 h, 55–81% Rf = C2F5, n-C3F7, n-C4F9

Scheme 85

RfSiMe3

Functions Containing Halogens and Any Other Elements 6.02.4

65

Halogen and Boron Derivatives

A review has recently appeared on perfluoroalkylborates as congeners of perfluoroalkanes <2001CCR243>. Apart from that review no interesting reports have been found in this area since the publication of chapter 6.02 <1995COFGT(6)35>. Compounds of this class are usually extremely unstable and probably due to this instability they have not found wider applications in organic synthesis.

6.02.5

Halogen and Germanium Derivatives

Jones and Matthews in chapter 6.02 <1995COFGT(6)35> reported several examples of efficient syntheses of compounds of this class. It seems that since then no advances in this area have been reported. The compounds can preferably be prepared either by addition of germane halogenides to chlorinated alkenes or by treating bis(perhaloalkyl)mercury compounds with germane halogenides. It is worth mentioning that trihalo(perfluoroalkyl)germanium derivatives are versatile synthetic intermediates in formation of alkyl(perfluoroalkyl)germanium products.

6.02.6

6.02.6.1

FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP 15 ELEMENT, A CHALCOGEN OR A METALLOID Halogen and Lithium Derivatives

Haloalkyllithium compounds, due to their unusual reactivity and their ability to deliver halomethylene group to required acceptors, are commonly used in several syntheses. Very critical aspects of their use concern solvents and reaction temperatures. Metallation of terminal iodofluoroalkanes with methyllithium at 78 C in THF, followed by the addition of sulfur dioxide, results in the formation of a lithium difluoroalkylsulfinate via intermediate organolithium species chapter 6.02 <1995COFGT(6)35>. Rosnati, reviewing results achieved in fluoroorganic chemistry up to 1995, <1996T1> pointed to the addition of perfluoroalkyllithium to imines reported earlier by Uno et al. <1988CL729> and <1992JOC1504>. C-Lithiation of difluoromethyl group attached to phosphorus was reported by Piettre and Raboisson (Equation (60)) <1996TL2229>. F F

6.02.6.2

S P OBn OBn

LiN(Pri)2 Hexane, –78 °C

F Li F

S P OBn OBn

ð60Þ

Halogen and Magnesium Derivatives

Transmetallation reaction between Grignard reagents and perhalogenated systems is a versatile route to compounds of this class; e.g., arylmagnesium bromides react with 1-iodoperfluoroalkanes at low temperatures to produce perfluoroalkylmagnesium bromides, which can be used further without separation chapter 6.02 <1995COFGT(6)35>. Applications of perfluoroalkyl Grignard reagents (CnH2n+1MgX) in the synthesis of some fluorinated amines and diamines were reported by Katritzky et al. <1997TL7015>. Perfluoro-n-octylmagnesium bromide can be prepared with 1-bromo-1H-heptadecafluorooctane and hexylmagnesium bromide in THF at 60 C in 30 min <2001JOC1316>. The reaction of heptafluoropropylmagnesium bromide with sym-ketodibenzo-16-crown-5 at 78 to 20 C in Et2O produced the corresponding alcohol in 60% yield <2000JHC1337>. Perfluoroalkenyl ketones were obtained by reaction of perfluorometallic reagents with acyl silanes. Long-chain F-alkylations of sugar derivatives were carried out with F-organomagnesium bromides prepared in situ from F-alkyl iodides and ethylmagnesium bromide according to the method reported by Burton and Yang <1998T189>, or with F-alkyltrimethyl silane <1989PGE380554> in order to compare the influence of the method on the stereoselectivity. Examples are shown in the Scheme 86 <2002TL1677>.

66

Functions Containing Halogens and Any Other Elements EtMgBr, ether C4F9I

C4F9MgBr in situ

–45 °C, 0.5 h

Sugar

C4F9-sugar derivative

O CnF2n + 1CF2CF2Li or CnF2n + 1CF2CF2MgBr

O

RCSiMe3 lt – rt, 77–86%

F

R

CnF2n + 1 F

Scheme 86

DesMarteau and Creager presented, at the 226th National Meetings of the American Chemical Society, the paper describing applications of oligomeric bis[(perfluoroalkyl)sulfonyl]imide lithium salts as electrolytes for rechargeable lithium batteries <2003MI36>.

6.02.6.3

Halogen and Copper Derivatives

The reaction of copper metal with 1-iodoperfluoroalkanes at an elevated temperature is known to produce perfluoroalkylcopper(I). No further advances have occurred in this area since the publication of chapter 6.02 <1995COFGT(6)35>.

6.02.6.4

Halogen and Silver Derivatives

An equilibrium between the mixtures of di(perfluoroalkyl)cadmium(II) with silver nitrate and forming di(perfluoroalkyl)silver(I) anion was studied in dimethyl formamide and triethylamine at a low temperature (Equation (61)) <1997JOM79>. Equilibrium

Cd(CnF2n + 1)2 + AgNO3

DMF or Et3N, –30 °C

[Ag(CnF2n +1)2] –

ð61Þ

CnF2 n +1 = CF3, CF3CF2, CF3CF2CF2, (F3C)2CF

The formation of organometallic compounds, bearing ,-dihaloalkyl groups, in reactions of silver trifluoroacetate with perhalogenated ethene, promoted by caesium fluoride, was reported earlier. No further advances have occurred in this area since the publication of chapter 6.02 <1995COFGT(6)35>.

6.02.6.5

Halogen and Zinc Derivatives

A review on Reformatsky syntheses was published a few years ago <1999JOM215>. In this review the use of perfluoroalkylzinc by Kitazume and Ishikawa was mentioned <1985JA5186>. No further reports have been found in this area since the publication of chapter 6.02 <1995COFGT(6)35>.

6.02.6.6

Halogen and Cadmium Derivatives

Cadmium metal inserts rather easily between carbon and halogen atoms in haloalkanes to yield organocadmium reagents <1995COFGT(6)35>. The synthetic methods for preparing compounds bearing substituent such as CF2-Y were reviewed. Among others an example of the synthesis via cadmium intermediate was reported (Scheme 87) <2000CAR119>. Bis(perfluoroalkyl)cadmium reacts reversibly in organic solvents like dimethyl formamide or triethylamine at a low temperature with silver nitrate to yield bis(perfluoroalkyl)silver anion. An

Functions Containing Halogens and Any Other Elements

67

equilibrium of the reaction was studied (Equation (61)) <1997JOM79>. No further advances have occurred in this area since the publication of chapter 6.02 <1995COFGT(6)35>.

O F (EtO)2P Br F

Cd THF

O F (EtO)2P CdBr F

Br, rt

O F (EtO)2P F

62%

Scheme 87

6.02.6.7

Halogen and Mercury Derivatives

Mercuric fluoride adds readily to perhaloalkenes at elevated temperatures. Perhalodialkylmercury compounds are formed in the reaction. There have not been any further advances in this field since the publication of chapter 6.02 <1995COFGT(6)35>.

6.02.6.8

Halogen and Tin Derivatives

A few typical approaches to ,-dihaloalkyltin derivatives were reported earlier. They involve, for example, insertion of tin(II) chloride or fluoride into iodoperfluoroalkanes, the addition of dialkyltin hydrides to perfluorinated alkenes or transmetallation reactions <1995COFGT(6)65> Now some more recent examples of syntheses of ,-dihaloalkyltin derivatives are presented. The reaction of perfluoropropylmagnesium chloride (obtained from perfluoropropyl iodide and propylmagnesium chloride), with tin(IV) chloride was reported to give tetra(perfluoropropyl)stannane. In a similar manner perfluoropropylmagnesium chloride reacts with other tin(IV) derivatives. Yields of products are from poor to very good depending on the starting tin species (Scheme 88) <1995JOM131>.

PrMgCl, Et2O

C3F7I

–70 °C

C3F7MgCl

C3F7MgCl

SnCl4, Et2O, –70 to –30 °C

(C3F7)4Sn

19%

C3F7MgCl

MeSnCl3 11% MeSnCl3

C3F7MgCl

C3F7MgCl

49% H2C=CH-SnCl3 96% Me2SnBr2

C3F7MgCl

C3F7MgCl

82% (H2C=CH)2SnBr2 46%

Scheme 88

MeSn(C3F7)3

MeSn(C3F7)2Cl

H2C=CH-Sn(C3F7)2Cl

(C3F7)2Me2Sn

(H2C=CH)2Sn(C3F7)2

68 6.02.6.9

Functions Containing Halogens and Any Other Elements Halogen and Lead Derivatives

It was reported earlier that perfluoroalkyl iodides reacting with tetramethyllead at an elevated temperature afford perfluoroalkyltrimethyllead in low yields. No further advances have occurred in this area since the publication of chapter 6.02 <1995COFGT(6)35>.

6.02.6.10

Halogen and Ruthenium Derivatives

Compounds described here have not been reported in COFGT (1995) <1995COFGT(6)35>. In conjunction with two other independent minor reviews of organometallic main group fluorides <1997MI351> and f-block fluorides <1997JFC(86)121>, an extensive review appeared in 1997 on compounds containing carbonmetalfluorine fragments of d-block metals <1997CRV3425>. For the purpose of the reviews the term ‘‘organometallic fluoride’’ was used strictly to describe compounds containing fluorinemetal and carbonmetal bonds with the same metal atom. Nevertheless, at least a few examples included in the latter review refer to preparation of compounds, which contain such structural fragment as MCF2H where M is Ru <1997JA3185, 1994IC1476>. Me3SiCF3 reacts smoothly with RuHF(CO)(P(Bu-t)2Me) forming Me3SiF and a six-coordinated product where -F migration occurred in the proposed reaction intermediate. A fluoride atom abstraction using Me3SiOTf leads to an unusual rearrangement, in which coordinated hydride migrates to the carbene, forming CF2H fragment (Scheme 89). Experimental evidences suggest that this rearrangement occurs by a mechanism involving dissociation of one phosphine ligand. The CF2 group is readily converted to CO by the addition of water.

H L OC Ru F L

H L OC Ru F L

Me3SiOTf –Me 3SiF

Me3SiCF3 –Me 3SiF

L OC Ru F L F F

H L OC Ru F L F F

L OC Ru F L F F

THF

Scheme 89

6.02.6.11

Halogen and Cobalt or Nickel Derivatives

Compounds described here were not reported in <1995COFGT(6)35>. Perfluorometallacyclic compound Ni(PEt3)2(CF2)4 reacts irreversibly with BF3OEt2 complex affording unprecedented perfluorometallacycle with a phosphonium ylide structure. A reaction with sequence involving extraction of fluoride ions from the coordinated perfluorometallacycle followed by quenching the carbene species by migration of a phosphine ligand from the metal to carbon is likely (Equation (62)) <1988OM1642> acc. to <1997CRV3425>. +

F F F Et3P Ni Et3P F

F

F F F

BF3–OEt2

–

F

F4B Ni Et3P F

PEt3 F F

F

ð62Þ

F F

Fluoroalkylphosphine complexes of nickel(0) and cobalt(I) were also described. Treatment of (cod)2Ni with dfepe [(dfepe = (C2F5)2PCH2CH2P(C2F5)2, cod = 1,5-cyclooctadiene)] yields (dfepe)Ni(cod) and then (dfepe)Ni(bipy) (Scheme 90) <2003JOM65>.

Functions Containing Halogens and Any Other Elements

(acac)2Ni

(cod)2Ni

(CO)8Co

But3Al, butadiene

69

(dfspe)2Ni

dfepe excess, 82% dfepe

(dfepe)Ni(cod)

Toluene, 25 °C, 24 h, 80% LiEt3BH, THF (CO)4Co

i. dfepe, ii. HBF4, Me2O

(dfspe)(CO)2Co(H) stable up to –30 °C

Scheme 90

6.02.6.12

Halogen and Palladium or Platinum Derivatives

The first edition of COFGT (1995) <1995COFGT(6)35> reported neither examples of palladium nor platinum derivatives. The annual survey on transition metals in organic synthesis (covering 1993) brought, among others, an example of the reaction in which, in an intermediate, the PdCF2 bond is possibly formed (Equation (63)) <1995CCR153>. RCOCF2I

R' , L4Pd

RCOCF2 R

ð63Þ

I

Very recently it has been announced that the reaction of (1,5-cyclooctadiene = cod) (cod)PtMe2 with one molar equivalent of C4F9I in hexane, produces the stable perfluoroalkylplatinum (cod)PtMeC4F9 complex (Equation (64)) <2002POL2357>. C4F9I, N2, 12 h Pt

53%

Pt

C4F9

ð64Þ

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Rao, Tetrahedron 2000, 56, 3539–3546. M. F. Greaney, W. B. Motherwell, Tetrahedron Lett. 2000, 41, 4463–4466. Y. Kuroki, D. Asada, Y. Sakamaki, K. Iseki, Tetrahedron Lett. 2000, 41, 4603–4608. M. Mae, H. Amii, K. Uneyama, Tetrahedron Lett. 2000, 41, 7893–7896. G. Pawelke, H. Burger, Coord. Chem. Rev. 2001, 215, 243–266. N. Yoneda, T. Fukuhara, Chem. Lett. 2001, 3, 222–223. H. Eto, Y. Kaneko, S. Takeda, M. Tokizawa, S. Sato, K. Yoshida, S. Namiki, M. Ogawa, K. Maebashi, K. Ishida, M. Matsumoto, T. Asaoka, Chem. Pharm. Bull. 2001, 49, 173–182. A. Nicolaides, T. Enoyo, D. Miura, H. Tomioka, J. Am. Chem. Soc. 2001, 123, 2628–2636. Y. Guo, Q. Y. Chen, J. Fluorine Chem. 2001, 107, 89–96. N. Roques, J. Fluorine Chem. 2001, 107, 311–314. T. Abe, H. Baba, I. Soloshonok, J. Fluorine Chem. 2001, 108, 21–36. L. E. Kiss, I. Koevesdi, J. Rabai, J. Fluorine Chem. 2001, 108, 95–110. K. I. Petko, L. M. Yagupolskii, J. Fluorine Chem. 2001, 108, 211–214. T. Abe, H. Baba, I. Soloshonok, J. Fluorine Chem. 2001, 108, 215–228. V. A. Petrov, S. Swearingen, W. Hong, W. C. Petersen, J. Fluorine Chem. 2001, 109, 25–32. C. R. Burkholder, W. R. Dolbier, M. Medebielle, J. Fluorine Chem. 2001, 109, 39–48. L. V. Kudzma, Ch. G. Huang, R. A. Lessor, L. A. Rozov, S. Afrin, F. Kallashi, C. McCutcheon, K. Ramig, J. Fluorine Chem. 2001, 111, 11–16. S. Rozen, D. Rechavi, A. Hagooly, J. Fluorine Chem. 2001, 111, 161–165. T. Okazoe, K. Watanabe, M. Itoh, D. Shirakawa, S. Tatematsu, J. Fluorine Chem. 2001, 112, 109–116. V. Petrov, J. Fluorine Chem. 2001, 112, 117–121. A. Sekiya, H. Quan, M. Tamura, R. X. Gao, J. Murata, J. Fluorine Chem. 2001, 112, 145–148. V. A. Petrov, J. Fluorine Chem. 2001, 112, 325–328. G. Li, A. Graham, W. Potter, Z. D. Grossman, A. Oseroff, T. J. Dougherty, R. K. Pandey, J. Org. Chem. 2001, 66, 1316–1325. J. C. Guillemin, T. Janati, J. M. Denis, J. Org. Chem. 2001, 66, 7864–7868. Y. Gao, J. Voigt, H. Zhao, G. C. G. Pais, X. Zhang, L. Wu, Z. Y. Zhang, T. R. Burke, J. Med. Chem. 2001, 44, 2869–2878. B. A. Ameduri, B. Boutevin, G. Kostov, Progress in Polym. Sci. 2001, 26, 105–187. R. A. Moss, F. Zheng, K. Krogh-Jespersen, Org. Lett. 2001, 3, 1439–1442. E. Magnier, E. Vit, C. Wakselman, Syn. Lett. 2001, 8, 1260–1262. H. D. Quan, M. Tamura, R. Gao, A. Sekiya, Tetrahedron 2001, 57, 4111–4114.

Functions Containing Halogens and Any Other Elements 2001TL3009 2001TL3267 2001TL4861 2001TL8923 2002BCJ(75)1597 2002CEJ2917 2002IZV(6)948 2002JFC(113)79 2002JFC(113)97 2002JFC(113)201 2002JFC(114)51 2002JFC(115)21 2002JFC(116)109 2002JFC(117)149 2002JFC(118)123 2002JMC1879 2002JPCA3114 2002POL2357 2002SL996 2002T4077 2002T5877 2002TL1677 2002TL2949 2002TL7353 2003JOM65 2003MI(8)282 2003MI(8)307 2003MI36 2003TL5061 2003TL5995 2003USP073588

73

S. M. Riyadh, H. Ishii, T. Fuchigami, Tetrahedron Lett. 2001, 42, 3009–3012. V. A. Petrov, Tetrahedron Lett. 2001, 42, 3267–3269. K. Suzuki, H. Ishii, T. Fuchigami, Tetrahedron Lett. 2001, 42, 4861–4864. R. A. Moss, W. Ma, S. Yan, F. Zheng, Tetrahedron Lett. 2001, 42, 8923–8926. S. Ayuba, N. Yoneda, T. Fukuhara, S. Hara, Bull. Chem. Soc. Jpn. 2002, 75, 1597–1604. G. Blond, T. Billard, B. R. Langlois, Chem. Europ. J. 2002, 8, 2917–2922. A. N. Kovregin, A. Yu. Sizov, A. F. Ermolov, Izv. Akad. Nauk. Ser. Khim. 2002, 6, 948–950. (Chem. Abstr. 2003, 138, 136683). K. Wu, Q. Y. Chen, J. Fluorine Chem. 2002, 113, 79–83. J. Murata, M. Tamura, A. Sekiya, J. Fluorine Chem. 2002, 113, 97–100. N. V. Ignat’ev, M. Schmidt, U. Heider, A. Kucherina, P. Sartori, F. M. Helmy, J. Fluorine Chem. 2002, 113, 201–206. O. Paleta, J. Palecek, J. Michalek, J. Fluorine Chem. 2002, 114, 51–54. D. Velayutham, K. Jayaraman, M. Noel, S. Krishnamoorthy, P. Sartori, J. Fluorine Chem. 2002, 115, 21–26. C. H. Deng, C. J. Guan, M. H. Shen, C. X. Zhao, J. Fluorine Chem. 2002, 116, 109–116. I. Dlouha, J. Kvicala, O. Paleta, J. Fluorine Chem. 2002, 117, 149–160. Y. Cheburkov, G. J. Lillquist, J. Fluorine Chem. 2002, 118, 123–126. R. G. Eckenhoff, F. J. Knoll, E. P. Greenblatt, W. P. Dailey, J. Med. Chem. 2002, 45, 1879–1886. C. Clower, K. M. Solntsev, J. Kowalik, L. M. Tolbert, D. Huppert, J. Phys. Chem. A 2002, 106, 3114–3122. R. P. Hughes, J. S. Overby, K. C. Lam, C. D. Incarvito, A. R. Rheingold, Polyhedron 2002, 21, 2357–2360. S. Gouault, J. C. Pommelet, T. Lequeux, Syn. Lett. 2002, 6, 996–998. K. Wu, Q. Y. Chen, Tetrahedron 2002, 58, 4077–4084. S. M. Riyadh, H. Ishii, T. Fuchigami, Tetrahedron 2002, 58, 5877–5884. F. Chauteau, M. Essers, R. Plantier-Royon, G. Haufe, C. Portella, Tetrahedron Lett. 2002, 43, 1677–1680. A. V. Matsnev, N. V. Kondratenko, Yu. L. Yagupolskii, L. M. Yagupolskii, Tetrahedron Lett. 2002, 43, 2949–2952. A. Kamal, T. B. Pratap, K. V. Ramana, A. V. Ramana, A. H. Babu, Tetrahedron Lett. 2002, 43, 7353–7356. B. L. Bennett, S. White, B. Hodges, D. Rodgers, A. Lau, D. M. Roddick, J. Organomet. Chem. 2003, 679, 65–73. A. M. Caminade, C. O. Turrin, P. Sutra, J. P. Majoral, Current Opinion in Colloid and Interface Science 2003, 8, 282–295. T. Imae, Current Opinion in Colloid and Interface Science 2003, 8, 307–314. DesMarteau, D. D.; Creager, S. E. 2003, 226th National Meetings of the American Chemical Society, paper No. FLUO 36. S. Gouault, C. Guerin, L. Lemoux, T. Lequeux, J. C. Pommelet, Tetrahedron Lett. 2003, 44, 5061–5064. D. V. Sevenard, P. Kirsch, E. Lork, G. V. Roschenthaler, Tetrahedron Lett. 2003, 44, 5995–5998. J. L. Howell, E. W. Perez, US Patent 073588 (2003) (Chem. Abstr. 2003, 138, 323717).

74

Functions Containing Halogens and Any Other Elements Biographical sketch

Dr. Jerzy Suwin´ski, Prof. of Organic Chemistry, was born in 1939, graduated in 1961, obtained his Ph.D. in organic chemistry under Prof. C. Troszkiewicz’s supervision at Silesian University of Technology (Gliwice, Poland) in 1968. A few years later 1973/1974 he joined Prof. A. R. Katritzky’s research group as a postdoc. Back in Gliwice he received his D.Sc. degree in 1978 and later on in 1990 a position of Full Professor of Organic Chemistry. As a contract professor he lectured in Bologna, Italy (1986, 1991), Missouri Univ., USA (1994), Campinas, Brazil (1995), Poznan´, Poland (1997) and as visiting professor also in other countries. His main research interest is concerned with reaction mechanisms and nitrogen heterocycles. He is author or co-author of over 130 papers, books, and textbooks for students.

Dr. Krzysztof Walczak, Associate Professor of Organic Chemistry, was born in 1955, graduated in 1980, and obtained his Ph.D. degree in Organic Chemistry at the Silesian University of Technology (Gliwice, Poland) in 1988 under Professor J. Suwin´ski’s supervision. He continued his scientific education as a post-doctoral fellow (1989–1991) at the Odense University (Denmark) with Professor E. B. Pedersen. In 1996 he was granted a sixmonth fellowship founded by the Rectors Conference of Danish Universities and joined again Professor’s Pedersen research group at Odense University. In 1999 he received D.Sc. degree. Since then he remains at STU with exception of two sabbaticals: at the Utah State University in Logan (USA) with Professor Lance Seefeldt and in Nucleic Acids Centre of University of Southern Denmark as a contract professor. His current research activity is focused on the chemistry of heteroarenes including their sugar derivatives. He has published around 35 papers.

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 23–74

6.03 Functions Containing Three Chalcogens (and No Halogens) S. RA´DL Research Institute of Pharmacy and Biochemistry, Prague, Czech Republic and S. VOLTROVA´ Institute of Chemical Technology, Prague, Czech Republic 6.03.1 INTRODUCTION 6.03.2 FUNCTIONS BEARING THREE OXYGEN ATOMS 6.03.2.1 Methods for the Preparation of Carboxylic Ortho-esters and Related Compounds 6.03.2.1.1 Ortho-esters from 1,1,1-trihaloalkanes, ,-dihaloethers and -haloacetals 6.03.2.1.2 Ortho-esters from imidate ester salts 6.03.2.1.3 Ortho-esters from carboxylic acids and derivatives 6.03.2.1.4 Ortho-esters from dioxacarbenium salts 6.03.2.1.5 Ortho-esters from 1,1-dialkoxyalkenes 6.03.2.1.6 Ortho-esters from 1,1-dialkoxycyclopropanes and related compounds 6.03.2.1.7 Ortho-esters from acetals 6.03.2.1.8 Ortho-esters from ortho-carbonate esters and trialkoxyacetonitriles 6.03.2.2 Preparation of Carboxylic Ortho-esters from Other Ortho-esters 6.03.2.2.1 Trans-esterification reactions 6.03.2.2.2 Modification of R1 and R2 of R1C (OR2)3 6.03.3 FUNCTIONS BEARING THREE SULFUR ATOMS 6.03.3.1 Methods for the Preparation of Trithio-ortho-esters and Related Compounds 6.03.3.1.1 Trithio-ortho-esters from RC(X1)(X2)X3 6.03.3.1.2 Trithio-ortho-esters from thioimidate esters salts 6.03.3.1.3 Trithio-ortho-esters from carboxylic acids and derivatives 6.03.3.1.4 Trithio-ortho-esters from dithia- and trithiacarbenium salts 6.03.3.1.5 Trithio-ortho-esters from dithioacetals 6.03.3.1.6 Trithio-ortho-formates from trithiocarbonates 6.03.3.1.7 Trithio-ortho-formates from tetrathio-ortho-carbonates 6.03.3.1.8 Miscellaneous 6.03.3.2 Preparation of Trithio-ortho-esters from Other Trithio-ortho-esters 6.03.3.2.1 Higher trithio-ortho-esters from trithio-ortho-formate esters 6.03.3.2.2 Trans-esterification of trithio-ortho-esters 6.03.3.3 Methods for the Preparation of Oxidized Derivatives of Trithio-ortho-esters 6.03.3.3.1 Oxidized trithio-ortho-esters containing at least one sulfoxide group 6.03.3.3.2 Oxidized trithio-ortho-esters containing at least one sulfone group 6.03.3.3.3 Oxidized trithio-ortho-esters containing at least one sulfonate group 6.03.4 FUNCTIONS BEARING THREE SELENIUM ATOMS 6.03.4.1 Methods for the Preparation of Triseleno-ortho-esters 6.03.4.1.1 Triseleno-ortho-esters from triselenacarbenium salts 6.03.4.1.2 Triseleno-ortho-esters from diselenoacetals and related compounds

75

75 76 76 76 77 77 80 81 81 81 81 82 82 83 84 84 84 85 85 85 85 86 88 88 89 89 93 94 94 95 97 98 98 98 98

76

Functions Containing Three Chalcogens (and No Halogens)

6.03.5 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN 6.03.5.1 Methods for the Preparation of Functions R1C(OR2) (OR3)SR4 6.03.5.1.1 From R1C(X1)(X2)X3 6.03.5.1.2 Miscellaneous 6.03.5.2 Methods for the Preparation of Functions R1C(OR2) (SR3)SR4 6.03.5.2.1 From R1C(X1)(X2)X3 6.03.5.2.2 From dithiacarbenium salts 6.03.5.2.3 From dithioacetals and related compounds 6.03.5.2.4 From ketene dithioacetals 6.03.5.2.5 Miscellaneous 6.03.5.3 Methods for the Preparation of Functions R1C (OR2) (OR3)SeR4 6.03.6 MIXED SULFUR AND SELENIUM FUNCTIONS 6.03.6.1 Methods for the Preparation of Functions R1C(SR2) (SR3)SeR4 6.03.6.1.1 From dithioacetals 6.03.6.2 Methods for the Preparation of Functions R1C(SR2) (SeR3)SeR4 6.03.7 MIXED OXYGEN, SULFUR, AND SELENIUM FUNCTIONS

6.03.1

98 98 98 100 100 100 101 101 101 105 105 105 105 105 106 106

INTRODUCTION

As in COFGT (1995) <1995COFGT(6)67>, this chapter covers synthesis of compounds of general formula RC(X)(Y)Z where each of X, Y, and Z are independently linked through O, S, Se, and Te atoms. No compound of this type containing Te atoms has been reported in the literature, so only compounds containing O, S, and Se are discussed. In some cases older principal articles omitted in the basic work are included. Since 1993, no general review focused on preparation of the structural types covered by this chapter has appeared.

6.03.2

FUNCTIONS BEARING THREE OXYGEN ATOMS

6.03.2.1 6.03.2.1.1

Methods for the Preparation of Carboxylic Ortho-esters and Related Compounds Ortho-esters from 1,1,1-trihaloalkanes, a,a-dihaloethers and a-haloacetals

The extended Williamson synthesis of ortho-esters by nucleophilic displacement of three halogen atoms in 1,1,1-trihaloalkanes by sodium alkoxides has been used rarely owing to low yields <1995COFGT(6)67>. However, 3-chloro-2-trimethoxymethyl- or triethoxymethylpyrrole derivatives (2, R = Me, Et) have been prepared <1999T4133> from 3,3-dichloro-2-trichloromethyl-1-pyrroline 1 and 10 equiv. of the corresponding sodium alkoxide in 97% and 79% yields, respectively (Equation (1)). Cl N

Cl

Cl Cl

79–97% R = Me, Et

Cl

OR OR OR

H N

NaOR

ð1Þ

Cl 2

1

Nucleophilic displacement of the halogen atoms of ,-dihaloethers (e.g., 2,2-dichloro2-methoxyacetate <1995TL1827>) also gives ortho-esters. Thus, L-dimethyl tartrate was treated with phenylmagnesium bromide to give optically active tetraol 3, which reacted with the above mentioned dihaloether to afford the ortho-ester 4 used as a chiral auxiliary in the synthesis of -hydroxy acids (Equation (2)).

HO Ph

Ph

OH

OH 3

Ph + OH Ph

MeO

Cl Cl CO2Me

Py 90%

HO Ph

Ph O

O O MeO2C 4

Ph Ph

ð2Þ

77

Functions Containing Three Chalcogens (and No Halogens)

Reaction of bromomalonaldehyde tetraethylacetal 5 <1995T8623> with potassium t-butoxide afforded triethyl 3,3-diethoxy-ortho-propionate 6 via elimination of hydrogen bromide to diethoxymethylketene diethylacetal (Scheme 1), cf. Section 6.03.2.1.5 OEt OEt

OEt OEt

t-BuOK EtO

OEt

EtO

Br 5

EtOH

OEt

OEt OEt OEt EtO OEt 6

Scheme 1

6.03.2.1.2

Ortho-esters from imidate ester salts

Owing to the limited use of the Pinner method <1995T8623>, iminium salts were prepared from secondary or tertiary amides 7 <1997TL8499> by reaction with trifluoromethanesulfonic anhydride in the presence of pyridine at low temperatures. The resulting imino and iminium triflates afforded ortho-esters 8 by reaction with alcohols (Scheme 2, R1 = e.g., Ph(CH2)2, R2 and R3 = H or alkyl, R4 = alkyl). The yields of bridged ortho-ester 9 formed by reaction of suitable amides with 2,2-bis(hydroxymethyl)-propan-1-ol were 59–88%. O R1

N R3 7

R2 Tf2O, Py

OTf OR4 4 2 R4OH + R + R2 R OH R1 N R1 N R3 R3

OR4 4 OR R1 OR4 8

Scheme 2

O O O Ph 9

Sugar 1,2-cyclic ortho-esters 12 can be prepared <2000CAR(329)879> from the corresponding peracetylated trichloroacetimidate 10 and t-butyldimethylsilylated alcohol 11 under the action of usual promoters for trichloroacetimidate donors (0.1 equiv.): TMDMSOTf, BF3Et2O, TfOH, AgOTf, in dry dichloromethane using 4 A˚ molecular sieves (Scheme 3).

AcO AcO

O Ph O TBDMSO

OAc O +

AcO O

CCl3

O Ph O TBDMSO

O HO O

O

89%

NH 10

O

AcO AcO

11

O O

OO

AcO 12

Scheme 3

6.03.2.1.3

Ortho-esters from carboxylic acids and derivatives

Bicyclic ortho-esters reviewed in COFGT (1995) <1995COFGT(6)67> have been repeatedly used as suitable protecting groups for polyfunctionalized carboxylic acids. A new method of utilizing ortho-esters 15 both for protection and asymmetric synthesis has been developed <1997PAC639,

78

Functions Containing Three Chalcogens (and No Halogens)

1997T16575, 2003CC776>. The compounds can be prepared from oxiranes 13 using zirconocene and AgClO4 in CH2Cl2 at mild conditions (room temperature, 15 min). Mechanistically, this ortho-ester formation proceeds via dioxacarbenium ion intermediate 14 (Scheme 4).

R

O

O

Cp2(Cl)Zr-Cl

R

AgClO4

O

Zr+(Cl)Cp2 O O O

13

O

R

O

O

O

C(2)-attack

+ R O Zr(Cl)Cp2O

–Cp2(Cl)Zr+

15

14

Scheme 4

Ortho-pivalates, as sugar protecting groups were prepared by reaction of pivaloyl chloride and free sugar using an HF-supported procedure <1994LA965, 1999JPR41> or by intramolecular orthoesterification using dicyclohexylcarbodiimide (DCC) <1996MM6126, 2002CAR(337)951> or thiourea in pyridine <1998CAR(308)439>. The last procedure is exemplified in Scheme 5 by preparation of 18 from 16. During these procedures, dioxacarbenium ion intermediates, e.g., 17, are formed.

H

O OR

RO

Cl

NH2CSNH2

RO O MCA

80 °C, 6 h

OR

H RO

O MCA

16

RO

O

O

H

O+O

66 %

O O

O OR

17

18

MCA = ClCH2CO R = Me3CCO

Scheme 5

Similar conversion of a series of peracetylated sugars into the corresponding 1,2-ortho-esters via in situ generation of glycosyl iodides promoted by I2/Et3SiH followed by addition of the respective alcohol has also been reported <2003TL7863>. Formation of oleanolyl 1,2-O-ortho-acetates instead of expected glycosides was studied under the conditions of Ko¨nigs–Knorr glycosidation <2001M839>. Thus, acetobromo sugars with diphenylmethyl-oleanolate in the presence of drierite, Ag2O, and iodine in dry chloroform afforded ortho-esters 19, where R = OAc, peracetylated - or -D-glucopyranosyl, or -D-galactopyranosyl, in ca. 30% yields.

OAc

H O

O OAc R

O O O

H

O

Ph Ph

H 19

Oxidative cyclization–methoxycarbonylation of propargylic acetates 20 in the presence of (CH3CN)2PdCl2/p-benzoquinone <2002TL6587> in methanol at 0 C under CO atmosphere afforded (E)-cyclic ortho-esters 21 in moderate yields (Equation (3), R1 = Me, R2 = Bn, or R1R2 = (CH2CH2)2N-BOC).

Functions Containing Three Chalcogens (and No Halogens) R1

R 1 R2 AcO

i

O

79

R2 O

O O

ð3Þ

O 21

20

i. (MeCN)2PdCl2/p-benzoquinone, MeOH, CO, 0 °C

The mechanism proposed for this reaction includes formation of a vinyl palladium intermediate, which is subjected to nucleophilic attack of MeOH on the carbon atom of the acetyl group followed by CO insertion and methanolysis to provide the ortho-ester product 21 (Scheme 6).

R1 R 2 AcO 20

Hydroquinone Benzoquinone R1 R2 O

MeO

Pd2+

R1 R2 Pd2+ O

Pd(0)

O

CO2Me

O 21

MeOH O

R1 O

R1 2 R O + Pd+ O

R2

O H

COPd+ MeOH

H

CO

Scheme 6

Bis(trifluoroacetates) 22 react with bis(epoxides) 23 under the conditions of cycloaddition polymerization to form poly(cyclic ortho-esters) 24 (Equation (4), R1 =(CH2)4, CH2C6H4CH2, R2 =(CH2)2, C6H4C(CH3)2C6H4). The yields are generally between 75% and 96% depending on the catalysts (onium salts, e.g., TBABr, TBACl, TBAI, tetrabutylphosphonium bromide) or solvents (N-methyl-2-pyrrolidone (NMP), anisole, chlorobenzene, tetrahydrofuran (THF), sulfolane) used <1995MM3490>. O F3C

O O

R1

+

O

CF3

R2

O

O

O

O

23

22

O O

O

1

O

R CF3 F3C

O

O

R2

ð4Þ O

O n

24

Spiro-ortho-esters (SOE) of general formula 25, easily accessible from lactones by reaction with epibromohydrin (R = CH2Br) and further derivatization, undergo cationic polymerization. While at high temperatures (>100 C) a double ring-opening process to give poly(ether esters) 26 takes place, at low temperatures (<40 C) single ring opening of the ether ring to give poly(cyclic ortho-esters) (27) occurs (Scheme 7) <1994MM2380, 1997MI241, 1999JPS(A)2551>. This polymerization is reversible and the obtained polymers can be readily converted into the original monomers by treatment with acid catalysts at ambient temperature.

80

Functions Containing Three Chalcogens (and No Halogens) O O iii. >100 °C i, ii

n

n

O

O

O

O

n

R

iii. <40 °C

O O

m

26

R

O

n

25

O

O

i. Epibromohydrin; ii. derivatization; iii. cationic catalyst

R

m

27

Scheme 7

6.03.2.1.4

Ortho-esters from dioxacarbenium salts

Preparation of ortho-esters from carboxylic acid derivatives often proceeds via dioxacarbenium cation intermediates (cf. Section 6.03.2.1.3). The literature concerning dioxacarbenium tetrafluoroborates was duly reviewed in COFGT (1995) <1995COFGT(6)67>. Transformations requiring photoinduced electron transfer process involving dioxacarbenium ions will be discussed here. Electron transfer from acetonides, e.g., 2,2-dimethyl-1,3-dioxolane 28, to the singlet excited state of benzene 1,2,4,5-tetracarbonitrile followed by fragmentation of the donor radical cation gave methyl radical and dioxacarbenium cation 29 <1992JOC3051, 2001T555>, which by hydrolysis formed 2-hydroxyethyl acetate 31 via unstable ortho-acid 30. Methanolysis of 29 led to the formation of ortho-ester 32 (Scheme 8). This method was also applied for polyols and sugars <2001T555>.

O

NC

CN

NC

CN

+

O

MeCN hν

28

CN

O + + O CN–

NC

CN

29 H 2O MeOH

O

O

OH

O

O OH

O 31

O

O

30

32

Scheme 8

Compound 33, available in high yields from ninhydrin, was irradiated with fumarodinitrile in benzene for 5 h at 20 C to give racemic 6:7-benzo-anellated 4-oxaspiro[2.5]octane-trans-1,2-dicarbonitrile 34 in 32% yield <2002EJO2385>. The SOE 34 is the result of a cycloaddition of the dienophile with a dioxacarbenium ion intermediate (Equation (5)). CN O

O

CN O +

O O 33

NC

hν Benzene 32%

O

O CN O

O

O 34

ð5Þ

Functions Containing Three Chalcogens (and No Halogens) 6.03.2.1.5

81

Ortho-esters from 1,1-dialkoxyalkenes

Reaction of ketene dimethylacetal 36 with mono- and disaccharides led to cyclic ortho-esters at nonanomeric positions <1995CAR(267)227, 1998CAR(305)17>. For example 35 was transformed in 92% yield into 37 (Equation (6)). This sugar-protecting group can be selectively hydrolyzed under mild conditions. HO OH OH

O CH2=C(OMe)2

+

O OH

92%

OMe OH 35

MeO

PTSA, DMF

O

36

O OMe OH

ð6Þ

37

Substituted 2-alkoxyfurans 38 undergo dye-sensitized photo-oxygenation at low temperature (80 to 70 C) <1998SL17> to give 1-alkoxy-2,3,7-trioxabicyclo[2.2.1]hept-5-enes 39 (Equation (7)). R2

R3 R4

O

hν, –70 °C

R4

OR1

R2

R3 O O O 39

38

6.03.2.1.6

ð7Þ

OR1

Ortho-esters from 1,1-dialkoxycyclopropanes and related compounds

This method of ortho-esters preparation was completely reviewed in chapter 6.03 of COFGT (1995) <1995COFGT(6)67> and no substantial progress has been made since.

6.03.2.1.7

Ortho-esters from acetals

Reactive 2-phenylseleno acetals 40 (R1 = Bz, R2 = Ph or polystyrene), obtained from sugar glycosides by 1,2-selenium migration, can be transformed to ortho-esters 41 (path A comprising oxidative cleavage and ring closure, R3 = protecting group) and allyl ortho-esters 42 (path B including oxidative cleavage, ring closure, and Ferrier-type rearrangement, R3 = H) (Scheme 9) <2000AG(E)1089, 2000MI3149, 2000MI3166>.

O

O

OR1

SeR2 A O O

OR

B

3

40

O O

O

O R3O

R3O

42

41

Scheme 9

6.03.2.1.8

Ortho-esters from ortho-carbonate esters and trialkoxyacetonitriles

This method of ortho-esters preparation was completely reviewed in COFGT (1995) <1995COFGT(6)67> and no substantial progress has been reported since.

82 6.03.2.2 6.03.2.2.1

Functions Containing Three Chalcogens (and No Halogens) Preparation of Carboxylic Ortho-esters from Other Ortho-esters Trans-esterification reactions

Trans-ortho-esterification reactions with simple alcohols was duly reviewed in COFGT (1995) <1995COFGT(6)67> and only few improved methods have appeared since 1993. A series of chiral ortho-esters was prepared by re-esterification of triethyl ortho-acrylate with chiral substituted 1,2-diols in CH2Cl2 catalyzed by MgCl2 <1997TA139>. Similarly, 4,6-O(1-ethoxy-2-propenylidene)sucrose 43 was prepared from sucrose in anhydrous dimethlyformamide (DMF) in the presence of pyridinium p-toluenesulfonate (PPTS) at ambient temperature followed by acetylation of the crude reaction mixture <1993CAR(240)143>. 2-Ethoxymethyl- or 2-(2-methoxyethyl) propane-1,3-diol was heated with triethyl ortho-formate, -acetate, or -benzoate at 150 C to give 1,3-dioxane derivatives 44 <1994CJC2084>. OEt O O AcO AcO

O O

AcO O O AcO

R1

R2 OEt O

1

R = EtOCH2, MeOCH2CH2

OAc OAc

R2 = H, Me, Ph 44

43

Equilibrium polymerization reaction, as was shown in Section 6.03.2.1.3, can be also regarded as a trans-ortho-esterification reaction <1994MM2380, 1997MI241, 1999JPS(A)2551>. A further example of polymerization re-esterification is the reaction of 8-substituted 1,6,10-trioxaspiro[4.5]decane 45 in the presence of boron trifluoride diethyl etherate to give poly(cyclic orthoester) 46 as the intermediate (Scheme 10) during polymerization to the corresponding poly(ether esters) <1998JPS(A)2439>.

O O

BF3.Et 2O

R

R

O

O + O

O–

45

O O R

R

O O

O

O

O O O

O O

–

O

O

R

R

n

R

O + O

46

Scheme 10

Certain progress from 1993 is obvious in the chemistry of bicyclic ortho-esters of general formula 47 (e.g., OBO = 2,6,7-trioxabicyclo[2.2.2]octan-1-yl derivatives 47, R2 = H) and tricyclic ortho-esters 48, which are often used as alcohol or carboxyl protecting groups. R1

R2

O

O O

R1

O

47

O O 48

83

Functions Containing Three Chalcogens (and No Halogens)

Trans-ortho-esterification reactions of glycerol, 2-hydroxymethyl-2-methylpropane-1,3-diol, or 2,2-bis(hydroxymethyl)propane-1,3-diol with triethyl ortho-formate, -acetate, and -propionate were carried out at 100–140 C in the presence of an acid catalyst to obtain OBO derivatives <2002MI225>. The best result, a yield of about 90%, was obtained in the reaction of pentaerythritol with triethyl ortho-propionate in diglyme. The bulky OBO ester function has been shown to be a useful protecting group of amino acids e.g., aspartic or glutamic acid, for preventing epimerization at the -carbon and to induce good diastereoselectivities, e.g., in diazomethane cycloadditions <1999JOC8958, 2003MI36>. 1,2,5-Ortho-esters of D-arabinose <2002EJO3864> and a 1,2,6-ortho-ester of mannose <1999TL6423> have been described and their use in the glycosylation reaction has been studied. Tricyclic ortho-esters have been used for regioselective protection of polyalcohols <2000TL4185, 2002CAR(337)2399>. Thus, 4,6-di-O-benzyl-myo-inositol 50 was conveniently prepared via 1,3,5-ortho-ester 49, obtained by transesterification from ortho-formates or -acetates <2001CAR(330)409, 2002MI63> (Scheme 11).

R HO HO HO

OH

OH OH

i. DMF, RC(OEt)3 ii. Py, BzCl BzO R = H, Me

O

O O BzO 49

OH

i. DMF, Ag2O, BnBr ii. MeOH, i-BuNH2

R HO HO HO

O

TFA, H2O

OBn OH OBn

O O

HO BnO

50

OBn

Scheme 11

6.03.2.2.2

Modification of R1 and R2 of R1C (OR2)3

This method of ortho-ester preparation was completely reviewed in COFGT (1995) <1995COFGT(6)67>. 1,1,1-Triethoxypropyne 51 was prepared in 77% yield from trimethylsilylacetylene and triethoxycarbenium tetrafluoroborate in two steps <1997TL6803> (Scheme 12).

i. BuLi

OEt

–

TMS

ii. (EtO)3C+BF4

TMS

OEt OEt

i. BuLi ii. H2O

OEt OEt OEt 51

Scheme 12

As one example of the R2 modification, the radical addition of dithiols (R =(CH2)3, (CH2)6, or CH2C6H4CH2) to polymer 52, carried out at 20 C in the presence of 2,20 -azobisisobutyronitrile (AIBN) under ultraviolet (UV) irradiation in benzene for 4 h, affords the corresponding crosslinked poly(cyclic ortho-esters), which could be depolymerized to bifunctional monomers 53 (Scheme 13) <1997MI241>.

84

Functions Containing Three Chalcogens (and No Halogens) O 5O

HS-R-SH AIBN, hν

O 5O

O

O O O n

S R S

O

S R S

TFA, CH2Cl2

O

2n 52

O

O O

O

5O

53

n

Scheme 13

6.03.3

FUNCTIONS BEARING THREE SULFUR ATOMS

6.03.3.1

Methods for the Preparation of Trithio-ortho-esters and Related Compounds

6.03.3.1.1

Trithio-ortho-esters from RC(X1)(X2)X3

(i) From 1,1,1-trihaloalkanes This methodology using trihaloalkanes (X1 = X2 = X3 = halogen) was duly covered in COFGT (1995) <1995COFGT(6)67>. The reaction has been frequently used for preparation of both trialkyl and triaryl trithio-ortho-formates. Usually the reaction is done in the presence of a strong base. However, in the case of polyfluorothiophenol, extensive polymerization was observed under basic conditions. The reaction of pentafluorothiophenol 54 with iodoform in DMF was performed without any base providing tris(pentafluorophenylsulfanyl)methane 55, besides some polymeric products <1971TL2475>. Attempts to improve the reaction of 54 with chloroform and tetrachloromethane by the presence of AlCl3 led mainly to diarylated products 56, together with 57. Only small amounts of the expected triarylated compound 55 were formed <1999JFC(98)17> (Scheme 14). F F

CHI3, DMF

F

F

F

S F

F

F

CH 3

55

SH F

F

X-CCl3, AlCl3 X = H, Cl

54

F

F

F

F

S F

F

CXCl +

F

F F

2

+

S F

55

2

57

56

Scheme 14

(ii) From -halodithioacetals and ,-dihalothioethers -Chlorodithioacetal 58 treated with methanethiol provided the corresponding product 59 <1997AJC683> (Equation (8)). O Me

O

O S

S

SMe

MeSH

Me

O S

S

SMe

Cl 58

SMe

59

ð8Þ

Functions Containing Three Chalcogens (and No Halogens)

85

Similarly, alkylation of thiophenol with chloro derivative 61 generated in situ from 1,3-dithiane 60 gave 44% yield of 62 <1994SL547> (Scheme 15).

NCS S

S

S 60

S

PhSH 44 %

S

S

Cl

SPh

61

62

Scheme 15

Easily obtained dibromo derivative 63 treated with ethanethiol in the presence of silver triflate gave 91% yield of 64 <1996CAR(282)237> (Equation (9)). Br

S

S

Br OAc

AcO

EtSH, TfOAg 91%

ð9Þ

OAc

63

6.03.3.1.2

SEt OAc

AcO

OAc

SEt

64

Trithio-ortho-esters from thioimidate esters salts

This part covering reactions shown in Equation (10) was duly reviewed in chapter 6.03 in COFGT (1995) <1995COFGT(6)67> and no substantial progress has been achieved since. SR2 R1

R3SH + –

R1

NH2 X

6.03.3.1.3

SR3 SR3 SR3

ð10Þ

Trithio-ortho-esters from carboxylic acids and derivatives

As summarized in COFGT (1995) <1995COFGT(6)67>, acyl chlorides bearing no -hydrogen atom with thiols in the presence of suitable catalysts, e.g., ZnCl2 or AlCl3, provide acceptable yields of the corresponding trithio-ortho-esters. The method was used with various chlorides of aromatic carboxylic acids <1986TL4861, 1997JOC2917>.

6.03.3.1.4

Trithio-ortho-esters from dithia- and trithiacarbenium salts

Addition of thiols or other suitable sulfur nucleophiles to dithia- and trithiacarbenium salts was reviewed in COFGT (1995) <1995COFGT(6)67>. Regarding the reaction with dithiocarbenium salts, no progress has been made since. Trithiocarbenium salts are often generated from the corresponding trithiocarbonates and their reactions and progress in this field is covered in Section 6.03.3.1.6.

6.03.3.1.5

Trithio-ortho-esters from dithioacetals

The most common procedure converts dithioacetals by deprotonation with a strong base to a metallated intermediate, which upon treatment with a disulfide provides the final trithio-orthoesters. The procedure was summarized in COFGT (1995) <1995COFGT(6)67>. Similar conditions were also used for the preparation of tris(trifluoromethylsulfanyl)methyl cyanide 66 from 65 using either the corresponding sulfenyl chloride or disulfide <1994CB449> (Equation (11)). F3CS CN F3CS 65

i. NaH ii. CF3SCl or (CF3S–)2

F3CS SCF3 CN F3CS 66

ð11Þ

86

Functions Containing Three Chalcogens (and No Halogens)

Trimethylsilyl tetrathiophosphate 67 treated with dithioacetal 68 gave 69 <1994ZOB1333> (Equation (12)).

6.03.3.1.6

S P S SiMe3 EtS SEt

+ H2C(SEt)2

67

68

S P S EtS SEt

SEt

ð12Þ

SEt

69

Trithio-ortho-formates from trithiocarbonates

As reviewed in <1995COFGT(6)67>, trithiocarbonates treated with alkyllithiums at 78 C followed by quenching with an acid provided the corresponding trithio-ortho-formates. The methodology was later extended to the six-membered 1,3-dithiane 70 and compound 71 was prepared by this method (Scheme 16). When the intermediate anion was treated with an alkylating agent before the quenching, high yields (75–89%) of substituted analogs 72 were obtained. When the mixture was allowed to reach ambient temperature before the quenching, the corresponding thioacetals 73 and 74 were formed <1991CL1315>. i. BuLi, rt ii. H+

S

i. BuLi, –78 °C ii. H+

S

Bu

S i. BuLi, rt ii. RX, 0 °C iii. H+

S 73 S

Bu

S

R

S 70

S SBu

i. BuLi, –78 °C ii. RX iii. H+

S 71

R = Me, Et, Pr, i-Pr, Bu

74

S

SBu

S

R

72

Scheme 16

Compound 75, prepared by the above-mentioned method, was deprotonated with methyllithium and the formed anion 76 was treated with dithione 77 and then with an excess of iodomethane to give an acceptable yield of complex structure 78 <1996SM175> (Scheme 17).

BuS

BuS

S

S

SMe BuS

S 75

BuS

Li+ –

SMe

S 76

OMe S

S

S

S

i. S

S

55%

OMe 77

ii. MeI

SMe S

BuS

S

BuS

SMeS S

OMe SMe

S

SBu

S S MeS

SBu

S

OMe 78

Scheme 17

Fluorine ion-induced reaction of allyl and benzyl silanes with both linear and cyclic trithiocarbonates provided good yields of the corresponding trithio-ortho-esters <1994TL161> (Equations (13) and (14)).

87

Functions Containing Three Chalcogens (and No Halogens) S + Ph SPh

PhS

TBAF 67%

SiMe3

S PhS

S S

SiMe3

+

S

TBAF 71%

Ph

ð13Þ

SPh S

ð14Þ S

S

Readily available oxazolidinone derivative 79, as an equivalent of stabilized oxomethine ylide 80, reacted with trithiocarbonate 81 as dipolarophile giving cycloadduct 82 as a racemate and only the shown regioisomer was detected (Scheme 18). Derivatives of 79 bearing at C-6 t-butyldimethylsilyl (TBDMS)-protected (R)--hydroxyethyl substituent gave the corresponding cycloadduct in only 20% yield <1997JOC3438>. S H

MeS

O O

N O

MeCN 80 °C

O

N

+ –

CO2PNB

H

SMe

S

81

N

60%

O

SMe CO2PNB

CO2PNB 79

SMe

82

80

Scheme 18

One of the methods frequently used for the synthesis of 2-alkylsulfanyl-1,3-dithiole derivatives 85 is shown in Scheme 19. The method is based on reduction of alkylsulfanyl-1,3-dithiolium salts 84, easily obtained from the corresponding 1,3-dithiole-2-thiones 83 <1994JOC5324, 1994JOC6519, 1996JCS(P1)783, 1996SM175, 1997JOC1903, 1997S26, 1998CC361, 1998JMAC1185, 2001EJO933, 2001MI145, 2001SM97, 2002JMAC2137>. R1

S S

R2

R1

R3X

S

R2

83

– S X SR3 + S

R1

S

R2

S

SR3

84

85

Scheme 19

Alkylation of 83 is done with common alkylation agents, e.g., iodomethane <1994JOC6519>, dialkyl sulfate followed by tetrafluoroboric acid <1996JCS(P1)783, 1997S26, 2001MI145>, methyl triflate <1994JOC5324, 1997JOC1903, 1998CC361, 1998JMAC1185, 2001EJO933, 2001SM97, 2002JMAC2137>, or dimethoxycarbenium tetrafluoroborate formed in situ from ortho-formate and boron trifluoride diethyl etherate <1996SM175>. Yields of the corresponding dithiolium salts are frequently nearly quantitative. The reduction step is usually done with sodium borohydride and yields are also usually high, very often over 90%. Only very rarely did the borohydride reduction lead to decomposition and use of sodium cyanoborohydride was necessary <1994JOC5324, 2001EJO933>. Compounds 85 are of a great interest since they are intermediates of fulvane derivatives studied as perspective synthetic materials. Besides the mentioned references, there are many others using the same procedure without isolating the 2-alkylsulfanyl-1,3-dithiole intermediates. Some interesting structures, for example crown ether derivative 86 <2001EJO933> and [60]fullerene derivative 87 <2002JMAC2137> have been synthesized by this method. O O

S

S

S SMe

O

S

SMe

S

S

O 86

87

88

Functions Containing Three Chalcogens (and No Halogens)

Dithiolium salts, e.g., 88, can be reduced with zinc to give the corresponding dimeric products, e.g., 89 <1990KGS471> (Equation (15)). S X S

S + S

X– Zn

SEt

S

S SEt S

S

S

S EtS S

S

X

X

X = CO, O, S 88

ð15Þ

89

The triflate salt of 84 reacted with anions generated in situ from anthrone <1999OL2005> or cyclononatetraene <1994HCA1377> with lithium diisopropylcyclohexylamide (LDA) to give compounds 90 and 91, respectively. R1

R2

S

S SMe

S

S SMe

O 91

90

6.03.3.1.7

Trithio-ortho-formates from tetrathio-ortho-carbonates

Seebach has reported transformation of tetrathio-ortho-carbonate to trithio-ortho-formate by treatment with BuLi at low temperature followed by quenching with water <1967AG(E)443> and the method has been used several times since <1995COFGT(6)67>. Arsenic pentafluoride oxidized (F3CS)4C to the stable salt (F3CS)3C+AsF 6 92, which treated with halide ions provided good-to-excellent yields of the corresponding trithio-ortho-esters 93. Under the described reaction conditions using potassium iodide, the oxidation product 94 was obtained in 86% yield <1994CB597> (Scheme 20).

2 (F3CS)4C + 3AsF5

SO2

2 (F3CS)4C+ AsF–6 + AsF3 + F3CS-SCF3 92

X–

KI 86 %

F3CS F3CS F3CS

X

F3CS F3CS F3CS

SCF3 SCF3 SCF3

X = F, Cl, Br 93

94

Scheme 20

6.03.3.1.8

Miscellaneous

2-Methoxy-1,3-dithiolane 95 with silylated thymine did not provide the expected 1,3-dithiolan2-yl nucleoside but 1,2-bis(1,3-dithiolan-2-yl)dithioethane 96 was obtained in 92% yield instead <1996JOC3611> (Equation (16)). This compound can also be obtained from trialkyl orthoformates and ethanedithiol <1972HCA75>.

89

Functions Containing Three Chalcogens (and No Halogens) S

S 3

OMe S

2

92%

S

S S

ð16Þ

S

S

95

96

Addition of thiols to quinone methides 97 provided the corresponding trithio-ortho-esters 98 in yields between 44% and 99% <1995PS(107)119> (Equation (17)). OH

O Me

Me

Me R

Me

3SH

ð17Þ R1S

R1S

SR2

SR3

97

6.03.3.2 6.03.3.2.1

SR2

98

Preparation of Trithio-ortho-esters from Other Trithio-ortho-esters Higher trithio-ortho-esters from trithio-ortho-formate esters

Transformation of trithio-ortho-esters, mainly via the corresponding lithium salts, has become one of the most important methods of preparation of higher trithio-ortho-esters. The lithium salts are usually generated by BuLi at 78 C as described by Seebach <1967AG(E)443, 1969S17, 1972CB487, 1972CB3280>. Selected examples of utilization of such lithium salts are given below.

(i) Alkylation with alkyl halides or triflates Alkylation of LiC(SMe)3 with a wide range of alkyl halides provided good yields of the corresponding trithio-ortho-esters, which were used as intermediates of the synthesis of methyl thiolcarboxylates <1993JCS(P1)2075>. Alkylation of LiC(SMe)3 with 4-bromobutyric acid provided quantitative yield of 5-tris(methylsulfanyl)pentanoic acid <2000JOC235>. Similar alkylation with 1-azido-3-iodopropane led to 91% yield of the corresponding azido derivative, which was used in the synthesis of a reversed thioester analog of acetyl-coenzyme A <1998JA3275>. Nucleophilic displacement of allylic chloride 99 with LiC(SMe)3 at low temperature led to an excellent yield of alkylated trithio-ortho-ester 100, which was utilized as a carboxyl anion equivalent to the synthesis of ester 101 <1994JOC4853> (Scheme 21).

LiC(SMe)3 THP-O 99

Cl

97%

THP-O

C(SMe)3 100 55 %

THP-O

COOMe 101

Scheme 21

Similarly, high yields of sartane analog 102 <1994TL9391> as well as pyran derivative 103 <2002CEJ1670> were obtained by the reaction of suitable lithium salts with the corresponding iodo and triflate derivatives, respectively.

90

Functions Containing Three Chalcogens (and No Halogens) Cl N O-TBDMS

Bu

SMe SMe SMe

O

N Ar

S

O

SMe S

O

102

103

(ii) Reaction with aldehydes and ketones Tris(alkylsulfanyl)methyllithiums are known to react with a wide range of aldehydes from simple ones e.g., 3-hydroxy-2,2-dimethylpropionaldehyde <1999JOC2903>, 6-isopropyl-3-methylhept-6en-1-al <1996JCS(P1)349>, pentadec-5-en-1-al <1998TL3115>, to much more complex aldehydes derived from amino acids <1995BMC1063> or sugars <1999SC3841, 2000TL307>. Usually good-to-high yields of the respective hydroxy derivatives 104 are obtained. The formed hydroxy derivatives are either isolated, or in situ oxidized to the corresponding oxo derivatives 105 <2001JOC5822>, or alkylated to their O-alkyl derivatives 106 <1998TL3115>. Hydroxy trithio-ortho-esters 104 are often transformed to various carboxylic acid derivatives e.g., 107 or 108 (Scheme 22) in the following steps. O R

C(SMe)3 105 OMe

R

C(SMe)3 106

OH R-CHO + (MeS)3CLi R

OH

C(SMe)3 R

104

COOMe 107 OH

SMe

R O 108

R = CH2=CH-, HOCH2CMe2-, Me2CHC(=CH2)CH2CH2CHMeCH2-, Me(CH2)8CH=CH(CH2)3CHO

Scheme 22

In spite of the report on the 1,2-addition of LiC(SMe)3 on acrolein <2001JOC5822>, a different paper reported that reaction of LiC(SPh)3 with acrolein gave the 1,2- and 1,4-adducts in a 3:5 ratio <1995TL8925>. In the case of chiral compounds, the stereoselectivity of this reaction varies <1995BMC1063, 1996JOC6685, 1997JOC3880, 1999SC3841, 2000TL307> and only rarely is one stereoisomer obtained. This is the case when bulky LiC(SPh)3 reacted with protected aldehyde 109 where L-ido derivative 110 was obtained as the only isomer in 92% yield <2000TL307> (Equation (18)).

CHO OBn O O 109

LiC(SPh)3 O

C(SPh)3 OH OBn O

92%

O 110

O

ð18Þ

Functions Containing Three Chalcogens (and No Halogens)

91

In the case of ketone 111, the reaction is stereoselective even for LiC(SMe)3 giving 94% of the isomer 112 (Equation (19)). No 1,4-addition was observed <1996JOC6685>. High yield (78%) and similar stereoselectivity was also reported for the reaction of (S)-2-acetylpyrrolidine trifluoroacetate with an excess of LiC(SMe)3 <1997JA6984>. O

OBn

O

O

O LiC(MeS)3

OBn OH

O

C(SMe)3

94%

ð19Þ

O

O 111

112

(iii) Reaction with epoxides Terminal epoxides generally react with LiC(SPh)3 to give only low yields of -hydroxy trithioortho-formates <1967AG(E)443, 1972CB487>. However, a modification of this method using LiC(SMe)3 is reported to give good-to-excellent yields of 113, which can be easily converted to -hydroxyesters <1993SC811> (Equation (20)). O

OH

LiC(MeS)3

R

R

C(SMe)3

ð20Þ

113 R = Me, PhO, PhCH2O

(iv) Reaction with ,-unsaturated ketones or esters Addition of sulfur stabilized carbanions e.g., LiC(SPh)3, to unhindered ,-unsaturated ketones has been reported to produce high yields of the 1,4-addition products <1975CC216, 1977TL3549, 1990JOC1198, 1990JOC2132>. The ready availability of such adducts combined with the variety of possible transformations of the trithio-ortho-ester unit make the reaction potentially useful. The same reaction with exocyclic derivative 114 provided only 24% yield of the product. However, when the reaction was done in the presence of trimethylsilyl chloride (TMSCl), the yield was substantially improved and 75% yield of 115 was obtained (Equation (21)). The same modification was found useful also with noncyclic compounds 116 and the corresponding ketones or esters 117 were obtained in good yields <1995TL8925> (Equation (22)). C(SPh)3

TMSCl, LiC(SPh)3

O

75%

114

115

O

O

TMSCl, LiC(SPh)3

R 116

ð21Þ

O

R = Me, 96% R = OMe, 69%

(PhS)3C

R

ð22Þ

117

Cyclic ,-unsaturated lactones add lithiated trithio-ortho-esters to the ,-double bond to give the corresponding lithium salts 119. This reaction was described for several -angelicalactone derivatives 118, the formed lithium salts can be either quenched with aqueous solutions to give the corresponding saturated compounds 120 <1995JOC5628, 2003BMC357>, or further alkylated to 121 <1994TL4123, 1995JOC5628>, or transformed by reaction with tosyl azide to the corresponding azides 122 <1999JOC2657> (Scheme 23). Enantioselective synthesis of R-2-methyl-1,4-butanediol from 5R-(1-menthyloxy)-5-furan-2-one based on the Michael addition of LiC(SPh)3 and the following Raney nickel desulfuration has been reported <1992SC1367>.

92

Functions Containing Three Chalcogens (and No Halogens) (PhS)3C R (PhS)3C

Li

O 120

O

(PhS)3C

(PhS)3CLi R

O

O

R

118

O

O

R

119 R = Me, Bu, TBDPS-O

O 121

(PhS)3C R

O

N3 O

O

122

Scheme 23

Nucleophilic addition of LiC(SMe)3 to carbaldehyde-derived 2,3-dihydro-4H-pyran-4-one 123 yielded a mixture of both 1,2- and 1,4-addition products 124 and 125, respectively. Depending on the conformation on the C-2 atom, either 1,2- or 1,4-adducts were preferentially formed <1997T7867> (Equation (23)). O

BnO

HO BnO

LiC(SMe)3

BnO

BnO

O 123

O

C(SMe)3 BnO

+

BnO

O

124

O

C(SMe)3

ð23Þ

125

Tricyclic xanthone derivative 126 added LiC(SMe)3 in a 1,4-manner to give 35% of product 127 <1997JCS(P1)1819> (Equation (24)). O

O

O

OH

LiC(SMe)3

O 126

ð24Þ

35%

O

C(SMe)3

127

Addition of LiC(SMe)3 to methyl acrylate gave 40% yield of methyl 4,4,4-tris(methylsulfanyl)butyrate <2000JOC235>.

(v) Reaction with carboxylic derivatives Tris(alkylsulfanyl)methyllithiums are known to react with both aliphatic <1995JOC6017> and aromatic <1995JOC6017, 1996JOC9572, 1996S467, 2001TL8189, 2002S921> carboxylic acid esters to provide 128. The reports showed that the reaction should be optimized to suppress formation of side products to provide good yields of the desired products. In particular, aromatic derivatives are versatile intermediates in the synthesis of aryl bis(alkylsulfanyl)thioacetates 129 <1997JOC7228, 2002S921>, -ketothioesters 130 <1996S467, 2001TL8189> or -ketoacids 131 <2001TL8189> (Scheme 24). Similar reaction of LiC(SMe)3 with other carboxylic acid derivatives such as acyl chlorides, anhydrides, or thioesters leading to variable yields of identical products have also been described. The yields of the required products were substantially enhanced when N-(methylsulfanyl)phthalimide was used in the work-up procedure <1996JOC9572>.

93

Functions Containing Three Chalcogens (and No Halogens) RS

SR SR

Ar

O Ar

O

LiC(SR)3 Ar

OMe

O 129 O SR

Ar

C(SR)3 128

O 130 O Ar

COOH 131

Scheme 24

(vi) Miscellaneous Azulene treated with LiC(SMe)3 gave intermediate 132, which was oxidized with chloranil to provide practically quantitative yield of crude derivative 133 <2001S1346> (Scheme 25).

LiC(SMe)3

C(SMe)3

Chloranil quant.

C(SMe)3

132

133

Scheme 25

6.03.3.2.2

Trans-esterification of trithio-ortho-esters

No substantial achievements have been reported since COFGT (1995) <1995COFGT(6)67> was published.

(i) Modification of R1 and R2 of R1C (SR2)3 Bromine–lithium exchange of trithio-ortho-ester 134 was used to generate the corresponding lithium salt <1980JOC740>, which after the treatment with tris(perfluorodecylethyl)silyl bromide gave fluorous trithio-ortho-ester 135 <1997JOC2917> (Equation (25)). PrS

SPr SPr

PrS

i. BuLi ii. (C 10F21CH2CH2)3SiBr

SPr SPr

ð25Þ

(C10F21CH2CH2)3Si

Br 134

135

Various substituent modifications were done with cyano derivative 66, which can be prepared either from 65 (Section 6.03.3.1.5) or by alkylation of silver cyanide with bromo derivative 136. Acidic hydrolysis of 66 with sulfuric acid provided nearly quantitatively the corresponding amide 137. Its treatment with oxalyl chloride provided either 138 or 139, depending on the ratio of the reactants, while similar treatment with phosgene failed <1994CB449> (Scheme 26).

94

Functions Containing Three Chalcogens (and No Halogens) F3CS F3CS F3CS

O

F3CS F3CS F3CS

AgCN

Br

136

CN

H2SO4

F3CS F3CS

97 %

NH2 SCF3 137

66 0.5 equiv. (COCl)2

O F3CS F3CS

SCF3

O N H

70% 1 equiv. (COCl)2

60%

O

O SCF3 SCF3 SCF3

N H

F3CS F3CS

N C O SCF3

138

139

Scheme 26

6.03.3.3 6.03.3.3.1

Methods for the Preparation of Oxidized Derivatives of Trithio-ortho-esters Oxidized trithio-ortho-esters containing at least one sulfoxide group

Sulfoxide 140 treated with LDA and methyldisulfanylmethane provided 70% of 141 as the only isolated product <1998BMCL3331> (Equation (26)). MOM-O

MOM-O

O S

H2N

O S

LDA, MeSSMe

H2N

70%

Me

SMe

ð26Þ

SMe

140

141

Reaction of trithiocarbonates 142 with 3-chloroperoxybenzoic acid (MCPBA) afforded the corresponding S-oxides 143, which reacted with organolithium compounds, e.g., methyllithium, at low temperatures in a thiophilic manner to give carbanions 144 stabilized by three sulfur atoms <1997T1323>. Hydrolysis afforded trithio-ortho-ester oxides 145 which are unstable at ambient temperature. For unsymmetrical trithiocarbonates 142, a 1:1 mixture of both possible diastereoisomers was obtained. Carbanions 144 can also be trapped by other electrophiles, e.g., iodomethane in the presence of hexamethylphosphoramide (HMPA) provided 94% of 146. Addition of the anion to enones provided either unstable adducts 147 or directly their degradation products 148 (Scheme 27). S R1S

S

MCPBA SR2

R1S

142

O

MeLi

SR2

Me

R1S – SR2

143

144

MeCH=CH-CHO Me – R3SOH

R1S O R2S

Me 148

O

S

O Me S R1S

Me SR2

147

Me O

Me R1S

S

MeI

H2O

O Me SR2

Me

146

S

R1S

O SR2

145

Scheme 27

Generation of the corresponding bridgehead carbanion from 149 followed by treatment with iodoalkanes provided no expected substituted trithiolanes and the reaction led to unexpected products, the nature of which was strongly dependent on the electrophile added. When the anion was treated with iodomethane or iodoethane, compounds 150 were isolated and their structure was proved by X-ray crystallography. However, less reactive 2-bromopropane did not react at 78 C and at room temperature provided compound 151 <1999T10341> (Scheme 28).

95

Functions Containing Three Chalcogens (and No Halogens)

Ph

O S S

O i. LDA, THF, –78 °C S S S ii. 2-PrBr, rt S H S Ph

i. LDA, THF, –78 °C SR ii. RI, –78 °C Ph 79–90 %

150

149

S

O

151

Scheme 28

Silanes have also been successfully used as alternative nucleophiles for the thiophilic addition. S-Oxide 152 treated with allyl and benzyl trimethylsilane in the presence of tetrabutylammonium fluoride provided 38–41% yields of the respective products 153 <1997T1323> (Equation (27)). S S

R

O 38–41%

S

O

S

RSiMe3, TBAF

S

152

ð27Þ

S

153

Oxidation of triaryl trithio-ortho-esters with organic peroxy acids leading to triaryl sulfoxides is well known. Asymmetric oxidation of 2-phenylsulfanyl-1,3-dithiane 154 using modified Sharpless conditions led to 65% yield of the corresponding anti-R-oxide 155 but the enantiomeric excess (ee) achieved was poor (Equation (28)). No exocyclic oxidation was observed either for compound 154 or for the similar methylsulfanyl derivative <1996T2125>.

S

Ti(O-i Pr)4, DET, TBHP

S

S

S

+

65%

SPh

ð28Þ

SPh

154

6.03.3.3.2

–

O

155

Oxidized trithio-ortho-esters containing at least one sulfone group

Treatment of 2-lithium-1,3-dithiane 156 with tosyl azide gave no dimer 157 but instead low yield of the corresponding 2-tosyl derivative 158 was obtained, together with major amounts of unidentified products <1997T9269> (Scheme 29). S

S

S Li

S

S

S

157

TosN3

S

17%

S

156

Tos 158

Scheme 29

2,5-Norbornadiene 159a and 2,5-norbornene 159b were added in diffuse daylight C-sulfonyldithioformate 160 in a [2 +2] fashion to give 161a (92%) and 161b (80%), respectively (Equation (29)). The compounds in crystalline form are stable in the dark <1995SUL(19)29>. Similar treatment of 160 with hex-1-ene provided the corresponding ene-reaction product <1995SUL(19)59> 162. Thermal reaction of 160 with tetramethylallene provided more than 90% yields of the corresponding ene-products (Equation (30)). S + 159a,b

R1S

S

R2

O O 160

hν

S

80–92%

SO2R2 R1S 161a,b

ð29Þ

96

Functions Containing Three Chalcogens (and No Halogens)

S +

R1S

S O

S

hν 80%

R2

1

R S

O

R2

S O

ð30Þ

O

160

162

Sulfonyldithioformates 160 treated with dienes, e.g., cyclopentadiene or substituted butadienes, provided good yields of the corresponding adducts, e.g., 163 <1995SUL(18)215> (Equation (31)). S +

1

R S

R2

S O

R2O2S

O

R1S 163

160

ð31Þ

S

Allyldithiobenzoate 164 was oxidized by air oxygen to provide, beside the allyl thiobenzoate 166, also 1-phenyl-2,6,7-trithiabicyclo[2.2.1]heptane-2,2-oxide 165 at a rate of 7% a month (Equation (32)). The structure was proved by X-ray diffraction but the total yield achieved was not given <1995SUL(18)67, 1995T11503>. S Ph

S

air O2

S

S

+ S Ph O O Ph

164

165

O

ð32Þ

S 166

Bis(methanesulfonyl) (ethylsulfanyl)methane 168, also easily available from bis(methanesulfonyl)methane, was prepared in 87% yield by treatment of 167 with sodium ethanethiolate. Compound 168 treated with 2 equiv. of BuLi followed by iodopentane provided monoalkylation product 169 and dialkylation product 170 in 76% and 17% yields, respectively <2002TL1377> (Scheme 30). O OO O S S Me (CH2)5Me EtS H O OO O S S Me Me EtS SEt

O OO O S S Me Me EtS H

EtSNa, NaH 87%

167

i. 2equiv. BuLi ii. Me(CH2)4I

169 76% +

O OO O S S Me(CH2)5 (CH2)5Me EtS H 170 17%

168

Scheme 30

Though oxidation of hexathiaadamantane derivative 171 with 2 equiv. of MCPBA provided a complex mixture of mono-, bis-, and tris-S-oxides, the same reaction with 25 equiv. of MCPBA or MnO2 led to regioselective formation of 172, which was obtained in 69% and 60% yields as the only detectable product <2000JCS(P2)1777> (Equation (33)).

S S S

S S S

171

MCPBA, 69% MnO2, 60%

O2S S O 2S

SO2

ð33Þ

S SO2

172

Functions Containing Three Chalcogens (and No Halogens)

97

Sulfonylmethane derivative 173 treated with N-phenyltrifluoromethane sulfinimide in the presence of potassium bis(trimethylsilyl)amide provided 39% yield of 174 <1998JMC1092> (Equation (34)). O O S SMe

Cl

O OO O S S CF3 SMe

i. (Me3Si)2NK ii. PhN(SO2CF3)2 39%

Cl

173

ð34Þ

174

Trimethylsilylmethyllithium added smoothly to trifluoromethanesulfonyl, nonafluorobutanesulfonyl, tridecafluorohexanesulfonyl, and heptadecafluorooctanesulfonyl fluorides to provide the corresponding methane derivatives 175. Treatment of these compounds with 2 equiv. of BuLi followed by quenching of the generated dianions with one of the mentioned sulfonyl fluorides provided anion 176. The corresponding free acids 177 were obtained in high yields (72–95%) by vacuum sublimation from concentrated sulfuric acid (Scheme 31). A series of fluorous tris(perfluoroalkanesulfonyl)methanes was prepared in this way and catalytic activity of their lanthanide(III) salts was studied <1999JOC2910, 2000SL847, 2002T3835>.

i. 2 equiv. BuLi

O OO O S 1 1 S Rf Rf

2

ii. Rf SO2F

O OO O S S 1 – Rf + O S 2 Li Rf O 176

175

O OO O S S 1 Rf O S 2 Rf O 177

H2SO4

1

Rf

1 Rf

72–95%

Scheme 31

Reaction of 3 equiv. of nonafluorobutanesulfonyl fluoride with 4 equiv. of methylmagnesium chloride provided the corresponding magnesium salt 178 and its acidic hydrolysis gave 179 <1999SL1990> (Scheme 32).

C4F9SO2F

MeMgCl

(C4F9SO2)3CMgCl

O OO O S S C4F9 C4F9 O S C4F9 O

H2SO4

178

179

Scheme 32

The reaction of sulfinate anions with thiophosgene has been discovered <1980OPP229>. In the case of 1-adamantyl derivative 180, tris(adamantylsulfonyl)methane 181 was obtained in 39% yield <1992SUL(15)209> (Scheme 33).

AdSO2Na

CSCl2

(AdSO2)2CH-S-SO2Ad

180

–S 39%

O OO O S S Ad Ad O S Ad O 181

Scheme 33

6.03.3.3.3

Oxidized trithio-ortho-esters containing at least one sulfonate group

This was duly reviewed in COFGT (1995) <1995COFGT(6)67> and no substantial progress has appeared since its publication.

98 6.03.4

Functions Containing Three Chalcogens (and No Halogens) FUNCTIONS BEARING THREE SELENIUM ATOMS

6.03.4.1

Methods for the Preparation of Triseleno-ortho-esters

6.03.4.1.1

Triseleno-ortho-esters from triselenacarbenium salts

New examples documenting the usefulness of this method have been published <1996JOC2877>.

6.03.4.1.2

Triseleno-ortho-esters from diselenoacetals and related compounds

1,3-Diselenane 182 treated with BuLi and MeSeSeMe provided excellent yields of the corresponding triseleno-ortho-ester as a single cis-isomer 183 having the MeSe group in equatorial position. This compound treated with lithium diisopropylamide and then with MeOH or MeI provided good yields of the corresponding trans-derivatives 184 or 185 <1996TL8015> (Scheme 34). It was necessary to use potassium diisopropylamide (KDA) instead of BuLi to obtain similar PhSe derivative which was obtained in 92% as a mixture of cis-trans isomers in a ratio of 98:2 <1996TL2667>.

SeMe

Se Se

i. BuLi ii. MeSeSeMe 81%

182

i. LDA ii. MeOH

H Se SeMe Se 183

Se H Se

95%

184

i. LDA ii. MeI 93%

SeMe Se Me Se 185

Scheme 34

6.03.5

MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN

6.03.5.1 6.03.5.1.1

Methods for the Preparation of Functions R1C(OR2) (OR3)SR4 From R1C(X1)(X2)X3

(i) From ortho-esters Treatment of partially protected mercaptodioles or mercaptotrioles 186 with methyl orthoformate in the presence of p-toluenesulfonic acid provided high yields (78–85%) of 187 <1996JOC3604, 1997JHC909> (Equation (35)). OMe

OH TBDMSO

R

O

(MeO)3CH 78–85 %

S

TBDMSO

SH 186

R = H, TBDMSOCH2

ð35Þ

R 187

Reactions of electrophilic carbenes with thiocarbonyl compounds are believed to occur through intermediate thiocarbonyl ylides <2000PJC1503>. Dimethoxycarbene formed by thermolysis of oxadiazoline 188 was trapped with adamantanethione 189 to provide 92% yield of the first 2,2-dialkoxythiirane described 190 <2001OL2455> (Equation (36)).

Functions Containing Three Chalcogens (and No Halogens) MeO OMe N N

S

+

O

188

99

S OMe Heat 92%

OMe

189

ð36Þ

190

(ii) From ,-dihalothioethers Acetylated dibromo derivative 63 treated with methanol, ethanol, or allyl alcohol in the presence of silver triflate provided good yields of the corresponding acetylated o-thiolactones 191 <1996CAR(282)237> (Equation (37)). S

Br Br OAc

AcO

OR

S ROH, TfOAg

OR OAc

AcO

OAc

OAc R Yield (%) 90 a Me 69 b Et Allyl 70 c

63

ð37Þ

191

Treatment of trichloro derivatives 192 with Na2CO3 in methanol led to selective replacement of both geminal chloro atoms to afford dimethoxy derivatives 193 <1994JOC6973> (Equation (38)). O

O SR Na2CO3–MeOH

Cl

Cl

SR

Cl

MeO OMe

Cl

192

ð38Þ

193

(iii) From thioesters Ozonolysis of 194 and 196 in CH2Cl2 at 78 C followed by reduction with Me2S gave good yields of cage compounds 195 and 197, respectively <1997T17653> (Equations (39) and (40)). OAc

O i. O3, CH2Cl2 ii. Me2S

O

60–65 %

O

O R 194

O

ð39Þ

O R 195

CHO

O R 196

SMe

O O

SMe

i. O3, CH2Cl2 ii. Me2S

SMe

80–85 %

CHO O

SMe

O O

ð40Þ

O R 197

(iv) From dithioesters Aromatic dithioesters 198, which are easily available either from the appropriate nitriles or from the corresponding Grignard reagents, were transformed in high yields to 201 by treatment with sodium methoxide followed by iodomethane. Intermediate formation of 199 and 200 was supposed <1997MI3691, 2001T1289> (Scheme 35).

100

Functions Containing Three Chalcogens (and No Halogens)

S

S SR2

MeONa

MeO MeONa

OMe

R1

S–Na+ OMe

R1

R1 198

199

200

MeI

R1 = Me, CH2 = CH–; R2 = Me, CH2COOH

MeO

SMe OMe

R1 201

Scheme 35

6.03.5.1.2

Miscellaneous

Protected bromopyranones, e.g., 202 <1994BMC1309, 1998CAR(308)287, 2001JA3369> and furanones 204, <1999OL1517>, treated with ethanethiol in the presence of 2,6-lutidine or collidine, usually in nitromethane, provided high yields of 203 and 205, respectively. The similar phenylsulfanyl analog of 205 was found to be unstable <1999OL1517> (Scheme 36).

O

Br

AcO

OAc

O EtSH 82%

AcO

OAc

O

SEt

203

O2CTol

O

Me

OAc

202

Br

O

EtSH

O

86%

O2CTol

O

EtS O

O2CTol

O2CTol

TolCO2

204

205

Scheme 36

6.03.5.2 6.03.5.2.1

Methods for the Preparation of Functions R1C(OR2) (SR3)SR4 From R1C(X1)(X2)X3

Good yields of 2-methoxy-1,3-dithiane were prepared from 1,3-dithiane 60 by its sequential treatment with N-chlorosuccinimide (NCS) and methanol <1994SL547> (Scheme 37).

NCS S

S 60

S

S

MeOH

S

S

70% Cl 61

Scheme 37

OMe

101

Functions Containing Three Chalcogens (and No Halogens) 6.03.5.2.2

From dithiacarbenium salts

Hexathiaadamantane 171 in superacid media (e.g., CF3SO3H, FSO3H-SbF5, or H2SO4SO3) formed carbodication 206, which treated with ice provided oxa derivative 207 <1999OL1771, 2000JCS(P2)1777> (Scheme 38).

S S S

+ S S S + S S

S S S

171

S S

H2O 30%

S

206

O S S

207

Scheme 38

6.03.5.2.3

From dithioacetals and related compounds

Acid 208 treated with lead tetraacetate provided 60% yield of 209 <1994S167> (Equation (41)). CF3

CF3

Pb(OAc)4

S S

COOH

60%

S O

ð41Þ O

209

208

6.03.5.2.4

S

From ketene dithioacetals

Intramolecular acid-catalyzed cycloaddition of hydroxysubstituted cyclic ketene dithioacetals was first described by Corey and Beames as a method of lactone protection <1973JA5829>. Though the methodology is undoubtedly important, it was not mentioned in the corresponding chapter of COFGT (1995) <1995COFGT(6)67>. Therefore, some principal older papers will be also reviewed here. Reviews on the ketene dithioacetals are also available <1977S357, 1990S171>. Several useful applications of this cyclization protocol have been described since <1986JA5221, 1992JCS(P1)1901, 1993TL1035, 1993TL1039, 1996S285, 1997JOC9107, 1998JCS(P1)9>. This reaction is a key step frequently used in the synthesis of a range of naturally occurring compounds. Transformation of mevinoline to its homolactone using ketene dithioacetal has been described <1982JOC4750>. This method was also used for the stereoselective synthesis of a range of -alkyl--butyrolactones 210 (Scheme 39). The method was also ˜ modified for the stereoselective synthesis of ,-bis-functionalized -butyrolactones <1993JOC2725>. OH S R

S

TFA–CH2Cl2 71–95 %

R

S O S

HgCl2–aq. MeCN

R O O 210

Scheme 39

Similarly, the cyclization can also be used for the synthesis of functionalized -lactones with remote asymmetric induction. Acid-catalyzed cyclization of ketene dithioacetals 211 by HCl/ CH2Cl2 gave predominantly the -isomers of the bicyclic dithio-ortho-esters 212 (Equation (42)). Hydrolysis (HgCl2, pH 7) then gave the corresponding lactones <1986JA5221, 1986TL3661>. High yield of spirocyclic compound 214 with acceptable diastereomeric ratio (12:1) was also obtained by acidic cyclization of 213 (Equation (43)). The compound was used as an intermediate of the salinomycin synthesis <1998JCS(P1)9>. A similar procedure was also used in the synthesis of a key synthetic fragment of rapamycin <1996SL903>.

102

Functions Containing Three Chalcogens (and No Halogens) OSiMe3 R

BOM S

R S

HCl–CH2Cl2 76% (R = H) 92% (R = Me)

S

BOM

H

211

O

ð42Þ

S

212

Et

HO

OH

HCl–CH2Cl2

HO S

S

81%

S

Et

H

213

ð43Þ

O

S

214

Even higher diastereoselection was reported in case of compound 215, where the stereocontrol was by bromine and oxazolidine moieties <1996S285> (Equation (44)).

S

S

Bn Br

S

S O

0 °C, 18 h

N

O

O

ð44Þ

N

H

O

OH O

O

47%

O

Br Bn 215

Lactols 216 and 218 on reaction with 2-lithio-2-trimethylsilyl-1,3-dithiane followed by acidic treatment afforded high yields of 217 <1994TA247> and 219 <1996SL925> (Equations (45) and (46)). MOMO BDPSO

OH

O OMOM

Me3Si

Li

S

S

+

MOMO BDPSO

OMOM

CSA, THF

O S

83%

216

ð45Þ S

217

COOEt OH

Me3Si

Li

S

S

+

COOEt HCl, dioxane

S

91%

O

O

218

ð46Þ

S

219

A similar reaction was also involved in transformation of lactol 220 into a 2:1 mixture of the corresponding aldehydes 221 and 222 <1998EJO275> (Equation (47)). OH O S S 220

CHO

CHO PPTS 99%

+

S

S

O S 221

O S

ð47Þ

222 2:1

Intramolecular nitrone cycloaddition reaction of 223 led stereoselectively to a high yield of 224 <2002OL1227> (Equation (48)).

103

Functions Containing Three Chalcogens (and No Halogens) O S S O

H [3 + 2]

H Bn

N+

O S S OO

ð48Þ

N H Bn

O– 223

224

As reported earlier <1993TL2649>, bis-sulfonyl derivative 225 can be easily oxidized to give stereoselectively oxirane 226 (Equation (49)). Similarly, enantiomerically and diastereomerically pure spirocyclic bis-sulfinyl oxiranes 228 (R = Ph, substituted Ph, cyclohexyl) were prepared by stereoselective nucleophilic epoxidation of ketene thioacetal dioxides 227 (Equation (50)). These novel epoxides represent potentially versatile chiral substrates for the preparation of a variety of heterosubstituted carbonyl compounds <1998JOC7128, 2002OL1227>. In these cases, the nucleophilic peroxide attacks the top face of the ketene dithioacetal, whereas the cycloaddition reaction of nitrone mentioned above attacks the opposite face. SO2Me Ph

O2S

Me

MCPBA 87%

H

O SO2Me

Ph O2S

225

O S S O

226

O S S O

H2O2 or TBHP R

ð49Þ

Me

70–98 %

O

R +

H Major

H 227

O S S O

O

H

ð50Þ

R Minor 228

Hetero Diels–Alder reaction of ketene dithioacetal 229 with 3-(benzenesulfonyl)-3-butene-2-one gave 91% yield of 230 <1991JOC4098> (Equation (51)). Similarly, 1-oxo-(E,E)-2,4hexadienephosphonate with ketene dithioacetal 231 gave 232 <1995PS(103)259> (Equation (52)). PhSO2 S

S +

CCl4, 25 °C O

91%

229

PhSO2 S O

ð51Þ

S

230

O S

S

+

P(O)(OMe)2

S (MeO)2(O)P

231

ð52Þ

O S 232

Similar hetero [4+2]-cycloaddition reaction of 233 and silylketene dithioacetal 234 proceeds at room temperature to give dihydropyran 235 in good yield <2002JOC7303>. Similarly, 233 with alkyne 236 provided 85% yield of the 2:1 adduct 237 as the only isolated product <2002JOC7303> (Scheme 40). It has been established that the ketene dithioacetal group influences the stereospecificity of anodic carbon–carbon bond formation. Earlier similar enol ether enol–ether coupling led to 1:1 mixtures of stereoisomers <1992JA1033>. Anodic oxidation of 238 in the presence of THF led to good yields of one stereoisomer of 239 (Equation (53)). In the case of five-membered product, only the trans-isomer was formed. Alternatively, the six-membered product was established as the cis-isomer. No rational explanation of this fact has been found <2001OL1729>. Bridged bicyclic product 241 was obtained in 75% yield by the same method from 240 <2001T5183>

104

Functions Containing Three Chalcogens (and No Halogens)

86%

EtS

SiMe3

EtS

EtS

O P(OEt)2

O P(OEt)2

Me3Si

EtS

O

O

EtS

EtS 234 O P(OEt)2 CHO 233

235

SiMe3

SMe 236

O P(OEt)2

Me3Si

236 85%

MeS

O (EtO)2P

O

SiMe3

O

O P(OEt)2

O SMe 237

Scheme 40

(Equation (54)). The suggested mechanism includes anodic oxidation leading to the formation of a radical cation from the ketene dithioacetal, which in turn is trapped by the side-chain enol ether. Following trapping by MeOH, loss of a second electron, and a second trapping with MeOH, finally afford the cyclization products with one dithio-ortho-ester group and one acetal group. OMe OMe S

n

S

MeOH–THF 8 mA, 2.2 F/mol

n

70–94 % n = 1, 2

MeO

MeOH–THF 8 mA, 2.2 F/mol 75%

S

ð53Þ

S 239

238

MeO S

OMe S

S S

240

OMe MeO OMe

ð54Þ

241

Similarly, the reactions where the initial cation radical is trapped with oxygen nucleophiles were studied. For example, anodic oxidation of ketene dithioacetal 242 in methanol led stereoselectively to 243. This methodology was used also for the synthesis of more substituted compounds 243 and preliminary results of the synthesis of -lactones 244 were mentioned without any data concerning the stereoselectivity <2001OL1729, 2002JA10101> (Equations (55) and (56)). HO

n

S

MeOH 8 mA, 2.2 F/mol

n

OMe

O

70–94 %

S

S

ð55Þ

S n = 1, 2 242

R

243

R N

MeOH 8 mA, 2.2 F/mol

O

S

30–67 %

O

Me OMe

O S

S 244

S

ð56Þ

105

Functions Containing Three Chalcogens (and No Halogens) 6.03.5.2.5

Miscellaneous

Deprotonation of sulfonyl oxirane 245 with butyllithium followed by addition of S-phenyl benzenethiosulfonate gave 69% yield of 246 <1998JCS(P1)4097> (Equation (57)). PhO2S

i. BuLi, THF, –100 °C O PhO2S ii. PhSSO2Ph

O O

69%

O

O

PhS

ð57Þ

O

245

246

Nitroethene derivatives 247 undergo fast intramolecular cyclization in CF3SO3H to give dications 248, which in the presence of MeOH provided good-to-excellent yields of the corresponding products 249 <2001EJO1525> (Scheme 41). RS

NO2

HO + H N

TfOH

nS

+ S

HO SR

N

S

n

247

SR

MeOH

OMe

n

248

249

R = Me, PhCH2CH2; n = 1– 4

Scheme 41

Selective protection of the hydroxyl groups in 2,3-dithiothreitol 250 as t-butyldimethylsilyl ethers followed by treatment with trimethyl ortho-formate in the presence of camphorsulfonic acid (CSA) gave 80% yield of 2-methoxy-1,3-dithiolane 251 <1996JOC3611> (Equation (58)). SH i, ii

HO OH

TBDMSO

OMe S

80%

S

TBDMSO

HS 250

ð58Þ

251

i. TBDMSCl, imidazole, DMF; ii. HC(OMe)3, CSA, CH2Cl2

Methods for the Preparation of Functions R1C (OR2) (OR3)SeR4

6.03.5.3

No further advances have occurred in this area since the publication of COFGT (1995) <1995COFGT(6)67>.

6.03.6

MIXED SULFUR AND SELENIUM FUNCTIONS

6.03.6.1 6.03.6.1.1

Methods for the Preparation of Functions R1C(SR2) (SR3)SeR4 From dithioacetals

While tris(trifluoromethylsulfanyl)methylcyanide 66 was obtained in good yields by alkylation of 65 (cf. Section 6.03.3.1.5), the corresponding seleno analog 252 was obtained only in 7% yield <1994CB449> (Equation (59)). F3CS CN F3CS 65

i. NaH ii. CF3SeCl 7%

F3CS SeCF3 CN F3CS 252

ð59Þ

106

Functions Containing Three Chalcogens (and No Halogens)

Trans-2-methylseleno-1,3-dithiane 253 was prepared in 90% yield as a single isomer with the methylseleno group in equatorial position. The compound can be transformed to the cis-isomer 254 similarly as described for the 2-methylseleno-1,3-diselenane 184 <1996TL8015> (Scheme 42).

S S

i. BuLi ii. MeSeSeMe

i. LDA ii. MeOH

H S

90%

S

SeMe

93%

253

SeMe S S

H

254

Scheme 42

6.03.6.2

Methods for the Preparation of Functions R1C(SR2) (SeR3)SeR4

No further advances have occurred in this area since the publication of COFGT (1995) <1995COFGT(6)67>.

6.03.7

MIXED OXYGEN, SULFUR, AND SELENIUM FUNCTIONS

Chloroform solutions of vinyl selenides 255 in the presence of catalytic amount of CF3COOH quickly cyclized to the corresponding 2-butylsulfanyl-1,3-oxaselenolanes; the major isomers 256 were indicated by nuclear magnetic resonance (NMR) techniques <1997CL545> (Equation (60)). R

Se

OH SBu

R CF3CO2H 77–88%

Se

O

ð60Þ

SBu 256

255

A new convenient synthesis of dialkyldiselenides by photolysis of Barton PTOC esters 257 in the presence of 258 provided adducts 259. Though the adducts were not isolated but hydrolyzed in situ with hydrochloric acid and then oxidized with air to the required diselenides, the structure of 259 was firmly established by 1H-, 13C-, and 77Se-NMR <1996T11163> (Scheme 43).

Se N R1COO 257

+ S

R2

OR3

258

N S R3O R2 SeR1

R1SeSeR1 + R3COOR2 +

N H

S

259

Scheme 43

REFERENCES 1967AG(E)443 1969S17 1971TL2475 1972CB487 1972CB3280 1972HCA75 1973JA5829 1975CC216 1977S357 1977TL3549 1980JOC740 1980OPP229 1982JOC4750

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107

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108 1996JOC2877

Functions Containing Three Chalcogens (and No Halogens)

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Functions Containing Three Chalcogens (and No Halogens) 1999SC3841 1999SL1990 1999T4133 1999T10341 1999TL6423 2000AG(E)1089 2000CAR(329)879 2000JCS(P2)1777 2000JOC235 2000MI3149 2000MI3166 2000PJC1503 2000SL847 2000TL307 2000TL4185 2001CAR(330)409 2001EJO933 2001EJO1525 2001JA3369 2001JOC5822 2001M839 2001MI145 2001OL1729 2001OL2455 2001S1346 2001SM97 2001T555 2001T1289 2001T5183 2001TL8189 2002CAR(337)951 2002CAR(337)2399 2002CEJ1670 2002EJO2385 2002EJO3864 2002JA10101 2002JMAC2137 2002JOC7303 2002MI225 2002MI63 2002OL1227 2002S921 2002T3835 2002TL1377 2002TL6587 2003BMC357 2003CC776 2003MI36 2003TL7863

109

K. M. K. Kutterer, G. Just, Synth. Commun. 1999, 29, 3841–3853. J. Nishikido, F. Yamamoto, H. Nakajima, Y. Mikami, Y. Matsumoto, K. Mikami, Synlett 1999, 1990–1992. K. A. Tehrani, D. Borremans, N. De Kimpe, Tetrahedron 1999, 55, 4133–4152. A. Ishii, T. Nakaniwa, K. Umezawa, J. Nakayama, Tetrahedron 1999, 55, 10341–10350. S. Hiranuma, O. Kanie, C. H. Wong, Tetrahedron Lett. 1999, 40, 6423–6426. K. C. Nicolaou, H. J. Mitchell, K. C. Fylaktakidou, H. Suzuki, R. M. Rodriguez, Angew. Chem., Int. Ed. Engl. 2000, 39, 1089–1093. Z. Yang, W. Lin, B. Yu, Carbohydr. Res. 2000, 329, 879–884. G. P. Miller, I. Jeon, A. N. Faix, J. P. Jasinski, A. J. Athans, M. C. Tetreau, J. Chem. Soc., Perkin Trans. 2 2000, 1777–1780. A. Padwa, A. G. Waterson, J. Org. Chem. 2000, 65, 235–244. K. C. Nicolaou, H. J. Mitchell, R. M. Rodriguez, K. C. Fylaktakidou, H. Suzuki, S. R. Conley, Chemistry-Eur. J. 2000, 6, 3149–3165. K. C. Nicolaou, K. C. Fylaktakidou, H. J. Mitchell, F. L. Van Delft, R. M. Rodriguez, S. R. Conley, Z. Jin, Chemistry-Eur. J. 2000, 6, 3166–3185. G. Mlston, H. Heimgartner, Pol. J. Chem. 2000, 74, 1503–1532. A. G. M. Barrett, D. C. Braddock, D. Catterick, D. Chadwick, J. P. Henschke, R. M. McKinnell, Synlett 2000, 847–849. A. Lubineau, O. Gavard, J. Alais, D. Bonnaffe, Tetrahedron Lett. 2000, 41, 307–311. K. M. Sureshan, M. S. Shashidhar, Tetrahedron Lett. 2000, 41, 4185–4188. T. Praveen, M. S. Shashidhar, Carbohydr. Res. 2001, 330, 409–411. M. R. Bryce, A. S. Batsanov, T. Finn, T. K. Hansen, A. J. Moore, J. A. K. Howard, M. Kamenjicki, I. K. Lednev, S. A. Asher, Eur. J. Org. Chem. 2001, 933–940. J. M. Coustard, Eur. J. Org. Chem. 2001, 1525–1531. W. Yu, Z. Jin, J. Am. Chem. Soc. 2001, 123, 3369–3370. S. Knapp, G. J. Morriello, S. R. Nandan, T. J. Emge, G. A. Doss, R. T. Mosley, L. Chen, J. Org. Chem. 2001, 66, 5822–5831. W. Seebacher, E. Haslinger, R. Weis, Monatsh. Chem. 2001, 132, 839–847. U. Jordis, K. Bhattacharya, P. Y. Boamah, V. J. Lee, Molecules 2001, 7, 145–154. Y. Sun, B. Liu, J. Kao, D. A. d’Avignon, K. D. Moeller, Org. Lett. 2001, 3, 1729–1732. M. Dawid, G. Mloston, J. Warkentin, Org. Lett. 2001, 3, 2455–2456. K. Kurotobi, K. Takakura, T. Murafuji, Y. Sugihara, Synthesis 2001, 1346–1350. S. Frenzel, M. Baumgarten, K. Mullen, Synth. Met. 2001, 118, 97–103. M. Mella, M. Fagnoni, A. Albini, Tetrahedron 2001, 57, 555–561. H. N. Tran, T. N. Pham, Tetrahedron 2001, 57, 1289–1295. S. H. K. Reddy, K. Chiba, Y. Sun, K. D. Moeller, Tetrahedron 2001, 57, 5183–5197. F. Zouhiri, D. Desmaele, J. d’Angelo, M. Ourevitch, J. F. Mouscadet, H. Leh, M. Le Bret, Tetrahedron Lett. 2001, 42, 8189–8192. M. Karakawa, F. Nakatsubo, Carbohydr. Res. 2002, 337, 951–954. K. M. Sureshan, M. S. Shashidhar, T. Praveen, R. G. Gonnade, M. M. Bhadbhade, Carbohydr. Res. 29-11-2002, 337, 2399–2410. P. Wipf, Y. Uto, S. Yoshimura, Chemistry-Eur. J. 2002, 8, 1670–1681. D. Leinweber, M. Schnebel, R. Wartchow, H. G. Wey, H. Butenschon, Eur. J. Org. Chem. 2002, 00, 2385–2390. S. Sanchez, T. Bamhaoud, J. Prandi, Eur. J. Org. Chem. 2002, 00, 3864–3873. B. Liu, S. Duan, A. C. Sutterer, K. D. Moeller, J. Am. Chem. Soc. 2002, 124, 10101–10111. D. Kreher, M. Cariou, S. G. Liu, E. Levillain, J. Veciana, C. Rovira, A. Gorgues, P. Hudhomme, J. Mater. Chem. 2002, 12, 2137–2159. S. Arimori, R. Kouno, T. Okauchi, T. Minami, J. Org. Chem. 2002, 67, 7303–7308. A. Noomen, Progr. Org. Coatings 2002, 45, 225–230. M. S. Shashidhar, ARKIVOC 2002, 63–75. V. K. Aggarwal, S. J. Roseblade, J. K. Barrell, R. Alexander, Org. Lett. 2002, 4, 1227–1229. M. Clericuzio, I. Degani, S. Dughera, R. Fochi, Synthesis 2002, 921–927. A. G. M. Barrett, N. Bouloc, D. Christopher Braddock, D. Catterick, D. Chadwick, A. J. P. White, D. J. Williams, Tetrahedron 2002, 58, 3835–3840. Y. Zhu, D. G. Drueckhammer, Tetrahedron Lett. 2002, 43, 1377–1379. K. Kato, Y. Yamamoto, H. Akita, Tetrahedron Lett. 2002, 43, 6587–6590. C. Mugnaini, M. Botta, M. Coletta, F. Corelli, F. Focher, S. Marini, M. L. Renzulli, A. Verri, Bioorg. Med. Chem. 2003, 11, 357–366. M. Oba, N. Nishiyama, K. Nishiyama, Chem. Commun. (Cambridge) 2003, 776–777. M. Mergler, F. Dick, B. Sax, P. Weiler, T. Vorherr, J. Pept. Sci. 2003, 9, 36–46. M. Adinolfi, A. Iadonisi, A. Ravida, M. Schiattarella, Tetrahedron Lett. 2003, 44, 7863–7866.

110

Functions Containing Three Chalcogens (and No Halogens) Biographical sketch

Stanislav Ra´dl was born in Pilsen, Czechoslovakia. After graduation from the Prague Institute of Chemical Technology in 1976 he joined the Research Institute of Pharmacy and Biochemistry in Prague. He received his Ph.D. in medicinal chemistry in 1984. From 1985 to 2003 his positions included: research scientist, senior research scientist, project leader and department head. He spent 1992–1993 as a visiting scientist at the Hoffmann-La Roche Research Center, Nutley, NJ. Besides medicinal chemistry, his research interests include mainly synthetic aspects of various nitrogen-containing heterocycles. He has coauthored many original articles on antibacterial quinolones, as well as several reviews on various aspects of this group of therapeutic agents. Dr. Ra´dl has also written three chapters of Adv. Heterocycl. Chem. and one chapter of Comp. Heterocycl. Chem. 2nd edn. He is an editor of Collect. Czech. Chem. Commun. and contributing editor of Drugs of the Future.

Svatava Voltrova´ was born in Bohumı´ n, she studied at Prague Institute of Chemical Technology, where she obtained an M.Sc. in 1985 under the direction of Professor O. Cˇervinka and Ph.D. in 1989 under the supervision of Professor J. Kuthan. After spending 1991–1992 at the Dyson Perrins Laboratory, University of Oxford under the direction of Professor J. E. Baldwin, she returned to Prague and took up her present position as Assistant Professor at the Prague Institute of Chemical Technology. Her scientific interests include chemistry of heterocyclic compounds, especially aminopyridines, and amidiniumcarboxylates.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 75–110

6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen A. M. SHESTOPALOV N. D. Zelinsky Institute of Organic Chemistry, Moscow, Russia 6.04.1 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 15 ELEMENT 6.04.1.1 Functions Bearing Chalcogen and Nitrogen 6.04.1.1.1 Functions bearing oxygen and nitrogen 6.04.1.1.2 Functions bearing sulfur and nitrogen 6.04.1.1.3 Functions bearing selenium and nitrogen substituent 6.04.1.2 Functions Bearing Chalcogen and P, As, Sb, or Bi 6.04.1.2.1 Functions bearing oxygen and P, As, Sb, or Bi 6.04.1.2.2 Functions bearing sulfur and P, As, Sb, or Bi 6.04.1.2.3 Functions bearing selenium and phosphorus substituent 6.04.2 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLY A GROUP 15 ELEMENT 6.04.2.1 Functions Bearing Chalcogen and Boron 6.04.2.2 Functions Bearing Chalcogen and Silicon 6.04.2.2.1 Functions bearing oxygen and silicon 6.04.2.2.2 Functions bearing sulfur and silicon 6.04.2.2.3 Functions bearing selenium and silicon 6.04.2.3 Functions Bearing Chalcogen and Germanium 6.04.2.3.1 Functions bearing two oxygen and one germanium substituents 6.04.2.3.2 Functions bearing one oxygen, one sulfur, and one germanium substituents 6.04.3 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY A GROUP 15 ELEMENT OR A METALLOID 6.04.3.1 Functions Bearing Oxygen and a Metal 6.04.3.1.1 Functions bearing two oxygens and a metal 6.04.3.1.2 Functions bearing oxygen, silicon, and a metal 6.04.3.1.3 Functions bearing oxygen and two metals 6.04.3.2 Functions Bearing Sulfur and a Metal 6.04.3.2.1 Functions bearing sulfur, oxygen, and a metal 6.04.3.2.2 Functions bearing two sulfurs and a metal 6.04.3.2.3 Functions bearing sulfur, boron, and a metal 6.04.3.2.4 Functions bearing sulfur, silicon, and a metal 6.04.3.2.5 Functions bearing sulfur and two metals 6.04.3.3 Functions Bearing Selenium and a Metal

6.04.1

111 112 112 124 131 132 132 139 143 144 144 144 144 148 151 151 151 151 152 152 152 152 152 152 152 153 154 154 154 154

FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 15 ELEMENT

Compounds of this class were described previously in reviews <1969ZC201, B-1970MI001, 1971S16, 1977UK685, B-1979MI002, 1979T1675, 1985HOU(E5)3, 1995COFGT(6)103>. 111

112

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

6.04.1.1

Functions Bearing Chalcogen and Nitrogen

Functional groups bearing chalcogen and nitrogen are available by modification of precursors, which contain sp3- or sp2-carbon atoms, via cycloadditions or by other miscellaneous methods. This general order is adhered to throughout this section.

6.04.1.1.1

Functions bearing oxygen and nitrogen

(i) Functions bearing two oxygen and one nitrogen substituent The functional groups containing two ether groups and one nitrogen atom bonded to an sp3carbon atom are named acetalamides. They can be classified as acyclic acetalamides and cyclic acetalamides. This is a large class of organic compounds that is widely used in organic synthesis. (a) From sp3-carbon compounds. Ethyl orthoformate reacts with benzotriazole 1 to give (benzotriazol-1-yl)diethoxymethane 2 in 90% yield <1995H131> (Scheme 1). Diacetalamides such as 2 have been reported as convenient reagents for the syntheses of various organic compounds <1998CR409>. N

(EtO)3CH, performance fluid

N N

90% N

EtO 2

N N H

O

1

OEt, PF5080, ∆

O

OEt

N N

75%

N O

O

3

Scheme 1

A general method for the masked formylation by the electrophilic reagent, viz., 1-(1,3-dioxolanyl-2-yl)-1H-1,2,3-benzotriazole 3, has been reported <2000JOC1886>. Similarly to benzotriazole, imidazole 4 has been demonstrated to react with ethyl orthoformate to give diethylacetal 5, which was used for the synthesis of quaternized diethylacetal 6 (Scheme 2) <2002JAP2002105058>.

N

N

(EtO)3CH

N H 4

N + N

EtI, AcOEt

N EtO

OEt 5

EtO

Et I–

OEt 6

Scheme 2

Treatment of lactams such as 7 with CH(OEt)3 leads to the formation of N-diethoxymethylsubstituted derivatives such as 8 (Scheme 3) <1995S168, 1996S1196>. Similarly, ergoline-active analogs 10 were obtained from substituted indole derivatives 9 <1995AP609>. Building units 13 have been produced by the reaction of compounds 11 and 12. This reaction takes place in the presence of TsOH in 1,4-dioxane at 20 C (Equation (1)) <2002S274>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

113

CHOEt (EtO)3CH O

O

N H

N

7

EtO

OEt 8

R1

R2

N H

(EtO)3CH

R1

R2

R

R

N

OEt

EtO 9

10

Scheme 3

R2

R2 OH

EtO

+

R1

N

O

OEt

OH

R1

N O

12

11

O

ð1Þ

O 13 1

2

R = COOEt, CN, CHO, CH(CN)2; R = H, Br, I

A similar reaction has been used for the synthesis of indole derivatives <2000SL125, 2000JMC4563>. Pyrrolidone-2 and valerolactone diethoxyacetal 15 have been obtained in 60–70% yield by the treatment of compounds 14 with ethyl orthoformate (Equation (2)) <2002DOK61>. ( )n

(EtO)3CH, TsOH

( )n

O

N H

N EtO

O

ð2Þ

OEt 15

14 n = 1, 2

In the presence of MeONa or MeOLi in methanol, trichloropyrrole dimethylacetal 16 will react to give pyrrolidin-2-one 17. The reaction is driven to completion by the elimination of three chlorine atoms (Equation (3)) <2001TL4573>. Cl Cl O

N Bn 16

Cl

Me

MeONa or MeOLi, MeOH

OMe O

N OMe Bn

ð3Þ

17

Hydroxymethyldioxolanylfluorouracil 18 and other novel classes of 1,3-dioxolane nucleosides were synthesized by a coupling reaction. Thus, 2-methoxy-4[[(t-butyldiphenylsilyl)oxy]methyl]-1,3dioxolane or 2-methyl-1,3-dioxolane have been demonstrated to react with silylated 5-fluorouracil, thymine, cytosine, and 5-chlorocytosine in the presence of TMSOTf to give the corresponding 1,3-dioxolane nucleosides <1995JOC1546>.

114

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen O F

NH N

O OH O

O 18

A new type of Morinclaparvin A 20 has been obtained from 1,2-dihydroxyanthraquinone 19 (Equation (4)) <1995MI218>. R1

O

R1

O

R1

O

R1

O

OH

O

OH

ð4Þ

O NR2

19

20 R = H, Me; R1 = H, OH

Stereoselective electrophilic addition (bromo-pivaloyloxylation) to 1-[3,5-bis-O-(t-butyldimethylsilyl)-2-deoxy-D-erythro-pent-1-enofuranosyl]uracil has been used to produce 10 -C-branched uracil nucleosides such as 21 (R = O-Piv) and, when combined with nucleophilic substitution using organo-aluminum reagents, provides a new CC bond forming method at the anomeric position to give compounds such as 21 (R = CH2CH¼CH2) <1995MI417>. It was found that substituted pyrimidine nucleosides 22 exhibit a wide spectrum of biological activities, for instance they have been proposed as antitumor drugs <1995JAP07109289>. R1

O R2

NH N

NH

O

O

N R 5O

TBDMSO

O Br

O Br R

OR3 4

TBDMSO

R O 21

22

(b) From sp2-carbon compounds. Anilide 23 has been used for the synthesis of cyclic acetals. Primarily the oxygen in compound 23 was methylated on treatment with TfOMe to yield salt 24, which has been converted to diacetal 25 on further reaction with MeONa, which has been demonstrated to react with dimethyl-L-tartrate to give a mixture of atropoisomers of cyclic diacetal 26 (Scheme 4) <2001JA5130>. COOMe

MeOOC O

OMe N

Me

+

N But

23

O

Me But

TfOMe

O Me N

25

Scheme 4

N

Me But

But

MeONa MeOH

24

O

O

26

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

115

Ethylene 27 was converted into aziridine diacetal 28 on treatment with tosylazide at room temperature in acetonitrile. However, in this case acyclic compounds were also obtained along with aziridine 28 <2001T3909>. Similarly, the corresponding aziridines, containing RFSO2 group, were obtained from unsaturated compounds such as 27 on treatment with RFSO2N3 (Equation (5)) <2001T669>. Me

OTMS + TsN3

Me

Me

CH3CN, rt

OTMS

Me

OMe 27

N OMe Ts

ð5Þ

28

Azaadamantane diacetal 30 was synthesized using the traditional method by the reaction of azaadamantane 29 with propane-1,3-diol in benzene in the presence of TsOH (Equation (6)) <2001JCS(P2)522>. N

O

N

HO(CH2)3OH, TsOH, benzene, ∆, 48 h

Me

O O

Me Me

ð6Þ

Me

Me

Me 29

30

(c) Cycloaddition methods. The Vilsmeier reagents, generated from N,N-dimethylformamide and oxalylchloride, have been demonstrated to react with N-phenacylacetylanthranilic acid 31 to give compound 32, which contains the diacetalamino fragment as a part of the bicyclic system (Equation (7)) <1996T753>. O COOH N Ac

O Ph

Ph

N

O

O

31

ð7Þ

O O

32

1,3-Dipolar cycloaddition of nitrones such as 33 to dihydropyrrolediones such as 34 leads to the formation of diastereomers such as 35 and 36 (Equation (8)) <1996JCR(S)466>. Ar EtOOC ArCH=N-Ph

+ MeO

O

33

H

O N Ph

O

Ph N O N MeO Ph

34

O

Ar

O

H

O

+ Ph N O

O

35

N

ð8Þ

OMePh

36

The -diazocompounds 37 were transformed into isomu¨nchnone derivatives of (5(S))-phenyloxazin3-one and -2,3-dione (38 and 39), by treatment with aldehyde in the presence of rhodium(II) acetate (1 mol.%) with high diastereofacial selectivity and exo-selectivity though in comparatively moderate yields (Equation (9)) <1997TL4521>. OMe NO2

H O H Ph

N2 OH

N O

4-R-C6H4-CHO, O Rh2(OAc)4 (1 mol.%) O H CH2Cl2, rt Ph N O

X

37

X = C=O, CH2; R = NO2, OMe

O

HO O

or

Ph

H

H N

O OH

X exo-II 38

O 39

ð9Þ

116

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

Under Rh2(OAc)4 catalysis, substituted 2-amino-3-cyano-4,5-dihydrofurans will react with 3 equiv. of (PhCO)2C¼N¼N to give furo[2,3-b]pyrans 40 (Equation (10)) <1998JPR51>.

R1 3(PhCO)2C=N=N

R1 NC O

CN

+

Ph

R2

R2

O

O

NR2

Ph

O NR2

ð10Þ

40

The cycloaddition of 2-aza-1,3-dienes 41, which are readily available from carboxylic acids, gives 1,3-oxazinones 42 in good yields (Equation (11)) <1999TL7079, 2002S2043>. R1 OSi(CH3)2CMe3 R

1

R2

O +

i N CHOPr

R2CHO

HN

ð11Þ

O OPri

41

42

The Diels–Alder reaction of unsaturated compound 43 with azobutadiene 44 leads to the formation of tetrahydropyridine diacetal 45, which is the key compound in the synthesis of ent-Fredericamycin A (Equation (12)) <1995JA11839>. i. 25 °C, 20 h, CH2Cl2

EtOOC

EtOOC

ii. MeSO2Cl, Et3N +

EtO

OEt

N OH

43

EtO EtO

COOEt 44

N COOEt SO2Me

ð12Þ

45

Thermal hetero-[3+2]-cycloaddition of dipolar trimethylenemethanes (46 Ð 47), to N-acyl- or N-tosylimines 48 gives -methylene--pyrrolidone acetals 49 in high yields (Equation (13)) <1999CL879>.

N O

Heat

O

O

R2

O

R3

R1

48

O

δ R1

R2

δ

R1

46

N O R3

ð13Þ

49

47

Pyrrolidone acetal 53 has been obtained by the reaction of unsaturated isocyanate 52 and dimethoxycarbene 51, which was generated from oxadiazoline 50 <1996JA12848>. Besides, oxadiazoline 50 has been demonstrated to react with azide 54 to give the indole acetal 55, which was used in the synthesis of alkaloid ()-Tazettine (Scheme 5) <1998JA3664>. The reaction of piperidinecarboxylic acid 56 with carboxylic anhydrides afforded spiropiperidineoxazolines 57, which have been used in the synthesis of opioid agonists (Equation (14)) <1999SL1923>.

117

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

MeO N N

MeO

OMe

∆

O

MeO

OMe

NCO 52

OMe

O

N 51

50

MeO

OMe 53 O

THPO O

TO 50

O

O

+

O

O

OMe OMe

O N

O

CON3

O

MeO OMe

54

55

Scheme 5 R O PhHN

COOH

R

O O

Ph N

+ (RCO)2O N Bn

O

ð14Þ

N Bn

56

57

Nucleosides such as 58 undergo intramolecular cyclization by the action of [Pb(OAc)4/I2/h] or [(diacetoxyiodo)benzene (DIB)/I2/h] to give a mixture of anomers of spirouracil nucleosides such as 59 and 60, containing the diacetalamide fragment (Equation (15)) <1997TL6421>. O

O R1

N

O R4O

R5O

O

O

R4O

R4O

N

O

R2

R1 O

R R3O

R2

HN

HN

3O

R

R

R2

R1

O O

+

N R

3O

R O

59

O

ð15Þ

NH

60

58

Under base catalysis, O-glycosyltrichloroacetimidates 62, themselves obtained from protected glucose 61 and trichloroacetonitrile, undergo ring closure to give cyclic diacetals 63 (Scheme 6) <1994SL84>.

Y X RO

OR O OH 61

Y

CH2Cl2, CCl3CN, DBU OH

RO

OR O

X

HO O HN CCl3 62

Scheme 6

Y

OR O

X RO

O H2N 63

O CCl3

118

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

Tetrahydroquinoline diacetal 66 was synthesized by the reaction of compound 64 with unsaturated compound 65 (Equation (16)) <1999AG(E)1928>. Cl +

t

Bu O

OMe TBSO

NH

OMe

N

65

O

t

O

Bu O

64

ð16Þ

OTBS

66

Under the action of Bu3S4H and AlBN in toluene, oxazolines such as 67 undergo stereoselective reductive ring closure to give compounds 68 (Equation (17)) <2002TL6911>. SePh TBSO O

OTBS

O

Ph N

R

Ph

ð17Þ

R

N O

O 68

67

Spirocyclic diacetal 71, obtained via Scheme 7 from chiral compound 69, has been used in the synthesis of the rennin inhibitor SPP-100 <2000TL10091, 2001TL4819, 2002EUP1215201A2>. Other epoxides similar to diacetals 71 are available from oxazolyloxiranes <2002OL1551>.

Ph O Ph

i, ii

N

O Ph

78%

iii

N

N O

60%

OH

OH

O

Br 69

71

70

i. LDA, LiCl, THF, 0 °C; ii. allyl bromide, 0 °C; iii. NBS, DME-H2O, 0 °C

Scheme 7

The general method for synthesis of cyclic diacetals is exemplified by the transformation of compounds 72. Lactam acetals 73 were obtained by the isomerization of phthalimidomethyleneoxiranes 72 in the presence of Lewis acid. The reaction is driven to completion by the treatment of the reaction mixture with Et3N resulting in the formation of lactam diacetals in 73–96% yields (Equation (18)) <1997S1077, 1998CC43>. O

R2

i. Lewis acid, PhCl, 120–130 °C ii. Excess, Et3N

O N

O N O

R1 R2

O

R1

O

ð18Þ 73

72 O R1 =

,

,

,

;

R2 = N O

The reaction of -hydroxyiminonitriles 74 with 2 equiv. of resorcinol or phluoroglucinol 75 occurs in the presence of HCl and leads to the formation of benzofuro[2,3-b]benzofurans 76 containing the diacetalamino fragment (Equation (19)) <1999S751>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

119

R1

N

OH CN

OH +

74

R2

ð19Þ

2 R2

R1

R2

i. HCl, Et2O, 0 °C ii. NaOH aq. HO

OH

O

O NH2

OH

75 76

R2 = H or OH

(ii) Functions bearing one oxygen and two nitrogen substituents Functions bearing two nitrogen and one oxygen substituents are known commonly as ester aminals. The main methods for synthesis of ester aminals are described in COFGT (1995) <1995COFGT(6)103>, and almost no new publications in this area have appeared since. Oxazoloisoindole 79, containing the aminyl fragment, can be obtained in a mixture with phthalimide derivative 80 by the treatment of compound 77 with t-butyl-2-aminoacetate 78. In the same manner, compound 77 gives a mixture of oxazoloisoindol 82 and compound 83 on the reaction with chiral N1,N2,N2-trisubstituted-1,2-propanediamine 81 (Scheme 8) <1995JOC6987>.

O

O H2N N

N

OTf

O

COOBut +

H N

N

78 HN

O 77

O

But OOC ButOOC

COOBut

O 80

79 N

ButOOC

NH

COOBut

81 O N N But OOC

O N(COOBut)2

O +

N

COOBut N

O

N(COOBut)2 83

82

Scheme 8

(iii) Functions bearing one oxygen, one sulfur, and one nitrogen substituent Functional groups bearing oxygen, sulfur, and nitrogen are nonsymmetrical, and this reduces the number of synthetic routes available for their preparation compared to their symmetrical analogs. (a) From sp2-carbon compounds. Alkenes 85 were obtained from the aldehydes by condensation with [(4-methylphenyl)thio]nitromethane 84. The treatment of the electron-deficient alkenes 85 with lithium t-butyl peroxide in THF at 78 C according to a previously reported method <1990T7429> resulted in rapid epoxidation to give 2-(tolylthio)-2-nitrooxiranes 86 in good yields (Scheme 9) <1995JOC6431, 1999JCS(P1)937>. A ring-intact oxazoloisoindole derivative was obtained through the reaction of triflate 87 with an excess of benzylmercaptan producing equal amounts of diastereomers 88 and 89 in 86% yield and the ring-open product 90 in 9% yield (Scheme 10) <1995JOC6987>. Under SnCl4 catalysis, thiophenol has been demonstrated to react with 1,2-unsaturated nucleosides 91 in the presence of N-bromosuccinamide to give substituted nucleosides 92 (Equation (20)) <2002JOC6124>.

120

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen i, ii +

RCHO

TolS

iii

NO2

NO2

R

O R

STol

84

85

NO2 STol

86

i. But OK, ii. MeSO2Cl, Pr2i NEt, iii. ButOOLi

O

Me

Me

R = Ar,

,

Me

O

Me

O

OH O,

O

R

(R1 = Me, Pri, Ph)

1

OMe

Scheme 9 O

O OTf –

N

N

OTf O 87

O

BnSH Pr2i NEt

O

O

N

N

O N SBn

BnS

O

BnS

88

O

O

89

90

Scheme 10 O HN

O NH

O

N

RO

O

O

RO

N

ð20Þ

O

RO

SPh RO 91 92

The reaction of compound 93 with 94 gave cyanine dyes 95 (Equation (21)) <2002DP143>. Z I–

Cl

Z

N OH R

N R

N R

Z Me

+

i 94

93

Z I–

N O

Z = O, S, Se; R = (CH2)nCH3

ð21Þ

R Z N R

N R

i. pyridine, reflu x

n = 1, 4, 9

Z Me

95

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

121

(b) Cycloaddition methods. 1,2-Diaza-1,3-butadienes and 2-thiooxazolines or 2-thiothiazolines have been used in the synthesis of spiroheterocyclic compounds. At room temperature in THF, compounds 96 react with 2-thiooxazoline 97 to give spiroheterocycles (98, x = 0). Under the same conditions, adducts 100 can be accessed by the reaction of compounds 96 with 2-thiothiazoline 99. The subsequent ring closure of adducts 100 occurs on heating in THF or DMSO to give spiroheterocycles (98, x = 0) (Scheme 11) <2000SL1464>.

S S O R1O

N 96

THF, rt

99

R2

N

NH R1OOC

O

S

S

N H

H N

R O

N

O

S

i

NH

100

THF, rt

97

R1OOC S X

i. THF, ∆ ; or DMSO, 65–70 °C X = O, S

O N N H NH

R2

98

Scheme 11

2-Thiobenzooxazolines 101 and alkenes 102 on photolysis undergo [2+2]-cycloaddition to give the spiroadducts 103. In the case of compound 104, containing the vinyl fragment (R = CH¼CH2), photocyclization affords the tetracyclic compound 105 (Scheme 12) <2002HCA2383, 1999JCS(P1)1151>.

O S

+

R2

N OR

hν

R3

R1

R4

R4

N OR

102

O

R2 R3

R1 O

O

101

103 O S

hν

N

O S N

O

O

O

O 104

105

Scheme 12

Under Lewis catalysis by SnCl2 at 78 C, spirocompound 106 stereoselectively reacts with oxirane 107 to give compound 108. Under these conditions, the trans-dimethyl fragment of oxirane 107 undergoes inversion to the cis-dimethyl fragment (Equation (22)) <2000HCA3163>.

122

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen S

N

H

+

SnCl4, –78 °C

O

O

S O

Ph

S

N Ph

H

106

107

H H

S O

ð22Þ

108

Spiroheterocycles 111 are available from the reaction of phthaloyl chloride 109 with 1,5-bisnucleophiles 110 (Equation (23)) <1998CC1459>. O COCl

S +

COCl

R

Ph O R N

H N S

SEt 109

ð23Þ

O

R

110

111

(iv) Functions bearing one oxygen, one selenium, and one nitrogen substituent Sodium selenocyanate stereoselectively reacts with D-glucopyranose 112 to give cis-1,2-fused gluco-oxazolidine-2-selenone 113 as a single product. Also, gluco-oxazolidine-2-selenone 113 was obtained with high stereoselectivity from compounds 114 and 115 (Scheme 13) <2000CAL397>.

Ph

O

O

H O

Ph

O

O Ph

O

H

OHC Ph

KSeCN, AcNMe2

O O

O O

O

Ph

O

Ph

i. OsO4, Me-morpholineoxide, H2O, Me2CO

O

Ph

OH

114

112

Ph

Ph

OH O

S O

KSeCN, THF, AcNMe2

O

H H N Se

Ph

ii. KSeCN, THF, AcNMe2

Ph

Ph

O

O O

H

113

115

Scheme 13

Elemental selenium has been demonstrated to react with 1,2-dinitrobenzene 116 to give a mixture of benzoselenazole 117 and benzimidazole 118 on further reaction with carbon monoxide (Equation (24)) <1996KTK374>. NO2

i. Se, H2O, Et3N, THF

H N

N O

NO2 116

ii. CO

Se

O

+ N

41%

22%

117

118

ð24Þ

5-Alkylideneselenazolin-2-ones 120 were obtained by the reaction of 3-aminoalkynes 119 with elemental selenium and CO. Similarly, six-membered ring heterocycle 122 has been obtained from homopropargylamine 121 (Scheme 14).

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

123

O Se

Se, CO, DBU, THF

NHR

R1

R1

rt, 1.5 h

119

NR

120 O

Se (2 mmol.), CO (1 atm)

NHBu

CuI (2 mmol.)

Se

NBu

reflux

DBU, THF, rt

121

122

Scheme 14

Under the basic conditions, the reaction of alcohol 123 with elemental selenium leads to the formation of 1,3-oxazine-2-selenone in high yield 124 (Equation (25)) <1997PS335>. OH H 3C

Se, Et3N, THF NC

NH

80%

O

ð25Þ

Se

124

123

2-Oxoselenazolidine-4((R))carboxylic acid 127 has been reported as a stable seleno-containing physiologically active compounds. It was obtained in 40% yield from selenocysteine 126 and 1,10 -carbonylldiimidazole (CDI). Selenocysteine 126 was generated in the reaction mixture by the reduction of diselenide 125 with NaBH4 (Scheme 15). Se HOOC

Se

NH2 H2N

HSe

NaBH4

COOH

H2N

125

Se

CDI

O

COOH 126

N H

COOH

127

Scheme 15

Complex of LiAlHSeH has been widely used for the synthesis of different seleno-containing compounds, including synthesis of Se-methyl-N-phenylcarbamate 129. LiAlHSeH 128 has been obtained by the reaction of lithium aluminum hydride with black selenium powder (Equation (26)) <2001JA8408>.

LiAlHSeH

i. PhNCO ii. CH3I

O Ph

128

N H

SeCH3

ð26Þ

129

Selenocarboxylic acid was found to readily react with aryl-, acyl-, and arenesulfonyl isocyanates to give the acylcarbamoyl selenides 130 <2001HAC250>. O R1

O Se

NHR2

130 R1 = CH3, C4H9i , 1-Adamantyl, Ar R2 = C6H5, C6H4CO, 4-CH3C6H4SO2

2-Methylbenzselenazole was used for the synthesis of heptamethinecyanine dyes 131 <2002DP143>.

124

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

N R CH3 Se

Se O

Se

I– N R

N R 131 R = (CH2)nCH3 n = 1, 4, 9

10 --Phenylselenouridines (132 and 133) have been obtained by the reaction of 20 -ketouridine derivatives with PhSeCl in the presence of a base, or by addition of PhSeH to the corresponding nucleoside, containing unsaturated dihydrofuranic cycle <2000TL3643, 2001CEJ2332, 2002JOC6124, 2002JOC7706>. Phenylselenonucleosides (132 and 133) are potentially useful precursors for the synthesis of a variety of 10 -modified nucleosides. O

O NH

O

N

O

SePh

O TIPDS O

NH O

RO

O

N

O

SePh RO

O 133

132

TIPDS - 1,1,3,3-tetraizopropyldisiloxane-1,3-diyl

6.04.1.1.2

Functions bearing sulfur and nitrogen

(i) Functions bearing two sulfur and one nitrogen substituent(s) Literature examples of acetalthioamides synthesis are much rarer than those of acetalamides. However, the methods for synthesis of acetalthioamides and acetalamides resemble each other in many cases and sometimes are described in the same articles. (a) From sp3-carbon compounds. A complex of quinuclidine and BF3 134 has been deprotonated on treatment with BuLi/ButOK to give quinuclidine-2,2-diphenyl sulfide 136 in 52% yield on further reaction of the intermediate 135 with diphenyl disulfide (Scheme 16) <1999CC1927>.

BF3 Et2O N

BuLi, ButOK

(PhS)2 +

+

SPh

N – BF3

N M – BF3

N

134

135

136

SPh

Scheme 16

(b) From sp2-carbon compounds. 2-(Dimethylamino)-2H-1,3-dithiolene 138 has been obtained by the reduction of the 4-S-alkyl-1,3-dithiolium salt 137 with NaBH4 in EtOH. Compound 138 has been shown to be a useful precursor for the synthesis of tetrathiafulvalenes (Equation (27)) <1994JOC5877>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen EtOOC

S COOEt Me

137

S S

125

Me – PF6 N Me

NaBH4, EtOH EtOOC

S COOEt Me

ð27Þ

Me N Me S S

H

138

Dithialenes, containing the piperidine fragment, were obtained similarly <1997S407>. Bis(alkylthio)carbene has been demonstrated as a novel convenient reagent for organic synthesis <2000T10101>. Bis(alklylthio)carbene 140 was generated from oxadiazoline 139 on heating, similar to dimethoxycarbene 51 generated from 2,2-dimethoxyoxadiazoline 50. Further rapid reaction of bis(alklylthio)carbene 140 with isocyanate 52 leads to the formation of pyrrolin2-one tetrathioacetals 141 (Scheme 17).

RS N N

SR SR

SR Heat

RS

O

NCO 52

SR

N 140

RS

139

140 N3

O

O

SR 141

142

Scheme 17

Compounds 141 can also be accessed from acyl azides 142 and bis(alkylthio)carbene 140. By this methodology, various substituted pyrrolidines (143–148), including spirocondensed analogs, were obtained from the corresponding acylazides or isocyanates and bis(alkylthio)carbene <1999TL6891, 1999JOC1766>. PrS

SPr O SR

PrS

O

146

S

SPr O N SPr

SPr

PrS 145

PrS

N

N

PrS

O

Ph S

S

S

O

144

143

S

O

N

N RS

SPr SPr

Ph

S

O

O

O

SPr O N SPr

S

S

PrS

147

148

The formation of heterocycles 151 and 154 can be exemplified by the reactions of the in situ generated nitrilium phosphane ylide complex 149, which leads to either 1,2,3-thiazaphosphole 151 via [3+2]-cycloaddition or to sulfanyl-1,2-thiaphosphiran-3-amine 154 via an

126

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

intersystem-transylidation-type reaction giving the 1,3-dipolar complex 152 that undergoes ring closure to form intermediate 153 and subsequent decomplexation to give sulfanyl-1,2-thiaphosphiran-3-amine 154 as the final product (Scheme 18) <1999CC499>.

N [W] Ph

R N

CN

[W]

[W]

+

[W] PhC N P + R +

+ PhC N P R

–PhCN

149

S

[W]

+

P

R N

N C N P R

149

N Ph

150

N 151

+ PhCH2CS(CH3)2N)C=S

[W] R Me2N P S PhH2CS

Ph S

[W]

+

S P R

Me2N

–[W]

SCH2Ph

153

152

H P S

Me2N

154

[W] = W(CO)5

Scheme 18

A mixture of diastereomeric -lactams 157 is obtained by the reaction of thioketals 155 with the complex 156 (Equation (28)) <1994JOC7934>. O Ph

SMe +

R N

N

SMe

Ph SMe

N

ð28Þ

SMe

CO, 2 atm

(OC)5Cr

155

O

Et2O, hν

N

O

156

R

157

Under zirconium catalysis, compounds 158 undergo stereoselective assymetrical intramolecular [3+2]-cyclization to give hydrogenated pyrazolines containing the dithioacetal fragment 159 (Equation (29)) <2002JA13678>. R1

MeS

R2

NO2 Chiral Zn cat.

NO2

N HN S

R R

1

2

H H N HS

158

N S

ð29Þ

159

Under acid catalysis, compounds 160 undergo intramolecular ring closure to give hexahydropyrimidines containing a dithioacetal fragment 161 in 99% yield (Equation (30)) <1995TL6257>. S R2HN

O

O N H MeS 160

R1 SMe

R1

HN S

SMe N SMe R2

ð30Þ

161

Pyrrolidine dithioacetals 164 were obtained by the [3+2]-cycloaddition of ylides 162 to ethylenes 163 (Scheme 19) <1995TL9409, 1996TL711, 1996TL3915>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen R1 S S

+

N Me

CsF

SiMe3 Hal

–

S

+

S

N CH3

CH2

127

R1

R2 163

R2

S S N Me 164

162

Scheme 19

At room temperature, compounds 165 undergo intramolecular ring closure to give 1,2-dihydroazeto[2,1-b]quinazolines 166 (Equation (31)) <1997T13449, 2000JOC7512>. H SMe

R

N

N

SMe

C

Me

R

25 °C, 1 h

H N N

Ph

SMe SMe Me

ð31Þ

Ph

166

165

The cycloaddition of dithioesters 167 to acids 168 using triphosgene as an activator gave 4,4-bismethylsulfanylazetidin-2-ones 169 in good yields (Equation (32)) <2002T2215>. MeS

Et3N, triphosgene, 0 °C, 12 h N R1 + R 2

COOH

MeS

O

58–68% 167

R2

168

SMe SMe N 1 R

ð32Þ

169

R1 = Ph, CH2Ph, CH2COOMe, CH(Me)COOMe; R2 = OMe, OPh

(ii) Functions bearing one sulfur and two nitrogen substituents (a) From sp3-carbon compounds. Tris(azolyl) methylthiolates 170 have been obtained by the reaction of the corresponding trimethylsilylazoles with [CF3S(NMe2)2]+[CF3S] <2001AG(E)1247>. –

X

N C S N

+

CF3S(NMe2)2

3

170 X = CH, N

Pyrimidine 171 reacts with benzyl bromide to give benzyl-substituted imidazo[1,5-a]-1,3,5triazine 172. The reaction proceeds via intramolecular ring closure at the sulfur atom and leads to the formation of the imidazole ring <1995JMC3558>. Compound 172 is also accessible by the reaction of imidazotriazine 173 with benzyl bromide (Scheme 20). Similarly, S-alkylquinazoline is obtained from benzopyrimidinethione and -dimethylamino-1chloroethane in the presence of a base <2002MI335>. (b) From sp2-carbon compounds. Nitration of compounds 174 and 175 with 55% HNO3 yielded 2,2,4-trinitro-3-chloro-3-thiolene-1,1-dioxide 176 but its yield did not exceed 8% (Scheme 21) <2002MI1111>. 2-Hydrazino-2,3-dihydrobenzothiazoline 177 is widely used for the syntheses of heterocycles, azomethines, and other compounds containing the benzothiazoline fragment (178–182). This compound reacts in the same way as monosubstituted hydrazines (Scheme 22) <1999MI325, 2001MI129>.

128

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

S

N

i. Me3SiCl, (Me3Si)2NH, Py ii. K2CO3, MeOH

NH2 Me

HN O

Br

NHCHO

O

Me

171

HN

N

S

N

N Me

O HN S

N

Me

K2CO3, MeOH

N

N H

172

Me 173

Scheme 20

Cl

Cl

NO2 55% HNO3 O

S

NO2

Cl

O2N

O

NO2

55% HNO3

O2N

HON

S O

O

176

174

S O

O

175

Scheme 21

Me N

Me N

H HO N N

NH S

H N C

178

Me N

OH

S Ar

HO

179

i

O

N S

O

H N

S

OH

H2N iii

180

Me N NHNH2 S 177 i, iv

ii

Ar

Me N

N

S

NHNHCH2NH S

N Me 182

N 181 N

i. ArCHO, AcOH, EtOH; ii. N iii. CH2(CN)COOEt, EtO, K2CO3;

, HCHO, HCl, H2O; NH2

iv. HSCH2COOH, Dioxan

Scheme 22

S N N H O

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

129

Similar to 2-hydrazino-2,3-dihydrobenzothiazoline 177, imidazothiazoline hydrazide 183 has also been demonstrated to react with aromatic aldehydes to give substituted hydrazones <2002UKZ46>.

NHNH2

N S

N H

O

183

5-Aminothiadiazolines 184 were obtained by the reaction of substituted thiosemicarbazide with tetracyanoethylene (Equation (33)) <1998PS141>.

S RNHCNHNH2

+

NC

CN

NC

CN

N N

EtOAc 20–23%

RHN

S

CN

ð33Þ

CN

184

Heterocycles 186 and 187 have been obtained from dithiosemicarbazide 185, which was produced by the reaction of 1,4-dichlorophthalazine with thiosemicarbazide. Besides, compounds 186 and 187 can be accessed directly from 1,4-dichlorophthalazine and thiosemicarbazide in one step without isolation of compound 185 (Scheme 23) <2001IJC(B)500>.

O

S S N N C NH2 H NH N NHNHC NH2 S

S

N

CS2

NH N N

KOH, EtOH N

S

NH

S

N

S

N

NAOH, H2O N

N S

186

N

ClCH2COOH

HN

185

S N

HN

S

O 187

Scheme 23

The intramolecular 1,3-dipolar cycloaddition of the o-allenylaryl fragment to the betaine fragment of thienopyrimidine 188 occurs on heating and affords framework compounds 189. Similarly, the intermolecular cycloaddition of maleineamide to thienopyrimidines 190 leads to the formation of adducts 191 containing the bridging sulfur atom (Scheme 24) <1997JOC3109>. 3,3,6,6-Tetramethyl-1-thia-4-cycloheptane 192 reacts with isothiocyanates 193 in a ratio of 1:3 on heating in an autoclave without solvent to form adducts 194 in 17–60% yield. The formation of the compound 194 can most plausibly be explained by a concerted [3+2]-cycloaddition (Scheme 25) <2000JOC8940>. The highly reactive 4-phenyl-1,2,4-thiazoline-3,5-dione 195 has been demonstrated to interact with 4-phenyl-1,2,4-triazoline-3,5-dione 196 as a dipolarophile to give cycloadducts 197 in excellent yields (Equation (34)) <1995T6651>.

130

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

( )n R1OOC Me

–

O

+

N N PG

S

Deprotection

R

Me

188

Ph R1OOC Me

O

–

O

+

N N Me

S

63%

Me

O

190

O

N N H 189

S

Ph

O

R1OOC

Toluene, ∆

N Me

+ Ph

( )n

R1OOC

∆

N

R

Ph H

S

N Me H O

O N Me

191

PG = protecting group, n = 1, 2

Scheme 24

+

S

R

N C S

120 °C

R S C N

S S N

17–60%

R 192

193

+

S

R S C N

S

S

–

N R

S S S

N R

R N

N N R R

S

194

R = Me, Ph

Scheme 25

O Me

S Me Me

N N

+ N ( )n 195

O

O

N Ph 196

Ph O O

Me O O S N

N N

Me

N

( )n

ð34Þ 197

n = 1, 2

The reaction of 1,2-diaza-1,3-butadienes 198 with 2-thiooxazoline 199 in THF at 20 C leads to the formation of the spiroheterocycle 200 containing the CNNS-fragment (Equation (35)) <2000SL1464>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

131

O O R1O

N

R2

N

S

+ N H

O 198

HN H R2 N N

THF, 20 °C

O

ð35Þ

S O

R1OOC

200

199

(iii) Functions bearing one selenium, one sulfur, and one nitrogen substituent (a) From sp2-carbon compounds. N-Methylbenzoselenazole-2-thiones such as 201 have been alkylated at the exocyclic sulfur atom by the strong alkylating agents such as diethoxycarbonium tetrafluoroborate, which was generated in situ from BF3Et2O and triethylorthoformate, to afford compounds such as 202 on further electrochemical reaction (Equation (36)) <2002JCS(P1)1568, 2000MI92>. Me N S

Me Electrochem N S + Et Se

CH(OEt)3, BF3·Et2O reflux

Se

S Et

Se

BF4–

201

6.04.1.1.3

Me N

ð36Þ

202

Functions bearing selenium and nitrogen substituent

The salt 203 obtained via Scheme 26 has been used for the synthesis of methyltetraselenafulvalene <2001MI1035>.

13

C-labeled tetra-

Cl NH

580–600 °C

Se O N

Se *CSe2

*CH2Cl2 + 2Se

i. H2SO4 ii. HPF6

* Se

N

+

N

Se * Se

* Se

PF6–

O

+

H 2N

i. H2Se, EtOH ii. (EtO)3P/ toluene

Se * Se

Se * Se

203

Scheme 26

Spiroselenoamide 205 has been obtained in a mixture with compound 206 by the treatment of compound 204 with AgBF4 (Equation (37)) <2001CC1336>. Me N Se

204

Se N Me

AgBF4, toluene, ∆

Me N Se

Me N +

Se N Me 205

+

Se +

Se

206

N Me

·2BF4–

ð37Þ

132

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

6.04.1.2

Functions Bearing Chalcogen and P, As, Sb, or Bi

6.04.1.2.1

Functions bearing oxygen and P, As, Sb, or Bi

(i) Functions bearing two oxygen and one phosphorus substituent 1,1-Diethoxyethylphosphinates and phosphonites have been demonstrated to be convenient reagents for the synthesis of different functionally substituted phosphoric acids and phosphinates. Some reactions of the synthons (207–209) are outlined below (Table 1). Final ketal-protected phosphorus acids can be deprotonated on further treatment with 1–2 equiv. of trimethylsilylchloride in CH2Cl2, containing up to 5% weight of ethanol, and stirring of the reaction mixture for several hours under argon at room temperature <1995TL9385>.

R O (EtO)2C PH OEt

R OSiMe3 (EtO)2C P OEt

R O (EtO)2C P Me OEt

207

208

209

R = H, Me

Table 1 Synthesis of functional phosphorus acids Reactant

Condition

Bn N Bn

N

N

Toluene 100 C, 1 h, 60% Bn

Product O Me Bn-NH-CH2 P OEt OEt OEt

Na, toluene 5–20 C, 3 h, 80%

Na, toluene 0–20 C, 3 h, 60%

NH Cl

EtOOC

THF 60 C, 3 h, 95%

O P H OEt

NH Cl

Cl

O Me P OEt OEt OEt

EtOOC

O Me P OEt OEt OEt

NO2 H2N

i. BuLi, THF, 78!0 C, 1 h, 60% ii. Ni.H2, EtOH, rt, 90% Cl Cl

O P H OEt

O Me P OEt OEt OEt

CH2Cl

Cl

O Bn-NH-CH2 P H OEt

O Me P OEt OEt OEt

Br

Deprotected product

NH Cl

Cl

O P H OEt

EtOOC

O P H OEt

H2N

Cl

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

133

1,3-Dioxalanes 210 have been phosphorylated by treatment with diethyl chlorophosphite. The reaction proceeds through oxidation of the phosphorus atom (PIII ! PV) in the presence of an orthoester and carboxylic acids to give a mixture of exo- and endo-isomers of nucleosides 211 and 212 (Equation (38)) <1996TL3497>. TBDPSO

O B

TBDPSO

O B

TBDPSO

(EtO)2PCl, CH3CN O R

O B

+

O

O

OEt

O

R

O

P(O)(OEt)2

(EtO)2(O)P

ð38Þ

R

endo-isomer

exo-isomer

210

O

211

212

R = H, Me, Ph; B = T, U, CBz, GBz, ABz

Alkylation of the hypophosphorus acid derivative 213 with 4-iodobenzyl bromide has been used to obtain compound 214, which was used in the synthesis of aminocarboxylic acid 215 (Scheme 27) <2000BMCL2343>.

Br, i O P H OEt

EtO EtO

EtO EtO

I

O

O OEt P OEt OEt

ii, iii

P OEt

213

I

214

R1HN

R1 = Boc, Z; R2 = Me, Bn

COOR2 215

i. NaH, THF, –10 °C to rt; ii. BOC-iodoAla-OMe, Zn, BrCH2Br, TMSCl; iii. (2-furyl)3P, Pd2dba3, DMA–THF, 60 °C

Scheme 27

The phosphorylated analog of sialic acid was obtained from N-acetyl--D-mannosamine 216. Initially compound 216 has been phosphorylated by dimethyl[1-(bromomethyl)ethyl]phosphonate 217 in the presence of indium to give the threo product 218, which undergoes subsequent ozonolysis to give - and -sialoside acid mixture in a ratio of 5:1 (Scheme 28) <1996JOC9538>. O

OMe P

HO HO HO

NHAc O + OH Br O 216

O P OMe OMe

OMe

CH2 OH

i 81%

217

ii, iii 90%

AcHN HO

OH OH

HO

AcHN

OH OH OH 218

OH

O P OMe HO MeO O

219

i. In, EtOH, H2O, 6 days; ii. O3, MeOH, –78 °C; iii. Me2S, MeOH, –78 °C to rt

Scheme 28

Dialkoxymethyl(diphenyl)phosphine oxides 220 and aldehydes 221 undergo the Horner–Wittig reaction to give asymmetrical -hydroxy carboxylic esters 224. The reaction proceeds through intermediates 222 and 223 (Scheme 29) <1999MI2270>.

134

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen RO OR

O OR R1 O Ph P + H Ph OR 220

R1

221

Ph ROK or ROLi R1 P Ph H OH O 222

OR

AD

OR

71–92%

R1 * COOR OH

223

224

AD-mix α[(DHQ)2PHAL] config. (S ) AD-mix β[(DHQ)2PHAL] config. (R )

Scheme 29

Synthesis of the 50 -homologated H-phosphinate 228 was achieved as follows. The 50 -homologated phosphinate 225 was made available from boron trifluoride-catalyzed oxetane ring opening with a phosphinate-stabilized carbanion. Subsequent hydrolysis of the 30 -benzoate followed by silylation yielded 226. Selective removal of the orthoester protecting group from 226 liberated the ethylH-phosphinate 227. Hydrolysis with triethylamine, water, and ethanol produced the corresponding H-phosphinic acid, which was re-esterified with allyl alcohol, using DCC as the condensing agent, to produce the allyl-H-phosphinate 228 (Scheme 30) <2001SL467>.

O O

+

T

EtO Me EtO

O P Me OEt

EtO Me EtO

O P

i, ii

EtO BzO

O

T

225 EtO Me EtO

O H P

O P iii

EtO

TBDPSO

O

O H P iv, v

EtO TBDPSO

T

226

O

O TBDPSO

T

227

O

T

228

i. NaOMe, MeOH, rt, 85%; ii. TBDPS-Cl, imidazole, DMF, rt, 91%; iii. Me3SiCl, EtOH, CHCl3, rt, 71%; iv. Et3N, EtOH, H2O, rt, 95–98%; v. allyl alcohol, DCC, 2 mol.% DMAP, THF, rt, 69–73%

Scheme 30

Compound 229 has been used for the synthesis of inhibitors of the bacterial cell-wall biosynthesis enzyme MurC <2001BMCL1451>. Hypophosphorus acid synthons 230 were used for the synthesis of phosphorylated oligonucleotides <1995SL703, 1998SL283>, carbohydrates <2001SL473>, and other organic compounds <1999SL1633, 2002SL525>.

EtO EtO

R2 O P H R1O OR1

O O S O P O OEt

R1O

229 1

R = Me, Et, Ph;

230 R2

= H, CH3

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

135

(ii) Functions bearing one oxygen and two phosphorus substituents Tris(trimethylsilyl)phosphite 232 reacts with acyl halides 231 to produce 1-hydroxymethylene1,1-bisphosphonic acids 233 on subsequent hydrolysis of the intermediates (Equation (39)) <2001PIAWO0109146, 2001TL8475>. i. THF, 25 °C ii. MeOH, 25 °C, 1 h

O R

Cl 231

OH O OH R P OH O P HO OH

+ n-P(OSiMe3)3 61–98% 232

ð39Þ

233 R = Me, C5H11, C11H23, Ph, PhCH2, 4-MeOPh, 4-NO2Ph, 3-Py n = 2–6

A one-pot synthesis of methyl(benzyl)hydroxylbisphosphonic esters was achieved without a protic reagent which removes the unusual -ketophosphonate step. Thus, reaction of P(OCH2Ph)3 with RCOCl (R = Me, Ph, Bu, CH2OMe) in MeOH or AcOH gave (PhOCH2)2P(O)C(R)(OH)P(O) (OCH2Ph)2 <1996PS295>. Synthesis of compounds 234 (R1 = H, NO2, halo, amino, C1–6-alkyl, C1–6-alkoxy, aryl, heteroaryl; 2 R = H, halo, amino, C1–6-alkyl, C1–6-alkoxy, aryl, heteroaryl; Y = O, S, NH, etc.; Z = C1–5-alkylene, aminoalkylene, m, n = 0–1) has been reported <2002GEP10114352>. Thus, chlorination of 4-RC6H4CH2CH2CH2COOH with oxalylchloride followed by treatment with P(OSiMe3)3 produced 4-RC6H4CH2CH2CH2C(OSiMe3)[P(O)(OSiMe3)2]2. Hydrolysis of the latter followed by treatment with NaOAc afforded 4-RC6H4CH2CH2CH2C(OH)[P(O)(ONa)(OH)][P(O)(OH)2] (R = N(CH2CH2Cl)2).

R1 Yn Zm R2

PO3H2 OH PO3H2

234

Every so often, directly carboxylic and aminocarboxylic acids can be used for synthesis of 1-hydroxy-1,1-diphosphorus compounds instead of acyl halides. In these cases PCl3, POCl3, and PCl5 can act as chlorination agents and H3PO4 as a reagent for phosphorylation <2002PIAWO0290367, 2002JMC2185, 2000USP6143923, 2000JAP281690, 2003USP3013918, 2001MIP2173321, 2002MIP2178793, 1998BRP2316945, 1998PIAWO9834940, 1998GEP(O)19737923, 1997PIAWO9739004, 1995JOC8310>. A typical example of such reaction is presented below (Equation (40)).

H2N

COOH

i. H3PO3 ii. PCl3 iii. H2O

O HO

57%

OH P

OH P OH O OH

ð40Þ

H2N

A method of synthesis of radioiodinated aminobisphosphonates 235 (X = 125I, 211At; Y = CH, N) has been described with active esters N-succinimidyl-3-(trimethylstannyl)benzoate and N-succinimidyl-5-(trimethylstannyl)3-pyridinecarboxylate as precursors. The isolated and purified radiolabeled intermediates were coupled to give 3-amino-1-hydroxypropylidene1,1-bisphosphonate [H2NCH2CH2C(PO3HNa)2OH] in high yields ranging from 60% to 97% <1999MI397>.

136

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen O

HO ONa HO P O

RO O RO P

P O HO ONa

RO P O RO

N H

Y

Y

235

O

236 R = Me, Et, iPr

1-Hydroxybisphosphonates [(R1O)2P(O)]2C(OH)R3 (R1, R2 = H, straight or branched C1–6 alkyl, benzyl, aryl, Na, Ca, Li, K; R3 = C1–10 straight chain or branched alkyl, Ph, benzyl, aryl, amido, organothio, alkoxy) and substituted hydroxybisphosphonates were obtained by the reaction of anions of dialkyl phosphites with acid halides. It is preferred that this reaction takes place at a low temperature in the presence of a base so that rearrangement to dialkyl(dialkoxyphosphinyl)phosphates is minimized. Thus, KN(SiMe3)2-mediated reaction of (EtO)2P(O)H with hydrocinnamoyl chloride produced 60% of [(EtO)2P(O)]2C(OH)CH2CH2Ph along with 9% of [(EtO)2P(O)]2CHCH2CH2Ph, and 3% of ester <1996PIAWO9633199>. The feasibility of synthesizing -hydroxy -alkyl-/aryl methylenebisphosphonates via Grignard addition to tetraalkyl carbonylbisphosphonates was shown; and some current and potential therapeutic uses of bisphosphonates and phosphonocarboxylates were summarized <1999PS313>. Synthesis of acylaminoalkanediphosphonates 239 with 41–87% yields was achieved by the reaction of acyl halides 237 with aminoalkyldiphosphonates 238 <2002MIP1333210>. It was shown that mono-, di-, and trisodium salts of compounds 239 can be obtained depending upon the pH of the media (Equation (41)). O Cl

+

HO ( )n

R

O OH P OH P OH

i. NaOH, H2O ii. HCl, H2O

( )n

O OH P OH P OH

NH

O OH

HO

NH2 O OH 237

ð41Þ

O

238

R 239

n = 2, 3, 5

1-Hydroxyethylidene-1,1-bisphosphonic esters 240 were used as a precursor for selective synthesis of mono- or disalts of these esters (241 and 242) (Scheme 31). <2000S633>.

HO Me

O OR P OR P OR O OK 241

KI

HO

R = Me, Et

Me

O OR P OR P OR O OR 240

NaI

HO

R = Me

Me

O OR P ONa P OR O ONa 242

Scheme 31

Arylcarbonylphosphonates 243 react with 2-isocyanato-4H-1,3,2-benzodioxaphosphorin-4-one 244 to give bicyclic aryl bisphosphonates 247. Probably, this reaction proceeds through intermediates 245 and 246 (Scheme 32) <2002MI980>. 1,2-Dihydro-1,3-diphosphinine 248 and mesitylnitrileoxide 249 undergo chemo-, regio-, and stereoselective 1,3-dipolar cycloaddition to give cyclic allene 250 (Equation (42)) <2000AG(E)1261>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen O Ar

O

OR P OR O

+

P O

Benzene, 80 °C NCO 8 h, argon

O

O 243 O

O

Ar

OR P OR O

Ar O

–

N O + P O

NCO O–

+

P O

O 245

244

O O P N

O

OR P OR Ar O

60–70%

137

P O

OR OR

O

O 247

246 R = Me, Et; Ar = 4-ClPh, 1-naphthyl

Scheme 32

But P

But

But

P

But

C N O Me

Me

But

+

P

77%

But

P

But O N

Me

ð42Þ

But

Me

Me 249

248

Me

250

(iii) Functions bearing one oxygen, one nitrogen, and one phosphorus substituent Synthesis of the compound 253 was achieved by the reaction of diisopropylammonium salt 251 with bis(diisopropylamino)(trimethylstannyl)phosphine 252 in the presence of MeONa in methylene chloride (Equation (43)) <1998EJI1539>.

+

– (Pri)2N=CHClPO2Cl2

+

SnMe3 P N(Pri)2 N(Pri)2

i. CH2Cl2 ii. THF, MeONa

MeO (Pri) 2N

90%

252

251

P

N(Pri)2 N(Pri)2

ð43Þ

253

[3+2]-Cycloaddition of diazoketones 254 to compounds 255 leads to the formation of 5-alkylidene-4,5-dihydro-3H-1,2,4-diazaphospholes 256 (Equation (44)) <1996T10053>.

(Pri)3Si

O C C Bui N2 254

+

O SiMe3 X Bui P 255

But 81–83%

Me3SiO

N N P X

O Si(Pri)3 But

ð44Þ

256

X = Cl, SiMe3

Atimicine A undergoes selective phosphorylation along formylamino group with hydrophosphoryl compounds 258. The reaction is driven to completion by the elimination of the formyl group resulting in the formation of compounds 259 containing NHCH(OH)P fragment (Equation (45)) <1996KFZ31>.

138

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen Prn

Prn O O Me(H2C)5

Me O O

O

Me

O

O

O O O MeOH H P OR Me(H2C)5 58–81% OR 258 O NHCHO

+

N H

Me O O Me

O

O OH

N H OH

OH

N H

OR P OR O

ð45Þ

259

257 R = Et, Ph, H

Phosphorylated oxazoloisoindole 262 has been obtained by the reaction of phthalimide 260 with diethylphosphonate 261 (Scheme 33) <2000PS107>.

O

O Br

N

O + H P OEt OEt

O

i, ii, iii N 86% O P O EtO OEt

261

260

262 NH2

iv, v, vi N

OH

Pri

93%

Pri

O P O Ph Ph

263

264 i. NaTHF; ii. THF; iii. NH4Cl, H2O; iv. Phthalic anhydride, xylene; v. TsCl, CH2Cl2, Py; vi. Ph 2PH, KH, THF

Scheme 33

Similar phosphorylated oxazoloisoindole 264 can be accessed by the enantioselective reaction of aminoalcohol 263, phthalic anhydride, and Ph2PH <2001TA923>.

(iv) Functions bearing one oxygen, one sulfur, and one phosphorus substituent Derivative of pulegone 265 gives compound 266, containing oxygen, sulfur, and phosphorus at an sp3-carbon atom, on the chain of subsequent reactions with BuLi, ClPPh2, and BH3SMe2 <2000JA10242>. Reaction occurs stereoselectively with retention of configuration of the starting reagent 265 (Equation (46)).

i. BusLi, –78 °C ii. ClPPh2, –78 °C to rt iii. BH3·SMe2

Me

O Me Me

S

265

81%

Me

O Me Me

S 266

Ph P Ph BH3

ð46Þ

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 6.04.1.2.2

139

Functions bearing sulfur and P, As, Sb, or Bi

(i) Functions bearing two sulfur and one phosphorus substituent The reaction of complex 267 with ylides 268 or with phosphine R3P and carbon disulfide yielded the salt 269, which was acylated with acetyl chloride to produce tributylphosphonium salt 270 (Scheme 34) <1996JOC9585>. S R3P 268

S Me

[Cp2ZrHCl]n

i. CS2; ii. R3P

267

R3P

S

H

S

+

ZrCp2Cl

S

Bu3P S

O O

Cl

–

Me

269 270

R = Me, Bu.

Scheme 34

Dithioacetal formylphosphonates 273 have been obtained by the reaction of disulfides 272 with -phosphorylcarbenes, generated from the corresponding diazocompounds 271 <1996S1232>. Cyclic dithioformylphosphonates 274 and 275 were made available by the introduction of the cyclic disulfides in this reaction (Equation (47)). O (R1O)

2PCHN2

+

R-S-S-R

BF3·Et2O, CH2Cl2, 25 °C

O SR R1O P OR1 SR

4–93% 272

271

ð47Þ

273

R1 = Me, Et; R = Me, Et, Pr, Ph, 4-MePh, COOEt

O MeO P

S

OMe

O MeO P

S

S S

S

S

OMe

274

275

General methods for the synthesis of optically active -phosphoryl sulfoxides 277 have been reported. Compounds 276 have been subjected to lithiation and methylsulfonation with MeSO2SMe at P- and S-linked carbon atom to give -phosphoryl sulfoxides 277 (Equation (48)) <1997T2959>.

O R1O

P R1O

S O

R2

i. BunLi ii. MeS(O)2SMe

SMe

O R1O

P R1O

S O

R2

ð48Þ

277

276 R1 = Me, Et; R2 = Me, Ph, 4-MePh

Phosphonate bisdisulfoxide 278 can be accessed by the recently developed method. This reagent can be used for asymmetric synthesis of -aminoamides <1998JOC7128, 1999PS337>. Compound 278 was obtained as shown in Scheme 35.

140

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen i. Chlorosuccinimide ii. P(OEt)3 S

S

[O] S

S

O

43–58%

S

S

O

O P OEt OEt

O P OEt OEt

278

Scheme 35

Compounds 280 and 281 were obtained in high yields by hetero-Diels–Alder reaction of phosphonodithioformate 279 with cyclic dienes <2000TL7327> (Scheme 36).

Cyclopentadiene

S OPri P MeS O

OPr

CH2Cl2

i

O S PriO P C SMe OPri

Me

CH2:CMeCMe:CH2,

S OPri

THF

Me

P MeS

279

280

OPri

O

281

Scheme 36

Phosphorylated crown ethers 286 have been obtained by the reaction of compounds 282–285 and triethoxyphosphine. Ethers 286 are convenient reagents for the synthesis of crown ethers of tetrathiofulvalenes (Scheme 37) <2001EJO933>.

O S

S

S

S

O O

S

S

S

S

O

S O O

75%

282

i, ii, iii

O (OEt)2P

iii

O O

75%

285

O S

S

H S

S

CF3SO3–

O O O 286

ii, iii

O S

S

75%

75%

ii, iii

O

MeS

O S

S

S

S

O

MeS S

S

O

O

O

O

283

284 i. CF3SO3Me, CH2Cl2, EtOH; ii. CF3SO2H, MeCN; iii. P(OEt)3, MeCN

Scheme 37

Reaction of 2-alkoxy-1,3-benzodithiolene 287 or 1,3-benzodithiolylium fluoroborate 288 with P(OMe)3 takes place in acetonitrile in the presence of NaI to give 2-dimethoxyphosphinyl-1,3benzodithiole 289 in high yield (Scheme 38) <2002M1055>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

S

O

Me

S

Me

i, ii, iii

S

82%

S

O OMe P OMe

iii

S

82%

S

289

287

141

BF4–

288

i. HBF4, Ac2O; ii. Et2O; iii. P(OMe)3, NaI, MeCN

Scheme 38

Phosphorylated 1,3-dithiolenes 291 have been isolated as side products in the synthesis of tetrathiafulvalene derivatives 292 from acetylenes 290, CS2, and P(OMe)3 (Equation (49)) <2002JHC691>. i. CS2 ii. P(OMe)3 iii. MeOH Ph

R

S P

R Ph 290

S

OMe OMe

R

S

S

Ph

Ph

S

S

R

+

291

ð49Þ

292

36 –37%

R = H, COOMe

Thiphosphirane 154, containing a CPNS fragment, can be prepared by the method shown in Scheme 18.

(ii) Functions bearing one sulfur and two phosphorus substituents A methanediphosphonic ester, containing 4-MeSC6H4-S group 295, has been prepared by recently developed method, which is based on the reaction of compound 293 with disulfide 294 in the presence of ButOK <1998JAP10130284>. Salt 296 has been obtained on further hydrolysis of the ester 295 (Scheme 39) <1999JAP11080176>.

O ( PrOi)2P

O P(OPri)2 293

ButOK, PhMe

S S

S (PriO)2P O 295

+ MeS

O (PriO)2P

SMe 294

SMe

i. MeOH, HCl ii. NaOH, H2O PO3HNa MeS

S PO3HNa 296

Scheme 39

Initial exploratory results on the [4+2]-cycloaddition potential of the hetero-1,3-diene system of 297 were provided by the reactions between the heterocyclic compounds 297 and the phosphoalkynes 298. It was shown that the intermediate 299 reacts with one more molecule of RCP to form compound 300, which then reacts with elemental sulfur to give compound 301 in high yield (Scheme 40) <2002EJO1664>.

142

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

P

S

+ RC P P

P P

86–92%

R 297

298

RC P

R

P

R P

P

R

R

P P

299

R 300

1/8, S8, Et3N, toluene, 25 °C

81%

S

But But P S P R = But, Me2CEt, Me-c-Hex

S

R

S

R

Toluene, 100 °C

R

P

But

P But 301

Scheme 40

(iii) Functions bearing one sulfur, one nitrogen, and one phosphorus substituent The reaction of the unsaturated compound 302 with dimethyl diazomethane 303 leads to the formation of pyrazoline 304 stereoselectively, which has been used in cyclopropane synthesis (Equation (50)) <1999T14791>. O O EtO P EtO

O S

O EtO P EtO

Et2O, rt, 6 h + Me2CN2

S

Tol-p N N

ð50Þ

Me

Tol-p

Me

303 302

304

Isothiazolylphosphonate 305 has been demonstrated to react with an ethereal solution of diazomethane to give a mixture of the two tautomers of 1- and 2-pyrazolines 306 and 307 (Equation (51)) <2001T5455>.

Ar

NEt2 Et2O

EtO

N

S EtO P O O O

OEt O P O N S O N N

EtO

+ CH2N2

85% total yield

Ar

305

+

OEt EtO O P O H N S O N N Ar

NEt2

306

NEt2

ð51Þ

307

Ar = 4-MeOPh

1,4,2-Oxazaphospholine 309 has been prepared by the [4+1]-cycloaddition reaction of heterodiene 308 with 4-chlorobenzenethiol and triethyl phosphite (Equation (52)) <1995ZOB948>.

O

Cl

F3C S N

i, ii Ph

Ph

N 308

CF3

O P OEt EtO OEt 309

i. 4-Cl-C6H4SH, KOH; ii. P(OEt)3, CH2Cl2

Cl

ð52Þ

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 6.04.1.2.3

143

Functions bearing selenium and phosphorus substituent

(i) Functions bearing two selenium and one phosphorus substituent Triselenocarbonate 310 has been used in the synthesis of 2-triphenylphosphino-1,3-diselenole trifluoroborate 311. Compound 311 has been prepared by a one-pot reaction (Scheme 41) <1996JOC2877>.

E

Se Se

E

CF3SO3Me

Se

+

E

Se

E

Se

SeMe

NaCNBH3

E

Se SeMe

E

Se H

i. HBF4, Et2O ii. Ph3P

E E

310

+

Se PPh3 – Se H BF4

311

Scheme 41

Similar to sulfur-containing compounds 273, seleno-containing analogs 313 were obtained from diazocompounds 271 and diselenides 312 (Equation (53)) <1996S1232>. O (R1O)

BF3·Et2O, CH2Cl2, 25 °C

2PCHN2

+

O SeR R1O P OR1 SeR

R–Se–Se–R

271

312

ð53Þ

313 –

–

R1 = Me; R = Ph; –R-R– = –CH2CMe2CH2, –CH2CH(But)CH2

(ii) Functions bearing one selenium and two phosphorus substituents 1,2,4-Selenodiphospholes 314, RCP and elemental Se were used as precursors for the synthesis of 5-seleno-1,4,7,8-tetraphosphatetracyclo[4.3.0.02,4.03.7]non-8-enes 315 (Equation (54)) <1999S1642, 2000CC1745, 2001HAC406>. But But P P

But P P

+ Se

But

Bu

tC

P + Se

314

Se P

But

P 315

ð54Þ

But

(iii) Functions bearing one selenium, one sulfur, and one phosphorus substituent Phosphonates, containing sulfur and selenium atoms 317, have been obtained by the reaction of -phosphoryl sulfoxides 316 with phenyl selenobromide <1995TL2871, 1997T2959>. As in the case of the sulfuric analogs <1997T2959>, this reaction occurs stereoselectively (Equation (55)). Me

R (R1O)

2P

O

S O 316

i. BuLi, THF ii. PhSeBr

PhSe (R1O)

2P

O

R S O 317

Me

ð55Þ

144

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

6.04.2

FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLY A GROUP 15 ELEMENT

6.04.2.1

Functions Bearing Chalcogen and Boron

Only one example of the synthesis of compounds bearing two boron atoms and one oxygen has appeared in the literature since COFGT (1995). The reaction of 1,2-bis(diisopropylamino)-2,5dihydro-1H-1,2-diborole 318 with carbon monoxide leads to the formation of the product 319. Similarly, compound 321 can be obtained from unsaturated 1,2-diborole 320 (Scheme 42) <1998EJI459>. N(Pri)2 (Pri)2N CH2 B O B

N(Pri)

2

(Pri)2N

B

B

CH2

CO, THF 44%

B O B CH2 N(Pri )2 N(Pri)2

318

319

N(Pri)2 B B

N(Pri )2

CO, THF

N(Pri)2

50%

N(Pri)2 O B B B B O (Pri)2N

320

N(Pri)2 321

Scheme 42

6.04.2.2 6.04.2.2.1

Functions Bearing Chalcogen and Silicon Functions bearing oxygen and silicon

(i) Functions bearing two oxygen and one silicon substituent(s) [(3-Benzyltetrahydro-2-furanyl)(dimethoxy)methyl](trimethyl)silane 323 has been obtained from compound 322, Ph3P+CH2OMeCl, and Me3SiCl by the electrochemical reaction. Also compound 323 was synthesized using acyclic monomers. This reaction occurs stereoselectively (Equation (56)) <2002JA10101>. Ph O

O 322

i

ii

iii 80%

O

Ph OMe OMe SiMe3

ð56Þ

323

i. Ph3P+CH2OMeCl–; ii. Me3SiCl; iii. 0.5 M Et4NOTs, MeOH, 8 mA, 2.0 F/mol

In the presence of tertiary amine, compound 324 undergoes nucleophilic substitution by phenol or benzylalcohol at a bromine-linked carbon atom to give asymmetric trimethylsilyl acetals 325, which are also accessible directly from silyl methyl ether 326 without preliminary isolation of compound 324 <2001TL4557>. Furthermore, compounds 325 can be obtained from 1-octanole (Scheme 43) <1999MI469>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen ROH, EtN(Pri )2

Br MeO

SiMe3

OR MeO

84%

324

i. Br2 ii. ROH, EtN(Pri)2

MeO

84%

SiMe3

145

SiMe3

326

325

R = Ph, Bu, 1-octane

Scheme 43

1-Substituted-1-alkoxy-1,3-diene 327 has been brominated by N-bromosuccinimide to give compound 328 on subsequent washing of the reaction mixture with sodium bicarbonate solution (Equation (57)) <1999SL1841>. i. MeOH, bromosuccinimide, THF ii. NaHCO3, H2O iii. Et2O

EtO Me3Si

OMe Me3Si

CH2

Br

ð57Þ

OMe

327

328

Mg-promoted cross-coupling reactions of aromatic carbonyl compounds 329 with trimethylsilyl chloride in DMF at room temperature bring about reductive carbon–silicon bond formation to give the corresponding -trimethylsilyl alkyltrimethylsilyl ethers 330 selectively in good yields (Equation (58)) <1995CL829>. O Ph

Me3SiCl, Mg, DMF OEt

Ph EtO

56%

329

O SiMe3 SiMe3

ð58Þ

330

(ii) Functions bearing one oxygen and two silicon substituents Epoxide 331 selectively reacts with Me3SiCl in the presence of BusLi to yield di-(trimethylsilyl)epoxide 332 (Equation (59)) <2002PIAWO2002053549>. i. Me3SiCl, BusLi, hexane ii. THF iii. HCl, H2O

O (CH2)9-Me

O

Me3Si

ð59Þ (CH2)9-Me

Me3Si

52%

331

332

Silylation of epoxide 333 by Me3SiCl also selectively leads to the formation of 1,1-disilyl epoxide 334 (Equation (60)) <2002SL553>.

O But Me

CH2

i. TMEDA, BusLi, Et2O, cyclohexane ii. Me3SiCl 58%

Me 333

O

Me3Si But Me

CH2

Si

ð60Þ

Me 334

Allyl ether 337 can be accessed by the electrochemical reaction of compounds 335 and 336 (Equation (61)) <2001JEC55>.

146

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

Me3Si

OMe Sn(Bun) SiMe3

Bu4N+BF4– , CH2Cl2

OMe

H2C CHCH2SiMe3

+

98%

335

CH2

Me3Si SiMe3

ð61Þ

337

336

Substituted benzotriazole 340 containing the bis(trimethylsilyl)phenoxymethylene group has been obtained by the reaction of 1-(phenoxymethyl)-1H-1,2,3-benzotriazole 338 with 2 equiv. of Me3SiCl (Scheme 44) <1999T11903>.

OH

N N

+

N CH2Cl

N

NaH, DMF

N N CH2OPh

85%

338

N N

i. LiN(Pri )2, THF ii. Me3SiCl, THF

N

86%

N

N CH2OPh

N

Me3Si

i. LiN(Pri )2, THF ii. Me3SiCl, THF

N

36%

N

N Me3Si

OPh SiMe3 340

OPh

339

338

Scheme 44

The reaction of complex 341 with pivaldehyde afforded the di(hypersilyl)compound 342 (Equation (62)) <1997CB1709>. SiMe3 Me3Si Si SiMe3 + ButCHO O Li O O

Pentane

(Me3Si)3Si

OH Si(SiMe)3 342

ð62Þ

341

Oxidation of the unsaturated compound 343 by MCPBA in dichloroethane leads to the formation of epoxide 344 (Equation (63)) <1997JCS(P1)2279>. Me3Si

(CH2)4COOMe

Me3Si

MCPBA, CH2Cl2

Me3Si

97%

Me3Si

343

O (CH2)4COOMe

ð63Þ

344

Benzyl-N,N-diethylcarbamate 345 reacts with BuLi and trimethylsilyl chloride to give bissilylated product 346 (Equation (64)) <1995SC3347>. O Et2N

O

Ph

BuLi, THF Me3SiCl 60%

345

Ph Me3Si

O SiMe3

O NEt2

ð64Þ

346

(iii) Functions bearing one oxygen, one sulfur, and one silicon substituent The reaction of benzoquinones 347 or 348 with chloromethylenesulfinic acid 349 and subsequent silylation of the reaction mixture yielded benzoxathiole 1,1-dioxides 350 (Scheme 45) <1996AP361>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

147

O F

O

O

F 347

O i, ii, iii, iv, v + ClH2C S OH 72%

F

Me Si But S O Me

O

MeO

O

349

F

i, ii, iii, iv, vi

+ 349

72% O 348

350

i. HCl, H2O; ii. NaOH, H2O; iii. Me2SO4; iv. Li(Pri)2, THF; v. ButSiMe2Cl, HHF; vi. ButSiMe2Cl

Scheme 45

Substituted trimethylsilylmethane 352 has been obtained by consecutive reactions of the ether 351 with ButLi, trimethylgermyl bromide, and trimethylsilyl chloride in THF (Equation (65)) <2000JCS(P1)2677>. PhSCH2OMe

i, ii, iii, iv

Me3Ge

90% 351

OMe SPh SiMe3

ð65Þ

352

i. ButLi, THF; ii. Me3GeBr, THF; iii. ButLi, THF; iv. Me3SiCl

(iv) Functions bearing one oxygen, one silicon, and one nitrogen substituent 1-(Chloromethyl)benzotriazole 353 has been lithiated by LDA to give 3,3-disubstituted-1-oxiranylbenzotriazoles such as 354 on further reaction with ketones, which have been silylated by trimethylsilyl chloride to yield substituted oxiranylbenzotriazoles such as 355 bearing oxygen, silicon, and nitrogen at an sp3-carbon atom (Scheme 46) <2003JOC407>.

N

N

i, ii, iii

N

iv, v

N

69%

N

N

N

N CH2Cl 353

N O Et

Et

Et

354

SiMe3 O

Et 355

i. 3-pentanone, LiN(Pr-i)2, THF; ii. BuLi; iii. Me3SiCl; iv. BuLi, THF; v. Me3SiCl

Scheme 46

Trimethylsilyl allylbenzotriazole 357, obtained by the silylation of the substituted benzotriazole 356, has been demonstrated as a convenient reagent for the synthesis of carbonyl compounds (Equation (66)) <1995JOC7589>. N N N EtO 356

Me3SiCl, BuLi, THF

N N N Me3Si EtO

ð66Þ

357

Some other benzotriazoles substituted with a trimethylsilyl group 358 have been obtained by the reaction of methoxymethyl benzotriazole with alcohols and trimethylsilyl chloride <1999T11903>.

148

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen N N N RO

SiMe3

358 R = Ph, 4-MeOPh, Et, Me, But

The reaction of O-allenyl--D-xylofuranoses with Me3SiCl and ClSO2NCO afforded silyl derivatives of -D-xylofuranose 359 with high yields <2000TA3131>.

Me O Me

H O OR

O H O Me3Si HN

CH2

O 359

6.04.2.2.2

Functions bearing sulfur and silicon

(i) Functions bearing two sulfur and one silicon substituent(s) 2-Trimethylsilyl-1,3-dithiane 360 chemoselectively reacts with vinyl epoxides 361 to give compounds 362 (Equation (67)) <2002JA14516>. CH2 O

S S 360

+ SiMe3

R

CH2

i, ii, iii 76–88%

R HO

S

SiMe3 S

ð67Þ

361 362 i. HMPT, ButLi, THF, hexane; ii. THF; iii. NH4Cl, H2O R = CH2OCHPh, CH2OSiBuPh2, cyclohexyl

Substituted 2-silyl-1,3-dithianes have been obtained by various methods: the reaction of 2,4dithiacyanopentanes with sodium in liquid ammonia and phenoxymethoxytrimethylsilylmethane <2002SL1447>, treatment of octanal with 1,3-dimercaptopropane and Me3SeCl <2002TA1825>, from 1,3-dithiane with diphenylfluorosilyl ether <2002JA7363>, by the reaction of 2-trimethyl1,3-dithiane with triphenylsilyl ether of iodoethane <2002OL1787>, by silylation of 2-substituted 1,3-dithianes with Alk3SiCl or disilylic ethers <2002OL2957, 2002S552, 2001CL476, 2000TL321>, from 2-trimethylsilyl-1,3-dithianes with azulenes <2001S1346>, by the reaction of 2-triphenylsilyl-1,3-dithianes with 5-bromopentanal acetal <2001JOC8983>, by the condensation of aromatic aldehydes with 1,3-dimercapropropane and subsequent silylation of the reaction mixture with Me3SiCl <2000JOM220>. Substituted 2-silyl-1,3-dithianes, obtained by these methods, have been used for the synthesis of different derivatives of carbonyl compounds, including natural products. 2-Trimethylsilyl-1,3-dithiolane 366 has been obtained by the reaction of compounds 363, 364, or 365 with 1,2-dimercaptoethanol (Scheme 47) <2001TL4557>. 2-Acetylthiotetrahydropyran gives silylated 2-phenylthiomethylthiotetrahydropyran in 67% yield on reaction with chloromethylthiobenzene and Me3SiCl in THF <2002PS709>. The reaction of disilane 367 with diphenyldithiomethane 368 leads to the formation of bis(disilyl)ether 369 (Equation (68)) <2000JOM12>.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

149

i, ii, iii

Me3SiCH2OMe 363 Br

S

ii, iii

MeOCHSiMe3 364

SiMe3 88%

S 366

OMe iii

Me3SiCHOBun 365

i. Br2; ii. BuOH, EtN(Pri)2; iii. HSCH2CH2SH, BF3-Et2O

Scheme 47

PhS

Cl Me Si Me Me Si Me Cl

+

Bu, THF

2PhSCH2SPh

SPh

Me Si Me Me Si Me

368

PhS

367

ð68Þ

SPh 369

1,3-Disilacyclohexanes 371 and 373 are formed by silylation of bis(alkylthio)methyllithium with chloro(chloromethyl)dimethylsilane 370 and 372 followed by ring closure in the presence of a base. The spiro-fused disilacyclohexane ring 373 is structurally strain free, like cyclohexane. The proposed reaction mechanism involves a silacyclopropane intermediate (Scheme 48) <1999ICA231>.

CH2Cl Me Si Me MeS

MeS

Me Si Me MeS SMe Si SMe Me Me 371

LiN(Pri)2, THF

SMe 370

Me Me S S

Me Si CH2Cl Me 372

LiN(Pri)2, THF

S

Si S

S

Si S Me Me 373

Scheme 48

Norbor-5-en-2,3-dicarboximide 374 reacts with thiophenol and 2-methylsilyl-1,3-dithiane to give compound 375 (Equation (69)) <1998T12361>. OMe

H O N

OMe

+

374

I

S

+

I N

S H O

OMe

H O

SH

SiMe3

OMe

H HO

S Me3Si 375

S

ð69Þ

150

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

(ii) Functions bearing one sulfur and two silicon substituents Bis(trimethylsilyl)methane sulfonamide 377 has been obtained by the reaction of tris(trimethylsilyl)methanesulfonyl chloride 376 with H2O, PCl5, and piperidine (Equation (70)) <2000CJC1642>.

Cl

i. H2O, THF ii. PCl5, Et2O iii. Piperidine, CH2Cl2

O SiMe3 S SiMe3 O SiMe3

O N S O

376

SiMe3

ð70Þ SiMe3

377

Reductive lithiation of (PhS)2CH(SiMe2)3CH(SPh)2 378 or deprotonation of PhSCH2(SiMe2)3CH2SPh 380 has been used to afford PhSCHLi(SiMe2)3CHLiSPh, which was silylated with Me2SiCl2 or (SiMe2Cl)2 to give the tetrasilacyclohexane 381 or pentasilacycloheptane 379 (Scheme 49) <1999SL1772, 2000JOM12>. Me PhS Me Si PhS Me Si Me SPh Me Si SPh Me

Cl Me Si Me Me Si Me Cl

+

Me Me Me Si Si Me PhS Si Me Me Si Me Me Si SPh Me Me

(4-ButC6H4)2.Li, THF

378

379 Me SPh Me Si Me Si Me Me Si Me SPh

Me2SiCl2,

PhS

Me Si Si Me Me Me Si Si SPh Me Me Me Me

BusLi

380

381

Scheme 49

(iii) Functions bearing one sulfur, one silicon, and one nitrogen substituent The lithiation site of 2-trimethylsilyl-N-BOC-pyrrolidine 382 is strictly dependent on the reaction temperature; at 78 C the anion of 382 reacts with dimethyl disulfide to give in solely 2,2disubstituted product 383 (Equation (71)) <1999JPC455>. i. BusLi, TMEDA ii. Me2S2 (–78 °C to rt) SiMe3 N BOC

SMe

ð71Þ

N SiMe 3 BOC

76%

382

383

Nonregioselective reaction of 1-chloromethylbenzotriazole 384 with ButSH and Me3SiCl leads to the formation of the mixture of compounds 385 and 386 (Equation (72)) <1999T11903>. SH

N N N CH2Cl 384

+

Me

Me

SiMe3

(1) i, ii, iii (2) iv, v, vi

N

N N

+

N

N

Me Me3Si

80% 385

N SBut

Me3Si

SBut

10% 386

i. NaH, DMF; ii. H2O; iii. CH2Cl2; iv. LiN(Pri)2, THF; v. Me3SiCl, THF; vi. NH4Cl, H2O, Et2O

ð72Þ

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 6.04.2.2.3

151

Functions bearing selenium and silicon

No new examples of the synthesis of the functional groups bearing selenium and silicon have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.2.3 6.04.2.3.1

Functions Bearing Chalcogen and Germanium Functions bearing two oxygen and one germanium substituents

Since 1994 only two examples of a functional group of such type have been reported. Reaction of the diazagermylenes 387 with dichlorocarbene leads to the formation of the mixture of compounds 388 and 389 (Equation (73)) <1998MI729>. SiMe3 N Ge N SiMe3

SiMe3 N Cl Ge OBut N Cl SiMe3

CHCl3, ButOK, hexane, pentane

SiMe3 N Cl Ge OBut N OBut SiMe3

+

388

387

ð73Þ

389

Unsaturated ether 390 reacts with tri-2-furylgermane to give t-butyldimethylsilyl acetal 391 (Equation (74)) <2001MI461>. OSiMe2But

R

+ O

OMe

3

O

GeH

3

R

Ge OSiMe2But

ð74Þ

OMe

390

391

6.04.2.3.2

Functions bearing one oxygen, one sulfur, and one germanium substituents

Compound 393, bearing oxygen, sulfur, and germanium, has been obtained in several steps by the reaction of ether 392 with Me3GeBr and in one step from compound 394 (Scheme 50) <2000JCS(P1)2677>.

PhS-CH2-OMe

i, ii

i, ii, iii

OMe Me3Ge C SPh GeMe3

392

i, ii, iii

OMe Me3Ge C SPh H

92%

(Step 1)

393

394

i. ButLi, THF; ii. Me3GeBr, THF; iii. NH4Cl, H2O

Scheme 50

Compound 395 has been obtained in a similar way to the above-mentioned methods from ethers 392 and 394 (Scheme 51) <2000JCS(P1)2677>.

PhS-CH2-OMe

i, ii

i, iii, iv

OMe Me3Ge C SPh SiMe3

i, iii, iv

OMe Me3Ge C SPh H

392

(Step 1) 395 90% 394 i. ButLi, THF; ii. Me3GeBr, THF; iii. Me3SiCl, THF; iv. NH4Cl, H2O

Scheme 51

152

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

6.04.3

FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY A GROUP 15 ELEMENT OR A METALLOID

6.04.3.1 6.04.3.1.1

Functions Bearing Oxygen and a Metal Functions bearing two oxygens and a metal

No new examples of the synthesis of the functional groups bearing two oxygens and a metal have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.3.1.2

Functions bearing oxygen, silicon, and a metal

Methoxymethyltrimethyl silane 396 on treatment with BuLi undergoes regioselective lithiation to give in good yield 397 metallated at the methylene carbon (Equation (75)) <2000JOM87>. Li MeOCH2SiMe3

BuLi, THF

MeOCHSiMe3

ð75Þ

95% 396

6.04.3.1.3

397

Functions bearing oxygen and two metals

No new examples of the synthesis of the functional groups bearing oxygen and two metals have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.3.2 6.04.3.2.1

Functions Bearing Sulfur and a Metal Functions bearing sulfur, oxygen, and a metal

Compounds such as 399, bearing functional groups of this type, have been obtained by the reaction of trimethylsilyl ethers such as 398 with BuLi. Germanium-containing analogs such as 401 were generated directly in the reaction mixture to give bisdigermenyl ethers such as 402 on further reaction with Me3GeBr or to give silylated compounds such as 403 on treatment with Me3SiCl (Scheme 52) <2000JCS(P1)2677>.

Me3Si

OMe C SPh H

BuLi, THF

398

OMe Me3Ge C SPh H 400

ButLi, THF

OMe Me3Ge C SPh Li 401 90%

Me3Si

Li C SPh OMe 399

Me3GeBr 92%

OMe Me3Ge C SPh GeMe3 402

MeSiCl

OMe Me3Ge C SPh SiMe3 403

Scheme 52

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 6.04.3.2.2

153

Functions bearing two sulfurs and a metal

Compound 407, which can be used for the synthesis of macrolide antibiotic Roflamycoin, has been obtained by the reaction of compounds 404–406 with BuLi (Equation (76)) <1997JA2058>.

S S

O

H O

SnBu3 + SnBu3

404

BuLi +

LiCH2OCH2Ph

S

56%

S

406

OH OH O

SnBu3

405

Ph

ð76Þ

407

Besides, 1,3-dithiane 404 has been converted into 2-deuterated-1,3-dithiane 408 bearing one Bu3Sn group <2001TL5001>.

S SnBu3 S

D 408

Dithioacetals such as 409 have been demonstrated to react with Bu3SnCl to give tributylstannylthioacetals such as 410, which can be used for the synthesis of ,-unsaturated ketones (Equation (77)) <1995T2515>.

SPh PhS C H

i. BuLi, THF, hexane ii. Bu3SnCl Ph

97%

SPh (Bun)3Sn C SPh

409

Ph

ð77Þ

410

Trimethylstannylthioacetal 411 undergoes Michael addition to 2-cyclohexenone to yield the ketone 412 (Equation (78)) <2000AG(E)414>.

SMe MeS C SnMe3 H 411

2-cyclohexenone HMPT, THF 77%

SMe O

C MeS

SnMe3

ð78Þ

412

By the reaction of pentadiene 413 with 2-methylene-1,3-dithiane 414, compound 415 has been generated in the reaction mixture and then alkylated to produce different dithiane polyenes 416 and 417, which have been demonstrated to be convenient reagents for the stereoselective synthesis of decahydronaphthalenes (Scheme 53) <1995TL3473>. Li-N,N-diisopropyl-3-amino-1,3-benzothiaborolide 418 has been prepared by the multistep synthesis starting from thioanisole (Equation (79)) <1998JOM2379>.

154

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

Me

Br

i, ii

Me

413

Li

415

Me

S

S

S

S 416

Br SnBu3 SnBu3 Me

S S 417 S 414

i. BuLi, THF; ii. S

Scheme 53 Me S Ph

i, ii

iii, iv

v

S Li B N(Pri )2 418

ð79Þ

i. BuLi, hexane; ii. Bu2SnCl2, pentane, hexane; iii. BCl3, pentane; iv. Pr2i NH, CH2Cl2; v. ButLi, THF

6.04.3.2.3

Functions bearing sulfur, boron, and a metal

No new examples of the synthesis of the functional groups bearing sulfur, boron, and a metal have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.3.2.4

Functions bearing sulfur, silicon, and a metal

No new examples of the synthesis of the functional groups bearing sulfur, silicon, and a metal have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.3.2.5

Functions bearing sulfur and two metals

No new examples of the synthesis of the functional groups bearing sulfur and two metals have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

6.04.3.3

Functions Bearing Selenium and a Metal

No new examples of the synthesis of the functional groups bearing selenium and a metal have appeared in the literature since COFGT (1995) <1995COFGT(6)103>.

REFERENCES 1969ZC201 1971S16 1977UK685

J. Gloede, L. Haasse, H. Gros, Zeitschrift fuer Chemie 1969, 9, 201–213. R. Feinauer, Synthesis 1971, 16–26. V. G. Granik, A. M. Zhidkova, R. G. Glushkov, Usp. Khim. 1977, 46, 685–711. (Chem. Abstr. 1977, 87, 21650).

