Organophosphorus Chemistry (SPR Organophosphorus Chemistry (RSC)) (Vol 28)

Organophosphorus Chemistry Volume 28

A Specialist Periodical Report

Organophosphorus Chemistry Volume 28 A Review of the Literature Published between July 1995 and June 1996 Senior Reporters D. W. Allen, Sheffield Hallam University, UK B. J. Walker, The QueenS University,Belfast, 'E Reporters C. W. Allen, University of Vermont, USA 0. Dahl, University of Copenhagen, Denmark R. S. Edmundson, formerly of University of Bradford, UK J. A. Grasby, University of Sheffield, UK C. D. Hall, Kings College, London, UK R. N. Slinn, Staffordshire University, Stoke-on-Trent, UK J. C.Tebby, Staffordshire Universiv, Stoke-on-Trent, UK D. M.Williams, University of Sheffield, UK

CHEMISTRY information Services

ISBN 0-85404-3144 ISSN 0306-0713

0The Royal Society of Chemistry 1997 AN rights reserved Apart from any fair dealingfor the purposes of research or private study, or criticism or review as permitted under the terms of the UK Copyright, Designs and Patents Act, 1988, this publication may not be reproduced,stored or transmitted, in any form or by any means, without the prior permission in writing of The Royal Society of Chemistry, or in the case of reprographicreproduction only in accordance with the terms of the licences issued by the Copyright Licencing Agency in the UK,or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the addressprinted on this page.

Published by The Royal Society of Chemistry, Thomas Graham House,Science Park, Milton Road, Cambridge CB4 4WF, UK Typeset by Computape (Pickering) Ltd, Pickering,North Yorkshire, UK Printed and bound by Athenaeum Press Ltd, Gateshead, Tyne and Wear, UK

Introduction

We welcome the return of the Physical Methods chapter, after an absence of eight years, and in particular the return of John Tebby to the team, together with his new co-author, Robert Slinn. We are confident that the compilation of data in this chapter, ranging across virtually the whole of the organophosphorus area, will be valued by our readers. Sadly, we regret that Ron Edmundson and Chris Allen have decided to retire as contributors after this volume. Ron took over authorship of the quinquevalent phosphorus acids chapter in volume 7 of this series, and has contributed every year since then! We are now in volume 28. In subsequent volumes, this chapter will be written by Brian Walker. Chris is a relative newcomer, it is a mere 12 years since he first contributed the phosphazene chapter in volume 16! We estimate that between them they have cited over 8,000 papers in their respective chapters. Our thanks to them both for sustained comprehensive and critical writing over a combined total of 34 years. We are delighted that Dr. J. C. van de Grampel from the University of Groningen has agreed to take over authorship of the phosphazene area. As many of you will know Dr van de Grampel is an established, highly respected researcher in the area and contributed to volume 15 as a joint author of what was then a one-off review of ‘Cyclic and Polymeric Phosphazenes.’ In the areas covered by Chapter 1, (Phosphines and Phosphonium Salts), a significant increase (ca 20%) in the number of publications, compared to last year, is evident. Although it is particularly difficult to identify significant advances, there is clearly a continuing high level of interest, particularly in the chemistry of phosphines and low coordination number phosphorus compounds, reflecting enormous effort world-wide. A number of important review articles have appeared in the area of pentacoordinate and hexaco-ordinate phosphorus chemistry. Robert Holmes has provided an extremely informative comparison of the hypervalency, stereochemistry and reactivity of silicon and phosphorus including the application of the latter to enzyme systems. The coordination chemistry of hydrophosphoranes including the formation of complexes from bicyclic-, tricyclic- and tetracyclic hydrophosphoranes has also been the subject of a comprehensive review with literature coverage to 1995. Numerous metal complexes are mentioned including Rh, Ru, Pd, Co, Fe, Mo,and W and the relevance to asymmetric catalysis is discussed. Neutral six-coordinate compounds of phosphorus, including mono-, di-, tri-, and tetracyclic examples, have also been reviewed. In the phosphorus(V) acids area, there has been continued interest in the preparation of phosphates from elemental phosphorus, and also of compounds derived from the calixarenes. Apart from these, there has been little of real significance in the phosphate field. A much greater interest has been shown in enantio- or diastereo-selectivityin synthesis and reactivity of phosphonates and V

vi

Introduction

phosphinates. Most interest has been concentrated on hydroxyalkyl and aminoalkyl phosphonates, particularly those compounds containing other functions, especially fluorine. Of considerable interest have been studies of stereoselectivity in the alkylation of phosphorus carbanions, and the reactions between the latter and cyclic alkenones. The area of nucleotide and nucleic acid chemistry remains buoyant, including the development of new tervalent phosphorus acid derivatives as reagents for nucleotide synthesis. A major area of interest has been the design of modified internucleotide linkages, including nucleoside phosphonates and analogues thereof. One of the most rapidly developing areas continues to be the application of the MALDI mass spectrometrictechnique to oligonucleotidecharacterisation. Overall levels of innovation this year in the area of ylide chemistry are disappointingly low. All the various forms of phosphorus-based olefination continue to be used widely in synthesis and perhaps the relative paucity of new phosphorus chemistry is a reflection on the extent to which these methods have been developed. One area which does continue to expand, and where there is still considerable potential, is the use of phosphorus-stabilised anions in anantioselective and asymmetric synthesis. Warren’s continuing use of phosphine oxides and Denmark’s excellent contributions to this area are especially worthy of mention. Activity in the phosphazene area continues along the lines noted in the past few years. In the acyclic area a decrease in applications to synthetic organic chemistry and an increase in the use of these materials as ligands has been noted. In cyclophosphazene chemistry the synthetic elegance of dendrimer systems continues to be explored. Other interesting observations involve the change in isomeric selectivity when reactions occur at interfaces and the crown ether effect of oligooxyethylene substituents in promoting reactions of sodium aryloxides, with cyclophosphazenes. Considerable activity in metallacyclic systems, but very little phospha(thia)zene chemistry, has been noted. One of the noteworthy publications, however, is the isolation and characterisation of a cyclothionylphosphazene which is the largest known inorganic heterocycle. In poly(ph0sphazene) chemistry emphasis on membranes, ionic conductors and biomedical systems continues. In the latter, exciting work in slow release agents and microspheres has been published. On the more general matters, it may not be generally appreciated that the sixth edition (1996) of the Heilbron Dictionary of Organic Compounds (and related supplements), published by Chapman and Hall, now includes entries for compounds with P-C bonds, and also some phosphites and phosphates, which initially appeared in the earlier Dictionary of Organophosphorus Compounds, and which have now been up-dated. Useful information on P(II1) compounds and some phosphates can also be found in Chapman and Hall’s Dictionary of Inorganic Compounds D. W. Allen and B. J. Walker

Contents

Chapter 1

Phosphines and Phosphonium Salts By D. W.Allen

1

1

1 1

2 3

4 5 6

Phosphines 1.1 Preparation 1.1.1 From Halogenophosphines and Organometallic Reagents 1.1.2 Preparation of Phosphines from Metallated Phosphines 1.1.3 Preparation of Phosphines by Addition of P-H to Unsaturated Compounds 1.1.4 Preparation of Phosphines by Reduction 1.1.5 Miscellaneous Methods of Preparing Phosphines 1.2 Reactions of Phosphines 1.2.1 Nucleophilic Attack at Carbon 1.2.2 Nucleophilic Attack at Halogen 1.2.3 Nucleophilic Attack at Other Atoms 1.2.4 MiscellaneousReactions of Phosphines Halogenophosphines 2.1 Preparation 2.2 Reactions Phosphine Oxides 3.1 Preparation 3.2 Reactions 3.3 Structural and Physical Aspects 3.4 Phosphine Chalcogenides as Ligands Phosphonium Salts 4.1 Preparation 4.2 Reactions p,-Bonded Phosphorus Compounds Phosphirenes, Phospholes and Phosphinines

5

10 10 11 15 15 16 17 19 23 23 24 25 25 28

30 30 31 31 33 36 43 47

References Chapter 2

1

Peataco-ordinatedand HexacMHdinated Compormds By C. D. Hall

64

1 2

64

Introduction Acyclic Phosphoranes

64

vii

...

Contents

Vlll

3 4 5

Chapter 3

65 67 76

References

78

Tervalent Phosphorus Acid Derivatives By 0. Dahl

80

1 2

Introduction Nucleophilic Reactions 2.1 Attack on Saturated Carbon 2.2 Attack on Unsaturated Carbon 2.3 Attack on Nitrogen, Chalcogen or Halogen Electrophilic Reactions 3.1 Preparation 3.2 Mechanistic Studies 3.3 Use for Nucleotide, Sugar Phosphate, Phospholipid or Phosphoprotein Synthesis 3.4 Miscellaneous Reactions Involving Two-co-ordinate Phosphorus Miscellaneous Reactions

80 80 80 80 82 83 83 87

References

99

3

4 5

Chapter 4

Monocyclic Phosphoranes Bicyclic and Tricyclic Phosphoranes Hexaco-ordinated Phosphorus Compounds

89 95 97 99

Quinquevalent Phosphorus Acids By R S. Edmundron

103

1 2

103 103 103 109 118

3

Introduction Phosphorus Acids and their Derivatives 2.1 Synthesis of Phosphoric Acids and their Derivatives 2.2 Reactions of Phosphoric Acids and their Derivatives Phosphonic and Phosphinic Acids 3.1 Synthesis of Phosphonic and Phosphinic Acids and their Derivatives 3.1.1 Phosphonic and Phosphinic Halides 3.1.2 Alkyl, Cycloalkyl, Aralkyl and Related Acids 3.1.3 Alkenyl, Alkynyl, Aryl, Heteroaryl and Related Acids 3.1.4 Halogenoalkyl and Related Acids 3.1.5 Hydroxyalkyl and Epoxyalkyl Acids 3.1.6 Oxoalkyl Acids 3.1.7 Nitroalkyl Acids 3.1.8 Diazoalkyl and Azidoalkyl Acids 3.1.9 Aminoalkyl and Related Acids 3.1.10 Sulfur and Selenium Containing Compounds

118 118 118 119 122 123 130 132 132 133 143

Contents

ix

4

Chapter 5

3.1.11 Phosphorus-NitrogenBonded Compounds 3.1.12 Phosphorus Containing Ring Systems 3.2 Reactions of Phosphonic and Phosphinic Acids and their Derivatives Structure

147 157

References

160

Nucleotides and Nucleic Acids By J. A. Grasby and D. M. Williams

170

1 2

170 170 170 170 180 185 188 191 191 195

3 4

5 6

7

Introduction Mononucleotides 2.1 Nucleoside Acyclic Phosphates 2.1.1 MononucleosidePhosphate Derivatives 2.1.2 PolynucleosideMonophosphates 2.2 Nucleoside Cyclic Phosphates Nucleoside Polyphosphates Oligo- and Poly-nucleotides 4.1 DNA Synthesis 4.2 RNA Synthesis 4.3 The Synthesis of Modified Oligodeoxynucleotides and Modified Oligoribonucleotides 4.3.1 OligonucleotidesContaining Modified Phosphodiester Linkages 4.3.2 OligonucleotidesContaining Modified Sugars 4.3.3 OligonucleotidesContaining Modified Bases Linkers Interactions and Reactions of Nucleic Acids with Small Molecules Determination of Nucleic Acid Structures References

Chapter 6

143 143

195 195 207 209 215 225 226 228

Ylides and Related Compounds By B. J. Walker

237

1 2

237 237 237 242 242 244 246

3 4

Introduction Methylenephosphoranes 2.1 Preparation and Structure 2.2 Reactions of Methylenephosphoranes 2.2.1 Aldehydes 2.2.2 Ketones 2.2.3 Miscellaneous Reactions The Structure and Reactions of Phosphine Oxide Anions The Structure and Reactions of Phosphonate Anions

252

259

Contents

X

5

Chapter 7

Chapter 8

Selected Applications in Synthesis 5.1 Amino Acids and Peptides 5.2 Carbohydrates 5.3 Carotenoids, Retenoids, Pheromones and Polyenes 5.4 Leukotrienes, Prostaglandins and Related Compounds 5.5 Macrolides and Related Compounds 5.6 Nitrogen and Oxygen Heterocycles 5.7 Tetrathiafulvalene Derivatives and Related Compounds 5.8 Miscellaneous Reactions

267 267 269 271

References

280

Phcwphazeaes By C. W.Allen

285

273 274 275 277 278

Introduction Acyclic Phosphazenes Cyclopho sphazenes Mixed Main Group - Phosphazene Ring Systems Including Cyclophospha(thia)zenes Metallocyclic Phosphazenes Poly(phosphazenes) Crystal Structures of Phosphazenes and Related Compounds

285 285 29 1

References

318

297 299 302 308

Physical Methods By R N.Slinn and J. C. Tebby

328

1

328 328 330 330 330 331 331 339 340 340 341 342

2

Theoretical Studies 1.1 Studies Based on Molecular Orbital Theory 1.2 Studies Based on Molecular Mechanics Theory Nuclear Magnetic Resonance Spectroscopy 2.1 Biological and Analytical Applications 2.2 Chemical Shifts and Shielding Effects 2.2.1 Phosphorus-31 NMR 2.2.2 Selenium-77NMR 2.2.3 Carbon-13 NMR 2.2.4 Hydrogen-1 NMR 2.2.5 Other NucleYMdtinuclear NMR 2.3 Restricted Rotation and Pseudorotation 2.4 Studies of Equilibria, Configuration and Conformation

342

Conten rs

xi

3 4 5

6

7

8 9

10

11

Author Index

2.5 Other Studies 2.6 Spin-Spin Couplings Electron Spin Resonance Vibrational and Rotational Spectroscopy Electronic Spectroscopy 5.1 Absorption Spectroscopy 5.2 Fluorescence Spectroscopy X-ray Diffraction (XRD) 6.1 Two-coordinate Compounds 6.2 Three-coordinate Compounds 6.3 Four-coordinate Compounds 6.4 Five- and Six-coordinate Compounds Electrochemical Methods 7.1 Dipole Moments 7.2 Cyclic Voltammetry and Polarography 7.3 Ion-selectiveand Potentiometric methods Acidities, Basicities and Thermochemistry Mass Spectrometry Chromatography and ‘Hyphenated’ Techniques 10.1 G a s Chromatography and Gas ChromatographyMass Spectroscopy (GC-MS) 10.2 Liquid Chromatography 10.2.1 High Performance Liquid Chromatography and LC-MS 10.2.2 Ion Chromatography 10.2.3 Thin Layer Chromatography 10.3 Capillary Electrophoresis and Micellar Electrokinetic Chromatography Kinetics

344 344 345 346 346 346 346 347 347 347 347 349 350 350 350 351 351 351 352

References

353

352 352 352 352 352 353 353

359

Abbreviations

AIBN CIDNP CNDO CP DAD DBN DBU DCC DIOP DMF DMSO DMTr EDTA EHT ENU FID GLC-MS HMPT HPLC IR LFER MIND0 MMTr MO MS-Cl MS-nt MS-tet NBS NQR Pe PPA SCF TBDMS TDAP TFAA TfO THF Thf ThP

bisazoisobutyronitrile Chemically Induced Dynamic Nuclear Polarization Complete Neglect of Differential Overlap cyclopentadienyl diethyl azodicarboxylate 1,5-diazabicyclo[4.3.O]non-5-ene 1,5-diazabicyclo[5.4.0]undec-5-ene dicyclohexylcarbodi-imide [(2,2-dimethyl-1,3-dioxolan-4,5-diyl)bis-(methylene)~bis(diph~nylphosphine) dimethylformamide dimethyl sulphoxide 4,4'-dimethoxytrityl ethylenediaminetet ra-acetic acid Extended Huckel Treatment N-nitrosourea Free Induction Decay gas liquid chromatography-mass spectrometry hexamethylphosphortriamide high-performance liquid chromatography infrared Linear Free-Energy Relationship Modified Intermediate Neglect of Differential Overlap 4-monomethoxytrityl Molecular Orbital mesitylenesulfonylchloride mesitylenesulfonyl-3-nitro1,2,4-triazole mesitylenesulfonyltetrazole N-bromosuccinimide nuclear quadrupole resonance photoelectron polyphosphoric acid Self-consistent Field t-butyldimethylsilyl tris(diethy1amino)phosphine trifuluoroacetic acid trifluoromethanesulfonic anhydride tetrahydrofuran 2-tetrahydrofuranyl 2-tetrahydropyranyl xii

...

Abbreviations

TIPS TLC TPS-Cl TPS-nt TPS-tet TsOH

uv

Xlll

tetraisopropyldisiloxanyl thin-layer chromatography tri-isopropylbenzenesulfonylchloride tri-isopropylbenzenesulfonyl-3-butri1,2,4-triazole tri-isopropylbenzenesulfonyltetrazole toluene-p-sulfonic acid ultraviolet

1 Phosphines and Phosphonium Salts BY D.W. ALLEN

1

Phosphines

1.1 Preparation 1.1.1 From Halogenophosphines and Organometallic Reagents. - The application of organolithium reagents has once again dominated this route to phosphines. An improved route to tri-2-furylphosphine (1) is provided by treating furan with butyllithium, followed by cerium trichloride, and then with phosphorus trichloride. Difficulties continue in attempts to prepare the pyridylphosphine (2) by the lithiation of 2,6-dibromopyridine and subsequent treatment with phosphorus trichloride. Terpyridyl systems are the main products, rather than the desired phosphine.2 A range of functionalised quinolinylmethylphosphines (3) has been ~ r e p a r e d .The ~ reaction of 2,2'-dilithiobiphenyl with chlorodiphenylphosphine has been revisited, and the anomalous formation of 5-phenyldibenzophosphole and triphenylphosphine, rather than the diphosphinobiphenyl (4), confirmed. The latter can, however, be prepared by Ullman coupling of oiodophenyldiphenylphosphine oxide, followed by reduction with trichl~rosilane.~ A study of the energy barrier to axial torsion in the biphenyl (4) reveals that, even if it could be resolved into pure enantiomers, rapid racemisation would occur at temperatures greater than 25 0C.5 Direct metallation at carbon, followed by treatment with chlorodiphenylphosphine, has been used to prepare a range of new diphosphines, e.g., (5)6, (6)', and (7)8,the latter system having been resolved

q-p RO

PPh2

PhpP

(3) = ButMepSi,H or OAc

PPh2 (4)

QqPPh,

PhpP

PPhp

(5) R = Hor Me X = Mesi, M e C or S

(6)

1

( 7 ) R = M*NCH2 or H

2

Organophosphorus Chemistry

ph?4ph

into chiral forms. Diphosphines bearing other functional groups, some of which are chiral, e.g., (8)9, (9)*O, and (lo)]], have also been prepared. A route to the benzenetricarbonylchromium-baseddiphosphine (11) has also been developed.l2 Coordination-directed metallation of hydrazone systems, followed by treatment with chlorodiphenylphosphine,provides a route to the functionalised phosphines (l2)I3 and (13).14 The latter can be easily converted into the chiral aphosphinoketones (14).14

R' L

P

I

R

9

k2

(14)

Metallation of 1,3,5-tricyanocyclohexane,followed by treatment with chlorodiphenylphosphine results in the formation of the cis-triphosphine (19,in which all the phosphino centres are available for coordination in a 'facial' manner." The organolithium-halogenophosphine route has been applied extensively in the synthesis of ferrocenyl phosphines. New approaches for asymmetric synthesis of

I : Phosphines and Phosphonium Salts

3

NcwzN &PPh2

i

PPh2

@PPh2

CN

(16)

(15)

chiral ferrocenylphosphines have been reviewed.16 An improved route to the ferrocenyldiphosphine (16) has been described.I7 Lithiation of the ferrocene system ortho to a chiral group containing an appropriate donor atom has been applied in the synthesis of a considerable number of new systems. Four groups' 8-21 have described the use of chiral oxazolinyl substituents at ferrocene for this purpose, resulting in a range of chiral oxazolinylferrocenylphosphine hybrid ligands, e.g., (17)20 and (18).21 Among other chiral systems prepared in a similar manner are the ferrocenophanes (19),22923the chiral aminoalkylferrocenylphosphines, e.g., (20),24925 and the chiral dioxolanyl system (21), a precursor of the aldehydo-phosphine (22), which, with ethylenediamine, yields a tetradentate

&>: I

N

Fe

Fe

(17) R = Pr'or Me

PPh2 (18)

R = Pr'orBu'

PN I

PPh2

k

(19) R = H or PPh2

= Et or Bu R2 = H or PPh2

(20)R'

bis(iminophosphine), having planar chirality.26A similar approach has been used in the synthesis of other phosphinoferrocenes having planar chirality.27Enantioselective ortholithiation of several aminomethylferrocenes with butyllithium in the presence of a chiral diamine, followed by treatment with chlorodiphenylphosphine, has given a series of ferrocenylphosphines having planar chirality, e.g.,

4

Organophosphorus Chemistry

eCHo I

Fe

(23)

(24)

(25)

(23).28The ortholithiation route has also been used in the synthesis of the related ruthenocenyl system (24).29 Metallation of ferrocenecarboxaldehyde with the lithium derivative of monomethylpiperazine, followed by treatment with chlorodiphenylphosphine, provides a one-pot route to the 1,l'-disubstituted system (25) in moderate yield.30 A series of phosphaferrocenophanes (26) has been prepared by the reaction of 1,1'-dilithioferroceneswith halogenophosphines. On heating, ring-opening polymerisation occurs to give the polymeric phosphines (27).31

Rk

4vR2

R'

(26) R1 = H,Bu or SiMe3 R2 = Ph or CI

Both alkynyl-lithium and alkynyl-Grignard reagents have been used in the synthesis of sterically protected diethynylphosphines and dibutadiynylphosphines, e.g., (28).32 The reaction of chlorodiethylphosphine with the reagent BrMgC = CMgBr has given the diphosphinoacetylene (29).33 Cyclohexylmagnesium bromide has been used in the synthesis of the chiral diphosphine (30) from tran~-l,2-dichlorophosphinocyclopentane.~ The Grignard route has also been applied in the synthesis of a series of new chiral phosphines having binding sites of different hardness, e.g., (31).35 In a rare example of the application of other organometallic reagents in

Ar-PfC=C-C=C-SiMe3)2

(28) Ar = 2,4,6-But3C~H2

qPh 9 oc*

CY2P

PCY2

1: Phosphines and Phosphonium Salts

5

phosphine synthesis, the zirconacyclopentanes (32) have been shown to react with dichloro- and monochloro-phosphines to give the heterocyclic phosphines (33) and the diphosphines (34), re~pectively.~~ 1.1.2 Preparation of Phosphinesfrom Metallated Phosphines. - Both lithium- and sodium-bis(o-methoxypheny1)phosphideshave been isolated as unsolvated solids, the former from the reaction of bis(u-methoxypheny1)phosphine with butyllithium, and the latter from treatment of tris(o-methoxypheny1)phosphine with sodium in liquid ammonia. Both reagents decompose in solution in THF over several days.37Structural and N M R studies of the dilithiodiphosphides (35) have been reported.38 The first structural characterisation of a dilithiophosphandiide, in the form of a complex with a fluorosilane, has been achieved.39 Organophosphide anions stabilised by coordination to borane have synthetic advantages over the free organophosphides in being only mildly basic. Such reagents have been used to convert chiral ditosylates to chiral diphosphineLi

R2

PR'

Li (35) R' = H, Ph, or SiMe3 R2 = H or Me

(36) R = Ph or Cy n = 1 or2

borane complexes, from which the free c h i d diphosphines, e.g., (36), are easily liberated.40 Such reagents have also found use in the synthesis of phosphinofullerenes."l The triarylphosphine (37) undergoes the expected cleavage of an aryl-phosphorus bond on treatment with lithium metal in THF,and treatment of the resulting diarylphosphide reagent with a chiral ditosylate has given the chiral diphosphine (38). This has been shown to undergo sulfonation at the terminal benzene rings to give a chiral, water-soluble diphosphine, which also shows surface active proper tie^.^^ A related chiral ditosylate-lithium diphenylphosphide route has been employed in the synthesis of the chiral diphosphine (39).43 Similar

6

Organophosphorus Chemistry

H

H (41) R' = H, Me or Ph

(42)M

=

Fe or Ru

R2 = CH20H or o-or pC6H40H

routes have been used for the synthesis of the new chiral systems (40)44,(41)"' and (42).46 Lithiophosphide reagents have also found application in the synthesis of a range of chiral phosphines based on carbohydrate systems, e.g., (43),47*48the key step being nucleophilic ring-opening of epoxide derivatives with lithium diphenylphosphide. A lithiophosphide-tosylate route has been used in the synthesis of the carbohydrate-based diphosphine (44).49 Conjugate addition of lithium diphenylphosphide to a$-unsaturated carboxylic esters is the key step in the synthesis of p-phosphinocarboxylic acids, e.g., (45).50*51The ferrocenylborylphosphinesystem (46), in which there are 'through space' intramolecular boron-phosphorus inter-

(43)

(44)R = Me or PhCH2

(46) R = Me or Br

actions, has been prepared by the reaction of lithium diphenylphosphide with dibromodiborylferrocne precursor^.^^ Treatment of the cyclopropenium salt (47) with lithium diphenylphosphideresults in the formation of the cyclopropenylphosphine (48), which does not undergo thermal or photochemical rearrangement or ring-~pening.~~ A range of new amphiphilic phosphines, e.g., (49), containing polyether chains, has been prepared via the use of phosphide reagents obtained by lithium-induced cleavage of a phenyl group from either octyldiphenylphosphine or isopentyldiphenylphosphine, and their subsequent reactions with

1: Phosphines and Phosphonium Salts

7

R2 = H or Me OEt

I B ~ P -C= C H ~ I R

M ;e ;$; (511

(50)

(53) R = 1-naphthyl or mxylyl

(52) R = ptolyl or xylyl

(54) R = H o r M e

chloroalkyl ethers.% The phosphide reagent derived from the secondary phosphine (50, R=H) has been alkylated to give the tertiary phosphines (50; R=PhCH2 or M ~ O C H Z )Several . ~ ~ groups have reported lithiophosphide routes to tripodal polydentate mixed donor phosphine ligands, e.g., (51),56 (52),57(53),58 and (54).59 Lithiophosphide reagents have also been employed in the synthesis of a range of pyridylphosphines, e.g., (55),60 (56),61 and (57).62 The chiral phosphinoaryloxazolines (58) have been obtained by nucleophilic displacement of

qPPh2 ad" Q PPh2

EPPh2 Me'

(58) R' = H, alkyl or Ph R2 = H or Me

fluorine from the related o-fluoroaryl systems, using lithium diarylphosphide reagents.63Dilithiodiphosphide reagents are key intermediates in the synthesis of the heterocyclic systems (59)64 and (60),65 and a range of macrocyclic diphosphines, e.g., (61).* The difunctional reagent, dilithiumphenylphosphide, has also been used in heterocyclic synthesis. With 1,3-dichloropropane or 1,2dichloroethane, the simple phosphetane (62) and phosphirane (63), respectively, result, both of which can be isolated by vacuum distillation. The phosphetane rapidly polymerises in the neat state, but is stable in solution in benzene, in which it has a remarkably low field 31P NMR shift (13.9 ppm). In contrast, the phosphirane exhibits an even more remarkable high-field shift ( -236 ~ p r n ) . ~ ~

8

Organophosphorus Chemistry

Ph

G'

AP

0 'F-Jf-Y;: ,

D

Ph

(59)

cb,

Ph

(62)

3:: Ph

H

H (60)

\p/I Ph

N- (CHdn-

N-(CHdn-%

d

3 Ph

0

qp

(61) n = 2 o r 3

Ph'

(63)

(64)

The selenium-phosphorus system (a), isolated as the related phosphine oxide, has been obtained from the reaction of dilithiurnphenylphosphide with bis(obromomethylphenyl)selenide.68 This phosphide reagent has also been employed in the synthesis of a range of six-membered P2B4 heterocycle^.^^ Dilithioorganophosphide reagents have also been used in the synthesis of the phosphines (65), albeit in lowish yield.70 It has been shown that whereas methyl fluoroformate reacts with an equimolar quantity of lithiumbis(trimethylsily1)phosphide to give an inseparable mixture of tris(methoxycarbony1)phosphine (66) and tris(trimethylsilyl)phosphine,colourless crystals of a lithium bis(methoxycarbony1)phosphide-dimethoxyethane solvate are obtained in high yield from the reaction of the fluoroformate ester with lithium phosphide in a 2:3 molar ratio. Protonation of the bis(methoxycarbony1)phosphide yields the secondary phosphine (67), which, unlike other diacylphosphines, does not show the presence of an en01 tautomer even in non-polar solvents.71Lithiumbis(diorganophosphino)phosphide reagents have been used in the synthesis of phosphino-phosphinidene-phosphoranes, R~P-P=P(R)Bu'~, involving two-, three-, and four-coordinate, directly bonded phosphorus a t o m ~ . ~A* wide * ~ ~range of alkali metal phosphide reagents has been utilised in the synthesis of silylphosphine systems, including an improved preparation of tris(trimethyl~ilyl)heptaphosphine,~~ and a variety of heterocyclic Si-P compound^.^'-^^ The phospholenes (68) have been obtained from the reactions of the l-lithiophospholenide reagent with group 14 halides.79 Me R1-P(CH2CH20R2)2

(67) R1 = P* or But R2 = Me or Et

P(C@Me)3 (66)

HP(C02Me)2 (67)

Me

kj I

EMe3 (68) E = Si, Ge or Sn

Applications of sodio- and potassio-organophosphidereagents also continue to appear. A mixed sodio-potassio-diphenylphosphidehas been used in the synthesis of the chiral systems (69).80Interest has also continued in exploring SRNlprocesses involving metallophosphide reagents in liquid ammonia, some of which are

I : Phosphines and Phosphonium Salts

9

I

.PPh2

(69)

R R = H or 2-pyridyl

Fe

Me2P

(70)

(73) n = O o r l

(72)

synthetically u s e f ~ l . ~Potassiophosphide l-~~ reagents have been applied in the synthesis of the quinolylphosphine (70):4 the ferrocenyl ligand (71),85and the water-soluble triphosphine (72).86 The heterocyclic systems (73)have been isolated from the reactions of 1,4- and 1,5-dihaloalkanes with the phosphide reagent generated from red phosphorus and potassium hydroxide in aqueous dioxan, in the presence of phase-transfer catalyst^.^' Dipotassiodiphosphide reagents have been used in the synthesis of heterocyclic P-Sn and P-B ~ y s t e m s .Alkylation ~ ~ . ~ ~ of 1,2bis(phosphino)benzene(in the form of a copper(1) complex) can be achieved in the presence of potassium t-butoxide and alkyl halides, enabling the synthesis of, e.g., the heterocyclic systems (74) and (79, and the bis(secondary)phosphine(76).90

uPHM PHMe

(74)

n = l or2 (75)

Once again, there has been strong interest in the synthesis and characterisation of organophosphido derivatives of other main group elements, notably a l ~ m i n i u m , 9 g~ *a ~l l~i ~ m , ~ indium,w ~ - ~ ~ and germanium, tin, and lead.loo fn addition, organophosphido derivatives of lanthanide,l o 1 p 1 0 2 actinide,lo3 and dblock transition elements,104-1 l 3 have been described. Interest also continues in the chemistry of phosphines metallated at an adjacent carbon. The use of phosphinomethanide reagents in the synthesis of novel heteroorganic compounds has been reviewed, l4 and further examples described. l5 The borane adduct of methyldiphenylphosphine can be metallated at

Organophosphorus Chemistry

10

the methyl group using sec-butyllithium, to generate the borane-protected reagent (77), the key intermediate in the synthesis of the tripod ligands (78). * I6 Arylphosphines bearing organosilyl substituents, e.g., (79),have been obtained via the intermediacy of C-metallated systems. l7 A further study of the products of iodineoxidation of the bis(dipheny1phosphino)methanide ion has been reported.11*

(78) RE = MeSi or BuSn

(79)

1.1.3 Preparation of Phosphines by Addition of P-H to Unsaturated Compoundr. -

This route has not received much attention over the past year. A stereoselective synthesis of tris(2-styry1)phosphine is offered by the addition of phosphine to phenylacetylene in a superbasic system (HMPA-H20-KOH).ll9 In a similar vein, the reaction of phosphine with styrene and a-methylstyrene in a superbasic medium (DMSO-KOH)provides a route to the primary phosphines, (2phenylethy1)phosphine and (2-methyl-2-phenylethyl)phosphine,respectively.120 Transition metal phosphine complexes have been shown to catalyse the a-hydroxylation, p-cyanoethylation, and P-alkoxycarbonylethylation of phosphine.121 Addition of primary phosphines to acrylic esters has been used for the synthesis of the phosphines (80).70 A similar addition of diphenylphosphine to acrylic esters and amides has given a series of hydrophilic phosphines (81).122 The bis(phosphorinany1)ethane (82) is formed in the photochemical addition of lY2-bis(phosphino)ethaneto 1,4-pentadiene.64

(80) R' = Ph or But R2 = Me or Et

(81) R = OH, OMe, OCH2CH2Nhe3 I-, or NHCMe2CH2S03-

(82)

1.1.4 Preparation of Phosphmes by Reduction. - The reduction of phosphine

oxides in the final stage of phosphine synthesis remains a common strategy, with silane reagents often being used. Trichlorosilane has found application in the synthesis of the axially chiral systems (83),123 (84),lZ4 (85),125 the chiral

Ph

SH PPh2

I : Phosphines and Phosphonim Salts

11

Ar2P

I

I

Fe

Ar2P

I I

Fe

Men/p+

(87) Ar = Ph, pMe0C6Hs, pCICsH4, ptolyl, or 2-fury1

diphosphine (86), 126 and the diphosphinobiferrocenyls (87).12’ This reagent has also found use in the synthesis of the phospholene (88), whereas phenylsilane was the reagent of choice for the isomeric system (89). Following protection of (88) and (89) with borane, attempts have been made to achieve ring-expansion on treatment with chlorocarbenes.12* Phenylsilane has also found use in the synthesis of the poly(ary1ene-ether-triarylphosphine) system (90). 129 A mild and practical synthesis of secondary P-ethynylphosphines (91) is provided by

R’C=CPHR~ (91) R1 t H or Ph R2 = Pr’, But, Et or Ph

reduction of the easily available oxide precursors with phenylsilane for the P-alkyl systems, and a mixture of phenylsilane and phenyltrichlorosilane for the P-phenyl system.130 Various hydrosilane reagents have also been used in the synthesis of the heterocyclic systems (92).131 Full details have now appeared of the synthesis of the secondary phosphine (93), isolated as one resolved diastereoisomeric form.I3* The chiral bis(primary)phosphine (94) has been obtained by the reduction of a diastereoisomerically pure trans-l,2-cyclopentanobisphosphonite ester using lithium aluminium hydride. 33 Aluminium hydride has been employed in the synthesis of a range of arylphosphinefunctionalised silasesquioxide materials, precursors for the synthesis of organometallic-functionalisedsilica gel. 34

(92) R = Me or Ph

(93)

(94)

1.1.5 Miscellaneous Methodr of Preparing Phosphines. - Transformation of functional groups present in alkyl- and aryl-phosphines has been widely employed in the synthesis of new systems. Further examples of azine formation

12

Organophosphorus Chemivtry

from the phosphinohydrazone (95) have been reported, leading to the synthesis of new mixed donor l i g a n d ~ . l ~ ~Treatment -l~' of the phospholene (96) with dicyclopentadienylzirconium(chloro)hydride, followed by a phosphenium salt, results in ring-opening with the formation of the unsaturated 1,l-diphosphines (97).138The reactions of the OH group of the enantiomerically pure cis- or transphosphino-alcohol (98) with atropisomeric chlorophosphites have given a series of chiral phosphinocycloalkylphosphitoligands, e.g., (99).139

R2P-P-CH2CH2CH I Ph

=CH2

ph2v b

(97) R = NPr$ or NCy2

2

-

O

(98)

Hydroxymethyldiphenylphosphine has been used in the final stage of the synthesis of a dendrimer molecule having 3072 diphenylphosphino groups at its surface.140 Carbodiimide-promoted formation of amides is the key step in the convmsion of diphenylacetic acid and p-diphenylphosphinobenzoic acid to a range of amidoakyl- and amidoaryl-phosphines, e.g., In a similar vein, @iiphenylphosphinopropanoic acid has been coupled via the carboxylic acid group to a dipeptide to provide the tetradentate PN2S hybrid ligand (101).14*A synthesis of the dicyclohexylphosphinoamino acid (102), has been described, starting from dicyclohexylphosphine.143 A palladium-catalysed synthesis of the phosphinoarylamino acid derivatives (103) has been developed from the reaction

H Cy2p/YC@H

ph2p*

NHR pph2

I : Phosphines and Phosphonium Salts

13

(105)

of diphenylphosphine with amino acid aryltriflates derived from tyrosine and hydroxyphenylglycine.144 The chiral diphosphine (104) has been coupled to polyacrylic acid via DCC chemistry, and the resulting polymer converted into a water-soluble sodium salt.145The ethoxysilylarylphosphine (105), in the form of a bis(phosphine)Ni(O) complex, becomes bonded to a silica surface via only one phosphine unit simply by heating with silica in toluene solution.146In addition to the study of such surface-bound systems by solid state NMR techniques, it has been shown that useful information can also be obtained by conventional NMR techniques on suspensions of such materials in various NMR solvent^.'^' Phosphine-functionalised surfaces have also been obtained via the reactions of y-diphenylphosphinopropanolswith aminosilane-functionalised glass, quartz or silicon.148 The use of p-diphenylphosphinobenzaldehydein the standard synthesis of tetraarylporphyrins on heating an aromatic aldehyde with pyrrole in propionic

14

Organophosphorus Chemistry

acid has given the tetraphosphinoporphyrin (106) from which the tetra-oxide, -sulfide, and various metal complexes have been prepared. In addition, quaternization with p-xylylene dibromide has given a water-soluble octakis(phosphonio)porphyrin double decker system with a cage structure, this being the first example of an ionic, vertically-stacked porphyrin.149 Metal ion template-assisted cyclisation reactions of 1,3-bis[(2-aminophenyl)phenylphosphino]-propaneare crucial steps in the synthesis of a range of chiral macrocyclic diphosphines, e.g., (1O7).I5O Oxidative coupling of C-lithiated aryldimethylphosphines (protected at phosphorus via sulfur or borane) has provided a route to the C2-symmetricP-chiral

bPh2

Ph2g

(110) R’ = Ph or But R2 = Ph, But or Me

diphosphines, (108).151A route to the multidentate, mixed donor phosphine system (109) has been developed.I5*A range of cyclocarbatetraphosphines (110) has been obtained from the reactions of cyclopolyphosphines with various methylenebis(ph0sphine) derivatives.153 Monoquaternization of the bicyclic diphosphines (11l), followed by cleavage of the P-P bond with an organolithium or Grignard reagent, provides a stereoselective route to medium ring cis-1, n-dialkyl-1,n-diphosphacycloalkanes(1 12).’” The same group has also developed a route to the bicyclic system (113).155The triphosphorus macrocycle (114) can be liberated from its complex with molybdenum (the form in which it is isolated from a template-modified synthesis) by oxidation of the metal with a halogen and subsequent decomposition with aqueous base. R

The synthesis of atropisomeric biphenylyldiphosphines has been reviewed. 15’ The ferrocenyldiphosphine (115) has been prepared by treatment of 1,l‘-dilithioferrocene with an aryl methylphenylphosphinite, and isolated in the form of two diastereoisomers which are separable by recrystallisation from ethanol.15* Metallation of mono- and di-(tetramethylcyclopentadienyl)phosphines, followed by treatment with iron(I1) chloride, provides a route to the ferrocenyl systems (116)

1: Phosphines and Phosphonium Salts

15 Me

I

R

Me

Me

Ph

&PPh2

@COOH

and (117; R = Me).lS9 Nucleophilic ring-opening of (117; R = H) with phenyllithium, followed by treatment with carbon dioxide and acidification leads to the phosphinoferrocenecarboxylicacid (1 18).160 A related ring-opening with 2lithio-a-N,N-dimethyI)aminoethylbenzene,followed by protonation, has given the chiral aminophosphinoferrone (1 19).161The side-chain reactivity of appropriate ferrocenylmethyl substrates has been utilised in the synthesis of a range of new chiral ferrocenylphosphines,162-16s e.g., (120). 165 A quantitative yield of the acylphosphine (121) has been obtained from the reaction of l-bromo-l-cyclopropanecarboxylic acid chloride with tris(trimethylsily1)phosphine in benzene or toluene at low temperatures. The reactions of diphenyltrimethylsilylphosphine with aldehydes have given a series of siloxymethylphosphines (1 22). 16' Tris(trimethylstanny1)phosphine has been used to introduce the trimethylstannyl substituent into the triphosphacyclopropane (123) v i a its reaction with the related monochlorotriphosphacyclopropane.16* SnMe3

P(SiMe3)p

Ph2PCH(R)OSiMe3

P /\ Bu'P-PBu'

Br

0

( 122)

(123)

(121)

1.2 Reactions of Phosphines 1.2.1 Nucleophilic Attack at Carbon. - Rate constants for the forward and reverse formation of the tributylphosphine - carbon disulfide adduct, Bu3P+-

CS2-, have been determined in a range of solvents. The forward reaction constant shows little variation with solvent, whereas the reverse reaction constant

16

Organophosphorus Chemistry

varies widely. The reactions of the adduct with maleic anhydride and Nphenylmaleimide have also been studied, and shown to be solvent dependent. Thus, e.g., with maleic anhydride in ether, the phosphoranylidenesuccinic anhydride (124) is the major product, whereas in acetonitrile the dithiaperhydropentalenedione system (125) predominates.169 Phosphines, and other trivalent phosphorus nucleophiles, add irreversibly to the carbon-carbon double bond of 2-cyanoacrylates to form zwitterions, which, unless trapped by other reagents, e.g., phenylisocyanate, initiate polymerisation.170 Initial nucleophilic addition of tricyclohexylphosphine to the triple bond of acetylenic esters and ketones is the key step in catalysis by the phosphine of alkyne cyclotrimerisation and addition to [60] - f ~ l l e r e n e . ' ~ ~Phosphines .'~~ have also been shown to catalyse the umpolung addition of nucleophiles to 2,3-butadienoatesYgiving inverse addition y(-adducts), regioselectively.173 Interest has continued in studies of the addition of phosphines to alkenes coordinated to metals.174J75 Zwitterionic cycloadducts, e.g., (126), have been obtained from the reactions of

Z-1,2-borylphosphinoalkeneswith carbonyl compounds and ketenimines.176*177 Two reports of the reactions of (trimethylsily1)phosphines with a,&unsaturated carbonyl compounds have appeared. These reactions usually lead to transfer of a trimethylsilyl group from phosphorus to oxygen, presumably via the intermediacy of a phosphonioenolate betaine, the initial product of nucleophilic attack by the phosphine at the P-carbon.178*179 However, other pathways also arise in the reactions of sterically crowded organotrimethylsilylphosphines, and transfer of a trimethylsilyl group from phosphorus to the a-carbon has been observed.179 1.2.2 Nucleophilic Attack at Halogen. - A series of adducts of tertiary phosphines with iodine has been isolated from their reactions in ether solution. The predominant solid state structure is the established molecular 'spoke', R3P-I-I; however, in some cases, ionic structures have also been characterised.180 The reactions of 4-unsubstituted-5-(4H)-oxazoloneswith tertiary phosphine-halogen reagents, e.g., Ph3P-Br2,Bu3P-Br2,Ph3P-CC4, or Ph3P-CBr4,in the presence of triethylamine in dichloromethane at room temperature, lead to the isolation of the 4-phosphoranylidene-5(4H)-oxazolones (127).**l The triphenylphosphinecarbon tetrachloride system has been used for the dichloromethylenation of phthalimides,lS2 and for the synthesis of saturated seven-membered ring cycloacetals via a diastereoselective intramolecular cyclization process.lS3 Acyl halides have been generated in high yields under mild conditions from the reactions of the parent carboxylic acids with the appropriate N-chloro- or Nbromo-succinimide. The combination of triphenylphosphine with cyanogen

I : Phosphines and Phosphonium Salts

17

0

(127) R' = Bu or Ph R2 = Me, But, P+or Ph

bromide also provides a reagent for the conversion of carboxylic acids to the related acyl bromides.la A route to secondary or tertiary amines is provided by the treatment of triphenylphosphine with N-bromosuccinimide in the presence of a primary alcohol at low temperatures, followed by addition of a primary or secondary amine and heating for an The triphenylphosphine - carbon tetrabromide combination has found use for the selective cleavage of ketals and acetals under neutral, anhydrous conditions at room temperature.186A route to quinolines is provided by the cyclisation of P-arylaminoacrylamides in the presence of the triphenylphosphine - hexachloroethane - triethylamine combination. 1.2.3 Nucleuphilic Attack at Other Atoms. - Trifluoromethanesulfonyloxyboron derivatives of tricyclohexylphosphine-borane have been prepared. Two enantiomerically pure borane complexes of chiral dihydrobenzazaphosphole systems, e.g., (128), have been structurally ~haracterised.'~~ The synthesis of phosphinoboranes bearing an L-menthyloxy group is a key strategy in the synthesis of chiral phosphines, e.g., (129).190J91Treatment of the phosphines (1 30) with the chloroborane-dimethylsulfideadduct results in the formation of the novel PBS heterocyclic system (1 3 1).192

(130) R1 = R2 = Ph or Cy R' = Ph; R2 = eanisyl R' = Phi R2 = & v ~ S & H ~

Further studies have been reported of the intramolecular transfer of oxygen from nitrogen or sulfur to phosphorus in odiarylphosphino-nitrones, -acetylhydroxylamines, and -sulfoxides. Thus,e.g., the phospho-nitrone (1 32) rearranges on heating in toluene for a prolonged period to form the iminophosphine oxide

18

Organophosphorus Chemistry

(133), via a six-membered PON intermediate. However, a single general mechanism for the reactions of all of the above classes of compound could not be established.193 Photo-oxidation of triphenylphosphine, and also de-oxygenation of triphenylphosphine oxide, have been observed at the surface of illuminated titanium dioxide, in an organic solvent containing triethylamine, which acts as a sacrificial electron donor. lg4 Enantioselective oxidation of racemic phosphines has been achieved using chiral oxoruthenium(V1) porphyrin~.'~~ Nucleophilic attack of triphenylphosphine at the sulfur atom of thiopheneendoperoxides is the key step in their conversion to furan derivatives.lg6Although the nucleophilicity of phosphorus in tetra-t-butyltetraphosphacubaneis reduced, possibly owing to the participation of the lone pairs in the phosphorus carbon skeleton, it is possible to achieve stepwise oxidation of all four phosphorus atoms on treatment with either bis(trimethylsily1)peroxide or sulfur. However, with selenium, only a triselenide could be obtained.'97 The tricyclic species (134) has been obtained from the reaction of o-bis(phosphin0)benzenewith sulfur.19* Nucleophilic attack at a sulfur atom of N-aryliminodithiazoles leads to ring-opening, and, after protonation, N-arylcyanothioformamides are isolated, together with triphenylphosphine-oxide and -sulfide.199

Strong interest continues in the Mitsunobu reaction and its applications in synthesis. The effect of the strength of the carboxylic acid component of Mitsunobu esterifications has been studied. The reactions of carboxylic acids with the triphenylphosphine - diisopropyl azodicarboxylate system in the absence of an alcohol give a mixture of mono- and bis-acylated hydrazides and the carboxylic acid anhydride, arising from attack of the carboxylate anion on the triphenylphosphonio group of the initial adduct, weaker acids reacting faster than stronger acids.200 Mitsunobu reactions are included in a review of the synthesis of phosphorus compounds by solid phase techniques.201Solid phase procedures have been described for the esterification of polymer-supported hydroxyl groups,2o2and the conversion of supported phenols to related phenolic ether^,^^^^^^ using the Mitsunobu approach. The Mitsunobu reaction has now been used for the synthesis of phosphorus acid esters. Thus, e.g., combination of triphenylphosphine, diisopropyl azodicarboxylate, and a dialkylphosphite, followed by addition of an alcohol, results in the formation of unsymmetrical trialkyl p h o ~ p h i t e s .Phosphonic ~~~ acid salts have also been converted into related phosphonate esters using a modified Mitsunobu approach.206A general procedure for Mitsunobu inversion of sterically hindered alcohols has been developed.207Efficient Mitsunobu transformations of the hydroxyl group of Nprotected serine esters have been described.208The triphenylphosphine-diethyl

I : Phosphines and Phosphoniwn Salts

19

azodicarboxylate system has been applied to the synthesis of monoprotected 2alkylidene-1,3-propandiol~,~~~ perfiuoro-t-butyl ethers,210and to the conversion of hydroxyesters into the corresponding nitrile esters, thereby enabling a procedure for carbon elongation.21' v 2 l 2 Trialkylphosphoniocyanomethyleneylides have been shown to mediate Mitsunobu promoted alkylations with active methine compound^,^^ and also the dehydrocyclization of diols and aminoalcohols to form six-membered oxygen- and nitrogen-heterocyclic systems.214 N-Benzyltriflamidehas found use as a nucleophile in the synthesis of primary and secondary benzylamines from the corresponding alcohol by the Mitsunobu have been obtained in good yield reaction.215Dialkyl-2-aminoalkylphosphonates in a one-pot procedure employing the Mitsunobu reaction of dialkyl 2-hydroxyalkylphosphonates with hydrazoic acid, and subsequent treatment of the intermediate azides with triphenylphosphine, followed by hydrolysis of the resulting iminophosphoranes with water.216Mitsunobu procedures have also been developed for the direct preparation of protected hydrazines from alcohols,217the alkylation of p-toluenesulfonamides (enabling a new route to primary and secondary amines),218the alkylation of tetrazo1es2l9and heterocyclic amidines (giving a route to L-amino acid derivatives),220and for the synthesis of Ntriphenylphosphoranylidene nucleosides.221 Nucleophilic attack at nitrogen has also been identified in a study of the reactions of triarylphosphines with tetracyanoethylene in aqueous acetonitrile. In contrast, the related reactions with tetracyanoquinodimethane (TCNQ) involve one electron transfer from phosphorus to the TCNQ molecule.222Full details of the reactions of tertiary and ditertiary phosphines with bromophenyldiazirines have now appeared.223Interest in the Staudinger reaction of tertiary phosphines with azides has also been maintained. A spectroscopic study has shown that the sequence of addition of reactants alters the course of the Staudinger reaction of azides in the presence of acyl derivatives.224The Staudinger reaction of a-azidophenylacetonitrile with triphenylphosphine unexpectedly results in the formation of the salt (1 35).225 Applications of the Staudinger reaction in synthesis

have been d e s ~ r i b e d .Phosphazenes ~ ~ ~ . ~ ~ ~ have also been characterised from the reactions of triphenylphosphine with heteroaromatic azides,228 fluorinated 2-diazo-1 , 3 - d i k e t o n e ~and , ~ ~cyclic ~ sulfur-nitrogen compounds.230The adduct of triphenylphosphine with aluminium trichloride has been studied by solid state 31P NMR, using the INEPT technique.231

1.2.4 Miscellaneous Reactions of Phosphines. - The new water soluble phosphine (136) has been prepared via lithiation and phosphonation of p-bromophenyldiphenylpho~phine.~~~ The reactivity of the phosphine (137) towards alkyl halides has been compared with that of the related arsine and stibine. Surprisingly, the latter react faster than the phosphine. Also reported is the

20

Organophosphorus Chemistry

Ph2PG!(OPh)2

@-: -

Br&l---=O -

OMe (136)

(137)

OMe (138)

formation of the phosphine oxide (138) on treating (137) with N-bromo~ u c c i n i r n i d e . ~The ~ ~ reactivity of the amino group of 2-aminophenyldiphenylphosphine has been utilised for attachment of the phosphine to a chiral platform, giving the new chiral diphosphine (139).234 The functionalised phosphine (140) has been used as a spacer group in the synthesis of surface phosphino-functionalisedd e n d r i m e r ~On . ~ ~the ~ basis of spectroscopic studies of the products derived from (141) on sulfuration at phosphorus and reduction of the carbonyl group, it has been concluded that a trans-ring function is present in (141).236A variety of stannylphosphines has been obtained in a study of the 0

95

MeN

Ph

reactivity of silylphosphines with dichlor~dimethylstannane.~~~ It has been established that the carbon-phosphorus bond in phosphino-dicarbaclosoborane systems is very susceptible to cleavage.238Photolysis of the diboretane (142) provides a route to the bicyclic system (143).239 The reactivity of secondary phosphines has received some attention. Treatment of dicyclohexyl- and diisopropyl-phosphine with phenacyl bromide, followed by a base, yields the phosphines (144), which, on subsequent treatment with sodium bis(trimethylsilyl)amide, are converted to the enolate salts (145), of interest as ligands tYP

tYP

08,

0B\ P? \P

I tmP

I tmP

WB/PA (142) R = Bu'

(143)

R2PCH2COPh

HXph 0-Na+

R2P

(144) R = Cy or Pr' (145)

in coordination chemistry.240Secondary phosphines bearing bulky groups such as 1-adamantyl or triphenylmethyl have been shown to react with trifluoracetic anhydride to give the trifluoroacyl phosphines (146).241 The phosphinodioxaborinane (147) has been prepared from diphenylph~sphine."~Metalmediated reactions of phosphines have also received some attention. Rh(1) -

1: Phosphines and Phosphonium Salts

21

0

"B -Ph

II

d

R' R2PCCF3 Ph2P (146)

R'

= R2 = 1-Adamantyl R' = Ph, R2 = Ph3C

( 147)

IA;

OPPh2 CCH2CH2R 11

0 R = H, Pr, Bu, Ph or C6F5

PPh2 PPh2 (149)

catalysed hydroacylation of alkenes and alkynes, using o-diphenyl-phosphinobenzaldehyde as the acylating agent, has enabled the preparation of the ketophosphines (148).243Novel intramolecular Michael-type reactions between vinyldiphenylphosphine and pentamethylcyclopentadienylrhodium(I1I) complexes have given the related complexes of heptadentate 10e ligands, e.g., (149).244 Treatment of the optically active dihydrophosphole (150) with a dicyclopentadienylzirconium chlorohydride complex, followed by chlorodiphenylphosphine, gives the chiral diphosphine (151), isolated as the related dis~lfideA . ~ ~zirconium ~ hydride complex has been shown to promote the cyclooligomerisation of primary phosphines, forming cyclopolyphosphines (RP)s."~ Tungsten pentacarbonyl has been used as a protecting group for the phosphorus centre of phosphines bearing basic groups, e.g. dimethylamino, in their reactions with alkylating agents.247A new palladium(I1) complex of a chiral amine has been applied to the resolution of t-butyl(methy1)phenylp h o ~ p h i n e Further .~~~~ instances ~ ~ ~ of phosphorus - carbon cleavage processes have been recognised in the chemistry of metal-phosphine complexes used in homogeneous c a t a l y ~ i s . ~ ~ ~ * ~ ~ An analysis of the effects of substituents on the basicity of phosphines has been presented,255and the relationship between phosphine-proton affinities and lone pair density properties explored.256A scale of o-donor strengths for phosphines and related systems has been developed. The model supports the view that as 0donor strength increases, so the It-acceptor power declines.257 Theoretical approaches to the electronic structures of p h ~ s p h i r a n eand ~ ~ ~1,3-diphosphe-

22

Organophosphorus Chemistry

tane259have been described. The molecular structure of chloromethylphosphine has been determined by gas-phase electron diffraction, and correlated with the results of ab-initio calculations.2M)The molecular structure of the diphosphaanthracene (152) has been determined. The redox potential of this system indicates that it has some potential as an electron-donor, and black, semiconducting adducts with TCNQ, and iodine, respectively, have been isolated.261 Structural studies of 8-dimethylamino-1-naphthylphosphines, e.g., (1531, have revealed the existence of nitrogen-*phosphorus coordinative interactions. Similar interactions are present in the related phosphine oxides and phosphonium A structural study of the o-hydroxymethylphenylphosphine(154) sa1ts.262*263 shows that the three hydroxymethyl substituents are in close proximity to the Et

-

Me2N: I

PPh2 1

CH20H

lone pair at phosphorus.264X-ray techniques have also been used to determine the absolute stereochemistry of the chiral phosphine (15 9 , present in a palladium complex.265The absolute configuration of the related diphosphine (156) has been determined by NMR techniques, and the mechanism of its previously reported

stereoselective synthesis explored.266The influence of substituents in the ferrocene system of 1,l-bis(diphenylphosphino)ferrocinium cations has been investigated by electrochemical techniques.267A bis(pentafluoropheny1)phosphinate anion (m/z 397) has been observed in the negative ion FABMS spectrum of tris(pentafluor0phenyl)phosphine.268The generation of trivalent phosphorus cation radicals, R3Po+, by the reaction of phosphines with electrophiles via a single electron transfer pathway, has been reviewed. Such radicals can either undergo electrophilic reaction with a nucleophile to give the corresponding phosphoranyl radical, F~PNU]',or couple with another radical. Which route is followed is controlled by the substituent groups at phosphorus, and the extent to which the unpaired spin is d e l o ~ a l i s e dIn . ~a~further ~ development of this area, it has been shown that tributyl- and diethylphenyl-phosphines are converted to the corresponding cation radical in the presence of methylviologen via a single electron transfer process. These then react with alcohols or thiols by an ionic mechanism, which ultimately leads to the related phosphine oxide or sulfide.270 A radical abstraction pathway has been observed in the reactions of radical cations derived

I : Phosphines and Phosphoniwn Salts

23

from methylphosphine, trimethylphosphine, and trimethyl phosphite, with dimethyldisulfide and dimethyldi~elenide.~~~ The chemistry of phosphinocarbenes has continued to

2

Halogenophosphines

2.1 Preparation.- Fluorophosphines have been obtained from the reactions of the related chlorophosphines with trimethyltin Phenyl(isopropy1)fluorophosphine has been resolved via a chiral amine-palladium(I1) complex, providing the first example of the resolution of a free fluorophosphine chiral at phosphorus. This compound racemises at 20 "Cin benzene solution over six hours. The neat compound rapidly decomposes by redox di~proportionation.~~~ The same approach has been used for the resolution of the related chloro-phosphine, but the optically active compound could not be liberated unchanged from the crystallised diastereoisomeric palladium complex.276The dihalo-genophosphines (157) have been prepared from the reaction of a sodio-cyclopentadienidereagent with the appropriate phosphorus trihalide. X-ray studies confirm the structure in the solid state, but these compounds are fluxional in solution.277Routes to bis(1adamanty1)chlorophosphine have been developed. Despite the steric crowding, this compound reacts readily with water to form the related secondary phosphine Oxidative decomplexation in hexachloroethane of the 1,3-diphosphete (158) coordinated to various metals provides a novel route to the P2C2 heterocyclic halogenophosphines (159) and (160).279A new, efficient, route to a series of borane-protected, and free, chlorodiorganophosphinesbearing a wide range of functionalised and chiral substituents, e.g., (161), (162), is provided by the reactions of organozinc reagents with diethylaminodichlorophosphine,

(157) X = CI or Br

(158)

followed by treatment with hydrogen chloride and protection with borane.280A Grignard procedure has been used in the synthesis of the hindered dichlorophosphine (163), which can be reduced to the related primary phosphine with lithium aluminium hydride.281Direct phosphonation of heterocyclic systems with phosphorus trihalides in the presence of a base has been applied to the (165),283and synthesis of a range of new dihalogeno-phosphines, e.g., ( (1 66).2&4 Regiospecific photochemical addition of phosphorus tribromide to

24

Organophosphorus Chemistry

M e Me $- ( -

Q

aNyMe Br,

,PBr2

,c=c,

PBr2

H

SiMe3

alkynes and alkenes has been explored as a route to novel functionalised halogenophosphines, e.g., (167).285p286

Reactions. - The reactions of diorganoiodophosphines with varying quantities of iodine have been studied by NMR techniques, which indicate the formation of a dialkyldi-iodophosphoniumiodide as the initial product, followed by polyhalide anion formation in the presence of excess iodine.287A modified McCormack synthesis of 3-silylated phosphol-3-enes (168) from phenyldichlorophosphine and 2-silylated 1,3-butadienes has been described. The reaction is carried out in the presence of a small amount of copper stearate in acetic anhydride at 50 "C, these conditions preventing the complete desilylation observed under standard conditions.288The consecutive reaction of lithium phenylacetylide with triphenylborane and diphenylchlorophosphine results in the formation of the intramolecularly coordinated phosphino-borane (169).289 Treatment of the alkoxyvinyldichlorophosphines (170) with Grignard reagents 2.2

SiR3

0"

p h \ F ? ?

Ph Ph2P+B?h2 (169)

X2PCR'= C(R2)(OR3) (170) X = CI or Br R' = H,alkyl, or Br R2 = H, alkyl, CI, Br or OR R3 = alkyl

has given a series of functionalised p h o s p h i n e ~ .The ~ ~ ~ reaction of the aryldichlorophosphine (171) with chloroform in the presence of lithium diisopropylamide gives the phosphine (172), which, on subsequent treatment with butyllithium, is converted into the phospha-alkene (173).291The bis(ylidy1)phosphines (174) have been prepared from the reactions of phosphonium ylides with dihalogenophosphines. These compounds can be protonated at the ylidic carbons but alkylated and oxidised at the central phosphorus.292Full details have appeared of the reactions of halogenodiorganophosphines with bicyclic bases

1: Phosphines and Phosphonium Salts

Me

25

Me

Me

such as DBU and DBN, which give products which are formally complexes of phosphenium cations, arising by nucleophilic displacement of halogen from phosphorus.293 On treatment with DBU, bis(trimethylsily1)-methyl-dichlorophosphine is converted to a complex polycyclic structure having a diphosphete central unit.294The reactions of chlorophosphines with N,N-dimethylamino-ptoluenesulfenamide have been explored, and a series of ionic products isolated.295 As usual, a number of reports have appeared of the reactions of Ph

Ph (174) R = H, Me, Bu or Aryl

(175)

halogenophosphines with oxygen nucleophiles. The reaction of racemic chiral diorganochlorophosphines with a chiral sugar reagent has given chiral alkoxyphosphines which have been isolated in an enantiopure state, and then used to prepare chiral phosphines by further nucleophilic displacement reactions at phosphorus.296The functionalised phosphonite esters (17 9 , prepared from the reaction of the related monoorganodichlorophosphine with a phenolic aldehyde in the presence of base, have been used in the synthesis of phosphorus-containing macro cycle^.^^^ Related chemistry has been reported in the reactions of 1-adamantyldibromophosphine with a functionalised phenol reagent, again leading to macrocyclic systems.298Phosphinite esters prepared from chlorodiphenylphosphine and enediynols have been shown to undergo low temperature tandem allene radical cyclisations to form 2,3-dih~droindenes.~~~ Nucleophilic displacement reactions on 1,2-bis(dichlorophosphino)ethane coordinated to a metal ion have also been reported.300A detailed vibrational spectroscopic study of n-propyldichlorophosphinehas been reported,301and the molecular structure of a series of vinyldichlorophosphines probed by electron diffraction techniques.302

3

Phosphine Oxides

Preparation. - The reaction of diphenylphosphinyl chloride with dicyclopentadienylsamarium (or samarium diiodide), followed by an alkyl halide (or alkyl tosylate, epoxide, or a$-unsaturated ketone), provides a route to a 3.1

26

Organophosphorus Chemistry

variety of functionalised phosphine oxides, e.g. (176).303A route to the 1(benzotriazol-1-yl)alkyldiphenylphosphine oxide (177, R=H) is provided by the reaction of N-(chloromethy1)benzotriazole with the diphenylphosphinous anion. Subsequent lithiation a to phosphorus, followed by alkylation, provides the related systems (177, R=alkyl) which have found use in the synthesis of benzotriazol-l-yl substituted cyclopropane~.~" A synthetic route to the phosphine oxide (178), of interest in connection with its non-linear optical 0 II

P h 2 ! 0

Ph2PCH2CH(OH)Me

CH= CHM *.e2

A P IIh 2

(176)

0

(178)

(177)

properties, has been developed.305 A conventional Arbuzov reaction of methyl diphenylphosphinite with 2,6-bis(chloromethyl)pyridine provides the diphosphine dioxide (179), the coordination chemistry of which has been explored.306The stereochemistry of the major endo adduct (180) obtained from the Diels-Alder addition of (S)-methylphenylvinylphosphine oxide and cyclopentadiene has been determined by X-ray techniques.307 Cycloaddition reactions of dihydrophosphinineoxides and dimethylacetylenedicarboxylatehave

given the bicyclic system (18 l).308 Routes to chiral dibenzo[bflphosphepines, e.g., (182),309and the carbohydrate-based heterocyclic system (183)310have been developed. An improved route to the diphosphine dioxide (184) is provided by the reaction of the related bis(aromatic aldehyde) with diphenylphosphine in concentrated hydrochloric acid, followed by treatment with aqueous formic acid.31* A series of a-hydroxyalkylphosphine oxides and sulfides has been obtained from the reactions of dimethylphosphine oxide or sulfide with aldehydes and ketones.312 The unsymmetrical diphosphine dioxides (185) have been prepared by the base-promoted addition of secondary phosphine oxides to vinyldiphenylphosphine oxide.313Routes to cyclopendant diphosphine dioxides, e.g., (186), have been developed, and their acid-base properties The 1,3-dien-2-ylphosphine oxides (187) have been obtained from the reactions of aallenols with chlorodiphenylphosphine in the presence of triethyla~nine.~'~ Routes to 1,3-dienyl-(and 1-en-3-ynyl)-phosphine oxides have also been developed from C-C coupling reactions of alkynylphosphine oxides;316 1,3dienylphosphine oxides are also accessible via isomerisation of the alkynyl-

1: Phosphines and Phosphonium Salts

27 0

R2

OAc (181) R' = Ph, Me or OR R2 = H or Me

Ph;P=O (185) R = alkyl (187) R' = Me,Bu or PhCEC R2 = H or Me

(186)

phosphine oxides (188) in the presence of trib~tylphosphine.~'~ The reaction of the carbanion derived from chloromethyldiphenylphosphine oxide with nitrobenzenes, e.g., p-bromonitrobenzene, proceeds in an unexpected manner, with predominant replacement of the hydrogen ortho to the nitro group, to give nitrobenzylphosphine oxides, e.g., (1 89).318Several groups have described routes to calixarenes bearing diphenylphosphinylmethylsubstituents at a rim,319*320 e-g. (1 Phosphine oxides bound to polystyrene and polyacrylate polymers have 9

0 II

Ph2P-CECCH2CH2R

@

P! h2 NH

(188) R = Me, Et, Pr or Bu

Br

4

0Ph2P

II 0

(190) n = 4 o r 5

also been prepared.322A series of y-trimethylstannylpropylphosphinechalcogenides (191) has been prepared, and the possibility of intramolecular coordination to tin explored.323'The heterocyclic system (192) has been obtained from the reaction of ethynylaminophosphines with thio- or dithiocarbonic a ~ i d s .Selective ~ ~ ~ phosphonium * ~ ~ ~ salt formation and alkaline hydrolysis are the

28

Organophosphorus Chemistry

Me2SnCH2CH2CH2PPh2

Z

P

F

R

R,pyv;/vp:R 0

O .\

I

Y (191) X = O , S o r S e Y = F, CI, Br or I

8f\

S Ph (192) R = Ph, Bu or Me3Si

(193) R = dodecyl

key steps in the synthesis of a range of diphosphine dioxides, e.g., (193), of interest as selective extractants for actinide elements.326

3.2 Reactions. - Further examples have appeared from Warren’s group of the elaboration of alkyldiphenylphosphine oxides to give reagents for Horner-Wittig procedures; these will be detailed elsewhere in this v o 1 ~ u n eThe . ~ use ~ ~of~ such ~~~ functionalised alkyldiphenylphosphine oxides as Horner-Wittig reagents has also been reviewed.330Warren’s group has also established that a-lithiated alkyl diphenylphosphine oxides are not configurationally stable, even in their reactions with electrophiles at - 78 0C.331 Mixtures of functionalised phosphine oxides, (194) and (195), are obtained from the reactions of a-lithiated ally1 diphenylphosphine with ep~xides.”~Side-chain elaboration of P-hydrazonophosphine oxides and sulfides has provided a route to phosphine oxides and 9332

(194)

(195)

(196) X = O o r S

sulfides bearing pyrazolyl substituents, e.g., (196).3349335The P-oximinophosphine oxides (197) have been obtained from the nucleophilic addition of hydroxylamine A small degree of asymmetric induction is ethers to allenylphosphine observed in the metallation of ferrocenyldiphenylphosphine oxide with an Nlithiated chiral base, followed by treatment with trimethylsilylchloride,to give the system (198), which can be reduced to the related phosphine on treatment with lithium aluminium h ~ d r i d e Treatment .~~~ of a-cyanomethyldiphenylphosphine oxides with powdered alkali metal hydroxide in acetonitrile, followed by addition

0 II NC (199)

R1 = Et or Ph R2 = Jkyl or awl

I : Phosphines and Phosphonium Salts

29

of an acid chloride, provides a route to the enolic systems (199).338 The Williamson reaction of chloromethyldimethylphosphine oxide with sodium alcoholates of aminoalcohols has given a series of (aminoalkyloxymethy1)dimethylphosphine oxides.339Phosphine oxides may be converted into the related phosphinimines, R3P=NH, by repeated sequential treatment with triflic anhydride, generating the salt (200), followed by treatment with ammonia.340The addition of simple lithium-, sodium-, and magnesium salts has been shown to influence the course of alkylation of ethoxycarbonyl-methylphosphine oxides in the presence of a base.341The regiochemistry of addition of a-methoxyallylphosphine oxides to a,P-unsaturated carbonyl compounds has been Cyclopropylphosphine oxides have been shown to react with the sodium salts of various amides to give dihydropyrrole derivatives via initial ringopening and a subsequent intramolecular Wittig-Homer reaction.343 Further studies of hydrogen bonded adducts of phosphine oxides have been reported. An FT-IR study of the phosphine oxide-methanesulfonic acid system is consistent with dipole-dipole interactions, which are confirmed by o ~ m o m e t r y . ~ ~ Surprisingly, the hydrogen bond interaction between an iridium hydride system and triphenylphosphine oxide seems to be stronger than that between the phosphine oxide and some N-H bonds, but weaker than between the phosphine On flash vacuum pyrolysis, the fused system (201) is oxide and a converted with deoxygenation into the benzophosphepin (202).346Separation of

enantiomers of chiral phosphine oxides has been achieved by HPLC.347Addition of the non-ionic surfactant, dodecyldimethylphosphine oxide has been shown to inhibit SN2 reactions catalysed by cetyltrimethylammonium bromide.348 Diphenylphosphine oxide has been shown to interact reversibly with 10methylacridinium salts to give the N-quaternary salts (203).349 Tris(2pyridy1ethyl)phosphineoxides undergo conventional quaternization on treatment with alkyl halides to form the related salts (204).350The aminomethylphosphine oxide and sulfide (205; R=H) are converted into the related trimethylsilyl derivatives (205; R=Me3Si) on treatment with diethyltrimethylsilylamine. Subsequent treatment with diorganochlorophosphines provides the phosphinoPh2P=O

I

X II MeP-CH2-N-Me I

R

3x-

(205)X = 0 orS

30

Organophosphorus Chemistry

aminoalkylphosphine chalcogenides (205; R=R2P).351The diphenylphosphinoyl and diphenylthiophosphinoyl groups have been shown to be, respectively, modest and strong P-effect functionalities in promoting the solvolysis of mesylates of type (206).352It has been shown that the iodoalkylphosphine sulfides (207) undergo a solvent dependent intramolecular cyclisation to form the salts (208).353 The reactivity of the phosphine selenides (209) towards alkyl halides has also been studied.354

(206) X

=

0 or S

(207)

I-

n = 3 or 4

'OMe

(208) n = 3 o r 4

'

3-n

(209) n = 0-3

3.3 Structural and Physical Aspects. - The X-ray crystal structure of tris(2,6dimethoxypheny1)phosphine selenide (209; n=O) shows that the phosphorusselenium bond distance is the longest among those of the reported triarylphosphine selenides, and provides evidence of a coordinative interaction between the methoxy oxygen atoms and p h o s p h o r ~ s .The ~ ~ crystal and molecular structures of a series of diastereomeric 2-phosphinoyl-, 2thiophosphinoyl-, and 2-selenophosphinoyl-substituteddithianes (210),355and of the 4-t-butylphosphorinane-1 -sulfide derivatives (211),356 have also been reported. The conformational properties of the bicyclic phosphabicyclodecanones (212) have been investigated by NMR techniques. These compounds, which exist in the thermodynamically most favourable chair

(210) X = 0, S or Se

Ph (211)

(212) 2 - O o r S

conformation with a trans junction of the rings, have a high conformational stability due to the nature of ring substitution and a specific effect from the second heter~atom.~~' X-ray structures of the ferrocene systems (213),358and of a diastereoisomeric menthyl ester of the chiral phosphino acid (214),359have also been described. A detailed mass spectrometric study of a series of tetraalkyldiphosphine disulfides has been r e p ~ r t e dThe . ~ ~structure of the tripletstate phosphoryl biradical(215) has been confirmed by an ESR

3.4 Phosphine Chalcogenides as Ligands. - The enhanced stability provided by two triphenylphosphine oxide ligands has enabled the first crystal structure analysis of a non-haem-di-iron-dioxygen adduct,362 Complexes of the bis(phosphine oxide) (213; Z=O) with copper(1) and ~ o p p e r ( I I ) and , ~ ~ ~of the related disulfide (213; Z=S) with gold(1) and ~ i l v e r ( I )have , ~ ~ been characterised.

I : Phosphines and Phosphonium Salts

31

Z

Z (213) Z = 0 or S

Complexes of triphenylphosphine oxide with r h e n i ~ m ( V and ) ~ ~indium(II1) ~ have also been described. The synthesis and structural characterisation of the lithium salt and the zinc complex of the hydroxyalkenylphosphine oxide (216) have been reported.367Further examples of the coordination of triphenylphosphine oxide to organotin acceptors have appeared,368 and a reagent system consisting of tributyltin hydride, tributyltin iodide, and a phosphine oxide has been used to reduce functionalised epoxides to the corresponding alcohols with high chemoand regio-~electivities.~~~ Trioctylphosphine oxide, and bis(dipheny1phosphinoy1)methane have been used as components of synergistic extraction systems for alkaline earth and alkali metals.370The coordination chemistry of bis(dipheny1phosphino)methane-mono- and di-sulfides and selenides has attracted considerable a t t e n t i ~ n ,as ~ also ~ ~ .has ~ ~that ~ of the oxides, sulfides, and selenides of the related bis(phosphin0)amine (21 Complexes of triarylphosphine oxides with selenium dioxide have been c h a r a ~ t e r i s e d . ~ ~ ~ 7).3759379

Triphenylphosphine-oxide, -sulfide, and 1,2-bi~(diphenylphosphinoyl)ethane have found use as reagents for the selective liquid-liquid extraction of silver@) and mercury(I1) from their binary mixtures with other di- and trivalent metal ions.38'

4

Phosphonium Salts

4.1 Preparation. - A range of 1,3-dithianylphosphoniumsalts (218) has been prepared in the course of further studies of sulfur lone pair anomeric effects in these s y ~ t e m s .Conventional ~ ~ ~ * ~ ~ quaternization reactions have been used in the synthesis of the salt (219)385and a range of polymer-supported phosphonium salts (220).386 A new efficient route to salts of the type (221) has been developed.387The a-azolylalkylphosphoniumsalts (222) are readily accessible from the reactions of the corresponding o-bromoalkylphosphonium salts and a ~ o l e s . Routes ~ * ~ to vinylphosphonium salts, e.g., (223), continue to be explored, and their reactivity utilised in the synthesis of phosphonium salts bearing heterocyclic substituents, e.g., (224).389*39'The betaine (225) has been

32

Organophosphorus Chemistry 0

(219)

(221) X = e.g., C02Me

(220) n = 3,4, 6 or 10

(222) n = 2 o r 3 X = CH or N

obtained from the reaction of a methylenetriphenylphosphorane with hexamethylcyclotrisilathiane. Alkylation at sulfur provides the related phosphonium salt.392The arylazophosphoniumsalt (226) has been isolated from the reaction of a cyclopalladated diarylazo ligand with triphenylphosphine in the presence of

acid.393Improved routes to the triazaphosphonioadamantane system (227) have been described. On subsequent treatment with sodium in liquid ammonia, these salts undergo phosphorus-carbon cleavage reactions to give the parent triazaphosphaadamantane and the bicyclic system (228).394 The formation of hydroxymethylphosphonium salts, from the appropriate primary, secondary, or tertiary phosphine, formaldehyde, and hydrochloric acid, provides an excellent means of characterising phosphines by electrospray mass spectrometry.395The formation of alkoxytriphenylphosphonium salts by anodic oxidation of triphenylphosphine in the presence of an alcohol and perchloric acid has been reinvestigated, and a range of new systems described.396The stabilisation of unusual anions in the presence of phosphonium cations continues to be a successful strategy, and many new salts have been described, involving p~lyhalide,~~’@~ and complex silicon,403tin,404arsenic,a5 b i s m ~ t h , and ~~.~~

1: Phosphines and Phosphonium Salts

33

R

(227)R = Me, Et, Ph, PhCH2 or Cy

boronm7 anions. Perhaps of special interest for this volume is the salt (229), involving an undecaphosphide anion.408 4.2 Reactions. - The equilibrium acidities (pKHA) of six p-substituted benzyltriphenylphosphonium salts, and also those of related allylphosphonium salts, have been determined, together with the homolytic bond dissociation enthalpies of the acidic C-H bonds.409 A study of the data available in the Cambridge Structural Database reveals that tetraphenylphosphonium cations in crystals associate through phenyl-phenyl non-bonded interactions which are attractive, concerted, and widespread in nature. An attractive force of 60-85 kJmol- has been calculated.410 Phosphonium salts have been shown to be effective hosts for phenols, and to some extent, alcohols. Isomers and enantiomers of these guests can be easily separated by such complexation. The approach has also been used to resolve chiral phosphonium salts by the use of a resolved phenol, e.g., a binaphth01.~~~ The reactions with aqueous alkali of a series of 240- and p-triphenylphosphoniopheny1)-benzimidazoles and -benzothiazoles (230) have been investigated. Evidence of a neighbouring-group hypervalent interaction between the pyridine-like nitrogen of the benzazole and the 2-(o-triphenylphosphoniophenyl) substituent has been presented from the results of a study of the course of alkaline hydrolysis of the salts and a comparison with that of the related 2-@-triphenylphosphoniophenyl) systems in which such hypervalent interactions are not possible. Hydrolysis of the latter proceeds abnormally, in some cases, with the formation of biaryl coupling products in addition to the expected hydrolysis products. Curiously, both series of salts undergo hydrolysis according to a second order rate law, rather than the usual third order process. Treatment of the salts derived from benzimidazole (230; X=NH) with one equivalent of alkali gives the stable phosphonium betaines (23 1). The ortho-isomer exhibits a marked shielding of the 31Pnucleus compared with the para-isomer, consistent with a hypervalent interaction between nitrogen and phosphorus.412The alkaline hydrolysis of pand y-heterosubstitutedalkylphosphonium salts, e.g., (232), has been used as the

aGq / \

K

&

R

2

\ /

= S,NH or ?Me R1 = H or Ph3P B r R2 = Ph3@B r or H

(230)X

+

(2311

PPh3

Ph$CH*CH20H

Bf

(232)

34

Organophosphorus Chemistry

basis of a synthetic method to obtain diphosphine dioxides. Whereas hydrolysis of the P-functional salts often proceeds in an anomalous manner, that of the related y-functional salts occurs in a predictable fashion, usually with cleavage of one phenyl group.413Cleavage of phosphorus-carbon bonds has been observed in the reactions of phosphonium salts with palladium ~omplexes.4~~ The salt (233) unexpectedly undergoes solvolysisin aqueous methanol to give triphenylphosphine and the related 3-hydroxytriazine system.41s Thermolysis of 2-(N-acylamino)benzyl methylethers, in the presence of an acid catalyst, and triphenylphosphine, or alternatively of the salts (234), serves as a novel method for the synthesis of the indole ring system. A phosphonium salt intermediate is almost certainly involved in the reaction of the benzyl methyl ethers, these reactions appearing to be essentially intramolecular Wittig reactions in which the halide or other counterion acts as a base under the high temperature conditions prevailing.416The radicalpromoted cyclopolymerisation of diallyldiphenylphosphonium bromide to give polymers containing the units (235) and (236) has been reinvestigated, and the

alkaline hydrolysis and Wittig reactions of the cycloalkylphosphonium moieties studied. Alkaline hydrolysis, as expected, proceeds with loss of a phenyl group, whereas Wittig reactions occur with ring cleavage to give polymeric phosphine oxides, e.g., (237).417Good yields of the cyclopropylphosphonium salts (238) have been obtained from the reactions of vinylphosphoniurn salts with sulfoxonium ylides in the presence of DBU in dichloromethane. In the presence of inorganic base systems, these salts usually undergo hydrolysis with the expected loss of a phenyl A new insertion reaction of phenylisocyanate into a C-C bond of the phosphonium zwitterions (239), to give the adducts (240), has been reported."19 The betaine (241) has been isolated from the reaction of (2benzimidazolylmethy1)triphenylphosphonium chloride with benzoyl isothiocyanate in the presence of triethylamine."20 The reaction of cyanomethyltriphenylphosphonium chloride with triethoxymethane in acetic anhydride gives the bisphosphonium ylide system (242) which on subsequent treatment with acid yields the heteroarylphosphoniumsalt (243)."21 Treatment of the diphospha-ally1

1: Phosphines and Phosphonium Salts

35

(239) R’ = Pr, Bu or Et2N R2 = Me or Et

salt system (244) with sodium bis(trimethylsi1ylamide) results in the formation of the cyclic phosphorane-ylide (245).422Condensation of the diphosphoniopropenide salt (246) with a halogenophosphine, in the presence of a base, yields the cyclic system (247), which, in the presence of further halogenophosphine and a reducing agent, undergoes ring expansion to give, e.g., (248). When the exocyclic substituent at the phosphorus atoms is halogen, these compounds can be reduced to the delocalised system (249).423

Methyltriphenylphosphonium borohydride has been found to be a useful reagent for the selective reduction of aldehydes and ketones to alcohols, and acid chlorides to alcohol^.^" Tetraphenylphosphonium hydrogen difluoride has proven to be an effective and convenient catalyst for silyl-mediated aldol reactions and the addition of silylacetylenes to carbonyl c o m p o ~ n d s . 4The ~~ activity of poly(oxymethy1enes) terminated at both ends by phosphonium groupings, as phase-transfer catalysts, has been compared with the activity of non-ionic analogues.426The reactivity of phenyl radicals bearing a phosphonium substituent, e.g. (250), as hydrogen abstracting agents has been studied by mass

Ph

Ph

Ph

(246)

(247) R = Ph or halogen

(248)

R

@+Me3

Ph (249)

R

R

(250) R = H orF

36

Organophosphorus Chemistry

spectrometric techniques.427The electron impact and fast atom bombardment mass spectra of alkyltriphenylphosphonium (and related arsonium salts) have been compared.428Structural studies on a series of quasi-phosphonium salts containing P-0, P-N, and P-S bonds have also been reported.429 5

px - Bonded Phosphorus Compounds

A review of the thermal reactions of various classes of organophosphorus compounds contains much that is relevant to this section.430The unsymmetrical, stable diphosphenes (251), carrying bulky aryl and aryloxide substituents, have been prepared by the reaction of lithium 2,4,6-tri-t-butylphenylphosphidewith the corresponding arylphosphorodichloridites, followed by DBU-induced dehydrochlorination. With sulfur or selenium, the corresponding thiadiphosphiranes or selenadiphosphiranes, respectively, are formed. Dichlorodiphosphiranes have * been isolated from the reactions of these diphosphenes with dichl~rocarbene.~~ The coordination chemistry of the diphosphenes (251) has also been Dihalodiphosphiranes have also been isolated from the corresponding reactions R’

Ar-P=P-0

)=\ Ar-P=P-R

Ar-PAP-R

R3 (251) Ar = 2,4,6-But3C6H2 R1 = But or Bus R2 = H, Me or But

(252) Ar = 2,4,6-BUt&H2 R = (Me~si)~C

(253) X = halogen

of dihalocarbenes With the diphosphene (252). Structural studies of these adducts have revealed the shortest P-P bonds ever observed in the diphosphirane series. Such dihalodiphosphiranes have also been shown to undergo anionic ringopening to form the stable 1,3-diphospha-a1lylanions (253).433The new diphos@-P=P-Ar

I

Fc,

,Ar P-P

Fe

I

P-P FC’ (254) Ar = 2,4,6-BUt3C6H2

(255)

I

‘Ar

Fc = ferrocenyl

[nr -P=P- PR ‘2R2

1

+

(256) Ar = 2,4,6-But&H2 R2N = Pri2N,tmp or Cy2N

OTf -

(257) R1 = But or H R2 = But or 2,4,6-But&H2

I : Phosphines and Phosphonium Salts

37

phene (254) has been prepared. It represents a borderline case for dimerisation, forming the tetraphosphorus system (255) which undergoes cycloreversion to the diphosphene on heating in ~ y l e n eTreatment .~~ of the diphosphenes (256) with a tertiary phosphine in the presence of trifluoroacetic acid leads to the formation of the stable salts (257), which are the first phosphine donor-stabilised adducts of the phosphanetriyl cation [Ar P = Complexation of the cations of dipotassium di-t-butyldiphosphide with a cryptand in THF gives solutions which contain the protonated monoanion (258) and the diphosphene radical anion (259). The corresponding triphosphene radical anion (260) has also been ~ h a r a c t e r i s e d .Mixtures ~~~ of symmetrically substituted diphosphenes have been shown to undergo metathesis (analogous to olefin metathesis) in the presence of a tungsten[O]phosphine complex and a dihalogenophosphine, to form unsymmetrically disubstituted systems, e.g., (261). In this work, it was also noted that treatment of a dihalogenophosphinewith the above tungsten complex also leads to a symmetrical d i p h o ~ p h e n e .The ~ ~ ~ chemistry of diphosphenes bearing complexed metallo-substituentshas also received further

[ B ~ ~ P = P - P B ~3' ~ (260)

(259)

A/

P

Ar-P=P F3C (261) Ar = 2,4,6-But&H2

'LAr

Activity in the phospha-alkene area has also continued, but perhaps not at quite the level of recent years. The bis(phospha-alkene) (262) has been prepared, and its coordination chemistry studied.439 A route to the 4,8-diphospha-sindacene (263) has been developed. This compound displays an intense turquoise colour in solution, but is decolorised rapidly in the presence of traces of water.440 In the presence of DBU, the butadiynylphosphines (264) undergo a basecatalysed heteropropargylic rearrangement to give the 1,6-diphosphatetraenes (265), which then undergo a stereoselective valence isomerisation to give the diphosphinidenecyclobutene system (266).441 In the presence of dimethyl acetylenedicarboxylate, the latter system is converted to the 1,Cdiphosphadihydropentalen system (267).442Iodine-induced E/Z-isomerisation about the P=C bonds of (266; R=SiMe3)has been observed.443The phospha-alkene (268) has been shown to undergo copper-mediated coupling to form the diphosphabutadiene (269), in which the terminal aryl substituents at phosphorus are almost perpendicular to the diphosphabutadiene system.444Routes to the new phospha-alkenes (270) have been d e v e l ~ p e d . The ~ ~ *reaction ~ of monolithiophenylphosphide

38

Organophosphorus Chemistry

(264) Ar = Ph or 2,4,6-But3C6H2

(265)

Ar-h: Me02C

+-R Ar

Ar-P

(266) R = H

R

(267)

(268) Ar = 2,4,6-Bu$C6H2

(269)

(270) R’ = 1-Adamantyl or SiMe3 R2 = Cyclopropyl or But

with acetonitrile provides a simple route to the 1 -aza-3-phospha-allyl system (271),protonation of which gives the phospha-alkene (272).447Phospha-alkenes are believed to be involved as intermediates in the reaction of methylphosphine with Ti+ in the gas phase, which eventually leads to the formation of oligomeric inorganic phosphorus compounds.448Attempts to prepare the ylidylphosphaalkene system (273) afforded a series of cyclooligomers.449Various theoretical approaches to aspects of phospha-alkene chemistry have appeared.450*453 The Pchlorophospha-alkene (274)has been the starting point for the synthesis of new systems. It has been shown to act as a powerful enophile building block in its reactions with alkenes, providing a general route to P,y-unsaturated chlorophosp h i n e ~ . ~It’ ~also provides a route to the 2,3,4-triphosphapentadienide system (275), an intermediate for the synthesis of heterocyclic phosphorus comp o u n d ~ .The ~ ~ photoelectron ~ spectra of (274) (and its bromo- and iodoMe Ph-PeNHLi’

Ph-P=C:

CI, Ph3P=C=PX

SiMe3 P=C(

NH2 (2711

(272)

SiMe3 (273) X = CI or Br

(274)

analogue) have been s t ~ d i e d . 4Metal-induced ~~ cleavage of the P=C bond of a phospha-keten system has been described,457and the first metal complex of a phospha-aza-allene described.458The chemistry of the C-lithiated phosphaalkenes (276) has been explored. Transmetallation of (276;X=Cl) with magnesium bromide, followed by reaction with ketones, yields the functionalised system (277), whereas the direct reaction of (276;X=SiMe3)with benzophenone provides

I : Phosphines and Phosphonium Salts X

39 A r m P=C ,

ArmP=Cc

Li (276) X = CI, or SiMe3 Ar = 2,4,6-But3C6H2

Ar #P=

C= CPh2

CR'R20H (277)

a new route to the phospha-allene (278).459The chemistry of phospha-alkenes bearing complexed transition-metal substituents at phosphorus has remained an active area. Hydrometallation of the phospha-alkyne Bu'C =P using a ruthenium hydride complex gives the simple phospha-alkene system (279) which can be reversibly protonated to give the P-complexed system (280).460Further development of Diels-Alder cycloaddition reactions of P-metallophospha-alkeneshas occurred,461and a number of other synthetic transformations r e p ~ r t e d . ~The ~*s~~~ applications of both P-metallo- and C-metallo-phospha-alkenes as building blocks in preparative chemistry have also been reviewed.466

(279)

(280)

c'

Recent progress in the chemistry of phospha-silenes, containing the P=Si link, and the related arsa-silenes, has been reviewed.467Further examples of these systems have been prepared, and their reactivity s t ~ d i e d . Studies ~ ~ ~ ,of~ the ~ structure470 and r e a ~ t i v i t f ~ofl ~ iminophosphenes ~~~ have also continued. Evidence for the transient formation of the arylphosphinidene oxide system, ArP=O, is provided by the pyrolysis of the cyclic anhydride (281), which results in the formation of the secondary phosphine oxide (282).474An improved technique for the thermal fragmentation of the cyclic trimers (283), to give the arylphosphenite system, Ar-0-P=O, has been developed.475The first resonancestabilised, monomeric, ylidylphosphinidene chalcogenides (284), and their related dichalcogenido-h5-derivatives,none of which contain bulky or intramolecularly coordinating substituents, have been prepared, and their reactivity in~estigated.~~~~~~~ Activity in the phospha-alkyne area has again continued at a high level. The applications of these compounds as building blocks in inorganic and organoOAr

Ar-P,

lox:

o'

I ,p

I

4

\ = /

0

0

A&pLOHp,

I

ButOAr

0

(281) Ar = 2,4,6-But&~H2

(282)

(283)

Ar = QR But

R = Me, But or OMe

40

Organophosphorus Chemistry R

(284) R = Me, Et, Ph, mtolyl, or 2,6-C&H3 X = S or Se

metallic ~hemistry,4'~and as a starting point for the synthesis of phosphoruscarbon cage compounds$80 have been reviewed. The chemistry of related arsaalkynes has also shown considerable development in recent years, and this area has now been reviewed.481The first example of the cyclodimerisation of an arsaalkyne has been The enophilic properties of phospha-alkynes have received much attention in the past year, and this topic has attracted the attention of the theoretician^.^^^ A range of polycyclic phosphorus cage systems containing diphosphirane and phosphirane sub-units, e.g., (285), has been obtained from the reactions of Bu'C=P with dienes, under pressure.484Tandem ene reactions of phospha-alkynes with terminal alkenes have provided a route to some new allylic phosphines, e.g., (286).485 Cycloaddition reactions of phospha-alkynes with tropone have provided new phosphorus cage systems, e.g., (287),486the reactivity of which has also been st~died.4~' Phosphorus cage compounds have also been

qR3R4 R'

R2

p/p-

(285) R', R2 = H or alkyl R3, R4 = H, Me, C02Me OSiMe3 or P(O)(OMe)2

(286) R = But, Me2CEt or 1-Adamantyl

(287) R = But or 1-Adamantyl

isolated from the reactions of phospha-alkynes with phosphinidene The cyclic trimer (288) has been isolated from the reaction of Bu'C = P with water in the presence of trifluoroacetic acid.489In contrast, the spirocyclotrimer (289) is the initial product from the reactions of phospha-alkynes with Lewis acids, which lead to new phosphaheterocyclic systems via the intermediacy of the Dewar phosphabenzene system (290).490*491 Phospha-alkynes have also been shown to undergo protonation at carbon when treated with protic superacids, e.g., fluorosulfonic acid, to form initially the phosphavinyl cations (291), which are

I: Phosphines and Phosphonium Salts

41

then trapped by the appropriate anion to form new phospha-alkenes, e.g., (292).491In a similar vein, the related reactions with a protic phosphonium cation lead to the P-phosphonio-substituted phospha-alkene system (293).492Phosphaalkynes have been shown to add to azaphosphirenes, complexed to a metal acceptor, to form the first examples of the trans-l,2-dihydro-l,2,3-triphosphete system (294).493This system is also formed in the reactions of phospha-alkynes with the ylide Me3P=PCF3,494The ring system (295)is formed in the reaction of Bu'C=P with a dithiazyl salt.495 Studies of the coordination chemistry of H

H R*p+

R>=p\ X

(291) R = But or 1-Adamantyl

(292) X = OS02F or -0Tf

(294) R = But or Pr'(Me3Si)N

H )=Po R

6 Ph3

-0Tf

(293) R = l-Adamantyl

(295)

phospha-alkynes have c o n t i n ~ e d Of . ~ particular ~ ~ ~ ~ ~ interest ~ are the cyclooligomerisation reactions which phospha-alkynes may undergo at appropriate transition metal acceptor sites, leading to the formation of, e.g., diphosphacyclob u t a d i e n e ~ , ~1,3,5-triphosphabenzenes, ~>~~~ 1,3,5-Dewar triphosphabenzene, 1,3,5,7-tetrapho~phabarralenes,~~~ and tetraphosphabishomoprismanes.503~5~ Other metal promoted reactions have also been r e p ~ r t e d . ' ~The ~ *chemistry ~~~ of P EC-OH and its metal salts has also seen further d e v e l ~ p m e n t . ~ ~ ~ ~ ~ ~ ~ Significant activity in the chemistry of phosphenium ions, R*P:+ and phosphinidenes RP: is also evident. The reactivity of diaminophosphenium cations has received further a t t e n t i ~ n , ~ ' ~ and * ~ ' *the first example of crystallographically defined system has appeared.513A structural study of the salt (296) has also been reported, confirming the presence of a phosphorus-carbon sigma bond. This compound exhibits the largest downfield 31P chemical shift yet to be observed (ti31P = 500 ppm), and the signal appears as a 1:l:l triplet due to coupling to the quadrupolar 14N nucleus, providing a very rare example of 31P-14Ncoupling.514 The reactivity of phosphenium ions coordinated to transition metals has also received further study.s A theoretical comparison of phosphenium cations 59520

Organophosphorus Chemistry

42

and related anions has appeared.521As usual, the chemistry of phosphinidenes is dominated almost exclusively by that of their metal complexes. A new type of phosphinidene metal complex has been ~ h a r a c t e r i s e d .Phosphinidene ~~~ complexes are believed to be intermediates in the dehydrocyclooligomerisation of primary phosphines, forming mainly cyclopentaphosphines (RP)s in the presence of a zirconium hydride complex.523Two groups have noted the formation of phosphirane systems via the addition of complexed phosphinidene units to carbon-carbon double bonds.524*52s The phosphametallacyclobutenesystem (297) is formed reversibly in the addition of a zirconium-phosphinidenecomplex with disubstituted a l k y n e ~ Zirconium-phosphinidene .~~~ complexes have also been shown to react with carbonyl compounds to form phospha-alkenes, and with phenylisocyanate to form the RP=C=NR system,527and also to be trappable by other reagents.528A free phosphinidene may be involved in the reaction of tri-tbutylcyclotriphosphine with a mixture of a phosphorus trihalide and a tin(I1) halide, which results in insertion of ‘PX’ into the three-membered ring to give the functionalised monohalogenocyclotriphosphine (298).529Solid state NMRS3Oand theoretical studies531of phosphinidenes and their complexes have also appeared. Ar

(296)

(297) Ar = 2,4,6-But3C6H2 R = Me or Ph

(298)

New approaches for the generation of reactive a3-k5 p,-bonded phosphorus compounds have been developed, and the systems (299)532and (300)533characterised by trapping experiments. Evidence for the involvement of the alkylideneoxophosphorane (301) has been adduced from studies of nucleophilic substitution reactions on a 9-fluorenylphosphonamidicchloride, which appear to

0 EtZN-P’ *CH,

0 EtO--P// *S

(299)

proceed via an addition-elimination m e ~ h a n i s mThe . ~ ~arylmetaphosphate (302) is believed to be a key intermediate in the oxidation of some diphosphenes, undergoing self-trapping to form the cyclic system (303).535 The thioxophosphorane (304) has been shown to exist in equilibrium with the valence isomer (305), the two being interconvertible on heating or by p h o t o l y s i ~Treatment .~~~ of the bis(methy1ene)phosphorane (306) with butyllithium leads to the formation of the phosphirene (307).537The 1’-phospha-alkyne system R2P =CSiMe3 has been

I : Phosphines and Phosphonium Salts

43

\

S

I

P-P,

Ar/

Ar

NHR

(303)

(302) Ar = 2,4,6-BUt3C6H2

R

*CR2

R (307)

&

R2P=P

Ar-P(

(306) A t = 2,4,6-But&H2 R = Me3Si

Ph2C-PAr \ I S

(304) (305) Ar = 2,4,6-But3C6H2

CCl2 Ar-PI’/

====

Ph2C=6(

Me3Si

(308) R = Pr‘2N

shown to undergo [2+2] cycloaddition with the h3-system ButC=P to form the stable 1h’, 2h3-diphosphetesystem (308).538 6

Phosphirenes, Phospholes and Phosphinines

A new approach to the synthesis of l-chlorophosphirenes is afforded by the reaction of the phosphirane complex (309), presumably acting as a source of a phosphinidene, with disubstituted alkynes to give the complexed P-aminophosphirenes (310), which, on treatment with hydrogen chloride, are converted to the related complexed 1-chlorophosphirenes (3 11). A key step is their selective

decomplexation using d i p h o ~ Heating . ~ ~ ~ the complexed azaphosphirene (312) with alkynes in toluene solution gives the phosphirenes (313), again via a phosphinidene intermediate.540 The phosphirene (314) has been shown to undergo ring-opening via P-C cleavage in the presence of a ruthenium carbonyl complex.”’ Treatment of the diphosphirenium salt (315 ) with a palladium(0) complex results in the formation of the first example of a diphosphametallocyclobutene (3 16).542 The influence of the heteroatom on the structure of a series of dinaphtho-fused five membered potentially aromatic ring systems (3 17), including the phosphorus and arsenic systems, has been studied by crystallographic technique^.^^ A theoretical study has shown that the incorporation of two c?,h3-phosphorus atoms into the phosphole ring system decreases the ring strain and significantly lowers the inversion barrier about the phosphole pyramidal phosphorus.w Pyramidalisation at phosphorus in phospholes has been shown to increase on

44

Organophosphorus Chemistry Ph

R‘

P Ph (313) R’ = H or C02Me R2 = OEt or C02Me

(314)

(315)

(317) E = NH, 0, S,PPh or AsPh

introduction of alkynyl substituents into the 2- and 5-positions of the ring, these substituents appearing to switch off delocalisation in the phosphole system. Access to such alkynylphospholes, e.g., (318), is afforded by the reactions of related 2-lithiophospholes with alkynes bearing p-toluenesulfonyl s u b ~ t i t u e n t s . ~ ~ ~ A twenty-four membered ring macrocyclic system has been obtained from the reaction of the functionalised biphosphole (319)with o-xylylidenebis(tributy1phosp h ~ r a n e ) .Several ~ ~ ~ groups have reported the results of Diels-Alder type addition reactions to phospholes. The sulfinyl-substituted bicyclic phosphine (320), which contains three carbon, one phosphorus, and a sulfur stereogenic centre, has been obtained, as a palladium complex, from the reaction of l-phenyl-

OHC Ph

Ph

Ph

(318) R = Ph or SiMe3 X = H, Br or CECph

3,4-dimethylphosphole with divinylsulfoxide, in the presence of a chiral aminepalladium complex.547A related addition of an alkynylphosphonamide, via an intermediate 2H-phosphole, is the key step in the synthesis of the water-soluble phosphine (321).548A simple route to the novel enantiomerically pure P-chiral phosphine (322), containing a tertiary amide function, is provided by the addition of N,N-dimethylacrylamide to a chiral amine-palladium-phospholecomplex.549 A wide range of cycloaddition and related products has been observed in the thermal selfcoupling reactions undergone by 1-phenyl-3,4-dimethylphosphole in the presence of p a l l a d i ~ m ( I I ) .A~ ~solid ~ state 31P NMR study of dibenzophosphole, its chalcogenides, and some metal complexes, has been reported.551 Interest in the chemistry of polyphospholes and their related anions has continued. The first example of the 1,2,4-triphosphole system (323; R=CH(SiMe3)2)has been obtained by treatment of a previously described alkali metal 1,2,btriphospholide

I : Phosphines and Phosphonium Salts

45

..

Ph

I

R

Me-

salt with bromobis(trimethylsilyl)methane.552 The above system is found to undergo a 1,3-sigmatropic rearrangement to form the bicyclic system (324), and the energetics of this process have been studied by theoretical techniques.553 Further progress in the chemistry of metal complexes of phospholide anions has been reported. Of particular note is the ‘kalocene’ structure (325) in which potassium ions are sandwiched between phospholide anions,554and the vanadium(I1) polyphospholide sandwich structure (326), containing both 1,3-diphospholide and 1,2,4-triphospholide anions, isolated from the reaction of the

+

A

2-

P n P

2K‘

L

(325)

phospha-alkyne Bu‘C =P with vanadium in the vapour phase.555 Further phosphaferrocenes have been described, and their properties s t ~ d i e dand , ~a~ ~ ~ ~ ~ series of triple-decker diruthenium complexes involving bridging 1,2,4-triphospholyl and 1-arsa-3,4-diphospholylanions c h a r a c t e r i ~ e dNew . ~ ~ ~routes to benzaazaphospholes, e.g., (327), have been d e v e l ~ p e d . ~The ~ ~ *tris(triaza~~ phospho1e)system (328) has been obtained from the 1,3-dipolar tris cycloaddition of t-butylphospha-acetylene to 2,4,6-triazido-3-chlor0-5-~yanopyridine.~~~ The general reactivity of 1,2,3- and 1,2,4-diazaphospholes has received further study. 5623563

OMe

Organophosphorus Chemistry

46

A theoretical approach has been used to compare the proton affinities of phospha-, arsa-, and stiba-benzenes with that of pyridine, and other simpler organo-group 15 system^.'^ The electronic excitation spectra of pyridine and phosphabenzene have also been studied by theoretical methods.s6s A route to the 2chlorophosphorin (329) is offered by the Diels-Alder reaction of 1-vinylnaphthalene with the phospha-alkene ClP=CC12, generated in situ from the reaction of dichloromethyldichlorophosphine with trieth~larnine.~~~ There has been considerable interest in the substitution reactions of 2-halophosphinines. Mathey’s group has established the replacement of a 2-bromo substituent by a phospholide anion, to give, e.g., (330),567by triethylborohydride followed by iodine to give 2-ethylphosphinine~,~~* and by phosphorus tribromide followed by reduction with tris(2-~yanoethylphosphine), to give, e.g., (331). Despite the presence of the o2P atom, it is possible to carry out most of the classical reactions of the dihalogenophosphine substituent. Thus, e.g., the reaction of (331) with Me

Me

(329)

(330)

diphenylacetylene in the presence of aluminium trichloride, followed by reduction, yields the 2-phosphirenylphosphinine (332). The phosphinine nucleus of (331) also withstands electrophilic conditions.s69 Bickelhaupt’s group has developed a route to 2-iodophosphinines and their pentacarbonyltungsten complexes. Whereas attempted lithiation of the free iodophosphinine system failed, the corresponding complexes were lithiated successfully with butyllithium at - 100 “C.In contrast, the free iodophosphinines readily formed organo zinc reagents, whereas the complexed systems did not.570The reactivity of the zinc reagents has also been explored.571A ‘microreview’ of the synthesis and coordination chemistry of phosphorus analogues of 2,2’-bipyridine, e.g., (333), has appeared,572and further studies of the coordination chemistry of phosphines Interest in the chemistry of h5-phosphinines has also cont i n ~ e d . New ’ ~ ~ routes ~ ~ ~ to ~ 1,2h5-azaphosphinines,and a 1,3-)cs-diphosphinine (334), have been d e v e l ~ p e d . ~ ~ ~ ~ ~ ~ ~ Me

(332)

(333)E = N or P R = H or Me

(334)R = NMe2

1: Phosphines and Phosphonium Salts

47

References 1. 2. 3. 4. 5.

6. 7. 8. 9. 10.

11. 12. 13. 14. 15.

16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.

A. J. Zapata and A. C. Rondon, Org. Prep. Proced. In?., 1995,27,567. Y. Uchida, M. Okabe, H. Kobayashi, and S. Oae, Synthesis, 1995,939. D. B. Grotjahn and C. Joubran, Organometallics, 1995,14,5171. 0. Desponds and M. Schlosser,J. Organomet. Chem.. 1996,507,257. 0 .Desponds and M. Schlosser, Tetrahedron Lett., 1996,37,47. M. Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer, P. W. N. M. van Leeuwen, K. Goubitz, and J. Fraanje, Organometallics, 1995,14, 3081. W. A. Herrmann, C. W. Kohlpaintner, R. B. Manetsberger, H. Bahrmann, and H. Kottman, J Mol. Catal. A: Chemical, 1995, W,65. U. Berens, J. M. Brown, J. Long, and R. Selke, Tetrahedron: Asymmetry, 1996, 7, 285. H. Brunner and J. Berghofer, Z. Naturforsch., B: Chem. Sci., 1995,50, 1510. H. Luo and C. Orvig, Can. J. Chem., 1996,74,722. A. Kless, R. Kadyrov, A. Boerner, J. Holz, and H. B. Kagan, Tetrahedron Lett., 1995,36,4601, Y. Hayashi, H. Sakai, N. Kaneta, and M. Uemura, J. Organomet. Chem.. 1995,503, 143. S. D. Perera and B. L. Shaw, Inorg. Chim. Acta, 1995,236,7. D. Enders, T. Berg, G. Raabe, and J. Runsink, Helv. Chim. Acta, 1996,79, 118. H. A. Mayer, P. Stossel, R. Fawzi, and M. Steimann, Chem. Ber., 1995,128,719. H. B. Kagan, P. Diter, A. Gref, D. Guillaneux, A. Masson-Szymczak, F. Rebiere, 0. Riant, 0. Samuel, and S. Taudien, Pure Appl. Chem., 1996,68,29. R. J. Delang, J. Vansoolingen, H. D. Verkruijsse, and L. Brandsma, Synth. Commun., 1995,25,2989. W. Zhang, Y. Adachi, T. Hirao, and I. Ikeda, Tetrahedron:Asymmetry, 1996,7,451. Y. Nishibayashi, K. Segawa, K. Ohe, and S. Uemura, Organometallics, 1995, 14, 5486. C. J. Richards and A. W. Mulvaney, Tetrahedron:Asymmetry, 1996,7,1419. J. Park, S. Lee, K. H. Ahn, and C-W. Cho, TetrahedronLett., 1995,36,7263. A. Mernyi, C. Kratky, W. Weissensteiner, and M. Widhalm, J. Organomet. Chem., 1996,508,209. G. Kutschera, C. Kratky, W. Weissensteiner, and M. Widhalm, J. Organomet. Chem.. 1996,508,195. A. Ohno, S.Yamane, and T. Hayashi, Tetrahedron:Asymmetry, 1995,6,2495. T. Hayashi, C. Hayashi, and Y. Uozumi, Tetrahedron:Asymmetry, 1995,6,2503. A. Massonszymczak, 0. Riant, A. Gref, and H. B. Kagan, J. Organomet. Chem., 1996,511,193. C. Ganter and T. Wagner, Chem. Ber., 1995,128,1157. Y . Nishibayashi, Y. Arikawa, K. Ohe, and S . Uemura, J. Org. Chem., 1996, 61, 1172. H. C. L. Abbenhuis, U. Burckhardt, V. Gramlich, A. Martelletti, J. Spencer, I. Steiner, and A. Togni, Organometallics, 1996,15, 1614. G. Iftime, C. Moreau-Bossuet, E. Manoury, and G. G. A. Balavoine, Chem. Commun., 1996,527. C . H. Honeyman, D. A. Foucher, F. Y. Dahmen, R. Rulkens, A. J. Lough, and 1. Manners, Organometallics, 1995,14,5503. K. Toyota, M. Shibata, and M. Yoshifuji, Bull. Chem. Soc. Jpn., 1995,68,2633. S . Yan, Y. Zhao, and K. Zhou,Huaxue Shiji, 1995,17,167 (Chem. Abstr., 1996,124, 8901). A. Saare and I. Dahlenburg, 2.Natuforsch., B: Chem. Sci., 1995,50,1009. A. Terfort and H.Brunner, J. Chem. SOC.Perkin Trans. 1,1996,1467. M. Mina-Aghayan, R. Boukherroub, G. Etemad-Moghadam, G. Manuel, and M. Koenie. TetrahedronLett.. 1996.37.3109.

48

Organophosphorus Chemistry

37. 38.

P. B. Hitchcock, M. F. Lappert, W-P. Leung, and Ping Yin, J. Chem. Suc., Dalton

39.

40. 41.

H. C. Aspinall and M. R. Tillotson, Inorg. Chem., 1996,355. Trans., 1995,3925. M. Driess, S. Rell, H. Pritzkow, and R. Janoschek, Chem. Commun., 1996,305. L. McKinstry and T. Livinghouse, Tetrahedron, 1995,51,7655. S . Yamago, M. Yanagawa, H. Mukai, and E. Nakamura, Tetrahedron, 1996, 52, 5091.

42. 43.

H. Ding, B. E. Hanson, and J. Bakos, Angew. Chem., Int. Ed. Engl., 1995,34,1645. C. Wiesauer, C. Kratky, and W. Weissensteiner, Tetrahedron: Asymmetry, 1996, 7 ,

44.

49. 50.

Y. Kataoka, Y. Saito, K.Nagata, K.Kitamura, A. Shibahara, and K. Tani, Chem. Lett., 1995,833. J. Holz, A. Borner, A. Kless, S. Borns, S. Trinkhaus, R. Selke, and D. Heller, Tetrahedron: Asymmetry, 1995,6, 1973. M. Watanabe, Tetrahedron Lett., 1995,36,8991. J-C. Shi, M-C. Hong, D-X. Wu, Q-T. Liu, and B-S. Kang, Chem. Lett., 1995,685. M. A. Brown, P. J. Cox, R. A. Howie, 0. A. Melvin, 0. J. Taylor, and J. L. Wardell, J. Organornet. Chem.. 1995,498,275. S . R. Gilbertson and C-W. T. Chang, J. Org. Chem., 1995,60,6226. G. Kniihl, P. Sennhenn, and G. Helmchen, J. Chem. SOC.,Chem. Commun., 1995,

51.

T. Minami, Y. Okada, T. Otaguro, S. Tawaraya, T. Furuichi, and T. Okauchi,

52.

Tetrahedron: Asymmetry, 1995,6,2469. F. Jakle, M. Mattner, T. Priermeier, and M. Wagner, J. Organornet. Chem., 1995,

397. 45. 46. 47. 48.

1845.

502,123. 53. 54. 55. 56. 57. 58. 59.

U. Heim, H. Pritzkow, U. Fleischer, H. Grutzmacher, M. Sanchez, R. Reau, and G. Bertrand, Chem. Eur. J., 1996,2,68. E. Valls, J. Suades, B. Donadieu, and R. Mathieu, Chem. Commun., 1996,771. Yu. A. Veits, E. G. Neganova, and I. P. Beletskaya, Zh. Org. a i m . , 1995, 31, 794 (Chem. Abstr., 1996,124,232 602. S.T. Liu, C-H. Yieh, and H-P. Dai, Proc. Natl. Sci. Counc., Repub. China, Part A: Phys. Sci. Eng., 1995,19,1 (Chem. Abstr., 1995,123,33171). G. Reinhard, R. Soltek, G. Huttner, A. Barth, 0. Walter, and L. Zsolnai, Chem. Ber., 1996,129,97. T. Seitz, A. Muth, and G. Huttner, 2. Naturjbrsch., B: Chem. Sci., 1995, 50, 1045; T.Seitz, A. Asam, G. Huttner, 0.Walter, and L. Zsolnai, 2.Naturforsch., B: Chem. Sci.. 1995,50, 1287. J. Scherer, G. Huttner, and M. Buchner, Chem. Ber.. 1996, 129, 697; A. Borner, A. Kless, R. Kempe, D. Heller, J. Holz, and W. Baumann, Chem. Ber., 1995, 128, 767.

60. 61. 62. 63.

64. 65.

66.

A. Weisman, M. Gozin, H-B. Kraatz, and D. Milstein, Inorg. Chem., 1996,35, 1792. Q. Jiang, D. van Plew, S.Murtuza, and X . Zhang, Tetrahedron Lett., 1996,37,797. A. Buhling, J. W. Elgersma, S. Nkrumah, P. C. J. Kamer, and P. W. N. M. van Leeuwen, J. Chem. SOC.,Dalton Trans., 1996,2143. M. Peer, J. C. de Jong, M. Kiefer, T. Langer, H. Rieck, H. Schell, P. Sennhenn, J. Sprinz, H. Steinhagen, B. Wiese, and G. Helmchen, Tetrahedron,1996,52,7547. L. D. Field and I. P. Thomas, Inorg. Chem., 1996,35,2546. A. G. Avent, P. B. Hitchcock, M. F. Lappert, and P. Yin, J. Chem. SOC.,Dalton Trans., 1995,2095. P. Wimmer, and M. Widhalm, Phosphorus, Sul$ur, Silicon, Relat. Elem., 1995, 106, 105.

67. 68. 69.

D. C. R. Hockless, Y.B. Kang, M. A. McDonald, M. Pabel, A. C. Willis, and S . B. Wild, Organometallics,1996, 15, 1301. H. Fujihar, T. Nishioka, H. Mima, and N. Furukawa, Heterocycles, 1995,41,2647. A. Moezzi, M. M. Olmstead, D. C. Pestana, and P. P. Power, Z. Anorg. Allg. Chem., 1995,621,1933.

I : Phosphines and Phosphonium Salts 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102.

49

W. Wolfsberger, J. Bank, and H. Werner, 2. Naturforsch., B: Chem. Sci., 1995, 50, 1319. G. Becker, K. Huebler, M. Niemeyer, N. Seidler, and B. Thinus, 2. Anorg. Allg. Chem., 1996,622,197. A. Bassowa, I. Kovacs, E. Matern, E. Sattler, and G. Fritz, 2.Anorg. Allg. Chem., 1996,622,931. I. Kovacs, E. Matern, and G. Fritz, 2. Anorg. Allg. Chem., 1996,622,935. H. Schmidbaur and A. Bauer, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995, 102, 217. M. Westerhausen, M. Hartmann, and W. Schwarz, Inurg. Chem., 1996,35,2421. B. Riegel, A. Pfitzner, G. Heckmann, and H. Binder, 2. Anorg. Allg. Chem., 1995, 621,1989. M. Walz, M. Nieger, D. Gudat, and E. Niecke, 2.Anorg. Allg. Chem., 1995, 621, 1951. M. Driess, H. Pritzkow, and M. Reisgys, Chem. Ber., 1996,129,247. H. Schumann and M. Schaefers, 2.Anorg. Allg. Chem., 1996,622, 571. G. Chelucci, M. A. Cabras, C. Botteghi, C. Basoli, and M. Marchetti, Tetrahedron: Asymmetry, 1996,7,885. P. G. Manzo, S.M. Palacios, R. A. Alonso, and R. A. Rossi, Org. Prep. Proced. Int., 1995,27,660. G. S . Foray, A. B. Penenory, and R. A. Rossi, J. Phys. Org. Chem., 1995,8,356. E. C. Ashby and A. K. Deshpande, J. Org. Chem., 1995,60,7117. T. Suzuki, K.Kashiwabara, and J. Fujita, Bull. Chem. SOC.Jpn., 1995,68, 1619. E. T. Singewald, C. A. Mirkin, and C. L. Stern, Angew. Chem., Int. Ed Engl., 1995, 34, 1624. C. Bianchini, P. Frediani, and V.Sernau, Organometallics, 1995,14, 5458. N. K. Gusarova, S. I. Shaikhudinova, V. I. Dmitriev, S. F. Malysheva, S. N. Arbuzova, and B. A. Trofimov, Zh. Obshch. Khim., 1995, 65, 1096 (Chem. Abstr., 1996,124,146 287). D. Bongert, G. Heckmann, W.Schwarz, H. D. Hausen, and H. Binder, 2.Anorg. Allg. Chem., 1995,621, 1358. B. Riegel, G. Heckmann, H. D. Hausen, W. Schwarz, H. Binder, E. Fluck, S. Grundei, H. Noth, M. Schmidt, M. L. McKee, A. Dransfeld, and P. von R. Schleyer, 2.Anorg. Allg. Chem., 1995,621,1111. Y. B. Kang, M. Pabel, D. D. Pathak, A. C. Willis, and S . B. Wild, Main Group Chem., 1995,1,89. R. J. Wehmschulte and P. P. Power, J. Am. Chem. Soc., 1996,118,791. L. K.Krannich, C.L. Watkins, and S . J. Schauer, Organometallics, 1995,14,3094. D. A. Atwood, A. H. Cowley, R. A. Jones, R. J. Powell, and C. M. Nunn, Organometallics, 1996,15,2657. D. Wiedmann, H. D. Hausen, and J. Wiedlein, 2. Anorg. Allg. Chem., 1995, 621, 1351. F. M. Elms, G. A. Koutsantonis, and C . L. Raston, J. Chem. Suc., Chem. Commun., 1995,1669. R. L. Wells, S. R. Aubuchon, M. S. Lube, and P. S. White, Main Group Chem., 1995, 1,81. R. L. Wells, R. A. Baldwin, P. S. White, W. T. Pennington, A. L. Rheingold, and G. P. A. Yap, Organometallics, 1996,15,91. G. H. Robinson, J. A. Bums, and W. T. Pennington, Main Group Chem.. 1995, 1, 153. 0. T. Beachley, J. D. Maloney, M. A. Banks, and R. D. Rogers, Organometallics, 1995,14,3448. M. Driess, R. Janoschek, H. Pritzkow, S. Rell, and U. Winkler, Angew. Chem., Int. Ed Engl., 1995,34,1614. G. W. Rabe, J. Riede, and A. Schier, Inorg. Chem., 1996,35,2680. S. Atlan, F. Nief, and L. Ricard, Bull. Soc. Chim. Fr., 1995, 132,649.

