Fiesers' Reagents for Organic Synthesis (Volume 25)

Fiesers’ Reagents for Organic Synthesis VOLUME TWENTY FIVE Tse-Lok Ho Reagents for Organic Synthesis Fiesers’ Re...

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Fiesers’

Reagents for Organic Synthesis VOLUME TWENTY FIVE

Tse-Lok Ho

Reagents for Organic Synthesis

Fiesers’

Reagents for Organic Synthesis VOLUME TWENTY FIVE

Tse-Lok Ho

Copyright # 2010 by John Wiley & Sons, Inc. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/ go/permission. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and speciﬁcally disclaim any implied warranties of merchantability or ﬁtness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of proﬁt or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic format. For more information about Wiley products, visit our web site at www.wiley.com. ISBN 978-0-470-43375-1 ISSN 0271-616X

Printed in the United States of America 10 9

8 7

6 5

4 3 2

1

CONTENTS

General Abbreviations ix Reference Abbreviations xiii Reagents

1

Author Index 491 Subject Index 551

v

PREFACE In the Preface of ROS-24 I mentioned Ji Hsiao-Lan with the profoundest of admiration because of his role in editing the encyclopedic “Four Libraries of Books”. During preparation of the present volume I happened to be reading “The Meaning of Everything. The Story of the Oxford English Dictionary” by Simon Winchester. The heart-wrenching journey that lasted 71 years for the completion of the ﬁrst edition of the chef-d’oeuvre strikes a resonance in my heart. This volume covers chemical literature from the beginning of 2007 to the end of June, 2008. From this period the most glaring mosaic of chemical vision scintillates with an aura of aurum.

vii

GENERAL ABBREVIATIONS Ac acac ADDP AIBN An aq Ar ATPH 9-BBN BINOL Bn Boc bpy BSA Bt Bu Bz 18-c-6 cCAN Cap cat Cbz Chx cod cot Cp Cp CSA Cy cyclam DABCO DAST dba DBN DBU

acetyl acetylacetonate 1,10 -(azodicarbonyl)dipiperidine 2,20 -azobisisobutyronitrile p-anisyl aqueous aryl aluminum tris(2,6-diphenylphenoxide) 9-borabicyclo[3.3.1]nonane 1,10 -binaphthalene-2,20 -diol benzyl t-butoxycarbonyl 2,20 -bipyridyl N,O-bis(trimethylsilyl)acetamide benzotriazol-1-yl n-butyl benzoyl 18-crown-6 cyclo cerium(IV)ammonium nitrate caprolactamate catalytic benzyloxycarbonyl cyclohexyl 1,5-cyclooctadiene 1,3,5-cyclooctatriene cyclopentadienyl 1,2,3,4,5-pentamethylcyclopentadienyl l0-camphorsulfonic acid cyclohexyl 1,4,8,11-tetraazacyclotetradecane 1,4-diazobicyclo[2.2.2]octane (diethylamino)sulfur triﬂuoride dibenzylideneacetone 1,5-diazobicyclo[4.3.0]non-5-ene 1,8-diazobicyclo[5.4.0]undec-7-ene ix

x

General Abbreviations

DCC DDQ de DEAD DIAD Dibal-H DMA DMAD DMAP DMD DME DMF DMPU DMSO dpm dppb dppe dppf dppp dr DTTB E ee en er Et EVE Fc Fmoc Fu HMDS HMPA hv Hx i Ipc kbar L LAH LDA LHMDS

N,N0 -dicyclohexylcarbodiimide 2,3-dichloro-5,6-dicyano-1,4-benzoquinone diastereomer excess diethyl azodicarboxylate diisopropyl azodicarboxylate diisobutylaluminum hydride N,N-dimethylacetamide dimethyl acetylenedicarboxylate 4-dimethylaminopyridine dimethyldioxirane 1,2-dimethoxyethane N,N-dimethylformamide N,N0 -dimethylpropyleneurea dimethyl sulfoxide dipivaloylmethane 1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane 1,2-bis(diphenylphosphino)ferrocene l,3-bis(diphenylphosphino)propane diastereomer ratio 4,40 -di-t-butylbiphenyl COOMe enantiomer excess ethylenediamine enantiomer ratio ethyl ethyl vinyl ether ferrocenyl 9-ﬂuorenylmethoxycarbonyl furanyl hexamethyldisilazane hexamethylphosphoric amide light n-hexyl iso isopinocampheyl kilobar ligand lithium aluminum hydride lithium diisopropylamide lithium hexamethyldisilazide

General Abbreviations

LTMP LN lut M MAD MCPBA Me MEM Men Mes Mexyl MOM Ms MS MTO MVK nbd NBS NCS NIS NMO NMP Np Ns Nu Oc PCC PDC PEG Ph phen Pht Piv PMB PMHS PMP Pr py Qþ RAMP RaNi

lithium 2,2,6,6-tetramethylpiperidide lithium naphthalenide 2,6-lutidine metal methylaluminum bis(2,6-di-t-butyl-4-methylphenoxide) m-chloroperoxybenzoic acid methyl methoxyethoxymethyl menthyl mesityl 3,5-dimethylphenyl methoxymethyl methanesulfonyl (mesyl) molecular sieves methyltrioxorhodium methyl vinyl ketone norbornadiene N-bromosuccinimide N-chlorosuccinimide N-iodosuccinimide N-methylmorpholine N-oxide N-methylpyrrolidone naphthyl p-nitrobenzenesulfonyl nucleophile octyl pyridinium chlorochromate pyridinium dichromate poly(ethylene glycol) phenyl 1,10-phenenthroline phthaloyl pivaloyl p-methoxybenzyloxymethyl poly(methylhydrosiloxane) p-methoxyphenyl n-propyl pyridine quaternary onium ion (R)-1-amino-2-methoxymethylpyrrolidine Raney nickel

xi

xii

General Abbreviations

RCM Rf ROMP s(s) salen SAMP sc SDS sens. SEM SES TASF TBAF TBDPS TBDMS TBS TEMPO Tf THF THP Thx TIPS TMEDA TMS Tol TON Tp tpp Ts TSE TTN Z D ))))

ring closure metathesis perﬂuoroalkyl ring opening metathesis polymerization secondary solid N,N0 -ethylenebis(salicylideneiminato) (S)-1-amino-2-methoxymethylpyrrolidine supercritical sodium dodecyl sulfate sensitizer 2-(trimethylsilyl)ethoxymethyl 2-[(trimethylsilyl)ethyl]sulfonyl tris(dimethylamino)sulfur(trimethylsilyl)diﬂuoride tetrabutylammonium ﬂuoride t-butyldiphenylsilyl t-butyldimethylsilyl t-butyldimethylsilyl 2,2,6,6-tetramethylpiperidinooxy triﬂuoromethanesulfonyl tetrahydrofuran tetrahydropyranyl t-hexyl triisopropylsilyl N,N,N0 ,N0 -tetramethylethylenediamine trimethylsilyl p-tolyl turn over numbers tris(1-pyrazolyl)borato tetraphenylporphyrin tosyl ( p-toluenesulfonyl) 2-(trimethylsilyl)ethyl thallium trinitrate benzyloxycarbonyl heat microwave

REFERENCE ABBREVIATIONS ACIEE ACR BCSJ CB CC CEJ CL EJOC JACS JCCS(T ) JOC JOMC OBC OL OM S SC SL T TA TL

Angew. Chem. In. Ed. Engl. Acc. Chem. Res. Bull. Chem. Soc. Jpn. Chem. Ber. Chem. Commun. Chem. Eur. J. Chem. Lett. Eur. J. Org. Chem. J. Am. Chem. Soc. J. Chin. Chem. Soc. (Taipei) J. Org. Chem. J. Organomet. Chem. Org. Biomol. Chem. Organic Letters Organometallics Synthesis Synth. Commun. Synlett. Tetrahedron Tetrahedron: Asymmetry Tetrahedron Lett.

xiii

A Acetic anhydride. Dehydration.1 Ketoximes of alkyl aryl ketones afford pyrrolines on heating with Ac2O in dimethylacetamide. Cyclization probably proceeds via H-abstraction after the nitrenium ions are formed.

H NOH

Ac2O

N

AcNMe2 μw

68% 1

Savarin, C.G., Grise, C., Murry, J.A., Reamer, R.A., Hughes, D.L. OL 9, 981 (2007).

Acetylacetonato(1,5-cyclooctadiene)rhodium(I). Aryltrialkoxysilanes. Preparation of ArSi(OR)3 from ArX and HSi(OR)3 is readily accomplished with the aid of (acac)Rh(cod) in DMF.1 1

Murata, M., Yamasaki, H., Ueta, T., Nagata, M., Ishikura, M., Watanabe, S., Masuda, Y. T 63, 4087 (2007).

Acetylacetonato(dicarbonyl)rhodium(I). Alkynylation. Addition of 1-alkynes to a-keto esters is catalyzed by (acac)Rh(CO)2 in the presence of a hindered phosphine ligand [e.g., 2-(di-t-butylphosphino)biphenyl].1 Complexes containing more electron-rich analogues of the acetylaetonato ligand favor the reaction. Coupling. Allylic carbonylation and coupling with boronic acids transform 2,3-diazabicyclo[2.2.1]hept-5-enes into 5-hydrazinyl-2-cyclopentenyl ketones.2

X

N X N

+

RB(OH)2

(acac)Rh(CO)2

X

H N NX

R

CO TsOH, H2O

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 1

2

Acetyl chloride

Addition to a-dicarbonyl compounds.3 a-Diketones and a-keto esters react in aqueous DME with ArB(OH)2 to produce the monadducts. Reduction. Conjugated acids are converted to saturated aldehydes by syngas at room temperature, using (acac)Rh(CO)2 in conjunction with a special guanidine as catalyst.4 Only CO is liberated as stoichiometric side product. Furthermore, conditions for this highly selective reaction do not disturb acetals, esters, carbamates, ethers, silyl ethers, sulﬁdes and many other functional groups.

O

N L

H N H O

N

H N H O

H

Ph2P L

Rh H

R

Hydroformylation. With the Rh complex as catalyst (and a phosphite ligand) enamides and N-vinylimides are converted under syngas to a-amidoacetaldehydes.5 1

Dhondi, P.K., Carberry, P., Choi, L.B., Chisholm, J.D. JOC 72, 9590 (2007). Menard, F., Weise, C.F., Lautens, M. OL 9, 5365 (2007). 3 Ganci, G.R., Chisholm, J.D. TL 48, 8266 (2007). 4 Smejkal, T., Breit, B. ACIE 47, 3946 (2008). 5 Saidi, O., Ruan, J., Vinci, D., Wu, X., Xiao, J. TL 49, 3516 (2008). 2

Acetyl chloride. Nitration of arylamines. Nitration is performed by treatment of the [ArNHR2]NO2 salts with two equivalents of AcCl.1 Apparently, the active nitrating agent, AcONO2, is formed. 1

Zhang, P., Cedilote, M., Cleary, T.P., Pierce, M.E. TL 48, 8659 (2007).

N-Alkoxycarbonylazoles. Allyl carbonates. 1-Allyloxycarbonylimidazole is an allyloxycarbonylating agent for enolate ions (e.g., generated from ketones and NaHMDS in DME, 2788).1 O-Allylation occurs under the inﬂuence of BF3. OEt2. Substituted allyl groups are similarly transferred from homologous reagents. Carbamates, carbonates, and thiocarbonates are also readily prepared from the highly stable, nonhygroscopic, and usually crystalline mixed carbamates 1 of 3-nitro-1,2,4triazole.2

h3-Allyl(1,5-cyclooctadiene)palladium tetraﬂuoroborate

3

O RO

N

N NO2 N

(1) 1

Trost, B.M., Xu, J. JOC 72, 9372 (2007). Shimizu, M., Sodeoka, M. OL 9, 5231 (2007).

2

Alkylaluminum chlorides. Rearrangement. a-Siloxyarylacetaldehydes give aryl ketones on treatment with Me2AlCl. On the other hand, chloroaluminum biphenyl-2,20 -bis(triﬂylamide) catalyzes an alternative rearrangement pathway.1 O Me2AlCl

PhMe

R

Ar

OSiEt3

0o

Et3SiO Ar

CHO R TfN

Cl Al

NTf

O R

CH2Cl2

Ar OSiEt3

–20°

1

Ohmatsu, K., Tanaka, T., Ooi, T., Maruoka, K. ACIE 47, 5203 (2008).

S-Alkylisothiouronium salts. Thiol surrogates. These readily available compounds (RX þ thiourea) release RSH in the presence NaOH for conjugate addition. Essentially they are odorless thiolating agents.1 1

Zhao, Y., Ge, Z.-M., Cheng, T.-M., Li, R.-T. SL 1529 (2007).

h3-Allyl(1,5-cyclooctadiene)palladium tetraﬂuoroborate. Allylation.1 The Pd salt in the presence of 6-diphenylphosphino-2-pyridone catalyzes C-allylation of indoles (at C-3) and pyrroles (at C-2) with allyl alcohol in toluene at 508, generating water as the only byproduct. The key to activation of the allylating agent is by H-bonding.

4

h3-Allyl(cyclopentadienyl)palladium

Nucleophilic substitution.2 Benzylic acetates react with nucleophiles such as amines, sodium arenesulfonates, and malonic esters under the inﬂuence of the title reagent together with DPPF and a mild base [Et3N in EtOH or K2CO3 in t-AmOH]. 1

Usui, I., Schmidt, S., Keller, M., Breit, B. OL 10, 1207 (2008). Yokogi, M., Kuwano, R. TL 48, 6109 (2007).

2

h3-Allyl(cyclopentadienyl)palladium. Cycloaddition. The Pd complex is useful for generating internal salts containing a p-allylpalladium complex from (v-1)-methylene lactones. Trapping of the intermediates by other 1,3-dipoles such as nitrones results in the products of different types of heterocycles (with larger ring size).1

O O Ar

+

COOMe

HO N Ar" Ar'

O N Ar"

PdCp

O P N

MeOOC

O

Ar

Ar'

The subtle ligand effects are manifested in the reaction of dipolar species with acrylic esters, apparently due to different number of P-ligands on the p-allylpalladium complex. With two additional ligands (phosphites) on Pd the p-allyl segment suffers attack at the central carbon to eventually generate spiro[2.4]heptanes, whereas only one additional ligand (phosphine) engenders an electronic bias toward bond formation at the terminus.2 COOMe PdCp o -Tol3P

Ph O

COOMe O

Ph

COOMe

+

COOMe COOMe PdCp (i-PrO)3P

Ph

COOMe

Carboboration.3 An alkyl group is delivered from (alkyl)zirconocene chlorides to a triple bond accompanied by the formation of an oxaborolidine unit. Remarkably, Me3P (vs. other phosphine ligands) has a unique stereochemical inﬂuence.

Allylstannanes

iPr2N

iPr2N R

O

B

Cl

Cp2Zr(R")Cl

R"

R

PdCp

n

R'

n

O B

R

R"

PhMe, 110o

ligand:

iPr2N

O B

R'

5

R"' n

R'

R"'

Ar3P, Cy 3P, t-Bu3P

R"

Me3P (cis-addition)

(trans-addition)

Elimination.4 o-Quinodimethane is generated from (o-trimethylsilylmethyl)benzyl methyl carbonate on heating with the Pd complex and DPPE in DMSO at 1208. 1

Shintani, R., Murakami, M., Hayashi, T. JACS 129, 12356 (2007). Shintani, R., Park, S., Hayashi, T. JACS 129, 14866 (2007). 3 Daini, M., Yamamoto, A., Suginome, M. JACS 130, 2918 (2008). 4 Giudici, R.E., Hoveyda, A.H. JACS 129, 3824 (2007). 2

h3-Allyldichloro(triphenylphosphine)palladium. Borylsilylation.1 (Chlorodimethylsilyl)pinacolatoborane adds to 1-alkynes to give 1-pinacolatoboryl-2-silylalkenes. The relative amount of the addends is the determinant factor in the stereochemical outcome of the reaction

iPrO Si R PdCl2(PPh3) (excess alkyne)

R

B O

O

O +

Cl Si B

i PrO R Si

O PdCl2(PPh3) (excess silylborane)

O B O

1

Ohmura, T., Oshima, K., Suginome, M. CC 1416 (2008).

Allylstannanes. Allyl addition.1 Diastereoselectivity for the addition of an allyl group to hexacarbonyldicobalt complexes of 4-hydroxy-2-alkynals is much higher using allyltriphenylstannane instead of the tributyl congener.

6

Aluminum bromide

Co

Co

Co +

OHC

SnPh3

CH2Cl2 –40°

HO OR

Co

(i-PrO)2TiCl2

HO HO

OR

1

Hayashi, Y., Yamaguchi, H., Toyoshima, M., Okado, K., Toyo, T., Shoji, M. OL 10, 1405 (2008).

Aluminum bromide. Reductive phenylation.1 Naphthalenediols and benzene combine to afford hydroxytetralones. The transformation occurs when the mixtures of the aromatic compounds are treated with an excess of AlBr3. O

OH AlBr3

HO

PhH

HO Ph

1,5-; 1,6-; 1,7OH HO

O

AlBr3 PhH

HO Ph

2,6-; 2,71

Koltunov, K.Yu. TL 49, 3891 (2008).

Aluminum chloride. Friedel– Crafts acylation. A synthesis of chilenine is completed by a two-fold Friedel–Crafts acylation of an N-(arylethyl)amide with oxalyl chloride.1 O HN O

O

O

N OMe

AlCl3 (COCl)2

O

O OMe

O HO OMe

OMe chilenine

Acylation of arylidenecyclobutanes is accompanied by ring expansion.2 A route to norbornen-7-ones entails an intramolecular desilylative Friedel –Crafts acylation.3 Such compounds are not directly accessible by a Diels –Alder reaction.

Aluminum tris(2,6-diphenylphenoxide), ATPH

7

R AlCl3

Ar +

Me3Si

RCOCl

SiMe3 H O H

Ar

O

ClCH2CH2Cl

AlCl3 CH2Cl2

SiMe3 O COOH

O

O

75%

Carbimination. Thiophene and N-substituted pyrroles and indoles undergo electrophilic substitution with ArNC at room temperature. The reaction gives imines as products.4 Aromatization. Treatment of 6-hydroxy-1,2,3,6-tetrahydro-N-tosyl-3-pyridones with AlCl3 in MeNO2 at –788 brings about dehydration and O-tosylation to give 3-tosyloxypyridines.5 1

Kim, G., Jung, P., Tuan, L.A. TL 49, 2391 (2008). Jiang, M., Shi, M. OL 10, 2239 (2008). 3 Li, D., Liu, G., Hu, Q., Wang, C., Xi, Z. OL 9, 5433 (2007). 4 Tobisu, M., Yamaguchi, S., Chatani, N. OL 9, 3351 (2007). 5 Hodgson, R., Kennedy, A., Nelson, A., Perry, A. SL 1043 (2007). 2

Aluminum dimethylamide. Transamination.1 Tertiary amides are converted to secondary amides on reaction with secondary amines in the presence of Al2(NMe2)6. 1

Hoerter, J.M., Otte, K.M., Gellman, S.H., Cui, Q., Stahl, S.S. JACS 130, 647 (2008).

Aluminum iodide. Baylis –Hillman reaction. Ethyl propynoate apparently undergoes iodoalumination to generate a nucleophilic species that adds onto carbonyl compounds. (Z )-b-Iodoacrylic esters are produced.1 1

Lee, S.I., Hwang, G.-S., Ryu, D.H. SL 59 (2007).

Aluminum tris(2,6-diphenylphenoxide), ATPH. Macrolide synthesis.1 By way of an intramolecular aldol reaction using ATPH and LiTMP, macrocyclic (10-, 12-, and 14-membered) lactones are formed.

8

Aluminum triﬂate

O

OHC

HO

O

NLi

O n

O n ATPH

n = 1,3,5 1

Abramite, J.A., Sammakia, T. OL 9, 2103 (2007).

Aluminum triﬂate. Cycloisomerization.1 An oxime function is liable to add to a double bond at an appropriate distance and the reaction is realized by heating unsaturated oximes with Al(OTf)3 in MeNO2.

NOH

N

Al(OTf)3

Ph

O

Ph 84%

1

Cheminade, X., Chiba, S., Narasaka, K., Dunach, E. TL 49, 2384 (2008).

Aminocarbenes. Reviews.1,2 Applications of heterocyclic carbenes in organic synthesis have been reviewed. Aldol reactions. Enolization of ketones at room temperature (and ensuing silylation) is readily effected by 1,3-bis(1-adamantyl)imidazol-2-ylidene.3 Accordingly, Mukaiyama aldol reaction is accomplished under the appropriate conditions.4 Baylis–Hillman reaction products are obtained in an unconventional manner from a-silylpropargyl alcohols and aldehydes, using 1,3-bis(2,6-diisopropylphenyl)imidazol-2ylidene as catalyst.5 O

Ph HO

Si

+

R"CHO

OH

BuLi / THF;

R

R"

R R'

N

..

N

R'

Acyloin condensation. Carbene species (for promoting intramolecular acyloin condensation) are more readily generated from 1,2,4-triazolium salts when one of the N-substituents is highly electron-deﬁcient (e.g., 1).6 The bicyclic triazolium salt 2 derived

Aminocarbenes

9

from pyroglutamic acid catalyzes benzoin condensation in modest yields, in which electronrich ArCHO is less reactive but better asymmetric induction is observed.7 H O N N

N H

CF3

N N

N

Me3SiO Ph

Ph Cl

BF4 CF3

(1)

(2)

Analogous condensation of ArCHO and aldimines gives a-amino ketones.8 Carboxylic derivatives. A mixture of an aldehyde and a nitrosoarene is converted into an N-arylhydroxamic acid on treatment with 3 and DBU,9 whereas a,a-dichloro aldehydes gives a-chloro carboxamides in the presence of amines under similar conditions.10 A mild organic base is needed to generate the carbene (and a slight variation of the catalyst system for the same reaction comprises the N-mesitytriazolium chloride and imidazole base.11)

N

N N

BF4

F

X

F Ph

F

XH

RNH2

CHO

(3) N

F

CONHR

Ph OH N N N

F

(3) CHO

Ph

CONHR

Ph

There is a signiﬁcant difference in reaction proﬁle for the reaction of enals with nitrosoarenes. Isoxazolidin-5-ones are formed and alcoholysis of which leads to b-arylamino esters.12 With the nitroarenes replaced by arylazo carbonyl compounds to perform the reaction 3-oxopyrazoldinones result.13 As a redox process, the ring expansion of b-formyl-b-lactams to furnish succinimides14 and the ring scission of 2-nitrocyclopropanecarbaldehydes15 are also mediated by an azocarbene. R'

CHO

R

Mes N

R NR" O

R'

Cl N

DBU CH2Cl2

Mes

O

N R"

O

10

Antimony(V) chloride Cl

NO2

Bn N

NO2

S

i-Pr2NEt/R'OH

R

COOR'

R

CHO

>90% ee

Enals generated by oxidation of allylic alcohols with MnO2 in the presence of azolium ylides are trapped to form secondary allylic alcohols. These are subject to further oxidation and the resulting ketones undergo alcoholysis in situ.16 N

I N

R

OH

O

N

DBU MnO2

O

N

R N

N

R

OMe

1

Hahn, F.E., Jahnke, M.C. ACIE 47, 3122 (2008). Marion, N., Diez-Gonzalez, S., Nolan, S.P. ACIE 46, 2988 (2007). 3 Song, J.J., Tan, Z., Reeves, J.T., Fandrick, D.R., Yee, N.K., Senanayake, C.H. OL 10, 877 (2008). 4 Song, J.J., Tan, Z., Reeves, J.T., Yee, N.K., Senanayake, C.H. OL 9, 1013 (2007). 5 Reynolds, T.E., Stern, C.A., Scheidt, K.A. OL 9, 2581 (2007). 6 Takikawa, H., Suzuki, K. OL 9, 2713 (2007). 7 Enders, D., Han, J. TA 19, 1367 (2008). 8 Li, G.-Q., Dai, L.-X., You, S.-L. CC 852 (2007). 9 Wong, F.T., Patra, P.K., Seayad, J., Zhang, Y., Ying, J.Y. OL 10, 2333 (2008). 10 Vora, H.U., Rovis, T. JACS 129, 13796 (2007). 11 Bode, J.W., Sohn, S.S. JACS 129, 13798 (2007). 12 Seayad, J., Patra, P.K., Zhang, Y., Ying, J.Y. OL 10, 953 (2008). 13 Chan, A., Scheidt, K.A. JACS 130, 2740 (2008). 14 Li, G.-Q., Li, Y., Dai, L.-X., You, S.-L. OL 9, 3519 (2007). 15 Vesely, J., Zhao, G.-L., Bartoszewicz, A., Cordova, A. TL 49, 4209 (2008). 16 Maki, B.E., Chan, A., Phillips, E.M., Scheidt, K.A. OL 9, 371 (2007). 2

Antimony(V) chloride. Indanones.1 trans-2,3-Disubstituted indanones are produced in reasonably good yields from a mixture of arylalkynes and aldehydes with EtOH (1 equiv.) as additive, by treatment with SbCl5. O

R' R

1

+

SbF5

R"CHO

EtOH (1 equiv) ClCH2CH2Cl

Saito, A., Umakoshi, M., Yagyu, N., Hanzawa, Y. OL 10, 1783 (2008).

R'

R R"

Azobisisobutyronitrile

11

Arylboronic acids. Amide formation. o-Halophenylboronic acids catalyze the Diels– Alder reaction of acrylic acid as well as condensation of carboxylic acids with amines at room temperature (in the presence of 4A-molecular sieves).1 A thorough study indicates that (1-methyl-4-pyridinio)boronic acid iodide is a superior catalyst for amidation under azeotropic conditions, and esteriﬁcation of 2-hydroxyalkanoic acids.2 1

Al-Zoubi, R.M., Marion, O., Hall, D.G. ACIE 47, 2876 (2008). Maki, T., Ishihara, K., Yamamoto, H. T 63, 8645 (2007).

2

N-Arylsulﬁnylimines. Imido transfer.1 Aldehydes are converted into RCHvNAr on reaction with ArNvSvO, using catalysts such as VOCl3, MoOCl3, and MoO2Cl2. 1

Zhizhin, A.A., Zarubin, D.N., Ustynyuk, N.A. TL 49, 699 (2008).

Azobisisobutyronitrile. Deallylation. Allyl carboxylates are hydrolyzed under neutral conditions on treatment with AIBN (10 mol%) and water. This radical deallylation generally proceeds in high yields.1 Oxidative cyclization. Alkynyllactams cyclize by reaction with PhSH and AIBN, involving carbon radical shufﬂe.2

H AIBN, PhSH; MCPBA 180o

N O

1

N

OMe R

O

OMe R

Perchyonok, V.T., Ryan, S.J., Langford, S.J., Hearn, M.T., Tuck, K.L. SL 1233 (2008). Denes, F., Beauﬁs, F., Renaud, P. OL 9, 4375 (2007).

2

B Barium alkoxides. Aminoalkylation.1 The use of (ArO)2Ba in THF to deprotonate 3-butenoic esters for reaction with N-phosphinylaldimines gives a-substituted crotonates. O P Ph N Ph

O P Ph HN Ph COOBn R

COOBn +

(ArO)2Ba

R

Aldol 1 Michael reactions.2 A 2 : 1 condensation between ArCOMe and Ar0 CHO is observed when the mixtures are treated with (i-PrO)2Ba. O 2

Ar

+

Ar'CHO

O

(i-PrO)2Ba

Ar'

O

Ar

Ar

1

Yamaguchi, A., Aoyama, N., Matsunaga, S., Shibasaki, M. OL 9, 3387 (2007). Yanagisawa, A., Takahashi, H., Arai, T. T 63, 8581 (2007).

2

Barium hydride. Michael reaction.1 2-Cycloalkenones dimerize in the presence of BaH2. However, 2-cyclopentenone condenses with chalcone to form a bicyclo[2.2.1]heptanone. O BaH2

2

O O

Ar

O

O

Ar

BaH2

+

Ar' O

Ar'

O

1

Yanagisawa, A., Shinohara, A., Takahashi, H., Arai, T. SL 141 (2007).

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 13

14

Benzenesulfonic anhydride

Benzenesulfonic anhydride. Amide formation.1 Activation of carboxylic acids by (PhSO2)2O (with catalytic DMAP) as mixed anhydrides for acylation of R2NH is a very simple operation. 1

Funasaka, S., Kato, K., Mukaiyama, T. CL 36, 1456 (2007).

Benzyl N-phenyl-2,2,2-triﬂuoroacetimidate. O-Benzylation.1 Benzyl ethers of base-sensitive hydroxy esters and hindered alcohols are formed by reaction with the title reagent (Me3SiOTf as catalyst). The reagent is more stable than the trichloro analogue and it can be prepared from CF3C(vNPh)Cl and BnOH. 1

Okada, Y., Ohtsu, M., Bando, M., Yamada, H. CL 36, 992 (2007).

1,10 -Binaphthalene-2-amine-20 -phosphines. Substitution reactions. An SN2 reaction between 2-trimethylsiloxyfuran and acetylated Baylis–Hillman adducts is induced by the amine/phosphine 1.1

O

NHX PPh2

H R

O

(1)

R

(1) X = Ac, Ms

OSiMe3 +

R' O

O

O

R'

OAc

Actually the N-acetyl derivative catalyzes the aza-Baylis–Hillman reaction.2 1

Jiang, Y.-Q., Shi, Y.-L., Shi, M. JACS 130, 7202 (2008). Qi, M.-J., Ai, T., Shi, M., Li, G. T 64, 1181 (2008).

2

1,10 -Binaphthalene-2,20 -bis( p-toluene sulfoxide). Michael reaction. The title compound is a bidentate S,S-ligand for Rh. Complexes of the sort are used in mediating aryl transfer from ArB(OH)2 to 2-cycloalkenones and conjugated lactones under basic conditions.1 1

Mariz, R., Luan, X., Gatti, M., Linden, A., Dorta, R. JACS 130, 2172 (2008).

1,10 -Binaphthalene-2,20 -diamine derivatives. Aldol reaction. Asymmetric aldol reaction of chloroacetone with electron-deﬁcient ArCHO gives mainly the anti-3-chloro-4-hydroxy-2-butanones, in the presence of 1.1 The

1,10 -Binaphthalene-2,20 -diamine derivatives

15

protocol is valid for other ketones,2 and aldol reactions catalyzed by 2 have also been reported.3 O +

O

ArCHO

R

N H H H H NH N

Cl

NH

·PhCOOH

(1)

DMF, H2O

O

O

(1)

OH

R

Ar Cl

O NH

N H H

NH O

(2) Using bisthiourea derived from a chiral octahydro-BINAMINE as catalyst (with DABCO base) Baylis– Hillman reaction proceeds in 60– 88% ee.4 Conjugate addition. The parent chiral BINAMINE is an excellent ligand for CuCl2 to promote the conjugate addition of diorganozinc reagents.5 When complexed to carbene 3 palladium dicarboxylates exhibit catalytic activity in the aryl transfer from ArB(OH)2 to 2-cycloalkenones.6

N N

NMe

NMe

(3) Addition to multiple bonds. The semilabile acyloxy ligands in Pd complexes of 3 are exchangeable. In the reaction of allyltributylstannane with RCHO, p-allylpalladium species are formed via such an exchange.7

16

1,10 -Binaphthalene-2,20 -diamine derivatives

The aluminum complex 4 of the salen prepared from BINAMINE catalyzes a very interesting and useful reaction. It turns propargylsilanes into a-silylallylidenation agents for aldehydes such as glyoxamides.8

N Al O O N Cl

(4) Exquisite diastereochemical control is attained by tuning the relative bulk of the two alkoxy groups in ketene silyl acetals derived from a-alkoxyacetic esters, during aldol reaction with aldehydes. A chiral version is promoted SiCl4 in the presence of the phosphotriamide 5.9 The same set of reaction conditions is also applicable to create asymmetric quaternary carbon centers, for example, in the reaction of N-silyl ketenimines with ArCHO.10

N

O P

N

CH2

N 2

(5) OH OSiMe3 RO R"CHO

OR' +

SiCl4 i-Pr2NEt CH2Cl2

COOR'

R"

OR

(5) OH OSiMe3

RO

OR'

SiCl4 i-Pr2NEt CH2Cl2

R"

COOR' OR

R, R' small R, R' large

With complex 6 asymmetric addition of a-nitroalkanoic esters to imines is achieved.11

1,10 -Binaphthalene-2,20 -diamine derivatives

17

O N

Ni

N

O O

Ni O

(6) The rather unusual tetramidoytterbate anion 7 is responsible for asymmetric induction in an intramolecular hydroamination.12

R N

R –

N

Yb N

N RR

+

(thf)4Li

(7) Redox reactions. With PdI2 complexed to 3 kinetic resolution of secondary benzylic and allylic alcohols can be carried out via enantioselective oxidation (O2, Cs2CO3, PhMe, 808).13 The acetoxydiiodo-Rh carbene complex of 3 is a catalyst for asymmetric reduction of aroylacetic esters with Ph2SiH2.14 Substitution. Ullmann diaryl ether synthesis catalyzed by Cu(OTf)2 –BINAMINE occurs at a relatively low temperature (in dioxane, 1108, base: Cs2CO3).15 1

Guillena, G., del Carmen Hita, M., Najera, C. TA 18, 1272 (2007). Guillena, G., del Carmen Hita, M., Najera, C., Viozquez, S.F. TA 18, 2300 (2007). 3 Guizzetti, S., Benaglia, M., Raimondi, L., Celentano, G. OL 9, 1247 (2007). 4 Shi, M., Liu, X.-G. OL 10, 1043 (2008). 5 Hatano, M., Asai, T., Ishihara, K. TL 48, 8590 (2007). 6 Zhang, T., Shi, M. CEJ 14, 3759 (2008). 7 Zhang, T., Shi, M., Zhao, M. T 64, 2412 (2008). 8 Evans, D.A., Aye, Y. JACS 129, 9606 (2007). 9 Denmark, S.E., Chung, W.-j. ACIE 47, 1890 (2008). 10 Denmark, S.E., Wilson, T.W., Burk, M.T., Heemstra Jr, J.R. JACS 129, 14864 (2007). 11 Chen, Z., Morimoto, H., Matsunaga, S., Shibasaki, M. JACS 130, 2170 (2008). 12 Aillaud, I., Collin, J., Duhayon, C., Guillot, R., Lyubov, D., Schulz, E., Trifonov, A. CEJ 14, 2189 (2008). 13 Chen, T., Jiang, J.-J., Xu, Q., Shi, M. OL 9, 865 (2007). 2

18

1,10 -Binaphthalene-2,20 -dicarboxylic acids

14

Xu, Q., Gu, X., Liu, S., Dou, Q., Shi, M. JOC 72, 2240 (2007). Naidu, A.B., Raghanath, O.R., Prasad, D.J.C., Sekar, G. TL 49, 1057 (2008).

15

1,10 -Binaphthalene-2,20 -dicarboxylic acids. Addition to imines. Functionalized secondary amines are formed by addition of hydrazones1 and diazo compounds2 to aldimines, and these reactions are subject to asymmetric induction by 1.

COOH COOH

(1) 1

Hashimoto, T., Hirose, M., Maruoka, K. JACS 130, 7556 (2008). Hashimoto, T., Maruoka, K. JACS 129, 10054 (2007).

2

1,10 -Binaphthalene-2,20 -diol and analogues. Strecker synthesis. The 3,30 -disubstituted BINOL 1 is used in promoting addition of Me3SiCN to N-tosylketimines. Adding one equivalent of 1-adamantanol enhances reaction rates and enantioselectivity.1

O

H

N

O

N HH OH

O

OH H NH O

N H

(1)

1,10 -Binaphthalene-2,20 -diol (modiﬁed) – hafnium complexes

19

Addition reactions. Asymmetric allyl transfer from allyl boronates to N-acyl imines is assisted by (S )-3,30 -diphenyl-BINOL.2 Alkenyldimethoxyboranes react with conjugated carbonyl compounds with excellent enantioselectivity in the presence of a chiral 3,30 diiodo-BINOL.3 Allyl addition to hydrazones in the presence of 3,30 -bissulfonyl-BINOLs gives products in low to moderate ee (10 –68%), but much improvement(95–98% ee) is observed for using ﬂuorinated organosulfonyl analogues.4 For regioselective introduction of a chiral sidechain to C-2 of the indole nucleus the higher nucleophilicity of C-3 must be overcome. Employing the 4,7-dihydro derivatives the preferred reaction site is moved (to the active a-position of 4,5-disubstituted pyrroles), and asymmetric Michael reaction has been demonstrated with a chiral 3,30 -dibromoBINOL as catalyst.5 Br

R' N H

OH +

OH Br

R

(1)

R'

O N H

R

O

(1) Substitution reactions.6 3,30 -Bis(2-hydroxy-3-isopropylbenzyl)-BINOL causes opening of meso-epoxides by ArNH2 asymmetrically. 1

Hou, Z., Wang, J., Liu, X., Feng, X. CEJ 14, 4484 (2008). Lou, S., Moquist, P.N., Schaus, S.E. JACS 129, 15398 (2007). 3 Wu, T.R., Chong, J.M. JACS 129, 4908 (2007). 4 Kargbo, R., Takahashi, Y., Bhor, S., Cook, G.R., Lloyd-Jones, G.C., Shepperson, I.R. JACS 129, 3846 (2007). 5 Blay, G., Fernandez, I., Pedro, J.R., Vila, C. TL 48, 6731 (2007). 6 Arai, K., Salter, M.M., Yamashita, Y., Kobayashi, S. ACIE 46, 955 (2007). 2

1,10 -Binaphthalene-2,20 -diol – copper complexes. N-Arylation. Reaction of R2NH with ArI is completed at room temperature using the BINOL-CuBr complex as catalyst.1 1

Jiang, D., Fu, H., Jiang, Y., Zhao, Y. JOC 72, 672 (2007).

1,10 -Binaphthalene-2,20 -diol (modiﬁed) – hafnium complexes. Mannich reaction. A complex derived from (t-BuO)4Hf, imidazole and 6,60 dibromo-BINOL is air-stable. It is capable of asymmetric induction in catalyzing the Mannich reaction (80– 90% ee).1 1

Kobayashi, S., Yazaki, R., Seki, K., Ueno, M. T 63, 8425 (2007).

20

1,10 -Binaphthalene-2,20 -diol – iridium complexes

1,10 -Binaphthalene-2,20 -diol – iridium complexes. Allylation. A highly selective monoallylation of ketone enamines with allylic carbonates by the SN20 pathway is observed with a complex of BINOL of iridium(I).1 In the reaction ZnCl2 is also present. 1

Weix, D.J., Hartwig, J.F. JACS 129, 7720 (2007).

1,10 -Binaphthalene-2,20 -diol – magnesium complexes. Hetero-Diels– Alder reaction. The complex formed on treatment of BINOL with i-Bu2Mg shows excellent performance in catalyzing enantioselective cycloaddition of Danishefsky’s diene with aldehydes to give 2,3-dihydro-4H-pyran-4-ones.1 1

Du, H., Zhang, X., Wang, Z., Bao, H., You, T., Ding, K. EJOC 2248 (2008).

1,10 -Binaphthalene-2,20 -diol – niobium complexes. Aminolysis.1 The 3,30 -disubstituted BINOL 1 forms a complex with Nb(OMe)5 that has found use in catalyzing the opening of epoxides and aziridines with ArNH2.

OH OH OH OH

(1) 1

Arai, K., Lucarini, S., Salter, M.W., Ohta, K., Yamashita, Y., Kobayashi, S. JACS 129, 8103 (2007).

1,10 -Binaphthalene-2,20 -diol – titanium complexes. Addition to CvO. Asymmetric addition reactions involving tetraallylstannane,1 2-furyldiethylalane2 and (thf)AlAr33 to ketones in the presence of a titanium complex of BINOL has been studied. The unsymmetrical BINOL 1 and its octahydro derivative form Ti complexes that have been used in reactions with Grignard reagents4 and organozincs,5 respectively. Ph

Ph OH OH

(1)

1,10 -Binaphthalene-2,20 -diol – titanium complexes

21

A chiral catalyst system for aldol reaction of conjugated thioketene silyl acetals (i.e., from thio esters) consists of Ti-BINOL and (MeO)3B.6 The teranuclear Ti complex is air-stable and its use in aldol reactions requires low loading.7 A polymer with repeating 6,60 -dibutyl-BINOL units that are linked to each other at C-5 and C-50 has been synthesized. The Ti-complex of the polymer catalyzes the addition of alkynylzinc species to aldehydes.8 a-Cyanohydrin derivatives. BINOL 2, (1R,2S)-2-acetamino-1,2-diphenylethanol, and (i-PrO)4Ti self-assemble on admixture. The ensuing complex is a good catalyst for cyanoethoxycarbonylation of aldehydes.9 A simpler Ti catalyst is that obtained from 3-(1-imidazolyl)-BINOL 3, which serves in derivatization of ArCHO with Me3SiCN.10

N

Ph

N

N

OH

OH

OH

OH

N

Ph

(2)

(3)

Cycloaddition. Through empirical screening the dinuclear Ti complex 4 of 6,60 -diiodo-BINOL and the complex prepared from 5 have been chosen to promote 1,3dipolar cycloaddition (nitrone þ enal)11 and hetero-Diels –Alder reaction (Danishefsky’s diene þ RCHO),12 respectively. Ph I

I

O O Ti O O Ti O O O

Ph OH

I

OH OH

I

(4) 1

(5)

Wooten, A.J., Kim, J.G., Walsh, P.J. OL 9, 381 (2007). Wu, K.-H., Chuang, D.-W., Chen, C.-A., Gau, H.-M. CC 2343 (2008). 3 Chen, C.-A., Wu, K.-H., Gou, H.-M. ACIE 46, 5373 (2007). 4 Muramatsu, Y., Harada, T. ACIE 47, 1088 (2008). 5 Harada, T., Ukon, T. TA 18, 2499 (2007). 6 Heumann, L.V., Keck, G.E. OL 9, 4275 (2007). 7 Schetter, B., Ziemer, B., Schnakenburg, G., Mahrwald, R. JOC 73, 813 (2008). 8 Wu, L., Zheng, L., Zong, L., Xu, J., Cheng, Y. T 64, 2651 (2008). 2

22

1,10 -Binaphthalene-2,20 -diol – vanadium complexes

9

Gou, S., Liu, X., Zhou, X., Feng, X. T 63, 7935 (2007). Yang, F., Wei, S., Chen, C.-A., Xi, P., Yang, L., Lan, J., Gau, H.-M., You, J. CEJ 14, 2223 (2008). 11 Hashimoto, T., Omote, M., Kano, T., Maruoka, K. OL 9, 4805 (2007). 12 Yang, X.-B., Feng, J., Wang, N., Wang, L., Liu, J.-L., Yu, X.-Q. OL 10, 1299 (2008). 10

1,10 -Binaphthalene-2,20 -diol – vanadium complexes. Oxidative coupling. Vanadium complex 1A1 or 1B2 can be used in converting 2-naphthols to (R)-BINOLs and (S )-BINOLs, respectively, in air. R O

N O O

O2

V

O O O O V O N O R

OH

(1A)

OH

OH

(1A) R = sec-Bu (1B) octahydro, R = t-Bu 1

Guo, Q.-X., Wu, Z.-J., Luo, Z.-B., Liu, Q.-Z., Ye, J.-L., Luo, S.-W., Cun, L.-F., Gong, L.-Z. JACS 129, 13927 (2007). 2 Mikami, M., Yamataka, H., Jayaprakash, D., Sasai, H. T 64, 3361 (2008).

1,10 -Binaphthalene-2,20 -diol (modiﬁed) – zinc complexes. Addition to aldehydes. Organozinc addition to aldehydes with BINOLs as catalysts likely involves precoordination. 3,30 -Disubstituted BINOLs, especially with substituents providing additional ligating groups, are found to be highly effective, as exempliﬁed by the use of 1 and 2 in reaction of Et2Zn and alkynylzincs (in situ), respectively.1,2

N OH OH N

(1)

N

N OH

HO

OH

HO N

N

(2)

1,10 -Binaphthalene-2,20 -diol ethers

23

Alkynylzinc addition to ArCHO can also be carried out in the presence of 3,3 whereas the disilyl derivative 4 catalyzes enantioselective Reformatsky reaction on ketones (with ee up to 90%)4 which operates by a free radical mechanism (requiring air to initiate the reaction). Ph

Ph SiMe3

OMe OH

OH

OH

OH

OMe Ph

SiMe3

Ph

(3)

(4)

(S )-BINOL complexed to Et2Zn shows catalytic activity in the hetero-Diels– Alder reaction of Danishefsky’s diene and imine derived from ethyl glyoxylate.5 1

Milburn, R.M., Hussain, S.M.S., Prien, O., Ahmed, Z., Snieckus, V. OL 9, 4403 (2007). Li, Z.-B., Liu, T.-D., Pu, L. JOC 72, 4340 (2007). 3 Wang, Q., Chen, S.-Y., Yu, X.-Q., Pu, L. T 63, 4422 (2007). 4 Fernandez-Ibanez, M.A., Macia, B., Minnaard, A.J., Feringa, B.L. CC 2571 (2008). 5 Di Bari, L., Guillarme, S., Hanan, J., Henderson, A.P., Howard, J.A.K., Pescitelli, G., Probert, M.R., Salvadori, P., Whiting, A. EJOC 5771 (2007). 2

1,10 -Binaphthalene-2,20 -diol (modiﬁed) – zirconium complexes. Michael reaction. A complex derived from (t-BuO)4Zr and chiral 3,30 -dibromoBINOL induces the enantioselective conjugate addition of indole (at C-3) to enones.1 1

Blay, G., Fernandez, I., Pedro, J.R., Vila, C. OL 9, 2601 (2007).

1,10 -Binaphthalene-2,20 -diol ethers. Epimerization. The ether 1 forms imines with a-amino acids. Imines of L-amino acids suffer from A1,3-strain when maintaining a hydrogen-bonded conformation with the urea unit, therefore they are prone to undergo epimerization.1 H O OH

HN HN O

O

(1) 1

Park, H., Kim, K.M., Lee, A., Ham, S., Nam, W., Chin, J. JACS 129, 1518 (2007).

24

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites. Cycloaddition. The N-triﬂyl derivative 1 that has very bulky substituents at C-3 and C-30 is air-stable. It is an effective Bronsted acid for catalyzing 1,3-dipolar cycloaddition (of nitrones and vinyl ethers).1 An endo transition state is adopted for the reaction in which the proton simultaneously coordinates with oxygen atoms of both addends. In contrast, Lewis acids tend to favor the exo transition state.

O P O

O NHTf

(1) 1

Jiao, P., Nakashima, D., Yamamoto, H. ACIE 47, 2411 (2008).

Copper(I) complexes. Substitution reactions. Preparation of 2-branched 3-buten-1-yl bromides in the chiral form is conveniently accomplished by a Cu-catalyzed Grignard reaction in the presence of 2B or ent-2B.1 The valuable a-substituted allyl boronates are similarly accessed, although a report describes the use of the octahydro derivative of 2B.2

R O P N O R

(2A) R = Ph (2B) R = o-MeOC6H4 (2C) R = -Np

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites

25

Addition reactions. Chiral N-formylbenzylamines are formed by reaction of a Cu-catalyzed (ligand: 2A or ent-2A) organozinc reaction. It involves generation of N-formylaldimines from the a-sulfonylamine derivatives.3 Interestingly, the same system is applicable to imine trapping following conjugate addition to enones.4

O N

+

O S

O

R2Zn–Cu(OTf)2 (2A) Ph3P

HN

O S

H R' R

R' 1

Falciola, C.A., Alexakis, A. ACIE 46, 2619 (2007). Carosi, L., Hall, D.G. ACIE 46, 5913 (2007). 3 Pizzuti, M.G., Minnaard, A.J., Feringa, B.L. JOC 73, 940 (2008). 4 Gonzales-Gomez, J.C., Foubelo, F., Yus, M. TL 49, 2343 (2008). 2

Iridium complexes. Allylic substitution. The iridium complex of 2A is effective for catalyzing allylic substitution reactions, for example, in reaction of enamines with allylic carbonates to yield branched products.1 Chiral allylic ethers are similarly prepared.2 The reaction of allyl carbonates with arylzinc reagents also pursues an SN20 pathway preferentially, with Ir-complex of 1b as promoter, but asymmetric induction is only moderate.3 Using indole as nucleophile, substitution also proceeds.4 Primary allylic alcohols activated by (EtO)5Nb in situ are converted into branched allylic amines using iridium complex derived from [(cod)IrCl]2 and the (R,R,Sa) isomer of 2A.5 n O P N O Ph

(3) n = 12 The enantiomer of 2A catalyzes allylation of ammonia to provide branched diallylamines.6 If the nucleophile is changed to CF3CONHK or Boc2NLi a better ligand is 4. n O P N O OMe

(4) n = 12

26

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites

The double inversion mechanism that operates in the Ir-catalyzed decarboxylative decomposition of secondary allylic carbamates effectively converts allylic alcohols into the corresponding amine derivatives with complete retention of conﬁguration.7 Rearrangement. Transformation of 2-alkenols to 3-amino-1-alkenes can be performed via decarboxylative rearrangement of the derived carbamates, the iridium complex of 2B possesses activity for endowing chirality to the amines.8 When crotyl b-ketoalkanoate and homologues are exposed to the iridium complex of 2A in the presence of DBU, rearrangement and decarboxylation occur, forming optically active 1-alken-5-ones.9 1

Weix, D.J., Hartwig, J.F. JACS 129, 7720 (2007). Ueno, S., Hartwig, J.F. ACIE 47, 1928 (2008). 3 Alexakis, A., El Hajjaji, S., Polet, D., Rathgeb, X. OL 9, 3393 (2007). 4 Liu, W.-B., He, H., Dai, L.-X., You, S.-L. OL 10, 1815 (2008). 5 Yamashita, Y., Gopalarathnam, A., Hartwig, J.F. JACS 129, 7508 (2007). 6 Pouy, M.J., Leitner, A., Weix, D.J., Ueno, S., Hartwig, J.F. OL 9, 3949 (2007). 7 Singh, O.V., Han, H. OL 9, 4801 (2007). 8 Singh, O.V., Han, H. JACS 129, 774 (2007). 9 He, H., Zheng, X.-J., Li, Y., Dai, L.-X., You, S.-L. OL 9, 4339 (2007). 2

Nickel complexes. Hydrovinylation.1 Addition of ethylene to styrenes occurs in the presence of the Ni-complex of phosphoramidites. Tuning of the catalysts indicates the unsymmetrical aminophosphite 5 is a good performer for asymmetric induction.

Ph O P N O

(5) 1

Smith, C.R., RajanBabu, T.V. OL 10, 1657 (2008).

Palladium complexes. Hydrosilylation. Chiral a-arylethanol can be synthesized from styrenes via hydrotrichlorosilylation and oxidative desilylation. The ﬁrst step is accomplished with a Pd catalyst containing ligand 6.1

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites

27

Ph O

OMe P N

O

Cl

(6) Cycloaddition reactions. The aminophosphite H8-2C derived from octahydroBINOL is found to promote the [3þ3]cycloaddition of nitrones and trimethylenemethane derivatives to furnish 1,2-oxazines.2 Remarkable ligand effects have been observed in the spiroannulation of oxindoles: products possessing opposite conﬁguration at the spirocyclic center arise by changing the naphthyl substituents on the pyrrolidine ring (7A [a-Np] vs. 7B [b-Np]).3 CN (7A)

Ar O P N

O

O Ar

(7A) Ar = -Np (7B) Ar = -Np

N MeOOC

O N MeOOC

CN

(7B)

O N MeOOC

The bis-(b-naphthyl)pyrrolidinyl-containing ligand also ﬁnds use to induce chirality in the trimethylenemethane cycloaddition to imines, which leads to 2-substituted 4-methylenepyrrolidines.4 Another Pd-catalyzed reaction involves 1,2-di-t-butyldiaziridinone with dienes and it employs ligand 8.5

O P N O

(8)

28

1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites

Allylation. The multidentate ligand 9 has been developed for regioselective and diastereoselective allylation of ketones.6 O N NEt2

Fe

P O O

(9) 1

Li, X., Song, J., Xu, D., Kong, L. S 925 (2008). Shintani, R., Park, S., Duan, W.-L., Hayashi, T. ACIE 46, 5901 (2007). 3 Trost, B.M., Cramer, N., Silverman, S.M. JACS 129, 12396 (2007). 4 Trost, B.M., Silverman, S.M., Stambuli, J.P. JACS 129, 12398 (2007). 5 Du, H., Yuan, W., Zhao, B., Shi, Y. JACS 129, 11688 (2007). 6 Zheng, W.-H., Zheng, B.-H., Zheng, Y., Hou, X.-L. JACS 129, 7718 (2007). 2

Rhodium complexes. Hydrogenation. Phosphoramidite ligands to make up a Rh catalyst for enantioselective hydrogenation of dehydroamino acid derivatives include 10, which is derived from 3,30 -bis(diphenylphosphino)-BINOL,1 and 11 that contains two binaphthyl groups.2 PPh2 O

O P NR2

N

P

O

O

PPh2

(10)

(11)

Hydrogenation of alkenes by Rh catalysis is said to beneﬁt from multidentate sulfonamide-based ﬂexible phosphorus ligands such as 12 that are adaptive to hydrogen bondings.3

O P O

NH O S O

(12)

Bu

1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues

29

Hydroboration. Regioselective and enantioselective hydroboration of 3-alkenamides is accomplished with a Rh-catalyzed process. Formation of CZB bond at C-3 is due to amide group direction, and asymmetric induction originates from ligand 13.4 Ph

O P

N

O

(13) 1

Zhang, W., Zhang, X. JOC 72, 1020 (2007). Eberhardt, L., Armspach, D., Matt, D., Toupet, L., Oswald, B. EJOC 5395 (2007). 3 Patureau, F.W., Kuil, M., Sandee, A.J., Reek, J.N.H. ACIE 47, 3180 (2008). 4 Smith, S.M., Thacker, N.C., Takacs, J.M. JACS 130, 3734 (2008). 2

1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues. Hydrogen transfer. Using Hantzsch ester as hydrogen source imines undergo asymmetric reduction that is catalyzed by BINOL phosphates. The 3,30 -bis(9-anthracenyl)binaphthyl phosphate ent-1A mediates the saturation of CvN bond and semihydrogenation of a conjugated triple bond.1 Ar O

O P O

OH

Ar

(1A) (1B) (1C) (1D) (1E) (1F)

(1G) Ar = 4-PhC6H4 (1H) Ar = 3,5-(F3C)2C6H3 (1J) Ar = 4-(t-Bu)C6H4

Ar = 9-anthracenyl Ar = 9-phenanthryl Ar = -Naphthyl Ar = 2,4,6-triisopropylphenyl Ar = 4-ClC6H4 Ar = 4-O2NC6H4

Polyheteroaromatic systems containing a fused pyridine ring are susceptible to partial hydrogenation, with the pyridine ring the site of attack. The following examples involve 1A2 and 3,30 -bis(9-phenanthrenyl)-BINOL 1B.3 (1B)

N N R

R'

Hantzsch ester

NH R

N H

R'

30

1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues

Transfer hydrogenation of quinolines has also been studied using a 3,3-linked dimeric BINOL derivative 2 in which both subunits are phosphorylated.4

O O P O OH O O

(2) Due to intramolecular aldol reaction and the following Schiff base formation prior to transfer hydrogenation, cis-3-substituted cyclohexylamines are obtained from 1,5dicarbonyl compounds and ArNH2. The very crowded phosphate catalyst 1D is used in this transformation.5 Addition and cyclization reactions. Chiral propargylic amines are obtained from alkynylation of imines by catalysis of the silver salt of 1B.6 The enantiomer of phosphate 1D also ﬁnds use in the addition of indole to a-acetaminostyrenes.7 One more catalyst for intramolecular hydroamination to form pyrrolidine derivatives is the silylated 3.8 The reaction is conducted at 1308. SiPh3 O

O P

O

OH

SiPh3

(3) In the addition of indole to N-benzoyl aldimines, 3 also can be put to use.9 The catalyst 1F is for promoting reaction between ketene silyl acetals and N-(o-hydroxyphenyl)aldimines,10,11 and the 3,30 -dimesityl analogue for vinylogous Mannich reaction.12 The imines are suitably activated as shown below. Ar O

O

H O

P O Ar

O H

N R

1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues

31

It is not surprising that there are many other studies on analogous combinations that vary in catalyst (e.g., 1C,13 1D,14 and 1E15 ) and substrates. Formaldehyde hydrazones behave as nucleophiles in the reaction with aldimines. Chiral adducts are produced by conducting the reaction with octahydro-1B.16 The 3-component condensation for synthesis of 3-acyl-4-aryl-1,4-dihydropyridines from amines, b-dicarbonyl compounds and enals proceeds from enamine formation, Michael reaction and cyclodehydration is amenable to asymmetric induction, such as using ent-octahydro-1B.17 Three Mannich reactions occur in sequence when N-Boc aldimines and two equivalents of an N-vinylcarbamate are treated with 1G. 2,4-Diaminopiperidines are formed.18

N

Boc +

2 HN

Cbz

NCbz (1G)

Boc

N

CH2Cl2

R

R

NCbz

With 1B ligating to Rh2(OAc)4 to form a chiral catalyst for inducing insertion of methyl aryl(diazo)acetate into the O-H bond of a benzylic alcohol, it also enables further addition of the product into an aldimine. Both reactions are rendered asymmetric.19

Ar OH +

N2

MeOOC

Ar Ar'

O Rh2(OAc)4

Ar'

MeOOC

(1B)

Ar'

Ar'

NHAr"

NHAr"

Pictet –Spengler reaction for preparation of tetrahydro-b-carbolines is rendered enantioselective by one of the BINOL-phosphate, as previously reported. A modiﬁed version describes the effectiveness of 1H with tryptamine protected in the form of a triphenylmethanesulfenamide.20 Nazarov cyclization is successfully conducted with the phosphoryl triﬂimide derivative of 1B.21 Michael reaction to combine indole and b-nitrostyrene occurs on catalysis of 3 at –358.22 Condensation reactions. In highly diastereoselective and enantioselective manner anti-adducts are formed when enecarbamates are brought together with ethyl glyoxylate in the presence of 1J, which activates the formyl group by H-bonding. The adducts furnish chiral ethyl 2-hydroxy-4-oxoalkanoates on workup.23

32

1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues

O EtOOC

(1J), CH2Cl2;

H

H3O+

NHCOOMe +

RCH

OH O R'

EtOOC R

R'

ee >99%

Enantioselective aza-Henry reaction can be conducted with H8-3.24 Miscellaneous reactions. BINOL-phosphate 1D has also found applications in a Pd-catalyzed allylation of aldehydes by 1-benzhydrylamino-2-alkenes,25 and epoxidation of enals with t-BuOOH.26 Azomethine ylides are strongly H-bonded to 4, therefore 1,3-dipolar cycloaddition is dominated by its chirality.27

O O P O

O

O HO P OH O

O

(4) 1

Kang, Q., Zhao, Z.-A., You, S.-L. OL 10, 2031 (2008). Rueping, M., Antonchick, A.P. ACIE 46, 4562 (2007). 3 Metallinos, C., Barrett, F.B., Xu, S. SL 720 (2008). 4 Guo, Q.-S., Du, D.-M., Xu, J. ACIE 47, 759 (2008). 5 Zhou, J., List, B. JACS 129, 7498 (2007). 6 Rueping, M., Antonchick, A.P., Brinkmann, C. ACIE 46, 6903 (2007). 7 Jia, Y.-X., Zhong, J., Zhu, S.-F., Zhang, C.-M., Zhou, Q.-L. ACIE 46, 5565 (2007). 8 Ackermann, L., Althammer, A. SL 995 (2008). 9 Rowland, G.B., Rowland, E.B., Liang, Y., Perman, J.A., Antilla, J.C. OL 9, 2609 (2007). 10 Itoh, J., Fuchibe, K., Akiyama, T. S 1319 (2008). 11 Yamanaka, M., Itoh, J., Fuchibe, K., Akiyama, T. JACS 129, 6756 (2007). 12 Sickert, M., Schneider, C. ACIE 47, 3631 (2008). 13 Kang, Q., Zhao, Z.-A., You, S.-L. JACS 129, 1484 (2007). 14 Terada, M., Sorimachi, K. JACS 129, 292 (2007). 15 Guo, Q.-X., Liu, H., Guo, C., Luo, S.-W., Gu, Y., Gong, L.-Z. JACS 129, 3790 (2007). 16 Rueping, M., Sugiono, E., Theissmann, T., Kuenkel, A., Ko¨ckritz, A., Pews-Davtyan, A., Nemati, N., Beller, M. OL 9, 1065 (2007). 17 Jiang, J., Yu, J., Sun, X.-X., Rao, Q.-Q., Gong, L.-Z. ACIE 47, 2458 (2008). 18 Terada, M., Machioka, K., Sorimachi, K. JACS 129, 10336 (2007). 19 Hu, W., Xu, X., Zhou, J., Liu, W.-J., Huang, H., Hu, J., Yang, L., Gong, L.-Z. JACS 130, 7782 (2008). 20 Wanner, M.J., van der Haas, R.N.S., de Cuba, K.R., van Marseveen, J.H. ACIE 46, 7485 (2007). 21 Rueping, M., Ieawsuwan, W., Antonchick, A.P., Nachtsheim, B.J. ACIE 46, 2097 (2007). 22 Itoh, J., Fuchibe, K., Akiyama, T. ACIE 47, 4016 (2008). 23 Terada, M., Soga, K., Momiyama, N. ACIE 47, 4122 (2008). 2

1,10 -Binaphthalene-2,20 -diyl phosphites

33

24

Rueping, M., Antonchick, A.P. OL 10, 1731 (2008). Mukherjee, S., List, B. JACS 129, 11336 (2007). 26 Wang, X., List, B. ACIE 47, 1119 (2008). 27 Chen, X.-H., Zhang, W.-Q., Gong, L.-Z. JACS 130, 5652 (2008). 25

1,10 -Binaphthalene-2,20 -diyl phosphites. Hydrogenation. For an effective asymmetric hydrogenation of itaconic esters, the heterocomplex with Rh(I) center associated with two BINOL-derived phosphites of opposite electron-richness (1A, 1B) emerges as a more active and selective catalyst.1 Also having been examined are 22 and the one bearing a carboranyl residue.3

O

O

Ar

P O

P O

N

O

O

Fe

(2)

(1A) Ar = 3,5-(MeO)2C6H3 (1B) Ar = C6F5

With Rh(I) salts heterobidentate ligands such as 3 form catalysts of greater activities than homobidentate ligands 4, for enantioselective hydrogenation of acrylate and cinnamate esters. The ﬁndings are rationalized in terms of conformational and allosteric effects of the substrates.4

O O

PPh2

O P

P O

(3)

P O

O

(4)

In using the complex [Ir(cod)Cl]2 to conduct hydrogenation of imines, optimal diastereoselectivity is observed with mixed chiral/achiral ligands, as exempliﬁed by BINOL phosphite and Ph3P.5 Aminohydroxylation. Enolate anions generated from enol silyl ethers (by CsF) undergo Ag-catalyzed a-aminohydroxylation with PhNvO. An enantioselective version is readily performed in the presence of the phosphite ligand 5.6

34

1,10 -Binaphthalene-2-diarylphosphines

Ph O P OPh O Ph

(5) 1

Lynikaite, B., Cvengros, J., Piarulli, U., Gennari, C. TL 49, 755 (2008). Gavrilov, K.N., Maksimova, M.G., Zheglov, S.V., Bondarev, O.G., Benetsky, E.B., Lyubimov, S.E., Petrovskii, P.V., Kabro, A.A., Hey-Hawkins, E., Moiseev, S.K., Kolinin, V.N., Davankov, V.A. EJOC 4940 (2007). 3 Lyubimov, S.E., Tyutyunov, A.A., Kalinin, V.N., Said-Galiev, E.-E., Khokhlov, A.R., Petrovskii, P.V., Davankov, V.A. TL 48, 8217 (2007). 4 Norman, D.W., Carraz, C.A., Hyett, D.J., Pringle, P.G., Sweeney, J.B., Orpen, A.G., Phetmung, H., Wingad, R.L. JACS 130, 6840 (2008). 5 Reetz, M.T., Bondarev, O. ACIE 46, 4523 (2007). 6 Kawasaki, M., Li, P., Yamamoto, H. ACIE 47, 3795 (2008). 2

1,10 -Binaphthalene-2-diarylphosphines. Silylboration. Methylenecyclopropanes undergo functionalization on breaking the ring at an sp 2Zsp 3 bond in a Pd-catalyzed reaction with silylboronates. The products are alkenylboronates.1 R

O +

P

R'3Si B O

R (dba)3Pd2

R

(1) R

(1)

SiR'3 O B O

1

Ohmura, T., Taniguchi, H., Kondo, Y., Suginome, M. JACS 129, 3518 (2007).

Bis(acetonitrile)dichloropalladium(II). Coupling reactions. Sequential and chemoselective coupling reactions have been developed for 3-chloro-4-arylthio-1,2-cyclobutenones. Thus a Stille coupling replaces the chlorine atom with a Suzuki coupling to follow. Two different Pd complexes are used.1

Bis(acetonitrile)dichloropalladium(II)

35

ArSnBu3, (MeCN)2PdCl2 MeO

Cl

O

S

O

ArB(OH)2, (dba)3Pd2 CuTC, Fu3P

The Pd complex is useful for B-arylation of 4,4,6-trimethyl-1,3,2-dioxaborinane with ArI.2 Preparation of the very active catalyst (X-Phos)2Pd from (MeCN)2PdCl2 starts by ligand exchange with TMEDA, which is followed by reaction with MeLi at 08, and further treatment with X-Phos and 2-(o-chlorophenyl)ethylamine, prior to warming to room temperature to split off indoline.3 The precatalyst (before elimination of indoline) can be used directly for N-arylation of arylamines. TMEDA;

(MeCN)2PdCl2

MeLi

(tmeda)PdMe2

Cl

[(X-Phos)Pd]

NH2

Cy2P

25°

Pd Cl

NH2 X-Phos

Heterocycle synthesis. Highly substituted furans are obtained from 2-alkylidene-3alkynones via conjugate addition to generate enols that show nucleophilicity at C-3.4 R4

R5 R6

R2

+

X

4 R2 R (MeCN)2PdCl2 K2CO3/MeCN [NuH]

R3

[Nu] R1

R6 R5

O

R3

R1

Wacker oxidation of N-acylpropargylamines through neighboring group participation gives 5-formyloxazoles.5

36

Bis(acetonitrile)dichloropalladium(II)

CHO (MeCN)2PdCl2

O R

CuCl2/O2 DMF, 100°

N H

O R

N

Dihydropyran formation by a 6-endo-dig cyclization from 4-alkynols is achieved with (MeCN)2PdCl2 as catalyst, Pd(OAc)2 is much inferior for structurally complex substrates as that shown below.6

RO

RO (MeCN)2PdCl2

OH

Me3Si

OTBS

O

Ar3P/THF

COOMe

Me3Si

OTBS

COOMe

R = PMB 60%

Heterocycle formation proceeds from exposure of phenols, aroic acids and amides that contain an o-cyclopropyl substituent to (MeCN)2PdCl2 [and benzoquinone as reoxidant of the catalyst].7

(MeCN)2PdCl2

OH

BQ dioxane 80°

O

(MeCN)2PdCl2

COXH

O

BQ dioxane 80°

O

NR O

X = O, NR for X = O

1

for X = NR

Aguilar-Aguilar, A., Pena-Cabrera, L. OL 9, 4163 (2007). Murata, M., Oda, T., Watanabe, S., Masuda, Y. S 351 (2007). 3 Biscoe, M.R., Fors, B.P., Buchwald, S.L. JACS 130, 6686 (2008). 4 Xiao, Y., Zhang, J. ACIE 47, 1903 (2008). 5 Beccalli, E.M., Borsini, E., Broggini, G., Palmisano, G., Sottocornola, S. JOC 73, 4746 (2008). 6 Trost, B.M., Ashfeld, B.L. OL 10, 1893 (2008). 7 He, Z., Yudin, A.K. OL 8, 5829 (2006). 2

Bis(h3-allyl)dichlorodipalladium

37

Bis(h3-allyl)dichlorodipalladium. Addition. Group transfer from boronic acids to aldehydes can be carried out with the Pd complex in the presence of carbene 1.1

N

..

N

N

..

N

S

S Ph

(1A)

(1B)

Substitution reactions. Benzylation of phenols by benzyl methyl carbonates with Pd catalysis proceeds via transesteriﬁcation and decarbonylation.2 Triarylmethanes are obtained from a reaction of benzhydryl carbonates with arylboronic acids.3 1,3-Transpositional reduction, as pioneered by Tsuji, is a general method for synthesis of 3-methylenated azacycles.4 Hydrosilanes can be used in reductive deﬂuorination.5

AcO

n

N TS

PdCl

n

2

Ar3P HCOOH, Et3N

N TS

n = 0, 1, 2

F R

F

PdCl

R'

F 2

PhSiH3, Et3N DPPP/EtOH

R

R'

A convenient preparation of 3-amino-1-alkenes involves allylic substitution of primary carbonates with BnONH2, Ph3CCONH2, or Ph2CvNNH2, followed by treatment of the products with Zn-HOAc.6 Related work indicates the critical requirement of a base (DBU) to ensure the generation of branched isomers (conditions: [(h3-C3H5)PdCl]2, (EtO)3P, THF).7 Chiral 2-vinyl-1,2,3,4-tetrahydroquinolines are accessible by a Pd-catalyzed (SN20 ) cyclization in the presence of 1.8 A remarkable change of enantioselectivity in the Pd-catalyzed allylic substitution with amines by changing the o-substituent (CH2OR to COOMe) to the diphenylphosphino group of the ferrocenyldiphosphine ligand 2.9 a-Arylation of aldehydes is performed with [(h3-C3H5)PdCl]2, in the presence of a ferrocenylphosphine ligand (3 or 4).10

38

Bis(h3-allyl)dichlorodipalladium

X PPh2 PAr

M PPh2 X

(1)

(2) X = COOMe vs. X = CH2OR

P

PPh2 Fe

Ph Ph

PPh2

(3)

Fe Ph

Ph Ph

(4)

Coupling reactions. Recent works on coupling reactions mainly address variations of conditions, particularly new ligand and metal combinations. Suzuki coupling has now been conducted with Pd catalyst assisted by the carbene 1B,11 and Heck reaction in the presence of all-cis 1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane.12,13 Br

PPh2

PdCl

Ph Ph2P

PPh2

+

R

R 2

(1), K2CO2 DMF

Ph

Ph2P

(1) Alkenylation of benzoxazole and benzothiazole occurs at C-2 under Heck reaction conditions.14 Cross-coupling of ArX and Ar 0 Si(Me)2OK is improved by Ph3PO, which serves as a stabilizing ligand for the Pd catalyst.15 1

Kuriyama, M., Shimazawa, R., Shirai, R. JOC 73, 1597 (2008). Kuwano, R., Kusano, H. OL 10, 1979 (2008). 3 Yu, J.-Y., Kuwano, R. OL 10, 973 (2008). 4 Cheng, H.-Y., Sun, C.-S., Hou, D.-R. JOC 72, 2674 (2007). 5 Narumi, T., Tomita, K., Inokuchi, E., Kobayashi, K., Oishi, S., Ohno, H., Fujii, N. OL 9, 3465 (2007). 6 Johns, A.M., Liu, Z., Hartwig, J.F. ACIE 46, 7259 (2007). 7 Dubovyk, I., Watson, I.D.G., Yudin, A.K. JACS 129, 14172 (2007). 8 Hara, O., Koshizawa, T., Makino, K., Kunimune, I., Namiki, A., Hamada, Y. T 63, 6170 (2007). 9 Xie, F., Liu, D., Zhang, W. TL 49, 1012 (2008). 10 Vo, G.D., Hartwig, J.F. ACIE 47, 2127 (2008). 11 Kuriyama, M., Shimazawa, R., Shirai, R. T 63, 9393 (2007). 12 Fall, Y., Berthiol, F., Doucet, H., Santelli, M. S 1683 (2007). 13 Lemhadri, M., Battace, A., Berthiol, F., Zair, T., Doucet, H., Santelli, M. S 1142 (2008). 14 Gottumukkala, A.L., Derridj, F., Djebbar, S., Doucet, H. TL 49, 2926 (2008). 15 Denmark, S.E., Smith, R.C., Tymonko, S.A. T 63, 5730 (2007). 2

Bis(benzonitrile)dichloropalladium(II)

39

Bis[(h6-arene)dichlororuthenium(II)]. Arylation. Benzalimino compounds are o-activated for arylation by a combination of [(h6-cymene)RuCl2]2 and mesitylenecarboxylic acid.1 Carbenoid insertion.2 The Ru complex is also effective in forming metal-carbenoids from diazoalkanes for insertion into XZH bonds, as exempliﬁed by the formation of proline derivatives. O

O R'

[(p-cymene)RuCl2]2

COOR"

R'

MeOH

NH N2

COOR"

N R

R 1

Ackermann, L., Vicente, R., Althammer, A. OL 10, 2299 (2008). Deng, Q.-H., Xu, H.-W., Yuen, A.W.-H., Xu, Z.-J., Che, C.-M. OL 10, 1529 (2008).

2

Bis(benzonitrile)dichloropalladium(II). Coupling reactions. Under catalysis of (PhCN)2PdCl2 Negishi coupling performs better with diphenyl(o-chalconyl)phosphine, which is a p-acceptor ligand.1 Teraryls are readily synthesized from 1,4-bis(iodozincio)benzene by consecutive Negishi coupling reactions. Such is feasible because of the different reactivity of the two types of arylzinc reagents, products of the ﬁrst coupling are less reactive toward the Pd catalyst.2 Ar

ZnI

Ar

ArI (PhCN)2PdCl2

Ar'I

t-Bu3P, TMU

[Pd]

THF

ZnI

ZnI

Ar'

Heck reaction intermediates are intercepted as chlorides by either PhICl2 or CuCl2, with interesting regiochemical consequences.3 Cl

PhSnBu3

(PhCN)2PdCl2

+

Ph

Ph

oxidant

+ R

R Cl

R oxidant:

PhICl2/CH2Cl2 CuCl2/Et2O

>6 : 1 <1 : 20

Isomerization. Overman rearrangement of imino ethers of glycals favors the generation of b-glycosyl amides.4 Interestingly, more ionic Pd species favor the a-isomers.

40

Bis[bromotricarbonyl(tetrahydrofuran)rhenium]

(RO)n O

(MeCN)4Pd(BF4)2 o-HOC6H4CHO

(RO)n HN

O

H

NHCOCCl3

O

CCl3

(RO)n O

(PhCN)2PdCl2 o-HOC6H4CHO

NHCOCCl3

H

Allenyl ketones undergo cycloisomerization on exposure to (PhCN)2PdCl2. Dimeric products are produced if an a-substituent (at the allenyl group) is absent from the substrates.5 R

O (PhCN)2PdCl2

R'

C

R

O

R

O

R'

R

O

(PhCN)2PdCl2

C

O R

1

Luo, X., Zhang, H., Duan, H., Liu, Q., Zhu, L., Zhang, T., Lie, A. OL 9, 4571 (2007). Kawamoto, T., Ejiri, S., Kobayashi, K., Odo, S., Nishihara, Y., Takagi, K. JOC 73, 1601 (2008). 3 Kalyani, D., Sanford, M.S. JACS 130, 2150 (2008). 4 Yang, J., Mercer, G.J., Nguyen, H.M. OL 9, 4231 (2007). 5 Alcaide, B., Almandros, P., del Campo, T.M. EJOC 2844 (2007). 2

Bis[bromotricarbonyl(tetrahydrofuran)rhenium]. [212]Cycloadditions. Norbornene and norbornadiene undergo cycloaddition with alkynes from the exo-face. 2,6-Diisopropylphenyl isocyanide is provided as a ligand for the Re catalyst.1 1

Kuninobu, Y., Yu, P., Takai, K. CL 36, 1162 (2007).

Bis[chloro(1,5-cyclooctadiene)iridium(I)]. Addition reactions. Catalyzed by [(cod)IrCl]2 –BIPHEP, carboxylic acids (as cesium salts) add to the more highly substituted double bond of 1,1-dimethylallene to give a,adimethylallyl esters.1

Bis[chloro(1,5-cyclooctadiene)iridium(I)]

41

From [(cod)IrCl]2 the pincer complex 1 is prepared. It is stable to air and water, and shows catalytic activity for hydroamination (e.g., to form pyrrolidine and piperidine derivatives).2

N N Bu

(Me2N)4Zr;

N +N

Bu

N 2I

–

N M

[(cod)MCl]2

I

Bu N

N+ Bu

I I M

N Bu

I

Bu N

N

N

(1) A more valuable synthetic method based on the Ir(I) complex is the stereoselective addition of alcohols to dienes to afford homoallylic alcohols.3

OH

H

[(cod)IrCl]2

+ R

OH R

ClCH2CH2Cl 65°

(syn : anti >95 : 5)

In derivatization of nucleophilic allylstannanes from allylic alcohols and SnCl2 for the addition to carbonyl compounds, [(cod)IrCl]2 shows superior performance than [(cod)RhCl]2 and (PhCN)2PdCl2.4 Redox cyclization. Allylic alcohol and alkyne units that are separated by several bonds undergo cyclization that involves hydrogen transfer to the triple bond and appearance of a formyl group.5 The products also can participate in aldol-type condensation.

R Z

[(cod)IrCl]2 THF

CHCH2OH

R

R Z

Z CHO

COOR' CN

Borylation. Directed by a silylated heteroatom the borylation opens a new trail for o-functionalization of arenes.6 Allylic boranes derived from alkenes by the same protocol can be used to synthesize homoallylic alcohols and alkenylarenes.7

42

Bis[chloro(1,5-cyclooctadiene)iridium(I)]

Z

SiMe2H

Z

[(cod)IrCl]2

+ O B O

B O O

N

B O O

H [(cod)IrCl]2

+

O B O

SiMe2H

OH Ar

DBU; ArX

B O O

Ar (X = I)

(X = CHO)

Borylation at the terminal sp 2-carbon atom of allylsilanes with bis(pinacolato)diboron furnishes a valuable reagent for homologation and/or functionalization by two different reactions.8 Esters. Various esters are obtained by mixing RCHO and alcohols with [(cod)IrCl]2 and K2CO3 at room temperature. In the case of allyl alcohol some propyl esters are also formed.9 Primary alcohols RCH2OH are oxidized to provide esters RCOOCH2R on heating with [(cod)IrCl]2 in open air (958).10 3,5-Disubstituted benzoic esters arise from an Ir-catalyzed [2þ2þ2]cycloaddition involving propynoic esters and two equivalents of 1-alkynes. Aryl ethynyl sulfones also react similarly.11 MeOOC

COOMe [(cod)IrCl]2

+ R

R

P(C6F5)2 P(C6F5)2

R

R

Substitution. Secondary allylic alcohols are converted to amines by reaction with sulfamic acid, which forms the internal salt [Me2NvCHOSO3] and NH3 to provide both activator and nucleophile.12 1

Kim, I.S., Krische, M.J. OL 10, 513 (2008). Bauer, E.B., Andavan, G.T.S., Hollis, T.K., Rubio, R.J., Cho, J., Kuchenbeiser, G.R., Helgert, T.R., Letko, C.S., Tham, F.S. OL 10, 1175 (2008). 3 Bower, J.F., Patman, R.L., Krische, M.J. OL 10, 1033 (2008). 4 Masuyama, Y., Marukawa, M. TL 48, 5963 (2007). 5 Kummeter, M., Ruff, C.M., Mu¨ller, T.J.J. SL 717 (2007). 6 Boebel, T.A., Hartwig, J.F. JACS 130, 7534 (2008). 7 Olsson, V.J., Szabo, K.J. ACIE 46, 6891 (2007). 8 Olsson, V.J., Szabo, K.J. OL 10, 3129 (2008). 2

Bis[chloro(1,5-cyclooctadiene)rhodium(I)]

43

9

Kiyooka, S., Wada, Y., Ueno, M., Yokoyama, T., Yokoyama, R. T 63, 12695 (2007). Izumi, A., Obora, Y., Sakaguchi, S., Ishii, Y. TL 47, 9199 (2006). 11 Onodera, G., Matsuzawa, M., Aizawa, T., Kitahara, T., Shimizu, Y., Kozuka, S., Takeuchi, R. SL 755 (2008). 12 Deﬁeber, C., Ariger, M.A., Moriel, P., Carreira, E.M. ACIE 46, 3139 (2007). 10

Bis[chloro(1,5-cyclooctadiene)rhodium(I)]. Hydrogenation. With bis(dibenzotropyl)amine and a phosphine as coligands to modify [(cod)RhCl]2 a hydrogenation catalyst is formed. Reduction of alkenes and ketones with this system employs EtOH as hydrogen source.1 Addition reactions. Alkenylsilanes2 and alkenylboronic acids3 are converted into Rh reagents, which add to conjugated carbonyl compounds. O

Si N

H

O

[(cod)RhCl]2

N

dioxane 30°

OTBS H

OBn

O [(cod)RhCl]2

+

OBn

O

LiOH

(HO)2B

OTBS

OBn

H

OBn 95%

Azolecarbene complexes derived from the title reagent are found to convert alkenes into homologous saturated amines via hydroformylation and reductive amination in one operation.4 Chloroformates and 1-alkynes combine to give (Z)-2-chloroalkenoic esters.5 Cycloisomerization. Molecules containing two allene units that are separated by four bonds undergo Rh-catalyzed cycloisomerization. Unsaturated 7-membered ring compounds with two exocyclic double bonds are produced.6 C

[(cod)RhCl]2

Z C

R

R Z = O, NTs, CR2

MeCN

Z

R R

o-Ethynylarylamines and phenols cyclize to indoles and benzofurans, respectively, by heating with [(cod)RhCl]2 and an Ar3P in DMF at 858.7 The presence of either electrondonating or electron-withdrawing substituent(s) in the aromatic moiety has little effect.

44

Bis[chloro(1,5-cyclooctadiene)rhodium(I)]

Elimination of Ar2CO. b,b-Diphenyl-b-hydroxy ketones suffer cleavage to generate Rh enolates, which can be trapped in situ, for example, with RCHO.8 OH O Ph Ph

OH O

[(cod)RhCl]2

+ RCHO

TMEDA, Cs2CO3

R

dioxane 20°

More signiﬁcantly, a triarylmethanol also lose Ar2CO and the remaining aryl group is benzannulated by reaction with two equivalents of an alkyne.9 HO Ar Ar

R

R

R

[(cod)RhCl]2

+

H

Cu(OAc)2,

R

Ph

Ph

Ph

Ar

O Rh X

R

Ar O

Ar

Ar

R

Ph

RhX R

R

Decarbonylation and carbonylation. 1,1-Diarylethanes (of particular interest are the chiral members) are obtained from decarbonylation of 3,3-diarylpropanals. Such compounds are accessible from cinnamaldehydes in two steps, involving two different Rh-catalyzed reactions.10 Ar

CHO

[(cod)RhCl]2

*

DPPP CF3CH2OH 140°

Ar'

Ar

* Me

Ar'

CHO + Ar'

Ar'B(OH)2

Co-entrapment of [(cod)RhCl]2, a sulfonated tertiary phosphine and ionic liquid in silica gel forms a hydroformylation catalyst that is shown to exhibit very high (usually .95%) selectivity for converting styrenes into a-arylacetaldehydes.11 Insertion of CO into the OC bond of an oxazolidine gives morpholinones.12 Cyclopropanes are particularly susceptible to CO insertion via rhodacyclobutane intermediates. Spiro[2.2]pentanes in which the two rings have different degrees of substitution show selective transformations.13 Cyclopropylcyclopropanes give 4-cycloheptenones.14

Bis[chloro(1,5-cyclooctadiene)rhodium(I)]

COOEt R

N

[(cod)RhCl]2

O

KI CO–H2

45

Me N

R

O

2° cleavage

O

O [(cod)RhCl]2

R

R

CO/DPPP p-xylene 130°

R'

R'

1° cleavage

TsN [(cod)RhCl]2

TsN

CO PhMe 100°

O 44%

The [(cod)RhCl]2 complex can be used as a catalyst for the Pauson–Khand reaction under CO.15 The true catalyst may be formed by exchange of the two ligands (to CO and DPPP).16 R

R

O

[(cod)RhCl]2

N

C

NR'

NR'

CO/DPPP PhMe

N R = Ph, R' = Pr 77%

C

OMOM OPiv

[(cod)RhCl]2 CO/DPPP PhMe

OMOM

O

OPiv 96%

Arylation of arenes. On transforming [(cod)RhCl]2 into a more active cationic Rh(I) species by di(2-pyridyl)aminodiphenylphosphine, reaction between ArX and Ar 0 H occurs in its presence to give Ar-Ar 0 .17 1

Zweifel, T., Naubron, J.-V., Bu¨ttner, T., Ott, T., Gru¨tzmacher, H.-G. ACIE 47, 3245 (2008). Furman, B., Lipner, G. T 64, 3464 (2008). 3 Wu, Y., Gao, J. OL 10, 1533 (2008). 4 Ahmed, M., Buch, C., Routaboul, L., Jackstell, R., Klein, H., Spannenberg, A., Beller, M. CEJ 13, 1594 (2007). 2

46

Bis[chloro(dicyclooctene)rhodium(I)]

5

Baek, J.Y., Lee, S.I., Sim, S.H., Chung, Y.K. SL 551 (2008). Lu, P., Ma, S. OL 9, 2095 (2007). 7 Trost, B.M., McClory, A. ACIE 46, 2074 (2007). 8 Murakami, K., Ohmiya, H., Yorimitsu, H., Oshima, K. TL 49, 2388 (2008). 9 Uto, T., Shimizu, M., Ueura, K., Tsurugi, H., Satoh, T., Miura, M. JOC 73, 298 (2008). 10 Fessard, T.C., Andrews, S.P., Motoyoshi, H., Carreira, E.M. ACIE 46, 9331 (2007). 11 Hamza, K., Blum, J. EJOC 4706 (2007). 12 Vasylyev, M., Alper, H. OL 10, 1357 (2008). 13 Matsuda, T., Tsuboi, T., Murakami, M. JACS 129, 12596 (2007). 14 Kim, S.Y., Lee, S.I., Choi, S.Y., Chung, Y.K. ACIE 47, 4914 (2008). 15 Saito, T., Sugizaki, K., Otani, T., Suyama, T. OL 9, 1239 (2007). 16 Hirose, T., Miyakoshi, N., Mukai, C. JOC 73, 1061 (2008). 17 Proch, S., Kempe, R. ACIE 46, 3135 (2007). 6

Bis[chloro(dicyclooctene)rhodium(I)]. Coupling reactions. Alkylation of heteroaromatic compounds at a site adjacent to the heteroatom (e.g., N) by alkenes in the presence of [(coe)2RhCl]2 is validated for pyridines and quinolines.1 For more conventional arylation with ArBr the catalyst system containing a phosphepine ligand (1) is recommended.2

P

(1) Cycloisomerization. Activation of a CZH bond by the Rh complex for intramolecular hydrometallation of a proximal double bond can lead to valuable cyclic products. Examples for such reactions include elaboration of dehydrobenzosuberones from o-formylbenzylidenecyclopropanes3 and of cyclopentane derivatives through addition of an azadiene.4,5 CHO

O [(coe)2RhCl]2 p-An3P

TBSO COOEt [(coe)2RhCl]2

TBSO NMe

Me2N

COOEt

PEt2

PhMe 45°

NMe

Bis[chloro(norbornadiene)rhodium(I)]

47

O-Silylation. Using [(coe)2RhCl]2 as catalyst ROH are silylated by vinylsilanes.5 1

Lewis, J.C., Bergman, R.G., Ellman, J.A. JACS 129, 5332 (2007). Lewis, J.C., Berman, A.M., Bergman, R.G., Ellman, J.A. JACS 130, 2493 (2008). 3 Aissa, C., Fu¨rstner, A. JACS 129, 14836 (2007). 4 Tsai, A.S., Bergman, R.G., Ellman, J.A. JACS 130, 6316 (2008). 5 Park, J.-W., Jun, C.-H. OL 9, 4073 (2007). 2

Bis[chloro(diethene)rhodium(I)]. Coupling reactions. 2-Arylpyridines can be arylated by ArB(OH)2, with the Rh complex and the presence of tris( p-triﬂuoromethylphenyl)phosphine and TEMPO.1 Heck reaction involving ArBF3K with the Rh complex (and Ph3P) does not require any base.2 Vinyl and alkenyl groups attached to the silicon atom of the o-hydroxyphenylsilanes are transferred to b-silyl enones on mediation of [(C2H4)2RhCl]2, and the transfer can be rendered enantioselective by adding chiral ligands such as 2,5-diphenylbicyclo[2.2.2]octa2,5-diene.3 HO R

R

[(C2H4)2RhCl]2

Si + R'

O

Ph Ph

O

Si

R'

Si

R"

R"

In arylation of N-tosylaldimines by ArB(OH)2 the diene ligand is a diphenyltetrahydropentalene.4 1

Vogler, T., Studer, A. OL 10, 129 (2008). Martinez, R., Voica, F., Genet, J.-P., Darses, S. OL 9, 3213 (2007). 3 Shintani, R., Ichikawa, Y., Hayashi, T., Chen, J., Nakao, Y., Hiyama, T. OL 9, 4643 (2007). 4 Wang, Z.-Q., Feng, C.-G., Xu, M.-H., Lin, G.-Q. JACS 129, 5336 (2007). 2

Bis[chloro(norbornadiene)rhodium(I)]. Coupling reactions. Alkynyl epoxides react with organoboronic acids by a formal SN20 process, yielding allenyl carbinols.1

O

+

PhB(OH)2

[(nbd)RhCl]2

C

KOH/THF

OH

Ph

48

Bis[chloro(pentamethylcyclopentadienyl)methylthioruthenium] triﬂate

Cycloaddition. A process leading to formation of a 1,3,6-cyclooctatriene system from a conjugated diene and two alkynes is useful. A cationic Rh(I) complex fulﬁlls the catalytic purpose.2 R' (CH2)n

R' [(nbd)RhCl]2

+

(CH2)n

AgSbF6

R

R

Me-DuPhos

1

Miura, T., Shimada, M., Ku, S.-Y., Tamai, T., Murakami, M. ACIE 46, 7101 (2007). DeBoef, B., Counts, W.R., Gilbertson, S.R. JOC 72, 799 (2007).

2

Bis[chloro(pentamethylcyclopentadienyl)methylthioruthenium] triﬂate. Enyne synthesis. Ethynyl cyclopropyl carbinols undergo dehydrative metallation on exposure to the Ru complex, the metallocarbenoids thus formed are attacked by common nucleophile (e.g., H2O, ArNH2) at a cyclopropyl carbon.1 The different carbenoids originated from ynoxy triﬂates engage in ipso-substitution.2 *Cp

+

Cp*

Ru Ru X Cl MeS SMe TfO

Ar

Ar HO (1A)

R

C

C

[Ru]

R

– ZH2

(1A) X = OH2 (1B) X = Cl

Ar R ZH

O Ar

ZH

(1B)

Ar 1

Yamauchi, Y., Onodera, G., Sakata, K., Yuki, M., Miyaka, Y., Uemura, S., Nishibayashi, Y. JACS 129, 5175 (2007). 2 Yamauchi, Y., Yuki, M., Tanabe, Y., Miyaka, Y., Inada, Y., Uemura, S., Nishibayashi, Y. JACS 130, 2908 (2008).

Bis[(1,5-cyclooctadiene)hydroxyiridium]. Annulation. Synthesis of 1-indanols from o-acylarylboronic acids and conjugated dienes involves iridium cycles. While dienes bearing electron-donating or electron-withdrawing substituent(s) are successfully used, the participating double bond is electron-richer.

Bis[(1,5-cyclooctadiene)hydroxyrhodium]

O

49

O

N

N +

(HO)2B

H

[(cod)IrOH]2

OH

PhMe 80°

CHO

92%

1

Nishimura, T., Yasuhara, Y., Hayashi, T. JACS 129, 7506 (2007).