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 1979T1675 1985HOU(E5)3 1990T7429 1995COFGT(6)103 1994JOC5877 1994JOC7934 1994SL84 1995AP609 1995CL829 1995H131 1995JA11839 1995JAP07109289 1995JMC3558 1995JOC1546 1995JOC6431 1995JOC6987 1995JOC7589 1995JOC8310 1995MI218 1995MI417 1995S168 1995SC3347 1995SL703 1995T2515 1995T6651 1995TL2871 1995TL3473 1995TL6257 1995TL9385 1995TL9409 1995ZOB948 1996AP361 1996JA12848 1996JCR(S)466 1996JOC2877 1996JOC9538 1996JOC9585 1996KFZ31 1996KTK374 1996PIAWO9633199 1996PS295 1996S1196 1996S1232 1996T10053 1996T753 1996TL3497 1996TL3915 1996TL711 1997CB1709 1997JA2058 1997JCS(P1)2279 1997JOC3109 1997PS335 1997PIAWO9739004 1997S1077 1997S407

155

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1997T13449 1997T2959 1997TL4521 1997TL6421 1998BRP2316945 1998CC1459 1998CC43 1998CR409 1998EJI1539 1998EJI459 1998GEP(O)19737923 1998JA3664 1998JAP10130284 1998JOC7128 1998JOM2379 1998JPR51 1998MI729 1998PIAWO9834940 1998PS141 1998SL283 1998T12361 1999AG(E)1928 1999CC1927 1999CC499 1999CL879 1999ICA231 1999JAP11080176 1999JCS(P1)1151 1999JCS(P1)937 1999JOC1766 1999JPC455 1999MI2270 1999MI325 1999MI397 1999MI469 1999PS337 1999PS313 1999S1642 1999SL1772 1999S751 1999SL1633 1999SL1841 1999SL1923 1999T11903 1999T14791 1999TL6891 1999TL7079 2000AG(E)1261 2000AG(E)414 2000BMCL2343

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Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen 2000CAL397 2000CC1745 2000CJC1642 2000HCA3163 2000JA10242 2000JAP281690 2000JCS(P1)2677 2000JMC4563 2000JOC1886 2000JOC7512 2000JOC8940 2000JOM12 2000JOM220 2000JOM87 2000MI92 2000PS107 2000S633 2000SL125 2000SL1464 2000T10101 2000TA3131 2000TL10091 2000TL321 2000TL3643 2000TL7327 2000USP6143923 2001AG(E)1247 2001BMCL1451 2001CC1336 2001CEJ2332 2001CL476 2001EJO933 2001HAC250 2001HAC406 2001IJC(B)500 2001JA5130 2001JA8408 2001JCS(P2)522 2001JEC55 2001JOC8983 2001MI1035 2001MI129 2001MI461 2001MIP2173321 2001PIAWO0109146 2001S1346 2001SL467 2001SL473 2001T3909 2001T5455 2001T669 2001TA923 2001TL4557 2001TL4573

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158

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

2001TL4819 2001TL5001 2001TL8475

A. Dondoni, G. Lathauwer, D. Perrone, Tetrahedron lett. 2001, 42, 4819–4824. J.-C. P. Cintrat, F. Pillon, B. Rousseau, Tetrahedron Lett. 2001, 42, 5001–5003. M. Lecouvey, I. Mallard, T. Bailly, R. Burgada, Y. Leroux, Tetrahedron Lett. 2001, 42, 8475–8478. 2002DOK61 A. B. Koldobskii, V. E. Vakhmistrov, E. V. Solodova, O. S. Shilova, V. N. Kalinin, Doklady Akademii Nauk 2002, 387, 61–64. (Chem. Abstr. 2003, 138, 304131). 2002DP143 S. S. Ramos, P. F. Santos, L. V. Reis, P. Almeida, Dyes Pigm. 2002, 53, 143–152. 2002EJO1664 J. Dietz, T. Schmidt, J. Renner, U. Bergstrasser, F. Tabellion, F. Preuss, P. Binger, H. Heydt, M. Regitz, Eur. J. Org. Chem. 2002, 1664–1676. 2002EUP1215201A2 Bellus, D.; Dondoni, A. Eur. Pat., 1215201A2 (2002) (Chem. Abstr., 2002, 137, 33135). 2002GEP10114352 Blum, H.; Pustovit, Y.; Greb, W.; Roeschenthaler, G.-V. Ger. Pat. 10114352 (2002) (Chem. Abstr., 2002, 136, 310034). 2002HCA2383 T. Nishio, K. Shiwa, M. Sakamoto, Helv. Chim. Acta 2002, 85, 2383–2393. 2002JA10101 B. Liu, S. Duan, A. C. Sutterer, K. D. Moeller, Journal Am. Chem. Soc. 2002, 124, 10101–10111. 2002JA13678 S. Kobayashi, H. Shimizu, Y. Yamashita, H. Ishitani, J. Kobayashi, J. Am. Chem. Soc. 2002, 124, 13678–13679. 2002JA14516 A. B. Smith III, M. S. Pitram, M. J. Gaunt, S. A. Kozmin, J. Amer. Chem. Soc. 2002, 124, 14516–14517. 2002JA7363 M. W. Mutahi, T. Nittoli, L. Guo, S. Luxuan, M. Scott, J. Am. Chem. Soc. 2002, 124, 7363–7375. 2002JAP2002105058 Ono, M.; Sen, M. Japan Patent 2002, 2002105058 (Chem. Abstr., 2002, 137, 200977). 2002JCS(P1)1568 Z. Casar, I. Leban, A. M. Marechal, D. Lorcy, J. Chem. Soc., Perkin Trans. 1 2002, 1568–1573. 2002JHC691 W. A. O. Sarhan, M. Murakami, T. Izumi, J. Heterocycl. Chem. 2002, 39, 691–694. 2002JMC2185 C. M. Szabo, Y. Matsumura, S. Fukura, M. B. Martin, J. M. Sanders, S. Sengupta, J. A. Cieslak, T. C. Laftus, C. R. Lea, H.-J. Lee, A. Koohang, R. M. Coates, H. Sagami, E. Oldfield, J. Med. Chem. 2002, 45, 2185–2196. 2002JOC6124 H. Kumamoto, M. Murasaki, K. Haraguchi, A. Anamyra, H. Tanaka, J. Org. Chem. 2002, 67, 6124–6130. 2002JOC7706 K. Tetsuya, S. Satoshi, M. Akira, J. Org. Chem. 2002, 67, 7706–7715. 2002M1055 W. A. O. Sarhan, M. Murakami, T. Izumi, Monatsh. Chem. 2002, 133, 1055–1066. 2002MI1111 V. M. Berestovitskaya, I. A. Litvinov, I. E. Efremova, L. V. Lapshina, D. B. Krivolapov, A. T. Gubaidullin, Russian J. General Chem. 2002, 72, 1111–1118. 2002MI335 B. P. Sharma, Indian Journal Heterocyclic Chem. 2002, 11, 335–336. 2002MI980 L. M. Burnaeva, V. F. Mironov, N. M. Azancheev, I. V. Konovalova, G. A. Ivkova, O. V. Yashagina, A. N. Pudovik, Russian J. General Chem. 2002, 72, 980–981. 2002MIP1333210 Xie, Y.; Li, Q.; Xie, Y.; Yan, X.; Qin, X. Chinise Patent 1333210 (2002) (Chem. Abstr., 2003, 138, 221705). 2002MIP2178793 Badmaev, A. V.; Mudryi, F. V.; Suchkov, A. V.; Milgotin, I. M.; Bogach, E. V.; Kuznetsov, A. A.; Bolshova, I. V. Russia Patent 2178793 (2002) (Chem. Abstr., 2003, 138, 221706). 2002OL1551 V. Capriati, L. Degennaro, R. Favia, S. Florio, R. Luisi, Org. Lett. 2002, 4, 1551–1554. 2002OL1787 P. Wipf, M. J. Soth, Organic Lett. 2002, 4, 1787–1790. 2002OL2957 L. Xin, D. A. Nicewicz, J. S. Johnson, Org. Lett. 2002, 4, 2957–2960. 2002PIAWO0290367 H. Dabak, A. E. Zarslan, F. Sahbaz, T. Aslan, PCT Int. Appl. WO 0290367 (2002). (Chem. Abstr. 2002, 137, 353175). 2002PIAWO2002053549 D. M. Hodgson, S. L. M. Norsikiun, I. D. Cameron, E. Gras, PCT Int. Appl. WO 2002053549 (2002). (Chem. Abstr. 2002, 137, 93678). 2002PS709 K. Sipia, T. Hase, J. Koskimies, J. Matikainen, J. Kansikas, Phosphorus, Sulfur, Silicon and the Related Elements 2002, 177, 709–727. 2002S2043 D. Ntirampebura, L. Ghosez, Synthesis 2002, 2043–2052. 2002S274 M. Berganer, P. Gmeiner, Synthesis 2002, 274–278. 2002S552 J.-P. Bouillon, F. Huguenot, C. Portella, Synthesis 2002, 552–556. 2002SL1447 A. Capperucci, V. Care, A. Degllnnocenti, T. Nacenthini, S. Pollicino, Synlett 2002, 1447–14450. 2002SL525 M. Monenschein, M. Brunjes, A. Krischning, Synlett 2002, 525–527. 2002SL553 J.-C. Marie, C. Courillon, M. Malacria, Synlett 2002, 553–556. 2002T2215 D. Krishnaswamy, V. V. Govande, V. K. Gumaste, B. M. Bhawal, A. R. A. S. Deshmukh, Tetrahedron 2002, 58, 2215–2226. 2002TA1825 A. Battaglia, E. Baldelli, G. Barbaro, P. Giorgianni, A. Guerrini, M. Monari, S. Selva, Tetrahedron: Asymmetry 2002, 13, 1825–1832. 2002TL6911 Y. Omata, A. Kakehi, M. Shirai, A. Kamimura, Tetrahedron Lett. 2002, 43, 6911–6914. 2002UKZ46 M. K. Bratenko, V. O. Chornous, M. V. Vovk, Ukr. Khim. Zh. 2002, 68, 46–51. (Chem. Abstr. 2003, 138, 89723). 2003JOC407 A. R. Katritzky, K. Mauju, P. J. Steel, J. Org. Chem. 2003, 68, 407–411. 2003USP3013918 Cowan, J. M.; Christopher, C. J.; Michael, J. US Patent 2003013918 (2003) (Chem. Abstr., 2003, 138, 8921). B-1970MI001 R. H. De Wolfe, in Carboxylic Ortho Acid Derivatives, Academic Press, New York, 1970, pp. 420. B-1979MI002 S. Patai, Ed., The Chemistry of Acid Derivatives, Supplement B, Interscience, New York, 1979.

Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen

159

Biographical sketch

Anatoliy M. Shestopalov was born in Khmel’nyts’kyy, Ukraine, in 1954. He studied chemistry and biology at the Lugansk Pedagogical Institute, where he received his M.Sc. in chemistry and biology in 1979. In 1985 he graduated with a Ph.D. (Development of the methods of synthesis, and investigation of chemical properties and biological activities of 3-cyanopyridine-2(1H)-thiones and products of their transformation) from the Institute of Chemical Aids of Plant Protection in Moscow, Russia. After a postdoctoral stay at the Zelinsky Institute of Organic Chemistry in Moscow, he received his ‘‘Doctor of Science’’ degree in chemistry (Quaternized azines in the synthesis of carbo- and heterocyclic compounds) in 1991 at the Zelinsky Institute of Organic Chemistry. He is now a chief scientist and head of the scientific group at the Zelinsky Institute of Organic Chemistry. His research interests include regio- and stereoselective synthesis of carbo- and heterocyclic compounds, multicomponent reactions, chemistry of N-, O-, S-, Se-containing heterocycles and chemistry of physiologically active compounds. He is an author of more then 200 scientific publications.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 111–159

6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) A. GU¨VEN Anadolu University, Eskis¸ ehir, Turkey 6.05.1 FUNCTIONS CONTAINING THREE GROUP 15 ELEMENTS 6.05.1.1 Functions Bearing Three Nitrogen Atoms 6.05.1.1.1 1,1,1-Triaminoalkanes 6.05.1.1.2 1,1,1-Trinitroalkanes 6.05.1.1.3 1-Amino-1,1-dinitroalkanes 6.05.1.2 Functions Bearing Three Phosphorus Atoms 6.05.1.3 Functions Bearing Three Arsenic Atoms 6.05.1.4 Functions Bearing Group 15 Elements 6.05.1.4.1 Functions bearing two nitrogen atoms and phosphorus atom 6.05.1.4.2 Functions bearing two nitrogen atoms and one arsenic atom 6.05.1.4.3 Functions bearing two nitrogen atoms and one antimony atom 6.05.1.4.4 Functions bearing two phosphorus atoms and one nitrogen atom 6.05.1.4.5 Functions bearing two phosphorus atoms and one arsenic atom 6.05.1.4.6 Functions bearing two phosphorus atoms and one antimony atom 6.05.1.4.7 Functions bearing two antimony atoms and one phosphorus atom 6.05.2 FUNCTIONS CONTAINING TWO GROUP 15 ELEMENTS AND ONE GROUP 13 OR 14 ELEMENTS 6.05.2.1 Functions Containing Two Group 15 Elements and One Group 13 Elements 6.05.2.1.1 Functions bearing two nitrogen atoms and one boron atom 6.05.2.1.2 Functions bearing two nitrogen atoms and one gallium atom 6.05.2.1.3 Functions bearing two nitrogen atoms and one indium atom 6.05.2.1.4 Functions bearing two nitrogen atoms and one thallium atom 6.05.2.1.5 Functions two phosphorus atoms and one gallium atom 6.05.2.1.6 Functions bearing two phosphorus atoms and one indium atom 6.05.2.1.7 Functions bearing one phosphorus, one nitrogen, and one boron atom 6.05.2.2 Functions Containing Two Group 15 Elements and One Group 14 Element 6.05.2.2.1 Functions bearing two nitrogen atoms and one silicon atom 6.05.2.2.2 Functions bearing two nitrogen atoms and one germanium atom 6.05.2.2.3 Functions bearing two phosphorus atoms and one silicon atom 6.05.2.2.4 Functions bearing two phosphorus atoms and one germanium atom 6.05.2.2.5 Functions bearing two phosphorus atoms and one tin atom 6.05.2.2.6 Functions bearing two antimony atoms and one silicon atom 6.05.2.2.7 Functions bearing one nitrogen atom, one phosphorus atom, and one silicon atom 6.05.2.2.8 Functions bearing one phosphorus atom, one antimony atom, and one silicon atom 6.05.3 FUNCTIONS CONTAINING ONLY ONE GROUP 15 ELEMENT 6.05.3.1 Functions Bearing One Nitrogen Atom and Two Silicon Atoms 6.05.3.2 Functions Bearing One Phosphorus Atom and Two Silicon Atoms 6.05.3.3 Functions Bearing One Arsenic Atom and Two Silicon Atoms 6.05.3.4 Functions Bearing One Antimony Atom and Two Silicon Atoms 6.05.3.5 Functions Bearing One Bismuth Atom and Two Silicon Atoms 6.05.3.6 Functions Bearing One Antimony Atom, One Gallium Atom, and One Silicon Atom

161

162 162 162 166 168 171 175 176 176 176 177 177 180 180 181 181 181 181 184 184 187 187 188 189 189 189 189 190 191 192 193 193 194 194 194 195 197 197 199 199

162

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

6.05.1

FUNCTIONS CONTAINING THREE GROUP 15 ELEMENTS

6.05.1.1

Functions Bearing Three Nitrogen Atoms

6.05.1.1.1

1,1,1-Triaminoalkanes

The use of a 2.1 molar ratio between conjugated azoalkenes 1 and diethylcyanomethylphosphonate 2 in tetrahydrofuran (THF) at room temperature with a catalytic amount of sodium hydride led to the direct formation of diethyl phosphonopyrrolo[2,3-b]pyrroles 4, via two sequential 1,4-addition reactions 3 (Scheme 1) <1994S181>.

R

Me

Me

Me

H

O CN NaH EtO N NHR1 1 + EtO P C N N R THF O P OEt N NHR1 H 44–77% EtO R 1 H 2 Me R1 = CO2Me, CO2But, 3 CONHPh, CO2Et, CONH2 R = CO2Me

MeO2C

N

R

N NHR1 NH2 N NHR1

EtO O P EtO R

Me 4

Scheme 1

Reactions of 1-aryl-2-methylthio-4-(N-arylamino)-4-phenyl-1,3-diazabuta-1,3-dienes 7 with -nitrosostyrenes 6, generated from -chlorooximes 5 in the presence of sodium carbonate, resulted in the formation of a mixture of products which are easily separated, and characterized as 1,4-diaryl-2-[N-arylamino(phenyl)methyleneamino]imidazole-3-oxide 8 and 1,4-diaryl2-[N-arylamino(phenyl)methyleneamino]imidazole 9 (Scheme 2) <1999(JCS(P1)615>. C6H4-p-R3

Cl

C6H4-p-R3

Na2CO3

OH

O

N

R3 = H, Cl, Me 6

5

Ph

N

C6H4-p-R1

Ph

NHC6H4-p-R2

N

N

SMe

Ph

+ p-R1-C6H4

NH O–

R1 = H, Me R2 = H, OMe, Cl

6

C6H4-p-R2 N

N

NC6H4-p-R2 SMe

7

Ph

C6H4-p-R1

NH

N+ C6H4-p-R3

p-R1-C6H4

44–53% 8

C6H4-p-R2 N

N NH

N C6H4-p-R3

31–38% 9

Scheme 2

Tris(alkylpyrazolyl)methanes 11 were prepared from the corresponding pyrazoles 10 under phase transfer conditions in 35–67% yields (Scheme 3) <2000JOM120>. The reaction of tris(pyrazolyl)methane 11 (R1 = R2 = H) with KOBut and paraformaldehyde followed by quenching with water yielded 12, which was then reacted with [Mn(CO)5SO3CF3], prepared in situ from Mn(CO)5Br and Ag(SO3)CF3, to afford complex 13 <2000JOM120>. The rhenium complexes of tris(alkylpyrazolyl)methanes 14 were prepared in refluxing toluene from the corresponding tris(alkylpyrazolyl)methanes 11 and Re(CO)5Br or Re(CO)5BF4 in 63–91% yield (Scheme 3) <2002JOM50>.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

163

R1 R2 N

R2 N N H

R1

10 1 = H,

R

Na2CO3, Bun4NBr

R2

N

N

H2O, CHCl3 1 rt then reflux, 3 days R 35–67%

H

N

N

N

R2

R1

Me, Ph, Pri, But

11

R2 = H, Me

11

+

R1 = R2 = H

Bu4NBr, Na2CO3, H2O CHCl3, Et2O HCHO, ButOK

O C + N N Mn C O C O N N O – F3C S O O 13

N N

N N

Mn(CO)5Br N N AgO SCF 3 3 78%

HOCH2

HOCH2

N N 12 R2

11 +

Toluene, reflux Re(CO)5Br or Re(CO)5BF4 63–91%

R1 = H, Me, Ph, Pri R2 = H, Me, Pri

H R2

R1 O N N C + N N Re C O X– C X = Br–, BF4– R1 O N N R1

R2 14

Scheme 3

[4+1]-Cycloaddition reaction of N-heterocyclic carbene, generated by thermal decomposition of 2trichloromethyl-1,3-imidazolidines 15, which is readily available from the condensation of the vicinal diamines and chloral, with isocyanates (16 and 17), obtained in situ via thermolysis of the readily available acyl azides, afforded compounds (18–20) in 70–71% yields (Scheme 4) <2002MI4289>.

O N

N

Ph N N O Ph 18 H N Ph

16 N C O 71%

Ph N CCl3 N H Ph 15

18 1 = 19 0.6

Ph N

∆ xylene

OH O

80 °C, 2 h then reflux 16 h

N H 19

[4 + 1]-cycloaddition 17

O

N C O 70%

N

N

Ph N N O Ph 20

Scheme 4

164

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

Phenyl isocyanide reacted with the N,N-(dimethylamino)benzotriazolylcarbene 22, which was generated from benzotriazol-1-ylmethylene-dimethyl-ammonium chloride 21, in a [1+2+2]cycloaddition, and then with nucleophiles to generate various hydantoins 23 in a one-pot procedure (Scheme 5) <1996JHC1935>.

N

Me

N N

N

+ Ph N C O Et3N, benzene morpholine Me 48% N Me

N + Me N Cl– Me

H 21

Me N

N

O

Ph

N

N

O

N Ph

O 23

22

Scheme 5

The methyl ester 27 was obtained in 80% yield in the presence of N-ethyldiisopropylamine (Hu¨nig’s base) 26 from the reaction of phenyl isocyanide with salt 25, 1-amino-5-methoxycarbonyl2,3-dimethyl-3H-imidazol-1-ium mesitylenesulfonate, which was prepared by direct amination of the 1,2-dimethyl-1H-imidazole-4-carboxylic acid methyl ester 24 with mesitylenesulfonylhydroxylamine (MSH) <1977S1> as the aminating agent (Scheme 6) <2001JOC8528>. MeO2C

N Me

MSH

NH2 – MSTSH N Me N Me MSTS = mesitylenesulfonate

+

MeO2C

CH2Cl2, rt 93%

N Me 24

25 –

Pr 25 +

Et

i

N Pri 26

MeCN 20 h, rt

MeO2C

NH N

+

Me Ph N C O

N Me

Me Me Ph N N

MeO2C

N N H

Ph N C O Et 80%

O

Pri N Pri

Me Me Ph N N N

O O

MeO2C

H N Ph

27

Scheme 6

The cycloadducts tetrahydro-1H-[1,3,5]triazino[1,2-a]quiazoline-1,3-(2H)-diones 29 were obtained from the reaction of 3,4-dihydroquinazoline 28 with phenyl isocyanate under mild conditions. When the reaction was carried out at temperatures above 110 C in 1,2-dichlorobenzene containing excess of phenyl isocyanide afforded 30 in 53% yield (Scheme 7) <2000MI2105>. The reactions of perfluoro-5-azanon-4-ene 31 with 2 equiv. of aniline and derivatives 32 in the presence of Et3N afforded the corresponding quinazolines 33 in 67–72% yields. The treatment of 31 with 2,6-dimethylaniline in a 1:1 stoichiometry afforded a six-membered heterocycle—the dihydroquinazoline derivative 34 in 61% yield. The reactions 31 with 1 equiv. of 2-nitro-, 4nitro-, or pentafluoroaniline 35 produced the diazetine derivatives 36. The fluorine atom in C-4 of 36 was substituted by the N-nucleophile to yield the compounds 37 in 57–68% yields (Scheme 8) <2000JFC263>.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) R1 N H Ph N O N N O Ph

Et2O, 0 °C R2

48–83% R2

N

165

R1 + Ph N C O

29

N 28

110 °C, reflu x 1,2-Cl2C6H4

R1= Me, 4-Me-C6H4 R2 = H, Me

O

R2

NR1 N Ph N O

53%

N Ph

O R1 = 4-Me-C6H4 R2 = Me

30

Scheme 7

CF2CF2CF3

F

NH2 N C4F9 + 2 equiv.

F3CF2CF2C

N

MeCN, Et3N 40 °C, 3 h 67–72%

R

31

32

CF2CF2CF3 N

NH

R

R = H, F, OMe

CF2CF2CF3 Me N CF2CF2CF3 N NH Me Me

NH2 31 +

Me MeCN, Et3N

Me

61%

R 33

34 F 31 + ArNH2 35

Et3N MeCN

CF2CF2CF3

N N F3CF2CF2C

Ar = 2-NO2-C6H4, Ar = 4-NO2-C6H4, C6F5

Ar 36

ArNH2 57–68% F CF CF C 3 2 2

N

NHAr CF2CF2CF3 N Ar 37

Scheme 8

The reaction of bis(dimethylamino)difluoromethane 40, which was produced from tetramethylchloroformamidinium chloride 39 and tetramethylammonium fluoride 38 in high yield, with dimethylaminotrimethylsilane, provided a rapid and facile access to hexamethylguanidinium fluoride 41 in 95% yield. 1,1,1-Trifluoro-2,2,2-tris(dimethylamino)ethane 42 was prepared from 41 and Me3SiCF3 in Et2O at 50 C in 96% yield (Scheme 9) <2000JFC159>. Orthoamide 45 was obtained from guanidininium chloride 43 and appropriate carbanion 44 in high yield (Scheme 9) <2002ZN(B)399>. The 1,3-dipolar cycloaddition reaction of various N-aryl-C-ethoxycarbonylnitrilimines 47, generated in situ from ethylhydrazono--bromoglyoxylate 48, with 1,3,4-benzotriazepin-5-ones 46 in the presence of Et3N regio- and chemoselectively afforded [1,2,4]triazolo[1,3,4]benzotriazepines 49 in 18–44% yields (Scheme 10) <2002MI1545>.

166

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) Me Me Cl N – Me Me N Me F + N Me Me + Me 38 Cl– 39

Me

+

N Me Cl

N Me

–

N Me Me 43

N

F Me N Me Me 40 0 °C, 2.5 h Me2NSiMe3 95% MeCN

Me Me N CF3 Me N N Me Me Me 42

Me

F

Me

CH2Cl2 0–5 °C, 5 h 95%

+

Me Me3SiCF3 –50 °C Et2O 96%

Me

+

N Me F

N Me

–

N Me Me 41

Me Me Et Et N Me NaH, THF + Et C C C H Et C C C C N 94% Me SiO Me OSiMe3 N 3 Me Me 44 45

Scheme 9

O

O Me N N H

N

O

+ EtO2C

Me

R1 = H,

–

R2

N N 47

R1

R1 Ph

1 week, rt 18–44%

Me CO2Et N N N N R1 H N

In situ

R2

N N N H

+

Et3N benzene

N H

N

R2

CO2Et

Br 48 R2 = Me, Cl, NO2

46

O

Me N CO2Et N

N N 1 N H R

R2 49

Scheme 10

6.05.1.1.2

1,1,1-Trinitroalkanes

The photolysis of tetranitromethane (TNM) 51 with 4-chloroanisole 50 in CH2Cl2 led to the formation of mainly 4-chloro-2-trinitromethylanisole 52 in 40–50% yields (Scheme 11) <1993ACS925>, with 1-methyl-4-propenylbenzene 53 to 1-methyl-4-(2-nitro-1-trinitromethylpropyl)benzene 54 <1998ACS745>, with 2,8-dimethyldibenzofuran 55 to mainly (50%) 2,8dimethyl-3-trinitromethyldibenzofuran 56 <1997ACS476>, with 1,4-dimethoxynaphthalene 57

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) OMe NO2 O2N NO2 NO2

+

OMe NO2 NO2 + NO2

CH2Cl2 hν

Cl

Cl 51

50

51

+

CH2Cl2 Me hν 29%

Me

O

40% 52 O2N

Me

NO2 NO2 NO2 OMe

Cl ON

NO2 NO2 Me

O2N 54

53

Me

Me NO2 NO2 NO2

50% O Me

56

Me +

51

CH2Cl2 19% Me

Me

hν

NO2

O

O

55

5%

Me

Me

O

OMe NO2 NO2 NO2

OMe

NO2 OMe

O2N +

OMe 18%

OMe +

167

51

CH2Cl2 hν

OMe 33%

58 O2N NO2 MeO NO2

57

NO2

MeO +

OH NO2 NO2 NO2

OMe

OMe

6%

14%

59

60

Scheme 11

to 1,4-dimethoxy-2-trinitromethylnaphthalene 58, 1,4-dimethoxy-2-nitro-1-trinitromethyl-1,2dihydronaphthalene 59, and 1,4-dimethoxy-2-trinitromethyl-1,2-dihydro-naphthalen-1-ol 60 (Scheme 11) <1997ACS1066>. The reaction of ,-unsaturated ketones of the adamantanes, 1-adamantan-1-yl-3-phenyl-propenone 62 and 1-adamantan-1-yl-4-phenyl-but-3-en-2-one 63 with trinitromethane 61 afforded the corresponding trinitroketones, 1-adamantan-1-yl-4,4,4-trinitro-3-phenyl-butan-1-one 64 and 1-adamantan-1-yl-5,5,5-trinitro-4-phenyl-pentan-2-one 65 in 61% and 93% yields, respectively (Scheme 12) <2001ZOR1872>. The destructive nitration of polynitrocarbonyl compounds 66 with HNO3–H2SO4 at 0 C yielded hexanitroethane 67 in 18–80% yields. Yield increased with electron-donor groups on 66 (Scheme 13) <1994ZOR29>. The compound 5,5-dinitro-6-(4-nitrophenyl)hexan-2-one 68 was also subjected to nitration with HNO3–H2SO4 to yield 1-nitro-4-(2,2,3,3,3-pentanitro-propyl)benzene 69 in 19% yield (Scheme 13) <1994ZOR1521>.

168

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) Ph O

O2N NO 2 NO2

62

O2N

NO2 Dioxane H rt NO2

Ph

O 64

61%

O Ph

61

Ph

O

63

NO2 NO2 NO2

93% 65

Scheme 12

O

O2N O2N

R2 NO2 R1 66

HNO3 H2SO4

NO2 O2N O2N C C NO2 NO2 O2N 67

NO2

O

HNO3 Me H SO 2 4 19%

O2N NO2

O2N

68

1 2 R = H, R = Me 1 R = H, R2 = Et 1 2 t R = H, R = Bu 1 2 R = H, R = CH2CH2CO2H 1 2 R = H, R = 3-NO2-C6H4 1 R = Me, R2 = Me

NO2 NO2 O2N NO2 O2N 69

Scheme 13

The addition of weakly nucleophilic alcohols even to unactivated alkenes was made feasible under mild reaction conditions by the simple use of BF3Et2O catalyst. The 2-(2,2,2-trinitro-ethoxy)-bicyclo[2.2.1]heptane (2-alkoxynorbornane) 72 was prepared from bicyclo[2.2.1]hept-2-ene (norbornene) 70 and 2,2,2-trinitroethanol 71 at room temperature in 31% yield (Scheme 14) <1997S1056>.

+ O2N 70

NO2 CH2Cl2 CH2OH rt, 15 min NO2 31% 71

O 72

NO2 NO2 NO2

Scheme 14

The condensation of the dialkyl aminomalonates 73 with 2,2,2-trinitroethanol 71 gave the corresponding Mannich bases, 2-(2,2,2-trinitroethylamino)malonates 74 in 70% and 82% yields, which were nitrated with HNO3–H2SO4 to give dialkyl 2-nitro-2[N-nitro-N-(2,2,2-trinitroethyl)amino]malonates 75 in 80% and 86% yields (Scheme 15) <2001ZOR207>. The treatment of acetonitrile N-oxide 76 with trinitroacetonitrile 77 afforded 3-methyl-5-trinitromethyl[1,2,4]oxadiazole 78 in 39% yield (Scheme 16) <2002ZOR1269>.

6.05.1.1.3

1-Amino-1,1-dinitroalkanes

The difluoroamines 81 were obtained in 20–70% yields from the reaction of dinitrocarbanions 79 with difluoroaminating reagent 80 (Scheme 17) <1996DOK358>. The 1,3-dicarbanion 82 generated from 1,1,3,3-tetranitropropane was also difluoroaminated by 83 to afford the geminal(difluoroamino)tetranitro compound 84 in 65% yield (Scheme 17) <1996IZV2689>.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

O2N

NO2 CH2OH + H2N NO2 71

CO2R CO2R 73

R = Me, Et

pH = 4 MeCO2Na

O2N

rt R = Me, 70% R = Et, 82%

NO2 H N

O2N

169

CO2R CO2R

74 HNO3–H2SO4 0–5 °C, 1 h

NO2 NO2 N CO2R O2N O N CO R

O2N

2

2

75

Scheme 15

+

–

Me C N O 76

NO2 NO2 1,3-Dipolar O2N O C N + O2N N O2N 39% NO2 N 77 Me 78

Scheme 16

R

NO2 Na+ + NO2 7

–

O NO2 MeCN F S NF2 R NF2 20–70% O NO2 80 81

R = CN, CONH2 NO2 NO2 O2N

–

–

Li+ Li+ 82

NO2

O + F S O NF2 O 83

MeCN CH2Cl2 65%

NO2 NO2 NF2 F2N NO2 NO2 84

Scheme 17

The photochemical reaction of TNM 51 in CH2Cl2 or MeCN with styrene (R = H), 4-methylstyrene (R = Me), 4-chlorostyrene (R = Cl), and 4-acetoxystyrene (R = OAc) 85 afforded two stereo isoxazolidines, 5-(4-R-phenyl)-2-[1-(4-R-phenyl)-2-nitro-ethoxy]-3,3-dinitroisoxazolidines 88, 3-nitro-5R-phenyl-4,5-dihydroisoxazole 2-oxides 87, and 1-(4-R-phenyl)-2-nitroethanones 86 (Scheme 18) <1998ACS751>. The selection of the olefin to form the nitronic ester 91 in the reaction with TNM 2 is a crucial factor in the synthesis of isoxazolidines (92, 94, and 96). Bicyclobutylidene 89 is the compound for this purpose. The compound 89 reacts with TNM even at 0 C; the reaction initially gives a charge transfer complex, which can be transformed into nitronic ester 91, which does not enter into 1,3dipolar cycloaddition with a second molecule of olefin 89 at low temperatures (0–5 C). Only keeping of the reaction mixture at room temperature resulted in 3,3-dinitroisoxazolidines 92 (Scheme 19) <2002DOK210>. The reaction of TNM 51 and bicyclobutylidene 89 with methylenecyclobutane 93 (R = H) or methylenecyanocyclobutane 5 (R = CN) afforded the corresponding isoxazolidines 94 in 46% and 66% yields, respectively. The olefins 95 containing electronwithdrawing groups were also reacted with 91 to yield the 3,3-dinitroisoxazolidines 96 in 24–59% yields (Scheme 19) <2002DOK210>. The aryl-O N,N-azoxy-,-dinitroalkanes 98 were prepared by nitration of the corresponding N-phenyl-N0 -(-hydroxyiminoalkyl)diazene N-oxides 97 in 60% yields (Scheme 20) <1994MI226>.

170

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) O NO2

6–27% R

86 –

O O N +

NO2 NO2 + O 2N NO2 51

R 85

NO2

CH2Cl2 4 –11%

hν

R 87

R = H, Me, Cl, OAc O2N R 18 –31%

R O

O N O 2N

NO2

88

Scheme 18

+ O 2N 89

NO2 Hexane NO2 0 °C NO2 30 min

NO2 O

O2N

51

+

N O–

1

NO2

O2N

rt 24 h

O2N O N O

91 92

91

O2N O N O

rt O2N 24 h 46–66%

+ R R = H, CN 93

NO2

94 R 1

R1 91

+

H2C

R2

95

rt O2N 24 h 24–59%

O2N O N O 96

R2

NO2 R1

2 R = H, R = CN 1 R = Me, R2 = CO2Me 1 2 R = H, R = CH(OEt)2 1 R = H, R2 = Ph R1 = H, R2 = 4-pyridyl

Scheme 19

–

O N +

N N

OH

–

i. NH4NO3–HNO3 R

ii. N2O4, ClCH2CH2Cl 60%

O N +

98

97 R = CO2Et, Me, CH2Cl, CH2N3, CH2N(NO2)Me

Scheme 20

NO2 N

R NO2

NO2

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 6.05.1.2

171

Functions Bearing Three Phosphorus Atoms

When the phosphaalkynes 99 were heated at 130 C, or at 180 C in a Schlenk pressure tube, in the absence of a solvent, complex mixtures of products were formed from which the respective tetraphosphacubanes 100 could be isolated in modest yields (8% and 2%) (Scheme 21) <1994S1337>. At higher temperatures for the cyclooligomerization, 101 were formed in 7% and 2% yields, respectively. Tetraphosphacubanes 100 could also be prepared from the zirconecene complexes 102, obtained from 103 and 99, in higher yields (50–80%) (Scheme 21) <1994S1337>.

∆

R C P

P

R

Schlenk pressure tube R = But, 180 °C, 6 h, 7% R = Pet, 200 °C, 3–5 h, 2%

P P R P R

R 101

99 ∆ Schlenk pressure tube R = But, 130 °C, 65 h, 8% R = Pet, 180 °C, 3.5 h, 2%

R

P

R R

P P

P 100

R

[2+2]-Cycloaddition 50–80% R

R R Hetero-Diels–Alders

P P

P R

P P

P

R

R

Toluene 2Cl CCCl 3 3 25 °C

R

= But,

Pet,

1-Me-Cp, 1-Me-Cy R

n

Zr Cl Cl

+ R C P

THF, Bu Li –78 °C then rt

103

Zr

P

P

R 102

Scheme 21

The treatment of t-butylphosphaalkynes with bis(cyclooctatetraene)zirconium 104 and hafnium complexes 105 afforded 106 <1995AG(E)81> and 107 <1995AG(E)2227> in 81% yield, which were then demetallated with hexachloroethane to give 1,3,5,7-tetraphosphabarrelene 108 in 88% yield (Scheme 22) <1995AG(E)81, 1995AG(E)2227>. Tetraphosphabarrelenes 110 were formed nearly quantitatively by heating a pentane solution of 2,4,6-tri-t-butyl-1,3,5-triphosphabenzene with phosphaacetylenes. Analogous reaction of triphosphabenzene with di(isopropylamino)phosphaacetylene 109 led to an unexpected product 111 in quantitative yield (Scheme 23) <1998MI2071>. The compound 109 reacted with the sterically highly substituted t-butylacetylene only at temperatures above 100 C to yield tricyclic compound 112 in 76% yield (Scheme 23) <2000S529>. The unusual reaction of t-butylphosphaalkyne with diethyl phosphite 113 at room temperature in the absence of solvent produced the primary phosphine 114 (Scheme 24) <1996ZOB522>. The phosphaalkynes undergo spirocyclotrimerization with incorporation of the corresponding Lewis acid to form the betaines 115, which was then treated with dimethyl sulfoxide (DMSO) in the presence of t-butylphosphaacetylene as a trapping reagent to afford two isomeric phosphaalkynecyclotetramers having cage structures 118 and 119 (Scheme 25) <1996CB489>. The reaction most probably proceeds by way of the triphosphabenzenes 116 and 117, which cannot be isolated as such but can only be trapped by a homo-Diels–Alder reaction. When, however, the spirocyclic zwitterion 115 was treated in the absence of a trapping reagent with an excess of DMSO at 78 C, the tetra(t-butyl)hexaphosphadecadiene 121 could be isolated in 22% yield

172

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 81%

But But P But

Zr 104

But C P

P

P

But

But

But

Cl3CCCl3

P M

88%

P

P But

P

But

P 108

R

R 106, M = Zr, R = H 107, M = Hf, R = H, SiMe3

R

R Hf R = H, SiMe3 105

Scheme 22

R R C P 25 °C, 12 h

But

P

P But

But

But

P P

P But

Pr i Pr

i

P

But

P 110

R = But, 98% R = Pent, 96%

But

109 N C P

P

–20 °C <10 min 95%

P P N Pr

But

Pr i

P

But

i

111 But

2 equiv. But

H

Toluene, –20 °C, 5 days 76%

But

But

P But P

P

112

Scheme 23

t

Bu

O Na C P + EtO P OEt 1 week H 113

H H EtO P OEt O P P O EtO But OEt 114

Scheme 24

<2002MI2622>. Compound 121 can be viewed as a dimer of the initially formed spirodiphosphete 120, which undergoes elimination of one molecule of di-t-butylacetylene. Tetracyclic compound 121 was formed more efficiently by reaction utilizing triphosphoryl metal complexes such as trimethylstannyltriphosphole 122 <1999MI3143>. The compound 118 was also prepared from the reaction of t-butylphosphaacetylene with 116 in Et2O in high yield (96%)

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

But

Cl – Cl Al Cl P But DMSO + P CH2Cl2 P But 37% But 115

C P + AlCl3

Et2O 10 min 96%

116

But

But 22%

–78 °C then rt

But

P

But P

P

P

P

But But P

117

P

P

+ But

But But P

P But

But 119

120

P

THF CrCl3(THF)3 –40 °C then rt 31%

PPP P

But

But

But

P

118

But

P P

But

P P

But But

But

+ P P 116 But C P

DMSO

118

P

173

But

But

SnMe3 P P + But P t Bu 122

121

But 116 + R2

R1

Et2O 0 °C, 0.5 h

But

But

P

P

P

R1

R2

123

1 2 R = H, R = CO2Me, 71% 1 2 R = R = CO2Me, 82% R1 = R2 = H, 85% 1 2 R = H, R = Ph, 78% R1 = R2 = Me, 88% R1 = R2 = Ph, 85% R1 = R2 = SiMe3, 80% R1 = Ph, R2 = SiMe3, 70%

Scheme 25

<1997JOM215>. [2+2+2]-Cycloaddition reaction of 116 with numerous alkynes under mild conditions afforded cycloadducts 123 in high yields (Scheme 25) <1997JOM215, 1999S1363>. The treatment of 1-stannyl-3,5-di-t-butyl-1,2,4-triphospholes 124, which could be obtained from Na[3,5-di-t-butyl-1,2,4-triphospholyl] 125 and R3SnCl, with t-butylphosphaalkyne afforded 126 in 80% yield (Scheme 26) <1999MI3143>. SnR3 P But C P P P [4+2]-cycloaddition t R = Ph 124 Bu 70 °C, 12 h

R3Sn

But

SnR3Cl –30 °C

R = Me, 98% R = Ph, 87% R = Bun, 90%

But [Na(THF)x]

But

P

But

C P [2+2+2]-cycloaddition

SnR3 But P P P P P

P But

But

P

But

P P

P

P

But But

125

126

Scheme 26

174

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

The co-condensation of electron beam generated titanium atoms with an excess of t-butylphosphaacetylene afforded the hexaphosphatitanocene complex 127. The complex 128 was formed as a result of an unusual [2+2]-cycloaddition with a P¼C bond of one of 127 (Scheme 27) <1999CC1731>. But

P

But

P

P

Ti

But

+ But

P P

But C P

P

But

But But

P

But

P

P P P Ti

P

127

P But 128

Scheme 27

The Lewis base adducts of imidovanadium(V) compound 129 underwent chemoselective cyclooligomerizatiom reactions with the phosphaalkynes to afford the corresponding azatetraphosphaquadriccyclanes 130 (Scheme 28) <2001ZN(B)951>. R1 Me N O Cl 2 1 P V N R + R2 C P Toluene R O Cl P P P Me R2 = But, Pent, 1-Ad, R2 1-Me-Cp, 1-Me-Cy 129 130 R1 = But, 1-Ad

Scheme 28 Se R1 C P + Sex Toluene Et3N 25–70 °C R1 = But, Pent, 1-Ad, 15–89%

R1

P P Se

R1

R1

R2 C P [4 + 2]

131

P P R1 P

R2

2 t t R2 C P R = Bu , Pen , 1-Ad, [2 + 2 +2]

1-Me-Cp, Mes

Se R1

P

P R1 P P

Se R2

R1 +

R2

R2

132 Toluene 150 °C, 4 days Et3P 1 2 t 82% R = R = Bu 135 11 = 3 134 P

But

P 135 But

But

But

But

P

P

P +

134

But

P

But P

But

P But

25 °C, 14 days

Scheme 29

P But P

P But P But

P P R1 P P 133

R2

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

175

The reaction of the selenodiphospholes 131, which could be obtained from the treatment of phosphaalkynes with an excess of elemental selenium in toluene in the presence of an equimolar of Et3N, with phosphaalkynes led to the formation of a pair of regioisomers 132 and 133. The removal of the selenium from the cage afforded a mixture of the tetraphosphabisprismane 135, and the valance isomeric tetraphosphasemibullvalane 134 in a ratio of 11:3 (Scheme 29) <2001HAC406>. 134 undergoes a slow and thermal isomerization leading to the bisprismane 135. Triphosphabicyclo[1.1.1]pentane 138 was obtained in 36% yield from the reaction of phosphavinyl Grignard reagent 136 with PCl3 in a 3:1 stoichiometry. This is presumably formed via the bisphosphavinyl phosphorus intermediate 137, which undergoes facile phosphavinyl coupling reaction to give the bicyclic product 138 <2002MI1209>. The analogous reaction of 136 with PCl3 in 1:1 stoichiometry afforded the bicyclic product 139 (Scheme 30) <2002MI1209>.

Cl Et 1/3 equiv. PCl3 Mg O C Et Et 2O But 36% 136 1 equiv. PCl3 Et2O 15%

P

P

Cl

P

But

But P

P But

But

P P Cl

138

137

But

P P

Cl P

P

Cl

But 139

Scheme 30

6.05.1.3

Functions Bearing Three Arsenic Atoms

There are only two reports related to this functional group since 1993. The reaction of arsaalkene 141 with the lithium salt of tri(trimethylsilyl)phosphine 142 in the presence of CoCl2 gave tetraarsanecubane 140a (M¼As) in 35% yield, which on reaction with Fe2(CO)9 in THF afforded 140b (M¼As+-Fe(CO)4) in 46% yield <1993AG86, 1993AG(E)83>. The arsacubane 140a reacts at room temperature with ethyl triflate to give the As-ethylated arsonium salt 140c. A similar reaction of 140a with benzyl triflate, generated in situ via PhCH2Cl/AgOTf, gave 140d, the As-benzylated salt of 140a. Low-temperature protonation of 140a with FSO3H/SO2 produces a mixture of arsonium ions 140e, resulting from mono- and diprotonation (Scheme 31) <1994HAC503>.

OTMS TMS As Bu

t

(TMS)2PLi

But

As

CoCl2

142

But

As

But

As But

M

As

141

But 140

140a, M = As 140b, M = As+–Fe(CO)4 140c, M = As+ –Et 140d, M = As+–CH2Ph 140e, M = As+HFSO–3

Scheme 31

176

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

6.05.1.4 6.05.1.4.1

Functions Bearing Group 15 Elements Functions bearing two nitrogen atoms and phosphorus atom

N-benzoyl- and N-methoxycarbonyltrifluoroacetamidophosphonates 145, which could be prepared from the reactions of imidoyl chlorides 143 with trialkylphosphites 144, reacted with dimethylcyanamide 146 in a [4 + 2]-cycloaddition to give 147 in 48–88% yields (Scheme 32) <2002HAC22>.

CF3 O

Et2O, rt, 2 days

Me

R1O R1O P N O 145

R2

+

N C N Me 146

5–10 °C 3h CF3 O Cl

N

O OR1 P OR1 N N

F3C

Reflux, 6 h R2 = Ph 44–88%

Me

143

O

R2

147

2 1 n i R = Ph, R = Me, Et, Pr , Pr 2 1 i R = OMe, R = Pr

R1O P OR1 OR1

+ R2

N Me

144

Scheme 32

When 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 was allowed to react with phosphorus pentafluoride in toluene, 1,3-dimesityl-4,5-dichloroimidazolium-2-pentafluorophosphate 149 was obtained in 58% yield (Scheme 33) <2000M251>.

Cl

Mes N

Cl

F F P F F F

+

N Mes 148

Mes + N F F – P F N F F Mes

Cl Toluene –198 °C

Cl

58%

149

Mes = 1-(2,4,6-mesityl)

Scheme 33

6.05.1.4.2

Functions bearing two nitrogen atoms and one arsenic atom

The reaction of the 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 with arsenic pentafluoride in 1,3-bis(trifluoromethyl)benzene furnished the 1,3-dimesityl-4,5-dichloroimidazolium-2-pentafluoroarsenate 150 in 65% yield (Scheme 34) <2000M251>.

Cl Cl

Cl

Mes N N Mes 148

+

F 1,3-(CF3)2C6H4 F As F –198 °C F F 65%

Cl

Mes + N F F – As F N F F Mes 150

Mes = 1-(2,4,6-mesityl)

Scheme 34

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 6.05.1.4.3

177

Functions bearing two nitrogen atoms and one antimony atom

The reaction of the 4,5-dichloro-1,3-dimesitylimidazol-2-ylidene 148 with antimony pentafluoride in 1,3-bis(trifluoromethyl)benzene furnished the 1,3-dimesityl-4,5-dichloroimidazolium-2-pentafluoroantimonate 151 in 75% yield (Scheme 35) <2000M251>.

Cl Cl

Mes + N F F – Sb F N F F Mes

Cl

Mes N

F 1,3-(CF3)2C6H4 F Sb F F 77% F

+

N Mes 148

Cl

151

Mes = 1-(2,4,6-mesityl)

Scheme 35

6.05.1.4.4

Functions bearing two phosphorus atoms and one nitrogen atom

The reaction of imidoyl chloride 153, which can be obtained from 152 and PCl5, with diphenyl phosphite 154 in the presence of triethylamine gave a mixture of 155 and tetraphenyl 2-fluoro-1trichloroacetamido-1,1-ethylidenebis-phosphonate 156 in 35% yield (Scheme 36) <2002JFC107>.

F

Reflux O O hexane N CCl3 6 h H PCl5 152

F Cl

Et3N Et2O

O N 153

1h O PhO P OPh H

CCl3

F PhO PhO P O

O PhO P OPh O F

O N H 155

CCl3 + PhO N P H O OPh 156

CCl3

35%

154

Scheme 36

G. Olive and co-workers prepared the tetraethyl(pyrrolidine-2,2-diyl)bisphosphonate 158 from the reaction of pyrrolidine 157, triethylphosphite, and phosphorus oxychloride in 58% yield (Scheme 37) <1998JOC9095, 2001MI275>.

O N H

OEt O + EtO P + Cl P Cl OEt Cl

157

–8 °C 1h 58%

O OEt P OEt OEt N P H O OEt 158

Scheme 37

1-Arylidineamino-1,1-diphosphonoethanes 161 were obtained by Shmarov and co-workers from the reaction of aromatic aldehydes 160 with tetrasodium salt of 1-aminoethane-1,1-diphosphonic acid 159 in 25–60% yields (Scheme 38) <2000JGU521>. The reaction of triethyl phosphite with the various types of Vilsmeier reagents 162 prepared from the N,N-disubstituted formamides, acetylamides, benzoylamides, phenylacetamides, and phosphorus oxychloride afforded the tetraethyldialkylaminomethylenediphosphanates 163 in 30–78% yields. The carbanion 164, generated from 163 by deprotonation with NaH, reacted with benzyl chloride in THF to give the C-benzylated bis-phosphanate 165 in 32% yield (Scheme 39) <1999HAC271>.

178

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) R2

O HO P OH H2N Me + HO P OH R1 O 159

O HO P OH Me N P HO OH O

O R2 H

Water–EtOH 25–60% R1

R3

R3

160a, R2 = R3 = H, R1 = OH, Et2N, NO2 1

2

161

3

160b, R = H, R = OH, R = NO2

Scheme 38

O R2 + Cl P Cl N Cl R3 162 1 R = H, Me, Ph, CH2Ph R2 = Me, Et, Pr R3 = Me, Et, Pr, Ph

O OEt P R2 1 N 3 R R P EtO OEt O EtO

O

O 2EtO P OEt + R1 H

CH2Cl2 10 h 30–78%

163 THF R1 = H NaH R2 = R3 = Me

O OEt P Me PhH2C N Me P EtO OEt O 165

O OEt P Me +– N Na Me P EtO OEt O EtO

EtO

PhCH2Cl THF 32%

164

Scheme 39

The Wittig rearrangement of the ammonium ylides 169 derived from N-allylic ammonium salts 168, prepared by quaternization of the tetraethyldimethylaminomethylene-bis-phosphanate 166, <1968AG(E)391, 1976JPR116, 1982SC415, 1999HAC271> with various allylic halides 167 resulted in the formation of tetraethyl bisphosphanates 170 in 35–85% yields (Scheme 40) <1999HAC281>. O OEt P Me H N Me P EtO OEt O EtO

166

R1 +

X

R

3

MeCN, AgBF4 reflux, 3–5 h

R2 167

X=Cl, Br, I R1 = R2 = R3 = H

O OEt R1 EtO P + Me N R3 – H BF4 Me 2 EtO P R O OEt 168

R1 = R2 = H, R3 = Me R1 = Me, R2 = R3 = H R1 = R2 = H, R3 = Ph R1 = H, R2 = R3 = Me O OEt EtO R3 P R1 Me N 2 Me R P EtO OEt O 170

[2,3]-Wittig rearrang. 35– 85%

NaH THF rt 2h

O OEt R1 + Me EtO P N EtO P Me O OEt 169

Scheme 40

R3

–

R2

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

179

[4+1]-Cycloaddition reaction of heterodienes 171 with triethyl phosphite gave the 5-phenyl-3trifluoromethyl-2,3-dihydro-25-[1,4,2]oxazaphosphol-3-yl)phosphonic acid diethyl ester derivatives 172 (Scheme 41) <1995ZOB948>. O Ph

CF3 N

Cl

+

OEt EtO P OEt

Ph

CCl4 84%

171

O OEt P OEt O P 2CF3 R1 2 R R1 = F, Cl, EtO, PhO R R2 = EtO, PhO 172 N

Scheme 41

Beckmann rearrangement of oximes 173, in the presence of phosphorus nucleophiles, e.g., dior triethyl phosphites, afforded the corresponding aminomethylene gem-diphosphanates 174 in moderate yields (30–60%). The method is applicable to the synthesis of conformationally restricted analogs. The diphosphanate 174 (R1 = Ph, R2 = Me) was converted to diphosphonic acid 175 with TMSBr in CH2Cl2 in 59% yield (Scheme 42) <1994JOC7562>. N R1

OR Beckmann R1 N C R 2

R2

+

rearrangement

173

CH2Cl2, POCl3 Pnu 30–60%

EtO OEt P O R1

N

R1

R = H, Ms OEt O Pnu phosphorus nucleophiles (Pnu) = EtO P , EtO P OEt OEt H

R1 = R2 = –(CH4)– R1 = R2 = –(CH5)– R1 = Ph, R2 = Me

R1 O OEt HN P OEt R2 P OEt O OEt

R1 = Ph, R2 = Et R1 = 4-MeO–C6H4, R2 = Me

R1 = Ph R2 = Me TMSBr, CH2Cl2 25 °C, 12 h 59%

Ph O OH HN P OH Me P OH O OH 175

174

Scheme 42

Nurgent and co-workers prepared the pyrazoline bis-phosphonates 179 and 180 from the reaction of vinylidenephosphonic acid tetraethyl ester, 177, which was obtained from the tetraethylmethylenebisphosphonate 176 and formaldehyde, with diazomethane, diazoacetate 178 (R = OEt), and diazoketones 178 (R = Ph, Et, etc.) in ether at room temperature in 30–92% yields (Scheme 43) <1993JMC134>. O O P P EtO OEt OEt OEt

O + H

H

p-TSA, MeOH NHEt2 O

176 N2CH 178 EtO O OEt P EtO O P EtO N N H 180

O R

R = OEt, Ph, Et, But, 2-F-C6H4, 3-F-C6H4, 2-Me-C6H4, 3-Me-C6H4, 4-Me-C6H4

Scheme 43

O EtO P EtO

O P OEt OEt CH2

177 R rt, 18 h Et2O

Et2O

CH2N2, 32 0 °C

EtO O OEt P EtO O P EtO N N H 179

180

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

6.05.1.4.5

Functions bearing two phosphorus atoms and one arsenic atom

Arsadiphosphabicyclo[1.1.1]pentane 182 was obtained in 41% yield from the reaction of phosphavinyl Grignard reagent 136 with AsCl3. This is presumably formed via the bisphosphavinyl phosphorus intermediate 181, which undergoes facile phosphavinyl coupling reaction to give the bicyclic product 182 (Scheme 44) <2002MI1209>.

P

Cl Et Mg O C Et But

Cl As

P

AsCl3 Et2O 41%

But

But P P

P But

But

As Cl

136

182

181

Scheme 44

6.05.1.4.6

Functions bearing two phosphorus atoms and one antimony atom

Two equivalents of the diphosphastibolyl ring anion 183 reacted with FeCl3 to produce an antimony containing cage compound 184 via an oxidative coupling mechanism (Scheme 37) The mechanism for the formation of 184 presumably involves an initial coupling reaction to give the intermediate 185, which then undergoes a [4+2]-cycloaddition reaction affording 184 <1997JCS(D)4321, 1997CC305>. The compound 184 was also obtained from the reaction of 183 with PbCl2 in 1,2-DME at 45 C (Scheme 45) <1999JCS(D)4057>.

But But

P P Sb

But

FeCl3 1,2-DME 18 h

P Sb

183

P P Sb But

But

[4 + 2]-cycloaddition

P

65%

Bu

t

P But

But

Sb P Sb

But P

P

184

But

185

Scheme 45

The reaction of 2 equiv. of 186, which could be prepared from the reaction of 188 and 189, with SiMeCl2 afforded hexahetero-cage compound 187 in moderate yield (41%) (Scheme 46) <2001JOM61>.

Me3Si

188

SiMe3 Sb + KOBut 1,2-DME –78 °C SiMe3

But –78 °C then rt P C 13% OSiMe3 189

+ Me3Si

But

Me3Si Sb K Me3Si 188

rt

P

But But

P SbH

(DME) P K P SbH

K (DME) 186

But

SiMeCl2 THF

P But

P

–78 °C then rt 41% But

P

But Sb But

P 187

Scheme 46

Me Si Me

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) 6.05.1.4.7

181

Functions bearing two antimony atoms and one phosphorus atom

The reaction of phosphavinyl Grignard reagent 136 with SbCl3 led to an unusual heterocyclic compound 190, which quantitatively decomposes in solution to yield the known 1,2-dihydro-1,2diphosphete 192. Although no intermediate was observed in this reaction, it seems likely that the phosphaalkene 191 initially forms (Scheme 47) <2002MI1209>.

Cl Cl Sb

Et Cl

O Mg

P

Et + Cl

But

Cl

Cl Et2O Sb 66% Cl

Cl Sb

P But

136

But Sb Cl

P Solution

P

P P

Cl But

But

But 190

192

191

Scheme 47

6.05.2

FUNCTIONS CONTAINING TWO GROUP 15 ELEMENTS AND ONE GROUP 13 OR 14 ELEMENTS

6.05.2.1 6.05.2.1.1

Functions Containing Two Group 15 Elements and One Group 13 Elements Functions bearing two nitrogen atoms and one boron atom

Stable imidazol-2-ylidene-borane adducts 194 were obtained from the reaction of imidazol-2ylidene 193 with Me2SBH3 or Et2OBF3 (R1 = Me and R2 = Me, Et, i-Pr) (Scheme 48) and (R1 = H, Cl and R2 = Mes) (Scheme 48) <2000M251>.

R1 N R1

N R2 193

H + – S B H Me H or Et + F – O B F Et F Me

R2 +

R1 THF or Et2O

R2 N

R1

+

N R2

X – B X X

194 X = H, F

R1 = Me, R2 = Me, Et, Pri R1 = H, R2 = Mes R1 = Cl, R2 = Mes Mes = 2,4,6-mesityl

Scheme 48

The silylation of lithium 3,5-dimethyl-1-(dimethylamino)boratabenzene 195 <1999OM5496> with chlorotrimethylsilane afforded 196 in 86% yield, which was then treated with BCl3 to give the highly reactive chloro-compound 197. When a toluene solution of imidazol-2-ylidene was added to a solution of 197 at room temperature, the adduct 198 formed immediately in high yield (80%) (Scheme 49) <2000OM3751>. The reaction of (E)-2-chlorodimethylstannyl-3-diethylboryl-2-pentene 199 <1986ZNB890>, which could be obtained via 1,1-organoboration of 1-alkynyl compounds 202, with the C-lithiated imidazoles gave a mixture of 200 and 201, which are present in the beginning as a 1:1 mixture (Scheme 50) <1995JOM197>. The borolylimidazolium salts 205 were prepared from the reactions of the appropriate 1,3-dialkyl-4,5-dimethylimidazol-2-ylidenes with 2-bromo-2,3-dihydro-1H-1,3,2-diazaboroles 204, which were synthesized by cyclocondensation reaction of the corresponding dilithiation of compounds 203 with BBr3 in hexane (Scheme 51) <1997CB705>.

182

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) Me

Me

Me

B– Li+ N Me Me 195

Me + Me Si Cl Me

Me

Me

Me

BCl3

THF 2 h, rt 86%

–

Me

B N +

SiMe3

B Cl

91%

Me

SiMe3 197

196 Me

Me N

Me

N Me

Me

Me N

Me

N Me

Toluene 83%

Me B–

+

Me

198

Scheme 49

Cl Me Sn Me Me

Et B Et

N

+

Cl Me Sn Me 202

Me N

N +

–

N Me

Et 199 Et

Me

Me Li+

Me N Sn Me

B

Me

Et

Et

–

+

Sn

B

Me Me

Et

Et Et

Et 201

200

Et B Et

+ –

N

Me

Me

Scheme 50

R3

Me N R2 N

R1 + Br

R1

N R2

B

Br Hexane Br

203 R1 = H, R2 = But

R1

R1

R2 N B N R2 Br 204

R1 = H, R2 = 2,6-Me2-C6H3

Me

N R3

R3 = Me, Pri

R1 R1

R2 N B N R2

R3 Br– + Me N N R3

Me

205

R1 = Me, R2 = Pent

Scheme 51

Treatment of 1,4,5-trimethylimidazole with triethylborane at 0 C led to 3-(triethylborane)-1,4,5trimethylimidazole 206 in quantitative yield. The treatment of 206 with n-BuLi was expected to yield a carbene 207, surprisingly the rearranged compound lithium triethyl(1,4,5-trimethylimidazolyl)borate 208 was obtained in 77% yield (Scheme 52) <1998MI843>. Methylation of 208 with MeI was carried out in THF at 30 C affording 209 in 69% yield. The reaction of 1,4,5-trimethylimidazole with BH3THF at 0 C afforded the air-sensitive compound 3-borane-1,4,5-trimethylimidazole 210, which was deprotonated with n-BuLi to give 3-borane-1,4,5-trimethylimidazol-2-ylidene 211. The reaction of 211 with chlorobis(dimethylamino)borane 212a, 2-bromo-1,3-di(t-butyl)-1,3,2-diazaboroline 212b, and triethylborane 212c led to 3-borane-2-[bis(dimethylamino)boryl]-1,4,5-trimethylimidazoline 213a

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

183

in 72% yield <1998MI843>, 2-(1-borane-3,4,5,trimethylimidazoloyl)-1,3-di(t-butyl)-1,3,2-diazaboroline 213b in 32% yield <1999MI789>, and 3-borane-1,4,5-trimethyl-2-(triethylborane)imidazoline 213c in 96% yield, respectively (Scheme 52) <1999MI789>.

Et Et

Et

Me Et 0 °C, 2 h B toluene Et 99%

N +

Me

Me

Et

N Me

N+

Me

Me Me

B

77%

N+ N Me

H H BunLi –78 °C

H

B– Li N H

Me Me

Me

+

+

N Me 208

N Me Et

Et + – Li B Et

N

Me

N Me

210

Et – N B Et Me Et

MeI, THF –30 °C, 1 h 69%

209

211 H

Me Me Me N 211 B Cl Me N Me 212a

Me

H

N Me

Me

H –

N

Me 207

BunLi –78 °C

THF H B H

Me

X

Et

N Me

206

H

B–

Et B– Et

N

Me

H

H Me H B H – N But

But

B –

H Me N N B Me Me N Me Me 213a

N B Br N But

+

211 Me

Me

+

N

B N

N

But

212b

213b

Et Et

B

H

Me 211

N Me

Et 212c

H B –

+

H Et B Et Et

N Me 213c

Scheme 52

Martinez and co-workers prepared the 1,5-dimethyl-4,4,8,8-tetrahydroimidazaboles 215a (Scheme 53) <1994CB343> and 1,5-dibenzyl-4,4,8,8-tetrahydroimidazaboles 215b (Scheme 53) <1998MI1547> from N-methylimidazole-N-borane 214a and N-benzylimidazole-N-borane 214b.

H +

–

N

B

H H

H I2,270 °C

32% N R 214a R = Me 214b R = CH2Ph

N

H B –

+

R N

– N N + B R H H

215a R = Me 215b R = CH2Ph

Scheme 53

The treatment of 1-alkynyl(chloro)dimethylsilane 216 with tetraethyldiborane or 9-borabicyclo[3.3.1]nonane dimer, (9-BBN)2, afforded the (Z)-1-chloro-dimethylsilyl-1-diethylboryl-alkenes 217 <1999JOM98> and (Z)-1-chloro(dimethyl)silyl-1-(9-borabicyclo[3.3.1]non-9-yl)-3,3-dimethylbut-1-ene 218 <2000JOM45>, respectively, which were reacted with 2-lithio-1-methylimidazole to

184

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

give 219–222. The treatment of 1 equiv. of B(C6F5)3 223 with 2-lithio-1-methylimidazole yields 224 in 63% yield (Scheme 54) <2002MI2015>. Et H Et2BH But Me Si Cl Me

But

But Me Me Si + N

N B Et

Li

N Me

Me Si Me Cl 217

But Me Me Si

H Et –

B

+ Et

Me 219, 80%

Et –B

N+ Et

Me N

N

H

221, 20%

N

216

B

H 9-BBN

But

Li

N Me

Me Si Me Cl

But Me Me Si + N

218

But Me Me Si

H B– N

+

+

Me N

F

F F

F B

N N Me

F F

Li

F

F

F

Li+ –

63% F

FF

F

F F 223

F

F B

F

B–

222, 7%

F

F F

N

Me

220, 93% F

H

FF

N Me F

F

F

N

F F

F

224

Scheme 54

6.05.2.1.2

Functions bearing two nitrogen atoms and one gallium atom

The gallium compound 227 was obtained from the reaction of complex 226 <1963IC1039>, which was prepared from lithium gallium hydride and trimethylammonium chloride, with imidazol-2-ylidene in 40% yield (Scheme 55) <1998JCS(D)3249>. The treatment of 1,3-bis(2,4,6trimethylphenyl)imidazol-2-ylidene with an equimolar amount of LiGaH4 in Et2O afforded the gallium complex 228 in 89% yield (Scheme 55) <2000OM4852>. The treatment of the potentially chelating reagent bis-carbene 1,2-ethylene-3,30 -di-t-butyl-diimidazol-2,20 -diylidene 225 with GaH3NMe3 in a 1:1 or 1:2 stoichiometry led to the 2:1 adduct 229, which is moderately thermally stable compound (Scheme 55) <2002JCS(D)1992>. The unusual reaction of 230 with 1,3,4,5-tetramethylimidazol-2-ylidene in toluene gave complex 233 in 54% yield (Scheme 56) <2002JOM487>. A possible mechanism for the formation of 233 involves the initial displacement of a [C5H5] and formation of an unstable adduct of the decamethylgallocenium cation 231, which undergoes reaction with the [C5H5] counter ion via hydride transfer to form tetramethylfulvane 232 and 233.

6.05.2.1.3

Functions bearing two nitrogen atoms and one indium atom

The reaction of imidazole-2-ylidene with InX3 (X = Cl, Br) yielded 1:1 234 or 1:2 235 complexes depending on the stoichiometry employed (Scheme 57) <1997JCS(D)4313>. Treatment to an ethereal solution of InH3NMe3, generated in situ from LiInH4 with 2 equiv. of imidazol-2-ylidene at 30 C led to a moderate yield (42%) of 236, which is an extremely air sensitive material (Scheme 57) <1998CC869, 1998JCS(D)3249>. The treatment of LiInH4 with 2 equiv. of imidazol-2-ylidenes also gave 236 in 38% yield.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) Me H Et2O + H Ga– H Li+ + Me N H Cl – –30 °C Me H 3h Et2O Mes –78 °C N rt 89%

H Me 40% – + H Ga N Me –78 °C, Et2O H Me Pri Me N 226 But N

N Mes

+

H Ga H H

–

N Pri 227

Me

N Pri

Me Et2O –50 °C

N 225

Mes H N – + Ga H N H Mes 228

Pri N

Me

185

59% N N But H – H Ga H

Mes = 2,4,6-mesityl

But N

+

N

N

N But

+

–

H Ga H H

229

Scheme 55

Me Me

Me Me Me Me Me

Me

Me Me Me Ga Me Me Me

Me Me

Me + Me

Me N Toluene –78 °C N Me

Me

Me Me Me

rt 54%

Me Me

Me Me Me

Me

–

Me

N Me Me

Me

230

Me

Me Me N Ga +

Me

231

Me Me

Me Me

+ Me

Me

Me

Me Me Me 232 Me

–

Me Me N

Ga H Me

Me

+

Me

N Me Me

233

Scheme 56

Treatment of an ethereal solution of either LiInH4 or InH3NMe3 with 1 equiv. of the 1,3dimesitylimidazol-2-ylidene 237 at 78 C resulted in the formation of indium trihydride complex 238 in high yield (Scheme 58) <2000OM4852>. Compound 238 displays a remarkable thermal stability. In solution the products of decomposition depends on the solvent used. In toluene decomposition results in liberation of the free carbene and deposition of indium metal, in CH2Cl2, chloride abstraction occurs from the solvent to yield 240. The reaction of InH2ClNMe3 with an equimolar amount of 237 afforded 239 in 65% yield. The reaction of 0.5 or 1 equiv. of the 1,3dimesitylimidazol-2-ylidene 237 with InBr in toluene at 25 C led to the deposition of indium metal

186

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

and formation of the thermally robust carbene–indium complex 241 in 54% yield (Scheme 58) <2002CC1196>. The treatment of 1,3-dimesitylimidazol-2-yliden 237 with InBr3 and Et2O with carefully resublimed InBr3 afforded 1:1 adduct 242 in 88% yield (Scheme 58) <2002JOM203>.

1:1 X X In X

Pri X N – + In X N X Pri

Me Me

THF 20 °C 3h

X = Cl 74% X = Br 43% 234

1:2 X

Me

Pri N

Me

N Pri

X In X

Pri Me Pri N X N + + In Me N N X X i Pr Pri

Me Me

THF 20 °C 3h H Me – + H In N Me H Me –30 °C 2 h, 42% H – H In H H Et2O –30 °C 5 h, 38%

X = Cl, 38% X = Br, 69% 235 Me Me

Pri H N – + In H N H Pri 236

Scheme 57

Mes LiInH4 Mes Mes Mes + InBr H N Br Br N 86% N N – toluene – – + In H + In In N 25 °C H N N N Br Br InH3NMe3 54% Mes Mes Mes Mes 238 54% 237 241 Et2O InH2ClNM3 CH2Cl2 –50 °C, then rt InBr3 65% Et2O 67% 2h –50 °C 88% Mes + Mes Mes Br N – + + Cl N – H N In Br – In Cl In Cl N Br N N H Cl Mes Mes Mes 242 239 240

Scheme 58

Treatment of bis-carbene, 1,2-ethylene-3,30 -di-t-butyldiimidazol-2,20 -diylidene 225, with LiInH4 or InH3NMe3 in a 1:1 or 1:2 stoichiometry led to good yields of the indium-rich 2:1 adduct 243. In contrast, the 1:1 or 1:2 reaction of 243 with InBr3 yielded the 1:1 adduct 244 in 41% yield (Scheme 59) <2002JCS(D)1992>.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

187

Et2O, –50 °C, 48%

But N 225

N

N

N But

But N

+

N

N

N But

+

H In H

Et2O, –78 °C, 58% H H In– H Li+ H 2 equiv.

N

+

But

H – H In H

–

InBr3 –78 °C then rt THF 41% Br N In + N Br Br N

H Me – + H In N Me H Me

H

243

But

244

Scheme 59

6.05.2.1.4

Functions bearing two nitrogen atoms and one thallium atom

Treatment of bis-carbene, 1,2-ethylene-3,30 -di-t-butyl-diimidazol-2,20 -diylidene 225, with 2 equiv. of TlCl3 in THF yielded the 1:1 adduct 245 in 92% yield (Scheme 60) <2002JCS(D)1992>.

But N

N

N

Cl N But + Tl 2 Cl Cl

225

Cl N Tl + N Cl Cl N N

THF –78 °C then rt 92%

+

But

But

245

Scheme 60

6.05.2.1.5

Functions two phosphorus atoms and one gallium atom

Phosphaalkyne (R = t-Bu) underwent spirocyclotrimerization structure 246 in high yield (95%) (Scheme 61) <1996CB489>. with 3 equiv. of phosphaalkyne (R = t-Bu and 1-Ad) in Et2O in moderate yield (43–49%) (Scheme 61) <1998MI1597>. coordinated at a phosphorus atom of the polycyclic system. Cl Cl Ga Cl CH2Cl2 95%

R C P

Et Et Ga Et Et2O 48 h, rt

with GaCl3 to form the betaine When triethylgallium was reacted at room temperature yielded 247 Exocyclic triethylgallium unit is

R P R

P+

246 R = But Et – Ga Et Et + P Et R Et +P – R Ga P Et R 247 R = But R = 1-Ad

Scheme 61

Cl Cl Ga – Cl

49% 43%

188

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

Lithiation of 248 with 1 equiv. of n-butyllithium in THF gave the monolithium salt of the product 249 in 78% yield, which was then reacted with GaCl3 to furnish the compound 250 in 68% yield (Scheme 62) <1999JA2939>. Me Ph Ph Me Si N P Me Ph P Me Ph N Si Me Me 248

Bun THF 78%

Me Ph Li+ Me Si N P – Ph Me Ph P Me Ph N Si Me Me Cl 249 Ga Cl Cl Benzene 68%

Cl Ph Ga Cl Me Si N P Ph Ph P Me Me Ph N Si Me Me 250 Me

Scheme 62

The reaction of 3 equiv. of 136 with gallium(III) chloride in toluene led to the formation of diphosphagalliumbicyclo[1.1.1]pentane complex 253 in low yield (15%) (Scheme 63) <2001JOM109>. The mechanism of this reaction is not determined as the reaction proceeds too rapidly to observe any intermediate by 31P-NMR spectroscopy. However, it is believed that the gallium chloride initially reacts with 2 equiv. of 136 to give the intermediate 251, which then undergoes intramolecular phosphavinyl coupling reaction to afford 252, which reacts with a third equivalent of 136 to yield 253.

Cl Ga

But P

P

But But

P

Ga Cl But

251

P 252

Cl

Cl Ga

Toluene 136 15%

Cl

But P

Cl Mg Et O Et

P But

Ga But

3 equiv. 136

P

P But

253

Scheme 63

6.05.2.1.6

Functions bearing two phosphorus atoms and one indium atom

The reaction of 3 equiv. of 136 with indium(III) chloride in toluene led to the formation of diphosphaindiumbicyclo[1.1.1]pentane complex 256 in (42%) yield (Scheme 64) <2001JOM109>. The mechanism of this reaction is not determined as the reaction proceeds too rapidly to observe any intermediate by 31P-NMR spectroscopy. However, it is believed that the indium chloride initially reacts with 2 equiv. of 136 to give the intermediate 254, which then

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

189

undergoes intramolecular phosphavinyl coupling reaction to afford 255, which reacts with a third equivalent of 136 to yield 256.

Cl In

But

P

But

P

But

P 254

Cl

Cl In

In

Cl

But P Toluene

255

136

42%

Cl

But P

Cl Mg Et O Et

P But

In But P

3 equiv. 136

P But

256

Scheme 64

6.05.2.1.7

Functions bearing one phosphorus, one nitrogen, and one boron atom

The reaction of 257 with BF3OEt2 or BH3THF afforded 258, which was then treated with ,-unsaturated esters to yield pyrazolines 259 (Scheme 65) <1991AG(E)1154>.

Pri

Pri

N + – Cl P C N N N Pri Pri 257

BF3OEt2 or BH3THF

Pri i + N Pr N N Cl P C – Pri N B X X Pri X 258

Pri

O Cl

OMe R R = H, CO2Me

X = H, F

Pri

N P +

Pri N N

CO2Me N – Pri X B X R X X=F 259

Scheme 65

6.05.2.2 6.05.2.2.1

Functions Containing Two Group 15 Elements and One Group 14 Element Functions bearing two nitrogen atoms and one silicon atom

Photolysis of a benzene solution of (1-methyl-2,3,4,5-tetraphenyl-1-silacyclopentadienyl) diazomethane 260 in an excess of methanol yielded (1-methyl-2,3,4,5-tetraphenyl-1-silacyclopentadienyl)diazirine 261 and other side products 262–264 (Scheme 66) <1985OM584>.

6.05.2.2.2

Functions bearing two nitrogen atoms and one germanium atom

Triphenylgermyl-bis(3,5-dimethylpyrazol-1-yl)methane 267 could be prepared by the reaction of bis(3,5-dimethylpyrazol-1-yl)methyllithium 266, which was generated from 265 and n-BuLi in THF, with triphenylgermanium bromide in moderate yield (48%) (Scheme 67) <2002JOM198>. The treatment of 267 with W(CO)5THF prepared in situ afforded complex 268 in 43% yield.

190

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) Ph

Ph Ph

Ph

Si

CHN2

Me

Ph

Ph hν Benzene MeOH

Ph

Ph +

Si Me N

260

Ph

Ph

+ Ph

Si Me

19% 262

48% 261

Ph

Ph

+

OMe

Et

N

Ph Ph

Si

Ph

Ph

Ph

Ph

Ph OMe

Si Me

7% 263

OMe

8% 264

Scheme 66

Me

Me N N

N N

N N

–78 °C, 1 h Me

Me

Me

Me BunLi

–

Li+ 266

Me

265

N N Me

Ph THF Ph Ge Br 48% Ph OC CO Me OC W CO N N N N

Me

Me

Me

Me N N

W(CO)5THF 43%

Me Ge Ph Ph Ph 268

Me Ph

N N Me Ge Ph Ph 267

Scheme 67

6.05.2.2.3

Functions bearing two phosphorus atoms and one silicon atom

The reaction of 2 equiv. of t-butylphosphaalkyne with silene 270, which was obtained thermally from the disilacyclobutane 269 by [2+2]-cycloreversion, afforded diphosphatricyclobenzoheptane 271 in 75% yield (Scheme 68) <1994JOM41>.

Me3Si SiMe3 Me3Si Si Si SiMe3 Me3SiO

∆

OSiMe3

Me3Si Si Me3Si

Ph Ph

OSiMe3 Ph

Toluene But C P 75%

Me3Si Me3SiO Si Me3Si P

270

269

But

P But 271

Scheme 68

Hydrostannylation of phosphaalkene 272 with tributyltin hydride in pentane or petroleum ether gave 1,3-diphosphacyclobutane 273 in low yield (7%) (Scheme 69) <1998HAC453>.

SiMe3 Cl

P C Ph 272

+

Bu3SnH

Petroleum ether 20 °C, 1 days 7%

Scheme 69

Me3Si Ph

H P

Ph

P SiMe3 H 273

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

191

1,3-Diphosphacyclobutane-2,4-diyl 275, which can be obtained from 1,3-diphosphacyclobutane2,4-diyl 274 by selective Cl/SiMe3 exchange, can be transformed into the protonated form 276 with n-BuLi and subsequent t-BuOH addition. Where 276 is thermally stable, irradiation induced a rapid conversion of 276 into the 1,3-diphosphabicyclo[1.1.0]butane 277, which can be transformed into the 1,4-diphosphabutadiene 278 in 68% yield by heating 277 (Scheme 70) <1999AG(E)3028>. Cl Mes P

Cl Hg(SiMe3)2

P Mes

Mes P

H P Mes

71% Cl 274

SiMe3

BunLi

Mes P

ButOH 97%

276

P Mes SiMe3

275 hν 90%

Mes = 2,4,6-Bu3t C6H2 H Me3Si 278

Mes P P Mes

H ∆ 68%

Mes P 277

P Mes SiMe3

Scheme 70

The reaction of trimethylsilylphosphaacetylene, which can be prepared from dichloro(trimethylsilyl)methylphosphane 279 in 70% yield <1991AG(E)196>, with an excess of the buta-1,3-dienes (R=H, Me) produced in a 2:1 stoichiometry the phosphatricyclooctenes 282 in 50–55% yields (Scheme 71) <1999MI363>. The Diels–Alder adduct 280 as well as the product 281 of a phosphaene reaction are assumed to be formed as intermediates prior to the intramolecular [4+2]cycloaddition leading to the polycyclic product 282. R Cl Cl

TMS

350 °C

P H

TMS C P

H R

R [4 + 2] rt, 2 h R = H, Me

H 279

TMS P

R

280 TMS C P ene reaction

R

TMS

R R

P P TMS

[4 + 2] Intramolecular 50–55%

282

R

TMS P H

TMS

281

Scheme 71

The stable bis(amino)silylenes 283 underwent smooth [1+4]-cycloaddition with 2,4,6-tri-tbutyl-1,3,5-triphosphabenzene 284 to furnish 285 in 66% and 80% yields, respectively (Scheme 72) <2002JCS(D)484>.

6.05.2.2.4

Functions bearing two phosphorus atoms and one germanium atom

The compound 287 was prepared in high yield (80%) from the reaction of 286 with 1 equiv. of GeCl2. The compound 287 was then treated with carbanion 289 to yield 288 in 75% yield (Scheme 73) <1999OM389>.

192

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) [NN] t

P

Bu [NNSi]

+

Si

But

But

Benzene P

283

P

66–80%

P

P t Bu

But 284

285 But

CH2But N and Si N CH2But

[NNSi] =

But

P

N Si N But

Scheme 72

Li+

Ph – HC P Ph P Ph Ph Et2O 75%

289 N Me3Si

SiMe3

Ge

Me3Si

SiMe3

N

Et2O GeCl2 dioxane 80%

SiMe3 N Ge Cl

SiMe3

287

SiMe3 N Ge Ph

SiMe3

Ph P P Ph Ph 288

286

Scheme 73

The metallation of bis(iminophosphorano)methane 290 with n-BuLi in THF gave the monolithium salt 291, which was then reacted with 0.5 equiv. of GeCl2 to produce bis(germavinylidene) 292 in 42% yield (Scheme 74) <2001AG(E)2501>. The reaction of 292 with W(CO)5 and Cr(CO)5 in THF afforded 293 in moderate yields (37% and 43%) (Scheme 74) <2003CC248>.

Ph Ph P N SiMe 3 Ph P N SiMe3 Ph 290

THF n-BuLi

Ph Ph Ph N SiMe3 N P P 1/2 equiv. GeCl2 Me3Si Ph N Ge Li+ – Ge Et2O, dioxane P N SiMe 3 Ph Ph P 42% Ph P Ph Ph 291 Ph N SiMe3 292 M(CO)5THF M(CO)5 M = W, 37% Me3Si N Ge M(CO) M = Cr, 43% 3 Ph P Ph Ph P N SiMe 3 Ph 293 Ph Ph P N SiMe 3

Me3Si

Scheme 74

6.05.2.2.5

Functions bearing two phosphorus atoms and one tin atom

Reactions of the tin hydrides with an excess of the phosphaalkynes at room temperature for 2 weeks gave the 2-stannyl-substituted 1,2-dihydro-1,3-diphosphetes 294 in 22–74% yields depending on substituents. Reactions of the phosphaalkyne (R = But) with chlorodiorganotin hydrides proceed much less selectively than those with the triorganotin hydrides. In addition to the

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

193

1,2-dihydro-1,3-diphosphetes 295 formed as main product with the yield (85%), numerous side products were formed (Scheme 75) <1998MI235>.

R13SnH

+ R2 C P

R1 = n-Bu, Ph

R2 C P H R13 Sn

n-Pentane 2 weeks

R2 = t-Bu, t-Pent, 1-Ad

R12ClSnH + R2 R1 = n-Pr, n-Bu

n-Pentane C P 2 weeks

R2 C P H R12ClSn

R2 C P

R2

[2 + 2]-cycloaddition 22–74%

R2 C P [2 + 2]-cycloaddition

294

R2

85%

R2 = But

SnR13 P P

R2

SnClR12 P P R2 295

Scheme 75

6.05.2.2.6

Functions bearing two antimony atoms and one silicon atom

The chloro-bridged polymeric C-centered geminal distibine 298 was obtained in 63% yield by the thermolysis of the doubly bonded intermediate species 297, which could be prepared from 296 and SbCl3 (Scheme 76) <1998CC575>.

THF –78 °C then rt 3 days

N

Me N

Me

SiMe3 Cl Li SiMe + Cl Sb 3 N Me Cl Me 296

N 297

SiMe3 Cl 63%

Cl

Toluene 50 °C 4h

Cl Sb

SiMe3

Et2O

N

–78 °C

SiMe3

N

Me3Si

Cl Sb SiMe3 Cl

Sb

Cl

N

298

Scheme 76

6.05.2.2.7

Functions bearing one nitrogen atom, one phosphorus atom, and one silicon atom

[1+2]-Cycloaddition reaction of [bis(dicyclohexylamino)phosphino]trimethylsilylcarbene 299 with benzonitrile in toluene afforded 2-phosphino-2H-azirine 300 in 85% yield (Scheme 77) <1995AG(E)1246, 1997MI1757>.

N

SiMe3 P

N

+ Ph C N

Toluene 85%

Ph

N

N P

N

Me3Si

300 299

Scheme 77

194

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

6.05.2.2.8

Functions bearing one phosphorus atom, one antimony atom, and one silicon atom

See compound 187 in Scheme 46 in Section 6.05.1.4.6.

6.05.3 6.05.3.1

FUNCTIONS CONTAINING ONLY ONE GROUP 15 ELEMENT Functions Bearing One Nitrogen Atom and Two Silicon Atoms

The functionalization of imines 302, which were prepared from the reactions of bis(trimethylsilyl)methylamine (BSMA) 301 and aldehydes, with electrophilic reagents through the formation of an intermediate 2-azaallylmetallic derivative 303 by hydrogen–metal exchange was carried out by A. Ricci and co-workers (Scheme 78) <1994SL955>. A very good control of the regioselectivity occurs in the deprotonation of imino derivatives of 301 followed by quenching with electrophiles. Functionalization at C-1 or C-3 takes place selectively depending on the nature of electrophile and base used (304 and 305).

Me3Si Me3Si

O NH2 +

R

301

Mol. sieve H benzene 0 °C then rt

Me3Si

R N

Me3Si

Base H THF

302

R = Ph, Me3Si–CH=CH, Et–CH=CH Me3Si E Me3Si

R H 304

R = Ph Base = MeLi E+ = MeI 63% yield

M+ – Me3Si

R N H

303 Me3Si

+

N

Me3Si

R N

Me3Si

E H

E+

Me3Si

R N

Me3Si

–

M+

H

305 R = Ph Base = MeLi E+ = Me3SiCl 60% yield

Scheme 78

Bis(trimethylsilyl)methyl-isocyanate 309 and bis(trimethylsilyl)methyl-isothiocyanate 310 were obtained from the reactions of [[bis(trimethylsilyl)methyl]imino]triphenylphosphorane 308, which was prepared from bis(trimethylsilyl)methyl azide 307 generated from bis(trimethylsilyl)methyl chloride 306, with PPh3 in 81% and 83% yields, respectively (Scheme 79) <1995JOC6032>. The symmetrically substituted bis(trimethylsilyl)methyl carbodiimide 311 could be prepared in 76% yield via a Wittig-type reaction of 308 with 309. The synthesis of the unsymmetrically substituted carbodiimide 312 was performed by using two different procedures. The compound 312 was obtained in a 2.5:1 mixture with the symmetrically substituted N,N0 -diphenylcarbodiimide 313 from the reaction of 308 with phenyl isocyanate or by the reaction of N-phenyltriphenylphosphinimine 314 with 309 in 82% yield (Scheme 79) <1995JOC6032>. [Bis(trimethylsilyl)methyl]sulfinylamine 315 was prepared by the reaction of BSMA with thionyl chloride in 65% yield. Mono- and bis(trimethylsilyl)benzyl isothiocyanates 316 and 317 were synthesized via lithiated benzyl isothiocyanates and chlorotrimethylsilane in 88% and 91% yields, respectively (Scheme 80) <1997MI232>. The reaction of N-BOC-2-trimethylsilylpyrrolidine 318 with chlorotrimethylsilane in the presence of TMEDA afforded a mixture of N-BOC-2,2-bis(trimethylsilyl)pyrrolidine 319 and NBOC-2,5-bis(trimethylsilyl)pyrrolidine 320 in 71% yield (Scheme 81) <2001MI1061>. The use of HMPA in place of TMEDA resulted in the formation of completely regioselective product 320 in 87% yield (Scheme 81) <2002JA14824>. The transient silenes 322, which are strongly influenced by reverse Si¼C bond polarization, were formed upon heating of tris(trimethylsilyl)silylamides 321. The silenes were trapped with

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

Me3Si Cl

NaN3

Me3Si N3 Me3Si

Me3Si

307

306

PPh3 THF 25 °C 2h

Me3Si N PPh3

Me3Si CO2 Et2O 81% Me3Si 25 °C 5 min

+

308

N C O 309

Me3Si 308

CS2 Me3Si 83% Me3Si

308

195

Me3Si

+ 309 Benzene reflux 1h 76%

N C S 310

SiMe3 N C N SiMe3 311

Me3Si

Benzene Me3Si Ph N C O N C N Ph Ph N C N Ph Ph N C O reflux Si Me 3 3h 312 313 56% 82% 309 312:313 = 2.5:1 Ph Ph N P Ph Ph 314 Me3Si NH2 +

SOCl2

Me3Si

Et2O

Me3Si

Et3N 65%

Me3Si

N S O 315

Scheme 79

1 equiv. Me3SiCl PhH2C N C S

LDA, Et2O–hexane

88% 2 equiv. Me3SiCl 91%

Ph Me3Si 316

N C S H Ph

Me3Si 317

N C S SiMe3

Scheme 80

i. BusLi, Et2O, TMEDA COOBut

Me3Si

ii. Me3SiCl, 71%

N SiMe3 318

COOBut N SiMe3

+

319 i. BusLi, Et2O, HMPA

COOBut N SiMe3 SiMe3 320

320

ii. Me3SiCl, 87%

Scheme 81

2,3-dimethyl-1,3-butadiene to afford a quantitative yield of only one of the possible diastereomers of the functionalized cyclic allyl silanes 323 (Scheme 82) <2002MI1915>.

6.05.3.2

Functions Bearing One Phosphorus Atom and Two Silicon Atoms

The P-metallophosphiranes 325 could be prepared from the reaction of 324 <1986OM593> with aryl isocyanides in moderate yields (56–69%) (Scheme 83) <1993OM4653>.

196

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) +

O ∆ TMS R1 Si N benzene 2 TMS TMS R

TMS

O

–

Si TMS

TMS N R2

O

R1

TMS

–

Si TMS

TMS +

N R2

R1

322

321

Me

Me

Me

Me

1 = R2 = Ph,

97% R R1 = R2 = Me, 88% R1 = Me, R2 = Ph, 95%

TMS Si TMSO

NR1R2 TMS

323

Scheme 82

+ Ar

+

–

N C

OC

P SiMe3 Fe C OC SiMe3 324

Benzene

SiMe3

20 °C, 2 h

OC Fe P CO

SiMe3

Ar = Ph, 56% Ar = 2-MeC6H4, 67% Ar = 2,6-(Me)2C6H3, 69%

N Ar

325

Scheme 83

The reaction of P-chloro-bis(trimethylsilyl)methylenephosphane 326 with diisopropyl(trichlorosilyl)phosphane 327 afforded 1-bis(trimethyl)methylidene-2,2-diisopropyldiphosphane 328 in 82% yield (Scheme 84) <1998ZAAC1447>. The P¼C double bond in 328 could be protected reversibly by a [2+4]-cycloaddition with cyclopentadiene resulting in the formation of a P-phosphanyl phosphannorbornene 329, with 2,3-dimethylbutadiene produced the cyclic diphosphane 330, and with selenium gave 331 which was then treated with cyclopentadiene to furnish 332.

Me3Si P Cl Me3Si

+

Pri P SiCl3 Pri

326 Pentane 20 °C 74%

328 +

+

Me3Si

82%

Me3Si

Me3Si

Pri Me

Pri

328 +

SiMe3 329

Se Me3Si

+ SiCl4 Pri

328 Pri

P P

Pri P P

327

Me3Si 328

CH2Cl2

Me 91%

Me

Se P Se P Pri Pri 331

70%

Me3Si

Me

P Pri SiMe3

SiMe3 330

Se i P Se P Pr i Pr SiMe3 332

Scheme 84

P

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

197

The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O or THF gave 334, which was then treated with PCl3 at 78 C in Et2O to give the [6-methyl-2bis(trimethylsilyl)methylpyridine]-phosphorus dichloride 335 in 66% yield (Scheme 85) <2000JOM213>. The reaction of 335 with LiAlH4 in THF afforded 336 in 42% yield <2000CC1961>. When the reaction was carried out in Et2O, the compound 337 was obtained and not the expected dihydride species <1998CC547>. As seen in Scheme 85, the choice of solvent is crucial.

Me

N

SiMe3 SiMe3

Li+

BunLi THF, 0 °C

Me

–

N

SiMe3

SiMe3

333

PCl3, Et2O –78 °C, 6 h 66%

SiMe3 Me

N

SiMe3

P Cl

334

Cl 335

THF

Me3Si

–78 °C

SiMe3 Me P H H Al N Al N H H P Me Me3Si

335 + LiAlH4

SiMe3

336

Et2O –78 °C

Me

Me3Si SiMe 3 H N P P N H Me3Si SiMe3

Me

337

Scheme 85

The LiBr-phosphoranylidine carbenoid 339 was obtained by treatment of dibromo species 338 <1999JA5953> with 1 equiv. of n-BuLi at 78 C. In typical carbanion fashion, 339 reacted with water to give the bis(methylene)phosphorane 341 (Scheme 86) <2002OM4919>. The reaction of the dibromo compound 338 with 2 equiv. of n-BuLi afforded 340, which was then quenched with water or MeI to furnish the product 342 in 96% yield. The dimethylated bis(methylene)phosphorane 342b was not stable and rearranged within days to form vinyl-substituted phosphane 343 in 69% yield (Scheme 86) <2002OM4919>.

6.05.3.3

Functions Bearing One Arsenic Atom and Two Silicon Atoms

The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O or THF gave 334, which was then treated with AsCl3 at 78 C in Et2O to give the [6-methyl-2bis(trimethylsilyl)methylpyridine]-arsenic dichloride 344 in 68% yield (Scheme 87) <2000JOM213>. The reaction of 344 with LiAlH4 in THF afforded 345 in 35% yield. When the reaction was carried out in Et2O, the dihydride species 346 was obtained in 60% yield <2000CC1961>.

6.05.3.4

Functions Bearing One Antimony Atom and Two Silicon Atoms

The monochloride species 347 was obtained from the 2:1 reaction of 296 with SbCl3. The compound 347 is not stable and Me3SiCl elimination at room temperature occurs giving 348,

198

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

which was then reacted with AlMe3 in THF to afford 349 in 32% yield (Scheme 88) <1997CC1183>, with Et3In in hexane at 78 C to give 350 in 63% yield <1999OM4247>, and with Me3Ga either in THF–hexane at 78 C to produce 351 in 73% yield <2000OM1277> or in hexane at room temperature to furnish 352 in 34% yield, which was also prepared by warming a hexane–toluene solution of 351 to 60 C for 4 h and allowing it to cool to room temperature, followed by refrigeration at 4 C <2000OM1277>.

SiMe3 Me3Si

1 equiv. BuLi

P

SiMe3

Br 2 equiv. BuLi

Me3Si

338

Li P

Mes

Li

340

SiMe3 Me3Si

CH2 P

Mes

Me3Si

Me 343

Br P

97%

Li Mes 339

Br

Mes

H 2O

P

Bus Me3Si

SiMe3

Br

H Mes 341

SiMe3 H2O or R Me3Si MeI P 96% R Mes 342a R = H 342b R = Me Pentane 4 weeks –25 °C R = Me 69%

Scheme 86

Me

N 333

SiMe3

BunLi THF, 0 °C

Li+ Me

N

SiMe3

334

THF –78 °C 35%

–

–78 °C, 6 h 68%

SiMe3

SiMe3 Me As H H Al N Al N H H As Me Me3Si 345

Me3Si

344 + LiAlH4 Et2O –78 °C 60%

AsCl3, Et2O

SiMe3

SiMe3 Me

N Cl

SiMe3 As Cl 344

SiMe3

SiMe3 Me

N

SiMe3 As

H

H 346

Scheme 87

The deprotonation of 6-methyl-2-bis(trimethylsilyl)methylpyridine 333 with n-BuLi in Et2O or THF gave 334, which was then treated with SbCl3 at 78 C in Et2O to give the [6-methyl-2bis(trimethylsilyl)methylpyridine]antimony dichloride 353 in 74% yield. When the reaction was run in THF at 78 C, 354 was obtained in 58% yield (Scheme 89) <2000JOM213>.

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

N Me Li Me N

–

SiMe3

SiMe3

+

N Me Me

Cl Sb

Cl

SiMe3 SiMe3

N Et2O

Cl Sb

Cl –78 °C

Me3Si

Me3Si 348

+ 2.5 equiv. AlMe3

THF –78 °C

Sb

SiMe3

Me3Si

Me

N

348

SiMe3

N Sb

32%

SiMe3 SiMe3

N

347

296

N

199

Me N

Al SiMe3 Me 349

SiMe3 SiMe3 Sb Et SiMe3

N

+

348

Et3In

Hexane –78 °C

Et

63%

In

Et

N 350 Me3Si

+ 1.5 equiv. Me3Ga.THF

348

THF–Hexane –78 °C

SiMe3

N Sb

73% 351

Me N

Me Ga SiMe3 Me

Hexane Toluene 60 °C 4h

N Me Si Ga Me Me3Si Sb Me

348

+

Me3Ga.THF

Hexane rt

N

SiMe3

Me 352

Scheme 88

6.05.3.5

Functions Bearing One Bismuth Atom and Two Silicon Atoms

The treatment of a THF solution of 1-aza-allyllithium salt 355 <1999OM2256> with BiBr3 in toluene afforded the mono(1-aza-allyl)bismuth dibromide 356 in 69% yield, which is not stable in solution, and slowly decomposes even under inert atmosphere (Scheme 90) <2000POL471>.

6.05.3.6

Functions Bearing One Antimony Atom, One Gallium Atom, and One Silicon Atom

See compounds 351 and 352 in Scheme 88 in Section 6.05.3.4.

200

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

SiMe3

N

Me

+ SbCl3

+ SbCl3

334

Me

N

SiMe3

333

334

Li+

BunLi THF, 0 °C

–

SiMe3

334 SiMe3

SbCl3, Et2O –78 °C, 6 h 74%

SiMe3 Me

SbCl3, THF –78 °C, 6 h 58%

N Cl Sb Cl 353 SiMe3

SiMe3

Me Cl

N

Cl Sb N Cl Cl Sb

Me SiMe3 354

Scheme 89

SiMe3 N

Ph –

Me3Si

SiMe3

Ph

Br THF–toluene + Bi Li+ –78 °C then rt Br Br SiMe3 20 h

355

N

Me3Si Me3Si

Bi Br Br

356

Scheme 90

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202

Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

1999MI3143 1999OM389

A. Elvers, F. W. Heinemann, B. Wrackmeyer, U. Zenneck, Chem. Eur. J. 1999, 5, 3143. S. Benet, C. J. Cardin, D. J. Cardin, S. P. Constantine, P. Heath, H. Rashid, S. Teixeira, J. H. Thorpe, A. K. Todd, Organometallics 1999, 18, 389–398. 1999OM4247 P. C. Andrews, P. J. Nichols, C. L. Raston, B. A. Roberts, Organometallics 1999, 18, 4247. 1999OM5496 G. E. Herberich, U. Englert, A. Fischer, J. Ni, A. Schmitz, Organometallics 1999, 18, 5496–5501. 1999S1363 P. Binger, K. Gunther, M. Regitz, Synthesis 1999, 8, 1363–1367. 2000CC1961 P. C. Andrews, C. L. Raston, B. A. Roberts, J. Chem. Soc., Chem. Commun. 2000, 1961–1962. 2000JFC159 A. A. Kolomeitsev, G. Bissky, P. Kirsch, G.-V. Ro¨schenthale, J. Fluorine Chem. 2000, 103, 159–161. 2000JFC263 K. W. Chi, G. G. Furin, I. Y. Bagryanskay, Y. V. Gatilov, J. Fluorine Chem. 2000, 104, 263–271. 2000JGU521 A. A. Shmarov, V. I. Krutikov, T. O. Travkina, S. V. Sivukhin, J. Gen. Chem. USSR 2000, 70, 521–523 (Chem. Abstr. 134, 222781). 2000JOM45 B. Wrackmeyer, H. Maisel, W. Milius, A. Badshah, E. Molla, A. Mottalib, J. Organomet. Chem. 2000, 602, 45–50. 2000JOM120 D. L. Regel, T. C. Grattan, K. J. Brown, C. A. Little, J. J. S. Lamba, A. L. Rheingold, R. D. Sommer, J. Organomet. Chem. 2000, 607, 120–128. 2000JOM213 T. R. Ancker, P. C. Andrews, S. J. King, J. E. McGrady, C. L. Raston, B. A. Roberts, B. W. Skelton, A. H. White, J. Organomet. Chem. 2000, 607, 213–221. 2000M251 A. J. Arduengo, IIIF. Davidson, R. Krafczyk, W. J. Marshall, R. Schmutzler, Monatsh. Chem. 2000, 131, 251–265. 2000MI2105 H. Tietz, O. Rademacher, G. Zahn, Eur. J. Org. Chem. 2000, 2105–2112. 2000OM1277 P. C. Andrews, P. J. Nichols, Organometallics 2000, 19, 1277–1281. 2000OM3751 X. Zheng, G. E. Herberich, Organometallics 2000, 19, 3751–3753. 2000OM4852 C. D. Abernethy, M. L. Cole, C. Jones, Organometallics 2000, 19, 4852–4857. 2000POL471 C. Cui, H. Hao, M. Noltemeyer, H. G. Schmidt, H. W. Roesky, Polyhedron 2000, 19, 471–474. 2000S529 P. Christoph, S. Stutzmann, H. Disteldorf, S. Werner, U. Bergstra¨ßer, C. Kruger, P. Binger, M. Regitz, Synthesis 2000, 529–536. 2001AG(E)2501 W. P. Leung, Z. X. Wang, H. W. Li, T. C. W. Mak, Angew. Chem., Int., Ed. Engl. 2001, 40, 2501–2503. 2001HAC406 S. M. F. Asmus, G. Seeber, U. Bergstra¨ßer, M. Regitz, Heteroatom Chem. 2001, 12, 406–413. 2001JOC8528 J. Valenciano, E. S. Pavo´n, A. M. Cuadro, J. J. Vaquero, J. A. Builla, J. Org. Chem. 2001, 66, 8528–8536. 2001JOM61 C. Jones, R. C. Thomas, J. Organomet. Chem. 2001, 622, 61–65. 2001JOM109 C. Jones, A. F. Richards, J. Orgamomet. Chem. 2001, 629, 109–113. 2001MI275 G. Olive, A. Jacques, Molecules 2001, 6, 275. 2001MI1061 J. C. Dong, R. T. Li, T. M. Cheng, Chinese Chem. Lett. 2001, 12, 1061–1064. CAN 136:263192. 2001ZN(B)951 P. Christoph, F. Tabellion, A. Nachbauer, U. Fischbeck, F. Preuss, M. Regitz, Z. Naturforsch., Teil B. 2001, 56, 951–962. 2001ZOR207 M. A. Ishchenko, V. D. Nikolaev, A. A. Sokolov, S. V. Nikolaeva, Zh. Org. Khim. 2001, 37, 207–210. 2001ZOR1872 A. A. Pimenov, N. V. Makarova, I. K. Moiseev, M. N. Zemtsova, Zh. Org. Khim. 2001, 37, 1872–1873 (Chem. Abstr. 137, 20062). 2002CC1196 R. J. Baker, R. D. Farley, C. Jones, M. Kloth, D. M. Murphy, J. Chem. Soc., Chem. Commun. 2002, 1196–1197. 2002DOK210 E. M. Budynina, E. B. Averina, O. A. Ivanova, Y. K. Grishin, T. S. Kuznetsova, N. S. Zefirov, Dokl. Akad. Nauk 2002, 382, 210–213 (Chem. Abstr., 138, 4478). 2002HAC22 P. P. Onys’ko, A. A. Sinitsa, V. V. Pirozhenlo, A. N. Chernega, Heteroatom Chem. 2002, 13, 22–26. 2002JA14824 S. Suga, M. Watanabe, J. Yoshida, J. Am. Chem. Soc. 2002, 124, 14824–14825. 2002JCS(D)484 S. C. Clendenning, B. Gehrhus, P. B. Hitchcock, D. F. Moser, J. F. Nixon, R. West, J. Chem. Soc., Dalton Trans. 2002, 484–490. 2002JCS(D)1992 R. J. Baker, M. L. Cole, C. Jones, M. F. Mahon, J. Chem. Soc., Dalton Trans. 2002, 1992–1996. 2002JFC107 Y. V. Rassukana, K. O. Davydova, P. P. Onys’ko, A. D. Sinitsa, J. 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Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen)

203

Biographical sketch

Alaettin Gu¨ven is currently Associate Professor of organic chemistry at Chemistry Department at Anadolu University, Eskis¸ ehir, Turkey. He was born in Eskis¸ ehir-Turkey, received a B.Sc. in chemical engineering in 1976 and M.Sc. in Chemistry in 1987 from Anadolu University. He obtained a Ph.D. in 1992 under the direction of Dr. R. Alan Jones at UEA in Norwich, England. He held postdoctoral position from 2002 to 2003 in the laboratories of Professor Alan R. Katritzky at UFL in Gainesville, Florida. His scientific interests are computational chemistry, acidity, conformation, and tautomerism in heterocyclic systems.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 161–203

6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen, or Group 15 Elements; Also the Synthesis of Functions Containing Three Metals V. D. ROMANENKO and V. L. RUDZEVICH National Academy of Sciences of Ukraine, Kiev, Ukraine 6.06.1 INTRODUCTION 6.06.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENTS) 6.06.2.1 Synthesis of Functions Containing Three Metalloids 6.06.2.1.1 Functions bearing three silicons 6.06.2.1.2 Functions bearing three borons 6.06.2.1.3 Functions bearing three germaniums 6.06.2.1.4 Functions bearing mixed metalloids 6.06.2.2 Functions Containing Metalloids and Metals 6.06.2.2.1 Functions bearing silicon(s) and metal(s) 6.06.2.2.2 Functions bearing boron(s) and metal(s) 6.06.2.2.3 Functions bearing germanium(s) and metal(s) 6.06.2.2.4 Functions bearing mixed metalloid(s) and metal(s) 6.06.3 FUNCTIONS CONTAINING THREE METALS 6.06.3.1 Three Similar Metals 6.06.3.2 Three Dissimilar Metals

6.06.1

205 206 206 206 214 220 221 226 226 232 232 232 235 235 237

INTRODUCTION

This chapter outlines the synthesis and reactions of compounds of the general formula (XmE)n(LkM)3nCR (R = H or organyl; E = Si, Ge, or B; M = metal; X, L = any substituents; n = 0–3) having three heteroatoms (E, M) bonded to the same carbon. Much of the important pioneering work on these species was carried out in the 1970s and 1980s; COFGT (1995) covers the field up to 1994 <1995COFGT(6)171>. Use of the tris(trimethylsilyl)methyl (trisyl) group, (TMS)3C, in organometallic chemistry began with the demonstration that this function can be attached to a wide range of elements by simple ligand transfer from the lithium reagent (TMS)3CLi <1970JOM(24)529>. Since that time, numerous studies have shown that organometallic compounds containing the bulky ‘‘trisyl’’ group adopt a range of unprecedented structures and are 205

206

Functions Containing at Least One Metalloid (Si, Ge, or B)

much more chemically and thermally stable than analogous derivatives with smaller alkyl groups. This topic has been summarized in review articles <1996CCR125, 1995JOM(500)89>, both of which emphasize the progress made between 1985 and 1995, a period in which the use of trisilylmethanes in organic synthesis really began to grow. Within the period 1993–2003, functionalized trisilylmethanes and related compounds have emerged as uniquely useful ligand precursors <1999MI267>. It has been shown that the range of isolable organometallic compounds can be considerably extended by the use of ligands (XMe2Si)n(TMS)3nCH (n = 1–3) in which lone pairs from groups X can occupy sites in the metal coordination sphere. Moreover, the introduction of tripodal amino ligands of the type (RNHMe2Si)3CH into coordination chemistry has enabled the stabilization of new types of organometallic species with novel structural and reactivity patterns. In this chapter emphasis will be placed on the rapid and continuing developments, in the period 1993–2003, in the field of synthesis and reactions of the above compounds although most of that part of their chemistry which is concerned with the synthesis of C-hetero-substituted derivatives will be covered in Chapter 6.13. Whereas much information has been published about functions containing three metalloids, relatively little attention has been paid to functions bearing three metals. Nevertheless, despite the relative infancy of investigations directed to the use of these species in organic synthesis, attempts have been made to summarize and classify various compounds of the general formula (MLk)3CR. To eliminate complications introduced by the kind of E and M, the consideration is restricted here to compounds (EXm)n(MLk)3nCR, where C/E and C/M are bound via a -bond. Carboranes, metal clusters, and -metal complexes, of course, will not be treated.

6.06.2

FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENTS)

6.06.2.1 6.06.2.1.1

Synthesis of Functions Containing Three Metalloids Functions bearing three silicons

The various methods available for the formation of 1,1,1-trisilylalkanes can be divided into four categories. (i) ‘‘Direct synthesis’’ in the gas phase involving insertion of elemental silicon into a carbonhalogen bond of polychlorinated alkane such as chloroform (Equation (1)). Cl Cl

Cl

SiCl2X

Cu (cat.)

+ Si

XCl2Si

SiCl2X

H +

SiCl2Y + Others

Cl3Si SiCl2X

n

ð1Þ

X = H or Cl; Y = CH2SiCl2X; n = 1–3

(ii) Reductive silylation of trihalomethanes (the Merker–Scott procedure) (Equation (2)). SiR3

X X

X

+ nM + 3 SiX3R

R3Si

SiR3

ð2Þ

X = Cl, Br; R = alk; M = Li (n = 6), Mg (n = 3)

(iii) Reactions of organometallic carbon nucleophiles such as a Grignard reagent or an organolithium compound with halo- or alkoxy-silanes (Equations (3)). R13Si

–

SiR33 SiR23

+

R33SiX

–X–

R13Si

SiR23

ð3Þ

X = Cl, Br, OAlk; R = Alk, Ar

(iv) Derivatization and rearrangement of the compounds already containing polysilylated carbon or silicon units.

207

Functions Containing at Least One Metalloid (Si, Ge, or B)

When applicable, the Merker–Scott procedure is usually by far the most convenient and is therefore the method of choice. However, reactions of organometallic carbon nucleophiles with halosilanes probably represent the most general approach, which has provided various routes to trisilylmethanes not readily accessible by other methods.

(i) Trisilylmethanes and their linear C-organyl derivatives, (X3Si)3CR Direct reaction of elemental silicon with a mixture of CHCl3 and HCl has been studied in the presence of a copper catalyst at various temperatures in the range 280–340 C <1997OM93>. Tris(chlorosilyl)methanes with SiH bonds were obtained as the major products along with bis(chlorosilyl)methanes, derived from the reaction of silicon with CH2Cl2 formed by the decomposition of CHCl3 (Scheme 1). A related preparation of the compounds Cl3nMenSiCH(SiHCl2)2 and Cl3nMenSiCH(SiCl3)2 (n = 0–3) has been described starting from the dichloromethylsilanes Cl3nMenSiCHCl2 <1994USP5332849, 1995USP5399740, 2000MI1020>. Cu/Cd 300 °C

CHCl3 + HCl + Si

SiH2Cl

SiHCl2

SiHCl2

Cl2HSi

+

Cl2HSi

6%

SiHCl2 Cl3Si

SiHCl2

SiCl3 +

Cl2HSi

SiHCl2

+

16%

45%

SiCl3

SiCl3

+

Cl3Si

3%

SiCl3

+ High boilers + Bis(chlorosilyl)methanes 12%

trace

17%

Scheme 1

Tris(trichloromethylsilyl)methane 1 has been obtained by the one-step synthesis presented in Scheme 2. When CHCl3, SiHCl3, and Bun3N are allowed to react in the ratio 1:4.5:3, (Cl3Si)2CH2 is obtained in 90% yield; however, if a large excess (9 equiv.) of SiHCl3 is introduced in the reaction medium, the compound 1 is preferentially formed, isolated in ca. 30% yield as tris(ethoxysilyl) derivative 2 after ethanolysis. The latter could then be metallated on the central carbon atom and trapped with MeI. With CO2, insertion and rearrangement afforded the stable ketene, [(EtO)3Si]2C¼C¼O <1998JOM(562)79>. Cl Cl

+ 3SiHCl3 + 3Bun3N

Cl

SiCl3

i Cl3Si

SiCl3

ii 30%

1 Si(OEt)3 (EtO)3Si

Si(OEt)3

Si(OEt)3

iii

–

(EtO)3Si

Si(OEt)3

iv 95%

[(EtO)3Si]3CMe

2 i. MeCN, –40 °C; ii. EtOH, –40 °C; iii. ButLi, THF, –80 °C; iv. MeI, THF, –80 °C

Scheme 2

Interest in 1,1,1-tris(organylsilyl)alkanes has also continued. Tris(trimethylsilyl)methane, (TMS)3CH, and related compounds have been intensively studied in the late 1990s and early 2000s in respect of their molecular geometry, ionization potentials, conformational structure, and molecular dynamics <1999CEJ3501, 1999MI219, 1997OM5218, 2000JCS(D)4312, 1994JCS(P2)2555>. Determination of the solution acidity of (TMS)3CH supports earlier findings <1994JA8304> that this compound is a significantly weaker acid (pK 36.8) than the corresponding silicon analog (TMS)3SiH (pK 29.4) <2002OM3157>. Consequently, (TMS)3CLi is a significantly stronger base than (TMS)3SiLi. This suggests that silicon accommodates a negative charge

208

Functions Containing at Least One Metalloid (Si, Ge, or B)

much more effectively than carbon, despite its lower electronegativity (C 2.5, Si 1.7). Reich and co-workers have prepared 13C-labeled tris(TMS)methane from commercially available 13C-paraformaldehyde (Scheme 3). This synthesis involves several in situ electrophilic traps, which take advantage of the differing reactivities of the starting materials, products, and electrophiles toward metallating agents <1998MRC118>.

(C13H2O)n + PhSeH

i 100% crude yield

PhSe

ii 81%

C13H2 PhSe

TMS C13 TMS SePh

iv 90%

TMS C13 PhSe SePh

iii 97%

TMS C13 TMS TMS

i. BF3·OEt2,CHCl3, 0 °C, 4 days; ii. TMS–Cl, LDA, THF, –78 °C, 2 h; iii. BunLi, THF, –78 to –20 °C, TMS–Cl

Scheme 3

A modification of the Merker–Scott procedure, involving the reaction between CHBr3, R3SiCl, and BunLi has been extended to numerous sterically crowded tris(organyl)chlorosilanes; an example is the preparation of the tris(i-propyldimethylsilyl)methane (Equation (4)). The latter can be used to attach the bulky trisilylmethyl group to a metalloid or metal center, was demonstrated by treating the lithium reagent, (PriMe2Si)3CLi, with Me2HSiCl to give a 77% yield of (PriMe2Si)3CSiMe2H <1995JOM(489)181>. Other examples relate to trisilylmethanes (RMe2Si)3CH (R = o-Tol, Et) <1996JOM(510)117, 1998JOM(555)263>. Metallation of (o-TolMe2Si)3CH by MeLi in tetrahydrofuran (THF) was shown to be much slower than that of (PhMe2Si)3CH. The lithium salt reacts with MeI to give (o-TolMe2Si)3CMe, but neither with Me2SiHCl nor with a range of other organosilicon halides <1996JOM(510)117>. A further extension of this type of chemistry was the development of arene-catalyzed lithiation of polychlorinated compounds under the Merker–Scott conditions. The reaction of 1,1,1-trichloroalkanes with a large excess of lithium metal (1:20 molar ratio) in THF in the presence of chlorotrimethylsilane and a catalytic amount of 4,40 -di-t-butylbiphenyl (DTBB) was found to produce 1,1,1-trisilylalkanes in good yield (Equation (5)). Conditions for preparing the monoand disilylated compounds have also been described <1996T1797>. Br Br

Br

+

Cl3CR

3PriMe

2SiCl

+

3BunLi

SiMe2Pri

–78 °C, THF 60%

TMS–Cl, Li (1:20), DTBB (5 mol.%) 51–93%

PriMe2Si

SiMe2Pri

ð4Þ

(TMS)3CR

ð5Þ

R = H, D, Me, Ph DTBB = 4,4'-di-t-butylbiphenyl

The obvious thought of using combination of the Merker–Scott procedure and the reaction of an organolithium compound with the corresponding halosilane for the synthesis of trisilylmethanes with different silyl groups attached to the carbon atom was realized for the compounds 4 and 5 <1997OM4728>. Treatment of CHBr3 at low temperature with 3 equiv. of BunLi in the presence of 3 equiv. of Me2PhSiCl gave trisilylmethane (PhMe2Si)3CH. When 2 equiv. of Me2PhSiCl/BunLi was used, the product was bromodisilylmethane 3, and this was converted into trisilylmethane 4 by treatment with BunLi/TMS-Cl. In the same way, the compound 5 was obtained by use of 2 equiv. of TMS-Cl/BunLi in the first step and 1 equiv. of BunLi/Me2PhSiCl in the second step (Scheme 4). Good yields could be obtained at each stage, provided the temperature was rigorously controlled. The attachment of the very bulky (PhMe2Si)3C ligand or of the closely related (TMS) (Me2PhSi)2C and (TMS)2(Me2PhSi)C ligands to a metal center made possible the isolation of a number of metal derivatives (TMS)3n(Me2PhSi)nCM: n = 1, M = Li(tetramethylethylenediamine [1,2-bis(dimethylamino)ethane] (TMEDA)), Li(Et2O), Na(TMEDA); n = 2, M = Li(THF)2, Li(TMEDA), K; n = 3,

209

Functions Containing at Least One Metalloid (Si, Ge, or B)

M = Rb or Cs <1997OM4728>. For further details of this subject, readers are referred to the following articles and references therein <1998JOM(564)215, 1997OM5653, 1996JOM(510)143>. Eaborn and co-workers have subsequently introduced the closely related dicarbanionic ligand [C(TMS)2SiMe2CH2CH2Me2Si(TMS)2C] (R-R) <1999OM2342>. Its precursor HR-RH 6 was prepared by the reaction shown in Scheme 5 <1996OM1651>. The compound 6 was metallated with MeLi in THF in the presence of TMEDA to give the chelated salt 7. If no TMEDA is added, a solid compound, assumed to be [(R-R)Li], may be isolated in 80% yield from diethyl ether/hexane. The lithium salt can be used to make cyclic derivatives of mercury <1996OM1651>, lead <1997OM5621>, potassium, zinc, ytterbium, tin <1999OM2342>, manganese, and cesium <2000OM1190>. The structurally related disiloxane [(TMS)2CHMe2Si]2O has also been prepared, and shown to undergo metallation reaction leading to a novel molecular species incorporating a cyclic organolithate anion and disiloxane-solvated lithium cation <1998CC1277>. Br Br

Br

i Br

Li

ii SiMe2Ph

PhMe2Si

PhMe2Si

TMS

iii SiMe2Ph

Br

iv TMS

SiMe2Ph

PhMe2Si

3

4

Li

ii TMS

TMS

SiMe2Ph

v TMS

TMS

TMS 5

i. 2PhMe2SiCl/2BunLi, THF, –80 °C; ii. BunLi, Et2O, –78 °C; iii. TMS–Cl, Et2O, –78 °C; iv. 2TMS–Cl/2BunLi, THF, –80 °C; v. PhMe2SiCl, Et2O, –78 °C

Scheme 4

TMS Li + ClMe2Si

2

SiMe2Cl

THF, reflux, 4 h 82%

TMS

SiMe2 Me2Si TMS TMS TMS TMS 6

MeLi/ TMEDA THF, 6 h, 20 °C 69%

Me2Si TMS TMS

SiMe2 [Li(TMEDA)2]+ TMS Li TMS 7

Scheme 5

The reaction of (TMS)2CHLi with hexachlorodisilane has been explored as a means of synthesizing tetrachlorodisilane 8 <2001IC3766>. Starting from 8 a wide variety of 1,2-bis[bis(TMS)methyl]substituted disilanes were prepared (Scheme 6). A reduction of 8 with LiAlH4 resulted in the formation of the disilane 9 and the metathesis with Me3SnF yielded the tetrafluorodisilane 10. The interaction of 8 with a solution of sodium in liquid ammonia at 78 C affords the tetraaminodisilane 11. In turn, treatment of 11 with reagents containing acidic protons (HBr, HI, or H2O) leads under elimination of NH3 to the tetrabromo- 12, tetraiodo- 13, and tetrahydroxydisilane 14. The siliconsilicon bonds were not cleaved under these conditions. The disilane 14 can also be obtained directly from the reaction of tetrachlorodisilane 8 with a mixture of H2O2/H2O. However, in contrast to 8, the tetraaminodisilane 11 reacted under the same conditions to yield the trihydroxycyclotrisiloxane 15 <2002OM3671>. The synthetic utility of 11 has also been demonstrated by the reaction with liquid H2S at 70 C leading to the formation of a S4Si4 cage compound 16 <2001OM1282>. The driving force for the crossover arrangement of the sulfur atoms is most likely the formation of the four five-membered rings. Finally, a somewhat similar chemistry was performed with (TMS)2CHSiCl3. The ammonolysis of this compound with ammonia which was not predried with sodium yielded the trihydroxycyclotrisilazane 17 while the reaction with sodium in predried ammonia gave the acyclic tetraaminodisilazane 18 <2000EJI827>.

210

Functions Containing at Least One Metalloid (Si, Ge, or B) TMS Li

+ Si2Cl6

TMS

i 53%

Cl Cl Si Si Cl Cl

TMS TMS

TMS TMS

ii 85%

TMS TMS

TMS TMS

H H Si Si H H

76%

TMS

TMS

TMS

TMS

TMS TMS

10

8 ii

F F Si Si F F

iv 82% NH2 NH2 TMS Si Si NH2 NH2 TMS

9

v–vii 74–86%

11

TMS TMS

X X Si Si X X

TMS TMS

12, X = Br 13, X = I 14, X = OH

i. toluene, reflux, 6 h; ii. LiAlH4, THF, –78 °C; iii. Me3SnF, toluene, reflux, 15 min; iv. Na /NH3, –78 °C; v. HBr, toluene, 20 °C, 30 min; vi. HI, toluene, 20 °C, 30 min; vii. H2O, THF, reflux, 20 h

Scheme 6

OH R Si O R O Si HO Si O OH R 15

R R

S Si S

Si

R

Si S Si R S 16

OH Si NH R HN Si Si NH OH HO R 17 R

H N H2N NH2 Si Si R R NH2 NH2 18

R = (TMS)2CH

(ii) Functionalized trisilylmethanes containing an ‘‘active’’ ligand framework The extreme exploitation of the steric demand of an Si3C function is a common feature of most of the early reports on trisilylmethane chemistry <1996CCR125, 1995JOM(500)89>. The emphasis in studies on trisilylmethane derivatives has moved toward polydentate compounds of the type (XMe2Si)3n(TMS)nCH, n = 0–2, in which the trisilylmethyl ligands have bulk similar to that of the (TMS)3C, but contain groups X bearing heteroatoms with lone pairs capable of coordinating intra- or intermolecularly to the metal. The most prominent example of the versatility of this concept is the structural chemistry and chemical reactivity of a series of compounds studied by Eaborn and co-workers. Those include functionalized trisilylmethanes (Me2NMe2Si)(TMS)2CH <1999OM45>, (Me2NMe2Si)3CH <1996CC741, 1997OM503, 1998OM3135>, (MeOMe2Si) (TMS)2CH <1996JOM(521)113, 1996OM4783, 1997AG(E)2815, 1997OM5653, 1998OM4322>, (MeOMe2Si)3CH <1992JCS(D)1015>. Typically the compounds (XMe2Si)3n(TMS)nCH are obtained in several steps via the corresponding bromosilanes. Representative examples are given in Scheme 7 <1999JCS(D)3267>. Interestingly, the reaction between compound 19 and BunLi proceeded much faster than the corresponding reaction with (TMS)3CH suggesting that it is facilitated by initial coordination of Me2N to lithium. The compound 20 reacted with MeLi at 0 C to give a complex mixture that, after aqueous work-up, was found to contain (MeOMe2Si) (TMS)2CH, indicating that MeLi had attacked SiOMe as well as CH bonds. However, the reaction between 20 and Pri2NLi proceeded smoothly at 60 C and the lithium compound (MeOMe2Si)2(TMS)CLi was isolated in good yield. The symmetrically substituted tris(aminosilyl)methanes (RNHMe2Si)3CH are available from the reaction of (BrMe2Si)3CH 21 with 3 equiv. of a primary amine in the presence of an excess of triethylamine as auxiliary base. The facile accessibility of these compounds along with the possibility of preparing enantiomerically pure derivatives provided the motivation for the synthesis of an extensive series of novel trisilylmethane-derived tripodal amines and the corresponding trilithium triamides (Scheme 8). A comprehensive study into the coordination chemistry of

211

Functions Containing at Least One Metalloid (Si, Ge, or B)

these ligands has been carried out by Glade and co-workers <2002JCS(D)2608, 2001CEJ2563, 2001EJI1425>. Interestingly, the tris(aminosilyl)methanes were found to be in equilibrium in solution with the cyclic diamines, which are generated upon ejection of one molecule of the primary amine. Reaction of these equilibrium mixtures with 3 equiv. of BunLi affords the trilithium triamides. It is notable that the result of the metallation is the same whether the reaction is carried out with the essentially pure tripodal amine or with a mixture of the triamine and the cyclic product in the presence of the dissociated primary amine (Scheme 9) <2001CEJ2563, 2001MI191,1994IC3064>. TMS

TMS

i

SiMe2Ph

PhMe2Si

BrMe2Si

TMS

ii or iii

SiMe2Br

XMe2Si

4

SiMe2X

19, X = Me2N 20, X = MeO

i. Br2/Al, petroleum, 2 h, 0 °C; ii. Me2NH, petroleum, –60 °C, 84%; iii. MeOH/Et3N, petroleum, 20 °C, 83%

Scheme 7

H

Mg

HCBr3 + 3Me2Si(H)Cl

THF

H

3Br2

Me2Si SiMe2 SiMe2 H H H H

3RNH2, 3Et3N

Me2Si SiMe2 SiMe2 Br Br Br

Me2Si SiMe2 SiMe2 NH NH NH R R R

21 R = But <1993IC2308>, Ph <1994IC3064>, 2-FC6H4 <1995IC4062>, 4-FC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4 <1994IC3064>, 2-MeOC6H4 <2002EJI1968>, 4-methyl-2-pyridyl, 4,6-dimethyl-2-pyridyl <1997OM5585>, (S)-Ph(Me)CH <1994IC3064, 1996OM3637, 2001CEJ2563>, (R)-4-MeOC6H4(Me)CH <2001MI191>, (R)-1-tetralenyl <2001JCS(D)964>, (S)-But(Me)CH <2001EJI1425>, (S)-1-(1-naphthyl)ethyl <2002PO629>, (R)-1-indanyl <2001CEJ2563>

Scheme 8

H Me2Si

H Me2Si SiMe2 SiMe2 NH NH NH R R R

R

SiMe2

N +

SiMe2 NH R

RNH2

H BunLi

Me2Si

SiMe2 SiMe2 Li N N N R Li Li R R

R = (S)-Ph(Me)CH, (R)-1-indaryl, (R)-4-MeOC6H4(Me)CH

Scheme 9

Tris(diphenylphosphinodimethylsilyl)methane 22 has been prepared from the reaction of 21 and Ph2PLi (yield 62%) <1999CJC1931> or Ph2PK (89%) <1999JCS(D)831>. The compound 22 reacted with [Mo(CO)6] to give the complex cis-23, in which two phosphine groups are coordinated to molybdenum and one is free and with BunLi in the presence of TMEDA to give [Li(TMEDA)2][(Ph2PMe2Si)3C] which contains discrete planar carbanions and no LiP coordination

212

Functions Containing at Least One Metalloid (Si, Ge, or B)

<1999JCS(D)831>. The susceptibility of 22 to cleavage of the PSi bonds by protic reagents has also been described <1999CJC1931>. Hydrolysis of the PSi bond in 22 produces principally the alcohol 24. In the presence of excess of methanol, the compound 22 is cleanly converted to the trisilylmethane 25. Bubbling oxygen through solutions of 22 for 15 min gives only trace amounts of the oxidation product 26 (Scheme 10).

H Me2Si Ph2P

SiMe2 PPh2

H SiMe2

Mo(CO)6

PPh2

Toluene, reflux 90%

Me2Si Ph2P

SiMe2 PPh2

SiMe2 PPh2

(OC)4Mo

22

23 H HX or O2 Toluene, 20 °C

Me2Si X

SiMe2

SiMe2 X

X

24, X = OH 25, X = OMe 26, X = OP(O)Ph2

Scheme 10

Other examples of this type of functionalized trisilylmethanes are (Ph2PCH2Me2Si)3CH, (Ph2PCH2Me2Si)2(TMS)CH, and (Ph2PCH2Me2Si)(TMS)2CH <2000JCS(D)2183>. The conversion of triphosphino derivative to the corresponding lithium salt was affected by MeLi in ether. The anionic ligand in compound (Ph2PCH2Me2Si)3CLi shows a close skeletal resemblance to the tripodal ligands in silatranes, but the coordination to the metal center is provided by the lone pair of electrons of the carbanion rather than by that of the nitrogen atom. The [dimethyl(2-pyridyl)silyl]-bis(TMS)methane, (2-PyMe2Si)(TMS)2CH, containing a nitrogen atom in its ligand periphery was synthesized by reaction of (BrCH2Me2Si)(TMS)2CH with 2-lithiopyridine (yield 61%). This ligand precursor reacts with MeLi in THF to give the lithium derivative, which could be used to obtain compounds of a wide range of metals (K, Mg, Cr, Mn, Co, Ni) <2000OM3224, 2000CC691>. Synthesis of more sophisticated trisilylmethane-based polydentate species is shown in Scheme 11. Preparation of the compound 27 was readily achieved by reaction of 3 equiv. of propynyl lithium with 1 equiv. of 21. Reaction of this precursor with an excess of the 4,6-di-t-butyl-1,3,2-diazaphosphinine yields intermediate 28. In a subsequent step, 28 was reacted with trimethylsilylacetylene to give the desired ligand 29. Complex of 29 with [Mo(CO)5(THF)] has also been characterized <2000EJI2565>.

(iii) Compounds with an Si3C function as part of one or more ring systems Tris(aminosilyl)methanes, HC(SiMe2NHR)3, have been shown to be valuable starting materials to build up compounds in which the trisilylmethane unit is part of a hetero-bicyclo[2.2.2]octane system. After lithiation with n-butyllithium, these amines react with early transition metals (Y <1995IC4062>, Ti <1997OM5585, 2001CEJ2563>, Zr <1995IC4062, 1999JOM(591)71, 2000OM963, 2001EJI1425>, Hf <1999JOM(591)71>, Nb <1997OM5585>) as well as groups 13 (Tl <2001CC899>, Sn and Pb <1995IC4069, 1995CB29, 1998POL737, 2001ZAAC(627)1417>) and 15 (Sb, Bi <2000IC3931>) metals to form complexes with tripodal amido ligands. Some examples taken from the studies by Gade and co-workers are shown in Scheme 12. Related hetero-bicyclo[2.2.2]octanes containing chalcogens instead of the nitrogen atoms are formed in a smooth reaction from easily available HC(SiMe2Cl)3, RMCl3 (M = Si, Ge, or Sn), and a suspension of Li2E (E = S or Se) in THF (Scheme 13) <2002JOM(660)27>. A new synthetic approach toward hexasilabicyclo[2.2.2]octane system, in which three SiSi linkages are aligned in parallel between two bridgehead carbons, is conceptually based on triple silylation of two molecules of a trilithiomethane equivalent with three molecules of dichlorodisilanes

213

Functions Containing at Least One Metalloid (Si, Ge, or B) H i. 3Me2SiHCl, Mg, THF

HCBr3

Me2Si

ii. Br2, benzene

Br

THF, –78 °C

Br

Br

Li

3Me

SiMe2

SiMe2

21

Me2Si

SiMe2

But

But

H

3

SiMe2

N

H

N

P

Me2Si

Me

Toluene, 100 °C, 3 h Me

Me

P

SiMe2

P P N N

N

–3ButCN

Me

SiMe2

But

Me

But

But

27

28 H Me

Me2Si

3TMS Toluene, ∆

SiMe2

P

–3ButCN

SiMe2

Me

P

P

TMS TMS

TMS 29

Scheme 11

H Me2Si

SiMe2 SiMe2 Li N N N R Li Li R R

ZrCl4

TlCl3

Me2Si N R

SiMe2 N

R

H

H

H SiMe2

Me2Si N

N R

R

Tl

R Cl

SiMe2 N

MCl3

MCl2

SiMe2

Me2Si

SiMe2

N

N R

R

Zr

R

Cl Li (OEt ) 2 2

H SiMe2

Me2Si

N

N M

N R

–

Li(THF)n+

M = Sn, Pb

R

R

SiMe2

SiMe2 N

N

R

M

M = Sb, Bi

Scheme 12

TMS TMS

TMS

SiMe2Cl

3MeCOCl/AlCl3 Hexane, 0 °C 82%

ClMe2Si

SiMe2Cl

H R-MCl3/3Li2E Hexane, rt 45–70%

M = Si, Ge, Sn; E = S, Se; R = Me, Ph, H2C=CH–

Scheme 13

Me2Si

SiMe2

E E M R

SiMe2 E

214

Functions Containing at Least One Metalloid (Si, Ge, or B)

as illustrated in Scheme 14. Commercially available bis(phenylthio)methane was selected for a trilithiomethane equivalent because the phenylthio group facilitates deprotonation and stabilizes the anionic center. Moreover, the group is readily removed by metallation to give rise to the lithium derivative. Reduction of the disilane 30 with lithium radical anion and its silylation with (ClSiMe2)2 lead to 1,2,4,5-tetrasilacyclohexane 31 as a stereoisomeric mixture (cis:trans = 1:1). Final ring formation for hexasilabicyclo[2.2.2]octane 32 was attained by reduction of 31 and subsequent silylation with (ClSiMe2)2 <1998CL1145>.

PhS 2 PhS

PhS

BuLi

2

THF, 0 °C

Li PhS

PhS

SPh

(ClSiMe2)2

PhS

–78 °C to rt 94%

PhS

Li

Si Si PhS

82%

Li

SPh

LDBB THF, –78 °C

30

(ClSiMe2)2

Si Si

SPh Si Si

SPh

LDBB

Si Si 31 (1/1 cis/trans)

Si Si Li

Li

Si Si H Si Si Si Si H

(ClSiMe2)2

Si Si

73%

32 Li+

LDBB =

Scheme 14

Functionalization of 32 at bridgehead carbon was achieved by treatment with BunLi-ButOK followed by a reaction with electrophile (Scheme 15). It is noteworthy that only monosilylation occurs. Probably through-space or through-bond electrostatic interaction prevented the formation of a bridgehead dianion. Nevertheless, a stepwise procedure involving deprotonation of 32 followed by electrophilic quenching allowed preparation of symmetrically or dissymmetrically disubstituted derivatives <2000JOM(611)12, 2001CL1090>. Further extension of this synthetic strategy is illustrated in Scheme 16. Synthesis of cage compounds 36 and 37 containing a trisilane linkage was achieved starting from the acyclic trisilane 33. Reduction of 1,3,4,5-tetrasilacyclohexane 34 with lithium radical anion effectively produced 1,3-dimetallic reagent 35 which, upon quenching with Me2SiCl2, gave pentasilabicyclo[3.1.1]heptane 36. Silylation of 35 with Cl(SiMe2)2Cl also proceeded successfully, giving rise to 2,3,4,6,7,8-hexasilabicyclo[3.2.1]octane 37 <2000JOM(611)12>. The reaction of tris[dimethyl(ethynyl)silyl]methane with triethylborane was reported to proceed via a threefold 1,1-ethylboration to give a bicyclic compound incorporating trisilylmethane unit <1995CC399>.

6.06.2.1.2

Functions bearing three borons

The first synthesis of triborylmethane derivatives was reported in 1968, by Matteson and Castle who obtained tris(dimethoxyboryl)methane, CH[B(OMe)2]3, by treatment of (MeO)2BCl and CCl4 with

215

Functions Containing at Least One Metalloid (Si, Ge, or B) Si Si H Si Si Si Si H

Si Si H Si Si

BunLi-ButOK THF, –42 °C

Si

Si Si H Si Si Si Si R

RX

Si M

32

i. BunLi-ButOK ii. MeI

Si Si Me Si Si Si Si

Si Si H Si Si Si Si

TMS

TMS

RX, R, yield: MeI, Me, 97%; CH2=CHCH2Br, CH2=CH–CH2, 94%; PhCH2Br, PhCH2, 85%; Me2PhSiCl, Me2PhSi, 90%; Me2[Cl(CH2)3]SiCl, SiMe2[(CH2)2Cl], 86%; Bu3SnCl, Bu3Sn, 88%; (PhS)2, PhS, 62%; I2, I, 77%

Scheme 15

Si

Si

i. BuLi-ButOK ii. Me2SiCl2

Si

PhS

SPh

THF, –78 °C

33

Si PhS

Si

Si

Si

Si

LDBB SPh

THF, –78 °C

34

Si

Si Li

35

Me2SiCl2 63%, –40 °C

Cl(SiMe2)2Cl

Si

–40 °C, 62%

Si H

Si Si Si H

Li

Si

H Si Si Si H

Si

36

Si Si

37 Li+

LDBB =

Scheme 16

lithium in THF <1968JA2194>. Subsequently, tris(dichloroboryl)methane, CH(BCl2)3, was synthesized by an exchange reaction of tris(dimethoxyboryl)methane with boron trichloride <1973IC2472, 1995COFGT(6)171>. Siebert and co-workers have reported the synthesis of 1,1,1-tris(dichloroboryl)alkanes and tris(boronate)esters via hydroboration of alkynylboronates using in situ generated HBCl2 <2001EJI373, 2002EJI1293>. In addition, Marder and co-workers have described a catalytic route to the tris(boronate)esters in a single step from readily accessible vinylboronates <2002JOM(652)77>. New acyclic systems bearing three dialkylboryl groups on a single carbon atom have also been prepared <1998AG(E)1245>.

216

Functions Containing at Least One Metalloid (Si, Ge, or B)

(i) 1,1,1-Tris(dihaloboryl)alkanes 1,1,1-Tris(dichloroboryl)-3,3-dimethylbutane 38 is now readily available on a large scale by lithiation of 3,3-dimethyl-1-butyne by n-butyllithium, followed by boron/lithium exchange with BCl3 and a double hydroboration of the boryl alkyne with dichloroborane (HBCl2) prepared in situ (Scheme 17). This reaction sequence afforded a 42% yield of 38 <2002EJI1293>. Treatment of trimethylsilylacetylene with BunLi, BCl3, and 2 equiv. of HBCl2 provided 1,1-bis(dichloroboryl)2-trimethylsilylethene 40 and isomeric products 41–43 (Scheme 18) <2002EJI1293>. Presumably, the hydroboration of 39 occurs regioselectively to give bis(dichloroboryl) derivative 40. Dichloroborane then hydroborates 40 in both directions, giving rise to the compounds 41 and 42, with the former being favored. The mechanism of the formation of 43 is unclear.

BCl2

i, ii

BCl2 BCl2 BCl2

iii 42%

38

i. BunLi, pentane, –15 °C; ii. BCl3, pentane, –78 °C; iii. BCl3/Me3SiH (2 equiv.), pentane, –30 °C

Scheme 17

i. BuLi ii. BCl3

TMS

TMS

–LiCl

BCl2

2HBCl2

BCl2

+

39

BCl2 BCl2 BCl2

TMS

BCl2

TMS 40

Cl2B

BCl2 +

+ TMS

BCl2

Cl2B Cl2B TMS

42

41

BCl2

43

Scheme 18

(ii) Methanetriboronic esters The preparation of tris(ethylenedioxyboryl)methane 45, a reagent for the homologation of aldehydes and ketones under nonacidic conditions, was improved by avoiding the isolation of the intermediate tris(dimethoxyboryl)methane. The compound 45 is best prepared from the dimethoxyboron chloride, chloroform, and lithium dispersion by transesterification of crude methyl ester 44 with ethylene glycol and subsequent crystallization of the product from hot THF (Scheme 19) <1995T11219>.

MeO

Cl Cl

Cl

+ 3ClB(OMe)2

+

MeO

6Li –30 to 20 °C

B

OMe B B OMe OMe 44

Scheme 19

O

OMe HO

OH

THF, 0 to 70 °C 16%

O

B

B O

O B O

45

O

217

Functions Containing at Least One Metalloid (Si, Ge, or B)

Knowledge of the versatile reactions of boranes with unsaturated compounds prompted an investigation into the synthesis of methanetriboronic esters via alkynes. Siebert and co-workers have shown that the interaction of the catechol-substituted monoborylacetylene 46 with an excess of 1,3,2-benzodioxaborole (catecholborane) leads to a mixture of 1,1-bis(1,3,2-benzodioxaborol-2-yl)ethene 47 and a small amount of trans-1,2-bis(1,3,2-benzodioxaborol-2-yl)ethene 48. In contrast with catecholborane, dichloroborane adds to 47 affording triborylethane 49, which was identified as a catechol ester 50. The direct hydroboration of 46 with 2 equiv. of HBCl2 and subsequent reaction with catechol also affords 50 in 83% yield (Scheme 20) <2001EJI373>.

Bcat

O

O +

B

HB O

O

+

80 °C

Bcat

46

48

47

2HBCl2

HBCl2

OH

OH Me

Bcat catB

Bcat BCl2 BCl2

2 OH –4HCl

Me

Bcat Bcat Bcat

OH –2HCl

Me

Bcat BCl2 Bcat

78% 50

49

O Bcat = –B O

Scheme 20

The transition metal-promoted catalytic diboronation of diborylacetylenes offers another new route to compounds containing a B3C function <1999EJI1693>. Thus in refluxing toluene, the platinum complexes [Pt(PPh3)2(C2H4)] or [Pt(PPh3)4] catalyze the double diboronation of the diborylacetylene 51 with the catechol-substituted diborane 52 to give the hexaborylethane 53 (Scheme 21). Reaction conditions were found to be critical; the formation of tetraborylethane 54 instead of hexaborylethane occurs by catalysis with [Pt(PPh3)2(C2H4)] or [Pt(PPh3)4] in THF at 55 C. Moreover, the tetraborylethene 55 is obtained from 51 and 52 with the base-free platinum complex [Pt(COD)2] under mild conditions in toluene. At temperatures above 40 C 55 adds 52 to form hexaborylethane 53. Hexaborylethane derivatives have also been obtained from the diborylacetylene 56 and the diborane 52. However, the reaction leads to a mixture of naphthalene- and benzo-1,3-dioxa-2-borol-2-ylethanes, in which between five and two boryl substituents of 52 and between one and four substituents of 56 are incorporated. It is unclear whether the exchange occurs before or after the formation of the hexaborylethanes. The route employing transition metal-catalyzed diboration of borylalkenes appeared to be a general method for synthesizing tris(boronate)esters, as further examples demonstrate. Diboration of the styrylboronate esters 57 with diborane 52 in the presence of a variety of rhodium phosphine catalysts gives predominantly either 58, which contains three boronate ester groups on the carbon atom, or its isomer 59. Wilkinson’s catalyst, [Ph(PPh3)3Cl], gave the highest yield of 58, 75% and 71% for 58a and 58b, respectively, with the reactions essentially going to completion (Equation (6)). The formation of 58 apparently involves regiospecific insertion of the vinylboronates into a RhB bond followed by -hydride

218

Functions Containing at Least One Metalloid (Si, Ge, or B)

elimination, another regiospecific insertion of the 2,2-vinyl bis(boronate) into the remaining RhB bond followed by CH reductive elimination leading to 2,2-diboration and a 2,1-hydrogen shift <2002JOM(652)77>. O

O B

B

O

O 51

catB catB catB

(Ph3P)2Pt(C2H4)

+ O

Toluene, reflux, 24 h

O

71%

B B O

Bcat Bcat Bcat

O 53

52

52 >40 °C (Ph3P)2Pt(C2H4)

Pt(COD)2

catB

Bcat

55 °C, 24 h

Toluene, 40 °C, 48 h 70%

catB

Bcat 55

Bcat

H catB catB

O

O

Bcat

B

B

O

H

O 56

54 O Bcat = –B O

Scheme 21

O

Bcat

O +

B B O

O 52

Rh(PPh3)3Cl (1 mol.%) THF, 58 °C, 12 h

Ar

Ar

Bcat Bcat Bcat 58

57

catB

Bcat

Ar

Bcat

+

59

ð6Þ

O Ar = Ph (a), 4-MeOC6H4 (b); Bcat = –B O

(iii) Tris(boryl)alkanes and boracycloalkanes involving a B3C function 1,1,1-Tris(diethylboryl)alkanes have been postulated and evidenced in many reactions of borylacetylenes with diethylborane <1994AG(E)2296, 1995CC1691, 1998AG(E)1245>. For example, hydroboration of trimethyl(propyn-1-yl)silane with Et2BH under ‘‘hydride bath’’ conditions (i.e., with a large excess of diethylborane) leads to the 1-carba-arachno-pentaborane(10) derivative 64. The reaction proceeds via intermediate formation of compounds 60–63. In the hydride bath, exchange reactions between in situ generated 1,1,1-tris(diethylboryl)propane 62 and geminal bis(diethylboryl)alkane 63, take place until the carborane skeleton 64 is formed (Scheme 22) <1997CCC1254>. A thermally stable tris(boryl)ethane has been derived from the interaction of 50 with t-butyllithium. This reaction results in the formation of 1,1,1-tris[di(t-butyl)boryl]ethane 65, which does not form any closo-C2B3 carborane by elimination of trisorganoboranes (Equation (7)) <2001EJI373>.

219

Functions Containing at Least One Metalloid (Si, Ge, or B) TMS

Me

TMS

Et2BH

+

Me +

Et2B

Me

Et2B 60

61 Et2BH

Et2B Et2B Et2B

Et

+

Et2B

TMS

Et2B

Et 63

62 3Et2BH

–4BEt 3

Et Et B Et Me2HSi

B BH B

Et H

Et

H Et

64

Scheme 22 catB catB

6ButLi Me

catB

–3C6H4O2Li2

50

Bu2t B Bu2t B

Me

Bu2t B

ð7Þ

65 O

Bcat = –B O

Siebert and co-workers also found that cyclic tetraborylmethane 67 is formed in excellent yield upon addition of B2Cl4 to a solution of boriranylideneborane 66 in hexane at low temperature. The substitution of the chlorine atoms of 67 by amino groups yields the triamino derivatives 68 with unexpected cleavage of one of the exocyclic CB bonds (Scheme 23) <2001EJI387>. HNEt2 or Bu TMS

t

B

B

But

TMS

B2Cl4 Hexane, –85 °C

TMS

92%

But B Cl

TMS–NMe2 or 2LiN(CH2)4

TMS

B Cl

B Cl But

Hexane, –30 °C 32–48%

TMS

67

66 R2N = Me2N, Et2N,

TMS

Cl B

NR2 But B B NR

2

B H NR2 68

N

Scheme 23

A route to boracycloalkanes possessing closo-C2B3 carborane structure, which may be described as midway between classical and nonclassical, uses thermolysis of the triborylalkane 38. On heating neat 38 at 170 C, elimination of BCl3 occurred with formation of the compound 69.

220

Functions Containing at Least One Metalloid (Si, Ge, or B)

Methylation of 38 with Al2Me6 gave 70, which, on heating, was transformed into 71. The latter was also formed by direct methylation of 69 with MeLi or Al2Me6. Treatment of 69 with 3,3-dimethylbutynellithium and 2-phenylethynyllithium afforded 72a and 72b, respectively (Scheme 24). Attempts to substitute the chloro atoms with OH, OMe, OBut, and catechol groups were unsuccessful. With sterically demanding lithium, reagents such as ButLi, Pri2NLi, BunLi, and PhLi only product mixtures were obtained <2002EJI1293>. But

But R

BCl2 BCl2 BCl2

But

–BCl3 170 °C, 2 h; 25%

Cl

Cl B B

R

B

Cl

Li

Hexane, –78 °C 62–67%

B

R But

69

Al2Me6

hexane, –78 °C 83%

B

R

But

38

B

72a,b

MeLi or

Et2O, –70 °C

Al2Me6

75%

R = But (a), Ph (b)

But BMe2 BMe2 BMe2

But

Me –BMe3 Me toluene, reflux, 2 h

B

B

B

Me

But

70

71

Scheme 24

6.06.2.1.3

Functions bearing three germaniums

Traditionally, trigermylmethane derivatives are synthesized either via condensation of the polylithiated hydrocarbons with chlorotrimethylgermane or via stepwise base-assisted introduction of an R3Ge group into compounds containing an activated methyl group <1995COFGT(6)171>. Kouvetakis and co-workers have utilized the high reactivity of dihalogermylenes toward CHal bonds to develop probably the most general and effective synthesis of simple trigermylmethanes <1995IC5103, 1996CM2491, 1998JA6738>. They found that the germylene complexes GeX2.dioxane (X = Cl, Br) undergo complete insertion into the CBr bonds of CBr4 to give the tetrakis(trihalogermyl)methanes 73 and 74, in 79% and 94% yields, respectively. Reduction of 73 with LiAlH4 in a very high boiling solvent (C30H50 squalene) in a two-phase system with a phase transfer catalyst leads to the tetrakis(germyl)methane 75 in 20% yield. A substantial quantity (18% yield) of 76, the tris(germyl) analog, is also obtained as a by-product. The reduction of 74 with LiAlH4, under conditions similar to those for the reduction of 73, leads to compounds 75 and 76 in 1:1 molar ratio in approximately 12% yield each (Scheme 25) <1998JA6738>.

CBr4

GeX2Br

4GeX2·diox Toluene

BrX2Ge

GeH3

LiAlH4

GeX2Br GeX2Br

73, X = Cl

H3Ge

GeH3 GeH3 75

74, X = Br

Scheme 25

GeH3 +

H GeH3

H3Ge 76

221

Functions Containing at Least One Metalloid (Si, Ge, or B)

A more attractive synthesis of the trigermylmethane 76 is based on the direct reduction of tris(tribromogermyl)methane. The bromide 77 in turn is prepared by direct insertion of GeBr2 into the CBr bonds of bromoform (Scheme 26) <1996CM2491>. Br Br

GeBr3

3GeBr2.diox Br

Toluene, 85 °C

Br3Ge

GeH3

LiAlH4

GeBr3

H3Ge

15%

GeH3

89% 77

76

Scheme 26

Trigermylmethane 76 is a stable, colorless liquid, and its relatively high volatility makes it highly suitable for low-pressure chemical vapor deposition experiments <1999MI958>. The structure of this compound was determined by electron diffraction and density functional theory calculations <1999JST29>.

6.06.2.1.4

Functions bearing mixed metalloids

There are several methods for the production of compounds of the general structure RC(E1Xm) (E2Xn) (E3Xmn), where E1, E2, and E3 = Si, B, or Ge, but three groups of reactions are most important: (i) synthesis based on -silyl-, boryl, or germyl-substituted organometallics; (ii) synthesis based on p-bonded low-coordinate boron and germanium derivatives; and (iii intermolecular C–H insertions and cyclization reactions involving a stable germylene.

(i) Synthesis based on a-silyl-, boryl-, or germyl-substituted organometallics This approach has been extensively studied and seems to be most general for preparing functions bearing mixed metalloids <1995COFGT(6)171>. An example provided in Equation (8) illustrates the application of this strategy for the synthesis of base-stabilized germylene containing a Si2(GeII)C function <1997OM2116, 1999OM389>.

N Li

TMS TMS

GeCl2.diox Et2O, –78 °C 53%

TMS TMS

N

ð8Þ

Ge TMS TMS

N

Wiberg and co-workers have investigated the reaction of (Me3Ge)2CHLi with But2Si(H)F, which gives the sterically overloaded digermylsilylmethane 78 <1996JOM(511)239>. With bromine, 78 reacts, as do hydrosilanes, to form bromosilyl derivative 79. Coupling reaction between 79 and MeLi followed by the treatment of a lithium intermediate 80 with MeOH lead to the silyldigermylmethane 81 (Scheme 27). Li Me3Ge

GeMe3

Bu2t SiHF

Me3Ge

12 h, 130 °C

Me3Ge

But Si But H

77%

Br2

Me3Ge

CCl4, 0 °C 95%

Me3Ge

78

MeLi THF, –78 °C

Me3Ge Me3Ge Li

But Si But Me

But Si But Br 79

SiMeBut2

MeOH 95%

Me3Ge

GeMe3 81

80

Scheme 27

222

Functions Containing at Least One Metalloid (Si, Ge, or B)

Silylation of 2-trimethylsilylboratabenzene salt 83 affords compounds 84 and 85 as a slowly interconverting equilibrium mixture of isomers (Scheme 28). When this reaction was run in THF, a mixture of the monosilylated compound 82, the expected bis(trimethylsilyl) derivatives, and more highly silylated species were formed. When pentane was used as the reaction medium, the chemoselectivity was much improved. The product obtained was essentially an equilibrium mixture of the isomers 84 and 85 in a 4:3 ratio with some 82 (10–20%) <1997OM926>.

B Me

LDA THF, 1 h,

TMS

92%

82

TMS

TMS B TMS Me

TMS–Cl

Li B Me

Pentane, rt 72%

83

+

TMS

B Me

TMS

85

84

Scheme 28

Structurally related 1-chloro-1,2-dihydroborinines 88 and 89 were prepared according to the pathway outlined in Scheme 29. Treatment of stannacyclohexadiene 86 with lithium diisopropylamide (LDA) followed by chlorotrimethylsilane affords stannacycle 87 in excellent yield. Transmetallation through reaction of 87 with BCl3 then provides boracyclohexadienes 88 and 89 <1997JOC8286>. TMS

i. LDA

TMS

ii.TMS– Cl

BCl3

90%

–Bu2SnCl2

Sn Bu

TMS

Sn Bu

Bu 86

TMS B Cl

55–60%

Bu

+ TMS

TMS

88

87

B Cl

TMS

89

Scheme 29

(ii) Synthesis based on p-bonded low-coordinate boron and germanium derivatives The scope of these reactions is restricted to the preparation of specific polyfunctional compounds. Thus, reaction of methyleneborane 90 with trimethylstannylethyne 91 affords the spiro cyclic compound 92, which upon isomerization followed by rearrangement gave compound 93. Lithium exchange of the latter with ButLi followed by treatment with chlorotrimethylsilane result in the formation of the cyclic compound 94 containing an B2SiC function (Scheme 30) <1994AG(E)2064>.

Dur TMS

B

B

Dur +

Me3Sn

Ar

TMS –20 °C

91

TMS

Dur B

TMS Me3Sn

90

Dur B Ar

92

TMS C

Dur B SnMe3 B Ar Dur

TMS

Bu

tLi

Dur B Li

TMS C TMS

93

B Ar Dur

TMS–Cl

Dur B TMS

TMS C

B Ar Dur

TMS

94

Ar = 3,5-Bu2t C6H3, Dur = 2,3,5,6-Me4C6H

Scheme 30

Functions Containing at Least One Metalloid (Si, Ge, or B)

223

The tetracoordinate germanium derivative 96 is reported to be formed by intramolecular cyclization of 1-germaallene 95 (Equation (9)) <1998CL811>.

H TMS

Tbt Ge C Tbt

Benzene, 80 °C

Ge

TMS

Tbt

ð9Þ

CH(TMS)2 (TMS)2HC

95

96 Tbt = 2,4,6-[(TMS)2CH]3C6H2

Diels–Alder and ene reactions of the germaethene Me2Ge = C(TMS)2 generated as a reaction intermediate by thermolysis of Me2GeCl-CLi(TMS)2 <1996ZN(B)838> or cycloadduct of the germaethene and anthracene <2000CJC1412> lead to various cyclic compounds containing an Si2GeC function <1996ZN(B)838>. Similarly, thermolysis of But2SiF-CLi(GeMe3)2 at 100 C in benzene and in the presence of propene, isobutene, butadiene, or 2,3-dimethylbutadiene leads to ene reaction products and/or [4+2]-cycloadducts of the germaethene Me2Ge = C(GeMe3) (SiMe2But2) 97 which contain a SiGe2C unit (Scheme 31) <1996JOM(519)107>. Me Me Ge

GeMe3 SiMe2But H

Me Ge Me

89%

GeMe3 SiMe2But

77%

Me GeMe3 Me Ge SiMe2But

97

Me Me Ge

GeMe3 SiMe2But H

97 73%

Me Me Me Me Me3Ge Ge Ge GeMe3 Bu2t MeSi

SiMe2But2

Scheme 31

(iii) Intermolecular CH insertions and cyclization reactions involving a stable germylene A great deal of chemical research has focused upon CH and CHal insertions and cyclization reactions involving divalent germylenes in the hope of developing general methods for introducing functionality into a variety of organic molecules <1996OM741, 1997AG(E)2514, 1996JOM(521)387, 1999JA4229>. Banaszak Holl and co-workers demonstrated that bis[bis(trimethylsilyl)methyl]germylene 98 inserts into the -CH bond of acetonitrile in the presence of THF and LiCl, MgCl2, or LiBr to yield 99 quantitatively as monitored by nuclear magnetic resonance (NMR) spectroscopy. Similar reactivity was observed for propionitrile, phenyl acetonitrile, and succinonitrile (Scheme 32). The presence of THF and specific salts was essential for the insertion reactions. For acetonitrile, no reaction occurred over the period of a week at 20 C when benzene, diethyl ether, or 1,4-dioxane were used as solvents in the absence of added salts. However, when 0.5 equiv. of THF was added to the reaction mixture in benzene, the reaction slowly proceeded to 5% completion after 3 days at 20 C. The reaction rate was dramatically affected by added salt. In THF solvent, the reaction is complete with 2 min and 20 min, respectively, if 0.2 equiv. of MgCl2 or LiCl are added <2001JA982>. It has also been found that by the reaction of germylene 98 with an excess of trans-1,2dichloroethene, cis-1,2-dichloroethene, or 1,1-dichloroethene, the [(TMS)2CH]2ClGe-functionalized ethenes 100, 102, and 104 can be obtained in quantitative yields <1996JOM(521)387>. The stereochemistry of the starting material was retained in the product, showing that these reactions proceeded stereospecifically. When 2 molar equiv. of 98 were used with 1,2-dichloroethenes, the reactions gave the double germylene insertion products 101 and 103 (Scheme 33).

224

Functions Containing at Least One Metalloid (Si, Ge, or B) TMS

TMS H

TMS Ge TMS

TMS

TMS

PhCH2CN

Ge

Ge

TMS

CN

H

TMS

MeCN

TMS

CN

TMS

TMS Ph

TMS 99

98

NC(CH2)2CN

MeCH2CN

TMS

TMS H

TMS

H

TMS

Ge TMS TMS

Ge TMS

CN CN

CN TMS Me

Scheme 32 TMS Cl

R2Ge Cl

Cl

TMS

rt Cl

Ge

TMS TMS

R2Ge

TMS TMS

Reflux

Ge

Cl

rt

Cl

Cl

TMS TMS

101

TMS R2Ge

Ge

TMS

100

Cl

TMS

TMS

TMS

Cl

Cl

TMS TMS

Ge

TMS 102

R2Ge Reflux

TMS TMS

TMS TMS Cl Cl Ge Ge TMS

TMS TMS TMS

103

TMS Cl Cl

R2Ge rt

Cl

TMS TMS

Ge

TMS 104 R = CH(TMS)2

Scheme 33

A stable digermacyclobutane 106 bearing (TMS)2CH groups at germanium atoms was obtained by the interaction of 98 with ethylene (Scheme 34). This reaction presumably runs via the germirane intermediate 105. An attempt to prepare the corresponding digermacyclobutanes by the reaction between 98 and propene or 2-butene was unsuccessful. Nevertheless, the digermacyclobutane 106 is a useful synthon for novel organogermanium compounds. For example, photolysis of 106 in carbon tetrachloride afforded 1,4-digerma-1,4-dichlorobutane 107 quantitatively, and photolysis in 2,3-dimethylbutadiene yielded 1-germacyclopent-3-ene 108 <1995OM2139>. The photolysis of 106 in a toluene solution of C60 provided the germylene and germacyclopropane adducts of C60, respectively. The former is possibly the first example of a closed [6,5]bridged derivative of germacyclopropane, while the latter is a closed [6,6]-bridged fullerene derivative of germacyclopentane <2001JOM(636)82>. Heterocyclic GeIVO species including a conjugated triene system and Si2CHGe functions have been obtained from the reaction of 98 with phenones. For example, germylene 98 reacts with benzophenone in THF at ambient temperature to produce compound 109. A number of other phenone species yield products similar to 98 and benzophenone. The reaction occurs with both weakly electron-withdrawing and releasing groups present on the rings. Moreover, the pattern of

225

Functions Containing at Least One Metalloid (Si, Ge, or B) TMS

TMS TMS

H Ge

TMS TMS

H

98

+

TMS

H

TMS TMS

TMS

H

Ge

TMS

TMS TMS Ge Ge TMS

TMS

TMS 105

106

98

TMS TMS TMS

Cl Ge

Ge Cl TMS TMS

TMS

TMS

TMS TMS CCl4

TMS TMS

106

TMS

hν

hν

Ge

TMS

–H2C=CH2 108

107

Scheme 34

reactivity of the 4,40 -dichlorobenzophenone and benzophenone imine resembles that of the benzophenone. In each case, rather than undergoing insertion, the germylene instead exclusively activates the aromatic ring, forming compounds 110 and 111 (Scheme 35) <2002OM457>.

TMS TMS

TMS TMS

PhCOPh

Ge

TMS O

Ge TMS

TMS

Ph

TMS 98

109 Cl

C O

Cl

PhC(=NH)Ph

TMS TMS

TMS Ge

TMS

NH Ph

TMS TMS

TMS Ge

O

TMS

Cl

Cl 111

110

Scheme 35

(iv) Miscellaneous The exhaustive hydroboration of the (CC)-groups in dimethyl-di-1-propynylsilane by adding Et2BH at room temperature is presumed to lead initially to the formation of a mixture of the threo- and erythro-3,3,5,6-tetrakis(diethylboryl)-4,4-dimethyl-4-silaheptanes 112. The erythro-112 reacts further by borane catalyzed intermolecular condensation to substituted disilatetraboratricyclo[6.2.16,9]dodecane 113. In contrast, the erythro-112 undergoes intramolecular, thermal elimination of Et3B to give the 1,2-diethyl-2,4-bis(diethylboryl)-3,3,5-trimethyl-3-silaborolane 114 (Scheme 36) <1995ZN(B)439>. Thermolysis of the silole 115 in a sealed evacuated tube without solvent at 175 C quickly and quantitatively resulted in the formation of the 2,4-disila-1-germatricyclo[2.1.0.02.5]pentane 116. The tricyclic skeleton of 116 incorporates the two fused three-membered ring comprising all different group 14 elements: C, Si, and Ge (Equation (10)) <2002JA9962>.

226

Functions Containing at Least One Metalloid (Si, Ge, or B) Me

Me Si

Me

SiMe2R BEt2

H Et2B

Me

+

H

Et2B

Me

Et Me

Et B

Me

–4Et3B

Si

B

Me

BH

Me

Et2B Me

B

Et H H Et Si Me Me

Et

B H

113

R = Et(Et2B)2C

–Et3B

Me Me Si H BEt2

H H

Et B Et

H Me

erythro -112

threo -112

BH

SiMe2R H

Et2B

Et

114

Scheme 36

R R Si

R

R Si 175 °C, 10 mm

Ge

H Si R

R Si Ge

Ph

R 115

Ph

R

ð10Þ

116

R = ButMe2Si

6.06.2.2

Functions Containing Metalloids and Metals

The work on functions RC(EXm)n(MLk)3n (E = Si, Ge, or B; M = metal; R = H or organyl; X = any substituent; n = 1 or 2) up to 1994 has been reviewed <1995COFGT(6)171>, and an account up to 1996 on compounds of elements of groups 11–13 containing (TMS)3C, (PhMe2Si)3C, and related ligands can be found <1996CCR125>. A review of the synthesis and reactions of compounds [(TMS)2CH]2E-E[CH(TMS)2]2 (E = Al, Ga, or In) contains much that is relevant to this chapter <1997CCR1>. Thus, this section considers in general, besides a number of fundamentals, the literature for 1997–2003.

6.06.2.2.1

Functions bearing silicon(s) and metal(s)

Synthesis of compounds of the general formula RC(SiX3)n(MLk)3n, where n = 2 or 1, is made by one of the following methods, which are mainly based on the standard synthetic procedures developed for the preparation of organometallic species: (i) metal–hydrogen exchange reactions of silylmethanes with basic metal-containing reagents; (ii) metal–halogen exchange reactions or oxidative metallation of halo(silyl)methanes; (iii) organometallic addition to vinyl silanes; (iv) synthesis via (cyclo)addition to stannaethenes; and (v) transmetallation of an already -metalated organosilanes. Most of the work in the decade 1993–2003 in this area has centered on the synthesis of specific organometallic derivatives, often with the goal of preparing new kinetically stabilized species.

227

Functions Containing at Least One Metalloid (Si, Ge, or B) (i) Metal–hydrogen exchange

In order to assess the potential utility of various possible metallating reagents, Seyferth and Lang carried out studies of the metallation of Me3SiCH2SiMe3, (Me3SiCH2)2SiMe2, (Me3Si)2CHSiMe2CH2SiMe3, and cyclo-(Me2SiCH2)3, using several strong organometallic bases such as ButLi/TMEDA, BusLi/TMEDA, BunLi/ButOK, and BunLi/ButOK/TMEDA <1991OM551>. BunLi/ButOK was found to be the most effective metallation reagent for CH2 groups in an SiCH2Si environment. The yields of monolithium derivatives in these reactions are very good, but further metallation did not occur even when a fivefold excess of the reagent was used. The bis(triethoxysilyl)methyl lithium 117 is simply prepared by treatment with t-butyllithium of the corresponding disilylmethane (Equation (11)). This compound is a very convenient starting material for a variety of common disilylmethane derivatives <1998JOM(562)79>. ButLi

Si(OEt)3

Si(OEt)3 Li

THF, –65 °C

Si(OEt)3

Si(OEt)3

ð11Þ

117

The 1,8-silanonaphthalene 118 has been used to generate uniquely the lithiodisilylmethane 120 as indicated in Scheme 37. The addition of MeLi to 118 presumably affords ring-opened 1-(8-silylnaphthyl)lithium 119, which undergoes proton migration leading to 120, a useful anion synthon <2000OM5582>.

TMS

Si

TMS

TMS

MeLi THF, rt

TMS Me Si Li

TMS

TMS

Me Si

118

Li

TMS TMS–Cl 46%

TMS

Me Si

TMS

120 119

Scheme 37

Lithiation of 2-[bis(trimethylsilyl)methyl]-6-methylpyridine with n-butyllithium yields lithiocarbanion 121, which reacts readily with chlorosilanes such as HSiCl3, MeSiCl3, Me2SiCl2, and Me3SiCl to form the corresponding hypervalent five-coordinate silicon species 122 (Scheme 38) <2000OM4437>.

Me

N

TMS

BunLi THF, 0 °C

Me

N Li

TMS

TMS TMS

121

XYZSi–Cl –78 °C

Me

N Y Si X Z

TMS TMS

122a–d a, X = H, Y = Z = Cl (79%) b, X = Me,Y = Z = Cl (72%) c, X = Y = Me, Z = Cl (94%) d, X = Y = Z = Me (78%)

Scheme 38

(ii) Metal–halogen exchange Bis(dimethylphenylsilyl)bromomethane, (Me2PhSi)2HCBr, has been reported to react with n-butyllithium in ether to give (Me2PhSi)2HCLi. The compound was isolated as solvent-free crystals and studied by multinuclear NMR and X-ray crystallography <1997OM4728>.

228

Functions Containing at Least One Metalloid (Si, Ge, or B)

By analogy with the preparation of bis(iodozincio)methane from diodomethane and zinc, the reaction of silyl-substituted dibromomethanes, RMe2SiCHBr2 (R = Me, Ph, p-MeOC6H4), with zinc dust in the presence of a catalytic amount of lead in THF provides route to silyl-substituted bis(bromozincio)methanes, RMe2CH(ZnBr)2 (72–80% yield) <1998SL1315>. Yet another example of the diversity of the original reagents, which may be used to synthesize lithiodisilylmethanes by metal–halogen reactions is the interaction of polysilacyclohexanes containing pseudohalogen (PhS) groups with lithio radical anion (see Schemes 14 and 16) <2000JOM(611)12>.

(iii) Organometallic addition to vinyl silanes The reactivity of 1,1-bis(trimethylsilyl)ethane 123 toward lithium metal has been re-investigated by Maercker and co-workers <1998EJO1455>. In THF, the exclusive formation of the product of reductive dimerization 124 was observed. When hexane or diethyl ether was used as solvent, an almost quantitative yield of a 1:1 mixture of the two lithio derivatives 124 and 126 was isolated. Lithium hydride elimination from the 1,4-dilithioalkane 124 can be ruled out since mixtures of 124 and 126, once synthesized, were found to be stable. Presumably, 123 adds to 125, which may be generated as a by-product, with formation of 126. In contrast to 123, 1,1-bis(trimethylsilyl)3,3-dimethyl-1-butene 127a reacted with lithium metal to give the 1,1-bis(trimethylsilyl)-1,2-dilithioalkane 128a, which shows no tendency to form a dimer product. The general reaction pathway was the same when the t-butyl group at the -position was replaced with a phenyl group (Scheme 39). TMS

2Li THF

TMS

Li TMS TMS

Li

123

2Li –LiH

124

–LiH

Hexane or Et2O

TMS

123

Li TMS

Li

TMS

TMS TMS

TMS

125

126

TMS TMS

TMS TMS

2Li R

THF

TMS TMS Li

127a

R Li

128a

127b

128b R = But (a), Ph (b)

Scheme 39

(iv) Synthesis via (cyclo)addition to stannaethenes The scope of these reactions, being investigated mainly by Wiberg and co-workers, has not yet been well delineated. Even so, the following useful procedures have been developed. Lithium organils (RLi) act as very active trapping reagents for Me2Sn = C(TMS)2 with formation of the adducts Me2Sn(R)-C(Li)(TMS)2. The insertion reactivity of RLi decreases when the bulkiness of R increases (decreasing reactivity in the order MeLi>BunLi>PhLi>ButLi; MeLi>(TMS)2CHLi>(TMS)3CLi). The influence of electronic effects is obviously smaller than

229

Functions Containing at Least One Metalloid (Si, Ge, or B)

those of steric effects (decreasing reactivity in the order (TMS)2(Me2ClSi)CLi>(TMS)2(Me2BrSi)CLi>(TMS)3CLi) <2000JOM(598)292>. Reactions of the stannaethene 129 with butadiene and propene as well as their methyl and phenyl derivatives afford Diels–Alder adducts and ene products containing an SnC(TMS)2 unit (Scheme 40). The reactions are accelerated by an increasing tendency of substituents in butadiene or propene to donate electrons and retarded by increasing bulkiness of substituents in 1,4- or 1,3positions. It is concluded that Diels–Alder and ene reactions of 129 occur in a concerted way and are orbital controlled <1998CEJ2571, 2000CJC1412>. Me TMS Me Sn TMS

100 °C, 2 days

Me Sn Me

Me TMS Me Sn TMS

TMS 100 °C, 3 days

TMS

129 Me TMS Me Sn TMS

100 °C, 2 days

Me TMS Sn Me TMS

+ 84:16

Scheme 40

(v) Transmetallation reactions A convenient route to bis(trimethylsilyl)methyl-substituted organoaluminum compounds is via transmetallation reactions starting from [(TMS)2CH]2Zn and aluminum halides. For example, compound 130 was prepared in high yield from the reaction depicted in Scheme 41. Compound 130 was reacted with Na/K alloy, which results immediately in the formation of organoalanes 131 and 132 due to a disproportion reaction <2001MI225>.

TMS

TMS +

Zn TMS

TMS Cl Cl Al Al Cl Cl TMS TMS

TMS 2AlCl3 Hexane, rt, 48 h

TMS

72%

130

Na /K

TMS TMS

TMS Al

TMS

TMS TMS 131

TMS + Cl

TMS Al Cl Cl

K +

Al

132

Scheme 41

The alkyl transferring properties of [(TMS)2CH]2Zn toward transition metal halides have also been studied. The monosubstituted tantalum halides, (TMS)2CHTaX4 (X = Cl, Br), were prepared by the reaction of TaX5 with [(TMS)2CH]2Zn in hexane <1999OM832>. Compounds

230

Functions Containing at Least One Metalloid (Si, Ge, or B)

(TMS)2CHTiCl3, (TMS)2CHNbCl4, and (TMS)2CHNbBr4 have been isolated, respectively, from reacting TiCl4, NbCl5, and NbBr5. In addition, the fluoride derivative (TMS)2CHNbF4 was prepared via chlorine–fluorine metathesis employing Me3SnF as a fluorinating reagent. The crystal structure of (TMS)2CHNbCl4 was determined by single-crystal X-ray diffraction <2001JOM(621)310>. The first bis(trimethylsilyl)methyl-substituted organogallium compound containing a GaGa single bond, 133, was synthesized by Uhl and co-workers according to Scheme 42 <1989JOM(364)289>. Remarkably, this compound reacted with tropolone by replacement of two (TMS)2CH groups and retention of its GaGa single bond <2002ZN(B)141>. As a starting compound for the synthesis of an alkylgallium-bridged [1,1]-ferrocenophane 135 Uhl and co-workers employed the trichloroalkylgallate 134, which is easily available by the reaction of GaCl3 with (TMS)2CHLi in THF (Scheme 43). Treatment of the adduct 134 with 1,10 -dilithioferrocene in hexane afforded the orange-red compound 135 in 47% yield <2001JOM(637/639)300>.

TMS

Li Ga2Br4.2 diox +

TMS

TMS O TMS O TMS TMS OH O Ga Ga O Ga Ga TMS TMS Pentane, –70 °C TMS O TMS 83% TMS TMS TMS

TMS

133

Scheme 42

GaCl3

+

(TMS)2CHLi

THF/Et2O, –10 °C 62%

[Cl3Ga-CH(TMS)2] [Li(THF)] 134

Fe[CpLi(TMEDA)]2 THF, –80 °C

TMS

TMS Ga Fe

Fe Ga TMS

TMS 135

Scheme 43

The transmetallation of the bridged ditin compound 136 with (TMS)2CHLi afforded a new organotin derivative 137, which was converted into its tetrachloro derivative 138 by stepwise reaction with Me2SnCl2 and SnCl4 (Scheme 44) <1998OM4096>. Along with this, the di- and trimethylene-bridged ditin compounds, 140 and 141, were prepared by reaction of 139 with (TMS)2CHLi followed by treatment with mercuric chloride (Scheme 45) <1998OM4096>. The synthetic potential of lithium bis(trimethylsilyl)methanide in transmetallation reactions is also illustrated by the synthesis of electron-deficient monocyclopentadienylvanadium(III) dialkyl 142 <1993OM2268> and vanadium(III) hydrocarbyl 143 <1999JCS(D)3345> (Equations (12) and (13)). These results provide a further demonstration that the bulky (TMS)2CH ligand may stabilize unusual metal complexes.

231

Functions Containing at Least One Metalloid (Si, Ge, or B) Me Me Me Cl Sn Sn Cl Me Me Me

Me Me TMS TMS Me 2Me2SnCl2 Sn Sn 110–120 °C, 30 h TMS Me Me Me TMS

2(TMS)2CHLi Pentane, 20 °C 82%

136

TMS TMS

137 Cl Me Cl TMS Sn Sn Me Me Me TMS

SnCl4

TMS

60–70 °C, 12 h

TMS

Cl Me Cl Sn Sn Cl Me Cl

TMS TMS

74% 138

Scheme 44

TMS

TMS F

TMS

TMS SnPh2

X SnPh2

SnPh2

2(TMS)2CHLi Pentane, 20 °C

F

SnCl2

4HgCl2

X

X

73–87%

SnPh2

SnCl2 TMS

TMS

TMS

TMS

139

141

140 X = (CH2)n; n = 2 or 3

Scheme 45

CpVCl2(PMe3)2

+

TMS

2 (TMS)2CHLi Et2O, 0 °C 90%

TMS

TMS TMS N Li N Cl N V V + 2 TMS TMS N Cl N N TMS TMS TMS

V

ð12Þ

TMS TMS 142

TMS Toluene, –78 °C 60%

TMS

TMS N TMS N V N TMS TMS

ð13Þ

143

Neutral alkyl derivative lanthanides, stabilized by bis(trimethylsilyl)groups, are, of course, known and interpretation of their stability in terms of steric protection appears to be generally accepted <1994CC2691, 1995JCS(D)3933>. Alkyl lanthanide complexes are the precursors of organolanthanide hydrides by hydrogenolysis of the lanthanidecarbon -bond. Bis(trimethylsilyl)methyl lanthanides are especially often used because they are usually hydrocarbon-soluble unsolvated species that can be straightforwardly obtained by reaction of organolanthanide halides with (TMS)2CHLi. The synthesis of 146 and 147 illustrates this. The crude products from the reaction of [LnCl3(THF)x] (Ln = Nd, Sm) with 2,3,4,5-tetramethylphospholylpotassium, 144 and 145, reacted smoothly with (TMS)2CHLi to give bis(trimethylsilyl)methyl derivatives 146 and 147 in fair-to-good yields (Scheme 46). [(C4Me4P)2LaCH(TMS)2] was also obtained by the same procedure, but the yields were very low and inconsistent <1999EJI1041>. Lanthanide metallocene cation [(C5Me5)2Sm][BPh4], which may be prepared from (C5Me5)2Sm and AgBPh4, reacts with (TMS)2CHLi in benzene to produce (C5Me5)2SmCH(TMS)2 in over 96% yield. [(C5Me5)2Nd][BPh4] similarly reacts with (TMS)2CHLi to produce (C5Me5)2NdCH(TMS)2 in quantitative yield <1998JA6745>.

232

Functions Containing at Least One Metalloid (Si, Ge, or B)

[LnCl3(THF)x]

2C4Me4PK

[(C4Me4P)2LnCl2K]

THF/Et2O

(TMS)2CHLi 53–67%

P Ln P

TMS TMS

144, Ln = Sm

146, Ln = Sm

145, Ln = Nd

147, Ln = Nd

Scheme 46

6.06.2.2.2

Functions bearing boron(s) and metal(s)

Important methods for the preparation of polyheteroatom species of the general formula RC(BX2)n(MLm)3n, where n = 1 or 2, M is metal, and R = H, alkyl, or aryl, along with some representatives examples, are summarized in Scheme 47. These comprise reactions: (i) via metal– hydrogen exchange (deprotonation of diorganoboranes and related compounds); (ii) via transmetallation; (iii) via cleavage of 1,1-diboryl- and 1,1,1-triboryl compounds; and (iv) via addition to vinyl boranes and methyleneboranes. During the years from the publication of chapter 6.06, COFGT (1995) to the end of 2003, little further effort was given to expanding this chemistry. Readers are referred to the reference <1995COFGT(6)171> and review <1991COS(1)487> for more detailed information concerning synthetic potential of the mentioned methods. A unique method for the synthesis of compounds containing a BSn2C function utilizes the reaction of the bicyclic N-pyrrolylborane 148 with bis(trimethylstannyl)ethyne <1997JOM(545/546)297>. The interaction of 148 with 2 equiv. of Me3SnCCSnMe3 proceeds selectively to give 149, in which the five-membered ring in 148 has been extended by two carbon atoms (Scheme 48).

6.06.2.2.3

Functions bearing germanium(s) and metal(s)

In contrast to the numerous reactions involving metallation of CH2 groups in an SiCH2Si environment, the metal–hydrogen exchange reactions have met with very limited success when applied to the corresponding germyl analogs <1995COFGT(6)171>. The metal–halogen exchange reactions seem to be less limited than the direct metallation of organogermanes. Thus, Wiberg and co-workers have described an efficient route to lithium bis(trimethylgermyl)methide 151 starting from bromoform (Scheme 49). This approach permits access to bis(trimethylgermyl)bromomethane 150, which is difficult to obtain by other methods and produces salt-free reagent 151 in good yield. The ease with which the latter is prepared makes it a particularly attractive starting material for a variety of organic and inorganic applications. The reactivity of 151 appears roughly comparable to that of (TMS)2CHLi <1996JOM(511)239>. Triethylgermyl-substituted bis(bromozincio)methane, Et3GeCH(ZnBr)2, has been prepared from the corresponding dibromide by Pb-catalyzed reaction with zinc dust in THF (30–40% yield) <2000SL495>.

6.06.2.2.4

Functions bearing mixed metalloid(s) and metal(s)

Very few species with this special ligand arrangement around the carbon atom have been reported up to the end of 2003. In practice, they can be prepared by multiple-step procedures involving reactions described in Sections 6.06.2.2.1–6.06.2.2.3. In particular, if mixed compounds such as XnE1CH2E2Ym or XnE1CH(Hal)E2Ym are available then metal–hydrogen or metal–halogen exchange reactions seem to be the most practical route to metallated derivatives. Another attractive and potentially general route to functions with mixed metalloid(s) and metal(s) is provided by the reactions of heteroalkenes with organometallics. Some examples taken from the literature are illustrated by Equations (14)–(17).

233

Functions Containing at Least One Metalloid (Si, Ge, or B) Approaches to Forming Stable RC(BX2)n(MLm)3–n Species Via metal–hydrogen exchange

Mes2B

BMes2

K

KH THF

Mes2B

BMes2

<1982JCR(S)132>

Via transmetallation reaction Li B O O

O B O

PbPh3

Ph3PbCl

B O O

O B O

THF/ether

<1976JOM(110)25

Via cleavage of 1,1-diboryl- or 1,1,1-triboryl compounds

SnPh3 B O O

O B O

SnPh3

MeLi O B O

THF, –78 °C

Li

<1976JOM(110)25>

O

B

O B O O

O B O

Li

MeLi

B O O

O B O

THF, –70 °C <1973JA5096>

Via addition to vinylboranes and methyleneboranes But

But TMS

Cl

TMS

Cl

TMS TMS K

K /Na THF

But

But K

<1985AG(E)788>

Mes

Mes Li+ C B TMS TMS

2ButLi

Mes

Mes 2Li+ B C B t t Bu Bu –

–

<1988AG(E)1370>

Scheme 47

Li CpH

But

But B B Mes Mes

234

Functions Containing at Least One Metalloid (Si, Ge, or B) Me3SnC SnMe3 N B

Me3SnC SnMe3

C6D6, rt

B

Et

Et

Me3Sn

148

SnMe3

B

Et Me3Sn

B Et Me3Sn

SnMe3 SnMe3 SnMe3

SnMe3

SnMe3

Me3Sn 149

Scheme 48

Br Br

Br

Me3GeCl, 2BunLi Br

THF, –78 °C 85%

Me3Ge

Li

BunLi GeMe3

Et2O, –78 °C

Me3Ge

150

GeMe3 151

Scheme 49

Li But Si But H

But Si But H

MeLi THF

GeMe3

GeMe3

ð14Þ

<1996JOM(511)239> Li TMS

B O

LiTMP THF

O

TMS

B O

O

ð15Þ

<1983OM230, 1991COS(1)487>

Li+

– B Me

TMS

Me3SnCl

SnMe3 B TMS Me

Pentane, rt

+

Me3Sn

B Me

TMS

ð16Þ

<1997OM926> BMes2 TMS

RM

R

M BMes2 TMS

ð17Þ R = Bun, But, Ph, (R1S)2CH, ButO2CCH2, CH2=CH(CH2)4, Bu2nCu(CN) <1987JA931, 1991COS(1)487>

235

Functions Containing at Least One Metalloid (Si, Ge, or B) 6.06.3

FUNCTIONS CONTAINING THREE METALS

In contrast to sp2- <2000CRV2887> and sp3-1,1-bismetallic derivatives <1996CRV3241>, which have been intensively studied in the late 1990s and early 2000s, the chemistry of functions RC(MLk)(M1Ll) (M2Lm) (M, M1, M2 = metal) featuring three -bonds between carbon and metal atoms is in its infancy. Although several structural types of sp3-geminated trismetallics are known, information about these compounds remains sparse. Little further effort has been given to expanding this chemistry since the publication of COFGT (1995). This chapter therefore presents an illustrative summary of the methods used for the preparation of 1,1,1-trismetallic derivatives. Methods for preparing specific types of compounds were discussed previously <1995COFGT(6)171>.

6.06.3.1

Three Similar Metals

Isolable compounds of the type RC(MLm)3 (M = metal) are known with M = Li, Hg, Al, Sn, and Pb. Table 1 outlines the synthetic approaches to these species with an example from each major method. The limits of the methods have certainly not been fully explored and, up to the end of 2003, comparatively little has been published on work devoted to the use of trimetallomethanes as reagents for organic synthesis.

Table 1 Preparation of organometallic species of the type RC(MLm)3

Method From halides: 1

2

From active C–H compounds: 3 4 From unsaturated compounds: 5

From organometallics: 6 7 8

Description Reductive metallation with lithium vapor Reductive displacement of halogen by metallate anions Lithium–hydrogen exchange Electrophilic mercuration Hydrometallation (M = Al, Sn)

Oxidative–reductive transmetallation Boron–mercury exchange Pyrolysis reactions

General equation

Preparation equation number

RCX3 + 6Li ! RCLi3 + 3LiX

(18)

RCX3 + 3ML m ! 3RC(MLm)3 +3X

(19)

FG-RCH3 + 3MR1 ! FG-RCLi3 +3R1H

(20)

FG-RCH3 + HgX2 ! FG-RC(HgX)3 + 3HX

(21)

+ 3MH

M M M

(22), (23)

RCM3 + 3M1 ! RCM13 + 3M

(24)

RC(BX2)3 + 3HgY2 ! RC(HgY)3 +3BX2Y

(25)

CHnLi4n ! CHLi3 + (n = 0–3)

(26)

The following tentative generalizations may be useful. (i) Direct halogen–metal exchange in polyhaloalkanes by treatment with reactive metal, such as Li or Mg, is only of limited value for the preparation of polymetalated methanes due to -elimination of metal halide after the first step being faster than the halogen–metal exchange. However, these difficulties can be overcome by high-temperature reaction of polyhaloalkanes with

236

Functions Containing at Least One Metalloid (Si, Ge, or B)

metal vapor (the Lagow procedure). This technique is especially suited for the preparation of organometallics of readily ionizable metals (Equation (18)).

Cl

Li

Li

Cl Cl

+ 6Li(g)

750 °C

Li

+

Li

Li

Li

+ Li

Li Li

Li 40%

16%

Li

+ 19%

ð18Þ

20%

<1983JOM(249)1>

(ii) The coupling reactions between chloroform and organostannyl- and organoplumbylmetallic compounds of the type R3MLi is the valuable route to the corresponding trimetallomethanes (Equation (19)). It is known that the metallate anions containing transition metals are among the strongest nucleophiles known to chemists. However, the synthetic potential of reactions between polyhaloalkanes and metallate anions of transition metals is not clear.

Cl Cl

PbPh3

Ph3PbLi Cl

THF, –60 °C 91%

Ph3Pb

PbPh3

ð19Þ

<1985CB380>

(iii) Much more easily accessible than the 1,1,1-trilithioalkanes are certain perlithioalkynes, for example perlithiopropyne (C3Li4), since alkyllithium reagents can abstract quantitatively not only the hydrogen atoms on sp-hybridized carbon atom, but also those of the adjacent methyl group (Equation (20)). Unlike alkynes, linear and branched alkenes upon treatment with organolithium reagents form only mono- and dilithiated derivatives. Typical saturated hydrocarbons are not acidic enough to form the polylithiated species by metal–hydrogen exchange with basic reagents. 4BunLi Hexane 75%

Li Li Li

Li

ð20Þ

<1984AG(E)995>

(iv) Metal–hydrogen exchange with Lewis acidic reagents, such as Hg(OAc)2, represents one of the most direct and convenient routes to 1,1,1-trimercurioalkane derivatives (Equation (21)). The method tends to fail, however, in cases where the CH bonds are not sufficiently acidic. Hg(OAc)2

MeCN

150 °C, 20 h

NC

HgOAc HgOAc HgOAc

93%

ð21Þ

<1974JPR557>

(v) The best way to 1,1,1-trialuminioalkanes involves bishydroalumination of alkynylalanes derived from the reaction of alkali metal acetylides with dialkylaluminum chlorides (Equation (22)).

Bun

2Et2AlH AlEt2

70 °C <1963BSF1462>

Bun

AlEt2 AlEt2 AlEt2

ð22Þ

237

Functions Containing at Least One Metalloid (Si, Ge, or B)

(vi) Transmetallation reactions with other elements of the periodic table for example boron/ mercury exchange (Equation (23)) can also be used for the synthesis of sp3 geminated trismetallics but the limits of the method have not been fully explored. B(OMe)2 (MeO)2B

HgCl

3HgCl2

B(OMe)2

ClHg

THF, rt 62%

HgCl

ð23Þ

<1983JOM(243)245>

(vii) A general route to 1,1,1-tristannylalkanes involves the hydrostannation of 1,1-distannyl1-alkenes (Equation (24)).