50

Organophosphorus Chemistry

103. P. G. Edwards, J. S. Parry, and P. W.Read, Organometallics,1995,14,3649. 104. G. I. Nikonov, L. G. Kuzmina, P. Mountford, and D. A. Lemenovskii, Organometallics, 1995,14,3588. 105. S . Challet, J. C. Leblanc, and C. Moise, New J. Chemistry, 1995, 19, 1139. 106. P. Sauvageot, andC. Moise, Bull. Soe. Chim. Fr., 1996,133, 177. 107. W. Malisch, K. Hindahl, K. Grun, W. Adam, F. Prechtl, and W. S . Sheldrick, J. Organomet. Chem., 1996,509,209. 108. E.Hey-Hawkins, and K. Fromm, Polyhedron, 1995,14,2825. 109. E. Lindner, W.Kneissle, R. Fawzi, M. Steimann, H. A. Meyer, and K. Gierling, Chem. Ber., 1995,128,973. 110. F. Lindenberg, J. Sieler, and E. Hey-Hawkins, Polyhedron, 1996,15, 1459. 111. A. Cano, T. Cuenca, M. Galakhov, G. M. Rodriguez, P. Royo, C. J. Cardin, and M. A. Convery, J. Organomet. Chem., 1995,493,17. 112. M. C. Fermin, J. Ho, and D. W. Stephan, Organometallics,1995,14,4247. 113. M. G. Davidson, A. J. Edwards, M. A. Paver, P. R. Raithby, C. A. Russell, A. Steiner, K. L.Verhorevoort, and D. S . Wright, J. Chem. Soe., Chem. Commun., 1995,1989. 114. H. H. Karsch, Zzv. Akad. Nauk. Ser. Khim., 1993, 2025 (Chem. Abstr., 1995, 121, 331 12). 115. H. H. Karsch, R. Richter, A. Schier, M. Heckel, R. Ficker, and W. Hiller, J. Organomet. Chem., 1995,501, 167. 116. S . Herold, A. Mezzetti, L. M. Venanzi, A. Albinati, F. Lianza, T. Gerfin, and V. Gramlich, Znorg. Chim. Acta, 1995,235, 2 15. 117. R. A. Gossage, G. D. McLennan, and S . R. Stobart, Znorg. Chem., 1996,35,1729. 118. P. Braunstein, R. Hasselbring, A. DeCian, and J. Fisher, Bull. Soc. Chim. Fr., 1995, 132,691. 119. N. K. Gusarova, S. F. Malysheva, S. N. Arbuzova, L. Brandsma, and B. A. Trofimov, Zh. Obshch. Khim., 1994,642062 (Chem. Abstr., 1995,123,83463). 120. N. K. Gusarova, S. N. Arbuzova, S. F. Malysheva, M. Ya. Khil'ko, A. A. Tatarinova, V. G. Gorokhov, and B. A. Trofimov, Izv. Akad Nauk, Ser. Khim., 1995,1597 (Chem. Abstr.. 1996,124, I17 430). 121. Ya. A. Dorfman, L. V. Levina, and L. I. Grekov, Zh. Obshch. Khim., 1995,65, 1459 (Chem. Abstr., 1996,124,343 469). 122. L.Lavenot, M. H. Bortoletto, A. Roucowr, C. Larpent, and H. Patin, J. Organomet. Chem., 1996,509,9. 123. T. Hayashi, S. Niizuma, T. Kamikawa, N. Suzuki, and Y. Uozumi, J. Am. Chem. Soc., 1995,117,9101. 124. J. Kang, S. H. Yu, J. I. Kim, and H. G. Cho, Bull. Korean Chem. Soc., 1995,16,439. 125. J-M. Valk, T.D. W. Claridge, and J. M. Brown, Tetrahedron: Asymmetry, 1995, 6, 2597. 126. A. Marinetti, C. Le Menn, and L. Ricard, Organometallics,1995,14,4983. 127. M. Sawamura, H. Hamashima, M. Sugawara, R. Kuwano, and Y . Ito, Organometallies, 1995, 14,4549. 128. G. Keglevich, K. Ujszaszy, A. Szollosy, K. Ludanyi, and L. Toke, J. Organornet. Chem., 1996,516,139. 129. E. Bonaplata, H.Ding, B. E. Hanson, and J. E. McGrath, Polymer, 1995,36,3035. 130. J. F. Pilard, G. Baba, A-C. Gaumont, and J-M. Denis, Synlett., 1995, 1168. 131. N. K. Skvortsov and S . V. Toldov, Zh. Obshch. Khim., 1994,64,1784 (Chem. Abstr., 1995,123,83 438). 132. A. Bader, M. Pabel, A, C. Willis, and S . B. Wild, Znorg. Chem., 1996,35,3874. 133. C . Ekkert, L. Dahlenburg, and A. Wolski, 2. Naturforsch., B: Chem. Sci., 1995, 50, 1004. 134. F. J. Feher, J. J. Schwab, S. H. Phillips, A. Eklund, and E. Martinez, Organometallies, 1995,14,4452. 135. S . D. Perera, M. Shamsuddin, and B. L. Shaw, Can. J. Chem., 1995,73,1010. 136. S . D. Perera and B. L. Shaw, J. Chem. SOC.,Dalton Trans., 1995,3861.

I : Phosphines and Phosphonium Salts

51

S. D. Perera, B. L. Shaw, and M. Thorntonpett, Inorg. Chim. Acta, 1995,233, 103. N. Cenac, M. Zablocka, A. Igau, G. Comenges, J-P. Majoral, and A. Skowronska, Organometallics, 1996,15, 1208. 139. A. Kless, J. Holz, D. Heller, R. Kadyrov, R. Selke, C. Fischer, and A. Borner, Tetrahedron: Asymmetry, 1996,7,33. 140. M. Slaney, M. Bardaji, M-J. Casanove, A-M. Caminade, J. P. Majoral, and B. Chaudret, J. Am. Chem. SOC.,1995,117,9764. 141. P. Lange, A. Schier, and H. Schmidbaur, Inorg. Chim. Acta, 1995,235,263. 142. M. Santimaria, T.Maina, U. Mazzi, and M. Nicolini, Inorg. Chim. Actn, 1995, 240, 291. 143. S. R. Gilbertson and X . Wang, J. Org. Chem., 1996,434. 144. S . R. Gilbertson and G. W . Starkey, J. Org. Chem., 1996,61,2922. 145. T. Malmstrom and C. Andersson, Chem. Commun., 1996, 1135. 146. K. D. Behringer and J. Blumel, Chem. Commun., 1996,653. 147. K. D. Behringer and J. Blumel, 2.Naturforsch., B: Chem. Sci., 1995,50, 1723. 148. M. G. L. Petrucci and A. K . Kakkar, J. Chem. SOC.,Chem. Commun., 1995, 1577. 149. G. Markl, M. Reiss, P. Kreitmeir, and H. Noth, Angew. Chem., Int. Ed. Engl., 1995, 34,2230. 150. P. Wimmer, G. Klintschar, and M. Widhalm, Heterocycles, 1995,41,2745. 151. A. R. Muci, K. R. Campos, and D. A. Evans, J. Am. Chem. SOC.,1995,117,9075. 152. F. Lam, K. S. Chan, and B-Ji Liu, Tetrahedron Lett., 1995,36,6261. 153. F. Bitterer, K. P. Langhans, and 0. Stelzer, 2. Naturforsch., B: Chem. Sci., 1995, 50, 1521. 154. R. W. Alder, D. D. Ellis, J. K. Hogg, A. Martin, A. G. Orpen, and P. N. Taylor, Chem. Commun., 1996,537. 155. R. W. Alder, D. D. Ellis, A. G. Orpen, and P. N. Taylor, Chem. Commun., 1996,539. 156. S . J. Coles, P. G. Edwards, J. S. Fleming, M. B. Hursthouse, and S . S . Liyanage, Chem. Commun., 1996,293. 157. R. Schmid, E. A. Broger, M. Cereghetti, Y. Crameri, J. Foricher, M. Lalonde, R. K. Muller, M. Scalone, G. Schoettel, and U. Zutter, Pure Appl. Chem.. 1996,68, 131. 158. G. E. Herberich and S . Moss, Chem. Ber., 1995,128,689. 159. M. Viotte, B. Gautheron, M. M. Kubicki, Y.Mugnier, and R. V. Parish, Inorg. Chem., 1995,34,3465. 160. J. Podlaha, P. Stepnicka, J. Ludvik, and I. Cisarova, Organometallics,1996, 15, 543. 161. I. R. Butler, W. R. Cullen, S. J. Rettig, and A. S. C. White, J. Organomet. Chem., 1995,492,157. 162. S . Hoppe, H. Weichmann, K. Jurkschat, C. Schneider-Koglin, and M. Drager, J. Organomet. Chem., 1995,50563. 163. P. Barbaro and A. Togni, Organometallics, 1995,14,3570. 164. J. Spencer, V. Gramlich, R. Hausel, and A. Togni, Tetrahedron: Asymmetry, 1996,7, 41. 165. A. Albinati, P. S. Pregosin, and K.Wick, Organometallics,1996,15,2419. 166. A. B. Kostitsyn, E. V. Shulishov, M. Regitz, and 0. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 1994,2050 (Chem. Abstr., 1995,123,56062. 167. A. A. Bordachev, M. M. Kabachnik, Z. S. Novikova, and 1. P. Beletskaya, Izv. Akad Nauk, Ser. Khim.. 1994,754 (Chem. Abstr., 1995,123,112 186). 168. M. Baudler and L. Deriesemeyer, 2. Naturjbrsch. B: Chem. Sci., 1996,51, 101. 169. Yu. G. Shtyrlin, N. I. Tyryshkin, G. G. Iskhakova, V. V. Gavrilov, V. D. Kiselev, and A. I. Konovalov, Zh. Obshch. Khim., 1995,65, 1101 (Chem Abstr.. 1996, 124, 146 288). 170. Yu. G. Gololobov and T. 0. Krylova, Heteroat. Chem., 1995,6,271. 171. K-F. Liou and C-H. Cheng, J. Chem. SOC.,Chem. Commun., 1995,1603. 172. K-F. Liou and C-H. Cheng, J. Chem. Soc., Chem. Commun.. 1995,2473. 173. C. Zhang and X . Lu, Synlett, 1995,645. 174. L. A. P. Kane-Maguire, M. Manthey, J. G. Atton, and G. R. John, Inorg. Chim. Acta, 1995,240,71.

137. 138.

52

175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 21 1. 212.

Organophosphorus Chemistry

W. A. Donaldson, L. Shang, M. Ramaswamy, C. A. Droste, C. Tao, and D. W. Bennett, Organometallics,1995,145119. A. S. Balueva, E. R. Mustakimov, and G. N. Nikonov, Zh. Obshch. Khim., 1995,65, 764 (Chem. Abstr., 1996,124,56051). A. S . Balueva, E. R. Mustakimov, G. N. Nikonov, Yu. T. Struchkov, A. P. Pisarevskii, and R. R. Musin, Izv. Akad. Nuuk, Ser. Khim.,1996,183 (Chem. Abstr., 1996,124,343 427). Yu. A. Veits, N. S. Nasonova, N. B. Karlstedt, E. G. Neganova, and I. P. Beletskaya, Zh. Org. Khim..1995,31, 179 (Chem. Abstr., 1996,124, 146 270). W. Wolfsberger, W. Burkart, and H. Werner, 2.Naturforsch., B: Chem. Sci., 1995, 50,937. N. Bricklebank, S. M. Godfrey, H.P. Lane, C. A. McAuliffe, R. G. Pritchard, and J-M. Moreno, J. Chem. SOC.,Dalton Trans., 1995,2421. R. Mazurkiewiczand A. W. Pierwocha, Monatsh. Chem., 1996,127,219. D. Robinson, A. L. Stanley, and S. P. Stanforth, J. Heterocycl. Chem., 1995, 32, 783. A. Espinosa, M. A. Gallo, J. Campos, and J. A. Gomez, Synlett., 1995,1119. P. Frayen, Phosphorus, Su!fiur,Silicon, Relat. Elem.. 1995,102,253. P. Frayen and P. Juwik, Tetrahedron Lett., 1995,36,9555. C. Johnstone, W. J. Kerr, and J. S . Scott, Chem. Commm, 1996,341. I. P. Andrews, R. Bannister, S. K. Etridge, N. J. Lewis, M. V. Mullane, and A. S . Wells, Tetrahedron Lett., 1995,36,7743. T . Imamoto, K. Asakura, H. Tsuruta, K. Kishikawa, and K. Yamaguchi, Tetrahedron Lett., 1996,37, 503. G. Brenchley, M. Fedouloff, M. F. Mahon, K. C. Molloy, and M. Wills, Tetrahedron, 1995,51,10581. T. Imamoto, H. Tsuruta, Y. Wada, H. Masuda, and K. Yamaguchi, Tetrahedron Lett., 1995,36,8271. T. Imamoto, T. Yoshizawa, K. Hirose, Y. Wada, H. Masuda, K. Yamaguchi, and H. Seki, Heteroatom Chem., 1995,6,99. T. Imamoto, E. Hirakawa, Y.Yamanoi, T. Inoue, K. Yamaguchi, and H. Seki, J. Org. Chem., 1995,60,7697. M. L. Kurtzweil and P. Beak, J. A m Chem. Soc., 1996,118,3426. N. Somasundaram and C. Srinivasan, J. Org. Chem., 1996,61,2895. P. Le Maux, H.Bahri, G. Simonneaux, and L. Toupet, Inorg. Chem., 1995,34,4691. W. Adam and S . Weinkoetz, Tetrahedron Lett., 1995,36,7431. X-B. Ma, M. Birkel, T. Wettling, and M. Regitz, Heteroat. Chem., 1995,6, 1. G. Grossman, H. Beckmann, 0. Rademacher, K. Kriiger, and G. Ohms,J. Chem. Soc., Dalton Trans., 1995,2797. T.Besson, K. Emayan, and C. W. Rees,J. Chem. Soc., Perkin Trans. I , 1995,2097. D. L. Hughes and R.A. Reamer, J. Org. Chem., 1996,61,2967. J. S . Fruchtel and G. Jung, Angew. Chem., In?. Ed EngL, 1996,35,17. V. Krchnak, D. Cabel, A. Weichsel, and 2.Flegelova, Lett. Pept. Sci, 1995,1,27. V. Krchnak, Z. Flegelova, A. S.Weichsel, and M. Lebl, TetrahedronLett., 1995,36, 6193. R. M. Valerio, A. M. Bray, and H. Patsiouras, TetrahedronLett.. 1996,37,3019. I. D. Grice, P. J. Harvey, I. D. Jenkins, M. J. Gallagher, and M. G. Ranasinghe, TetrahedronLett., 1996,37, 1087. M. Saady, L. Lebeau, and C. Mioskowski, Synlett., 1995,643. J. A. Dodge, J. S. Nissan, and M. Presnell, Org. Synth., 1996,73, 110. R. J. Cherney and L. Wang, J. Org. Chem.. 1996,61,2544. A. B. Charette, B. C6t6, S. Monroc, and S . Prescott, J. Org. Chem., 1995,60,6888. D. P. Sebesta, S.S.O’Rourke, and W. A. Pieken, J. Org. Chem., 1996,61,361. M. C. Aesa, G. Baan, L. Novak, and C. Szantay, Synth. Commun., 1996,26,909. M. C. Aesa, G. Baan, L. Novak, and C. Szantay, Synth. Commun., 1995,25,2575.

1: Phosphines and Phosphonium Salts

213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247.

53

T. Tsunoda, C. Nagino, M. Oguri, and S . Ito, Tetrahedron Lett., 1996,37,2459. T. Tsunoda, F. Ozaki, N. Shirakata, Y. Tamaoka, H. Yamamoto, and S. Ito, Tetrahedron Lett., 1996,37,2463. K. E. Bell, D. W.Knight, and M. B. Gravestock, Tetrahedron Lett., 1995,36,8681. T. Gajda, M. Nowalinska, S. Zawadzki, and A. Zwierzak, Phosphorus, SulJur, Silicon, Relat. Elem., 1995,105,45. M. J. Di Grandi and J. W. Tilley, Tetrahedron Lett., 1996,37,4327. T. Tsunoda, H. Yamamoto, K. Goda, and S.Ito, Tetrahedron Lett., 1996,37,2457. C. F. Purchase and A. D. White, Synth. Commun., 1996,26,2687. M. Abarghaz, A. Kerbal, and J-J. Bourguignon, Tetrahedron Lett.. 1995,36,6463. T . C. Chien, C. S.Chen, J. Y. Yeh, K. C. Wang, and J. W .Chern, TetrahedronLett., 1995,36,7881. C. D. Hall, P. D. Beer, R. L. Powell, and M. P. Naan, Phosphorus. Sulfur, Silicon, Relat. Elem., 1995,105, 145. G. Alcarez, V. Piquet, A. Baceiredo, F. Dahan, W.W.Schoeller, and G. Bertrand, J. Am. Chem. SOC.,1996,118,1060. D. E. Shalev, S. M. Chiacchiera, A. E. Radkowsky, and E. M. Kosower, J. Urg. Chem., 1996,61,1689. P. Molina, C.Lopez-Leonardo,J. Llamas-Botia,C. Foces-Foces, and C. FernandezCastaiio, J. Chem. SOC.,Chem. Commun., 1995,1387. C . A. M. Afonso, Tetrahedron Lett., 1995,36,8857. C . A. Obafemi, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,104, 1. M. M. Ismail, M. Abdel-Megid, and H. M. El-Shaaer, Znd. J. Heterocycl. Chem., 1995,5,59. V. A. Nikolaev, G. P. Kantin, and P. U. Utkin, Zh. Org. Khim.,1994, 30, 1292 (Chem. Abstr., 1995,123,338 646). T. Mohan, P. Senthiveland M. N. S . Rao, Znd. J. Chem., A:, 1995,34,961. C. A. Fyfe, K. C. Wong-Moon, Y. Huang, and H. Grondey, J. Am. Chem. Soc., 1995,117,10397. T . L. Schull, J. C. Fettinger, and D. A. Knight, J. Chem. SOC.,Chem. Commun., 1995,1487. M. Wada, S. Miyake, S. Hayashi, H. Ohba, S. Nobuki, S. Hayase, and T. Erabi, J. Organomet. Chem., 1996,507,53. B. M. Trost, B. Breit, S. Peukert, J. Zambrano, and J. W. Ziller, Angew. Chem., Znt. Ed. Engl., 1995,34,2386. P.Lange, A. Schier, and H. Schmidbaur,Znorg. Chem., 1996,35,637. B. M. Butin, G. M. Isaeva, R. N. Il’yasov, and K. B. Erzhamov, Zzv. Nuts. Akad Nu&, Resp. Kaz., Ser. a i m . , 1994,68 (Chem. Abstr., 1995,123, 112 165). R. Martens, W. W. du Mont, J. Jeske, P. G. Jones, W. Saak, and S . Pohl, J. Organomet. Chem., 1995,501,251. F. Teixidor, C. Vinas, M. M. Abad, R. Nunez, R. Kivekaes, and R. Sillanpaea, J. Organomet. Chem., 1995,503,193. B. Kaufmann, H. N6th, and R. T. Paine, Chem. Ber., 1996,129,557. M. D. Fryzuk, X.Gao, and S.J. Rettig, Can. J. Chem., 1995,73, 1175. J. R. Goerlich,V.Plack, and R.Schmutzler, J. Fluorine Chem., 1996,76,29. A. S . Balueva, A. A. Karaski, E. I. Ayupova, R. Z. Musin, and G. N. Nikohov, Zh. Obshch. Khim., 1994,64,1792 (Chem. Abstr., 1995,123,83 480). H . Lee and C-H. Jun, Bull. Korean Chem. SOC.,1995,16,66; 1995,16,1135. L. P. Barthel-Rosa, V. J. Catalano, and J. H. Nelson, J. Chem. SOC.,Chem. Commun., 1995,1629. M. Zablocka, A. Igau, N. Cenac, B. Donnadieu, F. Dahan, J. P. Majoral, and M. K. Pietrusiewicz, J. Am. Chem. SOC..1995,117,8083. M. C. Fermin and D.W. Stephan, J. Am. Chem. SOC.,1995,117,12 645. I. V. Komarov, M. Yu. Kornilov, A. A. Tolmachev, A. A. Yurchenko, E. B. Rusanov, and A. N. Chernega, Tetrahedron, 1995,51,11271.

54 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284.

Organophosphorus Chemistry V. V. Dunina and E. B. Golovan, Tetrahedron:Asymmetry, 1995,6,2747. V. V. Dunina, E. B. Golovan, N. S. Gulyukina, and A. V. Buyevich, Tetrahedron: Asymmetry, 1995,6,2731. H. F. Shen, S.G. Bott, and M. G. Richmond, Organometallics, 1995,14,4625. S. Pulst, P. Arndt, W. Baumann, A. Tillack, R. Kempe, and U. Rosenthal, J. Chem. SOC.,Chem. Commun., 1995,1753. D. K. Morita, J. K. Stille, and J. R. Norton, J. Am. Chem. SOC.,1995, 117, 8576. W. A. Herrmann, C. Brossmer, K. Oefele, M. Beller, and H. Fischer, J. Organomet. Chem., 1995,491, C1. W. A. Herrmann, C. Brossmer, K. Oefele, M. Beller, and H. Fischer, J. Mol. Catal. A:, 1995,103, 133. R. S. Drago, Organometallics, 1995,14, 3408. S . T. Howard and J. A. Platts, J. Phys. Chem., 1995,99,9027. R. S . Drago and S. Joerg, J. Am. Chem. SOC.,1996,118,2654. P. B. Karadakov, J. Gerratt, D. L. Cooper, and M. Raimondi, THEOCHEM, 1995, 341, 13. W. W. Schoeller, B. Goette, and U. Tubbesing, J. Phys. Org. Chem., 1995,8,742. P. T. Brain, D. W. H. Rankin, H. E. Robertson, A. J. Downs, T. M. Greene, M. Hofmann, and P. von R. Schleyer, J. Mol. Struct., 1995,352/353, 135. K. Akutsu, M. Ogasawara, M. Saburi, K. Kozawa, and T. Uchida, Bull. Chem. SOC. Jpn., 1996,69, 1223. M. Chauhan, C. Chuit, R. J. P. Corriu, C. Reye, J. P. Declercq, and A. Dubourg, J. Organomet. Chem., 1996,510,173. C. Chuit, R. J. P. Corriu, P. Monforte, C. Reye, J. P. Declercq, and A. Dubourg, J. Organomet. Chem., 1996,511,171. F. Chalier, Y. Berchadsky, J-P. Finet, G. Gronchi, S. Marque, and P. Tordo, J. Phys. Chem., 1996,100,4323. S-Y. Siah, P-H. Leung, K. F. Mok, and M. G. B. Drew, Tetrahedron: Asymmetry, 1996,7, 357. B-H. Aw, S. Selvaratnam, P-H. Leung, N. H. Rees, and W. McFarlane, Tetrahedron: Asymmetry, 1996,7, 1753. P. Zanello, G. Opromolla, G. Giorgi, G. Sasso, and A. Togni, J. Organomet. Chem., 1996,506,41. M. Saraswathi, J. M. Miller, and T. R. B. Jones, Can. J. Chem., 1995,73, 1321. S . Yasui, Rev. Heteroatom Chem., 1995,12, 145. S . Yasui, K. Shioji, M. Tsujimoto, and A. Ohno, Chem. Lett., 1995,783. R. L. Smith, A. Schweighofer, H. Keck, W. Kuchen, and H. I. Kenttama, J. Am. Chem. SOC.,1996,118,1408. P. Dyer, 0. Guerret, F. Dahan, A. Baceiredo, and G. Bertrand, J. Chem. Soc., Chem. Commun., 1995,2339. P. Dyer, A. Baceiredo, and G. Bertrand, Inorg. Chem., 1996,35,46. T. Lambertsen, and R. Schmutzler, 2. Naturforsch., B:, 1995,50, 1583. M. Pabel, A. C. Willis, and S . B. Wild, Inorg. Chem.. 1996,35, 1244. M. Pabel, A. C. Willis, and S . B. Wild, Tetrahedron: Asymmetry, 1995,6,2369. Y. Ehleiter, G. Wolmershauser, H. Sitzmann, and R. Boese, 2.Anorg. Allg. Chem., 1996,622,923. J. R. Goerlich and R. Schmutzler, Phosphorus, Suvur, Silicon, Relat. Elem., 1995, 102,211. F. Knoch, S. Kummer, and U. Zenneck, Synthesis, 1996,265. A. Longeau, F. Langer, and P. Knochel, Tetrahedron Lett., 1996,37,2209. C. M. D. Komen and F. Bickelhaupt, Synth. Commun., 1996,26,1693. A. A. Tolmachev, S. P. Ivonin, and A. M. Pinchuk, Heteroat. Chem., 1995,6,407. A. A. Tolmachev, S. P. Ivonin, A. A. Chaikovskaya, and T. E. Terikovskaya, Zh. Obshch. Khim.,1995,65,2059 (Chem. Abstr., 1996,124,343 478). A. A. Tolmachev, A. A. Yurchenko, E. S. Kozlov, A. Merkulov, M. G. Semenova, and A. M. Pinchuk, Heteroat. Chem., 1995,6,419.

I : Phosphines and Phosphonium Salts

55

285. M. V. Sendyurev and B. I. Ionin, Zh. Obshch. Khim., 1995,65,1046 (Chem. Abstr., 1996,124,117450). 286. M. V. Sendyurev, S. A. Shilov, and B. I. Ionin, Zh. Obshch. Khim.,1995,65, 1048 (Chem. Abstr., 1996,124,146303). 287. V.Stenzel, J. Jeske, W-W. du Mont, and P. G. Jones, Inorg. Chem., 1995,34,5166. 288. R. Boukherroub, E. Garrigues, and G. Manuel, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995,105,101. 289. A. S. Balueva and G. N. Nikonov, Izv. Akad. Nauk, Ser. Khim., 1993,378 (Chem. Abstr., 1996,124,87134). 290. 1. G. Trostyanskaya, M. A. Kazankova, and I. P. Beletskaya, Zh. Org. Khim., 1995, 31,651 (Chem. Abstr., 1996,124,232601). 291. M. Yoshifuji, S.Ito, K.Toyota, and M. Yasunami, Heteroat. Chem., 1996,7,23. 292. G. Jochem, A. Schmidpeter, and H. Noth, 2. Naturforsch., B: Chem. Sci,, 1996,51, 267. 293. G. Bouhadir, R. W. Reed, R. Reau, and G. Bertrand, Heteroat. Chem., 1995, 6, 371. 294. H.H.Karsch, T. Rupprich, and M. Heckel, Chem. Ber., 1995,128,959. 295. V. A. Pinchuk, C. Muller, A. Fischer, H. Thonnesson, P. G. Jones, R. Schmutzler, L. N. Markovsky, Y. G. Shermolovich,and A. M. Pinchuk, Z . Anorg. Allg. Chem., 1995,621,2001. 296. 0 .I. Kolodiazhnyi and E. V. Grishkun, Tetrahedron: Asymmetry, 1996,7,967. 297. D.Prevote, C. Galliot, A-M. Caminade, and J-P. Majoral, Heteroat. Chem., 1995,6, 313. 298. R. I. Yurchenko, E. E. Lavrova, and A. G. Yurchenko, Zh. Obshch. Khim.,1995,65, 1445 (Chem. Abstr., 1996,124,343466). 299. J. W. Grissom and D. Huang, Angew. Chem., Int. Ed. Engl., 1995,34,2037. 300. D. W . Lee and J. G. Morse, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,106,211. 301. J. R.Durig and T.K. Gounev, J. Mol. Struct., 1995,350,19. 302. V . A. Naumov and V . Yu. Nesterov, Zh. Strukt. Khim.,1995,36,674. 303. F. Dallemer, J. Collin and H. B. Kagan, Applied Organometallic Chem., 1995,9, 431. 304. A.R. Katritzky, H. Wu, L. Xie, and J. Jiang, J. Heterocycl. Chem., 1995,32,595. 305. M.Lequan, R. M. Lequan, K. Chane-Ching, P. Bassoul, G. Bravic, Y.Barrans, and D. Chasseau, J. Muter. Chem., 1996,6,5. 306. U.Engelhardt, B. M. Rapko, E. N. Duesler, D. Frutos, R. T. Paine, and P. H. Smith, Polyhedron, 1995,14,2361. 307. K. Pietrusiewicz,W. Wisniewski, W. Wieczorek, and A. Brandi, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,101,253. 308. L. D. Quin and G. Keglevich, Magy. Kem. Foly., 1995,101,282(Chem. Abstr., 1995, 123,286 153). 309. S. Warren and P. Wyatt, Tetrahedron: Asymmetry, 1996,7,989. 310. K. Seo, M.Yamashita, T. Oshikawa, and J. Kobayashi, Carbohydr. Res., 1996,281, 307. 311. V. E.Baulin, A. F. Solotnov, and E. N. Tsvetkov, Zh. Obshch. Khim., 1995,65,387 (Chem. Abstr., 1995,123,286157). 312. J. R. Goerlich and R. Schmutzler, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 101,213. 313. N. A. Bondarenko, 0. K. Bozhko, and E. N. Tsvetkov, Izv. Akad. Nauk SSSR, Ser. Khim., l995,139(Chem.Abstr., 1995,123,198941). 314. S. V. Matveev, A. G. Matveeva, E. I. Matrosov, B. K. Shcherbakov, Yu. M. Polikarpov, and M. I. Kabachnik, Izv. Akad. Nauk, Ser. Khim., 1994, 2007 (Chem. Abstr., 1995,123,83482). 315. C. Darcel, C. Bruneau, and P. H. Dixneuf, Synthesis, 1996,711. 316. X. Huang, C.Zhang, and X . Lu, Synthesis, 1995,769. 317. C. L. Ma, X. Y.Lu, and Y. X. Ma, Chin. Chem. Lett..1995,6,747(Chem. Abstr., 1996,124,56093).

56 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334. 335. 336. 337. 338. 339. 340. 341. 342. 343. 344. 345. 346. 347. 348. 349. 350. 351. 352.

Organophosphorus Chemistry

N. J. Lawrence, J. Liddle, and D. A. Jackson, Tetrahedron Lett., 1995,36,8477. C. Dieleman, C. Loeber, D. Matt, A. De Cian, and J. Fischer, J. Chem. SOC.,Dalton Trans., 1995, 3097. J. F. Malone, D. J. Marrs, M. A. McKervey, P. O’Hagan, N. Thompson, A. Walker, F. Arnaud-Neu, 0. Mauprivez, M-J. Schwing-Weil, J. F. Dozol, H. Rouquette, and N. Simon, J. Chem. SOC.,Chem Commun.. 1995,2151. F. Arnaud-Neu, V. Bohmer, J-F. Dozol, C. Gruttner, R. A. Jakobi, D. Kraft, 0. Mauprivez, H. Rouquette, M-J. Schwing-Weill,N. Simon, and W. Vogt, J. Chem. SOC.,Perkin Trans. 2, 1996,1175. G. Gelbard, F. Breton, M. Benelmoudeni, M-Th. Charreyre, and D. Dong, Polym. Mater. Sci. Eng., 1994,71,731. T. N. Mitchell, and B. Godry, J. Organomet. Chem.. 1996,516, 133. K. Bieger, G. Heckmann, E. Fluck, F. Weller, K. Peters, and E. M. Peters, 2. Anorg. Allg. Chem., 1995,621, 1981. G. Heckmann and E. Fluck, Magn. Reson. Chem., 1995,33,553. H-J. Cristau, P. Mouchet, J-F. Dozol, and H. Rouquette, Heteroat. Chem., 1995, 6, 533. J. Clayden, A. B. McElroy, and S . Warren, J. Chem. SOC.,Perkin Trans. I , 1995, 1913. A. Nelson and S . Warren, Tetrahedron Letters, 1996,37, 1501. H . J. Mitchell and S . Warren, Tetrahedron Lett., 1996,37,2105. J. Clayden and S . Warren, Angew. Chem., In?. Ed. Engl., 1996,35,241. P. OBrien and S . Warren, Tetrahedron Lett., 1995,36, 8473. P. O’Brien and S . Warren, Tetrahedron Lett., 1996,37,4271. J-K. Erguden and E. Schaumann, Synthesis, 1996,707. F. Palacios, D. Aparicio, and J. M. de 10s Santos, Tetrahedron, 1996,52,4123. M. Boukraa, N. Ayed, A. Ben. Akacha, H. Zantour, and B. Baccar, Phosphorus, Sulfur, Silicon, Relat. Elem,, 1995, 105, 17. F. Palacios, D. Aparicio, J. M. de 10s Santos, and E. Rodriguez, Tetrahedron Lett., 1996,37,1289. D. Price and N. Simpkins, Tetrahedron Lett., 1995,36,6135. I. L. Odinets, 0. I. Artyushin, R. M. Kalyanova, M. Yu. Antipin, K. A. Lysenko, Yu. T. Struchkov, P. V. Petrovskii, T. A. Mastryukova, and M. I. Kabachnik, Zh. Obshch. Khim., 1994,64, 1957 (Chem. Abstr., 1995,123,169 708). V. Vassileva, S. Varbanov, and E. Tashev, 2.Naturforsch., B: Chem. Sci., 1995, SO, 1086. J. B. Hendrickson, T. J. Sommer, and M. Singer, Synthesis, 1995, 1496. A. N. Yarkevich, E. V. Smolina, 0. V. Novikova, and E. N. Tsvetkov, Zh. Obshch. Khim., 1995,65,616 (Chem. Abstr., 1996,124,8915). E. F. Birse, M. D. Ironside, and A. W. Murray, Tetrahedron Lett., 1995,36,6309. R-Y. Zhang and C-G. Zhao, Chem. Commun., 1996,511. R.Langner and G. Zundel, J. Phys. Chem., 1995,99,12 214. E. Pens and R. H. Crabtree, J. Chem. Soc., Chem. Commun.. 1995,2179. S . Shiratori, S. Yasuike, J. Kurita, and T. Tsuchiya, Chem. Pharm. Bull., 1994,42, 2441. A. Brandi, S.Cicchi, F. Gasparrini, F. Maggio, C. Villani, M. Koprowski and K. M. Pietrusiewicz,Tetrahedron: Asymmetry, 1995,6,2017. A. Blasko, C. A. Bunton, E. A. Toledo, P. M. Holland, and F. Nome, J. Chem. Soc., Perkin Trans.2, 1995,2367. S . Yasui, K. Shioji,A. Ohno, and M. Yoshihara, Heteroat. Chem., 1995,6,275. N . K. Gusarova, E. E. Kuznetsova, S. N. Arbuzova, S. I. Shaikhudinova, S. F. Malysheva, G. V. Kozlova, E. F. Zorina, and B. A. Trofimov, Khim.-Farm. Zh., 1994,28,37 (Chem. Abstr., 1996,124,87138). T.Kaukorat, I. Neda, and R. Schmutzler, 2. Naturforsch., B: Chem. Sci., 1995, 50, 1818. J. B. Lambert and Y .Zhao, J. Am. Chem. SOC.,1996,118,3156.

1: Phosphines and Phosphonium Salts

57

353. I. M. Aladzheva, 0. V. Bykhovskaya, D. I. Lobanov, K. A. Lyssenko, 0. V. Shishkin, M. Yu. Antipin, Yu. T. Struchkov, T. A. Mastryukova, and M. I. Kabachnik, Mendeleev Commun., 1996,48. 354. M. Wada, S.Hayase, M. Fujiwara, T. Kawaguchi, T. Iwasaki, A. Uo, and T. Erabi, Bull. Chem. SOC.Jpn., 1996,69,655. 355. M. W. Wieczorek, G. D. Bujacz, W. R. Majzner, P. P. Graczyk, and M. Mikolajczyk, Heteroat. Chem., 1995,6,377. 356. M.K.Tasz, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,103,137. 357. B. M. Butin and A. P. Logunov, Zh. Obshch. Khim., 1995,65,1432 (Chem. Abstr., 1996,124,343464). 358. Z . G. Fang, T. S. A. Hor, Y.S. Wen, L. K. Liu, and T. C. W. Mak, Polyhedron, 1995,14,2403. 359. R. J. Cross, L. J. Farrugia, P. D. Newman, R. D. Peacock, and D. Stirling, J. Chem. Res., (S), 1996,222. 360. F. Sarikahya, Y. Sarikahya, I. Topaloglu, and L. Yuceer, Chim. Acta Turc., 1995, 23,31 (Chem. Abstr., 1995,123,314086). 361. M. M. Wienk, R. A. J. Janssen, and E. W. Meijer, Synth. Met., 1995,71,1833. 362. Y. Dong, S. Yan, V. G. Young, and L. Que, Angew. Chem. Int. Ed. Engl., 1996,35, 618. 363. G. Pilloni, G.Valle,C. Corvaja, B. Longato, and B. Corain, Inorg. Chem., 1995,34, 5910. 364. M. C. Gimeno, P. G. Jones, A. Laguna, and C. Sarroca, J. Chem. SOC.,Dalton Trans., 1995,3563. 365. L. Hansen, E.Alessio, M. Iwamoto, P. A. Marzilli, and L. G. Marzilli, Inorg. Chim. Acta, 1995,240,413. 366. J. Weiss, T. Priermeier, and R. A. Fischer, Inorg. Chem., 1996,35,71. 367. J. Petrova, E. T. K. Haupt, S. Momchilova, and J. C. Tebby, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,102,231. 368. S . W. Ng,Main Group Met. Chem., 1995,18,603. 369. T. Kawakami, D. Tanizawa, I. Shibata, and A. Baba, Tetrahedron Lett.. 1995,36, 9357. 370. Q.T. H. Le, S. Umetani, T. Sasaki, T. Tomita, and M. Matsui, Bull. Chem. SOC. Jpn.. 1995,68,2867. 371. M. Valderrama, R. Contreras, M. Bascunan, S. Alegria, and D. Boys, Polyhedron, 1995,14,2239. 372. M. Valderrama and R. Contreras, Bol. SOC.Chil. Quim., 1995,40,1 1 1 (Chem. Abstr., 1995,123,112368). 373. D. Cauzzi, C. Graiff, M. Lanfranchi, G. Predieri, and A. Tiripicchio, J. Chem. SOC., Dalton Trans., 1995,2321. 374. D. Cauzzi, C. Graiff, M. Lanfranchi, G. Predieri, and A. Tiripicchio, J. Chem. SOC., Chem. Commun., 1995,2443. 375. M.B. Smith, A. M. 2. Slawin, and J. D. Woollins, Polyhedron, 1996,15,1579. 376. A. M. Z.Slawin, M. B. Smith, and J. D. Woollins, J. Chem. SOC..Dalton Trans., 1996,1283. 377. P. Bhattacharyya, A. M. Z. Slawin, D. J. Williams, and J. D. Woollins, J. Chem. SOC.,Dalton Trans., 1995,3189. 378. R.Cea-Olivares, J. Novosad, J. D. Woollins, A. M. Z. Slawin, V. Garcia-Montalvo, G. Espinosa-Perez, and P. Garcia y Garcia, Chem. Commun., 1996,519. 379. P. Bhattacharyya and J. D. Woollins, Polyhedron, 1995,14,3367. 380. S . Tamagaki, Mem. Fac. Eng., Osaka City Univ., 1994,35,179 (Chem. Abstr., 1995, 123,143 999). 381. T. S.Lobana and P. V. K. Bhatia, Ind. J. Chem., A:, 1996,35,158. 382. M. Mikolajczyk and P. P. Graczyk, J. Org. Chem., 1995,60,5190. 383. P. 0 .Graczyk and M. Mikolajczyk, J. Org. Chem., 1996,61,2995. 384. M. Mikolajczyk and P. P. Graczyk, Phosphorus, Suvur, Silicon, Relat. Elem., 1995, 103,111.

58

Organophosphorus Chemistry

385. F. Plendt, M. Cassagne, and H. J. Cristau, Tetrahedron, 1995,51,9551. 386. M. Wang and H.Zong, Polymersfor Advanced Technologies, 1996,7,35. 387. A. Chesney, M. R. Bryce, M. A. Chalton, A. S. Batsanov, J. A. K. Howard, J-M. Fabre, L.Binet, and S . Chakroune, J. Org. Chem., 1996,61,2877. 388. M. W. Ding, D. Q. Shi, W. J. Xiao, W. F. Huang, andT. J. Wu, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,102,59. 389. V. S. Brovarets, R. N. Vydzhak, T. K. Vinogradova, and B. S. Drach, Zh. Obshch. Khim., 1994,64,1048(Chem. Abstr., 1995,123,9538). 390. V. S . Brovarets, K. V. Zyuz, R. N. Vydzhak, T. K. Vinogradova, and B. S . Drach, Zh. Obshch. Khim.,l994,64,1642(Chem.Abstr., 1995,123,33178). 391. V. S . Brovarets, R. N. Vydzhak, A. N. Chernega, and B. S. Drach, Zh. Obshch. Khim., 1995,65,955(Chem. Abstr., 1996,124,176271). 392. N.N. Zemlyansky, I. V. Borisova, A. K. Shestakova, and Yu. A. Ustynyuk, Zzv. Akad Nauk, Ser. Khim., 1993,2143(Chem. Abstr., 1995,123,83513). 393. J. Vicente, A. Arcas, D. Bautista, A. Tiripicchio, and M. T. Camellini, New. J. Chem., 1996,u),345. 394. B. Assmann, K. Angermaier, M. Paul, J. Riede, and H. Schmidbaur, Chem. Ber., 1995,128,891. 395. W . Henderson and G. M. Olsen, Polyhedron, 1996,15,2105. 396. H. Maeda, T. Koide, T. Maki, and H. Ohmori, Chem. Pharm. Bull., 1995, 43, 1076. 397. K. F. Tebbe and T. Farida, 2. Naturforsch., B: Chem. Sci., 1995,50,1440. 398. K. F.Tebbe, M. El. Essawi, and S. Abd. El. Khalik, 2. Naturforsch., B: Chem. Sci.. 1995,50,1429. 399. K. F. Tebbe and T. Farida, 2. Naturforsch., B: Chem. Sci., 1995,50,1685. 400. M. Jansen and S. Strojek, 2. Naturforsch., B: Chem. Sci., 1995,50,1171. 401. M.Ghassemzadeh, K. Harms, and K. Dehnicke, Chem. Ber., 1996,129, 115; 1996, 129,259. 402. P.K. Bakshi, M. A. James, T. S. Cameron, and 0. Knop, Can. J. Chem., 1996,74, 559. 403. D.Albanese, D.Landini, and M. Penso, Tetrahedron Lett., 1995,36,8865. 404. W. Bubenheim and U. Muller, 2. Naturforsch., B: Chem. Sci., 1995,50,1135. 405. A. Muller, E. Diemann, E. Krickemeyer, H. Bogge, and C. Menke, Mona?. Chem., 1996,127,43. 406. H . Krautscheid, 2. Anorg. Allg. Chem., 1995,621,2049. 407. C. Nachtigal and W . Preetz, 2. Anorg. AlZg. Chem., 1966,622,509. 408. N.Korber, J. Daniels, and H. G. von Schnering, Angew. Chem.. Int. Ed. Engl., 1996, 35, 1107. 409. X-M. Zhang, A. J. Fry, and F. G. Bordwell, J. Org. Chem., 1996,61,4101. 410. I. Dance and M. Scudder, Chem. Eur. J., 1996,2,481. 41 1. F.Toda, K. Tanaka, and H. Sawada, J. Chem. Soc., Perkin Trans. I . 1995,3065. 412. D. W.Allen and P . Benke, J. Chem. Soc., Perkin Trans. I , 1995,2789. 41 3. H-J. Cristau and P. Mouchet, Phosphorus, Surfur. Silicon, Relat. Elem., 1995, 107, 135. 414. M. Sakamoto, I. Shimizu, and A. Yamamoto, Chem. Lett., 1995,1101. 415. Y. 0. Elkhoshnieh, Y.A. Ibrahim, and W. M. Abdou, Phosphorus, Sulfur,Silicon, Relat. Elem.,1995,101,67. 416. K. Miyashita, K.Kondoh, K. Tsuchiya, H. Miyabe, andT. Imanishi, J. Chem. SOC., Perkin Trans. I , 1996,1261. 417. D. Seyferth and T. C. Masterman, Macromolecules, 1995,28,3055. 418. K. Okuma, K. Ikari, M. Ono, Y.Sato, S. Kuge, H. Ohta, andT. Machiguchi, Bull. Chem. Soc.. Jpn., 1995,68,2313. 419. Yu. G. Gololobov, G. D. Kolomnikova, and T.0. Krylova, Izv. Akad. Nauk, Ser. Khim., l995,186(Chem.Abstr., 1995,123,198944). 420. 0.B. Smolii, D. B. Shakhnin, and B. S. Drach, Zh. Obshch. Khim., 1995,65,1225 (Chem. Abstr., 1996,124,146053).

1: Phosphines and Phosphonium Salts

421. 422. 423. 424. 425. 426. 427. 428. 429. 430. 431. 432. 433. 434. 435. 436. 437. 438. 439. 440. 441. 442. 443.

444. 445. 446. 447. 448. 449. 450. 451. 452. 453. 454. 455. 456. 457.

59

0. B. Smolii, E. S. Rebets, D. B. Shakhnin, and B. S . Drach, Zh. Obshch. Khim., 1995,65,700 (Chem. Abstr., 1996,124,8916). H. J. Bestmann, H. P. Oechsner, L. Kisielowski, C. Egerer-Siebe, and F. Hampel, Angew. Chem., Int. Ed. Engl., 1995,34,2017. G. Jochem, A. Schmidpeter, and H. Noth, Chem. Eur. J., 1996,2,221. H. Firouazabadi and M. Adibi, Synth. Commun., 1996, 26, 2429. A. Bohsako, C. Asakura, and T. Shioiri, Synlett., 1995, 1033. P. Kubisa and T. Biedron, React. Fmct. Polym., 1995, 27, 237 (Chem. Abstr., 1996, 124,145331). R. Li, R. L.Smith, and H. I. Kenttamaa, J. Am. Chem. Soc., 1996,118,5056. J. M. Miller and J. Ni, J. Mass Spectrom., 1996,31, 16. C . Imrie, T. A. Modro, P. H. Van Rooyen, C. C. P. Wagener, K. Wallace, H. R. Hudson, M. McPartlin, J. B. Nasirun, and L. Powroznyk, J. Phys. Org. Chem., 1995,8,41. G. Martin, Revs. Heteroat. Chem., 1995,13,25. D-L. An, K. Toyota, M. Yasunami, and M. Yoshifuji, Heteroat. Chem., 1995,6,33. D. L.An, K. Toyota, M. Yasunami, and M. Yoshifuji, J. Organomet. Chem., 1996, 508,7. M. Gouygou, M. Veith, C. Couret, J. Escudie, V. Huch, and M. Koenig, J. Organomet. Chem., 1996,514,37. R. Pietschnig and E. Niecke, Orgunometallics, 1996,15,891. V. D. Romanenko, V. L.Rudzevich, E. B. Rusanov, A. N. Chernega, A. Senio, J-M. Sotiropoulos, G. FVister-Guillouzo, and M. Sanchez, J. Chem. Soc., Chem. Commun., 1995,1383. H. Binder, B. Riegel, G. Heckmann, M. Moscherosch, W. Kaim, H-G. von Schnering, W. H h l e , H-J. Flad, and A. Savin, Inorg. Chem., 1996,35,2119.. K. B. Dillon, V. C. Gibson, and L. J. Sequeira, J. Chem. Soc.. Chem. Commun., 1995,2429. L. Weber, E. Dobbert, S. Buchwald, H. G. Stammler, and B. Neumann, 2.Anorg. Allg. Chern, 1995,621, 1407. A. Jouaiti, M. Geoffroy, and G. Bernardinelli, Chem. Commun.,1996,437. S . Schardt and K. Hafner, Tetrahedron Lett., 1996,37,3829. G. Miirkl, R. Hennig, H. Noth, and M. Schmidt, Tetrahedron Lett., 1995,36,6429. G. Miirkl and R. Hennig, Tetrahedron Lett., 1995,36,6655. K. Toyota, K. Tashiro, T. Abe, and M. Yoshifuji, Heteroat. Chem., 1994,5,549. S.Ito, K. Toyota, and M. Yoshifuji, Chemistry Letters, 1995,747. J. R. Goerlich and R. Schmutzler, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 101,245. A. B. Kostitsyn, H. Ruzek, H.Heydt, M.Regitz, and 0. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 1994,684 (Chem. Abstr., 1995,123,144 021). K. Paasch, M. Nieger, and E. Niecke, Angew. Chem., Int. Ed. Engl., 1995,34,2369. A. Bjarnason and I. Arnason, Inorg. Chem., 1996,35,3455. H-P. Schrodel, G. Jochem, A. Schmidpeter, and H. Noth, Angew. Chem., Int. Ed. Engl., 1995,34,1853. U. Salzner and S. M. Bachrach, J. Org. Chem., 1995,60,7101. W. W. Schoeller and U. Tubbesing, Chem. Ber., 1996,129,419. D. C . Mulhearn and S.M. Bachrach, J. Org. Chem., 1995,60,7110. M. T. Nguyen, A. Van Keer, K. Pierloot, and L. G. Vanquickenborne,J. Am. Chem. Soc., 1995,117,7535. T. W. Mackewitz and M. Regitz, Liebigs Ann., 1996,327. V . Thelen, D. Schmidt, M. Nieger, E. Niecke, and W. W. Schoeller, Angew. Chem., Int. Ed Engl., 1996,35,3 13. V. I. Vovnova, A. N. Gulenko, V. V. Pen’kovskii, and V. D. Romanenko, Ukr. Khim. Zh. (Russ. Ed.), 1994,60,656 (Chem. Abstr., 1996,124,87174). M-A. David, D. S. Glueck, G. P. A. Yap, and A. L.Rheingold, Organometallics, 1995,14,4040.

60 458. 459. 460. 461. 462. 463. 464. 465. 466. 467. 468. 469. 470. 471. 472.

Organophosphorus Chemistry

J. B. Alexander, D. S. Glueck, G. P. A. Yap, and A. L. Rheingold, Orgunometallics, 1995,14,3603. M. van der SlUis, J. B. M. Wit, and F. Bickelhaupt, Orgunometallics,1996,15, 174. R. B. Bedford, A. F. Hill, and C. Jones, Angew. Chem., Znt. Ed. Engl., 1996,35,547. H. Trauner, E. de la Cuesta, A. Marinetti, and F. Mathey, Bull. SOC.Chim. Fr., 1995,132,384. L. Weber, 0. Sommer, H. G. Stammler, B. Neumann, and U. Kolle, Chem. Ber., 1995,128,665. N. H. T. Huy, L. Ricard, and F. Mathey, Organometallics, 1995,14,4048. L. Weber, 0. Kaminski, B. Quasdorff', A. Ruehlicke, H-G. Stammler, and B. Neumann, Orgunometallics,1996,1S, 123. L. Weber, 0. Sommer, H-G. Stammler, B. Neumann, G. Becker, and H. Kraft, Chem. Ber.. 1996,129,219. L. Weber, Angew. Chem., In?. Ed. Engl.. 1996,35,271. M. Driess, Coord Chem. Rev., 1995,145,l. M. Driess, H. Pritzkow, S. Rell, and U. Winkler, 1845.0rgunometullics, 1996, 15, M. Driess and H. Pritzkow, 2.Anorg. Allg. Chem., 1996,622,858. A. B. Rozhenko, M. I. Povolotskii, and V. V. Polovinko, Mugn. Reson. Chem., 1996, 34,269. N. Potschke, D. Barion, M. Nieger, and E. Niecke, Tetrahedron, 1995,51,8993. A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova, and I. P. Beletskaya, Zh. Org. Khim.,1995,31,495 (Chem. Abstr., 1996,124,261 167). A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova, and I. P. Beletskaya,Zh. Org. Khim.,1995,31,404 (Chem. Abstr., 1996,124, 146 272). A. H. Cowley, F. P. Gabbai, S. Corbelin, and A. Decken, Znorg. Chem., 1995, 34, 5931. L. D. Quin and A. S.Ionkin, J. Org. Chem., 1995,60,5186. G. Jochem, K. Karaghiosoff, S. Plank, S. Dick, and A. Schmidpeter, Chem. Ber., 1995,128,1207. G. Jochem, A. Schmidpeter, F. Kulzer, and S . Dick, Chem. Ber.. 1995,128,1015. A. Schmidpeter, S. Plank, and K. Polborn, 2.Nururforsch.. B: Chem. Sci., 1995,50, 1543. J. F. Nixon, Chem. SOC.Reviews, 1995,24,319. M. Regitz, A. Hoffmann, and U. Bergstraesser, in Mod. Acetylene Chem., Ed. P. J. Stang, VCH: Weinheim, 1995, pp 173-201. L. Weber, Chem. Ber., 1996,129,367. M. D. Francis, D. E. Hibbs, M. B. Hursthouse, C . Jones, and K. M. A. Malik, Chem. Commun., 1996,631. B. S . Jursic, THEOCHEM, 1995,342, 121. H. Heydt, U. Bergstrasser, R. Fassler, E. Fuchs, N. Kamel, T. Mackewitz, G. Michels, W. Rosch, M. Regitz, P. Mazerolles, C. Laurent, and A. Faucher, Bull. Soc. Chim. Fr.. 1995,132,652. T. W. Mackewitz and M. Regitz, Synthesis, 1996,100. M. Julino, U. Bergstrasser,and M.Regitz, J. Org. Chem., 1995,450,5884. M. Julino, U. Bergstrisser, and M. Regitz, Synthesis, 1996,87. M. Julino, M. Slang, U. Bergstrasser, F. Mercier, F. Mathey, and M. Regitz, Chem. Ber., 1995,128,991. T.W. Mackewitz, U. Bergstraser, S. Leininger, and M. Regitz, Heteroat. Chem.. 1995,6,617. B. Breit and M. Regitz, Chem. Ber., 1996,129,489. K. K. Laali,.B. Geissler, M. Regitz, and J. J. Houser, J. Org. Chem., 1995,450,6362. J. A. C. Clyburne and M. J. Schriver,Znorg. Chem., 1996,35,3062. R. Streubel, L. Ernst, J. Jeske, and P. G. Jones, J. Chem. Soc.. Chem. Commun., 1995,2113. H . Pucknat, J. Grobe, D. Le Van, B. Broschk, M. Hegemann, B. Krebs, and M. Lage, Chem. Eur, J., 1996,2,208. I

473. 474. 475. 476. 477. 478. 479. 480. 481. 482. 483. 484. 485. 486. 487. 488. 489. 490. 491. 492. 493. 494.

I : Phosphines and Phosphonium Salts

495. 496. 497. 498. 499. 500. 501. 502. 503. 504. 505. 506. 507. 508. 509. 510. 511. 512. 513. 514. 515. 516. 517. 518. 519. 520. 521. 522. 523. 524. 525. 526. 527. 528. 529.

61

S. Parsons, J. Passmore, X.Sun, and M. Regitz, Can. J. Chem., 1995,73,1312. M. Scheer, K. Schuster, T. A. Budzichowski, M. H. Chisholm, and W. E. Streib, J. Chem. Soc., Chem. Commun., 1995, 1671. J. Foerstner, F. Olbrich, and H. Butenschon, Angew. Chem., Znt. E d Engl., 1996,35, 1234. J. Grobe, D. Lc Van, F. Immel, M. Hegemann, B. Krebs, and M. Lage, 2. Anorg. Allg. Chem., 1996,622,24. D. Pohl, J. Ellermann, M. Moll, F. A. Knoch, and W. Bauer, 2.Naturforsch., B: Chem. Sci., 1966,622,283. J . Grobe, D. Le Van, F. Immel, M. Hegemann, B. Krebs, and M. Laege, 2. Anorg. Allg. Chem.. 1996,622,24. P. Binger, G. Glaser, S. Albus, and C. Kruger, Chem. Ber., 1995,128, 1261. P. Binger, S. Leininger, J. Stannek, B. Gabor, R. Mynott, J. Bruckmann, and C. Kruger, Angew. Chem., In?. Ed Engl., 1995,34,2227. P. B. Hitchcock, C. Jones, and J. F. Nixon, J. Chem. SOC., Chem. Commun., 1995, 2167. P. Mathur, M. M. Hossain, P. B. Hitchcock, and J. F. Nixon, Organometallics, 1995, 14,3101. N. Carr, M. Green, M.F. Mahon, C. Jones, and J. F. Nixon, J. Chem. Soc., Chem. Commun., 1995,2191. R. Gleiter, S. J. Silverio, P. Binger, F. Sandmeyer, and G. Erker, Chem. Ber., 1995, 128,775. G. M. Jamison, R. S. Saunders, D. R. Wheeler, M. D. McClain, D. A. Loy, and J. W. Ziller, Organometallics, 1996,15, 16. L. V. Ermolaeva and A. 1. Konovalov, Zzv. Akad Nauk Ser. Khim., 1994, 172 (Chem. Abstr., 1995,123,33207). L. Weber, B. Torwiehe, G. Bassmann, H-G. Stammler, and B. Neumann, Organometallics, 1996, 15, 128. D. Gudat, A. W. Holderberg, S. Kotila, and M. Nieger, Chem. Ber., 1996,129,465. H. Nakazawa, Y.Yamaguchi, T. Mizuta, and K. Miyoshi, Organometallics, 1995, 14,4173. N. Burford, P. Losier, P. K. Bakshi, and T. S . Cameron, Chem. Commun., 1996,307. M. Veith, W. Kruhs, and V. Huch, Phosphorus. Suljiur, Silicon, Relat. Elem.. 1995, 105,217. R. W. Reed, Z. W. Xie, and C. A. Reed, Organometallics,1995,14,5002. H-U. Reisacher, E. N. Duesler, and R. T. Paine, Chem. Ber., 1996,129,279. B. K. Schmiedeskamp, J. G. Reising, W. Malisch, K. Hindahl, R. Schemm, and W.S . Sheldrick, Organometallics, 1995,14,4446. W . Malisch, U-A. Hirth, K. Griin, M. Schmeusser, 0. Fey, and U. Weis, Angew. Chem., Int. Ed Engl., 1995,34,2500. W. Malisch and H. Pfister, Organometallics, 1995,14,4443. W. Malisch, K. Gruen, U-A. Hirth, and M. Noltemeyer, J. Organomet. Chem., 1996, 513,31. D. Gudat, M. Schrott, and M. Nieger, J. Chem. SOC.,Chem. Commun., 1995,1541. W. W. Schoeller and U. Tubbesing, THEOCHEM, 1995,343,49. Y . Canac, A. Baceiredo, H. Gornitzka, D. Stalke, and G. Bertrand, Angew. Chem., Int. Ed Engl.., 1995,34,2677. M. C. Fermin and D. W. Stephan, J. Am. Chem. Soc.,1995,117,12645. N. H. T. Huy and F. Mathey, Synlett., 1995,353. B. Wang, C. H. Lake, and K. Lammertsma, J. Am. Chem. Soc., 1996,118,1690. T.L. Breen and D. W. Stephan, J. Am. Chem. Soc., 1996,118,4204. T. L. Breen and D. W .Stephan, J. Am. Chem. Soc., 1995,117,11914. A. Mahieu, A. Igau, and J-P.Majoral, Phosphorus, Suljiur, Silicon, Relat. Elem., 1995,104,235. B. Riegel, A. Pfitzner, G. Heckmann, H.Binder, and E. Fluck, 2. Anorg. AZZg. Chem., 1995,621,1365.

62

Organophosphorus Chemistry

530. K. Eichele, R. E. Wasylishen, J. F. Corrigan, N. J. Taylor, and A. J. Carty, J. Am. Chem. SOC.,1995,117,6961. 531. T.P. Hamilton, A. G. Willis, and S . D. Williams, Chem. Phys. Lett., 1995,246,59. 532. G . Keglevich, K.Ujszaszy, G. S. Quin, and L. D. Quin, Phosphorus, Surfur, Silicon, Relat. Elem., 1995,106,155. 533. L. D. Quin, P. Herrmann, and S . Jankowski, J. Org. Chem., 1996,61,3944. 534. M.J. P. Harger and B. T. Hurman, J. Chem. Soc., Chem. Commun., 1995,1701. 535. B. Kramer, E.Niecke, M. Nieger, and R. W. Reed, Chem. Commun., 1996,513. 536. K. Toyota, H. Takahashi, K. Shimura, and M. Yoshifuji, Bull. Chem. SOC.Jup., 1996,69,141. 537. E.Niecke, P. Becker, M. Nieger, D. Stalke, and W. W. Schoeller, Angew. Chem., Int. Ed. Engl., 1995,34,1849. 538. R. Armbrust, M. Sanchez, R. Reau, U. Bergstrasser, M. Regitz, and G. Bertrand, J. Am. Chem. Soc., 1995,117,10785. 539. B.Deschamps and F. Mathey, Synthesis, 1995,941. 540. A. Ostrowski, J. Jeske, P.G. Jones, and R. Streubel, J. Chem. SOC.,Chem. Commun., 1995,2507. 541. A. J. A r e , Y. Desanctis, R. Machado, M. V. Capparelli, J. Manzur, and A. J. Deeming, Organometallics,1995,14,3592. 542. Y . Canac, M.Soleilhavoup, L. Ricard, A. Baceiredo, and G. Bertrand, Organometallics, 1995,14,3614. 543. D. Fabbri, A. Dore, S. Gladiali, 0.De Lucchi, and G. Valle, Gazz. Chim. Itul., 1996, 126,ll. 544. L. Nyulaszi, J. Phys. Chem.. 1996,100,6194. 545. S . Holand, F. Gandolfo, L. Ricard, and F. Mathey, Bull. SOC.C h h . Fr., 1996,133, 33. 546. E. Deschamps, L. Ricard, and F. Mathey, J. Chem. Soc., Chem. Commun..1995, 1561. Siah, P-H.Leung, and K.F. Mok, J. Chem. SOC.,Chem. Commun., 1995,1747. 547. S-Y. 548. S . hlikvre, F.Mercier, and F. Mathey, J. Org. Chem.. 1996,61,3531. 549. P-H. Leung, S-K.Loh, K. F. Mok, A. J. P. White, and D. J. Williams, Chem. Commun., 1996,591. 550. W. L. Wilson, J. Fischer, R. E. Wasylishen, K. Eichele, V. J. Catalano, J. H. Frederick, and J. H. Nelson, Inorg. Chem., 1996,35,1486. 551. K. Eichele, R. E. Wasylishen, J. M. Kessler, L. Solujic, and J. H.Nelson, Inorg. Chem., 1996,35,3904. 552. V. Caliman, P.B. Hitchcock, and J. F. Nixon, J. Chem. SOC.,Chem. Commun., 1995, 1661. 553. S.M.Bachrach, V. Caliman, and J. F. Nixon, J. Chem. SOC..Chem. Commwz., 1995, 2395. 554. F. Paul, D. Carmichael, L. Ricard, and F. Mathey, Angew. Chem., Int. Ed Engl., 1996,35,1125. 555. F. G. N.Cloke, K. R. Flower, P. B. Hitchcock, and J. F. Nixon, J. Chem. Soc., Chem. Commun.. 1995,1659. 556. A. J. Ashe, S. Alahmad, S. Pilotek, D. B. Puranik, and C. Elschenbroich, Organometallics, 1995,14,2689. 557. L. Weber, 0.Sommer, H-G. Stammler, and B. Neumann, 2.Anorg. Allg. Chem., 1996,622,543. 558. P . B. Hitchcock, J. A. Johnson, and J. F. Nixon, Organometallics, 1995,14,4382. 559. R. Beugelmans and M . Chbani, Bull. SOC.Chim. Fr., 1995,132,306. 560. R. Beugelmansand M . Chbani, Bull. Soc. Chim. Fr., 1995,132,729. 561. S . V. Chapyshev, U.Bergstrasser, and M. Regitz,Izv. A M . Nauk, Ser. Khim.,1996, 252 (Chem. Abstr., 1996,124,317306). 562. P . de Dianous, S. Himdi-Kabbab, and J. Hamelin, Heteroat. Chem., 1995,6,403. 563. N. G . Khusainova, T.A. Zyablikova, Z. M. Farukshina, and R.A. Cherkasov, Zh. Obshch. Khim., 1995,65,761(Chem. Abstr., 1996,12429865).

I : Phosphines and Phosphoniwn Salts 564. 565. 566. 567. 568.

63

D. J. Berger, P. P. Gaspar, and J. F. Liebman, THEOCHEM, 1995,338,51. J. Lorentzon, M. P. Fuelscher, and B. 0. Roos, Theor. Chim. Acta, 1995,92,67. H. T. Teunissen, J. Hollebeek, P. J. Nieuwenhuizen, B. L. M. Van Baar, F. J. J. de Kanter, and F. Bickelhaupt, J. Urg. Chem., 1995,60,7439. K. Waschbusch, P. Le Floch, and F. Mathey, Bull. SOC.Chim.Fr., 1995,132,910. D. Cannichael, P.Le Floch, H. G. Trauner, and F. Mathey, Chem. Commun., 1996, 971.

569. 570. 571. 572. 573. 574. 575. 576. 577.

K. Waschbusch, P. Le Floch, and F. Mathey, Urganometallics, 1996,15, 1597. T. T. Teunissen and F. Bickelhaupt, Urganometallics, 1996, 15, 794. T. T. Teunissen and F. Bickelhaupt, Organometallics, 1996,15,802. F. Mathey and P. Le Floch, Chem. Ber., 1996,129,263. P. Le Floch, N. Maigrot, L. Ricard, C. Charrier, and F. Mathey, Znorg. Chem., 1995, 34,5070. M. Shiotsuka, T. Tanamachi, and Y. Matsuda, Chem. Lett., 1995,531. G . Keglevich, L. Toke, Z. Bocskei, D. Menyhard, and L. D. Quinn, Heteroat. Chem., 1995,6,593. E. Fluck, F. Rosche, G. Heckmann, and F. Weller, Heteroat. Chem., 1995,6,355. A. Foucaud and C. Bedel, Tetrahedron, 1995,51,9625.

2 Pentaco-ordinated and Hexaco-ordinated Compounds BY C. D. HALL

1

Introduction

The year was dominated by the superbly organised XIIIth International Conference on Phosphorus Chemistry (ICPC) in Jerusalem' (Aug. 1995) which included numerous contributions in the field of hypervalent phosphorus chemistry (vide infra). The period has also seen the publication of several important review articles in the area. Robert Holmes has provided an extremely informative comparison of the hypervalency, stereochemistry and reactivity of silicon and phosphorus including the application of the latter to enzyme systems.2 The coordination chemistry of hydrophosphoranes including the formation of complexes from bicyclic-, tricyclic- and tetracyclic hydrophosphoranes has also been the subject of an extensive review with literature coverage to 1995.3 Numerous metal complexes are mentioned including Rh, Ru, Pd, Co, Fe, Mo and W and the relevance to asymmetric catalysis is discussed. Neutral sixcoordinate compounds of phosphorus have also been reviewed again including mono-, di-, tri- and tetracyclic compound^.^ 2

Acyclic Phosphoranes

Relatively little has appeared on this topic throughout the year but by analogy with the chemistry of pentaphenykdntimony (eqn. 1) attempts were made to react pentaphenylphosphorus (1) with paraform (2) at 130 "C. The products were in fact triphenylphosphine (4), benzene and benzaldehyde, presumably via the desired tetraphenylbenzyloxyphosphorane(3).5 The reaction of (1) with pentan3-one ( 5 ) failed to give (6) - a known compound obtained via reaction of (7) with ethyl lithium6. The crystal structure of (6) is reported in reference 5. PhsSb

PhsP (1)

+ lln(CH20)"

-

130 "C

-

*

+ l/n(CH~0)~

[Ph4POCH2Ph]-

(2)

(3)

64

(1 1

PhdSbOCH2Ph

Ph3P (4)

+

PhH

+ PhMe

2: Pen taco-ordinatedand Hexaco-ordinated Compounds

65

Bestmann et al. have reported a facile route to novel diphosphaheterocycles which contain pentacoordinate and tetracoordinate phosphorus7. Reaction of (8) with sodium hexamethyldisilylamide (9) in benzene or pyridine gave (11) presumably via the anion (10). An X-ray crystal structure of (1 1, R = Me) showed a nearly ideal tbp with the new C-Pbond formed in the apical position and, as expected, the ylidic carbon in an equatorial position.

t

NaN(SiMe&

3

Monocyclic Phosphoranes

Mono- and bis-phosphonopyrimidinediones (14) have been synthesised in moderate to excellent yields from monocyclic phosphoranes (12) and isocyanates (13 ) and molecular modelling studies indicate that the deprotected bis-phosphonates may be effective inhibitors of bone resorption and mineralisation* which are symptoms of osteoporosis and Paget's disease. 0

R3\ N

R 2 R3NC0

(13) R3 = Ar. BOM. MOM or SiMe3

R = Me; R', R2 = H R = SiMe3; R', R2 = H R = Me, R' H, R2 = P(O)(OEt)2 R = SiMej R' = H, R2 = P(O)(OEt)Z '

P

-

KN33

Ry 70E02 0

66

Organophosphorus Chemistry

In a study designed to produce monoclonal antibodies which would catalyse the hydrolysis of phosphorus nerve agents, Moriarty et al. used a synthetic strategy involving a monocyclic phosphorane as hapten for the production of a monoclonal catalytic antibody based on the T.S.for phosphonate hydrolysis. These haptens (18 and 19), which are effective catalysts for the hydrolysis of Soman [Bu'MeCHOPMe(O)F], were generated from the reaction of (1 5 ) with the protected 3(S) aminoalcohols (16 and 17).9

OH

0

Me-P,

I OMe

Me-P,

I OMe

Methods for synthesising phosphoranes and spirophosphoranes containing a 1,3,23L5-oxazaphosphetidinering from N-methyl-N-trifluoroacetyl-phosphoramidites have been developed. For example the reaction of (20) with chlorine gave (22) via the intemiediate (21) and the spirophosphorane decomposed to (23) and (24) on heating to 120°C. Likewise reaction of (25) with (26) gave a mixture of two isomeric phosphoranes (28ab) via (27) in a ratio of 2:3 (28a:28b). The isomers were separable by fractional distillation and an X-ray crystallographic study of the more stable isomer (28a) was achieved.1°

2: Pentaco-ordinated and Hexaco-ordinated Compounh

0

(CF3CNMe)3P II +

I

Me

(25)

CF3CONCI

I

Me

(26)

F3C CF$OyxN' Me

67

CI Me O,I/N CF3 p\0xyCOCF3

the

Me

(284

Reaction of tetrachloro-o-benzoquinone(29) with the monocyclic trihalophosphoranes (30ab) in CHzClz gave the thermodynamically stable spirophosphoranes (3 lab) by substitution of the halogen at pentacoordinate phosphorus.'

4

Bicyclic and Tricyclic Phosphoranes

In a continuation of earlier studied2 on the synthesis of phosphorus-containing derivatives of sarcosine, Prishchenko et al. have shown that the reaction of the

68

Organophosphorus Chemistry

y<)

[

(32)

-[

0

+ MeOCH2N(Me)CH2C02Me

(33)

0

)

+ MeOH 010 CH2N(Me)CH2C02Me >P<

(34)

hydrospirophosphorane (32) with the aminoester (33) gives the spirophosphorane (34) by displacement of methanolI3. The isolated compound (88% yield) was identified by elemental analysis and multinuclear ('H, 13C and 31P) NMR. Further work in this area by Prishchenko has involved the reaction of (35) with the bis-butoxymethylamino esters (36a-c) to form (37a-c)14 and the reaction of the same hydrophosphorane with N,N-bis(methoxylmethy1)-piperazine (38) to form the bis-phosphorane(39)."

In a continuation of their momentous work on the structure of hypervalent molecules, Holmes et al. have reported the synthesis and structure (by X-ray crystallography) of a unique geometry in a pentacoordinate tetraoxyphosphorane (40) which has the same eight-membered ring as (41) in a diequatorial position. Thus (40) provides the first example of a phenyl group occupying an axial position of a tbp in preferencejo a more electronegative group.I6 The axial P-C bond length in (40) is 1.838(8)A, cpnsiderably shorter than the axial P-C lengths in PPhS {(1.889(7) and 1.9866(6)A}17which is ascribed to the presence of the more electronegativeligands in (40). The C-spiroxyphosphorane (42) is selectively deprotonated by LiHMDS at -78 "C to the lithiated u-anion (43) which on reaction with methyl iodide gives

2: Pentaco-ordinatedand Hexaco-ordinated Compoundr

69

(44)as a mixture of diastereomers in low (FA) diastereomeric excess. With a more acidic methylene group, however, (e.g., 45, EWG = C02Me) reaction with LiHMDS followed by treatment with benzaldehyde gave (46) and a 60/40 mixture of E/Z alkenes (47a,b). Hexacoordinate phosphorus compounds are implicated as intermediates in the reaction. l 8 0

0

4"

0

A" /TO

JU

'EWG

/70

(42) EWG = Ph or Naphthyl

T 0

(44)

(43)

0

9 i) LiHMDS

ii) PhCHO

0 (45) EWG = C02Me

0

b., I o'~-o-Li'

+

(474

0 (46)

An extensive report by Segall at the Jerusalem conference showed that bis-(ocarboxyary1)methylphosphine oxides (48) and bis-(o-amidoary1)methylphosphine oxides (49) cyclodehydrate in acidic media to give tbp spirodioxaphosphoranes (50) and spiroazoxaphosphoranes(53) respectively. The amide reaction proceeds through intermediates (51) and (52). The cyclic dioxaphosphoranes (but not the azoxaphosphoranes) were found to be stable at physiological pH and were

70

Organophosphorus Chemistry

converted to the corresponding phosphine oxides at pH >8.5. Thus the dioxaphosphoranes may be useful as transition state analogues and promoters of catalytic antibodies. 0

CO2- K+

0

COP- K+

-

(50)h3'P = 51.9 0

CONHMe

CONHMe

MeHN CONHMe

CONHMe

The complexation of Li+, Na+ and K+by seven macrocycles (54-60) and three podand ligands (61-63) all containing bicyclic phosphorane units has been investigated by 13C NMR. Both 1:l and 2:l (1igand:cation) complexes were observed in relative amounts depending on the cation and the ligand with the highest stability constants associated with oxygen and nitrogen heteroatoms, rather than sulfur. Selectivity for the cations was not pronounced except in the case of (59) which discriminated between Na+ and Li+ or K+and Li+ by factors of ca. lo0 and lo00respectively.20 Intramolecular cyslisation of the phosphine oxide (64)with the Mitsunobu reagent gave the 1,2,h5-azaphosphetidine (65) which was characterised by

2: Pentaco-ordinated and Hexaco-ordinated Compounh

(54)X=O

71

Y=O

(55)X = NMe Y = NMe (56)X=S

(57)X=O Y = S (58)X = 0 Y = NMe

Y=S

(59)

P

Me0

multinuclear ('H,31Pand "F) NMR and X-ray crystallography.21apbThe latter reveals a distorted tbp with apical nitrogen and oxygen atoms and hence (65) is the first example of a pentacoordinate 1,2-azaphosphetidine. The fourmembered ring is almost planar and the nitrogen atom is almost trigonalplanar with the plane of the attached benzene ring in the plane of the fourmembered ring. When (65a) with 631P= -29.9 was dissolved in d8-toluene a further 31Psignal was observed at 6 = -50.9 which was ascribed to the pseudorotomer (65b) with the nitrogen in an equatorial position. Heating (65)

72

Organophosphorus Chemistry

at 200°C for 5 days in a sealed tube gave a quantitative yield of the corresponding olefin (66) and the aminophosphorane (67) thus showing that (65) resembles a Wittig intermediate.

- H20 ,

Ph

In a communication devoted largely to tricoordinate and tetracoordinate benzodiazaphosphorinones, Schmutzler et al. describe the reaction of (68) with hexafluoroacetone to form the bicyclic phosphorane (69) which was characterised by multinuclear NMR and mass spectrometry.22Similarly, the reaction of (70a or 70b) with tetrachloro-o-benzoquinonegave (71a) or (71b) respectively but (72) with the same reagent gave the tetracoordinate structure (73). The reaction of

CI

(70ab)a; X = NMe b;X=O

(71ab)

73

2: Pentaco-ordinated and Hexaco-ordinated Compoundr

cl* CI

CI

(73)

(72)

(70a) with hexafluoroacetone also gave an unusual product in the form of the tricoordinate phosphordiamidite (74).23 Further aspects of the oxidative addition of hexafluoroacetone, perfluorinated diketones and tetrachloro-o-benzoquinoneto benzoxaza- and diazaphosphorinones were reported in Jerusalem24with some of the products (e.g. 76) from (75) being tricyclic pentacoordinate structure^.^^

(75)

In another report from the conference, Shevchenko described some unusual chemistry based on the oxidative addition of tetrachloro-o-benzequinoneto the chlorophosphonamidite (77). The initial adduct (78) rearranges spontaneously to (79) which reacts with diethylamine in successive reactions to form (80) and then (81). Compound (81) adds isocyanates to form a mixture of the hexacoordinate diastereomers (82a) and (82b) and (82a) was characterised by X-ray crystallography. On reaction with aryl azides (81) gives the mitterionic product (83)

74

Organophosphorus Chemistry 0 MeNKNMe I 1

cl'p-p'cI (77)

CI*, cl

CI

-

0

y'

(78)

c'

')-a

CI'

]

Cl

(79)

0

0

and reaction with hexafluoroacetone generates the ylide (84) which according to the X-ray data exists predominantly in the zwitterionic form (84b) and hence displays a new form of coordination at p h o s p h o r ~ s .We ~ ~ await full details on this intriguing system. Meanwhile, on more fully documented ground, further discussion has appeared on the conformational equilibria of phosphoranes with 5-alkyl-substituted 1,3,2dioxaphosphorinane rings attached diequatorially to five-coordinated phosphorus.26 A series of five tetraoxyphosphoranes (85 - 89) were prepared and their conformational properties studied by 'H NMR. It was concluded that although the equilibrium between (A) and (B) is readily perturbed by substitution of But for R' or R2 instead of hydrogen or by

2: Pentaco-ordinatedand Hexaco-ordinated Compounds

75

substitution of Me or Ph for R' instead of hydrogen, there was no evidence for depopulation of chair conformations (A) or (B) in favour of boatltwist forms (C), (D) or (E). It was emphasised that the result contrasts sharply with the known preference of 1,3,2-dioxaphosphorinancrings attached in apical-equatorial positions to occupy boatltwist conformations and the ease of population of boatltwist forms by 1,3,2-dioxaphosphorinanescontaining three or fourcoordinate phosphorus. The results were rationalised in terms of severe repulsive interactions between the apical P-O4 bond and the bowsprit hydrogen at C5 in (C) and the fact that when the 6-membered ring is diequatorial the lone pair on equatorial oxygen cannot be 'positioned to back bond with phosphorus in any non-chair conformation.' The commercially available nonionic superbase (90) is a very useful promoter for the acylation of hindered and acid-sensitive alcohols. In general, acylation using (90) is accelerated in acetonitrile whereas benzoylation occurs faster in a non-polar solvent, e.g. benzene. Strictly speaking this is not pentacoordinate phosphorus chemistry but the intermediate for the reactions (91a and 91b) is trigonal bipyramidal in configuration and acylates the substrate alcohol with the formation of (92ab) which can be deprotonated to regenerate It is of interest to note that molecules analogous to (90) have been synthesised and their structures established with Ti, Zr and Hf as the central azatrane atom.28

76

Organophosphorus Chemistry F3cbCF3

I

HB

A

B

I1 (85)R’ = R2 Me I

(86) R’ (87) R’ (88) R’ (89) R’

= Hx, R2 = But = Me, R2 = HY = Ph, R2 = Hy = Bu‘, R2 = Hy

C

C (R’ = Bu‘)

But

F 3 d ‘CF3 D

(90) R = Me

5

F3C CF3

E

(91) a; Z = PhC(O), R = Ph b; Z = MeC(O), R = Me

(92ab)

Hexaco-ordinated Phosphorus Compoands

The silylated derivatives of a number of Schiff bases react with halogenophosphoranes (e.g. PCls) or trifiuorornethylhalogenophosphoranes(CF3,PX5-, where X=Cl, n=1-3 and X=F, n=1,2) to give high yields of neutral, hexacoordinate phosphorus(V) compounds via elimination of two equivalents of Me3SiCl or Me3SiF. For example, phosphorus pentachloride reacts with (93) to give (94) which was characterised by NMR and X-ray crystallography. In all the cases

2: Pentaco-srdinated and Hexaco-ordinated Compoundr

+

77

PC15

d O S i M . 3 (94)

(93)

(97) a; R = Me b; R = Et

OEPH2

\ DBU

OH

(98)a; R = Et b; R = Ph

(99)a; R = Et b; R = Ph

Cl-

Organophosphorus Chemistry

78

studied, the ligands chelate in a meridional conformation in which the bicyclic five- and six-membered rings are formed from two phenolic P-0bonds and one P-N bond. The silylated form of the thiobisphenol (95) also reacts with pentavalent halides to form a six-coordinate complex but each compound possesses a facial structure (96) in which two phenoxy substituents form planar chelates centred on the bridging sulfur and intersecting the P-S Finally, the synthesis of a series of phosphorus(V) octaethylporphyrins containing o-P-C bonds has been reported.30 The synthetic routes from dihydrooctaethylporphyrin (OEPH2) to (97a,b) (98a,b) and (99a,b) are as shown. The compounds were characterised by ‘H and 13CNMR and in the case of (98a) and (99a)C104- suitable crystals for X-ray analysis were obtained by recrystallisation from dichloromethane and ethyl acetate respectively. The geometry about each phosphorus atom is a distorted octahedron, in which th? P - 0 bond length in (98a) at 1.487A is very short (cfPh,P(O), P = 0 at 1.483A) relative to the usual single bond length (1.635A) found in (99a)-C104.- The oxygen atom of the P-0 bond of (98a) however, is hydrogen-bonded to a water molecule incorporated in the c:ystal lattice with the closest hydrogen of the water molecule at a distance of 2.31A. It was also noted that the porphyrin core of (98a) was almost planar whereas that of (99a)-C104 was severely ruffled. Further news of these unusual molecules is awaited.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13.

14.

Report of the XIIIth International Conference on Phosphorus Chemistry, Jerusalem, 1995:Phosphonrs, Surfur and Silicon, 1996,109-111. R.R.Holmes, Chem. Rev., 1996,96,927. K. M.Gavrilov and I. S . Mikhel, Russ. Chem. Revs, 1996,65(3), 225. C. Y. Wong, D. K. Kennepohl and R.G. Cavell, Chem. Rev., 1996,96,1917. V. V. Zhidkov, V. V. Sharutin, V. K. Bel’skii and S . Magomedova, J. Gen. Chem., Int.ed. Eng., 1995,65(2,pt l), 214. V. V. Sharutin, V. T. Bychkov, R. I. Bochkova and E. A. Kuz’min, Zh. Obsch. Khim., 1986,s(2), 325. H.J. Bestmann, H. P. Oechsner, L. Kisielowski, C. Egerer-Sieber and F. Hampel, Angew. Chem. Int.ed. Eng., 1995,M(18),2017. C. K. McClure. R. C. Hausel, K. B. Hansen, C. W. Grote and K.-Y. Jung, Phosphorus, Surfur and Silicon, 1996,111,163. R. M. Moriarty, K. Liu, S. M. Tuladkar. L. Guo, C. Condeiu, A. Tao, W. Xu, D. Lenz and A. Brimfield, Phosphorus, Surfur and Silicon, 1996,109-110,237. A.D.Sinitsa, L. I. Nesterova, D. M. Malenko, V. V. Pirozhenko, E.B. Rusanov and A. N. Chernega, Rus. J. Gen. Chem.,1nt.ed. Eng., 1995,65,(2pt. l), 198. I. V. Konovalova, V. F. Mironov and M. G. Khanipova, Russ. J. Gen. Chem., Int. ed. Engl.1995,65, (2,pt. 2), 289. a) V.P. Kukhar’ and V. A. Solondenko, Usp. Khim., 1987,56(No.9), 1504. b) A. A. Prishchenko, M. V. Livantsov, K.-L. Lorents, M, Yu. Papsuev, E. V. Grigor’ev and Yu N. Luzikov, Zh. Obsch. Khim., 1994,64,(No.8), 1302. A. A. Prishchenko, 0. P. Novikova, M. V. Livantsov and E. V. Grigor’ev, Rus. J. Gen. Chem.,Int.ed. Eng., 1995,65(10pt. 2), 1604. A. A. Prishchenko, M. V. Livantsov, 0. P. Novikova, L. I. Livantsova and Yu.N. Luzikov, Russ. J. Gen. Chem., Int. Ed. Engl., 1995,65,(No. 10,pt. 2) 1606.

2: Pentaco-ordinated and Hexaco-ordinated Compounh 15. 16. 17. 18. 19. 20. 21.

22. 23. 24. 25. 26. 27. 28. 29.

79

A. A. Prishchenko, M. V. Livantsov, D. N. Kustrya and E. V. Grigor’ev, Russ. J. Gen. Chem., Znt. Ed Engl., 1995,65, (No. 10, pt. 2) 1610. T. V. Timosheva, T. K. Prakasha, A. Chandrasekaran, R. 0.Day and R. R. Holmes, Inorg. Chem., 1995,34,4525. P. J . Wheatley, J. Chem. Soc., 1964,2206. S. Barkallah, M. L. Bojin and S. A. Evans jn., Phosphorus, Suyur and Silicon, 1996, 111, 156. 0. Mir, M. Fridkin and Y.Segall, Phosphorus, Surfur and Silicon, 1996, 109-110, 241. D. Houalla and L. Moureau, Phosphorus, Surfur and Silicon, 1996,114,51. a) T . Kawashima, T. Soda and R. Okazaki, Angew Chem. Int. Ed. Engl., 1996, 35 (10) 1096. (b)T. Kawashima, T. Soda, K. Kato and R.Okazaki, Phosphoncs, Surfur and Silicon, 1996,109-110,489. C. Melnicky, I. Neda, and R. Schmutzler, Phosphorus, Surfur and Silicon, 1995,106, 65.

A. Vollbrecht, I. Neda, A. Fischer, P.G. Jones, and R. Schmutzler, Phosphorus, Surfur and Silicon, 1995,107,69. I. Neda, C. Melnicky, A. Vollbrecht, A. Fischer, P.G. Jones, A. Martens-von Salzen R. Schmutzler, U. Niemeyer B. Kutscher, and J. Engel, Phosphorus, Surfur and Silicon, 1996,109-110,629. I.V. Shevchenko, Phosphorus, Sulfur and Silicon, 1996,109-110,493. Y . Huang and W.G. Bentrude, J. Amer. Chem. Soc., 1995,117,12390. R.A.D’Sa, and J.G. Verkade, J. Org. Chem., 1996,61,2963. Z. Duan, A.A.Naiini, J.-H. Lee, and J.G.Verkade, Inorg. Chem., 1995,34, 5477. a) C.W. Wong, R.McDonald, and R.G.Cavel1, Inorg. Chem., 1996,35,325. b) R.G. Cavell, C.W. Wong, and R. McDonald, Phosphorus, Su@r and Silicon, 1996,111, 151.

30.

K. Yamamoto, R. Nadano, M. Itagaki, and K. Akiba, J. Amer. Chem. SOC.,1995, 117,8287.

3 Tervalent Phosphorus Acid Derivatives BY 0.DAHL

1

Introduction

The proceedings of the 13th International Conference on Phosphorus Chemistry, Jerusalem 1995, have appeared. The reports therein on tervalent phosphorus acid derivatives will not be covered here. The final volume of the chemistry of organophosphorus compounds in the Patai series, the chemistry of functional groups, contains a chapter on the preparation and properties of tervalent phosphorus acid derivatives.2 A new twelve volume work, Comprehensive Heterocyclic Chemistry 11, contains several chapters on phosphorus-containing heterocycles, many of which are tervalent phosphorus acid derivative^.^

2

Nucleophilic Reactions

2.1 Attack on Saturated Carbon. - A large number of phosphinic acid analogues of GABA have been prepared from the phosphinites (1) and protected aminoalkyloxiranes, e.g. (2).4*5 The diphenyl phosphonate analogue of tryptophan has been prepared by a route beginning with the Arbuzov reaction of diphenyl methyl phosphite with N-bromomethylphthalimide.6Bis(trimethylsily1) phosphonite (3), prepared in situ, gave with 1,n-dibromoalkanes in refluxing mesitylene moderate to good yields of cyclic phosphinic acids (4) in a one-pot rea~tion.~ Heating triphenyl phosphite and hydroxymethylferrocene( 5 ) without a solvent gave a 50% yield of diphenyl ferrocenylmethylphosphonate(6).’

OSiMes R-P ‘OEt

0 (1) R = Me, CHF2, CH(OEt)2, Bu, CH*Cy, or CH2Ph

0

(2)

2.2 Attack on Unsaturated Carbon. - A new method to obtain a-amino phosphonic acids (7) in high enantiomeric excess involves the selective addition of trimethyl phosphite to chiral oxazolidines (8).9 The reaction probably occurs by 80

3: Tervalent Phosphorus Acid Derivatives

OSiMe3 H-P,

f+

OSiMe3

Br

(CH2)

81

-

Lngr

r

0 &-OSiMe3

(CH2) LnBr

+

MesSi6r

I

(4) n = 3-7 3675%

attack of trimethyl phosphite on the immonium group of (9) generated by the Lewis acid catalyst. Racemic a-amino phosphinic acids (10) have been prepared on a solid support by addition of bis(trimethylsily1) phosphonite (3) to a supportbound imine (1 1). lo

R = Me, Et, Pr, (CH2)3COOMe,or CH2Ph 77-97Y0 e.e.

82

Organophosphorus Chemistry

PhP(OSiMe3)2

+

@COOR

--

0 Ph-P-

II

I OH

COOR

A full paper has appeared on the preparation of P-chiral fullerenephosphinites reported last year. A series of functionalised alkylphenylphosphinic acids has been synthesised by addition of in situ prepared bis(trimethylsily1) phenylphosphonite (1 2) to a range of electrophiles, e.g. (13). l2 Stereoselective syntheses of the four diastereomers of phosphothreonine have been described which are based on the stereoselective addition of diethyl trimethylsilyl phosphite (14) to protected lactaldehyde (1 5 ) or its imine. A similar procedure gave access to phosphomycin (16) via addition of (17) to the protected lactaldehyde (lS).I4

'

Osipri3 (R0)2POSiMe3

-- t-/

-

Me P(O)(OH)2

P O ,(O ,().C )H2Ph 2)

0

OSiMe3 (14) R = Et (17) R=CH2Ph

(15)

Some 1,2-dihydroisoquinoline-1-ylphosphonates, e.g. (1 8), have been prepared from trialkyl phosphites, isoquinoline, and a sulfonyl chloride. Quinoline gave -similarly the corresponding 1,2-dihydroquinoline-2-ylphosphonates. The superbase (19) has been shown to be a very effective catalyst for the acylation of hindered and/or acid-sensitive alcohols;16with benzoic anhydride a P-acylated intermediate (20) was inferred from NMR data. +

(Me0)3P

+

MeS02CI

CH2C12 r't.

q N - S 0 2 M e

2.3 Attack on Nitrogen, Chalcogen or Halogen. - Esterifications of racemic alcohols with acids have been realised with moderate enantiospecificity when

3: Tervalent Phosphorus Acid Derivatives

83

triphenylphosphine was replaced with the chiral phosphoramidite (2 1) under Mitsunobu ~0nditions.l~ Organic azides and P406 gave the first selective cagesubstituted product (22), the structure of which was confirmed by X-ray analysis. 0

+

Several new sulfur transfer reagents for the oxidation of oligonucleoside phosphites to phosphorothioates have been proposed this year. These include the disulfonyldisulfides(23), l9 and the two cyclic disulfides (24) and (25).20

0 II

9

0 II

0 II

R-S-S-S-S-R

(23) R = Prior X

e

r v 0

(24)

-4

-+ (Me2N)3P-I

I-

4fNH 0

(25)

(26)

, X = H,Me, CI, or Me0

Tris(dimethy1amino)phosphine with iodine in diethyl ether gave a solid which according to solid-state 31PNMR had the ionic structure (26) in contrast to most other phosphine-iodine addition compounds.21 N-Chlorodiisopropylamine reacted with aminophosphines, e.g. (27), to give products of chlorine attack, e.g. (28), instead of the usual attack at nitrogen.22

3

Electrophilic Reactions

3.1 Preparation. - A new method to prepare phosphonate or thiophosphonate esters and amides (29) involves the conversion of H-phosphinate esters (30) to tervalent chlorides (3 1) with dichlor~triphenylphosphine.~~ Dialkyl phosphites

Organophosphorus Chemistry

84

with triphenylphosphine and diisopropyl azodicarboxylate gave products, formulated as phosphoramidites (32)’ which with alcohols or phenol slowly gave p h o ~ p h i t e s .This ~ ~ ‘Mitsunobu phosphitylation’ also worked for monoalkyl phosphites (33) which gave dialkyl or alkyl aryl phosphonites (34) under similar conditions.

R1 = Me or Ph; R2,R3 = alkyl or aryl; X = 0, S, or NH; Y = 0 or S

(R10)2PH0

+

+

COOP+

Ph3P-N

I

1

-

NI

COOP+ I

R*OH

(R~O)~P--N I NH

(R’0)2POR2

I

COOP+

COOPr’

R’ = Me or Et

R2 = alkyl or aryl

(32)

Functionalised aminophosphines, e.g. (39, can be conveniently purified and stored as their air- and water-stable borane adducts (36); these with hydrogen chloride gave the chlorophosphine adducts (37) which were useful for the preparation of functionalised p h o ~ p h i n e sAn . ~ ~improved method to prepare Npyrrolylphosphines (38) and (39) has appeared.26 The related N-indolylphosphines (40) have been similarly prepared.27Two papers describe the preparation of the tervalent phosphorus hydrazides (41)28and (42)29 for use as chelating ligands.

R2Zn

+

C12P-NEt2

(35) R

BHs

R2P-NEt2

= MeCOO(CH2),,

BH3

t

R2P-NEt2

(36)

HCI

BH3

f

R2P-CI

(37)

3: Tervalent Phosphorus Acid Derivatives

85

Me

I (Me2PhN-N-PMe2

(40) n = 1-3

(41)

Me Me I I (R0)2P--N--N--P(OR)2 (42) R = alkyl or aryl

Calixarene phosphorus derivatives continue to be studied for their intriguing properties. New tervalent examples are the calix[4]arene diphosphonite (43),30the calix[6]arene diphosphite (44),31 and a tetra-phosphoramidite of a calix[4]resorcin01arene.~~

t (43)

The bicyclic phosphite (45), derived from TRIS, has been prepared and ~haracterised.~~ Several macrocyclic tervalent phosphorus acid derivatives, including (46)” and (47),35were obtained by known methods. Bis-derivatives of catechol, e.g. (48),36hydroquinone, e.g. (49),37 and p-phenylenediamine, e.g. (50),38have been prepared for the first time. Mercaptoaceticacid esters with phosphorus trichloride gave the thiophosphorodichloridites (51) which on heating cyclised to 1,3,2-0xathiaphospholanes (52);39 with traces of oxygen the more nucleophilic analogues, e.g. (53), rearranged at room temperature to the thiophosphonate derivatives, e.g. (54). The first ferrocenediyldiphosphonite (55) has been prepared by two routes, from the ferrocenediylbis(dich1orophosphine) and from the ferrocenedilithium compound.40

86

Organophosphorus Chemistry

p O ,nN "j '0

\/"Me (46) X = OorNH

,& o \ PhP,

O

V

d

P

P

h

(49) X = Ph or NEt2

PC13

+

HSCH2COOR

(50)

- PTO

-

h

Cl2P-SCH2COOR

S

(51) R = Me or Et

(EtO)zP-SCH2COOR

(53)

Cl-P,

O2cat.

;

* (Et0)2P-CH2COOR (54)

(52)

3: Tervalent Phosphom Acid Derivatives

87

Proline or sarcosine with dichloro(diethy1amino)phosphine gave thermally unstable 1,3,2-oxazaphospholanes,e.g. (56).41A number of 1,3,2-thiazaphospholanes (57) have been prepared from mercaptoacetamides,42and 1,3,4,2-thiadiazaphospholenes (58) from thi~hydrazides.~~ Ylidylphosphinidene chalcogenides (59) failed to give the Wittig products (60), but gave instead the P-ylidyl-1,3,2oxathia(se1ena)phospholes (61).& Et3N

+

COONa

C12PNEt2

H

P-0

EtpN

0

R'

R '

N-N 'P-X

R2--(

Y)-X

S'

(58) R' = Pr' or Ph R2 = CH2Ph, Ar, or SMe X = CI Or NRp

(57) R = H, Me, Et, or Ph X = CI, OR, or NR2

X

T

A

r

0 (59)

R = Et Or CI

Y=SorSe

A series of 1,3,2-oxazaphosphorinanes(62) has been prepared for conformational studies.45 Some new seven-membered ring phosphoramidites (63)46 and diamidites (64)47have been synthesised.

Mechanistic Studies. - A kinetic study of the solvolysis of the cyclic phosphoramidite (65) in methanol at 40°C, catalysed by different amine hydrochlorides, showed that kcat obeyed the Brernsted equation with a = 0.65!* This means that a proton transfer is well advanced in the TS, which was depicted as (66). Reactions of phosphoramidites with phenols are not catalysed by amine hydrochlorides and proceed sluggishly without a solvent; aromatic solvents, e.g.

3.2

Organophosphorus Chemistry

88

(63)R', R2 = H or Me = H or Me R2 = H, Me, or But X = OMe, OCH(CF&, or NMe2

(64)R = Et or Ph

(62)R'

anisole, gave better yields, probably by diminishing phenol-phenol association^.^^ A paper describing a reaction between a simple phosphoramidite (67) and an alcohol with tetrazole added reported that, although the tetrazolide formed, no phosphite was obtained; addition of diisopropylethylamine however resulted in the expected product.50

+

X>P-NEtPh

-

MeOH RaNH'CI40 "C

X>P-OMe

Tr-S-0, NC-

/

P-NPr'z

0

1,3,2-Dioxaphospholanes are thermodynamically most stable with the Psubstituent axial due to stereoelectronic effects. The conversion of (68) to (69) with an equatorial phenoxy group has now been realised by addition of triethylamine slowly to a mixture of (68) and phenol at - 78 0C.51Reactions at room temperature gave (70) with an axial phenoxy group, and the conversion of (69) to (70) was found to be catalysed by triethylamine hydrochloride as well as by phenoxide ions, the latter via a proposed phosphoranide TS (71).

CI

'

PhOH

r.t.

OPh I

OPh

cat.

-78 "C

OPh

3: Tervalent Phosphorus Acid Derivatives

89

Pure diastereomers of the aryl nucleoside phosphites (72) have been treated with alcohols under basic conditions in order to study the stereoselectivityof the substitution reactions.52 The reactions with 2-propanol in the presence of triethylamine gave phosphites with a diastereomeric purity of up to 94%, but with 3’-benzoylthymidine the maximum purity was 86%; the results were thought to reflect competitive base-catalysed epimerisation of (72) and stereoselective substitution, but whether the substitution reactions proceeded with retention or inversion was unfortunately not investigated. In three papers, G. Just et al. have described studies on the possibility of stereoselective formation of phosphites from diastereomerically pure phosphoramidites. The phosphoramidite (73) with methanol and a variety of heterocyclic catalysts gave the highest selectivity (50: 1) with 2-bromo-4,5dicyanoimidazoleas the catalyst;53 the selectivity however dropped to 3:1 when 3’-(tert-butyldimethylsilyl)thymidinewas used instead of methanol. One pure diastereomer (74) with 3’-(tert-butyldimethylsilyl)thymidine in chloroform at - 15 “C gave a stereoselectivity of 70:l with 2-bromo-4,5dicyanoimidazole as the cataly~t.’~ The phosphoramidite (75) did not need a catalyst but gave phosphites which were single diastereomers when treated with alcohols, e.g. 5’-(tert-butyldimethylsilyl)thymidine in dichloromethane at room temperature for 30 min.55

3.3

Use for Nucleotide, Sugar Phosphate, Phospholipid, or Phosphoprotein

Synthesis. - The ally1 diethylphosphoramidochloridite (76) could be purified by

distillation in contrast to the diisopropyl analogue, and used for the preparation of nucleoside pho~phoramidites.~~ The hexafluoroisobutyl analogue (77) gave nucleoside phosphoramidites which were as reactive as the conventional 2cyanoethyl diisopr~pylphosphoramidites.~~ A new phosphorodiamidite (78) has been proposed for in situ preparation of nucleoside pho~phoramidites;~~ however, the nitrotriazole formed must be neutralised by the addition of a tertiary amine in order to suppress 3’,3’-dimer formation. Bis(2-cyano-l , 1-dimethylethyl) diethylphosphoramidite(79) has been prepared and used without purification to phosphitylate ribonucle~sides.~~ The bis(5’-acyl-2-thioethyl) phosphoramidites (80) were used to obtain bis(SATE) phosphortriester derivatives of AZT for prodrug studies.60

90

Organophosphorus Chemistry

(76)R = allyl (77) R = CH2CH(CF&

(" (NC30)2P-N4

(79)

S*O)2P-NPr$ 0

(80) R = Me, Pr', But, or Ph

Three papers have appeared this year disclosing new phosphoramidite reagents for the chemical 5'-phosphorylation of oligonucleotides. All three reagents, (81),6' (82),62and (83)63 contain a lipophilic group which allows easy reversephase HPLC purification of the phosphorylated products. The subsequent removal of the lipophilic and other groups to give the free 5'-phosphate substituted oligonucleotide is effected with acetic acid followed by methylamine for (81), hydrogen peroxide followed by base for (82), and photolysis for (83). The reagent (83) furthermore allows affinity purification on a streptavidin column due to the presence in (83) of a biotin moiety. A phosphoramidite (84) has been designed for use as a photocleavable DNA building block.64 Another phosphoramidite (85) was made as an optimised linker for stabilisation of a DNA duplex by bridging the 3'-end of one strand with the 5'-end of the other strand.65 Two phosphoramidites (86) were used for the preparation of 0phosphorylated serine, threonine, and tyrosine monomers useful for Boc solidphase peptide synthesis.66Nucleoside 1,3,2-oxazaphospholidines(87) have been evaluated as phosphoramidite synthons in oligonucleotide synthesis.67 These monomers required a slightly longer coupling time, but behaved in all other respects like the usual nucleoside 2-cyanoethyl diisopropylphosphoramidites,and

0 Me

(CH2)4CONH(CH2)&ONHCH;

NPr's

3: Tervalent Phosphorus Acid Derivatives

91

DMTrO

(84)

(86) R

DMT*Y

=a

Me

0,

!-I(

or - C H 2-0 N 4

gave phosphordiester linkages without any trace of phosphoramidates after a conventional ammonia treatment. Several routes to the versatile nucleoside phosphite (88) have been examined and an effective route identified.68 0

BSA

II

RO-P-OCOCMe3 I H

-

OSiMe3 RO-P, OCOCMe3

quindine. MeCN

(88) R - St-DMTrdT3'-yl

A peptide-oligonucleotideconjugate has been prepared by phosphitylation of a primary carboxamide with 2-cyanoethyl diisopropylphosphoramidochloridite to give the N-acyl phosphordiamidite (89);69 no phosphitylation occurred at the internal secondary amide groups, and the phosphoramidate linkage was sufficiently stable to allow deprotection of the conjugate by standard methods. The phosphitylation occurred at the nitrogen, and not the oxygen, atom of the carboxamide, as shown by NMR data for a model compound Some NPr'2

NPr'2 Ac-Ser-Gly-Asp(0Fm)-N HOAc I

6

PhCH2CONH-P jO/\/CN

'O-/CN

(90) Sp 117 ppm

(89)

0- P,

0 (91) R = alkyl or acyl

c15H31cmI 0-P\

,NPNPNo2 /

c15H31coo

(92)

92

Organophosphorus Chemistry

nucleoside-phospholipid conjugates have been prepared using phosphoramidites (91) or (92) derived from lipids.70A platelet activating factor analogue (93) has been made by two routes, the best being the one shown which begins with the reaction of a sulfenyl chloride with a 1,3,2-dioxaphospholane (94).71 New glycosylphosphonates, e.g. (99, were prepared in good yields from phosphites, e.g. (96), and dimethyl trimethylsilyl phosphite, catalysed by trimethylsilyl t~iflate.~~

+

-

O=P(OMe)2

(Me0)2P--OSiMe3 MeSiOTf AcNH, f - - & W O O M e

Acd

(95)

New thiol-linker reagents (97) for the labelling of oligonucleotides have been published.73 Two achiral phosphoramidites (98) and (99) for the multiple The phosphoramidites labelling of oligonucleotides have been ~ynthesised.~~ (100) for multiple labelling or branching of oligonucleotides, and a biotin

AH0--

OMTrO

p\o/VCN

(97) R = Me or Ph L

N

H

R

(98) R = COCF3, Fmoc, or Dansyl

(99) R = COCF3, Fmoc, MMTr, or CO(CH2)5NHCOCF3

3: Tervalent Phosphorus Acid Derivatives DMTrO(CH2)& O N H 7

93 NPr'2

+"-%-CN DMTrO(CH&CONH (100) n = 3 or 11 0

phosphoramidite (101) which gives stereohomogeneous conjugates, have been described.75 An acridine phosphoramidite (102), which gives oligonucleotide conjugates that are stable to the usual deprotection conditions, has been ~repared.'~Several phosphoramidites of benzophenanthridine, e.g. (103), were prepared for a study of oligonucleotide-intercalator conjugate^.^^ A convenient way to prepare hapten phosphoramidites, e.g. (104), in large scale has been developed.78A new pyrene phosphoramidite (105) allows multiple labelling of oligonucleotides with ~ y r e n eOligonucleotides .~~ have been labelled with redoxactive ferrocenyl groups by using the ferrocenylalkylphosphoramidite (106).*O A series of nucleoside alkyl phosphoramidites (107) containing lipophilic alkyl groups has been prepared and used to synthesise oligonucleotides with lipophilic thiophosphotriester linkages.81A full paper has appeared on the preparation of phosphorodithioate DNA from thiophosphoramidites (108) containing base labile S-protection groups.**The thiocarbonate derivatives (108, R = alkylO- or arylO-) gave more biproducts than the thiocarboxylate derivatives, of which the

94

Organophosphorus Chemistry

H & ' ODMTr

thiobenzoate derivatives (108, R = Ph) gave the best results. The origin of the phosphorothioate impurities was discussed in detail, and conditions, in particular deprotection conditions, improved to give 2-5% phosphorothioates routinely and down to about 1% in the best cases. Oligonucleotides containing benzylphosSome phonate linkages have been prepared from the phosphonamidites ( dinucleoside phosphorofluoridites (1 10) were prepared from (1 11) and could be separated into pure diastereomers by column ~hromatography.~~ The first synthesis of nucleoside phosphorofluoridothioates(1 12) has been realised starting from (1 1l).85 A new type of oligonucleotide analogue (1 13), containing N-acylphosphoramidate linkages, has been prepared from the thymine monomer (1 14).86 Reports of the use of the alkylphosphonamidites (1 15)87 or (1 16)88 for the preparation of alkylphosphonopeptides have appeared. NPri2

@(cHz)sO-p?

O-cN

DMTaY O,

P-N Pr',

Rd

(107) R = Et, Pr', CI6H3, 1-adamantyl, or 6-(cholesteryl-3-oxycarbo11ylamino)hexyl

DMTav DMT* 0

(108) R = alkyl, avl, alkylO, or arylO

3: Tervalent Phosphorus Acid Derivatives

95

DMTav """Y DMTav 3I-DMTrdT

tetrazol

*

NEt2 Me-P,

OBu'

4p -o'ph

$

NPr$ 'O-CH*

-0Me

(116) R = Me or octyl

3.4 Miscellaneous. - New chiral tervalent phosphorus acid derivatives for enantiopurity determinations by 31P NMR are (117), used for ahydro~yalkylphosphonates,~~ and (1 1s),useful for diamines and diols.gO

I

Chiral ligands containing tervalent phosphorus acid derivatives as coordination sites continue to be explored for asymmetric metal catalysed reactions. New examples this year include the phosphite (119) and stereoisomers?l the phosphites (uO),~* the diphosphinite 'TADDOP' (121),93 the diphosphites (122) containing crown ethers,% the aminophosphine-phosphinites'AMPP's (123) and ( 1 2 4 p the phosphetane (125p6 the aminophosphine-phosphinite 'PINDOPHOS' (1 26),97 and the bisaminophosphines 'BAMP' (127).98

Organophosphoru Chemistry

96

g o \ P - O Q0'P P h 2

\

/

c 7

c 7

ono

ono

Ph

LYJ

Ph

xfo-pph2 h-O-

Ph

PPh2

Ph

(122) R = H or Me

=-c>

(123) R' = Me or CH2Ph (124) R1 R2 = Me or Ph R 3 = a orPh R 2 = a

Or

A Ph

orPh

(125)

3: Tervalent Phosphorus Acid Derivatives

4

97

Reactions Involving Two-co-ordinate Phosphorus

The 4,5-dioxo-l,3,2-dioxaphospholane (128) has been prepared and subjected to thermal or MS frag~nentation;~~ an intense peak corresponding to (129) was found in the EI mass spectrum, and thermolysis gave (130), both results in accordance with a facile formation of the arylphosphinidene oxide (129) from (128). Pyrolysis of the cyclic phosphites (131) gave a deposit on a - 195"C cold finger which according to 31PNMR contained some aryl phosphenite (132), the chemistry of which could be studied for the first time.lm A full paper has appeared on the preparation and properties of the stable ylidylphosphinidene chalcogenides (133).1°'

COOAg .PCI*+ I COOAg

(128)

OAr I

/\

I

R

0 I

b

ArO-P=O

A r o " ~ ~ \ o A r ( 132)

Ph3P

(133) R = alkyl, aryl, or Me3Si X = S or Se

X = Me, But, or OMe

The iminophosphine (134)with 1-alkynesgave various products of 1,l- or 1,2additions.lo2 A new synthesis of diphosphenes (135) from aryldichlorophosphines and a tungsten complex has been described;lo3the tungsten complex catalysed an exchange between two diphosphenes to give the unsymmetric diphosphene. A ferrocenyl-substituted diphospliene (136) has been prepared which seems to thus the dimer (137) represent a borderline case with respect to dimerisation;l@' readily dissociates to (136)upon heating in xylene.

98

Organophosphorus Chemistry

The first example of a phosphenium ion (138) with a P-C single bond has been prepared and characterised by X-ray crystallography.lo5 An X-ray structural study of the phosphenium tetraphenylborate (1 39) showed a phosphenium ion without cation-anioninteractions.lo6

But I N MqSi< ;P+ N P+-AICls

I

But

Ph4B-

3: Tervalent Phosphow Acid Derivatives

99 R'p" 0

-e-

PhP(OR)2

c

Ph'

0 2

(140) R = Me or Et

(R10)3P

+

O 'R

(141)

0

TeC14

R2SH

(R'0)2P,

base

//

SR2 (142) R' = alkyl

R2 = alkyl or aryl

ONa A3

(143)

( Q)

%

3P=NSiMe3

3

b;L( Me3Si

Me,

N ,

/

N

I

N

N

\

A3

(144)

(Pri2N)2P-C-P(NPr$)2 ** +

CF3SO3-

I H

Miscellaneous Reactions

5

Dialkyl phenylphosphinites (140) undergo intramolecular Arbuzov rearrangements upon electrolysis at the anode in the presence of oxygen in acetonitrile to give phosphinates (141).107Trialkyl phosphites and alkanethiols or thiophenols, in the presence of tellurium tetrachloride and a base, gave high yields of phosphorothioates (142).lo8 The reaction of 2-haloaryl phosphinites (143) with sodium gave the rearranged products (144), or diphosphines or phosphides, depending on the type of halogen and the substituents on phosphorus.10gThe iminophosphorane (145) with methyllithium surprisingly gave the lithium complex of an aminophosphine (146).11* A full paper has appeared on the preparation and reactions of phosphino-phosphonio carbenes, e.g. (147)' References 1.

'Proceedings of the Thirteenth International Conference on Phosphorus Chemistry', ed. E. Breuer, Phosphorus, Surfur, Silicon, 1996,109-110.

100 2. 3. 4. 5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27.

28. 29. 30. 31. 32. 33. 34. 35.

Organophosphorus Chemistry 0. Dahl, in ‘The chemistry of organophosphorus compounds’, ed. F. R. Hartley, John Wiley & Sons, Chichester 1996, vol. 4, p. 1-45. ‘Comprehensive Heterocyclic Chemistry II’, ed.-in-chief A. R. Katritzky, C. W. Rees, and E. F. V. Scriven, Elsevier Science, Oxford 1996. W. Froestl, S. J. Mickel, R. G. Hall, G. Vonsprecher, D. Strub, P. A. Baumann, F. Brugger, C. Gentsch, J. Jaekel, H. R. Olpe, G. Rihs, A. Vassout, P. C. Waldmeier, and H. Bittiger, J. Med Chem., 1995,38,3297. W. Froestl, S.J. Mickel, G. Vonsprecher, P. J. Diel, R. G. Hall, L. Maier, D. Strub, V. Melillo, P. A. Baumann, R. Bernasconi, C. Gentsch, K. Hauser, J. Jaekel, G. Karlsson, K. Klebs, L. Maitre, C. Marescaux, M. F. Pozza, M. Schmutz, M. W. Steinmann, H. Vanriezen, A. Vassout, C. Mondadori, H. R. Olpe, P. C.Waldemeier, and H. Bittiger, J. Med. Chem., 1995,38,3313. C. Bergin, R. Hamilton, B. Walker, and B. J. Walker, Chem. Commun., 1996, 1155. J.-L. Montchamp, F. Tian, and J. W. Frost, J. Org. Chem., 1995,60,6076. W. Henderson, A. G. Oliver, and A. J. Downard, Polyhedron, 1996,15,1165. C. Maury, T. Gharbaoui, J. Royer, and H.-P. Husson, J. Org. Chem., 1996, 61, 3687. E. A. Boyd, W. C. Chan, and V. M. Loh Jr, Tetrahedron Lett., 1996,37,1647. S. Yamago, M. Yanagawa, H. Mukai, and E. Nakamura, Tetrahedron, 1996, 52, 5091. E. A. Boyd, M. E. K. Boyd, and V. M. Loh Jr, Tetrahedron Lett., 1996,37, 1651. A. Bongini, R. Camerini, and M. Panunzio, Tetrahedron-Asymmetry,1996,7, 1467. E. Bandini, G. Martelli, G. Spunta, and M. Panunzio, Tetrahedron-Asymmetry, 1995,6,2127. M. Sugiura, K. Asai, and Y . Hamada, Heterocycles, 1996,43,953. B. A. DSa, and J. G. Verkade, J. Org. Chem., 1996,61,2963. R. Hulst, A. van Basten, K. Fitzpatrick, and R. M. Kellogg, J. Chem. Soc., Perkin Trans. I , 1995,2961. S . Strojek, and M. Jansen, Chem. Ber., 1996,129,121. V. A. Efimov, A. L. Kalinkina, 0. G. Chakhcheva, T.S. Hill, and K. Jayaraman, Nucleic Acids Res., 1995,23,4029. Q. Xu, K. Musier-Forsyth, R. P. Hammer, and G. Barany, Nucleic Acids Res., 1996, 24,1602. N. Bricklebank, S. M. Godfrey, H. P. Lane, C. A. McAuliffe, R. G. Pritchard, and J.-M. Moreno, J Chem. Soc.. Dalton Trans., 1995,2421. 0.I. Kolodyazhnyi, and 0. R. Golovatyi, Rurs. J. Gen. Chem., 1995,65,295. M. de F. Fernandez, C. P. Vlaar, H. Fan, Y.-H. Liu, F. R. Fronczek, and R. P. Hammer, J. Org. Chem., 1995,60,7390. I. D. Grice, P. J. Harvey, I. D. Jenkins, M. J. Gallagher, and M. G. Ranasinghe, Tetrahedron Lett., 1996,37, 1087. A. Longeau, F. Langer, and P . Knochel, Tetrahedron Lett., 1996,37,2209. K. G. Moloy, and J. L. Petersen, J. Am. Chem. Soc., 1995,117,7696. A. Frenzel, M. Gluth, R. Herbstirmer, and U.Klingebiel, J. Orgunometal. Chem., 1996, 514,281. V. S. Reddy, and K.V. Katti, 2.Anorg. Allgem. Chem., 1995,621,1939. V. S . Reddy, K.V. Katti, and C. L. Barnes, Inorg. Chem., 1995,34,5483. I. Shevchenko,H. Zhang, and M. Lattman, Inorg. Chem., 1995,34,5405. F. J. Parlevliet, A. Olivier, W. G. J. de Lange, P. C.J. Kamer, H. Kooijman, A. L. S p k , and P. W.N. M. van Leuwen, Chem. Commun.,1996,583. V . I. Maslennikova, E. V. Panina, A. R. Bekker, L. K. Vasyanina, and E. E. Nifant’ev, Phosphorus, Sulfur, Silicon, 1996,113,219. E. E. Nifant’ev, R. K.Magdeeva, R. M. Syaribzhanova, and L. K.Vasyanina, Russ. J. Gen. Chem., 1995,65,287. C. Bengourina, G. Cordonnier, and H. Sliwa, Syn. Commun.,1996,26,2383. Y. I. Blokhin, D. V. Gusev, V. K. Belsky, A. I. Stash, and E. I. Nifantyev, Phosphorus, Sulfur, Silicon, 1995,102,143.

3: Tervalent Phosphorus Acid Derivatives 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51.

101

E. N. Rasadkina, N. S. Magomedova, V. K. Bel’skii, and E. E. Nifant’ev, Russ. J. Gen. Chem., 1995,65,182. Y. I. Blokhin, F. M. Galiaskarova, M. Y. Ergashov, M. Y. Antipin, Y. T. Struchkov, and E.E. Nifant’ev, Russ.J. Gen. Chem., 1995,65, 178. E. N. Rasadkina, E. V. Ronkova, V. K.Bel’sky, and E. E. Nifant’ev, Russ. J. Gen. Chem., 1995,65,1213. A. R. Burilov, A. A. Barullin, and M. A. Pudovik, Russ.J. Gen. Chem., 1995,65,324. I. E. Nifant’ev, L. F. Manzhukova, M. Y. Antipin, Y. T. Struchkov, and E. E. Nifant’ev, Russ. J. Gem Chem., 1995,65,682. E. E. Nifant’ev, S.Y.Burmistrov, M. K. Grachev, and A. R. Becker, Russ. J. Gen. Chem., 1995,65,1282. M. Weber, and I. Ugi, Liebigs Ann., 1995,1555. T. B. Huang, and J. L. Zhang, Phosphorus, Sulfur,Silicon, 1995,104,33. A. Schmidpeter,S. Plank, and K. Polborn, 2.Naturforsch., 1995, Sob, 1543. Y. Huang, J. Yu, and W. G. Bentrude, J. Org. Chem., 1995,60,4767. E. E. Nifant’ev, D. A. Predvoditelev, M. A. Malenkovskaya, A. R. Bekker, N. S. Magomedova, and V. K. Bel’skii, Russ.J. Gen. Chem., 1995,65,328. A. I. Zavalishina, N. N. Nurkulov, E. I. Orzhekovskaya, A. R. Bekker, L. K. Vasyanina, I. B. Bespalova, and E. E. Nifant’ev, Russ. J. Gen. Chem., 1995,65,701. S . Y. Bunnistrov, N. M. Shchedrova, M. K. Grachev, L. K. Vasyanina, and E. E. Nifant’ev, Russ.J. Gen. Chem., 1995,65,500. F. M. Galiaskarova, L. K. Vasyanina, Y. I. Blokhin, and E. E. Nifant’ev, Russ. J. Gen. Chem., 1995,65,286. K. J. Percival, and C.W.G. Fishwick, Nucleosides Nucleotides, 1995,14, 1785. B. Gordillo, C. Garduno, G. Guadarrama, and J. Hernandez, J. Org. Chem., 1995, 60,5180.