Bis[(1,5-cyclooctadiene)hydroxyrhodium]. Reduction. N-Sulfonyl imines are reduced by o-triorganosilylbenzyl alcohols, which is catalyzed by [(cod)RhOH]2.1 Addition reactions. The same reagent system is active in hydroarylation and hydroalkenylation of alkynes.2 The arylsilanes submit the addends and thereby are converted into benzoxasiloles.3

R' Si

OH R

[(cod)RhOH]2

+

PPh2

R"

PPh2

R

R' O

+ Si

R"

PhMe 100°

Alkynylsilanes also are active such that dienynes are formed by the reaction of bis(trimethylsilyl)ethyne with alkynes.3

Ar

Me3Si +

Ar

Ar'

Ar SiMe3 [(cod)RhOH]2

Ar

Ar'

Cy2P(CH2)4PCy2 KF, PhOH

Ar'

Ar'

A synthesis of aroylformic esters is based on the addition of ArB(OH)2 to cyanoformic esters, with H3BO3 acting as an additive for the reaction.4 Addition reations are followed by cyclization as situation prevails, as in the case of the addition of boronic acids to 4-hydroxy-2-alkynoic esters (to give 3-substituted furanones, regiochemically differentiated from the Pd-catalyzed reaction).5

50

Bis[(1,5-cyclooctadiene)hydroxyrhodium]

OH R R

R"OOC

+

[(cod)RhOH]2

R

O

O

R

dioxane–H2O

R'

(10 : 1) 100°

R'B(OH)2

Boronic acids submit the organic groups to o-alkynylaryl isocyanates to afford 3alkylideneoxindoles, the incoming group being cis-related to the carbonyl function.6 Bis(pinacolato)diboron reacts similarly, and apparently the cyclic adducts are available for Suzuki coupling to generate a library of oxindoles.7 R

R

O B

[(cod)RhOH]2

NCO

+

O

O

Cl

O O

Cl

N H

80°

B B O

O

2-Alken-6-yn-1-ones react with organoboronic acids to give 3-acylmethyl-1-cyclopentenes containing a 2-substituent arising from the boronic acid.8 R R

[(cod)RhOH]2

O

Et3N/MeOH

O R'

23°

+ R'B(OH)2

2-Alkylidene-1,3-dithiane S-oxides are receptive to addition of boronic acids.9

O

S

S R

1

+ ArB(OH)2

[(cod)RhOH]2

S

S

Ar

R

O

Nakao, Y., Takada, M., Chen, J., Hiyama, T., Ichikawa, Y., Shintani, R., Hayashi, T. CL 37, 290 (2008). Nakao, Y., Takeda, M., Chen, J., Hiyama, T. SL 774 (2008). 3 Horita, A., Tsurugi, H., Satoh, T., Miura, M. OL 10, 1751 (2008). 4 Shimizu, H., Murakami, M. CC 2855 (2007). 5 Alfonsi, M., Arcadi, A., Chiarini, M., Marinelli, F. JOC 72, 9510 (2007). 6 Miura, T., Takahashi, Y., Murakami, M. OL 9, 5075 (2007). 7 Miura, T., Takahashi, Y., Murakami, M. OL 10, 1743 (2008). 8 Chen, Y., Lee, C. JACS 128, 15598 (2006). 9 Yoshida, S., Yorimitsu, H., Oshima, K. SL 1622 (2007). 2

Bis(1,5-cyclooctadiene)nickel(0)

51

Bis[(1,5-cyclooctadiene)methoxyiridium(I)]. Borylation. Arenes1 (including thiophene2) are borylated by pinacolatoborane using [(cod)IrOMe]2 as catalyst. The remarkable feature of this reaction is m-substitution, through such unusually patterned aromatic compounds become available.3,4 R

R [(cod)IrOMe]2

X

+ R

N

O

O

CuX2

B B O

R X = Cl, Br

O

1

Kikuchi, T., Nobuta, Y., Umeda, J., Yamamoto, Y., Ishiyama, T., Miyaura, N. T 64, 4967 (2008). Chotana, G.A., Kallepalli, V.A., Maleczka Jr, R.E., Smith III, M.R. T 64, 6103 (2008). 3 Murphy, J.M., Liao, X., Hartwig, J.F. JACS 129, 15434 (2007). 4 Murphy, J.M., Tzschucke, C.C., Hartwig, J.F. OL 9, 757 (2007). 2

Bis[(1,5-cyclooctadiene)methoxyrhodium(I)]. Hydration. Nitriles are converted to amides at room temperature with aqueous NaOH and catalytic amounts of [(cod)RhOMe]2 –Cy3P.1 Condensation reactions. Nitriles activated through coordination to Rh become nucleophilic toward aldehydes in DMSO such that b-hydroxy alkanitriles are formed at room temperature.2 The Rh complex also promotes transfer reaction of an organoborane to conjugated esters, and those with additional bonding opportunities cyclic structures may be erected.3 NH2

CN

+ COOEt

Ar-BBN

[(cod)RhOMe]2

COOEt

PhMe 110°

Ar 1

Goto, A., Endo, K., Saito, S. ACIE 47, 3607 (2008). Goto, A., Endo, K., Ukai, Y., Irle, S., Saito, S. 2212 (2008). 3 Miura, T., Harumashi, T., Murakami, M. OL 9, 741 (2007). 2

Bis(1,5-cyclooctadiene)nickel(0). Addition to CvO bond. Excellent regioselective addition of organozinc reagents to one of the CvO group of a cyclic anhydride (see equation below) can be attributed to precoordination to the electronically more favorable double bond.1

52

Bis(1,5-cyclooctadiene)nickel(0)

O

O

H

Ni(cod)2

+

O H

Et2Zn

THF 0°

COOH

O Ar

Ar

In the reductive aldol reaction t-butyl acrylate is formally transformed into an enolate of the propanoate ester. Such a reaction requires PhI in addition to Ni(cod)2 and Et3B.2 O R

CHO

+

OH O

Ni(cod)2 Et3B, PhI

O

R

O

Unactivated conjugated dienes also undergo reduction with a hydrosilane in situ to form allylating nucleophiles.3 The double bond of the allyl residue has a (Z )-conﬁguration. R"'SiH 3 +

R

Ni(cod)2

OSiR"' R

OHC

R'

R"

N

R'

N ..

R"

Activation of the C-2 of 1-alkenes with the Ni complex and an azolecarbene enables preparation of a-substituted acrylamides by adding to isocyanate esters.4 A similar addition of 1-alkenes to ArCHO in the presence of Et3SiOTf is also reported.5 Involvement of either a double bond or a triple bond is shown to depend on the substitution status of the alkyne unit, to result in the formation of a common ring or macrocycle, due to preference of activation.6 MOMO

O

SiMe3 O (R = SiMe3)

MOMO MOMO

O

R O

OSiEt3 Et3SiH, Ni(cod)2

MOMO CHO OTBS

Mes N

OTBS

NMes ..

MOMO

O O

MOMO OSiEt3 (R = H)

OTBS

Bis(1,5-cyclooctadiene)nickel(0)

53

Addition to CC multiple bonds. Allenes are carboxylated at the central carbon by the Ni-catalyzed reaction with CO2, hydroxylation follows on subsequent exposure to oxygen.7

COOH

CO2/Ni(cod)2

C

THF 0°; O2, HCl, MeOH

OH

Conjugate addition to a,b-unsaturated ketones8 and esters9 by organoboron reagents is accomplished with intervention of Ni(cod)2. Such processes are also subject to asymmetric induction.7 R

O +

Ni(cod)2

O

(1)/PhMe

B O

N Bn

R

O

N Bn Ar O

Ar O

O Ar

O Ar

PPh

(1) Ar = 3,5-(t-Bu)2C6H3

Selective addition to one double bond of a cross-conjugated dienone is attributed to formation of the intermediate with the metal binding to both a h3-boroxyallyl ligand and a h1-allyl ligand prior to the allyl group transfer.10 The conjugate addition can use bis(pinacolato)diboron to prepare b-boryl esters and amides.11 1-Alkenes combine with conjugated aldehydes and ketones in the Michael reaction style when a silyl triﬂate is present to polarize the acceptors.12 (Note styrenes are activated at the b-carbon.) OSiEt3

O R'

R' R"

Ni(cod)2 Bu3P, Et3N

R +

R

OSiEt3 R'

R"

R"

or

Et3SiOTf

Ar

Reductive coupling involving alkynes and conjugated carbonyl compounds generate g,dunsaturated carbonyl compounds.13 Under somewhat different reaction conditions (mainly with respect to ligand) acrolein participates in the reaction and its formyl group becomes oxidized.14

54

Bis(1,5-cyclooctadiene)nickel(0)

H

+

OMe

Ni(cod)2

R'

O

O R

R'

THF MeOH

..

N

R

N

Alkenes such as norbornene and styrene, and also 1,3-dienes add alkynylsilanes, the latter at the terminal double bond to afford branched skipped enynes.15 Cyanoalkynes split and add to alkynes and allenes to generate conjugated enynes.16 i-Pr3Si i-Pr3Si

Ni(cod)2

+

R

Bu3P PhMe 25°

R R Ni(cod)2, Ph3B R"

CN

R'

R

R"

R'

R Ni(cod)2, Ph3B

CN

CN

C R'

R'

A highly efﬁcient preparation of crotonitrile is by HCN addition to 1,3-butadiene, catalyzed by Ni(cod)2 in the presence of the bis(diphenylphosphino)triptycene ligand 1.17 + HCN Ni(cod)2

dioxane

(1)

Ph2P

Ph2P

(1)

CN

The Ni(cod)2 – Me3P reagent is able to split R-CN (alkyl, alkenyl, and aryl nitriles) and deliver the two components to a triple bond. A Lewis acid facilitates the initial process by coordinating to the nitrogen atom of the nitrile.18 From allyl sulﬁdes the formation of p-allylnickel species determines the reaction course with alkynes.19 Coupling reactions. In the presence of Ni(cod)2 – Cy3P and CsF, cross-coupling between boronic esters and ArOMe can be achieved.20 The nickel complex supported by an azolecarbene under basic conditions smooths the preparation of ArSR from ArBr and RSH.21 C-Arylation of ketones catalyzed by

Bis(1,5-cyclooctadiene)nickel(0)

55

Ni(cod)2 – Diﬂuorphos affords much better enantiomer ratios than the reaction using (dba)2Pd.22 The Ni-catalyzed coupling is a superior method for the preparation of unsymmetrical 1,5-dienes, an allylic nucleophile being generated from fragmentation of a tertiary homoallylic alcohol.23 Ph Ni(cod)2

Ph

OAc

(EtO)3P

+

SiMe3

OH Pd(OAc)2 Ar3P, Cs2CO3

SiMe3

Ph SiMe3

Phthalimides undergo decarbonylative incorporation of alkynes to give isoquinolones.24 Pyridine N-oxides couple with alkynes to provide 2-alkenyl derivatives.25 With pyridines reaction also occurs but it requires a Lewis acid.26

Ni(cod)2 i-Pr3P/R'2 Zn

N

R R

+

R

N

R R

R

Ni(cod)2 i-Pr3P/Me3Al

N

R R

Also catalyzed by Ni(cod)2 is the coupling reaction involving arynes, alkenes, and boronic acids.27 O O OTf SiMe3

Ni(cod)2

+

Ph3P/CsF MeCN 40°

(HO)2B Ph

Ph 92%

Silacyclobutanes are alkenylated with ring opening, on treatment with 1-alkenes in the presence of Ni(cod)2 – Cy3P.28

56

Bis(1,5-cyclooctadiene)nickel(0)

R

R Si

Si

Ni(cod)2

+

Cy3P PhMe 100°

The modiﬁed 2 : 1 Ni-COD complex in which the metal also binds to an imidazolidene unit shows superior selectivity in the Suzuki coupling of polyﬂuoroarenes. For example, reaction of perﬂuorotoluene occurs at the p-position of the triﬂuoromethyl group.29 Cycloaddition. A notable application of the [2þ2þ2]cycloaddition of alkynes to form a benzene ring is the preparation of tetrahydrohexahelicenes.30 MeO MeO Ni(cod)2

MeO

Ph3P

MeO

THF 25°

53%

Other useful cycloadditions based on catalysis of the Ni(0) complex include [3þ2] and [3þ2þ2] versions, which produce cyclopentanes,31 4-alkenylimidazolidinones,32 and 5-alkylidene-1,3-cycloheptadienes,33 respectively.

NBn

R Ni(cod)2

+

R'

R

OHC

R'

(t-BuO)4Ti

O

O O Ni(cod)2 MesN

R' +

RN

NPh R'

R N

..

NMes

R"

R"

O

PhN— —C=O

RN

NPh R' R" COOEt

EtOOC +

SiMe3

Ni(cod)2 Ph3P

SiMe3

PhMe

SiMe3

Me3Si

Bis(1,5-cyclooctadiene)rhodium(I) salts

57

1,2-Dihydropyridines are formed by the Ni-catalyzed cycloaddition, each product being derived from two molecules of alkynes and an N-sulfonylaldimine.34 1

Rogers, R.L., Moore, J.L., Rovis, T. ACIE 46, 9301 (2007). Chrovian, C.C., Montgomery, J. OL 9, 537 (2007). 3 Sato, Y., Hinata, Y., Seki, R., Oonishi, Y., Saito, N. OL 9, 5597 (2007). 4 Schleicher, K.D., Jamison, T.F. OL 9, 875 (2007). 5 Ho, C.-Y., Jamison, T.F. ACIE 46, 782 (2007). 6 Chrovian, C.C., Knapp-Reed, B., Montgomery, J. OL 10, 811 (2008). 7 Aoki, M., Izumi, S., Kaneko, M., Ukai, K., Takaya, J., Iwasawa, N. OL 9, 1251 (2007). 8 Sieber, J.D., Morken, J.P. JACS 130, 4978 (2008). 9 Hirano, K., Yorimitsu, H., Oshima, K. OL 9, 1541 (2007). 10 Sieber, J.D., Liu, S., Morken, J.P. JACS 129, 2214 (2007). 11 Hirano, K., Yorimitsu, H., Oshima, K. OL 9, 5031 (2007). 12 Ho, C.-Y., Ohmiya, H., Jamison, T.F. ACIE 47, 1893 (2008). 13 Herath, A., Thompson, B.B., Montgomery, J. JACS 129, 8712 (2007). 14 Herath, A., Li, W., Montgomery, J. JACS 130, 469 (2008). 15 Shirakura, M., Suginome, M. JACS 130, 5410 (2008). 16 Nakao, Y., Hirata, Y., Tanaka, M., Hiyama, T. ACIE 47, 385 (2008). 17 Bini, L., Muller, C., Wilting, J., von Chrzanowski, L., Spek, A.L., Vogt, D. JACS 129, 12622 (2007). 18 Nakao, Y., Yada, A., Ebata, S., Hiyama, T. JACS 129, 2428 (2007). 19 Hua, R., Takeda, H., Onozawa, S., Abe, Y., Tanaka, M. OL 9, 263 (2007). 20 Tobisu, M., Shimasaki, T., Chatani, N. ACIE 47, 4866 (2008). 21 Zhang, Y., Ngeow, K.C., Ying, J.Y. OL 9, 3495 (2007). 22 Liao, X., Weng, Z., Hartwig, J.F. JACS 130, 195 (2008). 23 Sumida, Y., Hayashi, S., Hirano, K., Yorimitsu, H., Oshima, K. OL 10, 1629 (2008). 24 Kajita, Y., Matsubara, S., Kurahashi, T. JACS 130, 6058 (2008). 25 Kanyiva, K.S., Nakao, Y., Hiyama, T. ACIE 46, 8872 (2007). 26 Nakao, Y., Kanyiva, K.S., Hiyama, T. JACS 130, 2448 (2008). 27 Jayanth, T.T., Cheng, C.-H. ACIE 46, 5921 (2007). 28 Hirano, K., Yorimitsu, H., Oshima, K. JACS 129, 6094 (2007). 29 Schaub, T., Backes, M., Radius, U. JACS 128, 15964 (2006). 30 Tepley, F., Stara, I.G., Stary, I., Kollarovic, A., Lustinec, D., Krausova, Z., Fiedler, P. EJOC 4244 (2007). 31 Liu, L., Montgomery, J. OL 9, 3885 (2007). 32 Zhang, K., Chopade, P.R., Louie, J. TL 49, 4306 (2008). 33 Saito, S., Komagawa, S., Azumaya, I., Masuda, M. JOC 72, 9114 (2007). 34 Ogoshi, S., Ikeda, H., Kurosawa, H. ACIE 46, 4930 (2007). 2

Bis(1,5-cyclooctadiene)rhodium(I) salts. Hydrogenation. Catalyst derived from (cod)2RhOTf and the SEGPHOS analogue 1 is instrumental for hydrogenation of piperitenone to (-)-menthol via pulegone.1 O

O H2/(cod)2RhOTf O O O O

PAr2 PAr2

58

Bis(1,5-cyclooctadiene)rhodium(I) salts

Addition reactions. Hydroboration of styrenes with pinacolatoborane catalyzed by (cod)2RhBF4 furnishes benzylic boranes. The rate of addition is inﬂuenced by electronic effects of the nuclear substituents.2 Intramolecular hydroamination to afford 5- and 6-membered cyclic amines is also assisted by (cod)2RhBF4, together with a bidentate ligand such as 2 or 3.3 Cy2P

O P(NEt)2

NMe2

(2)

P(NEt)2

(3)

Reductive hydroxyalkylation starts with enynes under hydrogen (1 atm.) to give dienyl carbinols with a glyoxylic ester.4 Ethyne forms a rhodacyclopentadiene which serves as 1,3-butadienylating agent for N-sulfonyl imines.5 R +

(cod)2Rh

COOEt

PAr2 PAr2

MeO MeO

OH

+

[3,5-(F3C)2C6H3]B

2

R

H2/(cod)2RhOTf

COOEt CHO

–

[RhIII]

Cl, MeO-BIPHEP ArCOOH H2

R

R

NHSO2Ar

NSO2Ar

Indanes are formed in a Rh-catalyzed reaction of o-bis(3-oxoalkenyl)arenes with RB(OH)2.6 Formally, there is a conjugate transfer of the R group to one of the enone unit with an intramolecular Michael reaction to follow. O

R R R'

+

O

R"B(OH)2

O (cod)2RhBF4

O

Ba(OH)2 dioxane-H2O (10 : 1)

R' R"

Bis(1,5-cyclooctadiene)rhodium(I) salts

59

Cycloaddition. A synthesis of phthalides is based on a [2þ2þ2]cycloaddition of alkynes. The ligand (R)-Solphos is used in this case to complement (cod)2RhBF4.7 The elaboration of dioxotetrahydro[7]helicenes from bis-[2,20 -(propargyloxy)naphthyl]ethyne is also remarkable.8 Me N O O

PPh2 PPh2

N Me (R)-Solphos

Cyclization. Another pattern of cyclization for 1,5-diynes is revealed for the Rh-catalyzed process. The products have a ﬁve-membered ring adorned with the crossconjugated triene system.9

(cod)2RhBF4

Z

Segphos 1,2-cyclohexanedione CH2Cl4

Z

Z Z = CR2

Z = NBn

N-Propargylarylamines are transformed into 2-methylindoles via a Claisen rearrangement which is followed by an intramolecular hydroamination.10 R N

(cod)2RhBF4 DPPP (CF3)2CHOH

R'

R N

R'

Coupling reactions. Quaternary salts of gramine couple with organoboronic acids to provide indoles with a 3-benzyl or a 3-allyl group.11 1

Ohshima, T., Tadaoka, H., Hori, K., Sayo, N., Mashima, K. CEJ 14, 2060 (2008). Edwards, D.R., Hleba, Y.B., Lata, C.J., Calhoun, L.A., Crudden, C.M. ACIE 46, 7799 (2007). 3 Liu, Z., Hartwig, J.F. JACS 130, 1570 (2008). 4 Hong, Y.-T., Cho, C.-W., Skucas, E., Krische, M.J. OL 9, 3745 (2007). 5 Skucas, E., Kong, J.R., Krische, M.J. JACS 129, 7242 (2007). 6 Navarro, C., Csaky, A.G. OL 10, 217 (2008). 7 Tanaka, K., Osaka, T., Noguchi, K., Hirano, M. OL 9, 1307 (2007). 8 Tanaka, K., Kamisawa, A., Suda, T., Noguchi, K., Hirano, M. JACS 129, 12078 (2007). 2

60

Bis(dibenzylideneacetone)palladium(0)

9

Tanaka, K., Otake, Y., Hirano, M. OL 9, 3953 (2007). Saito, A., Kanno, A., Hanzawa, Y. ACIE 46, 3931 (2007). 11 de la Herran, G., Segura, A., Csaky, A.G. OL 9, 961 (2007). 10

Bis(dibenzylideneacetone)palladium(0). Arylation. Oxindole and ester enolates are arylated by ArX, with (dba)2Pd and a bulky phosphine ligand present,1,2 although in the case dealing with the esters [t-Bu3P . PdBr]2 is equally effective.3 An intramolecular version of such arylation pertains to formation of oxindoles.4 Br

Ph O

N Me

(dba)2Pd

O

Ph N

..

N Me

N

Coupling reactions. Preparation of oxindoles in which C-3 is fully substituted can be achieved by a Heck reaction, if the neopentyl s-palladium intermediates are coerced into another coupling reaction. In the context of a synthetic approach to physostigmine and related alkaloids it requires only to supply a cyanide source to complete the task.5 OMe

OMe (dba)2Pd

MeN

(S)-Difluorphos

I

MeN

K4Fe(CN)6

O

120°

O

CN

78% (72% ee)

Conversion of ArX to styrenes using the inexpensive divinyltetramethyldisiloxane an activator (KOSiMe3) is added to facilitate the Pd-catalyzed coupling.6 A procedure of Suzuki coupling in the presence of (dba)2Pd also prescribes the ruthenocene ligand 1.7

P Ru Ph Ph Ph

(1) Coupling of arynes with either simple ArI or 2-iodobiaryls leads to triphenylenes. The two different situations differ in terms of stoichiometry of the reactants (2 : 1 and 1 : 1, respectively).8

Bis[dicarbonylchlororhodium(I)]

61

(dba)2Pd

I

TfO

(o-Tol)P MeCN

SiMe3

+

92%

I

COOEt COOEt TfO

SiMe3

(dba)2Pd

+

(o-Tol)3P MeCN

66%

Two alkynes molecules are gathered by the Pd catalyst to react with dialkylamino(pinacolatoboryl)silanes, consequently 2,4-disubstituted siloles are produced.9

NEt2 R' Si R' + R

O

B

O

R (dba)2Pd Ph3P PhMe

R

Si R'

R'

a-(o-Nitroaryl)acrylic esters undergo reductive coupling, in the presence of CO, to afford 3-indolecarboxylic esters.10 1

Durbin, M.J., Willis, M.C. OL 10, 1413 (2008). Hama, T., Hartwig, J.F. OL 10, 1549 (2008). 3 Hama, T., Hartwig, J.F. OL 10, 1545 (2008). 4 Ku¨ndig, E.P., Seidel, T.M., Jia, Y., Bernardinelli, G. ACIE 46, 8484 (2007). 5 Pinto, A., Jia, Y., Neuville, L., Zhu, J. CEJ 13, 961 (2007). 6 Denmark, S.E., Butler, C.R. JACS 130, 3690 (2008). 7 Hoshi, T., Nakazawa, T., Saitoh, I., Mori, A., Suzuki, T., Sakai, J., Hagiwara, H. OL 10, 2063 (2008). 8 Liu, Z., Larock, R.C. JOC 72, 223 (2007). 9 Ohmura, T., Masuda, K., Suginome, M. JACS 130, 1526 (2008). 10 So¨derberg, B.C.G., Banini, S.R., Turner, M.R., Minter, A.R., Arrington, A.K. S 903 (2008). 2

Bis[dicarbonylchlororhodium(I)]. Coupling reactions. Electron-rich heteroarenes (furan, thiophene, indole, . . .) couple with ArI using a catalyst derived from [Rh(CO)2Cl]2 and [(CF3)2CHO]3P and Ag2CO3.1

62

Bis[dicarbonylchlororhodium(I)]

Cycloadditions. Many types of cycloaddition are found to be catalyzed by [Rh(CO)2Cl]2. The divergent reaction courses of 2-vinylcyclopropylalkenes due to stereochemical differences are synthetically signiﬁcant.2

H [Rh(CO)2Cl]2

TsN

PhMe 110°

TsN H H

[Rh(CO)2Cl]2

TsN

PhMe 90°

TsN H

A unique reorganization of the bicyclo[1.1.0]butane unit during its participation in an intramolecular cycloaddition has been recognized.3

H TsN

[Rh(CO)2Cl]2

TsN

R

DPPE PhMe 110°

R

H

Alkenylcyclopropanes and ethyne combine to give 1,4-cycloheptadienes. The rate of this [5þ2]cycloaddition is enhanced by a substituent at C-1, especially a heteroatomic group.4

R

[Rh(CO)2Cl]2

R

+

The commonly employed reagent for carbonylative Pauson– Khand reaction is Co2(CO)8, but [Rh(CO)2Cl]2 is a valuable catalyst. When a paste made of powdered 4Amolecular sieves and t-BuOH is added to absorb CO, conversion of the substrates is increased.5 A cycloctenone synthesis is based on the [5þ2þ1]cycloaddition in which alkenylcyclopropane, alkene, and CO are the participants.6 The reaction is carried out under CO and N2 (0.2 and 0.8 atm., respectively). Its synthetic potential is illustrated in an approach to hirsutene.7

Bis[dicarbonylchlororhodium(I)]

63

O

H [Rh(CO)2Cl]2 CO

H

OTBS

OTBS

HCl H2O

H

HO H

H

O H H

H hirsutene

Pauson –Khand reaction of alkynyl ketones in which an allenyl group is extended further from the a0 -position is intriguing. It has been found that one of the double bonds of the allene unit can be selected to participate by using certain transition metal catalysts besides modiﬁcation of the substrates.8 O

R

[Rh(CO)2Cl]2

O R

O

CO PhMe 90°

R'

C R'

O

R

Mo(CO)6

O

DMSO PhMe 90°

CHR' 0

Cycloisomerization. Conjugated alkynones bearing at the a -position an allenyl substituent (a0 -carbon usually quaternary) undergo cyclization to afford cyclopentenones.9 O

O R R'

1

R

[Rh(CO)2Cl]2

C

PhMe 23°

R'

Yanagisawa, S., Sudo, T., Noyori, R., Itami, K. T 64, 6073 (2008). Jiao, L., Ye, S., Yu, Z.-X. JACS 130, 7178 (2008). 3 Walczak, M.A.A., Wipf, P. JACS 130, 6924 (2008). 4 Liu, P., Cheong, P.H.-Y., Yu, Z.-X., Wender, P.A., Houk, K.N. ACIE 47, 3939 (2008). 2

64

Bis[dicarbonyl(cyclopentadienyl)iron]

5

Blanco-Urgoiti, J., Abdi, D., Dominguez, G., Perez-Castells, J. T 64, 67 (2008). Wang, Y., Wang, J., Su, J., Huang, F., Jiao, L., Liang, Y., Yang, D., Zhang, S., Wender, P.A., Yu, Z.-X. JACS 129, 10060 (2007). 7 Jiao, L., Yuan, C., Yu, Z.-X. JACS 130, 4421 (2008). 8 Brummond, K.M., Chen, D. OL 10, 705 (2008). 9 Brummond, K.M., Chen, D., Painter, T.O., Mao, S., Seifried, D.D. SL 759 (2008). 6

Bis[dicarbonyl(cyclopentadienyl)iron]. Carbodiimide formation. Deoxygenative dimerization of isocyanate esters occurs on heating with [CpFe(CO)2]2 in xylene.1 1

Rahman, A.K.F., Nicholas, K.M. TL 48, 6002 (2007).

Bis[dichloro(1,5-cyclooctadiene)hydridoiridium(II)]. Mannich reaction. Synthesis of b-amino ketones involving ArNH2 is accomplished in DMSO at room temperature in using the Ir complex as catalyst.1 When b-amino ketones are desired Mannich adducts should be formed from o-anisylamine, as they can be dearylated by oxidation with CAN. 1

Sueki, S., Igarashi, T., Nakajima, T., Shimizu, I. CL 35, 682 (2006).

Bis[dichloro( p-cymene)ruthenium(II)]. Cyclization. Diynes such as 1,6-diynes undergo cyclization with incorporation of a RCOOH molecule on warming with the Ru complex and a phosphine ligand.1 ROOC

ROOC (p-cymene)RuCl2

ROOC +

ROOC

(4-FC6H4)3P

R'COOH

DMAP dioxane 65°

R'COO

N-Alkylation. The Ru complex turns alcohols into alkylating agents for amines. The reaction of diols such as 1,5-pentanediol gives cyclic amines.2,3 1

Kim, H., Goble, S.D., Lee, C. JACS 129, 1030 (2007). Hamid, M.H.S.A., Williams, J.M.J. TL 48, 8263 (2007). 3 Hamid, M.H.S.A., Williams, J.M.J. CC 725 (2007). 2

Bis[dichloro(pentamethylcyclopentadienyl)iridium(II)]. Substitution. Alcohols are transformed into secondary and tertiary amines in the Ir-catalyzed reaction with an ammonium salt. Remarkably, the counter-anion of the ammonium salt determines the extent of N-alkylation.1

Bis[dichloro(pentamethylcyclopentadienyl)iridium(II)]

R

OH

[Cp*IrCl2]2

+

NH4X

(RCH2)2NH

NaHCO3

X = OAc X = BF4

+ R

NH4BF4

OH OH

trace 50–98%

+

65

(RCH2)3N 55–92% 2–9%

[Cp*IrCl2]2 NaHCO3

R

N H

N-Alkylation of primary and secondary amines is also accomplished.2 Oxidative amination.3 A different reaction pathway is adopted in the reaction of primary alcohols with hydroxylamine hydrochloride under the inﬂuence of [Cp IrCl2]2. Dehydrogenation of the alcohols (to form RCHO) and oximation are followed by a rearrangement step, which leads to RCONH2. Annulation. Aroic acids with a free o-position incorporate two equivalents of an alkynes to form a benzene ring. Decarboxylation is arrested if the catalyst is switched from [Cp IrCl2]2 to [Cp RhCl2]2 (also there is a change of the auxiliary metal salt).4 Ph Ph

[Cp*IrCl2]2 Ag2CO3

COOH

Ph

160°

Ph +

Ph

O

Ph

[Cp*RhCl2]2

O

Cu(OAc)2 · H2O

Ph

180°

Ph

2,3-Disubstituted indoles are obtained from a reaction of o-aminobenzyl carbinols or o-nitrobenzyl carbinols and a primary (preferably benzyl) alcohol.5 Redox transformation of various functional groups and proper condensation thereof lead to the results.

R OH NX2 X = H, O

R' +

R' HO

[Cp*IrCl2]2

R

KOH

N H

66

Bis[dichloro(pentamethylcyclopentadienyl)rhodium(II)]

1

Yamaguchi, R., Kawagoe, S., Asai, C., Fujita, K. OL 10, 181 (2008). Fujita, K., Enoki, Y., Yamaguchi, R. T 64, 1943 (2008). 3 Owston, N.A., Parker, A.J., Williams, J.M.J. OL 9, 73 (2007). 4 Ueura, K., Satoh, T., Miura, M. JOC 72, 5362 (2007). 5 Whitney, S., Grigg, R., Derrick, A., Keep, A. OL 9, 3299 (2007). 2

Bis[dichloro(pentamethylcyclopentadienyl)rhodium(II)]. Annulation. Starting from heteroatom-directed o-metallation, two molecules of alkynes are incorporation into the benzene ring to form naphthalenes.1

N

N

Ar

N

N Ar

[Cp*RhCl2]2

+

Ar

Cu(OAc)2

Ar

Ph

Ph

Ph

Ar

DMF

Ph

Ar

1

Umeda, N., Tsurugi, H., Satoh, T., Miura, M. ACIE 47, 4109 (2008).

2,20 -Bis(diphenylphosphino)-1,10 -binaphthyl and analogues. Copper complexes. Addition. In the presence of a chiral BINAP to coordinate with Cu(OTf)2 a useful catalyst for the addition of diorganozincs to N-(2-pyridinesulfonyl) aldimines is achieved.1 Grignard reagents perform enantioselective conjugate addition to a,b-unsaturated esters in the presence of a CuI complex of Tol-BINAP.2 1

Desrosiers, J.-N., Bechara, W.S., Charette, A.B. OL 10, 2315 (2008). Wang, S.-Y., Ji, S.-J., Loh, T.-P. JACS 129, 276 (2007).

2

Gold complexes. Cycloisomerization.1 Gold salts and complexes are popular catalysts for organic transformations because it is found that the metal has high afﬁnity to allenes and alkynes. A gold ion usually requires stabilization of a phosphine. As shown by the cyclization of 1,2,7-alkatrienes, BINAP and its congners are adequate ligands.

X

X

X AuCl

PAr2 PAr2

(1) Ar = 3,5-Me2C6H3

AgOTf

C

(1)

X

Palladium complexes.

67

Hydroamination.2 On complexing to (R)-xylyl-BINAP gold p-nitrobenzoate activates a double bond of an allene moiety to allow intramolecular attack by an amino group, asymmetrically. 1

Tasselli, M.A., Chianese, A.R., Lee, S.J., Gagne, M.R. ACIE 46, 6670 (2007). LaLonde, R.L., Sherry, B.D., Kang, E.J., Toste, F.D. JACS 129, 2452 (2007).

2

Iridium complexes. Hydrogenation. For asymmetric hydrogenation of 2-substituted quinolines to give the tetrahydro derivatives a catalyst is created from [(cod)IrCl]2 and dendrimers with a 5,50 -carboxamido-BINAP core for enhanced activity.1 Coupling reactions. The [(cod)IrCl]2 – BINAP specimen transforms allyl acetate into a p-allyliridium complex. Reaction with a primary alcohol or an aldehyde affords homoallylic alcohol in chiral form.2 OAc

+

OH R

OH

[(cod)IrCl]2

R

BINAP Cs2CO3, THF

The ability of Ir complexes in performing dehydrogenation/hydrogenation is exploitable in that a primary alcohol acts as an alkylating agent for certain Wittig reagents.3 An emerging aldehyde is intercepted by the Wittig reagent and hydrogenation of the resulting alkene completes the process. With a chiral BINAP ligand the iridium complex mediates hydrogen transfer while the hydrogenation step is rendered enantioselective. COOEt Ph

OH

+ Ph3P

[(cod)IrCl]2

Ph

COOET

(S)-BINAP PhMe

(87% ee) 1

Wang, Z.-J., Deng, G.-J., Li, Y., He, Y.-M., Tang, W.-J., Fan, Q.-H. OL 9, 1243 (2007). Kim, I.S., Ngai, M.-Y., Krische, M.J. JACS 130, 6340 (2008). 3 Shermer, D.J., Slatford, P.A., Edney, D.D., Williams, J.M.J. TA 18, 2845 (2007). 2

Palladium complexes. Alkylation. Acetals of enals serve as alkylating agents for t-butyl b-keto esters using a Pd complex of BINAP.1 With a cationic Pd complex of (R)-BINAP intramolecular addition of arylboronic acid moiety to a sidechain ketone leads to chiral, tertiary benzylic alcohols.2 Heck reaction. Cyclization with desymmetrization is shown to proceed in excellent yields and ee by the formation of tetralin derivatives.3

68

Platinum complexes.

MeO

Ph

Ph Pd(OAc)2

OMe

(R)-BINAP

Ph

OTf

Ph (98% ee)

With Ag3PO4 as additive for an intramolecular Heck reaction to form 3,3-disubstituted oxindoles considerable variation of enantioselectivity and direction of asymmetric induction is observed.4 1

Umebayashi, N., Hamashima, Y., Hashizume, D., Sodeoka, M. ACIE 47, 4196 (2008). Liu, G., Lu, X. JACS 128, 16504 (2006). 3 Machotta, A.B., Straub, B.F., Oestreich, M. JACS 129, 13455 (2007). 4 McDermott, M.C., Stephenson, G.R., Walkington, A.J. SL 51 (2007). 2

Platinum complexes. Aldol reaction.1 A cationic Pt(II) salt complexed to BINAP is active in catalyzing the Mukaiyama aldol reaction in DMF. However, ee are not as high as desired. 1

Kiyooka, S., Matsumoto, S., Kojima, M., Sakonaka, K., Maeda, H. TL 49, 1589 (2008).

Rhodium complexes. Kinetic resolution. A method for kinetic resolution of t-homoallylic alcohols is hinged on selective cleavage of one enantiomeric series of compounds by a Rh complex of chiral octahydro-BINAP.1 HO

Ar

HO

[(cod)RhOH]2

Ar

(R)-H8-BINAP PhMe 100°

Isomerization. Heating N-allylaziridines with (cod)2RhOTf and rac-BINAP causes migration of the double bond to produce (Z)-propenylaziridines.2 Addition reactions. By intramolecular hydroacylation in an ionic liquid, indanones are prepared in a Rh-catalyzed reaction, the metal ion in use is ligated to (R)-BINAP.3 The inﬂuence of a ligand on the Rh-catalyzed addition of RAlMe2 to 2-cycloalkenones can be quite profound. The 1,2-addition in the presence of BINAP is switched over to the 1,4-addition mode when the ligand is omitted.4 Chiral dibenzylacetic esters are accessible from conjugate addition of ArB(OH)2 to t-butyl a-benzylacrylates when protonation with B(OH)3 is rendered enantioselective, by the presence of a chiral BINAP.5 Ar'B(OH)2 + Ar

Ar'

(acac)Rh(C2H4)2 B(OH)3, (S)-BINAP

COOt Bu

Ar

COOt Bu H

Rhodium complexes.

69

A similar strategy of enantioselective protonation affords a-amino esters from synthesis involving conjugate addition of RBF3K to N-protected a-aminoacrylic esters.6 Asymmetry is directly established at the b-carbon of an a,b-unsaturated carbonyl compound during silyl group transfer from a (pinacolatoboryl)silane, which is catalyzed by a Rh-BINAP complex.7 Cycloaddition. Different versions of [2þ2þ2]cycloaddition are known to be induced by cationic Rh(I) salts with support of BINAP ligands.8,9 Diynes combining with enol ethers lead to products containing a new benzene ring,10 and ring fused dihydropyrans are formed from enynes and a-dicarbonyl compounds.11

O

O

OMe

(R)-H8-BINAP

OMe

O

O

(cod)2RhBF4

O

O

R R Z

R"O

R'

+

Z

rac-BINAP CH2Cl2

R

R Z

R'

(cod)2RhBF4

+

R"COX

X

(cod)2RhBF4

Z

(R)-H8-BINAP

O

ClCH2CH2Cl

R'

R"

R'

80°

Reorganizations. Insertion of [Rh] into a cyclobutanone unit can lead to interesting consequences. Dihydrocoumarins are obtained from 3-(o-hydroxyaryl)cyclobutanones.12 As metal migration occurs from the rhodacyclopentane intermediates to the aromatic ring, site-selective functionalization is achieved. R

[Rh]

R

[(cod)RhOH]2

O OH

(R)-p-Tol-BINAP PhMe 25°

O

O

R'

R'

R

O

O

Asymmetric rearrangement of alkenyl alkynyl carbinols with a chiral Rh-BINAP catalyst furnishes b-alkynyl ketones.13 The transformation is synthetically equivalent to

70

Rhodium complexes.

enantioselective conjugate addition of the alkynyl unit, saving the asymmetric induction delegated to a different operation.

Si

Si [(cod)RhOH]2

HO R

O

(R)-BINAP PhMe 60°

R'

R

R'

Rearrangement of dialkynylbenzyl alcohols gives 3-alkynylindanones.14 O

SiR3 HO

[(cod)RhOH]2 BINAP dioxane 50°

SiR3

R3Si

SiR3

Coupling reactions. Cyclization of 1,6-enynes and diynes with concomitant arylcoupling is realized using diaryl ketones (possessing a free o-CH).15 o-Acylarylrhodium hydride species are formed to initiate hydrometallation at the triple bond. R R TsN

RhBF4

TsN

(S)-BINAP

+ O

* O

Ph

Ph

Cyclization involving sp 2-sp coupling from an allylic alcohol and an ynoate segments that forms a cyclopentane ring substituted by two functional sidechains in adjacent positions is a key step in a synthesis of (-)-platensimycin.16 O

O [(cod)RhCl]2 (S)-BINAP AgSbF6

OH COOMe 1

MeOOC

CHO 91%

Shintani, R., Takatsu, K., Hayashi, T. OL 10, 1191 (2008). Tsang, D.S., Yang, S., Alphonse, F.-A., Yudin, A.K. CEJ 14, 886 (2008). 3 Oonishi, Y., Ogura, J., Sato, Y. TL 48, 7505 (2007). 4 Siewert, J., Sandmann, R., von Zezschwitz, P. ACIE 46, 7122 (2007). 2

Ruthenium complexes.

71

5

Frost, C.G., Penrose, S.D., Lambshead, K., Raithby, P.R., Warren, J.E., Gleave, R. OL 9, 2119 (2007). Navarre, L., Martinez, R., Genet, J.-P., Darses, S. JACS 130, 6159 (2008). 7 Walter, C., Oestreich, M. ACIE 47, 3818 (2008). 8 Tanaka, K. SL 1977 (2007). 9 Tanaka, K., Sagae, H., Toyoda, K., Noguchi, K., Hirano, M. JACS 129, 1522 (2007). 10 Hara, H., Hirano, M., Tanaka, K. OL 10, 2537 (2008). 11 Tanaka, K., Otake, Y., Sagae, H., Noguchi, K., Hirano, M. ACIE 47, 1312 (2008). 12 Matsuda, T., Shigeno, M., Murakami, M. JACS 129, 12086 (2007). 13 Nishimura, T., Katoh, T., Takatsu, K., Shintani, R., Hayashi, T. JACS 129, 14158 (2007). 14 Shintani, R., Takatsu, K., Katoh, T., Nishimura, Y., Hayashi, T. ACIE 47, 1447 (2008). 15 Tsuchikama, K., Kuwata, Y., Tahara, Y., Yoshinami, Y., Shibatas, T. OL 9, 3097 (2007). 16 Nicolaou, K.C., Edmonds, D.J., Li, A., Tria, G.S. ACIE 46, 3942 (2007). 6

Ruthenium complexes. Asymmetric hydrogenation. Hydrogenation of t-butyl b-ketoalkanoates with (binap)2RuCl2 is selective in the presence of the corresponding hexaﬂuoroisopropyl esters (which is practically unreduced).1 The turnover rates for the hydrogenation of several b-ketocarboxylic acid derivatives have been determined, hydrogenation of amides (pyrrolidine and piperidine . diethylamine) is generally more facile than esters.2 Fluorous BINAP ligands such as 1, prepared from the bromo-BINOL precursor(s), coordinate with RuCl2 to form reusable catalysts that have shown activities in hydrogenation of a-substituted acrylic esters and dehydroamino esters.3 RF3Si PPh2 PPh2 RF3Si

(1) RF = C8F17CH2CH2 In the presence of 2, aryl ketones in which the a-carbon carries a heteroatom substituent undergo hydrogenation diastereoselectively and enantioselectively.4 Ar

Ar P Cl N Ru N P Cl H2 Ar Ar

(2) Ar = 4-MeOC6H4

Ph

72

Silver complexes.

Catalysts constituting a C2-symmetric 1,2-diamine have been used to hydrogenate a-aryl aldehydes to yield chiral alcohols, under dynamic kinetic resolution conditions.5 Hydrogenation of the carbonyl group of acylsilanes with 3 (presence of t-AmOK or NaBH4 as activator) is applicable to acquisition of a-silyl allylc alcohols from conjugated acylsilanes.6 R Ar

Ar P Cl

R

N

Ru P Ar

N Cl H2 Ar

(3) Ar = 4-MeC6H4 1

Kramer, R., Bru¨ckner, R. ACIE 46, 6537 (2007). Kramer, R., Bru¨ckner, R. CEJ 13, 9076 (2007). 3 Horn, J., Bannwarth, W. EJOC 2058 (2007). 4 Arai, N., Ooka, H., Azuma, K., Yabuuchi, T., Kurono, N., Inoue, T. OL 9, 939 (2007). 5 Li, X., List, B. CC 1739 (2007). 6 Arai, N., Suzuki, K., Sugizaki, S., Sorimachi, H., Ohkuma, T. ACIE 47, 1770 (2008). 2

Silver complexes. Hydroxyalkylation. The complex of AgOTf with (S)-BINAP is used in enantioselective reaction of 3-trimethylsilyl-1,4-cyclohexadiene with ArCHO.1 It is important to note the regiochemical aspect in its application to unsymmetrical pronucleophiles. The products are converted into chiral benzhydrols on dehydrogenation with DDQ. OH

SiMe3

AgOTf

+

ArCHO

(S)-BINAP

Ar

A review on the use of AgX – BINAP complexes in synthesis has been written.2 1

Umeda, R., Studer, A. OL 10, 993 (2008). Yanagisawa, A., Arai, T. CC 1165 (2008).

2

[Bis(o-diphenylphosphinobenzylidene)ethanediamine]dichlororuthenium(II). Reduction.1 Under hydrogenation conditions the title ruthenium complex reduces an ester to a primary alcohol without affecting a double bond.

Bis(2-methoxyethyl)aminosulfur triﬂuoride, Deoxo-Fluor

73

COOMe N Cl N Ph Ru Ph P P Ph Cl Ph

H2

(1)/NaOMe, THF

OH

(1) 1

Saudan, L.A., Saudan, C.M., Debieux, C., Wyss, P. ACIE 46, 7473 (2007).

Bis(ethene)trispyrazolylboratoruthenium. Hydroamination.1 Derivatization of 1-alkynes into either imines or enamines by RNH2 and R2NH, respectively, in the anti-Markovnikov sense, is accomplished by heating the mixtures with TpRu(C2H4)2 and Ph3P in toluene at 1008. 1

Fukumoto, Y., Asai, H., Shimizu, M., Chatani, N. JACS 129, 13792 (2007).

Bis(iodozincio)methane. Homoenolate ions.1 Cyclopropyloxyzinc iodides are generated from a-sulfonyloxy carbonyl compounds on reaction with CH2(ZnI)2. 1

Nomura, K., Matsubara, S. CL 36, 164 (2007).

Bis(2-methoxyethyl)aminosulfur triﬂuoride, Deoxo-Fluor. Azides and nitriles. Carboxylic acids are activated (to form RCOF) by Deoxo-Fluor for conversion into acyl azides on reaction with NaN3. Nitriles are formed by slight variation of conditions. Usually DAST can be used but the latter reagent is thermally less stable.1 MeO

O

NSF3

2

i-Pr2NEt/CH2Cl2

R

N3

RCOOH + NaN3 (DMSO)

MeO 2

NSF3

Ph3P

R–CN

Et3N/CH2Cl2

Of particular interest is the reaction proﬁle of arylacetic acids that is dependent on an additive.2

74

Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulﬁde, Lawesson’s reagent MeO 2

NSF3

Ar–CN

i-Pr2NEt/CH2Cl2

ArCH2COOH + NaN3 (DMSO)

MeO 2

NSF3

Et3P

ArCH2CN

Et3N/CH2Cl2

1

Kangani, C.O., Day, B.W., Kelley, D.E. TL 48, 5933 (2007). Kangani, C.O., Day, B.W., Kelley, D.E. TL 49, 914 (2008).

2

Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulﬁde, Lawesson’s reagent. Benzothiazoles. Heating o-halobenzanilides with Lawesson’s reagent and Cs2CO3 in xylene leads to the formation of benzothiazoles.1 1

Bernardi, D., Ba, L.A., Kirsch, G. SL 2121 (2007).

Bismuth(III) sulfate. Friedel– Crafts reaction. Active arenes (phenols, aryl ethers, aryl sulﬁdes, . . .) are alkylated by N-tosyl aldimines (and benzylamines) such that 1,1-diarylalkanes result, with promotion by Bi2(SO4)3 –Me3SiCl.1 1

Liu, C.-R., Li, M.-B., Yang, C.-F., Tian, S.-K. CC 1249 (2008).

Bismuth(III) triﬂate. Rearrangement.1 Acetates of Baylis–Hillman adducts undergo 1,3-migration of the acetoxy group on heating with Bi(OTf)3 . 4H2O in MeCN. Substitution. The Lewis acidity of Bi(OTf)3 caters to use in activating electron-rich benzyl ethers and acetates to react with enol silyl ethers.2 By the same token, only the alcohols (instead of halides) are needed in allylation and benzylation of 1,3-dicarbonyl compounds.3 N-Alkylation of sulfonamides occurs at room temperature with benzylic, allylic and propargylic alcohols in the presence of Bi(OTf)3 and KPF6.4 Addition. Assistance is rendered by Bi(OTf)3 . 4H2O to aldehydes to convert them into homoallylic alcohols with allyltributylstannane, under microwave irradiation.5 Cyclization. Ionization of an allylic bromide in the presence of Bi(OTf)3, to trigger p-participation, leading to a cyclized product is expected.6

Bis(naphtho[2,1-c])azepines

R

R R'

Z

75

Bi(OTf)3

R'

Z

Br

Cyclization of 4-alkynoic acids to give enol lactones shows effects of a terminal substituent.7

COOH

R"

O

O

Bi(OTf)3

R R'

ClCH2CH2Cl

R R'

R"

O

O

R"

R R'

R" = H

R" = Ar

1

Olleivier, T., Mwene-Mbeja, T.M. T 64, 5150 (2008). Rubenbauer, P., Bach, T. TL 49, 1305 (2008). 3 Rueping, M., Nachtsheim, B.J., Kuenkel, A. OL 9, 825 (2007). 4 Qin, H., Yamagiwa, N., Matsunaga, S., Shibasaki, M. ACIE 46, 409 (2007). 5 Ollevier, T., Li, Z. EJOC 5665 (2007). 6 Hayashi, R., Cook, G.R. TL 49, 3888 (2008). 7 Komeyama, K., Takahashi, K., Takaki, K. CL 37, 602 (2008). 2

Bis(naphtho[2,1-c])azepines. Aldol reaction. Aldol reaction in the presence of the chiral N-prolylbis(naphtho[2,1c])azepine 1 is beneﬁted by high diastereoselectivity and enantioselectivity.1 Formation of 2-substituted 3-aryl-3-hydroxypropanals from aliphatic and aromatic aldehydes proceeds well when effectuated by 2.2 For accomplishing enantioselective nitroaldol reaction at room temperature the use of a complex derived from Cu(OAc)2 and the diamine 3 can be used.3

NHTf N O N

Ph NH

H

N Ph

HN

(1)

(2)

(3)

76

Bis(naphtho[2,1-c])azepines

Substitutions. Bis(naphtho[2,1-c])azepine 4 containing two bulky substituents directs enantioselective a-iodination of RCH2CHO with NIS.4 Quaternary ammonium salt 5 is a chiral phase-transfer agent with proven utility in the alkylation of glycine derivatives.5 F HO

F

C6F5

F

C6F5

Br +

NH

–

NBu2

C6F5

F

HO C6F5

F

(4)

(5)

F

Addition reactions. Another quaternary ammonium salt 6 promotes asymmetric replacement of the tosyl residue from a-aminoalkyl p-tolyl sulfones by a cyano group, via addition of KCN to the imines generated in situ.6 Michael reaction of a-substituted t-butyl cyanoacetates to t-butyl propynoate establishes a quaternary carbon center in the adducts. Excellent asymmetric induction is achieved by much more bulky ammonium salt.7 CF3

CF3 +

N CF3

(6)

CF3

Hydrazone 7 behaves as a bidentate ligand for zinc species. However, the steric effect of the BINAP moiety on organozinc addition to ArCHO is not sufﬁcient to give good ee of the adducts.8

Bis(naphtho[2,1-c])phosphepins

77

N N HO

(7) 1

Li, X.-J., Zhang, G.-W., Wang, L., Hua, M.-Q., Ma, J.-A. SL 1255 (2008). Kano, T., Yamaguchi, Y., Tanaka, Y., Maruoka, K. ACIE 46, 1738 (2007). 3 Arai, T., Watanabe, M., Yanagisawa, A. OL 9, 3595 (2007). 4 Kano, T., Ueda, M., Maruoka, K. JACS 130, 3728 (2008). 5 Kitamura, M., Arimura, Y., Shirakawa, S., Maruoka, K. TL 49, 2026 (2008). 6 Ooi, T., Uematsu, Y., Fujimoto, J., Fukumoto, K., Maruoka, K. TL 48, 1337 (2007). 7 Wang, M., Kitamura, M., Maruoka, K. JACS 129, 1038 (2007). 8 Arai, T., Endo, Y., Yanagisawa, A. TA 18, 165 (2007). 2

Bis(naphtho[2,1-c])phosphepins. Hydrogenation. The phosphepin ligands 1 and 2, constituting with Rh and Pd respectively, mediate asymmetric hydrogenation of enol carbamates1 and cyclic sulfamidates.2

P

P Ph

Fe P

(1)

(2)

The 2-pyridone unit in ligand 3 has a high tendency to associate through intermolecular hydrogen bonding. To this dimeric structure the binding of Rh creates a hydrogenation catalyst that performs well in propylene carbonate.3

O HN P

(3)

78

Bis(pentaﬂuorophenyl)[4-dimesitylphosphino-2,3,5,6-tetraﬂuorophenyl]borane

1

Enthaler, S., Erre, G., Junge, K., Michalik, D., Spaqnnenberg, A., Marras, F., Gladiali, S., Beller, M. TA 18, 1288 (2007). 2 Wang, Y.-Q., Yu, C.-B., Wang, D.-W., Wang, X.-B., Zhou, Y.-G. OL 10, 2071 (2008). 3 Scha¨ffner, B., Hotz, J., Verevkin, S.P., Bo¨rner, A. TL 49, 768 (2008).

Bis(pentaﬂuorophenyl)[4-dimesitylphosphino-2,3,5,6-tetraﬂuorophenyl]borane. Hydrogenation.1 The title reagent 1 activates molecular hydrogen such that imines and nitriles are saturated.

F

F C6F5

P

B C6F5 F

F

(1)

1

Chase, P.A., Welch, G.C., Jurca, T., Stephan, D.W. ACIE 46, 8050 (2007).

1,10 ;3,30 -Bispropanediyl-2,20 -diimidazolylidene. Reduction. The superelectron donor 1, readily prepared from imidazole and 1,3diiodopropane, reduces aryl halides1 and promotes desulfonylation2 in DMF. H

SO2Ph (1) / DMF;

N

N

N

N

H2O

Ph

(1)

Ph

Ph

N Ts

Ph

(1) / DMF; H2O

Ph

N H

Ph

1

Murphy, J.A., Zhou, S., Thomson, D.W., Schoenebeck, F., Mahesh, M., Park, S.R., Tuttle, T., Berlouis, L.E.A. ACIE 46, 5178 (2007). 2 Schoenebeck, F., Murphy, J.A., Zhou, S., Uenoyama, Y., Miclo, Y., Tuttle, T. JACS 129, 13368 (2007).

Bis(trialkylphosphine)palladium. Coupling reaction. Arylation on the silicon atom of a hydrosilane is shown to be catalyzed by (t-Bu3P)2Pd.1

Boron tribromide

H Ar Si R H

+

Ar'I

79

H Ar Si R

(t-Bu3P)2Pd Et3N/THF

Ar'

1

Yamanoi, Y., Taira, T., Sato, J., Nakamula, I., Nishihara, H. OL 9, 4543 (2007).

Borane-sulﬁdes. Reduction.1 Reduction of the carboxyl group of an a-amino acid without racemization can be carried out by the BH3 –Me2S complex on its TIPS derivative.

R

COOTIPS

R

BH3 · SMe2

OTIPS

R CHO H2O

TIPS N B O H

NHTIPS

HN TIPS

Selective reduction of an ester group adjacent to an alcohol is achieved.2

O

O

MeOOC

COOMe OH

BH3 · SMe2 NaBH4 (cat.) THF

O

O

COOMe OH OH

Amide synthesis.3 Limited amounts (0.35 equivalent) of the borane-dimethyl sulﬁde or THF complex promote condensation of carboxylic acids and amines. Hydroboration.4 Synthesis of of B-alkenylpinacolatoborons is achieved via reaction of 1-alkynes with the new complex obtained from admixture of BH3 . Me2S with (C6F5)3B, followed by treatment with pinacolborane. 1

Soto-Cairoli, B., de Pomar, J.J., Soderquist, J.A. OL 10, 333 (2008). Varugese, S., Thomas, S., Haleema, S., Puthiaparambil, T.T., Ibnusaud, I. TL 48, 8209 (2007). 3 Huang, Z., Reilly, J.E., Buckle, R.N. SL 1026 (2007). 4 Hoshi, M., Shirakawa, K., Okimoto, M. TL 48, 8475 (2007). 2

Boric acid. Amidation. Boric acid promotes condensation of carboxylic acids with amines by heating in toluene.1 1

Barajas, J.G.H., Mendez, L.Y.V., Kouznetsov, V.V., Stashenko, E.E. S 377 (2008).

Boron tribromide. Rearrangement. Tertiary N-benzylglycinamides are subject to [1,2]-rearrangement by consecutive treatment with BBr3 and Et3N to afford phenylalaninamide analogues.1 The transformation cannot be effected by replacing boron tribromide with boron triﬂuoride.

80

Boron triﬂuoride etherate

NMe2

Ar Ar

N

BBr3

CONMe2

+

N

–

B

Ar

Et3N

O

NMe2 NH

O

Br Br 1

Tuzina, P., Somfai, P. TL 48, 4947 (2007).

Boron triﬂuoride etherate. Substitution. With BF3 . OEt2 and CF3COOH as activators, aryltiazenes are converted to aryl azides.1 Friedel –Crafts propargylation of arenes can be accomplished with propargyl trichloroacetimidates in the presence of BF3 . OEt2 at room temperature.2 a-Acetoxyalkyl carboxamides/lactams form acyliminium species in contact with BF3 . OEt2, and they are intercepted by potassium organotriﬂuoroborates.3

AcO O

AcO

OAc

BF3 . OEt2

N Bn

OAc

R–BF3K

OAc

CH2Cl2 –78°

O

N Bn

R

Reaction of trisubstituted epoxides with alkynylalanes in the presence of BF3 . OEt2 occurs at the quaternary carbon site. Without the Lewis acid much more side products appear.4 O

OH

OH

OH

BF3 . OEt2

+ Ph

Ph

AlMe2

73%

Addition reactions. 2-Aryl-3-vinyl-2,3-dihydrobenzofurans are obtained from reaction of benzoxasilepins and ArCHO. Substituent effects of ArCHO set the trend for cis/trans-isomer variation of the products.5

+ O Si

ArCHO

BF3 . OEt2

Ar O

Also in the alkenyl group transfer from the triﬂuoroborate salts to dichloroalkyl aldimines BF3 . OEt2 plays an activating role.6

Boron triﬂuoride etherate

81

Cyclization and cycloreversion. Despite its adjacency to a carbonyl group a tertiary oxy substituent at C-3 of oxindoles undergoes ionization on exposure to BF3 . OEt2, and that interaction with an alkenyl chain leads to spirocyclic products.7 RO BF3 . OEt2

O

O

N H

N H

N-Protected tetrahydroisoquinolines are formed from N-acylcarbamates of 2-arylethylamines in two steps: Reduction with Dibal-H and cyclization by BF3 . OEt2.8 A tandem reaction sequence involving electrocyclization, azide capture, and Schmidt rearrangement is observed when certain cross-conjugated dienones and alkyl azides are treated with BF3 . OEt2.9 O

O BF3 · OEt2

Ph

–78°

+ N3

Ph

N

CH2Cl2

Ph 80%

Ph

Cycloadducts of 4-hydroxy-2-isoxazoline N-oxides with alkenes are decomposed by BF3 . OEt2. It takes much longer if silica gel is used to effect the cycloreversion (48 hr. vs. 1 hr.)10 O N O HO

R'

BF3 . OEt2

R"

CHCl3

R

N O

R' R"

R

The exposure of 2-Boc-aminomethylaziridines to BF3 . OEt2 results in 5-aminomethyl-2oxazolidinones. The three-membered heterocycle is replaced by a 5-membered and there is a loss of the t-butyl group.11 Intramolecular Friedel –Crafts alkylation forming a seven-membered ring by a formal Michael addition at the terminus of a 3-ethynyl-2-benzyl-2-cyclohexenone unit is made sterically possible by the presence of EtSH.12

O

OMe OMe

EtSH BF3 . OEt2

O

MeO

CH2Cl2 25°

94%

OMe

82

Boron triﬂuoride etherate

4,4-Diﬂuoro-3-buten-1-ylarenes afford a-tetralones on exposure to BF3 . OEt2 (1 equiv.) and catalytic quantitites of (MeCN)4Pd(BF4)2, with hydrolytic work up.13

R CF2

R BF3 . OEt2

O

(MeCN)4Pd(BF4)2 (CF3)2CHOH; H 2O

Vinyl sulﬁdes are stable to BF3 . OEt2 therefore Nazarov cyclization intermediates can be trapped by them to produce 2-organothio-bicyclo[2.2.1]heptan-7-ones.14 Rearrangements. Under microwave irradiation the Claisen rearrangement of N-allylanilines is effectively catalyzed by BF3 . OEt2. Other Lewis acids are much inferior catalysts under the same conditions.15 A signiﬁcantly different reaction proﬁle for isomeric diketo epoxides (as shown below) has been discovered.16

H O

O H

BF3 . OEt2

O

O

O

O OH

H O H

O

H

BF3 . OEt2

OH O

O O

OHC

Alkenylcyclopropenes pursue a reaction pathway on exposure to BF3 . OEt2 different from that observed when they are treated with Cu(OTf)2.17

Boron triﬂuoride etherate

83

Ph BF3 . OEt2

Ph

(trace H2O)

Ph

60%

Ph

Ph Cu(OTf)2

Ph Ph 98%

1,3-Oxy migration of propargylic alcohols and stabilization of the allenyl products by carbamoylation are performed by heating the alcohols and RNCO with a ruthenium complex (1) and BF3 . OEt2.18 R + R'N=C=O

R OH N N OC

O Ru CO

(1) PhMe 100°

BF3 . OEt2

CO

(1)

R C R

1

OCONHR'

Liu, C.-Y., Knochel, P. JOC 72, 7106 (2007). Li, C., Wang, J. JOC 72, 7431 (2007). 3 Vieira, A.S., Ferreira, F.P., Fiorante, P.F., Guadagnin, R.C., Stefani, H.A. T 64, 3306 (2008). 4 Zhao, H., Engers, D.W., Morales, C.L., Pagenkopf, B.L. T 63, 8774 (2007). 5 Jimenez-Gonzalez, L., Garcia-Munoz, S., Alvarez-Corral, M., Munoz-Dorado, M., Rodriguez-Garcia, I. CEJ 13, 557 (2007). 6 Stas, S., Tehrani, K.A. T 63, 8921 (2007). 7 England, D.B., Merey, G., Padwa, A. OL 9, 3805 (2007). 8 Kuhakarn, C., Panyachariwat, N., Ruchirawat, S. TL 48, 8182 (2007). 9 Song, D., Rostami, A., West, F.G. JACS 129, 12019 (2007). 10 Nishiuchi, M., Sato, H., Ohmura, H. CL 37, 144 (2008). 11 Moran-Ramallal, R., Liz, R., Gotor, V. OL 10, 1935 (2008). 2

84

Bromine

12

Majetich, G., Zou, G., Grove, J. OL 10, 85 (2008). Yokota, M., Fujita, D., Ichikawa, J. OL 9, 4639 (2007). 14 Mahmoud, B., West, F.G. TL 48, 5091 (2007). 15 Gonzalez, I., Bellas, I., Souto, A., Rodriguez, R., Cruces, J. TL 49, 2002 (2008). 16 Asahara, H., Kubo, E., Togaya, K., Koizumi, T., Mochizuki, E., Oshima, T. OL 9, 3421 (2007). 17 Shao, L.-X., Zhang, Y.-P., Qi, M.-H., Shi, M. OL 9, 117 (2007). 18 Haak, E. EJOC 788 (2008). 13

Bromine. Aza-transfer. Certain unsaturated t-butylaldimines are found to transfer the nitrogen moiety to the double bond on consecutive treatment with bromine and a base.1

CHO

Br2;

N

H

NaOH

N

H

86%

Von Braun degradation. The triphenyl phosphite complex of bromine (and other halogens) converts tertiary amides into nitriles.2 1

D’hooghe, M., Boelens, M., Piqueur, J., De Kimpe, N. CC 1927 (2007). Vaccari, D., Davoli, P., Spaggiari, A., Prati, F. SL 1317 (2008).

2

Bromopentacarbonylmanganese. Coupling reactions. Coordinative stabilization of the arylmanganese species by an imino nitrogen atom greatly facilitates their formation via metal insertion of an o-C-H bond. o-Functionalization of the aryl residue in a 2-arylimidazole by reaction with electrophiles such as PhCHO after treatment with Mn(CO)5Br meets expectation.1 MeN

MeN Mn(CO)5Br

N

N OSiEt3

ArCHO Et3SiH

H

Ar

Cycloaddition.2 b-Keto esters are found to participate in [2þ2þ2]cycloaddition in the enolic form with two equivalents of alkynes, using Mn(CO)5Br as catalyst. Ph O Ar

1

COOEt

Ph

COOEt

Mn(CO)5Br

+

Ar

Ar

Kuninobu, Y., Nishina, Y., Takeuchi, T., Takai, K. ACIE 46, 6518 (2007). Tsuji, H., Yamagata, K., Fujimoto, T., Nakamura, E. JACS 130, 7792 (2008).

2

Ar

t-Butanesulﬁnamide

85

N-Bromosuccinimide, NBS. Debenzylation. A benzyl group attached to the nitrogen atom of a carboxamide is subject to removal by NBS at room temperature.1 Bromodesilylation. Alkenylsilanes are converted into the corresponding bromoalkenes by NBS.2 SiMe3

Ar

SiMe3

Br

NBS MeCN

Ar Br

66–90%

Bromination. In bromolactamization of unsaturated N-Boc amides with NBS in THF, adding the base t-BuOLi is recommended.3 a-Bromo enones are formed by treatment of enol silyl ethers with NBS under uv irradiation and in the presence of a free radical initiator (AIBN).4 The allylic position of an ordinary double bond, being less reactive, remains unaffected. OTIPS O COOMe

O NBS AIBN/CCl4 hv, 77°

O

Br

COOMe 75%

Another protocol for a-bromination of enals and cyclic enones using NBS indicates pyridine N-oxide to be a beneﬁcial additive.5 Amination. In a single step benzylic amination is achieved with NBS with catalytic amounts of FeCl2. Aminating agents include carboxamides and sulfonamides.6 N-Cyano sulﬁlimines are formed by reaction of sulﬁdes with cyanamide in the presence of NBS, probably involving S-bromination.7 1

Kuang, L., Zhou, J., Chen, S., Ding, K. S 3129 (2007). Pawluc, P., Hreczycho, G., Walkowiak, J., Marciniec, B. SL 2061 (2007). 3 Yeung, Y.-Y., Corey, E.J. TL 48, 7567 (2007). 4 Kraus, G.A., Jeon, I. TL 49, 286 (2008). 5 Bovonsombat, P., Rujiwarangkul, R., Bowornkiengkai, T., Leykajarakul, J. TL 48, 8607 (2007). 6 Wang, Z., Zhang, Y., Fu, H., Jiang, Y., Zhao, Y. OL 10, 1863 (2008). 7 Mancheno, O.G., Bistri, O., Bolm, C. OL 9, 3809 (2007). 2

t-Butanesulﬁnamide. Nitriles. Reaction of aldehydes with t-BuSONH2 in the presence of (EtO)4Ti and with microwave irradiation leads to nitriles.1 Resolution of 2,20 -diformylbiphenyls. The chiral sulﬁnamide forms separable diastereomeric imines with the biphenyldialdehyde, wherefrom optically active aldehydes are obtained.2

86

t-Butyl hydroperoxide

1

Tanuwidjaja, J., Peltier, H.M., Lewis, J.C., Schenkel, L.B., Ellman, J.A., S 3385 (2007). Zhu, C., Shi, Y., Xu, M.-H., Lin, G.-Q. OL 10, 1243 (2008).

2

t-Butyl hydroperoxide. Carboxamides. Because of the facility in benzylic oxidation for the adducts of ArCHO and secondary amines, their rapid conversion into ArCONR2 by t-BuOOH (metalfree conditions) is observed.1 1

Ekoue-Kovi, K., Wolf, C. OL 9, 3429 (2007).

t-Butyl hydroperoxide – metal salts. Oxidation. Oxidation of aldehydes to carboxylic acids by t-BuOOH (70%) with CuCl as catalyst occurs at room temperature.1 Using anhydrous t-BuOOH in decane, primary alcohols are also converted to the same products and secondary alcohols to ketones.2 More unusual is the oxidation of aldehydes in the presence of an alcohol to provide esters by t-BuOOH with both Cu(ClO4)2 and InBr3 as catalyst.3 The combination of TiCl4 and t-BuOOH constitutes an epoxidizing system (for allylic alcohols) at low temperature. However, it oxidizes the same substrates to enones in reﬂuxing CHCl3; and ordinary secondary alcohols to ketones, naturally.4 Another oxidizing system contains Rh2(cap)4,5 which also ﬁnds use in dehydrogenating secondary amines to form imines.6 A Pd-catalyzed oxidation to bring about ring closure is synthetically viable. Also noteworthy is that products containing different functional groups arise from a change of reaction conditions.7 Ac N O

Pd/C

NHAc

t-BuOOH; DBU

N H R 54% Ac N

NHSO2Et

OAc

Pd(OAc)2/C O2, NaOAc DMSO

N H R 75%

Epoxidation. New metal specimens for activating t-BuOOH to epoxidize alkenes include molybdenum oxide (with R3PO),8 and nanoparticles thereof.9 They have the advantage of being paramagnetic.

t-Butyl hydroperoxide – metal salts

87

The asymmetric epoxidation of allylic alcohols based on vanadyl isopropoxide and t-BuOOH has been reexamined with a series of chiral hydroamic acids (1).10

O

Ar3C

N OH

Ar =

N OH Ar3C

O

(1) g-(N-Sulfonylamino)propargylic alcohols undergo epoxidation but isomerization of the products to carbene species is rapid.11

Ts

OH N R

t-BuOOH

Ts N

O

OH R

VO(acac)2 CH2Cl2

R = H 40% Ts

OH N

t-BuOOH

Ph

VO(acac)2 CH2Cl2

Ts O N Bn

OH

81%

Cleavage of multiple CC bonds. Both alkenes and alkynes are cleaved by InCl3 – t-BuOOH in water.12 1

Mannam, S., Sekar, G. TL 49, 1083 (2008). Mannam, S., Sekar, G. TL 48, 2457 (2007). 3 Yoo, W.-J., Li, C.-J. TL 48, 1033 (2007). 4 Shei, C.-T., Chien, H.-L., Sung, K. SL 1021 (2008). 5 Choi, H., Doyle, M.P. OL 9, 5349 (2007). 6 Choi, H., Doyle, M.P. CC 745 (2007). 7 Beniazza, R., Dunet, J., Robert, F., Schenk, K., Landais, Y. OL 9, 3913 (2007). 8 Kiraz, C.I.A., Mora, L., Jimenez, L.S. S 92 (2007). 9 Shokouhimehr, M., Piao, Y., Kim, J., Jang, Y., Hyeon, T. ACIE 46, 7039 (2007). 10 Barlan, A.U., Zhang, W., Yamamoto, H. T 63, 6075 (2007). 11 Couty, S., Meyer, C., Cossy, J. SL 2819 (2007). 12 Ranu, B.C., Bhadra, S., Adak, L. TL 49, 2588 (2008). 2

88

Butyllithium

Butyllithium. X/Li Exchange. Different reactivities of polyhalogen substituents in an aromatic ring permit orderly exchange to form aryllithium species for stepwise functionalization.1

X'

X'

Li BuLi

BuLi; (RO)3B

B(OR)3Li

X

B(OR)3Li

Deprotonation. N0 -Boc arylhydrazines are deprotonated initially at the nitrogen atom of the carbamate group, but dianions are generated on treatment with 2 equivalents of BuLi. Selective dialkylation of the dianions can be accomplished.2 BuLi (1x);

Boc

RX

HN N R Ph

Boc HN NH Ph

Boc

R

BuLi (2x);

N N

RX; R'X

Ph

4-Alken-6-ynamines 2-allenylpyrrolidines.3

undergo

deprotonation;

an

BuLi

R

R'

ensuing

cyclization

affords

R R' HN

C R'N

Arsenic analogue of the Wittig reaction operates on diallylarsonium salts delivers 1,3-dienes. The internal double bond of the major products (from RCHO) has an (E)-conﬁguration.4

Ph As + Ph X

BuLi/THF-HMPA; RCHO

R

–

1,3,5-Trimethylperhydro-1,3,5-triazine is readily deprotonated to provide a synthetic equivalent of formyl anion. After addition of the lithiated species to carbonyl compounds a workup with HCl gives a-hydroxy aldehydes.5

Butyllithium – (-)-sparteine

89

Elimination. (E,E)-1,3-Dienamines are obtained from (Z)-4-methoxy-2-alkenylamines by treatment with BuLi (or NaHMDS). Elimination of MeOH is stereoselective.6 A preparation of triﬂuoromethylallenes from 1,1-dichloro-3,3,3-triﬂuoropropen-2-yl tosylate involves treatment with BuLi to generate lithium 3,3,3-triﬂuoropropynide, which is used for reaction with carbonyl compounds and then Negishi coupling.7

TsO Cl

CF3

CF3

CF3 R2CO

BuLi

Cl

R' R'ZnCl

OH

R

Li

C

[Pd0]

R

R

CF3

R

Dilithioethyne used for a synthesis of bis(pinacolato)ethyne is generated from trichloroethene with BuLi. The boronate has many synthetic applications.8 Brook rearrangement. a-Trimethylsilylpropargyl alcohols undergo Brook rearrangement to afford allenyl silyl ethers, which can be used to condense with aldehydes.9 Silyl group transfer from the ether four bonds apart is preferred after the Sn/Li exchange from silyl ethers of 1-tributylstannyl-1,3-alkanediols.10

R3SiO R"

OSiR'3 SnBu3

BuLi

HO R"

OSiR'3 SiR3

Addition. Hydroamination of cinnamyl alcohol occurs on exposure to amines that are deprotonated by BuLi. The products are vicinal amino alcohols.11 1

Kurach, P., Lulinski, S., Serwatowski, J. EJOC 3171 (2008). Bredihhin, A., Groth, U.M., Ma¨eorg, U. OL 9, 1097 (2007). 3 Zhang, W., Werness, J.B., Tang, W. OL 10, 2023 (2008). 4 Habrant, D., Stengel, B., Meunier, S., Mioskowski, C. CEJ 13, 5433 (2007). 5 Bojer, D., Kamps, I., Tian, X., Hepp, A., Pape, T., Fro¨hlich, R., Mitzel, N.W. ACIE 46, 4175 (2007). 6 Tayama, E., Sugai, S. TL 48, 6163 (2007). 7 Shimizu, M., Higashi, M., Takeda, Y., Jiang, G., Murai, M., Hiyama, T. SL 1163 (2007). 8 Kang, Y.K., Deria, P., Carroll, P.J., Therien, M.J. OL 10, 1341 (2008). 9 Reynolds, T.E., Scheidt, K.A. ACIE 46, 7806 (2007). 10 Mori, Y., Futamura, Y., Horisaki, K. ACIE 47, 1091 (2008). 11 Barry, C.S., Simpkins, N.S. TL 48, 8192 (2007). 2

Butyllithium – (-)-sparteine. Amines -> alcohols. A synthesis of secondary alcohols in chiral form from N-Boc secondary amines involves lithiation with the BuLi – (-)-sparteine complex, quenching with R3B, and decomposing the reaction mixture with NaOH–H2O2.1

90

s-Butyllithium

R

OH

BuLi, (-)-sparteine;

N Boc

R3B, Me3SiOTf;

NH Boc

H2O2, NaOH

1

Coldham, I., Patel, J.J., Raimbault, S., Whittaker, D.T.E., Adams, H., Fang, G.Y., Aggarwal, V.K. OL 10, 141 (2008).

s-Butyllithium. Lithiation. A synthesis of 1-biarylcarboxylic acids from aroic acids (selective arylation) is based on o-lithiation by s-BuLi, Li/Sn exchange, and Stille coupling.1 Selective functionalization at the methyl group of o-tolylmethanol via lateral lithiation is facilitated by derivatizing the hydroxyl group to form a methoxyethyl ether or dimethylaminoethyl ether.2 O

X = OMe, NMe2 X

lithiation site (with s-BuLi)

The benzylic position of 2-arylaziridines is readily lithiated. N-Substituted trans-2,3diphenylaziridines afford diastereomers according to the solvent used (whether HMPA is present).3 More dramatic differences are observed in the case of aziridines bearing an oxazoline substituent at C-2.4 Ph s-BuLi THF

Ph

NR Li

Ph

NR Ph

Ph s-BuLi TMEDA hexane

O

NR Ph

Li

O N

N

n-BuLi

N Bn

Li

THF –98°

N Bn

O

O N

N

s-BuLi

N

Ph

TMEDA –98°

N Li

Ph

t-Butyllithium

91

Rearrangement. Ureas containing aryl and benzyl units on different nitrogen atoms undergo N -. C aryl shift, as a result of benzylic lithiation and addition to the distal aryl group.5 O O Ar

N

Ph N R

N

s-BuLi THF –78°

O

N R H2O

Ph

–

H

N

Ph N R

Ar

Li 1

Castanet, A.-S., Tilly, D., Veron, J.-B., Samanta, S.S., De, A., Ganguly, T., Mortier, J. T 64, 3331 (2008). 2 Wilkinson, J.A., Raiber, E.A., Ducki, S. TL 48, 6434 (2007). 3 Luisi, R., Capriati, V., Florio, S., Musio, B. OL 9, 1263 (2007). 4 Luisi, R., Capriati, V., DiCunto, P., Florio, S., Mansueto, R. OL 9, 3295 (2007). 5 Clayden, J., Dufour, J., Grainger, D.M., Helliwell, M. JACS 129, 7488 (2007).

t-Butyllithium. X/Li exchange. A synthetic approach to 4-hydroxycycloheptanones from g-(3iodopropyl)butyrolactones is proven successful via I/Li exchange and intramolecular acylation. At least in the example shown below, cyclization induced by SmI2 is not a viable alternative.1 O

OH

O

O

t-BuLi

I

O

THF

OTBS

TBSO

TBSO

OH

The unique quality of Br/Li exchange with t-BuLi enables the synthesis of an a-hydroxy(3-furanylmethyl)-2-butenolide, whereas many other coupling method fail.2 OH

OTIPS Br

t-BuLi

O

TIPSO

TIPSO O

Fu-CHO

Me3Si

OH

OTIPS O

O

O Me3Si

O

50%

A method for the preparation of ArBF3K from ArX calls for treatment with t-BuLi and subsequent reaction with (i-PrO)3B, and ﬁnally, with KHF2.3 Lithiation. A molecule featuring both a ﬂuoroarene and a bromoarene subunit gives rise to aryne and lithioarene moieties on the treatment with t-BuLi. If such reactive components are spatially interactable, intramolecular addition can occur.4

92

N-(t-Butyl)phenylsulﬁnimidoyl chloride

F

Br

Li

N

N

t-BuLi

O

O

THF –110°

O

O O O Li

N

Reduction. A rare showing of the reductive potential of t-BuLi is in its reaction with 1-bromo-1-dicyclohexylborylalkenes. Hydride transfer from t-BuLi to the boron atom triggers a debrominative rearrangement.5

Br

Br

Cy2BH;

H BCy2

Cy2B

–

t-BuLi

R

R

R

Et2Zn R' EtZn R'CHO

HO R

R

1

Ohtsuki, K., Matsuo, K., Yoshikawa, T., Moriya, C., Tomita-Yokotani, K., Shishido, K., Shindo, M. OL 10, 1247 (2008). 2 He, W., Huang, J., Sun, X., Frontier, A.J. JACS 130, 300 (2008). 3 Park, Y.H., Ahn, H.R., Canturk, B., Jeon, S.I., Lee, S., Kang, H., Molander, G.A., Ham, J. OL 10, 1215 (2008). 4 Sanz, R., Fernandez, Y., Castroriejo, M.P., Perez, A., Fananas, F.J. EJOC 62 (2007). 5 Salvi, L., Jeon, S.-J., Fisher, E.L., Carroll, P.J., Walsh, P.J. JACS 129, 16119 (2007).

N-(t-Butyl)phenylsulﬁnimidoyl chloride. Dehydrogenation. Direct introduction of a functional chain (e.g., malonic ester) to the b-position of a cycloalkanone involves treatment with LDA and the title reagent, and

N-(t-Butyl)phenylsulﬁnimidoyl chloride

93

followed by the nucleophile.1 Lactams are functionalized at the carbon a to the nitrogen atom, after deprotonation.2 O

O BuLi, HMPA;

NH

t-BuN

S

Ph

Cl CH2(COOR)2

NH COOR ROOC

Activation of the benzylic position of 3-benzylindoles is similarly accomplished.3 nucleophile Ar

Ar BuLi, THF

N H 1

t-BuN

S

Ph Cl

Matsuo, J., Kawai, H., Ishibashi, H. TL 48, 3155 (2007). Matsuo, J., Tanaki, Y., Ishibashi, H. TL 48, 3233 (2007). 3 Matsuo, J., Tanaki, Y., Ishibashi, H. T 64, 5262 (2008). 2

N

C Calcium bis(hexamethyldisilazide). Redox reaction. Aromatic aldehydes are converted into benzyl aroates on exposure, at room temperature, to the silylamides of alkali earth metals, including those of Ca, Sr, and Ba.1 1

Crimmin, M.R., Barrett, A.G.M., Hill, M.S., Procopiou, P.A. OL 9, 331 (2007).

Carbonyl(chloro)hydridobis(tricyclohexylphosphine)ruthenium. Disiloxanes. Vinyltriorganosilanes exchange the vinyl group for a triorganosilanol to form disiloxanes, when they are heated with the Ru complex in toluene.1 1

Marciniec, B., Pawluc, P., Hreczycho, G., Macina, A., Madalska, M. TL 49, 1310 (2008).

Carbonyl(chloro)hydridotris(triphenylphosphine)rhodium. Homoallylic and homopropargylic alcohols. Redox combination of primary alcohols and conjugated dienes1 or 1-alken-3-ynes2 takes place in the presence of the Rh complex, providing homoallylic alcohols and homopropargylic alcohols, respectively. In the reaction of the dienes allylmetal reagents are formed on hydrogen transfer from the alcohols. R

OH +

R

R'

OH +

R'

R

(Ph3P)3Ru(CO)ClH THF

OH R'

R

OH

(Ph3P)3Ru(CO)ClH DPPF THF 95°

R'

Enolization via long-range migration. An unsaturated ketone with a remote double bond uninterrupted by a quaternary carbon or heteroatom is capable of forming a Ru-enolate by heating with the title complex in benzene. Such an enolate can be trapped by aldehydes and the resulting ruthenated aldols afford 1,3-diketones through eliminated of [Ru]-H.3

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 95

96

Carbonyldihydridotris(triphenylphosphine)ruthenium

O O

(Ph3P)3Ru(CO)ClH PhH RCHO

O R

1

Shibahara, F., Bower, J.F., Krische, M.J. JACS 130, 6338 (2008). Patman, R.L., Williams, V.M., Bower, J.F., Krische, M.J. ACIE 47, 5220 (2008). 3 Fukuyama, T., Doi, T., Minamino, S., Omura, S., Ryu, I. ACIE 46, 5559 (2007). 2

Carbonyldihydridotris(triphenylphosphine)ruthenium. Oxidation. The Ru complex, with Xantphos, 2 equivalents of water and crotonitrile (as hydrogen acceptor), can be used to oxidize primary alcohols. In the presence of MeOH the generation of methyl esters is realized.1 Internal redox reaction of 1,4-butanediol under basic conditions (t-BuOK) leads to the formation of g-butyrolactone.2 Aldoximes are oxidized to primary amides, only that reaction conditions are somewhat different: additive being TsOH . H2O besides a phosphine ligand.3 Coupling reactions. The Ru complex catalyzes replacement of the amino group of o-aminoaryl ketones with the carbon residue of an organoboronic ester.4 Direct activation of a CZH bond ortho to the carbonyl group is also possible.5 'R

'R +

O

B

(Ph3P)3Ru(CO)H2

O

O R

O R

Furans and pyrroles. 2-Alkyne-1,4-diols undergo isomerization to 1,4-diones and subsequent dehydration to afford furans,6 on heating with the Ru complex, Xantphos, and PhCOOH in toluene at 808. The intermediates are of course convertible to pyrroles.7 1

Owston, N.A., Parker, A.J., Williams, J.M.J. CC 624 (2008). Maytum, H.C., Tavassoli, B., Williams, J.M.J. OL 9, 4387 (2007). 3 Owston, N.A., Parker, A.J., Williams, J.M.J. OL 9, 3599 (2007). 4 Ueno, S., Chatani, N., Kakiuchi, F. JACS 129, 6098 (2007). 5 Ueno, S., Chatani, N., Kakiuchi, F. JOC 72, 3600 (2007). 6 Pridmore, S.J., Slatford, P.A., Williams, J.M.J. TL 48, 5111 (2007). 7 Pridmore, S.J., Slatford, P.A., Daniel, A., Wittlesey, M.K., Williams, J.M.J. TL 48, 5115 (2007). 2

Cerium(IV) ammonium nitrate, CAN. Oxidations. Tertiary cyclopropanols undergo oxidative ring opening on exposure to CAN, an added salt provides anion to functionalize the emerging ethyl terminus.1

Cerium(IV) ammonium nitrate, CAN

OH R

O

CAN MX

97

X

R

X = Br, I, N3, SCN, . . .

CAN oxidizes the OH group of glycols and 1,2-amino alcohols to initiate CC bond cleavage. The alcohol unit from a glycol monoether is released.2 Analogously, oxidative degradation of proline and prolinol derivatives gives 2-hydroxypyrrolidines.2 N-Arylpyroglutamic acids are further oxidized to afford succinimides (CAN –NaBrO3 protocol).3 Selective conversion of a methylenedioxyarene to an o-quinone is a crucial step in a synthesis of phleblarubrone.4 On the other hand, veratrole derivatives are cleaved to afford hexadienoic esters.5

O

O

O

O

CAN

Ph

Ph O

O

MeCN H2O

Ph

Ph

0°

100%

O

O

phleblarubrone OMe MeO O

O

COOMe

CAN MeCN H 2O

O

O

COOMe 90%

Formation of a new ring system by involving a released N-methoxymethylamine chain during arene oxidation is a surprising reward, despite the low yield.6 OMe

N

O

O CAN

N MeO

N OMe

MeCN H2O

N MeO

O 31%

In the introduction of a sidechain to C-2 of the quinoline nucleus via 1,2-addition (extended Reissert reaction) to form an adduct with a N-( p-methoxybenzyl) group, the rearomatization step can be initiated by oxidative CZN bond cleavage with CAN.7

98

Cerium(IV) ammonium nitrate, CAN

N

CF3

CAN

H

MeOH

CF3

N

OMe

The CZN bond of N-arylhydrazides (with electron-deﬁcient Ar) is reductively cleaved after oxidative activation by CAN, where MeOH serves as hydride source.8 Oxidative coupling. Dialkenylsiloxanes are decomposed into 1,4-dicarbonyl compounds by oxidation with CAN.9 R O

Si

O

O

R

CAN aq. NaHCO3

O

MeCN 0°

N-Benzyl-3-azabicyclo[3.1.0]hexan-1-ols, which are readily available from a Kulinkovich reaction, are converted by CAN into benzannulated 1-azabicyclo[3.3.1]nonan-3-ones.10 This oxidation pathway differs from that mediated by FeCl3. Ph N

R CAN

H

Ph N

R

FeCl3;

N

R

NaOAc

O

OH

O

Substitution. Acetates of Baylis–Hillman adducts of acrylic esters and ArCHO are transformed into amines via an SN20 pathway, which is catalyzed by CAN.11 Addition reactions. CAN serves as a catalyst for the conjugate addition of thiols and selenols to enones under solvent-free conditions.12 Glycals are transformed into glycosides containing a nitromethyl group at C-2.13 RO RO

OR O

CAN MeOH MeNO2 KOH, 0°

RO RO

OR O OMe NO2

It appears that CAN acts as a Lewis acid to catalyze addition of enol ethers to N-arylalimines, which is followed by an intramolecular Friedel –Crafts reaction to furnish 4-alkoxy-1,2,3,4-tetrahydroquinolines.14

Cesium ﬂuoride

99

a-Nitrocinnamate esters. Cinnamate esters are further functionalized by nitrating agent generated in situ from NaNO2 and CAN.15 gem-Bishydroperoxides. Various carbonyl compounds (ArCHO and ketones) are converted into the oxygen-rich compounds by aqueous H2O2 in the presence of catalytic CAN at room temperature.16 1

Jiao, J., Nguyen, L.X., Patterson, D.R., Flowers II, R.A., OL 9, 1323 (2007). Fujioka, H., Hirose, H., Ohba, Y., Murai, K., Nakahara, K., Kita, Y. T 63, 625 (2007). 3 Barman, G., Roy, M., Ray, J.K. TL 49, 1405 (2008). 4 Hayakawa, I., Watanabe, H., Kigoshi, H. T 64, 5873 (2008). 5 Marrero, J.G., San Andres, L., Luis, J.G. SL 1127 (2007). 6 Sperry, J., McErlean, C.S.P., Slawin, A.M.Z., Moody, C.J. TL 48, 231 (2007). 7 Loska, R., Majcher, M., Makosza, M. JOC 72, 5574 (2007). 8 Stefane, B., Polanc, S. SL 1279 (2008). 9 Clift, M.D., Taylor, C.N., Thomson, R.J. OL 9, 4667 (2007). 10 Jida, M., Guillot, R., Ollivier, J. TL 48, 8765 (2007). 11 Paira, M., Mandal, S.K., Ray, S.C. TL 49, 2432 (2008). 12 Chu, C.-M., Gao, S., Sastry, M.N.V., Kuo, C.-W., Lu, C., Liu, J.-T., Yao, C.-F. T 63, 1863 (2007). 13 Elamparuthi, E., Linker, T. OL 10, 1361 (2008). 14 Sridharan, V., Avendano, C., Menedez, J.C. SL 1079 (2007). 15 Buevich, A.V., Wu, Y., Chan, T.-M., Stamford, A. TL 49, 2132 (2008). 16 Das, B., Krishnaiah, M., Veeranjaneyulu, B., Ravikanth, B. TL 48, 6286 (2007). 2

Cerium(III) chloride. Reduction. Alkyl azides are reduced to primary amines with CeCl3 . 7H2O – NaI in hot MeCN.1 1

Bartoli, G., Di Antonio, G., Giovannini, R., Giuli, S., Lanari, S., Paoletti, M., Marcantoni, E. JOC 73, 1919 (2008).