R

SnMe3

Me3SnH

SnMe3

52–80%

SnMe3 SnMe3 SnMe3

R

ð24Þ

R = Me, Bun, Ph, PhCH2, MeOCH2, PhOCH2, PhO <1985OM1044>

(viii) In practice, mercury–lithium exchange reactions represent one of the most effective routes to the trilithiomethanes (Equation (25)). Reactions using tin–lithium exchange would be even better than mercury–lithium exchange, but tris(trimethylstannyl)methanes are not easily available. HgCl ClHg

Li

Li THF, 20 °C

HgCl

Li

ð25Þ

Li

<1982MI47>

(ix) As a preparative method to be used in practical organic synthesis, pyrolysis reactions do not yet provide advantages over conventional methods. It shows high promise, however, as a method for preparing otherwise inaccessible species (Equation (26)). 225 °C CLi4

CLi4

8 min

20%

+

C3Li4

+

40%

C2Li4 30%

+

C2Li2

ð26Þ

10%

<1985JA5313>

6.06.3.2

Three Dissimilar Metals

A few of the compounds of the general formula HC(MLk)2(M1Lm) have been prepared by metallation or transmetallation reactions and examples are described in COFGT (1995) <1995COFGT(6)171>. The readily available trismetallics 152–155 <1983IZV636, 1980TCC109> may prove useful in the synthesis of other compounds having three dissimilar metals bonded to the same carbon; however, the synthetic potential of these species in transmetallation reactions remains unexplored. Li Ph3Sn

SnPh3 152

SnMe3

Li Ph3Pb

PbPh3 153

Ph3Pb

AlEt2 AlEt2 AlEt2

PbPh3 154

155

238

Functions Containing at Least One Metalloid (Si, Ge, or B)

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242

Functions Containing at Least One Metalloid (Si, Ge, or B) Biographical sketch

Vadim D. Romanenko was born in Lugansk, Ukraine, in 1946. He studied at the Institute of Chemical Technology, Dnepropetrovsk, Ukraine and received his Ph.D. degree there under the direction of Professor S. I. Burmistrov. Since 1975 he has been working at the National Academy of Sciences of Ukraine from which he earned his Doctor of Chemistry degree in 1988. He became a full professor in 1991. He has been a visiting scientist at the Centre of Molecular and Macromolecular Studies, Lodz, Poland, the Shanghai Institute of Organic Chemistry, China, the University of Pau & des Pays de l’Adour, France, the University Paul Sabatier, Toulouse, France, the University California Riverside, USA. His research interests include a wide range of topics at the border between organic and inorganic chemistry, in particular the chemistry of multiple bonded heavy main group elements. He is the author of approximately 260 papers on organoelement chemistry. He is also author of numerous reviews and two monographs on low-coordinated phosphorus compounds.

Valentyn Rudzevich was born in Kazatin, Ukraine, in 1968. He received his Diploma degree in 1992 from Taras Shevchenko Kiev State University, Ukraine. Since 1992 he has been working at the Institute of Organic Chemistry of National Academy of Science of Ukraine, from which he received his Ph.D. degree under the supervision of Professor V. D. Romanenko in 1997. Afterwards, he carried out postdoctoral studies at the Universite´ Paul Sabatier, Toulouse, France, University of California Riverside, USA and the Johannes Gutenberg University, Germany. On his return to Kiev, he joined the Institute of Organic Chemistry where he is presently a Scientist Researcher. His research interests are focused on organoelement compounds, short-lived intermediates, and coordination chemistry.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 205–242

6.07 Functions Containing Four Halogens or Three Halogens and One Other Heteroatom Substituent A. SENNING and J. Ø. MADSEN Technical University of Denmark, Kgs. Lyngby, Denmark 6.07.1 TETRAHALOMETHANES, C(Hal)4 6.07.1.1 Four Similar Halogens 6.07.1.1.1 Tetrafluoromethane 6.07.1.1.2 Tetrachloromethane 6.07.1.1.3 Tetrabromomethane 6.07.1.1.4 Tetraiodomethane 6.07.1.2 Three Similar Halogens and One Different Halogen 6.07.1.2.1 Trifluoromethyl halides 6.07.1.2.2 Trichloromethyl halides 6.07.1.2.3 Tribromomethyl halides 6.07.1.2.4 Triiodomethyl halides 6.07.1.3 Two Similar Halogens 6.07.1.3.1 Difluoromethylene dihalides 6.07.1.3.2 Dichloromethylene dihalides 6.07.1.3.3 Dibromomethylene dihalides 6.07.1.3.4 Diiodomethylene dihalides 6.07.1.4 Bromochlorofluoroiodomethane 6.07.2 METHANES BEARING THREE HALOGENS 6.07.2.1 Three Halogens and a Chalcogen 6.07.2.1.1 Three halogens and an oxygen function 6.07.2.1.2 Three halogens and a sulfur function 6.07.2.1.3 Three halogens and an Se or Te function 6.07.2.2 Three Halogens and a Group 15 Element 6.07.2.2.1 Three halogens and a nitrogen function 6.07.2.2.2 Three halogens and a phosphorus function 6.07.2.2.3 Three halogens and an As, Sb, or Bi function 6.07.2.3 Three Halogens and a Metalloid 6.07.2.3.1 Three halogens and a silicon function 6.07.2.3.2 Three halogens and a boron function 6.07.2.3.3 Three halogens and a germanium function 6.07.2.4 Three Halogens and a Metal Function 6.07.2.4.1 Trihalomethyl alkali and earth alkali metals, CHal3M (M = Li, Na, K, Cs, Mg) 6.07.2.4.2 (Trihalomethyl)aluminum, -gallium, -indium, and -thallium compounds, CHal3MRn (M = Al, Ga, In, Tl) 6.07.2.4.3 (Trihalomethyl)tin and -lead compounds, CHal3MRn (M = Sn(II), Sn(IV), Pb(IV)) 6.07.2.4.4 (Trihalomethyl)zinc, -cadmium, and -mercury compounds, CHal3MR (M = Zn, Cd,Hg(II)) 6.07.2.4.5 (Trihalomethyl)copper, -silver, and -gold compounds, CHal3MRn (M = Cu(I), Cu(III), Ag(I), Ag(III), Au(I), Au(III)) 6.07.2.4.6 Miscellaneous trihalomethyl transition metal compounds, CHal3MRn (M = transition metal)

243

244 244 244 244 244 244 244 244 245 245 246 246 246 246 247 247 248 248 248 248 251 257 258 258 260 261 261 261 262 262 263 263 263 263 263 264 264

244 6.07.1

Functions Containing Four Halogens or Three Halogens TETRAHALOMETHANES, C(Hal)4

6.07.1.1

Four Similar Halogens

All four compounds CF4, CCl4, CBr4, and CI4 are commercially available.

6.07.1.1.1

Tetrafluoromethane

Two Russian patents deal with the industrial preparation of CF4 by fluorination of activated carbon <2002RUP2181351> and of trifluoromethane <2002RUP2181352> with F2. According to a US patent, CF4 can be prepared by vapor-phase chlorofluorination of methane with Cl2 and HF in the presence of a catalyst such as CrO3 <1995USP5446218>. A similar process (fixed-bed reactor, reaction temperature 449 C) with trichloromethane as the starting material yields CF4 with 99.8% conversion and 29.1% selectivity <1997JAP09020695>.

6.07.1.1.2

Tetrachloromethane

The formation of CCl4 by chlorination of methane with Cl2 is catalyzed by nanocrystalline MgO or nanocrystalline CaO <2000JA5587>.

6.07.1.1.3

Tetrabromomethane

No further advances have occurred in this area since the publication of chapter 6.07.1.1.3 in <1995COFGT(6)211>.

6.07.1.1.4

Tetraiodomethane

No further advances have occurred in this area since the publication of chapter 6.07.1.1.4 in <1995COFGT(6)211>.

6.07.1.2 6.07.1.2.1

Three Similar Halogens and One Different Halogen Trifluoromethyl halides

(i) Chlorotrifluoromethane According to a US patent, the commercially available CClF3 is one of the products of the vaporphase chlorofluorination of methane with Cl2 and HF in the presence of a catalyst such as CrO3 <1995USP5446218>.

(ii) Bromotrifluoromethane The boiling point of CBrF3 is 59.0 C <2001MI897>. An industrial high-temperature process for the preparation of CBrF3 involves the treatment of CHF3 with Br2 in the presence of Cl2 <1995SUP1381923>. Bromotrifluoromethane, commercially known as Halon 1301, is being phased out as a consequence of the Montreal Protocol <1995MI8>.

Functions Containing Four Halogens or Three Halogens

245

(iii) Trifluoroiodomethane This compound is commercially available. A method for the preparation of CF3I is based on the treatment of solvated (trifluoromethyl)zinc bromide CF3ZnBr with ICl. The yield is 70% and complications with the onus of heavy metal containing wastes, typical of earlier methods, is also avoided <1994JFC(67)91>. A patented procedure for the preparation of CF3I calls for the interaction of pentafluoroethane with I2 in the presence of alkali metal or earth alkali metal salts <2000FRP2794456>. A flow reactor process carried out at 400 C in the presence of CuI converts a 1:1 iodine–trifluoroacetic acid mixture to CF3I <2001MI144>.

6.07.1.2.2

Trichloromethyl halides

(i) Trichlorofluoromethane This compound is commercially available. The fluorination of tetrachloromethane with HF in the presence of NH4AlF4 and -Al2O3 in a high-temperature reactor yields CCl3F as the main product <1990GE(E)P278473>. The cited patent is the latest in a series of closely related patents. Both trichloromethane and tetrachloromethane react slowly with XeF2 to form, inter alia, CCl3F <1993JFC(62)293>.

(ii) Bromotrichloromethane This compound is commercially available. It can be prepared with 45% yield from CHCl3 and CBr2F2 in the presence of Bu4NHSO4 and KOH <1998PLP173916>. The air labile cubic fullerene solvate C6012CBrCl3 and the air stable hexagonal solvate C6012CBrCl3 have been prepared as potential superconductors <2003CM288>.

(iii) Trichloroiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.2.2 in <1995COFGT(6)211>.

6.07.1.2.3

Tribromomethyl halides

(i) Tribromofluoromethane This compound is commercially available. No further advances have occurred in this area since the publication of chapter 6.07.1.2.3 in <1995COFGT(6)211>.

(ii) Tribromochloromethane A 43% yield of the commercially available CBr3Cl is obtained in the reaction of CBr2F2 with CHBr2Cl in the presence of benzyltriethylammonium chloride and KOH <1998PLP173916>.

(iii) Tribromoiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.2.3 in <1995COFGT(6)211>.

246 6.07.1.2.4

Functions Containing Four Halogens or Three Halogens Triiodomethyl halides

(i) Fluorotriiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in <1995COFGT(6)211>.

(ii) Chlorotriiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in <1995COFGT(6)211>.

(iii) Bromotriiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.2.4 in <1995COFGT(6)211>.

6.07.1.3 6.07.1.3.1

Two Similar Halogens Difluoromethylene dihalides

(i) Bromochlorodifluoromethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.1 in <1995COFGT(6)211>. Bromochlorodifluoromethane, formerly commercially available as Halon 1211, is being phased out as a consequence of the Montreal Protocol <1995MI8>.

(ii) Chlorodifluoroiodomethane A 9% yield of CClF2I (b.p. 31–34 C) is obtained (in admixture with other products) in the nickel catalyzed high-temperature reaction of commercially avavailable 2,2,3-trifluoro-3-(trifluoromethyl)oxirane (a convenient source of CF2 by thermally induced loss of (CF3)2C(¼O)) with ICl <1996JA8140>.

(iii) Bromodifluoroiodomethane A 9% yield of CBrF2I is obtained in the nickel catalyzed high-temperature reaction of 2,2,3trifluoro-3-(trifluoromethyl)oxirane with IBr <1996JA8140>.

6.07.1.3.2

Dichloromethylene dihalides

(i) Dichlorodifluoromethane Dichlorodifluoromethane (b.p. 28.0 C, <2001MI897>) is one of the minor products of the nickel catalyzed high-temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with ICl <1996JA8140>. Both CHCl3 and CCl4 react with XeF2 to form CCl2F2 <1993JFC(62)293>. The reaction of CCl4 with HF in the presence of an NH4AlF4 catalyst yields CCl2F2 as the minor product with CCl3F as the major product <1990GE(E)P278473>. The cited patent is the latest in a series of closely related patents.

Functions Containing Four Halogens or Three Halogens

247

(ii) Bromodichlorofluoromethane The b.p. of CBrCl2F is 52.5 C <2001MI897>. No synthetic advances have occurred in this area since the publication of chapter 6.07.1.3.1 in <1995COFGT(6)211>.

(iii) Dichlorofluoroiodomethane Dichlorofluoroiodomethane can be obtained by reaction of (dichlorofluoromethyl)tris(dimethylamino)phosphonium chloride [(Me2N)3P(CCl2F)]Cl with I2 or ICl <1982JFC(20)89>.

(iv) Bromodichloroiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.2 in <1995COFGT(6)211>.

6.07.1.3.3

Dibromomethylene dihalides

(i) Dibromodifluoromethane This compound is commercially available. A 68% yield of CBr2F2 (b.p. 25.0 C <2001MI897>) is obtained in the nickel catalyzed high-temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with Br2 <1996JA8140>. Dibromomethane reacts with XeF2 to form CBr2F2 <1993JFC(62)293>.

(ii) Dibromodichloromethane This compound is commercially available. A 51% yield of CBr2Cl2 is obtained in the reaction of CHBrCl2 with CBr2F2 in the presence of Bu4NBr and NaOH <1998PLP173916>.

(iii) Dibromochlorofluoromethane This compound is commercially available. No further advances have occurred in this area since the publication of chapter 6.07.1.3.3 in <1995COFGT(6)211>.

(iv) Dibromofluoroiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.3 in <1995COFGT(6)211>.

(v) Dibromochloroiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.3 in <1995COFGT(6)211>.

6.07.1.3.4

Diiodomethylene dihalides

(i) Difluorodiiodomethane Up to 78% yield of the commercially available CF2I2 is obtained in the nickel catalyzed high temperature reaction of 2,2,3-trifluoro-3-(trifluoromethyl)oxirane with I2, IBr, or ICl, respectively <1996JA8140>.

248

Functions Containing Four Halogens or Three Halogens

(ii) Dichlorodiiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.4 in <1995COFGT(6)211>.

(iii) Bromofluorodiiodomethane No further advances have occurred in this area since the publication of chapter 6.07.1.3.4 in <1995COFGT(6)211>.

(iv) Dibromodiiodomethane This compound is still unknown.

(v) Chlorofluorodiiodomethane This compound is still unknown.

(vi) Bromochlorodiiodomethane This compound is still unknown.

6.07.1.4

Bromochlorofluoroiodomethane

Both the racemic compound and the two enantiomers of bromochlorofluoroiodomethane CBrClFI have been considered in theoretical work <2000MI3811>, but no syntheses have been reported so far.

6.07.2

METHANES BEARING THREE HALOGENS

6.07.2.1 6.07.2.1.1

Three Halogens and a Chalcogen Three halogens and an oxygen function

(i) Trihalomethanols, CHal3OH (a) Trifluoromethanol. No new preparative procedures for CF3OH have become known. In an ion flow tube study, it was shown that CF3OH is formed from (trifluoromethyl)sulfur pentafluoride CF3SF5 and hydroxide anions <2003MI(223-224)403>. In the environment CF3OH appears to be formed in the upper atmosphere from trifluoromethoxy radicals and ambient hydrogen donors <2001CPL(345)435>. (b) Trichloromethanol. UV irradiation of methanolchlorinenitrogen gas mixtures generates, inter alia, CCl3OH, which again decomposes to C(¼O)Cl2 and HCl <2000CPL(322)97>. (c) Tribromomethanol. The acidity of the unknown CBr3OH has been investigated by quantum chemical methods <1995JPC12151>. All other CAS references to CBr3OH appear to be in error due to confusion with 2,2,2-tribromoethanol. (d) Dichlorofluoromethanol. Transient CCl2FOH is formed by insertion of 1D oxygen atoms into the CH bond of CHCl2F <1972JPC1425>. (e) Chlorodifluoromethanol. Transient CClF2OH is formed by insertion of 1D oxygen atoms into the CH bond of CHClF2 <1972JPC1425>.

Functions Containing Four Halogens or Three Halogens

249

(ii) Trihalomethyl ethers, CHal3OR 4-Amino- and 4-nitrophenol can be converted in 52–90% yield into the corresponding trifluoromethyl ethers CF3OAr by reaction with CCl4 or CCl3F in the presence of HF and one or several of the following catalysts: KF, NaF, SbCl3, SbCl5, SnCl4 TaCl5, TiCl4 <2001GEP10030090>. This is by and large a rediscovery of earlier findings along the same lines <1982JFC(19)553>. The aliphatic trifluoromethyl ethers CF3OCH2CF3 and CF3OCH(CF3)2 have been prepared by treatment of the corresponding alcohols with CCl4 and HF in the presence of a Lewis acid catalyst. The mixed trihalomethyl ethers CF2ClOCH(CF3)2 and CCl2FOCH(CF3)2 were also among the products <1995USP5382704>. 2-Methoxyaniline has been converted into 2-(trifluoromethoxy)aniline by protection of the amino group as an isocyanate (by treatment with C(¼O)Cl2), AIBN catalyzed chlorination of 2-methoxyphenyl isocyanate to 2-(trichloromethoxy)phenyl isocyanate (90% yield), halogen exchange with liquid HF at 100 C, and hydrolysis of 2-(CF3O)C6H4N¼C¼O to 2-(CF3O)C6H4NH2 <1998FRP2763940>. A particularly convenient and general method for the preparation of aliphatic and aromatic trifluoromethyl ethers CF3OR 8 has been found in the shape of the conversion of alcohols or phenols ROH 1 to the corresponding dithiocarbonates ROC(¼S)SMe 2, which in turn are converted into trifluoromethyl ethers CF3OR 8 by treatment with an N-halo imide such as 1,3dibromo-5,5-dimethylhydantoin and the commercially available 70% HF/pyridine reagent (Olah’s reagent), cf. Scheme 1. In the case of R = secondary or tertiary alkyl or ArCH2, the milder 50% HF/ pyridine reagent is required to prevent the formation of the corresponding fluoride RF. Typical examples of 8 thus prepared are 2-benzyloxy-1-bromo-3-(trifluoromethoxy)benzene 1-Br-3(CF3O)C6H4 (56% yield), methyl 3-(trifluoromethoxy)benzoate 3-(CF3O)C6H4C(¼O)OMe (76% yield), 4-acetoxy-40 -(trifluoromethoxy)biphenyl 4-[MeC(¼O)O]C6H4C6H4(OCF3)-40 (80% yield), and hexadecyl trifluoromethyl ether CF3O(CH2)15Me (95% yield). The cited papers also review earlier methods for the preparation of trifluoromethyl ethers 8 <2000BCJ471, 2001JOC1061, 2001MI815>. With 14CS2, correspondingly labeled RO14CF3 can be obtained <2001MI815>. Fluorination of a methoxy to a trifluoromethoxy group takes place in the synthesis of the ester CF3CF2CF2OCF(CF3)C(¼O)OCF2CF(OCF3)CClFCClF2 from the acid fluoride CF3CF2CF2OCF(CF3)C(¼O)F, the ester CF3CF2CF2OCF(CF3)C(¼O)OCH2CH(OMe)CHClCH2Cl, and F2 <2002WOP2002026688>.

ROH

ii. CS2 iii. MeI

1

RO

RO

X+

RO

SMe 6

SMe 3

X2S F

X+

RO

SMe

F–

SMe

–SX2

5

4

F F

S

RO

SMe 2

XS F

F–

X

S

i. NaH

X+

F F RO

X

S Me

F– –MeSX

ROCF3 8

7

Scheme 1

Chlorodifluoromethyl ethers (CClF2)OR are converted into trifluoromethyl ethers CF3OR in excellent yield and purity by treatment with BrF3 <2000JFC(102)363>. Aryl chlorodifluoromethyl ethers (CClF2)OAr are available both by condensation of the corresponding sodium phenoxide with CCl2F2 and by halogen exchange between the corresponding trichloromethyl ether CCl3OAr and liquid HF <2000JFC(103)81, 2001MI191>.

250

Functions Containing Four Halogens or Three Halogens

The selectivity of the photochlorination of aryl methyl ethers ArOMe with Cl2 to aryl trichloromethyl ethers CCl3OAr is improved by the removal of traces of the phenol ArOH in the starting material <2000WOP2000012456>. Photochlorination of the chiral methyl 1,2,2,2-tetrafluoroethyl ethers CF3CHFOMe yields the corresponding chiral trichloromethyl ethers CCl3OCHFCF3 <1995JOC1319>. Reaction of 2,2,3-trifluoro-2-(trifluoromethyl)oxirane with C(¼O)F2 leads to 2,3,3,3-tetrafluoro-3-(trifluoromethoxy)propanoyl fluoride CF3CF(OCF3)C(¼O)F, which, after hydrolysis and decarboxylation, gives trifluoroethenyl trifluoromethyl ether CF3OCF¼CF2 <1997JOC6160>. Upon treatment with C(¼O)F2 and KF (the synthetic equivalent of potassium trifluoromethoxide CF3OK) 2,2,2-trifluoroethyl trifluoromethanesulfonate CF3S(¼O)2OCH2CF3 yields 56% 2,2,2-trifluoroethyl trifluoromethyl ether CF3OCH2CF3 <1995JAP07179385>; cf. <1995JAP07179386>. Dichlorofluoromethyl ethers (CCl2F)OR have been prepared by treatment of trichloromethyl ethers CCl3OR with SbF3 and Br2 <1995JOC1319>. Upon treatment with catalytic SbCl5 and an equimolar amount of dichloroacetyl fluoride CHCl2C(¼O)F as the fluoride donor, trichloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether CCl3OCH(CF3)2 is converted into the corresponding dichlorofluoromethyl ether (CCl2F)OCH(CF3)2 <1999JFC(94)1>. A similar procedure with fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (commercially available as sevofluran) as the fluoride donor allows the conversion of trichloromethyl ethers CCl3OR to dichlorofluoromethyl ethers (CCl2F)OR and to chlorodifluoromethyl ethers (CClF2)OR, of dichlorofluoromethyl ethers (CCl2F)OR to chlorodifluoromethyl ethers (CClF2)OR, and of chlorodifluoromethyl ethers (CClF2)OR to trifluoromethyl ethers CF3OR <1998JFC(88)51>. Chlorodifluoromethyl 1,2,2-trichloro-1,2-difluoroethyl ether (CClF2)OCClFCCl2F, among other products, has been obtained by photochlorination of 2-chloro-1,2-difluoroethyl difluoromethyl ether CHClFCHFO(CHF2) (mixture of diastereomers). Minor products of the same reaction were difluoromethyl 1,1,2,2-tetrachloro-2-fluoroethyl ether (CHF2)OCCl2CCl2F, dichlorofluoromethyl 2,2,2-trichloro-1,1-difluoroethyl ether (CCl2F)OCF2CCl3, and 1,2,2-trichloro-1,2-difluoroethyl trichloromethyl ether CCl3OCClFCCl2F <1997JFC(82)9>. Aryl bromodifluoromethyl ethers (CBrF2)OAr have been obtained from sodium arenoxides ArONa and CBr2F2 <2001MI191>. A series of aryl difluoroiodomethyl ethers (CF2I)OAr have been prepared in modest yields by treatment of CF2I2 with alkyl-, methoxy-, or halo-substituted phenoxides <2000JFC(102)105>.

(iii) Trihalomethyl esters Trichloromethyl chloroformate CCl3OC(¼O)Cl (the commercially available ‘‘diphosgene’’) has been made by exhaustive photochlorination of methyl formate HC(¼ O)OMe or methyl chloroformate ClC(¼O)OMe <1998CNP1172102>. A manufacturing concept for bis(trichloromethyl)carbonate CCl3O(C¼O)OCCl3 9 (the commercially available ‘‘triphosgene’’) converts 9 and methanol to dimethylcarbonate MeOC(¼O)OMe which is then photochlorinated to 9 of >99% purity. This reaction generates 3 mol. 9 per mol. 9 originally consumed <2002CNP1336361>. Another patent describes the photochlorination of dimethylcarbonate to 9 in 99% yield <1998JAP10007623>. The ester peroxides CF3OC(¼O)OOC(¼O)OCF3 and CF3OC(¼O)OOOC(¼O)OCF3 are formed by photolysis of a mixture of TFAA, CO, and O2. Thermal decomposition of CF3OC(¼O)OOOC(¼O)OCF3 also furnishes, inter alia, CF3OC(¼O)OOC(¼O)OCF3 <2000IC1195, 2002MI1>. Trifluoromethylnitrite CF3ONO (presumably formed in the reaction of trifluoromethoxy radicals with NO) decomposes at room temperature to C(¼O)F2 and FNO. The somewhat labile trifluoromethylnitrate CF3ONO2 has been prepared in 15% yield in a pressure reaction between CF3OF and NO2. It is also formed by rearrangement of the unstable trifluoromethyl peroxynitrite CF3OONO <2001ZAAC(627)655>.

(iv) Trihalomethyl hypohalites, CHal13OHal2 Three patents disclose new approaches to the synthesis of the commercially available trifluoromethyl hypofluorite CF3OF. It can be obtained from C(¼O)F2 and F2 in the presence of metal fluorides such as KF and CsF <2003JAP2003081919> and from CO2 and F2 in the presence of CsF <2002JAP2002003451>.

Functions Containing Four Halogens or Three Halogens

251

Dichlorofluoromethyl hypofluorite (CCl2F)OF and chlorodifluoromethyl hypofluorite (CClF2)OF have been prepared from bis(1-chloro-2,2-difluoroethenyl) ether (CF2¼CCl)2O and OF2. Chlorodifluoromethyl hypofluorite is also formed in the photolysis of a mixture of OF2 and 1,3-dichloro-1,1,3,3-tetrafluoropropan-2-one <1968ZOB1410>. Trifluoromethyl hypochlorite CF3OCl, decomposing rapidly above 78 C, is formed by interaction of C(¼O)F2 with ClF in the presence of CsF <1986IS58>. Trifluoromethyl hypobromite CF3OBr, only observable at low pressure and temperature, has been obtained from CF3OCl and Bu4NBr3 in unspecified yield <1997IC2147>. Trifluoromethyl hypoiodite CF3OI has been observed as a product of the photochemical decomposition of the complex between CF3I and O3 <1985IC4234>. The hypothetical trichloromethyl hypochlorite CCl3OCl has been the subject of quantum chemical calculations <2000JPC(A)9581>. The fluorosulfenate CF3OSF has been prepared by UV irradiation of the isomeric sulfinyl fluoride CF3S(¼O)F <1988IC2706>.

(v) O-Trihalomethyl peroxides, CHal3OOR Bis(trifluoromethyl) peroxide CF3OOCF3 is commercially available. Difluorodioxirane CF2O2 reacts with C(¼O)F2 and CsF to form trifluoromethyl fluoroperformate FC(¼O)OOCF3 as well as oligomers of the type CF3O(OCF2O)nOC(¼O)F. The detailed reaction mechanism has been elucidated by 13C labeling <1999CC1671>. Trifluoromethyl peroxynitrite CF3OONO is a possible transient product of the photoreaction between CF3NO and O2 in an argon matrix <1987JPC3650>. Trifluoromethyl peroxynitrate CF3OONO2 (b.p. 0.9 C) has been obtained in 30–70% yield by photolysis of a mixture of CF3I, NO2, and O2 and removal of by-products by subsequent treatment with O3 <1998IC6208>; cf. <2001ZAAC(627)655>. Bis(trifluoromethyl) trioxide CF3OOOCF3 (m.p. 138 C) is most conveniently prepared in up to 87% yield by a pressure reaction of CsF, C(¼O)F2, and OF2 cf. <2001ZAAC(627)655>. The possible chemistry of the hypothetical bis(trifluoromethyl) tetroxide CF3OOOOCF3 has been considered theoretically <1997JCS(F)379>. The peroxide CF3OOC(¼O)OCF3 is one of the products of the photolysis of a mixture of [CF3C(¼O)]2O, CO2, and O2 <2000IC1195>.

(vi) Trihalomethyl sulfonates, CHal3OS(¼O)2R Trichloromethyl trifluoromethanesulfonate CF3S(¼O)2OCCl3 has been prepared in 90% yield from the mixed anhydride [CF3S(¼O)2O]3B and CFCl3 <1995JFC(73)17>.

(vii) N-Trihalomethoxy compounds, CHal3ON(¼O)nR No further advances have occurred in this area since the publication of chapter 6.07.2.1.1 in <1995COFGT(6)211>.

(viii) Metal trihalomethoxides, CHal3OM No further advances have occurred in this area since the publication of chapter 6.07.2.1.1 in <1995COFGT(6)211>.

6.07.2.1.2

Three halogens and a sulfur function

(i) Trihalomethanethiols, CHal3SH Trifluoromethanethiol CF3SH is formed upon irradiation of trifluoromethanethioic acid CF3C(¼O)SH in an inert gas matrix <1997JST(407)171>. The reactivity of the hypothetical trichloromethanethiol CCl3SH has been investigated in depth by quantum chemical methods <2002JPC(A)11581>.

252

Functions Containing Four Halogens or Three Halogens

(ii) Trihalomethyl sulfides, CHal3SR 2-Biphenylyl trifluoromethyl sulfide CF3SC6H4Ph-2 has been prepared from the corresponding methyl sulfide MeSC6H4Ph-2 by the standard sequence of photochlorination (to give CCl3SC6H4Ph-2) (in 82% yield) and subsequent halogen exchange with HF (86% yield) <1999JAP11049742>. The syntheses of a large number of geminal bis[(trifluoromethyl)sulfanyl] compounds derived from the ketene 2,2-bis[(trifluoromethyl)sulfanyl]ethenone (CF3S)2C¼C¼O have been described <1998JFC(89)9>. Sodium hydroxymethanesulfinate (rongalite) HOCH2SO2Na is a useful auxiliary in the preparation of alkyl trifluoromethyl sulfides CF3SAlk from aliphatic thiols AlkSH and CBrF3 in that it suppresses the competing formation of disulfides AlkSSAlk <2000JFC(105)41>. Trifluoromethyl sulfides CF3SAr and CF3SR have been prepared in a pressure reaction of CF3CO2K with diaryl disulfides ArSSAr and thiocyanates RSCN, respectively <2001JFC(107)311, 2002USP2002042542>. Aryl trifluoromethyl sulfides CF3SAr such as 2-chloro-5-nitrophenyl trifluoromethyl sulfide are available by heating of the corresponding diaryl disulfides ArSSAr with CF3CO2K in boiling tetrahydrothiophene 1,1-dioxide (sulfolane) <1999EP962450>. A 70% yield of 2-thiazolyl trifluoromethyl sulfide was obtained when 2-(trimethylsilyl)thiazole was treated with CF3SCl. The alternative reaction between 2-bromothiazole and CF3SCu was unsatisfactory <2002PS(177)2465>. Activated aromatic ring positions such as an unsubstituted 4-position of a pyrazole can be trifluoromethylsulfenylated to the corresponding sulfide CF3SAr with S-(trifluoromethyl) trifluoromethanethiosulfonate CF3S(¼O)2SCF3 <2002JAP2002338547>. O-(Trimethylsilyl)2,2,2-trifluoroethanal hemiaminals CF3CH(OSiMe3)NR2, together with tetrabutylammonium difluorotriphenylsilicate (De Shong’s reagent) [Bu4N][Ph3SiF2], convert disulfides RSSR to the corresponding trifluoromethyl sulfides CF3SR in good yields <2001TL2473>. A modest yield of benzhydryl and 4,40 -disubstituted benzhydryl trifluoromethyl sulfides CF3SCHAr2 is obtained in the reaction between thiobenzophenone and 4,40 -disubstituted thiobenzophenones, respectively, and commercial trimethyl(trifluoromethyl)silane CF3SiMe3 (Ruppert’s compound) in the presence of TBAF <2002HCA1644>. Trimethyl(trifluoromethyl)silane CF3SiMe3 neatly reacts with thiocyanates RSCN (with TBAF catalysis) <1997TL65> and arenesulfenyl chlorides ArSCl (with TASF, i.e., tris(dimethylamino)sulfonium difluorotrimethylsilicate, catalysis) <1995JFC(70)255> to form the corresponding trifluoromethyl sulfides CF3SR (30–87% yield) and aryl trifluoromethyl sulfides CF3SAr (59–72% yield), respectively. The photolysis of mixtures of disulfides RSSR and the corresponding trifluorothioacetate CF3C(¼O)SR (available from TFAA and the corresponding thiol RSH) or trifluoromethanethiosulfonate CF3S(¼O)2SR (available from CF3SO2Na, RSSR, and Br2), dissolved in MeCN, constitutes a mild method for the generation of trifluoromethyl sulfides CF3SR. In this way a highly functionalized trifluoromethyl sulfide such as methyl N-(trifluoroacetyl)-S-(trifluoromethyl)-L-cysteinate could be obtained in 60% yield. The reaction fails with aromatic substrates (R = Ar) <1999JOC3813>. Aromatic diazonium tetrafluoroborates ArN2BF4 react with CF3SCu to give the corresponding aryl trifluoromethyl sulfides CF3SAr in high yields. The reaction fails when the aryl group is donor substituted <2000CC987>. Activation of CF3SAg, CF3SCu, or (SCF3)2Hg with inorganic iodides was found to promote the formation of aryl trifluoromethyl sulfides CF3SAr in their reactions with halonitroarenes. Quantitative yields can be achieved <2000JOC1456>. Especially active salts like CF3SM (M = K, Me4N) 10, cf. Scheme 2, can be employed in this reaction <1999JFC(95)171>. S Cl

MF Cl

MeCN

CF3 S

M + 2MCl

10

M = K, Me4N

Scheme 2

A number of derivatives (such as esters and acid halides) of 2,2-bis[(trifluoromethyl)sulfanyl]ethanoic acid (CF3S)2CHCO2H, of 2-bromo-2,2-bis[(trifluoromethyl)sulfanyl]ethanoic acid (CF3S)2CBrCO2H, and of 2,2,2-tris[(trifluoromethyl)sulfanyl]ethanoic acid (CF3S)3CCO2H have been prepared by standard methods <1996CB1383>.

253

Functions Containing Four Halogens or Three Halogens

Mixed trihalomethyl sulfides and related compounds such as CF3SSCF3, CF3SSSCF3, CF3SCH2I, CF3SCH2SCF3, (CCl2F)SCF3, (CBrClF)SCF3, and CF3SCH2CN have been obtained from copper(I) trifluoromethanethiolate CF3SCu and various halomethanes. Also, S-(trifluoromethyl) thiocarbonates and thio-ortho-carbonates are formed <1996JFC(76)7>. Trifluoromethanide anion, generated by treatment of CHF3 with t-BuOK at 30 C, can be sulfenylated to the corresponding aryl trifluoromethyl sulfides CF3SAr by treatment with ArSSAr, ArSCl, or PhS(¼O)2SAr in yields ranging from 60% to 90% <1998T13771, 2000JOC8848>. Tetracoordinate sulfur intermediates, formed in situ by addition of potassium t-butoxide to CF3S(¼O)OR or CF3S(¼O)NR2, decompose with formation of CF3, which in turn converts aliphatic and aromatic disulfides RSSR to the corresponding sulfides CF3SR in modest yields <2003SL233>. 1-(1-Pyrrolidino)cyclopentene and 1-(1-pyrrolidino)cyclohexene react with N-[(trifluoromethyl)sulfanyl]phthalimide to yield the corresponding -[(trifluoromethyl)sulfanyl]cycloalkanones <2000SC2847> ,-Bis[(trifluoromethyl)sulfanyl]enamines such as (CF3S)2C¼CHNEt2 are formed in a complicated reaction sequence starting from CF3SCl and certain tertiary ethylamines EtNR1R2 <1995JFC(70)45>. Trimethylsilyl enol ethers R2C¼C(R)OSiMe3 react with CF3SCl to yield the corresponding -[(trifluoromethyl)sulfanyl]alkanones CF3SCR2C(¼O)R <2002PS(177)1021>. Aryl dichlorofluoromethyl sulfides (CCl2F)SAr have been prepared in a pressure reaction from the corresponding disulfides ArSSAr, sodium hydroxymethanesulfinate HOCH2SO2Na, and CCl3F <2001JOC643>.

(iii) Trihalomethyl sulfoxides and trihalomethyl sulfones, CHal3S(¼O)nR Different stereoisomers of 3,4-dimethylhexa-1,5-diyne-3,4-diol 11 react with CCl3SCl to give, via the corresponding bissulfenates 12, the corresponding 1,2-dimethyl-3,4-bis[(trichloromethylsulfinyl)methylene]cyclobutenes 13 with full stereochemical control, cf. Scheme 3 <2000TL6923>. 9-Fluorenyl trichloromethyl sulfoxide CCl3S(¼O)R (R = 9-fluorenyl) has been obtained by baseinduced rearrangement of 9-fluorenyl trichloromethanesulfenate CCl3SOR (R = 9-fluorenyl). Prop-2-enyl trichloromethyl sulfoxide CCl3S(¼O)CH2CH¼CH2 and 2-methylprop-2-enyl trichloromethyl sulfoxide CCl3S(¼O)CH2C(Me)¼CH2 can be rearranged to (E )-prop-1-enyl trichloromethyl sulfoxide (E)-CCl3S(¼O)CH¼CHMe and 2-methylprop-1-enyl trichloromethyl sulfoxide CCl3S(¼O)CH¼CMe2, respectively <1997T13933>. The phosphonate (MeO)2P(¼O)CH¼C¼CMe2 can be converted into the sulfoxide (MeO)2P(¼O)C(¼C¼CMe2)S(¼O)CCl3 by treatment with LDA and CCl3S(¼O)Cl <2000PS(166)265>.

Me R C C C OH HO C C C R Me

CCl3SCl –HCl

Me S CCl3 R C C C O O C C C R Me CCl3 S

11

12

O CCl3 S Me C R C R CCl3 S O 13

Me

Scheme 3

While the oxidation of 1,2-bis[(trifluoromethyl)sulfanyl]benzene 1,2-(CF3S)2C6H4 to the corresponding bissulfoxide 1,2-[CF3S(¼O)]2C6H4 is readily achieved with MCPBA the corresponding oxidation of the 1,4-isomer apparently requires a different oxidant, i.e., SELECTFLUOR, [1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)], a source of electrophilic fluorine <2001USP6215021>. The insecticidal GABA-gated chloride channel blocker fipronil, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile 14 is an important commercial trifluoromethyl sulfoxide. Its industrial preparation by oxidation of the corresponding sulfide with trifluoroperacetic acid CF3CO3H has been fine tuned <2001WOP0130760>.

254

Functions Containing Four Halogens or Three Halogens

5-Amino-3-methyl-1-phenylpyrazole can be trifluoromethylsulfinylated in the 4-position by treatment with N-[(trifluoromethyl)sulfinyl]succinimide which in turn is obtained from N-lithiosuccinimide and CF3S(¼O)Cl <2003EUP1331222>.

CF3 NC N

S O N

Cl

NH2 Cl

CF3 14

Protonated trifluoromethanesulfinic acid [CF3SO2H2]+ appears to be the reactive species in the CF3SO2Na(K)CF3SO3H mixture which converts arenes ArH with o,p-directing substituents to the corresponding sulfoxides CF3S(¼O)Ar with predominant p-substitution. Yields range from 55% to 82%. In the absence of activating substituents in the substrate, i.e., with benzene, only 24% yield can be achieved. With CF3OPh as ArH only one product, 1,4(CF3O)C6H4[S(¼O)CF3] is formed <2001SL550>. 1-Methylpyrrole could be trifluoromethylsulfinylated in the 2-position with an in situ reagent [equivalent to [CF3S(¼O)]+] prepared from CF3SO2Na and Cl3P(¼O) <1999T7243>. Trimethyl(trifluoromethyl)silane CF3SiMe3, in the presence of catalytic amounts of TBAF, neatly reacts with arenesulfinyl chlorides ArS(¼O)Cl to form the corresponding trifluoromethyl sulfoxides CF3S(¼O)Ar (53–61% yield) <1995JFC(70)255>. Tolyl trifluoromethyl sulfone CF3S(¼O)2C6H4Me-4 has been prepared in 83% yield from 4-MeC6H4S(¼O)2F, CF3SiMe3, and TASF <1995JFC(70)255>. Contrary to all other (mostly aromatic) sulfides tested, oxidation of phenyl trifluoromethyl sulfide CF3SPh with methyl(trifluoromethyl)dioxirane Me(CF3)CO2 is >99% selective towards the formation of the corresponding sulfoxide CF3S(¼O)Ph and no trace of the sulfone is formed <2002JA9154>. Bis(trifluoromethyl) sulfoxide CF3S(¼O)CF3 and phenyl trifluoromethyl sulfoxide CF3S(¼O)Ph have been prepared by reaction of dimethyl sulfite (MeO)2S(¼O) and methyl benzenesulfinate PhS(¼O)OMe, respectively, with CsF and CF3SiMe3 <1999JOC2873>. Dichlorofluoromethyl phenyl sulfone (CCl2F)S(¼O)2Ph is the major product (90% yield) of the oxidation of the sulfide (CCl2F)SPh with excess H2O2 in AcOH with the corresponding sulfoxide (CCl2F)S(¼O)Ph as the minor product (5% yield) <2001JOC643>. Methyl methanesulfonate MeS(¼O)2OMe and methyl benzenesulfonate PhS(¼O)2OMe, give methyl trifluoromethyl sulfone CF3S(¼O)2Me and phenyl trifluoromethyl sulfone CF3S(¼O)2Ph, respectively, when treated with CsF and CF3SiMe3 <1999JOC2873>. The extremely volatile sulfone [CF3S(¼O)2]3CF has been made from the corresponding lithium salt [CF3S(¼O)2]3CLi and F2. Contrary to expectation, it does not constitute a source of F+ <2003JFC(122)233>.

(iv) S-Trihalomethyl thio- and dithioesters, CHal3SC(¼Z)R (Z = O or S) An S-(trifluoromethyl) androstane-17-carbothioate RC(¼O)SCF3 has been prepared by trifluoromethylation of the corresponding carbothioic acid RC(¼O)SH with CBrF3 or CClF3 <1998ILP109656>. The S-thioester (CF3S)2CHC(¼O)SCF3 has been obtained by addition of CF3SH to the ketene (CF3S)2C¼C¼O <1998JFC(89)9>.

(v) Trihalomethanesulfenyl, -sulfinyl, and -sulfonyl halides, CHal13S(¼O)nHal2 The known compounds are listed in Tables 1–3.

Functions Containing Four Halogens or Three Halogens

255

Table 1 Trihalomethanesulfenyl halides CHal3SHal CAS RN

CHal3

References

Trihalomethanesulfenyl fluorides CHal3SF [17742-04-0] [17742-03-9] [17742-02-8] [2712-94-9]

CF3 CClF2 CCl2F CCl3

<1993JST(301)65> <1993JST(301)65> <1993JST(301)65> <1981MI399>

Trihalomethanesulfenyl chlorides CHal3SCl CF3 CClF2 CCl2F CCl3 CCl3 (35S labeled)

[421-17-0] [993-38-4] [2712-93-8] [594-42-3] [244082-02-8]

commercially available <1964AG807> <1993JST(301)65> commercially available <1999MI225>

Trihalomethanesulfenyl bromides CHal3SBr [753-92-4] [993-37-3] [993-36-2] [993-35-1] [993-34-0] [993-32-8] [993-33-9] [993–31-7] [753-91-3] [993-30-6]

CF3 CClF2 CCl2F CCl3 CBrF2 CBr2F CBrCl2 CBr2Cl CBrClF CBr3

<1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807> <1964AG807>

Trihalomethanesulfenyl iodides CHal3SI CF3

[102127-62-8]

<1992ZAAC(611)114>

Table 2 Trihalomethanesulfinyl halides CHal3S(¼O)Hal CAS RN

CHal3

References

Trihalomethanesulfinyl fluorides CHal3S(¼O)F CF3 CF3 (13C labeled) CF3 (18O labeled) CClF2

[812-12-4] [115095-68-6] [115095-69-7] [63177-65-1]

<1968JA5403> <1968JA5403> <1968JA5403> <1977JFC(9)233>

Trihalomethanesulfinyl chlorides CHal3S(¼O)Cl CF3 CCl2F CCl3

[20621-29-9] [156904-01-7] [25004-95-9]

<2001USP6316636> <1992IC492> commercially available

Trihalomethanesulfinyl bromides CHal3S(¼O)Br CF3 CCl3

[20621-30-1] [503844-33-5]

<1988ZAAC(537)169> <1968ACS3256>

Trihalomethanesulfinyl iodides CHal3S(¼O)I CF3

[108863-76-9]

<1988ZAAC(537)169>

Trifluoromethanesulfinyl chloride CF3S(¼O)Cl can be prepared in situ from the commercially available trifluoromethanesulfonyl chloride CF3S(¼O)2Cl and trimethyl phosphite (MeO)3P <2001TL1391>. An improved synthesis of trifluoromethanesulfonyl fluoride CF3S(¼O)2F, useful in lithium battery technology, has been achieved by fluorination of MeS(¼O)2F with F2 in perfluoro-2-methylpentane <2003JFC(120)105>. A low yield (18%) synthesis of

256

Functions Containing Four Halogens or Three Halogens Table 3 Trihalomethanesulfonyl halides CHal3S(¼O)2Hal CAS RN

CHal3

References

Trihalomethanesulfonyl fluorides CHal3S(¼O)2F CF3 CClF2 CBrF2 CF2I CCl3

[335-05-7] [64544-26-9] [73043-96-6] [73043-97-7] [1495-34-7]

<1994IC3281> <1979S972> <1979S972> <1979S972> <1970MI795>

Trihalomethanesulfonyl chlorides CHal3S(¼O)2Cl CF3 CClF2 CCl2F CCl3 CCl3 (35S labeled) CBrF2

[421-83-0] [1495-29-0] [1495-33-6] [2547-61-7] [244082-03-9] [146691-88-5]

commercially available <1993IC5007> <1993IC5007> commercially available <1999MI225> <1992MI274>

Trihalomethanesulfonyl bromides CHal3S(¼O)2Br CF3 CBrF2 CCl3

[15458-53-4] [146691-81-8] [993-51-1]

<2001WOP0127076> <1992MI274> <1997JCR(S)6>

(CClF2)S(¼O)2Cl has been achieved by reaction of zinc hydroxymethanesulfinate (HOCH2 SO2)2Zn with CBrClF2 and subsequent chlorination of the intermediate (CClF2)SO2H salt with Cl2 <1989JOC2452>.

(vi) Trihalomethanesulfenic, -sulfinic, and -sulfonic derivatives, CHal3S(¼O)nZR Benzyl trifluoromethansulfenate CF3SOCH2Ph has been prepared in a one-pot reaction by oxidation of benzyl trifluoromethyl sulfide CF3SCH2Ph with H2O2 <2001USP6316636>. Trifluoromethanesulfinates CF3S(¼O)OR and trifluoromethanesulfinamides CF3S(¼O)NR1R2 are available by reaction of the corresponding precursors ROH and R1R2NH, respectively, with an in situ reagent (equivalent to [CF3S(¼O)]+) prepared from CF3SO2Na and Cl3P(¼O) <1999T7243>. 9-Fluorenyl trichloromethanesulfenate CCl3SOR (R = 9-fluorenyl) has been prepared in 86% yield by the standard method <1997T13933>. Potassium trifluoromethanesulfinate CF3SO2K, an important synthetic intermediate, is available from a pressure reaction between CF3CO2K and SO2 <2002USP2002042542>. Propargylic alcohols HCCCR1R2OH react with trifluoromethanesulfinyl chloride CF3S(¼O)Cl to give the corresponding sulfinates CF3S(¼O)OCR1R2CCH which in turn can be further converted by rearrangement into the corresponding allenyl sulfones CF3S(¼O)2CH¼C¼CR1R2 <2001TL1391>. In situ generation of trifluoromethanesulfinyl chloride CF3S(¼O)Cl from CF3S(¼O)2Cl and (MeO)3P allows the convenient conversion of the appropriate amines RNH2 to the trifluoromethanesulfinamides CF3S(¼O)NHR <1998SUL63>. Sodium trifluoromethanesulfinate CF3SO3Na, useful as intermediate in the synthesis of CF3S(¼O)Cl, has been obtained by the treatment of 2-chlorocyclohexyl trifluoromethyl sulfone with NaOH <2001USP6316636>. Trifluoromethanesulfinamides CF3S(¼O)NHR are also formed by the interaction of N-sulfinylamines R-N¼S¼O with CF3SiMe3 and Me4NF (75–85% yield) <2002TL3029>. Treatment of trifluoromethoxy substituted aliphatic ethers with a mixture of commercially available trifluoromethanesulfonic anhydride Tf2O and CF3SO3H leads to trifluoromethoxy substituted trifluoromethanesulfonic esters such as CF3S(¼O)2O(CH2)2OCF3 useful as alkylating agents <2001JOC1061>. Trifluoromethanethiosulfonic acid S-esters CF3S(¼O)2SR, including CF3S(¼O)2SCCl3, have been prepared from CF3SO2Na and the appropriate sulfenyl chlorides RSCl (or bromides RSBr). Trifluoromethaneselenosulfonic acid Se-esters CF3S(¼O)2SeR are accessible with the corresponding selenyl chlorides RSeCl (or bromides RSeBr) as starting materials. Yields range from 50% to 95% <1996JOC7545>.

Functions Containing Four Halogens or Three Halogens

257

N-[(Trifluoromethyl)sulfinyl]trifluoromethanesulfonamide CF3S(¼O)2NHS(¼O)CF3 has been prepared in a lengthy procedure starting from bis(trifluoromethyl) disulfide CF3SSCF3, N,N-dichlorotrifluoromethanesulfonamide CF3S(¼O)2NCl2, and trifluoromethanesulfinyl chloride CF3S(¼O)Cl <2002JFC(115)129>. The chemistry and the materials science aspects of the commercially available trifluoromethanesulfonimide [CF3S(¼O)2]2NH have been reviewed <2002JCS(P1)1887>. S,S-Dimethyl-N-[(trifluoromethyl)sulfonyl]iminodithiocarbonate CF3S(¼O)2N¼C(SMe)2, a useful intermediate for the preparation of N-[(trifluoromethyl)sulfonyl]ureas and -guanidines, has been obtained in 85% yield by treatment of S,S-dimethyl iminodithiocarbonate HN¼C(SMe)2 with Tf2O <2003JFC(124)151>. N-Sulfinyltrichloromethanesulfonamide CCl3SO2N¼S¼O has been prepared by treatment of the corresponding sulfonamide with SOCl2 <1982LA545>. The compound CCl3S(¼O)N[S(¼O)2Me]2 has been prepared by trichloromethanesulfinylation of silver(I) trifluoromethanesulfonimidate [MeS(O)2]2NAg with CCl3S(¼O)Cl <1998ZN(B)734>.

(vii) Metal trihalomethanethiolates, CHal3SM Particularly nucleophilic salts of trifluoromethanethiol 10 can be obtained by reaction in MeCN of thiophosgene C(¼S)Cl2 with anhydrous KF or Me4NF, cf. Scheme 2 <1999JFC(95)171>. The preparation of the trifluoromethanethiolates of copper(I), CF3SCu (commercially available), silver(I), CF3SAg, and mercury(II), (CF3S)2Hg (commercially available) and their use for the introduction of CF3S groups into organic compounds have been reviewed <1996JFC(76)7>. The important synthetic intermediate CF3SCu has been prepared in 98% yield from CS2, AgF, and CuBr <2001USP6215021>. Bis(trifluoromethyl) disulfide CF3SSCF3 reacts with tetrakis(dimethylamino)ethene (Me2N)2C¼C(NMe2)2 to form the salt (Me2N)2C+– C+(NMe2)22CF3S the anion of which can be alkylated or arylated to give trifluoromethyl sulfides such as CF3SCH2Ph, CF3SC5NF4, and CF3SC6H3(NO2)2-2,4 in 80–95% isolated yield <2000JCS(P1)2183>.

6.07.2.1.3

Three halogens and an Se or Te function

(i) (Trihalomethyl) selenium compounds, CHal3SeR Tetramethylammonium trifluoromethaneselenolate [Me4N][CF3Se], a useful synthetic intermediate, is available in 65% yield from red selenium, CF3SiMe3, and Me4NF <2003JFC(123)183>. The syntheses of a large number of geminal bis[(trifluoromethyl)selanyl] compounds derived from the ketene 2,2-bis[(trifluoromethyl)selanyl]ethenone (CF3Se)2C¼C¼O have been described <1998JFC(89)9>. O-(Trimethylsilyl)-2,2,2-trifluoroethanal hemiaminals CF3CH(OSiMe3)NR2, together with tetrabutylammonium difluorotriphenylsilicate [Bu4N][Ph3SiF2], convert aromatic diselenides ArSeSeAr to the corresponding trifluoromethyl selenides CF3SeR in good yields <2001TL2473>. Trifluoromethanide anions, generated from CHF3 in different ways, react with diphenyl diselenide PhSeSePh to give phenyl trifluoromethyl selenide CF3SePh in fair yield <2000JOC8848>. Trimethyl(trifluoromethyl)silane CF3SiMe3, in the presence of catalytic amounts of TBAF, neatly trifluoromethylates selenocyanates RSeCN to the corresponding trifluoromethyl selenides CF3SeR (58–75% yield) <1997TL65>. A large number of new trifluoromethylselanyl compounds such as (CF3Se)3CF, (CF3Se)3CCl, (CF3Se)3CBr, (CF3Se)3CC(SeCF3)3, and (CF3Se)2C¼C(SeCF3)2 have been obtained from tris[(trifluoromethyl)selanyl]methylium hexafluoroarsenate [(CF3Se)3C][AsF6] as the common precursor <1996CB1383>. N-[(Trifluoromethyl)selanyl]succinimide has been prepared from trifluoromethaneselenyl chloride CF3SeCl and silver(I) succinimidate <1996CB1383>. A particularly mild method for the preparation of phenyl trifluoromethyl selenide CF3SePh in 58% yield consists of the photolysis of Se-phenyl trifluoromethanselenosulfonate CF3S(¼O)2SePh (prepared from CF3SO2Na, PhSeSePh, and Br2) in the presence of equimolar PhSeSePh <1999JOC3813>. Bis(trifluoromethyl) selenoxide CF3Se(¼O)CF3 has been prepared in 84% yield from dimethyl selenite (MeO)2Se(¼O), CsF, and CF3SiMe3 <1999JOC2873>. The same selenoxide CF3Se(¼O)CF3 has also been prepared from bis(trifluoromethyl) selenide CF3SeCF3 and hypofluorous acid HOF <2000JFC(102)301>.

258

Functions Containing Four Halogens or Three Halogens

(ii) (Trihalomethyl)tellurium compounds, CHal3TeR The chemistry of (trifluoromethyl)tellurium compounds has been reviewed. The key compounds described as useful intermediates are CF3TeCF3, CF3TeTeCF3, CF3TeI, and (CF3Te)2Hg <2001PS(171-172)113>. Aromatic Te-(trifluoromethyl) tellurocarboxylates ArC(¼O)TeCF3 are available by reaction of the corresponding acyl chlorides ArC(¼O)Cl with trifluoromethyl trimethylstannyl telluride CF3TeSnMe3. This same tellurium reagent replaces two of the three chlorine atoms of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) with (trifluoromethyl)telluranyl groups. The reaction between CBr4 and CF3TeSnMe3 is assumed to give tetrakis(trifluoromethyl)tellurium (CF3)4Te which decomposes spontaneously to bis(trifluoromethyl) ditelluride CF3TeTeCF3 and tetrakis[(trifluoromethyl)telluranyl]ethene (CF3Te)2C¼C(TeCF3)2 <1999JFC(94)195>. Bis(trifluoromethyl)tellurium dichloride (CF3)2TeCl2 reacts with AgNSO to yield the labile tellurium compound (CF3)2Te(NSO)2 <2000JFC(102)301>.

6.07.2.2 6.07.2.2.1

Three Halogens and a Group 15 Element Three halogens and a nitrogen function

(i) Trihalomethylamines, CHal3NR2 (a) Primary trihalomethylamines. No further advances have occurred in this area since the publication of chapter 6.07.2.2.1 in <1995COFGT(6)211>. (b) Secondary trihalomethylamines. The serendipitous formation of a secondary trifluoromethylamine was observed when the attempted simple halogen exchange of 2-(trichloromethyl)phenyl isocyanate 15 with HF yielded 2-[(trifluoromethyl)amino]benzoyl fluoride 16 rather than the expected 2-(trifluoromethyl)phenyl isocyanate 17 <1982JFC(19)553>. O C N

CF3 NH

HF

C F

CCl3 15

O

16 HF

O C N CF3 17

(c) Tertiary trihalomethylamines. Electrochemical fluorination of methyl 2-methyl-3-(dimethylamino)propanoate leads to 2% of the perfluorinated product (CF3)2NCF2CF(CF3)C(¼O)OCF3, together with, inter alia, 36% (CF3)2NCF2CF(CF3)C(¼O)F and 5% (CF3)2NC3F7. Similar results were seen in the electrofluorination of methyl 3-(dimethylamino)butanoate <1994JFC(66)193>. Solution-phase fluorination with F2 of TMEDA in the presence of NaF gives a 20% yield of the perfluorinated product (CF3)2NCF2CF2N(CF3)2 <2003JFC(123)233>. Secondary amines R1R2NH can be converted into the corresponding tertiary trifluoromethylamines CF3NR1R2 by treatment with BuLi, CS2, and MeI, and subsequent fluorination of the resulting methyl dithiocarbamate with [Bu4N][H2F3] and 1,3-dibromo-5,5-dimethylhydantoin. Labeled compounds 14CF3NR1R2 are obtained with 14CS2 <2001MI815>. A large number of tertiary trifluoromethylamines such as perfluoro-1,4-dimethylpiperazine CF3N(CF2CF2)2NCF3

Functions Containing Four Halogens or Three Halogens

259

have been obtained by electrofluorination of 1-[2-(methoxycarbonyl)ethyl]-4-methylpiperazine MeN(CH2CH2)2NCH2CH2C(¼O)OMe and related compounds <2001JFC(108)21>. Hexakis(trifluoromethyl)tetrazane (CF3)2NN(CF3)N(CF3)N(CF3)2 is formed in 90% yield upon photolysis of N-chloro-N,N0 ,N0 -tris(trifluoromethyl)hydrazine (CF3)2NN(Cl)CF3 <1995AG(E)586>.

(ii) N-(Trihalomethyl)amides, CHal3NRC(¼O)R The imines CF3N¼CF(CF3) and CF3N¼CF(C2F5) react with AcOH with loss of acetyl fluoride to yield the N-(trifluoromethyl)amides (CF3)NHC(¼O)CF3 and (CF3)NHC(¼O)C2F5, respectively <1988IZV833>.

(iii) Trihalomethyl isocyanates, CHal3N¼C¼O; trihalomethyl isocyanide dihalides, CHal3N¼CHal2 and N-(trihalomethyl)carbodiimides, CHal3N¼C¼NR All known trihalomethyl isocyanates CHal3N¼C¼O (Hal¼F, Cl, Br) have been shown to exist in equilibrium with their halotropic isomers, the halocarbonyl isocyanide dihalides CHal2¼NC(¼O)Hal with the latter strongly predominating <1996ZOB1715>. (a) Trifluoromethyl isocyanate. No further advances have occurred in this area since the publication of chapter 6.07.2.2.1 in <1995COFGT(6)211>. (b) Trichloromethyl isocyanate. This compound is listed in the 2003–2004 Aldrich catalog. However, early as well as more recent work has shown that its equilibrium with chlorocarbonyl isocyanide dichloride Cl2C¼NC(¼O)Cl lies completely to the right <1996ZOB1715>. (c) Tribromomethyl isocyanate. No further advances have occurred in this area since the publication of chapter 6.07.2.2.1 in <1995COFGT(6)211>. (d) Triiodomethyl isocyanate. There is no record of this compound. (e) Fluorodichloromethyl isocyanate. The isomeric fluorocarbonyl isocyanide dichloride Cl2C¼NC(¼O)F is available from Cl2C¼NC(¼O)Cl and AgF <1968AG(E)630>. (f) Bromodifluoromethyl isocyanate. Photochemical insertion of CO into the NBr bond of CF2¼NBr gives a 55% yield of (CBrF2)N¼C¼O. No halotropic equilibrium with CF2¼NC(¼O)Br or other isomers has been reported <1988JOC4443>. (g) Trifluoromethyl isocyanide difluoride. Pyrolysis of alkali metal 2-[bis(trifluoromethyl)amino]-2,2-difluoroethanoates such as (CF3)2NCF2CO2Na gives, among other products, difluoro-N-(trifluoromethyl)methanimine CF3N¼CF2 <1999JFC(95)161>. The defluorination of CF3N¼CF2 with Ph3P proceeds smoothly to yield 80%–90% trifluoromethyl isocyanide CF3NC <1995IC3114>.

(iv) N-Halo(trihalomethyl)amines, CHal13NRHal2 N,N-Dichlorotrifluoromethylamine CF3NCl2 is available by addition of ClF to ClCN in the presence of catalytic CsF <1991IC2699>. Addition of ClF to the hydrazone (CF3)2NN¼CF2 produces N-chloro-N,N0 ,N0 -tris(trifluoromethyl)hydrazine (CF3)2NN(Cl)CF3 <1995AG(E)586>.

(v) N-(Trihalomethyl)hydroxylamines, CHal3NR1OR2; trihalonitrosomethanes CHal3NO, trihalonitromethanes, CHal3NO2, and related compounds N,N-Bis(trifluoromethyl)-O-fluorohydroxylamine (CF3)2NOF is available from difluoro-N(trifluoromethyl)methanimine CF3N¼CF2 and OF2 in the presence of CsF, but decomposes spontaneously to trifluoronitrosomethane CF3NO and CF4. If the same reagents are used in the ratio 2:1 the hydroxylamine derivative 1,1,3,3-tetrakis(trifluoromethyl)-2,1,3-oxadiazane (CF3)2NON(CF3)2 is formed in 77% yield <1999JFC(99)145>. In the presence of CsF trimethyl(trifluoromethyl)silane CF3SiMe3 reacts with NOCl to form trifluoronitrosomethane CF3NO in 92% yield and with excellent purity <2002CC1818>. Another possibility for the preparation of CF3NO is the reaction of (CF3)2Cd with NOCl (yield 98%) <1995JFC(73)273>. Trichloronitrosomethane CCl3NO can be prepared on a commercial scale by photonitrozation of CHCl3 with NOCl <2001JAP2001002625>.

260

Functions Containing Four Halogens or Three Halogens

Tribromonitrosomethane CBr3NO and the mixed trihalonitrosomethanes CClF2NO, CCl2FNO, CBrCl2NO, and CBr2ClNO are on record in the older literature (with the extremely hazardous mercury(II) fulminate as the most common ultimate synthetic precursor) <1980SA(A)75> as is CBrF2NO <1953JCS2075>. A substantially simplified synthesis of trifluoronitromethane CF3NO2 has been achieved in the shape of the photoreaction of CF3I with NO2 (35% yield; only highly volatile by-products are formed which can be readily removed by treatment with excess CsF). This method could also be used to prepare the labeled CF15 3 NO2 <2002JFC(117)181>. A yield of 47% CF3NO2 is achieved in the reaction of isopropyl nitrate Me2CHONO2 with (trifluoromethyl)zinc bromide CF3ZnBr and AlCl3 <1995JFC(73)273>. Trichloronitromethane (chloropicrin) CCl3NO2 is commercially available as a versatile C1 reagent. Tribromonitromethane (bromopicrin), along with bromonitromethane and dibromonitromethane, has been obtained by bromination of nitromethane with t-butyl hypobromite Me3COBr in the presence of hex-1-ene (yield 71%) <1976JOC1285>. Treatment of nitromethane with a Br2/Cl2 mixture in the presence of water and NaOH yields 33% CBrCl2NO2, 35% CBr2ClNO2, 13% CCl3NO2, and 18% CBr3NO2 <1964USP3159686>. Neither triiodonitrosomethane CI3NO nor triiodonitromethane CI3NO2 are known except for a theoretical treatment of CI3NO2 <1972JST321>. Chlorodifluoronitromethane CClF2NO2 has been prepared by oxidation of chlorodifluoronitrosomethane CClF2NO <1953JCS2075>. The compounds CClF2NO2 and CBrF2NO2, respectively, have been obtained by treatment of difluoronitroethanoic acid with XeF2 and Cl2 or Br2. Corresponding treatment of chlorofluoronitroethanoic acid with XeF2, Cl2 and Br2, respectively, gives CCl2FNO2 and CBrClFNO2 <1988IZV2639>. The compounds CCl2INO2 and CF2INO2 have been considered theoretically <1972JST321>.

(vi) N-(Trihalomethyl)sulfenamides, CHal3SNR1R2 Simple trifluoromethanesulfenamides CF3SNR1R2 have been prepared from CF3SCl and secondary aliphatic amines <1995JFC(70)45>. Several imide type heterocycles have been N-sulfenylated with CCl3SCl <2000PS(161)213>.

(vii) Metal (trihalomethyl)amides, CHal3NRM No further advances have occurred in this area since the publication of chapter 6.07.2.2.1 in <1995COFGT(6)211>.

(viii) Miscellaneous compounds Trifluoromethyl azoxy compounds have been reviewed. In the case of (Z)-1-fluoro-2-(trifluoromethyl)diazene 2-oxide (Z)-CF3N(¼O)¼NF, obtained from the reaction of trifluoronitrosomethane CF3NO with tetrafluorohydrazine N2F4, the structure could be confirmed by gas-phase electron diffraction although quantum chemical calculations showed the corresponding 1-oxide to be more stable by 12 kcal mol1. Apparently, the energy of activation for the corresponding isomerization is of considerable magnitude <2002IC6125>.

6.07.2.2.2

Three halogens and a phosphorus function

When triphenyl phosphite (PhO)3P is treated with excess CBrF3 and (Et2N)3P, an 85% yield of tris(trifluoromethyl)phosphine (CF3)3P is obtained <1996JFC(79)103>. Dichlorophosphines RPCl2 react with equivalent amounts of CBrF3 and tris(diethylamino)phosphine (Et2N)3P to give the corresponding bis(trifluoromethyl)phosphines (CF3)2PR 18, which upon further elaboration yield bis(trifluoromethyl)-substituted phosphoranes. The phosphines 18 can be methylated with methyl trifluoromethanesulfonate CF3S(¼O)2OMe to give the corresponding phosphonium sulfonates [(CF3)2P(R)Me][CF3SO3] <2002HAC650>. When bis(trifluoromethyl)phosphine (CF3)2PH is treated with tetraethylammonium cyanide Et4NCN, the bis(trifluoromethyl)phosphanide anion

Functions Containing Four Halogens or Three Halogens

261

[(CF3)2P] 19 is formed (with evolution of HCN). The phosphanide anion 19 is only stable below 30 C, but can be considerably stabilized as a CS2 adduct, [(CF3)2PCS2] <2002IC2260>. Alkylation of 19 with ethylene ditosylate 4-MeC6H4S(¼O)2OCH2CH2OS(¼O)2C6H4Me-4 leads to the bisphosphine (CF3)2PCH2CH2P(CF3)2 <2001IC3113>. Solution-phase perfluorination of 1,2-bis(dimethylphosphino)ethane Me2PCH2CH2PMe2 affords the bisphosphorane (CF3)2P(F2)CF2CF2P(F2)(CF3)2 <2000JFC(102)333>. A poor yield (15%) of 1,2-bis[bis(trifluoromethyl)phosphino)]ethane (CF3)2PCH2CH2P(CF3)2 has been obtained upon treatment of 1,2-bis(dichlorophosphino)ethane Cl2PCH2CH2PCl2 with CBrF3 and (Et2N)3P <1992TL7601>. Both the tetraphosphetane [(CF3)P]4 and the pentaphospholane [(CF3)P]5 decompose to bis(trifluoromethyl)diphosphene (CF3)P¼P(CF3) which can be trapped in cycloadditions with alka-1,3-dienes <1995ZN(B)189>. The bis(trichloromethyl)phosphine 2,4,6-Me3C6H4P(CCl3)2 can be prepared in good yield by reaction of the phosphorane 2,4,6-Me3C6H4P¼CCl2 with CCl4 and (Et2N)3P <1992ZOB948>.

6.07.2.2.3

Three halogens and an As, Sb, or Bi function

Trihalomethylarsines such as (CF3)3As, (CF3)2As(CClF2), and CF3As(CF2Cl)2 can be obtained from solvent-free (CF3)2Cd and AsCl3. Also the corresponding dihaloarsoranes R1R2R3AsHal1Hal2 are formed <1995JOM(503)C51>. Trifluoronitrosomethane CF3NO reacts with trifluoromethylarsine (CF3)AsH2 to form the hydroxylamine derivative (CF3)As[ONH(CF3)]2 and with bis(trifluoromethyl)arsine (CF3)2AsH to give the analogous (CF3)2AsONH(CF3). The latter reacts with bis(trifluoromethyl)nitroxyl radicals (CF3)2NO to give, inter alia, (CF3)2AsON(CF3)2 <1996JFC(79)111>. The metal complex (CF3)2AsMn(CO)5 can be made from tetrakis(trifluoromethyl)diarsane (CF3)2AsAs(CF3)2 and pentacarbonylmanganese(I) iodide Mn(CO)5I <2002ZAAC(628)2523>. The cycloarsanes [(CF3)As]4.5 decompose to bis(trifluoromethyl)diarsene (CF3)As¼As(CF3) which can be trapped in cycloadditions with alka-1,3-dienes <1995ZN(B)189>. Tris(trifluoromethyl)antimony (CF3)3Sb has been prepared in 61% yield from (CF3)PbPh3 and SbI3 <2000OM2603>. Ligand exchange of the bismuthane compounds ArBiBr2 and Ar2BiCl with (CF3)2Cd yields (CF3)2BiAr and (CF3)BiAr2, respectively. The former rapidly disproportionates to (CF3)BiAr2 and (CF3)3Bi <1994JFC(69)219>. Tris(trifluoromethyl)bismutane (CF3)3Bi and copper(II) acetate react with each other to form (CF3)2BiOAc and CF3Bi(OAc)2. This mixture can be used in trifluoromethylations, for instance of [Bu4N][SPh], where CF3SPh is formed in undetermined yield <2000JFC(106)217>.

6.07.2.3 6.07.2.3.1

Three Halogens and a Metalloid Three halogens and a silicon function

Trimethyl(trifluoromethyl)silane (CF3)SiMe3, trimethyl(trichloromethyl)silane (CCl3)SiMe3, and trichloro(trichloromethyl)silane (CCl3)SiCl3 are commercially available. The silanes (CClF2)SiMe3 and (CBrF2)SiMe3 are available by interaction of CBrClF2 and CBr2F2, respectively, with aluminum and Me3SiCl <1997JA1572>. Catalytic thermal decarboxylation of silyl trichloroacetates CCl3C(¼O)OSiMe2R gives the corresponding trichloromethylsilanes (CCl3)SiMe2R <1995IZV150>. Insertion of diaminosilylenes (R1R2N)2Si into a CCl bond of CCl4 gives the corresponding amino-substituted 1-chloro-2-(trichloromethyl)disilanes (R1R2N)2Si(CCl3)Si(Cl)(NR1R2)2 <2002JA4186>. A minuscule yield (3%) of 2,2-dibromo-1,1,3,3,5-pentamethyl-5-(tribromomethyl)-1,3,5-(trisilacyclohexane) 21 has been obtained by photobromination of 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane 20 <2000CJC1388>. Br Me2Si

SiMe2

SiMe2 20

Br2

Br SiMe2

Me2Si

hν Me

Si 21

CBr3

262 6.07.2.3.2

Functions Containing Four Halogens or Three Halogens Three halogens and a boron function

Potassium tetrakis(trifluoromethyl)borate K[B(CF3)4] is available via treatment of ammonium tetracyanoborate NH4[B(CN)4], dissolved in liquid HF, with ClF3 or ClF. The primary step in this conversion is assumed to be an addition to the CN triple bond, cf. Scheme 4 <2001CEJ4696>. As a rule of thumb trifluoromethyl derivatives of tricoordinate boron are unstable while those of tetracoordinate boron are much more accessible. Thus, while tris(trifluoromethyl)borane (CF3)3B still eludes its isolation and characterization, its impressively stable adduct with carbon monoxide (CF3)3BCO (m.p. 9 C) has been prepared by partial hydrolysis of the salt K[B(CF3)4]. When (CF3)3BCO is dissolved in CD3CN at room temperature CO is evolved and the acetonitrile adduct (CF3)3BNCCD3 is formed <2002JA15385>. (Dimethylamino)bis(trifluoromethyl)borane (CF3)2BNMe2 22 reacts with N-sulfinylcarboxamides RC(¼O)N¼S¼O by [2+4]-cycloaddition leading to 23 and with N-sulfinylcarbamates ROC(¼O)N¼S¼O by concomitant [2+4]- and [2+2]-cycloaddition leading to 24 and 25, respectively, cf. Scheme 5 <2002ZAAC(628)2299>.

ClF

NH4[B(CN)4]

R C N

ClF

HF

K[B(CF3)4] HF

NCl2 R CF2

R CF3 + HNCl2

Scheme 4

O N RC(=O)N=S=O

R

S

NMe2 B(CF3)2

O 23

(CF3)2BNMe2 22

ROC(=O)N=S=O

O N RO

S O 24

O NMe2 B(CF3)2

S +

NMe2

N B(CF3)2 ROC(=O) 25

Scheme 5

6.07.2.3.3

Three halogens and a germanium function

Iodotris(trifluoromethyl)germane (CF3)3GeI is commercially available. The compound (CF3)GePh3 has been prepared from Ph3GeCl and (CF3)2Cdglyme <2000OM2603>. When CF3I is heated with GeBr4 and copper bronze at 180 C, tribromo(trifluoromethyl)germane (CF3)GeBr3 is formed <2001MI765>. The phosphaethene HP¼C(F)NEt2 has been converted into (CF3)3GeP¼C(F)NEt2 by treatment with (CF3)3GeI and Et3N <2000ZAAC(626)1141>. Displacement reactions of (CF3)3GeI and (CF3)2GeI2 with Hg(NSO)2 lead to (CF3)3GeNSO 26 and (CF3)2Ge(NSO)2 27, respectively. Compound 26 suffers loss of SO2 with formation of sulfur diimide (CF3)3GeN¼S¼NGe(CF3)3 28. The corresponding condensation of 27 leads to the medium sized heterocycle (CF3)2Ge(N¼S¼N)2Ge(CF3)2 29, cf. Scheme 6 <1999JFC(96)147>.

Functions Containing Four Halogens or Three Halogens

(CF3)3GeI

Hg(NSO)2

263

(CF3)3GeN=S=O 26

(CF3)2GeI2

Hg(NSO)2

CF3 S O N Ge N CF3 O S 27

(CF3)3GeN=S=O 26 CF3 S O N Ge N O S CF3

(CF3)3GeN=S=NGe(CF3)3 –SO2

–SO2

27

28

CF3 N S N CF3 Ge Ge CF3 N S N CF3 29

Scheme 6

6.07.2.4 6.07.2.4.1

Three Halogens and a Metal Function Trihalomethyl alkali and earth alkali metals, CHal3M (M = Li, Na, K, Cs, Mg)

A transient species, tentatively identified as (triiodomethyl)magnesium chloride (CI3)MgCl, has been observed in the reaction system triiodomethane–isopropylmagnesium chloride <2001OM5310>.

6.07.2.4.2

(Trihalomethyl)aluminum, -gallium, -indium, and -thallium compounds, CHal3MRn (M = Al, Ga, In, Tl)

Tris(trifluoromethyl)indium(III) (CF3)3In is available by cocondensation of trifluoromethyl radicals with indium vapor <1986MI701>. Phenylbis(trifluoromethyl)thallium(III) (CF3)2TlPh and bis(trifluoromethyl)thallium(III) acetate (CF3)2Tl(OAc) have been prepared from (CF3)2Cdglyme and PhTl(OAc)2 and Tl(OAc)3, respectively <1989IC2816>.

6.07.2.4.3

(Trihalomethyl)tin and -lead compounds, CHal3MRn (M = Sn(II), Sn(IV), Pb(IV))

The reaction of trimethyltin chloride Me3SnCl with solvent-free (CF3)2Cd gives a 90% yield of (CF2Cl)SnMe3 and (CF3)SnMe3 in a 2:1 ratio <1995JOM(503)C51>. The compounds (CF3)SnPh3, (CF3)2SnPh2, (CF3)PbPh3, (CF3)2PbPh2, and (CF3)3PbPh are available by treatment of the corresponding halo(phenyl)metal compounds with (CF3)2Cdglyme <2000OM2603>.

6.07.2.4.4 (Trihalomethyl)zinc, -cadmium, and -mercury compounds, CHal3MR (M = Zn, Cd,Hg(II)) The chemistry of (trifluoromethyl)zinc bromide (CF3)ZnBr, especially with regard to the preparation and utilization of complexes, has been reviewed <1996JPR(338)283>. Donor-free bis(trifluoromethyl)cadmium (CF3)2Cd is formed in quantitative yield from Et2Cd and CF3I <1995JOM(503)C51>. The mercury(I) compound CF3HgHgCF3 has not been observed yet in keeping with its theoretically predicted instability. Apparently other factors counteract the expectedly stabilizing effect of the strongly electronegative CF3 groups on the strength of the HgHg bond <1995JST(358)195>.

264 6.07.2.4.5

Functions Containing Four Halogens or Three Halogens (Trihalomethyl)copper, -silver, and -gold compounds, CHal3MRn (M = Cu(I), Cu(III), Ag(I), Ag(III), Au(I), Au(III))

Tris(trifluoromethyl)silver(III) (CF3)3Ag has been used as a starting material for heteroleptic argentates(III) containing trifluoromethyl groups. The anions tetrakis(trifluoromethyl)cuprate(III) [Cu(CF3)4], tetrakis(trifluoromethyl)argentate(III) [Ag(CF3)4], and tetrakis(trifluoromethyl)aurate(III) [Au(CF3)4], available by oxidation of lower-valency (trifluoromethyl)metal compounds, have been employed in the construction of superconducting BEDT-TTF salts <1999CCR(190192)781>. (Trifluoromethyl)gold(I) phosphine complexes (CF3)AuPR3 have been prepared from CF3SiMe3 and the corresponding alkoxides Au[OCH(CF3)2]PR3. The analogous reaction with CCl3SiMe3 leads to the corresponding labile products (CCl3)AuPR3. Starting from the gold(III) compound (CF3)Me2Au(OPh), CF3SiMe3, and a ligand PR3 the gold(III) complexes (CF3)Me2AuPR3 are obtained <2000ICA(309)151>.

6.07.2.4.6 Miscellaneous trihalomethyl transition metal compounds, CHal3MRn (M = transition metal) Attempts at oxidative addition of CCl4, CBr4, and CI4 to the Rh(I) complex RhCl(CO)(PPh3)(HNEt2) failed to yield the corresponding trichloromethyl-, tribromomethyl-, and triiodomethylsubstituted Rh(III) complexes, halogenation being observed instead <1998OM4966>.

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Functions Containing Four Halogens or Three Halogens 1993JFC(62)293 1993IC5007 1993JST(301)65 1994IC3281 1994JFC(66)193 1994JFC(67)91 1994JFC(69)219 1995AG(E)586 1995COFGT(6)211 1995IC3114 1995IZV150 1995JAP07179385

1995JAP07179386

1995JFC(70)45 1995JFC(70)255 1995JFC(73)17 1995JFC(73)273 1995JOC1319 1995JOM(503)C51 1995JPC12151 1995JST(358)195 1995MI8 1995SUP1381923 1995USP5382704 1995USP5446218 1995ZN(B)189 1996CB1383 1996JA8140 1996JFC(76)7 1996JFC(79)103 1996JFC(79)111 1996JOC7545 1996JPR(338)283 1996ZOB1715 1997IC2147 1997JA1572 1997JAP09020695 1997JCR(S)6 1997JCS(F)379 1997JFC(82)9 1997JOC6160 1997JST(407)171 1997T13933 1997TL65

265

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269

Biographical sketch

Alexander Senning Born 1936 in Riga, Latvia, Alexander Senning studied chemistry in Munich, Germany (1954–1959) and Uppsala, Sweden (1960–1962). He obtained a Ph.D. in organic chemistry from Uppsala University 1962, joined the Department of Chemistry, Aarhus University, Denmark as assistant professor (1962–1965) and served as associate professor during 1965–1993. During a sabbatical leave (1973–1975), he was head of the research laboratory of the drug company A/S Alfred Benzon, Copenhagen, Denmark. He joined the Danish Engineering Academy (DIA), Lyngby, Denmark, later part of The Technical University of Denmark (DTU), Lyngby, Denmark, as professor of organic chemistry in 1993, until his retirement in 2003. Research interests: organic sulfur chemistry, medicinal chemistry. Extensive activities as book and journal editor. A detailed chemical autobiography is available in Sulfur Rep., 2003, 24, 191–253.

Jørgen Øgaard Madsen Born 1940 in Aars, Denmark, Jørgen Øgaard Madsen studied chemistry in Aarhus, Denmark (1962–1971) and received an M.Sc. (1967) and a Ph.D. (1972) in organic chemistry from Aarhus University, Denmark. He held an assistant professorship at the Department of Chemistry, Aarhus University, Denmark (1967–1971) and joined the Department of Organic Chemistry (later Department of Chemistry) of the Technical University of Denmark (DTU) as associate professor (1972 to present). Research interests: heterocyclic enamines, stereospecific syntheses with baker’s yeast, natural product chemistry, analytical organic chemistry (HPLC, MS).

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 243–269

6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents G. VARVOUNIS and N. KAROUSIS University of Ioannina, Ioannina, Greece 6.08.1 INTRODUCTION 6.08.2 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS 6.08.2.1 Two Halogens and Two Oxygen Functions 6.08.2.1.1 Difluoro compounds 6.08.2.1.2 Dichloro and dibromo compounds 6.08.2.2 Two Halogens and Two Sulfur Functions 6.08.2.2.1 Difluoro compounds 6.08.2.2.2 Dichloro, dibromo, and diiodo compounds 6.08.2.3 Two Halogens, an Oxygen, and a Sulfur Function 6.08.2.4 Two Halogens and Other Chalcogen Functions 6.08.3 TWO HALOGENS AND ONE CHALCOGEN FUNCTION 6.08.3.1 Two Halogens, a Chalcogen, and a Nitrogen Function 6.08.3.1.1 Oxygen compounds 6.08.3.1.2 Sulfur compounds 6.08.3.2 Two Halogens, a Chalcogen, and Other Functions 6.08.4 TWO HALOGENS AND TWO GROUP V ELEMENT FUNCTIONS 6.08.4.1 Two Halogens and Two Nitrogen Functions 6.08.4.1.1 Diamines and their derivatives 6.08.4.1.2 Cyclic compounds 6.08.4.2 Two Halogens and Two Phosphorus Functions 6.08.4.2.1 Bis(phosphonates) 6.08.4.2.2 Cyclic compounds 6.08.4.2.3 Miscellaneous compounds 6.08.4.3 Two Halogens, a Nitrogen, and a Phosphorus Function 6.08.5 TWO HALOGENS AND ONE GROUP V ELEMENT FUNCTION 6.08.5.1 Two Halogens, a Phosphorus, and a Metalloid or Metal Function 6.08.5.2 Two Halogens, a Nitrogen, and a Metalloid Function 6.08.6 TWO HALOGENS AND TWO METALLOID FUNCTIONS 6.08.6.1 Two Halogens and Two Silicon Functions 6.08.6.1.1 Linear carbosilanes 6.08.6.1.2 Cyclic carbosilanes 6.08.7 TWO HALOGENS AND TWO METAL FUNCTIONS

271

272 272 272 272 274 274 274 277 278 278 279 279 279 280 280 281 281 281 281 282 282 284 285 287 288 288 289 290 290 290 291 292

272 6.08.1

Functions Containing Two Halogens and Two Other Heteroatom Substituents INTRODUCTION

Compounds or functionalities that consist of a central carbon atom attached to two halogens and two other heteroatoms that include chalcogens (O, S, Se, or Te), group V elements (N, P, As, Sb, Bi, B, Si, or Ge), main group metals (Sn, Pb, Al, Ga, In, Tl, Be, Mg, Ca, Sr, Ba, Li, Na, K, Rb, or Cs), and transition metals (Cu, Ag, Au, Zn, Cd, Hg, Ti, Zr, Hf, Cr, Mo, W, Mn, Fe, Co, Ni, Pd, or Pt) are generally rare. The most frequently encountered halogen is by far fluorine, with chlorine in the second place. One example of a mixed halogen is known whereas mixed heteroatoms are quite common. The most common heteroatom combinations are two oxygen, two phosphorus, and two sulfur atoms.

6.08.2

TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS

6.08.2.1

Two Halogens and Two Oxygen Functions

6.08.2.1.1

Difluoro compounds

Fluorocarbonylhypofluorite, FC(O)OF, is a relatively unstable product prepared in low yield from the UV irradiation of a mixture of F2 and bis(fluoroformyl)peroxide. The reactions of FC(O)OF have been limited to the preparation of difluorodioxirane, bis(fluoroxy)difluoromethane, and chloroxyfluoroxydifluoromethane <1995COFGT(6)249>. The yield of FC(O)OF was greatly improved by using a 12 W low-pressure UV lamp in place of a 350 W mediumpressure Hg lamp, as reported in the literature. Furthermore in the reaction of FC(O)OF with ClF, the yield of chloroxyfluoroxydifluoromethane was improved by using CsF doped with H2O instead of dry CsF <1995IC6221>. The chemistry of this compound has not yet been investigated. Difluorodioxirane is one of the most stable dioxiranes known. It was originally prepared by passing a 1:1 (v/v) mixture of FC(O)OF and ClF over a CsF catalyst <1995COFGT(6)249>. An improvement over this method has been achieved by using Cl2 and the new catalyst KHF2; difluorodioxirane was obtained in moderate but higher yields <1999CC1671>. The OO bond length in difluorodioxirane is 157.6 pm, and is the longest OO bond ever calculated and measured. This theoretically explains why it is a powerful oxidant and can readily undergo reactions that are typical of dioxiranes. It transfers oxygen to alkenes, forming epoxides and COF2 in high yield. Its reaction with 13COF2 in the presence of CsF was used to show that it reacts by ring opening of the OO bond (Equation (1)). A reasonable mechanistic proposal (Scheme 1) predicts trifluoromethoxy anion attack on the dioxirane peroxide bond to give CF3OOCF2O, which loses fluoride to form 1 or reacts further with dioxirane to form new oligomeric peroxides 2–4. The 13C distribution makes it clear that the predominant reaction is attack of CF3O on the dioxirane at oxygen and not at the more electropositive carbon.

F F

O O

+

13COF

CsF 3

70% 13C

–50 °C, 16 h

13CF

3OOC(O)F

67% 13C 10% 13C 1

+

13CF

3O(OCF2O)nOC(O)F

67% 13C

ð1Þ 7% 13C

2–4 (n = 1–3)

Bis(fluoroxy)difluoromethane reacts with tetrafluoroethylene and trans-1,2-dichloroethylene to give bisethers of formula (RO)2CF2. Bis(fluoroxy)difluoromethane also reacts thermally and photochemically with perfluoro Dewar benzene; the reaction products were mainly complex copolymer mixtures, whereas a structure containing 1,1-difluoro-1,3-dioxolane was isolated in 6% yield <1995COFGT(6)249>. Previous preparations of halogenated 2,2-difluoro-1,3-dioxolanes used multistep processes but often in low or inconsistent yields <1976USP3978030>. Later the addition of bis(fluoroxy)difluoromethane to halogenated alkenes (CX2¼CX2) gave a better yield of 2,2-difluoro-1,3-dioxolanes <1995COFGT(6)249>. This method was further improved by carrying out the reaction of bis(fluoroxy)difluoromethane with halogenated alkenes (CF2¼CFCF3, CF2¼CFOCF2CF3, CF2¼CHCF3, CF3CF¼CFCl, CFBr¼CFBr,

273

Functions Containing Two Halogens and Two Other Heteroatom Substituents

CCl2¼CCl2, CHCl¼CHCl, CH2¼CHCl, CF2¼CFCl, (CF3)2CFCF¼CFCF3, CF2¼CFBr, and CF2¼CF2) in the presence of halogenated inert solvents (CF2Cl2, CFCl3, and perfluoropolyethers) as well as in neat olefin. The halogenated 2,2-difluoro-1,3-dioxolanes were obtained in 43–95% yields, together with 1,2-difluorotetrahalogenoethanes as side products. Continuous, semicontinuous or batch procedures were used depending on the physicochemical properties of the olefin <1995JFC(71)111>.

13COF

13CF

2

– 3O

13CF

+ F–

O O

F

3O

–

13CF

–F–

–

3OOCF2O

13CF

3OOC(O)F

F

1 O n F OF 13CF

–F–

–

3(OCF2O)nOCF2O

13

CF3(OCF2O)nOC(O)F 2–4 (n = 1–3)

Scheme 1

4-(2,2-Difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile 5 is a fungicide which is metabolized by poultry into the N-hydroxy derivative. The latter has been synthesized in seven steps and 23% overall yield from 2,2-difluoro-1,3-benzodioxole-4-carboxylic acid 6 <1989EUP333685>. The 2,2-difluoro-1,3-benzodioxole ring remains intact throughout the synthesis <1995JOC4302>. 6,6-Difluoro-1,3-dioxolo[4,5-f]benzimidazole-2-thione 7 was converted into the 2-chlorodioxolobenzimidazole 8 by chlorine (Scheme 2) <2001GEP10005277>. Apparently 8 was also prepared by heating dioxobenzimidazol-2-one 9 with phosphoryl chloride under HCl. Compound 9 is an intermediate for the preparation of compounds with fungicidal activity <2001GEP10005277>. H N NC

CO2H O

F

O

F

H N

O

S F

N H

O 7

F

O

F

6

5

F

O

Cl2, MeOH, 0 °C

F

O

N

96%

F

O

N H

Cl 8

POCl3, HCl, ∆

F

O

85%

F

O

H N O N H 9

Scheme 2

2,2-Difluorobenzo[1,3]dioxole-4-carbaldehyde 13 (Scheme 3) was prepared in three steps from 4-methylbenzo[1,3]dioxole 10. The latter and 2,20 -azobisisobutyronitrile (AIBN) were heated with chlorine at 70 C and then at 150 C to induce chlorination to both C-2 and the methyl group. 4-Dichloromethyl-2,2-dichlorobenzo[1,3]dioxole 11 thus obtained was fluorinated by HF at 15 C to give 2,2-difluoro derivative 12, in high yield. Conversion of the CHCl2 group in 12 into an aldehyde group in 13 required heating in formic acid <1997EUP759433>.

274

Functions Containing Two Halogens and Two Other Heteroatom Substituents CHCl2

Me O

AIBN, Cl2

O

70 °C then 150 °C

CHCl2

O

Cl

O

Cl

Anhyd. HF, –15 °C

F

O

F

12

11

10

O

HCO2H 100 °C CHO O

F

O

F

13

Scheme 3

A process for producing fluorinated alkyl ethers 15 from fluorinated alcohols 14, by the action of HF in the presence of BF3, is claimed in a patent (Equation (2)) <1995USP5382704>. H R C OH R 14

R

HF, BF3, CCl4

R

C

H F H R C C O O R F 15

ð2Þ

R = CF2CF3, (CF2)2CF3, or (CF2)3CF3

6.08.2.1.2

Dichloro and dibromo compounds

The synthesis and reactions of these compounds remains an area very little investigated. Interest was focused in developing more efficient methods to synthesize dichlorodiphenoxymethane 17 and dichloroformals 19 <1995COFGT(6)249>. It has been claimed in a patent that the yield of 17 may be increased over the previous methods, by heating 16 in a mixture of PCl3 and POCl3 at 160–175 C, while passing chlorine into the reaction mixture (Equation (3)) <1998JAP10182538>. Another patent claims that TiCl4 as catalyst in the reaction between thionocarbonates 18 and SO2Cl2 increases the efficiency in the synthesis of dichloroformal derivatives 19, where R is CCl3, CF3, C(NO2)3, C(NO2)2Me, CF(NO2)2, CF2CF3, CF2NO2, or CCl(NO2)2 (Equation (4)) <1997USP5631406>. Ph O + PCl3 + POCl3

Cl2, 160–175 °C

PhO

Cl

91%

PhO

Cl

Ph

17

16 RCH2O S

+

SO2Cl2

RCH2O 18

6.08.2.2 6.08.2.2.1

ð3Þ

TiCl4

RCH2O

Cl

RCH2O

Cl

ð4Þ

19

Two Halogens and Two Sulfur Functions Difluoro compounds

Bis(trifluorothio)difluoromethane was first observed as a by-product in electrochemical fluorination (ECF) of carbon disulfide. Later it was shown that this compound could be prepared in high purity by direct fluorination of CS2. Oxidative additions to the SF3 groups and controlled BF3catalyzed solvolysis in liquid SO2 to give difluoromethanedisulfinyldifluoride 20 have been described. The chemistry of the latter with nitrogen nucleophiles has been investigated in detail

Functions Containing Two Halogens and Two Other Heteroatom Substituents

275

<1995COFGT(6)249>. This work has been extended to the preparation of difluoromethanebis(sulfinic acid) 21 by allowing moist air to come into contact with 20 for 3 weeks (Equation (5)). In this reaction no detectable amounts of the anhydride 23, expected as an intermediate, were found. Single crystals of the anhydride 23 were isolated after salt 22 was hydrolyzed slowly by traces of moisture while stored at 8 C (Equation (6)) <1998JFC(89)55>. O S F F S F O 20 F

–78 °C, 3 weeks

+

Cs [F2C(SF3)2F]

–

O S OH F S OH O 21 F

Moist air

Traces of moisture

F

8 °C, 2–3 weeks

F

ð5Þ

O S O

22

ð6Þ

S O 23

While ECF in anhydrous HF was used to prepare bis(fluorosulfonyl)difluoromethane from CH2(SO2F)2 <1997JFC(83)145>, the preparation of F2C(SO2Ph)2 required first the reaction of PhSO2CHF2 and NaOH in a two-phase system to give PhSO2CF2SPh, and second oxidation of the latter with H2O2 <1995COFGT(6)249>. Recently, F2C(SO2Ph)2 was prepared from PhSCHF2 by reaction with PhSO2Cl in the presence of aqueous NaOH, followed by oxidation of the product PhSO2CF2SPh with H2O2 <2002IC6118>. Bis(trifluoromethylsulfonyl)methane 24 was first prepared by reacting methylmagnesium halides with trifluoromethanesulfonylfluoride in Et2O <1956JCS173>. Later the synthesis was improved by simply replacing Et2O by THF. ECF of 24 in anhydrous HF gave difluoromethyl derivative 25 in 25% yield, together with 5% of CF3SO2F (Equation (7)) <1998JFC(91)9>. Compound 25 was first obtained in traces by the treatment of 26 with elemental fluorine <1994JFC(67)27>. Anhyd. HF, e–

H2C(SO2CF3)2

F2C(SO2CF3)2 + CF3SO2F

ECF

25 (25%)

24 O O S

ð7Þ

5%

O S O S

O

O 26

The condensation of BrCF2Cl with sodium thiophenoxides 27 gave bis(thiophenol)difluoromethanes 28 in good yields. The authors postulated an ionic mechanism for the reaction (Equations (8) and (9)) <1981TL1997>. 4-XC6H4SNa + BrCF2Cl

DMF, –40 °C

F

SC6H4X-4

X = Cl or NO2

F

SC6H4X-4

27

ð8Þ

28 –

4-XC6H4SCF2

+

28

4-XC6H4SBr X = Cl or NO2

ð9Þ

The related reaction of sodium thiophenoxide with BrCF2Cl in dimethyl formamide (DMF) at 40 C gave four products, the bromo and hydrogenated derivatives 29 and 30 and the chloro and bis(thiophenol)difluoromethane derivatives 31 and 32, in 60% overall yield (Equation (10)). Repetition of this reaction in the presence of nitrobenzene, a known inhibitor of electron-transfer processes, greatly reduced the yield of 32 (Equation (11)). This result indicates that 32 is formed through a radical chain mechanism. The condensation between dichlorodifluoromethane CF2Cl2

276

Functions Containing Two Halogens and Two Other Heteroatom Substituents

and sodium thiophenoxide under UV irradiation produced three products, 30 and 31 as minor products with 32 as the major product (Equation (12)). These facts strongly indicate that the reactions leading to 32 occur through a radical mechanism as depicted in Scheme 4 <1983JOC1979>. DMF

PhSNa + BrCF2Cl

–40 °C

29 (9%)

30 (3%) DMF

PhSNa + BrCF2C + PhNO2

+

PhSCF2Cl

CF2Cl2

DMF, –40 °C hν

–

–

31 (5%)

F

SPh

2%

32 (43%)

2%

ð11Þ

5%

30 + 31 + 32 6%

6%

ð10Þ

ð12Þ

22%

PhSCF2 + Cl–

PhSCF2 + PhS– PhSCF2SPh

SPh

29 + 30 + 31 + 32

–40 °C

52% PhSNa

F PhSCF2Br + PhSCF2H + PhSCF2Cl +

PhSCF2SPh

+ BrCF2Cl

–

PhSCF2SPh + BrCF2Cl

–

32

Scheme 4

The reaction of CF2Cl2 with PhSK 33a and 4-MeC6H4SK 33b in DMF under 2 atm pressure gave sulfides 34 as major products while 35 and difluoromethylbis(arylsulphides) 36 as minor products (Equation (13)) <1984CC793>. ArSK + CF2Cl2 33

DMF, 2 atm a, Ar = Ph b, Ar = 4-MeC6H4

ArSCF2Cl + ArSCF2H + 34a (62%) 34b (44%)

35a (8%) 35b (8%)

F

SAr

F

SAr

ð13Þ

36a (7%) 36b (6%)

The work on the reactivity of dichlorodihalomethanes with thionate anions has been extended to CF2I2. Sodium 4-chlorothiophenoxide 37 and CF2I2 react in a 2:1 ratio in diglyme at room temperature to afford bis(4-chlorothiophenol)difluoromethane 38 in 43% yield (Equation (14)). Repeating the reaction by changing the molar ratio of 37 to CF2I2 into 1:2 resulted in a drastic drop of the yield of 38 to 9% and the formation of two major products disulfide 39 and difluoromethane 40 (Equation (15)). Even better, 38 was formed in 60% yield by the action of 37 on 4-ClC6H4SCF2I in DMF <2000JFC(102)105>. 4-ClC6H4SNa + CF2I2 37

Diglyme

F

SC6H4Cl-4

ratio 2:1 43%

F

SC6H4Cl-4

ð14Þ

38 37 + CF2I2

Diglyme ratio 1:2

4-ClC6H4SSC6H4Cl-4 + 4-ClC6H4SCF2I + 38 39 (28%)

40 (35%)

ð15Þ

9%

Halogen exchange reactions occur when bis(pentafluorothiophenol)dichloromethane 41 is heated with SbF3, SbF5, or CsF. Reaction of 41 with an excess of SbF3 at 150 C gave dithiocarbonate 43 as the main product and small amounts of bis(pentafluorothiophenol)difluoromethane 44 and disulfide 42 (Equation (16)). The reaction of 41 with SbF5 at 90 C resulted in an increase in the formation of difluoromethyl derivative 44 but the main product was the disulfide 42. (C6F5S)2CClF, C6F5SCF3, and dithiocarbonate 43 were also identified among the

Functions Containing Two Halogens and Two Other Heteroatom Substituents

277

reaction products. At 225 C the reaction of 41 with excess anhydrous CsF without solvent gave difluoromethane 44 and polysulfides 46 as major products together with disulfide 42 and chlorofluoromethane 45 as minor products (Equation (17)). All these compounds were difficult to obtain pure so were identified by 19F-NMR and GC-MS data <1999JFC(98)17>. SbF3

(C6F5S)2CCl2

(C6F5S)2 + (C6F5S)2CO +

150 °C

41 41

42 (6%)

CsF

42 + 44

225 °C

+

43 (75%)

F

SC6F5

Cl

SC6H5

6.08.2.2.2

SC6F5

F

SC6H5

ð16Þ

44 (16%) F

SC6F5

X

S(C6F4S)nC6H5

+ 46

45

F

ð17Þ

X = Cl or F n = 1, 2, or 3

Dichloro, dibromo, and diiodo compounds

In this category of compounds, the major interest has been the synthesis and reactions of halogenated 1,1,3,3-tetraoxo-1,3-dithietanes, halogenated 1,1,3,3,5,5-hexaoxo-1,3,5-trithianes, halogenated [1,3]dithioles, [1,3]dithiole-1,1-dioxides, and [1,3]dithiole-1,1,3,3-tetraoxides, dichloromethanedisulfenyl chloride, and bis(alkyl or arylsulfonyl)dihalogenomethanes <1995COFGT(6)249>. An interesting rearrangement of chloromethylsulfenylchloride 47 into 1-adamantylsulfonyl dichloromethyl pentachlorophenyl disulfide 48 occurred when 47 was left in CHCl3 for a few days (Equation (18)). In addition, refluxing an ethereal solution of 47 led to a quantitative yield of thiosulfonate 49 (Equation (19)). These reactions are postulated to occur via concerted mechanisms supported by AM1 calculations and from an experimental point of view, as the reactions take place in solvents of low polarity <1994JCS(P1)1251>. O O R1 R1 S S CHCl , 5 d Cl 3 O Cl O C C S Cl S Cl S S R2 R2 48 47 R1 = 1-adamantyl, R2 = C6Cl5 O R1 S Cl O C S S R2 Cl

Et2O, ∆, 40 min

47

Cl

ð18Þ

Cl

O O S S S R2 R1 C

ð19Þ

49 R1 = 1-adamantyl, R2 = C6Cl5

Bis(substitutedsulfonyl)dihalogenomethanes for all four halogens have been known for over hundred years. Methods of synthesis include direct chlorination or bromination of gem-disulfones, halogenation of potassium salts of monohalogenated gem-disulfones, and the halogenation of benzeneiodonium ylides with halosuccinimides <1995COFGT(6)249>. An improved synthesis of bis(trifluoromethylsulfonyl)methane 50 was accomplished by the action of methylmagnesium chloride on trifluoromethanesulfonylfluoride. The reaction of N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), and N-iodosuccinimide (NIS) in carbon tetrachloride with 50 leads to the formation of the corresponding dihalogenomethanes 51 (Equation (20)) <1998JFC(91)9>. O H H

SO2CF3 SO2CF3

+ 2

N X

CCl4

X

SO2CF3

X = Cl, Br or I

X

SO2CF3

O 50

51a, X = Cl 76% 51b, X = Br 78% 51c, X = I 39%

ð20Þ

278

Functions Containing Two Halogens and Two Other Heteroatom Substituents

A study of the interaction of pentafluorothiophenol 52 and CCl4 in the presence of AlCl3 led to the conclusion that at room temperature, 60 C, or 80 C and irrespective of the amount of CCl4 and AlCl3 used, dichloromethane 53 was formed as the main product together with minor products chloromethane 54 and disulfide 55 (Equation (21)). The origin of observed products is depicted in Scheme 5. The stability of compound 53 toward hydrolysis or further reaction with starting material and compound 54 is attributed to the inefficient stabilization of the adjacent carbocationic center that is involved in these reactions <1999JFC(98)17>. C6F5SH

AlCl3, CCl4

Cl

SC6F5

Cl

SC6F5

52

+ (C6H5S)3CCl + (C6F5S)2

53

δ– δ+ C6F5SH + [CCl3...Cl...AlCl3]

C6F5SCCl3

AlCl3

ð21Þ

55

54

δ+ δ– C6F5SCCl2...Cl...AlCl3

Cl–

52 52

AlCl3

(C6F5S)2CCl2

δ– δ+ (C6F5S)2CCl...Cl...AlCl3

52

(C6F5S)3CCl

Cl–

53

54

Scheme 5

6.08.2.3

Two Halogens, an Oxygen, and a Sulfur Function

Earlier work on this category of compounds is represented only by MeOCCl2SCl synthesized by the addition of chlorine to either MeOC(S)SMe or MeOC(S)SSC(S)OMe or MeOC(S)SSC(S)OMe <1995COFGT(6)249>. Treatment of phenols or alcohols ROH with NaH, CS2, and then with MeI led to high yields of dithiocarbonates 55. Oxidative desulfurization–fluorination of dithiocarbonates 55 was carried out using tetrabutylammonium dihydrogentrifluoride (TBAH2F3) with NBS in CH2Cl2 to afford difluoro(methylthio)methylethers 56 (Scheme 6). Methyl ethers 56 were converted readily into trifluoromethyl ethers ROCF3 by reaction with 70% HF in pyridine and 1,3-dibromo-5,5dimethylhydantoin <2000BCJ471>. S R

O

F

TBAH2F3 SMe

NBS, CH2Cl2

55

R 4-MeC6H4 4-PrnC6H4 4-BrC6H4CH2CH2 PhCH2CH2CH2 n-C16H33 4-PhC6H4 4-(4-BrC6H4)C6H4

F

R O

SMe 56

Yield (%) 64 58 19 15 9 23 28

R 4-n-C6H13C6H4 4-MeOC6H4 4-PhCH2OC6H4 4-PrnOC(O)C6H4 3-MeOC(O)C6H4 4-BrC6H4

Yield (%) 36 33 43 42 32 43

Scheme 6

6.08.2.4

Two Halogens and Other Chalcogen Functions

Tetrahalogeno 1,3-diselenetanes, 1,3-ditelluretanes, and 1,3-selenatelluretanes are known, most common being the tetrafluoro derivatives. Iodo derivatives are unknown <1995COFGT(6)249>. Several difluoro(phenylseleno)methylethers 60 have recently been reported. Difluoromethylbenzene selenide 57 was prepared by the treatment of diphenyl diselenide with NaBH4 in a 2:1 ratio of

Functions Containing Two Halogens and Two Other Heteroatom Substituents

279

EtOH/DMF and then with CF2Br2. Oxidation of 57 led to the formation of oxide 58 (Scheme 7). Compound 58 was reacted with acetic anhydride in the presence of cyclic ethers 59 in refluxing CH2Cl2 to give difluoro(phenylseleno)methyl compounds 60 (Equation (22)). The reaction of selenoxide 58 with Ac2O and (4-MeOC6H4Se)2 in THF provided AcOCH2CH2CH2CH2OCF2SePh and AcOCH2CH2CH2CH2OCF2SeC6H4Me-4 <1995JOC370>.

(PhSe)2

i. NaBH4, EtOH, DMF

F2HCSePh

ii. CF2Br

O

H2O2, CH2Cl2

F2HCSePh

57

58

Scheme 7

Z 58 +

R

Ac2O, CH2Cl2

n

H 59

6.08.3

F

Z(CH2)nCH(R)OAc

F

SePh 60

R

Z

n

Yield (%)

Me H H Me H H

O O O O O S

1 2 3 3 4 3

34 60 87 56 74 53

ð22Þ

TWO HALOGENS AND ONE CHALCOGEN FUNCTION

6.08.3.1

Two Halogens, a Chalcogen, and a Nitrogen Function

6.08.3.1.1

Oxygen compounds

Several compounds of the general formula X2C¼N-R (where X is F or Cl and R = F, Cl, CF3, or CF2CFClY where Y is F, Cl, or Br) proved to be good electrophiles. They reacted with substrates such as FSO2OX, F5SOCl, and F3CO2H to give the corresponding addition products FSO2OCF2NFX, F5SOCCl2NCl2, F3COOCF2NHCF3, and F3COOCF2NHCF2CF2CFClX (where X = F, Cl, or Br). The synthesis and reactions of 3,3-difluoro-3-(trifluoromethyl or pentafluorothio)oxaziridines have also been described <1995COFGT(6)249>. The difluorocarbimide double bond in 61 is saturated in 20 min at room temperature by SF6OCl to give difluoromethane derivative 62 (Scheme 8). The reaction of difluorocarbimide 64 with (CF3)3COCl is much slower and requires 1 day to give difluoromethane derivative 65 (Scheme 9). Irradiation of 62 and 65 gives rise to tetrazanes 63 and 66, respectively <1995IC5049>.

CF3(C3F7)NN=CF2 + SF5OCl

OSF5 Cl F N N F3C CF3

20 min

61

OSF5 C3H7 N N CF3 F N OSF5 F3C N C F C3H7 F F

F

hν

62

63

Scheme 8

1 day (CF3)2NN=CF2 + (CF3)3COCl 64

OC(CF3)3 Cl F N N F3C CF3 65

Scheme 9

OC(CF3)3 CF3 N N F CF3 N C OC(CF3)3 F3C N F F F3C F

F

hν

66

280

Functions Containing Two Halogens and Two Other Heteroatom Substituents

6.08.3.1.2

Sulfur compounds

Representatives of this category of compounds are F5SCF2NF2, FSCF2NF2, Et3N+CF2SO2, R+CF2SCF2SO2 (where R is quinucidine), and FCl(SCl)NCS <1995COFGT(6)249>. Isocyanatodifluoromethanesulfonyl fluoride 69 was prepared in good yield from azidocarbonyldifluoromethanesulfonyl fluoride 68, which was obtained by the reaction of sodium azide with chloroformyldifluoromethanesulfonylfluoride 67 (Scheme 10). Compound 69 is extremely sensitive to moisture. Autocatalytic fragmentation is observed with water (Scheme 11) <1997JFC(84)135>. Cl O

CCF2SO2F

NaN3

N3 O

67

∆

CCF2SO2F

F

N=C=O

F

SO2F 69

68

Scheme 10

69

HOOCNHCF2SO2F

–CO2 –HF

HN=CFSO2F

N C OS

N CSO2F

–HF

F O

Scheme 11

6.08.3.2

Two Halogens, a Chalcogen, and Other Functions

Generally, work on this category of compounds is very limited. Most of it is focused on difluoromethanes (such as F3CPHCF2OMe and C2F5PHCF2OMe) derived respectively from F3CP¼CF2 and C2F5P¼CF2 by the addition of methanol. Sulfinic salt (EtO)2P(O)CF2SO2Na was formed from (EtO)2P(O)CF2Br and sodium sulfite or sodium dithionite, and PhSO2CX2HgPh was synthesized by the addition of the anion of halogenated sulfones PhSO2CHX2 to PhHgCl (where X is Cl or Br) <1995COFGT(6)249>. Recently, the reaction of polyfluorinated ether 70 with hexaethylphosphorus triamide (HEPT) and chlorotrimethylsilane in benzonitrile as solvent was described to give the stable silane 71, in a reaction where the silyl ether was used as a transfer reagent (Equation (23)) <1995IC13>. PhCN

C6F5OCF2Br + HEPT + Me3SiCl

F

OC6F5

F

SiMe3

ð23Þ

70 71

Phenyl(trimethylsilyl)difluoromethyl sulfide 73 can be prepared in 85% yield by the reaction of bromodifluoromethylphenyl sulfide 72 with magnesium metal and Et3SiCl in DMF at 0 C. Sulfide 73 was oxidized with 3-chloroperoxybenzoic acid (m-CPBA) in dichloromethane to afford sulfone 74 (Scheme 12) <2003JOC4457>. PhSCF2Br + Me3SiCl

Mg

F

SPh

DMF

F

SiMe3

72

+ PhSSPh 73 85% m-CPBA CH2Cl2, 0 °C 51% F

SO2Ph

F

SiMe3 74

Scheme 12

Functions Containing Two Halogens and Two Other Heteroatom Substituents 6.08.4

281

TWO HALOGENS AND TWO GROUP V ELEMENT FUNCTIONS

6.08.4.1 6.08.4.1.1

Two Halogens and Two Nitrogen Functions Diamines and their derivatives

Representatives of this class of compounds are quite large in number. Difluoromethyldiamines, RNCF2NR1, were prepared by the addition of fluorine and cesium fluoride or chlorine to the nitrile function of cyanamides R3NCN. Addition of SF4, F4SO, Br2, and HgF2 or Cl2 and HgF2 to the latter has produced sulfur containing amine derivatives. Dihalogenodinitromethanes CX2(NO2)2 are derived from the treatment of PhI¼C(NO2)2 with Cl2, Br2, NCS or NBS, difluorodiazirine with N2O4 under UV irradiation, and Br2C(NO2)2 by reaction with ammonia and then with chlorine. UV irradiation of polyhalogenated diamines such as (CF3)2NCF2R produced the corresponding difluoromethylene gem-diamines. (Me2N)2CF2 was prepared by fluorinating tetramethylchloroformaimidinium chloride with KF in CH3CN. Bis(dialkylamino)difluoromethanes, (R2N)2CF2, are easily available via chlorination of tetraalkyl urea derivatives with oxalyl chloride followed by the fluorination of (R2N)2CCl+Cl salts with KF in CH3CN or 1,3dimethyl-2-imidazinone solutions <1995COFGT(6)249>. Recently, bis(dialkylamino)difluoromethanes have been used as precursors for fluorinated hexaalkylguanidinium salts. For example, the reaction of (Me2N)2CF2 75 with (dimethyl- or diethylamino)trimethylsilanes in CH3CN afforded the salts 76 (Equation (24)) <1999EUPO949226, 2002IC6118>. F F

NMe2

R2NSiMe3

NMe2

R = Me or Et

+

[(Me2N)2CNR2] [Me3SiF2]

–

ð24Þ

76

75

Previously 75 was formed by treating tetramethyl urea with COF2 in the presence of NaF <1995COFGT(6)249>. Recently a high-yield preparation of 75 involved the straightforward fluorination of salt 77 using anhydrous Me4NF in dichloromethane (Equation (25)). Compound 75 reacts with Me2NSiMe3 in CH3CN to give hexamethylguanidinium chloride, (Me2N)3C+F, which in turn reacts with Me3SiCF3 in monoglyme to provide easy access to (Me2N)3CCF3 <2000JFC(103)159>. (Me2N)2CCl+ Cl–

+

M4NF

CH2Cl2, 0 oC

F

NMe2

95%

F

NMe2

77

6.08.4.1.2

ð25Þ

75

Cyclic compounds

In this category of compounds three-, five-, and six-membered halogenated azirine, 1,3-diazolidine, and 1,3,5-triazolinane derivatives are known. Difluoroazirine, for example, was prepared by the reaction of Bu4N+I on F2C(NF2)2 <1995COFGT(6)249>. Halogen exchange between 2-chloro-1,3-dimethylimidazolinium chloride 78 and NaF in CH3CN gives the difluoroimidazolidine 79 in 77% yield (Equation (26)) <1999EUP895991>. A similar preparation of 79 uses KF and 1,3-dimethyl-2-imidazinone as solvent in the reaction with 78 (Equation (26)) <1999EUP895991, 1999EUPO949226, 2000JAP(K)200053650, 2002IC6118>. Me N H N Cl.HCl Me 78

NaF, MeCN, 80 °C

Me N F

Me N

N F Me

or KF,

O, 85 °C N Me

79

ð26Þ

282

Functions Containing Two Halogens and Two Other Heteroatom Substituents

Difluoroimidazolidine 81 was prepared from 1,3-bis(2-methoxyethyl)-2-imidazolidinone 80 upon reaction with oxalyl chloride at 40 C, followed by AgF in CH3CN at 50 C (Equation (27)) <2002JAP(K)2002322156>. O O

N

i. (COCl)2, 40 °C

N

O

ii. AgF, MeCN, 50 °C

HO

F

F

N

N

80

OH

ð27Þ

81

2-Chloro-1,3-dimethyl-2,3-dihydro-1H-benzoimidazole 82 was converted into the difluoro derivative 83 with KF at 85 C (Equation (28)). Compound 83 is an efficient fluorinating agent used to transform benzyl alcohol, at ambient temperature, into benzyl fluoride in 54% yield <2001JAP(K)2001322984>. Me N Cl

Me N F

KF, 85 °C

N F Me

N H Me

ð28Þ

83

82

Cyclic difluoro gem-diamines 79 and 81 are efficient fluorinating agents. Compound 79 was used in the fluorination of cyclohexanone into 1,1-difluorocyclohexane (20%) and 1-fluorocyclohexane (68%) <2002PCT0266409>, of thioester PhCS(OMe) into the a,a-difluoroether PhCF2(OMe) in 89% yield <2002JAP(K)200215015>, and of 2-trimethylsiloxyoctane into 2-fluorooctane in 91% yield <2002JAP(K)2002104999>. Furthermore, compound 81 converted 1-octanol into n-octylfluoride in 81% yield <2001JAP(K)2002322156>. Difluoromethane 79 when reacted with (dimethyl- or diethylamino)trimethylsilane in CH3CN at 30 C gave (2-dialkylamino)-1,3dimethylimidazolinium trimethyldifluorosiliconates 84 in high yield (Equation (29)) <2002IC6118>. Me N F N Me

F

79

6.08.4.2 6.08.4.2.1

R2NSiMe3 MeCN, –30 °C R = Me or Et

Me N +

NR2[Me3SiF2]–

N Me

ð29Þ

84

Two Halogens and Two Phosphorus Functions Bis(phosphonates)

The interest in this category of compounds rests upon (dichlorophosphonomethyl)phosphonic acid Cl2C(PO3H2)2, a substance used in the treatment of increased bone resorption and malignant hypercalcemia, and also upon the diverse biological properties of ATP analogs. A general route to (dihalogenophosphonomethyl)phosphonic acids X2C(PO3H2)2 is halogenation of appropriate tetraesters H2C(PO3R2)2 to give (dihalogenophosphonomethyl)tetraesters X2C(PO3R2)2. Although for the hydrolysis step heating in concentrated hydrochloric acid was widely used, conversion of tetraesters X2C(PO3R2)2 into silyl derivatives X2C(PO3-TMS2)2, and hydrolysis with water was more convenient. Mixed tetraesters containing silyl esters were also synthesized in order to selectively hydrolyze the silyl ester groups. However, little is known about selective preparation of partial methylbis(phosphonate esters), due to the difficulties in obtaining pure compounds having exactly one, two, or three ester substituents. Nucleoside analogs have resulted from the coupling of X2C(PO3H2)2 with 50 -phosphoromorpholidate of adenosine. By an analogous manner, the CF2 analog of 30 -azido-3-deoxythymidine triphosphate was obtained. Several other nucleoside analogs were reported <1995COFGT(6)249, 1995T6805>. A general and selective method for the synthesis of dichloromethylbis(phosphonic acid) partial alkylesters 86 and 87 from tetraesters 85 makes use of tertiary or secondary amines as dealkylating reagents (Scheme 13) <1996TL3533>. The degree of demethylation was found to depend on

Functions Containing Two Halogens and Two Other Heteroatom Substituents

283

the type of amine and the length of the alkyl chains in the amine used. Treatment of tetraesters 85 (where R1 = R2 = R3 = R4 = Me and R1 = R2 = Pri, R3 = R4 = Me) with Bu3N at 50 C led to the formation of the corresponding partial esters 86 (where Z+ is Bu3N+Me) in quantitative yield. Treatment of tetraesters 85 (where R1 = R2 = R3 = R4 = Et, Pri, or Hex) with pyridine at 115–120 C afforded the respective partial esters 86 (where Z+ is C5H5N+Et, C5H5N+Pri, or C5H5N+(n-C6H14)) in 80–85% yield. Reaction of tetraesters 85 (where R1 = R2 = R3 = R4 = Me, Et, or allyl, and R1 = R2 = Bu or Et, R3 = R4 = Pri or Me) with piperidine at 105–110 C resulted in the formation of the corresponding partial esters 87 (where Z+ is C5H10N+H) in yields ranging from 36% to 100%. When tetraesters 85 (where R1 = R2 = R3 = R4 = Me, Et, Pri, n-C5H12, cyclopentane, or n-C6H14) were heated at 105–110 C with morpholine, the corresponding partial esters 87 (where Z+ is O(CH2CH2)2N+H) were formed in 20–80% yields. The mechanism of the reaction can be understood by considering that the tetraester acts as an N-alkylating agent (Equation (30)).

O Cl

OR1 P

OR2 OR3

C Cl O

O

P

O–

Z

R3N

Cl

MeCN

Cl

OR1 P

OR2 OR3

C O

+

86

O

P

R2NH

Cl

MeCN

Cl

OR1 P

C O

OR4 85

P

O– Z+ OR3 O– Z+

87

Scheme 13

O OR3 P O R4

R N R R'

O– OR3 P O

MeCN

+

R + R4 N R R'

ð30Þ

The synthesis of partial esters 91 uses tetraalkylesters 88 as starting materials (Scheme 14). Tetraester 88 (where R is Me) was treated with Bu3N while the other three were treated with pyridine to give ammonium salts 89. The latter are converted into the corresponding sulfonic mixed ‘‘anhydrides’’ 90 by reaction with mesyl chloride, and then treated with aqueous base in acetone to precipitate partial esters 91. The reaction mechanism of these products can be tentatively rationalized as depicted in Scheme 15. The obtained ammonium cation, R3N+R0 , possesses a very powerful election-withdrawing effect that probably attracts the chlorine of MsCl thus facilating sulfonation at PO. In the resulting intermediate, the POR bond is additionally weakened by the MeSO2-moeity allowing easy cleavage of the POR bond by the chlorine anion of the ammonium salt that leads to the product <1996TL3533>.

O Cl

OR P

C Cl O

P

OR OR

O Bu3N

Cl

OR P

C

or pyridine

Cl O

OR

88

P

O MeSO2Cl

OR OR

O

O– Z+ R

O Cl

or NaOH, H2O

Cl

P

OR OSO2Me O– Z+R

90

OR P

OR O–Na+

C O

OR P

C Cl

89

NaHCO3, H2O

Cl

P

O– Na+ 91

+

+

+

+

+

R = Me, Et, Pri, or n-C6H14; Z R = Bu3N Me, C5H5N Et, C5H5N Pri, or C5H5N n-C6H14

Scheme 14

284

Functions Containing Two Halogens and Two Other Heteroatom Substituents O Me S Cl R O – O + O R N R P R' O R

O Me O S O O P R + O R Cl– R N R R'

O Me S O O O R P + R N R O– R'

–RCl

Scheme 15

Two nonnucleoside triphosphate analogs 96 and 97 were synthesized as substrates for terminal deoxynucleotidyl transferase. Their preparation required activation of fluorenylmethoxycarbonylaminoethylphosphonic acid (Fmoc–aminoethyl–phosphonic acid) 92 by 1,10 -carbonyldi(1,2,4-triazole) 93 in DMF and then addition of MeOH followed by bis(tri-n-butylammonium)difluoromethylenediphosphate 94 to give ammonium salt 96 or bis(tri-n-butylammonium)dibromo-ethylenediphosphate 95 to give ammonium salt 97 (Scheme 16) <2000MI1787>. O N i.

N N

N

N N , DMF

93 ii. MeOH FmocNHCH2CH2P(OH)2 O 92

O– O– iii. [Bu3NH]2[F2CHOP O POH] 94 O O O– O– + or [Bu3NH]2[Br2CHOP O POH] 95 O O +

OH OH O– + FmocNHCH2CH2P O P X P O– [Bu3NH]2 O O O 96, X = F2C (15%) 97, X = Br2C (16%)

Scheme 16

6.08.4.2.2

Cyclic compounds

Diphosphiranes (X2CP(R)P(R)) were produced by reacting ylides (Ph3P+CX2) with Ph3P, and by reacting trans-diphosphene (ArPPAr) with dichloro and dibromocarbenes (CHX3) in the presence of KOH. 1,3-Diphosphetanes X2CP(R)P(R)CX2 have been prepared by treating Cl2PCHCl2 with Et3N; by thermolysis of Me3SnP(CF3)2 gave, along with 1,3-diphosphetane F2CP(CF3)P(CF3)CF2, the trimer 2,4,6-tris(trifluoromethyl)-1,3,5-triphosphorin; and by heating Me2NP(SnMe3)CF3 at 500–600 C at 0.001 torr. 1-t-Butyl-2,4-dichloro-3,3-difluoro[1,2,4]azadiphosphetidine was prepared from the reaction of Cl2P(S)CF2P(S)Cl2 and butylamine <1995COFGT(6)249>. 1,2-Dihydro-1,3-diphosphetes 99 were formed as formal [2+2]-cycloaddition products by the reaction of perfluoro-2-phosphapropene 98 with phosphalkynes of the type RCP. Instead of the not isolable aminophosphalkynes Me2NCP and Et2NCP, the precursors HP¼C(F)NR2 were successfully used as synthetic equivalents (Equation (31)) <1997JOM(529)177>. F F

PCF3

+

RC P or HP C(F)R

F –78 °C

F

P P

R

98

99 R

= But,

Me2N, Et2N, or

CF3

Pr2i N

ð31Þ

Functions Containing Two Halogens and Two Other Heteroatom Substituents

285

Treatment of dichloromethane derivative 100 with 1 equiv. of N,N0 -dimethyl-N,N0 -bis(trimethylsilyl)urea 101 at low temperature led to the formation of 1,5-diaza-2,4-diphosphorinane6-one 102 (Equation (32)). Further reaction of 102 with another equivalent of 101 resulted in the formation of a mixture of symmetric bicyclic products 103 and 104. It was found that compound 103 rearranges slowly into thermodynamically more stable 104 (Scheme 17) <1993HAC565>.

O

O Cl

PCl2

Cl

Me

Me N SiMe3

N Me3Si

+

PCl2

–15 °C

Cl

N P

N P

Cl

Cl

101

100

–2Me3SiCl 20 °C Me

Me

ð32Þ

Cl

102

N Me 102 + 101

–2Me3SiCl

Me

Me

N O P Cl P N Cl N

O Me Rearrangement Me

Me

Me N N P Cl P N Cl N

Me

O

O 103

104

Scheme 17

The substitution of the chlorine atoms bonded to phosphorus in 102 by fluorine, alkoxy, or phenoxy groups could be realized with the formation of the corresponding P,P0 -disubstituted derivatives 105 (Equation (33)) <1993HAC565>. O Me Cl

O

N P

N P

Cl

Cl

Me Cl

Me R

N P

N P

Cl

Cl

102

Me R

ð33Þ

105 R = F, MeO, EtO, PriO, or PhO

When compound 102 was allowed to react with catechol, 2,3-dihydroxynaphthalene, tetrabromocatechol, resorcinol, saligenin, or 3,5-di-t-butylcatechol in the presence of Et3N, bridged compounds 106 to 110 were formed (Scheme 18). Whereas the catechol derivative 106, the naphthol derivative 107, and the tetrabromocatechol derivative 108 could be easily obtained, the saligenin derivative 109 and the 3,5-di-t-butylcatechol derivative 110 were found to be stable only in solution. The reaction of 102 with 1,2,4,5-tetrahydroxybenzene led to the pentacyclic derivative 111. In addition, reaction of hydroquinone with 102 afforded the polycyclic structure 112 (Scheme 18) <1997HAC165>. During the first hours, reaction between 113 and 101 produced a mixture of products 114 and 115 that were found by NMR spectroscopy to be in the ratio 10:1. Isomer 114 rearranged after 6 days into isomer 115 (Scheme 19) <2002ZAAC(628)1903>.

6.08.4.2.3

Miscellaneous compounds

In this category the phosphorus atoms of linear compounds R-PCX2P-R are substituted by various atoms or groups. For example, Cl2P(S)CF2P(S)Cl2 was treated with PriOH, SbF3, TMSNMe2, and PhPCl2 to afford the corresponding derivatives (PriO)2P(S)CF2P(S)(OPri)2,

286

Functions Containing Two Halogens and Two Other Heteroatom Substituents O Me O

O

N P

N P

Cl

Cl

Me

Me

O

N N P P O Cl Cl O

Me Me O P N

Cl Cl

O Me

Cl

Cl

P N

P N

OH

106

O

OH

OH

OH

Me

O 112

Br

OH

Br Br

OH

HO

OH

Br

OH OH

Br Br Br

O Me

Me

OH

OH

OH

Me

O Me

Me

O O P P Cl Cl N N

O

OH

But

O

O P N Me

108

But

N N P P OCl Cl O

Me O P N Cl Cl

Br

102 HO

O

O P N Me 107

OH

N N P P OCl Cl O

N N P P O Cl Cl O

Me

Me 109

Me But

O 111

But 110

Scheme 18

N Cl

Cl

Cl

P Cl

O

P Cl

Cl

+

Me

Me Me

N Me3Si

N SiMe3

–2Me3SiCl

N P

O P

Cl Cl

113

O Me Rearrangement Cl

Cl 114

101

Me N P

Cl

N P

Me Cl

Cl

Cl 115

Scheme 19

F2PCF2PF2, (Me2N)2PCF2P(NMe)2, and Cl2PCF2PCl2. Dialkylphosphines R2PH reacted with monomeric F2C¼PCF3 to give R2PHCF2PHCF3 derivatives, which upon heating with elemental sulfur afforded R2P(S)CF2PHCF3 derivatives <1995COFGT(6)249>. Trifluoromethyl-1,3-diphosphane 117 is formed regioselectively in almost quantitative yield by the addition of t-butylphosphane to perfluoro-2-phosphapropene 116 as a mixture of two diastereoisomers (Scheme 20). Compound 117 reacts with nickel tetracarbonyl to give the binuclear complex 118 as the only isolable product. The mixture contains four of the eight possible isomers. One of them was isolated in pure form by crystallization from n-pentane and its structure deciphered by X-ray crystallography (Equation (34)) <1993ZN1203>.

Functions Containing Two Halogens and Two Other Heteroatom Substituents F3CP=CF2 + ButPH2

287

But(H)PCF2P(H)CF3

116

117 But

Bu

t

F

P H

F

P H

F

P H

F

P H

F3C

F3C

But

But

F

P H

F

P H

F

P H

F

P H

F3C

F3C (S ),(R )/(R ),(S )-racemate

(R ),(R )/(S ),(S )-racemate

Scheme 20

117

Ni(CO)4 –2CO

F FH F 3C P Ni(CO)2 H P P H (OC)2Ni CF3 P F HF

ð34Þ

118

Reaction of compound 100 with catechol and Et3N led to the formation of compound 119 involving two benzodioxaphospholane rings connected via a CCl2 group (Equation (35)).

Cl Cl

OH

PCl2 PCl2 100

+ OH

Et3N

Cl O P C P O Cl O O

ð35Þ

119

Reaction of 119 with 1 equiv. of tetrachloroorthobenzoquinone 120, led to the formation of a mixture of 121, 122, and 123. The insolubility of isomer mixture 122/123 enabled easy separation from 121, but neither of the two structures could be assigned unambiguously to one isomer (Scheme 21) <1997CB1479>.

6.08.4.3

Two Halogens, a Nitrogen, and a Phosphorus Function

(E)/(Z)-2,2,4,4-Tetrafluoro-1,3-bis-trifluoromethyl[1,3]diarsetane and 2,2,4,4,6,6-hexafluoro-1,3,5tris-trifluoromethyl[1,3,5]triarsinane were two compounds obtained when Me3SnAs(CF3)2 was thermolyzed <1995COFGT(6)249>. Reductive debromination of N-bromodifluoromethyl4-dimethylaminopyridinium bromide 124 with tetrakis(dimethylamino)ethene (TDAE) lead to carbanionic species 125, which in the presence of Ph2PCl and Me3SiOTf provided the water soluble 1-(difluorodiphenylphosphanylmethyl)-4-dimethylaminopyridinium triflate 126 in 67% yield (Scheme 22). The imidazole-N-difluoromethylanion 128 was generated in situ from 1-bromodifluoromethylimidazole 127 using (Et2N)3P under Marchenko–Ruppert reaction conditions and trapped in the presence of Ph2PCl to afford (imidazol-1-yl)difluoromethyldiphenylphosphine 129 in 78% yield (Scheme 23) <2001JFC(109)173>.

288

Functions Containing Two Halogens and Two Other Heteroatom Substituents Cl

Cl

Cl Cl Cl

O Cl O O P C P O O O Cl

O

Cl Cl

O Cl

121

120

119

Cl

Cl

Cl Cl

Cl

Cl

Cl

Cl O O O O P C P O O O Cl O

Cl O O Cl O O P C P O O Cl O O

or Cl

Cl

Cl Cl

Cl

Cl Cl

Cl 123

122

Scheme 21

+

Me2N

NCF2Br

TDAE

+

–

Me2N

N CF2

Br– 124

i. Ph2PCl, TDAE

+

Me2N

ii. Me3SiOTf

NCF2PPh2

–OTf

126

125

Scheme 22

N N CF2Br 127

P(NEt2)3

N

–

N CF2 128

Ph2PCl

N N CF2PPh2 129

Scheme 23

6.08.5 6.08.5.1

TWO HALOGENS AND ONE GROUP V ELEMENT FUNCTION Two Halogens, a Phosphorus, and a Metalloid or Metal Function

In this category, various phosphonates and their salts such as Cl2C(TMS)P(O)(OEt)2, (TMS)(Cl or F)2CP(O)(OEt)2, (Bu3Sn)F2CP(O)(OEt)2 PhHgCF2P(O)(OEt)2, (Li+ or BrCd+)CX2P(O) (OEt)2, (BrCd+ or BrZn+)CF2P(O)(OEt)2, and (Cd2+)[CF2P(O)(OEt)2]2 have been synthesized <1995COFGT(6)249>. The silylated phosphonate (Me3Si)CF2P(O)(OEt)2 132 was readily prepared in 92% yield by direct silylation of (Br)CF2P(O)(OEt)2 130 using n-BuLi and Me3SiCl in THF at 78 C <1996T165>. Under similar reaction conditions, 130 was treated at low temperature in THF with PriMgCl (Scheme 24). This magnesium–bromine exchange reaction gave organomagnesium compound 131 that was stable for several days at low temperature. Compound 131 is more stable than the organolithium analog (Li+)F2CP(O)(OEt)2 133, when by contrast the organocadmium (BrCd+)CF2P(O)(OEt)2 134 and the organozinc (BrZn+)CF2P(O)(OEt)2 135

Functions Containing Two Halogens and Two Other Heteroatom Substituents

289

compounds are stable even at room temperature. With Me3SiCl, magnesium reagent 131 was converted into the silylated compound 132 in 90% yield <1997JOM(529)267>. Compound 132 was prepared less efficiently by electrochemical reduction of 130 in DMF and Me3SiCl, using a zinc anode at a current density of 10 mA cm2 <1997JFC(85)127>.

Br

F C P(OEt)2 F O

PriMgCl THF, –78 °C

F ClMg C P(OEt)2 F O 131

130

Me3SiCl, THF –78 °C

90% Zn anode, 2e, Me3SiCl, DMF 40%

Me3Si

F C P(OEt)2 F O 132

Scheme 24

Salt (Li+)CF2P(O)(OEt)2 133 was used on route to prepare (a,a-difluoroalkyl)phosphonates <1993JOC6174>, 50 -deoxy-50 -difluoromethylphosphonate nucleotide analogs <1995JOC2563>, and 1,1,6,6-tetrafluorohexane-1,6-bisphosphonic acid <2000HAC470>. Salt (BrCd+)CF2P(O)(OEt)2 134 underwent CuCl coupling with aryl iodides to give (a,a-difluorobenzylic)phosphonates <1996TL2745>. Mimetic L-4-[diethylphosphono(difluoromethyl)]phenylalanine derivatives were prepared from appropriately protected L-4-iodophenylalanine by esterification with diazomethane followed by a CuCl-mediated coupling with 134 <1997T11171>. Salt (BrZn+)CF2P(O)(OEt)2 135 was regioselectively cross coupled in a CuBr-mediated medium with methyl 2,5-diiodobenzoate <1999BMCL3109>, with various iodobenzene derivatives but with sonication <2000JCS(P1)2591>, and with -halo-,-unsaturated carboxylic acid derivatives <2000JOC4888>.

6.08.5.2

Two Halogens, a Nitrogen, and a Metalloid Function

Me3SiCl was able to trap intermediate 125 followed by the exchange of fluoride for triflate as counterion providing water-soluble 1-(difluorotrimethylsilylmethyl)-4-dimethylaminopyridinium triflate 136. The latter was reacted with benzaldehyde to give pyridinium triflate 137 (Scheme 25). The imidazol-N-difluoromethyl anion 129 and 2-methyl-1-difluoromethylbenziimidazole anion 141 were generated using (Et2N)3P in CH2Cl2 at 70 C under Marchenko–Ruppert reaction conditions from 127 and 1-difluoromethyl-2-methylbenzimidazole 140, and then trapped by Me3SiCl to yield imidazol-1-yltrimethylsilane 138 and benzimidazol-1-yltrimethylsilane 142 derivatives. Compounds 138 and 142 were also produced from 127 and 140 by the Grobe method, that is, using Al powder in N-methylpyrrolidinone (NMP) at 2040 C to generate the anions 129 and 141 followed by trapping with Me3SiCl. The heteroaryl-N-difluoromethyltrimethylsilanes 138 and 142 were quantitatively converted into their respective heteroarylium derivatives 139 and 143 (Scheme 26) <2001JFC(109)173, 2001SL374>.

+

i. Me3SiCl 125

ii. Me3SiOTf

+

NCF2SiMe3

Me2N

PhCHO +

Me4NF–

–OTf

+

Me2N F–

O– NMe4 NCF2C Ph H 137

136

Scheme 25

290

Functions Containing Two Halogens and Two Other Heteroatom Substituents N

(Et2N)3P, CH2Cl2, –70 °C

N R N CF2Br

R N CF2

or Al, NMP, 20–40 °C R = H or Ph

129

127

+

N

Me3SiCl

R N CF2SiMe3

MeOTf pentane

Me N CF2Br

–OTf

R N CF2SiMe3

138

N

Me

N

139

(Et2N)3P, CH2Cl2, –70 °C

N Me

or Al, NMP, 20 – 40 °C

N CF2

140

141

N

Me3SiCl

Me N CF2SiMe3

Me N+ –OTf Me N CF2SiMe3

MeOTf Pentane

142

143

Scheme 26

6.08.6

TWO HALOGENS AND TWO METALLOID FUNCTIONS

6.08.6.1 6.08.6.1.1

Two Halogens and Two Silicon Functions Linear carbosilanes

Perchloro-1,3-disilapropane Cl2C(SiCl3)2, prepared by photochlorination of Cl3SiCH2SiCl3, was converted into Cl2C(SiF3)2, reduced to Cl2C(SiH3)2, and transformed into Cl2C(SiCl3) (SiMeCl2). Several other compounds in this category, for example, Cl2C(TMS)2, Cl2C(TMS) (SiMe2Cl), Cl2C(TMS) (SiMeCl2), Cl2Si(CCl2SiCl3)2, Cl2Si(CCl2SiF3)2, Cl2C(SiCl3) (SiMeCl2), F3SiCCl2SiF2CH2SiF3, and F3SiCCl2SiF2CHClSiF3, have been prepared by various methods. Dihalo and dimethoxycarbosilanes of the general formula (XMe2Si)2 reacted with difluorocarbene to give difluoromethylsilane derivatives F2C(SiMe2X)2. Further reactions of F2C(SiMe2F)2 with Grignard and organolithium compounds have been reported <1995COFGT(6)249>. Reaction of 1,1,1,2,2-pentamethyl-2-chloromethyldisilane 144 with AlCl3 in pentane led to the rearrangement product 145 in 65% yield (Equation (36)) <1996IZV1511>. The dibromide, Br2C(SiMe3)2, was prepared on a multigram scale and in near quantitative yield by the addition of methylene dibromide to lithium diisopropylamide in the presence of Me3SiCl at 110 C. The use of excess Me3SiCl may prevent decomposition of the presumed intermediate carbenoids [LiCHBr2 and BrLiC(SiMe3)2] before silylation and/or prevent CC formation between BrLiC(SiMe3)2 and Br2C(SiMe3)2. Compound 145 was used in the chromium(II)-mediated transformation of a variety of aldehydes into vinylbis(silanes), RCH¼(SiMe3)2 <1997JCS(P1)2279>. Me Me3Si Si CCl3 Me 144

AlCl3, pentane 65%

Me3Si

Cl Me C Si Cl Cl Me

145

ð36Þ

291

Functions Containing Two Halogens and Two Other Heteroatom Substituents

Electroreduction of a mixture of ClF2C(SiMe3)2 and Me3SiCl in the THF/hexamethylphosphoramide (HMPA) solvent system and in the presence of Bu4NBr as an electrolyte support, resulted in the formation of Me3SiCF2SiMe3 148 (anion-derived product), as major product, and Me3SiCF2CF2SiMe3 147 (radical-derived product), as minor product. Compound 148 difluoro2 methylates aldehydes through the action of a difluoromethylene dianion, CF3 , equivalent <1997JA1572>. Difluoromethylbis(phenyl sulfone) 146, obtained by the oxidation of PhSO2CF2SPh with H2O2, and sulfone 74 reacts with Mg and TMSCl in DMF to produce 147 as the major product together with 148 as the minor product (Equation (37)) <2003JOC4457>. 25% 74

70%

Mg, TMSiCl

Me3SiCF2CF2SiMe3

DMF (PhSO2)2CF2

F

SiMe3

F

SiMe3 8%

+

79% 147

146

ð37Þ

148

Methylene dibromide reacts with lithium aluminum hydride (LDA) in THF at 78 C and then with diphenylmethylsilyl chloride 150 gave, via the lithium salt 149, the dibromosilylmethane 151. The latter was deprotonated by LDA under the same conditions and the resulting lithium salt 152 was silylated with Me3SiCl to yield the dibromodisilylmethane 153 (Scheme 27). By a similar type of reaction, CB4 and silyl chloride 150 reacted in the presence of 2 equiv. of n-BuLi to yield Br2C(SiMePh2)2 in 75% yield <2001CL956>.

Br

H

LDA, THF

Br

Br

H

–78 °C

Br

–Li+

Ph2MeSiCl 150

Br

SiMePh2

85%

Br

H

H

151

149

LDA, THF

SiMePh2

Br

–78 °C

Me3SiCl

–Li+

Br

Br

SiMePh2

Br

SiMe3 153

152

Scheme 27

6.08.6.1.2

Cyclic carbosilanes

In this category, representative compounds are five-membered rings 1,1,2,2,3,3,4,4,5,5decachloro[1,3]disilolane and 1,1,2,2,3,3,4-heptachloro-5-trimethylsilanyl-2,3-dihydro-1H-[1,3]disilole and the six-membered ring 1,1,2,2,3,3,4,4,5,5,6,6-dodecachloro[1,3,5]trisilinane. Several derivatives of these compounds have been synthesized and their chemistry explored <1995COFGT(6)249>. Photobromination of trisilacyclohexane 154 with NBS in CCl4 led to the formation of a mixture containing trisilacyclohexanes 155 and 156 in a ratio of 1:1 and about 10% of compound 157. Isolation of 155 and further photobromination afforded 156 in 90% yield (Scheme 28). Compound 157 was obtained in 70% yield by reacting 155 with ICl and treating the intermediate 158 with LiCBr3 (Scheme 29) <2000CJC1388>. Me

Me

Me Si Me

Si Me Me 154

Me

O

Si +

N Br O

CCl4 hν

Me

Me

Me Si Si Me Me Me Br Br 155

Scheme 28

Me Si

Si +

Br Br Si Me

Me Si Me Me Br Br 156

Me

CBr3 Si

+ Me Si Si Me Me Me Br Br 157

292

Functions Containing Two Halogens and Two Other Heteroatom Substituents Me

Cl Si

ICl 155

LiCBr3

Me Si Si Me Me Me Br Br

70%

157

158

Scheme 29

6.08.7

TWO HALOGENS AND TWO METAL FUNCTIONS

Several compounds in this category are represented by the general formula X2C(SnR3)2 and are prepared by the insertion of dichlorocarbene into tin derivatives R3Sn–SnR3. However, compound Br2C(SnMe3)2 could also be prepared by coupling of Me3SnCBr2TMS with Me3SnCBr2MgCl <1995COFGT(6)249>. The reaction of Na2[Fe2(CO)8] with Br2CF2 in pentane generates (CO)3Fe(-CO)2(CF2)Fe(CO)3 159. Compound 159 reacts with PPh3 with replacement of two CO ligands to form Fe2(CO)6(-CF2)(PPh3)2 160. Both complexes 159 and 160 were characterized by single crystal X-ray diffraction. A simplified structure of 159 and 160 extracted from the molecular structure is depicted below <2001ZAAC(627)1859>. O C F OC CO OC Fe C Fe CO CO OC F C O

F F PPh3 OC OC Fe Fe CO CO OC PPh CO 3 160

159

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294

Functions Containing Two Halogens and Two Other Heteroatom Substituents Biographical sketch

George Varvounis was born in Alexandria, Egypt, in 1953. He received his B.Sc. degree in chemistry and biochemistry in 1977 at the Polytechnic of Central London, UK, his M.Sc. degree in applied heterocyclic chemistry in 1979 and Ph.D. degree in organic chemistry in 1982 at the University of Salford, UK. He became a Lecturer at the University of Ioannina, Greece in 1982, an Assistant Professor in 1990, and an Associate Professor in 2001. He spent several short periods on sabbatical leave working with Dr. G. W. H. Cheeseman at Queen Elizabeth College, University of London in 1983–1987, with Professor H. Suschitzky and Dr. B. J. Wakefield at the University of Salford, and, with Professor J. A. S. Smith and Dr. C. W. Bird at King’s College London, University of London in 1988–1994. His research interests include the synthesis and properties of heterocyclic compounds, especially benzo- and naphtho-fused tricycles containing nitrogen, nitrogen and oxygen, or nitrogen and sulfur.

Nikolaos Karousis was born in Athens, Greece, in 1971. He received his B.Sc. degree in chemistry in 1995 and his Ph.D. degree in organic chemistry in 2003 under the supervision of Associate Professor Varvounis. During the period 2000–2002 he served in the Greek army. He is now working as postdoctoral fellow on the synthesis of analogs of the pyrrolo[2,1-c][1,4]benzodiazepine group of antitumor antibiotics.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 271–294

6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents S. V. YARLAGADDA and R. MURUGAN Reilly Industries Inc., Indianapolis, IN, USA 6.09.1 INTRODUCTION 6.09.2 ONE HALOGEN AND THREE CHALCOGENS 6.09.2.1 One Halogen and Three Oxygen Functions 6.09.2.2 One Halogen, Sulfur, and Oxygen Function 6.09.2.2.1 One halogen and three sulfur functions 6.09.2.2.2 One halogen, two sulfurs, and one oxygen function 6.09.2.3 One Halogen, Selenium, and Sulfur Function 6.09.3 ONE HALOGEN AND TWO CHALCOGENS 6.09.3.1 One Halogen, Two Chalcogens, and a Nitrogen 6.09.3.2 One Halogen, Two Sulfurs, and a Phosphorus Function 6.09.3.3 One Halogen, Two Sulfurs, and a Metal Function 6.09.4 ONE HALOGEN AND ONE CHALCOGEN 6.09.4.1 One Halogen, One Chalcogen, and Two Group 15 Elements 6.09.4.1.1 One halogen, one oxygen, and two nitrogen functions 6.09.4.1.2 One halogen, one sulfur, and two nitrogen functions 6.09.4.1.3 One halogen, one chalcogen, and two phosphorus functions 6.09.4.2 One Halogen, One Sulfur, and Two Silicon Functions 6.09.5 ONE HALOGEN AND THREE GROUP 15 ELEMENTS 6.09.5.1 One Halogen and Three Nitrogen Functions 6.09.5.1.1 Halonitromethanes 6.09.5.1.2 Miscellaneous halonitromethanes 6.09.5.1.3 Halotriaminomethanes 6.09.5.1.4 (Difluoroamino)fluorodiazirine 6.09.5.1.5 Fluorine-containing diaziridines 6.09.5.2 One Halogen, One Nitrogen, and Two Phosphorus Functions 6.09.5.3 One Halogen and Three Phosphorus Functions 6.09.6 ONE HALOGEN AND TWO GROUP 15 ELEMENTS 6.09.6.1 Metal Halodinitromethides 6.09.6.2 Metal Bis(phosphonyl) Halomethides 6.09.7 ONE HALOGEN AND ONE GROUP 15 ELEMENT 6.09.8 ONE HALOGEN AND METALLOID FUNCTION (THREE, TWO, OR ONE, TOGETHER WITH METALS) 6.09.8.1 One Halogen and Three Metalloid Functions 6.09.8.1.1 Three silicon functions 6.09.8.1.2 Two silicons and a germanium function 6.09.8.1.3 Two silicons and a boron function 6.09.8.1.4 Three boron functions or two borons and a metal function 6.09.8.2 One Halogen, Two Metalloids, and One Metal Function

295

296 296 296 296 296 298 298 298 298 298 299 299 299 299 299 300 300 300 300 300 300 301 301 301 301 301 302 302 302 302 302 302 302 303 303 303 303

296 6.09.1

Functions Containing One Halogen and Three Other Heteroatom Substituents INTRODUCTION

The literature search done for this chapter showed that little work has been done in this area. Many subsections of the corresponding chapter in COFGT (1995) <1995COFGT(6)271> had no relevant work done during the period 1993–2003 as shown by a literature search and confirmed by a search of authors, whose groups were researching in this area. Where no literature was found, a summary of the work reported in the corresponding sections of COFGT (1995) <1995COFGT(6)271> is provided. In addition, we have included a summary for a better comparison of the functional group transformations. Chalcogens is a term used for group 16 elements or the oxygen family.

6.09.2

ONE HALOGEN AND THREE CHALCOGENS

6.09.2.1

One Halogen and Three Oxygen Functions

These functional groups are called halo orthoformates. In COFGT (1995) <1995COFGT(6)271>, halo orthoformates were made by halogenation of orthoformates or carbonates, and by displacement by substituted oxygen nucleophilies on carbon tetrachloride. Halogen exchange on a halo orthoformate has also been used in preparing such compounds. Huang and DesMarteau have reported an interesting work on fluorination and reactions of a few fluoro compounds to give the fluoro orthoformates <2001JFC363, 1999CC1671>. The reaction of bis(fluoroformyl) peroxide with fluorine in the presence of cesium fluoride or potassium fluoride produces FOCF2OOC(O)F in 60% yield along with a small amount of FOCF2OOCF2OF. The hydrolysis of difluorofluoroxymethyl fluoroperformate gave FOCF2OOC(O)OOCF2OF, which on fluorination gave the corresponding fluoro orthoformate (Equation (1)). O O FOF2C

6.09.2.2 6.09.2.2.1

O O

O

CF2OF

F2

O FOF2C

F O

OF O O

ð1Þ CF2OF

One Halogen, Sulfur, and Oxygen Function One halogen and three sulfur functions

The approaches to halo thioorthoformate derivatives are very similar to those used for the corresponding oxygen compounds, halo orthoformates as shown in COFGT (1995) <1995COFGT(6)271>. However, sulfur can show more than two valencies and this leads to different types of halo thioorthoformates. Halo thioorthoformates can be acyclic or cyclic and the sulfur can be in sulfide, sulfoxide, or sulfone oxidation states. Halogenation of thiocarbonates either with halogens or with sulfenyl halides leads to halo thioorthoformates. Halogen exchange can also convert one halo thioorthoformate into another halo thioorthoformate. During the decade 1993–2003, little work was reported in this category. Senning and co-workers described the reactions of sulfenyl chlorides, in particular, chloro[(4-methylphenyl)sulfonyl] (phenylthio)-methanesulfenyl chloride 1, and chloro[(4-chlorophenyl)sulfonyl] [(1-methylethyl)thio]methanesulfenyl chloride 2 <1998SUL19, 1999SUL73, 1994PS(86)239> with thiobenzoic acid, 4-amino-ethylbenzene, and aniline. Compound 1 is dehalogenated by potassium iodide to a trithiocarbonate derivative (Equation (2)).

PhS

O ClS C S Cl O Me 1

Functions Containing One Halogen and Three Other Heteroatom Substituents

297

O SPr-i S C SCl O Cl Cl 2 Ph S O ClS C S Cl O

S O PhS C S O

KI, MeCN

ð2Þ

Me

Me

1

Tris(perfluoroorganochalcogenyl)methyl compounds are useful starting materials in organic chemistry. Thus (F3CS)3CCN easily undergoes hydrolysis in the presence of H2SO4 to the corresponding amide and reacts with oxalyl chloride to give the tris(trifluoromethylthio)methyl isocyanate. A number of methods are available for the synthesis of (F3CS)3CCN, however, the nucleophilic substitution of bromide in (CF3S)3CBr with silver cyanide is the most simple and convenient of them all (Equation (3)) <1994CB449>. AgCN (CF3S)3CCN

(CF3S)3CBr

ð3Þ

Tris(trifluoromethylselenyl or sulfuryl)carbenium, (CF3Z)3C+, (Z = Se or S) moieties are suitable synthons for the preparation of (CF3Z)3C halides <1996CB1383>. The carbenium ions prepared by the reaction of (CF3Se)3CF with arsenic pentafluoride in liquid SO2 medium on treatment with potassium halides provide (CF3Se)CX, (X = F, Cl, Br). The same approach is not extendable to the iodo analog as it gives the diseleno derivative and other olefinic compounds. Arsenic pentafluoride oxidizes tetra(trifluoromethylthio)methane, (F3CS)4C, to yield a stable salt, (F3CS)3C+ AsF6. This salt reacts with halide ions to form halo tris(trifluoromethylthio)methane, (F3CS)3CX (X = F, Cl, Br) as mentioned above for the equivalent selenium compound. In the case of iodide, it is oxidized to iodine with the formation of (F3CS)3CC(SCF3)3 <1994CB597, 1996JFC7>. Tris(trifluoromethylthio)carbonium arsenic hexafluoride, (F3CS)3C+ AsF6, easily abstracts a fluorine from 2,2,4-trifluoro-4-(trifluoromethylthio)1,3-dithietane to give (F3CS)3CF and 2,2-difluoro-4-(trifluoromethylthio)-1,3-dithietane hexafluoroarsenate (Equation (4)). F F S

F

F

(F3CS)3C+ AsF 6–

S

F3CS SCF3 + F3CS

SCF3 F

F

S S + SCF3 AsF6–

ð4Þ

Cyclic diaryliodonium salts fall under this category of halo thioorthoformate where all three sulfurs are in the sulfone form. These compounds showed generally poor reactivity towards nucleophilic substitution reactions. This surprisingly poor reactivity of cyclic diaryliodonium salts with nucleophiles was solved, shedding light on its mechanism <2000CSR315>. Bozopoulos and co-workers have determined the crystal structure of 2,20 -biphenyleneiodonium (methylsulfonyl) bis(phenylsulfonyl) methylide 3 <1994MI528>. The crystal structure of 3 showed that the two iodine carbon bonds and the two iodine oxygen secondary bonds to different sulfonyl groups, form a distorted planar tetragonal co-ordination around the iodine atom. Another feature of interest is the delocalization occurring in the carbanion and its planarity. O O S Me O O Ph S C S Ph O I O

3

298

Functions Containing One Halogen and Three Other Heteroatom Substituents

El-Sayed and co-workers have studied the effect of reaction conditions on the chlorotropic rearrangement of (1-adamantylsulfonyl) (pentachlorophenylthio)chloromethanesulfenyl chloride <1994JCS(P1)1251> (Scheme 1). The starting sulfenyl chloride gives (1-admantylsulfonyl)dichloromethyl pentachlorophenyl disulfide if left in CHCl3 for a few days, whereas it forms S-[(pentachlorophenylthio) dichloromethyl] adamantane-1-thiosulfonate when refluxed in ether or left standing in CHCl3 for a much longer time. O O S

R1

CHCl3, 5 days rt

Cl C

O O S

S S Cl R2

R1 Cl C

Cl

96%

CHCl3 Ether

S S R2

longer time rt

Reflux Cl

Cl

O O S S S 1 R 2 R C

R1 = 1-Ad R2 = C6Cl5

98%

Scheme 1

6.09.2.2.2

One halogen, two sulfurs, and one oxygen function

Halo dithioorthoformates have been obtained by the halogenation of dithiocarbonates <1995COFGT(6)271>. No new reports on the preparation of these halo dithioorthoformates for the review period 1993–2003 were found.

6.09.2.3

One Halogen, Selenium, and Sulfur Function

Halo selenothioorthoformates have been obtained by halogenation of diselenothiocarbonate and by the reaction of either selenyl or sulfenyl chloride with selenothiocarbonates <1995COFGT(6)271>. No new synthetic approach has been reported during the period 1993–2003 on this class of halo selenothioorthoformates.

6.09.3 6.09.3.1

ONE HALOGEN AND TWO CHALCOGENS One Halogen, Two Chalcogens, and a Nitrogen

These compounds, referred to as substituted halomethane derivatives, in COFGT (1995) <1995COFGT(6)271> are made by the addition of peroxides to cyanogen chloride, and by either addition of diazonium salts, or adding a nitration mixture to halo diarylsulfonylmethanes. The nitrogen part of this functional group can also be an azide. Crawford and co-workers have synthesized the interpseudohalogen, ClCS2N3, by chlorination of cyclic pseudohalogen (CS2N3)2 (Equation (5)) <1999ICA68>. S S C C S S N3 N 3

6.09.3.2

Cl2

Cl

ð5Þ

S S

N3

One Halogen, Two Sulfurs, and a Phosphorus Function

No new preparative methods were reported under this category in the decade 1993–2003. In COFGT (1995) <1995COFGT(6)271>, the synthesis of halodisulfonylmethyl phosphonates by halogenation of phosphonium salts, like triethoxyphosphonium bis(diphenylsulfonyl)methylide, was described. These phosphonates have also been prepared by nucleophilic displacement with a sulfur nucleophile on trihalomethylphosphonate ester.

Functions Containing One Halogen and Three Other Heteroatom Substituents 6.09.3.3

299

One Halogen, Two Sulfurs, and a Metal Function

No new preparative methods for this class of compounds have appeared in the period after 1999–2003 The metallo halo disulfonylmethanes reported in COFGT (1995) <1995COFGT(6)271> were prepared from bis(sulfonyl)halomethanes by treatment with either sodium hydroxide or by other strong bases like alkyllithiums.

6.09.4

ONE HALOGEN AND ONE CHALCOGEN

6.09.4.1

One Halogen, One Chalcogen, and Two Group 15 Elements

No preparations have been reported in the period 1993–2003 for this class of compounds, where the two group 15 elements are phosphorus and the chalcogen is sulfur.

6.09.4.1.1

One halogen, one oxygen, and two nitrogen functions

The most cited compounds in this category are oxaziridines. In general, the oxaziridines are prepared by the oxidation of perfluoroimines with aromatic peroxides or hydrogen peroxide. The reaction of polynitrohalomethane with t-butyl-1-adamantane carboxylate gave an oxaziridine derivative (Equation (6)) <1994ZOR704>. O

X O2N O2N NO2

+

X

37–39%

t-BuO

O N O

O2N

ð6Þ

X = -F -Cl

Moss and co-workers have reported the improved synthesis of alkoxychlorodiazirines <2002JPC12280> by a procedure similar to one reported by Smith and Stevens mentioned in COFGT (1995) (Scheme 2) <1995COFGT(6)271>. A mixture of octanol, cyanamide, and anhydrous trifluoromethanesulfonic acid was heated in chloroform under nitrogen, to give octyloxyisouronium trifluoromethane sulfonate (Step 1). This was then treated with LiCl in dimethyl sulfoxide and pentane as solvent, and subsequently with sodium hypochlorite to give the octyloxychlorodiazirine (Step 2).

Cyanamide HO-(CH2)7-Me

CF3SO3H

NH H2N C O (CH2)7 Me

. CF3SO3H

Step 1 LiCl, DMSO, pentane Step 2

NaOCl

N Cl N O (CH2)7 Me

Scheme 2

6.09.4.1.2

One halogen, one sulfur, and two nitrogen functions

No synthetic method has been reported in the decade 1993–2003 for this class of compounds. Compounds reported so far in this class are either 1-chloro-1,1-dinitromethyl sulfides or sulfones. They have been prepared by chlorination of the potassium salts of dinitromethyl sulfides or dinitromethyl sulfones <1995COFGT(6)271>.

300

Functions Containing One Halogen and Three Other Heteroatom Substituents

6.09.4.1.3

One halogen, one chalcogen, and two phosphorus functions

This class of compounds has been made by the Michaelis-Arbuzov reaction, between triethylphosphite and trichloromethyl phenyl ether <1995COFGT(6)271>. Halogenation of alkoxymethylene (or alkylthiomethylene) bisphosphonates also leads to this class of compounds <1995COFGT(6)271>. No new reports were found in the period 1993–2003.

6.09.4.2

One Halogen, One Sulfur, and Two Silicon Functions

There have not been any reports of the synthesis of this class of compounds in the period 1993–2003. Some examples were made previously by halogenation of bis(trimethylsilyl)methyl sulfides as reported in COFGT (1995) <1995COFGT(6)271>.

6.09.5

ONE HALOGEN AND THREE GROUP 15 ELEMENTS

6.09.5.1 6.09.5.1.1

One Halogen and Three Nitrogen Functions Halonitromethanes

Halonitromethanes (one halogen and three nitro groups) are widely used as oxidants in monopropellant fuels and in bipropellant systems with hypergolic fuels and their synthesis has been thoroughly covered in COFGT (1995) <1995COFGT(6)271>. The simplest synthetic route for halonitromethanes is the halogenation of trinitromethane potassium salt <1994ZOR704>. Fluoro--azidodinitromethane was prepared (Equation (7)) by reacting -(difluroamino)trinitromethane with sodium azide (NaN3) in the presence of dimethylformamide (DMF) and CH2Cl2 to give 37% yield of the desired product <1997MI324>. NO2 O2N C O N NF2

F O2N C O2N N3

NaN3, DMF, CH 2Cl 2 37%

2

ð7Þ

Reaction of difluoroaminotrinitromethane with metal fluorides (KF and CsF) in DMF yields a fluorodifluoroaminodinitromethane (Scheme 3). The reaction of F2NC(NO3)3 with LiBr in ethanol or DMF affords Br(O2N)C = NF rather than the expected bromo derivative, BrF2NC(NO2)2 <2001MI736>. F

NF2 O 2N O2N

i

NO2 ii

O2N O2N

NO2

ii Br

Br(O2N)C=NF i. KF, CsF, DMF ii. LiBr, DMF

O2N O2N

NF2

Scheme 3

6.09.5.1.2

Miscellaneous halonitromethanes

Halo compounds with two nitro groups and one amino group are reported under this category. The preparation of these compounds is thoroughly covered in COFGT (1995) <1995COFGT(6)271>. Compound, FC(NO2)2NF2 behaves similarly to FC(NO2)3, with respect to stability and decomposition. The Arrhenius parameters were determined for the decomposition rates controlled by rupture of a CNO2 bond in both the gaseous and the liquid states <1995IZV649, 2000MI234>.

Functions Containing One Halogen and Three Other Heteroatom Substituents 6.09.5.1.3

301

Halotriaminomethanes

Poly(fluoroamino)halomethanes come under this category and are used as bleaching and pyrotechnic agents. Several patents were known on these compounds, however, in the early 2000s only a few reports were available in academic journals <1995COFGT(6)271>.

6.09.5.1.4

(Difluoroamino)fluorodiazirine

No new reports have been available for the preparation of this class of compounds in the review period 1993–2003. This compound was reported in COFGT (1995) <1995COFGT(6)271>.

6.09.5.1.5

Fluorine-containing diaziridines

These compounds have been reported in COFGT (1995) <1995COFGT(6)271> to be made either by rearrangement of fluorinated guanidines or by reductive defluorination cyclization sequence as discussed earlier for (difluoroamino)-fluorodiazirine. No new reports were found for the preparation of these fluorine-containing diaziridines in the decade 1993–2003.

6.09.5.2

One Halogen, One Nitrogen, and Two Phosphorus Functions

No new reports have been available in the period 1993–2003 for the preparation of these compounds. Compounds in this class of this with two phophoryl groups and the nitrogen in the form of either an isocyanato group or an ammonium group were reported in COFGT (1995) <1995COFGT(6)271>. The halo diphosphonylmethyl isocyanate compounds have been made by double nucleophilic displacement with trialkylphosphites on trichloromethyl isocyanate. The corresponding ammonium compound has been made by chlorination of diphosphonylmethyl trimethyl ammonium salt.

6.09.5.3

One Halogen and Three Phosphorus Functions

Blackburn and co-workers <1998CC2619, 1999PS(144)541> described the preparation of halogenated methanetriyl trisphosphonic acids and their esters for incorporation into analogs of adenosine 50 -triphosphate <1999AG(E)1244>. They envisaged that multiplicity of anionic charge is a major factor in protein affinity. Tetraisopropyl methylenebisphosphonate was reacted with diethyl chlorophosphite in the presence of NaHMDS (sodium hexamethyl disilazane), followed by oxidation with iodine to give methanetriyl trisphosphonic ester (Scheme 4). The resultant ester was treated with NaOCl to give chloromethane trisphosphonate ester, treatment with FClO3 gives the fluoro derivative (Scheme 5). Both the haloesters are hydrolyzed by trimethylsilyl bromide and Bu3N to afford the corresponding halo-substituted acids, which are good in ligation of calcium ion and useful as potential bone affinity agents.

OPri PriO P P i Pr O i O O OPr

i

EtO

P

O

OEt

PriO OPri P P i Pr O i O O OPr i: NaHMDS, (EtO)2PCl, toluene.

Scheme 4

ii

OEt P OEt

OPri PriO P P PriO i O O OPr ii: 0.5 M I2 solution in Py-THF-H2O

302

Functions Containing One Halogen and Three Other Heteroatom Substituents

O

OEt P OEt

PriO OPri P P i Pr O i O O OPr

i

OEt O P OEt Cl PriO OPri P P PriO i O O OPr

O

iii

F

ii

OEt P OEt

OPri PriO P P i Pr O i O O OPr

OH O O– Cl P HO OH P –O P – O O O

OH P O– OH HO P –O P – O O O O

ii

F

i. 20%NaOCl, NaHCO3, 0 °C, 1.5 h ii. TMSBr, Bu3N, CH2Cl2, reflux, overnight iii. FClO3, NaHMDS, THF, -75 °C

Scheme 5

6.09.6

ONE HALOGEN AND TWO GROUP 15 ELEMENTS

6.09.6.1

Metal Halodinitromethides

New preparations of this class of compounds have not been reported for the period 1993–2003. Carbanions have been made from halodinitromethanes and halotrinitromethane with metals such as potassium, silver, and mercury <1995COFGT(6)271>.

6.09.6.2

Metal Bis(phosphonyl) Halomethides

Alkali metal salts of alkylidenebis(phosphonic acid) or esters have been widely used in laundry detergents, and have some biological applications. Little progress has been made in the decade, 1993–2003, on these compounds since they were covered fully in COFGT (1995) <1995COFGT(6)271>. They are usually made from the dichloromethylene bis(phosphonic acid) ester and either a metal base or an amino base <2001WOP0121629, 1999WOP9920634>.

6.09.7

ONE HALOGEN AND ONE GROUP 15 ELEMENT

Compounds of this class were well documented in COFGT (1995) <1995COFGT(6)271>. During the decade 1993–2003 no reports were found in the literature for this class of compounds.

6.09.8

ONE HALOGEN AND METALLOID FUNCTION (THREE, TWO, OR ONE, TOGETHER WITH METALS)

6.09.8.1 6.09.8.1.1

One Halogen and Three Metalloid Functions Three silicon functions

This class of compounds, organosilanes was thoroughly covered in COFGT (1995) <1995COFGT(6)271>. A widely used procedure is the halogenation of the corresponding active dialkylmagnesium compound. For instance, the reaction of I2 and Br2 with Mg(Tsi)2 (Tsi = (Me3Si)3C) gives TsiI and TsiBr, respectively. Mg(Tsi)2 was obtained by heating the lithium magnesate [Li(THF)2(-Br)2Mg(Tsi) (THF)] in vacuum. Whereas, the TsiCl was prepared by reacting the dialkylmagnesium with benzenesulfonyl chloride (Scheme 6) <1994JOM(480)199>.

Functions Containing One Halogen and Three Other Heteroatom Substituents PhSO2Cl Mg(Tsi)2

303

Tsi Cl

Br2 Tsi Br

I2

TMS Tsi = C TMS TMS

Tsi I

Scheme 6

Halo tris(substituted dimethylsilyl)methane reacts with magnesium metal to form the Grignard reagent. Interestingly, the reaction of iodotris(dimethylamino-dimethylsilyl)methane with magnesium gives the planar carbanionic center 4, without the C–Mg covalent bond <1997OM503>.

C Me2Si

SiMe2

Me2Si NMe2

Me2N

Mg

NMe2

I 4

6.09.8.1.2

Two silicons and a germanium function

No publication was found under this category in the review period 1993–2003. These compounds have been reported in COFGT (1995) <1995COFGT(6)271> to be made from dihalo di(trimethylsilyl)methane and organo germanium halide with butyl lithium as the coupling agent.

6.09.8.1.3

Two silicons and a boron function

The only compound reported in COFGT (1995) was bromo[bromobis(isopropyl)aminoboryl]bis(trimethylsilyl)methane. This compound was made by the addition of bromine to the respective methylidene bis(isopropyl)aminoborane <1995COFGT(6)271>. No work was reported for this class of compounds in the decade 1993–2003.

6.09.8.1.4

Three boron functions or two borons and a metal function

There have not been any reports of the preparation of this class of compounds since COFGT (1995) <1995COFGT(6)271> was published. These compounds can be prepared from tetraborylmethanes by the following methods: tetraborylmethanes are converted into triborylmethides on treatment with alkyl lithiums, which on further halogenation leads to the expected final products. A similar approach was used to make the metal function containing class of compounds. Triborylmethyl halides on treatment with alkyl lithium followed by organometal halides leads to the expected products, diborylhaloorganometallomethanes.

6.09.8.2

One Halogen, Two Metalloids, and One Metal Function

No reports have been found for this class of compounds since the publication of COFGT (1995) <1995COFGT(6)271>. These compounds have been prepared from dihalobis(trimethylsilyl)methanes, which on reaction with alkyl lithium generates halobis(trimethylsilyl)methides. The lithium in these methides could be exchanged with other metals leading to the final products.

304

Functions Containing One Halogen and Three Other Heteroatom Substituents

REFERENCES 1994CB449 1994CB597 1994JCS(P1)1251 1994JOM(480)199 1994PS(86)239 1994MI528 1994ZOR704 1995COFGT(6)271 1995IZV649 1996CB1383 1996JFC7 1997OM503 1997MI324 1998CC2619 1998SUL19 1999AG(E)1244 1999CC1671 1999ICA68 1999PS(144)541 1999SUL73 1999WOP9920634 2000CSR315 2000MI234 2001JFC363 2001MI736 2001WOP0121629 2002JPC12280

R. Boese, A. Haas, M. Lieb, U. Roeske, Chem. Ber. 1994, 127, 449–455. R. Boese, A. Haas, C. Krueger, G. Moeller, A. Waterfeld, Chem. Ber. 1994, 127, 597–603. I. El-Sayed, V. K. Belsky, V. E. Zavodnik, K. A. Jorgensen, A. Senning, J. Chem. Soc., Perkin Trans. 1994, 1, 1251–1252. S. S. Al-Juaid, C. Eaborn, P. B. Hitchcock, K. Kundu, C. A. McGeary, J. D. Smith, J. Organomet. Chem. 1994, 480, 199–203. I. El-Sayed, M. F. Abdel-Megeed, S. M. Yassin, A. Senning, Phosporus Sulfur Silicon Relat. Elem. 1994, 86, 239–257. A. P. Bozopoulos, C. A. Kavounis, G. A. Stergioudis, P. J. Rentzeperis, A. Varvoglis, Z. Kristal. 1994, 209, 528–530. V. L. Medzhinski, E. L. Golod, Zh. Org. Khim. 1994, 30, 704–706. A. Marinetti, P. Savignac, Functions containing one hologen and three other heteroatom substituents, in Comprehensive Organic Functional Group Transformations, A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Eds., Elsevier, Oxford, 1995, Vol. 6, pp. 271–294. V. N. Grebennikov, G. M. Nazin, G. B. Manelis, Izv. Akad. Nauk SSSR, Ser. Khim. 1995, 4, 649–651. H. Alois, M. Guido, Chem. Ber. 1996, 129, 1383–1388. S. Munavalli, D. I. Rossman, D. K. Rohrbaugh, C. P. Ferguson, H. D. Durst, J. Fluorine Chem. 1996, 76, 7–13. C. Eaborn, A. Farook, P. B. Hitchcock, J. D. Smith, Organometallics 1997, 16, 503–504. G. Kh. Khisamutdinov, V. I. Slovetsky, Yu. M. Golub, S. A. Shevelev, A. A. Fainzil’berg, Russ. Chem. Bull. 1997, 46, 324–327. X. Liu, H. Adams, G. M. Blackburn, J. Chem. Soc., Chem. Commn. 1998, 2619–2620. F. A. G. El-Essawy, S. M. Yassin, I. A. El-Sakka, A. F. Khattab, I. Sotofte, J. O. Madsen, A. Senning, Sulfur Lett. 1998, 22, 19–32. L. Xiaohai, B. Charles, G. Andrzej, S. Elzbieta, G. M. Blackburn, Angew. Chem. Int. Ed. Engl. 1999, 389, 1244–1247. Q. Huang, D. D. DesMarteau, J. Chem. Soc., Chem. Commn. 1999, 17, 1671–1672. M. J. Crawford, T. M. Klapotke, Inorg. Chim. Acta 1999, 294, 68–72. X. Liu, X. R. Zhang, G. M. Blackburn, Phosphorus Sulfur Silicon Relat. Elem. 1999, 144, 541–544. F. A. G. El-Essawy, A. F. Khattab, S. M. Yassin, I. A. El-Sakka, J. O. Madsen, A. Senning, Sulfur Lett. 1999, 22, 73–84. E. Pohjala, J. Vepsalainen, H. Nupponen, J. Kahkonen, L. Lauren, R. Hannuniemi, T. Jarvinen, M. Ahlmark, PCT Int. Appl. WO (World Intellectual Property Organization Pat. Appl.) WO 99/ 20634. V. V. Grushin, Chem. Soc. Rev. 2000, 29, 315–324. G. M. Nazin, V. G. Prokudin, G. B. Manelis, Russ. Chem. Bull. 2000, 49, 234–237. Q. Huang, D. D. DesMarteau, J. Fluorine Chem. 2001, 112, 363–368. G. Kh. Khisamutdinov, S. A. Shevelev, Russ. Chem. Bull. 2001, 50, 736–737. M. Purdie, PCT Int. Appl. WO (World Intellectual Property Organization Pat.) WO 01/21629. R. A. Moss, Y. Ma, F. Zheng, R. R. Sauers, T. Bally, A. Maltsev, J. P. Toscano, B. M. Sharalter, J. Phys. Chem. 2002, 106, 12280–12291.

Functions Containing One Halogen and Three Other Heteroatom Substituents

305

Biographical sketch

Subbarao Yarlagadda received his M.Sc. in organic chemistry from Andhra University, Waltair, India. He obtained his Ph.D. in 1991 from the Indian Institute of Chemical Technology (IICT), Hyderabad, India. His doctoral work was chiefly on selective organic transformations by using a new class of heterogenised homogeneous catalysts. Later, he joined, as a postdoctoral fellow, Professor M. Graziani at the University of Trieste, Italy under the UNIDO program, and worked on polydentate ligands and their metal complexes for an oxidative amination reaction. From 1992 to 1996, he was a staff scientist in Dr. A.V. Ramarao’s group at IICT, India, and worked on the synthesis of fine and specialty chemicals, pharmaceutical intermediates by using zeolite catalysts. In 1996, he joined Professor P. A. Jacobs at the Catholic University of Louvain, Belgium and worked on mesoporous zeolites and homogeneous catalysts for the synthesis of specialty chemicals. Since July 1998, he has worked at Reilly Industries, Indianapolis, IN, USA as a Research Associate. His current interests include: the process development, invention of new routes for the existing products, synthesis of fine and specialty chemicals, development of new catalysts for the synthesis of pharmaceutical and agrochemical intermediates, and vitamins.

Ramiah Murugan: Born in Madurai, India, he obtained his B.Sc. in 1975 from American College and M.Sc. in 1977 from Madurai University. After four years of working as a Junior Scientist at Madurai University, he joined Professor A. R. Katritzky’s group at the University of Florida, USA and obtained his Ph.D. in 1987. He continued there for two more years doing postdoctoral work in the area of high temperature aqueous organic chemistry. He joined Reilly Industries Inc., Indianapolis, IN, USA in 1989 and is currently a Senior Research Associate. His research interests include: synthesis of intermediates for pharmaceuticals, agrochemical products, and performance products; mechanistic studies; catalysis; polymer chemistry; and process development.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 295–305

6.10 Functions Containing Four or Three Chalcogens (and No Halogens) A. SENNING and J. Ø. MADSEN Technical University of Denmark, Kgs. Lyngby, Denmark 6.10.1 TETRACHALCOGENOMETHANES 6.10.1.1 Four Similar Chalcogens 6.10.1.1.1 Four oxygen functions 6.10.1.1.2 Four sulfur functions 6.10.1.1.3 Four selenium functions 6.10.1.1.4 Four tellurium functions 6.10.1.2 Three Similar and One Different Chalcogen 6.10.1.2.1 Trioxygen-substituted methyl chalcogens 6.10.1.2.2 Trisulfur-substituted methyl chalcogens 6.10.1.2.3 Triselenium- or tritellurium-substituted methyl chalcogens 6.10.1.3 Two Similar and Two Different Chalcogens 6.10.1.3.1 Dioxygen-substituted methylene dichalcogens 6.10.1.3.2 Disulfur-substituted methylene dichalcogens 6.10.1.3.3 Diselenium- or ditellurium-substituted methylene dichalcogens 6.10.2 TRICHALCOGENOMETHANES 6.10.2.1 Methanes Bearing Three Oxygens and a Group 15 Element, Metalloid, or Metal Function 6.10.2.2 Methanes Bearing Three Sulfurs and a Group 15 Element, Metalloid, or Metal Function 6.10.2.3 Methanes Bearing Three Seleniums or Three Telluriums and a Group 15 Element, Metalloid, or Metal Function 6.10.2.4 Methanes Bearing Three Dissimilar Chalcogens and a Group 15 Element, Metalloid, or Metal Function

6.10.1

307 307 307 309 310 311 311 311 311 311 312 312 312 312 312 312 313 313 313

TETRACHALCOGENOMETHANES

6.10.1.1 6.10.1.1.1

Four Similar Chalcogens Four oxygen functions

The traditional approaches to ortho-carbonates (RO)4C using chloropicrin CCl3NO2, trichloroacetonitrile CCl3CN, cf. references <2002EUP1207147> and <2002GEP10121116>, trichloromethanesulfenyl chloride CCl3SCl, or N-(trichloromethyl)imidocarbonyl dichloride (CCl3)N¼CCl2 as C1 donor in ortho-carbonate syntheses have been supplemented by a procedure using CS2. Monovalent and divalent alcohols (or phenols) react with CS2 in the presence of stoichiometric amounts of CF3CO2Ag and excess Et3N to form ortho-carbonates (RO)4C in excellent yields (Equation (1)). Tetraethyl ortho-carbonate (EtO)4C is formed in 61% yield, tetraphenyl orthocarbonate (PhO)4C in 68% yield, and the spiro compounds 1–4 in 33%, 75%, 31%, and 20% yield, respectively <1998H(48)461>. 307

308

Functions Containing Four or Three Chalcogens CF3COOAg

CS2 + 4 ROH

Ph

O O

Ph

Ph

O O

Ph

NEt3

ð1Þ

C(OR)4

O O O O 2

1

O O

O O

O

O O

O

O O

3

4

Heating of O,O-bis(4-chlorophenyl)iminocarbonate (4-ClC6H4O)2C(¼NH) to 180 C gives a very low yield of tetrakis(4-chlorophenyl) ortho-carbonate (4-ClC6H4O)4C <1992JPR(334)95>. 2,2-Diphenoxy-1,3-dioxan has been prepared in 80% yield from 1,3-propanediol and dichlorodiphenoxymethane (PhO)2CCl2 <1999AJC657>. Dialkoxydichloromethanes react with alcohols in the presence of FeCl3 to yield the corresponding ortho-carbonater <1991IZV198>. Propylene carbonate 5 adds epichlorohydrin 6 in the presence of BF3 to form 2-(chloromethyl)8-methyl-1,4,6,9-tetraoxaspiro[4.4]nonane 7 as a mixture of stereoisomers (Scheme 1) which upon treatment with EtONa 7 forms the corresponding methylene derivative 8 <2002MI588>. A spirooligomer 9 is formed when pentaerythritol C(CH2OH)4 is treated with (EtO)4C at 260 C for 12 h <2002JA4942>. Other bis(hydroxymethyl) compounds form spirocyclic ortho-carbonates upon heating with (MeO)4C and acid <1992JAP04164085>. Spirocycli ortho-carbonates are also avialable from cyclic carbonates and oxiranes in the presence of 1-alkylpyridinium salts <1990CL2019>.

Me O

O

+

BF3.OEt2

Cl

Me

O O

O

O O

6

O 5

7 –HCl

Me

O O O O 8

Scheme 1

HO

O O

HO

O O n

9

O O

OH

O O

OH

Cl

309

Functions Containing Four or Three Chalcogens

Symmetrical tetrasilyl ortho-carbonates have been prepared by heating of alkene-1,1-disilanols, such as CH2¼C(SiMe2OH)2 and (MeO)4C, in the presence of p-toluenesulfonic acid <1992JAP04169592>. Chlorination of a solution of O,O-bis(2,2,2-trifluoroethyl)thiocarbonate (CF3CH2O)2C(¼S) and 2,2,2-trinitroethanol (O2N)3CCH2OH in 1,2-dichloroethane gives 90% yield of bis(2,2,2trinitroethyl) bis(2,2,2-trifluoroethyl) ortho-carbonate [(O2N)3CCH2O]2C(OCH2CF3)2 <1998USP5783732>. Divinyl-substituted ortho-carbonates can be converted to the corresponding diepoxides with MCPBA <1999JAP11158182>.

6.10.1.1.2

Four sulfur functions

Spiro compounds continue to dominate the portfolio of available tetrathio-ortho-carbonates (RS)4C. Dibenzo[3,4;10,11]-1,6,8,13-tetrathiaspiro[6.6]tridecane 10 has been prepared in quantitative yield by heating (MeS)4C (the synthesis of which was accomplished by a modified and somewhat improved Backer procedure involving N,N0 -dinitrosoisothioureas as key intermediates) and benzene-1,2-dimethanethiol 1,2-C6H4(CH2SH)2 with acid catalysis <1997MM6721>.

S

S

S

S

10

2-Methylenepropane-1,3-dithiol HSCH2C(¼CH2)CH2SH reacts with dichlorodiphenoxymethane (PhO)2CCl2 in the ratio 2:1 to form the tetrathio-ortho-carbonate 3,9-bis(methylene)1,5,7,11-tetrathiaspiro[5.5]undecane <1996AJC1261>. The tetrathio-ortho-carbonates 13a–13d have been prepared from the zinc complexes 11 and the trissulfanylcarbenium salts 12 as shown in Equation (2) <1999SM(102)1617>. 2– RS + 2NMe4

RS

S S

S S

S S Zn S S

RS

S

S

R1 +

S

S

+

S

RS

RS

–

SMe BF4

12

11

RS

S

S

S

S

S

S S

S

R1

ð2Þ

S

13 13a, R = Me, R1 = H 13b, R = R1 = Me 13c, R, R = CH2CH2; R1 = H 13d, R, R = CH2CH2; R1 = Me

Tetrakis(trifluoromethyl)tetrathio-ortho-carbonate (CF3S)4C has been obtained in 61% yield from CBr2Cl2 and (CF3)SCu <1996JFC(76)7>. Spirocyclic 1,4,6,9-tetrathiaspiro[4.4]nonanes are formed in very low yields (4–5%) when 1,3-dithiolan-2-ones are treated with thiiranes <1996JCS(P1)289>. A particularly neat high-yielding access to spirocyclic tetrathio-ortho-carbonates such as 16 has been found in the reaction between 2H-benzo[b]thiete 14 and cyclic trithiocarbonates such as 15 (cf. Equation (3)) <1997LA1603>.

310

Functions Containing Four or Three Chalcogens S

S

S

+

S

S

ð3Þ

S

S 15

14

S

16

The unexpectedly stable tetrathio-ortho-carbonate 18, i.e., 4,7-dichloro-2-isopropylsulfanyl-2sulfanyl-1,3-dithiolo[4,5-c]pyridine-6-carbonitrile, was obtained (22% yield) from the reaction between 3,4,5,6-tetrachloropyridine-2-carbonitrile 17 and potassium isopropyltrithiocarbonate (cf. Equation (4)) <1998MI297>. Cl Cl Cl

Cl N

HS Me2CHSC(=S)SK

S

SCHMe2 S Cl

EtO S +

SCHMe2 S Cl

EtOH

CN

Cl

N

CN

Cl

17

N

ð4Þ

CN

19

18

Following an established procedure, bis(methylsulfonyl)methane (MeSO2)2CH2 can be disulfenylated with N-(ethylsulfanyl)phthalimide 1,2-C6H4[C(¼O)]2NSEt to yield bis(ethylsulfanyl)bis(methylsulfonyl)methane (EtS)2C(SO2Me)2 <2002TL1377>. The unexpected unsymmetrical dimerization of the thiocarbonyl ylide 20, formed in situ from PhS(¼O)2C(¼S)SC6H4Cl-4 and Me3SiCHN2, leads to tetrathio-ortho-carbonate 21, cf. Equation (5) <2003EJO813>. Me3Si 4-ClC6H4S

CHSiMe3 4-ClC6H4S

C S PhSO2

SiMe3

+

– C S

S

ð5Þ

PhSO2

20

SO2Ph

4-ClC6H4S 21

6.10.1.1.3

Four selenium functions

Two new tetraseleno-ortho-carbonates (RSe)4C, both spiroheterocycles, have been reported. 2,3,7,8-Tetramethyl-1,4,6,9-tetraselenaspiro[5.5]nona-2,7-diene 22 is formed in low yield from 4,5-dimethyl-1,3-diselenole-2-selone, 4,5-methylenedithio-1,3-dithiol-2-one, and (MeO)3P <1994ZOR1009>. The structure of 22 was proven by X-ray crystallography <1995DOK(340)62>.

Me

Se Se

Me

Me

Se Se

Me

22

The reaction between the ring-strained alkyne cyclooctyne and CSe2 yields, among other products, 3.3% of the yellow 4,4,5,5,6,6,7,7,8,8,9,9-dodecahydro-2,20 -spirobi[cycloocta-1,3-diselenole] 25, the main products being the triselenocarbonate 23 and the tetraselanylethene 24 (cf. Equation (6)) <2000JOC8940>.

311

Functions Containing Four or Three Chalcogens Se Se

+ CSe2

+

Se 23

Se

Se

Se

Se

+

Se Se 25

24

6.10.1.1.4

ð6Þ

Se Se

Four tellurium functions

Tetratelluro-ortho-carbonates (RTe)4C are still unknown.

6.10.1.2

Three Similar and One Different Chalcogen

6.10.1.2.1

Trioxygen-substituted methyl chalcogens

Cyclic thio-ortho-carbonates (RO)3CSR have been prepared from dichlorodiphenoxymethane (PhO)2CCl2 and ,!-mercaptoalkanols <1999AJC657>. No seleno-ortho-carbonates (RO)3CSeR or telluro-ortho-carbonates (RO)3CTeR are on record.

6.10.1.2.2

Trisulfur-substituted methyl chalcogens

The trissulfanylcarbenium salt 26, when treated with NaBH4 in EtOH, gives a mixture of the trithio-ortho-carbonate 27 and the trithio-ortho-formate 28 (cf. Equation (7)) <2001MI145>. Me

Me

BF4–

+

S

NaBH4

SMe

EtO2C

EtO2C

S

SMe

SMe

EtO2C

S OEt

S

EtOH

S

S

Me S

27

26

S

S

ð7Þ

28

Good yields of 1-oxa-4,6,9-trithiaspiro[4.4]nonanes 31 are obtained from the appropriate 1,3-dithiolane-2-thiones 29 and oxiranes 30 (cf. Equation (8)) <1996JCS(P1)289>. 1

2

R

R

S

S S

R3

R4

+ O 30

HBF4.Et2O PhCl

R1 2

R

S

S

R3(R4)

S

O

R (R )

4

3

ð8Þ

31

29

The trithio-ortho-carbonate 19, i.e., 4,7-dichloro-2-ethoxy-2-isopropylsulfanyl-1,3-dithiolo[4,5-c]pyridine-6-carbonitrile, has been obtained according to Equation (4) <1998MI297>. Seleno-trithio-ortho-carbonates (RS)3CSeR and telluro-trithio-ortho-carbonates (RS)3CTeR are unknown.

6.10.1.2.3

Triselenium- or tritellurium-substituted methyl chalcogens

None of the hypothetical compound classes (RSe)3COR, (RSe)3CSR, (RSe)3CTeR, (RTe)3COR, (RTe)3CSR, or (RTe)3CSeR have been reported.

312

Functions Containing Four or Three Chalcogens

6.10.1.3

Two Similar and Two Different Chalcogens

6.10.1.3.1

Dioxygen-substituted methylene dichalcogens

A modest yield of 1,6-dioxa-4,9-dithiaspiro[4.4]nonane 32 has been obtained in the reaction between 2-mercaptoethanol and (PhO)2CCl2. The higher homolog 1,5-dioxa-7,11-dithiaspiro[5.5]undecane 33 can be made from 2,2-diphenoxy-1,3-dioxan and propane-1,3-dithiol (62% yield) or from 2,2-diphenoxy-1,3-dithian and propane-1,3-diol (37% yield). Either reactant may also carry a methylene substituent to give the corresponding methylene-substituted spiro-ortho esters <1999AJC657>.

O O

O S

S

O S

S 32

6.10.1.3.2

33

Disulfur-substituted methylene dichalcogens

No further advances have occurred in this area since the publication of chapter 6.10.1.3.2 in <1995COFGT(6)295>.

6.10.1.3.3

Diselenium- or ditellurium-substituted methylene dichalcogens

Treatment of dimethyl 2-selenoxo-1,3-thiaselenole-4,5-dicarboxylate 34 with Ph3P leads to a mixture of the (E )- and (Z )-diselenadithiafulvalenes 35 (cf. Equation (9)) <1980JOC2632>.

MeO2C

S Se

MeO2C

Ph3P

Se 34

ð9Þ MeO2C

Se

Se

CO2Me

MeO2C

S

Se

CO2Me

MeO2C

Se

S

CO2Me

+ MeO2C

S

S

CO2Me

(Z )-35

6.10.2 6.10.2.1

(E )-35

TRICHALCOGENOMETHANES Methanes Bearing Three Oxygens and a Group 15 Element, Metalloid, or Metal Function

3,4-Dihydro-2,2-dimethoxy-5,5-dimethyl-1,3,4-oxadiazole 38, useful as a source of dimethoxycarbene upon pyrolysis, has been prepared from acetone methoxycarbonylhydrazone 36 via the intermediate 37 as shown in Equation (10) <1994JA1161>. The analogous spiro compound 39 has been obtained along similar lines <2002CJC1187>.

313

Functions Containing Four or Three Chalcogens

Me Me

OMe NH C C N O

Me N N

LTA AcOH

O

Me

36

OMe OAc

37 Me N N

MeOH

Me

O

ð10Þ OMe OMe

38 LTA = Pb(MeCO2)4

Ph O

O

N O N Me Me 39

Tris(fluorosulfinyloxy)methyllithium [[FS(¼O)O]3C]Li has been prepared for use in lithium batteries <1996FRP2730988>.