52. 53. 54. 55. 56.

M. Mizuguchi, and K.Makino, NucleosidesNucleotides, 1996,15,#7. Z . Xin, and G. Just, TetrahedronLett., 1996,37,969. Y . Jin, G. Biancotto, and G. Just, Tetrahedron Lett., 1996,37,973. E. Marsault, and G. Just, Tetrahedron Lett., 1996,37,977. M. C . Pirrung, L. Fallon, D. C. Lever, and S. W. Shuey, J. Org. Chem., 1996,61, 2129.

57. 58. 59. 60. 61. 62. 63.

S.-G.Kim, K.Eida, and H. Takaku, Bioorg. Med Chem. Lett., 1995,5,1663. Z . Zhang, and J. Y .Tang, Tetrahedron Lett., 1996,37,331. M. Sekine, H.Tsuruoka, S. Iimura, H. Kusuoku, T. Wada, and K. Furusawa, J. Org. Chem., 1996,61,4087. I. Lefebvre, C. Perigaud, A. Pompon, A.-M. Aubertin, J.-L. Girardet, A. Kirn, G. Gosselin, and J.-L. Imbach, J. Med Chem., 1995,38,3941. A. Guzaev, H. Salo, A. Azhayev, and H. Liinnberg, Tetrahedron, 1995,51,9375. C. Garcia-Echeverria,and R. Hiher, Tetrahedron, 1996,52,3933. J. Olejnik, E. Knymanska-Olejnik, and K. J. Rothschild, Nucleic Acids Res., 1996, 24,361.

66.

P. Ordoukhanian, and J.-S. Taylor, J. Am. Chem. SOC.,1995,117,9570. S . Altmann, A. M. Labhardt, D. Bur, C. Lehmann, W. Bannwarth, M. Billeter, K. Wiithrich, and W . Leupin, Nucleic Acidr Res., 1995,23,4827. T.Wakamiya, K. Saruta, J. Yasuoka, and S . Kusumoto, Bull. Chem. SOC.Japan,

67. 68. 69. 70. 71. 72. 73.

R. P. Iyer, D. Yu, T. Devlin, N.-H. Ho, and S . Agrawal,J. Org. Chem., 1995,60,5388. R. Zain, and J. Stawinski, J. Chem. SOC.,Perkin Trans. 2, 1996,795. J. Robles, E. Pedroso, and A. Grandas, J. Org. Chem., 1995,60,4856. H. Sigmund, and W. Pfleiderer, Helv. Chim. Acta, 1996,79,426. B. Mlotkowska, and J. Olejnik, Liebigs Ann., 1995,1463. M. Imamura, and H. Hashimoto, Terrahedron Lett., 1996,37,1451. P. Kumar, D. Bhatia, R. C . Rastogi, and K. C. Gupta, Bioorg. Med. Chem. Lett.,

74.

A. Guzaev, H.Salo, A. Azhayev, and H. Liinnberg,Bioconjugate Chem., 1996,7,240.

64. 65.

1995,68,2699.

1996,6,683.

102

Organophosphorus Chemistry

75.

V. A. Korshun, N. B. Pestov, E. V. Nozhevnikova, 1. A. Prokhorenko, S. V. Gontarev, and Y. A. Berlin, Syn. Commun., 1996,26,2531. K. Schiitz, M. Kurz, and M. W. Gobel, TetrahedronLett., 1995,36,8407. J. Chen, H. L. Weith, R. S. Grewal, G. Wang, and M. Cushman, Bioconjugute

76. 77. 78. 79. 80.

Chem., 1995, 6,473. J. R. Fino, P. G. Mattingly, and K. A. Ray, Bioconjugate Chem., 1996,7,274. I. A. Prokhorenko, V. A. Korshun, A. A. Petrov, S. V. Gontarev, and Y. A. Berlin, Bioorg. Med Chem. Lett., 1995,5,2081. R. C . Mucic, M. K. Herrlein, C. A. Mirkin, and R. L. Letsinger, Chem. Commun., 1996,555.

99.

Z. Zhang, J. X.Tang, and J. Y .Tang, Bioorg. Med. Chem. Lett., 1995,5,1735. W. T. Wiesler, and M. H. Caruthers, J. Org. Chem., 1996,61,4272. W. Samstag, S. Eisenhardt, W. B. Offensperger, and J. W. Engels, Antisense & Nucleic Acid Drug Development, 1996,6, 153. W. Dabkowski, I. Tworowska, J. Michalski, and F. Cramer, J. Chem. Soc., Chem. Commun., 1995,1435. W. Dabkowski, and I. Tworowska, Chem. Lett., 1995,727. D. Filippov, N. J. Meeuwenoord, G. A. van der Marel, V. A. Efimov, E. KuylYeheskiely,and J. H. van Boom, Synlett., 1996,769. R. Hoffmann, A. Tholey, T. Hoffmann, and H. R. Kalbitzer, Int. J. Peptide Prot. Res., 1996, 47,245. J. C. H. M. Wijkmans, N. J. Meeuwenoord, W. Bloemhoff, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 1996,52,2103. P. G. Devitt, M. C. Mitchell, J. M. Weetman, R. J. Taylor, and T. P. Kee, Tetrahedron-Asymmetry, 1995,6,2039. J. M. Brunel, and B. Faure, Tetrahedron-Asymmetry, 1995,6,2353. A. Kless, J. Holz, D. Heller, R. Kadyrov, R. Selke, C. Fischer, and A. Borner, Tetrahedron-Asymmetry, 1996,7, 33. J. Scherer, G. Huttner, and M. Biichner, Chem. Ber., 1996,129,697. D. Seebach, E. Devaquet, A. Emst, M. Hayakawa, F. N. M. Kiihnle, W. B. Schweizer,and B. Weber, Helv. Chim. Acta, 1995,78, 1636. D. K. Macfarland, and C. R. Landis, Organometallics, 1996,15,483. A. Roucoux, L. Thieffry, J. F. Carpentier, M. Devocelle, C. Meliet, F. Agbossou, and A. Mortreux, Organometallics, 1996,15,2440. A. Marinetti, C. Lemenn, and L. Ricard, Organometallics, 1995,14,4983. H. J. Kreuzfeld, U. Schmidt, C. Dobler, and H. W. Krause, Tetrahedron-Asymmetry, 1996, 7 , 1011. A. ROUCOUX, I. Suisse, M. Devocelle, J. F. Carpentier, F. Agbossou, and A. Mortreux, Tetrahedron-Asymmetry, 1996,7,379. A. H. Cowley, F. P.Gabbdi, S. Corbelin, and A. Decken, Inorg. Chem., 1995, 34,

100. 101.

L.D. Quin, and A. S . Ionkin, J. Org. Chem., 1995,60,5186. G. Jochem, K. Karaghiosoff, S. Plank, S. Dick, and A. Schmidpeter, Chem. Ber.,

102. 103.

A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova, and I. P. Beletskaya, Zh.Org. K h h . , 1996,32,433. K. B. Dillon, V. C. Gibson, and L. J. Sequeira, J. Chem. SOC.,Chem. Commun.,

104. 105. 106. 107. 108. 109. 110. 111.

R. Pietschnig, and E. Niecke, Organometallics, 1996,15,891. R. W. Reed, Z. W. Xie, and C . A. Reed, Organometallics, 1995,14,5002. M. Veith, W. Kruhs, and V . Huch, Phosphorus, Sulfur,Silicon, 1995,105,217. S. Yasvi, K.Shioji, M. Tsujimoto, and A. Ohno, Tetrahedron Lett., 1996,37, 1625. Y. Watanabe, S. Inoue, T. Yamamoto, and S . Ozaki, Synthesis, 1995,1243. J. Heinicke, and R. Kadyrov, J. Organometal. Chem., 1996,520,13 1. A. Steiner, and D. Stalke, Angew. Chem.. Int. Ed Engl., 1995,34,1752. P. Dyer, A. Baceiredo, and G. Bertrand, Znorg. Chem., 1996,35,46.

81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98.

5931. 1995, 128,1207.

1995,2429.

4 Quinquevalent Phosphorus Acids BY R. S.EDMUNDSON

1

Introduction

This year has seen an even greater emphasis on studies related to phosphonic and phosphinic acid derivatives, relative to those on phosphoric acids. A large amount of 'H, I3C, and "P NMR spectroscopic data has accumulated, and the use of such data in the confirmation of structures, as well as that of X-ray diffraction techniques, continues to be widespread. 2

Phosphoric Acids and their Derivatives

2.1 Synthesis of Phosphoric Acids and their Derivatives. - Further experimental results concerned with the direct formation of such compounds from elemental phosphorus have been reported and the kinetics and mechanisms of such reactions studied. A reagent consisting of iodine-sodium nitrite converts red phosphorus together with phenol in a solvent (dioxane, toluene, or pyridine) at 60-80°C into triphenyl phosphate and iodobenzene;' under the same or similar conditions, low molecular weight alcohols are converted into mixtures of trialkyl phosphates and dialkyl hydrogenphosphonates.2 The latter products also result from the use of sodium hypophosphite with similar systems containing copper(I1) chloride; the yields can be very high for low molecular weight alcohols but decrease with increasing molecular weight of the Alternatively, the electrolysis of a suspension of emulsified white phosphorus in MeCN containing the alcohol and phenothiazine produces 30-70% of the dialkyl hydrogenphosphonatebut only poor to moderate yields (
103

104

Organophosphorus Chemistry

(1) Z =CH2

(3)

z=s

(2)

(4)

represent the binaphthalenyl moiety of (R)configuration and A has the significance indicated in (6) and (7), are of interest. The syntheses of (6) and (7) were achieved by the coupling of appropriate acetylenic precursors. The most interesting feature of the two molecules resides in their ‘interior’ molecular dimensions; the cavity in compound (6), as represented by the di?tance between the phosphorus atoms, is square ip cross-section and of side 7.2 A and that in (7) is rectangular, being 7.2 x 11.6 A. These dimensions enable compound (6) to bind with suitably sized monosaccharides to form 1:l adducts, whereas (7)binds with disaccharides but not with monosaccharides because of their inability to hydrogen-bond satisfactorily.l 3

2-A-2

I

A

I

2-A-2

I

Z=

A

I

Interest in phosphate derivatives of the calixarenes continues to grow, and some novel transformations have been shown to be feasible following the phosphorylation of the calix[4]arene (8) (n = 0; R1--R4 = OH) and the calix[6]arene (8) (n = 1; R’ -R6 = OH) with reagents such as (Et0)2P(0)CI, and during which the phosphorylation reaction may, or may not, proceed to completion. Thus, the first substrate undergoes reaction only as far as the triphosphorylated product, the structure of which was confirmed by X-ray diffraction experiments; the diphosphorylated compound (9), when acted upon by NaH, forms a monoanion which rearranges to the monoanion of (1 0). l4 The mono-, di(two), tri-(one), and hexa-(diethoxyphosphnoylated) derivatives of the above calix[6]arene have also been obtained.” Free dihydrogenphosphates based upon the calix[4]arene system (8) have been recorded.I6

4: Quinquevalent Phosphorus Acidr

105

The ability of the calix[4]arene system to form cyclic phosphates has been demonstrated. When acted upon by PC15, calixarene (8) (n = 0, R' -R4 = OH) yields the intermediate (1 1) as its hexachlorophosphate salt; a reaction between the latter and water gave (12), probably via (13); with EtOH, (11) yields (14). Other simple, analogous compounds were also reported.l7 The initial product from the reaction between PCls and the calix[6]arene (8) (n = 1; R' -R6 = OH) was the salt (19, hydrolysable to the bisbicyclic phosphate (16). l 8 Pyrolysis (at just above the melting point) of the distally diphosphorylated compound (9),and of the proximal diphosphate (lo), and also of the tetraphosphate, as well as of other compounds such as the trichloride (13), afforded the pyrophosphate (13, the structure of which was also confirmed by X-ray diffraction.'* The pyrolysis of partially phosphorylated derivatives of the tert-butylcalix[6]arene also gave the bisbicyclic phosphate (16). l 8

(8)

(9) = (8);I/ = 0, R' = R3 = OH, R2 = R4 = ( E t 0 ) p P(0) (10) = (8);IJ = 0, R' = R2 = OH, R3 = R4 = (Et0)2 P(0) (11) = (8);n = 0, R1R2R3= 0 3 h , R4 = 0PCl4 (12) = (8);n = 0, R'R2R3 = OsP(O), R4 = OPO3H2

(13) = (8); n = 0, R' = OH, R2R3 = OzP(O)CI, R4 = OP(O)Cl2 (14) (8);n = 0, R'R2R3 = OsP(O), R4 = OP03Et2 (15) = (8);n = 1, R1R2R3= R4R5R6= 0 3 k

(16) = (8); n = 1, R1R2R3= R4R5R6 = 03P(0)

The water-soluble distally phosphorylated calix[4]arenes (18) have been deas has the fully phosphorylated (19).21 The chemistry and mode of biochemical action of inositol phosphates have been reviewed (with 513 references).22In the comparatively little work on inositol phosphates which has been published during the year, it is evident that in the phosphorylation stage(s), phosphorylation through phosphitylation continues to be the procedure of choice. In this respect, diethyl chlorophosphite was employed in the conversion of myo-inositol into all twelve regioisomeric myo-inositol tris(dihydrogenph0sphates) through the isomeric tribenzoates and in high overall yields, and it is now possible to prepare all 39 regioisomeric inositol phosphates through initial acyl group migration^.^^ Acyclic or cyclic phosphoramidites, or acyclic phosphorodiamiditeshave been employed in the preparation of 1-0-alkyl-

106

Organophosphorus Chemistry

+

(18) R = Me, pentyl or heptyl,

R'

= H or(Et0)2P(0), R2 = H

(19) R P undecyl, R1 = R2 = ( Et0)2P(0)

and 1-0-acyl-myo-inositol 3,4,5-tris(dihydrogen phosphate)^^^ and L-chiro-inositol 1,2,3-tris- and 1,2,3,Stetrakis(dihydrogen phosphate)^.^^ The phosphitylation of (20) (R = 4-methoxybenzyl) leads to the diastereoisomers (21) and these, with 2,3-dichloro-5,6-dicyano1 ,dbenzoquinone (DDQ), yield (22); phosphorylation of the latter has given (23), and debenzylation of this with Na-NH3(1)gives a cyclic analogue (24) of an inositol triphosphate.26 OR'

4: Quinquevalent Phosphorus Acids

107

D-2-Deoxy-myo-inositol 1,3,4,5-tetrakis(dihydrogen phosphate) has been obtained from D-glucos$' and the synthesis and properties of racemic 6-deoxy6-fluoro-myo-inositol 1,4,5-tris(dihydrogenphosphate) have also been reported.28 3,4,5,6-Tetra-O-benzyl-myo-inositol is a starting point for syntheses of the 2deoxy-2-thio compound (25) and its stereoisomer, 2-deoxy-2-thio-scyZZo-inositol 1-dihydr~genphosphate.~~ Inositol monophosphatase catalyses the hydrolysis of a range of phosphate esters of inositol, and in so doing, participates in brain cell chemistry and is believed to be the target for lithium therapy. In the search for inhibitors of the enzyme, phosphate derivatives from 6-O-(2'-hydroxyethyl)cyclohexane-1,2,4,6tetraol have been prepared, the racemic epoxide (26)acting as a key intermediate. The conversion of (26) into the racernic l-phosphate (29) via (27) and (28) employed the steps indicated in Scheme 1. Further, the racefnic alcohol (27) was

Bnocf I0

OBn

OR2

(27)R'

(26)

= R2 = Bn, R3 = H

(28) R' = R2 = Bn, R3 = (Bn0)2P(O)

I-

(29) R' = R2 = H, R3 = P032'

3ii, iii

2 2

iv

(30) R' = (Bn0)2P(O), R2 = Bn, R3 = H

vi,ii

(31) R' = POs2-, R2 = R3 = H

iv

(32) R' = CH2C6H4OMe-4, R2 = Bn, R3= (PhO),P(O)

-

vii viii

OR2

(33) R' (34) R'

= =

Ph, R2 = Bn R2 = H

-

Reagents: i, BnOCH2CH20H, BFyEt20; ii, (PhO)2P(O)Cl, NEt3, DMAP, CH2C12; iii, BnOH, NaH, DMF; iv, Na, NH3; v, HOC2H40P(0)(OBn)2, BF30Et20; vi, HOC2H40CH2C6H40Me-4; vii, DDQ, CH2C12; viii, NaH, THF

Scheme 1

Organophosphorus Chemistry

108

resolved through its (1S,4R)-camphanate esters, the least polar of which was demonstrated, by X-ray diffraction, to have the (1R,2S,4R,6S) configuration; the separated camphanates were hydrolysed and the products made to yield the enantiomers of (29). The epoxide (26) also provided the phosphate (30), convertible into (31). Finally, (26) generated (32) which ultimately afforded the cyclic phosphate (34), as its phosphate anion, via (33).30 The cyclic diphosphate (35) was recently discovered (in 1983) in methanogenic archae, and its chemical synthesis has now been achieved by the action of DCC on the diphosphate (36), itself obtained from D - m a n n i t ~ l . ~ ~ 0 -027’ O

‘702Y

H203P0

O

\0p03H2

C02Me

c02-

(36)

(35)

The phosphoserine and phosphothreonine derivatives (37), building blocks for solid-phase peptide synthesis, have been prepared through phosphitylation of the allyl esters (38) and removal of the allyl ester groups from the respective (39) with Pd/NaI.32 Other derivatives were obtained through the zinc-acetic acid deesterification of 2,2,2-trichloroethyl esters with protection of the carboxy group as the phenacyl ester.33N-Phosphorylated derivatives of tyrosine have also been prepared, but some experimental conditions may lead to additional O-phosphorylation.” A two-step deprotection methodology for the N-protected 0dimethoxyphosphinoyl-serine and -threonine (40) and tyrosine (41) involves treatment with acid at two different levels, with (i) trimethylsilyl trifluoromethanesulfonate in TFA with thioanisole, cresol and ethanedithiol, and (ii), reagent (i) together with dimethyl sulfide in the same triflate ester.35

I

~ 2 * 0 ~ 3

(37)2 = Fmoc, R’ = H, R2 = H or Me, R3 = P(O)(OBn)O(38) 2 = Fmoc, R’ = CH2CH=CH2, R2 = H or Me, R3 = H

(41)

(39) Z = Fmoc, R1 = CH2CH=CH2, R2 = H or Me, R3 = P03Bn2 (40) 2 = Boc, R’ = H, R2 = H or Me, R3 P03Me2 PI

Thiophosphoryl analogues of (1) (X = S, n = 1, R = C1 or OAr)36,(2) (X = S, n = 1, R = OAr)37, and the dinaphtho analogues (3) (2 = CH2, X = S, R = OAr),38and also the compounds (4) (X = S, R = Cl)39have been prepared by conventional means. TeCb has been proposed as a catalyst in the formation of O,O,S-trialkyl or 0,O-dialkyl S-aryl phosphorothioates from trialkyl phosphites

4: Quinquevalent Phosphorus Acids

109

and thiokm Hill and Lowe have described the synthesis of phosphorothioate esters of L-phenyllactic acid, such as (42) [and thus (44)by conventional steps], by the sulfurization of the analogous hydrogenphosphonate (43).41

R;,? R200 0‘‘

_jPh C02R2

(42) R’ = SH, R2 = R3 = Bn (43) R’= H, R 2 = R 3 = B n (44)R ’ = S H , R 2 = R 3 = H

The interaction of 0,O-dialkyl phosphorodithioates with epichlorohydrin in the presence of sodium carbonate yields mixtures of the two products (45) =0 or S).42 Addition of the same dithio acids to a range of compounds (46) (Z = OEt, SMe, SBu-t, CN, SOBu-t, S02Bu-t, or I) proceeds highly regioselectively to give the corresponding (47) but, exceptionally, the addion to 1-octene (Z = pentyl) gives a mixture of the 2- and 3-phosphorylated octanes.43 (Cyclic) phosphorodithoic acids, free or as their organic salts or trimethylsilyl esters, give carbohydrate esters with peracetylated carbohydrates.&

(45)

(47)

Phosphorotetrathioic esters are obtainable from organic disulfides by the action of P4S545or P4S745*46 (although both are less reactive than P4S10); the dithiadiphosphetanes (48) convert disulfides into the esters (49) but when distilled, these decompose to give tetrathioate e ~ t e r s . 4 ~Good 9 ~ ~ yields of tetrathioate esters were also obtainable from disulfides by the action of p-P4S312.48 S

s RS-P/ ‘P-SR ‘s/I I II

S

II

(RS)2PSSR

S

2.2 Reactions of Phosphoric Acids and their Derivatives. - The rearrangement of [(trimethy1sily1)methyl] ph 0 sphates to their ethyldimethylsily1 isomers is already known; the mechanism of the process has now been examined in more detail and is thought to involve attack by phosphoryl oxygen at the silicon atom with migration of an alkyl group as indicated in Scheme 2. Diphenyl

110

Organophosphorus Chemistry

[(trialkylsilyl)methyl] phosphates at 200 “C afford mixtures of products depending on the particular migratory gro~p(s)!~

-

I

RCH2Si-0-P

I

,f \

Scheme 2

The base-catalysed rearrangement of the alkyl phosphates, particularly those possessing secondary alkyl groups, (50), into (1 -hydroxyalkyl)phosphonic esters (51) is also known, but is less well exemplified than the reverse phosphonate-tophosphate process. Only BuLi or lithium diisopropylamide may be used to deprotonate the phosphate esters (50) and then only when one (at least) of R1 and R2is aryl or alkenyi. When deprotonation occurs using amides derived from homochiral amines such as isopropyl(1-phenylethyl)amine (base A) or bis(1phenylethy1)amine (base B), deprotonation is enantioselective, implying the intermediate carbanion is configurationally stable; amides having the (S) configuration remove the pro-(S) hydrogen from (50). Thus, with @‘)-base (B) in THF, dimethyl benzyl phosphate affords ( -)-dimethyl (a-hydroxybenzy1)phosphonate with 28% e.e., whereas with (R,R)-base B, the product is the (+)-hydroxy phosphonate ester with 52% e.e. A high primary isotope effect is observed when, in (50), R’ or R2 is deuterium, km then being about 50, with the enantiomeric excesses in the appropriate hydroxy phosphonic diester being up to 85%.50

lH+

Many alkyl diphenyl esters of phosphoric acid were examined in a study of the rearrangements of compounds of the general form (52) into (53) brought about under free radical conditions by the action of tributylstannane and AIBN.5’ Typical of the examples studied is (54) (X = H) which, under normal circum-

4: Quinquevalent Phosphorus A c i h

111

stances is thermally stable ;under the influence of the reagents in boiling benzene, the only two products are those of dehalogenation, namely (55) (X = H) without rearrangement, and (56) (X = H) with rearrangement, obtained in the ratio 1:4. Likewise (54) (X = D) afforded (55) (X = D) and (56) (X = D) in the same ratio. Experimental evidence eliminated the possibility that the migration took place via (56) (X = Br) or (57). Complete selectivity of rearrangement was established through the examination of esters of several structural types. The migration is evidently intramolecular and does not involve phosphoranyl radicals. R'O,

,OR'

oOp*o

t

-

R'O, ,OR' o,,p\o

R

+

R

(52)

PhO,

,OPh

oOp**

(53)

PhO,

,OPh

oAo

PhH

____t

Ph

X

PhO, ,OPh o,/p\o

Ph4

3 (57)

The interaction of secondary alcohols with either triphenyl phosphate or diphenyl phosphorochloridate under conditions of thermolysis provides alkenes through effective d e h y d r a t i ~ n .Mixtures ~~ of dialkyl hydrogenphosphates and alkyl dihydrogenphosphates (generated from an alcohol and P4010) act as alkylating agents for alcohols and phenols.53 Mixed phosphoric-carboxylic anhydrides are obtainable from carboxylic anhydrides and trimethylsilylphosphorus(V) esters." Study of the photolytic behaviour of triaryl phosphates has been further extended; new model substrates examined include tri-I-naphthalenyl, tri-9anthracenyl, and tri-8-quinolinyl phosphates, together with some of their methoxy derivatives and analogous dialkyl aryl and alkyl diary1 esters. Noted reactions include aryl migrations with the formation of, for example, 1-[2-(1naphthaleny1)-naphthalenyl] phosphate, in substantial amounts, together with appropriate b i a r y l ~A. ~preliminary ~ ~ ~ ~ report describes the photolysis of methyl alkenyl aryl phosphates (58) which undergo transformation along more than one pathway. The isolated products from (58) (R' = OMe, R2 = R3= Me) were (60),

Organophosphorus Chemktry

112

(61), and (62), in yields of 16%, 25%, and 14%, respectively. Other substrates in which R' = H or OMe and R2 = Me, R3 = H, or R2R3= (CH2)4, yielded only the corresponding (60) and (61).57 I-\

singlet

Me0

[ z;4 triplet

\

J

MeO-P

+

R3C-QR1H I II

0

Me0

R2

The replacement of chlorine by fluorine in a range of phosphoryl compounds is achievable by the action of Et3N.3HF or with other salts of HF5* or with KF in the presence of 18cr0wn-6.~~ The replacement of chlorine at phosphorus in a perhydro-l,3,2-oxazaphosphorine by PhNH using PhNHLi proceeds with inversion of configuration.60A 31PNMR spectroscopic study of phosphorylations using the phosphoryl chlorides (RO)2P(O)Cl (R = Me, Et, or Bn) in the presence of pyridine has demonstrated the formation of intermediate N-phosphoryl species, together with dealkylation products and pyrophosphoryl species.61 The diastereoselectivity of reaction between the bicyclic phosphorochloridate (63) and the nucleophiles PhCH2CH2X (X = OH, SH, or NH2) depends on the nature of the accompanying (tertiary amine) base. With the alcohol or thiol in the presence of DBN, the reaction proceeds with preferential retention of configuration at phosphorus, but with preferential inversion in the presence of DBU. On the other hand, irrespective of the accompanying base, the amine nucleophile reacts exclusively with inversion; with DBN, the main reaction product appeared to be (a), considered to be a true reaction intermediate.62 Partial, kinetic, resolution occurs during the reactions between the chloride (65) and chiral amines (67)-(69) to give the respective (66). The best resolution was achieved with amine (69) in a reaction at 0 0C.63 The question has been raised as to whether fluoride acts as a catalyst or inhibitor of phosphoryl transfer. It would appear that for certain substrates, e.g.

4: Quinquevalent Phosphorus Acirls

(65) 2 = CI (66) Z = NHR

113

(67)R'=Me, R 2 = H (68) R ' = Pr', R2=4-CI (69) R' t Pr', R2 = 2-Me0-5-Me

4-nitrophenyl phosphates or those based on the 8-hydroxy-N-methylquinolinium ion, the rates of hydrolysis are accelerated through the fast formation and destruction of intermediate (R0)2P(0)F. On the other hand, F- acts as a net rate inhibitor when protonation of the leaving group in autocatalysis O C C U T S . ~ Further demonstrations of the effectivenessof particular cations in phosphoryl transfer reactions include the reduced activity of LiF, in contrast to other fluorides, in nucleophilic catalysisa and the requirement for 'two' Mg2+ ions in the enzymic hydrolysis of phosphate monoesters by inositol monoph~sphatase.~~*~ The role of cations in the acid-catalysed hydrolysis of diethyl 2-pyridinyl phosphate and in the base-catalysed hydrolysis of the 8-(dimethoxyphosphinoyl)N-methylquinolinium system has been investigated. In both cases, the rates of hydrolysis depend on the nature of the cations in the buffer media, and the formation of substrate-cation complexes was ad~ocated.~' The uncatalysed hydrolysis of the 1,3,Zdioxaphosphorinane(70) is slower than that of the ester epimeric at phosphorus because of the generalized anomeric effect, but some antibody preparations are able to reverse this order.68

114

Organophosphorus Chemistry

H20

b

-02cM

o/' \0

! C 0 2 H

\ / (72)

/H20

0

C02H

0-7-0OH

OH

0-

Scheme 3

(73)X = H (74)

x = c02-

Full details have now appeared of two detailed studies concerned with the hydrolysis of bis(2-carboxyphenyl) phosphate(^).^^*^^ In the first study, semiempirical calculations on the conformer populations for structures in which one carboxy group is ionized and the other is not were made to determine the relative role of the ionized group as a nucleophile to the phosphate group, and the ability of the unionized group to hydrogen bond with the phosphate group, during the loss of one aryl group.The substrate (72) was obtained by the hydrolysis of the ester (71) (R = SiMe3), and its hydrolysis was then studied using 'H and "P NMR spectroscopy. The course of the hydrolysis is that indicated in Scheme 3.69 Other carefully designed substrates included (73) and (74), and the dicarboxylic acid (79, in which the cyclic nature of the molecules constrains the relative positions of phosphate and carboxy groups.70 Under neutral conditions (75) hydrolyses approximately lo8 times faster than (74) and lo8 - lo9 times faster than diphenyl phosphate. HPLC and "P NMR spectroscopic data, and also l 8 0 isotope effects on 31Pchemical shifts, show the existence of an intermediate cyclic acyl phosphate in the g,g conformation, and the incorporation of two "0 atoms into the ultimately freed phosphoric acid (Scheme 4).70

4: Quinquevalent Phosphorus Acidr

115

~]

1

\ / 2

ow -s

*-PYO

2H

\ /

\ /

Scheme 4

In boiling xylene, 0-aryl 0-methyl 0-2-propynyl phosphorothioates isomerize to 0-aryl 0-methyl S-propadienyl phosphorothioates, although with only low to moderate conversion^.^' The anions from the conventionally-synthesizedmonothiophosphate esters (76) (R' = H or Ph, R2 = H; R'R2 = (CH&, n = 3 or 4) rearrange, and on subsequent alkylation or acylation (R' = Me, Et, Pr, Pr', Ac, Bu'CO, (PhO)ZP(X), X = 0, S, or Se) yield the products (77) in the (2) config~ration;~~ the latter esters undergo Diels-Alder reactions with common dienophiles (e.g. acrylonitrile, acrolein, maleic anhydride, eic.) to give the systems (78).73The reactivity of 0,O-diisopropyl phosphorodithioic acid towards sulfurcontaining terminal alkynes has been examined under a variety of experimental conditions; reactions in MeCN solution without additives very often fail, and in other cases provide only poor to moderate yields of alkene adducts, and the best yields of the latter - mostly of the form (PfO),P(O)CH=CHR and as mixtures of ( E ) and (Z)isomers - are obtained by reactions which incorporate AIBN.74 The thermolysis of three phenylated phosphoric triamides has been studied by IR, MS, HPLC, GClMS and DTA-TG/DTG technique^.^^ Diethyl phosphoramidate reacts with acetals of aromatic aldehydes, but not with those of aliphatic aldehydes, to give N-phosphorylated i m i n e ~ . ~ ~ The phosphorothioic triamide (79) (R = H) exhibits ambident reactivity and when alkylated yields the pentacoordinated S-derivatives (80), but when acylated affords (79) (R = PhCO or EtC0).77 The N to 0 rearrangement of the Nphosphorylated amino acid esters (81) to (82) proceeds 10-40 times faster in the presence of imidazole than in its absence. In a warm alcohol solution ester

116

Organophosphorus Chemistry

exchange precedes migration, but at higher temperatures, migration occurs so rapidly as to become the predominant process.78 O-Phosphorylated hydroxyamino acids have been prepared el~ewhere.’~

In the expected conversion of (83) into (84) by the action of aniline in the presence of DABCO, the products actually isolated were (85) and (86).80 Ester-amides of type (87) may theoretically react with nucleophiles at either C=O or P=O, and to decide the actual point of attack, the reaction@)between (87) and 4-methoxyaniline have been re-examined following earlier studies which

4: Quinquevalent Phosphorus A c i h

117

0

0

II PhO-P-N(CH&H2CI)2

A

I

wN-Ph I

PhO-P-N

I

X

i;’

II

NHPh

Ph

(83) X = CI (84) X=NHPh

suggested that the products were (88) and (93). The new study has now shown a complete lack of reactivity between these two substances under anhydrous conditions; in the presence of moisture, however, the acids (89) and (94), were both isolated as their arylamine salts. The earlier work also suggested that the methanolysis of (90) initially gave (99, although the latter was not detected, and the final products were N,N’-dimethyloxamide and dimethyl methylphosphoramidate; this result has now been confirmed, with the isolation of (95) and the demonstration that further methanolysis affords the products originally found. The importance of the nature of substituent at phosphorus, as well as that of the attacking nucleophile, was also demonstrated. Thus, (91) is inert to neutral methanolysis, whereas methanolysis of (90) and (92) occurs through attack at P=O to give, respectively, (95) (isolable under controlled conditions) and (96). In the presence of triethylamine (i.e. basic conditions), however, the products from (91) include (99) and (100) implying initial attack at P=O followed by that at G O . Methanolysis of (87) initially affords (97) by attack at P=O, followed by a cyclization step with loss of PhOH (i.e. again attack at P=O), ring opening involving attack at P=O to give (98), and subsequent liberation of MeOC0.CO.NHMe through attack at C=O.** Me

R,

X ’

o” P\ NMeCOCONHMe Me

(87) R=OPh (88) (89) (90) (91) (92)

R = NHCeH40Me-4 R = OH R-NHMe R = NMe2 R=NH2

f

Me2N, /O-

MeNEt3

’P\ 0’ NMeCOCONHMe (99)

(93) R = OPh, X = NHCGH40Me-4 (94) R=OPh, X = O H (95) R=NHMe, X=OMe (96)R = NH2, X = OMe (97) H = OPh, X = OMe (98) R = X = O M e

118

Organophosphorus Chemistry

0.0-Dialkyl N,N-dialkylphosphoramidothioates react with POC13 to give the products RSP(O)(NR'2)Cl, with the exception of the 0,O-diethyl N, N-dimethyl substrate which furnishes a complex mixture of products including PSC13 (9.5%), (Et0)2P(O)C1 (42%), Me2NP(0)C12 (15%), (EtO),PS (3%), EtS(Me,N)P(O)Cl (3%), and EtS(EtO)P(O)Cl(2%). Ethyl metathiophosphate, [EtOP(=O)(=S)], has been generated by the thermolysis of 0-ethyl N-substituted phosphoramidothioates, and its chemistry studied.84* 82983

3

Phosphonic and Phosphinic Acids

The year's activities have been slightly unusual in that almost all reported efforts, other than those in relation to structural studies, have been directed towards synthesis. A series of articles has reviewed the properties of hydrogenphosphonates.85Developments, during the last two to three decades, in the synthesiss6 and reactivitys7 of derivatives of phosphonic and phosphinic acids, have been summarized and discussed. 3.1 Synthesis of Phosphonic and Phosphinic Acids and their Derivatives 3.1.1 Phosphonic and Phosphinic Halides. - The interaction of PCls with methylenecyclobutane, with subsequent decomposition of the initially formed quaternary phosphonium salt, yields the phosphonic dichloride (101);88in the same way, P-pinene gives a mixture of (102) and the ( E ) and (2) forms of (103).89 The chlorophosphonation (PC13, 0 2 ) of ally1 chloride yields a mixture of phosphonic and phosphoric dichlorides containing 72% of separable [bis(chloromethyl)methyl]phosphonic 3-Substituted-adamantols are dichlorophosphonoylated, with high yields, by the use of PC13 in trifluoroacetic acid, sometimes containing 0.5 equiv. trifluoromethanesulfonic acid, with replacement of the OH group,9*and other phosphorus(II1) chlorides in sulfuric acid have given esters of 1-adamantylphosphonochloridicacid.92 Further reports have appeared on the preparation of tert-butylphosphonochloridi~~~~~~ and -bromidi^^^ acids by the hydrolysis of their trimethylsilylesters.

3.1.2 Alkyl, Cycloalkyl, Aralkyl and Related Acids. - Reports on MichaelisArbuzov reactions continue to be widely distributed throughout the literature. Phosphite-phosphonate isomerization occurs in the presence of copper@)

4: Quinquevalent Phosphorus A c i h

119

halides.” A variety of (chloromethyl- or bromomethyl-furany1)methyl halides undergo normal Arbuzov reactions with trimethyl p h ~ s p h i t e .2~ ~and 3mono(bromomethy1)-, and 2,3-bis- and 2,5-bis(bromomethyl)-furancarboxylates also react normally with the same phosphite, but dehalogenation may predominate when other groups, e.g. AcOCH2, are also present.97 In Michaelis-Becker reactions between 2- or 3-(chloromethy1)furans and NaOP(OMe)2 in MeOH both the methoxymethyl derivatives and phosphonic diesters are produced, the latter in smaller proportions. Sodium tert-butoxide affords even poorer yields of phosphonate esters but also less of the ethers.97 A detailed study of reactions between dialkyl phosphite anions and nitrobenzyl bromides has been described.98 In reactions between the halides and the phosphites (RO)*PONa in a solvent (THF, PGOH, or MeOD) the observed products (Z = 2-, 3-, or 4-nitro), apart from phosphonic diester (104), are those of reduction, (105) or (106), coupling (107), and ether formation (108). Phosphonate formation was moderate for Z = 2-nitro (R = Me), rather higher (5 1-97% isolated yields) for Z = 3-nitro (R = Me or Pri), but extremely low for Z = 4-nitro (R = Me) and absent for R = Pr’. In all cases when R = Me, ether formation also occurred. In cases where the yields of phosphonate were low, the yields of (107) were correspondingly high, and vice versa. Reactions performed in darkness, daylight or W, produced little variation in the yields of phosphonate ester (R = Me) for Z = 3-nh-0, but for Z = 2-nitro- or 4-nitro-, no diisopropyl phosphonates were obtained under various conditions. Probable mechanisms of reaction were

More complex phosphinic derivatives e.g. (109) [R’ = CH2CH(CH2CH2Ph)

COOR (R = Bn or But), R3 = simple alkyl or functionalized alkyl] have been prepared by the alkylation of the corresponding species (1 Other examples will be encountered in later sections, in particular Section 3.1.9. The electrolysis of diisopropyl (1-chloro-1-cycloalkyl)phosphonatesin MeOH and using a carbon cathode and magnesium anode, results in dehalogenation to esters of the cycloalkylphosphonicacid. loo

3.1.3 Alkenyl, Alkynyl, Aryl, Heteroaryl and Related AcidlF. - l-Alkenyl- or 2alkenyl-phosphonic diethyl esters have been prepared in good yields through Claisen rearrangements (Scheme 5 ) (R = Me or EtO).lol Silylation of diethyl

120

Organophosphorus Chemistry

Scheme 5

w P03Et2

RMe2Si

(1ithiopropenyl)phosphonate yields the 3-silyl-1-alkenes (1 11) (R = Me or But) which, under the influence of (the) LDA, provides a mixture of (1 12) and (1 13) as by-products in the formation of (1 11).lo2Syn-elimination occurs within the initial adducts (1 14) from diethyl (2-oxoalkyl)phosphonates and sodium dialkyl phosphites to provide dialkyl (2-phenyl-1-alkenyl)phosphonates.lo3 Correct conditions for clean reactions between the acetals (115) (R'= H or Me; R' = H, Me, or Ph) and (Me0)3P-PC13to give the phosphonates (117) via (116) require the reactants to be in the ratio 3:2:1.lO4 A reaction between diethyl(lithiomethy1)phosphonate and (1 18) is reported to give the ester (1 19) in high yield.loS

R'

'Ph

4: Quinquevalent Phosphorus A c i h

121

(115) X = OMe (116) X - C I

(E,E)-( 1,3-Dienyl)phosphonates have been obtained through the coupling of diethyl ethenylphosphonate and enol triflate ethers in the presence of Pd(0Ach in DMF containing a base such as K2C03-KOAc or Bt13N.l~The corresponding (E,Z)-isomers were obtained from diethyl (2)-(2-iodo- 1-ethenyl)phosphonate and the functionalized alkenes H2C=CHR (R = CHO, COOMe, COMe, or Ph) in the presence of P ~ ( O A C ) ~ - P ~ ~ P -inAMeCN,lo7 ~ ~ C O ~ and a similar coupling with a l-alkyne yields the (1-ene-3-yne)phosphonicester.Io7 The (E,E)-dienylphosphonates (121) result when the esters (120) are treated with Pd(dibenzy1idenea~etone)~.MeCl-PPr'~ at a little above room temperature,lo8 (or simply with Bu3P109)but at higher temperatures, the isomeric (E,E)-dienes (122) are formed. lo*

One route to (l-alkyny1)phosphonic esters depends on the base-catalysed destruction of enol phosphates (123) obtained in situ from (2-oxoalky1)phosphonates; in the case of (123) (R = Et), a mixture of (l-butyny1)- and (2-butyny1)phosphonic esters was obtained, but in all other quoted cases only the acetylenic compound was obtained. lo A second route starts with diethyl (trichloromethy1)phosphonate (a reagent of increasing synthetic importance)followed by sequential reaction in one-pot with BuLi (two equivalents), an aldehyde (RCHO), and a lithiumdialkylamide, and gives the products (EtO),P(O)C = CR in very high yields. 0

0

11

11

(EtO)*PCH&R

-

NaH-THF

(Et0)2P(O)CI

0 BU~OK _____t

II

(Et0)zPCGCR

Organophosphorus Chemistry

122

Reactions between diethyl hydrogenphosphonate and ArX (X = I or Br) to give diethyl arylphosphonates have been carried out in the presence of a phase transfer catalyst. l 2 Bis(trimethylsily1) phenylphosphonite reacts with alkyl halides to give [(ar)alkylphenyl]phosphinic derivatives, and it also adds to a$unsaturated carboxylic esters (as well as to nitriles and amides) to give (2functionalized-1-alkyl)phosphinic derivatives. l3 X-Ar-NH2 (124)

Nu(1)

Nu(l)--Ar-NH2

-

Nu(1)-Ar-X

(125)

Nu(2)_

Nu(l)-Ar-N~(2)

(126)

Scheme 6

Many reactions leading to heterosubstituted-arylphosphonic diesters have been described which fall within the general Scheme 6 of sequential photostimulated SRNl processes, where Ar is a benzene, naphthalene, or pyridine nucleus. Starting with the substituted (2-, 3-, and 4-) arylamine (124) [x = I, Br or (EtO)zP(O)], in reaction with KOP(OEt), [Nu(l)], and replacement of the amino group in (125) by a second replaceable group by classical methods, allows a second SRNl reaction to be then carried out on (126) with ArSH, KOP(OEt),, C5&NSH, C4H3N2SH1etc. [Nu(2)]. l4 Relatively few syntheses of (heteroary1)phosphonicderivatives have been noted during the year. The C-phosphorylated imidazoles (127) (R = alkyl or aryl) were obtained from diethyl (cyanomethy1)phosphonate'l5 and (2-hydroxy-5-thiazoly1)and [3-hydroxy-5-(1,2,4-triazolyl)]-phosphonic diesters were obtained by the lithiation of the corresponding 2- and 3-methoxy systems, followed by phosphorylation with (Et0)2P(0)C1, and subsequent demethylation of the products with aqueous HC1 or HBr. l 6

The benzoselenophene phosphonic acid (128) has been obtained from phenylethynylphosphonic acid and Se02-HBr'l 7 and classical reactions were employed in the synthesis of the pyridone acids (129) (R' = aryl or heteroaryl, R2 = H or COOMe).ll* 3.1.4 Halogenoalkyl and Related Acids. - The synthesis of (2-chloroethy1)phosphonic acid has been reviewed.' l9 Michaelis-ArbuzovlZ0and Michaelis-Becker121 reactions continue to be employed in the synthesis of polyhalogenated-alkyl

4: Quinquevalent Phosphorus Acids

123

(particularly 1,l-difluoroalkyl)phosphonic diesters. The formation and use in situ of cadmium compounds from dialkyl (polyhalomethy1)phosphonates is well established.120*122 Also noted has been the addition of diethyl (difluoroiodomethy1)phosphonate to alkynes to give (E)/(Z) mixtures (of composition 1OO:O to 5O:SO) of the phosphonates (13O)l2O and that of the radicals derived from (R0)2P(X)H (X = 0 or S) to the 1,l-difluoroalkenes, R1R2C=CF2to give the products (131).123J24 X

0 I1

(Et0)2PCF2CH=CIR

II

( R0)2PCF2CHR1R2

(131 1

(130)

The replacement of OH on carbon adjacent to phosphorus by Br or I using ally1 bromide or Me1 in the presence of carbonyldiimidazole, has been reported.125 The electrolysis of diisopropyl (trichloromethy1)phosphonate in DMF containing the alkyl halide RX with a carbon cathode and magnesium anode affords diisopropyl (1,l -dichloroalkyl)phosphonates (1 32); interestingly, the corresponding diethyl esters may be reduced further. 126 A similar reaction leading to (1-chloro-1cyc1oalkyl)phosphonicdiesters (133) has already been referred to.'O0 0

I1 (Pri0)2PCC12R

e-; RX-DMF

m- y

II

(132)

\

-

e-; Br(CH2), Br-DMF

II

n

(priO)2~-wH2), CI

A new route to (a,a,-difluorobenzy1)phosphonicesters which does not use the DAST reagent, employs 4,4-dimethoxy-2,5-cyclohexadienoneand its reaction with diethyl (lithiodifluoromethy1)-phosphonate (Scheme 7).127 Syntheses of further halogen-containing and additionally functionalized phosphonic diesters will be referred to in several of the following sections. 3.1.5 Hydroxyalkyl and Epoxyalkyl A c i h . - The reaction most widely adopted

for the preparation of (1-hydroxyalkyl)phosphonic esters is that attributed to Abramov and involves the interaction of hydrogenphosphonateswith aldehydes or ketones, sometimes in the presence of a base catalyst. The same reaction has now been shown to be catalysed by mineral phosphates e.g. fluoroapatite.lZ8The same process, catalysed by the complex (134)[(R)-form] gives the same esters in SO-95% yields and with 5590% e . e . ~ ~The * ~ study of the diastereoselective phosphonoylation of aldehydes using chiral 1,3,2-diazaphospholidine reagents has continued with an examination of the use of the stereoisomers of (139, which

124

Organophosphorus Chemistry

; ii, HCI, Me2CO; iii, NaBH4, CeC13-7H20, MeOH; iv, BnOC(=NH)CC13, TfOH, C6HI2, CH2C12; v, H2, 10% Pd-C, EtOH.

Me0 OMe

Scheme 7

display a pattern of selectivities different from those previously reported for reagents such as (136).130Compound (137) has been recommended for a 31PNMR spectroscopic assay of enantiopurity of (1 -hydroxyalkyl)phosphonic esters; diastereoisomeric 0-derivatives exhibit chemical shift dispersions of up to 5 ppm.131

CH~BU'

The use of silyl phosphite esters in the Abramov reaction is well established, but a practical modification involves the addition of Me3SiCl to a mixture of triethyl phosphite and carbonyl reactant at room temperature.132The addition of a silyl phosphite (R2 = Si-containing group) to a chiral hydroxyaldehyde derivative (138) (R' is also a Si-containing group) affords a mixture of the diprotected diastereoisomeric (1,2-dihydroxyalkyl)phosphonicesters (1 39) and

125

4: Quinquevalent Phosphorus Acids

(140); the best yield (67Y0)and diastereoisomeric ratio (synlanti 92:8) was obtained using the bulk of R' = Pr'3Si for R = Me and R2 = Using this methodology, trimethylsilyl dibenzyl phosphite and 2-(triisopropylsilyloxy)propanal (protected (S)-lactaldehyde)have provided diastereoisomeric dibenzyl ester analogues of (139) and (140) (R = Me; R' = Pr'& R2 = Me&), the first of which was transformed into (1R,2S)-(-)-( 1,2-epoxypropyl)phosphonicacid (fosfonomycin).134

It might, at this stage, be noted that regioselective silylation of diethyl [2-(4methoxypheny1)-1,2-dihydroxyethyl]phosphonateoccurs at the 2-OH group, with greatest regioselectivity being achieved with ButMe2SiC1 with trimethylpyridine or pyridine itself in DMF, but regioselectivity is not necessarily as great when the 4-methoxyphenyl group is replaced by alkyl.135 The enantioselective reduction of diethyl (2-oxoalkyl)phosphonateswith Succharomyces cerevisiue can be achieved with good results; up to 100% e.e.s were obtained in some cases.136In a series of examples, reductions of the esters (141) (X = mono- or di-halogen, Me, MeO, NOz, MeS, or MeSO2) by the boranes (142) were carried out in the presence of (S)-(143). Moderate to good enantioselectivities were found (with up to 80% e.e.) with (142a)-(143b), but the use of the catechol borane (142c) gave both high chemical yields and excellent enantioselectivities. The procedure was applied to reductions of the carbonyl group in 1-, 2-, and 3-oxoalkyl phosphonates.137 The combination of reagents (142c) and (143b) was favoured by other workers

(b) R = Et (c) R = Pr'

(d) R = Bu'

(143) (a) R = Me (b) R = BU (c) R = Ph

Racemic (1-acetyloxyalkyl)phosphonic diesters may be enantioselectively hydrolysed in biphasic systems containing a lipase from Aspergillus niger, although selectivity is reduced if the alkyl chain in the substrate is branched. The resultant acids and esters (largely of opposite chirality) are separable, and the unreacted esters may then be saponified separately. Two experimentally useful features worth noting are the greater ease of hydrolysis of 0-chloroacetate esters relative

126

Organophosphorus Chemistry

to the and, of the phosphonate ester groups, dimethyl esters are the most easily hydrolysed.140The presence of a 2-substituent in the parent (hydroxyarylmethy1)phosphonic diester reduces the hydrolysis rate by lipases from AspergiZZus niger and Rhizopus oryzae. 140 (3-[ 1-(Acyloxy)alkyl]- phosphonates are enzymically hydrolysed more easily than their (R) enantiomers.140 Elsewhere, a lipase enzyme was also used successfully in the resolution of racemic ( l a ) , as its acetate ester.14* Acetyloxylation in (145) in the presence of a palladium catalyst occurs at the y-position to give (146) (R1R' = H, Me, or Ph) .142

0

0 Pd(OAc)2 b

MnOp, benzoquinone HOAc

Lithiated diethyl allylphosphonate reacts with ketones under either kineticallycontrolled or thennodynamically-controlled conditions. Under the former conditions, reactions which involve acyclic or cyclic ketones at -78°C afford the compounds (147); acetophenone yields a mixture of the corresponding (147) together with (148), but benzophenone yields only (148). In all cases, the yields tend to be low. Under thermodynamic conditions (addition at -78 "C and the mixture allowed to come to room temperature) further reactions become possible; acetophenone then yields (148) together with (149), and other ketones capable of enolization generate the enol lithium salt together with diethyl (1-propenyl)phosphonate which interact further to give (149). Thus, acetone yields (148) and (149), whereas cyclopentanone and cyclohexanone each yield the corresponding (147) and (149); yields are again P03Et2 ,

I

Li+

i, R'R2C0 ii, NH4CIaq. *

P03Et2 X

O R2

I

R' CH2COR2

H

R'

cp0 R2

4: Quinquevalent Phosphorus Acids

127

The opening of appropriate epoxide rings by a dialkyl (1ithiomethyl)phosphonate is the initial step in syntheses of several biochemically-interesting hydroxy phosphonic derivatives, examples of which include phosphonomethyl analogues of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, 144 a phosphonate isostere of 2-deoxyribose-3-phosphate, 145 and the compound (150) (B is a nucleoside base).146(1,2-Dihydroxyethane)-1,l -bisphosphonic acid (1 52) has been synthesized through the ring opening of tetrasodium 2,2-oxiranebisphosphonic acid (151).14' The treatment of epoxides or glycidyl derivatives with tris(trimethylsily1)phosphite can result in extensive deoxygenation, amounting to 98% in the case of styrene epoxide; a reaction between the same phosphite and glycidyl mesylate at 130 "C is more complex and yields both the lactone (153) and the 2-mesylate (154) of (2,3-dihydroxypropyl)phosphonic acid as well as phosphoric and methanesulfonic acids, but no organophosphorus products were characterized when the corresponding 3-nitrobenzenesulfonatewas employed.148

Br2-H20

H&=C(P03Nah

HOCH2CBr(POsNa2)2

NaOH aq. r.t.

r-? H0-r I

ij (153)

(154)

(155) X = O H (156) X = H

The reactions which take place between acetophenone and PC13 have been revisited.149Reactions between diethyl hydrogenphosphonate, (Me3S&NM (M = Li, K, or Na), and an acyl chloride RCOCl in the ratio 2:2:1 in THF at - 100 "C during periods of only seconds lead to only (155) (R = alkyl) or to mixtures of (155) and (156)(R = But or Ph).150 Compounds of type (155) (R = n-C2-Cloalkyl group) are also obtained from alkanoic acids and PC13-H3PO3mixtures.151 The treatment of (157) (R = Ac, R' = Bn) with (Me0)3P-trimethylsilyl trifluoromethanesulfonate, gives a high yield of the mixture of anorners of (158) (R'= Bn) in the ratio 1:1.7 (a$).This ratio is reversed when R = R' = A c . ' ~ ~

128

Organophosphorus Chemistry

(157) X = O R (158) X = P03Me2

Reactions between bis(trimethylsily1) phosphonite and diketones have been reviewed in several earlier Reports; the products are derivatives of phosphinic acids. A new study has examined the reactions between the same reagent and 1,4diketones.153 The nature of the products was determined after hydrolytic removal of trimethylsilyl groups and methylation (diazomethane) of all acid OH groups. The reactions of relevance to the present section are: (i) the formation of derivatives of 1,4dihydroxybutane-1,4-diphosphinic acid, as exemplified by the conversions of (159a-c) into the corresponding (160), (ii) the conversion of the analogous (159d,e) into the corresponding (161) as examples of the formation of derivatives of (4-hydroxybuty1)phosphinic acid. (iii) the formation of 5-hydroxytetrahydrofuranyl-2-phosphinicacids, as exemplified by the conversion of (162) (R = 4-methoxyphenyl) into (163), and (iv) the formation of phospholane derivatives, exemplified by that of (164). Several steps are involved in each of the three sequences. Bearing in mind that phosphinic acids can be oxidized to phosphonic acids, the potential for the preparation of many novel phosphonic acids is high.153

.'WR2

OMe 0 1

WR2 ((342)"

0

H'g'OMe

(159)(a) R1 + R2 = (CH2)3, n = 1 (b) R' + R2 = (CH2)4, n = 2 (c) R' = H, R2 = Ph, I/ = 2

(160) OMe

(159)(d) R'= H, R2 = Me, n = 1 (e) R' + R2 = (CH2)4, n = 1

I

-

H-P=O %R2 0

R' (161)

0

Ph

129

4: Quinquevalent Phosphorur Acidr

(165) R = CH20S02CF3 (166) R=CHO

Reagents: i, 2BuLi, Me3SiCI, THF; ii, (165); iii, a, LiOEt, b, NH&I aq. ; iv, Me3SiBr

Scheme 8

Two routes have been explored for the preparation of fluorine-containing phosphonic analogues of glycerol-3-phosphate.In the first (Scheme 8), a straightforward reaction between a fluorine-containing lithiated carbanion and (165) ultimately leads to the monofluoro derivative (167). In the second route (Scheme 9), diethyl [difluoro(trimethylsilyl)methyl]phosphonate (168) is made to react with (166) and the OH group in the resultant (169) is then removed by a standard procedure; finally, the product (170) is de-esterified, again by standard means, to give the acid (171).154J55

0

II

(Me3Si)F2CP(OEt)2

-

(170)

R (169) R = O H (170) R = H

Scheme 9

For further mention of (1-hydroxyalkyl)phosphonates in the context of the Kabachnik-Fields reaction, see Section 3.1.9.

130

Organophosphorus Chemistry

-

0

0

II

II

(R0)2PCH2COOR

H30'

(R0)2PCHCOOR

I

0

II

(R0)2PCH2COR1

0

II

(H0)2CHCF2P(OEt), (175)

3.1.6 Oxualkyl Acids. - Phosphonoacetic esters form the starting point for widely reported acylation procedures for the preparation of (2-oxoalky1)phosphonates. Treatment of the phosphonoacetic ester (172) with Mg(OEt)2156or MgC12-Et3N157p158 followed by R'COC1, and acidolysis of the products (173) yields the desired oxoalkyl phosphonic esters (174). The same or similar products are obtainable from l-(dialkoxyphosphinoy1)carboxylic chlorides when alkylated or arylated with organocopper or organomagnesium reagents. 59 When acylated with carboxylic esters, diethyl (1ithiodifluoromethyl)phosphonate yields diethyl (1,l -difluoro-2-oxoalkyl)phosphonates.1~ On reaction with DMF, the same (1ithiodifluoromethyl)phosphonate affords the carbonyl-hydrated compound (175). 160~161Acylation of the carbanions from the (aminomethy1)phosphonates (176) with oxalic acid derivatives provides the (1-amino-2-oxo)alkyl compounds (177) (Z = Pr'O or Et2N; R'R2 = Et2N or (CH2)n, n = 4-6); the latter exist as mixtures. Also, mixtures of keto and enol tautomers, the latter as ( E ) plus (2) carbanions from non-functionalized alkylphosphonic esters react with the reagent (178) to give (179) which may be hydrolysed to the (2,3-dioxoalkyl)phosphonates (180).162 0

0

It

II

(Et0)2PCH2NR'R2

(Et0)2PCHNR1R2

EtOOCC(OR')2R2

I

;if/ (Et0)2PCHRCCR2(0R1)2 (179)

0

II

00

II I I

(Et0)2PCHRC.CR2

(180)

Esters of (trichloromethy1)phosphonic acid form good starting points for the preparation, albeit through several stages (Scheme lo), of the (1-formylalkyl)phosphonates (18 1).163 The formylation (using ethyl formate) of carbanions The from (2-alkeny1)phosphonic esters is regiospecific at the a-position. carbonyl-protected a-phosphinoylated propenals (182) (R = H or Ph) have been noted. 65

4: Quinquevalent Phosphorus Acicis

131

0

II

0

(R' 0)2PCCI3

oII

iJ-

(R'O)pPCLiCI(SiMes) 0

II

II

T]

(R'0)2PCHR2CH0

(1811

ii

(R'0)2PCR2CI(SiMe3) 0

I1

0

(

p+0)2

1.

H

II

(182)

(R'0)2PCR2=CH(OEt)

Reagents: i, 2BuLi, Me3SiCI,THF; ii, R2X, THF; iii, BuLi, THF; iv, HCOzEt, THF; v, HCI, CH2C12

Scheme 10

Reactions between carbonyl compounds and carbanions from the phosphonates (1 83) give, as has been seen already, the hydroxy phosphonates (184); in situ treatment of these as indicated (Scheme 11) proceeds through several stages via tetrahydrofuran intermediates to give, ultimately, the oxoalkenyl phosphonates (185); high yields of products were reported.166

(1 85)

Reagents: i, BuLi, THF; ii, R3COR4;iii, i2, NaHC03,THF aq.; iv, KOBU'

Scheme 11

Finally, the acid (186) has been isolated as the (E) and (Z)forms of the methyl carboxylates, characterized crystallographically as their dicyclohexylammonium salts. The two compounds exhibit markedly different reactivities. Thus, the (E) form requires prolonged treatment with alkali for its conversion into the tetrasodium salt which at pH 6-7then yields phosphoric acid; the (2) form reacts rapidly with alkali to give the tetrasodium salt, and this at pH 6-7 yields H203P.CN. 16* 679

N-OH II

H203P-C-COOH

Ph,

p

R 0 ' p ~ N 0 2

Ar (187)

0

II

(Et0)2PCF&HRCH2N02

132

Organophosphorus Chemistry 0

OH

EtOOC-

\

CF2P03Et2

Reagents: i, MeN02, KF, Me2CHOH;ii, MeS02CI, EtSN, CH2C12; iii, Ph@SCH2P03Et2, LiBr, Et3N, THF; iv, Et02CCH2P03Et2,LiBr, Et3N, THF

Scheme 12

3.1.7 Nitroalkyl Acidr. - Additions of hydrogenphosphinic esters, Ph(RO)P(O)H,169 or diethyl (lithiodifluoromethyl)phosphonate170to nitrostyrene or other nitroalkenes yield the nitroalkyl phosphonates (187) and (188), respectively. Diethyl (1ithiodifluoromethyl)phosphonate also, by reaction with DMF, has provided (175), as already noted; the condensation between the latter and nitromethane has given a 69% yield of (189);160 further reactions involving (175) (Scheme 12)161 have provided several additionally functionalized esters, amongst them (190). The addition of the carbanion from diethyl (3-buteny1)phosphonate to 1nitroalkenes yields the stereoisomericcompounds (191).171

3.1.8 Diazoalkyl and Azidoalkyl Acidr. - A convenient synthesis of dirnethyl (diazomethy1)phosphonate involves the initial interaction of dimethyl (lithiomethy1)phosphonate and 2,2,2-trifluoroethyl trifluoroacetate, followed by further reaction with an arylsulfonyl The compounds (192) (R’,R2 = dialkyl or

4: Quinquevalent Phosphorus Acidr

133

cycloalkyl) were reported during work on the synthesis of C-phosphorylated lac tarn^'^^ and (2-hydroxyalkyl)phosphonates have been converted into (2azidoa1kyl)phosphonates(using Ph3P-DEAD-NH3) en route to the 2-aminoalkyl compounds.*74 3.1.9 Aminoalkyl and Related Acidr. - Diethyl (l-aminoalky1)phosphonates have been prepared by reduction of the oximes of (1-oxoalkyl)phosphonates with N a B h in the presence of NiC12 or M00317sand diethyl (2-amino-2-arylethy1)phosphonates by hydrogenation of the methyl ethers or acetates of the oximes of the corresponding 2-0x0 esters. 176 The addition of hydrogenphosphonates or related compounds to imines or their trimers continues to be a widely employed p r ~ c e d u r e . ' ~Noteable ~ - l ~ ~ is the observation that whereas the addition of hydrogenphosphonates to (193) require a period of heating at 90°C for appreciable reaction to occur, sonication of reaction mixtures produces immediate addition to form (194).178Interest has tended to be centred around the potential for stereochemical control of the addition through modification to the stereochemistry of the hydrogenphosphonate or other phosphorus intermediate, or in the use of selected imines. Slight control was observed in the addition of (2S,4R)-(195) to (196); the products, (197), exhibited diastereoisomeric ratios of 40-4560-55.18* Modest diastereoselectivity was also observed in reactions between (198) and (199) leading to (200). 181 NHMe

CPh

I

Ph

R'

Organophosphorus Chemistry

134

The addition of lithium diethyl phosphite to the imines (201) from (R)-(-)-1amino-1-phenyl-2-methoxyethane gave mixtures of (202) and (203) in the ratios of >110:1 to 7:1, but mostly around 5O:l. The sequence was completed by hydrogenolytic removal of the benzylic group, when the product (1-aminoalkyl)phosphonic diesters had e.e.s of 96-99%.'82 The diastereoisomeric ratios within (205), obtained from the chiral sulfoxides (204) and diethyl (1ithiomethyl)phosphonate, varied from 4.9:l (R' = PhCH=CH) to 9.2:l (R' = 2-thienyl), but the ratio also depended, to some extent, on the nature of the phosphonate alkyl group.183

H

In the Kabachnik-Fields system, two nucleophiles, namely hydrogenphosphonate and amine, compete for the electrophilic carbonyl component, with the resultant formation of a (1-hydroxyalkyl)phosphonate alongside the target (1aminoalky1)phosphonate. From a study which employed potassium diethyl phosphite, butylamine, and a range of aldehydes and ketones, it is apparent that the 'softer' the carbonyl species, the faster the reaction with the 'softer' phosphorus nucleophile, and the slower the reaction with the 'harder' arnine.la In all those cases examined, the hydroxyalkyl phosphonates from aliphatic and aromatic aldehydes, and aliphatic ketones, decompose to carbonyl and phosphite reactants in the presence of the amine. In the case of the aryl carbonyl components, the system is further complicated by the rearrangement of (1hydroxyalky1)phosphonate to phosphate. In further cases when the carbonyl reactant is benzophenone or fluorenone, still greater complexity is observed, since phosphate formation is then also reversible.lS5 The interaction of racemic 1,2cyclohexanediamine with formaldehyde and potassium diethyl phosphite in the ratio 1:3:2 yields (206) and not (2O7).ls6 The condensation of (208) with a primary amine followed by the immediate addition of dimethyl hydrogenphosphonate yields the unexpected monomethyl ester (209), together with (210) as a by-product.18' In a one-pot procedure, diethyl hydrogenphosphonate, an aldehyde (selected aromatic or cyclohexyl) and a (15')-(+)-camphorsulfonamidederived carbamate (211) (R = cyclohexyl or isopropyl) yielded products with high diastereoisomeric excesses, and which on acidic hydrolysis furnished the (3-( 1aminoalky1)phosphonicacid. ls8

4: Quinquevalent Phosphorus Aciak

135

NHR

The list of reactions between hydrogenphosphonates, carbamates or amines, and aldehydes now includes those involving heterocyclic aldehydes. 89 Such methods can generally be adapted for the preparation of analogous hydrogenphosphinic acids by the use of bis(trimethylsily1) phosphonite or H $ Q . 179*190~191 A similar reaction between benzylcarbamate, 4-phthalimidobutanal, and Pel3 in acetic acid is reported to have yielded (1,4-diaminobutyl)phosphonic acid; the corresponding phosphinic acid was prepared from the same aldehyde and the hypophosphorous acid salt of diphenylmethylamine. 92

Ph

bh

R

In planning a general enantioselective route to (1-aminoalkyl)phosphonic acids, French workers originally considered the alkylation of (212)(R = H),but this procedure led to products of only moderate e.e.s. Newer work has now considered the preparation and use of the perhydro-l,4,2-oxazaphosphorine (213)(R = H).lg3The chosen synthesis started with (R)-(-)-phenylglycinol, and its N-benzyl derivative, when acted upon by formaldehyde, gave the oxazolidine (214)(R = H)in 95% yield; a reaction between the latter and trimethyl phosphite in the presence of SnCb gave the required product (213)(R = H)in 81% yield, as

136

Organophosphorus Chemistry

a mixture of two diastereoisomers in the proportions 4: 1. For each of these, the benzyl and phenyl substituents were assigned to equatorial sites, and the major isomer was assigned the equatorial P=O group. Unfortunately, conditions could not be found for the successful alkylation of (213) (R = H), and the synthesis sequence was therefore developed for other aldehydes, when four stereoisomers were obtained for R = Me or (CH2)3COOMe, and only two for R = Et, Pr, and Bn. NMR spectroscopic data suggested that the two major (or exclusive) compounds (always greater than 60% of total yield) were epimers at phosphorus, and it was concluded that the addition of trimethyl phosphite onto the chiral oxazolidine is a highly to totally diastereoselectiveprocess leading to the (major) (S) configuration at C-3. Hydrogenolysis to give the monomethyl (1 -aminoalkyl)phosphonates followed by acidic hydrolysis finally gave the free aminoalkyl phosphonic acids having the (S)-configurationwith e.e.s of 77-97%. Ig3 The amidation of a-hydroxyallylic phosphonates (215) with nitriles in the presence of trifluoromethanesulfonic acid proceeds with high (&‘)-stereoselectivity and with moderate to good yields of (216) [R2 = H, R3 = Me or Ph; R2 = Me, R3 = Ph; R2R3= (CH& n = 2-4; R4 = Me or Ph].” Mannich reactions between diethoxyphosphinoylacetic acid, a primary amine, and formaldehyde, have been used for the preparation of (217).195

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoaceticacid were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219).196A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-cbz protected (a-aminobenzy1)phosphonic acid.lg7 A synthesis of (aminomethy1ene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been notedlg8 and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%.199The pyrrolidine-based compound (222) has been prepared from methyl ( 3 - N methoxycarbonyl-4-oxo-2-pyrrolidinecarbo~ylat~~ and N-coupled 4-aminobutanal diethyl acetals were the starting materials in syntheses of the pyrrolidine2-phosphonic acid derivatives (223) in which 2 represents the N-protected amino acid or peptide moiety.201

4: Quinquevalent Phosphorus Acidr

137

0

It

&!(ON Ph)2

PhCH2CHP(OR)2

I

NHCOPh

I

C02Me

I

2

Three steps are needed for the conversion of (224) into (225) which, when acted upon by trimethyl phosphite, gives (226); the last may be alkylated (BuLi-RX) to give (227) as a cisltrans mixture. The compounds (228) are also obtainable from (224). The treatment of (228) with LiBb-LiBHEt3 yields (229) (R = H or Me). The geometries of trans-(227) (R = Bn) and (228) (R = allyl) were determined by X-ray diffraction.202Syntheses have been reported of 0-protected phosphohomoserine and its lactone203and, using well established reactions in a systematic way, the four diastereoisomers of phosphothreonine have been obtained from (230) and (231).2" The hydrogenation of racemic (232) in the presence of RuC12-(R)BINAP affords the stereoisomeric N-acetyl derivatives of phosphothreonine, and (233) (R = Ph) and (234) (R = Ph) were similarly obtained.205A further sequence leading to the same compounds commences with the asymmetric dihydroxylation of the appropriate (1-alkenyl)phosphonic ester followed by the replacement of one OH group through a cyclic sulfite.206Unsuccessful attempts, using enzymic hydrolysis of 0-acetyl derivatives, have been made to obtain all diastereoisomers of phosphonoisothreonine, synthesized as the N-protected derivatives (235) (R', R2 = Hcbz or phthalimido) from enantiomeric alaninal~.~~'

138

Organophosphorus Chemistry

(230)X = 0 (231)X = NSiMe3

(233)

NHAc

bH

(234)

(235)

Derivatives of phosphonoacetylaspartic acid (236) have been prepared. Thus, (237) with triethyl phosphite yielded (238) containing potentially easily removable ester groups, and similarly (239) afforded (240). Selective removal of the Me ester group, reduction and oxidation, with further hydrolysis, gave (241).208

(236)

(2411

(237) R' = Bn, R2 = But, X CI (238) R1 = Bn, R2 = But, X PO3Et2 (239) R' = But, R2 = Me,X = CI (240) R' = But, R2 = Me,X = P03Et2 I .

A standard reaction sequence was employed for the conversion of (242) into (244) via (243), and the last was converted, in turn, into (245). The reaction of the last with ammonium carbonate-KCN gave a stereoisomeric mixture of the spirans (246), the geometries of which were determined by NOE experiments, and hydrolysis and hydrogenolysis of which yielded (247) and the compound epimeric at c-4.*09 R'O,

:&O

P(OPr'), I

Cbz

(242) R' = SiMe2But,R2 = CO2Me (243) R' = SiMe2But,R2 = CH2P(0)(OPr'), (244) R' = H,R2 = CH2P(0)(OPri)2

Bn

(245)

4: Quinquevalent Phosphom Acicis

HNKNH

139

NH;

k

I Bn

The first recorded synthesis of the phosphonate analogue (251) of N-acetyl-aD-mannosamine 1-phosphate commences with the Arbuzov conversion of (248) into (249), and thence into (250) by aqueous trifluoroacetolysis. Standard reactions carried out on the last yield the target compound.210

BnOBnO *x

BnO& BnO P03Et2

(248) X = I, R = SiMe2But (249) X = P03Et2, R = SiMe2But (250) X = P03Et2, R = H

Preparation of the diazo compounds (192) has already been mentioned (Section 3.2.8); their treatment with rhodium acetate in an inert solvent yields either (252) or (253) depending on the nature of the various groups R. The products (252) are obtained when, in (192), R' = P? and R2 is P? or Bn, or when R1R2is (CH&.,, n = 4,5,or 6, or a group of effectively similar chain length. On the other hand, the formation of (253) was noted for very few exceptions. A particularly interesting case is that of (254) which yielded (255), from which (256) was readily obtainable.173 A synthesis of racemic fmoc-protected 4-phosphonomethylphenylalaninestarts with the Arbuzov preparation of (257) (R = Me or Bu'); standard modifications to the aryl methyl group lead to the desired (258).211Two procedures have been adopted for the preparation of the N-fmoc or N-boc derivatives of the difluoro derivative (259). In the first, triethyl phosphite and 4-(bromomethy1)benzoyl bromide and treatment of the resultant aroyl phosphonate with the DAST reagent yields (262); this reacts with the carbanion from (263) to give (264) hydrogenation of which (with PdC12) affords (260), then converted into its Nfmoc derivative and de-esterifiedwith Me3SiI.212In the second procedure, triethyl phosphite and 4-iodobenzoyl chloride, followed by DAST reagent, yielded diethyl [difluoro(4-iodophenyl)methyl]phosphonate which was caused to react

140

Organophosphorus Chemistry

( R’ 0 2 > ):N 2. 0

0

CQBu‘

0

(Bno)*yN$

-

0 C@R2

(255) R1 = Bn, R2 = But

(254)

(256)R’m R2 H P

with (265) to give (261) and this can be transformed into the fmoc derivative very quickly.213The addition of benzylamine to the phosphonates (266) yields (267) (R = Bn) hydrogenolysed to (267) (R = H).214 A reaction between a phosphonic diester carbanion and (268) yields the imines (269), reducible by cyanoborohydride to (270).*15

(257)

(258) R’ = R2 = H, X = H,2 = Fmoc (259)R’ = R2 = H, X = F, 2 = Fmoc or Boc (260) R’ = Et, R2 = H, X = F, Z = H (261) R1 = Et, R2 = Bn, X = F, Z = Boc

Ph

Through the use of bis(trimethylsily1) phosphonite with the appropriate coreactants, it is possible to construct intermediates, such as (271), useful in the synthesis of [(aminoalkyl)alkyl]phosphinic acids, not only by direct alkylation, but also by utilizing their hydrophosphonoylating ability (Scheme 13).216*217

4: Quinquevalent Phosphorus A c i h

141

fll N

P03Et2

K,,

Nkp03E

R1

F3C

F3C

R2

Scheme 13

Several communications, summarized in Scheme 14, have described the synthesis of many amino-substituted dialkylphosphinic acids and phosphonic acids, and also many similarly substituted hydrogenphosphinic acids. Alkylation of the phosphinates (272) (R' = H or Me, R2 = Et, R = H) yields the corresponding (273) which, in a single step, are convertible into the useful intermediates (274). With 1,2-unsaturated nitriles, for example, the (3-aminopropy1)phosphinic acids (275) may be obtained, reachable also through the alkylation of (275) (R = H). The phosphinic esters (274) also react with N-protected 3-aminopropanals to give (276). Yet a third sequence, providing isomers of (276), depends on the transformation of (274) into the phosphorus(II1) intermediates (277) in situ to be then converted into (279) via (278) and finally into the [(3-amino-2-hydroxypropyl)alkyl]-phosphinicacids (280), reachable also through the phthalimide derivatives (28 1) (ZNH = phthalimido).218-220 Further uses of hydrogenphosphinic esters include additions across carbon-to-carbon double bonds (cf. Scheme 13), illustrated by that of (282) in the preparation of (283), an intermediate in the synthesis of inhibitors of the D-glutamic acid-adding enzyme of peptidoglycan biosynthesis;221condensations with aldehydes or ketones to give [(aminoalkyl)(hydroxyalkyl)]phosphinic derivatives;220the formation of [(aminohydroxyalkyl)a1ky11phosphinic acids2 and other procedures.222 The conversion of (1-aminoalkyl)phosphinic acids into the corresponding (1 guanidinoalky1)phosphonic acids, e.g. (284), has been carried out as indicated, and the structures of (284) (R = Me, and R = Ph, monohydrate) have been confirmed by X-ray diffraction work.223 (Hydrazinoalky1)phosphonic esters were obtained from the corresponding (oxoa1kyl)phosphonic esters by the sequential action of hydrazine and a reducing *s2

142

Organophosphorus Chemiitry

0

EtO Rl

)

iii or iv I

EtO

0

~

-

2

c

(272) R - H (273) R = alkyl, aralkyl, 2cyanoethyl

v,vi,vii or viii

0 II H-P-R

(R3 = H)

I

OR2

R3

(274)

(275)

OH

[ biMe,] R,

p,~~2

0

H2NTi;R

x,xi (for x = CI) R-F, , - ) ,X xv,xi phthalirnido; (for X =

I

OR2

(278) (279) (280) (281)

(277)

0

X = CI _1xii X = NH2,R2= Et _1xiii X = NH2,R2 = H 2-E t x x i i i X = CGH~(CO)~N, R -

Reagents: i, NaH,THF,RX; ii, Na,EtOH, CH2-CHCN, HOAc; iii, for R' = H, (a) 4M HCI, (b) CIC02R2, Et3N, DCM; iv, for R' = Me, (a) Me3SiC1, EtOH, DCM; v, Na,R20H, CH2=CHCN ;vi, H2, Raney Ni, NH3 in EtOH; vii, 5M HCI, propylene oxide; viii, Me3SiBr, DCM; MeOH aq.; propylene oxide; ix, Me3SiCI, Et3N, THF; x, ZnC12, epichlorohydrin; xi, HOAc in MeOH; xii, NH3 in EtOH; x i , conc. HCI, heat; xiv, Et3N, ZNH(CH2)2CHO; xv, ZnCl2, N -(2,3-epoxypropyl)phthalimide.

Scheme 14

CbzNH

AfH -

+

Me02CLC02Me

-

CbzNH + C Q rM ,e)

I

OMe

0

0

F
H2N R

II

NH.HI MeSq ,NaOH NH2

b

or H2NCN, NH3

H

C02Me

0

I,H

H2NKNY NH R pO 'H

4: Quinquevalent Phosphorus Acids

143

agent such as NaBH3CN,224or, from (1-hydroxyalkyl)phosphonicesters through treatment of their mesylates with h y d r a ~ i n e . ~ ~ ~ As an example of developments in the phosphorus-containingpeptide field, the syntheses of (285), a tripeptidic (1-hydroxy-2-aminoalkyl)phosphonicacid, and some analogues, have been reported; the compound (285) itself is a good inhibitor of human renin.226

3.1.10 Sulfur and Selenium Containing Compounds. - The interaction of 0,Odialkyl methylphosphonothioates acid with POC13 to give the chloridates (286) and alkyl phosphorodichloridates parallels reactions of thiophosphoric esters already en~ountered.~~' The use of Lawesson's reagent to replace the phosphoryl bond in (1,l -difluoroalkyl)phosphonic esters by thiophosphoryl, has been noted (see also reference 258).169n228*229 The (Sp)-phosphinothioate (287) can be separated in pure, crystalline, form from the oily racemic mixture; the addition to it of selenium yields the phosphonoselenothioicester, oxidation of which, by iodine in water, affords the (RpRp)-diselenide (288).230Reactions between (Sp)-(287) and carbon tetrahalides C X 4 (X = C1 or Br)-Et,N yield the thiophosphonic halides (289), evidently with retention of configuration at phosphorus, since the anilide derived from them has a configuration known to be (Sp).230

3.I . 11 Phosphorus-Nitrogen Bonded Compounds. - Routes to thiophosphinoyl guanidines have been explored further,231and additional compounds with P-N bonds have been obtained from the corresponding phosphorus(II1) comp o u n d sometimes ~ ~ ~ ~ being separable into diastereoisomericforms.233 3.I . 12 Phosphorus Containing Ring Systems. - Further macrocyclic compounds have been obtained through interactions of the hydrazides (290) (X = 0, R = C1 or N3) and the dialdehydes (291) and between (290) (X = 0 or S, R = C1, N3 or Ph) and (292) (Y = 0, R = C1; Y = S, R = Cl or N3).234Compound (293) was obtained from the 2,2-bis(4-hydroxyphenyl)propane and PhP(NEt2)2followed by oxidation (X = 0)or sulfurization (X = S).235

144

Organophosphorus Chemistry

If encouraged to proceed further, some of the reactions already mentioned will allow ring formation to occur. In boiling benzene, the product (294) (Section 3.1.8)cyclizes to 1,2-dihydro-3-methoxy-l-methyl-2,5-diphenyl-l,3-azaphosphole 3-oxide (295)236and similarly in boiling benzene, the readily formed (296) (Ar = 4-fluorophenyl)cyclizes to the 2,3-dihydro-1,3-0xaphosphole(297).237 Ph. MeO,

0”

,C=CPh P \H

PhCH=NMe

*

MeO,

/C=CPh

P

0” \CHNHMe I Ph

EtO,

,C=CBu‘ P

o+ \ H

ArCHO base

--

EtO,

heat

’

Me

<$Ph

6‘ ‘OMe

,C=CBut

O”p\CHOH I

Ar

Reference has already been made to the formation of phospholanes from 1,4diketones and bis(trirnethylsily1)phosphonite. 153 The phosphorinanes (299) (R = H, Me, or Ph) have been obtained by using the same reagent and the appropriate 1,5-diketones (298); the linear compounds (300) were obtained as minor products; (298) (R = Ph) also gave stereoisomers of (301).238The dihydrophosphorine(302) undergoes a Diels-Alder reaction with acetylenedicarboxylic ester to give a mixture of stereoisomeric products, one of which could be purified and was shown by X-ray diffraction to have the configuration (303);239other Diels-Alder studies will be referred to later. The chlorophosphorinane 1-oxide (304) has been prepared via (305) and (306), the last from the quaternary salt (307).240

4: Quinquevalent Phosphorus A c i h

P

h O

h R

145

i, (Me3Si0)2PH

h

ii, H20 iii, CH2N2

0

(299)

+ 0 Ph A

‘\OMe P

h

Ph

O

R

0

(304) R =CI (305) R = O H (306) R - P h

(307)

An unusual 1,4-0xaphosphorinane was obtained (Scheme 15) initially from isopropyl phosphinate which was transformed, in three steps via (308) into the aldehyde (309); removal of the isopropylidene protection and acetylation gave a stereoisomericmixture of (31 1) with variable amounts of the acyclic enol acetates (310). Removal of the silyl protection from the former product, and acetylation gave the compounds (312) epimeric at phosphorus; one component was isolated in crystalline form and its structure confirmed by X-ray diffraction examination.241 ,CH=R

(308) R=CH2 (309) R = 0

(310) iii

(311) R = SiMqBu‘ (312) R = A c

C

Reagents: i, CF3C02H,H20, THF; ii, Ac20, py, DMAP; iii, KF, 18crown-6, Ac20

Scheme 15

Organophosphorus Chemistry

146

(313)

J Et203PY

f

R3

0, ,OEt

R3

Me3s!7 i?

Ph

'R3

(317)

1

Scheme 16

The silylation of carbanions derived from the phosphonic esters (313), is strictly a-regioselective, and proceeds through the stable carbanions (314) and on protonation, provides the phosphonates (315a-c) in high yield. The pathways for reactions between the silylated carbanions (314) and the aldehydes R3CH0 are depicted in Scheme 16. When the carbanions are acted upon by an aromatic aldehyde (R3= Ar), the products are the phosphorylated dienes (316) largely, if not completely, in the (a-form; on the other hand, if R is alkyl, the ( E ) / ( z )

4: Quinquevalent Phosphorus Acids

147

ratio is reversed (ca. 15:85). For both (314b) and (314c), a linear [(317), (319)] and a cyclic compound (a dihydro-l,2-oxaphosphorin)[(318), (320)] were the final products. Once again the nature of the aldehyde seems to have a pronounced effect. For (314b) with aromatic aldehydes, the products consist only of the corresponding (318), whereas for aliphatic aldehydes, substantial amounts of the dienes (317) are also formed. In the case of (314c) the outcome is the immediate formation of (320) at 50°C or that of (319) at 0°C; the latter is, in turn, convertible into (320) by the action of NaH in THF and heating to 50 OC.242 The racemic compounds (321) (R = octyl or Ph), synthesized by conventional means, were resolved by TLC; with HCl in diethyl ether, each diastereoisomer (322), (Rp)-(322) being cyclizes to give the chiral4H-1,3,2-benzodioxaphosphorin obtained from the corresponding (Rp)-(321).243 High yields of the 1,2-oxaphospholanes (324) are obtainable as (E)/(Z) mixtures (ca. 1:l to 2:l) by the action of Pd(OAc)2 on the acetylenic phosphonic esters (323).244

OH

C02Me

0 II

EtO-P-CGC-R I

Pd(0Ac)p LiCI,HOAc *

“‘“-;c O=P,

E d

O?= l,i

(323)

O

(324)

The addition of acyl hydrazides to (1,2-a1kadiene)phosphonic diamides (325) yields the 1,2,3-diazaphospholidine3-oxides (326).245Interaction of the phosphonite esters (327) (X = C1 or Br) with a,&unsaturated carboxylic esters, nitriles, ketones, or related compounds, gives quaternary products which decompose in boiling benzene to produce the dihydrophospholes(328).246 Ring formation has also been noted in the action of Lawesson’s reagent on 1aminoanthrones to afford the 1,3,2-oxazaphosphorines (329) (X = NH, NMe, or NPh);247the same reagent acting on (330) generates the 1,2,3-diazaphospholines (331) (X = 0 or S; R’,R2,and R3= H, Me, or Ph).248

3.2 Reactions of Phosphonic and Phosphinic Acids and their Derivatives. - An unusual example of cleavage of a phosphorus-carbon bond is that brought about in (2-phenyletheny1)phosphonicacids in the presence of 1,2,4-triazole and KOHMeOH.249

148

Organophosphorus Chemistry Me2N,

0

II (Me2N)2PCH=C =CR2

H2NNHCO$

WcHR2

P N ,,,,\

o'/

I

COR'

(326)

PhH; reflux -EtX

OMe

/

0

II

NNHR'

II

(R0)2PCH2CCHR2R3

(330)

Further esterification of monobenzyl benzylphosphonate may be carried through the Mitsunobu procedure, the best yields being achieved using the potassium salt of the substrate.250 Monoesters of N-protected (1aminoalky1)phosphonicacids are further esterified by alcohols in the presence of BOP-type reagents;251[(1-aminoalkyl)alkyl]- and [(1-aminoalkyl)aryl]-phosphinic acids, again as their potassium salts, have been converted into esters by reactive alkyl halides in the presence of 18-crown-6 ether (see also reference 278).252The synthesis of ethyl [bis(2,2,2-trifluoroethyl)phosphinoyl]acetatehas been described in It is useful to be aware that diisopropyl esters of phosphonic acids carrying additional functional groups can be dealkylated highly chemoselectively by MqSiBr in dioxane at 60°C.254A three-step sequence has been devised for the regioselective dealkylation of tetraalkyl esters of dichloro- and dibromo-methylenebis(phosphonic)acids to leave the P,P-dialkyl esters.25s In the attempted preparation of phosphonochloridates (332) (X = Cl) from (332) (X = OH) by the action of thionyl chloride, the anhydrides (333) are also formed; these are also reactive to alcohol and amine nucleophiles although much less so than the phosphonochloridates. More interestingly, the phosphonochloridates, when treated with triethylamine, generate the highly reactive phosphonoylating agents (334).256 The action of thionyl chloride on the esters (335) (R = Et) proceeds normally with the replacement of OR2 by Cl,but reaction takes place at nitrogen with no replacement of the ester group when R = Me.257

4: Quinquevalent Phosphorus A c i h 0

0 II

II

RHN-P-OEt XI

RHN-

149 0

0

I1

II

P-0-P-NHR EtO I OEt I

RHN-P-OEt

+kt,Cr

0

II,0R2 R'VP\ OCH2CH2NR2

Denmark and his colleagues have studied the stereochemical course of the alkylation of phosphoryl and thiophosphoryl stabilized carbanions based on the perhydro-l,3,2-oxazaphosphorinesystem. They used as their model substrates the compounds (336) (a-c) and (337) (a-c) in both the cis- (illustrated) and trans(epimeric at phosphorus) forms with, as the alkylating agents RX, MeI, BuI, Bu'I, and BnBr. The diastereoselectivity of alkylation of cis (336) is highly dependent on R' and on the electrophile, being good (40:l) for (a) and (b) but poor (2-3:l)for (c); a similar trend was observed for the thiophosphoryl series (337a-c) and, in addition, modifications to selectivity, even so far as a complete reversal, can be achieved by the addition of selected substances e.g. HMPA. Considerable improvements in diastereoselectivitywere noted for the trans-(337) series. Carbanion formation with Bu'Li in THF of the alkylated products, and reprotonation, can lead to significant enrichments (1:l to 5:l) in the minor components not easily accessible by the first stage a l k y l a t i ~ n . ~ ~ ~ . ~ ~ ~

(336)X = 0 (337)x = s (a) R1 = Ph (b) R' = Me (c) R' = Me0

The arylation of (338) by ArI to give (339) occurs in the presence of triethylamine and ligand-free Pd, generated from the acetate, and affords very high yields, stated to be even greater for reactions in aqueous DMF containing hydrogencarbonate; the same products are also obtained when aroyl chlorides are so used.260The conjugate addition of organocuprates R12CuX to the carboncarbon double bond in (338) (R = H)proceeds to give (340) after protonation.261 The cyclic phosphonamidic chloride derived from (-)-ephedrine is unreactive to vinylic metallic reagents.262

k (338)

R

(339)

(340)

150

Organophosphorus Chemistry

All three (fluorobenzy1)phosphonic acids have been sulfonated at room temperature (monosulfonation) or at 80 "C (disulfonation) by high proportions of S03.263

Carbon-carbon bond formation takes place in reactions between N,N-dialkylanilines and dialkyl(2-nitroetheny1)-and (2-bromo-2-nitroethenyl)-phosphonates in acetic acid solution; in the former case, the reaction is effectively one of addition across the C=C bond, and in the second case, replacement of bromine occurs with attachment of the amine moiety on the adjacent sp2carbon and with no concomitant reduction.264 Arsenic-containing ylides are better reagents than the corresponding phosphorus compounds for additions to alkenylphosphonic diesters as a route to cyclopropylphosphonic dies x ~ ! - ~ O M e ) ~

0

Two papers have extended our knowledge of the scope of phosphonoyl carbene (342) reactivity towards phosphite triesters. The first communication examines their obtention from (341) where X is a simple n-alkyl group, MeS, EtS, or EtO. When X = 2-Me, the main reaction is that of intramolecular trapping to give an ylide (343), but for the other cases (the substituent then having a central chain of two or more atoms), intramolecular reactions between the carbon centre and the substituent were also observed. Unusually, for X = 2MeS, a greater preference (65-700/) for intermolecular trapping by the phosphite throughout the whole reaction temperature range was observed. When cyclization was observed, there was a marked preference for the formation of fivemembered rings.266In the second communication, the list of examined substrates was extended to include those in which X = 2-Ph0, 2-PhOCH2, and 2-PhS. Here, alternatives to the accumulation of ylide (343) were the formation of (344) with or without (345) but also, and more importantly, intramolecular trapping through carbene insertion into the 2-aromatic system. When X = PhO, the formation of (346) (2 = 0) accounted for about two-thirds of the acylphosphonate (341) destroyed; the remaining third led mostly to ylide accompanied by traces of bisphosphonic esters. When X = 2-PhS, the formation of ylide accounted for about 60% of the total reaction product, and was accompanied by (346) (Z = S ) and (347) (2 = S), formed from the carbene, in the ratio 1:2. A more detailed investigation of the rearrangement of the carbene (342) (X = 2PhS) into (347) (Z = S ) provided evidence for the formation of a spirodiene intermediate. Finally, for X = 2-PhOCH2, the products were the ylide together with a small quantity of (348).267 The ready cleavage of the P-C bond in esters of (1,l -difluoro-2-oxoalkyl)phosphonic acids forms the critical step in a scheme for the conversion of aldehydes

4: Quinquevalent Phosphorus Acidr

151

(346)

(Et0)2!&0

R’

R2 (350)

(349)

.!EL<

(353)

R3

(RCHO) into the ketones RCOCHF2 following an initial reaction with diethyl (lithiodifluoromethyl)phosphonate.268 The dephosphonoylation of diethyl (2oxo-2-phenylethy1)phosphonate has been observed on attempted LiAlH4 reduct i o n ~ . Reactions *~~ between (349) (E = Ac, CN, or COOEt; R’,R2 = H, Me, or Ph) and hydrazines (R = H, Me, or Ph) provided the corresponding (350) ( YH = OH, NH2, or CH3)F70 For (351) in which R3 = H, But, or Ph, and R’ R2are H, Me or (CH2)3, the products are (352) (R = H)when R = H, or mixtures of (352) and (353) (in the ratios 80:20 to 0:lOO)when R = Me or Ph.*” The reactivity of phosphonate carbanions towards five- or six-membered alkenones (354) with a hetero group Z has been shown to be chemoselectively controlled by the nature of the group Z. When Z = C1, reaction affords the compounds (355) and these, when acted upon by acidic reagents (Scheme 17) undergo dehydration leading to (356) or (357). Exceptionally, 3-chlorocyclopentenone leads to (363).272When Z = OMe, the initial reaction leads to (358) (R’, R2 = H or Me), and both this type of intermediate, and the already recorded

152

Organophosphorus Chemistry

lv

I

P03Et2

(359) Reagents: i, H2S04, CHClj ii, pTsOH, CsHs; iii, MeOH; iv, 12, MeOH; v,

I2

Scheme 17

(355) can act as precursors to arylmethyl phosphonic derivatives. Thus, a treatment of (358) with iodine in MeOH leads to the compounds (359), and a similar treatment of (355) (Z = Me) leads, via (360), to (361) or its demethoxylated derivative (362).273 Renewed efforts have been made to sterically control the Michael addition of allylic phosphonate carbanions to cyclic enones. The anions generated by the

4: Quinquevalent Phosphorus A c i h

153

(a-

action of BuLi on (364) (R = H) and and (2)-(364) (R = Me), when acted upon by cyclopentenone, yield diastereomerically enriched products of conjugate addition, (365), cleavable at the ethylenic double bond by ozone to give a dicarbonyl In a second study, allylic carbanions based on the perhydro-l,3,2-oxazaphosphorinesystem (367) [R'= H (cis and trans) or Me; R2 = Pr', But, CEt,, or (5')-PhCHMe] were made to react with cycloalkenones (366) (n = 1 - 3). Reaction was possible at either the a or y positions of the carbon side chain, and 1,2- or 1,4- with respect to the cycloalkenone; in addition stereoisomerism at phosphorus was possible for reactions based on (367) (R' = H). For the latter group, the products (370) were not detected and the ratio of (369) to ( 368) was, when determined and then with one exception, within the range 24:l to 99:1, irrespective of structural actors. For the cis-series, high regio- and diastereo-selectivities (88-90% d.e.) could be obtained, whereas for the trans-series, the reactions were not particularly diastereoselective (ca. 10% d.e.). High specificity has been rationalized in terms of the structure and conformational preferences of the ally1 carbanion, conformational analysis of the oxazaphosphorine ring, and the nature (10-membered ring) of lithium coordinati~n.~'~

(365)

Z=

\

(367)

Z=

(368)

Z=

1-

R2

\ (CH2)"

154

Organophosphorus Chemistry

Ally1 ethers of dialkyl (hydroxymethy1)phosphonates (371) undergo Wittig and (3rearrangements, under the influence of bases, to give mixtures of the (I -hydroxyalkyl)phosphonates (372) and (373). The total yields and stereoisomeric compositions of the products depend on the nature of the base; whereas the bases (Me3Si)NM (M = Li or K) lacked activity, BuLi produced moderate yields, but the best total yields (88%) were obtained with LDA, and the (E)l(Z) ratios were (R' = Me or Pr') ca. 4:l. For other cases (R' = H, R2 = Me) the antdsyn product ratios could be very high.276In another study, an attempt to control stereochemistry with R = menthyl produced a diastereoisomeric ratio 96:4 for (371) (R = menthyl, R' = R2 = H); this allowed a synthesis of (R)- and (S)-(lhydroxybuty1)phosphonicacids and their dimethyl esters.277An examination of the rearrangement of compounds (374) into (379, together with that of the compounds (3747, epimeric at phosphorus, into (375'), introduced an additional factor, namely chirality at phosphorus and the possibility of asymmetric rearrangement. The rearrangements of (374a) and (374'a) each yielded largely single diastereoisomeric products (with 74% yields), and there was therefore no epimerization at phosphorus; moreover, for each of the remaining cases, when small amounts of second products were formed, it could be reasonably assumed therefore that these were epimers at the stereogenic carbon centre. However, in all cases of (374b) and (374'b,c) diastereoisomer ratios in the products were greater than 9O:lO. Once again, acidic hydrolysis of the products, followed by methylation (diazomethane) yielded diastereoisomeric dimethyl (2-methyl-1-hydro~ybuty1)phosphonates.~~~

(a-

(374)

(a) R1 = R2 = H (b) R1 = Me, R2 = H (c) R1=H, R 2 = M e

(375)

Although stereochemically pure (376) (X = Cl) reacted with trimethyl phosphite to give stereochemically pure (376) [x = (MeO),P(O)], other ratios of (376) (X = Cl) and (377) (X = C1) reacted non-specifically. Attempted purification of the phosphonic dimethyl esters by distillation results in their rapid decomposition,

4: Quinquevalent Phosphorus A c i h

155

but when the diester is kept in solution (CHC13) for 6 days, pure (376) [x = (Me0)2P(0)] evidently equilibrates with a cis-form, and an internal hetero DielsAlder process affords a mixture containing (378), a transformation catalysed by the presence of ~ y r i d i n e . ~Diels-Alder ’~ reactions of diethyl (3-0x0-1-butenyl)phosphonate have been studied;280the course of that involving addition of the same phosphonate to 1-acetyloxy-l,3-butadienedepended on the presence of a Lewis acid catalyst, when the nature of the single product (379) was such as to require extensive NMR spectroscopic study for a solution to its structure.281

(376)

(377)

(379)

The phosphonates (380) (where Z is a 1,2-ethanedioxyor 1,3-trimethylenedioxy moiety and Ar = Ph or 4-substituted phenyl) are well-characterized compounds obtained from the appropriate diol and a phosphonic dichloride in the presence of Et,N in a solvent. It has long been known that it is possible to obtain isomeric products when the order of mixing of the reactants is changed; these are also the products from the rearrangements of (380). Thus, when kept in dichloromethane/ DMSO at 80°C for 8 h, (380a) affords 75-80% of (381) (X = Cl). The rearrangement is facilitated by the replacement of a weak electron donor group X = Me by an acceptor group e.g. X = C1.282 The photolysis of a mixture of the alkene RCH=CH2 and (382) afforded (383) in good to high yields.283The treatment of a large variety of a-thiomethyl- and aselenomethyl phosphonates with Bu3SnH-AIBN results in their desulfurization or d e ~ e l e n a t i o n .The ~ ~ ~deselenation of phosphinoselenoic esters, e.g. (384), occurs under attack by organometallic reagents, and ensuing reaction with alkyl halides provides phosphine oxides.285

(380) (380a)Z = PhCHCHPh Ar = 4-CICsH4

(381)

(382)R1= SePh (383)R1 = CH2CR(SePh)

(384)

The attack on (385) by a primary amine results in the initial cleavage of the PC1 bond to give (386) (R = Et or Ph); on the other hand initial displacement within (387) occurs at carbon to give (388), followed by attack at phosphorus to

156

Organophosphorus Chemistry

give (389).286Under photolytic inducement, a retro-Diels-Alder process leads to the elimination of (390) from its adduct with a phosphorin; its formation is characterized by its entrapment in EtOH, affording (391), obtainable also by the addition of the secondary amine to (392).287 Me

Me

CI

CI

(385)X = C I (386)X=NHR

(387)X = Y = CI (388)X = CI,Y = R2N (389)X = Y = R2N

The compound (393) is several hundred times more reactive than (394) towards simple nucleophiles such as Et2NH, suggesting a difference in the mechanism of chlorine replacement. Bearing in mind the acidity of the a-proton in (393), it was suggested that nucleophilic displacement of chlorine in the latter proceeded via (395).288The rearrangement of N,O-di-derivatives of hydroxylamine (396) under conditions of basic catalysis have been considered, in the light of stereochemical changes, to proceed through (397). More recently, however, the possibility of participation of mixed anhydrides such as (398) has also been seriously considered, although direct evidence for either (397) or (398) is lacking. Mixed anhydrides such as (398) (R' = Ph or PhCHMe, R2 = Me) have now been synthesized and shown to be highly reactive, not unexpectedly. When R' was PhCHMe (resolved), the principal product obtained from the action of Bu'NH2 was a diastereoisomeric mixture of the corresponding (399) of a composition which, however, is dependent on the relative concentration of the amine [similar

(393)

(394)

(395)

4: Quinquevalent Phosphorus Acids

157

to that reported for (396)], together with a substantial amount of the symmetrical anhydride (400); the latter is also produced from the mixed anhydride on hydrolysis. Incidentally, the action of an amine on the mixed anhydride (398) (R2 = Me) produced no sulfonamide but with R2 = 4-nitrophenyl, some sulfonamide was isolated; evidence was presented, however, to suggest that this was not obtained directly from the mixed anhydride, but rather from a substance derived from it. Nevertheless, in spite of some confusing evidence, mixed anhydrides are now seriously considered as intermediates in the base-catalysed rearrangement of the hydroxylamine drivatives (396).289p290

*

R:

p

IP\

R2SOz0

4

NHPh

R3NH2

[Ph:

+P=O

R:

00

Y\ NHR3 PhHN

Structure

A very large amount of NMR spectroscopic data has been collected during the year under review. The presentation of 13C data in addition to 31Pdata is now almost routine. NMR spectroscopic studies have now been presented for phosphonocarboxylic acids and their esters,291some new phosphinic a m i d e ~ , ~ ~ ~ and for Lawesson’s reagent (solid and solution data).293A spectroscopic study of the dimer of the nitrile oxide (401) suggested the structure (402).2” 1-(1Naphthaleny1)ethylamine and ephedrine are recommended for the 3*P NMR spectroscopic determination of the enantiomeric composition of (1 -aminoalkyl)p h o ~ p h o n a t e s but , ~ ~ of ~ quinine and tert-butylphenylphosphinothioicacid, only the former was effective for the chiral resolution of the diethyl esters in the determination of e.e.s of (2-hydroxyalkyl)pho~phonates.~~~ Conformational analyses, based on NMR spectroscopic data, have been carried out for dialkyl(2hydroxyalky1)phosphonates.297

158

Organophosphorus Chemistry

it

0 (405) X=CH2 (406) X = S e

(404)

Solution and solid state spectroscopic work on dimethyl (2-hydroxy-3benzoylpropy1)phosphonate was accompanied by a single crystal X-ray anal y ~ i s Other . ~ ~ ~ single crystal X-ray diffraction determinations on hydroxy phosphonates include those of diethyl (1 -hydroxybutynyl)ph~sphonate;~~~ diphenyl (1-hydroxy-1-phenylethyl)phosph~nate;~~ cis- and t r ~ n s- ( 4 0 3 ) ;and ~~~ 0

0

CPh

Me

H

4: Quinquevalent Phosphorus A c i d

159

two crystalline forms of (404).302Other compounds examined include the nitrile oxide (401);303the methylenebisphosphonic derivative (405)304and the selenide (406);305 the acid (407);306 the phosphonic ester (408);307 the phosphonic diamides (409) and (410),308and (41l);309the chloridate (412);18*the phosphonic diester (413) (demonstrating coordination netween the amino group and phosp h o r ~ ~ ) the ; ~ 'system ~ (414);31*and the triphospholane (415) (Ar = 2,4,6-tritert-b~tylphenyl);~~~ d i b e n ~ o -and ~ a dinaphtho-lO [1,3,6,2]dioxathiaphosphocin oxides; the system (4) (X = 0, R = Me, and Ar = 2,6-dimethylphenyl);11 diphenyl (ferro~eny1methyl)phosphonate;~~~ compounds (416) epimeric at C*; 141 and (336a) (R = Me).258 Aminoalkyl phosphonic derivatives examined include (2-amino-1-fluoroethyl)phosphonic acid;lS5 [(3-amino-2-hydroxypropyl)methyl]phosphinic acid;219 (guanidinophenylmethy1)phosphonic (2-amino-2-phenylethy1)phosphonic acid;183 and ( -)-(aminocyclohexylmethy1)phosphonic acid and its Mosher derivative.182

S Ar-P

S

Among the sulfur (and selenium) compounds which have been examined are Lawesson's reagent;262diphenylphosphinoselenoicacid and its anhydride;314two stereoisomers of (417);315 the truns-l,3,2,4-oxathiadiphosphetane disulfide (418) (Ar = 2,4,6-triisopropylphenyl), isolated from the crude product in the synthesis of the corresponding 1,3,2,4-dithiadipho~phetane;~l~ cholesterol derivatives in the 1,3,2-0xathia- and 1,3,2-dithia-phospholaneseries;317one 2-dialkylamino-1,3,2-dioxaphosphepin 2-sulfide and an analogous 2-~elenide;~l~ the dinaphthodioxaphosphocinsulfide (3) (Z = CH2, X = S, R = OCsI&Me-4);319the tetrathiadiphosphorin derivative (419) obtained from 1,2-diphosphinobenzene

Organophosphorus Chemistry

160

and and the similar system (420),321and (421).322The synthesis and Xray analysis of stereoisomers of (422) (R = Cl)323and (422) (R = Ph and OPh)324 have been recorded. X-ray powder data (together with 3'P NMR data) have been listed for (aminomethy1ene)bisphosphonicacids.325 Mass spectral data have been presented for a series of dithiaphosphepins (423) (R = alkyl, cycloalkyl, phenyl and a r y l o ~ y ) . ~ * ~

t Ab initio calculations have been performed for (1ithi0alkyl)phosphonates~~~ and, together with NMR and chiroptical studies, for methyl methylphosphonofluoridate.328Finally, steric and stereoelectronic effects in 1,3,2-dioxaphosphorinanes have been discussed.329

References 1. 2. 3. 4. 5. 6. 7.

8. 9. 10. 11. 12. 13. 14. 15.

Ya. A. Dorfman, M. M. Aleshkova, and F. Kh. Faizova, Russ. J. Gen. Chem., 1995, 65, 508. Ya. A. Dorfman, M. M. Aleshkova, and F. Kh. Faizova, Russ. J. Gen. Chem., 1995, 65,1309. Ya. A. Dorfman and M. M. Aleshkova, Russ.J. Gen. Chem., 1995,65,515. Yu. G . Budnikova and Yu. M. Kargin, Russ. J. Gen. Chem., 1995,65,504. P.M. Reddy, B. S.Reddy, C. D. Reddy, and K. D. Berlin, Indian J. Chem., Sect. B, 1995,34,1085. B. S. Reddy, C. D. Reddy, P. M. Reddy, and C. N. Raju, Indian J. Heterocycl. Chem., 1994,4,117. C . D. Reddy, B. S. Reddy, K. Anuradka, K. D. Berlin, S. M. Naidu, and M. Krishnaiah, Bull. Chem. Soc. Jpn., 1995,68,3459. P . M. Reddy, B. S.Reddy, and C. D. Reddy, Heteroat. Chem., 1996,7,165. K. Anuradha, B. S. Reddy, C. D. Reddy, K. D. Berlin, K.M. Couch, and S . Tyagi, Indian J. Heterocycl. Chem., 1995,5, 15. B. S. Reddy, K. Anuradha, C. R. Reddy, N. J. Kumar, M. Krishnaiah, and K. D. Berlin, Heteroat. Chem., 1995,6,485. C. D. Reddy, B. S.Reddy, M. S.Reddy, S. M. Naidu, and K. D. Berlin, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995,102, 103. B. S. Reddy, K. V. Raghu, M. S. Reddy, and C. D. Reddy, Indian J. Heterocycl. Chem., 1995,4,229. U . Neidlein and F. Diederich, J. Chem. Soc., Chem.Commun., 1996,1493. L. N. Markovsky, M. A. Visotsky, V.V. Pirozhenko, V. I. Kalchenko, J. Lipkowski, and Y. A. Simonov, J. Chem. Soc. Chem. Commun.,1996,69. R. G. Jansen, J. P. M. van Duynhoven, W. Verboom, G. J. van Hummel, S.Harkema, and D. N. Reinhoudt, J. Am. Chem. SOC.,1996,118,3666.

4: Quinquevalent Phosphorus A c i h 16. 17. 18. 19. 20. 21.

161

V. I. Kal’chenko, M. A. Bysotskii, V. V. Pirozhenko, A. N. Shivanyuk, and L. N. Markovskii, Russ. J. Gen. Chem., 1994,64,1560. J. Gloede and I. Keitel, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,104, 103. 0. Aleksuik, F. Grynszpan, and S. E. Biali, J. Inclusion Phenom. Mol. Recognit. Chem., 1994,19,237. V . I. Kal’chenko, A. N. Shivanyuk, V. V. Pirozhenko, and L. N. Markovskii, Russ. J. Gen. Chem., 1994,64,1397. A. N. Shivanyuk, V. I. Kal’chenko, V. V. Pirozhenko, and L. N. Markovskii, Russ. J. Gen. Chem., 1994,64,1394. A. Vollbrecht, I. Neda, and R. Schmutzler, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,107,173.

22. 23. 24. 25. 26, 27.

B. V. L. Potter and D. La m p, Angew. Chem.. Int. Ed. Engl., 1995,34,1933. S-K. Chung, Y-T. Chang, and K-H. Sohn, J. Chem. SOC.,Chem.Commun.. 1996,163. T. Sawada, R. Shirai, Y. Matsuo, Y. Kabuyama, K. Kimura, Y. Fukui, Y. Hashimoto, and S . Iwasaki, Bioorg. Med Chem. Lett., 1995,5,2263. S-K. Chung and S-H. Yu, Bioorg. Med. Chem. Lett., 1996,6,1461. A. M. Riley and B. V. L. Potter, J. Org. Chem., 1995,60,4970. D. J. Jenkins, D. Dubreuil, and B. V. L. Potter, J. Chem. SOC.Perkin Trans. I , 1996, 1365.

28. 29.

P. Guedat, M. Poitras, B. Spiess, G. Guillemette, and G. Schlewer, Bioorg. Med. Chem. Lett., 1996,6, 1175. N. Schnetz, P. Guedat, B. Spiess, and G. Schlewer, Bull. SOC.Chim. Fr., 1996, 133, 205.

30. 31. 32. 33. 34. 35. 36. 37. 38. 39.

40. 41. 42. 43.

44. 45. 46. 47. 48.

J. Schulz, J. Wilkie, P. Lightfoot, T. Rutherford, and D. Gani, J. Chem. SOC.,Chem. Commun., 1995,2353. A. Berkessel,U. Geisel, and D. A. HCrault, Tetrahedron Lett., 1996,37,355. T. Vorherr and W. Bannwarth, Bioorg. Med. Chem. Lett., 1995,5,2661. T. Wakamiya, T. Nishida, R. Togashi, K. Saruta, J. Yasuoka, and S . Kusumoto, Bull. Chem. SOC.Jpn., 1996,69,465. Y-M. Li, Y. Jin, Y-C. Li, and Y-F. Zhao, Phosphorus, Sulfur. Silicon, Relat. Elem., 1995,101,141. A. Otaka, K. Miyoshi, M. Kaneko, H. Tamamura, N. Fujii, M. Nomizu, T. R. Burke, and P. P. Roller, J. Org. Chem., 1995,60,3967. C . D. Reddy, P. M. Reddy, D. B. Reddy, M. Nagalakshmamma, K. Anuradha, C. N. Raju, K. D. Berlin, K. M. Couch, and S . Tyagi, J. Heterocycl. Chem., 1995, 32, 1483. B. S. Reddy, C. D. Reddy, and P. M. Reddy, Indian J. Heterocycl. Chem., 1995,4,219. C. D. Reddy, B. S. Reddy, and T. A. Hanumantharayudu, Orient. J. Chem., 1995, 11,35; Chem. Abstr., 1995,123,198917. P. M. Reddy, B. S. Reddy, and C. D. Reddy, Indian J. Heterocycl. Chem., 1995, 4, 215. Y.Watanabe, S. Inoue, T.Yamamoto, and S . Ozaki, Synthesis, 1995,1243. J. M. Hill and G. Lowe, J. Chem. Soc., Perkin Trans. I , 1995,2001. D. Robert, M. Curci, J-L. Mieloszynski, and D. Paquer, Bull. SOC.Chim. Fr., 1994, 131,1015. D. Robert, J.-L. Mieloszynski, and D. Paquer, Phosphorus, Sulfur, Silicon, Relat. Elem., 1994,97,83. W. Kudelska and M. Michalska, Synthesis, 1995, 1539. I. S. Nizamov, L. A. Al’Metkina, G. G. Garifzyanova, G. G. Sergeenko, and E. S . Batyeva, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995,102,7 1. I. S. Nizamov, L. A. Al’Metkina, and E. S . Batyeva, Russ. J. Gen. Chem., 1994, 64, 1399. I. S. Nizamov, G.G. Garifzyanova, and E. S . Batyeva, Russ. J. Gen. Chem., 1995, 65,143. I. S. Nizamov, G. G. Garifzyanova, and E. S . Batyeva, Izvest. Akad. Nauk. SSR, Ser. Mtim., 1994,43,765; Chem. Abstr. 1995,123,83514.

162 49.

50. 51. 52. 53. 54. 55.

56. 57. 58.

59. 60. 61. 62. 63.

64. 65. 66. 67. 68.

69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85.

86.

Organophosphorus Chemistry

M. I. Kabachnik, L. S. Zakharov, G. N. Molchanova, P. V. Petrovskii, T. M. Shcherbina, and A. P. Laretina, Russ. J. Gen. Chem., 1995,65, 17. F. Hammerschmidt and A. Hanninger, Chem. Ber., 1995,128,823. D. Crich, Q. Yao, and G. F. Filzen, J. Am. Chem. SOC.,1995,117, 11455. H. Quast and T. Dietz, Synthesis,1995, 1300. S. N. Munik, V. N. Eliseenkov, and B. E. Ivanov, Russ. J. Gen. Chem., 1995,65,378. J . Wasiak, J. Henliski, W. Dabkowski, Z. Skrzypczynski, and J. Michalski, Pol. J. Chem., 1995,69,1027. M. Nakamura, K. Sawasaki, Y. Okamoto, and S. Takamuku, Bull. Chem. SOC.Jpn., 1995,68,3189. M. Nakamura, Y. Okamoto, and S. Takamuku, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,106,137. M. Nakamura, Y. Okamoto, and S. Takamuku, J. Chem. SOC.,Chem.Commun., 1996,209. C. Lowe, J. Pauli, and L. Riesel, Z. Anorg. Allg. Chem., 1995,621,894. K . Gholivand, A. H. Mahmoudkani, and M. Khosravi, Phosphorus, Sulfur, Silicon, Relat. Elem, 1995, 106, 173. A. B. Ouryupin, M. I. Kadyko, P. V. Petrovskii, E. I. Fedin, A. Okruszek, R. Kinas, and W. J. Stec., Tetrahedron; Asymmetry, 1995,6, 1813. J . W. Perich, P. F. Alewood, and R. B. Johns, Phosphorus, Sulfur, Silicon, Relat. Elem.. 1995,105, 1. F. A. Merckling and P. Rueedi, Tetrahedron Lett., 1996,37,2217. M. Wang, S. Z. Liu, J. Biu, and B. F. Hu, Chin. Chem. Lett., 1995,6,959. M. Mentz and T. A. Modro, J. Chem. SOC.,Perkin Trans. 2, 1995,2223. A. G. Cole, J. Wilkie, and D. Gani, J. Chem. SOC., Perkin Trans. I , 1995,2695. J. Wilkie, A. G. Cole, and D. Gani, J. Chem. SOC.,Perkin Trans. I , 1995,2709. M. Mentz and T. A. Modro, J. Chem. SOC.,Perkin Trans. 2, 1995,2227. J. S. Rosenblum, L-C. Lo, T. Li, K. D. Janda, and R. A. Lerner, Angew. Chem., Int. Ed. Engl., 1995,34,2275. T . C. Bruice, A. Blaskb, and M. E. Petyak, J. Am. Chem. SOC.,1995,117,12064. T. C. Bruice, A. Blaskb, R. D. Arasasingham, and J-S. Kim, J. Am. Chem. SOC., 1995,117,12070. W . B.Chen, F. L. Yang, and Z. J. Liu, Chin. Chem. Lett., 1995,6, 1021. A. Skowronska, P. Dybowski, M. Koprowski, and E. Krawczyk, Tetrahedron Lett., 1995,36,8129. A. Skowronska, P. Dybowski, M. Koprowski, and E. Krawczyk, Tetrahedron Lett., 1995,36,8133. V . Dodin-Carnot, M. Curci, J. C. Wilhelm, J. L. Mieloszynski, and D. Paquer, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,107,219. K. Fukushima, A. Kanayama, Y. Matsumoto, S. Ono, T. Yoshimura, H. Morita, E. Tsukurimichi, and C. Shimasaki, Bull. Chem. SOC.Jpn., 1996,69,367. A. Zwierzak and A, Napieraj, Tetrahedron,1996,52,8789. N. Oget, F. Chuburu, J. J. Yaouanc, and H. Handel, Tetrahedron, 1996,52,2995. Q-J. Yan, Q. Wang, and Y-F. Zhao, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 107,181. T. Wakamiya, K. Saruta, J. Yasuoka, and S. Kusumoto, Bull. Chem. SOC.Jpn., 1995,68,2699. C.C. Orji, and A. G. Pinkus, Org. Prep. Proced Int., 1994,26,691. J-M. Grtvy and M. Mulliez, J. Chem. SOC.,Perkin Trans. 2, 1995, 1809. C. C. Tang, G. P. Wu,S. J. He, and Z. J. He, Phosphorus, Sulfur, Silicon, Relat. Elem.. 1995,l01,91. C-C. Tang, H-F. Lang, and Z-J. He, Heteroat. Chem., 1996,7, 207. L. D. Quin, P. Hermann, and S. Jankowski, J. Org. Chem., 1996,61,3944. K. Troev, Rev. Heteroat. Chem., (a) 1994,11,89; (b) 1995,12,85; (c) 1995,13,99. R.S. Edmundson, in ‘The Chemistry of Organophosphorus Compounds’, ed. F. R. Hartley, John Wiley, Chichester, 1996, vol. 4, chapters 2-5.

4: Quinquevalent Phosphorus Acidr 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99.

100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126.