Cesium ﬂuoride. Substitution. CsF is an excellent ﬂuoride ion source for converting alkyl mesylates to RF, especially in the presence of the imidazolium mesylate 1.1 The effect, due to hydrogen bonding to the tertiary alcohol to render the ﬂuoride ion more nucleophilic but less basic (so as to minimize elinination [H-OMs]), is also manifested in a polymer-linked 1,2 and a combination of t-AmOH and a polymer-supported ionic liquid.3 –

MsO R N+ N

OH

(1) Transacylation. Only catalytic amounts of CsF are needed for protection of hydroxyindoles as N-Boc derivatives without affecting hydroxyl group4 and transesteriﬁcation of b-keto esters.5

100

Cesium ﬂuoride

Aryne generation. The desilylative route (e.g., by CsF) is the most expedient method for generation of arynes. 1,2-Functionalization of arenes from 2-trimethylsilylaryl triﬂates is readily achieved as long as noninterfering co-reactants are used. Thus trapping by organoazides leads to benzotriazoles,6 by phenyliodonium diacylmethylides leads to 3-acylbenzofurans,7 and reaction in the presence of benzoic esters o-substituted with XH groups (X ¼ O, S, NH) gives xanthones, thioxanthones, and acridones.8 [Direct diazotization of anthranilic acid affords acridone.9] O

R

I

O

R

CsF MeCN

R'

R' O

O

O COOMe

TfO CsF

+ XH

Me3Si

X

An amide anion simultaneously released by desilylation of Me3SiNR2 is able to add to the aryne and then trapped with an aldehyde. Deployment of this strategy realizes a synthesis of o-aminobenzyl alcohols.10 R

NR2 SiMe3

+

NR2

CsF PhCOOH

R'CHO

R

R' OH

1,2-Bisphenylselenoarenes are readily prepared on generating the arynes in the presence of PhSeSePh.11 An electrophile role is played by an aryne also in the arylation (at the a-position) of b-amino-a,b-unsaturated ketones and esters.12 Most interesting is the coupling reactions at two adjacent position of an aromatic ring, for example, on basis of Pd-catalyzed reactions. Examples include the one-pot synthesis of 2-(1-alkenyl)biphenyls13 and o-allylarylalkynes.14 Ar

Ar-I

OTf

CsF

+

Pd(OAc)2 – o -Tol3P

SiMe3

R

OTf

MeCN 45°

R

Cl CsF – CuI

+ SiMe3 R

DPPE K2CO3

R

Chiral auxiliaries and catalysts

101

With co-presence of ArI, alkynes, TlOAc and (dba)2Pd in the reaction pot in which the aryne is generated, multicomponent coupling directed toward phenanthrenes is realized.15 1

Shinde, S.S., Lee, B.S., Chi, D.Y. OL 10, 733 (2008). Shinde, S.S., Lee, B.S., Chi, D.Y. TL 49, 42453 (2008). 3 Kim, D.W., Jeong, H.-J., Lim, S.T., Sohn, M.-H., Chi, D.Y. T 64, 4209 (2008). 4 Inahashi, N., Matsumiya, A., Sato, T. SL 294 (2008). 5 Inahashi, N., Fujiwara, T., Sato, T. SL 605 (2008). 6 Shi, F., Waldo, J.P., Chen, Y., Larock, R.C. OL 10, 2409 (2008). 7 Huang, X.-C., Liu, Y.-L., Liang, Y., Pi, S.-F., Wang, F., Li, J.-H. OL 10, 1525 (2008). 8 Zhao, J., Larock, R.C. JOC 72, 583 (2007). 9 Ho, T.-L., Jou, D.-G. JCCS(T) 48, 81 (2001). 10 Yoshida, H., Morishita, T., Fukushima, H., Ohshita, J., Kunai, A. OL 9, 3367 (2007). 11 Toledo, F.T., Marques, H., Comasseto, J.V., Raminelli, C. TL 48, 8125 (2007). 12 Ramtohul, Y.K., Chartrand, A. OL 9, 1029 (2007). 13 Henderson, J.L., Edwards, A.S., Greaney, M.F. OL 9, 5589 (2007). 14 Xie, C., Liu, L., Zhang, Y., Xu, P. OL 10, 2393 (2008). 15 Liu, Z., Larork, R.C. ACIE 46, 2535 (2007). 2

Chiral auxiliaries and catalysts. Kinetic resolution. Various situations that dynamic kinetic resolution applies are reviewed.1 Resolution by enantioselective benzoylation of 2-benzoylamino-1,3-propanediols is accomplished in the presence of the CuCl2-complex of ligand 1A.2 Selective esteriﬁcation catalyzed by 2 is for dynamical kinetic resolution of hemiaminals and aminals,3 whereas tosylation of a-hydroxycarboxamides proceeds well under the inﬂuence of Cu(OTf)2 – ent-1B.4 R"

R"

O R'

O N

N

R

(1A) (1B) (1C) (1D) (1E) N

R'

HO

R

HO

NHBz

R R = R' = Ph, R" = Me

CuCl2

Et3N

(1A)

BzCl

R = Ph, R' = H, R" = Me R = Ph, R' = H, R" = Bn R = t-Bu, R' = R" = H R = t-Bu, R' = H, R" = Me O

S N

N

(2)

S

BzO

R *

HO

NHBz

102

Chiral auxiliaries and catalysts

The iridium complex 3 has found use in kinetic resolution of secondary benzylic alcohols (indanol, a-tetralol, . . .) by its mediation of enantioselective aerobic oxidation.5,6

Ms N Ir N H

Ph Ph

(3) TADDOL spiroannulated to a cyclohexane proves useful for deracemization of a-benzyloxy ketones.7 Members belonging to one enantiomeric series of 5-substituted 2-cyclohexenones remain for being more resistant to attack by R2Zn in the presence of a Cu(I) salt and the peptide derivative 4.8 By rapid reduction of one enantiomeric series of benzylic hydroperoxides, [2.2]paracyclophane-based diphosphine 5 kinetically resolves those active compounds.9

Boc

H N

O N H Ph

PAr2

N O

PPh2

PAr2

(5)

(4)

Oxidative ring cleavage in the presence of 6 is the basis of a kinetic resolution of N-acyloxazolidines.10

O O

N OH

Ph

NOH O

OH N O

Ph

(6) Desymmetrization. Selective reaction of meso-compounds to provide desired chiral products is highly valued. By furnishing the t-Bu-PHOX 7 to form a proper Rh(I)-catalyst,

Chiral auxiliaries and catalysts

103

reaction of organozinc reagents with cis-2,4-dimethylglutaric anhydride delivers chiral d-keto acids.11

O N

PPh2

(7)

Aminolysis of meso-epoxides is facilitated by Sc(OTf)3. In the presence of bipyridyldiol 8 chiral products are obtained.12 meso-N-Acylaziridines react with Me3SiN3 to provide b-azido amines, and a chiral Bronsted acid (e.g., 9) renders the ring opening asymmetrical.13

Ph Ph

N

N O

OH

HO

O

(8)

P

O OH

(9)

Reductive conversion of meso-cyclic imides to v-hydroxyalkanamides is enantioselective when rendered by the hydrogenation catalyst 10.14

Ph2P Ru Cl HN

(10) meso-1,2-Diols are desymmetrized by benzoylation in the presence of 11 15 and tosylation in the presence of ent-1B.16 By virtue of diastereoselective selection enantioselective N-benzoylation of a-amino esters with the chiral reagent 12 has been achieved.17

104

Chiral auxiliaries and catalysts

Ph Ph

Ph O O

S

N

N N

N

Ph

N

Ts

N

N Bn

polymer

H OAc O

Ph

(12)

(11) A synthesis of (-)-lobeline from the cis-diol precursor has been completed. Selective esteriﬁcation followed by oxoidation and saponiﬁcation are involved, the critical esteriﬁcation step is mediated by 13.18

OH S N

H

Ph

N

H

OH

N Me

Ph

Ph

(13) OH Ph

H

H N Me

O Ph

(-)-lobeline

Finding effective chiral ligands is the key to formation of semistabilized chiral lithioalkanes. Success has been demonstrated from a combination of BuLi and 1C for benzyl triﬂuoromethyl sulfones19 and that of t-BuLi and the sparteine surrogate 14 for N-Boc pyrrolidine.20

H N N

t-BuLi/(14);

NBoc

Br

NBoc

H

(14) Chiral lithioamide bases of the a-phenthylamine type are known to perform asymmetric lithiation of meso-ketones. A ﬂuorous analogue 15 (as LiCl complex) is now available for the purpose.21

Chiral auxiliaries and catalysts

105

C10F21 .LiCl

N Li

Ph

(15) 1

Pellissier, H. T 64, 1563 (2008). Hong, M.S., Kim, T.W., Jung, B., Kang, S.H. CEJ 14, 3290 (2008). 3 Yamada, S., Yamashita, K. TL 49, 32 (2008). 4 Onomura, O., Mitsuda, M., Nguyen, M.T.T., Demizu, Y. TL 48, 9080 (2007). 5 Arita, S., Koike, T., Kayaki, Y., Ikariya, T. ACIE 47, 2447 (2008). 6 Wills, M. ACIE 47, 4264 (2008). 7 Matsumoto, K., Otsuka, K., Okamoto, T., Mogi, H. SL 729 (2007). 8 Soeta, T., Selim, K., Kuriyama, M., Tomioka, K. T 63, 6573 (2007). 9 Driver, T.G., Harris, J.R., Woerpel, K.A. JACS 129, 3836 (2007). 10 Nechab, M., Kumar, D.N., Philouze, C., Einhorn, C., Einhorn, J. ACIE 46, 3080 (2007). 11 Cook, M.J., Rovis, T. JACS 129, 9302 (2007). 12 Mai, E., Schneider, C. CEJ 13, 2729 (2007). 13 Rowland, E.B., Rowland, G.B., Rivera-Otero, E., Antilla, J.C. JACS 129, 12084 (2007). 14 Ito, M., Sakaguchi, A., Kobayashi, C., Ikariya, T. JACS 129, 290 (2007). 15 Arai, T., Mizukami, T., Yanagisawa, A. OL 9, 1145 (2007). 16 Demizu, Y., Matsumoto, K., Onomura, O., Matsumura, Y. TL 48, 7605 (2007). 17 Karnik, A.V., Kamath, S.S. JOC 72, 7435 (2007). 18 Birman, V.B., Jiang, H., Li, X. OL 9, 3237 (2007). 19 Nakamura, S., Hirata, N., Kita, T., Yamada, R., Nakane, D., Shibata, N., Toru, T. ACIE 46, 7648 (2007). 20 Stead, D., O’Brien, P., Sanderson, A. OL 10, 1409 (2008). 21 Matsubara, H., Maeda, L., Sugiyama, H., Ryu, I. S 2901 (2007). 2

Electrophilic substitution. Enantioselective ﬂuorination by (PhSO2)2NF is carried out with the aid of a Pd complex of 16A.1

R

O

R

O

PAr2

R

O

PAr2

R

O

(16A) R = H, Ar = (16B) R = Me, Ar = Ph (16C) R = F, Ar = Ph

OMe

106

Chiral auxiliaries and catalysts

Recent efforts pertaining to direct attachment of chiral sidechain to a heteroarene show that enantioselective Pictet – Spengler reaction is achievable in the presence of a multifunctional thiourea.2 An interesting observation is that annulation of pyrroles by this method (with 17) can give different isomers from CC bond formation at an a- or b-carbon.3

AcCl/(17) R' = H

O

S C5H11

N O

N H

N H

R N

N N H

N

(17)

R

O

N HO R'

Ph

O

N R' = TIPS

R

Me2SiCl/(17)

N TIPS

For asymmetric propargylation of furans the Ru complex 18 in which chirality instruction is furnished by a benzylic sulﬁde group is used.4

Cl Ru S Ph

Ph

2

Ph

(18) A rather general method for homologating secondary alkyl halides (e.g., bromides) is by the Ni-catalyzed reaction with organoboranes. Asymmetric induction by the C2-symmetric diamine 19 is now realized.5

F3C

CF3

NH HN

(19)

Chiral auxiliaries and catalysts

107

Potassium alkenyltriﬂuoroborates are activated by CAN for a-alkenylation of aldehydes which become chiral nucleophiles on condensation with 20A.6 O NMe N H

Ar

(20A) Ar = Ph (20B) Ar = N-Bn-3-indolyl Alkylation of tin enolates in the presence of a chiral (salen)-Cr complex shows moderate ee, due to rate differences for the reaction of two geometrically isomeric enol stannyl ethers.7

OSnBu3

O fast

O N

Cl

Cr N

SnBu3

O O

O

OSnBu3 slow

N,N0 -Disubstituted thioureas exempliﬁed by 21 help ionize the chlorine atom of a 1-chloroisochroman to generate oxocarbenium species that can be trapped in an enantioselective sense.8 OSiMe3

CF3 O +

S N O F

N H

N H

CF3

R

OR" R'

Cl

(21)

(21) O R' R

COOR"

108

Chiral auxiliaries and catalysts

Alkylation of aldehydes with enol silyl ethers is accomplished on oxidation of the latter species with CAN. By forming chiral enamines from the aldehydes and the imidazolidinone 20 in situ the reaction furnishes optically active products.9 The utility of the Pd-complex of 22 is further extended to synthesis of chiral 2-alkoxy-4pentenals from vic-alkoxyalkenyl allyl carbonates.10

O

O NH HN PPh2 Ph2P

(22) 1

Suzuki, T., Goto, T., Hamashima, Y., Sodoka, M. JOC 72, 246 (2007). Raheem, I.T., Thiara, P.S., Peterson, E.A., Jacobsen, E.N. JACS 129, 13404 (2007). 3 Raheem, I.T., Thiara, P.S., Jacobsen, E.N. OL 10, 1577 (2008). 4 Matsuzawa, H., Migake, Y., Nishibayashi, Y. ACIE 46, 6488 (2007). 5 Saito, B., Fu, G.C. JACS 130, 6694 (2008). 6 Kim, H., MacMillan, D.W.C. JACS 130, 398 (2008). 7 Doyle, A.G., Jacobsen, E.N. ACIE 46, 3701 (2007). 8 Reisman, S.E., Doyle, A.G., Jacobsen, E.N. JACS 130, 7198 (2008). 9 Jang, H.-Y., Hong, J.-B., MacMillan, D.W.C. JACS 129, 7004 (2007). 10 Trost, B.M., Xu, J., Reichle, M. JACS 129, 282 (2007). 2

Allylic substitutions. Allylic substitution is still largely dependent on Pd-catalysis because of its efﬁciency and mechanistic understanding. Many new chiral ligands are tested for their asymmetric induction, including as diverse as the ferrocenyl S,P-ligands 23 1/24 2 and 25.3

SCy Fe MeN PPh2

SEt Fe

N

PPh2 N

(23)

PhY NHCOAr Y = S, Se, Te

(24)

(25)

Ligands with coordination sites distributed over two different cyclopentadienyl units of the ferrocenyl nucleus are represented by 26, for use in the Pd-catalyzed allylic substitution.4

Chiral auxiliaries and catalysts

109

O Fe

N NEt 2 P O (S)-BINOL

(26) Molybdenum catalysts usually complement the Pd based species in terms of regiochemical consequences. A particularly striking result obtained in the cinnamylation of 3-substituted oxindoles5 indicates that, by example of difference in a 2-thienyl and a 3-methyl-2-thienyl substituents, variation in substrate structure can be signiﬁcant and hence exploitable.

R S O

+

N

(27)

Mo(C7H8)(CO)3

N Me

NH HN N

Ph

O

O

Ph

S

(27)

O

O N Me

O O

Substitution of allylic phosphates by alkenyldiisobutylalanes proceeds via the SN20 route, CuCl2 in combination with a dinuclear silver-carbene complex (28) are responsible for excellent asymmetric induction.6 Ph O O S N

Ph NMes

O Ag O

Ag

N S O O Ph

NMes Ph

(28) Mixed carbonates of unsymmetrical dialkenyl carbinols undergo ipso-substitution to afford chiral aryl ethers, with high degrees of regioselectivity and enantioselectivity when catalyzed by a Pd(0)-complex of 29.7

110

Chiral auxiliaries and catalysts

O

O NH HN PPh2 Ph2P

(29) Certain P-chiral phosphorodiamidite ligands (e.g., 30A, 30B) complex with iridium(I) to form catalysts for promoting reaction of cinnamyl methyl carbonate with ArOH to form chiral aryl a-vinylbenzyl ethers.8

OPh (30A)

O Ar N P Ar'

Ph

H Ph

N O

[(cod)IrCl]2

OCOOMe

Et3N

+ PhOH

OPh

THF (30B)

Ph

(30A) Ar = Ph, Ar' = 2,6-Me2C6H3 (30B) Ar = 2,6-Me2C6H3, Ar' = Ph

Branched allylic ethers are also obtained from a reaction of 1-chloro-2-alkenes with alcohols. A Ru catalyst (31) shows satisfactory activity.9

O O MeCN MeCN

Ru P Ph

Ph

(31) Synthesis of chiral allylic amines by substitution reaction has many choices of protocol, in terms of metal complexes and ligands. Pd catalysts having pairing with a C2-symmetric ruthenocene (32) are quite novel10 among other more conventional P,N-ligands that include 33 11 and 34.12

Chiral auxiliaries and catalysts

111

Ph N H

COOMe PPh2

P O N

P

O

N

Ru PPh2 COOMe

H

O

O

H O P

N H N

(32)

Ph

(33)

(34)

Cyclic diaminophosphine oxide 35 ligating to Pd is useful for substitution of allylic carbonates.13 To access diamines from 2-vinylaziridines the catalyst system constituting 29 meets established standards.14

MeO MeO N

MeO MeO

H P O N Bn

OCOOMe X

NRR' (35)

X

RR'NH

NH

(35)

It is possible to prepare allylic boronates by a Cu-catalyzed reaction of allylic carbonates with bis(pinacolato)diboron. A chiral version of the reaction uses a QuinoxP ligand (36).15

P N

(36)

P

R O P N Ph O

(37)

A chiral Ir(I) catalyst derived from the amino-(2,20 -biphenoxy)phosphine 37 promotes the synthesis of optically active 3-amino-1-alkenes from 2-alkenols, which are activated by (Eto)5Nb.16 1-Vinyl-1,2,3,4-tetrahydroisoquinolines are obtained in good yields in the Pd-catalyzed process. Enantioselectivity is induced by the atropisomeric 38.17

112

Chiral auxiliaries and catalysts

R NHR O

X

CHCH2OCOOR'

P N O R

(38A) R = Ph (38B) R = t-Bu

(dba)3Pd2 (38A)/CH2Cl2

X

* NR

3-Butenoic esters bearing a chiral quaternary a-carbon center are prepared by Grignard reaction of a-substituted g-chlorocrotonic esters in the presence of (4R, 5R)-diphenyl-1,3dimesitylimidazolylidene.18 1

Lam, F.L., Au-Yeung, T.T.-L., Kwong, F.Y., Zhou, Z., Wong, K.Y., Chan, A.S.C. ACIE 47, 1280 (2008). 2 Cheung, H.Y., Yu, W.-Y., Lam, F.L., Au-Yeung, T.T.-L., Zhou, Z., Chan, T.H., Chan, A.S.C. OL 9, 4295 (2007). 3 Vargas, F., Sehnem, J.A., Galetto, F.Z., Braga, A. T 64, 392 (2008). 4 Zhang, K., Peng, Q., Hou, X.-L., Wu, Y.-D. ACIE 47, 1741 (2008). 5 Trost, B.M., Zhang, Y. JACS 129, 14548 (2007). 6 Lee, Y., Akiyama, K., Gillingham, D.G., Brown, M.K., Hoveyda, A.H. JACS 130, 446 (2008). 7 Trost, B.M., Brennan, M.K. OL 9, 3691 (2007). 8 Kimura, M., Uozumi, Y. JOC 72, 707 (2007). 9 Onitsuka, K., Okuda, H., Sasai, H. ACIE 47, 1454 (2008). 10 Liu, D., Xie, F., Zhang, W. JOC 72, 6992 (2007). 11 Birkholz, M.-N., Dubrovina, N.V., Shuklov, I.A., Holz, J., Paciello, R., Waloch, C., Breit, B., Bo¨rner, A. TA 18, 2055 (2007). 12 Gavrilov, K.N., Zheglov, S.V., Vologzhanin, P.A., Maksimova, M.G., Safronov, A.S., Lyubimov, S.E., Davankov, V.A., Scha¨ffner, B., Bo¨rner. TL 49, 3120 (2008). 13 Nemoto, T., Fukuyama, T., Yamamoto, E., Tamura, S., Fukuda, T., Matsumoto, T., Akimoto, Y., Hamada, Y. OL 9, 927 (2007). 14 Trost, B.M., Fandrick, D.R., Brodmann, T., Stiles, D.T. ACIE 46, 6123 (2007). 15 Ito, H., Ito, S., Sasaki, Y., Matsuura, K., Sawamura, M. JACS 129, 14856 (2007). 16 Yamashita, Y., Gopalarathnam, A., Hartwig, J.F. JACS 129, 7508 (2007). 17 Shi, C., Ojima, I. T 63, 8563 (2007). 18 Lee, Y., Hoveyda, A.H. JACS 128, 15604 (2006).

Addition to CvO bond. Hydroxyalkylation of benzyl triﬂuoromethyl sulfones via lithiation can lead to chiral alcohols by adding the BOX ligand 1C to the reaction medium.1 Addition of organozinc reagents to aldehydes still occupy the attention of many methodology developers, although, unfortunately, most of the works have not gone beyond certain model reactions of Et2Zn and ArCHO. The addition is found to be enantioselective using a Ti complex of the ﬂuorous TADDOL 39.2 Since many diamines and amino alcohols have high afﬁnity to zinc metal it is not surprising that chiral ligands with such motifs emerge unabated. Akin in partial structure are 40,3 41,4 42,5 and 43.6

Chiral auxiliaries and catalysts

R O O R

R OH

Ph

113

Ph OH N

OH R

(39) R = C8F17

(40) OH Ph

N

Fe HO Ph

Fe

N

Fe

N H

HO

Ph

(42)

(41)

Ph Ph

(43)

It should be noted that stoichiometric quantitites of R2Zn transfer the R group to aldehydes, catalytic amounts of R2Zn (and correspondingly the chiral ligands) serve as catalysts (as shown with 41) in the addition involving organoboronic acids.7 The SAc group in 44 in enhancing asymmetric induction is ascribed to its strong afﬁnity toward Zn such that the coordination sphere is more rigid. The 2-exo-morpholinobornane10-thiol 45 perhaps cherishes the same advantages (in reactions involving alkenylzinc reagents).8

Ph R

S O NR'2

N SH

(44)

O

(45)

Ligand 46 has a secondary amino group,9 whereas 47 performs better because it is a tridentate ligand.10

Ph Ph

NH OH

(46)

a-Np

OH HO N N Me

(47)

N

a-Np

HN P O

(48)

Modiﬁed diamines as ligands, including monophosphonamides (e.g., 48 11) and carboxamides (e.g., 49 12), have been scrutinized. In the use of 49 for forming complexes with the

114

Chiral auxiliaries and catalysts

Ni(II) ion as catalysts rather surprising and desirable results emerge. Chirality switch is observed from reactions mediated by a complex bearing one to that bearing two such ligands. OH Ni(49)

Ph

NHBn

O Ph

NH2

Et2Zn + PhCHO

OH

Ni(49)2

(49)

Ph

Chiral phthalides are synthesized from an o-iodobenzoic ester that forms a zinc compound. With a P-chiral diphosphinocobalt complex 50 present the addition to aldehydes follows an asymmetric course.13 MeO

OMe P

Ph

I

Co

P I

Ph

(50) Methylmagnesium bromide modiﬁed by ZnCl2 reacts with aldehydes in the presence of the Ti alkoxide derived from 51. It leads to chiral 2-alkanols.14 A Ti(IV) complex of the C2-symmetric isophthalamide 52 15 and a diastereomer of 42 16 catalyze the addition of alkynylzinc reagents to aldehydes, whereas the polymer-linked hydroxy-imine 53 alone is used for the same purpose.17

O C7F15

OH OH

C7F15

(51) Ph

OH N O

(53)

NH

HN

OH

HO

(52)

Ph Ph

Ph

O Ph

Chiral auxiliaries and catalysts

115

Allylic alcohols are synthesized from the reaction of aldehydes with alkenyl(ethyl)zincs that are complexed to (S)-2-diphenylhydroxymethyl-N-tritylaziridine.18 A piece of signiﬁcant information concerning the organozinc addition is that mixed aggregates from achiral and chiral catalysts are formed and such dimers are responsible for enantiomeric reversal.19 Another ﬁnding pertains to asymmetric ampliﬁcation such that great enantiomeric enrichment of certain ligands by cooling, keeping in solution ligands of good quality. To carry out Ti-catalyzed diorganozinc addition to aldehydes in the presence of (1S,2S)-bis(triﬂylamino)cyclohexane, cooling a toluene solution of the ligand to –788 achieves the effect.20 Asymmetric addition of allylmetals to carbonyl compounds is also a well-represented reaction type. Several N-oxides (54 21, 55A 22) are found to be effective catalysts for group transfer from allyltrichlorosilane and allylstannanes.

Ph

+ –

O

Ph

N

+

NHCHO

(54)

N

O R

NH

O–

+

N –

O

O HN

R

(55A) R = c-C5H9 (55B) R = 2,6-i-Pr2C6H3 A Cr(III) complex of the binaphthyl that is 2,20 -disubstituted by a 7-t-butyl-8-hydroxyquinol-2-yl group (56) is the source of chirality in the allenyl carbinols produced from reaction of propargylic bromides with aldehydes.23

N HO N

OH

(56) Homoallylic metallic species are generated from dienes in the presence of ent-57B and diastereoselective reaction with aldehydes has been observed.24 a-Keto esters are attacked by ArB(OH)2 under catalysis by [(C2H4)2RhCl]2 and chiral tertiary benzylic alcohols are obtained when the spirodiindanyl phosphite 57A is added to the reaction media.25

116

Chiral auxiliaries and catalysts

R

R

+

Ph O O

Et2Zn

P O

Ni(acac)2

ArCHO

(57A)/PhMe

OH

(57A) R = H

Ar

Ph R

(57B) R = OMe

(anti:syn >99 : 1)

Addition of cyanide ion to the carbonyl group is sterically directed by a thiourea 58, a cooperative catalyst capable of simultaneous hydrogen bonding with the oxygen atom of the acceptor molecule and guiding the cyanide ion by the protonated tertiary amine.26

(58) H O N H

S N H

N N H O

H N C

Titanium chelates of semi-salen 59 27 and salen 60 28 are used in asymmetric synthesis of a-cyanoalkyl ethyl carbonates from aldehydes and ethyl cyanoformate. By changing the metal atom to aluminum for complexing 60 a catalyst for elaborating a-acetoxy amides (Passerini reaction) is obtained (but enantioselectivity varies).29

N OH

(59) 1

OH

N

N

OH HO

(60)

Nakamura, S., Hirata, N., Yamada, R., Kita, T., Shibata, N., Toru, T. CEJ 14, 5519 (2008). Sokeirik, Y.S., Mori, H., Omote, M., Sato, K., Tarui, A., Kumadaki, I., Ando, A. OL 9, 1927 (2007). 3 Zhong, J., Guo, H., Wang, M., Yin, M., Wang, M. TA 18, 734 (2007). 4 Wang, M.-C., Zhang, Q.-J., Zhao, W.-X., Wang, X.-D., Ding, X., Jing, T.-T., Song, M.-P. JOC 73, 168 (2008). 5 ¨ . TA 18, 1013 (2007). Bulut, A., Aslan, A., Izgu¨, E.C., Dogan, O 2

Chiral auxiliaries and catalysts

117

6

Wang, M.-C., Wang, X.-D., Ding, X., Liu, Z.-K. T 64, 2559 (2008). Jin, M.-J., Sarkar, S.M., Lee, D.-H., Qiu, H. OL 10, 1235 (2008). 8 Wu, H.-L., Wu, P.-Y., Uang, B.-J. JOC 72, 5935 (2007). 9 Szatmari, I., Sillanpa¨a¨, R., Fu¨lo¨p, F. TA 19, 612 (2008). 10 Parrott III, R.W., Dore, D.D., Chandrashekar, S.P., Bentley, J.T., Morgan, B.S., Hitchcock, S.R. TA 19, 607 (2008). 11 Hatano, M., Miyamoto, T., Ishihara, K. OL 9, 4535 (2007). 12 Burguete, M.I., Collado, M., Escorihuela, J., Luis, S.V. ACIE 46, 9002 (2007). 13 Chang, H.-T., Jeganmohan, M., Cheng, C.-H. CEJ 13, 4356 (2007). 14 Omote, M., Tanaka, N., Tarui, A., Sato, K., Kumadaki, I., Ando, A. TL 48, 2989 (2007). 15 Hui, X.-P., Yin, C., Chen, Z.-C., Huang, L.-N., Xu, P.-F., Fan, G.-F. T 64, 2553 (2008). 16 Koyuncu, H., Dogan, O. OL 9, 3477 (2007). 17 Chen, C., Hong, L., Zhang, B., Wang, R. TA 19, 191 (2008). 18 Braga, A.L., Paixao, M.W., Westermann, B., Schneider, P.H., Wessjohann, L.A. SL 917 (2007). 19 Lutz, F., Igarashi, T., Kinoshita, T., Asahina, M., Tsukiyama, K., Kawasaki, T., Soai, K. JACS 130, 2956 (2008). 20 Satyanarayana, T., Ferber, B., Kagan, H.B. OL 9, 251 (2007). 21 Simonini, V., Benaglia, M., Pignataro, L., Guizzetti, S., Celentano, G. SL 1061 (2008). 22 Zheng, K., Qin, B., Liu, X., Feng, X. JOC 72, 8478 (2007). 23 Xia, G., Yamamoto, H. JACS 129, 496 (2007). 24 Yang, Y., Zhu, S.-F., Duan, H.-F., Zhou, C.-Y., Wang, L.-X., Zhou, Q.-L. JACS 129, 2248 (2007). 25 Duan, H.-F., Xie, J.-H., Qiao, X.-C., Wang, L.-X., Zhou, Q.-L. ACIE 47, 4351 (2008). 26 Zuend, S.J., Jacobsen, E.N. JACS 129, 15872 (2007). 27 Wang, W., Gou, S., Liu, X., Feng, X. SL 2875 (2007). 28 Chen, S.-K., Peng, D., Zhou, H., Wang, L.-W., Chen, F.-X., Feng, X.-M. EJOC 639 (2007). 29 Wang, S.-X., Wang, M.-X., Wang, D.-X., Zhu, J. ACIE 47, 388 (2008). 7

Aldol reaction has a new list of chiral catalysts, and they include 61,1 62,2 and 63.3 The presence of a hydrophobic silyl group to mask the hydroxyl residue of serine in 63 is important, L-serine itself being inactive is an indication. O

N N N H H H ·CF3COOH

H

O

NH2 Si

N H N H R ·HX

(61)

Ph

O

COOH

Ph

(62)

(63)

The dipeptide-derived 64 4 is a suitable aldol reaction catalyst for handling haloacetones and a-hydroxyacetone, and the the water-compatibility of the analogous 65 underscores its utility in the reaction involving a,a0 -dihydroxyacetone.5

O

NH2

Ar N H

(64)

O

O

Ar OH

NH2

Ph N H

(65)

Ph Ph

OH

118

Chiral auxiliaries and catalysts

The chiral aldol donor N-azidoacetyl-4-phenylthiazolidine-2-thione forms a stable titanium enolate on treatment with TiCl4 and i-Pr2NEt in NMP and CH2Cl2 at –788.6 syn-Selective aldol reaction of 1,1-dimethoxy-2-alkanones is accomplished in the presence of diamine 66A.7 Also reported for other aldol reactions is 66B.8 The amide derived from phenylalanine and bispidine (67) promotes aldol reaction of functionalized ketone receptors.9 O

NR2

HN

N NH2

NH2

Ph

(67)

(66A) R = n-C10H21 (66B) R = n-C3H7

Chiral 3-hydroxyoxindoles can be synthesized from isatin by an asymmetric aldol reaction. The prolinamide 68 possesses just the right attributes of a catalyst to meet the demand.10

Ph

Ph

O

O NH HN

H

NH

(68) b-Hydroxyalkanitriles containing a chiral quaternary a-carbon atom are available from condensation of N-silyl ketene imines with aldehydes. The process is mediated by SiCl4, and chiral information comes from 69.11

N

O P

N

CH2

N 2

(69) ArCHO R

SiCl4 (69)

C N-TBS R'

OH +

CN

Ar R

R'

Chiral auxiliaries and catalysts

119

Metal chelates that ﬁnd use as aldol reaction catalysts are further exempliﬁed by the Al complex of salen 60, which brings together a-isocyano amides and aldehyds to provide chiral 2-(a-hydroxyalkyl)-5-aminooxazoles.12

OH RCHO +

R (60)-AlCl

O

O

CN

N NR"2

NR"2 R'

R'

Copper(II) complexes of two imino nitrogen atoms belonging to chiral oxazoline and sulfoximine moieties (70) are able to elicit asymmetric consequences in the Mukaiyamaaldol reaction of enol silyl ethers and a-keto esters.13

N

S Ph O

O *

N *

Ph

(70) Reductive aldol reaction of 1-alken-3-ones and cinnamic esters depends on generating Rh enolates and the presence of chiral ligands turns such a process enantioselective. Effective ligands of very different structural types have been identiﬁed, and they include TADDOL phosphine 71 14 and BOX ligand 72.15

O O

O P O

(71)

N S

O

O N

N

(72)

Copper hydride species generated in situ from hydrophenylsilane and a CuF complex initiates reductive aldol reaction by forming copper enolates (rather than enol silyl ethers). For accomplising a chiral reaction the ferrocenyl ligand 73 is added.16

120

Chiral auxiliaries and catalysts

PCy2 NMe2 PCy2

O

MeOOC

+ Ph

Fe (Ph3P)3CuF · 2MeOH (73)

(73)

PhSiH3

OH MeOOC

Ph

98% (95% ee)

With a Ph-BOX ligand (e.g., ent-1B) to complex Cu(OTf)2 for decarboxylative aldol reaction of substituted malonic acid monothioesters, syn-selectivity is observed.17 This reaction operates on a different mechanism than enzyme-catalyzed decarboxylative Claisen condensation. Intramolecular aldol reaction forms 3-hydroxycycloalkanones. Catalysis by natural a-amino acids reveals some unusual results: there is enantio-reversal in closing a 7-membered ring as compared with closure leading to 3-hydroxycyclohexanones.18 Parenthetically, retroaldol cleavage of allyl bicyclo[3.2.0]heptan-2-on-5-yl carbonates gives 5-allyl-1,4-cycloheptanediones by asymmetric induction of 7.19 O

O (dba)3Pd2 (7)

O

O O

O

A ternary chelate of TiCl4, sparteine and the N-acetyl derivative of the tricyclic thiazolidinethione 74 acts as a chiral donor in aldol reaction with aldehydes.20 The tryptophanderived oxazaborolidinone 75 is serviceable in completing the vinylogous Mukaiyama aldol reaction to furnish chiral products.21

O H H N

S

O N B Ph Ts

H

S N H

H

(74)

(75)

Chiral auxiliaries and catalysts

121

The asymmetric Henry reaction22 is important because products are convertible to many other valuable bifunctional or polyfunctional compounds. Organocatalysts for the reaction containing a guanidine unit are represented by the C2-symmetric 76,23 which directs the addition of nitroalkanes to a-keto esters asymmetrically.

H N

F3C

N C8H37

H N O

N H Ph

N H Ph

H N

H N

CF3

S

CF3

CF3

(76) Tetraaminophosphonium salts such as 77 for catalyzing the Henry reaction have been developed.24 1,2-Diamines bearing chiral information to form metal complexes often can serve as catalyst for the reaction, and such is the case of N-(2-pyridylmethyl)isobornylamine (78) with Cu(OAc)2,25 and a Cu(II) complex of the salen 79.26 The bimetallic-salen complex 80A shows catalytic activity for bringing about anti-selective Henry reaction.27

H H Ar Ar

N

Ar N P

N

N Cl H

Ar H

(77) Ar = 4-FC6H4 Ph

N H

N

(78)

Ph

NH HN

N

OH HO

O O

(79)

N M O Ln OAr

O

(80A) M = Pd, Ln = La (80B) M = Cu, Ln = Sm

The C2-symmetric ligands bis-N-oxide 55 28 and cyclohexane spiroannulated to two oxazolidine units 81,29 in pairing with In(OTf)3, and Me2Zn, respectively, form active promoters for the addition of MeNO2 to carbonyl compounds.

122

Chiral auxiliaries and catalysts

H

H H N

O

NH O H H

(81) Acylsilanes are umpolung reagents that direct C-acylation of nitrones to give a-siloxyamino ketones. A TADDOL phosphite (82) engenders the reaction asymmetric.30 O Ph

Ph O O P O H

O O Ph

Ph

Ar

SiMe3

O

+ –

O

+

N

Ar"

Ar

(82)

OSiMe3 N Ar" Ar'

Ar'

(82) The carbonyl-ene reaction is a source of homoallylic alcohols, although the scope is somewhat limited. Synthesis of chiral tertiary a-hydroxycarboxylic esters from glyoxylic esters has been studied, and many metal catalysts of varying degree of effectiveness have been identiﬁed. The Ag-catalyzed reaction between enol silyl ethers and a glyoxylic ester is sterically controlled by the Pd-SEGPHOS complex.31 Other metal complexes reported for catalytic activities for the carbonyl-ene reaction are 83,32 84,33 and Cu(OTf)2-85.34

Ph

H

Ph

N

H N

N

i Bu

3Si

Br

O

O

H

H

Cl

H

O

N N O

H

(85)

SbF6 Si i Bu3

(83) 1

H

Cr

Co O

H O

(84)

Lacoste, E., Vaique, E., Berlande, M., Pianet, I., Vincent, J.-M., Landais, Y. EJOC 167 (2007). Kanger, T., Kriis, K., Laars, M., Kailas, T., Mu¨u¨risepp, A.-M., Pehk, T., Lopp, M. JOC 72, 5168 (2007). 3 Teo, Y.-C. TA 18, 1155 (2007). 4 Xu, X.-Y., Wang, Y.-Z., Gong, L.-Z. OL 9, 4247 (2007). 5 Ramasastry, S.S.V., Albertshofer, K., Utsumi, N., Babas III, C.F. OL 10, 1621 (2008). 2

Chiral auxiliaries and catalysts

123

6

Patel, J., Clave, G., Renard, P.-Y., Franck, X. ACIE 47, 4224 (2008). Luo, S., Xu, H., Chen, L., Cheng, J.-P. OL 10, 1775 (2008). 8 Luo, S., Xu, H., Li, J., Zhang, L., Cheng, J.-P. JACS 129, 3074 (2007). 9 Liu, J., Yang, Z., Wang, Z., Wang, F., Chen, X., Liu, X., Feng, X., Su, Z., Hu, C. JACS 130, 5654 (2008). 10 Chen, J.-R., Liu, X.-P., Zhu, X.-Y., Li, L., Qiao, Y.-F., Zhang, J.-M., Xiao, W.-J. T 63, 10437 (2007). 11 Denmark, S.E., Wilson, T.W., Burk, M.T., Heemstra Jr, J.R. JACS 129, 14864 (2007). 12 Wang, S.-X., Wang, M.-X., Wang, D.-X., Zhu, J. OL 9, 3615 (2007). 13 Sendelmeier, J., Hammerer, T., Bolm, C. OL 10, 917 (2008). 14 Bee, C., Han, S.B., Hassan, A., Krische, M.J. JACS 130, 2746 (2008). 15 Shiomi, T., Nishiyama, H. OL 9, 1651 (2007). 16 Deschamp, J., Chuzel, O., Hannedouche, J., Riant, O. ACIE 45, 1292 (2006). 17 Fortner, K.C., Shair, M.D. JACS 129, 1032 (2007). 18 Nagamine, T., Inomata, K., Endo, Y., Paquette, L.A. JOC 72, 123 (2007). 19 Schulz, S.R., Blechert, S. ACIE 46, 3966 (2007). 20 Osorio-Lozada, A., Olivo, H.F. OL 10, 617 (2008). 21 Simsek, S., Horzella, M., Kalesse, M. OL 9, 5637 (2007). 22 Palomo, C., Oiarbide, M., Laso, A. EJOC 2561 (2007). 23 Takada, K., Takemura, N., Cho, K., Sohtome, Y., Nagasawa, K. TL 49, 1623 (2008). 24 Uraguchi, D., Sasaki, S., Ooi, T. JACS 129, 12392 (2007). 25 Blay, G., Domingo, L.R., Hernandez-Olmos, V., Pedro, J.R. CEJ 14, 4725 (2008). 26 Xiong, Y., Wang, F., Huang, X., Wen, Y., Feng, X. CEJ 13, 829 (2007). 27 Handa, S., Nagawa, K., Sohtome, Y., Matsunaga, S., Shibasaki, M. ACIE 47, 3230 (2008). 28 Qin, B., Xiao, X., Liu, X., Huang, J., Wen, Y., Feng, X. JOC 72, 9323 (2007). 29 Liu, S., Wolf, C. OL 10, 1831 (2008). 30 Garrett, M.R., Tarr, J.C., Johnson, J.S. JACS 129, 12944 (2007). 31 Mikami, K., Kawakami, Y., Akiyama, K., Aikawa, K. JACS 129, 12950 (2007). 32 Hutson, G.E., Dave, A.H., Rawal, V.H. OL 9, 3869 (2007). 33 Grachan, M.L., Tudge, M.T., Jacobsen, E.N. ACIE 47, 1469 (2008). 34 Wakita, K., Bajracharya, G.B., Arai, M.A., Takizawa, S., Suzuki, T., Sasai, H. TA 18, 372 (2007). 7

Addition to CvN bond. Strecker-type synthesis, the addition of Me3SiCN to imines, on extending to N-phosphinoyl ketimines is enantioselective in the presence of 86, and the optimal conditions involve the addition of 10 mol% of MCPBA.1

O

NH

H

N

HN N

O H

(86) A titanium chelate of dihydroxylamine 87 helps organization of the addends so that a-amino nitriles of the (R)-conﬁguration are generated.2 Thiourea 88 with a proximal salen unit offers multiple hydrogen bonding sites for an analogous purpose of acetylcyanation of aldimines.3

124

Chiral auxiliaries and catalysts

S Me2N O

N H

N H

N

HO N H OH

Ph

O

OH

O

(88)

(87)

Organometallic reagents is subject to chiral modiﬁcation therefore their addition to imines is readily rendered enantioselective. In binding R2Zn during reaction N-(o-hydroxybenzyl)valylphenylalanine amides 89 are versatile modiﬁers, considering the possibility of tuning by variation of the aryl substituent. Forexample, a 3,5-di-t-butyl-2-hydroxybenzyl group is particularly suitable for the addition to the N-(o-methoxyphenyl)imines of triﬂuoroacetylarenes.4

R

H N

N H OH

O

O N H

Bu

Ph

(89) Diastereomeric benzylamines are obtained by cinnamylation of imines with alkenylsiladioxolane 90. The stereochemical switch requires only a change of the N-substituent.5 The cognate heterocycle 91 is useful catalyzing addition of ketene silyl ethers to hydrazones.6 HO

HO

HN

N Ph

Ph Ph

Ph

O Ph

Si N Cl Me

HO

(90)

HO N

Ph

HN Ph Ph

Ph

O

O

Si N Cl Me

(91)

Chiral auxiliaries and catalysts

125

There is no denying an important role is played by the phenolic OH of the N-aryl group to determine the favorable transition state, although the role is less apparent in the allylation of such imines by allylstannanes, in view of a rather complicated ligand (92) is being employed.7

O

O +

H

HN

NH – –

O

O N+

N

H

H

H

(92) Urea 93 is a bifunctional ligand possessing a Lewis basic sulﬁnamide group. Its use in guiding the addition of allylindium bromide to acylhydrazones has been explored.8 Allyl group transfer from B-allylpinacolatoboron to N0 -aroylhydrazonoacetic esters is catalyzed by a zinc salt bound to the diamine 94.9 (Results are less than satisfactory in view of products with ee ,90% being obtained.) CF3

Ph

Ph

O F3C

N H

N H

NH HN –

HN

+

S

O

OMe MeO

(94) (93) Chiral propargylic amines are formed by mixing aldehydes, o-anisidine, 1-alkynes with Me2Zn and amino alcohol 95.10 Alkynylation of pyridinium salts is guided by CuI which is complexed to the BOX ligand 96.11

Ph R HO

N

H OMe

R

O

O N

H

H

N H

OMe

(95)

(96A) R = H (96B) R + R = (CH2CH2)

126

Chiral auxiliaries and catalysts

The dihydroxybiaryl 97 can be used to exchange with alkenylboronate esters, bringing chirality in close proximity to the reaction site when the boronates participate in a Petasis reaction to build allylic amines.12 Ph Ph

OH OH

(97) Imines are generated in situ from N-Boc a-sulfonylamines, therefore the adducts are useful precursors for coupling with ArB(OH)2. Chiral benzhydrylamine derivatives are obtained when the Rh-catalyzed reaction is conducted in the presence of the pyrrolidinodiphosphine 98.13 Ph2P

PPh2 N Bn

(98) Synthesis of chiral allylic amines from alkynes and N-sulfonylaldimines involves reductive activation of the alkynes. The metal atom of iridacyclopropene intermediates also gathers the sulfonylimine as a bidentate ligand prior to bonding reorganization within the coordination sphere. The absolute stereochemical sense is governed by the chiral ligand employed (such as a member of the BIPHEP series).14 Articles summarizing current state of asymmetric addition to imines and highlighting Mannich reaction are available.15,16 Special attention has also been devoted the employment of organocatalysts for the Mannich reaction.17 O-Silylserine 63, the catalyst for aldol reaction, also actively promotes enantioselective Mannich reaction.18 Excellent asymmetric induction and anti-selectivity are found in the Mannich reaction using 3-pyrrolidinecarboxylic acids 99 19 and 3-triﬂylaminopyrrolidine 100.20 Since emphasis is placed on the importance of the carboxyl group of 99, the acidic TfNH group of 100 must be similarly implicated.

COOH R

N H

(99)

O HN S CF3 O N H

(100)

Chiral auxiliaries and catalysts

127

Considering the reactivity differences of ketones and esters as Mannich reaction donors the use of alkyl trichloromethyl ketones as surrogates of esters is a sound tactic. An asymmetric version is realized with a PYBOX ligated lanthanum aryloxide and LiOAr.21 Coordination of the widened BOX ligand 101 to Mg furnishes a catalyst capable of inducing asymmetric cycloaddition of 3-(isothiocyanatoacetyl)-2-oxazolidinone with N-tosylaldimines, furnishing precursors of chiral a,b-diamino acids.22

O

O N

O N Ph

Ph

(101) The higher reactivity of enol silyl ethers can be exploited in their reaction with imines. For addition to N-phosphonyl imines two types (SEGPHOS and DuPHOS) of ligands accommodate the variant substrates.23 The C2-symmetric cyclohexane 102 that carries two thiourea groups induces the asymmetric coupling of a triphenylphosphoranylacetic ester with aldimines to give stabilized Wittig reagents containing a chirality center.24

F3C

CF3

EtOOC

+

NBoc

PPh3 S

NH

R

(102)

NH

NHBoc EtOOC R

NH S

PPh3

NH HCHO

F3C

CF3

(102)

NHBoc EtOOC R

A urea (103) having the two nitrogen atoms as part of a b-amino alcohol and a sulﬁnamide, respectively, is endowed with interactive components to arrange the absolute conﬁguration whereby nitroalkanes and aldimines react.25 Thioureas 104 26 and 105B 27 are other such devices.

128

Chiral auxiliaries and catalysts

CF3 O S

S

O N H

N H

O

N H

N

OH

(104)

OAc H N

O OAc

CF3

Ph

(103)

AcO AcO

N H

NR2

H N S

(105A) R = H (105B) R = Me A successful screening of the multitasking dinuclear zinc alkoxide 106 for catalyzing the aza-Henry reaction is no surprise.28 On the other hand, identiﬁcation of the heterobimetallic chelate 80B is a new development.29 The syn : anti product ratio of .20: 1 and 83–98% ee in many cases vouchsafe for a general utility of the catalyst. Ph

Me

O

Ph

O

Zn Zn N O

N

Ph Ph

(106) A monotriﬂate of tetramine (107) is used to engender the asymmetric addition of a-nitroalkanoic esters to imines.30 The work seems to follow an evolving trend of partially perturbing highly efﬁcient C2-symmetric ligands in attempt to optimize their performance.

MeO NH HN N

+

N

H TfO

–

(107)

Chiral auxiliaries and catalysts

129

Camphor modiﬁed by replacing the 10-methyl group with a thiabicyclo[2.2.1]heptane nucleus (108) exerts chiral inﬂuences on the aza-Baylis–Hillman reaction.31

O

H S

(108) An a,b-unsaturated aldehyde adds to a nitrone to give g-hydroxylaminoalkanoic ester when the substrates are exposed to an azolecarbene, and the reaction mixture is quenched by an alcohol. Homoenolate ion generated from the aldehyde and the carbene is the nucleophile. The use of carbene 109 engenders chiral products.32 CHO

N

O N

Ph

N Ph

+

Ph BF4

(109)

O

N

Ph

(109) DBU; MeOH

MeOOC Ph

OH N Ph Ph

Ph

Closely related to imines are azodicarboxylic esters. Asymmetric amination is of course an important subject and a report on the utility of iridium complex 3 is on record.33 1

Huang, J., Liu, X., Wen, Y., Qin, B., Feng, X. JOC 72, 204 (2007). Banphavichit, V., Bhanthumravin, W., Vilaivan, T. T 63, 8727 (2007). 3 Pan, S.C., List, B. OL 9, 1149 (2007). 4 Fu, P., Snapper, M.L., Hoveyda, A.H. JACS 130, 5530 (2008). 5 Huber, J.D., Leighton, J.L. JACS 129, 14552 (2007). 6 Notte, G.T., Leighton, J.L. JACS 130, 6676 (2008). 7 Li, X., Liu, X., Fu, Y., Wang, L., Zhou, L., Feng, X. CEJ 14, 4796 (2008). 8 Tan, K.L., Jacobsen, E.N. ACIE 46, 1315 (2007). 9 Fujita, M., Nagano, T., Schneider, U., Hamada, T., Ogawa, C., Kobayashi, S. JACS 130, 2914 (2008). 10 Zani, L., Eichhorn, T., Bolm, C. CEJ 13, 2587 (2007). 11 Sun, Z., Yu, S., Ding, Z., Ma, D. JACS 129, 9300 (2007). 12 Lou, S., Schaus, S.E. JACS 130, 6922 (2008). 13 Nakagawa, H., Rech, J.C., Sindelar, R.W., Ellman, J.A. OL 9, 5155 (2007). 14 Ngai, M.-Y., Barchuk, A., Krische, M.J. JACS 129, 12644 (2007). 15 Ferraris, D. T 63, 9581 (2007). 16 Marques, M.M.B. ACIE 45, 348 (2006). 17 Ting, A., Schaus, S.E. EJOC 5797 (2007). 18 Teo, Y.-C., Lau, J.-J., Wu, M.-C. TA 19, 186 (2008). 19 Zhang, H., Mitsumori, S., Utsumi, N., Imai, M., Garcia-Delgado, N., Mifsud, M., Albertshofer, K., Cheong, P.H.-Y., Houk, K.N., Tanaka, F., Barbas III, C.F. JACS 130, 875 (2008). 2

130

Chiral auxiliaries and catalysts

20

Pouliquen, M., Blanchet, J., Lasne, M.-C., Rouden, J. OL 10, 1029 (2008). Marimoto, H., Lu, G., Aoyama, N., Matsunaga, S., Shibasaki, M. JACS 129, 9588 (2007). 22 Cutting, G.A., Stainforth, N.E., John, M.P., Kociok-Ko¨hn, G., Willis, M.C. JACS 129, 10632 (2007). 23 Suto, Y., Kanai, M., Shibasaki, M. JACS 129, 500 (2007). 24 Zhang, Y., Liu, Y.-K., Kang, T.-R., Hu, Z.-K., Chen, Y.-C. JACS 130, 2456 (2008). 25 Robak, M.T., Trincado, M., Ellman, J.A. JACS 129, 15110 (2007). 26 Chang, Y., Yang, J., Dang, J., Xue, Y. SL 2283 (2007). 27 Wang, C., Zhou, Z., Tang, C. OL 10, 1707 (2008). 28 Trost, B.M., Lupton, D.W. OL 9, 2023 (2007). 29 Handa, S., Gnanadesikan, V., Matsunaga, S., Shibasaki, M. JACS 129, 4900 (2007). 30 Singh, A., Johnston, J.N. JACS 130, 5866 (2008). 31 Myers, E.L., de Vries, J.G., Aggarwal, V.K. ACIE 46, 1893 (2007). 32 Phillips, E.M., Reynolds, T.E., Scheidt, K.A. JACS 130, 2416 (2008). 33 Hasegawa, Y., Watanabe, M., Gridnev, I.D., Ikariya, T. JACS 130, 2158 (2008). 21

Conjugate additions. Organocatalysis is enjoying great popularity, therefore a host of information has accumulated. Past years have witnessed publication of reviews on the usage of organocatalysts for conjugate additions.1,2 While many of these catalysts are derived from (S)-proline and cinchona alkaloids, the tryptophan derivative 20B has found an application in mediating transfer of alkenyl groups (from potassium alkenyltriﬂuoroborates) to 2-butenal.3 Asymmetric addition of split TBS-CN to enones is effectively performed by a gadolinium complex of 110.4 Traditional conjugate addition of organometallic reagents in the presence of a copper salt is subject to intervention by chiral ligands, and the discovery that simple monodentates such as 111 works well (addition of R2Zn and R3Al) is a revelation.5 The congeneric O,O0 -biaryl phosphoramidite 112 shows the same level of activity as expected.6 Ph O

Ph P

HO O

X

HO

Y

(110) X = Y = F X = CN, Y = H

P N

(111)

O P N O

(112)

Chiral auxiliaries and catalysts

131

A ﬂexible biphenyl residue contributes to the effectiveness of such ligands (113, 114) for the Rh-catalyzed delivery of aryl groups from ArB(OH)2 to enones.7 But for the conjugate addition of a bulky alkyne to enones the pairing of Rh(I) with SEGPHOS 16A is designed for exploiting steric advantages.8 Ph

Ph O P N O Ph

O P O O

(113)

(114)

Copper(II) triﬂate forms many complexes with BOX ligands including 1E, which negotiates the delivery of the allyl group from allyltrimethylsilane to a-methoxycarbonylated cycloalkenones while establishing a new stereocenter in the (R)-conﬁguration.9

O

O N

N

(1E) Calcium isopropoxide complexed to the simplest Ph-BOX ligand serves as a Bronsted base and chiral catalyst for rendering glycine t-butyl ester into a nucleophile toward acrylic esters.10 Aryl transfer from ArSi(OEt)3 to conjugated ketones, lactones and lactams is achieved with the aid of a palladium(II) salt supported by 116.11 It is a variation of the reaction involving ArB(OH)2 with a similar system. The P,P0 -dioxide of the same ligand complements CuOTf to serve as catalyst for the addition of R2Zn to nitroalkenes.12

P

P

(116)

132

Chiral auxiliaries and catalysts

The Cu(II) complex of 117 outperforms the congener possessing a BINOL moiety in conjugate addition of organometallics to nitroalkenes, the o,o0 -dioxydiphenylmethane unit is subject to conformational changes as determined by the bis-(a-phenethyl)amino chirality.13

O

Ph P N

O

Ph

(117) Ferrocenyldiphosphine 118A issues chiral information on complexation to CuBr to direct 1,6-addition of Grignard reagents to a,b; g,d-unsaturated carbonyl compounds.14

PR2 PR'2 Fe

(118A) (118B) (118C) (118D)

R = Ph, R' = Cy R = R' = Ph R = Cy, R' = Ph R = t-Bu, R' = Ph

A series of 1,2-diarylethane-1,2-diamines and/or their metal complexes are effective conjugate addition catalysts involving stabilized donors. In reaction of enamides with alkylidenemalonic esters15 a Cu(II) complex of 119 is employed, whereas the strontium complex of the bis(sulfonamide) 120 mediates the addition of malonic esters to enones.16 Ph

Ph

NH HN

(119)

Ph Ph O O O S NH HN S O

(120)

The differentially modiﬁed diamine 121, having an areneulfonyl substituent at one end and a thiocarbamoyl group attached to the other nitrogen atom, tests well for catalytic activity in the addition of b-diketones to nitroalkenes.17 Incorporation of the two amino groups into a

Chiral auxiliaries and catalysts

133

cyclic guanidine, resulting in 122, a new chiral catalyst for addition of t-butyl diphenylmethyleneiminoacetate to acrylic esters.18 Ph Ph

S

Ph

N H HN SO2

F3C

N H

OH

N NMe2

N

N

CF3

(121)

(122)

Thiourea 123 while bearing only one chiral carbon atom is an adequate catalyst.19 Although much less commonly employed in the present context for calcium salts, one such appears to be able to team up with ent-96A to direct asymmetric Michael reaction involving a glycine derivative.20

NMe2 NH S

CF3

HN CF3

(123) An aluminum complex of 56 is found useful to direct enantioselective addition to conjugated ketophosphonates.21 Unusually concentrated efforts have been spent to optimizing the conjugate addition to nitroalkenes. Useful organocatalysts for ketones donors are 124,22 125,23 and 105A.24 The unsymmetrical 3,30 -dimorpholine 62 (R 5 i-Pr) is targeted for use in the case of aldehydes.25

N H N

N H N NR2

(124)

S NMe

(125)

134

Chiral auxiliaries and catalysts

Owing to its Lewis acidity, zinc complex 106 lends itself to schemes for alkylation of electron-rich arenes and heteroarenes such as pyrroles by way of conjugate addition.26 An even more valuable method is the 3-component condensation that unites indole with a nitroalkene and an aldehyde. Three contiguous stereocenters are established in a controlled manner and in an absolute sense by conducting the reaction in the presence of CuOTf, 126, and hexaﬂuoroisopropanol.27

R Ph

Ph +

Ts N

N

N H

OH Br

N

NO2 R'CHO

CuOTf

(CF3)2CHOH

(126)

PhMe

Ph Br

HO R'

R

(126)

NO2 N H

A synthesis of chiral 5-substituted 3-pyrazolidinones involves addition of hydrazines to conjugated imides, catalysis by the Mg complex of 96B.28 Initiated by conjugate addition of iodide ion, which is under stereocontrol by the chiral auxiliary of an N-alkenyl-2-oxazolidinone, a tandem intramolecular alkylation is also enantioselective. Based on this reasoning it is possible to prepare cyclic compounds with new stereocenters of deﬁned absolute conﬁguration.29

O EtO

N

O

O

TiCl4 Bu4NI EtOAc-CH2Cl2

R

(4 : 1)

R = Ph, Bn

1

Almasi, D., Alonso, D.A., Najera, C. TA 18, 299 (2007). Tsogoeva, S.B. EJOC 1701 (2007). 3 Lee, S., MacMillan, D.W.C. JACS 129, 15438 (2007). 4 Tanaka, Y., Kanai, M., Shibasaki, M. JACS 130, 6072 (2008). 2

O H

O N

O N

H I R

O

Chiral auxiliaries and catalysts

135

5

Palais, L., Mikhel, I.S., Bournaud, C., Micouin, L., Falciola, C.A., Vuagnoux-d’Augustin, M., Rosset, S., Bernardinelli, G., Alexakis, A. ACIE 46, 7462 (2007). 6 Vagnoux-d’Augustin, M., Kehrli, S., Alexakis, A. SL 2057 (2007). 7 Monti, C., Gennari, C., Piarulli, U. CEJ 13, 1547 (2007). 8 Nishimura, T., Guo, X.-X., Uchiyama, N., Katoh, T., Hayashi, T. JACS 130, 1576 (2008). 9 Shizuka, M., Snapper, M.L. ACIE 47, 5049 (2008). 10 Saito, S., Tsubogo, T., Kobayashi, S. JACS 129, 5364 (2007). 11 Gini, F., Hessen, B., Feringa, B.L., Minnaard, A.J. CC 710 (2007). 12 Cote, A., Lindsay, V.N.G., Charette, A.B. OL 9, 85 (2007). 13 Wakabayashi, K., Aikawa, K., Kawauchi, S., Mikami, K. JACS 130, 5012 (2008). 14 den Hartog, T., Harutyunyan, S.R., Font, D., Minnaard, A.J., Feringa, B.L. ACIE 47, 398 (2008). 15 Berthiol, F., Matsubara, R., Kawai, N., Kobayashi, S. ACIE 46, 7803 (2007). 16 Agostinho, M., Kobayashi, S. JACS 130, 2430 (2008). 17 Wang, C.-J., Zhang, Z.-H., Dong, X.-Q., Wu, X.-J. CC 1431 (2008). 18 Ryoda, A., Yajima, N., Haga, T., Kumamoto, T., Nakanishi, W., Kawahata, M., Yamaguchi, K., Ishikawa, T. JOC 73, 133 (2008). 19 Andres, J.M., Manzano, R., Pedrosa, R. CEJ 14, 5116 (2008). 20 Kobayashi, S., Tsubogo, T., Saito, S., Yamashita, Y. OL 10, 807 (2008). 21 Takenaka, N., Abell, J.P., Yamamoto, H. JACS 129, 742 (2007). 22 Ishii, T., Fujioka, S., Sekiguchi, Y., Kotsuki, H. JACS 126, 9558 (2004). 23 Xu, D.-Q., Wang, L.-P., Luo, S.-P., Wang, Y.-F., Zhang, S., Xu, Z.-Y. EJOC 1049 (2008). 24 Liu, K., Cui, H.-F., Nie, J., Dong, K.-Y., Li, X.-J., Ma, J.-A. OL 9, 923 (2007). 25 Sulzer-Mosse, S., Laars, M., Kriis, K., Kanger, T., Alexakis, A. S 1729 (2007). 26 Trost, B.M., Mu¨ller, C. JACS 130, 2438 (2008). 27 Arai, T., Yokoyama, N. ACIE 47, 4989 (2008). 28 Sibi, M., Soeta, T. JACS 129, 4522 (2007). 29 Koseki, Y., Fujino, K., Takeshita, A., Sato, H., Nagasaka, T. TA 18, 1533 (2007).

Cycloadditions. Asymmetric Simmons –Smith reaction of allylic alcohols performed in the presence of an aluminum complex of the salen 127 has been reported.1

N

N

OH HO Ph Ph

(127) A Cu complex of the bispidine 128 catalyzes the decomposition of ethyl diazoacetate. Trapping of the carbenoid with alkenes (e.g., styrene) gives chiral cyclopropanecarboxylic esters. In the case of styrene, ethyl cis-2-phenylcyclopropanecarboxylate is obtained in 91% ee, although much lower value (79% ee) for the trans-isomer. Both products have an

136

Chiral auxiliaries and catalysts

(S)-conﬁguration at C-1.2 With a change to the Ir complex of salen 127 in which the metal is also s-bonded to an aromatic ring, t-butyl cis-2-arylcyclopropanecarboxylates are obtained almost exclusively and ee value reaches 97 –99%.3 O N MeN

(128) 3-Substituted (2R,3R)-ethyl aziridine-2-carboxylates are synthesized from imines and ethyl diazoacetate. The catalyst system is composed from (PhO)3B and (S)-VAPOL.4 Asymmetric cyclopropanation of electron-deﬁcient alkenes can be carried out with a Co(II) porphyrinate in which chiral substituents are set in two disjunct meso-positions.5 The presence of 129 6 or 130 7 renders the Corey–Chaykovsky method for cyclopropanation of conjugated aldehydes asymmetric. Thus it is easy to access (1S,2R)-2-formylcyclopropyl ketones from enals and acymethylsulfonium ylides.7

O N

N H

N HN N

N H

(129)

HN

S O O

(130)

Another modiﬁcation of the reaction entails the use of a La-Li3 complex of 131.8

OH

O O

OH

(131) Guanidinium ylide 132 generated in situ reacts with aldehydes to give aziridine-2carboxylic esters (cis/trans isomer mixtures).9 Chiral information located four bonds away is transmitted and it guides the alignment of the reactants.

Chiral auxiliaries and catalysts

Ph

137

O

N

MeN

O NMe

Ph

Ph

(132)

By forming adducts with azolecarbenes, cycloaddition of ketenes with imines to form b-lactams is facilitated. Azolecarbenes such as 133 10 and 134 11 induce chirality because in the enolates (initial adducts) the elements of asymmetry can dictate the approach of the reactants. Of particular interest is the reaction between enals and conjugated imines that leads to bicylic structures.11

N N

N Ph

H

Ph Ph

N

O N H

N

OTBS

(133) (134)

A powerful catalyst for [2þ2]cycloaddition is created from the bicyclic oxazaborolidine 135 and AlBr3. A hydrindanone frequently used in total synthesis of natural products is readily available from one such adduct in chiral form.12

H Ph N B

Ph

OTBS AlBr3

O

(135)

+

TBSO

O

CF3 O

COOCH2CF3

(135) Other notable catalysts are 136 13 and 137,14 the use of the latter is in conjunction with Cu(NTf2)2.

138

Chiral auxiliaries and catalysts

Ph H2N

N H

N H

N

O N

(136)

(137)

Molecules containing allene and alkene units that are separated by several bonds are subject to cycloisomerization. With a catalyst derived from AuCl and a SEGPHOS ligand 16, chiral products of formal [2þ2]cycloadditon are obtained.15 R R

R

C

H (16)

Z

CH2Cl2

Ar

R

Z H

Ar

Asymmetric 1,3-dipolar cycloaddition reactions have been reviewed,16 but ongoing research is still vigorous. The effectiveness of 138, a phosphine modiﬁed from serine, for synthesizing cyclopentenecarboxylic esters from 2,3-alkadienoic esters and electrondeﬁcient alkenes has been validated.17 Phosphine-thiourea 139 is useful for directing enantioselective combination of allenes and imines.18

Boc

H N

Ph2P

COOBn

COOBn COOMe

+ R"

C H

(138)

R" R

R R'

(138)

O

R'

O S Bn2N O

N H

N H

PPh2

(139) Besides organocatalysts, metal complexes show catalytic activities in various types of [3þ2]cycloaddition. Thus Ru complex 140 performs a role in the reaction of nitrile oxides with enals,19 and gold(I) benzoate complex of Cy-SEGPHOS is involved in the reaction of mu¨nchnones with alkenes.20

Chiral auxiliaries and catalysts

139

Ru O Ar2P O PAr2 O SbF6

Ph

Ph

(140) Ar = C6F5 Azomethine ylides are typical 1,3-dipoles, their participation in [3þ2]cycloaddition is greatly inﬂuenced by Cu catalysts. Asymmetric reactions are realized by the addition of chiral ferrocene ligands such as 141 (called Fesulphos)21 and 142.22

S Fe

PPh2

PPh2 Fe

(141)

N N N

PPh2 Ph

(142)

The ferrocenyl P,N-ligands 143A and 143B differ in ability to form hydrogen bonds in the transition state of 1,3-dipolar cyloaddition involving azomethine ylides and dimethyl maleate, and they give rise to adducts of opposite enantiomeric series.23

PAr2 Fe

NR2

(143A) R = H (143B) R = Me

An analogous ligand in which the amino group (of 143A/B) is replaced by a p-anisylthio residue has also been scrutinized.24 Decomposition of an aryl diazoacetate by CuOTf in the presence of a conjugated carbonyl compound leads to a 2,3-dihydrofuran-2-carboxylate, the result of a formal [4þ1]cycloaddition. To acquire a chiral product the presence of bipyridyl 144 is needed.25

140

Chiral auxiliaries and catalysts

COOAr Fe N

O +

N

COOAr

N2

CuOTf

O

(144)

Fe R

R'

R

R'

(144) The great importance of the Diels –Alder and hetero-Diels –Alder reactions in synthesis is a strong stimulus for ﬁnding new aspects about them, especially those methodologically related, and chiral catalysts rank high in such a context. Accordingly, 145,26 1D,27 and 146 28 are valuable additions to the list of the metal-free entities, even 1D is somewhat inferior due to relatively low asymmetric induction (up to 70% ee) it tenders during the reaction of anthrones and maleimides. Ph

S O

H

H NH NEt

Ph N

O

B Ph

(MeSO2)2CC6F5

O

(145)

(146)

The versatility of 135-AlBr3 complex for catalyzing enantioselective reactions is further demonstrated by its gainful use in the Diels –Alder reaction.29 Cu-BOX 147 is reusable and it is recovered from the reaction mixture by precipitation as a charge complex with a trinitroﬂuorenone.30 The nickel complex of 101 is effective in catalyzing the hetero-Diels –Alder reaction of N-sulfonyl-1-aza-1,3-dienes with enol ethers.31 O N

O

Cu O

N

OTf OTf

(147) Cu-BOX ligands show desirable afﬁnity for alkenyl 2-(N-oxidopyridyl) ketones, and they are useful asymmetric inducers in the Diels–Alder reaction.32 The corresponding pyridyl ketones form adducts with low ee, indicating the transition state for a large portion of the reaction does not involve such a metal complex, even if it is present.

Chiral auxiliaries and catalysts

141

Siloxymethyl alkenyl ketones 148, in which chirality is created by placing a methoxy substituent at an a-carbon of the silyl group, form complexes with Mg(OTf)2 to become chiral dienophiles.33 2-(1-Methylimidazolyl) alkenyl ketones undergo enantioselective Diels–Alder reaction in water, in the presence of a DNA-based catalyst.34 OMe Ph3C

Si

O O

R

(148) It is found that chiral dienes form better performing cationic Rh complexes than diphosphines, for use in catalyzing intramolecular Diels–Alder reaction of conjugate diene and alkyne units.35 A cationic Ru(I) catalyst 140 operates on the basis of one-point association of the dienophile prior to establishment of the transition state for the Diels –Alder reaction. The most effective case demonstrated thus far is an intramolecular process.36

(140)

O H

O

By ensconcing an In(III) ion in the N-oxide 55B originated from two homochiral pipecolinic amides a catalyst for hetero-Diels –Alder reaction involving the Danishefsky diene and aldehydes is obtained.37 Cr(salen) 149 appears to have similar capability.38

MeO H

N

O

R

O Cr

O

+

Cl

OSiMe3

H

(149)

(149)

MeO

HF-Py, MeOH

O

R

O

A representative of the hetero-Diels –Alder reaction of inverse electron demand is the cycloaddition of N-sulfonyl-1-azadienes with vinyl ethers. It is amenable to asymmetric catalysis, for example, by a nickel(II) complex of 101.39

142

Chiral auxiliaries and catalysts

When a conjugated ketene generated in situ adds to the Er(III) complex of amino alcohol 150, its conformation is ﬁxed. The metal center also attracts an aldehyde to proceed with the hetero-Diels –Alder reaction.40 Ph

OH N

(150) Adducts of diorganozinc reagents with ethyl 2,3-butadienoate also show diene character toward the carbonyl group. The hetero-Diels –Alder reaction is asymmetrized in the presence of Cu(OAc)2 and DIFLUORPHOS.41 Synthesis of tropanes by a [4þ3]cycloaddition becomes asymmetric when it is directed by the Rh carboxylate 151.42

O

N H

O O

Rh

O 4

Rh

(151) The Pauson–Khand reaction belongs to the [2þ2þ1]cycloaddition category. The Rh-catalyzed version is made asymmetric by ligating the metal center to 152.43 Substratecontrol via 1,3-asymmetric induction for the establishment of a new stereocenter at C-4 of the emerging cyclopentenone system is the key to an approach to the hemigerans.44 OMe N

MeO N

OMe

MeO PPh2

Ph2P

(152) OH OH

Co2(CO)8

O

Si

O

PhMe

O

Si

O

70%

O

Chiral auxiliaries and catalysts

143

Bicyclic enones originated from 1,6-enynes are also prepared using the (cod)IrPF6 complex of 7.45 In the elaboration of cyclopentenones the Nazarov cyclization (not a cycloaddition reaction) also offers some advantages. Metal complexes including a V(IV) chelate of salen 60 46 and the Cu complex of ent-96B 47 have been employed as catalysts. By structural demand of the substrate to induce rearrangement following the cyclization a synthesis of spirocycles is realized.

O

O COOMe ent-(96B)

COOMe

ClCH2CH2Cl

R

100°

R R = Pr 84%

Cross-conjugated dienones carrying a chiral auxiliary, suitable for Nazarov cyclization to provide chiral cyclopentenones, have been prepared from reaction of lithiated ethers 153/154 48 and 155 49 with N-alkenoylmorpholines.

TBSO TBSO

OTBS O

Ph O

1

O

Li C

(153)

O O

OTBS

O

Li

O Li

C TIPS

(154)

(155)

Shitama, H., Katsuki, T. ACIE 47, 2450 (2008). Lesme, G., Cattenati, C., Pilati, T., Sacchetti, A., Silvani, A. TA 18, 659 (2007). 3 Kanchiku, S., Suematsu, H., Matsumoto, K., Uchida, T., Katsuki, T. ACIE 46, 3889 (2007). 4 Lu, Z., Zhang, Y., Wulff, W.D. JACS 129, 7185 (2007). 5 Chen, Y., Ruppel, J.V., Zhang, X.P. JACS 129, 12074 (2007). 6 Hartikka, A., Arvidsson, P.I. JOC 72, 5874 (2007). 7 Hartikka, A., Slosarczyk, A.T., Arvidsson, P.I. TA 18, 1403 (2007). 8 Kakei, H., Sone, T., Sohtome, Y., Matsunaga, S., Shibasaki, M. JACS 129, 13410 (2007). 9 Disadee, W., Ishikawa, T. JOC 70, 9399 (2005). 10 Zhang, Y.-R., He, L., Wu, X., Shao, P.-L., Ye, S. OL 10, 277 (2008). 11 He, M., Bode, J.W. JACS 130, 418 (2008). 12 Canales, E., Corey, E.J. JACS 129, 12686 (2007). 13 Ishihara, K., Nakano, K. JACS 129, 8930 (2007). 14 Ishihara, K., Fushimi, M. JACS 130, 7532 (2008). 15 Luzung, M.R., Mauleon, P., Toste, F.D. JACS 129, 12402 (2007). 16 Pelliser, H. T 63, 3235 (2007). 17 Cowen, B.J., Miller, S.J. JACS 129, 10988 (2007). 2

144

Chiral auxiliaries and catalysts

18

Fang, Y.-Q., Jacobsen, E.N. JACS 130, 5660 (2008). Brinkman, Y., Madhushaw, R.J., Jazzar, R., Bernardinelli, G., Ku¨ndig, E.P. T 63, 8413 (2007). 20 Melhado, A.D., Luparia, M., Toste, F.D. JACS 129, 12638 (2007). 21 Cabrera, S., Arraya´s, R.G., Martı´n-Matute, B., Cossı´o, F.P., Carretero, J.C. T 63, 6587 (2007). 22 Fukuzawa, S., Oki, H. OL 10, 1747 (2008). 23 Zeng, W., Chen, G.-Y., Zhou, Y.-G., Li, Y.-X. JACS 129, 750 (2007). 24 Zeng, W., Zhou, Y.-G. TL 48, 4619 (2007). 25 Son, S., Fu, G.C. JACS 129, 1046 (2007). 26 He, H., Pei, B.-J., Chou, H.-H., Tian, T., Chan, W.-H., Lee, A.W.M. OL 10, 2421 (2008). 27 Akalay, D., Du¨rner, G., Go¨bel, M.W. EJOC 2365 (2008). 28 Payette, J.N., Yamamoto, H. JACS 129, 9536 (2007). 29 Liu, D., Canales, E., Corey, E.J. JACS 129, 1498 (2007). 30 Chollet, G., Guillerez, M.-G., Schulz, E. CEJ 13, 992 (2007). 31 Esquivias, J., Arraya´s, R.G., Carretero, J.C. JACS 129, 1480 (2007). 32 Barroso, S., Blay, G., Pedro, J.R. OL 9, 1983 (2007). 33 Campagna, M., Trzoss, M., Bienz, S. OL 9, 3793 (2007). 34 Boersma, A.J., Feringa, B.L., Roelfes, G. OL 9, 3647 (2007). 35 Shintani, R., Sannohe, Y., Tsuji, T., Hayashi, T. ACIE 46, 7277 (2007). 36 Rickerby, J., Vallet, M., Bernardinelli, G., Viton, F., Ku¨ndig, E.P. CEJ 13, 3354 (2007). 37 Yu, Z., Liu, X., Dong, Z., Xie, M., Feng, X. ACIE 47, 1308 (2008). 38 Dilger, A.K., Gopalsamuthiram, V., Burke, S.D. JACS 129, 16273 (2007). 39 Esquivias, J., Arraya´s, R.G., Carretero, J.C. JACS 129, 1480 (2007). 40 Tiseni, P.S., Peters, R. OL 10, 2019 (2008). 41 Oisaki, K., Zhao, D., Kanai, M., Shibasaki, M. JACS 129, 7439 (2007). 42 Reddy, R.P., Davies, H.M. JACS 129, 10312 (2007). 43 Lee, H.W., Kwong, F.Y., Chan, A.S.C. SL 1553 (2008). 44 Madu, C.E., Lovely, C.J. OL 9, 4697 (2007). 45 Lu, Z.-L., Neumann, E., Pfaltz, A. EJOC 4189 (2007). 46 Walz, I., Bertogg, A., Togni, A. EJOC 2650 (2007). 47 Huang, J., Frontier, A.J. JACS 129, 8060 (2007). 48 Banaag, A.R., Tius, M.A. JACS 129, 5328 (2007). 49 Dhoro, F., Kristensen, T.E., Stockman, V., Tius, M.A. JACS 129, 7256 (2007). 19

Epoxidation and other oxidation reactions. Regenerative pre-oxidants of the type 156A are derived from a pyranose. They are employed in conjunction with a expendable agent, such as oxone for epoxidation of conjugated cis-enynes,1 and H2O2 to epoxidize alkenes.2 O O

O

X O

O O

(156A) X = NAr (156B) X = O

Chiral auxiliaries and catalysts

145

Among new oxidation systems based on H2O2 for asymmetric epoxidation of styrenes the catalytic component comprises either the Ti(IV) complex of SALAN 157,3 or a mixture of FeCl3, 2,6-pyridinedicarboxylic acid, and 158.4

O O S NH Ph

NH HN OH HO MeO OMe

Ph

NH Bn

(158)

(157)

For enantioselective epoxidation of allylic alcohols with a hydroperoxide, a catalyst derived from vanadyl isopropoxide and a C2-symmetric (R,R)-bis[N-hydroxy-N-(3,3,3triarylpropanoyl)]-1,2-cyclohexanediamine has been developed5 Two chiral epoxidizing agents for enones are brucine N-oxide6 and cyclo(L-Pro-L-Pro) hydroperoxide,7 but the latter reagent produces epoxides of low ee. cis-Dimethoxylation of o-hydroxystyrenes with a bimetallic Pd-Cu catalyst system under O2 is enantioselective by the introduction of a chiral 2-(2-quinolyl)-4-isopropyloxazoline.8 L-Menthyl syn-3-amino-2-hydroxyalkanoates are acquired from menthyl acetate via enolization, Mannich reaction, and oxidation with an oxabornanesultam.9

O

2LDA/THF;

PMP NLi OLi

N-PMP

O

Ar

R*

O

Ar

O N O S O

DABCO

PMP NH

O

Ar

O

R*

OH

Optimization of asymmetric oxidation of sulﬁdes catalyzed by a Fe(salan) complex has been carried out.10 Using alkyl hydroperoxide as oxidant for sulﬁdes, a Ti(IV) chelate of

146

Chiral auxiliaries and catalysts

mixed tartaric esters in which one of the alkoxy residue is a v-methylated polyethylene glycol chain provides chiral instructions.11 Enantioselective oxidation of hindered disulﬁdes to monosulfoxides is accomplished in the presence of 156B.12 1

Burke, C.P., Shi, Y. JOC 72, 4093 (2007). Burke, C.P., Shu, L., Shi, Y. JOC 72, 6320 (2007). 3 Shimada, Y., Kondo, S., Ohara, Y., Matsumoto, K., Katsuki, T. SL 2445 (2007). 4 Gelalcha, F.G., Bitterlich, B., Anilkumar, G., Tse, M.K., Beller, M. ACIE 46, 7293 (2007). 5 Zhang, W., Yamamoto, H. JACS 129, 286 (2007). 6 Oh, K., Ryu, J. TL 49, 1935 (2008). 7 Kienle, M., Argyrakis, W., Baro, A., Laschat, S. TL 49, 1971 (2008). 8 Zhang, Y., Sigman, M.S. JACS 129, 3076 (2007). 9 Hata, S., Tomioka, K. T 63, 8514 (2007). 10 Egami, H., Katsuki, T. SL 1543 (2008). 11 Gao, J., Guo, H., Liu, S., Wang, M. TL 48, 8453 (2007). 12 Khiar, N., Mallouk, S., Valdivia, V., Bougrin, K., Souﬁaoui, M., Fernandez, I. OL 9, 1255 (2007). 2

Hydrogenation and reduction of CvC bonds. For asymmetric hydrogenation of styrenes several iridium complexes are serviceable. These metal complexes (e.g., 159,1 160,2 and 161 3) are prepared from [(cod)IrCl]2 via ligand exchange. In using complex 143 the best solvent seems to be propylene carbonate; high ee of 1-methyltetralin is obtainable from hydrogenation of 1-methylenetetralin, and lesser amount of substrate is isomerized to 1-methyl-3,4-dihydronaphthalene which undergoes hydrogenation to give the methyltetralin product in the enantiomeric series. A QUINAP complex of iridium is valued for asymmetric hydrogenation of styrenes.4 O

R

Ph

N

Me3Si

PPh2

O P O

M

Ir Ph

O N

O

Ph SiMe3

(159A) M = Fe, R = Me (159B) M = Ru, R = t-Bu

Ph

O O O

(160)

Ph P

Bn Bn

N O

(161) The complex 162 is an outstanding catalyst because it can be used in hydrogenation of unactivated tetrasubstituted alkenes.5 With 163 diastereoselective hydrogenation of farnesol

Chiral auxiliaries and catalysts

147

isomers is achieved: (E, E ) ! (R, R), (Z, E) ! (S, R), (E, Z) ! (R, S ), (Z, Z) ! (S, S), all with ee .99%.6 o-Tol Ir

o-Tol P

o-Tol

o-Tol BARF

N

P

O

Ir

O

BARF

N

(162)

(163)

Little or no C-F bond hydrogenolysis occurs during hydrogenation of ﬂuoroalkenes in the presence of catalyst 164 therefore its use on such occasions is recommended.7 Ph Ph

P

N

BARF

Ir N Ph

S

(164) Rh(I) supported by ferrocenylphosphines 165 shows comparable activity to that of the catalyst containing 107B (Josiphos) in hydrogenation of dimethyl itaconate,8 therefore no advantage is gained in its use. PPh2 P Fe PPh2

(165) A more complicated ferrocenylphosphine ligand is 166 and its complex with Rh(I) catalyzes asymmetric hydrogenation of b-phthalimidomethylcinnamic esters.9 CF3 F3 C P N

-Np Fe

P Ph

(166)

148

Chiral auxiliaries and catalysts

More Rh catalysts have been tested for the hydrogenation of dehydroamino ester derivatives. Two of them incorporate ligands 167 10 and 168.11 The latter seems to have a broader substrate scope, for example in reduction of acrylic esters. Also useful for the same purpose is an iridium(I) complex of 38B.12 Furthermore, 169 13 is active for hydrogenation of enol phosphinates.

O

Ph N H H N

(CH2)n

PPH2 N N

PPH2

O

P Ph Ph P

Ph

(167)

(168) o-Tol

o-Tol

P

Ir

N

N

H O BARF

(169) Rh complex 170 14 and the one derived from [(cod)2Rh]BF4 and diphosphine 171 15 are active in promoting reduction of a-ureido-a,b-unsaturated esters and enamides, respectively.

O

Cy

N Cy2P

Ph

N Rh

Ph

PPh2 Re PPh2 OC CO OC

(171) (170) N-Boc pyrroles are subject to partial or complete reduction. With a Ru complex and 2,20 -bis(1-diphenylphosphinoethyl)-1,10 -biferrocenyl ligand to effect hydrogenation chiral pyrrolidines are synthesized.16

Chiral auxiliaries and catalysts

149

Reductive amination of a-chloroacetophenones by trichlorosilane leads to benzylic amines which are useful precursors of 2-arylaziridines. Optically active amines are obtained when the reduction is conducted in the presence of a N-formyl-N-methylvalinamide.17 The conjugated double bond of a b-methylcinnamonitrile is reduced by PMHS, and since the reaction involves a copper hydride, the metal coordinated with a ligand such as 118C 18 forms a chiral catalyst. Similarly, reduction of conjugated esters is accomplished by PMHS with CuOAc and 118D present.19 Reduction of alkenyl sulfones is similarly manipulatable, and the P,P0 -dioxide of 116 is an alternative ligand for the copper center.20 Pinacolatoborylalkenes are subject to asymmetric hydrogenation using (nbd)2RhBF4 and 173 (Walphos 1).21 Secondary boronates thus acquired are sources of many chiral functional molecules.

F3C

CF3

Ph2P

N

CF3

Fe CF3

(173) 1

Li, X., Li, Q., Wu, X., Gao, Y., Xu, D., Kong, L. TA 18, 629 (2007). Dieguez, M., Mazuela, J., Pamies, O., Verendel, J.J., Andersson, P.G. JACS 130, 7208 (2008). 3 Bayardon, J., Holz, J., Scha¨ffner, B., Andrushko, V., Verevkin, S., Preetz, A., Bo¨rner, A. ACIE 46, 5971 (2007). 4 Li, X., Kong, L., Gao, Y., Wang, X. TL 48, 3915 (2007). 5 Schrems, M.G., Neumaun, E., Pfaltz, A. ACIE 46, 8274 (2007). 6 Wang, A., Wu´´stenberg, B., Pfaltz, A. ACIE 47, 2298 (2008). 7 Engman, M., Diesen, J.S., Paptchikhine, A., Andersson, P.G. JACS 129, 4536 (2007). 8 Almassy, A., Barta, K., Francio, G., Sebesta, R., Leitner, W., Toma, S. TA 18, 1893 (2007). 9 Deng, J., Duan, Z.-C., Huang, J.-D., Hu, X.-P., Wang, D.-Y., Yu, S.-B., Xu, X.-F., Zheng, Z. OL 9, 4825 (2007). 10 Wei, H., Zhang, Y.J., Dai, Y., Zhang, J., Zhang, W. TL 49, 4106 (2008). 11 Fox, M.E., Jackson, M., Lennon, I.C., Klosin, J., Abboud, K.A. JOC 73, 775 (2008). 12 Giacomina, F., Meetsma, A., Panella, L., Lefort, L., de Vries, A.H.M., de Vries, J.G. ACIE 46, 1497 (2007). 13 Cheruku, P., Gohil, S., Andersson, P.G. OL 9, 1659 (2007). 14 Busacca, C.A., Lorenz, J.C., Grinberg, N., Haddad, N., Lee, H., Li, Z., Liang, M., Reeves, D., Sahe, A., Varsolona, R., Senanayake, C.H. OL 10, 341 (2008). 15 Stemmler, R.T., Bolm, C. TL 48, 6189 (2007). 16 Kuwano, R., Kashiwabara, M., Ohsumi, M., Kusano, H. JACS 130, 808 (2008). 17 Malkov, A.V., Stoncius, S., Kocovsky, P. ACIE 46, 3722 (2007). 18 Lee, D., Yang, Y., Yun, J. S 2233 (2007). 19 Lipshutz, B.H., Lee, C.-T., Servesko, J.M. OL 9, 4713 (2007). 20 Desrosiers, J.-N., Charette, A.B. ACIE 46, 5955 (2007). 21 Moran, W.J., Morken, J.P. OL 8, 2413 (2006). 2

150

Chiral auxiliaries and catalysts

Hydrogenation and reduction of CvO bond. Three metals make up the major classes of homogeneous hydrogenation catalysts for the reduction of the carbonyl group. A Cp Ir complex 3 with a bidentate ligand of monosulfonylated diphenylethanediamine is able to promote reduction of a-hydroxy ketones1 and with the same catalyst (or enantiomer) to rapidly transfer hydrogenate aryl ketones even in the air.2 For the latter purpose two other useful Ir complexes are that which contain the ligands 174 3 and 175.4

N

N

N

N

NH HN S

(174)

S

(175)

Transfer hydrogenation of aryl ketones from i-PrOH under basic conditions is also catalyzed by Rh(II) complexes. A series of 1,2-cyclohexanediamine arenesulfonamides 176 5 as well as the hydroxamic acid 177 6 derived from valine prove effective as chiral modiﬁers. Complexation of a chiral bis(o-[diphenylphosphino]ferrocenyl)-methanol [178 is the (R,R)-isomer] to a Rh(I) salt provides a hydrogenation catalyst for benzenesulfonylmethyl aryl ketones.7

OH

O O O S NH Ar

(176)

NH2

N H HN Boc

(177)

Ph2P OH Fe

Ph2P

Fe

(178)

Complexation of Rh or Ru center to N-a-phenethyl amides of N-Boc-a-thioamino acids (but not the amino acid derivatives) forms highly effective catalysts for asymmetric hydrogenation of aryl ketones.8 Following the long tradition of ruthenium-based complexes related to homogeneous hydrogenation of ketones, further studies have shown that biaryldiphosphines 179 9 and 16B 10 are valuable contributors of chiral instruction in forming catalysts for hydrogenating a-keto esters. In the employment of Ru(II)-16B the reduction of ethyl mesitoylformate is dramatically improved by CeCl3 . 7H2O, without which the conversion falls below 5%.

Chiral auxiliaries and catalysts

O

151

PAr2 PAr2

O

(179) Transfer hydrogenation of aryl ketones in the presence of 159B has been reported.11 Catalysts catering to reduction of chloromethyl aryl ketones and a-amino ketones are 180 12 and 181,13 respectively, besides their other uses. An analogue of 180 assists reduction of cyclic b-keto esters to cis-b-hydroxy esters by HCOOH –Et3N via dynamic kinetic resolution.14

Ph Ph

Cl H2 N Ru P N Cl H2 P

Ru NTs TfO Ph

H2N

Ph Ph

Ph Ph

Ph

(180)

(181)

a-Keto esters undergo transfer hydrogenation from Hantzsch esters and the process is rendered asymmetric by a BOX-Cu(OTf)2 complex.15 Diphosphine 37 forms a Pd complex to catalyze allylic substitution, and it also derives a Ru catalyst for asymmetric hydrogenation of b-keto esters.16 Hydrosilylation of aryl ketones is subject to sterocontrol by binding the metal catalyst with a chiral ligand. The reaction based on Fe(OAc)2 – PMHS is modiﬁed by 116,17 whereas the one catalyzed by AgBF4 and [(cod)MCl]2 is dominated by 182.18 Interestingly, a change of the central metal in the complex from Rh to Ir reverses the enantioselectivity.