6.10.2.2

Methanes Bearing Three Sulfurs and a Group 15 Element, Metalloid, or Metal Function

2,3-Dihydro-9a-(methylsulfanyl)-7-(trifluoromethoxy)thiazolo[2,3-b]benzothiazole 41 has been prepared in three simple steps from benzothiazole 40 (cf. Equation (11)) <1999JMC2828>. N

N Cl

S

CF3O 40

CF3O

S

S SMe

ð11Þ

41

Nitrotris[(trifluoromethyl)sulfanyl]methane (CF3S)3CNO2 is formed in 45% yield upon treatment of bis[tris[(trifluoromethyl)sulfanyl]methyl] disulfide (CF3S)3CSSC(SCF3)3 with NO2 <1994CB597>. Tris[(trifluoromethyl)sulfonyl]methyllithium [(CF3SO2)3C]Li has been prepared as starting material for the corresponding fluorine compound (CF3SO2)CF <2003GEP10258577>. The corresponding caesium salt [(CF3SO2)3C]Cs has also been prepared <1993WOP9309092>.

6.10.2.3

Methanes Bearing Three Seleniums or Three Telluriums and a Group 15 Element, Metalloid, or Metal Function

The salt [(CF3Se)3C][AsF6] is available, inter alia, from tetrakis(trifluoromethyl) tetraselenoortho-carbonate (CF3Se)4C and AsF5 <1996CB1383>.

6.10.2.4

Methanes Bearing Three Dissimilar Chalcogens and a Group 15 Element, Metalloid, or Metal Function

No further advances have occurred in this area since the publication of chapter 6.10.2.4 in <1995COFGT(6)295>.

314

Functions Containing Four or Three Chalcogens

REFERENCES 1980JOC2632 1990CL2019 1991IZV198 1992JAP04164085 1992JAP04169592 1992JPR(334)95 1993WOP9309092 1994CB597 1994JA1161 1994ZOR1009 1995COFGT(6)295 1995DOK(340)62 1996AJC1261 1996CB1383 1996FRP2730988 1996JCS(P1)289 1996JFC(76)7 1997LA1603 1997MM6721 1998H(48)461 1998MI297 1998USP5783732 1999AJC657 1999JAP11158182 1999JMC2828

1999SM(102)1617 2000JOC8940 2001MI145 2002CJC1187 2002EUP1207147 2002GEP10121116 2002JA4942 2002MI588 2002TL1377 2003EJO813 2003GEP10258577

M. V. Lakshmikantham, M. P. Cava, J. Org. Chem. 1980, 45, 2632–2636. S. B. Lee, T. Takata, T. Endo, Chem. Lett. 1990, 2019–2022. I. T. Eremenko, G. V. Oreshko, M. A. Fadeev, Izv. Akad. Nauk SSSR, Ser. Khim. 1991, 198–200. Higashiura, M.; Nishino, H.; Kodera Y., (Toyobo Co., Ltd., Japan), Jpn. Patent JP 04 164 085, 1992 (Chem. Abstr. 1992, 117, 191857). Nishino, H.; Higashiura, M.; Ohashi, H.; Kodera, Y, (Toyobo Co., Ltd., Japan), Jpn. Patent JP 04 169 592, 1992 (Chem. Abstr. 1993, 118, 7186). M. Bauer, D. Janietz, G. Reck, B. Schulz, J. Prakt. Chem.-Chem.-Ztg. 1992, 334, 95–97. Armand, M.; Benrabah, D.; Sanchez, J. Y., (Centre National de la Recherche Scientifique CNRS, France), PCT Int. Appl. WO 9 309 092, 1993 (Chem. Abstr., 1994, 120, 180111). R. Boese, A. Haas, C. Kru¨ger, G. Mo¨ller, A. Waterfeld, Chem. Ber. 1994, 127, 597–603. K. Kassam, D. L. Pole, M. El-Saidi, J. Warkentin, J. Am. Chem. Soc. 1994, 116, 1161–1162. M. L. Petrov, I. K. Rubtsova, Zh. Org. Khim. 1994, 30, 1009–1011. A. H. Gouliaev, A. Senning, Functions containing four or three chalcogens (and no halogens), in Comprehensive Organic Functional Group Transformations, A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Eds., Elsevier, Oxford, 1995, Vol. 6, pp. 295–318. Yu. E. Ovchinnikov, K. A. Potekhin, V. Panov, Yu. T. Struchkov, Dokl. Akad. Nauk 1995, 340, 62–66. M. K. Bromley, S. J. Gason, A. G. Jhingran, M. G. Looney, D. H. Solomon, Aust. J. Chem. 1996, 49, 1261–1262. A. Haas, G. Mo¨ller, Chem. Ber. 1996, 129, 1383–1388. Guyomard, D.; Piffard, Y.; Leroux, F.; Tournoux, M., (Centre National de la Recherche Scientifique CNRS, France), Fr. Demande 2 730 988 (1996) (Chem. Abstr., 1997, 126, 77446). M. Barbero, I. Degani, S. Dughera, R. Fochi, L. Piscopo, J. Chem. Soc., Perkin Trans. 1 1996, 289–294. S. Munavalli, D. I. Rossman, D. K. Rohrbaugh, C. P. Ferguson, H. D. Durst, J. Fluorine Chem. 1996, 76, 7–13. H. Meier, D. Gro¨schl, R. Beckert, D. Weiß, Liebigs Ann. Chem./Recueil 1997, 1603–1605. T. Takata, M. Kanamaru, T. Endo, Macromolecules 1997, 30, 6721–6726. I. Shibuya, Y. Gama, M. Shimizu, Heterocycles 1998, 48, 461–464. A. M. Sipyagin, V. V. Kolchanov, Z. G. Aliev, N. K. Karakhanova, A. T. Lebedev, Chem. Heterocycl. Compd. 1998, 34, 297–307. Gilligan W. H., (United States Dept. of the Navy, USA), U.S. Patent 5 783 732, 1998 (Chem. Abstr. 1998, 129, 148765). M. K. Bromley, S. J. Gason, M. G. Looney, D. H. Solomon, Aust. J. Chem. 1999, 52, 657–661. Takazaki, T.; Endo, T., (Zaidan Hojin Kagaku Gijutsu Senryaku Suishin Kiko, Japan), Jpn. Patent JP 11 158 182, 1999 (Chem. Abstr. 1999, 131, 31946). P. Jimonet, F. Audiau, M. Barreau, J. C. Blanchard, Y. Boireau, A. Bour, M. A. Cole´no, A. Doble, G. Doerflinger, C. Do Huu, M. H. Donat, J. M. Duchesne, P. Ganil, C. Gue´re´my, E. Honore´, B. Just, R. Kerphirique, S. Gontier, P. Hubert, P. M. Laduron, J. Le Blevec, M. Meunier, J. M. Miquet, C. Nemecek, M. Pasquet, O. Piot, J. Pratt, J. Rataud, M. Reibaud, J. M. Stutzmann, S. Mignani, J. Med. Chem. 1999, 42, 2828–2843. M. Iwamatsu, K. Ueda, T. Sugimoto, H. Fujita, Synth. Met. 1999, 102, 1617–1618. J. Fabian, A. Krebs, D. Scho¨nemann, W. Schaefer, J. Org. Chem. 2000, 65, 8940–8947. U. Jordis, K. Bhattacharya, P. Y. Boamah, V. J. Lee, Molecules 2001, 7, 145–154. N. Merkley, J. Warkentin, Can. J. Chem. 2002, 80, 1187–1195. Fries, G.; Kirchhoff, J., (Degussa A.G., Germany), Eur. Patent EP 1 207 147, 2002 (Chem. Abstr. 2002, 136, 385875). Fries, G.; Theis, C.; Kirchhoff, J., (Degussa A.G., Germany), Ger. Patent DE 10 121 116, 2002 (Chem. Abstr. 2002, 137, 325164). D. T. Vodak, M. Braun, L. Iordanidis, J. Plevert, M. Stevens, L. Beck, J. C. H. Spence, M. O’Keeffe, O. M. Yaghi, J. Am. Chem. Soc. 2002, 124, 4942–4943. V. V. Zaitseva, T. G. Tyurina, S. Yu. Suikov, S. L. Bogza, S. P. Kobzev, Russ. J. Org. Chem. 2002, 38, 588–590. Y. Zhu, D. G. Drueckhammer, Tetrahedron Lett. 2002, 43, 1377–1379. I. El-Sayed, R. G. Hazell, J. Ø. Madsen, P. O. Norrby, A. Senning, Eur. J. Org. Chem. 2003, 813–815. Kirsch, P.; Hahn, A., (Merck Patent G.m.b.H., Germany), Ger. Patent DE 10 258 577 2003 (Chem. Abstr., 2003, 139, 133074).

Functions Containing Four or Three Chalcogens

315

Biographical sketch

Alexander Senning was born in 1936 in Riga, Latvia. He studied chemistry in Munich, Germany (1954–1959) and Uppsala, Sweden (1960–1962). He obtained a Ph.D. in organic chemistry from Uppsala University in 1962. He joined the Department of Chemistry, Aarhus University, Denmark as assistant professor (1962–1965) and associate professor (1965–1993). During a sabbatical leave (1973–1975), he was head of the research laboratory of the drug company A/S Alfred Benzon, Copenhagen, Denmark. He joined the Danish Engineering Academy (DIA), Lyngby, Denmark, later part of The Technical University of Denmark (DTU), Lyngby, Denmark as professor of organic chemistry in 1993 until his retirement in 2003. Research interests: organic sulfur chemistry, medicinal chemistry. Extensive activities as book and journal editor. A detailed chemical autobiography is available in Sulfur Rep., 2003, 24, 191–253.

Jørgen Øgaard Madsen was born in 1940 in Aars, Denmark. He studied chemistry in Aarhus, Denmark (1962–1971) and received an M.Sc. (1967) and a Ph.D. (1972) in organic chemistry from Aarhus University, Denmark. He held an assistant professorship at the Department of Chemistry, Aarhus University, Denmark (1967–1971) and joined the Department of Organic Chemistry (later Department of Chemistry) of the Technical University of Denmark (DTU) as associate professor (1972 to present). Research interests: heterocyclic enamines, stereospecific syntheses with baker’s yeast, natural product chemistry, analytical organic chemistry (HPLC, MS).

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 307–315

6.11 Functions Containing Two or One Chalcogens (and No Halogens) W. PETZ and F. WELLER Universita¨t Marburg, Marburg, Germany 6.11.1 INTRODUCTION 6.11.2 DICHALCOGENOMETHANES 6.11.2.1 Methanes Bearing Two Similar Chalcogens 6.11.2.1.1 Two oxygens and a group V (15) element and/or a metalloid and/or a metal function 6.11.2.1.2 Two sulfurs and a group V (15) element and/or a metalloid and/or a metal function 6.11.2.1.3 Two seleniums or two telluriums and a group V (15) element and/or a metalloid and/or a metal function 6.11.2.2 Methanes Bearing Two Dissimilar Chalcogens 6.11.2.2.1 Oxygen, sulfur, and two functions derived from a group V (15) element, metalloid, and/or a metal 6.11.2.2.2 Oxygen and selenium, or oxygen and tellurium, and two functions derived from a group V (15) element, metalloid, and/or a metal 6.11.2.2.3 Sulfur and selenium, or sulfur and tellurium, and two functions derived from a group V (15) element, metalloid, and/or a metal 6.11.3 MONOCHALCOGENOMETHANES 6.11.3.1 Methanes Bearing One Oxygen Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal 6.11.3.1.1 Compounds with the OCN3 core 6.11.3.1.2 Compounds with the OCNP2 core 6.11.3.1.3 Compounds with the OCNSi2 core 6.11.3.1.4 Compounds with the OCNSiTa core 6.11.3.1.5 Compounds with the OCNB2 core 6.11.3.1.6 Compounds with the OCPSiTa core 6.11.3.1.7 Compounds with the OCFe3 core 6.11.3.1.8 Compounds with the OCCo3 core 6.11.3.1.9 Compounds with the OCNi3 core 6.11.3.1.10 Compounds with the OCW3 core 6.11.3.1.11 Compounds with the OCRu3 core 6.11.3.1.12 Compounds with the OCOs3 core 6.11.3.1.13 Compounds with the OCFe2Ni core 6.11.3.1.14 Compounds with the OCFe2Co core 6.11.3.1.15 Compounds with the OCFe2Rh core 6.11.3.1.16 Compounds with the OCFe2Mn core 6.11.3.1.17 Compounds with the OCRu2W core 6.11.3.1.18 Compounds with the OCW2Ru core 6.11.3.2 Methanes Bearing One Sulfur Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal 6.11.3.2.1 Compounds with the SCN3 core 6.11.3.2.2 Compounds with the SCNSi2 core 6.11.3.2.3 Compounds with the SCPFe2 core 6.11.3.2.4 Compounds with the SCPNi2 core 6.11.3.2.5 Compounds with the SCPMnRe core 6.11.3.2.6 Compounds with the SCSi3 core 6.11.3.2.7 Compounds with the SCSi2P core

317

318 318 318 318 320 332 333 333 334 334 335 335 335 336 337 337 338 338 338 338 339 340 340 340 341 341 341 342 342 342 342 342 344 345 345 345 346 346

318

Functions Containing Two or One Chalcogens (and No Halogens)

6.11.3.2.8 Compounds with the SCPSiLi core 6.11.3.2.9 Compounds with the SCSi2Li core 6.11.3.2.10 Compounds with the SCN2Fe core 6.11.3.2.11 Compounds with the SCNSnPt core 6.11.3.2.12 Compounds with the SCSiSnLi core 6.11.3.2.13 Compounds with the SCFe3 core 6.11.3.2.14 Compounds with the SCRu3 core 6.11.3.2.15 Compounds with the SCOs3 core 6.11.3.2.16 Compounds with the SCCo3 core 6.11.3.2.17 Compounds with the SCAu3 core 6.11.3.2.18 Compounds with the SCFe2Co core 6.11.3.2.19 Compounds with the SCFeCo2 core 6.11.3.2.20 Compounds with the SCCo2W core 6.11.3.3 Methanes Bearing One Selenium or One Tellurium Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal 6.11.3.3.1 Compounds with the SeCN3 core 6.11.3.3.2 Compounds with the SeCSi3 core 6.11.3.3.3 Compounds with the TeCSi3 core

6.11.1

346 347 347 347 347 347 347 348 348 348 348 348 349 349 349 350 350

INTRODUCTION

This chapter is arranged in a manner identical with that of the corresponding chapter in COFGT (1995). At first those compounds are discussed with a group V (15) element at the carbon atom followed by compounds with metalloids (other main group elements), and finally by transition metal functionality. Compounds with dissimilar atoms at the carbon atom are arranged after compounds with similar atoms.

6.11.2

DICHALCOGENOMETHANES

6.11.2.1

Methanes Bearing Two Similar Chalcogens

Dichalcogenomethanes with similar chalcogens and further atoms other than chalcogens or halogens have only been described with O2C, S2C, and Se2C; compounds with the Te2C unit had not been found up to the end of 2003.

6.11.2.1.1

Two oxygens and a group V (15) element and/or a metalloid and/or a metal function

Until 2003, compounds with the (RO)2C unit bonded to group V (15) elements other than N were not described. Further compounds were found in which this unit is connected to silicon (O2CSi2 core) and boron (O2CB2 core).

(i) Compounds with the O2CN2 core One group of compounds with this core are urea acetals; however, the majority are spiro compounds and have been reviewed earlier by Kantlehner and co-workers in COFGT (1995). The reaction of [C(NMe2)3]BF4 with the system NaH/H2NMe2/B(OMe)3 produces (NMe2)2C(OEt)2 1 along with (NMe2)C(OEt)3, (NMe2)3C(OEt) (see OCN3 core), and Me2NCOOEt as a nonseparable mixture <2000JPR256>.

Me2N NMe2 EtO OEt 1

319

Functions Containing Two or One Chalcogens (and No Halogens)

A series of spiro fused oxaziridines 2 and 3 were synthesized by reacting the corresponding semicarbazone R2C¼NNHC(O)NR0 (CH2)nOH (n = 2, 3) with PhI(OAc)2 in CH2Cl2 or CH3OH; the compounds were separated and purified by chromatography followed by bulb-to-bulb distillation; the individual compounds are collected in Table 1 <1996JA4214, 1997CJC1264, 1997CJC1281>. Theoretical studies have been done on these oxaziridines <1999CJC1340>. Table 1 R and R0 of the compounds 2 and 3 2 R

R

Sl. no

R

R0

Me Me Me Me Me Me Me Me Me Me Me

H Me C(O)H C(O)Me C(O)C(Me)¼CH2 C(O)Ph C(O)C6H4(2-OMe) C(O)C6H4(4-OMe) C(O)C6H4(4-NO2) C(O)Me SO2Ph

a b c d e

Me (CH2)5 (CH2)5 Me (CH2)5

H H Me C(O)Ph C(O)Ph

Sl. no a b c d e f g h i j k

3 0

The compound 4 is an intermediate during the photosensitized oxidation of corresponding isotopelabeled imidazole and has been characterized by low-temperature NMR spectroscopy <2002JA9629>. The spirocyclic compounds 5 and 6 were obtained by silver(I) ion-mediated desulfuration– condensation reactions of carbon disulfide with the corresponding hydroxyl compounds as colorless compounds with yields of about 75% <1998H461>.

O

N

N N

O

O

R'

R

O N R N R

3

2

R

Ph

Ph

N

N

HO

OH

4

Ph O N N O Ph

5

N

N

O

O

O

Ph

Ph

N R'

O

6

Further spiro compounds with the O2CN2 core have been reported <1997RCB(46)126, 1999RCB(48)2136>. The diazirine 7 was obtained as a solution in pentane in 70% yield in dimethylformamide (DMF) at 0 C for 1 h (Scheme 1) <1995JFC101>.

C7F15CH2O Br

N N

C7F15CH2ONa

C7F15CH2O C7F15CH2O 7

Scheme 1

N N

320

Functions Containing Two or One Chalcogens (and No Halogens)

(ii) Compounds with the O2CSi2 core The only example of a compound with this core was described recently. The reaction of (Me2PhSi)2C(SMe)2 (compound 18 with the S2CS2 core) with I2 in ethyleneglycol–acetonitrile generates the acetal 8 in 78% yield <1996CL841>. O O

SiMe3 SiMe3 8

(iii) Compounds with the O2CB2 core Only one compound with this core is reported. The reaction of the dibromobis(tetramethylethylenedioxboryl)methane with anhydrous NaAc in methylenechloride leads to the formation of the compound 9 in 25% yield <1974JOM(69)45>.

O B O AcO O B AcO O 9

6.11.2.1.2

Two sulfurs and a group V (15) element and/or a metalloid and/or a metal function

The majority of compounds in this section involve the coordination chemistry of the adduct S2CPR3 in which the two S atoms and the C atom interact with a mononuclear or dinuclear transition metal fragment in an allyl-like manner. In addition to the earlier described compounds with the S2CPMo, S2CPW, and S2CPMn core, compounds with the cores S2CPFe and S2CPCo are also now available. The coordination mode of the S2CPR3 ligand was studied earlier.

(i) Compounds with the S2CN2 core There are only a few compounds described in the literature with the S2CN2 core, and because of the different nature of the compounds a common method of preparation for these compounds cannot be formulated. The spirocyclic compounds (10a–10e) were obtained by intramolecular ring-closure by heating the appropriate starting material in tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO) as shown in Scheme 2; yields and melting points are shown in Table 2 <2000SL1464>. The similar spirocyclic compound 11 was obtained in 53% yield by the reaction of N-phenylbenzohydrazonoyl chloride with the 5-benzylidene-3-phenyl derivative of rhodamine in CHCl3 in the presence of NEt3; the structure was confirmed by an X-ray analysis (Scheme 3) <1999AX1877>.

O

O R1O S

N H

H N

R2

THF, ∆

R1O O S

O

S

S N

N

N NH H 10

Scheme 2

R2

Functions Containing Two or One Chalcogens (and No Halogens)

321

Table 2 Yields and melting points of the compounds 10a–10e Nr 10

R1

R2

Yield (%)

m.p. ( C)

a b c d e

Me Me Me Me Et

OMe OC(Me)3 OBz NH2 NHPh

85 66 77 67 68

78–81 80–83 96–99 185–188 134–137

Ph

Ph

Ph S

HN

+

O

Ph N N

Et3N

S

N

S

Ph

Ph

N S Ph

O

Cl

Ph

11

Scheme 3

Condensation between the 2-methylsulfanylthiazolium iodide and p-phenetidine in the presence of NEt3 in CH2Cl2 produces the compound 12 in about 26% yield as shown in Scheme 4 <2000JPR554>.

– F3C

S + N

I

F3C

S

p -Phenetidine

S

OEt

HN

N

S

12

Scheme 4

As shown in Scheme 5 the thiouracil reacts with P(OR)3 to produce the dithiaspirodione 13 <1996PS(119)225>.

S N

N

P(OR)3

O

N

S

N

N

S

N

O

O 13

Scheme 5

Various nitrilimines cycloadd to the C¼S bond of 3-phenyl-5-arylmethylene-2-thioxothiazolidine-4-one to give the corresponding spiro cycloadducts 14 (Ar = 4-MeOC6H4, 4-MeC6H4; R = Ph, PhC2H2, PhCO, 2-naphthoyl, 2-thienoyl, Ac, EtOCO, PhNHCO) <1996PS(113)53>. The related spiro compounds 15 were formed from the nitrilimines RCN2R1 and 3-phenyl-5phenylmethylene-2-thioxothiazolidine-4-one (R = EtCOO, Ph, Bz, 2-thenoyl, PhNHCO, styryl, 2-naphthoyl, Ac, R1 = Ph, 2-thienyl) <1995JPS205>.

322

Functions Containing Two or One Chalcogens (and No Halogens) Ar S N N

Ar O

N S Ph

O R

PhHC

15

R1 S N N S Ph

R

14

(ii) Compounds with the S2CP2 core The spiro compound 16 was reported by a Chinese working group. The compound was obtained in excellent yield by refluxing a mixture of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzodiazaphosphorin-4(1H)-one-2-oxid with CS2 in benzene <2002CCL125>.

O N

P

R

N R O S

S P O N

N O

R = CH2COOEt

16

A complex with this core was also prepared as shown in Scheme 6. Starting from the appropriate Cp2Zr complex, reaction with CS2 in toluene at 40 C gave the complex 17 in 72% yield <1999OM1882>.

Zr P Ph S S Ph P Zr

CS2 Zr

P Ph

Zr = ZrCp2 17

Scheme 6

(iii) Compounds with the S2CSi2 core The general method is the reaction of the corresponding (RS)2CH2 with BuLi followed by addition of R3SiCl to give first (RS)2CH(SiR3), which is again treated with BuLi/R3SiCl to generate the bis(dimethylphenylsilyl) ketone dithioacetal 18 in 60% yield <1996CL841>.

MeS

SiPhMe2

MeS

SiPhMe2 18

A series of spiro compounds with this core containing SiPd and SiPt bonds have been described. The reaction of 2,2-bis(disilanyl)dithiane 19 with Pd(CNBut)2 at room temperature or Pt3(CNBut)6 in refluxing benzene produces the Pd complex 20 and the Pt complex 21, respectively, in 27% yield as shown in Scheme 7; 21 was characterized by an X-ray analysis <1996JOM(521)405>. The Pd

Functions Containing Two or One Chalcogens (and No Halogens) S S S Si SiMe2Ph S Si SiMe2Ph

S

19

S

Me2 CNBut Si Pd Si CNBut Me2

20

t Me2 CNBu SiMe2Ph Si Pt SiMe2Ph Si Me2 CNBut

21

323

Scheme 7

complex 20 was also described in <1996BCJ(69)289>. Cyclic organosilicon compounds 22 (R = Ph, SiMe3; R1 = H) were obtained upon bis-sylilation of RCCR1 compounds with cyclic bis(organosilyl)palladium intermediates <1996BCJ(69)289>.

Me2 R S Si 1 S Si Me2 R

22

(iv) Compounds with the S2CSiSn2 core Only one compound with this core was described. Compound 23 was prepared by adding butyllithium to a stirred solution of 2-trimethylsilyl-1,3-dithiane in THF; then a THF solution of Sn(3-C5H5)(-N¼C(NMe2)2) was added. Yellow crystalline blocks were obtained in 29% yield. The compound is dimeric containing a four-membered SnNSnN ring and was characterized by an X-ray analysis <1995JCS(D)1587>.

S

Me3Si

S NMe2

Me2N

Sn

N

N

Sn

NMe2

Me2N S SiMe3

S 23

(v) Compounds with the S2CGe2 core Related to the heterocycles with the S2CSi2 core, 20 and 21, the corresponding Ge-derivatives have been prepared in a similar procedure as shown in Scheme 8. Thus, the corresponding compound 24 reacts with Pd(CNBut)2 at room temperature to produce quantitatively the Pd complex 25. With Pt3(CNBut)6 in refluxing benzene the Pt complex 26 was formed in 30% yield along with 27 as a by-product; the compounds 25 and 27 were characterized by X-ray analyses <1996JOM(521)405>.

324

Functions Containing Two or One Chalcogens (and No Halogens) S S S Ge SiMe2Ph S Ge SiMe2Ph

S

24

S S L = CNBut

S

Me2 L Ge Pd L Ge Me2

25

Me2 L SiMe2Ph Ge Pt SiMe2Ph Ge Me2 L

26

Me2 L Ge Pt Ge Me2 L

27

Me2 Ge S Ge S Me2

Scheme 8

(vi) Compounds with the S2CSn2 core Two more compounds of this type are described in the literature. Compound 28 was prepared according to Scheme 9 in 94% yield by insertion of the corresponding dithiacarbene (prepared in situ) into the tintin bond of Me6Sn2; the compound was characterized by an X-ray structure analysis. The related compound 29 was obtained in 48% yield by the reaction of the appropriate carbanion with Me3SnCl <1996PAC853>. S C: S

S SnMe 3

Me6Sn2

S – SnMe3

28

S SnMe3

Me3SnCl

S

S SnMe3 SnMe3 S

29

Scheme 9

(vii) Compounds with the S2CNa2 core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (vi)).

(viii) Compounds with the S2CNSi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (vii)).

(ix) Compounds with the S2CNP core A [3 + 2]-cycloaddition of an in situ generated nitrilium phosphane ylide complex with benzyl N,N-dimethyl dithiocarbamate ester generates the thiaphosphirane 30 as a pale yellow oil in 13% yield as shown in Scheme 10; R denotes ubiquitous organic substituents <1999CC499>.

Functions Containing Two or One Chalcogens (and No Halogens)

W(CO)5 pip C N P R

BzS(NMe2)CS –pipCN, –W(CO)5

Me2N

325

R P S

BzS 30

Scheme 10

(x) Compounds with the S2CPSi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (viii)).

(xi) Compounds with the S2CSiGe core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (ix)).

(xii) Compounds with the S2CSiLi core In addition to the compounds with this core reported earlier, the solution ion pair structure of 2-lithio-1,3-dithianes in THF and THF–HMPTA were studied. From low-temperature multiNMR studies, it was found that in THF the compounds are contact ion pair species and become separated ions with excess HMPTA. The compounds 31 (R = Me, Ph) were obtained from the appropriate substituted 1,3-dithianes and BuLi <1994T5869>. S

Li

S

SiMe2R 31

(xiii) Compounds with the S2CSnLi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (xi)).

(xiv) Compounds with the S2CPCr core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2 (xii)).

(xv) Compounds with the S2CPMo core The coordination chemistry of the adduct S2CPR3 (R = Me, Et, Cy) and various molybdenum compounds has been explored by Miguel and co-workers. This ligand coordinates in an 3-pseudoallylic manner to one or two transition metals or to one transition metal and a main group element with formation of an S2CPM core. Molecular orbital (MO) analysis of the fluxional behavior of M(S2CPMe3)(CO)2(PMe3)2 complexes (M = Mo, W) was studied in <1996IC2406>. The Br-bridged complex of the general formula (CO)3M0 (-Br)(-S2CPR3)M(CO)3 (where M0 = Re and M = Mo) was a starting complex for various other species. The complex 32 (Scheme 11, R = Cy) can be reduced with Na/Hg at 78 C in THF to an anionic species, which by subsequent addition of Ph3SnCl gives the yellow complex 33; on warming to room temperature, 33 is reversibly converted into the red compound 34 and an equilibrium of 4/5 of both complexes is reached at room

326

Functions Containing Two or One Chalcogens (and No Halogens)

temperature; both compounds were studied by X-ray analyses <1999OM490>. Reduction of 35 with Na/Hg in THF produces the anion 36 with formation of an MoMn bond (Scheme 12). The addition of ClSnPh3 causes migration of the central carbon atom of the S2CPR3 ligand from Mo to Mn to give compounds 37 with the S2CPMn core, which are converted into 38a–38d on addition of the ligands dmpm or tedip. The same reaction sequence occurs, if two CO groups are replaced in 35 by the chelating ligands dmpm or tedip to give 39a–39d and 40a–40d (see Table 3) <1995JOM(492)23>. Further, 35 reacts with NaCCPh and NaCCH to give the acetylene-bridged derivatives 41 and 42, respectively, in high yields (Scheme 13), which were characterized by X-ray analyses <1998JA417>. The Br-bridged complex 43a (M = Mo) is shown in Scheme 14; the Mo complex (see also compound 43b with S2CPW core) was obtained with Mo(CO)3(NCMe)3 in 90% yield. The complex 43a with the MoBrMo arrangement reacts with monodentate ligands to give nearly quantitatively the related complexes 44 or with chelating ligands to produce the complexes 45 in 60% and 80% yields, respectively. The crystal structure of 44 (L = PEt3) is shown <1997JOM(545-546)327>. PR3

S S

Mo(CO)3

(OC)3Re

i. Na[Hg] ii. Ph3SnCl

Br 32 PR3

S

S

Ph3Sn

(OC)3Re

PR3

S

S

(OC)2Re

Mo(CO)3

Mo(CO)3 C

SnPh3

O

33 34

Scheme 11

– PR3

S S

Mo(CO)3

(OC)3Mn 36

S

ClSnPh3

Na[Hg]

(OC)3Mn

–

OC CO 37

PR3

S S

L–L

Mo

(OC)3Mn PR3

S

L

S

Br L

Mn(CO)3

OC

Br 35

(OC)2Mn

Ph3Sn

S Mo

Mo(CO)3

Mo

PR3

S

PR3

S

CO CO

L–L

CO CO L

Na[Hg] 40

ClSnPh3 S OC Ph3Sn OC

L L

L = dmpm, tedip

39

Scheme 12

PR3

S

CO

Mo

Mn

L

L

CO 38

Functions Containing Two or One Chalcogens (and No Halogens)

327

Table 3 R and chelating ligand of the compounds 38, 39, and 40a–40d 38, 39, 40

R

L–L

a b c d

Cy Pri Cy Pri

tedip tedip dmpm dmpm

PR3

S S (OC)3Mn

PR3

S

Mo(CO)3

S

Br 35

NaCCH (OC)3Mn NaCCPh

C C

PR3

S

Mo(CO)3

S

Mn(CO)3

(OC)3Mo

(OC)3Mn

Mo(CO)3

S S

R3P

C

R = Cy

CPh 41

42

Scheme 13

OC

S

M(CO)3(NCMe)3

S Mo

OC

PCy3

S

NO PCy3

M(CO)3

(ON)(OC)2Mo

S

Br

Br

43 (a, M = Mo; b, M = W) L–L

L

PCy3

S PR3

S

S

S Mo

(ON)(OC)2Mo (ON)(OC)2Mo

Mo(CO)2L Br L

Br L = PEt3 L = P(OMe)3

CO CO L

L–L = Me2PCH2PMe2 L–L = Ph2PCH2PPh2

44

45

Scheme 14

Reactions of 35 with Br bridge replacement are depicted in Scheme 15. The reaction of 35 with NaOMe in methylenechloride generates 46 in about 80% yield containing an OMe bridge instead of a Br bridge. The OMe bridge can easily be replaced by carbon acids to produce the related complexes 47 in yields between 30% and 60%, while the action of ethanolamine generates

328

Functions Containing Two or One Chalcogens (and No Halogens)

48 in 46% yield. The S-bridged complex 49 was obtained by the reaction of 35 with the salt [HSCH2CH(COOMe)NH3]Cl in 41% yield; most of the complexes were studied by X-ray analysis <2002OM2979>. PCy3

S

PCy3

S

S

S NaOMe

46

Mo(CO)3

(OC)3Mn

Mo(CO)3

(OC)3Mn

Br

O Me

35

PCy3

S

PCy3

S

S (OC)3Mn

Mo(CO)2

PCy3

S

S

S Mo(CO)2

(OC)3Mn

O

R2

R

H

Me

H

H

Ph

H

H

Bz

H

Me

Me

H

H

H

Me

Mo(CO)2

(OC)3Mn SH

O NR2

R1

NH2

NH2

O R1

R2

COOMe

47

48

49

Scheme 15

Replacement of the Br bridge by other ligands starting from the dinuclear complex 35 (R = Pri) is also shown in Scheme 16. Thus, Na/Hg reduction generates the anion 36, which can be converted with PhSeI in THF into red crystals of 50 (82% yield, crystal structure). Similarly, with –

PR3

S

S

S

S

Na[Hg] Mo(CO)3

(OC)3Mn

PR3

(OC)3Mn

Br

Mo(CO)3 36

35

PhSeI

Ph2PCl

PR3

S

PR3

S S

S

Ph3SnCl (OC)3Mn

Mo(CO)3

Mo(CO)3

(OC)3Mn P

Se Ph

Ph

50

Ph 51

PR3

S S

CH2Cl2, reflux

S

PR3

S Mn(CO)3

(OC)3Mn Ph

Mn(CO)3

(OC)3Mo

P Ph

Ph3Sn

52

Scheme 16

53

Functions Containing Two or One Chalcogens (and No Halogens)

329

Ph2PCl, brown crystals of 51 (76% yield) were obtained which on heating rearrange and give 52 with the S2CPMn core in 86% yield. Heating of 36 and addition of Ph3SnCl rearranged to give 53, which was confirmed by an X-ray analysis <1994OM4667>.

(xvi) Compounds with the S2CPW core MO analysis of the fluxional behavior of M(S2CPMe3)(CO)2(PMe3)2 complexes (54, M = Mo, W) was studied in <1996IC2406>. PMe3

S S M OC

PMe3 PMe3

CO

54

The dinuclear nitrosyl complex 43b (M = W) with an MoBrW arrangement was obtained in 86% yield by the reaction of (CO)2(NO)BrMo(S2CPPCy3) with W(CO)3(NCMe)3 in THF as shown in Scheme 14; for the related Mo complex, see compounds with the S2CPMo core <1997JOM(545-546)327>. Cationic carbyne complexes with this core are also described. As shown in Scheme 17, two CO groups and MeCN are replaced in the starting carbyne complexes (n = 1, 4) by the reaction with S2CPCy3 for 24 h in MeOH at room temperature; the compounds 55 were obtained in 90% yield; the complex with n = 1 was characterized by an X-ray analysis <1997OM4099>.

CO CO MeCN W P P C

H

PCy3

S S

[BF4]

[BF4]

W S2CPCy3

(CH2)n

P

P

C

H

(CH2)n 55

Scheme 17

(xvii) Compounds with the S2CPMn core Compounds with this core are only known with the S2CPR3 ligand bonded in an 3-manner and bridging two transition metals. As depicted in Scheme 18, the neutral complexes 56 (M = Mn) and 57 (M = Re) can be reduced with Na[Hg] to produce anionic species (structure not reported), which undergo protonation reactions <1998OM3448>. For further compounds with an S2CPMn core, see migration of the central carbon atom from Mo to Mn to give 37 and 38 as shown in Scheme 12 <1995JOM(492)23> and the compounds 52 and 53 in Scheme 16 <1994OM4667>.

(xviii) Compounds with the S2CPRe core For an Re complex with this core, see also compound 57 in Scheme 18. The complexes 58 (R = Cy, Pri) were obtained in about 55% yield by heating the appropriate S2CPR3 bridged

330

Functions Containing Two or One Chalcogens (and No Halogens) PR3

S S

Na[Hg]

(OC)3M

[M2(CO)6(S2CPR3]2–

M(CO)3

M R 56, Mn Cy 56, Mn Pri 57, Re Cy

Scheme 18

dinuclear octacarbonyl compounds in octane or toluene at reflux temperature during conversion of the ligand from an 2- into an 3-coordination, as shown in Scheme 19; the cyclohexyl derivative was confirmed by an X-ray analysis <1997CB1507>. The preference of 3-Mn coordination over 3-Re coordination in an MRe(CO)6(3-S2CPR3) complex has been studied <1999OM490>. PR3 PR3

S S

Toluene, reflux

S

S

Re

Re

(OC)3Re

Re = Re(CO)4

Re(CO)3

58

Scheme 19

(xix) Compounds with the S2CPFe core Mononuclear complexes with this core have been described by Miguel and co-workers as depicted in Scheme 20. The complex 59 (R = Cy, Pri) could be obtained in 40% yield by reacting Fe(BDA)(CO)3 with S2CPR3 in CH2Cl2 solution. The complex with R = Cy was characterized by an X-ray structure analysis. Alkylation with CF3SO3Me produced the corresponding cationic complexes 60; a crystal structure of 60 (R = Cy) was obtained <1996OM2735>. Me S Ph

O

S2CPR3

S

Fe OC

+

Me PR3

S CF3SO3Me

S

Fe CO

CO

OC

PR3

Fe CO

CO

59

OC

CO CO

60

Scheme 20

(xx) Compounds with the S2CPCo core The first compounds with an S2CPCo core are reported (Schemes 21 and 22). Starting from various Mn or Re complexes with the chelating S2CPR3 ligand, with Co2(CO)8 or Na[Co(CO)4] a variety of mixed dinuclear complexes (61a–61d) with CoMn and CoRe bonds are obtained in about 80% yield; an X-ray analysis was performed on 61 (M = Mn, R = Cy). The preparation of the complexes 62 with an allylic ligand and MoCo and WCo bonds from the related mononuclear complexes and Co2(CO)8 are depicted in Scheme 22; the structure of the complex 62 with M = Mo and R = Cy was confirmed by an X-ray analysis <1994OM2330>.

Functions Containing Two or One Chalcogens (and No Halogens)

331

Br OC

S PR3

M OC M Mn Mn Re Re

S

Co2(CO)8

CO

R Cy Pri Cy Pri

PR3

S S (OC)3M

Br OC

S Re

Na[Co(CO)4]

PR3

OC

Co(CO)2 61

S CO

a b c d

M Mn Mn Re Re

R Cy Pri Cy Pri

Scheme 21

PR3

S Br Co2(CO)8

S M OC

S

PR3

M

S

OC

CO

Co(CO)2

CO 62

a b c d

M Mo Mo W W

R Cy Pri Cy Pri

Scheme 22

(xxi) Compounds with the S2CPNi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2.(xvi)).

(xxii) Compounds with the S2CPPt core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2.(xvii)).

(xxiii) Compounds with the S2CFe2 core The reaction of the cationic complex cis-[Cp2Fe2(-CS)(-CSMe)(CO)2]+ with Na[S2CNMe2] affords the dithiocarbene complex 63 along with a carbyne complex <2002JOM(659)15>. With nucleophiles RS (R = Me, Ph, CH2Ph), the related -carbene complexes 64 were obtained <1989OM521>. MeS

NMe2

S

Fe

Cp(OC)Fe

S Cp

C S 63

332

Functions Containing Two or One Chalcogens (and No Halogens)

MeS

SR

Cp(OC)Fe

Fe(CO)Cp C O 64

(xxiv) Compounds with the S2CFeCo core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2.(xix)).

(xxv) Compounds with the S2CCoRu core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.2.(xx)).

6.11.2.1.3

Two seleniums or two telluriums and a group V (15) element and/or a metalloid and/or a metal function

(i) Compounds with the Se2CSi2 core A series of bicyclic compounds containing SeSe bonds have been described, which were obtained by the reaction of bis(silyldiazamethyl)polysilanes with elemental Se. Thus, Se-bridged six-membered rings (65a–65b) and seven-membered rings (66a–66c) were reported <1996G147>. SiMe3

SiMe3

Se

Me2Si

Se

Me2Si

Se Me2Si

Se Me2Si

Se

Se

65a

SiMe3

65b

SiMe2Ph

SiMe2

Se Se

SiMe2Ph

Se

SiMe2

Se

SiMe2

Se

Se

SiMe2

66a

SiMe2

SiMe3

SiMe2

Se Se

Se

SiMe2 PhMe2Si

SiMe2 SiMe2

Me3Si

66b

66c

(ii) Compounds with the Se2CSiLi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.3.(ii)).

Functions Containing Two or One Chalcogens (and No Halogens)

333

(iii) Compounds with the Se2CPPd core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.1.3.(iii)).

6.11.2.2

Methanes Bearing Two Dissimilar Chalcogens

Dichalcogenomethanes with dissimilar chalcogens and further atoms other than chalcogens or halogens are known with the OSC and SSeC units.

6.11.2.2.1

Oxygen, sulfur, and two functions derived from a group V (15) element, metalloid, and/or a metal

(i) Compounds with the OSCN2 core The spirocyclic compounds (67a–67e) were obtained via a one-flask reaction of the corresponding 1,2-diaza-1,3-butadienes with oxazolidine-2-thion in THF at room temperature as shown in Scheme 23; yields and melting points are shown in Table 4 <2000SL1464>.

S OR1

O

O

O NH

R1O O S

N N

O

R2

N

N NH H

R2

O 67

Scheme 23

Table 4 Yields and melting points of the compounds 67a–67e Nr 67

R1

R2

Yield (%)

m.p. ( C)

a b c d e

Me Me Me Me Et

OMe OC(Me)3 OBz NH2 NHPh

69 78 67 79 80

147–150 126–128 105–108 180–185 145–148

(ii) Compounds with the OSCSi2 core The O,S-acetal (Me3Si)2C(OMe)(SPh) 68 was obtained by reacting methoxy(phenylthio)methane with BusLi in THF in the presence of TMEDA followed by addition of Me3SiCl <1986JOC879>; reactions of the compound are described in <1998SC1415, 1998ACS1141>. MeS

SiMe3

MeO

SiMe3

68

The preparation of this fluoro-substituted benzoxathiol–1,1-dioxide 69 was described in <1996AP(329)361>.

334

Functions Containing Two or One Chalcogens (and No Halogens) O O S SiMe3

MeO

O

F

SiMe3

69

(iii) Compounds with the OSCSiGe core Treatment of HC(SPh)(GeMe3)(OMe) with BuLi in THF solution at 78 C followed by addition of Me3SiCl in THF produced the compound (Me3Si)C(SPh)(GeMe3)(OMe) 70 in 90% yield <2000JCS(P1)2677>.

PhS

GeMe3

MeO

SiMe3

70

(iv) Compounds with the OSCGe2 core Treatment of HC(SPh)(GeMe3)(OMe) with BuLi in THF solution at 78 C followed by addition of Me3GeCl in THF produced the compound C(SPh)(GeMe3)2(OMe) 71 in 46% yield; the use of Me3GeBr increased the yield to 92% <2000JCS(P1)2677>.

PhS

GeMe3

MeO

GeMe3

71

(v) Compounds with the OSCSiLi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.2.1.(iii)).

6.11.2.2.2

Oxygen and selenium, or oxygen and tellurium, and two functions derived from a group V (15) element, metalloid, and/or a metal

Compounds with OSeC or OTeC fragments with adjacent group V elements, metalloids or transition metals have not yet been described and no further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.2.2).

6.11.2.2.3

Sulfur and selenium, or sulfur and tellurium, and two functions derived from a group V (15) element, metalloid, and/or a metal

(i) Compounds with the SSeCSiLi core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.2.3.(i)).

Functions Containing Two or One Chalcogens (and No Halogens)

335

(ii) Compounds with the SSeCFe2 core The only compound in this series is reported by Angelici and co-workers and it contains the carbene ligand CSR(SeR0 ) coordinated at a metal in a bridged manner. Thus, the reaction of the chemically generated radical [Fe2Cp2(CO)2(-CSMe)]_ with PhSeSePh in THF solution at 20 C produced the carbene complex 72 in 31% yield <1986JA3688>. The complex is also obtained by reacting the cationic complex [Fe2Cp2(CO)2(-CSMe)]_+ with the nucleophile PhSe; see also compounds with the S2CFe2 core <1989OM521>. MeS

SePh

Cp(OC)Fe

Fe(CO)Cp C O 72

(iii) Compounds with the SSeCPPd core No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.2.2.3.(ii)).

6.11.3

MONOCHALCOGENOMETHANES

The majority of compounds in this section contain a 3-CER carbyne ligand (E = chalcogen) bridging a triangular face of a transition metal cluster compound. R can also be a 16- or 17-electron transition metal fragment, e.g., C5H5Fe(CO)2, Mn(CO)5, etc. In this case the CE unit can be considered as 4-bridging. Not included are cluster compounds in which only the 16-electron ligand CE coordinates at an appropriate trinuclear cluster in a 3-manner. The bonding of a CER fragment to the main group elements is restricted to a few examples bearing mainly the OCN3 core. The compounds are arranged in a manner that the CER fragment (E = chalcogen) is bonded to three identical main group elements, mixed main group elements, mixed main group transition metal elements, three identical transition metal elements, and different transition metal elements.

6.11.3.1

6.11.3.1.1

Methanes Bearing One Oxygen Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal Compounds with the OCN3 core

The reaction of [C(NMe2)3]BF4 with the system NaH/H2NMe2/B(OMe)3 produces (NMe2)3C(OEt) 73 along with (NMe2)2C(OEt)2 1, (NMe2)3C(OEt) and Me2NCOOEt as a nonseparable mixture; similar for (NMe2)3C(OEt) 74 <2000JPR256>. Me2N NMe2 EtO NMe2

73

Me2N NMe2 MeO NMe2

74

The compound 75 was obtained in 90% yield by the reaction of the related ionic triazole derivative with methanol in the presence of K2CO3; the related compound 76 was detected during

336

Functions Containing Two or One Chalcogens (and No Halogens)

the thermolysis of CF3C(O)N¼C(NPri2)OCOCF3 and characterized by NMR studies; see Scheme 24 <1997JOC9070>.

NPr2i N

NPr2i

MeO

N

N

N 75

NPr2i

Pr2N + N SO2CF3

NPr2i N SO2CF3

Pr2N

SO2CF3– NPr2i

F3COCO O F3C

OCOCF3

N

NPr2i

N

N CF3

O

F3C

76

Scheme 24

The compounds 77 (R = H, Ac) were obtained from hydrolysis of the corresponding imidazolones as shown in Scheme 25 <1996JCS(P2)371>. The compound 77 (R = H) was also obtained in 18% yield from a photosensitized oxidation process of the corresponding guanidine compound <1999EJOC49>; see also <1998JA10283>.

H N

O

N O

NH

HN

RO

H2N H2N RO

RO

O

O

N O

NH

RO 77

Scheme 25

The preparation of various heterocyclic compounds were reported; the compounds 78 were obtained by the reaction of the appropriate nitrone with RCNX compounds in CH2Cl2 in 70–90% yield (X = O; R = ClCH2CH2, a-naphthyl; X = S, R = Ph) <2001RCB882>. The triazine 79 was obtained as a by-product (15% yield) during the reaction of [C(NH2)3]Cl with C3F7CF¼NC4F9 in MeCN in the presence of NEt3 <2001RCB476>.

N O

Ph N

O

C3F7

X

N R

78

6.11.3.1.2

N N

OH N N

C3F7 N

C3F7 C3F7

79

Compounds with the OCNP2 core

The phosphonic acid derivative 80 was used as a biochemical inhibitor; no preparation was given <2001BBR(287)468, 1999BJ(337)373>. The related compounds 81 were used as compounds interacting with HIV-1 reverse transcriptase <2001MB(35)717>.

Functions Containing Two or One Chalcogens (and No Halogens) R (HO)2OP HO

H N

337

O

O N (HO)2P H N HO P(OH)2 OH O

SPh

PO(OH)2 80

81 R = PO(OH)2, H

6.11.3.1.3

Compounds with the OCNSi2 core

Compounds with this core are shown in Scheme 26 and have been obtained from the appropriate benzotriazole in various yields together with other products by the reaction with lithium diisopropylamide (LDA) and trimethylsilyl chloride at 78 C. Exhaustive silylation leads to 82 with yields up to 86%. Silylation of 83 produces 82 in high yields <1999T11903>; the preparation of 83 was also described in an earlier report <1995TL6321>.

N N N

83

R Me3Si

SiMe3

N N

LDA, TMSCl

N

LDA, TMSCl

R SiMe3 N N

82

N Me3Si

R SiMe3

R = OMe, OCD3, OPh, OC2D5

Scheme 26

The four-membered ring compound 84 was obtained in 52% yield by the photochemically induced addition of MeOH on the corresponding trisilacyclobutanimine (Scheme 27) <1992JOM(441)185>.

R2 Si SiR2 R2Si

MeOH

NPh

OMe Ph NH R2Si R2Si SiR2

84

R = But

Scheme 27

6.11.3.1.4

Compounds with the OCNSiTa core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.2).

338 6.11.3.1.5

Functions Containing Two or One Chalcogens (and No Halogens) Compounds with the OCNB2 core

Only one compound with this core is described. The reaction of the three-membered ring compound NB2R3 (R = But) at 78 C with CO produces the tricyclic spiro compound 85 as depicted in Scheme 28 <2002ZAAC1631>.

RN BR RB

RB RN

CO

O BR RB O

NR BR

85

R = But

Scheme 28

6.11.3.1.6

Compounds with the OCPSiTa core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.3).

6.11.3.1.7

Compounds with the OCFe3 core

The related section in chapter 6.11.3.1.4 in COFGT (1995) includes compounds in which the 3-bonded COR group bridges the face of a triangular cluster or one face of a tetrahedral cluster, contributing three electrons to the number of 48 or 60 CVE, respectively. Only one new example of a triangular cluster has been described. The trinuclear complex 86 (NR2 = NBut(SiMe3), X = Cl) was obtained in 62% yield by the reaction of [Fe3(CO)11]2 with Cl2BNBut(SiMe3) in benzene <1999EJIC2277>. X B

NR2

O

Fe(CO)3

(OC)3Fe

Fe(CO)3

O R2N

B X 86

6.11.3.1.8

Compounds with the OCCo3 core

This section contains compounds that are based on the trinuclear cluster Co3(CO)9(3-COR), in which R represents various organic substituents including main group or transition metal elements. Starting materials are mainly Co2(CO)8, MCo(CO)4, or the covalent trinuclear cluster Co3(CO)9(3-COLi). Thus, the reaction of NaCo(CO)4 with (acac)3ZrCl in toluene generates the complex [(acac)3Zr-OCCo3(CO)9] 87 in 60% yield <2000JOM(604)68>. The similar reaction with AlCl3 in benzene gave [(THF)3AlOCCo3(CO)9{Co4(CO)13}] 88 <1994ZN(B)1549>. The mixed salt

Functions Containing Two or One Chalcogens (and No Halogens)

339

[Et4N][Cl2SiOCCo3(CO)9{Co4(CO)11}] 89 was prepared as a minor compound during the reaction of Si2[Co2(CO)7]2 with [Et4N][Co(CO)4] <1992AX(C)1204>. All the compounds were characterized by X-ray analyses. Zr(acac)3 O

Co

Co

Co = Co(CO)3

Co

87

Co Co

THF O THF Al THF

Co

O

Co

O

Co

Co

Co = Co(CO)3

Co 88

Co1

Cl Cl

Si

-

O

Co

Co

Co = Co(CO)3 Co1 = Co4(CO)11

Co

89

6.11.3.1.9

Compounds with the OCNi3 core

The reaction of K[CpNiCO] in toluene with a series of boron compounds of the type ClB(NR2)X leads to the trinuclear Ni cluster compounds 90 (a: NR2 = NBut(SiMe3), X = Cl; b: NR2 = N(SiMe3)2, X = Cl; c: NR2 = NMe2, X = BNMe2Cl) in low yields of about 15% <1999EJIC2277>. X B

NR2

O

NiCp

CpNi

NiCp C O

90

340 6.11.3.1.10

Functions Containing Two or One Chalcogens (and No Halogens) Compounds with the OCW3 core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.6).

6.11.3.1.11

Compounds with the OCRu3 core

Two new compounds with this core were prepared. Starting from [Ru3H3(CO)9(3-COMe)], addition of the appropriate Au complexes [Au{-Ph2P(CH2)nPPh2}Me2] (n = 1, 5) in ether gave the mixed-metal cluster complexes 91 and in about 30–40% yield; both compounds were characterized by X-ray analyses <1998JCS(D)1107>.

O OC

Ru Ru H Ru Au

OC P

Au P 91

Ru = Ru(CO)3 P

P = PPh2(CH2)nPPh2; n = 1, 5

In <1995OM481> the tetranuclear cluster [Ru3Pt(-H)(3-COMe)(CO)10(PR3)] 92 is described, obtained from the reaction of [Ru3(-H)(-COMe)(CO)10] with PtPR3(nb)2 (R = Cy, Pri), but according to the crystal structure, the carbyne group COMe is asymmetrically bonded directing to a -bridging group (two short RuC bonds, 199 and 197 pm and one long bond, 260 pm).

O

Ru

Ru

Ru

H

Pt CO

R3P

Ru = Ru(CO)3 92

6.11.3.1.12

Compounds with the OCOs3 core

The anionic complex 93 was obtained as yellow crystals from the reaction of [Os3H3(CO)9(3-COMe)] with 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) in CH2Cl2 in 87% yield. Further reaction with [AuPPh3]Cl/TlPF6 gave the cluster compound 94 in 85% yield as depicted in Scheme 29 <1992JCS(D)1701>. The hexanuclear cluster 95 was obtained in 32% yield from the reaction of [Os6(CO)16(MeCN)2] with 1 equiv. of pyridine in

Functions Containing Two or One Chalcogens (and No Halogens)

341

CH2Cl2 solution at room temperature; the cluster was characterized by an X-ray analysis <1997JCS(D)4357>.

O

O

– H Os H

H Os H

Os Os

H

Os Os

93

O

H Os H

Os = Os(CO)3 Os AuPh3

Os 94

Scheme 29

Os(CO)2(py)2

O

Os(CO)2

py(OC)2Os

Os Os

Os

Os = Os(CO)3

95

6.11.3.1.13

Compounds with the OCFe2Ni core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.9).

6.11.3.1.14

Compounds with the OCFe2Co core

The cluster 96 was obtained in 62% yield by addition of HgPh2 to a solution of Fe2Co(H)(-COMe)(CO)7Cp in toluene; the compound was characterized by an X-ray analysis <1992OM540>.

6.11.3.1.15

Compounds with the OCFe2Rh core

For the structure of the Rh cluster 97 with this core, see the related Co cluster 96. The cluster was obtained in 55% yield by addition of HgPh2 to a solution of Fe2Rh(H)(-COMe)(CO)7Cp in toluene; the compound was characterized by an X-ray analysis <1992OM540>.

342

Functions Containing Two or One Chalcogens (and No Halogens)

O

O

Fe

(OC)CpM

Fe

Fe Hg

MCp(CO)

Fe

Fe = Fe(CO)3 96 (M = Co) 97 (M = Rh)

6.11.3.1.16

Compounds with the OCFe2Mn core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.12).

6.11.3.1.17

Compounds with the OCRu2W core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.13).

6.11.3.1.18

Compounds with the OCW2Ru core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.1.14).

6.11.3.2

Methanes Bearing One Sulfur Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal

The compounds in which two or three different elements are attached to the SC carbon atom are rare and only realized in some examples. Main group compounds concentrate with few exceptions on species with the SC(SiMe3)3 fragment. The majority of samples in this section, however, are based on M3 cluster compounds with a 3-C¼S ligand or similar clusters in which one or two Co atoms are replaced by other transition metals; addition of an electrophile at the C¼S sulfur atom gives a 3-methylidine ligand, which contributes three electrons to the cluster.

6.11.3.2.1

Compounds with the SCN3 core

A series of heterocyclic compounds with this core were prepared recently. The reaction of N-[(trimethylsilyl)methyl]imminium triflate with various imines in the presence of CsF gave the compounds 98 in 40% to 70% yields as depicted in Scheme 30. Similarly, the reaction of the triflate with diethyl azodicarboxylate generated the compounds 99 in yields between 20% and 74% <2001H243>. A new series of transition metal complexes was prepared containing the tris(pyrazoly)methansulfonato ligand 100 (Tpms). Toward transition metals, Tpms can act as a bidentate or, tridentate ligand. This new ligand was prepared as the Tl salt by adding excess of Tl2CO3 to an aqueous solution of LiTpms. Recrystallization from methanol gave 60% yield <2000AG2464, 2001EJIC1415>. The complex 101 was obtained from the reaction of TlTpms with [Rh(CO)2Cl]2 under 2–3 atm CO in THF is quantitative yield; without a positive CO pressure,

343

Functions Containing Two or One Chalcogens (and No Halogens) Ar HC N

H N Ts

98

NHPh

N

Ar

Me3Si

SMe

Ts

N SMe

E

PhHN

N N E

H N E

SMe 99

NHPh

N N E

Ar = Ph, p -ClC6H4, p -NO2C6H4 E = COOEt

Scheme 30

the dinuclear complex 102 was formed quantitatively. If the reaction was carried out with [Rh(cod)Cl]2 in CH2Cl2, the complex 103 (dien = cod) was obtained. Similarly, the reaction of TlTpms with [Rh(nbd)Cl]2 in dichloromethane generated the complex 104 (dien = nbd). Addition of PPh3, PMe3, or PCy3 to 101 produced the complexes 105a–105c (PR3 = PPh3, PMe3, PCy3). With potassium diphenyl(sulfonatophenyl)phosphane 106 was obtained in 40% yield. Most of the complexes have been characterized by X-ray analyses <2001EJIC1415>. The complex 105 (R = PMe3) activated benzene upon irradiation to form 107, which was carbonylated with CO to give 108; the reactions are collected in Scheme 31 <2001EJIC3113>. Treatment of CuCl in EtOH/ MeCN with LiTpms and PPh2C6H4COOH-4 produced the complex 109 in 76% yield <2003JIB(94)348>.

N

N S

S

N Rh

N

N

CO

S

N

N

N N Rh

N

PR3

S

_

N N

PPh2PhSO3

Rh(dien)

CO

CO 105

104

106 N

C6H6 S

103 CO

N N

PMe3 Rh

Ph

N N

S N

108

107

SO3 N N

N N

= S

PMe3 Rh

COPh H

H

–

N

Rh

N

Rh

S

N

102

N

N

C O C O

K[PPh2PhSO3]

PR3

N

Rh

CO

101

S

N O C

N

N N

N

100 = Tpms

Scheme 31

344

Functions Containing Two or One Chalcogens (and No Halogens) COOH N S

N

S

S N

N N N

N

N N PPh2 N Cu PPh2

N COOH 109

111

The compounds 110 in Scheme 32 contain the MFe3S4 cluster and are obtained as the [Me4N]2[VFe3S4R4] salts. The chloro derivative 110 (R = Cl) was obtained in 38% yield from the DMF complex by reacting with LiTpms in acetonitrile followed by addition of Me4NCl. Further reaction with NaSR compounds generates 110 (R = SEt) and 110 (R = S-Tol-p) in 48% yield; similarly, the action of NaO-Tol-p produces the complex 110 (R = O-tol-p) <2002IC958>.

R Fe S

DMF

S

R S

Fe

Fe S Fe

V

DMF

R

R

Fe S Fe

S R

S

V

N N

DMF

S

R

N

S

110

–SO 3 N N

N

N

N N

= S

N N

N

100

Scheme 32

The formation of the compound 111 was mentioned in <2001AG1247>.

6.11.3.2.2

Compounds with the SCNSi2 core

The reaction of BtCHSMe(SiMe3) with BuLi followed by subsequent addition of Me3SiCl afforded the compound 112 according to Scheme 33 <2000JOC9206>.

N

N

N

BuLi, Me3SiCl

N

N

N Me3Si

Me3Si

SMe

SMe SiMe3

112

Scheme 33

Functions Containing Two or One Chalcogens (and No Halogens) 6.11.3.2.3

345

Compounds with the SCPFe2 core

The cationic complex [Cp2Fe2(CO)2(-CSMe)]+ was allowed to react with ButP(H)SiMe3/DBU in MeCN to give the unstable complex 113, which loses CO to produce finally black 114 in 36% yield, which was characterized by an X-ray analysis as depicted in Scheme 34 <1997ZN(B)655>. Me

Me

PHBut

S

PHBut

S

Cp(OC)Fe

–CO

Fe(CO)Cp

CpFe

Fe(CO)Cp C O

C O

114

113

Scheme 34

6.11.3.2.4

Compounds with the SCPNi2 core

The dinuclear nickel complex 115 was prepared in 36% yield from the reaction of [Ni(cod)(PMe3)2] with thiophosgene in toluene at 78 C and characterized by an X-ray analysis <1998AG2385>. PMe3

S Ni

Me3P

Ni

Cl

Cl PMe3

115

6.11.3.2.5

Compounds with the SCPMnRe core

The complexes with the SCPMnR core were prepared according to Scheme 35. Thus, Na2[MnRe(CO)6(S2CPR3)] (R = Pri, Cy) reacts with MeI in THF to give 116 and with Pt(cod)Cl2 to produce 117 with a dimetallacyclopentadienyl ring in 53% yield. Addition of PEt3 to 116 generates the complex 118 in 82% yield <2002AG3034>. [MnRe(CO)6(S2CPR3)]2–

PR3

PR3

S S (OC)3Re

Mn(CO)3

(cod)Pt

S PR3 S

116

Et3P(OC)2Re

Mn(CO)3 C O

118 a, R = Pri, b, R = Cy

Scheme 35

S Mn (CO)3 117

Re(CO)3

346 6.11.3.2.6

Functions Containing Two or One Chalcogens (and No Halogens) Compounds with the SCSi3 core

New compounds with this core are collected in Schemes 36 and 37. The Si-methylated hexasilabicyclo[2,2,2]octane 119 was prepared in 62% yield from the monolithio derivative (obtained from the H derivative and the superbase BuLi/ButOK) and (PhS)2 in THF at 42 C (Scheme 36) <2000JOM(611)12>. (Me3Si)3CSO2Li 120 was obtained from the reaction between (Me3Si)3CLi (from (Me3Si)3CH and MeLi in ether/THF) and SO2 at 78 C; addition of Cl2 at this temperature yields (Me3Si)3CSO2Cl 121 in 71% yield (m.p. 131 C) <2000CJC1642>.

Si

Si

Si

Si

BuLi, (PhS)2

Si

Si

Si

Si

Si

Si

Si PhS

H

Si

Si = SiMe3

119

Scheme 36

LiO2S

SiMe3

Me3Si

SiMe3

ClO2S

SiMe3

Me3Si

SiMe3

120

121

The starting compound for a series of complexes is LiSC(SiMe3)3 (see chapter 6.11.3.2.2 in COFGT (1995)), which exists in a tetrameric form in hexane consisting of an Li4S4 cubane skeleton. A further complex was obtained by the reaction with YbCl3 in the presence of TMEDA generating [Li(TMEDA)][YbCl3{SC(SiMe3)3(TMEDA)}] 122; both compounds were characterized by an X-ray analysis and the anion is shown in Scheme 37 <1995KID(26)242>.

S Li S

Li

Me2 N Cl

Li S

YbCl3 S

Li

TMEDA

S = SC(SiMe3)3

SiMe3 S

Yb

SiMe3 SiMe3

N Cl Cl Me2

122

Scheme 37

6.11.3.2.7

Compounds with the SCSi2P core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.3).

6.11.3.2.8

Compounds with the SCPSiLi core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.4).

Functions Containing Two or One Chalcogens (and No Halogens) 6.11.3.2.9

347

Compounds with the SCSi2Li core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.5).

6.11.3.2.10

Compounds with the SCN2Fe core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.6).

6.11.3.2.11

Compounds with the SCNSnPt core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.7).

6.11.3.2.12

Compounds with the SCSiSnLi core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.8).

6.11.3.2.13

Compounds with the SCFe3 core

The reaction of the in situ generated radical complex [Fe2(-CSR)(-CO)(CO)2Cp2] with [Fe2(CO)4Cp2] under UV photolysis leads to the novel 3-carbyne complex 123 (a, R = Me; b, R = Et) in 30% yield; the methyl derivative was characterized by an X-ray analysis. Alkylation of this complex with MeSO3CF3 afforded the cationic complex 124, as shown in Scheme 38; all CO groups are bridging ones <1993G703>.

R

Me

S

Me S +

MeSO3CF3 FeCp(CO)

(OC)CpFe

FeCp(CO)

(OC)CpFe

FeCp(CO)

FeCp(CO)

123

124

Scheme 38

6.11.3.2.14

Compounds with the SCRu3 core

The cluster 125 was obtained in 63% yield by stirring a solution of the complex [Ru3(CO)4(-PCy2)(-dppm)] in CS2 for 2 days. The cluster was characterized by an X-ray analysis <2002ZAAC2247>.

348

Functions Containing Two or One Chalcogens (and No Halogens) X S S

S

S Cy2P

Ru

Ru Cy2P

Ru S

PPh2

H (OC)3Os H

P Ph2

125

6.11.3.2.15

Os(CO)3 Os(CO)3 126

Compounds with the SCOs3 core

The neutral clusters 126 (X = CH2, S) were synthesized in 50% yield by the reaction of the corresponding Cl-cluster Os3H3(CO)9CCl with 1 equiv. of DBU and a 10-fold excess of thiane or 1,4-dithiane <1995JCS(D)2735>.

6.11.3.2.16

Compounds with the SCCo3 core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.10).

6.11.3.2.17

Compounds with the SCAu3 core

The only known complex with the SCAu3 core was obtained by the reaction of [Au(acac)PPh3] with [Me3SO]ClO4, which generated the trinuclear cationic Au complex 127 <1996JA699>. O S +

AuPPh3

Ph3PAu

AuPPh3 127

6.11.3.2.18

Compounds with the SCFe2Co core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.11).

6.11.3.2.19

Compounds with the SCFeCo2 core

A series of cationic compounds (128a–128h) was prepared in 70% to 80% yields by alkylation of the corresponding 3-CS complex (L = PPh3, P(OMe)3, or P(OPh)3) with the appropriate RX salt (Scheme 39, Table 5); the crystal structure of 128a is reported <1998JOM(551)139>. The complex 129 was obtained according to Scheme 40 in 75% yield in refluxing CS2 (12 h) <1998CC1577>.

349

Functions Containing Two or One Chalcogens (and No Halogens) S

SR

+

CO Fe

RX

CO

CpCo CoCp

CO Fe

CO

CpCo

L

CoCp

S

X–

L

S 128a–h

Scheme 39 Table 5 R, L, and X for the compounds 128a–128h Nr 128 a b c d e f g h

L

R

X

PPh3 PPh3 PPh3 PPh3 P(OPh)3 P(OPh)3 P(OMe)3 P(OMe)3

Me Et Allyl HgCl Me Et Me Et

SO3CF3 I I HgCl BPh4 BPh4 BPh4 BPh4

S S

S CO Fe

CpCo CoCp

S CS2

CO

Fe CpCo

PPh3

CoCp

S

CO PPh3

S 129

Scheme 40

6.11.3.2.20

Compounds with the SCCo2W core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.2.12).

6.11.3.3

Methanes Bearing One Selenium or One Tellurium Function and Three Functions Derived from the Group V (15) Element, Metalloid, and/or a Metal

The compounds bearing the SeC or TeC unit, with few exceptions, are restricted to examples with the SiMe3 group and the resulting trimethylsilylmethyl group (Me3Si)3C is generally abbreviated as TSi.

6.11.3.3.1

Compounds with the SeCN3 core

No further advances have occurred in this area since the publication of COFGT (1995) (chapter 6.11.3.3.1).

350 6.11.3.3.2

Functions Containing Two or One Chalcogens (and No Halogens) Compounds with the SeCSi3 core

This section contains compounds of the general type (Me3Si)3CSeX(TsiX) in which the Se atom is further bonded to other groups including transition metals. Reaction of TsiSeI with the corresponding thiocarbonyl derivatives (a, R = Me; b, R = Prn) in toluene forms the compounds 130 in 85% yield, as shown in Scheme 41 <2001AG2486>. If the compound TsiSeLi(DME) was treated with InCl3 in hexane, the compound (TsiSe)3In was formed in 31% yield and characterized by an X-ray analysis <1995IC4854>. Treatment of TsiSeLi(DME) with CuCl (in DME solution) or Cu(PCy3)2BF4 (in ether) leads to the complexes CuSeTsi (31% yield) and Cu(PCy3)SeTsi (35% yield), respectively; Cu(PCy3)SeTsi is dimeric with an SeCuSeCu four-membered ring and characterized by an X-ray analysis. The similar reaction with AgNO3 or AgBr(PCy3)2 produced the complexes AgSeTsi (56% yield) and Ag(PCy3)SeTsi (30% yield), respectively. The first one is tetrameric with an AgSeAgSeAgSeAgSe eightmembered ring and also characterized by an X-ray analysis. If the reaction with CuCl was carried out in benzene, the salt [Li(DME)2]{Cu[SeTsi]2} was obtained in 23% yield <1994IC1797>. O TSi

Se

I

O

HN +

N

S

TSi HN R Me3Si Me3Si Me3Si

Se

S

130 HN R

Se = SeTSi

Scheme 41

6.11.3.3.3

Compounds with the TeCSi3 core

Most of the compounds that have been described with the SeCSi3 core are also known with the TeCSi3 core and similarly to the selenium derivatives, only compounds with the SiMe3 group are known. Thus, compounds of the general type (Me3Si)3CTeX in which the Te atom is further bonded to other groups including transition metals have been prepared by the same working groups as reported for the corresponding selenium compounds. The (Me3Si)3C group is abbreviated as Tsi. A solution of (THF)LiTeC(SiMe3)3 in toluene was added to a solution of Cu(PCy3)BF4 to produce the complex Cu(TeTsi)PCy3 in 51% yield; see also compounds with the SeCSi3 core <1994IC1797>.

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Benneche, Synth. Commun. 1998, 28, 1415–1419. 1999BJ(337)373 R. Gordon-Week, S. Parmar, T. G. E. Davies, R. A. Leigh, Biochem. J. 1999, 337, 373–377. 1999T11903 D. P. M. Pleynet, J. K. Dutton, A. P. Johnson, Tetrahedron 1999, 55, 11903–11926. 1999CC499 R. Streubel, C. Neumann, Chem. Commun. 1999, 499–500. 1999AX1877 A. Linden, E. M. A. H. Awad, H. Heimgartner, Acta Cryst. 1999, C55, 1877–1881. 1999OM490 E. M. Lopez, D. Miguel, J. Perez, V. Riera, C. Bois, Y. Jeannin, Organometallics 1999, 18, 490–494. 1999OM1882 V. Cadierno, M. Zablocka, B. Donnadieu, A. Igau, J.-P. Majoral, Organometallics 1999, 18, 1882–1886. 1999CJC1340 A. D. Bain, P. Hazendonk, P. Couture, Can. J. Chem. 1999, 77, 1340–1348. 1999EJOC49 A. Romieu, D. Gasparutto, D. Molko, J.-L. Ravanat, J. Cadet, Eur. J. Org. Chem. 1999, 49–56. 1999EJIC2277 H. Braunschweig, C. Kollan, M. Coster, U. Englert, M. Mu¨ller, Eur. J. Inorg. Chem. 1999, 2277–2281. 1999RCB(48)2136 S. M. Bakunova, I. A. Grigorev, I. A. Kirilyuk, L. B. 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Functions Containing Two or One Chalcogens (and No Halogens) J. F. King, K. M. Baines, M. R. Netherton, V. Dave, Can. J. Chem. 2000, 78, 1642–1646. W. Hanefeld, S. Wurtz, J. Prakt. Chem. 2000, 342, 554–562. A. Arcadi, O. A. Attanasi, B. Guidi, E. Rossi, S. Santeusanio, Synlett 2000, 10, 1464–1466. K. Kluve, K.-H. Thiele, A. Sorkau, A. Sisak, B. Neumu¨ller, J. Organomet. Chem. 2000, 604, 68–71. A. Degl’Innocenti, A. Capperucci, J. Org. Chem. 2000, 65, 9206–9209. R. Johannesen, T. Benneche, J. Chem. Soc., Perkin Trans. 1 2000, 2677–2679. W. Kla¨ui, M. Berghahn, G. Reinwald, H. Lang, Angew. Chem., Int. Ed. Engl. 2000, 39, 2464–2466. C. M. Szabo, E. Oldfield, Biochim. Biophys. Res. Commun. 2001, 287, 468–473. O. I. Andreeva, E. V. Efimtseva, N. S. Padyukova, S. N. Kochetkov, S. N. Mikhailov, H. B. F. Dixon, M. Ya. Karpeisky, Mol. Biol. 2001, 35, 717–729. W. Kla¨ui, D. Schramm, W. Peters, Eur. J. Inorg. Chem. 2001, 3113–3117. W. Kla¨ui, D. Schramm, W. Peters, G. Reinwald, H. Lang, Eur. J. Inorg. Chem. 2001, 1415–1424. M. Mu¨ller, E. Lork, R. Mews, Angew. Chem., Int. Ed. Engl. 2001, 40, 1247–1249. W. W. du Mont, G. Mugesh, C. Wismach, P. G. Jones, Angew. Chem., Int. Ed. Engl. 2001, 40, 2486–2489. G. G. Furin, Yu. V. Gatilov, I. Yu. Bagryanskaya, E. L. Zhuzhgov, Russ. Chem. Bull. 2001, 50, 476–479. S. M. Bakunova, I. A. Kirilyuk, I. A. Gregorev, Russ. Chem. Bull. 2001, 50, 882–889. O. Tsuge, T. Hatta, H. Tashiro, H. Maeda, Heterocycles 2001, 55, 243–248. V. G. Albano, S. Bordoni, L. Busetto, A. Palazzi, P. Sabatino, V. Zanotti, J. Organomet. Chem. 2002, 659, 15–21. B. Galan, D. Miguel, J. Perez, V. Riera, Organometallics 2002, 21, 2979–2985. P. Pa¨tzold, J. Kiesgen, S. Luckert, T. Spaniol, U. Englert, Z. Anorg. Allg. Chem. 2002, 628, 1631–1635. P. Kang, C. S. Foote, J. Am. Chem. Soc. 2002, 124, 9629–9638. D. Miguel, D. Morales, V. Riera, S. Garcia-Granda, Angew. Chem., Int. Ed. Engl. 2002, 41, 3034–3035. J. M. Huang, H. Chen, R. Y. Chen, Chin. Chem. Lett. 2002, 13, 125–128. H.-C. Bo¨ttcher, M. Fernandez, M. Graf, K. Merzweiler, C. Wagner, Z. Anorg. Allg. Chem. 2002, 628, 2247–2248. D. V. Fomitchev, C. C. McLauchlan, R. H. Holm, Inorg. Chem. 2002, 41, 958–966. C. Santini, M. Pellei, G. G. Lobbia, D. Fedeli, G. Falcioni, J. Inorg. Biochem. 2003, 94, 348–354.

Functions Containing Two or One Chalcogens (and No Halogens)

353

Biographical sketch

Wolfgang Petz was born in Munich. He studied at the University of Munich, where he obtained his diploma in 1966 and his Ph.D. at the University of Marburg in 1969 under the direction of Professor Heinrich No¨th. After 2 years as scientific assistant he was appointed to Dozent auf Zeit at the University of Marburg, where he finished his Habilitation in 1979. In 1982 he moved to the Gmelin Institut of the Max-Planck-Society where he was author and editor of many organometallic volumes and in 1990 he became chief editor of the organometallic division. After closure of the Gmelin Institut in 1998 he moved to the MPI for Bioinorganic Chemistry in Mu¨lheim and took up his present position as apl. Professor at the University of Marburg. His scientific interests are on the field of organometallic chemistry, in particular carbene, difluorocarbene, and thiocarbonyl compounds including carbanion chemistry of transition metal carbonyl compounds.

Frank Weller was born in Stuttgart, Germany. He studied at the local University and got his Diploma in 1968. Having worked out a doctoral thesis with Professor K. Dehnicke in Marburg, Germany by 1971, he stayed there, and did some work mainly in the fields of vibrational spectroscopy and, later on, crystallography. Except for his early stage, when he was dealing with methylmercuric species, his scientific interests were, according to his mainly methodic activities, spread over a wide range of fields.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 317–353

6.12 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) S. SABA and J. A. CIACCIO Fordham University, New York, NY, USA 6.12.1 METHANES BEARING FOUR GROUP 15 ELEMENTS 6.12.1.1 Four Similar Group 15 Element Functions 6.12.1.1.1 Four nitrogen functions 6.12.1.1.2 Four phosphorus functions 6.12.1.2 Three Similar and One Different Group 15 Element Functions 6.12.1.2.1 Three arsenic functions 6.12.1.3 Two Similar and Two Different Group 15 Element Functions 6.12.2 METHANES BEARING THREE GROUP 15 ELEMENTS AND A METALLOID OR A METAL FUNCTION 6.12.2.1 Three Similar Group 15 Elements 6.12.2.1.1 Three nitrogen functions 6.12.2.1.2 Three phosphorus functions 6.12.3 METHANES BEARING TWO GROUP 15 ELEMENTS AND METALLOID AND/OR METAL FUNCTIONS 6.12.3.1 Two Similar Group 15 Elements 6.12.3.1.1 Two nitrogen functions 6.12.3.1.2 Two phosphorus functions 6.12.3.1.3 One phosphorus, two silicon, and one arsenic functions 6.12.4 METHANES BEARING ONE GROUP 15 ELEMENT AND METALLOID AND/OR METAL FUNCTIONS 6.12.4.1 Nitrogen Functions 6.12.4.1.1 One nitrogen and three boron functions 6.12.4.1.2 One nitrogen and three silicon functions 6.12.4.1.3 One nitrogen, two silicon, and one metal functions 6.12.4.1.4 One nitrogen and three metal functions 6.12.4.2 Phosphorus Functions 6.12.4.2.1 One phosphorus and three metalloid functions 6.12.4.2.2 One phosphorus and three metal functions 6.12.4.2.3 One phosphorus, one silicon, and two metal functions

355

356 356 356 358 359 359 359 359 359 360 360 360 360 360 361 366 367 367 367 367 369 369 372 372 374 376

356 6.12.1

Functions Containing at Least One Group 15 Element METHANES BEARING FOUR GROUP 15 ELEMENTS

6.12.1.1 6.12.1.1.1

Four Similar Group 15 Element Functions Four nitrogen functions

Several reasonably general methods for the construction of molecules bearing this function have been previously described <1995COFGT(12)359>. These include (i) nucleophilic exchange of chlorine atoms with amine functions, (ii) addition of amine functions to carbon–nitrogen double bonds, (iii) addition of nitrogen-bearing carbons to nitrogen–nitrogen double bonds, and (iv) exchange of a nitrogen-bearing group with a nitrogen-bearing carbanion. A few cyclic and acyclic compounds featuring four nitrogen functions have been reported since 1995. These include structures with two, three, or four similar nitrogen functions. While some of these compounds were prepared by adaptation of previously developed methods, a few were generated by miscellaneous syntheses. These preparations are described below.

(i) By nucleophilic exchange of chlorine atoms (a) From tetraalkylchloroformamidinium chlorides. A few tetrakis(dialkylamino)methanes were synthesized by adaptation of the method previously described for preparation of tetrakis(dimethylamino)methane from reaction of a tetraalkylchloroformadinium chloride with lithium dialkylamides (Equation (1) and Table 1); yields were low to moderate. Single-crystal structural studies on tetrakis(dimethylamino)methane and tetra(pyrrolidinyl)methane, as well as reactivity studies on hydrolysis of the former compound, have also been reported <1997CB(130)1739>. +

R2N Cl

2 LiNR2

Cl–

R2N

R2N

NR2 NR2 NR2

ð1Þ

Table 1 Nucleophilic exchange of chlorine and addition of dialkylamides R

Yield (%)

References

54 25 49 12

<1997CB(130)1739> <1997CB(130)1739> <1997CB(130)1739> <1997CB(130)1739>

Me Et (CH2)4 (CH2)5

(b) From pentacarbonyl(trichloromethylisocyanide)chromium(0). Reaction of pentacarbonyl(trichloromethylisocyanide)chromium(0) with imidazole afforded a 70% yield of the electron-deficient isocyanide complex pentacarbonyl[tris(imidazol-1-yl)methylisocyanide]chromium(0) (Equation (2)) <1995JOM(489)27>. N (OC)5Cr

C N CCl3 + N

N H

CH2Cl2, rt, 6 h 70%

N (OC)5Cr

C N

N N

N

ð2Þ

N

(ii) By nucleophilic addition to guanidinium salts N,N,N0 ,N0 ,N00 ,N00 -Hexamethylguanidinium chloride, when reacted with sodium hydride/dimethylamine in the presence of trimethyl borate, produced a mixture of tetrakis(dimethylamino)methane and tri(dimethylamino)orthoformamide (Equation (3)). The reaction was conducted in anhydrous THF affording, after crystallization from acetonitrile, colorless crystals of tetrakis(dimethylamino)methane in 11% yield <2000JPR(342)256>.

357

Functions Containing at Least One Group 15 Element +

Me2N NMe2 Me2N

NaH, HNMe2, B(OMe)3

Cl–

Me2N

THF, 11%

NMe2 NMe2 NMe2

+

NMe2 NMe2 NMe2

H

ð3Þ

Similarly, as part of a general preparative scheme for selective N-monoalkylation and 1,4N,N-dialkylation of 1,4,7,10-tetraazacyclododecane, 1, octahydro-2a,4a,6a,8a-tetraazapentaleno[1,6-cd]pentalene, 3, was obtained in higher than 95% yield from guanidinium chloride 2 upon reaction with 1M NaOH at 20 C (Scheme 1). The reagents and reaction conditions for conversion of 3 to its N-monoalkyl and 1,4-N,N-dialkyl derivatives were also reported <1998ACS1247>.

NH HN NH HN

i. 37% HCl EtOH, 20 °C

NH +

N

ii. C(OEt)4 EtOH, 78 °C, 19 h

N

N

1

Cl–

1M NaOH 20 °C, 1 h

2

N

N

N

N 3

Scheme 1

(iii) Miscellaneous syntheses A few isolated reactions leading to methanes bearing four nitrogen functions have also appeared in the literature since 1995. (a) The high activation of the CF bond in the anions of salts 4 and 5 was utilized in the interaction of these salts with silylated azoles. Tetrapyrrolemethane was prepared in 90% yield by treatment of salts 4 and 5 with trimethylsilylpyrrole. Salt 4 reacted readily at 10 C while salt 5 required 24 h at room temperature (Equations (4) and (5)) <2001AG(E)1247>. [CF3S(NMe2)2]+ [CF3S]–

+ 4

N TMS

N

4

[(Me2N)2CC(NMe2)2]2+ [CF3S– ]2 + 8

2

N TMS

C + 3TMSF + . . . 4

N

C + 6TMSF + . . . 4

ð4Þ

ð5Þ

5

(b) An NMR and GC-MS study of thermolysis fragments from the 1:1 adduct obtained by reaction of diisopropylcyanamide and trifluoroacetic anhydride led to detection of a compound with mass 431. The structure suggested for this compound was that for 4-(diisopropylamino)4-(trifluoroacetoxy)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 6. Another compound produced from reaction of compound 6 and N,N-diisopropyl-N0 ,N0 -bis(trifluoroacetyl)urea, 7, had a mass of 418 and was characterized as 4,4-bis(diisopropylamino)-2,6-bis(trifluoromethyl)-4H1,3,5-oxadiazine, 8 (Equation (6)). The former compound is the principal component in the original adduct <1997JOC9070>; however, the expected by-product shown in Equation (6) was never detected. (Pri)2N N F3C

OCOCF3 O N + (Pri)2N C N(COCF3)2 O CF3 6

7

(Pri)2N N F3C

N(Pri)2 N O

CF3

O O + F3C C O C N(COCF3)2

ð6Þ

8

(c) Tetrapyrazolylmethane (Cpz4) was used for the synthesis of the binuclear adduct [{CpMo(CO)2}(-Cpz4){Re(Cl)O3}][BF4] (81% yield) formed between the high oxidation state rhenium complex ClReO3 and a molybdenum-based organometallic ligand bearing a bridge with nitrogen donors like Cpz4 <1998POL1091>.

358

Functions Containing at Least One Group 15 Element

(d) In a study of some properties of N-polynitromethyl derivatives of fused benzotriazoles, 2,6bis(trinitromethyl)benzo[1,2-d;4,5-d0 ]ditriazole-4,8-dione, 11, was prepared by nitration of 2,6-bis(dinitromethyl)benzo[1,2-d;4,5-d0 ]ditriazole-4,8-dione, 9, and its sodium or potassium salts, 10, with conc. HNO3 (Scheme 2). Treatment of 11 with hydroxylamine afforded a chemically unstable dioxime that gradually decomposed to 11 <1993IZV1623>. O

O N

N

(NO2)2HC N

HNO3

N CH(NO2)2 N

O 9 M = Na+, K+

N

N

N

(NO2)3C N

60 °C , 24 h 44%

N

N

N C(NO2)3 O 11

MOAc O

HNO3

N

N

N

N

(NO2)2MC N

N CM(NO2)2 O 10

Scheme 2

(e) Nucleophilic displacement of a nitro group with an azido group was shown to occur in polynitromethanes. It was found that reaction of tetranitromethane with NaN3 in DMSO-CH2Cl2 afforded azidotrinitromethane in 20–24% yield (Equation (7)). When this reaction was carried out in pure DMSO or DMF, the yields were 10–14%. In aqueous acetone, this reaction produced a mixture of azidotrinitromethane and diazidodinitromethane (identified by GLC) that were difficult to separate. Pure diazidodinitromethane was obtained in 12% yield by the reaction of teranitromethane with excess NaN3 in aqueous ethanol at 5–10 C. Diazidodinitromethane was also detected by GLC in the reaction of the monoazide with NaN3 in aqueous ethanol <1997IZV338>. NaN3

C(NO2)4

ð7Þ

C(NO2)3N3

20–24%

(f) In the course of syntheses of condensed pyrazolo derivatives, reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitrile, 12, with dicyandiamide in refluxing ethanol afforded compounds for which Structure 13 was suggested (Equation (8)) <1997CCA1039>. These structures were based on spectral and elemental analyses of the products; however, only MS data for compound 13 (Ar = C6H4CH3m) were reported. NC ArHN

NH2 N

NH

NH2 +

NC N

12

NH2

NC

NH2

EtOH, 78 °C, 4 h 65–70%

ArHN

N

N

CN NH NH2 NH2

ð8Þ

13

Ar = C 6H4-CH3-m Ar = C 6H4-F-p

6.12.1.1.2

Four phosphorus functions

Only two reports describing the preparation of compounds of this class have appeared in the literature since 1995. Treatment of bis(trimethylsilyl)methylidene triphenylphosphorane, 14, with a phosphorus trihalide gave the corresponding dihalophosphanyl ylides, 15, which self-condensed in pyridine (X = Cl) or a mixture of benzene and pyridine (X = Br) to selectively afford tetramers having cations with a tetraphosphabicyclo[2.2.2]octane (1,3,5,7-tetraphosphabarrelane) structure, 16 (Scheme 3) <1995AG(E)1853>. The chloride salt was formed as a complex with pyridine in 43% yield; no yield was reported for the bromide salt. Reaction of the tetraphosphabarrelane chloride with either aluminum trichloride or gallium trichloride converted the singly charged

359

Functions Containing at Least One Group 15 Element

cation to a tetracation having a cubane structure (17; 20% yield for M = Al, and 50% yield for M = Ga), whereas treatment with antimony pentachloride afforded a mixture of dications, one with the barrelane structure preserved, 18, and a minor amount of a dication with a tetraphosphabicyclo[3.3.0]octane structure <1998ZN(B)1285>. (MCl4– )4 PPh3 MCl3

PPh3 Ph3P C(TMS)2

PX3 (–TMSX)

14

TMS

Ph3P

X = Cl, Br

X Ph3P

PX2

PP

PPP Ph3P

16

PPh P PPh3 3 17

PPh3

X P P X Ph3P X–

15

CH2Cl2

PPh3 SbCl5 X = Cl

Cl Cl PPh3 Ph3P P P Cl P P Cl Ph3P 2– SbCl5 18

Scheme 3

6.12.1.2

Three Similar and One Different Group 15 Element Functions

6.12.1.2.1

Three arsenic functions

In a reaction analogous to the synthesis of a 1,3,5,7-tetraphosphabarrelane cation described in Section 6.12.1.1.2, treatment of 14 with arsenic trichloride afforded a 1,3,5,7-tetraarsabarrelane cation, 20, along with minor amounts of 1,3-diarsetane and 1,3,5-triarsinane cations (Scheme 4) <2000CEJ3531>. The reaction proceeded via the intermediacy of a dichloroarsanyl trimethylsilyl ylide, 19 that tetramerized to 20 over a period of weeks. X-ray analysis of the crystalline cation 20 disclosed average AsCl bond lengths of 249 pm, reported to be by far the longest to be observed at a three-coordinate, pyramidal arsenic atom. PPh3 Ph3P C(TMS)2

AsCl3, Pyr

Cl As Ph3P As

TMS Ph3P

AsCl2

(–TMSCl ) 14

19

62%

Cl

PPh3

As As Cl Ph3P AsCl4– 20

Scheme 4

6.12.1.3

Two Similar and Two Different Group 15 Element Functions

No further advances have occurred in this area since the publication of chapter 6.12.1.3 in <1995COFGT(12)359>.

6.12.2

6.12.2.1

METHANES BEARING THREE GROUP 15 ELEMENTS AND A METALLOID OR A METAL FUNCTION Three Similar Group 15 Elements

Two reports have appeared in the literature since 1995 featuring compounds of this class; each describing structures containing a carbon that bears one metal function and either three nitrogen or three phosphorus functions.

360

Functions Containing at Least One Group 15 Element

6.12.2.1.1

Three nitrogen functions

In the course of studies on preparation of anionic tris(3,5-dimethylpyrazolyl)-containing ligands in transition metal chemistry, it was stated that deprotonation of HC(Me2Pz)3 (Pz = pyrazolyl) occurred cleanly without prior complexation to a metal center by reaction with MeLi in THF to form LiC(Me2Pz)3 in quantitative yield. The use of this compound as a reagent was established toward the preparation of a titanium-containing zwitterionic complex displaying a naked sp3-hybridized carbanion <2001CC705>.

6.12.2.1.2

Three phosphorus functions

Treatment of tris(diphenylphosphanyl)methane, 21, with an acetylacetonato (acac) gold(I) complex, 22, led to the formation of a neutral gold(I) complex, 23, with the gold atom linearly bound to both triphenylphosphine and the carbon of the methanide ligand, an unprecedented coordination type for tris(phosphanoyl)methanide and its derivatives (Equation (9)) <1996CB585>.

CH[PPh2(O)]3

+

Ph3P Au

Au(acac)PPh3 79%

21

6.12.3

23

22

PPh2O PPh2O PPh2O

+

acacH

ð9Þ

METHANES BEARING TWO GROUP 15 ELEMENTS AND METALLOID AND/OR METAL FUNCTIONS

6.12.3.1 6.12.3.1.1

Two Similar Group 15 Elements Two nitrogen functions

Only two compounds featuring a carbon attached to two nitrogen functions and two metal functions have been described since 1995. Both compounds exhibit carbene metal interactions and the nitrogens are part of five-membered heterocycles. Deprotonation of 3-borane-1,4,5-trimethylimidazole, 24, with BunLi afforded lithium 3-borane1,4,5-trimethylimidazol-2-ylidene, 25 (Equation (10)). An X-ray diffraction study on a single crystal of this salt grown from a THP solution at 4 C revealed dimeric units of two carbene anions connected by two lithium cations. The nitrogen-flanked carbene carbons have a shorter (2.169 A˚) and a longer (2.339 A˚) contact with the lithium cations <1998EJI843>.

-BH Me Me

-BH

3

N+

BunLi

N Me

THF-hexane, –40 °C

24

Me Me

N N Me

3

Li+

ð10Þ

25

The reaction of 2,6-bis(imidazolmethyl)pyridine, 26, and 1-methyl-2,5-bis(trimethylaminomethyl)pyrrole diiodide, 27, in nitromethane produced the cyclophane diiodide 28 (Equation (11)). Treatment of an aqueous solution of 28 with NH4PF6 afforded the dihexafluorophosphate salt which, upon deprotonation with Ag2O in DMSO at 55 C, afforded a dimeric silver N-heterocyclic carbene complex with composition [Ag4(28*)2][PF6]4, where 28* represents the deprotonated 28. Both the 13C NMR and X-ray diffraction data on the carbene complex indicated that each carbene is interacting with two different silver atoms via -bonding and -bonding interactions <2001CC1780>.

361

Functions Containing at Least One Group 15 Element + Me3N

N

N N

+

N

N + N

2I–

MeNO2

Me N

N

N

2I–

N + N

Me3N +

26

Me N

27

28

ð11Þ

N

N

Me N

N N

N 28*

6.12.3.1.2

Two phosphorus functions

(i) Two phosphorus and two silicon functions Only three practical syntheses of compounds of this class, all leading to the formation of diphosphirane functionality, have been reported since 1995. The first involved protonation of the lithium salt of a persilylated 2,3,4-triphosphapentadienide, 29, the first of its kind reported, leading to a bicyclic diphosphirane, 31 (no yield reported). The latter most likely arose from a valence isomerization of intermediate 30 (Scheme 5) <1996AG(E)313>.

TMS P Cl

+

2 LiP(TMS)2(THF)x

TMS

–LiCl –P(TMS)3

Li+(DME)3 TMS

P

P

TMS

TMS TMS

76%

58%

TMS

P

TMS P

P

Li+(DME)

TMS 3

29 H

H+ TMS TMS

TMS P

P

P

TMS

H TMS TMS

30

TMS P

P

TMS

P 31

Scheme 5

The same research group subsequently reported a reaction between dilithioferrocenylphosphanide and dichlorobis(trimethylsilanyl)methane, leading to a mixture of a diferrocenyldiphosphirane, 34 (65% yield), and a minor amount of a bis(methylene)phosphorane, 35. The authors explained the formation of these products by assuming an initial lithium–halogen exchange, affording a phosphenoid and carbenoid that immediately dimerized with elimination of LiCl; further reaction of the dimer with either the phosphenoid or carbenoid led to 34 and 35, respectively. The predominance of the diphosphorane suggests an increased stability of the phosphenoid compared to the carbenoid under these conditions (Scheme 6) <1997JOM(541)237>. The third report described a reaction between a 1,2-dihydro-1,2-phosphasilete, 36, and [bis(trimethylsilyl)methylene]chlorophosphane that led to a phosphaalkene-substituted phosphasilete, 37, in 93% yield, which then underwent a thermal isomerization to afford bicyclic diphosphirane 38 in 80% yield (Scheme 7) <1999CEJ1581>.

362

Functions Containing at Least One Group 15 Element PLi2 Fe

Cl +

Cl

PClLi

0 °C, ether

TMS

Fe

Li

TMS

+

TMS

Cl

TMS 33

32

TMS TMS –2 LiCl

P

P

TMS 32, –LiCl

Fe

Fe

TMS P

C(TMS)2

P +

C(TMS)2

Fe

65% 34

Fe

35

33, –LiCl

Scheme 6

But

Ph

TMS P Si TMS TMS

+

ClP

TMS –TMSCl TMS

93%

TMS

TMS

But

P P TMS Si TMS TMS

Ph

But

180 °C, 2 h

P P Ph Si TMS TMS

80%

37

36

TMS

38

Scheme 7

(ii) Two phosphorus and two metal functions A number of compounds of this class have been reported since 1995, the majority bearing two gold functions, in addition to a few compounds bearing two aluminum, chromium, lead, tin, or nickel functions. (a) Two phosphorus and two gold functions. All but one of the recently reported syntheses of compounds bearing two phosphorus and two gold functions involved carbon metallation by the use of basic acetylacetonato (acac) gold complexes, hydroxide, or hydride for deprotonation of a methylene or methine group bearing two phosphorus functions. The reaction of trinuclear gold complex 39 with a fourfold excess of [Au(acac)PPh3] gave heptanuclear gold complex 40 in which bis(diphenylphosphino)methanediide [bis(dppm)] bonds to four gold atoms as an eight-electron donor ligand (Equation (12)) <1995OM2918>. Ph3PAu AuPPh3 Ph2P (C6F5)3Au

PPh2 ClO4 Au Au(C6F5)3 4 [Au(acac)PPh3] PPh2 Ph2P CH2Cl2, 48 h, 80%

Ph2P (C6F5)3Au

PPh2 Au Au(C6F5)3 PPh2 Ph2P

Ph3PAu

ClO4

ð12Þ

AuPPh3

40

39

In a similar fashion, a cyclic, linearly coordinated tetranuclear gold complex 41 with tridentate bis(dppm) ligands was treated with 2 equiv. of [Au(PPh3)2]ClO4, leading to deprotonation of the CH groups and the formation of the hexanuclear complex 42 in 75% yield (Equation (13)) <1995CB121>. Ph3PAu AuPPh3

(acac)Au H Ph2P Au Ph2P

PPh2 Au PPh2

H Au(acac) 41

2 [Au(PPh3)2]ClO4, 8 h –2 acacH, 75%

Ph2P Au Ph2P

PPh2 Au PPh2

Ph3PAu AuPPh3 42

(ClO4)2

ð13Þ

363

Functions Containing at Least One Group 15 Element

With the aim of developing controlled syntheses of heterometallic species of high nuclearity, Ruiz and co-workers <1997OM3388> investigated the chemistry of bis(dppm) derivatives of ruthenium and manganese. Treatment of the bis(dppm) derivative 43 (M = Mn, L = CO) with one molar equivalent of [AuCl(PPh3)] and excess KOH gave a mixture of dinuclear and trinuclear, 44, complexes in a 6:4 molar ratio; however, the trinuclear, 44 (90% yield), tetranuclear, 45 (83% yield), and pentanuclear, 46 (81% yield), complexes were selectively obtained in the presence of excess KOH by treatment of the same bis(dppm) derivative with two, three, and four molar equivalents of [AuCl(PPh3)], respectively. By contrast, partial metallation of the bis(dppm) derivative, 43 (M = Ru and L = CNBut or CNPh), was not possible, and only the corresponding pentanuclear complex, 46, could be isolated in pure form (L = CNBut, 78% yield; L = CNPh, 81% yield) (Scheme 8 and Table 2).

2 [AuClPPh3]

Ph2 L P M P Ph L

Ph3PAu H

KOH, CH2Cl2

2

Ph2 AuPPh3 P H P Ph2

n

[AuClPPh3] KOH, CH2Cl2

44

Ph2 L P M P Ph2 L 43

Ph2 P P Ph2

Ph3PAu H

4 [AuClPPh3] KOH, CH2Cl2

Ph2 L P M P Ph L

Ph3PAu Ph3PAu

2

Ph2 L P M P Ph2 L 45

Ph2 P AuPPh3 P AuPPh3 Ph2

n

n Ph2 [AuClPPh3] P AuPPh3 P AuPPh3 KOH, CH2Cl2 Ph2

46

Scheme 8

Table 2 Controlled syntheses of heterometallic species of high nuclearity Compound

M

L

n

Yield (%)

References

44 45 46 46 46

Mn Mn Mn Ru Ru

CO CO CO CNBut CNPh

1+ 1+ 1+ 2+ 2+

90 83 81 78 81

<1997OM3388> <1997OM3388> <1997OM3388> <1997OM3388> <1997OM3388>

Treatment of bis(pentafluorophenyl)gold(III) methanide complex 47 (Scheme 9) and tris(pentafluorophenyl)gold(III) methanide complex 50 (Equation (14)) with [Au(acac)L] afforded the corresponding disubstituted products (80% [L = PPh3] and 74% [L = AsPh3] for the metallacycle 47; 71% [L = PPh3] for the acyclic compound). When complex 47 was treated sequentially with NaH and [Au(acac)PPh3] a four-membered methanide complex was afforded in 53% yield (Scheme 9) <1998POL2029>.

S C6F5 Au PPh2 C6F5 Ph3PAu PPh2 S 48

i. NaH ii. [Au(acac)PPh3] 53%

C6F5 S PPh2 ClO4 2 [Au(acac)L] Au C6F5 S PPh2 CH2Cl2, 2 h 47

Scheme 9

C6F5 C6F5

S PPh2 ClO4 AuL AuL S PPh2

Au

49

364

Functions Containing at Least One Group 15 Element (C6F5)3Au S PPh2

2 [Au(acac)]PPh3, CH2Cl2, 1 h 71%

Ph2P S

(C6F5)3Au S PPh2 AuPPh3 Ph2P AuPPh3 S

ð14Þ

50

In a report on the synthesis of a family of cyclic palladium complexes containing N,P-diphosphinomonoimine ligands, exposure to two molar equivalents of [Au(acac)PPh3] led to double deprotonation and functionalization of a palladium complex having an acidic methylene group (Equation (15)) <1998OM4544>.

Tol

N

Tol

Pd N

Ph3PAu AuPPh3 Ph2P

OTf

Ph2P PPh2

2 [Au(acac)PPh3], CH2Cl2, 36 h 88%

N

OTf

PPh2

Tol

N

Tol

Pd N N

ð15Þ

In another report detailing a synthesis of this class of compound by deprotonation and metallation of an acidic methylene or methine, gold ferrocenyl methanide derivative 52 was prepared in 86% yield when 51 was treated with [O(AuPPh3)3]ClO4 (Equation (16)) <1999ICA60>.

Fe

P Ph2

PPh2

(ClO4)2

Ph3PAu AuPPh3

ClO4 [O(AuPPh3)3]ClO4, CH2Cl2, 2 h

Fe

P Ph2

86%

51

PPh2 AuPPh3

ð16Þ

52

Finally, a dinuclear complex 53 with a carbon bearing two gold functions and two phosphorus functions was prepared in 70% yield from the reaction of the diylide C(PPh3)2 with AuCltetrahydrothiophene (tht) complex in a 1:2 molar ratio (Equation (17)) <2002OM5887>.

2 AuCl(tht)

C(PPh3)2, THF, 1 h 70%

Cl Au Au Cl

PPh3

ð17Þ

PPh3 53

(b) Two phosphorus and two aluminum functions. Since the mid-1990s, a notable amount of interest has focused on the development of nitrogen donor complexes as alternatives to cyclopentadienyl groups on metals, with impact on homogeneous catalysis. One study investigating bis(iminophosphorano)methane chemistry led to the synthesis of novel aluminum complex 55 (67% yield) by both single and double, stepwise deprotonation of the ligand’s methylene backbone (Scheme 10) <1999OM4241>. A patent also appeared that describes the preparation of derivatives of the aluminum complex with various groups attached to nitrogen, phosphorus, and aluminum, and it outlines processes for polymerizing various alkenes using the various complexes <1999USP6235919B1>.

Ph2P N Ph2P N

TMS AlMe3, PhMe, 20 °C 68% TMS

TMS Ph2P N Me Al Me Ph2P N TMS

AlMe3, PhMe, 120 °C

Ph2 Me2 Al P TMS N N TMS Al P Me2 Ph2 55

54 2 AlMe3, PhMe, 120 °C 67%

Scheme 10

365

Functions Containing at Least One Group 15 Element

(c) Two phosphorus and two tin, lead, or chromium functions. Disilylated bis(iminophosphorano)methane, 54, was reported to lead to 1,3-dimetallacyclobutanes (56–58) upon monodeprotonation with BunLi and treatment with PbCl2 <2001AG(E)2501> (Equation (18)), double deprotonation with BunLi and treatment with CrCl2(THF)2 (Equation (19)) <1999CC1993>, and direct treatment with M[N(TMS)2]2 (M = Sn, 70% yield; Pb, 80% yield, Equation (20)), <2001AG(E)2501>. TMS TMS Ph2P N

TMS Ph2P N

BunLi, THF

PbCl2, Et2O,18 h

Li Ph2P N

Ph2P N

TMS

54

84%

Ph2P

TMS N

Ph2P N

N Pb TMS

TMS

PPh2

Pb

PPh2

ð18Þ

N TMS

56 TMS

TMS Ph2P N Ph2P N

2 BunLi, THF

Li Li

Ph2P N Ph2P N

TMS

TMS CrCl2(THF)2, THF, 2 days

Ph2 Ph2 TMS N P P N Cr

56% TMS

TMS

54

Cr

N P P N TMS Ph2 Ph2

ð19Þ

57 TMS TMS Ph2P N Ph2P N

Ph2P

54

PPh2

M

M[N(TMS)2]2, PhMe, M = Pb, Sn TMS

TMS N

Ph2P N

N M TMS

ð20Þ

PPh2 N TMS

58 n

Double deprotonation of 54 with Bu Li and then treatment with 2 equiv. of CrCl2(THF)2 was reported to lead to partially substituted tetranuclear complex 59 (Equation (21)) <1999CC1993>. TMS N

TMS Ph2P N Ph2P N

i. 2 BunLi, THF; ii. 2 CrCl 2(THF)2 ,THF, 1 day 61% TMS

54

Cl Ph2P Cr Cl Li(THF)2 N TMS Ph2P Cr Cl Cr PPh2 Cl TMS N Cl PPh 2 (THF)2Li Cr Cl N TMS 59

ð21Þ

The dimetallacyclobutane 57 is the first example of a bridging chromium carbene without the usual carbonyl or cyclopentadienyl ligands, and it is also the first example of a chromium carbene complex that contains two phosphorus functions on the carbene carbon. (d) Two phosphorus and two nickel functions. In a study of oxidative addition reactions of dichlorophosphaalkene 60 with Ni(0) complexes, Konze and co-workers isolated the first example of a complex 61 (59–74% yield) with a mixed 2,4-diphosphaallene ligand that is bridged between two nickel atoms forming a fused, bicyclic heterocycle (Equation (22)) <1998OM1569>.

2 Ni(PPh3)2L + Cl2C=PN(TMS)2 60

PhMe, –50 °C to rt, 1 h

Cl Ph3P Ni

L = (C2H4), 74%; (COD), 69%; (PPh3)2, 59%

Cl Ni PPh3 P

PPh3

ð22Þ

(TMS)2N 61

Treatment of the bicyclic complex 61 with 2 equiv. of triethylphosphine at 40 C led to substitution of the PPh3 groups on nickel by PEt3, but the newly formed complex 62 was unstable and could not be isolated (Equation (23)).

366

Functions Containing at Least One Group 15 Element

61

3 PEt3, THF, –78 to –40 °C, 15 min

Cl Et3P Ni

Cl Ni PEt3 PPh3

P

Not isolated

ð23Þ

(TMS)2N 62

(iii) Two phosphorus, one metal, and one silicon functions In a study similar to that described in Section 6.12.3.1.2.(i).(c), Konze and co-workers <1998OM5275> treated dichlorophosphaalkene 60 with a Pd(0) complex and isolated the first example of a complex, 63, with a phosphinio-methylene(imino)metallophosphorane ligand 2-coordinated to one palladium center and 1-coordinated to another in a dinuclear complex (Equation (24)).

2Pd(PEt 3)4

+

60

Hexanes, 0 °C to rt, 15 min 57%

Et3P Cl Pd PEt3 Pd TMS P Et3P NTMS Cl

ð24Þ

63

Treatment of complex 63 with 3 equiv. of either iodomethane or sodium iodide afforded a similar complex, 64, in 24% yield. Hydrolysis of complex 63 afforded another novel, threemembered heterocycle, 65 (Scheme 11). TMS Cl Pd Et3P

PEt3

H2O, THF, rt, 5 min

P

82%

O NHTMS

3 MeI, THF, rt, 24 h 63

24%

Et3P I Pd PEt3 Pd P TMS Et3P NTMS I

65

64

Scheme 11

The only recent synthesis of a compound with a carbon bearing one phosphorus, one lithium, and one silicon function was that of the first coligand-free diphosphinomethanide, 67, afforded in crystalline form, by the reaction of silyl substituted phosphinomethane 66 with BunLi (Equation (25)) . The crystal structure of this trimeric compound showed each lithium atom surrounded by two phosphorus atoms and one carbon atom, with two of the lithium atoms displaying weak lithium–phenyl contacts. Me2P PhMe2Si Me2P

H

BunLi –BuH

1/3

66

6.12.3.1.3

Me2P PhMe2Si Me2P

Li

ð25Þ

3

67

One phosphorus, two silicon, and one arsenic functions

Only two compounds of this description were prepared recently; both are phosphaarsiranes. Treatment of metalloarsane (5-C5Me5)(CO2)FeAs(TMS)2, 68, with 1 equiv. of [bis(trimethylsilyl)methylene]chlorophosphane gave 1-metallo-1-arsa-2-phosphapropene 69 and a few crystals of dimetallophosphaarsirane 70 (Equation (26)) <1996CB219>.

+ ClP C(TMS)2 OC Fe OC As(TMS)2 68

C(TMS)2 [Fe]

THF, –15 °C to rt, overnight 69, 88%; 70, trace

OC Fe As P OC TMS

[Fe] = [(η 5-C5Me5)(CO)2Fe]

69

[Fe] P As

+

TMS

TMS 70

ð26Þ

367

Functions Containing at Least One Group 15 Element

The 1-arsa-2-phosphapropene 69 was treated with an excess of [(Z)-cyclooctene]Cr(CO)5 and the resulting product was purified by chromatography on Florisil followed by crystallization to afford crystalline phosphaarsirane 71 in 17% yield (Equation (27)). 69

i. [(Z )-cyclooctene]Cr(CO)5, n -pentane, 20 °C, 2 days; ii. SiO2/H2O

[Fe] As

TMS H P

17% TMS Cr(CO5)

ð27Þ

71

6.12.4

METHANES BEARING ONE GROUP 15 ELEMENT AND METALLOID AND/OR METAL FUNCTIONS

6.12.4.1 6.12.4.1.1

Nitrogen Functions One nitrogen and three boron functions

Since 1995, only one report has appeared that describes the preparation of compounds bearing nitrogen and three boron functions. By reacting sterically hindered isocyanide ButNC with [anti-B18H22] in benzene, cluster carbonatom insertion occurred yielding macropolyhedral carbaboranes [7-(ButMeHN)-(anti)-B18H20] and [9-(ButNH2)-(anti)-9-B17H19-8-(CN)] in 6% and 12% yields, respectively <1995CC2407>. These compounds were characterized by MS and NMR spectroscopy; the latter compound was further characterized by single-crystal X-ray diffraction analysis.

6.12.4.1.2

One nitrogen and three silicon functions

A few compounds with a carbon bearing nitrogen and three silicon functions have appeared since 1995. All feature trimethylsilyl substituents with the nitrogen as part of an isothiocyanate moiety or a heterocyclic system. As a promising building block for heterocyclic syntheses, tris(trimethylsilyl)methyl isothiocyanate was prepared in 95% yield by a novel, direct lithiation of methyl isothiocyanate at 95 C using LDA and trapping of the carbanion intermediate with excess TMSCl/THF (Equation (28)) <1997S423>. The product was characterized by its melting point as well as IR and 1H NMR spectra. MeN C S

+ 3TMSCl

LDA (3 equiv.) THF, Et2O, hexane, –95 °C

(TMS)3C N C S

ð28Þ

95%

As part of a synthetic exploration of the Peterson olefination route to 1-(1-alkenyl)benzotriazoles, 1-(trimethylsilylmethyl)benzotriazole, 72, was lithiated at the -carbon using LDA, and the resulting lithiated species was trapped with TMSCl affording 1-bis(trimethylsilyl)methyl-1H-benzotriazole, 73, in 83% yield (Scheme 12). Further treatment of the latter compound with LDA and trapping with TMSCl afforded 1-tris(trimethylsilyl)methyl-1H-benzotriazole, 74, and 4-trimethylsilyl-1-tris(trimethylsilyl)methyl-1H-benzotriazole, 75, as crystalline compounds in 44% and 41% yields, respectively. These compounds were characterized by elemental analysis and NMR spectroscopy (1H, 13C). While Peterson olefination on other silylated benzotriazole derivatives was carried out, no further exploration on compounds 74 and 75 was reported <1999T11903>. Photolysis of 1,3-bis(trimethylsilyldiazomethyl)-1,1,3,3-tetramethyl-2,2-diphenyltrisilane, 76, in cyclohexane with a high-pressure mercury lamp at 0 C afforded the five-membered heterocycle 79 in 11% yield (Scheme 13). The structure of this compound was established spectroscopically (1H, 13C, 29Si NMR) as well as by elemental analysis, exact mass determination by high-resolution mass spectrometry (HRMS), and X-ray crystallographic analysis. It was suggested that this heterocycle is the hydrolysis product of the bicyclic azo compound 78 produced from intramolecular [2+3]-cycloaddition of diazosilene 77. Photolysis of

368

Functions Containing at Least One Group 15 Element N N

LDA / TMSCl, –78 °C

N

83%

N

N

LDA / TMSCl, –78 °C

N

TMS

TMS

72

TMS 73

TMS

N

N

N N TMS

N

+

N

TMS TMS

TMS

74

TMS TMS 75

Scheme 12

TMS N2 TMS

Ph2 N2 Si Si Si TMS Me2 Me2

hν Cyclohexane, 4 h

Ph2Si Me2Si TMS

76

SiMe2 N

Me2(HO)Si

Ph2Si Me2Si

N 77

TMS N N TMS 78

H2O

TMS N HN

Me2 Si

[2 + 3]

SiMe2 TMS SiPh2

TMS H2O

SiMe2 TMS

N

N Me2Si SiPh2

79

Scheme 13

1,4-bis(dimethylphenylsilyldiazomethyl)-1,1,2,2,3,3,4,4-octamethyltetrasilane, 80, in cyclohexane afforded compound 82 in 25% yield, and is believed to have formed from nitrogen extrusion of the bicyclic azo compound 81 (Scheme 14) <1995JOM(499)99>.

N2 PhMe2Si

SiMe2Ph

N2 (SiMe2)4 80

hν

SiMe2Ph

Me2Si Me2Si Me2Si PhMe2Si

SiMe2 N

N

[2 + 3]

PhMe2Si Me2Si Me2Si

Me2 Si N

N Si Me2 SiHMe2Ph 81 –N2

Me2 Si SiMe2 Me2Si Si PhMe2Si Me2 82

PhMe2Si

Scheme 14

Silaethene Ph2Si¼C(TMS)2, 83, a product of thermal elimination of LiX (X = Br, F) from Ph2SiXCLi(TMS)2 and its rearranged form 84, produced upon interaction of 83 with LiBr, underwent [3 + 2]-cycloaddition with azidodi-t-butylmethylsilane as well as azidotri-t-butylsilane in diethyl ether at 78 C affording cycloadducts 85–87 (Scheme 15) <1995CB1231>.

369

Functions Containing at Least One Group 15 Element

Ph2Si

C(TMS)2

+ LiBr _

83 . LiBr

TMS Me2Si

83

+ LiBr _

TMS

. LiBr

Me2Si

SiMePh2

84

Bu3t SiN3

Bu2t MeSiN3

Ph2Si C(TMS)2 N N Bu2t MeSi N

SiMePh2

Bu3t SiN3

TMS Ph2Si SiMePh2 N N Bu3t Si N

Ph2Si C(TMS)2 N N Bu3t Si N

85

86

87

Scheme 15

6.12.4.1.3

One nitrogen, two silicon, and one metal functions

There is a single report of such a compound since 1995. [3+2]-Cycloaddition of the labile stannaethene 88 with But2MeSiN3 at 78 C afforded the triazoline cycloadduct 89 (Scheme 16) . This compound is a suitable source of the thermolabile stannaimine Me2Sn¼NSiBut2Me.

Me2Sn C(TMS)2 PhLi Br Br

TMS Me TMS Me Sn N N But2MeSi N 89

Bu2t MeSiN3 Me2Sn C(TMS)2 –LiBr Me2Sn C(TMS)2 Br Li –78 °C 88

Scheme 16

6.12.4.1.4

One nitrogen and three metal functions

(i) One nitrogen and three chromium functions There appears to be only one report of a compound belonging to this class since 1995. Cothermolysis of the thiocarbenoid complex CpCr(CO)2(SCNMe)2, 90, with [CpCr(CO)3]2 afforded a four-component mixture which, after column chromatography on silica gel, yielded a dark brown solid, Cp4Cr4S2(CO)(CNMe2), in 36% yield as a highly air-sensitive compound. This compound was characterized by 1H NMR and IR spectroscopy, MS, and single-crystal X-ray diffraction analysis revealing it as a 3-aminocarbyne cubane complex 91 (Equation (29)) <2002OM4408>. All six CrCr bonds in compound 91 are not shown for clarity. CO CO 2 OC Cr

O +

Toluene, 110 °C, 3 h Cr S OC OC 36% N Me H Me 90

Cr S

Cr

S

Cr

Cr

Me N Me

+ ...

ð29Þ

91

(ii) One nitrogen and three ruthenium functions Two reports on compounds bearing one nitrogen and three ruthenium functions have appeared since 1995. The organometallic cluster H3Ru3(CNMeBz)(CO)6(PPh3)3 was prepared in 77% yield by treatment of a cyclohexane solution of HRu3(CNMeBz)(CO)10 with PPh3 and heating the mixture in the presence of hydrogen gas bubbled through the solution. Chemical oxidation of this cluster with Ag+ or ferricenium produced the 47-electron cation [H3Ru3(CNMeBz)(CO)6(PPh3)3]1+ which was

370

Functions Containing at Least One Group 15 Element

characterized spectroscopically (EPR, 1H, 31P NMR, IR). An account of cyclic voltammetric experiments on this cluster has been detailed <1998OM872>. An investigation on the mechanistic decomposition of the 47-electron cationic cluster, generated by chemical or electrochemical oxidation of the 48-electron precursor, has also been reported. In connection with this study, several clusters featuring a tetracoordinated carbon bearing nitrogen and three ruthenium functions were prepared <2001JOM(633)51>. These included H3Ru3(CNMeBz)6L3 (L = PPh3, SbPh3), prepared by previously published procedures <1998OM872, 1990IS196>, and H3Ru3(CNEtBz)6(PPh3)3, H3Ru3(CNMeBz)6(PPh3)2(CNBz), prepared using analogous procedures by substitution of appropriate ligands on the parent carbonyls. No further preparative details were provided, but IR and 1H NMR data for the latter compounds were reported.

(iii) One nitrogen, two cobalt, and one iron functions A few compounds having this structural unit have been described since 1995. Clusters of the type 93 were generated upon cleavage of the 2-isothiocyanate ligand in [Fe(PPh3)2(CO)2(2-SCNR)], 92, by 2 equiv. of [Co(-Cp)(PPh3)2] (Equation (30)) <1999JOM(573)109>. While the cluster with R = MeC(O) decomposed during reaction work-up, others were obtained in good yields. R OC

PPh3 Fe

+ 2

S

OC PPh3

N

N R Benzene, 5 h

Co

65–70%

Co

Fe

Co Ph3P

PHPh3

S

92

CO CO

ð30Þ

PPh3

93 R = Ac, PhC(O), Me2N– C6H4–C(O)

Except when R = Me2NC6H4C(O), reaction of clusters 93 with CF3SO2OMe afforded salts 94 in which the CNFeCo2 moiety was retained. All the clusters were characterized by their IR and 1 H NMR spectra. The crystal structure of cluster 94 with R = PhC(CO) was also studied by X-ray diffraction analysis.

R + Me N Co Fe Co S

CO CO

PPh3

94

(iv) One nitrogen and three osmium functions Numerous reports describing the preparation, reactivity, and crystal structures of various triosmium clusters having a carbon bearing one nitrogen and three osmium functions have appeared in the literature since 1995. All clusters described contain a triosmium alkylidyne metal core linked to a nitrogen function at an apical position. Triosmium alkylidyne cluster 96 was synthesized by the reaction of 95 with 1 equiv. of DBU in the presence of a 10-fold excess of 4-vinylpyridine (Equation (31)) <1995MI311>. Treatment of cluster 96 with a slight excess of [Os3(CO)10(NMe)2] in refluxing n-hexane for 8 h produced the homonuclearly linked cluster 97 in 34% yield, while reaction of 96 in refluxing CH2Cl2 with traces of water, using stoichiometric amounts of Wilkinson’s catalyst RhCl(PPh3)3, afforded a 29% yield of 98 <1995JOM(493)229>.

371

Functions Containing at Least One Group 15 Element

Cl N

H

Os

H

CH2Cl2, 0 °C, 0.5 h 69%

Os

Os

ð31Þ

4-Vinylpyridine, DBU

H

H

Os

H Os

Os

95 96

Os Os

Os H

H

Me

H

N

N

H

Os

H

H

Os

H Os

Os

Os

Os

O

98

97

Following the same methodology as that used for the preparation of 96, reaction of 95 with pyridine-containing ligands 99, 100 <1995JCS(D)1379>, 101, 102 <1995ICA(234)5, 1995JCS(D)3995>, 103, 104 <1996JCS(D)1853>, 105 <1996JCS(D)2293>, 106, 107, and 108 <1999JOM(584)48> afforded moderate-to-good yields of structurally similar complexes.

N N Fe

N

99

N N

Fe

100

N

N

101

102

OC16H33

N

N

N

N

103

104

105

372

Functions Containing at Least One Group 15 Element

R

OMe O 2N

N

N

N

106

107

N 108

R = H, CMe3, NH2, NMe2, SMe, OMe, OC6H13, OC7H15, OC9H19, Br, Cl

Treatment of an ethereal solution of the triosmium cluster 109 with an excess of diazomethane afforded the diazomethylidyne complex 110 (Equation (32)). The structure of this compound was established based on its analytical and spectroscopic data and was further characterized by singlecrystal X-ray crystallography <2000OM5623>. Ph P

Ph

N

Os

CH2N2, Et2O

P Ph Os Ph

Os

Os

40%

ð32Þ

H

CH2Cl2, –10 °C, 1 h

H

P Ph Os Ph

Os H 110

109

6.12.4.2

Ph P

N

Phosphorus Functions

By far, the greatest number of reports since 1995 of compounds possessing a carbon bearing one phosphorus and three metalloid and/or metal functions is for those with one phosphorus and three silicon functions. A few examples have been reported of compounds with a carbon bearing one phosphorus and either three transition metals, or one silicon and two metal functions.

6.12.4.2.1

One phosphorus and three metalloid functions

(i) By nucleophilic exchange of chlorine atoms on a silicon atom Two equivalents of phosphinomethanide 111 reacted with various chlorosilanes generating phosphorus ylides 112 with a tetraheteroatom-substituted methane functionality . When the reaction was carried out in a 1:1 ratio where R = Ph and R0 = Cl, phosphorus ylide 112 was obtained in an impure form along with tetraheteroatom-substituted methane 113 resulting from monosubstitution on silicon (Equation (33)) <1995JOM(501)167>.

R Cl Si Cl + n {Li[C(PMe2)(TMS)2]}2.TMEDA R1

111

R1 R TMS Me2P Si P TMS + PhCl2Si TMS TMS Me Me 112

R = R1 = Me; R = R1 = Cl; R = Ph, R1 = Cl

PMe2 TMS TMS 113

ð33Þ

373

Functions Containing at Least One Group 15 Element (ii) By nucleophilic exchange of chlorine atoms on a phosphorus atom

Tris(trimethylsilyl)methyllithium was reported to effect nucleophilic displacement of chlorine on the phosphorus atoms of chloro-substituted iminophosphane 114 <1997CC293> and 1-chloro-1Hphosphirene 115 <1997CB711>, affording the corresponding products 116 and 117 in 76% and 90% yields, respectively (Scheme 17).

ClP N 114 THF, –78 °C, 76% TMS TMS TMS

TMS TMS

P N TMS 116

Li

But Cl

P TMS TMS TMS

115 Ph Et2O, 90%

But P Ph 117

Scheme 17

The first reports outlining the preparation of diphosphenes (TMS)3CP¼PC(TMS)3 <1982TL4941> and (2,4,6-But)C6H2P¼PC(TMS)3 <1983JA1655> by reductive coupling of the corresponding alkyldichlorophosphines appeared in the early 1980s, but more recent reports describe further transformations at the phosphorus–phosphorus double bond, including [2 + 1] cycloadditions with dichlorocarbene and isonitriles <1998JFC(89)73, 1999ZAAC1934>; each of these transformations left the tetrasubstituted carbon atom unchanged.

(iii) By reaction of carbon–phosphorus double bonds P-Halogeno-, P-phenyl-, and P-phosphanyl-substituted 2,2-bis(trimethylsilyl)-1-phosphaethenes, 118, have been reported to react with C¼P cleavage to afford compounds possessing a carbon bearing one phosphorus and three silicon functions, or a carbon bearing one phosphorus, one germanium, and two silicon functions. When a phosphanyl-substituted phosphaethene (118; X = (5-1,3-But2C5H3)(CO)2Fe P(TMS)) was treated with an excess of [(Z)-cyclooctene]Cr(CO)5, the 1,2-diphosphaferrocene pentacarbonylchromium adduct 121 was obtained in low yield along with the butterfly complex 119 and the metallodiphosphene 120, the latter two being too unstable to isolate and only identified by 31 P-NMR data in comparison with those of related compounds (Equation (34)) <1995CB665>.

XP C(TMS)2

118

LCr(CO)5

[Fe]

TMSO

P P C(TMS)3 + [Fe] + P P Cr C(TMS)3 (CO)4 But 119

120

OTMS OTMS P P Fe Cr(CO)5 But 121

ð34Þ

X = (η 5-1,3-Bu2t C5H3)(CO)2Fe–P(TMS) L = (Z )-cyclooctene [Fe] = (h5-1,3-Bu2t C5H3)(CO)2Fe

Treatment of P-halogenophosphaethenes (118; X = Cl, Br, I) with an equimolar amount of hexadichlorosilane effected C¼P cleavage and P¼P formation, giving diphosphene 122 in 71% yield when X = Cl . By following the reaction by 31P-NMR, the authors postulated the intermediacy of the phosphaalkene (TMS)2C¼PSiCl3, which then

374

Functions Containing at Least One Group 15 Element

dimerizes by 1,2-addition of the PSi bond of one molecule to the C¼P bond of another to give (TMS)2C¼P-P(SiCl3)C(TMS)2SiCl3, followed by a 1,2-trichlorosilyl shift from phosphorus to carbon, thereby affording diphosphene 122 (Equation (35)). Si2Cl6, hexanes, 60 °C, 8 days; X = Cl XP=C(TMS)2

Cl3Si(TMS)2C

71%

P P

C(TMS)2SiCl3

ð35Þ

122

118

In their studies of group 14 carbene analogs and their reactions with P-phosphanyl phosphaalkenes, du Mont and co-workers observed a similar type of transformation when phosphaethene 122 (X = PPri2) was converted to diphosphene 123 (83% yield) upon treatment with the silylene SiCl2; the latter was generated in situ by an -elimination of Me3GeCl from Me3GeSiCl3, induced by the dialkylphosphanyl group within phosphaethene 118 (Equation (36)) <2002AG(E)3829>. The same research group also investigated the reactivity of phosphaethene 118 (X = PPri2) with GeCl2-dioxane, observing the formation of diphosphene 124 by 31P-NMR and isolating a crystal suitable for low-temperature X-ray diffraction analysis; however, the major isolated product was the fused bicyclic heterocycle 125, which possesses two carbons that each bear one phosphorus, one germanium, and two silicon functions (50% yield) (Equation (37)) <2001MI609>. i

Me3GeSiCl3; X = PPr 2

Pr 2i P Cl2Si

XP=C(TMS)2 83% 118

(TMS)2C SiCl2 PPr 2i P P

ð36Þ

C(TMS)2 123

XP=C(TMS)2 118

GeCl2; X = PPr 2i –(Pr 2i P)2GeCl2

i (TMS)2C GeCl2PPr 2

P P Cl3Ge C(TMS)2

–Pr2i PCl 50%

124

Cl2Ge P C(TMS) 2 (TMS)2C P Ge Cl2 125

ð37Þ

In another recent study of the reaction of silylenes and germylenes with phosphaalkenes, Kimel et al. <2001MC85> described the reaction of phosphaethene 118 (X = Ph) with MMe2 (M = Si, Ge) affording the corresponding unstable phosphasilacyclopropane (126, M = Si) and phosphogermacyclopropane (126, M = Ge), respectively; the former generated as part of a gross mixture of other phosphorus-containing products and identified only by a 31P-NMR signal at 132.4; the latter obtained cleanly and characterized by 1H, 13C, 31P, and 29Si NMR analysis. Further reaction of 126 (M = Ge) with GeMe2 gave the 2,3-digerma-1-phosphacyclobutane 127 (Equation (38)) <2002MI1568>. XP=C(TMS)2 118

MMe2

TMS

X =Ph; M = Si, Ge

TMS

PPh MMe2 126

6.12.4.2.2

GeMe2; M = Ge

TMS TMS PPh Me2Ge GeMe2

ð38Þ

127

One phosphorus and three metal functions

The only reports since 1995 of compounds of this description involve organometallic complexes with carbons bearing, in addition to one phosphorus function, either three osmium functions or three cobalt functions. All of the reported syntheses of the former complexes involve CP bond formation upon displacement of chlorine from carbon bearing three osmium functions, and the sole reported synthesis of the latter involves CCo bond formation by displacement of chlorine from a carbon bearing one phosphorus function. The reaction of the triosmium alkylidene cluster [Os3(-H)3(CO)9(3-CCl)], 128, with various bidentate diphosphine ligands is outlined in Scheme 18. Cluster 128 reacted with an excess of butyldiphenylphosphine in the presence of a stoichiometric amount of DBU to give the expected complex 129 in 30% yield. A similar reaction was observed with the optically active diphosphine 130, affording a mixture of isomeric complexes 131 and 132 in 15% and 20% yields, respectively. Complex 131 decarbonylated at room temperature after 24 h to give an octacarbonyl homometallic

375

Functions Containing at Least One Group 15 Element

cluster 133 in 50% yield. The isomeric complex 132 failed to cyclize under similar conditions, perhaps due to potentially unfavorable steric interactions in the corresponding six-membered ring <1995JCS(D)2831> (Scheme 18). PPh2Bu

Os

Os

H Os BuPPh2, DBU

Ph2P

30%

Os

Os H

Me Ph3P Os

H Os

Ph Me H

Os

Os

H Os

PPh2 130

Ph P

H Me

129

Cl H

PPh2

H

PPh2

Os

H Os

H

H

, DBU 132

134

131, 15%; 132, 20%

H

H

Me

PPh2

Me Ph2P

Ph2P

128

Os

CH2Cl2, 24 h

Os

H Os

Os

50%

H

H Os

H Os

PPh2

H

133

131

Scheme 18

Complexes 135 (45% yield) and 136 (50% yield) were formed in a similar way from the reaction of 128 with the bidentate ligands Ph2PCH2PPh2 and Ph2PCH2CH2PPh2, respectively, (Scheme 19) <1996JOM(518)227>. Both subsequently decarbonylated and cyclized to form five- and six-membered osmacyclic complexes 137 (60% yield) and 138 (40% yield), respectively, whereas treatment of cluster 128 with the homologous ligand Ph2PCH2CH2CH2PPh2 led to an acyclic, linking complex 139. PPh2CH2PPh2 Ph2PCH2PPh2, DBU 45%

Ph2P

CH2Cl2, 2 days

Os

Os

H Os

Os 60%

H

Os

H Os 137

135

PPh2CH2CH2PPh2 Ph2PCH2CH2PPh2, DBU

Ph2P

CH2Cl2, 2 days

Os

128 50%

Os

H Os

Os 40%

H

Os

H Os

136

138

PPh2

PPh2

Ph2PCH2CH2CH2PPh2, DBU

Os 40%

PPh2

H

H Os

Os

Os

H

H Os 139

Scheme 19

Os H

H

PPh2

376

Functions Containing at Least One Group 15 Element

The ferrocenyl-phosphine cluster derivative 140 was prepared in a similar fashion by the reaction of cluster 128 with 1,10 -bis(diphenylphosphino)ferrocene (Equation (39)) <1995JCS(D)1379>. Ph2P

Ph2P 128

+

Fe

DBU, CH2Cl2, 30 min

Fe

32%

PPh2

Os H Ph2 P

Os

ð39Þ

Os H

140

The formation of a tricobalt carbonyl cluster (141; R = Et) was accomplished by treatment of [Co2(CO)8] with Cl3CP(O)(OEt)2 (Equation (40)) <1997JOM(541)417>. A similar complex (141; R = TMS) was also prepared either by treatment of [Co2(CO)8] with Cl3CP(O) (OTMS)2 or by reaction of 141 (R = Et) with TMSBr (in 15% yield for the latter). The Lewis donor ability of the P¼O function of cluster 141 (R = Et) was used to assemble early-late metal systems by reaction with [Cp2MCl]+ (M = Ti, Zr). O (RO)2P O (RO)2P Cl

Cl

THF, 50 °C, 3 h

+ Co2(CO)8

(OC)3Co

28%, R = Et; 23%, R = TMS

Cl

Co(CO)3

ð40Þ

Co (CO)3 141

6.12.4.2.3

One phosphorus, one silicon, and two metal functions

Two reports describing the preparation of compounds of this type have appeared since 1995; one describing a symmetrical complex with two carbons each bonded to one phosphorus atom, one silicon atom and two rhodium atoms, and a second outlining a structural investigation of a dilithiated phosphonate with a carbon bonded to one phosphorus atom, one silicon atom and two lithium atoms. Photolysis of rhodium-substituted triethylsilyldiazomethyl complex 142 led to the dimer 143, most likely via the intermediacy of a transient rhodium-stabilized carbene (Equation (41)) <1996OM1166>.

(Et3P)3Rh

N2 TMS

Benzene, 25 °C, 90 min, hν = 330 nm Unstable > –20 °C

TMS PEt3 PEt3 Et3P Rh Rh Et3P PEt3 Et3P TMS

ð41Þ

142 143

Treatment of a solution of dimethyl(trimethylsilylmethyl)phosphonate in TMEDA at 78 C with 2.5 equiv. of BunLi gave the crystalline dilithiated phosphonate 144, whose X-ray crystal structure revealed a highly aggregated species that is characterized by a LiOLiO fourmembered ring at its core (Equation (42)) <1999AG(E)92>. O (MeO)2P

TMS

i. 2.5 BunLi, TMEDA, –78 °C; ii. rt, 24 h

O (MeO)2P Li

+. . – TMS . N(Me)2 . (Li (TMEDA)2) (TMEDA) Li 2 3 2

144

ð42Þ

Functions Containing at Least One Group 15 Element

377

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1998POL2029

Functions Containing at Least One Group 15 Element

379

Biographical sketch

Shahrokh Saba was born in Tehran, Iran, studied at the American University of Beirut, in Lebanon where he obtained his B.S. in 1970. He continued his education at the University of East Anglia and received his Ph.D. in 1974 under the direction of Professor A. R. Katritzky. During 1975–1979 he taught as an Assistant Professor at Azad University in Tehran. He moved to the United Stated in 1980 and after postdoctoral fellowships in 1980 (Professor R. Breslow, Columbia University), 1981 (Professor W. C. Agosta, Rockefeller University), and 1982–1983 (Professor N. O. Smith, Fordham University) assumed a teaching position at Kean College, New Jersey in 1984. He returned to Fordham University in 1986 and took up his present position, and is currently an Associate Professor of chemistry. His scientific interests include all aspects of heterocyclic chemistry, and new uses of simple ammonium salts in organic synthesis.

James A. Ciaccio was born in Newburgh, NY, studied at SUNY, Oneonta where he obtained a B.S. in chemistry. His graduate studies in organic chemistry were conducted at SUNY, Stony Brook, where he obtained a Ph.D. under the direction of Professor T. W. Bell. In 1989 he was awarded a Camille and Henry Dreyfus Postdoctoral Teaching and Research Fellowship at Bucknell University, where he was Visiting Assistant Professor of Chemistry while working in the laboratories of Prof. H. W. Heine. During 1989–1990 he taught as Visiting Assistant Professor of Chemistry at Bard College, after which he took up his present position at Fordham University, where he is currently Associate Professor of Chemistry and Director of the General Science Program. His scientific interests fall in the general area of organic synthetic methods with emphasis on reactions and synthesis of epoxides and other heterocycles. He has also published several novel undergraduate organic laboratory experiments that combine synthesis and mechanistic discovery.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 355–379

6.13 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen, or Group 15 Element; Also Functions Containing Four Metals P. D. LICKISS Imperial College London, London, UK 6.13.1 METHANES CONTAINING AT LEAST ONE METALLOID (AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENT) 6.13.1.1 Methanes Bearing Four Metalloid Functions 6.13.1.1.1 Four similar metalloid functions 6.13.1.1.2 Three similar and one different metalloid functions 6.13.1.1.3 Two similar and two different metalloid functions 6.13.1.2 Methanes Bearing Three Metalloid Functions and a Metal Function 6.13.1.2.1 Three similar metalloid functions 6.13.1.2.2 Other mixed metalloid functions 6.13.1.3 Methanes Bearing Two Metalloid and Two Metal Functions 6.13.1.3.1 Two Si and two metal functions 6.13.1.3.2 Two Ge and two metal functions 6.13.1.3.3 Two B and two metal functions 6.13.1.3.4 Other combinations of two metalloids and two metal functions 6.13.1.4 Methanes Bearing One Metalloid and Three Metal Functions 6.13.1.4.1 One Si and three metal functions 6.13.1.4.2 One Ge and three metal functions 6.13.1.4.3 One B and three metal functions 6.13.2 METHANES BEARING FOUR METAL FUNCTIONS 6.13.2.1 Methanes Bearing Four Similar Metals 6.13.2.2 Methanes Bearing Three Similar and One Different Metal Functions 6.13.2.3 Methanes Bearing Two Similar and Two Different Metal Functions 6.13.2.4 Methanes Bearing Four Different Metal Functions 6.13.3 METHANES BEARING MORE THAN FOUR METALLOID OR METAL FUNCTIONS

381

382 382 382 387 388 389 389 401 402 402 402 402 403 403 403 403 403 403 403 403 404 404 404

382 6.13.1

Functions Containing at Least One Metalloid (Si, Ge, or B) METHANES CONTAINING AT LEAST ONE METALLOID (AND NO HALOGEN, CHALCOGEN, OR GROUP 15 ELEMENT)

The structure of this chapter is based closely on the corresponding one in COFGT (1995), where it was noted that for the 47 different elements (i.e., not the elements specifically excluded in the title of the section, the lanthanides, the actinides, and Fr, Ra, and Tc) that were to be considered as substituents at a quaternary carbon, there are 230 300 different possible combinations of the metal substituents (not including a further 178 365 optical isomers generated by having four different elements as substituents). The number of these possible combinations discussed later is still below 0.1% of those possible thus indicating that there is still tremendous scope for the synthesis of such organometallic compounds. For the case of methanes bearing four metal substituents, it has been necessary to make some judgment about whether the species may be of interest to organic chemists. For example, compounds where the carbon is part of a metal carbide have been excluded.

6.13.1.1

Methanes Bearing Four Metalloid Functions

There are hundreds of compounds known containing a carbon substituted by four silyl groups. The many methods to prepare them have not developed much beyond those described in COFGT (1995), but some new variations of reagents and experimental conditions mean that yields are often improved. The surprising lack of compounds with no tetragermyl substitution at carbon was noted in COFGT (1995). Although this is no longer the case, very few compounds of this type are known even now. This is still presumably due to a lack of synthetic effort as many of the methods available for tetrasilylmethane synthesis should be suitable for the preparation of tetragermylmethanes. A small number of methanes substituted by four boron functions have been prepared and there are an increasing range of compounds containing either a variety of metalloid functions or mixed metalloid and metal functions.

6.13.1.1.1

Four similar metalloid functions

(i) Four Si functions (a) Tetrasilylmethanes from in situ coupling reactions. Symmetrical compounds containing the Si4C function may be prepared by in situ coupling reactions involving CCl4 or CBr4 and a group 1 or 2 metal. These reactions are discussed in more detail in <1995COFGT(6)377>. A few new examples have been reported recently; for example, the use of 4,40 -di-t-butylbiphenyl as a catalyst in the reaction of CCl4 with lithium powder at low temperature gives an 80% yield of (Me3Si)4C <1996T1797>, which is much better than that without the catalyst. The in situ method has also been used in the preparation of the spirocyclic compound 1 in 25% yield (Equation (1)) <1999CL317>. These syntheses rely on the relatively slow coupling reactions to form disilanes using Li or Mg and should be applicable to a wider range of silanes as long as the substituents are not too bulky. SiMe2Cl + SiMe2Cl

CCl4

+

Mg

Me2 Si C Si Me2

Me2 Si Si Me2

ð1Þ

1

(b) Formation by reaction between a trisilyllithiomethane and a halosilane. The reactions between trisilyllithiomethanes (for their synthesis, see Section 6.13.1.2.1 below) and halosilanes have been used to prepare a wide range of tetrasilylmethanes in which there are at least two different silyl substituents on the carbon. Such compounds are not accessible via the in situ coupling reaction, which produces only symmetrical compounds. This method is thus more general and often gives good yields. The only potential difficulty with these reactions is that the Si3CLi-substituted precursor may require stringent low-temperature conditions for its preparation.

Functions Containing at Least One Metalloid (Si, Ge, or B)

383

The bulk of a trisilyllithiomethane derivative together with the low-temperature preparations means that it is possible to prepare reagents containing functional groups that would not normally be compatible in simpler compounds. For example, reagents containing both SiH and CLi groups are accessible and can be used to give a range of compounds containing SiH groups that can then be used as precursors to many other tetrasilylmethanes. The range of trisilylithium reagents available for these reactions, together with the products available, is given in Table 1. As would be expected from simple metathesis reactions, the yields for this method are usually good. The order in which the silyl substituents are attached to the central carbon may be important if the groups are particularly bulky, and it seems best if the most bulky silyl substituent is not the one to be attached last. It should also be noted that addition of more than 1 equiv. of a trisilylmethyllithium reagent to a polyhalosilane does not result in more than monosubstitution at silicon; presumably this is due to the steric crowding at the relatively small silicon center. The reaction of (HMe2Si)3CLi with SiCl4 gives several products (see Table 1), the main one being the cyclic species 2, in approximately 38% yield <1999OM1804>. The generation of compounds containing more complicated tetrasilylmethane centers by this general route is exemplified by the syntheses of the bicyclic compounds 5 and 6 shown in Scheme 1 <1998CL1145, 2000JOM(611)12>. In this case, the intermediate organometallic reagent, 4, derived from the trisilylmethane derivative 3, is probably the potassium derivative in THF solution. In a related reaction to those described above, the treatment of the Grignard-like species [Mg(OEt)2{C(SiMe3)3}I]2 with Me3SiCl gives (Me3Si)4C in 23% yield <2001JOM(631)76>.

Me2 Si (HMe2Si)2C C(SiMe2H)2 Si Me2 2 Me2 Si Me2Si

H

Me2Si

C

BuLi/ButOK

SiMe2

Me2Si Me2Si

Me2 Si

H 3

Si Me2

SiMe2

Me2Si

THF, – 40 °C

C

M C

C H

Me2Si 4

Si Me2

RMe2SiCl Me2 Si Me2Si

Me2 Si

SiMe3 C SiMe2

Me2Si C

Me2Si Me3Si

Me2Si

R = Me

Si Me2

i. BuLi/ButOK ii. Me 3SiCl

C

SiMe2

Me2Si Me2Si

C H

98%

6

SiMe2R

Si Me2

R = Me, 82% R = Ph, 90 % R = CH2CH2CH2Cl, 86 %

5

Scheme 1

(c) Formation via addition reactions of silenes. The dimerization of silenes, Si¼C containing compounds, occurs readily at room temperature and usually gives head–tail dimers. If there are two silyl substituents at the unsaturated carbon center, then the resulting dimers contain two tetrasilylmethane centers. The silenes (Ph2MeSi)(Me3Si)C¼SiMe2 <1996JOM(524)147> and (Me3Si)2C¼SiPh2 <1995CB1241> undergo Ph and Me group migrations to give a mixture of isomeric silenes that dimerize in the head-to-tail fashion to give the disilacyclobutanes 7–10 in varying yields depending on the nature of the silene starting material. The silene (Me3Si)2C¼SiMe2 dimerizes in a similar manner <2000JOM(598)292>.

Table 1 Lithiomethane

Tetrasilylmethanes from the reaction of miscellaneous trisilyllithiomethanes with halosilanes

Halosilane

Product

R2C(SiMe2Ph)Li R2C(SiPh2Me)Lia

PhMeHSiCl Me2SiHCl

R2C(SiMe2Ph)(SiPhMeH) R2C(SiPh2Me)(SiMe2H)

R2C(SiPh2Me)Li R3CLi R3CLi

Me3SiCl EtSiCl3 BunSiCl3

R3CSiPh2Me R3CSiEtCl2 R3CSi(Bun)Cl2

R3CLi R3CLi R3CLi R3CLi R3CLi R3CLi R3CLi R3CLi

(p-MeOC6H4)SiCl3 (p-MeOC6H4)MeSiF2 (p-MeOC6H4)2SiF2 Si2Cl6 Me3SiCl Me2SiHCl CH2¼CHMeSiCl2 (p-MeOC6H4)2SiMeHCl

R3CSi(p-MeOC6H4)Cl2 R3CSiMe(p-MeOC6H4)F R3CSi(p-MeOC6H4)2F R3CSi2Cl4CR3 R4C R3CSiMe2H R3CSiMeClCH¼CH2 R3CSi(p-MeOC6H4)MeH

R3CLi

(p-MeC6H4)2SiMeHCl

R3CSi(p-MeC6H4)MeH

R3CLi R2C(SiMe2H)Li

Ph2SiF2 Me3SiCl

R3CSiPh2F R3CSiMe2H

R2C(SiMe2H)Li R2C(SiMe2H)Li R2C(SiMe2OPh)Li R2C(SiMe2SPh)li R2C(SiMe2SMe)Li (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (HMe2Si)3CLi (PriMe2Si)3CLi

Me2SiHCl Me2PhSiCl Me2SiHCl Me2SiHCl Me2SiHCl Me3SiCl MeSiHCl2 HSiCl3 MeSiCl3 SiCl4 SiCl4 CH2¼CHMe2SiCl CH2¼CHMeSiCl2 CH2¼CHCH2MeSiCl2 [CH2¼CH(CH2)4]Me2SiCl Me2SiHCl

R2C(SiMe2H)2 R2C(SiMe2Ph)(SiMe2H) R2C(SiMe2OPh)(SiMe2H) R2C(SiMe2SPh)(SiMe2H) R2C(SiMe2SMe)(SiMe2H) (HMe2Si)3CR (HMe2Si)3CSiMeHCl (HMe2Si)3CSiHCl2 (HMe2Si)3CSiMeCl2 (HMe2Si)3CSiHCl2b (HMe2Si)3CSiMe2CH(SiMe2H)2b (HMe2Si)3CSiMe2CH¼CH2 (HMe2Si)3CSiMeClCH¼CH2 (HMe2Si)3CSiMeClCH2CH¼CH2 (HMe2Si)3CSiMe2[(CH2)4CH¼CH2] (PriMe2Si)3CSiMe2H

Yield (%)

References

40 40

<1998JOM(560)41> <1995BSF517> <2001EJI481> <2001EJI481> <1996JCS(P2)163> <2000JOM(598)222> <2000PS(158)97> <2000PS(158)97> <2000PS(158)97> <1997JOM(545–546)61> <2001IC3766> <2001EJI481> <2001EJI481> <2000JOM(598)222> <2000JOM(598)222> <1999PS(149)229> <2000JOM(598)222> <1999PS(149)229> <2000JOM(598)222> <2000OM374> <2001JOM(640)29> <2001JOM(640)29> <2001JOM(640)29> <2001JOM(640)29> <2001JOM(640)29> <2001JOM(640)29> <1999OM1804> <1999OM1804> <1999OM1804> <1999OM1804> <1999OM1804> <1999OM1804> <2001JOM(620)127> <2001JOM(620)127> <2001JOM(620)127> <2001JOM(620)127> <1995JOM(489)181>

48 60 70 62 72 82 82 40 45

a

R ¼ Me3Si.

b

Formed as a mixture, together with compound 2.

30 63 69 64 47 43 31 98 91 20 96 26 8 89 85 87 92 77

385

Functions Containing at Least One Metalloid (Si, Ge, or B) Me2 Si

Me3Si C

SiMe3 C

SiMe2

R2 C

R2

R2

Me2 Si

SiMe3 C

SiMe2

R1 C

R2

Me2 Si

SiMe3 C

SiMe2

R1 C

R2

R1

Me3Si 7

Me2 Si

R1 C

SiMe2

R1

R1 9

8

10

R1 = SiMe2Ph R2 = SiMePh2

Photolysis or thermolysis of diazomethane precursors gives rise to the silenes 11, which undergo intramolecular head-to-tail additions to give the cyclic species 12 in low yield as components of complicated product mixtures (Equation (2)) <1995JOM(499)99>. Reaction of PhSiCl3 with {Li[C(PMe2)(SiMe3)2]}2xTMEDA occurs to give the phospha-alkene 13, which on prolonged reaction times or on storage gives 14 via a complicated mechanism thought to involve loss of PMe2Cl, formation of a silene intermediate, and both Me and SiMe3 migrations (Equation (3)) <1995JOM(501)167>.

Me2Si PhMe2Si

Me2 Me 2 Si Si

SiMe2

(

Si Me2

)

PhMe2Si

SiMe2Ph

C SiMe2Ph

C

n

( SiMe )

11

2

ð2Þ

n

n = 1 or 2 12 Ph Me Si SiMe3 (Me3Si)2C Me2Si PMe2

Me3Si Ph Me3Si Si P C(SiMe3)2 Me2 P Cl Me2 13

ð3Þ

14

Addition of Me3SiN3 to the THF adduct of the silene (But2MeSi)(Me3Si)C¼SiMe2 leads not to a cycloaddition but the formation (But2MeSi)(Me3Si)2CSiMe2N3 in 15% yield together with diazo-containing products <1996CB471>. Addition of a lithium reagent to a silene can also occur, thus reaction of TsiLi(Tsi=(Me3Si)3C) with the silene (Me3Si)2C¼SiMe2, at 95 C followed by warming to room temperature and work-up in the air affords (Me3Si)2CHSiMe2Tsi <2000JOM(598)292>. (d) Thermolytic or photolytic methods. Interest in the thermolysis of low-molecular-weight silanes to give complicated cyclic compounds has waned in recent years but the thermolysis of (Cl3Si)2CCl2 in a fluidized bed of Si/Cu has been revisited and shown to afford (Cl3Si)4C and the cyclic compounds 15 and 16 <1994ZAAC(620)136>. Similarly, thermolysis of the trisilacyclohexane derivative 17 over Si/Cu gives compounds 18 and 19 (Equation (4)) <1994ZAAC(620)1253>. Cl2Si

SiCl2 Cl2 Si C C Si SiCl3 Cl3Si Cl2

Cl2 Si Cl3Si C C Cl3Si Si Cl2

16 n = 0, 1, or 2

15

Cl2Si

SiCl2 Si Cl2 17

330 °C Si/Cu

Cl2 Si SiCl3 C Si n SiCl3 Cl2

Cl2Si

SiCl2 C SiCl3 Si SiCl3 Cl2 18

Cl2 Si +

Cl2Si

Cl2 Si C C Si Si Cl2 Cl2 19

Cl2 Si SiCl2 Si Cl2

ð4Þ

386

Functions Containing at Least One Metalloid (Si, Ge, or B)

(e) Other methods. No recent examples of transition metal catalyzed syntheses or carbosilane rearrangements catalyzed by AlBr3 as methods for preparing tetrasilylmethanes seem to have been published. These methods are discussed in <1995COFGT(6)377>. The reaction between Me3GeSiCl3 and phosphaalkenes 20 led to an unusual P¼C bond cleavage and the formation of the cyclic species 21 (Equation (5)) <2002AG(E)3829>. Me3Si

P

Me3Si

PPriR1

Cl2 Si Me3Si C P PPriR1 Me3Si Si Cl2

Toluene 2 h, rt

20

ð5Þ

21

R1 = Pri or But

(ii) Four Ge functions The surprising absence of tetragermylmethane derivatives was noted in the reference <1995COFGT(6)377> and was attributed to a lack of synthetic effort in this area rather than to any inherent instability of such compounds. More recently, a need for the synthesis of tetragermylmethanes has been generated by the semiconductor and chemical vapor deposition community and this has led to the preparation of a small number of these compounds. The synthesis of (BrCl2Ge)4C and (Br3Ge)4C can be achieved in 80% and 95% yields, respectively, via the insertion of GeX2dioxane (where X = Cl or Br, respectively) into the CBr bonds of CBr4 <1998JA6738, 1995IC5103>. Reduction of these perhalo compounds with LiAlH4 gives (H3Ge)4C in 20% yield, which has been used as a precursor to various semiconductor materials via thermal decomposition .

(iii) Four B functions Compounds containing the CB4 grouping in which the CB bonds are simple two-center twoelectron bonds are rare, much more common are the polyhedral carboranes where multicenter bonding predominates. This chapter will not discuss carboranes, more information about them can be found in several reviews <2002CCR(232)173, 2002CCC869, 2000JOM(614)10, 1999CCC895>. One of the very few preparations of a tetraboramethane derivative is shown in Equation (6), in which a boriranylideneborane, 22, reacts with tetrahalodiboranes. If the substituents at boron are aryl rather than alkyl, then products containing the CB2Si2 grouping are formed (see Section 6.13.1.1.3) <2001EJI387>. But B

B

But

Hexane

+ B2X4 (Me3Si)2C

–85 °C

C 22

X But Me3Si B B X C C Me3Si B X B X But

ð6Þ

X = Cl, 92%; X = Br, 82%

Despite the lack of synthetic interest in simple compounds containing the CB4 grouping, there has been theoretical interest as the computational search for species containing planar four-coordinate carbon reveals that the ‘‘boraplane’’ 23 does have a D4h arrangement at the central carbon. An experimental confirmation of this planarity does not seem to have been carried out <2001JA994>.

B

B C

B

B

23

387

Functions Containing at Least One Metalloid (Si, Ge, or B) 6.13.1.1.2

Three similar and one different metalloid functions

(i) Three Si functions and one Ge function The ready availability of trisilyllithiomethane derivatives (see Section 6.13.1.2.(i).(a) below) would suggest that the easiest route to Si3GeC compounds is the reaction of a germyl halide with an Si3CLi derivative. The reaction of (Me3Si)3CLi with GeCl4 in THF gives the expected (Me3Si)3CGeCl3 <1997T12215>, and the reaction of 1 equiv. of (Me3Si)3CLi with GeBr4 in toluene solution affords (Me3Si)3CGeBr3 but use of a 2:1 ratio of reagents does not give rise to [(Me3Si)3C]2GeBr2 but rather to (Me3Si)3C(PhCH2)GeBr2 in 64% yield. This is thought to be due to a loss of Tsi from the initially formed [(Me3Si)3C]2GeBr2 followed by formation of PhCH2 from the solvent and radical recombination of PhCH2 and (Me3Si)3CGeBr2 <1999ZAAC(625)1807>. Reaction of (Me3Si)3CLi with GeCl2 dioxane in THF solution gives the germylene [(Me3Si)3C]ClGe:LiCl3THF in 41% yield, which undergoes ready reaction with alkenes or with phenyl acetylene to give Ge(IV) products 24 and 25 resulting from (2+1)-cycloadditions (Scheme 2). A novel bicyclic digermane, 26, is formed on reduction of 25a with Mg/MgBr2 (Scheme 2) <1996OM3103>. Reaction of (Me3Si)2(2-NC5H4Me2Si)CLi with GeCl2 dioxane gives the monomeric organogermanium(II) chloride 27 in 72% yield <2001OM1223>. As in the case of [(Me3Si)3C]ClGe:LiCl3THF, the usual dimerization expected for such species is prevented by the steric protection afforded by the three bulky silyl substituents, intramolecular coordination via the pyridyl nitrogen also prevents an increase in coordination number at the Ge atom. The first structurally characterized organometallic ate complex of Ge(II), 28, has been prepared in 40% yield from the reaction of (Me3Si)3CLi with Ge(SBun)2 <2002OM4005>.

Ph

Cl Cl Tsi Ge Ge Tsi

H

Ph

Tsi Ge:.LiCl.THF Cl

Tsi = (Me3Si)3C

R1 R2

H

24

Cl Cl Tsi Ge Ge Tsi

H R3

R1

R2

H

R3

Mg/MgBr2 Ethylene, 25a

Tsi Ge

Ge Tsi

26, 68%

25a, R1 = R2 = R3 = H b, R1 = R2 = H, R3 = Me c, R1 = R2 = H, R3 = Ph d, R1 = R2 = Me, R3 = H

Scheme 2

Me2Si Me3Si C Me3Si

BuS Me3Si SBu THF Me3Si C Ge Li S THF Me3Si S

N Ge Cl

27

28

(ii) Three Si functions and one B function Relatively few new syntheses of compounds containing the Si3BC grouping were reported in the 1990s; most of the recent chemistry of such compounds deriving from compounds prepared before COFGT (1995) was published. The most obvious route to Si3BC-containing compounds is to treat a boron trihalide with a trisilyllithium reagent. Thus, the reaction between (Me3Si)3CLi and BCl3 gives the expected monosubstituted product (Me3Si)3CBCl2. Substitutions at the BCl bonds may then be carried out to generate further compounds containing the Si3BC grouping <1997JOM(536)361>. A more complicated route has been found to be the addition of a silylene

388

Functions Containing at Least One Metalloid (Si, Ge, or B)

to an unsaturated species. Thus, addition of Me2Si: to MeB¼C(SiMe3)2 is thought to lead initially to a three-membered ring, which undergoes further reaction with a second equivalent of MeB¼C(SiMe3)2 to give ring expansion and the formation of 29 in 77% yield <1995OM1507>. Me2 Si C(SiMe3)2 (Me3Si)2C B B Me Me 29

(iii) Three Ge functions and one Si or B function; also three B functions and one Si or Ge function Considering the dearth of compounds containing the CGe4 function, it is, perhaps, not surprising that there are a few trigermylmethyl derivatives known. Only one compound, (Me3Ge)3CSiBut2F, containing the CGe3Si grouping seems to have been prepared. It can be made in 20% yield by reaction of (Me3Ge)2(FBut2Si)CLi2THF with Me3GeCl <1996JOM(511)239>. No doubt many other derivatives could be prepared in a similar way. No compounds with the CGe3B grouping seem to be known. Again, this lack of compounds is not likely to be due to a problem of inherent instability of such species but rather a lack of interest in their synthesis. Apart from the silyl- and germyl-substituted carboranes, there is a lack of CB3Si or CB3Ge functions, which is surprising when one considers that several compounds containing the CB4 function are known (see Section 6.13.1.1.1). However, the first triboracyclobutane 30 can be prepared according to Equation (7) from the triboracyclobutanide 31 in 50% yield <2003AG(E)669, 2003AG(E)671>. The synthesis of these mixed metalloid compounds could probably be easily achieved in a manner similar to those already known, i.e., via metathetical reactions between a metalloid-substituted methyllithium derivative and an element halide. SiMe3 Me3Si

Dur

C B B B Dur 31

6.13.1.1.3

CH2SiMe3 +

Li

Cl2BCH2SiMe3

–LiCl

C Dur

B

Me3SiCH2 B Cl Dur = duryl, 2,3,5,6-Me4C6H

B

Dur

B

ð7Þ

CH2SiMe3 30

Two similar and two different metalloid functions

(i) Two Si and two Ge functions When one considers that there are a large number of compounds containing the CSi4 function and a few CGe4 function known, it might be expected that there will only be a handful of compounds known that contain the CSi2Ge2 function. This is indeed the case. Such compounds have been prepared using methods that have been widely used for the synthesis of CSi4 functions and many more species could no doubt be prepared in similar ways. Little work has been done with these compounds since that reported in <1995COFGT(6)377>, but more examples of the elimination of LiX from XMe2GeCLi(SiMe3)2 compounds (where X = F, Br, OMe, or OPh) to give Me2Ge¼C(SiMe3)2, which dimerizes to give the head-to-tail dimer [Me2GeC(SiMe3)2]2, have been reported <2000JOM(598)292, 2000JOM(598)304>.

(ii) Two Si, one Ge, and one B functions Compounds containing the CSi2GeB function do not appear to be known. They are likely, however, to be readily available from the reaction of one of the several known CSi2GeLi containing compounds with a boron halide or B(OMe)3.

389

Functions Containing at Least One Metalloid (Si, Ge, or B) (iii) Two Si and two B functions

There are very few compounds known containing the CSi2B2 grouping but two such compounds have been prepared using addition reactions to unsaturated boranes. Thus reaction of methylideneborane 32 with the three-membered species 33 gives the five-membered species 34 in 81% yield (Equation (8)) <1995OM1507> and the borataalkyne 35 reacts with Me2SiHCl to give the bicyclo[1.1.1]pentane derivative 36 in 73% yield (Equation (9)) <1995AG(E)657>. But N Me B C(SiMe3)2

Bu

But N

t

B

+ But

32

B

B

But

Me

B

B

But

C SiMe 3 SiMe3

33

ð8Þ

34 Me mes – – B C B mes Me3Si 2 Li+ SiMe3

–2 LiCl + 2Me2SiHCl

–Me2SiH2

Me3Si

C

Me Si B B

C SiMe3 mes

ð9Þ

mes

35

36

The boriranylideneboranes 37 react with B2Cl4 to give the unsaturated species 38 (Equation (10)). If the substituent on boron is But rather than the aromatic group, then B4C-containing species are produced, see Section 6.13.1.1.1 <2001EJI387>. Ar

Ar

Ar B

B

Hexane +

(Me3Si)2C

C

B2Cl4

–85 °C

Cl

Me3Si Me3Si C B Cl2B

Cl Ar

ð10Þ

37 38, Ar = C6Me4H, 50% Ar = C6Me3H2, 33%

(iv) Two Ge and two B functions; two Ge, one Si, and one B functions; and two B, one Si, and one Ge functions As might be expected from the paucity of CSi2Ge2 and CSi2B2 containing species, there appear to have been no compounds prepared containing the CGe2B2, CGe2SiB, or CB2SiGe functions. Again, there is unlikely to be any good reason why such compounds should not be made. Reactions between appropriately substituted lithiomethanes and halometalloids should readily afford the required functions.

6.13.1.2 6.13.1.2.1

Methanes Bearing Three Metalloid Functions and a Metal Function Three similar metalloid functions

(i) Three Si functions (a) Three Si and one group 1 metal functions. There has been a surge of interest in the preparation and use of trisilyllithiomethane derivatives because of the previous widespread application of (Me3Si)3CLi and (PhMe2Si)3CLi as bulky alkyl group transfer reagents popularized by Eaborn and Smith <2001JCS(D)1541, 2001JCS(D)3397>. The chemistry and structures of compounds containing these bulky groups have been reviewed. Table 2 gives details of how many of the trisilyllithium lithium reagents available may be prepared. Several general points can be made. There are two main

Table 2 Trisilyllithiomethanes from the reactions of trisilylmethane derivatives and various metallating agents Trisilylmethane derivative R3CH R3CH R3CCl (HMe2Si)3CH (PriMe2Si)3CH (Ph2PCH2Me2Si)3CH (Ph2PMe2Si)3CH (Me2NMe2Si)3CH (o-MeC6H4Me2Si)3CH [(EtO)3Si]3CH R2(CyMe2Si)CH R2(PhMe2Si)CH R2(PhMe2Si)CH R2(PhMe2Si)CH R2(PhMe2Si)CH R2(Ph2MeSi)CH R2(2-C5H4NMe2Si)CH R2(MeOMe2Si)CCl R(MeOMe2Si)2CH R(MeOMe2Si)2CH R2(BrMe2Si)CBr R(FMe2Si)(But3Si)CBr R(TfOMe2Si)(But3Si)CBr R2(Ph2PMe2Si)CH R2(Ph2PCH2Me2Si)CH R2(Me2NMe2Si)CCl R2(Me2NMe2Si)CH R(Me2NMe2Si)2CH [(Me3Si)2CHSiMe2]2O [HCR2SiMe2CH2]2 [HCR2SiMe2CH2]2 a R = Me3Si. examples.

b

a

Metallating agent and conditions

Trisilyllithiomethane product

MeLi, THF/Et2O BunLi, hexane Li, toluene, 85–90 C LDA, THF MeLi, THF, 48 h reflux MeLi BuLi, hexane, TMEDA MeLi, THF BuLi, petroleum, TMEDA ButLi, THF, –65 C MeLi, THF MeLi, Et2O MeLi, THF/TMEDA MeLi, THF MeLi, petroleum/TMEDA MeLi, THF/Et2O, 4 h reflux, MeLi, THF BuLi, THF, 78 C MeLi LDA PhLi, low temp. 2 PhLi 2 BunLi MeLi MeLi BuLi, THF, –78 C MeLi, THF BuLi MeLi, THF MeLi, THF/TMEDA MeLi, THF

R3CLi R3CLi, base-free R3CLi, base-free (HMe2Si)3CLi (PriMe2Si)3CLi 41 [Li(TMEDA)2][(Ph2PMe2Si)3C] [(Me2NMe2Si)2CLi]1 [Li(TMEDA)2][(o-MeC6H4Me2Si)3CLi] [(EtO)3Si]3CLi R2(CyMe2Si)CLiTHF R2(PhMe2Si)CLiEt2O R2(PhMe2Si)CLiTMEDA R2(PhMe2Si)CLi2THF R2(PhMe2Si)CLiTMEDA R2(Ph2MeSi)CH 39 R2(MeOMe2Si)CLi2THF mixtureb R(MeOMe2Si)2CLi R2(BrMe2Si)CLic R(PhMe2Si)(But3Si)CLi R(BuMe2Si)(But3Si)CLi R2(Ph2PMe2Si)CLi2THF 42 40 40 R(Me2NMe2Si)2CLi 43 [Li(TMEDA)2]+ salt of 44 [Li(THF)4]+ salt of 44

Reaction occurs at both the methine CH and at SiOMe bonds.

c

Yield (%)

86 66 65 84 92 54 54

67 90

75 ca. 90 87 59 53 90 79 43

References <1999MI813> <1997JOM(536–537)361> <1997ZAAC(623)1455> <1999OM1804> <1995JOM(489)181> <2000JCS(D)2183> <1999JCS(D)831> <1996CC741> <1997OM6035> <1998JOM(562)79> <2001MI(162)225> <1997OM4728> <1997OM4728> <1997OM4728> <1997OM4728> <1995BSf517> <2000OM3224> <1998OM4322> <1999JCS(D)3267> <1999JCS(D)3267> <2000CJC1412> <1997JOM(531)47> <1997JOM(531)47> <2000JCS(D)2183> <2000JCS(D)2183> <1999OM45> <1999OM45> <1999JCS(D)3267> <1998CC1277> <1996OM1651> <1996OM1651>

This lithium species eliminates LiBr at room temperature to give the silene (Me3Si)2C¼SiMe2, see text for other related

391

Functions Containing at Least One Metalloid (Si, Ge, or B)

synthetic routes, metallation of an Si3CH substituted carbon, usually by MeLi or BuLi, and treatment of an Si3CX (X = Cl or Br) substituted carbon with lithium metal. The first method is more common as it is often easier to make the Si3CH grouping compared to the corresponding Si3CX and complications arising from the incorporation of LiX into reactions following the preparation of the trisilylmethyllithium reagent are avoided. The yields given in Table 2 are for lithium reagents isolated as solids and fully characterized. The yield of those species without an entry in the yield column can be determined indirectly from the yields of derivatives from subsequent reactions. There has been interest in recent years in the preparation of ‘‘base-free’’ trisilylmethyllithium reagents, i.e., not containing coordinated solvent such as THF or Et2O that can either react or be incorporated into products in further reactions. Such syntheses are carried out in alkane or aromatic solvents and the reagent formed usually contains no solvent, the lithium atoms being coordinated by alkyl or aryl groups within the trisilylmethyl substituent. Another extension to this area has been the preparation of reagents containing one or more potentially reactive or coordinating groups within the trisilylmethyl group. Thus, groups such as (RMe2Si)(Me3Si)2C, where R = OMe, NMe2, 2-pyridyl, or PPh2, can be transferred via their lithium derivatives to a range of transition metal centers where intramolecular coordination by the group R promotes monomer formation and discourages formation of oligomeric species. This synthetically useful range of reagents will no doubt be expanded in the future to include other more complicated ligating groups. A recent example, (Me3Si)2(HMe2Si)CLi(THF)2, containing a reactive SiH group can be prepared by treating (Me3Si)2(HMe2Si)CH with MeLi <2004JOM(689)1238>. The various methods for the preparation of TsiLi, the most popular of the trisilyllithium reagents, have been described in <1995COFGT(6)377>, but some new variations are included in Table 2. Sublimation of TsiLi2THF gives a small amount of TsiLi1.5THF while reaction of base-free TsiLi with O2 in toluene gives (Me3Si)2C¼O, which forms a 1:1 adduct with TsiLi to give TsiLiO¼C(SiMe3)2 <2000ZAAC(626)2040>. Solid-state 7Li NMR studies of base-free TsiLi and some of its adducts have also been carried out in order to investigate further the range of structures adopted by this useful reagent <2000JA9858>. The presence of coordinating groups in the trisilylmethyl substituent leads to species in which intramolecular coordination occurs to give monomeric species such as 39–41 (see Table 2 for details of the syntheses) in which some or all of the coordinating solvent is excluded. Despite the wide variety of structures that have found to be adopted by these species in the solid state, they all act as simple trisilylmethyl derivative transfer agents in solution. The use of these reagents in the synthesis of trisilylmetallamethane derivatives is detailed extensively in following sections. If two readily metallated carbons are present in a molecule, then a double metallation can occur as shown by compounds 42–44. Compound 43 is a molecular species containing an unusual interaction between the relatively low-basicity siloxane oxygen and a lithium, and the [Li(TMEDA)2]+ salt of anion 44 can be used to make a range of divalent organometallic complexes as detailed in the following sections.

N Me2Si Me3Si C Li THF Me3Si 39 Me2 Li(THF)2 Si Me3Si C PPh2 Me3Si Li THF

Me2Si

40

Me2Si (THF)2Li O Me2Si

Ph2 P Ph2 Li P C

Ph2 P

Me2Si NMe2 Me3Si C Li(THF)2 Me3Si

41

SiMe3 C SiMe3 Li C SiMe 3

Me2Si (Me3Si)2C

SiMe2

SiMe2 SiMe2 C(SiMe3)2

Li

SiMe3 42

43

44

Although few examples of polycyclic trisilyllithiomethanes have been reported recently (compared to the many described in <1995COFGT(6)377>), the bicyclic species 3 can be monometallated, then derivatized and then metallated at the second methine center and further derivatized as shown in Scheme 1 above. A further series of trisilyllithiomethanes that have received detailed study are of the general form (XR2Si)CLi(SiMe3)2 where R is an alkyl or aryl group and X is an electronegative function such as halide or alkoxide. As might be expected, these compounds need to be prepared at low temperature as they readily eliminate LiX (at different temperatures depending on the nature of X) to give silenes R2Si¼C(SiMe3)2. For example,

392

Functions Containing at Least One Metalloid (Si, Ge, or B)

reaction between (XPh2Si)(Me3Si)2CBr (X = F or Br) with BuLi or PhLi at 78 C in Et2O gives (XPh2Si)(Me3Si)2CLi, which then generate Ph2Si¼C(SiMe3)2 <1995CB1231, 1995CB1241> and (XMe2Si)(Me3Si)2CBr (X = alkoxide or halide) react with BuLi or PhLi at low temperature to give (XMe2Si)(Me3Si)2Cli, which can then be used to generate Me2Si¼C(SiMe3)2 <2000CJC1412, 2000JOM(598)292, 2000JOM(598)304>. Trisilyllithiomethane derivatives sometimes result unexpectedly from complicated reactions and rearrangements, the relative stability of trisilylmethyl anions perhaps being a driving force for this. For example, (Me3Si)2(HMe2Si)CLi is found to be an intermediate in the reaction between MeLi and Me3SiSiMe3 <2000OM374>, and the disilylmethane derivative (MeOMe2Si)2CH2 reacts with ButLi in pentane at 78 C to give (MeOMe2Si)2CHLi, which undergoes a remarkable skeletal rearrangement to give the previously prepared dimer 45 (intra- and intermolecular coordination of Li in [{LiC(SiMe2OMe)3}2]; methyl groups have been omitted for clarity) in 64% yield <2003OM2505>. O

Si

O

Si

Li

O Si

C Si Si

O O

C Li

Si O

45

The popular synthetic use of trisilylmethyllithium derivatives, particularly in transition metal chemistry, has prompted the synthesis of similar species incorporating heavier group 1 metals. Clearly, such compounds are likely to be more difficult to prepare being intolerant of ether solvents, and will be more difficult to handle because of their sensitivity toward water and oxygen. Despite these problems there are now well-characterized sodium, potassium, rubidium, and caesium derivatives of trisilylmethanes, some of which have been shown to be synthetically useful. Sodium derivatives can be prepared in a similar way to some of their lithium analogs, for example, (PhMe2Si)(Me3Si)2CH reacts with MeNa in petroleum containing TMEDA to give (PhMe2Si)(Me3Si)2CNaTMEDA in 34% yield <1997OM4728>. Alkali metal exchange may also be a useful synthetic route in preparing sodium compounds; thus, reaction of (Ph2PMe2Si)(Me3Si)2CLi2THF reacts with ButONa to give (Ph2PMe2Si)(Me3Si)2CNa in which the sodium is coordinated to both the carbanionic center and to a phenyl group <2000JCS(D)2183>. In the search for stable silenes, even more bulky trisilylmethane derivatives have been prepared, e.g., treatment of (FMe2Si)(But3Si)(Me3Si)CBr with But3SiNa affords (FMe2Si)(But3Si)(Me3Si)CNa, which can then potentially eliminate NaF <1997JOM(531)47>. Trisilylmethylpotassium derivatives can be prepared in a similar manner to the analogous lithium compounds. Thus, reaction of TsiH with MeK in Et2O in the presence of TMEDA gives TsiKTMEDA in 34% yield, (Me3Si)2(PhMe2Si)CH reacts with MeK in Et2O at 20 C to give (Me3Si)2(PhMe2Si)CK in 60% yield <1997OM4728>, and (MeOMe2Si)2(Me3Si)CH reacts with MeK to give (MeOMe2Si)2(Me3Si)CK cleanly <1999JCS(D)3267>. If (Me3Si)2(PhMe2Si)CK is crystallized from benzene, orange crystals of the potassate [K(C6H6)][K{C(SiMe3)2(SiPhMe2)}2] may be isolated <1995AG(E)2679>. The reactivity of the potassium compounds can be shown from the reaction of the vinyl derivative, (Me3Si)2(CH2¼CHMe2Si)CK (prepared from (Me3Si)2(CH2¼CHMe2Si)CH and MeK) with adventitious silicone grease in its container over a period of 4 weeks to give [K(SiMe2O)7][K{C(SiMe3)2(SiMe2CH2¼CH)}2] <1995AG(E)2679>. Alkali-metal exchange may also be useful as a synthetic route, species 39 reacts with ButOK to give the potassium analog (2-C5H4NMe2Si)(Me3Si)2CK which contains no solvent, the potassium being coordinated as shown in 46 in a polymeric structure <2000OM3224>.

Me2Si C

N Me2Si

N

K

K

C

Me3Si SiMe3 Me3Si SiMe3 46

Functions Containing at Least One Metalloid (Si, Ge, or B)

393

The [Li(THF)4]+ salt of 44 can also be used in the preparation of the dipotassium species 47, or a benzene solvate of the same species, 48 can be prepared directly from 49 as shown in Scheme 3 <1999OM2342>. The dicaesium compound 50 can be prepared in a similar manner <2000OM1190>.

[Li(THF)4] 44

MeLi, THF

ButOK, THF

CH2Me2Si(Me3Si)2CK(THF)2 CH2Me2Si(Me3Si)2CK(THF)2

CH2Me2Si(Me3Si)2CH CH2Me2Si(Me3Si)2CH 49 MeK, C6H6

i. MeCs, Et2O ii. Cryst. from C6H6

CH2Me2Si(Me3Si)2CK(C6H6) CH2Me2Si(Me3Si)2CK(C6H6)

47

CH2Me2Si(Me3Si)2CCs(C6H6) CH2Me2Si(Me3Si)2CCs(C6H6) 50

48

Scheme 3

Rare examples of structurally characterized alkylrubidium and caesium derivatives can be made using the reaction between MeM (M = Rb or Cs), prepared in situ from MeLi and the corresponding alkali-metal-2-ethylhexoxide, and TsiH. Thus, TsiRb is prepared in 64% yield and comprises an infinite chain of alternating planar Tsi anions and Rb+ cations, and TsiCs crystallizes from benzene to give TsiCs3.5C6H6 in which the Cs is coordinated to both the carbanion center and three benzene molecules <1995AG(E)687>. Similar reactions but using (PhMe2Si)3CH as starting material give (PhMe2Si)3CRb and (PhMe2Si)3CCs in yields of 74 and 66%, respectively <1997OM4728>. The structure of the rubidium species shows that the rubidium is coordinated by the aromatic groups of the trisilylmethyl substituent. The uses of these Na, K, Rb, and Cs derivatives of trisilylmethanes are largely unexplored but the widespread use of the Li analogs suggests that they may well have significant potential, particularly in organometallic chemistry. (b) Three Si and one group 2 metal functions. The reaction of (Me2NMe2Si)3CI with Mg in Et2O gives (Me2NMe2Si)3CMgI in 54% yield. Although it has the general Grignard reagent formula of RMgX, a structural study has shown that the central carbanionic carbon has a planar environment and that there is in fact no significant CMg interaction, the coordination sphere of the Mg comprising three nitrogen and one iodide ligand <1997OM503>. The reaction of (MeOMe2Si)(Me3Si)2CI with Mg in Et2O is thought to give the Grignard reagent (MeOMe2Si)(Me3Si)2CMgI, which decomposes to give the dialkylmagnesium species Mg{C(SiMe3)2(SiMe2OMe)}2 in 50% yield together with MgI2(OEt2)2. The Grignard compound can however be isolated in 80% yield from the reaction between (MeOMe2Si)(Me3Si)2CI and Mg in toluene solution <1996JOM(521)113>. A variety of other more complicated organomagnesium complexes containing solvent are also available from similar preparative routes. Thus, reaction of reagent 39 (see Section 6.13.1.2.1 above) with MgBr2 gives 51 <2000OM3224> but with [MgBr2(OEt2)2] the Li is retained to give complex 52 <2001JOM(631)76>. The ate complex, [Li(TMEDA)2][Li{C(SiMe3)2(SiMe2Ph)}2], reacts with MgBr2 in THF solution to give 53 in poor yield <2001JOM(631)76>. Grignard reagents 54 are formed when R3CI species (R = Me3Si or PhMe2Si) react with activated magnesium and an unusual, unsymmetrical dialkylmagnesium compound, 55, is obtained in 95% yield from the reaction between [MgBr2(OEt2)2] and the lithium reagent formed from BuLi and (Me2NMe2Si)(Me3Si)2CI in Et2O with <2001JOM(631)76>.

N Me2Si Me3Si C Mg THF Me3Si Br 51

Me2 THF Br N N Me2Si Mg Li (PhMe2Si)(Me3Si)2C Me3Si C Mg Br Br N Me3Si Me2 Br Li(THF)3 53 52 NMe2

Me2Si

R3C I OEt2 Mg Mg Et2O CR3 I

Me3Si C Mg OEt 2 Me3Si Bu

54, R = Me3Si or PhMe2Si

55

394

Functions Containing at Least One Metalloid (Si, Ge, or B)

The steric protection afforded by the Tsi group is seen clearly in the isolation of Tsi2Ca, the first solvent-free dialkylcalcium compound to be structurally characterized and which is obtained from the reaction between 2 equiv. of TsiK and 1 equiv. of CaI2 in 87% yield <1997CC1961>. Use of a bulky trisilyllithium reagent containing a group capable of intramolecular coordination allows the preparation of simple, monomeric dialkyl derivatives of strontium and barium. Thus, reaction of 2 equiv. of (MeOMe2Si)(Me3Si)2CK with MI2 (M = Sr or Ba) in THF affords [(MeOMe2Si)(Me3Si)2C]2M(THF)n, which when crystallized from methylcyclohexane, for M = Sr, gives [(MeOMe2Si)(Me3Si)2C]2Sr(THF) in 72% yield, and when crystallized from (Me2SiO)3/DME, for M = Ba, gives [(MeOMe2Si)(Me3Si)2C]2Ba(DME) in 68% yield <2003JA7534>. (c) Three Si and one group 12 metal functions. Reaction between TsiLi and ZnCl2 affords TsiZnCl in 26% yield as an isolated product after sublimation of the initially formed [Li(THF)4] [(TsiZn)2Cl3] <1998EJI1175, 1999JOM(572)249>. This is presumably also an intermediate in the sequential treatment of ZnCl2 with TsiLi followed by LiP(SiMe3)2 to give TsiZnP(SiMe3)2 in 60% yield <1995ZAAC(621)287>. Reaction of the trisilyllithiomethane derivative 39 containing a potentially chelating group with ZnBr2 or CdCl2 gives the halide-bridged dimers 56 and 57 in 67% and 69% yields respectively <2002JCS(D)2467> and reaction of reagent 40 with ZnBr2 affords an analogous cyclic dimer <2004JOM(689)1718>. The monomeric species 58 M = Zn is formed in 60% yield from the reaction of the [Li(TMEDA)2] salt of the diorganolithiate ion 44 with ZnCl2 <1999OM2342>. A series of crowded diorganomercury compounds have been prepared by metathesis reactions. Thus, TsiHgR compounds can be prepared by reaction of TsiHgBr with RMgX (R = Me, Pri, Bun, But, or Ph) and (PhMe2Si)3CHgR compounds from (PhMe2Si)3CHgCl and RLi (R = Me, Pri, Bun, But, or Ph). Treatment of (PhMe2Si)3CHgCl with TsiLi gives the extremely bulky (PhMe2Si)3CHgTsi in 21% yield. The symmetrical dialkylmercury derivative [(Me3Si)2(HMe2Si)C]2Hg is obtained in 16% yield from the reaction between HgCl2 and (Me3Si)2(HMe2Si)CLi at 110 C <1996JOM(510)143>. Other congested organomercury compounds containing potentially chelating groups can also be prepared by simple metathesis reactions. Thus, reaction between (MeOMe2Si)2Me3SiCK and HgBr2 gives (MeOMe2Si)2Me3SiCHgBr in 31% yield <1999JCS(D)3267>, reaction of 40 with HgBr2 gives [(Me2NMe2Si)(Me3Si)2C]2Hg in 51% yield <1999OM45>, reaction of 39 with HgCl2 gives 59 in 62% yield <2002JCS(D)2467>, and reaction of the [Li(TMEDA)2] salt of the diorganolithiate ion 44 with HgBr2 gives a 91% yield of 60 <1996OM1651>.

N Me2Si Me3Si C M X SiMe3 Me3Si X M C SiMe3 N SiMe2

SiMe2 C(SiMe3)2

Me2Si (Me3Si)2C M

58, M = Zn 60, M = Hg

N Me2Si Me3Si C Hg Cl Me3Si 59

56, M = Zn, X = Br 57, M = Cd, X = Cl

(d) Three Si and one group 13 metal functions. There has been increasing interest in compounds containing a Si3MC grouping (where M = Al, Ga, In, or Tl) and several such compounds have been found to be useful precursors to a wide range of novel organometallic compounds. The synthesis of these compounds relies largely on metathesis reactions between a bulky trisilyllithium reagent [for their synthesis see Section 6.13.1.2.1.(i).(a)] and a metal halide. One potential problem with this synthetic method is that coordinating solvents, such as THF or Et2O that are convenient to use in the synthesis of the organolithium reagent, may be cleaved by strong Lewis acidic group 13 compounds. For example, the reaction of TsiLi with BX3 (X = F, Cl, or Br) in Et2O affords TsiOEt and not TsiBX2 species <1995OM3098>. This problem can be avoided by the use of base-free trisilyllithium reagents [for their synthesis see Section 6.13.1.2.1.(i).(a)]. The reactions between bulky trisilyllithium reagents and aluminum halides give the products expected from metathesis reactions. For example, TsiAlMe2THF is formed in 85% yield from the reaction between TsiLi2THF and Me2AlCl in THF <1997CEJ1783> and the solventfree TsiAlMe2 is formed in 68% yield when base-free TsiLi in toluene is used <1997ZAAC(623)1455>. Similarly, reaction of (CyMe2Si)(Me3Si)2CLiTHF (Cy = cyclohexyl) with Me2AlCl gives (CyMe2Si)(Me3Si)2CAlMe2THF in 88% yield and which has been used to

Functions Containing at Least One Metalloid (Si, Ge, or B)

395

prepare a range of other (CyMe2Si)(Me3Si)2CAlX2 derivatives <2001MI(162)225>. The dimethyl derivative TsiAlMe2THF is also a useful precursor to other crowded alanes. For example, the reaction with Me3SnX (X = F or Cl) gives TsiAlX2THF, and with Br2 or I2 gives TsiAlBr2THF and TsiAlI2THF, respectively <1998OM2249>. Reduction of TsiAlI2THF by NaK alloy gives the tetrahedrane [TsiAl]4, analogous to the tetrahedranes of Ga, In, and Tl described below <1998AG(E)1952>. Base-free TsiLi reacts with AlCl3 at 78 C in a 1:1 ratio to give Li[TsiAlCl3] in 83% yield <1997ZAAC(623)1455> but if 2 equiv. of TsiLi are used then a methylation occurs to give TsiAlMeCl <2001ZAAC(627)715>. If a coordinating group is present in the trisilyllithium reagent or the aluminum halide, then solvent may be excluded from the coordination sphere of the aluminum in the product. For example, reaction of 40 with AlCl3 generates 61 in 91% yield <1999OM45>, reaction of (Me2NMe2Si)3CLi with AlCl3 in toluene containing THF gives 62 as a colorless solid in almost quantitative yield <1998OM3135>, and the product, 63, in Equation (11) is formed in 50% yield in THF solution <1995CB493>. However, the weaker basic OMe site in 64, derived from the reaction of (Me3Si)2(MeOMe2Si)CLi2THF with AlCl3 in 62% yield, does not prevent THF from coordinating to the Al <1998OM4322>. Me2Si NMe2 Me3Si C Al Cl Me3Si Cl

Me2 Me2NMe2Si Si NMe2 C Me2NMe2Si Al Cl2

61

(Me3Si)3CLi

62

+

NMe2

Cl Me3Si Me3Si C Al Cl MeOMe2Si THF 64

THF, –78 °C

NMe2 Al

Al Cl2

Cl

C(SiMe3)3

ð11Þ

63

Bulky trisilyllithium reagents have also been used to prepare sterically hindered aluminum hydrides, which are often monomeric in contrast to species containing less sterically demanding substituents. For example, the treatment of TsiLi with H3AlNMe3 readily affords TsiAlH2THF in 86% yield <2001OM2047>. Several trisilyllithium reagents, (RMe2Si)(Me3Si)2CLi (where R = Me, Ph, or NMe2), react with LiAlH4 in THF to give cyclic dimers 65 <1994OM4143, 2000JOM(597)3>. These structures all incorporate THF, excluding, in the case where R = NMe2, coordination of aluminum by the nitrogen. Treatment of the dimers where R = Me or Ph with Me3SiCl gives the simple hydrides (RMe2Si)(Me3Si)2CAlH2THF in 40% and 50% yields, respectively <2000JOM(597)3>. Reaction of 65, where R = Me, with 4 equiv. of 2,6-Pri2C6H3OH gives the diaryloxo species 66 in 75% yield and with Ph3SiOH the monomeric 67 is formed in 98% yield <2002JCS(D)3971>. The trisilyllithium reagent (MeOMe2Si)(Me3Si)2CLi2THF reacts with LiAlH4 in THF to give 68 in which the weakly basic SiOMe group does coordinate to the Li to exclude coordination by a second THF molecule <1998OM4322>. (The structure of 68 was later found to be dimeric <2000JOM(597)3>.) The reaction of (MeOMe2Si)2(Me3Si)CLi with LiAlH4 gives [Li(THF)4][(MeOMe2Si)2(Me3Si)CAlH3] <1999JCS(D)3267>.