163

R. S. Edmundson, in ‘The Chemistry of Organophosphorus Compounds’, ed. F. R. Hartley, John Wiley, Chichester, 1996,vol. 4, ch. 6. E. A. Anisimova, Yu. N. Mitrasov, and V. V. Kormachev, Russ. J. Gen. Chem., 1994,64,1402. E. A. Anisimova, Yu. N. Mitrasov, V. V. Kormachev, and P. I. Fedorov, Russ. J. Gen. Chem., 1994,64,1403. I. E. Gurevich, J. C. Tebby, A. V. Dogadina, and B. I. Ionin, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 101,267. E. V. Erokhina, E. A. Shokova, Y. N. Luzikov, and V.V. Kovalev, Synthesis, 1995, 851. R. I. Yurchenko and L. P. Peresypkina, Russ. J. Gen. Chem., 1994,64,1398. 0.I. Kolodyazhnyi and E.V. Grishkun, Russ.J. Gen. Chem., 1994,64,1547. 0. I. Kolodyazhnyi and E. V. Grishkun, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,103,191. C. F. Zhu and H. Y. Xiao, Chin. Chem. Lett., 1995,6,565. L. M. Pevzner, V. M. Ignat’ev, and B. I. Ionin, Russ. J. Gen. Chem., 1995,65,877. L. M. Pevzner, V. M. Ignat’ev, and B. I. Ionin, Russ. J. Gen. Chem., 1994,64, 1754. D. Witt and J. Rachon, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,107,33. C. G. Caldwell, S. P. Sahoo, S. A. Polo, R. R. Eversole, T. J. Lanza, S. G. Mills, L. M. Niedzwiecki, M. Izquierdo-Martin, B. C. Chang, R. K. Harrison, D. W. Kuo, T. Y. Lin, R. L. Stein, P. L. Durette, and W. K. Hagmann, Bioorg. Med. Chem. Lett., 1996,6, 323. P. Jubault, C. Feasson, and N. Collignon, Tetrahedron Lett., 1996,37,3679. J. F. Koszuk, Synth. Commun., 1995,25,2533. M . F. Probst and T. A. Modro, Heteroat. Chem., 1995,6,579. Y. J. Koh and D. Y. Oh, Synth. Commun., 1995,25,2587. K. Fettes, L. McQuire, and A. W. Murray, J. Chem. SOC.,Perkin Trans. 1, 1995,2123. J-P. Bigui, D. Bonnet-Delpon, and M. H. Rock, J. Chem. SOC.,Perkin Trans.1, 1996, 1409. A. Burini, S.Cacchi, P. Pace, and B. R. Pietroni, Synlett., 1995,677. X. Huang, C. Zhang, andX. Lu, Synthesis, 1995,769. C. Ma, X. Lu, and Y. Ma, Main Group Met. Chem., 1995,18, 391. C. L. Ma, X. Y. Lu, and Y. X. Ma, Chin. Chem. Lett., 1995,6,747. J. E. Hong, C-W. Lee, Y. Kwon, and D. Y. Oh, Synth. Commun.,1996,26,1563. R. Dizike and P. Savignac, TetrahedronLett., 1996,37,1783. Z . S . Novikova, N. N. Demik, A. Yu.Agarkov, and I. P. Beletskaya, Russ. J, Org. Chem., 1995,31,129. E. A. Boyd, M. E. K. Boyd, and V. M. Loh, Tetrahedron Lett., 1996,37, 1651. R. Beugelmansand M. Chbani, Bull. SOC.C h h . Fr., 1995,132,290. W. Huang and C. Yuan, Synthesis, 1996,511. D. K. Anderson, D. L. Deuwer, and J. A. Sikorski, J. Heterocycl. Chem., 1995, 32, 893. Yu. L. Zborovskii, V. F. Levon, and V. I. Staninets, Russ. J. Gen. Chem., 1994,64, 1401. F. Palacios, J. Garcia, Ana M. Ochoa de Retana, and J. Oyarzabel, Heterocycles, 1995,41,1915. A. Caprita, G. Ilia, and M. Tugui, Rev. Chim (Bucharest), 1995,46, 117. A-R. Li and Q-Y. Chen, Synthesis, 1996,606. D. B. Berkowitz and D. G. Sloss, J. Org. Chem., 1995,60,7047. W . Qiu and D. J. Burton, TetrahedronLett., 1996,37,2745. S. R. Piettre, Tetrahedron Lett., 1996,37,2233. T. F. Herpin, J. S. Houlton, W. B. Motherwell, B. P. Roberts, and J. M. Weibel, J. Chem. SOC.,Chem. Commun., 1996,613. D. Green, S. Elgendy, G. Patel, J. A. Baban, E. Skordalakes, W. Human, V. V. Kakkar, and J. Deadman, Tetrahedron, 1996,52, 10215. P. Jubault, C. Feasson, and N. Collignon, TetrahedronLett., 1995,36,7073.

164

Organophosphorus Chemistry

127.

K. Blades, G. S. Cockerill, H. J. Easterfield, T. P. Lequeux, and J. M. Percy,

128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163.

J. Chem. SOC.Chem. Commun.,1996,1615. S . Sebti, A. Rhihil, A. Saber, M. Laghrissi, and S . Boulaajaj, Tetrahedron Lett., 1996,37,3999. T. Arai, M. Bougauchi, H. Sasai, and M. Shibasaki,J. Org. Chem., 1996,61,2926. P. G. Devitt and T. P. Kee, Tetrahedron,l995,51,10987. P. G. Devitt, M. C. Mitchell, J. M. Weetman, R. J. Taylor, and T. P. Kee, Tetrahedron: Asymmetry, 1995,6,2039. Z. Li and C. Zhu, Main Group Met. Chem., 1995,18,669. A. Bongini, M. Panuzio, E. Bandini, G. Martelli, and G. Spunta, Synlett., 1995, 461. E. Bandini, G. Martelli, G. Spunta, and M. Panuzio, Tetrahedron:Asymmetry, 1995, 6,2127. T. Yokomatsu, K. Suemune, T. Yamagishi, and S . Shibuya, Synlett., 1995,847. E. Zymanczuk-Duda, B. Lejczak, P. Kafarski, J. Grimaud, and P. Fischer, Tetrahedron, 1995,51,11809. C. Meier, W.H. G. Laux, and J. W . Bats, Liebigs Ann. Chem., 1995, 1963. C . Meier and W.H. G. Laux, Tetrahedron, 1996,52,589. M. Drescher, F.Hammerschmidt, and H. Kaehlig, Synthesis, 1995, 1267, G. Eidenhammer and F. Hammerschmidt, Synthesis, 1996,748. T. Yokomatsu, N. Nakabayashi, K. Matsumoto, ans S . Shibuya, Tetrahedron: Asymmetry, 1995,6,3055. B. Principato, M. Maffei, C. Siv, G. Buono, and G. Peiffer, Tetrahedron, 1996, 52, 2087. E. L. Muller, A. M. Modro, and T. A. Modro, Bull. SOC.Chim. Fr., 1994,131,959. P. Page, C. Blonski, and J. P M , Tetrahedron Lett., 1995,36,8027. P. V. P. Pragnacharyula and E. Abushanab, Tetrahedron Lett., 1995,36,5507. W . Y. Lau, L. Zhang, J. Wang, D. Cheng, and K. Zhao, TetrahedronLett., 1996,37, 4297. G. D. Duncan, Z-M. Li, A, B. Khare, and C.E. McKenna, J. Org. Chem., 1995,60, 7080. S . V. Serves, D. N. Sotiropoulos, and P. V. Ioannou, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,107,27. M . V. Khalmukhamedova, T. A. Agzamov, and A. B. Alovitdinov, Russ. J. Org. Chem.. 1995,31,360. R. Ruel. J-P.Bouvier, and R. N. Young, J. Org. Chem., 1995,60,5209. G. R. Kieczykowski,R. B. Jobson, D. G. Melillo, D. F. Reinhold, V. J. Grenda, and I. Shinkai, J. Org. Chem., 1995,60,8310. N. J. Barnes, M. A. Probert, and R. H. Whitman, J. Chem. SOC.Perkin Trans.1, 1996,431. S. V. Biryukov, M. F. Rostovskaya, and V. I. Vysotskii, Russ. J. Gen. Chem., 1995, 65,536. J . Nieschalk and D. O’Hagan, J. Chem. SOC.,Chem. Commun. 1995,719. J. Nieschalk, A. S. Batsanov, D. OHagan, and J. A. K. Howard, Tetrahedron, 1996, 52, 165. D. Y. Kim, M. S. Kong, and D. Y. Rhie, Synth. Commun., 1995,25,2865. D. Y. Kim, M. S.Kong, and T. H. Kim,Synth. Commun., 1996,26,2487. B. Corbel, I. L’Hostis-Kervella,and J-P. Haelters, Synrh. Commun., 1996,262561. P. Coutrot, C. Grison, M. Lachgar, and A. Ghribi, Bull. SOC.Chim. Fr., 1995,132, 925. T. P.Lequeux and J. M. Percy, J. Chem. SOC.,Chem. Commm., 1995,2111. K. Blades, T. P. Lequeux, and J. M. Percy, J. Chem. Soc., Chem. Cummun, 1996, 1457. R. Neidlein and H. Feistauer, Helv. Chim. Acta, 1996,79,895. Y. Zanella, S. Beit&Verrando, R. Dizikre, and P. Savignac, J. Chem. SOC.,Perkin Trans. I , 1995,2835.

4: Quinquevalent Phosphorus A c i h

165

164.

H. Al-Badri, E. About-Jaudet, J-C. Combret, and N. Collignon, Synthesis, 1995,

165.

B. A. Baimashov, S. V. Grigor’ev, N. A. Polezhaeva, and E. N. Klimovitskii, Russ. J. Gen. Chem., 1995,6S, 464. C-W. Li, J. E. Hong, and D. Y. Oh, J. Org. Chem., 1995,60,7027. B. A. Kashemirov, J-Y. Ju, R. Bau, and C. E. McKenna, J. Am. Chem. Soc., 1995,

1401. 166. 167.

117,7285. 168.

B. A. Kashemirov, M. Fujimoto, and C. E. McKenna, Tetrahedron Lett., 1995,36,

169.

H-J. Zhou, Y-Q. Zhang, Y-G. Li, J-L. Wang, X-L. Liu, F-M. Miao, S.G. Yang, XC. Jiang, R. Feng, and Z-X. Yan, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,

9437. 102, 185.

T. P.Lequeux and J. M. Percy, Synlett., 1995,361. C. Yuan and C. Li, Phosphorus, Su&, Silicon, Relat. Elem., 1995,103, 133. D. G. Brawn, E. J. Velthuisen, J. C. Commerford, R. G. Brisbois, and T. R. Hoye, J. Org. Chem., 1996,61,2540. 173. Y. Okada, T. Minami, M. Miyamoto, T. Otaguro, S. Sawasaki, and J. Ichikawa, Heteroat. Chem., 1995,6, 195. 174. T. Gajda, M. Nowalinski, S. Zawedzki, and A. Zwienak, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995?105, 45. 175. A. S. Demir, C. Tanyeli, 0. Sesenoglu,S. Demic, and 0. 0. Evin, Tetrahedron Lett.,

170. 171. 172.

1996,37,407. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187.

L. Maier and P. J. Diel, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 107,245. S . Failla and P.Finocchiaro, Phosphorus, Sulfur.Silicon. Relat. Elem 1995,107,79. C . Hubert, A. Munoz, B. Garrigues, and J-L. Luche, J. Org. Chem., 1995,60,1488. J. Barycki, R. Gancan, M. Milewska, and R. Tyka, Phosphorus, Sulfur, Silicon. Relat, Elem., 1995,105, 117. H. Groeger and J. Martens, Synth. Commun., 1996,26,1903. K . J. Koeller, N. P. Rath, and C. D. Spilling, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,103, 171. A. B. Smith, K. M. Yager, and C. M. Taylor, J. Am. Chem. Soc., 1995,117,10879. M. Mikolajczyk, P. Lyzwa, J. Drabowitz, M. W. Wieczorek, and J. Blaszczyk, J. Chem. SOC.Chem. Commun., 1996,1503. R. Gancan, Tetrahedron, 1995,51,10627. R. Gancarz, I. Gancan, and U. Walkowiak, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,104,45. T. Bailly and R. Burgada, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,101, 131. S . Failla and P. Finocchiaro, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995, 105, 195.

188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200.

S-K.Chung and D-H. Kang, Tetrahedron:Asymmetry, 1996,7,21. B. Boduszek, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,104,63. M. Hatam and J. Martens, Synth. Commun., 1995,255,2553. M. Borloo, X-Y. Jiao, H. Wbjtowicz, P. Rajan, C. Verbruggen, K. Augustyns, and A. Haemers, Synthesis, 1995, 1074. M. Cowart, E. A. Kowaluk, K. L. Kohlhaas, K. M. Alexander, and J. F. Kerwin, Bioorg. Med. Chem. Lett., 1996,6,999. C. Mawy, T.Gharbaoui, J. Royer, and H-P. Husson, J. Org. Chem., 1996,61,3687. E. Oehler and S. Kanzlen, Monatsh. Chem., 1996,127,177. H. Krawczyk, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,101,221. M. Seki and K. Matsumoto, Synthesis, 1996,580. A. Mucha, P. Kafarski, F. Plenat, and H-J. Cristau, Phosphorus, Suvur, Silicon, Relat. Elem., 1995, 105, 187. D. Kantoci, J. K. Demike, and W. J. Wechter, Synth. Commun., 1996,26,2037. U. Schmidt, G. Oehme. and H. Krause, Synth. Commun., 1996,26777. N. Langlois, A. Rojas-Rousseau, and 0. Decavallas, Tetrahedr0n:Asymmetry.1996, 7, 1095.

166

Organophosphorus Chemistry

201.

A. Belyaev, M. Borloo, K. Augustyns, A-M. Lambeir, I. De Meester, S. Sharp& N. Blaton, 0. M. Peeters, C. De. Ranter, and A. Haemers. Tetrahedron Lett., 1995, 36,3755.

202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218.

219. 220. 221. 222. 223. 224.

A. Studer and D. Seebach, Heterocycles, 1995,40,357. A. Ryglowski, R. Lazaro, M. L. Roumestant, and Ph. Viallefont, Synth. Commun., 1996,26,1739. A. Bonghi, R. Camerini, and M. Panunzio, Tetrahedron;Asymmetry, 1996, 7, 1467. M. Kitamura, M. Tokunaga, T. Pham, W. D. Lubell, and R. Noyori, Tetrahedron Lett., 1995,36,5769. B. B. Lohray, D. K.Maji, and E. Nandaran, Indian J, Chem., Section B, 1995, 34, 1023. A. Heisler, C. Rabiller, and G. Haegele, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,101,273. M. Ben-Bari, G. Dewynter, C. Aymand, T. Jei, and J-L. Montero, Phosphorus, Sulfur.Silicon, Relat. Elem., 1995, 105, 129. K. Tanaka, H. Iwabuchi, and H. Sawanishi, Tetrahedron; Asymmetry, 1995,6,227 1. L. Cipolla, L. Lay, F. Nicotra, L. Panza, and G. Russo, J. Chem. Soc.,Chem. Commun.. 1995,1993. K. Baczko, W-Q. Liu, B. P. Roques, and C. Garbay-Jaureguiberry, Tetrahedron, 1996,52,2021. D. Solas, R. L. Hale, and D. V. Patel, J. Org. Chem., 1996,61, 1537. M. S. Smyth and T.R. Burke, Org. Prep. Proced. Int., 1996,28,77. W .Cen and Y . Shen, J. Fluorine Chem., 1995,72, 107. W . Huang and C. Yuan, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,106,163. A. A. Prishchenko, M. V. Livantsov, K-L. Lorents, E. V. Grigor’ev, and Yu. N. Luzikov, Russ. J. Gen. Chem., 1994,64,1408.

A. A. Prishchenko, K-L.Lorents, M. V. Livantsov, S. V. Min’ko, E. V. Grigor’ev, and Yu. N. Luzikov, Russ. J. Gen. Chem., 1994,64,1409. W . Froestl, S. J. Mickel, G. von Sprecher, P. J. Diel, R. G. Hall, L. Maier, D. Strub, V. Melillo, P. A. Baumann, R. Bernasconi, C. Gentsch, K. Hauser, J. Jaekel, G. Karlsson, K.Klebs, L. MPitre, C. Marescaux, M. F. Pozza, M. Schmutz, M. W. Steinmann, H. van Riezen, A. Vassout, C. Mondadori, H-R. Olpe, P. C. Waldmeier, and H. Bittiger, J. Med Chem., 1995,38,3313. W . Froestl, S. J. Mickel, R. G. Hall, G. von Sprecher, D. Strub, P. A. Baumann, F. Brugger, C. Gentsch, J. Jaekel, H-R. Olpe, G. Rihs, A. Vassout, P. C. Waldmeier, and H. Bittiger, J. Med. Chem., 1995,38,3297. E. K.Baylis, Tetrahedron Lett., 1995,36,9385,9389. M. E. Tanner, S. Vaganay, J. van Heijenoort, and D. Blanot, J. Org. Chem., 1996, 61, 1756. S. Chen and J. K.Coward,TetrahedronLett., 1996,37,4335. A. Mucha, R.Tyka, and P. Kafarski, Heterout. Chem., 1995,6,433. C. Yuan, S. Chen, R.Xie, and H. Feng, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,106,115.

225. 226. 227. 228. 229. 230. 231.

C . Yuan and C . Li, Synthesis, 1996,507. D. V. Patel, K. Rielly-Gauvin, D. E.Ryono, C. A. Free, W.L. Roger, S.A. Smith, J. M. DeForrest, R. S. Oehl, and E. W .Petrillo, J. Med. Chem., 1995,38,4557. C . C. Tang, F. P. Ma, K. Zhang, Z. J. He, and Y. C. Jin, Heterout. Chem., 1995,6, 413. S. R. Piettre, Tetrahedron Lett., 1996,37,4707. S . R. Piettre and P. Raboisson, Tetrahedron Lett., 1996,37,2229. A. Lopusinski, L. Luczak, and J. Michalski, Heterout. Chem., 1995,6,365. L.Jaeger, N. Inguimbert, M.Taillefer, and H. J. Cristau, Synth. Commun.,1995,25, 2857.

232.

M. de F. Fernandez, C. P. Vlaar, H. Fan, Y-H.Liu, F. R. Fronczek, and R. P. Hammer, J. Org. Chem., 1995,60,7390.

4: Quinquevalent Phosphorus Acids

233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268.

167

0. I. Kolodiazhynyi, E. V. Grishkun, S. V. Galushko, and 0. R. Golovatyi, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,103, 183. J. Mitjaville, A.-M. Caminade, and J-P. Majoral, Synthesis, 1995,952. Yu. I. Blokhin, D. V. Gusev, V. K. Belsky, A. I. Stash, and E. I. Nifantyev, Phosphorus, Sulfm, Silicon, Relat. Elem., 1995, 102, 143. Yu. G. Trishin, B. F. Mingazova, and I. V. Konovalova, Russ. J. Gen. Chem., 1995, 65, 142. Yu. G. Trishin, M. V. Vorob’ev, and V. I. Namestnikov, Russ. J. Gen. Chem., 1995, 65,144. V. I. Vysotskii and A. G. Vilitkevich, Russ. J. Gen. Chem., 1995,65, 706. G. Keglevich, L.Toke, Z. Bocskei, D. Menyhard, and L. D. Quin, Heteroat. Chem., 1995,6,593. M. K. Tasz, A. Gamliel, 0. P. Rodriguez, T. M. Lane, S. E. Cremer, and D. W. Bennett, J. Org. Chem., 1995,60,6281. M. J. Gallagher, M. G. Ranasinghe, and I. D. Jenkins, J. Org. Chem., 1996, 61, 436. H. Al-Badri, E. About-Jaudet, and N. Collignon, J. Chem. Soc., Perkin Trans.1, 1996,931. S-Y. Wu and J. E. Casida, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,102, 177. C . Ma, Z. Lu, andY. Ma, J. Chem. SOC.,Perkin Trans. 1, 1995,2683. A. B. Akacha, M. Boukraa, S. Barkallah, M. T. Boisdon, H. Zantour, and B. Baccar, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,102, 1. V. N. Chistokletov, E. D. Maiorova, and A. Yu. Platonov, Russ. J. Gen. Chem., 1995,65,293. V. A. Loskutov and V. I. Mamatyuk, Russ. Chem. Bull., 1995,44,137. M. Boukraa, N. Ayed, A. Ben Akacha, H. Zantour, and B. Baccar, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,105, 17. A. I. Golubin, B. V. Timokhin, and S . V. Zinchenko, Russ. J. Gen. Chem., 1995,65, 291. M. Saady, L. Lebeau, and C. Mioskowski, Synlett., 1995,643. J-M. Campagne, J. Costa, and P. Jouin, J. Org. Chem., 1995,60,5214. M. Skwarczynski and P. Kafarski, Synth. Commun., 1995,25,3565. C. Patois, P. Savignac, E. About-Jaudet, and N. Collignon, Org. Synth., 1996, 73, 152. C. J. Salomon and E. Breuer, Tetrahedron Lett., 1995,36,6759. J. Vepsiiliiinen,H. Nupponen, and E. Pohjale, Tetrahedron Lett., 1996,37,3533. R . Hirschmann, K. M. Yager, C. M. Taylor, W. Moore, P. A. Sprengeler, J. Witherington, B. W. Phillips, and A. B. Smith, J. Am. Chem. Soc., 1995, 117, 6370. A. Piencar, A. M. Modro, and T. A. Modro, Heteroat. Chem.,1996,7,177. S . E. Denmark and C-T. Chen, J. Am. Chem. Soc., 1995,117, 11879. M. Kranz and S.E. Denmark, J. Org. Chem., 1995,60,5867. N. N. Demik, M. M. Kabachnik, Z. S.Novikova, and I. P. Beletskaya, Russ. J. Org. Chem., 1995,31,57. I. C. Baldwin, R. P. Beckett, and J. M. J. Williams, Synthesis, 1996,34. T.Taapken and S . Blechert, Tetrahedron Lett., 1995,36,6659. E. Montoneri, P. Savarino, F. Adani, and G. R i m , Phosphorw, Sulfur, Silicon, Relat. Elem., 1995, 106,37. Zh. E. Botata, L. I. Deiko, G. A. Berkova, T. K. Kostina, G. M. Baranov, and V. M. Berestovitskaya, Russ. J. Gen. Chem., 1995,65,958. Y .Shen and M. Qi, J. Chem. Rex ( S ) . 1996,328. D. V. Griffiths, P.A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. Res. (S), 1996,176; (M)0901. D. V. Griffiths, P. A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. SOC.Perkin Trans. I , 1996,555. S . R. Piettre, C. Girol, and C. G. Schelcher, TetrahedronLett., 1996,37,4711.

168

Organophosphorus Chemktry

269. J. E. Hong, W. S. Shin, W. B. Jang, and D. Y. Oh, J. Org. Chem., 1996,61,2199. 270. D.Fouqui, E.About-Jaudet, and N. Collignon, Synth. Commun., 1995,25,3443. 271. D.Fouque, H.Al-Badri, E. About-Jaudet, and N. Collignon, Bull. Soc. Chim. Fr., 1994,131,992. 272. M. J. Mphahlele and T. A. Modro, J. Org. Chem., 1995,60,8236. 273. M. J. Mphahlele, A. Pienaar, and T. A. Modro, J. Chem. Soc. Perkin Trans.2, 1996, 1455. 274. K. Tanaka, Y.Ohta, and K. Fuji, J. Org. Chem., 1995,60,8036. 275. S. E.Denmark and J-H. Kim, J. Org. Chem., 1995,60,7535. 276. T. Yokomatsu, T. Yamagishi, and S . Shibuya, Synlett., 1995,1035. 277. M. Gulea-Purcarescu, E. About-Jaudet, and N. Collignon, Tetrahedron Lett.. 1995, 36,6635. 278. S . E.Denmark and P. C. Miller, TetrahedronLett., 1995,36,6631. 279. T. Schuster and S . A. Evans, Phosphorus, Sulfur,Silicon, Relat. Elem.. 1995, 103, 259. 280. C. K. McClure and K.B. Hansen, Tetrahedron Lett., 1996,37,2149. 281. C. K.McClure, K. J. Henog, and M. D. Bruch, Tetrahedron Lett., 1996,37,2153. 282. V. V. Ovchinnikov, F. Kh. Karataeva, and R. A. Cherkasov, Russ. J. Gen. Chem., 1995,65,361. 283. J. H. Byers, J. G. Thissell, and M. A. Thomas, Tetrahedron Lett., 1995,36,6403. 284. P. Balczewski, Phosphorus, Sulfur,Silicon, Relat. Elem.. 1995,104,113. 285. T. Kawashima, H. Iwanaga, and R . Okazaki, Heteroat. Chem., 1995,6,235. 286. M. Yu.Dmitrichenko, V. G. Rozinov, and V. I. Donskikh, Russ. J. Gen. Chem.. 1995,65,374. 287. G. Keglevich, K.UjszBszy, G. S. Quin, and L. D. Quin, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995,106,155. 288. M. J. P.Harger and B. T. Hurman, J. Chem. Soc., Chem. Commun., 1995,1701. 289. M.J. P.Harger and R. Sreedharan-Menon,J. Chem. Soc. Chem.Commun.,1996,867. 290. M. J. P.Harger, J. Chem. Res. ( S ) , 1996,110. 291. S. Olagnon-Bourgeot, F. Chastrette, and D. Wilhelm, Magn. Reson. Chem., 1995, 33,971. 292. A. Brueck, W.Kuchen, and W. Peters, Phosphorus, Sulfur, Silicon. Relat. Elem., 1995,107,129. 293. G. Grossmann, G.Ohms,K. Krueger, and G. Jeschke, Phosphorus, Sulfur,Silicon, Relat. Elem., 1995,107,57. 294. T. A. Zyablikova, B. I. Buzykin, and M. P. Sokolov, Russ. J. Gen. Chem., 1995,65, 227. 295. Z . Glowacki, M,Hoffmann, and J. Rachon, Phosphorus, Sulfur, Silicon, Relat. EZem., 1995,104,21. 296. E. Zymanzyk-Duda, M. Skwarezynski, B. Lejczak, and P . Kafarski, Tetrahedron; Asymmetry, 1996,7,1277. 297. D. G . Genov and J. C. Tebby, J. Org. Chem., 1996,61,2454. 298. S . Bourne, A. M. Modro, and T. A. Modro, Phosphorus, Sulfur, Silicon. Relat. Elem.. 1995,102,83. 299. T. C. Sanders, G.B. Hammond, J. A. Golen, and P . G. Williard, Actu Crystallogr., Section C., 1996,52,667. 300. T.M. Lane, S. M. Levson, M. K. Tasz, S. E. Cremer, M. S. Hussain, and Mazharul-Haque, Heteroat. Chem., 1996,7,9. 301. T. M.Lane, 0. P.Rodriguez, S. E. Cremer, and D. W . Bennett, Phosphorus. Suvur, Silicon, Relat. Elem., 1995,103,63. 302. T. M. Lane, 0.P. Rodriguez, M. K. Tasz, A. G . Sommese, S. E. Cremer, D. Bennett, and P . Fanwick, Phosphorus, Sulfur,Silicon, Relat.Elem., 1995,102,115. 303. A. S. Dokuchaev, B. I. Buzykin, M. P.Sokolov, and V. F. Sopin, Russ. Chem. Bull.. 1994,43,1180. 304. C. S. Browning, T. E. Burrow, D. H. Farrar, and A. J. Lough, Acta Crystallogr., Sect. C,1996,52,652.

4: Quinquevalent Phosphorus Acids

305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329.

169

M. W. Wieczorek, J. Blaszazyk, M. J. Potrzebowski, A. Skowronska, and R. Dembinski, Phosphorus, Sulfur. Silicon, Relat. Elem., 1995,102, 15. N. K. Skvortsov, S. V. Toldov, A. I. Stash, and V. K. Bel’skii, Russ. J. Gen. Chem., 1996,66,717. S . Z. Zhu and X.L. Jin, J. Fluorine Chem., 1995,72, 19. A. A. Kadyrov, I. Neda, T. Kankorat, A. Fischer, P. G. Jones, and R. Schmutzler, J. Fluorine Chem., 1995,72,29. I. Neda, H-J. Plinta, A. Fischer, P. G. Jones, and R. Schmutzler, J. Fluorine Chem., 1995,72,9. F. Carre, C. Chuit, R. J. P. Corriu, P. Monforte, N. K. Nayyar, and C. Reye, J. Organomet. Chem., 1995,499,147. N. A. Alexandrova, I. A. Litvinov, 0. N. Kataeva, V. A. Naumov, V. S. Reznik, R. R. Shagidullin, and Yu.S . Shvetsov, Izvest. Akad. Nauk., Ser. fib. Nauk,, 1995, 1125; Chem. Abstr., 1996,124, 56084. B. Kramer, E. Niecke, M. Nieger, and R. W. Reed, J. Chem. SOC.,Chem.Commun., 1996,513. W. Henderson, A. G. Oliver and A. J. Downard, Polyhedron, 1996,15,1165. M. J. Pilkington, A. M. Z. Slawin, D. J. Williams, and J. D. Woollins, Main Group Chem., 1995,1,145. L. Liu, R. Zhuo, and R. Chen, Phosphorus, Sulful; Silicon, Relat. Elem., 1995, 107, 107. H. Beckmann, G. Ohms, G. Grossmann, K. Krueger, K. Klostermann, and V. Kaiser, Heteroat. Chem., 1996,7, 111. J. Blaszczyk, M. W.Wieczorek, A. Okruszek, A. Sierzchala, A. Kobylanska, and W.J. Stec, J. Chem. Crystallograph.,l996,26,33. E. E. Nifant’ev, D. A. Predvoditelev, M. A. Malenkovskaya, A. R. Bekker, N. S. Magomedova, and V. K. Bel’skii, Russ. J. Gen. Chem.. 1995,65,328. S . M. Naidu, M. Krishnaiah, and K. Sivakumar, Actu. Crystallogr., Sect. C,1996, 52, 1556. G. Grossmann, H. Beckmann, 0. Rademacher, K. Krueger, and G. Ohms,J. Chem. Soc., Dalton Trans., 1995,2797. M. R. St.J. Foreman, A. M. Z. Slawin, and J. D. Woollens, J. Chem. Soc., Chem. Commun., 1995,2217. E. E. Nifant’ev, T. S.Kukhareva, V. I. Dyachenko, A. F. Kolomietz, V. K. Bel’skii, and L. K. Vasyanina, Russ. Chem. Bull., 1995,44,1748. M. K. Tasz, S. E. Cremer, and P. E. Fanwick, Phosphorus, Suyur, Silicon, Relat. Elem., 1995,104,223. M. K. Tasz, S. E. Cremer, and P. E. Fanwick, Phosphorus, Sulfur, Silicon, Relat. Elem., 1995,103, 137. H. Jancke, B. Costisella, and K. Jancke, Fresenius’ J. Anal. Chem., 1995,352,496. C. D. Reddy, M. S. Reddy, C. V. N. Rao, C. N. Raju, @. Das, and G. S . Reddy, Indian J, Heterocycl. Chem., 1995,S, 49. R. Koch and E. Anders, J. Org. Chem.. 1995,60,5861. A. Rauk, I. F. Shishkov, L. V. Vilkov, K. F. Koehler, and R. G. Kostyanovsky, J. Am. Chem. SOC.,1995,117,7180. W. G. Bentrude in ‘Conformational Behaviour in Six-Membered Rings’ ed. E. Juaristi, VCH, New York, 1995,245-293.

5 Nucleotides and Nucleic Acids BYJANE A. GRASBY AND DAVID M.WILLIAMS

1

Introduction

There continues to be interest in nucleotide antiviral agents and a number of novel prodrug approaches have been developed to address their biodelivery. Several novel base modified and sugar-modifiednucleotides and oligonucleotides have been described, but the main area of interest has been concerned with designing modified internucleotide linkages. These include nucleoside phosphonates and analogues thereof, in addition to a large number of oligonucleotides with modified internucleotide linkages. The potential therapeutic applications of the latter have provided the impetus for approaches aimed at the stereocontrolled synthesis of modified, chiral internucleotide linkages, whilst the design of these has also concentrated on the need for drug stability in vivo and drug delivery. In addition, a number of publications have investigated methodology which may be applied to the large scale synthesis of modified oligonucleotides. The growing interest in the use of synthetic RNA has also given rise to improvements in synthetic methodology, particularly with respect to its large scale synthesis. The use of H-phosphonate chemistry and its applications in the synthesis of modified oligonucleotides has also gained momentum. One of the most rapidly developing areas continues to be that of mass spectrometry using the MALDI technique. Several novel applications related to oligonucleotidecharacterisation and analysis have been made using this technique.

2

Mononucleotides

2.1 Nucleoside Acyclic Phosphates 2.1.1 Mononudeoside Phosphate Derivatives. - There continues to be an interest in the delivery of nucleotide prodrugs as lipophilic triester derivatives, which are hydrolysed intracellularly to their corresponding active monophosphates. The nucleoside analogue 2’,3’-didehydro-2’,3’-dideoxythymidine(d4T) once phosphorylated displays comparable anti-HIV activity to AZT whilst exhibiting a much reduced cytotoxicity. Since d4T is a poor substrate for cellular thymidine kinase several prodrugs have appeared recently which do not require activation. McGuigan and co-workers have synthesised the phosphoramidate (1) which is 2-5 times more potent than d4T at inhibiting HIV replication and in particular is 300-500 times more potent than the parent nucleoside in thymidine kinase deficient (TK-)cells.’ A series of related compounds (2)* have now been prepared by the same group. The mechanism of action of d4T has been confirmed 170

5: Nucleotides and Nucleic A c i h

R1--O-KF'O~T

171

0 II

-

I H-C-~2

I

OGC'OMe

OSC'OMe

0

Ho-i,owT I1

H-C-Me I I

OGc'OH

(3)

CI'

R2 = Me, Pr', Bu', Bz, or MeS-

in TK- cells, whereby following administration of tritium-labelled d4T prodrug (l),the mono, di and triphosphate of labelled d4T is detected. In addition the major metabolite (3) was also identified and may likewise be involved in the observed anti-HIV activity. The bis(S-acetyl-2-thioethy1)phosphate triester of d4T (4) has also been prepared3 and displayed enhanced anti-HW activity relative to the parent nucleoside in both TK+ and TK- cell lines. All the aforementioned d4T prodrugs require cellular activation to d4T monophosphate. In contrast, the novel nucleoside-S-O-(4H-1,3,2-benzodioxaphosphinin-2-oxides) (5) of both 3'-deoxythymidine (ddT) and d4T have been designed4 as prodrugs which do not require an intracellular enzymatic activation step (see volume 27 in this series). They are prepared in 70-85% yield by reaction of the respective free

MeOy\ H OSc'OMe

Organophosphorus Chemistry

172

nucleosides with the chlorophosphite (6), followed by oxidation with tertbutylhydroperoxide. The prodrugs possess partition coefficients (1-0ctanoY phosphate buffer pH 6.5) between 8 and 50 fold higher than the respective parent nucleosides and presumably exhibit better membrane permeability. At pH 7, spontaneous cleavage to (7)followed by elimination of the 2-hydroxybenzyl alcohol affords the nucleoside monophosphate. Half-lives vary from about 10 minutes for X=N02 to 9 hours for X=OMe. The phosphoramidate prodrug of 2’,3’-dideox~-3’-thiacytidine(3TC) (8) has also been synthesi~ed.~ It displayed much poorer inhibition of HIV-1 and HIV-2 replication relative to that of 3TC, whilst its activity was equivalent to that of the free nucleoside in inhibiting hepatitis B. An alternative approach to the delivery of the monophosphate prodrugs of nucleoside analogues uses the strategy shown in Scheme 1.6 In this scheme compounds (9) possessing the crown ether will bind sodium ions resulting in a neutral lipophilic complex which is capable of active cellular uptake by virtue of the associated sodium ions. Intracellular cleavage produces the nucleoside monophosphate. The compounds were made by reacting the phenolic crown ether with phosphoryl chloride followed by addition of the free nucleoside. Whilst the AZT analogue displayed a lower anti-HIV activity than AZT itself, the ddU analogue was 11 times more active than the free nucleoside, which is normally a poor substrate for cellular kinases. 0

0

-OH

0 II

-0-P-ONuc

Lipophilic

Hydrophilic

Nuc = 5’-nucleoside Scheme 1

0 O-P-0-NUC

g

b

(10) X = Br, CI, I or OTs

5: Nucleotides and Nucleic Aci&

173

The phosphoramidate derivatives of 2’-deoxy-5-fluorouridine (10) have been designed as prodrugs of the potent anticancer agent FdUMP.7 A series of derivatives were prepared by reaction of 3’-O-Tbdms-FdU with the appropriate phosphoramido chloridate. The perhydrooxazino substituent was designed to increase lipophilicity and hence cell permeability. The phosphoramidate monoester would then be produced by enamine expulsion or via hydrolysis and elimination from the resulting aldehyde. In addition, the irreversible, active site alkylation and hence inhibition of thymidylate synthase, was anticipated as shown in Scheme 2, pathway A. However it was concluded that the analogues were acting as FdUMP prodrugs rather than as alkylating agents (pathway B). X

f:

0 *N-!-0-FdU I 1 M l p l M pO O

’-N-P-O-FdU

Y

h

e

A-

0 II

-0- P- 0- FdU I

Me O-

0-

J

E = nucleophile in thymidylate synthase active site

Me O-

Scheme 2

A series of 5’-phosphatidyl derivatives (11) of the potent anti tumour agent l-(2-C-cyano-2-deoxy-~-D-arabino-pentofuranosyl)c~osine(CNDAC) have been prepared.* Since CNDAC is sensitive to the normal chemical phosphorylation conditions, the compounds were prepared by phospholipase catalysed phosphorylation of CNDAC using the respective phosphatidyl choline derivative

+ II

I 0-

HO (1 1) R = Myristoyl palmitoyl, stearoyl,

oleolyl, linoleoyl

174

Organophosphorus Chemistry ROT

k?

0-Y-ONUC

RO

-0

(13)

(12). A series of phospholipid conjugates of general structure (13) and (14) of

AZT and 3'-deoxyadenosine (cordycepin) have been synthesised from the corresponding phosphoramidites (15) and (16).9 It is envisaged that they will act as prodrugs of the parent nucleoside monophosphates which possess enhanced membrane permeability. A series of photo reactive and radiolabelled CMP-activated sialic acids have been prepared (17),l0 all of which were found to be substrates for a-2,60

0I

0

R'= N 3 e E e ! N H - ,

-

HO

N3-@-NH-.

N3

N3b!-NHCH2C-

!?

OH OH (1 7)

3H

R2 = OH or Ac

0 II

-0-P-0

-0-P-0

HO OH (18)

0

HO OH (19)

5: Nucleotides and Nucleic Acids

175

sialyltransferase. The carbocyclic aminoimidazole carboxamide ribonucleotide (C-AICAR) (lS), an important nucleoside in the biosynthesis of purine nucleosides, and (19) have been prepared.” The analogue (20) has been designed as a hapten for the generation of catalytic antibodies with phosphodiesterase activity.l 2 The compound was synthesised by reaction of (21) with the phosphate diester (22) in the presence of the activating agent triisopropylbenzene sulfonyl chloride.

0 II O X C N

0 % 0 RO’

?

(20) R = - - P - O - N C N - B z I (21) R - H

H

0-

The conformationally-restrained NAD precursors have been prepared’ in which the carboxamide group has the syn (23) or anti (24) conformation with respect to the sugar moiety. Attempts to prepare the corresponding N A D analogues from these derivatives by reaction with 2’,3’-O-isopropylidineprotected adenosine 5’-methylene bisphosphonate were unsuccessful using either DCC or carbonyl diimidazole (CDI) due to the instability of the glycosidic linkages of the analogues.

-0

HO

OH

HO

OH

The sulfamoylated AZT analogue (25) has been prepared as a membrane permeable analogue of AZT triph~sphate.’~ The sulfonylating agent (26) was prepared from diethyl hydroxymethyl phosphonate and chlorosulfonyl isocyanate. Compound (25) was a poor inhibitor of HIV reverse transcriptase but exhibited some anticancer activity. A number of sulfur protecting groups for phosphorothioate diesters (27)which are suitable for the large scale synthesis of phosphorothioate-containingDNA by

176

Organophosphorus Chemistry

0

0

II

II

0

0 0 I1 I1 (EtO)2-PCH2O-C-NH-S-

I1

HO-P-CH2-O-C-NH-S-05-AZT I II OH 0

0 II

::

CI

the phosphotriester approach have been examined.l5 The diesters were prepared in good yields (67-92%) by conversion of the protected nucleoside 3-H-phosphonate to the corresponding silylphosphite with trimethylsilyl chloride, followed by reaction with (28), (29) or (30). The diesters (27) were coupled with 3’-0acetylthymidinein the presence of mesitylene sulfonyl chloride and 3-nitrotriazole and then deprotected to the corresponding dimers. The cyanoethyl group was found to be the most suitable for phosphorothioate synthesis by the phosphotriester method.

“”” 0,

,o-

O/P\SR

(27) Px phenylxanthyl 5

NQ-chs / \

0

I

O+O

The pH dependent chemical hydrolyses of the phosphorothioate analogues 2’-, 3’- and 5’-UMPShave been investigated.16 Between pH 2 and 5 dethiophosphorylation is between 200 and 300 times faster than dephosphorylation due to the higher stability of the intermediate thiometaphosphate compared to the metaphosphate anion. At pH values less than 1, no migration of the thiophosphoryl group takes place but rather, desulfurisation occurs. There is a growing interest in developing the synthetic methodology for nucleoside H-phosphonates and the application of this chemistry to the synthesis of nucleotides and oligonucleotides. A good review of this literature has appeared.l7 A new route to nucleoside 3’-H-phosphonates involves reacting a suitably protected nucleoside with phosphonic acid using bis(trichloromethy1)carbonate (triphosgene) as the activating agent.l 8 The method allows reasonably good yields of H-phosphonates of both 2‘-deoxy- and 2’-O-methylribonucleosides(31)

5: Nucleotides and Nucleic Acidr

177

DMToY 0,

P-H

o’/ ‘0(31) B = T, U, N4-benzoyl C,N6-benzoyl A, N2-isobutyryl G R = H or OMe

and offers advantages due to the ease of handling and stability of triphosgene. NMR evidence suggests the intermediacy of bisphosphonic acid. The nucleoside 3’-H-phosphonothioates (32) have been prepared following activation of the corresponding nucleoside 3’-H-phosphonates with pivaloyl chloride to give the mixed anhydride (33) and subsequent reaction with l,l, 1,3,3,3-hexamethyldisilathiane (HMDTS). The HMDTS acts as both a silylating agent and thiating agent for conversion of (33) to the corresponding silylphosphite which subsequently reacts further to give, after hydrolysis, (32). (33) upon reaction with hydrogen sulfide in dioxan gives the H-phosphonodithioate (34). l9 A related NMR-based mechanistic study of this chemistry has also been published.20The synthesis of 3’-H-phosphonates of several arabinonucleosides (35)as monomers for oligoarabinonucleotidesynthesis has been reported.21 DmtO

6 = N4- ropionyl C, NgEutyryiA, u or N2-phenoxyacetyl G R = H, TWms

P R O=P-H I

S-

(32)

““B I

O=;-H O% (33)

Mmto-l@ DmmY P R

6 = NCisobutyryl C. N6-isovalerylA, N2-phenoxyacetylG or U

The 3’-methylenephosphonte (36) has been prepared via a general route involving Lewis acid catalysed glycosylation of (37) with bis(trimethylsily1)thymine.** An a/p anomeric ratio of 1:6 was obtained in the presence of boron trifluoride.

178

Organophosphorus Chemistry

1,OEt 0GP\

OEt

1,OEt 05 p\ OEt

The nucleotide analogue (38) has been prepared from the difluoromethylene phosphonate precursor (39).23*24 The presence of orthogonal protecting groups at positions 2 and 3 allows the synthesis of the difluoromethylene phosphonates of both ribonucleosides and deoxyribonucleosides.The difluoromethylene phosphonate (40) of the anti-HIV agent FTC has been prepared by glycosylation of bis(trimethylsilyl)-5-fluorocytosine with (41) in the presence of tin (1V)~hloride.~~

0 I1 (Et0)2PCF2

BzO

OBz

(39)

0 II

( EtO), PCF2

The phosphonates (42) and (43) have been prepared26 by reaction of the respective 3'-ketonucleosides with the lithium salt of diethylphosphite, followed by a variation of the Barton deoxygenation procedure involving the radical catalysed deoxygenation of an intermediate mixed oxalate ester, followed by deprotection. The reaction with diethylphosphite is stereoselective, whilst the radical catalysed deoxygenation affords a P/a (42/43) ratio of about 2: 1. Acyclic nucleoside phosphonates have been shown to display a wide variety of biological activity. A review of the antiviral activity of acyclic nucleoside phosphonates has been published.27

5: Nucleotides and Nucleic Acidr

OH

H

179

R OH

(42) R = H or OTbdms

(43)

Methodology for the synthesis of both enantiomers of the potent antiviral N(phosphonomethoxypropyl) derivatives (44) and (45) of adenine, guanine, 2,6diaminopurine, 6-chloro-2-aminopurine and cytosine have been developed.28The enantiomeric tosylates (46),derived from either D( -)- or L(+)- lactic acid, are reacted with the protected base in the presence of caesium carbonate. Removal of the thp protecting group, followed by reaction of the respective alcohol with diisopropyl t0syloxymethylphosphonate and subsequent deprotection gave the respective PMP enantiomer. The same group has also used one of the two enantiomers of (47) as the precursor for the synthesis of 12 different purine analogues of (R)-and (S)-PMP.29A series of 2’-aminomethyl derivatives of N(phosphonomethoxyethyl) nucleotides (48) have been prepared using the epoxide (49) as the precursor.30

(45) (9-PMP

(44) (R)-PMP

(48) R = CH2NH2,CH2NMe2

n

(46) R = T h p (47) R = CH2P(0)(OPri)2

(49)

i

u0 or CH2NMe3

CH2N

The dioxolane nucleoside phosphonates (50) and (51) have been prepared from (52) by glycosylation under Vorbriiggen condition^.^' They were found to be inactive against HIV-1.

180

Organophosphorus Chemistry

2.2.2 Polynucleoside Monophosphates. - The isodideoxyadenosine containing dinucleotide (53) has been prepared by phosphoramidite chemistry as a potential HIV inhibitor which mimics the DNA terminus obtained by the incorporation of isoddATP by the enzyme. The physical properties of the dinucleotide have been investigated and indicate that it has a similar structure to that of ApA but is much more stable to the action of various phosphodiesterase enzymes. Several dinucleotide analogues have been reported as potential prodrugs of the 5’-monophosphates of biologically active nucleotides. These include the a-hydroxybenzylphosphonatesof AzT32 (also see volume 27 in this series) (54), the benzyl phosphate triesters (55)33 and the Qacyloxybenzyl phosphate triesters (56).% The derivatives (56) were prepared from the bis(diisopropy1amino)phosphoramidite (57), whilst (55) were prepared using chloro(2-cyanoethoxy)N, N-diisopropylphosphine. The compounds are designed to undergo intracellular hydrolysis to the corresponding dinucleoside phosphate diesters which may then be degraded enzymatically to the corresponding nucleoside and monophosphate. All are considerably more lipophilic than AZT and in some cases display a higher anti-HIV activity than the parent nucleoside. The triesters (56) were shown to be degraded to the corresponding diesters by porcine liver carboxypeptidase.

“OV 0,

-o’!-oY3 (53)

HO

R-w~-r 0

n

05-AZT

(55) R = 4-Me, 4-CI, 4-CN, 3-NO2 or H

(56) R = Me, Pr or But R

The kinetics of the chemical hydrolysis of the diastereomeric phosphorothioate diesters of uridyl(3’,5’)uridine (58) have been investigated as a means of interpreting enzymatic reactions involving these analogue^.^' Above pH 9 the phosphorothioates are hydrolysed to the corresponding 2’ and 3‘ thiomonophosphates at comparable rates to that ofUpU and the ‘thio effect’ is negligible. Under neutral and acidic conditions, three competing, pH-dependent reactions occur; desulfurisation, cleavage of the phosphodiester linkage and migration of the phosphorothioate diester linkage.

5: Nucleotides and Nucleic Acia!~

181

x-e-Y

0Y HO

OH

(58) X = 0, Y = S; Rp x = s, Y = 0; sp

Cosstick and co-workers have reported an improved procedure for the synthesis of phosphorothiolatecontaining DNA using Arbuzov chemistry in which the nucleoside disulfides are generated in situ from the corresponding thi0este1-s.~~ Several nucleoside disulfides have been prepared and in particular the regioselectivity of reaction of these with a phosphite has been examined. The disulfide (59) allows the preparation of the desired diribonucleoside phosphorothiolate (60) but the reaction is accompanied by some (2-10%) formation of the pyridyl phosphorothiolate. 0 0

s

I O=P-OMe I

(59)

TbdmsO O - Y YOTbdms

Nine different N7-cyanoborane-2’-deoxyguanosinecontaining dinucleotides of general structure (61)have been prepared using phosphite triester chemistry and the phosphoramidite (62) or 3’-O-acetyl-N7-cyanoborane-Z-deoxyguanosine. Yields between 26 and 52% were obtained. Phosphorus and proton NMR of the dinucleotides indicate that the base analogue causes minimal structural perturbation and should allow Watson-Crick but not Hoogsteen base pairing.

182

Organophosphorus Chemistry

HO

B = A, C, G, or T; B'

=

F>t')

NH2

I

B = 7bG; B' = A, C, G, or T B = B' = 7bG

A number of novel dinucleotide phosphonate and phosphonamidate analogues (63) and (64) incorporating biologically active nucleosides have been prepared.37 The phosphonates were obtained via Arbuzov reaction of trimethylphosphite with the respective bromonucleosides, followed by coupling with the desired nucleoside 3'-hydroxyl group in the presence of trichloromethanesulfonyl chloride as the activating agent. Several of the compounds displayed good antiherpes activity and in particular the phosphonamidites possessing the unnatural methyl D-alaninate moiety displayed less cellular cytotoxicity than the L-amino acid containing analogues.

0: ,OH P O A o ,"),

d (63) R = F orN3 X = 0-, D or L-Me02CCH(Me)NH

(64)

An approach to the stereospecific, solid phase synthesis of methylphosphonates has been developed whereby an appropriately protected, stereochemically pure Rp or Sp Y-(p-nitrophenyl methylphosphonate) ester (65) is coupled to an activated 5'-hydroxyl group of a support-bound n ~ c l e o s i d e .The ~ ~ 5'-hydroxyl group is activated by the addition of a Grignard reagent in pyridine and the release of p-nitrophenol is accompanied by stereospecific internucleotide bond

5: Nucleotides and Nucleic A c i h

183

formation to give the Rp or Sp dinucleoside methylphosphonate (66). Stereospecifities are high; Sp-phosphonate diester gives the Sp dimer in a diastereomeric ratio better than 25:1, whilst the Rp starting material affords the Rp dimer exclusively. The use of high-loaded polyethylene glycol coated polystyrene beads allows the reactions to take place on the surface of the support which avoids problems associated with the otherwise poor diffusion of the Grignard reagent into the pores of a normal CPG support.

DmtoYbz Dmto-P

The nucleosidyl-3’-methylfluoridophosphonates(67) and (68) have been used for the synthesis of the corresponding methylphosphonate (69) and methylphosphonothioate (70) dimers re~pectively.~~ The diastereomers (67) and (68) were prepared by phosphorylation of the corresponding 5’-protected nucleosides with (71)and for the latter mixture (68), separation of the individual diastereomers was possible using silica chromatography. Coupling of (67)and (68) with a 3‘-O-protected nucleoside in the presence of DBU or sodium hydride gave over 95% yield of the respective dimers.

X

II

F

Me- -P ,

F

O--P-X / \Me F

R’-0 (67) X = 0 (68) X = S

I

(69) X = 0 (70)X = S

(71) X = Oor S

184

Organophosphorus Chemistry

A novel route to nucleoside phosphorofluoridate (72) and phosphorofluoridothioate diesters (73) using H-phosphonate chemistry has been described.40 Thus oxidation of a dinucleoside H-phosphonate (74) or phosphonothioate (75) with iodine in the presence of triethylamine trishydrofluoride gives (72) or (73) in 5 or 20 minutes respectively, presumably via the respective intermediate phosphoroiodate diesters.

MmtoYMmtoY 0

:p\=x

O - V MmtO

(72) X = 0 (73) x = s

4

H-P=X I

O Y MmtO (74) (75)

x=0 x =s

A new method for internucleotide bond formation uses a transesterification reaction in pyridine of the aryl nucleoside H-phosphonate diesters (76) with a 5-hydroxyl group of the second nucleosidic component to give the H-phosphonate diester (77).41Since the method does not require the use of pivaloyl chloride or any other activating agent it should expand the synthetic potential of H-phosphonate diesters.

Dmto Y O=P-0 I

cI *cl

H

ci

O='P-H I

0l/OJb'

(76)B = T, AbZ, CbZor Gib BzO

(77)

The novel dinucleotide phosphoramidate (78) has been obtained from the phosphoramidite dimer (79) upon reaction with methoxymethylene ethanolamine in the presence of tetrazole, followed by iodine oxidation in the presence of the same a m i ~ ~ eSince . ~ * the two amino substituents are identical it is envisaged that in aqueous solution, rapid proton transfer between the two phosphoramido moieties will render the molecule achiral at phosphorus.

5: Nucleotides and Nucleic Acidr

185

+-

0,

P-N

OAc

O OAc

V

(79)

2.2 Nucleoside Cyclic Phosphates. - A novel analogue of the secondary messenger cyclic ADP ribose (cADPR) containing the fluorescent nucleoside 1,N6-ethenoadenosine (80) has been prepared from the corresponding NAD analogue using the commercially available, ADP ribosylcyclase from ApZasia c~lifornica.~~ It was shown by NMR to be linked through the N1 position (analogous to the N7 position of adenine). This is the same position of attachment which is observed for the corresponding cyclic guanosine and inosine derivatives which have been prepared by this route. The same method has also allowed the cyclisation of 3'-NADP and 2'-3'-cyclicNADP to give (81) and (82) respectively.44The analogue cADPRP (81) was found to be more effective than cADPR in causing Ca2' release from rat brain microsomes. OH

The cyclic uridylic acid (83) has been synthesised in 40% yield by selfcondensation of the precursor (84) in the presence of isodurene disulfonyldichloride and t e t r a ~ o l e Compound .~~ (84) was obtained by derivatisation of a 5-iodouridine using the Heck reaction to give a 5-(3-hydroxypropyl)uridinewhich was then condensed with S,S-diphenylphosphorodithioate.NMR data showed that (83) is constrained in the anti conformation and possesses a C3'-endo conformation, analogous to that found in A-form RNA. It was suggested that the analogue may be valuable for antisense studies, since when incorporated into an oligonucleotide it might confer an increased duplex stability analogous to that found in DNA-RNA hybrid structures.

186

Organophosphorus Chemistry OH

OH

O=P-SPh I

SPh

HO OH

O X 0

The kinetics of the chemical hydrolysis of the two diastereomers of the phosphorothioate analogues of uridine-2’-3’-cyclic monophosphate (85) have been determined by HPLC.46 The results have direct relevance in the study of RNA cleaving enzymes and ribozymes. In alkali, both diastereomers are hydrolysed to the corresponding 2’- and 3‘-UMPS only slightly slower than is cUMP hydrolysed to 2’- and 3’-UMP, i.e. the ‘thio effect’ is small. Under neutral and acidic conditions, loss of the uracil base and desulfurisation, respectively, become important. Related to this study is the finding that 2’,3’-cyclic nucleotide 3’phosphodiesterase cleaves only the Sp diastereomer of the phosphorothioate analogues of cUMPS and CAMPSand is thus opposite to the substrate specificity of RNase T1 and R N ~ s ~ The A . ~two ~ sets of enzymes could therefore be complementary in the determination of the configuration of nucleoside 2’,3’cyclic phosphorothioates resulting from hydrolysis reactions of unknown stereochemical course. The phosphorofluoridate of cyclicAMP (86) has been prepared from the Smethylphosphorothioate precursor (87) upon reaction with silver fluoride in a mixture of pyridine and a~etonitrile.~~ The reaction is not stereospecific and gives rise to both Rp and Sp product from stereochemicallypure (89, presumably due to epimerization at phosphorus mediated by pyridine. In contrast to its 2’-deoxy

5: Nucleotides and Nucleic Acids

HoY 0,

x‘

187 0

SMe

o ,

P,

’Y

(85) X = 0; Y

OH

OH

= S:Rp

x = s; Y = 0:sp

derivative, cyclicAMP-F (86) is rapidly converted to 2’,3’-cyclic phosphate which is suggested to occur via initial 5’-C-0-P cleavage by water and anchimeric assistance of the 2’-hydroxyl group. A series of 1-phosphonoalkylidene and 1-phosphonoarylidene nucleoside derivatives (88) and (89) have been obtained via a redox reaction of chlorodiethylphosphite with the corresponding nucleoside or tho ester^.^^ Yields are between 50 and 98% and in the case of (89) 2D ROESY NMR revealed the 8-ex0 derivative to be the major product.

(88) R = H, Me or Ph R’ = H or MeCH2

(89) R1 = P(O)(OEt)2; ex0 R = P(0)(OEt)2; endo

A mild method for detritylation of nucleosides and nucleotides using ceric ammonium nitrate gave an excellent yield of the corresponding acid sensitive phosphoramidite of compound (90).50 A number of dinucleoside phosphate surrogates have been published. The lactone (91), which was obtained via a Wittig reaction on the corresponding 3‘-keto nucleoside, gave good yields of the amide-linked dimer (92) upon reaction with a 5‘-aminonucleoside in the presence of 2-hydro~ypyridine.~’The 3’-thioformacetal-linkeddimers (93) were obtained in yields between 55 and 91% upon reaction of a nucleoside 3’-thiol with the diphenylphosphinate (94) in the presence of DBU.52 The related 5’-thioformacetal-linked dimers (95) were prepared by reaction of a nucleoside 5’-thiol following activation of nucleoside donors (96) using sulfuryl chloride.53The procedure requires in situ trapping of liberated methanesulfenyl chloride with cyclohexene and is applicable to dimers of (95) containing both pyrimidines and purines. A crystal structure of the dimethylene sulfone-linked ribonucleotide (97)has been published.” A mini-duplex containing two sets of Watson-Crick base pairs was observed which displayed many similar characteristics to that of a normal duplex containing RNA such as C3’-endo sugar pucker and anti conformation of the bases.

188

OrganophosphorusChemistry HO

Hov8 Y

O

H

HN

0

(91) B = A o r U

HO OH

DmtoY DmtoY ph2p-o-oY 0 II

O l

0 S)

B

OR (94)

HO

SY

OTWms

I

dR

(93) B = T, AbZ,Gibor 5MeG

Dmtov 0

MeSd

OH

3

Nucleoside Polyphosphates

The adenosine diphosphate derivative (98), a recently discovered metabolite produced during tRNA splicing, has been synthesised by reaction of (99) with (100) in the presence of silver acetate.” Its spectroscopic properties are also reported. The triphosphate (101) has been synthesised by reaction of the free nucleoside with phosphoryl chloride, followed by pyrophosphate. It was found to be an

5: Nucleotides and Nucleic Acids

189

excellent substrate for Taq p ~ l y m e r a s eand , ~ ~its ambivalent base pairing properties have been exploited in a PCR-based random mutagenesis procedure when used in combination with the known mutagenic analogue 8-0x0-dGTP. HO

-O O - rHO ! OH (98)

(99)

?U"

-0

NH

S~P-BU"

f:

-0-P-0-P-0-P-0 O II I

I

OHO OH

::

?lo

&--P

(100)

The triphosphate (102) has been prepared from the CDI-mediated condensation between pyrophosphate and corresponding nucleoside 5'-monophosphate and has been designed for the photoaffinity labelling of HIV-reverse transcript a ~ e . ~The ' analogue is relatively stable but upon irradiation at 365 nm a highly reactive carbene moiety is generated. The triphosphate N-2-(p-n-octylphenyl)-2'-deoxyguanosinehas been synthesised by reaction of the nucleoside 5'-monophosphate with tetrabutylammonium pyrophosphate in HMPA.58The compound displays selective inhibition of DNA polymerase a, compared to 6 and E, but is less selective than the known inhibitor NZ(n-buty1)dGTP. The boron containing triphosphate derivatives (103) and (104) have been synthesised and incorporated into DNA using modified T7 DNA p o l y m ~ r a s e . ~ ~ The polymerase specifically accepts the analogue (104) with the Rp configuration to give DNA containing Sp boranophosphate linkages (105). The Rp analogue of (104) corresponds to the Sp a-thiotriphosphate analogue and the substrate specificity of the DNA polymerase is therefore the same for both triphosphates The structure, thermal stability and reactivity to phosphodiesterases of the novel DNA are also discussed.

190

Organophosphorw Chemistry

NC-BH2 1

II

-0-

r I

,03

(105)

-

The 5’-methylenephosphonatederivative of ATP (106) has been prepared by condensation of the corresponding phosphonate with pyrophosphate using CDI. The analogue was found to be a substrate for T3 RNA polymerase. The novel bis(methy1ene)AZT diphosphate (107) and triphosphate (108) have been synthesised in 14% and 22%yield respectively by condensation of methylene pyrophosphate with AZT in the presence of DCC or via nucleophilic displacement on 5’-O-tosylAZT with bis methylene triphosphate.60 The analogue (108) has a thousand-fold lower affinity for HIV reverse transcriptase than the parent compound which is attributed to the different bond angles and pK, values of the analogue.

f : : :

-O-P-O-P-O-P-CH~ 1 I I

0-

0-

(1 06)

0-

qA HO OH

-O-![CH*-i]:pT I

0

(107) R = 1 (108) /I= 2

N3

A number of lipophilic, triphosphate mimics (109) have been synthesised by reaction of thymidine with the respective derivative (110) followed by deprotection.61 Modelling of the compounds and their inhibitory activity against DNA polymerase ct and HIV reverse transcriptase is discussed. The diphosphate and triphosphate of nicotinamide have been prepared and their substrate properties for a number of polymerase enzymes investigated.62 The diphosphate is a good substrate for polynucleotide phosphorylase from M. luteus.

5: Nucleotides and Nucleic Acids

191 0

(109)

HO R = Me,

0, c

4

Oligo- and Poly-nucleotides

4.1 DNA Synthesis. - The small scale synthesis of oligodeoxyribonucleotidesin quantities required for biochemical and structural studies is now routine. Some improvements or alternatives to the chemistry currently in use have, however, been reported. Bhongle and Tang have suggested the use of diisopropylcarbodiimide in the presence of hydroxybenzotriazole as the condensing agent for the attachment of succinate esters of protected nucleosides to alkylamino-derivatised controlled pore glass.63 Diisopropylcarbodimide has the advantage that its side product, diisopropylurea, is soluble in organic solvents. Two alternative reagents have been suggested for the chemical 5'-phosphorylation of oligonucleotides. 2-Cyanoethyl 3-(4,4'-dimethoxytrityloxy)-2,2-di(ethoxycarbony1)propyl-1-N,N-diisopropyl phosphoramidite can be used in the last round of DNA synthesis.@The dimethoxytrityl group can be removed with acid during synthesis to allow an assessment of the coupling efficiency of the reagent. Following standard ammonia deprotection a 5'-phosphorylated oligonucleotide is produced. Alternatively the dimethoxytrityl group can be left intact and the other protecting groups removed with ammonia. The hydrophobic dimethoxytrityl group can then be used as an HPLC handle to purify the resultant oligomer which can then be liberated by treatment with acid followed by a short aqueous ammonia exposure. An alternative strategy to allow easy purification of phosphorylated oligonucleotides involves the use of 2-n-decylthioethyl protecting group.6s Again the lipophilic protecting group allows purification and can be removed after oxidation of the sulfide to a sulfoxide, followed by fbelimination in aqueous base. 2-Cyanoethoxy-(N,N-diisopropylamino)-3-N-triazolylphosphine (111) has been suggested as an alternative phosphitylating reagent for the preparation of monomers for DNA synthesis.66 Compound (111) is synthesised from the chlorophosphite, chloro(2-cyanoethoxy)-N,N-diisopropylphosphine,and 3-nitro1,2,4-triazole in the presence of triethylamine. Agrawal and co-workers have described nucleoside oxazaphospholidines (112) as alternative synthons for DNA ~ynthesis.~'The reagents are synthesised from the conventionally protected

192

Organophosphorus Chemistry

Dmto

CI-P?] N I

Me

(114) X - S o r O

nucleosides by reaction with 2-chloro-3-methyl-l,3,2-oxazaphospholidine (113). When used in DNA synthesis the phosphotriester (114) is produced which is acetylated due to the capping step. The removal of the phosphate protecting group is achieved along with removal of the other protecting groups by treatment with concentrated aqueous ammonia at 55 "Cfor 10 hours. The new phosphitylating reagent has the advantage that the starting materials are cheaper than those for the conventional 2-cyanoethyl protection. The hexafluoro-2-butyl group has been proposed as an alternative to the cyanoethyl masking function commonly used in phosphoramidite chemistry.68Diisopropylamino and diethylamino (115a and b) reagents were evaluated. The required chlorophosphite was easy to prepare and could be purified by distillation at ambient pressure.

Dm"vp Dmto-Pp (115a)

(1 15b)

Dowex@ resin (H+form) has been suggested as an improved method of detritylation of synthetic oligon~cleotides.~~ The dimethoxytrityl cation remains bound to the Dowex, avoiding, the need for removal of the alcohol from solutions of the oligonucleotide. A universal ally1 linker for the synthesis of oligonucleotides, 9-0-(4,4'dimethoxytrity1)-10-undecenoic (116), has been described. Ally1 cleavage occurs under conditions that are orthogonal to the conventional protecting groups in DNA synthesis thus allowing post-synthetic manipulations to be carried out on the solid support.70 A novel thymidine silyl linked support, (117), has also been

5: Nucleotides and Nucleic A c i h

193

described.71The oligonucleotide can be liberated very quickly with tetrabutylammonium fluoride. Oligonucleotide synthesis has been conducted on supports consisting of a thin layer of polystyrene grafted onto PTFE.72Reagents for a 5’3’4rected DNA synthesis have been reported.73

0

I

0

o h K , - @ H

A rapid one-pot method has been described for the attachment of the 3 ’ 4 succinyl derivatised nucleosides to LCAA-CPG. The method involves reacting triphenylphosphine with 2,2’-dithiobis(5-nitropyridine) to generate (118) which reacts with the succinylated nucleoside to give the activated acid (119). Coupling of (119) to LCAA-CPG is rapid and gives the usual loading yields expected. NPent-4-enoyl nucleosides have been utilised in an H-phosphonate mediated oligonucleotide assembly.74The protecting group is introduced to the exocyclic amino function of the nucleosides by treatment with pent-4-enoic anhydride under transient protection conditions. Unmasking of the amino groups can be performed simultaneously with oxidation by exposure to iodine in a 2% pyridine water or pyridine methanol solution or by exposure to aqueous ammonia at room temperature for 1-2 hours if phosphorothioate oligonucleotides have been synthesised. Oligonucleotides containing methyl phosphotriester and methyl phosphonate linkages have been prepared using this masking group ~ t r a t e g y . ~ ’ . ~ ~

194

Organophosphorus Chemistry

Some attention has been devoted to the use of photolabile protecting groups in A particular DNA synthesis and a comparative study has been carried problem is associated with the use of benzoyl protecting groups which react under the photolysis conditions. The solid support (120) has been demonstrated to produce yields of oligonucleotides which when compared to hydrolytic cleavage vary between 67% and 82%.78

Dmto-P

A method for preparing random point deletions in oligonucleotides has been de~cribed.’~ Depending on the desired level of mutations, various concentrations of dichloroacetic acid replaces the conventional trichloroacetic acid and capping is omitted from the synthesis cycle. The enzymatic synthesis of DNA has been described using a circular DNA template.**Multiple copies of the template are produced without the requirement for the heating and cooling cycles associated with PCR. The concatermeric products can be cleaved with enzymes to yield shorter multiple copies of oligonucleotides. An automated multiplex DNA synthesiser has been developed which can simultaneously and rapidly synthesise up to 96 different oligonucleotides. A strategy has been designed to minimize the number of dimers required for the synthesis of trimer phosphoramidite building blocks encoding all 20 amino acids.82 This requires a set of 7 different dimer blocks which can be used to synthesise all required antisense sequences. A set of 4 trimer phosphoramidites (121) has been prepared and their application to the synthesis of mutants of thymidylate synthase has been demonstrated.

5: Nucleotides and Nucleic Acidr

195

4.2 RNA Synthesis. - Methods for the synthesis of RNA are now routine but less efficient than DNA synthesis. The most popular phosphoramidite reagents employ acyl protecting groups for the exocyclic amino functions of the nucleosides, dimethoxytrityl for the 5’-hydroxyl function and 2’-0-tertbutyldimethylsilyl (Tbdms) for the 2’-hydroxyl function. Usman and co-workers have studied the coupling efficiency of the monomers and deprotection of the resultant oligorib~nucleotides.~~ The use of 5-ethylthio-1H-tetrazole was found to be more efficient than the conventional tetrazole coupling catalyst. Reduced deprotection times were achieved by the use of methylamine for removal of base protecting groups and triethylamine trishydrofluoride in N-methylpyrolidinone for the removal of the silyl protection. Purification of the resultant oligoribonucleotideswas achieved by anion exchange chromatography. A comparative evaluation of methylamine, methylamindammonium hydroxide and ammonium hydroxiddethanol for the deprotection of oligonucleotides has also been ~ n d e r t a k e nIn . ~order ~ to avoid the possible transamination of cytosine when benzoyl protection is employed for the amino group an acetyl protected monomer was used instead. Methylamine or methylamine/ammonium hydroxide mixtures were found to liberate the oligoribonucleotide at room temperature in 90 minutes and improve the yield of the desired product. The synthesis of oligoribonucleotides using formamidine based protection for A or G and isobutyryl for C has been reported.85The amine protecting groups were removed by exposure to aqueous ammonidethanol (3:l) for 3-5 hours at 55 “C. The 2’-O-silyl groups were removed by tetrabutylammonium fluoride in THF or neat triethylamine trishydrofluoride. For purification of the resultant oligomer by reversed phase techniques, the 5’-dimethoxytrityl protecting group could be left on when the former desilylating reagent was used and then removed after purification without causing phosphate migration. Anderson and coworkers have recommended anion exchange for the large scale purification of RNA.~~ The use of a high-loaded polystyrene (HLP) support has been described for the large scale synthesis of RNA.87 Biologically active ribozyme sequences were synthesised on a 200 pmol scale using this support in conjunction with 2’-0-tertbutyldimethylsilylmonomers and 5-ethylthio-1H-tetrazole as the activating agent. An alternative protecting reagent to the commonly used silyl group has been reported.88The fluoride labile p-nitrobenzyloxymethyl may also be used to mask the 2’-hydroxyl function in RNA synthesis. Kool and co-workers have reported the rolling circle synthesis of RNA using circular oligonucleotidesas the template for RNA synthesis.89 The Synthesis of Modified Oligodeoxynucleotidesand Modiiied Oligoribonucleotides 4.3.I Oligonucleotides Containing ModifiedPhosphodiester Linkages. - Interest in the area of oligonucleotides containing modified phosphodiester backbones continues as the search for analogues with enhanced stability to nucleases is important in the potential use of oligonucleotides as chemotherapeutics.The area of antisense oligonucleotideshas been reviewed this ~ e a r . ~ . ~ ~ 4.3

196

Organophosphorus Chemistry

R

0

1

X=SorSe R = H or Me

DmtoY ""0 or

0

'P-O%CN /

RO

Oligonucleotides containing phosphorothioate internucleoside linkages (122) have been of interest for several years now. Full details describing the stereospecific synthesis of phosphorothioates using the oxathiaphospholane monomers (123) has now been publishedg2and the mechanism of the reaction in~estigated.~~ The oxidative sulfurisation of phosphite triesters to give the corresponding phosphorothioate triesters is known to be stereospecific. An approach to obtain pure phosphite triester diastereomers has been described in which chirally pure monomers (124) are coupled to the 5'-hydroxyl of the second nucleosidic component in the presence of base.% The use of a large excess of components (124) allows the formation of the corresponding triester with stereoselectivities greater than 80%. Two new classes of sulfurisation reagents have been suggested which can replace the oxidising solution commonly used in DNA assembly via the phosphoramidite approach. A number of disulfides of arylsulfonic acids, bis (p-toluenesulfonyl)disulfide, bis(p-chlorobenzenesulfonyl)disulfide, bis(benzenesulfonyl)disulfide, and bis(p-methoxybenzenesulfony1)disulfide (125a-d), have been investigated for their ability to convert internucleoside cyanoethyl phosphites to a phosphorothioate triester. All the reagents are successful in this conversion but the derivatives ( 1 s ) and (125d) are preferred due to their solubility in acetonitrile affording ready a ~ t o m a t i o n 1,2,4-Dithiazolidine-3,5.~~ dione (126) and 3-ethoxy-l,2,4-dithiazoline-5-one (127) have also been found to be effective sulfurising agents for use in the synthesis of oligonucleotides containing phosphorothioate linkages by phosphite triester chemistry.% Improve-

5: Nucleotides and Nucleic Acidr

197

ments in the yields of phosphorothioate containing oligonucleotides have been achieved by the use of triethylsilane in the presence of dichloroacetic acid in dichloromethane as a dimethoxytrityl cation sca~enger.~’ Electrospray ionisation mass spectrometry has proved useful to indentify the N-1 impurity in oligodeoxynucleotides containing phosphorothioate internucleoside linkages.98

Advances in the synthesis of DNA containing phosphorodithioate (128) internucleoside linkages have also been achieved. Synthesis of the phosphorodithioate DNA was achieved using the appropriately protected deoxynucleoside 3’-phosphorothioamidites, (129), which were prepared from a protected deoxynucleoside, tris(pyrro1idino)phosphine and ethanedithiol monobenzoate in a one flask reaction.99 The synthesis of phosphorodithoate DNA has been also been investigated using dithiaphospholane based reagents (130).loo The dithiaphospholane undergoes a ring opening condensation with the 5’-hydroxyl group of support bound nucleosides or nucleotides in the presence of DBU. The approach requires the use of a DBU stable sarcosine support linker and N-methylpyrrolidin-2-ylidenylprotecting of the exocyclic amino functions of the nucleobases. Phosphorodithioates have also been synthesised using the thiophosphotriesters (131a) and (131b) which are readily prepared from the corresponding dichloro compound.lol The dithiophosphorylating reagents have been used in a solid supported synthesis of a nonamer of deoxythymidine phosphorodithioate.

0 ‘

198

Organophosphorus Chemistry

DmtoYp

S

(131)

a; R = 1-hydroxybenzotriazolylb; R = 6-nitro-1-hydroxybenzotriatolyl-

Kuimelis and McLaughlin have prepared an oligonucleotide containing an internucleoside 5'-phosphorothiolate RNA linkage (132).lo2-lo5 Although embedded within an oligoribonucleotide, a deoxynucleotide synthon, (133), was prepared by displacement of the 5'-tosyl derivative of 2'-deoxyadenosine with triphenylmethylmercaptanin the presence of sodium hydride. The enzymatic and non-enzymatic cleavage properties of the oligoribonucleotide were studied.

O,

OH

Methylphosphonate internucleoside linkages (134) have also received considerable attention over the past few years. An alternative synthesis of methylphosphonate containing oligonucleotides has been developed by Stec and coworkers.lo2 5'-0-dimethoxytrityl-(N-protected) nucleoside 3'-@(methanephosphonofluoridates) (135), can be prepared from 5'-0-dimethoxytrityl-(Nprotected) nucleoside 3'-O-(Se-methylmethanephosphonoselenoates) and react with the, 5'-hydroxyl groups of nucleosides in the presence of DBU. The phosphoramidite (136) has been described in the synthesis of oligonucleotides containing tritium labelled methylphosphonate linkages for biodistribution and biostability studies.lo6 Oligonucleotides containing several (cyanomethy1)phosphonate linkages (137) have been synthesisedlo7using the 3'-phosphoramidite of the corresponding dinucleotide. Duplexes containing the modified linkages of the Rp configuration displayed a slightly lower stability than those containing normal phosphodiester linkages.

5: Nucleotides and Nucleic A c i h

199

‘OY DmtoYp O\ 40 P

Me/

(134)

‘F

(135)

DmtoYp N-Pent-4-enoyl protected n~cleosides’~(see section of DNA synthesis) have been utilised in an H-phosphonate-mediated assembly of oligomers containing methyl phosphotriester (138) and phosphoramidite (139) linkage^.^^^*^* The stereospecific conversion of H-phosphonates into phosphoramidites upon treatment with butylamine in carbon tetrachloride has been monitored by NMR and found to proceed with inversion of stereochemistry at phosphorus.10g

O\ / o P’

H2Nfl

‘OY 0

b

200

Organophosphom Chemistry

The synthesis of oligodeoxynucleotideswith N3’-P5’ phosphoramidite linkages (140) has been accomplished using 5’-O-dimethoxytrityl-N-acyl-3‘-amino-2‘,3‘-

’

dideoxynucleosides. lo The amino nucleosides were utilised in chain elongation in a carbon tetrachloride driven oxidative coupling with a 5’-H-phosphonate diester group. The structure of oligodeoxynucleotide duplexes with N3’-P5’ phosphoramidite linkages (140) has been studied by NMR.”’

“Y B = T or Acbz

Peptide nucleic acids (PNA) continue to receive a lot of attention. The synthesis of PNA-DNA hybrids has been reported. l2 The base pairing properties of alanyl peptide nucleic acids containing an amino-acid backbone with altering configuration has been ~ t u d i e d . ” ~ *The ” ~ synthesis of ‘retro-inverso PNA’ has been described by Nielsen and co-workers using the monomer reagent (141).115*116 An alternative synthetic strategy for the assembly of PNA has been developed using a monomethoxytrityl protecting group.’” A new DNA analogue based on 0

T

CXo I

H-BW N (143)

R1 = H or Me R2 = H or &CH20H or a-CH20H R3 = Et or Me R4 = OMe or H X = CH2 or 0

5: Nucleotides and Nucleic AcidF

201

ornithine has been assembled using the synthon (142).11* The reagent (143) has been used for the preparation of PNAs containing a dipepeptide as the repeating monomer unit. l 9 The resulting polymers display an improved water solubility but do not appear to hybridize to the complementary DNA sequence. The synthesis of methylene(methy1amino) linked oligonucleotides (144) has been automated and performed on solid phase. 120 Oligonucleotides having hydroxymethylphosphonate internucleotide linkages (145) have been synthesised from the corresponding H-phosphonate via a trimethylphosphite intermediate (146).121 0 '

*' iN-Me

I 0

(145)

(144)

OTms

r-

ob Y = OH, X = H, B = T Y = OMe, X = H, B - T Y =H, X - H , 6 - U Y = OMe, X = OMe, B = U

o $

x

(147)

Oligonucleotides containing the sulfide linked dinucleoside units (147a-d)have been prepared122and their preference for binding to RNA has been explored. A series of modified oligonucleotides containing the internucleotide linkages

202

Organophosphorus Chemistry

(148a-f) with four or five atom spacers have been prepared.123Oligonucleotides containing the four atom spacer displayed higher melting temperatures when hybridised with complementary sequences. However the five atom secondary amine was less favourable than the four. r

T

(148) a; X = CH2CH2NHb; X = CH2CH2CH2NHC; X = CH~CH~NACd; X = C H ~ C H ~ C H ~ N A C e; X = -CH2CONHf; X = CH2CH2CONH-

Using a dimer block assembly strategy a series of oligonucleotideswith amide linkages were prepared using the phosphoramidite reagents (149a-d). 124 When hybridised to a complementary oligonucleotide the acyclic linkages were found to offer better duplex stabilisation. A dimer block strategy has also been used to synthesise DNA containing an acyclic nucleoside and a carbamate linkage using the synthons (150a) and (150b).1259126 The phosphoramidite (151) has been used to synthesise oligonucleotides containing a novel carboxamide linkage and an 'acyclic' nucleoside analogue. 27 Duplexes containing the modified linkages possessed greatly decreased melting temperatures.

Dm"-P

ov x

b;X=

Y-

n

-NvNMe Me

203

5: Nucleotides and Nucleic Acids

DmtoTodT Dmto-P 0 I

NH

(150a)

(1 50b)

1

\

0

Oligoribonucleotides with non-ionic dimethylene sulfone bridges (152) have been prepared by Benner and co-workers.128The properties of these modified RNA molecules have been investigated. The synthesis of the novel nucleoside dimer analogues (153a-c) which contain an acyclic nucleoside and a carbamate linkage has been accomplished and their properties have been investigated.125~126A trinucleotide containing 2',5'-formacetal linkages and a conformationally restricted ribose was synthesised and then attached to controlled pore glass (154) to achieve ultimate incorporation to the 3'-end of an olig~nucleotide.'~~ Oligonucleotides containing three phosphorothioate linkages and a methyl phosphonate flank could be alkylated with pivaloylmethyl iodide, S-acetylthiomethyl iodide and methylacylthioethyl iodide to yield neutral oligonucleotides

204

Organophosphorus Chemistry

0

I

OH (1 53a)

Dmto-r

0

NH

OH HO (153b)

(153c)

with enhanced cellular permeability.130J31All the alkyl groups could be removed by carboxyesterases present in cell extracts. The synthesis of a range of thiono triester modified oligonucleotides has been reported using reagents (155ae).I3*The syntheses employed very base labile tertbutylphenoxyacetyl protecting groups for the exocyclic amino functions of the nucleobases which requires only a two hour treatment with ammonia at room temperature for deprotection. DNA containing 3'-3'-phosphodiester and 5'-5'-phosphodiester linkages has been described by Beaucage and co-workers and Agrawal and c o - w ~ r k e r s . l ~ ~ - ~ ~ ~ The resultant modified DNA has higher affinity for complementary single stranded DNA than RNA. The triphosphates of 2'-5'-oligoadenylate trimers are implicated in at least one of the mechanisms of the antiviral action of interferon and bind to and activate a RNaseL resulting in the cleavage of viral mRNA and the inhibition of viral replication. In order to study the cellular function of oligoadenylate, the'25 I-labelled conjugate (156) has been synthesised. Specific antibody recognition of

5: Nucleotides and Nucleic Acids

205 a; R =

DmtoYp b; R =

A

/O\

N

RO

b

c;R=

d; R = Prl

(155)

e;

= -(CH2)15Me

(156) was comparable to that of the unlabelled oligoadenylate. The cholesterol conjugates of 3’-deoxyadenosine-~ontaining trimers (157)136have been synthesised using phosphite triester chemistry. The coupling of the 5’-phosphoramidite (158) with the 2’-hydroxyl of a suitably protected cordycepin 2’-5’ phosphotriester, or conversely the coupling of the corresponding 3’-phosphoramidite dimer with (159) were investigated, of which the latter was more efficient. Removal of the terminal acetyl group, coupling with cholesteryl chloroformate, followed by deprotection afforded the desired trimer conjugate. In addition, several palmitoyl labelled oligoadenylates (160) have been synthesised using phosphite triester chemistry and the phosphoramidite monomer (161).

HO

0,

-0’

9

p:oM HO

0,

OH

-0’

H .N

Organophosphorus Chemistry

206

(157) R = -CH2CHpC+cholesteryl

npe = 2-(4-nitrophenyl)ethyl npes = 2-(-nitrophenyl)ethoxysulfonyl

U

5: Nucleotides and Nucleic Acidr

207

4.3.2 Oligonucleotides Containing Modified Sugars. - Usman and co-workers have synthesised a number of 2’-modified nucleoside phosphoramidites (162a-d) and incorporated them into oligoribonu~leotides~~~ with the aim of producing nuclease resistant ribozymes. The synthesis of oligonucleotides bearing 2’-amino and 2’-azido functions has been achieved using phosphotriesterchemistry. 38

’“OR I

P (1 62b)

Dmto o

x

X = CH2 or CF2

(1 62c)

(1 62d)

5’-C-Branched thymidines bearing 5’-(S)-C-aminomethyl, Y-(S)-C-azidomethyl, and 5‘-(S)-cyanomethylhave been prepared from the key intermediate 5’(S)-epoxy derivative. 5‘-C-Nitromethylthymidineand 5’-C-ally1 thymidine derivatives were also prepared from the 5‘-aldehyde derivative. The phosphoramidite reagents (163a-c) were prepared and utilised to synthesise oligonucleotides. Substitution of thymidines close to the 3’-termini of oligonucleotides gave comparable melting temperatures to unmodified oligonucleotides in duplexes but significantly enhanced nuclease resistance. 39 4‘-C-hydroxymethyl(thymidine)has been incorporated into oligonucleotides and also used to synthesise branched oligonucleotides.lrnThe resultant oligonucleotides possessed enhanced resistance to nucleases and were found to bind well to RNA but duplexes with DNA were de~tabi1ised.I~~ 3’-C-hydroxymethyl-aldopentopyranosylnucleosides have also been incorporated into synthetic DNA. 142 Oligonucleotides containing compressed backbones (164) have been prepared using the sugar modified, phosphoramidite reagent (165).143Oligonucleotide duplexes containing (164) showed greatly decreased stabilities. The oligonucleo-

208

OrganophosphorusChemistry

(163) a; R OMe b; R=NHCOCF3 C; R = C H Y C H 2 I

tides with restricted conformational flexibility have been prepared using the synthon (166). la An oligonucleotide constructed entirely of the modified sugars displayed no affinity for D N A or RNA. Beaucage and co-workers have prepared thymidine derivatives which contain an ethyl linkage inserted into the glycosidic bond and these have been transformed into reagents suitable for D N A synthesis (167ad).133 DmtO

H

TMmsDmtO o%T

+ epimer (167a and b)

+ epimer

(167c and d)

Oligonucleotides bearing a 2'-anthracene unit have been prepared using the phosphoramidite reagent (168).145*146 The modified nucleic acid binds to both DNA and RNA but an induced change in CD due to the anthracene chromophore was only observed in the case of DNA and not RNA.

5: Nucleotides and Nucleic Acids

209

A trimer oligoribonucleotide bearing a 5’-amino function, 2’-5’-phosphodiester linkages and an acyclic sugar moiety at the 3’-nucleosideposition (169) has been prepared and characterised by Pfleiderer and co-worker~.’~’

HO

O,p.’p

-0’ ‘07

The phosphoramidite monomer (170) has been used for the solid phase synthesis of 2’-phosphorylated uridylic acids.14* These 2’-phosphomonoester, 3’5’-phosphodiester linkages have been recently found in a number of spliced pretRNA molecules. Following synthesis, the bis(2-cyano-l ,1-dimethylethoxy) protected groups are removed with DBU and the phosphorothioate oxidised to the corresponding phosphate using iodine. Addition of N,O-bis-(trimethylsily1)acetamide to the support bound polymer prior to deprotection with DBU prevents premature cleavage of the polymer form the support. Labelling of the polymer via its 2’-phosphate group as a biotin conjugate or reaction of its Z-thiophosphoryl precursor with monobromobimaneare also described. 4.3.3 Oligonucleotides Containing Modijied Bases. - A site specific ’% label I-was introduced to the 6-amino group of adenine using a 6-methylpurine nucleotide synthon. 149 Subsequent treatment of the oligonucleotide with ”N- ammonia displaced the oxidised methylthio group on the purine yielding the desired modification.

210

Organophosphorus Chemistry

Dmto-P;bz

2’Deoxyformycin has been synthesised from the ribose analogue by a deoxygenation procedure and then converted into a suitable reagent for oligodeoxynucleotide synthesis (171).150 Formamidine protection of the exocyclic amino group was employed. A phosphoramidite derivative of 8-methoxy-2’deoxyadenosine has been prepared and used to synthesise oligonucleotides containing this modified nucleoside. N=CH(NMe2)

I

d, /A /

o\ NC-o/p-N

.k

Oligonucleotides containing 2-aza-2’-deoxyinosine have been prepared using the phosphoramidite derivative (172) which has a photolabile 2-nitrobenzyl protecting The ability of 2-aza-2-deoxyinosine to act as a universal base was studied and it was found that similar destabilisation of the duplex resulted when the analogue was placed against any of the four natural nucleobases. A similar result was also obtained when 2’-deoxyisoinosine was incorporated into oligonucleotides.Seela and Chen have developed the H-phosphonate or phosphoramidite monomers (173a)and (173b) for the incorporation of this modified nucleoside into DNA. 153 Oligonucleotides and their methylphosphonate containing derivatives containing 2’-0-methylisocytidine have been synthesised using the phosphoramidite (I 74a) or the methylphosphonamidite (174b).ls4 In each case increased coupling times were required during oligonucleotide synthesis and in the latter case

5: Nucleotides and Nucleic A c i d

211

Y (173) a ; X = -P'

DmtoY 0 I X

I 0-

conditions for deprotection compatible with the methylphosphonate linkage were investigated. The stability of a series of oligonucleotide duplexes containing 7-deaza-7substituted 2'-deoxyguanosines has been described.155 The H-phosphonate and phosphoramidite synthons (175a) and (175b) were utilised in synthesis and the 7-iodo substituted oligonucleotide duplexes were found to have enhanced melting temperatures. 0

R-O

h/\

bMe

"""Y 0

I

X (174) a; R = Me

b; R = \o-CN

(175) a; R = I b; R = M e

Oligonucleotide duplexes containing the modified base 5-methylcytosinedisplay increased thermal stabilities compared to the unmodified duplexes. A number of alternative protecting groups have been investigated for the synthesis of oligonucleotides containing 5-methylcytosine, of which the Fmoc group could be removed under mild conditions.156 This allowed the synthesis of oligonucleotides containing 5-methylcytosineand the ammonia-sensitivebase, 5-bromouracil. 5-Nitroindole and 3-nitropyrrole have been assessed as universal bases in primers for dideoxy sequencing. The 5-nitroindole nucleoside was found to be superior.157The melting temperatures of oligonucleotides containing acyclic universal base derivatives (176a) and (176b) was found to exceed those of the 3-nitropyrroleana10gue.l~~

212

Organophosphorus Chemistry

O r n t O V

HO

I

b;

GNO*

B = N.

N

I

(177)

Several modified nucleosides have been incorporated into oligonucleotides in an attempt to stabilise triple helices. Oligonucleotidescontaining 2,dquinazolinedione as a substitute for thymine have been synthesised using the phosphoramidite reagent (177).lS9The introduction of the one or more modifications slightly destabilised the resultant triplexes. A 2'-deoxycytidine analogue N4-(6-amino2-pyridiny1)deoxycytidine was prepared from a suitably protected 4-triazole derivative of deoxyuridine and suitable derivatised for DNA synthesis as (178).160 The analogue was found to interact with a CG base pair in the third strand of a triplex at pH 7. A pyrimidine nucleoside that functions as a bidentate hydrogen bond donor has also been synthesised and converted to its phosphoramidite reagent (179). Phosphoramidite derivatives of 2'-O-methyl-6-oxocytidine and its 5-methyl derivative have been used to synthesise oligonucleotides capable of pH independent triple helix formation.lci2 Synthesis of oligonucleotides containing 06-modified deoxyguanosines bearing a C6-psoralen or C6-acridine has been accomplished.163

NH

1

0

Dmto-P ,'-' O\

NC-

0

5: Nucleotides and Nucleic Acidr

213

Baillet and Behr have incorporated P-deoxyribosylformamideinto oligonucleotides using the phosphoramidite reagent (180). Deoxyribosylurea and deoxyribosylformamide were obtained by oxidative degradation of thymine. The urea derivative exhibited exchange of the anomers but it proved possible to obtain pure samples of the fbdeoxyribosylformamide.

Dmto$cI 0

MmtoYHcHo /c

NC-dp-NT

NC-dp-NY

A

A fluorescent guanosine analogue has been synthesised and incorporated into oligonucleotides using the synthon (181). 165 The fluorophore within DNA has been used to develop a continuous fluorescence assay for the HIV-1 integrase 3’-processing reaction. The automated synthesis of platinated oligonucleotides has been achieved using H-phosphonate oligonucleotide assembly. The platinated thymidine derivative (182) was synthesised from the corresponding H-phosphonate derivative of thymidine by deprotonation with potassium hydroxide and then reaction with trans-[(NH&PtCl,]. Stockley and co-workers have described the synthesis and incorporation into oligonucleotides of 6-thioguanosine using the phosphoramidite reagent (183). 167 The nucleoside was utilised to study structure-function relationships of catalytic RNAs.

Dmto-P ?

H-P=O I

0-

Organophosphorus Chemistry

214

The phosphoramidite (184) has been used for the synthesis of 5-fluorocytidine containing oligoribonucleotides.168 N-Acyl-protected 5-fluorocytidines are very labile during oligonucleotide synthesis and (184) is converted to the desired 5-fluorocytidineduring deprotection.

Hypermethylated guanosine-capped mRNA molecules are important in cellular transport and RNA splicing. The chemical synthesis of a 5’-terminal 2,2,7trimethylguanosine-capped tri ribobonucleotide has been described by condensation of (185) with (186) in the presence of CDI in 40% yield.169The synthesis includes a novel three step synthesis of 2N,2N-dimethylguanosine from guanosine. The product was characterised by proton and phosphorus NMR. 0

5: Nucleotides and Nucleic Acidr

215

The 1-deazaadenine-containingtrimers (187) have been synthesised in order to investigate the role of this ring nitrogen in the biological activity 2’-5’-oligoadenylate trimers. The phosphodiester methodology was used for the synthesis using one of the phosphodiester building blocks (188) and triisopropylbenzene sulfonyl chloride and N-methylimidazole.

HO

(188) icA

5

=

OH

ldeazaadenine

Linkers

Letsinger and co-workers have addressed the chemical ligation of circular oligonucleotides and loop structures.171 Oligonucleotides containing a 3’-0phosphorothioate and a 5‘-0-tosyl group were found to form -OP(O)-(0-)-Slinkages when templated to react to form circular oligonucleotides or loop structures. The 5’-O-tosyl group was introduced using a 5’- 0-tosylthymidine-3’(cyanoethy1)-phosphoramidite reagent.

216

Organophosphorus Chemistry

Alkoxy derivatives of 6-chloro-2-methoxy-9-methylacridine have been attached to oligonucleotides using either phosphoramidite, H-phosphonate or phosphate triester oligonucleotideassembly (189a-c).172

(189a)

NC

Me 0 ~ 0 - ( c H 2 ) " - 0 - t 7 - H II 0CI

H

(189b) n = 6 or 7

-o-!-,h

&0-(cH2)6

CI

\

0I

+'

/

H (189c)

The synthesis of monomannoside (190) and dimannose derivatives anomerically linked to a hydrophobic spacer have been used to synthesise oligonucleotides bearing a sugar moiety.173 AcO

7 OAc

Modified 2'-deoxyuridine derivatives (191a-c) suitable for the introduction of primary amino functions into oligonucleotides have been synthesised from 5(methoxycarbonylmethy1)-2'-deoxyuridine.174

5: Nucleotides and Nucleic Acidr

217 0

NO ' HN%CH2coR

(191) a; R = NH(CH2)2NHCOCF3 b; R = NH(CH2)6NHCOCF3 C; R = NHC~H~N(CPH~NHCOCF&

A 2'-deoxyuridine analogue bearing a pendant adenine moiety has been prepared and suitably protected for oligonucleotide synthesis.17' When incorporated into DNA the resultant oligomer has an identical melting temperature when hybridised with its complement. A photoisomerisable linker, (192), containing an azobenzene unit has been described.la The linker reagent can be used to connect two oligonucleotides and the resultant DNA has an altered UV-visible spectrum after irradiation which can be accounted for by cis-trans isomerisation. An alternative stilbene dicarboxamide linker, (193), has also been reported.176The sensitivity of this unit to light is affected by the nucleotide abutting the linker.*77Incorporation of this reagent into a 22mer oligoribonucleotide possessing the HIV protein rev response 0 DmtO-

N H

b

v

21 8

Organophosphorus Chemistry

element (RRE) was found to be as effective as a UUCG tetra loop and better than a TTTT tetra loop and a triethylene glycol linker at stabilising this structure which was able to bind to Rev as well as a 96mer unmodified RNA structure. The stability of duplexes joined by various linkers has been studied by melting temperature and NMR.178 Of the three linkers studied (194a-c), the greatest enhancement in stability of the duplex was afforded by five or six ethylene glycol units. -[PO2-0-(CH2)3-

012-

PO,-

(194a)

A protected thiopropyne derivative (195) of 2’-deoxyuridine suitable for use in DNA synthesis has been described.179The reagent was synthesised from 5-iodo2’-deoxyuridine via palladium catalysed coupling with hydroxy propyne. Subsequent formation of the mesylate allowed displacement of the hydroxyl function with thiobenzoate. After synthesis and deprotection the modified nucleoside was used to form circular oligonucleotides with disulfide linkages across the centre. The resultant circular DNAs displayed high affinity binding to a single stranded DNA forming a triplex structure. The phosphoramidite (1%) has been synthesised which is also designed to allow the specific disulfide-mediated cross-linking of oligonucleotides.lSo

The synthesis of oligonucleotides containing interstrand cross links to bifunctional pyrroles has been reported. lS1 The modified nucleoside phosphoramidite (197) was incorporated into DNA using very base labile protecting groups for other functions in the molecule. The 6-0-trimethylsilylethyl group is relatively stable when the 2-fluoro group is present, but is labile when the oligonucleotide is exposed to bis-electrophiles and the fluoride is displaced by an amine. The crosslinking of an S-alkyl bromoketone derivative (198) of 4-thi0-2’-deoxyuridine to the N7 of guanine in a complementary oligonucleotide has been demonstrated.’**

5: Nucleotides and Nucleic Acids

219

O*SiMe3

NC-ORP-N

Y

4-

d(TAATACGAC0

O-CACTATA)

The phosphoramidite (199) has been synthesised for incorporating aliphatic amino groups into oligonucleotides for cross linking.183 Following oligonucleotide synthesis and deprotection, a free carboxyl group is generated by reaction of the free amino group with succinic anhydride. Carbonyl diimidazole allows the formation of amide cross-links in up to 16% yield between the free amino residue of one chain and the carboxylic acid moiety on the other chain. A photocleavable biotin linker reagent (200) has been reported.lW The reagent can be used in the last cycle of oligonucleotide assembly to yield biotinylated oligonucleotide which can then be purified on a streptavidin column. Upon irradiation

Me,

.O CH

220

Organophosphorus Chemistry

the linker is cleaved yielding a 5'-phosphorylated oligonucleotide. A photocleavable universal solid support for DNA synthesis that releases 3'-alkylamines has been described.185An alternative reagent, (201), for the synthesis of biotinylated oligonucleotideshas been described. 86 An oligonucleotide bearing a 3'-phosphoryltyrosine residue has been synthesised from the modified tentage1 or controlled pore glass solid support (202).18' The hydroxyl group of tyrosine was protected with a levulinoyl group which could be removed with sodium borohydride. A new solid support, (203), has been prepared for the synthesis of 3'-derivatised oligonucleotides.188 The support bears two orthogonal protecting groups 4-methoxytriphenylmethyland 4-methoxyphenyl for the hydroxyl functions. The latter protecting group can be removed after oligomer assembly with Ce(IV)(NH&NO3)2 and further manipulation can be performed at this position with a variety of oligonucleotidemodifying reagents. 0 0

NHFmoc

H

n

MmIC

Oligodeoxynucleotides containing internal non-nucleotidic linkers (2041s-c) have been tested for their ability to promote cleavage of a complementary RNA strand. 189A new solid phase method for the synthesis of oligonucleotide peptide conjugates has been described.19* The modified solid support (205) possesses masked hydroxyl and amino functions with orthogonal protecting groups that can be removed for either peptide or oligonucleotide synthesis. Thuong and coworkers have prepared an oligonucleotide-peptideconjugate possessing the active site peptide of ribonuclease A and a copper complexing metallopeptide.19' A modified uridine suitable for the post synthetic attachment of various amines has been described.192The modified uridine (206) was utilised in oligonucleotide synthesis and reacted with lithium hydroxide, methanolic ammonia, ethanolamine, ethylenediamine and 6-aminohexanol and 1,12-diaminododecane to yield of variety of modified oligonucleotides.

5: Nucleotides and Nucleic Acids

22 1

a; R =

kNiN4g H

C;

R=

H

H

0

Meunier and co-workers have studied the influence of linker length on the cleavage of DNA by an oligonucleotide tethered to a metall~porphyrin.'~~ A spermine linker was demonstrated to give the highest cleavage efficiencies. Diazapyrene tagged oligonucleotides have been synthesised and utilised to crosslink to a complementary DNA upon irradiation.'% Alkaline induced scission of the photoadduct demonstrated that the cross-links were localised. Bashkin and co-workers have prepared a variety of terpyridine and bipyridine conjugates with nucleosides (207ad) suitable for incorporation into oligon u c l e o t i d e ~ .The ~ ~ ~analogues are designed to deliver metals to the major or minor groove of DNA.

Organophosphorus Chemistry

222 0

0

(207a)

(207b)

(207c)

(207d)

5: Nucleotides and Nucleic Acia3

223

F

Me

F DmtO

6”

Me

Me

DmtO NC

(208a)

(208b)

Kool and co-workers have prepared a set of 2’-deoxynucleoside isosteres designed to be used in place of looped nucleotide bases in hairpins and circular DNA. 196 The phosphoramidite reagents (208a-c) were used in oligomer assembly. An oligonucleotide with a pentanucleotide bridge consisting of (208a)5 was found to be more stable than when the bridge was formed from Ts.l-Deoxy-l-phenylP-D-ribofuranose has been synthesised and incorporated into oligoribonucleotides using the synthon (2W).197 A C-60 linked oligodeoxynucleotide has been demonstrated to facilitate sequence-specific modification of guanosine residues in a complementary oligonucleotide.* 98 The hybridisation of an oligonucleotide conjugated to Horse Radish Peroxidase can be directly measured as an electrical current which results from detection of the peroxide reaction upon hybridisation.199 A reagent to attach an amino bearing trityl group, (210), has been reported. After DNA synthesis the amino function was liberated and acylated with Nhydroxysuccinimidyl p-benzoylbenzoate. The resultant oligonucleotide could

fl

DmtO

9

O-TWms

224

Organophosphorus Chemistry

then be cross-linked to bovine serum albumin and the resultant conjugate was able to hybridise with a complementary oligonucleotide.200 A novel pyrene nucleoside analogue has been synthesised and suitably derivatised for oligonucleotide assembly as (211).201An alternative reagent, (212), has been described for the incorporation of multiple amino groups into oligonucleotides.202The oligonucleotide assembly requires the use of tert-butyl hydroperoxide as oxidising reagent. An alternative reagent for the synthesis of 5'-thiol containing oligonucleotideshas been described.203The phosphoramidite reagents (213a) and (213b) were synthesised from bromohexanol and potassium thioacetate or thiobenzoate in the presence of 18-crown-6, followed by subsequent phosphitylation. The thiol protecting group is removed during ammonia treatment.

An oligonucleotide with a 5'-ferrocene moiety and a 3'-thiol group has been prepared using the ferrocene linker reagent (214) in the last round of oligonucleotide synthesis.204The oligonucleotide was used to prepare a redox-active monolayer on gold.

(213) a; R = Me b; R = P h

225

5: Nucleotides and Nucleic Aci&

6

Interactions and Reactions of Nucleic Acids with Small Molecules

A series of 2,6-disubstituted amidoanthraquinones and 1,6disubstituted amidoanthraquinones have been synthesised and tested for their ability to stabilise triplex structures.205The former but not the latter series of compounds had been predicted to be effective in this regard by computer modelling studies. This was confirmed experimentally. In addition the type of substituent on the 2,6disubstituted amidoanthraquinones was found not to influence the ability to afford stabilisation of the triplex. A series of benzopyridoindole derivatives have been synthesised and shown to bind to triplex structures thus stabilising th~.206.207 McLaughlin and co-workers have attached the drug Hoechst 33258 to the 5’end of an oligonucleotide via a hex(ethy1ene glycol) linker.208When used as the third strand in triplex formation stabilisation of the triple helix was obtained. The potent anticancer drug daunorubicin has been cross-linked to DNA using formaldehyde. The 2-amino group of guanosine and the 3’-NH2 group the drug are both required for the linking reaction to take place.209 A polyamide which sequence specfically recognises the minor groove of DNA has been demonstrated to bind simultaneouslywith the third strand of a triplex in the major groove of DNA although no co-operativity of binding was observed.210 The stabilisation of triple helices by oligopeptideshas been studied.21 Pentalysine was the most effective at triplex stabilisation. The enantioselective intercalation of DNA by Rh-(~hen)~phi~+ isomers has been studied by NMRe212Electron transfer between R~(bpy)3~+ and guanine in DNA has been used as a measure of the solvent accessibility of n u c l e ~ b a s e s . ~ ~ ~ Interaction of the synthetic porphyrin H2FTMPP (215) with DNA duplexes and triplexes has been found to cause a stabilisation of Watson-Crick base pairs Me

Me

226

Organophosphorus Chemistry

but a destabilisation of Hoogsteen base pairs. The compound may therefore be useful in distinguishing between the two types of DNA architecture. Intrastrand cross-linking of the nitrogen mustard mechloethamine (216) has been observed and the products released after acid hydrolysis have been characterised and found to have the structure (217).214

The catalysis of DNA cleavage by metal complexes continues to be of interest. Reports of DNA cleavage by lanthanide complexes and cobalt(II1) complexes have appeared this year.215*216 The chemistry of platinum antitumor agents has been reviewed.217 7

Determination of Nucleic Acid Structures

The structure of the major photoproduct of irradiation of the dinucleotide d(TpA) and TA containing oligonucleotides has been re-characterised.21* 2’-Deoxyoxoanosine (218) has been isolated from calf thymus DNA after treatment with the mutagens nitrous acid or nitric oxide.*19 0 II

HO

The structural basis of phosphoramide mustard crosslinking to guanosines in an oligonucleotide has been studied both in vitro and by computer simulation.220 The effects of 5-fluorouridine and 5-fluoro-2’-deoxyuridine substitution into synthetic RNA and DNA have been studied. Destabilisation of duplex oligodeoxynucleotides but stabilisation of oligoribonucleotides was found upon the analogue substitution for uridine in the parent duplexes.221 The role of dihydrouridine in RNA structures has been examined by NMR spectroscopy. It was found that the dihydro derivative introduced greater conformational flexibility to the RNA by promoting the C2’-endo sugar con-

5: Nucleotides and Nucleic Acidr

227

formation.222The solution structure of an oligonucleotide containing an aminofluorene C8-modified-2’-deoxyguanosine has been solved. The aminofluorene ring is intercalated into the duplex and an unpaired adenine is looped out of the duplex.223 Jones and co-workers have used ”N7-labelled 2’-deoxyguanosine and 2’deoxyadenosine incorporated into a synthetic oligonucleotide triplex stucture to study the hydrogen bonding at these sites. Hoogsteen hydrogen bonding to the N7 purine atoms was observed.224 Jovin and Jareserijman have used fluorescence resonance energy transfer to determine the helical handedness, twist and rise of different DNA conformat i o n ~The . ~ technique ~~ relies on the attachment of two fluorescent dyes, a donor and an acceptor, to the DNA. Reagents which sequence specifically modify DNA and RNA are of interest in structural and footprinting studies. Co(I1) complexes in conjunction with KHSOs produce a guanine specific reaction which is sensitive to exposure of the face of the purine ring.226 A DNA molecule which binds to a N-methylmesoporphyrin has been evolved by in vitro selection techniques.227 The technique of X-ray crystallography is of great interest in the RNA area, where in comparison to DNA, very few structures currently exist. A sequence variation strategy for crystallising RNA motifs has been described228along with a method of large scale enzymatic synthesis of RNA for crystallography studies.229 The crystal structure of an RNA duplex has been resolved to very high resolution enabling a detailed look at the hydration of the RNA.230Water was bound in an ordered fashion in both the major and minor groove and the 2’-hydroxyl groups were found to scaffold the water arrangement in the latter groove. The X-ray crystal structure of an oligonucleotide containing four 4-thio-2’deoxythymidine nucleotides has been solved.231The modification confers nuclease resistance to oligodeoxynucleotides. A set of geometric parameters for the nitrogenous bases of DNA has been The data was collected from a statistical survey of the Cambridge Structural Database and will serve as target values for refinements of oligonucleotide structures. Scanning force microscopy has been used to visualise plasmid DNA which has been attached to mica using a magnesium(I1) containing The metal ions induce cross bridges between the mica and DNA phosphates thus immobolising the sample. Supercoiled and nicked DNA were observed. Scanning tunnelling microscopy of a 6-mercapto hexyl -oligonucleotide immobolised on a gold surface has been used to examined a bulged oligonucleotide. The bulge was seen to induce a 90 degree bend in the DNA.234 The mass spectrometry of oligonucleotides is a rapidly expanding research area dominated by the techniques of electrospray ionisation and matrix assisted laser desorption-ionisation, time of flight (MALDI-TOF) mass spectrometry. A number of reviews of this area have been published this year.23s-241Several

Organophosphorus Chemistry

228

matrices have been suggested for use with oligonucleotides including 4-hydroxy3-methoxyphenylpyruvic acid, indole-3-pyruvic acid, indole-3-glyoxylic acid,242 2,3,4-trihydroxyacetopheneone,2,4,6-trihydro~yacetophenone~~~ and sinapinic acid.244Methodologies have been developed for the sequencing of oligonucleotides using MALDI-TOF:45-251 including the sequence analysis of phosphorothioate containing DNA.252The effect of salts253*254 in mass spectrometry has been studied. MALDI-TOF has been used to assess the purity of synthetic DNA,255-257examine electrophore labelled DNA258and to analyse modified RNA and DNA.251*259*260 The products of reactions of DNA with platinating reagents have been studied by MALDI-TOF and a kinetic analysis has been possible.261 Duplex DNA263 can be observed by MALDI-TOF whereas duplex probes immobilised on streptavidin by a biotin linker allows observation of only the immobilised strand.264Non covalent complexes with proteins have also been observed.265Products of the polymerase chain and the ligase chain reactions have also been analysed using this technique.266-268 The covalent interactions of small molecules with DNA have also been studied using e l e c t r ~ s p r a yThe . ~ ~ ~use of liquid chromatography in conjunction with electrospray has been reviewed.270The use of electrospray in conjunction with capillary electrophoresis has also been investigated.271The stabilities of duplexes formed from 3’3’ - and 2’3’linked DNA have been compared by electrospray.272The binding of metal ions to oligonucleotides has also been studied using electrospray ionisation,Fourier transform ion cyclotron mass spectrometry .273 p262

References 1. 2.

3. 4. 5.

6. 7. 8. 9. 10. 11. 12.

C. McGuigan, D. Cahard, H. M. Sheeka, E. Declercq, and J. Balzarini,Biourg. Med. Chem. Lett., 1996,6, 1183-1186. C. McGuigan, D. Cahard, H. M. Sheeka, E. Declercq, and J. Balzarini, J. Med. Chem., 1996,39,1748-1753. J. L. Girardet, C. Perigaud, A. M. Aubertin, G. Gosselin, A. Kim, and J. L. Imbach, Bioorg. Med Chem. Lett., 1995,5,2981-2984. C. Meier, Angew. Chem. Int. Ed Engl., 1996,35,70-72. J. Balzarini, 0. Wedgwood, J. Kruining, H. Pelemans, R. Heijtink, E. Declercq, and C. McGuigan, Biochem. Biophys. Res. Commun., 1996,225,363-369. G. T. Morin and B. D. Smith, Tetrahedron Lett., 1996,37,3101-3104. K. M. Fries, C. Joswig,and R. F. Borch, J. Med Chem., 1995,38,2672-2680. S . Shuto, H. Awano, N. Shimazaki, K. Hanaoka, and A. Matsuda, Bioorg. Med. Chem. Lett., 1996,6,1021-1024. H. Sigmund and W. Pfeiderer, Helv. Chzh Actu, 1996,79,426-438. P. Mirelis and R. Brossmer, Bioorg. Med Chem. Lett., 1995,5,2809-2814. L. Schmitt and C. A. Caperelli, Nucleosides & Nucleotides, 1995, 14, 1929-1945. M. Sakurai, P. Wirsching, and K.D. Janda, Bioorg. Med Chem. Lett., 1996, 6, 1055-1060.

13. 14. 15. 16.

P. Lipka, A. Zatorski, K.A. Watanabe, and K.W. Pankiewicz, Nucleosides & Nucleotides, 1996,15, 149-167. R. Vince and P. T. Pham, Nucleosides & Nucleotides, 1995,14,2051-2060. X . H. Liu and C. B. Reesc, J. Chem. SOC.Perkin I , 1995,1685-1694. M . Ora, M. Oivanen, and H. Lonnberg, J. Chem. Suc. Perkin 2,1996,771-774.

5: Nucleotides and Nucleic Acids

17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41.

42. 43. 44.

45. 46. 47. 48. 49. 50.

51.

229

A. Kers, I. Kers, A. Kraszewski, M. Sobkowski, T. Szabo, M. Thelin, R. Zain, and J. Stawinski, Nucleosides & Nucleotides, 1996,15,361-378. N. N. Bhongle and J. Y .Tang, TetrahedronLett., 1995,36,6803-6806. R. Zain, R. Stromberg, and J. Stawinski,J. Org. Chem., 1995,60,8241-8244. R. Zain and J. Stawinski, J. Chem. Soc. Perkin 2,1996,795-799. E. Rozners, R. Stromberg, and E. Bizdena, Nucleosides & Nucleotides, 1995, 14, 851-853. W. Y.Lau, L.H. Zhang, J. W. Wang, D. L.Cheng, and K. Zhao,TetrahedronLett., 1996,37,4297-4300. M. C. Pirrung and N. Chidambaram, J. Org. Chem., 1996,61,1540-1542. S . G. Levy, D. B. Wasson, D. A. Carson, and H. B. Cottam, Synthesis-Stuttgart, 1996,843. R. E. Austin and D. G. Cleary, Nucleosides & Nucleotides, 1995,14,1803-1809. W. L. McEldoon and D. F. Wiemer, Tetrahedron, 1995,51,7131-7148. S . Freeman and J. M. Gardiner, Molecular Biotechnology, 1996,5,125-137. A. Holy and M. Masojidkova, Coll. Czech. Chem. Comm., 1995,60,1196-1212. A. Holy, H. Dvorakova, and M. Masojidkova, Coll. Czech. Chern. Comm., 1995,60, 1390- 1409. H. Dvorakova, M. Masojidkova, A. Holy, J. Balzarini, G.Andrei, R. Snoeck, and E. Declercq, J. Med Chem., 1996,39,3263-3268. K. Bednarski, D. M. Dixit, T. S. Mansour, S. G. Colman, S. M. Walcott, and C. Ashman, Bioorg. Med. Chem. Lett., 1995,5, 1741-1744. C. Meier, L. W. Habel, J. Balzarini, and E. Declercq, Liebigs Annalen, 1995, 2195-2202. C. Meier, L. W. Habel, J. Balzarini, and E. Declercq, Liebigs Annalen, 1995, 2203-2208. A. Routledge, I. Walker, S. Freeman, A. Hay, and N. Mahmood, Nucleosides & Nucleotides, 1995,14, 1545-1558. M. Oivanen, M. Ora, H.Almer, R. Stromberg, and H. Lonnberg, J. Org. Chem., 1995,60,5620-5627. A. P. Higson, G. K. Scott, D. J. Earnshaw, A. D. Baxter, R. A. Taylor, and R. Cosstick, Tetrahedron, 1996,52,1027-1034. G. H. Hakimelahi, A. A. Moosavimovahedi, M. M. Sadeghl, S. C. Tsay, and J. R. Hwu, J. Med Chem., 1995,38,4648-4659. C. Lebec and E. Wickstrom, J. Org. Chem., 1996,61,510-513. W. Dabkowski, I. Tworowska, and R. Saiakhov, Tetrahedron Lett., 1995, 36, 9223-9224. M. Bollmark, R. Zain, and J. Stawinski, TetrahedronLett., 1996,37,3537-3540. J. Cieslak, H. Sobkowski, A. Kraszewski, and J. Stawinski, Tetrahedron Lett., 1996, 37,4561-4564. R. W. Fischer and M. H. Caruthers, TetrahedronLett., 1995,36,6807-6810. F. J. ZhangandC. J. Sih, Bioorg. Med. Chem. Lett., 1995,5,1701-1706. F. J. Zhang, Q. M. Gu, P. C. Jing, and C. J. Sih, Bioorg. Med Chem. Lett., 1995,5, 2267-2272. K. Seio, T. Wada, K.Sakamoto, S. Yokoyama, and M. Sekine, Tetrahedron Lett., 1995,36,9515-9518. M. &a, M. Oivanen, and H. Lonnberg, J. Org. Chem., 1996,61,3951-3955. P. A. Heaton and F.Eckstein, Nucl. Aciab Res., 1996,24,850-853. J. Baraniak, W. J. Stec, and G. M. Blackburn, Tetrahedron Lett., 1995, 36, 81 19-8122. M. Endova, M. Masojidkova, M. Budesinsky, and I. Rosenberg, Tetrahedron Lett., 1996,37,3497-3500. J. R. Hwu, M. L. Jain, S. C. Tsay, and G. H. Hakimelahi, Chem. Comm., 1996, 545-546. M. J. Robins, S. Sarker, M. Q.Xie, W. J. Zhang, and M. A. Peterson, Tetrahedron Lett., 1996,37,3921-3924.

230

Organophosphorus Chemistry

52. 53. 54.

J. C.Zhang and M. D. Matteucci, Tetrahedron Lett. , 1995,36,8375-8378. Y.Ducharme and K. A. Harrison, Tetrahedron Lett., 1995,36,6643-6646. A. L. Roughton, S. Portmann, S. A. Benner, and M. Egli, J. Am. Chem. SOC.,1995, 117,7249-7250. J. Hall, P. Genschik, and W. Filipowicz, Helv. Chim. Actu, 1996,79,1005-1010. M.Zaccolo, D. M. Williams, D. M. Brown, and E. Gherardi, J. Mol. Biol., 1996, 255,589-603. T. Yamaguchi and M. Saneyoshi,Nucleosides & Nucleotides, 1996,15,607-618. J. Jansons, J. Stattel, A. Verri, J. Gambino, N. Khan, F. Focher, S. Spadari, and G. Wright, Nucleosides & Nucleotides, 1996,15,669-682. H. Li, K. Porter, F. Q. Huang, and B. R. Shaw, Nucl. Acids Res., 1995, 23, 4495-4501. P. Labataille, H. Pelicano, G. Maury, J. L. Imbach, and G. Gosselin, Bioorg. Med. Chem. Lett. , 1995,5,2315-2320. U.Wellmar, A. B. Hornfeldt, S. Gronowitz, and N. G. Johansson, Nucleosides & Nucleotides, 1996,15,1059-1076. R. H.Liu and L. E. Orgel, Nucl. Acids Res. , 1995,W,3742-3749. N.N. Bhongle and J. Y. Tang, Syn. Comm., 1995,25,3671-3679. A. Guzaev, H.Salo, A. Azhayev, and H. Lonnberg, Tetrahedron, 1995, 51, 93759384. C.Garciaechevarria and R. Haner, Tetrahedron, 1996,52,3933-3938. Z. D.Zhang and J. Y. Tang, Tetrahedron Lett., 1996,37,331-334. R. P. Iyer, D. Yu, T. Devlin, N. H.Ho, and S. Agrawal, J. Org. Chem., 1995,60, 5388-5389. S. G. Kim, K. Eida, and H. Takaku, Bioorg. Med. Chem. Lett., 1995,5,1663-1666. R. P. Iyer, Z. W. Jiang, D. Yu, W. T. Tan, and S . Agrawal, Syn. Comm., 1995,25, 361 1-3623. X.H.Zhang and R. A. Jones, Tetrahedron Lett., 1996,37,3789-3790. A. Routledge, M. P. Wallis, K. C. Ross, and W. Fraser, Bioorg. Med. Chem. Lett., 1995,5,2059-2064. E. Birchhirschfeld, Z. Foldespapp, K. H.Guhrs, and H. Seliger, Helv. Chim. Acta, 1996,79,137-150. E. Leikauf, F. Barnekow, and H.Koster, Tetrahedron, 1996,52,6913-6930. R. P. Iyer, T. Devlin, I. Habus, N. H. Ho, D. Yu, and S . Agrawal, Tetrahedron Lett. , 1996,37,1539-1542. R. P. Iyer, D. Yu, N. H. Ho, T.Devlin, and S. Agrawal, J. Org. Chem., 1995,60, 8132-8133. I. Habus, T. Devlin, R. P. Iyer, and S . Agrawal, Bioorg. Med. Chem. Lett., 1996,6, 1393-1398. M.C . Pirrung and J. C. Bradley, J. Org. Chem., 1995,60,6270-6276. H. Venkatesan and M. M. Greenberg, J. Org. Chem., 1996,61,525-529. D. K.Treiber and J. R. Williamson, Nucl. Acids Res., 1995,23,3603-3604. D. Y.Liu, S. L. Daubendiek, M. A. Zillman, K. Ryan, and E. T. Kool, J. Am. Chem. SOC., 1996,118,15871594. D.A. Lashkari, S. P.Hunickesmith, R. M. Norgren, R. W. Davis, and T. Brennan, Proc. Natl. Acad Sci., 1995,92,7912-7915. A. Ono, A. Matsuda, J. Zhao, and D. V. Santi, Nucl. Acids Res., 1995, 23, 4677-4682. F. Wincott, A. Direnzo, C. Shaffer, S. Grimm, D. Tracz, C. Workman, D. Sweedler, C. Gonzalez, S. Scaringe, and N. Usman, Nucl. Acids Res., 1995,23, 2677-2684. M. P. Reddy, F. Farooqui, and N. B. Hanna, Tetrahedron Lett., 1995, 36, 8929-8932. B. Mullah and A. Andrus, Nucleosides & Nucleotides, 1996,15,419-430. A. C.Anderson, S. A. Scaringe, B. E. Earp, and C. A. Frederick, RNA, 1996, 2, 11 0-1 1 7.