O H

N

PPh2

OH Ph

(182)

152

Chiral auxiliaries and catalysts

When o-substituted aryl ketones are reduced using a copper catalyst, the steric course is inﬂuenced by (2S,4S)-bis(diphenylphosphino)pentane.19 The possibility of chiral modiﬁcation of NaBH4 for reduction of ketones has been scrutinized. Some success is reported by adding the inexpensive cyclic borinate 183 derived from tartaric acid and PhB(OH)2 to the reaction medium.20 Atropo-enantioselective reduction of biaryl lactones occurs on exposure to NaBH4 in the presence of the cobalt chelate 184.21 Ar O

Ar

COOH N

Ph B O

N Co

COOH

O

(183)

O

O

O

(184)

The (S )-diphenylprolinol-derived oxazaborolidine with an ethanediolated boron atom is a new catalyst for the asymmetric reduction of ketones with BH3 . SMe2.22 1,3-Cycloalkanediones undergo CBS-reduction to provide (3R)-hydroxycycloalkanones. Based on this method a very short synthesis of chiral estrone methyl ether is completed.23

O H

OH

Ph Ph

O NB

O MeO

Bu

O catecholborane

MeO 92% ee

estrone

1

Ohkuma, T., Utsumi, N., Watanabe, M., Tsutsumi, K., Arai, N., Murata, K. OL 9, 2565 (2007). Wu, X., Li, X., Zanotti-Gerosa, A., Pettman, A., Liu, J., Mills, A.J., Xiao, J. CEJ 14, 2209 (2008). 3 Shen, W.-Y., Zhang, H., Zhang, H.-L., Gao, J.-X. TA 18, 729 (2007). 4 Zhang, X.-Q., Li, Y.-Y., Zhang, H., Gao, J.-X. TA 18, 2049 (2007). 5 Cortez, N.A., Aguirre, G., Parra-Hake, M., Somanathan, R. TA 19, 1304 (2008). 6 Ahlford, K., Zaitsev, A.B., Ekstro¨m, J., Adolfsson, H. SL 2541 (2007). 7 Zhang, H.-L., Hou, X.-L., Dai, L.-X., Luo, Z.-B. TA 18, 224 (2007). 8 Zaitsev, A., Adolfsson, H. OL 8, 5129 (2006). 9 Sun, X., Zhou, L., Li, W., Zhang, X. JOC 73, 1143 (2008). 10 Meng, Q., Sun, Y., Ratovelomanana-Vidal, V., Genet, J.-P., Zhang, Z. JOC 73, 3842 (2008). 11 Liu, D., Xie, F., Zhao, X., Zhang, W. T 64, 3561 (2008). 12 Ohkuma, T., Tsutsumi, K., Utsumi, N., Arai, N., Noyori, R., Murata, K. OL 9, 255 (2007). 13 Liu, S., Xie, J.-H., Wang, L.-X., Zhou, Q.-L. ACIE 46, 7506 (2007). 2

Chiral auxiliaries and catalysts

153

14

Ros, A., Magriz, A., Dietrich, H., Lassaletta, J.M., Ferna´ndez, R. T 63, 7532 (2007). Yang, J.W., List, B. OL 8, 5653 (2006). 16 Imamoto, T., Nishimura, M., Koide, A., Yoshida, K. JOC 72, 7413 (2007). 17 Shaikh, N.S., Enthaler, S., Junge, K., Beller, M. ACIE 47, 2497 (2008). 18 Fro¨lander, A., Moberg, C. OL 9, 1371 (2007). 19 Shimizu, H., Igarashi, D., Kuriyama, W., Yusa, Y., Sayo, N., Saito, T. OL 9, 1655 (2007). 20 Eagon, S., Kim, J., Yan, K., Haddenham, D., Singaram, B. TL 48, 9025 (2007). 21 Ashizawa, T., Tanaka, S., Yamada, T. OL 10, 2521 (2008). 22 Stepanenko, V., De Jesus, M., Correa, W., Guzman, I., Vazquez, C., de la Cruz, W., Ortiz-Marciales, M., Barnes, C.L. TL 48, 5799 (2007). 23 Yeung, Y.-Y., Chein, R.-J., Corey, E.J. JACS 129, 10346 (2007). 15

Hydrogenation and reduction of CvN bond. Chiral Bronsted acids possessing a bulky backbone such as VAPOL derivative 9 attract and hold imine molecules in the concave space, and this reasoning has led to successful development of a protocol for the synthesis of a-amino acid derivatives from imino precursors by transfer hydrogenation (from Hantzsch ester).1 The iridium(I) salt containing 185 has also been employed as catalyst in hydrogenation of imines.2 In the hydrogenation of 2-substituted quinolines to provide chiral tetrahydro derivatives iridium complexes of SYNPHOS and DIFLUORPHOS prove to be effective catalysts.3,4 Oximes undergo enantioselective reduction (and NZO bond cleavage) on treatment with borane and spirocyclic boronate 186.5

Ph

Ph2P

N

Ph H2N

Fe

OMe

(185)

B

O

O O

(186)

Reduction via hydrosilylation with trichlorosilane does not requires a metal. Asymmetric reduction is achieved in the presence of the picolinic amide of (1R,2S)-ephedrine,6 or an S-chiral sulﬁnamide.7 1

Li, G., Liang, Y., Antilla, J.C. JACS 129, 5830 (2007). Cheemala, M.N., Knochel, P. OL 9, 3089 (2007). 3 Chan, S.H., Lam, K.H., Li, Y.-M., Xu, L., Tang, W., Lam, F.L., Lo, W.H., Yu, W.Y., Fan, Q., Chan, A.S.C. TA 18, 2625 (2007). 4 Deport, C., Buchotte, M., Abecassis, K., Tadaoka, H., Ayad, T., Ohshima, T., Genet, J.-P., Mashima, K., Ratovelomanana-Vidal, V. SL 2743 (2007). 5 Huang, K., Merced, F.G., Ortiz-Marciales, M., Melender, H.J., Correa, W., De Jesus, M. JOC 73, 4017 (2008). 6 Zheng, H., Deng, J., Lin, W., Zhang, X. TL 48, 7934 (2007). 7 Pei, D., Wang, Z., Wei, S., Zhang, Y., Sun, J. OL 8, 5913 (2006). 2

154

Chiral auxiliaries and catalysts

Isomerization and rearrangements. The 1,3-hydrogen shift of an enal to form ketene, when mediated by azolecarbene 109, generates a chiral intermediate which would add onto a proximal CvO group stereoselectively. Desymmetrization thus leads to a chiral cycloalkene on decarboxylation of the cycloadduct.1

O Ph

O Ph

Ph

O

Ph

O

O

O

(109)

Ph

Ph

H

CHO 93% ee

[2,3]Wittig rearrangement is rendered asymmetric by the presence of a BOX ligand (1E). The access to chiral aryl homoallyl carbinols in this manner is well adaptable to a synthetic route to lignans.2

TIPSO

TIPSO

t -BuLi (1E)

Ar

O

HO

Ar

The Overman rearrangement has been extended to the synthesis of secondary allyl aryl ethers3 and allylic thiol carbamates, using a palladized oxazolinylcobaltocene-type complex (187).4 The former reaction could very well be considered as an SN20 process.

Cl

2

Pd Ph Co Ph Ph

N O

Ph

(187) Ferrocenyl analogues 188,5 and a precatalyst version6 combined with a silver salt, have been tapped for enantioselective aza-Claisen rearrangement. Excellent asymmetric induction ensues.

Chiral auxiliaries and catalysts

Ph N

Ph

Cl Pd

155

2

N Ts

Ph Fe Ph Ph

Ph Ph

(188) Diastereoselective control during enolization of allyl esters for Claisen rearrangement leads to predeﬁned stereomers, and amide bases such as enantiomeric 189 are capable of generating chiral products.7

F3C

Li N

N

Ph

(189) 1

Wadamoto, M., Phillips, E.M., Reynolds, T.E., Scheidt, K.A. JACS 129, 10098 (2007). Hirokawa, Y., Kitamura, M., Maezaki, N. TA 19, 1167 (2008). 3 Kirsch, S.F., Overman, L.E., White, N.S. OL 9, 911 (2007). 4 Overman, L.E., Roberts, S.W., Sneddon, H.F. OL 10, 1485 (2008). 5 Fischer, D.F., Xin, Z.-q., Peters, R. ACIE 46, 7704 (2007). 6 Jautze, S., Seiler, P., Peters, R. CEJ 14, 1430 (2008). 7 Qin, Y.-c., Stivala, C.E., Zakarian, A. ACIE 46, 7466 (2007). 2

Insertion reactions. The reaction of a-diazoalkanoic esters with an aldehyde is formally a carbene insertion into the CC bond between the formyl group and the a-carbon of the aldehyde. Taking advantage of substrate control for the reaction, esteriﬁcation of the a-diazoalkanoic acid with an appropriate chiral alcohol provides the required substrate for conversion into the desired product.1

O RCHO

+

Ar

TfOH

O N2

PhMe –78°

R

CHO

Ar

COO-Men(Ph)

Ph

The most general method for preparation of chiral a-substituted esters is based on the insertion reaction that can be intimately inﬂuenced by a chiral additive. Ligands for Cu

156

Chiral auxiliaries and catalysts

salts are good candidates because decomposition of diazoalkanes (including a-diazoalkanoic esters) is known to be catalyzed by them. BOX 190 with a spirocyclic backbone is such a representative and its participation in the carbenoid insertion into the OZH bond of alcohols,2 and the NZH bond of amines3 is now on record. Another valuable ligand to complement Cu and Ag for NZH bond insertion is 144.4

O Ph

N N

Ph

O

(190) On the other hand, insertion of an amino group into CZH bonds in benzylic and allylic positions is accomplished by Rh catalysis (e.g., 191) under oxidative conditions involving ArS(O)(NTs)NH2.5

N O

O H

O

O

Rh

Rh

(191) Redox condensation between two carbonyl groups by virtue of intramolecularity can be initiated by an azolecarbene. The more electrophilic formyl group that is attached to an aromatic ring undergoes umpolung by accepting the carbene/ylide then the adduct adds across a proximal carbonyl group. The use of a chiral carbene (e.g., 192) naturally empowers enantiomerization of the reaction.6

H

N

C6F5 N N

O

CHO O R

H

O

(192) THF 25o

OH R

O

(192) A different reaction course is followed when dicarbonyl compounds are treated with a Rh(I) salt. The acylrhodium hydride that is formed on insertion of the metal ion into the

Chiral auxiliaries and catalysts

157

formyl CZH bond acts as reducing agent for the other carbonyl group. As expected, with Rh complexed to a chiral ligand the reaction gives optically active lactones.7 O CHO O

O

RhBF4

R

R

(16A) CH2Cl2

O

O (91% ee)

1

Hashimoto, T., Naganawa, Y., Maruoka, K. JACS 130, 2434 (2008). Chen, C., Zhu, S.-F., Liu, B., Wang, L.-X., Zhon, Q.-L. JACS 129, 12616 (2007). 3 Liu, B., Zhu, S.-F., Zhang, W., Chen, C., Zhou, Q.-L. JACS 129, 5834 (2007). 4 Lee, E.C., Fu, G.-C. JACS 129, 12066 (2007). 5 Liang, C., Collet, F., Robert-Peillard, F., Mu¨ller, P., Dodd, R.H., Dauban, P. JACS 130, 343 (2008). 6 Li, Y., Feng, Z., You, S.-L. CC 2263 (2008). 7 Shen, Z., Khan, H.A., Dong, V.M. JACS 130, 2916 (2008). 2

Coupling reactions. 3-Substituted 2-methyleneindanones are obtained by a Heck reaction of o-alkenoylaryl triﬂates. The most remarkable feature of the reaction is the source of the exocyclic methylene group, it being originated from the N-methyl unit of the additive, 1,2,2,6,6-pentamethylpiperidine. Of course the chiral ligand 193 is the contributor of chirality.1 The P,N-ligand 160 derived from glucosamine binds with Pd to catalyze Heck reaction of 2,3-dihydrofuran.2 O

O PAr2 PAr2

MeO MeO

R

Pd(OAc)2 (193)

OTf

N

R

dioxane

(193) Ar = 3,5-Me 2C6H3 A pleasing result pertains to enantioselective o-arylation of one of two identical aryl substituents of 2-diarylmethylpyridines.3 Stereocontrol in the Pd insertion step is crucial and the chiral ligand (194) is the determining factor. COOH HN

R

R

O O

N

Pd(OAc)2

N Ar

*

Ag2O BQ (194) ArB(OH)2

(194)

R

R

158

Chiral auxiliaries and catalysts

The organopalladium species generated from coupling reaction of ArB(OH)2 with an allene is readily trapped by a properly distanced carbonyl group. Accordingly, 5,6-alkadienals are transformed into cis-2-(a-styryl)cyclopentanols. Adding (S)-SEGPHOS to complex the Pd salt has the desirable effect of asymmetric induction.4

C Z

R

Ar

Pd(OAc)2

R CHO

Z

(S)-SEGPHOS MeCN 25o

+ ArB(OH)2

OH

Chiral 2,2-disubstituted dihydrobenzofurans in which one of the substituents is an alkenyl group can be synthesized from 2-allylphenols. A biaryl-2,20 -bisoxazoline (195) is the chiral-enabling ligand for the Pd-catalyst.5

OMe Ph

O

N N

O

Ph MeO

(195) Petasis reaction on quinoline following an analogous course to the Reissert reaction is catalyzed by the thiourea 196, water and NaHCO3 are facilitating additives.6

CF3 S F3C

N H HO

N H N

(196) The N,N0 ZdiBoc derivative of 5,6-diazabicyclo[2.2.1]hept-2-ene undergoes arylative ring opening and NZN bond cleavage on reaction with ArB(OH)2 to produce trans2-aryl-3-cyclopentenylhydrazines. Chiral products are obtained by using a chiral

Chiral auxiliaries and catalysts

159

ligand-bound Rh catalyst.7 (Hydroarylation and NZN bond cleavage occur when heteroarylboronic acids serve as the reaction partners.)

NBoc NBoc

NHBoc N Boc

[(cod)RhOH]2

Ar

(118D)

+ ArB(OH)2

x

NBoc NBoc Ar

xAr

= 2-Py, 2-Th, . . .

H[Rh] NBoc N Boc

Z

–[Rh]

monocyclic product

Z = CH

bicyclic product

Z=N

H [Rh] Z

[Rh] H NBoc N Boc

NBoc N Boc

Z

Intramolecular hydroamination of N-benzenesulfonyl-4-alkenylamine and analogues is catalyzed by Cu(OTf)2. Oxidative cyclization involving the benzene ring is promoted by MnO2 that is added.8 When a chiral BOX ligand (ent-1B) is present amidocuprate species are formed prior to hydroamination and the transition state is regulated.

R R

H

Cu(OTf)2

H N O

ent-1B MnO2

S O

R R

N O

S O

Indolizinones are formed by combining N-(4-pentenyl) isocyanate and 1-alkynes on Rh-catalysis. Interestingly, two different types of structures arise depending on whether the alkyne is an arylethyne or alkylethyne (using slightly different TADDOL-type ligands 197 and 198). The absolute conﬁguration of the angular carbon atom also differs from one series to the other, which is apparent from the chiral version of the reaction.9

o-Chloranil

160

Ar O O Ar

Ar

Ar

N

Ar

O P NR2 O Ar

O

[(C2H4)2RhCl]2

C

(197) Ar = Ph, R = Me (198) Ar = 3,5-Me2C6H3

(197)

O

R

N

R

O

R + R = (CH2)5

R'

N

[(C2H4)2RhCl]2

R'

(198)

R

From two conjugated carbonyl compounds the cross-benzoin condensation initiated by a chiral azolecarbene (199) sets up a sequence of oxy-Cope rearrangement, aldol reaction and decarboxylation.10 R' R' H

OHC N

N N

(199)

+

R

COOMe R

COOMe

H

O

(199) 1

Minatti, A., Zheng, X., Buchwald, S.L. JOC 72, 9253 (2007). Mata, Y., Pamies, O., Dieguez, M. CEJ 13, 3296 (2007). 3 Shi, B.-F., Maugel, N., Zhang, Y.-H., Yu, J.-Q. ACIE 47, 4882 (2008). 4 Tsukamoto, H., Matsumoto, T., Kondo, Y. OL 10, 1047 (2008). 5 Wang, F., Zhang, Y.J., Yang, G., Zhang, W. TL 48, 4179 (2007). 6 Yamaoka, Y., Miyabe, H., Takemoto, Y. JACS 129, 6686 (2007). 7 Menard, F., Lautens, M. ACIE 47, 2085 (2008). 8 Zeng, W., Chemler, S.R. JACS 129, 12948 (2007). 9 Lee, E.E., Rovis, T. OL 10, 1231 (2008). 10 Chiang, P.-C., Kaeobamrung, J., Bode, J.W. JACS 129, 3520 (2007). 2

o-Chloranil. Thiobenzylation. Benzyl sulﬁdes are dehydrogenated to give benzalsulfonium salts on heating with o-chloranil at 808. These can be used to react with b-keto esters. If a larger excess of o-chloranil is present (3 equiv.) the initial products are converted into the benzylidene derivatives.1

Chloro(1,5-cyclooctadiene)pentamethylcyclopentadienylruthenium(I)

O

O COOEt

Ph + Ph

o-chloranil

SMe

Ph

80o

O COOEt

Ph

161

COOEt

Ph o-chloranil

SMe

Ph

1

Li, Z., Li, H., Guo, X., Cao, L., Yu, R., Li, H., Pan, S. OL 10, 803 (2008).

1-Chlorobenzotriazole. Sulfonyl azides. A method for the preparation of sulfonyl azides starts from reaction of organometallic reagents with SO2, followed by treatment with 1-chlorobenzotriazole. The sulfonyltriazoles are very reactive toward NaN3.1 1

Katritzky, A., Widyan, K., Gyanda, K. S 1201 (2008).

Chloro(1,5-cyclooctadiene)pentamethylcyclopentadienylruthenium(I). Cycloaddition. The [2þ2þ2]cycloaddition of a diyne with an alkyne, catalyzed by the title complex, is adaptable to a synthesis of cannabinol.1 SiMe3

SiMe3

OMe OMe

Cp*Ru(cod)Cl

+ O

R

PhMe w

Me3Si

O R = n-C5H11

R

88%

Another type of useful ring closure assembles two double bonds and a triple bond.2

H

H

Cp*Ru(cod)Cl

Z

Z X

X X = O, Z = NTs 95% X = O, Z = NBn 77%

Reductive homologation and cyclopropanation are made to 1,6-enynes in their exposure to Me3SiCHN2 and Cp Ru(cod)Cl.3

162

Chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium(I)

SiMe3

TsN

H

Cp*Ru(cod)Cl

TsN

Et2O

H

+ Me3SiCHN2

86%

[Ru]

Si

Si

Si

TsN

TsN

[Ru]

TsN

[Ru]

1

Teske, J.A., Deiters, A. OL 10, 2195 (2008). Tanaka, D., Sato, Y., Mori, M. JACS 129, 7730 (2007). 3 Monnier, F., Vovard-Le Bray, C., Castillo, D., Aubert, V., Derien, S., Dixneuf, P.H., Toupet, L., Ienco, A., Mealli, C. JACS 129, 6037 (2007). 2

Chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium(I). Cycloaddition. 7-Azabenzonorbornenes undergo [3þ2]cycloaddition with alkynes, while heating with CpRuCl(PPh3)2 to form benzindoles.1 R R CpRu(PPh3)2Cl

N

Boc +

BocN

MeI dioxane 90o

1

Tenaglia, A., Marc, S. JOC 73, 1397 (2008).

1-Chloromethyl-4-ﬂuoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetraﬂuoroborate), Selectﬂuorw. Fluorohydroxylation. Allenes are functionalized by treatment with Selectﬂuorw in aq. MeCN (1 :10) at room temperature. For 1,2-alkadienes the addition yields 2-ﬂuoro-1alken-3-ols.1 Cl N 2BF4

Selectfluor

C

N F

Ar

R

Ar

MeCN-H2O (10 : 1)

Selectfluor 1

Zhou, C., Li, J., Lu¨, B., Fu, C., Ma, S. OL 10, 581 (2008).

HO F

R

Chlorotris(triphenylphosphine)cobalt(I)

163

m-Chloroperoxybenzoic acid, MCPBA. Oxidation. MCPBA is useful for oxidation of a-dithiolactones to give 1,2-dithietan3-one 1-oxides.1 R

S S

R

R

O S

MCPBA CH2Cl2

O

S R O

Hypervalent iodine reagents. Co-oxidation of electron-rich iodoarenes and iodine leads to diaryliodonium species which are conveniently isolated as tosylate or triﬂate salts.2 For access to an unsymmetrical diaryliondium salt the oxidation is carried out with a mixture of a ArI and Ar 0 B(OH)2, in the presence of BF3 . OEt2 (to form a tetraﬂuoroborate salt) at room temperature.3 A hypervalent iodine species to initiate spirolactamization of 3-( p-anisyl)propanamides is created from p-tolyl iodide (catalytic) and MCPBA (stoichiometric) in triﬂuoroethanol.4 1

Shigetomi, T., Okuma, K., Yokomori, Y. TL 49, 36 (2008). Zhu, M., Jalalian, N., Olofsson, B. SL 592 (2008). 3 Bielawski, M., Aili, D., Olofsson, B. JOC 73, 4602 (2008). 4 Dohi, T., Maruyama, A., Minamitsuji, Y., Takenaga, N., Kita, Y. CC 1224 (2007). 2

N-Chlorosuccinimide. b-Chlorohydrins. Alkenes are transformed into b-chlorohydrins by NBS in an aqueous solution, with thiourea as catalyst.1 When the reaction is carried out in ROH b-chloroalkyl ethers are obtained.2 Chlorination. Ketones are chlorinated (at an a-position) by NCS in MeOH, also in the presence of thiourea.3 1

Bentley, P.A., Mei, Y., Du, J. TL 49, 1425 (2008). Bentley, P.A., Mei, Y., Du, J. TL 49, 2653 (2008). 3 Mei, Y., Bentley, P.A., Du, J. TL 49, 3802 (2008). 2

Chlorotris(triphenylphosphine)cobalt(I). Coupling reactions.1 Highly functionalized tertiary benzylic bromides are reductively coupled by (Ph3P)3CoCl. MeOOC HPhSO2 N N MeOOC

Br COOMe N N PhSO2H COOMe

(Ph3P)3CoCl

COOMe N N PhSO2H COOMe 60%

1

Movssaghi, M., Schmidt, M.A. ACIE 46, 3725 (2007).

164

Chlorotris(triphenylphosphine)rhodium(I)

Chlorotris(triphenylphosphine)rhodium(I). Triﬂuoromethylation. Zinc enolates generated from enol silyl ethers on treatment with Et2Zn react with CF3I in the presence of (Ph3P)3RhCl to provide a-triﬂuoromethylated ketones.1 Reformatsky reaction. Reformatsky reagents are known to react with imines to afford b-lactams. The reaction can be applied to the synthesis of a,a-diﬂuoro-b-lactams, and even chiral products.2

O F F

O +

O

NR'

F

Et2Zn

R

Br

NR'

(Ph3P)3RhCl

R

F

Reductive acylation. Transmetallation occurs when Et2Zn is mixed with (Ph3P)3RhCl. The ensuing [Rh]-Et species loses ethylene rapidly and is thereby converted into a hydridorhodium compound. Enones are reduced and the Rh enolates can be acylated by RCOCl.3 The reagent that is spent is Et2Zn.

O

O

O

+ R

Cl

O

(Ph3P)3RhCl

R"

Et2Zn THF 0o

R

R" R'

R'

o-Hydroxyaryl ketones are formed in an atom-economical fashion by combining 1alkene with 2-hydroxyaraldehydes in the presence of (Ph3P)3RhCl. Formation of linear products is promoted by MeCN.4

OH

OH O

CHO

(Ph3P)3RhCl

+ R

MeCN CH2Cl2

R

Reductive silylation. Enones undergo reductive silylation to afford allyl silyl ethers by Ph2SiH2. 1,4-Reduction ending by enolate trapping is observed by using a diarylsilane in which one of the aromatic ring is o-substituted by a methoxymethyl group.5

Chlorotris(triphenylphosphine)rhodium(I)

(Ph3P)3RhCl

165

O SiHPh2

Ph2SiH2 THF

O OMe (Ph3P)3RhCl

O Si

OMe Ph H2Si

Ph

H

THF

Cycloaddition. [2þ2þ2]Cycloaddition of a diyne and an alkyne to form a product with a new benzene unit is efﬁciently catalyzed by (Ph3P)3RhCl. Signiﬁcant applications of the reaction are found in a synthesis of bruguierol-A6 and trypticenediols.7 (Ph3P)3RhCl

+

O

PhMe 80o

O HO

3 2

HO

(2- & 3-subst.) O HO bruguierol-A

R R' OH

R' +

R (Ph3P)3RhCl

R

PhMe 100o

OH R

R = H, Ph

The Rh complex also catalyzes the [4þ2]cycloaddition of conjugated oximes with alkynes that results in polysubstituted pyridines.8 R2

R6

NOH

(Ph3P)3RhCl

+ R3 R4

PhMe 130o

R5

R2

N

R3

R6 R5

R4

Rearrangement. 2-(3-Cyclopropenyl)pyridines undergo rearrangement to give indolizines under the inﬂuence of certain metal salts. When the cyclopropenyl group is

166

Chromium – carbene complexes

unsymmetrically substituted the bonding reorganization can be traced. It is noted that products generated from reactions catalyzed by (Ph3P)3RhCl and by CuI are different.9 R' (Ph3P)3RhCl

N

DMF 25o

R" R'

R"

R

N

R' CuI

R

DMF 25o

R"

N R

1

Sato, K., Yuki, T., Tarui, A., Omote, M., Kumadaki, I., Ando, A. TL 49, 3558 (2008). Tarui, A., Ozaki, D., Nakajima, N., Yokota, Y., Sokeirik, Y.S., Sato, K., Omote, M., Kumadake, I., Ando, A. TL 49, 3839 (2008). 3 Sato, K., Yamazoe, S., Yamamoto, R., Ohata, S., Tarui, A., Omote, M., Kumadake, I., Ando, A. OL 10, 2405 (2008). 4 Imai, M., Tanaka, M., Nagumo, S., Kawahara, N., Suemune, H. JOC 72, 2543 (2007). 5 Imao, D., Hayama, M., Ishikawa, K., Ohta, T., Ito, Y. CL 36, 366 (2007). 6 Ramana, C.V., Salian, S.R., Gonnade, R.G. EJOC 5483 (2007). 7 Taylor, M.S., Swager, T.M. OL 9, 3695 (2007). 8 Parthasarathy, K., Jeganmohan, M., Cheng, C.-H. OL 10, 325 (2008). 9 Chuprakov, S., Gevorgyan, V. OL 9, 4463 (2007). 2

Chromium – carbene complexes. Cycloadditions. N-Dimethylaminoisoindoles are formed when o-alkynylaraldehyde N,N-dimethylhydrazones are treated with a Fischer carbene complex. The isoindoles are trapped by an acetylenedicarboxylic ester in situ to generate naphthalene derivatives.1 SiMe3 +

Me3Si

Cr(CO)5

NNMe2

OMe

NNMe2 E

E

OMe Me3Si COOMe COOMe

Chromium – carbene complexes

167

The Do¨tz benzannulation products involving propargyloxy derivatives are liable to elimination, leading to o-quinonemethides whch can be trapped.2

(OC)5Cr

OBn

OR

OMe

RO

i-Pr2NEt

+

Cr(CO)3

PhMe

HO

Ph

Ph

R = TBS

H H

OMe

OMe

Cr(CO)3

Cr(CO)3 O

O Ph

Ph

Through initiation by another [nþ2]cycloaddition the usefulness of the Do¨tz reaction is expanded, products more varied in structural types become available.3

Ph MeO

OMe

Ph Ph R''

(OC)5M

N

O

O

O

OMe

H

R"N

R"N

R=H

R = Ph, Me R MeO MeO

M = Cr, W

OTMS

O H

M = Cr 81% M = W 73%

Also the intramolecular cycloaddition to form macrocycle en route to arnebinol4 and phomactin-B2 5 are remarkably efﬁcient.

168

Chromium – carbene complexes

Cr(CO)5 Me3Si

Cr(CO)5

O

AcBr;

Me3Si

ONMe4

ROH

PhMe 60o; TFA

O

OH arnebinol O

OTIPS

OTIPS MeO THF 60o

(OC)5Cr

MeO

60–66%

O

O OH

phomactin-B2

Conjugated Fischer carbene complexes undergo [3þ2]cycloaddition to afford 2-cyclopentenones.6 The reaction is carried out in the presence of Ni(cod)2. MeO

R"

Cr(CO)5 + R

O Ni(cod)2;

R"

SiO2

R'

R

R'

40–75%

Cinchona alkaloid derivatives

169

Employing a [4þ1]cycloaddition that unites a conjugated carbonyl unit with the carbenoid center of a Cr-complex paves way to a novel approach to furans.7

MeO MeO

Cr(CO)5 + Ar

O

R

O

R

THF 120o

Ar

1

Duan, S., Sinha-Mahapatra, D.K., Herndon, J.W. OL 10, 1541 (2008). Korthals, K.A., Wulff, W.D. JACS 130, 2898 (2008). 3 Barluenga, J., Andina, F., Aznar, F., Valdes, C. OL 9, 4143 (2007). 4 Watanabe, M., Tanaka, K., Saikawa, Y., Nakata, M. TL 48, 203 (2007). 5 Huang, J., Wu, C., Wulff, W.D. JACS 129, 13366 (2007). 6 Barluenga, J., Barrio, P., Riesgo, L., Lopez, L.A., Tomas, M. JACS 129, 14422 (2007). 7 Barlueuga, J., Faulo, H., Lopez, S., Florez, J. ACIE 46, 4136 (2007). 2

Chromium(II) chloride. Addition. Secondary and tertiary alkyl halides react with ArCHO under the inﬂuence of CrCl2 – LiI and a catalytic amount of vitamin-B12 in DMF. It is likely the reaction proceeds via coupling of alkyl and ketyl radicals.1 Alkenylchromium reagents are obtained from 1,1,1-trichloroalkanes by treatment with CrCl2 – LiI in THF.2 These reagents add to aldehydes to form allylic alcohols. From 1,1,1-trichloroethanol the primary reaction products are further dehydrated to give conjugated aldehydes. a,a,a-Trichloromethylarenes afford diarylethynes. Cyclopropanation.3 The double bond of acrylamides is cyclopropanated by the combination of CrCl2 and ClCH2I. 1

Wessjohann, L.A., Schmidt, G., Schrekker, H.S. T 64, 2134 (2008). Bejot, R., He, A., Falck, J.R., Mioskowski, C. ACIE 46, 1719 (2007) 3 Concellon, J.M., Rodriguez-Solla, H., Mejica, C., Blanco, E.G. OL 9, 2981 (2007). 2

Cinchona alkaloid derivatives. Desymmetrization reactions. Cinchona alkaloids are relative abundant, morevover, the fact that the two series of quinine/cinchonidine and quinidine/cinchonine often can catalyze reactions in the opposite chirality sense makes the use of them and their derivatives very valuable in creating new stereogenic centers from prochiral substances, in one or both optical series.

170

Cinchona alkaloid derivatives

Formation of chiral a-amino acids from aminomalonic acids via decarboxylative protonation is readily accomplished in the presence of thiourea 1 (ex quinidine).1 The diastereomeric 2 (ex quinine) has been employed to generate monomethyl esters in chiral form by methanolysis meso-cyclic anhydrides.2

N

H N

H N

F3C

H

S CF3

H N

F3C OMe

H N

H N

S CF3

N

(1)

OMe N

(2)

Electrophilic reactions. Asymmetric bromination of alkanoyl chlorides with 1,1,3,6tetrabromo-1,2-dihydronaphthalen-2-one is catalyzed by the quinine – derived 3, it affords (S)-a-bromoalkanoic esters on alcoholysis of the products.3 Quaternization of quinine with 9-chloromethylanthracene gives a salt that is useful for catalyzing asymmetric C-3 hydroxylation of N-protected oxindoles. The quaternary ammonium salt plays a dual role in that it also serves as a phase-transfer catalyst.4

H

H N Boc

N

O O

OMe N

(3)

Reactions of carbonyl compounds and imines. The salt 4 obtained from reaction of cinchonine with m-xylylene dibromide is shown to promote enantioselective transfer of the triﬂuoromethyl group from Me3SiCF3 to aryl ketones.5 Also obtained from quinidine the salt containing a triﬂuorobenzyl group (5) promotes the condensation of chloromethyl phenyl sulfones with ArCHO to give benzenesulfonyl epoxides.6

Cinchona alkaloid derivatives

Ar N

HO

171

R

2Br Me3SiCF3 Me4NF

(4)

N N

N

OH

HO

CF3

Ar

R

(4) ArCHO + N

HO

Cl

SO2Ph

Br RbOH PhMe

F MeO F

(5)

O

F Ar

N

SO2Ph

(5) N-(a-Benzenesulfonylalkyl)carbamates are adequate surrogates of imines. Being adducts of imines, the (S)-1-ﬂuoro-2-alkylamine derivatives can be prepared from the carbamates with bis(benzenesulfonyl)ﬂuoromethane in the presence of quinidine benzochloride and CsOH, followed by twofold desulfonylation with Mg in MeOH.7 Strecker reaction catalyzed by (i-PrO)4Ti whereby tosylimines accept Me3SiCN enantioselectively is achieved by modifying the environment surrounding the metal center by alkoxy group exchange with 3,30 -di(b-naphthyl)-2,20 -dihydroxybiphenyl, and further complexation with cinchonine.8 Aza-Henry reaction is rendered asymmetric by quaternary salts of Cinchona alkaloids.9 Addition reactions. Changing the 9-hydroxy group of Cinchona alkaloids to a 9-epiamino group not only is synthetically expedient, such products often show excellent catalytic activities in many asymmetric reactions. Those derived from dihydrocinchona alkaloids mediate Michael reactions to good results, including addition of indole to enones,10 and carbonyl compounds to nitroalkenes.11 Salt 4 has also been successfully employed in the alkenylation of t-butyl a-aryl-a-cyanoacetate.12 O R

Ar O

Cl

(4)

O

+ CN

base

R

O O Ar

O CN

Thiourea 2 directs entantioselective hydration of the double bond of g-hydroxypropenyl ketones by virtue of multiple H-bonding interactions.13

172

Cinchona alkaloid derivatives

R

N H

N S

N

Ar N

O

H

Ph B O HO

PhB(OH)2

O

Ph O B O

R

H R

Complementary functions of quinine and quinidine derivatives are revealed again in the Michael reaction between 2-cyano-1-indanone and a-chloroacrylonitrile, with them anyone of four possible chiral diastereomers can be prepared at will.14 O

O

CN Cl

CN Cl

O

CN

CN CN

Q-P

+ O CN Cl

Cl

QD-P

CN

Q-T

QD-T

O CN Cl CN

CN Q-P QD-P Q-T QD-T

de-O-methylquinine 9-phenanthr-9-yl ether de-O-methylquinidine 9-phenanthr-9-yl ether N-(quinin-9-yl)-N ′-[3,5-bis(trifluoromethyl)phenyl]thiourea N-(quinidin- 9-yl)-N ′-[3,5-bis(trifluoromethyl)phenyl]thiourea

A tridentate ligand is obtained from a quinine glycinate ester in which the primary amino group is further incorporated into a 3,5-di-t-butylsalicylaldimine. However, its useful scope in catalyzing enantioselective addition of Et2Zn to ketones is quite limited.15 Cycloadditions. Epoxidation of 2-methyl-1,4-naphthoquinone (vitamin-K3) by NaOCl is best catalyzed by de-O-methylquinine anthracyl-9-methochloride, according to a computer analysis.16 Epoxidation of 2-cycloalkenones by H2O2 with 9-epiamino-9deoxyquinine as catalyst shows opposite enantioselectivity as that with (R,R)-1,2diphenylethanediamine.17 The ester of quinine (5) is an excellent catalyst for b-lactone synthesis from ketene and certain aldehydes.18

Cinchona alkaloid derivatives

173

60 -Hydroxycinchonidine 9-benzoate (from quinine) also catalyzes the [3þ2]cycloaddition of a-isocyanoalkanoicesters with nitroalkenes to yield 2,3-dihydropyrrole2-carboxylic esters.19 OMe O

N O N

H

O

OBn

N N

Co

O C CH2

+

O

(5)

O O O

(5)

OBn (>99% ee)

Both 9-epiamino derivatives of 9-deoxyquinine and 9-deoxyquinidine promote exoselective Diels–Alder reaction of 3-hydroxy-2-pyrones with enones.20 Actually, great latitude exists for tuning the reaction by partial structural changes of the catalysts.21 The hetero-Diels –Alder reaction between nascent ketenes generated from crotonyl chlorides and trichloroacetaldehyde, is effected by Sn(OTf)2, and rendered asymmetric by a TMS derivative of quinidine.22 1

Amere, M., Lasne, M.-C., Rouden, J. OL 9, 2621 (2007). Peschiulli, A., Gun’ko, Y., Connon, S.J. JOC 73, 2454 (2008). 3 Dogo-Isonagie, C., Bekele, T., France, S., Wolfer, J., Weatherwax, A., Taggi, A.E., Paull, D.H., Dudding, T., Lectka, T. EJOC 1091 (2007). 4 Sano, D., Nagata, K., Itoh, T. OL 10, 1593 (2008). 5 Mizuta, S., Shibata, N., Akiti, S., Fujimoto, H., Nakamura, S., Toru, T. OL 9, 3707 (2007). 6 Ku, J.-M., Yoo, M.-S., Park, H.-g., Jew, S.-S., Jeong, B.-S. T 63, 8099 (2007). 7 Mizuta, S., Shibata, N., Goto, Y., Furukawa, T., Nakamura, S., Toru, T. JACS 129, 6395 (2007). 8 Wang, J., Hu, X., Jiang, J., Gou, S., Huang, X., Liu, X., Feng, X. ACIE 46, 8468 (2007). 9 Gomez-Bengoa, E., Linden, A., Lopez, R., Mugica-Mendiola, I., Oiarbide, M., Palomo, C. JACS 130, 7955 (2008). 10 Bartoli, G., Bosco, M., Carlone, A., Pesciaioli, F., Sambri, L., Melchiorre, P. OL 9, 1403 (2007). 11 McCooey, S.H., Connon, S.J. OL 9, 599 (2007). 12 Bell, M., Poulsen, T.B., Jorgensen, K.A. JOC 72, 3053 (2007). 13 Li, D.R., Murugan, A., Falck, J.R. JACS 130, 46 (2008). 14 Wang, B., Wu, F., Wang, Y., Liu, X., Deng, L. JACS 129, 768 (2007). 15 Casarotto, V., Li, Z., Boucau, J., Lin, Y.-M. TL 48, 5561 (2007). 16 Berkessel, A., Guixa, M., Schmidt, F., Neudo¨rﬂ, J.M., Lex, J. CEJ 13, 4483 (2007). 17 Wang, X., Reisinger, C.M., List, B. JACS 130, 6070 (2008). 18 Lin, Y.-M., Boucau, J., Li, Z., Casarotto, V., Lin, J., Nguyen, A.N., Ehrmantraut, J. OL 9, 567 (2007). 19 Guo, C., Xue, M.-X., Zhu, M.-K., Gong, L.-Z. ACIE 47, 3414 (2008). 2

174

Cobalt

20

Singh, R.P., Bartelson, K., Wang, Y., Su, H., Lu, X., Deng, L. JACS 130, 2422 (2008). Wang, Y., Li, H., Wang, Y.-Q., Liu, Y., Foxman, B.M., Deng, L. JACS 129, 6364 (2007). 22 Tiseni, P., Peters, R. ACIE 46, 5325 (2007). 21

Cobalt. Coupling reactions. Hollow nanospheres of cobalt can substitute for Pd species in Sonogashira coupling. The catalyst system still contains CuI, Ph3P, and K2CO3.1 For conducting the Heck reaction with acrylic esters, no ligand is needed.2 1

Feng, L., Liu, F., Sun, P., Bao, J. SL 1415 (2008). Zhou, P., Li, Y., Sun, P., Bao, J. CC 1418 (2007).

2

Cobalt– rhodium. Carbamoylation. Nanoparticles of the Co2Rh2 bimetallic species catalyze cis addition of H/CONR2 to alkynes, where the addend groups come from R2NH and CO.1 Cycloaddition. A synthesis of bicyclic dienones by the Pauson –Khand reaction of an allene/yne is based on catalysis by Co2Rh2.2 Two molecules of an allene combine with CO to form 4-alkylidene-2-cyclopentenones.3 O C

2

+ CO

Rh2Co2 PhMe

R

R

R

1

Park, J.H., Kim, S.Y., Kim, S.M., Chung, Y.K. OL 9, 2465 (2007). Park, J.H., Kim, S.Y., Kim, S.M., Lee, S.I., Chung, Y.K. SL 453 (2007). 3 Park, J.H., Kim, E., Kim, H.-.M., Choi, S.Y., Chung, Y.K. CC 2388 (2008). 2

Cobalt(II) acetylacetonate. Aldol reaction. Reductive aldol reaction of conjugated amides, according to an intramolecular version as previously reported, is fully applicable to the preparation of syn-3-hydroxyalkanamides.1 R" OH O

R'2N O

R" O

+

Co(acac)2 Et2Zn

R'" R 1

Lumby, R.J.R., Joensuu, P.M., Lam, H.W. OL 9, 4367 (2007).

R'"

NR'2 R

Cobalt(II) chloride

175

Cobalt(II) bromide. Biaryls. Coupling of two ArX is mediated by Mn and catalyzed by CoBr2 –Ph3P in DMF and pyridine (6 : 1). There is no need to prepare ArM.1 Cyclotrimerization. Alkynes (e.g., PhCCH) are trimerized on exposure to CoBr2 along with Zn-ZnI2. Isomer ratio changes with respect to ligands.2

Ph Ph

Ph

CoBr2

3

Ph +

Zn, ZnI2 25o

Ph

ligand: PhSCH 2CH2SPh / CH2Cl2

Ph 2.9

CyN=C=CNCy / MeCN

Ph :

1

1

: 19.2

1

Amatore, M., Gosmini, C. ACIE 47, 2089 (2008). Hilt, G., Hengst, C., Hess, W. EJOC 2293 (2008).

2

Cobalt(II) chloride. Cyclopropanation. A bimetallic catalyst composing of CoCl2, AgOAc and the ligand 1 is used for cyclopropanation of styrenes. Intramolecular cyclopropanation leads to cyclopropanolactones.1

Ph

Ph

N2

Ph

O Ph

N

Ph N H

O (1)

AgOAc

N O

O

(1)

CoCl2

H Ph

H H

Cross-coupling. Radicals are generated from 2-vinylsiloxy-1-iodoalkanes in the presence of an azolecarbene-complexed CoCl2. Rapid transfer of the radical site to the carbon b to the silicon on ring closure precedes coupling with a Grignard reagent that is added. The method can be used to build a carbon chain containing a 1,3-diol unit.2

176

Cobalt(II) iodide/phosphine – zinc

R

O

Si

O

R CoCl2

Si

I N

+

Ph Si MgCl

..

N

dioxane

Si Ph 25o

.1

Langlotz, B.K., Wakepohl, H., Gade, L.H. ACIE 47, 4670 (2008). Someya, H., Ohmiya, H., Yorimitsu, H., Oshima, K. T 63, 8609 (2007).

2

Cobalt(II) iodide/phosphine – zinc. Cycloaddition. 3-Methylenecyclopentanols are assembled from conjugated carbonyl compounds and allenes.1

R'

R C

+

HO

(dppe)CoI2

R

R'

Zn, ZnI2

O

MeCN, H2O 80o

O COOMe O

(dppe)CoI2

+ O C

Zn, ZnI2 MeCN, H2O 80o

H 51%

Aryl sulﬁdes.

Arylation of thiols is mediated by the title reagent mix.2

1

Chang, H.-T., Jayanth, T.T., Cheng, C.-H. JACS 129, 4166 (2007). Wong, Y.-C., Jayanth, T.T., Cheng, C.-H. OL 8, 5613 (2006).

2

Copper. Coupling reactions. Nanosized copper is a good catalyst for Ullmann ether synthesis, using Cs2CO3 as base in MeCN at 50–608.1 Carbon-supported copper in the presence of 1,10-phenanthroline shows similar activities with the aid of microwave irradiation.2 N-Arylation of N-heterocycles (benzimidazole, triazole, . . .) by ArSi(OR)3 is mediated by Cu– FeCl3 and TBAF in the air.3 Sonogashira coupling is conducted more conveniently and less expensively with Cu/Al2O3, without the need of palladium and ligand.4 Replacement of a vinylic iodide

Copper(II) acetate

177

(including 5-iodouracil) by a triﬂuoromethyl group can be carried out by a copper-catalyzed reaction with (CF3)2Hg in DMA at 1408.5 Glaser coupling of 1-alkynes followed by [3þ2]cycloaddition with organoazides affords bi-5,50 -triazolyls. Achieved in one step with Cu and CuSO4 in the air, the reaction is particularly favored by adding Na2CO3.6 1

Kidwai, M., Mishra, N.K., Bansal, V., Kumar, A., Mozumdar, S. TL 48, 8883 (2007). Lipshutz, B.H., Unger, J.B., Taft, B.R. OL 9, 1089 (2007). 3 Song, R.-J., Deng, C.-L., Xie, Y.-X., Li, J.-H. TL 48, 7845 (2007). 4 Bifﬁs, A., Scattolin, E., Ravasio, N., Zaccheria, F. TL 48, 8761 (2007). 5 Nowak, I., Robins, M.J. JOC 72, 2678 (2007). 6 Angell, Y., Burgers, K. ACIE 46, 3649 (2007). 2

Copper(II) acetate. Coupling reactions. Glaser coupling of alkynyltriﬂuoroborate salts using Cu(OAc)2 in DMSO at 608 gives conjugated diynes.1 Aryl sulfones are synthesized from RSO2Na and Ar 0 B(OH)2 under oxidative conditions (DMSO, O2). Two similar procedures, both using Cu(OAc)2 as catalyst but different N-heterocycle addends, have been established.2,3 N-Cyclopropylation of indole is accomplished, also by following a similar recipe, with the necessary changing the coupling partner to cyclopropylboronic acid.4 Cyclization of N-arylamidines to afford benzimidazoles involves activation of the o-CZH bond in a process realized by the action of Cu(OAc)2 in DMSO (containing 2.5 equiv. HOAc) under O2 at 1008.5 H N

H N

Cu(OAc)2

R NH

R

HOAc/DMSO

N

O2/100°

Heterocycles. Heating a mixture of a nitroalkane and styrene with Cu(OAc)2 and N-methylpiperidine in CHCl3 at 608 leads to 5-phenylisoxazolines, no dehydrating agent is needed.6 A method for pyridine synthesis7 from conjugated oxime esters and alkenylboronic acids perhaps involves CZN coupling, electrocyclization and dehydrogenation in the air.

N Ar

Ar'

N

Cu(OAc)2

OCOC6F5 + (HO)2B

R

air, DMF 50°– 90°

Ar

R Ar'

Nitroaldol reaction. When the stereocontrolled condensation is conducted in the presence of Cu(OAc)2, which is complexed to the polymer-linked diamine 1, the catalyst is readily recovered.8

178

Copper(II) bis(hexaﬂuoroacetylacetonate)

S S NH NH S

O

(1) 1

Paixao, M.W., Weber, M., Braga, A.L., de Azeredo, J.B., Deobald, A.M., Stefani, H.A. TL 49, 2366 (2008). 2 Kar, A., Sayyed, I.A., Lo, W.F., Kaiser, H.M., Beller, M., Tse, M.K. OL 9, 3405 (2007). 3 Huang, F., Batey, R.A. T 63, 7667 (2007). 4 Tsuritani, T., Strotman, N.A., Yamamoto, Y., Kawasaki, M., Yasuda, N., Mase, T. OL 10, 1653 (2008). 5 Brasche, G., Buchwald, S.L. ACIE 47, 1932 (2008). 6 Cecchi, L., De Sarlo, F., Machetti, F. SL 2451 (2007). 7 Liu, S., Liebeskind, L.S. JACS 130, 6918 (2008). 8 Bandini, M., Benaglia, M., Sinisi, R., Tommasi, S., Umani-Ronchi, A. OL 9, 2151 (2007).

Copper(II) bis(hexaﬂuoroacetylacetonate). Isomerization. 2-Alkenyloxiranes give 2,5-dihydrofurans on heating with the Cu(II) complex. With the simple acetylacetonate larger amounts of unsaturated aldehydes (the other type of isomerization products) are obtained.

O

O

Cu(hfacac)2 PhMe 150°

R

Cu(hfacac)2

R

O

PhMe 150°

R

1

Batory, L.A., McInnis, C.E., Njardarson, J.T. JACS 128, 16054 (2006).

Copper(I) bromide. Oxidative coupling. With a mixture of CuBr – 1,10-phenanthroline and palladium(II) triﬂuoroacetylacetonate, and also tri(o-tolyl)phosphine, the coupling of aryl bromides and potassium 2-oxoalkanoates with loss of CO2 provides aryl ketones.1 N-Methylamines are oxidatively activated by CuBr and NBS. They are transformed into propargylic amines on reaction with 1-alkynes that are placed in the reaction media.2

Copper(II) bromide

R R

R'

CuBr – NBS

+

N

R"

179

R' N

MeCN 80o

R"

Ullmann coupling of aryl halides possessing a coordinative functionality in the orthoposition are very favorable because the arylcopper intermediates are stabilized. An oxygen atom from an acetal unit shows the beneﬁcial effect, enabling the simpliﬁcation of synthetic processes (by not having to employ the thioacetal).3

NCy MeO + MeO

Br

H

MeO

O

BuLi; CuBr · P(OEt)3;

Br OMe

O

O

O

MeO

10% HOAc

OBn

O

MeO OBn

Reactions involving b-diketones. Diphenylation of b-diketones occurs when they are heated with anthranilic acid in the presence of catalytic amounts of CuBr and Cl3CCOOH (5 mol% each) in 1,2-dichloroethane at 608.4 Aldehydes are oxidized in situ by CuBr –t-BuOOH to supply O-acylating agents for b-diketones.5 1

Goossen, L.J., Rudolphi, F., Oppel, C., Rodriguez, N. ACIE 47, 3043 (2008). Niu, M., Yin, Z., Fu, H., Jiang, Y., Zhao, Y. JOC 73, 3961 (2008). 3 Broady, S.D., Golden, M.D., Leonard, J., Muir, J.C., Maudet, M. TL 48, 4627 (2007). 4 Yang, Y.-Y., Shou, W.-G., Wang, Y.-G. TL 48 8163 (2007). 5 Yoo, W.-J., Li, C.-J. JOC 71, 6266 (2006). 2

Copper(II) bromide. Dehydrogenation. Aromatization of 3,4-diaryl-2,5-dihydro derivatives of furan, thiophene, and N-arylpyrrole is accomplished in 80 –91% yield by heating with CuBr2 (3 equiv.) in EtOAc.1 Substitution. Propargylic alcohols are readily transformed into mixed ethers and sulﬁdes when they are treated with ROH and RSH in the presence of CuBr2 in MeNO2 at room temperature.2 1

Dang, Y., Chen, Y. EJOC 5661 (2007). Hui, H., Zhao, Q., Yang, M., She, D., Chen, M., Huang, G. S 191 (2008).

2

180

Copper(I) chloride

Copper(I) chloride. Additions. Hydroboration of conjugated esters and nitriles with (bispinacolato)diboron in MeOH, promoted by CuCl in the presence of t-BuONa, proceeds in good yields.1 Under microwave irradiation an azolecarbene-complexed CuCl induces cyclization of o-allylaryl trichloroacetates via a free radical process. The initial adducts undergo decarboxylation and dehydrochlorination that lead to aromatization.2,3 Cl CuCl

O

Cl

azolecarbene w

O

O

CCl3

Cl

Cl

O

Cycloadditions. N,N0 -Di-t-butylthiadiaziridine S,S-dioxide reacts with activated terminal alkenes in the presence of CuCl and Bu3P to give ﬁve-membered heterocycles.4 This reaction effectively performs the critical step of vic-diamination of the alkenes. Analogously, cyclic N-cyanoguanidine 1 also undergoes cycloaddition to alkenes, with Ph3P to stabilize CuCl.5 NCN

NCN CuCl

+ N N

R

N

Ph3P

N R

1,2,3-Triazole synthesis is also catalyzed by CuCl trapped in zeolite. No ligand for the metal salt is required.6 Coupling reactions. Diaryl ethers are formed (Ullmann synthesis) by treatment of the reactants (ArOH and Ar 0 Br) with CuCl and 1-butylimidazole in toluene.7 Diaryl sulﬁdes can be prepared similarly, with some variation of the reaction conditions (in water, presence of 1,2-diaminocyclohexane).8 A three-component coupling to construct 2-(a-iminyl)pyrroles is regioselective. The reaction is suitable for the preparation of libraries of products by using different 1-alkynes.9

N H R

N

CuCl

+ Ts-N3

Et3N

LnCu C N R

NTs

N H SO2Ar

R

A new protocol for the condensation of aldehydes (except fomaldehyde), amines, and alkynes to give propargylic amines entails the employment of CuCl and Cu(OTf)2 (5 mol% each) to create a cooperative catalyst system and the use of trimethylsilylalkynes.10

Copper(I) cyanide

181

1

Lee, J.-E., Yun, J. ACIE 47, 145 (2008). Bull, J.A., Hutchings, M.G., Quayle, P. ACIE 46, 1869 (2007). 3 Bull, J.A., Hutchings, M.G., Lujan, C., Quayle, P. TL 49, 1352 (2008). 4 Zhao, B., Yuan, W., Du, H., Shi, Y. OL 9, 4943 (2007). 5 Zhao, B., Du, H., Shi, Y. OL 10, 1087 (2008). 6 Chassaing, S., Kumarraja, M., Sido, A.S.S., Pale, P., Sommer, J. OL 9, 883 (2007). 7 Schareina, T., Zapf, A., Cotte, A., Mu¨ller, N., Beller, M. TL 49, 1851 (2008). 8 Carril, M., SanMartin, R., Dominguez, E., Tellitu, I. CEJ 13, 5100 (2007). 9 Cho, S.H., Chang, S. ACIE 47, 2836 (2008). 10 Sakai, N., Uchida, N., Konakahara, T. SL 1515 (2008). 2

Copper(II) chloride. Rearrangement.1 Azines are produced from [3,3]sigmatropic rearrangement of N 0 -Boc N 0 -allylhydrazones. In the presence of CuCl2 and i-Pr2NEt oxidative chlorination also occurs.

N

Boc N

Cl CuCl2 i-Pr2NEt MeCN

62%

Triazole synthesis.2 A heterogeneous catalyst for the click reaction is formed by treating CuCl2 with (s-BuO)3Al. 1

Mundal, D.A., Lee, J.J., Thomson, R.J. JACS 130, 1148 (2008). Park, I.S., Kwon, M.S., Kim, Y., Lee, J.S., Park, J. OL 10, 497 (2008).

2

Copper(I) cyanide. Cycloaddition. Diazoacetic esters and alkyl lithiopropynoates form pyrazoledicarboxylic esters in THF by a formal [3þ2]cycloaddition. It is catalyzed by CuCN . 6LiCl.1

BnOOC

BnOOC

N2

CuCN · 6LiCl

+ Li

H N

THF

COOEt

COOEt 82%

1

Qi, X., Ready, J.M. ACIE 46, 3242 (2007).

N

182

Copper(II) 2-ethylhexanoate

Copper(II) 2-ethylhexanoate. Cyclization. Intramolecular oxidative addition of an amidic nitrogen atom and a sp 2-hybridized carbon to a double bond is effected by the Cu(I) carboxylate.1 This type of reaction has been accomplished by Cu(OAc)2 on unsaturated sulfonamides. O

COO)2Cu

N H

O N

Cs2CO3 120°–140°

74% O

O COO)2Cu

NH

N Cs2CO3 120°–140°

72% 1

Fuller, P.H., Chemler, S.R. OL 9, 5477 (2007).

Copper(II) hexaﬂuoroacetylacetonate. Cyclization.1 Like many other copper salts the title compound catalyzes decomposition of diazoketones. A case of heteroatom trapping followed by a [2,3]Wittig rearrangement to generate an 11-oxabicyclo[5.3.1]undecenone serves to illustrate the synthetic potentials of the process. AcO H

F3C

H O

O

F3C

N2

O Cu O 2

AcO H

H O

OTIPS

OTIPS O

(E + Z )

AcO H O

O 1

H

OTIPS

Clark, J.S., Baxter, C.A., Dossetter, A.G., Poigny, S., Castro, J.L., Whittingham, W.G. JOC 73, 1040 (2008).

Copper(I) iodide

183

Copper(I) iodide. Baeyer– Villiger oxidation. The BuO-Cu(III)-NO species formed on heating CuI with Bu4NNO2 in o-xylene at 1508 converts aryl isopropyl ketones and aryl triﬂuoromethyl ketones to butyl esters. However, the scope of this reaction is limited, ethyl and methyl ketones give low yields of the corresponding esters and phenyl and t-butyl ketones are not oxidized at all under such conditions.1 Deoxygenation. Amine oxides are deoxygenated by heating with CuI and i-Pr2NEt in THF.2 Coupling reactions. Ether synthesis from ArX originated from Ullmann. Reaction involving mediation by CuI is improved in the presence of 3,4,7,8-tetramethyl-1,10phenanthroline3 or N,N-dimethylglycine.4 Diaryl ethers can be synthesized by heating ArOH and Ar0 X with ligand-free CuX (X ¼ I, Br, Cl) and Cs2CO3 in NMP.5 Another protocol sparing ligands is compensated by Bu4NBr.6 b-Styryl aryl ethers, sulﬁdes, and amines are similarly prepared from b-styryl bromide. One interesting aspect of the coupling method is the employment of ethyl 2-oxocyclohexanecarboxylate as the ligand for CuI.7 9-Azajulolidine is a more general and powerful ligand for coupling reactions leading to diaryl ethers, sulﬁdes, and amines.8 Heteroaryl cyanides prepared from bromides and K4Fe(CN)6 is accomplished in the presence of CuI and an N-alkylimidazole.9 A highly efﬁcient cyclization of 2-chloro-4-sulfonamino-1-alkenes to 2-methyleneazetidines provides an avenue to b-lactams, e.g., on ozonolysis of the products.10 Pertinent to cyclization of bromoallyl bromohomoallyl carbinols is the chemo/regioselectivity. It is actually dependent on the nature of the promoter, CuI or Pd(OAc)2.11 O

CuI

Br Bn

Cs2CO3 MeCN

OH

Bn Br

Br

Br

Pd(OAc)2 BINAP DME

O Bn

In hetero-Ullmann coupling, i.e., arylation of phenols, thiols, and amides with ArI, a useful ligand for the CuI mediator is 1,1,1-tris(hydroxymethyl)ethane.12 Further extension of the Ullmann reaction to the preparation of aryl cyanides from ArBr and K4Fe(CN)6 is probably quite routine.13 With the additive 2-oxazolidinone in DMSO to assist CuI at 1208, N-arylation of amides (lactams) is readily performed.14 A more commonly used ligand is 1,10-phenanthroline, as it is applied also to form N-(aryl)alkoxyamines from RNHOR0 .15 In N-arylation of N-heterocycles (indole, pyrrole, imidazole, pyrazole, . . .), 1,3-di(2-pyridyl)-1,3-propanedione appears to be a useful ligand for CuI.16

184

Copper(I) iodide

It is fortunate that arylation of aminoalcohols at either the nitrogen or the oxygen atom can be performed at will, by changing the ligand.17

NHAr

NH2 Br

I

NH2

CuI

+

+

Cs2CO3 ligand

OH

OH O

ligand:

OAr Ar = 3-BrC6H4

97% (>50 : 1)

O

86% (1 : >20)

N N

As ammonia can hardly be used in coupling with ArX, access to ArNH2 needs ﬁnding a surrogate with good selectivity and CF3CONH2 fulﬁlls the requirement.18 The coupling products undergo methanolysis to deliver arylamines. Two methods have been developed recently for pyrrole synthesis: a twofold coupling reaction of (Z,Z)-1,4-dihalo-1,3-dienes (bromides and iodides) with BocNH2,19 and stepwise coupling of alkenyl iodides with N,N0 -diBoc hydrazine.20

I I

CuI

+ Boc-NH2 N H

N Boc

H N

99% R2

I

CuI

Boc N NHBoc

R2

Cs2CO3

R3

DMF 80o

+ NHBoc NHBoc

R3 I R5 R4

R2 R3

Boc

R2

N R5 R4

xylene

CuI

Boc N NBoc

R3

R5 R4

N N

Cs2CO3

Copper(I) iodide

185

Arylation of malonic esters at room temperature occurs when the reactants are treated with CuI, picolinic acid and Cs2CO3.21 And despite the general inertness of arenes, benzoxazole22 and pentaﬂuorobenzene23 are found to react with ArX. Amidine synthesis. Alkynes, amines, and sulfonylazides (or phosphoryl azides) are combined to generate amidines. The alkynes and/or the amines can be functionalized, and their use leads to amidines containing an a-amino group or a phosphoranylalkyl group, when starting from ynamides24 and imidophosphoranes,25 respectively.

R' +

R2N

HN

CuI

R'

NR'2

R2N

NSO2Ar

N3 SO2Ar

R

N3 SO2Ar

NSO2Ar

CuI

+ Ph3P NR'

Et3N CH2Cl2

R

NHR' PPh3

Heterocycles. 3-Aminomethylisoquinolines are obtained from o-ethynylaraldehydes by treatment with paraformaldehyde and amines, then t-BuNH2.26 Aminomethylation of the alkyne unit is followed by Schiff reaction and cyclization. Cyclic amidines that serve as precursors of oxindoles are assembled from o-ethynylarylamines and sulfonyl azides.27

+ R'SO2N3

CuI

NSO2R' N R

N

NHR

Catalyzed by CuI, N,N0 -ditosyl-1,2-ethanediamine and N-tosylaminoethanol add to bromoalkynes to furnish derivatives of tetrahydropyrazine and dehydromorpholine, respectively.28 The sulfonyl group appears to place an important role in directing the complexation of the copper atom to the triple bond.

R

CuI

+ HO

NHTs

H N N H K3PO4, DMF

R O

NTs

R = C6H13 71%

186

Copper(I) iodide

A previous observation concerning the misbehavior of sulfonyl azides in cycloaddition to alkynes prompted a study that eventually identiﬁes the optimal condition of the reaction.29 The photoinitiated cyclization involving an allene and an azido group is improved by CuI, in terms of regioselectivity in the cyclization.30 Imidocopper species are thought to undergo electrocyclization prior to demetallation.

TBSO TBSO C N3

CuI, h

H

MeCN

N H

major

(10 : 1) minor

N

Cycloaddition of N,N0 -di-t-butyldiaziridinone with conjugated dienes occurs to form 4-alkenyl-2-oxazolidinones. The less substituted double bond of the diene participates in the reaction.31 Addition reactions. (Z)-1,2-Diphosphinoalkenes are formed by a CuI-catalyzed addition of Ph2PH to 1-phosphinoalkynes.32 Functionalization of the triple bond of a 1-alkyne by TsN3 (CuI, Et3N, H2O) leads to an N-tosylcarboxamide.33 Addition of allyltributylstannane to aldehydes is also catalyzed by CuI in DMF at room temperature.34 1

Nakatani, Y., Koizumi, Y., Yamasaki, R., Saito, S. OL 10, 2067 (2008). Singh, S.K., Reddy, M.S., Mangle, M., Ganesh, K.R. T 63, 126 (2007). 3 Altman, R.A., Shaﬁr, A., Choi, A., Lichtor, P.A., Buchwald, S.L. JOC 73, 284 (2008). 4 Zhang, H., Ma, D., Cao, W. SL 243 (2007). 5 Sperotto, E., de Vries, J.G., van Klink, G.P.M., van Koten, G. TL 48, 7366 (2007). 6 Chang, J.W.W., Chee, S., Mak, S., Buranaprasertsuk, P., Chavasiri, W., Chan, P.W.H. TL 49, 2018 (2008). 7 Bao, W., Liu, Y., Lv, X. S 1911 (2008). 8 Wong, K.-T., Ku, S.-Y., Yen, F.-W. TL 48, 5051 (2007). 9 Schareina, T., Zapf, A., Ma¨gerlein, W., Mu¨ller, N., Beller, M. SL 555 (2007). 10 Li, H., Li, C. OL 8, 5365 (2006). 11 Fang, Y., Li, C. JACS 129, 8092 (2007). 12 Chen, Y.-J., Chen, H.-H. OL 8, 5609 (2006). 13 Schareina, T., Zapf, A., Ma¨gerlein, W., Mu¨ller, N., Beller, M. CEJ 13, 6249 (2007). 2

Copper(II) oxide

187

14

Ma, H.C., Jiang, X.Z. SL 1335 (2008). Jones, K.L., Porzelle, A., Hall, A., Woodrow, M.D., Tomkinson, N.C.O. OL 10, 797 (2008). 16 Xi, Z., Liu, F., Zhou, Y., Chen, W. T 64, 4254 (2008). 17 Shaﬁr, A., Lichtor, P.A., Buchwald, S.L. JACS 129, 3490 (2007). 18 Tao, C.-Z., Li, J., Fu, Y., Liu, L., Guo, Q.-X. TL 49, 70 (2008). 19 Martin, R., Larsen, C.H., Cuenca, A., Buchwald, S.L. OL 9, 3379 (2007). 20 Rivero, M.R., Buchwald, S.L. OL 9, 973 (2007). 21 Yip, S.F., Cheung, H.Y., Zhou, Z., Kwong, F.Y. OL 9, 3469 (2007). 22 Do, H.-Q., Daugulis, O. JACS 129, 12404 (2007). 23 Do, H.-Q., Daugulis, O. JACS 130, 1128 (2008). 24 Kim, J.Y., Kim, S.H., Chang, S. TL 49, 1745 (2008). 25 Cui, S.-L., Wang, J., Wang, Y.-G. OL 10, 1267 (2008). 26 Ohta, Y., Oishi, S., Fujii, N., Ohno, H. CC 835 (2008). 27 Yoo, E.J., Chang, S. OL 10, 1163 (2008). 28 Fukudome, Y., Naito, H., Hata, T., Urabe, H. JACS 130, 1820 (2008). 29 Yoo, E.J., Ahlquist, M., Kim, S.H., Bae, I., Fokim, V.V., Sharpless, K.B., Chang, S. ACIE 46, 1730 (2007). 30 Feldman, K.S., Hester II, D.K., Lopez, C.S., Faza, O.N. OL 10, 1665 (2008). 31 Yuan, W., Du, H., Zhao, B., Shi, Y. OL 9, 2589 (2007). 32 Kondoh, A., Yorimitsu, H., Oshima, K. JACS 129, 4099 (2007). 33 Cho, S.H., Chang, S. ACIE 46, 1897 (2007). 34 Kalita, H.R., Borah, A.J., Phukan, P. TL 48, 5047 (2007). 15

Copper(II) nitrate. Oxidative cleavage. Recovery of carbonyl compounds from 2-substituted 1,3dithianes is achieved by mixing with Cu(NO3)2 . 2.5H2O/montmorillonite-K10 in the air and irradiation with ultrasound.1 1

Oksdath-Mansilla, G., Penenory, A.B. TL 48, 6150 (2007).

Copper(I) oxide. Decarboxylation. Heating with Cu2O and 1,10-phenanthroline in quinoline and NMP causes decarboxylation of electron-deﬁcient aroic acids.1 1

Goossen, L.J., Rodriguez, N., Melzer, B., Linder, C., Deng, G., Levy, L.M. JACS 129, 4824 (2007).

Copper(II) oxide. N-Arylation. Amines are arylated with the aid of CuO nanoparticles under basic conditions (KOH, DMSO, air, 80– 1108).1 Another protocol indicates the use of Fe(acac)2 as cocatalyst, as demonstrated by an effective in N-arylation of pyrazole.2 1

Rout, L., Jammi, S., Punniyamurthy, T. OL 9, 3397 (2007). Taillefer, M., Xia, N., Ouali, A. ACIE 46, 934 (2007).

2

188

Copper(I) 2-thienylcarboxylate, CuTC

Copper(I) 2-thienylcarboxylate, CuTC. Coupling reactions. Conversion of oxime ethers to N-substituted imines involving NZO to NZC bond exchange is empowered by CuTC. Organostannanes and organoboronic acids can supply the substituent.1

Diels–Alder reaction. Molecules containing a conjugate diene and a terminal alkyne units that are separated by several bonds undergo intramolecular Diels–Alder reaction, as a result of transient activation of the dienophile as an alkynylcopper species.2

cupration CuOOC

Z

S

Z

1

Liu, S., Yu, Y., Liebeskind, L.S. OL 9, 1947 (2007). Fu¨rstner, A., Stimson, C.C. ACIE 46, 8845 (2007).

2

Copper(I) triﬂate. Diazoketone decomposition. Cyclopropanation of a proximal electron-rich double bond, for example, of an indole nucleus, is inescapable once carbenoid generation is initiated. By placing a moderately nucleophilic chain that is sterically interactable with the emerging cyclopropane, skeletal reorganization is feasible. Such transformation based on careful design is conducive to synthetic purposes.1

NHTs O COOMe N

N2

MeOOC

OH

N

NTs

CuOTf CH2Cl2

81%

Addition and cycloaddition. Two slightly different protocols are available for achieving addition of 1-alkynes to triﬂuoromethyl ketones:2 use either CuOTf and t-BuOK with Xantphos in THF at 608, or Cu(OTf)2 and two equivalents of t-BuOK and 1,10-phenanthroline in toluene at 1008. Cyanoformate esters can contribute the CN group as an addend to react with organoazides in a [3þ2]cycloaddition catalyzed by CuOTf.3

Copper(II) triﬂate

189

O EtO

O

CN

EtO

+ N3

CuOTf

N

CH2Cl2

MeO

N N N

MeO

1

Shen, L., Zhang, M., Wu, Y., Qin, Y. ACIE 47, 3618 (2008). Motoki, R., Kanai, M., Shibasaki, M., OL 9, 2997 (2007). 3 Bosch, L., Vilarrasa, J. ACIE 46, 3926 (2007). 2

Copper(II) triﬂate. Isomerization. N-Tosylazetidines undergo ring opening to afford the isomeric allylic amine derivatives.1 Ts N Ar

NHTs Cu(OTf)2

R

Ar

THF

R

Substitution reactions. Benzylic and allylic acetates are replaced on reaction with sulfonamides, no matter by what mechanism it proceeds, with the presence of Cu(OTf)2 and t-BuOOAc.2 Silylene insertion into allylic ethers3 is of interest to synthesis because it changes an electrophilic unit into a nucleophilic unit. OBn BnO

Si +

Si [CuOTf]2 · PhMe

Fluorination in tandem of Nazarov cyclization succeeds in the case of alkenoylarenes.4 That both reactions are catalyzed by Cu(OTf)2 is most pleasing. O

O COOR R'

F

FN(SO2Ph)2 Cu(OTf)2 ClCH2CH2Cl

COOR R'

190

Copper(II) triﬂate

Together with t-BuOOAc the sulfamidation at a benzylic or allylic position in moderate yields by PhSO2NHR is mediated by Cu(OTf)2 – 1,10-phenanthroline.5 Adamantane is also functionalized at C-1 by this method. Addition and cycloaddition reactions. Henry reaction carried out in the presence of Cu(OTf)2 and 1 is a demonstration of the possibility in developing reaction that is electronically and sterically tunable.6

Ph

Ph N

N

N N

N

(1) With catalysis of Cu(OTf)2 reactivity of imines toward attack by RZnBr is shown to be enhanced by attaching a 2-pyridinesulfonyl group to the nitrogen atom, as in 2.7

RZnBr

+ Ar

O O S N N

O O S HN N Ar R

Cu(OTf)2 CH2Cl2

(2) In cyclization of b-dicarbonyl compounds containing an alkyne which is extended outward to give cycloalkenones, there is reinforced activation by Cu(OTf)2 and an Ag salt individually, at the active methylene group and the triple bond.8

R

O

O

O R'

R R"

Cu(OTf)2 · PhH Ag salt ClCH2CH2Cl

R R

O

R R'

O

O R'

R Ar

R' = OR', R" = H

R" = Ar

N-Tosyl carbamates form carbenoids on treatment with (py)4Cu(OTf)2. The reactive species are trapped by alkenes. g,d-Unsaturated O-tosylhydroxamic acids furnish aziridino2-oxazolidinones.9

(1,5-Cyclooctadiene)bismethallylruthenium

O R

O

NHOTs

K2CO3 Me2CO

O

H

Cu(OTf)2 · (Py)4

191

N

R

O H

Carbenoids generated from a-diazoketones react with thiourea to give 2-aminothiazoles.10 Cyclodehydration follows initial trapping of the carbenoid via S-C bond formation. NH2

+ O

Cl

H2N

S

N2

F3C

NH2 Cu(OTf)2

N

Cl

S

ClCH2CH2Cl 80o

F3C

1

Ghorai, M.K., Kumar, A., Das, K. OL 9, 5441 (2007). Powell, D.A., Pelletier, G. TL 49, 2495 (2008). 3 Bourque, L.E., Cleary, P.A., Woerpel, K.A. JACS 129, 12602 (2007). 4 Nie, J., Zhu, H.-W., Cui, H.-F., Hua, M.-Q., Ma, J.-A. OL 9, 3053 (2007). 5 Pelletier, G., Powell, D.A. OL 8, 6031 (2006). 6 Ma, K., You, J. CEJ 13, 1863 (2007). 7 Esquivias, J., Arrayas, R.G., Carretero, J.C. ACIE 46, 9257 (2007). 8 Deng, C.-L., Guo, S.-M., Xie, Y.-X., Li, J.-H. EJOC 1457 (2007). 9 Lebel, H., Lectard, S., Parmentier, M. OL 9, 4797 (2007). 10 Yadav, J.S., Reddy, B.V.S., Rao, Y.G., Narsaiah, A.V. TL 49, 23815 (2008). 2

Copper(II) triﬂuoroacetate. Cycloaddition. Oxaziridines are made to condense with alkenes (e.g., the more electron-rich double bond of a diene) via ring opening to give oxazolidines.1 Ph Ph N O

SO2Ph +

COOEt

HMPA CH2Cl2

SO2Ph N

Cu(OCOCF3)2

O COOEt

1

Michaelis, D.J., Ischay, M.A., Yoon, T.P. JACS 130, 6610 (2008).

(1,5-Cyclooctadiene)bismethallylruthenium. Hydroamination. Amides, lactams, carbamates and ureas add to 1-alkynes to give enamide derivatives. The stereoselectivity of this anti-Markovnikov addition is sensitive to phosphine ligands that are present.1 1

Goossen, L.J., Rauhaus, J.E., Deng, G. ACIE 44, 4042 (2005).

192

(1,5-Cyclooctadiene)platinum(II) triﬂate

(1,5-Cyclooctadiene)platinum(II) triﬂate. Hydroamination. Sulfonamides and weakly basic anilines add to alkenes with yields .95%, when catalyzed by (cod)Pt(OTf)2.1 Interestingly, (cod)RhBF4 [also with DPPB ligand] induces intramolecular hydroamination in the anti-Markovnikov fashion.2

NHMe Ph

R

Me N

[(cod)Rh(dppb)]BF4 THF 70°

Ph

R

1

Karshtedt, D., Bell, A.T., Tilley, T.D. JACS 127, 12640 (2005). Takemiya, A., Hartwig, J.F. JACS 128, 6042 (2006).

2

(1,3,5-Cyclooctatriene)bis(dimethyl fumarate)ruthenium. Cross-coupling.1 Chain extension of N-vinylcarboxamides at the terminal sp 2-carbon atom with alkyl or alkenyl residue on reaction with alkenes or alkynes is catalyzed by the Ru complex. 1

Tsujita, H., Urz, Y., Matsuki, S., Wada, K., Mitsudo, T., Kondo, T. ACIE 46, 5160 (2007).

Cyclopentadienyl(h6-naphthalene)ruthenium hexaﬂuorophosphate. Hydration.1 Anti-Markovnikov hydration of 1-alkynes to afford aldedydes is accomplished by treatment with the title complex and a 2-diphenylphosphino-6-arylpyridine. 1

Labonne, A., Kribber, T., Hintermann, L. OL 8, 5853 (2006).

( p-Cymene)(N-tosyl-1,2-diphenylethylenediamine)ruthenium. Reduction.1 In the presence of the Ru complex, b-diketones are chemoselectively and enantioselectively reduced by HCOONHEt3. An aliphatic ketone group is reduced in preference to an aryl ketone. 1

Matsukawa, Y., Isobe, M., Kotsuki, H., Ichikawa, Y. JOC 70, 5339 (2005).

D Dess-Martin periodinane. Oxidation.1 The title reagent is useful for oxidation of b-hydroxy-a-diazo esters at room temperature to furnish a-diazo b-keto esters. 1

Li, P., Majireck, M.M., Korboukh, I., Weinreb, S.M. TL 49, 3162 (2008).

1,4-Diazabicyclo[2.2.2]octane, DABCO. Rearrangement.1 Allyl acrylates are converted into a-allylated acrylic acids on treatment with DABCO and Me3SiCl. Rearrangement is induced by conjugate addition to generate ester enolates. 1

Li, Y., Wang, Q., Goeke, A., Frater, G. SL 288 (2007).

1,8-Diazabicyclo[5.4.0]undec-7-ene, DBU. Desilylation. Removal of the silyl group from a silylalkyne is effected by heating with DBU at 608 in H2O –MeCN (1 : 19).1 Michael reaction. An intramolecular Michael reaction with concomitant elimination is synthetically most pleasing. The following example serves to elaborate a complex bridged ring system under mild conditions.2 O O OMs O

COOEt

O

O

DBU

O

THF

COOEt 96%

Because of steric effects epimerization can intervene in an intramolecular addition catalyzed by DBU.3

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 193

194

Di-t-butyl dicarbonate

H

H

O

H

Ph

O

DBU

O

O

HO

CH2Cl2

H

H

epimerized

Ph

O

DBU

O HO

O

O

Ph

O

O H

O

H

O

O H

H

H

O

Ph

O

O

CH2Cl2

H

O

O H

DBU also promotes conjugate addition of amines to a,b-unsaturated esters, nitriles, and ketones.4 Aldol reaction. As a suitable base for catalyzing an intramolecular aldol reaction between an a-benzoyloxy ketone and an aldehyde, DBU also promotes transesteriﬁcation of the product.5 H

H O

OBz

O

O OR H H

O

CHO

O O OR

DBU

H

PhH

H

OH OBz

1

Yeom, C.-E., Kim, M.J., Choi, W., Kim, B.M. SL 565 (2008). Prabhudas, B., Clive, D.L.J. ACIE 46, 9295 (2007). 3 Lee, H., Kim, K.W., Park, J., Kim, H., Kim, S., Kim, D., Hu, X., Yang, W., Hong, J. ACIE 47, 4200 (2008). 4 Yeom, C.-E., Kim, M.-J., Kim, B.-M. T 63, 904 (2007). 5 Watanabe, H., Nakada, M. JACS 130, 1150 (2008). 2

Di-t-butyl dicarbonate. Isothiocyanate esters.1 Boc2O serves to promote elimination of H2S from adducts of RNH2 and CS2. A catalytic amount of DMAP or DABCO is also added to the reaction. Carbamates.2 Acylation of amines by Boc2O is catalyzed by thiourea. 1

Munch, H., Hansen, J.S., Pittelkow, M., Christensen, J.B., Boas, U. TL 49, 3117 (2008). Khaksar, S., Heydari, A., Tajbakhsh, M., Vahdat, S.M. TL 49, 3527 (2008).

2

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, DDQ

195

Dibutyliodotin hydride. Additive cleavage.1 Dibutyliodostannyl radical generated from Bu2Sn(I)H cleaves methylenecyclopropanes regioselectively. Addition of the resulting C-radical to a proximal double bond leads to a cyclic product. The alkenylstannane unit is amenable to Stille coupling. Bu Ph

Bu

I Sn Ph

Bu2Sn(H)I

O

O

1

Hayashi, N., Hirokawa, Y., Shibata, I., Yasuda, M., Baba, A. JACS 130, 2912 (2008).

Dicarbonylhydrido-h5-[1,3-bis(trimethylsilyl)-2-hydroxy-4,5,6,7tetrahydroindenyl]iron. Hydrogenation.1 The iron complex 1 is a highly selective hydrogenation catalyst for reducing the carbonyl group. Double bond, triple bond, halogen atoms, cyclopropane and pyridine rings are not affected. O

SiMe3 OH SiMe3 OC Fe OC

H2

(1) / Et2O

H OH

(1) 87% 1

Casey, C.P., Guan, H. JACS 129, 5816 (2007).

Dichloramine T. Deoximation.1 To the numerous procedures for recovery of carbonyl compounds from oximes is added one involving oxidation with TsNCl2 in aqueous MeCN. 1

Gupta, P.K., Manral, L., Ganesan, K. S 1930 (2007).

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, DDQ. Oxidative cyclization. An expedient method for synthesis of cis-2,6-disubstituted 4-pyranones involves intramolecular trapping of oxallyl cation which is generated by DDQ oxidation.1

196

Dichloro(diethene)rhodium

OAc

O OAc

O

DDQ

OAc

H

OAc

H

OAc

O

H

80%

Ether cleavage. An allylic p-methoxybenzyl ether is selectively cleaved with DDQ in a buffer solution, thereby facilitating the progress in a synthesis of multipolide-A.2

O

O O

PMBO

O

HO DDQ

O

PMBO

CH2Cl2 buffer

O

O

PMBO O

1

Tu, W., Liu, L., Floreancig, P.E. ACIE 47, 4184 (2008). Ramana, C.V., Khaladkar, T.P., Chatterjee, S., Gurjar, M.K. JOC 73, 3817 (2008).

2

Dichloro(diethene)rhodium. Cycloaddition. Unsaturated carbodiimides and alkynes are combined to afford bicyclic amidines, under the inﬂuence of (C2H4)2RhCl2 and an aminodialkoxyphosphine ligand1.

+

NAr C N

NAr Rh(C2H4)2Cl2 Ar O

R

O Ar

Ar O P N O Ar

N R

H

(Ar = m-xyl) 1

Yu, R.T., Rovis, T. JACS 130, 3262 (2008).

Dichlorobis( p-cymene)(triphenylphosphine)ruthenium(II). Addition to 1-alkenes. Addition of polyhaloalkanes (e.g., CCl4) to 1-alkenes by catalysis of Ru complexes (instead of free radical initiators) is enhanced by microwave irradiation.1 R + CCl4 1

Cl

(p-cymene)Ru(PPh3)3Cl2 w

R

CCl3

Borguet, Y., Richel, A., Delfosse, S., Leclerc, A., Delaude, L., Demonceau, A. TL 48, 6334 (2007).

Di(ethene)trispyrazolylboratoruthenium

197

Dichloro(norbornadiene)bis(triphenylphosphine)ruthenium(II). Cycloaddition. The title complex is employed to catalyze intramolecular homoDiels–Alder reaction.1

(nbd)Ru(PPh3)2Cl2

R

dioxane

Z

Z R Z = O, NTs, CX 2 1

Tenaglia, A., Gaillard, S. OL 9, 3607 (2007).

Dichloro(pyridine-2-carboxylato)gold(III). Cyclization. The Au(III) complex induces cyclization of silyl ethers of alkenyl/ a-oxallenyl carbinols to form easily fragmentable bicyclo[3.1.0]hexan-6-ol intermediates, which give rise to 3-acylcyclopentenes.1 Since the substrates are prepared from conjugated carbonyl compounds the 3-step process represents a unique annulation method. Me3SiO

OMOM

OHC

OMOM C

H O

MOMO Me3SiO

C

N O Au Cl Cl

MOMO O

H 1

Huang, X., Zhang, L. JACS 129, 6398 (2007).

Dichlorotris(triphenylphosphine)ruthenium(II). Acetals. Isomerization of allylic ethers to enol ethers by the Ru complex enables addition of alcohols to form acetals.1 1

Krompiec, S., Penczek, R., Kuznik, N., Malecki, J.G., Matlengiewicz, M. TL 48, 137 (2007).

Di(ethene)trispyrazolylboratoruthenium. Hydroamination. Addition of amines to 1-alkynes afford enamines (from secondary amines) or imines (from primary amines), when the components are heated with TpRu(C2H4)2 and Ph3P in toluene at 1008.1 1

Fukumoto, Y., Asai, H., Shimizu, M., Chatani, N. JACS 129, 13792 (2007).

198

Dicobalt octacarbonyl

Dicobalt octacarbonyl. Pauson –Khand reaction. In the presence of tetramethylthiourea the Pauson–Khand reaction suceeds with enynes in which the double bond is present in a silylcyclopropene unit. It enables a synthesis of the angular triquinane sesquiterpene (-)-pentalenene.1 COOEt

EtOOC SiMe3 Co2(CO)8

SiMe3

O

(Me2N)2CS

SiMe2Ph

SiMe2Ph

The CvN bond of a carbodiimide is shown to participate in a Pauson –Khand reaction, forming g-imino-a,b-unsaturated-g lactams.2

R' NR N

C

R' O

CO Co2(CO)8

NR

(Me2N)2CS PhMe 70o

N

Cyclocarbonylation. An intriguing transformation of certain epoxy enynes entails double carbonylation and cyclization.3

H

O

H

O

O

H

Co2(CO)8 PhH

r

R

H

H

O R = Ph 82%

Homologation. Epoxides undergo ring opening and chain elongation to afford b-hudroxy esters when they are exposed to Co2(CO)8 under CO (1 atm.) in MeOH.4 1

Pallerla, M.K., Fox, J.M. OL 9, 5625 (2007). Aburano, D., Yoshida, T., Miyakoshi, N., Mukai, C. JOC 72, 6878 (2007). 3 Odedra, A., Lush, S.-F., Liu, R.-S. JOC 72, 567 (2007). 4 Denmark, S.E., Ahmad, M. JOC 72, 9630 (2007). 2

Dicyclohexylboron chloride. Hydroxyalkylation.1 Primary amides and aldehydes combine in the presence of Cy2BCl and Et3N in ether. 1

Kiran, S., Ning, S., Williams, L.J. TL 48, 7456 (2007).

Diisobutylaluminum hydride, Dibal-H

199

Diﬂuoro(4-triﬂuoromethylphenyl)bromane. Oxidative condensation.1 The title reagent converts a mixture of alkynes and primary alcohols to afford enones, in the presence of BF3 . OEt2. O R

+ HO

R"

R'

F2Br

CF3

R

R" R'

BF3 · OEt2

Aziridination.2 Ylides of the structure [CF3SO2NBrC6H4CF3] are formed by mixing the l3-bromane with CF3SO2NH2 in MeCN that can cycloadd to alkenes to give N-triﬂylaziridines. 1

Ochiai, M., Yoshimura, A., Mori, T., Nishi, Y., Hirobe, M. JACS 130, 3742 (2008). Ochiai, M., Kaneaki, T., Tada, N., Miyamoto, K., Chuman, H., Shiro, M., Hayashi, S., Nakanishi, W. JACS 129, 12938 (2007).

2

Diiodine pentoxide. Oxidation.1 Benzylic alcohols are oxidized by I2O5 with KBr as activator in H2O at room temperature. 1

Liu, Z.-Q., Zhao, Y., Luo, H., Chai, L., Sheng, Q. TL 48, 3017 (2007).

1,3-Diiodo-5,5-dimethylhydantoin. Nitriles. Primary alcohols and amines are converted to nitriles on treatment with aqueous ammonia and the title reagent.1 1

Iida, S., Togo, H. SL 407 (2007).

Diisobutylaluminum hydride, Dibal-H. Reduction. At –788, selective reduction of 1-alkylindole-2,3-dicarboxylic esters at the C-2 substituent (to a CHO group) by Dibal-H is observed.1 Generally, the ester to aldehyde conversion can be performed at 08 with alkali metal diisobutyl(t-butoxy)aluminum hydride, which is formed by adding t-BuOM (M ¼ Na, Li) to Dibal-H in THF.2,3 Rearrangement.4 A cyclopropyl group is liable to expand during reduction of a neighboring amidic carbonyl.

O RN

O NR'

i-Bu2AlH BF3 · OEt2

O

Et3SiH

RN

NR'

200

N, N-Diisopropylaminoborane

Hydroalkylation.5 2-Alkynoic esters form ketene Al-enolates on treatment with Dibal-H and NMO. The enolate species react with epoxides regioselectively. Further processing leads a-alkylidene-g-butyrolactones in either the (E)-form or (Z)-form. Ar R

R i-Bu2AlH

COOEt

O

C

NMO THF

EtO

O

R

BF3

Al

OH

EtOOC

Ar

1

Sayyed, I.A., Alex, K., Tillack, A., Schwarz, N., Spannenberg, A., Michalik, J., Beller, M. T 64, 4590 (2008). 2 Song, J.I., An, D.K. CL 36, 8863 (2007). 3 Kim, M.S., Choi, Y.M., An, D.K. TL 48, 5061 (2007). 4 Methot, J.L., Dunstan, T.A., Mampreian, D.M., Adams, B., Altman, M.D. TL 49, 1155 (2008). 5 Ramachandran, P.V., Garner, G., Pratihar, D. OL 9, 4753 (2007).

N,N-Diisopropylaminoborane. Reduction and coupling.1 The title reagent is generated from lithium N,N-diisopropylaminoborohydride on treatment with Me3SiCl at room temperature. It reduces esters and nitriles in the presence of LiBH4 (catalyst). It serves as a source of boron in the preparation of arylboronic acids from ArBr by a Pd-catalyzed coupling reaction. 1

Pasumansky, L., Haddenham, D., Clary, J.W., Fisher, G.B., Goralski, C.T., Singaram, B. JOC 73, 1898 (2008).

Dilauroyl peroxide. Radical cyclization. Amido radicals are generated from N0 -methyldithiocarbonylhydrazides by heating with dilauroyl peroxide. Setting up the functional group in juxtaposition to a double bond invites intramolecular addition that even further implications in ring formation are envisaged. As a key step in a synthesis of the amaryllidaceae alkaloid fortucine the value of such a process is demonstrated.1

O SMe MeO

O

S NPh N

MeO O

O

O dilauroyl peroxide

MeO

Cl

MeO

OTBS Cl

H H O

60%

N

OTBS

4-Dimethylaminopyridine, DMAP

201

Addition reactions. 3-Aryl- and 3-formylpyrroles are alkylated by heating with the xanthates (XCH2SCvS)OEt and dilauroyl peroxide. The activated carbon chain CH2X (X ¼ CN, COOEt, Ac, . . .) is introduced to C-2.2 1

Biechy, A., Hachisu, S., Quiclet-Sire, B., Ricard, L., Zard, S.Z. ACIE 47, 1436 (2008). Guadarrama-Morales, O., Mendez, F., Miranda, L.D. TL 48, 4515 (2007).

2

Dimanganese decacarbonyl. Alkyl radicals. Iodine atom abstraction from alkyl iodides occurs on irradiation with Mn2(CO)10. The carbon radicals thus generated are readily trapped by hydrazones.1,2 OBn

OBn

BnO

BnO OH I

Ph

+ N N

TBSO

O

OH Mn2(CO)10

H

Ph

H N

InCl3 hv / CH2Cl2

N TBSO

O

O

O 93%

1

Korapala, C.S., Qin, J., Fristad, G.K. OL 9, 4243 (2007). Fristad, G.K., Ji, A. OL 10, 2311 (2008).

2

4-Dimethylaminopyridine, DMAP. Esteriﬁcation. A useful protocol for esteriﬁcation of alcohols by anhydrides under solvent-free conditions involves only catalytic amounts of DMAP, without any auxiliary base.1 6-O-Protected octyl b-D-glucopyranosides are selectively (.99%) acylated by treatment with an acid anhydride and DMAP in toluene maintaining at – 208 to 2408.2 Hydroxyl groups at C-2 and C-4 are untouched. Rearrangement.3 Furo[2,3-c](3aH,5H )quinoline-2,4-diones are converted into the isomeric furo[3,4-c](1H,5H )quinoline-3,4-diones, on heating with DMAP. Apparently, isocyanate intermediates are formed via opening of the six-membered heterocycle. O R

O

O

O

DMAP

N H 1

R O

N H

O

Sakakura, A., Kuwajiri, K., Ohkubo, T., Kosugi, Y., Ishihara, K. JACS 129, 14775 (2007). Muramatsu, W., Kawabata, T. TL 48, 5031 (2007). 3 Kafka, S., Kosmrlj, J., Klasek, A., Pevec, A. TL 49, 90 (2008). 2

202

Dimethyldioxirane

Dimethyldioxirane. Epoxidation.1 The reaction of N-allenylamides with dimethyldioxirane results in a-(1-oxyvinyl)iminium species, which can be trapped by pyrroles in a [4þ3]cycloaddition.

O

O

O

O

O

O

O O

N

N

N O

C

O RN

O

N

H

O O

NR H

1

Antoline, J.E., Hsung, R.P., Huang, J., Song, Z., Li, G. OL 9, 1275 (2007).

Dimethylsulﬁde – halogen. a-Halo-a,b-unsaturated esters.1 Oxidation of primary alcohols by the reagent complex in the presence of Et3N and a triphenylphosphoranylacetic ester enables a Wittig reaction which is also followed by halogenation and dehydrohalogenation. 1

Jiang, B., Dou, Y., Xu, X., Xu, M. OL 10, 593 (2008).

Dimethylsulfoxonium methylide. Methylenation.1 While cyclic ketones undergo Corey–Chaykovsky reaction to deliver epoxides at room temperature, excess amounts of base suppress the transformation and at high temperature the ketones are converted into 1,2-dimethylenecycloalkanes.

Me2S=CH2

O

diglyme 130o

95% Me2S=CH2 25o

O

Diphenyliodonium triﬂuoroacetate

203

Methylene insertion.2 o-Hydroxydiaryl ketones give 3-arylbenzofurans, which are apparently derived from a normal Corey –Chaykovsky reaction. Additionally, insertion of a CH2 group between the carbonyl and one of the aryl residues also occurs. O

Ar

O

Ar

X

O

Me2S=CH2

X

DMSO

OH

X O

O

OH O Ar

Ar O2N

Ar

OH

O2 N

OH

1

Butova, E.D., Fokin, A.A., Schreiner, P.R. JOC 72, 5689 (2007). Chitimalla, S.K., Chang, T.-C., Liu, T.-C., Hsieh, H.-P., Liao, C.-C. T 64, 2586 (2008).