H (RMe2Si)(Me3Si)2C Al H H

(THF)2 Li H H Al H C(SiMe3)2(SiMe2R) Li (THF)2 R = Me, 64% 65 R = Ph, 56% R = NMe2, 95%

OSiPh3 (Me3Si)3C Al OSiPh3 THF 67

R

R THF Li O O Al H Tsi R R R = Pri 66 Me3Si Me3Si

C

Al H2 Me2Si 68

H O Li Me THF

396

Functions Containing at Least One Metalloid (Si, Ge, or B)

Some remarkable polymetallic compounds have been isolated from the reaction between TsiLi and the gallium(I) halide GaBr. Thus, the reaction in toluene/THF at 78 C affords the lithium salt of the anion [Ga19Tsi6] in 30% yield <2000JA9178> and a small amount of the fused tetrahedrane derivative 69 <2001AG(E)1241>. The [Ga19Tsi6] anion contains a central Ga13 metal core surrounded by six Tsi–Ga substituents. Use of the simpler, related tetrahedrane [TsiGa]4, as a source of the monomer TsiGa for the preparation of a wide variety of organometallic compounds containing TsiGa as a ligand has been demonstrated (see, e.g., <2001IC750, 2000JCS(D)3133>). C(SiMe3)3 C(SiMe3)3 Ga Ga Ga Ga Ga C(SiMe3)3 (Me3Si)3C Ga Ga Ga C(SiMe3)3 C(SiMe3)3

(Me3Si)3C

Br

Li(THF)3

In (Me3Si)3C In Br In C(SiMe3)3 Br

69

71

The reaction of base-free TsiLi and GaX3 (X = Cl or I) at 78 C in a 1:1 ratio gives Li[TsiGaX3], but if 2 equiv. of TsiLi are used then a methylation occurs to give TsiGaMeCl <2001ZAAC(627)715>. Reaction of GaCl3 with (EtMe2Si)3CLi gives [Li(THF)4][(EtMe2Si)3CGaCl3] in 49% yield. Both this species and the (Me3Si)3C analog can be reduced by magnesium to give the corresponding tetragallium tetrahedranes <1998JOM(555)263>. The THF adduct, TsiGaMe2THF, can be isolated in 90% yield from the reaction between TsiLi2THF and Me2GaCl in THF. When the adduct is sublimed the THF is lost to give the solvent-free TsiGaMe2 <1997CEJ1783>, which can also be prepared in 58% yield from the reaction between base-free TsiLi and Me2GaCl <1997ZAAC(623)1455>. If a coordinating group is present in the trisilyllithium substituent, then solvent is excluded from the product; thus, reaction of 40 with GaCl3 generates the gallium analog of 61 in 58% yield <1999OM45>. The reactions between InBr and trisilyllithium reagents as shown in Equation (12) afford oligomers of (RR1MeSi)3CIn, 70 <1995JOM(493)C1, 1998OM5009>. For RR1 = Me2, EtMe, and BunMe the compounds are tetrameric in benzene solution, while for the larger cases of RR1 = MePri and MePh the compounds are monomers in solution. For RR1 = Et2 there is a monomer–dimer equilibrium in solution. In the solid state when RR1 = Me2, EtMe, Et2, or MePri, the compounds are tetrameric, having a near perfect tetrahedral arrangement of indium atoms, similar to the tetrahedral gallium species described previously <1995COFGT(6)377>. In the reaction of TsiLi with InBr an unusual species 71 is also formed in 24% yield, which contains a chain of three indium atoms <2002ZAAC(628)1963>. The tetrahedrane [TsiIn]4 has been used as a convenient source of the monomer TsiIn for the preparation of a variety of organometallic compounds containing TsiIn (see, e.g., <2003OM2705, 2001CEJ4216, 2001IC750, 2000ZAAC(626)2043>). InBr + (RR1MeSi)3C-Li

Toluene, –40 °C

[(RR1MeSi)3CIn]n

70 R = Me, R1 = Me, 69%; R = Me, R1 = Et, 47% R = Me, R1 = Bun, 57%; R = Me, R1 = Pri, 64% R = Me, R1 = Ph, 66%; R = Et, R1 = Et, 56%

ð12Þ

The reaction of In(III) compounds with bulky lithium reagents has also continued to be of interest. Thus, the reaction of InBr3 with TsiLi in THF/Et2O gives a 60% yield of [Li(THF)4][TsiInBr3] <1998ZAAC(624)4> and the reaction of TsiLi with Me2InCl in Et2O gives TsiInMe2 in 65% yield <1997ZAAC(623)1455>. The reaction of base-free TsiLi and InX3 (X = Cl, Br, or I) at 78 C in a 1:1 ratio gives Li[TsiInX3] but if 2 equiv. of TsiLi are used then a methylation occurs to give TsiInMeCl, and if 3 equiv. of TsiLi are used then two methylations occur to give TsiInMe2 together with the 1,3-disilacyclobutane [Me2SiC(SiMe3)2]2 <2001ZAAC(627)715>. If moisture is present in the reaction between TsiLi and Prn2InBr, an unusual hydroxide-bridged trimer, 72, is formed in 28% yield, presumably via hydrolysis of the initially formed TsiInPr2n <1999ZAAC(625)547>. Some of the chemistry described above for gallium and indium can be extended to thallium. The reaction of TsiLi with the thallium(I) organometallic TlCp in a 1:1 ratio gives the deep red-violet TsiTl, which is tetrameric in the solid state having a slightly distorted tetrahedron of thallium atoms similar to that described above for the gallium and indium analogs <1997AG(E)64>.

Functions Containing at Least One Metalloid (Si, Ge, or B) (Me3Si)3C HO (Me3Si)3C In

397

OH In

H Prn O

C(SiMe3)3 In Prn

Prn 72

(e) Three Si and one group 14 metal functions. Compounds containing the Si3MC grouping where M = Sn or Pb are usually made by simple metathesis reactions between trisilyllithium reagents and metal halides. For example, reaction between SnX4 and TsiLi in Et2O at 78 C affords the expected TsiSnX3 compounds in excellent yields, 91% for X = Cl <2002AG(E)1365> and 89% for X = Br <1999EJI869>. However, reaction between (Me3Si)3CLi and SnX4 (where X = Cl, Br, or I) in a 2:1 ratio in toluene solution gives (Me3Si)3C(PhCH2)SnX2 in 58%, 72%, and 76% yields respectively for X = Cl, Br, or I, apparently via a radical mechanism similar to that found in the germanium analog described in Section 6.13.1.1.2 <1999ZAAC(625)1807>. The related bulky reagent, (PhMe2Si)3CLi, reacts with SnCl4 in THF to give only a 25% yield of (PhMe2Si)3CSnCl3 along with (PhMe2Si)3CCl as the main product but it reacts more cleanly with Me2SnCl2 to give (PhMe2Si)3CSnMe2Cl, which reacts readily with EtOH to give the final product (PhMe2Si)3CSnMe2OEt in 76% yield <1998JOM(564)215>. Related reagents that contain substituents capable of intramolecular coordination to the tin atom also undergo similar metathesis reactions. Thus reaction of 40 with SnCl4 gives (Me2NMe2Si)(Me3Si)2CSnCl3, which probably has intramolecular SnN coordination, in 78% yield <1999OM45>, and treatment of (Me2NMe2Si)2(Me3Si)CLi with Me3SnCl gives (Me2NMe2Si)2(Me3Si)CSnMe3 (along with the precursor (Me2NMe2Si)2(Me3Si)CH) <1999JCS(D)3267>. Derivatization using Bu3SnCl of the organometallic reagent formed by metallation of 3 affords a derivative of 5 in which a Bu3Sn group has replaced the SiMe2R group <1998CL1145>. It is likely that a second metallation and further reaction with a tin halide would give a further range of compounds containing two Si3SnC substituted centers. Introduction of two tin atoms occurs in the reaction of the [Li(TMEDA)2] salt of 44 with Me2SnCl2 or the [Li(THF)4] salt of 44 with SnCl4 to afford [ClR2SnC(SiMe3)2SiMe2CH2]2 in 79% and 47% yields, respectively for R = Me and Cl <1999OM2342>. The Si3SnC grouping has also been prepared by using the reaction between a disilylstannyllithium reagent and a silyl chloride. Thus, (Me3Si)2(PhMe2Sn)CLi reacts with Me2SiCl2 to furnish (Me3Si)2(PhMe2Sn)CSiMe2Cl in 76% yield <1998JOM(564)215>. Reactions of (Me3Si)2(PhMe2Sn)CLi (for its synthesis, see Section 6.13.1.3.1) with a range of other metal halides would, no doubt, allow convenient preparation of many new Si2SnMC groupings. The high degree of steric protection afforded by an (R3Si)3C substituent at a group 14 metal center has prompted investigation into the stabilization of M(II) species where M = Sn or Pb by such substituents. Reaction of (Me3Si)2(2-NC5H4Me2Si)CLi with SnCl2 or PbCl2 gives monomeric organotin- and organolead(II) chlorides in 74% and 47% yields, respectively, which have structures analogous to that of the related germanium compound 27 <2001OM1223>. The bis-methoxy species (MeOMe2Si)2Me3SiCLi reacts with SnCl2 to give (MeOMe2Si)2Me3SiCSnCl in 65% yield <1999JCS(D)3267>. The first structurally characterized organometallic ate complex of Sn(II), has a structure similar to that of the germanium analog, 28, and has been prepared in 60% yield from the reaction of (Me3Si)3CLi with Sn(SBun)2 <2002OM4005>. Treatment of the K(THF)2 salt of [CH2(SiMe2)(Me3Si)2C]2 2 (see Section 6.13.1.2.1(a)) with SnCl2 in Et2O at 78 C gives a mixture of dialkyl Sn(II) compounds 73 (M = Sn) and 74, both of which readily undergo oxidative addition reactions to give Sn(IV) compounds <1997OM5621, 2000OM49, 2002OM2183, 2002OM2430>. Chlorobridged dimers 75 are formed from the reaction of (PhMe2Si)3CLi and MCl2 in THF <1995CC1829, 1997OM5653>. The lead species is a yellow-orange solid and is the first monoorganolead(II) derivative to be characterized. In contrast, if the smaller reagent TsiLi reacts with PbCl2 in THF then a chloro-bridged trimer 76 is produced in 85% yield <1997OM5653>. When the organolithium reagent (MeOMe2Si)(Me3Si)2CLi reacts with MCl2, where M = Sn or Pb, intramolecular coordination of the OMe group to the metal occurs to give the four-coordinate M(II) species 77 <1997OM5653>. Treatment of the [Li(TMEDA)2] salt of 44 with PbCl2 gives the Pb(II) organometallic species 73 (M = Pb) as dark blue crystals in 85% yield <1997OM5621>.

398

Functions Containing at Least One Metalloid (Si, Ge, or B) Me2Si (Me3Si)2C

SiMe2 C(SiMe3)2

CH2Me2Si(Me3Si)2CSnCl CH2Me2Si(Me3Si)2CSnCl

M

M (PhMe2Si)3C

74

73, M = Sn or Pb

(Me3Si)3C

Pb Cl

76

Cl

Pb Cl

C(SiMe3)3

Pb C(SiMe3)3

Cl C(SiMe2Ph)3 M Cl

75, M = Sn or Pb SiMe3 Me Me3Si Cl O C SiMe2 M M Me2Si Cl C O SiMe3 Me Me3Si 77, M = Sn, 93%; M = Pb, 60%

(f) Three Si and one transition metal functions. The reaction of lithium reagent 39 with CrCl2 gives a 40% yield of 78 having a square-planar geometry at Cr, together with a small amount of 79 <2000OM3224>. Reaction of TsiLi2THF with CrCl2 is reported to give Tsi2Cr, but no details have been given <2002USP00334829>.

N Me2Si SiMe3 Me3Si C Cr C SiMe3 Me3Si SiMe2 N

N Me2Si Me3Si C Cr Cl SiMe3 Me3Si Cl Cr C SiMe3 N SiMe2

78

79

Reaction of the lithium reagent 39 with MnCl2 gives the manganese complex 80 in 41% yield <2000OM3224>. Similarly, the lithium reagent 40 reacts with 1 equiv. of MnCl2 to give a 95% yield of 81 X = Cl, and with 0.5 equiv. of MnCl2 to give [(Me2NMe2Si)(Me3Si)2C]2Mn in 72% yield together with a small amount of the Mn(III) complex 81 X = O (presumably formed via oxidation by adventitious air) <2002JOM(649)121>. Reaction of the related reagent containing a chelating methoxy group (see Table 2) with MnCl2 gives 82 in 63% yield <2002JOM(649)121> while the use of the chelated dialkyllithium reagent 44 affords the chloride-bridged, high-spin manganese complex 83 in 60% yield <2000OM1190>.

N Me2Si Me3Si C Mn Cl Me3Si Cl

Li(THF)3

80 THF Me (Me3Si)2 C Cl O Me2Si Mn Mn SiMe2 O Cl C (SiMe3)2 Me THF 82

Me2Si NMe2 Me3Si C Mn X SiMe3 Me3Si X Mn C SiMe3 Me2N SiMe2 81, X = Cl, X = O Me2Si (Me3Si)2C

SiMe2 C(SiMe3)2 Mn Cl Li(THF)3 83

Reaction of base-free TsiLi with FeCl3 leads to reduction and formation of the Fe(II) compound Tsi2Fe in 68% yield <2001ZAAC(627)715>. If coordinated THF is present in the lithium reagent, TsiLi2THF, then reaction with FeCl2 at 35 C in THF solution also occurs to give red blocks of Tsi2Fe in 44% yield <2003ICA(345)359, 2002USP00334829>.

399

Functions Containing at Least One Metalloid (Si, Ge, or B)

Reaction of the lithium reagent 39 with CoBr2 gives the halide-bridged ate complex 84 in 56% yield <2000OM3224>. Similarly, lithium reagent 40 containing a dimethylamino substituent capable of acting as a ligand, reacts with CoBr2 to give 85 in 50% yield <2002JOM(649)121>. The simple diorganocobalt compound Tsi2Co has been reported to be formed as dark-green, plate-like crystals from the reaction between CoCl2 and TsiLi2THF but no spectroscopic details are available <2002USP00334829>.

N Me2Si Me3Si C Co Br Me3Si Br Li(THF)2

Me2Si NMe2 Me3Si C Co Br SiMe3 Me3Si Br Co C SiMe3 Me2N SiMe2

84

85

The first -bonded organonickel(I) compound 86 is obtained in 30% yield from the reaction shown in Scheme 4. Trace amounts of hydroxide present in the starting material are thought to be responsible for the formation of complex 87 as a minor by-product. In contrast, reaction of [PdCl2(PPh3)2] gave the chloro-bridged dimer 88 as a pale yellow solid in 53% yield <2000CC691>.

2 [PdCl2(PPh3)2]

N Me2Si Me3Si C Li THF Me3Si

[NiCl2(PPh3)2] THF, –78 °C trace H2O

THF, –78 °C

N

Me3Si

SiMe3 C

SiMe2 Cl Pd Pd Cl C N SiMe3 Me3Si

Me2Si

N Me2Si Me3Si C Ni PPh3 Me3Si 86

88

Me2 SiMe 3 Si C N O SiMe2 Ni Ni O N Me2Si C Si Me3Si Me2 87

Scheme 4

Reaction of 39 with CuI or AuClSMe2 gives dimeric products 89 M = Cu or Au in 62% and 37% yields, respectively <2002JCS(D)2467>. Me2 (Me3Si)2C Si M N M N Si C(SiMe3)2 Me2

89, M = Cu or Au

The reactions between group I metal derivatives of trisilylmethanes and CuCN can give a variety of products. Thus, treatment of CuCN with (PhMe2Si)3CM (M = Li or Na) in THF solution affords the monomeric species (PhMe2Si)3CCuCNM(THF)3 which, when crystallized from toluene, gives the dimeric species 90 <2000OM5780>. Similar dimers, 91 and 92, are formed, in 65% and 41% yield, respectively, directly from reactions with (RMe2Si)(Me3Si)2CLi (R = Me or NMe2) while (MeOMe2Si)2(Me3Si)CLi gives 93 <2002JCS(D)3975>. Crystallization of the product formed from the potassium reagent (PhMe2Si)3CK and CuCN gives the tetramer 94 in 43% yield <2000OM5780>.

400

Functions Containing at Least One Metalloid (Si, Ge, or B) SiMe3

THF Li

THF

THF Li RCu CN NC CuR Li THF THF

Cu

CN

SiMe2

OMe

MeO

Me2Si Me2Si

90, R = (PhMe2Si)3C 91, R = (Me3Si)3C 92, R = (Me2NMe2)(Me3Si)2C

C SiMe2

MeO OMe C

Cu

CN

Me3Si

Li THF

93

K RCu

C

N

K C

RCu

N

N

K

K

C

CuR

94, R = (PhMe2Si)3C

N C CuR

(g) Three Si and one lanthanide or actinide functions. The first structurally characterized -bonded organosamarium(II) complex [Sm{C(SiMe3)2(SiMe2OMe)}2THF] was obtained from the reaction between K{C(SiMe3)2(SiMe2OMe)} and [SmI2(THF)2]. The compound is isolated as deep green-black, air-sensitive crystals in 71% yield and should inspire further work into alkyl, rather than the more well-known cyclopentadienyl, derivatives of samarium <1997AG(E)2815>. Reaction of a range of alkylpotassium species with YbI2 (Equation (13)) in benzene solution gives simple, monomeric dialkylytterbium compounds 95 <1994JA12071, 1996OM4783> including the solvent-free dialkyl lanthanide compound Tsi2Yb as an orange solid in 85% yield which, despite the steric encumbrance of the Tsi groups, is bent at Yb (CYbC angle 137 ) and can act as a polymerization catalyst for methylmethacrylate <2002JOM(647)128, 2003T10409>. A similar metathetical reaction occurs between TsiK and EuI2 to give the bent species Tsi2Eu in 65% yield <1996OM4783>. Grignard-like complexes [RYbIEt2O]2, 96, are formed from the reaction between RI and elemental Yb in Et2O (Equation (14)) <1994JA12071, 1996OM4783>. Reaction of the dipotassium compound 48 with YbI2 in benzene solution affords 97 in 45% yield <1999OM2342>. In contrast to the reactions carried out in benzene as a solvent, reaction between TsiK and YbI2 in Et2O in either a 2:1 or a 1:1 ratio gives the centrosymmetric dimer 98 as orange-red crystals in 63% yield. It is not clear how the EtO group is generated, but possibly by the Lewis acid character of initially formed Tsi2Yb or TsiK cleaving the solvent <1994CC2691, 1995JCS(D)3933>. YbI2 +

2(Me3Si)2(Me2RSi)CK

C6H6

[(Me3Si)2(Me2RSi)C]2Yb + 2KI 95, R = Me, 85% R = CH2=CH, 80% R = EtOCH2CH2, 70%

(Me3Si)2(Me2RSi)CI + Ybpowder

Et2O

Et2O

Yb

(RMe2Si)(Me3Si)2C

C(SiMe3)2(SiMe2R) I Yb I OEt2

96, R = Me R = OMe, 65%

Me2Si (Me3Si)2C

SiMe2 C(SiMe3)2 Yb 97

Et O C(SiMe3)3 Yb Yb O (Me3Si)3C OEt2 Et Et2O

98

No trisilylmethyl derivatives of the actinide elements seem to have been prepared.

ð13Þ

ð14Þ

401

Functions Containing at Least One Metalloid (Si, Ge, or B) (ii) Three Ge and one metal functions

As has been seen in sections above there is a general lack of compounds containing several germanium atoms attached to the same carbon and there do not appear to be any compounds containing the Ge3MC grouping known. Such compounds should be readily available via the routes used to prepare the many analogous Si3MC containing functions as described above.

(iii) Three B functions As has been described above, there are few compounds containing several boron atoms attached to carbon apart from carboranes and other compounds with multicenter bonding. See reference <1995COFGT(6)377> for early work in this field.

6.13.1.2.2

Other mixed metalloid functions

(i) Two Si, one Ge, and one metal functions Treatment of XMe2GeCBr(SiMe3)2 with PhLi (for X = Br) or Bun (for X = OPh) at low temperature gives XMe2GeCLi(SiMe3)2 species which, on warming, eliminates LiX to give the unsaturated Me2Ge¼C(SiMe3)2 <2000CJC1412, 2000JOM(598)304>.

(ii) Two Si, one B, and one metal functions The products obtained from the reaction between boriranylideboranes and [CoCp(C2H4)2] depend on the substituents at boron. For R = duryl (2,3,5,6-Me4C6H) or mesityl the dinuclear metal complexes 99 are formed (in 46% and 19% yields, respectively) but for R = But the mononuclear complex 100 is formed (Scheme 5) in 11% yield <1998CEJ44>. R

R

B B

Me3Si

C

C

Me3Si 2[CoCp(C2H4)2]

2[CoCp(C2H4)2] R = mesityl or duryl Co Me3Si Me3Si

C

R = But

R C B

B

Co Me3Si

Men

Me3Si

Co 99

C

B

But

B But 100

Scheme 5

(iii) One Si, one Ge, one B, and one metal functions. Also two Ge, one Si, and one metal functions. Also two Ge, one B, and one metal functions. Also Two B, one Si, and one metal functions. Also two B, one Ge, and one metal functions Very few examples of compounds containing these functions seem to have been prepared. Compounds containing such functions should, however, be available from synthetic routes described above in this section. In particular, such functions should be available from the reactions between suitably substituted lithium reagents and appropriate metal halides.

402

Functions Containing at Least One Metalloid (Si, Ge, or B)

As would be expected from the ready metallations of trisilylmethane derivatives the digermylsilylmethane (Me3Ge)2(FBut2Si)CH reacts with MeLi in THF/Et2O to give (Me3Ge)2(FBuFBut2Si)CLi, which, when treated with Me3SnCl, affords (Me3Ge)2(FBut2Si)CSnMe3 in 51% yield <1996JOM(511)239>.

6.13.1.3 6.13.1.3.1

Methanes Bearing Two Metalloid and Two Metal Functions Two Si and two metal functions

Metallation of BrMe2SnCBr(SiMe3)2 by PhLi affords BrMe2SnCLi(SiMe3)2 which, when warmed, eliminates LiBr to give first a stannene and then a cyclic dimer, 101, as shown in Scheme 6 <2000JOM(598)292, 2000JOM(598)304>. A related bulky methyllithium derivative (Me3Si)2(PhMe2Sn)CLi was readily prepared via SnC bond cleavage of (Me3Si)2(PhMe2Sn)2C by MeLi in THF/Et2O <1998JOM(564)215>.

Me2Sn C(SiMe3)2 + PhLi Br Br

Et2O

Me2Sn C(SiMe3)2 Br Li

low temp.

Warm

Me2Sn C(SiMe3)2

–LiBr x2 Me2Sn C(SiMe3)2 (Me3Si)2C SnMe2 101

Scheme 6

Attempts have been made to prepare (Me3Si)2CLi2 by the pyrolysis of either the ate complex [Li(THF)4][Tsi2Li] or the solvent-free [TsiLi]2 (a method that works in the synthesis of (Me3Si)2SiLi2 from (Me3Si)3SiLi) but they fail and give instead oligomeric products <1998MI222>.

6.13.1.3.2

Two Ge and two metal functions

There do not appear to be any compounds containing this function but they could, doubtless, be prepared in similar ways to the analogous Si2M2C-containing species described above in Section 6.13.1.3.1.

6.13.1.3.3

Two B and two metal functions

Compounds containing this grouping are relatively rare (see <1995COFGT(6)377> for early work in the area). A range of diboraallenes, 102, containing a four-coordinate planar carbon can be prepared according to Equation (15) from the anions 103 <2001AG(E)2662>. Synthetic approaches to planar carbon atoms have often involved the preparation of compounds containing carbons heavily substituted by metalloids or metals and this work has been reviewed in <1999CSR367>.

R1

– B C B R1

+

2 R2Li

–(Me3Si)2CHLi

(Me3Si)2CH 103

R1 R2

R1 = R2 = mesityl R1 = R2 = 2,3,5,6-Me4C6H R1 = R2 = 2,6,-Me24-ButC6H2 R1 = mesityl, R2 = But

OEt2 Li – R1 – B C B R2 Li OEt2 102

ð15Þ

Functions Containing at Least One Metalloid (Si, Ge, or B) 6.13.1.3.4

403

Other combinations of two metalloids and two metal functions

There are very few compounds known containing mixed metalloids and two metal functions. They should, however, be available by the routes described above for related compounds containing two of the same metalloid. One notable example of this type of compound is racemic (Me3Pb)(Me3Sn)(Me3Ge)(Me3Si)C, a molecule containing all the elements of group 14 connected together, which can be obtained from a series of metathesis reactions .

6.13.1.4

Methanes Bearing One Metalloid and Three Metal Functions

6.13.1.4.1

One Si and three metal functions

Relatively few new compounds of this type have been prepared since those described in <1995COFGT(6)377>. The bulky dialkyltitanium complex 104 reacts with AlMe3 (Equation (16)) to give the four-coordinate carbide complex 105 in 78% yield <2001OM1175>.

Cp Me3 Si

Ti

N

PPr3i

SiMe3

PPr3i 3AlMe3 –3CH4

Cp Me

104

6.13.1.4.2

Ti

N AlMe2 C

+ AlMe2CH2SiMe3

ð16Þ

Al SiMe3 Me2 105

One Ge and three metal functions

No new compounds containing this grouping seem to have been prepared since those described in <1995COFGT(6)377>.

6.13.1.4.3

One B and three metal functions

There seem to be few, if any, compounds of this type known. It may be possible to prepare such species by the reaction of a methylidyne cluster with a borane, R2BH, in a manner similar to that used in the preparation of silyl-substituted alkylidyne complexes.

6.13.2 6.13.2.1

METHANES BEARING FOUR METAL FUNCTIONS Methanes Bearing Four Similar Metals

A slightly modified method for the preparation of (Me3Sn)4C from CCl4, Li, and Me3SnCl has been reported together with new spectroscopic data <1995JOM(496)241>. This compound does not seem to have been of use in synthesis but has been the subject of several detailed structural studies (see, e.g., <1999MI385>). A method for obtaining very pure Hofmann’s base, [CHg4O(OH)2OH2]n, has been described <1996JOM(522)297>. The pure base can be used in the preparation of C(HgNO3)4 and C(HgSO4)2(HgOH2)2.

6.13.2.2

Methanes Bearing Three Similar and One Different Metal Functions

Treatment of phosphinimide complexes 106 with excess AlMe3 leads to multiple CH bond activation and formation of the carbide complexes 107 in good yield (Equation (17)) <2001OM1175>. (For the products from the analogous reaction with bulky alkyl substituents at Ti see Section 6.13.1.4.1, and for their behavior in solution see Section 6.13.3.)

404

Functions Containing at Least One Metalloid (Si, Ge, or B) PR3 PR3 N Cp1 Ti Me Me

Cp1

3AlMe3

AlMe2

ð17Þ

C

Al AlMe2 Me2

1 i 106, Cp = Cp; R = Cy or Pr Cp1 = indenyl; R = Pri

6.13.2.3

Ti

Me

–3CH4

N

107

Methanes Bearing Two Similar and Two Different Metal Functions

Compounds containing this type of grouping seem to be very rare although carbons coordinated by different metals may well occur in metal carbides, these are outside the scope of this chapter.

6.13.2.4

Methanes Bearing Four Different Metal Functions

Although there are a potential 135 751 different combinations (and their optical isomers) of 43 different metals at a tetrahedral carbon center, very few seem to have been prepared. A comprehensive search of the literature for such a large number of functional groups is clearly very difficult to carry out and it is quite possible that many such groupings have been missed in compiling this article. It is hoped that any omissions of such groupings will not be serious for the organic chemist.

6.13.3

METHANES BEARING MORE THAN FOUR METALLOID OR METAL FUNCTIONS

Polyhedral metallacarboranes in which carbon is bonded to more than four metalloid or metal centers via multicenter interactions are numerous but beyond the scope of this article. Reviews of metallacarborane chemistry can be found in <2002CCC728, 2002CCR(231)23, 2000MCLC(342)7, 1999JOM(581)1>. Variable temperature NMR studies show that the four-coordinate carbide complexes, 107 (see Section 6.13.2.2), are in equilibrium (Equation (18)) with five-coordinate complexes 108 in the presence of AlMe3 <2000AG(E)3263>. Cp

PR3 Cp

Ti

Me

N AlMe2

C Al AlMe2 Me2

AlMe3 –AlMe3

Me Me2Al

PR3 Me2 N Al

Ti C

Me

ð18Þ

Al Me2

107 R = Pri or Ph

AlMe2

108

ACKNOWLEDGMENTS This chapter is dedicated to Professor C. Eaborn, FRS, who died in February 2004. Much of the chemistry described above was initiated in the Eaborn group and the versatility of reagents, such as (Me3Si)3CLi, that have now become popular across a wide range of organometallic chemistry was demonstrated first in the research laboratories at Sussex University.

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Schno¨ckel, J. Am. Chem. Soc. 2000, 122, 9178. A. Pepels, H. Guenther, J.-P. Amoureux, C. Fernandez, J. Am. Chem. Soc. 2000, 122, 9858. A. G. Avent, D. Bonafoux, C. Eaborn, M. S. Hill, P. B. Hitchcock, J. D. Smith, J. Chem. Soc., Dalton Trans. 2000, 2183. W. Uhl, M. Benter, J. Chem. Soc., Dalton Trans. 2000, 3133. C. Eaborn, S. M. El-Hamruni, M. S. Hill, P. B. Hitchcock, A. LeGouic, J. D. Smith, J. Organomet. Chem. 2000, 597, 3. K. D. Safa, M. G. Asadi, A. Abri, A. Mohammadpour, H. Kiae, J. Organomet. Chem. 2000, 598, 222. N. Wiberg, T. Passler, S. Wagner, K. Polborn, J. Organomet. Chem. 2000, 598, 292. N. Wiberg, T. Passler, S. Wagner, J. Organomet. Chem. 2000, 598, 304. M. Shimizu, T. Hiyama, M. Matsubara, T. Yamabe, J. Organomet. Chem. 2000, 611, 12. N. S. Hosmane, J. A. Maguire, J. Organomet. Chem. 2000, 614, 10. R. N. Grimes, Mol. Cryst. Liq. Cryst. 2000, 342, 7. C. Eaborn, M. S. Hill, P. B. Hitchcock, D. Patel, J. D. Smith, S. Zhang, Organometallics 2000, 19, 49. L.-K. Liu, L.-S. Luh, Organometallics 2000, 19, 374. C. Eaborn, P. B. Hitchcock, J. D. Smith, S. Zhang, W. Clegg, K. Izod, P. O’Shaughnessy, Organometallics 2000, 19, 1190. S. S. Al-Juaid, C. Eaborn, P. B. Hitchcock, M. S. Hill, J. D. Smith, Organometallics 2000, 19, 3224. C. Eaborn, M. S. Hill, P. B. Hitchcock, J. D. Smith, Organometallics 2000, 19, 5780. K. D. Safa, A. R. Koushki, M. G. Asadi, Phos. Sulf. Silicon 2000, 158, 97. T. Viefhaus, A. Walz, M. Niemeyer, W. Schwarz, J. Weidlein, Z. Anorg. Allg. Chem. 2000, 626, 2040. W. Uhl, S. Melle, Z. Anorg. Allg. Chem. 2000, 626, 2043. A. Schnepf, R. Ko¨ppe, H. Schno¨ckel, Angew. Chem., Int. Ed. Engl. 2001, 40, 1241. Y. Sahnin, M. Hartmann, G. Geiseler, D. Swiekart, C. Balzerit, G. Frenking, W. Massa, A. Berndt, Angew. Chem., Int. Ed. Engl. 2001, 40, 2662. W. Uhl, S. Melle, Chem. -Eur. J. 2001, 7, 4216. A. Ziegler, H. Pritzkow, W. Siebert, Eur. J. Inorg. Chem. 2001, 387. K. Schmohl, H. Reinke, H. Oeme, Eur. J. Inorg. Chem. 2001, 481. W. Uhl, S. Melle, G. Frenking, M. Hartmann, Inorg. Chem. 2001, 40, 750. C. Ackerhans, P. Bottcher, P. Muller, H. W. Roesky, I. Uson, H.-G. Schmidt, M. Noltemeyer, Inorg. Chem. 2001, 40, 3766.

Functions Containing at Least One Metalloid (Si, Ge, or B) 2001JA994 2001JCS(D)1541 2001JCS(D)3397 2001JOM(620)127 2001JOM(631)76 2001JOM(640)29 2001MI(162)225 2001OM1175 2001OM1223 2001OM2047 2001ZAAC(627)715 2002AG(E)1365 2002AG(E)3829 2002CCC728 2002CCC869 2002CCR(231)23 2002CCR(232)173 2002JCS(D)2467 2002JCS(D)3971 2002JCS(D)3975 2002JOM(647)128 2002JOM(649)121 2002OM2183 2002OM2430 2002OM4005 2002USP00334829 2002ZAAC(628)1963 2003AG(E)669 2003AG(E)671 2003ICA(345)359 2003JA7534 2003OM2505 2003OM2705 2003T10409 2004JOM(689)1238 2004JOM(689)1718

407

Z.-X. Wang, P. v. R. Schleyer, J. Am. Chem. Soc. 2001, 123, 994. C. Eaborn, J. D. Smith, J. Chem. Soc., Dalton Trans. 2001, 1541. C. Eaborn, J. Chem. Soc., Dalton Trans. 2001, 3397. E. J. Hawrelak, D. Sata, F. T. Lapido, J. Organomet. Chem. 2001, 620, 127. S. S. Al-Juaid, A. G. Avent, C. Eaborn, S. M. El-Hamruni, S. A. Hawkes, M. S. Hill, M. Hopman, P. B. Hitchcock, J. D. Smith, J. Organomet. Chem. 2001, 631, 76. C. Eaborn, A. Kowalewska, J. D. Smith, W. A. Stan´czyk, J. Organomet. Chem. 2001, 640, 29. M. Schormann, K. S. Klimek, H. Hatop, S. P. Varkey, H. W. Roesky, C. Lehman, C. Ro¨pken, R. Herbst-Irmer, M. Noltemeyer, J. Solid State Chem. 2001, 162, 225. J. E. Kickham, F. Gue´rin, J. C. Stewart, E. Urbanska, D. W. Stephan, Organometallics 2001, 20, 1175. S. S. Al-Juaid, A. G. Avent, C. Eaborn, M. S. Hill, P. B. Hitchcock, D. J. Patel, J. D. Smith, Organometallics 2001, 20, 1223. K. S. Klimek, J. Prust, H. W. Roesky, M. Noltemeyer, H.-G. Schmidt, Organometallics 2001, 20, 2047. T. Viefhaus, W. Schwarz, K. Hubler, K. Locke, J. Weidlein, Z. Anorg. Allg. Chem. 2001, 627, 715. J. Janssen, J. Magull, H. W. Roesky, Angew. Chem., Int. Ed. Engl. 2002, 41, 1365. W. W. du Mont, T. Gust, E. Seppa¨la¨, C. Wismach, P. G. Jones, L. Ernst, J. Grunenberg, H. C. Marsmann, Angew. Chem., Int. Ed. Engl. 2002, 41, 3829. R. N. Grimes, Coll. Czech. Chem. 2002, 67, 728. A. Franken, C. A. Kilner, M. Thornton-Pett, J. D. Kennedy, Coll. Czech. Chem. 2002, 67, 869. Z. Xie, Coord. Chem. Rev. 2002, 231, 23. J. F. Valliant, K. J. Guenther, A. S. King, P. Morel, P. Schaffer, O. O. Sogbein, K. A. Stephenson, Coord. Chem. Rev. 2002, 232, 173. C. Eaborn, M. S. Hill, P. B. Hitchcock, J. D. Smith, J. Chem. Soc., Dalton Trans. 2002, 2467. A. G. Avent, C. Eaborn, I. B. Gorrell, P. B. Hitchcock, J. D. Smith, J. Chem. Soc., Dalton Trans. 2002, 3971. C. Eaborn, S. M. El-Hamruni, M. S. Hill, P. B. Hitchcock, J. D. Smith, J. Chem. Soc., Dalton Trans. 2002, 3975. H. Yasuda, J. Organomet. Chem. 2002, 647, 128. S. S. Al-Juaid, C. Eaborn, S. M. El-Hamruni, P. B. Hitchcock, J. D. Smith, S. E. So¨zerli, J. Organomet. Chem. 2002, 649, 121. A. Asadi, A. G. Avent, C. Eaborn, M. S. Hill, P. B. Hitchcock, M. M. Meehan, J. D. Smith, Organometallics 2002, 21, 2183. A. Asadi, C. Eaborn, M. S. Hill, P. B. Hitchcock, M. M. Meehan, J. D. Smith, Organometallics 2002, 21, 2430. I. V. Borisova, C. Eaborn, M. S. Hill, V. N. Khrustalev, M. G. Kuznetzova, J. D. Smith, Y. A. Ustynyuk, V. V. Lunin, N. N. Zemlyansky, Organometallics 2002, 21, 4005. Hall, K.; Murphy, V.; Lapointe, A. M.; Van Beek, J. A. M.; Diamond, G. M. U.S. Patent 200200334829; CAN 136, 263 599. W. Uhl, F. Schmock, G. Gieseler, Z, Anorg. Allg. Chem. 2002, 628, 1963. Y. Sahin, C. Prasang, P. Amseis, M. Hofmann, G. Geiseler, W. Massa, A. Berndt, Angew. Chem., Int. Ed. Engl. 2003, 42, 669. Y. Sahin, C. Prasang, M. Hofmann, G. Subramaniam, G. Geiseler, W. Massa, A. Berndt, Angew. Chem., Int. Ed. Engl. 2003, 42, 671. A. M. LaPointe, Inorg. Chim. Acta 2003, 345, 359. K. Izod, S. T. Liddle, W. Clegg, J. Am. Chem. Soc. 2003, 125, 7534. F. Antolini, P. B. Hitchcock, M. F. Lappert, X.-H. Wei, Organometallics 2003, 22, 2505. C. Gemel, T. Steinke, D. Weiss, M. Cokoja, M. Winter, R. A. Fischer, Organometallics 2003, 22, 2705. G. Qi, Y. Nitto, A. Saiki, T. Tomohiro, Y. Nakayama, H. Yasuda, Tetrahedron 2003, 59, 10409. A. Asadi, A. G. Avent, M. P. Coles, C. Eaborn, P. B. Hitchcock, J. D. Smith, J. Organomet. Chem. 2004, 689, 1238. D. Azarifar, M. P. Coles, S. M. Al-Hamruni, C. Eaborn, P. B. Hitchcock, J. D. Smith, J. Organomet. Chem. 2004, 689, 1718.

408

Functions Containing at Least One Metalloid (Si, Ge, or B) Biographical sketch

Paul D. Lickiss was born in Kent, the Garden of England, studied at The University of Sussex, where he obtained a B.Sc. degree in 1980 and his D.Phil. in 1983 under the supervision of Professor C. Eaborn, FRS. After staying at the University of Toronto with Professor Adrian Brook from 1983 to 1984, he returned to Sussex and took up a position as a Royal Society 1983 University Research Fellow in 1985. In 1989 he resigned his Fellowship to take up a position as a lecturer in the University of Salford where he stayed for four years. From the 1990s, he has been a Lecturer, Senior Lecturer, and now Reader in organometallic chemistry in the Synthesis Section in the Chemistry Department at Imperial College, London. His research interests are mainly in the field of organosilicon chemistry, particularly the synthesis of low-coordinate compounds such as silyl cations and the use of bulky groups to stabilize unusual compounds. He is also interested in the synthesis and uses of organosilanols, especially those containing several Si–OH groups. The use of ultrasound for synthesis is also actively pursued.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 381–408

6.14 Functions Containing a Carbonyl Group and at Least One Halogen R. MURUGAN and S. V. YARLAGADDA Reilly Industries Inc., Indianapolis, IN, USA 6.14.1 INTRODUCTION 6.14.2 CARBONYL HALIDES WITH TWO SIMILAR HALOGENS 6.14.2.1 Carbonic Difluoride 6.14.2.2 Carbonic Dichloride 6.14.2.2.1 Preparation of phosgene 6.14.2.2.2 Phosgene alternatives 6.14.2.3 Carbonic Dibromide 6.14.2.4 Carbonic Diiodide 6.14.3 CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS 6.14.3.1 One Fluorine and Chlorine, Bromine, or Iodine 6.14.3.1.1 Carbonic chloride fluoride 6.14.3.1.2 Carbonic bromide fluoride 6.14.3.1.3 Carbonic fluoride iodide 6.14.3.2 One Chlorine and Bromine or Iodine 6.14.3.2.1 Carbonic bromide chloride 6.14.3.2.2 Carbonic chloride iodide 6.14.3.3 One Bromine and Iodine 6.14.3.3.1 Carbonic bromide iodide 6.14.4 CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHER HETEROATOM 6.14.4.1 One Halogen and One Oxygen 6.14.4.1.1 Fluoroformate esters 6.14.4.1.2 Chloroformate esters 6.14.4.1.3 Bromoformate esters 6.14.4.1.4 Iodoformate esters 6.14.4.2 One Halogen and One Sulfur 6.14.4.2.1 Fluorothiolformate esters 6.14.4.2.2 Chlorothiolformate esters 6.14.4.2.3 Bromothiolformate esters 6.14.4.2.4 Iodothiolformate esters 6.14.4.3 One Halogen and One Nitrogen 6.14.4.3.1 Carbamoyl fluorides 6.14.4.3.2 Carbamoyl chlorides 6.14.4.3.3 Carbamoyl bromides 6.14.4.3.4 Carbamoyl iodides 6.14.4.4 One Halogen and One Phosphorus 6.14.4.4.1 Chlorocarbonyl derivatives of phosphorus(III) 6.14.4.4.2 Chlorocarbonyl derivatives of phosphorus(V) 6.14.4.5 One Halogen and One Arsenic, Antimony, or Bismuth 6.14.4.6 One Halogen and One Metalloid (Boron, Silicon, or Germanium) 6.14.4.7 One Halogen and One Metal 6.14.4.7.1 Halocarbonyl complexes of first transition metal series (iron and chromium) 6.14.4.7.2 Halocarbonyl complexes of second transition metal series (ruthenium and rhodium) 6.14.4.7.3 Halocarbonyl complexes of third transition metal series (rhenium and iridium)

409

410 410 410 411 411 411 412 412 413 413 413 413 414 414 414 414 414 414 414 414 415 415 419 419 419 419 420 420 420 420 421 421 422 422 422 422 423 423 423 424 424 424 424

410 6.14.1

Functions Containing a Carbonyl Group and at Least One Halogen INTRODUCTION

The literature search was done using the general term carbonyl halides and other specific compounds such as carbonyl difluoride, phosgene, chloroformates, etc., discussed by name in this chapter. As observed by the authors, of COFGT (1995) <1995COFGT(6)407>, the present authors observed more literature on those compounds, when the halogen is chlorine. For example, there are more references on carbonyl dichloride than those on carbonyl difluoride, carbonyl dibromide, and carbonyl diiodide combined. Similarly in the case of halo formate derivatives there are more references on chloro formates than those on, fluoro-, bromo-, or iodo-formates. The arrangement of sections and subsections is similar to that of COFGT (1995) <1995COFGT(6)407>, except some sections are not repeated as not much has changed between then and the end of 2003. For example, the section on toxicity and handling of phosgene is not repeated here. In the decade up to 2003, the trend has been towards the ‘‘green chemistry’’ concept of alternative synthetic approaches for the titled functional groups that would replace toxic substances like carbon monoxide and phosgene with other relatively less/nontoxic chemicals like carbon dioxide.

6.14.2

CARBONYL HALIDES WITH TWO SIMILAR HALOGENS

The general preparations reported in <1995COFGT(6)407> on these carbonyl difluoride, dichloride, dibromide, and diiodide are summarized in Scheme 1. There are three general synthetic routes for these compounds. One of the methods is by halogen exchange reaction on carbonyl chloride or phosgene using a halide source. The other two methods start from carbon monoxide and halogen (carbon monoxide insertion into halogens works well for carbonyl difluoride and dichloride), and oxidation of a perhalogenated organic compound with an oxygen oxidant (works well for carbonyl dibromide). X2

CO

COX2

Oxidant

CX4

2X– COCl2

Scheme 1

6.14.2.1

Carbonic Difluoride

A novel approach to making carbonyl difluoride has been to react carbon dioxide and fluorine gas (Equation (1)). This method does not use toxic compounds such as phosgene and carbon monoxide. Carbon dioxide and fluorine are allowed to react with each other in the gaseous state, to produce carbonyl difluoride, at a preferred temperature range of 150–250 C with a mole ratio of 0.5:2, and near atmospheric pressure in a fluorine resistant metal, such as stainless steel, under anhydrous conditions <1999JAP11116216>. CO2

+

F2

COF2

ð1Þ

Carbonyl difluoride has been used in the synthesis of fluorinated methyl ethers <1995USP5382704> of the formula R2CHOCF2A where A is Cl or F, and each R is H, (CF2)nCl, (CF2)nF, or (CF2)nH (where n = 1–10). Dry etching of high-melting-point metals has been achieved by using carbonyl compounds, specifically that of carbonyl difluoride <1995JAP07221074>. This process has been useful for forming electrodes, circuits, etc.

Functions Containing a Carbonyl Group and at Least One Halogen 6.14.2.2

411

Carbonic Dichloride

Carbonic dichloride or carbonyl dichloride or phosgene is the most important of all the functional compounds mentioned in this chapter. It is made commercially in large quantities and almost all the other functional groups mentioned in this chapter could be obtained by chemical transformations on phosgene. Phosgene is also a highly toxic and very reactive compound. It is an industrially important compound, as it is used in the preparation of polyurethanes and polycarbonates. Hence, it is the most studied of all the functional groups mentioned in this chapter. In the early 2000s, there is an awareness that phosgene should be replaced by other less toxic chemicals in the synthesis of polyurethanes and polycarbonates.

6.14.2.2.1

Preparation of phosgene

In general, phosgene has been prepared in three ways: the classical synthesis of insertion of carbon monoxide to chlorine; the chemical as well as photochemical oxidation of perchlorinated compounds; and the decomposition of other phosgene derivatives such as chloroformates and carbonates which are also used as phosgene alternatives. All these methods have been discussed in COFGT (1995) <1995COFGT(6)407>. Phosgene is also produced as one of the products in the photocatalytic degradation of perhalogenated hydrocarbons on porous titanium oxide <2001AC(B)109, 2002MI412>. A report on the synthesis of phosgene from triphosgene or bis(trichloromethyl)carbonate, along with the comparison of the reactivity of phosgene with that of diphosgene and triphosgene with methanol, has been published <2000JOC8224>. Phosgene can be manufactured from diphosgene and triphosgene using deactivated amines as the catalysts. The amine catalysts are selected from poly(2-vinylpyridine), phenanthridine, phthalocyanines, and metallophthalocyanines free and on a polymer support, and poly(N,N-dimethylaminomethylstyrene) <1999GEP19740577>. There are a few reports of carbon labeled phosgene synthesis, which were also discussed in COFGT (1995) <1995COFGT(6)407>. Even in the preparation of 11C-labeled phosgene to make 11C-labeled ureas and isocyanates, alternatives like 11C-labeled carbon dioxide have been used <1999MI537>. Another example of the use of 11C-carbon monoxide in place of labeled phosgene is in the preparation of 11C-carbamoyl compounds using selenium <2002JOC3687>. 11 C-Phosgene, a useful precursor for labeling several radiopharmaceuticals, is generally made by catalytic oxidation of 11C-carbon tetrachloride over iron granules, although in low yields or with poor reproducibility. Chlorination of 11C-methane followed by reaction with a stream of 98:2 nitrogen/oxygen over iron has provided 11C-phosgene <2001MI785>. The yield of 11C-phosgene was significantly increased by using iron oxide along with iron granules <2002MI345>. A simple review of the history, preparation, and uses of phosgene was done by Senet <1998MI12>. A modified production of phosgene from carbon monoxide and chlorine has been patented. This patent claims the use of a metal halide catalyst preferably selected from group III metals like aluminum and gallium <1999GEP19916856>. An improved method for the preparation of phosgene in the laboratory has been reported. In this approach phosgene was prepared by addition of 95–98% sulfuric acid to a mixture of phosphorus pentoxide and carbon tetrachloride <1998MI123>. An interesting way to address the toxicity and safety issues associated with phosgene is the use of a microfabricated reactor for its manufacture. This is an example of the potential for safe on-site/on-demand production of a hazardous compound, in this case phosgene. Complete conversion of chlorine is observed for a 1:1 feed at 8 cc/min, which gives a projected productivity of approximately 100 kg/year from a 10-channel microreactor, with the opportunity to produce significant quantities by operating many reactors in parallel <2001MI1639>.

6.14.2.2.2

Phosgene alternatives

Because of the toxicity and the high reactivity of phosgene, many alternatives have been made and used as phosgene equivalents. Interestingly, most of them are made from phosgene but are easier to handle than phosgene itself. The most common phosgene alternatives mentioned in COFGT (1995) <1995COFGT(6)407> are summarized in Scheme 2.

412

Functions Containing a Carbonyl Group and at Least One Halogen N O

N N

Imidazole

COCl2

Methanol

Phosgene

CH3OCOCl

Methanol CH3OCOOCH3 Cl2

Cl2

N CCl3OCOCl

CCl3OCOOCCl3

Diphosgene

Triphosgene

Scheme 2

Ureas have been traditionally synthesized by methodologies mainly based on the use of dangerous reagents such as phosgene and isocyanates. However, in the late 1990s and early 2000s, these reagents have been increasingly substituted by cleaner and inherently safer compounds, referred to as phosgene substitutes, such as bis(4-nitrophenyl)carbonate, triphosgene, di-t-butyl-dicarbonate, 1,1-carbonylbisimidazole, 1,1-carbonylbisbenzotriazole, S,S-dimethyl dithiocarbonate, and trihaloacetyl chlorides. These safer reagents could be stored and handled without special precautions <2000GC140>. Phosgene has been replaced with carbon dioxide in the synthesis of alkyl carbonates. Mixed or symmetrical dialkyl carbonates were generated in high yields (53–97%) from alcohols, carbon dioxide, and alkyl chlorides in apolar aprotic solvents using guanidine bases under mild conditions <1995JOC6205>.

(i) Prepared from phosgene The common phosgene alternatives are usually made from phosgene, replacing either one or both of the chlorine atoms with a leaving group, and thus making the whole compound more stable and easier to handle. There are also reviews on the use of these phosgene alternatives. For example, the use of bis(trichloromethyl)carbonate or triphosgene in organic synthesis as a substitute for phosgene is well reviewed <1996S553, 1994MI357>. The preparation of N,N0 -carbonyldiimidazole has been reported, starting from imidazole and phosgene. Reaction of imidazole with phosgene in toluene in the presence of tributylamine gave 76% yield of N,N0 -carbonyldiimidazole <2001MI33>.

6.14.2.3

Carbonic Dibromide

Carbon monoxide and bromine are reacted over activated carbon to give carbonyl dibromide (Equation (2)). Like phosgene, carbonyl dibromide is also used in the synthesis of compounds such as diaryl carbonates <1992EUP520238>. In the application on the use of carbonyl dibromide in the preparation of diaryl carbonates, aluminum trifluoride has been used as the catalyst <1992EUP516355>. Carbonyl dibromide is also used in the synthesis of metal bromides and their bromide oxides <1997JCS(D)257>. This reaction of carbonyl bromide with metal oxides is further discussed in Section 6.14.4.7 on the halocarbonyl metal compounds. Activated “C” CO

6.14.2.4

+

Br2

COBr2

ð2Þ

Carbonic Diiodide

This compound was not reported in COFGT (1995) <1995COFGT(6)407> and many attempts to make this compound have failed. It was suggested that this may be due to its poor stability. However, it has been found that heating carbon tetraiodide in a stream of oxygen results in the formation of carbonyl diiodide, and this has been confirmed from its infrared (IR) spectrum (Equation (3)) <1995CPL594>. Carbonyl diiodide, which is similar to carbonyl difluoride, has

Functions Containing a Carbonyl Group and at Least One Halogen

413

been used in the decontamination of metal surfaces that are contaminated by metal oxides of U, Pu, Np, Tc, etc. The metal oxides are converted into their iodides or carbonyl complexes, which are volatile and hence removed by vacuum <2001JAP153996>. CI4

6.14.3

O2

+

ð3Þ

COI2

CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS

The general syntheses of these compounds mentioned in COFGT (1995) are summarized in Scheme 3 <1995COFGT(6)407>. The two major approaches are: the insertion of carbon monoxide with the mixed halogen compound, and halogen exchange with a halide ion source on a carbonyl dihalide with a different halogen. X1X2

X1–

COX1X2

CO

COCl2

–Cl–

Scheme 3

6.14.3.1 6.14.3.1.1

One Fluorine and Chlorine, Bromine, or Iodine Carbonic chloride fluoride

An improved method for the synthesis of carbonyl chloride fluoride under mild conditions has been reported. Pure carbonyl chloride fluoride can be isolated in essentially quantitative yield from the decomposition of the oxygen-bridged COCl2SbF5 donor–acceptor adduct at room temperature (rt) in a dynamic vacuum <1999JFC(94)107> (Equation (4)). These adducts along with that of carbonyl chloride fluoride and penta fluoro compounds have been studied using vibrational spectroscopy, nuclear magnetic resonance (NMR), mass spectra, and theoretical calculations <1997JCS(D)251, 1999IC3143>. COCI2.SbF5

+

COClF

O2

ð4Þ

Carbonyl chloride fluoride is formed by thermal decomposition of chlorofluoro carbons like CCl2F2 with titanium dioxide catalyst <1995JCA394> (Equation (5)), as well as by dielectric discharge <1999MI627>. They are also formed by the oxidation of chlorofluoro carbons with ozone <1992JPC8069> (Equation (6)). CF2Cl2

+

TiO2

O2

CFCl3

+

COFCl

+

O3

Other products

ð5Þ

COFCl

ð6Þ

Carbonyl chloride fluoride is also formed in the oxidation of hydrofluorocarbons with either chlorine <1993MI179> or other oxidants <1993MI(66)97> (Equation (7)). CHFCl2

6.14.3.1.2

+

Cl.

Air

COFCl

Air

Cl.

+

H3CCFCl2

ð7Þ

Carbonic bromide fluoride

Photooxidation of tribromofluoromethane in an oxygen atmosphere containing ozone showed the formation of carbonyl bromide fluoride (Equation (8)) <1996JPC9271>. This compound like other different carbonyl dihalides has been spectroscopically studied, specifically its NMR and mass spectra <1997JCS(D)251>.

414

Functions Containing a Carbonyl Group and at Least One Halogen CFBr3

6.14.3.1.3

O3

+

ð8Þ

COFBr

Carbonic fluoride iodide

The synthesis of carbonic fluoride iodide was reported in COFGT (1995) <1995COFGT(6)407> by a reaction of iodine pentafluoride with carbon monoxide under pressure, and no new synthetic methods for this compound have been reported, up to 2003.

6.14.3.2

One Chlorine and Bromine or Iodine

6.14.3.2.1

Carbonic bromide chloride

Carbonyl bromide chloride has been prepared by the insertion reaction of carbon monoxide with bromine chloride <1993USP5235000>, a readily available brominating reagent (Equation (9)) <1999JPC2624>. BrCl

+

CO

ð9Þ

COBrCl

Carbonyl bromide chloride has also been prepared by the photochemical oxidation of bromochlorohydrocarbons such as, dibromochloromethane and bromodichloromethane, with ozone (Equation (10)) <1999JCS(D)73, 1997JPC2074>. HCBr2Cl + O3

COBrCl + Others

O3 + H2CBrCl

ð10Þ

Like other carbonyl dihalides, carbonyl bromide chloride has been studied for its spectral behavior, like that of NMR and mass spectra <1997JCS(D)251>.

6.14.3.2.2

Carbonic chloride iodide

As was the case in COFGT (1995) <1995COFGT(6)407>, carbonic chloride iodide has not yet (in late 2003) been reported.

6.14.3.3

One Bromine and Iodine

6.14.3.3.1

Carbonic bromide iodide

As in COFGT (1995) <1995COFGT(6)407>, no synthetic method for this compound, carbonic bromide iodide, has been reported, up to the end of 2003.

6.14.4

6.14.4.1

CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHER HETEROATOM One Halogen and One Oxygen

The general methods used for the syntheses of these haloformate esters, reported in COFGT (1995), are summarized in Scheme 4 <1995COFGT(6)407>. The three possible approaches are: first, the nucleophilic displacement of one of the halogen of a dihalo carbonyl with an alcohol to give the haloformates; second, the insertion of carbon monoxide on organo hypohalites; and third, the halogen exchange reaction of one haloformate ester to another haloformate ester by using a halide ion source.

Functions Containing a Carbonyl Group and at Least One Halogen COX2

ROH

ROCl

ROCOX

–HX

415

CO

X1–

ROCOX1 +

X–

Scheme 4

6.14.4.1.1

Fluoroformate esters

A method for the production of aliphatic fluoroformates, where carbonyl fluoride is esterified with aliphatic alcohols (e.g., t-butanol) in an ether at 20 C to +50 C, is described. The method is carried out using carbonyl fluoride obtained by reacting phosgene with surplus powdered sodium fluoride whose granules have a specific surface of 0.1 m2 g1 and/or an average diameter of 20 mm. This method enables the preparation of unstable fluoroformates (e.g., t-Bu fluoroformate) in excellent yields (Equation (11)) <2000WOP0059859>.

OH

+

COCl2

NaF

ð11Þ OCOF

One of the fluoroformates, 9-fluorenylmethyl fluoroformate, is a useful reagent for the largescale synthesis of dipeptide-free Fmoc (9-fluorenylmethoxycarbonyl) amino acids. 9-Fluorenylmethyl fluoroformate (Fmoc-F) is an inexpensive and effective reagent, which is available in large quantities for the synthesis of Fmoc-amino acids <1998MI244>.

6.14.4.1.2

Chloroformate esters

Next to phosgene, chloroformate esters are the most important industrial compounds considered in this chapter. Significant research has been done on the transformation of these compounds into other compounds. Chloroformates are much easier to handle than phosgene and the difference in reactivity of the two leaving groups has been exploited in its chemistry. Diphosgene or trichloromethyl chloroformate, a versatile reagent in organic synthesis, is reviewed. Its reactions with amines, alcohols, and others have been discussed <1992MI230>. Similarly, another chloroformate, methyl chloroformate, has been reviewed for its chemistry as well as its hazardous nature <1994MI181>. As mentioned earlier, because of its importance as an industrial chemical, procedures for the storage and transport of chloroformate esters with reduced decomposition are well documented and regulated. For example, using polymer surface coatings of polyethylene for storage vessels as well as transport pipes decreases the decomposition of ethyl chloroformate <2002GEP10102807>. Chloroformates with the simplest alkyls, such as methyl, ethyl, or isobutyl, are used as general derivatizing agents in gas chromatography. The use of chloroformates in this regard in various disciplines has been reviewed <1998JC57>. The preparation and application of chloroformates, for the immobilization of enzymes, have been described <1995ANY391>.

(i) From phenols and phosgene A continuous process is reported for the preparation of monofunctional aromatic chloroformates. Thus para-cumylphenol in methylene chloride reacted with phosgene in the presence of excess of aqueous sodium hydroxide gave a very good yield of the chloroformate with trace amounts of the diaryl carbonate impurity <2000WOP0058259> (Equation (12)). Other similar approaches are also known <2001WOP0132598, 1994JAP06135900, 1994USP5332841, 1993RUP1240016, 1993RUP1235148, 1996EUP743298, 2000WOP0051964>.

416

Functions Containing a Carbonyl Group and at Least One Halogen O OH Cl

O

NaOH

ð12Þ

COCl2

+

Synthesis and application of 3,5-di-t-butylbenzyl chloroformate for the protection of amino functions and the improvement of solubility in polyurethane synthesis have been reported <1999JPR29> (Equation (13)). O OH +

COCl2

NaOH

O

Cl

ð13Þ

Arylene bis(chloroformates), precursors for cyclic oligomeric carbonate monomers, are prepared by three methods: using PhNEt2 to scavenge HCl, by low pH, low-temperature interfacial condensation of bisphenols with phosgene, and using Ca(OH)2 in interfacial condensation with phosgene <1995MI179> (Equation (14)). O OH

Cl

O +

2COCl2

OH

AIBN

ð14Þ O

Cl O

Chiral resolution of 1,10 -binaphthalene-2,20 -diol and its ()-menthyl chloroformate derivatives by high-performance liquid chromatography has been reported using the urea derivative as a chiral stationary phase <2002MI217>.

(ii) From alcohols and phosgene Chloroformates are prepared by dissolution of water-soluble alcohols having a melting point 20 C in H2O and reaction with phosgene. Trimethylolpropane reacted with phosgene in H2O under ice cooling for 1 h to give 72% trimethylolpropane trischloroformate <2000JAP273066> (Equation (15)). CH2OH CH2OH CH2OH

CH2OCOCl +

3COCl2

CH2OCOCl CH2OCOCl

ð15Þ

Chloroformates are prepared by treating alcohols with molecular sieves followed by reaction with phosgene. Thus, s-butyl alcohol was treated with molecular sieves at room temprature for 15 h, and reacted with phosgene to give 96% s-butyl chloroformate <1999JAP11302230> (Equation (16)). + OH

ð16Þ

COCl2 OCOCl

Chloroformates have also been prepared by phosgenation of alcohols under pressure <1999WOP9911597>, under reduced pressure <2002EUP1216983>, as well as in the presence of activated carbon <1999GEP19737329>. Under the reduced pressure conditions, phosgene has been replaced by either diphosgene or triphosgene <2002EUP1216983>.

Functions Containing a Carbonyl Group and at Least One Halogen

417

Hydroxyalkyl (meth)acrylate chloroformates are prepared by reaction of hydroxyalkylated acrylate or methacrylate esters with chloroformylation agents in the presence of H2O. 2-Hydroxyethyl methacrylate was treated with COCl2 in the presence of H2O at 0 C for 2 h to give 78% chloroformate <1998JAP10130205> (Equation (17)). CH3 +

O

COCl2

OH

O

CH3

NaOH

O O

ð17Þ OCOCl

Purification of methacryloyl-terminated chloroformates is done in high yields by mixing them with hydrocarbon solvents and removing polymerized product by filtration <2001JAP288145>. A convenient process for the synthesis of glyoxylate-derived chloroformates has been developed. The approach involves the reaction of glyoxylate esters with triphosgene and pyridine in various solvent systems. These novel glyoxylate-derived chloroformates are multifunctional, possessing a chloroformate, ester, and haloalkyl moiety <2002S365>. The synthesis of benzyl chloroformate from benzyl alcohol and phosgene was studied. The application of benzyl chloroformate in polypeptide synthesis has been introduced <2001MI35>.

(iii) Chlorination of carbonate Trichloromethyl chloroformate is prepared from methyl formate or methyl chlorocarbonate in reactor under stirring using an ultraviolet (UV) high-pressure mercury lamp <1998PRP1172102> (Equation (18)). +

CH3OCOOCH3

Cl2

Cl3COCOCl

ð18Þ

(iv) Preparation of -halogenated chloroformates from aldehyde and phosgene -Chlorinated chloroformates, useful as pharmaceutical intermediates, are prepared by the reaction of phosgene with an aldehyde in the presence of a catalyst comprising alkyl-substituted guanidines, hexa-substituted guanidinium chlorides, or bromides. Thus, acetaldehyde reacted with phosgene in the presence of pentabutylguanidine, producing 1-chloroethyl chloroformate in 88.9% yield <1998USP5712407> (Equation (19)). Similarly, benzaldehyde-derived chloroformates have also been made and used in the synthesis of novel insecticides <2001TL7751>. H + O

COCl2

O

Cl

ð19Þ O

Cl

(v) Preparation of -halogenated chloroformates by halogenation of chloroformates An improved process for concurrently preparing 1-chloroethyl chloroformate and 2-chloroethyl chloroformate with improved selectivity, was achieved by chlorination of ethyl chloroformate, optionally in presence of a free radical initiator. Ethyl chloroformate was chlorinated with chlorine gas in the presence of a free radical initiator 2,2-azobis(2-methylpropanenitrile) to give a mixture of 1-chloroethyl- and 2-chloroethyl-chloroformate <1994USP5298646>. Preparation of trichloromethyl chloroformate has been achieved by a photochemical chlorination process of methyl chloroformates. For example, this process comprises adding PCl5 to methyl chloroformate and heating to 30–50 C under light, treating with chlorine for 70–80 h while absorbing HCl with lime water <1998PRP1192434> (Equation (20)). CH3OCOCl

+

PCl5

Cl3COCOCl

ð20Þ

Preparation of chloromethyl chloroformate was done by free radical chlorination, using sulfuryl chloride and 2,20 -azobisiobutyronitrile (AIBN), of methyl chloroformate. The product, chloromethyl chloroformate, thus obtained was reacted with alcohols to give alkoxycarbonyloxymethyl

418

Functions Containing a Carbonyl Group and at Least One Halogen

chlorides as intermediates for pharmaceuticals <1996JAP08040986> (Equation (21)). Chloromethyl chloroformate has also been used in the synthesis of trichloroacryloyl chloride <1993MI001>. CH3OCOCl

+

SO2Cl2

ð21Þ

ClCH2OCOCl

(vi) Nonphosgene methods Chloroformate esters are prepared by treating 1 mol of HCl or nitrosyl chloride with 0.1–100 mol of nitrite esters and CO in the presence of Pt-group metal catalysts. A mixture of HCl, CO, MeONO, NO, and MeOH (0.6:6:7:2:8) was passed through PdCl2/alumina at 60 C to give 100% ClCO2Me <1994JAP06306017> (Equation (22)).

HCl

+ CO

+

MeONO +

NO +

MeOH

PdCl2/Al2O3

MeOCOCl

ð22Þ

Chloroformate esters are also prepared by treating 1 mol of chlorine with 0.1–100 mol of nitrite esters and CO in the presence of supported Pt-group metal catalysts. A mixture of chlorine, CO, MeONO, NO, and MeOH (1:7:6:2:6) was passed through PdCl2/alumina at 120 C to give 18% ClCO2Me (based on chlorine) <1994JAP06306016>. Similar preparations are reported for the synthesis of alkyl chloroformate where the methyl nitrite has been replaced with alkyl nitrite ester <1994BCJ2554>. Methyl chloroformate has been synthesized via direct interaction of palladium bis(methoxycarbonyl) complexes with CuCl2 <1993JOM243> (Equation (23)). ClCOOMe has been obtained in 80% yield by reaction of [PdL2(COOMe)2] [L2 = 2,20 -bipyridine (bipy) or 1,10-phenanthroline (phen)] with CuCl2. [Pd (bipy) (COOMe)2]

+

4CuCl2

THF

ð23Þ

MeOCOCl

Benzyl chloroformate synthesis using carbon monoxide as a carbonyl source has been reported <2002T10011>. A novel nonphosgene synthetic method for benzyl chloroformate has been established. SMe O–benzyl carbonothioates were prepared by the carbonylation of benzyl alcohols with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) followed by esterification using methyl iodide in good yields. Then, the benzyl chloroformates were successfully synthesized by the chlorination of SMe O–benzyl carbonothioates using sulfuryl chloride in excellent yields (Equation (24)). CH2OH +

CO

S/DBU

CH2OCOSMe

SCl2

CH2OCOCl

ð24Þ

A novel synthetic method for benzyl chloroformate using carbon monoxide or carbonyl sulfide as a carbonyl source has been established. Benzyl chloroformate was successfully synthesized by the chlorination using sulfuryl chloride of PhCH2O2CSMe, which was prepared by the carbonylation of benzyl alcohol with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of DBU (1,5-diazabicyclo[5.4.0]undec-5-ene) followed by esterification using methyl iodide <2002TL7765>.

(vii) Other chloroformates An oxime of an estradiene derivative was reacted with phosgene or diphosgene to give a chloroformate derivative <2002GEP10056677> (Equation (25)).

419

Functions Containing a Carbonyl Group and at Least One Halogen HO

O

Cl

N

N

O OR

H Me

OR

H CH2OR

Me

COCl2

CH2OR

ð25Þ

H

H O

O

Methyl 11C-labeled methyl chloroformate, a novel 11C-acylating agent, was formed by the reaction of 11C-labeled methanol and phosgene <1995MI365>.

6.14.4.1.3

Bromoformate esters

From COFGT (1995) <1995COFGT(6)407> it is known that these compounds, bromoformate ester, are prepared by two approaches. One using the reaction of alcohols with carbonyl dibromide, and two using the bromide exchange reaction on the chloroformates. Up until the end of 2003, no new approaches have been reported for making bromoformate esters.

6.14.4.1.4

Iodoformate esters

Stable iodoformates were reported in COFGT (1995) <1995COFGT(6)407>. The first iodoformate, 9-triptycyl iodoformate, was made photochemically from its 9-triptycyl monoester of oxalic acid. Iodoformates have also been synthesized by using the iodide exchange reaction on chloroformates. Up until the end of 2003, there have not been any new approaches to the synthesis of iodoformates.

6.14.4.2

One Halogen and One Sulfur

Similar to the oxygen system of haloformate esters, here again in the halothiolformate esters the synthetic methods mentioned in COFGT (1995) <1995COFGT(6)407> are summarized in Scheme 5. The insertion of carbon monoxide to sulfenyl halide, the nucleophilic displacement of one of the halogen in carbonyl dihalide with a thiol, and the halogen exchange on a halothiolformate are the three general routes to halothiolformate esters. COX2

RSH –HX

RSCOX

RSCl

CO

X1–

RSCOX1 + X–

Scheme 5

Structures and conformations of (fluorocarbonyl)trifluoromethylsulfane and that of (chlorocarbonyl)trifluoromethylsulfane have been determined by gas electron diffraction, vibrational spectroscopy, and theoretical calculations <1997JPC2173>.

6.14.4.2.1

Fluorothiolformate esters

The preparation of fluorocarbonyl sulfenyl bromide from fluorocarbonyl sulfenyl chloride and trimethylsilyl bromide was described in COFGT (1995) <1995COFGT(6)407>. A photochemical

420

Functions Containing a Carbonyl Group and at Least One Halogen

study has been done with this compound. Under photochemical conditions, this fluorothiolformate ester eliminates carbon monoxide to give sulfur bromide fluoride <1993IC948>.

6.14.4.2.2

Chlorothiolformate esters

Here one should be careful not to confuse the thiono formates, with sulfur in the thiocarbonyl group (C¼S), with that of thiol formates, with sulfur in the thiol group (CS). In some cases the thiono formates could rearrange to thiol formates as seen with the allylic thiono chloroformates.

(i) From phosgene and thiols Thiochloroformates are manufactured with reduced amount of by-products by reacting thiols with phosgene in the presence of ureas as a catalyst. For example, phosgene and n-octanethiol with N,N-dimethylpropyleneurea as the catalyst, gave mainly n-octylthio chloroformate with very small amounts of thiocarbonate and disulfide as impurities <1999GEP19737619>.

(ii) By rearrangement of allylic thionochloroformates Treatment of allylic alcohols with thiophosgene and pyridine gives thiolo chloroformates directly at rt, presumably via a very rapid [3,3]-sigmatropic rearrangements of thionochloroformates. Synthesis of allyl thionochloroformate from allyl alcohols sodium hydride and thiophosgene at low temperature and warming up to rt supports this finding <1999TL8059>. Thiophosgene, as seen above, has been used in the synthesis of thiochloroformates. General reviews on the industrial synthesis of thiophosgene and derivatives are available <1998MI252, 1997OPRD240>.

6.14.4.2.3

Bromothiolformate esters

These compounds, bromothiolformate esters, have rarely been reported <1995COFGT(6)407>. Bromide exchange on a fluorothiolformate has been reported to make trifluoromethyl bromothiolformate and carbon monoxide insertion on methylsulfenyl bromide has been used to make methyl bromothiolformate. Up until the end of 2003, new methods for the synthesis of bromothiolformate esters were not found in the literature.

6.14.4.2.4

Iodothiolformate esters

Similarly to what was reported in COFGT (1995) <1995COFGT(6)407>, the present authors did not find any reference to this class of compounds in the period up to 2003.

6.14.4.3

One Halogen and One Nitrogen

The general methods reported in COFGT (1995) <1995COFGT(6)407> for the preparation of the above-mentioned compounds are summarized in Scheme 6. The reaction of carbonyl dihalide with primary, secondary, and tertiary amines leads to carbamoyl halides, which in the case of a primary amine could further be converted into isocyanates, an important industrial compound. The secondary amine carbamoyl halides could also be synthesized from either carbon monoxide insertion into dialkyl haloamines, or halogenation of N,N-dialkyl formamides. Halo cyanato and halo thiocyanato carbonyl compounds are made by nucleophilic displacement of the corresponding anions source with a carbonyl dihalide.

421

Functions Containing a Carbonyl Group and at Least One Halogen SCNCOCl SCN– R1R2R3N

R1R2R3N+COCl Cl

RNH2

COCl2

HCl

RNHCOCl

RNCO

–

NCO–

R1R2NH R1R2NCl

OCNCOCl

R1R2NCOCl

CO

Cl2 R1R2NCOH

Scheme 6

6.14.4.3.1

Carbamoyl fluorides

Carbamoyl fluorides formed by the addition of hydrogen fluoride on to an isocyanate are used as fluorinating agents, specifically for converting a chloride into a fluoride. For example, para(trifluoromethyl)phenyl isocyanate is prepared from para-(trichloromethyl)phenyl isocyanate and hydrogen fluoride in the presence of tin tetrachloride. A carbamoyl fluoride is suggested as the intermediate in this reaction, which is isolated in small amounts from the reaction mixture <2002WOP0255487> (Scheme 7).

O C

O C

O HN

N +

HF

F

HN

N

SnCl4

CCl3

O F

+

CCl3

CF3 97%

CF3 3%

Scheme 7

Experimental and theoretical investigations of the geometry and conformation of fluorocarbonyl isocyanate and fluorocarbonyl azide were carried out. These were compared with that of their corresponding precursors, formyl isocyanate and formyl azide, respectively. The present authors warn that fluorocarbonyl azide is an explosive and should be handled only with proper safety precautions and in millimolar quantities <1993JST197>. N-fluoroformyliminotrifluoromethylsulfur fluoride, FCON¼S(F)CF3, has been studied using vibration spectroscopy and theoretical calculations <2000MI881>.

6.14.4.3.2

Carbamoyl chlorides

Carbamoyl chlorides have also been made using the phosgene substitute, trichloromethyl carbonate or triphosgene. The effects of solvent, reaction time and temperature, feed ratio, and dosage of nucleophile on the yield have been discussed <2000MI16>. Solid-phase synthesis of ureas of secondary amines via carbamoyl chloride has been reported. Secondary amines attached to a solid support such as the Wang resin can be converted to the corresponding carbamoyl chlorides by treatment with phosgene or triphosgene <1997TL1895>.

422

Functions Containing a Carbonyl Group and at Least One Halogen

A novel synthesis of 3-substituted 1-chlorocarbonylimidazolidin-2-ones using triphosgene or bis(trichloromethyl)carbonate has been reported. The yields and purity of the products obtained are better than those obtained by a conventional method using phosgene <2000JCR(S)440, 2000OPP498>. New and efficient palladium-catalyzed routes to carbamoyl chlorides have been reported. The palladium-based catalytic system is very active and operates in two steps, avoiding the synthesis of phosgene, but making use of carbon monoxide and chlorine as in phosgene chemistry. Primary amines lead directly to isocyanates and the secondary amines lead to carbamoyl chlorides <2000OM3879>.

6.14.4.3.3

Carbamoyl bromides

Carbamoyl bromides or N-bromocarbonyl compounds have been made as reported in COFGT (1995) <1995COFGT(6)407> using the general methods used for the preparations of carbamoyl halides. The addition of hydrogen bromide to an isocyanate or the exchange of chloride in carbamoyl chlorides with a bromide source are the two common approaches to the synthesis of carbamoyl bromides. Up until the end of 2003, new methods for the synthesis of carbamoyl bromides have not been seen in the literature.

6.14.4.3.4

Carbamoyl iodides

These compounds are suggested to be not very stable according to COFGT (1995) <1995COFGT(6)407>. Only one approach, that of addition of hydrogen iodide to an isocyanate, has been reported for the synthesis of carbamoyl iodides. There have been no new reports on the synthesis of this class of compounds, up to the end of 2003.

6.14.4.4

One Halogen and One Phosphorus

Synthesis of compounds belonging to this section, mentioned in COFGT (1995) <1995COFGT(6)407>, is summarized in Scheme 8. The trivalent phosphorus compounds could further react either by elimination of CO to give phosphorus halide, or by elimination of hydrogen halide to give phosphaketene. The reaction of trisalkoxy phosphorus with carbonyl dihalide gives alkyl halide and (dialkoxyphosphinyl)formyl halide, a pentavalent phosphorus compound (Arbuzov reaction).

R1R2PSiMe3

COCl2

R1R2PCOCl

R1R2PCl

R2 = H

R1P=C=O (RO)2POCOCl + RCl

(RO)3P + COCl2

Scheme 8

6.14.4.4.1

Chlorocarbonyl derivatives of phosphorus(III)

The reaction of triphenylmethyl-substituted primary and secondary phosphines with phosgene has been studied. The nature of the product with the trityl-substituted primary phosphine depends on the nature of the solvent. In toluene, the initially formed chlorocarbonyl phosphorus compound is stable, but it loses CO in methylene chloride to give a chlorophosphine, and loses HCl in ether

Functions Containing a Carbonyl Group and at Least One Halogen

423

solvent to give a phosphaketene, which dimerizes. In the case of the trityl-substituted secondary phosphine, the nature of the product depends on the nature of the second substituent on phosphorus. When the substituent was phenyl, the initial adduct, chlorocarbonyl phosphorus compound, was very stable, and when the substituent was a t-butyl the initial adduct readily lost the CO to give the corresponding chlorophosphine compound <1999ZAAC1979>. In the same paper the reaction of diphosphine with phosgene was reported. It was found to be inert in the absence of hydrogen chloride. In the presence of HCl the PP bond was cleaved to give the primary phosphine and the chlorophosphine as the products <1999ZAAC1979>. All these reactions are summarized in Scheme 9. COCl2/ether

COCl2/CH2Cl2

Ph3CPHCOCl

Ph3CPH2

Ph3CPHCOCl –CO

COCl2/ toluene

Ph3PHCl

–HCl

(Ph3CPCO)2

Ph3CPHCOCl

Ph3CPCl2 + Ph3CPRCl

(Ph3CPH)2

COCl2 R

= But

COCl2

Ph3CPRH

COCl2 HCl

Ph3CPRCOCl

R = Ph

Ph3CPH2 + Ph3CPHCl

Scheme 9

Another way these chlorocarbonyl phosphorus compounds have been made is via anhydrous HCl hydrolysis of phospha–urea compound, where the cleavage of a PCO bond occurs leading to a phosphine and a chlorocarbonyl phosphorus compound. This reaction is depicted in Scheme 10 <1999ZAAC919>.

HCl (Ph3CPH)2CO

Ph3CPH2

+

Ph3CPHCOCl

Scheme 10

6.14.4.4.2

Chlorocarbonyl derivatives of phosphorus(V)

A facile one-pot preparation of phosphonothiolformates, useful reagents for the synthesis of carbamoylphosphonates, was accomplished by sequential reaction of phosgene solution with alkane thiols, to form the chlorothiolformates, followed by Arbuzov reaction with trialkylphosphites <2000SL815>.

6.14.4.5

One Halogen and One Arsenic, Antimony, or Bismuth

As in COFGT (1995) <1995COFGT(6)407> any reports on these compounds were not seen.

6.14.4.6

One Halogen and One Metalloid (Boron, Silicon, or Germanium)

Preparation of this class of compounds has not been reported, in the period up to 2003, as was similarly observed in COFGT (1995) <1995COFGT(6)407>.

424 6.14.4.7

Functions Containing a Carbonyl Group and at Least One Halogen One Halogen and One Metal

The organometal carbonyls reactions with halogens are known to give organometal carbonyl halides <1995COFGT(6)407>. These compounds could further lose carbon monoxide to give organometal halides. The synthesis of metal bromides and their bromide oxides by the use of carbonyl dibromide must have gone through bromocarbonyl metal intermediates. Carbonyl dibromide reacted with a wide selection of d- and f-block transition-metal oxides to form either the metal bromide or bromide oxide. The reaction was done, by heating the metal oxides at 125 C for 10 days with excess carbonyl dibromide in a sealed tube. Under these conditions V2O5, MoO2, Re2O7, Sm2O3, and UO3 were converted into VOBr2, MoO2Br2, ReOBr4, SmBr3, and UOBr3, respectively <1997JCS(D)257>. No new synthetic method for this class of compounds has been seen in the period 1993–2003. All the references were to complexes with halogens and carbonyls attached directly to the metals, which are beyond the scope of this chapter.

6.14.4.7.1

Halocarbonyl complexes of first transition metal series (iron and chromium)

No new synthetic methods for this class of compounds have been reported in the period 1993–2003, other than those mentioned in COFGT (1995) <1995COFGT(6)407>.

6.14.4.7.2

Halocarbonyl complexes of second transition metal series (ruthenium and rhodium)

No new synthetic methods for this class of compounds have been reported in the period 1993–2002, other than those reported in COFGT (1995) <1995COFGT(6)407>.

6.14.4.7.3

Halocarbonyl complexes of third transition metal series (rhenium and iridium)

No new synthetic method for this class of compounds have been reported, other than those mentioned in COFGT (1995) <1995COFGT(6)407>, briefly discussed above.

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427

Biographical sketch

Ramiah Murugan was born in Madurai, India. He obtained B.Sc. in chemistry in 1975 from American College, Madurai, Tamil Nadu, India and an M.Sc. in chemistry in 1977 from Madurai University. After four years of Junior Scientist work at Madurai University, he joined Professor A. R. Katritzky’s group at the University of Florida, USA and obtained his Ph.D. in 1987. He stayed there for two more years doing postdoctoral work in the area of high-temperature aqueous organic chemistry. He joined Reilly Industries in 1989 and is currently a Senior Research Associate. His research interests include synthesis of intermediates for pharmaceuticals, agrochemical products, and performance products; mechanistic studies; catalysis; polymer chemistry; and process development.

Subbarao Yarlagadda received his M.Sc. in organic chemistry from Andhra University, Waltair, India. He obtained his Ph.D. in 1991 from the Indian Institute of Chemical Technology (IICT), Hyderabad, India. His doctoral work was chiefly on selective organic transformations by using a new class of heterogenized homogeneous catalysts. Later, he joined as a postdoctoral fellow with Professor M. Graziani at the University of Trieste, Italy under the UNIDO program, and worked on polydentate ligands and their metal complexes for an oxidative amination reaction. From 1992 to 1996, he was a staff scientist in Dr. A.V. Ramarao’s group at IICT, India, and worked on the synthesis of fine and specialty chemicals, pharmaceutical intermediates by using zeolite catalysts. In 1996, he joined Professor P. A. Jacobs at the Katholieke University of Leuven, Belgium and worked on Mesoporous zeolites and homogeneous catalysts for the synthesis of specialty chemicals. Since July 1998, he has been with Reilly Industries, Indianapolis, IN, USA as a Research Associate. His current interests include the process development, invention of new routes for the existing products, synthesis of fine and specialty chemicals, development of new catalysts for the synthesis of pharmaceutical and agrochemical intermediates, and vitamins.

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 409–427

6.15 Functions Containing a Carbonyl Group and at Least One Chalcogen (but No Halogen) H. ECKERT Technical University Munich, Garching, Germany 6.15.1 CARBONYL CHALCOGENIDES WITH TWO SIMILAR CHALCOGEN FUNCTIONS 6.15.1.1 Two Oxygen Functions 6.15.1.1.1 Carbonates from phosgene and substitutes, chloroformates 6.15.1.1.2 Carbonates from carbon oxides and carbonate salts 6.15.1.1.3 Carbonates from ureas 6.15.1.1.4 Cyclic carbonates and transesterification 6.15.1.1.5 Acylcarbonates 6.15.1.1.6 Carbonates by iodolactonization 6.15.1.1.7 Polycarbonates 6.15.1.2 Two Sulfur Functions 6.15.1.2.1 Dithiocarbonates by [3,3]-sigmatropic rearrangement 6.15.1.2.2 1,3-Dithiol-2-ones by xanthogen disulfide-alkyne cycloaddition 6.15.1.2.3 Mixed methods 6.15.1.3 Two Selenium Functions 6.15.2 CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDE ATOM FUNCTIONS 6.15.2.1 Oxygen and Sulfur Functions 6.15.2.1.1 Thiocarbonates from activated carbonates 6.15.2.1.2 Thiocarbonates from alkoxycarbonylsulfenyl chlorides 6.15.2.1.3 Thiocarbonates from carbonothioic acid salts 6.15.2.1.4 Other methods 6.15.2.2 Other Dissimilar Chalcogenide Functions 6.15.2.2.1 Oxygen and selenium functions 6.15.2.2.2 Oxygen and tellurium functions 6.15.2.2.3 Sulfur and selenium functions 6.15.3 CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTION AND ONE OTHER HETEROATOM FUNCTION 6.15.3.1 Oxygen and Nitrogen Functions 6.15.3.1.1 Carbamates from chloroformates or phosgene equivalents 6.15.3.1.2 Carbamates from isocyanates 6.15.3.1.3 Carbamates from N,N0 -carbonyldiimidazole (CDI) 6.15.3.1.4 Carbamates from carbonates or dicarbonates 6.15.3.1.5 Carbamates from carbon oxides 6.15.3.1.6 Carbazates 6.15.3.1.7 Azidoformates 6.15.3.2 Oxygen and Phosphorus Functions 6.15.3.2.1 Phosphinecarboxylates by the Arbuzov reaction and related methods 6.15.3.3 Oxygen and Other Heteroatom Functions 6.15.3.3.1 Oxygen and boron functions

429

430 430 430 432 433 433 434 434 435 435 435 435 436 436 436 436 436 437 437 438 438 438 439 440 440 440 440 441 441 442 443 444 444 444 444 445 445

430

Functions Containing a Carbonyl Group and at Least One Chalcogen

6.15.3.4 Sulfur and Nitrogen Functions 6.15.3.4.1 Thiocarbamates from chlorothioformates and amines 6.15.3.4.2 Thiocarbamates from carbamoyl chlorides and thiols 6.15.3.4.3 Thiocarbamates from isothiocyanates and alcohols 6.15.3.4.4 Thiocarbamates from alkylamide salts, carbon monoxide, and sulfur 6.15.3.4.5 Thiocarbamates from [3,3]-sigmatropic rearrangement 6.15.3.4.6 Thiocarbamates from trichloroacetyl chloride, thiols, and amines 6.15.3.5 Sulfur and Phosphorus Functions 6.15.3.5.1 Phosphonothioformates 6.15.3.6 Other Mixed Systems 6.15.3.6.1 Selenium and nitrogen functions 6.15.3.6.2 Tellurium and nitrogen functions

6.15.1

445 445 445 446 446 446 447 447 447 447 447 449

CARBONYL CHALCOGENIDES WITH TWO SIMILAR CHALCOGEN FUNCTIONS

An overview on all functional group transformations, which can be accomplished by use of phosgene as well as by use of about 70 phosgene substitutes and equivalents, has been presented in 2003 by Cotarca and Eckert in Phosgenations—A Handbook .

6.15.1.1

Two Oxygen Functions

Carbonic acid is principally a difunctional carboxylic acid; therefore, manifold preparative accesses for a great variety of its organic derivatives exist, which differ widely in rate and selectivity of reactions and reagents. Some reviews have been published .

6.15.1.1.1

Carbonates from phosgene and substitutes, chloroformates

Phosgene, as the formal carboxylic acid dichloride of carbonic acid, is a highly reactive reagent, which affords high turnovers and good yields. Thus, both symmetrical and unsymmetrical dicarbonates, the latter via chloroformates, can easily be produced. A key intermediate of the decalin part of azadirachtin, an antifeedant, insect growth regulatory, and reproductive effective substance from the Neem tree Azadirachta indica, has been prepared by carbonylation of the alcohol with methyl chloroformate, affording the carbonate (Equation (1)) <2000S1878>. O

TBDMS O

O

O

TBDMS O

O

Cl-CO2Me

OH O

O

ð1Þ

Pyridine, DCM 0 °C, 70 min, then, rt, 40 min 70%

O O

OMe

O O

During a nice enantioselective total synthesis of epothilone A using multifunctional asymmetric catalysis (Suzuki cross-coupling of fragment A with fragment C, followed by Yamaguchi lactonization), the reaction of the aldehyde with TMS-acetylide affords an alcohol, which is methoxycarbonylated with methyl chloroformate resulting the carbonate (Equation (2)) <2000JA10521>. _

Li + THF, –78 °C 40 min

i. TMSS N CHO OTBS

O

S N

O

ð2Þ

O

ii. MeOCOCl 30 min, 79%

OTBS

TMS

431

Functions Containing a Carbonyl Group and at Least One Chalcogen

A carbonate intermediate for the synthesis of functionalized ‘‘pyridoindoles,’’ which have attracted great interest by virtue of their cytotoxic activity toward leukemia cells, has been prepared by using ethyl chloroformate <2001T4787>. Phenyl chloroformate has been employed in the cyclocarbonylation reaction to prepare an intermediate in synthesis of solanoeclepin A <2000CC1463>. Functionalization of taxol, which is a powerful anticancer drug, in the position 2, is an important pharmaceutical tool. This can be achieved advantageously by cyclocarbonylation of the 1,2-diol at 13-deoxy-7-TES baccatin III with phosgene yielding 95% of the corresponding 1,2-cyclocarbonate (Equation (3)), which will further be reacted with alkyllithium compounds to afford 2-acylbaccatin derivatives under ring opening of the 1,2-cyclocarbonate <1994CC295>. AcO

O

AcO

OTES

O

OTES

COCl2 1

2

H

HO

OH

Pyridine 25 °C, 30 min 95%

O OAc

1

2

H

O

O

ð3Þ

O OAc

O

A highly interesting synthetic route for preparing intermediates of ‘‘retinal’’ comprises a palladium-catalyzed transformation of an ‘‘yne-carbonate’’ into an ‘‘allenyl enal.’’ The carbonate is prepared by unsymmetrical carbonylation of propargylic alcohol and silyl enol ether with phosgene, each step with 90% yield (Scheme 1) <1994TL7383>. Ph

Ph

Cat. Pd(PPh3)4

i. BuLi O

OH ii. COCl2

Ph

O

CHO

–CO2

O

90%

iii. TMSO MeLi 90%

Scheme 1

In all reactions previously described phosgene is the basic chemical for the preparation of carbonates in a direct way as well in the synthesis of the chloroformates. Phosgene itself is a poisonous gas which was discovered in 1812 by Davy from the action of sunlight on carbon monoxide and chlorine. Extensive safety precautions are required to prevent exposure to phosgene during handling. In order to avoid the difficulties associated with the toxicity of phosgene gas, equivalents and substitutes for phosgene as well as the ‘‘safety phosgenation’’ have been developed . Another often used phosgene equivalent to accomplish carbonylation reactions is the solid 1,10 -carbonyldiimidazole (CDI). The conversion of (RS)-sec-phenethyl alcohol to its 2,2,2-trifluoroethylcarbonate, which is needed for the resolution of ‘‘chiral alcohols,’’ by using CDI in good yield has been described (Scheme 2) <2000TA1279>. O

O O

OH

N N

O

N

CDI

N

N

O

N CF3

OH

10% DMAP DCM, rt, 24 h 85%

DCM, rt, 2 h 98%

Scheme 2

O

CF3

432 6.15.1.1.2

Functions Containing a Carbonyl Group and at Least One Chalcogen Carbonates from carbon oxides and carbonate salts

The bulk chemical diphenyl carbonate (DPhC), which is an important reagent in the manufacture of polycarbonates, has been produced by the oxidative carbonylation of phenol with carbon monoxide (CO) and air-oxygen catalyzed by Pd dinuclear complexes and redox catalyst (Equation (4)) <1999JMOC(148)289, 2000JMOC(154)243>. Reaction proceeds smoothly on a Pd dinuclear complex bridged with a pyridylphosphine ligand [Pd2(Ph2Ppy)2X2] and redox catalyst along with ammonium halide in the presence of CO and air at 100 C and the TOF reaches 19.21 (mol-DPhC/mol-Pd h). OH CO, O2

O H2O

+

2 Pd2(Ph3PPy)2Cl2 Redox catalyst

ð4Þ

O

O

DPhC

NH4Cl, 100 °C

Dialkylcarbonates have been prepared from CO2 and alkanols under Appel conditions by using tri-(1-butyl)-phosphane, tetrabromomethane, and cyclohexyl tetramethylguanidine (CyTMG). This strong, hindered, and non-nucleophilic base is more effective than other bases such as DBU. DMF is the solvent of choice (Equation (5)) <1996CL825>. Yields of dialkyl carbonates derived from various primary alkanols are 54–91%; from secondary alkanols they are 14–22%. + 2ROH

+

n-Bu3P

CyTMG

CBr4

DMF 54–91%

CO2 +

+

O OR

n-Bu3P=O

ð5Þ

OR +

CHBr 3

A three-component coupling system of aliphatic alcohol/CO2/alkyl halide under a pressure of 160 psig CO2 and in the presence of a peralkylated guanidine has been applied to prepare dialkylcarbonates <1995JOC6205>. Thus, di-1-butylcarbonate is obtained in 73% yield (by GC). An approach to synthesize ‘‘mixed’’ dialkylcarbonates employs the above three-component coupling system aliphatic alcohols/CO2/alkyl halides in the presence of Cs2CO3 and without pressure of CO2 (Scheme 3). This method shows a great variety in use of alcohols and alkyl halides (Table 1), reaction times are 2.5–23 h, yields of the resulting mixed dialkylcarbonates are 91–98% <1999JOC4578>.

Ph

OH

Ph

OBu

O O

Cs2CO3 TBAI

DMF 23 °C, 3.5 h

_

Ph

O

Cs +

1-BuBr CO2

92% _

Ph

O

O

Cs +

O

Scheme 3

One of the most attractive synthetic goals starting from CO2 is the bulk chemical dimethylcarbonate (DMC). An approach is the organostannane-catalyzed reaction of dehydrated derivatives of methanol (ortho-ester and acetals) with ‘‘supercritical’’ CO2 <1999JA3793, 1998JOC7095, 2000POL573>. The reaction of acetals is especially attractive because the starting material is much less expensive compared with ortho-esters, and the co-produced acetone can be recycled (Scheme 4).

Functions Containing a Carbonyl Group and at Least One Chalcogen

433

Dialkyl carbonate formation using alcohols, halides, and CO2 in the presence of Cs2CO3

Table 1

Alcohol (ROH)

Halide (R0 -X)

4-Phenylbutanol

t-Butyl 2-bromoacetate Benzyl chloride Allyl bromide s-Butyl bromide n-Butyl bromide t-Butyl 2-bromoacetate Benzyl chloride n-Butyl bromide MPMCl

2-Phenylpropanol

Time (h)

Yield (%)

5 2.5 4 23 4.5 5 3 5 3

95 94 91 98 92 96 98 96 92

Source: <1999JOC4578>.

O

O

Supercritical CO2 MeO cat. Me2Sn(OMe)2

O

O + OMe

+2 MeOH –H2O

Scheme 4

6.15.1.1.3

Carbonates from ureas

Processes to produce DMC in high yield are of great interest. There is a need for low-cost DMC, because it becomes more and more important in fuel application as a gasoline additive. DMC has many desirable properties: almost 3 times the oxygen content of methyl t-butyl ether (MTBE), good octane for blending (RON of 130), lower volatility than MTBE, and biodegradability. Reaction of methanol with urea to give DMC is a well-known low-yield synthesis, but the use of triethylene glycol dimethyl ether (triglyme) as a solvent, in conjunction with tin catalysts, affords high yields of DMC to be realized (Scheme 5) <1999USP5902894, 1998JAP10259165>. More details on this process are also described in . O

O H2N

NH2 + 2MeOH

NH2

H2N

2NH3 + CO2 Diglyme tin-cat. 180 °C

+ H2O

O OMe + 2NH3

MeO

O 2MeOH +

CO2

98% MeO

OMe

+ H2O

DMC

Scheme 5

6.15.1.1.4

Cyclic carbonates and transesterification

Transesterification is used industrially to produce DMC and diethylcarbonate as shown in recent patents. Dowex MSA 1, CoYO, and Y2O3 are used as catalysts (Equation (6)) <1992JAP04198141, 1997JAP09040616, 2001JAP2001316332>.

434

Functions Containing a Carbonyl Group and at Least One Chalcogen O

O

Cat. O

O

+ 2MeOH

OMe

MeO

+

OH

HO

ð6Þ

DMC

The above-presented process with CoYO as catalyst is also employed in the production of diphenyl carbonate (DPhC) in 95% yield from ethylene carbonate (EC) (Equation (7)) <1997JAP09040616>. It is a continuous process using a fixed bed reactor at 130 C, a pressure of 9 kg cm2, and an LHSV of 3 h1. O O

i. MeOH ii. PhOH O

O

Cat., 130 °C 95%

O

+

OH

HO

ð7Þ

O

DPhC

(i) Enzyme catalysis In a transesterification process by selective alkoxycarbonylation using enzymes in organic solvents as catalysts, the A-Ring precursor of vitamin D3 has been prepared. Candida antarctica lipase (CAL) is found to be the best catalyst in toluene (Equation (8)). Other enzymes are PSL and CVL, other solvents are THF and 1,4-dioxane, yields of alkoxycarbonylation products depend strongly on conditions and are 17–100%. Regioselective alkoxycarbonylation occurs only at the C-5-(R) hydroxy group <1997JOC4358, 2001JOC4227>.

Enzyme Cal Toluene

O + HO

O

O

N

30 °C, 4 h 100%

OH

ð8Þ

O O

O

OH

Enzymatic acylation in organic solvents has also been employed to synthesize water-soluble Paclitaxel derivatives. Thus, potential new ‘‘prodrugs’’ can be generated possessing high solubility in water. The approach involves an enzymatic acylation of ‘‘paclitaxel’’ with a bifunctional acylating reagent, catalyzed by enzyme ‘‘thermolysin’’ (from ‘‘bacillus thermoproteolyticus rokko’’) to give an activated carbonate dervative (conversion 83%) <1997JA11554>.

6.15.1.1.5

Acylcarbonates

A detailed review on di-t-butyldicarbonate (BOC2O), a widely used standard reagent for the introduction of the BOC-group, in its reactions with alcohols in the presence of DMAP is given by Hassner and Basel <2000JOC6368>. Many general procedures for reactions of BOC2O with common alcohols affording O-BOC-derivatives and/or symmetrical carbonates are described (Equation (9)). O

O ROH +

But O

O

O But

BOC2O

6.15.1.1.6

MeCN

O

O

DMAP RO

OBut

+ RO

OR

ð9Þ

Carbonates

Carbonates by iodolactonization

An intermediate carbonate 1 for an iodolactonization reaction has been accomplished by using the acylcarbonate BOC2O in excellent yield of 98% <1999JOC3798>.

Functions Containing a Carbonyl Group and at Least One Chalcogen

435

O-But H

O

O C6H11 1

6.15.1.1.7

Polycarbonates

For polycarbonates there is a huge and fast-growing market. They are excellent engineering thermoplastics and substitutes for metals and glass because of their good impact strength, heat resistance, and transparency, which makes it an ideal material for optical data-storage devices. A number of synthetic routes for producing polycarbonates have been described. During this process phenol is removed by distillation and recycled by transesterification with DMC to afford DPhC which is employed again in the polycarbonate production process <1994CBR970, 1996PAC367, B-2003MI615-05>.

6.15.1.2 6.15.1.2.1

Two Sulfur Functions Dithiocarbonates by [3,3]-sigmatropic rearrangement

Alkylxanthate undergoes a thermal [3,3]-sigmatropic rearrangement to form the dithiocarbonate, which is the starting material for a novel rearrangement of allylic thionitrites to thioepoxides (Equation (10)) <2002CC2394>. R1

S R3

6.15.1.2.2

S

ð10Þ

SMe

Reflux, 7 h

R2

R1

R3

THF

SMe

O

R2 O

1,3-Dithiol-2-ones by xanthogen disulfide-alkyne cycloaddition

1,3-Dithiol-2-ones (cyclic dithiocarbonates) have been prepared in a single-step synthesis from diisopropylxanthogen disulfide and an alkyne in a radical cycloaddition reaction <1995CC1429, 1998H2003, 2003OBC129>. The method is versatile and provides good yields; in particular, with arene-substituted alkynes, starting materials are commercially available. The radical cyclization is initiated by AIBN <1995CC1429> (Scheme 6). The scope of the reaction can be extended to some alkenes such as bornene and norbornene <1998H2003>. S S

O

S

AIBN

O

S

2

Heat

O

S

.

S R

.

O S +

R

. S

R

R=

*

*

O

S

76–82% S

MeO

* CO2Me

Scheme 6

* HO

*

436

Functions Containing a Carbonyl Group and at Least One Chalcogen

This proven method has been applied to the preparation of an intermediate of molybdopterin, where the needed alkynes are disubstituted, yields are similar to those reactions with monosubstituted alkynes (Equation (11)) <2003OBC129>. For work-up only flash chromatography is necessary. O O O

S

H

N

AIBN Toluene

N

S

H

N

2 x 1.5 h Reflux 77%

+ S O

S

ð11Þ

O

N

O

O

S S

6.15.1.2.3

Mixed methods

Besides these classical methods some less common synthetic approaches have been published. Benzo-1,3-dithiol-2-ones are important precursors for tetrathiofulvalenes (TTFs) which have been successfully used as building blocks for low-dimensional organic conductors and superconductors. They have been prepared from benzo-1,3-dithiol-2-thiones (Equation (12)) <2003AG(E)2765>. By the same method a 1,3-dithiol-2-one intermediate has been prepared for the synthesis of a zinc(II) phthalocyanine derivative functionalized with four peripheral substituted TTF units <2002JHC1071>. OTBDPS

OTBDPS

S

Hg(OAc)2

S

DCM, AcOH 85%

S

S S OTBDPS

6.15.1.3

O

ð12Þ

OTBDPS

Two Selenium Functions

An unusal synthesis of Se,Se0 -diphenyldiselenocarbonate has been accomplished by the reaction of dipotassium nitroacetate with benzeneselenyl bromide in 19% yield (Equation (13)) <2001CC1390>. The product is thermally unstable. K+ _ KO2C

6.15.2

O NO2

+ 2PhSeBr

ð13Þ

MeOH 1 h, 19%

PhSe

SePh

CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDE ATOM FUNCTIONS

6.15.2.1 6.15.2.1.1

Oxygen and Sulfur Functions Thiocarbonates from activated carbonates

A simple and efficient procedure has been developed for a one-pot synthesis of substituted benzothiazine-2,4-diones from thiosalicylic acid and amines. Both functional groups of thiosalicylic acid are reacted and activated, recpectively, with ethyl chloroformate affording the intermediate thiocarbonate in 62% yield (Scheme 7) <2003H115>.

Functions Containing a Carbonyl Group and at Least One Chalcogen O

O CO2H + 2ClCO2Et SH

2Et3N

OEt

O

CHCl3

437

S O

H2N

OEt

62%

O N H S O

OEt

+ CO2 + EtOH

Scheme 7

An alkyl chloroformate has also been employed to form thiocarbonates from thiols for the ‘‘desymmetrization’’ of 2,20 ,6,60 -tetramethoxybiphenyl by a regioselective sulfenylation reaction <2001TA3313>. This provides an access to C2-symmetric sulfur derivatives. Resolution of 2,20 ,6,60 -tetramethoxy-3,30 -dimercapto1,10 -biphenyl was achieved by conversion to the corresponding dithiocarbonate diastereomers. During the synthesis of potential plant protecting compounds on basis of 2,3-didehydrothiazole2-thione, isobutyl chloroformate has been used to acylate the tautomeric form of the thione catalyzed by lead nitrate affording the corresponding thiocarbonate in 89% yield (Equation (14)) <2000JPR554>. But

H N

S S

6.15.2.1.2

+ ClCO 2Bui

Cat. Pb(NO3)2

But

N S

DCM, Et3N 89%

OBui

S

ð14Þ

O

Thiocarbonates from alkoxycarbonylsulfenyl chlorides

For synthesis of the two conformationally different ‘‘tetrathiacyclododecino tetraindoles’’ the intermediate 3,30 -bis(methoxycarbonylsulfenyl)-2,20 -biindolyl has been prepared from 2,20 bisindolyl- and methoxycarbonylsulfenyl chloride in excellent yield of 94% (Equation (15)) <2002EJO1392>. Reaction occurs at rt within 2 h and needs no Friedel–Crafts catalyst. OMe O H N N H

S

MeO2CSCl DCM, rt, 2 h 94%

H N

ð15Þ N H

S

O

MeO

6.15.2.1.3

Thiocarbonates from carbonothioic acid salts

As described above, S-methyl O-benzyl carbonothioates with substituted phenyl groups have been prepared by carbonylation of benzyl alcohols with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of DBU followed by esterification using methyl iodide in good yields (Equation (16)) <2002T10011>.

438

Functions Containing a Carbonyl Group and at Least One Chalcogen

OH

+ CO + S

O

i. DBU, THF 1 MPa CO 80 °C, 6 h

S

O

ð16Þ

ii. MeI 20 °C, 16 h 89%

6.15.2.1.4

Other methods

Benzimidazo[1,2-c]quinazoline-6(5H)-thiones were prepared by cyclization of 1,2-diaminobenzene with dimethyl 2-isothiocyanatoterephthalate and acylated with ethyl chloroformate according to Equation (17) affording thiocarbonate in 70% yield <2002MI615-01>. O OEt S

N=C=S CO2Me

NH2 + NH2

MeO2C

N i. PriOH

N

ii. ClCO2Et DMF, Et3N 70%

N

ð17Þ

CO2Me

A convenient process for the synthesis of highly functionalized glyoxylic acid derivatives has been accomplished by reaction of n-butylglyoxylate with triphosgene, sodium thioethylate, and benzoic acid, to provide the acetal containing a thiocarbonate moiety with excellent yield of 91% (Equation (18)) <2002S365>. i. (Cl3CO)2CO THF, pyridine ii. NaSEt, Et 2O

O BunO O

iii. Ph-CO 2H THF, DIPEA 91%

O

SEt

O O

BunO

ð18Þ Ph

O O

According to Equation (19) a thiocarbonate is quantitatively formed from methyl 2-thioxo3H-benzoxazole-3-carboxylate with 1,6-dimethyl-2,4-hexadiene in a photochemical reaction <2002HCA2383>. O O S N

OMe S

O

6.15.2.2 6.15.2.2.1

N Photochem. Benzene, 100%

OMe

ð19Þ

O

Other Dissimilar Chalcogenide Functions Oxygen and selenium functions

During the synthesis of ‘‘mucocin,’’ a powerful antitumor ‘‘acetogenin,’’ the 4-hydroxybutenolide terminus is a key intermediate. Its precursor, the selenocarbonate, has been prepared according to Scheme 8 in a yield of 89% <1998TL9627>. Total synthesis of mucocin was achieved in an analogous way for preparing the selenocarbonate 2 (yield 78%) by using TBDPS protective group and triphosgene instead of phosgene as a carbonyl source <2002JOC5739>. In the synthesis of ‘‘(+)-juruenolide C,’’ a 5-exo-digonal radical cyclization has been applied with a selenocarbonate intermediate 3, which has been prepared in 74% yield in a similar way as described above by using carbonyldiimidazole (CDI) as a carbonyl source <2001JOC4841>.

439

Functions Containing a Carbonyl Group and at Least One Chalcogen O TBDMSO

+ TBDMSO

Se

O BuLi THF

PhSeH 89% Pyridine

O Cl

Cl TBDMSO

Ph

O

TBDMSO

Et3N

Cl

O

OH TBDMS = t-butyl dimethyl silyl

O

Scheme 8 O Se

O

Ph

TBDPSO TBDPS = t-butyl diphenyl silyl

MeO

O

OMe

O 2

O Ph

Se

O O

t Bu2SiH

O O

3

Preparation of 5-selenopentopyranose sugars from pentose starting materials by samarium(II) iodide or (phenylseleno)formate-mediated ring closures is described <2000T3995>. Selenocarbonates have been prepared by insertion of selenium into the zinc–carbon bond of arylzinc halides forming corresponding zinc selenoates which react with acyl halides in the presence of HMPA providing selenocarbonates in good yields (Equation (20)) <2002MI615-02>. O MgBr

i. ZnCl 2, THF ii. Se

Se

OMe

ð20Þ

iii. ClCO2Me HMPT 70%

6.15.2.2.2

Oxygen and tellurium functions

Alkyl aryl tellurocarbonates, which are effective precursors of oxyacyl, primary, and secondary alkyl radicals, have been prepared from diphenyl ditelluride and alkyl chloroformate in good yields (Equation (21)) <1996JOC5754>. The same tellurocarbonates can be obtained in yields of 60–96% by palladium-mediated reactions of chloroformates with aryltellurotris(trimethylsilyl)silane (Equation (22)) <1998JOC5713>.

Ph

Te

Te

Ph

i. NaBH4 MeOH, THF ii. ClCO2Me THF, 91%

O MeO

Te

Ph

ð21Þ

440

Functions Containing a Carbonyl Group and at Least One Chalcogen SiMe3 SiMe3

Si Te Ph

+ ClCO 2Me

MeO

Benzene 80%

SiMe3

6.15.2.2.3

O

Pd(PPh3)4

Te

Ph

ð22Þ

Sulfur and selenium functions

A thioselenocarbonate precursor for the synthesis of thioselenofulvalenes, which are strong electron donors, has been prepared in several steps according to the overall Equation (23) <2002JOC4218>. KCNS +

O

+ Cl-Mg

+ Se + EtSCN + CS2 + Tol-SO 2Cl 83%

O

ð23Þ I

S

S

S

Se

O

6.15.3

CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTION AND ONE OTHER HETEROATOM FUNCTION

6.15.3.1

Oxygen and Nitrogen Functions

Carbamates are carbonic acid derivatives containing a carbonyl function directly connected to an alkoxy function and an amino function. They are important for producing pharmaceuticals and polymers, and therefore many preparative methods exist. A review is given in . The formal constitution allows a great deal of variety in the alkoxy component as well as the basic amino function. In general, two synthetic approaches to carbamates can be distinguished: the first method involves a carbonic acid derivative of an alcohol or of a phenol reacting with ammonia or amine and the second one involves carbonic acid derivatives of ammonia or an amine reacting with an alcohol or a phenol.

6.15.3.1.1

Carbamates from chloroformates or phosgene equivalents

Chloroformates are easily prepared using phosgene or phosgene equivalents such as the readily available triphosgene (bis(trichloromethyl)carbonate) <1987AG(E)894, 1996S553>. 2-Methyl-2-propyl-1,3-propanediol dicarbamate (Meprobamate), a general sedative, is synthesized by the low-temperature phosgenation of the substituted 1,3-propanediol in an inert medium in the presence of a tertiary amine, followed by conversion of the bischloroformate derivative to the dicarbamate by ammoniation with gaseous NH3. Antipyrine gave consistently higher yields than other tertiary amines (Equation (24)) . i. COCl2 Antipyrine Toluene, CHCl3 OH

OH

ii. NH3 (g)

H2N

O O

O

NH2

ð24Þ

O

2-Cyclohexenyloxycarbonyl chloride has been reacted with 2-hydroxymethylaniline to provide the corresponding carbamate in 76% yield (Equation (25)) <1999AG(E)1928>.

Functions Containing a Carbonyl Group and at Least One Chalcogen H

Cl

O

OH

+

O

NH2

441

OH

Pyridine DCM

ð25Þ

NH

0 °C to rt 2 h, 76%

O

O

H

(4R,5S)-4,5-diphenyl-2-oxazolidinone has been prepared from (1S,2R)-(+)-2-amino1,2-diphenylethanol and triphosgene (Equation (26)) <1998OS45>. It is used for the synthesis of optically active amines because of its high stereoselectivity and easy deprotection by hydrogenolysis after the reaction <1993TL289>. The procedure can also be used for preparing 2-oxazolidinones from various 2-aminoethanol derivatives.

+ Ph

H2N

DCM Et3N

O

Ph

HO

Cl3CO

OCCl3

O

Ph

N H

Ph

ð26Þ

O

<10 °C, 3 h 99%

Triphosgene (1/3 equivalent) has also been employed advantageously in the preparation of 6-methoxy-2-oxo-2,3-dihydrobenzoxazole (MBOA), in yield of 75%, from 2-amino-5-methoxyphenol (Equation (27)) <1989S875>. With the exception of CDI, approaches by using other reagents—such as phosgene, urea, or potassium cyanate—employed in the reaction provide substantially lower yields of MBOA . MeO

0.33 equiv. (Cl3CO)2CO

OH

O O

2 equiv. Et3N THF, rt 30 min, 75%

NH2

6.15.3.1.2

MeO

N H

ð27Þ

Carbamates from isocyanates

Highly functionalized carbamate intermediates suitable for potential elaboration to ‘‘esperamicinone’’ have been prepared by Nicolaou employing phenyl isocyanate to react with an epoxyalcohol in excellent yield (99%) (Equation (28)) <1994T11391>. O-benzyl N-vinyl carbamate has been prepared from vinyl isocyanate and benzyl alcohol <2002OPRD74>.

O

Ph-N=C=O

O

O OH O

O

O

O

OTBDMS

DCM, Et3N 25 °C, 1 h 99%

Ph

ð28Þ

H N

O

O

OTBDMS

O

TBDMS = ButMe2Si

The first ‘‘molecular motor,’’ which consists of just ‘‘78 atoms,’’ was developed by Kelly and gets rotational energy from forming a cyclic carbamate which causes a directed movement of the rotor as shown in Scheme 9. The carbamate results from the addition reaction of the isocyanate (at the rotor) with the alcohol function (connected over a propoxy linker to the base plate) <2000JA6935, 1999NAT(401)150>.

6.15.3.1.3

Carbamates from N,N0 -carbonyldiimidazole (CDI)

CDI is widely used in the preparation of oxazolidinones. It has been employed in the synthesis of (4S,5R)-5-[(E)-dec-1-en-1-yl]-4-methyl-2-oxazolidinone (Equation (29)) <1999JOC6147, 1992JOC5469>. Further similar applications of CDI on oxazolidinones are given <2000T8643, 1998S627>.

442

Functions Containing a Carbonyl Group and at Least One Chalcogen

Me

rotor

Me

Me Baseplate

Rotation over Eact –25 kcal O

O

H N O

O

N

N

C OH O

O

O

H O

Scheme 9 O C 8 H 17

H 2N

N

N

C 8 H 17 N

N

ð29Þ

THF, 20 °C 2 h, 70%

OH

O

HN O

An elegant method for formation of N-imidazole carbamates is the reaction of alcohols with CDI which in this case is an aminocarbonylating reagent. Thus, 2,6-dimethylphenol has been reacted with CDI to result in the formation of the carbamate in good yield of 91% (Equation (30)) <2002S29>. Me

Me

6.15.3.1.4

OH

CDI

Me

DCM, reflux 5 h, 91%

O

N

N

ð30Þ

O Me

Carbamates from carbonates or dicarbonates

Diethylcarbonate is employed for the cyclocarbamation of various aminoalcohols. The reaction is catalyzed by basic substances, such as sodium methoxide, magnesium methoxide, potassium hydroxide, or sodium or potassium carbonate. Sodium methylate in xylene <1996S719>, potassium or sodium carbonate under reflux <1993TA2513, 1999EJO2965> are the preferred reaction conditions. The reaction has wide scope and synthetic utility. 4,4-Dimethyl-2-oxazolidone has been prepared with diethylcarbonate in excellent yield (98%) (Equation (31)) <1991T2801>. OH H3C NH2

H3C

O

(EtO)2CO

H 3C

K2CO3, 120 °C 2 h, 98%

O N H

H 3C

ð31Þ

Preparation of t-butyl carbamates with BOC2O from amines (and their one-pot conversion to amides with acyl halide–methanol mixture) in mostly quantitative yields has been described (Equation (32)) <2002S203>. A review on reactions of BOC2O with amines forming carbamates has appeared <2000JOC6368>.

R

1

BOC 2 O NH 2

R1 = PhCH2 (92%) n-C 8 H 17 (100%) PriOC(O)CH2 (100%) BOC = ButOCO

O Bu t

O

N H

R1

ð32Þ

443

Functions Containing a Carbonyl Group and at Least One Chalcogen

t-Butoxycarbonylation of an amidic nitrogen with BOC2O, in acetonitrile at room temperature, as part of an efficient and regioselective method for the exchange of the N-benzoyl group in Paclitaxel (Taxol1) 4 to 10-acetyldocetaxel and to Docetaxel 5 has been reported (Equation (33)) <1999TL189>. Paclitaxel1 4 and its semisynthetic analog Docetaxel (Taxotere1) 5 are among the most important new antitumoral agents of the 1990s. R2O

O

OH

O R1

NH

O

Ph

H

O

OHO AcO COPh

OH

O

4 Paclitaxel R1 = Ph, R2 = Ac 5 Docetaxel R1 = But O, R2 = H

AcO

O

O Ph

NH

OSiEt3 BOC2O, DMAP

O

Ph

O O

O

O

O

H OH O AcO

MeCN, rt, 24 h 61%

Ph Ph

O

O

OSiEt3

H

O O AcO Bn

O

O

6.15.3.1.5

O O

COPh

Bn

AcO

OtBu CO N O

Ph

O

ð33Þ

OtBu

Carbamates from carbon oxides

Carbamates can be obtained from carbon monoxide (CO) or carbon dioxide (CO2) as outlined in . A review on converting carbon dioxide into carbamato derivatives has been reported treating mainly carbamato metal complexes and their reactions <2003CRV3857>. Carbon dioxide (CO2) can be reacted with amines and alkyl halides in the presence of bases (Scheme 10) <1995JOC2820>. Use of sterically hindered guanidine bases gives best results, i.e., 80–99% yield with virtually 100% selectivity. But the need for stoichiometric amounts of base causes serious limitation to the large-scale application of the process. O

O Guanidine

R1HN

R1NH2 + CO 2

O

_

Hal-R2

R1HN

O R2 + GuanidineHHal

GuanidineH +

Scheme 10

The transformation of vicinal aminoalcohols with CO2 to the corresponding carbamates in a catalytic process that occurs in good yields has been described (Equation (34)) <2002SL307>. The catalyst is commercially available n-Bu2SnO in powder form, which is stable in air. R2 R1HN

R3 + CO2 OH

10 mol.% n Bu2SnO NMP 180 °C, 16 h

O

R3

N R1

R2

O

ð34Þ R1 = Me, R2 = R3 = H, 94% R1 = Et, R2 = R3 = H, 76% R1 = R2 = R3 = H, 53% R1 = R2 = H, R3 = Me, 73% R1 = H, R2 = R3 = Me, 85%

444 6.15.3.1.6

Functions Containing a Carbonyl Group and at Least One Chalcogen Carbazates

Generally carbazates can be divided into two groups: monoacylated and bisacylated derivatives. They are obtained simply by reacting alkyl- or aryl chloroformates with hydrazine hydrate, or with alkyl- or arylhydrazine derivatives. Chloroformate as an intermediate is employed in the reaction of 3-chlorophenol, diphosgene, and hydrazine (Equation (35)) <1998CCC793>. OH

Cl

H N

O

Cl

i. Cl 3COCO–Cl

NH2

ð35Þ

O

ii. N 2H4, Et2O 88%

Instead of chloroformates, unsymmetrically substituted O-alkyl O0 -phenylcarbonates can be used; the phenoxy group activates the carbonate ester <1968HCA622, 1984CJC574> (Equation (36)). In special cases, dialkylcarbonates, particularly the symmetrical ones, have been employed to achieve carbazates in good yields (Equation (37)) <2002CJC1187, 2000GEP19837070>. H N NH2

O Ph O

ð36Þ

O

H2NNH2

O

O O O

6.15.3.1.7

N H

O

HO

DCM 77%

Ph

O

Ph

H2NNH2

O

NH2

ð37Þ

Azidoformates

The chloroformates to be used for the synthesis of azidoformates can be generated in situ from an alcohol and phosgene <1991JCS(P1)37> or a phosgene equivalent such as diphosgene <2001JOC6585> or triphosgene <2003T8233, 2002SL1455>. A synthesis of fused 2-pyrrolines via thermolysis of 6-substituted 3,5-hexadienylazidoformates is described <2001JOC6585>. During a total synthesis of a penicillin N analog the intermediate azidoformate has been prepared by using triphosgene as shown in Equation (38) <2003T8233>. i. (Cl3CO)2CO Pyridine CCl4, 50 °C

S HO

6.15.3.2 6.15.3.2.1

H

ii. NaN3, DMF 50 °C, 67%

CO2Et

S N3

ð38Þ O

O

H

CO2Et

Oxygen and Phosphorus Functions Phosphinecarboxylates by the Arbuzov reaction and related methods

Alkyldialkyloxyphosphinecarboxylate oxides are prepared by reacting alkyl chloroformates and trialkyl phosphites in a typical Arbuzov reaction (Equation (39)) <1998T12233>. O

O (EtO)3P +

Cl

OEt

91%

EtO EtO P

OEt

+ EtCl

ð39Þ

O

Alkoxycarbonyl-substituted t-butylmethylboranes have been synthesized from the reaction of t-butylphosphine with an alkyl chloroformate, methyl iodide, and borane/THF in yields of 61–85% (Equation (40)) <2002BCJ1359>. Also disubstituted derivatives have been prepared in yields of 86–99%.

Functions Containing a Carbonyl Group and at Least One Chalcogen

445

O But-PH2 +

BH3-THF

+

MeI

+ Cl

O

67%

BuLi, THF Hexane

ð40Þ O H3B P

But

6.15.3.3 6.15.3.3.1

O

Oxygen and Other Heteroatom Functions Oxygen and boron functions

Tricyclohexylphosphine(methoxycarbonyl)borane has been prepared from the reaction tricyclohexylphosphine-iodoborane with DMC as carboxylating reagent (Equation (41)) <2000JA6329>. i. (p-But-C6H4)2*Li TMEDA, THF

c-Hex3 P I + Me2CO3 (i)

H B H

c-Hex3 P Br

O

ð41Þ

B

ii. Br 2, MeOH

OMe

H

As a synthon for novel ‘‘carboranyl peptides,’’ water-soluble icosahedral carboranyl anions have been synthesized by the above methods <2002CCC1095>.

6.15.3.4 6.15.3.4.1

Sulfur and Nitrogen Functions Thiocarbamates from chlorothioformates and amines

A simple and efficient procedure has been developed for a one-pot synthesis of benzothiazine2,4-diones directly from thiosalicylic acid and amines; the reagent for supply of the carbonyl group is ethyl chloroformate (Equation (42)) <2003H115>. NH2 CO2H

O

+

+

SH

6.15.3.4.2

OEt

Cl

O CHCl3

Ph

N

Et3N 66%

S

ð42Þ

O

Thiocarbamates from carbamoyl chlorides and thiols

A synthesis of S-2-cyclohexenyl N-dialkyl thiocarbamates is described (Equation (43)) <2002OL4217>. SH

O

i. NaH, THF

+ Cl

Ni-Pr2

ii. H2O, 82%

Ni-Pr2

S

ð43Þ O

Thiocarbamates can also be prepared from carbamoyl chlorides and disulfides which are reductively acylated in the presence of Yb metal and a catalytic amount of MeI (Equation (44)) <2002JCR(S)442>.

446

Functions Containing a Carbonyl Group and at Least One Chalcogen O O S

O

N

O S

Br

N

S

O N

Yb Cat. MeI

Cl

N

HMPT THF 83%

S

+

O

Br

ð44Þ

O S

O Br

6.15.3.4.3

Thiocarbamates from isothiocyanates and alcohols

An example for the synthesis of a thiocarbamate by reaction of an isothiocyanate with an alcohol is given <2002JGU1146>. The primary generated thioncarbamate undergoes thione–thiol (Newman–Kwast) rearrangement providing the thiocarbamate. According to Scheme 11 this immediately reacts intramolecularly to afford the 4-phospha-1,3-thiazolidin-2-one. S

EtOH

S

H N

S=C=N P OPh

Rearr.

S P

OEt

OPh

S P

S

Et

Cl

Cl

H N

O

27%

OPh

H N

O

–EtCl

Cl

S P

S

OPh

Scheme 11

6.15.3.4.4

Thiocarbamates from alkylamide salts, carbon monoxide, and sulfur

1,3-Thiazolidin-2-one has been prepared from 2-aminoethanethiol, elemental sulfur, and carbon monoxide in good yield of 87% (Equation (45)) <2002T7805>.

SH

H2N

6.15.3.4.5

S8, K2CO3 DMF, O2

H N

87%

ð45Þ

O

+ CO S

Thiocarbamates from [3,3]-sigmatropic rearrangement

2-Cyclohexenol reacts with methyl isothiocyanate via Newman–Kwast rearrangement to form S-2-cyclohexenyl N-methyl thiocarbamate (Equation (46)) <2002EJO2970>. OH

NHMe

S

i. NaH, THF

+ Me-N=C=S O

ii. NaHCO3 H2O, 80%

ð46Þ

A series of isothiocyanate-substituted allenes has been prepared by [3,3]-sigmatropic rearrangement of the corresponding propargyl thiocyanates. Further reaction of the isothiocyanate allenes provides a substituted 1,3-thiazolin-2-ones; an example is given in Equation (47) <2002S1423>. S=C=N

MeOH H2O 32%

S=C=N

OMe

H N

O

ð47Þ

S Et

Functions Containing a Carbonyl Group and at Least One Chalcogen 6.15.3.4.6

447

Thiocarbamates from trichloroacetyl chloride, thiols, and amines

It has been found that the carbonyl group in trichloroacetic acid esters behaves like one in carbonic acid ester, i.e., it can be reacted twice with nucleophiles. This is exploited for a simple two-step synthesis of thiocarbamates from trichloroacetyl chloride, thiol, and amine <2003JOC3733>. Either trichloroacetyl chloride can be reacted first with an amine and then with a thiol, or first with a thiol and then with an amine (Scheme 12). The latter method provides significantly better yields of 83–100% for thiocarbamates.

O

Cl3CCOCl

R1-SH

R1

HNR2R3

CCl3

S

83–100%

O R1

O

N

R3

1

Cl3CCOCl

Et2NH

R2 S

54–63% R -SH NEt2

CCl3

R1 = n-Hex, Ph, p-ClBn R2 = H, Et R3 = H, Et, But

Scheme 12

6.15.3.5 6.15.3.5.1

Sulfur and Phosphorus Functions Phosphonothioformates

Trialkylphosphonothioformates have been prepared in a mild one-pot reaction by sequential reaction of phosgene with alkanethiols, and subsequent Arbuzov reaction with trialkyl phosphites in good yields (Equation (48)) <2000SL815>. i. Toluene n-PrSH Et3N, DCM

O Cl

6.15.3.6 6.15.3.6.1

Cl

O +

P(OEt)2

S

ii. P(OEt)3 Toluene 84%

ð48Þ

EtCl

O

Other Mixed Systems Selenium and nitrogen functions

A ring-closure reaction has been performed using elemental selenium, carbon monoxide, and alkyl(prop-2-ynyl)amines resulting 5-alkylideneselenazolin-2-ones stereoselectively via cycloaddition of the in situ generated carbamoselenoates to the carbon–carbon triple bond <2002JOC6275>. Yields are 58–95% of product (Equation (49)). Butyl(but-3-ynyl)amine affords the corresponding six-membered selenium-containing heterocycle (69% yield) with the aid of CuI <2002JOC6275>. HN Se + CO +

R

O i. DBU, THF rt, 1.5 h ii. Sat. NH4Claq rt, 5 min

Se

N

R

R

Me Pri Bu c-Hex

Product yield (%)

78 58 95 76

ð49Þ

448

Functions Containing a Carbonyl Group and at Least One Chalcogen

Also N-heterocyclic carbamoyl chlorides have been employed in the synthesis of carbamates. Thus, N-(phenylselenocarbonyl)oxazolidin-2-one has been prepared with 85% yield by treatment of the Li salt of oxazolidinone with triphosgene, followed by addition of PhSeH <1999SL1657> (Scheme 13). Cl

O H N

i. BuLi

O

N

ii. (Cl3CO)2C=O

O

N

O 85%

O

SePh

O

PhSeH Pyridine

O O

Scheme 13

The samarium-iodide-mediated reaction of N-chlorocarbonyl-imidazolidin-2-one-N0 -methansolfonamide with dinaphthyl diselenide provides the corresponding naphthylselenocarbamate in 82% yield via the samarium selenolate RSeSmI2 <2002JCR(S)168> (Equation (50)).

O

O S

N

O

O Cl

N

+

Se

Se

SmI2 THF

O

O

O S

O

N

N

Se

ð50Þ

82%

An easy access to benzoselenazine-2,4-diones has been described <1995AJC1221>. N-butylbenzamide has been reacted with dibenzyl diselenide to provide 2-benzylseleno(butyl)benzamide, which has been treated with trimethylsilyl triflate. Resulting N-TMS-benzamide is further reacted with phosgene to afford 3-butyl-2H-1,3-benzoselenazin-2,4(3H)-dione in 80% yield (Scheme 14). O

O i. BuLi

N H

N H

ii. (BnSe) 2

Se Bn rt, overnight

TMS-Tf O N Se

O

COCl2 rt, 12 h O

N Se TMS

80%

Bn

Scheme 14

A rather exceptional access to selenocarbamates with potential antiviral properties is the treatment of an isocyanate with LiAlHSeH and the alkylation of the resulting selenide by an alkyl halide <2002JOC486>. Thus, Se-methyl N-phenylselenocarbamate has been prepared in 70% yield (Equation (51)).

Ph

i. LiAlHSeH THF, rt, 1 h N=C=O ii. MeI, rt, 2 h 70%

O Ph

N H

Se–Me

ð51Þ

Functions Containing a Carbonyl Group and at Least One Chalcogen 6.15.3.6.2

449

Tellurium and nitrogen functions

A method using very simple starting materials for the preparation of tellurocarbamates employs elemental tellurium and carbon monoxide together with amines and alkyl halides <1993HAC471>. Thereby the corresponding lithium amides react with tellurium under atmospheric pressure of carbon monoxide to yield carbamotellurates, which are trapped with alkyl halides to obtain the tellurocarbamates (Scheme 15). Satisfactory yields of above 60% can only be achieved, if the correct order of reaction steps is maintained

NH BuLi THF –78 °C

NLi

i. Te ii. CO (1 atm), 2 h iii. EtBr, 1 h

O N

Te

THF –78 °C 65%

Scheme 15

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452

Functions Containing a Carbonyl Group and at Least One Chalcogen Biographical sketch

Heiner Eckert was born in Munich, Germany, where he did his diploma in chemistry at the Technical University of Munich (TUM) in 1973, and received his Ph.D. with ‘‘summa cum laude’’ under Prof. Ugi three years later. In 1977 he founded ‘‘Dr. Eckert GmbH,’’ a company specializing in developing fine chemicals and processes for chemical production (phosgenations). At present he is working as an Academic Director at the TUM, with his research focused on new methods in organic syntheses development. Dr. Eckert has published numerous scientific papers and patents (natural product syntheses, metal phthalocyanines as reagents and catalysts), and indeed the ‘‘Eckert hydrogenation catalysts’’ are named after him. In 2003, he published the voluminous book Phosgenations–A Handbook.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 429–452

6.16 Functions Containing a Carbonyl Group and Two Heteroatoms Other Than a Halogen or Chalcogen O. V. DENISKO Chemical Abstracts Service, Columbus, OH, USA 6.16.1 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGENS OR CHALCOGENS) 6.16.1.1 Carbonyl Derivatives with Two Nitrogen Functions 6.16.1.1.1 Reactions with isocyanates 6.16.1.1.2 Reactions with metal cyanates 6.16.1.1.3 Carbonylation of amines 6.16.1.1.4 Substitution reactions of amines with phosgene and its equivalents 6.16.1.1.5 Oxidation of thioureas and related compounds 6.16.1.1.6 Reactions of amines with amides and other carboxylic acid derivatives 6.16.1.1.7 Miscellaneous reactions 6.16.1.1.8 Preparation of carbamoyl azides 6.16.1.2 Carbonyl Derivatives with One Nitrogen and One P, As, Sb or Bi Function 6.16.1.2.1 Carbonyl derivatives with one nitrogen and one phosphorus(III) function 6.16.1.2.2 Carbonyl derivatives with one nitrogen and one phosphorus(V) function 6.16.1.2.3 Carbonyl derivatives with one nitrogen and one arsenic function (carbamoyl arsines) 6.16.1.2.4 Carbonyl derivatives with one nitrogen and one antimony function 6.16.1.2.5 Carbonyl derivatives with one nitrogen and one bismuth function 6.16.1.3 Carbonyl Derivatives with One Nitrogen and One Metalloid (B, Si, Ge) Function 6.16.1.3.1 Carbonyl derivatives with one nitrogen and one boron function 6.16.1.3.2 Carbonyl derivatives with one nitrogen function and one silicon function (carbamoyl silanes) 6.16.1.3.3 Carbonyl derivatives with one nitrogen and one germanium function (carbamoyl germanes) 6.16.1.4 Carbonyl Derivatives with One Nitrogen and One Metal Function 6.16.1.4.1 Carbon monoxide insertion reactions 6.16.1.4.2 Aminative carbonylation 6.16.1.4.3 Amination 6.16.1.4.4 Reactions with heterocumulenes (isocyanates, ketenimines, azides, carbodiimides) 6.16.1.4.5 Miscellaneous reactions 6.16.2 FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS, ARSENIC, ANTIMONY, OR BISMUTH FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGEN FUNCTIONS) 6.16.2.1 Carbonyl Derivatives with Two P, As, Sb, or Bi Functions 6.16.2.2 Carbonyl Derivatives with One Phosphorus and One Metal Function 6.16.2.3 Carbonyl Derivatives with One B, As, Sb, or Bi Function, and One Metal Function 6.16.3 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (AND NO HALOGEN, CHALCOGEN, OR GROUP 5 ELEMENT FUNCTIONS) 6.16.3.1 Carbonyl Derivatives with Two Silicon Functions 6.16.3.2 Other Carbonyl Derivatives with Two Metalloid Functions 6.16.3.3 Carbonyl Derivatives with One Metalloid and One Metal Function 6.16.4 CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

453

454 454 454 460 460 461 466 466 467 468 468 468 469 470 471 471 471 471 472 473 473 473 474 474 475 476 476 476 478 479 479 479 480 480 481

454 6.16.1

Functions Containing a Carbonyl Group and Two Heteroatoms FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGENS OR CHALCOGENS)

6.16.1.1 6.16.1.1.1

Carbonyl Derivatives with Two Nitrogen Functions Reactions with isocyanates

(i) Additions of amines to isocyanates with formation of acyclic ureas (a) Starting materials. The addition of various amines to isocyanates (Equation (1)) represents the most widely used approach to the preparation of mono-, di-, and trisubstituted ureas and their functionalized derivatives, especially if the starting isocyanates are readily available. R1 N C O

O +

2 3

R R NH

R1

N H

N R3

R2

ð1Þ

As an amine component, ammonia <1994S56>, primary aliphatic amines <1999JOC2835, 2001MI351, 2003TL2065>, secondary aliphatic amines <2002PS(177)1303> and their silylated <1996JGU349> and labeled <1993MI655> analogs, cycloalkyl <2001JCO171> and cycloalkenylamines <2001CPB391>, polyaza macrocycles <2001EJO1943>, hydroxyalkyl amines <2001JMC2344, 2001MI191>, N-hydroxylamines <2000MI115723> and their O-alkyl derivatives <1992BAU1920, 1996TL5835>, amino acids <1997TL4603, 2000TL1487>, allylic amines <1993SC2065>, benzylic amines <1998TL1121, 1999JOC2835, 2000PHA490, 2003TL2065>, arylamines <1996JMC1243, 1997SL1184, 1999JOC2835, 2003MI425>, heteroaryl amines <1995JHC13, 2000BAU1202, 2001CPB391, 2001JCS(P1)2012, 2002CPB1379, 2002JMC2994>, heterocyclic saturated <1996SC3685, 1997HCA966, 1998JCS(P1)3127, 2002HCA2458> and partially hydrogenated amines <1992JHC1189, 2003SC1449>, azaheteroaromatics <1995SL605>, heterocyclic ammonium and aminophosphonium salts <1993H(35)1237, 1994JOC7144, 2002JOC5527>, aminophosphonates <1993PS(85)161, 1994OPP357, 2002PS(177)1303>, diamines <2001PHA361, 2002MI81, 2002ZN(B)937, 2003JMC1112>, polyamines <1995CL759>, amino-substituted calixarenes <1995JOC6448, 2000MI1152, 2002T7207>, steroidal amines <2002OL4639>, amino sugars <1993T2655, 1993T2676, 2002SL1779>, nucleosides <1995BSB411>, amino borabicyclononanes <1992HAC245>, cyano imines <2002JOC5546>, sulfimines <1999H(51)2035>, metalated acrylamides <2001JGU1953>, N-arylsulfonyl sulfenamides <2001JOU1611>, sulfonamides <1994AP819, 1998EUP879816, 2001MI127, 2001MI404>, hydrazines <1994H(38)235, 1994JOC6487, 1996SC2941, 2001JMC1475, 2001MI42>, N-amino indoles <2001SL222>, hydrazides <1994AP469, 2000PHA490, 2001JMC1475, 2001MI180>, carbamates <1999TL6545>, isoureas <1995AP393>, isothioureas <1996TL1945, 2002JCO285>, thiourethanes <1992JOU1635>, guanidines <2002H(57)1799>, triazenes <2000JCO710>, and even amino ligands of organometallic complexes <1994JOM(465)297> were used successfully. Along with amines, isocyanates could also be used to introduce one or more functional groups in the urea molecule. Due to the mild reaction conditions generally used, the reaction is tolerant to a wide variety of functionalities, and urea preparation from ammonium isocyanate <1993GEP4127562>, alicyclic <1995BSB411>, N-acyl <1993JGU1675, 1996SC2941> and unsaturated acyl isocyanates <1994H(38)235>, polyfluorinated <2000BAU1202>, polyunsaturated <1994S56, 2003JOC5512>, azido- and diazine-substituted isocyanates <1993MI655>, glucosyl and glucopyranosyl <1994SL919, 1995JCS(P1)377, 2000SL1253, 2001JOC4200, 2002SL1779>, phosphoryl and thiophosphoryl isocyanates <1996JGU349>, radiolabeled <2002MI785>, chlorinated <1992JOU1635, 2001MI351>, chlorosulfonyl <1996JHC943, 1996JMC1243>, arylsulfonyl isocyanates <2001WOP23368>, and isocyanato-substituted carboranes <1996POL4355, 1997IC4753> has been reported. Reaction of disubstituted silaazacyclohexanes with isocyanate-terminated polyurethane prepolymer afforded oligomeric silylureas useful as sealants <1994WOP14820>. The addition of bulky 4-(triphenylmethyl)aniline to linear isocyanates at 40 C in the presence of a macrocyclic host allowed for the preparation of nonpolymeric rotaxanes with urea-containing axles <1997SL1184>.

455

Functions Containing a Carbonyl Group and Two Heteroatoms

(b) Chemo-, regio-, and stereoselectivity of the addition. The chemoselectivity of the CuClcatalyzed carbamoylation of ergoline carboxamide 1 (Figure 1), bearing two reactive nitrogen atoms is determined by the nature of the ligand used <1995SL605>. Thus, the best ligand for carbamoylation of the indole nitrogen was found to be triethyl phosphite, whereas the chemoselectivity was reversed in the presence of 2,20 -bipyridyl. O

H N

H NMe2 N H

H

N

1

Figure 1 Ergoline carboxamide: two reactive nitrogen atoms.

3-Amino-1H-1,2,4-triazole, also having two potential reaction sites, reacts with substituted benzylic isocyanates exclusively at the ring nitrogen with the amino substituent remaining intact <2002MI109>. A similar trend was observed on carbamoylation of 2-arylaminothiadiazolidinium chloride <1993H(35)1237>. 2-Substituted 1-methylperhydropyrimidines 2 (R1 = Me, Et, i-Pr, Ph), existing in equilibrium with minor, but more reactive open-chain tautomers, N-[3-(methylamino)propyl]imines, react with isocyanates R2NCO (R2 = t-Bu, Ph, Bn) producing either ureas 3 or 4 (Scheme 1) <1997HCA966>. The chemoselectivity depends mostly on the bulkiness of the R1 substituent with smaller R1 substituents favoring the cyclic products 3. R2NCO

Me

N

N R1

NHR

R2NCO

2

N

Me

N

R2HN

H

O

3

N

N Me

R1

R1

O

2

4

Scheme 1

The reactions of isocyanates with ,-unsaturated amines bearing -hydrogen, such as 2,2-diamino acrylonitriles <1994JHC329> or N-monosubstituted -aminovinyl trifluoromethyl ketones 5 (Scheme 2) <2000TL10141, 2003T1731>, give either C-addition products e.g., 6, or ureas e.g., 7, with the nature of the predominating product depending both on the reactant substitution and the reaction conditions. Generally, the increase in the steric hindrance caused by N-substituents or those in the -position to the amino group or higher reaction temperatures favor the formation of the C-addition products, whereas the use of more polar solvents and addition of nucleophilic catalysts (pyridine, triethylamine) shifts the equilibrium toward the ureas. The effect of isocyanate component variation is less pronounced. Ts NH

O R2

H N

TsNCO CF3

2

R

H N

CF3 1

R1

O 6

Ts NH

O TsNCO

O

R

5

R2

N

CF3 R1

O

7

R1 = H, Me, Ph; R2 = H, Me, t-Bu, PhCH2, etc.

Scheme 2

The similar effect of the N-substituents was observed in reactions of acyl or phosphoryl isocyanates with 2-amino-1-propenyl phosphonates <1993JGU1675>.

456

Functions Containing a Carbonyl Group and Two Heteroatoms

When optically active amines or isocyanates are used, the reaction proceeds without racemization affording optically active ureas and their derivatives <1994JOC6487, 2000M463, 2001JOC4200>. (c) Experimental techniques and solid-phase synthesis. A series of 1,3-diaryl ureas was conveniently prepared in 80–93% yields by addition of anilines to 2-nitrophenyl isocyanate under microwave irradiation conditions <2003MI425>. An automated solution-phase parallel synthesis approach has been successfully implemented for the preparation of numerous urea libraries. To eliminate the major problem of this approach, time-consuming work-up and purification, a series of scavengers, both small-molecule and on a solid support, has been developed. Thus, excess of an isocyanate could be effectively quenched using a fluoro-tagged primary amine <1999JOC2835>, aminomethyl polystyrene <1998JCS(P1)3127> or microgel-supported tris(2-aminoethyl)amine <2002JCO436> and removed from the reaction medium by simple phase-separation or filtration, respectively. On the other side, the excess of an amine could be readily removed with fluoroalkyl-substituted isatoic anhydride or isocyanate <2003TL2065>, while the control over the unwanted amine presence could be carried out using ‘‘self-indicating’’ resins with pH-dependent color <2003JCO632>. Lately, solid-phase synthesis has become the major approach to the preparation of urea libraries and several procedures based on either the resin-bound isocyanate <1999TL2749, 1999TL4501, 2002MI81> or the resin-bound amine component <2000JCO710, 2001JCO189, 2001SL697, 2001TL1973, 2002JCO285, 2002OL597, 2002OL4033, 2003TL811> have been developed. m- and p-Ureido-substituted arylboronic acids were readily synthesized in 65–92% yields and with >95% purity via the preliminary deactivation of the acid functionality by condensation of an aminophenylboronic acid with resin-bound diethanolamine followed by treatment of the polymer-supported boronate thus prepared with an isocyanate and mild acidic cleavage from the solid support <2002JOC3>.

(ii) Additions of amines to isocyanates with formation of cyclic ureas (a) Solution-phase reactions. Reactions of isocyanates with amines, bearing a suitably located additional functional group sensitive to nucleophilic attack, are often followed by the intramolecular reactions of the nitrogen atom of the newly formed urea fragment with formation of five- or six-membered cyclic ureas. These ring closure reactions could be further subdivided into substitution and addition reactions, the former being more widely exploited. This isocyanate addition/intramolecular substitution approach generally uses - or -amino acids and esters as amine components, and the ring closure step includes intramolecular acylation of the newly formed urea fragment (e.g., Scheme 3). This procedure is most commonly applied to the preparation of fused polyheterocyclic systems <1993JHC897, 1993S111, 1994CPB2108, 1994JHC77, 1994JHC1569, 1994JOC1583, 1996TL5835, 1997WOP47626, 2002CPB1379, 2002JHC417, 2003JMC113>, but was also used for the synthesis of monocyclic substituted tetrahydropyrimidinediones <2000TL4307>, chiral hydantoins <2003OL2555>, and 5-alkoxyhydantoins <1997JOC3230>.

COOH

HO

COOH

HO R2NCO

NH N H

R1

N reflux acetone/DMSO 30–82%

N H

R1

NHR2 O

O

H

HO

2 N R

N N H

O R1

R1 = H, Me; R2 = Me, Et, n-Pr, Ph

Scheme 3

Ethoxycarbonylhydrazones 8 of aromatic aldehydes and ketones react with 2 equiv. of an isocyanate in triethylamine with formation of intermediates 9, which immediately undergo intramolecular N-acylation/ring closure to give imino-substituted triazinetriones 10 (Scheme 4) <1998JHC261>.

457

Functions Containing a Carbonyl Group and Two Heteroatoms O

EtO R2 R1

N

R3NCO (2 equiv.)

H N

OEt

N

Et3N, rt

O

15–79%

R1

N O R2

8

O

R3 N

NHR

R1

3

N R2

O

9

O

N

N N R3

R3 O

10 R1 = Me, Ph, 4-ClC6H4, 4-MeC6H4; R2 = H, Me

Scheme 4

On carbamoylation of 2-methylimidazoline, three equivalents of an aryl isocyanate are consumed affording hexahydroimidazo[1,2-c]pyrimidine-5,7-diones in good yields <1994BAU1430>. Intramolecular addition reactions, realized as a second step in one-pot preparation of cyclic ureas, include: (a) addition to a carbonyl group <2003JOC754>; (b) addition to a thiocarbonyl group followed by H2S elimination <2002HAC199>; (c) addition to a carboncarbon double bond of enamines <1998S967>; (d) addition to a carbonnitrogen double bond of imines <1998PHA607, 2001JCS(P1)1241>, isothiocyanates <1993IJC(B)779>, oximes <1999T475>, diazo compounds <2002JMC5448> or methyleneamines, generated in situ by retro-Mannich reaction of hexahydro-1,3,5-triazines <1995JHC995>; (e) addition to a carboncarbon <1995JHC1141> or carbonnitrogen <2000PS(160)141, 2001EJO1695> triple bond. The latter could further be followed by another cyclization reaction <1994AP469> or rearrangement <2001JCS(P1)1241> thus providing access to highly substituted polyheterocyclic systems. (b) Solid-phase synthesis. There are two major approaches to the solid-phase synthesis of heterocycles with a urea fragment. The first is based on the direct construction of the desired heterocyclic ring on the solid support using the isocyanate addition/cyclization procedures, described above for solution-phase synthesis, followed by simple cleavage from the resin. The representative examples of this approach include: preparation of quinazoline-2,4-diones from resin-bound 2-aminobenzoates <1996TL4439>, 1,3-disubstituted uracils <2000TL1487> and 1,3,5-triazine-2,4,6-triones <2002JCO484> from -amino esters, 1,3,5-triazine-2,4-diones from resin-bound guanidines <2001JCO278>, and trisubstituted triazinobenzimidazolediones from polymer-supported 2-iminobenzimidazoles <2002JCO345>. In the second approach, the acyclic urea fragment is constructed while on a solid support. The subsequent cleavage from the resin releases a reactive functional group (most commonly, carboxylic group), which intramolecularly reacts with the nitrogen atom of the urea unit affording the corresponding cyclic ureas. This approach was successfully used for synthesis of functionalized hydantoins <1996TL5835, 1997TL4603, 1998MI129, 1999TL5841, 2000TL7409, 2001TL1973>, spiro-hydantoins <2001JCO171>, tetrahydrouracils <1998MI139>, and 1,2,4-trisubstituted urazoles <2002JCO491>.

(iii) Self-condensation and cycloaddition reactions of isocyanates (a) Dimerization and trimerization reactions. Catalytic cyclodimerization and cyclotrimerization reactions of isocyanates with formation of symmetrical 1,3-diazetidine-2,4-diones 11 or isocyanurates 12, respectively, are well known (Scheme 5). The direction of the cyclocondensation depends predominantly on the catalyst and the reaction conditions used.

O

O R R N

N R

RNCO O

O 11

Scheme 5

N

N N R 12

R O

458

Functions Containing a Carbonyl Group and Two Heteroatoms

A wide variety of catalysts for high-yielding trimerization of isocyanates includes fluoride salts <1993JOC1932>, tricyclic proazaphosphatrane and its derivatives <1993AG(E)896, 1994JOC4931>, potassium or sodium piperidinedithiocarbamate under conventional or microwave heating <2000JCR(S)145>, sodium p-toluenesulfinate <2002BCJ851>, trialkyl amines <1994NKK146>, tetrasulfido tin complexes <1999OM4700>, and transition metal complexes e.g., CpCo(PPh3)Me2, in supercritical carbon dioxide <2001JOM(626)227>. Even minor changes in the catalyst composition can affect the product distribution: thus, self-condensation of PhNCO in the presence of the oxoniobocene complex [Cp*2Nb(O)OMe] resulted in exclusive formation of triphenyl isocyanurate, whereas the [Cp*2Nb(O)H]-catalyzed reaction gave a mixture of dimerization and trimerization products with the former predominating <2001JOM(634)47>. The exclusive or predominant formation of 1,3-diazetidine-2,4-diones 11 occurs either on heating without a catalyst <2001JOU1747> or under catalysis with pyridine or 2- or 4-picolines under high pressure <1994NKK146>. In the latter case, the selectivity of the dimerization increases with the increase in pressure or in amount of the pyridine catalyst, whereas polar solvents, such as acetonitrile, favor the trimeric product. The predominant dimerization of phenyl isocyanate was also observed when 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) was used as a catalyst <1994JOC4931>. The reaction of tungsten hexachloride with excess of ethyl isocyanate in dichloroethane led to insertion of three isocyanate molecules into one of the tungstenchlorine bonds furnishing the tungsten complex WCl4[(EtNCO)3Cl], which on hydrolysis gave isocyanurate 12 (R = Et) <2002MI673>. Self-condensation of isocyanates under aqueous (aq.) basic conditions affords acyclic symmetrical ureas. Thus, heating 3-alkoxyphenyl isocyanates in aq. NaOH gave the corresponding N,N0 -bis(3-alkoxyphenyl)ureas in 72–83% yields <1994CCC495>. Aromatic isocyanates were readily converted into symmetrical 1,3-diaryl ureas in 85–95% yields in aq. pyridine at 20 C <1999S1907>. (b) Other cycloaddition reactions of isocyanates. SbCl5-Catalyzed 1,3-dipolar cycloaddition of isocyanates with -chloro-substituted azo compound 13 afforded the corresponding triazolonium hexachloroantimonates 14 in moderate yields (Equation (2)) (where TMSNCO indicates trimethylsilyl isocyanate) <1993T9973>, whereas 1,3-dipolar cycloaddition of isoquinolinium arylimides, generated in situ from N-(arylamino)isoquinolinium halides, gave the corresponding triazoloisoquinolones in 87–99% yields <1998EJO379>.

Me Cl

i. SbCl 5, CH2Cl2,

Me N

N

–60 °C

Ar

Me

+ Me N N N Ar R

ii. RNCO 42–68%

–

SbCl6

ð2Þ

O 14

13

R = H (from TMSNCO), t-Bu, Ph

Ar = 2,4,6-Cl3C6H2

Heating phenyl isocyanate with nonsymmetrical azines 15 in xylene triggered two consecutive 1,3-dipolar cycloaddition reactions yielding heterocycles 16 with three fused five-membered rings (Equation (3)) <2002TL6431>. 1,3-Dipolar cycloaddition of phenyl isocyanate to -imino thioamides occurs with sulfur elimination affording 4-amino-1,3-dihydroimidazol-2-ones <1997BSF623>. O

Ph R H2C

N

OMe

C

N Me Me 15

N

PhNCO Xylene Reflux

N N

Me Me

OMe

ð3Þ

R 16 R = Me (64%), Et (68%)

The in situ 1,3-dipole generation via thermal or palladium-catalyzed ring opening of threemembered heterocycles, such as functionalized aziridines <1995JA4700, 2000JOC5887>, bicyclic aziridines <2000SL1779>, or oxaziridines <2001TL9131>, in the presence of isocyanates

459

Functions Containing a Carbonyl Group and Two Heteroatoms

presented a convenient method for regioselective preparation of substituted imidazolin-2-ones, pyrazolo[1,2-a][1,2,4]triazolones and 1,2,4-oxadiazolidin-3-ones, respectively. A similar azetidine ring opening/isocyanate cycloaddition of 2-vinyl azetidines under palladium catalysis <2001SL914> or of 2-azabicyclo[2.2.0]hex-5-enes <2003JOC1626> afforded the corresponding vinylic or azetidine-fused tetrahydropyrimidin-2-ones in moderate to excellent yields. Chiral 2-alkenyl dihydrooxazoles 17 (X = O) react with 2 equiv. of aryl and arylsulfonyl isocyanates to give nonracemic dihydropyrimidone derivatives 18 (Scheme 6) via asymmetric hetero-Diels–Alder reaction followed by the addition of a second molecule of the isocyanate to the cycloadduct <1997CC2311>. The thia analogs 18 (X = S) were obtained in the similar reactions of 17 (X = S) with tosyl isocyanate; however, cycloaddition with less reactive phenyl isocyanate afforded 1:1 adduct 19 as the sole product <1999SL1379>.

O

R1

R1

R3HN

N X

R3

2R3NCO

N

X

R2

R2

(X = S, R1 = Ph, R2 = H)

R1

= Me, Et, Ph;

R2

Ph O

N

S

55%

17

18 X = O;

N

PhNCO

25–94%

O

N

Ph

19

= Et;

X = S; R1 = Ph; R2 = H, (i-Pr)3SiOCH 2 R3 = Ph, 4-BrC6H4, Ts, etc.

Scheme 6

Other examples of hetero-Diels–Alder cycloaddition reactions with isocyanates include the preparation of benzimidazolotriazinones and benzothiazolotriazinones from the corresponding N-(2-heteroaryl) arylimines <1993SC1427> and of imidazo[5,1-d]-1,2,3,5-tetrazin-4-one (temozolomide) and analogs from 5-diazoimidazole-4-carboxamide <1995JCS(P1)2783, 2002JMC5448>. [2+2+2]-Cycloadditions of N-trimethylsilyl imine 20 with various isocyanates afforded unsymmetrical 1,3,5-triazine-2,4-diones 21 (Scheme 7) in 75–96% yields <1995S1529>. Importantly, two different isocyanates could be added stepwise allowing for introduction of different substituents on N-1 and N-3 atoms of the cycloadducts. Analogous [2+2+2]-cycloaddition of 3-aryl-3,4-dihydroquinazolines with 2 equiv. of phenyl isocyanate gave the corresponding quinazolinotriazinediones <2000EJO2105>. CH2OTBDMS

CH2OTBDMS

CH2OTBDMS CH2OTBDMS

R2NCO

R1NCO

N

TMS

R1

N

N

N O TMS

O N TMS

20

75–96%

R1

HN O

N N R1

R2 O

21

Scheme 7

Benzotriazolyl-substituted iminium chloride undergoes [1+2+2]-cycloaddition with 2 equiv. of phenyl isocyanate to give, after quenching with an appropriate nucleophile, functionalized hydantoins in moderate yields <1996JHC1935>. Conjugated heteroarylvinyl iminophosphoranes react with alkyl or phenyl isocyanates via the azaWittig-type reaction and formation of carbodiimide intermediates to afford heteroarylmethylidenesubstituted imidazoline-2,4-diones in moderate yields <1994JOC6413>. A similar approach was used for the solid-phase synthesis of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles from resin-bound 2-benzimidazolyl iminophosphoranes <2003JCO155>.

460 6.16.1.1.2

Functions Containing a Carbonyl Group and Two Heteroatoms Reactions with metal cyanates

Reactions of primary amines with sodium or potassium cyanates (Equation (4)) represent the most common method for the preparation of monosubstituted ureas. As an amine component, benzylic amines <2002JOC8827>, anilines <2000EJM879>, sterically constrained primary amines <1994TL8891>, -amino acids <2001JCS(P2)1247, 2001MC32, 2002JOC8827>, -amino acids <2001MC32>, and amino sugars <2002JCS(P1)1982> were successfully used. The kinetics of N-carbamoylation of -amino acids with potassium cyanate were studied in detail <2001JCS(P2)1247>. O RNH2

+

R

MOCN

N H

(M = K, Na)

ð4Þ

NH2

Secondary aromatic amines <2003JOC754>, hydroxylamines <1994TL6017>, and even azaheterocycles, such as 4,5-disubstituted 2,4-dihydro-1,2,4-triazol-3-ones <1995GEP4343595>, were also reacted with potassium cyanate to afford the corresponding urea derivatives. When the amine component has a suitably located carbonyl group, the latter undergoes intramolecular condensation with the newly formed urea fragment <2002JOC5527, 2003JOC754>. The reaction of KOCN with haloalkyl acrylates and methacrylates 22 gave the corresponding symmetrical ureas 23 (Equation (5)) <1993TL3857>. The presence of water is required to suppress the trimerization of the intermediate isocyanates. R

R

KOCN

O(CH2)nX

H2C O

O(CH2)nNH

H2C

aq. MeCN

O

Bu4 NBr

22

69–85%

CO 2

ð5Þ

23 R = H, Me; n = 6, 8; X = Cl, Br

Treatment of acyl or sulfenyl chlorides with silver cyanate in ether or aromatic solvents is a convenient approach to in situ generation of isocyanates which are unstable and/or not readily available. The subsequent addition of amines <1995TL6257>, N-alkoxyamines <1995JHC1625>, or hydrazines <1995PHA379> allows for the preparation of the corresponding functionalized ureas and sulfenyl carbazides.

6.16.1.1.3

Carbonylation of amines

A convenient approach to the conversion of primary and secondary amines into symmetrical ureas is the catalytic oxidative carbonylation of the amines with CO/O2 (Equation (6)). A wide variety of catalysts has been found effective for this reaction, including selenium compounds <2000MI355, 2000USP6127575>, manganese-based catalysts <1993JCA631>, resin-immobilized gold <2002JCA548>, Pd/H2SO4-modified ZrO2 <2001TL2161>, sulfur <1993HAC455>, polymersupported palladiumcopper catalyst <2000MI55>, PdI2/KI catalytic system <2003CC486>, and palladium methoxycarbonyl complexes in the presence of CuCl2 <1994JOM(470)249>. Electrocatalysis has also been applied <2001MI799>. Primary aromatic amines and secondary aliphatic amines are generally less reactive than primary alkylamines, allowing for the preparation of unsymmetrical ureas by oxidative carbonylation of primary alkylamines in the presence of excess of a less reactive amine <2001TL2161, 2003CC486>. R1R2NH

+

R3R4NH

CO Catalyst or ∆

O R1

N R2

N R4

R3

ð6Þ

High-pressure Se-catalyzed carbonylation of amines and diamines with [11C] carbon monoxide provided access to 11C-labeled cyclic and symmetrical acyclic ureas <2002JOC3687>. Treatment of N,N0 -di(t-butyl)diaziridinone with Ni(CO)4 under CO atmosphere resulted in CO insertion into the NN bond giving the ring expansion product, symmetrical N,N0 -di(t-butyl)diazetidinedione, in 75% yield <1999H(50)67>.

Functions Containing a Carbonyl Group and Two Heteroatoms

461

Instead of oxygen, iodine could be used as an oxidant. Thus, tungsten-catalyzed carbonylation of aliphatic primary and secondary amines and diamines in the presence of iodine furnished a series of acyclic <2000JMOC(A)11, 2000JOC5216> and cyclic ureas <1999OL961, 2002JOC4086, 2003JOC1615>. This reaction is compatible with acid-sensitive and fluoride-sensitive functional groups. A nitroarene, such as 3-(trifluoromethyl)nitrobenzene, was also used as an oxidant for Se-mediated conversion of primary alkylamines into symmetrical 1,3-dialkyl ureas <1995JGU88>. The ability of carbon monoxide to reduce nitroarenes to the corresponding anilines has been exploited in the preparation of 1,3-diaryl- <1993USP5198582, 2002JCA255, 2003JMOC(A)135> and 1-aryl-3-cycloalkyl ureas <2003JMOC(A)135>. Selenium is the most common catalyst for this process, although a polymer-supported rhodium catalyst has also been applied <2002JCA255>. In these reactions the nitro compound acts as both the reagent and an oxidant. The use of toxic carbon monoxide could be avoided by replacing it with CO2. Thus, 1,3-dialkyl ureas and 2-imidazolinones were successfully prepared from the corresponding amines or diamines and CO2 at 80 C using the Ph3SbO/P4S10 catalytic system <1992JOC7339>. Trisubstituted ureas were also synthesized under these conditions in moderate yields, but the attempts to prepare a tetrasubstituted urea, other than tetramethylurea, failed. This shortcoming was later overcome by carrying out the reaction in the presence of carbon tetrachloride and 1,8-bis(dimethylamino)naphthalene <2002JOC9070>. Purging CO2 into a mixture of a primary aromatic amine and DBU in pyridine or tetrahydrofuran (THF) followed by addition of the trimethylamine–sulfur trioxide complex as a dehydrating agent gave the corresponding 1,3-diaryl ureas in 23–87% yields <1995SC2467>. The analogous reaction of ammonia with carbon dioxide with removal of water using water-selective membranes allowed for the large-scale preparation of unsubstituted urea <2001WOP04085>. Heating primary aromatic or aliphatic amines with ethyl acetoacetate at 180 C in the presence of the commercially available zeolite, HSZ-360, led to carbonylative dimerization of the amines affording symmetrical 1,3-diaryl or 1,3-dialkyl ureas as the sole reaction products <1998CC513, 1999JOC1004>. The reaction presumably occurs via the intermediate formation of the corresponding acetoacetamide, which undergoes CC bond cleavage on further reaction with an amine.

6.16.1.1.4

Substitution reactions of amines with phosgene and its equivalents

(i) Reactions of amines with phosgene Despite its toxicity, phosgene is still utilized, although to a lesser degree than other carbonic acid derivatives, for the conversion of amines into ureas (Equation (7)). The reaction generally takes place in inert solvents (toluene, dichloromethane, THF) at 0–5 C in the presence of a base (aq. NaHCO3, aq. NaOH, triethylamine, etc.). O R1R2NH

+

R3R4NH

+

COCl2

R1

N R2

N R4

R3

ð7Þ

The reactions of phosgene with 2 equiv. of an amine were used for the synthesis of a variety of symmetrical ureas, including N,N0 -carbonylbis(azoles) <1996EUP692476, 1997JOC4155, 2000GEP19830556, 2002GEP10035011> and cyclic ureas, such as 4,5-diaminoimidazol-2-ones <1998EJO183>, imidazolidin-2-ones and their fused analogs <1993T4419>, tetrahydropyrimidin2-ones <2002HCA1999>, and hexahydroazepin-2-ones <1997JOC5380, 1998JOC9252>. More useful, however, is the synthesis of unsymmetrical ureas by consecutive treatment of phosgene with two different amines with in situ formation of an isocyanate intermediate. A combination of two aromatic amines <2002WOP83642>, two amino acids <2001OL2313>, or an aromatic or heterocyclic amine and O-alkyl hydroxylamine <1996TL2361, 2000CCA569> were all successfully used. 14C-Labeled phenylureas bearing photoactive azido and diazine groups were also prepared by this procedure <1993MI655>. The reaction with phosgene was also employed in the solid-phase synthesis of functionalized N-carbamoyl indolines <2000JA2966>.

462

Functions Containing a Carbonyl Group and Two Heteroatoms

(ii) Reactions of amines with carbamoyl chlorides Reactions of carbamoyl chlorides with amines (Equation (8)) are comparatively seldom used for the urea synthesis, probably due to a limited range of available carbamoyl chlorides. O R1R2NH

+

R1

R3R4NCOCl

N R2

N R4

R3

ð8Þ

Dialkyl and alkyl aryl carbamoyl chlorides were successfully used for carbamoylation of azaheterocycles, such as triazoles <2002BCJ567>, oxazolidinones <2002JA9060> and tetrazolinones <1995EUP646577>, arylhydrazines <1994S782>, and O,O0 -polyoxyethylene bis(hydroxylamine)s <1993JOU1464>, the latter being dicarbamoylated. In contrast, treatment of O,O0 -polyoxyethylene bis(hydroxylamine) with N-carbazolylcarbonyl chloride gave exclusively the monocarbamoylation product, albeit in a moderate yield <2001SL682>. Carbamoylation of pyridines affords the corresponding N-carbamoylpyridinium halides <1996EUP692473>; however, when -chloroformyl arylhydrazines 24 are used as the reactants, further attack of the free amino group at the 2-position of the pyridine ring occurs to afford [1,2,4]triazolo[4,3-a]pyridine-3-ones 25 (Equation (9)) <2001MI1135>. The analogous cyclization reaction was observed with isoquinoline and pyridazine <2002MI239>. Pyrimidine, however, was unreactive under the reaction conditions, whereas 1,3,5-triazine, thiazole, and 1,4,5,6-tetrahydropyrimidine underwent ring opening of the original heterocycle to afford functionalized 2,4-dihydro-1,2,4-triazol-3-ones in good yields. O Ar

100 °C

+

N Cl NH2

N

12 h

N

75–84%

excess

24

N Ar

N

ð9Þ

O 25

Ar = Ph, 4-ClC6H4, 4-MeC6H4

Carbamoylation of N-alkyl hydroxylamines with N-cyano-N-arylcarbamoyl chlorides followed by intramolecular addition of the N-hydroxy group to the nitrile furnished the corresponding 1,2,4-oxadiazol-3-ones in 93–98% yields <2002SC803>. Analogous tandem carbamoylation/intramolecular cyclization procedure was used for preparation of thiatetraazaindenones and -fluorenones from mercapto-substituted triazoles and benzimidazoles, respectively <2000M953>.

(iii) Reactions of amines with chloroformates Chloroformates, bearing two good leaving groups of different nucleofugicity, represent convenient reagents for step-by-step CO-linking of different amines (Scheme 8) and preparation of unsymmetrical ureas without isolation of the intermediate carbamates.

O

O 1 2

R R NH

+

Cl

R1 OR3

N R2

R4R5NH

OR3

O R1

N R2

N R5

R4

Scheme 8

The most widely used are phenyl and 4-nitrophenyl chloroformates, although some alkyl and chloroalkyl chloroformates are also applied. This approach was successfully used for the preparation of di- and trisubstituted ureas <1996SC4253, 2002JAP(K)212160>, N-carbamoyl amino esters <1996OPP173, 1997TL5335>, and N-arylcarbamoyl aminopyrazoles <2002WOP66442> and indolines <2000SC1937>. The procedure was also applied to solidphase synthesis of functionalized ureas <1994TL4055, 1996TL4439>.

Functions Containing a Carbonyl Group and Two Heteroatoms

463

When a substrate molecule has two amino groups of different reactivity, intramolecular cyclization can occur. Thus, heating pyrazolyl hydrazides 26 with trichloromethyl chloroformate gave pyrazolotriazinediones 27 (Equation (10)) <1999S453>, whereas condensation of -hydrazono selenamide with methyl chloroformate afforded selenated 1,2,4-triazine-3-one in 49% yield <2000PS(164)161>.

R O

R H N

N N H

O

+

N H

O

Cl

Ar

CCl3

Toluene

N

Reflux, 1 h 53–68%

O

O

N

26

N Ar

NH

ð10Þ

27

R = H, Cl, Br, NO2 Ar = Ph, 2-MeC6H4, 3-ClC6H4

(iv) Reactions of amines with carbamates and thiocarbamates Carbamates represent the carbonic acid derivatives most widely used in the urea synthesis and are generally prepared by partial aminolysis of chloroformates (see Scheme 8). O-Phenyl and O-tbutyl carbamates are the most popular, the latter being readily available from amines and (BOC)2O. Aminolysis of carbamates (Equation (11)) usually requires the presence of a base (triethylamine, DBU, NaHCO3, etc.) and, when necessary, can be promoted by addition of chlorosilanes <1998JOC8515, 2000JOC3239> or by heating over -Al2O3 <2000TL6347>. O R1R2NH

+

R3

N R4

O X

R5

R1

N R2

N R4

R3

ð11Þ

X = O, S

The reaction is tolerant to a wide variety of the functional groups on both the carbamate and the amine reactants allowing for the preparation of multiply functionalized ureas, including: acryloyl ureas <1993EUP556841>, hydroxy-substituted ureas <1997S1189, 2001TL1445>, polyfluorinated ureas <2000JOC1549>, arylsulfonyl <2001WOP05354> and heteroarylsulfonyl ureas <1995WOP00509, 2001MI404>, carbamoyl diamino acids <1994EUP629612>, N-carbamoyl nucleosides <1994HCA1267>, carbamoylamino glycosides <2000OL2113, 2001TL1445> and N-carbamoyl piperidines <1997S1189, 2000JOC1549>, piperazines <1996SL507>, indolines <2001JHC451, 2002TL6649>, dihydroquinolines <2000TL6387>, and dihydrophthalazines <2002JHC989>. The groups sensitive to the transformation include some amino protecting groups, such as N-benzoate <2000MI405> and N-phenoxycarboxylate <1992JOC5020>. The carbamate aminolysis has also been applied to the solid-phase preparation of N-carbamoyl dihydroquinolinones <2000SL45>, N-carbamoyl guanidines <1999JCO361>, oligoureas <2000TL1553>, and libraries of di- and trisubstituted ureas <1998JOC4802, 2002MI81>. On treatment with amines, cyclic carbamates, such as 2-oxazolidinones <1996TL1217> or 1H-thieno[2,3-d][1,3]oxazine-2,4-diones <1998T10789>, undergo aminative ring opening to afford hydroxy- or carboxy-functionalized ureas, respectively. When a reactive amino or imino function is already present in the carbamate or activated in situ by deprotection, the intramolecular carbamoylation can occur allowing for access to variously substituted hydantoins <1997TL2065, 1998CC2703, 2000T3697>, optically active polycyclic ureas <1996T8581>, triazinediones <2002HCO123>, and fused tetrazinones <2002JCS(P1)1877>. Cyclic ureas could also be prepared by intermolecular carbamoylation if the carbamate and/ or amine component have additional reactive functional groups. Thus, hydantoins 29 (Equation (12)) and their dehydro derivatives were prepared by condensation of N-BOC amines 28 having the

464

Functions Containing a Carbonyl Group and Two Heteroatoms

activated -position with imines <1996JOC428, 2001JOC2858, 2002EJO301> and nitriles <1994JHC1689>, respectively. Cyclocondensation of ,-unsaturated -amino acids or their esters with carbamates afforded uracil derivatives <1995JAP(K)0761975, 1998USP5817814>, whereas the reaction of dihydrobenzodiazepinethione with ethyl carbazate gave fused triazolobenzodiazepinones in moderate yields <2003JMC3758>. Pyrazolo[1,5-d][1,2,4]triazinones were prepared via the analogous cyclocondensation of 5-acylpyrazolyl-1-carboxylates with phenylhydrazine <2002JOU602>. R1 R R2

OMe

1

N

+

BOC

R3

s-BuLi THF or Et2O

N

–78 °C 22–92%

28

R2

R3

N

N OMe

O

ð12Þ

29

R1 = Ph, R2 = 4-MeOC6H4 R1 = benzotriazol-1-yl, R2 = PhCH2 R3 = Ph, 4-MeOC6H4, 2-furyl, etc.

Aminolysis of S-methyl alkylthiocarbamates with primary or secondary alkyl and cycloalkyl amines in acetonitrile <1998TL3609>, or with primary sulfonamides in toluene in the presence of DBU <2000SC3081>, gave the corresponding ureas and sulfonylureas in 60–89% yields without racemization. Although benzamide and thiobenzamide were unreactive under these conditions, aryl-substituted ureas were prepared in 81–100% yields by treatment of thiocarbamates with generated in situ aniline carbanions <2000SC1675>. Aminolysis of S-allyl N-acylthiocarbamates with a variety of amines in benzene-water twophase system <1993CCC575> or with phenylhydrazine in benzene <1993MI64> afforded the corresponding acyl ureas and acyl semicarbazides, respectively. Thermolysis of N-aryl carbamates at 230–240 C produces the corresponding symmetrical 1,3-diarylureas in 42–97% yields <1994RRC397>.

(v) Reactions of amines with ureas (a) Preparation of acyclic ureas via disubstitution of symmetric ureas with amines. Microwave irradiation of a mixture of an aromatic amine or phenylhydrazine with unsubstituted urea afforded the corresponding symmetrical ureas in moderate-to-good yields (Equation (13)) <1999JCR(S)710>. The addition of a suitable energy-transfer solvent, such as N,N-dimethyl acetamide, to the reaction mixture resulted in significant improvement in the product yields <2000MI24>. Primary aliphatic amines <2000MI24> and 2-aminopyridines <2001HCO233> reacted in a similar manner. O RNH2

H2N

O

Microwave

+

NH2

40–90%

RHN

NHR

ð13Þ

R = alkyl, aryl, 2-pyridyl, PhNH

However, of all the symmetrical ureas, commercially available, easily handled, crystalline N,N0 -carbonyldiimidazole (CDI) is the most widely used as a phosgene equivalent. Significantly lower reactivity of an N-carbamoylimidazole, formed after substitution of one imidazolyl group with an amine, compared to CDI itself allows one to carry out the disubstitution consecutively using two different amines or their analogs. This approach was applied in the solution-phase synthesis of optically active dipeptides <1997TL5335, 2002JA9356>, N-carbamoyltetrahydropapaverines <2002CPB1223> and 4-hydroxysemicarbazides <2000HCO55, 2002HCO321>, and in the solid-phase synthesis of unsymmetrical polyfunctional 1,3-diaryl ureas <1997BOC277>. Although N-carbamoyl imidazoles, formed from secondary amines and CDI, were found to be unreactive toward coupling with secondary amines, these intermediates could be activated by their conversion into the corresponding imidazolium salts <1998TL6267>, thus making this approach suitable for the preparation of tetrasubstituted ureas.

465

Functions Containing a Carbonyl Group and Two Heteroatoms

Instead of CDI, 1,10 -carbonylbis(benzotriazole) was used for preparation of tetrasubstituted ureas (no activation is required in this case) <1997JOC4155> and for solution- and solid-phase synthesis of dipeptides <1998TL7811>. (b) Preparation of acyclic ureas via monosubstitution of ureas with amines. Condensation of unsubstituted urea with a sterically hindered secondary amine in a strongly acidic medium <2000CHE837> or with a heteroaromatic amine, such as pyrazole, under thermal conditions <1992EUP508191> results in substitution of only one of the urea amino groups providing products of the general formula R1R2NCONH2. On treatment of N-phenylurea with a variety of amines, the unsubstituted amino group of the urea is cleaved, thus allowing access to a series of 1,3-di- and trisubstituted ureas <1992M607, 1995GEP4405056>. The same products could be prepared by reaction of 1,3-diphenylurea with amines <1993OPP600>. Analogously to the second step of the CDI aminolysis, reaction of independently prepared N-carbamoyl imidazoles with amines leads to the substitution of the imidazolyl moiety with the amino group <1994WOP06825>. Similarly, heating resin-bound 1-carbamoyl-1,2,3-benzotriazole with primary or secondary amines results in the nucleophilic displacement of the benzotriazole moiety releasing the newly formed unsymmetrical urea in the solution <2001JCO354>. (c) Preparation of cyclic ureas. The most widely used procedure for the preparation of cyclic ureas via the substitution pathway is the condensation of urea or its derivatives with diamines. Unsubstituted urea or CDI are generally used as phosgene equivalents. This approach was applied to the preparation of 2-imidazolidinones <1993T4419>, 2-benzimidazolones <2002JCO320>, tetrahydropyrimidin-2-ones <2002HCA1999>, hexahydroazepin-2-ones <1996USP5508400, 2002OL4673>, hexahydro-1,3,6-triazocin-2-one <1995EUP670316>, and macrocyclic ureas <1993USP5206362>. A series of functionalized hydantoins were synthesized from the corresponding resin-bound 1,2-diamines <1997TL931, 2001JCO68, 2002JCO175>. Instead of two amino groups, their analogs, such as amide <1993TL7953>, hydrazine <1999HCO473, 2001JHC1097>, or amidrazone <2002JMC2942> moieties, can participate in the reaction. If a second amine, used for the double aminolysis of CDI, features a suitably located carboxylic group, the in situ intramolecular cyclization of the newly formed urea can occur giving, for example, fused imidazolidinediones <1994JHC1235, 2002JHC417>. The similar intramolecular cyclization after formation of the urea fragment was used for solution-phase <2000TL1159> and solid-phase <2000TL1165> synthesis of 3-aminohydantoins and 3-aminodihydrouracils.

(vi) Reactions of amines with carbonates and thiocarbonates (a) Preparation of acyclic ureas. Similarly to reactions of ureas with amines, aminolysis of carbonates (Scheme 9) could be carried out by consecutive introduction of two different amines or their analogs allowing for access to unsymmetrical ureas and their derivatives. O

O R1R2NH

+

R3X

R1 XR3

N R2

R4R5NH

XR 3

O R1

N R2

N R5

R4

X = O, S

Scheme 9

Bis(trichloromethyl) carbonate, or triphosgene, is the most widely exploited. Using the coupling reaction with triphosgene, ureas derived from two different amino acids <1994JOC1937, 1999TL2895>, as well as 1-aryl-3,3-dialkyl ureas <1998JCR(S)442>, glucopyranosylureas <2001JOC4200>, -ureido alkylphosphonates <2000PS(160)51, 2001JCR(S)470, 2001HAC68>, carborane-substituted ureas <2000TL7065, 2001TL5913, 2002JOM(657)48>, ureapeptoid peptidomimetics <1997TL5335>, and urea-functionalized porphyrins <1998JOC2424> were all successfully prepared. This approach has also been applied to the solution-phase synthesis of tri- and tetrasubstituted ureas from polyethylene glycol-bound amines <2001BMCL271> and to solid-phase synthesis of peptide C-terminal semicarbazones <1999TL6121>.

466

Functions Containing a Carbonyl Group and Two Heteroatoms

Other symmetrical carbonates, such as dimethyl carbonate <2002GC269>, diphenyl carbonate <2001JAP(K)302640>, cyclic ethylene carbonate <1998EUP846679> and bis(1-cyclohexenyl) carbonate <1995JAP(K)06239805>, as well as unsymmetrical diaryl carbonates <1996SC331> were also used. Nitrophenyl carbonates were applied in the solid-phase synthesis of various ureas <1998TL3631> and azapeptides <2000TL3983>. Although di(t-butyl) carbonate is known to react with amines directly to give N-BOC-protected derivatives, under catalysis with 4-(dimethylamino)pyridine (DMAP) it reacts with a second equivalent of an amine to give the corresponding ureas. This procedure was successfully applied to primary aromatic <1996SL502, 2000JOC6368>, primary aliphatic amines and resin-bound anilines <1999TL8563>; however, with secondary amines only N-BOC protection was observed <2000JOC6368>. The condensation of primary alkylamines with S,S-dimethyl dithiocarbonate in methanol or without solvent at 60 C gave 1,3-dialkyl ureas <1996JOC4175>. Aromatic and sterically hindered alkylamines are unreactive, whereas dialkylamines give only monosubstituted products i.e., thiocarbamates. (b) Preparation of cyclic ureas. Condensation of carbonates with diamines leads to the formation of cyclic ureas if the diamine structure allows for nonconstrained ring closure. This procedure has been used for the preparation of benzimidazolones in solution <2001JCA91> and on the solid support <1998TL179>, quinazoline-2,4-diones <2002M1067>, and macrocyclic carborane-substituted ureas <2001TL5913>. Low-valent titanium-induced carbonylative dimerization of aryl imines in the presence of triphosgene gave substituted imidazolin-2-ones <2002SC2613>, which were also prepared via DMAP-catalyzed carbonylative cyclization of 1,2-diamines with BOC2O <2000JOC6368>. Condensation of S,S-dimethyl dithiocarbonate with appropriate diamines afforded a series of imidazolin-2-ones, tetrahydropyrimidin-2-ones, and 2-quinazolinone in moderate to good yields <1996JOC4175>.

6.16.1.1.5

Oxidation of thioureas and related compounds

Both acyclic and cyclic thioureas were readily converted into the corresponding ureas (Equation (14)) on treatment with bismuth nitrate pentahydrate in acetonitrile at reflux <2003TL591> or in phosphate buffer at 20 C <2000MI285>. The reaction is chemoselective: although thioamides are also oxidized, thiono esters and thioketones are essentially unreactive. Inexpensive, stable, and commercially available Oxone could also be used as an oxidant <2003PS(178)61>; however, in this case the excess of the reagent is required and a poorer chemoselectivity is observed. S R1

N R2

N R4

R3

Oxidant

O R1

N R2

N R4

R3

ð14Þ

Oxidation of 1,3-di- and trisubstituted thioureas was also carried out using sodium metaperiodate, sodium chlorite, and ammonium persulfate in water <1997SC2357>, whereas N-aroyl ureas were prepared via the oxidation of thioureas with bromine in chloroform (Hugershoff reaction) <1994CCC2663>. Potassium iodate (KIO3) was found to be a convenient reagent for the preparation of N-aroyl ureas <2000SC2635>, N-acylated bis(urea)s <2002SC3373>, and N,N0 -diacyl semicarbazides <2000SC3405, 2000SC4543, 2001SC1433> from the corresponding thiocarbonyl analogs. Trisubstituted glucopyranosyl thioureas were readily oxidized with excess of yellow HgO <2002TL4313>; the disubstituted analogs, however, gave exclusively bicyclic isoureas. There are few procedures specific for oxidation of cyclic thioureas. These include oxidation with mercury(II) acetate, used for the preparation of 1,3-diacylimidazolidin-2-ones <1993T4419>, and oxidation with 30% hydrogen peroxide in aq. NaOH, used in synthesis of six-membered cyclic ureas <1994JHC1569, 1999JHC1327>. Tetrazolinethiones were oxidized to tetrazolinones using unsubstituted oxirane or 2-alkyl epoxides as oxidants <1995EUP643049>.

6.16.1.1.6

Reactions of amines with amides and other carboxylic acid derivatives

Ruthenium-catalyzed carbamoylation of dialkylamines <1992USP5155267> or primary aromatic amines <1997OM2562> with formanilides at 165 C give the corresponding unsymmetrical diand trisubstituted ureas in high yields. For reaction with anilines, unsubstituted formamide could

467

Functions Containing a Carbonyl Group and Two Heteroatoms

also be used. Although simple alkyl and cycloalkyl amides are unreactive, -polychloro- or -polynitro-substituted aliphatic amides readily undergo -elimination to give intermediate isocyanates, which on trapping with ammonia or primary amines afford mono- and disubstituted ureas, respectively (Scheme 10) <1992BAU891, 1994BAU821, 1994CL2299, 1994OPP357, 1999TL3235>. O

O R1

N H

R3R4NH

∆

R2

R2

R2NCO

N H

–R1H

N R4

R3

R1 = CCl3, O2NCCl2, MeC(NO2)2

Scheme 10

Curtius rearrangement of acyl azides also produces the intermediate isocyanates as urea precursors. The starting acyl azides are usually generated in situ by one of the following methods: (i) reaction of a carboxylic acid with diphenylphosphoryl azide in the presence of a base <2001MI133, 2002MI109, 2002T4225>; (ii) from acyl chlorides and sodium azide <1999S943, 2000JHC1247>; or (iii) oxidation of acyl hydrazides with HNO2 <1998JCS(P1)2377>. This approach has also been applied to the synthesis of N,N0 -disubstituted ureas from heterocyclic and aliphatic carboxylic acids and resin-bound amines <2000OL3309>.

6.16.1.1.7

Miscellaneous reactions

(i) From carbodiimides Hydrolysis of carbodiimides produces the corresponding ureas <2000CAR161>, whereas their heterocyclization with diaryl nitrones <1998SC3665> or 2-(bromomethyl)acrylic acid <1996JHC1259> yields polysubstituted 1,2,4-triazolin-3-ones and 5-methylidenetetrahydropyrimidine-2,4-diones, respectively.

(ii) Heterocycle ring–ring interconversions Variously substituted 1,2,4-triazol-3-ones were prepared by ring opening/recyclization of 2-amino-1,3,4-oxadiazoles <2002JCR(S)213> or 5-amino-1,2,4-oxadiazoles (Equation (15)) <1996JOC8397> in the presence of a primary amine. The rearrangement of arylhydrazones of 3-benzoyl-5-amino-1,2,4-oxadiazoles, however, occurs differently with formation of ureidosubstituted 1,2,3-triazoles <2002JOC8010>. Ph

H

N R1

O

N

+

R2NH2

R1 = NH2, NHMe, NMe2

MeOH 57–60%

Ph N

hν

O

N R2

N

ð15Þ

R2 = H, Me, n-Pr, n-Bu, NH2

Heating 3-(2-oxopropyl)benzothiazol-2-ones with excess of a primary amine in HClO4 affords 1-(2-mercaptoaryl)imidazolin-2-ones, readily oxidizable in air to the corresponding disulfides <2000PS(158)67>. Oxidative rearrangement of 3-arylimino-2-indolinones occurs with the ring expansion to give quinazoline-2,4-diones <2000TL5265>.

(iii) Oxidation Purines and xanthines are readily oxidized to the corresponding 8-oxo derivatives with dimethyldioxirane <1995TL2665> or bacteria <1999JCS(P1)677>, whereas oxidation of benzimidazolium salts and their N,N0 -polymethylene-bridged analogs in air affords the relevant benzimidazolones

468

Functions Containing a Carbonyl Group and Two Heteroatoms

in high yields <1994TL33, 1995TL2741>. Treatment of amidines with (diacetoxyiodo)benzene yields either 1,3-disubstituted ureas or trisubstituted acylureas depending on the reaction conditions <1997JCS(P1)2319>.

6.16.1.1.8

Preparation of carbamoyl azides

The early review on carbamoyl azides <1965CRV377> indicated three preparation methods, which are still the ones most commonly used: (a) reaction of carbamoyl chlorides with sodium azide; (b) addition of hydrazoic acids to isocyanates; and (c) oxidation of semicarbazides with HNO2. Since this review, only few reports on synthesis of the title compounds have appeared. The reaction of carbamoyl chlorides with sodium azide usually occurs under very mild conditions (aq. acetone, 0–20 C) with carbamoyl chlorides being used as such <1987GEP252824> or prepared in situ from the corresponding amine and phosgene <1995JOC321>. Treatment of chloroformyl <1985JOU1436> and -chloroalkyl isocyanates <1976JOU1140> with excess of hydrazoic acid resulted in both addition to the isocyanate moiety and substitution of the chlorine atom with the azido group affording the corresponding diazido compounds, whereas with -chloro-functionalized isocyanates no substitution reaction was observed <1985RRC317>. The isocyanate reactant can also be generated in situ by addition of hydrazoic acid to acyl ketenes accompanied by nitrogen elimination <1981JOC147, 1981JOC153> or by Curtius rearrangement of acyl azides <1986JHC1103, 1990JOC5017>. Instead of unstable hydrazoic acid, its derivatives, such as trimethylsilyl azide <1980JOC5130> or triarylbismuth diazides <1992JCR(S)34> could be used; however, in these reactions the mixtures of products are usually obtained with the product distribution depending on the reaction conditions. Other methods for synthesis of carbamoyl azides include oxidation of aldehydes with pyridinium chloroformate in the presence of sodium azide <1988SC545> and reaction of carboxylic acids with the Vilsmeier salt followed by treatment with sodium azide <1994TL2729>. The latter approach is high-yielding and applicable to the preparation of a wide variety of carbamoyl azides, including optically active substrates.

6.16.1.2 6.16.1.2.1

Carbonyl Derivatives with One Nitrogen and One P, As, Sb or Bi Function Carbonyl derivatives with one nitrogen and one phosphorus(III) function

The most common procedure for the preparation of carbamoyl phosphines is based on the phosphine addition to alkyl or aryl isocyanates (Equation (16)) <1995COFGT(6)499>. The reaction is tolerant to the presence of thiol <1973JPR471>, alkylthio <1988JGU1310>, and keto <1970JPR366> groups, and is applicable both to secondary and primary phosphines. In the latter case, however, double carbamoylation of the phosphine occurs <1988JGU28>, even for sterically hindered phosphines. R1 P H R2

+

R3 N C O

O R1

P R2

N H

R3

ð16Þ

The bulky analog of PH3, tris(trimethylsilyl)phosphine (tris(TMS)phosphine), gives with isopropyl isocyanate exclusively 1:1 adduct 30, which exists in equilibrium with its (siloxy)imine tautomer 31 (Equation (17)) <1989AG(E)53>. Under mild conditions, isocyanates readily insert into the ZrP bond of PH-functionalized zirconocene complexes 32 to afford the corresponding (phosphinoamidato)zirconocenes 33 in 81–85% yields (Equation (18)). The presence of a bulky ligand, such as R1 = 5-C5EtMe4, favors the formation of complexes 33 exclusively as endoisomers (shown), whereas products 33 with less sterically hindered ligands e.g., R1 = 5C5MeH4, were formed as mixtures of endo- and exo-isomers, with exo-isomers predominating <2000OM2445>. To our knowledge, up to the early 2000s, this reaction represents the only procedure for the preparation of a secondary carbamoyl phosphine in acceptable yields.

469

Functions Containing a Carbonyl Group and Two Heteroatoms

P(TMS)3

O

Et2O, rt

Pri +

N C O

Pri

TMS

3 days

P N TMS TMS

TMS

+

OTMS Pri N P TMS

30

31

R1 O R1 Zr Cl N R3 33

Pentane, rt [R12ZrCl(PHR2)]

R3NCO

+

24 h 81–85%

R3 = i-Pr, Ph

32

ð17Þ

PHR2

ð18Þ

R1 = (η5-C5EtMe4), R2 = cyclohexyl R1 = (η5-C5MeH4), R2 = 2,4,6-Pr3i C6H2

The tertiary phosphine 34, bearing a suitably located boryl group, underwent addition to phenyl isocyanate followed by intramolecular heterocyclization to give the six-membered heterocycle 35 in 63% yield. On heating in benzene or acetonitrile, 35 readily rearranges to the bicyclic heterocycle 36 (Scheme 11) <1991BAU2099>. Ph Ph

Bu BBun2

Ph P

C6H6, rt +

PhNCO Overnight

Ph

+ Ph2P

N O

34

Bun _ MeCN or C6H6 BBu n2 ∆

Ph + Ph2P O

Ph

Bun Bun _ B Bun N Ph 36

35

Scheme 11

Another approach to the synthesis of tertiary carbamoyl phosphines, not including the reaction with isocyanates, is based on carbamoylation of secondary phosphines with carbamoyl chlorides. The only example of such a transformation, reported up to the early 2000s, is carbamoylation of bis(trimethylsiloxy)phosphine 37, which gave the desired derivatives 38 in moderate yields (Equation (19)) <1993JGU226>. O

Et3N (TMSO)2PH

+

ClCONR2

TMSO

Et2O rt, 2 days

37

52–61%

P NR2 OTMS

ð19Þ

38 R = Me, Et; R2N = morpholino, piperidino

Phenylcarbamoyl phosphine 40 was obtained as the major product of hydrolysis of azaphosphaallene 39 (Equation (20)) <1990BCJ2736>. However, the hydrolysis pathway depends dramatically on the nitrogen substituent: for example, replacement of the phenyl group on the nitrogen atom of 39 with a sterically hindered substituent, e.g., t-butyl, results in nucleophilic attack at the phosphorus atom rather than at the carbon, giving quite different sets of products. But But

P C N Ph But 39

6.16.1.2.2

H2O

But O

But

But

P H

N H

Ph

ð20Þ

40

Carbonyl derivatives with one nitrogen and one phosphorus(V) function

As in the synthesis of carbamoyl phosphines (Equation (16)), addition to isocyanates is the most common procedure for the preparation of phosphorus(V)-bearing carbamoyl compounds. As phosphorus reagents, both phosphine oxides <1983JHC331, 1991JGU622, 1995COFGT(6)499,

470

Functions Containing a Carbonyl Group and Two Heteroatoms

1996SC783, 2002HAC63> and trimethylsilylated phosphites (Equation (21)) <1987JMC1603, 1990T7175, 1995COFGT(6)499> can be utilized. The latter reaction was also applied to the synthesis of chiral phosphorus dipeptides <1987JMC1603>. The isocyanate addition can be followed by intramolecular heterocyclization to afford the corresponding phosphaazaheterocycles <1995TL2021>. Diphosphanyl ketimine oxide 41 serves as a 1,3-dipole in [3+2]-cycloaddition reaction with phenyl isocyanate resulting in formation of azaphospholene 42 in 75% yield (Equation (22)) <2002CEJ3872>. The second, also widely used, approach is the substitution reaction of alkoxycarbonyl or alkylthiocarbonyl phosphine oxides and phosphonates with nitrogen nucleophiles (Equation (23)). The reaction proceeds smoothly with ammonia <1986JMC1389, 1995COFGT(6)499>, primary amines <1988JGU26, 1998SL1325>, amino acids <1998SL1325> and diamines <2000HAC470>, and even with hydroxylamines <1997JOC3858>, although in the latter case the reaction has to be carried out in pyridine to avoid formation of the Lossen rearrangement product. A variety of functional groups, such as alcohols, esters, or amides, is tolerated. EtO

O R EtO N P O OEt H

CH2Cl2, rt

OTMS

+

P OEt

RNCO

ð21Þ

R = Ph, 87% R = 4-O2NC6H4, 86%

Ph Ph O P C C N Ph Ph P Ph

+

Ph Ph P O

Toluene

PhNCO

NPh N Ph

Ph P Ph

reflux, 10 min

ð22Þ

O

75% 42

41

O

R3R4NH

R1 R2

P O

O R1 R2

X

NR3R4

P O

ð23Þ

X = OMe, SEt, OPh

P-Carbamoylation of 3-bis(siloxy)phosphinyl propanoate 43 under mild conditions with simultaneous elimination of TMSCl gave the functionalized carbamate 44 in 87% yield (Equation (24)) <1996JGU1867>. O TMSO

ClCONMe2 P OTMS

OTMS

CH2Cl2 reflux

43

TMSO

O P

O

O OTMS NMe2

ð24Þ

44 87%

Studies on azide addition/Schmidt rearrangement of dialkyl acylphosphonates RCOPO(OR0 )2 revealed the formation of carbamoyl phosphonates RNHCOPO(OR0 )2 as the primary rearrangement products <1994JA1016>. However, the yields of these compounds depend on the substitution in the starting acyl phosphonate and usually do not exceed 20%, making this approach ineffective for the synthesis of carbamoyl phosphonates.