55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83.

84. 85. 86.

5: Nucleotides and Nucleic Acids

87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120.

23 1

D. Tsou, A. Hampel, A. Andrus, and R. Vinayak, Nucleosides & Nucleotides, 1995, 14, 1481- 1492. G. R. Gough, T. J. Miller, and N. A. Mantick, Tetrahedron Lett., 1996,37,981-982. S . L. Daubendiek, K. Ryan, and E. T . Kool, J. Am. Chem. Soc., 1995, 117, 7818-7819. A. Demesmaeker, K. H. Altmann, A. Waldner, and S . Wendebom, Cum. Op. Struc. Biol,, 1995,5,343-355. A. Demesmaeker,R. Haner, P. Martin, and H. E. Moser, Ace. Chem. Res., 1995,28, 366-374. W. J. Stec, A. Grajkowski, A. Kobylanska, B. Karwowski, M. Koziolkiewin, K. Misiura, A. Okruszek, A. Wilk, P. Guga, and M. Boczkowska, J Am. Chem. SOC.,1995,117,12019-12029. W.J. Stec, B. Karwowski, P. Guga, K. Misiura, M. Wieczorek, and J. Blaszczyk, Phosphorus Surfur and Silicon and the Related Elements, 1996,110,257-260. M. Mizuguchi and K. Makino, Nucleosides & Nucleotides, 1996,15,407-417. V. A. Efimov, A. L. Kalinkina, 0. G. Chakhmakhcheva, T. S. Hill, and K. Jayaraman, Nucl. Acids Res. , 1995,23,4029-4033. Q. H. Xu, K. Musierf'orsyth, R. P. Hammer, and G. Barany, Nucl. Acids Res., 1996, 24,1602-1607. V. T. Ravikumar, A. H. Krotz, and D. L. Cole, Tetrahedron Lett., 1995, 36, 65876590. K. L.Fearon, J. T. Stults, B. J. Bergot, L. M. Christensen, and A. M. Raible, Nucl. Acids Res. , 1995,23,2754-2761. W. T. Wiesler and M. H. Caruthers, J. Org. Chem., 1996,61,4272-4281. A. Okruszek, A. Sierzchala, K. L. Fearon, and W. J. Stec, J. Org. Chem., 1995,60, 6998-7005. A. B. Eldrup, J. Felding, J. Kehler, and 0. Dahl, Tetrahedron Lett., 1995, 36, 6127-6130. L. Wozniak, J. qZowski, and W.J. Stec, J. Org. Chem., 1996,61,879-881. R. G. Kuimelis and L. W.McLaughlin, Biochemistry, 1996,35,5308-5317. R. G. Kuimelis and L. W. McLaughlin, Nucl. Acids Res., 1995,23,4753-4760. R. G. Kuimelis and L. W. McLaughlin, J. Am. Chem. Soc., 1995,117,11019-11020. M. M. Vaghefi, R. C. Fazio, K. M. Young, and W.B. Marvin, Nucl. Acids Res., 1995,23,3600-3602. R. Fathi, W. Delaney, Q. Huang, and A. F. Cook, Nucleosides & Nucleotides, 1995, 14, 1725-1735. R. P. Iyer, T. Devlin, I. Habus, D. Yu, S. Johnson, and S . Agrawal, Tetrahedron Lett., 1996,37, 1543-1546. I. Tomoskozi, E. Gacsbaitz, and L. Otvos, Tetrahedron, 1995,51,6797-6804. J. K. Chen, R. G. Schultz, D. H. Lloyd, and S . M. Gryaznov, Nucl. Acb3 Res., 1995, 23,2661-2668. D. Y. Ding, S. M. Gryaznov, D. H. Lloyd, S. Chandrasekaran, S. J. Yao, L. Ratmeyer, Y. Q.Pan, and W.D. Wilson, Nucl. Acidr Res., 1996,24,354-360. F. Bergmann, W.Bannwarth, and S . Tam, Tetrahedron Lett. , 1995,36,6823-6826. U.Diederichsen,Angew. Chem. Int. Ed. Engl., 1996,35,445-448. U. Diederichsen and H. W. Schmitt, Tetrahedron Lett., 1996,37,475-478. A. H. Krotz, 0.Buchardt, and P. E. Nielsen, Tetrahedron Lett., 1995,36,6941-6944. A. H. Krotz, 0. Buchardt, and P. E. Nielsen, Tetrahedron Lett., 1995,36,6937-6940. D. W. Will, D. Langner, J. Knolle, and E. Uhlmann, Tetrahedron, 1995,51, 1206912082. K. H. Petersen, 0. Buchard, and P. E. Nielsen, Bioorg. Med. Chem. Lett., 1996, 6, 793-796. H. Umemiya, H. Kagechika, Y, Hashimoto, and K. Shudo, Nucleosides & Nucleotides, 1996,15,465-475. F. Morvan, Y. S. Sanghvi, M.Perbost, J. J. Vasseur, and L. Bellon, J. Am. Chem. SOC.,1996,118,255-256.

232

Organophosphorus Chemistry

121. T.Wada and M. Sekine, Tetrahedron Lett., 1995,36,8845-8848. 122. M.J. Damha, B. Meng, D. G. Wang, C. G. Yannopoulos, and G. Just, Nucl. Acids Res., 1995,23,3967-3973. 123. G. Stork, C. Z. Zhang, S. Gryaznov, and R. Schultz, Tetrahedron Lett., 1995, 36, 6387-6390. 124. G. Viswanadham, G. V. Petersen, and J. Wengel, Bioorg. Med. Chem. Lett., 1996,6, 987-990. 125. S. Obika, Y. Takashima, Y. Matsumoto, K. Kuromaru, and T. Imanishi, Tetrahedron Lett., 1995,36,8617-8620. 126. S . Obika, Y. Takashima, Y. Matsumoto, A. Shimoyama, Y.Koishihara, Y.Ohsugi, T. Doi, and T. Imanishi, Bioorg. Med. Chem. Lett., 1996,6, 1357-1360. 127. E. Larsen, K. Danel, and E. B. Pedersen, Nucleosides & Nucleotides, 1995, 14, 1905-1912. 128. C. Richert, A. L. Roughton, and S. A. Benner, J. Am. Chem. SOC., 1996, 118, 4518-4531. 129. R. M. Zou and M. D. Matteucci, Tetrahedron Lett., 1996,37,941-944. 130. I. Barber, G. Tosquellas, F. Morvan, B. Rayner, and J. L. Imbach, Bioorg. Med Chem. Lett., 1995,5, 1441-1444. 131. G. Tosquellas, I. Barber, F. Morvan, B. Rayner, and J. L. Imbach, Bioorg. Med. Chem. Lett., 1996,6,457-462. 132. 2. D. Zhang, J. X. Tang, and J. Y . Tang, Bioorg. Med. Chem. Lett., 1995, 5, 1735-1740. 133. C. L. Scremin, J. H. Boal, A. Wilk, L. R. Phillips, L. Zhou, and S . L. Beaucage, Tetrahedron Lett., 1995,36,8953-8956. 134. C. L. Scremin, J. H. Boal, A. Wilk, L.R. Phillips, and S . L. Beaucage, Bioorg. Med. Chem. Lett., 1996,6,207-212. 135. C. Chaix, R. P. Iyer, and S . Agrawal, Bioorg. Med. Chem. Lett., 1996,6,827-832. 136. C . Horndler and W. Pfleiderer, Helv. Chh. Acta, 1996,79,718-726. 137. L. Beigelman, A. Karpeisky, J. Matulicadamic, P. Haeberli, D. Sweedler, and N. Usman, Nucl. Acids Res., 1995,23,4434-4442. 138. N. N. Polushin, I. P. Smirnov, A. N. Verentchikov, and J. M. Coull, Tetrahedron Lett., 1996,37,3227-3230. 139. G. Wang and P. J. Middleton, Tetrahedron Lett., 1996,37,2739-2742. 140. H. Thrane, J. Fensholdt, M. Regner, and J. Wengel, Tetrahedron, 1995, 51, 10389-10402. 141. K.D. Nielsen, F. Kirpekar, P. Roepstorff, and J. Wengel, Bioorg. Med Chem, 1995, 3, 1493-1502. 142. B. Doboszewski, H. Dewinter, A. Vanaerschot, and P. Herdewijn, Tetrahedron, 1995,51,12319-12336. 143. J. Wengel, M. L. Svendsen, P. N. Jorgensen, and C. Nielsen, Nucleosides & Nucleotides, 1995,14, 1465-1479. 144. J. C. Litten and C. Leumann, Helv. Chim. Acta, 1996,79, 1129-1146. 145. K. Yamana, T. Mitsui, J. Yoshioka, T. Isuno, and H. Nakano, Bioconjugate Chemistry, 1996,7,715-720. 146. K. Yamana, A. Yoshikawa, and H. Nakano, Tetrahedron Lett., 1996,37,637-640. 147. E. I. Kvasyuk, T. 1. Kulak,I. A. Mikhailopulo, R. Charubala, and W. Pfleiderer, Helv. Chim. Acta, 1995,78, 1777-1784. 148. M.Sekine, H.Tsuruoka, S. Iimura, H. Kusuoku, T.Wada, and K. Furwawa, J. Org. Chem., 1996,61,4087-4100. 149. Y. Z . Xu, V. Ramesh, and P. F. Swann, Bioorg. Med. Chem. Lett., 1996, 6, 1179-1182. 150. H. Kuhn, D. P. Smith, and S.S. David, J. Org. Chem., 1995,60,7094-7095. 151. R. G. Eason, D. M. Burkhardt, S. J. Phillips, D. P. Smith, and S . S . David, Nucl. Acids Rex, 1996,24,890-897. 152. M . Acedo, E. Declercq, and R. Eritja, J. Org. Chem., 1995,60,6262-6269. 153. F. Seela and Y. M. Chen, Nucl. Acids Res., 1995,23,2499-2505.

5: Nucleotides and Nucleic Acidr

154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186.

233

D. G. Wang and P. 0 .P. Tso, Nucleosides & Nucleotides, 1996,15,387-397. F. Seela, N. Ramzaeva, and Y . M. Chen, Bioorg. Med Chem. Lett., 1995, 5, 3049-3052. E. Ferrer, C. Fabrega, R. G. Garcia, F. Azorin, and R. Eritja, Nucleosides & Nucleotides, 1996,15,907-921. D. Loakes, D. M. Brown, S. Linde, and F. Hill, Nucl. Acidr Res., 1995, 23, 2361-2366. A. Vanaerschot, J. Rozenski, D. Loakes, N. Pillet, G. Schepers, and P. Herdewijn, Nucl. Acidr Res., 1995,23,4363-4370. J. Michel, J. J. Toulme, J. Vercauteren, and S . Moreau, Nucl. AcidF Res., 1996, 24, 1127-1135. C. Y.Huang, G. X. Bi, and P. S . Miller, Nucl. A c i h Res., 1996,24,2606-2613. G. B. Xiang, R. Bogacki, and L. W. McLaughlin, Nucl. Acidr Res., 1996, 24, 1963-1970. R. Berressem and J. W. Engels, Nucl. Acids Res., 1995,23,3465-3472. F. Raynaud, U. Asseline, V. Roig, and N. T . Thuong, Tetrahedron, 1996, 52, 2047-2064. S.Baillet and J. P. Behr, Tetrahedron Lett., 1995,36,8981-8984. M. E. Hawkins, W. Pfleiderer, A. Mazumder, Y.G. Pommier, and F. M. Falls, Nucl. Acids Res., 1995,23,2872-2880. J. Schliepe, U. Berghoff, B. Lippert, and D. Cech, Angew. Chem. Int. Ed. Engl., 1996,35,646-648. C. J. Adams, J. B. Murray, M. A. Farrow, J. R. P. Arnold, and P. G. Stockley, Tetrahedron Lett., 1995,36,5421-5424. A. Fischer, Z. Gdaniec, E. Biala, M. Lozynski, J. Milecki, and R. W.Adamiak, Nucleosides & Nucleotides, 1996,15,477-488. M. Sekine, M. Kadokura, T. Satoh, K. Seio, T.Wada, U. Fischer, V. Sumpter, and R. Luhrmann, J. Org. Chem., 1996,61,4412-4422. I. A. Mikhailopoulo, E. N. Kalinichenko, T. L. Podkopaeva, T. Wenzel, H. Rosemeyer, and F.Seela, Nucleosides & Nucleotides, 1996,15,445-464. M. K. Herrlein, J. S. Nelson, and R. L. Letsinger, J. Am. Chem. SOC.,1995, 117, 10151-10152. K. Schutz, M. Kurz, and M. W. Gobel, Tetrahedron Lett., 1995,36, 8407-8410. S. Akhtar, A. Routledge, R. Patel, and J. M. Gardiner, Tetrahedron Left., 1995,36, 7333-7336. H. Ozaki, A. Nakamura, M. Arai, M. Endo, and H. Sawai, Bull. Chem. Soc. Japan, 1995,68,1981-1987. C . Switzer,T.P. Prakash, and Y .Ahn, Bioorg. Med. Chem. Lett., 1996,6,815-818. R. L. Letsinger and T. F. Wu, J. Am. Chem. Soc., 1995,117,7323-7328. J. S. Nelson, L. Giver, A. D. Ellington, and R. L. Letsinger, Biochemistry, 1996,35, 5339-5344. S . Altmann, A. M. Labhardt, D. Bur, C. Lehmann, W. Bannwarth, M. Billeter, K. Wuthrich, and W. Leupin, Nucl. Acids Res., 1995,23,4827-4835. N. C . Chaudhuri and E. T. Kool, J. Am. Chem. Soc., 1995,117,10434-10442. K. J. Percival and C. W. G. Fishwick, Nucleosides & Nucleotides, 1995, 14, 1785-1794. D. Tsarouhtsis, S. Kuchimanchi, B. L. Decorte, C. M. Harris, and T. M. Harris, J. Am. C h m . SOL,1995,117,11013-11014. R. S.Coleman and E. A. Kesicki, J. Org. Chem., 1995,60,6252-6253. S. I. Antsypovich, T. S. Oretskaya, E. M. Volkov, E. A. Romanova, V. N. Tashlitsky, M. Blumenfeld, and Z . A. Shabarova, Nucleosides & Nucleotides, 1996, 15,923-936. J. Olejnik, E. Knymanskaolejnik, and K. J. Rothschild, Nucl. Acidr Res., 1996,24, 361-366. D. L. McMinn and M. M. Greenberg, Tetrahedron, 1996,52,3827-3840. P. Neuner, Bioorg. Med Chem. Lett., 1996,6,147-152.

234

Organophosphorus Chemktry

187.

B. P. Zhao, G. B. Panigrahi, P. D. Sadowski, and J. I. Krepinsky, TetrahedronLett.,

188.

A. Peyman, C. Weiser, and E. Uhlmann, Bioorg. Med. Chem. Lett., 1995, 5,

1996,37,3093-3096. 2469-2472. 189.

M. A. Reynolds, T. A. Beck, P. B. Say, D. A. Schwartz, B. P. Dwyer, W. J. Daily, M. M. Vaghefi, M. D. Metzler, R. E. Klem, and L. J. Arnold, Nucl. Acids Rex,

190. 191.

S.Basu and E. Wickstrom, Tetrahedron Lett. , 1995,36,4943-4946. J. C. Truffert, U. Asseline, N. T. Thuong, and A. Brack, Protein and Peptide Letters,

192. 193. 194. 195.

N. N. Polushin, Tetrahedron Lett., 1996,37,3231-3234. P. Bigey, G. Pratviel, and B. Meunier, Nucl. Acids Res.,1995,23,3894-3900. H. Ikeda, K. Fuji, and K. Tanaka, Bioorg. Med. Chem. Lett., 1996,6, 101-104. J. K.Bashkin, J. Xie, A. T. Daniher, U. Sampath, and J. L. F. Kao, J. Org. Chem.,

196.

199.

X . F. Ren, B. A. Schweitzer, C. J. Sheik, and E. T. Kool, Angew. Chem. Int. Ed. Engl., 1996,35,743-746. J. Matulicadamic, C. Gonzalez, N. Usman, and L. Beigelman, Bioorg. Med Chem. Lett., 1996,6,373-378. Y. Z. An, C. H. B. Chen, J. L. Anderson, D. S.Sigman, C. S.Foote, and Y. Rubin, Tetrahedron,1996,52,5179-5189. T. Delumleywoodyear, C. N. Campbell, and A. Heller, J. Am. Chem. Soc., 1996,

200.

A. Bidaine, C. Berens, and E. Sonveaux, Bioorg. Med Chem. Lett., 1996, 6,

201.

203.

I. A. Prokhorenko, V. A. Korshun, A. A. Petrov, S. V. Gontarev, and Y. A. Berlin, Bioorg. Med Chem. Lett., 1995,5,2081-2084. C. Behrens, K. H. Petersen, M. Egholm, J. Nielsen, 0. Buchardt, and 0. Dahl, Bioorg. Med Chem. Lett., 1995,5,1785-1790. P. Kumar, D. Bhatia, R. C. Rastogi, and K. C. Gupta, Bioorg. Med. Chem. Lett.,

204.

R. C. Mucic, M. K. Herrlein, C. A. Mirkin, and R. L. Letsinger, Chem. Comm.,

205.

K. R. Fox, P. Polucci, T. C. Jenkins, and S . Neidle, Proc. Natl. Acud Sci., 1995,92,

206.

C. Escude, S. Mohammadi, J. S. Sun, C. H. Nguyen, E. Bisagni, J. Liquier, E. Taillandier,T. Garestier, and C . Helene, Chemistry & Biology, 1996,3, 57-65. C . Escude, C. H.Nguyen, J. L. Mergny, J. S. Sun, E. Bisagni, T. Garestier, and C. Helene, J. Am. Chem. SOC., 1995,117,10212-10219. J. Robles, S. B. Rajur, and L. W. McLaughlin, J. Am. Chem. Soc., 1996, 118,

1996,24,760-765. 1995,2,419-424.

1996,61,2314-2321. 197. 198.

118,5504-5505. 1167- 1170. 202.

1996,6,683-688. 1996,555-557. 7887-7891. 207. 208.

5820-5821. 209. 210. 211. 212. 213.

F. F. Leng, R. Savkur, I. Fokt, T. Przewloka, W. Priebe, and J. B. Chaires, J. Am. Chem. SOC., 1996,118,473 1-4738. M. E.Parks and P. B. Dervan, Bioorg. Med Chem., 1996,4, 1045-1050. V.N. Potaman and R. R. Sinden, Biochemistry, 1995,34,14885-14892. T. P. Shields and J. K. Barton, Biochemistry, 1995,34,15049-15056. D. H.Johnston, K. C. Glasgow, and H. H.Thorp, J. Am. Chem. SOC.,1995, 117, 8933-8938.

214. 215.

S. M. Rink and P. B. Hopkins, Biuorg. Med. Chem. Lett., 1995,5,2845-2850. J. Rammo, R. Hettich, A. Roigk, and H. J. Schneider, Chem. Comm., 1996, 105- 107.

216. 217. 218.

N. E.Dixon, R. J. Geue, J. N. Lambert, S. Moghaddas, D. A. Pearce, and A. M. Sargeson, Chem. C u m . , 1996,1287-1288. J. Reedijk, Chem. Comm., 1996,801-806. X . D. Zhao, S. Nadji, J. L. F. Kao, and J. S. Taylor, Nucl. Acids Rex, 1996, 24, 1554-1560.

5: Nucleotides and Nucleic A c i h

235

219.

T. Suzuki, R. Yamaoka, M. Nishi, H. Ide, and K. Makino, J. Am. Chem. SOC.,1996,

220.

Q. Dong, D. Barsky, M. E. Colvin, C. F. Melius, S. M. Ludeman, J. F. Moravek, 0. M. Colvin, D. D. Bigner, P. Modrich, and H. S . Friedman, Proc. Natl. Acad. Sci.,

221.

P. V. Sahasrabudhe, R. T. Pon, and W. H. Gmeiner, Nucl. AcirIs Res., 1995, 23,

222. 223.

J. J. Dalluge, T. Hashizume, A. E. Sopchik, J. A. McCloskey, and D. R. Davis, Nucl, A c i h Res., 1996,24, 1073-1079. B. Mao, B. E. Hingerty, S. Broyde, and D. J. Patel, Biochemistry, 1995, 34,

224.

B. L. Gaffney, P. P. Kung, C. Wang, and R. A. Jones, J. Am. Chem. SOC.,1995,117,

225. 226.

E. A. Jareserijman and T. M. Jovin, J. Mol. Biol., 1996,257,597-617. J. G. Muller, P. Zheng, S. E. Rokita, and C. J. Burrows, J. Am. Chem. SOC.,1996,

227. 228. 229.

Y. F. Li, C. R. Geyer, and D. Sen, Biochemistry, 1996,35,6911-6922. A. C. Anderson, B. E. Earp, and C. A. Frederick, J. Mol. Biol., 1996,259,696-703. S . R. Price, N. Ito, C. Oubridge, J. M. Avis, and K. Nagai, J. Mol. Biol., 1995,249,

118,251 5-2516. 1995,92, 12170-12174. 3916-3921.

-

16641 16653. 12281-12283. 118,2320-2325.

398-408.

234.

M. Egli, S.Portmann, and N. Usman, Biochemistry, 1996,35,8489-8494. T. J. Boggon, E. L. Hancox, K. E. McAuleyhecht, B. A. Connolly, W. N. Hunter, T. Brown, R. T. Walker, and G. A. Leonard, Nucl. Acids Rex, 1996,24,951-961. L. Clowney, S. C. Jain, A. R. Srinivasan, J. Westbrook, W. K. Olson, and H. M. Berman, J. Am. Chem. SOC.,1996,118,509-518. B. Samori, C. Nigro, A. Gordano, I. Muzzalupo, and C. Quagliariello, Angew. Chem. In?. Ed. Engl., 1996,354 529-530. D. Rekesh, Y.Lyubchenko, L. S. Shlyakhtenko, and S . M. Lindsay, Biophys. J.,

235.

J. P. Barry, P.Vouros, A. Vanschepdael, and S. J. Law, J. Mass. Spec., 1995, 30,

236.

993-1006. M. C. Fitzgerald and L. M. Smith, Ann. Rev. Biophys. Biomol. Structure, 1995, 24, 117-140.

237.

C. R. Iden, R. A. Rieger, M. C. Torres, and L. B. Martin, ACS Symposium Series,

238.

P. Juhasz, M. T. Roskey, I. P. Smirnov, L. A. Haff, M. L. Vestal, and S.A. Martin, Anal. Chem., 1996,68,941-946. R. Kaufmann, J. Biotech., 1995,41, 155-175. E. Nordhoff, Trac-Trendr In Analytical Chemistry, 1996,15,240-250. V. M. Orlov, V. N. Pustobaev, and R. N. Maslova, Molecular Biology, 1996, 30,

230. 231. 232. 233.

1996,71,1079-1086.

1996,619,281-293. 239. 240. 241.

444-452. 242. 243. 244.

J. Bai, X. L. Liang, Y. H. Lin, Y.D. Zhu, and D. M. Lubman, Rapid Commun. Mass Spectrom., 1996,10,839-844. Y. F. Zhu, C. N. Chung, N. I. Taranenko, S. L. Allman, S. A. Martin, L. Haff, and C. H. Chen, Rapid Commun. Mass Spectrom., 1996,10,383-388. T. Kosaka, T.Kinoshita, and M. Takayama, Rapid Commun. Mass Spectrom., 1996, 10,405-408.

245. 246. 247. 248. 249.

L. A. Haff and I. P. Smirnov, Biochemical Society Transactions, 1996,24,901-904. H. Koster, K. Tang, D. J. Fu, A. Braun, D. Vandenboom, C. L. Smith, R .J. Cotter, and C. R. Cantor, Nature Biotechnology, 1996,14,1123-1128. E. Nordhoff, M. Karas, R. Cramer, S. Hahner, F. Hillenkamp, F. Kirpekar, A. Lxzius, J. Muth, C. Meier, and J. W. Engels, J. Mass. Spec., 1995,30,99-112. M. T. Roskey, P. Juhasz, I. P. Smirnov, E. J. Takach, S. A. Martin, and L. A. Haff, Proc. Natl. Acad Sci., 1996,93,4724-4729. I. P. Smirnov, M. T.Roskey, P. Juhasz, E. J. Takach, S. A. Martin, and L. A. Haff, Anal. Biochem., 1996,238, 19-25.

236

OrganophosphorusChemistry

250. 251. 252.

G. Talbo and M. Mann, Rapid Commun. Mass Spectrom., 1996,10,100-103. E. Gentil and J. Banoub, J. Mass.Spec., 1996,31,83-94. J. M. Schuette, U. Pieles, S. D. Maleknia, G. S. Srivatsa, D. L. Cole, H. E. Moser, and N. B. Afeyan, J. Phann. Biomed Anal., 1995,13,1195-1203. F. Dubois, R. Knochenmuss, R. J. J. M. Steenvoorden, K. Breuker, and R. Zenobi, European Mass Spectrometry, 1996,2, 167- 172. T. A. Shaler, J. N. Wickham, K. A. Sannes, K. J. Wu, and C. H.Becker, Anal. Chem., 1996,68,576-579. A. Deroussent, J. P. Lecaer, J. Rossier, and A. Gouyette, Rapid Commun. Mass Spectrom., 1995,9,1-4. D. M. Reddy and C. R. Iden, American Laboratory, 1995,27,15. N. P. Christian, S. M. Colby, E. Giver, C. T. Houston, R.J. Arnold, A. D. Ellington, and J. P. Reilly, Rapid Commun. Mass Spectrom., 1995,9,1061-1066. P. F. Britt, G. B. Hurst, and M. V. Buchanan, J. Muss. Spec., 1996,31,661-668. E. A. Stemmler, M. V. Buchanan, G. B. Hurst, and R. L. Hettich, Anal. Chem.,

253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273.

1995,67,2924-2930. J. A. Kowalak, E. Bruenger, T. Hashizume, J. M. Peltier, J. Ofengand, and J. A. McCloskey, Nucl. Acids Res., 1996,24,688-693. G. Lowe, J. A. McCloskey, J. S.Ni, and T. Vilaivan, Bioorg. Med Chem., 1996,4, 1007-1013. F. Gonnet, F. Kocher, J. C. Blais, G. Bolbach, J. C. Tabet, and J. C. Chottard, J. Mms. Spec,, 1996,31,802-809. P. Lecchi and L. K.Pannell, J. Am. Soc. Mars Spectrom., 1995,6,972-975. K. Tang, D. J. Fu, S. Kotter, R. J. Cotter, C. R. Cantor, and H. Koster, Nucl. Acidr Res., 1995,23,3126-3131. X . D. Tang, J. H. Callahan, P. Zhou, and A. Vertes, Anal. Chem., 1995, 67, 4542-4548. G. B. Hurst, M. J. Doktycz, A. A. Vass, and M. V. Buchanan, Rapid Commun. Mass Spectrom., 1996,10,377-382. C. Jurinke, D. Vandenboom, A. Jacob, K. Tang, R. Worl, and H. Koster, Anal. Biochem., 1996,237,174-181. N. 1. Taranenko, K. J. Matteson, C. N. Chung, Y. F. Zhu, L. Y.Chang, S. L. Allman, L. Haff, S. A. Martin, and C. H. Chen, Genetic Analysis-Biomolecular Engineering, 1996,13,87-94. G. Wickham, P. Iannitti, J. Boschenok, and M. M. Sheil, J. Mass. Spec., 1995, S 197-S 203. B. Bothner, K. Chatman, M. Sarkisian, and G. Siuzdak, Bioorg. Med Chem. Lett., 1995,5,2863-2868. J. P. Barry, J. Muth, S. J. Law, B. L. Karger, and P. Vouros, J. Chrom. A., 1996, 732,159-1 66. X . H. Cheng, Q.Y.Gao, R. D. Smith, K. E. Jung, and C. Switzer, Chem. Comm., 1996,747-748. Q. Y .Wu, X.H. Cheng, S.A. Hofstadler, and R. D. Smith, J. Mass. Spec., 1996,31, 669-675.

6 Ylides and Related Compounds BY B. J. WALKER

1

Introduction

Overall levels of innovation in the area this year are disappointingly low. All the various forms of phosphorus-based olefination continue to be used widely in synthesis and perhaps the relative paucity of new phosphorus chemistry is a reflection on the extent to which these methods have been developed. One area which does continue to develop, and where there is still considerable potential, is the use of phosphorus stabilised anions in enantioselective and asymmetric synthesis. Warren’s continuing use of phosphine oxides and Denmark’s excellent contributions to this area are especially worthy of mention. In volume 29 this chapter will, for the first time since volume 11, have a new author. Much of the ylide chemistry discussed in volume 11 would not be out of place in the current volume. In volume 28 an even wider application in synthesis, helped by improvements in available bases and other reagents and conditions, is apparent. A better understanding of mechanism, particularly of olefin synthesis, is available and this has enabled improved control of stereochemistry in all its forms, although improved stereo-control has also derived from a greater use of phosphonate and phosphine oxide anions. However, the opportunities offered by the enormous improvements in spectroscopic techniques, particularly NMR and mass spectrometry, and chiral and preparative HPLC and the increased demands of modern biology and medicine have perhaps had the greatest influence.

2

Methylenephospboranes

The chemistry of phosphonium salts, ylides and phosphoranes is covered in volume 3 of ‘The Chemistry of Organophosphorus Compounds’ series.’ 2.1 Preparation and Structure. - The equilibrium acidities and homolytic bond dissociation energies of a number of alkyltriphenylphosphonium salts (1) and the oxidation potentials of the corresponding ylides have been determined.* The triphenylphosphonium substituent lowers the pKa value of the a-hydrogens by approximately 25 units (142 kJmol-’) while the effect of the corresponding triphenylarsonium substituent is some 4 pK, units less. 237

238

Organophosphorus Chemistry

The unstable triethoxyphosphoranes(2) have been generated by the reaction of oxalylcarbamates with triethyl ph~sphite.~ Reaction of (2) in situ with bromotrimethylsilane or hydrogen bromide in acetic acid gave the corresponding phosphonates (3) in high yield and so provides a new and most convenient route to the synthetically useful amino(diethoxyphosphory1)-acetic esters (4) (Scheme 1). Trimethoxyphosphoranes (6) are among the products reported in new examples of reactions of the carbene intermediates (5).4 A re-investigation of the reaction of triphenylphosphine with isatin (7) has shown the previous reports to be incorrect and that the products are in fact the new phosphonium ylide (8) and isoindigo (9).5

ii

C02R

C02R

py :P(OEt)* : Cbz’ C02R

I

iii

0 il

H2NYP(oEt)2

Reagents: i, (EtO)3P,PhCH3,112 “C;ii, TMSBr or HBr/ AcOH, 10 “C; iii, H2, Pd/C, MeOH

Scheme 1

A variety of cyclic phosphonium ylide structures have been reported. Hetero-cyclic and -bicyclic structures, including the ylide (11) and a variety of iminophosphoranes, are the products of the reaction of the 1,2-dihydro-l,3,2diazaphosphinine (10) with dimethyl acetylenedicarboxylate.6 Attempts to prepare a simple adduct of DBN with the (phosphino)(P-chlorophosphonio) carbene (12) led instead to formation of the unsaturated tricyclic adduct (13).’ The diphosphete structure (14) is the product of a simple two component reaction of dichloro(bis(trimethylsily1)methylphosphine) with DBU.*Details of the synthesis, chemistry and structure of k5-phosphetes (19, benzo-h5-phosphetes (16), and naphtho-k’-phosphetes (17) have been r e p ~ r t e d2,4Diphosphoniodihydro.~ phosphetide cations (19) have been prepared by condensation of the 1,3-diphosphoniopropenide cation (18) with phosphorus (XII) dichlorides.10 In

6: Ylides and Related Compounds

+ Ph3P

239

R.T.

H

H

% N

'

,oHex N

(12) R = NP$2

(13)

240

Organophosphorus Chemistry

the presence of triphenylphosphine, which acts as a reducing agent, and excess phosphorus(II1) dichloride the reaction proceeds further to provide 3,5-diphosphoniodihydro-1,Zdiphospholide cations (20). The 1,2-dihalogenoderivative (20, Y=Cl) can be converted into the diphosphonio-1,2-diphospholide (21) by treatment with tributylphosphine. Diphosphaheterocycles(23) containing both pentacoordinate and tetracoordinate phosphorus atoms within the ring have been prepared for the first time by reaction of the 1,3-diphospha cation (22) with sodium HMDS." The structure of one example (23, R=Me) has been confirmed by X-ray analysis. Attempts to synthesise halophosphaalkeneylides (24) have led ultimately to oligomers, e.g., (25), (26), and (27).12 Structure (26) has been confirmed by X-ray analysis.

Ph3P+-CCH=CPhCH=PPhs

ypc'2 Et3N

Y

Ph3Pq P + P h 3 X-

X(18)

Ph (1 9)

YPCl2, Ph3P

y\

I Ph

'-

P

h

,y

3

P Ph

pP+Ph3 X-

6: Ylides and Related Compounlis

241

Threecoordinate ylide-type structures continue to be reported. Evidence has been presented that the fluorenylideneoxophosphorane(29) is an intermediate in the nucleophilic substitution reaction of the phosphonamidic chloride (28) with dieth~1amine.l~ The diphosphene (31) and the metaphosphonate (32) are thought to be intermediates in the reaction of diphosphene (30) with oxygen to give the novel 1,3-dio~o-2h~,43L~,SX~-triphospholane-2-oxide (33).14The first stable monomeric phosphorus monochalcogenides, e.g. (34), and dichalcogenides, e.g. (33, without bulky or intramolecular co-ordinating substituents have been prepared. Compounds (34) react with alkylidenephosphonium ylides to form 1,2,4-thia(or se1ena)diphosphetane monosulfides (or mono-selenides) (36). l6 The lithiated derivative (38), obtained from treatment of the bis(methy1ene)phosphorane (37) with n-butyllithium, can be considered as a carbenoid-lithium complex. An

-8 ,

Et2NH

\

0 I/ P,-NEtZ NEt2

242

Organophosphorus Chemistry

R’

(30) R

=y /p-p\

R

R’

Ap5x +

Ph3P=CR2R3

2 Ph3P

-

Ph3P? .> ,i

(34) X = S or Se

NHR

R’ R2

x

R3 R’

x

PAP,

h3

(36) X = S or Se

Li

I

extensive investigation of the structure of (38), including I3C and 31PNMR studies and a single crystal X-ray structure, has been carried out.” Lithiated iminophosphoranes, e.g. (39) and (40), have been prepared by the reaction of N-silyliminophosphoranes with n-butyllithium. l8 In several cases the structures have been determined by X-ray analysis. [LiCH2PMe2NSiMe3]4

[LiCMe2PPt$NSiMe&

(39)

2.2

(40)

Reactions of Methylenephosphoranes

2.2.1 Aldehydes. - The mechanism of the Wittig and related (see sections 3 and 4) olefination reactions continues to be studied. The Wittig reaction of

6: Ylides and Related Compounds

Ph3P=CH2

+ Ph2C=S

243

/

Ph3P-CH2

I

Ph3P=S

+ CH2ZCPh2

I

S-CPh2

/"\

(42)

Ph3P +H2C--CPh2

1-adamantylmethylenetriphenylphosphorane (41) with a range of substituted benzaldehydes has been investigated and the results compared with those obtained from similar reactions of butylidene- and isopropylidene- ylides.l9 3'P NMR studies of the reactions of (41) have allowed observation of the diastereomeric oxaphosphetane intermediates and their decomposition. The results of these experiments and other evidence, including p-values, have led the authors to conclude that an electron-transfer mechanism operates in the formation of the oxaphosphetanes from (41). A thiaphosphetane intermediate (42) in a reaction of a phosphonium ylide with a thioketone has been observed for the first time.20The identification of (42) as a thiaphosphetane rather than a betaine structure is based on 31P and 13C NMR, the latter carried out in experiments involving 13C labelled ylide and in one case 13Clabelled thioketone. The products from the decomposition of (42) depend on the reaction temperature. At -20 "C triphenylphosphine and 2,2-diphenylthiirane are slowly formed while at >O "C these products are converted into triphenylphosphine sulfide and 1,l -diphenylethene, presumably via the thiaphosphetane (42). 1,2-)LS-Azaphosphetidines, e.g. (44),which have the structure of the azaphosphetane intermediates in the am-Wittig reaction, have been prepared by treatment of the phosphine oxides, e.g. (43), with Mitsunobu's reagent.21 At 200°C (44)gave alkene and iminophosphorane (45).

Ph3P

(45)

(43) (44) \--I

+

Organophosphorus Chemistry

244

The rate of reaction of stabilised ylides with aldehydes in hexane is greatly enhanced when carried out in the presence of silica Due to the low solubility of triphenylphosphine oxide in hexane the procedure has the added advantage that a simple filtration through a pad of silica provides a pure product. High levels of stereo-control in the most studied of all Wittig reactions, stilbene formation, have been reported.23 Two-phase reactions in dichloromethane of aromatic aldehydes with substituted benzyltriphenylphosphonium salts (46) in the presence of 18-crown-6 using solid potassium hydroxide as base give very rapid, (2)-selective olefination even at - 70 "C.The extent of selectivity is dependent on the nature of the counter ion. Similar reactions using substituted benzylchlorodiphenylphosphonium salts (47) gave excellent (@-selectivity. An explanation of the results is offered in terms of the oxaphosphetane-like transition state in each case. L Ph2PCH2 +

(46) L = Ph (47) L = CI

2.2.2 Ketones. - A further example of difficulties encountered in Wittig methylenation reactions is the lack of alkene formation on reaction of methylenetriphenylphosphorane-LiBr complex with bis(pyridy1) ketone.% A similar reaction of the free ylide, generated by use of potassium t-butoxide as base, gave >go% yield of alkene and this result supports the author's explanation which involves formation of a stable chelated intermediate (48) in reactions in the presence of lithium bromide. During the synthesis of carbacyclin derivatives Wittig reactions of the bicyclic ketones (49) with ylides (51) derived from aalkanecarboxylateshave previously been reported to give (1:1) mixtures of (EZ)-

Ph3P+

6: YIides and Related Compoundr

245

isomers. However, it is now reported that the introduction of a sulfonamide function in place of the alkyl group, as in (SO), leads to highly stereoselective formation of the (Z)-i~omer.~' The results are tentatively explained through the interaction of the charges on the deprotonated sulfonamide and the electrophilic phosphorus atom of the ylide. 0

(49) R = Alkyl (50) R = CH2NHS02Ar

A number of vinyldiazomethanes (53) have been synthesised by Wittig and Wadsworth-Emmons olefinations of ethyl 2-diazo-4,4,4-trifluoroacetoacetate (52).26 Cyclopentenones (54) have been prepared in a single step by the reaction of 2-alkoxycarbonyl-2-oxopropylidenetriphenyl-phosphoranewith 1,2-dia~ylethenes.~'Similar reactions with 1,2,2-tricarbonylethenes,e.g. (SS), carrying a chiral substituent provided optically active cyclopentenones with high stereoselectivity.

(53)

@=(Et0)2Pf: or Ph,P+ 0

0

0,

TBDMS

(55)

(54) R1 = Ph, Me R2 = Ph, Me or SEt

246

Organophosphorus Chemistry

M e e i - N H 2

+ ROH + Ph3P=CHCN

-

Me

(56) H

H

' be

2.2.3 Miscellaneous Reactions. - p-Toluenesulfonamide undergoes Mitsunobutype reactions in the presence of alcohols and cyanomethylenetriphenyl-phosphorane (56) to give predominantly mono-N-alkylation products.28This reaction has also been applied to the synthesis of cyclic ethers from diols and cyclic amines from amino alcohols29 and to carbon-carbon bond formation.30 Examples of cyclic amine synthesis include that of (+)+skytanthine (57).29 A comparative study of the reactions of active methine compounds (58) as nucleophiles using (56) as a coupling agent, with similar reactions using other Mitsunobu-type coupling agents indicates that while reactions involving (56) require a higher temperature they generally give the highest yields.30 Methoxycarbonylmethylenephosphorane (59) has been reported to act as a methylating agent towards amines, carboxylic acids, phenol and ~hthalimide.~~ The suggested mechanism (Scheme 2) involves initial formation of the Mitsunobu intermediate (60) and ketene.

+ MeOH

[

0

Ph3P+-Q2-$QMe -2Me

]-

MeOP+Ph3OMe-

(60)

+ CH2=C=O

p

H

R2NMe + Ph3P=O

Scheme 2

6: Ylides and Related Compounds

247

Reagents: i, Ph3P=CH2;2 x BuLi, toluene; iii, R'R2C0 Scheme 3

The reaction of methylenetriphenylphosphorane with epichlorohydrin followed by addition of butyllithium and an aldehyde in toluene provides alkylidenecyclobutanols in moderate to good yield (Scheme 3).32 Similar reactions have previously been reported to afford alkylidenecyclo-propylmethanols(6 1) and the current report demonstrates that the reaction is highly base- and solventdependent. Further studies of the kinetics and mechanism of the addition of cyclopentadienylidenetriphenylphosphorane to tetrahalo-p-benzoquinoneshave included the reaction with tetraiodo-p-benzoquinoneto give the 2,s-disubstituted quinone (62).33Initial attack on sulfur is presumably involved in the reaction of two equivalents of stabilised phosphoranes with 5-arylimino-4-chloro-SH-1,2,3dithiazoles (63) to give a mixture of N-arylcyanothioformamides(64)and, as the major product, the novel ylides (65).34 In one example the structure of (65) was confirmed by X-ray crystallography.

Reports of reactions of ylides with carbonyl compounds other than ketones and aldehydes continue to appear. Under extreme conditions lactones (66) undergo Wittig reactions with methoxycarbonylmethylene ylide, generally with

Organophosphorus Chemistry

248

"Po+ *R1YTcHco Ph3P=CHC02Me

R~O

0

~

Toluene 140 "C

R20

3

(67) n=4-9

OR3

(68)

COAr

Br

PhMCH2P+ph3

- i -P h H c Q P P h 3

COAr

(71) Reagents: i, EtsN, toluene, 25 "C, 20 h; ii, xylene, reflux, 24 h

Scheme 4

RCON=C=X

+

Ph3P=CHCN

-

x

CN HNxCOR (75) x - 0 (76) X = S

-

+PPh3

Cr

HCI HX+

NYNH R

(77)

x =0

(78)x = s

6: YIidesand Related Compoundr

249

,CH2R’ Ph2P+\ 0

/

-c-c,I/ - - Li+ NPh

,CHR’

Reagents: i, PhN=C=O; ii, R2R3CO;iii,eHex-N=C=N-eHex

Scheme 5

poor stereo-~ontrol.~~ Medium-ring lactones (67)and reactive ylides in DMSO follow a quite different route to give unsaturated alcohols (68).36A mechanism based on 31PNMR and D20 quenching experiments is proposed for the reaction. Treatment of the 1,2,3-triazol-5-yl-methylphosphonium salts (69)with amine as a base gave the stable ylides (70)v i a internal a~ylation.~’ On refluxing in xylene (70) gave the tricyclic [2,3]benzodiazepines (7 1) while reaction at lower temperatures gave the pyrazoles (72) (Scheme 4).The reactions of carbon suboxide with phosphonium ylides have been extended to ketenylidenetriphenylphosphorane (73)where a double [2+2] cycloaddition gives the spirocyclobutanedione bisylide (74).38The structure of (74) has been confirmed by single crystal X-ray analysis. The adducts (75)and (76)derived from the reaction of cyanomethylenetriphenylphosphorane with, respectively, acylisocyanates and acylisothiocyanates, undergo cyclisation on treatment with HCl to give the pyrimidones (77) and (78).39 Further reactions of these last compounds provide routes to non-phosphoruscontaining pyrimidine derivatives. Continuing their investigations of ylide-anions (79), Cristau’s group has investigated the reactions of (79)with phenylisocyanate and with DCC to give the ylide adducts (80)and (82), respectively. In each case these adducts undergo Wittig reactions with carbonyl compounds to give a$unsaturated amides (81) from (80) and amidines (83) from (82) (Scheme 5).40 A modification of the Hantsch thiazole synthesis involving 2-oxo-3-chloropropylidenetriphenyl-phosphorane(84) has been used to synthesise thiazolyhnethylphos phonium salts (85).41Reactions of the ylides derived from (85) with aldehydes provide a wide range of a$-unsaturated thiazoles with variable, but predominantly (9,stereochemistry in moderate to good yield (Scheme 6).

250

Organophosphorus Chemistry

iii

I

Reagents: i, Toluene, 22 "C; ii, Arnberlyst@ 15 Resin (H+),CH2C12.22 "C; iii, R2CH0, LiHMDS, THF, -78 "C

Scheme 6

A number of new studies of the reactions of ylides with oxidising agents have appeared. Dimethyldioxirane (DMD) has been investigated as an alternative oxidant for the conversion of ylides (86) into tricarbonyl compounds (87).42 DMD is suggested to be the preferred reagent in that it provides higher yields at lower temperatures under neutral conditions and selectivity in the presence of a number of other sensitive functional groups. Ozonides (88) react with stabilised ylides and phosphonate carbanions to give alkenes. However, the reaction rate is now reported to be increased dramatically by the presence of t~iethylamine.~~ The rationale for this is based on the thermal energy and the catalytic effect of the ammonium formate produced by the reaction of the ozonide with amine. The reactions of phosphonium ylides with the nitrating agents N2O4 and ethyl nitrate have been investigated.u The reactions are complex and the products (e.g. Scheme 7) depend on the nature of the ylide and the nitrating agent. The elusive a-nitroalkylphosphonium salts are thought to be intermediates in many cases.

251

6: Ylides and Related CompountiS

2Ph3P=CHR

R

N204

RC=N

+

Ph3+PCH2R NO3-

Ph, COR or C02R

I

Scheme 7

In a continuing investigation of FVP of stabilised phosphonium ylides a series of amino acid-derived ylides (89) have been prepared and pyrolysed to give, e.g. (90).45 In one case (89, R = 'Pr) X-ray analysis has been carried out and this indicates a phosphonium enolate structure (9 1). Similarly alkynoylphosphonium ylides (92) and oxalyldiphosphonium ylides (93) have been subjected to FVP.46 While (92) give moderate yields of the expected unsymmetrical 1,3-diynes, 1,3diynes are only obtained from (93) under exceptionally vigorous conditions and then only in certain cases.

FVP ph3Ar p*r

0

PPh3

* ArC='C-C=CAr

252

Organophosphorus Chemistry

(96)

(97) E = Si, Ge or Sn

Novel vanadium, e.g. (94), and titanium, e.g. (95), complexes of phosphonium ylides have been prepared by the reaction of methylenetriphenylphosphorane with appropriately co-ordinated metal halides.47 A variety of silver complexes (96) of ylides have been isolated from reactions of bis(phosphonio)isophosphindolide salts.48 Ylides can also act as ligands through binding to main group elements although in the cases, e.g. (97), recently reported bonding is via phosphorus rather than carbon.49 The double bond in tricarbonyl(styrene) chromium(0) is sufficiently active to react with phosphonium and sulfoxonium ylides to give complexes of phenylcyclopropanes, e.g. (98).50 ,OMe

3

The Structure and Reactions of Phosphine Oxide Anions

A major review of stereocontrol in organic synthesis using the diphenylphosphoryl group has appeared and includes coverage of Homer olefination and other reactions of phosphine oxide-stabilisedcar bani on^.^' A variety of chemical quenching studies provide no evidence of carbon configurational stability in a-lithiated phosphine oxides derived from racemic examples (99) and (100) and from single enantiomers (101) and (102), even under conditions of internal quenching at -78 "C where the timescale for inversion/ rotation is short.52An even more sensitive probe for configurational stability is the Hoffmann tests3 Application of this test to phosphine oxide-stabilised anions has involved comparison of the diastereomeric ratio of products from the reaction of lithiated ethyldiphenyl-phosphine oxide with the racemic phenylala-

6: Ylides and Related Compoun&

253

nine-derived aldehyde (103) with that ratio obtained from a similar reaction of enantiomerically enriched aldehyde.% This method allows the configurational stability of lithiated primary alkylphosphine oxides, e.g. (104), to be investigated and the results indicate that such compounds are not configurationally stable in THF at temperatures as low as - 78 "C.Rapid racemisation via formation of the anion (106) is the suggested explanation for failure to obtain optically active 2(diphenylphosphinoy1)propanoic acid by hydrolysis of the corresponding, optically pure ester (105).55

X II Ar-"'Me I Me

i

X II Ar CH2Li 4 Me

-

'-

-

X

ii

Me

Reagents: i, RLi. (-)-Sparteine; ii, PhZCO; iii, Cu(0Piv)p Scheme 8

254

Organophosphorus Chemistry

Both dimethylphenylphosphine-borane (107) and -sulfide (108) are enantioselectively deprotonated by a lithiumalkyl ( -)-sparteine complex as demonstrated by subsequent reaction with electrophiles to give products with e.e. values of 8087% (Scheme 8).56 Oxidative coupling of (109) in the presence of copper(I1) pivalate gives the (S,S)-isomer (1 10) as the major product. Asymmetric metallation and silylation of diphenylphosphinyl ferrocene (111) using the chiral lithium amide base derived from di(1-methylbenzy1)aminehas been reported to give an e.e. value of 54% (Scheme 9).57 Attempts at similar reactions of ferrocenes carrying other carbanion-stabilising substituents gave either no reaction or racemic products.

Reagents: i, Ph''

N

Li

Ph, Me3SiCI, THF, -78 "C

Scheme 9

One of the limitations of the Warren's adaptation of Horner-Wittig olefination, the failure of the (2)-selective route when the alkene has a branched chain substituent, has now been overcome.58Reduction of the P-ketophosphonates carrying a-branches, e.g. (1 12) and (1 13), with sodium borohydride and cerium chloride gives excellent anti-stereoselectivity and hence (2)-alkene on baseinduced elimination. Enantioselective synthesis of both syn-( 115) and anti-( 117) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate appro ache^.^^ The syn-isomer was obtained by reduction of the corresponding ketone (1 14), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethylphosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported.60 Cerium(II1) chloride-promoted NaBH4

R2

0

(112) R' = R2 = Me (1 13) R', R2 = (CH2)5

Ph2P=O

R2

OH

6: Ylides and Related Compounds

255

Ph

Ph

Ph

Ph

0

II Reagents: i, NaBH4, CeCI3.7 H20, EtOH, -78 "C; ii, Ph2PCH2Li,THF, -78

"C

Scheme 10

nucleophilic addition of organolithium reagents to u-alkyl-P-ketophosphine oxides, e.g. (1 18), provides P-hydroxyphosphine oxides, e.g. (119), with excellent diastereoselectivity and in excellent yield. Finally, treatment of (1 19) with potassium hydride gives the corresponding alkene stereospecifically. Reaction of y-benzoyloxyphosphine oxides (120) with LDA in the presence of trimethylchlorosilane gives the silylated intramolecular acylation-intermediates (12 1) with a high degree of stereoselectivity.61Treatment of (121) with potassium butoxide provides a route to optically active, substituted cyclopropyl ketones in good yield (Scheme 11). Full details of the regioselective ring-opening of phosphonate-substituted epoxy alcohols (122) with nucleophiles to give Horner-Wittig intermediates (123) have been published.62A variety of allylic alcohols, unsaturated P-hydroxy sulfides, homoallylic alcohols, and unsaturated amino acids have been synthesised with control of absolute (R,S), relative (syn, anti) and geometrical (E,2) stereochemistry. The combination of stereoselective generation of stereogenic centres with stereoselective Horner-Wittig olefination has been extended to provide alkenes with three stereogenic centres of defined ~tereochemistry.~~ The lactones (124) can be alkylated to give (125) with >95% stereoselectivity. Epoxidation, ring-opening with thiophenate, reduction and finally base-treatment gives (126) with good stereocontrol at all chiral centres (Scheme 12).

256

Reagents: i, Me3SiCI; ii, LDA, -78 “C; iii, Bu’OK, BdOH

Scheme 11

Reagents: i. 1.5 x LiHMDS; ii, 10 x RX, 10 x DMPU; iii, 2 x mCPBA, CH&; iv, PhSLi, THF; v, LiBH4,THF; vi, KOH, DMSO, 55 “C

Scheme 12

6: Hides and Related Compounds

257

,CH2CH= CHMe

0 I1

MeCH=CHCH2Bri1*.&!Ph2 R'

Me0

OMe (127)

0

n

0 I1

Ph2P, Lit

"

A21

R3

The regiochemistry of the reaction of lithiated carbanions derived from a-methoxyallylphosphine oxides with a$-unsaturated carbonyl compounds has been investigated.& Transmetallation of the lithium cation with chlorotitanium triisopropoxide gave exclusively 1,4-addition and this approach, followed by quenching with electrophiles, offers a route to a range of synthetically useful phosphonates, e.g. (127), in moderate yield. The anion of allyldiphenylphosphine oxide reacts with epoxides in DME containing BF3-etherateto give a mixture of a-( 128) and p-( 129) a d d ~ c t sCarbanions .~~ derived from P-hydrazonophosphine oxides (130) react regioselectively with isocyanates to give mixtures of the afunctionalised hydrazono- (131) and enehydrazino- (132) derivatives (Scheme 13).66 Similar reactions with isothiocyanates gave the hydrazono derivatives (1 34) as the only products. Treatment of the products (131), (132) and (134) with phosphorus oxychloride and triethylamine provides a synthesis of pyrazoles (133) and (135). Two modes of reaction of N-vinylic phosphazenes with activated carbonyl compounds have been observed.67 The phosphazenes (136) derived from triphenylphosphine undergo y-addition reactions to give adducts (138), while phosphazene (137) derived from diphenylmethylphosphine reacts with ethyl glyoxylate to give (139) via the Staudinger reaction. Cyclopropylphosphine oxides (140) react with the sodium salts of amides, presumably via cyclopropane ring-opening and intramolecular olefination, to give dihydropyrrole derivatives in moderate to good yield.68 Vicarious nucleophilic substitution reactions of a variety of substituted nitrobenzene derivatives with the carbanion of chloromethyldiphenylphosphineoxide to give o-( 141) and p(142)nitrobenzyldiphenylphosphineoxides have been in~estigated.~~ Examples of phosphine oxide carbanions acting as ligands in organometallic compounds include gold and silver complexes, e.g. (143) and (lU).70

Organophosphorus Chemistry

258

Me2N\ M e q N H R 2

-

Me

iv

QNHR2 Me ,,PPh2

Ph2P=O

0'

t 134)

(135)

Reagents: i, LDA; ii, R2NCO;iii, H20; iv, CI3PO, Et3N;v, R2NCS

Scheme 13

00

% R2=Me,R = H

(136) R2=Ph (137) R2=Me

N+CHC02Et

1

6: Ylides and Related Compound

259 "

(140) X = CN or C02Et

yo2

0

Ph3P-M-C-POPh2

\

POPh2

(143) M = A u (144) M = A g

4

The Structure and Reactions of Phospbonate Anions

Phosphonate-stabilisedcarbanions (145) have been generated by the addition of organo-cuprate reagents to vinylphosphonates and then trapped by electrophiles to give a variety of a-substituted alkylpho~phonates.~~ The electrolysis of diisopropyl trichloromethylphosphonate in the presence of alkylating agents provides a general synthesis of diisopropyl 1,l-dichloroalkyl-phosphonates (146).72Several new theoretical studies of phosphonate carbanion structures have been reported. These include a comparative ab initio study of P-C rotational barriers and carbanion stabilisation energies of phosphoryl- and thiophosphorylstabilised car bani on^^^ and an investigation of the various possible isomers of monolithiated methylphosphonic acid using ab initio and PM3-MOmethods.74

0

e-, RX It (P~~O)~PCCI~ * DMF, R.T.

0

II (Pr'O)zPCC12R

Organophosphorus Chemistry

260

Asymmetric and enantioselective olefination reactions continue to be of interest. Wadsworth-Emmons reactions of 4-substituted cyclohexanones with the phosphonate (147), which carries a chiral benzopyrano-isoxazolidinesubstituent, proceed with diastereomeric excesses of 80-90% and hence provide another example of such an approach to enantiomerically pure, axially dissymmetric cyclohexylidene derivative^.^^ A further example of trapping of in situ generated ketenes by Wadsworth-Emmons reactions to give allene carboxylates has been reported76and the reaction has been extended to enantioselectivesynthesis by use of the optically active phosphonates (148) (Scheme 14).77 Moderate to good chemical yields and e.e. values up to 84% were obtained depending on the nature of (148) and the reactions conditions.

R2

H

'

Reagents: i, Bu"Li, ZnCI2, -78

, KHMDS, -78 "C

"C,1h; ii,

,PCH2C02Me

Scheme 14

A one-pot synthesis of 4-hydroxycyclopent-2-en-1 -ones (150), involving (2)stereoselective olefination of a-diketones to give (149) followed by intramolecular aldol condensation, has been reported.78 Wadsworth-Emmons reactions of bis(2,2,2-trifluoroethyl)phosphonosulfoxides (15 1) with aromatic aldehydes give predominantly (Z)-a,P-unsaturated sulfoxides while similar reactions with the corresponding sulfides (152) give or lower (Z)-~electivity.'~In olefinations using (9-dimethyl phosphorylmethyl p-tolyl sulfoxide (1 53) substantial racemisation at sulfur occurs when n-butyllithium is used as base.8O

(a-

4: Ylides and Related Compoundr

261

0 I1

(Me0)2PCH2COCH2R2

R'CoCoR' Ir LiOH.H20/MeOH

[

R:GcH2R2]

R'

(149)

0

o I1

xI I

6;

M e e ! - C H $ ( O M e0 )*

OH

R'

R (o + z ),l,

~2

(CF&H20)2PCH2SR OMe (151) X = O (152) X = lone pair

a-Methoxyallylphosphonates(154), prepared from vinylic acetals, have been used in olefination reactions to synthesise conjugated methoxy dienes with (E)selectivity.81Olefinations to give a mixture of isomers have been achieved by the reaction of carbanions derived from pentaco-ordinated phosphorus compounds (155) with benzaldehyde (Scheme 15).82 A 31PNMR study provides evidence for a number of intermediates and a mechanism is suggested for the reaction on the basis of these. The pentaco-ordinate 1,2-h6-oxathietane(1 56), the sulfur analogue of the presumed intermediate in Wadsworth-Emmons olefination reactions, has been synthesised and its structure determined by X-ray ~rystallography.~~

$7 0. > , P -

CH2C02Me

q0

-2-o-Li+ i, ii

o----p+o

)$7 0

0

(155) Reagents: i, LiHMDS, -78 "C; ii, PhCHO

Scheme 15

+

PhCH=CHC02Me

262

Organophosphorus Chemistry 0

II

(R'0)2PH

i

0 II

(R10)2PCF2H

ii

0 II

(R10)2PCF2R2

(157)

Reagents: i, NaHMDS, CICF2H; ii, LDA, THF, HMPA, R20Tf

Scheme 16

Fluoromethylphosphonates have become increasingly important, to a large extent due to their use as phosphate mimics. Dialkyl lithiodifluoromethylphosphonate has been prepared and reacted with a number of triflates to give substituted phosphonate esters, e.g. (157), which undergo Pd(0) catalysed deprotection to give the corresponding phosphonic acid salts (Scheme 16).84 Ceriummediated reactions of diethyl lithiodifluoromethylphosphonate with esters are reported to provide moderate to good yields of the corresponding a,a-difluoro-Pketophosphonates (158) (Scheme 17).85 A similar reaction with DMF gave the formyl hydrate (159) which undergoes olefination with triethyl phosphonoacetate carbanion. The carbanion derived from diethyl a-fluorobenzylphosphonate (160) also undergoes a-acylation reactions to give the monofluoro derivatives and olefination reactions with aldehydes and ketones to give vinyl fluorides (161), the latter generally with poor stereoselectivity.86 Lithiated dibenzyl a,a-difluoromethylphosphonothioate (162) has been reported to react with a variety of electrophiles in a similar way to the oxygen analogue.87

I

iii

t 0

II

0 II

(Et0)2PCF2CR

Reagents: i, LDA, CeC13, THF, -78 "C; ii, HCONMe2;iii, R C a E t

Scheme 17

6: Ylides and Related Compounds

263

0 It

(Et0)zPCHFPh

+

LDA, R1COR2

-

THF, -78 "C

R1R2C=CFPh

( 160)

S I1 (Bn0)2PCHF2

(161)

LDA

S

I1

(Bn0)2PCF2

I

RX

5

II

(Bn0)2PCF2R

Li (162)

Scheme 18

The use of the carbanion derived from the chloroallylphosphonate(163) in the enantioselective synthesis of cyclopropanes (164)by Michael addition to a$unsaturated ketones has been the subject of a short review (Scheme 18).88 Denmark's group have published full details of the asymmetric Michael addition reactions of cyclic enones with carbanions derived from 1,3,2-oxazaphosphorinane 2-oxides (165) and (167).89 y-Addition to give (166) predominates although the extent of this depends on the ring size of the Michael acceptor. The level of diastereoselectivitydepends on the stereochemistry of the allylphosphonateused; 0

R'

0

0

II

R'

0

K.

264

Organophosphorus Chemistry

the carbanion derived from the cis-diastereomer (165) provides good to excellent selectivity while that derived from the trans-diastereomer (167) gives virtually no selectivity. Similar reactions of the carbanions derived from allylphosphonates (168) carrying a G-symmetric binaphthyl group give excellent diastereoselectivity.gOIn an excellent publication a full account has appeared of the alkylation of the carbanions derived from chiral 2-0~0-1,3,2-oxazaphosphorinanes (169) and 2-thioxo-1,3,2-0xazaphosphorinanes (170).91 In most cases excellent diastereoselectivity was obtained and the results are discussed in terms of the aggregation states and relative conformations of the carbanions involved. X

(169) X = 0, R = Ph, Me or OMe (170) X = S, R = Ph, Me or OMe

The stereoselectivity of [2,3]-Wittig rearrangements of phosphonate carbanions has been studied using compounds with a chiral phosphorus atom and compounds carrying chiral substituents on phosphorus. An example of the former case is the phosphonate (171) which gives (172) with excellent diastereo- and enantio-~electivity~~ while dimenthyl allyloxyphosphonates, e.g. (173), give diastereoselectivitiesof up to 90% (Scheme 19).93The lithiated carbanions derived from the quaternary ammonium substituted phosphonates (174) undergo sigmatropic [2,3]-Wittig rearrangement to give the a-substituted phosphonates (175).% The corresponding amines, unlike the ether and thiol derivatives, do not undergo similar rearrangements.

THF, -78

But

"C

Me

But

OH

(172) > 99% e.e.

Reagents: i, 5 x BuLi, THF, -78"C,3 h; ii, 4MHCI

Scheme 19

6: Ylides and Related Compounds

265 0

DMF,

4 0 "C, 1.5 h

R3

2-Phosphono-substituted dienes (177) have been prepared by the reaction of diethyl a-trimethylsilylprenylphosphonatecarbanion with alkyl formates to give the acylation intermediate (1 76) which undergoes spontaneous Peterson elimination (Scheme 2O).'' The reaction of 2,2,2-trifluoroethyl trifluoroacetate with lithiated dimethyl methylphosphonate has been used in a new, more convenient synthesis of dimethyl diazomethylphosphonate(178) (Scheme 21).96The method has the added attraction that acid conditions can be avoided throughout. Treatment of the (dihydrofurany1)phosphonates (180), obtained by iodocyclisation of (179),with potassium tertiarybutoxide provides a synthesis of P-(diethoxyphosphiny1)-cqp-unsaturated ketones (182) presumably by rearrangement of the carbanion (181) (Scheme 22).97

OH

Reagents: i, LDA, THF. -70 "C; ii, Me&iCI, -70 "C; iii, 2 x HC02R,-70 "C; iv, H3O' Scheme 20

Organophosphorus Chemistry

266

Reagents: i, BuLi, THF, -78 "C; ii, CF3C02CH2CF3, THF, -78

"C

iii, M e C O N Ho S 0 2 N 3 , MeCN. EtsN, 0 "C

Scheme 21

Reagents: i, BuLi, THF, -78 "C; ii, R3COR4; iii, 12, H20, NaHC03; iv, BubK

Scheme 22

0

+ (Et0)2PCH2Li II

F3C >CH2 Ph

0

-%%

(EtOhg+F

Ph

6: Ylides and Related Compoundr

267

The gem-difluoroalkenylphosphonate(183) has been synthesised by reaction of 1-Substilithiated diethyl methylphosphonate with a-trifluor~methylstyrene.~~ tuted 5-trifluoromethylimidazole-4-phosphonates(185) have been prepared in moderate yield by the reaction of isocyanomethylphosphonate carbanions with trifluoroacetimidoyl chlorides (184).99 Diphosphono-alkylation of nucleophiles has been achieved in one pot by sequential treatment of phosphonate carbanions with alkyl dichlorophosphates and the conjugate acid of the appropriate nucleophile (Scheme 23). loo

1

-

0 II i, ii (R’O~)PCH~R*

1

0 0 II II (R’O~)PCHP-CI

L

k2bR3

-

0 II

Li 0 I

II

(R’02)P-C-P-CI

A2 AR3

J

I

iii, iv

0 0 I1 II (R’O~)P-CH-P-NIJ

A2

&R3

0 I1

Reagents: i, BuLi, THF, -78 “C, 0.5h; ii, CI2POR3;iii, NuH; iv, H20

Scheme 23

5

Selected Applications in Synthesis

A series of review articles on the synthesis of biofunctional molecules have appeared and several of these describe extensive use of phosphorus-based olefination reactions, for example, in the synthesis of vitamin D, tetramic acids, polyene macrolide antibiotics and bioactive marine macrolides.lol

5.1 Amino Acids and Peptides. - Wasserman’s method of one-carbon homologation of carboxylic acids to give u-ketocarboxylates involves reaction with cyanomethylenetriphenyl-phosphoranefollowed by ozone (Scheme 24) and has been used as a key step in a chemo-enzymatic synthesis of isotopically labelled L-valine, L-isoleucine, and ah-isoleucine. lo2 Alkylation of the carbanion derived from the imino-substituted methylphosphonate diphenyl ester (186) with indol-3-ylmethyl bromide followed by appropriate deprotection has been used to prepare the phosphonate analogue (1 87) of tryptophan (Scheme 25).lo3 The deprotected analogue (188) and derived peptides show activity as inhibitors of chymotrypsin. Two approaches to solid phase Wadsworth-Emmons reactions which have applications in combinatorial chemistry have been reported.lo4 In one diethylphosphonoacetamideis bound to PEG-PAL resin via a peptide link, while

268

Organophosphorus Chemistry

-

+$H3

R'YCo2H R2

R'

C02Me-

R2

R2 Ph3P

R2

Reagents: i, Ph3P=CHCN, DMAP; ii,03, MeOH, CH2CI2: iii, Candida cylindracea leucine dehydrogenase, NADH, FDH, HCO$H~

Scheme 24 0

(187) R - BOC (188) R = H

CH2Br ; iii, TFA, CH2Cl2

THF, -78 "C; ii. Reagents: i, KN(T~v~S)~,

Scheme 25 0

0

N /II/F(OEt)2

0 i

Hb N

~

H

N H

N-NB~~ H

H

NHCbz

Reagent: i, RCHO, LiBr, Et3N

Scheme 26

R

+

t

(Et0)zPOH

6: Ylides and Related Compounds

269

in the other the link is to Tentage1 threonine via a phosphonate ester (Scheme 26). In the latter case the olefination reaction also releases the alkene product from the resin. In both cases mild, peptide-compatible base systems are used. The C(9)C(37) fragment (190) of calyculin A, a natural protein phosphatase 1 and 2A inhibitor, has been constructed by a Wittig reaction of the complex phosphonium salt (189).lo5Since (190) has previously been converted to calyculin A this report constitutes a formal total synthesis of the latter compound. The Wittig reaction has been used to introduce the double bond in a synthesis, and hence to determine the absolute configuration, of the immunosuppressant mycestericin E (191).lo6However, the olefination step is claimed to give 89% (E)- alkene in spite of being drawn as (2); the latter is the stereochemistry required in later steps.

Me2N

6Bu3 B r

OTES

Me

JuMe

Me

OMe O x 0

5.2 Carbohydrates. - The phosphonic acid (193), an analogue of the bacterial cell wall component 3-deoxy-D-manno-2-octulosonic acid, has been synthesised by the reaction of 2,3:5,6-di-O-isopropylidene-D-mannitol triflate with the formylphosphonate anion equivalent (192) followed by depr~tection.’~’ Compound (1 93) slowly decomposed to give the corresponding lactone and

270

Organophosphorus Chemistry

phosphonous acid even at - 15 "C.The phosphonate isostere (196) of 2deoxyribose-3-phosphate has been prepared using the reaction of diethyl methylphosphonate carbanion with epoxide (194) as the key step.lo8Reaction of the phosphonate carbanion with the triflate (195) led to elimination rather than the required substitution.

0 II

0 I1

+ fEt0)2PCH2Li

&R1

BnO

(1 94)

-

BnOZ

R, Y OH

)

'

6: Ylides and Related Compoundr 0 (W2P IIL

271

S02Me

\O (200)

R

+

-CHo \BuLi,

THF, -78 "C-RT q u l f o ny lation

1 OR (201) R = AC

5.3 Carotenoids, Retenoids, Pheromones and Polyenes. - (All-E)-(3S,5R,6R)Paracentrone (199), first isolated from the sea urchin Paracentrotus Zividus, has been synthesised using Wittig reactions of ylides (197) and (198) as key steps.log The Wittig reaction continues to be used in the synthesis of retinals, for example, side-chain methyl-shifted analogues,Il0 but little or no new chemistry has been reported. (&Selective Wadsworth-Emmons olefination using the Qsulfonylalkylphosphonate (200) followed by stereospecific desulfonylation has been used to synthesise the sex pheromone (201) of the potato tuberworm moth Phthorimaea operculella. (32, 6E)-a-Farnesene (204) has been prepared by Horner olefination of methyl vinyl ketone with the phosphine oxide (202) (Scheme 27).l12 The nature of the base used has a large effect on the yield and the authors report that it is more efficient to carry out the elimination step directly with the mixture of diastereo-

\iii

Reagents: i, LDA; ii, MeCOCH=CH2; iii, NaH, THF

Scheme 27

272

Organophosphorus Chemistry

mers (203) and separate the required isomer (204) at the end of the reaction. (15E)-(207)- and (1 52)-(208)- ( 2 )-16-oxa-2,3-oxidosqualenes,potential inhibitors of oxidosqualene cyclase, have been synthesis4 using the Horner reaction of the phosphonate (205) and the epoxyaldehyde (2O6).ll3 Further use of phosphorus-based olefination in the asymmetric total synthesis of the antimitotic agent curacin A (211) has been reported,l14 the phosphonate (209) and the salt (210)being involved in key steps.

The monomers (213), which were ultimately converted into novel conjugated polymers, have been prepared in poor yield by double Wittig reaction of the dialdehyde (212).lI5 Bis-Wittig reactions of 1,3-propanebis(triphenylphosphorane) (214)with ferrocenyl aldehydes (215 ) have been used to prepare a series of bis(ferroceny1)polyenes(216) containing a central methylene group.' l6 These compounds were converted into the corresponding polymethine cations which are prototype molecular wires with redox-active end groups.

6: Ylides and Related Compounds

213

OHCAcHo

Fe

+

PhsP=CHCH2CH=PPh3

-

Fe

I

(215) n = 5,9or 13

5.4 Leukotrienes, Prostaglandins and Related Compounds. - Phosphorus-based olefination, particularly the Wittig reaction, continues to be widely used as a synthetic method in this area although the overall level of activity is reduced this year. 19(R,S)-Fluoroleukotriene & methyl ester (217) has been synthesised via Wittig coupling of 8-(fluoro)non-3-enyltriphenylphosphorane. A Wittig reaction of the ylide (220) with a mixture of monoacetal (218) and diacetal (219) gives exclusively (2)-triene (221) and this has been used as a key step in the synthesis of (all-Z)-5,8,11,14,17-eicosapentaenoic and -4,7,10,13,16,19docosahexaenoic acids. l 8 lo-($)-( -)-Hydroxy-eicosa-5-(2),8-(2), 11-(a, 14-(2)tetraenoic acid (222) has been synthesised from (R)-glyceraldehyde acetonide using (2)-selective Wittig reactions of the salts (223) and (224) as key steps.11g

274

Organophosphorus Chemistry

5.5 Macrolides and Related Compounds. - Complex phosphonates continue to be used in the construction of carbon skeletons and in cyclisation reactions, as exemplified by the synthesis of didesepoxyrhizoxin, the biogenetic precursor of the antitumour agent rhizoxin, via intramolecular olefination of (225). 12* (+)Trienomycins A and F, members of a family of ansamycin antibiotics, have been synthesised using a double Wittig reaction of the diphosphonium salt (226) as a key step.I2*The reaction produces a mixture of isomers including 21% of the required (all-E)product.

I

OMe

6: Ylides and Related Compounds

275

OR2

5.6 Nitrogen and Oxygen Heterocycles. - There continues to be a large number of reports of the use of the reactions of iminophosphoranes, primarily the azaWittig reaction, to synthesise a wide range of heterocyclic systems although much of this is routine in terns of phosphorus chemistry. Examples of this type of approach include the reaction of the pyrazine derivative (227) with isocyanates to give, in one example, pteridin-4(3H)-ones (228)122and intramolecular aza-Wittig 0

PhCH20 ““O&--

N-

Organophosphorus Chemistry

216

reactions of iminophosphoranes derived from azides (229) to give 1,4benzodiazepin-5-onederivatives (230).123This latter reaction has been applied to the synthesis of the 0-benzyl derivative (231) of the anti-tumour antibiotic DC81. Further use of vinyliminophosphoranes in synthesis has been reported.124 Reactions with a,&unsaturated aldehydes lead to mixtures of 2-substituted pyridines (232) and dihydropyridines (233) while reactions with aromatic aldehydes give exclusively dihydropyridines. R

5,8-Dimethoxy-2(1H)-quinolines (235), which are key intermediates for the synthesis of antimalarial drugs, have been prepared in poor to moderate yields by intramolecular Wittig reaction of the salts (234).125A combination of Wittig olefination and Claisen rearrangement of (2-hydroxy-4-preny1oxy)phenyl carbony1 compounds (236) has been used in a one-pot synthesis of 2’,3’,3‘-trimethyl2’,3’-dihydroangelicins(237).’26 OMe R’

WPh3 Br

Et3N

____t

OMe

6: Ylides and Related Compounds

277

(238)@

= Bu,P+

@ = (Me0)2PO

(239)

d’

5.7 Tetrathiafulvalene Derivatives and Related Compounds. - Olefination reactions of both phosphonium salts (238) and phosphonates (239) continue to be used in the synthesis of conjugated 1,3-dithiole structures, e.g. (240)127and the selenium analogue (241). 12* The analogous 1,3-diselenolephosphonium salt (242) has been synthesised by a new, more efficient route and used in Wittig reactions with a variety of aldehydes to give the corresponding 2-ylidene-l,3diselenones.129 The reaction of 2,3-dichlorobenzoquinoneswith the carbanion of the phosphonate (243) gives the novel 1,4-dithiin-fused quinones (244) rather than the expected n-extended p-quinomethane analogues.130 No explanation for this reaction, in which a carbon atom is lost, is offered. However, a similar reaction with 2-chloro-1,4-naphthoquinone also gave the corresponding 1,4dithiin derivative.

Both Wittig and Wadsworth-Emmons reactions have been used to synthesise functionalised oligo(viny1thiophenes)(245) for use as potential liquid crystal and non-linear optical materials.*31

278

Organophosphorus Chemistry

(245) n = 1 o r 2

5.8 Miscellaneous Reactions. - A wide range of often very complex phosphonium salts, phosphonates and phosphine oxides have been used in synthesis (see also section 5.5). These include intramolecular olefination of the phosphonate (246) to construct ring A in a total synthesis of brevitoxin B13*and a similar reaction of the phosphonate (247) as the key step in the synthesis of cephalostatin.133 Wittig reactions of complex phosphonium salts, e.g. (248), have been used to construct the total carbon skeleton in the synthesis of annonaceous acetogenins, a family of compounds with a wide range of biological activity.134 Fluorinated, lipophilic A-ring analogues of 1,25-dihydroxy vitamin D3 have been prepared using standard Horner olefination reactions of (249).13'

i2H

H

CO2Et

o x PO(OEt)2

RO&O ' M.

(247)

Me

'0611

6: Ylides and Related Compounds

279

(CH2)ltCONH2 OHCS'

(252) m = 14 (253) m = 15

(CH21120MOM

A Wadsworth-Emmons reaction of the phosphonate (250) with the aldehyde (251) has been used as a key step in a total synthesis of analogues (252) and (253) of topostin B-1, an inhibitor of mammalian DNA topoisomerase I.136 The enzyme-catalysed aldol condensation between the phosphonate aldehyde (254) and dihydroxyacetone phosphate is followed by spontaneous intramolecular olefination of the product to give the cyclitol (256) in spite of the reaction being below pH 7 at all times.13' Attempts at a similar reaction of the homologue (255) were unsuccessful probably because (255) is a poor substrate for the aldolase.

(254)

f/ =

1

(255)n = 2

bcH; 0

2.2 x Ph3P=CH(CH2)3C-0°It

OHC

\

Organophosphorus Chemistry

280

0

II

(EtO)2pMe

0 II

(Et0)2PCH2TePh

iii ii

0

II -

(Et0)2PC(TePh)2

iv‘=(reph R

TePh

(260) Reagents: i, LDA; ii, PhTeBr; iii, 3 x LDA; iv, R’RCO

(2611

Scheme 28

Following the failure of other approaches 1,3-di(5-carboxypent-1-yl)benzene derivatives (257) have been prepared by double Wittig reactions on the appropriate 1,3-diformylbenzene derivative.13* Wittig reactions of the phosphonium salt (258) under phase transfer conditions have been used to prepare a variety of compounds (259) with extended conjugation.139 Ketene phenyltelluroacetals (26 1) have been synthesised by a WadsworthEmmons reaction of the di(phenyltel1urium)methylphosphonate carbanion (260) (Scheme 28).I4O

References 1. 2. 3. 4.

5. 6. 7. 8. 9. 10. 11.

12. 13.

‘The Chemistry of Organophosphorus Compounds’, Volume 3 (Phosphonium Salts, Ylides and Phosphoranes), F.R. Hartley (Ed.), Wiley Interscience, Chichester, 1994. X-M.Zhang, A. J. Fry, and F. G. Bordwell, J. Org. Chem., 1996,61,4101. M . Seki and K. Matsumoto, Synthesis, 1996, 580. D. V. Griffiths, P. A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. Research (S), 1996, 176; D. V. Griffiths, P. A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. SOC.,Perkin Trans. I , 1996, 555. G. E. Lathourakis and K. E. Litinas, J. Chem. SOC.,Perkin Trans. I , 1996,491. J. Barluenga, M. Tomas, K. Bieger, S. Garcia-Granda, and R. Santiago-Garcia, Angew. Chem. In?. Ed Engl., 1996,35,896. P. Dyer, 0. Guerret, F. Dahan, A. Baceiredo, and G. Bertrand, J. Chem. Soc., Chem. Commun., 1995,2339. H. H. Karsch, T. Rupprich, and M. Heckel, Chem. Ber., 1995,128,959. U. Heim, H. Pritzkow, U. Fleischer, H. Grutnnacher, M. Sanchez, R. Rkau, and G. Bertrand, Chem. Eur. J., 1996,2,68. A. Schmidpeter, G. Jochem, and H. Noth, Chem. Eur. J., 1996,2,221. H. J. Bestmann, H. P. Oechsner, L. Kisielowski, C. Egerer-Sieber, and F. Hampel, Angew. Chem. In?. Ed. Engl., 1995,34,2017. H-P. Schrodel, G. Jochem, A. Schmidpeter, and H. Noth, Angew. Chem. Int. Ed. Engl., 1995,34, 1853. M. J. P. Harger and B. T. Hurman, J. Chem. SOC.,Chem. Commun., 1995,1701.

6: Ylides and Related Compoun&

28 1

14.

B. Kramer, E. Niecke, M. Nieger, and R. W. Reed, J. Chem. SOC.,Chem. Commun.,

15.

G. Jochem, K. Karaghiosoff, S. Plank, S. Dick, and A. Schmidpeter, Chem. Ber.,

16. 17. 18. 19. 20.

G. Jochem, A. Schmidpeter, F. Kulzer, and S . Dick, Chem. Ber., 1995,12$, 1015. E. Niecke, P. Becker, M. Nieger, D. Stalke, and W. W. Schoeller,Angew. Chem. Int. Ed. Engl., 1995,34, 1849. A. Miiller, B. Neumiiller, and K. Dehnicke, Chem. Ber., 1996,129,253. H. Yamataka, T. Takatsuka, and T. Hanafusa, J. Org. Chem., 1996,61,722. S . Walker, C. Laurent, C. Sarter, C. Puke, and G. Erker, J. Am. Chem. Soc., 1995,

21.

T. Kawashima, T. Soda, and R. Okazaki, Angew. Chem. Int. Ed. Engl., 1996, 35,

22. 23. 24. 25. 26. 27.

V.J. Patil and U. Mavers, Tetrahedron Letters, 1996,37, 1281.

28.

T. Tsunoda, H. Yamamoto, K. Goda, and S . It6, Tetrahedron Letters, 1996, 37,

29.

T. Tsunoda, F. Ozaki, N. Shirakata, Y. Tamaoka, H. Yamamoto, and S . It6, Tetrahedron Letters, 1996,37,2463. T. Tsunoda, C. Nagino, M. Oguri, and S . It6, TetrahedronLetters, 1996,37,2459. D. DesmaSle, Tetrahedron Letters, 1996,37, 1233. Y. Tanaka, G.Koda, and H. Ohta, Tetrahedron Letters, 1995,36, 5591. M. Pons, F. P. Pla, R. Valero, and C. D. Hall, J. Chem. SOC.,Perkin Trans. 2., 1996,

1996, 513. 1995,128,1207.

117,7293. 1096.

G. Bellucci, C. Chiappe, and G. L. Moro, TetrahedronLetters, 1996,37,4225. C. Subramanyam, Tetrahedron Letters, 1995,36,9249. U. Klar and P. Deicke, Tetrahedron Letters, 1996,37,4141. M. Guillaume, Z. Janousek, and H. G. Viehe, Synthesis, 1995,920, M. Hatanaka, A. Ishida, Y.Tanaka, and I. Ueda, Tetrahedron Letters, 1996, 37, 401. 2457.

30. 31. 32. 33.

1011. 34. 35. 36. 37. 38. 39.

40. 41.

H-S. Lee and K. Kim, Tetrahedron Letters, 1996,37,869. M. Lakhrissi and Y. Chapleur, Angew. Chem. Int. Ed Engl., 1996,35,750. Y. Brunel and G. Rousseau, Tetrahedron Letters, 1996,37,3853. E. Laskos, P. S. Lianis, N. A. Rodios, A. Terzis, and C. P. Raptopoulou, Tetrahedron Letters, 1995,36, 5637. L. Pandolfo, G. Facchin, R. Bertani, P. Ganis, and G. Valle, Angew. Chem. Int. Ed. Engl., 1996,35,83. L. V. Meervelt, 0. B. Smolii, N. I. Mishchenko, D. B. Shakhnin, E. A. Romanenko, and B. S . Drach, Tetrahedron, 1996,52,8835. H. J. Cristau, M. Taillefer, J. P. Urbani, and A. Fruchier, Tetrahedron, 1996, 52, 2005. D. R. Williams, D. A. Brooks, J. L. Moore, and A. 0. Stewart, Tetrahedron Letters, 1996,37,983.

42. 43. 44. 45.

H. H. Wasserman, C. M. Baldino, and S. J. Coats, J. Org. Chem., 1995,60,8231. Y-S. Hon and L.Lu, Tetrahedron, 1995,51,7937. H. J. Bestmann, W. Kamberger, T. Rbder, and R. Zimmermann, Liebigs Ann. Chem., 1996,845. R. A. Aitken, H.R. Cooper, and A. P. Mehrotra, J. Chem. SOC.,Perkin Trans. I , 1996,475.

46. 47.

R. A. Aitken, H. Hirion, C. E. R. Horsburgh, N. Karodia, and S. Seth, J. Chem. Soc., Perkin Trans. 1,1996,485. P. Berno, S. Gambarotta, S. Kotila, and G. Erker, J. Chem. Soc., Chem. Commun., 1996,779.

48. 49.

D. Gudat, M. Schrott, V. Bajorat, M. Nieger, S. Kotila, R. Fleischer, and D. Stalke, Chem.Ber., 1996,129,337. H. H. Karsch, B. Deubelly, U. Keller, 0. Steigelmann, J. Lachmann, and G . Miiller, Chem. Ber., 1996,129,671.

282

Organophosphorus Chemistry

50.

S. E. Gibson, G. R. Jefferson, and F. Prechtl, J. Chem. Soc., Chem. Commun., 1995,

51. 52. 53.

J. Clayden and S. Warren, Angew. Chem. In?.Ed. Engl., 1996,35,241. P. O’Brien and S. Warren, Tetrahedron Letters, 1995,36,8473. R . W. Hoffmann, M. Julius, F.Chemla, T. Ruhland, and G. Frenzen, Tetrahedron,

54. 55.

P. O’Brien and S. Warren, Tetrahedron Letters, 1996,37,4271. D. J. Cross, L. J. Farrugia, P. D. Newman, R. D. Peacock, and D. Sterling, J. Chem. Research ( S ) , 1996,222. A. R. Muci, K. R. Campos, and D. A. Evans, J. Am. Chem. SOC.,1995,117,9075. D. A. Price and N. S. Simpkins, Tetrahedron Letters, 1995,36,6135. G. Hutton, T. Jolliff, H. Mitchell, and S . Warren, Tetrahedron Letters, 1995, 36,

1535.

1994,50,6049.

56. 57. 58.

7905.

61. 62.

P. O’Brien and S. Warren, Tetrahedron Letters, 1996,37,3051. G. Bartoli, E. Marcantoni, L. Sambri, and M. Tamburini, Angew. Chem. Int. Ed. Engl., 1995,34,2046. A. Nelson and S. Warren, Tetrahedron Letters, 1996,37, 1501. J. Clayden, A. B. McElroy, and S. Warren, J. Chem. Soc., Perkin Trans. I , 1995,

63. 64. 65. 66. 67. 68. 69.

H. J. Mitchell and S. Warren, Tetrahedron Letters, 1996,37,2105. E. F. Birse, M. D. Ironside, and A. W. Murray, Tetrahedron Letters, 1995,36,6309. J-K. Ergiiden and E. Schaumann, Synthesis, 1996,707. F. Palacios, D. Aparicio, and J. M. de 10s Santos, Tetrahedron, 1996,52,4123. F. Palacios, D. Aparicio, and J. M. de 10s Santos, Tetrahedron, 1996,52,4857. R-Y. Zhang and C-G. Zhao, J. Chem. SOC., Chem. Commun., 1996,511. N. J. Lawrence, J. Liddle, and D. A. Jackson, Tetrahedron Letters, 1995, 36,

59. 60.

1913.

8477. 70.

M. C. Gimeno, P. G. Jones, A. Laguna, and M. D. Villacampa, Chem. Ber., 1996,

71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81.

I. C. Baldwin, R. P. Beckett, and J. M. J. Williams, Synthesis, 1996,34. P. Jubault, C. Feasson, and N. Collignon, Tetrahedron Letters, 1995,36,7073. M. Kranz and S. E. Denmark, J. Org. Chem., 1995,60,5867. R. Koch and E. Anders, J. Org. Chem., 1995,60,5861. A. Abiko and S. Masamune, Tetrahedron Letters, 1996,37, 1077. K. Tanaka, K. Otsubo, and K. Fuji, Tetrahedron Letters, 1995,36,9513. K. Tanaka, K. Otsubo, and K. Fuji, Tetrahedron Letters, 1996,37, 3735. F. Bonadies, A. Scettri, and C. D. Campli, Tetrahedron Letters, 1996,37, 1899. K . Kokin, S. Tsuboi, J. Motoyoshiya, and S. Hayashi, Synthesis, 1996,637. C. Cardellicchio,A. Iacuone, and F. Naso, Tetrahedron Letters, 1995,36,6563. K. Fettes, L. McQuire, and A. W. Murray, J. Chem. SOC.,Perkin Trans. I , 1995,

129, 585.

2123. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93.

M. L. Bojin, S. Barkallah, and S. A. Evans, Jr., J. Am. Chem. SOC.,1996,118, 1549. F. Ohno, T. Kawashima, and R. Okazaki, J. Am. Chem. SOC.,1996,118,697. D. B. Berkowitz and D. G. Sloss, J. Org. Chem., 1995,60,7047. T. P. Lequeux and J. M. Percy, J. Chem. SOC., Chem. Commun., 1995,2111. H-J. Tsai, Tetrahedron Letters, 1996,37, 629. S . R. Piettre and P. Raboisson, Tetrahedron Letters, 1996,37,2229. H.-U. Reissig, Angew. Chem. Int. Ed. Engl., 1996,35,971. S. E. Denmark and J-H. Kim, J. Org. Chem., 1995,60,7535. K. Tanaka, Y.Ohta, and K. Fuji, J. Org. Chem., 1995,60,8036. S . E . Denmark and C-T. Chen, J. Am. Chem. SOC.,1995,117,11879. S . E. Denmark and P. C. Miller, Tetrahedron Letters, 1995,36,6631. M. Gulea-Purcarescu, E. About-Jaudet, and N. Collignon, Tetrahedron Letters,

94.

M. Gulea-Purcarescu, E. About-Jaudet, N. Collignon, M. Saquet, and S . Masson, Tetrahedron, 1996,52,2075.

1995,36,6635.

6: Ylides and Related Compoun& 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132.

283

H. Al-Badri, E. About-Jaudet, and N. Collignon, TetrahedronLetters, 1996,37,2951. D. G. Brown, E. J. Velthuisen, J. R. Commerford, R. G. Brisbois, and T. R. Hoyl, J. Org. Chem., 1996,61,2540. C-W. Lee, J. E. Hong, and D. Y. Oh, J. Org. Chem., 1995,60,7027. J-P. BCgut, D. Bonnet-Delpon, and M. H. Rock, Tetrahedron Letters, 1995, 36, 5003. W. Huang and C. Yuan, Synthesis, 1996,511. C. Grison, P. Coutrot, S. Joliez, and L. Balas, Synthesis, 1996,731. Chem. Rev., 1995,95, 1695-2260. N. M. Kelly, R.G. Reid, C. L. Willis, and P. L. Winton, Tetrahedron Letters, 1996, 37, 1517. C. Bergin, R. Hamilton, B. Walker, and B. J. Walker, J. Chem. SOC.,Chem. Commun., 1996,1155. C. R. Johnston and B. Zhang, Tetrahedron Letters, 1995,36,9253. F. Yokokawa, Y. Hamada, and T. Shioiri, J. Chem. SOC.,Chem. Commun., 1996, 871. T. Fujita, N. Hamamichi, T. Matsuzaki, Y. Kitao, M. Kiuchi, M. Node, and R. Hirose, Tetrahedron Letters, 1995,36,8599. P. Coutrot, C. Grison, and M. Lecouvey, Tetrahedron Letters, 1996,37, 1595. P. V. P. Pragnacharyulu and E. Abushanab, Tetrahedron Letters, 1995,36,5507. J. A. Haugan, Tetrahedron Letters, 1996,37,3887. A-R. de Lera, B. Iglesias, J. Rodrguez, R. Alvarez, S . Lbpez, X.Villanueva, and E. Padrbs, J. Am. Chem. SOC.,1995,117,8220. T. H. Kim and K. M. Park, Tetrahedron Letters, 1995,36,4833. P. Ramaiah, J. J. Pegram, and J. G. Millar, J. Org. Chem., 1995,60, 6211. J. Park, C. Min, H. Williams, and A. J. Scott, Tetrahedron Letters, 1995,36, 5719. T. Onoda, R. Shirai, Y. Koiso, and S. Iwasaki, Tetrahedron Letters, 1996,37,4397. G. A. Power, P.Hodge, and N. B. McKeown, J. Chem. SOC.,Chem. C o m u n . , 1996, 655. L. M. Tolbert, Z. Zhao, Y. Ding, and L. A. Bottomley, J. Am. Chem. SOC.,1995, 117,12891. T. Durand, J. P. Girard, J. C. Rossi, I. Serkov, D. Kuklev, and V. Bezuglov, TetrahedronLetters, 1995,36,6437. J. Sandri and J. Viala, J. Org. Chem., 1995,60,6627. S . N. Yeola, S. A. Saleh, A. R. Brash, C. Prakash, D. F. Taber, and I. A. Blair, J. Org. Chem., 1996,61,838. A. S . Kende, B. E. Blass, and J. R. Henry, Tetrahedron Letters, 1995,36,4741. A. B. Smith, 111, J. Barbosa, W. Wong, and J. L. Wood, J. Am. Chem. SOC.,1995, 117,10777. T. Okawa, S. Eguchi, and A. Kakehi, J. Chem. SOC.,Perkin Trans. I , 1996,247. S . Eguchi, K. Yamashita, Y. Matsushita, and A. Kakehi, J. Org. Chem., 1995,60, 4006. P. Molina, A. Pastor, and M. J. Vilaplana, Tetrahedron Letters, 1995,36,8283. P. Ferrer, C. Avendaiio, and M. Sollhuber, Liebigs Ann. Chem., 1995,1895. R.S . Mali and P. K. Sandhu, J. Chem. Research ( S ) , 1996,148. A. Ohta and Y. Yamashita, J. Chem. SOC.,Chem. Commun., 1995,1761. Y. Misaki, H. Fujiwara, T.Yamabe, T. Mori, H. Mori, and S . Tanaka, J. Chem. SOC.,Chem. Commun., 1996,363. A. Chesney, M. R. Bryce, M. A. Chalton, A. S. Batsanor, J. A. K. Howard, J-M. Fabre, L. Binet, and S. Chakroune, J. Org. Chem., 1996,61,2877. N. Martin, L. Shnchez, C. Seoane, J. Gam, and J. Orduna, Tetrahedron Letters, 1995,36,7153. C. Maertens, J-X. Zhang, P..Dubois, and R. JCrGme, J. Chem. SOC.,Perkin Trans. 2, 1996,713. K. C. Nicolaou, F. P. J. T. Rutjes, E. A. Theodorakis, J. Tiebes, M. Sato, and E. Untersteller, J. Am. Chem. SOC.,1995,117, 10252.

Organophosphorus Chemistry

284 133. 134.

S. Bhandaru and P. L. Fuchs, Tetrahedron Letters, 1995,36,8347.

S . C. Sinha, A. Sinha-Bagchi,A. Yazbak, and E. Keinan, Tetrahedron Letters, 1995, 36,9257.

135. 136. 137. 138. 139. 140.

G . H. Posner, C-G. Cho, T. E.N. Anjeh, N. Johnson, R. L. Horst, T. Kobayashi, T. Okano, and N. Tsugawa, . I Org. Chem., 1995,60,4617. H. Noguchi, T. Aoyama, and T. Shioiri, Tetrahedron, 1995,51, 10531; ibid, 10545. H. J. M. Gijsen and C-H. Wong, TetrahedronLetters, 1995,36,7057. C. Provent, P. Chautemps, G. Gellon, and J. L. Pierre, Tetrahedron Letters, 1996, 37, 1393. S. K. Thakut and B. D. Hosangadi, Tetrahedron, 1996,52,8755. C. C. Silveira, G. Perin, and A. L. Braga, Tetrahedron Letters, 1995,36,7361.

7 Phosphazenes BY C.W. ALLEN

1

Introduction

This chapter covers the literature of phospha(V)azenes with discussion of lower valent species being restricted to molecules which can be transformed, or related to a phosphorus(V) derivative. Primary literature, reviews monographs and patents are covered in order to give a global view of progress in this area of chemistry. Full manuscripts' and poster abstracts2 from the Thirteenth International Symposium on Phosphorus Chemistry (Jerusalem, 1995) have been published. Highly focused reviews will be cited in the appropriate sections below. 2

Acyclic Phosphazenes

The chemistry of acyclic phosphazenes (iminophosphorane, phosphoranimines) continues to be a fertile area at the intersection of organic and inorganic chemistry. The role of charge effects on phosphorus-nitrogen (PN) bond lengths has been studied by structural comparisons of Ph3PNMeBH3 and Ph3PNMe2+BF4-.3 A wide range of acyclic phosphazene structures have been reported and are collected in section 7.Indirect detection of 15NNMR parameters from 31P correlation experiments have been reported for phosphazenes e.g. R(Ph)2P=NR and Ar(Me)C=NPPh2=NCOPh. One dimensional experiments give 6 31Pand'J(PN) while two dimensional spectra give 6 15N.4Phosphorus-31 and nitrogen-15 NMR data are also available for ArN=PN=P(NMe2)3.5Dipole moment studies of o-X-C6&N=PPh3 (X=H,Me,Et,OMe,OEt) lead to assignment of PN bond polarity of 3.6 Debyes.6 Gas-phase basicity, proton affinity, values of Schwesinger phosphazene super bases have been obtained and correlated with solution (in acetonitrile) pKa studies.' The course of the imideamide rearrangement of trialkyl(ary1imido) phosphates has been followed using GC-mass spectrometry.' The mass spectrometric fragmentation patterns of C6H1lP(SMe)NMe=NS02C&14R(R=H,Me,Cl,Br,F,OMe) have been established with the aid of high resolution data and metastable analy~is.~ Before consideration of specific acyclic phosphazene syntheses and reactions, the synthesis of certain phosphazene precursors or related products bears mention. A noteworthy example is the tetraaminophosphonium ion. The reaction of PC15 with liquid ammonia gives P(NH2)+4Cl-lo~ll while the corresponding 285

286

Organophosphorus Chemistry

iodide is obtained from a two step sequence in which (NH2)3PSis treated with methyl iodide followed by ammonia." The structure and MO calculations suggest nitrogen lone pair donation to phosphorus. The reaction of P(NH2)4+CIwith PC15 gives P(N=PC13)4+ which undergoes ammonolysis to the Pp=P(NH2)&+ ion. Heating of P(NHz)~+C~with CoCl2 to 800" give the phosphorus-nitrogen sodalite cage C07[P12N24]C12. The phosphazene hydrolysis product diimidotriphosphoric acid, (HO)2P(0)NHP(O)OHNHP(O)(OH)2, can be obtained by catalytic hydrogenation of a precursor protected at both the -OH and -NH ~ i t e s . ' ~ . ~ ~ New information about the classical Staudinger reaction has been obtained. Monitoring of the reactions of different azides (RCH2N3 (R=l), a-azido-o-xylene) and phosphines (PhSP, tri-2-furylphosphine) with NMR and other spectroscopic techniques shows the initial formation of the triazaphosphadiene (RN=N=N-PR'3 ) which can either undergo the expected decomposition to the phosphazene or itself be the origin of the follow-up reactions with acylchloride or HCI. Approximate rate data is available for certain of these reactions.l4 An unexpected Staudinger reaction occurs in the treatment of u-azidophenylacetonitrilewith triphenylphosphine. A half molar equivalent of phosphine yields PhC(CN)21-Ph3PNH2+ while two molar equivalents of phosphine gives a mixture of PhC(CN)=NN=PPh3 and Ph3P=NH.I5 A series of phosphites (Ph0)3-~x+,~(MeO)x(CF3CH20),PP may undergo polymerization during the Staudinger reaction with Me3SiN3. No polymerization occurs in the absence of a phenoxy group. Isomerization of the phosphoranimine to a phosphoramidate, (PhO)(RO)P(0)N(SiMe3)Me occurs for all species except (Ph0)3P and (CF&H20)3P. A linear relationship between31P NMR chemical shifts and the pKa of the parent alcohols of the phosphite has been noted and it was shown that isomerization is decreased by electron donating substituents.l 6 Ortho and meta-phthalimidobenzoic acid azides have been converted to phosphazenes via the reactions of trimethylphosphite or tris(dialky1amino)phosphines. l 7 The diazocarbonyl derivatives, RC(0)C(N2)C(O)R (R=alkyl, aryl; R'=CF3,C3F7) combine with triphenylphosphine to give phosphazenes.l8 The more extended nitrogen-nitrogen multiple bonds in 2 react with P(OEt)3 to give triethyl(2-pyridylimido)phosphates, RC5NH~N=P(OEt)3. Spectroscopic and potentiometric studies of protonation of the phosphazene have also been examined.l 9 Sulfamoylazide, NH2S02N3, undergoes the expected Staudinger reaction to give Ph3P=NS02NH2.20The dinucleotide phosphazene derivative, (N)2P(NHCH2CH20CH20Me)=N(CH2)20CH20Me (N=nucleotide), has been prepared.21Cryptands have been attached to phosphorus based macrocycles via construction of phosphazene linking substituents.22

7: Phosphazenes

287

Other synthetic methods for preparation of acyclic phosphazenes based on phosphorus precursors in various oxidation states are available. Sequential treatment of chloramines with R2PC1, NH3 and C12 generates chain extended phosphazene chloramines. Thus Ph2P(0)N(Cl)H is converted to Ph2P(O)N=PR,N(Cl>H which in turn goes to Ph2P(0)N=PR2N=PR21N(C1)H.23 Phosphine oxides, R3P0, when subjected to sequential steps of triflic anhydride, ammonia and evaporation followed by recycling through the process ves hi h yields of R ~ P z N H . Reactions ~~ of bromophenyldiazirine, Ph (Br)N=N, with phosphines represent a novel pathway to selected acyclic phosphazenes. Alkyl, aryl and mixed phosphines give the cationic species PhC(NPR2R’)2+Br-. Use of R2PSnMe3 [R = (ipr)2N] leads a complex mixture including R2P(Br)= NSnMe3 and cyclic species (see section 4). In the presence of ClSiMe3 the trimethylstannylphosphazene is converted to R2P(Cl)=NSiMe3.25Oxidative coupling of (Ph2P)ZNLi with anhydrous FeF3 gives Ph2PN=PPh2PPh2=NPPh2.25 The addition of RN=C=NR to (R0)2PNHR’ gives (R0)2P(=NR”)C (=NR)NHR which undergoes dealkylation upon treatment with (R0)2P(S)SH to give the Zwittertonic product 3.” Dialkyl(silylamino)phosphines, R2PNT2 (T = SiMe3), undergo nucleophilic oxidative addition to alkynes. With phenylacetylene, TH2C(Me)P(=NT)CH=CHPh and Et2P(=NT)CH=C(T)Ph are derived from the methyl and ethylphosphines respectively. Both phosphines give R2P(=NT)CH=CT2with trimethylsilytlacetylene. The presence of 0x0 functions allows for trimethylsilyl transfer to formation of OSiMe3 substituents, in addition to the phosphazene moiety, in reactions of PhC=CC(O)H and PhC = CC(0)Me.28 Oxidative addition with Me3SiC1 elimination occurs in reactions of R2PNT2with R’R2PCl to yield R2P(=NT)PR’R2.Addition of sulfur effects a second oxidation giving R2P(=NT)P(S)R’R2.29Iminophosphines, ) under 2 + 1 cycloaddition RP=NAr (R=CMe3,Ph,C1;Ar=2,4,6-(Me3C)3C6H2 reactions with alkynes, R’CCX (X=OR, NRZ2,H)to give 4. Competitive reactions such as 2 + 2 cycloadditions (X=NR22)or addition of C-H to P=N (X = H) are also In the aminoalkynes, the 2+1 process is favored by increased size of the dialkylamino group and decreased size of the phosphorus substit ~ e n t . ~The l ClP=NAr species reacts with RC=COR’ to give an intermediate EtOC(Cl)=C(Me)P=NAr-which goes on to form 4.32 Depending on the R substituent, addition to EtOC = CH gives RtP(+NR2)P(=NR2)R’C(OEt)=CHor HC = CPR(OEt)=NR2.30-33More complex reactions are obtained with silyliminophosphines, R(Me3Si)NP=NR (R=Me3Si,Me3C) where 2+2 cycloaddition to non-phosphazenes (azaphosphetines) are favored. Addition to Me02CC= CC02Me gives a dioxadiphosphabicyclooctadiene with exocyclic phosphazene units.33Reactions of 4 with polar reagents leads to ring cleavage except for HCl and HBr which add to the phosphazene. Addition of BuLi gives Me3CP(=N)(BU)C=CCE~.~ Oxidation of P4 by 0 2 in the presence of RNH2, I2 and NaN02 gives (RNH)3P=NR.35 Reactions in which the phosphazene bond itself undergoes reaction have become standard and important tools in organic synthesis. Reaction of 5 (X=Y=OEt) with R3P=NSiMe3 (R=Bu,NMe,Ph) gives rise to 5 (X=OEt,NEtZ, NPR3;Y=NPR3) which add isocyanides to give 5(X=NPR3;Y=NCNPh).36Phos-

F

288

Organophosphorus Chemistry

phonioquanidines, [R’Ph2PN=C(NH2)NHR]+Cl-, are obtained from the interaction of RPh2P=NCN with RNH3+C1-.37Propargylbromide can be converted to (Et0)3P=NCH2C=CH by standard Staudinger procedures. Reaction of RMgBrl CuBr with the phosphazene gives (Et0)2P(0)NHCH2C(R)=CH2which after acid hydrolysis and neutralization gives allylalkylamine~.~~ Treatment of RCH2PPh2=NC02Mewith n-butyl lithium and dimethylacetylenedicarboxylate gives Rk=PPh2NHC(0)C(C02Me)=k(C02Me)presumably through tautomerization of a phosphazene amineylide intermediate.39 Acylchloride adds to 3-triphenylphoranimino-~-lactam~.~ The Staudinger reaction of N-(0-azidobenzoy1)-a-amino acids is followed by an intramolecular aza-Wittig step leading to 1,4-benodiazepin-5-0ne derivative^.^^ Diazosuccinimides add triphenylphenyl phosphine at the azo function to yield RfiC(O)C( =N-N=PPh3)C(O)c(O) which undergo phosphazene hydrolysis to give hydrazones or can add species such as diethyl acetonedicarboxylate or ethylacetonate to give pyrrolo[3,4-~]pyridazines (6). These species may be obtained from intramolecular aza-Wittig chemistry of R&C(0)C(=NN=PPh3)C(=CC02R)k(O).42 Bistetrazolo[13-a:5,l -c]quinoxaline with an azide P to the tetrazole reacts with triphenylphosphine to give products in which the azides are replaced by phosphazene moieties. Hydrolysis leads to 4aminotetrazolo [1,5-a]-quinoxalineand 2,3-diaminoquinoxline respectively. Use of dilute hydrochloric acid gives the tetrazole with a 4hydroxy s~bstituent.4~ Vinylimino-phosphoranes have proven to be especially valuable precursors in ma-Wittig chemistry. Aldehydes with aromatic or vinylic functions add to Ph3P=NCH=CHC02Et via nucleophilic attack on the P-carbon of the olefin followed by cyclization to pyridines and/or dihydropyridines.44Different reaction sites have been observed in the chemistry of Ph2RP=N(CH2R)=CHP(0)Ph2. Carbonyl compounds R2R3C0 (R2,R3=Me,CN,C02Et) attack the y-carbon atom of the olefin giving R2R3(HO)CCHRC(N=PPh3)=CHP(0)Ph2 which upon hydrolysis convert the phosphoramine to an amine. By way of contrast, an azaWittig reaction occurs with ethyl glyoxalate to give (Et02C)CH=NCMe=CHP(0)Ph2.45 Phenyl substituted Sazaazalene derivatives, 7, are easily prepared from PhC(N=PPh3)=CH2and 5-(dimethylaminomethylene)cyclopenta-1,3-dienecarbaldehyde via an ma-Wittig process. In the absence of the a-phenyl group in the vinyl(imin0)-phosphorane, an alternative pathway is followed providing a cyclopentadiene with adjacent CH=O and =CHNH2 moieties.46The addition of PPhJCzCldEt3N to 3-aminopyrazine-2-amidesallows for conversion of the amino to a Ph3P=N function which undergoes an intramolecular aza-Wittig reaction to give pyrazino [2,3-e][1,4] diazepine-5-one (8).47Butyl alcohol reacts with Cl3PNP(0)Cl2 to provide (RO)(RO)P(0)NHP(O)(OR)(OR)?8 The very

7: Phosphazenes

289

R*FL0 R"

\

0

N I

OMe (7)

(8)

strong, non-nucleophilic bases, e.g. Me3CN=P[N=P(NMe2)3],continue to attract extensive interest for catalysis of a variety of chemical processes. Examples of these applications include anionic ring-opening polymerization of ethylene oxide in the presence of butyl ring opening polymerization of lac tarn^,^^ step polymerization of polycarbonates from bisphenols and aryl~arbonates,~~ improved distereoselectivity in the addition of a-sulfonyl carbanions to butyraldehyde and isopropylidene-gly~eraldehyde,~~ formation of isocyanates from C02 and primary a ~ n i n e sand ~ ~ initiation of ring-opening polymerization of (Me2Si0)4.s4 Cations such as [Me2N)3P=W4P+and Lewis acids catalyse the isomerization of vinyloxirane and its alkyl derivatives to 2,5-dihydrof~rans.~~ Acyclic chlorophosphazenes of the types C13PN(PC12N),PC13+PC16- and C3PN(C12PN),P(0)Cl2 have attracted considerable attention for use in equilibration andor condensing of s i l o ~ a n e s . ~Phosphazene ~ * ~ ~ * ~ ~capped siloxanes have been identified.59Other applications include equilibration of linear and disiloxanes to give low molecular weight species,60disproporation of higher siloxanes to lower species,61cross-linking by equilibration with polyfunction siloxanes62and stabilization of siloxanes with phosphazene catalyst residues with non-basic solid

absorb ant^.^^ The synthesis of new phosphazenes by transfer of an intact phosphazene unit from one center to another or reaction at a site separated from the phosphazene presents alternative, widely utilized synthesis pathways which have found particular application to inorganic systems. The siloxane chemistry summarized above may represent, in part, examples of this methology. Metallation of Me3SiNPMe3 and Me3SiNP(ipr)3 with n-BuLi give [Me3SiNPR2CR2lLi]4 (R =Me,R =H;R' =ipr,R=CMe2).64 0ther phosphoranimine organolithium reactions give metallacyclic structures (Section 5). The free [Me3SiNPPH2S]- anion can be obtained from the reaction of Ph2P(S)N(SiMe& with KOCMe3 followed by methathesis with AsPh+Cl- .65 1,4-c6F4(CN)N3reacts with Ph3P=NSiMe3to give 1,2,4-C6F3(CN)(NPPh3)N~.66 Phosphoranimine transfer from Me3SiNPPh2Rto I , ~ - C S F ~ ( Coccurs N ) ~ in a stepwise fashion at the 4 and 6 positions leading to symmetrical, 1,3,4,6-C6F2(CN)2(NPPh2CH2PPh,),, and unsymmetrical, 1,3,4,6-C6F2(CN)2(NPPh2CH2PPh2)(NPPh2R) (R=Ph,Me) derivative^.^^ The first bridging dithioimidodiphosphinato complex, Me3SnSPPh2NPPh2Sln based in trigonal bipyramidal S2SnC3units with sulfur atoms in the axial sites has been characterized.68 The reaction of S2C12 and Me3SiNPMe3 gives

290

Organophosphorus Chemistry

S(NPMe3)4C12which contains the S(NPMe3)42+dication. The structure has been modeled by ab initio calculations on S(NPH3)42+.69 As an indicator of how subtle changes in the reaction can result in different products, the analogous reaction with SC12 gives S(NPMe3)3+C1-.70 A similar product, S(NPPh3)3+ C1-, is obtained from S3N2C12 and Me3SiNPPh3 while the selenium analog Se(NPPh3)3+Cl-, is available from SeCL.,.70 If thiazylchloride, (NSCl)3is used as the sulfur substrate, (Me3PN)3SNS(NPMe3)22+ is isolated as the dichloride salt.71 The phosphazene RP(SH)NR2=NS02C6H4X is a minor tautomer of RP(S)NR2NHS02C6H4X. In the S-methyl derivative, RP(SMe)NR2=NS02 C6H& the phosphazene is fully realized. These compounds have been evaluated for inhibitory action on carbonic anhydrase and selected bacterial strains.72 Interhalogens form phosphoranimine donor-acceptor adducts, e.g. Me3SiNP MepICl from E l ; which has a weak N/I interaction. When IC13 is employed Ph3PNCl.ICl is obtained from Ph3PNSiMe3 and the hydrolysis product, Me3PN(H)PMe3I2+[IC1-l2,is formed from Me3SiNPMe3.73 Transition metal systems have also been explored in some detail. Treatment of TiF4 with Me3SiNPPh3 gives [TiF@JPPh3)(HNPPh3)]2, a fluorobridged dimer with additional NH-F hydrogen bonding in axial positions connecting the edge sharing octahedra.74 The reactions of Me&NPR3(R=Me,Et) with MC12[M=Cr(THF)2,Cu, Pd] lead to MC12(Me3SiNPR3) (M,R=Cr,Me;Pd, Et) and [ C U C ~ ~ ( M ~ ~ S ~ N P Monodentate, M ~ ~ ) ] ~ . ~ ~8-N, behavior is observed in the coordination of CHMe(Ph2P=NC6H4-p-Me)2 to [PtC12(PR3)]2 to give C12P(PR3)N(Ar)=NPPh2CHMeNPPh=NAr (R3=Et3, Me2Ph)76 and iminophosphanano-pho~pholes.~~ Addition of Cp2Zr(H)C1 to P(NR&NH2 gives (R2N)2P(H)=NZr(C1)Cp2.78 The phosphinimine, ClP=NAr [Ar=2,4,6-C6H2 (CMe3)3] combines with Cp2ZrMe2 to give Me2P(ZrCp2C1)=NArwhich is in equilibrium with the ionized form [Me2P=NAr]l-CpZrCl+, Insertion reactions with paraformaldehyde, CS2, RR’PCl and isonitriles give a variet Me2P(X)=NAr (X=CH20ZrCp2Cl; PRR’, Cp2 r(Cl)+-NR= derivative^.^^ The nitrido ligand can behave as an electrophile in a reactions with Bu3P to give Bu3P=NMo(TPP) (TPP= tetraphenylporphyrin).80 A linkage isomer, Mo(PNM~s)(A~(R)N)~, of the phosphoranimino ligand can be prepared by reaction of the phosphido complex, (Ar(R)N)3MoP,with mesityl azide.sl The reactions of Ph3P=NSiMe3 with cationic gold species, (Ph3P)Au+BF4- or (Ph3P)Au)30+BF4- give di- and trinuclear cationic complexes, e.g., Ph3PN(AuPPh3)2+BF4-and ph3PN(AuPPh3)2]3+BF4-,in which the gold units cluster about the imine nitrogen center.82First row transition metal ions can be extracted into organic solvents using 1-o-tolyl-2,2’-dianilino-2-(N-phenylthiourea)- monophosphazene. Thermodynamic parameters for the process have been obtained.83Additional reports of phosphoranimine metal complexes as part of metallocyclicspecies may be found in Section 5. Miscellaneous applications include coating compounds formed by UV irradiation of (CH2=CRC(O)OCH2CH20)3P=NP(O) (OCH2CH20C(O)CR=CH& 84 and the use of [ph2P(R)IN=P(R)Ph2]+X- @=halide, BF4, BPb;R-C,-, alkyl, Ph) as antiflouling coatings exhibiting low

m,

4;

7: Phosphazenes

3

291

Cyclophosphazeaes

Reviews of cyclophosphazene chemistry have focused on several important subtopics rather than comprehensive surveys or overviews. A comprehensive review of polymers derived from addition polymers of olefins attached to cyclophosphazenes has appeared. Synthesis, copolymerization and quantitative studies of monomer reactivity are discussed in A comprehensive two part review of hybrid phosphazene-siloxane systems includes cyclophosphazenes with siloxane ~ubstituents~~ and polymers derived from hydrosilation of alkenylphosophazenes.88A survey of new generation candidates for currrently banned Halon fire extinguishing agents concludes that phosphazenes are superior to halons in lab scale extinguishment tests.89 Theoretical calculations and physiochemical measurements on cyclophosphazenes continue to attract interest. Force field parameters for aryloxylclotriphosphazenes have been calculated using SCF calculations (4-31 G*). The calculated and observed structure of N&(OPh)6 were in reasonable agreement.g0 NMR spectroscopy is a major area of focus. Algebraic equations for complex spin systems have been developed which could be used for the deceptively simple spectrum of N3P3(0Me)6.91Variable temperature 31P NMR of N3P3(NHPr)S N=P(NHPr).HCl shows intromolecular proton exchange from endocyclic sites.92 A series of one and two dimensional NMR experiments have been used to generate3'P and15N shifts and coupling constants for a few selected aryloxyphos~phazenes.~* 93 Solid state MAS 31PNMR data for N3P3X6 (X=F,Cl,Br,OMe,NH2) show that the tensor perpendicular to the PC12 planar varies widely with X.94The liquid crystalline behavior of several hexaalkoxy and biphenyloxy cyclotriphosphazenes with substituents terminating in long chain alkyl groups has been e ~ a i n e d .Techniques ~ ~ - ~ ~ employed include DSC,95-97polarizing microscopy95-97FTIR spectroscopyg5and X-ray measurement^.^^ Large spontaneous polarization was observedg6and IR evidence suggests changes in the ring occur near the crystalline to smectic phase t r a n ~ i t i o n .The ~ ~ shape of the phosphazene ring appears to play a major role in the stability and behavior of the mesomorphic p h o s p h a z e n e ~ .A~ ~detailed ~ ~ ~ report on the chemical resistance of the hard coatings obtained from polymerization of the commercial product N3P3(OCH2 CH20C(0)CMe=CH2)6is a ~ a i l a b l e . ~ ~ The syntheses of cyclophosphazene rings by new routes have been reported. The aminohydrio derivatives [P(H)NR2N], (n=3, cis and trans; 4) can be obtained from elimination reactions of P(NR2)2NH2 or (R2N)2P(H)= N Z ~ ( C ~ ) CAP very ~ . ~ promising ~ synthesis of arylphosphazenes by the reaction of Ar2P(0)NH2 with PPhdCClJEt3N appeared in a preliminary communication. Hexaaryl derivatives N3P3Ar6 (Ar=Ph, 2-C5H4N and 2-C4H3S) as well as spirocyclic species involving 2,2'-biphenyl substituents and 9 can be obtained using this rou@ et'. ' The reactions of halophosphazenes with nucleophiles continues to be utilized as one of the major routes to new cyclophosphazene derivatives. Fluorophosphazenate anions are obtained by the reactions of fluorocyclophosphazenes with (Me2N)3S+Me3SiF2lW, an effective fluoride ion donor. The trimer yields 10 as the