2

1,1-Dioxonaphtho[1,2-b]thiophene-2-methoxycarbonyl chloride. Amino group protection. Title reagent 1 is proposed to derivatize amines for their protection. Mild conditions are needed to cleave the derived carbamates.1

O S O O O

Cl

(1) 1

Carpino, L.A., Abdel-Maksoud, A.A., Ionescu, D., Mansour, E.M.E., Zewail, M.A. JOC 72, 1729 (2007).

Diphenyldiazomethane. Benzhydryl ethers. The title reagent protects alcohols on heating in an inert solvent.1 1

Best, D., Jenkinson, S.F., Rule, S.D., Higham, R., Mercer, T.B., Newell, R.J., Weymouth-Wilson, A.C., Fleet, G.W.J., Petursson, S. TL 49, 2196 (2008).

Diphenyliodonium triﬂuoroacetate. Phenylation. The reagent reacts with arylamines in reﬂuxing DMF to give ArNHPh.1 1

Carroll, M.A., Wood, R.A. T 63, 11349 (2007).

204

S,S-Diphenyl-N-(o-nitrobenzenesulfenyl)-N0 -tosylsulfodiimide

S,S-Diphenyl-N-(o-nitrobenzenesulfenyl)-N0 -tosylsulfodiimide. Aziridination. Mild thermolysis of the title reagent TsNvS(Ph2)vNSAr in MeCN liberates the nitrene [ArS-N], which is intercepted by alkenes. 1

Yoshimura, T., Fujie, T., Fujii, T. TL 48, 427 (2007).

Diphenylphosphonyl azide. Carbamoyl azides. Azidocarbonylation of amines to form RNHCON3 starts from formation of carbamate salts in the reaction with CO2 (catalyzed by tetramethyl-2-phenylguanidine) which is followed by treatment with Ph2P(O)N3.1 1

Garcia-Egido, E., Fernandez-Suarez, M., Munoz, L. JOC 73, 2909 (2008).

Dipyridyliodonium tetraﬂuoroborate. Glycosyl ﬂuorides.1 O-Protected thioglycosides are converted to glycosyl ﬂuorides at room temperature by the title reagent, for example, Glu(b)SPh to Glu(a)F. If the reaction medium also contains TfOH and ROH, glycosides are obtained. 1

Huang, K.-T., Winssinger, N. EJOC 1887 (2007).

N,N0 -Ditosylhydrazine. Diazoacetic esters.1 Diazoacetic esters are prepared from reaction of bromoacetic esters and TsNHNHTs and DBU (base) in THF at 08. 1

Toma, T., Shimokawa, J., Fukuyama, T. OL 9, 3195 (2007).

E Erbium(III) triﬂate. b-Amino alcohols. Epoxides are opened by amines in water at 608, Er(OTf)3 shows catalytic activity for this transformation.1 1

Procopio, A., Gaspari, M., Nardi, M., Oliverio, M., Rosati, O. TL 49, 2269 (2008).

Ethyl(carboxysulfamoyl)triethylammonium hydroxide, Burgess reagent. Oxidative dimerization. Conversion of thiols to disulﬁdes by the Burgess reagent is reported, despite the economic irrationality involved.1 Sulﬁlimine formation. Reaction of sulfoxides with the Burgess reagent at room temperature delivers sulﬁlimines.2 1

Banﬁeld, S.C., Omori, A.T., Leisch, H., Hudlicky, T. JOC 72, 4989 (2007). Raghavan, S., Mustafa, S., Rathore, K. TL 49, 4256 (2008).

2

Ethyl tribromoacetate. Acyl bromides. Heating aldehydes with Br3COOEt and (PhCOO)2 in toluene accomplishes radical bromination.1 1

Kang, D.H., Joo, T.Y., Chavasiri, W., Jang, D.O. TL 48, 285 (2007).

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 205

F Fluoroboric acid. Michael reaction. Efﬁcient addition of thiols to conjugated carbonyl compounds proceeds in the presence of a catalyst derived from HBF4 adsorbed in silica gel.1 1

Sharma, G., Kumar, R., Chakraborti, A.K. TL 49, 4272 (2008).

Fluorosulfuric acid – antimony(V) ﬂuoride. Cyclization. Intramolecular Friedel –Crafts alkenylation of v-aryl-1,1-diﬂuoroalkenes can be applied to a synthesis of tetrahydro[6]helicenes.1

F

F

FSO3H SbF5 (CF3)2CHOH 0o

62% 1

Ichikawa, J., Yokota, M., Kudo, T., Umezaki, S. ACIE 47, 4870 (2008).

Fluorous reagents and ligands. Amide formation. Development of a carbodiimide reagent (1) containing at one end an isopropyl group and at the other end a chain ending in two polyﬂuorinated branches has been reported.1 C6F13 N C N

C6F13 O

(1) Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 207

208

Formaldehyde

Sonogashira coupling. The method for Sonogashira coupling that employs Pd(OSO2C8F17)2/3-PyCH(OC8F17)2 in a mixture of toluene and perﬂuorodecalin truly demonstrates the synthetic utility of ﬂuorous compounds.2 Mitsunobu reagent. Pairing bis[3-(nonatriﬂuoro-t-butoxypropyl)] azodicarboxylate with Ph3P constitutes a ﬂuorous version of the Mitsunobu reagent.3 Diels–Alder reaction. Rate enhancement of the Diels –Alder reaction is noted in aqueous perﬂuorinated emulsions (from perﬂuorohexane and lithium perﬂuorooctanesulfonate).4 Separation technique. o-Nitrobenzenesulfonamides that are left behind from incomplete alkylation are rapidly and quantitatively separated by treatment with a highly reactive C8F17CH2CH2CH2I followed by ﬂuorous solid-phase extraction.5 1

del Pozo, C., Keller, A.I., Nagashima, T., Curran, D.P. OL 9, 4167 (2007). Yi, W.-B., Cai, C., Wang, X. EJOC 3445 (2007). 3 Chu, Q., Henry, C., Curran, D.P. OL 10, 2453 (2008). 4 Nishimoto, K., Kim, S., Kitano, Y., Tada, M., Chiba, K. OL 8, 5545 (2006). 5 Basle, E., Jean, M., Gouault, N., Renault, J., Uriac, P. TL 48, 8138 (2007). 2

Formaldehyde. 2-Methylene-3-butenal. The valuable dienophile is readily prepare from crotonaldehyde and aq. HCHO.1

CHO

HCHO (C4H4)NH

OHC

CHO C5H6

EtCOOH

CHO

1

Zou, Y., Wang, Q., Goeke, A. CEJ 14, 5335 (2008).

Formic acid. Double bond cleavge.1 A surprising oxidative cleavage of 1,2,3,4-tetraaryl-2-butene1,4-diones to afford benzils in good yields (instead of forming the furans) occurs when they are irradiated by microwaves in formic acid and a catalytic amount of conc. H2SO4. 1

Rao, H.S.P., Jothilingam, S., Vasantham, K., Scheeren, H.W. TL 48, 4495 (2007).

G Gallium(III) chloride. Diels–Alder reaction.1 Allylsilanes and propargylsilanes condense with N-arylaldimines in the presence of GaCl3 to provide 2,4-disubstituted tetrahydroquinolines and quinolines, respectively. 1

Hirashita, T., Kawai, D., Araki, S. TL 48, 5421 (2007).

Gallium(III) triﬂate. Fluoroalkyl heterocycles.1 Condensation of o-functionalized (OH, SH, NH2) anilines with ﬂuoroalkyl ketones leads to benzoxazolines, benzthiazolines, benzimidazolines, . . . bearing a ﬂuorinated carbon chain at C-2. The reaction is promoted by Ga(OTf)3. 1

Prakash, G.K.S., Mathew, T., Panja, C., Vaghoo, H., Venkataraman, K., Olah, G.A. OL 9, 4627 (2007).

Gold. O-Silyl ethers. Gold nanoparticles are found to be effective catalyst for derivatization of aldehydes by Me3SiCN to afford O-trimethylsilyl cyanohydrins at room temperature.1 Primary alcohols are converted into silyl ethers by R3SiH using nanosized gold particles supported on alumina.2 Under the same conditions aromatic aldehydes are coupled and silylated. Similarly supported gold particles prepared from HAuCl4 and NaOH on CeO2 or ZrO2 have found use in the three-component condensation of aldehydes, amines and alkynes.3

+ R'CHO NHTs

+ R2NH

R'

Au/ZrO 2 dioxane 100o

N Ts

NR2

Hydrogenation. Gold-on-titanium dioxide is a special catalyst with which nitroalkenes are converted into saturated oximes.4 Thus only the sidechain is affected when o,b-dinitrostyrene is subjected to the hydrogenation conditions in its presence. Conventional hydrogenation (Pd/C, Pt/C) of the same compound leads to indole and diamine products. Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 209

210

Gold(III) bromide

NO2

N

Au/TiO2 90–100 o

NO2

OH

NO2 96%

1

Cho, W.K., Lee, J.K., Kang, S.M., Chi, Y.S., Lee, H.-S., Choi, I.S. CEJ 13, 6351 (2007). Raffa, P., Evangelisti, C., Vitulli, G., Salvadori, P. TL 49, 3221 (2008). 3 Zhang, X., Corma, A. ACIE 47, 4358 (2008). 4 Corma, A., Serna, P., Garcia, H. JACS 129, 6358 (2007). 2

Gold(III) bromide. Glycosylation. By taking advantage of the afﬁnity of gold ions for the triple bond, 1,2-ortho esters of sugars containing a propargyloxy unit have been designated as latent glycosyl donors. Glycosylation using AuBr3 gives 2-benzoyloxy glycosides.1

OR (RO)n

OR

O

AuBr3 – R'OH CH2Cl2 4A-MS

O O Ph O

O

(RO)n

OR'

O O Ph

1

Sureshkumar, G., Hotha, S. TL 48, 6564 (2007).

Gold(I) chloride. Spiroacetals. 1,1-Addition of hydroxyl groups to a triple bond in creating spiroacetal systems has been realized in the presence of AuCl.1

OMe H O HO

O H

O

AuCl

OR

PyHOTs

O

H

O

MeOH

O

OR

H OPMB

PMBO

Isomerization. o-alkynylaroic acids undergo Au-catalyzed cyclization.2 There is a possibility of forming either the phthalide or the isocoumarin system.2

Gold(I) chloride – tertiary phosphine

R

R

R

AuCl

+

O

K2CO3 MeCN 25o

COOH

211

O

R

O O

R AuCl 3

O

H2O (2 eq)

COOR'

MeCN 50o

O

From the S-silyl derivatives of o-alkynylarylthiols, cycloisomerization leads to 3-silylbenzothiophenes.3 The gold salt is found to be highly effective in promoting Meyer– Schuster rearrangement.4 Cycloelimination. On exposure to AuCl, esters of 1,4,5-alkatrien-3-ols are subject to cycloisomerization and elimination to provide benzene derivatives.5 O

R

OBn R

+

C

+ R'COX

OCOR' OBn C

R OBn

AuCl CH2Cl2

1

Li, Y., Zhou, F., Forsyth, C.J. ACIE 46, 279 (2007). Marchal, E., Uriac, P., Legouin, B., Toupet, L., van de Weghe, P. T 63, 9979 (2007). 3 Nakamura, I., Sato, T., Terada, M., Yamamoto, Y. OL 9, 4081 (2007). 4 Lopez, S.S., Engel, D.A., Dudley, G.B. SL 949 (2007). 5 Huang, X., Zhang, L. OL 9, 4627 (2007). 2

Gold(I) chloride – tertiary phosphine. Cycloisomerization. N-Allenyl-N-arylcarbamates cyclize to afford 1,4-dihydroquinoline derivatives, when catalyzed by AuCl and 2-(di-t-butylphosphino)biphenyl.1

AuCl

C N COOMe

P Ph

dioxane

N COOMe

Sonogashira coupling. Use (Ph3P)AuCl instead of Pd catalyst, the Sonogashira coupling is effected without a copper salt.2 1

Watanabe, T., Oishi, S., Fujii, N., Ohno, H. OL 9, 4821 (2007). Gonzalez-Arellano, C., Abad, A., Corma, A., Garcia, H., Iglesias, M., Sanchez, F. ACIE 46, 1536 (2007).

2

212

Gold(I) chloride – 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene/silver salts

Gold(I) chloride – 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene/silver salts. 1,3-Rearrangement. 3-Acetoxy-1-alkenes undergo isomerization to give the 1-acetoxy isomers on heating with the Au(I) complex in 1,2-chichloroethane.1 Addition. Addition of ROH to allenes results in the generation of allylic ethers. The Au(I)-catalyzed reaction is regioselective, the products retain the most stable double bond.2

AuCl, AgOTf

C

RO

Ph N

Ph

N ..

Hydroﬂuorination of alkynylarenes delivers (Z)-b-ﬂuorostyrenes on treatment with 3HF Et3N and catalytic amounts of the Au complex.3 Quinoline synthesis. the Au(I) complex.4

2-Acylarylamines and alkynes condense under the inﬂuence of

R

R O

NH2

AuCl, AgOTf

+ R'

N

N

N

R'

..

Cycloaddition. Cyclopropanation of the double bond(s) in dienynes is observed, with the sp-hybridized carbon atom(s) behaving like carbene(s). The transformation is highly efﬁcient while giving intriguing polycyclic isomers.5

TsN

TsN

AuCl, AgSbF 6

+

TsN N

N ..

70%

30%

Oxidative transformations. Addition of Ph2SO to the reaction has the effect of converting one of the sp-hybridized carbon atoms of an enyne into a carbonyl group while modiﬁcation of the molecular skeleton takes place.6

Gold(I) chloride – tertiary phosphine/silver salts

213

CHO Z

+

AuCl, AgSbF 6

Ph2SO

R

N

Z

R H

N ..

N

N3 +

Ph

Ph2SO O

Ph

73% O

CHO

Ph

O

+

O

Ph2SO

Ph

O 73%

1

Marion, N., Gealageas, R., Nolan, S.P. OL 9, 2653 (2007). Zhang, Z., Widenhoefer, R.A. OL 10, 2079 (2008). 3 Akana, J.A., Bhattacharyya, K.X., Mu¨ller, P., Sadighi, J.P. JACS 129, 7736 (2007). 4 Liu, X.-Y., Ding, P., Huang, J.-S., Che, C.-M. OL 9, 2645 (2007). 5 Kim, S.M., Park, J.H., Choi, S.Y., Chung, Y.K. ACIE 46, 6172 (2007). 6 Witham, C.A., Mauleon, P., Shapiro, N.D., Sherry, B.D., Toste, F.D. JACS 129, 5838 (2007). 2

Gold(I) chloride – tertiary phosphine/silver salts. Vinyl ethers and esters.1 From readily available ROCHvCH2 and through an exchange reaction catalyzed by (Ph3P)AuCl –AgOAc a great variety of vinyloxy compounds are prepared. Substitution reactions. Alkyl 2-alkynylbenzoates are activated by the Au(I) salt toward formation of isocoumarin, thereby weakening the OZC(alk) bond of the esters. Attack of nucleophiles results in the cleavage of the esters.2,3 Particularly noteworthy is the formation of tetralins by way of an intramolecular reaction involving an aromatic ring (a C-nucleophile).3 R

O

O O

R O Ph

(Ph 3P)AuCl– AgOTf

+ Ph

Cyclizations. Intramolecular hydroamination to form 5- and 6-membered heterocycles4 occurs on unactivated CvC bonds by heating the ammonium salts with AuCl,

214

Gold(I) chloride – tertiary phosphine/silver salts

ArPCy2, and AgOTf in PhMe at 808. By a similar process O-propargyl hydroxylamines give isoxazolines.5 N-Boc derivatives of propargylic amines lose isobutene to furnish 5-alkylidene-2-oxazolidinones.6 Twofold addition involving heteroatom and C-nucleophiles are exempliﬁed in the formation of 2,3-benzo-9-oxabicyclo[3.3.1]nonanes7 and the tricyclic 2,20 -bipyrrolyl derivatives.8

R

R'

(Ph3P)AuCl–AgOTf

R'

OH

R

ClCH2CH2Cl

O X

X X = O, NTs, CH 2

O O N

N H

N

(Ph3P)AuCl–AgOTf PhMe

N

Molecules containing allene and propargylic alcohol subunits are activated toward cyclization. It is found that Au(I) and Pt(IV) salts promote different modes of reaction. Allene activation takes precedence with (Ph3P)AuSbF6.9 Me3Si

HO SiMe3 (Ph3P)AuCl–AgOTf

O

C

O

OTBS

HO * C

n

OTBS PtCl4

n H

1-Alkynes can be used as external nucleophiles that participate in the second stage of the reaction. Pyrrolo[1,2-a]quinolines are generated.10

Gold(I) chloride – tertiary phosphine/silver salts

P

AuCl

Ar'

R Ph

R

+

R

AgOTf

Ar'

NHAr

215

N

R

X

The synthesis of 2-alkoxypyridines from 1-alkoxy-3-alken-1-ynes involves trapping by nitriles and cyclization of the intermediates.11

MeOOC +

MeOOC

R

MeO

R'CN

AuCl–Et3P

R'

AgSbF6

N

ClCH2CH2Cl 85o

MeO

R

Ring closure is observed when 6-heptynals are exposed to the gold(I) salt.12 Silyl ketene amides and carbamates cyclize accordingly.13

Ph3PAuCl - AgOTf i-PrNHCy 70° CDCl3 (R = Me)

OHC

OHC

MeOOC

COOMe

R

MeOOC

COOMe

OHC Ph3PAuCl - AgOTf i-PrNHCy 70° CDCl3 (R = H)

TIPSO

O

O N

MeOOC

(Ph3P)AuCl–AgSbF6

COOMe

O N

82%

Cyclopentenes are formed from 1,5-enynes in moderate yields.14 Conversion of 1,2,4-alkatrienes into cyclopentadienes can be effected with the gold complex15 or PtCl2 (loc. cit.).

216

Gold(I) chloride – tertiary phosphine/silver salts

OSiMe3

O

OSiMe3 (Ph3P)AuCl AgSbF6 i-PrOH 23°

[Au] 50% Ph

OSiMe3

(Ph3P)AuCl

O

AgSbF6 i-PrOH 23°

Ph 65%

Participation of nucleophiles in the cyclization of enynes gives rise to functionalized products. Thus, substrates containing an allylic carbonate unit are transformed into derivatives of 4-cycloalkene-1,2-diols.16 Without an internally participatory group an enyne can incorporate an amine.17 O O

O

O R"

R

O

R'

(Ph3P)AuCl

+ R'NH2

R"

R"'

Ph

R

H

R R'

P

R"'

Z

O

AuCl–AgSbF6

H

AgSbF6

NHR' R

Z

THF 23o

Z = O, C(COOR)2, C(SO2Ph)2

In some situations, bicyclization of polyenynes leads to hydrocarbon products18 and arenes containing an allenyl group in a sidechain are subject to cycloisomerization.19 R (Ph3P)AuCl

C

R

AgSbF6

Ph MeOOC

Ph

0o

COOMe

MeOOC

COOMe

(PhO)3PAuCl

C

AgSbF6 CH2Cl2 23o

87%

Gold(I) chloride – tertiary phosphine/silver salts

217

Formation of a benzene ring is readily achieved from enynols and their esters when the oxygen functionality is propargylic.20,21 Ph

Ph (Ph 3P)AuCl–AgSbF6 23o

CH2Cl2

OH 84% R

R'

R R'

(Ph3P)AuCl–AgOTf ClCH2CH2Cl

R"

R"

Of synthetic interest is the assemblage of conjugated enynes and propargylic esters in the presence of AuCl and aromatization of the resulting cyclopropanes by (ArO)3PAuX.22 R2

X R2

R1

+

(ArO)3PAuCl

O O

R3

R2

R4

AuCl

O O

R3

AgSbF6

R1

4

R

H R3

R4

R2

(ArO)3PAuCl AgOTf

R1 R3

R4

Highly substituted a-pyrones are formed when propargyl propynoates are treated with (Ph3P)AuSbF6.23 The reaction proceeds via sequential Au-activation to induce [3,3]sigmatropic rearrangement and at the conjugated triple bond for the ensuing cyclization. O

Ar O

R'

O

O

(Ph3P)AuCl–AgSbF6 CH2Cl2

23o

Ar

R'

R R

218

Gold(I) chloride – tertiary phosphine/silver salts

While rearrangement of propargylic esters to allenyl esters is facile, denouement of such intermediates is highly dependent on the presence of other multiple CC bonds in juxtaposition.24,25 In any event, the generation of polycyclic compounds in one synthetic operation deserves serious consideration of the method for exploitation in the construction of signiﬁcant and complex target molecules. HH (Ph3P)AuCl–AgSbF6 CH2Cl2

OAc

OAc

98% Ph Ph (Ph3P)AuCl–AgSbF6 ClCH2CH2Cl

O OAc Ph

Ph Ph

(Ph3P)AuCl–AgSbF6

O

ClCH2CH2Cl

Ph

40o

O

75%

O

5-Alkoxyalk-6-en-1-ynes undergo cyclization to give cyclohepta-1,4-diene derivatives.26 The analogous siloxy enynes provide cyclohept-4-enones as major products. However, a change of the phosphine ligand to a more electron-rich version diverts the reaction pathway to the formation of products of a different type.27 O Et3SiO R3PAuCl

+

AgSbF6

H

H

CH2Cl2

8 :1

R = C6F5 R3P =

O

P

1 : 19 Ph

H

Gold(I) chloride – tertiary phosphine/silver salts

219

N-Allyl b-keto amides are found to cyclize in the presence of the Au(I) complex. Somewhat better results are obtained with that containing the biphenyldi-t-butylphosphine ligand.28 O

O O

(R3P)AuCl

O H

AgOTf PhMe

RN

RN R3P =

P Ph

Cyclodehydration of diols in which one of the hydroxyl groups is allylic shows another reaction pattern. When 2-alkenyl-6-alkyltetrahydropyrans are produced it favors the cisisomers.29 HO R

R'

OH

R

(Ph3P)AuCl

O

AgOTf CH2Cl2

n

R' n

The Au(I) catalyst system transforms 2,3-benzo-7-oxabicyclo[2.2.1]hept-2-ene into a tetralin-1,4-dication equivalent, as shown by its reaction with allylsilanes.30 (Ph3P)AuCl

O

R

+

SiMe3

R

AgSbF6 CH2Cl2

a,b;g,d-Dienals generate allyl cations extended by an auroxy substituent. Trapping in situ by allylsilanes and allylic alcohols provides structurally diversiﬁed products.31 O R

OH

R (Ph3P)AuCl

CHO

+

R

AgSbF6 CH2Cl2

OAuL Ph

H

SiMe3

R H

Ph

220

Gold(I) chloride – tertiary phosphine/silver salts

Through oxygen atom transfer acycarbenoids of gold are formed from homopropargyl phenyl sulfoxides. Cyclization ensues.32

S S Ph

S

(Ph3P)AuCl

O

AgSbF6

O

O

Ph

S

S

AgSbF6

O

N

N .. Au

LAu

S

O

O

Cl

Ar

S

O

ArS

AgSbF6

O R

N

R

N .. Au Cl

Rearrangements. Isomerization of propargylic alcohols to 1,3-transposed conjugated carbonyl compounds is catalyzed by (Ph3P)AuOTf and MoO2(acac)2.33 Allenyl oxomolybdates are likely involved as intermediates. Rearrangement intervenes in the hydration of a-silylated propargylic carboxylates.34

R' O

R' (Ph3P)AuCl

O

AgOTf H2O (1 equiv)

Si R

dioxane

O

O

Si

R O

Alkynes substituted at both propargylic positions, one with an ester and the other an epoxy ring are converted into enones, attendant by transposition of both unsaturated and oxygenation sites.35

Gold(I) chloride – tertiary phosphine/silver salts

221

R" O

O

O R'

R

R' O

(Ph3P)AuCl

R

AgSbF6 CH2Cl2

R

R' R' OCOR"

R

The ester unit of 1-(g-pivaloxypropargyl)cyclobutanols undergoes 1,3-shift to afford an allene that is activatable for cyclization.36 OH OH

AgOTf

C

O

O O

O 1

O

(Ph3P)AuCl

O

O

Nakamura, A., Tokunaga, M. TL 49, 3729 (2008). Li, Y., Yang, Y., Yu, B. TL 49, 3604 (2008). 3 Asao, N., Aikawa, H., Tago, S., Umetsu, K. OL 9, 4299 (2007). 4 Bender, C.F., Widenhoefer, R.A. CC 2741 (2008). 5 Yeom, H.-S., Lee, E.-S., Shin, S. SL 2292 (2007). 6 Lee, E.-S., Yeom, H.-S., Hwang, J.-H., Shin, S. EJOC 3503 (2007). 7 Barluenga, J., Fernandez, A., Satrustegui, A., Dieguez, A., Rodriguez, F., Fananas, F.J. CEJ 14, 4153 (2008). 8 Yang, T., Campbell, L., Dixon, D.J. JACS 129, 12070 (2007). 9 Zriba, R., Gandon, V., Aubert, C., Fensterbank, L., Malacria, M. CEJ 14, 1482 (2008). 10 Liu, X.-Y., Che, C.-M. ACIE 47, 3805 (2008). 11 Barluenga, J., Fernandez-Rodriguez, M.A., Garcia-Garcia, P., Aguilar, E. JACS 130, 2764 (2008). 12 Binder, J.T., Crone, B., Haug, T.T., Menz, H., Kirsch, S.F. OL 10, 1025 (2008). 13 Minnihan, E.C., Colletti, S.L., Toste, F.D., Shen, H.C. JOC 72, 6287 (2007). 14 Kirsch, S.F., Binder, J.T., Crone, B., Duschek, A., Haug, T.T., Liebert, C., Menz, H. ACIE 46, 2310 (2007). 15 Lee, J.H., Toste, F.D. ACIE 46, 912 (2007). 16 Lim, C., Kang, J.-E., Lee, J.-E., Shin, S. OL 9, 3539 (2007). 17 Leseurre, L., Toullec, P.Y., Genet, J.-P., Michelet, V. OL 9, 4049 (2007). 18 Lin, G.-Y., Yang, C.-Y., Liu, R.-S. JOC 72, 6753 (2007). 19 Tarselli, M.A., Gagne, M.R. JOC 73, 2439 (2008). 20 Grise, C.M., Rodrigue, E.M., Barriault, L. T 64, 797 (2008). 21 Dudnik, A.S., Schwier, T., Gevorgyan, V. OL 10, 1465 (2008). 22 Gorin, D.J., Watson, I.D.G., Toste, F.D. JACS 130, 3736 (2008). 23 Luo, T., Schreiber, S.L. ACIE 46, 8250 (2007). 24 Lemiere, G., Gandon, V., Cariou, K., Fukuyama, T., Dhimane, A.-L., Fensterbank, L., Malacria, M. OL 9, 2207 (2007). 25 Oh, C.H., Kim, A. SL 777 (2008). 26 Bae, H.J., Baskar, B., An, S.E., Cheong, J.Y., Thangadurai, D.T., Hwang, I.-C., Rhee, Y.H. ACIE 47, 2263 (2008). 2

222

Gold(I) chloride – tertiary phosphine/silver hexaﬂuoroantimonate-acetonitrile complex

27

Baskar, B., Bae, H.J., An, S.E., Cheong, J.Y., Rhee, Y.H., Duschek, A., Kirsch, S.F. OL 10, 2605 (2008). 28 Zhou, C.-Y., Che, C.-M. JACS 129, 5828 (2007). 29 Aponick, A., Li, C.-Y., Biannic, B. OL 10, 669 (2008). 30 Hsu, Y.-C., Datta, S., Ting, C.-M., Liu, R.-S. OL 10, 521 (2008). 31 Lin, C.-C., Teng, T.-M., Odedra, A., Liu, R.-S. JACS 129, 3798 (2007). 32 Shapiro, N.D., Toste, F.D. JACS 129, 4160 (2007). 33 Egi, M., Yamaguchi, Y., Fujiwara, N., Akai, S. OL 10, 1867 (2008). 34 Sakaguchi, K., Okada, T., Shimada, T., Ohfune, Y. TL 49, 25 (2008). 35 Cordonnier, M.-C., Blanc, A., Pale, P. OL 10, 1569 (2008). 36 Yeom, H.S., Yoon, S.J., Shin, S. TL 48, 4817 (2007).

Gold(I) chloride – tertiary phosphine/silver hexaﬂuoroantimonate-acetonitrile complex. Enol esters.1 Propargylic esters react with nucleophiles with attendant 1,2- or 1,3migration of the ester subunit, depending on the substitution pattern of the propargylic site. R' O O

+

O COOMe

R R

R

(MeCN)AuSbF 6

OCOR' COMe

R

P

COOMe Ph

R' O

COOMe OCOR'

O

+

O

O

COOMe

R

R

Cyclization. Allylic triorganostannyl and acetoxy groups at the two termini of a chain are simultaneously detached in the presence of R3PAu(MeCN)SbF6. In the process the remainder skeleton forms a ring.2 R

R

SnBu3 (MeCN)AuSbF 6

Z OAc

Z

P Ph

t-Butyl N-alkynylcarbamates cyclize to give imidazolones with loss of the t-butyl group.3 1

Amijs, C.H.M., Lopez-Carrillo, V., Echavarren, A.M. OL 9, 4021 (2007). Porcel, S., Lopez-Carrillo, V., Garicia-Yebra, C., Echavarren, A.M. ACIE 47, 1883 (2008). 3 Istrate, F.M., Buzas, A.K., Jurberg, I.D., Odabachian, Y., Gagosz, F. OL 10, 925 (2008). 2

Gold(III) chloride

223

Gold(III) chloride. O-Trimethylsilyl cyanohydrins. Derivatization of ketones and aldehydes is catalyzed by AuCl3 at room temeperature.1 Insertion by nitrene. Formation of ArNHNs from arenes and PhIvNNs is mediated by AuCl3. A secondary benzylic CZH bond is also reactive (e.g., 1,3,5-triisopropylbenzene gives two kinds of nitrene insertion products, and the benzylic amine derivative is predominant in a 3 : 2 ratio to the arylamine isomer.)2 Cyclization. Intramolecular addition of a hydroxy group to an allene unit results in cyclic ethers. Methoxymethyl ethers are also reactive but different regioselectivity has been noted.3

H

HO

OTBS AuCl 3

NR

O

C

OTBS

O H

CH2Cl2

H NR

O

MOMO O

H

OCOAr

NR

AuCl 3 CH2Cl2

C

O H

OCOAr H NR

O

1-Bromoalka-1,2-dien-4-ones afford b-bromofurans. With these substrates AuCl3 as well as AuCl are serviceable catalysts. However, there exists a remarkable ligand effect pertaining the employment of (Ph3P)AuX, with X ¼ BF4 vs. X ¼ OTf.4 a

Br

Br

[Au]

C R O

Br

–

+ O

R

O

R

O

R

Br b

a = (Ph3P)AuOTf b = AuCl, AuCl3, (Ph 3P)AuBF 4

Substitution. The geminal functional groups of 1-arenesulfonylcyclopropanols are both replaced in an AuCl3-catalyzed reaction with amines and 1-alkynes in water.5 It constitutes a new access to the special kind of propargylic amines. Direct conversion of allylic alcohols to the corresponding amines is also accomplished on treatment with AuCl3 in MeCN at room temperature.6

224

Gold(III) chloride – silver triﬂate

Quinoline synthesis. 2,4-Disubstituted quinolines are synthesized in one operation from arylamines, aldehydes, and 1-alkynes. A mixture of AuCl3 and CuBr is used to promote the condensation. The effectiveness of AuCl3 to transform N-propargylarylamines to quinolines at room temperature has been independently veriﬁed.7

X H2N

X

AuCl3–CuBr

N

MeOH 60o

+

Ar

Ar'

Ar CHO

Ar'

Benzyl ethers. Addition of ROH to styrenes to provide secondary benzyl ethers by Au(III) salts alone is not practical because Au(III) ion is readily reduced to the catalytically inactive Au(0) species. The problem is solved by using an AuCl3 – CuCl2 combination.8 1

Cho, W.K., Kang, S.M., Medda, A.K., Lee, J.K., Choi, I.S., Lee, H.-S. S 507 (2008). Li, Z., Capretto, D.A., Rahaman, R.O., He, C. JACS 129, 12058 (2007). 3 Alcaide, B., Almendros, P., del Campo, T.M. ACIE 46, 6684 (2007). 4 Xia, Y., Dudnik, A.S., Gevorgyan, V., Li, Y. JACS 130, 6940 (2008). 5 Liu, J., An, Y., Jiang, H.-Y., Chen, Z. TL 49, 490 (2008). 6 Guo, S., Song, F., Liu, Y. SL 964 (2007). 7 Xiao, F., Chen, Y., Liu, Y., Wang, J. T 64, 2755 (2008). 8 Zhang, X., Corma, A. CC 3080 (2007). 2

Gold(III) chloride – silver triﬂate. Cyclization. Allenylmalonic esters undergo cyclization in HOAc, leading to dihydroa-pyrones.1 Exposure of 1-aroxy-2,3-epoxypropanes to AuCl3 –AgOTf in dichloroethane leads to chroman-3-ols. A critical ligand has been identiﬁed.2 MeO

O

MeO

Ar

O

Ar

AuCl3–AgOTf

OMe

OH

ClCH2CH2Cl 50°

O

OMe

O N

N S

N Ph

o-Alkynylarylamines and 1-alkynes are combined to generate N-(2-alkenyl)indoles.3 R + NH2

R'

R

AuCl 3 AgOTf

N R'

Gold(I) triﬂimide – azolecarbene

225

In a single step alkynones are transformed into cyclic conjugated ketones.4 This reaction does not go through hydration. O AuCl3–AgOTf

O

PhMe 100°

R

R R'

O AuCl3–AgOTf

O R

R'

PhMe 100°

R 1

Piera, J., Krumlinde, P., Stru¨bing, D., Ba¨ckvall, J.-E. OL 9, 2235 (2007). Liu, Y., Li, X., Lin, G., Xiang, Z., Xiang, J., Zhao, M., Chen, J., Yang, Z. JOC 73, 4625 (2008). 3 Zhang, Y., Donahue, J.P., Li, C.-J. OL 9, 627 (2007). 4 Jin, T., Yamamoto, Y. OL 9, 5259 (2007). 2

Gold(I) cyanide. Isoﬂavanones. With AuCN –Bu3P to catalyze the combination of salicyladehydes and ethynylarenes, a redox transformation that proceeds via hydroauration of the alkynes by acylaurium hydrides eventually results in the formation of isoﬂavanones.1 O

O Ar H

+

OH

Ar

AuCN–Bu3P PhMe 150°

O

1

Skouta, R., Li, C.-J. ACIE 46, 1117 (2007).

Gold(III) oxide. Cycloisomerization. 4-Alkynoic acids cyclize to give g-alkylidene-g-butyrolactones under the inﬂuence of Au2O3.1 1

Toullec, P.Y., Genin, E., Antoniotti, S., Genet, J.-P., Michelet, V. SL 707 (2008).

Gold(I) triﬂimide – azolecarbene. Rearrangement. 2-Pivaloxy-1,3-dienes are formed by treatment of the corresponding propargylic esters with the Au(I) complex.1

226

Gold(I) triﬂimide – azolecarbene

OPiv

AuNTf 2

R

R'

R'

R N

OPiv

N ..

Oxygen atom transfer is observed in the reaction of homopropargyl sulfoxides.2 Formation of the 1,3-dicarbonyl unit from homopropargyl sulfoxides that contain a distal propargylic OH also engenders a group migration. O S

R AuNTf 2

S

N

Cl

R'

R Cl

HO

R'

N

O

OH

..

For cycloisomerization of a-alkynyl-b-keto esters the use of Tf2NAu in conjunction with very bulky tris[(triarylsilyl)ethynyl]phosphine ligands, remarkable rate enhancements are observed.3 The effect is attributable to the cavity environment created by the ligand to keep the nucleophilic center and the Au-activated triple bond of the substrate close. Cycloaddition. 1-Alkynyl-1-cyclopropyl ketones generate cyclic 1,3-dipolar species and their cycloaddition with vinyl ethers is followed by ring size regulation of the cycloadducts (expansion of the 3-membered ring and contraction of the 6-membered ring) and demetallation.4 O

R

OEt

O R'

AuNTf 2

R

+ N

H

R'

N ..

Equally interesting is trapping by carbonyl compounds, imines, and indoles, leading to polycycles containing a furan ring.5

R"

R" ..

N N

X

R' R

O

R"

AuNTf 2

[Au] X

R

R' O

R' R

O

Graphite

227

1

Li, G., Zhang, G., Zhang, L. JACS 130, 3740 (2008). Li, G., Zhang, L. ACIE 46, 5156 (2007). 3 Ochida, A., Ito, H., Sawamura, M. JACS 128, 16486 (2006). 4 Li, G., Huang, X., Zhang, L. JACS 130, 6944 (2008). 5 Zhang, G., Huang, X., Li, G., Zhang, L. JACS 130, 1814 (2008). 2

Gold(I) triﬂimide – triarylphosphine complex. Rearrangement. Rearrangement of propargylic esters as promoted by (Ph3P)AuNTf2 affords a-iodinated enones in the presence of NIS and a solvent system of acetone and water (800 : 1) at 08.1 Esters of allenyl carbinols give 2-acyloxy-1,3-dienes on treatment with AuNTf2, which is complexed to (20 ,40 ,60 -triisopropyl-2-biphenyl)dicyclohexylphosphine.2 An aza-Claisen rearrangement is implicated in the transformation of N-geranyl-N-(pent2-en-4-yn-1-yl)-p-toluenesulfonamide into an N-tosylpyrrole.3

Ts

F3C

Ts N

N

AuNTf 2

Ts N

[Au]

P 3

CH2Cl2

91%

3-Allylbenzosiloles are readily prepared from [(o-alkynyl)aryl]allylsilanes.4

R AuNTf 2

R Si

P

CH2Cl2

Si

Ph

1

Yu, M., Zhang, G., Zhang, L. OL 9, 2147 (2007). Buzas, A.K., Istrate, F.M., Gagosz, F. OL 9, 985 (2007). 3 Istrate, F.M., Gagosz, F. OL 9, 3181 (2007). 4 Matsuda, T., Kadowaki, S., Yamaguchi, Y., Murakami, M. CC 2744 (2008). 2

Graphite. Substitution. Alkylation of alcohols and arenes by alkyl halides (including benzyl halides) is easily performed on heating (116–1308) the components with graphite, either neat or in PhCl.1 1

Sereda, G.A., Rajpara, V.B., Slaba, R.L. T 63, 8351 (2007).

228

Grignard reagents

Grignard reagents. X/magnesium exchange. The general method for preparing Grignard reagents by the exchange method using i-PrMgCl as applied to 3-substituted 1,2,5-tribromobenzenes in THF at – 408 is dependent on the nature of the substituent R.1 Preference for exchange of the 1-Br atom when R ¼ H, Me, OMe; and of the 2-Br atom when R ¼ F, Cl, CF3, CN. 1-Chlorocyclopropyl phenyl sulfoxide undergoes exchange reaction to afford 1-chlorocyclopropylmagnesium chloride (a magnesium carbenoid) that reacts with N-lithioarylamines to give o-cyclopropylarylamines.2 O S Ph

i-PrMgCl

Cl

Cl

R'

ArN(R)Li

MgCl HNR

Selective insertion of magnesium carbenoid to a cyclic CZH bond instead of one at the a-position of an ester group is perhaps quite unexpected.3

Cl SOPh COOEt

i-PrMgCl PhMe –78 ~ 0°

COOEt

96%

Br/Mg exchange converts 1,2-dibromocyclopentene into the b-bromoalkenylmagnesium chloride (LiCl complex), which reacts normally with carbonyl compounds. It is possible to peform a copper-mediated coupling at the b-carbon site while retaining the CZMgCl unit.4 Br Br

i-PrMgCl · LiCl 25°

MgCl · LiCl Br

MgCl · LiCl RMgCl CuCN

R R'COCl ZnCl2, CuCN

O R' R

Addition reactions. RMgCl adds to pyridine N-oxides at C-2 to generate dienal oximes.5 When the crude products are heated with Ac2O, homologated pyridines result.6

Grignard reagents

R"

R" +

RMgX

229

THF

N O

R

R'

R'

NOH

Neighboring group-direction determines the Grignard reaction of 2-methoxy-N-methylsuccinimide. On the other hand, a bulky TBSO group exerts its regiochemical inﬂuence.7 MeO

MeO MeMgCl(OMe2)2

O

O

N Me

N Me

HO

TBSO

TBSO MeMgCl(OMe2)2

O

O

OH

O

N Me

O

N Me

At low temperatures and over very short reaction time Grignard reaction yields ketone from esters of polyﬂuorinated carboxylic acids. The ketones are susceptible to reduction by RR0 CHOMgX at a higher temperature.8 O f

R

R' O

O

RMgX low temp.

R"

f

R

R'

+

XMg

R

O

R"

higher temp.

H

OH

f

R

R

Diaryl ketones are formed in the Grignard reaction of ArCHO with Ar0 MgX LiCl, when PhCHO is added during workup.9 A redox process (Mg-Oppenauer oxidation of the halomagnesium diarylmethoxides) is involved. o-Aminoaryl chloromethyl ketones furnish 2-substituted indoles on reaction with RMgX (or RLi), as a consequence of 1,2-aryl migration after the addition step.10 O Cl +

R

RMgX

NH2 Cl

Cl

N H

230

Grignard reagents

Conjugate addition of the R group from RMgX to a,b-unsaturated carboxylic acids and amides is observed when mixed with three equivalents of MeLi in THF. The methyl group of MeLi does not compete.11 Alkynylmagnesium bromides add to organoazides to form 4-(1,2,3-triazolyl)magnesium bromides. 1,4,5-Trisubstituted 1,2,3-triazoles are obtained after transmetallation (ZnCl2) and Negishi coupling.12 Substitution. (S)-Mesitylenesulﬁnimines are obtained from 1, through a double displacement sequence and reaction with aldehydes. The ﬁrst step is the Grignard reaction with MesMgBr.13 MgBr

O O

S

NTs

O THF, –78°;

+

S

(Me3Si)2NLi RCHO

Ph

R

(1)

99% ee

Desulfurization and methylenation of lithiated sultams by ICH2MgCl releases homoallylic amines.14

MeLi

NBn

NHBn

ICH2MgCl

S O O

Reaction of a-chloroalkyl t-butanesulﬁnylimines with RMgX affords cyclopropylamine derivatives. But different products are obtained from the reaction involving allylmagnesium chloride.15

XMg R R R'MgX

N

R R

S

N

S

O

HN R

Cl

S

O

R'

R

O MgCl

Cl

XMg R R

N

S

O N

Cl

S

O

Grignard reagents/cerium(III) chloride

231

Tricyclopropylbismuth and dicyclopropylbismuth chloride are obtained by reaction of cyclopropylmagnesium bromide with BiCl3 according to the required stoichiometry. These organobismuth compounds are useful for N-cyclopropylation of lactams such as phenanthridinone.16 N-Bromomagnesium enamines are formed on treatment of cyclohexanone imines of N,N-diethylethanamine with mesitylmagnesium bromide. These highly nucleophilic species react with even secondary alkyl ﬂuorides.17 1

Menzel, K., Mills, P.M., Frantz, D.E., Nelson, T.D., Kress, M.H. TL 49, 415 (2008). Yamada, Y., Miura, M., Satoh, T. TL 49, 169 (2008). 3 Ogata, S., Saitoh, H., Wakasugi, D., Satoh, T. T 64, 5711 (2008). 4 Despotopoulou, C., Bauer, R.C., Krasovskiy, A., Mayer, P., Stryker, J.M., Knochel, P. CEJ 14, 2499 (2008). 5 Andersson, H., Wang, X., Bjo¨rklund, M., Olsson, R., Almqvist, F. TL 48, 6941 (2007). 6 Andersson, H., Almqvist, F., Olsson, R. OL 9, 1335 (2007). 7 Ye, J.-L., Huang, P.-Q., Lu, X. JOC 72, 35 (2007). 8 Yamazaki, T., Terajima, T., Kawasaki-Takasuka, T. T 64, 2419 (2008). 9 Kloetzing, R.J., Krasovskiy, A., Knochel, P. CEJ 13, 215 (2007). 10 Pei, T., Chen, C.-Y., Dormer, P.G., Davies, I.W. ACIE 47, 4231 (2008). 11 Kikuchi, M., Niikura, S., Chiba, N., Terauchi, N., Asaoka, M. CL 36, 736 (2007). 12 Akao, A., Tsuritani, T., Kii, S., Sato, K., Nonoyama, N., Mase, T., Yasuda, N. SL 31 (2007). 13 Sasraku-Neequaye, L., MacPherson, D., Stockman, R.A. TL 49, 1129 (2008). 14 Rogachev, V.O., Merten, S., Seiser, T., Kataerva, O., Matz, P. TL 49, 133 (2008). 15 Denolf, B., Mangelinckx, S., To¨rnroos, K.W., De Kimpe, N. OL 9, 187 (2007). 16 Gagnon, A., St-Onge, M., Little, K., Duplessis, M., Barabe, F. JACS 129, 44 (2007). 17 Hatakeyama, T., Ito, S., Yamane, H., Nakamura, M., Nakamura, E. T 63, 8440 (2007). 2

Grignard reagents/cerium(III) chloride. Addition to carbonyl group. The decrease in basicity of the RMgX–CeCl3 system helps maintain the normal nucleophilic addition of the organometallic reagents, while suppressing enolization of carbonyl substrates.1 OH

O

O

RMgX

O

CeCl3

R

RMgX

OH

OM O

OH R

1

Mlinaric-Majerski, K., Kragol, G., Ramljak, T.S. SL 405 (2008).

232

Grignard reagents/chromium(II) salts

Grignard reagents/chromium(II) salts. Addition. Grignard reagents such as PhMgBr add to alkynes to give alkenylmagnesium bromides when CrCl2 and t-BuCOOH are present as catalysts. The adducts have a cis-conﬁguration.1 1

Murakami, K., Ohmiya, H., Yorimitsu, H., Oshima, K. OL 9, 1569 (2007).

Grignard reagents/cobalt(II) salts. Couplings. In the presence of CoCl2 and 1,3-diarylimidazolium chloride, N-arylN-(2-iodoethyl)-p-toluenesulfonamie reacts with some RMgCl to afford 3-substituted N-toylpyrrolidines.1

Ts N

Ts N

CoCl2

+

R

MgCl ArN

I

NAr

R

Cl

1

Someya, H., Ohmiya, H., Yorimitsu, H., Oshima, K. OL 9, 1565 (2007).

Grignard reagents/copper salts. Substitution. N,N-Diorganohydroxylamine benzoates react with RMgX in the presence of CuCl2 to provide RNR0 R00 .1 Alkylation of cyclopentadienylmagnesium bromide with tertiary alkyl halides occurs when Cu(OTf)2 is present.2 The SN20 substitution of allylic picolinates is subject to chelation control.3

N O

O R'

+

ArMgBr

Ar

CuBr · Me2S

R

R'

R

A method for synthesizing tetrahydropyridines involves Cu-catalyzed ring opening of N-tosylaziridnes with 2-(1,3-dioxan-2-yl)magnesium bromide.4 2-Alkylideneaziridines are attacked by RMgX at C-3 to generate iminomagnesium halides that can be alkylated.5

Grignard reagents/copper salts

O

O

NTs

+

O

CuBr · Me2S

Ts N

O

R

NHTs

THF

MgBr

233

R R MgX R BnN

R BnN

R

+

CuI

R'MgX

THF

R

BnN

R"X

R R"

R R'

R'

Ring-fused b-lactones open to deliver trans-2-organocycloalkanecarboxylic acids.6

H

H

R

RMgCl – CuX

O

n

n COOH

O

Addition reactions. As an alternative to the Baylis– Hillman approach (Z )-2-hydroxyalkyl-2-alkenoic esters are assembled from propynoic esters via a Cu(I)-catalyzed Grignard reaction and trapping with RCHO.7

Me3SiO

COOEt

OEt

RMgBr

C

Me3SiOTf

R

OH R'CHO

COOEt

R' H

R

Allylic and allenyl Grignard reagents are available by conjugate carbomagnesiation of 1,3-dienes and 1,3-enynes, respectively.8

R'

R' +

RMgX

Li2CuCl4

R

MgX R'

R' R' +

RMgX

R'

Li2CuCl4

R

C

MgX

Attack of Grignard reagents on N-allyl-N-alkynyl-N-arenesulfonamides (CuBr . SMe2 being present) prompts a [3,3]sigmatropic rearrangement, producing a-allyl nitriles.9

234

Grignard reagents/iron salts

SO2Ar Ph

N + RMgBr

CuBr · SMe2

R

DME – Et2O Δ

Ph

CN

Coupling reactions. Various Grignard reagents couple with RX (reactivity proﬁle: X ¼ Cl , F , OMs , OTs , Br) in the presence of CuCl2 and a minute amount of 1-phenylpropyne. Coupling reaction with unsymmetrical dichloroalkanes selectively replaces the primary chloride.10 Esters are formed by coupling of RMgX with ClCOOR0 .11 1

Campbell, M.J., Johnson, J.S. OL 9, 1521 (2007). Sai, M., Someya, H., Yorimitsu, H., Oshima, K. OL 10, 2545 (2008). 3 Kiyotsuka, Y., Acharya, H.P., Hyodo, T., Kobayashi, Y. OL 10, 1719 (2008). 4 Pattenden, L.C., Adams, H., Smith, S.A., Harrity, J.P.A. T 64, 2951 (2008). 5 Montagne, C., Shiers, J.J., Shipman, M. TL 47, 9207 (2006). 6 Zhang, W., Matla, A.S., Romo, D. OL 9, 2111 (2007). 7 Mueller, A.J., Jennings, M.P. OL 10, 1649 (2008). 8 Todo, H., Terao, J., Watanabe, H., Kuniyasu, H., Kambe, N. CC 1332 (2008). 9 Yasui, H., Yorimitsu, H., Oshima, K. CL 36, 32 (2007). 10 Terao, J., Todo, H., Begum, S.A., Kuniyasu, H., Kambe, N. ACIE 46, 2086 (2007). 11 Bottalico, D., Fiandanese, V., Marchese, G., Punzi, A. SL 974 (2007). 2

Grignard reagents/iron salts. Isomerization. Secondary alkylmagnesium halides are transformed into the primary isomers upon treatment with FeCl3, CuBr and Bu3P in THF at – 258.1 Coupling reactions. Heteroatom-directed arylation of 2-arylpyridines with ArMgBr and (tmeda)ZnCl2 also requires Fe(acac)3, 1,10-phenanthroline, and an electron acceptor (e.g., 1,2-dichloro-2-methylpropane).2 A redox cycle of the iron species is set up during the reaction. It is further shown that TMEDA and hexamethylenetetramine have cooperative effect on Fe(acac)3.3

+ N

ArMgBr

Fe(acac) 2 , (tmeda)ZnCl2

Cl

N

Cl THF

0o

Ar

N

N

Demetallative dimerization occurs when ArMgX are exposed to FeCl3 in dry air at room temperature. Conjugated dienes are similarly prepared from alkenylmagnesium halides. (For oxidative homocoupling of alkynyl and benzyl Grignard reagents, MnCl2 2LiCl is used as the catalyst.)4

Grignard reagents/iron salts

235

Sulfonyl chlorides are totally defunctionalized (with loss of SO2 also) during coupling with Grignard reagents.5 Alkenylmagnesium bromides and alkyl halides (bromides and iodides) are coupled in the presence of FeCl3 and TMEDA,6 whereas for the formation of ArMgBr and RX a complex derived from FeCl3 and 1 has been identiﬁed.7

OHHO ArMgX + RX

N

FeCl3

Ar-R

(1)

O

(1) Addition reactions. cis-Addition of ArMgBr to alkynes leads to styrylmagnesium bromides. Regioselective generation of stilbene derivatives from arylalkynes is observed.8 2,3-Alkadienoic esters undergo conjugate addition with RMgX –Fe(acac)3.9 R R

Fe(acac)3 / THF 60°

+

ArMgBr

Ar'

N

Ar

Ar'

N

MgBr

..

R'

R' Fe(acac) 3

RMgX +

C

R'"OOC

PhMe –78°

R"

R

COOR"'

R"

Elimination.10 Conjugated enynes and styrenes are formed from b-hydroxy sulﬁdes that are derived from 2-alkynyl- and 1-aryl-1,3-dithiolanes. The reaction is considered as an alternative method to McMurry coupling. R" HO

R"' S

R" SBu

Fe(acac) 3

R R' 1

R"'

MeMgI

R R'

Shirakawa, E., Ikeda, D., Yamaguchi, S., Hayashi, T. CC 1214 (2008). Norinder, J., Matsumoto, A., Yoshikai, N., Nakamura, E. JACS 130, 5858 (2008). 3 Cahiez, G., Habiak, V., Duplais, C., Moyeux, A. ACIE 46, 4364 (2007). 2

236

Grignard reagents/manganese salts

4

Cahiez, G., Moyeux, A., Buendia, J., Duplais, C. JACS 129, 13788 (2007). Volla, C.M.R., Vogel, P. ACIE 47, 1305 (2008). 6 Guerinot, A., Reymond, S., Cossy, J. ACIE 46, 6521 (2007). 7 Chowdhury, R.R., Crane, A.K., Fowler, C., Kwong, P., Kozak, C.M. CC 94 (2008). 8 Yamagami, T., Shintani, R., Shirakawa, E., Hayashi, T. OL 9, 1045 (2007). 9 Lu, Z., Chai, G., Ma, S. JACS 129, 14546 (2007). 10 Huang, L.-F., Chen, C.-W., Luh, T.-Y. OL 9, 3663 (2007). 5

Grignard reagents/manganese salts. Coupling. Grignard reagents couple with heteroaryl chlorides proceeds in the presence of MnCl2.1 1

Rueping, M., Ieawsuwan, W. SL 247 (2007).

Grignard reagents/nickel complexes. Substitution. Certain alkoxy group of an alkyl naphthyl ether is susceptible to replacement on reaction with MeMgI under the inﬂuence of Ni(II).1 Interestingly, in the presence of (dppf)NiCl2 the sidechain methoxy group of 6-methoxy-2-naphthylmethyl methyl ether shows a higher reactivity.2

R=H

HO

OMe + MeMgI RO

(Cy3P)2NiCl2 R = Ph, allyl (dppf)NiCl2 DPPF

OMe

MeO

MeO + MeMgX

Ni(acac)2 Cy3P, DPPF

Kumada coupling. A report of biaryl synthesis from ArMgBr and Ar0 Cl highlights the use of a Ni carbenoid (1).3 Both bis(h3-allyl)nickel and palladium complexes are also useful catalysts for the cross-coupling.4

Grignard reagents/palladium complexes

N N

237

N Ni

N

ArMgBr + Ar'Cl

N

N

(1)

THF, 25 o

2PF6

(1)

Ar–Ar'

1

Guan, B.-T., Xiang, S.-K., Wu, T., Sun, Z.-P., Wang, B.-Q., Zhao, K.-Q., Shi, Z.-J. CC 1437 (2008). Guan, B.-T., Xiang, S.-K., Wang, B.-Q., Sun, Z.-P., Wang, Y., Zhao, K.-Q., Shi, Z.-J. JACS 130, 3268 (2008). 3 Xi, Z., Liu, B., Chen, W. JOC 73, 3954 (2008). 4 Terao, J., Naitoh, Y., Kuniyasu, H., Kambe, N. CC 825 (2007). 2

Grignard reagents/palladium complexes. Coupling. In polychloroarenes the chlorine atom ortho to a protic group (if such is present) is selectively replaced by R of RMgX.1 One possible explanation of the phenomenon assigns the importance of Mg coordination to facilitate the oxidative addition of Pd to the CZCl bond. Y

Y Cl + Cl

R

(dba)3Pd2

RMgX

Cy3P THF

Cl

Coupling ascribing to more clearcut directing effect is the selective reaction with the ortho-Br of an alkali metal salt of 2,5-dibromobenzoic acid in the presence of (dba)3Pd2.2 Kumada coupling at low temperature is accomplished by using (dba)2Pd with the 20 -dimethylaminobiphenyl(dicyclohexyl)phosphine ligand.3 Biaryl synthesis through Kumada coupling has employed a recyclable catalyst in which PdCl2 is anchored in a mesoporous silica with an appended bipyridyl unit.4 It also has addressed the steric hindrance issue. Choice of ligands appears to be important. One report describes the use of a PdCl2 complex of both 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene and 3-chloropyridine,5 another indicates the effectiveness of (t-Bu2POH)2PdCl2.6 1

Ishikawa, S., Manabe, K. OL 9, 5593 (2007). Houpis, I.N., van Hoeck, J.-P., Tilstam, U. SL 2179 (2007). 3 Martin, R., Buchwald, S.L. JACS 129, 3844 (2007). 4 Tsai, F.-Y., Lin, B.-N., Chen, M.-J., Mou, C.-Y., Liu, S.-T. T 63, 4304 (2007). 5 Organ, M.G., Abdel-Hadi, M., Avola, S., Hadei, N., Nasielski, J., O’Brien, C.J., Valente, C. CEJ 13, 150 (2007). 6 Wolf, C., Xu, H. JOC 73, 162 (2008). 2

238

Grignard reagents/silver salts

Grignard reagents/silver salts. Coupling. In the presence of catalytic amounts of AgNO3 the coupling of ArCH2MgBr with alkyl halides (reactivity: tertiary . secondary) in ether takes place at room temperature.1 Zero-valent Ag entity is produced to donate a single electron to RX, generating an alkyl radical that is to combine with Ag(0); AgX that also emerges reacts with ArCH2MgBr and the ﬁrst catalytic cycle is completed when the two different organosilver species couple. 1

Someya, H., Ohmiya, H., Yorimitsm, H., Oshima, K. OL 10, 969 (2008).

Grignard reagents/titanium(IV) compounds. Kulinkovich reaction. Optimal conditions for the preparation of 1,2-disubstituted cyclopropanols from methyl esters in ether or THF involve 1 equivalent of (i-PrO)4Ti, 1.5 equivalent of MeMgX and 1.5 equiv. of RCH2CH2MgX.1 RCOOMe +

MgX

MeMgX

R

OH

(i-PrO)4Ti

R'

R'

Intramolecular vinyl transfer from a vinyl ether to an ester has been reported.2

COOMe

c-C6H11MgX (i-PrO)4Ti

O

OH

OH

Reaction involving 3-butenylmagnesium bromide shows substrate-dependence. 1,2Dicarbanion character and 1,4-dicarbanion character are manifested toward ester and nitrile groups, respectively.3

PhCN

Ph

NH2

MgBr + (i-PrO)4Ti

COOEt CN

NH O

Reductive coupling. Cross coupling of allylic alcohols with alkynes leads to 1,4dienes using (i-PrO)3TiCl and c-C5H9MgCl.4 Allenyl carbinols react without loss of the hydroxyl group.5

Grignard reagents/titanium(IV) compounds

OLi +

R

R

R"'

c-C5H9MgCl

OH

+

C

R"' R" R"

OH

R"'

c-C5H9MgCl

R"'

(i-PrO)3TiCl

R"

R

R'

(i-PrO)3TiCl

R"

R'

R

R

OH

239

R" +

C

R"'

R"'

c-C5H9MgCl (i-PrO)3TiCl

R"

R

Cross-coupling of alkenes and alkynes proceeds via titanacyclopentenes, therefore protonolysis afford alkenes in which the two substituents originally attached to the sp-carbon atoms become cis-related.6 Imines and homallylic alcohols also combine stereoselectively to give 1,5-amino alcohols, which are valuable precursors of piperidines.7 OH c-C5H9MgCl

BnN

[M]

(i-PrO)3TiCl

Ph

OH

NBn

NHBn Ph

Ph

Workup by trapping with CO2 diverts the product formation to conjugated g-lactams.8

OLi

NBn +

(i-PrO)3TiCl PhMe –78° ~ –30°

R R'

O

c-C5H9MgCl

BnN

O Ti

R

CO2

R'

90o

OH

O BnN R 1

Kulinkovich, O.G., Kananovich, D.G. EJOC 2121 (2007). Garnier, J.-M., Lecornue´, F., Charnay-Pouget, F., Ollivier, J. SL 2827 (2007). 3 Bertus, P., Menant, C., Tanguy, C., Szymoniak, J. OL 10, 777 (2008). 2

R'

240

Grignard reagents/zirconium compounds

4

Kolundzic, F., Micalizio, G.C. JACS 129, 15112 (2007). Shimp, H.L., Hare, A., McLaughlin, M., Micalizio, G.C. T 64, 3437 (2008). 6 Reichard, H.A., Mecalizio, G.C. ACIE 46, 1440 (2007). 7 Takahashi, M., Micalizio, G.C. JACS 129, 7514 (2007). 8 McLaughlin, M., Takahashi, M., Micalizio, G.C. ACIE 46, 3912 (2007). 5

Grignard reagents/zirconium compounds. Addition to ketones. Participation of the cyclic ether moiety in Cp2ZrCl2-catalyzed carbomagnesiation of terminal alkenes, e.g., (1), has been observed.1 Grignard reagents resulting from the transformation contain rather special structures. MgCl (CH2)m O

(CH2)n

MgCl

m Cp2ZrCl2

n

OMgCl

(1) 1

Barluenga, J., Alvarez-Rodrigo, L., Rodriguez, F., Fananas, F.J. OL 9, 3081 (2007).

H Hafnium(IV) chloride. Michael reaction.1 Catalyzed by HfCl4, indoles and pyrroles undergo Michael reactions with enones at C-3, and C-2/C-5, respectively. The reaction of pyrazole and imidazole takes place at an N-atom. Sakurai reaction 1 Friedel –Crafts alkylation.2 Two Lewis-catalyzed reactions to generate 3,4,4-triaryl-1-butenes can be performed in sequence in one pot using HfCl4. For example, addition of an allylsilane to ArCHO is followed by alkylation of anisole or phenol. 1

Kawatsura, M., Aburatani, S., Uenishi, J. T 63, 4172 (2007). Sano, Y., Nakata, K., Otoyama, T., Umeda, S., Shiina, I. CL 36, 40 (2007).

2

Hexabutylditin. Condensation. Generation of stabilized free radicals from dithiocarbonate esters via CZS bond cleavage is promoted by Bu3SnSnBu3. By providing an alkene and a trapping agent, homologation of a carbon chain while performing functionalization, for example, carboazidation,1 is realized. S

OEt

Ph Si

S +

EtOOC

PhH

SO2N3

Ph Si

Bu3SnSnBu3

R

60o

R

OAc EtOOC

N3

OAc

N

By the same principle a synthesis of piperidones is achieved in one step.2 EtO

R'

S

R'

Bu3SnSnBu3

S

+ O

OR"

RZnBr

SO2Ph

O

N R OBn

NOBn 1

Chabaud, L., Landais, Y., Renaud, P., Robert, F., Castet, F., Lucarini, M., Schenk, K. CEJ 14, 2744 (2008). 2 Godineau, E., Landais, Y. JACS 129, 12662 (2007). Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 241

242

Hexaﬂuoroacetone

Hexaﬂuoroacetone. b-Hydroxycarboxamides. Selective amidation of b-hydroxyalkanoic acids is easily performed via formation and aminolysis of 2,2-bis(triﬂuoromethyl)-1,3-dioxan-4-ones.1 The heterocycles are obtained from condensation of the hydroxy acids with hexaﬂuoroacetone in the presence of N,N0 -diisopropylcarbodiimide. 1

Spengler, J., Ruiz-Rodriguez, J., Yraola, F., Royo, M., Winter, M., Burger, K., Albericio, F. JOC 73, 2311 (2008).

Hexakis[hydrido(triphenylphosphine)copper]. Ring expansion. 2-Allenyl-1,1-cyclopropanedicarboxylic esters are transformed into 3-methylenecyclopentenes on treatment with [(Ph3P)CuH]6 at room temperature in toluene containing a small amount of water.1 COOMe

COOMe

[(Ph3P)CuH]6

COOMe

R

PhMe (H2O)

C

COOMe

R

25o

1

Hiroi, K., Kato, F., Oguchi, T., Saito, S., Sone, T. TL 49, 3567 (2008).

Hexamethylenetetramine. Transesteriﬁcation. The title amine actively catalyzes transestericiation of b-keto esters.1 1

Ribeiro, R.S., de Souza, R.O.M.A., Vasconcellos, M.L.A.A., Oliveira, B.L., Ferreira, L.C., Aguiar, L.C.S. S 61 (2007).

Hydrazine hydrate. Hydrodechlorination.1 2,6-Dichloropurine is selectively transformed into 2-chloropurine by treatment with hydrazine and then heating with NaOH under essentially the Wolff –Kishner reduction conditions. Cl N

N Cl

+ N

N H

N2H4

Δ

N

N

NaOH

Cl

N

N H

100% 1

Uciti-Broceta, A., de las Infantas, M.J.P., Gallo, M.A., Espinosa, A. CEJ 13, 1754 (2007).

Hydrogen peroxide

243

Hydrogen ﬂuoride. Fragmentation. A moisture stable homoallylic ﬂuorosilane which shows electrophile and pronucleophile properties is available from a 3-hydroxysilolane. The fragmentation is induced by HF.1 Ph

Ph Si

Ph HF EtOH

Ph Si

Δ

F

HO 1

Sen, S., Purushotham, M., Qi, Y., Sieburth, S.M. OL 9, 4963 (2007).

Hydrogen ﬂuoride – antimony(V) ﬂuoride. Cyclization. Piperidines ﬂuorinated at C-3 and C-4 are accessible from diallylamine derivatives. Hydride and methyl shifts can intervene prior to capture of the carbocations by ﬂuoride ion.1 O

O

HF–SbF 5

N

N

F

F3 C

F3C

69%

1,1,1-Triﬂuoroalkanes.2 These substances can be obtained by treatment of 1,1-dichloroalkenes with HF –SbF5. 1

Vardelle, E., Gamba-Sanchez, D., Matin-Mingot, A., Jouannetaud, M.-P., Thibaudeau, S., Marrot, J. CC 1473 (2008). 2 Cantet, A.-C., Gesson, J.-P., Renoux, B., Jouannetaud, M.-P. TL 48, 5255 (2007).

Hydrogen peroxide. Oxidation. The oxidation of arylamines to give nitrosoarenes by H2O2 is catalyzed by PhSeSePh at room temperature.1 The unstable products are trapped with conjugated dienes. A synthesis of allenyl carbinols (in variable yields) involves treatment of 2-phenylselenyl-1,3-dienes with H2O2 and Et3N at room temperature.2 R

SePh

H2O2 –Et 3N

R C

THF

R'

R' HO

N-Oxidation of electron-deﬁcient pyridines is achieved by H2O2 in MeCN at 08 if it is activated by Tf2O (Na2CO3 to neutralize the acid).3

244

Hydrogen peroxide, acidic

Epoxidation. Conjugated carbonyl compounds are epoxidized with stoichiometric H2O2 and NaOH while employing tetrabutylammonium peroxydisulfate as catalyst.4 1

Zhao, D., Johansson, M., Ba¨ckvall, J.-E. EJOC 4431 (2007). Redon, S., Berkaoui, A.-L.B., Pannecoucke, X., Outurquin, F. T 63, 3707 (2007). 3 Zhu, X., Kreutter, K.D., Hu, H., Player, M.R., Gaul, M.D. TL 49, 832 (2008). 4 Yang, S.G., Hwang, J.P., Park, M.Y., Lee, K., Kim, Y.H. T 63, 5184 (2007). 2

Hydrogen peroxide, acidic. Oxidation. A protocol for oxidation of sulﬁdes to sulfoxides with H2O2 in EtOH includes Tf2O.1 The stepwise conversion of arylamines to nitrosoarenes and thence nitroarenes by H2O2 using heteropolyacids as catalyst has been reported.2 Iodination. Arenes are iodinated with electrophilic species generated in situ from NH4I with H2O2 in HOAc.3 1

Khodaei, M.M., Bahrami, K., Kairimi, A. S 1682 (2008). Tundo, P., Romanelli, G.P., Vazquez, P.G., Loris, A., Arico, F. SL 967 (2008). 3 Narender, N., Reddy, K.S.K., Mohan, K.V.V.K., Kulkarni, S.J. TL 48, 6124 (2007). 2

Hydrogen peroxide – metal catalysts. Oxidation. For promoting oxidation of sulﬁdes to sulfoxide by H2O2 metal catalysts now include HAuCl4 . 4H2O1 and a titanium complex2 derived from tris(3-t-butyl-2-hydroxybenzyl)amine. In the latter report good turnover while employing only 0.01 –1% of the catalyst has been observe. The molybdenum-alkyne complex CpMo(CO)3(CCPh) is converted into 1 to exert its catalytic activity during oxidation of arylamines to nitrosoarenes.3

O Mo O

Ph

O

(1) Alcohols are oxidized (to aldehydes and ketones) by H2O2 with catalytic quantitites of RuCl3 and 3-iodobenzoic acid.4 Sulfoxidation is catalyzed by a Fe(III)-corrolazine, and surprisingly the active oxidant is a ferric hydroperoxide species.5 Complete oxidation of thiols to sulfonic acids occurs on treatment with H2O2 and methyltrioxorhenium in MeCN at room temperature.6 To generate bromine in situ a mixture of HBr and KBr is oxidized by H2O2 in the presence of a catalytic amount of NH4VO3.7

Hydrosilanes

245

Epoxidation. To convert H2O2 into an epoxidizing agent for alkenes a mixture of FeCl3 . 6H2O, 2,6-pyridinedicarboxylic acid, and pyrrolidine in t-AmOH is added.8 A Pt salt, [(dppe)Pt(C6F5)(H2O)]OTf, is able to catalyze selective epoxidation of a monosubstituted (terminal) alkene with H2O2, without affecting an internal double bond.9 As catalysts for epoxidation, methyltrioxorhenium is modiﬁed by converting into the more stable 2.10 X

O

N H O

O

Re Me

O

(2) 1

Yuan, Y., Bian, Y. TL 48, 8518 (2007). Mba, M., Prins, L.J., Licini, G. OL 9, 21 (2007). 3 Biradar, A.V., Kotbagi, T.V., Dongare, M.K., Umbarkar, S.B. TL 49, 3616 (2008). 4 Yusubov, M.S., Gilmkhanova, M.P., Zhdankin, V.V., Kirschning, A. SL 563 (2007). 5 Kerber, W.D., Ramdhanie, B., Goldberg, D.P. ACIE 46, 3718 (2007). 6 Ballistreri, F.P., Tomaselli, G.A., Toscano, R.M. TL 49, 3291 (2008). 7 Moriuchi, T., Yamaguchi, M., Kikushima, K., Hirao, T. TL 48, 2667 (2007). 8 Anilkumar, G., Bitterlich, B., Gelalcha, F.G., Tse, M.K., Beller, M. CC 289 (2007). 9 Colladon, M., Scarso, A., Sgarbossa, P., Michelin, R.A., Strukul, G. JACS 129, 7680 (2007). 10 Zhou, M.-D., Zhao, J., Li, J., Yue, S., Bao, C.-N., Mink, J., Zang, S.-L., Ku¨hn, F.E. CEJ 13, 158 (2007). 2

Hydrosilanes. Reduction. Intramolecular delivery of a hydride ion to an incipient carbocation can occur with a hydrosilane.1

H R MsO

H

H R

O O Si H

R Zn(OAc)2 (CF3)3CHOH

H

R

O O Si R'O

Using the siloxane [Me2Si(H)]2O under catalysis by (i-PrO)4Ti, phosphine oxides are readily deoxygenated.2 The diiodorhodium acetate complexed to two benzimidazolylcarbene units (1) is a useful catalyst for hydrosilylation of ketones,3 although a simpler system involves (EtO)2SiMeH and Fe(OAc)2.4

246

Hydrosilanes

A method for reductive amination of aldehydes calls for using 2 (prepared from [(cod)IrCl]2) as catalyst.5 Catalyzed by FeSO4 . 7H2O and using (Me3Si)2NH and Cbz-Cl to conjugate with aldehydes or acetals, access to protected amines is allowed.6 N-Alkylacetamides are formed when RCHO and MeCN are heated (microwave) with t-BuSiHMe2 and CF3CH2OH.7

N

Ph Ph P Cl Ir CO

NMe I O

N

Rh I O

N H

NMe

(1)

R

(2) Et3SiH

R'

MeO

+ (Me3Si)2NH

OMe

R

FeSO4 · 7H2O

R' NHCOOBn

CH2Cl2 25o

Reduction of secondary amides by Ru-catalysis to provide simple secondary amines or tertiary amines is dependent on the hydrosilane used.8 H Si

Si H O

OC

RCH2NHR'

CO Ru

CO

RCONHR'

Ru CO

H

Ru OC

CO

O

Si Me3SiO

SiMe3 O

n

R NR' R

A highly unusual reduction whereby methyl esters are converted to methyl ethers by Et3SiH at room temperature, is catalyzed by BF2OTf . OEt2 which is generated in situ from BF3 . OEt2 and Me3SiOTf.9 But perhaps because of the high reactivity of the catalyst toward other functional groups, the method is limited to use on relatively simple esters. Reductive cleavage of 2-tosyl-2-aza-7-oxabicyclo[2.2.1]heptan-5-ones by Et3SiH leads to either piperidine derivatives or tetrahydrofuran-3-ones, depending on the Lewis acid catalyst. Cleavage of the C(1)ZO bond is favored by the presence of TiCl4, whereas C(1)ZN bond cleavage facilitated by SnCl4 or BF3 . OEt2.10

Hydroxylamine diphenylphosphinate

247

Hydrosilylation. The PtO2-catalyzed reaction of diarylethynes with Me2Si(OEt)H, followed by treatment with Bu4NF, leads to (Z )-stilbenes in .95% stereoselectivity.11 Cycloaddition is observed when conjugated diynes and R2SiH2 are treated with [Cp Ru(MeCN)3]PF6 at room temperature.12 Aldol reaction.13 Trichlorosiloxyalkenes are generated in a debrominative silylation process from a-bromo ketones. Condensation with ArCHO leads to b-aryl enones. In the presence of the Lewis base Ph3PO the reaction is optimized. Ether synthesis.14 Carbonyl compounds undergo reductive etheriﬁcation with ROH in a reaction with Et3SiH, which is catalyzed by FeCl3. Addition.15 Markovnikov hydrocyanation of alkenes is accomplished employing TsCN and PhSiH3 and a (salen)Co complex in ethanol at room temperature. CN PhSiH3/EtOH

+ Ts-CN N O

Co

N O

1

Donohoe, T.J., Williams, O., Churchill, G.H. ACIE 47, 2869 (2008). Berthod, M., Favre-Reguillon, A., Mohamad, J., Mignani, G., Docherty, G., Lemaire, M. SL 1545 (2007). 3 Chen, T., Liu, X.-G., Shi, M. T 63, 4874 (2007). 4 Nishiyama, H., Furuta, A. CC 760 (2007). 5 Lai, R.-Y., Lee, C.-I., Liu, S.-T. T 64, 1213 (2008). 6 Yang, B.-L., Tian, S.-K. EJOC 4646 (2007). 7 Lehmann, F., Scobie, M. S 1679 (2008). 8 Hanada, S., Ishida, T., Motoyama, Y., Nagashima, H. JOC 72, 7551 (2007). 9 Morra, N.A., Pagenkopf, B.L. S 511 (2008). 10 Muthusamy, S., Krishnamurthi, J., Suresh, E. OL 8, 5101 (2006). 11 Giraud, A., Provot, O., Hamze, A., Brion, J.-D., Alami, M. TL 49, 1107 (2008). 12 Matsuda, T., Kadowaki, S., Murakami, M. CC 2627 (2007). 13 Smith, J.M., Greaney, M.F. TL 48, 8687 (2007). 14 Iwanami, K., Yano, K., Oriyama, T. CL 36, 38 (2007). 15 Gaspar, B., Carreira, E.M. ACIE 46, 4519 (2007). 2

Hydroxylamine diphenylphosphinate. Aziridination.1 Under basic conditions the title reagent delivers an NH group to conjugated ketones. 1

Armstrong, A., Baxter, C.A., Lamont, S.G., Pape, A.R., Wincewicz, R. OL 9, 351 (2007).

248

(2-Hydroxy-5-methoxyphenyl)diphenylmethanol

(2-Hydroxy-5-methoxyphenyl)diphenylmethanol. Acetalization.1 The title reagent condenses with carbonyl compounds to form 1,3dioxanes which are photolabile, therefore such derivatives are of special synthetic value. 1

Wang, P., Hu, H., Wang, Y. OL 9, 1533 (2007).

Hydroxy(tosyloxy)iodobenzene. Cyclization. The bridging of piperazine derivative at an a-position of a nitrogen atom to an indole nucleus requires dual activation of two types of CZH bonds. Achieving the transformation with PhI(OH)OTs [Koser reagent] in one step, albeit in low yields, is quite gratifying.1

N

AcN O

N NAc

O

Ph-I(OH)OTs

NAc

MeCN 85°

N

AcN N

O

O 35%

Ring contraction. Illustrated by the transformation of 1-aryl-1,2-dihydronaphthalenes to indanes2 the Koser reagent has the same ability as Tl(NO3)3 but of course its use avoids the issue of toxicity.

CH(OMe)2 Ph-I(OH)OTs MeOH 25o

Ar

Ar

1

Walker, S.J., Hart, D.J. TL 48, 6214 (2007). Silva, L.F. Jr, Siqueira, F.A., Pedrozo, E.C., Vieira, F.Y.M., Doriguetto, A.C. OL 9, 1433 (2007).

2

Hypoﬂuorous acid – acetonitrile. Oxidation. The exposure of a-amino esters to HOF-MeCN results in the formation of the corresponding a-nitroalkanoic esters.1 Rapid conversion of thiols and disulﬁdes to sulﬁnic acids or sulfonic acids in .90% yields occurs under similar conditions.2

Hypoﬂuorous acid – acetonitrile

249

Aldehydes are transformed into the corresponding nitriles via treatment of their N,N-dimethylhydrazones with HOF-MeCN.3 1

Harel, T., Rozen, S. JOC 72, 6500 (2007). Shefer, N., Carmeli, M., Rozen, S. TL 48, 8178 (2007). 3 Carmeli, M., Shefer, N., Rozen, S. TL 47, 8969 (2006). 2

I Imidazole-1-sulfonyl azide hydrochloride. Diazo group transfer.1 The title reagent, prepared by adding imidazole to NaN3 and SO2Cl2 in MeCN, is shelf-stable. It is useful in transfer a diazo group to amine and active methylene compounds. 1

Goddard-Borger, E.D., Stick, R.V. OL 9, 3797 (2007).

Indium. Tosylation. Alcohols and amines are tosylated by TsCl.1 However, the role played by indium metal in the protocol is questionable. Substitution. Indium-mediated reaction of iodoalkynes with glycals2 or glycosyl acetates3 gives C-glycosides.

RO

R'

O +

R' In(0)

RO OR

I

RO

CH2Cl2 Δ

O

RO OR

Indoles. Indium combined with hydriodic acid under phase transfer conditions has been used to convert 2-alkynylnitroarenes into indoles.4 Barbier reaction. Indium is activated by AgI or CuI/I2 to promote reaction of unactivated alkyl halides with aldehydes in water.5 Formation of allylindium species for reaction with sulﬁnimines in water is beneﬁted by a halide salt (of Na, Li, K, NH4), with regard to producing good yields of the adducts and diastereoselectivity.6 Of special interest is the reaction of the amphoteric 2-formylaziridines, which exist in dimeric form and expose one diastereoface to allylindium reagents. Accordingly, no protective group (on the nitrogen atom) is necessary prior to the reaction.7

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 251

252

Indium

R 2

R

NH

NH CHO

O

OH

Br

N

R

Ph

NH OH

In THF–H2O

R

Ph 90%

Addition and substitution. Addition of allylindium reagents to allenyl carbinols affords linear products.8 A net 1,3-butadien-2-ylation at the b-carbon of b-acetoxy-b-lactams results when they are treated with indium and 1,4-dibromo-2-butyne.9 OH

OH

R' In

R

R'

R

OH

OH

Br

C

R"

R"

Br R

OAc

R

In

+

DMF

NH

NH O

O

Br

A tertiary propargylic hydroxy group is subject to replacement (with transposition) on reaction with allylindium reagents, forming allenes.10 R' R'

+

Br R

R"

In

OH

THF

C

R"

R

A branched enyne unit is constituted from propargyl bromide to join up to RCHO in the presence of In –InBr3.11

RCHO

+

Br

OH

In–InBr3

R

A method for N-alkylation of a-amino esters by RCHO and R0 I employing In/Ag and InCl3 in aqueous MeOH has been developed.12 It involves formation of organoindium reagents and imines, and their mutual reaction.

Indium(III) acetate – phenylsilane

253

A p-allylpalladium moiety is changed to the nucleophilic p-allylindium counterpart by interaction with In –InCl3.13 For an ensuing coupling reaction roles played by two partner reactants are reversed.

X In–InCl3

Y

OAc n

(Ph3P)4Pd LiCl, BuNMe2

Y

n

Allylindium species are cleaved to C-centered radicals therefore they are alternatives to allyltins for ring closure. UV irradiation is beneﬁcial to the chemical step.14 Cleavage of 2,2,2-trichloroethyl esters.15 Carboxylic acids are liberated by treatment with indium from trichloroethyl esters via chlorine atom abstraction, reduction and fragmentation. However, those esters of arylacetic acids and 3-arylpropanoic acids behave differently, due to the tendency for the dichloromethyl radical to abstract a benzylic hydrogen. 1

Kim, J.-G., Jang, D.O. SL 2501 (2007). Lubin-Germain, N., Hallonet, A., Huguenot, F., Palmier, S., Uziel, J., Auge, J. OL 9, 3679 (2007). 3 Lubin-Germain, N., Baltaze, J.-P., Coste, A., Hallonet, A., Laureano, H., Legrave, G., Uziel, J., Auge, J. OL 10, 725 (2008). 4 Kim, J.S., Han, J.H., Lee, J.J., Jun, Y.M., Lee, B.M., Kim, B.H. TL 49, 3733 (2008). 5 Shen, Z.-L., Yeo, Y.-L., Loh, T.-P. JOC 73, 3922 (2008). 6 Sun, X.-W., Liu, M., Xu, M.-H., Lin, G.-Q. OL 10, 1259 (2008). 7 Hili, R., Yudin, A.K. ACIE 47, 4188 (2008). 8 Kim, S., Lee, P.H. EJOC 2262 (2008). 9 Lee, K., Lee, P.H. CEJ 14, 8877 (2007). 10 Lee, K., Lee, P.H. OL 10, 2441 (2008). 11 Huang, J.-M., Luo, H.-C., Chen, Z.-X., Yang, G.-C. EJOC 295 (2008). 12 Shen, Z.-L., Cheong, H.-L., Loh, T.-P. CEJ 14, 1875 (2008). 13 Seomoon, D., Lee, K., Kim, H., Lee, P.H. CEJ 13, 5197 (2007). 14 Hirashita, T., Hayashi, A., Tsuji, M., Tanaka, J., Araki, S. T 64, 2642 (2008). 15 Mineno, T., Kansui, H., Kunieda, T. TL 48, 5027 (2007). 2

Indium(III) acetate – phenylsilane. Reduction. In EtOH catalytic amounts of In(OAc)3 and 2,6-lutidine in dry air initiate the reduction of RX (X ¼ Br, I) to hydrocarbon products by PhSiH3.1 Radical addition. Under essentially identical conditions as above, alkyl iodides generate free radicals which are trapped by alkenes (e.g., acrylic esters).2 1

Miura, K., Tomita, M., Yamada, Y., Hosomi, A. JOC 72, 787 (2007). Miura, K., Tomita, M., Ichikawa, J., Hosomi, A. OL 10, 133 (2008).

2

254

Indium(III) bromide

Indium(III) bromide. 3,4-Dibromotetrahydropyrans.1 Prins cyclization involving RCHO and homoallylic alcohols bearing a bromine atom at the far end of the double bond, as induced by InBr3 and terminated by Me3SiBr, is stereoselective. R'

OH +

R

InBr3

R'CHO

Br

O

Me3SiBr

Br

R

Br R'

OH Br

R

+

R'CHO

InBr3

O

Me3SiBr

R

Br Br

Carbocyclization. Opening of an epoxide induced by InBr3 can lead to polycarbocyclic products due to participation of double bond(s) and aromatic ring.2

InBr3 CH2Cl2 25o

O

HO 57%

Friedel –Crafts alkenylation involving the triple bond of an o-isothiocyanatoarylalkyne and initiated by InBr3 [or In(OTf)3] leads to a 4-substituted quinoline-2-thione.3 Best results are obtained from alkynes with a t-butyl group at the other end of the triple bond (which is lost during the reaction).

Ar + N

C

S

ArH

SAr

InX3 150o

N H

S

ArH = anisole

N H

S

ArH = PhSH, PhSMe

Alkylation 1 allylation.4 A carbon chain is constructed from an enol silyl ether (including ketene silyl acetal, . . .) with an alkylating agent and an allylsilane with catalysis of InBr3 in CH2Cl2 at room temperature.

Indium(III) chloride

Ar

Cl

+

OSiMe3

+

SiMe3

255

OH

InBr3

Ar

CH2Cl2 25o

Addition reactions. With InBr3 as catalyst sulfonamides are induced to add to unactivated alkenes in reﬂuxing toluene.5 Carbamates and arylamines do not react in the same way. A formal hydroamination is the ring closure of N-tosyl-o-alkynylaryl amines to furnish indoles. Cyclization with sulfonyl group migration to the aryl nucleus is limited to substrates that contain an o-methoxy substituent to the nitrogen atom. It should be noted that similar but simpler N-mesylarylamines (without the methoxy group) undergo cyclization to form 3-sulfonylindoles when AuBr3 instead of InBr3 is used as catalyst.6

R' InBr3

N OMe Ts

R

PhMe 80o

R'

R' Ts

N OMe R

Ms InBr3

R N Ms

PhMe 80o

R' N R

In an addition of 3-methyl-1-butyn-3-ol to aldehydes in the presence of (S)-BINOLInBr3 and an amine, acceleration by ligand is signiﬁcant.7 1

Liu, F., Loh, T.-P. OL 9, 2063 (2007). Zhao, J.-F., Zhao, Y.-J., Loh, T.-P. CC 1353 (2008). 3 Otani, T., Kunimatsu, S., Nihei, H., Abe, Y., Saito, T. OL 9, 5513 (2007). 4 Nishimoto, Y., Yasuda, M., Baba, A. OL 9, 4931 (2007). 5 Huang, J.-M., Wong, C.-M., Xu, F.-X., Loh, T.-P. TL 48, 3375 (2007). 6 Nakamura, I., Yamagishi, U., Song, D., Konta, S., Yamamoto, Y. ACIE 46, 2284 (2007). 7 Harada, S., Takita, R., Ohshima, T., Matsunaga, S., Shibasaki, M. CC 948 (2007). 2

Indium(III) chloride. Friedel– Crafts acylation. Carboxylic acids are converted into RCOCl with Me2Si(H)Cl and InCl3.1 In the presence of an activated arene (e.g., an aryl ether) an aryl ketone is formed.1 A dual role is played by InCl3.

256

Indium(III) chloride

RCOOH

InCl3

H

+

InCl3

RCOCl

RCOAr

ArH

Si Cl

Addition to CvO. Triethoxysilane and allyltriethoxysilane react with ArCHO to give benzyl ethyl ethers. The reaction is accomplished with a mixture of InCl3 and Me3SiCl.2 2,3-Dimethyl-1,3-butadiene is converted into an allylating agent by a mixture of InCl3 and Bu3SnH, which forms HInCl2 in situ. The regioselectivity for reaction with ketones is temperature dependent, g-adducts are formed at room temperature, a-adducts in reﬂuxing THF.3 Glucal undergoes isomerization and dehydration to give 2-furylethanediol by treatment with InCl3 in an ionic liquid.4 Substitution reactions. Secondary alcohols are homologated to furnish N-tosylmethylcarboxamides on treatment with TsCH2NC in the presence of InCl3.5 O OH

R

InCl3

+

CN

Ts

R

MeCN

R'

R'

N H

Ts

Desilylalkylation of allylsilanes by a trimethylsilyl ether involves formation of an activating complex [Me3SiI/InCl3] for ROSiMe3. Iodine is needed in addition to InCl3 in this reaction.6 R R"-OSiMe3

SiMe3

+

I2 –InCl3

R

R'

R'

R"

Homoallylic amine derivatives are obtained from reaction of a-aminoalkyl p-tolyl sulfones and allylsilanes.7 The intermolecular Friedel –Crafts alkylation with benzylic and allylic halides occurs at room temperature in CH2Cl2.8 Diarylmethanes are also obtained in moderate yields from arenes and benzyl alcohols on heating the mixtures with InCl3 . 4H2O and acetylacetone at 1208.9 1-Vinyltetralin and 4-vinyltetrahydroisoquinoline derivatives are readily formed by an intramolecular allylation.10 R

R InCl3

Z

CH2Cl2

Br Z = NTs, C(COOEt)2

Z

Indium(I) iodide

257

Reaction of 1,3-diones with propargylic alcohols leads to 3-acylfurans.11 Using other Lewis acids such as FeCl3 the reaction stops short of cyclization. Alkylation by alkenes (styrene, norbornene, cyclopentadiene, dihydropyran, . . .) affords moderate yields of the adducts.12 Again, InCl3 appears to show a special catalytic activity, as AlCl3, TiCl4, MnCl2, BiCl3 are ineffective. O

O O

+

InCl3

O

PhCl 110o

OH

Ph

Ph

R

R

For the Pd(0)-catalyzed cross-coupling of heteroarylmetals with ArI the use of indium derivatives (prepared from the corresponding lithio compounds) is a success.13 1

Babu, S.A., Yasuda, M., Baba, A. OL 9, 405 (2007). Yang, M.-S., Xu, L.-W., Qiu, H.-Y., Lai, G.-Q., Jiang, J.-X. TL 49, 253 (2008). 3 Hayashi, N., Honda, H., Shibata, I., Yasuda, M., Baba, A. SL 1407 (2008). 4 Teijeira, M., Fall, Y., Santamarta, F., Tojo, E. TL 48, 7926 (2007). 5 Krishna, P.R., Sekhar, E.R., Prapurna, Y.L. TL 48, 9048 (2007). 6 Saito, T., Nishimoto, Y., Yasuda, M., Baba, A. JOC 72, 8588 (2007). 7 Das, B., Damodar, K., Saritha, D., Chowdhury, N., Krishnaiah, M. TL 48, 7930 (2007). 8 Kaneko, M., Hayashi, R., Cook, G.R. TL 48, 7085 (2007). 9 Sun, H.-B., Li, B., Chen, S., Li, J., Hua, R. T 63, 10185 (2007). 10 Hayashi, R., Cook, G.R. OL 9, 1311 (2007). 11 Feng, X., Tan, Z., Chen, D., Shen, Y., Guo, C.-C., Xiang, J., Zhu, C. TL 49, 4110 (2008). 12 Yuan, Y., Shi, Z. SL 3219 (2007). 13 Font-Sanchis, E., Cespedes-Guirao, F.J., Sastre-Santos, A., Fernandez-Lazaro, F. JOC 72, 3589 (2007). 2

Indium(III) chloride – aluminum. Reduction. Both anthraquinones and anthrones are reduced to anthracenes by aluminum at room temperature, with InCl3 present in catalytic amounts.1 Pinacol coupling. In aqueous media the coupling of ArCOR is achieved by Al– InCl3.2 1

Wang, C., Wan, J., Zheng, Z., Pan, Y. T 63, 5071 (2007). Wang, C., Pan, Y., Wu, A. T 63, 429 (2007).

2

Indium(I) iodide. Allylation. Allyl(pinacolato)boron and analogues transfer the allyl group to ketones1 in the presence of InI. The reaction is highly chemoselective therefore many functional groups are tolerated.