6.16.1.2.3

Carbonyl derivatives with one nitrogen and one arsenic function (carbamoyl arsines)

No information on the synthesis of tertiary carbamoyl arsines has been found in the literature. The data on secondary carbamoyl arsines are essentially limited to the single early article <1967LA248>, already reviewed <1995COFGT(6)499>, which reported the preparation of these compounds via Sn-catalyzed addition of alkyl, cycloalkyl, and aryl arsines or their lithium derivatives to phenyl or cyclohexyl isocyanates.

471

Functions Containing a Carbonyl Group and Two Heteroatoms

The heterocycle 46, which could be considered as pyridine-fused cyclic carbamoyl arsine, existing, however, exclusively in the hydroxy form shown (Scheme 12), was prepared in a low yield by treatment of zwitterionic pyridooxadiazole 45 with tris(trimethylsilyl)arsine followed by hydrolysis <1988TL3387>.

i. (TMS)3As, MeCN 18% N N

+ O

N N

ii. MeOH, 2 h 82%

_

O

As OH

45

46

Scheme 12

6.16.1.2.4

Carbonyl derivatives with one nitrogen and one antimony function

No compounds of this type have been found in the literature.

6.16.1.2.5

Carbonyl derivatives with one nitrogen and one bismuth function

A single article, dealing with this class of compounds, reported the formation of quaternary carbamoyl bismuthanes on treatment of dimethylformamide-BiCl3 adduct with tertiary amines <1995COFGT(6)499>. To our knowledge, no more data on such compounds has appeared in the literature since.

6.16.1.3 6.16.1.3.1

Carbonyl Derivatives with One Nitrogen and One Metalloid (B, Si, Ge) Function Carbonyl derivatives with one nitrogen and one boron function

Carbamoyl boranes are generally prepared as adducts with tertiary amines, such as trialkyl amines, pyridine, or quinuclidine, via two synthetic approaches based either on amidation of amine-carboxyborane adducts or on hydrolysis of amine-cyanoboranes. Thus, direct coupling of trimethylamine-carboxyborane 47 with primary or secondary aliphatic or primary aromatic amines in the presence of the peptide-condensing agent dicyclohexylcarbodiimide (DCC) gave the corresponding carbamoylborane adducts 48 in moderate yields (Equation (25)) <1987JCR(S)368, 1990BCJ3658, 1995COFGT(6)499>. A similar procedure was applied to the synthesis of the boron analog of hydroxamic acid using hydroxylamine hydrochloride in water instead of an amine <1988IC302>. Me3N . BH2COOH

DCC +

R1R2NH

CH2Cl2

47

Me3N . BH2CONR1R2

ð25Þ

48

rt, 3 days 60–70%

The other general approach is based on a two-step procedure including addition of triethyloxonium tetrafluoroborate to cyanoborane adducts followed by basic hydrolysis of the intermediates 49 (Scheme 13).

A . BHRCN

– Et3O + BF 4

O +

– A . RHB C N Et BF4

49

Scheme 13

aq. NaOH 50–99%

A . RHB

NHEt

472

Functions Containing a Carbonyl Group and Two Heteroatoms

Both unsubstituted (R = H) <1990IC554, 1990IC3218, 1991T6915> and monosubstituted (R = Me, i-Pr, i-Bu, s-Bu, Bn) cyanoboranes <1989CC900, 1989IS79, 1991IC1046> could be used, whereas the second component (A) of the adduct could be a tertiary amine <1989CC900, 1990IC554, 1991IC1046>, triethyl phosphite <1991T6915>, or phosphonate <1990IC3218>. The similar treatment of amine-dicyanoborane adduct afforded amine-bis(carbamoyl)boranes <1997CC1799>. Limitation of the above method to the preparation of ethylcarbamoyl boranes due to exclusive application of triethyloxonium tetrafluoroborate triggered a search for other synthetic procedures, which up to the early 2000s have been represented by single examples. Thus, addition of SbCl5 to Me3NBH2CN followed by treatment with t-butyl chloride and basic hydrolysis gives t-butylcarbamoyl borane adduct <1994POL2599>. Cyanation of diboratacyclohexane 50 with isonitrile 51 resulted in formation of the bridged salt product, which on hydrolysis with aq. NaOH gave N-unsubstituted carbamoyl boracycle 52 (Scheme 14) <1991IC2228>. H_ B I + N Me Me 50

i. CHCl3

Me + Me N _ H B H

+ _ Me3N.H2B–N C

+

ii. aq. NaOH

Me + Me N _ H B

80%

H

rt, 2 days

H_ NH2 B O N+ Me Me

52

51

Scheme 14

Reaction of pyridine-cyanoborane adduct 53 (R = CN) (Figure 2) with methyl triflate at 40 C in the absence of light gave the carbamoylborane adduct 53 (R = MeNHCO) in 19% yield <2000S1229>. On stirring in methanol at room temperature (rt), the monomeric adduct of triphenylborane with 2-(trimethylsiloxy)phenyl isocyanide undergoes dimerization/rearrangement to afford heterocyclic diborane 54 in 20% yield <1996OM1251>. _H H + B N R

S S 53

Ph _ Ph H B N O + + N _O B Ph Ph

_ O Cp*Cl3 Ta

OH

N+

SiMe3

58

54

Figure 2 Examples of carbamoyl boranes and silanes.

6.16.1.3.2

Carbonyl derivatives with one nitrogen function and one silicon function (carbamoyl silanes)

Since the early report on the preparation of the first thermally stable carbamoyl silane Me3SiCONEt2 by silylation of dicarbamoyl mercury with hexamethyldisilathiane <1995COFGT(6)499>, several approaches to the construction of the NCOSi link have been developed, most of which, however, are applicable exclusively to tertiary carbamoyl silanes and suffer from severe limitations. Up to the early 2000s unstable secondary carbamoyl silanes have been prepared only by hydrosilylation of isocyanates either with t-BuPh2Li at 50 C <1983T2989> or with Et3SiH in the presence of PdCl2 <1977JOM(140)97>. Tertiary carbamoyl silanes 56, bearing a sterically hindered aryl group at the nitrogen atom, have been prepared, albeit in low yields, via carbonylation of lithiated silyl amides 55, generated in situ from the corresponding anilines and chlorosilanes, accompanied by 1,2-Si rearrangement (Scheme 15) <1994OM1533>. Ar

Li

N SiR3 55

i. CO (30 atm.) rt, 15 mi n ii. MeI, –78 °C 17–40%

R3 = Me3, PhMe2 Ar =2,6-R′2C6H3 (R′ = Me, Et, i-Pr)

Scheme 15

O Ar

SiR3 N Me 56

Functions Containing a Carbonyl Group and Two Heteroatoms

473

Silanes 56 could also be synthesized by sequential introduction of the carbonyl and trimethylsilyl group via carbonylation of mixed cuprates followed by silylation with a chlorosilane <1994JOM(474)23>. Lithiation/silylation of formamide HCON(Me)CH2OMe afforded the corresponding carbamoyl silane Me3SiCON(Me)CH2OMe 57 in 61% yield <2001TL1423>. Although only the trimethylsilyl (TMS) group could be directly introduced by this procedure, a series of carbamoyl silanes were prepared via silyl group exchange by treatment of 57 with chlorosilanes at 145 C in the presence of CsF. Although the synthesis of carbamoyl silanes by silylation of carbamoyl chlorides seems obvious, the preparation of silanes (TMS)3SiC(O)NR2 (R = Me, Ph) from carbamoyl chlorides R2NCOCl and (TMS)3SiLi(THF)3 still represent the only example of such a transformation <1991JOM(403)293>. Carbonylation of Cp*Cl3TaSiMe3 with limited quantities of CO followed by addition of pyridine or 2,6-dimethylpyridine gives the stable Ta-carbamoyl silane complex e.g., 58 (Figure 2), bearing a quaternary nitrogen atom <1989JA149>.

6.16.1.3.3

Carbonyl derivatives with one nitrogen and one germanium function (carbamoyl germanes)

In contrast to the silicon analogs, only one example of synthesis of carbamoyl germanes using trialkylgermyl chloride has been reported up to the early 2000s <1971AG(E)339>. All the other known procedures use Et3GeLi as the germanium-introducing reagent. Thus, reaction of Et3GeLi with CF3C(O)NEt2 <1983JOM(248)51> or Me3SiCCC(O)NMe2 <1984BAU1733> under thermodynamic control conditions afforded carbamoyl germanes Et3GeC(O)NEt2 (56%) and Et3GeC(O)NMe2 (45%), respectively. The scope of the carbamoyl group-delivering reagents has been extended to carbamates (Equation (26)) <1990POL227>. Me2NCOCl could also be used in this reaction as a carbamoylating reagent; however, in this case only 0.25 equiv. of the aluminum alkoxide should be employed due to its rate-inhibiting effect. O

O Et3GeLi

N

+

OMe

X

(sec-BuO)3Al (1 equiv.) Hexane / benzene 70–80 °C

6.16.1.4.1

GeEt3

ð26Þ

X = O, 54% X = CH2, 33%

3h

6.16.1.4

N X

Carbonyl Derivatives with One Nitrogen and One Metal Function Carbon monoxide insertion reactions

One of the most widely used methods for the preparation of carbamoyl metal complexes is based on the insertion of the carbon monoxide molecule into an already existing nitrogenmetal bond (Equation (27)). The examples of organometallic compounds involved in the transformation include: cuprates <1985JOM(297)379>, complexes of nickel <2002CC1840>, iron <1992JA1256>, platinum <1985OM939>, palladium <2000OM1661>, rhodium <1988OM2234, 1992IC379>, iridium <1994OM1751>, ruthenium <1993IC3640, 1999OM187>, rhenium <1998OM131>, molybdenum <1987OM210>, tungsten <1986OM185>, thorium, and uranium <1988CRV1059, 1995COFGT(6)499>. Molybdenum or copper complexes containing more than one metalnitrogen bond, such as Mo(NMe2)4 or lithium bis(amino)cuprates, undergo CO insertion into all these bonds even under mild reaction conditions. In contrast, carbonylation of tungsten complex W2Cl2(NMe2)4 with excess of CO in toluene/pyridine gave exclusively the monoinsertion product in 69% yield <1986OM185>. O (L)n M NR2

CO

(L)n M

ð27Þ NR2

474

Functions Containing a Carbonyl Group and Two Heteroatoms

1,3-Dipolar cycloaddition reactions of (1,4-diaza-1,3-butadiene)tricarbonyliron complexes 59 (M = Fe) (Equation (28)) with electron-deficient alkynes, such as dimethyl acetylenedicarboxylate (DMAD) or methyl propiolate, in the presence of an external ligand L [L = CO, P(OMe)3] is accompanied by intramolecular insertion of a CO molecule into the metalnitrogen bond affording thermally labile bicyclo[2.2.1] adducts 60 in 60–95% yields <1985OM948, 1986JOM(302)59, 1987JOM(323)67, 1990OM1691, 1996OM2148>. R N CO M CO N CO R

R2 R +

R1

R2

+

N

L O

N M R1OC

59

L CO

R

ð28Þ

60

M = Fe, Ru

R1 = R2 = CO2Me

R = i-Pr, t-Bu

R1 = H,

60–95%

R2 = CO

2Me

Analogous reactions of ruthenium complex 59 (M = Ru, R = i-Pr) with DMAD in the presence of CO or PPh3 as external ligands have been observed <1992OM3607>. In contrast to the iron analogs, which are unreactive toward electron-deficient alkenes, ruthenium complexes 59 (M = Ru; R = Me, i-Pr) undergo cycloaddition with dimethyl maleate or fumarate to afford the corresponding adducts in 70–90% yields <1995OM4781>.

6.16.1.4.2

Aminative carbonylation

Another widely used procedure for the preparation of carbamoyl metal compounds is based on the introduction of both carbonyl and amine moieties into the organometallic compound and is generally performed by carbonylation of a metal complex in the presence of a primary or a secondary amine. Although most commonly used in the synthesis of platinum and palladium carbamoyl compounds <1985JOM(296)435, 1987JOM(334)C9, 1990OM2603, 1990OM2612, 2000OM3879, 2002MI267>, this approach has also been applied to the preparation of carbamoyl stannanes <1988JCS(P1)569>, nickel <1985AG(E)325, 1985JOM(281)379>, rhodium <1993OM3410>, ruthenium <1998JOM(563)1>, and iron <2000OM3754> complexes. A modification of this procedure includes carbonylation of metal complexes in the presence of nitrobenzene as an amine precursor <2000OM3754, 2002MI267>; however, this reaction requires significantly higher temperatures (80–160 C) compared to the one using amines (0 C–rt). Indirect aminative carbonylation is represented by the reaction of Ph3PAuCl with methyl isocyanide in aq. KOH, which afforded the unstable carbamoyl gold complex Ph3PAuC(O)NHMe, presumably via hydrolysis of the intermediate isonitrile gold complex <1999IC3494>.

6.16.1.4.3

Amination

Currently, amination of metal carbonyl complexes represents the most common approach to the preparation of metal carbamoyl derivatives and has been successfully applied to the synthesis of carbamoyl complexes of Re <1988JOM(339)111, 1997JOM(541)423>, Mo <1989IC4414, 1991OM1305, 1997OM5595>, Ir <1992JOM(441)155>, Os <2002JOM(658)147, 2002MI963>, Fe <1991IC1955, 1993OM1725, 1994CB711, 1996JCS(D)4431, 1997HCA121, 1999ZN(B)385, 2000OM15>, Mn <1991JOM(414)65>, Pd <1989OM2065, 1990JOM(383)587>, Ru <1984IC4640, 1986ICA169, 1989JOM(368)103, 1989JOM(379)311, 2001OM3390>, Co <1986OM2259, 1987CB379>, Cr <2001ZN(B)306>, W <1994OM1214, 1999OM748, 2001ZN(B)306>, and Pt <1985OM180, 1988JA7098, 1991OM175>. Both neutral metal complexes (for Mo, Ir, Os, Pt, Mn, Ru, Fe) and cationic complexes (for Fe, Pd, Co, W, Pt, Re) could be used. The reactions can be accompanied by the loss of a nonreacting ligand <2002MI963>. As nitrogen nucleophiles, both primary <1991JOM(414)65, 1992JOM(441)155> and secondary aliphatic amines <1988JA7098, 2002JOM(658)147>, cyclic amines <1988JOM(339)111, 1989JOM(368)103, 1990JOM(383)587>, aryl alkyl amines <1986ICA169>, anilines

Functions Containing a Carbonyl Group and Two Heteroatoms

475

<1986OM2259>, amino esters <1999ZN(B)385>, hydrazines <1991IC1955, 1991OM1305> and even N-substituted aziridines (with aziridine ring opening) <1997HCA121>, and N-nitrosoamines <1993OM1725> were applied. An aromatic amine could also be generated in situ from the corresponding nitroarene under reductive conditions <2001OM3390>. In a metal complex with a ligand bearing a suitably located nucleophilic nitrogen atom, intramolecular amination can occur <1990JOM(387)C5, 1996JCS(D)4431>. The outcome of the reaction with diamines is determined by the starting organometallic compound: thus, cationic (OC)5ReFBF3 reacts with both amino groups of diaminoalkanes in a standard fashion affording the corresponding dicarbamoyl-bridged 2:1 complexes <1988JOM(339)111>, whereas monoamination of (OC)5ReOSO2CF3 is followed by intramolecular attack of the second amino group at the central metal atom with formation of the cyclic carbamoylrhenium complex <1997JOM(541)423>. Tetrakis(dimethylamino)methane, C(NMe2)4, has also been used as an efficient dimethylamino group donor for the preparation of Ru <1984IC4640>, Cr and W <2001ZN(B)306> carbamoyl complexes under mild conditions. The reaction proceeds via insertion of one of the carbonyls of the metal carbonyl compound into the CN bond of the tetraaminomethane. A procedure based on a similar mechanism was applied for the preparation of a series of bimetallic complexes. Thus, reaction of carbonyl complexes M(CO)n (M = Fe, n = 5; M = Cr, Mo, W, n = 6) or Mn2(CO)10 with organometallic dimethylamides, such as Al(NMe2)3 <1987JOM(323)149>, Ti(NMe2)4 <1993JOM(456)85>, Zr(NMe2)4 <2000JOM(598)403> or Cp*M0 (NMe2)3 (M0 = Ti, Zr) <1995OM131>, gives the corresponding heterogeneous cluster compounds with M-CO-N fragment.

6.16.1.4.4

Reactions with heterocumulenes (isocyanates, ketenimines, azides, carbodiimides)

Reactions of neutral or cationic metal carbonyl complexes with isocyanates occur under mild conditions (neutral solvents, rt) and result in formation of the corresponding metallacyclic 1:1 adducts with a cycle size depending on the central metal and on the nature and reactivity of the ligands in the original complex. Thus, Cp2W(CO) gave four-membered metallacycles yielded six-membered metallacycle <1987JA2173, 1989JA7424> and Cp2V(CO) <1988JGU2384>, whereas five-membered metallacycles 62 (X = S) were obtained from cationic Fe and Ru complexes 61 and isothiocyanates (Equation (29)) <1998JOM(568)241>. Analogous reactions of the neutral complex (OC)2CpFePH(t-Bu) with isocyanates and isothiocyanates provided 62 [X = O, S; R1 = t-Bu, R2 = R3NHC( = X)] <1998JOM(568)247>. Cp R1 OC M P R2 OC H 61

+ _

A

R3NCX

t-BuOK toluene, rt 68–83%

Cp R1 M P OC R2 O

X N 3 R 62 M = Fe, Ru; X = S; A = BF4, PF6;

ð29Þ

R1, R2 = i-Pr, t-Bu, Ph; R3 = Me, Et

This approach has also been applied to the preparation of cyclic carbamoyl mononuclear manganese <1999OM2459>, cobalt <1991JOM(413)379>, iron <1987IC973> and binuclear iron <1989OM443>, iridium <1988JA8543>, and rhenium <1999OM2459> complexes. Potassium cyanate was utilized in the synthesis of five-membered carbamoyl platinacycle <1989G301>. 1,3-Cycloaddition of (5-MeC5H4)Mn(CO)2(THF) or Cp2Mo2(CO)4 with benzyl or aryl azides gave the corresponding binuclear adducts e.g., 63 (Figure 3) <1986OM894, 1987OM2151>. Cluster Os3(CO)11(NCMe) reacted similarly <1987OM2151>, whereas reactions of cobalt and rhenium phosphine complexes CpM(CO)PR3 (M = Rh, R = i-Pr; M = Co, R = Me) occurred via azide degradation followed by [2+1] cycloaddition to give metallaaziridinones 64 (R0 = Ph, Ts) (Figure 3) in 69–79% yields <1992JOM(440)389>. Metal carbonyl anions [CpFe(CO)2] and [Re(CO)5] undergo regiospecific [2+2] cycloaddition with ketenimines R1R2C¼C¼NR3 (R1 = R2 = Ph; R3 = Me, Ph) to give the isolable anionic complexes e.g., 65 (Figure 3) <1985JOM(294)251>. Under similar conditions, the carbene iron complex (CO)4Fe¼C(OEt)Ph afforded acyclic -allyl,-complexes 66 (R1 = Me, Et, i-Pr; R2 = Me; R3 = Ph) <1991CB1795>.

476

Functions Containing a Carbonyl Group and Two Heteroatoms _

Me OC

Mn N

N N Ph

CO Mn CO O

Me

Ph

Cp R3P M N R′ 64

63

O

Ph

Ph

(OC)4 Re

N Ph O

R2

CO2Et

R1 (OC)3Fe

65

N R3 O

66

Figure 3 Carbamoyl metal complexes.

The reaction of Cp2W(CO) with diphenyl carbodiimide occurs by the same route as its reaction with isocyanates to give [2+2]-cycloaddition product, imino-substituted metallaazetidinone, in 94% yield <1989JA7424>. A similar formation of formal [2+2]-cycloaddition products was observed in the reactions of CpW(CO)3H and Cp*W(CO)3H with acyclic or cyclic sulfur diimides <1985ZN(B)1233, 1989JOM(371)303, 1993CB1781>. The reactions are regioselective: in the case of monosubstituted sulfur diimides, only substituted nitrogen atom participates in the metallacycle construction. When sulfur diimides with electron-accepting substituents, such as Ts, were used, no cyclization was observed and only acyclic metalhydrogen bond insertion products were isolated.

6.16.1.4.5

Miscellaneous reactions

(i) Additions of metal carbonyls to iminophosphines and phosphine imides Treatment of Fe or Mo carbonyl complexes with iminophosphines results in ligation of the phosphorus to the metal atom followed by intramolecular attack of imine nitrogen at a CO ligand to afford the corresponding metallaphosphaazetidinones <1985JA2553, 1986OM2376>. In contrast, the analogous reactions with phosphine imides are accompanied with the cleavage of the phosphorusnitrogen bond giving metallapyrrolinone complexes in 69–72% yields <1991JA3800>.

(ii) Transmetallation Platinum and palladium carbamoyl complexes (Et2NCO)M(PPh3)2X (M = Pt, Pd, X = Cl; M = Pt, X = PPh3) were prepared in 75–87% yields by treatment of carbamoyl mercury compounds ClHgCONEt2 or Hg(CONEt2)2 with Pt(0) or Pd(0) triphenylphosphine complexes at 20 C in benzene <1980BAU1490>.

(iii) Ligand modification reactions Treatment of transition metal complexes bearing an alkoxycarbonyl ligand with primary aliphatic or benzylic amines under mild conditions results in substitution of the alkoxy group with an alkylamino fragment. The reaction was applied to the preparation of Ru <1994IC253>, Re <1992IS211> and Fe <1985JCS(P1)2375, 1985T5871> carbamoyl complexes.

6.16.2

6.16.2.1

FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS, ARSENIC, ANTIMONY, OR BISMUTH FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGEN FUNCTIONS) Carbonyl Derivatives with Two P, As, Sb, or Bi Functions

One of the few approaches to the preparation of carbonyl compounds with two phosphorus functions is based on the modification of the substituents on the central carbon of the already existing PCP fragment. Thus, the parent carbonylbis(phosphonic) diacid was prepared in

Functions Containing a Carbonyl Group and Two Heteroatoms

477

63% yield by basic hydrolysis of its dichloro derivative <1995COFGT(6)499>; however, this procedure is restricted to this particular compound. Later, a series of carbonylbis(phosphonates) 68 (Equation (30)) was prepared by McKenna and co-workers by oxidation of the corresponding -diazomethylenebis(phosphonate)s 67 with t-BuOCl. The product yields and formation of ,-dichloro-substituted by-products depend on a solvent and the presence of water, with aq. EtOAc being preferred as a solvent <1993PS(76)139, 1999PS(144)313, 2000WOP002889>. N2 O O P P OR RO OR OR 67

O O O P P OR RO OR OR

t-BuOCl aq. EtOAc 2–5 min 10–15 °C

ð30Þ

68 R = Me (93%), Et (94%) i-Pr (95%)

Another approach is based on the reaction of phosphines or their trimethylsilyl derivatives with phosgene. In this reaction, the secondary phosphines give acyclic carbonyldiphosphines <1995COFGT(6)499>, whereas primary phosphines and their silylated analogs afford four- or five-membered phosphacycles (Scheme 16) <1983CB109, 1983TL2639, 1999ZAAC1979>, presumably via dimerization of phosphaketene intermediates. O COCl2

Ph3CPH2

Et2O rt, 18 h 94%

R P

P R

COCl2 –60 °C

t-BuP(TMS)2

O R = t-Bu or Ph3C

Scheme 16

The formation of intermediate bis(phosphaketene) was also suggested for the preparation of anionic heterocycle 69 (Figure 4) by treatment of PCOLi with SO2 in dimethoxyethane (DME) at 50 C <1995ZAAC34>. Me2P Me2P –O

P

O

P P O

P 69

O–

Me2P

PMe2 P P O Th C C O P P Me2P

PMe2

PMe2

PMe2 70

Figure 4 Polycyclic phosphacarbonyl compounds.

Carbonylation of homoleptic eight-coordinated thorium dialkylphosphide Th[P(CH2CH2PMe2)2]4 in hydrocarbons afforded the double insertion product 70 (Figure 4) in 73% yield <1994CC1249>. The similar carbonyl bridge formation between phosphorus ligands was observed in reactions of sterically hindered (dialkylamino)dichlorophosphines with tetracarbonyl ferrate as the carbon monoxide source <1995COFGT(6)499>. The mechanism of this transformation, steric requirements, and substituent effects have been studied in detail <1990JOM(383)295>. Organometallic compounds bearing a PCOP unit were also prepared via carbonylative PP bond cleavage of metal diphosphine complexes. Thus, cleavage of the PP bond with insertion of carbon monoxide was observed on treatment of iron complexes 71 or 72 with CO or excess Fe2(CO)9 (Scheme 17) <1986ZN(B)283, 1991CB265> or by ring opening–ring closure of substituted cyclotetraphosphane in the presence of Fe2(CO)9 <1991CB265>.

478

Functions Containing a Carbonyl Group and Two Heteroatoms O But

But

P P (OC)3Fe Fe(CO)3 71

CO

t R P P Bu (OC)3Fe Fe(CO)3

Benzene 80 °C, 20 h

73

75%

Fe2(CO)9 THF rt, 2 days

But P P (OC)3Fe Fe(CO)3 R

72

44%

R = t-Bu, Cp*Fe(CO)2

R = Cp*Fe(CO)2

Scheme 17

Cleavage of the phosphorusphosphorus double bond followed by carbon monoxide insertion on treatment of a series of Fe, Ru, or Os diphosphene complexes with excess of Fe2(CO)9 in toluene affords the corresponding metallated diphosphinomethanone complexes, analogs of 73 <1986AG737, 1987CB1421>. No information on the synthesis of carbonyl derivatives with two As, Sb, or Bi functions, or unsymmetrical analogs has been found up to the early 2000s.

6.16.2.2

Carbonyl Derivatives with One Phosphorus and One Metal Function

The most important approaches to the preparation of carbonyl compounds with one phosphorus and one metal function are based on: (a) carbon monoxide insertion into the metalphosphorus bond; (b) formation of PCO bond via phosphinylation of metal carbonyls; (c) formation of the MCO bond via reaction of metal complexes with -keto phosphonates; and (d) carbonylative phosphinylation of metal complexes. The carbonylation approach has been successfully applied to the preparation of hafnium <1988CRV1059, 1995COFGT(6)499>, thorium 70 (Figure 4) <1994CC1249>, and zirconium complexes <1996OM1134> under mild conditions. A series of phosphinocarbonyl complexes 75 was synthesized by reaction of cationic complexes 74 with the corresponding lithium phosphides (Equation (31)) <1985CB1193, 1985OM2097>. The polarity of the reagent can also be reversed: thus, anionic bimetallic complex (CpLi+)(CO)3MoCo(CO)4 readily reacted with chlorodiphenyl phosphine to give Mo2Co product with a carbonyl bridge between phosphorus and cobalt atoms <2000JOM(607)156>.

–78 to 0 °C

_

[Cp*M(CO)3]+BF4

+

LiPR1R2

Et2O 30 min

74

O OC R1 P M OC Cp* R2

ð31Þ

75 M = Fe, Ru R1, R2 = TMS, t-Bu

Neutral phosphines and phosphites were also applied for phosphinylation of carbonyl complexes of molybdenum <1987OM1587>, iridium <1993JCS(D)1031>, and tantalum <1987IC2556>. Reaction of Ni(COD)2 with -keto phosphonates in the presence of PPh3 affords 2-CO coordinated complexes 76 (Equation (32)) <1990OM1958>. O Ni(COD)2 +

R

P O

OMe OMe

PPh3 Et2O rt

Ph3P O Ni OMe P R Ph3P OMe O 76

R = Me (79%), Et (89%), Ph (73%), 4-ClC6H4 (65%), 4-MeC6H4 (72%)

ð32Þ

479

Functions Containing a Carbonyl Group and Two Heteroatoms

Treatment of Cp*Cl3TaSiMe3 with trialkyl phosphines or phosphites under CO atmosphere results in carbonylative phosphinylation of the tantalum complex to give adducts 77 (Figure 5) <1987IC2556, 1989JA149>, whereas carbonylation of zirconocenes bearing a phosphinefunctionalized cyclopentadiene ring affords intramolecular phosphinylation products 78 <1991OM2266, 1995OM1525>. Cp* _ O Cp*Cl3 Ta C

R3P +

R2 Zr

SiMe3

C

R = Me, Et, OMe

Ru

R1 – O

Ru C

Me

R1

92

78 1

R2

Cp*

PPh 2 +

77

C

OC

2

1

R = Me, Et; R2 = H, Me

R = Cl, Me; R = H, PPh2

Figure 5 Examples of carbonyl compounds with one phosphorus and one metal or two metal functions.

6.16.2.3

Carbonyl Derivatives with One B, As, Sb, or Bi Function, and One Metal Function

The reaction of 9-o- or 9-m-carboranecarbonyl chlorides with NaRe(CO)5 in THF at 70 C gave the corresponding Re-complexes C2H2B10-CORe(CO)5 in 58–67% yields <1987BAU1486>. The transmetallation of solvated lithium complex of arsadionate 79 using RuCl2(PPh3)3 in DME afforded the Ru complex 80 with not fully delocalized arsadionate ligand (Equation (33)) <2001JCS(D)3219>. In contrast, the analogous reactions with FeCl2 or CoCl2 gave the complexes with planar arsadionate ligands, coordinated to the metal center in a chelating 2-O,O-fashion. But

But

RuCl2(PPh3)3

O Li Li O O

DME, –78 °C

As O

But

As

But O

O Ru

Cl

73%

But

As

But

ð33Þ

PPh3 PPh3 80

79

No data on the preparation of carbonyl compounds with one Sb or Bi, and one metal function have been reported up to the early 2000s.

6.16.3

6.16.3.1

FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION (AND NO HALOGEN, CHALCOGEN, OR GROUP 5 ELEMENT FUNCTIONS) Carbonyl Derivatives with Two Silicon Functions

Two major approaches to the preparation of symmetrical bis(silyl) ketones involve C¼O bond formation in the pre-existing SiCSi fragment and are based on oxidation and hydrolysis reactions. Since the early synthesis of bis(triphenylsilyl) ketone via oxidation of the corresponding alcohol <1995COFGT(6)499>, the efforts were concentrated mostly on the preparation of the simplest representative of this class, bis(trimethylsilyl) ketone. In the oxidative approach, (Me3Si)2CO 83 (Scheme 18) was readily prepared via ozonation of bis(silylated) ylide 81 <1995COFGT(6)499, 1995LA415> or by oxidation of trimethylsilyl derivative 82 with m-chloroperbenzoic acid (MCPBA) <1995COFGT(6)499>. O3 . P(OPh)3

TMS C PPh3 TMS 81

–78 °C Toluene 30–50%

TMS O TMS 83

Scheme 18

MCPBA –78 °C CH2Cl2 45%

TMS TMS

SMe TMS 82

480

Functions Containing a Carbonyl Group and Two Heteroatoms

In the hydrolytic approach, preferred due to oxidizability of 83, -halo ethers 85, prepared by cleavage of O,S-acetal 84 with Br2 or SO2Cl2, readily hydrolyze on passing through a silica gel or alumina column to afford TMS2CO in 65–75% yields (Scheme 19) <1998ACS1141, 1998SC1415>.

TMS

TMS PhS

Br2 or SO2Cl2

TMS X

CH2Cl2

OMe

TMS OMe 85

84

Silica gel pentane ether

TMS

75–78%

83

O TMS

X = Cl (65%) X = Br (82%)

Scheme 19

Similarly, bis(silyl)bis(methylthio) ketone 86, obtained by double lithiation/silylation of bis(methylthio)methane, undergoes hydrolysis on treatment with HgOBF3 Et2O to give bis(dimethylphenylsilyl) ketone (Equation (34)) <1990CL1411>. MeS

HgO-BF3.Et2O

SMe

PhMe2Si

56%

SiMe2Ph

O PhMe2Si

ð34Þ

SiMe2Ph

86

To our knowledge, no isolable unsymmetrical bis(silyl)ketones have been synthesized up to the early 2000s, although the formation of (trimethylsilyl)(triphenylsilyl) ketone on hydrolysis of the corresponding 2,2-disilylated 1,3-dithiane was proposed on the basis of infrared spectra <1968CJC2119>.

6.16.3.2

Other Carbonyl Derivatives with Two Metalloid Functions

The first bis(germyl) ketone, Et3GeCOGeEt3, was prepared via neutral hydrolysis of the corresponding 2,2-digermyl 1,3-dithiane derivative and characterized in solution <1967JA431>. One year later, bis(triphenylgermyl) ketone was prepared in 73% yield by oxidation of the corresponding alcohol and fully characterized <1968CJC2119>. Since then, only one procedure for the preparation of these compounds has been reported: bis(trimethylgermyl) ketone 89 (M = Ge) was synthesized via germylation of thioacetal 87 followed by halogenation of 88 with SO2Cl2 and mild hydrolysis of the intermediate -chloro ether on silica gel (Scheme 20) <2000JCS(P1)2677>. Mixed (trimethylsilyl)(trimethylgermyl) ketone 89 (M = Si) was prepared similarly (Scheme 20). No data on synthesis of other carbonyl compounds with two metalloid functions have been found up to the early 2000s.

GeMe3

i. t-BuLi, THF –78 °C

OMe ii. Me 3MX

PhS 87

Me3M PhS

GeMe3 OMe

i. SO 2Cl2, CH2Cl2 0 °C, 30 min

ii. Cyclohexene THF, –78 °C 0 °C, 30 min 88 M = Si, X = Cl, 90% iii. Silica gel M = Ge, X = Br, 92% pentane

O Me3M

GeMe3 89

M = Si, 53% M = Ge, 65%

Scheme 20

6.16.3.3

Carbonyl Derivatives with One Metalloid and One Metal Function

The most general approach to the preparation of the silaacyl metal compounds is based in the insertion of carbon monoxide into the metalsilicon bond. Thus, carbonylation of silyl zirconium complexes 90 gives 2-silaacyl complexes 91 (Equation (35)) <1988CRV1059, 1988JOM(358)169, 1995COFGT(6)499>.

Functions Containing a Carbonyl Group and Two Heteroatoms R2 R1

Cp Zr SiR33 90

CO (100 psi) rt pentane or Et2O 71–90%

R2 R1

Cp Zr

481

SiR33

O 91

ð35Þ

R1 = Cp, Cp*; R2 = Cl, TMS R3 = Me, TMS

Analogous products, prepared from complexes bearing disubstituted silyl moiety, have been found to be unstable <1989OM324>. A similar procedure was applied for the preparation of 2-silaacyl complexes of Re <1995COFGT(6)499>, Ta <1989JA149, 2002OM3108>, and Fe <1992T7629>. In the latter case Fe2(CO)9 was used as a carbon monoxide source. No information on the synthesis of other carbonyl compounds with one metalloid and one metal function has been found up to the early 2000s.

6.16.4

CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

Detailed information on both homonuclear and heteronuclear polymetallic clusters with a CO bridging ligand can be found in the appropriate volumes of Comprehensive Organometallic Chemistry-II <1995COMCII> and in a series of yearly reviews titled ‘‘Organo-Transition Metal Cluster Compounds’’, published in Organometallic Chemistry e.g., <2000MI275>, so the following survey is intended to give only a brief summary of the methods used for the preparation of title compounds in the period 1994–2003. One of the most widely used approaches for the preparation of homonuclear bimetallic clusters with a CO bridging ligand is based on reductive carbonylation of the corresponding metal halides in ethylene glycol <1999JOM(580)117, 2003JOM(669)44>, or on the surface of inorganic oxides or zeolites <2003CRV3707>, or carbonylation of neutral metal complexes <2002IS210>. Enals, such as crotonaldehyde or 2-pentenal, could serve as a source of bridging CO: thus, treatment of [Cp*RuCl]4 with these enals in the presence of K2CO3 gave diruthenium complexes 92 (Figure 5) in 36–65% yields <1994OM2423>. Other dirhodium and dirhenium clusters were obtained by dimerization of the corresponding monomeric rhodium and rhenium carbonyls at room temperature or on heating <1999JOM(577)167, 2001IC2979>. Dimerization of indenyl rhenium tricarbonyl under UV irradiation was accompanied by loss of one CO ligand <1999OM1353>. Another approach, applied to the preparation of both homonuclear and heteronuclear bimetallic CO-bridged complexes, includes reaction of metalmetal bonded carbonyl compounds with external ligands, such as PPh3 <2000EJI159>, acetonitrile <2002JOM(658)117>, or alkynes <1994OM4695, 1995AJC1651, 2002OM4847>, which force one of CO ligands to change its binding mode. Similarly, the reaction of iron carbonyls with t-BuGeH3 <1994CL293> or Cp*2GaCl <2002JOM(646)247> yielded ironiron bonded complexes containing both -germylene or -gallium and -CO bridges. A similar procedure was applied to the preparation of heteronuclear clusters, such as CObridged RuPd <2002JA5628>, IrMo, IrW, IrFe <2002ICA204>, FeRe, and FeMn complexes <1998OM2945, 2000OM72>.

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Functions Containing a Carbonyl Group and Two Heteroatoms 1996USP5508400 1997BOC277 1997BSF623 1997CC1799 1997CC2311 1997HCA121 1997HCA966 1997IC4753 1997JCS(P1)2319 1997JOC3230 1997JOC3858 1997JOC4155 1997JOC5380 1997JOM(541)423 1997OM2562 1997OM5595 1997S1189 1997SC2357 1997SL1184 1997TL931 1997TL2065 1997TL4603 1997TL5335 1997WOP47626 1998ACS1141 1998CC513 1998CC2703 1998EJO183 1998EJO379 1998EUP846679 1998EUP879816 1998JCR(S)442 1998JCS(P1)2377 1998JCS(P1)3127 1998JHC261 1998JOC2424 1998JOC4802 1998JOC8515 1998JOC9252 1998JOM(563)1 1998JOM(568)241 1998JOM(568)247 1998MI129 1998MI139 1998OM131 1998OM2945 1998PHA607 1998S967 1998SC1415 1998SC3665 1998SL1325 1998T10789 1998TL179 1998TL1121 1998TL3609 1998TL3631 1998TL6267 1998TL7811 1998USP5817814 1999H(50)67

487

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488 1999H(51)2035 1999HCO473 1999IC3494 1999JCO361 1999JCR(S)710 1999JCS(P1)677 1999JHC1327 1999JOC1004 1999JOC2835 1999JOM(577)167 1999JOM(580)117 1999OL961 1999OM187 1999OM748 1999OM1353 1999OM2459 1999OM4700 1999PS(144)313 1999S453 1999S943 1999S1907 1999SL1379 1999T475 1999TL2749 1999TL2895 1999TL3235 1999TL4501 1999TL5841 1999TL6121 1999TL6545 1999TL8563 1999ZAAC1979 1999ZN(B)385 2000BAU1202 2000CAR161 2000CCA569 2000CHE837 2000EJI159 2000EJM879 2000EJO2105 2000GEP19830556 2000HAC470 2000HCO55 2000JA2966 2000JCO710 2000JCR(S)145 2000JCS(P1)2677 2000JHC1247 2000JMOC(A)11 2000JOC1549 2000JOC3239 2000JOC5216 2000JOC5887 2000JOC6368 2000JOM(598)403 2000JOM(607)156 2000M463 2000M953

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Functions Containing a Carbonyl Group and Two Heteroatoms

493

Biographical sketch

Olga Denisko was born in Krasnoyarsk, Russia and studied at Moscow State University, Russia, where she obtained her Ph.D. in 1993 under the direction of Professor N. S. Zefirov. During 1994–1996, she worked as a Postdoctoral Research Fellow in the Center for Heterocyclic Compounds, University of Florida, FL under supervision of Professor A. R. Katritzky, after which she returned to Russia and was employed as a Chemist in the Central Laboratory of ‘‘Krasfarma’’ Pharmaceuticals (Krasnoyarsk, Russia). In 1998, she returned to the University of Florida as Postdoctoral Research Fellow/Group Leader. After working there for another two years, she was employed as a Senior Research Chemist by Alchem Laboratories (Alachua, FL). In June 2002, she took up her present position as Assistant Scientific Information Analyst at the Chemical Abstracts Service, Columbus, OH. Her scientific research interests include various aspects of heterocyclic organic chemistry and chemistry of organosulfur compounds.

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 453–493

6.17 Functions Containing a Thiocarbonyl Group and at Least One Halogen; Also at Least One Chalcogen and No Halogen E. KLEINPETER University of Potsdam, Potsdam, Germany 6.17.1 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 6.17.1.1 Thiocarbonyl Halides Containing Two Halogens 6.17.1.2 Sulfoxides of Thiocarbonyl Halides (Sulfines) 6.17.1.3 Thiocarbonyl Halides Containing One Halogen and One Other Heteroatom 6.17.1.3.1 Halogenothioformates, ROC(Hal)¼S 6.17.1.3.2 Chlorothioformates, ROC(Cl)¼S 6.17.1.3.3 Halogenodithioformates, RSC(Hal)¼S 6.17.1.3.4 Chlorodithioformates, RSC(Cl)¼S 6.17.1.3.5 Thiocarbamoyl halides, R2NC(Hal)¼S 6.17.1.3.6 Thiocarbamoyl chlorides, R2NC(Cl)¼S 6.17.2 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION (AND NO HALOGEN) 6.17.2.1 Thionocarbonates (O,O-Diesters of Thiocarbonic Acid) 6.17.2.1.1 From thiophosgene 6.17.2.1.2 From chlorothionoformates 6.17.2.1.3 From thiocarbonyldiimidazole 6.17.2.2 Dithiocarbonates (Esters of Dithiocarbonic Acid) 6.17.2.2.1 Salts of O-alkyl esters of dithiocarbonic acid (xanthates) and bisalkoxythiocarbonyl disulfides 6.17.2.2.2 O,S-Diesters of dithiocarbonic acid 6.17.2.2.3 Sulfoxides of O,S-diesters of dithiocarbonic acid (sulfines) 6.17.2.3 Thiocarbamates (Esters of Thiocarbamic Acid) 6.17.2.3.1 From O-alkyl or O-aryl chloroformates and amines 6.17.2.3.2 From N,N-dialkylthiocarbamoylchlorides and alcohols or phenols 6.17.2.3.3 From N,N 0 -thiocarbonyl diimidazole and alcohols 6.17.2.3.4 From thiophosgene and 1,2-amino alcohols 6.17.2.3.5 From CS2 and 1,2-amino alcohols 6.17.2.3.6 From isothiocyanates and alcohols 6.17.2.3.7 N-acyl-1,3-oxazolidine-2-thiones as auxiliary agents 6.17.2.3.8 By thermal conversion of 2-allyl thiobenzothiazoles 6.17.2.3.9 Other methods 6.17.2.4 Dithiocarbamates (Esters of Dithiocarbamic Acid) 6.17.2.4.1 Alkali metal salts of N,N 0 -disubstituted dithiocarbamic acid (dithiocarbamates)

495

495 495 497 498 498 498 499 500 501 501 502 502 503 504 509 510 510 511 519 520 520 521 521 521 522 523 528 528 528 530 530

496

Functions Containing a Thiocarbonyl Group and at Least One Halogen 530 534 534 534 534

6.17.2.4.2 Esters of dithiocarbamic acids 6.17.2.4.3 Bis-[thiocarbamoyl](thiuram)disulfides 6.17.2.5 Trithiocarbonates (Esters of Trithiocarbonic Acid) 6.17.2.5.1 Salts of monoesters of trithiocarbonic acid 6.17.2.5.2 Diesters of trithiocarbonic acid

6.17.1 6.17.1.1

FUNCTIONS CONTAINING AT LEAST ONE HALOGEN Thiocarbonyl Halides Containing Two Halogens

All four thiocarbonyl halides with identical halogens are known and were synthesized prior to 1995 (see Table 1 for characteristic properties). Thiocarbonyl diiodide is the only one that has not been isolated, due to its labile nature, thus far and its identification has been based on IR. These compounds tend to polymerize easily <1974MI25> and their stability is dependent on both the character of the C¼S double bond and the donor activity of the attendant halogens <1976CB3432>. As acid halides, they react readily with alcohols, amines, etc., to yield the corresponding carbonic acid derivatives in high yields. Some thiocarbonyl halides with dissimilar halogens have also been synthesized and are included in Table 1. Caution! Thiocarbonyl halides must be handled with great care as they are highly toxic and it is imperative that exposure by ingestion, inhalation, or direct absorption through the skin be avoided. As a minimum precaution, all operations should be conducted in a well-ventilated fume hood. Table 1

Thiocarbonyl halides—properties and references for the most useful syntheses

Compound F2C¼S Cl2C¼S Br2C¼S I2C¼S FClC¼S FBrC¼S ClBrC¼S

Properties

References

Colorless gas, b.p. 54 C Red liquid, b.p. 73.5 C Orange-red liquid, b.p. 142–144 C Not yet isolated; identification by IR, C¼S = 1062 cm1 and CI = 602 cm1 Yellow liquid, b.p. 7 C Yellow liquid, b.p. 4–8 C (100 mmHg) Red liquid, b.p. 47 C (80 mmHg)

<1965JOC1375> <1974S26> <1974IC1778> <1968ZAAC180> <1959ZOB3792> <1981CB829> <1981CB829>

The syntheses of the thiocarbonyl halides have been extensively reviewed in COFGT (1995), and the references for the most useful syntheses are collected in Table 1. The most convenient synthesis of thiophosgene (Cl2C¼S) is by the reduction of perchloromethylsulfenylchloride (Cl3CSCl) with H2S at 110–114 C <1974S26>; other reducing agents have also been used. Alternatively, trichloromethyl thiol (Cl3CSH) can be reduced with SO2 in the presence of KI and S2Cl2 <1983HOU(E4)408> to provide thiophosgene (Scheme 1).

Cl3C SCl

Cl3C SCl

Reduction H2S, 114 °C 96%

Reduction (SO2, KI, S2Cl2) 97%

Cl S C Cl

Cl S C Cl

Scheme 1

The other three symmetric thiocarbonyl halides are, in fact, available by the direct derivatization of thiophosgene. However, the most useful syntheses are as follows: F2C¼S by a three-step procedure via dimerized thiophosgene which is fluorinated using SbF3 and the resulting 2,2,4,4tetrafluoro-1,3-dithietane decomposed by pyrolysis <1965JOC1375> (Scheme 2).

497

Functions Containing a Thiocarbonyl Group and at Least One Halogen Cl

Cl

S

Cl

Cl

Cl

S

F

SbF3

2S C Cl

F

S S

F

(475 –500 °C)

F 2S C

90%

F

F

Scheme 2

Br2C¼S from F2C¼S in 97% yield by reaction with anhydrous HBr <1974IC1778> and I2C¼S from carbon monosulfide by reaction with I2 <1968ZAAC180>. The three thiocarbonyl halides with dissimilar halogens reported thus far have been obtained as follows: FClC¼S from FCl2CSCl in 87% yield by reduction using Sn/HClconc <1959ZOB3792>; FBrC¼S from FClC¼S by halogen exchange using BBr3 at 65 C <1981CB829> and ClBrC¼S from thiophosgene by halogen exchange using BBr3 <1981CB829>. The high-temperature thiation of thiophosgene with elemental sulfur has been reinvestigated by Christensen and Senning <2000SUL23>. The reaction was shown to lead to a multitude of primary, secondary, and tertiary products which are probably the result of the cycloaddition of thiophosgene S-sulfide Cl2C¼S¼S and/or thiophosgene S-disulfide Cl2C¼S¼S¼S followed by sulfur extrusion and various dechlorination/chlorination steps.

6.17.1.2

Sulfoxides of Thiocarbonyl Halides (Sulfines)

Four sulfoxides of thiocarbonyl halides are known thus far and all were synthesized prior to 1995 (see Table 2 for characteristic properties and the most useful syntheses). They are very labile compounds and can be detected only under extreme conditions except for thiophosgene-S-oxide (dichlorosulfine). The synthesis, structural analysis, and chemistry of dichlorosulfine have been reviewed <1992SUL275>. In its simplest preparation, it is obtained from 2,2,4,4-tetrachloro-1, 3-dithietane by oxidation using trifluoroperoxyacetic acid at 40 C and the resulting 1,3-dioxide quantitatively cleaved by vacuum pyrolysis at 480 C and 0.5 mmHg <1983CB1623> (Scheme 3).

Table 2 Sulfoxides of thiocarbonyl halides—properties and references for the most useful syntheses Compound

Properties

References

Decomposes at 100 C; detected by MS Yellow liquid, b.p. 34–36 C (25 mmHg) Reddish liquid; identified by IR in an argon matrix Decomposes at 100 C; detected by MS

F2C¼SO Cl2C¼SO Br2C¼SO FClC¼SO

Cl Cl

S S

Cl Cl

CF3CO3H, CH2Cl2

Cl

40 °C

Cl

O S S O

Cl Cl

∆ 51%

<1988JFC329> <1992SUL275> <1985CB1415> <1988JFC329>

Cl O S C Cl

Scheme 3

Dichlorosulfine can also be obtained from thiophosgene directly (by oxidation using peroxybenzoic acid <1969TL4461>), from Cl3CSCl (by hydrolysis <1969CC878>) and from allyl trichloromethyl sulfoxide Cl3CSOCH2CH¼CH2 (by pyrolysis at 300–400 C <1986CB269>). It is much more difficult to synthesize than the other three sulfoxides reported thus far (all were obtained prior to 1995), since they decompose spontaneously at low temperatures. None have been isolated, but some have been identified on the basis of IR and MS analyses (cf. COFGT (1995)).

498

Functions Containing a Thiocarbonyl Group and at Least One Halogen

6.17.1.3

Thiocarbonyl Halides Containing One Halogen and One Other Heteroatom

6.17.1.3.1

Halogenothioformates, ROC(Hal)¼S

The syntheses of both fluoro- and chlorothioformates have been reported. Thiocarbonyl chloride fluoride (ClFC¼S) reacts readily with alcohols in the absence of solvent leading selectively to the alkyl fluorothioformates ROC(F)¼S (R = alkyl) <1959ZOB3792>. In particular, the aryl chlorothioformates (PhOC(Cl)¼S) have been employed extensively as starting reagents for the syntheses of the corresponding di- and trithiocarbonates and thiocarbamates (vide infra). The syntheses of bromo- and iodothioformates have not been reported as of early 2004.

6.17.1.3.2

Chlorothioformates, ROC(Cl)¼S

Phenols and its analogs react readily with thiophosgene in (chloro)hydrocarbon solvents together with base to provide the corresponding aryl chlorothioformates in excellent yields, e.g., <1985SUL61> (Equation (1)). Cl

Cl

Cl Cl

Cl

OH

+

S C Cl

Cl

NaOH –HCl 99%

Cl

Cl Cl S

Cl

O

ð1Þ Cl

Cl

Colorless solid; m.p. 108–112 °C

Phenyl chlorothioformate PhOC(Cl)¼S, a yellow liquid boiling at 91 C (10 mmHg), can be synthesized easily employing this procedure with yields in excess of 95% (cf. COFGT (1995), <1983HOU(E4)408>). This compound has often been used for the syntheses of the corresponding di- and trithiocarbonates and thiocarbamates (vide infra) and has proven to be very useful for introducing the thiocarbonyl functionality into organic compounds (vide infra). The in situ preparation of thiophosgene for the generation of phenyl chlorothioformate has been accomplished by the chlorination of CS2, by the reduction of CCl3CSCl, or by the reduction of CCl3SH using SO2 (COFGT (1995)). The corresponding alkyl chlorothioformates (e.g., ethyl chlorothioformate, a yellow liquid, b.p. 53–55 C (40 mmHg)) can be synthesized by three different approaches. (i) From thiophosgene, by the reaction with potassium alkoxide in the corresponding alcohol at low temperatures; yields are in excess of 90%, cf. Table 3 <1986S760>. (ii) From thiophosgene, by the reaction with alkoxytrimethylsilanes; although not requiring basic conditions, the yields, however, are less than 35% <1986S760>. (iii) By the chlorination of bis(alkoxythiocarbonyl)disulfides with Cl2 or SOCl2 <1983JOC4750>. However, the yields are low, under 70%, and the reaction products are difficult to purify. In addition, it is strongly advised that only very pure reagents be used for the preparation <1986S760> (Scheme 4). Table 3

Chlorothioformates—properties and yields <1986S760> Yield (%)

Compound EtOC(Cl)¼S n-BuOC(Cl)¼S

81 85

n-PrOC(Cl)¼S i-PrOC(Cl)¼S i-BuOC(Cl)¼S

91 88b 89

a

<1984ZAAC136>.

b

Properties b.p. 46 C (33 mmHg); n18 D 1.4879, C¼S b.p. 62 C (12 mmHg); n18 D 1.4815, C¼S spectroscopic data provideda b.p. 42 C (12 mmHg); n18 D 1.4885, C¼S b.p. 34 C (10 mmHg); C¼S 1280 cm1 b.p. 54 C (10 mmHg); n18 D 1.4776, C¼S

1270 cm1 1260 cm1; 1260 cm1 1278 cm1

In THF.

In the development of non-nucleoside reverse transcriptase inhibitors and as part of a total synthesis of such, Hahn and co-workers <2000MI66> synthesized i-propyl chlorothioformate (i-PrOC(Cl)¼S) from i-propanol and thiophosgene (in DMF/Et3N). The i-propyl chlorothioformate

499

Functions Containing a Thiocarbonyl Group and at Least One Halogen

(i) AlkOK

+

Cl

AlkOH –65 °C

S C Cl

(ii) AlkO SiMe3

S C Cl

(iii) AlkO C

S S C OAlk

C S AlkO

Cl

Cl +

Cl

80 °C

Cl2 or SOCl 2

C S AlkO

Cl C S AlkO

S S

Scheme 4

was not isolated but treated with a number of substituted anilines to provide the corresponding thiocarbamates (i-PrOC(S)NHAryl) in low yield <2000MI66>.

6.17.1.3.3

Halogenodithioformates, RSC(Hal)¼S

A number of halogenodithioformates RSC(Hal)¼S have been prepared, and are presented together with their most useful syntheses in Table 4. The most effective route for the synthesis of F3CC(F)¼S is by the reaction of FClC¼S with Hg(SCF3)2 at room temperature <1972CB820> (yield, 96%). In a similar fashion, C6F5SC(Cl)¼S was obtained from Hg(SC6F5)2 and thiophosgene <1984T4963> and F3CSeC(F)¼S from Hg(SeCF3)2 and FClC¼S at 78 C <1976ZAAC114>. A few halogenodithioformates have also been obtained by the reaction between thiols (RSH) and the corresponding thiocarbonyldihalogenides (Hal2C¼S) (COFGT (1995)): AlkSC(F)¼S in the absence of solvent <1959ZOB3792>; AlkSC(Cl)¼S in dry CS2 at room temperature in 55–70% yield <1984ZAAC136>; and AlkSC(Br)¼S in ether at room temperature under argon <1984ZAAC61>. Table 4 Halogenodithioformates—properties and references for the most useful syntheses Compound

Properties

CF3SC(F)¼S CF3SC(Cl)¼S CCl3SC(Cl)¼S C2Cl5SC(Cl)¼S EtSC(Br)¼S

n-PrSC(Br)¼S n-PrSC(Cl)¼S i-PrSC(Cl)¼S n-BuSC(Cl)¼S CF3SC(Br)¼S CF3SeC(F)¼S CF3SeC(Cl)¼S CF3SeC(Br)¼S EtSeC(Cl)¼S i-PrSeC(Cl)¼S CF3SeC(Cl)¼SO CF3SeC(Br)¼SO

Yellow liquid, b.p. 43 C Orange oil, b.p. 98–100 C (14 mmHg) Orange oil, b.p. 78–80 C (0.04 mmHg) Orange oil, b.p. 108–109 C (0.03 mmHg) Deep red liquid, storage at 20 C under argon required; spectroscopic data provided Deep red liquid, storage at 20 C under argon required; spectroscopic data provided Yellow liquid, b.p. 57 C (21 mmHg); nrtD 1.5795, spectroscopic data provided Yellow liquid, b.p. 83–85 C (21 mmHg); nrtD 1.5699, spectroscopic data provided Yellow liquid, b.p. 103–104 C (21 mmHg); nrtD 1.5696, spectroscopic data provided Red liquid, b.p. 57–58 C; spectroscopic data provided b.p. 57–58 C; spectroscopic data provided Yellow viscous oil Liquid, b.p. 54 C (50 mmHg); spectroscopic data provided Red, viscous oil, b.p. 88 C (23 mmHg); spectroscopic data provided Red, viscous oil, b.p. 102–104 C (23 mmHg); spectroscopic data provided Yellow liquid, b.p. 47 C (10 mmHg) Yellow liquid, b.p. 60 C (10 mmHg)

References <1972CB820> <1984JOC3854> <1986ACS(B)609> <1986ACS(B)609> <1984ZAAC61> <1984ZAAC61> <1984ZAAC136> <1984ZAAC136> <1984ZAAC136> <1976CB3432> <1976ZAAC114> <1976ZAAC114> <1986ZN(B)413> <1984ZAAC61> <1984ZAAC61> <1986ZN(B)413> <1986ZN(B)413>

500

Functions Containing a Thiocarbonyl Group and at Least One Halogen

The analogous selenoesters (AlkSeC(Cl)¼S) have also been produced from the reaction of alkyl selenols <1976ZAAC114>. In addition, F3CSeC(Cl)¼S has been synthesized from F3CSeC(F)¼S in 97% yield by halogen exchange using BCl3 <1976ZAAC114> and F3CSeC(Br)¼S from F3CSeC(F)¼S after UV irradiation for 4 h and halogen exchange with BBr3 at 40 C in 74% yield <1986ZN(B)413>. The sulfines were produced by oxidation of the halogenodithioformates using m-chloroperoxybenzoic acid (MCPBA) <1986ZN(B)413>.

6.17.1.3.4

Chlorodithioformates, RSC(Cl)¼S

There are five main routes available for the synthesis of the chlorodithioformates.

(i) From thiols For example, alkyl chlorodithioformates (cf. Table 4) can be easily synthesized from the corresponding alkyl thiols and thiophosgene in good yields at room temperature <1984ZAAC136>, and similarly from the aryl thiols <1985SUL61>.

(ii) By the insertion of carbon monosulfide This method has been employed for the syntheses of a number of alkyl and aryl chlorodithioformates <1984JOC3854, 1984JA263, 1986SUL203, 1986ACS(B)609, 1991SUL143, 1998SUL53>. (It should be noted that the continuous production of CS requires special care and equipment <1986ACS(B)609>.)

(iii) From sulfochlorides For example, methyl chlorodithioformate MeSC(Cl)¼S can be obtained from (MeS)2CClSCl by hydrolysis (using water, aqueous KI, or MeSH), from MeSC(Cl)2SSMe (again by hydrolysis using water, aqueous KI, or MeSH), or from MeSC(Cl)2SCl (using MeSH) <1992SUL275>.

(iv) From alkali metal dichlorodithioformates Alkali metal dichlorodithioformates MSC(Cl)¼S, prepared from alkali chlorides/NaOH and CS2 <1983ZAAC7>, have been alkylated, for example, using ethyl iodide to yield ethyl chlorodithioformate EtOC(Cl)¼S <1983ZAAC7>.

(v) From arenediazonium salts and CS2 Aryl chlorodithioformates have been produced by the reaction of arene diazonium chlorides with CS2 under Sandmeyer conditions (Cupowder or CuCl at room temperature) (Scheme 5). Cl +

(i)

C S

CS2 CuCl

–

N N Cl

S

X

X Cl Cl

(ii)

SH + S C X

Cl

C S

NaOH, CHCl3

S

–HCl

Scheme 5

X

501

Functions Containing a Thiocarbonyl Group and at Least One Halogen 6.17.1.3.5

Thiocarbamoyl halides, R2NC(Hal)¼S

In addition to a number of thiocarbamoyl chlorides (R2NC(Cl)¼S), some fluoride <1970LA195, 1970LA158, 1975LA1025> and bromide analogs <1970LA195, 1972LA145> have also been synthesized. Only the N,N-disubstituted derivatives of thiocarbamoyl halides are sufficiently stable to enable isolation; the N-monosubstituted thiocarbamoyl halides decompose spontaneously after formation to the corresponding isothiocyanates with the evolution of HCl. Fluorothiocarbamates have been obtained directly from the reaction between thiocarbonyl chloride fluoride and secondary amines. A few other patented methods have been reported, e.g., N,N-dimethylthiocarbamoyl fluoride was obtained by treating F2C¼CFR (R = H, Cl, CF3) with tetramethylthiouramide sulfide at 130–135 C (COFGT (1995)). The thiocarbamoyl bromides R2NC(Br)¼S known thus far have been produced by the reaction between bromine and the thiocarbamoyl chlorides R2NC(Cl)¼S.

6.17.1.3.6

Thiocarbamoyl chlorides, R2NC(Cl)¼S

Thiocarbamoyl chlorides are sufficiently stable to permit isolation; selected examples are listed in Table 5. Dimethyl and diethylthiocarbamoyl chloride and other N,N-disubstituted analogs continue to be very popular as reagents for introducing sulfur into organic compounds. Dimethylthiocarbamoyl chloride has been investigated using gas-phase electron diffraction <2003JPC(A)4697>; the molecule exists as a single near-planar conformer in the gas phase.

Table 5

Thiocarbamoyl chlorides—properties and references for the most useful syntheses

Compound Me2NC(Cl)¼S Et2NC(Cl)¼S Et2NC(Cl)¼S O(CH2CH2)2NC(Cl)¼S Ar,a MeNC(Cl)¼S Ar,b MeNC(Cl)¼S Ar,c MeNC(Cl)¼S Me2NN(Me)C(Cl)¼S Me2NN(R)C(Cl)¼Sd R2NN(Me)C(Cl)¼Se R2NN(Me)C(Cl)¼Sf a d

Properties; method; yield

References

m.p. 43 C; chlorination using SO2Cl2; 97% b.p. 100 C (21 mmHg); Me2NH, S¼CCl2; 46% b.p. 70 C (13 mmHg); chlorination using SO2Cl2; 97% b.p. 96 C (17 mmHg); O(CH2CH2)2NH, S¼CCl2; 83% m.p. 44–45 C; chlorination using CSCl2; 45% m.p. 79–80 C; chlorination using CSCl2; 80% m.p. 108–109 C; chlorination using CSCl2; 80% m.p. 64–65 C; method (i); 69% m.p. 30 C; method (i); 29% m.p. 93 C; method (i); 54% m.p. 41–42 C; method (i); 23%

<1990SC2769> <1983HOU(E4)408> <1988ZOB1468> <1988ZOB1468> <1970LA158> <1970LA158> <1970LA158> <1972CB2854> <1991AP(324)917> <1991AP(324)917> <1991AP(324)917>

2-i-Propyl-1,3,4-thiadiazolo-5-onyl. b 2-Phenyl-1,3,4-thiadiazolo-5-onyl. R = cyclohexyl. e NR2 = morpholino. f NR2 = piperidino.

c

2-Cyclohexyl-1,3,4-thiadiazolo-5-onyl.

There are three main synthetic routes.

(i) From thiophosgene and secondary amines or their synthetic equivalents Thiophosgene reacts readily with secondary amines in inert solvents to yield thiocarbamoyl chlorides. The HCl formed in the reaction can be taken up by a further equivalent of the secondary amine without formation of the corresponding thiourea derivatives <1970LA158, 1975LA1025> (cf. Table 5). Alternatively, thiophosgene can be reacted with N-trimethylsilylimide, triphenylphosphinium chloride, or N-trimethylsilyl-1,3-dimethyl-2-imidazoline <1987UKZ395> to effect the same result <1997ZN(B)1055> (Scheme 6). If trialkyl-substituted hydrazines are used instead of secondary amines, the corresponding thiocarbazic acid chlorides (R2NN(R)C(Cl)¼S) result (cf. Table 5) <1972CB2854, 1991AP(324)917>. Thiocarbazic acid chlorides are very useful reagents for the thiocarbazoylation of thiazine-2-ones and thiazolidin-2-ones <1991LA405> (Equation (2)).

502

Functions Containing a Thiocarbonyl Group and at Least One Halogen

Me N N SiMe3

N Me

+

–

Ph3P NH2 Cl

S

S CCl2

Ph3P N SiMe3

Ph3P N C

Cl

Me N

S CCl2

S N C Cl

N Me

S CCl2

S Ph3P N C

Cl

Scheme 6

Cl R2N NHR

+

S

CH2Cl2

S C

low temp.

Cl

R2N NR C

ð2Þ

Cl

69%

R = Me

(ii) From tetraalkyl thiuramide disulfides Thiocarbamoyl chlorides have also been synthesized by chlorination of the corresponding tetraalkyl thiuramide disulfides. In addition to elemental chlorine, S2Cl2 has also been employed as a chlorinating agent <1983JOC1449, 1988ZOB1468, 1990SC2769>. The yields are in excess of 70% in refluxing benzene or carbon tetrachloride (Equation (3)). S R2N C

S

S S

C NR2

Cl2 CCl4 80%

S 2R2N C

Cl

ð3Þ

R = Me

(iii) From thioformamides The third method in general use is by the chlorination of thioformamides (obtainable from the corresponding formamides by application of Lawesson’s reagent) using chlorine, SCl2, or SO2Cl2 as the chlorinating agent. Both aliphatic and aromatic thiocarbamoyl chlorides can be obtained employing this method (Scheme 7).

Me Ar N CH O

Lawesson’s reagent

Me

SO2Cl2/Et3N

CH S

CCl 4 Ar = Ph 78%

Ar N

Me Ar

N C S Cl

Scheme 7

6.17.2

6.17.2.1

FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION (AND NO HALOGEN) Thionocarbonates (O,O-Diesters of Thiocarbonic Acid)

As thiocarbonylating agents for the esterification of alcohols and phenols, in addition to thiophosgene, alkyl- as well as aryl chlorothionoformates and thiocarbonyldiimidazole have been

Functions Containing a Thiocarbonyl Group and at Least One Halogen

503

employed, the latter under especially mild reaction conditions. The yields obtained are generally good. Table 6 lists the properties and starting materials for the syntheses of selected thionocarbonates. The main synthetic routes are given as follows.

Table 6

O,O-Diesters of thiocarbonic acid—starting material and properties O,O-Diesters of thiocarbonic acid

Starting material PMB

Boc N OH

Properties

Yield (%)

References

[]D +43.7 () []20 D 7.3 (+) []20 +5 D

84 69 77

<2002JOC6896>

R = Boc, colorless oil; []20 D +10.2 ; NMR

71

<1997LA757>

R = Bzl, colorless oil; []20 D +37.2 ; NMR

89

Pale yellow oil; []20 D 6.7

82

<1996H745>

m.p. 106–108 C

87

<1995JOC5170>

<1999TA3483>

OH

OH Si OH

HO HO

COOEt N R

Br PvO

Cl O

OH OH

OH HO O

6.17.2.1.1

OMe

From thiophosgene

Both monohydroxy alcohols and cis-diols react readily with thiophosgene to form the corresponding O,O-diesters (cf., e.g., Scheme 8 <2002CAR397, 2000IJ241>). This method especially (conditions: Cl2C¼S, CH2Cl2, dimethylaminopyridine, 0 C to 10 C) has been employed for the diastereoselective synthesis of the O,O-diesters of a number of diols with complete retention of the configuration(s) present in the diols. Very often, the thionocarbonate group serves as an intermediate or protective group which can be easily converted into the corresponding alkene by Corey–Winter elimination <1999HCA1610, 1997TA2967>. Often, thionocarbonates (but also other derivatives of thiocarbonic acid) have been produced as intermediates in the course of the deoxygenation of alcohols. For the deoxygenation

504

Functions Containing a Thiocarbonyl Group and at Least One Halogen

BnO O OH

Me O Me

O

CSCl2 PhOH Pyr CH2Cl2

S C BnO O O

OPh Me

BnO O Me O

O Me

O

Me

O

S HO

O

OH

O

CSCl2 DMPD CH2Cl2 –10 °C 66–71%

Scheme 8

of C(2) of a protected L-arabinose, the secondary hydroxyl was reacted with several different reagents to obtain various radical precursors, which were further treated under normal free radical deoxygenation conditions to yield the deoxygenated product <2002CAR397> (Scheme 9).

BnO O OH

Me

Reagent

BnO O

BnO O OR

O

O

O O

Me

Me

Me

O

Me

O

Me

R = C(S)SMe, C(S)NHPh, C(S)Im2 , C(S)OPh

Scheme 9

The best yields were obtained for the S-methylxanthogenate, though the high flammability of CS2 limits the use of this method to small-scale syntheses. The other reagents tested (PhN¼C¼S, C(S)Im2 and PhOC(S)Cl) did not yield promising results, either because they were insuffficiently reactive or the reagents utilized were too expensive. The most efficient deoxygenation was achieved by preparing the phenoxythiocarbonylester (R¼C(S)OPh) in situ (phenol/pyridine in anhydrous CH2Cl2 was treated with thiophosgene) which was then directly reacted with the secondary alcohol <2002CAR397>.

6.17.2.1.2

From chlorothionoformates

Addition of phenyl chlorothionoformate [PhOC(S)Cl] to solutions of secondary alcohols (e.g., in dry acetonitrile) led to the isolation of the corresponding thionocarbonates in good yields which were readily reduced to the dehydrogenation product. This method has widely been employed in different types of compounds (cf. Table 7). In a number of cases, the thionocarbonates were not isolated <2002JOC6896, 2001JOC8935, 2001BMCL1609, 1998JA13003, 1998AG(E)965, 1998JOC44, 1995JOC7149, 1995LA1533> (Equation (4)).

Table 7 Compound

Synthesis and properties of phenylthiocarbonates synthesized from the corresponding secondary alcohol Synthesis

Properties; yield

References

OMe OR' OR' RO

OR' O S

PhOC(S)Cl/pyridine CH2Cl2 20 C

Colorless foam, 1 H, 13C, IR, MS; 94%

<2002CEJ1856>

N,N-Dimethylaminopyridine/ (DMAP)/acetonitrile/ PhOC(S)Cl rt

Yellow foam, 1 H, 13C, MS; 58%

<2000CEJ2409>

Pyridine/CH2Cl2 DMAP/PhOC(S)Cl; rt

Light yellow foam, 1 H, 13C; 86%

<1999HCA1005>

OPh

N CH N(CH3)2 NH O Si O Si

O

O

N

O

O O

S O

N(i-Bu)2 N N

N

O N O Si O Si O O

N

S O

ODPC

Table 7 (continued) Compound

Synthesis

Properties; yield

References

CO2Me

S O

OPh S

OH

H H

O

H O H O

O

H

H

O

Pyridine/DMAP acetonitrile PhOC(S)Cl rt

1:1 mixture of diastereomers []29 D +25.5 C (CHCl3) IR, 1H, 13C; 66%

<1999JOC9416>

Acetonitrile (Ar) PhOC(S)Cl rt

Colorless foam UV, 1H, MS; 62/82%

<1999JCS(P2)849>

Pyridine/CH2Cl2 0 C PhOC(S)Cl/pyridine

Colorless viscous oil 1 H, 13C; 75%

<1999EJO875>

R

HO O RO O

<2000T3425>

OR

OAc

O

Red oil/E/Z isomers TR, 1H, 13C, MS; 82%

OR

OH H

S

Pyridine/THF/DMAP/ PhOC(S)Cl; 0 C

S

RO S

OR O OPh

OPh

O

O

S

S H

O

H

OH

H OR

O H

H

OR

H

O OR

O H

H

OR

O

Si

O

Base

O O

S

R O Si

O

PhOC(S)Cl DMAP/acetonitrile (Ar)

m.p. 73–80 C IR, 1H 77%

<1997JOC8309>

PhOC(S)Cl/pyridine/ DMAP/CH2Cl2

Colorless oil 1 H, IR, MS 85%

<1996T4257>

PhOC(S)Cl DMAP, acetonitrile

Colorless oil 1 H, MS; 27%

<1996MI97>

Pyridine (Ar) acetonitrile DMAP, 0 C

Yellowish oil 1 H, 13C, MS (FAB) 88%

<2000T1475>

H

O C S OPh

H O R

H N

O RO O O

S

O

N

C PhO RO

O HN N O PhO C O S

O Si(i-Pr)2 O O Si (i-Pr)2

508

Functions Containing a Thiocarbonyl Group and at Least One Halogen R

R

R'

R' CH O C S PhO

+ PhO C(S)Cl

CH OH

RCH2R'

ð4Þ

The HOC(2) group of the ortho-ester of myo-inositol acts as an H-bond donor in a bifurcated, intramolecular H-bond, and the HOC(4) and HOC(6) groups form a strong intramolecular H-bond with one of them acting as a donor and the other as an acceptor. This leads to markedly different nucleophilicities for the three HO groups; the C(4) hydroxy group can be selectively monothiocarbonylated by 4-O-tolylthiochloroformate. The regioselectivity of this acylation is evident from the lack of symmetry expressed in the 1H NMR spectrum of the resulting thionocarbonate <1998HCA688> (Equation (5)). Bu

Bu H O O O

O O

O O C(S)Cl

CH3

+

HO

HO

O H O H

O

ð5Þ O

C S

CH3

In the course of the -deoxygenation of ()-detoxinine, a ()-hydroxylactam was converted to the corresponding thionocarbonate in 85% yield, again employing phenyl chlorothionoformate, which also permitted a convenient determination of the enantiomeric purity (>99% ee by chiral HPLC) <1997JOC1668> (Equation (6)). O

O N

HO

PhO

H

i-Pr Si i-Pr

O

C(S)Cl

N

S C OPh H i-Pr Si i-Pr

O

ð6Þ O

Thionocarbonates have been successfully used in radical-initiated deoxygenation reactions in carbohydrate derivatives. Phenyl thiocarbonates are well suited because of the high reactivity of PhOC(S)Cl with secondary alcohols and because the resulting thionocarbonates undergo clean photolytic cleavage. Photolysis yields the allylic product stereochemically pure (71–78%) <1995ACS217> (Scheme 10).

O

O

B

i-Pr2Si O

OH

O

Si i-Pr2

UV

CH

CH2

O

O

O

i -Pr2Si O Si i -Pr2

Scheme 10

O

B

i -Pr2Si

DMAP CH2Cl2, rt

O Bn3Sn2CH2

O

PhO–C(S)Cl

B

O Si i -Pr2

O C O PhO

509

Functions Containing a Thiocarbonyl Group and at Least One Halogen 6.17.2.1.3

From thiocarbonyldiimidazole

Thiocarbonyldiimidazole reacts with alcohols and 1,2-diols forming acyclic or cyclic thiocarbonates, respectively (COFGT (1995)). Examples of the formation of a thionocarbonate (which was reduced with tributyltin hydride and AIBN in an ensuing step) from thiocarbonyldiimidazole and a secondary alcohol <2000T4667> or a 1,2-diol <2002CL1879> are the following (Scheme 11).

S CH3O

CH3O

OH

N

N

N

N

O

S

CH3

O

O

CH3

O

OCH3

N

Then MeOH 36%

N

O

/DMF

N H

N H

S N OH OH O

O

N

N

N O

DMF 95%

R

O

O

S

O R

Scheme 11

The same procedure for the syntheses of various thionocarbonates has been employed for other 1,2-diols <2002TL2801, 2002T2339, 2001T3567, 2001OL2141, 1999BMCL2625, 1999OM2061>. Additionally, cyclic thionocarbonates can be used for protecting glycols <1997JOC4159> and possess similar properties as carbonates, i.e., they are stable in acidic media but are converted to the starting diols in basic media by hydrolysis. Phenyl 2,3-O-thionocarbonyl-1-thio--L-rhamnopyranosides (readily prepared from 2,3-diols in the presence of thiocarbonyldiimidazole, yield 81%) by the action of methyltrifluoromethanesulfonate (MeOTf) afforded the 3-O-(methylthio)carbonyl-2-S-phenyl-2,6-dideoxy--L-glucopyranosides (ready precursors of the corresponding 2-deoxy--glycosides) in high yields (Scheme 12).

S SPh

SPh O

RO HO

OH

N

N

N

N

O

RO O THF S

O

MeOTf ROH

O

RO

OR SPh

O S MeS

Scheme 12

More specialized methods for the syntheses of thionocarbonates have been reviewed elsewhere <1983HOU(E4)408> (COFGT (1995)).

510 6.17.2.2

Functions Containing a Thiocarbonyl Group and at Least One Halogen Dithiocarbonates (Esters of Dithiocarbonic Acid)

Dithiocarbonic acid [S¼C(OH)SH] cannot be isolated as it decomposes spontaneously. The mono-O-esters also decompose readily, especially in acidic media, but are sufficiently stable to enable isolation at low temperatures and to be analytically characterized. The salts (xanthates) are stable but the synthetic efforts within the review period mainly concentrated on the chemistry of the corresponding diesters <1983HOU(E4)408> (COFGT (1995)).

6.17.2.2.1

Salts of O-alkyl esters of dithiocarbonic acid (xanthates) and bisalkoxythiocarbonyl disulfides

Usually the sodium or potassium salts (e.g., ROC(S)SK+) were synthesized. These xanthates were prepared from the corresponding alcohols ROH, CS2, and KOH using the same alcohol as solvent if possible. Practically all alcohols, including starch and cellulose, react <1983HOU(E4)408> (COFGT (1995)) (Equation (7)).

ROH +

CS2

S C

KOH

+

RO

–

S K

+

+

H2O

ð7Þ

The xanthates have been used as precursors for the synthesis of dithiocarbonic acid diesters, and for this purpose, within the review period, only the compounds with R = Et or i-Pr had been employed. The synthesis, spectral characterization, and X-ray structures of methylmercury(II) xanthates (MeOC(S)SHgR, R = Me, Et, i-Pr or Bn) have been reported <2002ICA71>. These compounds tend to form supramolecular, self-assembled, tape-like arrays in the solid state, whereas the compounds with R = Et or i-Pr form double chains, and the compound with R = Bn forms dimeric units that do not interact with one another. Within the review period, bisalkoxythiocarbonyldisulfides [ROC(S)SSC(S)OR] have been employed as precursors for the synthesis of dithiocarbonic acid diesters which are readily available by the oxidation of the alkali metal xanthates (Equation (8)). S C

2 RO

–

S K

+

S C

S C

Oxidation RO

S

S

ð8Þ OR

As oxidizing agents, the halogens, hypochlorite, bromocyan, and K2S2O8 have been mostly utilized, but other reagents have been employed as well. Yields were high and the bisalkoxythiocarbonyldisulfides are considered to be very useful, easy-to-handle reagents <1983HOU(E4)408> (COFGT (1995)). EtOC(S)SK+ in THF/H2O was used to synthesize the analogous bisethoxythiocarbonyl triand tetrasulfides (by the addition of SCl2 and ClSSCl, respectively), which are in use as new sulfur-transfer reagents for the sulfurization of the nucleoside linkage of oligonucleotides <1997USP14961> (Scheme 13).

S EtO C S – K +

S EtO C S – K +

THF/H2O +S2Cl2

S EtO C S S S S C OEt S

THF/H2O

S EtO C S S S C OEt S

+SCl2

Scheme 13

Functions Containing a Thiocarbonyl Group and at Least One Halogen 6.17.2.2.2

511

O,S-Diesters of dithiocarbonic acid

O,S-Diesters of dithiocarbonic acid have proven to be an invaluable class of compounds which play an important role in free-radical chemistry, such as for the deoxygenation of alcohols, radical cyclization, and isomerization <1983HOU(E4)408> (COFGT (1995)). These methodologies have found wide application in the synthesis of natural products and their analogs by favoring the radical process and suppressing the side reactions.

(i) From alkali salts of O-esters of dithiocarbonic acid For the preparation of the O,S-diesters of dithiocarbonic acid, mostly sodium or potassium xanthates were simply alkylated using common organic solvents <1983HOU(E4)408> (COFGT (1995)); yields ranged from good to excellent. The synthesis of S-vinyldithiocarbonates is not straightforward because nucleophilic substitution at the vinylcarbon is difficult. However, a general method for the preparation is now available: the reaction of potassium dithiocarbonate with vinylphenyliodonium salt in tetrahydrofuran (THF) occurs quickly and in high yield <1999JCR(S)432> (Equation (9)).

S RO C S – K +

+

R' CH CHI + PhBF 4–

THF rt

R'

CH CH S C OR S

ð9Þ

The reaction is stereospecific and retention of configuration was observed <1999JCR(S)432>. Though the conversion of tosyl-activated, optically active cyanohydrins with potassium ethoxide-dithiocarbonate as the S-nucleophile under SN2 reaction conditions in dimethylformamide (DMF) was complete after 1 h, it was observed that at least 20% recemization had occurred. Nevertheless, the yields were good (66–70%) (Equation (10)).

Me

O SO2 H R CN

EtO C(S)S – K +

S

DMF, 1 h rt

S

C OEt

R

H CN

R = n-Pr 97/95% ee

37% ee

R= i-Bu

72% ee

95/92% ee

ð10Þ

The nucleophilic displacement of the bromine atom in -bromo--thiobutyrolactone by the O-i-Pr-xanthic group has been achieved in 45 min (cf. Table 8, entry 1) <1999S577>. Using this procedure, a benzotriazolyl-O-ethylcarbonodithioate (cf. Table 8, entry 2) and a alkythioethynyl-O-ethylcarbonodithioate (cf. Table 8, entry 3) were synthesized. The xanthates CH2¼CHCH2CH(SC(S)OEt)CO2Et (from CH2¼CHCH2CHBrCO2Et) and PhC(O)CH(SC(S)OEt)CH2CH¼CH2 (from PhC(O)CHClCH2CH¼CH2) were also produced in good yields <1998SL1435> in addition to 5-O-Et-xanthomethyltetrazoles from the corresponding 5-chloromethyltetrazole <1998TL19>. 7-Cyclohepta-1,3,5-trienylethoxydithiocarbonate has been prepared in 95% yield by coupling tropylium tetrafluoroborate with potassium ethylxanthate in acetonitrile solution <1995MC133> (Equation (11)) (Table 9a).

512

Functions Containing a Thiocarbonyl Group and at Least One Halogen Table 8 Synthesis and properties of O,S-diesters of dithiocarbonic acid

Entry

Synthesis; yield (%)

O,S-diester

–

EtOC(S)S K

S C(S)OEt O

Stable orange oil IR, 1H, 13C

<1999S577>

White crystals m.p. 72 C 1 H, 13C

<2000H301>

Viscous liquid, cherry color IR, 1H

<2000PS81>

Yellowish oil IR, 1H, 13C

<1999TL277>

m.p. 41 C 1 H, 13C

<1999TC277>

O

S S

References

+

Br

1

Properties

Acetone, rt, 45 min; 100%

N N

N N

S

N N

CH2Cl

OEt +

–

2

EtOC(S)S K Acetone, rt, 4 h;

S

99%

–

RO C(S) K

EtS S C C S C(S) OEt

3

+

DMSO EtS C CCl rt, 60%

(EtOC(S)S)2

4

Me Me C N NC

Me S Me C S C Me OEt

2

Cyclohexane 3–4 h, reflux; 87%

(EtOC(S)S)2 N

5

CN

N N NC CN

2

Toluene 3–4 h, reflux; 87%

OEt S +

–

BF4

EtO C(S)S – K + Acetonitrile 0 °C, 4 h

S

ð11Þ H

95%

Both 1H and 13C NMR spectra indicate the pseudoaxial positioning of the ethoxydithiocarbonate group (1 structure) and the fast, reversible migration of the ethoxydithiocarbonate group along the perimeter of the cycloheptatriene ring that occurs through a series of [1,7]-sigmatropic shifts (G# (298 K) = 17.4–17.9 kcal mol1).

Functions Containing a Thiocarbonyl Group and at Least One Halogen

513

Table 9a Synthesis and properties of S-alkylcarbonyl xanthates S-alkylcarbonyl xanthate

Properties

EtO C(O) C(S)OEt

Bright yellow oil

C16H33O C(O) C(S)OEt

Bright yellow oil

O C(O) C(S)OEt

Bright yellow oil

Bright yellow oil

O C(O) C(S)OEt

O C(O) C(S)OEt

Bright yellow oil

C8H17 S EtO C S O

Pale yellow solid m.p. 88–89.5 C []D +9.7 , IR, 1H; yield 79%

H O

H O O C

OEt S C S

H AcO

Pale yellow solid m.p. 77.5–79.5 C []D 31 , IR, 1H; yield 52%

H

S C O

Yellow solid m.p. 133–134 C []D +38 IR, 1H; yield 48%

EtO C S Source: <1999T3791>.

The reactions of isomeric tetrachlorocyanopyridines with potassium Et-O-dithiocarbonate have also been studied: tetrachloro-2-cyanopyridine was converted successively into the 4-mono- and then the 3,4-bisethylxanthates; with additional potassium Et-O-dithiocarbonate, the last derivative undergoes intramolecular cyclization with formation of 1,3-dithiolo[4,5-c]pyridine <1997CHE1306>. For the other polychloromonocyanopyridines, substitution of the chlorine atoms by the ethylxanthate fragment was observed, sometimes accompanied by the loss of COS instead of heterocyclization <1997CHE1306>. New S-alkylxanthates have been synthesized via the S-alkoxycarbonyl xanthates <1999T3791>; the latter compounds were obtained from the corresponding alcohols by the dropwise addition of a solution of phosgene in toluene and the crude alkylchloroformates that formed (obtained in near quantitative yield) treated with potassium O-ethylxanthate in acetone. Finally, upon exposure of these yellow-colored S-alkoxycarbonylxanthates to visible light in an inert solvent under reflux, a smooth rearrangement took place affording the S-alkylxanthates in good yields (see Table 9a) <1999T3791, 1996CC1631> (Scheme 14) (Table 9b). When 5-hexenyloxycarbonylxanthate was irradiated under the same conditions, a cyclopentane derivative was isolated. S-alkoxycarbonylxanthates derived from various substituted 3-buten-1-ols behaved similarly, affording the corresponding lactones in all cases <1999T3791>.

514

Functions Containing a Thiocarbonyl Group and at Least One Halogen

R

ii. EtO C(S)S K

O S

R1 R3

S

O

hν

S S

OEt

S

hν

R

OEt

hν Toluene reflux

OEt

O

O

S

S C

S

O

R2

O

i. COCl2

R OH

OEt

S OEt

S C O

Toluene reflux

S

S OEt

R2

O R1

R3

Scheme 14

Table 9b Synthesis and properties of S-alkyl xanthates S-alkyl xanthate

Properties

EtS C(S) OEt

Yellow oil

C16H33S C(S) OEt

Yellow oil

S C(S)OEt

S C(S)OEt

S C(S)OEt

S C S

H

EtO

Colorless liquid, IR, 1H; yield 61% Colorless liquid, IR, 1H; yield 59% Colorless liquid, (2:1 (E)/(Z))IR, 1 H; yield 52% White solid (4:1 mixture of epimers), 3-isomers: m.p. 103-106 C,[]D+30, IR, 1H; yield 71%

S S C OEt

White, crystalline solid,m.p. 185–186 C,[]D 26, IR, 1H; yield 83%

H

Colorless oil,[]D +57, IR, 1H; yield 92%

S C S EtO S S C OEt

Source: <1999T3791>.

Colorless oil, IR, 1H; yield 87%

Functions Containing a Thiocarbonyl Group and at Least One Halogen

515

Potassium O-furfuryl dithiocarbonates have been employed as reactive intermediates for a simple synthesis of furfuryl sulfides via extrusion of COS <1995JCS(P2)1155>.

(ii) From bisalkoxythiocarbonyl disulfides For the preparation of carbohydrate-derived S-xanthates which are attractive due to their importance as precursors for osides or anomeric activators (i-PrOC(S)S)2 was used. The introduction of the S-xanthate group was regiospecific and led to reasonable yields with reaction at the primary and anomeric hydroxyls of the sugars <1999OL521> (Scheme 15).

HO Oside

HO

Oside

i -PrOC(S)S

Bu3P, (i -PrOC(S)S)2

Carbohydrate

i -PrOC(S)S

Bu3P, (i-PrOC(S)S)2 Toluene, 1 h

Toluene, 1 h

Carbohydrate

Scheme 15

A complete selectivity for the primary hydroxyl site was observed for diol substrates possessing a secondary hydroxyl function, though the reaction appeared to be quite sensitive to steric effects. The direct conversion of the anomeric hydroxyl into O-alkyl, S-glycosyl dithiocarbonates in high yield reveals the efficiency of the method <1999OL521>. A number of sterically hindered tertiary S-alkyldithiocarbonates were synthesized by the decomposition of tertiary diazoderivatives (which can easily be made from the corresponding ketone hydrazones) in the presence of dithionosulfides in good yield (cf., e.g., entries 4 and 5 in Table 8) <1999TL277> (Equation (12)). R1 R1 R 2 C N N C R2 E E

(ROC(S)S)2 ∆, –N 2

S R1 R2 C C E OR

ð12Þ

Two malonate xanthate derivatives were synthesized directly by reaction of the enolates of the starting materials with diethyldithiobis(thioformate) (Scheme 16).

COOEt

i. LDA, THF –78 °C ii. (EtOC(S)S)2

COOEt S

0 °C 58%

COOEt COOEt

i. NaH, DMSO benzene ii. (EtOC(S)S)2 rt 50%

EtOOC

C S

OEt

COOEt S

C S

OEt

Scheme 16

This is a direct way of transforming carbanionic centers into proradical ones, resulting in the ‘‘Umpolung’’ of active methylene compounds.

516

Functions Containing a Thiocarbonyl Group and at Least One Halogen

(iii) From carbon disulfide The preparation of O,S-dithiocarbonates directly from the alcohols by reaction with a base, CS2, and a haloalkane has been used widely (COFGT (1995)). In the typical reaction procedure, the alcoholate is produced with NaH in THF, and catalytic amounts of imidazole, CS2, and the halomethane are then added sequentially. A number of applications of this procedure have been reported after 1995. 2,2-Dimethyl-1,3-dioxan-5-ols have been converted into the corresponding methoxydithiocarbonates in good yields in the course of highly diastereoselective and enantioselective syntheses (de 98% and ee = 92–98%) <1998EJO2839> (Equation (13)). S OH R2 O

O

i. NaH ii. CS 2

R1

iii. MeI

O

SMe R1

R2 O

ð13Þ

O

82–93% R1, R2 = Me, Et, i -Pr, Bn, CH2OBn, CH2O(CH2)2TMS

Employing the same procedure, S-propargylxanthate (BnOC(S)SCH2CCH) was synthesized from benzyl alcohol using propargyl bromide as the alkylating agent <1998TL7301>. A tricyclic sulfide with C2 symmetry was synthesized via a radical-mediated route from the xanthate (prepared in excellent yield of 90% from the corresponding dibenzylidene acetal) using tributyltin hydride in toluene and ,-diazoisobutyronitrile as initiator <2001TL7091> (Scheme 17). The 3-O-xanthyl-1,2-cyclopropylglucal derivative, synthesized similarly from the corresponding secondary alcohol, was used for the formation of 1-C-methyl-2,3-unsaturated sugars via tri-nbutyltin hydride-mediated ring opening <2001CL103>. Ph OH O

O

O

O

OH

Ph

O O HO

O

Ph

SMe NaH THF CS2 MeI rt 90%

NaH THF CS2 MeI rt 87%

S O

O

O

O

Bu3SnH AIBN Toluene 80 °C, 16 h

O

O

Ph

O

O

Ph O

O S

S Ph

MeS

O O MeS C O S

78%

O

Bu3SnH AIBN

O O

O Me

Benzene reflux, 2 h (α )D 63° 67%

Scheme 17

Other O,S-dithiocarbonates have been synthesized using the NaH/CS2/MeI method <1993TL2733> as suitable precursors for radical group transfer azidation <2001JA4717>, for an intramolecular carbocyclization in the course of the total synthesis of (+)-eremantholide A and ()-verrucatol <2000MI3>, for the O,S-dithiocarbonates <2001TL859, 2001JOC1061>, for the deoxygenation of primary <1998TL2483> and secondary alcohols in the course of the total syntheses of macrolide antibiotics <1998JA5921> and (R)-()-2,4-diphenylbutyric acid <2000JOC5371>, and for the synthesis of trifluoromethyl ethers by oxidative desulfurization– fluorination of the trifluoromethylated xanthates (cf. Table 10) <2000BCJ471, 1998BCJ1973>. Allyl alcohols adsorbed on Al2O3KF at room temperature reacted with CS2 and methyliodide to provide the S-allyl-S-methyl-dithiocarbonates (R1R2C¼CHCR3OC(S)SMe) <1995SC2311>. Yields were in excess of 50%, and the products, yellow liquids, were characterized by 1H and 13 C NMR and MS.

517

Functions Containing a Thiocarbonyl Group and at Least One Halogen Table 10 Synthesis and properties of S-aryl and S-alkyl xanthates <2000BCJ471> S R O C SMe

Compound

Yield (%)

Properties

4-Me–C6H4– 4-Br–C6H4–CH2CH2– n-C16H33 –

Pale yellow oil IR, 1H, MS

82

Pale yellow oil IR, 1H, 13C, MS

99

Pale yellow oil IR, 1H, 13C, MS

88

OCS2Me

OCS2Me

Br OCS2Me

Pale yellow oil IR, 1H, 13C, MS

97

Pale yellow needles m.p. 106–107 C IR, 1H, MS

91

Pale yellow oil IR, 1H, 13C, MS

99

(iv) From CS2 and methyl iodide 1-(Methyldithiocarbonyl)imidazole, a yellow oil that has been characterized by 1H NMR, was produced by the reaction of imidazole with CS2 and methyl iodide in the presence of sodium hydride (vide supra). Xanthates result from the reaction of alcoholates (deprotonated using NaH in THF) directly with 1-(methyldithiocarbonyl)imidazole at room temperature <1997SL1279> (Equation (14)).

N

+

–

N

Na

i. CS2,THF, 0 °C ii. MeI

S N

98%

Base R-OH

N C SMe

S RO C

ð14Þ

SMe

>95%

The conversion of alcohols to O-alkyl, S-methyl dithiocarbonates using 1-(methyldithiocarbonyl)imidazole proceeds efficiently; primary, secondary, tertiary, benzylic, and aromatic alcohols all reacted to provide products in high yields (>95%).

(v) By radical addition to alkenes O,S-Diesters of dithiocarbonic acid added efficiently to unactivated alkenes by a radical mechanism to provide the corresponding adducts (Scheme 18).

R

S

S C

OR'

Initiator

R''

R'' R

R

R

S

S C

R'' OR'

S R

S C OR'

Scheme 18

When trifluoromethyl xanthates were employed, the trifluoromethyl group added to the least hindered site of the alkene <2001OL1069>. The xanthate methodology is applicable for additions to strained alkenes such as cyclobutenes, azetines, and cyclopropenes <2000TL9815>.

518

Functions Containing a Thiocarbonyl Group and at Least One Halogen

The intermolecular addition of the radical obtained from the xanthate to suitable allylic or homoallylic amines proved to be the key step for the construction of various nitrogen heterocycles <1999TL3701>. By the same procedure, the electrophilic alkyl radicals served as useful precursors for annulation reactions and afforded cyclopentane derivatives in moderate-to-good yields <1998SL1435>. Substituted S-phenacyl xanthates add intermolecularly to various alkenes <1997TL1759> and sterically hindered xanthates, and by the same process, add to allyl acetates and allyltrimethyl silane <1999TL277> and to allyl- and vinylboronates <2001CC2618> to provide the expected products. The synthesis of benztriazole xanthates has been realized using a clean, efficient, and nontoxic xanthate radical process <2001H301> (Scheme 19). N N N CH2 Cl

EtOC(S)S – K Acetone 20 °C, 4 h

Peroxide or hν R

N

+

N N

CH2

S

OEt S

N

N

N

N

N

N CH2

CH2

CH2

R CH S C S EtO

Scheme 19

The addition of the benzotriazol-1-yl methyl radical was observed to be regiospecific with the benztriazol-1-yl methyl moiety adding to the unsubstituted side of an alkene double bond. The existence of the radical could not be proven by ESR spectroscopy, but by-products which could only originate from the formation of the benzotriazol-1-yl methyl radical strongly implied the existence of such.

(vi) By other methods A novel and convenient preparation for steroidal 1,3-oxathiolane-2-thiones (cis cyclic dithiocarbonates) at room temperature in high yields has been reported by the reaction of steroidal 5,6epoxides with CS2 in THF using lithium bromide as catalyst <1997TL5705> (Equation (15)). C8H17 CS2, LiBr THF, rt 70–83%

R

ð15Þ

R O

O

S S

R = H, OAc, Cl

The cis products were obtained selectively as the sole products. The reactions of various oxiranes with CS2 under the same reaction conditions have also been examined <1995JOC473>. The desired dithiocarbonates were obtained regioselectively in high yields, and the formation of the regioisomeric trithiocarbonates and episulfides was suppressed (Equation (16)). S

S O R

CS2

O

S

S

Cat. R

R

S O ,

S R

S ,

S

ð16Þ

R

The selectivity and yield of the reactions were strongly reduced when other alkali halides were applied as catalysts <1995JOC473>. Using this method, 4-arylspiro[1,3-oxathiophene-2-thione]5-tetral-1-one was prepared <2001MI365>.

Functions Containing a Thiocarbonyl Group and at Least One Halogen

519

A facile, one-pot synthesis of a number of insecticidal thiophosphoryl xanthates was performed using the mild base 1,8-diaza[5,4,0]bicycloundeca-7-ene in the DBU-catalyzed sequential reaction of various alcohols ROH (R = allyl, i-Bu, n-Bu, s-Bu, 2-Ph-ethyl, furfuryl; all in excess) with CS2 and diethoxyphosphoryl chloride <2001SL625> (Equation (17)).

DBU, CS2

R OH

R O

0 °C

S C

SH

S

ClP(S)(OEt)2

R

rt

O

S P OEt S OEt

ð17Þ

65–88%

The catalyst in this reaction is mild and can be removed from the reaction mixture simply by washing with water. Another mild, chemoselective, and efficient protocol for the thiocarbonylation of alcohols and the thiocarbamation of amines has been reported using CS2 and alkyl halides in the presence of caesium carbonate and tetrabutylammonium iodide (TBAI) <2001TL2055> (Scheme 20).

R OH +

R NH2

R' X

+

R' X

S

CS2, CsCO3, TBAI R

DMF, 0 °C to rt

O

CS2, CsCO3, TBAI

R'

S R

DMF, 0 °C to rt

S

N H

S

R'

Scheme 20

For the syntheses of various arylseleno- and aryltellurothionoformates (PhOC(S)SeAr and PhOC(S)TeAr, respectively), commercially available phenyl chlorothionoformate was reacted with (Me3Si)3SiSeAr and (Me3Si)3SiTeAr, respectively, and 4 mol.% of tetrakis(triphenylphosphine)palladium. Yields were excellent, 86–96% after chromatography, and the products were identified unequivocally by 125Te and 77Se NMR <1998JOC5713>.

6.17.2.2.3

Sulfoxides of O,S-diesters of dithiocarbonic acid (sulfines)

Xanthates have been oxidized using MCPBA in CH2Cl2 at 0 C <1997JCS(P1)2019> (Equation (18)). O

S R1O

MCPBA SR2

CH2Cl2

S

R1O

S SR2

(E )

+

R1O

O SR2

ð18Þ

(Z )

NMR analysis of the sulfines (performed rapidly after reaction) showed that the (E)-isomer was predominantly obtained (R1 = i-Pr, R2 = Bn), revealing that oxygen transfer occurs to the opposite side of the SR2 group. However, for another sulfine (R1 = 2,6-di-t-Bu-phenyl, R2 = Me), the same analysis yielded the reverse result with an (E):(Z) ratio of 8:92. This sulfine could be kept without change for months at ambient temperature in contrast to the preceding one which transformed into a mixture of thiocarbonate and dithioperoxycarbonate upon standing. The sulfine structure was determined by X-ray analysis which provided a C¼S bond length of 1.669 A˚ and an S¼O bond length of 1.506 A˚. The plane of the sulfinyl group is perpendicular to the plane of the phenyl ring and the C(7)–(S(2) bond has an s-trans arrangement in contrast to the s-cis conformations of esters, thioesters, and dithioesters <1997JCS(P1)2019>.

520 6.17.2.3

Functions Containing a Thiocarbonyl Group and at Least One Halogen Thiocarbamates (Esters of Thiocarbamic Acid)

The free thiocarbamic acids (H2NC(S)OH and its analogs) cannot be isolated because they decompose spontaneously to COS and the corresponding amine, but their salts have been prepared <1983HOU(E4)408> (COFGT (1995)).

6.17.2.3.1

From O-alkyl or O-aryl chloroformates and amines

By reacting the easily available thiocarbamic ester chlorides with primary and secondary amines, the thiocarbamic acid O-esters can be synthesized. Inert solvents, e.g., chloroform or THF, were used, sometimes in the presence of a base for neutralizing the HCl produced. By this procedure, aryl thiocarbamates (for the further synthesis of caffeic acid) were readily obtained <2000JOC6237> (Scheme 21).

NH2

H N

S PhO C

OPh

Cl S

R

R THF rt H N O

S

R1

PhO C Cl

R2

O

S C OPh N R1 O R2 O

Scheme 21

Similarly, by using pyridine as the base, isoxazol-5(2H)-ones were reacted with thiocarbamoyl chloride (and with various other thiocarbonyl chlorides) to provide the N-thioacetylated derivatives in moderate-to-good yields and with the formation (5%) of the competing O-thioacetylated isomer <1998JCS(P2)3245>. To overcome the side reactions of the chloroformates, tertiary aliphatic amines were dealkylated <1998TL4387, 1999AJC841> (Scheme 22).

S R3N

PhO

S

CH2Cl2

+ Cl

(N2), 1 h

PhO

NR2

+

RCl

70–95% R3 = Me3, Et2Bn, Me, morpholine, Me2cinnamyl, quinuclidine, tropine, bicuculline, Me2t-Bu

Scheme 22

Instead of chloroformates, the corresponding bis(ethoxythiocarbonyl)sulfide was employed to synthesize the thiocarbamates of glucosamines <1996JA3148> and the dithiasuccinoylamino protecting group for the solid-state synthesis of peptide nucleic acids <1999JOC7281>.

Functions Containing a Thiocarbonyl Group and at Least One Halogen 6.17.2.3.2

521

From N,N-dialkylthiocarbamoylchlorides and alcohols or phenols

This reaction proved to be another general method to prepare the corresponding thiocarbamates by the reaction of alcohols with N,N-dialkylthiocarbamoylchlorides <1983HOU(E4)408> (COFGT (1995)). Further examples of this method have been published after 1995. The 1:2 mixture of diastereomeric meso- and rac-diols was converted into the corresponding dithiocarbamates in good yield with retention of the diastereomeric ratio; the pure mesocompound yielded only the meso-dithiocarbamate <2000T5413> (Equation (19)). S OH

i. NaH, THF

R

Me2N

R

ii. Me 2NC(S)Cl

OH

ð19Þ

O C S Me2N

77–89% R =C

O

CH, Me

A number of thiocarbamates of 5-O-benzyl-1-O-methylribofuranoside were synthesized by the reaction of the sodium salt with several thiocarbamoyl chlorides in THF. Yields were in excess of 80% and the thiocarbamates were employed as glycosyl donors for the stereoselective synthesis of -D-deoxyribonucleotides. The best result, : = 4:96, was obtained for the diethylcarbamate <1996CL99>. In the above reaction, the -side of the glycosyl donor, was efficiently blocked by the O-thiocarbamoyl group and the reaction proceeded under the remote stereocontrol of the O-thiocarbamoyl directing group <1996CL629, 1997CL389, 1998MI101> (Equation (20)). Bn

O

i. NaH, THF, rt

Bn

O

OMe

OH

ii. R2NC(S)Cl

O

OH NR2

ð20Þ

S NR2 = NEt, NMe2 , N

O

Many more phenol derivatives have been reacted by this procedure <2002T2831, 2001JOC2104, 1995LA2221, 1995SL155, 1996SC2461, 1996SL1054, 1997SC2487, 1998TA2819, 1998TL9639, 1999CC2169> (cf. Table 11). In one case <1998TL4219>, the thiocarbamate of a cross-conjugated cyclopentenone derivative was synthesized (Scheme 23).

6.17.2.3.3

From N,N 0 -thiocarbonyl diimidazole and alcohols

The mild procedure of functionalizing alcohols by employing thiocarbonyl imidazolides as intermediates is a standard procedure these days for the dehydroxylation of secondary alcohols. The yields are high, but only in a few cases the thiocarbonyl imidazolides were isolated <2002TA759, 2000T5819, 2000MI559, 1998JA1747, 2000T7173> (cf. Table 12), otherwise they were used further without purification <1998CC871, 1999TL6979, 1999AP435, 2000H637, 2000H1885, 2001TL8625, 1995JA10889, 1995CC719, 1996CC1661, 1997SL387> (Scheme 24).

6.17.2.3.4

From thiophosgene and 1,2-amino alcohols

Cyclization of the 1,2-amino alcohols with thiophosgene and triethylamine in methylene chloride gave an oxazolidinethione in 95% yield as a viscous oil which crystallized after several weeks. The oxazolidinethione was finally acetylated with n-BuLi and n-PrCl in THF at –78 C to provide the propionyloxazolidinethione in 90% yield <2001JOC894> (Scheme 25). By the same synthetic procedure, ()-(hydroxyoxindol-3-yl)methylammonium chloride was treated with thiophosgene to provide the desired product with a spiro ring system in 92% yield as colorless crystals which were characterized by IR, 1H, and 13C NMR, UV, and MS <2001JOC3940>. Alkylation using methyl iodide, however, provided the S-alkylation product.

522

Functions Containing a Thiocarbonyl Group and at Least One Halogen Table 11 Thiocarbamates obtained from thiocarbamoyl chlorides

Compound Me2N(S)CO C

C

CH

OC(S)NMe2 S Me2NC O

O

O

Synthesis; yield

Properties

References

(a) NaH, THF, 20 C (b) Me2NC(S)Cl, 20 C; 98%

meso m.p. 134 C, 1H, IR rac m.p. 89–90 C, 1 H, IR

<2000T5413>

(a) NaH, DMF (b) Me2NC(S)Cl, 96%

m.p. 103–104 C MS, 1H, 13C

<2002T2831>

(a) NaH, DMF (b) Me2NC(S)Cl, rt; 83%

Yellow solid m.p. 126 C IR,1H, 13C, MS

<1995LA2221>

ArOH/acetonitrile Me2NC(S)Cl, KF (on alumina); 58%

Red, viscous liquid 1H

<1996SC2461>

Et2N-C(S)Cl, DMAP, TEA, 1,4-dioxane reflux; 71%

Light tan crystals m.p. 73–75 C 1 H, MS

<1997SC2487>

DMF, NaH, Me2NC(S)Cl, 85 C; 80%

Colorless crystals m.p. 132–195 C 1 H

<1998TA2819>

THF(N2), NaH, THF, Me2N-C(S)Cl, rt; 77%

m.p. 79–81 C 1 H

<2000MI547>

CHO O

NMe2 S

S O

NMe2

S O

NEt2

OMe

S S C NMe2 Me2N C O O

MeO OMe Me OHC

OC(S)NMe2

-D-Mannopyranosylamine also reacted with thiophosgene under the conditions described above, whereby a cis-bicyclic thiocarbamate resulted. The corresponding trans-hydrindane-type isomer, produced from the corresponding -D-glucopyranosyl derivative, was not that stable due to the strain resulting from the ring fusion <2001TL5413> (Scheme 26). When oligosaccharides were reacted with thiophosgene, the bis[cyclic thiocarbamate]s were the only products that could be isolated <1995CC57>.

6.17.2.3.5

From CS2 and 1,2-amino alcohols

This last reaction was also accomplished using CS2/triethylamine in THF; however, the yields were lower <2001JOC894> (Scheme 27).

Functions Containing a Thiocarbonyl Group and at Least One Halogen S

S Ar – OH

+

R2N C

523

Ar O C

NaH, DMF, rt

NR2

Cl

O

O

OEt

HO

Me2N C(S) – Cl

+

O

O CH2Cl2 DABCO 0 °C

OEt

O

Me2N

S

84%

Scheme 23

The relative configurations of the vicinal hydroxy and amine substituents of -hydroxyhistidine derivatives were determined by transformation into the corresponding oxazolidine-2-thiones using CS2/TEA. The cis or trans configuration was easily determined by 1H NMR; for a cis stereoisomer JH,H lies in the range 8–9.5 Hz, and for a trans arrangement JH,H lies in the range 5–8 Hz <1998JOC2731>. Other 2-oxazolidinethiones have also been synthesized employing this synthetic procedure (cf. Table 13) <1995JOC6604, 1997H2471, 1999SC1627>. The corresponding six-membered, 2-thiono-1,3-O,N-heterocycles were also produced by reaction of the corresponding amino alcohols with carbon disulfide in the presence of trimethylamine at room temperature <2001T3175> (Scheme 28). The cis or trans configuration of the ring anellation of the two six-membered rings follows from the values of the J-couplings of H-8a (two 3Jax,ax couplings are observed in the case of the trans isomer but only one in the case of the cis isomer). The corresponding oxazolo[4,5-b]pyridine-2(3H)-thione was synthesized by the reaction of 2-hydroxy-3-aminopyridine with potassium ethylxanthogenate <1997CHE1337>; the thione structure of the compound was established by both 1H NMR and X-ray diffraction.

6.17.2.3.6

From isothiocyanates and alcohols

The addition of alcohols to isothiocyanates is useful as another general method for the preparation of O-alkyl thiocarbamates. Some examples of the procedure that have been reported include <2002HAC280, 2001CAR123, 2001CPB361, 2001H279, 2000PS221, 1997CCC1491> (cf. Table 14) (Equation (21)).

R N C S

EtOH

∆

S R NH C

ð21Þ

OEt

Triethylamine and sodium alcoholates were found to strongly accelerate the reaction. Phenols only add poorly to the phenyl isothiocyanates. The S-alkyl esters of N-alkyl(aryl) dithiocarbamic acid were converted into the corresponding O-alkyl(aryl)esters of N-alkyl(aryl)thiocarbamic acid using alkali metal alkoxides in the presence of one or more alcohols as solvents <1997MIP5621132>. In the presence of base, the formation of a six-membered cyclic thiocarbamate is slow, resulting from intramolecular nucleophilic addition of the C(5) hydroxyl group to the heterocummulene functionality of the furanose form, was observed <2000CAR218> (Equation (22)).

524

Functions Containing a Thiocarbonyl Group and at Least One Halogen Table 12 Thiocarbonylmidazoyl derivatives obtained from the corresponding secondary alcohol

Compound N

POPh2 N

C S

O

POPh2 N

N

C S

O

Me

Properties; yield

References

cis: While solid, m.p. 192–193 C, IR, 1H, 31P, MS; 65% trans: Brown solid m.p. 172–173 C IR, 1H, 31P, MS

<2002TA759>

Pale yellow oil, 1H; 84%

<2000T5819>

White solid m.p. 135–137 C, MS, 1H; 81%

<2000MJ559>

NOMe

TOS

NH2 N O

O

N

N S

O

O

F

N

Si Si

O C

O

N

COOMe H S C N O

R

N

N

R=H

Pale yellow solid, 1 H, 13C, IR, MS; 85%

R = Me

White solid, 1H, IR; 77%

13

C,

<1998JA1753>

OH

S O O

O

N

N

OTBS

Colorless oil, IR, 1H, 13C, MS; 82%

<2000T7173>

Colorless oil, IR, 1H, 13 C, MS; 56%

<2000T7173>

Yellow oil, IR, 1H, 13 C, MS; 89%

<2000T7173>

Yellow oil, IR, 1H, 13 C, MS; 73%

<2000T7173>

O S O C N

N

OTBS

S O O

N

N

OTBS

SBTO S O O

SBTO

N OTBS

N

525

Functions Containing a Thiocarbonyl Group and at Least One Halogen N R1 R2

+

CH OH

S C N

S

Benzene, 80 °C NaH reflux

N

R1 R2

CH O

N

N

N

R1 R2

CH2

Scheme 24

S OH

NH2

S CCl2 Et3N CH2Cl2

n-Bu

HO

+

HN

O

–

N

O

S

O O

CH2Cl2

N H

S

n-Bu

S CCl2

O

Me

n-Bu

H N

NH3Cl

O

n-BuLi THF EtCOCl

N H

Scheme 25

S HO HO

OH OH O

HO HO

NH2

O

HO HO

NH2

OH

HO OH

O

H N

S

O

HO HO

NH

OH

OH HO HO

OH O O

O OH

HO O

OH

S CCl2

OH OH

Pyridine

Scheme 26

O H N OH O OH S

O

OH O N

H

S

526

Functions Containing a Thiocarbonyl Group and at Least One Halogen S

HO COOEt N SO2Ph

O

CS2 , Et 3N CH2Cl2 rt

NH

NH2 N SO2Ph

COOEt

S

HO

O COOEt

N SO2Ph

NH2

CS2 , Et3N CH2Cl2 rt

NH N SO2Ph

COOEt

Scheme 27

Table 13 2-Oxazolidinethiones as synthesized from the corresponding -amino alcohols Compound

Synthesis; yield

Properties

O

HOH2C

S N H

References

CS2, H2O2, base; 100%

Colorless crystals m.p. 57.5–59.5 C 1 H

<1997H2471>

CS2, KOH, Pb(NO3)2, H2O; 20%

White solid m.p. 94 C 1 H, 13C

<1999SC1627>

CS2, KOH, Pb(NO3)2, H2O; 14%

White crystals m.p. 54 C 1 H, 13C, MS

<1999SC1627>

CS2, Et3N, NaOH; 63%

Oil []D 93 1 H

<1995JOC6604>

CS2, Et3N, NaOH; 60%

White solid m.p. 142–143 C []D 187.3 1H, 13C

<1995JOC6604>

O S N H O S N H O S PhH2C Me Me PhH2C

N H O S N H

HO NH2 Ph H

S CS2, Et3N CHCl3 rt

O NH Ph H

47%

Ph H

OH NH2

CS2, Et3N CHCl3 rt 43%

Scheme 28

Ph H

S O NH

527

Functions Containing a Thiocarbonyl Group and at Least One Halogen Table 14 O-Alkyl thiocarbamates synthesized from the corresponding isothiocyanates Compound

Synthesis; yield

Properties

References

COOEt S

N

S

EtOOC

NH C OEt

EtOH (anh.) reflux; 72%

Yellow crystals m.p. 116–117 C IR, 1H,13C,MS

<2002MAC280>

NaH/MeOH; 0 C; 78%

Pale brown crystals m.p. 103–104.5 C []D 23.1 1 H

<2001CAR123>

ROH reflux; 85%

Red needles m.p. 130–138 C IR, 1H

<2001H279>

Ethyleneglycol reflux; 69%

m.p. 205–207 C IR, 1H

<2000PS221>

NaOMe, ether (N2); 65%

m.p. 48–50 C IR, 1H, 13C

<1997CCC1491>

O H N

N

morph F

C S

OEt

S H

N

OEt

+

–

CH3 CF3SO3

HN

S C

OH

O

N S

N

OEt Et CH

S

NH C OMe

RO RO

N C S O OR OR

H DMF Et3N 80 °C 100%

S

N O OH

O

OH

ð22Þ OH

[α] D–35.5°

Isothiocyanates, under Evans conditions (Sn(Otf)2, N-ethylpiperidine) (COFGT (1995)), afforded the syn-aldol which was isolated as an intramolecularly derivatized heterocycle in moderate chemical yield but with syn/anti selectivity <1995TL7081> (Equation (23)). F NO2 OO

O

i. Sn(OTf )2 N-Et-piperidine

N Bn

N C S

THF ii. 4-F-3-NO2-benzaldehyde

OO

O

ð23Þ

N Bn

O HN S

The photolysis of O-allyl- and O-but-3-enyl-N-phenylthiocarbamates in benzene readily provided the corresponding S-allyl- and S-but-3-enyl-N-phenylthiocarbamates in good yields <1995JCS(P2)373>.

528

Functions Containing a Thiocarbonyl Group and at Least One Halogen

6.17.2.3.7

N-acyl-1,3-oxazolidine-2-thiones as auxiliary agents

N-acyl-1,3-oxazolidine-2-thiones have been employed for auxiliary-based, highly diastereoselective aldol additions. For the enolization, TiCl4/TMEDA <1997JA7883>, TiCl4/()-sparteine/N-methylpyrrolidine <2002OL2253>, Sn(OTf)2/N-Et-piperidine in CH2Cl2 (45 C) <1998JCS(P1)9>, or Ti(Cl)4/ DIPA in CH2Cl2 (78 C) <2001TL5085> (followed by an aldehyde) have all been used (Equation (24)). S O

O

S TiCl4/ – sparteine

N

CH2Cl2, then RCHO

Ph Ph

O

O

S

OH R

N

+

Ph

O

O

N

OH R

ð24Þ

Ph Ph

Ph 92:8 to 98:1

Other 1,3-oxazolidine-2-thiones for the highly stereoselective construction of CC bonds are known (Scheme 29). S O

O N

R

R = Me, Et, Bu, Ph

O O

N S

O N

S

R = Me, Et, i-Pr, Ph, Ph(X)

O

R

Scheme 29

The camphor-based, chiral N-acetyloxazolidinethiones have been used as starting materials for: (i) a one-step enolate bromation–aldolizaton reaction to provide bromohydrins (with yields in excess of 90%; additionally, the asymmetric induction of this reaction was shown to be exceptionally high) <1999TL3577, 1999JOC6495, 1999TA3249, 2000JOC6752>; (ii) a racemizationfree deacetylation of 3-acyl-1,3-thiazolidine-2-thiones <1999CC545>; and (iii) an asymmetric synthesis of -mercapto carboxylic acid derivatives <2001JA5602> (Equation (25)). OH O i. TiCl4, DIPEA Me

C N

O

6.17.2.3.8

S

R

ii. Br2IPIPEA iii. RCHO

O

N

ð25Þ

Br S

By thermal conversion of 2-allyl thiobenzothiazoles

The thermal conversion of 2-allyl thiobenzthiazoles <2000CHE201> and O-methyl-S-allyl-N-acridinyl iminothiocarbonates <1998H505> to the corresponding thiones has been reported to occur successfully with yields greater than 60% (Scheme 30). This S ! N allylic rearrangement is the result of a concerted [3,3]-sigmatropic shift.

6.17.2.3.9

Other methods

The oxo groups in 6-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones could be replaced by sulfur by the fusion (melting) of the diones with tetraphosphorus decasulfide <2000EJM733> (Equation (26)).

529

Functions Containing a Thiocarbonyl Group and at Least One Halogen

N

N

∆

S

S

O

O

OMe

OMe S

∆

N Acr R

S

N

Acr R

Scheme 30

O

O

O

P4S10

N

Cl

+

N

Cl

S R

R

S N

Cl

O

O

O

S

ð26Þ R

The products were isolated in yields below 50% after column chromatography, and the structures were confirmed by IR and 1H and 13C NMR. Cyclic thionecarbamates were usually prepared by the reaction of amino alcohols with CS2 or thiophosgene (vide supra); treatment of 3-hydroxybutylisocyanide with sulfur in the presence of 5 mol.% selenium and Et3N in refluxing THF for 3 h resulted in the formation of 1,3-oxazine2-thione in 79% yield <1997PS335> (Equation (27)). OH

R S (5 mol.% Se)

R

NC

HN

Et3N THF, reflux

O

ð27Þ

S

62–89% R = Me, Ph, CH2Cl

Oxazolidine 2-thiones were synthesized from alkenes by employing one-pot Co(II)-catalyzed epoxidation followed by cleavage with trimethylsilylisothiocyanate <1996TL7315> (Equation (28)). Ph

O

i. Co (II), O2, (CH3)2CH – CHO

Ph Ph

S

ii. Me 3Si – N C S, Co(II)

N H

Ph

ð28Þ

56%

The reaction is highly regio- and stereoselective as only one isomer was obtained and careful analysis of the reaction mixture indicated the total absence of the other regioisomer. The yields of the oxazolidine 2-thiones are improved considerably by using the epoxide instead of the alkene <1996TL7315>. In an approach to artificial nucleoside synthesis, a sugar-derived 1,3-oxazolidine-2-thione was produced from free or partially-protected sugars in one step using potassium thiocyanate under acidic conditions <2001TL2977> (Equation (29)).

Sugar

H N

KSCN, HCl, H2O

O

80–100% OH

S O

ð29Þ

OH

The structure of the sugar ring was clearly defined with formation of a furanose ring, confirmed by 1H and 13C NMR, and an anomeric configuration controlled by the hydroxyl located on C(2). Novel, convenient syntheses of 1,3,4-oxadiazol-2-(thi)ones from N-t-Bu-diacylhydrazines have been reported by reaction with t-BuOK followed by treatment with thiophosgene <2001S1965> (Equation (30)).

530

Functions Containing a Thiocarbonyl Group and at Least One Halogen O R

N H

But N

R' O

O

i. t-BuOK / THF ii. C(S)Cl 2

R

N

N

R'

O

70–80%

ð30Þ

S

R, R' = alkyl, aryl

6.17.2.4

Dithiocarbamates (Esters of Dithiocarbamic Acid)

The dithiocarbamic acids have been obtained from their alkali metal dithiocarbamates by treatment with HCl. However, they easily decompose in aqueous solution to produce CS2 and the corresponding amines (COFGT (1995)). N,N-diphenyldithiocarbamic acid (m.p. 147 C after recrystallization from benzene) and the N-acyldithiocarbamic acids (2-oxopyrrolidide, m.p. 101–102 C; and 2-oxopiperidide, m.p. 103–105 C), however, are sufficiently stable to permit isolation <1983HOU(E4)408>. Recently, ethoxydithiocarbamic acid [EtO2CNHC(S)SH] was isolated as pale yellow crystals and unequivocally characterized by IR and 1H NMR. Upon standing in the air, it dimerizes to form [EtO2CNHCS2]2.

6.17.2.4.1

Alkali metal salts of N,N 0 -disubstituted dithiocarbamic acid (dithiocarbamates)

Dithiocarbamates are usually prepared from CS2 and 2 equiv. of an amine using common solvents such as acetone or ethanol. When the reaction was performed in aqueous NaOH or KOH <1983HOU(E4)408> (COFGT (1995)), the corresponding sodium or potassium dithiocarbamates were obtained (e.g., sodium 1,10 -ferrocene-bis(dithiocarbamate) <1999SC1041> or potassium 1,1-dioxothiolan-3-yl-dithiocarbamate <2000MI1014>); in ammonium hydroxide solution, the ammonium dithiocarbamate was obtained <2001JIC372>. The dithiocarbamate anions are good ligands for transition metals and a large number of complexes have been constructed incorporating them. The sodium salts of the dithiocarbamates were normally used, and the complexes obtained ([R2NC(S)S]TeMe2 <1997IC1890>, [R2NC(S)S]AsPh <1995PS13>, [MeC(S)NHC(S)S]M (M = K, Rb or Cs) <1995ZAAK439>, [R2NC(S)S]GeClPh2 <2002IJC(B)1510>, [RHNC(S)S]SnCy3 <2002MI13>) were characterized by X-ray diffraction.

6.17.2.4.2

Esters of dithiocarbamic acids

(i) From carbon disulfide and base followed by alkylation The synthesis of the esters of dithiocarbamic acid is conventionally separated into two steps: the first step is the synthesis of the dithiocarbamates by reaction of a secondary amine with CS2 in the presence of a base; the second step is the alkylation of the dithiocarbamate salts, thereby converting them to the corresponding S-esters (Equation (31)). R1 NH + CS2 R2

KOH

R1 S N C – + R S K

MeI –KI

R1 S N C R S Me

ð31Þ

Following this procedure, the methyl esters of various dithiocarbamates were synthesized <2001L5621, 2000JFC181, 2000BMCL2779, 1998BCJ1973, 2001SL688>. By employing BrCH2CH(OEt)2 <1999SC3191, 1997S407> and several other alkyl halides <2001TL2055, 1997M881> in the alkylation step, the corresponding S-esters were obtained. Different kinds of dithiocarbamates have been prepared by a simple, one-pot procedure from primary or secondary amines, CS2, and a variety of alkyl halides in the presence of anhydrous K3PO4 under mild conditions in good yields <1998SC295>. In a number of cases, the alkylation of the dithiocarbamates, e.g., with an -halogenated ketone, was followed by cyclization to yield thiazole-2(3H)-thiones <2000JOC6069, 1998S1442>.

Functions Containing a Thiocarbonyl Group and at Least One Halogen

531

For the rapid synthesis of various thiadiazolylthiazol-2(3H)-thiones, a microwave-accelerated solid-state protocol has been described <2001SC817>. The preparation of the thiazolidinethiones from (1R,2S)-ephedrine or (1R*,2S*)-norephedrine was found to involve inversion of the configuration, as determined by X-ray analysis <1995JOC6604>. Employing different alkylating agents, further heterocycles containing the SC(S)N fragment have been synthesized: rhodamines with RCHBrCO2 <1997CHIR568> and thiazole derivatives with CH2ClCO2Et <2001MI269>. When the reaction of aromatic primary amines with CS2/Et3N was followed by treatment with aqueous hydrogen peroxide, the corresponding benzoxa(thia)zol-2-thiones were obtained <2000TL5833>.

(ii) From metal or ammonium dithiocarbamates The S-alkylation, S-arylation, or S-acylation of alkali metal or ammonium dithiocarbamates by alkyl halides and related compounds is another general synthetic method for the preparation of the S-esters of the dithiocarbamates (Scheme 31). S R2N C

S +

R'

S M

+

CH2 Cl

O R'

C

R2N C

SCH2R' S

R2N C

Cl

S C(O)R'

Scheme 31

New, substituted triazolyl dithiocarbanilates <1999MI15> and benzofuranyl dithiocarbamates <2001CHE1424, 1997PS411> have been synthesized using this methodology. N-hydroxy thiazole-2-thione, loaded on a Wang resin, was treated along similar lines and was successfully used as a supported reagent for a solid-phase version of the photochemical generation of radicals <2001OL855>. A polymer-supported diethyldithiocarbamate anion reacted with primary and secondary alcohols via their trifluoroacetates and produced alkylated dithiocarbamates in good yields <2000JCR(S)450>. Treatment of a terpene alcohol with zinc N,N-dimethyldithiocarbamic acid in the presence of triphenylphosphine and DEAD proceeded with inversion of the configuration at the carbon atom to provide the dithiocarbamate in 75% yield after chromatography <1999TA4129> (Equation (32)). R

R PPh3 DEAD Zn(SC(S)NMe2)2 toluene

HO

Me2N

S

ð32Þ

S

Allyldithiocarbamates (Me2NC(S)SCH¼CHAr) have been produced by the reaction of sodium dithiocarbamate with BrCH2Ph3P+Br. The intermediate, Me2NC(S)SCH2Ph3P+Br, in the presence of t-BuOK underwent a Wittig reaction with aldehydes to form the allyl dithiocarbamates in good yields <1996SC509>. The aryliodonium salts proved to be very useful for the synthesis of S-aryl dithiocarbamates; nucleophilic attack of sodium dithiocarbamate afforded the sodium salt, after acidification of the corresponding dithiocarbamate <1995CC325, 1995SC1627> (Equation (33)). O H O

N N H

O

+

IPh

i. Et2NC(S)SNa

O

DMF rt ii. HCl

H O

S S C

N

NEt2 N H

O

Polymer-supported diaryliodonium salts have also been employed <2000JCR(S)352>.

ð33Þ

532

Functions Containing a Thiocarbonyl Group and at Least One Halogen

Alkali metal dithiocarbamates also readily react with alkenes, exhibiting both electrophilic and nucleophilic properties, to form the corresponding S-alkylated reaction products <2000MI1245> (the same as they do with 1-naphthyldiazonium salts to provide the 1-naphthyl-azophenyl dithiocarbamates <2001MI372>).

(iii) From isothiocyanates The addition of thiols to isothiocyanates yielded the N-monosubstituted esters of dithiocarbamic acid. Triethylamine was found to accelerate the reaction. Isothiocyanates and -thiobutyrolactone, when gently heated with NaOH in a dioxane/water system and followed by acidification, yielded the 4-thiocarbamoylthiobutyric acids <1999JHC1167>, which can be easily cyclized to the seven-membered 2-thioxo-1,3-thiazepan-4-ones (Equation (34)). O i. NaOH

R N C S + S

O

R

S

R

O

ð34Þ

N

N C

ii. HCl

H

S

OH

S

S

The nucleophilic addition of NaHS to hexa-2,4-dienoyl isothiocyanate afforded the cyclized 6-(propen-1-yl)-2-thioxotetrahydro-4H-1,4-thiazin-4-one <1999MI260> (Equation (35)). O

C NCS

O

NaSH i. MeOH

NH

ð35Þ

ii. Acetone S

S

The corresponding benzothiazine-2-thione hetereocycle was prepared by intramolecular heteroconjugate addition of isocyanates promoted by the CS2/TBAF system <2000TL4895>. Similarly, starting from isothiocyanates, -D-(glucopyranosyl)-tetrahydro-2-thioxo-4H-1,3-thiazin-4-ones <1995LA2231> and thiazole-2-3H-thiones <1997PHA750> were prepared.

(iv) From thiuram disulfides Anions of enolized heteroaromatic 1,3-dicarbonyl systems reacted with tetraalkylthiuram disulfides, which in the reaction system DMF/K2CO3 were sufficiently electrophilic to produce the heterocyclic dithiocarbamates in good yields <1999M1147, 2000JHC911, 2000SUL287>. Treatment of the doubly lithiated 2-(pivaloylamino)pyridine with tetraisopropylthiuram disulfide gave rise to the 3-diisopropyldithiocarbamato derivative in high yield (Scheme 32). OH

OH

O

(R2N-C(S)S)2

NH CO t Bu

NR2

O

i. BuLi ii. (i-Pr2NC(S)S)2 N

S S C

DMF/K2CO3

iii. HCl 73%

S C N

S Ni-Pr2

NH CO t-Bu

Scheme 32

The tetraethylthiuram disulfides also reacted under different reaction conditions with perfluoroorgano silver(I) and perfluoroorgano cadmium compounds to provide the corresponding perfluoroorgano esters of diethyldithiocarbamic acid and metal diethyldithiocarbamates MSC(S)NEt2 (M = Ag or Cd/2), the latter product precipitating immediately in THF <2001ZAAC1264> (Equation (36)).

Functions Containing a Thiocarbonyl Group and at Least One Halogen S Et2N C

+

XRf

S 2

S

THF –30 °C

Et2N C

S

+

X S

SRf

533

C NEt2

ð36Þ

X = Ag, Cd/2

(v) Other methods Metal diethyl dithiocarbamates and their N-methyl quarternary salts have been shown to be efficient methyldithiocarbonyl transfer reagents for the syntheses of dithiocarbamates <2000T629> (Scheme 33). S N C SMe

N

S

R2NH

Me N

R2N C

EtOH/∆

S N C SMe

SMe

I

Scheme 33

The yields for a number of aliphatic/aromatic primary and secondary amines were high, 70–85% (except for R = t-Bu), thus providing a facile route to methyldithiocarbamates from nonhazardous starting materials. The chemistry of both tri- and pentavalent compounds of As, Sb, and Bi from xanthate- and dithiocarbamate-based ligands has been reviewed <2003CCR35>. Both arylalkylidene rhodanine <2000TL5729> and methyldithiocarbonyl transfer reagent for use in solid-phase combinatorial synthesis (Equation (37)).

O

O C

H N O

S N

S O

S S

N

ð37Þ

S

O

(vi) N-acyl-1,3-thiazolidine-2-thiones as auxiliary agents N-acyl-1,3-thiazolidine-2-thiones have been employed in auxiliary-based highly diastereoselective aldol additions. For the enolization, TiCl4/()-sparteine <2000OL775> and TiCl4/N-ethylpyrrolidine/CH2Cl2 <1996TL8949, 2000OL2151> followed by an aldehyde were employed. Diastereoselectivities greater than 90:10 were obtained (Equation (38)). S

O N

S

TiCl4 /amine

R

N

S

OH O

S

OH O

S

+

R

N

S

ð38Þ

R CHO >50% >90:10

The influence of several Lewis acids on the stereoselectivity and overall yield has been examined <2001TL4629>; the best diastereoselectivity was obtained when using SnCl4. The same high diastereoselectivity was achieved for the Lewis acid-mediated cross-coupling reaction of dimethylacetals (up to 98:2) <2001OL615>.

534 6.17.2.4.3

Functions Containing a Thiocarbonyl Group and at Least One Halogen Bis-[thiocarbamoyl](thiuram)disulfides

Bis(thiocarbamoyl)disulfides were obtained by oxidation of the salts of dithiocarbamic acid (not always isolated). A wide range of oxidation reagents have been used, from chlorine to ammonium persulfate <1983HOU(E4)408> (COFGT (1995)). A new, attractive method under mild conditions has been reported for obtaining the tetraalkylthiuram disulfides (R = Me, Et, i-Pr, cyclohexyl, CH2CH2OH). Dialkyldithiocarbamic acid or the sodium salt were subjected to sodium chlorite, and the tetraalkylthiuram disulfides were obtained instantaneously, pure and in very high yields <1995SC227> (Equation (39)). S

NaClO2/H2O

R2N C

0–5 °C, 20 min

SH

S S R2N C

C NR2

ð39Þ

S S

73–93%

Tetrabutylthiuram disulfide and bis[(3-methoxycarbonyl-5-methyl-pyrazol)-1-yl thiocarbonyl] disulfide were prepared by dissolving the appropriate amine in ethanol, adding CS2 to the cooled solution followed by the addition of solid iodine. Yields ranged from 83% to 90% <2001MI232, 2001MI234>.

6.17.2.5

Trithiocarbonates (Esters of Trithiocarbonic Acid)

Trithiocarbonic acid has been isolated as a reddish liquid at room temperature (m.p. –26.9 C) but is unstable and decomposes into CS2 and H2S. At 78 C though, it can be stored for extended periods of time. The salts of trithiocarbonic acid are more stable and rather easily available. With the exclusion of moisture, they can be stored without decomposition <1983HOU(E4)408>.

6.17.2.5.1

Salts of monoesters of trithiocarbonic acid

The blood-red trithiocarbonate anion S¼CS22 has been prepared by treating ammonium sulfide, strong aqueous ammonia, alkali metal sulfides, or aqueous alkali metal hydroxide with CS2 <1983HOU(E4)408, COFGT-II>. To promote the reaction, a phase-transfer catalyst or an anion-exchange resin has often been used <1998JCR(S)454>. The reaction of aliphatic and aromatic thiolates with polarized CS2 leads to the formation of the salts of the monoesters of trithiocarbonic acids, e.g., the stable triethylbenzylammonium (TEBA) salts of the corresponding trithiocarbonic acid <1996JCR(S)64> (Equation (40)). +

N

6.17.2.5.2

N CH2 CN

TEBA Cl – CS2/OH

–

CN N CH N C S + – TEBA S

S CS2

S +

TEBA

ð40Þ

S +

TEBA

Diesters of trithiocarbonic acid

(i) From thiophosgene or xanthates The diesters of trithiocarbonic acid have been produced from thiophosgene and thiols, thiophenols, or their salts. The dithiols <1997PS413, 2000PS153> and dithiolates as well as disilanylsulfanyl derivatives <2001T5739> produced cyclic trithiocarbonic esters. In the case of the disilanylsulfanyl derivatives, the reaction yields were shown to improve considerably if phenyl chlorothionoformate PhOC(S)Cl was used instead of thiophosgene. The 1,3-dithiol-2-thione derivatives were also obtainable as cyclization products of the RSC(S)Oi-Pr derivatives, which were synthesized from pyridyl acyl bromide and NaSC(S)Oi-Pr <2001TL1571> (Scheme 34).

Functions Containing a Thiocarbonyl Group and at Least One Halogen N

C

P4S10

S O

CO CH2 S C

N

H2O 45% N

N

C

70 °C

Oi-Pr

S

70%

S

H2SO4, 50 °C

S

NaSC(S)Oi-Pr

COCH2Br

535

S S

Scheme 34

(ii) From carbon disulfide Symmetrical trithiocarbonates were obtained directly and in excellent yields by the reaction of primary or secondary alkyl, benzyl, or allyl halides with KOH and CS2 in anhydrous THF <1995JCR(S)478, 1996JCR(S)64> (Equations (41) and (42)). S 2 RX

CS2, KOH, THF

R S

S R

ð41Þ

60–90% X = Hal Me

Me NC HS

CN N Ph

CS2/ TEA, Pb(ac)2

NC O

O

Me CN NC S

N Ph

S

S

CN

ð42Þ N Ph

O

The corresponding bis(azinyl)trithiocarbonates were synthesized from the corresponding pyridone thiol using the same methodology but by using CS2 in the presence of triethylamine and Pb(II)Ac2 <1995H2195>. In the presence of an anion-exchange resin in the hydroxy form, primary, secondary, allylic, and benzylic halides were converted, by the reaction with CS2 under mild reaction conditions, exclusively into the corresponding dialkyl trithiocarbonates. They were obtained as virtually pure products (according to 1 H NMR) in excellent yields (>90%) and in considerably shorter reaction times <1998JCR(S)454>. The synthesis of the 1,3-dithiol-2-thione-4,5-dithiolate anion employing the carbon disulfide route (CS2/Na/DMF) has been reviewed in 1995 <1995PS145>. A convenient, one-pot preparation of 1,3-dithiol-2-thiones and 1,3-diselenol-2-selenones, substituted with phenyl, alkyl, alkylthio, hydroxymethyl, or formyl groups, from readily available acetylenes and CS2 has been reported in good-to-excellent yields <1997SL319> (Equation (43)). i. n-BuLi/ THF ii. X R C CH

iii. CX2

X

R

X

H

X

ð43Þ

>75% X = S, Se; R = H, Ph, SMe, n-Hex, CH(OEt)2

Tetramethylethylenediamine was usually found to be effective for enhancing the yields, especially for the selenium compounds.

(iii) From the salts of trithiocarbonic acid or monoesters Vinyl esters of trithiocarbonic acids have been stereoselectively prepared by the reaction of potassium S-alkyl(aryl) trithiocarbonates with vinyl(phenyl)iodonium tetrafluoroborate <2000SC3897> (Equation (44)).

536

Functions Containing a Thiocarbonyl Group and at Least One Halogen S S R'CH CHI

+

RS C

+

THF

– PhBF4

R' CH CH S

rt >60%

SK

SR

ð44Þ

R = Et, PhCH2, Ph; R' = Ph, n-Bu

In the case of R1 = Ph, retention of the configuration was observed. However, in the case of R1 = n-Bu, complete inversion of the configuration was obtained, the reaction probably proceeding via an SN2-type reaction mechanism.

(iv) From bisalkoxythiocarbonyl disulfides The 1,3-dithiol-2-thione ring was also prepared in a one-pot reaction from bis(diisopropyloxythiocarbonyl) disulfide and various alkynes under radical conditions, the five-membered heterocycle being formed via the ring closure of a vinyl radical <1998H2003> (Equation (45)). R

(i-PrS-C(S)-S)2

R'

S

S

AIBN >40%

S

R

ð45Þ

R'

R, R' = aryl, alkyl

The reaction was optimal for alkynes conjugated with a C¼C double bond.

(v) Other methods The reaction of stannylenes with an excess of CS2 resulted in the formation of a chrome-yellow asymmetric alkene, the structure of which was established by X-ray diffraction <1995OM3620> (Scheme 35). S

Tbt

i. CS 2(5 equiv.)

Sn : Tip

Tbt Sn

–70 °C

S

S

Tip

C C S

S S Sn Tbt Tip

R R

R = CH(SiMe3)2(Tbt) i-Pr(Tip)

R

Scheme 35

The strain inherent in the thietene ring serves as the driving force for its expansion via breakage of the weak CS bond under mild conditions. The ring expansion using CS2/THF was catalyzed by alkali metal halides and afforded the corresponding six-membered dithiocarbonates in high yields <2002IJC1234>. The products were obtained as racemates (Equation (46)). Ar S

S

N S

CS2/ THF Ar

rt

Ar S

S

N

S S

S

ð46Þ

Ar

Two types of naphtho-fused 1,3-dithiol-2-thiones have been synthesized by the reaction of 3,4,7,8-tetrachloronaphtho[1,8-cd:5,6-c0 d0 ]bis(1,2-dithiol) with sodium trithiocarbonate <1998EJO1577> (Equation (47)).

537

Functions Containing a Thiocarbonyl Group and at Least One Halogen S S Cl

Cl

Cl

Cl S

S

SR

S i. Na2S2C S ii. R–X

Cl

S

S

Cl S

S

ð47Þ

SR

S R = alkyl, benzyl

(vi) The organic chemistry of 1,3-dithiol-2-thione 1,3-Dithiol-2-thione, after lithiation with LDA, reacted with aryl carbaldehydes to afford the bisalcohol products in excellent yields. <2001CC369> (Equation (48)). Ar S

LDA Aryl–CHO

S S

S

OH OH

S S

ð48Þ

Ar

The diols were observed to slowly decompose at ambient temperature. Dihydro-1,3-dithiol-2-thione was converted into a polycyclic sulfonium salt by reaction with acetylenes <2000HAC434> or benzyne (generated by the thermolysis of 2 equiv. of 2-carboxybenzenediazonium chloride) <1999H103> (Equation (49)). COOMe

S S

S DMAD

+

MeOOC

S

–

S

S COOMe

ð49Þ

+

MeOOC

COOMe

COOMe

In the first case, the short-lived ylide was trapped; in the second case, the sulfonium salt was isolated in good yield and was utilized as the starting material for the synthesis of a number of macrocylic rings of various ring size. Direct cycloaddition of C60 to a diene, formed in situ by the thermal extrusion of SO2 from the corresponding 1,3-dithiol-2-thione derivative, yielded the cycloadduct in 61% yield <1998JOC5201> (Equation (50)). C60

S +

O2S

S S

Chlorobenzene ∆

S C60

S

ð50Þ

S

The C60 adduct was obtained as an inclusion compound of CS2, the application of heat under high vacuum gave the solvent-free thione.

(vii) Synthesis and chemistry of 1,3-dithiol-2-thione-4,5-dithiolates and their zinc complexes 1,3-Dithiol-2-thione-4,5-dithiolates, their zinc complexes, and other derivatives are useful starting materials for the preparation of -donor molecules, precursors of organic conductors, and superconductors. Methods for their preparation prior to 1995 have been reviewed <1995S215>. An alternative method for the preparation of 1,3-dithiol-2-thione-4,5-dithiolate, the zinc complex, and 4,5-ethylenedithio-1,3-dithiol-2-thione has been published <2000ZN231> (Scheme 36). In the presence of a dienophile, the latter undergoes Diels–Alder-type pericyclic reactions <2000ZN231, 2001MI749, 1999TL8819>. 4,5-Ethylenedithio-1,3-dithiol-2-thione was readily alkylated using 2-chloroethanol [or 3-bromopropanols, 2-(2-chloroethoxy)ethanol, etc.]

538

Functions Containing a Thiocarbonyl Group and at Least One Halogen

CS2

Na/DMF 0 °C 95–100%

NaS

S

H+

S

R1

S

S

R2

S

S

S +

S NaS

R1

S

S

S

S

S R2

Zn eO ,M 2 Cl Br N 4 Bu H S

S

S

S

S

(Bu4N)2 Zn

2

Scheme 36

<2000S1615>, benzoyl chloride <1998S1615>, or 2-chloro-2-phenylacetophenone <2000CC2039> to form symmetric, dialkylation products. The monoalkylated product 4-alkylthio-1,3-dithiol2-thione was obtained from the zinc complex of 1,3-dithiol-2-thione-4,5-dithiolate using electrophilic reagents in the presence of 3-picolylchloride hydrochloride or 4-picolyl chloride hydrochloride or pyridine hydrochloride <2001OL1941>. The treatment of the 4,5-diphenacyl-1,3-dithiol-2-thiones obtained in this manner with Lawsson’s reagent in refluxing toluene led to the formation of six-membered heterocycles when R was Ph or 4-NO2Ph, and to the fused thiophene derivative when R was 4-MeOPh <1996TL2821>. Similarly, the condensation of dicesium 2-thioxo-1,3-thiol-4,5-diselenolate with bisalkylating polythioethers in high dilution leads to a number of thiaselena crown compounds <1996LCS(P1)1995>. The neutral 1,3-dithiol-2-thione-4,5-dithiolate complexes with organic antimony <2001IC2570> and ruthenium (NO, cyclopentendienyl) <1995ICA57>, ruthenium (¼O) <2001EJI1625>, dinuclear bis[dicarbonyl(cyclopentadienyl)]diiron(II) <2002JOM94>, cadmium <2000JA11007>, and palladium complexes <2002JCS(D)1377>, have been synthesized and characterized by X-ray diffraction.

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2000T5413 2000T5819 2000T7173 2000TL4895 2000TL5729 2000TL5833 2000TL9815 2000ZN231 2001BMCL1609 2001CAR123 2001CC369 2001CC2618 2001CHE1424 2001CL103 2001CPB361 2001EJI1625 2001H279 2001H301 2001IC2570 2001JA4717 2001JA5602 2001JIC372 2001JOC894 2001JOC1061 2001JOC2104 2001JOC3940 2001JOC8935 2001L5621 2001MI232 2001MI234 2001MI269 2001MI365 2001MI372 2001MI749 2001OL615 2001OL855 2001OL1069 2001OL1941 2001OL2141 2001S1965 2001SC817 2001SL625 2001SL688 2001T3175 2001T3567 2001T5739 2001TL859 2001TL1571 2001TL2055 2001TL2977 2001TL4629 2001TL5085 2001TL5413

Functions Containing a Thiocarbonyl Group and at Least One Halogen 2001TL7091 2001TL8625 2001ZAAC1264 2002CAR397 2002CEJ1856 2002CL1879 2002HAC280 2002ICA71 2002IJC1234 2002IJC(B)1510 2002JCS(D)1377 2002JOC6896 2002JOM94 2002MI13 2002OL2253 2002T2339 2002T2831 2002TA759 2002TL2801 2003CCR35 2003JPC(A)4697

543

C. L. Winn, J. M. Goodman, Tetrahedron Lett. 2001, 42, 7091–7093. P. Meffre, R. H. Dave, J. Leroy, B. Badet, Tetrahedron Lett. 2001, 42, 8625–8627. W. Wessel, W. Tyrra, D. Naumann, Z. Anorg. Allg. Chem. 2001, 627, 1264–1268. Y. Chong, C. K. Chu, Carbohydr. Res. 2002, 337, 397–402. A. Fu¨rstner, F. Stelzer, A. Rumbo, H. Krause, Chem. Eur. J. 2002, 8, 1856–1871. M. Lautens, J. T. Colucci, S. Hiebert, N. D. Smith, G. Bouchain, Org. Lett. 2002, 4, 1879–1882. E. Kh. Ahmed, Heteroatom Chem. 2002, 13, 280. J. S. Casas, E. E. Castello, J. Ellena, I. Haiduc, A. Sanchez, R. F. Semeniuc, J. Sordo, Inorg. Chim. Acta 2002, 329, 71–78. L. D. S. Yadav, S. Dubey, S. Singh, Indian J. Chem., Sect. B 2002, 41B, 1234–1237. H. Yin, Y. Wang, R. Zhang, C. Ma, Indian J. Chem., Sect. B 2002, 41B, 1510–1512. F. Qui, T. C. W. Mak, Z. Z. Yuan, Y. Qing-Chuan, L. Zhi, Y. Wen-Tao, Z. Dao-Ben, J. Min-Hua, J. Chem. Soc., Dalton Trans. 2002, 1377–1385. R. Martin, M. Alcon, M. A. Pericas, A. Riera, J. Org. Chem. 2002, 67, 6896–6901. G.-E. Marsubayashi, T. Ryowa, H. Tamura, M. Nakano, R. Arakawa, J. Organomet. Chem. 2002, 645, 94–100. X. Song, C. Cahill, G. Eng, Main Group Metal Chem. 2002, 25, 13–14. N. R. Guz, A. J. Phillips, Org. Lett. 2002, 4, 2253–2256. M. Goto, I. Miyoshi, Y. Ishii, Y. Ogasawara, Y.-I. Kakimoto, S. Naguma, A. Nishida, N. Kawahara, M. Nishida, Tetrahedron 2002, 58, 2339–2350. D. J. Clarke, S. Eoss, Tetrahedron 2002, 58, 2831–2837. P. Camps, G. Colet, M. Font-Bardia, V. Munoz-Torrero, X. Solans, S. Vazquez, Tetrahedron Asymm. 2002, 13, 759–778. S. Kim, J. A. Lawson, D. Pratico, G. A. FitzGerald, J. Rokach, Tetrahedron Lett. 2002, 43, 2801–2805. S. S. Garje, V. K. Jain, Coord. Chem. Rev. 2003, 236, 35–56. T. H. Johansen, K. Hagen, J. Phys. Chem. A 2003, 107, 4697–4706.

544

Functions Containing a Thiocarbonyl Group and at Least One Halogen Biographical sketch

Professor Erich Kleinpeter obtained his diploma from the University of Leipzig, Germany in 1970 and his Dr. rer. nat. in 1974 under the direction of Professor Rolf Borsdorf. He continued teaching and research work at the University of Leipzig until 1979, when he spent a year in the laboratories of Professor Rainer Radeglia at the Academy of Sciences, Berlin. Following this, he returned to Leipzig and habilitated in 1981. After spending 1982–1985 as Associate Professor of Organic Chemistry at the University of Addis Ababa, Ethiopia, he moved to the University of Halle-Wittenberg, Germany, where he was appointed a docent in spectroscopy, followed later by his appointment as Professor of Analytical Chemistry in 1988. In 1993 he took up his present position as full Professor of Analytical Chemistry at the University of Potsdam, Germany. His research interests include all aspects of physical organic chemistry, in particular the application of NMR spectroscopy, quantum chemical calculations, and mass spectrometry to the examination and investigation of all kinds of interesting structures and new phenomena in organic, bioorganic, and coordination chemistry.

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 495–544

6.18 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Other Than a Halogen or Chalcogen J. BARLUENGA, E. RUBIO, and M. TOMA´S Universidad de Oviedo, Oviedo, Spain 6.18.1 THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 6.18.1.1 Thiocarbonyl Derivatives with Two Nitrogen Functions 6.18.1.1.1 From isothiocyanates 6.18.1.1.2 From carbon disulfide 6.18.1.1.3 From thiophosgene 6.18.1.1.4 From thiocarbonyl transfer reagents 6.18.1.1.5 From ureas 6.18.1.1.6 Miscellaneous methods 6.18.1.1.7 From thiocyanate salts and alkyl thiocyanates 6.18.1.1.8 From thiocarbamoyl transfer reagents 6.18.1.1.9 From sulfur-transfer reagents 6.18.1.2 Thiocarbonyl Derivatives with One Nitrogen and One Phosphorus Function 6.18.1.2.1 From isothiocyanates 6.18.1.2.2 From halothioamides 6.18.1.2.3 From thiophosphinoyldithioformates 6.18.1.2.4 From phosphonodithioformates 6.18.1.2.5 Miscellaneous methods 6.18.2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION 6.18.2.1 Thiocarbonyl Derivatives with Two Silicon Functions 6.18.2.2 Thiocarbonyl Derivatives with Two Phosphorus Functions

6.18.1

545 545 545 553 555 555 556 556 557 559 561 564 564 566 567 567 567 568 568 568

THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS)

6.18.1.1 6.18.1.1.1

Thiocarbonyl Derivatives with Two Nitrogen Functions From isothiocyanates

The addition reaction of amines to isothiocyanates still continues to be the most general access to a wide array of thiourea derivatives (Equation (1)). In this section, some recent results concerning new improvements as well as the application in the synthesis of molecules of interest are highlighted. 545

546

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms R1 N C S

H N

+ R2

S R3

35–100%

R1HN

NR2R3

ð1Þ

R1

= alkyl, aryl R2, R3 = H, alkyl, aryl

Recently, Fuentes and co-workers <2002JOC2577> have reported the synthesis of thioureylene di-C-nucleosides, a new type of dinucleotide analog, based on the addition of amines to isothiocyanates (Scheme 1). Thus, the reaction of 30 -amino-C-nucleosides with 30 -isothiocyanatoC-nucleosides, which are in turn formed by reaction of the corresponding amine nucleosides with thiocarbonyldiimidazole (TCDI), produces thioureylene di-C-nucleosides in very high to quantitative yields. S NH2

R1

O

SCN

R2

O

+ OAc

OAc

DMF or acetone

HN

NH

R1

40 °C 80–100%

O

O

R2

OAc

OAc

R1, R2 = furan, imidazoline-2-thione, pyrrole derivatives

Scheme 1

In a study focused on nonbiarylatropoisomers derived from carbohydrates, Palacios and co-workers <1999T4377> have described a facile access to chiral cyclic thioureas, specifically 2-aryl-5-hydroxyimidazolidine-2-thiones, in moderate yields via addition of D-glucosamine to aryl isothiocyanates (aryl = 2-FC6H4, 2-ClC6H4, 2-BrC6H4) (Scheme 2). A related reaction involving D-fructosamines with different sugar isothiocyanates has been released <2000TA435>.

S OH

HO HO

EtOH–H2O

O

+

ArN=C=S 45 °C 65–76%

OH NH2

Ar N HO HO

NH H OH OH CH2OH

Ar = 2-X-C6H4; X = F, Cl, Br

Scheme 2

A high-yielding synthesis of guanidium derivatives from ethyl carbamate protected thioureas was reported. The latter were in turn prepared by addition of amines to ethyl thiocyanato formate <2002TL565>. Some modern techniques have been incorporated for the synthesis of the thiourea functional group in order to overcome inherent difficulties found in the traditional methods. For instance, fluorous electrophilic scavengers for solution-phase synthesis have been successfully tested (Scheme 3) <2003TL2065>. Thus, fluorous isatoic anhydride 1 and isocyanate 2 are used as scavengers for amines in solution-phase synthesis of thioureas from isothiocyanates and excess of primary and secondary amines. The fluorous derivatives thus formed are readily separated from the reaction mixture by solid-phase extraction (SPE) over fluorous silica. The yields are in general high, particularly with the fluorous scavenger 1, and the purity greater than 95% after the scavenging operation.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms S

i. R1R2NH (1.5 equiv.)/CH2Cl2 PhNCS ii. 1 or 2 (1.0 equiv.)/SPE

72–100% (from 1) NR1R2

PhHN

547

1 = alkyl,

R

34–98% (from 2)

H

R2 = alkyl C8F17

N O

O

C8F17

O 1

NCO 2

Scheme 3

In addition, solid-state reactions have also become promising in the thiourea system synthesis. Thus, Kaupp and co-workers <2000T6899> have reported a series of solid-state reactions between solid or gaseous amines and solid isothiocyanates to produce substituted thioureas in quantitative yields (100% yield, 53 examples) (Scheme 4). Except for washing in a few cases, the reaction does not require work-up, and allows for upscaling to the kilogram scale. S

R2R3NH R1NCS

R1HN

–30 °C to rt

NR2R3

R1 = Ar, Me R2 = Ar, Me, H R3 = Me, H

solid state 100 %

Scheme 4

The high-pressure technique has been applied in the preparation of a number of thioureas derived from aryl- and cyclohexyl-substituted isothiocyanates and different amino-substituted pyridines and diazines (Scheme 5) <2002TL1035>. The yield of the high-pressure reaction is significantly higher (67%) than that of the thermal reaction (29% along with 38% of N,N0 -diphenylthiourea) as it was found for the model components 4-aminopyridine and phenyl isothiocyanate. H N

NH2 +

N

PhNCS S

N

THF, reflux

NHPh

THF, 40 °C, 0.6 GPa

29% 67%

NH2 N H 2N

N

H2N

N

NH2

N

N

N

N NH2

N

NH2

THF, 40–80 °C 0.6 GPa 47–95%

4-MeO-C6H4-NCS

4-Me2N-C6H4-N=N

NCS

c-C6H11-NCS

Scheme 5

Cyclic thioureas, particularly thiohydantoins, have attracted much attention mostly because of their biological properties. A practical eco-friendly procedure for the synthesis of 2-thiohydantoins and 5-alkylamino-2-thiohydantoins has been developed recently using the solvent-less

548

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

technique (Scheme 6) <2002TL8745>. Thus, the reaction of methylglycinate hydrochloride with isothiocyanates in refluxing diethyl ether or ethyl acetate gives rise to simple 2-thioxoimidazolidin-4-ones, which are in turn transformed into 5-aminomethylidene derivatives by treatment with dimethylformamide diethylacetal (DMF-DEA) under solventless microwave irradiation. Cl–

TEA

+

H3N

CO2Me

S

Et2O or EtOAc

+ reflux

R-NCS

R

H N

DMF–DEA no solvent

S

O

Microwave 70–80 °C

R

N

~96%

R = Me, Bu, Ph

H N

N

N O

74–77%

Scheme 6

Following this report, Dannhardt and co-workers have investigated the affinity to the glycine site of the NMDA receptor of different indole-2-carboxylic acids having a thiohydantoinmethyl substituent at C-3. The preparation of the target molecules involves reductive amination of ethyl 3-formylindole-2-carboxylate with various amino acid esters followed by cyclization with isothiocyanates and ester hydrolysis (Scheme 7) <2003JMC64>. i. H2NCHR1CO2Me

Cl

ii. R2NCS Et3N/∆

CHO

N

Cl

iii. LiOH

N H

O R1

CO2Et Cl

R2 N

S

Na(AcO)3BH

CO2H

N H

Cl

R1 = H, Me, Pri R2 = Et, aryl

Scheme 7

In the course of studies directed to the total synthesis of batzelladine alkaloids, Elliot and co-workers have reported a short access to substituted pyrrolo[1,2-c]pyrimidine-1-thiones (Scheme 8) <2002TL9191>. First, the necessary alkenyl pyrrolidine substrate is obtained from glutamic acid in five steps. Then, the key annulation step is based on the previous report by Kishi <1992JA7001> and is accomplished by the three-component reaction of alkenyl pyrrolidine, silicon tetraisothiocyanate, and acetaldehyde at room temperature. Si(NCS)4 benzene CH3CHO

TBSO NH2 HO2C

NH CO2H

CO2Et

rt

S

TBSO N

S

TBSO NH

+

Me CO2Et 54%

N

NH Me CO2Et 27%

Batzelladine A

Scheme 8

The group of Ortiz Mellet and Garcı´ a Ferna´ndez have elegantly effected the preparation of cyclooligosaccharide receptors of different ring size featuring a hydrophobic cavity. The macrocyclic ring is constructed by double—inter and intramolecular—amine-to-isothiocyanate addition

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

549

(Scheme 9) <2002AG(E)3674>. Thus, the cyclodimerization of diisothiocyanate and diamino disaccharides can be effected in moderate yield by mild heating in pyridine. The cyclotrimerization product is obtained from the acyclic thiourea dimer containing two isothiocyanate moieties, which is directly available by homocoupling of the corresponding diisothiocyanate disaccharide (vide infra, Scheme 14). Thus, the addition of the diamine disaccharide to the diisothiocyanate substrate affords moderate to high yields of the final cyclic pseudohexasaccharide. SCN

NCS

Pyridine

+ H2N

40 °C

NH2

HN

NH

HN

NH

S

S

40% S H

Pyridine HN

NCS

HN

NCS

H2N

S

H N

N

NH2 40 °C 25–70%

43%

N H

H N S

N H

N H

S

O RO OR =

OR RO

OR

R = OAc, TMS, H

OR

Scheme 9

The preparation of thiourea-functionalized resorcinarene cavitands, a novel class of neutral anion receptors, is also feasible starting from either isothiocyanate- or amine-containing cavitands (Scheme 10) <1998JOC4174>. Thus, the reaction of the tetrakis[aminomethyl]cavitands with alkyl and aryl isothiocyanates R2-NCS allows one to isolate the corresponding tetrakis[thioureamethyl]cavitands in 27–63% yield. Conversely, a new cavitand is obtained in two steps and moderate overall yield by conversion of the aminocavitand into the isothiocyanate derivative followed by addition of the primary amine R3-NH2. The use of macrocyclic thioureas as efficient anion receptors has been extended to a variety of cyclophane-based structures. In this sense, different types of systems such as ortho–meta, meta– meta, and meta–para cyclophanes have been synthesized (Scheme 11) <2000JOC275>. The required starting materials are the 1,3-[bis(aminomethyl)]-4-,6-di-t-butylbenzene and the corresponding o-, m-, and p-bis(isothiocyanatomethyl)benzenes. The macrocyclization takes place in low-to-high yields by heating at 60 C in chloroform under high dilution conditions. Other examples using thiourea receptors with a rigid xanthene spacer have been reported <1997T1647>. In addition, a series of fluorescent naphthylthioureas containing hydroxymethyl groups have been synthesized from naphthyl isothiocyanates and -hydroxyamines <2003TL795>. A new macrocyclic system containing oligoethyleneglycol chain and thiourea moieties has been prepared and their binding ability toward dihydrogenphosphate anion and several cations investigated (Scheme 12) <2003TL8183>. The synthesis of the target molecule involves the reaction of the tetraazathiapentalene derivative, prepared from the bis(pyrimidine-2-thione) and methyl isothiocyanate, with the corresponding diisothiocyanate followed by heating with base. A number of thiourea-based compounds have been found to display an array of biological properties. Since thioureas are known to raise the HDL cholesterol, some functionalized systems with a thiourea moiety embedded in a functionalized side chain, for instance those having a -carboxylic acid group, have been prepared (Scheme 13) <2002BMC2439>. Thus, the addition of acyclic N,N-bis(trimethylsilyl)--amino acid esters or cyclic -amino acid esters to aromatic isothiocyanates in methanol provides the corresponding N-thiocarbamoyl--amino acid esters in moderate-to-high yields.

550

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

NH2 O

CH2Cl2/CHCl3/THF

O

S

H N

R2NCS

NHR2

O

O

rt to reflux 27–63% C5H11

4

C5H11 R2 = aryl,

54%

Cl2CS

H N

R3NH2

NCS

CH2Cl2 O

O

O

4

t-octyl

S NHR3 O

rt to reflux 55% C5H11

C5H11

4

4

NO2 O 4

R3 =

Scheme 10

S t-Bu

t-Bu

S

N H

N H

H N

H N

t-Bu OBu OBu t-Bu

S

N H

N H

OBu

H N

H N

OBu

t-Bu

t-Bu

S 70%

79%

CHCl3, high dilution, 60 °C

S

t-Bu

OBu

OBu

OBu or

or

OBu SCN

H N

OBu

SCN

OBu

NH2

H N

SCN

and t-Bu

N H

S 31%

SCN

NH2

N H

BuO SCN

OBu

NCS

Scheme 11

Additional examples of biologically active thioureas derived from isoquinolines, pyrrolidines, and aryl ethylamines have been reported recently. Among them, thioureas with antispasmodic activity <2001MI129> as well as thioureas with antagonist effect on a vanilloid receptor are worth noting <2003BMC197, 2003BMC601>. On the other hand, isothiocyanates can be readily transformed into the corresponding symmetric N,N0 -disubstituted thioureas upon treatment with pyridine water. The reaction is very well suited for those cases where the required amines are not accessible. The amine-free mechanism very likely involves thiocarbamic anhydrides as reactive intermediates (Scheme 14) <1999S1907>. This practical procedure has been applied by the authors not only to the synthesis of simple and carbohydrate-derived thioisocyanates, but also to more complex systems like cyclotetrahalins via macrocyclization of the corresponding oligosaccharide isothiocyanates (Scheme 14) <2002AG(E)3674>.

551

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Me N

S N

S

Me N

S

But

i, ii

S

N

N

Me N

But

N Me

N S

S

i. 3,6,9-Trioxaundecane-1,11-diisothiocyanate benzene, reflux, 56% ii. aq., KOH, EtOH, reflux, 69%

S

HN

O

HN O

=

HN O

HN

S

Scheme 12 ArNCS MeOH

CO2Et

(Me3Si)2N

R N H

N H

rt 44–95%

R

R

S Ar

R

CO2Et

R = Me R,R = –(CH2)3,5– Ar = 2X-5Y-C6H3 (X = Me, MeO; Y = Me, Cl) ArNCS CH2Cl2

HN

S Ar

CO2Et

N H

rt 77%

N

CO2Et

Ar = 2-Me-5-Cl-C6H3

Scheme 13 Pyridine/H2O (10:1) RNCS

S R

rt to 60 °C 72–95%

N H

N H

H 2O

–O C S RNCS

S R

SCN

NCS

R

R N H

H N

OH

Pyridine/H2O (15:1) 40 °C

S

HN

NCS

S HN

H N

O

NCS

R

S

Pyridine/H2O (10:1) 60 °C 38% overall

=

O RO

OR

O RO OR O OR OR

Scheme 14

HN

NH

HN

NH

S

S

552

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

During the last years some attention has been paid to the solid-phase synthesis of thioureas. For instance, the traceless synthesis of thioureas reported by Sim begins with the amination of the bromo-Wang resin followed by the addition of isothiocyanates. The thiourea unit was liberated from the resulting resin-bound thiourea by treatment with 50% TFA in CH2Cl2 (Scheme 15) <2001SL697>. While the overall yields are high, the observed purity is rather low (13–51%). An analogous synthesis of isoxazoline thioureas using the chloro-Wang resin is also known <2000TL5069>.

S R1NH2

Br

R2NCS

NH R1

CH2Cl2 rt

N R1

CH2Cl2 rt

N H

R2

S TFA-CH2Cl2 (1:1)

R1

N H

rt

N H

R1 = Prn

R2

R2 = aryl

68–92%

Scheme 15

Thiohydantoins are in turn available by solid-phase synthesis via polymer-supported amines as depicted in Scheme 16. Thus, the sodium polystyrylsulfinate reacts with 2-choloroethanol to give a polystyrylethanol resin which is coupled with protected glycine to afford, after deprotection, the corresponding resin-bound -amino acid. The latter is added to phenyl isothiocyanate and the resulting thiourea subjected to basic or acid treatment to provide acyclic and cyclic thioureas, respectively <2001TL1973>.

i. Cl SO2Na

OH

Bu4NI

S O2

ii. BOC-gly DCC iii. HCl

O

S 4 N NaOH dioxane

PhNCS DMF 90 °C

S S O2

NH2 O

O O

N H

HO2C

N H

N H

Ph

21% overall N H

Ph O 6 N HCl dioxane 20% overall

Ph N S N H

Scheme 16

Using a similar strategy, a high-yielding microwave-assisted synthesis of substituted thiohydantoins has been accomplished. In this process, Fmoc-protected -amino acids were coupled with HO-PEG-OH, deprotected, and reacted with isothiocyanates. After base-mediated cyclization, the thiohydantoin system was liberated from the matrix under microwave exposure <2003TL8739>. The preparation of substituted isoxazolethiohydantoins has also been reported from hydroxypropyloxymethylpolystyrene, alkynyl glycine, and isothiocyanates <1999JOC9297>. Moreover, it has been released an efficient solid-phase synthesis of quinazoline-2-thioxo-4-ones using SynPhaseTM lanterns supports <2000TL8333>.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

553

The solid-phase addition of triazenes to isothiocyanates has been designed as an efficient route to a new type of thioureas, which have been further elaborated into guanidines. The starting polymer-bound triazenes are prepared by addition of primary amines to the T2* diazonium resin <2000OL3563>.

6.18.1.1.2

From carbon disulfide

The dithiocarbamic acid unit represents a suitable thiocarbamoyl transfer agent (see Section 6.18.1.1.8). In most cases they are not commercially available and must be prepared. In this way, Tomkinson and co-workers <1998TL1673> have reported a simple, high-yielding procedure for the synthesis of thioureas in two steps from carbon disulfide, via amination of dithiocarbamic acids (Scheme 17). Thus, the reaction of primary or secondary aliphatic amines with carbon disulfide results in the formation of the corresponding dithiocarbamic acids, which then undergo amination upon treatment with primary or secondary 2,4-dinitrobenzenesulfonamides. This method thus provides access to symmetrical and unsymmetrical di-, tri-, and tetrasubstituted thioureas.

CS2 pyridine R1R2NH

CH2Cl2

R3R4NSO2Ar Cs2CO3 DMF, 80 °C

S R1R2N

SH

S R1R2N

–SO2 65–76%

NR3R4

R1 = Me, H (Ar = 2,4-dinitrophenyl)

R2 = Me, Bn, Ph R3 = 4-MeOC6H4-CH2 R4 = MeOCH2CH2, H

Scheme 17

Very recently, an efficient synthesis of unsymmetrical diaminocarbene ligands via reduction of unsymmetrical imidazolidine-2-thiones has been reported <2003AG(E)5243>. The methodology for the preparation of that type of cyclic thiourea was developed by Albrecht in 1994 by using lithium N-butyl-N-lithiomethyldithiocarbamates, readily available from N-methyl butylamine and carbon disulfide. The process consists of addition of the C-nucleophilic center of the dithiocarbamate to the imine followed by cyclization (Scheme 18) <1994S719>. R2

BuNHMe

i. BuLi ii. CS2 iii. BusLi

Bu S

S

NR1 N

Li SLi

R3 –78 to –10 °C 50–69%

Bu N

1 N R 2 R R3

R1 = H, Me, Pri, But R2 = H, Me, Et, Ph R3 = H, Me, Et, Pr, But, Ph R2, R3 = –(CH2)4, 5–

Scheme 18

The solid-phase synthesis has been accomplished by Mioskowski and co-workers <2000JCO75> by using a resin-bound dithiocarbamate moiety (Scheme 19). Thus, the treatment of the Merrifield resin with a primary amine in the presence of carbon disulfide produces the supported dithiocarbamate. Heating this dithiocarbamate in the presence of a

554

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

primary or secondary amine leads to the formation of the thiourea with the release of benzylthiol bound to resin. This method gives access to N,N0 -di- and trisubstituted thioureas in good yields and with 90% of purity in most cases. Cl

+ R1NH2

CS2 EtiPr2N

R2R3NH

NHR1

S

S + NR2R3

R1NH

Toluene 60 °C 33–97%

S

SH

R1 = alkyl, cycloalkyl, benzyl R2 = H, Me R3 = alkyl, benzyl R2, R3 = –(CH2)5–

Scheme 19

The synthesis of thioureas, as ‘‘en route’’ synthesis of modified chiral guanidines, has also been achieved by means of carbon disulfide itself as the thiocarbonyl source. Thus, Ishikawa and co-workers <2000JOC7774> have obtained a number of unsymmetrical thioureas resulting from sequential amination of CS2 with a primary amine—via the corresponding isothiocyanate—and an enantiopure diamine (Scheme 20). Application of this strategy to the synthesis of thioureido cyclodextrins by Ph3Pmediated coupling of CS2 (‘‘phosphinimine’’ approach) with cyclodextrin amines and primary amines has been executed by Marsuda and co-workers <1999TL6581, 2003TL1533>. i. R1NH2, Et3N CH2Cl2, rt CS2

R1HN

R2 ii.

R2

S N H

NH2 R2

NH2

H2N R2 CH2Cl2, rt 54–86%

R1 = alkyl, benzyl R2–R2 = Ph, Ph (S,S); (CH2)4 (R,R); (CH2)4 (S,S)

Scheme 20

Recently, the Italian group of Sartori, Ballini, and Maggi has carried out the carbon disulfidemediated synthesis of thioureas in the presence of heterogeneous and reusable catalysts. They have found that catalysts, such as Zn–Al HT(500) (a ZnO/Al2O3 composite) and MCM-41-TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene bound to mesoporous silica), are easily prepared and behave efficiently in the synthesis of acyclic and cyclic symmetrical thioureas (Scheme 21) <1999JOC1029, 2002TL8445>. RNH2 S RHN

90–100 °C NHR

cat.

NH2

H2N CS2

R = alkyl, benzyl, aryl Cat. = Zn-Al, HT (500) (100 °C, 57–100%) MCM-41-TBD (90 °C, 57–91%)

Scheme 21

90–100 °C cat.

S H N

N H

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms 6.18.1.1.3

555

From thiophosgene

Another traditional methodology based on thiophosgene is still being used. Thus, cyclic, optically active thioureas have been prepared and utilized as chiral guanidine precursors. In this way, the synthesis of 1,3-bis(phenylethyl)imidazoline-2-thione with C2-symmetry and bicyclic proline derived thiourea is shown in Scheme 22 <2000JOC7770>. Examples of application of this procedure to monosubstituted thioureas is reported in the synthesis of conformationally restricted L-arginine and L-homoarginine derivatives <1999JOC3467>.

CH3 Ph

H N

N H

N H

CH2Cl2, Et3N

CH3

H N O

CH3 S

CSCl2

Ph

Ph

N

CH3 N

Ph

rt, 84%

i. LiAlH4 THF, 60 °C

Ph

CH3 N

ii. CSCl2, Et3N

CH3

N Ph S

CH2Cl2, rt 47%

Scheme 22

6.18.1.1.4

From thiocarbonyl transfer reagents

The double amination of appropriately designed thiocarbonyl synthons is currently another useful synthetic route for building up the thiourea functionality. In this sense, 1-(methyldithiocarbonyl) imidazole 3 and its N-methyl quaternary salt 4 have become efficient thiocarbonyl transfer reagents for the synthesis of a diversity of thioureas (Scheme 23) <2000T629>. Thus, symmetrical disubstituted thioureas are formed by refluxing an ethanol solution of either transfer reagent 3 or 4 with primary amines in a molar ratio of 1:2; moreover, the use of diamines, e.g., 1,2-diaminobenzene and ethylenediamine, provides the corresponding cyclic thioureas. Unsymmetrical di- and trisubstituted thioureas are accessible in very high yields by the sequential treatment of either dithiocarbonyl derivative 3 or 4 with 1 equiv. of a primary amine and 1 equiv. of a primary or secondary amine, respectively, in refluxing ethanol.

S N

N

S + H3C N

SCH3 3

N

–

SCH3 I

4

S 3 or 4

RNH2 (2 equiv.) EtOH/∆

NHR

RHN

R2 = H, Me, aryl, c-C6H11

i. R1NH2 (1 equiv.) 3 or 4

R3 = H, Me

S

EtOH/∆ ii. R2R3NH (1 equiv.) EtOH/∆

R = aryl, alkyl R1 = Ph, benzyl, H

40–96%

R1HN

NR2R3

61–96%

Scheme 23

R2, R3 = –(CH2)5–, –(CH2)2–O–(CH2)2–

556

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

Alternatively, 1,1-thiocarbonyl diimidazole (TCDI) can be regarded as a very common thiocarbonyl transfer reagent to synthesize either symmetrical or unsymmetrical thioureas. Thus, various substituted N-pyridylthioureas with anti-HIV activity have been made accordingly, as illustrated in Scheme 24 <1999BMC2721>. The thioureas resulting from primary amines, TCDI, and 1,2-diaminoarenes are immediate precursors of valuable 2-(alkylamino)benzimidazoles <1999TL1103>. i. TCDI acetonitrile

X N

X

ii. RCH2CH2NH2

NH2

S N

DMF, 100 °C

N H

R

N H

X = Cl, Br, CF3 R = aryl, 1-cyclohexenyl

Scheme 24

Several papers dealing with the solid-phase synthesis of thioureas by thiocarbonyl transfer from TCDI have also been published. For instance, Sun and co-workers <2001TL4119> have described the preparation of 3,4-dihydro-1H-quinazolin-2-thiones (72–97% yield; 60–89% purity) from resin-bound 2-methylaminoanilines, which in turn can be made from Rink resin in three steps (Scheme 25). In a similar way, the solid-phase syntheses of 1,3-disubstituted 2-thioxoquinazoline-4-ones from resin-bound 2-aminobenzamides- <2001TL1749> and of bis-2-imidazolidinethiones from resin-bound tripeptides have been undertaken <2000OL3349>. O N Fmoc H

N

i. TCDI, DMF, rt

N H

H2N NHR

ii. TFA, CH2Cl2, rt 72–97%

O

N H

R S

NH2 R = ArCH2, alkyl

Scheme 25

Recently, the synthesis of a novel C2-symmetric thiourea, as well as its application as ligand in palladium-catalyzed coupling reactions, has been developed. In this case, (1(R), 2(S))-N,N0 (2-methylphenyl)-1,2-diaminocyclohexane was transformed into the corresponding imidazolidine-2-thione in 95% yield by condensation with thiophosgene <2004OL221>. Pentafluorophenyl chlorothioformate has been used as thiocarbonyl transfer agent in the solution and solid-phase synthesis of N-bromobenzyl-N0 -sulfonylthioureas (Scheme 26) <2003JOC1611>. The use of the sulfonamide PbfNH2, as the key reagent to incorporate a TFA-labile guanidine protection group, greatly facilitates the solid-phase synthesis of N,N0 -substituted guanidine compounds.

6.18.1.1.5

From ureas

No relevant new work has been reported in this area since COFGT (1995) <1995COFGT(6)569>.

6.18.1.1.6

Miscellaneous methods

The transfer of both sulfur and nitrogen is also possible according to the report of Valle´e and Byrne which is summarized in Scheme 27 <1999TL489>. They have found that the treatment of isonitriles with the dithioxo-bishydroxylamino molybdenum complex results in the formation of trisubstituted thioureas in good yields. The proposed reaction pathway is also described in Scheme 27.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

Ar

i. ClCS-OC6F5, DIPEA CH2Cl2

NH2

S Ar

N H

ii. PbfNH2, KOtBu DMSO 70%

NHPbf

O Rink amide MBHA resin

557

S

N H

NHPbf

N H

SO2 Ar = Br

Pbf =

CH2

O

Scheme 26

S R N C + Et2N

Mo O

S

S NEt2

CHCl3

RHN

60 °C

O

NEt2

76–82% (R = Bn, c-C6H11) H2O

RN S Et2N +

–

O

RN

S

Mo

S

S

NEt2

Mo Et2N

O

O

NEt2 O

Scheme 27

6.18.1.1.7

From thiocyanate salts and alkyl thiocyanates

The thiocyanate salts represent an attractive alternative to isothiocyanates, particularly when they are difficult to prepare, as it was demonstrated in the past. Recently, the general procedure has been improved and the scope enhanced by Meckler and co-workers <2000S1569>. In this case, high yields of primary monosubstituted or symmetrical N,N0 -disubstituted thioureas can be reached by refluxing potassium thiocyanate and amine hydrochloride in THF or xylenes, respectively (Scheme 28). This approach tolerates sterically bulky primary amines and the resulting thioureas are usually isolated by a simple filtration of the reaction mixture.

S R

N H

THF NH2

reflux 73–96%

R NH2.HCl +

S

Xylenes R reflux

KSCN

N H

N H

R

66–96%

R = alkyl, aryl, (R)-PhCH(Me)

Scheme 28

558

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

Glycopyranosylidene spirothiohydantoins have been prepared from per-O-acetylated 1-bromo1-deoxy--D-glycopyranosacarboxamide, which is in turn available by radical-mediated bromination of the corresponding glycopyranosyl cyanide (Scheme 29) <2001JMC2843>. Heating of a nitromethane solution of the bromoamide and potassium thiocyanate in the presence of a small amount of elemental sulfur resulted in the formation of the spirothiohydantoins in good yields. According to the authors, the reaction probably initiates by a single-electron transfer (SET) from thiocyanate to the bromoamide and involves the coupling of the radicals in the solvent cage.

KSCN S8

R

O

AcO AcO

AcO

R

MeNO2 CONH2

AcO AcO

H N

AcO

80 °C

Br

O

S

O

(R = CH2OAc, H)

N H

64–79 °C

SET

Solvent cage O

SCN CONH2

Scheme 29

In a completely different approach, diastereomerically and enantiomerically pure 4-vinyltetrahydro-1H-imidazole-2-thiones are synthesized from chiral aminoallyl thiocyanates (Scheme 30) <2002T1611>. Thus, these allyl thiocyanates, which are readily accessible from chiral aminoallylic alcohols, lead to the observed cyclic thioureas by a thermal domino reaction consisting of a [3,3]-sigmatropic rearrangement followed by stereocontrolled intramolecular amine addition to the isothiocyanate functionality.

NHBOC OMs

R

Xylene

KSCN MeCN

NHBOC R

85–90%

S

R = Me, Et, Pri, Bn, Bni N Xylene 2-hydroxypyridine (0.1 mol.%) 80 °C, 3 h 80–89%

NHBOC

80 °C 3h

R N C S

S BOC N

NH

R ≥96% de

Scheme 30

The one-pot synthesis of a series of N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thiones was carried out starting from cheap materials such as hydrazines, -bromoketones, and potassium thiocyanate and their anti-HIV and anti-SIV activity studied (Scheme 31) <2003JMC1546>. The mechanism proposed by the authors is outlined in the scheme and involves the [3+2]cycloaddition of 1,2-diazadienes and isothiocyanic acid leading to an azomethine imine dipole as the key step. Finally, the [1,4]-H shift would complete the mechanistic pathway. Alternatively, 1,2,4-triazepine-3-thiones are formed by refluxing in DMF, a mixture of ,-unsaturated ketones and hydrazinediium dithiocyanate <2002TL7481>.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

2

+

R3

R2

S R1 HN N NH

KSCN AcOH

O R1NHNH

30 °C 32–92%

Br

559

R2

R3

–SCN

R1 HN

R1 N

N SCN

R2

R1

S

C

N

NH

R2

R3

–

S +

N N

NH H R3

R2

R3

Scheme 31

In a previous work, Schantl and Na´denı´ k reported that using disubstituted bromoketones, instead of monosubstituted ones, the azomethine imine intermediate cannot stabilize by hydrogen migration, so that a second dipolar cycloaddition to isothiocyanic acid occurs yielding efficiently hexahydro-1H-imidazo[1,5-b][1,2,4]triazole-2,5-dithiones. Overall, the initially formed 1,2-diazadiene undergoes two consecutive [3+2]-cycloaddition reactions to isothiocyanic acid in a ‘‘crisscross’’ fashion (Scheme 32) <1998SL786>.

O

R2

R1 Br

R3

PhNHNH2 KSCN AcOH

S Ph – + N N NH R2 1 R3 R

HNCS

S

Ph N N

S

NH N R3 1 H R R2

R1 = H, R2 = R3 = Me (70%) R1 = H, R2 = Me; R3 = Ph (80%, de = 48%) R1 = Me, R2 = R3 = Me (91%)

Scheme 32

Moreover, Takahashi and Miyadai reported the ‘‘criss-cross’’ cycloaddition of 1,4-diazadienes to trimethylsilylisothiocyanates, as masked isothiocyanic acid, affording moderate yields of perhydroimidazo[4,5-d ]imidazole-2,5-dithiones (Scheme 33) <1990H883>. Later, Pota´cek and co-workers <2002TL4833> undertook a detailed study of the ‘‘criss-cross’’ cycloaddition of 1,4-diazadienes with mixtures of isothiocyanic acid and isocyanic acid, generated in situ from potassium salts and acetic acid (Scheme 33). Although, mixtures of 2,5-dithione and 5-thioxo-2-one derivatives were formed, they found the isothiocyanic acid to be more reactive, the mixed derivatives being best obtained by slow addition of a 2:1 mixture of cyanate/thiocyanate salts to the aldazine in acetic acid.

6.18.1.1.8

From thiocarbamoyl transfer reagents

Nitrosothioureas serve as a useful source of the thiocarbamoyl unit. Thus, the room temperature treatment of aliphatic primary and secondary amines with N-nitroso-1,3-dimethylthiourea (DMNT) leads to very high yields of N-methylthioureas. Starting with N-nitroso-1,3,3-trimethylthiourea (TMNT), the analogous N,N-dimethylthioureas are produced again in high yields (Scheme 34) <1999TL1957>.

560

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

R

N

N

Me3SiNCS THF R

R N

H N

N H

N R

S

rt 24–53%

S

R = c-C6H11, 4-MeOC6H4

R

N

N

R + KOCN

+ KSCN

AcOH

R N

H N

N H

N R

S

rt

X

1:2:1 R

X = O/X = S 84/13 96/4 76/24

c-C6H11 4-MeOC6H4 But

Scheme 33

S Me O

N N

N R1

S

R2R3NH

Me

Me

acetonitrile rt

DMNT (R1 = H)

N R1

NR2R3

93–97% (R1 = H) 65–96% (R1 = Me)

1 = Me)

TMNT (R

R2 = Me, Et, Prn, Pri, Bun, c-C6H11 R3 = H, Me, Et, Prn, Pri, Bun

Scheme 34

As depicted in Scheme 35, methyl N-aryldithiocarbamates were reported to undergo thiocarbamoyl transfer to aminopyridine derivatives <2001JHC457>. Thus, when 2-amino-3-carbethoxy4,6-dimethylpyridine was reacted with various methyl N-aryldithiocarbamates in DMF, the expected thiourea derivatives formed and spontaneously cyclized to 3-substituted 2-thioxo-5,7-dimethylpyrido[2,3-d]pyrimidine-4(3H)-ones in 55–69% yields.

CO2Et Me

N

Me

Me

Me

NH2

S +

Ar

N H

DMF SMe

O

CO2Et Me

N

N H

S NHAr

N 55–69%

Me

N

N H

Ar S

Ar = C6H5, 3-Cl-4-F-C6H3, X-C6H4 (X = 4-Me, 4-F, 4-Cl, 3-Cl)

Scheme 35

Thioglycolic acid (a thiocarbamoyl transfer agent which is readily available from carbon disulfide, a primary or secondary amine and sodium chloroacetate salt) affords aminothiocarbonyl hydrazines upon refluxing with hydrazine hydrate in a basic medium. Their thiosemicarbazones were synthesized by refluxing in water with an alcoholic solution of 5-nitrothiophene-2-carboxaldehyde (Scheme 36) <2002BMC3475>. The overall process takes place with moderate yields and some of the resulting products show significant antimoebic or antitrichomonal activity.

561

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms S

S R1R2N

N2H4.H2O S

CO2H

R1R2N

O2N

CHO

S

NHNH2

NaOH ∆

S R1R2N

∆, 53–74%

N N H

NO2

S

R1 = alkyl, cycloalkyl R2 = alkyl, H R1, R2 = –(CH2)6–

Scheme 36

6.18.1.1.9

From sulfur-transfer reagents

The direct introduction of sulfur from S8 into diaminocarbenes—the so-called Arduengo carbene ligands—can be regarded as a useful entry into cyclic thioureas. Thus, Bildstein and co-workers have reported the preparation of imidazolinethiones, imidazolethiones, and benzimidazolethiones by treatment of the corresponding azolium salts with base and elemental sulfur (Scheme 37) <1999OM4325, 1999JOM(572)177>.

NHFc

FcHN

X

–

Fc N

+

Fc N

MeLi

S

or N Fc

FcN NFc Fc + N

–

S8, 44–56%

Fc N

KOt Bu X

N CH3

N Fc

S N CH3

S8, 98%

(Fc = ferrocenyl)

Scheme 37

The synthesis of 4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazole-2-thiones, whose alkylthioimidazoles are inhibitors of p38 MAP kinase, can be carried out in moderate to good yields by transfer of sulfur from sodium (4-chlorophenyl)methanethiolate to 2-chloroimidazoles as outlined in Scheme 38 <2002AG(E)2290>.

Het

R1 N

Ar1

N

Ar2CH2SNa (4.5 equiv.)

Het

R1 N

Ar1

N

Cl

Ar2 –

SCH2Ar2

Het = pyridin-4-yl Ar1 = 4-F-C6H4 Ar2 = 4-Cl-C6H4 R1 = Ph, Prn, c-C6H11, pyridin-3-yl

Scheme 38

R1 N

Ar1

N H

S

S DMF/∆

Het 51–80%

562

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

The employment of ammonium sulfide for a convenient cyclization of -cyano--(dichloromethyleneimino)alkanoic acids, available from the corresponding isocyanides and chlorine, into 5,5-disubstituted 2,4-dithiohydantoins has been described a few years ago (Scheme 39) <1998S1437>. The reaction is proposed to occur by addition of sulfide and cyclization to a thiazole ring followed by ring opening and new closure.