292

Organophosphorus Chemistry

2-

[(Me2N)3S+]2salt. This material is a model for the first product in the ring opening polymerization of cyclotriphosphazenes.lol The reactions of (NPF2), (n=4,5,6) lead to fluoride addition to one of the phosphorus atoms in the ring to provide the (NPF2),-1NPF3- anions. These products are models for intermediates in S N ~ ( P )reactions of cyclophosphazenes. NMR spectroscopy shows rapid fluoride ion exchange in solution.lo2 Amino derivatives include the series N3P3c16_,[N(Me)CH2C5H4FeCp], (n= 1-4) which are available from the ferr~cenylamine.’~~ The spirocyclic derivatives N3P3F4(NRCN2CH2NR) (R=H,N02) and N3P3F2[N(N02)CH2CH2N(N02)] have been prepared. The nitro compounds are of interest as energetic materials.*@’ The reactions of N-methyl-1,3-diaminopropanewith chlorophosphazene give the spirocyclic derivatives, N3P3C16_2,[N(Me)CH2CH2NHIn (n-l,2,3) and N3P3PhQ-2,[N(Me)CH2CH2NHIn (n= 1,2). Additional substitution reactions give N3P3R4p(Me)CH2CH2NH](R=NMq,0Ph,0Me,0CH2CF3).lo5 The ansa, i.e. 2,4 bridged, structure is obtained in the reaction of NH2(CH2)30Hwith N3P3Cl6 to give 2,4-N3P3Cl4W(CH2)30]. The structures of this derivative and the previously reported 2,2’,4-N3P3(Me)C13[NH(CH2)30] have been modeled using the molecular mechanics approach employing a locally derived force field.lo6 The Gd chelate of N3P3Rs (R=ll) has been prepared and enzymatic hydrolysis studied. Elaboration to dendrimeric derivatives is also possible.lo7 Long-chain diamines add to N3P3C16 to give N3P3pH(CH2),NH2]s which in turn can add N3P3C16 to give the first generation dendrimer The process has been repeated up to the eighth generation.lo8The reactions of organooxyanionslead to the largest number of new cyclophosphazenederivatives via the nucleophilic substitution route. Reactions at the interface of two liquid

-NHCH2CONH(CH2)2NHCSNH

HCO: (1 1)

‘CQH

7: Phosphazenes

293

phases lead to changes in the cidtrans isomer ratio in bis(ary1oxy) cyclotriphosphazenes.lW Long chain hexasubstituted cyclotriphosphazene derivatives with 4-penten-2-yn-1-yloxy and 4-methyl-4-penten-2-yn-1 -yloxy substitutents' lo as well as the OCH2CH2N[CH2(CH20CH2)nCH2OR]2 (n=3,R=Bu;n=4,R=ldodecy1)ll' have been reported. The latter have been used as phase transfer catalysts.ll' A preliminary report of a series of new methacyryl phosphazene derivatives, N~P~C~SO(CHR)~(CHR'),OC(O)CM~=CH~ (x=y=l,IL,R=R'=H; x=l,R=Me, y=l, R=H; x=l, R=H, y=l, R'=Me) as well as spirocycles with methacyryl side chains and the norbornene-Zmethoxy derivative have been prepared.lo3 Derivatives obtained by reaction of 2-hydroxyethyl methacrylate with N3P3F6followed by polymerization of the methacylate give dental resins which allow for slow release of fluoride ions.112Most of the organoxyanion derivatives are aryl derivatives. High yield syntheses of N3P3(OC6&R)6 (R=Br, CN, CHO, COMe, COPh, N02) from the parent phenols has been presented.l13 A series of fused ring aryloxy derivatives [NP(OR)2]n (n=3,4) where R=l- or 2naphthyloxy, 1-napthylmethoxy, 1-naphthylethoxy, 9-anthryloxy and 9-phenanthryloxy as well as the partially substituted, N3P3(0R)ClSand N3P3(OR)&12, have been prepared. The crystal strucures of many of these materials were also reported. l4 Hexasubstituted,N&(OR)6, derivativeswhere OR=4-(4'-heptyloxy)b i p h e n o ~ y ,4-(4'-(6-methyl)octyloxy)biphenoxy,g6 ~~ 4-(4'-alkyloxybiphenoxy)100 and relatedg7 materials have been prepared for liquid crystallinity studies. Detailed and fascinating spirocyclic derivatives derived from oxyanions have appeared in this time period. The sequential reaction of the disodium salt of dihydroxy-1,I-biphenyl and K+OC6H4N02followed by reduction of the nitro group gives 12 in which two different conformations of the spiro groups are inferred from the 31PNMR s p e ~ r u m . The ' ~ ~ reactions of NaO(CH2CH20),Na with N3P3C16 yield 13 and 14 (X=Cl; n=4,5) which may be separated by column chromatography. The ansa compound (13) is stable while the spiro isomer (14) is reactive to decomposition. The one-pot in situ phenolysis or naphtholysis of the choloro precursors noted above gives high yields of 13 and 14 where X=aryloxy units. The facile chlorine substitution of 13 and 14 (X=Cl) is believed to be facilitated by the phosphazene polyether derivative acting as a crown ether and coordinating the sodium cation.'16 The reaction of 13 (X=Cl; n=4) with the

294

Organophosphorus Chemistry

disodium salt of bi-Znapthol gives rise to two transannular bridge arrangements of the 2,2'-dioxy-l,l-binapthylunit, a 2,4 bridge (i.e. between the two substituted phosphorus atoms (13)) and a 2,6-bridge (i.e. between a substituted phosphorus atom and the free =PC12 center in 1 3 ) . l 1 7 p 1 1 8 On the other hand, diamines, NH2(CH&NH2 react with 13 (X=Cl, n=4) to provide molecules where the diamine bridges two different molecules of 13 by reaction of only one of the substituted phosphorus atoms. l8 Cesium fluoride catalysed trimethylsilyl fluoride elimination from bifunctional trimethylsilyl ethers, thioethers and dithioethers in the presence of N3P3F6 gives rise to spiro fluorophosphazenes, monodentate or bridged derivatives. The use of Me3SiX(CH2),SSiMe3 gives the spiro derivatives N3P3F4m(CH2)nS] @=O, S; n-2,3) in which the 31PNMR spectra show a large dependence on ring size. When (Me3SiOCH2CH2)20is employed, a monodentate ('dangling') product N3P3F50CH2CH20CH2CH20SiMe3 is obtained which under more forcing conditions leads to the intermolecular bridged species N3P3F~O(CH2)20(CH2)20N3P3F5. A perfluoro species m3P3F50C(CF3)2]2C6F4 is obtained from bistrimethylsiloxy precursor. Aromatic disiloxanes can be used under mild conditions to give the monospiro derivatives of 3-fluoro-1,2-catechol, 2,3-napthalenediol and 2,2'-biphenol and the dispiro derivative of the biphenol. Replacement of the remaining fluorine atoms of the mono spiro derivatives can be accomplished using the 0-,m- or p- FC6hoSiMe3 reagents.l19 Synthetic transformations of exocyclic groups on the cyclophosphazenes is the other major synthetic pathway to new cyclophosphazene derivatives. The hydrazinophosphazene, N3P3(NMeNH2)6 can be transformed to hydrazones, N3P3(NMeN=CHAr)6,spirocyclics (15) and small dendimers.120 Phosphazene bound Wittig reagents, N3P3(0Ph)50C6&PPh2=CHR can be obtained from N3P3(OPh)50C6'H4PPh2.121 A considerable amount of the effort in this area involved preparation and polymerization of exocyclic functionalities to yield phosphazene containing polymers. Polymers with phosphorus-nitrogen backbones (polyphosphazenes) are discussed in Section 6. The reaction of CH2=CHOCH2CH20Na with N3P3C16 produces N3P3C12(0CH2CH2-(OCH MeOCH2CH2),0CH=CH2)4 (n=0-8 with n= 1-3 predominating).'22* The sequential addition of vinylbenzylmagnesium chloride and methyl iodide to

7: Phosphazenes

295 Me N , -NH

Me

N3P3( NMe l Nl&HzPPh)3

(15)

N3P3C16 provides the monomer 2,2'-N&Cb(Me)CH2C6H4CH=CH2 which undergoes radical initiated copolymerization with methylmethacrylate (MMA). Reactivity ratio data shows a small effect of the phosphazene on the 01efin.l~~ Methacryl chloride combines with N3P3Cb(R)H (R=ipr) to give 2,2'N3P3C14(R)C(O)CMe =CH2 and the novel side product, N3P3Cl4(R)I2CMe(OH). Treatment of N3P3C4(R)CMeOHwith C1SO2CH3also yields an olefin monomer, 2,2'-N3P3Cb(R)C(Me)=CH2and the curious ansa (2,4) bridged material 2,2',4N3P3C13(R)[CMe2CH=CMeO]. Neither of the two olefin monomers undergoes homopolymerization. Low phosphazene incorporation can be achieved in copolymerization with MMA and somewhat higher incorporation can be attained with styrene as the c o m ~ n o m e r . The ' ~ ~ addition crown ethers and azacrowns to the LiC104 complex of [CH~CH(C~HSON~P~(OCH~CH~OCH~CH CH20Me)5], has been examined in terms of variation of T, and ionic conductivity with 3.5-7 fold increases in conductivity being obtained.125 Hexakis (4-ethynylpheno~y)'~~ and hexakis (4-ethynylanilino)cyclotriphosphazene126~127 can be thermally polymerized (at the exocyclic position) to yield cross-linked materials with high thermal stability. The amino groups in 12 can be acylated with acetic anhydride or treated with 3,3',4,4'-benzophenonetetracarboxylic acid or 4,4'-hexafluoroisopropyllidenediphthaticacid to give poly(amidic acids). The cyclodehydration of the poly(amidicacid) gives rise to polyimide films with high thermal stability.' l 5 Related studies involve the conversion of N3P3(0Ph)4(0C6H4NH2)2to polyimides by treatment with dianhydrides (3,3',4,4'-benzophenonetetracarboxylic dianhydride and 3,3'-4,4'-diphenylsufone tetracarboxylic dianhydride) to give poly(amidic acids) which upon heating give the thermally stable, fire resistent polyimides.12* Poly(urethanes) with cyclophosphazene substituents can be obtained from a multistep route starting from N3P3(0Ph)5Cl. The sequential addition of NaOC6H3-3,5-(OMe)2 followed by demethylation with BBrdH20 gives the diol component, N3P3(OPh)5 [OC6H3(0H)2] which, when combined with diisocyanates, gives the expected poly(urethanes).129~130Exocyclic reactions with a more inorganic focus have also been agressively pursued. An interesting observation is the deprotonation of all six NH units in N3P3(NHCsHll)a by butyl lithium to give the N3P3(NC6H11)66anion.13' Siloxane chemistry on a cyclophosphazene core continues to appeal to researchers in the area. Treatment of N3P#& with NaOSiPh3 gives 2,2N3P3C4(OSiPh3)(ONa) and 2,2-N3P3Cb(ONa)2 which upon treatment with ClSiPh3 gives 2,2,N3P3C14(0SiPh3)2. If N3P3(0Ph)~Clis treated with Et3SiONa followed by Ph3SiC1, N3P3(0Ph)sOSiPh3is obtained. Cleavage of carbon-oxygen bonds can also be effected by reactions of N ~ P ~ C ~ S Oand B U N3P3(OBU)6 with Ph3SiC1 to give N3P3C150SiPh3 and N3P3(0SiPh3)6.132The reaction of 2,2-

296

Organophosphorus Chemistry

N-N

N3P3C14(NH2)2 with HN(POC12)2 leads to [N3P3(H)C4(NH2)2]+NP(OC2)2- in which an endocyclic nitrogen atom is ~ r o t 0 n a t e d . l Metal ~ ~ complexes of the cyclophosphazenescontinue to be the most actively exploited inorganic chemistry of the preformed phosphazene derivatives. Both exocyclic and endocyclic centers can serve as the ligand sites in these complexes. The pyrazoyl moiety has proven to be the basis for an effective ligand system when attached to cyclophosphazenes (as in la). The reactions of the hexa(3,5-dimethyl-pyrazoyl)cyclotriphosphazene, Cu(I1) halide complexes, 16.CuX2 (R=Me; R'=3,5-dimethyl-pyrazoyl;X=C1, Br) with M(PhCN)2C12 (M=Pd,Pt) gives rise to the bimetallic complexes, 16.CuC12MX. Electronic and ESR spectroscopy along with X-ray crystallography show Cu(I1) to be in a distorted trigonal bipyramidal environment involving two non-geminal pyrazoyl nitrogen atoms and an endocyclic nitrogen atom while Pd,Pt are square planar with a cis array of two geminal pyrazoyl nitrogen atoms.'" The anhydrous metal halides MX2 (M=Cu, X=Cl, Br; M=Co, X=C1) add 16 (R=H;R=Ph) to give 16.MX2. The structure of the Co(I1) complex also has the distorted trigonal bipyramidal motif noted above for the Cu(I1) bimetallic species. 135 The N3P3(0Ph)6-,(NHR), (R=alkylpyridine; n= 1,2,6) derivatives have been prepared. The monosubstituted (n= 1) species (L) functions as a multifunctional donor in the C U L ~ ( N O ~ ) ~ C O ( L ( Nand O ~ ) PtLCl, ~ ~ornp1exes.l~~ The 2- and 4-hydroxypyridines react with N3P3C16 to form N3P3(OC6]H4N-2)6 and N3P@C6H4N-4). The 4-substituted derivative reacts with fa~-[MN(OC10~)(CO)~bipy] to form the hexacationic complex, [N3P3(OC&4)Mn.(CO)3(bipy)]6(C104)6. Stable complexes are not obtained if the 2-substituted cyclophosphazene is employed as the ligand.13' The cyanophenoxy phosphazenes N3P3(OC6H4R)5OC6&CN (R=H, CMe3) and N3P3(OC&CN)6 coordinate to tran~-MnBr(CO)zL[P(OPh)3](L=Ph2P(CH2),PPh2 n= 1,2) through the nitrile unit. Spectroscopic and electrochemical data are reported for the complexes.138 The interaction of H ~ ( O A C )with ~ N&(NH2)6 has been examined,139 Stable 1:2 lanthanide (Er3+,Tb3+)complexes of hexakis (4-carboxy1atophenoxy)-cyclotriphosphazene have been prepared and their fluoroescence behavior examined. Several applications oriented publications, particularily in the patent literature, involving cyclophosphazenes demonstrate the ongoing interest in finding new uses for these materials. A new emphasis is in the use of phosphazene lubricants on hard metal surfaces and their tribological behavior. 141-143 Uses suggested include elevated working t e m p e r a t ~ r e , ' ~ ~ ~oxidation ' ~ ~ * ~ ~resistant'43 *~~~ and high

7: Phosphazenes

297

h ~ m i d i t y ' ~situations. J~~ A model for boundary film formation in these materials has been established.143 Cyclophosphazeneswith polymerizable substituents, the most common being the hydroxymethylethacrylate function, have been employed as curable components for thin protective layers. 149-154 Curable aminophenoxy phosphazenes give polyimide coatings. 55 Hydroxyorgano groups react with epichlorohydrin to give curable expoxy layers. 56 Reactions of chlorophosphazenes and siloxanes are catalysts for hydroxy-cyclosiloxane polymerization (see also Section 2).157-158 As always, flame retardent phosphazene based materials are a focus of attention.161-164 4

Mixed Main GroupPhosphazeneRing Systems Including

Cyclophospha(thia)zenes

This section covers systems in which there is at least one phospha(V)zene moiety in an otherewise carbocyclic or heterocyclic ring system. A class of 4~-electron, four member phosphazene heterocycles, 1,2-h5-azaphosphetes, R2b=N-CCR=(kR') are available from a variety of precursors. These routes include treatment of R2PC(SiMe3)CPh=& with Ru(I1) and thermolysis =N N=N-CCR)=dR. The related 1,3,2-h5-diazaphosphetes, R2l -N-CPh=N, Of P + along with low elds of R2kNCPh=NCPh=fi can be obtained from the reaction of Ph (Br)N=N with R2PSnMe3.25*165 Molecular orbital calculations suggest a zwitterionic structure for the 1,3,2-h5system with the negative change in the NCN allylic fragment and the positive charge on the phosphorus atom. Reactions of the 1,3,2-h5diazaphosphetes can result in the ring retention or opening. Hydrolysis gives R2P(0)N=C(MH2)Phwhile benzaldehyde treatment provides R2P(0)N=C(Ph)N=C(Ph)H. Lewis base behavior is noted in the addition of methyl trifluoromethanesulfonate which gives a mono adduct P&(Me)CPh=N+OTf- or BH3.0Et2 to give the diadduct R2 -N(BH3)CPh=NBH3. Ring expansion to the 1,3,4h5-diazaphosphinine R2&NC(Ph)=NC(C02Me)=&02Me occurs. The reactions of triazaphosphinine (ipr2N)2h=N-N=N-C(C02Me)=k(C02Me) with metal complexes, e.g. PdCI2(PhCN)2and W(CO)5THF,give the simple 1:l adducts in which a nitrogen atom functions as a q' Lewis base.165p167Nitrogen elimination from these complexes leads to complexes of the 1,2-h5-azaphosphetesin which the unique nitrogen atom acts as the Lewis base. In the case of M~(CO)~(pip)~(pip= piperidine), addition of the triazaphosphinine leads to the expected 1:l adduct in which one piperidine is displaced. Slow transformation of this complex leads to a MO(CO)~adduct of the new five membered ring 17 in which the endocyclic nitrogen atom acts as the Lewis base. If two equivalents of W(CO)5pip are added to the triazaphosphinine, W(CO)5pip.17 is formed in which the piperidine of the tungsten complex is hydrogen bonded to 17 through the carbonyl. The reaction of 1,2-h5-azaphosphetes with piperidine gives 17 which can be transformed to MO(CO)~ and W(CO)5 complexes noted above. Treatment of the triazaphosphinine to Schwart's reagent gives the metallacycle ClCp2hNH=PR2C(C02Me) C02Me). 65* 67

+

+

165p166

=e(

298

Organophosphorus Chemistry Pr'zN

\ /

NPr'2

Meo2Cf2 '0

Cyclvadition of 1,2-X5-azaphosphetes to MeNCS gives R2kNCRCPh= NC(S)NMe and to Me3SiNC0 to synthesis of the six-membered system, the saturated heterocycle Ph$N(CMe3)CH=CRCH=dR which upon treatment with methyl iodide followed by thermolysis and K2CO3 gives the desired material.16* Reactions of the chlorinated species Cl&=NC(NR2)=NC)(C1)=6H with diethylamine or morpholine occur at both the CCl and PCl sites.169The reaction of PC15 and dicyanomide gives Cll!=NC(Cl)=NC(N=PC13)=$J and the PCls/melamine reaction gives two modification of N3[C(N=PC13)]3.170 The 5+2 cyclo-addition of MeC02CI CC02Me with diazaposphinines gives the first seven-membered cycloiminophosphorane, 18 which is unstable to rearrangem e n t . " ~ ~Cationic ~~ species have also been explored. The reaction of Ph2PCH2CH2PPh2 with P h ( B r ) e N gives the dicationic entity, 19 or Ph&NC(Ph)NPPh2CH2eH2+Brl- is obtained.25 Relatively few contributions in cyclophospha(thia)zene chemistry have appeared in this period. The reduction of the sulfur-sulfur bond in the bicyclic entity 1,5-PbP2N4S2with M(BEt3H) gives M2PbP2N4S2(M=Li,Na,K). Treatment of the anion with CH212gives the CH2 bridged bicyclic, 20 (R=R'=H). Successive deprotonation and methyliodide treatment leads to 20(R=H,R'=Me) and 20(R=R'=Me). Treatment of Na2PbP2N4S2with (Cp*RhC12)2 gives 21. Reactions of M2PbP2N4S2with a variety of other elecrophiles, ICH2CH21, PhCHBr2, CHI3, CBr,, MeSiC12, Me2SnC12, PhPCl2, S2C12, CeC14, or FeBr2 regenerates the disulfide bond in 1,5-PbP2N4S2.173 The tellurium phosphazene derivative, Me3SiN=PPh2N=fe(Cl)N(SiMe3)PPh2=&SiMe3 when treated with RNHLi gives a tellurium dimide dimer R N T ~ ( V N R ~ ) ~ T(R=PPh2=NSiMe3) ~NR accompanied by Ph2P(=NSiMe3)NRSiMe3. 74 Thermal ring expansion reactions of

7: Phosphazenes

299

Clk(O)=NPC12=kPC12 gives the first macrocyclic cyclothionylphosphazenes. The twelve-membered species C1~(O)NPC1~NPC1~N~S(O)ClNPC1~NPC1~~ was obtained as a cis-trans mixture. The cis,trans,cis,trans isomer of the largest discrete inorganic heterocyclic, Cl~(O)N(PCl~N)~S(O)ClN(PlC~N)~S(O)ClN (PCl2N)S(0)ClNPCl2NPCl2k,yet structurally characterized was also isolated. NMR and FAB mas spectrometry of the crude reaction mixture shows the presence of [(NSOCl)(NPC12)2]x(x=2-6). 175 5

Metallocyclic Phosphazenes

Increased interest has been shown in systems wherein a metal (or metalloid) is part of a ring system containing at least one phosphazene unit. These ring systems may be formally covalent in nature or coordination compounds of phosphazene containing ligands. The use of phosphoranimines, R3PNSiR’3 and their anions, R3PNl-, as monodentate ligands was covered in Section 2. These ligands can also bridge metal centers leading to rings and cages. The reactions of MnX2(X=Cl,I) with Me3SiNPEt3 give [MnCl2(Me3SiNPEt3)I2and Mn12(Me3SiNPEt3). Thermal decomposition of the latter leads to I&nN(PEt3)SiMe2hPEt3 along with SiMe4.176The VCuMe3SiNPMe3 interaction gives VCb(Me3SiNPMe3) which adds a second mole of the ligand under thermolytic conditions to give [V3C16(NPMe3)5]C1.Hydrolysis gives [V3C16(NPMe3)5] [V@&l8(NPMe3)2]. In the cation both p3 and monodentate NPMe3- units are observed while in the anion p2 NPMe3- bridges exist.177Other reactions of R3SiNPR3proceed with initial silicon-nitrogen cleavage. For example, AsC13 plus Me3SiNPMe3 gives AsC1(NPMe3)l2Cl2. Addition of SbClS or SnCb leads to [AsCl(NP Me3)2SbC14]SbC16and [A~Cl(NPMe3)~snCbl. All three AsCl complexes have p2 NPMe3 ligands.17*The transition metal dihalides MX2 (MX=Mn; X=Cl, Br; Ni, X=C1) combine with neat Me3SiNPEt3 at elevated temperatures give the cubic clusters [MX(NPEt3)l4 with p3 NPEt3 l i g a n d ~ . ’Metal ~~ acetates such as CU~(O~CR (R=Me,Ph) )~ also react with Me3SiNPMe3 leading to C&(NP Me3)3(02CR)5along with Me3SiOC(O)R. The distorted C y tetrahedron has p3-NPMe3ligands. 8o Reactions of phosphoraminto complexes can be accomplished without disruption of the phosphazene ligand. Alkylation of [MnBr(NPEt& with butyllithium gives [Mn(n-Bu)NPEt3)]4.lS1 The monoden-

300

Organophosphorus Chemistry

N-

CI I Pd- CI

Me3S!

Et

SiMe3

Et

tate TiCl3NPPh3 species undergoes reductive exchange with benzyl bromide to provide [TriBr2(NPPh3)2]2which ultilizes 2-NPPh3 ligands. Lithium methoxide gives C12ti(NPPh3)OMeTi(NPPh3)C128Me. lS2 The combination of PdC12(NCPh)2 with 1,3,4-C,#3(N3)(CN)NPPh3 involves coordination of two of the ligand sites as shown in 22.62A variety of planar complexes are obtained from 1,3-diphosphazene arenes. Thus 1,3-C6H4~=PPh3)(N=PPh2CH2PPh2) adds [Rh(C0)2Cl]2 giving 1,3-C6IX$h=PPh2CH2PPh2dh(CO)Cl]N=PPh3. The symmetric ligand 1,3-C6H4(N=PPh,CH2PPh2)2 adds one and two moles of the rhodium precursor to give &H4N=PPh2CH2PPh2Rh(CO)(Cl)PPh2CH2Ph2P=h and C6&[(rjRh(CO)(Cl)PPh2CH2PPh2]2re~pectively.~~ The phosphoranimine nitrogen center can be one donor site in bidentate behavior in a variety of phosophoranimine complexes. The structure of L i ~ N C &exhibits a CPNLi ring which is favored by electrostatic forces. Retention of this ring in solution was established by NMR (6Li, 13C,15N,j1P)spectroscopy and MNDO calculations.183 Metallation of Py3P=NSiMe3 (Py=Zpyridinyl) with MeLi gives a five membered metallocycle with lithium coordinated to the imino and pyridinyl nitrogen atoms. The remaining two lithium coordination sites are occupied by 2,2'bipyridine. A slower reaction occurs with Ph3P=NSiMe3 and the product, 23, involves two phosphoranime ligands employing the imino nitrogen atom and the 2-aromaGc carbon center as coordination sites.ls4 The Staudinger reaction of Ph2PfiAlR2PPh2N(PPh2)AlR2fiPh2and Me3SiN3 gives PhzP&PPh2=N(SiMe3)A1R2 which upon treatment with Me3COK and Me3SiCl is transformed -to the open chain derivative Ph2PN(SiMe3)PPh2=NSiMe3. lS5 Complexes of the type (COD)FhPPh2RPPh,=& (M=Rh, Ir; R=CH2, CH2CH2,1,2-C&) can be obtained from [M(COD)C1]2 and Ph2PRPPh2= NSiMe3. Cationic species, [(COD)d4PPh2RPPh2=lbRt]+ arise when R'=p-C6F4CN, C&(N02)2 or C&I3(NO2)2. Iminophosphorano-phospholes can also function as bidentate ligands in metal c~mplexes.'~ The bis(iminophosphoranes) bridged by a saturated carbon moiety provide a range of interesting coordination chemistry. Deprotonation of the bridge followed by addition of M*&(PR3)2 (M=Pd, Pt; X=C1 Br; PR =PEt3, PMe2Ph) gives the fourmembered metallacycles R3P(X)MN(Ar)=PPh2 (R')PPh2=NAr. Heating of the complex leads to ortho metallation as observed in 24. The exocyclic phosphazene group can be protonated and the aza-Wittig reaction with C02 produces

*

301

7: Phosphazenes

+ 1-

(25)

(24)

R3P(X)hN(Ar)=PPh2k(R')P(0)Ph2.87 Direct reaction of the neutral ligand, CH2(PPh2=NAr)2, with Pt & PR gives the protonated fourmembered metallacycle p3P(X) tN(Ar)=PPh2 HPPhZNHAr]' via the openchain intermediate C12(R3P)PtN(Ar)+PPh2CH2PPh2=NAr.Products vary with ligand concentration such that a 2:l meta1:ligand ratio produces [R3P(Cl)$tN(Ar)=PPh2CH2PPh2=AAr]' which is transformed into the aforementioned four-membered rin A 1 2 meta1:ligand ratio produces the deprotonated species R3P(Cl) tN(Ar)=PPh2 HPPh2=NAr and HC(PPh2 NHAr)Z+Cl-. lS8 When CHMe(PPh3=NArh is used, the open-chain C12(R3P)PtNAr=PPh2CHMePPh2=NAr, is an intermediate on the way to ultimate formation of [R3P(C1)ptNAr=PPh2CHMePPh2=fiAr]+C1-.76 The (COD)&lNR=PPh2CHPPh2=NR,(M=Ir, Rh), species can undergo metal or ligand (nitrogen) centered reactions. Alkylating agents form N-alkyl derivatives while I2 produces 25. 189 The bis(phosph0ranimine) ligands bridged by nitrogen have been widely studied. Reaction of HN[P(NMe2)2NH]2with Ba[N(SiMe,)zlt leads via bridge deprotonation to the phosphoranimine complex BaNHP(N Me2)2NP(NMe21kH. Electrochemical studies of C13&NPPHh2NPPh2& (M=W, Mo) show two one electron reduction steps. The data confirm the strong donor ability of the ligand which stabilizes high oxidation states.lgl Oxidative chemistry is evident in the reaction of LiN(PPh2) with PtC12 in which 26 (M=Pt) is formed.The analogous reaction with FeC12 gives the reactive intermediate 26 (M=Fe) which can be stabilized by addition of two carbonyl moieties via addition of CO. Akylation of the platinium complex occurs at nitrogen atom of the fourmembered ring. If PtC1, is the starting material 26 (M=Pt) is still obtained.lg2 The reaction of Ph2PNHP(0)Ph2 with (C3H5)2Pd2C12 followed by deprotonation of the amine gives 27.193*194 The same general route involving initial phosphine coordination followed by amine deprotonation gives a variety of metallacycles with the same bidentate phosphorudoxygen coordination motif. These include ( C 0 D ) M m P h (M=Rh, IR), which can oxidatively add methyl iodide,194and M(OPPh2N Ph2)2 (M=Pt, {Pd).195The combination of anhydrous FeC13 and fPh2P(O)]2NH is a good route to Fk(OPPh2NPPh26)3.26 The

+%

$------E

+%

302

Organophosphorus Chemistry Php

N- P-

9

Pd- 0,

PhPP,

PPh;,

0-,Pd-

P- N Ph2

-(27)

same complex is obtained when Fe2(CO)9 reacts with (Ph2P)2NHin the presence of air.196 The same ligand (Tpip) has been used for a variety of lanthanide complexes: M(Tpip)3 (M=Pr,Dy), Pr(Tpip)3.L(L=H20, Me2C0, CH3CHClC02H), Pr2(Tpip)4(RC02)which are effective NMR shift reagents for carboxylic acids and their carb0xy1ates.l~~Solvent extraction of scandium, thulium and europium can be accomplished with the Tpip ligand.198Modifications of the ligands involving substitution of oxygen with heavier chalcogens have been ex lored. Thus metathesis of Ph TeC and K[(SPPh&N] gives Ph3Te(SPPh2NPPh2).199 The M&2) (M=Pd, Pt; E=S, Se) species have been prepared and characterized.200The symmetrical dithioimidodiphosphinates form Ni(1I) complexes. The derivative is planar while the corres ondin tetra henyl complex is tetrahedral.201 Mixed chalcogen derivatives R2Sn(SPPh2NPPh2 )2 (R=Me, Ph) are obtained from R2SnC12 and the potassium salt of the ligand.202The reaction of MX2 with [R2P(S)]2NHgive the structurally characterized h[SPPh2NPPh2$]2 (M=Pd, Pt) complexes.203 The potassium salt of the selenium analog, KPh2P(Se)l2N, provides a useful entry into a variety of complexes. Thus MC12(PR3)2 gives [&4(SePPh2N$e)(PR3)]+Cl- (M=Pt, Pd) along with a small quantity of the mixed ligand species [SkPPh2NPPh2Se]pd[SePPh2NPPh2],and Rh[SePPh2NPPhzSe]2 COD can be prepared.2" The isopropyl ZnCO3, CdC03 or NiC0303Ni(0H)~gives Cd,Ni) tetrahedral complexes.205The N(PPhzSe),- anion reacts with SnC12 to give two crystalline forms of SN[SePPh2NPPh2SeI2.The yellow form is rigorously planar while the red form has the tin(I1) atom above the plane of the four selenium donor centers.200The photolysis of Mp(SiMe3)2]2with Me3CP(E)NHR gives &l[EP(CMe3)2fi(R)]2 (M=Zn,Cd; R=ipr, C6H11;E=Se, Te).207

6

Poly@bosphazenes)

This section is concerned with polymers derived from open-chain phosphazenes, phospha(thia)zenes and related cross-linked materials. Cyclolinear and cyclomatrix materials as well as carbon-chain polymers with cyclophasphazene substituents are covered in Section 3. General and specific reviews have appeared including an overview of recent development in inorganic polymers including poly(phosphazenes),208a comprehensive survey of hybrid siloxane-phosphazene system^,*^*^ water-soluble phosphazenes and related hydro gel^,^^^-^^^ a brief survey of polymerization reactions and mechanisms,21 and sulfur containing poly(phosphazenes).2*

7: Phosphazenes

303

The synthesis of poly(phosphazenes) from small molecule precursors is an ongoing area of concern. Ring opening polymerization of N3P3C16in the presence of greater than two weight percent of AlC13 leads to quantitive formation of low molecular weight (NPC12)na213A mixture of AlC13 and Et2SnCl2 leads to high molecular weight (NPC12)nm214A new synthesis of poly(dich1orophosphazene) utilizes C13P=NSiMe3 and trace quantities of PC15. This ambient temperature process leads to modest molecular weights with narrow polydisparities. The use of C12(Ph)P=NSiMe3leads to P h C1 215 An elegant synthesis of poly@hospholazene), 28, starts with Br CH2CMe CMe Ha, prepared from PBr3 and 2,3butadiene, which is treated sequentially with LiN(SiMe3)2, C2C16 and LiOPh to give Me3SiN=fi(OPh)CHzCMe=CMecH. Themolyis of the spirophosphoranimine gives A variety of mixed trifluoethyoxy-phenoxy or methoxy phosphites, (R0)3-n(CF3CH20)nP,polymerize to low molecular weight poly(phos phazenes) in the Staudinger reaction with Me3SiN3. Kinetics and correlation to electronic structure have been explored.l6 Transformation of phosphoranimes to [(CF3CH20)2PN]n with low to modest polydispersity and molecular weight has been achieved using electrophilic initiators such as SbC15.217A patent for the same polymerization using Bu4NF and related species as the catalyst has been granted.218 Formation of poly(phosphazene) derivatives by replacement of chlorine atoms in (NPC12), is the traditional route to new phosphazene polymers. High yield syntheses of [NP(OC6H4R)& (R=Br,CN,COMe,COPh,N02) can be accomplished from the parent phenol and K2CO3 in THF.'13 An extensive series of polyalkylether phosphazenes, [NP(0R),ln [R=(CH2)20Me,(CH2 CH20)2R (R=Et,n-Bu,Me), CH2CH-(OMe)CH20Me,CH2CH[O(CH2CH2 O),M]CH20(CH2CH20),Me (x=l-3, y=1-3)], are available from the sodium salts of the parent alcohols (ROH). Aqueous solutions of the polymers are soluble below the lower critical solubility temperature (LCST) and precipitate above the LCST. Cross-linked films were also examined as hydrogels. The enthalpies of phase separation from water were determined by DSC and found to be related to the determined LCST.219 Mixed substituent 2-(2-methoxyethoxy)ethoxy and 4-(2-(2-methoxyethoxy)phenoxy) or 4-(4-(2-(2-methoxyethoxy)ethoxy)phenyl)phenoxy phosphazenes have been prepared with only certain combinations showing water solubility and LCST behavior.220 Nonlinear optical (NLO) polymers of the type [NP(RN(Me)C6&N0&(O(CH2CH20)2Me)2-x]n(X < 0.5); R=O(CH&, O(CH2)6, OCH2(2-pyrrolidino) and [NP(O(CH2)2N(Me)C6H4 C H = C H C ~ H ~ N O (O(CH2CH20)2Me)l-6], ~)O.~ have been prepared and examined by variable temperature solid state 31Pand 13CNMR spectroscopy. The 13Cdata

++t

304

Organophosphorus Chemistry

showed that a longer chain (R) lowered the temperature of quenching of side chain motion. The 31P data suggests coupling of side chain and backbone motions.221 The sodium salt route was employed to couple a series of phenols, iodo naphthol, as well as HOCH2CH20Ar where Arznaphthyl and biphenyl units with H,Br and I substituents to the poly(phosphazene) chain. High refractive indices, which can be tuned by the nature of the substituent, are observed.222High-temperature, forcing conditions are needed to overcome steric barriers in the synthesis of polyphosphazenes with fused-ring aryloxyl side groups such as 1- or 2-naphthyloxy, 1-naphthylmethoxy, 1-naphthylethoxy, 9-anthryloxy and 9-phenanthryloxy.' l4 Amino-organosiloxanes can be prepared from the [N-methylaminopropyl]siloxanes,NHMe(CH2)3(SiMe;?O),SiMe3 (n= 1,2). The polymers in question also contain trifluorethoxy, 2-(2-methoxyethoxy)ethoxy or p-methylphenoxy groups. Low glass transition temperatures ( - 83 to - 22 ") were obtained with the trisiloxanes giving the lower values.223*224 Hydrosilylation of organopoly(phosphazenes) with unsaturated side groups also gives siloxane substituted material^.^"-^^' The reactions of primary amines NH2R (R=Me, Et, n-Pr, allyl, n-Bu, n-Hex and Ph) with [NS0C1(NPCl2)dn give hydrolytically stable poly[(amino)thionylphosphazenes]. Mixed substituent (n-Bu, allyl) systems were also prepared. NMR and wide-angle X-ray scattering showed these systems to be atactic and amorphous.228 In addition to the hydrosilylation reactions noted above, other reactions of organofunctional units on the phosphazene chain have been utilized to produce new polymers. The reaction of amino containing substituents with 1,3-propane sulfone leads to alkylsulfonation of the parent polymer.229Deprotonation of (Ph(Me)PhN), with butyl lithium followed by reaction with fluorinated aldhydes and ketones gives a series of fluoroalkoxy derives [Me(Ph)PNlx[RFR C(OH)CH2(Ph)PNIy. Fluorination of [Me(Ph)PNlx[(Me2C(OH)CH2)P(Ph)NIY with Et2NSF3 leads to replacement of the hydroxyl function with a fluorine atom.230Sequential treatment of mP(OPh)l .7(OC6H4Br)0.3Inwith BuLi, PhzPCl and BuI gives a polymer bound Wittig reagent which gives the polymer bound phosphazene and olefin elimination upon treatment with benzophenone.121 Coordination of manganese carbonyls to FJP(OPh)2]1,[NP(OPh)OC6H4CN]y (y=0.06,0.28) gives polymeric complexes which show a very irreversible oxidation wave in cyclic voltametry experiments.13* Silver nitrate complexes of poly[bis(alkylamino)phosphazenes] have been prepared and their ionic conductivity examined.231A series of polyether glycol methyl ether phosphazenes and the corresponding lauryl ethers have been prepared and the conductivity of their lithium triflate complexes has been explored.232Related studies on (NP(OCH2 CH20CH2CH20MeX,[(OCH2)yCH3]2-y)n (x= 1, y=2-9) and the corresponding lithium triflate salts show a relationship between ionic conductivity and alkyl side chain length.233 Free radical grafting of maleic anhydride to [NP(OPh)2-x (OC6&Et),], and of allylphenoxy polyphosphazene to poly(viny1-alcohol) films has been noted.234The solution and solid state benzophenone sensitized photolysis of [NP(OC6H4CH2Ph)2]nleads to gel formation in the solid state but alternative behavior, dominated by follow up reactions, in solution.235Allylamino derivatives are cross-linked using E-beams to produce resist materials O

7: Phosphazenes

305

suitable for mi~rolithography.~~~ Benzophenone initiated photo cross-linking of ~P(OPh),(OC6H4Et)2-X]N has been utilized as a means to preparing membrane systems.237Reduction of the nitro group in [P(OPh)(OC6H4N02)N]~to the amine allows for reaction with maleic and phthalic anhydride to give phenylimide and maleimide derivatives. Polyimide thermoset resins can be grafted on to the phosphazene to give semi-interpenetrating networks with toughened high performance properties.238 Poly(organophosphazenes) with 2-butenoxy or 4-(ally1oxy)phenyl phenoxy and other substituents form interpenetrating networks with polystyrene, poly(methy1 methacrylate), poly(acrylonitrile), poly(acry1ic acid) and poly(dimethyl~iloxane).~~~ Phosphazenes with methylamino or 2-(2 methoxyethoxy)-ethoxy (MEEP) substituents were blended with a broad range of organic homopolymers. The degree of miscibilitiy was evaluated by DSC and transmission electron microscopy.239 A composite material of poly[bis(carboxylato)phosphazene] and hydroxyapatite was prepared from the phosphazene and CaHP04-2H20/Ca@04)20. Certain of the calcium ions cause cross-linking of the carboxylates in the phosphazene leaving calcium deficient hydroxyapatite. Phosphazene incorporation increases the thermal stability of the composite.240Nanocomposites of MEEP and cryptand [2.2.2] intercalated into sodium ion exchanged montmorillonite (a magnesium, aluminum silicate) show * 242 increased ionic conductivity over the parent sodium m~ntmorillonite.~~~ Poly(phosphazenes) as biomedical materials is an ongoing area of interest. Amino acid ester substituents allow for biodegradability of the poly(phosphazene) which in turn makes them of interest as matrices for slow release of bioactive agents. Partial substitution with phenylalanine ethyl ester and imidazole gives a system for controlled-release of naproxen. The anti-inflammatory behavior of the drug can be maintained for weeks, providing control of chronic situations.243 Controlled release of the narcotic antagonist naloxone from matrices of bis(ethy1glycinate) or mixed diethylglutamate and ethylglycinate phosphazenes has been examined.244Biocompatability and pharmacokinetic studies on the mixed substituent systems are a~ailable."~Chemotherapeutic agent release to adjacent solid tumors can also be accomplished by the biodegradable polymer approach.246 Systems with biodegradable moieties and groups which can be radiation cross-linked have been patented as delivery systems for drugs, diagnosing imaging agents, e t ~Low . ~molecular ~ ~ weight poly(phosphazenes) with amino acid ester side chains form complexes with diamine platinum(I1) ions which have been evaluated for antitumor activity."* A three dimensional matrix system derived from poly[(methylphenoxy)(ethyglycinato)phosphazene] was seeded with osteoblast cells. Cellular growth was detectable within a day suggesting the potential for use of the polymer as a bioerodible structure for skeletal tissue regeneration.24s31PNMR techniques for monitoring phosphazenes being prepared for polymeric matrix medical ligands have been presented.250Microspheres obtained by ionic cross-linking of poly(organophosphazenes) with polyelectrolyte substituents are a recent and exciting focal point for biomaterials. One recent application involves microparticles from poly(carboxylatophenoxy phosphazenes) with encapsulated contrast agents for medical imaging.2s1The carboxylatophenoxypolymer in solution shows immunoadjuvant

306

Organophosphorus Chemistry

activity. The ionically cross-linked microspheres induce high antibody serum concentration^.^^^ Poly(L-lysine) coated phosphazene microspheres have been proposed as oral vaccine delivery systems.253Mixed substituent polymers containing polyelectrolytes, e.g. carboxylic or sulfonic acids, or hydroxyl groups as well as biodegradable groups have been patented for delivery systems for vaccines for influenza and tetanus among others.254Microencapsulation materials which can be formed by photo cross-linking are available from poly(organophosphazenes) derivatives of 4-hydroxychalcone or (cinnomoyl chloride). Applications to encapsulation of bioactive materials and imaging agents are mentioned.255Airencapsulated microspheres for ultrasound imaging can be prepared phosphazene p~lyelectrolytes.~~~ A brief mention of polyphosphazene surgical sutures has appeared.257 The dividing line between synthesis, physicochemical characterization and applications of poly(phosphazenes) is often difficult to discern. Publications which focus more extensively on measurements are still a major component of the literature in this area. Computational studies include a study of the conformations of [NP(OPh),], using the rotational isomeric state model. Non-bonding interactions were calculated for rotational isomers and the results imply suppression of the torsional motion of the backbone.258Ab initio methods were applied to the structure of poly[(diphenoxy)thionylphosphazene] using short chain models. A highly polarized backbone with alternating bond lengths was indi~ a t e d 5N . ~ NMR ~ ~ data (from 31Pcorrelation spectroscopy) for [P(OPh)2N]o,94 [P(OP~)(OC~H~CN)N]O.O~ has been r e p ~ r t e dSurface .~ properties of poly(organ0phosphazenes) with dimethylsiloxane surfaces have been probed using XPS and contact angle measurement techniques. Surface enrichment in siloxanes was noted when phenoxy is a co-substituent but CF3 groups dominate when trifluoroethoxide is the c o - s ~ b s t i t u e n tAnomalies .~~~ in T I (spin lattice relaxation) and the tangent of dielectric have been related to residue chlorine atoms in poly(alkoxyphosphazenes).258 Thermomechanical properties and phase behaviors continue to be a focal point of phosphazene characterization. The pressure dependence of phase transitions in NP(OCH2CF3)2], (PTFE) was studied by dilatometry. Increased pressure results in an increase in the transition temperature from the crystalline to mesomorphic state, an increase in the temperature range of the mesomorphic state and structural reorganization under pressure.259p260DSC, X-ray and dynamic mechanical studies on poly(fluoroa1koxyphosphazenes) show a tendency to formation of columnar mesophase and condis crystal structures.261p262 Phosphazene random and block copolymers prepared by anionic polymerization of phosphoranimines have been studied by DSC and variable temperature wide-angle X-ray scattering variables relating to the thermal transitions were established. The degree of crystallinity and microphase separation were also probed.263 Morphological studies show that methoxyethoxyl trifluoroethoxy block co-polymers differ from random co-polymers of equivalent composition. All the block species undergo a mesophase transition. Morphological and structural (unit cell) characteristics resemble those of PTFE. Square and globular shapes are obtained from dilute solutions while chain extension occurs in the melt crystallized materials.264 DSC studies of (PPh2N)o.76(P(Ph)(o-

7: Phosphazenes

3 07

tolyl)N)0.24 show a single T, and subsequent mesophase transition. A complex array of forms can be obtained by various heatingkooling Dielectric thermal and dynamic mechanical analysis of poly(phosphazenes) provides information on mechanical dispersion and glass transition behaviors.266TGA studies of [NP(NHCH2Py)x(OPh)y]n(Py=pyridyl) show depolymerization to trimers and tetramers if x -c 50% and insoluble residue formation if x > Dilute aqueous solution characterization of [NP(OC6H4C02H)2]nby GPC with multiangle light scattering detection allowed for Mark-Houwink coefficient determination. Problems with universal calibration using non-charged PEO standards occur due to ion exclusion interference with size exclusion.267 Poly(phosphazene) solid electrolytes for batteries still attracts attention, most of it being in the patent literature for this period. New forms of vanadium oxide have been considered for cathodic materials and their effect on the microstructure of the phosphazene or phosphazene/PEO blends examined by impedance spectroscopy and other techniques. Octafluoropentoxyphosphazenes has been employed as the e l e c t r ~ l y t and e ~ ~thermal ~ ~ ~ ~as~ well as conductivity properties of the lithium triflates examined.270MEEP/amorphous V205 with lithium salts form a system where the polymer is concentrated on or near the oxide surface.271 More complex mixtures of phosphazenes and a copolymer of three or more organic monomers have been Structure integrity of the phosphazene electrolyte may be enhanced by cross-linking and a benzophenone photo initiated W approach using alkyl CH moieties is available.273Interpenetrating polymer networks of the phosphazene electrolyte and a polymer which is electrochemically stable have been prepared.274MEEP and related oligo(eth1eneoxy)polyphosphazenes are the most widely used phosphazene electrolytes. Ethyleneoxy units terminated with allylic units have been ~ r e p a r e d and ~ ~ ~c .r o~ ~~s - l i n k e d . ~ ~ ~ Oligooxyethylene derivatives suppress dendrite g r o ~ t h and ~ ~the~ batteries * ~ ~ ~ have long cycle lives.277*278.279 The added salt is preferably LiBF4.279The chlorophosphazenes have also been examined for inertness to the conductor constituents.280 Poly(phosphazenes) have become widely studied as membrane materials. Deprotonation of [P(Ph)MeN], followed by reactions with chlorosilanes gives a broad range of polymers with = PCH2SiMe2R [R=Me,(CH2)2Me,(CH2)2CF3, (CH2)2(CF2)8F]substituents. In addition to NMR and DSC, gas permeability measurements were carried out. The silyl group increased the permeability (but not selectivity) to a value of about 8.9 for C 0 2 relative to CH4.281The oxygen gas permeability of a variety of phenoxy, alkoxy and amino phosphazenes was examined with the poly(di-n-hexylamino)(n-hexylamino) derivative having the highest values. Mechanical properties are improved by the addition of crosslinking.282Detailed studies of cross-linking of the poly(n-butylamino)(diallylamino)phosphazene derivative have been reported as has the oxygen gas permeab i l i t ~ It . ~ has ~ ~ been shown that phosphazene membranes coupled with the ChromatoChem process are capable of removing metal ions and chlorinated hydrocarbons from process streams. Designs of industrial demonstration units and basic physicochemical characterization studies are presented.284In an interesting study of [NP(OPh),], and several carboxylated derivatives, separation of 2689269

Organophosphorus Chemistry

308

tritiated water from aqueous solution of up to 43% could be attained.285 Aryloxyphosphazenes with grafted oligopolysiloxameswhich are transformed to cross-linked films allow for extraction of n-butano1286and ethylacetate226 from water by pervaporation. Membranes of PTFE have been studied for separation of methanol and ethanol from water.287 Miscellaneous applications of poly(ph0sphazenes) include ter-butoxycarbonyl protected materials for chemically amplified resists in microlithography,288thin film electroluminescent devices,289optical wave guides,290aryloxy derivatives as components of fire-, heat- and impact-resistant materials29'and components of a low-density, thermoplastic elastomeric, ablative insulation for rocket motors.292

7

Crystal Structures of Phosphazenesand Related Compounds.

The following compounds have been examined by diffraction methods. All distances are in picometers and angles in degrees. Compound

Cornrnents

Ref:

PN LPNC

160.5(3) 124.3(2)

3

Ph3PNMe2+BF4-

PN L PNC

162.7(4), 162.4(4) 122.7(3), 118.3(2)

3

Mes* N=P-N=P(NMe2)3

no details given

ArNHP(=NAr)Br2 Ar=2,4,6-(CMe3)3C6H2

No PN data

P(NH&+Cl-

PN

Av. 160.7(2)

P(NH2)4+1-

PN

160.7(2)

[(NH2)3PN(NH2)31Cl

ORTEP only

11

PhC(NPPh2Sipr)2+Br-

no details given

25

ClC(N=PC13)2+SbC16-

ORTEP only cidcis conf.

170

ORTEP only monoclinic and triclinic forms

170

PN 153.5(2), 169.3(3), 172.3(2) L NPN 108.3(2)

185

Ph2PN(SiMe3)PPh2=NSiMe3

P=N P(1I)N L PNP

155.6(2) 167.7(2) 130.0(1)

5

293 10,11

11

26

309

7: Phosphazenes

29

P=N P-N

151.0(4) 164.4(2)

33

[Me3SiNP(ipr)2CMe2Li]2

PN dimer

158.7(2)

60

[Ph3PNPPh3]+[SPh2PNPPh2SJ-

cation L PNP 143.0(5) PN 157.7(3) anion L PNP 180 PN 154.4(2)

294

61 62 295

(Me3P=NSiMe3ZrC13)20*(CH2C12) 1.33

1,3-C&(N=PPh2CH2PPh2)2

PN

1,3-C&(N=PPh2CH2PPh&N=PPh3)

PN

[Me3SnSPPh2NPPh2S],

158.1(3) 156.9(4)

63

158.5(4) 157.8(2) Trigonal biyramidal trans-S2SnC3 PN 157.2(5) 160.5(5) LPNP 133.4(2)

63

PN L SNP

162.1 122.3

65

PN L SNP PN LSNP

159.5(3)-161.1(2) 118.1(2)-122.3(2) 160.8(3) 119.2

70

PN 157.8(7)-161.7(2) L SeNP 116.8(4)-122.7(4)

70

PN L SNP

159.7(5)-161.9(5) 123.5(3)-127.1(3)

64

70

71

Organophosphorus Chemistry

310

(Me3Si)NPMe3*IC1

N . . .IC1 PN 161.1(7) f PNSi 136.5(5)

73

Ph3PNeIC1

N . . .IC1 PN 162.3(6) f PNCl 113.5(4) f PNI 126.0(3)

73

[M e3P=NH]+IC12-

N -H-IC12 PN 165.6(5), 166.1(6) f PNP 134.4(4)

73

PN

74

152.4(3)

p-F dimer PN 157.2(4) PN(H) 157.6(5) f TiNP 174.3(3) f TiN(H)P 133.5(3)

74

Planar Cr PN 158.6(3) f CrNP 119.87(13)

75

Planar Pd PN 159.8(3) f PdNP 118.41(14)

75

[CuC12(Me3SiNPMe3)]2

Planar Cr, p-C1 PN 159.7(3) L CuNP 119.8(2)

75

(Et3P=NSiMe3)2Mn12

PN 160.7(3) f MnNP 118.0(7) PN 155.9(3) 155.3(3) f CPN 106.57(15) 105.22(15)

CHMe(PPh2=NC6H4Me)2

176 76

Preliminary data linear MoPN

81

PN 159.9(5) f AuNP 115.9(3), 133.9(3)

82

[P~~PN(AuPP~~)~]+BF~-.THF~CH~C~~ PN 162(1)

82

L PNAu 118.0(5)-123.5(5)

2,2-N3P3Cb(N=P(OPh)&

PN,,d, PN,,

161.6(5), 159.6(5) 160.6(7)

92

311

7: Phosphazenes

P=Nexo 153.3(5), 151.6(5) L NPN (substituted) 111.6(3)

2,2-N3P3(OPh)4[N=P(OPh)3]2

PNendo 159.1(13), 162.1(13) PNexo 162.1(13), 160.6( 15) P=N,, 162.1(13), 160.6( 15) P-N,,, 153.0( 19, 152.7( 15) L NPN (substituted) 114.0(6)

92

N3P3(0Ph)gN=P(OPh)3

PNendo 159.6(5) P=Nexo 152.5, 152.0(5)

92

N3P3(NHPr)5N=P(NHPr)3.HCI

PNendoAV. 158.9 P=N,, 157.2(8)

92

[PN(OC6H4C6H40&H2n+ 1)2]

confirms mesophase; mol. length of mesophase

98

(E+)2P3N3F5NPF2NPF2NPFs2l-

PNendo 152.9( 10)-161.5( 10) PN,, 152.0(11)- 169.4(9)

101

E=(Me2N)3S (Me2N)3S+(NPF2)3NPF3

102 Eight membered ring with one PF3 center PN adjacent to PF3 160.6(2), 160.8(2) PN 152.3(2)-155.6(2)

twelve membered ring with one PF3 center PN adjacent to PF3 159.5(10),

102

160.8( 10)

PN others 149.3(10)-156.3(9) PN

N3P3L6 L= 1-naphthoxy

156.1-156.8; 156.3

104

slightly twisted PNendo 156.5(3)-158.6(3) P, 162.7(4)

296

ansa (2,4) bridge PN 157.7-162.9 L NPN 112.0-120.4 L PNP 116.9-122.0

106

reassigned space group PN 155.3(3), 154.5(3)

297

redetermination slightly puckered PN 156.8-157.9 Av.L PNP 121.5(2) Av.L NPN 117.1(1)

114

Organophosphorus Chemistry

312

N3P3L6 L=Znaphthoxy

N4P4L3 L= 1-naphthoxy

N4P4L8 Lz2-naphthoxy

planar PN 155.5-159.3(4) Av.LPNP 122.7(2) Av.LNPN 117.3(2)

114

planar Av. PN 157.9 L NPN 116.6(2)-119.0(2) L PNP 120.3(2)-121.4(2)

114

planar PN L NPN L PNP

114 156.0(8)-161.3(9) 114.9-119.3(4) 121.4-124.5(5)

boat 153.2(8)- 156.5(6) PN Av. LNPN 120.4(3) Av. L PNP 134.3(5) slightly puckered boat 153.7(6)-15 5.3(6) PN Av. 1NPN J23,3(3) Av. LPNP144.5(4)

114

114

nearly planar PN 155.7(2)-159.9(2) L NPN substituted 114.63(10)

119

nearly planar PN 154.1(3)-159.1(3) L NPN substituted 115.9(2)

119

planar PN 154.7(3)-160.5(3) L NPN substituted 113.64(13)

119

non-planar PN 154.3(9)-159.1(9) L NPN substituted 115.9(5)

114

313

7: Phosphazenes

PN 155.6(3)-157.5(3) L NPN substituted 116.1(2)

114

PN 154.7(4)-158.6(4) 114 L NPN substituted 116.8(2), 116.3(2) PN 153.3(4)-159.0(4) L NPN substituted 115.5(2)

114

PN 155.8(2)-157.5(2) L NPN sustituted 115.95(11)

114

PN 157.2(3)-158.5(3) L NPN substituted 115.9(2)-117.7(2)

114

Chair 131 PNendo 165.1(3)-167.4(3) PNexO, equatorial 162.4(4)-163.7(4) PN,,, axial 163.8(3)-165.2(3) almost planar 132 Av. PN 158.3(4), 155.4(5), 1 5 6 310) L NPN 115.8(2), 119.3(3). 119.7(3) cation: PNendo 155.0(2)-170.2(2) PN,, 160.0(2), 159.0(2) anion: PN 156.7(2)-157.6(2) L PNP 135.8(1)

133

16.CuC12*PdBr R=Me;R’=dimethylpyraolyl

non-planar PNendo 156.3(11)-160.4(11)

134

16.C0C12.0. 5CHzC12 R=Me;R‘=Ph

PNendo 154.8-162.1(4) PN,,(mean) 168.7(4) L PN(Co)P 1 18.64(21) L PNP 121.25(22), 122.74(23)

135

slightly puckered PN 156.7(3)-158.0(3) L NPN 117.8(1)-119.3(1) L PNP 120.7(2)-121.6(2) L OPO 98.0(1)-98.6(1)

137

slightly puckered PN 157.2(2)-157.7(3) L NPN 117.7(2) L PNP 122.6(2) 99.7(1) LOP0

137

ORTEP only

117

Organophosphorus Chemistry

314 (Pri2N)2P=N

H

C02Me

C02Me

(32)

L= 1,4-bridgedbi-Znaphthol L’=2’,4‘-bridged O(CH2)20(CH2)20(CH2)20 2,2’,4,6-N3P3(L)(L) ORTEP only L=2,4-bridged bi-2-naphthol L=2’,-bridged O(CH&O(CH2)20(CH2)20 1

117

R2P=NCH(Ph)=N R=N(CHMe2)2

PNendo 167.0(4), 167.5(4) PN,, 162.5(4), 164.43) L NPN endo 86.0

166

R2P=N(BH3)CH(Ph)=k(BH3) R=N(CHMe2)2

PNendo 169.4(2), 168.9(2) PN,, 160.8(20, 161.3(2) L NPN endo 79.8(1)

166

R&=NCH(Ph)=NCH(Ph)=A R=N(CHMe2)2

PNendo 163.0(2) PN,,, 164.4(2) LNPN 110.1(1)

166

(32)2PdC12

trans 32 units coord. to Pd through encocyclic N PNendo 172.5(3) PN,,, 162.0(3), 161.8(3)

167

17*M0(CO)4L L=piperdine

17 coordinated to Mo through endocyclic N PNendo 166.4(3) PN,, 162.3(3) 162.8(3)

167

17*W(C0)5L L=piperdine

17 H-bonded to L through endocyclic carbonyl PNendo 16 1.3(4) PN,, 163.5(5), 164.5(4)

167

C12+=NC(C1)=NC(N=PC13)=N

ORTEP only

170

18

PNendo 159.7(3) PNbridge 167*8(3)

21

PN L NPN

158.7(5)-165.2(5) 120.3(2), 116.6(3)

173

RN=TkN(R’)Te(=NR)&(R’) R=t-Oct, R-NPPh2NSiMe3

PN 153.0(4)-164.2(4) LTeNP 113.4(2), 111.1(2)

174

i

171,172

315

7: Phosphazenes

[S(O)Cl=NPC12=NPC12N]4

cis, trans, cis, trans isomer PN 152.6(17)-163.2(17)

175

[(Et3P=NSiMe3)ClMnC1]2

p-C1 bridged dimer PN 159.7(5), 160.7(4) L MnNP 118.6(1), 119.5(1)

176

Me&N( =PEts)MnIzh( =PEt3)

PN

176

156.8(7)-157.8(6)

[V3Clb(NPMe3)5]2V404C18(NPMe3)2=6MeCN cation: p3-NPMe3 177 PN 159(2)-164(2) Anion: p2-NPMe3 PN 161(2) pz-NPMe3dimer PN 162.7(7)-164.7

178

p2-NPMe3dimer PN 162.8(13)-162.9(13)

178

p2-NPMe3dimer PN 162.1(3)-162.2(3)

178

p3-NPMe3cube PN 158.9(3), 158.6(3)

179

p3-NPMe3cube PN 159.3(7), 160:8(7

179

p3-Cu4distorted Td PN 158.9(3)-160.0(3)

180

p3-NPMe3cube PN 156.9(5)

181

p3-NPPh3 Dimer PN 161.0(3)

182

pz-OMe dimer PN 158.1(6)

82

PN L CPN

161.4(4) 105.6(3)

83

Me$iN=P(Me)Py.Li(bipy) Py=2-pyridyl; bipy=bipydridyl

PN

163.4(3)

84

23

PN

156.2(2), 156.2(3)

Ph2PNPPh2=N(SiMe3)AlMe2

PN

[Mn(n-Bu)NPEt&

[TiC12(0Me)NPPh3]

160.07(14), 162.48(13) 170.06( 14) LNPN 97.89(7)

184 186

Organophosphorus Chemistry

316 Ph2PnPPh2 I II OC-Rh-N I CI

Ph2Pn

PPh2 I

yJN-::-co II

I

(33)

Ph2MeP(Cl)$tNAr=PPh2C(H)MePPh2=FkAr PN

161.1(5), 161.8(6)

76

PN

155.5(4), 161.2(4)

187

Ar =C6H4-p-Me 24 X=Cl, R=Et, Ar=C6H4-p-Me

[Et3P(C1)btCH(PPh2=NAr)PPh2=NAr]+Pt(PEt3)C13Ar=C6H4-p-Me

PNendo 160.4(7) PN,, 163.4(6)

188

PhMe2b(C1)PtCH(PPh=NAr=PPh2=fiArjCCI Ar=CsH4-p-Me

PNlendo PNeY.0

33

PN 161(1

25

PN PN

61.3(6) 63.4(6)

188 63

56(2)-161(2)

189

159.4(7)-164.6(8)

192

trans Fe(C0)2 PN 158.3(3)-164.4(3)

192

[Me26]+11M=Pt

methyl N in four membered ring PN 159.5(12)-170.0(9)

192

Fk(O=PPh2N=PPh2b)3*CH2C12

PN L PNP

157.8(6)-160.2(7) 123.0(4)-124.9(4)

26,196

27

PN L PNP

158.2(4), 162.5(4) 126.5(3)

193

Ph2 (MeO)P(C1)P;loPPh,NPh2.CH2Cl2PN L PNP

161.0(9), 161.4(9) 115.32(53)

194

C O D ( M e ) w P h 2

PN L PNP

159.5(7), 162.1(7) 118.21(4)

194

P-Ph&

PN LPNP

157.7(8)-164.1(8) 115.3(5), 115.4(5)

195

M(TPiP13 M=Pr, Dy Tpip=OPh2NPPH201-

No PN data

197

317

7: Phosphazenes

No PN data

197

No PN data

197

PN L PNP

159.4(9), 158.0(9) 137.6(6)

199

PN L PNP

163.5(6), 158.4(7) 123.3(4)

200

planar PN L PNP

159.9(l), 160.0(2) 120.4(1)

PN L PNP

159.9(3), 157.8(3) 132.0(2)

202

PN LPNP

159.3(7), 158.1(7) 134.1(4)

202

Ph(SPR2NPR ~ $ 2 R=ipr

PN 159.8(4), 158.8(4) PdS2P2N ring dist. boat

203

Pk(SPR2NPR2$)2 R=ipr

PN 158.6(4), 157.5(4) S2P2Nfragment planar with Pt out of plane

203

Zh(SPR2NPR&

PN L PNP

158.1(2) 140.5(3)

205

CCI(SPR~NPR~S)~ R=ipr

PN L PNP

157.3(3)-159.2(3) 141.0(2), 143.2(2)

205

di(SPR2NPR2$2 R=ipr

PN LPNP

158.1(2) 137.1(2)

205

Ph2PNmdSePPh2NPPh2ke

PN

158.1(11)-163.6(9)

204

&I(S~PP~~NPP~~S~)~ yellow form

planar LPNP 136.2(13) different Se-Sn dist.

206

i n (SePPh2NPPh2Se)2 red form

pyramidal L PNP 129.3(10)

206

Zh(SePR2NR)2

PN 161.1(3), 161.4(3) L NPSe 102.39(13), 102.69(13)

207

prl3flPiP)3L Tpip=OPPh2NPPh201L=H20, Me2CO,CH3CHC1CO2H pr2(Tpip)4L2 Tpip=OPPh2NPPHzOlL=Citronellate, hydroxybutyrate

R=ipr

R=ipr; R=CMe3

201

318

Organophosphorus Chemistry

[(CF3CH20)2PN],[(CH30CH2CH20)(CF3CH20)PN], cell dimensions

264

265

References 1.

2. 3. 4. 5.

6. 7. 8.

9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27.

Phosphorus, Sulfur, Silicon Relat. Elem., 1996,109-110. Phosphorus, Sulfur, Silicon Relat. Elem., 1996, 111. W. K. Holley, G. E. Ryschkewitsch, A. E. Koziol and G. J. Palenik, Inorg. Chim. Acta, 1995,239, 171. F. Lopez-Ortiz, E. Pelaez-Arango and P. Gomez-Elipe, J. Magn. Reson. A , 1996, 119,247. M. I. Povolotskii, A. B. Rozhenko, V. V. Poloviko and A. N. Chernega, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 109-110, 617. Z. R. Gulyaeva, I. I. Patsanovsky, E. A. Ishmaeva, L.Stefaniak and W. Domalewski, Phosphorus, Sulfur Silicon Relat. Elem., 1996,111,27. E. D. Raczynska, P.-C. Maria, J.-F. Gal and M. Decouzon, J. Phys. Org. Chem., 1994,7,725. T. M. Shcherbina, A. P. Laretina, V. A. Gilyarov and M. I. Kabachnik, Russ. Chem. Bull. (Engl. Transl.), 1994,43,641. Z . Moldovan, S. Nicoara, M. Culea, 0. Cozar, I. Fenesan, P. Vegh and J. J. Rios, J. Mol. Struct., 1995,348, 393. S. Horstmann and W.Schnick, 2. Naturforsch. B: Chem. Sci., 1996,51, 127. W. Schnick, S. Horstmann and M. Haser, Phosphorus, Sulfur Silicon Relat. Elem., 1996,109-110,93. M. Saady, L. Lebeau and C. Misoskowski, Tetrahedron Lett., 1995,36,4237. M. Saady, A. Valleix, L. Lebeau and C. Misoskowski, J. Org. Chem., 1995, 60, 3685. D. E. Shalev, S. M. Chiacchiera, A. E. Radkowsky and E. M. Kosower, J. Org. Chem., 1996,61,1689. P. Molina, C. Lopez-Leonardo, J. Llamas-Botia, C. Foes-Foces and C. FernandezCastano, J. Chem. SOC.,Chem. Commun., 1995,1387. M. L. White and K. Matyjaszewski, J. Polym. Sci., Part A: Polym. Chem., 1996 34, 277. N. K. Eldin, Phosphorus, Surfur Silicon Relat. Elem., 1995,102,25. V. A. Nikolaev, G. P. Kantin and P. Yu. Utkin, Russ. J. Org. Chem. (Engl. Trans.)., 1994,30,1354. R. U. Amanov, E. L. Matrosov, Yu. M. Antipin, A. A. Khodak, A.G Matveeva, Yu. M. Polikarpov, Kh. T. Sharpiov, Yu. Struchkov and M. I. Kabachnik, Russ. Chem. Bull. (Engl. Transl.), 1993,42,77. C. A. Obafemi, Phosphorus, Sulfur Silicon Relat. Elem., 1995,104, 1. R. W. Fischer and M. H. Caruthers, Tetrahedron Lett., 1995,36,6807. A.-M. Caminade and J. P. Majoral, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 111,61. F. Plenat, H. J. Cristau and K. El Aarj, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 111,32. J. B. Hendrickson, T. J. Sommer and M. Singer, Synthesis, 1995, 1496. G. Alcaraz, V. Piiquet, A. Baceiredo, F. Dahan, W. W. Schoeller and G. Bertrand, J. Am. Chem. SOC.,1996,118,1060. J. Ellermann, P. Gabold, F. A. Koch, M. Moll, A. Schmidt and M. Schultz, ZNaturforsch, B: Chem. SOC.,1996,51,201. R. M. Kamalov, N. A. Khailova, V. A. Al’fosov and M. A. Pudvoik, Russ. J. Gen. Chem. (Engl. Transl)., 1995,65,37.

7: Phosphazenes

28. 29. 30. 31.

32. 33.

34. 35.

36. 37.

38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60.

319

C. M. Angelov, D. A. Mazzuca and R. G. Cavell, Phosphorus, Suljiur Silicon Relat. Elem., 1996,109-110,541. R. G. Cavell, C. M. Angelov and D.. A. Mazzuca, Phosphorus, Suljiur Silicon Relat. Elem., 1996,109-110, 625. N. V. Lukashev, A. D. Averin, P. E. Zhichkin, M. A. Kazawkova and I. P. Beletskaya, Phosphorus, Suljiir Silicon Relat. Elem., 1996, 109-110, 609. A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova and I. P. Beletskaya, Russ. J. Org. Chem. (Engl. Transl.), 1995,31, 367. A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova and I. P. Beletskaya, Russ. J. Org. Chem. (Engl. Transl.), 1995,31,452. A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova and I. P. Beletskaya, Russ. J. Org. Chem. (Engl. Transl.), 1995,31, 445. A. D. Averin, N. V. Lukashev, A. A. Borisenko, M. A. Kazankova and I. P. Beletskaya, Russ. J. Org. Chem. (Engl. Transl.), 1995,31,363. A. Ya. Dorfman, R. R. Abreimova, D. N. Akbaeva and S. M. Aibasova, Russ. J. Gen. Chem. (Engl. TransT), 1995,65,890. M. Fialon, M. R. Mazierez, Y. Madaule, C. Payrastre, M. Sanchez, J. G. Wolf, A. 0. Fadima and V. D. Romanenko, Phosphorus, Suljiir Silicon Relat.Elem., 1995, 102,243. L. Jager, N.Inquimbart, M. Taillefer and H.-J. Cristau, Phosphorus, Surfur Relat. Elem., 1996, 111, 124. A. Zwierzak and K. Osowaska-Pacewicker, Phosphorus, Suljiur Silicon Relat. Elem., 1996,109-110, 569. J. M. Alvarez-Gutierrez and F. Lopez-Ortiz, Tetrahedron Lett., 1996,37,2841. M. Jayaraman, V. Sirirajan, A. R.A. S. Deshmukh and B. M. Bhawal, Tetrahedron, 1996,952,3741. S. Eguchi, K. Yamashita, Y. Matsushita and A. Kakehi, J. Org. Chem., 1995, 60, 4006. H. Poschenneder and H.-D. Stachel, J. Heterocycl. Chem., 1995,32, 1457. M. M. Ismail, M. Abdel-Megid and H. M. El-Shaaer, Indian J. Heterocycl. Chem., 1995,5,59 (Chem. Abstr., 1996,124, 176013). P. Molina, A. Pastor and M. J. Vilaplana, Tetrahedron Lett., 1995,36, 8283. F. Palacios, D. Aparicio and J. M. de 10s Santos, Tetrahedron, 1996,952,4837. M. Nitta, Y.Iino, S. Mori and T. Takayasu, J. Chem. Soc., Perkin Trans. I , 1995, 1001. T. Okawa and S. Eguchi, Tetrahedron Lett., 1996,37 8 1 . L. Lebeau, C. Mioskowski and M. Saady, PCT Int. Appl., W09600733 (Chem. Abst., 1996,124,289881). B. Eisswein and M. Moeller, Angew. Chem., Int. Ed. Engl. 1996,35, 623. W. Memeger Jr., US Pat., US 5399662 (Chem. Abstr., 1995,123,84389). S . Kuehlung and J. Stebani, Eur. Pat., Appl., EP 685503 (Chem. Abstr., 1996, 124, 147 1 57). A. Solladie-Cavallo, D. Roche, J. Fischer and A. DeCian, J. Org. Chem., 1996, 61, 2690. W. D. McGhee, M. D. Paster, D. P. Riley, K. W. Ruettimann, A. J. Solodar and T. E. Waldman, PCTInt. Appl., WO 9518098 (Chem, Abstr., 1995,123,287146). A. Molenberg and M. Moeller, Macromol. Rapid Commun., 1995,16,449. M. Fisher, Eur. Pat. Appl., EP 691334 (Chem. Abstr., 1996,124,264005). R. Hager, 0. Schneider and J. Schuster, Eur. Pat. Appl., EP 626415 (Chem. Abstr., 1995,123,10862). S. Rubinsztajn, Get. Offen., DE 4423924 (Chem. Abstr., 1995,123, 114998). H. Schickmann, R. Lehnert, H.-D. Wendt, H.-G. Srebny and R. Holger, Ger. Offen, DE 434464 (Chem. Abstr., 1995,123,229276). R. Hager, B. Deubzer and 0. Schneider, Eur. Pat., Appl., EP 626414 (Chem. Abstr., 1995,123, 10277). J. S. Razzano, Ger. Offen., DE 19530214 (Chem. Abstr., 1996,124,264028).

320

Organophosphorus Chemistry

61.

J. S. Razzano, D. P. Thompson, P. P. Anderson and S. Rubisztajn, Ger. Offen., DE 4424001 (Chem. Abstr. 1995,123,84946). J. S . Razzano, US Pat. Appl., US 5457220, (Chem. Abstr., 1995,123,341406). R . Hager, R. Braun, 0. Schneider and B. Deubzer, Ger. Offen., DE 4422813 (Chem. Abstr. 1996, 124, 147166). A. Muller, B. Neumiiller and K. Dehnicke, Chem. Ber., 1996,129,253. T. Chivers, M. Parvez and M. A. Seay, 2. Anorg. Allg. Chem., 1995,621,1813. R. S . Pandurangi, K. V. Katti, R. R.Kuntz, C. L. Barnes and W. A. Volkert, Inorg. Chem., 1996,35,3716. J. Lin, R. McDonald and R. G. Cavell, Orgunometallics, 1996, 15, 1033. K. C. Molloy , M. F. Mahon, I. Haiduc and C. Silvestru, Polyhedron, 1995, 14, 1169. H. Folkerts, W. Hiller, M. Herker, S. F. Vyboischehikov, G. Frenking and K. Dehnicke, Angew. Chem. Int. Ed. Engl., 1995,34, 1362. F. Kunkel, H. Folkerts, S. Wocadlo, H.-C. Kang, W. Massa and K. Dehnicke, Z. Naturforsch. B: Chem. Sci., 1995,50, 1455. H. Folkerts, S. Wocadlo, W. Massa and K. Dehnicke., 2. Anorg, Allg. Chem., 1996, 622, 863. I. Fenesan, A. Hantz, M. Culea, S. Nicoara and M. Bogdan, Phosphorus, Sulfur Silicon Relat. Elem., 1996,111, 192. J. Grebe, K. Harms, F. Weller and K. Dehnicke, 2,Anorg. Allg. Chem., 1995, 621, 1489. M. Grun, K. Harms, R. Meyer zu Kocker, K. Dehnicke and H. Goesmann, 2. Anorg. Allg. Chem., 1996, 622, 1091. T. Miekisch, H. J. Mai, R. Meyer zu Kocker, K. Dehnicke, J. Magull and H. Goesmann, Z. Anorg. Allg. Chem., 1996,622,583. M. W. Avis, C. J. Elsevier, N. Veldman, H. Kooijman and A. L. Spek, Inorg. Chem., 1996,35,1518. R. G. Cavell and M. D. Mikoluk, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 111, 150. G. Schick, A. Loew, M. Nieger and E. Niecke, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 111,29. J.-P. Majoral, A. I. Gau, M. Zablocka, A. Mattieu, N. Cenac and M. K. Pietrusiewicz, Phosphorus, Surfur Silicon Relat. Elem., 1996,109-110, 185. J. C. Kim, B. M. Lee and J. I. Shin, Polyhedron, 1995,14,2145. C. E. Laplaza, W. M. Davis and C . C. C u m i n s , Angew. Chem., Int. Ed. Engl., 1995,34,2042. A. Bauer, F. Gabbai, A. Schier and H. Schmidbaur, Philos. Trans. R SOC.London, Ser. A , 1996,354,381. A. H. Amrallah, A. E. Arifien, R. M. Awadallah and S . M. Sirry, Bull. Fac. Sci., Assiut. Univ., B. 1995,24,73. N. Kajiwara, T. Nakanaga, T. Takefumi, J. Tada and T. Kameshima, Jpn. Kokai Tokyo Koho, JP07048526 (Chem. Abstr., 1995,123,231482). T. Banno, M. Umeno, S. Mitsusada and E. Kimura, Jpn Kokai Tokyo Koho, JP 07090201 (Chem. Abstr., 1995,123,289858). C. W. Allen, Trench Polym. Sci., 1994,2, 342. H. R.Allcock and S. E. Kuharcik, J. Znorg. Orgunomet. Polym. 1995,5,307. H. R.Allcock and S. E. Kuharcik, J. Znorg. Organomet. Polym. 1996,6,1. R. E. Tapscott, S. R. Saggs and D. Dierdorf, ACS. Sym. Ser., 1995, 611, (Halon Replacements), 151. M. E. Amato, K. B. Lipkowitz, G. M. Lombarado and G. C. Pappalardo, J. Mol. Struct., 1995,372,69. H. Dolhaine, R. Fuhler, G. Hagele and W . Klaui, Z. Nuturforsch, B: Chem. Sci., 1995,50,1665. H. R. Allcock, S. E. Kuharcik, K.. Visscher and D. C. Ngo, J. Chem. SOC.,Dalton Trans., 1995,2785.

62. 63.

64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92.

7: Phosphazenes

93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125.

321

F. Lopez-Ortiz and E. Pelaez-Arango, Bull. Magn. Reson. 1995,!37,206. S . Paasch, B. Thomas and K.Kruger, Phosphorus, Sulfur Silicon, Relat. Elem., 1996, 111, 14. K. Moriya, H. Mizusaki, M. Kato, S. Yano and M. Kajiwara, Liq. Cryst., 1995, 18, 795. K. Moriya, S. Nakagawa, S. Yano and AM. Kajiwara, Liq. Cryst., 1995,18,919. K. Moriyz, T. Suzuki, S. Yano and M. Kajiwara, Liq. Cryst., 1995, 19,711. A. M. Levelut and K. Moriya, Liq. Cryst., 1996,20, 119. A. J. Jaglowski, K. M. Gabriel and M. S. Prpi, Rept. No. Am-TR-223; Order No. AD-A273674 (Chem. Abst., 1995,123,343420). C. Combes, F. Plenat and H.-J. Cristau, Phosphorus, Suljiur Silicon Relat. Elem., 1995,111,33. E. Lork, P. G. Watson and R. Mews, J. Chem. Soc., Chem Commun., 1995,1717. E. Lork, D. Goehler and R . Mews, Angew. Chem., Int. Ed. Engl., 1996,34,2696. C. W. Allen, R. F. Hayes, C. N. Myer, A. S. Freund and M. E. Kearney, Phosphorus, Surfur Silicon Relat. Elem., 1996,109-110,79. F. Forohar, P. R. Dave, T. Axenrod, C. D. Bedford, R. Gilardi and C. George, Phosphorus, Surfur Silicon Relat. Elem., 1995, 101, 161. E. S.Sumar, M. G. Muralidhara and V.Chandrasekhar, Polyhedron, 1995,14,1571. F. Crasnier, M.-C. Labarre, F. Sournies, C. Vidal and J.-F. Labarre, J. Mol. Struct., 1996,380,157. L. Margerum, B. Campion, J. D. Fellman and M. Garrity, WO 9528966 (Chem. Abstr., 1996,124,202320). J.-F. Labarre, F. Sournies, F. Crasnier, M.-C. Labarre, C. Vidal, J.-P. Faucher and M. Graffeul, Phosphorus, Sulj;r Silicon Relat. Elem., 1996,109-110, 525. A. A. Afon’kin, A. E. Shumeiko and A. F. Popov, Russ. Chem. Bull. (Engl. Transl.), 1995,44,2006. L. L. Nikogosyan, A. A. Pogosyan, V. A. Ovasapyan, M. G. Indzhikyan and R. 0. Matevosyan, Izobreteniya, 1995,273 (Chem. Abst., 1996,124,343679). L. Corda, G.Delogu, A.Ma&oni, E.Ma&oni and G. Podda, Gazz. Chim. Ital., 1995,125,491. S . Anzai and S. Juta, Jpn. Kokai Tokyo Koho, JP07101819 (Chem. Abst., 1995, 123, 65902). G. A. Carriedo, L. Fernandez-Catuxo, F. J. Garcia Alonso, P. Gomez-Elipe, P. A. Gonzalez and G. Sanchez, J. Appl. Polym. sci., 1996,59, 1879. H. R.Allcock, S. Al-Shali, D. C.Ngo, K. B. Visscher and M. Parvez, J. Chem. Soc., Dalton Trans. 1995, 3521. D. Kumar and A. D. Gupta, Macromolecules, 1995,28,6323. K. Brandt, I. Porwolik, T. Kupka, A. Olejnik, R. A. Shaw and D. B. Davies, J. Org. Chem., 1995,60,7433. K. Brandt, I. Powolik, A. Olejnik, R. A. Shaw, D. B. Davies, M. B. Hursthouse and G. D. Sykara, J. Am. Chem. Soc., 1996,118,4496. K. Brandt, I. Porwolik, K. Placha, T. Kupka, A. Olejnik, R. A. Shaw and D. B. Davies, Phosphorus, Sulfur Silicon Relat. Elem. 1996,111, 30. A. Vij, S. J. Geib, R. L. Kirchmeier, J. M. Shreeve, Inorg. Chem., 1996,35,2915. R. Kraemer, C. Galliot, J. Mitjaville, A.-M. Caminade and J. P. Majoral, Heteroat. Chem., 1996,7,149. S.-K. Kwon and C.-L. Jun, Kongop Hwahak, 1994,5, 843 (Chem. Abst., 1995, 123, 341028). G. N. Kurov, N. A. Nedolya and B. A. Trofimov, Russ. J. Org. Chem. (Engl. Transl.), 1995,31, 134. G. Bosscher and J. C. van de Grampel, J. Inorg. Organomet. Polym.,1995,5,209. G. Bosscher, H. Hager, A. Meeztsma, A. P. Jekel and J. C. van de Grampel, Phosphorus, Su@u Silicon, Relat. Elem. 1996,109-110,67. K. Inoue, K. Takiue and T. Tanigaki, J. Polym. Sci., Part A: Polym. Chem., 1996, 34,1331.

322

OrganophosphorusChemistry

126.

129. 130.

T. Y. Jang, H. J. Ji and M. J. Han, Nonmwnjio-Sekye Hanminchok Kwahak Kisulcha Jonghap Haksul Taehoc: Kobunja Chaelyo, Hwtakong Punkwa, 1993, 1124 (Chem. Abst., 1995, 123, 112891). J. Y. Chang, H. J. Ji and M. J. Han, Bull. Korean Chem.Soc., 19915,16,674 (Chem. Abst., 1995,123, 170279) Y. W. Chen-Yang, H. F. Lee, S. F. Chen, C. Y. Li and Y. S.Chin, Phosphorus, Surfur Silicon Relat. Elem., 1996, 109-110, 75. I. Dez and R. DeJaeger, J. Inorg. Organomet. Poly., 1996,6, 11 1. I. Dez, L. Pemberto and R. DeJaeger, Phosphorus, Surfur Silicon Relat. Elem., 1996,

131. 132. 133.

A. Steiner and D. S. Wright, Angew. Chem.. Int. Ed. Engl., 1996,35,636. H . R.Allcock, D.. Brennan and R. R. Whittle, Heteroat. Chem. 1996,7,67. M.Alberti, A. Marecek, Z. Zah and P. Pastera, 2. Anorg,. Allg. Chem., 1995, 621,

134. 135.

K. R.J. Thomas, V. Chandrasekhar, C. D. Bryan and A. W. Cordes, J. Coord Chem., 1995,35,337. K. R.J. Thomas, V. Chandrasekhar, S. R. Scott and A. W. Cordes, Polyhedron,

136.

U. Diefenbach and M. Kretschmann, Phosphorus, Surfur Silicon Relat. Elem., 1996,

137.

G. A. Carriedo, P. Gomez-Elipe, F. J. Garcia Alonso, L. Fernandez-Catuxo, M. R. Diaz and S. Garcia Granda, J. Organomet. Chem., 1995,498,207. G. A. Carriedo, L. Fernandez-Catuxo, F. J. Garcia Alonso and P. Gomez-Elipe, J. Organometal. Chem., 1995,503, 59. L. Ya. Medvedeva and I. A. Rozanov, Rurs. J. Coord. Chem.(Engl. Transl.) 1995, 21,442 (Chem. Abst., 1995,123,131 132). T. Itaya, Y. Sasaki, T. Tanigaki, A. Matsumoto and K. Inoue, Chem. Lett., 1996,

127. 128.

111, 34.

1771.

1195,14,1607. 111,28. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151.

305. B. S. Nader, K. K. Kar, T. A. Morgan, C. E. Pawloski and W. L. Dilling, Tribol. Trans., 1995,35,37. B. M. Dekoven and G. E. Mitchell, ACS Symp. Ser. 1992,485, 15. B. S. Nader, 1993, US Pat., US 5 194652. E. E. Graham, US Pat, US 5493886 (Chem. Abst., 1996,124,265418).

M. Yang, F. E. Talke, D. J. Perettie, T. A. Morgan and K. K.Karr, IEEE Trans. Magn., 1994,30,4143. M. Yang, F. E. Talke. Tribol. Trans, 1995,38,636. S.-H. Choa, K. C. Ludema, G. E. Potter, B. M. DeKovon, T. A. Morgan and K. K. Karr, Tribol. Trans., 1995,38, 757. V.Sharma, M. Yang and F. E. Talke, Proc. SPIE-Int. Opt.Eng., 1996, 2604, 228 (Chem. Abst., 1996, 124,206643). S. Suzuki, F. Ebisawa and S. Ito, Jpn. Kokai Tokyo Koho, JP 07246630 (Chem. Abst., 1996,124, 10639). R. Kitajima, H. Sakurai and 0. Ito, Jpn. Kokai Tokyo Koho, JP 07089247 (Chem. Abst., 1995, 123, 183545). H. Ogawa and T. Kuryama, Jpn. Kokai Tokyo Koho, JP 07294893 (Chem. Abst., 1996,124,216259).

152. 153. 154. 155. 156.

A. Nagata, S. Nomura and T. Oosugi, Jpn. Kokai Tokyo Koho, JP 07331049 (Chem. Abst. 1996,124,319748). K . Tanitsu, H. Tanaka and T. Nakayama, Jpn. Kokai Tokyo Koho, JP 07102214 (Chem. Abst., 1995,123,289895). T. Sekya, Y. Nishioka Y. Okabe and Y. Okada, Jpn. Kokai Tokyo Koho, JP 071790658 (Chem. Abst., 1995,123,325813). M. Tani, M. Sasaki, S. Myahara and T. Ito, Jpn. Kokai Tokyo Koho, JP 07082482 (Chem. Abst., 1995,123, 171914). K. Mrata, S. Ichimura and S. Mogi, Jpn. Kokai Tokyo Koho, JP 06247989 (Chem. Abst., 1995,123, 113199).

7: Phosphazenes

157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187.

323

R. Lehnert, H. Kroening, H.Roesler, H. Schickmann, H. Rantschek and H.-D. Wendt, Ger. Offen., DE 4323 188 (Chem. Abst. 1995,123, 10279). H. Schickmann, H.-D. Wendt and R. Lehnert, Ger. Offen., DE4323184 (Chem. Abst., 1995, 123, 34410). D. P. Thompson, P. P. Anderson and D. Slick, Gen. Offen., DE 44241 15 (Chem. Abst., 1995, 123, 84970). R. Lehnert, H. Kroening, H. Roesler, H. Schickmann, H. Rautschek and H.-D. Wendt, Ger. Offen., DE 4323186 (Chem. Abst., 1995,123,10278). G . G. Frenkel, A. M. Shchetinin and 2. G. Oprits, Khim. Volokna, 1994,26 (Chem. Abst., 1996,124, 10777). M. Yoshizaki, Jpn. Kokai Tokyo Koho, JP 07188592 (Chem. Abst., 1995, 123, 231543). T. V. Vasileva, L. A. Orlova, F. A. Levites, N. A. Tolpekina, L. A. Chernykh, 0. A. Kiseleva, A. A. Volodin, A. S. Maksimov and E. A. Chernyshev, Zzobreteniya, 1993, 62 (Chem. Abst., 1995,123,86369). H. Matsuoka, S. Okita and M. Ishikawa, Jpn. Kokai Tokyo Koho, JP 07216235 (Chem. Abst., 1995,123,342217). R. Reau, A. Baceiredo and G. Bertrand, Phosphorus, Suljiur Silicon Relat. Elem., 1996,109-110,429. G. Alcaraz, A. Baceiredo, M. Nieger, W. W. Schoeller and G. Bertrand, Inorg. Chem., 1996,35,2458. K. Bieger, G. Bouhadir, R. Reau, F. Dahan and G. Bertrand, J. Am. Chem. SOC., 1996,118,1038. A. Foucaud and C. Bedel, Tetrahedron, 1995,51,9625. M. Yu. Dmitrichenko, V. G. Rozinov and V. I. Donskikh, Russ. J. Gen. Chem. (Engl. Transl.), 1995,65, 374. F. Belaj, Phosphorus, Suljiur Silicon Relat. Elem., 1996,109-110,71. J. Barluenga, M. Tomas, K. Bieger, S. Garcia-Granda and R. Santiago-Garcia, Angew. Chem. Znt. Ed. Engl., 1996,35,896. K. Bieger, M. Tomas, J. Barluenga, R. Santiago and S. Garcia-Granda, Phosphorus, Surfur Silicon Relat. Elem., 1996, 111,203. T. Chivers, M. Edwards, X. Gao, R. W. Hilts, M. Parvez and R. Volmerhaus, Inorg. Chem., 1995,34,5037. T. Chivers, X. Gao and M. Parvez, Inorg. Chem., 1996,35,9. Y.Ni, A. J. Lough, A. L. Rheingold and I. Manners, Angew. Chem. Int. Ed. Engl., 1995,34,998. H. J. Mai, S. Wocadlo, W. Massa, F. Weller and K. Dehnicke, 2. Naturforsch., B: Chem. Sci., 1995,50, 1215. T. Ruebenstahl, K. Dehnicke and J. Magull, 2. Anorg. Allg. Chem., 1995, 621, 1218. R. Garbe, S. Wocadlo, H.-C. Massa, K. Harns and K. Dehnicke, Chem. Ber., 1996, 129, 109. H.-J. Mai, H.-C. Kang, S. Wacadlo, W.Massa and K. Dehnicke, Z. Anorg. Allg. Chem., 1995,621, 1963. R. Meyer zu Kocker, J. Pebler, C. Friebel, K. Dehnicke and D. Fenshe, 2. Anorg. Allg. Chem., 1995,621, 1311. H.-J. Mai, B. Neumuller and K. Dehnicke, 2. Nuturforsch., B: Chem. Sci., 1996,51, 433. J.-S. Li, F. Weller, F. Schmock and K. Dehnicke, 2. Anorg. Allg. Chem., 1995,621, 2097. F. Lopez-Ortiz, E. Pelaez-Arango, B. Tejerina, E. Perez-Carreno and S. GarciaGranda, J. Am. Chem. SOC.,1995,117,9972. A. Steiner and D. Stalke, Angew.Chem., Znt. Ed. Engl., 1995,34, 1752. P. Braunstein, R. Hasselbring and D. Stalke, New. J. Chem., 1996,20,337. D. J. Law, G. Bigam and R. G. Cavell, Can. J. Chem., 1995,73,635. M. W. Avis, C. J. Elsevier, J. M. Emsting, K. Vrieze, N. Veldman, A. L. Spek, K. V. Kattesch and C. L. Barnes, Organometallics, 1996,15,2376.

324 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218.

Organophosphorus Chemistry M. W. Avis, K. Vrieze, H. Kooijman, N. Veldman, A. L. Spek and C. J. Elsevier, Znorg. Chem., 1995,34,4092. P. Imhoff, J. H. Guelpen, K. Vrieze, W. J.J. Smeets, A. L. Spek and C. J. Elsevier, Znorg. Chim. Acta, 1995,235,77. S . K. Pandey, Main Group Met. Chem., 1994,17,737. K. H. Moock, S . A. Macgregor, G. A. Heath, S. Derric and R. T. Boere, J. Chem. Soc., Dalton Trans., 1996,2067. J. Ellermann, P. Gabold, C. Schelle, F. A. Knoch, M. Moll and W. Bauer, 2.Anorg. Allg. Chem., 1995,621, 1832. M. B. Smith, A. M. Slawin and J. D. Woollins, Polyhedron, 1996,15,1579. A. M.Z. Slawin, M. B. Smith and J. D. Woollins, J. Chem. Soc., Dalton Trans., 1996, 1283. P. Bhattacharyya, A. M.Z. Slawin, M. B. Smith and J. D. Woollins, Znorg. Chem., 1996,35,3675. C. S . Browning, D. H. Farrar and D. C. Frankel, Inorg. Chim. Acta.,1996,241,111. N. Platzer, H. Rudler, C. Alvarez, L. Bakaoui, B. Denise, N. Goasdoue, ,M.-N. Rager, J. Vaissermann and J. C. Daran, Bull. Chem. Soc. Fr., 1995, 132,95. P. Sladek, 0. Navratil, M. Nouaman, A. Gronwald and E. Herrmann, Solvent Extr. Res. Dev. Jpn., 1995,2, 1 (Chem. Abst., 1995, 123,209986). A. Silvestru, I. Haiduc, R. A. Toscano and H. J. Breunig, Polyhedron, 1995, 14, 2047. P. Bhattacharyya, A. M.Z. Alexandra, D. J. Williams and J. D. Woollins, J. Chem. Soc., Dalton Trans., 1995,3189. R. Roesler, CSlvestru, G. Espinosa-Perez, I. Haiduc and R. Cea-Olivares, Znorg. Chim. Acta, 1996,241,47. R. Roesler, J. E. Drake, C. Silvestru, J. Yang and I. Haiduc, J. Chem. SOC.,Dalton Trans., 1996,391. D. Cupertino, R. W. Keyte, A. M.Z. Slawin, D. J. Williams and J. D. Woollins, Phosphorus, Su!f”r Silicon Relat. Elem., 1996,109-110, 193. P. Battacharyya, A. M.Z Slawin, D. J. Williams and J. D. Woollins, J. Chem. Soc., Dalton Trans., 1995,2489, D. Cupertino, R. Keyte, A. M.Z. Slawin, D. J. Williams and J. D. Woollins, Inorg. Chem., 1996,35,2695. R. Cea-Olivares, J. Novosad, J. D. Woollins, A. M.Z. Slawin, V. Garcia- Montalvo, R. Espinesa-Perez and P. Garcia y Garcia, J. Chem. Soc., Chem. Commun., 1996,519. M. Bochmann, G. C. Bwembya, M. B. Hursthouse and S . J. Coles, J. Chem. Soc., Dalton Trans., 1995,2813. I. Manners, Annu Rep. Prog. Chem., Sect. A: Inorg. Chem., 1195,91, 131. H. R. Allcock, Polym. Mater. Sci. Eng., 1993, 69, 98 (Chem. Abst., 1996, 124, 290947.) H. R. Allcock, Adv. Chem. Ser., 1996,248,l. S . E. Mallakpour and J. Asghari, Iran. J. Polym. Sci. Technol. (Persian Ed.), 1994, 7,210 (Chem. Abst., 1995,123,228940). D. Foucher, R. Rulkens, Y.Ni, A. Lough and I. Manners, Polym. Mater. Sci Eng., 1994,71,338 (Chem. Abst., 1995,123,286756). Y. S . Sohn, Y. H. Cho, H. Baek and 0.4. Jung, Macromolecules, 1995,28,7566. Y. Cho, H. Baek, 0.4%Jung, M.-J. Jun and Y. S . Sohn, Bull, Korean Chem. SOC., 1996,17,85 (Chem. Abst., 1996,124,147039). C. H. Honeyman, 1. Manners, C. T.Morrissey and H. R. Allcock, J. Am. Chem. Soc., 1995,117,7035. J. A. Gruneich and P. Wislan-Neilson, Polym. Prepr. (Am. Chem. Soc.. Div. Polym. Chem.), 1996,37(1), 61 1. R. A. Montague, J. B. Green and K. Matyjaszewski, J. Macromol, Sci., Pure Appl. Chem., 1995, A32,1497. R. A. Montague and K. Matyjaszewski, US Pat., US 5382644 (Chem. Abst., 1995, 123,33874).

7: Phosphazenes 219. 220. 221. 222, 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250.

325

H. R. Allcock and G. K. Dudley, Macromolecule, 1996,29,13 13. Y. B. Kim, C.-h. Cho and S. Y. Hong, Pollimo, 1996, 20, 163 (Chem. Abst., 1996, 124,290458). H. R. Allcock. C. G. Cameron, T. W. Skloss, S. Taylor-Meyers and J. F. Haw, Macromolecules, 1996,29,233. M. A. Olshavsky and H. R. Allcock, Macromolecules 1995,28,6188. H. R. Allcock, S. E. Kuharcik and C. J. Nelson, Macromolecules, 1996,29,3686. S. E. Kuharick, D. E. Smith, C. J. Nelson, H. R. Allcock and J. J. Fitzgerald, Polym. Mater. Sci Eng., 1994,71, 542. H. R. Allcock and D. E. Smith, Chem. Mater., 1995,7, 1469. A. Bac, D. Roizard, P. Lochon and J. Ghanbaja, Macromol. Symp., 1996,102,225. H. R. Allcock, K. B. Visscher and Y.-B. Kim,Macromolecules, 1996,29,2721. Y. Ni, P. Park, M. Liang, J. Massey, C. Waddling and I. Manners, Macromolecules, 1996,29,3401. E. H. Kingenberg, H. R. Allcock and M. F. Welker, Polym Mater. Sci. Eng., 1993, 69,353. P. Wisian-Neilson,G.-F. Xu and T. Wang, Macromolecules, 1995,28,8657. Y. W. Chen-Yang, J. J. Hwang and J. Y . Kau, Polym. Mater. Sci. Eng., 1994,71, 727. H. R. Allcock, S. E. Kuharcik, C. S. Reed and M. E. Napierala, Macromolecules, 1996,29,3384. H. R. Allcock, M. E. Napierala, C. G. Cameron and S. J. O’Connor, Macromolecules, 1996,29, 1951. L. Pemberton, R. DeJaeger and L. Gengembre, Phosphorus, Surfur Silicon Related Elem., 1996, 111,35. M. Gleria, F. Minto, L. Fambri and A. Pegoretti, Eur. Polym. J., 1995, 31,791. G. L. Grune, R. W. Greer, R. T. Chern and V. T. Stannett, Rad Tech Asia ’93 UVI EB con$, Expo., Proc.,, 1993,396 (Chem. Abst. 1995,123,212848). R. Wy&k, P. N. Pintauro, W. Wang and S. O’Connor, J. Appl. Poly. Sci., 1996,59, 1607. 0. L. Abu-Shanab, M. Duygulu and M. D. Soucek, Polym: Prepr. (Am. Chem. SOC., Div. Polym. Chem.), 1995,36(2), 231. H. R. Allcock and K. B. Visscher, US Pat., U. S . 5457160 (Chem. Abst. 1996, 124, 31250). C. S. Reed, K. S. Tenltuisen, P. W. Brown and H. R. Allcock, Chem, Mater., 1996, 8,440. J.C Hutchison, R. Bissessur and D. F. Shriver, ACS Symp. Ser., 1996,622,262. J.C Hutchison, R. Bissessur and D. F. Shriver, Polym. Mater. Sci. Eng., 1995, 73, 167. P. Caliceti, S. Lora, F. Marsilio and F. M. Veronese, Farmaco, 1995,50,867 (Chem. Abst., 1996,124, 185422). J.-A. Park, S.-J. Lee A.-K. Kim and K. S. Kim, Yakche Hakhoechi, 1995, 25, 109 (Chem. Abst., 1995,123,265945). M. R. Moon, J. A. Park, S.-J. Lee, H.-K. Kim and K.-S. Kim, Yakche Hakhoechi 1995,25,117 (Chem. Abst., 1995,123,265946). H . Brem, R. J. Langer and A. J. Domb, PCT Int. Appl., WO 9603984 (Chem. Abst., 1996,352704). H. R. Allcock, S. R. Pucher and K. B. Visscher, PCT Int. Appl., WO 95232736 (Chem. Abst., 1996,124,170022). H. Baik, 0. S. Jung, Y. K. Sung and Y. S. Sohn,Bull. Korean Chem. SOC.,1995, 16, 1074 (Chem. Abst., 1996,124,118 193). C. T. Laurencin, S. F. El-Amin, S. E. Ibim, D. A. Willoughby, M.Attwaia, H. R. Allcock and A. A. Ambrosio, J. Biomed. Muter. Res. 1996, 30, 133 (Chem. Abst., 1996,124,15591 1). A. Sulkowska and W. Sulkowski, Spectrosc. Biol. Mol., Eur. Conf., 6th, 1995, 523 (Chem. Abst., 1996,124,97693).

326

Organophosphorus Chemistry

251.

S. Cohen, A. K. Andrianov, M. Wheatley, H. R. Allcock and R. S. Langer, PCT Int. Appl., WO 9519184 (Chem. Abst., 1995,123,208874). L. G. Payne, S. A. Jenkins, A. Andrianov and B. E. Roberts, Pharm. Biotechnol., 1995,6,473 (Chem. Abst., 1996,124,126965). L. G. Payne, S. A. Jenkins, A. Andrianov, R. Langer and B. E. Roberts, Adv. Exp. Med. Biol. 1995,37lB, 1475 (Chem. Abst., 1996,124,97350). A. K. Andrianov, S. A. Jenkins, L. G. Payne and B. E. Roberts., US Pat., US 549673 (Chem. Abst., 1996,124,258503). H. R. Allcock, C. G. Cameron and D. E. Smith, PCT Int. Appl., WO 9528150 (Chem. Abst. 1996,124,89025). S . Cohen, A. K. Andrianov, M. Wheatley, H. R. Allcock and R. S. Langer, US Par. Appl. US 5487390 (Chem. Abst. 1996,124,337365). D. R. Tur, V. G. Kulichikhin, V. T. Palchun and A. S. Lapchenko, Izobretenyia, 1995,127, (Chem. Abst. 1996,124,299023). W. Sulkowski,A. Sulkowska and V. Kireev, Phosphorus, Surfur Silicon Relat. Elem., 1996, 111, 31. V. E. Dreval, E. I. Frenkin, D. R. Tur and V. G. Kulichikhin, Vysokomol. Soedin., Ser. A. Ser. B., 1995,37,248 (Chem. Abst. 1995, 123, 170794). E. Frenkin, V. Dreval and V. Kulichikhin, Polym. Mater. Sci., Eng., 1995,72, 353. N. A. Plate and E. M. Antipov, Macromol. Symp., 1993,98, 341. N. Plate, B. Shklyarule, S. Kuptosov, A. Zadorin and E. Antipov. Macromol. Symp., 1996,104,33. M . L. White, R. A. Montague, K. Matyjaszewski and T. Pakula, Polymer, 1995, 36, 3493. M. Kojima, J. H. Magill, M. L. White and K. Matyjaszewski, Macromol. Chem. Phys., 1995,196,1713. M . Kojima, J. H. Magill, U. Franz, M. L. White and K. Matyjaszewski, Macromol. Chem. Phys. 1995,196,1739. C. A. Williams and T. C. Ward, Adhes. SOC.,Proc. Sixteenth Annu. Meet. Int. Symp. Interphuse, 1993,77 (Chem. Abdst., 1995,123, 113362). A. K. Andrianov and M. P. LeGolvan, J. Appl. Polym. Sci., 1996,60,2289. J. L. Acosta, E. Morales, M. Paleo and J. R. Jurado, Eur. Polym. ., 1996,32,13. J. L. Acosta, E. Morales and J. R. Jurado, J. Appl. Polym. Sci., 1996,59, 1 1 73. J. L. Acosta and E. Morales, J. Appl. Polym. Sci., 1996,60, 1185. T. Maejima, K. Hironaka and T. Hayakawa, Jpn. Kokai Tokkyo Koho, JP 07192763 (Chem. Abst., 1995,123,233369). M. Yamazaki, Y.1 Shoji, S. Yoshimura, K. Nishio and T. Saito, Jpn. Kokai Tokkyo Koho, JP 07320782 (Chem. Abst., 1996,124,207221 .) H. R. Allcock, C. J. Nelson and W. D. Coggio, US Put., US 5414025 (Chem. Abst., 1995,123,61305). F. Eschbach, US Pat., US 5426005 (Chem. Abst.,, 1995,123,88497). J. Tada, T. Nakanaga, T. Kameshha and A. Inubushi, Jpn. Kokai Tokkyo Koho, JP 06236770 (Chem. Abst. 1995,123 13713). J. Tada. T. Kameshima and T. Nakanaga, Jpn. Koai Tokkyo Koho, JP 070226022 (Chem. Abst., 1995,123, 10285). A. Komaki, T. Hayakawa, K. Hironaka, K, Higashimoto, K. Nakai, T. Nakanaga, A. Inubushi and M. Sasaoka, Jpn. Kokai Tokkyo, JP 07105976 (Chem. Abst.. 1995 123,88383). K . Higashimoto, K. Hironaka, K. Nakai, T. Hayakawa, A. Komaki, M. Sasaoka, T.Nakanaga, A. Inubushi, N Watanabe and Y. Tei, Jpn. Kokai Tokkyo Koho, JP 07240233 (Chem. Abst., 1996,124,12376). T. Maejima, K. Hironaka, T. Hayakawa, A. Komaki, T. Nakanaga, A. Inubushi and M. Sasaoka, Jpn. Kokai Tokkyo Koho, JP 07161379 (Chem. Abst., 1995, 123, 204394). M. Maly-Schreiber and J. Michel, Ger. Offen. DE 4420095 (Chem. Abst., 1996, 124, 12349).

252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. 276. 277. 278. 279. 280.

7: Phosphazenes

281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297.

327

P. Wisian-Neilson and G.-F. Zu, Macromolecules, 1996,29,3457. M. Kajiwara, Adv. Sci. Technol., 1995,4,293 (Chem. Abst., 1996 124,344872). M. Kajiwara and T. Kimura, Proc. Int. Conf: Compos. Muter. Energy, 1995, 26 (Chem. Abst., 1996,124, 119365). E. S. Peterson, K. R. Arehart, D. C. Kunerth, M. L. Stone and R. F. Hammen, Sep. Processes Propc. Symp. 1995,27 (Chem. Abst., 1995,123, 16829). D. A. Nelson, J. B. Duncan, G. A. Jensen and S. D. Burton, J Membr. Sci., 1996, 112, 105. D. Roizard, R. Clement, P. Lochon, J. Kerres and G. Eigenberer, J. Membr. Sci., 1996,113 151. T . Uragami and T. Morikawa, Angew. Makromol. Chem., 1996,234,39. S. K . Yang, C. E. Park, J. H. Kang ad K. D. Ahn, Pollimo, 1994, 18, 622 (Chem. Abst., 1996,124, 18243). J. Ito, M. Sugiura and H. Sato, Jpn. Kokai Tokkyo Koho, JP 06200244 (Chem. Abst., 1995,123,44026). T . Noguchi, K. Naito, T. Saito, R. Sakurai and M. Ishiharada, Ger. Offen. DE 4446324 (Chem. Abst., 1995,123,127138). A. Watanabe, M. Higano and Y. Myata, Jpn. Kokai Tokkyo Koho, JP 07292233 (Chem. Abst. 1996,124,119131). D. E. Guillot, U,S Pat., US 5498649 (Chem, Abst., 1996,124,292034). M. Nieger, A. Ruban and A. Niecke, 2. Kristallogr., 1995,210,789. I . Haiduc, R. Cea-Olivares, S. Hernandez-Ortega and C. Silvestru, Polyhedron, 1995, 14,2041. T. Ruebenstahl, F. Weller and K. Dehnicke, Z. Kristallogr., 1995,210, 385. U . Diefenbach, H. R. Allcock and K. B. Visscher, Acta Crystallogr., Sect. C: Cryst. Struct. Commun., 1995, C51,1215. H. R. Allcock, S. Al-Shali, D. C. Ngo, K. B. Visscher and M. Parvez, J. Chem. Sue., Dalton Trans., 1996,2393.

8 Physical Methods BY R. N. SLINN AND J. C.TEBBY

While section 1 contains theoretical studies of general interest, studies relating to specific physical methods will be found in the appropriate section as in earlier volumes. The main techniques are again reviewed in the relevant section and the chromatography section expanded to include newer techniques such as GC-MS, ion chromatography and capillary electrophoresis (CE). Compounds in each subsection are usually dealt with in the order of increasing coordination number of phosphorus. In the formulae, the letter R normally represents hydrogen, alkyl or aryl, while X represents an electronegative substituent, Ch represents a chalcogenide (usually oxygen or sulfur) and Y and Z are used to represent groups of a more varied nature. The terminology apical and radial has been retained for the stereochemical description of substituents on five-coordinate phosphorus atoms that possess trigonal bipyramidal or octahedral geometry, so that the terms axial and equatorial can be reserved to describe the conformational preferences of substituents on four-coordinate atoms of any element in sixmembered and related rings.

1

Theoretical Studies

1.1 Studies Based on Molecular Orbital Theory. - Ab initio quantum chemical calculations at RHF / 6-3 1+g(d,p) with electron correlation (MP4SDTQ) corrections have been used to investigate the stabilities of cations and anions derived from low-coordinated p-bonded phosphorus systems.* The 31P nuclear magnetic shielding tensor (o$, chemical shift (biso) and structure of dithiadiphosphatane disulfides (I), with various alkyl and aryl substituents, have been investigated by ab initio methods using IGLO (Individual Gauge for Localised Orbital) calculations* and agree with experimental values determined from solid-state CP-MAS spectra, with the most-shielded component approximately perpendicular to the PS2P ring plane. IGLO calculations have been used similarly to confirm chemical shift tensor values of phosphorus oxide sulfides, P40& (n = 0 - 4), and indicated that all magnetic shielding tensors have axial ~ymmetry.~ An ab initio examination of the Phospha-Cope rearrangement of 1,6-diphospha-l,S-hexadiene(2) into the 3,4-isomer (3) was examined at the MP4SDTQ(fc)/6 - 31G*//MP2(fc)/6 - 3 1G* and QCl SD(T)(fc)/g - 31G*// MP2(fc)/6 - 31G* level^.^ In agreement with theory, the equilibrium was found to 328

329

8: Physical Methodr

(1) R = Me, Et, c-Hex, CH2Ph, Ph, p-To1

(2) Ar

= 2,4,6-tris(t-Bu)phenyl

(3)

favour the 3,4-isomer. The reaction energy of 1.73 kcaVmol was found to be mainly due to ZPE correction which amounted to 1.30 kcaVmo1. The steric and electronic structures of tervalent aminoiminophosphines (4) have been studied by X-ray crystallography and quantum chemical calculations of aminoiminophosphines and some related model compound^.^ It was found that n +s* interaction plays a significant role in stabilising the sterically-hindered cis-form. The structural consequences of n(N) +p*(NSP) conjugation in these compounds do not correspond to the classical case and only a qualitative explanation can be given.

RN= PNR’2

(4) R = Mess,R’ = R, Piperidino

Ho\ O=P-CH2Li H d (5)

PhCHP(O)(OEt)2Li.2DABCO

(6)

The geometries of methylphosphonic acid, anion and its mono-lithiated isomers (5) have been calculated by ab initiu (MP2)(fu11)/6 - 31+G*//MP2(fu11)/6 - 31+G* and semi-empirical MNDO and PM3 methods,6 the latter giving better agreement with ab initiu methods. PM3 and MNDO methods were also used to simulate a polymeric X-ray structure of the lithiophosphonate (6) and a general PM3 study carried out to predict the dimeric structure of other lithiophosphonates. The geometry of the phosphate group in dihydrogen and dimethyl phosphates and a model diphosphate has also been studied by ab initiu calculations at the MP2 and HF level^.^ The structure of lithium bis(dipheny1phosphino) amide LiN(PPh& was aided by ab initio calculations on related lithiated model compounds.* Rotational barriers of the P-C bond in phosphoryl- and thiophosphorylstabilised carbanions have been studied by ub initio calculations on the 2-0x0(and thioxo)-2-methyl-1,3,2-diazaphosphirane-(7) and -diazaphospholidine anions (8), at MP4(SDQ)/6 - 31+G*//HF/6 - 31+G*+ZPE level^.^ MNDO calculations have shown that 2-pyrrolinones cannot be phosphorylated with phosphorus nucleophiles.lo The influence of phosphorus substituents and double bond configuration on 615N of a series of bis(imino)phosphoranes(9) has been studied by comparing the experimental 6 1 5 values ~ and ub initio-calculated values of related model compounds (l0).l1 A relationship was found between an increase in nitrogen shielding and a higher ‘ylidic’ character of the phosphorus-nitrogen double bond.

330

Organophosphorus Chemistry

1.2 Studies Based on Molecular Mechanics Theory. - Amino-imino tautomerism in thiazolium-substituted alkylidene-1,1-bisphosphonic acids (1 1) has been studied by spectroscopy and pK, measurements. The effects of pH, steric and electronic effects on the conversion of amino to imino tautomers (and on the spectra) have been confirmed by molecular mechanics calculations of their optimised molecular geometries and PPP spectra.l 2

R (R'O)zP( 0)CHzCH(OY)R (12) Y

=

H, COR2

Ph2 P(O)CH2CH(OY)R (13) Y = H, COR'

H (11) R = Me, Ph R' = H, Br, CI, NO2

Molecular mechanics (MM) modelling studies have been employed in the conformational analysis and solvation studies of 2-hydroxypentylphosphonates (12),13 and of (2-hydroxypenty1)diphenylphosphine oxide (13; Y = H) and its acetate (13; Y = COR2).l4 The studies were combined with IR spectroscopy and molecular weight determinations. MM modelling studies indicated that the relationship between the tilH chemical shift difference of the diastereotopic a-methylene protons and the population of the major conformer was due to specific solvation. MM docking studies indicated that aromatic solvents associate preferentially with the hydrophobic face whilst chloroform and methanol preferentially solvate the polar face of the amphiphilic structure. In (2-hydroxypenty1)diphenyl phosphine oxide (13; Y = H) MM modelling and IR spectroscopy indicated that the phosphine oxide favours different conformers in the solid state and in solution. Vicinal proton-proton coupling constants and MM modelling solvation studies indicated that there can be substantial deviations from perfectly staggered conformers.

2

Nuclear Magnetic Resonance Spectroscopy

2.1 Biological and Analytical Applications. - Reports concerning the use of 31P NMR spectroscopy in biology with respect to the study of in vitro and in vivo metabolic processes are too numerous to cover in detail but important general reviews and applications are noted below.

8: Physical Methodr

33 1

Multinuclear ('H, 31P and 13C) NMR spectroscopy of biological samples, reflecting their metabolic composition, has been reviewed. Reported advantages include the analysis of high field and high resolution spectra of biological matrixes requiring no separation into individual metabolites, pattern recognition methods to classify samples, stable isotope-enriched precursors to follow biochemical pathways, and volume selective in vivo spectroscopy or imaging (MRI) to depict acute and time-dependent metabolic events non-invasivelywithin a few minutes. A very exciting in vivo application is the development of paramagnetic complexes as novel NMR pH indicators.16The system is based on the remarkable pH dependence of the chemical shift separation (7.0 & 0.1 ppm/pH unit) observed between the outer 'H NMR resonances on the spectrum of the ytterbium complex, Fb(dotp)]'- (14) in the pH range 5.0 - 7.5 at 39"C, where Hgdotp represents 1,4,7, 1O-tetraazacyclododecane-N,N',Nf,N'''-tetrakis-(rnethylene-phosphonic acid).

31PNMR profiling of phospholipids has been reviewed17 and the dependence of 31P NMR chemical shifts with solvent composition, in the analysis of phospholipids in a chloroform /methanol / water ternary system, has been discussed.ls A quantitative 31PNMR analysis procedure has been described19 for the determination of phospholipids of erythrocyte membranes. Analytical (non-biologicat) applications are described under the appropriate physical method below, but 31PNMR spectroscopy has been used to detect trace amounts of chemical warfare agents and related compounds in environmental samples using a combination of 'H and "P NMR spectroscopy.20

2.2

Chemical Shifts and Shielding Effects - Positive chemical shifts are downfield of the external reference 85% phosphoric acid, and are usually given without the appellation ppm. One coordinate compounds studied include phosphaalkynes (15 ) as shown in Scheme 1. "P-NMR spectroscopy showed that, in the presence of Lewis acids derived from group 13 elements, phosphaalkynes undergo spirocyclotrimerisation with incorporation of the Lewis acid to form the betaines (16).21Signals of three different phosphorus environments were observed at 6 = -87.5 to -78.1, 257.4 to 262.2 and 412.3 to 422.4, the downfield shifts of the latter two resonances

2.2.1 Phosphorus-31 NMR.

332

Organophosphorus Chemistry

R But R (16) R = Bu', E =At, X = CI

'But (19)

Scheme 1

showing the presence of two phosphaalkene units whereas the third resonance at higher field appeared in the range typical of phosphireniwn ions. Reaction of the t-butyl spirocyclotrimer (16) with the Lewis base, dimethyl sulfoxide, generated two isomeric triphospha 'Dewar benzene' derivatives, (17) and (18). It was shown that both can be trapped by further reaction with the phosphaalkyne, in a homo Diels-Alder addition, to give respectively, the two novel phosphaalkyne cyclotetramers, (19) and (20), (Scheme 1). Characteristic of (19) is the high-field absorption at 6 = - 160 in the phosphirane system and the low-field absorption at 6 = +417.1 as a doublet, 'Jpp = 264.8 Hz, typical of a phosphaalkene unit. The resonance (6 = +134.3) had the same coupling constant which indicates the juxtapositions of the two phosphorus atoms. Another signal at 6 = +111.5 appears as a doublet of pseudotriplets with 2Jpp = 17-32, which is in the range typical of X303-phosphorusin comparable polycyclic systems. The structure of cyclotetramer (20) is confirmed by typical high-field signals of the diphosphirane ring system (6p = - 174.4 and - 147.3). The phosphaalkene phosphorus atom P7 appears as a singlet at (6p = +399.0. Further reaction of cyclotetramer (20), with mesitylnitrile oxide led to the pentacyclic system (21). The absence of the P=C bond was reflected in a dramatic high-field shift of about AZip = 300 of the signal of P-1 (6p = 75.6). Tandem ene reactions of phosphaalkynes with terminal alkenes have been and as part of a multinuclear NMR followed by 31PNMR spectroscopy study, 31PNMR was used to follow the reaction of phosphaalkynes with decaboranS3 to form new phosphaborane compounds (phosphine-methylene ylides), nido-RC(H)PBloH13.

8: Physical Methoh

333

Two coordinate compounds studied include the phosphaalkenes. [Bis(trimethylsily1)- methylene] chlorophosphine (22) acts as an extremely reactive enophile in phospha ene reactions with all-carbon enes of different c o n ~ t i t u t i o n . ~ ~ Reaction of chlorophosphine (22) with terminal alkenes yielded the corresponding 1:1 ene adduct - the allyl-substituted chlorophosphine (23), for example compound (24), as revealed by 31P('H}-NMR analysis with chemical shifts in the range 127.1 to 143.0, typical for dialkylchlorophosphines.31P('H}-NMR spectroscopic analysis indicated that dimethylallene undergoes addition to (22) to yield the chlorophosphino-substitutedbuta-l,3-diene (25), identified as a singlet at 2jp = 115.3, whereas allene itself reacts with chlorophosphine (22) to give the propynyl-substituted chlorophosphine (26) tip = 120.8. Chlorophosphine (22) also reacted with but-2-yne forming the chlorophosphinoallene (27), similarly characterised as a singlet at Zip = 117.9.