258

Indium(III) triﬂate

The reaction with N-acylhydrazones is characterized by high regioselectivity and diastereoselectivity.2

NNHBz R

NHNHBz +

R'

O B O

InI

R R'

i-PrOH

1

Schneider, U., Kobayashi, S. ACIE 46, 5909 (2007). Kobayashi, S., Konishi, H., Schneider, U. CC 2313 (2008).

2

Indium(III) triﬂate. Acetalization. As catalyst for acetalization of carbonyl compounds that are acidsensitive, In(OTf)3 offers another choice.1,2

b-Amino alcohols. meso-Epoxides undergo aminolysis in the presence of In(OTf)3. The reaction is rendered enantioselective by adding the bipyridyl ligand 1.3

N OH

N HO

(1) a-Methylene-g-lactones. The regioselectivity for allylation of aldehydes with a-(pinacolatoboryl)methyl-a,b-unsaturated esters is dependent on the acidity of the catalyst.4

In(OTf)3

R

+ R'CHO

CHR

R' O

COOMe

O B O O

R Yb(OTf)3

R' O O

Alkenylation and allylation. 1,3-Dicarbonyl compounds are alkenylated by alkynes under solvent-free conditions.5

Indium(III) triﬂate

259

C6H13 COOEt

InX3

+ COOEt

60o

C6H13

O

O

50%

Mixtures of epoxides and 3-substituted 2-methyl-4-penten-2-ols react to give homoallylic alcohols, on treatment with In(OTf)3 (or TfOH). Under the reaction conditions the tertiary alcohols are decomposed to generate allylating agents while the epoxides undergo rearrangement to aldehydes, the transformed species then combine to furnish the observed products.6

R

O

R

OH

+

R'

R' In(OTf)3

R R

R"

R" OH

Retro-Claisen reaction. Cleavage of 1,3-diketones by an alcohol (e.g., phenethyl alcohol) takes place when they are heated with In(OTf)3.7 O

O +

Ph

HO

In(OTf)3

Ph

O

O

O

95%

Cycloisomerization. Allenyl carbonyl compounds bearing a phenyl group at the g-position are susceptible to cyclization to give products with a furan ring. Phenyl migration is involved.8 Ph

Ph In(OTf)3

C R

R' O

1

PhMe 100o

R

O

R'

Smith, B.M., Graham, A.E. TL 47, 9317 (2006). Gregg, B.T., Golden, K.C., Quinn, J.F. T 64, 3287 (2008). 3 Mai, E., Schneider, C. SL 2136 (2007). 4 Ramachandran, P.V., Pratihar, D. OL 9, 2087 (2007). 5 Endo, K., Hatakeyama, T., Nakamura, M., Nakamura, E. JACS 129, 5264 (2007). 6 Nokami, J., Maruoka, K., Soua, T., Tanaka, N. T 63, 9016 (2007). 7 Kawata, A., Takata, K., Kuninobu, Y., Takai, K. ACIE 46, 7793 (2007). 8 Dudnik, A.S., Gevorgyan, V. ACIE 46, 5195 (2007). 2

260

Indium(III) triﬂimide

Indium(III) triﬂimide. Cyclization.1 Intramolecular alkenylation of b-keto esters is carried out with In(NTf2)3 in toluene at 1008, good yields of cyclic ketones (6- to 15-membered) are generally obtained.

O OH

COOEt

COOEt

In(NTf2)3 PhMe 100o

1

Tsuji, H., Yamagata, K., Itoh, Y., Endo, K., Nakamura, M., Nakamura, E. ACIE 46, 8060 (2007).

Iodine. Iodination. Arenes including some electron-poor members such as haloarenes, triﬂuoromethylbenzene, and benzoic acid, are iodinated by I2 in an acidic medium (H2SO4HOAc or CF3COOH-CH2Cl2) with K2S2O8 present.1 It is also possible to activate iodine to iodinate electron-rich arenes by CAN,2 and by NaNO2 with air as oxidant to fully utilize I2.3 a-Iodination of alkyl aryl ketones is accomplished with I2 –CuO in reﬂuxing MeOH.4 N-Substituted 2,3-diiodoindoles are obtained when the 2-indolecarboxylic acids are treated with iodine and NaHCO3.5 There is a review on electrophilic iodination with elemental iodine and other systems.6 Substitutions. Iodine assists the SN2 substitution of allylic alcohols to form sulfonamides and carbamates.7 Allylic alcohols are sufﬁciently electrophilic toward 1,3-dicarbonyl compounds in the presence of iodine.8 Peroxidation. Ketones are transformed into gem-bisperoxyalkanes using ROOH and iodine.9 Bishydroperoxides are similarly prepared using H2O2.10

R

I2

O R'

+ R"OOH

MeCN

R

OOR"

R'

OOR"

Friedel– Crafts reaction. Iodine is a mild catalyst for the Pictet-Spengler reaction of tryptamine with ketones to generate tetrahydro-b-carbolines at room temperature.11

Iodosuccinimide, NIS

261

Cyclotrimerization of pyrrole-fused 1,3-dioxepanes occurs in the presence of iodine.12

COOEt O

MeO

O

NH OMe

I2 MeOH

N H

HN

COOEt

COOEt

N H

EtOOC OMe

1

Hossein, M.D., Oyamada, J., Kitamura, T. S 690 (2008). Das, B., Krishnaiah, M., Venkateswarlu, K., Reddy, V.S. TL 48, 81 (2007). 3 Iskra, J., Stavber, S., Zupan, M. TL 49, 893 (2008). 4 Yin, G., Gao, M., She, N., Hu, S., Wu, A., Pan, Y. S 3113 (2007). 5 Putey, A., Popowycz, F., Joseph, B. SL 419 (2007). 6 Stavber, S., Jereb, M., Zupan, M. S 1487 (2008). 7 Wu, W., Rao, W., Er, Y.Q., Loh, J.K., Poh, C.Y., Chen, P.W.H. TL 49, 2620 (2008). 8 Rao, W., Tay, A.H.L., Goh, P.J., Choy, J.M.L., Ke, J.K., Chen, P.W.H. TL 49, 122 (2008). 9 Zmitek, K., Zupan, M., Stavber, S., Iskra, J. JOC 72, 6534 (2007). 10 Selvam, J.J.P., Suresh, V., Rajesh, K., Babu, D.C., Suryakiran, N., Venkateswarlu, Y. TL 49, 3463 (2008). 11 Lingam, Y., Rao, D.M., Bhowmik, D.R., Santu, P.S., Rao, K.R., Islam, A. TL 48, 7243 (2007). 12 Stepieri, M., Sessler, J.L. OL 9, 4785 (2007). 2

Iodosuccinimide, NIS. Iodination. Practical and highly stereoselective iododesilylation of alkenylsilanes is performed with NIS in hexaﬂuoroisopropanol.1 Treatment of 2-alkynyl-2-trimethylsiloxy carbonyl compounds with NIS leads to 4-iodo3-furanones.2 In some cases the presence of AuCl3 (5 mol%) is beneﬁcial. R" O

R"

O

NIS

R Me3SiO

R'

CH2Cl2 23

o

I

R R'

O

Interesting difference in iodocyclization that is participated by NIS and I2 is noted, for which slight variation of the substrate structure is rather difﬁcult to account.3

262

Iodosylbenzene

I OH

NIS CH2Cl2

N

N Ph

Ph

Ph

O Ph

94% O OH

I2 – K2CO3 MeCN (H2O)

N Ph

N

Ph

80%

De-N-methylation. The N-methyl group of N-benzyl-N-methyl a-amino acid derivatives is selectively removed by treatment with NIS, then MeONH3Cl in MeCN at room temperature.4 1

Ilardi, E.A., Stivala, C.E., Zakarian, A. OL 10, 1727 (2008). Crone, B., Kirsch, S.F. JOC 72, 5435 (2007). 3 Halim, R., Scammells, P.J., Flynn, B.L. OL 10, 1967 (2008). 4 Katoh, T., Watanabe, T., Nishitani, M., Ozeki, M., Kajimoto, T., Node, M. TL 49, 598 (2008). 2

Iodosylbenzene. Epoxidation. Epoxidation of alkenes by PhIO is co-catalyzed by a Mn-porphyrin and nanosized gold stabilized by RSH.1 Nitrenoids. In situ oxidation of Cl3CCH2OSO2NH2 by PhIO gives the nitrene that can be delivered to alkenes to form aziridines by azolecarbene-coordinated copper species.2 Cleavage of CvC bond. Adduct of PhIvO with tetraﬂuoroboric acid serves as ozone equivalent in its capacity of cleaving alkenes to dialdehyde in the presence of 18-crown-6.3 1

Murakami, Y., Konishi, K. JACS 129, 14401 (2007). Xu, Q., Appella, D.H. OL 10, 1497 (2008). 3 Miyamoto, K., Tada, N., Ochiai, M. JACS 129, 2772 (2007). 2

o-Iodoxybenzoic acid, IBX. Degradation. Carboxamides lose a one-carbon unit to give nitriles on heating with IBX and Et4NBr.1 The reaction involves generation of Brþ to induce a Hofmann rearrangement. Glycinamides give cyanamides.2

R2N

CONH2

MeCN 60o O

OH I O O

R2N—CN

o-Iodoxybenzoic acid, IBX

263

Oxidation. Secondary a-amino nitriles afford a-imino nitriles upon reactin with IBX at room temperature.3 Tetrahydroisoquinoline is carbamoylated at C-1 and N-acylated at the same time on exposure to IBX and treatment with RCOOH and R0 NC.4

IBX

NH

RCOOH

N

THF

N

COR CONHR'

R'NC

The method for conversion of benzylic bromide to aldehyde with IBX and DMSO has been applied to a molecule containing six such structural units, to deliver a precursor of the belt-shaped [6.8]3cyclacene by a threefold intramolecular McMurry coupling.5 o-Quinones. o-Oxygenation of a phenol to give a catechol intermediate constitutes a critical step in a synthesis of brazilin. Oxidation with IBX to give an o-quinone followed by reduction (with Na2S2O4) accomplishes this transformation.6 HO

HO

O OBn

O O

IBX;

HO

OH

OBn

Na2S2O4

HO

HO

OH

HO

OH brazilin

Substituted IBX analogues. Tetraﬂuoro-IBX (1) has been synthesized from 2,3,4,5tetraﬂuorobenzoic acid. It is more soluble in organic solvents and shows higher reactivity comparing to the parent IBX.7 Compound 2 is another analogue.8 F F

O

OH

O

I O

F F

(1) 1

O

OH

I O

MeO O

(2)

Bhalerao, D.S., Mahajan, U.S., Chaudhari, K.H., Akamanchi, K.G. JOC 72, 662 (2007). Chaudhari, K.H., Mahajan, U.S., Bhalerao, D.S., Akamanchi, K.G. SL 2815 (2007). 3 Fontaine, P., Chiaroni, A., Masson, G., Zhu, J. OL 10, 1509 (2008). 4 Ngouansavanh, T., Zhu, J. ACIE 46, 5775 (2007). 5 Esser, B., Rominger, F., Gleiter, R. JACS 130, 6716 (2008). 6 Huang, Y., Zhang, J., Pettus, T.R.R. OL 7, 5841 (2005). 7 Richardson, R.D., Zayed, J.M., Altermann, S., Smith, D., Wirth, T. ACIE 46, 6529 (2007). 8 Moorthy, J.N., Singhal, N., Senapati, K. TL 49, 80 (2008). 2

264

Ionic liquids

Ionic liquids. Special ionic liquids. A review of chiral ionic liquids is available.1 A series of Lewis basic ionic liquids are prepared from DABCO by quaternization with RCl followed by anion exchange (to BF4, PF6).2 Some more signiﬁcant applications. Aldol reaction in ionic liquids is catalyzed by O-silylserines.3 Michael reaction between malonitrile and chalcones proceeds without the usual catalysts using ionic liquids as reaction media, presumably the acidity of the carbon acid is enhanced.4 CAN oxidation in ionic liquids5 is a useful development in view of the limitation in solvent systems for such a reagent. Depolymerization of nylon-6 to give caprolactam occurs when it is heated with DMAP in an ionic liquid at 3008.6 Phosphonium ionic liquids are good media for Pd-catalyzed carbonylation7 and the Buchwald-Hartwig amination.8 However, they must contain noncoordinating counteranions such as bistriﬂamide. A synthesis of a-substituted acrylamides from 1-alkynes, amines and carbon monoxide based on catalysis by Pd(OAc)2 –DPPP is carried out in (bmim)NTf2.9 While most synthetic applications have involved imidazolium ionic liquids, N-butylpyridinium salts are used in Sonogashira coupling.10 Ionic liquids are proposed as “designer solvents” for nucleophilic aromatic substitution.11 Coating with a layer of ionic liquid onto silica-supported sulfonic acid improves its utility (such as acetalization) boasting selectivity in aqueous media.12 1

Winkel, A., Reddy, P.V.G., Wilhelm, R. S 999 (2008). Wykes, A., MacNeil, S.L. SL 107 (2007). 3 Teo, Y.-C., Chua, G.-L. TL 49, 4235 (2008). 4 Meciarova, M., Toma, S. CEJ 13, 1268 (2007). 5 Mehdi, H., Bodor, A., Lantos, D., Horvath, I.T., De Vos, D.E., Binnemans, K. JOC 72, 517 (2007). 6 Kamimura, A., Yamamoto, S. OL 9, 2533 (2007). 7 McNulty, J., Nair, J.J., Robertson, A. OL 9, 4575 (2007). 8 McNulty, J., Cheekoori, S., Bender, T.P., Coggan, J.A. EJOC 1423 (2007). 9 Li, Y., Alper, H., Yu, Z. OL 8, 5199 (2006). 10 de Lima, P.G., Antunes, O.A.C. TL 49, 2506 (2008). 11 Newington, I., Perez-Arlandis, J.M., Welton, T. OL 9, 5247 (2007). 12 Gu, Y., Karam, A., Jerome, F., Barrault, J. OL 9, 3145 (2007). 2

Iridium complexes. Addition reactions. Spiroacetal formation from dihydroxyalkynes1 is the result of a triple bond activation by iridium complex (1). Prenylation of an aldehyde from its mixture with 1,1-dimethylallene under hydrogen is signiﬁcant as the nucleophilic species is highly substituted.2 Alcohols are dehydrogenated in the presence of proper iridium complexes (cf. 23 and 34) therefore the same type of products are accessible while obviating hydrogen gas.5

Iridium complexes

N

N

Ph4B

Ir CO Ph P CO Ph

(1)

HO

O O

OH

(1)

R"

R'

R

265

R' R"

[(cod)Ir(biphep)]BArF

+

C

OH

Cs2CO3,

R

i-PrOH

OH MeO OMe BIPHEP Ph2P PPh2

TfO H N

Ir

H N

N

Cl

Ir Cl OH

(2)

(3)

An analogous complex of 1 (with a 3,5-diisopropylpyrazolylethyl group in the phosphine ligand and COD in place of two CO groups) is found to catalyze intramolecular hydroamination of properly constituted alkynes to afford cyclic imines.6 Alkenylation of activated ketones (e.g., a-keto esters7) and N-tosylimines8 is similarly performed by the in situ reductive activation of alkynes (under H2).

Hydrodehalogenation. Alkyl halides are reduced by Ir-catalyzed reaction with Et3SiH.9

O O Ir Ph P P Ph Ph H O Ph

(4)

(C6F5)4B

(4)

R–X + Et3SiH X = F, Cl, Br, I

R—H

266

Iron(II) acetate

Nazarov cyclization. 2-Siloxy-4-alkenoylfurans fail to undergo Nazarov cyclization in the presence of conventional Lewis acids, but the reaction can be brought forth with addition of an iridium complex.10 However, whether the true catalyst is a highly electrophilic silicon species cannot be excluded. O Ph OC

I

Me

Ph

TIPSO

P

O

Ir P

I

Ph

(5)

F3C

Ph

2

CH2Cl2

OTIPS

B 2 F3C

(5)

O O 67%

1

Messerle, B.A., Vuong, K.Q. OM 26, 3031 (2007). Skucas, E., Bower, J.F., Krische, M.J. JACS 129, 12678 (2007). 3 Ko¨nigsmann, M., Donati, N., Stein, D., Scho¨nberg, H, Harmer, J., Sreekanth, A., Gru´´tzmacher, H. ACIE 46, 3567 (2007). 4 Fujita, K., Tanino, N., Yamaguchi, R. OL 9, 109 (2007). 5 Bower, J.F., Skucas, E., Patman, R.L., Krische, M.J. JACS 129, 15134 (2007). 6 Field, L.D., Messerle, B.A., Vuong, K.Q., Turner, P., Failes, T. OM 26, 2058 (2007). 7 Ngai, M.-Y., Barchuk, A., Krische, M.J. JACS 129, 280 (2007). 8 Barchuk, A., Ngai, M.-Y., Krische, M.J. JACS 129, 8432 (2007). 9 Yang, J., Brookhart, M. JACS 129, 12656 (2007). 10 He, W., Huang, J., Sun, X., Frontier, A.J. JACS 130, 300 (2008). 2

Iron(II) acetate. Hydrosilylation.1 A protocol for reductive silylation of ketones by (EtO)2SiMeH includes addition of Fe(OAc)2 and sodium 2-thienylcarboxylate. 1

Furuta, A., Nishiyama, H. TL 49, 110 (2008).

Iron(II) bromide. 2,6-Diacetylpyridine bis-N-(2,6-diisopropylphenyl)imine complex. The readily synthesized air-stable complex is reduced in situ by NaBEt3H to catalyze intramolecular [2þ2]cycloaddition.1 Also the bromine atoms of the complex can be exchanged to dinitrogen so as to catalyze hydrogenation of aryl azides to give arylamines.2 1

Bouwkamp, M.W., Bowman, A.C., Lobkovsky, E., Chirik, P.J. JACS 128, 13340 (2006). Bart, S.C., Lobkovsky, E., Bill, E., Chirik, P.J. JACS 128, 5302 (2006).

2

Iron(III) chloride

267

Iron(II) chloride. Redox reactions. When complexed to a porphyrin ligand FeCl2 mediates the reduction of a-alkoxy ketones with i-PrOH –NaOH.1 An activation system for the CZH bond constituted from FeCl2 and (t-BuO)2 enables the union of indan, tetralin and diphenylmethane with b-diketones.2 Activation of cycloalkanes is more remarkable.3 O

O

COOR

COOR FeCl 2 O O

+

100o

1

Enthaler, S., Spilker, B., Erre, G., Junge, K., Tse, M.K., Beller, M. T 64, 3867 (2008). Li, Z., Cao, L., Li, C.-J. ACIE 46, 6505 (2007). 3 Zhang, Y., Li, C.-J. EJOC 4654 (2007). 2

Iron(III) chloride. Deacetalization. Diols protected as 1,2,-butanediacetals are released on treatment with FeCl3 in HOAc at room temperature.1 Arylation. Traditionally, arylation of nucleophiles is carried out in the presence of copper catalysts, the use of FeCl3 as an alternative, with its scope has now been delineated. In the synthesis of diaryl ethers, 1,3-di-t-butyl-1,3-propanedione serves an additive (ligand for the Fe3þ ion) and Cs2CO3 as base.2 N,N 0 -Dimethylethylenediamine appears to be an excellent ligand in the reaction with N-nucleophiles (N-heterocycles,3 amides4) in a nonpolar solvent (toluene) where a milder base (K3PO4) sufﬁces, arylation of alkanethiols calls for t-BuONa.5 C-Arylation of 1-alkynes is similarly accomplished.6 FeCl 3 –DMEDA

R

+

ArI

Cs2CO3 / PhMe

R

Ar

135o

Friedel– Crafts reactions. Benzyl ethers are activated by FeCl3 to react with arenes to provide diarylmethanes.7 N-Tosylimines and aziridines also become electrophilic toward electron-rich arenes.8 Remarkably mild conditions are needed for the ring closure of N-aryl-N-hydroxypropargylamine derivatives to afford 4-allenylidene-1,2,3,4-tetrahydroisoquinolines.9

268

Iron(III) chloride

R

R

R' OH

R' C

FeCl3 · 6H2O MeNO2

NTs

NTs

25o

One of the difﬁcult tasks in completing a synthesis of dimeric Vinca alkaloids such as vinblastine is the joining of two monomeric portions. Friedel –Crafts alkylation must be carried out in relatively mild conditions to avoid destruction of the many sensitive functional groups. An elegant solution to the synthetic problem involves oxidation of catharanthine and trapping the reactive species with vindoline. The intermolecular CC bond formation also implies fragmentation of the bridged ring system of catharanthine, most importantly in a stereoselective manner and having the emerging stereocenter in the natural conﬁguration. Using FeCl3 (in 0.1 N HCl) as oxidant and CF3CH2OH as cosolvent, such a task can be achieved at room temperature.10

N

N FeCl 3

N H

H

0.1 N HCl CF3CH2OH

COOMe

cathranthine

OAc COOMe N H OH

N H MeOOC MeO

N

+

N

OAc COOMe

90%

N H OH

MeO

vindoline

Alone or complexed to MeNO2 or Ph2CO as Friedel –Crafts alkylation catalyst to functionalize polystyrene resin with N-chloromethylphthalimide to produce aminomethylated polymer (for solid phase peptide synthesis), FeCl3 performs well.11 Cyclization reactions. 3-Cyano-N-alkoxyindoles are formed when a-cyanobenzyl oxime ethers are oxidized with FeCl3 (a one-electron oxidant). Cyclization follows the generation of the benzylic radicals.12 CN R NOR'

FeCl 3 CH2Cl2

Ph

NFeCl 2 C R NOR'

CN R N OR'

Addition of carboxylic acids to alkenes (e.g., norbornene) is promoted by FeCl3 –AgOTf in reﬂuxing 1,2-dichloroethane. Unsaturated carboxylic acids give g-lactones.13

Iron(III) nitrate

269

Addition and cycloaddition. Styrenes are transformed into benzylamine derivatives by hydroamination with TsNH2.14 More unusual is the regioselective addition of arenes across the triple bond of an alkynylarene, as catalyzed by FeCl3.15 Ar' ArH

FeCl 3

+

MeNO2

R

Ar' CHR Ar

1-Oxallyl cations are readily generated from 2-alkenyl-1,3-dioxolanes. Bicyclo[n.2.0]cycloalkanes can be prepared by intramolecular trapping of such reactive intermediates.16 O

O

H FeCl 3 / SiO2

O

O H

Substitution. Secondary benzylic and allylic alcohols are converted to carboxamido and sulfonamido derivatives by amides and sulfonamides, respectively, in the presence of FeCl3.17 1

Tzschucke, CC., Pradidphoe, N., Dieguez-Vazquez, A., Kongkathip, B., Kongkathip, N., Ley, S.V. SL 1293 (2008). 2 Bistri, O., Correa, A., Bolm, C. ACIE 47, 586 (2008). 3 Correa, A., Bolm, C. ACIE 46, 8862 (2007). 4 Correa, A., Elmore, S., Bohm, C. CEJ 14, 3527 (2008). 5 Correa, A., Carril, M., Bolm, C. ACIE 47, 2880 (2008). 6 Carril, M., Correa, A., Bolm, C. ACIE 47, 4862 (2008). 7 Wang, B.-Q., Xiang, S.-K., Sun, Z.-P., Guan, B.-T., Hu, P., Zhao, K.-Q., Shi, Z.-J. TL 49, 4310 (2008). 8 Wang, Z., Sun, X., Wu, J. T 64, 5013 (2008). 9 Huang, W., Shen, Q., Wang, J., Zhou, X. JOC 73, 1586 (2008). 10 Ishikawa, H., Colby, D.A., Boger, D.L. JACS 130, 420 (2008). 11 Zikos, C., Alexiou, G., Ferderigos, N. TL 47, 8711 (2006). 12 Du, Y., Chang, J., Reiner, J., Zhao, K. JOC 73, 2007 (2008). 13 Komeyama, K., Mieno, Y., Yukawa, S., Morimoto, T., Takaki, K. CL 36, 752 (2007). 14 Michaux, J., Terrasson, V., Marque, S., Wehbe, J., Prim, D., Campagne, J.-M. EJOC 2601 (2007). 15 Li, R., Wang, S.R., Lu, W. OL 9, 2219 (2007). 16 Ko, C., Feltenberger, J.B., Ghosh, S.K., Hsung, R.P. OL 10, 1971 (2008). 17 Jana, U., Maiti, S., Biswas, S. TL 49, 858 (2008).

Iron(III) nitrate. Hydroxymethylation. Formaldehyde is incorporated into b-dicarbonyl compounds by catalysis of Fe(NO3)3 . 9H2O. The reaction performed in water at room temperature is facilitated by sodium p-dodecylbenzenesulfate.1

270

Iron(III) perchlorate

Oxidation. Heating an alcohol with Fe(NO3)3 . 9H2O at 80o leads to its conversion into the carbonyl compound. However, the scope of the oxidation is not well studied, and its applicability (to give good yields) may be limited to benzylic alcohols.2 1

Ogawa, C., Kobayashi, S. CL 36, 56 (2007). Namboodiri, V.V., Polshettiwar, V., Varma, R.J. TL 48, 8839 (2007).

2

Iron(III) perchlorate. Transalkoxylation. Facile exchange of the alkoxy group of an 2-alkoxytetrahydrofuran occurs on its treatment with ROH and Fe(ClO4)3 . 6H2O.1 1

Yamanaka, D., Matsunaga, S., Kawamura, Y., Hosokawa, T. TL 49, 53 (2008).

Iron(III) sulfate. Modiﬁcation of sugars. Acid-sensitive sugars can be peracetylated using Ac2O in the presence of Fe2(SO4)3 . xH2O.1 Ferrier rearrangement is accomplished by treatment with the Fe(III) salt.2 1

Shi, L., Zhang, G., Pan, F. T 64, 2572 (2008). Zhang, G., Liu, Q., Shi, L., Wang, J. T 64, 339 (2008).

2

Iron(III) tosylate. Allylation. The title salt is another catalyst for allyl transfer from allylsilanes to aldehydes and acetals.1 1

Spafford, M.J., Anderson, E.D., Lacey, J.R., Palma, A.C., Mohan, R.S. TL 48, 8665 (2007).

Iron(II) triﬂate. Oxygenation. Hydrocarbons are oxygenated (e.g., cis-1,2-dimethylcyclohexane to cis-1,2-dimethylcyclohexan-1-ol) using a Fe(II) complex of amine 1 with catalytic amounts of H2O2. The oxygen atom introduced into the hydrocarbon molecules comes from water.1

N N N

Fe(OTf)2 N

(1) H2O2

OH

MeCN H2O

(1) 1

Company, A., Gomez, L., Gu¨ell, M., Ribas, X., Luis, J.M., Que, Jr, L., Costas, M. JACS 129, 15766 (2007).

L Lanthanum. Cyclopropanation.1 Styrenes are cyclopropanated with 1,1-dibromoalkanes in the presence of lanthanum powder and catalytic amounts of iodine in reﬂuxing THF. 1

Nishiyama, Y., Tanimizu, H., Tomita, T. TL 48, 6405 (2007).

Lanthanum chloride. Organolanthanum reagents.1 For nucleophilic addition to easily enolized ketones harder nucleophiles are preferred. Arylithiums, derived from N-Boc arylamines by o,N-dilithiation with t-BuLi, are treated with LaCl3 . 2LiCl in THF before reaction with N-Boc 3-pyrrolidinone to give precursors of Nb-Boc tryptamines.1 La t-BuLi / Et2O LaCl3 · 2LiCl

NHBoc

THF –70°

NBoc O

N

OH

O

NHBoc

NHBoc N H 1

Nicolaou, K.C., Krasovskiy, A., Trepanier, V.E., Chen, D.Y.-K. ACIE 47, 4217 (2008).

Lanthanum tris(hexamethyldisilazide). Carboxamides.1 A mixture of aldehydes and amines are converted into amides at room temperature by treatment with La[N(SiMe3)2]3. The reaction proceeds without added oxidants, bases, and/or heat or light, while one portion of the aldehyde acts as oxidant.

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 271

272

Lanthanum triﬂate

Cyclization. On treatment with La[N(SiMe3)2]3, a 4-alkynol forms the alkoxide which cyclizes to give 2-methylenetetrahydrofuran; the isomer with endocyclic double bond is also formed from 3,4-pentadienol.2 A modiﬁed tris(hexamethyldisilazide) of lanthanum (and of several other rare earth metals) (1) catalyzes intramolecular hydroamination of alkynylamines and the products also undergo hydrosilylation.3

Ph

Ph

SiMe3

Ph P P

NH2

N SiH Ln N SiH N

NSiR'3

(1)

R R

Ph SiMe 3

(1) 1

Seo, S.Y., Marks, T.J. OL 10, 317 (2008). Yu, X., Seo, S.Y., Marks, T.J. JACS 129, 7244 (2007). 3 Rasta¨tter, M., Zulys, A., Roesky, P.W. CEJ 13, 3606 (2007). 2

Lanthanum triﬂate. Nucleophilic addition.1 Hydrated La(OTf)3 is a useful Lewis acid catalyst for the addition of nucleophiles to N-phosphinylimines. In the presence of (CF3CO)2O the N-substitutent is also changed into a triﬂuoroacetyl group.

R

O P Ph N Ph

[Nu] O

La(OTf)3 [NuH] (CF3CO)2O

R

N H

CF3

Imine formation.2 In the presence of La(OTf)3 arylamines condense with aldehydes, further transformation such as electrocyclization may follow. Very poor results are obtained by using Bronsted acids. O NH2

N

H

O

La(OTf)3

OHC

dioxane 100o

+

H NH

N

88% 1

Ong, W.W., Beeler, A.B., Kesavan, S., Panek, J.S., Porco Jr, J.A. ACIE 46, 7470 (2007). Gaddam, V., Nagarajan, R. OL 10, 1975 (2008).

2

Lithium – liquid ammonia

273

Lithium. Lithium organoferrates.1 Ferrocene is reduced by lithium in DME in the presence of COD to form Li(dme)[CpFe(cod)]. The salt is useful for promoting intramolecular ene reaction and [5þ2]cycloaddition. H

Z

Z

(dme)Li[CpFe(cod)] PhMe Δ

H

R

R

Z Z (dme)Li[CpFe(cod)] PhMe Δ

R

R

Reductive coupling.2 Cycloheptatriene gives a dimeric silylcycloheptadiene on treatment with Li and Me3SiCl. Me3Si H 2

Li / Me3SiCl

H SiMe3

1

Fu¨rstner, A., Majima, K., Martin, R., Krause, H., Kattnig, E., Goddard, R., Lehmann, C.W. JACS 130, 1992 (2008). 2 Aouf, C., El Abed, D., Giorgi, M., Santelli, M. TL 48, 4969 (2007).

Lithium – liquid ammonia. Reductive cleavage.1 Certain cyclic sulfonamides suffer double cleavage of CZS and NZS bonds, but an N-benzyl group is more labile. H NR S O Ph O

NH3 (l ); NH4Cl

NH S O Ph O R = Bn

1

H

H Li

Kelleher, S., Muldoon, J., Mu¨ller-Bunz, H., Evans, P. TL 48, 4733 (2007).

NH Ph R = i-Bu

274

Lithium aluminum hydride – niobium(IV) chloride

Lithium aluminum hydride – niobium(IV) chloride. Hydrodeﬂuorination. A triﬂuoromethyl group of bis(triﬂuoromethyl)arenes is converted into the methyl group on heating with LAH (3 equiv.) and NbCl5 (5 mol%) in DME. By increasing the amount of LAH to 10 equivalents both triﬂuoromethyl groups are reduced.1 CF3

CH3 LiAlH4 – NbCl5 DME 85o

CF3

CF3

o-Triﬂuoromethylstyrenes cyclize to give indenes (yields around 60%) under similar conditions.2 CF3

LiAlH4 – NbCl 5

R'

dioxane 100 o

R

R'

R

1

Fuchibe, K., Ohshima, Y., Mitomi, K., Akiyama, T. OL 9, 1497 (2007). Fuchibe, K., Mitomi, K., Akiyama, T. CL 36, 24 (2007).

2

Lithium aluminum hydride – selenium. Amide formation.1 Carboxamides including peptides are synthesized from carboxylic acids and alkyl azides, after converting the acids into mixed anhydrides and then selenocarboxylates. Treatment of the mixed anhydrides with a suspension of freshly prepared from LAH and Se completes the ﬁrst stage of the transformation. 1

Wu, X., Hu, L. JOC 72, 765 (2007).

Lithium borohydride. Reductive amination.1 LiBH4 is said to be the reagent of choice for reductive amination of substituted cyclohexanones. 1

Cabral, S., Hulin, B., Kawai, M. TL 48, 7134 (2007).

Lithium chloride. Mannich reaction. Mukaiyama-type Mannich reaction1 can be effected by LiCl (0.2 equiv.) in DMF. 1

Hagiwara, H., Iijima, D., Awen, B.Z.S., Hoshi, T., Suzuki, T. SL 1520 (2008).

Lithium diisopropylamide, LDA

275

Lithium di-t-butylbiphenylide. Reductive lithiation. Phthalans are cleaved to give O,C-dilithio products which are readily quenched by electrophiles. The direction of cleavage is governed by substituents of the aromatic ring.1

Ph

Ph Li–DTTB

O

Li OLi

THF –78° ~ –50°

Ph

Li–DTTB

O

Ph

OLi Li

THF –78° ~ –50°

OMe

OMe Li–DTTB

O

OLi Li

THF –78° ~ –50°

MeO

MeO

Li–DTTB

O

Li OLi

THF –78° ~ –50°

1

Garcia, D., Foubelo, F., Yus, M. T 64, 4275 (2008).

Lithium diisopropylamide, LDA. Condensation. Condensation involving a carboxamide and an acylsilane (e.g., effected by LDA) proceeds via a Brook rearrangement to generate a b-siloxy homoenolate.1 Trapping by a phosphinylimine leads to product that is convertible to g-lactams.2

O +

Me2N R

Ph O Me3Si

+

R'

THF

NPOPh2

O Ph

LDA

Me2N R

OH R' NHPOPh2

276

Lithium diisopropylamide, LDA

Quaterized a-alkylthiopropargylamines are dimerized to give enediynes that bear thio-substituents on the central double bond. Cyclic products are obtained from the intramolecular version.3

NMe3

Me3Si

S

Me3Si

S

LDA

Me3Si

S NMe3

S Me3Si

2 TfO

48%

Cleavage of allenylidenecyclopropanes.4 2,2-Diaryl-1-allenylidenecyclopropanes react in several different ways upon deprotonation at the cyclopropane. Hydroxyalkylation occurs at the central carbon of the original allene unit with aldehydes, but at a higher temperature the ring is ruptured accompanied by attack on ketones. Still a third type of products arises from reaction with conjugated carbonyl compounds. Electronic effects probably are responsible for the diverse results. O Ar

Ar

Ar

C

Ar O

Ar LDA

Ar

–78°

Ar

Ar

Ar

Ar

C

–41°

Li

Ar Ar

C

Li –78° R'CHO

RR Ar

R' HO

—O R2C—

Ar Ar

C

OH Ar Ar

Ar

Cycloisomerization.5 2-Iodoethyl propargyl ethers give 3-iodomethylenetetrahydrofurans after exposure to substoichiometric amounts of LDA at room temperature.

Lithium diisopropylamide, LDA

277

However, neither the all carbon analog nor 3-iodopropyl propargyl ethers show similar reactivity. Cycloisomerization of iodopropargyl ethers is induced by 1-hexynyllithium.

R

R

CHI

LDA / THF

O

25o

O

I

I

R R

I

I

LDA / THF

O I

25o

O

Y Y Y = H, OEt

Annulated pyrroles.6 1-Dialkylamino-(nþ3,nþ3)-dichlorobicyclo[n.1.0]alkanes suffer dehydrochlorination, to generate, plausibly, allylic chlorocarbenes for subsequent H-abstraction, cyclization and aromatization.

Cl LDA / THF

Cl

N

N

66%

Substitutions. Enolates generated from methyl ketones on treatment with LDA attack dimethyl 2-bromomethylfumarate in an SN20 fashion, to give substitued itaconic esters.7

MeOOC + R

O

Br COOMe

MeOOC

COOMe

LDA

COOMe

–78°

R

O

O R

O

Deprotonation. Regioselective metallation of unsymmetrical 1,3-disubstituted allenes enables homologation. Thus lithiation followed by transmetallation with ZnBr2 and Negishi coupling serves to introduce a new organic residue into the nonbenzylic position.8

278

Lithium diisopropylamide, LDA

Ar

Ar

LDA;

C

ZnBr

ZnBr2

R

Ar

R'I

C

R' C

(Ph3P)4Pd

R

R

Twice deprotonated species from a 3-nitropropanoic ester is used in a double Michael reaction on 4,4-dimethoxy-2,5-cyclohexadienone to furnish bridged ring products (for a synthesis of gelsemine). The deprotonation is conveniently carried out with LDA in THF containing HMPA.9

EtOOC

MeO

LDA

O + MeO

THF HMPA

NO2

O2N MeO

E O

NO2 O

E + MeO

OMe

OMe E = COOEt

The kinetic enolate of a conjugated ketone generated by LDA reacts with a conjugated acylsilane to form the monosilylated 1,3-cycloheptanedione. A Brook rearrangement following the initial C-acylation delivers an allyl anion that is poised to return an attack on the enone that re-emerges.10

O

O

OBn

Si

+

–80° ~ 25°

O

H

LDA

O

O Si

H

Si Ph

OBn

O

Ph

Si

76%

1

Lettan II, R.B., Reynolds, T.E., Galliford, C.V., Scheidt, K.A. JACS 128, 15566 (2006). Lettan II, R.B., Woodward, C.C., Scheidt, K.A. ACIE 47, 2294 (2008). 3 Murai, T., Fukushima, K., Mutoh, Y. OL 9, 5295 (2007). 4 Lu, J.-M., Shi, M. OL 10, 1943 (2008). 5 Harada, T., Muramatsu, K., Mizunashi, K., Kitano, C., Imaoka, D., Fujiwara, T., Kataoka, H. JOC 73, 249 (2008). 6 Bissember, A.C., Phillis, A.T., Banwell, M.G., Willis, A.C. OL 9, 5421 (2007). 7 Baag, M.M., PurNIK, V.G., Argade, N.P. JOC 72, 1009 (2007). 8 Zhao, J., Liu, Y., Ma, S. OL 10, 1521 (2008). 9 Grecian, S., Aube, J. OL 9, 3153 (2007). 10 Sasaki, M., Hashimoto, A., Tanaka, K., Kawahata, M., Yamaguchi, K., Takeda, K. OL 10, 1803 (2008). 2

Lithium hexamethyldisilazide, LHMDS

279

Lithium hexamethyldisilazide, LHMDS. Tandem cyclization. Using LHMDS as base the tetracyclic precursor of pareitropone is constructed from a biaryl. After addition of the tosylamide anion to an iodonioalkyne triple bond to generate an alkylidenecarbene, addition across an aromatic ring follows.1 O

OTIPS

OTIPS (Me3Si)2NLi

IPh MeO

TfO

MeO

NHTs

DME –40°

MeO

MeO

NTs

N

MeO

MeO

pareitropone

Wittig rearrangement. Functionalized 1,2-amino alcohols are acquired from 3-tosylamino-2-propen-1-yl ethers by Wittig rearrangement.2 Interesting stereoselectivity of the reaction depending on the substituent of the alkyl component has been revealed. SiR'3

R

Ts N

SiR'3 LDA / THF –78°

O

R

Ts N

OH

anti: syn 11->24 : 1

R

Ts N

O

O LiHMDS

N

R

THF, HMPA

O

Ts N

N OH

anti: syn 1 : 9->24

Dehydroalkylation. a-Keto amides are enolized and reaction of the resulting enediolate species with alkyl iodides furnishes 2-hydroxy-3-alkenamides.3 OLi O

NLi

N

R O

R N

LiCl / THF 0o

HO OLi

R' O

R R'I

N

280

Lithium naphthalenide, LN

Cyclopropanation. Ylides derived from 2-cyanoazetidinium triﬂates behave as stabilized carbenoids that cycloadd to enones.4 Ph

Ph CN

O H

O

LiHMDS

H

CN

N

N Me2N

TfO

CN Ph 91%

1

Feldman, K.S., Cutarelli, T.D. JACS 124, 11600 (2002). 2 Barbazanges, M., Meyer, C., Cossy, J. OL 9, 3245 (2007). 3 Marsden, S.P., Newton, R. JACS 129, 12600 (2007). 4 Couty, F., David, O., Larmanjat, B., Marrot, J. JOC 72, 1058 (2007).

Lithium naphthalenide, LN. Halogen/lithium exchange. LN enables exclusive conversion of sp-hybridized CZCl and CZBr bond in the presence of sp 3-hybridized CZCl bond, but sp 3-hybridized CZI bond undergoes I/Li exchange preferentially to an sp-hybridized C-Cl bond.1 It is also possible to exchange an sp 2-hybridized C-bonded Br in preference to an sp 3-hybridized C-bonded Cl. 1

Abou, A., Foubelo, F., Yus, M. T 63, 6625 (2007).

Lithium 2,2,6,6-tetramethylpiperidide, LiTMP. Metallation. 5-Membered heterocycles are metallated by LiTMP, and transmetallated in the presence of ZnCl2-TMEDA.1 Remarkably regioselective lithiation of 3-methylthiophene at C-5 (79 : 1 over C-2) is observed with LiTMP in THF at –78o. (Cf. 3 : 1 and 5 : 1 in lithiation with MeLi and t-BuLi, respectively.)2 a-(N-Boc-N-bromoalkyl)amino esters cyclize on treatment with an alkali metal amide. Remarkably, enantiodivergence is observed on changing the base.3 R LiTMP THF (inversion)

R Boc

EtOOC N

Boc

COOEt N

Br EtOOC KN(SiMe3)2 DMF (retention)

R Boc

N

Lithium triﬂimide

Alkene synthesis. alkenes.4

281

Exposure of epoxides to RM (M ¼ Li, MgX) and LiTMP leads to

NLi

O R

+ R'Li

hexane

R

R'

0° ~ 22°

1

L’Helgoual’ch, J.-M., Seggio, A., Chevallier, F., Yonehara, M., Jeanneau, E., Uchiyama, M., Mongin, F. JOC 73, 177 (2008). 2 Smith, K., Barratt, M.L. JOC 72, 1031 (2007). 3 Kawabata, T., Matsuda, S., Kawakami, S., Monguchi, D., Moriyama, K. JACS 128, 15394 (2006). 4 Hodgson, D.M., Fleming, M.J., Stanway, S.J. JOC 72, 4763 (2007).

Lithium triethylborohydride. Reduction.1 This borohydride reduces nitriles to afford stable aldimine-borane complexes, which can be used to prepare homoallylic amines on further reaction with R2BCH2CHvCH2. 1

Ramachandran, P.V., Biswas, D. OL 9, 3025 (2007).

Lithium triﬂimide. Aminolysis. The conversion of lactones by reaction with amines to v-hydroxy amides is catalyzed by LiNTf2.1 1

Lalli, C., Trabocchi, A., Menchi, G., Guarna, A. SL 189 (2008).

M Magnesium. Deoxygenation. Oxides of diorganochalcogenides (S, Se, Te) are deoxygenated by Mg in MeOH at room temperature. Both monoxides and dioxides are affected.1 Polysilanes.2 Dichlorosilanes are reductively polymerized on treatment with Mg and a Lewis acid and LiCl. Reformatsky reaction.3 As an alternative promoter to zinc metal, the use of Mg-FeCl3 or Mg-CuCl2 . 2H2O has been demonstrated. Reductive acylation. Treatment of anthracene and a dicarboxylic acid chloride with magnesium in DMF leads to the dibenzo bridged diketone product.4 Indole synthesis.5 Intramolecular sp 2-sp 3 coupling mediated by Mg is applied to synthesis of 2-ﬂuoroalkylindoles. R

R Br

N RF

+

Mg

THF

RF N H

Cl

1

Khurana, J.M., Sharma, V., Chacko, S.A. T 63, 966 (2007). Kashimura, S., Tane, Y., Ishifune, M., Murai, Y., Hashimoto, S., Nakai, T., Hirose, R., Murase, H. TL 49, 269 (2008). 3 Chattopadhyay, A., Dubey, A.K. JOC 72, 9357 (2007). 4 Matsunami, M., Sakai, N., Morimoto, T., Maekawa, H., Nishiguchi, I. SL 769 (2007). 5 Ge, F., Wang, Z., Wan, W., Hao, J. SL 447 (2007). 2

Magnesium bromide etherate. C-Acylation. Condensation of ketones with acylating agents such as 1-acylbenzotriazoles is readily accomplished on treatment with MgBr2 . OEt2 and i-Pr2NEt. Additive aldol reaction.2 An anti-selective synthesis of S-phenylthio esters of 3-hydroxy-2-phenylthiomethylalkanethiolates from a mixture of acryloyl chloride, PhSLi and aldehydes is mediated by MgBr2 . OEt2.

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 283

284

Magnesium iodide

OH O MgBr2 · OEt2

COCl RCHO

+

+

PhSLi

SPh

R

CH2Cl2

SPh

Radical addition. A highly stereoselective addition of alkyl radicals to acrylic esters has been reported. The presence of MgBr2 . OEt2 seems critical.3 C5H11I

OBn EtOOC

COOEt

C5H11

OBn

C5H11

Bu3SnH–Et 3B MgBr2 · OEt 2

EtOOC

–60°

COOEt 59%

1

Lim, D., Fang, F., Zhou, G., Coltart, D.M. OL 9, 4139 (2007). Zhou, G., Yost, J.M., Sauer, S.J., Coltart, D.M. OL 9, 4663 (2007). 3 Nagano, H., Kuwahara, R., Yokoyama, F. T 63, 8810 (2007). 2

Magnesium iodide. Isomerization. N-Aryl-2-alkylidenecyclopropanecarboxamides undergo isomerization to give b-alkylidene-g-lactams on treatment with MgI2 in THF.1 1

Scott, M.E., Schwarz, C.A., Lautens, M. OL 8, 5521 (2006).

Magnesium oxide. Double Michael addition. In the presence of MgO alkynyl ketones and 1,3-propanedithiol react to afford 2-acylmethyl-1,3-dithianes.1 1

Xu, C., Bartley, J.K., Enache, D.I., Knight, D.W., Lunn, M., Lok, M., Hutchings, G.J. TL 49, 2454 (2008).

Magnesium perchlorate. Alkylidenation.1 Condensation of b-diketones with aldehydes is catalyzed by Mg(ClO4)2. Transfer hydrogenation.2 1-Acetyl-2,3-dimethylimidazolidine acts as H donor in MeCN-MeOH in the presence of Mg(ClO4)2 to reduce aromatic aldehydes, their imino derivatives (ArCHvNPh, ArCHvNTs) and cinnamaldehydes to give the corresponding alcohols and amines. 1

Bartoli, G., Bosco, M., Carlone, A., Dalpozzo, R., Galzerano, P., Melchiorre, P., Sambri, L. TL 49, 2555 (2008). 2 Li, D., Zhang, Y., Zhou, G. SL 225 (2008).

Magnesium 2,2,6,6-tetramethylpiperidide. Magnesiation. The magnesium amide (as LiCl complex) is very useful for o-magnesiation of aroic esters1 and aryl bis(dimethylamido)phosphates.2 Reaction of the

Manganese

285

magnesiated species with electrophiles leads to products of substitution patterns otherwise difﬁcult to achieve. O

O

O

N 2

O

O

Mg

O

Mg

N

–40°

1

Clososki, G.C., Rohbogner, C.J., Knochel, P. ACIE 46, 7681 (2007). Rohbogner, C.J., Clososki, G.C., Knochel, P. ACIE 47, 1503 (2008).

2

Mandelic acid. Alcoholysis. Styrene oxides open on treatment with ROH in the presence of mandelic acid and N,N0 -di[3,5-bis(triﬂuoromethyl)phenyl]thiourea in a regioselective manner, due to cooperative interaction of the Bronsted acids.1 F3C CF3 O

Ph

H N S

Ar O

O

H O

H N

H

CF3 F3C

1

Weil, T., Kleiner, C.M., Schreiner, P.R. OL 10, 1513 (2008).

Manganese. Conjugated esters. Active Mn is prepared from MnCl2 via Li2MnCl4 and treating the latter with Li and 2-phenylpyridine. The active metal promotes reaction of 2,2-dichloroalkanoic esters with aldehydes to furnish conjugated esters.1 Cl RCHO

+

COOR"

Cl

THF

Li2MnCl4

1

R'

Li

R'

COOR"

R

Mn*

+ N

Ph

Concellon, J.M., Rodriguez-Solla, H., Diaz, P., Llavona, R. JOC 72, 4396 (2007).

286

Manganese(III) acetate

Manganese(III) acetate. Oxidation. Aporphines undergo demethylative aromatization and further oxidation at ring C on exposure to Mn(OAc)3.1 R

R NMe

MeO

Mn(OAc)3

N

MeO

O MeO

MeO

R

R

Oxidative cyclization. 4-Pentenylmalonic esters give bicyclic lactones in moderate to good yields when exposed to Mn(OAc)3 and Cu(OTf)2.2 O

MeOOC

COOMe R"

R

Mn(OAc)3

O

MeOOC R

R" H

Cu(OTf)2

R

R

R

R

A dramatic solvent effect has been observed in the following radical cyclization.3 For reproducibly good yields 2,2,2-triﬂuoroethanol is used.

O

OTBS H

EtOOC

H

O EtOOC

O

O

H

Mn(OAc)3

H H

OTBS

Cu(OAc)2

H HO

CF3CH2OH–HOAc

O

(10 : 1)

O H O

50%

No copper-based cooxidant is required in the oxidative cyclization of N-acylindoles such as shown below.4 O

R

O

O

R

Mn(OAc)3

N H O

R'

HOAc Δ

N

O R'

O R = Me, R' = OMe 55% R = R' = Me 60%

Mercury(II) triﬂate

287

Phosphonation.5 Heteroaryl compounds (furans, pyrroles, thiazoles, . . .) undergo Mn(III)-mediated regioselective phosphonation with HP(O)(OMe)2. 1

Singh, O.V., Huang, W.-J., Chen, C.-H., Lee, S.-S. TL 48, 8166 (2007). Powell, L.H., Docherty, P.H., Hulcoop, D.G., Kemmitt, P.D., Burton, J.W. CC 2559 (2008). 3 Toueg, J., Prunet, J. OL 10, 45 (2008). 4 Magolan, J., Carson, C.A., Kerr, M.A. OL 10, 1437 (2008). 5 Mu, X.-J., Zou, J.-P., Qian, Q.-F., Zhang, W. OL 8, 5291 (2006). 2

Manganese(II) triﬂate. Epoxidation.1 Various alkenes are epoxidized by peracetic acid with a complex of Mn(OTf)2 to triazanonane 1 as catalyst.

N N Mn(OTf)2 N

N

(1) 1

Garcia-Bosch, I., Company, A., Fontrodona, X., Ribas, X., Costas, M. OL 10, 2095 (2008).

Mercury(II) triﬂate. Hydration-elimination. Addition of water (1 equiv.) to 3-acetoxy-1-ethoxyalkynes results in the formation of conjugated esters. A convenient catalyst is Hg(OTf)2, which dictates the production of the (E)-isomers.1 Cyclodehydation. 6-Aryl-2-hexenols cyclize on brief heating with catalytic amounts of Hg(OTf)2 in toluene.2

MeO

MeO

MeO Hg(OTf)2 PhMe Δ

OH

HgOTf OH

96%

N-Tosylindolines.3 Activation of the triple bond of N-tosyl-2-[2-(4-pentynoyloxy)ethyl]anilines by Hg(OTf)2 triggers cyclization. Benzologous pentynoic esters react similarly.

288

Mesityltriphenylbismuthonium tetraﬂuoroborate

O

O

Hg(OTf)2

O

NHTs

CH2Cl2

O NH Ts

+

O

N Ts 96%

Hg(OTf)2

+

0o

O

O

N Ts

O

80% 1

Nishizawa, M., Hirakawa, H., Nakagawa, Y., Yamamoto, H., Namba, K., Imagawa, H. OL 9, 5577 (2007). 2 Namba, K., Yamamoto, H., Sasaki, I., Mori, K., Imagawa, H., Nishizawa, M. OL 10, 1767 (2008). 3 Yamamoto, H., Pandey, G., Asai, Y., Nakano, M., Kinoshita, A., Namba, K., Imagawa, H., Nishizawa, M. OL 9, 4029 (2007).

Mesityltriphenylbismuthonium tetraﬂuoroborate. Oxidation.1 The title compound is an oxidant for primary and secondary alcohols. Oxidation is carried out with the base tetramethylguanidine at room temperature, liberating mesitylene and Ph3Bi as side products. 1

Matano, Y., Suzuki, T., Shinokura, T., Imahori, H. TL 48, 2885 (2007).

Methanesulfonic acid. Isomerization.1 1-Alken-3-ols undergo isomerization to afford 2-alken-1-ols on treatment with MsOH in aq.THF.1 1-Amino-2-alkanols.2 Terminal epoxides are opened by NH3 (in saturated EtOH) regioselectively. To render the procedure operationally simple and cost-effective, ﬁve equivalents of MsOH are added. Cyclization.3 A critical step in a synthesis of (-)-cribrostatin-4 is the closure of the azabicyclo unit by treatment of an aldehyde precursor with MsOH. The reaction is very sensitive to the concentration of the acid catalyst and solvent. OMe

OH O

SC6H13 H CHO

OH

O

O N

N

MeO OH BnO

OMe

HO

OMe

NHAlloc

N

MeO

O

OH BnO

MsOH 0.01%

Alloc

N

+

N

MeO OH BnO

O

major

minor

0.1% in CH 2Cl2

2 : 3

0.1% in MeCN

1 : 10

O

Alloc

Molybdenum(VI) dichloride dioxide

289

1

Leleti, R.R., Hu, B., Prashad, M., Repic, O. TL 48, 8505 (2007). Kaburagi, Y., Kishi, Y. TL 48, 8967 (2007). 3 Chen, X., Zhu, J. ACIE 46, 3962 (2007). 2

Methylaluminum bis(2,6-di-t-butyl-4-methylphenoxide), MAD. Ring expansion.1 2-Methylenecyclopropanecarboxamides undergo expansion on reaction with N-tosylaldimines under the inﬂuence of a Lewis acid and with the assistance of iodide ion. Due to steric effects the reactions promoted by MAD–Bu4NI and by MgI2 lead to isomeric products. CONR2 Al CONR2

O

MAD

NR2

Bu4NI

MAD = MeAl

O

TsN

TsN

I

R'

R'

2

Rearrangement.2 (1Z,3E)-Alkadienyl acetals are convertd into 2-(a-alkoxy)alkyl-3alkenals on treatment with MAD or ATPH. The rearrangement is a-regioselective. R'

R' MAD

R

CH2Cl2

O

R OHC

O

O

1

Taillier, C., Bethuel, Y., Lautens, M. T 63, 8469 (2007). Tayama, E., Hashimoto, R. TL 48, 7950 (2007).

2

N-Methyl-2-benzyloxypyridinium triﬂate. Friedel– Crafts benzylation.1 The title salt is a stable precursor of benzylcarbenium ion. On thermolysis (at 808) of its mixture with an electron-rich arene the cation is generated and trapped. 1

Albiniak, P.A., Dudley, G.B. TL 48, 8097 (2007).

Molybdenum(VI) dichloride dioxide. b-Keto esters.1 For condensation of diazoacetic esters with aldehydes to furnish b-keto esters MoO2Cl2 is an effective catalyst. 1

Jeyakumar, K., Chand, D.K. S 1685 (2008).

290

Molybdenum hexacarbonyl

Molybdenum hexacarbonyl. Acylation. Formation of bicyclic lactams related to the Pauson–Khand reaction is realized from 5,6-alkadienal hydrazones by heating with Mo(CO)6 and DMSO in CH2Cl2 at 1008.1 With thiocarbonyl compounds the reaction leads to thiolactones.2 H C Z

Z O

O N H N

Mo(CO)6 DMSO CH2Cl2 100o

N N

O

O

O 57–91%

Z = O, NTs, CH 2, C(COOEt)2

R

R

O

[(cod)RhCl]2

N

C

S

+

CO

S

DPPP o DMSO 115

N

Coupling of electron-deﬁcient ArI and 1-alkynes while incorporating CO to provide alkynyl aryl ketones is accomplished at room temperature by a Pd-catalyzed reaction with Mo(CO)6.3 O Mo(CO)6

Ar-I

+

R

Ar

(t-Bu3P)2Pd

R

Et3N / MeCN

Ketone formation from aryl and alkenyl halides via carbonylation and addition to alkenes is accomplished by heating the substrates with Mo(CO)6 in DMF at 1608.4 The (dmf)3Mo(CO)3 modiﬁcation furnishes CO to combine with an aldehyde and a triple bond to form a butenolide unit.5 R

R CHO O

(dmf)3Mo(CO)3 THF

H O

O

O

Chain elongation of ArCHO. Transformation of ArCHO to 2-arylidene derivatives of Meldrum’s acid followed by reduction with PhSiH3 accomplishes homologation of the aldehydes by two carbon units. The second step is catalyzed by Mo(CO)6.6

Molybdenum hexacarbonyl

O

O O

Ar

O

O C

Mo(CO)6

OSiPh3

Ar

OSiPh3

CHO

O

O

NMO 80o

291

Ar

OSiPh3

Ar

+ Ph3SiH

Reductive cleavage. Pentaﬂuorophenyl isoxazolidine-4-sulfonates are converted into a-hydroxymethyl-b-sultams on treatment with Mo(CO)6 in aqueous MeCN at 908. Cyclization occurs after the N-O bond is cleaved.7 O O C6F5O S

O N S O

Mo(CO)6

R

1

N

O

MeCN, H2O 90o

R

OH

Kim, S.-H., Kang, E.S., Yu, C.-M. SL 2439 (2007). Saito, T., Nihei, H., Otani, T., Suyama, T., Furukawa, N., Saito, M. CC 172 (2008). 3 Iizuka, M., Kondo, Y. EJOC 5180 (2007). 4 Sangu, K., Watanabe, T., Takaya, J., Iwasawa, N. SL 929 (2007). 5 Adrio, J., Carretero, J.C. JACS 129, 778 (2007). 6 Frost, C.G., Hartley, B.C. OL 9, 4259 (2007). 7 Lewis, A.K.deK., Mok, B.J., Tocher, D.A., Wilden, J.D., Caddick, S. OL 8, 5513 (2006). 2

N Naﬁon resin. Photochemical reactions. The Naþ-form resin is found to be an excellent reaction medium for photo-induced cyclization of a-pyridone derivatives to provide bicyclic b-lactams.1 Deprotection. Terminal acetonides and trityl ethers are selectively cleaved on exposure to Naﬁon-H in MeOH at room temperature.2 1

Arumugam, S. TL 48, 2461 (2008). Rawal, G.K., Rani, S., Kumar, A., Vankar, Y.D. TL 46, 9117 (2006).

2

Nickel. Reductions. In reﬂuxing isopropanol carbonyl compounds are reduced in the presence of nickel nanoparticles.1 Reductive amination is also performed under the same conditions.2 Catalytic hydrogenation of alkenes and alkynes is achieved with nickel nanoparticles prepared from NiCl2 by reduction with Li and catalytic amounts of DTBB and an alcohol.3 1

Alonso, F., Riente, P., Yus, M. T 64, 1847 (2008). Alonso, F., Riente, P., Yus, M. SL 1289 (2008). 3 Alonso, F., Osante, I., Yus, M. T 63, 93 (2007). 2

Nickel, Raney. Pyrazoles. Isoxazoles are readily converted into pyrazoles on treatment with hydrazine at room temperature in the presence of Raney nickel.1 1

Sviridov, S.I., Vasil’ev, A.A., Shorshnev, S.V. T 63, 12195 (2007).

Nickel(II) acetate. Aminocarbonylation.1 A method for preparation of ArCONMe2 from ArX involves heating with DMF and NaOMe in dioxane. The catalyst system contains Ni(OAc)2 . 4H2O and [2,4-(t-Bu)2C6H3O]3P. 1

Ju, J., Jeong, M., Moon, J., Jung, H.M., Lee, S. OL 9, 4615 (2007).

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 293

294

Nickel(II) acetylacetonate

Nickel(II) acetylacetonate. Coupling. A route to biaryls entails the use of Ni(acac)2 to couple ArX with Ar0 Ti(OEt)3.1 A hindered phosphine or carbene ligand is also added. N-Arylation. Secondary amines are arylated by ArCl under the following conditions: heating with Ni(acac)2, 3,5,6,8-tetrabromo-1,10-phenanthroline, sodium t-butoxide, and PMHS in toluene at 1308.2 Addition. Diorgano dichalcogenides are split and add to 1-alkynes to afford (Z)-1,2bis(organochalcogeno)-1-alkenes. Better results are obtained on using Ni(acac)2 – PhPMe2 than (dba)3Pd2 – PhPCy2 although excess alkynes are required.3 1

Manolikakes, G., Dastbaravardeh, N., Knochel, P. SL 2077 (2007). Manolikakes, G., Gavryushin, A., Knochel, P. JOC 73, 1429 (2008). 3 Ananikov, V.P., Gayduk, K.A., Beletskaya, I.P., Krustalev, V.N., Antipin, M.Yu. CEJ 14, 2420 (2008). 2

Nickel(II) acetylacetonate–diorganozinc. Reductive aldol reaction.1 Conjugated amides with N-acylalkyl substituents are liable to cyclize on treatment with Ni(acac)2 – Et2Zn, with the organozinc reagent serving as a reducing agent to generate the amide enolates. Often inferior results are obtained when Co(acac)2 – Et2Zn is employed. O

O

R' O

NR

Et2Zn Ni(acac)2

R"

R' HO R"

NR

Cyclization.2 1,6-Enynes afford alkylidenecyclopentanes as exempliﬁed by the following equation. R

R Z

i-Pr2 Zn

Ni(acac)2

Z

THF 40o

1

Joensuu, P.M., Murray, G.J., Fordyce, E.A.F., Luebbers, T., Lam, H.W. JACS 130, 7328 (2008). Chen, M., Weng, Y., Guo, M., Zhang, H., Lei, A. ACIE 47, 2279 (2008).

2

Nickel bromide. Propargylarenes.1 Secondary benzylic bromides couple with trialkynylindium reagents in the presence of (diglyme)NiBr2. An enantioselective version employing a Pybox ligand leads to chiral products in about 80% ee. 1

Caeiro, J., Sestelo, J.P., Sarandeses, L.A. CEJ 14, 741 (2008).

Nickel chloride

295

Nickel bromide–zinc. Cycloaddition. Formation of [a,e]-fused cyclooctatetraenes by cyclodimerization of terminal diynes in a formal [2þ2þ2þ2]cycloaddition is effected by (dme)NiBr2 –Zn.1

2

Zn (dme)NiBr2

Z

Z

Z

THF 60o

Reductive coupling. Certain b-amino esters are synthesized from imines and acrylic esters, by mediation of (phenanthroline)NiBr2 –Zn.2 Conjugated sulfones, nitriles also couple with the imines. NAr'

COOMe

+

Ar

R

Zn

Ar'NH COOMe

(phen)NiBr2

Ar

MeCN–H2O

R

80o

1

Wender, P.A., Christy, J.P. JACS 129, 13402 (2007). Yeh, C.-H., Korivi, R.P., Cheng, C.-H. ACIE 47, 4892 (2008).

2

Nickel chloride. Coupling reactions. Modiﬁed procedures for the Stille coupling,1 Hiyama coupling,2 and Negishi coupling3 involving aliphatic substrates are based on (dme)NiCl2 promotion. C2-symmetric vic-diamines ligands are employed in the ﬁrst two reaction types and chiral a-branched carboxylic esters are accessible by the method. Allylic chlorides are transformed into chiral products.

R

COOR"

R

(dme)NiBr2

+

R"Si(OMe)3

Ph

Br

MeNH

R'

NHMe

Cl R

R" + R'

+ NaCl

R"'

(dme)NiCl2

R"'ZnBr

R O

O

N

COOR"

Ph

N

N

Bn

Bn

R" R'

From alkenyl triﬂates (or iodides), diorganozincs and CO, conjugated ketones are assembled with the aid of NiCl2.4

296

Nickel iodide

O OTf

NiCl2 –MgBr2

+

R2Zn

+ CO

R

OMe

MeO N

N

(Py)4NiCl2 is a precatalyst for Negishi coupling that is preceded by a cyclization process.5

I Z

ZnBr

+

O

R

H (Py)4NiCl2 THF

R Z

O H

The complex of NiCl2 to both Ph3P and 1,3-bis(2,6-diisopropylphenyl)imidazol2-ylidene promotes a-arylation of alkyl aryl ketones and N-arylation of ArNH2.6 1

Saito, B., Fu, G.C. JACS 129, 9602 (2007). Dai, X., Strotman, N.A., Fu, G.C. JACS 130, 3302 (2008). 3 Son, S., Fu, G.C. JACS 130, 2756 (2008). 4 Wang, Q., Chen, C. TL 49, 2916 (2008). 5 Phapale, V.B., Bunuel, E., Garcia-Iglesias, M., Cardenas, D.J. ACIE 46, 8790 (2007). 6 Matsubara, K., Ueno, K., Koga, Y., Hara, K. JOC 72, 5069 (2007). 2

Nickel iodide. Coupling reactions.1 The Ph3P-complex of NiI2 is found to succor the reaction of o-bromobenzylzinc bromides with alkenes and alkynes, delivering indanes and indenes, respectively.

R' ZnBr

(Ph3P)2NiI2

+

R'

Br R

R

1

Deng, R., Sun, L., Li, Z. OL 9, 5207 (2007).

Nickel perchlorate. Cycloaddition.1 Azomethine imines constituting a segment of heteroaromatic systems are activated toward cycloaddition with cyclopropanes.

2-Nitro-5-piperidinylbenzyl alcohol

N NBz

COOMe

COOMe

+

297

Ni(ClO4)2

N BzN

COOMe R

COOMe

R Perreault, C., Goudreau, S.R., Zimmer, L.E., Charette, A.B. OL 10, 689 (2008).

1

2-Nitrophenyl isocyanide. Ugi reaction.1 As a participant of the Ugi reaction, the title compound provides an active acyl unit for further synthetic transformations such as for the elaboration of fused g-lactam/b-lactones. By reduction and diazotization, the N-(2-nitrophenyl)carboxamide products are converted into N-acylbenzotriazoles.

+

CN NO2

O

O HOOC

RN

O RN

N H

O

NO2

N N N

O

+ RNH2

+

CN NO2

O HOOC

OH

O

HO

RN OH

O

NH NO 2 OH

RN O

O

O

OH

+ RNH2

H

1

Gilley, C.B., Kobayashi, Y. JOC 73, 4198 (2008).

2-Nitro-5-piperidinylbenzyl alcohol. Carboxyl protection.1 Esters of the title reagent 1 are cleaved photochemically under speciﬁc conditions. The nitro group, while existing mainly in the nitronate form due to resonance interaction of the p-amino group, is therefore photoinactive. By addition of TfOH or Cu(OTf)2 to remove the resonance the susceptibility to decomposition by UV light revives. NO2 OH

N

(1) 1

Riguet, E., Bochet, C.G. OL 9, 5453 (2007).

O Organoaluminum reagents. Addition reactions. The 1,2- and 1,4-additions of organoalanes to conjugated carbonyl compounds have been reviewed.1 There is a report on reaction of R3Al with N-diphenylphosphonylketimines.2 Alkynyldimethylalanes are superior reagents for transferring an alkynyl group to N-toluenesulﬁnylimines in comparison with the corresponding lithium and magnesium reagents.3 R' R'

Tol

O S

CH2Cl2

R

+

0o

Tol

AlMe2

O S

R

Conjugated sulfoxides.4 A method for the preparation of conjugated sulfoxides involves reaction of the pyridine-coordinated alkenyldiisobutylalanes with ArSO2Cl in the presence of Ph3P. Aluminum iminoxides.5 Nucleophilic amides are formed upon condensation of esters with amines, which are liable to undergo conjugate addition to enones when catalyzed by Sn(OTf)2. The reaction has found an application in the synthesis of (-)-cephalotaxine. O O

N

Sn(OTf)2

Br MeOOC

OAlMe2

O

Me3Al

NH2

O

Br

DMF

O O O N

O

O Br

O

HO OMe

N

O

(-)-cephalotaxine

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 299

300

Organocerium reagents

Reduction.6 Meerwein–Ponndorf –Verley reduction of 4-pyranones with a reagent derived from Me3Al and benzhydrol favors hydride delivery from tris(diphenylmethoxy)aluminum on the equatorial side to give axial alcohols. R

O

R

R

O

R

Me3Al Ph2CHOH

O

CH2Cl2

OH (major)

Cycloadditions. With Et2AlOEt present, a-chloroalkenyl acetates react with carbonyl compounds and imines to furnish b-lactones and b-lactams, respectively. The ketene equivalent also combines with oximes to give 5-isoxazolidones.7 A synthesis of 4-substituted 1,2,3-triazoles involves reaction of 1-alkynes with diorganoaluminum azides. The inexpensive and nontoxic azide reagents are available from mixing R2AlCl with NaN3 in toluene.8 The carbon acid Tf2CH2 reacts with Me3Al to form Me2AlCHTf2, which is an excellent catalyst for the highly endo-selective Diels–Alder reaction between cyclopentadiene and conjugated lactones.9 Modiﬁed Claisen condensation.10 Silyl ketene acetals and methyl esters (important!) react in the presence of Me3Al in toluene to afford mixed methyl/silyl acetals of b-ketoesters. 1,4-Diynes.11 A synthesis of the skipped diynes from 1-alkynes and propargylic mesylates involves prior conversion of the former compounds into aluminum derivatives. 1

Von Zezschwitz, P. S 1809 (2008). Reingruber, R., Bra¨se, S. CC 105 (2008). 3 Turcaud, S., Berhal, F., Royer, J. JOC 72, 7893 (2007). 4 Signore, G., Calderisi, M., Malanga, C., Menicagli, R. T 63, 177 (2007). 5 Tietze, L.F., Braun, H., Steck, P.L., El Bialy, S.A.A., To¨lle, N., Du¨fert, A. T 63, 6437 (2007). 6 Dilger, A.K., Gopalsamuthiram, V., Burke, S.D. JACS 129, 16273 (2007). 7 Bejot, R., Anjaiah, S., Falck, J.R., Mioskowski, C. EJOC 101 (2007). 8 Aureggi, V., Sedelmeier, G. ACIE 46, 8440 (2007). 9 Yanai, H., Takahashi, A., Taguchi, T. TL 48, 2993 (2007). 10 Iwata, S., Hamura, T., Matsumoto, T., Suzuki, K. CL 36, 538 (2007). 11 Kessabi, J., Beaudegnies, R., Jung, P.M.J., Martin, B., Montel, F., Wendeborn, S. OL 8, 5629 (2006). 2

Organocerium reagents. Tertiary amines from thioamides.1 Alkyldichlorocerium reagents (alkyl group being primary) react with imino thioethers, which are formed by treatment of thioamides with MeOTf.

Organocopper reagents

S R

+

301

MeOTf

MeCeCl2

R

NR'2

NR'2

1

Agosti, A., Britto, S., Renaud, P. OL 10, 1417 (2008).

Organocopper reagents. Arylcuprates.1 Mixed aryl(2-thienyl)cuprate reagents can be prepared from ArTeBu and Me(2-Th)Cu(CN)Li2. Additions. Lithium diorganocuprates R2CuLi (e.g., R ¼ n-Bu) add to the double bond of cyclopropenyl carbinols.2 The stereochemical course of the reaction is different from that employing RMgBr-CuI. R BuCuLi

OH

Et2O –20°; [E]X

Bu

[E]

R OH

Bu

BuMgBr–CuI Et2O 0°; [E]X

[E] R HO

Benzaldimines are readily cuprated at the a-position of the N-alkyl substituent via lithiation and treatment with PhSCu. When an o-position of the benzene ring carries an alkynyl group, cyclization to give benzazepines occurs.3 N

R

N LDA; PhSCu;

R

NH4Cl, H2O

R'

R'

A new application of the conjugate addition of lithium diorganocuprates to enals is found in a synthesis of (-)-grandisol.4

CHCHO O O

Me2CuLi

CHO

OH

Et2O –78°

O O 97%

(-)-grandisol

302

Organogallium reagents

A synthesis of 3,4-disubstituted b-prolines from a-(allylaminomethyl)acrylic esters is initiated by conjugate addition.5 Participation of the unactivated double bond at the second stage of the transformation is remarkable. [E] RCu(CN)ZnBr;

Bn

R

[E]+

N

COOMe

Bn

N

COOMe

Cupration. Arylcopper reagents are formed with the Cu atom attached to a functional group (e.g., alkoxy, amide, cyano, . . .) of an arene, on treatment with R(TMP)Cu(CN)Li2 derived from (1). Such copper reagents can engage in hydroxylation, phenylation, alkylation, acylation, silylation, and dimerization.6

Li N

N C

Li

Cu

N

N

(1) Substitution. Reaction of the diepoxides derived from allenes with organocuprates to afford a-hydroxy ketones is stereoselective.7 20 : 1 C R

R'

O

O

H

O R R'

MeCu(CN)Li

R

8:1 R'

OH

1

Toledo, F., Cunha, R.L.O.R., Raminelli, C., Comasseto, J.V. TL 49, 873 (2008). Simaan, S., Marek, I. OL 9, 2569 (2007). 3 Lyaskovskyy, V., Bergander, K., Fro¨hlich, R., Wu¨rthwein, E.-U. OL 9, 1049 (2007). 4 Bernard, A.M., Frongia, A., Ollivier, J., Piras, P.P., Secci, F., Spiga, M. T 63, 4968 (2007). 5 Denes, F., Perez-Luna, A., Chemla, F. JOC 72, 398 (2007). 6 Usui, S., Hashimoto, Y., Morey, J.V., Wheatley, A.E.H., Uchiyama, M. JACS 129, 15102 (2007). 7 Ghosh, P., Lotesta, S.D., Williams, L.J. JACS 129, 2438 (2007). 2

Organogallium reagents. Condensation reactions. 1-Alkynes combine with aldehydes to afford propargylic alcohols. The condensation can be mediated by Me3Ga in CH2Cl2 at room temperature.1

Organolithium reagents

303

Wittig reaction of propargylphosphonium salts with aldehydes is (Z)-selective using Me3Ga as base. From the analogous sulfonium salts, alkynyl epoxides are obtained (base: t-Bu3Ga).2 Me3Ga

Et3Si

+

PPh3

Br

RCHO

Et3Si

THF 0o

R t-Bu3Ga

Et3Si

+ RCHO

SMe2

Br

Et3Si

O

THF 25o

R

1

Jia, X., Yang, H., Fang, L., Zhu, C. TL 49, 1370 (2008). Nishimura, Y., Shiraishi, T., Yamaguchi, M. TL 49, 3492 (2008).

2

Organoindium reagents. Cyclization. Organoindium reagents participate in a Pd-catalyzed reaction of an allylic ester that contains a triple bond at some distance by addition, leading to a cyclic compound (with a 5- or 6-membered ring).1 AcO

R

R' +

R

(dba)2Pd

R3In

DMF

80o

X

X

1

Metza J.T., Jr, Terzian, R.A., Minehan, T. TL 47, 8905 (2006).

Organolithium reagents. 2-Arylethanols. A straightforward preparation of ArCH2CH2OH consists of mixing ArLi with ethylene sulfate.1 Alkenylsilanes. Bis(trimethylsilyl)methyllithium is formed by Cl/Li exchange from reaction of (Me3Si)2CHCl with s-BuLi. A Peterson reaction leads to (E)-alkenylsilanes.2 Nucleophilic reactions. 2-Lithio-1,3-dithianes are found to add to styrenes and stilbenes.3 Access to mononuclear Fischer carbene complexes is realized by the reaction of organolithiums to the CO ligand followed by O-alkylation.4

S S

Ar

+

S

Li R

Li

S

R'

Ar R

R'

304

Organolithium reagents

XR

XR

Ar

(OC)4M

Li

(OC)4M

R';

Ar

MeOTf

C

MeO

R'

O X = O, NR M = Cr, W

Based on the reaction of chiral a-lithiated carbamates it is convenient to prepare alcohols with two contiguous stereocenters from secondary boronic esters.5 Diﬂuoromethyl phenyl sulfone is lithiated by LiHMDS at –788, and the lithio species attacks cyclic sulfates of 1,2-diols and 1,2-amino alcohols to afford a,a-diﬂuoroalkyl sulfones.6 The benzenesulfonyl group can be reductively removed (Mg, HOAc, NaOAc) or eliminated to provide 1,1-diﬂuoroalkenes with an allylic OH or NH2 group. XH

Mg/HOAc

O O X S O R

XH F F

LiHMDS PhSO2CF2Li

CHF2

R

PhSO2CHF2

R

SO2Ph XH

X = O, NH LiHMDS THF

R

F F

Ketone synthesis. The reaction of 1-chloroalkenyl p-tolyl sulfoxides with lithioacetonitrile leads to 2-amino-1-cyanocyclopentadienes, which on acid hydrolysis give 2-cyclopentenones. The method has been employed in a formal synthesis of acorone.7 Tol

NC S O

Li

CN

NH2

O

Cl

Alkynones are prepared from esters by treatment with lithioalkynes and lithium morpholinide in the presence of BF3 . OEt2 at –788. More rapid aminolysis of the esters precedes an attack of the alkynides.8 Pentamethylcyclopentadienyllithium attacks ArCOCl to give Cp COAr. On further reaction with allyldimethylaluminum, tertiary alcohols are formed. Thermolysis in toluene generates allyl aryl ketones.9 The elegant application of the reaction between an a-sulfonyllithium reagent and acylsilane to afford an enol silyl ether is described in a synthetic route to limonoids.10 Brook rearrangement following the nucleophilic addition of the organolithium protects the oxy functionality.

Organolithium reagents

TBS

305

OTBS

O + Li

O

O

SO2Ph

O H O H HO

H

H

Reaction with 1,3-dithianes. The special reactivity of 2-thiomethyl-1,3-dithianes has been exploited. The thio group is eliminated to provide 2-methylene-1,3-dithiane which is susceptible to attack by organolithium reagents. Trapping of the dimeric dithianyllithium species leads to precursors of various 1,3-diketones.11

S

S

RLi

S

S

Li

S

S

SBu

Li

S S

R

R

S

S

R'CHO

O

R'

R O

HO

R' S

S

Hg++

S R

S

Addition reactions. Organolithium reagents add to a,b-unsaturated amides. If the reagents are mixed with t-BuOK the regiochemical sense is reversed (to the a-carbon).12 Organolithium RLi and Grignard reagent R0 MgX mixtures add to thioformamides to give amines RR0 CHNR00 .2 The metal sulﬁde LiSMgX created from such a mixture is a thiolating agent, for example, for converting RCOCl to RCOSH.13 A controlled opening of a,b-epoxy ketones involves reaction with Ph(Me)2SiLi and mild hydrolysis. Attack of the silyllithium reagent on the ketone groups is followed by a Brook rearrangement and b-elimination.14 1

Schla¨ger, T., Oberdorf, C., Tewes, B., Wu¨nsch, B. S 1793 (2008). McNulty, J., Das, P. CC 1244 (2008). 3 Tang, S., Han, J., He, J., Zheng, J., He, Y., Pan, X., She, X. TL 49, 1348 (2008). 2

306

Organomagnesium reagents

4

Barluenga, J., Trabano, A.A., Perez-Sanchez, I., De la Campa, R., Florez, J., Garcia-Granda, S., Aguirre, A. CEJ 14, 5401 (2008). 5 Stymiest, J.L., Dutheuil, G., Mahmood, A., Aggarwal, V.K. ACIE 46, 7491 (2007). 6 Ni, C., Liu, J., Zhang, L., Hu, J. ACIE 46, 786 (2007). 7 Satoh, T., Kawashima, T., Takahashi, S., Sakai, K. T 59, 9599 (2003). 8 Yim, S.J., Kwon, C.H., An, D.K. TL 48, 5393 (2007). 9 Iwasaki, M., Morita, E., Uemura, M., Yorimitsu, H., Oshima, K. SL 167 (2007). 10 Behenna, D.C., Corey, E.J. JACS 130, 6720 (2008). 11 Valiulin, R.A., Halliburton, L.M., Kutateladze, A.G. OL 9, 4061 (2007). 12 Hinago, T., Teshima, N., Kenmoku, S., Kamata, T., Terauchi, N., Chiba, N., Satoh, C., Nakamura, A., Asaoka, M. CL 36, 54 (2007). 13 Murai, T., Asai, F. JACS 129, 780 (2007). 14 Reynolds, S.C., Wengryniuk, S.E., Hartel, A.M. TL 48, 6751 (2007).

Organomagnesium reagents. Deprotonation. Enolization of ketones with t-Bu2Mg and treatment of the enolates with Me3SiCl –LiCl in THF at 08 afford silyl enol ethers.1 1

Kerr, W.J., Watson, A.J.B., Hayes, D. SL 1386 (2008).

Organozinc reagents. Zincation. Sensitive arenes and heteroarenes undergo zincation using as base zinc bis(2,2,6,6-tetramethylpiperidide), [complexed with MgCl2], which is prepared from the corresponding chloromagnesium amide and ZnCl2 in THF.1 Zincation at C-2 of benzofurans, benzothiophenes, N-Boc indoles and the like (to generate the corresponding diarylzincs) is also achieved via lithiation with LiTMP and treatment with (tmeda)ZnCl2.2 Lithium dialkyl(2,2,6,6-tetramethylpiperidino)zincates are readily formed from R2Zn and lithium 2,2,6,6-tetramethylpiperidide. The alkyl group in such reagents is critical to their utility in zincation of haloarenes. Rapid elimination occurs after reaction with the dimethylzincate, but o-bromaryldi-t-butylzincates persist and they can used to react with electrophiles.3

Br

Br

Li

ZnR2

Li N ZnR2

I2 R = t-Bu

Br I

R = Me

Organozinc reagents

307

2,3-Disubstituted succinic esters.4 Substituted succinic esters differentiated at the two termini and alkyl substituents (one being an allyl group) are readily prepared from diallyl fumarate. Copper-catalyzed conjugate addition of R2Zn in the presence of Me3SiCl leads to silyl ketene acetals in which the other O-substituent is allyl. On warming, an Ireland– Claisen rearrangement occurs, furnishing succinic esters.

O

O RZn2

O

O R

O

[cat]

O

R

O

Me 3SiCl

O

O

O

[cat] =

O

O O

SiMe3

SiMe3

N O Cu N

Alkenylzinc reagents. Hydroboration of pinacolatoborylalkynes with dicyclohexylborane affords 1,1-diboryl-1-alkenes. The dicyclohexylboryl group is selectively exchanged on treatment with Me2Zn, and the resulting species show differentiated chemoselectivity such that homologation/functionalization proceed in a desired manner.5

R

B

O O

MeZn Cy2BH;

B

O O

Me2Zn

R R'CHO

R' HO B

O O

R

1-Bromo-1-dibromoborylalkenes are useful for the synthesis of trisubstituted alkenes. Reaction with R2Zn (as demonstrated by Me2Zn) affords alkenylzinc species which can be converted to the corresponding alkenyl iodides for further coupling.6 Allenylarenes undergo lithiation at a far sp 2-terminus of the diene system on exposure to LDA. Negishi coupling enables transforming the parent compounds into 1,3-diarylallenes upon conversion of the lithio derivatives to zincio species.7

308

Organozinc reagents

Ar

LDA; ZnBr 2;

C R

(Ph3P)4Pd

Ar

Ar' C R

Ar'I

Addition reactions. Allylzinc reagents add to t-butanesulﬁnylimines in a straightforward fashion.8 Interestingly, the products can be different from those using the corresponding Grignard reagents.

HN H M = MgCl

[M] N

+

O S R

O S

R

HN M = ZnC6H7

O S R

For hydroamination a co-catalyst system contains {PhNMe2H[B(C6F5)4]} and 1, which is made from Me2Zn.9 Hydrosilylation of terminal alkenes employing t-butylzinciosilanes and lithium biphenyl-2,20 -dioxide in the presence of CuCN proceeds nicely.10

C12H23 N Zn-Me N C12H23

(1) Reformatsky reagents are found to perform conjugate addition to alkylidenemalonic esters.11 Allylic substitution.12 Catalyzed by CuCl, the reaction of RZnBr (R ¼ aryl, alkenyl) with cis-4-cyclopentene-1,3-diol monoesters proceeds regioselectively along an SN20 pathway to provide trans-2-substituted 3-cyclopentenols. Homologation.13 Ethyl(iodomethyl)zinc contributes a methylene group while effectuating a debrominative dimerization of bromomethyl ketones. Formation of the reaction products involves a rearrangement step.

Organozinc reagents (1)

Ph

R

MO

Si

Si

R

CuCN

309

Ph

Zn MO (1) CuCN

Si

M = Li, MgCl 75%

(1) O

O Br

Ar

+

I

Br

+

I

O

ZnEt

Ar

Ar

O R

Ph

O

ZnEt

OH

R

R O

or

R

R

Negishi coupling.14 Differences in reactivity on using R2Zn and RZnX are due to formation of isomeric four-coordinate Pd complexes.

Me MeZnCl

ArF Pd Cl

PPh3 F

Ar

ArF—Me

PPh3

Pd Cl PPh3

PPh3 Me2Zn

F

Ar

Me2Zn

(Ph3P)2PdMe2

Pd Me PPh3

1

fast

+ ArF—ZnMe

Wunderlich, S.H., Knochel, P. ACIE 46, 7685 (2007). L’Helgonal’ch, J.-M., Seggio, A., Chevallier, F., Yonehara, M., Jeanneau, E., Uchiyama, M., Mongin, F. JOC 73, 177 (2008). 3 Uchiyama, M., Kobayashi, Y., Furuyama, T., Nakamura, S., Kajihara, Y., Miyoshi, T., Sakamoto, T., Kondo, Y., Morokuma, K. JACS 130, 472 (2008). 4 Bausch, C.C., Johnson, J.S. JOC 73, 1575 (2008). 5 Li, H., Carroll, P.J., Walsh, P.J. JACS 130, 3521 (2008). 6 Huang, Z., Negishi, E. JACS 129, 14788 (2007). 2

310

Osmium tetroxide

7

Zhao, J., Liu, Y., Ma, S. OL 10, 1521 (2008). Maji, M.S., Fro´´hlich, R., Studer, A. OL 10, 1847 (2008). 9 Dohlnahl, M., Lo¨hnwitz, K., Pissarek, J.-W., Biyikal, M., Schulz, S.R., Scho¨n, S., Meyer, N., Roesky, P.W., Blechert, S. CEJ 13, 6654 (2007). 10 Nakamura, S., Uchiyama, M. JACS 129, 28 (2007). 11 Benz, E., Moloney, M.G., Westaway, S.M. SL 733 (2007). 12 Nakata, K., Kiyotsuka, Y., Kitazume, T., Kobayashi, Y. OL 10, 1345 (2008). 13 Li, L., Cai, P., Xu, D., Guo, Q., Xue, S. JOC 72, 8131 (2007). 14 Casares, J.A., Espinet, P., Fuentes, B., Salas, G. JACS 129, 3508 (2007). 8

Osmium tetroxide. Osmylation. A review of recent works on osmylation of alkenes has been published.1 1

Francais, A., Bedel, O., Haudrechy, A. T 64, 2495 (2008).

Oxalic acid. Cleavage of dithioacetals. Use of oxalic acid in MeNO2 to regenerate carbonyl compounds represents a mild method.1 1

Miyake, H., Nakao, Y., Sasaki, M. CL 36, 104 (2007).

1-Oxo-4-acetamino-2,2,6,6-tetramethylpiperidinium tetraﬂuoroborate. Allylic oxidation. An ene-type reaction occurs when alkenes are treated with the title reagent in MeCN at room temperature.1 1

Pradhan, P.P., Bobbitt, J.M., Bailey, W.F. OL 8, 5485 (2006).

Oxygen. Dehydrogenation. 2-Arylimidazoles are formed on heating the 4,5-dihydro derivatives with activated carbon in xylene under oxygen.1 Oxidations Metal-catalyzed aerobic oxidation of organic compounds has been reviewed.2 Aerial oxidation of primary and secondary alcohols is mediated by TEMPO in the presence of HCl and NaNO2.3 Secondary benzylic alcohols undergo aerial oxidation (or with t-BuOOH) based on catalysis by AuCl – neocuproine,4 but another report describes the oxidation of both primary and secondary alcohols (to acids and ketones, respectively) using nanoclusters of gold that are stabilized by poly(N-vinyl-2-pyrrolidone).5 Allylic oxidation, for example, of cyclohexene to 2-cyclohexenone, and oxidative cleavage of styrene to benzaldehyde are readily accomplished with oxygen; such reaction systems contain N-hydroxyphthalimide and 1,4-diamino-2,3-dichloro-9,10-anthraquinone.6 Aldehydes are converted into carboxylic acids with Pd/C, KOH and catalytic amounts of NaBH4 in the air.7 Very similar conditions (K2CO3 instead of KOH) are described for oxidation of benzylic and allylic alcohols.8

Oxygen

311

Arylacetamides undergo aerial oxidation to yield the corresponding a-keto amides without the need of a transition metal salt. The transformation is carried out in the presence of a base (Cs2CO3) and Bu4NBr.9 Primary amines are converted into oximes in an aerobic oxidation employing 1,1-diphenyl-2-picrylhydrazyl (1) and WO3/Al2O3 as catalyst.10 O2N Ph2N

NO2

N O2N

(1) Perhaps of more practical value is the oxygenation of alkanes, and a reaction catalyzed by VO(acac)2 is notable.11 Oxidative coupling. N-Alkenylation of carboxamides to acquire enamides is accomplished by potassium alkenyltriﬂuoroborates. It involves treatment of the reaction components with Cu(OAc)2 under oxygen in the presence of 4A-molecular sieves.12 Certain ynamides are obtained from 1-alkynes and amine derivatives (e.g., 3-acylindoles, imidazolidinones, oxazolidinones, and sulfonamides) by coupling under oxygen, using the CuCl2-pyridine catalyst.13 Aldehydes and isonitriles undergo hydrative condensation. Depending on the hydrophilicity of the isonitriles, either a-hydroxycarboxamides or a-acyloxycarboxamides are formed.14 OH

O2

RCHO

+

CN

R'

H2O

O

O2

+

CN

R'

R'

O

(hydrophilic)

RCHO

H N

R

H2O

R

R

H N

O

(hydrophobic)

R'

O

o-Arylation of anilides15 proceeds on heating with arenes and Pd(OAc)2, DMSO, and CF3COOH under oxygen (1 atm.) at 100o. Twofold CZH activation is involved in the coupling. O +

MeO R

ArHN

O O2 Pd(OAc)2 CF3COOH–DMSO 100o

MeO

N Ar R

312

Oxygen, singlet

Dimerization of 1-alkynes is accomplished with 1% Pd/C, CuI in DMSO under oxygen at room temperature.16 This protocol is base-free and ligand-free. Homocoupling of Grignard reagents also takes place in dry air, with some MnCl2 or FeCl3 as catalyst.17,18 Oxidative cross-coupling of 2-naphthols is catalyzed by Cu(OH)Cl-TMEDA and assisted by Yb(OTf)3. Under such conditions BINOL containing a single methyl ester at C-3 is formed with .99% selectivity.19 Short chain v-alkynamides undergo Wacker oxidation and coupling with 1-alkenes in tandem, on treatment with Na2PdCl4, CuCl2 in MeCN–H2O (5 : 1) under O2.20

O R

+

O

R" O2

N R'

Na2PdCl4 –CuCl2 MeCN–H2O (5 : 1)

R

N R'

Addition reactions. Under oxygen B-propylcatecholborane Markovnikov hydrophosphorylation of 1-alkenes.21

R" O

catalyzes

anti-

1

Haneda, S., Okui, A., Ueba, C., Hayashi, M. T 63, 2414 (2007). Piera, J., Ba¨ckvall, J.-E. ACIE 47, 3506 (2008). 3 Wang, X., Liu, R., Jin, Y., Liang, X. CEJ 14, 2679 (2008). 4 Li, H., Guan, B., Wang, W., Xing, D., Fang, Z., Wan, X., Yang, L., Shi, Z. T 63, 8430 (2007). 5 Tsunoyama, H., Tsukuda, T., Sakurai, H. CL 36, 212 (2007). 6 Tong, X., Xu, J., Miao, H., Yang, G., Ma, H., Zhang, Q. T 63, 7634 (2007). 7 Lim, M., Yoon, C.M., An, G., Rhee, H. TL 48, 3835 (2007). 8 An, G., Lim, M., Chun, K.-S., Rhee, H. SL 95 (2007). 9 Song, B., Wang, S., Sun, C., Deng, H., Xu, B. TL 48, 8982 (2007). 10 Suzuki, K., Watanabe, T., Murahashi, S.-I. ACIE 47, 2079 (2008). 11 Kobayashi, H., Yamanaka, I. CL 36, 114 (2007). 12 Bolshan, Y., Batey, R.A. ACIE 47, 2109 (2008). 13 Hamada, T., Ye, X., Stahl, S.S. JACS 130, 833 (2008). 14 Shapiro, N., Vigalok, A. ACIE 47, 2849 (2008). 15 Brasche, G., Garcia-Fortanet, J., Buchwald, S.L. OL 10, 2207 (2008). 16 Kurita, T., Abe, M., Maegawa, T., Monguchi, Y., Sajiki, H. SL 2521 (2007). 17 Cahiez, G., Moyeux, A., Buendia, J., Duplais, C. JACS 129, 13788 (2007). 18 Liu, W., Lei, A. TL 49, 610 (2008). 19 Yan, P., Sugiyama, Y., Takahashi, Y., Kinemuchi, H., Temma, T., Habaue, S. T 64, 4325 (2008). 20 Momiyama, N., Kanan, M.W., Liu, D.R. JACS 129, 2230 (2007). 21 Montgomery, I., Parsons, A.F., Ghelﬁ, F., Roncaglia, F. TL 49, 628 (2008). 2

Oxygen, singlet. Oxygenation. Photooxidation of primary alcohols to RCOOH and ArMe to ArCOOH is accomplished in EtOAc, in the presence of Ph3P and CBr4.1 The light source of the reaction is a ﬂuorescent lamp.