Cl

S

(NH4)2S (2)

N R1 Cl CO2R2 NC

N H R1 CO2R2

S

acetone, rt

S

HN

H N

58–75%

S

N H R1 CO2R2

R1 = Me, Et, Bu R2 = But

Scheme 39

In 1998 thioketones were first developed as efficient sulfur transfer agents towards azole N-oxides providing a new synthetic method for the thiourea function (Scheme 40) <1998HCA1585>. Thus, substituted imidazole 3-oxides react with some thioketones (2,2,4,4tetramethyl-cyclobuta-1,3-dithione, 2,2,4,4-tetramethyl–1-thioxo-cyclobutan-2-one, and adamantine-2-thione) to give imidazole-2(3H)-thiones in high yield. Triazole oxides can also be transformed equally well into triazolethiones. O– N

R3 R2

+

+

CHCl3

R

rt 65–96%

R

CHCl3

R

rt 84%

S

N R1

EtO2C

R3

R

–

+

N

O

+

R1 = alkyl R2, R3 = Me, Ph

R2

H N N Ph

S

S

R =

S

S

N R1

EtO2C

S

N Ph

H N

;

S

X

R (X = O, S)

Scheme 40

Taking advantage of this procedure, Laufer and co-workers <2002AG(E)2290> have synthesized a structurally diverse imidazole thiones during their studies directed to develop new inhibitors of p38 MAP kinase with a 4,5-disubstituted alkylthioimidazole framework (Scheme 41). The required imidazole oxides are obtained in high yields by refluxing in ethanol a mixture of 1-(4-fluorophenyl)-2-(pyridin-4-yl)hydroximinoethan-2-one and the corresponding 1,3,5-trisubstituted hexahydro-1,3,5-triazine. In the course of their studies of adenosine-derived monomeric building blocks for new oligonucleosides, Gunji and Vasella <2000HCA1331> showed the ability of N-phenylthiourea as sulfur-transfer agent to 2-halogenoimidazoles (Scheme 42). Thus, the 2-chloro and 2-iodo nucleosides were transformed into the corresponding thioxo nucleosides upon heating with N-phenylthiourea at 60 C. Molina and co-workers <2000TL4895> have reported a rather unexpected sulfur-transfer reaction from carbon disulfide which is the basis of a new synthesis of dihydroquinazoline2-thiones (Scheme 43). The process comprises the intramolecular heteroconjugate addition of

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

563

aromatic carbodiimides bearing an o-substituted ,-unsaturated carbonyl fragment promoted by the carbon disulfide/tetrabutylammonium fluoride. The mechanism proposed by the authors nicely accounts for the complex transformation and involves cyclization induced by attack of the S-nucleophile fluorodithioformate, generated from CS2-TBAF, followed by thioacyl fluoride hydrolysis and fragmentation to the thione group and C(S)O.

Het

(CH2=NR)3

O

Ar

EtOH/∆ 50–89%

NOH

Het

R N

Ar

N – O

S

Het

R N

Ar

N H

S

S

+

CHCl3, rt 60–98%

Het = pyridyn-4-yl Ar = 4-fluorophenyl R = Me, Prn, c-C3H7, R2N(CH2)2, 3, RO(CH2)3

Scheme 41

S OR1 N

N

O

R2

N X O

O

NHBz

N

NHBz

N

PhHN

OR1 N NH2

NH

O

R2

N S

toluene, 60 °C 82–98%

O

O

R1 = Et3Si R2 = Me3Si C C X = Cl, I

Scheme 42

O O R2

N

CS2/ TBAF (4:1)

N C N R1

S

N H

25 °C

R2 R1

40–50% S F

O

+

Bu4N

N R

1 = Ar,

Bn

+

–

–

S

N

–S C O

Bu4N

–TBAF

R2 R1

H2O S

S F

R2 = Fc, OMe

Scheme 43

Finally, N,N-unsubstituted thioureas are accessible in moderate-to-high yield by sulfur transfer from LiAlHSH, generated in situ by mixing LAH and sulfur, to chloroamidines, as depicted in Scheme 44 <2001TL6333>.

564

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms LiAlHSH

NH HCl R

N R

NH R

Cl

THF, 0 °C

N R

S

SH

R 51–89%

N R

NH2

R = Me, Et R-R = –(CH2)4,5–

Scheme 44

6.18.1.2 6.18.1.2.1

Thiocarbonyl Derivatives with One Nitrogen and One Phosphorus Function From isothiocyanates

The addition of the PH bond of phosphines to isothiocyanates, as well as the lone pair of substituted phosphines, continues to be the most valuable method for preparing phosphinothioformamides. For instance, bis(2-phenethyl)phosphine adds to 2-(vinyloxy)ethyl isothiocyanate under thermal reaction conditions to produce the expected N-(2-vinyloxyethyl thiocarbamoyl)phosphine in excellent yield. Similarly, the addition of the phosphine oxide analog to the isothiocyanate and stirring in refluxing benzene results in the formation of the corresponding N-(2-vinyloxyethylthiocarbamoyl)phosphine oxide (Scheme 45) <1999JOU212>. O S R2P

R2PH NHR1

R2P R1 N C S

70 °C, 90%

H

C6H6, reflux, 95% R2P O

S NHR1

R = PhCH2CH2 R1 = CH2=CH-O-CH2CH2

Scheme 45

Phosphines bound to transition metals have frequently been reacted with isothiocyanates in order to effect structural modification on the coordination sphere in phosphine-containing metal complexes. Malisch and co-workers <1998ZN(B)1084> have prepared various P-mesitylferrio(thiocarbamoyl)phosphines by reaction of P-mesitylferriophosphine with alkyl and phenyl isothiocyanates (Scheme 46). The thiocarbamoylphosphines thus obtained were in turn P-alkylated with alkyl halides or oxidized with elemental sulfur. In addition, the authors communicated that the ferrio-(t-butyl)phosphine analog reacts with 2 equiv. of methyl and ethyl isothiocyanate to produce P-thiocarbamoylphosphametallacycles (Scheme 46). The formation of these adducts can be rationalized by formal [3+2]-cyclization of isothiocyanate and the metal complex, via the phosphine and CO ligands, followed by insertion of the second molecule of heterocumulene into the PH bond <1998JOM(568)247>. Molybdenum and tungsten phosphenium complexes Cp(CO)2M¼PH-t-Bu undergo a [2+2]cycloaddition reaction to alkyl isothiocyanates furnishing the four-membered phosphametallacycles. Furthermore, insertion of the isothiocyanate into the PH bond of these systems occurs and the corresponding thiocarbamoyl phosphine derivatives are obtained in high yields (Scheme 47) <2000JOM(595)285>. In a closely related process, deprotonation of the dinuclear phosphine complex shown in Scheme 47, followed by addition of phenyl isothiocyanate and nitrogen protonation gives the expected complex in 85% yield <2000OM984>. The ferrio-diphenylphosphine Cp(CO)(PMe3)Fe-PPh2, formed from Cp(CO)2Fe-PPh2 by CO/ PMe3 ligand exchange, readily adds to methyl isothiocyanate giving rise, after protonation with triflic acid, to the cationic open-chain thiocarbamoylphosphine iron complex (Scheme 48) <1998ZN(B)1077>. Structurally related complexes of iron and ruthenium, formed in situ by deprotonation of their cationic precursors with KO-t-Bu, add to methyl isothiocyanate to

565

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

generate an open-chain adduct, which suffers further cyclization by means of nucleophilic addition to a carbonyl ligand (Scheme 48) <1998JOM(568)241>. The corresponding acyclic addition product would be available by acid treatment.

R S

R1NCS

Mes Cp(CO)2Fe P H

S R2 P NHR1 X Mes

Cp(CO)2Fe

2X

Cp(CO)2Fe

P NHR1 Mes

R1 = Me, Et, Ph Mes = mesityl

t Cp Bu

2RNCS Cp(CO)2Fe-PH-But R = Me, Et

O

N R

NHR1

S

OC Fe P

toluene 25 °C, 69–76%

S

Mes Cp(CO)2Fe P S

S

NHR S

Scheme 46

RNCS Et3N

H [M]

H t P Bu

[M]

P

toluene 25 °C

But

S RNCS 74–93%

S

NHR P But

[M] S

N R

N R

[M] = Cp(CO)2Mo, Cp(CO)2W

R = Me, Et, But P

P Cp(CO)2Mo

Mo(CO)Cp PHPh2

i. DBU ii. PhNCS, 25 °C

P Cp(CO)2Mo

iii. HBF4, 85%

P Mo(CO)Cp

Ph2P

NHPh S

Scheme 47

S i. MeNCS

Cp(Me3P)(CO)FeP NHMe Ph Ph

Cp(CO)(PMe3)FePPh2 ii. TFA

+

Cp(CO)2M-PHR1R2 M = Fe, Ru R1 = But, Pri, Ph

X

–

KOBut Me-NCS

toluene 25 °C, 68–83%

Cp

R1

S

OC M P R2 O

+

N Me

R2 = But, Pri, Ph

Scheme 48

S

HX M = Fe R1 = Ph R2 = Ph 98%

+

Cp(CO)2FeP NHMe X Ph Ph

–

566

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

Majoral and co-workers <1999OM1882, 2000CEJ345> have carried out an extensive study on the reactivity of bi- and tricyclic -zirconated phosphanes and various cumulenes, e.g., isothiocyanates (Scheme 49). Thus, -phosphinozirconacycles and methyl and phenyl isothiocyanates afford stable zwitterionic tri- and tetracyclic five-membered anionic zirconium complexes in moderate-to-high yields.

RNCS

+

–

PPh2

Zr

Cp

Cp

toluene 25 °C, 53–73%

Cp Zr Cp N R

PPh2 S

R = Me, Ph

PhNCS P

Zr Cp

Cp

Ph

toluene – 40 °C, 91%

P Ph Cp Zr Cp N S Ph

Scheme 49

Interestingly, the PSi bond is capable of inserting into the C¼N bond of isothiocyanates in the same way as does the PH bond. This makes it feasible to prepare unconventional systems such as thiocarbamoyl phosphaalkenes, as reported by Weber and co-workers (Scheme 50) <1998OM3593>. The reaction of the phosphaalkene (Me2N)2C¼P-SiMe3 with phenyl isothiocyanate in pentane at low temperature furnishes the expected adduct in 72% yield.

Me2N P SiMe3

P pentane –30 °C, 72%

Me2N

S

Me2N

PhNCS

Me2N

N Ph

SiMe3

Scheme 50

Cyclic systems, such as thioxoazaphospholes, have recently been described by Ruiz and co-workers (Scheme 51) <2002CEJ3872>. They started with the diphosphanyl ketenimine, which was first transformed into the monooxidized derivative by crystallization-induced cyclodimerization, followed by H2O2 oxidation and thermal dedimerization. The oxidized diphosphanyl ketenimine behaves as a 1,3-dipole towards ethyl isothiocyanate affording the [3+2]-cycloadduct in 70% yield.

i. Crystall. Ph2P C C N Ph Ph2P

O

O

ii. H2O2

Ph2P

iii. Toluene reflux 81%

Ph2P

C C N Ph

EtNCS toluene reflux 70%

N Ph

Ph2P N Et Ph P Ph S

Scheme 51

6.18.1.2.2

From halothioamides

A facile synthesis of diphenylphosphino-N,N-dimethylthioamide, a simple and useful ligand in organometallic chemistry, has been achieved in moderate yield and comprises the treatment of sodium diphenylphosphide with dimethylthiocarbamoyl chloride (Scheme 52) <2001JCS(D)309>.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms i. Na / THF Ph2PH

567

S NMe2

Ph2P

S ii. NMe2

Cl

THF, 25 °C 55%

Scheme 52

6.18.1.2.3

From thiophosphinoyldithioformates

No relevant new work <1995COFGT(6)569>.

6.18.1.2.4

has

been

reported

in

this

area

since

COFGT

(1995)

From phosphonodithioformates

A large number of phosphonate derivatives have been reported by amination of methyl phosphonodithioformates with primary and secondary amines as well as with ammonia (Scheme 53) <1994ZOB1639, 1994PS119>. S (RO)2P

S

R1R2NH (RO)2P

SH

O

NR1R2

O R1 = R2 = H; R1 = H, R2 ≠ H; R1, R2 ≠ H

Scheme 53

6.18.1.2.5

Miscellaneous methods

Renard and Mioskowski have utilized various phosphorus reagents to create phosphorus–sulfur bonds. Accordingly, the synthesis of a number of phosphonothioates is readily achieved by the reaction of the phosphorus precursors with alkylthiocyanates in the presence of the hindered, nonnucleophilic base phosphazene P4-t-Bu (Scheme 54, via A) <2002CEJ2910>. Unexpectedly, the heating of ethoxyphenyl phosphinate with cyclohexylthiocyanate in the presence of diisopropylethylamine, instead of phosphazene, results in the exclusive formation of the (cyclohexylamine)thioxomethyl phosphinate derivative (via B). Obviously, the formation of the thiocarbamoylphosphine derivative requires that the phosphorus–carbon bond formation be preceded by the thermal isomerization of cyclohexylthiocyanate to cyclohexylisothiocyanate.

c-C6H11 S C N

via A

+

O Ph P H OEt

via B Pr2NEt EtO DMF 110 °C 78%

Phosphazene P4-t-Bu 82%

O Ph P S c-C6H11 OEt

Scheme 54

Ph P O

S NH-c-C6H11

568

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

According to Morita and co-workers <1999TL2327>, different phosphine carbothioamides are available in moderate yields by heating tetrazolylsulfinylmethyl(dimethyl)phosphine oxide in the presence of primary and secondary amines (Scheme 55). The resulting compounds are thought to be formed by the addition of amines to the sulfine formed initially, followed by elimination of water.

Ph N

N N N

-

Ph N

N N N

O S

S

R1R2NH

O PMe2

R1R2N dioxane 70 °C 50–53%

R1R2NH –H2O

O

H S H

PMe2 O

PMe2 O

Scheme 55

6.18.2

FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION

This class of compounds is very rare in the literature. In fact a few examples of silicon-containing derivatives were collected in the COFGT (1995) report. In the present update review, isolated systems containing two phosphorus functions and two silicon functions are given.

6.18.2.1

Thiocarbonyl Derivatives with Two Silicon Functions

Bis(trimethylsilyl)thioketone S-oxide represents certainly an island in the context of this sort of silicon functionality. In this particular case, tris(trimethylsilyl)methyllithium was reacted with SO2 in THF to provide that functional system in 41% yield (Scheme 56) <2000CJC1642>.

O S (Me3Si)3C-Li +

SO2 THF 41%

Me3Si

SiMe3

Scheme 56

6.18.2.2

Thiocarbonyl Derivatives with Two Phosphorus Functions

Taking advantage of the reversible SS bond breaking and bond formation in dinuclear complexes of Mn(I) containing the disulfide function, Ruiz and co-workers <2001AG(E)220> have reported a method for accessing a mononuclear (diphosphanylthioketone)manganese complex (Scheme 57). Thus, the starting disulfide-containing dinuclear complex 5 transformed instantaneously into the sulfenyl iodide mononuclear complex 6 upon treatment with 1 equiv. of iodine. Further iodide abstraction by using either excess of iodine or TlPF6 produces the desired diphosphanylthioketone complex 7. The direct conversion of the disulfide 5 into 7 was accomplished by oxidation of the sulfur–sulfur bond with 2 equiv. of AgBF4.

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Ph

Ph

I2

P (CO)4Mn

Ph

Ph

Ph

Ph P 2 (CO)4Mn

S P

CH2Cl2 2

569

S

I

P Ph

Ph 6

5 AgBF4 CH2Cl2

I2 or TIPF6

–Ag +

40%

Ph

Ph P 2 (CO)4Mn

S P

Ph

Ph

7

Scheme 57

REFERENCES 1990H883 1992JA7001 1994PS119 1994S719 1994ZOB1639 1995COFGT(6)569

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Ila, H. Junjappa, Tetrahedron 2000, 56, 629–637. 2000T6899 G. Kaupp, J. Schmeyers, J. Boy, Tetrahedron 2000, 56, 6899–6911. 2000TA435 C. Gasch, M. A. Pradera, B. A. B. Salameh, J. L. Molina, J. Fuentes, Tetrahedron Asymmetry 2000, 11, 435–452. 2000TL4895 A. Tarraga, P. Molina, J. L. Lo´pez, Tetrahedron Lett. 2000, 41, 4895–4899. 2000TL5069 H. S. Oh, H.-G. Hahn, S. H. Cheon, D.-C. Ha, Tetrahedron Lett. 2000, 41, 5069–5072. 2000TL8333 S. Makino, N. Suzuki, E. Nakanishi, T. Tsuji, Tetrahedron Lett. 2000, 41, 8333–8337. 2001AG(E)220 J. Ruiz, M. Ceroni, O. V. Quinzani, V. Riera, O. E. Piro, Angew. Chem. Int. Ed. 2001, 40, 220–222. 2001JCS(D)309 P.-H. Leung, Y. Qin, G. He, K. F. Mok, J. J. Vittal, J. Chem. Soc. Dalton Trans. 2001, 309–314. 2001JHC457 C. G. Dave, K. J. Patel, J. Heterocycl. Chem. 2001, 38, 457–461. 2001JMC2843 L. Somsa´k, L. Kova´cs, M. To´th, E. Osz, L. Szila´gyi, Z. Gyo¨rgydea´k, Z. Dinya, T. Docsa, B. To´th, P. Gergely, J. Med. Chem. 2001, 44, 2843–2848. 2001MI129 R. 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Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

571

Biographical sketch

Jose´ Barluenga studied chemistry at the University of Zaragoza and received his doctorate in 1966. He spent three and a half years as a postdoctoral research fellow of the Max Planck Gesellschaft at the Max Planck Institut fu¨r Kohlenforschung (Mu¨lheim a.d. Ruhr, Germany) in the group of Professor H. Hoberg. In 1970 he became Research Associate at the University of Zaragoza where he was promoted to Associate Professor in 1972. In 1975 he moved to the University of Oviedo as Professor in Organic Chemistry, where he is currently Director of the Instituto Universitario de Quı´ mica Organometa´lica ‘‘Enrique Moles.’’ His major research interest is focused on developing new synthetic methodologies in organic chemistry by means of organometallic reagents as well as iodine-based systems.

Eduardo Rubio (Logron˜o, Spain, 1959) received his B.A. degree in Oviedo and got his Ph.D. under the supervision of Professors Barluenga and Toma´s in 1989. He carried out postdoctoral studies at MIT (Alex Klibanov, enzymes in organic solvents, 1989–1990) and at the University of California, Berkeley (Peter Vollhardt, organic synthesis mediated by organometallic reagents, 1990–1991). He returned to the University of Oviedo and got a position as Profesor Titular in 1996. From 2000 he is the secretary of the Instituto Universitario de Quı´ mica Organometa´lica ‘‘Enrique Moles,’’ where he continues his research. His main research interests are synthetic and mechanistic chemistry and the application of NMR to the study of reaction mechanisms.

572

Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms

Miguel Toma´s received his B.A. degree in chemistry from the University of Zaragoza in 1974 and his Ph.D. degree from the University of Oviedo in 1979. He was a postdoctoral fellow (1981–1983) in the research group of Professor A. Padwa at Emory University (Atlanta, USA) working on 1,3-dipolar cycloadditions. Then, he returned to the University of Oviedo where he was appointed Profesor Titular in 1985 and promoted to Professor of Organic Chemistry in 1996. His major research encompasses the use of transition metal reagents, particularly metal carbene complexes, as flexible intermediates in organic synthesis and the design of new metal-catalyzed processes.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 545–572

6.19 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group—SeC(X1)X2 and TeC(X1)X2 L. J. GUZIEC and F. S. GUZIEC, Jr. Southwestern University, Georgetown, TX, USA 6.19.1 OVERVIEW 6.19.2 SELENO- AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHED HALOGEN 6.19.2.1 Seleno- and Tellurocarbonyl Compounds Containing Two Attached Halogen Atoms 6.19.2.2 Seleno- and Tellurocarbonyl Compounds Containing One Attached Halogen Atom 6.19.3 SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHED CHALCOGEN (AND NO HALOGENS) 6.19.3.1 Dialkoxy-substituted Selenocarbonates (RO)2C¼Se 6.19.3.2 Dithio-substituted Selenocarbonates (RS)2C¼Se 6.19.3.3 Diseleno-substituted Selenocarbonates (RSe)2C¼Se 6.19.3.4 Selenocarbonyl Functions Flanked by Two Different Chalcogen Atoms RX(C¼Se)Y 6.19.3.5 Selenocarbamates RO(C¼Se)NHR, RS(C¼Se)NHR, RSe(C¼Se)NHR, RTe(C¼Se)NHR 6.19.4 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 6.19.4.1 Selenoureas (R2N)2C¼Se 6.19.4.2 Other Cyclic N(C¼Se)N Compounds 6.19.4.3 Telluroureas (R2N)2C¼Te 6.19.5 HYPERVALENT SELENOCARBONYL COMPOUNDS OF THE TYPE Se¼C(X)X0

6.19.1

573 574 574 574 576 576 576 578 580 581 584 584 588 590 591

OVERVIEW

As previously reported in chapter 6.19, COFGT (1995) <1995COFGT(6)587>, seleno- and tellurocarbonyl derivatives of common carbonyl-based functional groups are much less well known than their corresponding oxygen or sulfur analogs. The comparative rarity of the seleno- and tellurocarbonyl compounds has been primarily due to their decreased stability as a result of poor -overlap in C¼Se and C¼Te bonds. In the period 1993–2003 ingenious use of new reactions and novel reagents have made previously rare structures much more readily available for investigation. Particularly noteworthy in this period are reports of hypervalent halogen adducts of selenocarbonyl compounds, a topic not originally covered in COFGT (1995) <1995COFGT(6)587>. 573

574 6.19.2

6.19.2.1

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group SELENO- AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHED HALOGEN Seleno- and Tellurocarbonyl Compounds Containing Two Attached Halogen Atoms

Compounds containing a halogen atom directly attached to a seleno- or tellurocarbonyl function remain quite rare <1995COFGT(6)587>. Both selenocarbonyl difluoride 1 and tellurocarbonyl difluoride 2 have been prepared by careful reaction of mercury salts with Lewis acid. Both of these compounds are unstable and rapidly dimerize. The reactivity of the tellurocarbonyl compound greatly exceeds that of the corresponding selenocarbonyl species. An improved method for the preparation of monomeric tellurocarbonyl difluoride involves pyrolysis of the stannyl telluride (Equation (1)) <1993JCS(D)2547>. Dimerization to the corresponding ditelluretane rapidly occurs at temperatures above 77 K. Co-condensation of 1 and 2 affords the mixed selenium– tellurium dimer. In situ generated tellurocarbonyl difluoride can also be trapped as its cycloaddition product with 2,3-dimethylbutadiene (Scheme 1).

F

F

Se

Cl

Te

Se

F

F

1

Cl 3

2

i

F

Me3SnTeCF3

Te

> –196 °C

F

50–60%

F

Te F

F

Te F

ð1Þ

i. FVP, 280 °C

F Se F F Te

F

Te F

F

Se F

F Te F F

Scheme 1

Selenophosgene 3 has been suggested as an intermediate in Willgerodt–Kindler-type reactions of trichloroacetic acid or chloroform with base and elemental selenium in the presence of amines to form selenoureas <1996BCJ2235> (see Equation (30)).

6.19.2.2

Seleno- and Tellurocarbonyl Compounds Containing One Attached Halogen Atom

N,N-Dimethylselenocarbamoyl chloride 4 can be prepared quantitatively by treatment of dichloromethylene dimethyliminium chloride with lithium aluminum dihydroselenide (Equation (2)) <2002JOC1008>. This selenocarbamoyl chloride is an extremely useful reagent for the preparation of diselenocarbamates, thioselenocarbamates, and selenoureas (see Sections 6.19.3.5 and 6.19.4.1). The conversion of other dialkyliminium salts into the corresponding selenocarbamoyl chlorides should significantly simplify the preparation of a variety of other interesting selenocarbonyl compounds.

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

Me2N CCl2

Cl

LiAlHSeH, 0 °C

Se Me2N C Cl

Quantitative

4

575

ð2Þ

A number of unstable selenocarbonyl fluorides can be prepared by treatment of perfluorinated mercuric selenides with diethylaluminum iodide or aluminum iodide (Equation (3)) <1991CB51>. These compounds rapidly polymerize, but the polymers upon heating can be converted to the monomeric or dimeric materials. The monomeric selenocarbonyl compounds can be trapped by cycloaddition with cyclopentadiene (Scheme 2). Se

Et2AlI

(RSe)2Hg

Se F

R

R = CF3CF2CF2–, CF3CF2–, CF3–

R

F

n

ð3Þ

R = CF3CF2–, CF3–, CF3Se–

∆

Se

F

R

35 – 45%

Se R

n

R

Se R

F

Se F

F R

R = CF3CF2–, CF3–

Se

F

Scheme 2

Flash vacuum pyrolysis (FVP) of perfluorinated trimethyltin tellurides affords isolable tellurocarbonyl fluorides which dimerize at low temperature to the corresponding ditelluretanes 5 (Equation (4)) <1996JCS(D)4463, 2000JCS(D)11>. The tellurocarbonyl fluorides can also be trapped as their cycloadducts with dienes (Equation (5)) <1997PS(124)413>. Although no tellurocarbonyl analogs of acyl chlorides have been reported, the ‘‘dimeric’’ dichloroditelluretane 6 can be isolated by reaction of the difluoro compound with boron trichloride (Equation (6)).

Me3SnTeR

Te

FVP F

R1

> –196 °C

R1

Te R1

49–64%

F

Te F 5

R = CF3CF2–, CF3CF2CF2–, CF3(CF2)2CF2–

ð4Þ

R1 = CF3–, CF3CF2–, CF3CF2CF2–

Te Me3SnTeCF2CF2CF3

F CF3CF2

160 °C

Te F Te CF2CF3

Te CF3CF2

F

– 40 °C to 22 °C BCl3 82%

ð5Þ

F CF2CF3

75%

Cl CF3CF2

Te Cl Te CF2CF3 6

ð6Þ

576 6.19.3

6.19.3.1

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHED CHALCOGEN (AND NO HALOGENS) Dialkoxy-substituted Selenocarbonates (RO)2C¼Se

Dialkoxy-substituted selenocarbonyl compounds remain quite rare in the literature <1995COFGT(6)587>. O,O-Diethylselenocarbonate 7 has been prepared from tetraethylorthocarbonate by the use of bis(dimethylaluminum)selenide (Equation (7)) <1992TL7865>. Attempts at using this reagent for the direct conversion of the carbonyl group to the selenocarbonyl group in other related compounds were unsuccessful.

(EtO)4C

(Me2Al)2Se

+

Toluene, dioxane 80 °C

Se EtO

74%

ð7Þ

OEt 7

6.19.3.2

Dithio-substituted Selenocarbonates (RS)2C¼Se

A variety of synthetic routes have been available for the preparation of cyclic dithio-substituted selenocarbonates, important precursors for the synthesis of tetrathiafulvalenes <1995COFGT(6)587>. A number of routes for the preparation of these selenocarbonates start from the corresponding thiocarbonyl compounds. Selective S-alkylation followed by treatment with sodium hydrogen selenide affords the desired selenocarbonyl derivatives in good yield (Equation (8)) <1994JOC5324, 1998JOC8865>. Some additional examples of this transformation in the preparation of various complex dithio-substituted selenocarbonates have also appeared (Equation (9)) <1997JOC1903, 1998JOC8865>. The utilization of the selenocarbonate–diene intermediate 8 appears to be a particularly interesting approach for the introduction of the dithioselenocarbonate moiety into complex molecules (Scheme 3) <2002JMAC2137>. O

O S

Ph

i. CF3SO3CH3 ii. Se, NaBH4, PhCOCl

S S

Ph

S

S

Ph

S

ð8Þ

Se

S

76%

O

Ph

S

S

O

S

i–iii

S Se

S S

S

ð9Þ

i. CF3SO3Me, 91%; ii. Se, H2O, NaBH4; iii. AcOH, toluene, 59% for two steps

The thiocarbonyl group of a cyclic trithiocarbonate group can also be converted to the corresponding selenocarbonyl moiety using triethyl orthoformate in the alkylation step (Scheme 4) <1994CHE652>. Subsequent base promoted cyclization afforded thieno[2,3-d]-1,3-dithiol-2-selone 9. Related heterocyclic dithioselenocarbonates could be readily incorporated into the corresponding complex tetrathiafulvalenes <1992CHE945, 1994CHE1116>. A variety of complex heterocyclic dithioselenocarbonates have also been prepared using the reaction of N,N-dialkyldithiocarbamate salts with sodium hydrogen selenide (Schemes 5 and 6) <1992CHE941, 1993CHE1316, 1993CHE1432>.

577

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group S

HO HO

i–iii S

76%

S

S

HO HO

iv Se

58%

S

S

Br Br

Se S v

S Se S

C60

S

25%

S

Se 8

i. MeI, THF, 91%; ii. Se, H2O, NaBH4; iii. AcOH, toluene; iv. PBr3, THF, CCl4; v. KI, 18-crown-6, toluene

Scheme 3

O S

MeO

O

i. HC(OEt)3, BF3·Et 2O ii. NaHSe

S

S

MeO

S

S

Se

S

MeO

S

MeO

27%

O

O i, ii Quantitative S

MeO

S

O H O

Se

S

i. NaOMe; ii. H+

9

Scheme 4

O

O S

HN H2N

i, ii

+

NEt2 N

HN

76%

S

H2N + N H

ClO4

Se S C NEt2

O iii, iv 50%

S

S

HN H2N

Se N

i. Na2Se; ii. AcOH; iii. HCl, AcOH, heat; iv. DMF, pyridine, H2O

Scheme 5

O Me O

N N Me

S S C NEt2

O Me

i. Conc. H2SO4 ii. NaClO4

O

S

N

O

S

N Me

ClO4

i 66% O Me O

S

N

Se N Me

S

Scheme 6

+

NEt2

i. Na2Se, H

+

S

578

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

The metallation–chalcogenation sequence performed on the mixed sulfur–selenium substituted thione 10 leads to a ‘‘Dimroth rearrangement’’ affording the selenocarbonyl complex, which can be further transformed into other selenocarbonate derivatives (Scheme 7) <1992JOM(427)213>.

S S Se

Se

i–iv 32%

S

(Bu4N)2 Zn

v

Se Se

S

S

PhCOSe

S

Se

61%

2

PhCOSe

10 i. LDA / THF, –78 °C, 2 h; ii. Se, –78 °C 1 h, rt, 2 h; iii. ZnCl2 , MeOH, NH3; iv. Bu4NBr, MeOH; v. PhCOCl, acetone

Scheme 7

6.19.3.3

Diseleno-substituted Selenocarbonates (RSe)2C¼Se

Cyclic triselenocarbonates are important intermediates in the synthesis of tetraselenafulvalene derivatives and numerous methods have been used in the preparation of these compounds <1995COGFT(6)587>. A novel approach to the preparation of the unsymmetrical triselenocarbonate 11 involves metallation of the protected acetylene followed by consecutive treatment of the lithium salt with selenium, carbon diselenide, and methyl iodide (Equation (10)) <1998JOC8865>. A variety of other triselenocarbonate derivatives <1997SL319> including bridged bis(1,3-diselenole-2-selones) 12 have also been prepared using this procedure (Equation (11)) <1998AG(E)619>. OTHP

OTHP

Se

i–iv Se

Se

70%

SeMe

11

ð10Þ

i. BunLi, TMEDA, THF, –70 °C ii. Se, 0 °C iii. CSe2, Se, –70 °C iv. MeI

i. BunLi, THF

Se Se

ii. Se, 0 °C

( CH2)

S C CH

n S C CH

iii. CSe2,

S

Se

n S

Se

( CH2)

51–58%

ð11Þ Se

Se 12

The lithium intermediate in this reaction can also be trapped by the addition of an alkyl isothiocyanate introducing a sulfur substituent on the diselenole-2-selone ring (Equations (12) and (13)) <2001AG(E)1122, 2001JMAC1026, 2002JOC4218>. This lithium intermediate can also be generated by metallation of 1,2-dichlorovinylmethyl sulfide <2003JOC5217>. The potential versatility of these methods has been shown with the use of the acetylenic silane in this transformation (Scheme 8) <2000EJO3013>. i, ii, iii Me S C CH

73%

Se

SMe

Se

S

Se

O OMe

i. BunLi, –78 °C, THF; ii. Se; iii. CSe2; iv. MeO2CCH2CH2SCN

ð12Þ

579

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

HC C

i–iv

S

S

Se

OTHP

OTHP

Se Se

71–73%

SR

ð13Þ

i. BunLi, TMEDA, –70 °C ii. Se, 0 °C iii. CSe2, –90 °C iv. RSCN

i, ii, iii Me3Si

SiMe3

Se

C CH

+

Se Se

i. BunLi, –78 °C, THF; ii. Se, 0 °C

Se

SiMe3

Se

S

O

Se

OMe

(Bun)4NF

iii. CSe2, –90 °C, MeO 2CCH2CH2SCN Se

Se +

Se

O

Se

Se

Se

S

OMe

66%

Scheme 8

Reactions of iminium salts with hydrogen selenide are widely used in the preparation of triselenocarbonates. This route has been used for the preparation of triselenocarbonates containing a 13C labeled selenocarbonyl group (Scheme 9) <2001MI1035>.

Se

i, ii

N * Se

O

Se * Se

+ N

86%

Se * Se

iii 53%

Se

PF6– i. H2SO4; ii. HPF6; iii. H2Se, EtOH * denotes 13C

Scheme 9

Electrochemical reduction of carbon diselenide provides a convenient route to the diseleniumsubstituted diselenol-2-selone (Scheme 10) <2001S1614>.

2 e–

2 CSe2

–

Se

–

Se

Se Se

CSe2

Se

Se

Se

–CSe3–2

Se

2 e–

Se

Se–

Se

Se–

Se

Se

Bun4 NBr, ZnCl2 82% Se Se Se

Se Se

CO2Me CO2Me

Br(CH2)2CO2Me

Se

Se

Se

Se

Zn

Se 82%

Scheme 10

2

(Bun4 N)2

580

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

Cyclooctyne reacts with carbon diselenide in the presence of selenium to afford the corresponding triselenocarbonate 13 (Equation (14)) <2000JOC8940>. +

Se

CH2Cl2, reflux

CSe2 + Se

Se Se

59%

ð14Þ

13

6.19.3.4

Selenocarbonyl Functions Flanked by Two Different Chalcogen Atoms RX(C¼Se)Y

Compounds with the selenocarbonyl group attached to two different chalcogen atoms have until the late 1990s been relatively rare <1995COFGT(6)587>. Increased interest in mixed fulvalene derivatives has led to novel approaches for the preparation of these compounds. The abovementioned metallation route to diselenole-2-selones (Section 6.19.3.3, Equations (10)–(13)) can be readily applied to the preparation of the corresponding sulfur–selenium heterocycles. Treatment of the protected lithiated acetylene with sulfur followed by carbon diselenide and selenium and trapping with ethyl iodide affords the desired selenocarbonate 14 (Equation (15) <2002JOC4218>. This method was also used for the preparation of novel 1,3-selenatellurole2-selones such as 15 (Equation (16)) <1997CC1925, 2001PS(171–172)231>. Extension of this reaction to other substituted acetylenic precursors and trapping with various electrophiles should make this method a very versatile route to the mixed chalcogen-substituted selones. HC C

S

S

Se

i–iv

OTHP

OTHP

Se

73%

S

SeEt

i. BunLi, TMEDA, –70 °C

ð15Þ

14

ii. S, 0 °C iii. CSe2, –90 °C iv. Se, EtI, 0 °C Me3Si

Te

i–iv

C CH

83%

Se Se

ð16Þ

15 i. BunLi; ii. Te; iii. CSe2; iv. H2O

Another interesting metallation route affords the mixed sulfur–selenium heterocyclic selenocarbonate 16 via an iminium salt intermediate (Scheme 11) <1998JMAC1945>. A similar reaction of an iminium salt with hydrogen selenide affording a related selenocarbonate has also been reported <1992ZN(B)898>. O O

O

i

O

O

Li

O

ii, iii 68%

Se

N S

O

iv, v

O

vi

Se

O

Se

Se S

O

+

N 11%

O

O

S Br –

16

i. BuLi (1 equiv.), 0 °C; ii. Se, THF, –35 °C; iii. morpholino-4-thiocarbonyl chloride, –78 °C; iv. Br2, CH2Cl2; v. 110 °C; vi. Se, NaBH 4, AcOH–EtOH

Scheme 11

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group 6.19.3.5

581

Selenocarbamates RO(C¼Se)NHR, RS(C¼Se)NHR, RSe(C¼Se)NHR, RTe(C¼Se)NHR

A variety of methods have been described for the preparation of selenocarbonyl derivatives of urethanes <1995COFGT(6)587>. Since 1995 there has been significantly increased interest in developing new synthetic methods in this area. Treatment of N,N-dimethylselenocarbamoyl chloride (Section 6.19.2.2) with readily prepared lithium thiolates and selenolates provides a convenient route to N,N-dimethylamino-substituted thioseleno- and diselenocarbamates (Scheme 12) <2002JOC1008>. The use of other substituted selenocarbamoyl chlorides should make this a very useful general method for the preparation of other interesting selenocarbamate derivatives. +

Me2N CCl2

Cl–

LiAlHSeH, 0 °C

Se Me2N C Cl

RSeLi

RSLi

Se Me2N C SeR

Se Me2N C SR

R = aryl, alkyl 51–95%

R = aryl, alkyl 66–74%

Scheme 12

A general synthesis of O-alkylselenocarbamates involves a convenient one-pot procedure for the preparation of the key intermediate isoselenocyanates <1994T639> (Scheme 13). The reactions occur in high yield and can be used for the preparation of O-alkylselenocarbamates derived from primary, secondary, and tertiary alcohols. The reaction also proceeds in an intramolecular manner to afford the cyclic selenocarbamate 17 (Equation (17) <1997PS(120–121)335>. O H R N C H

i RNH2

ii

iii R N C Se

R N C

R = alkyl, aryl O i. EtO C H, reflux, 12 h

R1OK

ii. Ph3P, Et3N, CCl4, 70 °C; iii. Se, Et3N Se R1O C N R H

Scheme 13 OH

Et3N, THF +

NC

HN

Se 80%

O

ð17Þ Se 17

The first report of the preparation of selenotellurocarbamic esters has appeared <1996OM5753>. Treatment of an acylisoselenocyanate with excess alkyl tellurol affords the selenocarbonyl Te-alkyl urethane 18 in yields of 20–40% (Equation (18)). O

O

Se

THF N C Se

+

RTeH –80 °C 20–42%

N H 18

TeR

ð18Þ

582

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

An aryl selenocarbamate prepared from the aryl isoselenocyanate is an intermediate in the ‘‘dehydration’’ of the very sensitive -amino acid 19 <2003BMCL433> (Equation (19)). N C Se OH

i.

NO2, Bun P 3

ð19Þ H N

CO2Et t-BOC

H N

ii. H2O2

CO2Et t-BOC

90%

19

Chiral oxazolidine-2-selones have proved to be useful as derivatizing agents for nuclear magnetic resonance (NMR) determination of chirality due to the extraordinary sensitivity of the 77 Se chemical shift to the chemical environment. Details of the preparation of a variety of these compounds by directed metallation of readily available 2-oxazolines have been reported <1994JOC4977>. (4S,5R)-4-methyl-5-phenyl-oxazolidin-2-selone 20 has proved to be particularly useful for determination of chirality <1994TA1627, 1995TA833, 1995JOC5540, 1996CC1125, 2002TA835>. The rapid reaction of this compound with an acid chloride or with an acid in the presence of a coupling reagent affords chiral oxazolidine-2-selones suitable for NMR analysis (Scheme 14) <1994TA1627, 1994TL1329, 1999JA10478>.

N

i. LHMDS ii. Se iii. Citric acid

O

Me

Se HN

Ph

O

Me

i, ii

BOC

H3C N HH*

O

Se N

O

Me

Ph

Ph

20 H CH3 N C * CO2H ii. DCC, DMAP i. BOC H

Scheme 14

Interesting ‘‘non-Evans’’ stereoselectivity has also been noted in aldol reactions of the readily prepared N-acyl oxazolidine-2-selones 21 (Scheme 15) <2000JA386>. This stereoselectivity and the above-mentioned sensitivity of the Se chemical shift to remote stereochemical centers in this heterocyclic system have been explained by unusual CH Se¼C interactions which have been detected spectroscopically <2000AG(E)3067>. Se

O N

O

i–iii

N R

R1

O

Se

OH O iv

R3

2

N

O

R2 R1 21

R1 v 98%

i. LiHMDS, –78 °C; ii. Se; iii. R1CH2COCl; iv. R3CHO-TiCl4; v. LiBH4

OH R3

OH R2

Scheme 15

A convenient conversion of the thiocarbonyl group of a thiocarbamate to the corresponding selenocarbonyl moiety involves treatment of the thiocarbonyl compound with triethyl orthoformate and boron trifluoride etherate followed by addition of sodium hydrogen selenide (Equations (20)–(22)) <1995JA8528, 1998S1442, 2002TL3879, 2002JCS(P1)1568> (cf. Section 6.19.3.2, Scheme 4).

583

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group R2

i. BF3-ether, HC(OEt)3, CHCl3 ii. NaHSe, EtOH

S

R2

S

S R

Se

N R1

2

2

79–96%

R

N R1

ð20Þ

R1 = Me, Ph R2 = CO2Me, CN R N

EtO2C

EtO2C

i. BF3–ether, HC(OEt)3 reflux

R N Se

S ii. NaSeH, EtOH, rt

S

Me

Me

S

ð21Þ

R = CH3, CH2CO2Et Me

Me N

i. BF3–ether, HC(OEt)3 reflux

N

ii. NaSeH, EtOH, rt

Se

S

ð22Þ

Se

Se

95%

Alkylation followed by hydrogen selenide treatment also provides a route to selenocarbamates from the corresponding thiocarbonyl compounds (Equation (23)) <1996PJC1124, 1999ACS861>. The alkylation–hydrogen selenide procedure can also be carried out starting from imines <1999PJC1315>. R1

O R2

N

ii. H2Se

S

S

O

R1

i. Me2SO4

R2

N S

Se

ð23Þ

R1 = alkyl, R2 = Ph, PhCH=CH yields 18–78%

Treatment of methyl thiocyanate with HCl affords the iminium salt which upon treatment with lithium aluminum hydrogen selenide affords the corresponding thioselenocarbamate (Equation (24)) <2001TL6333>. Se CH3 S C NH2

i. HCl, THF, 0 °C CH3 S C N

ð24Þ

ii. LiAlHSeH 51%

Bis(N,N-dialkylselenocarbamoyl)triselenides 22 can be prepared by reaction of chloroform (or sodium trichloroacetate) with secondary amines and elemental selenium in hexamethylphosphoramide (HMPA) in the presence of sodium hydride (Equation (25)) <1994CL2105, 1996BCJ2235>. Tetra-substituted selenoureas are also formed in this reaction, but the amounts of selenoureas formed can be controlled by temperature and the number of equivalents of amine used (cf. Section 6.19.4.1, Equation (28)). Et2NH

+

Se

Se

NaH, CHCl3, rt Et2N

Se Se

46%

Se Se

ð25Þ

NEt2

22

N,N-Dimethylformamide dimethylacetal reacts with elemental selenium to give a mixture of methyl N,N-dimethylselenocarbamate and the isomeric Se-methyl carbamate (Equation (26)) <1996JPR403>. Se (MeO)2CHNMe2 + Se

O

Xylene, reflux Me2N

O 22%

Me

+

Me2N

Se 33%

Me

ð26Þ

584 6.19.4

6.19.4.1

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) Selenoureas (R2N)2C¼Se

Selenoureas remain the most widely documented selenocarbonyl compounds. Thioureas can be converted to selenoureas by alkylation followed by careful displacement using sodium hydrogen selenide. Reactions of isoselenocyanates with amines, addition of hydrogen selenide to carbodiimides, and displacements of activated vinyl halides by selenourea also provide convenient general routes to selenoureas <1995COFGT(6)587>. Reactions of isoselenocyanates with amines continue to provide one of the most convenient routes to selenoureas (Equation (27)) <1997JIC161>. N

C

Se +

H H N C N CH2R Se

H2NCH2R

ð27Þ

80–92%

Treatment of N,N-dimethylselenocarbamoyl chloride (Section 6.19.2.2) with secondary or primary amines proves a convenient route to N,N-dimethylamino-substituted selenoureas. Extension of this method to the preparation of other N,N-disubstituted selenocarbamoyl chlorides should make this a very useful general method for the preparation of di-, tri-, and tetrasubstituted selenoureas (Equation (28)) <2002JOC1008>. Se Me2N C Cl

R1

Se R1 Me2N C N R

rt N H

R R,

R1 = alkyl,

ð28Þ

75–95%

R1 = alkyl, R = H, 27–55%

N,N-Disubstituted selenoureas can be prepared in very good yields by treatment of N,Ndialkylaminocyanamides with HCl followed by treatment with lithium aluminum dihydrogen selenide (Scheme 16) <2001TL6333>. They can also be prepared by the direct reaction of the corresponding cyanamides with highly toxic gaseous hydrogen selenide generated from aluminum selenide in the presence of sulfuric acid <1999PS(152)169>. R1 N C N

HCl, THF, 0 °C

R

R1

+

N C NH2 R Cl

–

Cl

LiAlHSeH

R1

70–91%

R

Se N C NH2

Scheme 16

N,N0 -Disubstituted selenoureas can be similarly prepared from the corresponding carbodiimides by reaction with hydrogen chloride followed by treatment with lithium aluminum dihydrogen selenide (Scheme 17) <2002SC3075>. This procedure avoids many of the problems associated with direct addition of hydrogen selenide.

RN C NR'

i

Cl RHN C NR'

ii

Se RHN C NHR'

56–93% i. HCl, rt, 4 h; ii. LiAlHSeH, 0 °C, 2 h

Scheme 17

Reactions of primary or secondary amines with triethyl orthoformate and selenium at elevated temperatures in a sealed vessel directly affords the corresponding selenoureas (Equation (29)) <2003TL1295>. Both cyclic and acyclic selenoureas can be prepared using this method.

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group R NH

R N

i

+

(EtO)3CH

Se 39–95%

NH R

585

N R

ð29Þ

R = Me, Et, But i. Se, 180–190 °, 8 h, sealed vessel

Simple tetra-substituted selenoureas can be prepared by reaction of sodium trichloroacetate (or chloroform) with secondary amines and elemental selenium in HMPA in the presence of sodium hydride (Equation (30)) <1994CL2105, 1996BCJ2235>. Bis-(N,N-dialkylselenocarbamoyl) triselenides are also formed in the reaction, but the amount of these formed can be controlled by varying the temperature and the amount of amine used in the reaction (cf. Section 6.19.3.5, Equation (25)). R1 N R2

NaH, HMPA Cl3CCO2Na

+

R1R2NH

Se

+ Se

N R1 R2

20–65% 1 2 R , R = Et 1 R , R2 = Bun

ð30Þ

1 2 R , R = –(CH2)5–

Since 1994, three selenating agents have been used for the preparation of simple acyclic selenoureas. Bis-trimethylsilylselenide reacts with N,N,N0 ,N0 -tetramethylurea in the presence of boron trifluoride etherate to afford the corresponding selenourea in good yield (Equation (31)) <1994BCJ876>. Monoselenophosphate reacts with cyanoguanidine to afford the corresponding selenocarbonyl compound in excellent yield (Equation (32)) <2001S1308>. A selenium analog of the widely used sulfurbased Lawesson reagent converts N,N0 -diethylurea to the corresponding selenourea in modest yield, however, the reaction was not successful in the case of N,N0 -diphenylurea <2001T5949>. (Me3Si)2Se, BF3·OEt2

O Me2N

Se Me2N

NMe2

ð31Þ

NMe2

64% H2PO4– H MeOH, H2O, H2PO3Se–

NH H H 2N C N C N

N H2N C

H Se H N C NH2

ð32Þ

94%

Hydroxyimidoyl chlorides can be converted to selenoureas in moderate yield via intermediate nitrile oxides 23 and isoselenocyanate intermediates (Scheme 18) <1999JOC6473>. OH N Cl

C N O–

i

CH3

CH3 23 Se

i. Et3N, THF, 25 °C; ii. 0 °C, THF, R

H N CH3

H N Se

R1

NH2

R1NH2 46–78%

Scheme 18

ii

N C Se CH3

586

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

A number of aromatic acyl selenoureidonitriles and esters have been prepared by reaction of the corresponding amines with an acyl isoselenocyanate (Equation (33)) <1997MI135, 1999CCC1673>. These compounds can be readily cyclized to the corresponding fused seleniumcontaining heterocycles <2000MI37>. R

R

O + Ar

NH2

S

N C Se

72–96%

S

Se O H N C N C Ar H

ð33Þ

R = CN, CO2Et

Reactions of in situ-generated acyl isoselenocyanates with aniline derivatives afford N-acyl-selenoureas in good yield (Scheme 19) <1994MI42>. Aliphatic amines react similarly <2000HCA539>. Related reactions also occur with N-phenylimidoyl isoselenocyanates (Scheme 20) <2000HCA1576> and N-benzylbenzimidoyl isoselenocyanates <2002HCA1102>. Primary amines can also be used in the latter reactions, but significantly lower yields were obtained using ammonia.

O Ar C Cl

O Ar C N C Se

Acetone KSeCN

Ar'NH2 71–83%

Se O Ar C NH NHAr'

Scheme 19

O Ar

N H

Ph

N

SOCl2 Ar

Ph Cl

i >98% HN Ar

Ph R2NH

N

R2N

Se

74–97% Ar

N

Ph N C Se

i. KSeCN, acetone R = alkyl, aryl, H

Scheme 20

Reaction of isonitriles with amines in the presence of 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) provides a convenient preparation of selenoureas, which can be readily converted by oxygen to the corresponding carbodiimides (Equation (34)) <1999SL75>. +

R N C–

R1NH2

i

Se H H R N C N R1

ii

RN C NR1

ð34Þ

i. Se, DBU, reflux, 1 h; ii. O2, reflux

Similarly 75Se-labeled dicyclohexylselenourea has been prepared in 90% radiochemical yield by the reaction of cyclohexylisonitrile and cyclohexylamine in the presence of 75Se (Equation (35)) <2001MI140>. Labeled dicyclohexylselenourea can also be prepared directly by addition of labeled hydrogen selenide to the corresponding carbodiimide <2001MI578> (Scheme 21). The resulting labeled selenourea is a useful precursor in the preparation of 75Se-labeled selenides. A polymerbound selenourea could also be prepared from the corresponding carbodiimide (Equation (36)).

587

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group NC

75Se

NH2

75

Sen

+

N H

Benzene, reflux

ð35Þ

N H

90% radiochemical yield

75Se

+

N C N

H275Se

N H

N H

NHBOC i, ii, iii i.Br

CO2Et +–

ii. Bun4N iii. MeI

OH

CO2Et Me

75Se

NHBOC

Scheme 21

75Se

N C N

+

ð36Þ

H275Se

N H

N H

A novel approach to the preparation of heterocyclic selenoureas involves direct reaction of stabilized cyclic carbenes with elemental selenium. The intermediate carbene 24 can be prepared by reaction of 2,20 -bipyridine with a triphenylarsonium salt, followed by bromide exchange and base treatment. The resulting carbene is stable for several hours at 30 C, but can be trapped by elemental selenium affording the selenourea in high yield (Scheme 22). This selenourea can be directly prepared in 87% yield in a ‘‘one-pot’’ reaction without isolation of the carbene <1998AG(E)344, 2000EJIC1935>. The reaction of other stabilized carbenes with selenium also afford selenoureas (Equation (37)) <1996LA2019>.

CH3CN, reflux

+

N N

+ Ph3As

Bu4NBr

OTf

OTf

–Ph3 As

N

N

+

+

H

H

N + N 2OTf

–

Br

H KOtBu, –30 °C, THF

Se N

N

N

87%

N

Se 24

Scheme 22

Ph N N Ph

Ph Se, toluene, reflux

N

N N Ph

Ph

Se

N Ph

ð37Þ

588

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

Reaction of a series of electron-rich tetraalkylaminoethylenes with elemental selenium at elevated temperature affords the corresponding selenoureas in excellent yields, presumably via intermediate stable carbenes (Equation (38)) <1996AF1154>. Me Me N N

Se, toluene, reflux

Me N

96%

N Me

ð38Þ

Se N Me

6.19.4.2

N Me

Other Cyclic N(C¼Se)N Compounds

Traditional methods for the preparation of selenopyrimidines and selenopurines using selenourea continue to prove useful in the preparation of novel selenium analogs of biologically important compounds. Condensation of selenourea with ethyl 3-keto-hexanoate afforded propylselenouracil 25 the selenium analog of the widely used antithyroid drug 6-propyl-2-thiouracil (PTU) (Equation (39)) <1994OPP682>. O

O

Se +

OEt

H2N

H N

KOH, H2O

Se NH

NH2

ð39Þ

O 25

The 2- and 4-selenopyrimidine nucleosides have also been prepared via displacement reactions using selenourea and sodium hydrogen selenide (Schemes 23 and 24) <1999MI635>. Details of the introduction of selenium into selenoguanosine derivatives using selenourea have also been reported <1994JMC3561>. O RO

O

N

Cl RO

NH

O

i

N

O RO

Se RO

N

O

ii

N

O

X

RO

a. R = Bz, X = OBz b. R = p -Tol, X = H

NH O

X

RO

a. R = Bz, X = OBz b. R = p -Tol, X = H

X

a. R = H, X = OH b. R = H, X = H

i. SOCl2, DMF, CHCl3; ii. (NH2)2C=Se or NaHSe, MeOH or EtOH, 90 °C, N2

Scheme 23 O HN O

Cl F

i

N

N H

Cl

NH2

NH2 F

ii

F

N Cl

N

iii

F

N Se

N

N H

iv F

F NH2

NH2 HO

O

N

N

BzO v

O

N Se

Se HO

OH

N

BzO

OBz 90 °C, N2

i. POCl3; ii. aq. NH3, iii. NaHSe, n -BuOH, Ar; iv. BSTFA, MeCN, SnCl4, rt, 2 h; v. NH3, MeOH

Scheme 24

589

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group

The 2-selenoxoquinazoline derivative 26 can be conveniently prepared via cyclization of 2-isoselenocyanatobenzonitrile using hydrazine hydrate (Scheme 25) <1995PHA21>.

NaHSe, Na2CO3

CN N

N C Se

81%

CCl2

NH

NH2NH2, H2O

CN

N

72%

NH2

N H

Se

26

Scheme 25

The reaction of 5-aminoimidazole-4-carbonitrile with n-butylisoselenocyanate affords 27. Reaction with benzhydrylisoselenocyanate takes a very different course yielding the 1-selenopurine 28 (Scheme 26) <1995H47>. NH Bun N C Se

Bun

N

N

50 °C, 16 h Se

N H

N H

NC

N

27

H2N

N H

Se

H N

Ph Ph

Ph

50 °C, 16 h N C Se

N

Se Ph

Ph Ph

N H

N

N H

28

Scheme 26

Acyl selenoureidocarbonitrile 29, readily prepared by reaction of the corresponding nitrile with an acyl isoselenocyanate (Section 6.19.4.1, Equation (33)) can be readily cyclized to the corresponding fused selenopyrimidine 30 (Equation (40)) <1999CCC1673>. It is interesting that very slight structural changes can lead to the tautomeric selenol form 31 being observed as the exclusive product of this reaction (Equation (41)). NH2

CN S

KOH, MeOH, heat N

Se O H N C N C Ph H

S

N H

29

CN S

Se O H N C N C Ph H

Se

ð40Þ

30

H2N KOH, MeOH, heat

N N

S

SeH

ð41Þ

31

The reaction of the aryl isoselenocyanate with the heterocyclic thiourea provides a convenient route to a number of interesting heterocyclic selenoureas, including the hypervalent sulfurcontaining selone 32 and -diselone 33 (Scheme 27) <2002JHC189>.

590

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group Me

Me N S S

+

N

Ar

N C Se

S

95%

N

N N

Ar = 4-CH3OC6H4

Se

N

N

S

N

Ar

N

Se

32

170 °C –Ar N C Se

–MeNCS 91%

Ar N S Se

Se Ar

Ar

N

170 °C Ar

N

S

N

N

N C Se

33

59%

Scheme 27

6.19.4.3

Telluroureas (R2N)2C¼Te

A series of stable cyclic telluroureas have been conveniently prepared in excellent yields by the reaction of the stable carbene imidazol-2-ylidenes 34 with elemental tellurium (Equation (42)) <1993CB2047, 1997JA12742>. The special stability of the 2-telluroimidazolines is probably due to the major resonance contributor 35. R1

R N

R1

N R

+

Te

THF, 0 °C

R1

R N

90–100%

R1

N R

Te

ð42Þ

R, R1= Me

34

R = Et, R1 = Me R = Pri , R1 = Me R = Mes, R1 = H R = Mes, R1 = Cl

R1

R N

R1

N R

R1 Te R1

R N – Te + N R 35

Reactions of electron-rich tetraaminoethylenes with tellurium also afford telluroureas (Equation (43)) <1996AF1154>. It is likely that this reaction and previously described preparations of telluroureas <1995COFGT(6)587> which required relatively vigorous conditions also proceeded via similar carbene intermediates. Me Me N N

Te

Me N Te

N Me

N Me

toluene, reflux 88%

ð43Þ

N Me

Another stable carbene approach to telluroureas parallels the previously described carbene route to selenoureas (cf. Section 6.9.4.1, Scheme 22). Treatment of the bromide salt 36 with base in the presence of tellurium affords the tellurourea in 87% yield (Equation (44)) <2000EJI1935>.

591

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group Te

KOtBu, THF N

+

N

N

–30 °C

N

N

87%

–

ð44Þ

Te

Br

H

N

36

Up to the year 2003, no acyclic telluroureas have been reported in the literature.

6.19.5

HYPERVALENT SELENOCARBONYL COMPOUNDS OF THE TYPE Se¼C(X)X0

The reaction of 1,3-dimethyl-4-imidazolin-2-selone with molecular iodine affords a stable hypervalent selenocarbonyl compound 1,3-dimethyl-4-imidazolin-2-ylium diiodoselanide 37 characterized by a linear ISeI arrangement of atoms (Equation (45)) <1994G445>. A similar linear BrSeBr arrangement was noted when the same imidazolin-selone was treated with bromine <1998EJI137>. When the 1,10 -bis(3-methyl-4-imidazolin-2-selone)methane 38 was treated with iodine a linear IISe structure (39) was observed <1994G445> in contrast to linear BrSeBr structures noted for other bis-halo adducts with other selenoureas (Equation (46)) <1998EJI137>. Me N

Me X N Se N X Me

CH2Cl2 Se

+

X2

N Me X = I, Br

ð45Þ

37

I2 Me

N

N

N

Se

N

Me

CH2Cl2

Me I

Se

N

N

N

I Se

38

N

Se

I

Me

ð46Þ

I

39

Hypervalent adducts of N-methylbenzothiazole-2-selone and related compounds show a fascinating variety of structural types <1999JCS(D)2219>. A ‘‘T-shaped’’ structure was noted for dibromide 40 <1999JCS(D)2845>. Aryltellurium halide adducts 41 and 42 of the same benzothiazole precursor have also been reported <1996ACS759, 2002PS(177)853>. Spectroscopic evidence for 1:1 selenocarbonyl–Cl2 adducts has also been reported <1999JCS(D)4245>. Br Br

S

S

Te Ph

S

Se

Se N Br Me

N Me

40

41

Se

Te

N Me

OCH3

Cl3 42

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594

Functions Containing a Selenocarbonyl or Tellurocarbonyl Group Biographical sketch

Lynn James Guziec was born in Long Beach, California; she studied at Russell Sage College, Troy, NY where she received her B.A., special honors in Chemistry, in 1979. She received her Ph.D. in 1988 from New Mexico State University under the direction of Frank Guziec, Jr. She remained as a College Professor at New Mexico State University until 1995. She has been working as an Assistant Professor at Southwestern University since 1996. In 1998 she received an M.Sc. in Biological Sciences from the University of Warwick, UK. Her interests include heterocycles, organosulfur and organoselenium compounds, as well as the synthesis of medicinal and anticancer compounds.

Frank Guziec was born in Chicago, he studied at Loyola University of Chicago where he received a B.S. (Honors) degree in 1968. He received his Ph.D. degree in 1972 at MIT under the direction of Professor J. C. Sheehan. He carried out postdoctoral work at Imperial College, London with Professor D. H. R. Barton, at MIT with H. G. Khorana, and at Wesleyan University with M. Tishler. He has served on the Chemistry faculties of Tufts University, New Mexico State University and is currently Dishman Professor of Science at Southwestern University. He carried out sabbatical research in the Pharmaceutical Sciences Department at DeMontfort University, Leicester, UK with L. Patterson under a Fulbright Fellowship and with H. Hiemstra at the University of Amsterdam. His scientific interests include the chemistry of organoselenium compounds, extrusion reactions, functionalizing deamination reactions, and sterically hindered molecules. Collaborating with his wife Lynn Guziec he is also involved in the design and synthesis of anticancer compounds.

# 2005, Elsevier Ltd. All Rights Reserved No part of this publication may be reproduced, stored in any retrieval system or transmitted in any form or by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers

Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 573–594

6.20 Functions Containing an Iminocarbonyl Group and at Least One Halogen; Also One Chalcogen and No Halogen T. L. GILCHRIST University of Liverpool, Liverpool, UK 6.20.1 INTRODUCTION 6.20.2 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 6.20.2.1 Iminocarbonyl Compounds with Two Similar Halogen Functions 6.20.2.1.1 Carbonimidic difluorides, F2C¼NR 6.20.2.1.2 Carbonimidic dichlorides, Cl2C¼NR 6.20.2.1.3 Carbonimidic dibromides, Br2C¼NR 6.20.2.2 Iminocarbonyl Compounds with Two Dissimilar Halogen Functions 6.20.2.3 Iminocarbonyl Halides with One Halogen and One Other Heteroatom Function 6.20.2.3.1 Iminocarbonyl chlorides with one other heteroatom function 6.20.3 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN (AND NO HALOGENS) 6.20.3.1 Iminocarbonyl Compounds with Two Similar Chalcogen Functions 6.20.3.1.1 Iminocarbonyl compounds with two oxygen functions 6.20.3.1.2 Iminocarbonyl compounds with two sulfur functions 6.20.3.1.3 Iminocarbonyl compounds with two selenium functions 6.20.3.2 Iminocarbonyl Compounds with Two Dissimilar Chalcogen Functions 6.20.3.2.1 Iminocarbonyl compounds with one oxygen and one sulfur function 6.20.3.2.2 Iminocarbonyl compounds with one oxygen or sulfur and one selenium function 6.20.3.3 Iminocarbonyl Compounds with One Chalcogen and One Other Heteroatom Function 6.20.3.3.1 Iminocarbonyl compounds with one oxygen and one nitrogen function 6.20.3.3.2 Iminocarbonyl compounds with one sulfur and one nitrogen function 6.20.3.3.3 Iminocarbonyl compounds with one selenium and one other heteroatom function

6.20.1

595 596 596 596 597 597 598 598 598 599 599 599 599 600 600 600 601 601 601 602 602

INTRODUCTION

This chapter covers methods of synthesis of a wide range of iminocarbonyl compounds that have two heteroatoms attached to the carbon of the iminocarbonyl function. Only a few new methods for the preparation of these compounds have been described since the earlier review (chapter 6.20 in <1995COFGT(6)601>). The new methods, and new examples of the more important general methods, are described here. 595

596 6.20.2

Functions Containing an Iminocarbonyl Group and at Least One Halogen FUNCTIONS CONTAINING AT LEAST ONE HALOGEN

6.20.2.1

Iminocarbonyl Compounds with Two Similar Halogen Functions

Compounds having the formula XYC¼NR (X,Y = halogen) are named as carbonimidic dihalides under the IUPAC nomenclature system. They are also commonly referred to as isocyanide dihalides or as iminocarbonyl dihalides in the literature. The most detailed review of methods of preparation of carbonimidic dihalides is by Ku¨hle <1983HOU(E4)522>. The majority of compounds of this type bear two similar halogen functions. The most common compounds of this class are carbonimidic dichlorides (X,Y = Cl) and several have been found as natural products in marine organisms; these include examples that have been described since the publication of COFGT (1995) <1999JNP1339, 2001JNP111, 2001JNP939>. The general methods available for compounds in this class remain those described in chapter 60.20.1.1 in <1995COFGT(6)601>; new examples of these methods and a few new specific methods are described in the following sections. There are no new reports of methods for dihaloiminium cations or for carbonimidic diiodides. 6.20.2.1.1

Carbonimidic difluorides, F2C¼NR

Methods for the preparation of carboimidic difluorides are those described in chapter 60.20.1.1.1 in <1995COFGT(6)601>. The most general of these methods are summarized briefly in Scheme 1. Further examples of the conversion of carbonimidic dichlorides into carbonimidic difluorides (method B) have been described <2001JFC(109)123>. A further illustration of method D is the preparation of perfluorinated carbonimidic difluorides by the dechlorination of the perhaloalkane 1 with a catalytic amount of trimethyltin chloride (Equation (1)) <1995AG(E)586>.

F F

KF or base NHR A

F

Cl

F NR B

Cl

F NR F

F2

+ NR

C F Cl

N(Cl)R D

F

Scheme 1

F

Cl

Me3SnCl, 25 °C

F

Quant.

F

N

Cl F

N N(CF3)2

N(CF3)2

ð1Þ

1

A new method for the preparation of N-(trifluoromethyl)carbonimidic difluoride 2 is the thermal decomposition of potassium perflluorodimethylaminoacetate (Equation (2)); compound 2 was obtained as the principal product, but it was not completely separated from by-products <1999JFC(95)161>. F K O2C

F

CF3 N CF3

270–280 °C

F

45%

F

N CF3 2

ð2Þ

Functions Containing an Iminocarbonyl Group and at Least One Halogen 6.20.2.1.2

597

Carbonimidic dichlorides, Cl2C¼NR

The most general methods for the preparation of carbonimidic dichlorides are summarized in Scheme 2. All these methods were described in chapter 60.20.1.1.2 in <1995COFGT(6)601>. A few publications that include some experimental detail have appeared with additional examples of some of these methods. Thus, some new N-arylcarbonimidic dichlorides have been prepared by the reaction of aryl isothiocyanates with chlorine (method A) <1997SC2645>. A new exchange reaction has been used to prepare 2-biphenylylcarbonimidic dichloride from the corresponding dibromide (Equation (3)) <1995CC2295>. Cl2 S

NR A Cl2 or SO2Cl2 NR B

Cl NR

SO2Cl2, SOCl2 O

Cl

(R = aryl ) NHR C RCl

Cl

N D

Scheme 2

Br

Cl

Ph

SO2Cl2, SnCl4

N Br

6.20.2.1.3

Ph N

ð3Þ

Cl

Carbonimidic dibromides, Br2C¼NR

The addition of bromine to isocyanides (Equation (4)) is the most general method for the preparation of carbonimidic dibromides. A wide range of isocyanides has been used and several new examples have been reported <1995CC2295, 1996CC41, 1996S975>. The reaction can be used as a method of protection of sensitive isocyanide functions since it can be reversed by reduction with triethyl phosphite or magnesium <1996CC41, 1996S975>. Br Br2

+

NR

ð4Þ

NR Br

The dibromooxime 3 has been prepared from glyoxylic acid aldoxime and bromine as described in chapter 60.20.1.1.3 in <1995COFGT(6)601>. The oxime 3 is important as a source of the nitrile oxide 4, a useful 1,3-dipole (Scheme 3). The reaction sequence is often carried out without isolation of the intermediate dibromooxime 3 <1994T7543, 1995LA619> but there is also a description of a further experimental procedure for its isolation <1997JHC345>. An analogous procedure has been used to generate carbonimidic dibromides (without HO2C

Br N OH

Br

+ – N O

Br

N OH 3

Scheme 3

4

598

Functions Containing an Iminocarbonyl Group and at Least One Halogen

isolation) from the benzylhydrazone <1994T7543> and the phenylhydrazone <1999TL2605> of glyoxylic acid.

6.20.2.2

Iminocarbonyl Compounds with Two Dissimilar Halogen Functions

No further advances in this area have occurred since the publication of chapter 6.20.1.2 in <1995COFGT(6)601>.

6.20.2.3

Iminocarbonyl Halides with One Halogen and One Other Heteroatom Function

There have been very few advances since the publication of chapter 6.20.1.3 in <1995COFGT(6)601>. The most general method of preparation of compounds of this type is the selective displacement of one halogen from the appropriate iminocarbonyl dihalides, the main difficulty being in limiting the displacement to a single halogen. Other approaches that have some generality are addition reactions to isocyano groups and (for chloro compounds) chlorination of precursors such as isothiocyanates, ureas, and thioureas. New examples of these reactions are mainly restricted to iminocarbonyl chlorides with a nitrogen function.

6.20.2.3.1

Iminocarbonyl chlorides with one other heteroatom function

The electrophilic addition of sulfenyl chlorides to isocyanides is a known method for the preparation of iminocarbonyl chlorides with a sulfur function. A specific extension of this method to a nitrogen species is the addition of N-chlorobenzotriazole to isocyanides, which leads to mixtures of N-1 substituted and N-2 substituted benzotriazoles 5 and 6 (Equation (5)) <2001JOC2854>. The method appears to have the potential of extension to other N-halo compounds.

N N

N N

NR

+

N

NR

Cl

70–93%

Cl

ð5Þ

N

NR

R = Ar, Bn, TsCH2, BtCH2

N

N

N

+

Cl

5

6

Carbonimidic chlorides that bear a nitrogen function have proved to be useful intermediates in various heterocyclic syntheses. Two recent examples that represent applications of known methods are illustrated in Scheme 4. A synthesis of 2,4-diaminoquinazolines makes use of X

X NMe2

Et2N

PCl5

NH O

Et2N

Me2NCN, TiCl4

N

X N

Cl

N

7

NEt2

Cl NMe2 Cl Cl N NH2

CN

8 N N

CN Cl NMe2

HCl (g)

Cl

N N

N NMe2 9

Scheme 4

599

Functions Containing an Iminocarbonyl Group and at Least One Halogen

the imidoyl chlorides 7 as key intermediates; they are prepared from N-aryl-N0 ,N0 -diethylureas by reaction with phosphorus pentachloride <1998H(48)319>. The reaction of primary amines with dichlorodimethyliminium chloride 8 is a known and efficient method for the preparation of dimethylamino substituted imidoyl chlorides and this method has been used in a synthesis of the pyrrolotriazine 9 <1996T3037>.

6.20.3

FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN (AND NO HALOGENS)

6.20.3.1

Iminocarbonyl Compounds with Two Similar Chalcogen Functions

6.20.3.1.1

Iminocarbonyl compounds with two oxygen functions

A general method for the preparation of compounds of this class (carbonimidic diesters) is the displacement of chloride from carbonimidic dichlorides by an excess of an alcohol or a phenol under basic conditions. A recent variation of this method that has been used to prepare the iminodioxolenes 10 is the cathodic reduction of diaryl-substituted 1,2-diketones in the presence of N-arylcarbonimidic dichlorides (Equation (6)) <1994TL2365, 1995T3641>. Otherwise, the methods of preparation of these diesters are as described in chapter 6.20.2.1.1 in <1995COFGT(6)601>. Ar1

O

Cl NAr

+ Ar 2

2e

O

Ar 2

O

NAr 3

Cl

O

Ar1

3

ð6Þ

10

6.20.3.1.2

Iminocarbonyl compounds with two sulfur functions

Carbonimidic dithioesters are usually prepared most conveniently by S-alkylation of dithiocarbamate salts or esters, which are in turn readily available from the reaction of primary amino compounds with carbon disulfide. Methods involving displacement of halide are relatively less used, but new examples of such reactions include routes to the sulfones 11 (R = Me or Ph) by displacement of bromide <1997JA5982, 1998CC1143>. The sulfur(II) substituent in compounds 11 can be oxidized by MCPBA to give the bis(sulfones) 12 (Scheme 5). The oxime 14 was prepared in high yield by a double displacement reaction of the sulfone functions of compound 13 by sodium methylmercaptide (Equation (7)) <1997JA5982>.

PhO2S NOTHP

RSNa 78–85%

Br

PhO2S

MCPBA

PhO2S

NOTHP

NOTHP

RS

RO2S 11

12

Scheme 5

O2 S

2 NaSMe

MeS

NOBn S O2 13

NOBn 92%

MeS 14

ð7Þ

600

Functions Containing an Iminocarbonyl Group and at Least One Halogen

6.20.3.1.3

Iminocarbonyl compounds with two selenium functions

There are no general methods for the preparation of this small class of compounds. An example of a preparation of an acyclic species from an isoselenocyanate is shown in Equation (8), but this method has no generality <1996T12165>. Most of the known compounds of this class are 2-iminodiselenoles; two examples of the preparation of these compounds are shown in Scheme 6 <1996ZOR1870, 2000CEJ1153>. BuSe N

Se

Me

N

ButLi, BuI

Me

Me

ButSe Me

31%

ð8Þ

Me

Me

Me

Me

KOBut

N N Se

Se

+

Se

NPh

NPh 53%

Se

I Me

I2, NH4OH

Se

Me

Se

NMe2 Se

Me

Se

Me

PF6

NMe2

Me

Se

Me

Se

NNMe2

NH

90%

I

Scheme 6

6.20.3.2

Iminocarbonyl Compounds with Two Dissimilar Chalcogen Functions

With the exceptions of the reactions detailed below the methods for the preparation of these compounds are as described in chapter 6.20.2.2 in <1995COFGT(6)601>.

6.20.3.2.1

Iminocarbonyl compounds with one oxygen and one sulfur function

Isothiocyanates are the most commonly used starting materials for the preparation of compounds of this class; an alkoxide is added to the isothiocyanate to give a salt that is then S-alkylated. Some new examples of this method, with sodium methoxide as the nucleophile, have been described <1995SC3973>. An example of the procedure in which tributyltin oxide is used as the base is shown in Scheme 7 <1997H(45)1913>. The dithiazolone 15 has been prepared by a related method involving one-pot N-acylation and S-thiolation of ethyl thiocarbamate <1996JOC6639>.

EtOH, (Bu3Sn)2O S

S

74%

TMS

S

ClS NH2

EtO

+

EtOTf

EtS

60%

EtO

NH

N EtO

Et3N

N TMS

S

O Cl

63%

O

S N EtO 15

Scheme 7

TMS

601

Functions Containing an Iminocarbonyl Group and at Least One Halogen

A new method for the preparation of 2-acetylimino-1,3-oxathiazoles is illustrated in Scheme 8. Reaction of the dicyano epoxide 16 with potassium thiocyanate and acetic anhydride gave the oxathioles 17; the five-membered ring is probably formed by intramolecular addition of a hydroxyl group to the CN triple bond, as shown <1993JCS(P1)351>. Ar

Ar O

SCN

Ar

S

SCN

NH

OH

NC

NC

CN

NC NC

CN

S

NC

O

NAc

42–69%

O

Ar Ac2O

16

17

Scheme 8

6.20.3.2.2

Iminocarbonyl compounds with one oxygen or sulfur and one selenium function

A few new compounds in this category have been prepared by methods analogous to those in the two preceding sections. The first 1,3-oxaselenoles 18, having structures analogous to the oxathioles 17 but with selenium in place of sulfur, were prepared by the method shown in Scheme 8 but with potassium selenocyanate as the nucleophile <1993JCS(P1)351>. 2-Phenylimino-1.3-thiaselenole 19 has been prepared in low yield by a method analogous to that in Scheme 6, from the reaction of phenyl isoselenocyanate with 1,2,3-thiadiazole (Equation (9)) <1996ZOR1870>. A displacement reaction analogous to that of Scheme 5 has been carried out using the sodium salt of benzeneselenol (NaSePh) to give the sulfone 20 <1998CC1143>.

N N

Se

+

KOBut

Se

12%

S

NPh

S

NPh

ð9Þ

19

Ar

PhSe

Se NAc

NC

O 18

6.20.3.3

N PhO2S

OTHP 20

Iminocarbonyl Compounds with One Chalcogen and One Other Heteroatom Function

With the exceptions described below, the general methods available for compounds in this class remain those described in chapter 60.20.2.3 in <1995COFGT(6)601>.

6.20.3.3.1

Iminocarbonyl compounds with one oxygen and one nitrogen function

Compounds of this class are commonly known as isoureas or as pseudoureas. A review of their methods of preparation and their properties has appeared <1995RCR929>. General methods for their preparation include addition of nucleophiles to the CN triple bond of cyanates or cyanamides, and addition–elimination reactions of other iminocarbonyl compounds. Two new examples of these two general approaches are shown below. The salt 21 was prepared from cyanamide by reaction with butanol and anhydrous 4-toluenesulfonic acid in anhydrous chloroform (Equation (10)) <1999JA5940>. Displacement by an amine of one phenoxy group from the activated iminocarbonate 22 gave the isourea 23 in good yield (Equation (11)) <2000HCA287>.

602

Functions Containing an Iminocarbonyl Group and at Least One Halogen H2N

BuOH, 4-TsOH anhyd. H2N

NH2 OTs

N 70%

ð10Þ

BuO 21

PhO +

NCN

NH2.HNO3

O2NO

PhO

Et3N

H N

O2NO

NCN

87%

22

6.20.3.3.2

ð11Þ

PhO 23

Iminocarbonyl compounds with one sulfur and one nitrogen function

Compounds of this type are commonly known as isothioureas. This large and mostly stable group of compounds can be prepared by a variety of methods, the most general of which is S-alkylation of thioureas. The thioureas can, in turn, be prepared by the addition of nitrogen nucleophiles to isothiocyanates. An example of this reaction sequence, through the intermediate thiourea 24 followed by S-methylation, is shown in Scheme 9 <1997H(45)1405>.

NH S

N

N TMS

S

N

MeI

NH TMS

N

97% (2 steps)

MeS

TMS

24

Scheme 9

Another method that is useful for isothioureas that bear an activating group on nitrogen is nucleophilic displacement from activated carbonimidic dithioesters. A new example of this method is the preparation of the iminothiazolidine ester 25 (Equation (12)) <2000SL33>.

CO2Et

MeS NCN

+

HS

Et3N

NH2.HCl

MeS

H N

EtO2C

NCN

95%

S

ð12Þ

25

6.20.3.3.3

Iminocarbonyl compounds with one selenium and one other heteroatom function

Compounds of this type are almost entirely restricted to those with a selenium and a nitrogen function, commonly known as isoselenoureas. As with isothioureas, the most general method for the preparation of such compounds is Se-alkylation of selenoureas. An example of this approach that has been used to prepare the selenazolone 26 is shown in Equation (13) <2002S195>.

N

Cl NH2

Se

Cl

+ O

Pyr, 0 °C

N

29%

Se

N

ð13Þ O

26

603

Functions Containing an Iminocarbonyl Group and at Least One Halogen

A related new approach to isoselenureas makes use of isocyanides as starting materials. The addition of a lithium dialkylamide and selenium to the isocyanide gave the lithium salts 27 which were then converted into isoselenoureas 28 by Se-alkylation with iodobutane (Scheme 10) <1997T12159>.

R1R2N Se + R1R2NLi +

NR3

NR3 LiSe 27

BuI

R1R2N NR3 BuSe 28

Scheme 10

REFERENCES 1983HOU(E4)522 1993JCS(P1)351 1994T7543

E. Ku¨hle, Methoden Org. Chem. (Houben-Weyl) 1983, E4, 522. A. M. Le Mare´chal, A. Robert, I. Leban, J. Chem. Soc., Perkin Trans. 1 1993, 351–356. K. K. Bach, H. R. Elseedi, H. M. Jensen, H. B. Nielsen, I. Thomsen, K. B. G. Torssell, Tetrahedron 1994, 50, 7543–7556. 1994TL2365 A. Guirado, A. Zapata, J. Galvez, Tetrahedron Lett. 1994, 35, 2365–2368. 1995AG(E)586 B. Krumm, A. Vij, R. J. Kirchmeier, J. M. Shreeve, H. Oberhammer, Angew. Chem., Int. Ed. Engl. 1995, 34, 586–588. 1995CC2295 K. S. Currie, G. Tennant, Chem. Commun. 1995, 2295–2296. 1995COFGT(6)601 T. L. Gilchrist, Functions containing an iminocarbonyl group and at least one halogen; also one chalcogen and no halogen, in Comprehensive Organic Functional Group Transformations, A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Eds., Elsevier, Oxford, 1995, Vol. 6, pp. 601–638. 1995LA619 A. G. Griesbeck, J. Hirt, K. Peters, E. M. Peters, H. G. Von Schnering, Liebigs Ann. Chem. 1995, 619–623. 1995RCR929 A. A. Bakibayev, V. V. Shtrykova, Russ. Chem. Rev. (Engl. Transl.) 1995, 64, 929. 1995SC3973 J. Bernat, P. Kristian, J. Imrich, D. Mazagova, J. Cernak, T. Busova, J. Lipkowski, Synth. Commun. 1995, 25, 3973–3979. 1995T3641 A. Guirado, A. Zapata, P. G. Jones, Tetrahedron 1995, 51, 3641–3654. 1996CC41 J. E. Baldwin, R. M. Adlington, I. A. O’Neil, A. T. Russell, M. L. Smith, Chem. Commun. 1996, 41–42. 1996JOC6639 L. Chen, T. R. Thompson, R. P. Hammer, G. Barany, J. Org. Chem. 1996, 61, 6639–6645. 1996S975 M. Bergemann, R. Neidlein, Synthesis 1996, 975–980. 1996T3037 J. M. Quintela, M. J. Moreira, C. Peinador, Tetrahedron 1996, 52, 3037–3048. 1996T12165 H. Maeda, N. Kambe, N. Sonoda, S. Fujiwara, T. Shin-Ike, Tetrahedron 1996, 52, 12165–12176. 1996ZOR1870 N. I. Zmitrovich, M. L. Petrov, Zh. Org. Khim. 1996, 32, 1870–1874. (Russ. J. Org. Chem. 1996, 32, 1812–1816). 1997H(45)1405 M. Oba, M. Yoshihara, K. Nishiyama, Heterocycles 1997, 45, 1405–1410. 1997H(45)1913 M. Oba, M. Yoshihara, J. Nagatsuka, K. Nishiyama, Heterocycles 1997, 45, 1913–1919. 1997JA5982 S. Kim, J. Y. Yoon, J. Am. Chem. Soc. 1997, 119, 5982–5983. 1997JHC345 R. N. Hanson, F. A. Mohamed, J. Heterocycl. Chem. 1997, 34, 345–348. 1997SC2645 J. A. C. Alves, R. A. W. Johnstone, Synth. Commun. 1997, 27, 2645–2650. 1997T12159 H. Maeda, T. Matsuya, N. Kambe, N. Sonoda, S. Fujiwara, T. Shin-Ike, Tetrahedron 1997, 53, 12159–12166. 1998CC1143 S. Kim, J. H. Cheong, Chem. Commun. 1998, 1143–1144. 1998H(48)319 W. Zielinski, A. Kudelko, E. M. Holt, Heterocycles 1998, 48, 319–328. 1999JA5940 R. A. Moss, L. A. Johnson, D. C. Merrer, G. E. Lee, J. Am. Chem. Soc. 1999, 121, 5940–5944. 1999JFC(95)161 M. Nishida, H. Fukaya, E. Hayashi, T. Abe, J. Fluorine Chem. 1999, 95, 161–165. 1999JNP1339 J. Tanaka, T. Higa, J. Nat. Prod. 1999, 62, 1339–1340. 1999TL2605 F. Foti, G. Grassi, F. Risitano, Tetrahedron Lett. 1999, 40, 2605–2606. 2000CEJ1153 A. Chesney, M. R. Bryce, S. Yoshida, I. F. Perepichka, Chem., Eur. J. 2000, 6, 1153–1159. 2000HCA287 M. Bertinaria, G. Sorba, C. Medana, C. Cena, M. Adami, G. Morini, C. Pozzoli, G. Coruzzi, A. Gasco, Helv. Chim. Acta 2000, 83, 287–299. 2000SL33 T. Tanaka, T. Azuma, X. Fang, S. Uchida, C. Iwata, T. Ishida, Y. In, N. Maezaki, Synlett 2000, 33–36. 2001JFC(109)123 V. A. Petrov, J. Fluorine Chem. 2001, 109, 123–128. 2001JNP111 M. Musman, J. Tanaka, T. Higa, J. Nat. Prod. 2001, 64, 111–113. 2001JNP939 S. Kehraus, G. M. Konig, A. D. Wright, J. Nat. Prod. 2001, 64, 939–941. 2001JOC2854 A. R. Katritzky, B. Rogovoy, C. Klein, H. Insuasty, V. Vvedensky, B. Insuasty, J. Org. Chem. 2001, 66, 2854–2857. 2002S195 M. Koketsu, F. Nada, H. Ishihara, Synthesis 2002, 195–198.

604

Functions Containing an Iminocarbonyl Group and at Least One Halogen Biographical sketch

Tom Gilchrist was born in York, England and studied chemistry at King’s College London, where he obtained his Ph.D. under the supervision of Charles Rees. He taught for many years at Liverpool University and retired from his post as Reader in 2002. He has published extensively on heterocyclic chemistry, with special interests in small ring compounds and cycloaddition reactions. He was a volume editor for COFGT (1995), and has also edited several volumes of Progress in Heterocyclic Chemistry with Gordon Gribble. He is joint editor, with Dick Storr, of Volume 13 of Science of Synthesis. Among his other publications is a textbook, Heterocyclic Chemistry.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 595–604

6.21 Functions Containing an Iminocarbonyl Group and Any Elements Other Than a Halogen or Chalcogen F. S´CZEWSKI Medical University of Gdan´sk, Gdan´sk, Poland 6.21.1 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS) 6.21.1.1 Iminocarbonyl Derivatives with Two Nitrogen Functions 6.21.1.1.1 N-Unsubstituted iminocarbonyl derivatives 6.21.1.1.2 N-Alkyl iminocarbonyl derivatives 6.21.1.1.3 N-Alkenyliminocarbonyl derivatives 6.21.1.1.4 N-Aryliminocarbonyl derivatives 6.21.1.1.5 N-Alkynyliminocarbonyl derivatives 6.21.1.1.6 N-Acyliminocarbonyl derivatives 6.21.1.1.7 N-Cyanoiminocarbonyl derivatives 6.21.1.1.8 N-Haloiminocarbonyl derivatives 6.21.1.1.9 N-Chalcogenoiminocarbonyl derivatives 6.21.1.1.10 N-Aminoiminocarbonyl derivatives 6.21.1.1.11 NP, NAs, NSb, and NBi iminocarbonyl derivatives 6.21.1.1.12 NSi, NGe, and NB iminocarbonyl derivatives 6.21.1.2 Iminocarbonyl Derivatives with One Nitrogen and One P, As, Sb, or Bi Function 6.21.1.2.1 N-Alkylimino derivatives with one P or As function 6.21.1.2.2 N-Arylimino derivatives with one P function 6.21.1.2.3 N-Acylimino derivatives with one P function 6.21.1.2.4 N-Haloiminocarbonyl derivatives with one P function 6.21.1.2.5 Hydrazono derivatives with one P function 6.21.1.2.6 Diazonium derivatives with one P function 6.21.1.2.7 N,N-Dialkyliminium derivatives with one P function 6.21.1.3 Iminocarbonyl Derivatives with One Nitrogen and One Metalloid Function 6.21.1.3.1 Silicon derivatives 6.21.1.3.2 Boron derivatives 6.21.1.4 Iminocarbonyl Derivatives with One Nitrogen and One Metal Function 6.21.1.4.1 Main metal derivatives 6.21.1.4.2 Transition metal derivatives 6.21.2 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P, As, Sb, OR Bi FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGEN FUNCTIONS) 6.21.2.1 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function and One P, As, Sb, or Bi Function 6.21.2.1.1 Bis(phosphino)iminocarbonyl derivatives 6.21.2.1.2 Bis(phosphinyl)iminocarbonyl derivatives 6.21.2.1.3 Iminocarbonyl derivatives with P function and one P, As, Sb, or Bi function

605

606 606 607 617 620 620 622 623 625 626 627 630 632 638 639 639 640 640 641 641 641 642 644 644 645 645 645 645 647 647 647 649 650

606

Functions Containing an Iminocarbonyl Group

6.21.2.1.4 Iminocarbonyl derivatives with one As, Sb, or Bi function and another As, Sb, or Bi function 6.21.2.2 Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function and One Si, Ge, or B Function 6.21.2.2.1 Iminocarbonyl derivatives with one P function and one Si, Ge, or B function 6.21.2.2.2 Iminocarbonyl derivatives with one As, Sb, or Bi function and one Si, Ge, or B function 6.21.2.3 Iminocarbonyl Derivatives with One P, As, Sb, and Bi Function and One Metal Function 6.21.2.3.1 Iminocarbonyl derivatives with one P function and one metal function 6.21.2.3.2 Iminocarbonyl derivatives with one As, Sb, and Bi function and one metal function 6.21.2.3.3 N-Unsubstituted iminocarbonyl derivatives 6.21.2.3.4 N-Alkyl- and N-aryliminocarbonyl derivatives 6.21.2.3.5 N-Haloiminocarbonyl derivatives 6.21.2.3.6 N-Aminoiminocarbonyl (diazomethane) derivatives 6.21.2.3.7 N-Silyliminocarbonyl derivatives 6.21.2.4 Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function 6.21.2.4.1 N-Alkyl- and N-aryliminocarbonyl derivatives 6.21.2.4.2 N-Aminoiminocarbonyl (diazomethane) derivatives 6.21.3 IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

6.21.1

650 650 650 651 652 652 653 653 653 654 654 654 655 655 655 655

IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGEN FUNCTION (AND NO HALOGEN OR CHALCOGEN FUNCTIONS)

6.21.1.1

Iminocarbonyl Derivatives with Two Nitrogen Functions

Iminocarbonyl derivatives (guanidines) can be obtained according to the routes depicted in Scheme 1. The following sections are ordered by type of substituents on the imino N2-atom.

NR2R3

MeI (or Me2SO4) or COCl2 or peracid

S NR4R5

X X = SMe, Cl, SO3H

NR2R3 + NR4R5

1

2

NH3, Alk-NH2

R1 N

NHR3

R Hal

NR4R5

O X = OMe, Cl, Cl2PO2

NR4R5

3

R1NH2

R1 N

2

NR2R3

MeI or COCl2 or POCl3

NR2R3

i. R2R3NH ii. R4R5NH

R1 N

Cl

NR4R5

4

Cl 6

5

R4R5NH

R4R5NH

R2 N C N R3

R1 N C N R3

7

8

Scheme 1

607

Functions Containing an Iminocarbonyl Group 6.21.1.1.1

N-Unsubstituted iminocarbonyl derivatives

Most methods for the preparation of N-unsubstituted iminocarbonyl derivatives are based on the reaction of primary or secondary amines with electrophilic precursors of the guanidine moiety. The guanylating precursor can be generated from various functions. Thiouronium salts of type 2 are generated by reacting thioureas 1 with trialkyl oxonium salts, alkyl halides, chlorinating agents, or peracids. Similarly, strong alkylating or chlorinating agents are also used for generation of electrophilic imino N2 centers from ureas 3. Compounds of type 2 react with amines in the classic reaction known as the Rathke guanidine synthesis. The direct reaction of 1-alkyl thiourea derivatives 1 with ammonia in the presence of zinc(II) or lead(II) salts gives rise to the formation of N-unsubstituted iminocarbonyl derivatives. Alternatively, 1,3-dialkyl guanidines can be prepared from activated carbamate-protected 1-alkyl urea and alkylamines in the presence of water-soluble carbodiimide followed by deprotection. Analogously, 1,3-di-t-butoxycarbonyl-thiourea is converted to 1-alkyl guanidines. Carboxamidines of type 2 bearing heteroaromatic leaving group (X = pyrazol-1-yl) and especially those N,N1-bisurethane protected (R1 = t-BOC or PhCH2OCO) are able to react with weak nucleophiles such as aromatic amines <1995COFGT(6)639>.

(i) N-Unsubstituted iminocarbonyl derivatives from thioureas Usually, the formation of guanidines from thioureas is achieved by application of coupling reagents such as mercury(II) salts, diisopropyl carbodiimide (DIC), 1-(3-dimethylaminopropyl)3-ethyl carbodiimide (EDCI) or Mukaiyama’s reagent leading to the intermediate formation of activated thiourea or carbodiimides. The following sections are ordered by type of the coupling reagent. Moreover, due to recent developments in the solid-phase synthesis, the solution-phase and solid-phase protocols will be discussed separately. (a) N-Unsubstituted iminocarbonyl derivatives from thioureas using mercury(II) salt as coupling reagent. Solution-phase methods. In 1993 Kim and co-workers reported a facile synthesis of bis(t-BOC)-protected guanidines of type 10 from thiourea 9 R2,R4 = H, R3,R5 = t-BOC promoted by HgCl2 <1993TL7677>. This method followed by deprotection with TFA offers an efficient synthesis of terminal guanidines (Equation (1)). R1R2NH

HgCl2

S

BOCN=C=NBOC BOCHN

NHBOC 9 H+

NBOC R1R2N

ð1Þ

NH R1R2N

NHBOC

NH2

10

A synthetic method for internal guanidines has also been developed, employing as the key step a nucleophilic substitution of bis(t-BOC)-protected terminal guanidines 10 <1995SL815>. The second substituent, R2, was introduced as an electrophile (formation of 11), and t-BOC-deprotection completed the synthesis of internal guanidines 12 (Equation (2)). An analogous phase-transfer-catalyzed alkylation of 10 has also occurred regioselectively at one of the carbamate nitrogens and the reaction proved to be tolerant to a wide range of functional groups on the guanidine including esters, amines, ketones, alcohols, and alkenes <2003JOC2300>. N-t-BOC R1R2N

N-t-BOC H 10

N-t-BOC

i or ii R1R2N

NH

TFA

N-t-BOC R3 11

R1, R2 = H, alkyl; R3 = alkyl, Bn; 50–95% i. NaH; ii. R3X, DMF, 0 °C to rt ii. R3X, Bu4N+ I–, KOH, DCM/H2O, rt, 4 h

R1R2N

NHR3 12

ð2Þ

608

Functions Containing an Iminocarbonyl Group

HgCl2-promoted guanylation was further studied with variously substituted thioureas 13 and the scope and limitations were presented by Ko and co-workers <1997T5291>. The process was found to be effective with thioureas containing at least one activating group. Such N-conjugated groups include N-carbonyl (acyl, alkoxycarbonyl, carbamoyl), N-cyano, N-sulfonyl, and N-aryl substituents (Equation (3)). S 1

R HN

NX

i 1

NHX

NR2R3

R HN

13

ð3Þ R1 = cyclohexyl, p-nitrophenyl; X = COR4 ; CN, SO2R4 R2R3NH = tetrahydroisoquinoline, aniline, p-methoxyaniline; 41–95% i. R2R3NH, HgCl2, Et3N, DMF, rt

A nickel-boride-promoted guanylation of amines with N,N0 -bis(t-BOC)thiourea 13 has also been described <2000USP6100428>. Solid-phase methods. A convenient solid-phase synthesis of ribonucleic guanidines 14 including abstraction of the sulfur atom from fluorenylmethoxycarbonyl (Fmoc)-protected thiourea by Hg2+ was described <2002T867> (Scheme 2).

O NH H2N O

LCAA-CPG

H N

O

N

O

NHMMTr

U

O

+ OTBs

TBsO

HgCl2, DMF, rt

HN

O

S

Hunig's base

NHFmoc U

NHMMTr O O

TBsO

HN

NFmoc HN O

LCAA-CPG

H N

O

NH N

O

OTBs

O 14 LCAA-CPG = long chain alkylamine-controlled pore glass (solid support) U = uracyl

Scheme 2

Mercury(II) oxide proved to be a coupling reagent capable of activating the thiourea sulfur fragment for substitution without elimination leading to the intermediate carbidiimides <2000OL3563>. Resin-bound thiourea 15 bearing two substituents at one of the nitrogen atoms reacted with ammonia and primary or secondary amines in the presence of HgO. The cleavage with 10% TFA in CH2Cl2 yielded guanidines of type 16 in the form of trifluoroacetate salts (Scheme 3).

609

Functions Containing an Iminocarbonyl Group NHR2

S N

O

N

NHR1

i. NaH, DMF

N

O

N

NR1

2

ii. R NCS, 2 h, rt Cl

Cl 15 R3N

R3NH2, MeCN

N

O

HgO, 12 h, 45 °C

N

NHR2 NR1

NR3 TFA, DCM

R1HN

NHR2

5 min, rt

Cl

16

R1 = alkyl, alkenyl, benzyl; R2 = alkyl, aryl; R3 = H, alkyl

Scheme 3

(b) N-Unsubstituted iminocarbonyl derivatives from thioureas using carbodiimide as coupling reagent. Solution-phase methods. Following the procedure elaborated by Poss and co-workers <1992TL5933> the water-soluble carbodiimide EDCI hydrochloride) was used for the synthesis of guanidinium derivatives 18 starting from carbamoyl isothiocyanates <2000JOC1566, 2002TL565>. The carbamoyl thiourea 17 obtained from ethoxycarbonyl isothiocyanate and hindered amines was coupled to a second amine in the presence of EDCI, forming 1,3-disubstituted and 1,1,3-trisubstituted guanidines through either stepwise or one-pot synthesis. The deprotection of the products was carried out using Me3SiBr under reflux in DMF followed by protonation with methanol, without cleaving of the functional groups (Scheme 4).

O Et

O

N

C

S

R1R2NH

S

Et DCM, THF

R3R4NH NR1 2

O

R

EDCl, Et3N, DCM

17

NR1R2

O Et

O

N

i, ii

NR3R4

72–79%

+ H2N

NR1R2 NR3R4

X

–

18

i. Me3SiBr, DMF, reflux; ii. Methanol

Scheme 4

Solid-phase methods. A practical solid-phase synthesis that uses Rink amide resin as an amine component in reacting with aromatic isothiocyanates and aliphatic amines to give 1,3-disubstituted guanidine of type 22 was described <2001TL2273>. The commercial Rink amide resin 19 was deprotected with 25% piperidine/DMF, and then treated with an isothiocyanate to give the resin-bound thiourea 20, which, in turn, was subjected to guanylation with an amine in the presence of DIC and Hu¨nig base (DIPEA) to give the resin-bound guanidine 21. The disubstituted guanidine 22 was cleaved off under mild Rink resin cleavage conditions (Scheme 5). A series of diverse guanidine compounds 25 (Scheme 6) were obtained based on a traceless linker approach to the solid-phase synthesis, utilizing resin-bound acyl isothiocyanate 23 <1999TL3999>. This precursor undergoes addition reactions with a variety of amines to form

610

Functions Containing an Iminocarbonyl Group S

i, ii NHFmoc 19

iii NHR1

N H 20 NR2R3

NR2R3

iv

NR1

N H

NR1

H2N 22

21

i. 25% Piperidine, DMF; ii. R1NCS, DCM, rt, 8 h; iii. R R NH, DIC, DIPEA, CHCl3, 50 °C, 2 days; iv. 25% TFA, DCM, rt, 1 h 2 3

Scheme 5

COOH

i. (COCl)2, DMF

O

ii. Bu4t N+ NCS–

NCS 23

O

R1NH2

NHR1

DMF

O

iii

NHR1

HN C

HN C NR2R3

S 24 NR2R3

iv

NHR1

HN 25

iii. R2R3NH, EDC, DIPEA, CHCl3 or DMF; iv. TFA, CHCl3, MeOH, 45–60 °C, 24–72 h

Scheme 6

the corresponding acyl thioureas 24. In the second step, a resin-bound guanidine formation is promoted through desulfurization with DIC. Cleavage of acyl guanidine is affected by treatment with TFA. A polymer-assisted synthesis (PAS) methodology to obtain guanidines 28, which combines advantages of traditional solution-phase chemistry with the application of polymeric reagents was developed as shown in Scheme 7 <2002TL7105>. Thus, N,N0 -bis(t-BOC)thiourea 9 is coupled with an amine with the use of polymer-supported carbodiimide 26. In order to remove a by-product (bis-(t-BOC)carbodiimide), PS-trisamine 27 was added as a scavenger. Further deprotection with TFA afforded terminal guanidines in very good yield. (c) N-Unsubstituted iminocarbonyl derivatives from thioureas using Mukaiyama’s reagent. Solution-phase methods. Mukaiyama’s reagent was examined as a replacement for toxic heavy metal salts to promote formation of carbodiimides from thioureas <1997JOC1540>. Primary and secondary aliphatic and aromatic amines subjected to the reaction with N,N0 -bis-(t-BOC)thiourea 9 and Mukaiyama’s reagent resulted in the formation of the corresponding N,N0 -bis-(t-BOC)guanidines of type 10 in 21–91% yields (Equation (4)).

611

Functions Containing an Iminocarbonyl Group

S BOCHN

N

i.

C

N

NR1R2

NR1R2 26

iii

NHBOC

BOCHN

NBOC 87–95%

NH2

+

9

R1R2NH

N

N H

ii.

H2N

NH 28

NH2 27

iii. 25% TFA in DCM

Scheme 7

N+ Me

S t-BOCHN

NH-t-BOC

Cl

NR1R2 I– t-BOCHN

R1R2NH, DMF

9

N-t-BOC

ð4Þ

10

R1 = H, alkyl, R2 = alkyl, aryl

Solid-phase methods. An interesting strategy for generating a wide variety of guanidines 32 by solid-phase synthesis was developed by Josey and co-workers <1998TL5899>. In one-pot, thiourea was deprotonated with 2 equiv. of sodium hydride, treated with the carbonylimidazole resin 29, and then capped with t-butyl dicarbonate to afford 30. Coupling of the thiourea 30 with primary and secondary amines in the presence of Mukaiyama’s reagent afforded the desired products 31 in good yields (Scheme 8).

O O

O

i, ii N

O

N

29

S N H

ArR1NH

BOC

N H

Mukaiyama’s reagent

30

O

Pr3i SiH

NArR1

O N H

NBOC

TFA, DCM

NArR1 H2N

31

NH 32

i. NaH, thiourea, THF; ii. (BOC)2O, THF

Scheme 8

(ii) N-Unsubstituted iminocarbonyl derivatives from isothioureas Solution-phase methods. Bis-(t-BOC)-protected guanidines 34 were obtained in 77–89% yields by treatment of the commercially available N,N0 -bis-BOC-S-methyl thiourea 33 with hindered aliphatic and aromatic amines in the presence of HgCl2 <2000SC2933>. This protocol can be used for the preparation of monoaryl internal guanidines (Equation (5)).

612

Functions Containing an Iminocarbonyl Group

SMe

SMe CH2Br

t-BOCHN

N-t-BOC

t-BOCN i

33

HN

NH2 N-t-BOC

t-BOCN

i

N-t-BOC

ð5Þ

ii

34

i. KOH, TBA, toluene, 60 °C, 4 h; ii. HgCl2, Et3N, DMF, rt to 60 °C

Solid-phase methods. 1,3-Disubstituted guanidines 37 can also be prepared from isothioureas on the solid phase <1998TL5701>. The reaction of Merrifield resin-bound bis-(t-BOC)thiopseudourea 35 with alcohols in the presence of Ph3P and diisopropyl azodicarboxylate (DIAD) gave N-alkylated resin-bound intermediate 36. The Mitsunobu reaction is relevant for most primary and secondary alcohols, including benzylic and allylic alcohols. The N-alkylated products were liberated from the resin as the bis-(t-BOC)-protected guanidines by exposure of 36 to excess methanolic NH3 in DMF. Deprotection with TFA gave the corresponding N,N0 -disubstituted guanidines of type 37 (Scheme 9).

N-t-BOC S

N-t-BOC

i

NH-t-BOC

S

35

NH

ii, iii

N-t-BOC R1

R2HN

36

NHR1 37

i. R1OH, PPh3, DIAD, THF, 20 h; ii. NH3, MeOH, DMF or R2NH2, DMF; iii. TFA, DCM R1 = alkyl, bn, allyl; R2 = H, alkyl, bn; 86–100%

Scheme 9

A similar approach has been utilized for a library synthesis of the analogs of the natural dipeptide antibiotic TAN 1057A,B <2002MI469>. 1,3-Disubstituted guanidines were synthesized using the Rink amide MBHA resin-bound methyl isothiourea 38 <1998TL2663>. Treatment with amines in DMSO afforded the corresponding guanidine derivative 39, which was cleaved from the resin with aqueous TFA to produce compounds 40 (Scheme 10).

H N

O

S

N H

NH

R1R2NH

CH3

DMSO, 70 °C

H N

O

NR1R2

N H

38

39 H N

95% TFA O H2O

40 R1 = H, alkyl; R2 = alkyl; 64–89%

Scheme 10

NH NR1R2

H2N

NH

613

Functions Containing an Iminocarbonyl Group (iii) N-Unsubstituted iminocarbonyl derivatives from 1-H-pyrazole-1-carboxamidine and related precursors

Solid-phase methods. Inspired by the previously described guanylating agent 1-H-pyrazole1-[N,N0 -bis-(t-BOC)]carboxamidine 41 <1993TL3389>, Patek and co-workers developed an acid labile linker for solid-phase synthesis of substituted guanidines <2000JCO370>. Attachment of the linker to the TentaGel–NH2 resin was accomplished using ‘‘acidic’’ coupling conditions to prevent direct displacement of pyrazole with TentaGel–NH2. Most primary and secondary aliphatic amines as well as arylamines reacted efficiently with 42, affording nearly quantitative conversion to 1,1-disubstituted guanidines of type 43 (Equation (6)). H N

O H N

O

O O

N

N

N-t-BOC

NH

i. R1R2NH, DMF, rt, 2 h R1R2N

NH2

ð6Þ

ii. TFA, DCM, H2O 43

42

4-Nitro-1-H-pyrazole-1-[N,N0 -bis-(t-BOC)]carboxamidine 44 (Figure 1) was also successfully used for guanylation of resin-bound dipeptides <1999TL53>. S t-BOCHN

SMe NH-t-BOC

t-BOCHN

N-t-BOC 33

9 O2N

N N t-BOCHN

N NBOC

41

N t-BOCHN

N

N N N-t-BOC

44

TsO–

NH2 H2N + 45

Figure 1

A comparison of guanylating agents N,N0 -bis-BOC-thiourea 9 and agent 0 1-H-pyrazole-1-[N,N -bis(t-BOC)]carboxamidine 41 was performed on a series of primary and secondary aliphatic and aromatic amines in both solution- and solid-phase resins <1997T6697>. Thiourea 9 performed well in solution and on solid-supported primary and secondary amines. Pyrazole 41 performed well in each case, except one aniline that failed to react. The relative reactivity of guanylating agents 9, 33, and 41 (Figure 1) was also investigated in the liquid-phase polymer-supported combinatorial synthesis of guanidines with piperazine and piperidine scaffolds <1998SL1423>. Benzotriazole methodology was further applied for the mild and efficient conversion of amines to guanidines <1995SC1173>. Benzotriazole-1-carboxamidinium tosylate 45 (Figure 1) was conveniently prepared by refluxing benzotriazole, cyanamide, and p-TsOH in 1,4-dioxane. The reaction with primary and secondary amines including aromatic amines in the presence of DIEA at room temperature afforded the corresponding guanidines in good yields.

(iv) N-Unsubstituted iminocarbonyl derivatives from urethane-protected guanidines and triflyl-diurethane-protected guanidines The new classes of urethane-protected guanylation reagents 46 <1997JOC4867>, 47, and 48 <1998JOC8432> as well as triflyl-protected 49 and 50 <1998JOC3804> (Figure 2) have been developed and utilized for the preparation of guanidines, guanidine-containing amino acids, and peptides in both solution and solid-phase. These compounds are stable, crystalline substances that can remain stable indefinitely if refrigerated.

614

Functions Containing an Iminocarbonyl Group Triurethane-protected guanidines: NH t-BOCHN

N-t-BOC

NH-t-BOC

t-BOCHN

46

NCbz

NH-t-BOC

CbzHN

47

NHCbz 48

Triflyl-diurethane-protected guanidines: NTf t-BOCHN

NTf

NH-t-BOC

CbzHN

NHCbz

49

50

Figure 2

Solution-phase methods. A series of arginine analogs 51 was synthesized via condensation of a primary or secondary alcohol with guanylating reagents 47 and 48, under Mitsunobu conditions to produce protected alkylated guanidines <1998JOC8432> (Equation (7)). A similar methodology was applied for guanylating agents 33 and 41 <1999SL193>. COOBn

CbzHN CbzHN

COOBn

47 , PPh3, DEAD

–

(CH2)n Nt-BOC

–

THF, reflux

ð7Þ

–

(CH2)n CH2OH

t-BOCN

NH-t-BOC 51

Guanylation of aliphatic and aromatic amines with bis-(BOC)- and bis-(Cbz)-protected triflylguanidines 49 and 50 gave the condensation products in 75–100% yields <1998JOC3804>. Combinatorial synthesis of N,N0 -bis-(t-BOC)-protected guanidines 52 based on the reaction of guanylating reagents 49 and 50 with soluble polymer-bound diamines has also been developed <1999BMCL1517>. This combinatorial liquid-phase methodology has proved to be a useful tool for constructing libraries containing diamine scaffolds (Equation (8)).

N O

NH2 (CH2)n

NO2 O

N-t-BOC NH-t-BOC NH N (CH2)n

49 MeO

ð8Þ

NO2 O

52

n = 1–3

Using the triflyl-diurethane-protected guanidines 49, and 50, guanidine-containing, biologically important molecules, e.g., guanadrel, guanoxan, guanethidine, and smirnovine, were synthesized <1999S1423>. Moreover, guanidinoglycosides <2000JOC9054> and a novel library of guanidineincorporated aminoglycoside antibiotics, guanidinopyranmycins was also synthesized using the reagent 49 <2002TL9255>. With regard to the discussion about syntheses of bis-urethane-protected guanidines, it is worth noting that a method of total deprotection of N,N0 -bis-(BOC)guanidines of type 10 has been developed <1997TL7865>. It was demonstrated that deprotection using SnCl4 proceeded smoothly in ethyl acetate at room temperature and led to the easily isolable guanidinium chlorides 53 (Equation (9)).

615

Functions Containing an Iminocarbonyl Group N-t-BOC R1R2N

NH

i, ii R1R2N

NH-t-BOC 10

.HCl

NH2 53

ð9Þ

R1, R2 = alkyl, aryl; 81–100% i. SnCl4 (4 equiv.), AcOEt, rt, 3 h; ii. MeOH

Solid-phase methods. The solid-support-linked guanylating reagent 55 consisting of a urethaneprotected triflyl guanidine attached to the resin via a carbamate linker was applied to the synthesis of guanidines from a variety of amines under mild conditions <2001OL1133>. t-BOC-guanidine was immobilized on p-nitrophenyl carbonate Wang resin to form the protected guanidine 54. Triflation of 54 resulted in the formation of resin-bound guanylating reagent 55. This reagent was used for the conversion of primary and secondary amines into resin-bound guanidines which were cleaved with TFA (Scheme 11).

N-t-BOC O

H2N

O O

O

NH2

N-t-BOC

O

NO2

HN NH2

54

i

ii, iii

O O

NH-t-BOC HN

55

NH 1 2

R RN

NH2

NSO2CF3

R1, R2 = alkyl; 33–100% i. Tf2O, Et3N, DCM, –78 °C to 0 °C; ii. R1R2NH, DCM, rt; iii. TFA, DCM

Scheme 11

Synthetic applications of diurethane-triflyl guanidines 49 and 50 were subject of a recent comprehensive review <2000PAC347>.

(v) N-Unsubstituted iminocarbonyl derivatives from di(azolyl)methanimines A mixture of di(benzotriazolyl)methanimines 56 and 57, obtained from the reaction of benzotriazole with cyanogen bromide, has been developed as a versatile guanylating reagent for the general synthesis of guanidines <2000JOC8080>. The sequential condensation of two amines with 56 and 57 proved to be insensitive to electronic and steric effects and allowed for the use of a wide diversity of amines. By this method it is now possible to obtain nonprotected tri- and tetrasubstituted guanidines 58 in high yields under neutral and mild conditions using an easy purification protocol (Scheme 12). A similar approach for synthesizing guanidine compounds was reported using di(imidazol-1-yl)methanimine <2002JOC7553>.

616

Functions Containing an Iminocarbonyl Group NH

NH

Bt1

1

Bt

Bt2

1

Bt

NH

R1R2NH

+

NR1R2

1

Bt

THF, rt, –BtH

57

56

NH

R3R4NH R1R2N

THF, ∆

BtH

+

NR1R2 58

N

N

Bt1 =

Bt 2 =

N

N

N

N

R1, R2 = H, alkyl, aryl; R3, R4 = H, Me, aryl

Scheme 12

(vi) N-Unsubstituted iminocarbonyl derivatives by miscellaneous methods 1,3-Disubstituted guanidines of type 59 were obtained upon solvolysis of 4,5-dihydro-2-thiazolamine hydrobromide and 5,6-dihydro-4H-1,3-thiazin-2-amine under the influence of aliphatic amines (Equation (10)) <2001CHE360>. NH

R1NH2

N (CH2)n

1

R HN

NH2

H2O

S

N H

(CH2)nSH

ð10Þ

59

n = 0, 1

R1 = Me, Et, CH2CH2OH

n = 1, 2

Amidinoureas of type 60 could be prepared by the reaction of an acyl-S-methyl thiourea with an amine followed by removal of the acyl groups (Scheme 13) <1996TL1945>. Alternatively, amidinothiourea 61 was produced by reacting dicyandiamide and sodium thiosulfate in acidic medium followed by neutralization with a base <1995OPP697>. This reaction involves three steps: (i) addition of two moles hydrogen chloride to dicyandiamide, (ii) addition of thiosulfuric acid and acidic hydrolysis, and (iii) release of the free amidinothiourea (61, gutimine) by treatment with a base (Scheme 14). CbzNCO

SMe H2N

NR1R2

O CbzHN

THF

NCbz

N H

NCbz

SMe

O CbzHN

N H

CbzHN 60

Et3N, DMF

NR1R2

O

i

NCbz

R1R2NH

N H

NH

R1 = H, alkyl; R2 = alkyl

i. H2 (60 psi), 20% Pd(OH) 2/C, 96–99%

Scheme 13

The synthesis of 11C-labeled guanidines 62 was described by Langstrom and co-workers <1996JA6868>. The conversion of the 11C-labeled cyanamide to 11C-labeled guanidines was achieved in both supercritical ammonia and aqueous ammonia solutions. The latter method gave low and

617

Functions Containing an Iminocarbonyl Group NH R1HN

+ NH2 NH

2HCl

R1HN

NHCN

R1HN

R1HN

N Cl H Cl–

+ NH2 S

H 2O

NH

Na2S2O3

N H NH

NH4OH R1HN

N NH2 H HSO– 4

NH

N H

SSO3H

S NH2

61 R1 = H, alkyl; 71–95%

Scheme 14

irreproducible yield as compared to performing the reactions in automated fluid synthesis (SFA) system. Using the SFA system designed for the use with supercritical ammonia, total radiochemical yields of 11C-labeled guanidines of 30–85% were obtained for the aromatic amines and 2–36% for the aliphatic amines (Equation (11)). RNH2

11CNBr

RNH11CN

NH3

RNH11CNH2

ð11Þ

NH R = alkyl, Ar

6.21.1.1.2

62

N-Alkyl iminocarbonyl derivatives

As shown in Scheme 1 preparation of N-alkyl guanidines may be carried out either directly from the reaction of thioureas with alkylamines in the presence of lead oxide or via S-alkyl isothiouronium salts (2, X = SMe, SEt) or isouronium salts (2, X = OMe, Cl, Cl2PO2). For the synthesis of sterically hindered pentaalkyl guanidines use of the reactive chlorformamidinium (Vilsmeier) salts is preferred. The bis-electrophilic guanidine precursor carbonimidic dichloride 6 upon reaction with 2 equiv. of the same amine or one each of two different amines gives tri-, tetra-, and pentaalkyl guanidines. Trisubstituted guanidines are also derived from the reaction of carbodiimides 8, obtained by dehydration or desulfurization of ureas or thioureas, with an amine. Reactions of alkyl cyanamides 7 with amines or amine salts give rise to the formation of N-alkylguanidines in high yields. The less common procedures involve either the reaction of complexes of mercury(II) chloride and t-butyl isocyanide with mono- and dialkylamines or lithium aluminum hydride reduction of various alkyl-substituted acyl guanidines (5, R1 = acyl) <1995COFGT(6)639>. During the 1990s, the following methods have been developed. Trichloroacetamides obtained via Overman [3,3] sigmatropic rearrangement are converted into N,N0 -dibenzyl-N0 -alkyl guanidines <1994CL2299>. The key step is the conversion of carbodiimide intermediate 63 into guanidine by rare earth triflates such as scandium or ytterbium trifluoromethane sulfonates (Scheme 15). An original sequence for solution and solid-phase synthesis of N,N0 ,N0 -trisubstituted guanidines of type 66 has been developed by Mioskowski and co-workers <2000CEJ4016>. The sequence involves as key intermediate a bis-electrophilic chlorothioformamidine 64 that undergoes smooth nucleophilic addition of a primary amine to afford the corresponding isothiourea. The guanidine 66 is then obtained by heating the isothiourea 65 in the presence of a primary amine in toluene (Scheme 16). In the analogous solid-phase synthesis, chloromethylpolystyrene (Merrifield resin) was used instead of benzyl chloride in the first step to give resin-bound dithiocarbonate. A library of di- and trisubstituted guanidines of type 70 was synthesized in the process termed ‘‘combinatorial synthesis on multivalent oligomeric support’’ (COSMOS) <1999TL4477>. The synthetic route consists of attaching thiourea onto the soluble tetravalent support 67, and conversion to the guanidine 68 in the presence of HgCl2 or via methyl isothiourea 69. Cleavage from the support in 20% TFA/DCM affords the guanidine 70 as the TFA salt (Scheme 17).

618

Functions Containing an Iminocarbonyl Group CCl3 CCl3CN R

HN

O i

O

HN

R

O BnNH2

CCl3

OH

HN

R

PPh3, CBr4 NHBn

N

Et3N

C

N

Bn

Sc(OTf)3 or Yb(OTf)3

R

R

N

BnNH2

63 i. Overman [3,3] sigmatropic rearrangement

Scheme 15

R1NH2

S

BnCl, CS2 R1HN

THF, rt

Bn

S

COCl2 S

Toluene, 60 °C

R1N

Bn Cl

64

R2NH2

Bn

S

Toluene, 60 °C

R1HN

R3NH2

N

Toluene, 100 °C

NR2

R1HN

65

R3 NHR2

66

Scheme 16

O HN

O (CH2)n S HN C 1 R

R1R2NH

HN

67

MeI, DMF

68

R2R3NH DMSO, 100 °C

O HN

(CH2)n NR1 HN C NR1R2

HgCl2, DMF

20% TFA/DCM

O (CH2)n SCH3 HN C NR1

H2N

69

(CH2)n NR1 HN C NR1R2 70

Scheme 17

HN R

Bn NHBn

619

Functions Containing an Iminocarbonyl Group

Another facile solid-phase synthesis of N,N0 ,N0 -substituted guanidines 75 from an immobilized amine component is depicted in Scheme 18. The resin-bound amine 71 is reacted with di-(2-pyridyl)thiocarbonate (DTP) to generate the isothiocyanate 72, which is then treated with aryl-/alkylamines to yield the corresponding resin-bound thiourea 73. Desulfurization of 73 is readily achieved by treatment with triphenylphosphine dichloride. Further reaction with aryl-/ alkylamines (formation of 74) followed by acidic cleavage with TFA yields N,N0 ,N0 -substituted guanidines 75 of excellent purity and in good yields <2002T1739>. O

O Wang

DPT (CH2)n

O

NH2

Wang

N

71

Wang

O

C

72

S

O

O

i

(CH2)n

O

DCM, 20 °C

(CH2)n S HN

ii

Wang

NR1R2

73

TFA

(CH2)n N NR3R4

O

DCM, 20 °C

NR1R2

74 O HO

(CH2)n N

NR3R4 NR1R2

75

i. R1R2NH, N-methyl-2-pyrrolidine, 20 °C; ii. R3R4NH, Ph3P, C2Cl6, dry THF, 20 °C

Scheme 18

The solid-phase library synthesis of trisubstituted guanidines of type 78 was accomplished by dehydration of ureas 76 with p-TsCl in pyridine to give solid-supported carbodiimides 77 followed by nucleophilic addition of amines and cleavage of the solid support with TFA (Scheme 19) <2002JCO167>. O

O p-TsCl

N R1

H N

NR2

N R1

Pyridine

N

O 76

C

NR2

77

O i. R3R4NH, DMSO ii. TFA, DCM

HN R1

H N

NR2 NR3R4

78

Scheme 19

As shown in Scheme 20, trisubstituted guanidines of type 80 were synthesized on solid support via aza-Wittig coupling of alkyliminophosphorane with an aryl or alkyl isothiocyanate to generate the corresponding solid-supported carbodiimide 79, which was then reacted with a primary or secondary amine <1997TL3377>.

620

Functions Containing an Iminocarbonyl Group Rink NH

N3

i, ii

Rink NH

O

N C N

O 79

NR1R2 iii, iv

H2N

HN N

O 80 i. PhNCS, THF; ii. PPh3, THF, 25 °C; iii. R1R2NH, DMSO, 25 °C; iv. TFA, H2O, 25 °C

Scheme 20

Preparation of differentially substituted guanidinium salts 81 from phosgenium salt by sequentially introducing secondary amines of markedly different reactivity was achieved as depicted in Scheme 21 <1997JOC4200>. Me + N Me

Cl Cl

Cl–

R1R2NH Et3N, DCM

Me + N Me

R3R4NH

Cl NR1R2

Et3N, DCM

Me + N Me

NR3R4

Cl–

NR1R2

81 NHR1R 2 NH(Et)2

NHR 3R 4

Pyrrolidine NH(Bn)2 Pyrrolidine NH(iPr)2 Pyrrolidine

Yield (%) 100 88 76

Scheme 21

6.21.1.1.3

N-Alkenyliminocarbonyl derivatives

Title compounds can be prepared by reacting Vilsmeier salts with ketone imines. Other methods involve the reaction of 1,1,3,3-tetramethyl guanidine with either acetylenedicarboxylate or isobutyraldehyde in the presence of catalytic amount of TsOH. No further advances have occurred in this area since publication of chapter 6.21.1.1.3 <1995COFGT(6)639>.

6.21.1.1.4

N-Aryliminocarbonyl derivatives

In general, the methods developed for syntheses of N-alkyl guanidines are also applicable to the preparation of N-aryliminocarbonyl derivatives. Thus, they can be obtained from amidinium salts 2 and urea derivatives 3, carbonimidic dichlorides 6, carbodiimides 8, and cyanamides 7 (Scheme 1) <1995COFGT(6)639>. Since then, however, several new methods for the preparation of this class of compounds have been developed.

(i) N-Aryliminocarbonyl derivatives from guanidines A straightforward synthetic approach to 6-guanidinopurines consists in the reaction of the 6-chloropurine derivatives with guanidine in DMF solution in the presence of DABCO as catalyst <2002T2985>. Similarly, the 4-O-triisopropylphenylsulfonyl (OTPS) thymidine can be guanylated directly in the presence of t-BuOK <1998TL547>.

621

Functions Containing an Iminocarbonyl Group (ii) N-Aryliminocarbonyl derivatives from thioureas

Ramadas and co-workers have developed several methods for direct syntheses of N-aryl-substituted guanidines 83 from N-arylthioureas 82. A rapid synthesis of N,N0 -di- and N,N0 ,N0 -trisubstituted guanidines can be achieved using copper sulfate–silica gel in the presence of an amine (Scheme 22, Method A). This method, however, suffers from disadvantages involving the unstable carbodiimide intermediate, use of costly copper salt, and the need for anhydrous conditions <1995TL2841>. Desulfurization of monoaryl and N,N0 -diarylthioureas with lac sulfur adsorbed on alumina followed by treatment with ammonia, diethylamine, or morpholine in the presence of triethanolamine provided the corresponding guanidines in 68–85% yields (Scheme 22, Method B). Hydrogen sulfide is effectively trapped by triethanolamine and, therefore, this process is bound to trigger commercial interest since pollution due to hydrogen sulfide is avoided <1996TL5161>. Oxidation of N,N0 -disubstituted thioureas using the previously unexploited reagents sodium metaperiodate and sodium chlorite in aqueous medium provides another facile and high-yielding route to N-aryl guanidines (Scheme 22, Method C) <1997SL1053>.

S R1HN

NR3R4

i, ii or iii, iv or v, vi

NHR2

R1N

82

NHR2 83

Method A: i. CuSO4, SiO2, TEA, THF; ii. R3R4NH, rt Method B: iii. Lac sulfur on alumina, triethanolamine; iv. R3R4NH, reflux Method C: v. NaIO4 or NaClO2; vi. R3R4NH, DMF–H2O, 80–85 °C R1

R2

R3

Ph Ph

Ph Ph

H CH3

Ph

Ph

CH3

Ph

Ph

C6H11

Ph Ph o -Tolyl

C2H5 Ph Ph Bn o -Tolyl C2H4OH

Ph

Ph

H

Ph

Ph

Et

Ph

Ph

Ph

C6H11

R4 H

Cond.

Yield (%)

Method

i, ii i, ii

90 78

A A

i, ii

75

A

i, ii

85

A

H

i, ii i, ii i, ii

90 80 75

A A A

H

iii, iv

85

B

Et

iii, iv

82

B

Morpholyl H

iii, iv

85

B

Morpholyl H

iii, iv

72

B

80

B

H CH3 H C2H5 C2H5

o -Tolyl

H

Morpholyl H

iii, iv

Ph

Ph

H

H

v, vi

76a, 80b

C

Ph

Ph

H

C6H11

v, vi

84a, 81b

C

a

b

C

a

b

Ph

Ph

H

Bn

v, vi

68 , 65

Ph

Ph

Et

Et

v, vi

76 , 80

C

Ph

Ph

C6H11

C6H11

v, vi

60a, 53b

C

a

NaIO4; b NaClO2.

Scheme 22

622

Functions Containing an Iminocarbonyl Group

(iii) N-Aryliminocarbonyl derivatives from isothioureas The reaction of a variety of anilines with a new N-methylguanylating agent 85 was reported to give the corresponding N-aryl guanidines 86 (Scheme 23). Formation of 85 entailed reaction of commercially available N-methyl thiourea with (BOC)2O to provide 84. Treatment of 84 with 2,4-dinitrofluorobenzene (Sanger’s reagent) furnished 85 in 86% yield <1996TL6815>.

NO2

O2N S t-BOCHN

S

Sanger’s reagent NMe-t-BOC

t-BOCN

N

i. ArNH2, Et3N NMe-t-BOC

H2N

ii. TFA

85

84

Ar NHMe

86

Scheme 23

Two solid-phase syntheses of libraries of N-aryl-substituted guanidinocarboxylic acids of type 89 were described <2000JCO276>. The first method involving trapping of solution-phase carbodiimides 87 by supported amines was used to produce N-aryl-N0 ,N0 -dialkyl derivatives 88 (Scheme 24). A limitation of this method was that the supported guanidines 88 tended to undergo an undesired intramolecular cyclization. The second solid-phase method (Scheme 25), featuring supported carbodiimides 90 and solution-phase amines was devised to prepare N,N0 -disubstituted and N,N0 ,N0 -trisubstituted guanidinocarboxylic acids 89. O S R1HN

NR2

Mukaiyama’s reagent NHR2

R1N

DCM, Et3N, 25 °C

Wang

C

(CH2)n NH2

87

84 O Wang

O

O

O

(CH2)n NHR2 HN

88

NR1

TFA, DCM

HO

(CH2)n NHR2 HN

89

NR1

25 °C, 1 h

R1= aryl, R2 = akyl; 53–96%

Scheme 24

(iv) N-Aryliminocarbonyl derivatives from carbodiimides Alkylation of the highly electron-deficient amines with N-trityl-protected carbodiimides 91 as shown in Scheme 26 leads to the formation of N,N0 -bis(aryl)guanidines 92 <1997TL6799>. The dehydration of N-trityl-N0 -arylureas to the corresponding carbodiimides 91 is achieved using the Burgess reagent.

6.21.1.1.5

N-Alkynyliminocarbonyl derivatives

The flash photolysis of phenylguanidinocyclopropenone leads to the formation of 2-(phenylethynyl)-1,1,3,3-tetramethyl guanidine as a transient intermediate which, in aqueous solution, is converted to an acyl guanidine <1995COFGT(6)639>.

623

Functions Containing an Iminocarbonyl Group R1

S O

N H

O

i O

N H

N

C

N R1

O 90

NR2R3 O

R1R2NH

O

25 °C, 10 h

N H

NR2R3 HO

TFA, DCM

N

N H

O

25 °C, 1 h

89

R1

N

R1

R2, R3 = alkyl; 56–94% i. Mukaiyama’s reagent, DCM, Et3N, 25 °C, 1 min

Scheme 25

O R1HN

NHR2

R1 = aryl, R2 = Tr

+

O + O Et3 N S N O –

DCM, 25 °C R1N

Burgess’ reagent

C

91

NHR1

i, ii, iii N

NR2

OMe

NH2

N

N 92

NH2 R1 = aryl

i. NaH, DMF; ii. 91; iii. 4N HCl, i -PrOH

Scheme 26

As shown in Scheme 27, the N-alkylideneynamines 94 can be prepared by the reaction of perchlorobutyne with tetramethyl guanidine (TMG). The trichlorovinyl group of 93 is transformed by buthyllithium and chlorosilane into a silylethinyl moiety <1988TL5355>.

6.21.1.1.6

N-Acyliminocarbonyl derivatives

Title compounds (5, R5 = acyl) are obtained by acylation of the free base of S-methyl isothiouronium salts (2; X = SMe) followed by treatment with monoalkylamines (Scheme 1). Condensation of unsubstituted or monosubstituted guanidines with acid esters gives monoacetylated products. The preparation of di- and trisubstituted guanidines can be accomplished using acid chlorides or anhydrides. Reactions of guanidines with N,N-dimethylthiocarbamoyl chloride or isothiocyanates give rise to the formation of corresponding 2-(thiocarbamoyl)guanidines. Similarly, 2-amidinoureas (5; R1 = ArNHCO) can be obtained by reacting guanidines with aryl isocyanates (ArNCO) or carbamoyl chlorides (ArNRCOCl) <1995COFGT(6)639>. The following methods have been developed since the publication of COFGT (1995).

624

Functions Containing an Iminocarbonyl Group Cl Cl

Cl

2TMG

C C C Cl C Cl

N(Me)2 C C C N C C N(Me)2 Cl

Cl

i. 2BuLi ii. ClSiMePh2

93

N(Me)2 MePh2Si

C C C C N C N(Me)2

94

Scheme 27

(i) Solution-phase methods As shown in Scheme 28 N-benzoyl thioureas can be easily converted to N-benzoyl guanidines of type 95 by HgCl2 promoted reaction with alkyl and aryl amines <2001T1671>. N-benzoyl thioureas are also converted to the corresponding acyl guanidines using an amine in the presence of coupling reagents such as EDCI or 2-chloro-1-methylpyridinium iodide (Mukaiyama’s reagent) <2002TL57>. Bismuth nitrate pentahydrate was also found to serve as an effective reagent for guanylation of N-benzoyl thioureas (Scheme 28) <2002TL49>. O Ph

S N H

NHR2

O

i or ii or iii or iv NHR1

Ph R1, R2 = alkyl, aryl

N

NHR1

95

i. R2NH2, HgCl2, Et3N, DMF, 60–81% ii. EDCI, DAMP, Et3N, 30–74% iii. Mukaiyama's reagent, 75% iv. Bi(NO3)3.5H2O, DMF, 60–81%

Scheme 28

An improved procedure for the generation of 1-aroyl-S-methyl isothiourea derivatives 96 consists in the reaction of acid chloride (1 equiv.) in ether with S-methyl isothiouronium sulfate (2 equiv.) in sodium hydroxide under ice-cold conditions (Scheme 29). Subsequent condensation with aromatic and aliphatic amines gives the desired N-acyl guanidines 97 in 48–74% yields <2001SC2491>.

R1

Cl O

SMe + H2N

NH

NaOH 0–5 °C

H N

R1 O

SMe NH

96

R2NH2, Et3N Xylene, reflux

R1

N

NHR2 NH2

O

97

R1 = aryl, thienyl; R2 = alkyl, aryl

Scheme 29

(ii) Solid-phase methods N-acylation of the resin-bound S-methyl isothiourea 98 with carboxylic acid using 7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) as coupling reagent followed by displacement of the thiomethyl group with ammonia, a variety of

625

Functions Containing an Iminocarbonyl Group

primary or secondary amines or aniline resulted N-acyl-N0 -alkyl(aryl)guanidines 99 which are liberated from the resin upon exposure to TFA (Equation (12)) <2001TL1259>. H N

O O

O

i, ii, iii

SMe

R1

NH

NH2 NR2R3

N

ð12Þ 98

99

i. R1PyAOP, DIPEA, NMP; ii. R2R3NH, NMP; iii. TFA, DCM

In a similar manner, starting from amino acid immobilized on polystyrene Wang or Rink amide resin, the synthesis of N-acyl-N0 -carbamoyl guanidines can be achieved <1998TL9789>. The resin-bound pyrazole carboxamidine 100 upon deprotonation with lithium hexamethyldisilazide (LiHMDS) followed by treatment with an acyl chloride affords the resin-bound guanylating agent 101. The latter compound reacts with an amine to provide resin-bound disubstituted guanidine which is cleaved with TFA at room temperature (Scheme 30) <2001JOC2161>.

Wang

H N

O O

NH N

i, ii

Wang

O

H N

N O

N

100

N

N

NH O

R1

iii, iv

2 3

R R N

O

N H

R1

101 R1 = aryl, alkyl, bn; R2, R3 = alkyl, aryl; 61–88% i. LiHMDS, THF, 0–5 °C; ii. R1COCl; iii. R2R3NH, THF; iv. TFA, DCM, 2 h

Scheme 30

6.21.1.1.7

N-Cyanoiminocarbonyl derivatives

Title compounds are most often prepared from thioureas and their derivatives. These methods include (i) the reaction of an N,N0 -disubstituted thiourea with lead cyanamide, (ii) reaction of an amine with N-cyano-N0 ,S-dimethyl isothiourea, and (iii) the reaction of an amine with dimethylcyanodithioimidocarbonate followed by treatment with alkylamine. 2-Cyanoguanidines are also obtained in high yields by reacting cyanamide (H2NCN) with carbodiimides (8; R1 = aryl, R2 = alkyl) in the presence of catalytic DIPEA (Hu¨nig base). Condensation of sodium (or lithium) dicyanamide with monoalkylammonium salts yields the corresponding monosubstituted 2-cyanoguanidines (5; R1 = CN, R2,R3 = H, R4 = alkyl) (Scheme 1) <1995COFGT(6)639>. Recently, three novel methods for preparation of 1,3-substituted cyanoguanidines 104 have been developed. One involves the reaction of commercially available diphenylcyanocarbonimidate 102 with anilines and subsequent treatment of the obtained cyano-O-phenylisourea 103 with alkylamines (Scheme 31) <1997CPB2005, 2001BMCL1749>. Dimethyl cyanodithioiminocarbonate 105 reacts similarly <1994TL8085>.

Ph

O

O N

102

Ph

CN

ArNH2, rt, 14 h 73%

Ar

H N

O N

Ph

R1NH2, base

CN

103 R1 = alkyl, aryl; base = Et 3N, Py

Scheme 31

23–73%

Ar

H N

NHR1 N

104

CN

626

Functions Containing an Iminocarbonyl Group

As shown in Scheme 32, dimethyl cyanodithioiminocarbonate 105 was converted into 2-methylthio-N,N0 -dicyano-1,3-diaza-2-propenide 106 by reaction with cyanamide in the presence of K2CO3. Alternatively, the reaction of 105 with disodium cyanamide in N,N0 -dimethylacetamide gave disodium N,N0 ,N0 -tricyanoguanidine 107 <1995CM2213>. NCN MeS

SMe 105

i

ii

67

% 83

%

CN N CN N 106 MeS

–

–

Na+

2Na

+ –

i. H2NCN, THF, K2CO3, ∆, 12 h,

CN N CN N N CN 107

ii. 2Na2NCN, DMAC, 120–140 °C, 2 h,

Scheme 32

N,N0 -diarylcyanoguanidines 109 were synthesized from N-cyano-O-phenylureas 108 and arylamines. In analogy with the reaction in which the Weinreb amide is formed, trimethylaluminum was employed to promote this displacement (Equation (13)) <1994TL8085>. N

i N H

NH2

R1

CN

ii

N

O

N H

108

R1

CN N H

ð13Þ

109

i. Diphenylcyanocarbonimidate, AcCN, reflux, 2 h ii. Aniline, trimethylaluminum, DCM, 65 °C, 2 h

The highly reactive di(imidazol-1-yl)cyanomethanimide 110 readily reacts at room temperature with both alkyl- and arylamines to yield the corresponding cyanocarboximidazoles 111. In turn, 111 is converted to cyanoguanidines of type 112 in refluxing THF (Scheme 33) <2002JOC7553>.

NCN N

N

N

NCN

R1R2NH N

THF, rt

R1R2N

110

N 111

NCN

R3R4NH N

THF, reflux

R1R2N

NR3R4 112

Scheme 33

6.21.1.1.8

N-Haloiminocarbonyl derivatives

Many of the N-haloguanidines are unstable and/or explosive; therefore, most halogenations of guanidines are carried out on laboratory scale. These compounds are usually prepared by direct elemental halogenation of appropriately substituted guanidines. For example, perfluoroguanidine can be obtained by reaction of guanidine with elemental fluorine. 2-Chloro-1,1-dialkyl guanidines are prepared by oxidation with sodium hypochlorite.

627

Functions Containing an Iminocarbonyl Group

An interesting example, where 2-haloguanidine was prepared by a method other than the direct nitrogen–halogen formation is the reaction of pentafluoroguanidine with alkyl- or arylamines at low temperatures. The initially formed adduct upon warming loses difluoroamine to give a trifluoroguanidine. No further advances have occurred in this area since the publication of chapter 6.21.1.1.8 in <1995COFGT(6)639>.

6.21.1.1.9

N-Chalcogenoiminocarbonyl derivatives

(i) Oxygen derivatives The reaction of hydroxylamines with S-alkyl isothioureas and chlorformamidines 2, cyanamides 7, and carbodiimides 8 all give rise to the formation of the hydroxyguanidines (Scheme 1). N-Alkoxyguanidines are prepared analogously starting from O-alkylhydroxylamines in place of hydroxylamines. They are also synthesized by alkylation of hydroxyguanidines with alkyl halides. However, acylation of hydroxyguanidines gives the corresponding acetoxy- or benzoyloxyguanidines <1995COFGT(6)639>. Recently, guanylations of thioureas with O-benzylhydroxylamine have been described. Construction of benzyloxyguanidine group 113 can be achieved either following the activation of the thiocarbonyl group by mercury(II) oxide and subsequent displacement with O-benzylhydroxylamine <1994JCS(P1)769> or using HgCl2 as coupling reagent <2000JOC2399>. Hydrogenation of the benzyl group using 20% Pd(OH)2 as the catalyst at 0 C yields the hydroxyguanidine derivative 114 (Scheme 34).

S R1HN

i, ii (or iii) NHR2

N R1HN

R1, R2 = alkyl

OBn

iv

NHR2

N R1HN

113

OH NHR2

114

i. BnONH2 .HCl; ii. HgO, Et 3N, Et2O, rt iii. HgCl2, TEA, DMF, rt; iv. Pd(OH)2/C, H2, MeOH, 0 °C, 10 min

Scheme 34

A new convenient reagent for N-hydroxyguanylation has also been described. According to Scheme 35, 1-benzyloxycarbonylthiourea 115 was synthesized from benzyl chloroformate in two steps. Reactions of this protected urea with various amines using HgCl2 in the presence of Et3N furnished hydroxyguanidines 116 in 37–67% yields <1997SC315>.

CbzCl

KSCN

CbzNCS

S

H2NOBn CbzHN

NHOBn 115

NR1R2

R1R2HN, HgCl2 Et3N, DMF

CbzHN

NHOBn 116

Scheme 35

(ii) Sulfur derivatives The most convenient route to sulfonyl guanidines consists in the condensation of an arylsulfonyl chloride with guanidine or the reaction of arylsulfonamides with S-alkyl isothioureas. N-(alkylaminosulfonyl)guanidines can be prepared by reacting N,N-dialkyl-N0 -chlorosulfonylchloroformamidines with primary or secondary amines. The reaction of S,S-dimethyl-N-arylsulfonyliminodithiocarbonimidate or N-Ts-carbonimidic dichloride with amines leads to the formation of N-sulfonyl guanidines.

628

Functions Containing an Iminocarbonyl Group

Another method for the synthesis of sulfonyl guanidines involves the reaction of N-sulfonylN0 -alkyl carbodiimides with alkylamines. Cycloaddition reactions of sulfonyl isothiocyanates and guanidines, sulfonyl isothiocyanates and thiourea or N-sulfinyl-sulfonamides and thioureas give rise to the desired sulfonylguanidines <1995COFGT(6)639>. In recent years, a new reagent (117; Equation (14)) capable of guanylating primary amines effectively has been developed <2001OL2341>. The reaction of pyrazole 117 with aliphatic amines at room temperature affords N-Ts-protected guanidines 118 in quantitative yields, while aniline and t-butylamine are less reactive. No reaction takes place with p-nitroaniline and piperidine. N t-BOCN

N

TsCl, NaH, THF

NH2

N t-BOCHN

N

NHR1

RNH2, THF, rt t-BOCHN

NTs 117

NTs

ð14Þ

118

A series of N-aryl-N0 ,N0 -dimethyl-N0 -trifluoromethylsulfonyl guanidines 120 were prepared by reacting dimethyl cyanamide with triflic anhydride (Tf2O) followed by treatment of intermediary formed 2,3-bis-(trifluoromethylsulfonyl)-1,1-dimethylisourea 119 with aromatic amines (Scheme 36) <1995SL161>. Me

Me

Tf2O N C N

Me

OTf

DCM, 20 °C

Me

NHR1

Me

ArNH2

N

N NTf

30–58%

Me

119

NTf 120

R1 = Ph, 2-pyrimidinyl

Scheme 36

HgCl2 or EDCI were applied as coupling reagents to the syntheses of sulfonyl- and sulfamoylguanidines of type 121 from thiourea precursors (Scheme 37, methods A and B, respectively) <2000TL8075>. Similar results were obtained using HgO <1996SC4299>. S

i. NaH NH2SO2R1

R1HN

ii. R1NCS

NR2R3 SO2R1 R1HN N

iii (or iv) SO2R1

N Na

70–90%

3

4

121 R1

2

i

= Me, Ph, NH2; R = aryl, alkyl; R = alkyl; phenyl; R = H, Pr

iii. HgCl2, Et3N; (method A) iv. 1-Ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDCI); (method B)

Scheme 37

Synthesis of N,N0 -substituted guanidines 123 was also developed via an aromatic sulfonylactivated thiourea intermediate 122 <2003JOC1611>. A primary amine was first turned into a pentafluoromethyl thiocarbonate. This allowed for the synthesis of the arylsulfonyl-activated thiourea 122 using PbfNHK as nucleophile (Scheme 38). Treatment of 122 with an amine in the presence of Mukaiyama’s reagent produced subsequent guanidine 123 in very good yield. The reaction works for either primary or secondary amine nucleophiles, including the sterically hindered t-butylamine as well as diisopropylamine, both of which are known to cause problems in other guanidine syntheses performed in solution. The above was also adopted to solid-phase synthesis of functionalized amino acids. An amino acid attached to Rink amide MBHA resin was turned into the desired guanidine derivative through direct guanylation with Pbf-activated thiourea <2003JOC1611>.

629

Functions Containing an Iminocarbonyl Group S i, ii

NH2

R1

N H

R1

N H

Pbf

NR1R2 Pbf N N H

iii R1

122

123

i. Pentafluorophenylchloroformate, DIPEA, DCM

O Pbf =

ii. PbfNH2, ButOK, DMSO SO2

iii. R1R2NH, Mukaiyama's reagent, DIPEA, THF, DMF

Scheme 38

N-Sulfonyl guanidines 124 were obtained from the reaction of alkyl isocyanides with aromatic amines in the presence of chloramine T (Equation (15)). The synthesis affords N-tosyl guanidines by an experimentally simple one-pot procedure but, surprisingly, by employing alkylamines, instead of anilines, the reaction did not occur <1995TL2325>.

N

TEBA, DCM RNC:

+

ArNH2

+

TsNNaCl

R1HN

rt, 20 °C

Ts NHAr

ð15Þ

124

N-Arylsulfonyl-N0 -(pyrimidin-2-yl)-guanidines were prepared by reacting the corresponding N-acylsulfonyl guanidines with pyrimidin-2-yl-trimethylaminium chloride at room temperature for 48 h <2001KGS349>. As depicted in Scheme 39, 2-mercaptobenzenosulfonylguanidines and corresponding aminoguanidines of type 125 were obtained by selective aminolysis or hydrazinolysis of the 3-alkylamino-1,4,2-benzodithiazine derivatives <2002EJM285, 1992MI93>.

Cl

S

Me

S O

NHR1

i

N

Cl

SH

Me

S O

O

N

NHR2

O NHR1

125 R1 = alkyl, allyl; R2 = alkyl, NH2 i. H2NNH2 or R2NH2, MeOH, 20 °C

Scheme 39

Upon treatment of N-carbamoylmethyl-N0 -tosylguanidines 126 with primary amines, an unprecedented intramolecular transamination reaction was observed <2003OL3851>. The reaction leading to N-tosylguanidines 128 probably proceeds via 2-imino-4-oxoimidazolidine 127 (Scheme 40). The first synthesis of 4-substituted benzenesulfonyl cyanoguanidines 129 (Equation (16)) was accomplished by treatment of sodium salt of benzenesulfonamide with N0 -substituted-N-cyano-S-methylcarbamidothioates which were obtained by stirring a mixture of N-cyano-S,S0 -dimethylimino carbonate with the desired amine or hydrazine <1996TL7253>.

630

Functions Containing an Iminocarbonyl Group H2N

NTs

R1NH2

HN

HN

–NH3 H2N

H2 N

Ts N

HN

O

HN

NTs

R1HN

O 126

127

O

128

R1 = Me, Et, Pr

Scheme 40 SO2NH2 N R1HN

CN

N

i

+

17–82%

SCH3

R1HN

CN O2 S N H

R2

R2

ð16Þ

129 R1, R2 = alkyl

i. EtOH, NaOH, DMF, reflux

6.21.1.1.10

N-Aminoiminocarbonyl derivatives

(i) Alkyl and aryl derivatives In general, N-aminoiminocarbonyl derivatives (N-aminoguanidines) can be prepared following the procedures described previously for guanidines, i.e., from the reaction of either hydrazines with amidinium salts, thioureas, cyanamides, carbodiimides and S-alkyl thioureas, or amines with S-alkylisothiosemicarbazide and N-aminocarbonimidic dichlorides. No major improvements have been achieved in this area since the publication of chapter 6.21.1.1.10 in <1995COFGT(6)639>.

(ii) Imino, nitro, nitroso, and azido derivatives A wide range of imino and nitro derivatives of guanidines can be obtained using the well-known Bamberger reaction, which consists in the reaction of aryldiazonium salts with nitroalkyl derivatives. The use of malonic acid instead of nitroalkyl derivative gives 1,5-diaryl-3-arylazoformazanes via a 1,5-diarylformazan intermediate. Although most of the 2-nitrosoguanidines are unstable and decompose to corresponding ureas and nitrogen, the 1,1,3,3-tetraphenyl-2-nitrosoguanidine was obtained by nitrosylation of tetraphenyl guanidine and proved to be a stable solid at 20 C. Alternatively, 3-nitrosoformazans could be obtained by the reduction of 1,5-diaryl-3-nitroformazans with H2S <1995COFGT(6)639>. In recent years, several new methods for the preparation of nitroguanidines have been elaborated. Thus, 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine (DMNPC; 130) has been prepared by treatment of 1-amino-2-nitroguanidine with pentane-2,4-dione and then applied for introducing N-nitroguanidino functions as precursors of guanidino functions <1999JCS(P1)349, 1964BBA533>. The reactions of DMNPC with amines were initially carried out in 1,4-dioxane <1964BBA533>. However, it has been found that better results could be obtained when the reaction is carried out in more polar solvents such as methanol <1999JCS(P1)349>. The usefulness of DMNPC is exemplified by a facile synthesis of agmatine sulfate 131, as shown in Scheme 41. N4-Substituted N1,N8-disubstituted spermidines were obtained analogously. A similar nitroamidination with O-methyl-N-nitroisourea was applied to the synthesis of blastidic acid, a component of amino acid in an antibiotic, blasticidin S <2001TL1753>.

631

Functions Containing an Iminocarbonyl Group H N

i

NH2.HCl

CbzHN

CbzHN

ii

NNO2

SO42–

NH2 CH3 H3 C

N

H2N

+ NH2

H N

+ H3N

NH2

131 Agmatine sulfate

N NNO2

i. DMNPC, Na2CO3, MeOH, 25 °C, 3 days ii. HCO2H - MeOH, 10% Pd/C, 25 °C, 2 h

130 (DMNPC)

Scheme 41

2-Nitro-1-phenylaminoguanidine 133, 2-nitro-1-ureidoguanidine 134, and 1-(2-nitroguanidino)3-phenylurea 135 were obtained from the reaction of 1-methyl-2-nitro-1-nitrosoguanidine 132 with phenyl hydrazine, semicarbazide, and phenyl carbazide, respectively (Scheme 42). The above compounds were further oxidized with bromine to give the corresponding azo-derivatives 136 <2000ZOR1615>.

Me N NO

H2N N

R' NHNH2

NHR' NH

H2N

H2O, 20 °C

N

NO2

132

Br2, H2O

NR' N

H2N

0–5 °C

N

NO2

133 –135

NO2

136

133 R' = Ph 134 R' = CONH2 135 R' = CONHPh

Scheme 42

The synthesis of 15N-labeled nitroguanidine 137 was accomplished by treatment of guanidine sulfate with K15NO3 in concentrated sulfuric acid, as shown in Equation (17). Compound 137 was then reduced to 15N-labeled aminoguanidine 138 with zinc powder in acetic acid <2001SC2351>. NH H2N

.H SO 2 4

NH2

15

K15NO3

N

H2SO4

H2N

NO2 NH2

15

Zn

N H2N

NH2

ð17Þ

NH2

2

137

138

Moderately stable N-pentafluorosulfanyl(perfluoroalkylamino)azidomethine 140 is obtained from the reaction of NaN3 with imine 139 which, in turn, has been obtained by photolysis of SF5 with N,N-bis-(trifluoromethyl)cyanamide (Scheme 43) <1993IC287>.

(CF3)2NCN

+

SF5Cl

hν

Cl

(CF3)2N

N3

+

NaN3

(CF3)2N N SF5

N SF5 139

Scheme 43

140

632 6.21.1.1.11

Functions Containing an Iminocarbonyl Group NP, NAs, NSb, and NBi iminocarbonyl derivatives

(i) Phosphorus(III) derivatives Iminophosphoguanidines 141 (ArN¼PN¼C(NMe2)2) were obtained by the reaction of iminochlorophosphines with silylated guanidine. Examples of this class of compounds include tris(trichlorophosphoranediylamino)carbenium salts 142 (Figure 3) prepared by the photolysis of triazidocarbenium hexachloroantimonate in PCl3 <1995COFGT(6)639>.

N P

N PCl3

NMe2

Cl3P N

N

N PCl3

NMe2 141

Me2N

142

EtO

O

X P

P

Me2N

SbCl6–

EtO

N

R2N

N

R2N

NR2

156

NR2

157

Figure 3

The chemistry of guanidinylphosphines has recently been developed by Munchenberger and co-workers. Thus, dichloro-N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidinylphosphine 143 can be obtained by reacting N-trimethylsilyl-N0 ,N0 ,N0 ,N0 -tetramethylguanidine (TMSTMG) with PCl3 (Scheme 44). The analogous difluorophosphine 144 is prepared from either the reaction of fluorochlorophosphine with tetramethyl guanidine (HTMG) <1997PS57> or by treatment of triphenylmethylphosphonous difluoride with HTMG. The latter reaction involves unusual cleavage of PC rather than the PF bond (Scheme 44) <1998EJI865>. On the other hand, dichloro-bis-(pyrrolidinomethyleneimino)-phosphine 145 and dichloro-bis-(piperidinomethyleneimino)-phosphine 146 are formed upon treatment of lithiated guanidines with PCl3 (Scheme 44) <1997PS57>. From the reaction of HTMG or TMSTMG with dichlorophosphines or chlorophosphines, the corresponding alkyl(aryl)-bis-[N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidinyl]phosphines 147 and dialkyl(aryl)-[N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidinyl]phosphines 148 were obtained (Scheme 45) <1994PS103>. The compounds 147 were subsequently quaternized at the phosphorus atom upon treatment with MeI at 0 C. The substituted guanidinylphosphines 147 and 148 react with Lewis acids, boron trifluoride, and antimony pentachloride to give the phosphonium compounds of type 149 and 150, respectively (Scheme 46) <1997PS171>. Triphenylmethylphosphonous dichloride was found to react with HTMG to give chloro triphenylmethylphosphonous N0 ,N0 ,N0 ,N0 -tetramethyl guanidine 151. Triphenylmethylphosphonous N0 ,N0 ,N0 ,N0 -tetramethyl guanidine 152 was further obtained from the reaction of 151 with LiAlH4 followed by treatment with HCl (Scheme 47) <1998EJI865>. Diphosphine monoxide 154 is formed when the multifunctional 1,2-bis(tritylated)diphosphine monoxide 153 reacts with HTMG, whereas its tautomer 155 can be obtained from the reaction of chlorophosphine 151 with triphenyl methylphosphinic acid fluoride (Ph3C-PH(O)F) as shown in Scheme 48 <1999ZAAC497>.

633

Functions Containing an Iminocarbonyl Group i

Cl

72%

Cl

PCl3

P N C(NMe2)2 143

i. TMSTMG, n -hexane, 0 °C to reflux, 2 h

F

F

i P Cl 81%

F

F

ii P N C(NMe2)2

P PPh3 F

F 144

i. 2HTMG, Et2O, –80 °C to rt, 2 h ii. HTMG, CHCl3, 25 °C, 1 h

–

(CH2)n

(CH2)n i

N Li+

PCl3

N

Cl P

N Cl

22%

N

N (CH2)n

(CH2)n

145, n = 0; 146, n = 1 i. Et2O, 0 °C to rt, 2 h

Scheme 44

i R1PCl2

R1P

71 – 75%

N C(NMe2)2

ii

Me

N C(NMe2)2

+

I–

P R1

N C(NMe2)2

N C(NMe2)2

R1 = Me, But, Ph

147

i. 4HTMG, petroleum ether, 0 °C to reflux, 4 h, ii. MeI, Et2O, 0 °C

R1

i

P Cl R2

R1 P N C(NMe2)2

R2

148

A

R1

R2

Yield (%)

Pri

Pri

74

Ph

78

Ph

61

B

Bu

C

Ph

t

i. TMSTMG, petroleum ether, 0 °C to reflux, 3 h

Scheme 45

(ii) Phosphorus(V) derivatives Two major classes of phosphorus(V) derivatives described in <1995COFGT(6)639> comprised (i) guanidinylphosphoric diamides 156 obtained from the reaction of phosphoryl chlorides with guanidines, and (ii) bis-(dialkylamino)methylenephosphoramidic esters 157 generated by the reaction of dichloromethylenephosphoramidic compounds with dialkylamines (Figure 3).

634

Functions Containing an Iminocarbonyl Group

Ph

2BF3.Et2O

Ph

Et2O, –50 °C, 2 h

Ph

–

+ P N C(NMe2)2 Ph

F3B

Ph P P Ph

N C(NMe2)2 F3B

N C(NMe2)2

149

+

R1

i P N C(NMe2)2

R1

Ph

–

Ph P Cl

SbCl6

N C(NMe2)2 R1 = Ph; 55% R2 = TMG; 60%

150 i. 2SbCl5, Et2O, –80 °C, –SbCl3

Scheme 46

Cl Tr

P Cl

Cl

i

Tr

84%

H

ii, iii, iv

P

Tr

N C(NMe2)2

Tr = Ph3C–

.2HCl

P N C(NMe2)2

152

151 i. TMSTMG, toluene, rt, 3 h; ii. LiAlH4, Et2O, 0 °C to rt, 1 h iii. H2O, rt; iv. toluene, 1 M HCl/Et2O, rt, 71%

Scheme 47

O PhC P H F

O P P FP Tr Tr

i

Cl

Ph3C–PCl2 Et3N, DCM, rt, 2 h

+

HTMG

(Me2N)2C N

O P P F Tr Tr

153

Cl Tr

154

+

P

Tr

N C(NMe2)2

H P O F

ii

151

Tr (Me2N)2C N

P F P O

Tr 155

i. CDCl3, rt, 1 h; ii. Et 3N, DCM, rt, 5 h

Scheme 48

Functions Containing an Iminocarbonyl Group

635

Recently, phosphorus pentachloride has been found to react with 2 equiv. of TMSTMG to give bis-N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidinyltrichlorophosphorane 158 (Equation (18)) <1997PS57>. i

+

PCl5

2TMSTMG

Cl –2MeSiCl 67%

Cl N C(NMe2)2 P N C(NMe2)2 Cl

ð18Þ 158

i. Et2O, 0 °C, 2 h

The phosphorus compounds 147 react readily with sulfur, selenium, and tellurium to give the corresponding chalogenide derivatives 159 (Scheme 49) <1994PS103>.

R1P

X, i or ii

N C(NMe2)2 N C(NMe2)2

N C(NMe2)2 R1 P N C(NMe2)2 X

147

159 R1

X

Me

S

78

i

But

S

86

i

Ph

S

91

i

Ph

Se

79

ii

Ph

Te

71

ii

Yield (%) Conditions

i. 1/8 S, toluene, rt, 2 h; ii. Se or Te, rt, 3 days

Scheme 49

As shown in Equation (19), treatment of the chlorophosphonous guanidine 151 with Et3N in H2O gives triphenyl methylphosphonous N0 ,N0 ,N0 ,N0 -tetramethyl guanidine 160 <1998EJI865>. Cl Tr

P

Et3N, H2O Tr

N C(NMe2)2 151

O P H N C(NMe2)2

ð19Þ

160

A series of guanidine-containing phosphorylamides 161–166 have been prepared in the reaction of the appropriate chlorophosphoryl compounds with either HTMG or TMSTMG (Scheme 50). In contradistinction to guanidinylphosphine 147, the phosphoryl amide 161 undergoes N-alkylation with methyl iodode to give the ammonium salt 167 <1996ZAAC348>. fluorides 168 The organophosphorus N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidine (RP(F)N¼C(NMe2)2; R = t-Bu, Ph) were synthesized and oxidized by sulfur, selenium, and tellurium as well as by the urea-H2O2 1:1 adduct to give the phosphonic acid derivatives 169–172. Compound 168 (R = Ph) undergoes a Staudinger reaction with triphenylmethyl azide to produce the phosphine imide 173 (Scheme 51) <1996ZN1150>. A convenient synthesis of thiophosphinyl guanidines 174 has also been described <1995SC2857>. The reaction sequence involves initial preparation of sodium thiophosphinyl cyanamide Na[Ph2P(S)NCN] which then reacts with alkyl- and arylammonium chlorides [RNH3]Cl to give the corresponding alkyl- and arylammonium thiophosphinyl cyanamides. The latter compounds, when heated at 130–190 C, rearrange to N-alkyl(aryl)-N0 -thiophosphinyl guanidines 174 in a Wo¨hler-type reaction (Scheme 52).

636

Functions Containing an Iminocarbonyl Group O

163

R1

P

O

N C(NMe2)2 R2

R1

R1 = Me; R2 = Et2N R1

= Ph;

R2

R1

O P

= Ph

Cl

O P

R2

Cl

Cl

Cl 2 equiv.

Cl

R1

O

Cl P

N C(NMe2)2

P Cl

O

Cl

Cl

HTMG

Cl

162

Cl

P

2 equiv.

O

N C(NMe2)2

R1 = Ph, Tr

R1

O

P

1

P

161

N C(NMe2)2

R

4 equiv.

N C(NMe2)2

R1 = Me, But, Ph

164 O O

Cl P

Cl

i. TMS

P

Cl

O

ii.

Cl

O O

N C(NMe2)2

O

P

P

P Cl

N C(NMe2)2

(Me2N)2C N 165

MeI

P But

(Me2N)2C N

R1 = Me

Cl Cl

O

N C(NMe2)2

P Me

But

N C(NMe2)2 N C(NMe2)2 Me

166

167

Scheme 50

NTr 1

R

P

F

173

N C(NMe2)2

i. Toluene, rt, 2 h

TrN3, i %

87

F R1

P N C(NMe2)2 168

O

H2O2 /urea, i

R1

63–75%

P

i. 0 °C to rt, 2 h

X, i

X 1

R

P

F N C(NMe2)2

169 , X = S; i. toluene, rt, 2–16 h, 73–87% 170 , X = Se; i. toluene, rt to 60 °C, 61–67% 171 , X = Te; i. toluene, rt, 3–16 h, 44–52%

Scheme 51

F 172 N C(NMe2)2

I

–

637

Functions Containing an Iminocarbonyl Group S Ph2P

–

+

Na2NCN

Na

R1NH3+ Cl-–

S

+

R1NH3

Ph2P

Cl

NCN

130–190 °C

S

+

–

Ph2P NCN

S Ph2P

NH2 N C NHR1 174

R1 = Bun, But, c -hexane, Ph, p-ClC6H4

Scheme 52

Phosphoryl thiourea 175 can be converted into N1,N1-diphenyl-N3-dialkoxyphosphoryl guanidine 177 in three steps (Scheme 53). First, the compound 175 is reacted with allyl bromide to give S-alkenylated product, which upon vacuum distillation in the presence of catalytic amount of hydroquinone undergoes -elimination of allyl mercaptan giving rise to the formation of N-phenyl-N1-dialkoxyphosphoryl carbodiimide 176 in 50% yield. The final product 177 is obtained by reacting 176 with aniline at room temperature <1994ZOB931>.

O (PriO)2P

Br, Et3N

S N H

O (PriO)2P

NHPh

∆, 0.05 mmHg

S N

NHPh

-

SH

175 NH2

O (PriO)2P

N

C

NPh

O (PriO)2P

rt

176

NHPh N

NHPh

177

Scheme 53

(iii) As, Sb, and Bi derivatives The only report mentioned in <1995COFGT(6)639> referred to dative-bonded complexes of guanidines and bismuth or antimony trihalides. In 1994 a reaction of TMSTMG with MeAsCl2 leading to methyl [N-(N0 ,N0 ,N0 ,N0 -tetramethyl)guanidinyl]chloroarsine 178 was described (Equation (20)) <1994PS103>. TMSTMG, rt, 2 h MeAsCl2 –Me3SiCl

Me As N C(NMe2)2 Cl

ð20Þ

178

An interesting complex between antimony(III) and guanidine is also described <1997CC1161>. 1,2,3-Triisopropyl guanidine reacts with antimony tris(dimethylamide) (Sb(NMe2)3) to give complex 179 in which the Sb is chelated by a [C(NPri)3]2 dianion and a [iPrN)2CNHPri] monoanion (Equation (21)).

638

Functions Containing an Iminocarbonyl Group

PriHN

Sb(NMe2)3

C NPri PriHN

Pri Pri 2– N 3 + N– PriN Sb NHPri N N Pri Pri

ð21Þ

179

6.21.1.1.12

NSi, NGe, and NB iminocarbonyl derivatives

According to chapter 6.21.1.1.12 in <1995COFGT(6)639>, N-silylated guanidines 180 (Figure 4) and guanidinium salts [Me2N)2CHTMS]+ Hal were prepared by reacting the corresponding guanidine with a chlorosilane in the presence of a base and in the absence of added base, respectively. H+ N Ar3B–

NMe2 N TMS

NMe2

180

NHR NHR

181

Figure 4

N-Borated guanidines were represented by triarylboron complexes 181 (Figure 4) and no N-germylated guanidine derivatives were described in <1995COFGT(6)639>. Recently, N-silyl-N0 ,N0 ,N0 ,N0 -tetramethyl guanidine (TMSTMG) was applied to the synthesis of 2-azonioallene salts of type 182 (Equation (22)) <1989S400>. Cl

SbCl6–

Me2N + NMe2

i

NSiMe3

+ Me2N

NMe2

NMe2

Me2N N

–Me3SiCl 78%

Me2N

NMe2

SbCl6–

ð22Þ

182 i. 1,2-dichloroethene, –50 °C to –20 °C

23 °C, 5 h

A new class of SiN bonded compounds 183 was obtained from the reaction of biguanide and its N-alkyl derivatives with diorganosilanes R1R2SiNH2 (R1,R2 = Ph; R1 = Me, R2 = Ph) <2001JCS(D)1582>. The reaction proceeds via SiH/NH dehydrocoupling and affords corresponding oligomeric 1,4-bis-(silyl)biguanides (Equation (23)).

H2N

N NH

NHR3 NH2

R1R2SiNH2 THF, reflux, 16 h

H

R1 H Si N R2

N

R3 N

NH NH H Si R1 R2

R3 = H, Pr, cyclohexyl

H

ð23Þ n

183

Guanidinate anions of type 184 are generated by the reaction of lithium bis(trimethylsilyl)amide (LiN(SiMe3)2) with 1,3-alkyl carbodiimides (R1,R2 = iPr, cyclohexyl) (Scheme 54). Lithium salts 184 were isolated in pure form and used for preparation of a series of bis- and monoguanidinate complexes of Zr and Hf <1999IC5788>, Nb and Ta <1999POL2885>, as well as Yb and Sm <1998OM4387>. As depicted in Equation (24), the [2+2] cycloadditions that take place between imidozircocene complexes and 1,3-di-(trimethylsilyl)carbodiimide give other types of diazametallacycle complexes 185 <2001OM1792>.

639

Functions Containing an Iminocarbonyl Group

(Me3Si)2N– Li+

+

Me3Si

R1N=C=NR2

R1

Et2O, rt, 4 h

N

N

SiMe3 N

R

Me3Si

M(X)n

2

R1

N

N

Li

SiMe3 N

R2

M(X)n

184

Scheme 54

Cp2Zr

But N

NBut

Me3SiN C NSiMe3

Zr

C NSiMe3 N SiMe3

ð24Þ

185

6.21.1.2

Iminocarbonyl Derivatives with One Nitrogen and One P, As, Sb, or Bi Function

6.21.1.2.1

N-Alkylimino derivatives with one P or As function

Title compounds 186 (Figure 5) were usually obtained by Michaelis–Arbuzov reaction of the carbamimidic chlorides with trimethyl phosphite (P(OMe)3). Another method for preparation of 187 consists in the attack of alkali metal organoarsenides at N,N0 -dialkyl carbodiimides followed by hydrolysis or alkylation of the intermediary formed (lithioamidino)arsines <1995COFGT(6)639>.

Bun NR'R3

CO2Et RN

O P MeO OMe

R'N

NR2R3 ArN P(OR1)2

AsR22

186

O

187

189

CF3 N Ph P(OEt)2

PhN

PhN PR1R2

O 190

O

N(Ph)R3

191

RO

NEt N

P(OR)2 O

195

Figure 5

Recently, the phospha(III)guanidine compounds of the general formula Ph2PC(NR) (NHR);R = Pri, cyclohexyl) have been prepared in good yields as described in Scheme 55. Lithium diphenylphosphide obtained by treatment of Ph2PH with BuLi is allowed to react with suitable carbodiimide giving the corresponding lithium phospha(III)guanidinate. Quenching the reaction with triethylamine hydrochloride yields the neutral phospha(III)guanidines 188 <2002CC2794, 2003JCS(D)2573>.

640

Functions Containing an Iminocarbonyl Group Ph P Ph

R1 N i, ii

R1

Ph2PH Ph

N

P Ph

Li Li

N

NR1

iii 71%

R1

N R1

Ph2P

R1 = Pri, cyclohexyl

NHR1 188

i. BuLi in hexanes, THF, 0 °C, 0.5 h ii. Carbodiimide, THF, 0 °C to rt, overnight iii. Dry [HNEt3][Cl], THF, rt, 1 h

Scheme 55

6.21.1.2.2

N-Arylimino derivatives with one P function

There are three methods described in <1999COFGT(6)639> for the preparation of amidinophosphonates of type 189 (Figure 5). The first involves the reversible reaction of N,N0 -diphenyl carbodiimide with a phosphite triester. The second method consists in the direct aminolysis of iminochlorides of general formula ArN = C(Cl)P(O) (OR1)2. The third method is based on a Michaelis–Arbuzov reaction of the amidinochlorides with trialkyl phosphites. When a chloroalkylcarbodiimide was used instead of carbodiimide in a variant of a Michaelis–Arbuzov reaction, the corresponding alkylideneamidophosphonate 190 could be obtained. Amidinophosphines 191 (Figure 5) are usually prepared by the addition of phosphines containing PH or PSi bond across the C¼N bond of carbodiimide. Thus, the reaction of monophenylphosphine (PhPH2) with carbodiimide gives the bis(amidino)phosphine and analogous reaction of carbodiimide with diphenylphosphine (Ph2PH) leads to the formation of mono(amidino)phosphine <1995COFGT(6)639>. In 1995 Komalov and co-workers described a facile synthesis of novel dialkyl-Narylimino(amidino)phosphonates 192 <1995ZOB46>. The addition of anilidophosphines to carbodiimides carried out at room temperature afforded the compounds 192 in 87–97% yield (Equation (25)). NR2 NHR3 R1O P 3 OR1 NR

R1O P NHR2

R3N=C=NR3

+

R1O

ð25Þ

192 1

i

2

3

R = Et, Pr ; R = Ph, Tol; R = Ph, cyclohexyl

The C-phosphorylated N,N-dimethyl-N0 -tolyl formamidines 194 are obtained starting from N,N-dimethyl-N0 -tolyl formamidines, which reacts with PBr3 to give the dibromophosphine 193. The above reaction represents the first example of electrophilic substitution at a formamidine carbon atom. Then, the intermediate 193 upon treatment with dialkylamine and elemental sulfur is converted into the desired C-phosphorylated amidines 194 in 40–44% yields (Scheme 56) <1996ZOB1930>.

6.21.1.2.3

N-Acylimino derivatives with one P function

N-Acylimino derivatives are usually generated from dichloromethyl isocyanate precursors bearing the dichlorophosphine moiety. First, in the reaction with alcohols they are converted to chloroimines, which, on treatment with diethylamine, give the N-acyliminoamidinophosphonates 195 (Figure 5). No major progress has been made since the publication of <1995COFGT(6)639>.

641

Functions Containing an Iminocarbonyl Group

Me

Me N Me

N

+

Br2P

Pyr PBr3

Me

Et3N, 0 °C

N

Me N Me

193 S (R1R2N)2P

i. R1R2NH 1

ii. /8 S, rt, 8 h

Me

N

Me N Me

R1, R2 = Me, Et

194

Scheme 56

6.21.1.2.4

N-Haloiminocarbonyl derivatives with one P function

Phosphorylnitrile oxide generated in situ from the corresponding hydroxamic acid chloride is easily converted into phosphorylamidoxime 196 upon treatment with aliphatic and aromatic amines, benzhydrazide, or semicarbazide (Scheme 57). The reactions are carried out at room temperature or at reflux for 5 min in solvents such as chloroform and acetonitrile. In the case of semicarbazide the hydroxamic acid chloride is treated with KOH in PriOH <1995ZOB1991>. O (PriO)2P

NOH

O (PriO)2P

R1NH2 C

Cl

N O

O (PriO)2P

NOH NHR1

196 R1 = Bu, Ph, 4-NH2C6H4, 4-O2NC6H4, NHC(O)NH2, NHC(O)Ph

Scheme 57

6.21.1.2.5

Hydrazono derivatives with one P function

N0 -Aryl-C-(dialkoxyphosphoryl)formamidrazones (197; X = NMe2) (Figure 6) were obtained from the reaction of corresponding chlorohydrazono derivatives with aqueous solution of amines or phenylhydrazine. Similarly were obtained the azido and nitrohydrazones (197; X = N3, NO2). The 1,3-addition of mono- or dialkylamines to nitrile imines (Ar2PNN+CP(S) (NR1R2)2) furnished N0 -phosphineformamidrazones 198 (Figure 6). (Arylhydrazono)arylazomethyl)phosphonates 199 (Figure 6) were obtained by coupling reaction of phosphinyl acetaldehyde with diazonium salts. Alternatively, the coupling reaction of the triphenylphosphine acetic acid with 2 molar equiv. of diazonium salt furnished the bis(arylazo)methylenephosphine 200 (Figure 6). Oxidation of the dialkoxyphosphorylamidrazone with silver(I) oxide gave the N-(arylazo)dialkoxyphosphoryl)methyleneamine 201 (Figure 6). No further advances have occurred in this area since the publication of chapter 6.21.1.2.4 in <1995COFGT(6)639>.

6.21.1.2.6

Diazonium derivatives with one P function

Title diazomethane derivatives 202 (Figure 7) are usually obtained by the treatment of diazomethylphosphonates with dinitrogen pentoxide (N2O5). Since the publication of chapter 6.21.1.2.5 in <1995COFGT(6)639> no further advances have occurred in this area.

642

Functions Containing an Iminocarbonyl Group X ArHN

NPr2i

R1 P R2

N

Ar

O

Ar

197

N=NAr

ArHN NPr2i

H N N P

P

N

NPr2i

P(OR)2 O

S 198

199

X = NMe2, N3, NO2

N=NAr

N=NAr

ArHN

RN

– BF4

N

P(OR1)2

PPh3 + 200

O 201

Figure 6

NO2 R1 P R2

N2 O

202

NR22

+ R22N –

X

NR22

+ R22N

NR22

OEt

NR22

+ R22N

Ph

P

P NR22

P OEt

O

203

204

O

Ph

205

Figure 7

6.21.1.2.7

N,N-Dialkyliminium derivatives with one P function

In chapter 6.21.1.2.6 in <1995COFGT(6)639> the following methods were described for preparing the title compounds. For the syntheses of phosphaallylic salts and phosphorylated amidinium salts, N,N,N0 ,N0 -tetramethylimidoyl chloride is used as starting material: (i) it reacts with 0.5 molar equiv. of tris(TMS)phosphane (P(TMS)3) to give compounds 203 (Figure 7); (ii) upon treatment with triethyl phosphite the monophosphorylated amidinium salts 204 are obtained; and (iii) it undergoes a standard Michaelis–Arbuzov reaction with alkyl diphenylphosphinite having only one displaceable alkyl group to give the salt 205. Although the majority of phosphaalkenes show a polarity P+C of P¼C double bond, in a number of P-acyl, P-dithiocarboxyl, and P-thiocarbamoyl-phosphaalkenes, an inverse polarity PC+ of the multiple bond is observed. Recently, the synthesis, structure, bonding, and coordination chemistry of these derivatives have been investigated in detail <1998OM3593>. Replacement of the P-silyl group in P-trimethylsilyl-substituted phosphoalkanes 206 by acyl, dithiocarboxy, and thiocarbamoyl functions leads to the compounds 207, 210, and 211, respectively (Scheme 58). Based on a significant deshielding of the 31P NMR resonances and X-ray structure analysis, the electronic configuration was described by canonical formulas 207, 208, and 209 (Scheme 58). X-ray structure analysis of 210 confirmed the existence of multiple bonding of planar carbenium center (C5) to the planarly configured atoms C(2)N(1) and C(2)N(3). Reactivity of the carbonyl-functionalized phosphaalkanes 207 toward protic acids, Lewis acids, and alkylating and silylating agents were investigated by Weber and co-workers <1999EJI2369>. It was found that the reaction with protic acids and alkylating agents occurred at two-coordinate phosphorus atom yielding the phosphanyl-substituted amidinium cations 212 and 213. Silylation with Me3SiOSO2CF3 resulted in the attack at the oxygen atom (formation of 214). Also Lewis acid B(C6F5)3 was ligated at the oxygen atom of carbonyl group to give the adduct 215 (Scheme 59). The structures of the adducts of 207 with the homologous Lewis acids AlMe3, GaMe3, and InMe3 were also investigated in detail. AlMe3 was ligated to the oxygen atom of the carbonyl

643

Functions Containing an Iminocarbonyl Group O R1

NMe2

O

P

P R1

NMe2

207

–

–

O

NMe2 + NMe2

P R1

208 R1

NMe2 + NMe2

209

COCl S

CS2

NMe2

Me3SiS

NMe2

Me3SiP

P NMe2

206

NMe2

210

PhNCS

Me3Si

S N

Ph

NMe2 P NMe2

211

Scheme 58 O R1

Me NMe2 + P NMe2

–

SO3CF3

213

CH3OSO2CF3 R1 O

NMe2 + NMe2

P H BF

HBF4/Et2O

O

NMe2 P

R1

NMe2

Me3SiSO2CF3

SiMe3 O NMe2 – + P SO3CF3 NMe2 R1

–

212

207

(C6F5)3B O

214

NMe2 + NMe2

P R1 215

Scheme 59

group; 2 molar equiv. of GaMe3 were added to the oxygen and phosphorus atom, and InMe3 was bound to the phosphorus center of the phosphaalkane (Scheme 60) <1999EJI2369>. Molecules of type 210 and 211 were found to behave as multidentate ligands in transition metal chemistry (Equation (26)). Thus, they reacted with (CO)5MBr (M = Mn, Re) to afford tricyclic complexes 216 and 217 <1998OM3593>. Complexation of 207 with transition metal carbonyls took place at the pnictogen atom resulting in the complexes of type 218 (RC(O)P[M(CO)n]C(NMe2)2) (R = t-Bu, Ph; M = Ni, n = 3; Fe, n = 4; Cr, n = 5) (Equation (27)).

644

Functions Containing an Iminocarbonyl Group –

AlMe3 O NMe2 + P NMe2 R1 AlMe3

–

O

NMe2 P

R1

InMe3

O

InMe3

P R1

NMe2

NMe2 + NMe2

207

2GaMe3 –

Me3Ga O

GaMe3 P

R1

NMe2 + NMe2

Scheme 60 S X

(CO)5MBr

210, 211

–Me3SiBr, – 4CO

NMe2

L

L M

P P L L L M Me2N S Me2N L

NMe2

ð26Þ

X

L = CO, M = Mn, Re; 216 , X = S; 217 , X = NPh

O

NMe2

O P

P R1

R1 M(CO)4

NMe2 207

6.21.1.3 6.21.1.3.1

NMe2 + NMe2

ð27Þ

218

Iminocarbonyl Derivatives with One Nitrogen and One Metalloid Function Silicon derivatives

A compound of this class, silanecarboximidamide 219 (Figure 8), was prepared by the reaction of N,N0 -diphenyl carbodiimide and bis(TMS)mercury <1995COFGT(6)639>. Since the publication of chapter 6.21.1.3.1 in <1995COFGT(6)639> no further advances have occurred in this area.

N(Ph)TMS R1N

PhN TMS

R2 N

NMe2 2

BR

–

PhN

2

B 4

R 219

220

R1

+ N R3 R4

221

Figure 8

PhN

N

+ – N Bu B H Bu 222

645

Functions Containing an Iminocarbonyl Group 6.21.1.3.2

Boron derivatives

N-Alkylboranecarboximidamide 220 (Figure 8) is formed as a by-product of the reaction of -lithio-N,N-dimethylacetamide with bromodimethylborane. Other examples of borane carboximidamides 221 and 222 can be prepared by reacting phenyl isocyanide with boraneamide and 2-(dialkylboryl)aminopyridine, respectively <1995COFGT(6)639>. Recently, novel types of [amine-bis-(amidinium) hydroboron2+] 225 and [amine-bis(triethylamidinium)hydroboron2+] 226 cations have been obtained <1999IC5250>. First, the cyano groups of 223 are activated by ethylation employing Et3OBF4 to give [amine-bis(ethylnitrilium)hydroboron2+] tetrafluoroborates 224. Then, nucleophilic addition of ammonia and diethylamine gives 225 and 226, respectively (Scheme 61).

CN

C N Et

Et3OBF4

A HB CN

DCM, reflux, 25 h

i –

A HB

2+

H2N

2+ 2BF4

C NHEt

C N Et

–

2BF4

A HB C NHEt H2N

223

224 225 ii

2+

Et2N C NHEt

–

2PF6

A HB C NHEt Et2N

i. Liquid NH3, –30 °C, 5 min ii. Et2NH, rt, 5–10 min, then H2O, NaPF6

226

Scheme 61

6.21.1.4 6.21.1.4.1

Iminocarbonyl Derivatives with One Nitrogen and One Metal Function Main metal derivatives

The trialkylstannyl and trialkylplumbyl formamidines 227 (Figure 9) were obtained by the 1,1-addition of a metal amide to an aryl isocyanide <1995COFGT(6)639>. Adducts of InMe3 with aryl isocyanides of general structure Me3InCNR (228, R = 4-MeC6H4, 4-OMeC6H4) react slowly at room temperature with pyrrolidine to give the insertion products 229 (Scheme 62). The same compounds were obtained by reacting InMe2Pyrr 230 with corresponding isocyanides <2001JOM11>.

6.21.1.4.2

Transition metal derivatives

The nucleophilic attack of azetidine at the carbon atom of coordinated isocyanide ligands of the neutral or cationic complexes of Pd and Pt resulted in the formation of the diaminocarbene complexes 231 and 232, respectively (Figure 9). The reaction of tetrakis(t-butyl isocyanide)rhodium(I) tetrafluoroborate with dimethylamine and diethylamine gave 1:1 adducts 233 containing a -bonded amidinium cation <1995COFGT(6)639>.

646

Functions Containing an Iminocarbonyl Group NR22

NHR

ArN

N

MR13

M(PPh3)Cl2

227

231

M = Sn, Ar = 4-MeC6H4, R1 = R2 = Me M = Pb, Ar = Ph, R1 = Bu, R2 = Et

+ OMe

HN N

R2N

–

BF4

Rh(C But

M(PPh3)Cl

–

NBut)3 BF4

HN + 233

232 M = Pd, Pt

Figure 9

NR InMe3

RNC, i

+

Me3In

ii

iii Me2In N

N

Me3InCNR

228

229

230

i. n-Hexane, rt, 24 h ii. Pyrrolidine, n-hexane, rt, 33 days iii. RNC, n-hexane, rt, 2 months

Scheme 62

Pentacarbonyl {(dimethylamino)[methoxy(phenyl)methyleneamino]carbene} complexes of molybdenium(0) and tungsten(0) 234 react with chloroauric acid to give chloro {(dimethylamino)[methoxy(phenyl)methyleneamino]carbene}gold(I) 235 and trichloro {(dimethylamino)[methoxy(phenyl)methyleneamino]carbene}gold(I) 236 (Scheme 63) <1981CB3412, 1981AG(E)461>. Compounds 235 and 236 react with boron tribromide to give the tribromo derivative 237, which, in turn, is converted into triiodo gold complex 238 upon treatment with boron triiodide <1985JOM279>.

(CO)5M

NMe2 Ph N OMe 234

HAuCl4

ClAu

NMe2 Ph N OMe

Cl3Au

235

M = Mo(II), W(III)

Br3Au

NMe2 + Ph N OMe

BI3

237

236

I3Au

NMe2 Ph N OMe 238

Scheme 63

NMe2 Ph N OMe

PBr3

647

Functions Containing an Iminocarbonyl Group

Isocyanide complex [AuCl(CNBut)] 239 reacts with terminal alkynes in diethylamine to give the corresponding alkynyl(carbene) complexes 240 and 241 (Scheme 64) <1997OM5628>. NHBut RC C Au

i [AuCl(C

240 NEt2

R = H, But, SiMe3

NBut]

239

ii

ButHN

NHBut Au C C(CH2)5C C Au

Et2N

NEt2 241

i. RC CH, Et2NH, rt, 17–24 h ii. HC C(CH2)C CH, Et2NH, rt,14 h

Scheme 64

As shown in Equation (28), the insertion reaction of aryl isocyanides with zirconium amido silyl complex leading to the compound 242 has recently been described <1999OM1002>. Si(SiMe3)3 Zr NMe2 Me2N NMe2

ArNC

Me2N Me2N

Si(SiMe3)3 Zr NMe2

Ar

NMe2

N

Me2N

Zr Si(SiMe ) 3 3 NMe2

C N Ar

ð28Þ

242 Ar = 2,6-Me2C6H3

The carbodiimide complex 244 and the four-membered metallacycles 245 are obtained from the reaction of the isocyanide metal precursors (243, M = Co, Rh) with aryl azides (Scheme 65). As evidenced by NMR spectroscopy, the compound 245 exists in equilibrium with isomer 246 <1998JOM(551)367>.

6.21.2

IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P, As, Sb, OR Bi FUNCTION (AND NO HALOGEN, CHALCOGEN, OR NITROGEN FUNCTIONS)

6.21.2.1

6.21.2.1.1

Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function and One P, As, Sb, or Bi Function Bis(phosphino)iminocarbonyl derivatives

Phosphorus compounds of type 247 (Figure 10) in which the carbon atom of the iminocarbonyl group is attached to two three-valent phosphorus atoms were found to be unstable, and, therefore, little is known about their properties. The more stable (diazomethylene)-bis(phosphonous diamides) 248 were obtained by addition of the lithium salt of the bis(phosphanyl)diazomethane to the chlorophosphane <1995COFGT(6)639>. [Bis(diisopropylamino)phosphonio][chloro(isopropylamino)phosphino]diazomethane 249 is readily available by addition of the lithium salt of [bis(diisopropylamino)phosphino]diazomethane to dichloro(isopropylamino)phosphane (Equation (29)) <2000AG(E)3319>. Interestingly,

648

Functions Containing an Iminocarbonyl Group

Me3P

M

ArN3 CNR

M

Me3P

–N2

+

NAr

Me3P

C

NR

N Ar

RN

RN 243

M

244

245

M = Co, Rh; Ar = Ph, Tol; R1 = C6H11, bn

Me3P

Co

NC6H11

C N Ph

H11C6N

Co

Me3P PhN

C

NC6H11

N C6H11 246

245

Me3P

Co

+

CNC6H11

H11C6N + NPh

Scheme 65 Ph P(NR2)2

P TMS N2

ArN

P(NR2)2

P Ph TMS 247

248

Figure 10

(phosphino-(P-chlorophosphonio)diazo derivative 252, obtained by addition of bis(diisopropylamino)phosphonium salt 250 to P-chlorodiazomethylenephosphorane 251 at –30 C, appeared to be unstable with respect to dinitrogen elimination, which began at 23 C and led to the corresponding carbene 253 (Scheme 66) <1996IC46>. R

N2 P C

+

i

R

RPCl2

Li

R

N2

R

P C P Cl

R

ð29Þ 249 R = Pr2i N i. THF, –78 to 0 °C, 1 h

Cl R P C N2 R

–33 °C

+

250

+

–

R2P TfO

R

251

R P

Cl R P R C N2 252

R = Pr2iN

Scheme 66

>–23 °C R

R P

Cl + R P C R

–N2 253

649

Functions Containing an Iminocarbonyl Group

Diphosphirenium salt 254 reacts with t-butyl isocyanide at 50 C to give four-membered heterocycle 255 featuring a 32-phosphorus–carbon double bond <1994CC337>. The latter compound upon treatment with nucleophiles such as butyl- or methyllithium forms a phosphorus heterocycle 256 (Scheme 67).

NR2 +

P

+

NR2 But–NC

NR2 P NR2

–50 °C

– BF4

C N But

P

NR2 P NR2

NR2 –

BF4

254

NR2

NR2 P P+ NR2 C – BF4 N But

R1–Li

NR2

R1P

P C N

255

NR2 But

256

R = Pri; R1 = Me, Bu

Scheme 67

Alkyl and aryl isocyanides are able to cleave the P¼P bond in the metallodiphosphenes of type 257 to give either the 3-diphosphiranimine 258 or 2,4-diimino-1,3-diphosphetanes 259 (Scheme 68) <1994OM4406, 1995ZAAC1407, 1998JFC73>.

R1

P P

R2

N RNC

RNC R1 P P R2

N

R 257

258

R P R2

R1 P N

R 259

R = Ph, 2-MeC6H4

R = C6H11, bn

R1 = cp*(CO)2Fe, C(SiMe3)3

R1 = cp*(CO)2Fe

R2 = C(SiMe3)3

R2 = 2,4,6-Bu3tC6H2

Scheme 68

6.21.2.1.2

Bis(phosphinyl)iminocarbonyl derivatives

This class of compounds containing five-valent phosphorus atoms includes diphenyl-, dialkoxy-, diamino-, alkoxyamino-, and alkoxyfluoro-phosphinyl derivatives, all of which can be synthesized according to the following methods <1995COFGT(6)639>. (a) From carbonimidic dichlorides and organophosphorus reagents, such as (RO)2P(O)R and Ph2P(O)(OR), were obtained (arylcarbonimidoyl)bisphosphonic acid esters 260, bis(diphenylphosphinyl)methylene)arylamines 261, respectively (Figure 11). Analogously, the Michaelis–Arbuzov reaction of phenylsulfonylcarbonimidic dichloride with (RO)3P gives derivatives 262. (b) From carbimidic dichlorides by metal–halogen exchange with Me2TlP(O)Ph2 the compounds 261 are produced (Figure 11). (c) (Diazomethylene)bisphosphonates 263 are prepared by treatment of the corresponding CH active methylene precursor with tosyl azide in the presence of potassium t-butoxide. (d) Reaction of the lithium salt of the thioxophosphoranyldiazomethane with chlorophosphane derivatives leads to the phosphinothioyl compounds 264 (Figure 11). (e) P,P0 -(carbonimidoyl)bis(phosphonic amide) 265 is obtained from the reaction of phosphorus(III) acid anhydride with an aryl isocyanate (Figure 11).

650

Functions Containing an Iminocarbonyl Group P(O)(OEt)2

P(O)Ph2

ArN

ArN

P(O)(OR)2 PhSO2N

P(O)(OEt)2

P(O)Ph2

P(O)(OR)2

260

261

262

P(S)R22

P(X)R2 N2

N2 P(X)R2

P(O)(NEt2)2 PhN

P(S)R12

263

264

X = O, S R = OMe, OEt, Ph

R1 = Ph, NMe2, NPr2i

P(O)(NEt2)2

265

R2 = But, NPr2i

Figure 11

6.21.2.1.3

Iminocarbonyl derivatives with P function and one P, As, Sb, or Bi function

Since the publication of chapter 6.21.2.1.1 <1995COFGT(6)639> no major advances have occurred in this area.