Halogenation and dissociation of a diphosphonio-l,2,4-triphospholidehas been studied using 31PNMR spectro~copy.~~ The triphospholide cation (28), as the halide, exhibits a cyclic delocalised bonding system and can take up to two moles of halogen to form trihalo- triphospholanes (29).

x*.

P-P

Ph3P

+Ph3

c I(28)

PhJPA

x,

pXPPhg

.

X

(29) X = Hal, CF3, SO3

Three coordinate compounds - A series of bis(triphenylphosphoniumylidy1) phosphines (30) have been prepared. As shown by the 31PNMR spectrum in solution and X-ray crystallographic analysis, in particular of phosphoniophosphine (31), the lone pair at the tervalent phosphorus is generally oriented synperiplanar to both phosphonio groups.26 The molecular structures of diphosphadisilacyclobutanes (32) and (33) were also deduced using NMR.27 Reaction of the diaza- phosphole (34) with dialkylthio- and dialkyldithio-phosphoric

Organophosphorus Chemistry

334

acids28 yielded diazaphosphine (35), characterised by the resonance of the endocyclic P(II1) atom being shifted upfield due to the intramolecular P-S interaction, and having a thione structure (35; R = Et, Ch = 0). Li

(30) X = H, D, R, NPhR, SnPH3, OMe PPh2, pyrrol, NTmQ, P(Y)PhZ

(31)

H (32) Cp’ = Me5C5

Me

Four coordinate compounds - As usual, a lot of work has been carried out on four coordinate compounds. A 1,4-dihydro-1h5,4h5-[ 1,4]-diphosphinine-1,4-disulfide (36) and the thio- acetamide analogue 1,2,4,5tetraphenyl-1,4-dihydro1h5,4h5-[1,4]-diphosphinine (37) have been studied by NMR.29A 31PNMR study of phosphinous, phosphinic and thiophosphinic amides revealed that the 63Ip chemical shifts of the tertiary amides, e.g. (C1CH2)PhP(0)NPr2, are at lower magnetic field than those of the secondary amides, except in the bis(t-butyl) series where the trend is reversed.30 2,10-Dichloro-6-aryloxy-l2H-dibenzo[d,g]-[l.3.2]dioxa- phosphocins (38) have been synthesised and chemical shift values reported on a series of 13 new compounds, with 631p values in the range +52.3 to +55.1.31 The NMR data tentatively suggests a boatchair as the major conformer for the central 8-membered dioxaphosphocin ring. ‘H, 13C and 31PNMR spectroscopy showed that two diastereoisomers of the adduct (39) are formed in the reaction of 2-0x0-2-hydro-1,3,5-trimethyl-1,3,5-triaza-2h4-phosphorine-4,6-dione with 3-thia~olines.~~ Extensive NMR studies of dialkyl (2-hydroxyalky1)phosphonates(12; Y = H) and their carboxylic esters (12; Y = COR) revealed 631p values in the range +28.33 to +37.39 in the former, and +29.24 to +33.22 in the latter class of compounds.33 The 31P signals of the (2-hydroxyalkyl) phosphonates are deshielded relative to those of the corresponding carboxylic esters, which can be explained by the involvement of the phosphoryl oxygen in a hydrogen bond, decreasing the p-back-bonding to phosphorus. The presence of metal salts in acetone-d6 solutions of both the phosphonates and their esters caused marked downfield shifts of the 31Psignals confirming the coordination of the metal ion to the phosphoryl oxygen, the effect increasing in the order Na+ < Li+ < Zn2’.

335

8: Physical Methods

d (36)

S

Cl

(38)Ar

(39)R = R' = R2 = R3 = Me; R' = Et; R2R3= (CHZ)~

= substituted phenyl

The reactions of trialkyl phosphites with dialkyl benzoylphosphonates have also been extensively s t ~ d i e d .At ~ -higher ~ ~ temperatures, novel ylidic phosphonates (40) are produced via phosphite trapping of intermediate carbenes. Ylidic phosphonate (40; R = PhO) had characteristic 31PNMR signals at 631p at 53.5 and at 31.6. The phosphate (41; R = PhO), was frequently observed in the reaction products and had a very characteristic 31PNMR spectrum with at 19.4 (P(0)(OMe)2) and at 1.5 (OP(0)(OMe)2). Aryloxo derivatives of phosphorus(V) porphyrins (42) have been fully characterised by a combination of techniques. The proton-decoupled 8 3 , signal ~ (- 194 to -200) suggests that an octahedral coordination around the phosphorus exists.37

0 OMe R ' +P(OMe)3 (41)

TpTP = dianion of ietia-p-tolylporphyrin and OR is axial OAr ligand

Degradation of cyclophosphamide, in neutral or slightly acidic aqueous solution, gives initially an intermediate bicyclic compound which hydrolyses immediately and exclusively to a 9-membered heterocycle, whereas thermal degradation of solid cyclophosphamide yields the bicyclic compound (43), all the structures The isophosphindoline being established by 'H and 31P NMR spectro~copy.~~ heterocycle (44)has been synthesised and characterised by NMR spectros~opy.~~ Dihydrophosphete heterocycles have also been synthe~ised.~~ l-Phospha-3phosphonium-2-dithiocarboxylato1cyclobutane (45) is thermally unstable and converts quantitatively into 3-thioxo-3,4-dihydro-1A5-diphosphet-2-ylphosphono

336

Organophosphorus Chemistry

Me (47)

R2(0) PHP(0)R2 R2P(O)CrNO

*

N\o,"o (48) R = morpholino

(49)

thioic bis(dimethy1amide) (46),and the 2,4-substituted-3-thiox0-2,3-dihydro-l ASphosphete analogue (47)is produced by reaction of the 2,4-substituted derivative of (45)with carbon disulfide. All new compounds have been characterised and NMR isotope effects on i531p of phosphete (47) studied. Other compounds characterised using 31PNMR include dimorpholinophosphorylnitrile oxide (48) and its dimeric reaction product, the furoxan (49).411-Aryl-5-trifluoromethylimidazole-4-phosphonates (50)have been studied and an excellent correlation found between log 631pchemical shift and CT shielding parameters of nuclear substituents on the aromatic ring.42 2-Aryloxy-5,5'-dimethyl-l,3,2-dioxaphosphorinone-2oxides (51),43 and 2-benzylthio-3-cyano(ethoxycarbonyl)-5-aryl-6-phenyl-6-0~06-phospha-4,5,6-trihydroimidazolo[2,3-e]pyrazoles(52) have been synthesised and structures determined using 31P NMR spectroscopy, the latter having the trans phenyl groups configuration.44 Hitherto unknown bicyclic phospholane esters (53; R = H and R' = Ph, Et) and a substituted-l,3,2-dioxaphosphorinane (54),451,3,5-triam-7-phosphoniaadamantane salts (55) and their reductive 'cage' cleavage product (56) which has a novel bowl-shaped N-methyl-P-alkyVaryl [3.3.1J bicyclononane ligand have been similarly characterised.

Me (51) Ar

= Tol,

H 4-nitrophenyl

(52)

337

8: Physical Methodr 0

0

H H

R

(53)

(55) R = Me, Et, But, HexC,PhCH2, Ph X = CI, I, PF6, BPh4

(56) R = Me, Ph

New unsymmetrical diphosphazanes (57) have been prepared and converted into mono-and dioxides or sulfides. These compounds have been characterised by NMR and variable-temperature 31P{'H} NMR measurements. Some of the compounds have been shown to exist in different types of conformer in solution.'" The structures of amides (58) and (59) have been further confirmed by X-ray diffra~tion.~'a-Aminoarylmethane phosphonic acids (60) have been prepared with a range of fluoro, fluoroalkyl, or fluoroalkoxy substituents in the benzene ring and, being of relatively low aqueous solubility, their NMR spectra were recorded in D20 in the presence of excess alkali.48Under these conditions, the ring substituents appear to have little effect on the 831p chemical shifts values of 15-18, or on the 61H and 8 1 3 ~values for the benzylic group (a-CH). New dibenzophosphaselenocine heterocycles (61) and (62) have been prepared from reactions of the bisbromide (63, X = PhP(0)) with sodium selenide, and from bis(bromomethy1)phenyl selenide (63, X = Se), all structures having been determined by multinuclear NMR and X-ray diffraction methods.49 Solution and solid-state proton transfer from phenols to triphenylphosphine with several oxide has been studied by 'H, 13C and 31PNMR spectros~opy,~~ complexes between substituted phenols and triphenylphosphine oxide having been examined. The degree of proton transfer in solution was studied by the tilH value of the phenolic OH proton and by the 813~values of the phenol C-0 ((2-1) and para (C-4) carbons. The solid phase was studied through the changes in the 31Pshielding tensor of the triphenylphosphine oxide residue and by the C-1 and

(57) X = Ph, YY' = 2,2'-biphenyldioxy X = Ph, YY' = 2,2'-binaphthyldioxy X = Ph, Y = Ph, Y' = OAr X = Ph, Y = Ph, Y' = N2C3HR2

(58)

(59)

338

Organophosphorus Chemistry

k' (60) R' = 2-F, 3-F, 4-F, 3,4-F2, Fg, 4-CF3,3-CF3,4-0CF3

i r

i r

(63) X = Se, PhP(0)

C-4 6 1 3 values ~ of the phenols. The values of the principal components of the 31P shielding tensor ( ~ 1 1 ) move towards those corresponding to symmetrical, tetrahedral phosphorus environments as the pK, of the phenol decreases. Five and six coordinate compounds Some five coordinate phosphorus compounds have been examined and qualitative relationships between S31p value and chemical structure demonstrated based on ring strain and p-b~nding.~' An NMR study of an addition reaction of spirophosphoranes (having a P-H bond) with tetraethyl- and tetramethyl-ethenylidine biphosphonates has been carried out.52 Michael-type addition of six different spirophosphoranes, e.g. (64; X = H) with tetraethyl- and tetramethyl ethenylidine biphosphonates gave established spirobiphosphonates, e.g. (64;X = X' = CH2CH[P(0)(OR),]), which have been examined by 'H, 13Cand 31PNMR spectroscopy. The mechanism of the reaction of hydridophosphorane (65) is discussed. New difluorophosphoranes (66 - 73) containing bulky substituents have been prepared and characterised by 'H, 31P The synthesis and reactivity of the first NMR and 19F NMR spectro~copy.~~ spectroscopically-observed 1 H-diazirine (74) is reported.54 Thus as shown in Scheme 2, bis-(phosphin0)nitrilimine (75) reacts at - 50 "C with tetrachloro-obenzoquinone to give intermediate (74), S31p 58.5 and 2.6, which rearranges above - 30 "C into phosphorane (76), S31p 56.5 and -24.1 Me.

Me

8: Physical Methoa5

339

Scheme 2

The synthesis and characterisation of neutral hexacoordinate phosphorus(V) compounds (perphosphoranides) containing divalent tridentate diphenol imino, azo and thio ligands has also been reported.55The hexacoordination was revealed by their high-field 631p values, characteristic JpF coupling and crystal structures. Two compounds of particular interest are the trihaloperphosphoranides (77; Hal = C1, F), with respective 831p values of - 136.4 and - 136.9.

2.2.2 Selenium-77 NMR.

- The 677% values of the new dibenzo-phosphaselenocines (61-62) are reported49 and solid-state (CP/ MAS) 31Pand 77SeNMR data was used to aid the structure elucidation of selected organophosphorus dichalcogenide~,~~ i.e. bis[( 1,2:3,4-diisopropylidene)-a-D-galactopyranosyl-6-0-60-thiophosphoryl] disulfide and bis[5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinan-2-ylI diselenide. Different polymorphs of both compounds were evident. Characterisation of organochalcogeno (78)- and phenyl [(triphenylmethyl)imino]- phosphonic N-(N’,N’,N”,N”-tetramethy1)guanidine fluorides has been aided by 77Se and ”’Te NMR spectroscopy and the final structures confirmed by X-ray ~rystallography.~~

340

Organophosphorus Chemistry

(78) R = Ph, Ch = S R = But, Ch = Se

2.2.3 Carbon-I3 NMR. - Specific 13C NMR data of 1,3,2-oxazaphospholidine derivatives (79) are reported.58The use of phosphorus J-scaled proton-carbon 2 0 NMR for 31Pcoupling constant measurements is also reported,59for example in the 31P J-scaled 'H-13C correlation spectra of the DNA aptamer d(GGTTGGTGTGGTTGG). Characterisation of phosphine-borane complexes of phosphorus-heterocycles (80-85)has been aided by 31P, "B and I3C NMR data.60The quaternary carbon atom in diazirine (74), 8 1 3 c 151.1, is typical of an imine carbon but the effects of the three membered ring and the bound phosphorus group may be ~ a n c e l l i n g . ~ ~

oMe pJe CI

n ,NYAr

0 ,

J\NEt2

S

(79) Y = s02, co; Ar = substituted phenyl

CI

$ M -e-(

/ \

ph/ 'BH2X

R

/ \

R

BH3

BH3

(82)

(81)

(80)

R-

BH2X

Ph'

'BH3

2.2.4 Hydrogen-I NMR. - A proton magnetic resonance spectral study of 0,O'bis(ary1) isobutyl phosphonates (86) indicated that the 31P splits the a- and P-protons of the isobutyl group.61The apparent coupling constant JcH,cH, of aprotons has been found to be different in the two halves of the double doublets, and the two electronic parameters G and F give good predictive models for chemical shift values of a and aromatic protons. Diazacyclophosphamides (87,88) and oxaazacyclophosphamidicchlorides (89) have been used as reagents for the determination of the optical purity and absolute configuration of amines and a l ~ o h o l s . These ~ ~ - ~ have ~ been readily determined by 'H and 31PNMR data of the cyclophosphamide derivatives that are formed in these reactions. 'H NMR data has also been used (together with other data) in the structural determinations of diorganotin bis-O-alkyl phosphonates (90)," of N-( 1-oxo-1-phospha-2,6,7-trioxabicyclo-[2.2.2]octane-4-car-

8: Physical Methodr

34 1

.

0:

.

\-Yph

bony1)-Naryl(a1kyl) thioureas (91)65 and of fused phosphorus heterocyclic compounds (92).66 In porphyrin (42) the ring-current induced upfield shifts for the protons on the two axial aryloxo ligands in the ‘H NMR ~pectra.~’ 2.2.5 Other NucleilMultinuclear NMR.

- Various 15N parameters - 815N, ‘JpN and 3 J p ~and , 1D’5”4N(31P)of seven phosphazenes, e.g., MePh,P=NPh, in natural abundance based on 1D and 2D indirect 31P-detectionspectroscopy has been described.67 The first lithiumsilanyl-lithiumphosphanides, R‘2Si(Li)-P(Li)SiR, (R= 2,4,6-iPr&H~), have been prepared and isolated and their constitution established by multinuclear NMR.68 The use of multinuclear NMR spectroscopy in the characterisation of bromophenyl [tris(dimethylamino)phosphine selenide] tellurium(I1) and tris(dimethy1amino)phosphine sulfide is reported.69

(91) R = 4-BrCsH4

(90)R = Me,Et; R‘ = Me,Et, Bu, Ph

‘X2 H, 441, X2 = H X’ X2 = OCH20 R = H, +Me; Z = N, CCN

(92)X

=

342

Organophosphorus Chemistry

2.3 Restricted Rotation and Pseudorotation. - Dynamic 31PNMR spectroscopy of lithium bis(dipheny1phosphino) amide gave an 8.1 kcal/mol rotation barrier around the PN bonds.7 The CP/MAS spectrum of the solvate has a single 6Li line, whereas the 31PCP/MAS spectrum reveals the chemical non-equivalence of the phosphorus sites. The appearance of two 31P signals indicates a minimum activation barrier for the P,P-exchange process of AG 13.4 kcallmol. 6Li and 31P NMR spectroscopy indicated that the monomeric structure in THF solution is similar to the X-ray structure of a solid 5.3 THF solvate. The phosphorus-carbon rotational barriers in the anions derived from Pmethylphosphonic diamide (93; Ch = O) are lower (6.7 kcal/mol) than the barrier (9.8 kcal/mol) for the thiophosphoryl analogue (93; Ch = S). This difference has been attributed to stronger backbonding from oxygen to phosphorus which destabilises the ground state geometry in which the lone pair on carbon interacts with the same sigma antibonding orbital,70 which is supported by experimental evidence for a short strong, polar P=O bond with a bond order greater than that of the P=S bond.71The five membered ring analogues show the same behaviour and calculations show that the transition state structure for rotation about the P-C bond has a pyramidal carbanion with the lone pair of electrons perpendicular to the P=Ch bond in both series.72

2.4 Studies of Equilibria, Configuration and Conformation. - Conformational analysis of trihalo- triphospholanes (29) by low-temperature 31P NMR spectroscopy revealed the presence of two conformer^.^^ The ylidyl substituent of the chlorophosphine (94) exerts a strong influence on the P-C1 bond. The ylidyl chlorophosphines (94; R = R2N) are covalent in benzene but become more or less ionic in dichloromethane solution. The solvent dependent dissociation equilibrium can be followed by 31P NMR spectroscopy. In the case of an enamine-derivedylidyl chlorophosphine, the equilibrium shifts almost completely from the covalent to the ionic side within a rather narrow range of solvent composition, from 20 to 70% (vol) of di~hloromethane.~~

8: Physical Method

343

The conformational preferences of three and four co-ordinate 1,3,2-0xazaphosphorinanes (95) and 1,3,2-dioxaphosphorinanesas determined by 'H, 31Pand 13C NMR spectroscopy have been reviewed.74 Unlike the four co-ordinate 1,3,2dioxaphosphorinanes (96), a Me2N substituent on phosphorus in the three coordinate oxazaphosphorinanes (95) rather surprisingly was more stable in an ~~ axial orientation when the N substituent was phenyl or i ~ o - p r o p y l .The preferences were attributed to vicinal repulsions beween N and P equatorial substutuents and anomeric stabilisation due to overap of the electron pair on the cyclic N with the axial sigma antibonding orbital. Changing the N substituent to methyl removes this strong preference and a chair - chair equilibrium is set up with the equatorial Me2N group having a slight preference for an equatorial ~ r i e n t a t i o nThis . ~ ~ trend is the reverse to that found for four co-ordinate 1,3,2oxazaphosphorinanes. The absolute configurations of amines and alcohols can be readily determined by 'H and 31PNMR spectroscopy of the cyclophosphamides formed by reaction with diazacyclo- phosphamides (87, 88) and oxaazacyclophosphamidic chlorides (89).62*63 Conformational analysis of (2-substituted-alky1)phosphoryl compounds (12,13) has been extensively st~died.'~-'~*'' In one study, the conformational populations were examined in six solvents of different polarities and in the presence of metal ions.77 Steric effects were studied by variation of the size of alkyl groups R and R and intramolecular interactions studied by derivatisation of the hydroxy group. In (2-hydroxyalky1)phosphonates the most stable conformer, ga, is that in which the phosphoryl group is gauche to OH and anti to R and it is favoured particularly in less polar solvents. In polar solvents the population of the less stable conformer, ag, in which the phosphoryl group is gauche to R and anti to OH, is increased. As expected smaller alkyl groups allow more conformational freedom. Conversion of the OH group to its carboxylic ester reduces the population of ga so that for, R = Pr, conformers ga and ag are approximately equally populated. The presence of metal salts in acetone solutions causes an increase in ga in both the hydroxy and carboxylic ester compounds. The chemical shift difference between the diastereotopica-methylene protons was found to be proportional to the population of conformer ga. Molecular mechanics modelling indicated that the above relationship is due to specific solvation. Conformational analysis of (2-hydroxypenty1)diphenylphosphine oxide and its acetate,14 by a combination of NMR, X-ray, IR and molecular mechanics (MM) modelling, indicated that the phosphine oxide favours different conformers in the solid state and in solution - their conformational preferences being strongly influenced by the nature of the hydrogen bonding. The extent of deviations from perfixtly staggered conformations was estimated through vicinal proton-proton coupling constants and MM modelling solvation studies. Conformational analysis based on the twisted staggered conformers for the phosphine oxide made marked changes to the estimated conformational populations. For the acetate, NMR spectroscopy established that the position of the conformational equilibrium is strongly dependent on the polarity of the medium, e.g. 17% conformer ga in tetrachloromethane but 63% conformer ga in methanol.

'

344

Organophosphorus Chemistry

'H NMR spectroscopy, primarily through vicinal POCH coupling constants, has been used to study the conformational preferences of 1,3,2-dioxaphosphorinanes incorporating a five co-ordinate phosphorus atom (97). Whilst X-ray crystallography showed the phosphorinane ring of phosphorane (97; R = H) to be bound to the radial bonds of p h o ~ p h o r u s the , ~ ~vicinal couplings indicated a predominance of one chair conformation - probably that shown. Unlike dioxaphosphorinanes involving apical equatorial bonds to five co-ordinate phosphorus, the 'H NMR spectra of the C-5 substituted analogues (97; R = Me, Ph, tBu) showed no evidence for the presence of boadtwist conformations and supported the presence of axial C-5 substituents with the ring occupying the diradial positions of the tbp phosphorus atom. This contrasts with the diequatorially substituted three and four co-ordinate dioxapho~phorinanes.~~

Other Studies.- The 31PNMR chemical shifts of alcohols, carboxylic acids and phenols phosphitylated with 2-chloro-4,4,5,5-tetramethyl-dioxaphospholane have been correlated with substituent effects of phenols.79 31P NMR spectroscopy has also been used to study activation pathways of aryl Hphosphonate ester condensation reactions,s0 the conversion of allenyl and divinylphosphines to 1- and 2-phosphadiene~,~' the reaction of tetraphosphorus decasulfide with dialkyl disulfides,s2 the reaction of phosphine with cyclic ole fin^,^^ the chemical shift tensors of powder samples of phosphole derivative^,^^ the reactions of alcohols and mercaptans with tetraphosphorus trichalcogen d i i o d i d e ~ the , ~ ~structure of aminomethanebisphosphonic acids,86and reactions of 00-di-(2-ethylhexyl)dithiophosphoricacids.87 2.5

2.6 Spin-Spin Couplings. - Jpp coupling- The direct coupling in the spectra of cyclotetramer (20) was 83.0 Hz and the geminal coupling 31.2 Hz. Vicinal PCNP couplings of 13 Hz are reported for the first spectroscopically-observed 1Hdiazirine (74) at - 50 "Cin dichloromethane-d6,Mand Jpp values of 93 and 34 are reported respectively for the ylidic phosphonate (40) and phosphate (41).34-36 JpF coupling- In the trifluoro compounds (77) typical 'JpF coupling values are in the range 813-842 (axial) and 745-770 Hz. (radial).8g In the imino perphosphoranide (76), the 3 J p ~values (17-27) and the 4 J ~ Hvalue (2.1) indicate strong coordination of the N atom. Jpc coupling- The magnitude of 3 J p values ~ for dialkyl (2-hydroxyalky1)phosphonates and their carboxylic esters33and (2-hydroxypenty1)diphenylphosphine

8: Physical Methoak

345

oxide and its acetates9 have been used to assign 'H NMR chemical shifts to nonequivalent a-methylene signals. JpH coupling - An interesting long-range coupling, 4JpH of 3.6 Hz is observed between phosphorus and one of the bridged methylene protons in the boat-chair conformer of novel dioxapho~phacins.~~ A recent publication on the determination of the structure of geometric isomers of phosphoruscontaining ethylenes is based on 2JpH and 3JpH coupling constants between the phosphorus nucleus and vinyl protons.'*

3

Electron Spin Resonance

The first examples of triplet-state phosphoryl and phosphinyl diradicals have been r e p ~ r t e d .Photo-induced ~~,~ dissociative electron capture of two diastereoisomeric m-phenylenebis-(phosphinicchlorides) (98; Y = 0),in a glassy toluene matrix at 130K using an electron-rich olefin, gave the corresponding phosphoryl monoradicals and triplet-state diradicals (99; Y = 0) in a 5:2 ratio. The tripletstate ESR spectrum had zero-field parameters of ID/hcll = 0.0120 an-' and IE/ hc( = 0.0015 cm- Variable-temperature ESR experiments revealed Curie behaviour for Dms = 2 ESR signals between 3.8 and 100K, consistent with a low-energy triplet-state. For the corresponding p-phenylene diastereoisomers, no triplet-state diradicals could be detected under identical experimental conditions and the ESR spectra only revealed primary phosphoryl monoradicals and their protonated forms as secondary species. Triplet-state phosphinyl diradicals (99; Y = lone pair electrons)) have also been formed by photo-induced dissociative electron capture of a sterically-hindered m-phenylenebis(phosphinous chloride) (98; Y = lp) in the presence of an electron-rich olefin at llOK. Novel triplet ground-state phosphinyl diradicals were also characterised using ESR spectra.g0 Phosphoenol radical cations have been generated in solution by one electron oxidation of enol phosphates, phosphites and phosphinates. The radicals were monitored by ESR and by cyclic voltammetry. They have been shown to undergo an unprecedented P-0 bond cleavage in s o l ~ t i o n . ~ '

'.

R

R = But; Y = 0, lone pair electrons Phm= m-phenylene

346

4

Organophosphorus Chemistry

Vibrational and Rotational Spectroscopy

The use of IR spectroscopy data (as a complementary tool) to characterise organophosphorus compounds is abundant in the literature and further applications are cited.92-97IR spectral data were combined with dipole moment measurements in the study of the polarities and conformations (in solution) of 2thiophosphoryl-l,3-dithianes( IR specroscopy has also been used in the characterisation of antimony derivatives of thioimidodiphosphinicacids,93in the study of Pt catalysed oxidative P-0 and P-C coupling of butanol and phosphine,% and in the analysis of various complex on^,^^ and 1,2-diphosphino b ~ r a n e s FT-IR . ~ ~ and FT-Raman spectroscopy have been used in the spectral interpretation and qualitative analysis of organo-phosphorus pesticide^.^^ FTRaman spectroscopy is a selective and safe technique for the qualitative identification of organophosphorus pesticides and is not accompanied by sample photo-decomposition. Combined with X-ray and differential scanning calorimetry (DSC) techniques, IR spectroscopy has been used in the characterisation of new organic-cation cyclohexaphosphate (10 1)98and the phosphonium chlorides (102,103)99and bromides.lm A study on the vibrational analysis and normal coordinate analysis of trimethylphosphine has been carried out in the liquid phase using Raman spectra recorded with parallel and perpendicular polarisation. Normal coordinate analysis was used for the vibrational assignments.lo'

(100) R = H,But; R' = Me, Ph Ph4PCI[(MeNH)2CO]

5

(1011 (Ph4P)2Cl[(MeNH)2CO]C12

Electronic spectroscopy

5.1 Absorption Spectroscopy. - UV / Visible spectroscopy has featured in the characterisation of the aryloxo derivatives of phosphorus(V) porphyrins, (42).61 Each new porphyrin showed a characteristic absorption spectrum indicating the presence of a P(V) ion in the porphyrin cavity.

5.2 Fluorescence Spectroscopy. - A method for the spectrofluorimetric determination of six organophosphorus pesticides has been established.lo2 The fluorescence of the solutions was measured at excitation wavelength, 380 nm and emission wavelength, 488 nm. The optimum pH for measurement is 9.3 - 9.6 and transition metal ions interfere but can be removed by complexation. Detection limits varied between and loA3dml, depending on the substance. There are

8: Physical Methods

347

numerous references to the use of fluorescence detection in liquid chromatographic (LC) analysis, e.g., in the analysis of aliphatic anionic surfactants. lo3

6

X-ray Diffraction (XRD)

6.1 Twocoordinate Compounds. - The steric (and electronic) structures of cr3h5-aminoimino-phosphines (10) have been studied by X-ray crystallography, and by quantumxhemical calculations. Diphosphino-l,2,4-triphospholides (28)have also been examined by XRD.25 6.2 Three-coordinate Compounds. - X-ray crystallography of lithium bis(diphenylphosphin0) amide 5.3 THF solvate showed that the lithium has a pentacoordinated distorted trigonal bipyramid environment; two THF oxygens and the nitrogen of the bis(phosphino)amide in the equatorial positions, but the third oxygen and a phosphorus are apical. The structures of diphosphadisilacyclobutanes(32), the bicyclic (33) and related compounds have been established using both X-ray and NMR technique^.^^ X-ray characterisation of enantiomerically pure l,l’-dipheny1-3,3’,4,4‘-tetramethyl-2,2’biphosphole (104), a ligand with axial and central chirality, is of potential interest. The stereochemical analysis and characterisation of diastereoisomers of (104) reveal its potential use for asymmetric catalysis. In dichloro (1,3dimethyl-2-imidazol-2-ylideneimino) phosphine, strong P-N n interaction is ‘ revealed by X-ray analysis, with P-N bond-length of 1.579 A.lo5The structure of a tetraaryldiphosphorus cation (105) and a dialkyl-phosphonium salt has also been revealed by X-ray analysis.lo6An X-ray crystallographic study of (94; Ar = Ph, R = Me) reveals the longest P-Cl bond ever observed for an acyclic chlorophosphine (226.2pm), which was attributed to a conformation that allows an exceptionally effective negative hyperc~njugation.~~

Me Ph

6.3 Four-coordmate Compounds. - The geometry of the phosphate group (and its interactions with metal cations) has been studied6 in the crystal environment by analysing XRD data from 178 crystal structures, and in vacuo by ab initio calculations of dihydrogen- and dimethyl phosphates and a diphosphate model

Organophosphorus Chemistry

348

'B"'

(107) Ch = 0, S

system. The X-ray structure of a new organo P-0-S heterocycle (106) reveals fused C3P2S and C202P2S rings.lo7 The structures of the first representatives of oligoarylene phosphocyclanes (107) have also been confirmed by X-ray analysis.lo* There is evidence for an extension of coordination by intramolecular NP donor-acceptor interaction in (8-dimethylamino-1-naphthy1)diphenylphosphine (1 08) and derivatives, as shown by X-ray crystallographic determination.lo9 The crystal structures of ylidediyl halophosphine oligomers (109) have been confirmed by X-ray analysis and specifically those of (1 lo), for n = 2, and (lll), for n = 4, have been described.'l0 The first example of a crystalline complex of a hydrophosphoryl compound with a phenol (1 12) has been described and its molecular structure determined by X-ray crystallographic analysis. * CI

I

CI (110) n = 2 Z = PPh2, P(Ch)Ph2, 6RPh2X (where R = Me, X = I; and R = CH2C@Et, X = Br)

(Ph3P=CPX),

(lll)n=4

Phosphorylation of calix(4)arene and t-butyl-calix(4)arene produced the disubstituted product (1 13; R = H, But). The dominant conformer formed is a stereochemically-rigidcone where the angles of inclination of the benzene ring,

349

8: Physical Methoh

H

Me

o% H'!

relative to the main plane of the macrocycle, are 100.8 - 145.5'. During phosphorylation of the t-butyl compound, the stereochemically-mobile 1,2-alternate conformer is also isolated. The structure of the diphosphorylated compound (cone) has been confirmed by X-ray diffraction analysis.l12 The structure of adamantane-containing phosphazenes have been determined also. * * R

k

Five- and Six-coordinate Compounds. - The molecular structures of difluorophosphoranes (67 - 69) revealed tbp geometries. Comparison of the structural data with that of the isoelectronic anionic fluorosilicates, along with the NMR data, indicates the operation of a steric effect that increases bond length in (67) and (69) and in related anionic silicates. The crystals are in the monoclinic space group. An X-ray crystallographic study of phosphoranes examined the effect on the equatorial 0-P-0 bond angles of the inclusion of phosphorus in a 1,3,2-dioxaphosphorinanering. l4 The crystal structures of (114; RR = CH2CH(Bu')CH2) and (1 14; R = Me) were determined and found to have tbp OPO bond angles of 91.67 and 111.24 respectively. When phosphorus was included in a bicyclic ring system, these phosphoranes featured a distorted trigonal bipyramid local geometry about the phosphorus. The bond angles

6.4

O

O

'

350

OrganophosphorusChemistry

0-P-0 found for these two phosphoranes were :- apical, 162.5 and 163.3 and radial, 107.7 and 112.7 respectively. Probably, compression of the equatorial 0-P-0bond angle in the 6-membered ring of (1 14; RR = CH2CH(Bu‘)CH2)and related phosphoranes allows the ring to assume a chair conformation more easily than when phosphorus is not part of a bicyclo ring system. The only significant reference to six coordinate compounds (perphosphoranides) related to the divalent tridentate ligands in (76) and (77).55 O

O

O

O

(1 14) R = Me, RR = CH2CHBu‘CH2

7

Electrochemical Methods

7.1 Dipole Moments. - The polarity and conformation in solution of 2thiophosphoryl-l,3-dithianes (100) has been studied by the dipole moment method and using IR spectral data.92 In solution, they exist mainly as an equilibrium of two chair-like conformers with axial orientation of the phosphorus-containing substituent. The polarity and conformations of alkenylphosphine oxides (1 15) and related acetates (1 16) have also been determined. R’R2P(Ch)CX=CHR3 (1 15) R’, R2 = Ph, Me;

R3 = H,Me, vinyl X = H, CI, R3; Ch = 0, S

R’R2P(0)CH2C02R3 (1 16) R’ = Ph; R2 = vinyl; R3 = 3-menthyl

R’ = o-anisyl; R2 = Ph; R3 = 3-menthyl R’ = R2 = PhCH2; R3 = Et

7.2 Cyclic Voltammetry and Polarography. - Aryloxo derivatives of phosphorus(V) porphyrins have been studied by a variety of techniques. Cyclic voltammetric studies revealed that each porphyrin undergoes two successive, oneelectron reductions, with the site of electron transfer being the porphyrin ring.61 For the first time, phosphoenol radical cations have been generated in solution and monitored by cyclic voltammetry and ESR. The sterically-congested radical cations undergo an unprecedented P-0 bond cleavage, and the kinetics are also deter~nined.~’ In the polarography area, half-wave potentials have been employed as a tool for predicting the scope and limitation of the reaction of a,P-unsaturated ketones

351

8: Physical Methoh

'

with a phosphorus nucleophile. l 6 The occurrence (or non-occurrence) of the reaction between enones, e.g. PhCH=CHCOPh, and trialkyl phosphite, and even the magnitude of the equilibrium constant for the reaction can be predicted.

7.3 Ion-selective and Potentiometric methods A neutral, carrier-based calcium ion-selective microelectrode has been used in the determination of tetraphenylphosphonium ions (used as membrane potential probes) during respiratory-state transitions in rat mitochondria. l 7 The application of poly(cyc1ophosphazene)for the potentiometric detection of tributyl phosphate vapour is reported,' l8 and the potentiometric determination of some phosphor- amidothioates given.' l 9 Phosphine and phosphorus oxide concentration measurements with silver(1) p-alumina have also been reported.120

'

8

Acidities, Basicities and Thermochemistry

The paramagnetic complex, Tyb(dotp)]'- has shown great promise as a NMR probe for in vivo pH measurements.16 At 39°C and pH of 8.1, the'H NMR spectrum of Tyb(dotp)]'- covers a spectral region of 140 ppm. Stepwise protonation causes large changes in the chemical shifts of all the resonances. From the NMR titration curve relating to proton ac 1, pK, values for each of the stages (Figure) were calculated, respectively as 7.76 (a4), 6.56 (a3), 5.55 (a2) and 3.86 (al). The pK, evaluation of model phosphonamidic, phosphonamidothioic and phosphonamido-dithioic acids (1 17,118) and their spectral properties have been described.'*l (MeO)P(0)Me(NHCH2Ph)

MeP(0)(OH)(NHCH2Ph)

Some thermochemical aspects of reactions and products are included in the theoretical ~ e c t i o n .The ~ . ~new organic-cation phosphate (101) has been examined by differential scanning calorimetry (DSC).98

9

Mass Spectrometry

There are numerous earlier references using mass spectroscopy as a complementary technique. Mass spectrometric (MS) studies have been carried out on lH,5H-benzo[c][2,4,3]dithiaphosphepine 3-0xides,l~~ and a comparison study undertaken123between ion trap and quadrupole MS techniques for the residue analysis of organophosphorus (and organochlorine) pesticides. The use of nitrogen trifluoride (a new reactant gas) in chemical reaction interface mass spectrometry (CRIMS) for the detection of phosphoruscontaining compounds, by generation of PFs with fluorine, is described.124 The main fragment ion, PF4,+ was used to determine the detection limit. CRIMS has been used in the detection

Organophosphorus Chemistry

352

of cyclophosphamide and its metabolites in plasma. Kinetic isotope emects, involving the use of 2Hand l 8 0 , were used in the study of metaphosphate generation from the fragmentation of 2,3-oxa-phosphabicyclo[2.2.2]octene (1 19).125

kN\ Ph

0

(1 19) Y = EtO. Et2N

10

Chromatography and 'Hyphenated' Techniques

10.1 Gas Chromatography and Gas Chromatography-Mass Spectroscopy. - Gas chromatographic (GC) analysis of organophosphorus compounds in body fluids126-128has been described. There have been numerous reports on applications to food129-130 analysis and also to environmental analysis.131-136 GC-MS analysis is now widely-used in the analysis of organophosphorus pesticides and it has also been used to study the unusual reactivity of the radical cations of some simple trivalent organophosphorus compounds towards dimethyl sulfide and dimethyl selenide.146 The combined techniques of GC-MS and liquid chromatography (LC) have been used in the multi-residue analysis of pesticides in fruit and vegetables.147

10.2 Liquid Chromatography 10.2.1 High Performance Liquid Chromatography and LC-MS. - C h i d LC separations of the enantiomers of 0,O'-diethyl (p-methylbenzenesu1fonamido)aryl-(alky1)-methylphosphonates and diethyl N-(ary1)- 1-amino-1-arylmethane phosphonates have been carried out.148-149 In the case of LC, geochemical and biological applications feature, 50-153 and LC-MS has been used in environmental analysis of organophosphates. 3 1 - l ~ ~ 10.2.2 Ion Chromatography. - Organic phosphorus-containing acids and their thio- and dithio- analogues have been analysed by ion chr~matography'~~ and the microdetennination of phosphorus in .organic compounds has been accomplished.158 10.2.3 Thin Layer Chromatography. - Complex mixtures of phosphorus-32 postlabelled DNA adducts have been analysed by high-resolution anion-exchange and partition thin-layer chromatography.159

8: Physical Methods

353

10.3 Capillary Electrophoresis and Micellar Electrokinetic Chromatography Capillary electrophoresis (CE) features increasingly in chiral separations.160-163 The use of cyclodextrins as chiral selectors is commonplace. Micellar electrokinetic chromatography (MEKC) was used for the chiral separation of enantiomers of l,l'-binaphthyl-Z,2'-diylhydrogen phosphate.Im [Yb(dotp)]" + H'

[Yb(Hdotp)]" [Yb(Hpdotp)]% [vb(H,d0tp)l2[Yb(H4dotp)]-

-

[Yb(Hdotp)]"

+ H'

[Yb(H,dotp)]% + H' (vb(H,dot,,)]*-

+ H+

Scheme 3

11

Kinetics

In particular, the thermochemistry and kinetics of the electrophilic Pudovik reaction, between five- and six-membered cyclic (and acyclic) phosphorous acids and substituted morpholino- ethenes, have been studied. The high reactivity has been explained in terms of ring strain (23 kcallmol) and heats of activation of 26 kcallmol determined for the reaction.

References 1.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

W. W. Schoeller, U. Tubbesing, C. Begeman, and J. Strutwolf, Phosphorus, Sulfur, Silicon Rel. El., 1996, 109, 101. G. Ohaus, U. Fleischer, and V. Kaiser, J. Chem. Soc., Dalton Trans., 1995,8, 1297. U. Fleischer, F. Frick, A. R. Grimmer, W.Hoffbauer, M. Jansen, and W. Kutzelnigg Z. Anorg. Allg. Chem., 1995,621,2012. U. Salzner and S. M. Bachrach, J. Org. Chem., 1995,60,7101. A. N. Chernega, A. A. Korkin, and V.D. Romanenko, Zh. Obshch. Khim., 1995,65, 1823 (Chem. Abstr., 1996,125, 10 973). R. Koch and E. Anders, J. Org. Chem., 1995,60,5861. B. Schneider, M. Kabelae, and P. Hobza, J. Am. Chem. Soc.,1996,118,12207. T. Kremer, F. Hampel, F. A. Knoch, W. Bauer, A. Schmidt, P.Gabold, M. Schuetz, J. Ellermann, P.von R. Schleyer, Organometalfics,1996,15,4776. M. Kranz, S. E. Denmark, K. A. Swiss, and S. R. Wilson, J. Org. Chem.,1996, 61 8551. N. A. Polezhaeva, V. G. Sakhibullina, T. G. Kostyumina, A. V. Prosvirkin, N. I. Tyryshkin, and G. A. Chmutova, Zh. Obshch. Khim., 1996,66, 1134 (Chem. Abstr., 1997,126,8 158). D. Gudat, E. Niecke, A. Ruban, and V. von der Goenna, M a p . Reson. Chem., 1996,34,799.

354 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41.

42. 43.

OrganophosphorusChemistry

A. L. Chuiko, L. P. Filonenko, A. N. Borisevich and M. 0. Lozinskii, Zh. Obshch. Khim., 1995,65, 1338 (Chem. Abstr., 1996,124,202 414). D. G. Genov and J. C. Tebby, Phosphorus, Sulfur,Silicon Rel. El. , 1996,114,91. D. G. Genov, R. A. Kresinski, and J. C. Tebby, Heteroatom Chem., 1996,7,375. D. Leibfritz, Anticancer Res., (3B, Proceedings of the Special Symposium on 'Lipid Metabolism and Function in Cancer', 1995), 1996, 16, 1317. S. Aime, M. Botta, L. Milone, and E. Terreno, J. Chem. Soc.,Chem. Commun., 1996, 1265. T. Glonek and T. E. Merchant, Oily Press Lipid Libr., (Advances in Lipid Methodology -Three), 1996,7, 37. M. Branea, N. Culeddu, M. Frauianu, and M. V. Serrra, Anal. Biochem., 1995,232,l. M. H. Nouri-Sorkhabi, L. C. Wright, D. R. Sullivan and P. W. Kuchel, Lipids, 1996, 31, 765. M. Mesilaakso and E. L. Tolppa, Anal. Chem., 1996,68,2313. B. Breit and M. Regitz, Chem. Ber., 1996,129,489. T. W . Mackewitz and M. Regitz, Synthesis, 1996,1,100. R. W. Miller and J. T. Spencer, Organometallics,1996, 15,4293. T. W. Mackewitz and M. Regitz, Liebigs Ann. Chem., 1996,327. H. P. Schroedel, A. Schmidpeter, H. Noeth, and M. Schmidt, Z. Naturforsch.. B: Chem. Sci., 1996,51, 1022. G, Jochem, A. Schmidpeter, and H. Noeth, 2. Naturforsch., B: Chem. Sci., 1996,51, 267. M. Waltz, M. Nieger, and E. Niecke, Organosilicon Chem. II, [Muench. Silicontage], 2nd, Meeting 1994 : Edited by N. Auner and J. Weiss, VCH, Weinheim, Germany, 1996,209. N. G. Khusainova, T. A. Zyablikova, R. G. Reshetkova, and R. A. Cherkasov, Zh. Obshch. Khim., 1996,66,416 (Chem. Abstr., 1996,125,328 935). K. Bieger, G. Heckmann, E. Fluck, F. Weller, K. Peters, and E-M. Peters, Z. Anorg. Allg. Chem., 1995,621, 1981. L. Maier and P. J. Diel, Phosphorus, Suvur, Silicon Rel. El., 1996, 115,273. C.D. Reddy, P. M. Reddy, D. R. Reddy, M. Nagalakshmamma, K. Anuradha, and C. N. Raju, J. Heterocycl. Chem., 1995,32, 1483. I. Neda, T. Kaukovat, P. G. Jones, R. Schmutzler, H. Groeger, and J. Martens, 2.Naturforsch., B: Chem. Sci., 1996,51, 1486. D. G. Genov and J. C. Tebby, J. Org. Chem., 1996,61,2454. D. V. Griffiths, P. A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. SOC., Perkin Trans. I , 1995, 555. D. V. Griffiths, P. A. Griffiths, K. Karim, and B. J. Whitehead, J. Chem. Rex (S), 1996, 176. D. V. Griffiths and K. Karim, Phosphorus, Sulfur, Silicon Rel. El., 1996,111, 107. T. A. Rao and B. G. Maiya, Inorg. Chem., 1996,35,4829. U . Niemeyer, B. Kutscher, J. Engel, I. Neda, A. Fischer, R. Schmutzler,'P. G. Jones, M-C. Malet-Martino, V. Gilard, and R. Martino, Phosphorus, Sulfur,Silicon Rel. El., 1996,109,473. T. Kasaka, M. Kyoda, K. Taketazu, H. Kobayashi, T. Fujimoto, R. Iriye, and I. Yamamoto, Phosphorus, Sulfur,Silicon Rel. El , 1996,113, 59. G. Heckmann, F. Rosche, F. Weller, and E. Fluck, Phosphorus, Sulfur,Silicon Rel. El., 1996,115, 3. T. A. Zyablikova, B. T. Buzykin, A. S. Dokuchaev, M. P. Sokolov, R. M. Gainullin, and M. V. Petrov, Fiz.-Khim Metody Issled. Strukt. Din. Mol. Sist., Muter. Vseross.Soveshch. :Edited by M. E. Gordeev, Ioshkar-Ola, Russia, 1994,1,94 (Chem. Abstr., 1996,125, 142 869). C-Y. Yuan, W-S.Muang, and Y-X. Zhang, Phosphorus, Sulfur,Silicon Rel. El., 1996,115,105. K . V. Raghu and C. D. Reddy, Indian J. Chem., Sect. B: Organic Chem. Incl. Med Chem., 1996,35,1228.

8: Physical Methods

44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63.

64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76.

355

R-J. Lu, H-Y. Liu, G-F. Yang, and H-Z. Yang, Gaodeng Xuexiao Huaxue Xuebao (China), 1996,17, 1240 (Chem. Abstr., 1996,125,247 941). E. E. Nifantyev, A. M. Koroteev, M. P. Koroteev, S. V.Meshkov, V. K. Belsky, and A. R. Bekker, Phosphorus, Sulfur Silicon Rel. El., 1996,113, 1. B. Assmann, K. Angermaier, M. Paul, J. Riede, and H. Schmidbaur, Chem. Ber., 1995,128,891. R. P. K. Babu, K. Aprna, S. S. Krishnamurthy, and M. Nethaji, Phosphorus, Sulfur,Silicon Rel. El., 1995, 103, 39. D. St. C. Green, U. Gruss, G. Haegele, H. R. Hudson, L. Lindblom, and M. Pianka, Phosphorus, Sulfur,Silicon Rel. El., 1996,113, 179. H. Fujihar, T. Nichioka, H. Mima, and N. Furukawa, Heterocycles, 1995,41,2647. C. M. Lager, U. Scheler, G. McGeorge, M. G. Sierra, A. C. Olivieri, and R. K. Harris, J. Chem. Soc., Perkin Trans. 2, 1996, 1325. G. Li, L. Liu, R. Cao, S. Zhang, and L. Fu, Bopuxue Zazhi (China), 1995, 12, 87 (Chem. Abstr., 1995,123, 133 298). R. Burgada and T. Bailly, Phosphorus, Sulfur,Silicon Rel. El., 1995,103, 125. R. R. Holmes, J. M. Holmes, R. 0. Day, K. C. Swarug, and V. Chandrasekhar, Phosphorus, Sulfur,Silicon Rel. El., 1995, 103, 153. N. Dubau-Assibat, A. Baceiredo, and G. Bertrand, J. Am. Chem. Soc., 1996, 118, 5216. C. Y. Wong, R. McDonald, and R. G. Cavell, Inorg. Chem., 1996,35,325. M. J. Potrzebowski, Wiad. Chem. (Poland), 1995, 49, 777 (Chem. Abstr., 1996, 125, 10 940). J. Muenchenberg, H. Thoennessen, P. G. Jones, and R. Schmutzler,Z. Naturforsch., B: Chem. Sci., 1996,51,1150. D. Zhang, M. Zhang, and H. Jiang, Bopuxue Zazhi (China), 1996, 13,423 (Chem. Abstr., 1997,126, 18939). V. V.Krishnamurthy, J. Magn. Reson., Ser. A:, 1995, 114,88. G. Keglevich, K. Ujszaszy, A. Szoellosy, K. Ludanyi, and L. Toke, J. Organomet. Chem., 1996,516, 139. S . Samanta and N. K. Roy, Indian J. Chem., Sect B: Organic Chem. Incl. Med. Chem., 1996,35,489. K. Yamashita and T. Oshikawa, Jpn. Kokai Tokkyo Koho JP 08109189 A2, 1996 (Chem. Abstr., 1996,125,86 876). K. Yamashita and T. Oshikawa, Jpn. Kokai Tokkyo Koho JP 08109190 A2, 1996 (Chem. Abstr., 1996,125,86 877). A. Chaturvedi, R. K. Sharma, P. N. Nagar, and A. K. Rai, Phosphorus, Sulfur, Silicon Rel. El., 1996,112, 179. Y-G. Li, X-F.Zhu, Q. Huang, and J. Liu, Gaodeng Xuexiao Huaxue Xuebao (China), 1996,17, 1394 (Chem. Abstr., 1997,126,8 181). R. Lu, H. Yang, and Z. Shang, Phosphorus, Suyur, Silicon Rel. El., 1996, 108, 197. F. Lopez-Ortiz, E. Pelaez-Arango, and P. Gomez-Elipe, J. Magn. Reson., Ser. A., 1996,119,247. M. Briess and H, Pritzkow, 2.Anorg. Allg. Chem., 1996,622,858. M. D. Rudd, S. V.Lindeman, and S. Husebye, Acta. Chem. Scand, 1996,50,759. M. Kranz and S. E. Denmark, J. Org. Chem., 1995,60.5867. D. G. Gilheany, Chem. Rev., 1994,94,1339. M. Kranz, S. E. Denmark, K.A. Swiss and S . R. Wilson, J. Org. Chem., 1996,61. 8551. G. Jochem, F. Breitsameter, A. Schier, and A. Schmidpeter, Heteroat. Chem., 1996, 7,239. W. G. Bentrude ‘Conformational Studies of Six-Membered Ring Carbocycles and Heterocycles’;Ed. E. Juaristi, Publ. JCH 1995 pp 245-293. Y. Huang, A. M. Arif and W.G. Bentrude, J. Org. Chem., 1993,58,6253. Y . Huang, J. Yu and W.G. Bentrude, J. Org. Chem., 1995,60,4767.

356

OrganophosphorusChemistry

77.

Y. Huang, A. E. Sopchik, A. Arif and W. G. Bentrude, J. Am. Chem. SOC.,1993,

78. 79. 80.

Y. Huang and W. G. Bentrude, J. Am. Chem. SOC.,1995,117,4031. Z-H. Jiang, D. S. Argyropoulos, and A. Granata, Magn. Reson. Chem., 1995,33,375. A. Kers, I. Kers, A. Kraszewski, and J. Stawinski, Collect. Czech Chem. Commun.,

81. 82.

85.

L. Lassalle, S. Legoupy, and J-C. Guillemin, Organometallics,1996,15, 3466. I. S. Nizamov, G. G. Garifzyanova, and E. S. Batyeva, Izv. Akad. Nauk, Ser. Khim. (Russia), 1996,1,230 (Chem.Abstr., 1996,125,33 756). C-G. Xia, H-L. Song, and D-G. Li, Youji Huaxue (China), 1996, 16, 344 (Chem. Abstr., 1996,125, 301 078). K. Eichele, R. E. Wasylishen, J. M. Kessler, L. Solujic, and J. H. Nelson, Inorg. Chem., 1996,35,3904. R. Blachnik, U. Peukert, H-P. Baldus, and B. W. Tattershall, Z. Anorg. Allg. Chem.,

86. 87. 88.

H. Jancke, B. Costisella, and K. Jancke, Fresenius’ J. Anal. Chem., 1995,352,496. Y . Lin, Bopuxue Zazhi (China), 1996,13,365 (Chem. Abstr., 1996,125,221 987). T. A. Zyablikova and B. I. Buzykin, Zh. Obshch. Khim., 1996,66,470 (Chem. Abstr.,

89. 90. 91. 92.

M. M. Wienk, R. A. J. Janssen, and E. W. Meijer, J. Phys. Chem., 1995,99,9331. M. M. Wienk and R. A. J. Janssen, Chem. Commun., 1996,1919. M. Schmittel, J-P. Steffen, and A. Burghart, Chem. Commun., 1996,2349. I. I. Patsanovskii, P. Graezyk, Zh.R. Gulyaeva, M. Mikolajczyk, and E. A.Ishmaeva, Zh. Obshch. Khim., 1996,66,467 (Chem. Abstr., 1997,126, 18 950). C. Silvestru, R. Roesler, I. Haiduc, R. A. Toscano, and D. B. Sowerby, J. Organomet. Chem., 1996,515, 131. Ya.A. Dorfman, G. S. Polimbetova, and E.Zh. Aibasov, Zh. Obshch. Khim., 1996, 66,240 (Chem. Abstr., 1996,125,276 008). Kh.Sh. Karimov, A. B. Alovitdinov, G. A. Karieva, and M. V. Khalmukhamedova, Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. (Russia), 1996, 39, 21 (Chem.Abstr.,1996,125,276 006). A. Moezzi, M. M. Olmstead, D. C. Pestana, K. Ruhlandt-Senge, and P. P. Power, Main Group Chem. (USA), 1996,1, 197. P. A. Tanner and K-H. Leung, Appl. Spect., 1996,50,5. A. Gharbi, A. Jonini, and A. Durif, J. Solid State Chem., 1995, 114,42. M. Ghassernzadek, K. Harris, and K. Dehnicke, 2. Naturforsch., B: Chem.

115,4031.

1996,61, S246.

83. 84.

1996,622,958.

1997,126,8 219).

93. 94. 95. 96. 97. 98. 99.

Sci.,1996, 51, 1423. 100.

H. Vogt,D. Wulff-Molder, and M. Meisel, 2. Naturforsch., B: Chem. Sci., 1996, 51,

101. 102. 103. 104.

R. Pikl, C. Fickert, and W. Kiefer, Fresenius’ J. Anal. Chem., 1996,355,351. I. Hornyak, L. Kozma, and E. Brisching, Microchem. J., 1995,51, 187. S. A. Shamsi and N. D. Danielson, Chromatographia,1995,40,237. 0. Tissot, M. Gonygou, J-C. Daran, and G. G. A. Balavoine, J. Chem. SOC.,Chem. Commun., 1996,2287. N. Kuhn, R. Fawzi, M. Steimann, and J. Wiethoff, Chem. Ber., 1996,129,479. S . E. Johnson and C. B. Knobler, Phosphorus, Suyur, Silicon Rel. El., 1996,115, 115. M. R. St.J. Foreman, A. M. Z. Slawin, and J. D. Woollins, J. Chem. Soc., Chem.Commun., 1995,21,2217. Y. I. Blokhin, D. V. Gusev, V. K. Belsky, A. 1. Stash, and E. E. Nifantyev, Phosphorus, Sulfiu, Silicon Rel. El. , 1995,102, 143. C. Chuit, R. J. P. Corriu, P. Monforte, C. Reye, J-P. Declercq, and A. Dubourg, J. Organomet. Chem., 1996,511,171. H. P. Schroedel, G. Jochem, A. Schmidpeter, and H. Noeth, Angew. Chem. (Int. Ed Engl.), 1995,34,1853. E. N . Rasadkina, T. A. Batalova, V. K. Belsky, and E. E. Nifantyev, Zh. Obshch.Khim., 1996,66,1039 (Chem. Abstr., 1996,125,301 094).

1443.

105. 106. 107. 108. 109. 110. 111.

8: Physical Methods 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151.

357

V. I. Kal’chenko, Y. Lipkovskii, Y. A. Simonov, M. A. Vystotski, K. Suwinska, A. A. Dvovkin, V. U. Pivozhenko, I. F. Tsymbal, and L. N. Markovskii, Zh. Obshch. Khim., 1995,65, 1311 (Chem. Abstr., 1996,124,202 411). W. E. Krause, M. Parvez, K. B. Visscher, and H. R. Allcock, Inorg. Chem., 1996,35, 6337. Y. Huang, A. M. Arif, and W. G. Bentrude, Phosphorus, Sulfur, Silicon Rel. El., 1995,103,225. I. I. Patsanovskii, Zh.R. Gulyaeva, E. A. Ishmaeva, E. G. Yarkova, and K. M. Petnisevich, Zh. Org. Khim., 1995,31,1553 (Chem. Abstr., 1996,125,33 754). I. Petnehazy, G. Clermentis, Z. M. Jaszay, P. Toempe, and L. Tocke, J. Chem. Res. ( S ) , 1995,9,345. V. K. Moothe, S. French, and R. S. Balaban, Anal. Biochem., 1996,236,327. J. Li, J. Janata, and M. Josowicz, Electroanalysis, 1996,8, 778. M. M. Buzlanova, I. Karandi, andN. N. Godovikov, Zh. Anal. Khim. (Russ.), 1996, 51, 301 (Anal. Abstr., 1996,58,9D 158). D. Bouchard and C. W. Bale, Sensors and Actuators, B., 1995, 23,93. A. I. Suarez, J. Lin, and C. M. Thompson, Tetrahedron, 1996,52,6117. C. D. Reddy, M. S. Reddy, C. V. N. Rao, C. N. Raju, C. Das, and G. S. Reddy, Indian J. Heterocyl. Chem., 1995,5, 49. J. S. Rhee, H. M. Park, and Y. W. Er, J. Korean Chem. Soc., 1995,39,902. H. Song and F. Abramson, J. American Society for Mass Spectrometry, 1995,6,421. S . Jankowski and J. Rudzinski, Heteroat. Chem., 1996,7,369. X . P. Lee, T. Kumazawa, K. Sato, and 0. Suzuki, Chromatographia, 1996,42, 135. S . J. Lin, H. L. Wu, Y. H. Wen, and S. H. Chen, Anal. Lett., 1995,28, 1693. S . Goenechea and U. Raab, Chromatographia, 1995,41,610. R. Garcia-Repetto, I. Garrido, and M. Repetto, J. AOAC International, 1996, 79, 1423. M. A. Ngoh and R. Cullison, J. Agric. Food Chem., 1996,44,2686. A. E. Habboush, S. M. Farroha, and H. I. Khalaf, J. Chromatogr.,A . , 1995,696,257. M. D. David and J. N. Seiber, Anal. Chem., 1996,68,3038. R. Eisert and K. Levsen, Fresenius’ J. Anal. Chem., 1995,351, 555. V. Camel, M. Caude, and A. Tambute, J. Chromatogr. Sci., 1995,33, 123. W. M. Draper, J. Agric. Food Chem., 1995,43,2077. P. L. Wylie and K. Uchiyama, J. AOAC International, 1996,79,571. H. Gu, L. Zhou, G. Cai, and Y. Zhong, Sepu (China), 1996,14,41. G. Cai, H. Gu, L. Zhou, G. Qu, and Y. Zhong, Fenxi Huaxue (China), 1996,24,886 S. Lacorte, S. B. Lartiges, P. Garrigues, and D. Barcelo, Environ. Sci. Technol., 1995, 29,43 I. T. Okumura and Y. Nishikawa, J. Chromatogr., A . , 1995,709,319. M. Yagi and A. Ichihashi, Amagasaki-shiritsu Eisei Kenkyushoho (Japan), 1995,20, 39. S . B. Lartiges and P. Garrigues, Analysis, 1995,23,418. M. Morello, L. Previale, and P. Quaglino, J. Chromatogr., A., 1996,740,263. M. W. Sokolowski and M. Sliwakowski, Chem. Anal. (Warsaw), 1996,41,763. T. K. Choudhury, K. 0. Gerhardt, and T. P. Mawhinney, Environ. Science Technol., 1996,30,3259. R. L. Smith, A. Schweighofer, H. Keck, W. Kuchen, and H. I. Kenttamaa, J. Am. Chem. Soc., 1996,118,1408. J. Fillion, R. Hindle, M. Lacroix, and J. Selwyn, J. AOAC International, 1995, 78, 1252. R. Y. Gao, G. S.Yang, H. X.Shen, R. Y. Chen, Q. Dai, and Q. S. Wang, J. Liq. Chromatogr. Relat. Tech., 1996,19, 171. W. H. Pirkle, L. J. Brice, S. Caccamese, G. Principato, and S. Failla,J. Chromatogr., A., 1996,721,241. K. Erdmann, T.Mohan, and J. G. Verkade, Energy &Fuels, 1996,10,378. G. W . Schieffer, Instrum. Sci. Technol., 1995,23,255.

358 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164.

Organophosphorus Chemistry

D. J. Zhan, D. Herreno-Saenz, L. H. Chiu, L. S. VonTungeln, Y.S. Wu, J. Lewtas, and P. P. Fu, J. Chromatogr., A., 1995,710, 149. R. J. Mauthe, G. A. Marsch, and K. W. Turteltaub, J. Chromatogr., B: Biomedical Applications, 1996,679,91. C. Molina, P. Grasso, E. Benfenati, and D. Barcelo, J. Chromatogr., A., 1996, 737, 47. S. Lacorte and D. Barcelo, J. Chromatogr., A., 1995,712, 103. S. Lacorte and D. Barcelo, Anal. Chem., 1996,68,2464. G. G. Ivanova, A. A. Ivanov, and A. N. Kashin, Zh. Anal. Khim. (Russia), 1996,51, 616. H. Nagashima and K. Kuboyama, Bunseki Kagaku (Japan), 1996,45941. G. G. Spencer-Beach, A. C. Beach, and R. C. Gupta, J. Chromatogr., B: Biomedical Applications, 1996,677,265. J. Wang and 1. M. Warner, J, Chromatogr., A., 1995,711,297. B. Chankvetadze, G. Endresz, and G. Blaschke, J. Chromatogr., A., 1995,704,234 C. J. Shaw and C. E. Silverman, Chirality, 1996,8,84. B. Chankvetadze, G. Schulte, and G. Blaschke, J. Chromatogr., A., 1996,732, 183. V. V. Ovchinnikov, Zh. Obshch. Khim., 1996, 66, 463 (Chem. Abstr., 1997, 126, 8 218).

Author Index

In this index the number in parenthesis is the Chapter number of the citation and this isfollowed by the refirence number or numbers of the relevant citations within that Chapter. Abad, M.M. (1) 238 Abafemi, C.A. (1) 227 Abarghaz, M. (1) 220 Abbenhuis, H.C.L. (1) 29 Abd el Khalik, S. (1) 398 Abdel-Megid, M.(1) 228; (7) 43 Abdou, W.M. (1) 415 Abe, T. (1) 443 Abiko, A. (6) 75 About-Jaudet, E. (4) 164,242, 253,270,271,277; (6) 93-95 Abramson, F. (8) 124 Abreimova, R.R. (7) 35 Abushanab, E. (4) 145; (6) 108 Abu-Shanab, O.L. (7) 238 A d o , M. ( 5 ) 152 Acosta, J.L. (7) 268-270 Adachi, Y. (1) I8 Adam, W. ( I ) 107, 196 Adamiak, R W . ( 5 ) 168 Adams, C.J. ( 5 ) 167 Adani, F. (4) 263 Adibi, M.(1) 424 Aesa,M.C.(1)211,212 Akyan, N.B. (5) 252 Afon'kin, A.A. (7) 109 Afonso, C.A.M. (1) 226 Agarkov, A.Yu. (4) 112 Agasawara, M. (1) 261 Agbossou, F. (3) 95,98 Agrawal, S. (3) 67; ( 5 ) 67,69, 74-76, 108,135 Agzamov, T.A. (4) 149 A h , K.D. (7) 288 A h , K.H. (1) 21 A h , Y. ( 5 ) 175

Aibasov, E . 2 . (8) 94 Aibasova, S.M. (7) 35 Aime, S. (8) 16 Aitken, R.A. (6) 45,46 Akacha, A.B. (4) 245,248 Akbaeva, D.N. (7) 35 A k h t ~S. , (5) 173 Akiba, K. (2) 30 Akutsu, K. (1) 261 Aladzheva, I.M. (1) 353 Alahmad, S. (1) 556 Al-Badri, H.(4) 164,242,271; (6) 95 Albanese, D. (1) 403 Albcrti, M. (7) 133 Albinati, A. (1) 116, 165 Albus, S.(1) 501 Alcaraz, G. (1) 223; (7) 25, 166 Aldcr, R.W. (1) 154, 155 Alegria, S. (1) 371 Alcksiuk, 0. (4) 18 Aleshkova, M.M.(4) 1-3 Alessio, E. (1) 365 A i e w d , P.F. (4) 6 1 Alcxandcr, J.B. (1) 458 Alcxandcr, K.M. (4) 192 Alexandra, A.M.Z. (7) 200 Alexandrova, N.A. (4) 3 1 1 Al'fosov, V.A. (7) 27 Allcock, H.R (7) 87,88,92, 114, 132,209,210,215,219, 221-225,227,229,232,233,

239,240,247,249,25 1,255, 256,273,296,297; (8) 113 Allen, C.W. (7) 86, 103 Allen, D.W. (1) 412 359

Allman, S.L.( 5 ) 243,268 Almer, H. ( 5 ) 35 AI'Metluna, L.A. (4) 45,46 Alonso, RA. (1) 8 1 Alovitdinov, A.B. (4) 149; (8) 95 Al-Shali, S. (7) 114,297 Altmann, K.H. ( 5 ) 90 Altmann, S. (3) 65; (5) 178 Alvarez, C. (7) 197 Alvarez, R (6) 110 Alvarez-Gutiemz, J.M. (7) 39 Amanov, R.U. (7) 19 Arnato, M.E. (7) 90 Arnbrosio, A.A. (7) 249 Amrallah, A.H. (7) 83 An, D.-L. ( I ) 43 1,432 An, Y.Z. (5) 198 Andcrs, E. (4) 327; (6) 74; (8) 6 Andcrson, A.C. ( 5 ) 86,228 Andcrson, D.K. (4) 116 Andcrson, J.L. ( 5 ) 198 Andcrson, P.P. (7) 61, 159 Anderson, C. (1) 145 Andrei, G. ( 5 ) 30 Andrcws. I.P. (1) 187 Andnanov, A.K. (7) 25 1-254,256, 267 Andrus, A. (5) 85.87 Angelov, C.M. (7) 28,29 Angermaia, K. (1) 394; (8) 46 Anisimova, E.A. (4) 88,89 Anjeh, T.E.N. (6) 135 Antipin, M.Yu. (1) 338,353; (3) 37,40; (7) 19 Antipov, E.M.(7) 261,262 Antsypovich, S.I.( 5 ) 183

OrganophosphorusChemistry

360 Anuradha, K. (4)7,9,10,36;(8) 31 Anzai, S.(7) I12 Aoyarna, T.(6)136 Aparicio, D. (1) 334,336;(6)66, 67;(7)45 Aprna, K. (8)47 Arai, M. (5) 174 Arai, T.(4) 129 Arasasingham, R D . (4)70 Arbuzova, S.N.(1) 87, 1 19, 120, 350 Arcas, A. (1) 393 Arce,A.J. (1) 541 Arehart, K.R (7)284 Argyropulos, D.S.(8) 79 Arif, A.M. (8) 75,77,I I4 M i e n , A.E. (7)83 Ariknwa, Y.(1) 28 Armbnrst, R. (1) 538 Arnason, I. (1) 448 Arnaud-Neu, F. (1) 320,321 Amdf P. (1) 251 Arnold, J.RP. (5) 167 Arnold, L.J. (5) 189 Arnold, R.J. (5)257 Artyushin, 0.1,(1) 338 Asai, K.(3) 15 Asakura, C.(1) 425 Asakura, K.(1) 188 Asam, A. (1) 58 Asghari, J. (7)21 1 Ashby, E.C.(1) 83 Ashe, A.J. (1) 556 Ashikawa, T.(1) 310 Ashman, C.(5)3 1 Aspinall, H.C.(1) 37 Asseline, U.(5) 163,191 Assmann, 8.(1) 394;(8)46 Atlan, S.(I) 102 Atton, J.G. (1) 174 Attwaia, M. (7)249 Atwood, D.A. (1) 93 Aubertin, A.-M. (3)60;(5)3 Aubuchon, S.R(1) 96 Augustyns, K. (4) 191,201 Austin, R.E. (5) 25 Avendaiio, C. (6) 125 Avenf A.G. (1) 65 Averin, A.D. (1) 472,473;(3) 102; (7)30-34 Avis, J.M. (5) 229 Avis, M.W. (7)76, 187, 188 Aw, B.-H. (1) 266 Awadallah, R M . (7) 83 Awano, H.( 5 ) 8 Axenrod, T. (7) 104

Ayed, N. (1) 335; (4)248 Aymand, C. (4)208 Ayupova, E.I. (1) 242 Azhayev, A. (3) 61,74;(5) 64 AmM, F. (5) 156 Baan,G. (1)211,212 Baba, A. (1) 369 Baba, G. (1) 130 Baban, J.A. (4)125 Babu, RP.K. (8)47 Bac, A. (7)226 Baccar, B. (1) 335; (4)245,248 Baceiredo, A. (1) 223,272,273, 522,542;(3) 1 11; (6)7;(7)25, 165,166;(8)54 Bachrach, S.M.(I) 450,452,553; (8) 4 Baczko, K.(4)21 1 Bader, A. (1) 132 Baek, H.(7)213,214 Bahri, H. (1) 195 Bahrmann, H.(1) 7 Bai, J. (5) 242 Baik, H.(7)248 Baillct, S.(5) 164 Badly, T.(4) 186;(8) 52 Baimashov, B.A. (4)165 Bajorat, B. (6)48 Bakaoui, L.(7) 197 Bakos, J. (1) 42 Bakshi, P.K.(1) 402.5 12 Balaban, R.S. (8) 117 Balas. L.(6)100 Balavoine, G.G.A. (1) 30;(8) 104 Balcmski, P. (4)284 Baldino, C.M. (6)42 Baldus, H.-P. (8) 85 Baldwin, l.C.(4)261;(6)71 Baldwin, R.A. (1) 97 Balc, C.W. (8) 120 Balueva, AS. (1) 176,177,242, 289 Balzarini, J. (5) 1,2,5,30,32,33 Bandini, E.(3) 14;(4)133,134 Bank, J. (1) 70 Banks, M.A. (1) 99 Bannister, R (I) 187 Banno, T.(7)85 Bannworlh, W.(3) 65;(4)32;(5) 112,178 Banoub, J. (5)25 1 Baraniak, J. (5) 48 Baranov, G.M. (4)264 Barany, G.(3) 20;(5) 96 Barbaro, P. (1) 163

Barber, I. (5) 130, 131 Barbosa, J. (6)121 BWCC~O, D. (8) 139, 154-156 Bardaji, M. (1) 140 Barion, D.(1) 471 Barkallah, S.(2)18;(4)245;(6) 82 Barluenga, J. (6)6;(7)171,172 Barnckow, F.(5)73 B m , C.L.(3) 29;(7)66,187 Barnes, N.J. (4)152 Bmans, Y.(I) 305 Bany, J.P. (5) 235,271 Barsky, D.(5) 220 Barlh, A. (1) 57 Barthel-Rosa, L.P.(1) 244 Bartoli, G.(6)60 Barton, J.K. (5) 212 Barullin, A.A. (3)39 Barycki, J. (4) 179 Bascunan, M. (1) 371 Bashkin, J.K. (5) 195 Basoli, C. (1) 80 Bassmann, H. (1) 509 Bassoul, P. (1) 305 Bassowa, A. ( I ) 72 Basu, S.(5) 190 Batalova, T.A. (8) 1 1 1 Bats, J.W. (4)137 Batsanov, A.S. (1) 387;(4)155; (6)129 Batyeva, E.S. (4)45-48;(8)82 Bau, R (4)167 Baudlcr. M. (1) 168 Baucr, A. (I) 74;(7)82 Bauer, W.(1) 499;(7)192;(8) 8 Baulin, V.E. (1) 31 1 Baumann, P.A. (3)4,s;(4)218, 219 Baumann, W.(1) 59.25 1 Bautista, D.(1) 393 Baxter, A.D. (5) 36 Baylis, E.K. (4)220 Beach, A.C. (8) 159 Beachley, O.T. (I) 99 Beak,P.(l) 193 Beaucage, S.L.(5)133,134 Beck, T.A. (5) 189 Becker, A.R (3) 41 Becker, C.H. (5)254 Becker, G. (1) 71,465 Bccker, P. (1) 537;(6) 17 Becketl, R.P. (4)261;(6)71 Beckmann, H. (1) 198;(4)3 16, 320 Bedel, C.(1) 577;(7)168 Bedford, C.D.(7)104

Author Index Bedford, RB.(1) 460 Bednarski, K. (5) 31 Becr, P.D. (1) 222 Begeman, C.(8)1 Be&, J.-P. (4) 105; (6)98 Behr, J.P. (5) 164 Behrens, C. (5) 202 Behringer, K.D.(1) 146,147 Beigelman, L. (5) 137, 197 Beitti-Verrando, S.(4) 163 Bekker, A.R (3) 32,46,47;(4) 318;(8)45 Bclaj, F.(7) 170 Bcletskaya, I.P. (1) 55, 167, 178, 290,472,473;(3) 102;(4) 112, 260;(7)30-34 Bell, K.E. (1) 215 Beller, M.(1) 253,254 Bellon,L.(5) 120 Bellucci, G. (6)23 Bel'skii, V.K. (2)5; (3)35,36,38, 46;(4)235,306,318,322;(8) 45,108,111 Belyaev, A. (4)20 I Ben Akacha, A. (1) 335 Ben-Bari, M. (4)208 Benelmoudeni, M.(1) 322 Bdenati, E. (8)154 Bengourina, C. (3) 34 Benke, P. (1) 412 h e r , S.A. (5) 54, 128 Bennett, D.W.(1) 175;(4)240, 301,302 Bentrude, W.G. (2)26;(3) 45;(4) 329;(8) 74-78,114 Berchadsky, Y. (1) 264 Berens, C. (5) 200 B e r n , U.(1) 8 Berestovitskaya, V.M. (4)264 Berg, T. (I) 14 Berger, D.J. (1) 564 Berghofcr, J. (1) 9 Berghoff, U.(5) 166 Bergin, C.(3) 6; (6) 103 Bergmann, F. (5) 1 12 Berg& B.J. (5)98 Bergslriisser, U.(I) 480,484, 486-489,538,561 Bcrkcssel, A. (4) 3 1 Berkova, G.A. (4)264 Berkowitz, D.B.(4) 121;(6)84 Berlin, K.D. (4)5,7,9-11.36 Berlin, Y.A. (3)75,79;(5) 201 Berman, H.M. (5)232 Bernardinclli, G.(1) 439 Bemasconi, R. (3) 5; (4)218 Bern, P. (6)47

361 Berressem, R (5) 162 Bettani, R (6)38 Bertrand, G. (1) 53,223,272,273, 293,522,538,542;(3)I 1 I; (6) 7,9;(7)25, 165-167;(8)54 Bespalova, I.B. (3) 47 Besson, T. (1) 199 Bestmann, H.J. (1) 422;(2)7;(6) 11,44 Beugelmans, R (1) 559,560; (4)

Blaszczyk, J. (4)183,305,317;(5) 93 Blaton, N. (4) 201 Blcchert, S.(4)262 Bloemhoff. W.(3) 88 Blokhin, Yu.1. (3) 35.37.49; (4) 235;(8)108 Blonski, C.(4)144 Blumcl, J. (I) 146,147 Blumenfeld, M.(5) 183 114 Boal, J.H. (5) 133, 134 Bezuglov, V. (6) 1 17 Bochkova, RI. (2)6 Bochmann, M.(7)207 Bhandaru, S.(6) 133 Bhatia, D.(3) 73;(5) 203 Bocskei, 2.(I) 575; (4)239 Bhatia, P.V.K. (I) 38 1 Boczkowska, M. (5) 92 Bhattacharyya, P. (I) 377,379;(7) Boduszck. B. (4) 189 Btihmer, V. (1) 321 195,200,204 Bhawal, B.M. (7)40 Boere, R.T. (7)191 Bhongle, N.N. (5) 18,63 Bdmer,A.(I) 11.45 Bi, G.X. (5) 160 Boese, R (1) 277 Biala, E. (5) 168 Bogacki, R (5) 161 Biali, S.E.(4) 18 Bogdan, M. (7)72 Bianchini, C. (1) 86 Bogge, H.(1) 405 Biancotto, G.(3) 54 Boggon, T.J. (5) 23 1 Bickelhaupt, F. (1) 28 1,459,566, Bohsako, A. (1) 425 570,571 Boisdon, M.T. (4)245 Bidaine, A. (5) 200 Bojin, M.L. (2)18; (6)82 Biedron, T. (1) 426 Bolbach, G. (5) 262 Bieger, K. (1) 324;(6)6;(7) 167, Bollmark, M.(5) 40 Bonadies, F.(6)78 171, 172;(8)29 Bigam, G. (7)186 Bonaplata, E.(1) 129 Bigey, P. (5) 193 Bondarenko, N.A. (1) 3I3 Bigner, D.D.(5) 220 Bonged, D.(1) 88 Billeter, M. (3) 65;(5) 178 Bongini, A. (3) 13; (4) 133,204 Binder, H. (1) 76,88,89,436,529 B O M C t - h l p O t l , D.(4)105; (6)98 Binet, L.(1) 387;(6) 129 Borch, R.F. (5) 7 Binger, P. (1) 501,502,506 Bordachcv, A.A. (1) 167 Bordwell, F.G. (1) 409;(6)2 Birchhirschfeld, E.(5) 72 Birkel, M.(1) 197 Borisenko, A.A. (1) 472,473;(3) 102;(7)31-34 Birse, E.F.(I) 342;(6)64 Biryukov, S.V. (4)153 Borisevich, A.N. (8)12 Bisagni, E. (5) 206,207 Borisova, I.V. (1) 392 Bissessur, R (7)24I, 242 Borloo, M.(4)191,201 Borncr, A. (1) 59, 139;(3) 91 Bitterer, F.(1) 153 Bittiger, H.(3) 4,5;(4)218,219 Born,s.(I) 45 Biu, J. (4)63 Bortoletto, M.H. ( I ) 122 Boschenok, J. (5) 269 Bizdena, E. (5) 21 Bjamason, A. (1) 448 Bosschcr, G. (7) 123,124 Blachnik, R (8)85 Bolala, Zh.k(4)264 Blackbum, G.M. (5)48 Bolhncr, B. (5) 270 Blades, K. (4)127, 161 Bott, S.G. (1) 250 Blair, I.A. (6) I19 Bdta, M. (8) 16 Blais, J.C. (5) 262 Bdleghi, C. (1) 80 Bdtomlcy, L.A. (6)116 Blanot, D.(4)221 Blaschke, G. (8)161,163 Bouchard, D.(8)120 Blasko, A. (1) 348;(4)69,70 Bougauchi, M. (4)129 Bouhadir, G.(1) 293;(7)167 Blass, B.E. (6)120

Organophosphorus Chemistty

362

Boukherroub, R. (1) 36,288 Boukraa, M. (1) 335; (4) 245,248 Boulaajaj, S. (4) 128 Bourguignon, J.-J. (1) 220 Bourne, S. (4) 298 Bouvier, J.-P. (4) I50 Boyd, E.A. (3) 10, 12; (4) 113 Boyd, M.E.K. (3) 12; (4) 113 Boys, D. (1) 371 Bozhko, O.K. (1) 3 13 Brack, A. (5) 191 Bradley, J.C. (5) 77 Braga, A.L. (6) 140 Brain, P.T. (1) 260 Brand, A. (1) 307,347 Brandsma, L. (1) 17, 1 19 Brandt, K.(7) 1 16- 1 18 Branea, M. (8) 18 Brash, A.R (6) 119 Braun, A. (5) 246 Braun, R (7) 63 Braunstein, P. ( I ) 118; (7) 185 Bravic, G. (1) 305 Brawn, D.G. (4) 172 Bray, A.M. ( I ) 204 Brem, T.L. ( I ) 526,527 Breit, B. (1) 234,490; (8) 2 1 Breitsameter, F. (8) 73 Brern, H. (7) 246 Brenchlcy, G. (1) 189 Brennan, D. (7) 132 Brennan, T. (5) 8 1 Breton, F. (1) 322 B r e w , E. (4) 254 Breuker, K. (5) 253 Breunig, H.J. (7) 199 Brice, L.J. (8) 149 Bricklebank, N. (I) 180; (3) 2 1 Briess, M. (8) 68 Brimfield, A. (2) 9 Brisbois, R.G. (4) 172; (6) 96 Brisching, E. (8) 102 Britt, P.F.(5) 258 Broger, E.A. (1) 157 Brooks, D.A. (6) 41 Broschk, B. (1) 494 Brossmer, C. ( I ) 253,254 Brossmer, R. (5) 10 Brovarets. V.S. ( I ) 389-391 Brown, D.G. (6) 96 Brown, D.M. (5) 56,157 Brown, J.M.(1) 8,125 Brown, M.A. (1) 48 Brown, P.W. (7) 240 Brown, T. (5) 23 1 Browning, C.S.(4) 304; (7) 196 Broyde, S.(5) 223

Bruch, M.D.(4) 28 1 Bruckmann, J. (1) 502 Brueck, A. (4) 292 Bruenger, E. (5) 260 Brugger, F. (3) 4; (4) 2 19 Bruice, T.C. (4) 69.70 Bruneau,C. (1)315 Brunel, J.M.(3) 90 Bruncl, Y.(6) 36 Brunner, H. (1) 9.35 Bryan, C.D. (7) 134 Bryce, M.R (1) 387; (6) 129 Bubenheim, W. (1) 404 Buchanan, M.V. (5) 258,259,266 Buchardt, 0.(5) 1 15, 116, 118, 202 Buchwald, S.(I) 438 Budesinsky, M. (5) 49 Budnikova, Yu.G. (4) 4 Budzichowski, T.A. (1) 496 Buchner, M. (1) 59; (3) 92 Buhling, A. (1) 62 Bujacz, G.D. ( I ) 355 Bunton, C.A. (1) 348 Buono, G. (4) 142 Bur, D. (3) 65; (5) 178 Burckhardt, U. (I) 29 Burford, N. (1) 5 12 Burgada, R (4) 186; (8) 52 Burghart, A. (8) 91 Burilov, A.R. (3) 39 Burini, A. (4) 106 Burkart, W. (1) 179 Burke, T.R. (4) 35,213 Burkhardt, D.M. (5) I5 1 Burmistrov, S.Y.(3) 41,48 Burns, J.A. ( I ) 98 Burrow, D.H. (4) 304 Burrows, C.J.(5) 226 Burton, D.J. (4) 122 Burton, S.D. (7) 285 Butenschiin, H.(1) 497 Butin, B.M. (1) 236,357 Butler, 1.R (I) 161 Buyevich. A.V. (1) 249 Buzlanova, M.M. (8) 119 Buzykin, B.I. (4) 294,303; (8) 41, 88 Bwcmbya, G.C. (7) 207 Bychkov, V.T. (2) 6 Byers, J.H. (4) 283 Bykhovskaya, O.V. (1) 353 Bysotskii, M.A. (4) 16 Cabcl, D. (1) 202 Cabras, M.A. ( I ) 80

Caccamese, S. (8) 149 Cacchi, S. (4) 106 Cahard,D. (5) 1,2 Cai, G. (8) 137, 138 Caldwell, C.G. (4) 99 Caliceti, P.(7) 243 Caliman, V. ( I ) 552,553 Callahan, J.H. (5) 265 Camel, V. (8) 134 Camellini, M.T. (1) 393 Camcrini, R (3) 13; (4) 204 Cameron, C.G. (7) 221,233,255 Cameron, T.S. (1) 402,5 12 Camha&, A.-M. (1) 140,297; (4) 234; (7) 22,120 Campagne, J.-M. (4) 25 1 Campbell, C.N. (5) 199 Campion, B. (7) 107 Campli, C.D.(6) 78 Campos, J. (1) 183 Campos, K.R (1) 15 1; (6) 56 Canac, Y.(1) 522,542 Cano, A. ( I ) 1 1 1 Cantor, C.R. (5) 246,264 Cao, R (8) 5 1 Capcrelli, C.A. (5) 11 Capparelli, M.V. (1) 54 1 Caprita, A. (4) 119 Cardellicchio, C. (6) 80 Cardin. C.J. (1) 11 1 Carmichacl, D. (I) 554,568 Carpentier, J.F.(3) 95,98 Cam, N. (1) 505 Carre, F. (4) 3 10 Carriedo, G.A. (7) 113, 137,138 Carson, D.A. (5) 24 Carty, A.J. (1) 530 Caruthcrs, M.H. (3) 82; (5) 42,99; (7) 21 Casanove, M.-J. (1) 140 Casida, J.E. (4) 243 Cassagne, M. (1) 385 Cahlmo, V.J. (1) 244,550 Caude, M. (8) 134 Cauzzi, D. (1) 373,374 Cavell, RG. (2) 4,29; (7) 28,29, 67,77, 186; (8) 55 Cca-Olivares. R (1) 378; (7) 201, 206,294 Ccch, D. (5) 166 Cen, W. (4) 214 Cenac, N. (1) 138,245; (7) 79 Ccreghetti, M. (1) 157 Chaikovskaya, A.A. (1) 283 Chaires, J.B. (5) 209 Choix, C. (5) 135 Chakhchcva, O.G. (3) 19

Author Index Chakhmakhcheva, O.G. (5) 95 Chakroune, S. (1) 387; (6) 129 Chalier, F. (1) 264 Challet, S. (1) 105 Chalton, M.A. (1) 387; (6) 129 Chan, K.S. (1) 152 Chan, W.C. (3) 10 Chandrasekaran, A. (2) 16; (5) 111 Chandrasckhar, V.(7) 105, 134, 135; (8) 53

Chane-Ching, K. (1) 305 Chang, B.C. (4) 99 Chang, C.-W.T. (1) 49 Chang, J.Y. (7) 127 Chang, L.Y. (5) 268 Chang, Y.-T. (4) 23 Chankvetadze, B. (8) 161,163 Chapleur, Y. (6) 35 Chapyshev, S.V.(1) 561 Charette, A.B. (1) 209 C h m e , M.-Th. (1) 322 Chamier, C. (1) 573 Chambala, R (5) 147 Chasseau, D. (I) 305 Chastrette, F. (4) 291 Chatman, K. (5) 270 Chahuvedi, A. (8) 64 Chaudhuri, N.C. (5) 179 Chaudrct, B.(1) 140 Chauhan, M. (1) 262 Chautemps, P. (6) 138 Chbani, M. (1) 559,560; (4) 114 Chelucci, G. (1) 80 Chcmla, F. (6) 53 Chen, C.H. (5) 198,243,268 Chen, C.S. (1) 22 1 Chen, C.-T. (4) 258; (6) 91 Chen, J. (3) 77 C h , J.K. (5) 1 10 Chen, Q.-Y. (4) 120 Chcn, R (4) 3 15 Chen, RY. (8) 148 Chen, S. (4) 222,224 Chen, S.F.(7) 128 Chen, S.H. (8) 127 Chen, W.B. (4) 71 Chen, Y.M. (5) 153,155 Chmg, C.-H.(1) 171,172 Cheng, D. (4) 146 Cheng, D.L. (5) 22 Cheng, X.H.(5) 272,273 Chen-Yang, Y.W. (7) 128,231 Cherkasov, R.A. (1) 563; (4) 282; (8) 28

Chern, J.W. (I) 221 Chern, RT. (7) 236 Chernega, A.N. (1) 247,391,435;

3 63 (2) 10;(7) 5; (8) 5 Cherney, R.J. (1) 208 Chernykh, L.A. (7) 163 Chemyshev, E.A. (7) 163 Chesney, A. (1) 387; (6) 129 Chiacchiera, S.M. (1) 224; (7) 14 Chiappe, C. (6) 23 Chidambaram, N.(5) 23 Chicn, T.C. (1) 221 Chin, Y.S. (7) 128 Chisholm, M.H. (1) 496 Chistokletov, V.N. (4) 246 Chiu, L.H. (8) 152 Chivers, T. (7) 65, 173, 174 Chmutova, G.A. (8) 10 Cho, C.-G. (6) 135 Cho, C.-H. (7) 220 Cho, C.-W. (1) 2 1 Cho, H.G. (1) 124 Cho, Y. (7) 214 Cho, Y.H. (7) 213 C h , S.-H. (7) 147 Chottard, J.C. (5) 262 Choudhwy, T.K.(8) 145 Christensen, L.M. (5) 98 Christian, N.P. (5) 257 Chuburu, F. (4) 77 Chuiko, A.L. (8) 12 Chuit, C. (1) 262,263; (4) 310; (8) 109

Chung, C.N. (5) 243,268 Chug, S.-K. (4) 23,25, 188 Cicchi, S. (1) 347 Cicslnk, J. (5) 4 1 Cipolln, L. (4) 2 10 Cisarova, I. (1) 160 Claridge, T.D.W. (I) 125 Clayden, J. (1) 327,330; (6) 5 1,62 Clcary, D.G. (5) 25 Clement, R. (7) 286 Clcrmentis, G. (8) 116 Cloke, F.G.N. (1) 555 Clowney, L. (5) 232 Clyburne, J.A.C. (1) 492 Coats, S.J. (6) 42 Cockerill, G.S.(4) 127 Coggio, W.D. (7) 273 Cohcn, S. (7) 25 1,256 Colby, S.M. (5) 257 Cole, A.G. (4) 65,66 Cole, D.L. (5) 97,252 Coleman, R S . (5) 182 Coles, S.J. (1) 156; (7) 207 Collignon,N. (4) 100,126, 164, 242,253,270,271,277; 93-95 Collin, J. (1) 303

(6) 72,

Colman, S.G. (5) 3 1 Colvin, M.E.(5) 220 Colvin, O.M.(5) 220 Combes, C. (7) 100 Combret, 3.-C. (4) 164 Comenges, G. (1) 138 Commedord, J.C. (4) 172; (6) 96 Condieu, C. (2) 9 Connolly, B.A. (5) 23 1 Contreras, R.( I ) 371,372 Convery, M.A. (1) 1 I I Cook, A.F. (5) 107 Cooper, D.L. ( I ) 258 Cooper, H.R (6) 45 Corain, B. (1) 363 Corbcl, B. (4) 158 Corbelin, S. (1) 474; (3) 99 Corda, L. (7) 1 11 Cordes, A.W. (7) 134, 135 Cordonnier, G. (3) 34 Corrigan, J.F. (1) 530 Corriy R.J.P.(1) 262,263; (4) 310; (8) 109

Cotvaja, C. (1) 363 Cosstick, R. (5) 36 Costa, J. (4) 25 1 Costisclla, 8. (4) 325; (8) 86 C6tc, B. (1) 209 Cottam. H.B. (5) 24 Cotter, RJ. (5) 246,264 Couch, K.M. (4) 9,36 Coull, J.M. (5) 138 Courct, c. (1) 433 Coutrot, P. (4) 159; (6) 100, 107 Coward, J.K. (4) 222 Cowart, M.(4) 192 Cowley, A.H. (1) 93,474; (3) 99 Cox, P.J. (1) 48 cozar, 0. (7) 9 Crabtree, R.H. (I) 345 Cramcr, F. (3) 84 Cramer, R (5) 247 Crameri, Y.(I) 157 Crasnier, F. (7) 106,108 Cremex, S.E. (4) 240,300-302, 323,324

Crich, D. (4) 5 1 Cristau, H.-J. (1) 326,385,413; (4) 197.23 1; (6) 40; (7) 23,37, 100 Cross, D.J. (6) 55 Cross, RJ. (I) 359 Cucnca, T. (1) 1 11 Culea, M.(7) 9,72 Culeddu, N. (8) 18 Cullen, W.R (I) 161 Cullison, R (8) 130

364 de Jong, J.C.(1) 63 de Kanter, F.J.J. (1) 566 Dekoven, B.M.(7) 142,147 delaCuesta,E.(1)461 Delaney, W. (5) 107 Delang, RJ. (1) 17 Dabkowski, W. (3)84,85;(4)54; de Lange, W.G.J. (3) 3 1 de Lera, A.-R (6) 110 (5) 39 Dahan, F.(1) 223,245,272;(6)7; Delogu, G.(7)1 1 1 de 10s Santos, J.M. (1) 334,336; (7)25,167 (6)66,67;(7)45 Dahl, 0.(3)2;( 5 ) 101,202 De Lucchi, 0.(1) 543 Dahlenberg,L. (1) 34,133 Delumlqrwoodyear, T.( 5 ) 199 Dahmen, F.Y. (1) 31 Dai, H.-P.(1) 56 Dembitlski,R (4)305 De Meester, 1. (4)201 Dai, Q. (8) 148 Demcsmaeker, A. ( 5 ) 90,91 Daily, W.J. (5) 189 Dcmic, S.(4) 175 Dallemer, F.(1) 303 Dcmik, N.N.(4)112,260 Dalluge, J.J. ( 5 ) 222 Demike, J.K. 44) 198 Damha, M.J. (5) 122 Demir, A S . (4) 175 Dance, 1. (1) 410 WS, J.-M. (1) 130 Danel, K.(5) 127 Denise, B. (7)197 Daniels, J. (1) 408 Denmark, S.E. (4)258,259,275, Danielson, N.D. (8) 103 278;(6)73,89,91,92;(8) 9, Daniher, A.T. ( 5 ) 195 70,72 Daren, J.-C. (7)197;(8) 104 Darcel, C. (1) 315 De Ranter, c.(4)201 Deriesemeyer,L.(1) 168 Das, C.(4)326;(8) 122 Deroussent, A. ( 5 ) 255 Daubendiek,S.L. (5) 80,89 Demc, S.(7)191 Dave, P.R (7) 104 Dervan,P.B.( 5 ) 210 David, M.-A. (1) 457 Desanctis. Y. (I) 541 David, M.D. (8) 132 Deschamps,B.(1) 539,546 David, S.S.( 5 ) 150, 15 1 Deshmukh, A.RA.S. (7)40 Davidson, M.G. (1) 1 13 Deshpande, A.K. (1) 83 Davies, D.B. (7) 116-118 Desmde, D. (6)3 1 Davis, D.R (5)222 Davis, R W . (5) 81 Desponds, 0.(1) 4.5 Deuklly, B. (6)49 Davis, W.M. (7)81 Dcubzer, B.(7)59.63 Day, RO.(2)16;(8)53 Deuwcr, D.L. (4)116 Deadman,J. (4) 125 Devaquct, E.(3) 93 Decavallas, 0.(4)200 Devitt, P.G. (3) 89;(4) 130,131 DeCian, A. (1) 118,319;(7)52 Devlin, T.(3)67;( 5 ) 67,74-76, Decken, A. (1) 474;(3)99 108 Dcclcrcq, E.(5) 1,2,5,30,32,33, Dcvocelle, M. (3)95,98 152 Dewintcr, H.( 5 ) 142 Declerq, J.P. (1) 262,263;(8) Dcwynter, G. (4)208 109 . Dtz,I. (7)129,130 Dccatc, B.L. (5) 181 Diaz,M.R (7) 137 -M. (7)7 I)ldr,S.(1) 476,477;(3) 101;(6) Be Dianous, P.(1) 562 15,16 Deeming,A.J. (1) 54 I Diederich, F. (4)13 &Forrest, J.M. (4)226 D i m U.(5) 113,114 Dehnidrc, K. (1) 401; (6) 18; (7) Diefenbach, U.(7) 136,2% 64,69-71,73-75,176-182, Diel, P.J. (3)5; (4) 176,218;(8) 295;(8)99 30 Deicke, P.(6)25 Dieleman,c.(1) 319 Deiio, L.I.(4)264 Diemann, E.(1) 405 DeJacger, R (7)129,130,234

Cummins, C.C. (7)8 1 Cupertino,D. (7)203,205 Curci, M.(4)42,74 Cushman, M.(3)77

OrganophosphorusChemistry Dierdorf,D. (7)89 betz, T.(4)52 Di Grandi,M.J. (1) 217 Dilling, W.L.(7)141 Dillon, K.B.(I) 437;(3) 103 Ding, D.Y. (5) 11 1 Ding, H.(1) 42,129 Ding, M.W. (1) 388 Ding, Y. (6)116 Dircnto, A. (5) 83 Dim, P. (1) 16 Dixit, D.M. (5) 3 1

Dixneuf,P.H.(1)315 Dixon, N.E.( 5 ) 216 Dizitre, R (4) 1 1 1, 163 hnitrichcnko, M.Yu. (4)286;(7) 169 Dmitricv, V.I.(1) 87 Dobbat, E.(I) 438 Doblcr, c.(3) 97 Doboszewski, B. (5) 142 Dodge, J.A. (1) 207 Dodin-carnot,v.(4)74 Dogadina, A.V. (4)90 Doi, T.(5) 126 Doktycz, M.J. ( 5 ) 266 Ddruchaev, A S . (4)303;(8) 41 Dolhainc, H.(7)91 Domalewski, W. (7)6 Domb, A.J. (7)246 Donaldson, W.A. (1) 175 Dong, D. (1) 322 Dong,Q.(5) 220 Dong, Y.(1) 362 Donnadieu, B.(1) 54,245 Dwkikh, V.I. (4)286;(7)169 Dore,A. (1) 543 Dorfman, Ya.A. (1) 121;(4)1-3; (7)35;(8) 94 Downprd,A.J. (3)8; (4)3 13 Downs, A.J. (1) 260 Doid, J.-F. (1) 320,321,326 Drobowitz, J. (4) 183 Dr& B.S.(1) 389-391,420,421; (6)39 Driiger, M. (1) 162 Drago, RS. (1) 255,257 Drakc, J.E. (7)202 Dransfeld, A. (1) 89 Draper, W.M.(8) 135 Dreschtr, M. (4) 139 Dreval, V.E.(7)259,260 Drew, M.6.B. (1) 265 Dries. M. (1) 39,78,100, 467-469 Drostc, C.A. (1) 175 D'Sa, RA. (2)27;(3) 16

Author Index Duan, Z. (2) 28 Dubau-Assibat, N. (8) 54 Dubois, F. (5) 253 Dubois, P.(6) 13 I Dubourg, A. (1) 262,263; (8) 109 Dubreuil, D. (4) 27 Ducharme, Y.(5) 53 Dudley, G.K. (7) 2 19 Duesler, E.N. (1) 306,515 du Mont, W.W. (1) 237,287 Duncan, G.D. (4) 147 Duncan, J.B. (7) 285 Dunina, V.V. (1) 248,249

Durand, T.(6) 1 17 Dureue, P.L. (4) 99 Durif, A. (8) 98 Durig, J.R (1) 301 Duygulu, M. (7) 238 Dvorakova, H.(5) 29,30 Dvovkin, A.A. (8) 112 Dwyer, B.P. (5) 189 Dyachenko, V.I. (4) 322 Dybowski, P. (4) 72,73 Dyer, P.(I) 272,273; (3) 111; (6) 7

Earnshaw, D.J.(5) 36 Earp, B.E.(5) 86,228 Eason, RG. (5) 151 Easterfield, H.J. (4) 127 Ebisawa, F. (7) 149 kkert, C. (1) 133 Ecksttin, F. (5) 47 Edmundson, RS. (4) 86,87 Edwards, A.J. (1) 113 Edwards, M. (7) 173 Edwards, P.G. (1) 103,156 Efmov. V.A. (3) 19,86; (5) 95 Eguer-Sicber, C. (1) 422; (2) 7; (6) 11

Egholm, M. (5) 202 Egli, M. (5) 54,230 Eguchi, S.(6) 122, 123; (7) 41,47 Ehleiter, Y.(1) 277 Eichle, K. (1) 530,550,55 1; (8) 84 Eida, K. (3) 57; (5) 68 Eicknhammer, G.(4) 140 Eigenberer, G.(7) 286 Eisenhardt, S.(3) 83 Eisert, R (8) 133 Eisswein, B. (7) 49 Eklund, A. (1) 134 El A d , K. (7) 23 El-Amin, S.F. (7) 249 Eldin, N.K.(7) 17 Eldmp, A.B. (5) 101

365

El Essawi, M. (1) 398 Elgendy, S.(4) 125 Elgcrsma, J.W. (1) 62 Eliscenkov, V.N. (4) 53 Ekhoshnich, Y.O.(1)415 Ellmann, 1. (1) 499; (7) 26, 192; (8) 8

Ellington, A.D. (5) 177,257 Ellis, D.D. (1) 154, 155 Elms, F.M. (1) 95 Elschenbroich, C. (1) 556 Elsevier, C.J.(7) 76, 187-189 EI-Sh-, H.M. (1) 228; (7) 43 Emayan, K. (1) 199 Enders, D. (I) 14 Endo, M.(5) 174 Endova, M.(5) 49 Endresz, G. (8) 161 Engel, J. (2) 24; (8) 38 Engelhardt, U. (I) 306 Engcls, J.W. (3) 83; (5) 162,247

Er, Y.W.(8) 123 Erabi, T. (1) 233,354 Erdmann, K. (8) 150 Ergashov, M.Y.(3) 37 Ergiidcn, J.-K. (I) 333; (6) 65 Eritja, R. (5) 152, 156 Erker, G. (1) 506; (6) 20.47 Ermolaeva, L.V. (1) SO8 Emst, A. (3) 93 Emst, L. (1) 493 Emstring, J.M. (7)187 Erokhina, E.V. (4) 91 Enhamov, K.B. (1) 236 Eschbach, F. (7) 274 Escude, C.(5) 206,207 Escudie, J. (1) 433 Espinosa, A. (1) 183 Espinosa-Perez, G. (1) 378; (7) 201,206

E t e ~ ~ a d - M ~ g h aG. d a(1) ~ ~36 ~, Etridge, S.K. (1) 187 Evans, D.A. (1) 151; (6) 56 Evans, S.A., Jr. (2) 18; (4) 279; (6) 82

Eversole, RR (4) 99 Evin, 0.0.(4) 175 Fabbri, D. (1) 543 Fabrc, J.M. (1) 387; (6)129 Fabrcgo, C. (5) 156 Facchin, G. (6) 38 Fadima, A.O. (7) 36 Faesslcr, R (1) 484 Failla, S.(4) 177, 187; (8) 149 Faizova, F.Kh. (4) 1,2

Fallon, L. (3) 56 Falls, F.M. (5) 165 Fambri, L. (7) 235 Fan, H.(3) 23; (4) 232 Fang, Z.G. (1) 358 Fanwick, P.E. (4) 302,323,324 Farida, T. (I) 397,399 Farooqui, F. (5) 84 Fmar, D.H. (4) 304; (7) 196 Farroha, S.M. (8) 131 Farrow, M.A. (5) 167 Fanugia, L.J. (1) 359; (6) 55 Farukshina, Z.M. (1) 563 Fathi, R (5) 107 Fa&, A. (1) 484 Fa&, J.-P. (7) 108 Faure, B.(3) 90 Fawzi, R (I) 15, 109; (8) 105 Fazio, RC. (5) 106 Fearon, K.L. (5) 98,100 Fcasson, C. (4) 100,126; (6) 72 Fedin, E.I. (4) 60 Fedorov, P.I. (4) 89 Feddoff, M. (1) 189 Feher, F.J. (1) 134 Fcistaucr, H.(4) 162 Fclding, J. ( 5 ) 101 Fellman, J.D. (7) 107 Fenesan, I. (7) 9.72 Feng, H.(4) 224 Feng, R. (4) 169 Fcnshe, D. (7) 180 Fensholdt, J. (5) 140 Fermin, M.C. (I) 1 12,246,523 Femandcq M.& F. (3) 23; (4) 232 FernandCz-Ca~taiio,C. (1) 225; (7) 15

Fmandez-Catuxo, L. (7) 113, 137, 138

Fwrer, E. (5) 156 Ferrcr, P. (6) 125 Fates, K. (4) 104; (6) 8 1 Fettingcr, J.C.(I) 232 Fey, 0. (I) 517 Fialon, M. (7) 36 Ficker, R (1) 115 Fickert, C. (8) 101 Field, L.D. (1) 64 Filipowicz, W.(5) 55 Filippov, D. (3) 86 Fillion, J. (8) 147 Filonenko, L.P. (8) 12 Film, G.F.(4) 5 1 Finet, J.-P. (I) 264

Fino,J.R (3) 78 Finocchim, P.(4) 177,187 Firouazabadi, H.(1) 424

3 66

Fischcr, A. ( I ) 295; (2) 23,24; (4) 308,309; (5) 168; (8) 38 Fischer, C. (1) 139; (3) 91 Fischer, H. (1) 253,254 Fischer, J. (1) 118,319,550; (7) 52 Fischer, P.(4) 136 Fischer, RA. (1) 366 Fischer, RW. (5) 42; (7) 21 Fischer, U. (5) 169 Fisher, M. (7) 55 Fishwick, C.W.G. (3) 50; (5) 180 Fitzgerald, J.J. (7) 224 Fitzgerald, M.C. (5) 236 Fitzpatrick, K. (3) 17 Flad, H.-J. (1) 436 Flegelova, 2.(1) 202,203 Fleischer, R (6) 48 Fleischer, U. (I) 53; (6) 9; (8) 2,3 Fleming, J.S.(1) 156 Flower, K.R. (1) 555 Fluck, E. (1) 89,324,325,529, 576; (8) 29,40 F~ces-Foce~, C. (1) 225; (7) 15 Focher, F. (5) 58 Focrstner, J. (1) 497 Fokt, 1. (5) 209 Foldespapp, Z. (5) 72 Folkerts, H. (7) 69-7 1 Foote, C.S. (5) 198 Foray, G.S. (1) 82 Foreman, M.R.St. J. (4) 321; (8) 107 Foricher, J. (1) 157 Forohar, F. (7) 104 Foucaud, A. (1) 577; (7) 168 Foucher, D.A. ( I ) 31; (7) 212 Fouqut, D. (4) 270,27 1 Fox, K.R. ( 5 ) 205 Fraanje, J. ( I ) 6 Francis, M.D. (I) 482 Frankel, D.C. (7) 196 Franz, U. (7) 265 Fraser, W. (5) 71 Frauianu, M.(8) 18 Frederick, C.A. (5) 86,228 Frederick, J.H. (1) 550 Frediani, P. (1) 86 Free, C.A. (4) 226 Freeman, S.(5) 27,34 French, S. (8) 117 Frcnkel, G.G. (7) 161 Frenkin, E.I. (7) 259,260 Frenking, G. (7) 69 Frenzel, A. (3) 27 Frenzen, G. (6) 53 Freund, A.S. (7) 103

OrganophosphorusChemishy Frick, F. (8) 3 Fridkin, M.(2) 19 Friebel, C. (7) 180 Friedman, H.S. (5) 220 Fries, K.M. (5) 7 Fritz, G. (1) 72,73 Froestl, W. (3) 4,5; (4) 218,219 Fromm, K.(1) 108 Fronczek, F.R (3) 23; (4) 232 Frost, J.W. (3) 7 Freyen, P. (1) 184,185 Fruchier, A. (6) 40 Fntchtcl, J.S. (I) 201 Frutos, D. (1) 306 Fry, A.J. (1) 409; (6) 2 Flyzuk, M.D. (1) 240 Fu, D.J. (5) 246,264 Fu, L. (8) 51. Fu, P.P. (8) 152 Fuchs, E. ( I ) 484 Fuchs, P.L. (6) 133 Fuelscher, M.P. (1) 565 Fuhler, R (7) 91 Fuji, K. (4)-274; (5) 194; (6) 76, 77.90

Fujihar, H. (1) 68; (8) 49 Fujii, N. (4) 35 Fujimoto, M.(4) 168 Fujimoto, T. (8) 39 Fujita, J. (1) 84 Fujita, T. (6) 106 Fujiwara, H. (6) 128 Fujiwara, M.( I ) 354 Fukui, Y. (4) 24 Fukushima, K. (4) 75 Furuichi, T. (1) 5 1 Furukawa, N. (1) 68; (8) 49 Furusawa, K. (3) 59; (5) 148 Fyfe, C.A. (1) 23 1 Gabbai, F.P. (1) 474; (3) 99; (7) 82

Gabold, P.(7) 26, 192; (8) 8 Gabor, B. (1) 502 Gabriel, K.M. (7) 99 Gacsbaitz, E. (5) 109 Gaffney, B.L. (5) 224 Gainullin, R.M. (8) 4 1 Gajda, T. (1) 2 16; (4) 174 Gal, J.-F. (7) 7 Galakhov, M. (1) 1 1 1 Galiaskarova, F.M. (3) 37,49 Gallagher, M.J. (1) 205; (3) 24; (4) 24 1 Galliot, C. (1) 297; (7) 120 Gallo, M.A. (1) 183

Galushko, S.V.(4) 233 Gambarolla, S. (6) 47 Gambino, J. (5) 58 Gamliel, A. (4) 240 Gancarz, I. (4) 185 Gancarz, R (4) 179,184,185 Gandolfo, F. (1) 545 Gani, D. (4) 30,65,66 Ganis, P. (6) 38 Ganter, C. (1) 27 Gao, Q.Y. (5) 272 Gao, RY. (8) 148 Gao, X. (1) 240; (7) 173,174 Garbay-Jaureguibeny,C. (4) 2 11 Garbe, R (7) 178 Garcia, J. (4) 118 Garcia, RG. (5) 156 Garcia Alonso, F.J. (7) 113, 137, 138

Garcia-Echevema, C. (3) 62; (5) 65

Garcia-Granda,S.(6) 6; (7) 137, 171,172,183

Garcia-Montalvo, V. (1) 378; (7) 206

Garcia-Repetto,R (8) 129 Garcia y Garcia, P. (1) 378; (7) 206

Gardiner, J.M. (5) 27, 173 Garduno, C. (3) 5 I Garestier, T. (5) 206,207 Garifzyanova, G.G. (4) 45,47,48; (8) 82

Garin, J. (6) 130 Garrido, 1. (8) 129 Garrigucs, B.(4) 178 Garrigucs, E.(1) 288 Garrigues, P.(8) 139,142 Garrity, M. (7) 107 Gaspar, P.P. (1) 564 Gasparrini, F. (1) 347 Gau, A.I. (7) 79 Gaumont, A.-C. (I) 130 Gaulheron, B. (1) 159 Gavrilov, K.M. (2) 3 Gavrilov, V.V. (1) 169 Gdaniec, Z. (5) 168 Geib, S.J. (7) 119 Geisel, U. (4) 3 1 Geissler, B. (1) 49 1 Gelbard, G. (1) 322 Gcllon, G. (6) 138 Gengembre, L. (7) 234 Genov, D.G. (4) 297; (8) 13,14, 33

Genschik, P. (5) 55 Gentil, E. (5) 25 1

Author Inder Gentsch, C.(3)4,5;(4)218,219 G e d h y , M. (I) 439 George, C. (7)104 Gerfm, T. (1) 116 Gerhardt, K.O.(8)145 Gerinun, S.(5) 83

Gerratt, J. (I) 258 Geue,RJ. (5) 216 Geycr. C.R (5) 227 Ghanbaja, J. (7)226 Gharbaoui, T.(3)9;(4)193 Gharbi, A. (8)98 Ghassemzadek, M.(1) 401;(8)99 Gkardi. E. (5) 56 Gholivand, K.(4)59 Ghribi, A. (4) 159 Gibson, S.E. (6)50 Gibson, V.C. (1) 437;(3) 103 Gierling, K.(1) I09 Gijsen, H.J.M. (6) 137 Gilard, V. (8)38 G i l d , R (7) 104 Gilbertson, S.R (I) 49, 143,144 Gilheany, D.G. (8)71 Gilyarov, V.A. (7)8 Gimeno, M.C. (I) 364;(6)70 Giorgi, G. (1) 267 Guard, J.P. (6) 1 17 Girardet, J.-L.(3)60;(5) 3 Girol, C. (4)268 Giver, E.(5) 257 Giver, L.(5) 177 Gladiali, S.(1) 543 Glaser, G.(1) 501 Glasgow, K.C.(5) 213 Gleitet, R (1) 506 Gleria, M. (7)235 Gloede, J. (4)17 Glonek, T.(8) 17 Glowaclo, 2.(4)295 Glueck, D.S. (1) 457,458 Gluth, M.(3)27 Gmeiner, W.H.(5) 221 Goasdoue,N.(7)197 Goda, K.(I) 218;(6)28 Godfrey, S.M. (1) 180;(3) 21 Gcdovikov, N.N.(8) 119 Godry, B.(1) 323 G6be1, M.W. (3) 76;(5) 172 Goehler, D. (7)102 Goenechea, S.(8) 128 Goerlich, J.R. (1) 241,278,312, 445 Goesmann, H.(7)74,75 Goette, B.(1) 259 Golen, J.A. (4)299 Gololobov, Yu.G. (1) 170,419

367 GO~OVM, E.B.(1) 248,249 Golovatyi, 0.R (3)22;(4)233 Golubin, A.I. (4)249 Gomeq J.A. (1) 183 Gomez-Elipe, P.(7)4,113, 137, 138;(8)67 Gonnet, F. (5) 262 Gontarev, S.V. (3) 75,79;(5) 201 Gonygou, M.(8) 104 Gonzaleq C. (5) 83,197 Gonzalez, P.A. (7) I 13 Gordano, A. (5) 233 Gordillo, B.(3) 5 1 Gornikka, H.(1) 522 Gordrhov, V.G. (1) 120 Gossage, RA. (1) 1 17 Gosselin, G. (3) 60;(5) 3,60 Goubitz., K. (1) 6 Gough, G.R (5)88 Gounev, T.K. ( I ) 301 Gouyette, A. (5) 255 Gouygou, M. (1) 433 Gozin, M. (1) 60 Grachev, M.K. (3)41,48 Graczyk, P.P. (I) 355,382-384; (8)92 Greffeul, M. (7) 108 Graham, E.E. (7)144 Graiff, C. (1) 373,374 Grajkowski, A. (5) 92 Gramlich, V. (1) 29, 116,164 Granata, A. (8)79 Grandas, A. (3) 69 Grasso, P.(8) 154 Gravestock, M.B. (1) 215 Grebe, J. (7)73 Green, D. (4)125 Grecn, J.B. (7)217 Green, M.(1) 505 Green, S.St. C. (8)48 Greenberg, M.M. (5) 78,185 Greene, T.M. (I) 260 Greer, RW.(7)236 Gref, A. (1) 16,26 Grckov, L.I. (I) 121 Grenda, V.J. (4)151 Grew, J.-M. (4)81 Grewal, R.S. (3) 77 Grice, I.D. (1) 205;(3) 24 Griffiths, D.V. (4)266,267;(6)4; (8)34-36 Grimths, P.A. (4)266,267;(6)4; (8)34,35 Grigor'ev, E.V. (2)12, 13,15;(4) 165,216,217 Grimaud, J. (4)136 Grimmer, A.R (8)3

Grishkun, E.V. (1) 296;(4)93,94,

233 Grison, C.(4)159;(6)100,107

Grissom. 1.W. (1) 299 Grobe, J. (1) 494,498,500 Groegcr, H.(4)180;(8)32 Gronchi, G.(1) 264 Grondey, H. (1) 23 1 Gronowitz, S.(5) 61 Gronwald, A. (7) 198 Grossmann. G. (1) 198;(4)293, 3 16,320 Grote, C.W.(2)8 Grotjahn, D.B. (I) 3 Griin, K.(I) 107,517,519 Griin, M.(7)74 Griitnnacher, H.(I) 53; (6)9 Grundei, S.(1) 89 Grum, G.L. (7)236 Gruncich, J.A. (7)216 GIUSS,U. (8)48 Gruttner, C.(1) 321 GTyBpIov, S.M. (5) 110, I 1 1, I23 GrynszpM, F. (4) 18 Gu, H.(8)137,138 Gu,Q.M. (5) 44 Guadanrama, G. (3) 5 1 Gudat, D. (1) 77,510,520;(6)48; (8) 11 GuUet, P. (4)28,29 Guelpen, J.H. (7)189 Guerret, 0.(1) 272;(6)7 Guga, P.(5) 92.93 Guhrs, K.H. (5)72 Guillancux, D.(1) 16 Guillawne, M. (6)26 Guillernette, G. (4)28 Guillemin, J.-C. (8)81 Guillot, D.E. (7)292 GUI~~-PI,UCUCSCU, M. (4)277;(6) 93,94 Gulenko, A.N. (I) 456 Gulyaeva, ul.R (7)6;(8) 92,115 Gulyukina, N.S.(I) 249 Guo, L.(2)9 Gupta, A.D. (7)115 Gupta, K.C.(3)73;(5) 203 Gupta, RC. (8) 159 Gurevich, I.E. (4)90 Gusarova, N.K. (1) 87,119,120, 350 Gusev, D.V. (3) 35;(4)235;(8) 108 Guzaev, A. (3) 61,74;(5) 64

Habboush, A.E. (8)13 1

OrganophoqhorusChemistry

3 68 Habel, L.W.(5) 32,33 Habus, 1. (5) 74,76,108 Haebali, P. (5) 137 Haegele, G.(4) 207; (7) 91; (8) 48 Haelm, J.-P. (4) 158 Haemers, A. (4) 191,201 Hiher, R (3) 62; (5) 65,91 Hiker, M. (7) 11 H a , L.A. (5) 238,243,245,248, 249,268

Hafner, K.(1) 440 Hager, H. (7)124 Hager, R (7) 56,59,63 Hagmm, W.K. (4) 99 Hahmr, S.(5) 247 Haiduc, I. (7)68, 199,201,202, 294; (8) 93

Hakimelahi, G.H.(5) 37,50 Hale, RL. (4) 212 Hall, C.D. (1) 222; (6) 33 Hall, J. (5) 55 Hall, RG. (3) 4,5; (4) 218,219 Hamada, Y.(3) 15; (6) 105 Hamamichi, N. (6) 106 Hamashima, H. (1) 127 Hamelin, J. (1) 562 Hamilton, R (3) 6; (6) 103 Hamilton, T.P. (I) 53 1 Hammen, RF. (7)284 Hammer, RP.(3) 20,23; (4) 232; (5) 96 Hammerschrm'dt, F. (4) 50, 139, 140 Hammond, G.B.(4) 299 Hampel, A. (5) 87 Hampel, F. (1) 422; (2) 7; (6) 1 1; (8) 8 Han, M.J. (7) 126,127 Handma, T.(6) 19 Hanaoka, K. (5) 8 Hancox, E.L.(5) 23 1 Handel, H. (4) 77 Hanna, N.B.(5) 84 Hanningcr, A. (4) 50 Hansen, K.B. (2) 8; (4) 280 Hmscn, L. (1) 365 Hanson, B.E.(1) 42, 129 Hantz, A. (7) 72 Hanumantharayudu, T.A. (4) 38 Huger, M.J.P. (1) 534; (4) 288-290; (6) 13 Harkema, S.(4) 15 Harms, K.(1) 401; (7) 73,74 Hanis, C.M. (5) 18 1 Hanis, K. (7) 178; (8) 99 Harris, R.K. (8) 50 Harris,T.M. (5) 181