Ozone

313

A new electron-transfer mediator for photooxygenation of alkenes (to give allylic hydroperoxides) and methylarenes (to give aromatic aldehydes) is 9-mesityl-10-methylacridinium perchlorate (1).2

O2 hν (1)

OOH

N

CHO

O2 hν

ClO4

(1)

(1 ) N-Benzyl carboxamides undergo photooxidation to deliver aroylimides, which is catalyzed by iodine.3 2-Allyl-5-silylfurans are converted into spiroperoxy lactones on treatment with singlet oxygen and then an acid.4 O

SiMe3

O

O

O hν O2; TsOH

O O

O +

O O

Degradation. a-Substituted mandelic acids are oxidatively degraded to aryl ketones by singlet oxygen in the presence of iodine. Unsubstituted analogs give aroic acids.5 Actually, many alkylarenes are converted into aroic acids by singlet oxygen using allyl bromide as catalyst, except those carrying nitro group(s) in the aromatic nucleus.6 1

Sugai, T., Itoh, A. TL 48, 9096 (2007). Griesbeck, A.G., Cho, M. OL 9, 611 (2007). 3 Nakayama, H., Itoh, A. SL 675 (2008). 4 Margaros, I., Montagnon, T., Vassilikogiannakis, G. OL 9, 5585 (2007). 5 Nakayama, H., Itoh, A. TL 49, 2792 (2008). 6 Sugai, T., Itoh, A. TL 48, 2931 (2007). 2

Ozone. Cleavage of alkenes.1 Ozonization of alkenes in aqueous acetone (H2O : Me2CO ¼ 5 : 95) at 0o gives carbonyl products directly, additional reagents for decomposition of ozonides are not needed.

314

Ozone

Unsaturated organotriﬂuoroborate salts are cleaved at the CC multiple bond to yield carbonyl compounds. The triﬂuoroborate group is resistant to attack by ozone.2 Ozonolysis of 1-triorganosilyl-1-alken-3-ols afford a-formyl-b-hydroxy silyl peroxides.3 OH O3

OH R

1

SiR'3

Schiaffo, C.E., Dussault, P.H. JOC 73, 4688 (2008). Molander, G.A., Cooper, D.J. JOC 72, 3558 (2007). 3 Igawa, K., Sakita, K., Murakami, M., Tomooka, K. S 1641 (2008). 2

CHO

R

EtOAc –78°

O

OSiR'3

P Palladacycles. Coupling. In the synthesis of ArCHvCH2 and ArCHvCHAr 0 from ethylene by the Heck-reaction both steps can be catalyzed by palladacycle 1.1

O Pd P O Ar Ar

Ar Ar O P Pd O

ArX

Ar'

Ar'X

Ar

(1)

(1)

Ar

(1) Ar = o -Tol Pincer complexes 2 are active catalysts for the Heck reaction. Interestingly, their catalytic activities are controlled by the central metal atom of the porphyrin nucleus.2

Ar

N

N M

Ar N

N

N Pd Cl N

O O P O Pd Cl 2

Ar

(2) M = Zn > Ni > Cu > H, H

(3)

In a preparation of ArCN from ArX and K4Fe(CN)6, the employment of a palladacycle3 as a catalyst under rather drastic conditions (NMP, 140o) is perhaps of questionable value. Coupling reactions catalyzed by Pd complexes of the Se-C-Se pincer type are accelerated when the p-position to the metal atom is substituted by an electron donor (e.g., MeO group).4 Allylation. In the addition of allylstannanes to aldehydes and N-tosylimines, 3 and 4 act in the promoter role, respectively.5,6 Noteworthy is that the pincer complex 4 features two different but synergistic donor groups. Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 315

316

Palladium

R Ph2P

Pd

MeCN

Cl

SPh (4)

BF4

(4)

R

Me6Sn2

SnMe3

ArCH=NTs

R Ar

NHTs

The S,S-pincer 5, cocatalyzed by TsOH, converts allylic alcohols to allylboronic acids for direct allylation of aldehydes.7

R

MeS

Pd

MeCN

(5)

(5)

SMe BF4

OH

[B(OH)2]2

TsOH

R R

B(OH)2

R'CHO

R'

OH

1

Kormos, C.M., Leadbeater, N.E. JOC 73, 3854 (2008). Katoh, T., Shinokubo, H., Osuka, A. JACS 129, 6392 (2007). 3 Cheng, Y., Duan, Z., Li, T., Wu, Y. SL 543 (2007). 4 Aydin, J., Selander, N., Szabo, K.J. TL 47, 8999 (2006). 5 Bedford, R.B., Pilarski, L.T. TL 49, 4216 (2008). 6 Gagliardo, M., Selander, N., Mehendale, N.C., van Koten, G., Gebbink, R.J.M.K., Szabo, K.J. CEJ 14, 4800 (2008). 7 Selander, N., Kipke, A., Sebelius, S., Szabo, K.J. JACS 129, 13723 (2007). 2

Palladium. Hydrogenation. The polyethyleneimine complex of Pd is useful for partial hydrogenation of alkynes.1 Selective reduction of alkenes under transfer hydrogenation conditions (hydrogen source: HCOOH) is accomplished with Pd and t-Bu3P.2 Numerous substrates including styrene, stilbene, allylic alcohols, enals, enones, enoic acids, conjugated nitriles are susceptible to reduction, although the pinenes do not react. A recyclable system of Pd nanoparticulates in water for hydrogenation of alkenes such as conjugated carbonyl compounds, esters, nitriles, allylic alcohols and ethers, styrenes, has been developed.3 Coupling reactions. Pd nanoparticles supported on polyaniline ﬁbers are catalytically active for Suzuki coupling. 2-Chlorobiaryls are obtainable from a reaction of ArB(OH)2 with 1,2-dichlorobenzene.4 The products can be used to prepare 2-hydroxybiaryls. There are

Palladium/carbon

317

many other types of Pd nanoparticles on solid supports, the one version (from reduction of Na2PdCl4 with hydrazine) deposited on NiFe2O4, proved active in Heck and Suzuki coupling, has the advantage of magnetic recovery.5 It is possible to synthesize diarylamines or triarylamines from ArBr by reaction with BnONH2. The catalyst system contains Pd, t-Bu3P, and t-BuONa.6 1

Sajiki, H., Mori, S., Ohkubo, T., Ikawa, T., Kume, A., Maegawa, T., Monguchi, Y. CEJ 14, 5109 (2008). 2 Brunel, J.M. T 63, 3899 (2007). 3 Callis, N.M., Thiery, E., Le Bras, J., Muzart, J. TL 48, 8128 (2007). 4 Gallon, B.J., Kojima, R.W., Kaner, R.B., Diaconescu, P.L. ACIE 46, 7251 (2007). 5 Baruwati, B., Guin, D., Manorama, S.V. OL 9, 5377 (2007). 6 Bedford, R.B., Betham, M. TL 48, 8947 (2007).

Palladium/alumina. Suzuki coupling.1 The catalyst is prepared from impregnating Pd(OAc)2 in alumina and calcined. With KF in EtOH, Suzuki coupling is conducted. 1

Kudo, D., Masui, Y., Onaka, M. CL 36, 918 (2007).

Palladium/calcium carbonate. Stille coupling.1 With this catalyst reservoir the Stille coupling is performed with ligand-free Pd in aq. EtOH. 1

Coelho, A.V., de Souza, A.L.F., de Lima, P.G., Wardell, J.L., Antunes, O.A.C. TL 48, 7671 (2007).

Palladium/carbon. Deprotection. Aryl ketones are recovered from 2-aryl-1,3-dithianes on heating with Pd/C and the resin Amberlite IR-120 in MeOH.1 The presence of the aryl group is critical. Hydrogenation. Transfer hydrogenation (Pd/C, HCOONH4) affects alkenylfurans and benzyloxy substituents. Enones are reduced to saturated alcohols.2 OBn

O CH

BnO

OH

Pd/C, HCOONH 4

O

MeOH–THF (2 : 1)

HO

The formyl group of activated aromatic aldehydes such as p-anisaldehyde is deoxygenated on hydrogenation. The hydrogenolysis is promoted by HCl.3 From nitroarenes hydrogenation in the presence of aldehydes leads to N-monoalkyl arylamines.4 Hydrogenation of 2-(o-nitroaryl)-2-cycloalkenones gives annulated indoles (e.g., tetrahydrocarbazoles).5

318

Palladium(II) acetate

Pd/C, H2

O NO2

N H

Reduction with nascent hydrogen generated from Et3SiH has been reported.6 Coupling reactions. Studies of coupling reactions that are catalyzed by Pd/C continue. Ligand-free Pd-catalyzed Suzuki coupling is an obvious advantage, and Pd/C is a reusable catalyst showing no leaching of the metal into solution (i.e., ,1 ppm).7,8 Another report regarding Suzuki coupling with ArCl with assistance of a X-Phos ligand.9 In the aerogel form, Pd/C is also capable of catalyzing the Sonogashira coupling.10 N,N-Dimethylbenzamides are obtained from ArI, DMF on heating with Pd/C and POCl3 at 1408.11 For transformation of ArBr into ArCN in NMP, the cyanide source is K4Fe(CN)6 and a catalyst-additive system is made from Pd/C (1 mol%), Na2CO3, and Bu3N.12 1

Wang, E.-C., Wu, C.-H., Chien, S.-C., Chiang, W.-C., Kuo, Y.-H. TL 48, 7706 (2007). Nandy, S.K., Liu, J., Padmapriya, A.A. TL 48, 2469 (2007). 3 Xing, L., Wang, X., Cheng, C., Zhu, R., Liu, B., Hu, Y. T 63, 9382 (2007). 4 Sydnes, M.O., Isobe, M. TL 49, 1199 (2008). 5 Scott, T.L., Burke, N., Carrero-Martı´nez, G., So¨derberg, B.C.G. T 63, 1183 (2007). 6 Mandal, P.K., McMurray, J.S. JOC 72, 6599 (2007). 7 Maegawa, T., Kitamura, Y., Sako, S., Udzu, T., Sakurai, A., Tanaka, A., Kobayashi, Y., Endo, K., Bora, U., Kurita, T., Kozaki, A., Monguchi, Y., Sajiki, H. CEJ 13, 5937 (2007). 8 Kitamura, Y., Sakurai, A., Udzu, T., Maegawa, T., Monguchi, Y., Sajiki, H. T 63, 10596 (2007). 9 Simeone, J.P., Sowa Jr, J.R. T 63, 12646 (2007). 10 Soler, R., Cacchi, S., Fabrizi, G., Forte, G., Martin, L., Martinez, S., Molins, E., Moreno-Manas, M., Petrucci, F., Roig, A., Sebastian, R.M., Vallribera, A. S 3068 (2007). 11 Tambade, P.J., Patil, Y.P., Bhanushali, M.J., Bhanage, B.M. TL 49, 2221 (2008). 12 Zhu, Y.-Z., Cai, C. EJOC 2401 (2007). 2

Palladium(II) acetate. Coupling reactions. Various coupling reactions involving nonpolar substrates may be carried out with hydrophobicized silica sol-gel matrix in which Pd(OAc)2 is trapped. The substrates form microemulsions in water with SDS and ROH. The catalyst is leach-proof and reusable.1 Heck reaction with ArB(OH)2 is achieved in the air under mild conditions when 2,9dimethyl-1,10-phenanthroline is present.2 A carboxylate ion directs palladation of a CZH bond for coupling with organoboronates, and the reaction is useful for attaching a carbon fragment to an o-position of aroic acids and homologation at the methyl group of t-alkanoic acids.3 Suzuki coupling catalyzed by Pd(OAc)2 and assisted by (Me2N)2CvNBu is very efﬁcient. In aqueous solvent at room temperature a typical reaction of PhB(OH)2 and 4-O2NC6H4I shows TON of up to 850,000.4 Also reported are methods employing cryptand-22,5 N-phenylurea,6 and a polymer N-linked to DABCO.7

Palladium(II) acetate

319

A ligand-free Suzuki coupling protocol indicates employment of Pd(OAc)2 in PEG-400, in which nanoparticles of Pd are generated in situ.8 More conventionally, NaOMe is used as a base for coupling at room temperature.9 Under certain coupling reaction conditions reduction of nitro group(s) also occurs.10 Pd(OAc)2

X NO2

+

Ar

K2CO3

ArB(OH)2

DMF–H2O (5:1)

NH2

150o

Under oxygen and in the presence of Pd(OAc)2 organoboronic acids/esters couple with electron-deﬁcient alkenes, no base is needed.11 A conjugated polyene chain can be assembled stereoselectively by iterative Suzuki coupling. The strategy is based on using a chelated boronato group to moderate reactivity.12

Me N O O

O B O

Br +

Me N Pd(OAc)2 KF PhMe, 25o

(HO)2B

O O

R

O B O R = Pr

R

(HO)2B

R

96%

Indoles are synthesized from o-iodoaroic acids, via Curtius rearrangement and subsequent coupling reactions of the aryl isocyanates.13

Ph I N

OBn

Pd(OAc)2

C

O

SiMe3

base DMF 120o

coupling partner:

N H

N H Ph

SiMe3

OHC

OBn

There is no need to protect the NZH of indoles and pyrroles during coupling (at C-2) with ArI, while employing Pd(OAc)2 as catalyst and a mild base of CsOAc in DMA at 1258.14 A rather unusual catalyst system for Heck and Suzuki couplings constitutes a salen complex that is formed by adding Pd(OAc)2 to the ligand,15 and for Heck reaction in water, sodium 2-[(pyrid-3-yl)ethyl]aminoethanesulfonate serves as a base and ligand.16 Intramolecular coupling involving a Fischer carbene unit is particularly interesting. While both quinoline and indole derivatives are produced in the reaction, it is arrested upon change of the catalyst to Pd(MeCN)2Cl2.17

320

Palladium(II) acetate

OEt I

Pd(OAc)2

Ph

N H EtO

Ph +

DMF

N

COOEt N H

Ph

Cr(CO)5

I (MeCN)2Pd(OAc)2

N N Pd

Ph

MeCN

I

Ph

EtO OEt

In the formation of indoles from o-haloarylamines and alkynes, regioselectivity is attained to some degrees. The larger substituent of the alkyne appears at C-2 of the product.18 Rs

Rs

I

Pd(OAc)2

+ NHR

RL

RL

PhNHCONH2 DMF 130o

N H

When ArBr, an alkyne, and K4Fe(CN)6 are heated with Pd(OAc)2 in DMA, cis-arylcyanation of the alkyne occurs. Substituted (Z )-cinnamonitriles are obtained in moderate to good yields.19 R ArBr

Pd(OAc)2

+ R

K4Fe(CN)6 AcNMe2120o

R

Ar

R

CN

Air-stable hexaarylcyclotrisiloxanes, which are generated from Ar2Si(OH)2 on contact with TsOH, are activated by KOH to undergo cross-coupling with ArX.20 Hydrosilanes can be used to couple with electron-deﬁcient ArI at room temperature. Additives to complement Pd(OAc)2 are LiCl and pyridine.21 cis-Hydroarylation by ArN2BF4 and Ph3SiH proceeds at room temperature.22 A rather unusual ligand is the ruthenocene 1 that is used in Heck reaction catalyzed by Pd(OAc)2.23 N N R

Ru R

P

(1) In the Pd-catalyzed arylation of unactivated arenes such as benzene with ArBr, pivalic acid is a key cocatalyst.24

Palladium(II) acetate

321

Cyclization. Two different modes of cyclization are available to 2,2-diﬂuoro-3alkynamides. The 4-exo-dig mode is favored by the Pd-catalysis, while 5-endo-dig cyclization occurs in the presence of TBAF.25 F Pd(OAc)2

F

CONHR

F

O

F

NR R' F

R'

Bu4NF

O

F NR R'

Halogenation.26 Aroic acids undergo o-iodination by IOAc in the presence of Pd(OAc)2. Thus 2,6-diiodobenzoic acid is produced. However, if R4NX (X ¼ Br, I) is added the anion is rapidly oxidized and it becomes the electrophile. 1

Tsvelikhovsky, D., Blum, J. EJOC 2417 (2008). Lindh, J., Enquist, P.-A., Pilotti, A., Nilsson, P., Larhed, M. JOC 72, 7957 (2007). 3 Giri, R., Maugel, N., Li, J.-J., Wang, D.-H., Breazzano, S.P., Saunders, L.B., Yu, J.-Q. JACS 129, 3510 (2007). 4 Li, S., Lin, Y., Cao, J., Zhang, S. JOC 72, 4067 (2007). 5 Hsu, M.-H., Hsu, C.-M., Wang, J.-C., Sun, C.-H. T 64, 4268 (2008). 6 Cui, X., Zhou, Y., Wang, N., Liu, L., Guo, Q.-X. TL 48, 163 (2007). 7 Li, J.-H., Hu, X.-C., Xie, Y.-X. TL 47, 9239 (2006). 8 Han, W., Liu, C., Jin, Z.-L. OL 9, 4005 (2007). 9 Deng, C.-L., Guo, S.-M., Xie, Y.-X., Li, J.-H. EJOC 1457 (2007). 10 Wang, H.-S., Wang, Y.-C., Pan, Y.-M., Zhao, S.-L., Chen, Z.-F. TL 49, 2634 (2008). 11 Yoo, K.S., Yoon, C.H., Jung, K.W. JACS 128, 16384 (2006). 12 Lee, S.J., Gray, K.C., Paek, J.S., Burks, M.D. JACS 130, 466 (2008). 13 Leogane, O., Lebel, H. ACIE 47, 350 (2008). 14 Wang, X., Gribkov, D.V., Sames, D. JOC 72, 1476 (2007). 15 Borhade, S.R., Waghmode, S.B. TL 49, 3423 (2008). 16 Pawar, S.S., Dekhane, D.V., Shingare, M.S., Thore, S.N. TL 49, 4252 (2008). 17 Lopez-Alberca, M.P., Mancheno, M.J., Fernandez, I., Gomez-Gallego, M., Sierra, M.A., Torrs, R. OL 9, 1757 (2007). 18 Cui, X., Li, J., Fu, Y., Liu, L., Guo, Q.-X. TL 49, 3458 (2008). 19 Cheng, Y., Duan, Z., Yu, L., Li, Z., Zhu, Y., Wu, Y. OL 10, 901 (2008). 20 Endo, M., Sakurai, T., Ojima, S., Katayama, T., Unno, M., Matsumoto, H., Kowase, S., Sano, H., Kosugi, M., Fugami, K. SL 749 (2007). 21 Iizuka, M., Kondo, Y. EJOC 1161 (2008). 22 Cacchi, S., Fabrizi, G., Goggiamani, A., Persiani, D. OL 10, 1597 (2008). 23 Yorke, J., Wan, L., Xia, A., Zhang, W. TL 48, 8843 (2007). 24 Lafrance, M., Fagnou, K. JACS 128, 16496 (2006). 25 Fustero, S., Fernandez, B., Bello, P., del Pozo, C., Arimitsu, S., Hammond, G.B. OL 9, 4251 (2007). 26 Mei, T.-S., Giri, R., Maugel, N., Yu, J.-Q. ACIE, 47, 5215 (2008). 2

322

Palladium(II) acetate – imidazol-2-ylidene

Palladium(II) acetate – imidazol-2-ylidene. Coupling reactions. Using complexes in which Pd is coordinated with polymersupported azolecarbene ligands Suzuki coupling between ArB(OH)2 and Ar 0 N2BF4 or haloarenes has been studied.1,2 A ligand (1) containing three carbene units has been prepared and used in conjunction with Pd(OAc)2 in the Heck reaction.3 R N N

N N

RN

NR

(1) Aryl ketones and esters. A Pd-carbene complex is useful for synthesis of heteroaryl ketones under CO.4 The coupling involving ArCHO in the air leads to aryl aroates.5

N +

Cl ArB(OH)2

Pd(OAc)2 dioxane 140o

Cs2CO3 MesN

air, PhMe 120o

+

O

Cl NMes

Pd(OAc)2

ArCHO

Ar

N

ArCOOAr'

Ar'B(OH)2 CsF

MesN

NMes

BF4 1

Qin, Y., Wei, W., Luo, M. SL 2410 (2007). Lee, D.-H., Kim, J.-H., Jun, B.-H., Kang, H., Park, J., Lee, Y.-S. OL 10, 1609 (2008). 3 o¨zdemir, I., Demir, S., Centinkaya, B. SL 889 (2007). 4 Maerten, E., Sauthier, M., Mortreux, A., Castanet, Y. T 63, 682 (2007). 5 Qin, C., Wu, H., Chen, J., Liu, M., Cheng, J., Su, W., Ding, J. OL 10, 1537 (2008). 2

Palladium(II) acetate – copper salts. Cyclization. Intramolecular addition of a guanidino group to a double bond is promoted by Pd(OAc)2 (10 mol%) and Cu(OAc)2 (2.1 equiv.). Bicyclic products containing a bridgehead nitrogen atom are usually obtained in good yields.1 H N

NHCOOR NCOOR

NCOOR Pd(OAc)2 – CuCl2 K2CO3

DMFv

N

NCOOR

Palladium(II) acetate – copper salts

323

Coupling reactions. a-Arylation of cyclic enaminones (vinylogous lactams) is accomplished by coupling with ArBF3K, but N-Boc derivatives fail to follow suit.2 A carboxyl group in the ﬁve-membered ring of benzannulated heteroles plays an o-directing role and its is detached at the end of the coupling reaction.3 COOR +

COOR Pd(OAc)2–Cu(OAc)2

COOH

LiOAc, 4A-MS, AcNMe2

Z

Z

Z = O, S, NR' COOH +

COOR

N R'

COOR

Pd(OAc)2–Cu(OAc)2 LiOAc, 4A-MS, AcNMe2

N R'

N-Acylindoles are arylated at either C-3 or C-2, by changing the auxiliary metal salt, i.e., from Cu(OAc)2 to AgOAc.4 Such phenomenon had been reported in the previous year using catalyst systems based on Pd(OCOCF3)2. [loc. cit.] N-Acylated indolines and 1,2,3,4-tetrahydroquinolines free of o-substituent to the heteroatom are arylated by reaction with ArB(OH)2. Besides Pd(OAc)2, the catalyst system also contains equivalents of Cu(OTf)2 and Ag2O.5 Similarly, a protocol for the Pd-catalyzed o-arylation of acetanilides employs Cu(OTf)2 and AgF, with ArSi(OR)3 as aryl group donors.6 Further variants of coupling conditions involving oxygen in a carboxylic acid solvent enable the use of ArH as reaction partners.7,8 Cyclization of N-aroylindoles proceeds via double CZH activation.9 Pd(OAc)2

Ph N Ac

AgOAc / dioxane 120o

+ PhH N Ac

Ph Pd(OAc)2

N Ac

Cu(OAc)2 / dioxane 120o

Pd(OAc)2

+ PhH O

CuOAc / HOAc H4PMo11VOm O2

Ph O

Pd(OAc)2

N

CuOAc / HOAc H4PMo11VOm O2

O OMe

N OMe O 82%

324

Palladium(II) acetate – oxidants

Oxidative amination carried out under improved catalyst reoxidation conditions permits the use of alkenes as limiting reagents.10

O2, Pd(OAc)

2

+

R

O

N H

O

Cu(OAc)2 / PhCN

O

N

60o COOMe

O

R

1

Ho¨velmann, C.H., Streuff, J., Brelot, L., Muniz, K. CC 2334 (2008). Ge, H., Niphakis, M.J., Georg, G.I. JACS 130, 3708 (2008). 3 Maehara, A., Tsurugi, H., Satoh, T., Miura, M. OL 10, 1159 (2008). 4 Potavathri, S., Dumas, A.S., Dwight, T.A., Naumiec, G.R., Hammann, J.M., DeBoef, B. TL 49, 4050 (2008). 5 Shi, Z., Li, B., Wan, X., Cheng, J., Fang, Z., Cao, B., Qin, C., Wang, Y. ACIE 46, 5554 (2007). 6 Yang, S., Li, B., Wan, X., Shi, Z. JACS 129, 6066 (2007). 7 Li, B.-J., Tian, S.-L., Fang, Z., Shi, Z.-J. ACIE 47, 1115 (2008). 8 Yang, S.-D., Sun, C.-L., Fang, Z., Li, B.-J., Li, Y.-Z., Shi, Z.-J. ACIE 47, 1473 (2008). 9 Dwight, T.A., Rue, N.R., Charyk, D., Josselyn, R., DeBoef, B. OL 9, 3137 (2007). 10 Rogers, M.M., Kotov, V., Chatwichien, J., Stahl, S.S. OL 9, 4331 (2007). 2

Palladium(II) acetate – oxidants. Oxidative cleavage. Alkynes are cleaved to provide two ester fragments on reaction with Pd(OAc)2, ZnCl2 . 2H2O under O2 in an alcohol at 100o.1 Aerobic oxidation of a-aminoarylacetamides leads to aroylformamides.2

Ar' Ar

N

R' CONHR

O

O2, Pd(OAc)2 K2CO3 DMF 110o

Ar

CONHR

Allylic amination. 1-Alkenes can be functionalized with double bond migration that results in derivatives of 1-amino-2-alkenes, when they are treated with TsNHCOOR and catalytic amounts of Pd(OAc)2 under O2. Maleic anhydride, 4A-molecular sieves and NaOAc are the proper additives for this reaction.3 Alternatively, the same transformation is accomplished with benzoquinone as the oxidant, together with 1,2-bis(benzenesulﬁnyl)ethane and (salen)CrIIICl.4 A heterobimetallic catalytic system is involved. However, only the Pd(II) catalyst is needed for oxidative cyclization of homoallylic N-tosylcarbamates.5

Palladium(II) acetate – oxidants

COOR' N Ts H

+

O2, Pd(OAc)2

R

NaOAc AcNMe2

Ts

COOR' N

325

R

35o

Cyclization of alkenylamines usually proceeds via cis-aminopalladation.6

O

O O

Pd(OAc)2

NHTs

R

O

quinone,

SOPh

THF

SOPh

NTs

R

Functionalization at sp-carbons. Several different oxidants have been employed in oxidative functionalization. For o-acetoxylation of acylaminoarenes K2S2O8 is the oxidant,7 and oxone is present to facilitate the transfer of an ethoxycarbonyl group from DEAD to organopalladium intermediates.8

HNTs D

H Ts N

Pd(OAc)2

D

NaOAc / DMSO O2,

80o

H

Pd(OAc)2 K2S2O8 / DEAD

N

N EtOOC

ClCH2CH2Cl, 100o

85% MeO

Pd(OAc)2

NOMe

MeO

NOMe

K2S2O8 / DEAD ClCH2CH2Cl, 100

o

COOEt 72%

One of the silyl groups in N-bis(trimethylsilyl)methylcarboxamides is activated by coordination to the carbonyl and under the Heck reaction conditions it can submit a methyl group.9 Among N-directed reactions methyl group transfer from dicumyl peroxide, involving Pd insertion into the OZO bond and elimination of acetophenone to afford the transfer reagent, is also a relatively new discovery.10

326

Palladium(II) acetate – oxidants

H N

PhNH

SiMe3

O

Pd(OAc)2

+

SiMe3

benzoquinone

X

X

HOAc 20o

activated X = Ar, COOR, SO2Ph, PO(OMe)2 O

O

Pd(OAc)2

N

Ph

O O

N

Ph

130o

76% NHAc

NHAc

42%

Intramolecular oxidative addition to the double bond of o,o 0 -bifunctional stilbenes is accomplished using PhI(OAc)2 as the oxidant. This method is applicable to forming head-to-tail fused biindolines and furoindolines.11 NHTs

NTs

Pd(OAc)2 – PhI(OAc)2 Me4NCl, NaOAc DMF 23o

X

HX X = O, NTs

Allyl 2-alkynoates and amides undergo formal hydration and cycloaddition under similar conditions.12,13 The net result is equivalent to transforming the triple bond into an acylcarbenoid. R

R

IV Pd(OAc)2

[Pd]

R OAc

H

O

PhI(OAc)2

X

O

HOAc

X

O

X = O, NTs 1

Wang, A., Jiang, H. JACS 130, 5030 (2008). El Kaim, L., Gamez-Montano, R., Grimaud, L., Ibarra-Rivera, T. CC 1350 (2008).

2

X

O

Palladium(II) acetate – phase-transfer catalyst

327

3

Liu, G., Yin, G., Wu, L. ACIE 47, 4733 (2008). Reed, S.A., White, M.C. JACS 130, 3316 (2008). 5 Fraunhoffer, K.J., White, M.C. JACS 129, 7274 (2007). 6 Liu, G., Stahl, S.S. JACS 129, 63294 (2007). 7 Wang, G.-W., Yuan, T.-T., Wu, X.-L. JOC 73, 4717 (2008). 8 Yu, W.-Y., Sit, W.N., Lai, K.-M., Zhou, Z., Chan, A.S.C. JACS 130, 3304 (2008). 9 Rauf, W., Brown, J.M. ACIE 47, 4228 (2008). 10 Zhang, Y., Feng, J., Li, C.-J. JACS 130, 2900 (2008). 11 Muniz, K. JACS 129, 14542 (2007). 12 Tong, X., Beller, M., Tse, M.K. JACS 129, 4906 (2007). 13 Welbes, L.L., Lyons, T.W., Cychosz, K.A., Sanford, M.S. JACS 129, 5836 (2007). 4

Palladium(II) acetate – phase-transfer catalyst. Coupling reactions. Structural limitation of the Baylis–Hillman reaction is amended by the Heck reaction.1 OH

OH COOMe

R

Pd(OAc)2

+ ArI

Bu4NBr, KOAc MeCN

R

COOMe CHAr

Elaboration of a Baylis –Hillman adduct to give a benzoazepino[2,1-a]isoindole2 serves to demonstrate the power of the coupling method. COOMe COOMe O Br

Pd(OAc)2

N O

Bu4NBr, NaHCO 3

N

DMF 80o

55%

A convenient preparation of indene-1,1-dicarboxylic esters involves coupling of o-iodoarylmalonic esters with alkynes. The sp-carbon bearing the larger group becomes C-2, and that bearing the smaller group, C-3.3 COOEt

I

EtOOC

RL

COOEt

Pd(OAc)2

+

COOEt RL

Bu4NBr, KOAc

RS

DMF 80o

RS

RL = Ph, t-Bu, SiMe3

Electrooxidation. A mixture of Pd(OAc)2 and Bu4NX is electrooxidized in MeCN to provide (MeCN)4PdX2 for use in Wacker oxidation.4

328

Palladium(II) acetate – silver salts

1

Kim, J.M., Kim, K.H., Kim, T.H., Kim, J.N. TL 49, 3248 (2008). Gowrisankar, S., Lee, H.S., Lee, K.Y., Lee, J.-E., Kim, J.N. TL 48, 8619 (2007). 3 Zhang, D., Liu, Z., Yum, E.K., Larock, R.C. JOC 72, 251 (2007). 4 Mitsudo, K., Kaide, T., Nakamoto, E., Yoshida, K., Tanaka, H. JACS 129, 2246 (2007). 2

Palladium(II) acetate – silver salts. Coupling reactions. A catalyst system for coupling of indoles (at C-2) with ArI is made up of Pd(OAc)2, Ag2O and the ArCOOH additive, no phosphine ligand is needed.1 Cinnamyl esters are synthesized from ArI and allylic esters by the Heck reaction, the traditional leaving group (acyloxy) is retained.2 OAc

R' ArI +

R'

Pd(OAc)2 –Ag 2CO3

Ar

OAc

air, PhH

R

R

N-Methoxy-2,2-dimethylalkanamides are homologated at one of the methyl groups on reaction with organoboronic acids. The solvent of choice for arylation is t-BuOH, and for alkylation, 2,2,5,5-tetramethyltetrahydrofuran.3

R

R'

Pd(OAc)2 –Ag 2O

CONHOMe

benzoquinone, K2CO3

+ R'B(OH)2

R

CONHOMe

When neopentylpalladium intermediates are generated under non-nucleophilic conditions CZH activation is the course they pursue.4 H

Br Pd(OAc)2 Ph3P Ag2CO3

[Pd]

Bu4NBr

40%

Benzylamines are o-arylated in CF3COOH when catalyzed by Pd(OAc)2 – AgOAc.5 1

Lebrasseur, N., Larrosa, I. JACS 130, 2926 (2008). Pan, D., Chen, A., Su, Y., Zhou, W., Li, S., Jia, W., Xiao, J., Liu, Q., Zhang, L., Jiao, N. ACIE 47, 4729 (2008). 3 Wang, D.-H., Wasa, M., Giri, R., Yu, J.-Q. JACS 130, 7190 (2008). 4 Liron, F., Knochel, P. TL 48, 4943 (2007). 5 Lazareva, A., Daugulis, O. OL 8, 5211 (2006). 2

Palladium(II) acetate – tertiary phosphine. Coupling reactions. Using ligand 1 in Pd(OAc)2-catalyzed CZN bond coupling at room temperature the scope encompasses RX (R ¼ aryl, alkenyl) containing base-sensitive

Palladium(II) acetate – tertiary phosphine

329

groups.1 The catalyst system is actually an extension from a success in Suzuki coupling.2 In preparing pinacolatoborylarenes from ArCl and bis(pinacolato)diboron the biarylphosphine ligand 2 in the Pd-catalyzed reaction plays a special role; with it PdL species is favored over PdL2 and the oxidative addition to ArCl is facilitated.3 NR'2 N R

P

N

MeO

R N

N

R Cy2P MeO

N

(1)

(2)

Ligand 2 has also been employed to advantage in the coupling reaction of b,b-dihalo-oaminostyrenes leading to 2-substituted indoles.4 (With addition of Cu(OAc)2 to promote N-arylation the process runs better.) X NH2

X

Pd(OAc)2

+ ArB(OH)2

MeO

Ar N H

Cy2P MeO

A report describes an application of ferrocenylphosphine ligand 3 to Suzuki coupling involving ArCl.5 A great number of a-acetaminostyrenes are readily prepared by Heck reaction in which high regioselectivity is observed with Pd(OAc)2, DPPP, Et3N, and i-Pr2NH2BF4 in isopropanol.6 Other styrenes bearing electron-rich substituents at the a-position are similarly accessed (the superiority of alcohol solvents for the reaction is noted).7 OMe N

Fe

N Me PPh2

N N

OMe

(3) Sonogashira coupling is promoted by Pd(OAc)2, Ph3P in reﬂuxing THF, where Cp Li adequately serves as a base.8 Tertiary homoallylic alcohols undergo CC bond scission during Heck reaction.9,10 The emerging carbonyl fragment is lost from the alicyclic substrates except in the case of a 1-substituted 3-cycloalkenol.

330

Palladium(II) acetate – tertiary phosphine

R

Pd(OAc)2–Cy3P

R'

+ ArX

HO

Cs2CO3 PhMe, DMF

HO

Ar W

O + ArX Ar

Me3Si

Pd(OAc)2–Ar3P

+ ArBr HO

SiMe3

Ar

Cs2CO3 / PhMe

R

R

Cleavage of a cyclobutanol subunit also creates a site for CC coupling,11 ring strain is the cause for such reactivity.

HO

O

R Pd(OAc)2–Ph3P Cs2CO3

H

PhMe, 90o

O Br

H

OR'

Hydronaphthacenes12 and benzoﬂuorenes13 can be elaborated in one step, based on sequential allylic substitution and Heck reaction.

OAc OMe MeO

OMe E

I

MeO

OMe Pd(OAc)2–DPPE

MeO

NaH / DMF

MeO

OMe

E

O

O

65% COOEt

Pd(OAc)2–Ph3P

+

X

EtOOC

X R

CuI, Et3N DMF 60o

R' R

R'

OCOR' R = Ph, X = COOEt 81%

Palladium(II) acetate – tertiary phosphine

331

Diarylamines and o-dihaloarenes condense to give N-arylcarbazoles.14 Exposure of o-bromobenzamides to Pd(OAc)2, Cs2CO3 and a phosphine leads to debrominative coupling and cyclization with elimination of one amide unit, to give phenanthridinones.15 CONHR + Br

O Pd(OAc)2–Cs2CO3

CONHR

NR

Br Ph2P

OMe

A remarkable change of the second-stage coupling described in the following equations is apparently the effect of the base employed.16

Pd(OAc)2–t-BuONa

NHBoc

H

NBoc H

PhMe PPh2

Ph

90o

O PPh2

Br H

+

Pd(OAc)2–Cs2CO3

Ph

diox. PPh2

PPh2

Ph

H

100o

O

BocNH

The possibility of Pd shift, as exempliﬁed by cases of o-iodobiaryls,17 must be heeded. On the other hand, the phenomenon can be used to synthetic advantage, as shown by an unusual route to ﬂuorenones, xanthones, and acridones.18

X

Pd(OAc)2 Bu4NCl, NaHCO3 DMF 100o

COOEt

X

X = Me, OMe (+ 1,4-shift product ) I +

COOEt

X

Pd(OAc)2 DPPM, t-BuCOOCs DMF 100o

EtOOC X = NO2, COOEt

332

Palladium(II) acetate – tertiary phosphine

Z

Pd(OAc)2

N H

Z

DPPM, t-BuCOOCs

NPh

DMF 100o

I Z = O, NMe

The transient involvement of norbornene in Heck reaction via its carbopalladation and help to functionalization of the ortho position(s) is highly proﬁtable. Its further exploitation includes o-alkylation at the site of Heck reaction19 and amination.20 Y I

Br

Br

Ph3P, Cs 2CO3

Z

X

X

X = O, S, NTs....

Z

Pd(OAc)2

Y

+

w

X

X

Y = CN,SO2Ph, COOR

The process is applicable to completing an exchange of the halogen atom to a CN group by reaction with K4Fe(CN)6, after performing o-functionalization.21 In another report on the preparation of ArCN, the bulky butylbis(1-adamantyl)phosphine is the ligand employed.22 R'

R I +

R Pd(OAc)2

HN

2-Fu3P, Cs 2CO3

R' N n

MeCN 135o

Br

Pd(OAc)2

N N

O Ph

+

PhMe

Br

O

125o

N H

N N

t-Bu3P, K2CO3

N

N

Ph N

anabasine 83%

Pd(OAc)2 t-Bu3PHBF4, K2CO3 PhMe

N O

N O

110o

+ ArBr (dba)3Pd2 X-Phos

Ar

N O

Ar

Palladium(II) acetate – tertiary phosphine

333

Directed activation of the CZH bond adjacent to the nuclear nitrogen atom of N-iminopyridinium ylides enables a rapid elaboration of a synthetic intermediate of anabasine.23 2-Picoline-N-oxide undergoes coupling with ArBr at C-6. Interestingly, the reaction is shifted to the methyl group by changing the catalyst system to (dba)3Pd2/X-Phos,24 or Pd(OAc)2/DavePhos.25 Cross-coupling of two different types of alkynes in a controlled and atom-economical fashion is of great synthetic value. By this method, 2-alken-4-ynoic esters are readily elaborated.26 Pd(OAc)2

N N

O

+

ArCl

O

Me2N

Ph

Ar

N N

Cs2CO3, DMF

Ph PCy2

MeOOC

+

COOMe

OR HO

Pd(OAc)2

HO

OTBS

OMe

OTBS

P3 OMe

OR

SiMe3

SiMe3

Alkenylation and arylation. Alkenyl triﬂates are highly active in intramolecular alkenylation of both electron-rich and electron-poor arenes.27 2-Alkynylbiaryls give 9-alkylideneﬂuorenes via palladation of the o 0 -position [the benzene ring bearing electron-withdrawing group(s)].28

X R

X

Pd(OAc)2–DPPP

OTf

Bu3N, NMP 80o

R

R = H, Me X = Cl, F, CN, OMe... X

X Pd(OAc)2 iPr2P Fe

R

iPr2P

PhMe 120o

R

334

Palladium(II) acetate – tertiary phosphine

a-Methallyl-g-bromocinnamyl alcohols undergo cyclization to provide 3-aryl-4,4dimethyl-2-cyclopentenones.29 Some members of this series of compounds are useful precursors of cuparan sesquiterpenes.

Pd(OAc)2

Br

Ar

Ph3P, Na2CO3

OH

DMF 80o

Ar

O

Phenanthrenes spanned at C-4 and C-10 by an aminomethyl bridge emerge from cyclization of N-(m-bromoaryl)-b-bromocinnamylamines.30 The reaction involves double CZH activation.

NR Pd(OAc)2

Br

NR

Cy3PHBF4, Cs2CO3 dioxane

Br

Many metal-catalyzed reactions of propargylic esters proceed as if alkylidene-metal carbenoids are involved. In the Pd-catalyzed reaction such species add to norbornenes/ norbornadienes to give ring expansion products.31 R +

R

OAc

R

Pd(OAc)2

R

CyP(Ph)OH PhMe 60o

OAc

For a-arylation of aldehydes catalytic systems with wide-scoped applicability have been determined.32 Excellent phosphine ligand for assisting Pd(OAc)2 in the reaction with ArCl is 1, and with ArBr, rac. BINAP or 2.

MeO

i-Pr2P

MeO OMe

(1)

PCy2

(2)

Coupling via C(sp3)-H activation. In addition to some examples mentioned in the previous section (e.g., 2-picoline derivatives), sp 3-hybridized CZH can be activated with Pd catalysts under proper conditions. Such a process enables formation of indolines33 and dihydrobenzofurans.34

Palladium(II) acetate – tertiary phosphine

Br X

R'

Pd(OAc)2

R"

R

Cy3PHBF4, Cs2CO3

R'

335

X

R"

t-BuCOOH xylene

X = O, NCOOMe R = OMe, NO2…

A benzylic alkyl group of o-bromoarylacetonitriles or the corresponding arylacetic esters is either dehydrogenated with one hydrogen atom to replace the bromine atom, or engaged in ring formation. The catalyst system to effect the transformation(s) consists of Pd(OAc)2 and tris(m-ﬂuorophenyl)phosphine.35 Br

H

Pd(OAc)2 K2CO3,

X

DMF 100o

F 3

X

P

X = CN 77% X = COOEt 67% Br

H

Pd(OAc)2 K2CO3, DMF 100o

NC

F 3

NC

P

62%

Allylic substitution. a-Triﬂuoromethylcinnamyl acetate undergoes substitution with R2NH. Regiochemical contrasts are observed in reactions with different catalyst systems.36 NR2

Pd(OAc)2 DPPE, THF

OAc Ph

Ph

CF3

CF3 + R2NH

NR2

Pd(cod) BF4 DPPF, dioxane

Ph

CF3

In the presence of (i-PrO)4Ti, an allylic alcohol unit serves as a leaving group and a secondary hydroxyl group as a nucleophile in Pd-catalyzed cyclization.37

OH R

OH

Pd(OAc)2 Ph3P, (i PrO)4Ti PhMe

R

O

336

Palladium(II) acetate – tertiary phosphine

Catalysts for diallylation of active methylene compounds (e.g., malonate esters) and RCM reaction are compatible, therefore 3-cyclopentene-1,1-dicarboxylic esters can be prepared in one-pot.38

MeOOC

COOMe

MeOOC

COOMe

Pd(OAc)2 Ph3P, NaH, Grubbs II CH2Cl2

+ OAc

100%

Two stereogenic centers are established on allylation of a-substituted b-keto esters and cyanoacetic esters with secondary cinnamyl acetates. The reaction is directed toward a regioselective and diastereoselective pathway when o-diphenylphosphinobenzoic acid is used as a ligand.39

R' R

OAc

+ COOEt

R"

R"

Pd(OAc)2

R' R

NaHMDS

Ar

O

PPh2

COOEt

Ar

O

COOH

Epimerization. Treatment of (Z)-g-(2-bromovinyl)-g-butyrolactones with Pd(OAc)2 and Ph3P simultaneously inverts the less stable stereocenter and change the double bond conﬁguration via formation of p-allylpalladium species from which reclosure of the lactone ring follows CC bond rotation. This stereochemical readjustment is an important operation in an approach to 4-epiethisolide.40

H O

H O O

Pd(OAc)2

O

O H

H O

O

Br

Ph3P THF

O

O

O

O

H

O H

Br 87%

4-epiethisolide

Reduction. Hydrodehalogenation of ArX and a-bromo ketones is accomplished by heating the halides with Pd(OAc)2, Ph3P and K2CO3 in an alcohol at 1008.41 Enol triﬂates are defunctionalized by the Pd-catalyzed reduction with HCOOH – Bu3N in DMF.42

Palladium(II) acetate – tertiary phosphine

337

Selective hydrogenation of alkenes such as the strained double bond of dicyclopentadiene is achieved by heating with Pd(OAc)2, t-Bu3P and HCOOH in THF.43 Addition reactions. Acrylic esters and analogues (amides, nitriles) are receptive to aryl group transfer to their b-position from ArB(OH)2, under the inﬂuence of Pd(OAc)2.44

ArB(OH)2

Pd(OAc)2

+

X

Ar X

(PhO)3P, K3PO4

X = CN, COOR, CONMe2

(air) DMF

Complementary to copper catalyst, a Pd(OAc)2 – Ph3P system also promotes the conjugate addition of R2Zn to enals.45 With Pd insertion into a CZSi bond of a siletane elements of the small ring add to conjugated carbonyl compounds, eight-membered unsaturated O,Si-heterocycles are produced.46

SiMe2 Pd(OAc)2

+ R

O

Cy3P / THF

R

SiMe2 O R'

R'

1

Reddy, C.V., Kingston, J.V., Verkade, J.G. JOC 73, 3047 (2008). Kingston, J.V., Verkade, J.G. JOC 72, 2816 (2007). 3 Billingsley, K.L., Barder, T.E., Buchwald, S.L. ACIE 46, 5359 (2007). 4 Fang, Y.-Q., Lautens, M. JOC 73, 538 (2008). 5 Yu, S.-B., Hu, X.-P., Deng, J., Huang, J.-D., Wang, D.-Y., Duan, Z.-C., Zheng, Z. TL 49, 1253 (2008). 6 Liu, Z., Xu, D., Tang, W., Xu, L., Mo, J., Xiao, J. TL 49, 2756 (2008). 7 Hyder, Z., Ruan, J., Xiao, J. CEJ 14, 5555 (2008). 8 Uemura, M., Yorimitsu, H., Oshima, K. T 64, 1829 (2008). 9 Iwasaki, M., Hayashi, S., Hirano, K., Yorimitsu, H., Oshima, K. T 63, 5200 (2007). 10 Hayashi, S., Hirano, K., Yorimitsu, H., Oshima, K. JACS 129, 12650 (2007). 11 Ethirajan, M., Oh, H.-S., Cha, J.K. OL 9, 2693 (2007). 12 Tietze, L.F., Redert, T., Bell, H.P., Hellkamp, S., Levy, L.M. CEJ 14, 2527 (2008). 13 Guo, L.N., Duan, X.-H., Liu, X.-Y., Hu, J., Bi, H.-P., Liang, Y.-M. OL 9, 5425 (2007). 14 Ackermann, L., Althammer, A. ACIE 46, 1627 (2007). 15 Furuta, T., Kitamura, Y., Hashimoto, A., Fujii, S., Tanaka, K., Kan, T. OL 9, 183 (2007). 16 Bertrand, M.B., Wolfe, J.P. OL 9, 3073 (2007). 17 Campo, M.A., Zhang, H., Yao, T., Ibdah, A., McCulla, R.D., Huang, Q., Zhao, J., Jenks, W.J., Larock, R.C. JACS 129, 6298 (2007). 18 Zhao, J., Yue, D., Campo, M.A., Larock, R.C. JACS 129, 5288 (2007). 2

338

Palladium(II) acetate – tertiary phosphine – carbon monoxide

19

Alberico, D., Rudolph, A., Lautens, M. JOC 72, 775 (2007). Thansandote, P., Raemy, M., Rudolph, A., Lautens, M. OL 9, 5255 (2007). 21 Mariampillai, B., Alliot, J., Li, M., Lautens, M. JACS 129, 15372 (2007). 22 Schareina, T., Zapf, A., Ma¨gerlein, W., Mu¨ller, N., Beller, M. TL 48, 1087 (2007). 23 Larivee, A., Mousseau, J.L., Charette, A.B. JACS 130, 52 (2008). 24 Campeau, L.-C., Schipper, D.J., Fagnou, K. JACS 130, 3266 (2008). 25 Mousseau, J.J., Larivee, A., Charette, A.B. OL 10, 1641 (2008). 26 Trost, B.M., Ashfeld, B.L. OL 10, 1893 (2008). 27 Cruz, A.C.F., Miller, N.D., Willis, M.C. OL 9, 4391 (2007). 28 Chernyak, N., Gevorgyan, V. JACS 130, 5636 (2008). 29 Ray, D., Ray, J.K. OL 9, 191 (2007). 30 Ohno, H., Iuchi, M., Fujii, N., Tanaka, T. OL 9, 4813 (2007). 31 Bigeault, J., de Riggi, I., Gimbert, Y., Giordano, L., Buono, G. SL 1071 (2008). 32 Martin, R., Buchwald, S.L. ACIE 46, 7236 (2007). 33 Watanabe, T., Oishi, S., Fujii, N., Ohno, H. OL 10, 1759 (2008). 34 Lafrance, M., Gorelsky, S.I., Fagnou, K. JACS 129, 14570 (2007). 35 Hitce, J., Retailleau, P., Baudoin, O. CEJ 13, 792 (2007). 36 Kawatsura, M., Hirakawa, T., Tanaka, T., Ikeda, D., Hayase, S. Itoh, T. TL 49, 2450 (2008). 37 Brioche, J.C.R., Goodenough, K.M., Whatrup, D.J., Harrity, J.P.A. JOC 73, 1946 (2008). 38 Kammerer, C., Prestat, G., Gaillard, T., Madec, D., Poli, G. OL 10, 405 (2008). 39 Kawatsura, M., Ikeda, D., Komatsu, Y., Mitani, K., Tanaka, T., Uenishi, J. T 63, 8815 (2007). 40 Hon, Y.-S., Chen, H.-F. TL 48, 8611 (2007). 41 Chen, J., Zhang, Y., Yang, L., Zhang, X., Liu, J., Li, L., Zhang, H. T 63, 4266 (2007). 42 Pandey, S.K., Greene, A.E., Poisson, J.-F. JOC 72, 7769 (2007). 43 Brunel, J.M. SL 330 (2007). 44 Horiguchi, H., Tsurugi, H., Satoh, T., Miura, M. JOC 73, 1590 (2008). 45 Marshall, J.A., Herold, M., Eidam, H.S., Eidam, P. OL 8, 5505 (2006). 46 Hirano, K., Yorimitsu, H., Oshima, K. OL 10, 2199 (2008). 20

Palladium(II) acetate – tertiary phosphine – carbon monoxide. Carbonylation. The conversion of ArOTf to ArCHO with syngas (reductive carbonylation) simply uses the Pd(OAc)2 – DPPP system as catalyst.1 Homologation of cycloalkenyl triﬂates to the corresponding enals is perhaps favored by the hindered bisphosphine 1.2

P OTf

Pd(OAc)2 (1)

P

(1)

CO / H2

CHO

Palladium(II) bis(triﬂuoroacetate)

339

Without the reducing agent (e.g., H2) aryl sulfonates are converted into esters in ROH under basic conditions (a protocol indicates addition of the hydroﬂuoroborate salt of 1,3biscyclohexylphosphinopropane).3 In an analogous synthesis of amides in DMSO, in which amines replace ROH, the PhONa base appears to play a special and critical role.4 With Al(OTf)3 cocatalyst 1-alkenes are transformed into saturated esters favoring the linear isomer (against the branched isomer in a ratio of .2 : 1).5 A general method for preparation of ArCOAr0 from ArB(OH)2, Ar 0 Br and CO employs Pd(OAc)2, butylbis(1-adamantyl)phosphine and TMEDA.6 Carboxylation. Arylzinc bromides undergo carboxylation with CO2 readily.7 The Pd catalyst (with Cy3P as ligand) performs better than a similar Ni complex. 1

Brennfu¨hrer, A., Neumann, H., Beller, M. SL 2537 (2007). Neumann, H., Sergeev, A., Beller, M. ACIE 47, 4887 (2008). 3 Munday, R.H., Martinelli, J.R., Buchwald, S.L. JACS 130, 2754 (2008). 4 Martinelli, J.R., Clark, T.P., Watson, D.A., Munday, R.H., Buchwald, S.L. ACIE 46, 8460 (2007). 5 Williams, D.B.G., Shaw, M.L., Green, M.J., Holzapfel, C.W. ACIE 47, 560 (2008). 6 Neumann, H., Brennfu¨hrer, A., Beller, M. CEJ 14, 3645 (2008). 7 Yeung, C.S., Dong, V.M. JACS 130, 7826 (2008). 2

Palladium(II) acetylacetonate. Coupling reactions. Electron-deﬁcient aroic acids undergo decarboxylative coupling with ArBr on heating with Pd(acac)2, CuCO3.1 Allylsilanes are prepared from allyl ethers (silyl ethers or phenyl ethers) and R3SiCl; coupling takes place in the presence of Pd(acac)2 and PhMgBr (240 mol%).2 Stereoselective cyclization of 6-hydroxy-4-hexenals is observed. 2-Vinylcyclobutanols are obtained.3

CHO

Pd(acac)2

R R'

OH

Bu3P / Et3B THF 50o

HO RL Rs

1

Goossen, L.J., Rodriguez, N., Melzer, B., Linder, C., Deng, G., Levy, L.M. JACS 129, 4824 (2007). Naitoh, Y., Bando, F., Terao, J., Otsuki, K., Kuniyasu, H. CL 36, 236 (2007). 3 Kimura, M., Mukai, R., Tamaki, T., Horino, Y., Tamaru, Y. JACS 129, 4122 (2007). 2

Palladium(II) bis(triﬂuoroacetate). Decarboxylation. Aroic acids bearing electronic-rich substituents are found to undergo decarboxylation on warming with Pd(OCOCF3)2, CF3COOH in DMF (containing 5% DMSO) at 708.1

340

Palladium(II) bis(triﬂuoroacetate)

Dehydrogenation. Cycloalkanones are converted into the corresponding enones by the Pd-catalyzed aerial oxidation in the presence of a bipyridyl ligand.2

Coupling reactions. Aryl cyanides are formed in a reaction with Zn and Zn(CN)2, using t-Bu3P to ligate with Pd(OCOCF3)2 [or (t-Bu3P)2Pd].3 The coupling of o-borylaroic esters with alkynes is immediately followed by acylation, which results in the formation of indenones. The homologous arylacetic esters give 2-naphthols.4

R B(OH)2

R

Pd(OCOCF3)2

+

80o

R

O B O COOMe

R

DPPE, MeOH

COOMe

O R

R

R

Pd(OCOCF3)2

+ R

DPPE, MeOH

OH

80o

R'

R'

Cyclization of o-allyl-N-tosylarylamines to afford 2-vinylindolines is accomplished by Pd(OCOCF3)2 and a carbene ligand (1) in oxygen (or air).5

R NHTs N

N

Pd(OCOCF3)2 HOAc (stabilizer) O2, PhMe 80o

(1) R N Ts R=H

84%

Regiochemical dependency in the oxidative coupling of N-acetylindole with arenes on the added oxidant [AgOAc vs. Cu(OAc)2] is a remarkable phenomenon.6

Palladium(II) bis(triﬂuoroacetate)

341

Pd(OCOCF3)2 Cu(OAc)2

N Ac

+ N R

O Pd(OCOCF3)2

N

AgOAc

O

Using benzoquinone as oxidant to regenerate Pd(II) species in situ in the reaction catalyzed by Pd(OCOCF3)2, a 3,5-bridged tetrahydropyran is formed from 2,2-diprenyl1,3-propanediol monobenzoate. Asymmetric induction by a spiro(isoxazole-isoxazoline) ligand has also been scrutinized.7

OBz

Pd(OCOCF3)2 benzoquinone

OH

O

MeOH–CH2Cl2

OBz

0o

H

ligand : O

NN

O

Aryl(2-pyridyl)methanes are obtained from coupling of picolyl diisopropyl carbinol with ArCl. The reaction involves fragmentation to form aryl(2-methylene-1,2-dihydropyridyl)palladium intermediates.8 1

Dickstein, J.S., Mulrooney, C.A., O’Brien, E.M., Morgan, B.J., Kozlowski, M.C. OL 9, 2441 (2007). Tokunaga, M., Harada, S., Iwasawa, T., Obora, Y., Tsuji, Y. TL 48, 6860 (2007). 3 Littke, A., Soumeillant, M., Kaltenbach III, R.F., Cherney, R.J., Tarby, C.M., Kiau, S. OL 9, 1711 (2007). 4 Tsukamoto, H., Kondo, Y. OL 9, 4227 (2007). 5 Rogers, M.M., Wendlandt, J.E., Guzei, I.A., Stahl, S.S. OL 8, 2257 (2006). 6 Stuart, D.R., Villemure, E., Fagnou, K. JACS 129, 12072 (2007). 7 Koranne, P.S., Tsujihara, T., Arai, M.A., Bajracharya, G.B., Suzuki, T., Onitsuka, K., Sasai, H. TA 18, 919 (2007). 8 Niwa, T., Yorimitsu, H., Oshima, K. ACIE 46, 2643 (2007). 2

342

Palladium carbene complexes

Palladium carbene complexes. Coupling reactions. A PdCl2 complex with 1,3-bis(2,6-diisopropylphenyl)imidazol2-ylidene and 3-chloropyridine ligands is active for catalyzing the Suzuki coupling.1 Hydrogenation. In a polar solvent, the Pd species ligated by both 1,3-dimesitylimidazol2-ylidene and maleic anhydride promotes hydrogenation of alkynes to give (Z )-alkenes by HCOOHZNEt3 without over-reduction.2 On the other hand, complexes 1 with a very basic and electron-rich Pd center serves as a hydrogenation catalyst for alkenes.3 In comparison, the less basic 1a is a poor catalyst.

N

N

N

N

N N

Pd N

N

2 BF4

R

(1)

N Pd

N

N N R

2 BF4

(1a)

1

Valente, C., Baglione, S., Candito, D., O’Brien, C.J., Organ, M.G. CC 735 (2008). Hauwert, P., Maestri, G., Sprengers, J.W., Catellani, M., Elsevier, C.J. ACIE 47, 3223 (2008). 3 Heckenroth, M., Kluser, E., Neels, A., Albrecht, M. ACIE 46, 6293 (2007). 2

Palladium(II) chloride. Benzhydryl ethers. Alcohols and benzhydrol condense to form ROCHPh2 on warming with PdCl2 at 808.1 Alkylation. Viologen-supported nanoparticles of palladium prepared from PdCl2 show an activity of promoting alkylation of methyl ketones with alcohols in the air at 1008. A 1,3-cycloalkanedione undergoes alkylation but the ring is opened. The reaction also requires a base such as Ba(OH)2 . H2O or Sr(OH)2 . 8H2O.2 Allylation of 1,3-dicarbonyl compounds catalyzed by PdCl2 –Bu4NBr is subject to solvent effects. Diallylation occurs in THF, but in water, monoallylation.3 Coupling reactions. The coupling of 1,2-diiodoalkenes with 1-alkenes affords conjugated enynes, as dehydroiodination also occurs. The (E)-isomer is produced from acrylonitrile, (Z )-isomers from other alkenes.4 R

I +

I

R'

PdCl2 BuNBr, Na 2CO3 H2O 80o

CHR' R (E ) R' = COOMe (Z ) R' = CN

For Suzuki coupling, amine ligands tested to support PdCl2 include polyaniline,5 2-(2-pyridyl)-6-isopropylpiperidine,6 and piperazine 1.7 The naphthidine 2 actually reduces PdCl2 to Pd(0) nanoparticles and stabilizes such to perform catalysis.8

Palladium(II) chloride

N

343

OMe 2

HO

N

N

OH MeO

N 2

(1)

(2)

With a cationic 2,20 -bipyridyl ligand the Suzuki coupling in water proceeds very efﬁciently (TOF up to 81,000 per hr, TON up to 395,000).9 Exploration of metal-carbene complexes in catalysis for various reactions is in vogue. Performing Heck reaction in the ionic liquid N-methyl-N0 -(2-diisopropylaminoethyl)imidazolium triﬂimide must involve a carbene-complexed Pd species.10 An N-arylation method to derivatize amines has been developed in that spirit.11

Cyclopentenones. 3-Acetoxy-4-alken-1-ynes are converted into cyclopentenones on treatment with PdCl2 in MeCN at 608 (or with in CH2Cl2 at room temperature).12

O

AcO PdCl 2

R

MeCN 60o

R'

R' R"

1

R

R"

Bikard, Y., Weibel, J.-M., Sirlin, C., Dupuis, L., Loefﬂer, J.-P., Pale, P. TL 48, 8895 (2007). Yamada, Y.M.A., Uozumi, Y. T 63, 8492 (2007). 3 Ranu, B.C., Chattopadhyay, K., Adak, L. OL 9, 4595 (2007). 4 Ranu, B.C., Chattopadhyay, K. OL 9, 2409 (2007). 5 Kantam, M.L., Roy, M., Roy, S., Sreedhar, B., Madhavendra, S.S., Choudary, B.M., De, R.L. T 63, 8002 (2007). 6 Puget, B., Roblin, J.-P., Prim, D., Troin, Y. TL 49, 1706 (2008). 7 Mohanty, S., Suresh, D., Balakrishna, M.S., Mague, J.T. T 64, 240 (2008). 8 Desmarets, C., Omar-Amrani, R., Walcarius, A., Lambert, J., Champagne, B., Fort, Y., Schneider, R. T 64, 372 (2008). 9 Wu, W.-Y., Chen, S.-N., Tsai, F.-Y. TL 47, 9267 (2006). 10 Ye, C., Xiao, J.-C., Twamley, B., LaLonde, A.D., Norton, M.G., Shreeve, J.M. EJOC 5095 (2007). 11 Organ, M.G., Abdel-Hadi, M., Avola, S., Dubovyk, I., Hadei, N., Assen, E., Kantchev, B., O’Brien, C.J., Sayah, M., Valente, C. CEJ 14, 2443 (2008). 12 Caruana, P.A., Frontier, A.J. T 63, 10646 (2007). 2

344

Palladium(II) chloride – di-t-butylphosphinous acid

Palladium(II) chloride – di-t-butylphosphinous acid. Hydroarylation. The transfer of the aryl group of ArSi(OMe)3 to the b-position of conjugated ketones, esters, nitriles, and nitroalkenes can be carried out in water with a Pd–Cu salt combinant such as (t-BuPOH)PdCl2 and CuBF4.1 1

Lerebours, R., Wolf, C. OL 9, 2737 (2007).

Palladium(II) chloride – metal salts. Coupling reactions. To form biaryls through cross-coupling of ArCOOH with Ar 0 I, one of the aryl groups in the products comes from decarboxylation of the acids. The catalyst system used to effect this reaction contains PdCl2, Ph3As and Ag2CO3.1 Arenes undergo coupling with ArSnCl3 in the presence of a bimetallic catalyst of PdCl2 and CuCl2.2 An o-position of N,N-dimethylbenzylamines is also activated toward coupling with acrylic acid derivatives.3 Ar PdCl2

+ ArSnCl3

CuCl2 ClCH2CH2Cl 80o

PdCl2

+ ArSnCl3

CuCl2 ClCH2CH2Cl 80o

Ar

NMe2

NMe2

PdCl2

R + X

Cu(OAc)2

R

(HOAc)

X

CF3 CH2OH 85o

X = COOR, CONH2...

A method for preparing unsymmetrical 1,2-diarylethyne based on Sonogashira coupling, 1-ethynylcyclohexanol is employed. The two-stage process is intervened by the addition of KOH (after completion of the ﬁrst coupling) to release arylethynes.4

OH

ArX

OH

(Ph3P)2PdCl2 CuI i-Pr2NH

Ar'X

Ar

(Ph3P)2PdCl2 CuI

Ar

i-Pr2NH

Ar'

Palladium(II) chloride – metal salts

345

3-Aminoindolizines are readily obtained from the coupling of 2-bromopyridines and propargylamines,5 whereas precursors of indolines can be assembled from an N-protected propargylamine by extending the carbon chain to an enyne and completing N-alkynylation. Thermolysis of such products gives substituted indolines.6 + N

(Ph3P)2PdCl2

N

CuI

Br

R2N

DBU / AcNMe2

R2N

(Ph3P)2PdCl2

+ N H

COOMe

SiMe3

pyrrolidine;

Br

CuI, Py, KHMDS Br

N COOMe

SiMe3

180o

SiMe3 N COOMe 74%

2-Arylethylamines form N-(2-arylethyl)-3,4-diarylpyrroles in a trimerizative condensation on treatment with PdCl2 –Cu(OAc)2.7 Ring expansion.8 2-Arylidenecyclopropane-1-methanols possessing electron-rich aryl groups undergo ring expansion to afford cyclobutenemethanols under argon, when they are exposed to PdCl2 –CuBr2. On the other hand, electron-poor congeners give hydrofuran derivatives under air. OH PdCl2 –CuBr 2 NaHCO3, CH2Cl2

OH Ar

Ar

Ar / 0o

Br PdCl2 –CuBr 2

Br +

NaHCO3, CH2Cl2 air / 25o

Ar

O

Ar

Ar electron-poor

O

346

Palladium(II) chloride – tertiary phosphine

Wacker oxidation. Directed by an allylic triﬂuoroacetamido group a terminal double bond is converted into an aldehyde as the major product. The transformation has been exploited in a synthesis of daunosamine.9 NHCOCF3

NHCOCF3 CHO

PdCl2 –CuCl

O

O2, HMPA

O O

O

major (aldehyde:ketoene 82:18)

Under reaction conditions essentially those for the Wacker oxidation, electron-deﬁcient 1-alkenes (e.g., acrylic esters) are trimerized to provides 1,3,5-trisubstituted benzenes.10 Pauson –Khand reaction. In the Pd-catalyzed reaction tetramethylthiourea and LiCl are important additives.11 1

Becht, J.-M., Catala, C., Le Drian, C., Wagner, A. OL 9, 1781 (2007). Kawai, H., Kobayashi, Y., Oi, S., Inoue, Y. CC 1464 (2008). 3 Cai, G., Fu, Y., Li, Y., Wan, X., Shi, Z. JACS 129, 7666 (2007). 4 Csekei, M., Novak, Z., Kotschy, A. T 64, 975 (2008). 5 Liu, Y., Song, Z., Yan, B. OL 9, 409 (2007). 6 Dunetz, J.R., Danheiser, R.L. JACS 127, 5776 (2005). 7 Wan, X., Xing, D., Fang, Z., Li, B., Zhao, F., Zhang, K., Yang, L., Shi, Z. JACS 128, 12046 (2006). 8 Tian, G.-Q., Yuan, Z.-L., Zhu, Z.-B., Shi, M. CC 2668 (2008). 9 Friestad, G.K., Jiang, T., Mathies, A.K. OL 9, 777 (2007). 10 Jiang, H.-F., Shen, Y.-X., Wang, Z.-Y. TL 48, 7542 (2007). 11 Deng, L.-J., Liu, J., Huang, J.-Q., Hu, Y., Chen, M., Lan, Y., Chen, J.-H., Lei, A., Yang, Z. S 2565 (2007). 2

Palladium(II) chloride – tertiary phosphine. Hydrodehalogenation. Removal of halogen atom(s) from haloarenes is accomplished by heating with PdCl2, DPPF, NaHCO3 in DMF, the solvent is a convenient hydride source.1 Arylation. With the highly active and air-stable ligand, 1,10 -bis(di-t-butylphosphino)ferrocene, to assist PdCl2, a-arylation of ketones can be accomplished in good yields even with the hindered 2,6-dimethylchlorobenzene.2 More unusual is the arylation that converts enol acetates into aryl ketones as shown below.3 The reaction employs Bu3SnOMe as base. AcO ArBr

R

+ R'

O PdCl2 –(o-Tol )3P Bu3SnOMe DMSO 100°

R'

Ar R

2-Arylthiazoles are found to undergo arylation at C-5. Cleaner and faster reactions are performed in water than in other common solvents.4 Arylation of 4-aryl-1,2,3-triazoles has also been reported.5

Palladium(II) chloride – tertiary phosphine

347

An alkynyl group is introduced into C-3 of the indolizine nucleus by the Pd-catalyzed reaction with a 1-alkyne.6

N

(Ph3P)2PdCl2

+

N

KOAc

R

R

PhMe

Coupling reactions. The PdCl2 –DPPF system placed in a microemulsion environment (SDS, NaHCO3) can be used to catalyze Suzuki coupling of long-chain alkyl and oxyalkyl substrates.7 Heck reaction in the presence of the aminoethylimidazolium salt 1 requires no additional base.8 Using the 1,10 -bis(di-t-butylphosphino)ferrocene ligand Heck reaction is accomplished at room temperature in water to prepare styrenes and cinnamate esters.9 The same conditions are conducive to performing Suzuki coupling.10

N

N

N

Tf2N

(1) Azolecarbene ligands are shown to be favorable to Suzuki coupling involving polyﬂuorinated aryltriﬂuoroborate salts (e.g., C6F5BF3K) catalyzed by (Ph3P)2PdCl2 under anaerobic conditions.11 Formation of 3-spiroannulated oxindoles involving a Heck reaction is the result of subsequent activation of a proximal aromatic CZH bond by the organopalladium complex.12

Br (Ph3P)2PdCl2

N R

Cs2CO3

O

O

DMF

N R

1,2-Migration of alkenyl-Pd(II) intermediates may occur during Heck reaction of enol phosphates, but it may be suppressed by using the X-Phos ligand.13

348

Palladium(II) chloride – tertiary phosphine

(cod)PdCl2 –LiCl

R

X-Phos, Cy2NMe

OPh O

+

P OPh O (cod)PdCl2 –LiCl

R

tBu3PHBF4, Cy2NMe

R

a-Substituted styrenes are synthesized from 1-alkynes by hydroarylation, using NaBAr4 (e.g., ArvPh) as reagents.14 Hydroalkenylation of alkynes, via hydropalladation, proceeds well with acrylic esters and amides.15

R

(cod)PdCl2 –LiCl

Y

+

t-Bu3PHBF4, DMF

R'

Y

R R'

Y = COOR, CONHR

Another copper-free protocol of Sonogashira coupling instructs heating ArBr, 1-alkynes with PdCl2, Ph3P in pyrrolidine containing water at 1208.16 Silylalkynes and propargylic chlorides couple with loss of both functional groups, affording alka-1,2-dien-4-ynes.17

Cl Ar

SiMe3

C

(Ph3P)2PdCl2

+

CuI, Bu4NF DMF

R

Ar R

Ring formation. Imines derived from o-alkynylaraldehydes react with chloroform to give 1-trichloromethyl-1,2-dihydroisoquinolines.18 R

R (Ph3P)2PdCl2

N

DPPE, CHCl3

R'

100

o

NR' CCl3

Carbonylation follows the formal alkenylation of 1,3-dicarbonyl compounds, therefore 5-acyl-3,4-dihydro-2-pyrones can be assembled from the Pd-catalyzed reaction involving alkynes and CO.19

Palladium(II) hydroxide/carbon

O

CO R"

O

R

O

349

R

(Ph3P)2PdCl2

R'

+ O

R"'

DPPP ionic liq. 110 o

R'

R" R"'

O

1

Zawisza, A.M., Muzart, J. TL 48, 6738 (2007). Grasa, G.A., Colacot, T.J. OL 9, 5489 (2007). 3 Jean, M., Renault, J., Uriac, P., Capet, M., van de Weghe, P. OL 9, 3623 (2007). 4 Turner, G.L., Morris, J.A., Greaney, M.F. ACIE 46, 7996 (2007). 5 Chuprakov, S., Chernyak, N., Dudnik, A.S., Gevorgyan, V. OL 9, 2333 (2007). 6 Seregin, I.V., Ryabova, V., Gevorgyan, V. JACS 129, 7742 (2007). 7 Vashehenko, V., Krivoshey, A., Knyazeva, I., Petrenko, A., Goodby, J.W. TL 49, 1445 (2008). 8 Ye, C., Xiao, J.-C., Twamley, B., LaLonde, A.D., Norton, M.G., Shreeve, J.M. EJOC 5095 (2007). 9 Lipshutz, B.H., Taft, B.R. OL 10, 1329 (2008). 10 Lipshutz, B.H., Petersen, T.B., Abela, A.R. OL 10, 1333 (2008). 11 Adonin, N.Yu., Babushkin, D.E., Parmon, V.N., Bardin, V.V., Kostin, G.A., Mashukov, V.I., Frohn, H.-J. T 64, 5920 (2008). 12 Ruck, R.T., Huffman, M.A., Kim, M.M., Shevlin, M., Kandur, W.V., Davies, I.W. ACIE 47, 4711 (2008). 13 Ebran, J.-P., Hansen, A.L., Gogsig, T.M., Skrydstrup, T. JACS 129, 6931 (2007). 14 Zeng, H., Hua, R. JOC 73, 558 (2008). 15 Lindhardt, A.T., Mantel, M.L.H., Skrydstrup, T. ACIE 47, 2668 (2008). 16 Guan, J.T., Weng, T.Q., Yu, G.-A., Liu, S.H. TL 48, 7129 (2007). 17 Girard, D., Broussons, S., Provot, O., Brion, J.-D., Alami, M. TL 48, 6022 (2007). 18 Nakamura, H., Saito, H., Nanjo, M. TL 49, 2697 (2008). 19 Li, Y., Yu, Z., Alper, H. OL 9, 1647 (2007). 2

Palladium(II) hydroxide/carbon. Deprotection.1 Cleavage of benzyl ethers and cyclic acetals by heating with large amounts of this catalyst [20% Pd(OH)2/C] in MeOH is totally impractical. It does not seem to offer any advantage over the less expensive Pd/C. Hydrogenation. An interesting transfer hydrogenation (with double bond migration) that converts 1,3-dihydroindoles to 4,5,6,7-tetrahydroisoindoles is catalyzed by Pd(OH)2/C.2 Pd(OH)2 /C

NR

HCOONH4, MeOH

NR

A benzylic nitro group is hydrogenolyzed in the presence of Pd(OH)2, whereas homogeneous catalysts are ineffective and only low conversion is observed with Pt/C (and with Rh/C hydrogenation to amines occurs).3 In conjunction with an enantioselective Henry reaction, chiral homobenzylic alcohols are accessible. 1

Murali, C., Shashidhar, M.S., Gopinath, C.S. T 63, 4149 (2007). Hou, D.-R., Wang, M.-S., Chung, M.-W., Hsieh, Y.-D., Tsai, H.-H.G. JOC 72, 9231 (2007). 3 Fesard, T.C., Motoyoshi, H., Carreira, E.M. ACIE 46, 2078 (2007). 2

350

Palladium(II) iodide

Palladium(II) iodide. Oxidation. Benzils are formed on heating diarylethynes with PdI2 and DMSO at 1408.1 Coupling.2 Palladation of allenyl carbinols leads to 2,5-dihydrofuran intermediates that contain a CZPd bond at C-3. Such intermediates can undergo coupling with unreacted allenyl carbinols. Because substitution at the b-carbon affects rates of palladation two different carbinols can be joined. R" R

OH +

R" C

R

PdI2 , BF3 · OEt2

C R' HO

DMSO 80o

R'

O

Coumarin synthesis.3 Double carbonylation is involved when a-(o-hydroxyaryl)parpargyl alcohols are placed in an autoclave with PdI2, KI, and CO in MeOH.

R

R

OH

COOMe

PdI2, KI CO / MeOH 25o

OH

O

O

62–87% 1

Mousset, C., Provot, O., Hamze, A., Bignon, J., Brion, J.-D., Alami, M. T 64, 4287 (2008). Deng, Y., Li, J., Ma, S. CEJ 14, 4263 (2008). 3 Gabriele, B., Mancuso, R., Salerno, G., Plastina, P. JOC 73, 756 (2008). 2

Palladium(II) triﬂate. 1-Indenols. Coupling between o-formylarylboronic acids with alkynes leads to indenols. The catalyst system includes Pd(OTf)2 . 2H2O and Me4-SEGPHOS ligand.1

R

R

B(OH)2

Pd(OTf) 2

+ CHO

R'

O O O

1

R'

O

Yang, M., Zhang, X., Liu, X. OL 9, 5131 (2007).

PPh2 PPh2

OH

Phase-transfer catalysts

351

Pentaﬂuoroanilinium triﬂate. Acylation.1 Silyl enol ethers and ketene silyl acetals are acylated to give b-keto carbonyl compounds with C6F5NH3OTf as catalyst. 1

Iida, A., Osada, J., Nagase, R., Misaki, T., Tanabe, Y. OL 9, 1859 (2007).

Pentamethylcyclopentadienylbis(vinyltrimethylsilane)cobalt. Hydrogen transfer.1 Cyclic amines are dehydrogenated via hydrogen transfer to the N-vinyldimethylsilyl group, attached by heating with the title catalyst. SiMe3 Cp*Co

2

N Si

N Si

80

o

1

Bolig, A.D., Brookhart, M. JACS 129, 14544 (2007).

Perﬂuorooctanesulfonic acid. Pictet–Spengler reaction.1 Serving as both a Bronsted acid and a surfactant the sulfonic acid enables Pictet –Spengler reaction in water or aqueous hexaﬂuoroisopropanol. 1

Saito, A., Numaguchi, J., Hanzawa, Y. TL 48, 835 (2007).

Perrhenic acid. Phosphorylation.1 Alcohols are phosphorylated by phosphoric acid on heating with ReO3(OH) and Bu2NH in NMP. 1

Sakakura, A., Katsukawa, M., Ishihara, K. ACIE 46, 1423 (2007).

Phase-transfer catalysts. Robust catalyst. Didecyldimethylammonium bromide is proposed as a universal potent PTC because it is stable to heat and alkali.1 Dehydrochlorination. The ready availability of b-chloro enamides makes them useful precursors of ynamides. Thus phase-transfer conditions (e.g., with Bu4NHSO4, 50% NaOH in PhMe) are generally applied to complete the preparation.2 Bn 50% NaOH

N Ts

Bu4NHSO4

Cl

R

Bn N Ts

PhMe

R = Bu 65%

R

352

Phenyliodine(III) bis(triﬂuoroacetate)

Isomerization.3 Alkenylidenecyclopropanes can be converted into the conjugated alkenylcyclopropenes by heating with Bu4NHSO4 and NaOH in toluene at 608. Alkylation.4 Fischer carbene complexes can be allylated at room temperature under phase transfer conditions.

OMe

45% KOH

+ Cr(CO)5

Bu4NBr / CH2Cl2

OMe

Br

Cr(CO)5 88%

1

Chidambaram, M., Sonavane, S.U., de la Zerda, J., Sasson, Y. T 63, 7696 (2007). Couty, S., Barbazanges, M., Meyer, C., Cossy, J. SL 905 (2005). 3 Shao, L.-X., Zhang, Y.-P., Qi, M.-H., Shi, M. OL 9, 117 (2007). 4 Menon, S., Sinha-Mahapatra, D., Herndon, J.W. T 63, 8788 (2007). 2

Phenyliodine(III) bis(triﬂuoroacetate). Resin oxidant. By mixing PhI(OCOCF3)2 with a resin containing trimethylammonium iodide subunits, iodolysis occurs and the resin becomes attached to triﬂuoroacetoxyiodate anions. The new resin is capable of mediating the oxidative hydrolysis of dithioacetals.1 Addition reactions. Electron-rich styrenes undergo twofold addition to give arylacetaldehyde 1,1-bis(triﬂuoroacetates).2 The phenyliodonio intermediates are subject to displacement, for example by N-acylhydrazines.3 PhI(OCOCF3)2

MeO

CH2Cl2

CH(OCOCF3)2 MeO

O O

N NHAc PhI(OCOCF3)2

O

Ac N N

OCOCF3

CHCl3

+

O

Ar

Ar

4-Alkynoic acids and amides cyclize to provide g-acyl-g-butyrolactones and lactams, respectively.4 But PhI(OCOCF3)2 plays a different role when the substrates are changed to 3-alkenoic acids (with the presence of PhSeSePh in 5 mol%).5

Phenyliodine(III) bis(triﬂuoroacetate)

R

PhI(OCOCF3)2

COXH

R

CF3CH2OH

X

353

O

O

0o

X = O, NR' R R

COOH

PhI(OCOCF3)2

O

PhSeSePh MeCN 23o

O

Oxidation of aromatic compounds. The completion of a synthesis of frondosin-C relied on the conversion of the phenolic moiety to a 4-hydroxy-2,5-cyclohexadienone by PhI(OCOCF3)2.6 The transformation cannot be done with PhI(OAc)2

PhI(OCOCF3)2

HO

MeCN–H2O

O

(4 : 1) 0o

OH

Naphthalene is oxidized by PhI(OCOCF3)2, becoming an arylating agent for mesitylene and other polymethylbenzenes in the presence of BF3 . OEt2.7 The highly reactive p-bond of an indole nucleus can be protected by the addition of an ethylenedioxy unit. The adducts are formed in a reaction with ethanediol in the presence of PhI(OCOCF3)2. Reversion of the process is accomplished by NaBH3CN.8 Oxidative cleavage and rearrangement. Epoxy carbinols of the oxapropellane-type are driven by ring strain to undergo hydrative devolution. Formation of phenyliodoniodioxolanes provokes an intramolecular redox decomposition and further transformations.9 OH PhI(OCOCF3)2

O

O O

OH

MeCN–H2O (4 : 1) 0o

1

Luiken, S., Kirschning, A. JOC 73, 2018 (2008). Tellitu, I., Dominguez, E. T 64, 2465 (2008). 3 Murata, K., Tsukamoto, M., Sakamoto, T., Saito, S., Kikugawa, Y. S 32 (2008). 4 Tellitu, I., Serna, S., Herrero, M.T., Moreno, L., Dominguez, E., SanMartin, R. JOC 72, 1526 (2007). 5 Browne, D.M., Niyomura, O., Wirth, T. OL 9, 3169 (2007). 6 Li, X., Kyne, R.E., Ovaska, T.V. T 63, 1899 (2007). 7 Dohi, T., Ito, M., Morimoto, K., Iwata, M., Kita, Y. ACIE 47, 1301 (2008). 2

354

Phenyliodine(III) diacetate

8

Takayama, H., Misawa, K., Okada, N., Ishikawa, H., Kitajima, M., Hatori, Y., Murayama, T., Wongseripipatana, S., Tashima, K., Matsumoto, K., Horie, S. OL 8, 5705 (2006). 9 Fujioka, H., Matsuda, S., Horai, M., Fujii, E., Morishita, M., Nishiguchi, N., Hata, K., Kita, Y. CEJ 13, 5238 (2007).

Phenyliodine(III) diacetate. Generation of electrophilic halogen. The title reagent has found use in oxidation of KBr to initiate cyclization of homoallylic sulfonamides.1 The use of the p-anisyl congener to oxidize powdered KBr for benzylic bromination is also realized. 4-Arylbutanoic acids are converted into g-aryl-g-butyrolactones by this method.2 Oxidative functionalization. p-Substituted phenols are oxidized and trapped by various nucleophiles. For example, reaction carried out in the presence of MeCN furnishes 4-acetamino-2,5-cyclohexadienones.3 N-Tosylimines of 4-ﬂuoro-2,5-cyclohexadienones are obtained when HF-pyridine is added to the corresponding reaction of N-tosylanilines.4 Hydroxylation of 4-arylphenols (in aqueous MeCN) proceeds much better from the corresponding trimethylsilyl ethers.5

NHTs

NTs PhI(OAc)2 HF–Py

R

R

F

Using an allylsilane as trapping agent for the reactive species derived from phenols, formation of 2-silylmethyldihydrobenzofurans is observed.6

OH

SiMe3

+ R

O

PhI(OAc)2 CF3CH2OH

SiMe3

R

Thioureas suffer desulfurization and N-acetylation on treatment with PhI(OAc)2. Acetylation occurs at the nitrogen atom with a lower pKa.7

S PhN H

O

PhI(OAc)2

NHR

MeCN

PhN Ac

NHR

Phenyliodine(III) diacetate

355

Oxidation of guanidines can lead to cyclization, i.e., functionalization at an unactivated carbon atom.8 Such a reaction is of obvious synthetic interest.

Br O N O S

H N

Br

N

Br

Cl3C

MgO

N

H N

PhI(OAc)2

H2N H

H N

HN

w

N N

O

Br

O

30 –38%

In the last step of a dibromophakellstatin synthesis,9 PhI(OAc)2 serves well to effect closing of the central piperazinone moiety in what is actually a vicinal diamination reaction. [Pd(OAc)2 – DMSO can also be employed.] Br

O

H N

N

PhI(OAc)2

O

Br

Br H N

O

N HN

HN

Br

Na2CO3

HN

N

CF3CH2OH

O

97%

vic-Dioxygenation of double bonds has been carried out at room temperature with PhI(OAc)2 and catalytic amounts of the (dppp)Pd(2H2O)(OTf)2 complex.10

Ph

PhI(OAc)2 (dppp)Pd(OTf )2(H2O)2 HOAc, H2O (3 equiv); Ac2O

OH

Ph OH OAc 83% OAc

PhI(OAc)2 (dppp)Pd(OTf)2(H2O)2 HOAc, H2O (3 equiv); Ac2O

O 80%

3-Butenols are converted into 3-phthalimidotetrahydrofurans in an oxidative cyclization process in the presence of phthalimide.11 The oxidation is mediated by PhI(OAc)2 while a combination of Pd(OAc)2 and AgBF4 provides the necessary catalyst.

356

Phenyliodine(III) diacetate – copper salts

O

O +

HO R

PhI(OAc)2

N

Pd(OAc)2

HN O

AgBF4 MeCN 60o

O

O R

a-Substituted benzylidenecyclopropanes and cyclobutanes undergo ring-enlarging rearrangement on reaction with the nitrenoid generated from N-aminophthalimide [with PhI(OAc)2] to provide homologous cycloalkanone hydrazones.12 Trapping of oxidized phenols by reaction with furan features a formal [3 þ 2]cycloaddition.13 OH

PhI(OAc)2

+ O

O H

CF3CH2OH

H O

For cleavage of 1,2-diols, a polymer-linked aryliodine(III) diacetate has been developed.14 1

Fan, R., Wen, F., Qin, L., Pu, D., Wang, B. TL 48, 7444 (2007). Dohi, T., Takenaga, N., Goto, A., Maruyama, A., Kita, Y. OL 9, 3129 (2007). 3 Liang, H., Ciufolini, M.A. JOC 73, 4299 (2008). 4 Basset, L., Martin-Mingot, A., Jouannetaud, M.-P., Jacquesy, J.-C. TL 49, 1551 (2008). 5 Felpin, F.-X. TL 48, 409 (2007). 6 Berard, D., Racicot, L., Sabot, C., Canesi, S. SL 1076 (2008). 7 Singh, C.B., Ghosh, H., Murru, S., Patel, B.K. JOC 73, 2924 (2008). 8 Wang, S., Romo, D. ACIE 47, 1284 (2008). 9 Lu, J., Tan, X., Chen, C. JACS 129, 7768 (2007). 10 Li, Y., Song, D., Dong, V.M. JACS 130, 2962 (2008). 11 Desai, L.V., Sanford, M.S. ACIE 46, 5737 (2007). 12 Liang, Y., Jiao, L., Wang, Y., Chen, Y., Ma, L., Xu, J., Zhang, S., Yu, Z.-X. OL 8, 5877 (2006). 13 Berard, D., Jean, A., Canesi, S. TL 48, 8238 (2007). 14 Chen, F.-E., Xie, B., Zhang, P., Zhao, J.-F., Wang, H., Zhao, L. SL 619 (2007). 2

Phenyliodine(III) diacetate – copper salts. Iodoalkynes. Iodination agent for 1-alkynes is generated from a mixture of PhI(OAc)2 and KI, and the iodination is catalyzed by CuI while the liberated proton is removed by Et3N.1 Homocoupling of 1-alkynes is achieved. Dialkynylpalladium intermediates are formed from alkynes in the presence of PdCl2, CuI, Ph3P, and Et3N, and the Pd(0) species liberated on reductive elimination is reoxidized with PhI(OAc)2 in situ.2 CZH Functionalization. Allylic and benzylic positions are oxygenated by reaction with N-hydroxyphthalimide, and the reaction is realized with the assistance of PhI(OAc)2 –CuCl.3

Phenyliodine(III) diacetate – iodine

357

Ar Ar

HO N

O

O N

PhI(OAc)2

+

CuCl MeCN 70o

O

O

O

Cyclic ethers are also activated at an a-position on treatment with PhI(OAc)2 –Cu(OTf)2 and tosylamination can be accomplished by introducing TsNH2 into the reaction media.4 Three-membered rings. The combination of PhI(OAc)2 and Cu(II) triﬂuoroacetylacetonate is particularly useful for generating nitrenoid from 6-methylpyridine-2sulfonamide.5 A cyclopropanation agent is created from MeNO2 by PhI(OAc)2 and Rh2(esp)4.6 1

Yan, J., Li, J., Cheng, D. SL 2442 (2007). Yan, J., Lin, F., Yang, Z. S 1301 (2007). 3 Lee, J.M., Park, E.J., Cho, S.H., Chang, S. JACS 130, 7824 (2008). 4 He, L., Yu, J., Zhang, J., Yu, X.-Q. OL 9, 2277 (2007). 5 Han, H., Park, S.B., Kim, S.K., Chang, S. JOC 73, 2862 (2008). 6 Bonge, H.T., Hansen, T. SL 55 (2007). 2

Phenyliodine(III) diacetate – iodine. Ring cleavage. Several oxidants can cleave lactols at the CaZCb bond, and the PhI(OAc)2 –I2 pair is useful for attaching an iodine atom to Cb in the process. From bicyclic lactols such as those prepared from alkylation of cycloalkanones with epoxides as substrates iodolactones are obtained.1 O

OH O

PhI(OAc)2 – I2

R

CH2Cl2

O

0o

R I

Oxidation of amines. Secondary alkyl amines undergo oxidative cyclization to give pyrrolidines. However, N-tosylbenzylamines can only be dehydrogenated.2

NH R

R'

PhI(OAc)2 –I2

N R

ClCH2CH2Cl 25o

R'

PhI(OAc)2 –I2

Ar 1

NHTs

ClCH2CH2Cl 25o

Maio, W.A., Sinishtaj, S., Posner, G.H. OL 9, 2673 (2007). Fan, R., Pu, D., Wen, F., Wu, J. JOC 72, 8994 (2007).