6.21.2.1.4

Iminocarbonyl derivatives with one As, Sb, or Bi function and another As, Sb, or Bi function

The bis(3-valent) organometallic diazomethanes depicted in Figure 12 as 266 were prepared by treating the arsino-, stibino-, or bismuthino-dimethylamides with diazomethane. From two-step reactions of this type, mixed organometallic derivatives were also obtained. MMe2 N2 MMe2 266

M = As, Sb, Bi

Figure 12

No advances have occurred in this area since the publication of chapter 6.21.2.1.2 <1995COFGT(6)639>.

6.21.2.2

6.21.2.2.1

Iminocarbonyl Derivatives with One P, As, Sb, or Bi Function and One Si, Ge, or B Function Iminocarbonyl derivatives with one P function and one Si, Ge, or B function

(i) Silicon derivatives The well-known compounds in this class are phosphorus-containing silyldiazomethane derivatives 267 (Figure 13). Dialkylphosphanylsilyldiazomethanes (X = lone pair, R1,R2,R3Si = TMS, R4 = R5 = But), dialkylaminophosphanylsilyldiazomethanes (X = lone pair, R1,R2,R3Si = TMS, R4, R5 = dialkylamino) were prepared by reacting the lithium salt of the (trimethylsilyl)diazomethane with the desired chlorophosphanes. However, silylated -diazo phosphonates (X = O, R1,R2,R3Si = TMS, TBDMS, SiPri3, R4,R5 = OMe, OEt) and phosphonothioic

651

Functions Containing an Iminocarbonyl Group

diamides (X = S, R1,R2,R3 = TMS, SiPh3, R4,R5 = NPri2) could be obtained by reacting lithiated diazo phosphonates with corresponding silyl electrophiles (chlorides or triflates). -Diazo phosphine sulfides (X = S, R1,R2,R3Si = TMS, R4,R5 = But) and -diazo phosphonothioic diamides (X = S, R1,R2,R3 = TMS, R4,R5 = NPr2i ) were obtained by direct sulfurization of the corresponding phosphanyl precursors <1995COFGT(6)639>.

N2

S

PEt2

P(X)R4R5

P(NPr2i )2

PhN

N2

GeEt3

SiR1R2R3

267

GeEt3

268

269

R1R2R3Si = TMS, TBDMS, SiPr3i , SiPh3 R4, R5 = alkyl, dialkylamino, OMe, OEt X = lone pair, O, S Cl + P(NPr2i )2

M1Me3 N2

N2 BR – 3

270

M2Me3

M1 = Si, Ge M2 = As, Sb, Bi

271

Figure 13

(ii) Germanium derivatives Insertion reaction of phenyl isocyanide into the weak GeP bond of germanylphosphine (Et3GePEt2) led to the formation of triethylgermanium derivative 268 (Figure 13). The -diazo phosphonothioic diamide triethylgermanium compound 269 was obtained by reacting lithiated -diazo phosphonate with trialkylgermanium chloride <1995COFGT(6)639>.

(iii) Boron derivatives The only examples of this class are internal salts 270 (R = H, F) which can be prepared by oxidative ylidation of the -diazophosphane 267 (X = lone pair, R1,R2,R3Si = TMS, R4,R5 = NPri2) with CCl4 followed by reaction with boron-containing Lewis acids (BH3 or BF3) (Figure 13) <1995COFGT(6)639>. Since the publication of chapter 6.21.2.2.1 <1995COFGT(6)639> no new synthetic methods for these classes of iminocarbonyl derivatives have been described.

6.21.2.2.2

Iminocarbonyl derivatives with one As, Sb, or Bi function and one Si, Ge, or B function

The reaction of (TMS)diazomethanes (M1 = Si) with metal amides (M2 = As, Sb, Bi, R = Me, n = 3) leads to the formation of the corresponding (-diazo(TMS)methyl)dimethyl arsines, stibines, and bismuthines 271 (Figure 13). (Diazotrimethylgermanylmethyl)dimethylarsine (M1 = Ge, M2 = As, R = Me, n = 3) can be prepared similarly <1995COFGT(6)639>. No new synthetic methods for these classes of iminocarbonyl derivatives have been described since the publication of chapter 6.21.2.2.2 <1995COFGT(6)639>.

652

Functions Containing an Iminocarbonyl Group

6.21.2.3

Iminocarbonyl Derivatives with One P, As, Sb, and Bi Function and One Metal Function

6.21.2.3.1

Iminocarbonyl derivatives with one P function and one metal function

(i) Main group metals Metallation of the phosphinodiazomethane derivatives with BuLi gives corresponding lithium salts 272 (Figure 14). Treating the diazolithium salt 272 with trimethylchlorostannane provides the diazomethylstannyl compound 273 <1995COFGT(6)639>.

P(X)(NPr2i )2

P(X)R1R2

P(O)R1R2

N2

N2

N2 SnMe3

Li

272

Ag

273

277

X = O, lone pair R1, R2 = But, NPr2i

P(O)R1R2

AsMe2

N2

N2

MMe3

N2

Hg

N2

Hg N2

AsMe2

P(O)R1R2

AsMe2

281

279 M = Sn 280 M = Pb

278

Figure 14

In 1995, from the reaction of lithium salt of [bis(diisopropylamino)phosphine]diazomethane with triphenyl- and tricyclohexylchlorostannane, the diazo derivatives 274 were obtained <1995TL4231>. Photolysis of these compounds in the presence of t-butyl isocyanide afforded ketene imines 275 as depicted in Scheme 69. The reaction proceeds via rather unstable (phosphino) (stannyl)carbene which can be trapped by t-butyl isocyanide. Compounds 275 can easily be isolated after treatment with elemental sulfur, as the compounds 276 in 86–88% yield.

PR2 N2

hν R2P C SnR13

SnR13 274

But–NC

S8

R2P N R13Sn

R = Pr2i N; R1 = Ph, cyclohexyl

But 275

S R2 P N R13Sn

But 276

Scheme 69

(ii) Transition metals Metallation of the phosphinediazomethane derivatives with Ag2O or Ag(acac) and HgO or Hg(acac)2 led to the formation of diazomethylsilver (277, R1 = R2 = OMe, OEt, R1 = OMe, R2 = Ph) and bis-(diazomethyl)mercury, respectively (278, R1,R2 = OMe, OEt, Ph) (Figure 14) <1995COFGT(6)639>. No new synthetic methods for this class of iminocarbonyl derivatives have been described since the publication of chapter 6.21.2.3.1 in <1995COFGT(6)639>.

653

Functions Containing an Iminocarbonyl Group 6.21.2.3.2

Iminocarbonyl derivatives with one As, Sb, and Bi function and one metal function

Metallation of diazomethylarsines with metal amides Me3SnMe2 and Me3PbN(TMS)2 provides the corresponding derivatives 279 and 280 with trimethylstannyl and trimethylplumbyl substituents, respectively (Figure 14). Similarly, using Hg(N(TMS)2)2 as metallating agent, bis-(diazo(dimethylarsino)methyl)mercury 281 is obtained <1995COFGT(6)639>. Since the publication of chapter 6.21.2.3.2 in <1995COFGT(6)639> no advances have occurred in this area.

6.21.2.3.3

N-Unsubstituted iminocarbonyl derivatives

Although the electronic structure of HN=C(TMS)2 has been calculated, synthetic method for this class of iminocarbonyl derivatives is not reported <1995COFGT(6)639>.

6.21.2.3.4

N-Alkyl- and N-aryliminocarbonyl derivatives

There were two general methods described in chapter 6.21.3.1.2 in <1995COFGT(6)639>. First one, consisting in the insertion reaction of alkyl or aryl isocyanides into metal–metal bonds. The N-cyclohexyl derivative 282 (Figure 15) was prepared by insertion of N-cyclohexyl isocyanide into the SiSi bond of a disilane in the presence of Pd(0) or Pt(0) as a catalyst. The Pd(0)-catalyzed method was further used to synthesize a wide range of N-aryl analogs.

Me N R1R2R3Si

R SiR1R2R3

N2

SiR1R2R3

TMS

282

R1

N

Me

287

283

R = cyclohexyl, aryl

R2

SiR1R2R3 = TMS, TBDMS

Figure 15

The second method is based on a transmetallation reaction and can be applied to the synthesis of (2,6-xylimino)bissilanes 283 (Figure 15). This compound is obtained from (2,6-xylimino) (TMS)methyllithium by treatment with requisite chlorosilane. In 1994 the regioselective functionalization of bis-(trimethylsilyl)methylimines with electrophiles was described <1994SL955>. Thus, silylated azomethines 284 are readily deprotonated in THF at 78 C to give the 2-azaallyllithium compounds 285, which react further with electrophilic reagents to give functionalized silylated imino derivatives 286 (Scheme 70).

R N H

SiMe3 SiMe3

Base

R

THF, –78 °C to rt

H

R1Cl

N Li

+

284

SiMe3

R H R1

N

SiMe3

SiMe3 SiMe3

285

286 t

Base = MeLi or LIDAKOR (the superbasic mixture of LIDA /Bu OK) R = Ph, alkenyl; R2 = Me3Si, COOEt

Scheme 70

654 6.21.2.3.5

Functions Containing an Iminocarbonyl Group N-Haloiminocarbonyl derivatives

Electronic structures of the imines HalN = C(TMS)2 have been calculated, but no synthesis of this class is reported in the literature <1995COFGT(6)639>.

6.21.2.3.6

N-Aminoiminocarbonyl (diazomethane) derivatives

The following methods were described in chapter 6.21.3.1.4 in <1995COFGT(6)639>. Silylated and germylated lithiodiazomethanes undergo transmetallation reaction upon treatment with chlorosilanes and chlorogermanes to give bis(silyl)diazomethanes (287, R1 = TMS, (TMS)SiMe2, (TMS)3Si), and bis(germanyl)diazomethanes (287, R1 = R2 = GeMe3), respectively (Figure 15). Another method for preparation of these compounds involves the transfer of the diazo group from tosyl azide to the carbanion derived from bis(TMS)- or bis(germyl)methanes. In 1995 the bis(silyldiazomethyl)polysilanes 288 were prepared by lithiation of silyldiazomethane followed by coupling with the corresponding dichloropolysilanes (Figure 16) <1995JOM(499)99>.

N2 Me N2 C Si C SiMe2R Me n

RMe2Si

288

A, n = 2, R = Me

MeMe Si Si MeMe

C, n = 3, R = Me

Me Ph Me Si Si Si Me Ph Me

B, n = 3, R = Ph

MeMe Me Si Si Si MeMe Me

D, n = 4, R = Ph

MeMe Me Me Si Si Si Si MeMe Me Me

Figure 16

Diazogermylenes 289 were obtained in good yields by one-pot synthesis as described in Scheme 71 <2001AG(E)952>. These compounds were found to be promising precursors to GeC triple bonds (germynes).

ArBr

nBuLi

ArLi

GeCl2

ArGeCl

N2 ArGe C SiMe3

THF/C6H14

THF

THF

Me3SiC(N2)Li

289 Ar = 2,6

1 (R 2NCH2)2C6H3 i

R1 = Et, Pr

Scheme 71

6.21.2.3.7

N-Silyliminocarbonyl derivatives

N-silylated bis-(TMS)imines 290 (Figure 17) are formed as side products in the reaction of silaethene with silyl azides (RN3). Since the publication of chapter 6.21.3.1.5 <1995COFGT(6)639> no advances have occurred in this area.

655

Functions Containing an Iminocarbonyl Group

TMS 3

RN

SnR13

N

R N TMS

290

Me

SiMe2R2

291

Me Cu

SiR3

292

R = TMS, (TMS)2NSiMe2

Figure 17

6.21.2.4

Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function

6.21.2.4.1

N-Alkyl- and N-aryliminocarbonyl derivatives

These compounds bear resemblance to the iminocarbonyl derivatives with two metalloid functions, and are prepared in a similar manner either by insertion of alkyl and aryl isocyanides into metal–metal bonds or by transmetallation reactions <1995COFGT(6)639>. Thus, the Pd(0)catalyzed insertion of isonitriles into SiSn bond of organosilylstannanes leads to the formation of organosilyl(N-alkylimino)stannanes (291, R1,R2 = Me, R3 = Pri, C6H11, C6H13, 2-MeC6H4; R1 = Me, R2 = But, R3 = Pri; R1 = Me, R2 = But, R3 = Pri). (2,6-Xylimino) (TMS)methyllithium has been converted into copper reagents 292 by transmetallation reaction with CuBrSMe2 or Cu acetylide (Figure 17) <1995COFGT(6)639>. Recently, Xue and co-workers have studied in detail the insertion reactions of aryl isocyanides into the zirconium alkyl silyl complexes (293, R1,R2,R3 = bn) <1998OM4853> and amido silyl complexes (293, R1,R2,R3 = Me2N, R1,R2 = Me2N, R3 = (Me3Si)2N) <1999OM1002>. In case of alkyl silyl complexes the isocyanide insertion occurred exclusively into the ZrSi bond to give the product 296 as a result of silyl ligand migration (Scheme 72). Alternatively, the amido silyl complexes containing different ligands offered the opportunity to observe the competition between silyl and amido ligands in the migration step and to study whether silyl or amido ligand migration is preferred. It was found that arrangement of ligands in 293 directs the attack of the isocyanide molecule. Thus, in amido silyl complex (Me2N)3ZrSi(SiMe3)3 the trans attack to the silyl ligand results in the formation of 242. However, in case of (Me2N)2[(Me3Si)N]ZrSi(SiMe3)3, steric hindrance causes the isocyanide attack to take place cis to the silyl ligand with formation of 294 where only amide migration is feasible giving rise to the formation of 296.

6.21.2.4.2

N-Aminoiminocarbonyl (diazomethane) derivatives

As described in chapter 6.21.3.2.2 in <1995COFGT(6)639>, these compounds are obtained by metallation reactions. Reaction of silyldiazomethanes with BuLi gives lithium silyldiazomethanides (297, SiR3 = TMS, tips, TMS-SiMe2). Treatment of (TMS)diazomethane with metal amides furnishes the plumbyl- and stannyl(TMS)diazomethanes 298. The stannyl(triisopropylsilyl)diazomethane 299 can be obtained from the reaction of bis(trimethylstannyl)diazomethane with Pri3SiCl. From the reaction of lithium silyldiazomethanide with Cl2Ni(PMe3)2 and Rh(PMe3)4Cl the (diazomethyl)trimethylsilanenickel(II) complex 300 and (diazomethyl)trimethylsilanerhodium(I) complex 301 were obtained, respectively (Figure 18). Since the publication of chapter 6.21.3.2.2 in <1995COFGT(6)639> no advances have occurred in this area.

6.21.3

IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

The only compounds of this class mentioned in chapter 6.21.4 in <1995COFGT(6)639> were the organometallic complexes with bridging isocyanide ligands.

656

Functions Containing an Iminocarbonyl Group Ar ArNC R1

Si(SiMe3)3 Zr 3 R R2

Zr

R1

R2

294

R1

Si(SMe3)3 Zr 3 R R2

R1, R2 = Me2N, R3 = (Me3Si)2N

Si(SiMe3)3 Zr R3

R

R2

R3

R1, R2, R3 = bn

ArNC

1

Si(SiMe3)3

296

Isocyanide attack cis to the silyl ligand

293

C

N

Ar

N

R1

C Zr

R3

Si(SiMe3)3

C N Ar

R2

295

242

Isocyanide attack trans to the silyl ligand

R1, R2, R3 = Me2N

Scheme 72

SnMe3

SiR3

SiR3

N2

N2

N2

SiPri3

MMe3

Li

M = Sn, Pb 297

298

TMS N2

299

TMS PMe3 Rh PMe3 Me3P PMe3

N2

PMe3

Ni Me3P Cl

300

301

Figure 18

Iminocarbonyl derivatives 302 in which a C¼N double bond is bound to two Al atoms with very short AlN bond are formed by the insertion of isonitriles into the AlAl bond (Equation (30)) <1994CB1587>.

(Me3Si)2HC CH(SiMe3)2 Al Al CH(SiMe3)2 (Me3Si)2HC

i

(Me3Si)2HC Al (Me3Si)2HC

R N

302 i. RCN, n-pentane, –25 °C to rt, 1 h R = CMe3, Ph

CH(SiMe3)2

ð30Þ

657

Functions Containing an Iminocarbonyl Group

Other interesting examples of the complexes 303 which contain two different metals bound to the iminocarbonyl group are obtained by insertion of MeNC into the polar M1M2 bonds, as shown in Equation (31) <1996CC219>. Me2 Si

Me2

Tol N Me2

Me Si Si Si Me2

Cp M

N N

Tol

M1(CO)2 Tol

Si MeNC Me Si Si Si

M

Tol Me

N Me2 N N

Me2 303

N M Tol Tol

M1(CO)2 Cp

M1

Ti

Fe

Ti

Ru

Zr

Fe

Zr

Ru

Hf

Fe

Hf

Ru

ð31Þ

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Functions Containing an Iminocarbonyl Group 2000ZOR1615 2001AG(E)952 2001BMCL1749 2001CHE360 2001KGS349 2001JCS(D)1582 2001JOC2161 2001JOM11 2001OL1133 2001OL2341 2001OM1792 2001SC2351 2001SC2491 2001T1671 2001TL1259 2001TL1753 2001TL2273 2002CC2794 2002EJM285 2002JCO167 2002JOC7553 2002MI469 2002T867 2002T1739 2002T2985 2002TL49 2002TL57 2002TL565 2002TL7105 2002TL9255 2003JCS(D)2573 2003JOC1611 2003JOC2300 2003OL3851

659

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660

Functions Containing an Iminocarbonyl Group Biographical sketch

Franciszek Sa˛czewski was born in Sopot, Poland on November 18, 1951. He graduated from Medical University of Gdan´sk in 1974 with M.S. degree in pharmacy and that same year began his career at the Department of Organic Chemistry. In 1981 he received his Ph.D. and in 1988 D.Sc. degree in pharmaceutical chemistry, and in 1999 was promoted to full professor. During 1983–1984 and 1988–1989 he was working with Prof. Alan Roy Katritzky at the Department of Chemistry, University of Florida, USA. He is a member of the Royal Society of Chemistry (UK), International Society of Heterocyclic Chemistry, Polish Pharmaceutical Society, and Polish Chemical Society. Prof. F. Sa˛czewski is currently the head of the Department of Chemical Technology of Drugs, Medical University of Gdan´sk, Poland. His research interests include the design and synthesis of nitrogen-containing heterocyclic compounds with potential circulatory, anticancer, and antiHIV activities.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 605–660

6.22 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal V. D. ROMANENKO and V. L. RUDZEVICH National Academy of Sciences of Ukraine, Kiev, Ukraine 6.22.1 FUNCTIONS CONTAINING DOUBLY BONDED P, As, Sb, or Bi 6.22.1.1 General Remarks 6.22.1.2 Dicoordinate Phosphorus and Arsenic Derivatives 6.22.1.2.1 Dihalomethylenephosphines, Hal2C¼PY 6.22.1.2.2 Oxygen- and sulfur-substituted methylenephosphines, RO(X)C¼PY and RS(X)C¼PY 6.22.1.2.3 Nitrogen-, phosphorus-, and arsenic-substituted methylenephosphines, R2E(X)C¼PY (E = N, P, As) 6.22.1.2.4 Silicon- and germanium-substituted methylenephosphines, R3Si(X)C¼PY and R3Ge(X)C¼PY 6.22.1.2.5 Metallated methylenephosphines, LnM(X)C¼PY 6.22.1.2.6 C,C-diheterosubstituted methylenearsines, X2C¼AsY 6.22.1.3 Tricoordinate Phosphorus Derivatives 6.22.1.3.1 Stabilized [X2C¼PY2]+ species 6.22.1.3.2 Functions with a phosphorus–metal -donor bond, X2C¼P(MLn)Y 6.22.1.3.3 35-Methylenephosphoranes, X2C¼P(¼Z)Y 6.22.1.4 Tetracoordinate Phosphorus Derivatives 6.22.1.4.1 Dihalosubstituted ylides, Hal2C¼PY3 6.22.1.4.2 Oxygen-, sulfur-, and selenium-substituted ylides, RE(X)C¼PY3 (E = O, S, or Se) 6.22.1.4.3 Nitrogen-, phosphorus-, arsenic-, and antimony-substituted ylides, R2E(X)C¼PY3 (E = N, P, As, or Sb) 6.22.1.4.4 Silicon-, germanium-, and boron-substituted ylides, R3E(X)C¼PY3 (E = Si or Ge) and R2B(X)C¼PY3 6.22.1.4.5 Metal-substituted ylides, LnM(X)C¼PY3 6.22.1.5 Tetracoordinate Arsenic, Antimony, and Bismuth Derivatives 6.22.1.5.1 C,C-Diheterosubstituted arsonium ylides, X2C¼AsY3 6.22.1.5.2 Stibonium and bismuthonium ylides bearing heterosubstituents, X2C¼EY3 (E = Sb or Bi) 6.22.2 FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID 6.22.2.1 Tricoordinate Silicon and Germanium Derivatives 6.22.2.1.1 Diheterosubstituted silaethenes, X2C¼SiY2 6.22.2.1.2 C,C-Diheterosubstituted germaethenes, X2C¼GeY2 6.22.2.2 Functions Incorporating a Doubly Bonded Boron 6.22.2.2.1 Methyleneboranes, X2C¼B-Y 6.22.2.2.2 2-Borataallenes, [X2C¼B¼CY2] 6.22.3 FUNCTIONS INCORPORATING A DOUBLY BONDED METAL 6.22.3.1 Transition Metal–Carbene Complexes 6.22.3.1.1 N-Heterocyclic carbene complexes 6.22.3.1.2 Silicon-substituted carbene complexes, R3Si(X)C¼MLn 6.22.3.2 Functions with a Formal Tin–Carbon and Lead–Carbon Double Bond

661

662 662 662 662 664 665 668 671 673 675 675 676 677 680 680 681 681 685 686 687 687 687 688 688 688 691 693 694 695 695 696 696 702 704

662 6.22.1

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal FUNCTIONS CONTAINING DOUBLY BONDED P, As, Sb, or Bi

6.22.1.1

General Remarks

This section will survey the chemistry of functions X1X2C¼E (X1, X2 = heteroatom substituents; E = P, As, Sb, or Bi) featuring a double bond between carbon and the heavier group 15 element. The known structural types of molecules containing these functions, arranged with increasing coordination number of element, are listed below. It is the peculiar -bonding situation inducing a trigonal planar coordination around carbon which justifies the description of compounds A–C as heteroatom analogs of alkenes (Figure 1). In contrast, the compounds of the type D contain the highly polarized CE+ bond and can be considered either as ylides or as element-stabilized carbene species.

X1

X1 E X2

Y A

X2

Y E Y

+

B

X1

Z

X1

Y

X2

E X2 C

Y E Y Y D

Figure 1 Heteroatom analogs of alkenes.

6.22.1.2

Dicoordinate Phosphorus and Arsenic Derivatives

This section concerns compounds of the type X1X2C¼EY (E = P, As) with three heteroatom– carbon bonds, whatever the nature of substituent on the phosphorus or arsenic. Since the publication of chapter 6.22 in COFGT (1995) <1995COFGT(6)677>, the synthetic chemistry of phosphaalkenes and arsaalkenes has advanced dramatically. While no single review dealing specifically with C,C-diheteroatom-substituted derivatives has been published, related surveys have appeared. The most important of these are by Dillon and co-workers , Weber and co-workers <2002PS(177)1571, 2000EJI2425, 1999MI269, 1997MI1, 1996CB367, 1996AG(E)271>, Mackewitz and Regitz <1998S125>, Yoshifuji <1997BCJ2881>, and Denis and Gaumont <1994CR1413>. There have been no experimental reports as yet of C,C-diheterosubstituted stiba- and bismaalkenes of the type X1X2C¼EY (E = Sb, Bi).

6.22.1.2.1

Dihalomethylenephosphines, Hal2C¼PY

A variety of routes developed for the synthesis of these compounds is presented in Scheme 1. By far the most general synthetic strategy involves the base-induced dehydrohalogenation of dihalomethylchlorophosphines (route ‘‘a’’). This method, as well as the dehalogenation of trihalomethylchlorophosphines (route ‘‘b’’), has become standard procedure for C,C-dihalophosphaalkene production. In addition, the dehydrohalogenation of trihalomethylphosphines (route ‘‘c’’) and the thermolysis of trifluoromethyl(stannyl)phosphines (route ‘‘d’’) also provide dihalomethylenephosphines. It has to be pointed out that in contrast to the usual procedures in olefinic chemistry, only dehydrohalogenation or dehalogenation of sterically crowded phosphine precursors allows the isolation of monomeric phosphaalkenes. Although electronic factors are not totally negligible, steric factors are of primary importance for the kinetic stabilization of dihalomethylenephosphines <1997MI343, 1994ZOB1372>. Ab initio molecular orbital calculations have been applied to determine the fluorine effect on the stability of phosphaalkene F2C¼PF and its energetically low-lying rearranged isomers FC– PF2 (‘‘phosphinocarbene’’) and F3C–P (‘‘alkylphosphinidene’’). The phosphaalkene was shown to be the most stable isomer; its energy differs from that of the phosphinocarbene by 161 kJ mol1 <1997JOM(529)3, 1996MI85>. The kinetically stabilized C,C-difluorophosphaalkenes are normally prepared by gas-phase thermal Me3SnF elimination starting from F3C(R)PSnMe3 <1995COFGT(6)677, 1994CR1413>. Like alkenes, fluorine containing phosphaalkenes have a marked potential for undergoing cycloaddition reactions and, in view of the variety of 1,2- and 1,3-dipoles available, they widen the scope of the phospha-heterocycle synthesis enormously <2001ZAAC(627)1241, 1997JOM(529)177, 1995JOC7439>.

663

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Hal a Hal

b

Hal

YLi

PCl2

Hal4C/R3P

Cl P Y

–LiCl

Hal

YPHal2

Hal Hal3C P Y

–R3PHal2

B –B.HCl

R3P or BuLi –R3PHal2 or –BuHal, –LiHal

Hal Hal

c

d

H Hal3C P Y

YP(Li)H Hal4C

–LiHal

Cl F3C P Y

B . –B HHal

SnMe3 F3C P Y

Me3SnLi –LiCl

P Y

–Me3SnF

Y = preferably Alk, Ar, or R2N (routes "a", "b"), Ar (route "c"), F3C (route "d") R = preferably But or Et2N; B = DBU or Et3N

Scheme 1

Experimental details for the preparation of phosphaalkene 3 are described in Synthetic Methods of Organometallic and Inorganic Chemistry . Refluxing a solution of CHCl3, PCl3, and AlCl3 followed by treatment with MeOPCl2 gave dichloromethyl derivative 1 which on treatment with Mes*Li (Mes* = 2,4,6-tri-t-butylphenyl) gave the compound 2. The final conversion of 2 into phosphaalkene 3 has been accomplished through dehydrochlorination with DBU (Scheme 2).

CHCl3

+

i. AlCl3 ii. MeOPCl2

PCl3

Cl

Cl

Mes*Li –LiCl

P Cl

Cl

1 (42%) Cl Cl

Cl P Mes*

DBU/ THF –DBU.HCl

2

Cl Cl

P Mes*

3 (72%)

Mes* = 2,4,6-tris(t-butyl)phenyl

Scheme 2

Dillon and Goodwin have been able to prepare the phosphaalkene Cl2C¼PArf (Arf = 2,4,6tri-trifluoromethylphenyl) using a similar approach. The precursor phosphine Cl(Cl2CH)PArf was prepared by two procedures, either directly by the action of ArfPCl2 on CHLiCl2, or via the corresponding organocadmium reagent <1994JOM(469)125>. The dehalogenation route has also received further attention. A range of new phosphaalkenes including the compounds 4–6 bearing very bulky groups has been prepared in recent years by Escudie´ and co-workers <1999PS(152)153>. A variant of dehalogenation reactions should be mentioned which permits sterically crowded bis(trichloromethyl)phosphines (Cl3C)2PR (R = Mes or 2,2,6,6-tetramethylpiperidino) to be converted into phosphaalkenes 7 and 8 using (Et2N)3P <1994ZOB913>. In addition, further study has appeared of generation of the thermally unstable phosphaalkene Cl2C¼PCl <1995JOC7439>. Also reported in this study is a synthesis of the phosphaalkene precursor Cl2CHPCl2 from Cl2CHZnCl and PCl3.

664

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Cl

Cl

Cl P

Ar

P

P

Cl Ar

Cl

Cl

8

7

4, Ar = Mes

N

5, Ar = p-MeOC6H4 6, Ar = p-MeC6H4

The importance of steric protection for the stability of C,C-diiodophosphaalkenes, I2C¼PR, was investigated by varying the size of group R. The phosphaalkene I2C¼P-Is (Is = 2,4,6Pri3C6H2) could be prepared in 15% isolated yield by reaction of IsPCl2 and CHI3 with 2 equiv. of LDA, in analogy to the synthesis of the stable, sterically more protected I2C¼PMes* (Mes* = 2,4,6-But3C6H2). If the steric protection on the phosphorus was decreased further (R = Es = 2,4,6-Et3C6H2, R = Mes = 2,4,6-Me3C6H2), the substituted phosphines RP(Cl)NPri2 (R = Es, Mes) were formed as main products, in addition to thermally unstable phosphaalkenes I2C¼P-Es and I2C¼P-Mes. The reaction of I2C¼P-Mes* with bromine gave an (E)/(Z) mixture of the C-bromo-C-iodophosphaalkene Br(I)C¼P-Mes*. Further reaction with bromine proceeded via Br2C¼P-Mes* and finally led to Br(Br2CH)P-Mes* <1994RTC278>.

6.22.1.2.2

Oxygen- and sulfur-substituted methylenephosphines, RO(X)C¼PY and RS(X)C¼PY

Among the most common routes for the synthesis of these compounds are those based on elimination and silyl migration reactions (Equations (1) and (2)) <1995COFGT(6)677>. RX

Cl P Y

RX

1,2-Elimination

RX

–HCl

RX

P Y

ð1Þ

P Y

ð2Þ

X = O, S

X

TMS P Y

RX

1,3-Me3Si shift –HCl

TMS X RX

X = O, S

In an interesting extension of the 1,2-elimination methodology, it has been found that lithium bis(trimethylsilyl)phosphide reacts with an excess of dimethyl carbonate to afford the bis(1,2dimethoxyethane-O,O0 )lithiooxymethylidynephosphine 10. The phosphaalkene 9 is probably an intermediate in this reaction but it has not been detected directly (Scheme 3) <1992ZAAC(612)72>. MeO (TMS)2PLi

O

+ MeO

DME, –20 °C

(TMS)2P

OMe

LiO

OMe

LiO P MeO

TMS 9

–MeO–TMS 79%

Scheme 3

LiO C P.2DME

–MeO–TMS

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

665

The silatropic principle combined with the insertion reaction has been used to prepare the rather unstable metallophosphaalkenes 11, which decomposed to the doubly metallated 1,3,4thiadiphospholes by extrusion of (TMS)2S. However, the compounds 11 were intercepted as isolable [(CO)5Cr]-adducts 12 by treatment with [(Z)-cyclooctene]Cr(CO)5 (Scheme 4) <1997OM3188>.

[M]-P(TMS)2

CS2

TMS S

Pentane, rt

TMS S

P [M]

LCr(CO)5

TMS S

Benzene, rt

TMS S

Cr(CO)5 P [M] 12

11 [M] = Cp*(CO)2M; M = Fe, Ru

M = Fe (40%)

L = (Z )-cyclooctene

M = Ru (32%)

Scheme 4

Yoshifuji and co-workers utilized an in situ generation-capture methodology for the synthesis of phosphaalkenes (Z)-14 and 15 via reaction of the C,C-dibromophosphaalkene 13 with butyllithium and diphenyldisulfide (Scheme 5) <1998CL651>. This development was the key to further applications of the sulfur-substituted phosphaalkenes <2000CL1390>. Br Br

P Mes*

i, ii

PhS

55%

Br

13

P Mes*

i, ii

PhS

51%

PhS

Z-14

P Mes* 15

i. BunLi, THF, –100 °C; ii. PhSSPh, THF, –78 °C to 0 °C

Scheme 5

6.22.1.2.3

Nitrogen-, phosphorus-, and arsenic-substituted methylenephosphines, R2E(X)C¼PY (E = N, P, As)

(i) From C,C-dihalomethylenephosphines A kinetically stabilized phosphanylidene carbenoid (Z)-16 was prepared from the phosphaalkene 3 and butyllithium (vide infra), and was allowed to react with Ph2PCl to afford the corresponding 2-chloro-1,3-diphosphapropene (Z)-17 in good yield (78%) after silica-gel column chromatographic purification. Similarly, starting from (E)-16 and Ph2PCl, an attempt was made to synthesize (E)-17. Although NMR signals due to (E)-17 were observed in the reaction mixture, the latter was isomerized to (Z)-17 after the usual work-up procedure. The treatment of (Z-)17 with [W(CO)5(THF)] leads to the complex (Z)-18 with the metal carbonyl group at the less hindered phosphorus atom (Scheme 6) <2001CC1208>. Of the compounds of the type Hal(R2As)C¼PY, up to now 19 has been isolated from the reaction of 1-bromo-2-phosphaethenyllithium with Mes*AsF2 (Scheme 7). Further addition of nbutyllithium to 19 at 90 C led to the organolithium intermediate, which lost LiF to give in nearly quantitative yield the arsaphosphaallene Mes*-As¼C¼P-Mes* <1998OM1631>.

(ii) Synthesis by condensation reactions The starting point for the now extensive chemistry of the C,C-bis(dialkylamino)methylenephosphines was the synthesis of (R2N)2C¼P-TMS via the condensation of (TMS)3P with (R2N)2CF2 <1995COFGT(6)677>. The generality of this approach is restricted, however, by possible difficulty in the preparation of the requisite geminal difluorides <2002CC1618>. An alternative route to the phosphaalkene 20a is provided by the reaction of S-methyl

666

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

Li P Mes*

Cl

Ph2P

Ph2PCl 78%

Cl

P Mes*

39%

(Z )-17

(Z )-16

Cl

(Z )-18

Cl

Ph2PCl

P Mes*

Li

W(CO)5 Ph2P P Cl Mes*

W(CO)5(THF)

Ph2P

(E )-16

P Mes*

(E )-17

Scheme 6

BunLi

Li

Et2O, –100 °C

Br

Br Br

P Mes*

F Mes* As

Mes*AsF2

P Mes*

27%

Br

13

P Mes*

19

Scheme 7

bis(dimethylamino)thiouronium iodide with lithium bis(trimethylsilyl)phosphide (Equation (3)). Spontaneous condensation occurred upon mixing of equimolar amounts of the reagents in a mixture of pentane and 1,2-dimethoxyethane <1995S158, 2000EJI1185>. -X+ Me2N SMe

I–

Me2N

(TMS)2PLi.DME

Me2N

–LiI, –MeS–TMS, –DME 73%

Me2N

P

ð3Þ TMS

20a

(iii) Synthesis via free carbenes It has been demonstrated that N-heterocyclic carbenes are sufficiently nucleophilic to depolymerize cyclopolyphosphines such as (PPh)5 and (PCF3)4 and produce compounds of the type 21, which can be formulated either as phosphaalkenes or as carbene–phosphinidene complexes (Equation (4)) <1997CL143, 1997IC2151>. The latter formulation is favored by the observation that treatment of the compounds 21 with boranes results in the formation of P,P-bis(borane) complexes, indicating the availability of two lone pairs at phosphorus <1997CC981>.

R2

R1 N

R2

N R1

+

1/x (R3P)x

THF, rt

R2

R1 N

R2

N R1

R2 P R3

R2

21a–21c 21

R1

R2

R3

a

Me

Me

Ph

b

Mes

H

Ph

c

Mes

H

CF3

R1 N – + P N R3 R1

ð4Þ

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

667

It is also possible to prepare bis(amino)phosphaalkenes by direct reaction of a nucleophilic carbene with dichlorophenylphosphine. This approach is illustrated in Equation (5) for the saturated 1,3-dimesitylimidazolin-2-ylidene <1997IC2151>. The generality of this methodology is restricted, however, by difficulties in the preparation of the starting carbene. Mes N

Mes N

2

+

PhPCl2

+

P THF, rt, 1 h

N Mes

69%

Mes N+ Cl N Mes

N Ph Mes

Cl–

ð5Þ

(iv) Derivatization of P-hydrogen- and P-silyl-methylenephosphines P-Hydrogen- and P-silyl-substituted phosphaalkenes of the type R2N(Y)C¼PX (X = H, TMS) are important reagents for the introduction of R2N(Y)C¼P groups into organic molecules via electrophilic substitution at the dicoordinated phosphorus atom. In particular, treatment of the easily accessible phosphaalkene Et2N(F)C¼PH ((E)/(Z) = 18/82) with halophosphines and haloarsines in the presence of triethylamine as base provides a route to the P-phosphino and Parsino derivatives Et2N(F)C¼P-ER2 (E = P, As) <1996ZN(B)778>. 1-Diethylamino-1-fluoro-2phosphaalkenes of the type Et2N(F)C¼P-ER3 [R3E = TMS, Me3Ge, (F3C)3Ge and Me3Sn) are prepared in moderate yields by reaction of Et2N(F)C¼PH with R3EX (X = Cl, I). The relatively stable derivative Et2N(F)C¼P-TMS was used as a substrate for reactions with pivaloyl, adamantoyl, and benzoyl chloride, respectively, which by cleavage of the Si–P bond yield the ‘push/pull’ phosphaalkenes Et2N(F)C¼P-C(O)R (R = But, Ad, Ph) <2000ZAAC(626)1141>. Similarly the phosphaalkene 20a was transformed into the P-acyl derivatives (Me2N)2C¼PC(O)R (R = But, Ph) when allowed to react with an equimolar amount of pivaloyl or benzoyl chloride <1998OM3593>. The phosphaalkenyl functionalized carbyne complexes 23 have been obtained by reacting the chlorocarbyne complexes 22 and P-silylated phosphaalkenes 20 (Equation (6)) <1997CB1305>. The reaction of 20 with Cp*(CO)2MBr (M = Fe, Ru) in hydrocarbon solvents at room temperature affords moderate yields of the metallophosphaalkenes 24 (Equation (7)) <2000EJI1185, 1993ZN(B)1784>. R2N

R2N +

P

Cl

C

M(CO)2Tp'

TMS

R2N

P –TMS–Cl

R2N

C M(CO)2Tp'

22

20a, b

ð6Þ

23

Tp' = HB(3,5-Me2C3HN2)3; M = Mo, W; R = Me (a), Et (b)

R2N

R2N P R2N

+ TMS

OC

M

Br CO

20a, b

32–69%

R2N

P M OC CO

ð7Þ

24

M = Fe, Ru; R = Me (a), Et (b)

(v) Miscellaneous C-Phosphino-phosphaalkenes 25 are formed in the thermal ring opening of diphosphiranes, a theoretical study suggesting the intermediacy of diradical species <1994IC596>. In the presence of either boron trifluoride or triflic acid, the diphosphapropene 26 gives the diphosphaallylic cation 27, which is then transformed into the four-membered ring system 28. In the presence of a base, the latter converts to the three-membered system 29 <1994JA6149>.

668

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

R2N P P

P Mes* R2N

Cl 25

NR2

NR2

+

(R2N)2P

R2P

P

P NR2

R2N

NR2

26

27

+

N R

P NR2

NR2

+

P P

NR2

R 28

29

On heating in toluene the 1,3-diphosphacyclobutane-2,4-diyl 30 isomerizes by cleavage of the PC bond to give the diphosphapropene 32. A plausible intermediate of this reaction is the phosphinocarbene 31, which results from a ring opening and stabilizes by CH activation of an ortho-positioned t-butyl group to give 32 (Scheme 8) <1995AG(E)555>. Cl X Mes* P

P *Mes X Cl

Toluene, 100 °C

P

P *Mes

Mes* P Cl

H Cl

Me Me

31

30

Mes* P

Cl

Cl

32

Scheme 8

6.22.1.2.4

Silicon- and germanium-substituted methylenephosphines, R3Si(X)C¼PY and R3Ge(X)C¼PY

The heavier group 14 elements, especially silicon, exert a stabilizing effect on the methylenephosphine function and consequently numerous C-silyl-substituted phosphaalkenes have been synthesized and thoroughly studied. The development of C-germylated phosphaalkenes has proceeded at a slower pace and has not yet reached the degree of complexity of its silicon counterparts. However, in the 1990s a range of C-germyl-substituted phosphaalkenes has become available, and recent works have demonstrated that many of these compounds exhibit excellent thermal stability.

(i) From C,C-dihalomethylenephosphines A halogen–metal exchange/coupling route is the most effective for the preparation of highly functionalized phosphaalkenes R3E(Hal)C¼PY (E = Si, Ge) as it permits a chemical variation of the substituent pattern with retention of the P¼C unit. Several examples of the use of this strategy have been reported. For example, addition of n-butyllithium to the phosphaalkene 13 at low temperature with subsequent quenching the resulting lithio derivative with chlorotrimethylsilane furnished (Z)-33 in 98% isomeric purity <1996OM174>. Conversion of the phosphaalkene (Z)-33 to the corresponding lithio derivative with n-butyllithium, followed by the addition of 1,2-dibromoethane produced the silylated species (E)-33 as the only isomer (Scheme 9) <1997JOM(529)107>. A similar approach has been used for the preparation of C-germyl substituted phosphaalkene 34. The best yield in 34 was obtained when the reaction mixture was stirred for 1 h at 80 C, after addition of the difluorogermane to 13 at 100 C. The phosphaalkene 34 can also be obtained in one pot by adding 2 equiv. of BunLi to a mixture of 13 and Mes2GeF2 in Et2O since at 120 C butyllithium does not react with the GeF bond of difluorodimesitylsilane (Equation (8)) <1996OM3070>.

Br Br

P Mes* 13

i. BunLi ii. TMS-Cl –130 °C

i. BunLi TMS Br

P Mes*

(Z )-33 (90%)

Scheme 9

ii. BrCH2CH2Br

Br

THF, –110 °C

TMS

P Mes*

(E )-33 (60%)

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal i. BunLi ii. Mes2GeF2

Br P Mes*

Br

13

669

F Mes2Ge

ð8Þ

P Mes*

Et2O, –100 °C 35%

Br 34

The carbenoid Cl(Li)C¼PMes*, which is much more stable than its bromo analog, has also been shown to behave as a nucleophile when treated with halogermanes. Thus, reaction of 2-phosphaethenyllithium with difluoro(mesityl)(fluorenyl)germane afforded the fluoro(germyl)phosphaalkene 35 in 77% yield. In contrast, the chloro analog 36 was obtained only in very low yield (10%). However, the phosphaalkene 36 could be prepared in good yield by a two-step procedure involving the prior reaction of the carbenoid Li(Cl)C¼P-Mes* with trichloromesitylgermane, followed by the addition of fluorenyllithium <1999OM1622>. As a further development of this work the synthesis of germylphosphaalkene 38 has been achieved starting from dichlorophosphaalkene 3 and difluorogermane 37 (Scheme 10) <2002JOM(643/644)202>.

i. BunLi ii. Mes(R2CH)GeX2

Cl P Mes*

Cl

X Mes Ge R2HC P Cl Mes*

THF, –78 °C

3

35, X = F 36, X = Cl

i. BunLi ii. MesGeCl3

Tip(But)GeF2

R2CHLi

THF, –78 °C

37 Tip But Ge F P Cl Mes*

Mes Cl2Ge P Mes*

Cl

38 ; Tip = 2,4,6-Pr3i C6H2; Mes* = 2,4,6 = Bu3t C6H2

R2CH =

Scheme 10

(ii) By elimination reactions An example from recent literature includes an improved procedure for the preparation of Pchloro-bis(TMS)methylenephosphine 39 (Scheme 11) .

TMS Cl TMS

i. Mg ii. PCl3

TMS

Et2O/THF

TMS

PCl2

Et3N

TMS

Et2O, rt 70%

TMS

P 39

Scheme 11

Cl

670

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

(iii) By derivatization of P-halo-C,C-bis(TMS)methylenephosphines A very useful technique for the direct introduction of the (TMS)2C¼P moiety into a variety of molecules is based on the nucleophilic substitution at the dicoordinated phosphorus atom. Phosphaalkenes (TMS)2C¼P-Y (Y = Hal, TfO) are particularly useful for the creation of new phosphorus–carbon and phosphorus–heteroatom bonds. The nucleophiles more commonly employed are Grignard and organolithium reagents as well as R2N, RO, RS, and R2P anions <1995COFGT(6)677>. However, progress has recently been made with functionalized nucleophilic species. Recent work has shown that 2,2-bis(TMS)-1-phosphaethenyl substituted pyridines 41 may be prepared by the reaction of lithium salt of the bifunctional carbanions 40 with phosphaalkene 39 (Equation 9) <2002AG(E)3367>. TMS P TMS

R

+ Cl

R

R

N Li

Et2O, –78 °C

Li

39

TMS

R

N P

P

TMS

40

TMS

ð9Þ

TMS

rac/meso-41 R = Ph, TMS

Particular success was achieved using heteroatom nucleophiles as the substrates. Treatment of 39 with 2 equiv. of (TMS)2PLi in DME gave lithium salt of 1,2-diphosphapropenide 42 in 76% yield. Subsequent reaction of 42 with additional (TMS)2PLi provides a route to the 2,3,4-triphosphapentadienide system 43, an intermediate for the synthesis of heterocyclic phosphorus compounds <1996AG(E)313>. Reactions of equimolar amounts of (5-C5Me5)(CO)2Fe-E(TMS)2 (E = P, As) with 39 afforded the 1-metallo-1-phospha(arsa)-2-phosphapropenes 44 <1995CB665, 1996CB219>.

TMS

TMS TMS

P P

TMS

TMS

Li+(DME)

TMS

TMS

TMS

TMS

P

P P

P

Li+(DME)

Fe(CO)2(Cp*-η5) E TMS

44 (E = P, As) 42

43

Reaction of 39 with AlCl3 in the presence of Ph3P results in the formation of the phosphine adduct of a methylenediylphosphenium cation 46. A similar product 47 containing the same cation was obtained by treatment of the phosphaalkene 45 with Ph3P. Finally, the phosphaalkene 46 reacts with (Ph3P)2Ni(COD) to give the complex 48 via a phosphine shift from phosphorus to the metal (Scheme 12) <1994JA2191>.

TMS P TMS

Y

AlCl3, Ph3P

TMS

Y = Cl

TMS

P + AlCl4 PPh3

–

46

39, Y = Cl 45, Y = TfO

Ph3P Y = TfO

TMS P TMS

+

TfO–

PPh3

(Ph3P)2Ni(COD)

TMS

–COD

TMS

47

–

AlCl4

+

P Ni(PPh3)3 48

Scheme 12

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

671

Fischer-type carbene pentacarbonyltungsten complexes, which are functionalized by the bis(TMS)methylenephosphino moiety bonded to oxygen 49 or nitrogen 50, are synthesized by reaction of the O-Li and N-Li precursor carbene complexes with 39 (Equation (10)) <2000JOM(613)56>. Concerning the last example, it is worth noting that metallaheterobutadiene species of the type 50 easily rearrange into 2H-azaphosphirenes <2000EJI1253, 2001JOM(617/ 618)423, 2002JOM(643/644)253>.

TMS

TMS

XLi P

TMS

+

(OC)5W

Cl

Ph

Et2O, –30 °C

Ph P

TMS

W(CO)5

X

ð10Þ

49, X = O

39

50, X = NH

(iv) Miscellaneous Dichlorophosphino ylide TMS(Cl2P)C¼PPh3 loses a chloride ion to Lewis acidic metal chlorides (AlCl3, GaCl3, and SnCl4). In the (E)- and (Z)-isomers so generated, a considerable part of the phosphenium charge is transferred to the phosphonium center leading to a phosphaalkene structure 51 <1996HAC355>. So far, very little is known about compounds containing a Ge2C¼PY backbone. In view of this, it is interesting to note that in the absence of trapping reagent, the germaphosphaallene Mes2Ge¼C¼P-Mes* gives two types of dimers: the ‘‘classical’’ head to tail dimer 52 and the dimer 53 due to cycloaddition between a Ge¼C and a P¼C double bond. The dimer 53 is the major product <1996OM3070>.

R

TMS +

P Cl

Ph3P

P R

R P – MCln

51 MCln = AlCl4, GaCl4, SnCl5

6.22.1.2.5

R Ge

Ge R R 52 R = 2,4,6-But3C6H2

R Ge R

R P P R Ge R R 53

R = 2,4,6-But3C6H2

Metallated methylenephosphines, LnM(X)C¼PY

These have been intensively studied in the last few years because of their potential as synthetic blocks in organic chemistry <1995CB465, 1996OM174, 1998CL651>.

(i) Phosphaalkenyl metal species The compounds M(Hal)C¼PY are the phosphorus analogs of alkylidene carbenoids and useful synthons for novel C-functionalized phosphaalkenes (vide supra). Halogen–lithium exchange reactions provide the most general method for the preparation of phosphaalkenyllithium derivatives. Recently new developments in this area have been reported. Treatment of THF or DME solutions of the phosphaalkene Cl2C¼PMes* 3 with excess n-butyllithium afforded cleanly the corresponding carbenoid as DME-solvate ((Z)-54a) or THFsolvate ((Z)-54b). (E)-54 was generated analogously by metallation of (E)-Cl(H)C¼P-Mes* with excess BunLi and identified by 31P NMR spectroscopy. Unlike the (Z)-isomer, (E)-54 was found to be unstable under reaction conditions and decomposed to give Mes*C¼P and Mes*(Li)C¼PBun as main products <1999JA519>.

672

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal (solv)n Li

Cl P Mes*

Cl

P Mes*

(solv)n Li

(E )-54 (solv = THF, n = x)

(Z )-54a (solv = DME, n = 2) (Z )-54b (solv = THF, n = x)

The phosphaethenyllithium reagent 54 was transmetallated with MgBr2, ZnCl2, and HgCl2 to furnish the new carbenoids 55. Bis(phosphaalkenyl)–metal species 56 can be made by reacting (Z)-54 with 0.5 equiv. of the metal halide (Scheme 13). The stability order of the newly formed phosphavinylidene carbenoids corresponds to the expected sequence Li < Mg < Zn < Hg. Whereas (Z)-54 decomposes at temperatures above 50 C, the magnesium carbenoids 55a and 56a slowly decompose at 15 C. The zinc carbenoids 55b and 56b are stable at room temperature for at least a few days. The mercury carbenoids 55c and 56c are the most stable one; they can be stored at room temperature in the air <1996OM174>. Li Cl

XM

MX2

P Mes*

THF, –110 °C

P Mes*

Cl

(Z )-54

55a–55c MX = MgBr (a), ZnCl (b), HgCl (c)

Mes*

Cl P

0.5 MX2

M THF, –110 °C

P Mes*

Cl 56a–56c

M = Mg (a), Zn (b), Hg (c)

Scheme 13

Bromium–lithium exchange at 90 C between (Z)-Br(TMS)C¼PMes* and BunLi furnished ((E)/(Z))-Li(TMS)C¼PMes* ((E)/(Z) = 1:1). Transmetallation of the latter with MgBr2 or ZnCl2 furnished only the trans-metal isomer of XM(TMS)C¼PMes* (MX = MgBr, ZnCl) <1996OM174>. A convenient synthesis of 1-arylthio-2-phosphaethenyllithiums (Z)-57 is based on brominelithium exchange of (Z)-14 with n-butyllithium. During the reaction, the (E)/(Z)-isomerization was observed even at 100 C in THF. Treatment of (Z)-57 with 0.5 equiv. of HgCl2 in THF affords the corresponding organomercury compounds 58. The transmetallation with CuCl2 gives the 1,4-diphospha-1,3-butadiene derivatives 59 as homocoupled products presumably via the corresponding phosphaalkenylcopper species (Scheme 14) <2000CL1390>.

(ii) Bridging aryl isocyaphide ligands Weber and co-workers <1993ZAAC(619)1759> reported the synthesis of a diiron complex 60 with a bridging CPR ligand in which the aryl isocyaphide is C-bonded to two metal atoms (Equation (11)). S Me

OC Fe Cp

+ CO

Fe Cp O

Mes*P(TMS)H, DBU –TMS–SMe, –DBU.H+

P

OC Fe Cp

Mes* CO Fe Cp

O 60

ð11Þ

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal ArS P Mes*

Br

BunLi

ArS

THF, –100 °C

Li

(Z )-14

673

Li P Mes*

–100 °C

P Mes*

ArS

(E )-57

(Z )-57

Ar S

0.5 HgCl2 60–79%

P Mes* Hg

Mes* P

S Ar 58

CuCl2

Cu P Mes*

ArS

O2 38–84%

Ar = Ph, 4-MeC6H4

Ar Ar

Mes* P

S S

P Mes* 59

Scheme 14

Further consideration has been given to the semi-bridging isocyaphide platinum complexes 63 <1994OM2454, 1994OM2444>. The syntheses of 63 begin with the platinum complexes 61, whose preparation was reported previously <1993OM4265>. Although no intermediates were observed by 31P NMR spectroscopy during the reaction with Pt(PEt3)4, a possible mechanism for the formation of 63 could involve intermediates 62 resulting from oxidative addition of the C-Hal bond to Pt(PEt3)4. Loss of PEt3 from this intermediate followed by PtPt bond formation would give the final product. Complexes 63 were also prepared by the direct reaction of Cl2C¼PMes* with 2 equiv. of Pt(PEt3)4 in benzene at room temperature but the yield (<40%) was much lower than that obtained from the reaction of 61 with Pt(PEt3)4 (Scheme 15).

Hal L

Pt

Hal

L

PtL4 P Mes*

Hal

Benzene, rt

L L Hal

Pt Pt

Hal

L

L

P Mes*

L –L 60–65%

Pt

L P Mes*

Hal Pt L

61 62

63

Hal = Cl, Br; L = Et3P

Scheme 15

6.22.1.2.6

C,C-diheterosubstituted methylenearsines, X2C¼AsY

In comparison with C,C-diheterosubstituted phosphaalkenes, the area of corresponding molecules with an arsenic–carbon double bond is rather poorly explored. Even so, since 1994 various methods for the synthesis of hetero substituted arsaalkenes have been developed. Some of them mirror the methods elaborated for the synthesis of the related phosphaalkenes. As shown in Scheme 16 the action of some lithiated halomethanes on Mes*AsF2 affords arsaalkenes halogenated at the alkene carbon atom. Thus, the dibromoarsaalkene 64 was prepared by a one-pot synthesis from an aryldifluoroarsane and LiCHBr2. The C,C-dichloro- and C,C-diiodo-arsaalkenes 65 and 66 were prepared by a similar route from Mes*AsF2 and, respectively, LiCCl3 and LiCI3. However, in contrast to the synthesis of 64, in which 2 equiv. of LiCHBr2 was required, only 1 equiv. of LiCCl3 and LiCI3 was used; the formation of 65 and 66 from the probable intermediates X3CAs(F)Mes* was effected by addition with a second equivalent of n-butyllithium at 90 C <1996OM2683>.

674

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

Mes* AsF2

LiCHBr2

Br

THF, –100 °C

Br

F As Mes*

LiCHBr2

Br

46%

Br

As Mes* 64

Hal Hal Hal

LiCHal3 THF, –90 °C

F As Mes*

BunLi

Hal

56–64%

Hal

As Mes*

65, Hal = Cl Mes* =

66, Hal = I

2,4,6-Bu3t C6H2

Scheme 16

[1,3]-Silyl migration in combination with the preceding addition reaction, described for the synthesis of phosphaalkenes, can also be used to obtain arsaalkenes. Thus, the reaction of the metalodisilylarsanes Cp*(CO)2M-As(TMS)2 (M = Fe, Ru) with carbon disulfide furnished the metaloarsaalkenes (TMS-S)2C¼P-M(CO)2Cp* as isolable compounds in yields up to 80% <1997OM3188>. The reaction of (CF3)2AsH with secondary amines in a molar ratio of 1:3 allows the preparation of C-fluoro-C-aminoarsaalkenes 68a–68c in 15–35% yield. The main product of the reaction with dimethylamine is the bis(amino)methylenearsine 69a. With Et(Pri2)NH or Pri2NH the corresponding derivatives F[Pri(Et)N]C¼As-CF3 68d and F(Pri2N)C¼P-CF3 68e, respectively, are formed only in traces 68d, or not at all 68e. The synthesis is assumed to involve an initial base-assisted HF elimination to the transient 2-arsaperfluoropropene 67. This step is seriously hindered for the bulky amines and the formation of the corresponding arsaalkenes 68d,68e is suppressed. Evidence for this idea is provided by the direct conversion of 67 into [Pri2(Et)N]2C¼As-CF3 69d and (Pri2N)2C¼PCF3 69e by exposure to the respective amines (Scheme 17) <1995ZN(B)94>. F

(CF3)2AsH

R2NH

F

–60 °C

F

As CF3 R2N 68a–68c 2R2NH

As CF3

+ R2N

67

R2N 68, 69

a

b

c

d

e

R2N

Me2N

Me(Et)N

Et2N

Et(Pri)N

Pr2iN

As CF3

69a–69e

Scheme 17

The C,C-bis(amino)arsaalkene 70 have been obtained from the reaction of LiAs(TMS)22THF with a thiuronium iodide (Equation (12)). Spontaneous condensation occurs upon mixing of reagents in pentane to give 70 as orange oil in 78% yield <1996CB367>. Condensation of Tp0 (CO)2MCCl (M=Mo, W; Tp0 = HB(3,5-Me2HC3N2)3) with the arsaalkene 70 afforded the novel arsaalkenyl carbyne complexes Tp0 (CO)2MC-As¼C(NMe2)2 (M = Mo, W) <1999OM4603>. Another type of periphery reaction takes place when the arsaalkene 70 is treated with (5-Cp*)(CO)2FeBr n-pentane. Microcrystalline brown metaloarsaalkene (5-Cp*)(CO)2Fe-As¼C(NMe2)2 is isolated in 44% yield <1996CB223>. +

Me2N SMe Me2N

I–

LiAs(TMS)2.2THF 78%

Me2N As TMS

Me2N 70

ð12Þ

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

675

The reaction between nucleophilic carbenes and pnictinidene oligomers described in Section 6.22.1.2.3 also occurs in the case of arsenic. 1,3-Dimesitylimidazol-2-ylidene reacts with hexaphenylcyclohexaarsane to form the arsaalkene 71. The reaction appears to tolerate strongly -electron-withdrawing substituent on arsenic. For instance, the arsaalkene 72 was obtained in 61% yield by reacting 1,3-dimesitylimidazol-2-ylidene with tetrakis(pentafluorophenyl)cyclotetraarsane (Equation (13)) <1997IC2151>. Mes N +

Mes N As N R Mes

1/x (RAs)x THF, rt

N Mes

ð13Þ

71, R = Ph 72, R = C6F5 R = Ph, x = 6; R = C6F5, x = 4

With the arsaalkene 64 as starting material, the new C-bromo-C-silyl-substituted arsaalkene 73 was obtained by successive reaction with n-butyllithium and chlorotrimethylsilane (Scheme 18). The air-stable 73 can be further functionalized by means of Li/Br exchange <2002OM1531>. In a similar way, treating 64 with n-butyllithium in ether at 90 C and then with Mes*AsF2 gave the arsaalkene 74 which is a valuable precursor for the synthesis of 1,3-diarsaallene Mes*As¼C¼As-Mes* <2000JA12880>.

Br Br

BunLi As Mes*

THF, –90 °C

Li Br

TMS-Cl

As Mes*

–90 °C

TMS Br

64

As Mes* 73

Mes* F As As Br Mes*

Mes*AsF2

74

Scheme 18

6.22.1.3 6.22.1.3.1

Tricoordinate Phosphorus Derivatives Stabilized [X2C¼PY2]+ species

Several synthetic routes to the methylenephosphonium ions have been developed, but each one is appropriate for only a limited number of substrates <1997ACR486>. The most general synthesis is based on the heterolytic cleavage of a PCl bond in compounds of the type X2C¼P(Cl)Y2. Thus, the attack of AlCl3 on the PCl bond in the ylide 75 generates the methylenephosphonium salt 76 (Equation (14)) <1992AG(E)99>. The limitation of the method is illustrated by the reaction of ylide 77 with GaCl3 which affords the covalent complex 78 and not the corresponding methylenephosphonium salt (Equation (15)) <1995OM3762>.

TMS TMS

Cl P But But 75

AlCl3

TMS

CH2Cl2 80%

TMS

+ P

But But

76

AlCl4–

ð14Þ

676

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

Cl P NR2 NR2

Cl + P(NR2)2

GaCl3

– GaCl3

ð15Þ

78

77

At least in a very formal sense, one can consider the compounds 79 produced by reaction of the metallophosphaalkene 24a with trifluoromethanesulfonates as methylenephosphonium derivatives, although it is obvious that the real bonding pattern of these species is much closer to the phosphanyl-substituted carbenium salts (Equation (16)) <1999OM4216>. Me2N

Me2N

F3CSO2OR

+

Me2N

R

Me2N + Me2N

P

P Me2N

[Fe]

[Fe]

R P [Fe]

F3CSO–3

24a

ð16Þ

79 [Fe] = Cp*(CO)2Fe; R = Me, Me3SiCH2, Me3Si

6.22.1.3.2

Functions with a phosphorus–metal s-donor bond, X2C¼P(MLn)Y

Basically, three strategies are used for the preparation of the title compounds: (i) complexation of a metal species with a phosphaalkene which already possesses the P¼C double bond <1988CRV1327, 1997BSJ2881>; (ii) the ‘‘phospha-Wittig route’’ <1992ACR90>, and (iii) an approach based on the reactions of terminal phosphinidene complexes <1994CRV1413>. The C,C-dihetero-substituted species are usually obtained via the complexation of free phosphaalkenes. Examples from recent literature are presented in Equations (17)–(19) <1999EJI1607, 2002EJI3272, 2001CC1208>. Me2N E Me2N

[Fe]

MMe3

Me2N

n-Pentane, –78 °C 41–59%

Me2N

MMe3 E [Fe]

ð17Þ

E = P, As; [Fe] = Cp*(CO)2Fe; M = Al, Ga, In; <1999EJI1607>

Me2N

(Ph3P)AuCl P

2 Me2N

Me2N

THF, rt 85%

H

H

NMe2 +

P Au

NMe2

P Me2N

Cl–

ð18Þ

H

<2002EJI3272> Cl Ph2P

Mes* P

W(CO)4(COD) 19%

Cl

Mes* P Ph2P W(CO)4

ð19Þ

<2001CC1208, 2002PS(177)1609>

Several phosphaalkene transition metal complexes have been prepared by the reaction of free phosphaalkenes with Fischer carbene complexes. Thus, treatment of the phosphaalkene 39 with in situ generated carbene complex anions results in stereoselective P–C coupling to form 2-phosphabutadiene complexes 80 and 81 (Scheme 19) <1997AG(E)1095>. When the chromium- and tungsten-[ethoxy(phenyl)methylene] complexes were combined with the phosphaalkenes (Me2N)2C¼PR (R = But, TMS), the phosphaalkene complexes 82 and 84 were isolated in 47–55% yield by fractioning crystallization. The complexes 83 and 85 were also formed, but they cannot be separated from the alkene 86 without decomposition (Scheme 20) <2001CEJ5401>.

677

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal OEt

i. BunLi ii. (TMS)2C=PCl 39

OEt (OC)5M

Et2O, –78 °C

Ph

TMS

Ph

(OC)5M TMS P

M(CO)5 H

P H

TMS EtO

TMS

Ph

80, M = Cr (49%) 81, M = W (76%)

Scheme 19

OEt

(Me2N)2C=P–R

Me2N

EtO

R P

(OC)5M Ph

n-Pentane, –40 °C Me2N

M = Cr, W

M(CO)5

R P

+ Ph

EtO

NMe2

Ph

NMe2

+ M(CO)5

82, R = But

83, R = But

84, R = TMS

85, R = TMS

86

Scheme 20

Treatment of (Me2N)2C¼P-Fe(CO)2Cp* 24a with [(OC)5Cr¼C(OEt)Ph] led to the formation of [Cp*(CO)4Fe2] as the main product. The complex [Cp*(OC)2FeP{Cr(CO)5}¼C(NMe2)2] was isolated in 10% yield <1998CEJ469>.

6.22.1.3.3

s 3l5-Methylenephosphoranes, X2C¼P(¼Z)Y

Progress in the chemistry of -bonded three-coordinate pentavalent phosphorus compounds has been reviewed <1997CCR(158)275>. Since their discovery in 1974 hundreds of stable 35phosphoranes have been synthesized and thoroughly investigated. Early work concentrated on preparation of various structural types of monomeric Q¼P(¼Z)Y compounds. More recently the chemistry of functionalized 35-bis(ylene)phosphoranes has been developed, resulting both in valuable new reactions and synthetically useful, highly reactive polyfunctional 35-P reagents.

(i) From organodichlorophosphines Experimental details for the preparation of [(TMS)2C¼]2PCl from MeOPCl2, Li(Cl)C(TMS)2 and BCl3 are described in Synthetic Methods of Organometallic and Inorganic Chemistry <1996MI82>. A successful alternative approach to the title compound utilizes reactions of the monomeric bis(trimethylsilyl)methylenephosphines (vide infra). The ferrocenyl-substituted bis(methylene)phosphorane 87 was synthesized in 52% yield by addition of 3 equiv. of bis(trimethylsilyl)methylenecarbenoid to ferrocenyldichlorophosphine (Scheme 21). The X-ray structure of 87 shows some unusual structural features, which indicate considerable electronic interaction of the ferrocenyl group and the 35-phosphorane unit <1997JOM(541)237>.

TMS

TMS

TMS Cl2P

2Li(Cl)C(TMS)2 Fe

THF-Et2O,n-C5H12

TMS P

Li(Cl)C(TMS)2 Fe

52%

P TMS TMS

–100 °C 87

Scheme 21

Fe

678

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

(ii) From methylenephosphines and iminophosphines The preparation of X2C¼P(¼Z)Y compounds by 1,1-oxidative addition reactions to dicoordinated phosphorus species is currently the method of choice in the synthesis of many types of 35-P derivatives. For example, Niecke and co-workers have successfully used this approach to prepare dichloromethylene(imino)phosphorane 89, which on lithiation with n-butyllithium gave the iminophosphoranylidene carbenoid 90 (Scheme 22) <1994AG(E)982>. The application of the same protocol to the phosphaalkene 91 led to the bis(methylene)phosphorane 92. However, the attempt to extend this strategy to prepare the dibromomethylene compound 93 by treatment of 91 with bromoform and n-butyllithium produced only a 10% yield of the desired product. A more satisfactory result was obtained in a modified procedure which involved the use of potassium t-butoxide as base and afforded 93 in 91% yield. The oxidation of 91 into 94 by a chlorofluorocarbene moiety was achieved by addition of a mixture of 91 and CFCl3 to a titanium(0) suspension (Equation 20) <1995AG(E)1849, 1999JA5953>.

Cl Mes* N P

CCl4 /BunLi THF, –105 °C 45%

Mes* 88

Cl

Li Cl

BunLi P Mes*

P Mes* Mes* N

Mes* N

90

89

Scheme 22

X2 TMS TMS

i or ii or iii P Mes*

X1 P Mes* TMS TMS

91 92, X1 = X2 = Cl

ð20Þ

93, X1 = X2 = Br 94, X1 = F, X2 = Cl i. CHCl3/BunLi, THF/Et2O, –100 °C; ii. CHBr3/ButOK, hexane, 0 °C; iii. TiCl4/LiAlH4/CFCl3, THF, –78 °C

Treatment of 91 with dimethylsulfonium methylide cleanly afforded the bis(methylene)phosphorane 95. Subsequent reaction of 95 with n-butyllithium proceeded via H/Li exchange to give the phosphoranylidene ylide 96, which was isolated as highly air- and moisture-sensitive crystals (Scheme 23). The compound 96 may be easily transformed into new organometallic derivatives with retention of the low-coordinate phosphorus center <1997JA12410>. A variation on the same theme was also provided by the synthesis of the methylenephosphorane 98 containing a CH2 moiety at an sp2-hybridized P(V) center. While compound 98 is stable at ambient temperatures, it easily isomerizes by heating a toluene solution at 100 C to give the corresponding methylene(imino)phosphorane 99 (Scheme 24) <1997CC293>.

Li(THF)3

H TMS TMS

P Mes*

Me2S=CH2

H

BunLi P Mes*

TMS TMS

91 95

Scheme 23

THF, 0 °C

H P Mes* TMS TMS 96

679

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal H

TMS TMS TMS P N

Me2S=CH2 Mes*

TMS TMS TMS

THF, –40 °C

H

TMS

TMS

P

P N Mes*

97

TMS

N Mes* 99

98

Scheme 24

Two convenient routes for the preparation of P-halo-bis[bis(trimethylsilyl)methylene]phosphoranes 102–104 have been reported <1997S1013>. The reaction of phosphaalkene 100 with 1 equiv. of I2 resulted in a quantitative yield of the P-iodo derivative 104, which on treatment with AgCl gave P-chloro-bis(methylene)phosphorane 102. In a second synthetic route, phosphaalkene 101 undergoes a fast rearrangement to the compound 102 when traces of 4-dimethylaminopyridine (DMAP) are present. Reactions of 102 with a little molar excess of bromo- or iodotrimethylsilane readily lead to bromo- and iodo-substituted compounds in truly excellent yields after work-up (Scheme 25). TMS

TMS P

TMS

TMS TMS TMS

I2

TMS

THF, –78 °C 100%

TMS

P I TMS

100

104

AgCl

TMS–I

TMS

TMS P TMS Cl

TMS

DMAP (cat.)

P Cl

TMS TMS

TMS

TMS TMS–Br 100%

TMS P Br TMS

TMS 101

TMS 103

102

Scheme 25

The iminophosphine 97 reacts with iodine to form the methylene(imino)phosphorane 105. Upon subsequent treatment with AgCl, the corresponding chloro derivative 106 is obtained. Chlorine/bromine exchange in 106 with bromotrimethylsilane affords the bromo analog 107 (Scheme 26) <1998EJI83>. TMS TMS TMS I2 P N Mes* THF, –40 °C 97

TMS

TMS TMS P I

AgCl

TMS P Cl

Mes* N

Mes* N

105

106

TMS TMS–Br THF, rt

TMS P Br Mes* N 107

Scheme 26

(iii) Derivatization via phosphoranylidene carbenoids As mentioned in the previous section, phosphoranylidene carbenoids of the type Hal(Li)C¼P(¼Z)Y themselves represent valuable starting point for the synthesis of functionalized 35-methylenephosphoranes. They exhibit a pronounced carbanion character and remarkable stability even at elevated temperatures (10 C) due to the incorporation of the carbenoidic carbon atom into a heteroallylic -system <1999JA5953, 2002OM4919>. Thus, in typical carbanion fashion, the phosphoranylidene carbenoid 90 reacted with chlorotrimethylsilane to afford the silylated species Cl(TMS)C¼P(¼NMes*)Mes* <1994AG(E)982>. An analogous reaction with formation of a protonated species was observed when Br(Li)C¼P[¼C(TMS)2]Mes* was treated with water <2002OM4919>.

680

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

The stable LiF-carbenoid 108 was accessible by treatment of the mixed halogenated bis(methylene)phosphorane 94 with n-butyllithium. Metallation of the chlorofluoromethylene moiety proceeded exclusively via Li/Cl exchange. Treatment of the carbenoid 108 with chlorotrimethylsilane at 78 C afforded the silyl-substituted bis(methylene)phosphorane 109 (Scheme 27) <2002OM4919>.

TMS TMS P Mes* F

TMS

TMS BunLi THF, –78 °C

TMS

TMS-Cl

TMS P Mes*

P Mes* 96%

F

Cl

F TMS

Li(THF)3

94

109

108

Scheme 27

A synthetically valuable dilithiated species is assumed to be the intermediate in the reaction of 93 with 2 equiv. of n-butyllithium. It allowed the synthesis of disubstituted bis(methylene)phosphoranes 95 and 110 that again represent interesting synthons (Scheme 28) <2002OM4919>. TMS 2BunLi

TMS P Mes* Br Br

THF, –78 °C

TMS

TMS

TMS

Li

P Mes*

2RX

TMS P Mes* R

Li

R 95, R = H

93

110, R = Me

Scheme 28

6.22.1.4

Tetracoordinate Phosphorus Derivatives

The survey covers all types of isolable C,C-diheteroatom-substituted phosphorus ylides having a formal structure X1X2C¼PY3. For a treatment of materials published prior to 1994, readers are referred to chapter 6.22.1.4 in <1995COFGT(6)677>. This topic also forms the subject of two reviews <1996T1855, 1997RCR225> and a recent monography . There are four general methods for the production of the title compounds: (i) the direct introduction of a methylene moiety (X1X2C) into tervalent phosphorus compounds (PY3); (ii) the synthesis via the dehydrohalogenation or dehalogenation of corresponding phosphonium salts; (iii) the oxidative ylidation of tertiary phosphines containing a mobile hydrogen atom at the -carbon atom and behaving as CH acids; and (iv) the synthesis via a 1,2(C ! P) halogenotropic shift. Other methods for the synthesis of C-heterosubstituted phosphorus ylides are mainly restricted to examples including substitution reactions at the ylidic carbon atom.

6.22.1.4.1

Dihalosubstituted ylides, Hal2C¼PY3

The reaction of a halocarbene or carbenoid with a tertiary phosphine remains one of the most important methods for the preparation of phosphorus ylides bearing two halogen atoms at the ylidic carbon. Thus, the C,C-diidomethylenephosphorane 111 has recently been successfully generated from iodoform, triphenylphosphine, and ButOK. The ylide 111 can then undergo the Wittig reactions in situ (Scheme 29) <1999TL8579>. Interestingly, however, the alkenes 112 could not be obtained when ylide 111 was generated from CI4 and Ph3P <1985CC296>. It was recognized that the 1,2(C ! P) chlorotropic rearrangement might make available ylides containing a dihalomethylene group. Thus, trichloromethylphosphine Cl3C–P(NMe2)2 can be converted into the P-chloro ylide Cl2C¼P(Cl) (NMe2)2 by boiling in dichloromethane <1996T1855>. Recently study of the chlorotropy of phosphine systems was extended to Cl3C–PCl2, which may potentially undergo chlorotropic conversion to Cl2C¼PCl3. However, 35Cl NQR spectroscopy and

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

681

MP2/RHF/6-31++ G(d,p) calculations indicate that the latter is thermodynamically less stable than the corresponding phosphine. According to the opinion of the authors, special experimental conditions would be required to observe such conversion <2001MI163>. ButOK HCI3

+

I

Ph3P

PPh3

THF, rt

I 111

R = Alk, Ar

RCHO

I

THF, –78 °C

I

R

80%

112

Scheme 29

6.22.1.4.2

Oxygen-, sulfur-, and selenium-substituted ylides, RE(X)C¼PY3 (E = O, S, or Se)

The development of phosphonium ylides bearing oxygen substituents at the -carbon atom has proceeded at a slow pace. This slow growth may have been due to the low thermal stability of these species. Ab initio quantum chemical investigations show that the presence of an oxygen atom at the ylidic carbon atom stabilizes singlet carbenes but not ylides. Therefore, oxygensubstituted methylenephosphoranes have an enhanced tendency to dissociate into carbenes and tertiary phosphines <1986CB1331>. A new example of sulfur-substituted phosphonium ylides includes the compounds 114 and 115. The former has been isolated from the reaction of bis(diphenylphosphino)methane with hexafluorothioacetone dimer (HFTA) (Scheme 30). The first step of the reaction gives unstable carbodiphosphorane 113 which decomposes at temperatures higher than 70 C with the formation of a complex mixture of products. However, when an excess of HFTA was used, only the sulfur-substituted ylide 114 was formed <2001EJI2377>. Synthesis of the ylide 115, bearing thioether and phosphoryl groups at the carbon atom has been accomplished by thiophilic reaction of ethyldiphenylphosphinite with phosphonodithioformate (Equation (21)) <1994PS(86)169>. F3C

F3C [(F3C)2C=S]2 Ph2P

PPh2

Et2O, –70 °C

Ph F3C Ph P C P Ph CF3 S Ph CF3 S

[(F3C)2C=S]2 50%

S F3C Ph P

113

Ph P Ph CF3 S CF3 Ph 114

Scheme 30

S MeS EtO P O EtO

+

Ph 2 P OEt Ph

THF, 2 h, rt

Ph MeS EtO P Ph EtO P OEt O

+

EtO Ph P S Ph

ð21Þ

115

6.22.1.4.3

Nitrogen-, phosphorus-, arsenic-, and antimony-substituted ylides, R2E(X)C¼PY3 (E = N, P, As, or Sb)

Ab initio quantum chemical calculations carried out by Bestmann and co-workers <1986CB1331> predict instability for aminomethylenephosphoranes with respect to dissociation to a phosphine and a singlet carbene. Not surprisingly, efforts to obtain ylides of the type (R2N)2C¼PY3 were unsuccessful <1996T1855>. C-Amino-substituted phosphonium ylides are accessible only when anion-stabilizing substituent (X) at the ylide carbon atom compensate for the retarding influence of the nitrogen atom or when the latter is a part of aromatic or conjugated system. Thus, the stable phosphoniotriazaphospholide 116 and several related cyclic products were prepared from the products of the condensation of (TMS)2C¼PPh3 with PCl3 which serve as synthetic equivalents of a phosphoniophosphaethyne cation [Ph3P–CP]+. For instance,

682

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

cycloaddition reactions of [Ph3P–CP]+X (X = AlCl4, GaCl4 or TfO) with phenyl azide leads to the zwitterionic phosphoniotriazaphospholide 116 and to the phosphoniotriazaphospholes 117. The former readily undergoes a cycloreversion yielding Ph3PCN2 as intermediate. Its cycloaddition affords the remarkably stable diphosphoniodiazaphospholide chloride 118 as the final product <1997CB89>. N N N N

N N Ph N P

PPh3

116

N N

X– + PPh3

Ph3P

P

117

Cl– + PPh3

118

Nitrilimine 119 has been used in the synthesis of the stable phosphorus ylide 120. Formally, this method includes a coupling reaction between Me3P and the carbenic form of the dipole 119 (Equation (22)) <1997JOC292>. R

Me P C N N P R R R S –

+

+

Me3P

CF3SO–3

R 75% R

119 R = Pr2i N

Me + R P R N N P P Me S Me Me

–

CF3SO3

ð22Þ

120

The preparative chemistry of the highly reactive ylides bearing functionalized phosphorus substituents at the ylidic carbon atom, and that of related cyclic compounds, has continued to be an active area. Following earlier studies of the generation of phosphorus-substituted ylides by the condensation of silyl ylides with chlorophosphines, chloroarsines, and chlorostibines, it has been shown that reaction of silicon-substituted ylides with phosphorus trihalides gives rise to C-halophosphinyl ylides. Thus, the convenient procedure for the synthesis of ylides 121 and 122 involves the condensation of trimethylsilyl ylides R(TMS)C¼PPh3 with PCl3. The ylide 121 resulting from (TMS)2C¼PPh3 can react with a second mole of PCl3 to give 122 (Equation (23)). Interestingly, the bis(phosphinyl) ylides (Ph2P)2C¼PPh3, (ClPhP)2C¼PPh3 and (Cl2P)2C¼PPh3 (X-ray data reported) have analogous molecular structures. Details reflect the different charge transfer from the ylide center to the phosphinyl substituents <1999ZN(B)1>. It may be also noted in passing that ylide 121 readily undergoes reduction with LiAlH4 to give the H2P-functionalized ylide H2P(TMS)C¼PPh3 <1998EJI381>. R

R PPh3

TMS

+

PCl3

PPh3 –TMS–Cl

Cl2P

ð23Þ

121, R = TMS 122, R = PCl2

The trimethylsilyl ylide (TMS)2C¼PPh3 reacts smoothly with 2 equiv. of AsCl3 to give the bis(dichloroarsinyl)methylenephosphoranes 124. If 1 equiv. of AsCl3 is used, the substitution reaction stops at the dichloroarsinyl ylide 123, which slowly loses a further molecule of chlorotrimethylsilane leading to the cyclic ylide 125. For a structural proof 125 was converted to its bis(diphenylphosphinyl) derivative 126. If performed in pyridine, the reaction of equimolar amounts of (TMS)2C¼PPh3 and AsCl3 leads to a tetramer 127 (Scheme 31) <2000CEJ3531>. Likewise, 2,4-diphosphoranediyl-1,3-diphosphetanes are obtained from (TMS)2C¼PPh3 and PCl3 or PBr3 <1997CB1519>. The versatility of the substitution reactions is also demonstrated by the synthesis of highly functionalized ylide 128. It subsequently gets involved in an intramolecular reaction between the remaining PCl2 group and the phenyl ring to give the cyclic ylide 129. Other C-(dichlorophosphinyl) ylides, e.g., 130, have been obtained by the carbodiphosphorane route (Scheme 32) <1997JOM(529)87, 1996ZN(B)773, 1995CB379>.

683

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal TMS

Cl2As

AsCl3 PPh3

C6H6, rt

TMS

Cl2As

AsCl3

PPh3

PPh3

86%

TMS

Cl2As

123

AsCl3/Py

As As

Ph3P Cl

–TMS–Cl

PPh3

Cl

124

PPh3

Ph3P

As

As PPh3 Cl +

i. HCl

Cl As –

AsCl4

PPh3

As Cl

Cl As

ii. 2Ph2P(TMS)

Ph3P

H

As Cl

Cl–

126

125

127

+

PPh3

Scheme 31

Cl2P

TMS

Cl2P PPh3

PPh3

+

Cl2P

–TMS–Cl

Ph

Ph

Ph3P

122

P Cl 128

Ph3P=C=PPh3

–HCl

+

Cl2P Ph3P

PPh3

PPh3 P Cl

Cl–

Cl

PPh3 Ph3P

130

P

Cl– + PPh3

P 129

Scheme 32

Ylides 131 (R = Ph, 3-MeC6H4) react with 122 both at their 1- and ortho-position to yield the diphosphatetralines 132. The two P–Cl functions in the molecules 132 differ decisively in their spontaneous dissociation in a polar medium, and in their oxidation by elemental sulfur. With GaCl3 dicationic 1,3-diphosphanaphthalenes 133 are formed, which represent a novel 10 system (Scheme 33) <1996ZN(B)773>. Finally, the ylidediyl halophosphine oligomers, (XPCPPh3)n (X = Cl, Br, n = 2–4), were prepared from (TMS)2C¼PPh3 via (X2P)(TMS)C¼PPh3 and (X2P)2C¼PPh3 <1995AG(E)1853>. +

PPh3 R

R1

Cl2P PPh3 +

TMS

PPh3 Cl2P

131

–TMS–Cl –HCl

122

P R2

P Cl

PPh3 Cl

P

PPh3

132

131: R = Ph (a), 3-MeC6H4 (b) 132, 133: R1 = R2 = H; R1 = H, R2 = Me or R1 = Me, R2 = H

Scheme 33

2GaCl3

R1 P R2

133

2GaCl4– + PPh3

684

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

The condensation of dichlorophosphinyl-substituted ylides Cl2P(R)C¼PPh3 with (TMS)2S and (TMS)2Se has been used to effect the formation of the first stable monomeric phosphorus monochalcogenides 134. Ylides 134 are stabilized by a high contribution of the zwitterionic resonance forms, which follows both from the NMR and from an X-ray structure determination. Alkylation of 134 resulted in alkylchalcogeno(ylidyl)phosphenium salts 135 <1995CB1207>. The initial product of condensation of Cl2P(TMS)C¼PPh3 with (TMS)3P is a diphosphene 136, but, at ambient temperatures, dimerization to an ylide-substituted cyclotetraphosphine 137 occurs (Scheme 34) <1997CB1801>.

Cl2P PPh3

+

E P

(TMS)2E

PPh3 R

R

E P

MeX R = Et

X–

E P

PPh3

Me

Me

Et

X– PPh3 +

Et

135

134 R = TMS (TMS)3P

TMS

P P TMS

PPh3

1/2 Ph3P

TMS 136

TMS P P P P TMS

TMS PPh3

137 R = Alk, Ar, or TMS; E = S or Se; X = TfO, I, Br

Scheme 34

A carbene route has also received further study. Thus, the stable carbenes R2P(TMS)C have recently been used as reagents for the ylide synthesis. Instantaneous and quantitative formation of ylides 138 occurred when 1 equiv. of phosphine was added at 0 C to a solution of the carbene [(c-Hex)2N]2P(TMS)C] in pentane <1999AG(E)3727>. As a further development of this work the synthesis of phosphinyl ylides 139 has been achieved as shown in Scheme 35 <2002JA2506>. These same workers discovered that treatment of the stable [bis(diisopropylamino)phosphino](silyl)carbene with bis(diisopropylamino)phosphenium triflate leads to the formation of the adduct 140. The synthesis of ylide 141 was achieved by the reaction of 140 with methyl magnesium bromide (Scheme 36) <2000SCI(289)754>.

O R2P

Y3P

R2P

TMS

Pentane, 0 °C

TMS

PY3

O2

R2P PY3 TMS

138a–138e

R1R2PCl

TMS 2R1RP

R P R Cl

139a–139d 138: R = c-Hex2N; Y3P = Me3P (a), Et3P (b), Me2PhP (c), MePh2P (d), Ph3P (e) 139: R1R2 = –N(But)SiMe2N(But)– (a), R1 = R2 = But (b), R1 = Pr2i N, R2 = Ph (c), R1 = R2 = Ph (d)

Scheme 35

685

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

R2P

+ – CF3SO3

TMS

–

R2P+ CF3SO3 R P R

TMS

R2P

MeMgBr

R P R

TMS

140

R = Pr2i N

R P R Me 141

Scheme 36

The interaction of diphosphoryl-substituted ylide [Ph2P(O)]2C¼PPh3 (L) with phosphorus pentafluoride in acetonitrile has been studied in detail. The reaction gave chelated ylide cisPF4L+PF6 as shown by 19F and 31P NMR spectral data. Small amounts of linear adduct (PF5)2L were also observed <1997DOK(352)352>.

6.22.1.4.4

Silicon-, germanium-, and boron-substituted ylides, R3E(X)C¼PY3 (E = Si or Ge) and R2B(X)C¼PY3

There are few reports in the literature on the synthesis of silicon- and germanium-substituted phosphorus ylides via the dehydrohalogenation of corresponding phosphonium salts . These reactions generally proceed in high yields and tolerate the presence of a broad range of functional groups. The ability of phosphinomethanides [R2P–C(X)Y]Li+ to react with certain electrophiles via the phosphorus atom has been used for the preparation of new types of silyl ylides. As an example, PhSiCl3 reacts with 142 to give a fluxional, pentacoordinate silicon compound 143, which slowly rearranges to the tetraheteroatom substituted methane derivative 144 and further to the ylide 145 (Scheme 37). An analogous ylide (ButCl2Si) (TMS)C¼PMe2–PMe2 is obtained from ButSiCl3 and 142 instantaneously <1994ZN(B)1798>. Other reactions of lithium phosphinomethanides with polyfunctional chlorosilanes yield novel five- and six-membered heterocycles 146–150 with Si and P ring members .

PhSiCl3 + Li[C(PMe2)2(TMS)]

Me Me Cl P TMS Ph Si P Cl Me Me

–LiCl

142

Cl Ph Si Cl

144

143 TMS Cl Si Ph Cl

PMe2 PMe2 TMS

Me P PMe2 Me

145

Scheme 37

Me Me P P Me Me P PMe2 Me2P TMS TMS P Me TMS TMS P Me P P Me Me Me Me P

146

147

TMS

Me P Me TMS Me2P R Si PMe2 P Me 148

Ph Ph Si PMe2 Me2P Me2P

Si Ph

Ph

149

Ph Me TMS Si TMS TMS Me2Si PMe2

150

686

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

The reactions of ECl3 (E = P, As, Sb) with 3 equiv. of the phosphinomethanide 151 in all three cases leads to element–phosphorus bond formation and the first element–tris(P-ylide) derivatives 152–154 are obtained, along with some byproducts. For BiCl3, only the bisylide 155, besides elemental bismuth, is obtained. No Bi-containing compounds could be identified (Scheme 38) <1997JOM(529)151>.

ECl3 + 3LiC(PMe 2)(TMS)2 151

Me2P

E = P, As, Sb Et2O/ THF, –78 °C

(TMS)2C

E PMe 2 PMe2 C(TMS)2 C(TMS)2

152, E = P 153, E = As 154, E = Sb E = Bi

TMS

Et2O, –78 °C

TMS

Me Me P P Me Me

TMS

+

Bi

o

TMS

155

Scheme 38

The reaction of dichlorophosphines RPCl2 (R = Me, Ph, But, Cy2N) with 151 is dependent on the nature of R and leads, at least in part, to some unexpected products. As in the reactions of ECl3 (E = P, As, Sb), PP bond formation is also observed in the reaction of MePCl2 with 2 equiv. of 151. The bisylide 156 is obtained in good yield, but traces of 155 are also formed. If the steric demand of R in RPCl2 is increased, i.e., by reacting PhPCl2 with 151, in addition to 155 and 157, a new coupling product, the diphosphine bridged bisylide 158, is formed (Scheme 39). With further increase in the steric demand of R, i.e., with ButPCl2, only (ButP)3 and (ButP)4 were obtained. An analogous result is observed in the reaction of ButPCl2 with LiC(PMe2)2(TMS) <1997JOM(529)151>. Among the C,C-diheterosubstituted phosphonium ylides the only well-characterized boronsubstituted ylide is (MeO)2B(TMS)C¼P(NR2)2OMe prepared by the reaction of a stable carbene with B(OMe)3 <1994AG(E)578>.

MePCl2 Et2O, –78 °C

Me Me P TMS P P TMS Me Me TMS TMS Me

156 2LiC(PMe2)(TMS)2 151 PhPCl2 Et2O, –78 °C

Me

Ph P

Me TMS P P TMS Me Me TMS TMS 157

TMS +

TMS

Me Ph P P Me TMS Me P P Ph Me TMS 158

Scheme 39

6.22.1.4.5

Metal-substituted ylides, LnM(X)C¼PY3

Compared with the rich chemistry of transition metal ylide complexes, metallated phosphorus ylides, which formally arise from substitution of a hydrogen atom at the ylidic carbon by a metal atom and feature a dicarbanion center, have been investigated only briefly <1996T1855, 1994CRV1299>. Recently, reaction of the stable phosphinyl(silyl)carbenes with organolithium compounds was proposed as a new route to the -(lithiomethylene)phosphoranes <1999AG(E)678>. Indeed, addition of 1 equiv. of n-butyllithium to a solution of carbene R2P(TMS)C in pentane at

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

687

78 C instantaneously and quantitatively led to the desired ylide 159. Metallated ylide 159 is highly moisture sensitive and is easily transformed into the ylide TMS(H)C¼PR2Bun. It also reacts with electrophiles such as MeI and Ph2PCl to give the corresponding ylides 160 and 161, respectively (Scheme 40).

TMS R 2P

BunLi Pentane, –78 °C

TMS Li

Bun P R R

MeI or Ph2PCl

TMS

>92%

159 R = c-Hex2N

R1

Bun P R R

160, R1 = Me 161, R1 = Ph2P

Scheme 40

The gallyl-substituted ylide Me2Ga(TMS)C¼P(NR2)2Me is also accessible by reaction of a stable phosphinyl(silyl)carbene with GaMe3 <1994AG(E)578>.

6.22.1.5

Tetracoordinate Arsenic, Antimony, and Bismuth Derivatives

In comparison with C,C-diheterosubstituted phosphonium ylides (X1X2C¼PY3), the area of respective arsenic, antimony, and bismuth derivatives is poorly explored . This may have been due to the lack of general methodology for the synthesis of suitable precursors and in part to the low thermal stability of compounds bearing a formal EV¼C double bond (E = As, Sb, Bi). The difference between phosphonium ylides and their heavier analogs is commonly ascribed to the less efficient overlap between the sp2-C orbitals and the larger and more diffuse 4d orbitals of arsenic, stibium, and bismuth. Therefore, contribution of the ‘‘covalent’’ canonical form should become smaller as compared with the corresponding phosphonium ylides. Arsonium, and especially stibonium and bismuthonium ylides, are commonly less stable than their phosphorus counterparts and have a tendency to decompose both in solution and in solid state unless there is electronic stabilization. A significant increase in stability of the ylides X1X2C¼EY3, is observed, however, if electron withdrawing groups (X) such as carbonyl or sulfonyl are conjugated with the ylidic carbon atom <1998JOM(557)37, 1996BCJ2673>. The methods available for the synthesis of arsonium, stibonium, and bismuthonium ylides are nearly all analogous to methods used for the corresponding phosphonium ylides.

6.22.1.5.1

C,C-Diheterosubstituted arsonium ylides, X2C¼AsY3

Bis(sulfonyl)methylenetriphenylarsoranes, (RO2S)2C¼PPh3, remain only one type of well-characterized and studied C,C-diheteroatom-substituted arsonium ylides. No information about synthesis of other C,C-diheterosubstituted species is available since the publication of chapter 6.22.1.5.1 in COFGT (1995) <1995COFGT(6)677>.

6.22.1.5.2

Stibonium and bismuthonium ylides bearing heterosubstituents, X2C¼EY3 (E = Sb or Bi)

Yagupolskii and co-workers have described synthesis of a new bis(trifluoromethylsulfonyl)substituted stibonium ylide <1994ZOB1277>. Treating Br2C(SO2CF3)2 with 3 equiv. of tributylstibine results in the formation of stable stibonium ylide 162 (Equation (24)). The same group has also shown that treatment of sodium derivatives of the corresponding bis(sulfonyl)methanes with Ph3BiCl2 gives rise to the bismuthonium ylides 163 (Equation (25)). From the NMR spectra, zwitterionic canonical structures containing Bi+–C or Bi+–C¼S–O units may be assumed <1994JFC75>.

688

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal CF3O2S CF3O2S

CF3O2S

Br + Br

3Bu3n Sb

50%

+ – X SbBu3n

CF3O2S

ð24Þ

162 RfO2S RfO2S

Na

RfO2S

Br

+

Ph3BiCl2

– + X BiPh3

>90%

ð25Þ

RfO2S 163 Rf = F3C, n-C4F9, OCH2CF2CF2H

The synthesis, characterization, and solid-state structure are described for a reversed ylide 164, derived from 1,3-dimesityl-4,5-dichloroimidazol-2-ylidene and tris(trifluoromethyl)antimony (Equation (26)) <1999ZAAC(625)1813>. According to X-ray data, the ylide 164 retains reactantlike geometries for both the component fragments and is thus predisposed to facile cleavage of the carbene–antimony bond. Variable temperature solution NMR spectroscopic studies suggest that the carbene fragment readily dissociates from antimony center at temperatures as low as 95 C. Cl

Mes N

Cl

N Mes

Cl +

(F3C)3Sb 92%

Cl

Mes N – + X Sb(CF3)3 N Mes

ð26Þ

164

6.22.2

FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID

6.22.2.1

Tricoordinate Silicon and Germanium Derivatives

Progress over the past decade in the chemistry of p–p systems involving carbon and the heavier group 14 elements (Si, Ge) has been reviewed <1996MI71, B-1996MI367, B-1998MI857, 1998CCR565, 1999MI113>. The most readily available reaction pathways used to produce C,C-diheterosubstituted sila- and germaethenes are: (i) 1,2-elimination of a salt (LiY) from -lithiated silanes or germanes R2E(Y)–C(Li)R2 carrying a good leaving group (Y) on the element atom, (ii) 1,2-(SiC) silyl carbene–silaethene rearrangement, and (iii) coupling between a silylene or germanium(II) derivative and a nucleophilic carbene.

6.22.2.1.1

Diheterosubstituted silaethenes, X2C¼SiY2

Full details have appeared of studies of the formation, detection, and stabilization of the shortlived silaethene 167 <2000JOM(598)292, 2000JOM(598)304>. This compound is formed by reaction of trisilylmethanes 165 with alkali metal organyls or silyls via intermediates 166 and, in the absence of trapping agents, reacts with 166 to give the compounds 168, which in turn eliminate MX under formation of the 1,3-disilacyclobutane 169. In the presence of an excess of organyl or silyl azides, which act as very active trapping reagents for the silaethene, the [3+2]cycloadducts 170 are formed (Scheme 41). Direct detection of the silaethene 167 has been accomplished by laser-flash photolysis of Me3SiMe2SiC(N2)SiMe3 <2001OM5707>. Bromotrisilylmethanes 171–173 have been used as sources of the corresponding isomeric silaethenes with six Me and two Ph substituents. Phenyllithium converts the above compounds by Br/Li-exchange to lithium organyls, which in ether solution are in equilibrium with unsaturated silicon derivatives. The intermediacy of the silaethenes has been established by their trapping with 2,3-dimethylbutadiene <1996JOM(524)147>.

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Me

TMS TMS Br

RM

Si Me –RBr

X

Me

TMS TMS M

Si Me X

166

165

–MX TMS TMS M

689

Me TMS Me

166

+MX Me

TMS Si

Si

Si Me TMS X Me

TMS

168

Me 167

R1N3 TMS Me2Si TMS SiMe2 TMS TMS

TMS

TMS SiMe2 N N R1 N 169

170

RM = BunLi, PhLi, (TMS)2CHLi, Bu3t SiNa; X = F, Br, PhO

Scheme 41

R R1 Br

Ph Si Me Br 171

R R2 Br

Me Si Me Br 172

Me R1 Si Me R1 Br Br 173

R = TMS, R1 = PhMe2Si, R2 = Ph2MeSi

Dehalogenation of the sterically overloaded trisilylmethanes R*(TMS)BrC–Si(X)Me2 has been exploited for the synthesis of silaethene R*(TMS)C¼SiMe2 (R* = But3Si). Reaction of R*(TMS)BrC–Si(X)Me2 (X = F, TfO) with PhLi leads to R*(TMS)LiC–Si(Ph)Me2, while R*(TMS)BrC–Si(F)Me2 reacts with But3SiNa to give R*(TMS)NaC–Si(F)Me2. The latter compound transforms in THF in the presence of Me3SiCl into the corresponding silaethene, which may be trapped by reactants like MeOH, Me2CO, or 2,3-dimethylbutadiene. It follows from this study that the metastability of compounds (ButnMe3n Si) (TMS)C¼SiMe2 with an increasing number of But groups pass through a maximum for n = 2 <1997JOM(531)47, 1996CB471>. Using a new synthetic pathway, Oehme and co-workers recently succeeded in preparing a variety of new C,C-disilyl-substituted silaethenes. They observed that dichloromethyltris(trimethylsilyl)silane reacted with an excess of organolithium reagents RLi (R = Me, Bun, Ph) under substitution of the two chlorine atoms and a complete reorganization of the whole substitution pattern of the molecule to produce silanes of the type (TMS)2CH–Si(TMS)R2 <1999OM1815>. As shown in Scheme 42, in this process the transient silaethenes 174 and 175 occur as intermediates, which are trapped by the organolithium reagent present in the reaction mixture, and the reaction affords 176 as the end product after aqueous workup. However, if, for the reaction with Cl2CHSi(TMS)3, an organolithium reagent is chosen with a group R, which, when introduced at the silicon atom, provides sufficient stabilization of a silaethene system through an intramolecular donor–acceptor interaction, it possible to halt the reaction at this stage and to isolate a silaethene. This was achieved, for example, in the reactions of Cl2CHSi(TMS)3 with suitably functionalized organolithium compounds in the molar ratio 1:2,

690

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

which led to the isolation of intramolecularly donor-stabilized silaethenes 177–179 <2000AG(E)1610, 2001JOM(621)261, 2001CEJ987>. By the use of sterically congested organolithium derivatives, the nucleophilic addition of RLi to the C¼Si bond can also be prevented and kinetically stabilized silaethenes obtained. Thus, silaethene 180 was synthesized by the reaction of Cl2CHSi(TMS)2Ph with 2,4,6-triisopropylphenyllithium. Similarly, silaethenes 181 and 182 were prepared from Cl2CHSi(TMS)3 and 2,4,6-triisopropylphenyllithium or 2-t-butyl-4,5,6-trimethylphenyllithium (Scheme 43) <2001EJI481>.

Cl

TMS

Cl

–RH

TMS

TMS Si TMS

Cl Li Cl

RLi

Si TMS

TMS Si TMS

–LiCl

Cl

TMS

TMS

TMS

TMS Si

Cl

TMS 174

RLi

Cl Li TMS

R Si TMS TMS

for RLi = MeLi, BuLi, PhLi –LiCl

for RLi = Li–D –LiCl

TMS

TMS TMS

D

TMS

Si

Si

R

TMS

175

TMS

i. RLi ii. H2O TMS

TMS

Si R TMS

R 176

Scheme 42

Me2N TMS

Me2N TMS Si

TMS

Si TMS

177

Me2N TMS

TMS

TMS 178

NMe2 Si

TMS

TMS 179

Ottosson and co-workers <2002OL1915> have used Brook’s procedure to generate transient silaethenes R2N(TMS-O)C¼Si(TMS)2 (R = Me, Ph). Formation of the latter through photolysis of the compound Me2NC(O)Si(TMS)3 was attempted before and found to be unsuccessful since no reaction occurred upon long irradiation <1991JOM(403)293>. In a modification of this

691

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

method, the silaethenes have been prepared by thermolysis of the silylamides R2NC(O)– Si(TMS)3. The short-lived silaethenes are trapped with 2,3-dimethylbutadiene to quantitatively yield only one of the possible diastereomers of the cyclic allylsilanes. Ab initio calculations reveal that the silaethene Me2N(TMS-O)C¼Si(TMS)2 is characterized by reversed C+–Si bond polarization and features a carbon–silicon single bond and a pyramidal silicon atom.

Cl

TMS

TMS

TMS

R2Li

Si

Si TMS Cl

R1

–R2Cl, –LiCl

Cl

R2

TMS Li Cl

R2Li

R1

TMS

Si TMS R1

R2

TMS –LiCl

Si TMS

R1

TMS Si

TMS

Si TMS

1

R 180, R1 = Ph

TMS 182

181, R1 = TMS

Scheme 43

Related carbene–silylene adduct 183 in which the CSi bond is best formulated as being electrostatic in nature, with the carbene moiety as electron donor and the Si(NN) fragment as acceptor, has been prepared according to Scheme 44. The compound 183 is monomeric, with the three-coordinate C and Si atoms in an almost planar (C) or pyramidal (Si) environment <1999CC755, 2000JCS(D)3094>.

R NH NH R

Cl2CS

R N S N R

C8K

R N Si N R

R N N R

Pentane, –25 °C 83%

R R N – N + Si N N R R 183

Scheme 44

6.22.2.1.2

C,C-Diheterosubstituted germaethenes, X2C¼GeY2

The C¼Ge bond is of low intrinsic thermodynamic stability, so that stable germaethene derivatives all contain sterically bulky substituents at both germanium and carbon <1998CCR565>. Uncomplicated germaethenes exists only as transient species. The methods available for their synthesis are nearly all analogous to methods used for the corresponding silaethenes <2000JOM(598)292, 2000JOM(598)304>. The most established process for the generation of transient C,C-diheterosubstituted germaethenes is based on the formation of the C¼Ge bond by the salt elimination method. For example, germaethene (TMS)2C¼GeMe2 is formed as a short-lived intermediate by reaction of (TMS)2BrC–GeMe2X with RLi via (TMS)2LiC–GeMe2X (X = electronegative substituent, R = organyl) <2000JOM(598)304>. Interestingly, thermolysis of 184 at 100 C in the presence of propene, butadiene, 2,3-dimethylbutadiene or isobutene leads to ene reaction product and/or [4+2]-cycloadducts of the germaethene 186. The formation of these trapping products proves the intermediate existence of a compound with Ge¼C bond and indicates that the equilibrium between 185 and 186 lies at the side of germaethene (Scheme 45) <1996JOM(511)239, 1996JOM(519)107>.

692

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Me3Ge Me3Ge Li

But Si But F

100 °C

Me3Ge

But

–LiF

Me3Ge

But

184

Me

185

Me

GeMe3

Me Ge

80%

SiMeBut2

GeMe3 Me

Ge Me

SiMeBu2t

77%

Me GeMe3 Ge SiMeBu2t

186

Scheme 45

Recently, the [4+2]-cycloadduct of (TMS)2C¼GeMe2 and anthracene has been proposed as a ‘‘store’’ for the germaethene <2000CJC1412>. Adduct 188 can be prepared by reaction of an excess of anthracene in benzene with germaethene precursor 187. Above 100 C it decomposes reversibly via thermal cycloreversion into (TMS)2C¼GeMe2 and comparatively unreactive anthracene. The half-life of the anthracene adduct in the presence of 2,3-dimethylbutadiene (DMB) in t-butylbenzene on thermolysis at 130 C is found to be 12 h. In the absence of DMB, thermolysis leads to the dimer of the germaethene (Scheme 46). TMS TMS Li

Me Ge Me OPh

100 °C

TMS

Me Ge

–PhOLi

TMS

Me

187

TMS

TMS GeMe2

188 t-BuC6H5 130 °C Me TMS Me Ge TMS

TMS Me2Ge TMS GeMe2 TMS TMS

Scheme 46

Among the stable C,C-diheterosubstituted germaethenes the only well-characterized and studied compounds are adducts obtained from the germylenes and the free carbenes. New examples are the germaethenes 189 and 190 prepared by reactions between the appropriate germanium(II) compounds and nucleophilic carbenes <1993IC1541, 2000JCS(D)3094>. Related carbene–germylene complex 191, in which the ring represents a diborylcarbene system, is also readily available from its factors, the kinetically stable diarylgermylene and Berndt’s carbene <1999HAC554>. It should be made clear that the structures of 189 and 190 are best described as a Lewis base–Lewis acid adducts in which the newly formed CGe bond is not a true double bond but rather highly polarized C+Ge bond. In contrast, the X-ray structure analysis as well as NMR data of cryptodiborylcarbene adducts 191 suggest some significance for the ylide resonance formula of type CGe+, expected from the interaction between an electrophilic carbene and a nucleophilic germylene <1987AG(E)798, 1999HAC554>.

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Mes N – + Ge I N I Mes

R R N – N + Ge N N RR

189

But B

TMS TMS

190, R = ButCH2

693

B But

Ge RR

191, R = 2-But-4,5,6-Me3C6H

Phosphino(silyl)carbene 192 reacts with germylenes affording the C-germylphosphaalkenes 194 (Scheme 47). It is reasonable to postulate the primary formation of the germaethenes 193, which would undergo a subsequent 1,3-shift of Me2N group from phosphorus to germanium atom to produce compounds 194. The instability of 194 is not surprising whatever the polarity of the C¼Ge bond, since the phosphorus center is not efficient enough to stabilize an adjacent positive charge and destabilizes a negative charge <1992IC3493>. Tmp

Tmp Me2N P

Me2N P +

GeR2

TMS

THF, rt

192

TMS

R Ge R

Tmp P 47–68%

R Ge NMe2 R

TMS

194

193

R = (TMS)2N or Mes*NH, Tmp = 2,2,6,6-tetramethylpiperidino, Mes* = 2,4,6-But3C6H2

Scheme 47

Okazaki and co-workers prepared the first stable germaketenedithioacetal 197 by treatment of overcrowded diarylgermene 195 with carbon disulfide. The formation of 197 can be reasonably interpreted in terms of the intermediacy of thiagermiranethione 196, as shown in Scheme 48. Exclusive formation of 197 without any 1:1 addition product, even in the presence of an excess amount of carbon disulfide, implies a much higher reactivity of the thiocarbonyl unit of 196 toward germylene 195 than that of carbon disulfide <1995CC1425, 1996CL695>. Tbt Tbt Ge Tip

CS2 THF, rt

Tbt

Tbt

– +

Ge

Ge S C S

S

Tip

Tip

Tip

Ge

195 S

S + –

S Ge

Tbt Tip

196

195

46%

S

Tbt Ge Tip

Tbt Ge S Tip

197 Tbt = 2,4,6-[(TMS)2CH]3C6H2, Tip = 2,4,6-Pr3i C6H2

Scheme 48

6.22.2.2

Functions Incorporating a Doubly Bonded Boron

Among organoboron compounds many C,C-disilyl-substituted doubly bonded molecules have now been synthesized, such as methyleneboranes 198, 2-borataallenes 199, and boriranylideneboranes 200. Stable methyleneboranes are obtained only when the C¼B double bond is sterically shielded by large substituents. In addition, electronic stabilization is necessary either through formally nonbonding electron pairs on the atoms directly adjacent to the dicoordinated boron atom or through electropositive substituents at the position to the dicoordinated boron atom.

694

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

Thus in amino-substituted methyleneboranes 198 (Y = R2N) or 2-borataallenes 199, the electron deficiency at the dicoordinated boron atom is relieved through – delocalization of the formally nonbonding electron pairs on the neighboring atom. In nonclassical methyleneboranes 200, the electron-deficient center at the dicoordinated boron atom forms nonclassical three-center, twoelectron (3c–2e) bonds with neighboring bonds. X X

X B Y

X

R

–

M+

B X

198

R B B R

X

R 199

200

There are a number of specialized methods for the formation of X2C¼B functions which, however, do not seem to have general applicability. For further details a comprehensive review on this subject should be consulted <1996MI355>.

6.22.2.2.1

Methyleneboranes, X2C¼B-Y

Various synthetic pathways for the formation of X2C¼BY species are outlined in Scheme 49 <1993AG(E)985>. The simplest route involves a 1,2-elimination reaction at organoboranes having functional substituents X at carbon and Z at boron atom which combine to a thermodynamically favored leaving molecule XZ, e.g., Me3SiF. This is currently the method of choice in the synthesis of C,C-disilyl-substituted methyleneboranes of the general formula (TMS)2C¼BY <1989CB1057>. Methods involving either the cleavage of BC single bonds in (borylmethylene)– boranes or reactions of borataalkynes with electrophiles have also proved sufficiently effective <1993AG(E)985, 1991AG(E)594>. Finally, the thermal cycloreversion of 1,3-diboretanes and 1,2-dihydroboretes is of considerable potential for the generation of methyleneboranes <1990AG(E)401>.

X X

Y

B

–

B X

B

TMS

Li+ C B

Z TMS

Cycloreversion (–TMS

Elimination (–XZ)

X B Y

X

TMS)

Reactions with electrophiles (+E+)

Cleavage of C–B bond

B Cl

Reductive elimination

Reductive cleavage

B B

–

–

B C B

2Li+

B Cl

Scheme 49

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

695

The organic chemistry of boriranylideneboranes 200, obtained by Berndt and co-workers <1993AG(E)985> in the early 1980s through reductive elimination and rearrangement of the diborylalkenes has been extensively studied and is characterized by cleavage of bonds in the threemembered ring and migration of substituents <1995AG(E)1111, 1997AG(E)1469>. These species seem to be valuable starting materials for the synthesis of new type of heterosubstituted methyleneboranes. Thus, the boriranylideneboranes 200a and 200b add B2Cl4 under cleavage of the Si2CB bond to yield the (borylmethylene)boranes 201 in which three boron atoms are bonded to a methylene carbon (Equation (27)) <2001EJI387>. Reaction of the t-butyl derivative 200c with [Co(Cp)(C2H4)2] provides the metalacycle 202 featuring the metal-substituted C¼B double bond (Equation 28) <1998CEJ44>. TMS

R

R B

B2Cl4 B R

TMS

Hexane, –85 °C 33–50%

200a, 200b

Cl

B B

Cl

B

TMS BCl2 TMS

R

ð27Þ

201 R = Dur (a), Mes (b)

TMS

But B

TMS

B But

[Co(Cp)(C2H4)2]

TMS

Hexane, reflux, 0.5 h

TMS

Co B B But

But

ð28Þ

200c 202

6.22.2.2.2

2-Borataallenes, [X2C¼B¼CY2]

Among possible synthetic strategies for 2-borataallenes, thermally induced isomerization of C-borylboriranide 203 prepared from 200a by reaction with phenyllithium <1992AG(E)1238> or 2-boryl-1,3-diboretanides 205 accessible from the reaction of 204 with t-butyllithium <1990AG(E)1030> play an important role. In the last case, authors suggest the 1-bora-3-boratabutadiene as an intermediate, whose transformation into 2-borataallene requires a 1,3-migration of an aryl group from the tri- to the dicoordinated boron atom. Reductive dimerization of the methyleneborane 198a has also been used in the synthesis of borataallenes (Scheme 50) <1990AG(E)1030>. The 1-boryl-2-borataallenes react with electrophiles to form the (borylmethylene)boranes <1993AG(E)985>.

6.22.3

FUNCTIONS INCORPORATING A DOUBLY BONDED METAL

For the purpose of this survey, the above functions will be defined as the species of the formula X1X2C¼MLn (X1, X2 = heteroatom substituents), which formally contain a double bond between carbon and metal. Until 1990s, apart from the well-studied transition metal–dihalocarbene complexes, there was comparatively little information on compounds involving C¼M bonding between three-coordinate diheterosubstituted carbon and metal <1995COFGT(6)677>. The situation has changed recently. A breakthrough was the isolation of the first free N-heterocyclic carbene (NHC) by Arduengo and co-workers <1991JA361>. Since then NHCs and related acyclic diaminocarbenes have become accessible as ‘‘bottle-able compounds’’ and their inorganic and organometallic chemistry has gained enormously in versality and depth <1997AG(E)2162>. Numerous new varieties of diheterosubstituted carbene complexes were reported within a short period of time. The reviews by Herrmann <2001MI1, 2002AG(E)1290>, Arduengo <1999ACR913>, Bourissou and co-workers <2000CRV39>, and Enders and Gielen <2001JOM(617/618)70> provide a valuable survey of the literature up to 2002. In comparison with transition metal–carbene complexes, the area of respective molecule with carbon–Main Group metal double bond remains rather poorly explored <1998CCR565, 2001MI621>.

696

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Dur B

TMS

TMS B Dur

PhLi

Ph

TMS –

TMS

B

TMS

∆

B

TMS

B Dur

Dur

Dur

Li+

200a

Ph B Dur Li+

203 1,2-Dur shift

TMS

–

B TMS

TMS B TMS

TMS

Li

Li+

TMS

–

0.5

B Dur Dur

TMS

Ph B Dur Li+

Dur

Dur –

B

–

TMS

TMS

2Li+

B TMS

198a

Ar B

TMS TMS

B Ar

B Ar

ButLi

TMS TMS

Ar But B – B B Ar Ar Li+

∆

TMS TMS

Ar B–

But

TMS

–

Ar B But

B

B Ar B Ar Li+

TMS Li+

B Ar Ar

Ar = Dur, Mes 205

204

Scheme 50

6.22.3.1 6.22.3.1.1

Transition Metal–Carbene Complexes N-Heterocyclic carbene complexes

The use of N-heterocyclic carbenes I–IV and related acyclic diaminocarbenes is a recent development in the synthesis of transition metal–carbene complexes (Figure 2) <2002AG(E)1290>. Experimental and theoretical studies have established that NHCs bind to the transition metal by -donation; back-donation from the metal is minimal, thus the electronic properties of diheterosubstituted singlet carbenes are comparable to trialkylphosphines. Typical procedures for the synthesis of NHC–transition metal complexes are: (i) free carbene route (deprotonation of the corresponding azolium salts with bases prior to metallation; (ii) direct metallation of the azolium salts with a basic metal precursor such as Pd(OAc)2 or [Ir(COD)(OEt)]2; (iii) reaction of the corresponding electron-rich alkenes (enetetramines) with mononuclear or bridged dinuclear organometallic compounds; (iv) metal exchange starting from silver carbenes (transmetallation); and (v) oxidative addition of a low-valent metal to a 2-chloro-1,3-disubstituted imidazolinium salt. R N

R N

R N

R

N R

N N R

I

II

( )n N

III

Figure 2 N-Heterocyclic carbenes.

R N S

IV

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

697

A new approach to the preparation of NHC–transition metal complexes was recently reported by Cloke and co-workers <1999OM3228>. It concerns the possibility of obtaining group 10 homoleptic carbene complexes via the co–condensation of nickel, palladium, or platinum vapor with 1,3-di-t-butylimidazol-2-ylidene. This route provides a straightforward synthesis of the stable, two-coordinate metal–carbene complexes 206–208, one compound of which 207, has been inaccessible to date by solution technique (Equation (29)). But

But But

N

N

Cocondense

2

+

M(at)

N

N M

–196 °C

N

N But But

But

ð29Þ

206, M = Ni 207, M = Pd 208, M = Pt

Another interesting example of the formation of transition metal–carbene complex from free NHC is the preparation of vanadium(V)–carbene adduct 209 in which the transition metal is in a high oxidation state (Equation (30)). In this case, complexation of an N-heterocyclic carbene to vanadium(V) results in an electrophilic singlet Ccarbene, which is typical of Fischer type systems, but is unusually supported by a high-oxidation-state metal center. Both solid samples and dichloromethane solutions of 209 are stable in air and showed no decomposition on standing for over two months <2003JA1128>. Mes

Mes

N

N +

N Mes

Cl3VO

Toluene, rt 76%

V(O)Cl3 N

ð30Þ

Mes 209

Erker and co-workers used three different stable imidazole-derived carbene ligands to prepare a series of trans-[(imidazolyl-2-ylidene)2MCl4 complexes of zirconium and hafnium <2002JOM(663)192>. Scheme 51 illustrates synthetic approaches to these species. Deprotonation of 1,3-diisopropylimidazolium chloride 210 with NaH–KOBut gave 1,3-diisopropylimidazol-2-ylidene 213 in 95% yield. Treatment of N-methylimidazole with 2-bromobutane yielded the imidazolium salt 211 which was converted to the stable carbene 214 by treatment with KH–KOBut. Finally, the imidazolium salt 212, prepared by N-alkylation of N-methylimidazole with bromomethyl-2,4,6trimethylbenzene, was converted to the unsymmetrically substituted Arduengo carbene 215 by treatment with NaH in THF. Reaction of the carbenes 213–215 with MCl4(THF)2 (M = Zr, Hf) affords the corresponding carbene–group 4 Metal halide complexes 216–219 as stable solids. The first carbene-linked cyclophane 221 was prepared by Youngs and co-workers from the bis(imidazolium) salt 220, which results from a straightforward alkylation reaction of 2,6-bis(imidazolemethyl)pyridine. Silver oxide was used to deprotonate 220 and, at the same time, to introduce the metal center (Scheme 52) <2001OM1276>. As a further development of the free carbene route the synthesis of N-borane-protected NHC complexes has been achieved as shown in Scheme 53. 1,10 -Bis(3-borane-4,5-dimethylimidazolyl)methane 222 was deprotonated to give a dianionic dicarbene compound 223. Its reaction with Cp2MCl2 (M = Ti, Zr) allowed the formation of the corresponding titanocene and zirconocene complexes 224 and 225 in 75–80% yields <2002EJI1607>. Metal acetates allow the synthesis of NHC complexes without isolation of free carbenes. This procedure combines the advantages of readily available starting materials with the in situ deprotonation of the azolium salts and avoids free carbenes or expensive organometallic precursors. For example, since the acidic methylene protons in bisimidazolium salts 226 are also attacked under common deprotonation conditions, a pathway via free biscarbenes leads to a complex mixture of products. However, palladium(II) acetate in wet DMSO deprotonates 226 to give bridged palladium–biscarbene complexes 227 in 85–90% yields <1999JOM(572)239, 2000CEJ1773>. The bisimidazolium salts 226 also undergo a selective deprotonation with sodium acetate/platinum(II) halide, and this has been used in a one-pot synthesis of novel platinum(II) biscarbene complexes 228 (Scheme 54) <2002JOM(660)121, 2003JOM(671)183>.

698

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal Cl–

N+

NaH/KOBut

N

MCl4(THF)2

N

THF, 95%

N

91–99%

N

H

MCl4

N

210

2

216, M = Zr

213

217, M = Hf Br–

N+

NaH/KOBut

N

ZrCl4(THF)2

N

THF, 65%

N

89%

N

H N

211

ZrCl4 2

218

214 Br–

N+

NaH

N

ZrCl4(THF)2

N

THF, 86%

N

94%

N

H N

ZrCl4

215

212

2

219

Scheme 51

2+ 2PF6–

N N

N H H

N

N +

Br

Br

N i, ii

N + N

N

H H N

N N + N

Ag2O DMSO 55 °C

2PF6–

N

N

N Ag

N Ag

N

N

N N

N 220 221

i. CH2Cl2, rt; ii. NH4PF6

Scheme 52

Interestingly, the pK’s of the bisimidazolium salts 226 should make one think that NEt3 is not strong enough to deprotonate the azolium center. Nevertheless the addition of an excess of the base (20:1), together with the rapid coordination of the carbene to metal, displays the equilibrium of deprotonation to the formation of the desired products. Thus the synthesis of complexes 229 and 230 includes the deprotonation of the bisimidazolium precursor with NEt3 in the presence of [RhCl(COD)2]. When the reaction is carried out in the presence of air, 229 is the major product obtained. Under inert conditions with degassed acetonitrile, complex 230 is mainly formed <2003IC2572>. A similar approach has been applied to the preparation of dirodium(I) bisimidazolium carbene complex 231 <2003OM440> and new ruthenium(II) CNC-pincer bis(carbene)complexes 232 and 233 (Scheme 55) <2003OM1110>.

699

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

N

2BH3.THF

N

THF, –78 °C 97%

N

N

N

N N BH3

N H3B 222

2– 2BuLi

N

THF, –78 °C

Cp2MCl2

N 2Li+

N BH3

N H3B

N

THF, –78 °C

N

N N M H3B Cp Cp BH3

223

224, M = Ti (75%) 225, M = Zr (80%)

Scheme 53

N 2

CH2X2

+

+

N

N

N

DMSO, rt

N R

N R

N R

Pd(OAc)2 or 2X– PtX , 2NaOAc 2

N

N N M X R R X

226

227, M = Pd 228, M = Pt

R = Me, Bun; X = Br, I

Scheme 54 [RhCl(COD)]2

N + N

N

NEt3 + KI + KPF6

+ 2I–

N

Rh

CH3CN

N

N

+ N

I

I

N

N or

Rh

N

N

N I Rh I MeCN NCMe 230

229

Scheme 55

Bun N

N

N Rh

N Br

Br

N Bun

N

Br N Ru N N Br CO Bun Bun N

Rh

232

231

2PF6–

C C N

Ru C C

N N 233

C

N N=

N Bun

N

N N Bun

+ PF6–

700

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

A further exploitation of the azolium route now covers metallocenes, such as 234. This synthesis is successful for both nickelocene and chromocene (Equation (31)) <1999OM529, 2000JOM(596)3>. Mes N

Cl–

Mes N

+

THF

M

+

Cl

–C5H6

N Mes

M

N

ð31Þ

Mes 234 M = Ni (70%), Cr (67%)

A recent paper has described an efficient entry into palladium complexes bearing NHC ligands on the basis of the oxidative addition Pd(PPh3)4 to the easily accessible 2-chloro-1,3-disubstituted imidazolium salt 235 <2003OM907>. This novel method promises a broad substrate scope and allows for substantial structural variations since the required 2-chloro-1,3-disubstituted imidazolium salts can be easily prepared from cyclic ureas or thioureas on treatment with, for instance, oxalyl chloride. Examples are depicted in Schemes 56 and 57. Interaction of the imidazolium salts 235 (X = PF6, BF4) with an equimolar amount of Pd(PPh3)4 in refluxing dichloromethane leads to the formation of cis-236 as the primary products, which isomerize with time to the more stable trans-236. Although the reactivity of chloride 235 (X = Cl) follows the same trend, giving rise to the expected cationic complex trans-236 in 87% yield, the equilibrium between the cationic and the neutral Pd–NHC complexes leads to small amounts of complex 237 in addition to 236. This propensity is more pronounced in case of the enantiomerically pure NHC complex 239, which is obtained as the only product on treatment of the chiral imidazolium salt 238 with Pd(PPh3)4 under similar conditions.

+ X–

N Cl N

Pd(PPh3)4

N

–2PPh3

N

Cl Pd PPh3 PPh3

+ X–

235 cis-236

N Ph3P

+ N

Cl Pd Cl PPh3

N X = Cl

237

N

PPh3 Pd Cl PPh3

+ X–

trans-236

X = PF6, BF4, Cl

Scheme 56

Complexes of NHC can also be generated starting from aminals. In particular, the successive treatment of [PdCl2(PEt3)2] with the aminal 240 leads to the formation of trans-mono- and transbis(carbene) complexes 241 and 242 containing the 1,3-diallylimidazolidin-2-ylidene ligand. If, in addition, [Pd2Cl4(PEt3)2] is employed, the cis-complexes 243 and 244 are obtained in high yields as the only organometallic products (Scheme 58) <2002OM5428>. Special NHC-transfer reagents are the silver(I) complexes <2002HAC534>. They are formed in a simple way by treatment of imidazolium salts with Ag2O and transfer their NHC ligands to other metals, for example, Pd, Pt, or Rh <2002JCS(D)2852, 2002TA1969, 2003JCS(D)699>. This technique overcomes the difficulties arising from the use of strong base to yield free heterocyclic carbenes and seems to be particularly effective in the case of functionalized NHCs. For example, Matsumoto and co-workers have demonstrated that the imidazolium chloride 245 reacts with an

701

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

Ag2O suspension in dichloromethane at a ratio of 1:1 to afford 246. Attempt to prepare the free carbene by deprotonation of the imidazolium salt 245 with either KOBut or KH was not successful probably due to the high acidity of the methylene protons linking phenyl and imidazole rings (Scheme 59) <2002JOM(654)233>. The silver-NHC complex 247 was prepared in a similar manner. It smoothly reacts with [PdCl2(COD)] to yield the corresponding palladium–carbene complex 248 <2002OM5204>.

[C(O)Cl]2

Cl2C=S 64%

NH HN

N

82%

N S

+ Pd(PPh3)4

Cl– N

–3PPh3

N

N

85%

Cl

N

Ph3P Pd Cl Cl

238 239

Scheme 57

R N NMe2

R N

PdCl2(PEt3)2 –PEt3, –Me2NH

N H R

N R

240

Cl Pd PPh3 Cl

R N

240 –PEt3, –Me2NH

N R

trans-241

R N

[PdCl2(PEt3)]2 –Me2NH

N R

PPh3 Pd Cl Cl

Cl Pd Cl

R N N R

trans-242

R RN N

240 –PEt3, –Me2NH

N R

cis-243

N R Pd Cl Cl

cis-244

R = CH2=CH-CH2

Scheme 58

2Cl– 2

N

N Me

+

Me N

60 °C, 2 h Cl

Cl

N

+

+

91% 245

Ag2O CH2Cl2, rt 95%

Me N

N

N

N Me Ag

Ag

Cl

Cl 246

Scheme 59

N

N Me

702

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal N N

N

N

N

O

O Ag Br

Cl Pd Cl

247

N

248

An entirely different approach for the generation of the metal–NHC complexes is based on the template-controlled formation of NH,O- and NH,NH-stabilized cyclic carbene ligands <1999CCR(182)175>. An example is outlined in Scheme 60. The 2,3-dihydro-1H-benzimidazol-2ylidene complexes 252 (M = Cr, W) have been produced by template-controlled generation of a carbene ligand from 2-azidophenyl isocyanide and [M(CO)5(THF)]. The polar Ph3P¼N function in complexes 249 can be hydrolyzed with H2O/HBr to afford the unstable 2-aminophenyl isocyanide species 250, which spontaneously cyclize by intramolecular nucleophilic attack of the primary amine at the isocyanide carbon to yield the complexes 251. Double deprotonation of the cyclic NH,NHcarbene ligand in 251 with KOBut and reaction with 2 equiv. of allyl bromide affords the N,N0 dialkylated benzannulated N-heterocyclic carbene complexes 252 <2003CEJ704>.

M(CO)5(THF) N3 N C

THF, rt 63–65%

N3 N C OC M CO OC CO CO

PPh3 THF, rt 75–80%

N PPh3 N C OC M CO OC CO CO 249

HBr/H2O

i. KOBut ii. C3H5Br N

N

OC M CO OC CO CO 252

65%

H N

N

H OC M CO OC CO CO

78–85%

251

NH2 N C OC M CO OC CO CO 250

M = Cr, W

Scheme 60

6.22.3.1.2

Silicon-substituted carbene complexes, R3Si(X)C¼MLn

The silyl(ethoxy)carbene complexes XPh2Si(EtO)C¼W(CO)5 253 and 256 were prepared by the Fischer route starting from W(CO)6 and LiSiPh2X followed by alkylation of the formed anionic acyl complex with [Et3O]BF4. For the synthesis of 256, an excess of [Et3O]BF4 has to be avoided, because otherwise the amino group is cleaved. Reaction of 253 with Me2NH and of 256 with MeNH2 resulted in the formation of the corresponding silyl(amino)carbene complexes 254 and 257 in high yields. When ether solutions of 254 or 257 were irradiated with UV light, CO was

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

703

evolved, and the thermally stable tetracarbonyl complexes 255 and 258 were obtained (Scheme 61). The spectroscopic data clearly showed that the olefinic group in 255 and the amino group in 258 are coordinated to the metal center <2000EJI1811>.

i. LiSiPh2(CMe=CHMe)

EtO

Me2N W(CO)5

ii. [Et3O]BF4 Ph2Si

W(CO)6

Me2NH Et2O, rt 71%

59%

W(CO)5 Ph2Si

254

253 Me2N hν

W(CO)5 Ph2Si

Et2O, –20 °C 93%

255

i. LiSiPh2NEt2 ii. [Et3O]BF4

EtO W(CO)5

W(CO)6 Ph2Si

60%

NEt2 256

hν Et2O, –20 °C 62%

MeNH2

H Me N

Et2O, rt

Ph2Si

95%

W(CO)5 NEt2 257

H Me N W(CO)5 Ph2Si NEt2 258

Scheme 61

Upon photolysis of the carbene complexes R12RSi(R2N)C¼M(CO)5 (M=Cr, Mo, W; or Ph3Si) the stable 16-electron carbene complexes R12RSi(R2N)C¼M(CO)4 are obtained. These species are stabilized by intramolecular interaction of one of the silicon substituents with the metal atom. Thus in Mes2SiH(Me2N)C¼W(CO)4 the Si–H group interacts with the tungsten atom. In the Ph3Si derivative, the W–Cphenyl distances indicate that the ipso carbon atom is mainly involved in the interaction with the metal atom. Despite the agostic interaction in the silylcarbene complexes, the coordination site is still accessible. Thus, the reaction of R12RSi(R2N)C¼M(CO)4 with CO, phosphines, phosphites, or isonitriles quantitatively yielded 18-electron carbene complexes cis-R12RSi(Me2N)C¼W(CO)4L (L=CO, RNC, R3P, (RO)3P) <1994OM1554, 1994ICA(220)73>. Formation of the silyl-substituted alkylidene tantalum and tungsten complexes from reactions of alkylidene complexes with silanes have been reviewed <2002JMOC(190)101>. Scheme 62 illustrates this synthetic methodology. Addition of the silanes H2SiRPh to the alkylidene complex 259 leads quantitatively to the disilyl-substituted alkylidene complexes 260. The reaction occurred exclusively with the alkylidene (¼CH–TMS) ligand, and the resulting complexes were found to be unreactive toward excess silane. More interestingly, addition of H2SiRPh to 261 led to the evolution of H2 and the formation of 1,10 -metalla-3-silacyclobutadiene complexes 262. The reaction of 261 with disilylmethane (H2PhSi)2CH2 also generates H2 and a metalladisilacyclohexadiene 263 <2001OM1504>. Novel products, unavailable by other routes, can thus be prepared. R12RSi¼Mes2HSi

704

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

TMS TMS

PMe3 Ta TMS TMS

H2SiRPh

TMS

TMS Ta

–H2, –PMe3

TMS

RPhHSi

TMS

Hexane, rt 260

259

H2SiRPh –2H2 Pentane, rt 44–78%

Ph R

TMS PMe3 Ta PMe3 TMS TMS 262

TMS TMS

PMe3 Ta PMe3TMS 261

PhH2Si

SiH2Ph

–2H2 Pentane, rt 10%

Ph TMS PMe3 H Si Ta PMe3 H Si TMS Ph TMS 263

R = Me, Ph

Scheme 62

6.22.3.2

Functions with a Formal Tin–Carbon and Lead–Carbon Double Bond

The synthesis and properties of low-coordinated compounds of tin and lead are collected in the recent review by Weidenbruch <2001MI621>. Stannaethene (TMS)2C¼SnMe2 is formed as a short-lived intermediate by reaction of (TMS)2BrC–Sn(Y)Me2 with LiR via (TMS)2LiC– Sn(Y)Me2 (Y = F, Br, PhO; R = organyl) and its existence was demonstrated by characteristic trapping experiments including the formation of thermolabile adduct with anthracene, which was used as a ‘‘store’’ for this compound <1998CEJ2571, B-1998MI106, 2000JOM(598)292, 2000JOM(598)304, 2000CJC1412>. Isolable compounds with a C¼Sn double bond are still extremely rare <1998CCR565>. The first members of this series with stability at room temperature were 264 and 265 prepared by Berndt and co-workers, both by the reaction between stannylenes and the cryptocarbene [(TMS)2C(BBut)2C] <1987AG(E)546>. More recently the preparation of stannaethenes 266 <1997JOM(530)255> and 267 <1999HAC554> has been described. The X-ray structure analysis of 266 reveals a strictly planar environment of the tricoordinated tin and carbon atoms and a slight twisting of the C¼Sn bond <1997JOM(530)255>.

TMS

But B

TMS TMS

TMS

But B

Sn TMS

B But 264

TMS TMS

TMS

B But

But N Sn SiMe2 N But

265

TMS TMS

But B B But

R1 Sn R2

266, R1 = R2 = 2-But-4,5,6-Me3C6H 267, R1 = 2-But-4,5,6-Me3C6H, R2 = (TMS)3Si

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

705

Other known compounds with tricoordinated carbon and tin atoms can better be described as Lewis base–acid adducts on account of their geometries and large C–Sn bond lengths. Examples of such compounds are zwitterionic adducts 268–270 prepared from the reaction of a nucleophilic carbene with tin(II) chloride <1995CB245>, a diarylstannylene <1995CC1157>, or diarylplumbylene <1999CC1131>. The related species 271 and 272 were also obtained directly from a stable carbene and the corresponding stannylene and plumbylene. Each of the crystalline adducts is a monomer, having an exceptionally long central bond between the three-coordinated carbon and the M atoms.

Pri

R N+

+ –

M R R

M N N RR

Pr i

269, M = Sn, R = 2,4,6270, M = Pb, R = 2,4,6-

R N

271, M = Sn, R = ButCH2

268, M = Sn, R = Cl <1995CB245> Pr3i C6H2 Pr3i C6H2

–

<1995CC1157>

272, M = Pb, R = ButCH2

<1999CC1131>

As mentioned in the previous section, reaction of an enetetramine with a coordinatively unsaturated metal complex is a standard method for the preparation of complexes with N-heterocyclic carbene ligands. Hahn and co-workers applied this strategy to the synthesis of a zwitterionic carbene–stannylene adduct via cleavage of a dibenzotetraazafulvalene by a stannylene. Thus reaction of the stannylene 273 with the tetramethyldibenzotetraazafulvalene 274 leads via C¼C bond cleavage in 274 to the carbene–stannylene adduct 275 <2001JOM(617/618)629> (Scheme 63).

N NH NH N

THF, 36 h,

Sn[N(TMS)2]2

83% N

N

N

N

N

N 274

N Sn N

Toluene, rt, 24 h N

N – Sn N

+

N N

67% N

273

275

Scheme 63

The molecular structure of 275 is similar to those of the carbene–silylene adduct reported by Lappert <1999CC755> or the carbene plumbylene adduct described by Weidenbruch <1995CC1157>. None of these species exhibits properties consistent with a C¼M double bond.

706

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

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Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 1995AG(E)1853 1995CB245 1995CB379 1995CB465 1995CB665 1995CB1207 1995CC1157 1995CC1425 1995COFGT(6)677 1995JOC7439 1995JOM(501)167 1995OM3762 1995S158 1995ZN(B)94 1996AG(E)271 1996AG(E)313 1996BCJ2673 1996CB219 1996CB223 1996CB367 1996CB471 1996CL695 1996JOM(511)239 1996JOM(519)107 1996JOM(524)147 1996HAC355 B-1996MI30 B-1996MI34 1996MI71 1996MI85 1996MI355 B-1996MI367 1996OM174 1996OM2683 1996OM3070 1996T1855 1996ZN(B)773 1996ZN(B)778 1997ACR486 1997AG(E)1095 1997AG(E)1469 1997AG(E)2162 1997BCJ2881 1997BSJ2881 1997CB89 1997CB1305 1997CB1519 1997CB1801 1997CC293 1997CC981 1997CCR(158)275 1997CL143 1997DOK(352)352 1997IC2151

707

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708

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

1997JA12410 1997JOC292 1997JOM(529)3 1997JOM(529)87 1997JOM(529)107 1997JOM(529)151 1997JOM(529)177 1997JOM(530)255 1997JOM(531)47 1997JOM(541)237 1997MI1 1997MI343 1997OM3188 1997RCR225 1997S1013 1997ZN(B)674 1998CCR565 1998CEJ44 1998CEJ469 1998CEJ2571 1998CL651 1998EJI381 1998JOM(557)37 B-1998MI1 B-1998MI106 B-1998MI238 B-1998MI857 1998OM1631 1998OM3593 1998S125 1999ACR913 1999AG(E)678 1999AG(E)3727 1999CC755 1999CC1131 1999CCR(182)175 1999EJI1607 1999HAC554 1999JA519 1999JA5953 1999JOM(572)239 B-1999MI1 1999MI113 1999MI269 1999OM529 1999OM1622

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Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal 1999OM1815 1999OM3228 1999OM4216 1999OM4603 1999PS(152)153 1999TL8579 1999ZAAC(625)1813 1999ZN(B)1 2000AG(E)1610 2000CEJ1773 2000CEJ3531 2000CJC1412 2000CL1390 2000CRV39 2000EJI1185 2000EJI1253 2000EJI1811 2000EJI2425 2000JA12880 2000JCS(D)3094 2000JOM(596)3 2000JOM(598)292 2000JOM(598)304 2000JOM(613)56 2000SCI(289)754 2000ZAAC(626)1141 2001CC1208 2001CEJ987 2001EJI387 2001EJI481 2001EJI2377 2001JOM(617/618)70 2001JOM(617/618)423 2001JOM(617/618)629 2001JOM(621)261 2001MI1 2001MI163 2001MI621 2001OM1276 2001OM1504 2001OM5707 2001ZAAC(627)1241 2002AG(E)1290 2002AG(E)3367 2002CC1618 2002EJI1607 2002HAC534 2002JA2506 2002JCS(D)2852 2002JMOC(190)101 2002JOM(643/644)202

709

I. Pailhous, H. Ranaivonjatovo, J. Escudie´, J.-P. Declercq, A. Dubourg, Organometallics 1999, 18, 1622–1628. P. L. Arnold, F. G. N. Cloke, T. Geldbach, P. B. Hitchcock, Organometallics 1999, 18, 3228–3233. L. Weber, M. H. Scheffer, H.-G. Stammler, B. Neumann, W. W. Schoeller, A. Sundermann, K. K. Laali, Organometallics 1999, 18, 4216–4221. L. Weber, G. Dembeck, Organometallics 1999, 18, 4603–4607. L. Rigon, H. Ranaivonjatovo, J. Escudie, Phosphorus Sulfur 1999, 152, 153–167. P. Michel, A. Rassat, Tetrahedron Lett. 1999, 40, 8579–8581. A. J. Arduengo III, R. Krafczyk, R. Schmutzler, W. Mahler, W. J. Marshall, Z. Anorg. Allg. Chem. 1999, 625, 1813–1817. F. Breitsameter, A. Schmidpeter, H. Noeth, J. Knizek, Z. Naturforsch. Teil B 1999, 54b, 1–7. M. Mickoleit, K. Schmohl, R. Kempe, H. Oehme, Angew. Chem., Int. Ed. Engl. 2000, 39, 1610–1612. J. Schwarz, V. P. W. Bo¨hm, M. G. Gardiner, M. Grosche, W. A. Herrmann, W. Hieringer, G. Raudaschl-Sieber, Chem. -Eur. J 2000, 6, 1773–1780. F. Breitsameter, A. Schmidpeter, H. No¨th, Chem. -Eur. J. 2000, 6, 3531–3539. N. Wiberg, S. Wagner, S.-K. Vasisht, K. Polborn, Can. J. Chem. 2000, 78, 1412–1420. S. Ito, M. Yoshifuji, Chem. Lett. 2000, 1390–1391. D. Bourissou, O. Guerret, F. P. Gabbaı¨ , G. Bertrand, Chem. Rev. 2000, 100, 39–91. L. Weber, S. Kleinebekel, A. Ru¨hlicke, H.-G. Stammler, B. Neumann, Eur. J. Inorg. Chem. 2000, 1185–1191. R. Streubel, S. Priemer, F. Ruthe, P. G. Jones, Eur. J. Inorg. Chem. 2000, 1253–1259. M. Schwarz, G. Kickelbick, U. Schubert, Eur. J. Inorg. Chem. 2000, 1811–1817. L. Weber, Eur. J. Inorg. Chem. 2000, 2415–2441. M. Bouslikhane, H. Gornitzka, J. Escudie´, H. Ranaivonjatovo, H. Ramdane, J. Am. Chem. Soc. 2000, 122, 12880–12881. B. Gehrhus, P. B. Hitchcock, M. F. Lappert, J. Chem. Soc., Dalton Trans. 2000, 3094–3099. C. D. Abernethy, A. H. Cowley, R. A. Jones, J. Organomet. Chem. 2000, 596, 3–5. N. Wiberg, T. Passler, S. Wagner, K. Polborn, J. Organomet. Chem. 2000, 598, 292–303. N. Wiberg, T. Passler, S. Wagner, J. Organomet. Chem. 2000, 598, 304–312. R. Streubel, M. Hobbold, S. Priemer, J. Organomet. Chem. 2000, 613, 56–59. T. Kato, H. Gornitzka, A. Baceiredo, W. W. Schoeller, G. Bertrand, Science 2000, 289, 754–756. J. Grobe, D. Le Van, J. Winnemo¨ller, A. H. Maulitz, B. Krebs, M. La¨ge, Z. Anorg. Allg. Chem. 2000, 626, 1141–1147. S. Ito, M. Yoshifuji, J. Chem. Soc., Chem. Commun. 2001, 1208–1209. M. Mickoleit, R. Kempe, H. Oehme, Chem. -Eur. J. 2001, 7, 987–992. A. Ziegler, H. Pritzkow, W. Siebert, Eur. J. Inorg. Chem. 2001, 387–391. K. Schmohl, H. Reinke, H. Oehme, Eur. J. Inorg. Chem. 2001, 481–489. I. V. Shevchenko, R. N. Mikolenko, E. Lork, G.-V. Ro¨schenthaler, Eur. J. Inorg. Chem. 2001, 2377–2383. D. Enders, H. Gielen, J. Organomet. Chem. 2001, 617/618, 70–80. R. Streubel, S. Priemer, J. Jeske, P. G. Jones, J. Organomet. Chem. 2001, 617/618, 423–434. H. F. Ekkehardt, L. Wittenbecher, M. Ku¨hn, T. Lu¨gger, R. Fro¨hlich, J. Organomet. Chem. 2001, 617/618, 629–634. M. Po¨tter, U. Ba¨umer, M. Mickoleit, R. Kempe, H. Oehme, J. Organomet. Chem. 2001, 621, 261–266. W. A. Herrmann, Th. Weskamp, V. P. W. Bo¨hm, Adv. Organomet. Chem. 2001, 48, 1–69. E. A. Romanenko, A. M. Nesterenko, Theoretical and Experimental Chemistry 2001, 37, 163–167. M. Weidenbruch, Main Group Chem. 2001, 24, 621–631. J. C. Garrison, R. S. Simons, J. M. Talley, C. Wesdemiotis, C. A. Tessier, W. J. Youngs, Organometallics 2001, 20, 1276–1278. J. B. Diminnie, J. R. Blanton, H. Cai, K. T. Quisenberry, Z. Xue, Organometallics 2001, 20, 1504–1514. T. L. Morkin, W. J. Leigh, T. T. Tidwell, A. D. Allen, Organometallics 2001, 20, 5707–5716. J. Grobe, A. Armbrecht, D. Le Van, B. Krebs, J. Kuchinke, M. Lage, E.-U. Wurthwein, Z. Anorg. Allg. Chem. 2001, 627, 1241–1247. W. A. Herrmann, Angew. Chem., Int. Ed. Engl. 2002, 41, 1290–1309. S. Ekici, D. Gudat, M. Nieger, L. Nyulaszi, E. Niecke, Angew. Chem., Int. Ed. Engl. 2002, 41, 3367–3371. H. Hayashi, H. Sonoda, K. Fukumura, T. Nagata, J. Chem. Soc., Chem. Commun. 2002, 1618–1619. A. Weiss, H. Pritzkow, W. Siebert, Eur. J. Inorg. Chem. 2002, 1607–1614. P. L. Arnold, Heteroatom Chem. 2002, 13, 534–539. T. Kato, H. Gornitzka, A. Baceiredo, W. W. Schoeller, G. Bertrand, J. Am. Chem. Soc. 2002, 124, 2506–2512. K. M. Lee, H. M. J. Wang, I. J. B. Lin, J. Chem. Soc., Dalton Trans. 2002, 2852–2856. J. R. Blanton, T. Chen, J. B. Diminnie, H. Cai, Z. Wu, L. Li, K. R. Sorasaenee, K. T. Quisenberry, H. Pan, C.-S. Wang, S.-H. Choi, Y.-D. Wu, Z. Lin, I. A. Guzei, A. L. Rheingold, Z. Xue, J. Mol. Catal. 2002, 190, 101–108. Y. El Harouch, H. Gornitzka, H. Ranaivonjatovo, J. Escudie´, J. Organomet. Chem. 2002, 643/644, 202–208.

710

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

2002JOM(643/644)253 C. Neumann, E. Ionescu, U. Schiemann, M. Schlenker, M. Bode, F. Ruthe, P. G. Jones, R. Streubel, J. Organomet. Chem. 2002, 643/644, 253–264. 2002JOM(654)233 W. Chen, B. Wu, K. Matsumoto, J. Organomet. Chem. 2002, 654, 233–236. 2002JOM(660)121 M. Muehlhofer, T. Strassner, E. Herdtweck, W. A. Herrmann, J. Organomet. Chem. 2002, 660, 121–126. 2002JOM(663)192 M. Niehues, G. Kehr, G. Erker, B. Wibbeling, R. Fro¨hlich, O. Blacque, H. Berke, J. Organomet. Chem. 2002, 663, 192–203. 2002OL1915 I. El-Sayed, T. Guliashvili, R. Hazell, A. Gogoll, H. Ottosson, Org. Lett. 2002, 4, 1915–1918. 2002OM1531 M. Bouslikhane, H. Gornitzka, H. Ranaivonjatovo, J. Escudie´, Organometallics 2002, 21, 1531–1533. 2002OM4919 T. Baumgartner, P. Moors, M. Nieger, H. Hupfer, E. Niecke, Organometallics 2002, 21, 4919–4926. 2002OM5204 V. Ce´sar, S. Bellemin-Laponnaz, L. H. Gade, Organometallics 2002, 21, 5204–5208. 2002OM5428 J. A. Chamizo, J. Morgado, M. Castro, S. Berne`s, Organometallics 2002, 21, 5428–5432. 2002PS(177)1571 L. Weber, M. Meyer, B. Quasdorff, Phosphorus Sulfur 2002, 177, 1571–1574. 2002PS(177)1609 S. Ito, M. Yoshifuji, Phosphorus Sulfur 2002, 177, 1609–1612. 2002TA1969 M. C. Perry, X. Cui, K. Burgess, Tetrahedron Asymmetry 2002, 13, 1969–1972. 2003CEJ704 F. E. Hahn, V. Langenhahn, N. Meier, T. Lu¨gger, W. P. Fehlhammer, Chem. -Eur. J. 2003, 9, 704–712. 2003IC2572 M. Poyatos, M. Sanau´, E. Peris, Inorg. Chem. 2003, 42, 2572–2576. 2003JA1128 C. D. Abernethy, G. M. Codd, M. D. Spicer, M. K. Taylor, J. Am. Chem. Soc. 2003, 125, 1128–1129. 2003JCS(D)699 A. A. D. Tulloch, S. Winston, A. A. Danopoulos, G. Eastham, M. B. Hursthouse, J. Chem. Soc., DaltonTrans. 2003, 699–708. 2003JOM(671)183 C. A. Quezada, J. C. Garrison, C. A. Tessier, W. J. Youngs, J. Organomet. Chem. 2003, 671, 183–186. 2003OM440 M. Poyatos, P. Uriz, J. A. Mata, C. Claver, E. Fernandez, E. Peris, Organometallics 2003, 22, 440–444. 2003OM907 A. Fu¨rstner, G. Seidel, D. Kremzow, C. W. Lehmann, Organometallics 2003, 22, 907–909. 2003OM1110 M. Poyatos, J. A. Mata, E. Falomir, R. H. Crabtree, E. Peris, Organometallics 2003, 22, 1110–1114.

Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B, or a Metal

711

Biographical sketch

Vadim D. Romanenko was born in Lugansk, Ukraine, in 1946. He studied at the Institute of Chemical Technology (Dnepropetrovsk) and received his Ph.D. degree there under the direction of professor S. I. Burmistrov. Since 1975 he has been working at the National Academy of Sciences of Ukraine from which he earned his Doctor of Chemistry degree in 1988. He became a full professor in 1991. He has been a visiting scientist at the Centre of Molecular and Macromolecular Studies in Lodz (Poland), the Shanghai Institute of Organic Chemistry (China), the University of Pau & des Pays de l’Adour (France), the University Paul Sabatier (France), the University California Riverside (USA). His research interests include a wide range of topics at the border between organic and inorganic chemistry, in particular the chemistry of multiply bonded heavy main group elements. He is the author of approximately 260 papers on organoelement chemistry. He is also author of numerous reviews and two monographs on low-co-ordinated phosphorus compounds.

Valentyn Rudzevich was born in Kazatin, Ukraine, in 1968. He received his Diploma degree in 1992 from Taras Shevchenko Kiev State University. Since 1992 he has been working at the Institute of Organic Chemistry of National Academy of Science of Ukraine, from which he received his Ph.D. degree under the supervision of professor V. D. Romanenko in 1997. Afterwards, he carried out postdoctoral studies at Universite´ Paul Sabatier (Toulouse, France), University of California Riverside (USA) and Johannes Gutenberg Universita¨t Mainz (Germany). On his return to Kiev, he joined the Institute of Organic Chemistry where he is presently a scientist researcher. His research interests are focused on organoelement compounds, shortlived intermediates, and co-ordination chemistry.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 661–711

6.23 Tricoordinated Stabilized Cations, Anions, and Radicals, +CX1X2X3, CX1X2X3, and _CX1X2X3 M. BALASUBRAMANIAN Pfizer Global Research and Development, Ann Arbor, MI, USA 6.23.1 CARBON-CENTERED CATIONS BEARING THREE HETEROATOM FUNCTIONS 6.23.1.1 Introduction 6.23.1.2 Cations Bearing Three Halogens 6.23.1.3 Cations Bearing Halogen and Chalcogen Functions 6.23.1.4 Cations Bearing Halogen, Other Elements, and (Possibly) Chalcogen Functions 6.23.1.4.1 Cations bearing two halogen and one nitrogen functions 6.23.1.4.2 Cations bearing two halogen and one other heteroatom functions 6.23.1.4.3 Cations bearing one halogen, one chalcogen, and one nitrogen functions 6.23.1.4.4 Cations bearing one halogen and two nitrogen functions 6.23.1.5 Cations Bearing Three Chalcogen Functions 6.23.1.5.1 Three oxygen functions 6.23.1.5.2 Three sulfur functions 6.23.1.5.3 Three selenium functions 6.23.1.6 Cations Bearing Chalcogen and Nitrogen Functions 6.23.1.6.1 Two oxygen and one nitrogen functions 6.23.1.6.2 Two sulfur and one nitrogen functions 6.23.1.6.3 Two selenium and one nitrogen functions 6.23.1.6.4 Two different chalcogen and one nitrogen functions 6.23.1.6.5 One oxygen and two nitrogen functions 6.23.1.6.6 One sulfur and two nitrogen functions 6.23.1.6.7 One selenium and two nitrogen functions 6.23.1.7 Cations Bearing Chalcogen, Metal, and (Possibly) Nitrogen Functions 6.23.1.8 Cations Bearing Three Nitrogen Functions 6.23.1.9 Cations Bearing Nitrogen and Other Element Functions 6.23.1.10 Cations Bearing Phosphorus and Silicon Functions 6.23.2 CARBON-CENTERED CARBANIONS BEARING THREE HETEROATOM FUNCTIONS 6.23.2.1 Carbanion Bearing Three Halogens 6.23.2.2 Carbanions Bearing One Halogen and Two Sulfur Functions 6.23.2.3 Carbanions Bearing One Halogen and Two Phosphorus Functions 6.23.2.4 Carbanions Bearing Three Nitrogen Functions 6.23.2.5 Carbanions Bearing Three Sulfur Functions 6.23.2.6 Carbanions Bearing Three Phosphorus Functions 6.23.2.7 Carbanions Bearing One Phosphorus and Two Sulfur Functions 6.23.2.8 Carbanions Bearing One Nitrogen and Two Sulfur Functions 6.23.3 CARBON-CENTERED RADICALS BEARING THREE HETEROATOM FUNCTIONS

713

714 714 714 714 714 714 714 714 715 716 716 716 717 717 717 717 718 718 718 719 719 719 720 721 722 722 723 723 723 723 723 723 724 724 724

714 6.23.1

Tricoordinated Stabilized Cations, Anions, and Radicals CARBON-CENTERED CATIONS BEARING THREE HETEROATOM FUNCTIONS

6.23.1.1

Introduction

Carbocations with three heteroatom substitutents attached to carbon are popular reaction intermediates. They are stabilized by electron donation from lone pairs of electrons from heteroatoms into the vacant -orbitals on carbon. Nitrogen is the most effective of the three common heteroatoms (O, N, S) with respect to electron pair donation. The presence of just one nitrogen function can enable the salt of a formal carbocation to be more stable and isolable. With one nitrogen atom attachment, there are two resonance hybrid structures possible, carbenium ion 1 (+ve charge on carbon) and iminium ion 2 (+ve charge at nitrogen). Such compounds are generally considered to have the charge on nitrogen. Such positively charged derivatives of compounds are considered in Chapter 6.20. When the carbocation has more than one heteroatom function attachment then there are further possibilities for charge delocalization.

6.23.1.2

Cations Bearing Three Halogens

Trihalomethyl cations CX3 (X = Br, Cl, F) have been generated at low temperature from tetrahalomethanes on reaction with antimony pentahalides, and they have been reviewed earlier <1995COFGT(6)725>. Bromochlorofluoromethylium ion has been generated from bromochlorodifluoromethane <1997JPC(A)8489>. The -electron donor ability of fluorine is more than offset by its electron withdrawing inductive effect, thus the trifluoromethyl cation is less stable than the other trihalomethyl cations.

6.23.1.3

Cations Bearing Halogen and Chalcogen Functions

Fluoroformic acid is an intermediate in the oxidation of fluorocarbons and ozonolysis of fluoroalkenes. Its potential role in the depletion of the ozone layer in the stratosphere was explored in the early 1990s. Neutral fluoroformic acid does not exist because of its autocatalytic decomposition to HF and CO2. However, its conjugate acid and base protonated fluoroformic acid [FC(OH)+ 2 ] and fluoroformate ion ], respectively, are expected to be more stable due to its resonance stabilization. Protolytic [FCO 2 ionization of t-butyl fluoroformate with fivefold excess of FSO3H/SbF5 in SO2ClF resulted in a deep yellow solution containing the carbocation +CF(OH)2 <1997AG(E)1875>. Bromotrifluoromethane, further reacted with H3O+ to produce the carbocation +CF2OH <1997JPC(A)8489>.

6.23.1.4 6.23.1.4.1

Cations Bearing Halogen, Other Elements, and (Possibly) Chalcogen Functions Cations bearing two halogen and one nitrogen functions

The preparative methods for dihaloiminium salts such as N,N-dimethyldihaloiminium halides 3 (X = Cl, Br, I) and pyrrolidinedichloroiminium chloride 4 have been reviewed previously <1995COFGT(6)725>. These salts are important reagents and have a wide variety of synthetic applications. No further development has been found on these types of salts.

6.23.1.4.2

Cations bearing two halogen and one other heteroatom functions

Several transition metal complexes exist in which CX2 acts as a ligand. Such metal complexes have overall positive charge and have been reviewed <1995COFGT(6)725>. No further development has been seen for these types of transition metal complexes since 1995.

6.23.1.4.3

Cations bearing one halogen, one chalcogen, and one nitrogen functions

The chlorination of N-methylbenzothiazole-2-selone 5 and 1,1-dimethylselenourea 7 with SO2Cl2 and chlorine produced corresponding benzothiazolium 6 and uronium 8 salts, respectively, and X-ray studies have been conducted for these salts <1999JCS(D)4245>.

715

Tricoordinated Stabilized Cations, Anions, and Radicals X + Y

X

NR2

Y 1

S + Cl N SO2Cl– Me 6

Se N Me 5

6.23.1.4.4

R N + X– X R 3 X = Cl, Br, F

2

S

X

X

+ R N R

X–

N + X 4

Me Me N Se H2N

Me Me N + Cl H2N

7

SeCl5–

8

Cations bearing one halogen and two nitrogen functions

Tetramethylfluoroformamidinium hexafluorophosphate (TFFH) 9 a nonhygroscopic salt, stable under ambient conditions, was obtained from 10 with excess of anhydrous KF <1995JA5401>. The salt 10 was prepared previously from tetramethylurea using phosgene. A new improved synthetic procedure for 10 from tetramethylurea using oxalyl chloride has been reported <1989TL1927>. TFFH appears to be an ideal coupling reagent for solid-phase syntheses, being readily available, inexpensive and capable of providing peptides of high quality <2000OL3539>. A new and convenient method for the solid-phase preparation of pentasubstituted guanidines involves the use of aminium/uranium salt-based reagents. These compounds have been used mainly as coupling agents in peptide synthesis and they activate the carboxyl group of the amino acids <2000OL3539>. Bispyrrolidinefluoromethylium tetrafluoroborate 11 is a convenient reagent for the solid-phase synthesis of a range of peptides incorporating sensitive amino acids and 11 has been prepared from 1,10 -carbonylbispyrrolidine 13a using oxalyl chloride <1998CL671>. Bispiperidinechloromethylium tetrafluoroborate 12 was prepared from 1,10 -carbonylbispiperidine 13b via deoxygenation using phosgene <2000OL3539>. Pyrrolidine-1-carboxylic acid dialkylamides 14 and 15 reacted with COCl2 to form N,N-dialkyl-N-pyrrolidinochloromethylcarbenium salts 16 and 17 <2000OL3539>. 2-chloro-1,3-dimethylimidazolinium chloride 19 has been prepared from 1,3-dimethylimidazolidine-2-one 18 and oxalyl chloride <1986T6645>. 2-Chloro-1,3-dimethylimidazolinium chloride is a powerful dehydrating agent and 19 is equivalent to dicyclohexylcarbodiimide (DCC). The advantages of 19 are low cost, nontoxic, and easy removal of product from the reaction mixture by simple washing with water. Chiral guanidines prepared from 19 can be considered as super bases due to their strong basic character <2000JOC7770>. The synthetic utility of 19 has been well demonstrated as an effective dehydrating agent in the following synthetic reactions: esterification of hindered alcohol, acylation of 1,3-diones (cyclic), dehydration of oximes to nitriles (aromatic), and dehydration of benzamide to nitriles <1999JOC6984>. Isocyanides, isothiocyanates, and carbodiimides were synthesized from formamides, dithiocarbamates, and thiourea, respectively <1999JOC6984>. 2-Chloro-1,3-dimethylimidazolinium chloride is used as a coupling agent for the conversion of trimesitylchlorosilane to hexamesityldisilane <1984JOMC(264)179>. Further reactions of 19 are explored with L-valinol, benzamide, and methyl(S)-1-phenylethylamine to produce more useful and novel compounds <2000JOC7770>. Me + N N Me Me X PF–6 or BF–4

Me

N O

14 R = Me, 15 R = Et

Cl– or BF–4

N+ N

n(H2C)

(CH2)n N

X

N +

R N Cl

13a n = 1; 13b n = 2

Me

Me N R PF6–

16 R = Me, 17 R = Et

N O

11 n = 1, X = F 12 n = 2, X = Cl

9 X = F, 10 X = Cl

R N R

(CH2)n

n(H2C)

Me

N O 18

Me

N

+

N

Cl– or BF4–

Cl 19

716

Tricoordinated Stabilized Cations, Anions, and Radicals

6.23.1.5

Cations Bearing Three Chalcogen Functions

6.23.1.5.1

Three oxygen functions

Several examples of tris(alkoxy)methylium salts were reviewed earlier and no further advances have occurred in this area since 1995 <1995COFGT(6)725>. Trimethylsilylacetylene 20 has been deprotonated with BuLi and subsequently reacted with 21 to give 1,1,1-triethoxy2-trimethylsilylpropyne 22, thus exploring the synthetic utility of triethoxycarbenium tetrafluoroborate 21 <1997TL6803>. Protonation of dimethyl carbonate by the super acids system HF, MF5 (M = As, Sb) afforded dimethoxyhydroxycarbenium hexafluorometallates 23, which are colorless, moisture sensitive salts. These salts are soluble in SO2, and are stable at 70 C for several weeks <2000EJI1261>.

6.23.1.5.2

Three sulfur functions

Stable salts of carbenium ions bearing three sulfur functions have been reported. The methods for their preparation are analogous to those used for the tris(alkoxy)carbenium ions but, since it is much easier to alkylate sulfur than oxygen, a wider range of alkylating agents can be used. Substituted 1,3-dithiolane- and 1,3-dithioles-2-thiones 24 and 26 were also alkylated using various methylating agents to provide corresponding salts 25 and 27. Thiones are often alkylated with the most commonly used methylating agents such as alkyl halides and methyltrifluoromethane sulfonate <1997TL81, 1991S26, 2000CL842, 1998CC361, 1998JMAC1185, 1999JCS(P2)505>, although dimethyl sulfate has been used occasionally <1991S26>. 4,5-Disubstituted 1,3-dithiole-2-thiones 26a and 26b were methylated using methyltrifluoromethane sulfonate to provide corresponding salts 27a and 27b in quantitative yield. Derivatives of 1,3-dethiole-2-thiones 28, 29 were methylated to the corresponding 1,3-dithiolium iodides 30, 31, and 31 underwent desulfurization with subsequent self-coupling to afford the dimeric product 32 <1991S26, 1995JPR299>.

OEt – EtO + BF4 OEt 21

Me Si Me Me 20

R1

R1

S

R2

S

R2

R1

S

R2

S

S + S

S Me

27

S R

R

R S + S

S

28 R = H 29 R = SMe

Me

I– or CF3SO–3

R

R

MF–6 M = As, Sb

26a, 27a R1R2 = (S–CH2CH2–S) 26b, 27b R1 = R2 = CH2–S–(C=O)Me

R S

R2

26

24a, 25a R 24b, 25b R1 = R2 = Me

R

S S

1 = R2 = H

R

23

Me

25

R

O

22

CF3SO–3 24

Me HO + O

OEt OEt OEt

R1

S + S

S

Me Me Si Me

R 30 R = H 31 R = SMe

Me S I–

R R

S

S

S

S

R R R

R 32 R = SMe

717

Tricoordinated Stabilized Cations, Anions, and Radicals

Several coupling products of substituted thienodithiolylidenefluorene 35 were prepared from substituted fluorene and thienodithiolane carbenium ion 34, which in turn was derived from thienodithiole-2-thione 33 <1999JCS(P2)505>. The degree of intramolecular charge transfer (ICT) in dithiolylidene fluorenes bearing fused thiophene has been investigated by UV-VIS spectroscopy <1999JCS(P2)505>. Tris(trifluoromethyl(chalcogenato)carbenium ions 36 and 37 were prepared from fluoro tris(trifluoromethylthio)methane and fluoro tris(trifluoromethylseleno)methane <1996CB1383>. Tris(chalcogenato)carbenium ion 38 was generated from CBr4 and ArSCu <1996AG(E)300>. Further reaction of tris(trifluoromethylthio)carbenium hexafluoroarsenate 36 with benzene and anisole produced benzophenone and 4,40 -dimethoxybenzophenone, which are products of hydrolysis of the diphenylmethane intermediate <1995CB435>.

6.23.1.5.3

Three selenium functions

Tris(trifluoromethylseleno)carbenium hexafluoroarsenate 37 was prepared from tetrakistrifluoromethylselenylmethane <1996CB1383> and is stable at 20 C. Trisisoopropylbenzene selenide reacted with tetrabromomethane to form tris(triisopropylbenzene)selenide 39 <1996AG(E)300>.

S

S S

S

CF3SO–3

S + S

33

S Me

Ar X X

+

XCF3

37 X = Se,

6.23.1.6 6.23.1.6.1

Me Me

X

Ar PF6–

S 35

34

F3CX + XCF3

36 X = S, AsF6–

S S

Ar

Ar =

Me *

S

Me

38 X = S, AsF6– 39 X = Se, PF6–

Me Me

Cations Bearing Chalcogen and Nitrogen Functions Two oxygen and one nitrogen functions

Mono-O-protonated carbamic acids and N-methyl carbamate were prepared using super acids (FSO3H/ SO2ClF and FSO3H:SbF5/SO2ClF) at 78 C, and these salts were characterized by 1H, 13C, 15N NMR spectroscopy <1998JOC7993>. A stable salt of 1,9-diethoxy-1-methoxy-3,5,7,9-tetraphenyl-2,4,6,8tetraazanonatetraenylium hexachloroantimonate 41 was prepared from the corresponding ester 40, by regioselective O-alkylation with triethyloxonium hexachloroantimonate <1996MI371>. Further reaction of dimethylaminodiethoxycarbenium tetrafluoroborate 42 with N,N-dimethylamine produced bis(dimethylamino)diethoxymethane <2000JPR256>.

6.23.1.6.2

Two sulfur and one nitrogen functions

Methylations of few cyclic dithiocarbamates with dimethyl sulfate yielded corresponding thiocarbamate salts and have been reviewed previously <1995COFGT(6)725>. Dithiocarbamate salts 45 and 46 are most often prepared by S-alkylation of dithiocarbamates 43 and 44 <1995JOC2330>.

718

Tricoordinated Stabilized Cations, Anions, and Radicals

6.23.1.6.3

Two selenium and one nitrogen functions

Reaction of 2-chloro-1,3-diselenoazolium tetrafluoroborate 47 with morpholine to form 1,3diselenazole-2-morpholinium salt 48 has been reported <1987PS187>.

6.23.1.6.4

Two different chalcogen and one nitrogen functions

Alkylation of 3-methyl-5-phenyl-3H-1,3,4-oxadiazole-2-thione 49 with MeI produced salt 50 <1995JOC2330>. Alkylation of diethylthiocarbamic acid O-p-tolyl ester 51 with triethyloxonium tetrafluoroborate produced a moisture sensitive, colorless solid stable salt 52 <2001EJO83>.

6.23.1.6.5

One oxygen and two nitrogen functions

Alkylation of substituted ureas with 21 primarily produced O-alkylated stable and isolable uronium salts. This work has already been reviewed <1995COFGT(6)725>. It is interesting to note that in some cases, N-alkylation of tetraalkylurea competes with O-alkylation. Thus an alternative synthetic strategy is employed for the preparation of uronium salts starting from N,N,N0 ,N0 -tetramethylchloroformadinium chloride whereby N-alkylation can be avoided. N,N,N0 ,N0 -Tetramethyl(succinimido)uronium tetrafluoroborate 54 and 2-(1H-benzotriazol-1yl)-1,1,3,3-tetramethyluronium hexafluorophosphate 56 have been used as coupling agents in solid-phase peptide synthesis. They are excellent activating agents and reduce racemization during condensation of peptide segments. They are useful tools for the formation of active esters suitable for coupling in mixed aqueous or organic media.

O

Et R + O

O R

O Et

40

O

N

N

Me2N + OEt

R=

SbCl–

6

OEt

BF 4–

42

41

Me N

S Me

Me N R

S

R

43 R = H, 44 R = Me

S N N

O

N

N

Me

S Me + I– S Me

Se Cl + – Se BF 4

45 R = H, 46 R = Me

Me S + N N

O

Me I–

Se N + Se 48

47

Me

Me N

Me

S

N

O

Me

S BF–4

+ O

Me 49

50

O BF–4

Me 52

51

N

O

N OH

Me Me O N Me + N N Me O

O

O 53

BF4– 54

N N N N – K+ O 55

N

PF–6 Me O Me N + N Me Me 56

Tricoordinated Stabilized Cations, Anions, and Radicals

719

N-Hydroxysuccinimide 53 reacted with 10 to form N,N,N0 ,N0 -tetramethyl(succinimido)uronium tetrafluoroborate 54 <1989TL1927>. Several esterification reactions have been reported in which N,N,N0 ,N0 -tetramethyl(succinimido)uronium tetrafluoroborate 54 is used as a coupling agent. The salt shown in 54 has been used as a feed stock to produce several other useful coupling agents <1997JA640, 1999HCA1311, 1999BMCL2229, 1999JA5860, 2000S707, 2000BMC2359, 2002OL1075>. 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate 56 was prepared from benzotriazole-N-oxide 55 using 10 <1989TL1927, 1984S572, 2002AG(E)442> and the salt given in 56 is used as a coupling agent for several esterification reactions <1999T1129, 2000BMCL13, 2000AG(E)1626>.

6.23.1.6.6

One sulfur and two nitrogen functions

There has been considerable interest in the usage of isothiuronium salts in membranology and in organic synthesis. These salts are used to regulate free radical oxidation in biological membranes. Functional transformation of CH2X to CH2SH via isothiuronium salt has been shown to have a great deal of synthetic utility in organic synthesis. S-Alkylation of tetramethylthiourea 57, with MeI gave isothiuronium salt 58 <1995JOC2330>. Salt of disulfide 59 was obtained from 57 via oxidation with bromine <1997JCS(D)1857>. 2-Bromo-2H-1,4-benzoxazin-3(4H)-one 60 and 2-bromo-2H-1,4-benzothiazin-3(4H)-one 61 were converted into corresponding isothiuronium salts 62 and 63 by reaction with thiourea in acetone <1996JHC1623>. Further, these salts were converted to the corresponding mercapto derivatives by alkaline hydrolysis. Isothiuronium salt 65 was obtained from 3-chloro-2-chloromethylpropene 64 and thiourea via S-alkylation <1996AJC1261>. The S-alkylation of thiophosphate 66 by thiourea, followed by ring opening, produced thiuronium salt 67 <1996RJGC1072>. Bicyclic thiophosphate 68 reacted with thiourea to provide a high yield of betaine 69, which is of certain bioregulating interest as a radioprotector, and the overall reaction is a thione-thiol isomerization (ring-opening products) <1996RJGC1362>. Disodium[(3-methylthioureido)methylene]bisphosphonate 70 is easily alkylated in aqueous solution with MeI to give stable and isolable thiuronium salt 71 <1996RJGC1442>. 4-Nitrophenylisothiuronium salt was obtained from 4-nitrobenzenethiol and NH2CN <1997JCS(P2)1555>. 6,60 -Bischloromethyl-[2,20 ]bipyrazinyl isothiuronium salt 72 was obtained from 6,60 -bischloromethyl-[2,20 ]bipyrazine and thiourea <1999EJO1427>. Tetramethyluronium and -thiouronium salts 75 and 76 were prepared from N-hydroxy-2-oxopyridine 73 and N-hydroxy-2-mercaptopyridine 74, respectively <1999JOC8936>. Novel carbanion ionophores based on thiuronium derivative 78 have been prepared via S-alkylation of N-benzyl-N-butylthiourea 77 using MeI, and their application to ion selective electrodes has been examined <2001CL382>.

6.23.1.6.7

One selenium and two nitrogen functions

Synthesis of dipyridoimidazolone 80 from 6H-dipyridoimidazole-6-selone 79, was accomplished via Se-alkylation of 79 with MeI followed by hydrolysis of the resulting salt, 6-(methylselan)dihydroimidazolium iodide 81, produced 80 <2000EJI1935>.

6.23.1.7

Cations Bearing Chalcogen, Metal, and (Possibly) Nitrogen Functions

General methods for the preparation of cationic carbene complexes of mercury and platinum complex have been reviewed <1995COFGT(6)725>. Lewis acid adducts of stable nucleophilic carbene 82 with various metals have been reported <1995AG(E)487>.

720

Tricoordinated Stabilized Cations, Anions, and Radicals S

NMe2

Me2N

S

Me Br–

Me2N + NMe2

2Br– S NMe2 S + NMe2

58

57

Br

X

Me2N + Me2N

X N H

O

59

S + O

NH2 NH2

Br –

62 X = O, 63 X = S

60 X = O, 61 X = S

H2N + NH2 O H2N Cl

S

+ H2N

Cl

S 2Cl–

64

O O P S O

O

65

S + H2N O S P O O–

O O O

S O

N

Me

P ONa O OH

H H N + N

Me

S

O OH P – O

P ONa O OH

+

71

Me

+ Me N X N Me OH BF4–

N OH

S

S

N

H

N H Bu

N

Ph

H

Me

N + N I– Bu

Ph

+

H2N

Me X

S

2Cl–

O OH P ONa

70

N N

S

NH2 72

73 X = O 74 X = S

N

77

75 X = O 76 X = S

N N + X

79 X = Se, 80 X = O

6.23.1.8

H N

69

N

H2N

Me

O

H N

67

O

68

H2N

O P S O–

O

66

H2N O O P O S

S

O

O

NH2 + NH2

I–

78

N

Se Me 81

Cations Bearing Three Nitrogen Functions

Preparative methods for guanidines have been described in Chapter 6.21. Guanidines are strong bases and also excellent nucleophiles. Several guanidium salts have been prepared by protonation or alkylation of guanidine <1996JPR403>. Tris(pyrrolidine)carbenium chloride 83 has been prepared from fluorobis-(1-pyrrolidinyl)carbenium chloride 11 by reacting with pyrrolidine <1996JPR403>. Reaction of phenylbis(3-aminobenzene)phosphine 84 with dimethylcyanamide 85 provided guanidinium phosphines 86 in high yield <1997JOC2362>. Deprotonation of PhCOCHPhCO2Me 87 with tetrakis(dimethylamine)methane led to a stable salt 88, which belongs to a very rare species of salts that consists of a heteroatom stabilized carbocation and a heteroatom stabilized carbanion <1996MI2131>. Triazidocarbenium salt is prepared from tetrachloromethane using NaN3 <1997JA8802>, and 89 is ideally suited for high energy density material such as propellants and explosives. Conversion of 89 to more energetic salts containing anions such as [N(NO2)2] and (ClO4)] has been reported <1997JA8802>. Quinolinotriazole-N-oxide 90 was converted into the corresponding guanidinium salt 91 using 10 <2001OL2793>.

721

Tricoordinated Stabilized Cations, Anions, and Radicals 6.23.1.9

Cations Bearing Nitrogen and Other Element Functions

N,N-Dimethylformamide acetal reacted with elemental selenium to give selenocarbonic acid derivative 92, which was further converted into N,N-dimethylcarbamidic acid Se-methylester 93 via alkylation with MeI <1996JPR403>. Alkylation of N-methylbenzoselenazole-2-thione 94 and 3,3-ethylenebis(benzoselenoazole-2-thione) 96 with the strong alkylating agent, diethoxycarbonium tetrafluoroborate, produced corresponding salts 95 and 97, respectively <2002JCS(P1)1568>.

+

N

N

Li2– + O Li2–

N

N

+

O+

N N C + N Cl–

Ph P

H2N

NH2

84 83

82

Me2N + NMe2

Me N CN

Ph P

HN

Me

Me2N +

O

NMe2

O

Ph

NH

Me O

2Cl– 85

Ph

87

86

Me2N + +C(NMe

–O

N3 + N3

Ph

2 )3

O

Ph

Me

N

N3 SbCl –6

N

89

90

O 88

MeO

MeO + Me2N

Se Me2N

Se Me

N N OH

Me N

I–

Me BF4– N + S Se

S Se

93

92

94

95

S 2BF4– N

S N

Se

S

N + N N N O– 91

N

+

Se

N +

Se

S Se 97

96

..

+ P C N –

P C N

+ P C N BF4–

98

98a

MeO

OMe S 99

MeO + OMe SMe 100

X–

NMe2 PF6–

722

Tricoordinated Stabilized Cations, Anions, and Radicals

Few cationic carbene complexes and their salts have been prepared in which the cation bears nitrogen and one phosphorus functions. Synthesis, structure, stability, and reactivity of (amino) (phosphino) carbenes has been reported <2002JA6806>. Treatment of carbene, [(t-Bu)2PCN (i-Pr)2] 98 with 1 equiv. of BF3Et2O, led to quantitative formation of carbene complex 98a, which has been characterized by NMR spectroscopy <2002JA6806>. Carbenium ion 100 bearing sulfur and two oxygen functions has been produced via S-alkylation of thiocarbonic acid O,O0 -dimethyl ester 99 with iodomethane <1995JOC2330>.

6.23.1.10

Cations Bearing Phosphorus and Silicon Functions

The C-alkylation of 1,3-diethyl-4,5-dimethylimidazol-2-ylidene 101 with iodotrimethylsilane produced 1,3-diethyl-4,5-dimethyl-2-(trimethylsilyl)imidazolium iodide 102 <1995CB245>. Rapid valence isomerization of phosphaalkene-phosphenium cation 103a to cationic diphosphene 103b was observed and 103b was characterized by 31P NMR spectroscopy, but not isolated <1991TL2775>. 1,2-Silyl migration in aromatic carbenes via intermolecular silyl exchange has been reported <1998JA9100>. Since aromatic carbenes are very good nucleophiles, attack of triphenyltriazole carbene 104 on the silyl group of cation 105 resulting in the formation of C-silyl substituted triazolium salt 106 along with methyltriazole <1998JA9100>. Several crystalline adducts 109 were prepared from benzimidazole carbene 107 by reacting with derivatives of 108 (silylene germylene, stannylene, or plumbylene). The CM bond is electrostatic in nature with the carbene moiety as an electron donor and the metal fragment as an electron acceptor <2000JCS(D)3094>.

Et N

Et Me N + Si Me N Me Et

..

N Et 101

I–

Et2N Et2N

103a

102

Me Si Me

N

..

N N Ph

Ph

Ph Me N Si N N Me Ph

105

104

N N

107

6.23.2

103b

+

N + N N CF3SO3– Me

..

P P N

CF3SO3–

CF3SO3–

Ph Ph

Et2N + Et2N

+ P P N

N M N

108 M = Si, Ge, Sn, Pb

CF3SO3–

106

N + N

N M– N

109 M = Si, Ge, Sn, Pb

CARBON-CENTERED CARBANIONS BEARING THREE HETEROATOM FUNCTIONS

Carbanionic carbons bearing three different heteroatom functions were not covered in the earlier review <1995COFGT(6)725>. The current review includes several such carbanionic carbon-

Tricoordinated Stabilized Cations, Anions, and Radicals

723

bearing nitrogen, phosphorus, and sulfur functions. They are stable at low temperature, isolable, and are useful intermediates in organic synthesis. Attachment of phosphorus and sulfur functions to carbanionic carbon causes an increase in carbanion stability due to an overlap of the unshared electron pair with an empty d-orbital (pd bonding). Electron withdrawing groups such as NO2 at the -position also stabilize carbanions.

6.23.2.1

Carbanion Bearing Three Halogens

The N-trimethylsilylimidophosphenous acid derivative from 2,2,6,6-tetramethylpiperidine reacts with bromotrichloromethane readily to afford the stable salt 110. The ion pair 110 is stable and provides an environment for sterically favorable nucleophilic substitution of the trichloromethide anion rather than bromide ion. The possibility that this reaction proceeds via a radical mechanism cannot be ruled out <1984JGU278>.

6.23.2.2

Carbanions Bearing One Halogen and Two Sulfur Functions

The 2,2,4,4-tetrabromo-1,3-dithietan-1,1,3,3-tetroxide 111 is cleaved by tris(dimethylamine)sulfonium hexafluoride silicate 112 to form the intermediate salt 113. The fluoride ion from 113 can be abstracted by SiF4 and quinuclidine and the resulting perhalogenated mesylsulfene (Br3SO2C(Br)¼SO2 is stabilized by S-coordinated quinuclidine <1990ZN(B)1187>.

6.23.2.3

Carbanions Bearing One Halogen and Two Phosphorus Functions

Phosphonoalkylation of acylchlorophosphinate 114 in the presence of excess of LDA leads to direct generation of stable lithiated methylenediphosphonate anion 115. Further 115 can be either protonated in acidic medium to provide tetrasubstituted methylenediphosphonate or alkylated. When aliphatic or aromatic aldehydes are added, spontaneous formation of vinyl phosphonates is observed <1986JOMC(304)283>.

6.23.2.4

Carbanions Bearing Three Nitrogen Functions

Deprotonation of trinitromethane with tetrabutylammonium hydroxide results in trinitromethide 116a. Deprotonation of trinitromethane with benzyltrimethylammonium hydroxide provides 116b, which is unstable even at 15 C and it undergoes decomposition with explosive release of gases when stored in the dark at room temperature <1985JA7880>.

6.23.2.5

Carbanions Bearing Three Sulfur Functions

Interaction of tris(fluorosulfonyl)methane and tris(trifluoromethylsulfonyl) with aryldiazonium chloride in water leads to the formation of stable water-insoluble salts 117a and 117b, respectively <1983TL87, 1990JOU584>. Benzenediazonium bis(fluorosulfonyl)phenoxysulfonyl methanide 118, a colorless crystalline solid stable at 0 C is produced by simple mixing of benzenediazonium chloride with bis(fluorosulfonyl)phenoxysulfonylmethane <1991JOU426>.

6.23.2.6

Carbanions Bearing Three Phosphorus Functions

Bis(diphenylphosphino)diphenylthiophosphorylmethane is readily deprotonated with LiOH to produce the carbanion 119 <1988PS79>. Tetrabutylammonium tris(diphenylthiophosphinoyl)methide 120 has been produced from tris(diphenylthiophosphinoyl)methane and isolated as a stable solid, which is a useful synthetic intermediate in the formation of cage complexes via coordination with metal cations <1982CC930>.

724

Tricoordinated Stabilized Cations, Anions, and Radicals

6.23.2.7

Carbanions Bearing One Phosphorus and Two Sulfur Functions

Deprotonation of bis(ethylsulfanylmethyl) phosphonic acid diethyl ester and of bis(benzenesulfonyl)-diphenyloxoposphinyl methane produces salts 121 and 122, respectively <1982TL499, 1987PS159>. Trifluoromethylsulfonylphenylsulfonyldiphenylphosphinoyl methane reacts with triphenylphosphine to form salt 123, which is protonated on the phosphorus. However, with diphenylphosphinous acid, diethylamideaminophosphine affords phosphonium salt 124, which is protonated on the nitrogen <1977JGU872>.

6.23.2.8

Carbanions Bearing One Nitrogen and Two Sulfur Functions

Bis(phenylsulfonyl)diazomethane is a possible source for the production of an exceptionally electrophilic carbene, bis(phenylsulfonyl)carbene and its chemical properties were studied in the late 1990s. Treatment of bis(phenylsulfonyl)diazomethane with triphenylphosphine yields the stable phosphazine 125 <1963JOC2933>.

6.23.3

CARBON-CENTERED RADICALS BEARING THREE HETEROATOM FUNCTIONS

A few known stable carbon-centered radicals bearing three heteroatom functions have been reviewed <1995COFGT(6)725>. No carbon-centered radicals bearing three heteroatom functions can be regarded as ‘‘stable’’ in that they cannot be isolated and handled. But a few such radicals have significant lifetimes ranging from a few seconds to a few hours in solution <1976ACR13>. These radicals bear silicon, phosphorus, or sulfur substitutents and their increased lifetime can be due to steric factors rather than to electron delocalization.

Br N P N Si +

Cl Cl – Cl

NMe2 S Me2N + NMe2 SiF6–

FO2S – SO2CBr3

111

112

113

110

NO2 _

O O P O

O EtO O P O Li+ O P OEt Cl

Cl

O2N – NO2

116b = NCH2PhMe3

+S(NMe

SO2X

SO2Ph FO2S – SO2F

PhN2+

PhN2+

117a, X = F; 117b, X = CF3

S Ph P Ph

S Ph P Ph

O EtO P OEt

O Ph P Ph

Ph2P – PPh2

Ph2P – PPh2 S S

EtS – SEt

PhO2S – SO2Ph

PhN+2

+NBu

121

122

+

Li

+NBu

4

120

119

PPh2

+ N=NPPh3

2)3

XO2S – SO2X

116a = +NBu4 +

115

114

Br

Br O Br S O O S Br O Br

OEt

118

PPh2 F3CO2S – SO2Ph + HPPh3

4

123

OEt

F3CO2S – SO2Ph + Ph2PNHEt2

PhO2S – SO2Ph

X P OEt SMe

S X P OEt SMe

124

125

126

127

SR

.

Tricoordinated Stabilized Cations, Anions, and Radicals

725

The tris(trimethylsilyl)methyl radical _C(TMS)3 can be generated by decomposition of [(TMS)3C]2Hg <1970CC559> or by reduction of (TMS)3CI <1991CC1608>. This radical is long-lived in solution. A number of carbon radicals bearing three sulfur functions can also be described as persistent, among them C(SCF3), which is generated reversibly from its dimer at room temperature <1979JA6282>, and _C(SCF3)2SC6F5, which is produced from its dimer at 140–190 C <1984T4963>. A number of other radicals bearing three sulfur functions or two sulfur and one silicon functions can be produced by the thermal dissociation of their dimers <1977CB2880>. A series of persistent radicals 126 has been produced by the reaction of the dithioesters 127 with a wide range of radicals R_, including MeS_, Me_, and Ph3Pb_ <1993JA8444>. Since 1995, one or two such radicals have been reported in the literature. The reduction of phosphoryl and thiophosphoryl formates, monothioformates and dithioformates have been studied by means of cyclic voltametry and electron paramagnetic resonance (EPR) spectroscopy data were obtained for these salts <2000JCS(P2)1908, 2002MRC387>. Electron transfer reactions were studied between NO and halotrifluoromethane in the gas phase and the formation of F2CNO radical has been observed <1996JPC10641>.

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Biographical sketch

Marudai Balasubramanian was born in Trichy, India. He obtained his B.Sc. from PEVR College/Madras University, Trichy; his M.Sc. degree at Vivekananda College, Chennai; and his Ph.D. degree in organic chemistry from the Indian Institute of Technology, Chennai, India in 1987. He was briefly a Research Associate at ICI India Ltd., India. His postdoctoral work was conducted with Dr. A. R. Katritzky, Department of Chemistry, University of Florida, Gainesville, FL (1988–1992). During this period, he acquired an in-depth knowledge of various aspects of heterocyclic chemistry and his main research work was concentrated on reactions in hot water. He then worked as a Research Chemist/Research Associate for ten years at Reilly Industries Inc., Indianapolis, IN. His research interests include synthesis of heterocyclic compounds particularly pyridine derivatives, synthesis of intermediates for pharmaceuticals, agrochemicals, performance products, and heterocyclic polymers. In 2002, he joined Pfizer Inc, Ann Arbor, MI as an Information Scientist providing chemistry/patent information to scientists and attorneys.

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Comprehensive Organic Functional Group Transformations 2 ISBN (set): 0-08-044256-0 Volume 6, (ISBN 0-08-044258-7); pp 713–727

Comprehensive Organic Functional Group Transformations, Volume 6 (Synthesis: Carbon with Three or Four Attached Heteroatoms)

Comprehensive Organic Functional Group Transformations, Volume 6 (Synthesis: Carbon with Three or Four Attached Heteroatoms)

Comprehensive Organic Functional Group Transformations,Volume 1 (Synthesis: Carbon with No Attached Heteroatoms)

Comprehensive Organic Functional Group Transformations,Volume 1 (Synthesis: Carbon with No Attached Heteroatoms)

Comprehensive Organic Transformations: A Guide to Functional Group Preparations

Comprehensive Organic Transformations: A Guide to Functional Group Preparations

Comprehensive Organic Transformations. A guide to functional group preparations

Comprehensive Organic Transformations. A guide to functional group preparations

Comprehensive Organic Transformations. A guide to functional group preparations

Comprehensive Organic Transformations. A guide to functional group preparations

Comprehensive Organic Transformations: A Guide to Functional Group Preparations

Comprehensive Organic Transformations: A Guide to Functional Group Preparations

Comprehensive Organic Transformations

Comprehensive Organic Transformations

Comprehensive organic transformations

Comprehensive organic transformations

Comprehensive organic transformations

Comprehensive organic transformations

Organic Functional Group Preparations, Three-Volume Set: Organic Functional Group Preparations

Organic Functional Group Preparations, Three-Volume Set: Organic Functional Group Preparations

Functional group chemistry

Functional group chemistry

Compr. Heterocyclic Chem. III Vol. 9 Six-membered Rings with Three or more Heteroatoms

Compr. Heterocyclic Chem. III Vol. 9 Six-membered Rings with Three or more Heteroatoms

Compr. Heterocyclic Chem. III Vol. 6 Other Five-membered Rings with Three or more Heteroatoms

Compr. Heterocyclic Chem. III Vol. 6 Other Five-membered Rings with Three or more Heteroatoms

Comprehensive Organic Synthesis: Indexes

Comprehensive Organic Synthesis: Indexes

Attached

Functional group chemistry

Functional group chemistry

Geometric Transformations II

Geometric Transformations II

Lie Group Representations II

Lie Group Representations II

Science of Synthesis: Six-membered Hetarenes with Two Identical Heteroatoms v. 16 (Houben-Weyl Methods of Organic Chemistry)

Science of Synthesis: Six-membered Hetarenes with Two Identical Heteroatoms v. 16 (Houben-Weyl Methods of Organic Chemistry)

Organic Synthesis Workbook II

Organic Synthesis Workbook II

Organic synthesis highlights II

Organic synthesis highlights II

Four Winds II Maui

Four Winds II Maui

Functional Analysis II

Functional Analysis II

Density Functional Theory II

Density Functional Theory II

Functional Analysis Vol. II

Functional Analysis Vol. II

Concerning the [unk] Group of Transformations

Concerning the [unk] Group of Transformations

Comprehensive Microsystems, Three-Volume Set

Comprehensive Microsystems, Three-Volume Set

Organic Synthesis Workbook II

Organic Synthesis Workbook II

Organic Chemistry II

Organic Chemistry II

No Strings Attached

No Strings Attached

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