Harrison, K.A. (5) 53 Hanison, RK. (4) 99 H m a n n , M. (1) 75 Harvey, P.J. (1) 205; (3) 24 Hashimoto, H.(3) 72 Hashimoto, Y.(4) 24; (5) 119 Hashime, T. (5) 222,260 Hasselbring, R (1) 118; (7) 185 Hatam, M. (4) 190 Hatanaka, M.(6) 27 Haugan, J.A. (6) 109 Haupt, E.T.K. (1) 367 Hausel, R (1) 164; (2) 8 Hausen, H.D. (1) 88,89,94 Hauser, K. (3) 5; (4) 218 Haw, J.F. (7)221 Hawkins, M.E.(5) 165 Hay, A. (5) 34 Hayakawa, M.(3) 93 Hayakawa, T. (7) 27 1,277-279 Hayasc, S.(1) 233,354 Hayashi, C. (1) 25 Hayashi, S.(1) 233; (6) 79 Hayashi, T.(1) 24,25,123 Hayashi, Y.(1) 12 Hayes, R.F. (7) 103 He, S.J. (4) 82 He, Z.-J. (4) 82.83.227 Heath, G.A. (7) 191 Hcaton, P.A. (5) 47 Heckcl, M. (1) 115,294; (6) 8 Heckmann, G. (1) 76,88,89,324, 325,436,529,576; (8) 29,40

Hegemann, M. (1) 494,498,500 Hcijtink, R (5) 5 Hcim, U. (1) 53; (6) 9 Heinickc, J. (3) 109 Hcisler, A. (4) 207 Helene, C. (5) 206,207 Hellcr, A. (5) 199 Heller, D. (1) 45,139; (3) 91 Helmchen, G.(1) 50,63 Henderson, W. (1) 395; (3) 8; (4) 3 13

Hendrickson, J.B. (1) 340; (7) 24 Hcriliski, J. (4) 54 Hennig, R (1) 441,442 Henry, J.R (6) 120 Herault, D.A. (4) 3 1 Herberich, G.E.(1) 158 H e r b s t k , R. (3) 27 Herdewijn, P.(5) 142,158 Hcnm, H. (6) 46 Herkw, M. (7) 69 Hermann, P. (4) 84 Hernan&z, J. (3) 5 1 Hcmandez-Ortega, S.(7) 294

Herold, S.(1) 1 16 Herpin, T.F. (4) 124 Hcmno-Sacnz, D. (8) 152 Hcrrlcin, M.K. (3) 80; (5) 171,204 Hcmnann, E. (7) 198 Herrmann, P. (1) 533 H m a n n , W.A. (I) 7,253,254 Hermg, K.J. (4) 28 1 Hettich, RL. (5) 215,259 Heydt, H. (1) 446,484 Hey-Hawkins, E.(1) 108,110 Hibbs, D.E. (1) 482 Higano, M. (7) 291 Higashimdo, K. (7) 277,278 H i p n , A.P. (5) 36 Hill, A.F. (1) 460 Hill, F. (5) 157 Hill, J.M. (4) 4 1 Hill, T.S. (3) 19; (5) 95 Hillcnkamp, F. (5) 247 Hillcr, W. (1) I 15; (7) 69 Hilts, RW. (7) 173 Himdi-Kabbab, S.(1) 562 Hindahl, K.(1) 107,5 16 Hindle, R (8) 147 Hingexty, B.E.(5) 223 Hirakawa, E. (1) 192 Hirao, T. ( I ) 18 Hironaka, K.(7) 271,277-279 Hirose. K. (1) 191 Hirose, R (6) 106 Hirschmann, R. (4) 256 Hirth, W.-A. (I) 517.519 Hitchcock, P.B.(1) 38,65,503, 504,552,555,558

Ho,J.(I) 112 Ho, N.-H. (3) 67; (5) 67,74,75 Hobza, P. (8) 7 Hockless, D.C.R (1) 67 Hodge, P. (6) 115 HGnle, W. (1) 436 Hoatbauer, W. (8) 3 Hoffmann, A. (1) 480 Hoffmann, M. (4) 295 Hofllmann, R (3) 87; (6) 53 Hoffmum, T. (3) 87 Hohann, M. (1) 260 Hofstadlcr, S.A. (5) 273 Hog& J.K. (I) 154 Holand, S.(1) 545 Holderbcrg,A.W. (1) 510 Holgq, R (7) 58 Holland, P.M. (1) 348 Holleboek, J. (1) 566 Hollcy, W.K. (7) 3 Holmes, J.M. (8) 53 Holmes, RR. (2) 2,16; (8) 53

Author Index Holy, A. ( 5 ) 28-30 Holz,J.(l) 11,45,59, 139;(3)91 (6) 43 HOI, Y.-S. Honeyman, C.H. (1) 31; (7) 215 Hong, J.E. (4) 110, 166,269; (6) 97 Hmg, M.-C. (1) 47 Hong, S.Y. (7) 220 Hopkins, P.B. (5) 214 Hoppc, S.(1) 162 Hw, T.S.A. (1) 358 Horndler, C. (5) 136 Hmfeldt, A.B. ( 5 ) 61 Humyak, I. (8) 102 Horsburgh, C.E.R (6) 46 Horst, RL. (6) 135 Horstmann, S.(7) 10, 11 HOSM@, B.D. (6) 139 Hossain, M.M. (1) 504 Houalla, D. (2) 20 Houlton, J.S. (4) 124 Houser, J.J. (1) 491 Houston, C.T. ( 5 ) 257 Howard, J.A.K. (1) 387; (4) 155; (6) 129 Howard, S.T. (1) 256 Howie, RA.(1) 48 Hoye, T.R (4) 172 Hoyl, T.R (6) 96 Hu, B.F. (4) 63 Huang, C.Y. ( 5 ) 160 Huang, D. (1) 299 Huang,F.Q. ( 5 ) 59 Huang, Q. ( 5 ) 107; (8) 65 Huang, T.B. (3) 43 HUM&W.(4) 115,215; (6) 99 HUM&W.F. (1) 388 HUM&X.(1) 316; (4) 107 Huang, Y.(1) 231; (2) 26; (3) 45; (8) 75-78,114 Huch, V.(1) 433,513; (3) 106 Hudson,H.R (1) 429; (8) 48 Huebier, K.(1) 7 I Hughes, D.L. (1) 200 Hulst, R (3) 17 Humrt, C. (4) 178 Hunickesmith, S.P.( 5 ) 8 1 Hunter, W.N. (5) 23 1 Hunnan, B.T. (1) 534; (4) 288; (6) 13 Hurst, G.B. (5) 258,259,266 Hutsthouse, M.B. (1) 156,482; (7) 117,207 Huscbye, S.(8) 69 Husman, W. (4) 125 Hussain, M.S.(4) 300 HH.-P. (3) 9; (4) 193

369 Hutchison,J.C. (7) 241,242 Huttncr, G.(I) 57-59; (3) 92 Hutton, G.(6) 58 Huy, N.H.T. (1) 463,524 Hwang, J.J. (7) 23 1 Hwu, J.R (5) 37,50 Iacuone, A. (6) 80 Iannitti, P. ( 5 ) 269 Ibim, S.E.(7) 249 Ibrahim, Y.A. ( 1) 4 15 Ichihashi, A. (8) 141 rchikawa, J. (4) 173 lchimura, S. (7) 156 I&, H. ( 5 ) 219 Iden, C.R (5) 237,256 Iftime, G.(1) 30 Igau, A. (1) 138,245,528 Iglesias, B. (6) 110 Ignat’ev, V.M.(4) 96,97 lim~ra,S.(3) 59; ( 5 ) 148 Iino, Y.(7) 46 Ikari, K. (1) 418 Dreda, H. (5) 194 Ma,I. (1) 18 11ikG.(4) 119 ll’yasov. R.N. (1) 236 imPmOr0,T. (1) 188, 190-192 [mamura, M.(3) 72 Imanishi, T. (1)416; (5) 125,126 hbsch, J.-L. (3) 60; (5) 3,60, 130,131 Imhoff, P.(7)189 Immel, F. (1) 498, SO0 Imrie, C. (1) 429 Indhikyan, M.G. (7) 110 Inguimbert, N.(4) 23 1; (7) 37 Inoue, K.(7)125,140 Inoue, S.(3) 108; (4) 40 lnouc, T. (1) 192 Inubushi, A. (7)275,277-279 Ioannou, P.V.(4) 148 Ionin, B.I. (1) 285,286; (4) 90.96, 97 Ionkin, A.S. (1) 475; (3) 100 Iriye, R (8) 39 Ironside, M.D.(1) 342; (6) 64 I S ~ C V G.M. ~, (1) 236 Ishakova, G.G. (1) 169 Ishida, A. (6) 27 Ishihanda, M. (7)290 Ishikaws,M.(7)164 lshmaevq E.A. (7)6; (8) 92,115 Ismail, M.M. (1) 228; (7)43 Isuno, T. ( 5 ) 145 Itagaki, M.(2) 30

ltaya, T. (7) 140 lto, J. (7) 289 lto, N. (5) 229 110.0. (7) 150 It6, S. (1) 213,214,218,291,444; (6) 28-30; (7) 149 Ito, T. (7)155 Ito, Y. (1) 127 Ivanov, A.A. (8) 157 Ivanov, B.E.(4) 53 lvanova, G.G.(8) 157 Ivonin, S.P. (1) 282,283 Iwabuchi, H.(4) 209 Iwamoto, M.(1) 365 lwanagq H.(4) 285 lwasalo, S.(4) 24; (6) 114 lwasaki, T. (1) 354 IYW, RP. (3) 67; ( 5 ) 67,69,74-76, 108,135 Izquierdo-Martin, M.(4) 99 Jackson, D.A. (1) 3 18; (6) 69 Jacob, A. (5) 267 Jagex, L.(4) 23 1; (7) 37 Jacket, J. (3)4,5; (4) 218,219 Jaglowski, A.J. (7) 99 Jain, M.L. (5) 50 Jain, S.C. ( 5 ) 232 Jakle, F. (1) 52 Jakobi, RA. (1) 32 1 James, M.A. (1) 402 Jamison, G.M. (1) 507 Janata, J. (8) 118 Jancke, H. (4) 325; (8) 86 Jancke, K. (4) 325; (8) 86 Janda. K.D. (4) 68; ( 5 ) 12 Jang, T.Y. (7)126 Jan& W.B. (4) 269 Jankowski, S.(1) 533; (4) 84; (8) 125 Janoschck, R (1) 39,100 Janousek, 2.(6) 26 Jansen, M.(1) 400, (3) 18; (8) 3 Janscn, RG. (4) 15 Jruwns, J. (5) 58 Jpnsstn, RA.J. (1) 361; (8) 89,W Jareserijman, E.A. (5) 225 Jaszay, Z.M. (8) 116 Jayaraman, K. (3) 19; (5) 95 Jayarsman,M. (7)40 JeffG.R (6) 50 Jei, T. (4) 208 Jekel. A.P. (7)124 Jadiins, D.J. (4) 27 Jenkins, I.D. (1) 205; (3) 24; (4) 24 1

3 70

Jenkins, S.A. (7) 252-254 Jenkins, T.C. (5) 205 Jensen, G.A. (7)285 Jtrbme, R (6) 13 1 Jeschke, G. (4) 293 Jeske, J. (1) 237,287,493,540 Ji, H.J. (7) 126, 127 Jiang, H. (8) 58 Jiang, J. (I) 304 Jiang, Q. (1) 61 Jiang, X.-C. (4) 169 Jiang, 2.-H. (8) 79 Jiang, Z.W. (5) 69 Jim, X.-Y. (4) 191 Jin, X.L. (4) 307 Jin, Y. (3) 54; (4) 34 Jin, Y.C.(4) 227 ling, P.C. (5) 44 Jobson, RB. (4) I5 1 Jochcm, G. (I) 292,423,449,476, 477; (3) 101; (6) 10, 12, 15, 16; (8) 26,73, 110 Joerg, S.(I) 257 Johansson, N.G.(5) 61 John, G.R (1) 174 Johns, R.B. (4) 61 Johnson, J.A. (1) 558 Johnson, N. (6) 135 Johnson, S.E.(5) 108; (8) 106 Johnston, C.R (6) 104 Johnston, D.H. (5) 213 Johnstone, C. (1) 186 Joliez, S. (6) 100 Jolliff, T.(6) 58 Jones, C.(1) 460,482,503,505 Jones, P.G. (1) 237,287,295,364, 493,540; (2) 23,24; (4) 308, 309; (6) 70; (8) 32,38,57 Jones, R.A. ( I ) 93; (5) 70,224 Jones, T.R.B. (1) 268 Jonini, A. (8) 98 Jorgensen, P.N. (5) 143 Josowicz, M. (8) 118 Joswig, C. (5) 7 Jouaiti, A. (1) 439 Joubran, C. (1) 3 Jouin, P. (4) 25 1 Jovin, T.M. (5) 225 Ju, J.-Y. (4) 167 Jubault, P. (4) 100,126; (6) 72 Juhasz, P. (5) 238,248,249 Julino, M. (1) 486-488 Julius, M.(6) 53 Ju, C.-H. (I) 243 Jw, C.-L. (7) 121 J u , M.-J. (7) 2 14 Jung, G. (1) 20 I

Organophosphorus Chemistry Jung, K.E. (5) 272 J u g , K.-Y. (2) 8 J u g , 0.4. (7) 213,214,248 Jurado,J.R (7) 268,269 Jurinkc, C. (5) 267 Jurkschat, K. (1) 162 Jursic, B.S. (1) 483 Just, G. (3) 53-55; (5) 122 Juta, S.(7) 112 Juwik, P. (1) 185 Kabachnik, M.I. (1) 3 14,338,353; (4) 49; (7) 8, 19

Kabachnik, M.M. (1) 167; (4) 260 Kabelae, M. (8) 7 Knbuyama, Y. (4) 24 Kadokura, M. (5) 169 Kadyko, M.I.(4) 60 Kadyrov, A.A. (4) 308 Kadyrov,R.( I ) 11,139; (3) 91, 109

Kaehlig, H.(4) 139 Kafarski, P. (4) 136, 197,223, 252,296

Kagan, H.B. (1) 11, 16,26,303 Kagechika, H. (5) 119 Kaim, W.(1) 436 Kaiser, V. (4) 3 16; (8) 2 Kajiwara, M.(7) 95-97,282,283 Knjiwara, N. (7) 84 Kakehi, A. (6) 122, 123; (7) 41 Kakkar, A.K. (I) 148 Kakkar, V.V. (4) 125 Kalbibr, H.R. (3) 87 Kalchenko, V.I. (4) 14, 16, 19,20; (8) 112

Kalinichenko, E.N.(5) 170 Kalinkinn, A.L. (3) 19; (5) 95 Kalyanova, RM. (1) 338 Kamalov, R.M. (7) 27 Kamberger, W. (6) 44 Kamel, N. (I) 484 Kamer, P.C.J. (1) 6.62; (3) 3 1 Kamcshima, T. (7) 84,275,276 Kamikawa, T. (1) 123 Kaminski, 0. (1) 464 Kanayama, A. (4) 75 Kaneko, M.(4) 35 Kane-Maguire, L.A.P. (1) 174 Kaneta,N. (1) 12 Kmg, B.4. (1) 47 K m g D.-H. (4) 188 Kan& H.-C. (7) 70, 179 Kang, J. (1) 124 Kang, J.H. (7) 288 KMg, Y.B. (1) 67.90

Kanlin, G.P.(1) 229; (7) 18 Kantoci, D. (4) 198 Kanzlen, S.(4) 194 Kao, J.L.F. (5) 195,218 Kar, K.K. (7) 141 Karadakov, P.B. (1) 258 Karaghiosoff, K. (1) 476; (3) 101; (6) 15

Karandi, I. (8) 119 Karas, M. (5) 247 Karaski, A.A. (1) 242 Karataeva, F.Kh. (4) 282 Karger, B.L. (5) 271 Kargin, Yu.M. (4) 4 Karieva, G.A. (8) 95 Karim, K. (4) 266,267; (6) 4; (8) 34-36

Karimov, K.S. (8) 95 Karlsson, G. (3) 5; (4) 2 18 Karlstedt, N.B. (I) 178 Karodia, N. (6) 46 Karpeisky, A. (5) 137 Karr, K.K. (7) 145, 147 Karsch, H.H. ( I ) I 14, 1 15,294; (6) 8,49

Kanvowski, B. (5) 92,93 Kasaka, T.(8) 39 Kashemirov, B.A. (4) 167,168 Kash~n,A.N. (8) 157 Kashiwabara, K. (I) 84 Kataeva, O.N. (4) 3 1 1 Katooka, Y. (1) 44 Kato, K.(2) 2 1 Kato, M.(7) 95 Kalri%, A.R (I) 304 Kattesch, K.V. (7) 187 Katti, K.V. (3) 28,29; (7) 66 Kau, J.Y. (7) 23 I K a u f m m , B. ( I ) 239 Knufmann, R (5) 239 Koukovat, T. (I) 35 1; (4) 308; (8) 32

Kawaguchi, T.(1) 354 Kawakami, T. (1) 369 Knwashima, T. (2) 21; (4) 285; (6) 2483

Kozankova, M.A. (1) 290,472, 473; (3) 102; (7) 30-34

Keanrey, M.E.(7) 103 Keck, H. (I) 271; (8) 146 Kce, T.P. (3) 89; (4) 130,13 I Keglevich, G.(1) 128,308,532, 575; (4) 239,287; (8) 60

Kehler, J. (5) 101 Kcinan, E. (6) 134 Keitel, I. (4) 17 Kcller, U.(6) 49

Author Index Kellogg, RM. (3) 17 Kelly, N.M. (6) 102 Kernpe, D. (1) 59 Kempe, R (1) 25 1 Kende, A.S. (6) 120 Kennepohl, D.K. (2) 4 Kenttamaa, H.I. (1) 271,427; (8) 146 Kerbal, A. (1) 220 KCK, W.J. (1) 186 Kerres, J. (7) 286 Kers, A. (5) 17; (8) 80 Kers, I. (5) 17; (8) 80 Kerwin, J.F. (4) 192 Kesicki, E.A. (5) 182 Kessler, J.M. (1) 55 1; (8) 84 Keyte, RW. (7) 203,205 Khailova, N.A. (7) 27 Khalaf, H.I. (8) 131 Khalmukhamedova, M.V. (4) 149; (8) 95 Khan,N. (5) 58 Khanipova, M.G. (2) 11 Khare, A.B. (4) 147 Khtl'ko, M.Ya. (1) 120 Khodak, A.A. (7) 19 Khosravi, M. (4) 59 Khusainova, N.G. (1) 563; (8) 28 Kieczykowski, G.R (4) 151 Kiefer, M. (1) 63 Kiefer, W. (8) 101 Kim, A.-K. (7) 244 Kim, D.Y. (4) 156, 157 Kim, H.-K. (7) 245 Kim, J.C.(7) 80 Kim, J.-H. (4) 275; (6) 89 Kim, J.I. (1) 124 Kim, J . 4 . (4) 70 Kun, K. (6) 34 Kim, K.S. (7) 244,245 Kim, S.-G. (3) 57; ( 5 ) 68 Kim, T.H. (4) 157; (6) 1 I 1 Kim, Y.B. (7) 220,227 Kimura, E.(7) 85 Kimura, K. (4) 24 Kimura, T. (7) 283 Kinas, R (4) 60 Kingenberg, E.H. (7) 229 Kinoshita, T.(5) 244 Kirchmeier, RL. (7) 119 Kueev, V. (7) 258 Kirn, A. (3) 60; (5) 3 Kirpekar, F.(5) 141,247 Kiselev, V.D. (1) 169 Kiseleva, O.A. (7) 163 Kishikawa, K.(1) 188 Kisielowski, L. (1) 422; (2) 7; (6)

371 11 Kitajima, R. (7) 150 Kitamura, K. (1) 44 Kitamura, M. (4) 205 Kitao, Y. (6) 106 Kiuchi, M. (6) 106 Kivekas, R (1) 238 Klar, U.(6) 25 Klaui, W. (7) 91 Klcbs, K. (3) 5; (4) 218 Klem,R.E.(5) 189 Kless,A. (1) 11,45,59,139; (3) 91 Klimovitskii,E.N. (4) 165 Klingcbiel, U. (3) 27 Klintschar, G. (I) 150 Klostcnnann, K. (4) 3 16 Kneissle, W. (1) 109 Knight, D.A. (1) 232 Knight, D.W. (1) 215 Knobler, C.B. (8) 106 Knoch, F.A. (1) 279,499; (7) 192; (8) 8 Knochel, P. (1) 280; (3) 25 Knochenmuss, R (5) 253 Knolle, J. (5) 117 Knop, 0. (1) 402 Kniihl, G. (1) 50 Kobayashi, H. (1) 2; (8) 39 Kobayashi, J. (1) 3 10 Kobayashi, T. (6) 135 Kobylanska, A. (4) 3 17; (5) 92 Koch, F.A. (7) 26 Koch, R (4) 327; (6) 74; (8) 6 Kochcr, F. (5) 262 Koda, G. (6) 32 Koehler, K.F. (4) 328 Koeller, K.J. (4) 181 Koenig, M. (1) 36,433 Koh, Y.J.(4) 103 Kohlhaas, K.L.(4) 192 Kohlpainher, C.W. ( I ) 7 Koide, T. (1) 396 Koishihara, Y. (5) 126 Koiso, Y. (6) 114 Kojima, M. (7) 264,265 Kokin, K. (6) 79 Kollc, U. (1) 462 Kolodyazhnyi, 0.1. (I) 296; (3) 22; (4) 93,94,233 Kolomietz, A.F. (4) 322 Kolomnikova, G.D. (1) 419 Komaki, A. (7) 277-279 Komarov, I.V. (1) 247 Komen, C.M.D. (1) 28 1 Kondoh, K. (1) 4 16 Kong, M.S. (4) 156,157

Konovalov, A.I. (1) 169,508 Konovalova, I.V. (2) 11; (4) 236 Kooijman, H. (3) 3 1; (7) 76,188 Kool, E.T.(5) 80,89, 179, 196 Koprowski, M. (1) 347; (4) 72,73 Korber, N. (1) 408 Korkin, A.A. (8) 5 Kormachev, V.V. (4) 88,89 Kornilov, M.Yu. (1) 247 Korotecv. A.M. (8) 45 Koroteev. M.P. (8) 45 Korshun, V.A. (3) 75,79; (5) 201 Kosaka, T. (5) 244 Kosower, E.M. (1) 224; (7) 14 Koster, H. ( 5 ) 73,246,264,267 Kostina, T.K. (4) 264 Kostitsyn, A.B. (1) 166,446 Kostyanovsky, RG. (4) 328 Kostyumina, T.G. (8) 10 Koszuk, J.F. (4) 101 Kotila, S. (1) 5 10; (6) 47,48 Kotter, S. (5) 264 Kottman, H. (1) 7 Koutsantonis, G.A. (1) 95 Kovacs, I. (1) 72,73 Kovalev, V.V. (4) 91 Kowalak, J.A. (5) 260 Kowaluk, E.A. (4) 192 Kozawa, K. ( 1) 26 1 Koziol, A.E. (7) 3 Koziolkiewicz, M. (5) 92 Kozlov, E.S.(1) 284 Kozlova, G.V. (1) 350 Koma, L. (8) 102 K r ; ~ t zH.-B. , (1) 60 Kraemer, R (7) 120 Krafl, D. (1) 321 Kraft, H.(1) 465 Kramer, B. (1) 535; (4) 312; (6) 14 Kranenburg, M. (1) 6 Krannich, L.K. (1) 92 Krant, M.(4) 259; (6) 73; (8) 9, 70,72 Kraszwski, A. (5) 17,41; (8) 80 Kratky, C. (1) 22,23,43 Kraust, H.W. (3) 97; (4) 199 Krause, W.E. (8) 113 Knutscheid, H. (1) 406 Krawczyk, E.(4) 72,73 Krawczyk, H. (4) 195 Krchnak, V. (1) 202,203 Krebs, B. (1) 494,498,500 Kreitmeir, P. (1) 149 Kremer, T.(8) 8 Krcpinsky, J.I. (5) 187 Kresinski, RA. (8) 14 Krctschmann, M. (7) 136

OrganophosphorusChemistry

3 72 Kreuzfeld, H.J. (3) 97 Krickemeyer, E. (1) 405 Krishnaiah, M. (4) 7,10,3 19 Krishnamurthy, S.S.(8)47 Krishnamurthy, V.V. (8) 59 Kroening, H. (7) 157, 160 Krotz, A.H. ( 5 ) 97,l IS, 116 Krueger, K. (1) 198; (4) 293,3 16, 320; (7) 94 Kruger, C.(1) 50 1,502 Kruhs, W. (1) 513; (3) 106 W i g , J. (5) 5 Krylova, T.O.(1) 170,419 Krym;mskn-Olejnik, E. (3) 63; ( 5 ) 184 Kubicki, M.M. (1) 159 Kubisa, P. (1) 426 Kubiyama, K. (8) 158 Kuchel, P.W.(8) 19 Kuchcn, W. (1) 27 1;(4) 292; (8) 146 Kuchmanchi, S.( 5 ) 181 Kudclska, W. (4) 44 Kuehlung, S. (7) 5 1 Kiihnle, F.N.M. (3) 93 Kuge,S. (1)418 Kuharc~k,S.E. (7) 87,88,92,223, 224,232 Kuhn, H. ( 5 ) 150 Kuhn,N. (8) 105 Kuimelis, RG. ( 5 ) 103-105 Kukhar', V.P. (2) 12 Kukhareva, T.S.(4) 322 Kuklev, D. (6) 117 Kulak, T.I. ( 5 ) 147 Kulichikhin, V.G. (7) 257,259, 260 Kulzer, F.(1) 477; (6) 16 Kumar, D. (7) 1 15 Kumar, N.J. (4) 10 Kumar, P. (3) 73; ( 5 ) 203 Kumazawa, T. (8) 126 Kummer, S.(1) 279 Kuncrth, D.C. (7) 284 Kung, P.P. ( 5 ) 224 Kunkel, F. (7) 70 Kuntz,RR(7)66 Kuo, D.W.(4) 99 Kupka, T. (7) 116,118 Kuptosov, S.(7) 262 Kurita, J. (1) 346 Kuromaru, K. ( 5 ) 125 Kurov, G.N.(7) 122 Kurtzweil, M.L. (1) 193 Kuryama, T.(7) 151 Kurz, M. (3) 76; ( 5 ) 172 Kustrya, D.N. (2) 15

Kusumoto, S. (3) 66; (4) 33,79 Kusuoku, H. (3) 59; (5) 148 Kutscher, B.(2) 24; (8) 38 Kutschera, D. (1) 23 Kutzclnigg, W. (8)3 Kuwano, R (1) 127 Kuyl-Yeheskiely, E.(3) 86 Kuz'min, E.A. (2) 6 Kurmina, L.G. (1) 104 Kuznetsova, E.E.(I) 350 Kvasyuk, E.I. ( 5 ) 147 Kwon, S.-K. (7) 121 Kwon, Y. (4) 1 10 Kyoda, M. (8) 39 Laali, K.K. (1) 491 Labme, J.-F. (7) 106,108 Labarre, M.-C. (7) 106, 108 Labataiilc, P. (5) 60 Labhardt, A.M. (3) 65; ( 5 ) 178 Lachgar, M. (4) 159 Lachmann, J. (6) 49 Lacorte, S.(8) 139, 155, 156 Lacroix, M. (8) 147 Laege, M. (1) 494,498,500 Lagier, C.M.(8)50 Laguna, A. (1) 364; (6) 70 Lake, C.H.(1) 525 Lakhrissi, M. (4) 128; (6) 35 Lalonde, M. (1) 157 Lam, F. (1) 152 LambeU, A.-M. (4) 20 1 Lambert, J.B. (1) 352 Lambert, J.N. (5) 2 16 Lambertsen, T.(I) 274 Lammertsma, K. (1) 525 Lamp, D. (4) 22 Landini, D. (I) 403 Landis, C.R. (3) 94 Lane, H.P. (1) 180;(3) 21 Lane, T.M.(4) 240,300-302 Lanfranchi, M.(1) 373,374 h g , H.-F. (4) 83 Langc, P. (1) 141,235 Langer, F. (1) 280; (3) 25 Langer, RJ. (7) 246 Langer, RS.(7) 251,253,256 Langer,T.(1) 63 Langhans, K.P.(1) 153 Langlois,N. (4) 200 Langner, D. (5) 1 I7 Langner,R (1) 344 Lanza,T.J. (4) 99 Lapchenko, AS. (7) 257 Laplaza, C.E. (7) 81 Lappert, M.F. (I) 38,65

Larctina, A.P. (4) 49; (7) 8 Larpent, C. (1) 122 Larsen, E.( 5 ) 127 Lartiges, S.B.(8) 139, 142 Lashkari, D.A.( 5 ) 8 1 Laskos, E. (6) 37 Lassalle, L. (8)81 Lathourakis, G.E. (6) 5 Lattman, M. (3) 30 Lau, W.Y.(4) 146; (5) 22 Laurencin, C.T.(7) 249 Lomnt, C. ( I ) 484; (6) 20 Lam, W.H.G.(4) 137, 138 Lavcnot, L. (1) 122 Lavrova, E.E. (1) 298 Law, D.J. (7) 186 Law, S.J. (5) 235,271 Lawrence,N.J.(1)318;(6)69 Lay, L. (4) 210 L a m , R. (4) 203 Lc, Q.T.H.(1) 370 Lebeau, L. (1) 206; (4) 250; (7) 12, 13,48 Lebec, C. (5) 38 Lebl, M. (1) 203 Leblanc, J.C. (I) 105 Lecaer,J.P. (5) 255 Lecchi,P. (5) 263 Lecouvey, M. (6) 107 Lee, B.M. (7) 80 LCC,C.-W. (4) 110; (6) 97 Lee, D.W. (1) 300 Lee, H. (1) 243 Lee, H.F. (7) 128 Lee, H.4. (6) 34 Lee. J.-H. (2) 28 Lee, s. (1) 21 Lee, S.-J. (7) 244,245 Lee, X.P. (8) 126 Lefebvre, I. (3) 60 Le Flodr, P. (1) 567-569,572,573 LeGolvan, M.P. (7)267 Legoupy, S.(8) 8 1 Lehmann, C. (3) 65; (5) 178 Lchnert, R. (7) 58,157,158, 160 LeibGitz, D. (8) 15 Leikauf, E.(5) 73 Leininger, S.(I) 489,502 Lejczak, B. (4) 136,296 Lelievre, S.(1) 548 Le Maw, P. (1) 195 Le Menn,.C. (1) 126; (3) 96 Lemonovskii, D.A. (1) 104 Leng, F.F. ( 5 ) 209 Lenz,D.(2) 9 Lanard, G.A. ( 5 ) 23 1 Lequan, M. (1) 305

Author Itidex Lequan, RM. (1) 305 Lequeux, T.P.(4) 127,160,161, 170;(6)85 Lemer, RA. (4)68 Letsingcr, RL. (3)80;(5) 171, 176,177,204 Leumann, C. (5) 144 Leung, K.-H. (8)97 Leung P.-H. (1) 265,266,547, 549 Leung W.-P. (1) 38 Lcupin, W. (3) 65;(5) 178 Le Van, D.(1) 494,498,500 Levelut, A.M. (7)98 Lever, D.C.(3)56 Levina, L.V. (1) 121 Lcvitcs, F.A. (7) 163 Levon, V.F. (4) 117 Levscn, K. (8)133 Levson, S.M. (4)300 Levy, S.G. (5) 24 Lewis,N.J. (1) 187 Lewtas,J. (8) 152 Lezius, A. (5) 247 L’Hostis-Kcrvclla, I. (4)158 Li, A.-R (4) 120 Li, C. (4) 171,225 Li, C.-W. (4) 166 Li, C.Y. (7)128 Li, D.-G. (8)83 Li, G. (8)51 Li, H.(5)59 Li, J. (8)118 Li, J.-S. (7) 182 Li, R (1) 427 Li, T.(4)68 Li, Y.-C. (4)34 Li, Y.F.(5)227 Li, Y.-G. (4) 169;(8)65 Li, Y.-M.(4)34 Li, Z.(4)132 Li, Z.-M. (4) 147 Liang, M.(7)228 Liang, X.L. (5) 242 Lianis, P.S.(6)37 Lianza, F. (1) 116 Liddie, J. (1) 3 18;(6)69 Liebman, J.F. (I) 564 Lightfoot, P. (4)30 Lin, J. (7)67;(8) 121 Lin, S.J. (8) 127 Lin, T.Y. (4)99 Lin, Y. (8)87 Lm,Y.H. (5) 242 Lmdblom, L. (8)48 L d e , S.(5) 157 Lindunan, S.V.(8)69

373 Lindcnberg, F. (1) 110 Lindncr, E. (1) 109 Lindsay, S.M. (5) 234 Liou, K.-F. (1) 171,172 Lipka, P.(5) 13 Lipkovski, Y. (8)112 Lipkowitz, K.B. (7)90 Lipkowski, J. (4)14 Lippert, B.(5) 166 Liquier, J. (5)206 Litinas, K.E. (6)5 Litten, J.C. (5) 144 Litvinov, I.A. (4)3 1 1 Liu, B.-J. (1) 152 Liu, D.Y.(5) 80 Liu, H.-Y. (8)44 Liu, J. (8)65 Liu, K.(2)9 Liu, L. (4)3 15;(8)5 1 Liu, L.K. (1) 358 Liu, Q.-T.(1) 47 Liu, RH.(5) 62 Liu, S.T.(1) 56 Liu, S.Z. (4)63 Liu, W.-Q. (4)21 1 Liu, X.H.(5) I5 Liu, X.-L. (4) 169 Liu, Y.-H. (3) 23;(4)232 Liu, Z.J. (4)71 Livantsov, M.V. (2) 12-15;(4) 216,217 Livantsova, L.I. (2)14 Livinghouse, T.(1) 40 Ljanage, S.S.(1) 156 Llamas-Botia, J. (1) 225;(7) 15 Lloyd, D.H.(5)I10,111 Lo, L.-C. (4)68 Loakes, D. (5) 157,158 Lobana, T.S.(1) 381 Lobanov, D.I. (1) 353 Lochon, P.(7)226,286 Loeber,C.(1)319 UMbCfg, H. (3) 61,74 Locw, A. (7)78 Logunov, A.P. (1) 357 Loh, S.-K. (1) 549 Loh,V.M., Jr. (3) 10,12;(4)113 Lohray, B.B.(4)206 Lombarado, G.M.(7)90 Long, J. (1) 8 Longato, B.(1) 363 Longeau, A. (1) 280;(3) 25 Lonnbcrg, H. (5) 16,35,46,64 Upez, S.(6)110 Lop-Leonardo, C. (1) 225;(7)I5 Lopez-orti~,F. (7)4,39,93,183; (8)67

topusiriski, A. (4)230 Lora, S. (7)243 Lorcnts, K.-L. (2)12;(4)216,217 Lorcntzon, J. (1) 565 Lork, E. (7)101, 102 Losicr, P. (1) 512 Loskutov, V.A. (4)247 Lough, A.J. (1) 3 1; (4)304;(7) 175,212 Lowe, C. (4)58 Lowe. G.(4)41 ;(5) 26 1 Loy,D.A. (1) 507 Lozinskii, M.O. (5) 168;(8) 12 Lu, L. (6)43 Lu, R (8)66 Lu, RJ. (8)44 Lu, X.Y.(1) 173,316;(4) 107, 108 Lu,X.Y.(1)317;(4) 109 Lu, 2.(4)244 Lube, M.S. (1) 96 Lubell, W.D. (4)205 Lubman, D.M. (5) 242 Lu&, 1.-L. (4) 178 tuczak, L. (4)230 Ludanyi, K. (1) 128 Ludcma, K.C. (7)147 Ludeman, S.M. (5) 220 Ludvik, J. (1) 160 Luhrmann, R (5) 169 Lukashev, N.V. (1) 472,473;(3) 102;(7)30-34 Luo. H. (1) 10 Luzikov, Yu.N. (2)12,14;(4)91, 216,217 Lysenko, K.A. (1) 338,353 Lyubchcnko, Y. (5) 234 tyzwa, P. (4)183 Ma, C.L. (1) 317;(4)108, 109, 244 Ma, F.P.(4)227 Ma, X.-B.( I ) 197 Ma, Y.X. (1) 317;(4)108. 109, 244 McAuleybecht, K.E.(5)23 1 McAuliffc, C.A. (1) 180;(3) 21 Maccioni, A. (7) 1 1 1 Mwioni, E. (7)1 1 1 McClain, M.D. (1) 507 McCloskey, J.A. (5) 222,260,261 McClure,’C.K. (2)8;(4)280,281 McDonald, M.A. (1) 67 McDonald, R (2)29;(7)67;(8) 55

McEldoon, W.L. (5)26

3 74

McElroy, A.B. (1) 327; (6) 62 Macfarland, D.K.(3) 94 McFarlane, W. (1) 266 McGeorge, G. (8) 50 McGhce, W.D. (7) 53 McGrath, J.E. (1) 129 Macgregor, S.A. (7) 191 McGuigan, C. (5) 1,2,5 Machado, R (1) 54 1 Machiguchi, T. (1) 4 18 McKec, M.L. (1) 89 McKenna, C.E. (4) 147, 167, 168 McKeown, N.B. (6) 115 McKervq, M.A. (1) 320 Mackewitz, T.W. (1) 454,484, 485,489; (8) 22,24 McKinstry, L. (1) 40 McLaughlin, L. W. (5) 103- 105, 161,208 M c h a n , G.D.(1) 117 McMinn, D.L.(5) 185 McPartlin, M. (I) 429 McQuire, L. (4) 104; (6) 81 Madaule, Y. (7) 36 Maeda, H. (1) 396 Maejima, T. (7) 271,279 M&M, G. (I) 149,441,442 Maertens, C. (6) 131 Maven, U. (6) 22 Maffei, M. (4) 142 Magdeeva, RK. (3) 33 Maggio, F. (1) 347 Magill, J.H.(7) 264,265 Magomedova, N.S. (2) 5; (3) 36, 46; (4) 318 Magull, J. (7) 75, 177 Mahieu, A. (1) 528 Mahmood, N. (5) 34 Mahmoudkani, A.H. (4) 59 Mahon, M.F. (1) 189,505; (7) 68 Mai, H.J. (7) 75,176,179, 181 Maier, L.(3) 5; (4) 176,218; (8) 30 Maigrot, N. (1) 573 Maina, T. (1) 142 Maiorova, E.D. (4) 246 Maitre, L. (3) 5; (4) 218 Maiya, B.G. (8) 37 Maji, D.K. (4) 206 Majoral, J.-P.(1) 138, 140,245, 297,528; (4) 234; (7) 22,79, 120 Majzner, W.R. (1) 355 Mak, T.C.W. (1) 358 Maki, T. (1) 396 Makino, K. (3) 52; (5) 94,219 Maksimov, A.S. (7) 163

OrganophosphorusChemisty Maleknia, S.D. (5) 252 Malenko, D.M. (2) 10 Malenkovskaya, M.A. (3) 46; (4) 318 Malet-Martino, M.-C. (8) 38 Mali, R S . (6) 126 Malik, K.M.A. (1) 482 Malisch, W. (1) 107,516-519 Mallakpour, S.E.(7) 21 1 Malmstttim, T. (1) 145 Malone, J.F.(1) 320 Maloney, J.D. (1) 99 Maly-Schreiber, M. (7) 280 Malysheva, S.F.(1) 87, 119, 120, 350 Mamatyuk, V.I.(4) 247 Manetsberger, RB. (1) 7 Mann, M. (5) 250 Manncrs, I.(1) 3 1; (7) 175,208, 212,215,228 Manou~y,E. (1) 30 Mansour, T.S.(5) 3 1 Manthey, M. (I) 174 Mantick, N.A. (5) 88 Manuel, G.(1) 36,288 Manzhukova, L.F. (3) 40 Manzo, P.G. (1) 8 1 Manzur, J. (I) 541 Mao, B. (5) 223 Marcantoni, E. (6) 60 Marchetti, M. (1) 80 Marecek, A. (7) 133 Marescaux, C. (3) 5; (4) 218 Margcrum, L.(7) 107 Maria, P.-C.(7) 7 Marinctti, A. (1) 126.46 1;(3) 96 Markovskii, L.N. (1) 295; (4) 14, 16, 19,20; (8) 112 Marque, S.(1) 264 Marrs, D.J.(1) 320 Miirsault, E.(3) 55 Marsch, G.A. (8) 153 Marsilio, F. (7) 243 Martelletti, A. (I) 29 Martelli, G. (3) 14; (4) 133, 134 Martens, J. (4) 180, 190; (8) 32 Martens, R (1) 237 Martens-von Salun, A. (2) 24 Martin, A. (I) 154 Martin, G. (1) 430 Martin, L.B.(5) 237 Martin, N. (6) 130 Martin, P. (5) 91 Martin, S.A. (5) 238,243,248, 249,268 Martineq E. (1) 134, Martino, R (8) 38

Marvin, W.B. (5) 106 Marzilli, L.G. (1) 365 Marzilli, P.A. (1) 365 Masamune, S.(6) 75 Maslennikova, V.I.(3) 32 Maslova, R N . (5) 241 Masojidkova, M. (5) 28-30,49 Mass& H.-C. (7) 178 Massa, W. (7) 70,71,176,179 Massey, J. (7) 228 Masson, S.(6) 94 Massonszymczak, A. (1) 26 Masterman, T.C. (1) 417 Mastryukova, T.A. (1) 338,353 Masuda, H. (1) 190,191 Matcm, E. (1) 72.73 Matevosyan, RO. (7) 110 Mathcy, F. ( I ) 461,463,488,524, 539,545,546,548,554, 567-569,572,573 Malhieu, R (I) 54 Mathur, P. (1) 504 Matrosov, E.L. (1) 3 14; (7) 19 Matsuda, A. (5) 8,82 Matsuda, Y. (I) 574 Matsui, M. (1) 370 Matsumoto, A. (7) 140 Matsumoto, K. (4) 141, 196; (6) 3 Matsumoto, Y.(4) 75; (5) 125, 126 Mntsuo, Y. (4) 24 Matsuoka, H. (7) 164 Matsushita, Y. (6) 123; (7) 4 1 Malsuzaki, T.(6) 106 Matt,D. (1)319 Matteson, K.J.(5) 268 Matteucci, M.D. (5) 52,129 Mattieu, A. (7) 79 Mattingly, P.G. (3) 78 Mattner, M. (1) 52 Matulicadamic, J. (5) 137,197 Mahwzv, S.V.(1) 3 14 Matveeva, A.G. (1) 314; (7) 19 Matyjaszcwski, K. (7) 16,217, 2 18,263-265 Maupriveq 0. (1) 320,321 Maury, C.(3) 9; (4) 193; (5) 60 Mauthe, RJ. (8) 153 Mawhinney, T.P. (8) 145 Maya, H.A. (1) 15 M;lzcrolles, P. (I) 484 Mazhar-ul-Haque, (4) 300 Maziefez, M.R (7)36 Mazumder, A. (5) 165 Maukiewicz, R (1) 181 Mazzi, U. (1) 142 Mauuca, D.A. (7) 28,29

AufhorIndex Miller, T.J.(5) 88 Mills, S.G. (4)99 Milone, L. (8) 16 Milstein, D.(1) 60 Mima, H. (1) 68;(8)49 Min, C. (6) 113 Minami, T. (1) 5 1; (4)173 Mingazova, B.F.(4)236 Minko, S.V. (4)217 Minto, F. (7)235 Mioskowski, C. (1) 206; (4)250; (7)12, 13,48 MU, 0.(2)19 Mirelis, P. (5) 10 Mirkin, C.A. (1) 85; (3) 80;(5) 204 Mironov, V.F. (2) 1 1 Mirza-Aghayan, M. (1) 36 Misaki, Y.(6) 128 Mishchenko, N.I. (6)39 Misiura, K. (5) 92,93 Mitchell, G.E. (7) 142 Mitchell, H.J. (1) 329;(6)58,63 Mitchell, M.C.(3) 89;(4)13 1 Mitchell, T.N. (1) 323 Mitjaville, J. (4)234;(7)120 Mitrasov, Yu.N. (4)88,89 Mitsui, T. (5)145 Mitsusada, S.(7)85 Miynbc, H.(I) 4I6 Miyakc, S.(1) 233 Miyamoto, M. (4) 173 Miyashita, K. (1) 416 Miyoshi, K. (1) 5 11; (4)35 180 Mizuguchi, M. (3) 52;(5) 94 Mezzetti, A. (1) 1 16 Mizusaki, H. (7)95 Miao, F.-M. (4) 169 Mizuta, T. (1) 5 I 1 Michalska, M. (4)44 Mlotkowska, B.(3)71 Michalski, J. (3) 84;(4)54,230 Modrich, P. (5)220 Michel, J. (5)159; (7)280 Modro, A.M. (4)143,257,298 Michels, G.(1) 484 Modro, T.A. (1) 429;(4)64,67, 102,143,257,272,273,298 Mickel, S.J. (3)4,s;(4)218,219 Middleton, P.J. (5) 139 Mocller, M. (7)49,54 Miekisch, T. (7)75 Moezzi, A. (1) 69;(8) 96 Mieloszynski, J.-L. (4)42,43,74 Moghaddas, S.(5) 216 Mikhailopulo, I.A. (5) 147,170 Mogi, S.(7)156 Mohammadi, S. (5) 206 Mikhel, I.S.(2)3 Mikolajczyk, M. (1) 355,382-384; Mohan, T.(1) 230;(8) 150 (4)183;(8) 92 Moise, C. (1) 105, 106 Mikoluk, M.D. (7)77 Mok,K.F. (1) 265,547,549 Milecki, J. ( 5 ) 168 Molchanova, G.N. (4)49 Milewska, M.(4)179 Moldovan, 2.(7)9 Millar, J.G. (6)112 Molenbcrg, A. (7)54 Miller, J.M.(1) 268,428 Molina, C.(8) 154 Millcr, P.C. (4)278;(6)92 Molina, P. (1) 225;(6)124;(7) 15, 44 Miller, P.S. (5) 160 Moll, M. (1) 499;(7)26, 192 Miller, R W . (8)23 Medvedeva, L.Ya. (7) 139 Meervelt, L.V. (6)39 Mectsma, A. (7)124 Meeuwenoord, N.J. (3) 86,88 Mchrotra, A.P. (6)45 Meier, C. (4) 137, 138;(5) 4,32, 33,247 Meijer, E.W. (1) 361;(8)89 Meisel, M. (8) 100 Meliet, C. (3)95 Melillo, D.G.(4) 15 1 Melillo, V. (3) 5; (4)218 Melius, C.F. (5) 220 Mclnicky, C. (2)22.24 Melvin, O.A. (1) 48 Memeger, W.,Jr. (7)50 Meng, B.(5) 122 Menke, C. (1) 405 Mentz, M. (4)64,67 Menyhard, D. (1) 575;(4)239 Merchant, T.E. (8) 17 Mercier, F. (1) 488,548 Merckling, F.A. (4)62 Mergny, J.L. (5)207 Merkulov, A. (1) 284 Mernyi, A. (1) 22 Meshkov, S.V. (8) 45 Mesilaakso, M. (8)20 Metzler, M.D. (5) 189 Mcunicr, B.(5) 193 Mews, R (7) 101, 102 Meyer, C.N. (7) 103 Meyer, H.A. (1) 109 Meyer zu Kiicker, R (7)74,75,

375 Molloy, K.C. (1) 189;(7)68 Moloy, K.G. (3) 26 Momchilova, S.(1) 367 Mondadori, C. (3) 5; (4)218 Monforte, P. (1) 263;(4)3 10;(8) 109 Monroc, S.(1) 209 Montague, R A . (7)217,218 Montchamp, J.-L.(3) 7 Montero, J.-L.(4)208 Montoneri, E. (4)263 Monyague, R.A. (7)263 Moock, K.H. (7)191 Moon, M.R (7)245 Moore, J.L. (6)41 Moore, W.(4)256 Moosavimovahedi, A.A. (5) 37 Moothe, V.K. (8) 117 Moralcs, E.(7)268-270 Moravek, J.F.(5) 220 Moreau, S. (5) 159 Moreau-Bossuet, C. (I) 30 Morcllo, M. (8) 143 Morcno, J.-M. ( I ) 1 80;(3)21 Morgan, T.A. (7) 141,145, 147 Mori, H. (6)128 Mori, S.(7)46 Mori, T. (6) 128 Moriarty, R.M. (2)9 Morikawn, T.(7)287 Morin, G.T. (5) 6 Morila, D.K. (1) 252 Morita, H. (4)75 Moriya, K. (7)95-98 Moro, G.L. (6)23 Momssey, C.T. (7)215 Morse, J.G. ( I ) 300 Mortrewr, A. (3) 95,98 Morvan, F. (5) 120,130,131 Moscherosch, M. (1) 436 Moser, H.E. (5) 91,252 Moss, S.(1) 158 Mothcrwell, W.B. (4)124 Motoyoshiya, J. (6)79 Mouchet, P.(1) 326,413 Mountford, P.(1) 104 Moureau, L. (2)20 Mphahlele, M.J. (4)272,273 Muang, W . 4 . (8)42 Much4 A. (4) 197,223 Muci, A.R (1) I5 1; (6)56 Mucic, RC. (3) 80; (5) 204 Muller, A. (1) 405;(6)18; (7)64 Miiller, G. (6)49 Mucnchenbcrg, J. (8)57 Mugnier, Y.(1) 159 Mukai, H. (1) 4I; (3) 11

OrganophosphorusChemistry

376 Mulhearn, D.C. (1) 452 Mullah, B.(5) 85 Mullane, M.V. (I) 187 Muller, C. (1) 295 Mdler, E.L. (4) 143 Muller, J.G. (5) 226 Muller,RK. (1) 157 Muller, U.(1) 404 Mulliez, M. (4)8 1 Mulvaney, A.W. (1) 20 Munik, S.N. (4)53 Munoq A. (4) 178 Muralidhara, M.G. (7) 105 Murata, K.(7) 156 Murray, A.W. (1) 342;(4)104;(6) 64,81

Murray, J.B. (5) 167 Murtuza, S. (1) 61 Musier-For+, K.(3) 20;(5) 96 Musin, R.Z.(1) 177,242 Mustakimov, E.R (I) 176,177 Muth, A. (1) 58 Muth, J. (5) 247,271 Muzzalupo, I. (5) 233 Myahara, S.(7) 155 Myata, Y.(7)291 Myer, C.N. (7)103 Mynott, R (1) 502 Naan, M.P. (1) 222 Nachtigal, C.(1) 407 Nadano, R.(2)30 Nader, B.S.(7)141, 143 Nadji, S.(5) 218 Nagai, K.(5) 229 Nagalakshmamma, M. (4)36;(8) 31 Nagar, P.N. (8)64 Nagashimq H.(8) 158 Nagata, A. (7)152 Nagata, K.(1) 44 Nagino, C.(1) 213;(6)30 Naidu, S.M. (4)7, 11,3 19 Naiini, A.A. (2)28 Naito, K. (7)290 Nakabayashi, N. (4)141 Nakagawa, S.(7)96 Nakai, K.(7)277,278 Nakamura, A. (5) 174 Nakamura,E.(1)41;(3) 1 1 N a k a ~ n ~M. ~ a (4) , 55-57 Nakanaga, T. (7)84,275-279 Nakano, H. (5) 145,146 Nakayama, T.(7)153 Nakazawa, H.(1) 5 1 1 Namestnikov, V.I. (4)237

Nandaran, E. (4)206 Napicraj, A. (4)76 Napierala, M.E. (7)232,233 Nashn, J.B. (1) 429 Naso, F. (6)80 Nasonova, N.S. (1) 178 Naumov, V.A. (1) 302;(4)3 1 1 Navratil, 0. (7)198 Nayyar, N.K. (4)3 10 Neda, I. (I) 351; (2)22-24;(4)21, 308,309;(8)32,38 Nedolya, N.A. (7) 122 Nefedov, O.M. (1) 166,446 Neganova, E.G. (1) 55, 178 Neidle, S.(5) 205 Neidlein, R (4) 162 Neidlcin, U.(4)13 Nelson, A. (1) 328;(6)61 Nelson, C.J. (7)223,224,273 Nelson, D.A. (7)285 Nelson, J.H. (1) 244,550,551; (8) 84 Nelson, J.S. (5) 171, 177 Nesterov, V.Yu. (1) 302 Nesterova, L.I. (2)10 Nethaji, M. (8) 47 Ncumann, B. (I) 438,462,464, 465,509,557 N m u l l e r , B. (6) 18;(7)64,181 Neuner, P. (5) 186 N m a n , P.D. (1) 359;(6)55 Ng, S.W. (1) 368 Ngo, D.C. (7)92,114,297 Ngoh, M.A. (8)130 Nguyen, C.H. (5)206,207 Nguyen, M.T. (1) 453 Ni, J. (1) 428 Ni, J.S.(5) 261 Ni, Y.(7)175,212,228 Nichioka, T. (8)49 Nicoara, S.(7)9,72 Nicolaou, K.C.(6)132 Nicolini, M. (1) 142 Nicotra, F.(4)210 Niecke, E.(1) 77,434,447,455, 471,535,537;(3) 104;(4)312; (6)14, 17;(7)78,293;(8) 1 I, 27 Niedzwiecki, L.M. (4)99 Nief, F. (1) 102 Nieger, M.(I) 77,447,455,471, 5 10,520,535,537;(4)312;(6) 14, 17,48;(7)78, 166,293;(8) 27 Niclsen, C. (5) 143 Nielsen, J. (5) 202 Nielsen, K.D.(5) 141 ,

Niclsen, P.E. (5) 1 15, 116,118 Niemcyer, M. (1) 71 Niemeyer, U.(2)24;(8)38 Nieschalk, J. (4)154,155 Nieuwenhuizen, P.J. (1) 566 Nifant'ev, E.E.(3) 32,33,36-38, 40,41.4649;(4)318,322;(8) 45,108.1 I 1 Nifant'cv, E.I. (3) 35.40; (4)235 Nigro, C. (5)233 Niizuma, S.(1) 123 Nikogosyan, L.L. (7)110 Nikolaev, V.A. (1) 229;(7)18 Nikonov, G.N. (1) 104,176,177, 242,289 Nishi, M. (5) 219 Nishibayashi, Y.(1) 19,28 Nishida, T. (4)33 Nishhwa, Y.(8) 140 Nishio, K. (7)272 Nishioka, T.(1) 68 Nishioka, Y.(7)154 Nissan, J.S. (1) 207 Nitta, M. (7)46 Nixon, J.F.(1) 479,503405,552, 553,555,558 N i m o v , I.S.(4)45-48;(8) 82 Nkrumah, S.(I) 62 Nobuki, S.(1) 233 Node, M. (6) 106 Noth, H.( 1) 239,292,423,441, 449;(6) 10, 12;(8)25,26,110 Noguchi, H. (6) 136 Noguchi, T.(7)290 Nolkmeyex, M. (1) 519 Nome, F.(1) 348 Nomizu, M. (4)35 Nomura, S. (7)152 Nordhoff, E.(5) 240,247 Norgrcn, RM. (5) 81 Norton, J.R (1) 252 Noh, H. (1) 89,149 Nournan, M. (7)198 Nouri-Sorkhabi, M.H. (8) 19 Novak, L. (1) 21 1,212 Novikova, O.P. (2) 13, 14 Novikova, O.V. (1) 341 Novikova, Z.S. (1) 167;(4) 112, 260 Novosad, J. (1) 378;(7)206 Nowalinski, M.(1) 216;(4)174 Noyori, R (4)205 Nozhevnikova, E.V. (3) 75 Nunez, R (I) 238 Nunn, C.M.(1) 93 Nupponen, H.(4)255 Nurkulov, N.N. (3) 47

Author Index Nyulaszi, L. (1) 544 Oae, S. (1) 2 Obafmi, C.A. (7)20 Obika, S.(5) 125,126 OBrien,P. (1) 33 1,332;(6)52, 54,59 Ochoa de Retana, A.M. (4) 118 OConnor,S.J. (7)233,237 Odinets, 1.L. (1) 338 Oechsner, H.P. (1) 422;(2)7;(6)

11 Oefele, K. (1) 253,254 Ochl, RS.(4)226 Oehler, E. (4)194 Ochmc, G. (4)199 Ofengand, J. (5)260 Offensperger, W.B.(3) 83 Ogawa, H. (7)15 1 Ogct, N. (4)77 Oguri, M.(1) 213;(6)30 Oh,D.Y.(4)103,110,166,269; (6)97 O'Hagan, D.(4)154,155 OHagan, P. (1) 320 Ohaus, G. (8)2 Ohba, H. (1) 233 Ohe, K.(1) 19,28 Ohmori, H.(1) 396 Ohms, G.(1) 198;(4)293,316, 320 Ohno, A. (1) 24,270,349;(3) 107 Ohno, F. (6)83 Ohsugi, Y.(5) 126 Ohta, A. (6) 127 Ohta, H. (1) 418;(6)32 Ohta, Y. (4)274;(6) 90 Oivanen, M.(5) 16,35,46 Okabe, M. (1) 2 Okabe, Y.(7) 154 Okada, Y.(1) 51;(4) 173;(7)154 Okamoto, Y. (4)55-57 Okano, T. (6) 135 Okauchi, T.(1) 5 1 Okawa, T.(6) 122;(7)47 Okazaki, R (2)21;(4)285;(6)21, 83 okita,s.(7)164 Okruszek, A. (4)60,317;(5)92, 100

Okuma, K. (1) 418 O h u r a , T.(8) 140 Olagnon-Bourgeot, S.(4)291 Olbrich, F. (1) 497 Olcjnik, A. (7)116-118 Olejnik, J. (3)63,71;(5) 184

377 Oliver, A.G. (3) 8;(4) 3 13 Olivicr, A. (3) 3 1 Olivicri, A.C. (8)50 Olmstead, M.M.(I) 69;(8)96 O l p ~H.-R , (3) 4,5;(4)218,219 Olsen, G.M.(1) 395 Olshavsky, M.A. (7)222 Olson, W.K. (5)232 Ono, A. (5) 82 Ono,M.(1)418 om,s.(4)75 Onoda, T.(6)114 Oosugi, T.(7)152 Oprits,Z.G. (7)161 Opromolla, G.(1) 267 Or4 M.(5) 16,35,46 Ordoukhanian, P. (3)64 Orduna, J. (6)130 Oretskaya, T.S.(5) 183 Orgel, L.E.(5) 62 Oji, C.C.(4)80 Orlov, V.M.(5) 241 Orlova, L.A. (7) 163 ORourke, S.S. (1) 210 Orpen, A.G. (1) 154,155 Orvig, C.(1) 10 Onhekovskaya, E.I.(3) 47 Oshikawa, T. (8)62,63 Osowaska-Pacewicker, K. (7)38 Ostrowski, A. (1) 540 Otaguro, T.(1) 51;(4)173 Otaka, A. (4)35 Otsubo, K. (6)76,77 Otvos, L. (5)109 Oubridge, C. (5) 229 Owyupin, A.B. (4)60 Ovasapyan, V.A.(7) 110 Ovchinnikov, V.V.(4)282;(8) 164 Oyarzabd, J. (4)1 18 Ozaki, F. (1) 214;(6)29 Ozaki, H.(5) 174 Ozaki, S.(3) 108;(4)40

Palcnik, G.J. (7)3 Palm, M.(7)268 Pan, Y.Q.(5) 1 1 1 Pandey, S.K.(7) 190 Pandolfo, L. (6)38 Pandurangi, RS.(7)66 Panigrahi, G.B.(5) 187 Panina, E.V.(3) 32 Pankicwicz, K.W. (5) 13 Pannell, L.K.(5) 263 Panunzio, M.(3) 13,14;(4)133, 134,204 P a t q L. (4)210 Pappalardo, G.C.(7)90 Papsucv, M.Yu. (2)12 Paquer, D.(4)42,43,74 Parish, RV. (1) 159 Park, C.E.(7)288 Park, H.M.(8)123 Park, J. (1)21;(6)113 Park, J.-A. (7)244,245 Park, K.M. (6)1 1 1 Park, P. (7) 228 Parks, M.E.(5)210 Parlevliet, F.J. (3) 3 1 Pany, J.S.(1) 103 Parsons, s. (1) 495 Parvez, M. (7)65,114,173,174, 297;(8) 113 Passmorc, J. (1) 495 Pastex, M.D.(7)53 Pastera, P. (7)133 Pastor, A. (6) 124;(7)44 Patel, D.J. (5) 223 Patel, D.V.(4)212,226 Patel, G.(4) 125 Patel, R (5)173 Pathak, D.D.(1) 90 Patil, V.J. (6)22 Patin, H.(1) 122 Palois, C.(4)253 Patsanovskii, 1.1. (7)6;(8)92,115 Patsiouras, H. (1) 204 Paul, F.(1) 554 Paul, M.(1) 394;(8)46 Pauli, J. (4)58 Paasch, K. (1) 447 Paver, M.A. (1) I 13 Paasch, S.(7)94 Pabel, M.(1) 67,90,132,275,276 Pawloski, C.E.(7) 141 Paync, L.G.(7)252-254 Pace, P. (4)106 Padros, E. (6)110 Payrastre, C.(7)36 Page, P. (4)144 Peacock, RD. (1) 359;(6)55 Pearce, D.A. (5) 216 Paine, RT.(1) 239,306,515 Pcbler, J. (7) 180 Pakula, T.(7)263 Palacios, F.(1) 334,336;(4)118; Pedersen, E.B.(5) 127 Pedroso, E. (3)69 (6)66,67;(7)45 Pcer, M. (1) 63 Palacios, S.M.(1) 81 Palchun, V.T. (7)257 Peeters, O.M.(4)201

OrganophosphorusChemistry

3 78 Pegoretti, A. (7) 235 Pegram, J.J. (6) 112 Peiffer, G. (4) 142 Pelaet-Arango, E. (7) 4,93, 183; (8) 67

Pelemans, H. ( 5 ) 5 Pelicano, H. (5) 60 Peltier, J.M. (5) 260 Pemberton, L. (7) 130,234 Peneory, A.B. (1) 82 Pcn’kovskii, V.V. (1) 456 Pennington, W.T. (1) 97,98 Penso, M. (1) 403 Pcrbost, M. (5) 120 Percival, K.J.(3) 50; (5) 180 Percy, J.M. (4) 127, 160, 161, 170; (6) 85

Perera, S.D. (1) 13, 135-137 Peresypkina, L.P.(4) 92 Perettie, D.J. (7) 145 Perez-Carreno, E. (7) 183 Pcrich, J.W. (4) 61 Perie, J. (4) 144 Perigaud, C. (3) 60; (5) 3 Perin, G. (6) 140 Peris, E.(1) 345 Pestana, D.C.(1) 69; (8) 96 Pestov, N.B. (3) 75 Peters, E.M. (1) 324; (8) 29 Peters, K. (1) 324; (8) 29 Peters, W. (4) 292 Petersen, G.V. (5) 124 Petersen, J.L. (3) 26 Pcterscn, K.H. (5) 1 18,202 Peterson, E.S.(7) 284 Peterson, M.A. (5) 5 1 Petnehazy, I. (8) 116 Petnisevich, K.M. (8) 115 Petrillo, E.W.(4) 226 Petrov, A.A. (3) 79; (5) 20 1 Petrov, M.V. (8) 41 Petrova, J. (I) 367 Petrovskii, P.V. (I) 338; (4) 49,60 Petrucci, M.G.L. (1) 148 Petyak, M.E. (4) 69 Peukert, S. (1) 234 Peukert, U. (8) 85 Pevzner, L.M. (4) 96,97 Peyman, A. (5) 188 Pfeiderer, W. (5) 9 Pfister, H. (1) 518 Pfister-Guillouzo, G. (1) 435 Pfitzncr, A. (1) 76,529 Pfleidew, W. (3) 70; (5) 136, 147, 165

Pham, P.T. (5) 14 Pham, T. (4) 205

Phillips, B.W.(4) 256 Phillips, L.R (5) 133, 134 Phillips, S.H.( I ) 134 Phillips, S.J.(5) 151 Pianka, M. (8) 48 Pieken, W.A. ( 1) 2 10 Pieles, U. (5) 252 Pienaar, A. (4) 257,273 Pierloot, K. (1) 453 Pierre, J.L. (6) 138 Pierwocha, A.W. (1) 181 Pietroni, B.R (4) 106 Pietrusiewicz, M.K. (1) 245,307, 347; (7) 79

Pielschnig, R. ( I ) 434; (3) 104 Piettre, S.R(4) 123,228,229, 268; (6) 87

Pikl, R (8) 101 Pilard, J.F. (1) 130 Pilkington, M.J. (4) 3 14 Pillct, N. (5) 158 Pilloni, G. (1) 363 Pilotek, S.(1) 556 Pinchuk, A.M. (1) 282,284,295 Pinchuk, V.A. (1) 295 Pinkus, A.G. (4) 80 Pintauro, P.N. (7) 237 Piquct, V. (1) 223; (7) 25 Pirkle, W.H.(8) 149 Pirozhenko, V.V. (2) 10; (4) 14, 16,19,20

Pirrung, M.C.(3) 56; (5) 23,77 Pisarcvskii, A.P. (1) 177 Pivozhcnko, V.U.(8) 112 Pla, F.P. (6) 33 Placha, K. (7) 1 18 Plack, V. (1) 241 Plank, S.(1) 476,478; (3) 44, 101; (6) 15

Plate, N.A. (7) 261,262 Platanov, A.Yu. (4) 246 Plalts, J.A. (1) 256 Plalzer, N. (7) 197 Plenat, F. (1) 385; (4) 197; (7) 23, 100

Plinta, H.-J. (4) 309 Podda, G. (7) 111 Podkopacva, T.L. (5) 170 Podlaha, J. (1) 160 Pijtschke, N. (1) 47 1 Pogosyan, A.A. (7) 110 Pohjale, E. (4) 255 Pohl, D. (1) 499 Pohl, S.(1) 237 Poitras, M. (4) 28 Polborn, K. (1) 478; (3) 44 Polezhaeva, N.A. (4) 165; (8) 10

Pollkarpov, Yu.M. (1) 3 14; (7) 19 Polimbctova, G.S. (8) 94 Polo, S.A. (4) 99 Polovinko, V.V. (1) 470; (7) 5 Polucci, P. (5) 205 Polushin, N.N. (5) 138,192 Pommier, Y.G. (5) 165 Pompon, A. (3) 60 Pon, RT. (5) 22 1 Pons, M. (6) 33 Popov, A.F. (7) 109 Porter, K. (5) 59 Portmann, S.(5) 54,230 Porwolik, 1. (7) 1 16,118 Poschenriedcr, H. (7) 42 Posner, G.H. (6) 135 Potaman, V.N. (5) 21 1 Potrzebowski, M.J. (4) 305; (8) 56 Potter, B.V.L. (4) 22,26,27 Pottcr, G.E. (7) 147 Povolotskii, M.I. (1) 470; (7) 5 Powvcll, RJ. (1) 93 Powell, RL. (1) 222 Power, G.A. (6) 115 Power, P.P. (1) 69,91; (8) 96 Powolk, I. (7) 117 Powroznyk, L. (1) 429 Po-, M.F.(3) 5; (4) 218 Pragnacharyula, P.V.P. (4) 145; (6) 108

Prkash, C. (6) 119 Prakash, T.P. (5) 175 Prakasha, T.K.(2) 16 Pratvicl, G. (5) 193 Prechtl, F. (1) 107; (6) 50 Predieri, G. (1) 373,374 Predvoditclev,D.A. (3) 46; (4) 3 18 Prectz, W. (1) 407 Pregosin, P.S. (1) 165 Prescott, S.(1) 209 Presnell, M. (1) 207 Previale, L. (8) 143 Prevote, D. (1) 297 Price, D.A. (1) 337; (6) 57 Price, S.R.(5) 229 Priebe, W. (5) 209 Priermeier, T. (1) 52,366 Principato, B. (4) 142 Principato, G. (8) 149 Prishchenko, A.A. (2) 12-15; (4) 216,217

Pritchard,,RG. (1) 180; (3) 21 Pritzkow, H. (I) 39,53,78,100, 468,469; (6) 9; (8) 68

Probert, M.A. (4) 152 Probst, M.F. (4) 102 P r o k h o d o , LA. (3) 75,79; (5)

Author Index 20 1

Prosvirkin, A.V. (8) 10 Provent, C. (6) 138 Prpi, M.S. (7) 99 Przcwloka, T. (5) 209 Pucher, S.R.(7)247 Pucknat, H. (1) 494 Pudovik, M.A. (3) 39; (7) 27 Puke, C. (6) 20 Pulst, S.(1) 25 1 Puranik, D.B.(1) 556 Purchase, C.F. (1) 2 19 Pustobaev, V.N. (5) 24 1 Pyzowski, J. (5) 102 Qi, M. (4) 265 Qiu, W. (4) 122 Qu, G. (8) 138 Quagliariello, C. (5) 233 Quaglino, P. (8) 143 QuasdortT, B. (1) 464 Quast, H. (4) 52 Que, L. (1) 362 Quin, G.S. (1) 532; (4) 287 Quin, L.D. (1) 308,475,532,533, 575; (3) 100; (4) 84,239,287

Raab, U. (8) 128 Raabe, G. (1) 14 Rabe, G.W. (1) 101 Rabiller, C. (4) 207 Raboisson, P. (4) 229; (6) 87 Rachon, J. (4) 98,295 Raczynsta, E.D. (7) 7 Rademacher, 0. (1) 198; (4) 320 Radkmky, A.E. (1) 224; (7) 14 Rager, M.-N. (7) 197 Raghu,K.V. (4) 12; (8) 43 Rai, A.K. (8) 64 Raible, A.M. (5) 98 Raimondi, M. (1) 258 Raithby, P.R (1) 113 Rajan, P. (4) 191 Raju, C.N. (4) 6,36,326; (8) 3 1, 122

Ritjur, S.B.(5) 208 Ramaiah, P. (6) 112 Ramaswamy, M. (I) 175 Ramesh, V.(5) 149 Rammo, J. (5) 215 Ramzaeva, N. (5) 155 Ranasinghc, M.G. (1) 205; (3) 24; (4) 241

Rankin,D.W.H. (1) 260 Rao, C.V.N. (4) 326; (8) 122

379

Rao, M.N.S. (1) 230 Rao, T.A. (8) 37 Rapko, B.M.(1) 306 Raptopoulou, C.P.(6)37 Rasadkina, E.N.(3) 36,38; (8) 111 Rastogi, RC. (3) 73; (5) 203 Raston, C.L. (1) 95 Rath, N.P. (4) 181 Ratmcycr, L. (5) 111 Rauk, A. (4) 328 Rautschek, H. (7) 157,160 Ravikumar, V.T.(5) 97 Ray, K.A. (3) 78 Raynaud, F. (5) 163 Rayner, B. (5) 130,131 R-0, J.S.(7) 60-62 Read, P.W. (1) 103 Reamer, RA. (1) 200 Reau, R (1) 53;293,538; (6) 9; (7) 165,167 Rebets, E.S.(1) 42 1 Rebiere, F. (1) 16 Reddy, B.S. (4) 5-12,37-39 Reddy, C.D. (4) 5-12,36-39,326; (8) 3 1,43, 122 Rcddy, D.B. (4) 36 Reddy, D.M.(5) 256 Reddy,D.R. (8) 3 I Reddy, G.S. (4) 326; (8) 122 Reddy, M.P. (5) 84 Reddy, M.S. (4) 11, 12,326; (8) 122 Reddy, P.M. (4) 5,6,8,36,37,39; (8) 31 Rddy, V.S.(3) 28,29 Reed, C.A. (1) 5 14; (3) 105 Reed, C.S. (7) 232,240 Reed, RW. (1) 293,514,535; (3) 105; (4) 3 12; (6) 14 Reedijk, J. (5) 217 Rees, C.W. (1) 199 Rees, N.H. (1) 266 Rcese, C.B. (5) 15 Regitz, M. (1) 166, 197,446,454, 480,484491,495,538,561; (8) 21,22,24 R e v , M. (5) 140 Reid, RG. (6) 102 Reilly, J.P. (5) 257 Reinhard, G. (1) 57 Reinhold, D.F. (4) 151 Reinhoudt, D.N. (4) I5 Rei~acher,H . 4 . (1) 5 15 Reisgys, M. (1) 78 Reising, J.G. (1) 5 16 Reiss, M. (1) 149 Reissig, H.-U. (6)'88

Rekesh, D. (5) 234 Rell, S.(1) 39, 100,468 Ren, X.F. (5) 196 Repetto, M. (8) 129 Reshetkova, RG.(8) 28 Rettig, S.J. (1) 161,240 Reye, C. (1) 262,263; (4) 3 10; (8) 109

Reynolds, M.A. (5) 189 Remik, V.S.(4) 3 11 Rhee, J.S.(8) 123 Rheingold, A.L. (1) 97,457,458;

(7)175 Rhie,D.Y. (4) 156 Rhihil, A. (4) 128 Riant, 0. (1) 16.26 Ricard, L. (I) 102, 126,463,542, 545,546,554,573;

(3) 96

Ricca, G. (4) 263 Richards, C.J. (1) 20 Richert, C. (5) 128 Richmond, M.G.(1) 250 Richtcr,R(l) 115 Re.&, H. (1) 63 Riede, J. (1) 101,394; (8) 46 Riegel, B. (1) 76,89,436,529 Riegcr, RA. (5) 237 Rielly-Gauvin, K. (4) 226 Riesel, L. (4) 58 Rihs, G. (3) 4; (4) 219 Riley, A.M. (4) 26 Riley, D.P. (7) 53 Rink, S.M. (5) 214 Rios, J.J. (7) 9 Robert, D. (4) 42,43 Roberts. B.E. (7) 252-254 Roberts, B.P. (4) 124 Robertson, H.E. (1) 260 Robins, M.J.(5) 5 1 Robinson,D. (1) 182 Robinson, G.H. (1) 98 Robles, 1.(3) 69; (5) 208 Rock, D. (7) 52 Rock, M.H. (4) 105; (6) 98 Rodios, N.A. (6) 37 Rodriguez, E. (1) 336 Rodriguez, G.M. (1) 111 Rodriguez, J. (6) 110 Rodriguez,O.P. (4) 240,301,302 Raer, T. (6) 44 Roepstorff, P. (5) 141 Roesler, H. (7) 157,160 Roeslcr, R (7) 20 1,202; (8) 93 Roger, W.L. (4) 226 Rogers, R.D.(1) 99 Roig, V. (5) 163 Roigk, A. (5) 2 15

OrganophosphorusChemistry

380 Roizard, D. (7) 226,286 Rojas-Rousseau, A. (4) 200 Rokita, S.E.(5) 226 Roller, P.P. (4) 35 Romanenko, E.A. (6) 39 Romanenko, V.D. (1) 435,456; (7) 36; (8) 5

Romanova, E.A. (5) 183 Rondon, A.C. (1) I Ronkova, E.V. (3) 38 Roos, B.O. (1) 565 Roqucs, B.P. (4) 2 1 1

Rosch, W. (1) 484 Rosche, F. (1) 576; (8) 40 Rosemqrcr, H. (5) 170 Rosenberg, I. (5) 49 Rosenblum, J.S. (4) 68 Rosenthal, U. (1) 25 1 Roskey, M.T. (5) 238,248,249 Ross, K.C. (5) 71 Rossi, J.C. (6) 117 Rossi, RA. (1) 8 1,82 Rossier, J. (5) 255 Rostovskaya, M.F.(4) 153 Rothschild, K.J. (3) 63; (5) 184 Roucoux, A. (1) 122; (3) 95,98 Roughton, A.L. (5) 54,128 Roumestant, M.L. (4) 203 Rouquette, H. (1) 320,321,326 Rousseau, G. (6) 36 Routledge, A. (5) 34,71,173 Roy, N.K. (8) 6 1 Royer, J. (3) 9; (4) 193 Royo, P. (1) 111 Rozanov, I.A. (7) 139 Rozenski, J. (5) 158 Rozhenko, A.B. (1) 470; (7) 5 Rozinov, V.G. (4) 286; (7) 169 Rozaas, E. (5) 21 Ruban, A. (7) 293; (8) 11 Rubin, Y. (5) 198 Rubinsztajn, S. (7) 57,61 Rudd, M.D.(8) 69 Rudler, H. (7) 197 Rudzevich, V.L. (1) 435 Rudzinski, J. (8) 125 Ruebenstahl, T. (7) 177,295 Rueddi, P. (4) 62 Ruehlicke, A. (1) 464 Ruel, R (4) 150 Ruc~imann,K.W. (7) 53 Ruhland, T. (6) 53 Ruhlandt-Sage, K.(8) % Rulkcns, R (1) 3 1; (7) 212 Runsink, J. (I) 14 Rupprich, T. (1) 294; (6) 8 Rusanov, E.B. (1) 247,435; (2) 10

Russell, C.A. (1) 113 Russo, G. (4) 2 10 Rutherford, T. (4) 30 Rutjes, F.P.J.T.(6) 132 Ruz& H. (1) 446 Ryan, K. (5) 80,89 Ryglowski, A. (4) 203 Ryono, D.E.(4) 226 Ryschkewitsch, G.E. (7) 3 Saady, M.(1) 206; (4) 250; (7) 12, 13,48 Saak,W.(1) 237 Saare,A. (1) 34 Saber, A. (4) 128 Saburi, M. (1) 261 Sadcghi, M.M. (5) 37 Sadowski, P.D.(5) 187 Saggs, S.R(7) 89 Sahasrabudhe, P.V. (5) 221 sahoo, S.P. (4) 99 Saiakhov, R (5) 39 Saito, T. (7) 272,290 Saito, Y. (1) 44 Sakai, H. (1) 12 Sakamoto, K. (5) 45 Sakamoto, M. (1) 414 Sakhibullina, V.G. (8) 10 Sakurai, H. (7) 150 Sakurai, M. (5) 12 SrJcurai, R (7) 290 Saleh, S.A. (6) 119 Salo, H. (3) 6 1,74; (5) 64 Salomon, C.J. (4) 254 Salzner, U.(1) 450; (8) 4 Samanta, S. (8) 61 Sambri, L. (6) 60 Samori, B. (5) 233 Sampath, U. (5) 195 Samstag,W. (3) 83 Samuel, 0.(1) 16 Sanchez,G. (7) 1 13 Sbchez, L. (6) 130 Sanchez,M.(1) 53,435,538; (6) 9; (7) 36 Sanders, T.C. (4) 299 Sandhu, P.K. (6) 126 Sandmeyer, F. (1) 506 Sandri, J. (6) 118 Saneyoshi, M. (5) 57 Sanghvi, Y.S.(5) 120 Sannes, K.A. (5) 254 Santi,D.V.(5) 82 Santiago, R (7) 172 Santiago-Garcia, R (6) 6; (7) 171 Santimaria, M. (I) 142

Saquet, M. (6) 94 Saraswathi, M. (1) 268 Sargeson, A.M. (5) 216 Sarikahya, F. (1) 360 Sarikahya, Y. (1) 360 Sarkcr, s. (5) 5 1 Sarkisian, M. (5) 270 Sarroca, C. (1) 364 Sarter, C. (6) 20 Smta, K. (3) 66; (4) 33,79 Sasai, H. (4) 129 Sasaki, M. (7) 155 Sasaki, T.(I) 370

Sasaki, Y.(7) 140 Sasaoka, M. (7) 277-279 Sasso, G. (1) 267 Sato, H. (7) 289 Sato, K. (8) 126 Sam, M. (6) 132 Sam, Y. (1) 418 Satoh, T. (5) 169 Sattlcr, E. (1) 72 Saunders, RS. (1) 507 Sauvageot, P. (1) 106 Savarino, P. (4) 263 Savignac, P. (4) 1 1 1, 163,253 Savin, A. (1) 436 Savkur, R (5) 209 Sawada,H. (1)411 Sawada, T. (4) 24 Sawai, H. (5) 174 Sawamura, M. (1) 127 Sawanishi, H. (4) 209 Sawasaki, K. (4) 55 Sawasaki, S. (4) 173 Say, P.B. (5) 189 Scalone, M. (1) 157 Swinge, S.A. (5) 83,86 Scettri, A. (6) 78 Schaefas, M. (1) 79 Schardt, S. (1) 440 Schnuer, S.J. (1) 92 Schaumann, E. (1) 333; (6) 65 Scheer, M.(1) 496 Schelcher, C.G. (4) 268 Scheler, U. (8) 50 Schcll, H. (1) 63 Schelle, C. (7) 192 Schemm, R (1) 516 Schepers, G.(5) 158 Schercr, J. (1) 59; (3) 92 Schick, G..(7) 78 Schickmann, H.(7) 58,157,158, 160 Schieffer, G.W. (8) 151 Schier,A. (1) 101,115,141,235; (7) 82;(8) 73

Author Index Schlewer, G. (4)28,29 Schleyer, P.von R (1) 89,260;(8) 8 Schliepe, J. (5) 166 Schlosser, M. (1) 4,5 Schmeusset,M. (1) 517 Schmid,R (1) 157 Schmidbaur, H.(1) 74,141,235, 394;(7)82;(8)46 Schmidpettr, A. (1) 292,423,449, 476-478;(3)44, 101;(6)10, 12,15,16;(8)25,26,73,110 Schmidt, A. (7) 26;(8)8 Schmidt, D.(1) 455 Schmidt, M. (1) 89,441; (8)25 Schmidt, U.(3)97;(4)199 Schmiedeskamp, B.K.(1) 5 16 Schmitt, H.W. (5) 114 schmiq L.(5) 1 1 Schmittel, M. (8)91 Schmock, F. (7)182 Schmutz, M. (3) 5; (4)218 Schmutzler, R (1) 241,274,278, 295,312,351,445;(2)22-24; (4)21,308,309;(8) 32,38,57 Schneider, B. (8)7 Schneidcr, H.J.(5) 215 Schneider, 0.(7)56,59,63 Schneider-KogIin, C. (1) 162 Schnetz, N. (4)29 schnick, w. (7) 10,ll Schoeller, W.W. (1) 223,259,451, 455,521,537;(6) 17;(7)25, 166;(8)1 SchoeUel, G. (1) 157 Schriver, M.J. (1) 492 SChr6de1, H.-P. (1) 449;(6) 12;(8) 25,110 Schrott, M. (1) 520;(6)48 Schudtt,J.M. (5)252 Schiitz, K.(3)76 Schuetz, M. (8)8 Schull,T.L.(1) 232 Schulte, G. (8) 163 Schultz, M.(7)26 Schultz, RG. (5) 110,123 Schulz, J. (4)30 Schumann, H.(I) 79 Schuster, J. (7)56 Schuster, K.(1) 496 Schuster, T.(4)279 Schutz, K.(5) 172 Schwab, J.J. (1) 134 Schwartz, D.A. (5) 189 Schwarz, W. (1) 75,88,89 Schweighofer,A. (1) 271;(8)146 Schweitzer, B.A.(5) 196

381 Schweizer, W.B. (3) 93 Schwing-Weil, M.-J. (1) 320,321 Scott, A.J. (6)113 Scott, G.K. (5) 36 Scott, J.S. (1) 186 Scott, S.R(7)135 Scremin, C.L.(5) 133, 134 Scudder, M. (1) 410 Seagall,Y. (2) 19 Seay,M.A. (7)65 Sebesta, D.P.(1) 210 Sebti, S.(4) 128 Seebach, D.(3) 93;(4)202 Seela, F. (5) 153,155,170 Segawa, K.(1) 19 Seiber, J.N.(8)132 Seidler, N. (1) 71 Seio, K.(5) 45, 169 Seitz, T. (1) 58 Seki, H.(1) 192 Seki, M. (4)196;(6)3 Sekine, M.(3) 59;(5) 45,121, 148,169 Sekya, T. (7) 154 Seligcr, H.(5) 72 Selkc, R. (1) 8,45, 139;(3) 91 Selvaratniun, S.(1) 266 Selqm, J. (8) 147 Semmva, M.G. (1) 284 Scn, D.(5) 227 Sendyurw, M.V. (1) 285,286 Senio, A. (1) 435 Sennhcnn, P.(1) 50,63 Scnthivel, P.(1) 230 Seo,K.(1) 310 Seoane, C.(6) 130 Scqucira, L.J. (1) 437;(3) 103 Sergeenko, G.G. (4)45 Sakov, I. (6) 1 17 Semau, V. (1) 86 Serra, M.V. (8) 18 Serves, S.V. (4)148 Scsenoglu, 0.(4)175 Seth, S.(6)46 svrcrth, D.(1) 417 Shabarova, Z.A. (5) 183 Shaffer, C. (5) 83 Shagidullin, RR (4)3 1 1 S h a i k h h v a , S.I. (1) 87,350 Shnkhni, D.B.(1) 420.42 I ;(6) 39 Shalcr, T.A. (5) 254 Shalev, D.E.(1) 224;(7)14 Shamsi, S.A. (8)103 Shamsuddm, M.(1) 135 Shang, L.(1) 175 Shang, Z.(8)66

Sharma, R.K.(8)64 Sharma, V. (7)148 S h e , S.(4)201 Sharpiov, K.T.(7) 19 Sharutin, V.V. (2)5,6 Shaw, B.L.(1) 13,135-137 Shaw, B.R (5) 59 Shaw, C.J. (8) 162 Shaw, RA. (7) 116-118 Shchedrova, N.M. (3) 48 Shchabakov, B.K.(1) 314 Shchcrbina, T.M. (4)49;(7)8 Shchetinin,A.M. (7)161 Shceka, H.M. (5) 1,2 Sheil, M.M. (5) 269 Sheik, C.J. (5) 196 Sheldrick, W.S.(1) 107,s16 Shen, H.F.(1) 250 Shen, H.X.(8)148 Shen,Y. (4)214,265 Shermolovich, Y.G. (1) 295 Shestakova, A.K. (1) 392 Shevchenko, I.V.(2)25;(3) 30 Shi, D.Q. (1) 388 Shi,J . 4 . (1) 47 Shibahara, A. (1) 44 Shibasaki, M.(4) 129 Shibata, I. (1) 369 Shibata, M. (1) 32 Shibuya, S.(4)135,141,276 Shields, T.P. (5) 212 Shilov, S.A. (1) 286 Shimasaki, C.(4)75 Shimazaki, N. (5) 8 Shimizu, 1. (1) 414 Shimayama, A.(5) 126 Shimura, K.(1) 536 Shin,J.I. (7)80 Shin, W.S. (4)269 Shinkai, I. (4)151 Shioiri, T. (1) 425;(6) 105,136 Shioji, K.(1) 270,349;(3) 107 Shiotsuka, M. (1) 574 Shirai. R (4)24;(6)114 Shirakata, N.(1) 2 14;(6)29 Shiratori, S.(1) 346 shishkin,O.V. (1) 353 Shishkov, LF.(4)328 Shivanyuk, A.N. (4) 16,19,20 Shklyarulc. B.(7)262 Shlyakhtcnko,L.S.(5) 234 Shoji, Y. ‘(7)272 Shokova, €.A. (4)91 S k e , J.M. (7) 119 Shriver, D.F.(7)241,242 Shtyrlin, Yu.G. (1) 169 Shudo, K.(5) 119

3 82 Shuey, S.W.(3) 56 Shulishov, E.V. (1) 166 Shumeiko, A.E. (7)109 Shuto, S.(5) 8 Shvetsov, Yu.S. (4)3 1 1 Siah, S.-Y. (1) 265,547 Sieler, J. (1) 110 Sierra, M.G.(8)50 Sierzchala, A. (4)317;(5) 100 Sigman, D.S. (5) 198 Sigmund, H.(3)70;(5)9 Sih, C.J. (5) 43,44 Sikmki, J.A. (4) 116 Sillanpaa, R (1) 238 Silveua, C.C.(6) 140 Silverio, S.J.(1) 506 Silverman, C.E.(8) 162 Silvwtru, A. (7)199 Silvestru, C. (7)68,201,202,294; (8) 93 Simmoneaux, G. (1) 195 Simon, N.(1) 320,321 Simonov, Y.A. (4) 14;(8) 112 Simpkins,N.S. (1) 337;(6)57 Sinden, R.R.(5) 21 1 Singer,M. (1) 340;(7)24 Singewald, E.T.(1) 85 Sinha, S.C.(6)134 Sinha-Bagchi,A. (6)134 Sinitsa, A.D.(2) 10 Sirirajan, V.(7)40 Siny, S.M.(7)83 Sitzmann, H.(1) 277 Siuzdak,G. (5)270 Siv, C.(4) 142 Sivakumnr, K.(4)319 Skloss, T.W.(7)221 Skordalakes, E.(4) 125 Skowrohska, A. (1) 138;(4)72, 73,305 skrzypczyriski,z.(4)54 Skvortsov,N.K. (1) 131;(4)306 Skwarczyhski, M. (4)252,296 Sladek, P.(7) 198 Slaney, M.(1) 140 Slang, M. (1) 488 Slawin, A.M.Z. (1) 375-378;(4) 3I4,321;(7) 193-195, 203-206;(8) 107 Slick, D.(7)159 Sliwa, H.(3) 34 Sliwakowski, M.(8) 144 Sloss, D.G. (4) 121;(6)84 Smeets, W.J.J(7) . 189 Smirnov, I.P. (5) 138,238,245, 248,249 Smith, A.B., 111 (4) 182,256;(6)

OrganophosphorusChemistry 121 Smith, B.D. (5) 6 Smith, C.L. (5) 246 Smith, D.E.(7)224,225,255 Smith, D.P. (5) 150,151 Smith, L.M. (5) 236 Smith, M.B. (1) 375,376;(7) 193-195 Smith, P.H. (1) 306 Smith, RD.(5) 272,273 Smith, RL. (1) 271,427;(8) 146 Smith, S.A. (4)226 Smolii, O.B.(1) 420,421;(6)39 Smolina, E.V. (1) 341 Smyth, M.S. (4)213 Snoeck, R (5) 30 Sobkowski,M. (5) 17,41 Soda,T. (2)21;(6)21 Sollhuber, M, (6) 125 Soh, K.-H. (4)23 Sohn, Y.S. (7)213,214,248 Sokolov, M.P. (4)294,303;(8) 41 Sokolowski,M.W. (8) 144 Solas, D.(4)212 Soleilhavoup, M.(1) 542 Solladie-Cavallo, A. (7)52 Solodar, A.J. (7)53 Solondcnko, V.A. (2)12 Solotnov, A.F. (1) 3 1 1 Soltek, R (1) 57 Solujic, L.(1) 55 1; (8)84 Somasundaram, N.(1) 194 Sommer, 0.(1) 462,465,557 Sommcr, T.J. (1) 340;(7)24 Sommese, A.G. (4)302 Song, H.(8) 124 Song, H.-L. (8)83 Sonveaux, E.(5) 200 Sopchk, A.E.(5) 222;(8) 77 Sopin, V.F. (4)303 Sotiropoulos, D.N.(4) 148 Sotiropoulos,J.-M. (1) 435 Soucek, M.D. (7)238 Soumies, F. (7)106, 108 Sowerby, D.B. (8)93 Spadari, S.(5) 58 Spek, A.L. (3) 31;(7)76,187-189 Spencer, I. (1) 29,164;(8)23 Spenm-BeaCh, G.G. (8) 159 Spiess, B. (4)28,29 Spilling, C.D. (4)181 Sprengeler, P.A. (4)256 Sprinz, J. (1) 63 Spunta, G.(3) 14;(4)133, 134 Srebny, H.-G. (7)58 S R ~ ~ W ~ I I I - MR ~ O(4) I I289 , Srinivasan, A.R (5)232

Srinivasan, C. (1) 194 Snvatsa, G.S.(5) 252 Sbchcl, H.-D. (7)42 Stalke, D. (1) 522,537;(3) 110; (6)17.48;(7)184, 185 Stamml~r,H.-G. (1) 438,462,464, 465,509,557 Stanforth, S.P. (1) 182 Staninets, V.I. (4) 117 Stanlcy, A.L. (1) 182 Stannek, J. (1) 502 Stannett, V.T. (7)236 Starkey, G.W. (1) 144 Stash,A.I. (3) 35;(4)235,306;(8) 108 Staltel, J. (5) 58 Stawinski, J. (3) 68;(5) 17,19,20, 40,41; (8)80 Stebani, J. (7)5 1 Stec. W.J. (4)60,317;(5) 48,92, 93,100,102 Steenvoorden, RJ.J.M. (5) 253 Stefaniak, L. (7)6 Skffen, J.-P. (8) 91 Stcigelmann, 0. (6)49 Steimann, M. (1) 15,109;(8) 105 Stein, RL.(4)99 Stcincr, A. (1) 1 13; (3) 110;(7) 131,184 Steiner, I. (1) 29 Steinhagen, H.(1) 63 Stcinmann, M.W. (3)5; (4)218 Stelzer, 0.(1) 153 Stcmmler, E.A. (5) 259 Stcnzel, V. (1) 287 Stcphan. D.W.(1) 112,246,523, 526,527 Stepnicka, P.(1) 160 Sterling,D. (6)55 Stem, C.L. (1) 85 Stewart,A.O. (6) 41 Stille, J.K. (1) 252 Stirling, D. (1) 359 Stobart, S.R (1) 117 Stockley, P.G. (5) 167 Stone,M.L. (7)284 Stork, G.(5) 123 Stossel, P.(1) 15 Streib, W.E. (1) 496 Streubel, R (1) 493,540 Strojek, S.(1) 400;(3)18 Stromberg, R (5) 19,21,35 Strub, D. (3)4.5; (4)218,219 Struchkov, Yu.T. (1) 177,338, 353;(3)37.40; (7) 19 Strutwolf, J. (8) 1 Studer, A. (4)202

Author Index Stults, J.T. (5) 98 Suades, J. (1) 54 Suarez, A.1. (8) 121 Subramanyam, C. (6) 24 Suemune, K. (4) 135 Sugawara, M. (1) 127 Sugiura, M. (3) 15; (7) 289 Suisse, I. (3) 98 Sulkowska, A. (7) 250,258 Sulkowski, W. (7) 250,258 Sullivan, D.R. (8) 19 Sumar, E.S.(7) 105 Sumpter, V. (5) 169 Sun,J.S. (5) 206,207

sun,x.(1) 495

Sung,Y.K. (7) 248 Suwinska, K. (8) 112 Suzuki, N. (1) 123 Suzuki,0. (8) 126 Suzuki, S. (7) 149 Suzuki,T. (1) 84; (5) 219; (7) 97 Svendsen, M.L.(5) 143 Swann, P.F. (5) 149 Swarug, K.C. (8) 53 S d l e r , D. (5) 83, 137 Swiss, K.A. (8) 9,72 Switzer, C. (5) 175,272 Syaribzhanova, RM. (3) 33 Sykara, G.D. (7) 117 Szabo, T. (5) 17 szantay, c. (1) 21 1,212 Szisllosy, A. (1) 128; (8) 60

383

Tamaoka, Y.(1) 214; (6) 29 Tamburini, M. (6) 60 Tambute, A. (8) 134 Tan, W.T. (5) 69 Tanaka, H. (7) 153 Tanaka, K. (1) 4 11; (4) 209,274; (5) 194; (6) 76,77,90

Tanaka, S. (6) 128 Tanaka, Y. (6) 27,32 Tanamachi, T. (1) 574 Tang, C.-C. (4) 82,83,227 Tang, J.X. (3) 81; (5) 132 Tang, J.Y. (3) 58,81; (5) 18,63, 66,132

Tang, K. (5) 246,264,267 Tang, X.D. (5) 265 Tani, K. (1) 44 Tnni, M. (7) 155 Tanigaki, T. (7) 125,140 Tanitsu, K. (7) 153 Tanizawa, I).(1) 369 Tanner, M.E. (4) 22 1 Tanner, P.A. (8) 97 Tanyeli, C. (4) 175 Tao,A. (2) 9 Tao, C. (1) 175 Tapscott, RE. (7) 89 Taranenko, N.1. (5) 243,268 Tashev, E. (1) 339 Tashiro, K. (I) 443 Tashlitsky, V.N. (5) 183 Tasz, M.K.(1) 356; (4) 240,300, 302,323,324

Taapken, T. (4) 262 Taber, D.F. (6) 119 Tabet, J.C. (5) 262 Tada, J. (7) 84,275,276 Taillandier, E.(5) 206 Taillefer, M. (4) 23 1; (6) 40; (7) 37

Takach, E.J. (5) 248,249 Takahashi, H. (1) 536 Takaku, H. (3) 57; (5) 68 Takamuku, S. (4) 55-57 Takashima, Y. (5) 125,126 Takatsuka, T. (6) 19 Takayama, M. (5) 244 Takayasu, T. (7) 46 Takefumi, T. (7) 84 Taketazu, K. (8) 39 Takiue, K.(7) 125 Talbo, G. (5) 250 Take, F.E.(7) 145,146,148 Tam, S.(5) 112 Tamagaki, S. (1) 380 Tamamura, H. (4) 35

Tatarinova, A.A. (1) 120 Tattershall, B.W.(8) 85 Taudien, S.(1) 16 Tawaraya, S.(1) 5 1 Taylor, C.M. (4) 182,256 Taylor, J . 4 . (3) 64; (5) 218 Taylor, N.J. (1) 530 Taylor, O.J. (1) 48 Taylor, P.N. (I) 154, 155 Taylor, RA. (5) 36 Taylor, R.J.(3) 89; (4) 13 1 Taylor-Meyers, S.(7) 22 1 Tebbe, K.F. (1) 397-399 Tebby, J.C.(1) 367; (4) 90,297; (8) 13,14,33

Tei, Y.(7) 278 Teixidor, F. (1) 238 Tejerina, B. (7) 183 Tenltuisen, K.S. (7) 240 Terfort, A. (1) 35 Terikovskaya,T.E. (1) 283 Terreno, E. (8) 16 Tenis, A. (6) 37 Teunissen, T.T. (1) 566,570,571

Thakut, S.K. (6) 139 Thelen, V. (1) 455 Thelin, M. (5) 17 Thsodorakis, E.A. (6) 132 Tlueffry, L. (3) 95 Thinus, B. (1) 7 1 Thissell,J.G. (4) 283 T ~ O C M C S H. S ~(1) ~ , 295; (8) 57 Tholey, A. (3) 87 Thomas, B.(7) 94 Thomas,1.P. (1) 64 Thomas,K.RJ. (7) 134,135 Thomas, M.A. (4) 283 Thompson, C.M. (8) 121 Thompson,D.P. (7) 61, 159 Thompson,N. (1) 320 Thomton-Pett, M.(1) 137 Thorp, H.H. (5) 213

Thrane, H. (5) 140 Thuong, N.T. (5) 163,191 Tian, F. (3) 7 Tiebes, J. (6) 132 Tillack, A. (1) 25 1 Tilley, J.W. (1) 2 17 Tillotson, M.R (1) 37 Timokhin, B.V.(4) 249 Timosheva, T.V. (2) 16 Tiripicchio, A. (1) 373,374,393 Tissot, 0. (8) 104 Tocke, L. (8) 1 16 Toda,F. (1)411 Toempe, P.(8) 116 Togashi, R (4) 33 Togni, A. (1) 29,163,164,267 Toke, L. (1) 128,575; (4) 239; (8) 60

Tokunaga, M. (4) 205 Tolbert, L.M. (6) 116 Toldov, S.V. (1) 131; (4) 306 Toledo, E.A. (I) 348 Tolmachev, A.A. (1) 247,282-284 Tolpekma, N.A. (7) 163 Tolppa, E.L. (8) 20 Tom&, M. (6) 6; (7) 171, 172 Tomita, T. (1) 370 Tomoskozi, I. (5) 109 Topaloglu, I. (1) 360 Tordo, P. (1) 264 Torres, M.C. (5) 237 Torwiehe, 8. (1) 509 Tobcano, RA. (7) 199; (8) 93 Tosquell~G.(5) 130,131 Toulme, J.J. (5) 159 Toupet, L.(1) 195 Toyota, K.(1) 32.29 1,43 1,432, 443,444,536

Tracz, D. (5) 83

3 84 Trauner, H.G.(1) 461,568 Treiber, D.K.(5) 79 Trinkhaus, S.(1) 45 Trishin, Yu.G. (4) 236,237 Troev, K.(4) 85 Trofmv, B.A. (1) 87, 119, 120, 350; (7) 122 Trost, B.M. (1) 234

Trostyanskaya, LG. (1) 290 Truffert, J.C. (5) 191 Tsai, H.-J. (6) 86 Tsarouhtsis, D.(5) 181 Tsay, S.C.(5) 37,50 Tso, P.O.P.(5) 154 Tmu, D. (5) 87 Tsuboi, S. (6) 79 Tsuchiya, K.(1) 416 Tsuchiya, T. (1) 346 Tsugawa, N. (6) 135 Tsujimoto, M. (1) 270; (3) 107 Tsukurimichi, E. (4) 75 Tsunoda, T. (1) 213,214,218; (6) 28-30

Tsuruoka, H. (3) 59; (5) 148 Tsuruta, H. (1) 188,190 Tsvetkov, E.N.( I ) 31 1,3 13,341 Tsymbal, I.F. (8) 112 T u b b i n g , U. ( 1) 259,45 I, 52 1; (8) 1

Tugui, M. (4) 119 Tuladkar, S.M.(2) 9 Tur, D.R(7)257,259 Turteltaub, K.W. (8) 153 T m w s k a , I. (3) 84,85; (5) 39 Tyagi, S. (4) 9,36 Tyka, R. (4) 179,223 Tyryshkin, N.I.(1) 169; (8) 10 Uchida, T. (1) 261 Uchida, Y. (1) 2 Uchiyama, K. (8) 136 Ueda, I. (6) 27 Uemura, M.(1) 12 Uemura, S.(1) 19,28 Ugi, I. (3) 42 Uhlmann, E. (5) 117,188 Ujszaszy,K. (1) 128,532; (4) 287; (8) 0

Umemiya, H. (5) 119 Umcno, M.(7)85 Umetani, S.(1) 370 Unmtcllcr, E. (6) 132 Uo, A. (I) 354 Uozumi, Y.(1) 25,123 Uragami, T. (7)287 Urbani, J.P. (6) 40

OrganophosphorusChemistty Usman, N. (5) 83,137,197,230 Ustynyuk, Yu.A. (I) 392 Utkin, P.Yu.( 1) 229; (7) 18 Vaganay, S.(4) 22 1 Vaghefi, M.M. (5) 106,189 Vaisscmann, J. (7) 197 Valdmama, M. (1) 371,372 Valerio, RM. (1) 204 Valcro, R (6) 33 Vak, J.-M. (1) 125 Valle, G. (1) 363,543; (6) 38 Vallcix, A. (7) 13 Valls, E. (1) 54 Vanacrschot, A. (5) 142,158 Van Baar, B.L.M. (1) 566 van Basten, A. (3) 17 van Boom, J.H; (3) 86,88 van de Grampel, J.C. (7) 123, 124 Vandenboom, D. (5) 246,267 van der Burgt, Y.E.M. (1) 6 van der Marel, G.A. (3) 86,88 van dcr Sluis, M.(1) 459 van Duynhoven, J.P.M. (4) 15 van Hcijenoort, J. (4) 22 1 van Hwnmel, G.J. (4) 15 Van Kea, A. (1) 453 van Leuwen, P.W.N.M. (1) 6,62; (3) 31

van Plew, D.(1) 61 Vanquickenbome, L.G. (1) 453 Van Riezen, H. (3) 5; (4) 2 18 Van Rooyen, P.H. (1) 429 Vanschepdael, A. (5) 235 Vansooliongen, I. (1) 17 Varbanov, S.(1) 339 Vasileva, T.V. (7) 163 Vass, A.A. (5) 266 Vasseur, J.J. (5) 120 Vassileva, V. (1) 339 Vassout, A. (3) 4,5; (4) 218,219 Vasyanina, L.K. (3) 32,33,47-49; (4) 322

vegh, P. (7) 9 Veith, M. (1) 433,5 13; (3) 106 Veits, Yu.A. (1) 55,178 Veldman, N. (7) 76,187,188 Velthuisen, E.J. (4) 172; (6) 96 Venanzi, L.M. (1) 1 16 Venkatesan, H. (5) 78 VepsllBinen, J. (4) 255 Verboom, W. (4) 15 vcrbruggcn, c. (4) 191 Vercaukren, I. (5) 159 Verentchikov, A.N. (5) 138 Verhorcvoort, K.L.(1) 1 13

Vcrkade, J.G. (2) 27,28; (3) 16; (8) 150

Verkruijsse, H.D.(1) 17 Veronese, F.M. (7) 243 Verri, A. (5) 58 Vcrics, A. (5) 265 Vestal, M.L.(5) 238 Viala, J. (6) 118 Viallcfont, P. (4) 203 Vicente, J. (1) 393 Vidal, C. (7) 106,108 Viehe, H.G. (6) 26 Vij, A. (7) 119 Vilaivan, T. (5) 261 Vilanucva, X.(6) I I0 Vilaplana, M.J. (6) 124; (7) 44 Vililkevich, A.G. (4) 238 Vilkov, L.V. (4) 328 Villacampa, M.D. (6) 70 Villani, C. (1) 347 Vinas, C. (1) 238 Vinayak, R (5) 87 V i m , R (5) 14 Vinogradova, T.K. (1) 389,390 Viottc, M. (1) 159 Visotsky, M.A. (4) 14 Visschcr, K . 8 . (7) 92,114,227, 239,247,296,297;

(8) 113

Viswanadham, G. (5) 124 Vlaar, C.P. (3) 23; (4) 232 Vogt, H.(8) 100 Vogt, W. (I) 32 1 Volkert, W.A. (7) 66 Volkov, E.M. (5) 183 Vollbmht, A. (2) 23,24; (4) 21 Voherhaus, R (7) 173 Volodin, A.A. (7) 163 von der Goenna,V. (8) 11 von Schnering, H.G. (1) 408,436 Von Sprecher, G. (3) 4,5; (4) 2 18, 219

Von Tungeln, L.S. (8) 152 Voherr, T. (4) 32 Vorob’ev, M.V. (4) 237 Vouros, P. (5) 235,271 Vovnova, V.I. (1) 456 Vrieze, K. (7) 187-189 Vyboischehiliov, S.F.(7) 69 Vydzhak, RN. (1) 389-391 Vysotskii, V.I. (4) 153,238 Vystotski, M.A. (8) 112

Wada, M. (1) 233,354 Wada, T. (3) 59; (5) 45,121,148, 169

wada,

Y.(1)

190,191

385

AufhorIndex Waddling, C. (7) 228 Wagencr, C.C.P. (1) 429 Wagner, M. (1) 52 Wagner, T.(1) 27 Wakamiya, T. (3)66;(4)33,79 Walcdt, S.M. (5) 31 Waldman, T.E.(7)53 Waldmeier, P.C. (3)4,5;(4)218, 219 Waldner, A. (5) 90 Walker, A. (1) 320 Walker, B. (3)6;(6) 103 Walker, B.J. (3)6;(6) 103 walker, I. (5) 34 Walker, RT. (5) 23 I Walker, S.(6)20 Walkowiak, U.(4)185 Wallace, K.(1) 429 Wallis, M.P.(5) 71 Walter, 0.(1) 57,58 Waltz, M. (8)27 Walz, M. (1) 77 Wang, B. (1) 525 Wang, C.(5) 224 Wang, D.G. (5) 122,154 Wang, G.(3)77;(5) 139 Wang, J. (4) 146;(8) 160 Wan& J.-L. (4)169 Wang, J.W. (5) 22 Wang, K.C. (1) 221 Wan& L. (1) 208 Wang, M.(1) 386;(4)63 W a g , Q. (4)78 Wan& Q.S. (8) 148 Wan& T.(7)230 Wan& W. (7)237 Wang, X.(1) 143 Ward, T.C. (7)266 Wardell, J.L. (1) 48 Warner, LM.(8) I60 Warren, S.(1) 309,327-332;(6) 5 I, 52,54,58,59,61-63 Waschbusch, K. (1) 567,569 Wasiak, J. (4)54 Wasserman, H.H. (6)42 Wasson, D.B. (5) 24 Wasylishen, RE. (1) 530,550, 551;(8)84 Watanabe, A. (7)291 Watanabe, K.A.(5) 13 Watanabe, M. (1) 46 Watanabe, N. (7)278 W a m b e , Y.(3) 108;(4)40 Watkins, C.L. (1) 92 Watson, P.G. (7) 101 Weber, B. (3)93 Weber, L. (1) 438,462,464-466,

481,509,557 Webcr, M. (3) 42 Wechter, W.J. (4)198 wedgwood, 0.(5) 5 Weetman, J.M. (3) 89;(4) 13 1 Wehmschulte, RJ. (1) 91 Weibel, J.M. (4)124 Weichmann, H. (1) 162 Weichscl, A. (1) 202,203 Weinkoetz, S.(1) 196 Wcis, U.(1) 517 Weiser, C.(5) 188 Weisman, A. (1) 60 Weiss, J. (I) 366 Wcissensteiner,W. (1) 22,23,43 Weith, H.L.(3) 77 Welker, M.F. (7)229 Wcllcr, F. (1) 324,576;(7)73, 176, 182,295;(8)29,40 Wellmar, U.(5) 61 Wclls, AS. (1) 187 Wells, RL. (1) 96,97 Wen, Y.H.(8)127 Wen, Y.S.(1) 358 Wendebom, S. (5) 90 Wmdt, H.-D. (7)58, 157,158, 160 Wengel, J. (5) 124, 140, 141, 143 Wenzel, T. (5) 170 Werner, H. (1) 70,179 Westbrook, J. (5) 232 Westerhausen, M.(1) 75 Wettling, T. (1) 197 Wheatley, M. (7)25 1,256 Whcatley, P.J. (2) 17 Wheeler,D.R (1) 507 While, M.L. (7)263 White,A.D. (I) 219 White, A.J.P. (1) 549 White,A.S.C. (1) 161 White, M.L. (7) 16,264,265 White,P.S.(1) 96,97 Whitehead, B.J. (4)266,267;(6) 4;(8) 34,35 Whitman, RH. (4)152 Whittle, RR (7) 132 Wick, K.(1) 165 Wickham, G. (5) 269 Wickham, J.N.(5) 254 Wickstrom, E. (5)38,190 Widhalm, M. (1) 22,23,66,150 Wiecmrek, M.W. (1) 307,355;(4) 183,305,317;(5) 93 Wiedlcin, J. (1) 94 Wiedmann, D.(1) 94 Wiemer, D.F. (5) 26 Wienk, M.M.(1) 361;(8)89,90 Wiesauer, C.(1) 43

Wicse, B. (1) 63 Wiesler, W.T. (3) 82;(5) 99 Wiethoff, J. (8) 105 Wijkmans, J.C.H.M. (3) 88 Wild, S.B. (1) 67,90,132,275, 276 Wilhelm, D. (4)291 Wilhelm, J.C. (4)74 Wilk, A. (5) 92,133,134 Wikie, J. (4)30,65,66 Will, D.W. (5) 117 Williams, C.A. (7)266 Williams, D.J. (1) 377,549;(4) 3 14;(7)200,203-205 Williams, D.M. (5) 56 Williams, D.R (6)41 Williams, H. (6)113 Williams, J.M.J. (4)261;(6)71 Williams, S.D.(1) 53 1 Williamson, J.R (5)79 Williard, P.G. (4)299 Willis, A.C. (1) 67,90,132,275, 276,531 Willis, C.L. (6)102 Willoughby. D.A.(7)249 Wills, M. (1) 189 Wilson, S.R (8)9.72 Wilson, W.D. (5) 1 1 1 Wilson, W.L. (1) 550 Wimmer, P. (1) 66,150 Wincotf F. (5) 83 Winkler, U.(1) 100,468 Winton, P.L. (6) 102 Wirsching, P. (5) I2 Wisian-Neilson, P. (7)216,230, 281 Wisnicwski, W. (1) 307 Wit, J.B.M. (1) 459 Witherington, J. (4)256 Witt, D.(4)98 Wocadlo, S. (7)70,71,176,178, 179 Wojtowicz, H. (4)191 Wolf, J.G. (7)36 Wolfsberger,W. (1) 70, 179 Wollins, J.D. (7) 193 Wolmershauser, G. (1) 277 Wolski, A. (1) 133 Wong, C.-H. (6)137 Wong, C.W. (2)29 Wong, C.Y. (2)4;(8)55 Won& W.(6)121 Wong-Mm, K.C. (1) 23 1 Wood, J.L. (6) 121 Wo~llins,J.D. (1) 375-379;(4) 314,321;(7)194,195,200, 203-206;(8)107

OrganophosphorusChemistty

3 86 Workman, C. (5) 83 Worl, R ( 5 ) 267 Womiak, L.( 5 ) 102 Wright, D.S. (1) 113; (7)131 Wright, G. (5) 58 Wright, L.C. (8) 19 WU,D.-X. (1) 47 Wu,G.P. (4) 82 Wu, H. (1) 304 Wu, H.L. (8) 127 Wu, K.J. (5) 254 Wu, Q.Y. ( 5 ) 273 WU, S.-Y. (4) 243 Wu,T.F. ( 5 ) 176 Wu,T.J. (1) 388 Wu, Y.S. (8) 152 Wclthrich, K.(3) 65; ( 5 ) 178 Wulff-Molder, D. (8) 100 Wyatt, P. (1) 309 Wycisk, R (7) 237 Wylie, P.L. (8) 136

Xi% C.-G. (8) 83 Xiang, G.B. ( 5 ) 161 Xiao, H.Y. (4) 95 Xiao, W.J. (1) 388 Xie, J. ( 5 ) 195 Xie, L. (1) 304 Xie, M.Q. ( 5 ) 5 I Xie, R (4) 224 Xe,Z.W. (1) 514; (3) 105 xil&z. (3) 53 XU,G.-F. (7)230 Xu,Q. (3) 20 Xu,Q.H. ( 5 ) 96 xu, w. (2) 9 Xu, Y.Z. ( 5 ) 149 Y a p , K.M.(4) 182,256 Yagi, M. (8) 141 Yamabe, T. (6) 128 Yamagishi, T. (4) 135,276 Yamago, S.(1) 41; (3) 11 Yamaguchi, K. (1) 188,190- 192 Yamagucht, T. ( 5 ) 57 Yamaguchi, Y.(1) 5 1 1 Yamamoto, A. (1) 414 Yamamoto, H. (I) 214,218; (6) 28,29 Yamamoto, I. (8) 39 Yamamoto, K.(2) 30 Yamamdo, T. (3) 108; (4) 40 Yamana, K.(5) 145,146 Yamane, S. (1) 24 Yamanoi, Y. (1) 192

Yamaoka, R ( 5 ) 219 Yamashita, K.(6) 123; (7) 41; (8) 62,63 Yamashita, M. (1) 3 10 Yamashita, Y. (6) 127 Yamataka, H. (6) 19 Yamazaki, M. (7) 272 Yan, Q.-J. (4) 78 Yan, S. (1) 33,362 Yan, Z.-X.(4) 169 Yanagawa, M. (1)41; (3) 11 Yang, F.L. (4) 71 Ymg, G.-F. (8) 44 Yang, G.S. (8) 148 Yang, H.(8) 66 Y M ~H.-Z. , (8) 44 Yang, J. (7)202 Yang, M. (7) 145,146,148 Yang, S.G. (4) 169 Yang, S.K.(7) 288 Yannopoulos, C.G. (5) 122 Yano, s. (7) 95-97 Yao, Q. (4) 5 1 Yao, S.J. (5) 11 I Yaouanc, J.J. (4) 77 Yap, G.P.A. (1) 97,457,458 Yarkevich, A.N. (1) 34 1 Yarkova, E.G. (8) 115 Yasui, S.(I) 269,270,349 Yasuke, S.(1) 346 Yasunami, M.(1) 291,431,432 Yasuoka, J. (3) 66; (4) 33,79 Yasvi, S. (3) 107 Yazbak, A. (6) 134 Yeh, J.Y. (1) 221 Yeola, S.N.(6) 119 Yieh, C.-H. (1) 56 Yin, P.(1) 38,65 Yokokawa, F. (6) 105 Yokomatsu, T. (4) 135,141,276 Yokoyama, s. (5) 45 Yoshifuji, M. (1) 32,291,431, 432,443,444,536 Yoshihara, M. (1) 349 Yoshikawa, A. (5) 146 Yoshimura, S.(7) 272 Yoshimura, T. (4) 75 Yoshioka, J. ( 5 ) 145 Yoshizaki, M.(7) 162 Yoshizawa, T. (1) 191 Young, K.M. (5) 106 Young, RN. (4) 150 Young, V.G. (1) 362 Yu, D. (3) 67; (5) 67,69,74,75, 108 Yy J. (3) 45; (8) 76 Yu, S.-H. (1) 124; (4) 25

Yuan, C. (4) 115,171,215,224, 225; (6) 99 Yuan, C.-Y. (8) 42 Yuceer, L. (1) 360 Yurchcnko, A.A. (1) 247,284,298 Yurchedco, RI. (1) 298; (4) 92 Zablocka, M. (1) 138,245; (7) 79 Zaccolo, M. ( 5 ) 56 Zadorin, A. (7) 262 Zah, Z. (7) 133 Zain, R (3) 68; (5) 17,19,20,40 zawlarov, L.S.(4) 49 Zambrano, J. (1) 234 Zanella, Y. (4) 163 Zanello, P. (1) 267 Zantour, H. (1) 335; (4) 245,248 Zapata, A.J. (1) 1 Zatorski, A. (5) 13 Zavalishina, A.I. (3) 47 Zawedzki, S.(1) 216; (4) 174 Zborovskii, Yu.L. (4) 117 Zemlyansky,N.N. (1) 392 Zcnneck, U. (1) 279 hnobi, R ( 5 ) 253 Zhm, D.J.(8) 152 Zhang, B. (6) 104 Zhang, C. (1) 173,3 16; (4) 107 Zhang, C.Z. ( 5 ) 123 Zhang, D. (8) 58 Zhang, F.J. (5) 43,44 Zhang, H. (3) 30 Zhang, J.C. (5) 52 Zhang, J.L.(3) 43 Zhirng, J.-X. (6) 131 Zhang, K. (4) 227 Zhang, L. (4) 146 Zhang, L.H.( 5 ) 22 Zhang,M. (8) 58 Zhmg R-Y. (1) 343; (6) 68 Zhang, S.(8) 5 1 zhan& w. (1) 18 Zhang, W.J.(5) 5 1 Zhang, X.(1) 61 Zhang, X.H. (5) 70

Zhang X.-M. (1) 409; (6) 2 B a n g , Y.-X. (8) 42 Zhang, Z. (3) 58.81 Zhang, Z.D. (5) 66,132 Zhm, B.P. (5) 187 Zhm, C.-G. (1) 343; (6) 68 Zhao, J. ( 5 ) 82 Zhao, K.(4) 146; (5) 22 Zhw, X.D. (5) 2 18 Zhao, Y. (1) 33,352 Zhm, Y.-F.(4) 34,78

Author Index

3 87

Zhao, 2.(6) 116 Zheng, P.(5) 226

Zhu, S.Z. (4) 307 Zhu, X.-F. (8) 65

Zhichkin, P.E. (7) 30 zhidkov, V.V.(2) 5

Zhu, Y.D.(5) 242 Zhu, Y.F.(5) 243,268 Zhuo, R (4) 3 15

zhong, Y.(8) 137, 138 ~ O U H.-J. ,

(4) 169 zhou, K.(1) 33 Zhou, L.(5) 133; (8) 137,138 Zhou, P. (5) 265 Zhu, C.(4) 132 Zhu, C.F. (4) 95

Ziller, J.W. (1) 234,507 Zillman, M.A. (5) 80 Zimmermann,

R (6) 44

Zinchenko, S.V. (4) 249 h g , H. (1) 386 & h a , E.F. (1) 350

Zou, R.M.(5) 129 Zsolnai, L. (1) 57,58 ZU, G.-F. (7)28 1 Zundel, G.(1) 344 Zutter, U.(1) 157 Zwicrzak, A. (1) 216; (4) 76, 174; (7) 38 Zyabilkova, T.A. (1) 563; (4) 294; (8) 28,4488 Zymariczuk-Duda,E.(4) 136,296 Zyuz, K.V.(1) 390