2

Ar

NTs

358

Phenyliodine(III) dichloride

Phenyliodine(III) dichloride. Oxidation. The title reagent is available from chlorination of PhI with NaClOn in hydrochloric acid. It can be used in conjunction with TEMPO to oxidize alcohols.1 1

Zhao, X.-F., Zhang, C. S 551 (2007).

Phenylphosphinic acid. Ugi reaction.1 A new catalyst for the three-component condensation is PhPO(OH)H. NHAr Ph-P(=O)(OH)H

PhCHO + ArNH2

+

t-BuNC

Ph

H N

O

1

Pan, S.C., List, B. ACIE 47, 3622 (2008).

Phenylselenium triﬂate. Glycosylation.1 Glycosyl 4-pentenoates are activated by PhSeOTf and smooth glycosylation is achieved (2,4,6-tri-t-butylpyrimidine is used as base). 1

Choi, T.J., Baek, J.Y., Jeon, H.B., Kim, K.S. TL 47, 9191 (2006).

4-Phenyl-1,2,4-triazoline-3,5-dione. Disulﬁdes.1 The title heterocycle rapidly oxidizes thiols at room temperature. 1

Christoforou, A., Nicolaou, G., Elemes, Y. TL 47, 9211 (2006).

Pinacolatoboryl azide. CZH insertion.1 Hydrocarbons such as cyclohexane are functionalized (converted to amines) in good yields by co-irradiation with the title reagent to afford B-aminoboryl pinacolates. 1

Bettinger, H.F., Fiethaus, M., Bornemann, H., Oppel, I.M. ACIE 47, 4744 (2008).

Piperidine. Condensation.1 A remarkable solvent dependence of the product geometry in the condensation of aldehydes with nitroalkanes has been unraveled.

Platinum and complexes

359

R'

CH2Cl2 25o NH

R' RCHO

+ NO2

R

NO2

R

R'

4A-MS PhMe 110o

NO2

1

Fioravanti, S., Pellacani, L., Tardella, P.A., Vergari, M. C. OL 10, 1449 (2008).

Platinum and complexes. Hydrogenation and dehydrogenation. Supported on carbon in a nanoﬁber form Pt catalyzes selective hydrogenation of nitroarenes to give arylamines in the presence of many other functional groups.1 Diphenylamine and 2-aminobiphenyl are dehydrogenated to furnish carbazole on heating with Pt/C and some water at 2508.2 It is thought that [Pt-H][OH] are formed. Under similar conditions Pd/C is ineffectual. The Pt-catalyzed hydrogenation of the pyridine nucleus in HOAc is facilitated by microwave.3 Addition reactions. Hydrodisilanes generate Pt-coordinated silylenes on exposure to (cod)PtCl2. These silylenoids conjugatively add to enones,4 except those containing a (Z)-methyl substituent at the b-carbon (in such cases the major products are 1-oxa-2-sila5-cyclohexenes).5 O R

O R

O Ph

Si

Me3Si–Si(Me2)H

R'

(cod)PtCl2

R

(cod)PtCl2

R + R Si Si H 3 Ph R

R' Si

Me3Si–Si(Me2)H

R'

O

O

R

R' R R Si

(cod)PtCl2 PhMe 40

o

Ph

O Ph

R = Me 65%

A synthesis of (E)-1-triorganosilyl-1-alkenes by hydrosilylation of 1-alkynes can be accomplished in the presence of a carbene-Pt complex in which the metal is also ligated to the two double bonds of diallyl ether.6 Allylation. The (cod)PtCl2 complex associated with bis(o-diphenylphosphinophenyl) ether effects monoallylation of amines by allylic alcohols.7

360

Platinum(II) acetylacetonate

1

Takasaki, M., Motoyama, Y., Higashi, K., Yoon, S.-H., Mochida, I., Nagashima, H. OL 10, 1601 (2008). 2 Yamamoto, M., Matsubara, S. CL 36, 172 (2007). 3 Piras, L., Genesio, E., Ghiron, C., Taddei, M. SL 1125 (2008). 4 Okamoto, K., Hayashi, T. CL 37, 108 (2008). 5 Okamoto, K., Hayashi, T. OL 9, 5067 (2007). 6 Berthon-Gelloz, G., Schumers, J.-M., De Bo, G., Marko, I.E. JOC 73, 4190 (2008). 7 Utsunomiya, M., Miyamoto, Y., Ipposhi, J., Ohshima, T., Mashima, K. OL 9, 3371 (2007).

Platinum(II) acetylacetonate. Addition reactions.1 Addition of borylsilanes to the triple bond of a conjugated enyne, catalyzed by Pt(acac)2, is subject to substrate control in that the steric bulk of the terminal substituent exerts an important effect.

Dibal-H Cy3PO

R

Ph Si C

O

RL

B O

R' +

Pt(acac)2

O

PhMe

B Si Ph

RS

O

O

B

Dibal-H

O

(EtO)3P

Si Ph

R'

1

Lu¨ken, C., Moberg, C. OL 10, 2505 (2008).

Platinum(II) chloride. Addition reactions. Hydrosilanes add to ethynylarenes regioselectively and stereoselectively, when catalyzed by PtCl2 in the presence of X-Phos.1

PtCl2

Ar

+

R3SiH

Ar SiR3

Cy2P

Indoles undergo tetrahydrofuranylation (at C-3) when mixed with 3-alkynols and PtCl2.2

Platinum(II) chloride

R

R

361

O

PtCl2 THF 25o

N R'

N R'

HO

75–93%

Cyclization. Activation of an alkyne by Pt(II) often initiates nucleophilic attack, and with a well-juxtaposed double bond cyclization ensues. The concluding act may then involve addition of an alkoxy unit,3 or neutralization of the positive charge with a hydride source such as a hydrosilane.4 OR H

PtCl2 ROH

H COOMe MeOOC

H MeOOC

H

PtCl2 PhMe 80

H HO

COOMe

O

o

OH

H OH

PtCl2 Et3SiH

N R

BF3 . OEt 2

N R

R, electron-withdrawing

The deprotonation option is also available.5,6 O

O

RN

RN PtCl2 PhMe 90o

H TsN

TsN PtCl2 PhMe

NBoc MeOOC

O

MeOOC

N H Boc 50%

O

362

Platinum(II) chloride

On treatment with PtCl2 under CO in toluene o-alkynylaryl alkoxymethyl ethers cyclize to afford benzofurans, by transfer of the alkocymethyl group to C-3.7 Cyclization that eventualy places the resulting double bond endocyclic also occurs, as in the annulation of indoles8 and the formation of spirocyclic furanones and pyrrolones which involves a rearrangement process.9 R" O

O

O R"

PtCl2 / CO

O

PhMe 80o

R'

N R

N R

H

R'

R O

O

PtCl2

OH

PhMe 80–100°

X

R

X = O (no additive) X = NR' (R'NH2 added)

Rearrangement precedes cyclization of a-arylpropargyl acetates to provide 2-acetoxyindenes.10 R

OAc

Ar

R PtCl2 PhMe 50o

R'

OAc

a-(o-Allylaminoaryl)propargylic ethers and acetates are converted to 2-(3-butenyl)3-oxyindoles. A [3,3]sigmatropic rearrangement takes place after nucleophilic attack on the Pt-activated triple bond by the nitrogen atom.11 OR

OR PtCl2

N R'

PhMe 25o

N R'

R = Me, Ac

a-Allylpropargyl ethers undergo cyclization to give bicyclo[3.1.0]hex-2-enyl ethers,12 N-(o-alkynyl)lactams are transformed into indoles.13 The net results are equivalent to insertion of alkylidenecarbenes into double and single bonds.

Platinum(II) chloride

OTBS

363

PtCl2

OTBS

PhMe 80o

68%

N

PtCl2 / O2

O

N

ClCH2CH2Cl

O R

R

o-Diynylarenes aromatized with participation of the nucleophile appended on the chain extending from one of the triple bonds, naphthannulated heterocycles are thereby created.14 A more convoluted cyclization is that represented by a-enynyl o-alkenylbenzyl alcohols.15 HX

R R X PtCl2 / CO 100o

R

R

R' PtCl2 THF 25o

OH R'

Transformation of 1,2,4-alkatrienes into cyclopentadienes is catalyzed by PtCl2 at room temperature.16 Cycloisomerization to break up an acetal unit and re-add the O/C bonding partners to a conjugated triple bond has been observed.17

R

OR'

COOR"

R

PtCl2

O

PhMe

OR'

COOR" OR'

+ R R

COOR" O

R R

O

a-(2-Aziridinyl)propargyl acetates are subject to isomerization, which is instigated by the shift of the ester unit. Dihydropyridines are formed.18 OAc

OAc

PtCl2

NTs Ph

PhMe 100o

Ph

N Ts

364

Platinum(II) chloride

Cycloaddition. Many types of cycloaddition reactions catalyzed by PtCl2 have been discovered. Platinized carbonyl ylides formed in situ from 4-alkynones are intercepted by electron-rich alkenes.19 R

R O

R O

PtCl2

R' R'

R'

R"

OBu

[Pt]

R"

O R"

OBu

Intramolecular cycloaddition involving conjugated diene and allene units leads to bicyclic products that contain a 1,4-cycloheptadiene nucleus.20 [6 þ 2]Cycloaddition of some cycloheptatrienes appended with a sidechain containing a triple bond occurs at room temperature, with PtCl2 to promote it. At higher temperature, the formal [6 þ 1]cycloadducts are formed.21 R R

R

C

R

PtCl2

Z

PhMe

O

Z

110o

O

PtCl2

O

H

PhMe

25o

85o

An intramolecular alkenylation is the key step for a synthesis of the zwitterionic dihetero analogue of pyrene in which the two internal carbon atoms are replaced by N and B atoms.22

N B

PtCl2 PhMe 100o

N B

Isomerization. 3-Acyloxyalkynyl ethers undergo rearrangement to afford 2-alkylidene-3-oxoalkanoates. Metal salts that induce the reaction may affect the stereoselectivity differently.23

Platinum(II) chloride – silver salts

365

R' O

O O

O

COOEt

R'

+

R

R

R

OEt

COOEt

R'

70–10 : 30–0

PtCl2 (MeCN)4CuX

10–0 : 90–100

1

Hamze, A., Provot, O., Brion, J.-D., Alami, M. TL 49, 2429 (2008). Bhuvaneswari, S., Jeganmohan, M., Cheng, C.-H. CEJ 13, 8285 (2007). 3 Yeh, M.-C.P., Tsao, W.-C., Cheng, S.-T. JOC 73, 2902 (2008). 4 Harrison, T.J., Patrick, B.O., Dake, G.R. OL 9, 367 (2007). 5 Kozak, J.A., Dake, G.R. ACIE 47, 4221 (2008). 6 Deng, H., Yang, X., Tong, Z., Li, Z., Zhai, H. OL 10, 1791 (2008). 7 Fu¨rstner, A., Heilmann, E. K., Davies, P.W. ACIE 46, 4760 (2007). 8 Zhang, G., Catalano, V.J., Zhang, L. JACS 129, 11358 (2007). 9 Binder, J.T., Crone, B., Kirsch, S.F., Liebert, C., Menz, H. EJOC 1636 (2007). 10 Nakanishi, Y., Miki, K., Ohe, K. T 63, 12138 (2007). 11 Cariou, K., Ronan, B., Mignani, S., Fensterbank, L., Malacria, M. ACIE 46, 1881 (2007). 12 Blaszykowski, C., Harrak, Y., Brancour, C., Nakama, K., Dhimane, A.L., Fensterbank, L., Malacria, M. S 2037 (2007). 13 Li, G., Huang, X., Zhang, L. ACIE 47, 346 (2008). 14 Taduri, B.P., Odedra, A., Lung, C.-Y., Liu, R.-S. S 2050 (2007). 15 Abu Sohel, S.M., Lin, S.-H., Liu, R.-S. SL 745 (2008). 16 Funami, H., Kusama, H., Iwasawa, N. ACIE 46, 909 (2007). 17 Nakamura, I., Chan, C.S., Araki, T., Terada, M., Yamamoto, Y. OL 10, 309 (2008). 18 Motamed, M., Bunnelle, E.M., Singaram, S.W., Sarpong, R. OL 9, 2167 (2007). 19 Kusama, H., Ishida, K., Funami, H., Iwasawa, N. ACIE 47, 4903 (2008). 20 Trillo, B., Lopez, F., Gulias, M., Castedo, L., Mascarenas, J.L. ACIE 47, 951 (2008). 21 Tenaglia, A., Gaillard, S. ACIE 47, 2454 (2008). 22 Bosdet, M.J.D., Piers, W.E., Sorensen, T.S., Parvez, M. ACIE 46, 4940 (2007). 23 Barluenga, J., Riesgo, L., Vicente, R., Lopez, L.A., Tomas, M. JACS 129, 7772 (2007). 2

Platinum(II) chloride – silver salts. Addition reaction. Hydroarylation of 2-alkynoic acids and esters occur on their treatment with ArH and PtCl2 – AgOTf in TFA at room temperature.1

R

COOR' + ArH

PtCl2 AgOTf CF3COOH 25o

R Ar

COOR'

Tetrahydropyrans. Reductive incorporation of aldehydes into a tetrahydropyran ring by combining with certain unsaturated alcohols is mediated by the PtCl2 –AgOTf couple.2

366

Platinum(II) iodide

O

OH +

RCHO

R

AgOTf PhMe 100o

1

Oyamada, J., Kitamura, T. T 63, 12754 (2007). Miura, K., Horiike, M., Inoue, G., Ichikawa, J., Hosomi, A. CL 37, 270 (2008).

2

Platinum(II) iodide. Indolizines. Cycloisomerization of g-(2-pyridyl)propargylic esters catalyzed by PtI2 –Ph3P is found to be affected by substituents at the a-position and the acyl group.1 Perhaps formation of two different types of products is determined by the degree of loosening of the propargyloxy bond.1 OCOR OCOR

R' PtI2

N

PhH 100

COOR

N

(C6F5)3P

N R'

o

R: e-withdrawing R': e-donating

R' R: e-donating R': e-withdrawing

1

Hardin, A.R., Sarpong, R. OL 9, 4547 (2007).

Poly(methylhydrosiloxane), PMHS. Reductive transformations. Reduction of aldehydes to primary alcohols is accomplished by reduction with PMHS which is catalyzed by Fe(OAc)2 –Cy3P.1 PMHS also ﬁnds use in the reductive amination of b-hydroxy ketones to afford syn-1,3amino alcohols using (i-PrO)4Ti as a catalyst.2 With Pd(OH)2/C as catalyst a mixture of RCN and ArNX2 (X ¼ H or O) is converted by PMHS in ethanol to RCH2NHAr.3 The stabilized copper hydride species 1 is obtained by mixing PMHS with Cu(OAc)2 . 2H2O in t-BuOH and toluene in the presence of 1,2-bis(diphenylphosphino)benzene at room temperature.4 It can be used in lieu of the Stryker reagent.

Ph P

Ph CuH

P Ph

(1)

Ph

Potassium t-butoxide

367

Alternatively, carbene-complexed copper hydride species is involved in the transformation of alkynyl epoxides to allenyl carbinols using CuI, t-BuONa, PMHS and a imidazolium salt.5

PMHS

O R'

CuCl–t-BuONa

R

H

C

O

O N

R

N

R' OH

TfO

Hydroiodination. A combination of PMHS and iodine is useful for hydroiodination of alkenes and alkynes, in the Markovnikov sense, at room temperature in CHCl3.6 1

Shaikh, N.S., Junge, K., Beller, M. OL 9, 5429 (2007). Menche, D., Arikan, F., Li, J., Rudolph, S. OL 9, 267 (2007). 3 Reddy, C.R., Vijeender, K., Bhusan, P.B., Madhavi, P.P., Chandrasekhar, S. TL 48, 2765 (2007). 4 Baker, B.A., Boskovic, Z.V., Lipshutz, B.H. OL 10, 289 (2008). 5 Deutsch, D., Lipshutz, B.H., Krause, N. ACIE 46, 1650 (2007). 6 Das, B., Srinivas, Y., Holla, H., Narender, R. CL 36, 800 (2007). 2

Potassium t-butoxide. Vinylation. Condensation of aldehydes with chloromethyl methyl sulfones results in the formation of 1-alken-3-ols. This late stage of this interesting reaction resembles the Payne rearrangement and it is terminated by extrusion of SO2.1

R RCHO

+

K

t-BuOK

Cl

O

SO2Me O

R

OH

S CH2 O

Elimination. Enamine N-oxides are synthesized from b-chloroalkylamines in two steps. N-Oxidation by MCPBA and dehydrochlorination with t-BuOK.2

Aldol reaction. Cyclization of a keto ester effected by t-BuOK in reasonably good yield and stereoselectivity constitutes a key step toward completion of a synthesis of (-)salinosporamide-A.3

368

Potassium ﬂuoride

O O

O

t-BuOK

N

N

THF

COOMe

O

O

COOMe OH 64%

1

Makosza, M., Urbanska, N., Chesnokov, A.A. TL 44, 1473 (2003). Bernier, D., Blake, A.J., Woodward, S. JOC 73, 4229 (2008). 3 Ling, T., Macherla, V.R., Manam, R.R., McArthur, K.A., Potts, B.C.M. OL 9, 2289 (2007). 2

Potassium ﬂuoride. N-Allylation. To achieve monoallylation of arylamines in MeCN a useful base system is KF on Celite.1 Dialkyl ﬂuorophosphates. Oxidative ﬂuorination of dialkyl phosphinites occurs on heating with KF and Cl3CCN.2 Carbamates. On Hofmann rearrangement of an amide RCONH2 the treatment with KF/Al2O3 in MeOH leads to RNHCOOMe.3 Deformylation. Arylamines are liberated from formanilides by mixing with KF/ Al2O3 and microwave irradiation.4 1

Pace, V., Martinez, F., Fernandez, M., Sinisterra, J.V., Alcantara, A.R. OL 9, 2661 (2007). Gupta, A.K., Acharya, J., Pardasani, D., Dubey, D.K. TL 49, 2232 (2008). 3 Gogoi, P., Konwar, D. TL 48, 531 (2007). 4 Ge, Y., Hu, L. TL 48, 4585 (2007). 2

Potassium monoperoxysulfate, Oxonew. Amides. A new protocol for making ArCONHAr 0 from ArCHO and Ar 0 NH2 is by ball-milling the mixture with Oxone.1 Epoxidation. N-(Bis[diisopropylamino]methoxyphosphonio)oxaziridines 1 are valuable oxygen donors. They are accessible by oxgen transfer from Oxone to the iminium salts. Actually the imine can be used in catalytic quantities for the oxygen transfer reaction.2

Ar O

N N P MeO N

(1)

TfO

Potassium permanganate

369

Quinones. Oxidation of p-methoxyphenols by Oxone is catalyzed by p-iodophenoxyacetic acid.3 1

Gao, J., Wang, G.-W. JOC 73, 2955 (2008). Prieur, D., El Kazzi, A., Kato, T., Gornitzka, H., Baceiredo, A. OL 10, 2291 (2008). 3 Yakura, T., Konishi, T. SL 765 (2007). 2

Potassium osmate. Oxidative cyclization.1 The scope of oxidative cyclization by K2OsO2(OH)4 in forming 2-hydroxymethylpyrrolidines from aminoalkene derivatives is expanded by adding pyridine-N-oxide and citric acid to the reaction medium that contains TFA, acetone and water.

OH

(KO) 2OsO2(OH)2 Py-O, CF 3COOH

NHNs

N Ns

HO

Me2CO, H2O

OH

Aminohydroxylation.2 Functionalization of the double bond of an allylic alcohol by intramolecular cis-aminohydroxylation is attended by dramatic improvement by derivatizing the alcohols into N-hydroxycarbamates and thence the N-pentaﬂuorobenzoyloxy carbamates.

O O

O NHOCOC6F5

H

O NH

(KO) 2OsO2(OH)2

H OH

t-BuOH– H2O (3 : 1)

98%

1

Donohoe, T.J., Wheelhouse, K.M.P., Lindsay-Scott, P.J., Glossop, P.A., Nash, I.A., Parker, J.S. ACIE 47, 2872 (2008). 2 Donohoe, T.J., Bataille, C.J.R., Gattrelle, W., Kloesges, J., Rossignol, E. OL 9, 1725 (2007).

Potassium permanganate. a-Acyloxylation. Heating 2-cycloalkenones (including indanone and a-tetralone) with a carboxylic acid and KMnO4 in benzene furnishes the a0 -acyloxy derivatives.1

370

Potassium tetrachloroaurate

O

O +

RCOOH

OCOR

KMnO4 PhH

O

O + HOAc

KMnO4 PhH

MeO

OAc MeO 75%

1

Demir, A.S., Findik, H. T 64, 6196 (2008).

Potassium tetrachloroaurate. Allenes. 1,3-Chirality transfer in the hydrodeamination of N-propargyl(S)-prolinols which occurs on treatment with KAuCl4 in MeCN.1

N

OH KAuCl 4 MeCN 40o

R H

R'

R

H C

H

R'

1

Lo, V.K.-Y., Wong, M.-K., Che, C.-M. OL 10, 517 (2008).

o-(Prenyloxymethyl)benzoic acid. Hydroxyl protection. By using the title reagent in the Mitsunobu reaction alcohols are protected. The prenyl group of the derived esters is removable by DDQ and subsequent addition of Yb(OTf)3 promotes lactonization to liberate the alcohols.1 1

Vate`le, J.-M. T 63, 10921 (2007).

(S)-Proline. Aldol reaction. Aldol reaction catalyzed by proline and derivatives has been reviewed.1 A ball-mill operation on cycloalkanones, ArCHO with (S)-proline leads to predominantly anti-aldol products.2 The aldol reaction between 4-tetrahydrothiapyrone with the racemic 3-aldehyde based on the same heterocycle shows excellent enantiotopic groupselectivity and thence manifesting dynamic kinetic resolution.3

(S)-Proline

371

O

OHC

O

O

OHC

O

O

O

COOH

N H

S

S

HO

O

O

S

S

S

56% (>98% ee)

(S )-Proline is effective in mediating an asymmetric transannular aldol reaction.4

O

O

F

H

N COOH H

OH O

84%

H (+)-hirsutene

The anti-selective aldol reaction between cyclohexanone and ArCHO reaches .99% ee if it is conducted in the presence of trans-4-(4-t-butylphenoxy)-L-proline and sulfated b-cyclodextrin in water at room temperature.5 Another catalyst is cis-4-(1-adamantanecarboxamido)-(S)-proline (1) in conjunction with b-cyclodextrin.6

O HN COOH N H

(1) It appears best to carry out aldol reaction between two aldehydes in dry conditions, and between a ketone and an aldehyde under wet conditions.7 The use of proline to accomplish the Friedla¨nder reaction to produce 2-substituted 4-triﬂuoromethylquinolines takes advantage of its efﬁciency rather than chiroptical results (for there is none).8

Miscellaneous reactions. The starting point of a practical route to b2-amino acids is the proline-catalyzed Mannich reaction of aldehydes with a chiral iminium salt derived from N-benzyl-N-(a-phenethyl)amine.9 Condensation of aldehydes with N-Boc imines furnishes mainly syn-adducts.10,11

372

(S)-Proline

OHC

+

N Bn

R

Ph

L-Pro

OHC R

N H

Ph

Asymmetric Michael reactions have been conducted with assistance of C2-symmetric malonamides derived from (S)-proline esters.12 2-Methyl-3,4,5,6-tetrahydropyridine and 2-cyclopentenone are condensed to afford a tricyclic alcohol. The reaction starts from Michael reaction of the endocyclic enamine isomer and as the double bond shifts to the exocyclic position an intramolecular aldol reaction follows. If the imine is lithiated, the initial Michael reaction (CuBr-catalyzed) then involves the exocyclic carbon.13 OH L-Pro

N O N

+ n-BuLi CuBr

OH N

Perhaps through enamine formation from ketones proline catalyzes a Diels– Alder reaction with 1,2,4,5-tetrazines.14 Ar

Ar O N N

N N Ar

+

L-Pro DMSO 100o

N N Ar

A new use of proline is in the aromatic substitution for converting ArX to aryl cyanides (CuCN, DMF, 80o –120o).15 1

Guillena, G., Najera, C., Ramon, D.J. TA 18, 2249 (2007). Rodriguez, B., Bruckmann, A., Bolm, C. CEJ 13, 4710 (2007). 3 Ward, D.E., Jheengut, V., Akinnusi, O.T. OL 7, 1181 (2005). 4 Chandler, C.L., List, B. JACS 130, 6737 (2008). 5 Huang, J., Zhang, X., Armstrong, D.W. ACIE 46, 9073 (2007). 6 Liu, K., Ha¨ussinger, D., Woggon, W.-D. SL 2298 (2007). 7 Hayashi, Y., Aratake, S., Itoh, T., Okano, T., Sumiya, T., Shoji, M. CC 957 (2007). 8 Jiang, B. Dong, J., Jin, Y., Du, X., Xu, M. EJOC 2693 (2008). 2

(S)-Proline amides

373

9

Chi, Y., English, E.P., Pomerantz, W.C., Horne, W.S., Joyce, L.A., Alexander, L.R., Fleming, W.S., Hopkins, E.A., Gellman, S.H. JACS 129, 6050 (2007). 10 Yang, J.W., Stadler, M., List, B. ACIE 46, 609 (2007). 11 Vesely, J., Rios, R., Ibrahem, I., Cordova, A. TL 48, 421 (2007). 12 Kim, S.-J., Lee, K., Jew, S., Park, H., Jeong, B.-S. CL 37, 432 (2008). 13 Movassaghi, M., Chen, B. ACIE 46, 565 (2007). 14 Xie, H., Zu, L., Queis, H.R., Li, H., Wang, J., Wang, W. OL 10, 1923 (2008). 15 Wang, D., Kuang, L., Li, Z., Ding, K. SL 69 (2008).

(S)-Proline amides. Aldol reaction. New amides of (S)-proline and 4-substituted prolines continue to be tested for their effectiveness in promoting enantioselective aldol reactions, mainly based on the model reaction of cyclohexanone with an ArCHO. The long list of compounds includes those of N-aryl amides 1,1 2,2 and those bearing additional chiral elements such as 3 3 and 4.4 O N H

O

O2N

HN

N H

NO2

F

HN HO

O2N

Cl

(2)

(1) TBDPSO

O O N H

N H

HN

HN HN

H N

S

O

O

(4)

(3)

Derivatives of aliphatic amines are represented by 5,5 and 6,6 and 7a.7 TBSO O N H

HN HO

O R

N H

HN

R

Ph Ph

(5) R = Ph, i-Bu

HO

(6) R = Ph (7a) R = COOEt (7b) R = COOMe

R

374

(S)-Proline amides

The prolinamide 8 is synthesized from methyl cholate.8 The diamide 9 containing two prolyl residues is said to fulﬁll the demand for cross-aldol condensation of aldehydes.9 O NH

COOMe

NH

H

H H HO

H

O N H

H

O NH

OH

(9)

(8)

H N

N H

Prolinamides featuring additional chiral elements and functional groups may ﬁnd special utilities, for example to deal with more complicated substrates. There is a report of aldol reaction between a-methylthio acetone and aldehydes which relies on 7b.10 For promoting reactions of ethyl glyoxylate, the dipeptide 10 has been employed.11 AcO O N H

HN COOH

(10) (S )-Prolyl derivative of BINAMINOL (amide) shows catalytic activities for antiselective aldol reaction.12 When 1,1,1-triﬂuoro-3-alken-2-ones serve as aldol acceptors, the simple N-benzenesulfonylprolinamide plays an adequate catalytic role to guide the reaction.13 Other condensations. The tripeptide H-(R)-Pro-Pro-Asp-NH2 proves highly efﬁcient in catalyzing the Michael reaction of aldehydes with conjugated nitroalkenes.14 Biginelli reaction involves a Mannich reaction of iminium species derived from aldehydes and ureas. It is activated by N-(1-adamantyl)-4-hydroxyprolinamide (11) and 2-chloro-4-nitrobenzoic acid.15

HO O N H

HN

(11) The Ullmann ether synthesis also beneﬁts from the presence of N-methylprolinamide.16

(S)-Prolinol derivatives

375

Epoxidation. For asymmetric epoxidation of alkenes capable of H-bonding by aqueous H2O2 and N,N 0 -diisopropylcarbodiimide the proline-based tripeptide 12 plays a catalytic role by transforming the aspartyl residue into a chiral peracid.17

O H Boc N

N HN O H

HOOC

N

O

Ph

(12) 1

Sato, K., Kuriyama, M., Shimazawa, R., Morimoto, T., Kakiuchi, K., Shirai, R. TL 49, 2402 (2008). Sathapornvajana, S., Vilaivan, T. T 63, 10253 (2007). 3 Tzeng, Z.-H., Chen, H.Y., Huang, C.-T., Chen, K. TL 49, 4134 (2008). 4 Russo, A., Botta, G., Lattanzi, A. T 63, 11886 (2007). 5 Maya, V., Raj, M., Singh, V.K. OL 9, 2593 (2007). 6 He, L., Jiang, J., Tang, Z., Cui, X., Mi, A.-Q., Jiang, Y.-Z., Gong, L.-Z. TA 18, 265 (2007). 7 Zhao, J.-F., He, L., Jiang, J., Tang, Z., Cun, L.-F., Gong, L.-Z. TL 49, 3372 (2008). 8 Puleo, G.L., Iuliano, A. TA 18, 2894 (2007). 9 Xiong, Y., Wong, F., Dong, S., Liu, X., Feng, X. SL 73 (2008). 10 Xu, X.-Y., Wang, Y.-Z., Cun, L.-F., Gong, L.-Z. TA 18, 237 (2007). 11 Dodda, R., Zhao, C.-G. SL 1605 (2007). 12 Wang, C., Jiang, Y., Zhang, X., Huang, Y., Li, B., Zhang, G. TL 48, 4281 (2007). 13 Wang, X.-J., Zhao, Y., Liu, J.-T. OL 9, 1343 (2007). 14 Wiesner, M., Revell, J.D., Wennemers, H. ACIE 47, 1871 (2008). 15 Xin, J., Chang, L., Hou, Z., Shang, D., Liu, X., Feng, X. CEJ 14, 3177 (2008). 16 Liu, X., Fu, H., Jiang, Y., Zhao, Y. SL 221 (2008). 17 Berkessel, A. ACIE 47, 3677 (2008). 2

(S)-Prolinol derivatives. Aldol reaction. Over the years, relatively scanty attention has been paid to the application of prolinols to catalyze the aldol reaction, compared to the massive efforts devoted to proline and prolinamides. However, the activity of 1 has been scrutinized.1

Ar N H

Ar OH

(1A) Ar = Ph (1B) Ar = 3,5-(F 3C)2C6H3

376

(S)-Prolinol derivatives

The triethylsilyl ether of a,a-diphenylprolinol 2B induces the Michael-aldol reaction tandem that combines N-protected o-aminobenzaldehydes and 2-alkenals to form chiral 2-substituted 3-formyl-1,2-dihydroquinolines.2 X Ar N H

CHO

Ar OSiR3

(2B)

CHO

R

NHTs

CHO

N Ts

(2A) Ar = Ph, R = Me, X = H (2B) Ar = Ph, R = Et, X = H (2C) Ar = 2-Np, R = Me, X = H (3A) Ar = 3,5-(F3C)2C6H3, R = Me, X = H (3B) Ar = 3,5-(F3C)2C6H3, R = Me, X = OTBS

R

More signiﬁcant results are the multi-component condensation by way of Michael-aldol3 and Michael– Michael-aldol reaction sequences4,5 and the Michael –Baylis-Hillman tandem,6 each leading to cyclohexenes bearing multiple functional groups and stereogenic centers.

CHO

CHO

+ R

R CN

NC

CHO

(3A) PhCOOH

R

PhMe

R NC

CN

CHO R

CHO

O

(1)

+ Ar

R

Ar

CH2Cl2

CHO

CHO

R"

OHC + CHO

CHO (2A)

COOEt

PhMe

CN

R

R"

o-FC6H4COOH

COOEt R

R'

CN R'

O OH

COOR' + OHC

COOR'

(2A) PhCOOH

R

PhMe

HO

R

(S)-Prolinol derivatives

377

Michael reaction. Silyl ether 2A and the enantiomeric ent-2A have been employed in inducing the Michael reaction of N-Boc hydroxylamine7 and malonate esters,8 respectively, to enals, whereas 3A has been afﬁrmed to promote the addition of S-(2,2,2-triﬂuoroethyl) alkanethioates to enals.9 Furthermore, 3A and 3B ﬁnd use in asymmetric conjugate addition of benzaldoxime10 (products are for conversion into chiral 1,3-alkanediols) and RSH,11 also to enals. The aldehyde– quinone pair is just another combination.12 Homologous series of silyl ethers of a,a-dialkylprolinols 4 have been screened for optimal performance in catalyzing asymmetric Michael reaction of aldehydes and alkenals. There appears some variance in the matching of the chain length and the substituents on the silicon atom.13

CnH2n+1 CnH2n+1

N H

OSiR3

(4) n = !, 3, 6, 9, 12 R = Me

An intramolecular Michael reaction (catalyzed by 2C) following the oxidative dearomatization of 4-substituted phenols provides valuable octalones.14 A method involving two consecutive Michael reactions to form optically active polysubstituted cyclopentanes15 should be highly rated.

O

OH PhI(OAc)2

CHO

H

(2C) / MeOH

CHO

MeO

COOEt OHC

(2A)

+

COOEt CHO

EtOH

COOR' R'OOC

R' R'OOC

R COOR'

99% ee 95% yield

Much work has also been devoted to Michael reaction of nitroalkanes to conjugated carbonyl compounds using 2A for catalysis. However, different additives (e.g., PhCOOH,16

378

(S)-Prolinol derivatives

LiOAc17) and/or reaction conditions are involved. 1,3-Dinitropropane and especially 2-substituted homologues, react with enals to provide 2,4-dinitrocyclohexanols with up to ﬁve contiguous stereocenters and ee up to 94%.18

OH CHO

NO2 +

R

R'

NO2

(3A) DABCO CH2Cl2

NO2

R

R' NO2

The combinations of aldehydes and nitroalkenes also form chiral adducts, which are valuable precursors of g-amino acids, in the presence of 2A 19,20,21 or ent-2A.22 Prolinol TBDPS ether (without a-substituents) also mediates Michael reaction of ketones with b-nitrostyrenes.23 Mannich and related reactions. A two-step procedure gives access to amino alcohols bearing a chirality center at the a-carbon atom, the crucial step being a Mannich reaction.24 NBn2 MeO

CHO

+ R

(2A) HOAc

NBn2

LiBr, DMF; NaBH4

OH R

In hydroxylamination of aldehydes with PhNvO under the inﬂuence of 2A, external hydrogen-bond donors are not required.25 Cycloaddition reactions. Asymmetric induction in cycloaddition of enals is based on the formation of conjugated iminium salts with bulky prolinol derivatives. Reaction partners include enamides26 and cyclopentadiene.27 The Diels–Alder reaction (catalyst: 3B) is exoselective. Asymmetric aziridination of enals by N-acetoxycarbamates in the presence of 2A has been demonstrated.28 Addition to ArCHO. Synthesis of chiral secondary benzylic alcohols by addition of organometallic reagents (including Me2Zn and Ar3Bi) can be asymmetrically directed by (S)-a,a-diphenylprolinol.29 Redox reactions. Two prolinol derivatives 5 30 and 6 31 with polyﬂuorinated a-substituents have been developed for use in the CBS-type reduction. Immobilization of 6 in hydroﬂuoroether perhaps contributes to the attainment of high ee of the reduction and it facilitates recovery of the adjuvant (for reuse).

(S)-Prolinol derivatives

379

C8F17 C6F13

N H

N H HO

C6F13

HO

C8F17

(6)

(5)

The prolinol 7 assists epoxidation of enones (reagent: t-BuOOH), but good ee are obtained only with chalcones.32

BnO

N H

HO

(7) A series of bicyclic P-chiral ligands for the Rh metal has been prepared from (S)-a,adiphenylprolinol and RPCl2. Various degrees of success are seen with the derived catalysts for asymmetric hydrogenation.33 1

Hayashi, Y., Itoh, T., Aratake, S., Ishikawa, H. ACIE 47, 2082 (2008). Li, H., Wang, J., Xie, H., Zu, L., Jiang, W., Duesler, E., Wang, W. OL 9, 965 (2007). 3 Hong, B.-C., Nimje, R.Y., Sadani, A.A., Liao, J.-H. OL 10, 2345 (2008). 4 Carlone, A., Cabrera, S., Marigo, M., Jorgensen, K.A. ACIE 46, 1101 (2007). 5 Penon, O., Carlone, A., Mazzanti, A., Locatelli, M., Sambri, L., Bartoli, G., Melchiorre, P. CEJ 14, 4788 (2008). 6 Cabrera, S., Aleman, J., Bolze, P., Bertelsen, S., Jorgensen, K.A. ACIE 47, 121 (2008). 7 Ibrahem, I., Rios, R., Vesely, J., Zhao, G.-L., Cordova, A. CC 849 (2007). 8 Ma, A., Zhu, S., Ma, D. TL 49, 3075 (2008). 9 Alonso, D.A., Kitagaki, S., Utsumi, N., Barbas III, C.F. ACIE 47, 4588 (2008). 10 Bertelsen, S., Diner, P., Johansen, R.L., Jørgensen, K.A. JACS 129, 1536 (2007). 11 Ishino, T., Oriyama, T. CL 36, 550 (2007). 12 Aleman, J., Cabrera, S., Maerten, E., Overgaard, J., Jørgensen, K.A. ACIE 46, 5520 (2007). 13 Palomo, C., Landa, A., Mielgo, A., Oiarbide, M., Puente, A., Vera, S. ACIE 46, 8431 (2007). 14 Vo, N.T., Pace, R.D.M., O’Hara, F., Gaunt, M.J. JACS 130, 404 (2008). 15 Zu, L., Li, H., Xie, H., Wang, J., Jiang, W., Tang, Y., Wang, W. ACIE 46, 3732 (2007). 16 Gotoh, H., Ishikawa, H., Hayashi, Y. OL 9, 5307 (2007). 17 Wang, Y., Li, P., Liang, X., Zhang, T.Y., Ye, J. CC 1232 (2008). 18 Reyes, E., Jiang, H., Milelli, A., Elsner, P., Hazell, R.G., Jorgensen, K.A. ACIE 46, 9202 (2007). 19 Garcia-Garcia, P., Ladepeche, A., Halder, R., List, B. ACIE 47, 4719 (2008). 20 Hayashi, Y., Itoh, T., Ohkubo, M., Ishikawa, H. ACIE 47, 4722 (2008). 21 Chi, Y., Guo, L., Kopf, N.A., Gellman, S.H. JACS 130, 5608 (2008). 22 Zhu, S., Yu, S., Ma, D. ACIE 47, 545 (2008). 2

380

3-Pyridinecarboxylic anhydride

23

Liu, F., Wang, S., Wang, N., Peng, Y. SL 2415 (2007). Ibrahem, I., Zhao, G.-L., Cordova, A. CEJ 14, 683 (2008). 25 Palomo, C., Vera, S., Velilla, I., Mielgo, A., Gomez-Bengoa, E. ACIE 46, 8054 (2007). 26 Hayashi, Y., Gotoh, H., Masui, R., Ishikawa, H. ACIE 47, 4012 (2008). 27 Gotoh, H., Hayashi, Y. OL 9, 2859 (2007). 28 Vesely, J., Ibrahem, I., Zhao, G.-L., Cordova, A. ACIE 46, 778 (2007). 29 Sato, I., Toyota, Y., Asakura, N. EJOC 2608 (2007). 30 Goushi, S., Funabiki, K., Ohta, M., Hatano, K., Matsui, M. T 63, 4061 (2007). 31 Chu, Q., Yu, M.S., Curran, D.P. OL 10, 749 (2008). 32 Li, Y., Liu, X., Yang, Y., Zhao, G. JOC 72, 288 (2007). 33 Bondarev, O., Goddard, R. TL 47, 9013 (2006). 24

3-Pyridinecarboxylic anhydride. Ester and amide synthesis. Nicotinic anhydride activates carboxylic acids (by forming mixed anhydrides) to be transformed into esters1 and amides,2 with alcohols and amines, respectively (catalytic DMAP). 1

Mukaiyama, T., Funasaka, S. CL 36, 326 (2007). Funasaka, S., Mukaiyama, T. CL 36, 658 (2007).

2

3-Pyridinesulfonyl chloride. Amide synthesis.1 The title reagent is newly developed for facilitating amide formation from carboxylic acid and amines. In the condensation DMAP serves as catalyst. 1

Funasaka, S., Kato, K., Mukaiyama, T. CL 37, 506 (2008).

4-Pyrrolidinopyridine. Transesteriﬁcation.1 Zwitterionic adduct of 4-pyrrolidinopyridine and an electrondeﬁcient aryl isothiocyanate (e.g., p-nitrophenyl and 3,5-bis(triﬂuoromethyl)phenyl isothiocyanates) catalyzes transesteriﬁcation of methyl esters, requiring only stoichiometric quantity of the alcohol. The reaction is best performed by azeotropic reﬂuxing, with assistance of 5A-molecular sieves to absorb the liberated MeOH. b-Lactones.2 A synthesis of salinosporamide-A highlights the creation of the b-lactone unit from a keto acid. COOH RN O

OR'

N

N

O

O TfO

R"

N Br

i-Pr2NEt / CH2Cl2 1

Ishihara, K., Niwa, M., Kosugi, Y. OL 10, 2187 (2008). Ma, G., Nguyen, H., Romo, D. OL 9, 2143 (2007).

2

R N

R"

OR' O O

(S)-(2-Pyrrolidinyl)methylamines

381

(S)-(2-Pyrrolidinyl)methylamines. Aldol reaction. Triﬂyl and nonaﬂyl derivatives of (S)-(2-pyrrolidinyl)methylamine mediate asymmetric aldol reactions in aqueous media.1,2 The latter is a typically recyclable ﬂuorous catalyst.2 Also reusable is the salts of N-(2-pyrrolidinylmethyl) derivatives 1 of cyclic amines.3

N H H N

3

[PW12O40]3–

(1)

Michael reaction. The greatest number of research reports pertaining to methodology development for the asymmetric Michael reaction are based on the addition of ketones to b-nitrostyrene. Among catalysts 2,4 3,5 and 4,6 the ﬁrst one is the simplest.

O N S O

N H

N H

N N

H

N H

CF3

N

F3C

(2)

(3)

(4)

By means of the “click reaction” compounds containing a 1,2,3-triazole unit (5,7 6 8) have been prepared.

N H

N N N

R

(5) R = N-methylimidazolium (6) R = polymer benzyloxy

382

(S)-(2-Pyrrolidinyl)methylamines

N-Heterocycles quaternized by the (S )-(2-pyrrolidinyl)methyl group constitute another series of useful catalysts. These include 7,9 8,10 and 9.11 Reactions involving 8 and 9 are carried out in ionic liquids.

X N H

N

Br

N H

N

N H

N

Br

N Bu

(7)

(8)

(9)

The thiourea derivative 10 is active in promoting conjugate addition of ketones to b-nitrostyrenes.12

N R

HN

NH S

(10)

N-Arylation. (S)-2-(Imidazolylmethyl)pyrrolidine 11 is yet another derivative of the series, and it functions as a catalyst for N-arylation of heterocyclic amines.13

N R

N N

(11) 1

Mei, K., Zhang, S., He, S., Li, P., Jin, M., Xue, F., Luo, G., Zhang, H., Song, L., Duan, W., Wang, W. TL 49, 2681 (2008). 2 Zu, L., Xie, H., Li, H., Wang, W. OL 10, 1211 (2008). 3 Luo, S., Li, J., Xu, H., Zhang, L., Cheng, J.-P. OL 9, 3675 (2007). 4 Ni, B., Zhang, Q., Headley, A.D. TA 18, 1443 (2007). 5 Vishnumaya, Singh, V.K. OL 9, 1117 (2007).

(S)-(2-Pyrrolidinyl)azoles

383

6

Chen, H., Wang, Y., Wei, S., Sun, J. TA 18, 1308 (2007). Wu, L.-Y., Yan, Z.-Y., Xie, Y.-X., Niu, Y.-N., Liang, Y.-M. TA 18, 2086 (2007). 8 Alza, E., Cambeiro, X.C., Jimeno, C., Pericas, M.A. OL 9, 3717 (2007). 9 Ni, B., Zhang, Q., Headley, A.D. TL 49, 1249 (2008). 10 Xu, D.Q., Wang, B.-T., Luo, S.-P., Yue, H.-D., Wang, L.-P., Xu, Z.-Y. TA 18, 1788 (2007). 11 Luo, S., Zhang, L., Mi, X., Qiao, Y., Cheng, J.-P. JOC 72, 9350 (2007). 12 Cao, Y.-J., Lai, Y.-Y., Wang, X., Li, Y.-J., Xiao, W.-J. TL 48, 21 (2007). 13 Zhu, L., Cheng, L., Zhang, Y., Xie, R., You, J. JOC 72, 2737 (2007). 7

(S)-(2-Pyrrolidinyl)azoles. Michael reaction.1 Enantioselective addition of ketones to b-nitrostyrene is performed with the disubstituted triazole 1. Surprisingly, 1 is not a good catalyst for the aldol reaction.

N R

N N

N Ph

(1)

Mannich reaction. With the 2-(5-tetrazolyl)-4-siloxypyrrolidine 2, enantioselective and diastereoselective Mannich reaction proceeds in water.2

TBSO

N R

HN N

N

(2) 1

Chandrasekhar, S., Tiwari, B., Parida, B.B., Reddy, C.R. TA 19, 495 (2008). Hayashi, Y., Urushima, T., Aratake, S., Okano, T., Obi, K. OL 10, 21 (2008).

2

R Rhenium carbonyl clusters. N-Alkenylattion.1 Heating a lactam and a 1-alkyne with Re2(CO)10 in toluene gives the N-alkenyl derivative. NH

+

Re2(CO)10

R

N

PhMe

R O

O 1

Yudha S, S., Kuninobu, Y., Takai, K. OL 9, 5609 (2007).

Rhodium/alumina. Hydrogenation. The Rh/Al2O3 catalyst is well suited for hydrogenation of pyrrole derivatives to furnish pyrrolidines. 1

Jiang, C., Frontier, A.J. OL 9, 4939 (2007).

Rhodium(II) carboxamidates. Cycloadditions. The carboxamidate 1 has been used to catalyze the 1,3-dipolar cycloaddition of nitrones with enals.1

O

O

N O

Rh Rh SbF6

(1) Oxidation. Caprolactamate of Rh catalyzes oxidation of alkynes to furnish conjugated alkynones with t-BuOOH in water.2 1

Wang, Y., Wolf, J., Zavalij, P., Doyle, M.P. ACIE 47, 1439 (2008). McLaughlin, E.C., Doyle, M.P. JOC 73, 4317 (2008).

2

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 385

386

Rhodium(II) carboxylates

Rhodium(II) carboxylates. Transylidation. Aryliodonium ylides of the ArIvCHTf2 type can be prepared from heating ArI (in large excess) with PhIvCHTf2 and Rh2(OAc)4 at 908.1 Transylidation is involved in the O-benzylation of 2-aryliodonio-1,3-cycloalkanedionates with retention of conﬁguration.2

O

O I

Ph

O

I

Rh2(OAc)4

+ Ar

X

O

Ar

Bond insertion. A gainful application of the intramolecular Rh-carbenoid insertion into a CZH bond is described in a synthesis of clasto-lactacystin b-lactone.3

O O S Ph N2

O

O

O N

Rh2(OAc)4

O S Ph

O

CH2Cl2

OH

O

H

O

O

NH

N

O clasto-lactacystin -lactone

85%

Divergent pathways are pursued by Rh-carbenoids generated from a-diazoarylacetic esters in the reaction with 1-arylpropenes. Steric crowding favors CZH bond insertion.4

Rh2(OCOCPh3)4

Ar'

Ar

Ar

COOMe

+ Ar'

Ar

N2 COOMe COO

Rh

COO

Rh 2

Ar' COOMe

= Rh2(esp)2

Diastereoselective formation of 2-alkoxy-3-aminoalkanoic esters is observed from a reaction of a-diazo esters, alcohols, and imines. Oxonium ylides are formed and trapped.5

Rhodium(II) carboxylates

Ph

COOMe N2

Ph

Rh2(OAc)4

Ar

+ ROH

COOMe

RO Ar'

+ NR'

387

NHR'

Formation of dioxolanes as the major products from a-diazoalkanoic esters and ArCHO is the result of a 1,3-dipolar cycloaddition.6 R R Rh2(OCOCMe3)4

ArCHO

+

N2 COOR'

CH2Cl2

O

Ar

COOR'

O

78o

Ar

A useful Rh-nitrenoid is generated from TsONHCOOCH2CCl3 and it can be used to functionalize tetrahydrofuran.7 O + O

Rh

O N

TsNH

O

O Rh 4 O

O

CCl3

(1) CH2Cl2 25o

O

(1)

HN COOCH CCl 2 3 84%

Bicyclization via nitrenoid-to-carbenoid transition followed by OZC bond insertion8 serves to demonstrate the power of the reactions catalyzed by Rh carboxylates and the beneﬁt of substrate design to accommodate functional participations.

O O S O

OSO2NH2 Rh2(esp)2

O

PhI(OAc)2 CH2Cl2 25o

O

(Z )-a-Azidocinnamic esters cyclize to afford 2-indolecarboxylic esters on thermolysis (1458). The reaction temperature is lowered to 308 –608 by catalysis of Rh2(OCOC3F7)4 [but not by Rh2(OAc)4].9 Similarly, 2-arylindoles are synthesized from o-azidostilbenes by warming with Rh2(OCOC3F7)4 and 4A-molecular sieves in toluene at 608.10

388

Rhodium(II) carboxylates

Under oxidative conditions sultones are formed from alkoxysulfonylacetic esters.11 The active methylene group is transformed into a Rh-carbenoid to accomplish the bond insertion. O O

O

O

COOEt

S

O S

O

Rh2(OAc)4

COOEt

PhIO, Cs 2CO3

Ph

Ph 80%

Ligand control of the reaction pathway is manifested in the formation of either a cyclopropene or a dihydroazulene.12

COOEt

Ph N2

+

+

O

Ph

Rh

R

75%

Rh

O Ph

COOEt

Ph

R = t-Bu

4 R = CPh3

COOEt Ph 49%

Bicyclization. Carbonyl ylides generated via decomposition of diazoketones and internal trapping can be put to good use. Accessibility of oxabridged tricyclic by an intramolecular [3þ2]cycloaddition has profound signiﬁcance to the elaboration of the core structure of platensimycin, and the possibility has been studied. Initial experimentation showed the preponderant formation of an isomeric skeleton but by halogen substitution (change of HOMO coefﬁcient) on the dipolarophilic alkene the desired intermediate can be prepared as the major product.13 X X

O N2 CN

O

X

Rh2(OAc)4 CH2Cl2

O

+ CN O

X=H

65%

X = Br, I

8–9% platensimycin

O CN O trace 82–83%

Rhodium(II) carboxylates

389

Benzyl alcohols. After transmetallation arylboronic acids are converted into arylrhodium species that are nucleophilic toward various aldehydes. A very active catalyst (1) is that derived from Rh2(OAc)4, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride and t-BuOK.14

N

O

O

Rh

Rh

N

ArB(OH)2

+

RCHO

N (1)

N

t-BuOK

R

Ar OH

(1)

N-Sulfonylcarboxamides. A mixture of Rh2(esp)2 and PhI(piv)2 can be used to bring about oxidative sulfamidation of aldehydes.15

Rh2(esp)2

RCHO + R'SO2NH2

PhI(OCOCMe3)2

RCONHSO2R'

Isomerization. 3-Aryl-3H-azirines undergo isomerization to furnish indoles by heating with Rh2(OCOCF3)4 in 1,2-dichloroethane.16

R

R' N

1

R Rh2(OCOCF3)4

R'

ClCH2CH2Cl

N H

Ochiai, M., Okada, T., Tada, N., Yoshimura, A. OL 10, 1425 (2008). Moriarty, R.M., Tyagi, S., Ivanov, D., Constantinescu, M. JACS 130, 7564 (2008). 3 Yoon, C.H., Flanigan, D.L., Yoo, K.S., Jung, K.W. EJOC 37 (2007). 4 Davies, H.M.L., Coleman, M.G., Ventura, D.L. OL 9, 4971 (2007). 5 Huang, H., Guo, X., Hu, W. ACIE 46, 1337 (2007). 6 DeAngelis, A., Panne, P., Yap, G.P.A., Fox, J.M. JOC 73, 1435 (2008). 7 Lebel, H., Huard, K. OL 9, 639 (2007). 8 Thornton, A.R., Blakey, S.B. JACS 130, 5020 (2008). 9 Stokes, B.J., Dong, H., Leslie, B.E., Pumphrey, A.L. JACS 129, 7500 (2007). 10 Shen, M., Leslie, B.E., Driver, T.G. ACIE 47, 5056 (2008). 11 Wolckenhauer, S.A., Devlin, A.S., Du Bois, J. OL 9, 4363 (2007). 12 Panne, P., Fox, J.M. JACS 129, 7500 (2007). 13 Kim, C.H., Jang, K.P., Choi, S.Y., Chung, Y.K., Lee, E. ACIE 47, 4073 (2008). 2

390

Rhodium(III) chloride

14

Trindale, A.F., Gois, P.M.P., Veiros, L.F., Andre, V., Duarte, M.T., Afonso, C.A.M., Caddick, S., Cloke, F.G.N. JOC 73, 4076 (2008). 15 Chan, J., Baucom, K.D., Murry, J.A. JACS 129, 14106 (2007). 16 Chiba, S., Hattori, G., Narasaka, K. CL 36, 52 (2007).

Rhodium(III) chloride. De-N-allylation.1 The N-allyl group of an amide is selectively removed by heating with RhCl3 in isopropanol. [21212]Cycloaddition. In the presence of RhCl3 . 3H2O and i-Pr2NEt alkynes are trimerized to provide substituted benzenes,2 a mixture of a diyne and an alkyne forms a 1 : 1-adduct.3 R

R' MeOOC

R

MeOOC

R

+ R'

RhCl3 · 3H2O

MeOOC

i-Pr2NEt

MeOOC

R' R'

PhMe

R

Oxidative coupling.4 2,3-Bis(b-indolyl)maleimides are converted into hexacyclic products on heating with RhCl3 . 3H2O and Cu(OAc)2 in DMF.

Bn N

O

O R

R N H

N H

Bn N

O RhCl3 · 3H2O

O R

R

Cu(OAc)2 · H2O DMF

N H R =, H, OMe, F

N H 73–78%

1

Zacuto, M.J., Xu, F. JOC 72, 6298 (2007). Yoshida, K., Morimoto, I., Mitsudo, K., Tanaka, H. CL 36, 998 (2007). 3 Yoshita, K., Morimoto, I., Mitsudo, K., Tanaka, H. T 64, 5800 (2008). 4 Witulski, B., Schweikert, T. S 1959 (2005). 2

Rhodium hydroxide/alumina. Amide formation.1 Redox reaction between aldehydes and hydroxylamine leads to carboxamides. The reaction, catalyzed by Rh(OH)n in water at 1608, perhaps proceeds via oxime formation, dehydration and rehydration. 1

Fujiwara, H., Ogasawara, Y., Yamaguchi, K., Mizuno, N. ACIE 46, 5202 (2007).

Ruthenium – carbene complexes

391

Rhodium(III) iodide. Strecker reaction.1 Aldehydes and amines are condensed with Me3SiCl under the inﬂuence of RhI3 . H2O in MeCN at room temperature. 1

Majhi, A., Kim, S.S., Kadam, S.T. T 64, 5509 (2008).

Rhodium(I) tetraﬂuoroborate. Isomerizations. The Rh(I) salt causes intramolecular redox transformation of propargylic alcohols to provide conjugated carbonyl compounds. Depending on the nature of the carbon unit attached to the far end of the triple bond different ligands are required for optimal reaction.1

OH R

O

RhBF4

R

R'

R'

R = Ar, ligand: BINAP, solvent: ClCH2CH2Cl R = Alkenyl, ligand: Ph 2PCH2CH2PPh2, solvent: ClCH 2CH2Cl R = Alkyl, ligand: Cy 2PCH2CH2PCy2, solvent: CH 2Cl2 1

Tanaka, K., Shoji, T., Hirano, M. EJOC 2687 (2007).

Ruthenium–carbene complexes. General aspects and new metathesis catalysts. For alkene metathesis Grubbs I (1) and Grubbs II (2, 3) complexes, and the Grubbs–Hoveyda catalyst (4A) and Grela catalyst (4B) remain the workhorses.

Cy3P Cl Ru Ph Cl PCy3

Ru Cl

N Cl

N

N Cl

N

Ru Ph

PCy3

Cl O

X

(1) (2) imidazolene (3) imidazolidene

(4A) R = H (4B) R = NO2

Insights for asymmetric metathesis of alkenes1 should guide future developments. Chiral catalysts 52 and 63 have been synthesized.

392

Ruthenium –carbene complexes

Ph

Ph

N I

N

O N Cl Ph

H

Ru

O

Ru

PCy3

O

O

(5 )

Ph

(6 ) A review has summarized the positive effects of microwaves.4 Acetic acid is found to be a good solvent for RCM using Grubbs II catalyst.5 The annoying problem of double bond migration in substrates that contain hydrogen-bonding groups is solved by adding phenylphosphoric acid.6 Cross metathesis in water at room temperature based on Grubbs II catalyst is facilitated by a nonionic amphiphile, which is a PEG linked to vitamin-E through sebacoyl chloride.7 At the end of a metathesis reaction treatment with NCCH2COOK in MeOH renders the Grubbs II catalyst inactive by transforming it into 7.8

N

N

Cl Ph KOOCH 2CNC Ru CN–CH2COOK Cl PCy3

(7 ) Several modiﬁcations of the commonly used catalysts have been reported during the 2007–2008 period. For example, one with a PEG chain bonded to the imidazolidine ring of the conventional Grubbs II catalyst has the advantage of easy removal by aqueous extraction.9 The presence of an amide residue in the Grubbs–Hoveyda catalyst (as in 8) also makes its separation from products easier.10 As for the development of catalysts for use in aqueous environment, the strategy of attaching a chain containing ammonium group(s) has borne mixed results. Complexes like 9 can be employed in ROMP (ring opening metathetic polymerization) and RCM, but they are not stable enough to effect crossmetathesis.11

Ruthenium – carbene complexes

N Cl

N

N Cl

N

N

Ru

Ru

N

Cl

Cl O

O

NHCOR

(8 )

393

2Cl

(9 )

Ruthenium complex 10 is a dormant RCM catalyst, activatable by various acids.12 After the metathesis reaction, it is re-formed by treatment with SiO2. Catalysts with lessening steric congestion adjacent to the carbene center (e.g., 1113 and 1214) are favorable to RCM reactions in order to form tetrasubstituted alkenes.

O O

Ru

Ru

Ru

N Cl

N

N Cl

N

N Cl

N

Cl

Cl

O

O

O

(10)

(11)

Ph

(12)

For cross metathesis of alkenes, it is found that in the preparation of disubstituted alkenes with one or more allylic substituents Grubbs–Hoveyda catalysts possessing N-(o-tolyl) groups in the azolecarbene unit are more efﬁcient than those with the N-mesityl groups. But for the formation of trisubstituted alkenes the N-mesityl catalysts are superior due to discrimination between productive and nonproductive reaction pathways.15 R' [Ru]

R' [Ru]

R productive intermediate

R unproductive intermediate

There is a catalyst (13) in which the phosphine ligand is ionophilic.16 The Hoveyda-type complexes 14 possessing a hindered pyrrolidine carbene ligand show comparable activities to the standard catalysts.17

394

Ruthenium –carbene complexes

N Cl

N Ru Cl

N Cl

Ph

Ru

PCy2

N

Cl O

N Tf2N

(14) (13)

3-Arylthiazol-2-ylidene ligands have also been investigated as replacements for the imidazole/imidazolidene portion of the established catalysts for alkene metathesis. Promising results have been obtained from 15.18 Another novel catalyst is exempliﬁed by 16.19 R N Cl

S Ru

R O2N R O Cl

Cl O

(15)

N Ru Ph PCy3

(16)

Metathesis catalysts with one chiral N-substituent (e.g., 17) are useful for ROMP.20 In alternating copolymerization of norbornene with other cycloalkenes the steric interactions of the growing polymer chain dictate selectivity.

N Cl

N Ru Cl

Ph

X

(17) Novel and highly active RCM catalysts that contain anionic or neutral carborane tags have been developed. Their uses in promoting standard RCM in CH2Cl2 at 308 have been demonstrated.21 The modiﬁed Grubbs I catalyst 18 is effective for RCM of functionalized dienes and enynes.22

Ruthenium – carbene complexes

Cy

395

P

Cl Cl

Ru Ph P

Cy

(18) Cross-metathesis reactions. The valuable cinnamylation reagent and other homologous allylation reagents are readily accessible from cross-metathesis using the Grubbs II catalyst.23 Ph

O

Ph

(3)

Si N Me

O

+

Cl

Si Cl N Me

Ar

Ar

Cross-metathesis of alkenes with 1,2-dichloroethene under the inﬂuence of 4B provides 1-chloroalkenes.24 The cross-metathesis approach to a-alkylidene g-butyrolactones is fraught with danger of double bond migration, and it is circumvented by addition of catecholchloroborane25 or 2,6-dichloro-1,4-benzoquinone.26 However, the method cannot be used to synthesize a-alkylidene d-valerolactones.26 O

O (3)

+

O

R

O

CH2Cl2

R

Cl

additive:

O O BCl

or

O

O Cl

Grubbs II catalyst does not lose activity during cross-metathesis of v-alkenols with 1-alkynes.27 Bridged ring systems with a strained double bond are highly susceptible to cross metathesis accompanied by ring opening. A synthesis of unsymmetrical cis-2,6-dialkenylpiperidines is an application based on this nature.28 OTBS

OTBS R N

+ Ph

N R

Ph

396

Ruthenium –carbene complexes

An ester group located at a bridgehead (C-1) of 7-azanorbornenes has strong directing effect on the ring-opening cross-metathesis.29 R N

Boc

O

H +

(4A)

NBoc

COR COOMe

MeOOC

When the Diels–Alder adduct of cyclopentadiene and allyl nitrosyl ketone undergoes ring-opening cross-metathesis it is converted into a fused ring system.30 O

O O

O N

+

N

Me3Si

H

Me3Si

H

3,3-Disubstituted cyclopropenes undergo ring-opening cross-metathesis with certain alkenes under the inﬂuence of 6 to produce (3S)-1,4-alkadienes.3 O +

O (6)

O

O RL

RL

1,3-Transposition of Ru-carbenoid prior to cross-metathesis is an important feature for the attachment of an allylic ester unit to the terminus of a diyne.31 R

R

O

R

[Ru]

O O

(3) CH2Cl2

O O

O O

40o

[Ru]

OAc OAc R OAc

O O

Ruthenium – carbene complexes

397

In case one of the cross-metathesis partners is attached to a polymer, it is better to place a longer linker in between in order to maximize the reaction efﬁciency.32 Using the Grubbs catalysts to mediate cross-metathesis of more intransigent substrates, the application of microwaves often shows improvements.33 The cause of the failure of the Grubbs II catalyst to achieve cross-metathesis of vinyl chloride is ascribed to the rapid elimination of HCl from the chlorovinyldene carbenoid or the exchange of the chlorine atom into a Cy3P group.34 Stepwise cross-metathesis of divinyl sulfones readily provides unsymmetrical dialkenyl sulfones.35 Metathetic ring closure. Based on Grubbs I catalyst RCM involving a terminal alkyne unit and an allylic alcohol is actually accelerated by the presence of the OH group.36 Closure of macrocycles under kinetic control and thermodynamic control might lead to different ratios of (E/Z)-isomers. It is interesting that reactions under the inﬂuence of Grubbs I catalyst and Grubbs II catalyst can be so differentiated.37 OPMB

OH O

OH O O

OPMB O

(1) CH2Cl2

O

O

O O

Stereoselective access to 1,6-diol derivatives from siloxanes bearing two unsaturated carbon chains is shown to be amenable to asymmetric induction.38 This achievement has profound implications to the synthesis of certain insect pheromones.

O TfO

Si

Si

OTf

O

Si

O

(1)

O

OTf

O O an insect pheromone

O O

Si

O

398

Ruthenium –carbene complexes

The nature of the N-substituent is of critical importance for macrocyclic RCM of a trans2-vinyl-1-amidocyclopropane because it affects the choice of the initial site of Ru-carbenoid formation. An acyl group favors RCM even at high substrate concentration.39

RO

R'OOC

X N

[Ru] carbene formation site dependent on X

COOMe

N

H N

O

X = Ac, Boc (leading to macrocycle)

O

X = H, Bn

RCM is shown to be applicable to synthesis of benzannulated quinolizines.40

(4A)

N

N TfO

TfO

Rapid access to salient heteroannular dienes by RCM of dienynes is represented by synthetic approaches to colchicine41 and the bicyclo[5.3.1]undeca-1,9-diene system.42 MeO (3)

MeO MeO

OSiMe3

CH2Cl2

MeO RO MeO MeO 74%

R R

H H

OH

H H

(1)

H

OH H

Ruthenium – carbene complexes

399

The RCM of polypeptides containing terminal alkene units performed under microwaves gives better yields of the desired products.43 It is also signiﬁcant that 1-alkenylcyclobutenes are formed by the RCM method.44

(4A)

R

R"

R

CH2Cl2

R'

R" R'

w

Tandem reactions. The multiple activities of the Ru catalysts enable development of valuable tandem reactions. Further extension of the carbon chain of a conjugated enal obtained from a cross-metathesis reaction is readily achieved on treatment with diazoacetic esters to give alkadienoic esters.45

R

(3)

CHO

+

Ph3P

CHO

R

N2

R'

COOEt

R'

COOEt R R'

A use of 4A is in the synthesis of 4-substituted tetrahydrocarbazoles and tetrahydro-bcarbolines,46 involving cross-metathesis and intramolecular hydroarylation.

O X O

Z +

(4A)

X

N R X = Me, OEt

Z

ClCH2CH2Cl

N R

The stability of 4A in the presence of BF3 . OEt2 is apparently critical to the synthesis of azacycles containing a 2-oxoalkyl chain at C-2 by cross-metathesis of 1-alken-3ones with v-alkenamines. The Lewis acid is responsible for the intramolecular Michael reaction.47 Sequential Heck reaction and hydrosilylation of carbonyl have been carried out with the Grubbs I catalyst.48 Allylic alcohols can be synthesized via conjugated carbonyl compounds prepared from cross-metathesis in situ by reduction with i-Bu2AlH.49 An access to enantiomeric 2,3-dihydroxyalkanoic esters is based on cross-metathesis, dihydroxylation and methanolysis.50

400

Ruthenium –carbene complexes

O O N R

+

S

O O

H

OH

(4A), EtOAc;

H

MIO4

COOMe

R

OH

O O N R

+

H

S

O OH

(4A), EtOAc; MIO4

R

COOMe OH

Isomerization. A terminal double bond migrates by one carbon inward along the carbon chain (but no further) on heating with Grubbs II catalyst in MeOH.51 Thus, 2-allylcyclohexanone is converted to 2-propenylcyclohexanone. Maleic esters. Diazoacetic esters furnish maleic esters on treatment with Grubbs II catalyst. Such reaction is applicable to the synthesis macrodilactides.52 1

Berlin, J.M., Goldberg, S.D., Grubbs, R.H. ACIE 45, 7591 (2006). Samec, J.S.M., Grubbs, R.H. CC 2826 (2007). 3 Giudici, R.E., Hoveyda, A.H. JACS 129, 3824 (2007). 4 Coquerel, Y., Rodriguez, J. EJOC 1125 (2008). 5 Adjiman, C.S., Clarke, A.J., Cooper, G., Taylor, P.C. CC 2806 (2008). 6 Gimeno, N., Formentin, P., Steinke, J.H.G., Vilar, R. EJOC 918 (2007). 7 Lipshutz, B.H., Aguinaldo, G.T., Ghorai, S., Voigtritter, K. OL 10, 1325 (2008). 8 Galan, B.R., Kalbarczyk, K.P., Szczepankiewicz, S., Keister, J.B., Diver, S.T. OL 9, 1203 (2007). 9 Hong, S.H., Grubbs, R.H. OL 9, 1955 (2007). 10 Rix, D., Caijo, F., Laurent, I., Boeda, F., Clavier, H., Nolan, S.P., Mauduit, M. JOC 73, 4225 (2008). 11 Jordan, J.P., Grubbs, R.H. ACIE 48, 5152 (2007). 12 Gawin, R., Makal, A., Wozniak, K., Mauduit, M., Grela, K. ACIE 46, 7206 (2007). 13 Berlin, J.M., Campbell, K., Ritter, T., Funk, T.W., Chlenov, A., Grubbs, R.H. OL 9, 1339 (2007). 14 Stewart, I.C., Ung, T., Pletnev, A.A., Berlin, J.M., Grubbs, R.H., Schrodi, Y. OL 9, 1589 (2007). 15 Stewart, I.C., Douglas, C.J., Grubbs, R.H. OL 10, 441 (2008). 16 Consorti, C.S., Aydos, G.L., Ebeling, G., Dupont, J. OL 10, 237 (2008). 17 Anderson, D.R., Lavallo, V., O’Leary, D.J., Bertrand, G., Grubbs, R.H. ACIE 46, 7262 (2007). 18 Vougioukalakis, G.C., Grubbs, R.H. JACS 130, 2234 (2008). 19 Occhipinti, G., Jensen, V.R., Bjorsvik, H.-R. JOC 72, 3561 (2007). 20 Vehlow, K., Wang, D., Buchmeiser, M.R., Blechert, S. ACIE 47, 2615 (2008). 21 Liu, G., Zhang, J., Wu, B., Wang, J. OL 9, 4263 (2007). 22 Boeda, F., Clavier, H., Jordaan, M., Meyer, W.H., Nolan, S.P. JOC 73, 259 (2008). 23 Huber, J.D., Perl, N.R., Leighton, J.L. ACIE 47, 3037 (2008). 24 Sashuk, V., Samojlowicz, C., Szadkowska, A., Grela, K. CC 2468 (2008). 25 Moise, J., Arseniyadis, S., Cossy, J. OL 9, 1695 (2007). 26 Raju, R., Allen, L.J., Le, T., Taylor, C.D., Howell, A.R. OL 9, 1699 (2007). 27 Clark, D.A., Clark, J.R., Diver, S.T. OL 10, 2055 (2008). 28 Cortez, G.A., Baxter, C.A., Schrock, R.R., Hoveyda, A.H. OL 9, 2871 (2007). 2

Ruthenium(III) chloride

401

29

Carreras, J., Avenoza, A., Busto, J.H., Peregrina, J.M. OL 9, 1235 (2007). Calvert, G., Blanchard, N., Kouklovsky, C. OL 9, 1485 (2007). 31 Cho, E.J., Lee, D. OL 10, 257 (2008). 32 Garner, L., Koide, K. OL 9, 5235 (2007). 33 Michaut, A., Boddaert, T., Coquerel, Y., Rodriguez, J. S 2867 (2007). 34 Macnaughton, M.L., Johnson, M.J.A., Kampf, J.W. JACS 129, 7708 (2007). 35 Bieniek, M., Koloda, D., Grela, K. OL 8, 5689 (2006). 36 Imahori, T., Ojima, H., Tateyama, H., Mihara, Y., Takahara, H. TL 49, 265 (2008). 37 Matsuya, Y., Takayanagi, S., Nemoto, H. CEJ 14, 5275 (2008). 38 Hooper, A.M., Dufour, S., Willaert, S., Pouvreau, S., Pickett, J.A. TL 48, 5991 (2007). 39 Shu, C., Zeng, X., Hao, M.-H., Wei, X., Yee, N.K., Busacca, C.A., Han, Z., Farina, V., Senanayake, C.H. OL 10, 1303 (2008). 40 Nunez, A., Cuadro, A.M., Alvarez-Builla, J., Vaquero, J.J. OL 9, 2977 (2007). 41 Boyer, F.-D., Hanna, I. OL 9, 2293 (2007). 42 Aldegunde, M.J., Garcia-Fandino, R., Castedo, L., Granja, J.R. CEJ 13, 5135 (2007). 43 Chapman, R.N., Arora, P.S. OL 8, 5825 (2006). 44 Debleds, O., Campagne, J.-M. JACS 130, 1562 (2008). 45 Murelli, R.P., Snapper, M.L. OL 9, 1749 (2007). 46 Chen, J.-R., Li, C.-F., An, X.-L., Zhang, J.-J., Zhu, X.-Y., Xiao, W.-J. ACIE 47, 2489 (2008). 47 Fustero, S., Jimenez, D., Sanchez-Rosello, M., del Pozo, C. JACS 129, 6700 (2007). 48 Ackermann, L., Born, R., Alvarez-Bercedo, P. ACIE 46, 6364 (2007). 49 Paul, T., Sirasani, G., Andrade, R.B. TL 49, 3363 (2008). 50 Neisius, N.M., Plietker, B. JOC 73, 3218 (2008). 51 Hanessian, S., Giroux, S., Larsson, A. OL 8, 5481 (2006). 52 Hodgson, D.M., Angrish, D. CEJ 13, 3470 (2007). 30

Ruthenium(III) chloride. Alkylation. Indoles are alkylated by epoxides at C-3 under solvent-free conditions in the presence of RuCl3 . xH2O.1 Hydrogenation. b-Hydroxy ketones are hydrogenated in MeOH to give anti-1,3-diols using RuCl3 – Ph3P as catalyst.2 Hydrogenation of monosubstituted and 1,2-disubstituted alkenes is achieved by NaBH4 when RuCl3 . xH2O is also added.3 Coupling reactions. N-Atom directed o-arylation of the aromatic nucleus of a 2-aryl4,5-dihydrooxazole proceeds readily on heating with ArBr, RuCl3 . xH2O, and K2CO3 in NMP.4 2-Phenylpyridine and congeners also undergo analogous arylation. Arylation at both unsubstituted o-positions is observed when (PhCOO)2 is present.5 OMe

O

N coupling site

N coupling site

N coupling site

402

Ruthenium carbonyl clusters

1

Tabatabaeian, K., Mamaghani, M., Mahmoodi, N.O., Khorshidi, A. TL 49, 1450 (2008). Labeeuw, O., Roche, C., Phansavath, P., Genet, J.-P. OL 9, 105 (2007). 3 Sharma, P.K., Kumar, S., Kumar, P., Nielsen, P. TL 48, 8704 (2007). 4 Ackermann, L., Althammer, A., Born, R. T 64, 6115 (2008). 5 Cheng, K., Zhang, Y., Zhao, J., Xie, C. SL 1325 (2008). 2

Ruthenium carbonyl clusters. a-Pyrones.1 A synthesis of a-pyrones is based on assemblage of CO, alkynes and conjugated carbonyl compounds in the presence of Ru3(CO)12.

O

CO

Me3Si

Me3Si

O

+

O

Ru3(CO)2 Et2NMe · HI

R"

R

PhMe 160o

R R"

R" R"

1

Fukuyama, T., Higashibeppu, Y., Yamaura, R., Ryu, I. OL 9, 587 (2007).

Ruthenium oxide –sodium periodate. Oxidation. N-Heterocycles such as isoxazolines are oxidized to give the corresponding lactams.1 N-Boc derivatives of cyclic amines undergo ring opening to afford N-Boc v-amino acids.2

OAc

OAc RuO4 –NaIO4

O

EtOAc, H2O

N R

O O

RuO4 –NaIO4 t-BuOH, H2O

NBoc RuO4 – NaIO4 EtOAc, H2O

1

N R

COOH NHBoc O NBoc

Piperno, A., Chiacchio, U., Iannazzo, D., Giofre, S.V., Romeo, G., Romeo, R. JOC 72, 3958 (2007). Kaname, M., Yoshifugi, S., Sashida, H. TL 49, 2786 (2008).

2

S Samarium. Coupling reaction. a-Bromo-a-halo ketones are converted into a-allyl-a-halo ketones by treatment with Sm and allyl bromide.1 Cyclopropanation. A Sm-carbenoid is formed from Sm and CHI3, which adds to conjugated carboxylic acids stereoselectively. The products also suffer hydrodeiodination.2

R

COOH Sm/CHI3

R'

R

COOH

R'

Reduction. Reduction of RCOCl to RCHO is achieved by samarium and a stoichiometric quantity of Bu3P in MeCN at 2208.3 It does not seem to be a practical method. 1

Di, J., Zhang, S. SL 1491 (2008). Concellon, J.M., Rodriguez-Solla, H., Simal, C. OL 9, 2685 (2007). 3 Jia, X., Liu, X., Li, J., Zhao, P., Zhang, Y. TL 48, 971 (2007). 2

Samarium(III) chloride. C-Acylation.1 1,3-Dicarbonyl compounds undergo C-acylation at room temperature when mediated by SmCl3 –Et3N. 1

Shen, Q., Huang, W., Wang, J., Zhou, X. OL 9, 4491 (2007).

Samarium(II) iodide. Alcoholysis. N-Acyloxazolidinones are cleaved and turned into esters by reaction with ROH in the presence of SmI2.1 Addition to CvO. Organosamarium reagents, formed by treatment of t-butyl a-haloalkyl ketones with SmI2 in THF at 2788, are active toward carbonyl compounds.2 Elimination. 2-Bromo-3-hydroxy-1-nitroalkanes, readily prepared from RCHO and bromonitromethane, are converted into 1-nitroalkenes with SmI2.3 (Z)-Allyltrimethylsilanes are obtained by treatment of 2-acetoxy-3-chloro-1-trimethylsilylalkanes with SmI2.4

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 403

404

Samarium(II) iodide

Elimination of two vicinal p-triﬂuoromethylbenzoyloxy group to place an exocyclic double bond in a polyfunctional cyclononadiyne is a synthetically challenging task. Its accomplishment by using SmI2 is pleasing.5 CF3 F3C

O O

O

O NH OMe O Cl

H O

O O

SmI2

NH OMe O Cl

H

O O

O

THF –50o

OMe

OMe

MeO

MeO

Reduction– addition. On reductive opening of epoxides in the presence of pyridines the radicals are intercepted, therefore 2-(b-hydroxyalkyl)pyridines such as chiral ligands 1 are readily accessible on the basis of this reaction.6

N

SmI2

O

+ N

N

THF 23o

R

N

OH HO R

R

(1) An important service of SmI2 is in the diastereoselective reductive closure to form a spirooxindole.7 S

S

S O

H

S O

SmI2 – LiCl

H H

t-BuOH, THF

N

C

O

–78 o

O N H 71% (dr 7 : 1)

The reduction of alkenyl sulfones accompanied by intramolecular trapping by an aldehyde to form 3-hydroxytetrahydropyrans is synthetically useful because the products are adorned with desirable functional groups.8 R

O

SO2Ph CHO

SmI2

R

O

SO2Ph

MeOH, THF 0o

OH

Samarium(II) iodide

405

Reduction. The selective reduction of d-lactones to diols by SmI2 –H2O in THF has been observed.9 It is attributed to stabilization of the radical anions by interaction with the lone pair electrons on both endocyclic and exocyclic oxygen atoms. g-Lactones survive the reaction conditions.

O

O

H2O, THF 23o

O O

OH

SmI2

O

OH O 80%

2,3-Diaryl-1,3-butadienes are obtained from ArCOMe directly by the reaction with SmI2 and Ac2O in reﬂuxing THF.10 Transannular addition of ketyl species generated from mesocyclic ketones to a double bond is quite efﬁcient.11

OH SmI2

O

t-BuOH, PhSH THF, HMPA

H 62%

O

Ph

OH Ph SmI2 t-BuOH, PhSH THF, HMPA

73%

In the tandem addition involving ketyl radicals and two unsaturated CC bonds, the HMPA additive plays an important role in completing the spiro[4.5]decanes. If Sm instead of HMPA is present the reaction stops at monocyclic products.12

R R

X

O

SmI2

R'

X

R'

t-BuOH THF, HMPA

OH

It is highly signiﬁcant that the naphthalene system is susceptible to an intramolecular attack by a ketyl radical generated from a ketone.13

406

Samarium(II) iodide

H n Z

SmI2

O

n Z

H

t-BuOH, HMPA

H

OH

Z = CH2, NR, C(OCH2)2

The observation that reduction of the cyclopentanone in a precursor of (þ)-brefeldin-A by SmI2 with i-PrOH as proton source to give predominantly the a-alcohol is a desirable result. Many other conditions favor the production of the b-alcohol (e.g., t-BuLi, Dibal-H: 100% b-isomer).14 OH

O

H

H OH

H

OH H OH

H +

OBn OBn

OBn OBn SmI2, i-PrOH, 0o

t-BuLi, Dibal-H, –78o

H OH

OBn OBn

5 : 1 (89%) 0 : 100 (95%)

Both nitroalkanes and conjugated nitroalkenes are reduced to saturated primary amines by SmI2 in THF with i-PrNH2 and H2O as additives.15 Intramolecular reductive cyclization involving a conjugated ester and a d-keto group leads to the formation of cyclopropanolactone.16

O

O COOMe O

H

SmI2

1

Magnier-Bouvier, C., Reboule, I., Gil, R., Collin, J. SL 1211 (2008). Sparling, B.A., Moslin, R.M., Jamison, T.F. OL 10, 1291 (2008). 3 Concellon, J.M., Bernad, P.L., Rodriguez-Solla, H., Concellon, C. JOC 72, 5421 (2007). 4 Concellon, J.M., Rodriguez-Solla, H., Simal, C., Gomez, C. SL 75 (2007). 5 Komano, K., Shimamura, S., Inoue, M., Hirama, M. JACS 129, 14184 (2007). 6 Plummer, J.M., Weitgenant, J.A., Noll, B.C., Lauher, J.W., Wiest, O., Helquist, P. JOC 73, 3911 (2008). 2

Scandium(III) triﬂate

407

7

Reisman, S.E., Ready, J.M., Weiss, M.M., Hasuoka, A., Hirata, M., Tamaki, K., Ovaska, T.V., Smith, C.J., Wood, J.L. JACS 130, 2087 (2008). 8 Kimura, T., Nakata, T. TL 48, 43 (2007). 9 Duffy, L.A., Matsubara, H., Proctor, D.J. JACS 130, 1136 (2008). 10 Li, J., Li, S., Jia, X. SL 1529 (2008). 11 Molander, G.A., Czako, B., Rheam, M. JOC 72, 1755 (2007). 12 Inui, M., Nakazaki, A., Kobayashi, S. OL 9, 469 (2007). 13 Aulenta, F., Berndt, M., Bru¨dgam, I., Hartl, H., So¨rgel, S., Reissig, H.-U. CEJ 13, 6047 (2007). 14 Wu, Y., Gao, J. OL 10, 1533 (2008). 15 Ankner, T., Hilmersson, G. TL 48, 5707 (2007). 16 Zriba, R., Bezzenine-Lafollee, S., Guibe, F., Magnier-Bouvier, C. TL 48, 8234 (2007).

Samarium(III) triﬂate. Friedel– Crafts reaction.1 Activation by Sm(OTf)3 an electrophilic halogenating agent attacks alkenes and thereby gravitating the alkylation of arenes.

R

R'

Ar

Sm(OTf)3

+

ArH

NBS or I2 MeCN

R'

R X

1

Hajra, S., Maji, B., Bar, S. OL 9, 2783 (2007).

Scandium(III) ﬂuoride. Hydroxymethylation.1 A new catalyst for hydroxymethylation (with HCHO) of dimethylsiloxyalkenes is ScF3. The reaction is performed at room temperature in THF– H2O (9 : 1).1 1

Kokubo, M., Kobayashi, S. SL 1562 (2008).

Scandium(III) triﬂate. Ring cleavage. Catalyzed by Sc(OTf)3, alcoholysis of epoxides1 and aziridines2 proceeds at room temperature. The ring opening of meso-epoxides is rendered asymmetric if a chiral ligand such as 1 is added to the reaction medium.1 Lactones give polymers via alcoholysis.3

N OH

N HO

(1) (Z)-Chloroalkenes. Ketones are stereoselectively converted into (Z)-chloroalkenes by PhCOCl using Sc(OTf)3 as catalyst. Cyanuric chloride is the chloride source and dehydrating agent (for reverting PhCOOH into PhCOCl).4

408

Scandium(III) triﬂate

+

R'

R

Cl

Sc(OTf)3

O PhCOCl

DMF EtOAc Δ

R'

R

Substitution. Introduction of a CZS bond at an a-position of a diketopiperazine by replacement of an acetoxy group is achieved in a reaction catalyzed by Sc(OTf)3 using MeCN as solvent, which is critical.5 OAc N O

OAc

OAc O

Sc(OTf)3

NMe

H2S/MeCN

N O

OAc

OAc

SH O

O2

O

N

NMe

S

S

NMe

O SH

Mannich reaction. When mixed with Sc(OTf)3 an ArNH2, ethyl glyoxylate, and an enol ester assemble to give a g-keto-N-aryl-a-amino acid ester.6 The Mannich reaction of ketene O,S-acetals can give rise to b-lactams.7 Reaction with enol esters proceeds reasonably well, and that involving ArNH2, ethyl glyoxylate and vinyl acetate gives quinoline-2-carboxylic esters.8 R

R

R' +

TBSO

S

N

N

ArNH2 + R

N

25o

PMP

Sc(OTf)3

CHO COOEt

R'

Sc(OTf)3

O

Ar

H N

COOEt N

O

MeCN 25o

OAc

PMP

COOEt R=H

R = Me

Michael reaction. (Z )-Enones are synthesized from siloxyallenes by reaction with alkylidenemalonic esters under mild conditions.9 The broad scope of the reaction makes these synthetically valuable polyfunctional products readily available. O OSiX3 R

C

+ MeO R'

R"

O

O OMe

Sc(OTf)3 MeCN CF3CH2OH

R"

O OMe

R R'

O

OMe

(Z : E 20 : 1)

Scandium(III) triﬂate

409

A highly signiﬁcant functionalization of cycloalkenes, including cyclobutene, indene, dihydrofurans, at the sp 2-carbon atom(s) via dinitrosation and coordination to cobalt, and Michael reaction is terminated by decomposition of the adducts by an exchange reaction. Activation of the Michael acceptors by Sc(OTf)3 gives the best result, in the presence of a strong base such as (Me3Si)2NLi.10 O N Co-Cp* N O

Cp*Co(CO)2 NO

O N Co-Cp* N E O E

Sc(OTf)3 LiHMDS [E+]

[E+] = Michael acceptor

E E

a-Hydroxyalkyl-g-lactams. Cyclopropanecarboxamides undergo ring opening in the presence of Sc(OTf)3, NaI and Me3SiCl. The resulting ketene O,N-acetal complexes bearing an iodoethyl chain are reactive toward RCHO as aldol donors. Adducts are readily formed and in turn they cyclize to afford g-lactams with high diastereoselectivity.11

O

O

O R

Ph

N H

Sc(OTf)3, Me3SiCl, NaI;

Ph

O R

N

OH

Et3N; HCl

R' + R'CHO dr; up to 94 : 6

Cycloaddition. Aldimines and those prepared in situ combine with ethyl propynoate readily. On applying the reaction to arylamines several quinoline-3-carboxylic esters have been prepared.12 The formation of 1,4-dihydropyridine-3,5-dicarboxylic esters13 involves electrocyclic opening of the 1 : 1-cycloadducts and a Diels–Alder reaction.

COOEt

R + NR'

Sc(OTf)3 PhMe Δ

R

E

R'N E = COOEt

R

R E R'N

E

E N R'

410

Silica gel

Cycloisomerization. 2-(4-Pentynyl)furan undergo ring closure to afford a bicyclic isomer in 80% yield.14 The catalyst system contains Hg(OAc)2 and 0.1 mol% of Sc(OTf)3. Because using Hg(OTf)2 alone gives the product only in a low yield, it is interesting to ﬁnd out whether Hg(OTf)OAc is a particularly active catalyst. O

O

Sc(OTf)3 Hg(OAc)2 MeCN

Nazarov cyclization onto a heteroaromatic nucleus employs Sc(OTf)3 (5 mol%) and LiClO4 (1 equiv.) in hot dichloroethane.15 Transesteriﬁcation. Because of its Lewis acidity, Sc(OTf)3 catalyzes transesteriﬁcation.16 1

Tscho¨p, A., Marx, A., Sreekanth, A.R., Schneider, C. EJOC 2318 (2007). Peruncheralathan, S., Henze, M., Schneider, C. SL 2289 (2007). 3 Nomura, N., Taira, A., Nakase, A., Tomioka, T., Okada, M. T 63, 8478 (2007). 4 Su, W., Jin, C. OL 9, 993 (2007). 5 Overman, L.E., Sato, T. OL 9, 5267 (2007). 6 Isambert, N., Cruz, M., Arevalo, M.J., Gomez, E., Lavilla, R. OL 9, 4199 (2007). 7 Benaglia, M., Cozzi, F., Puglisi, A. EJOC 2865 (2007). 8 Isambert, N., Cruz, M., Arevalo, M.J., Gomez, E., Lavilla, R. OL 9, 4199 (2007). 9 Reynolds, T.E., Binkley, M.S., Scheidt, K.A. OL 10, 2449 (2008). 10 Schomaker, J.M., Boyd, W.C., Stewart, I.C., Toste, F.D., Bergman, R.G. JACS 130, 3777 (2008). 11 Wiedemann, S.H., Noda, H., Harada, S., Matsunaga, S., Shibasaki, M. OL 10, 1661 (2008). 12 Kikuchi, S., Iwai, M., Fukuzawa, S. SL 2639 (2007). 13 Kikuchi, S., Iwai, M., Murayama, H., Fukuzawa, S. TL 49, 114 (2008). 14 Yamamoto, H., Sasaki, I., Imagawa, H., Nishizawa, M. OL 9, 1399 (2007). 15 Malona, J.A., Colbourne, J.M., Frontier, A.J. OL 8, 5661 (2006). 16 Remme, N., Koschek, K., Schneider, C. SL 491 (2007). 2

Silica gel. Isomerization. On exposure to silica gel 1-alkenylcyclopropyl sulfonates are converted into extended allyl sulfonates.1 Such products can be used to synthesize amines, among numerous other functional molecules. O

SO2R SiO2

n

O n

SO2R

Catalyst support. A review of the chemistry that employs silica-supported catalysts for the Heck reaction2 and a report on development of a diphosphine ligand linked to mesoporous silica MCM-41 for PdCl2 (with CuI to promote the Sonogashira coupling3) have appeared.

Silver ﬂuoride

411

Perchloric acid supported on silica is a useful catalyst for carbamoylation of alcohols and phenols under solvent-free conditions (ROH þ NaOCN),4 and sulfuric acid on silica catalyzes formation of imides from nitriles and acid anhydrides.5 Molybdenum imido alkylidene catalysts supported by silica gel remain stable and highly active for alkene metathesis.6 Friedel– Crafts reaction. An intramolecular alkylation with an N-tosylaziridine unit as electrophile is apparently favored by entropic and stereochemical factors. Thus heating with SiO2 at 1208 accomplishes this feat.7 OTBS

OTBS O O

O SiO2

NHTs

N Ts

O

O

120o

O O

O

52% 1

Quan, L.G., Lee, H.G., Cha, J.K. OL 9, 4439 (2007). Polshettiwar, V., Molna´r, A. T 63, 6949 (2007). 3 Cai, M., Sha, J., Xu, Q. T 63, 4642 (2007). 4 Modarresi-Alam, A.R., Khamooshi, F., Nasrollahzadeh, M. T 63, 8723 (2007). 5 Habibi, Z., Salehi, P., Zolﬁgol, M.A., Youseﬁ, M. SL 812 (2007). 6 Blanc, F., Thivolle-Cazat, J., Basset, J.-M., Coperet, C., Hock, A.S., Tonzetich, Z.J., Schrock, R.R. JACS 129, 1044 (2007). 7 Collins, J., Drouin, M., Sun, X., Rinner, U., Hudlicky, T. OL 10, 361 (2008). 2

Silver acetate. Cyclocarboxylation.1 Propargylic alcohols add to CO2 in the presence of DBU and the salts of the carbonic acid monoesters rapidly cyclize when AgOAc is present to activate the triple bond. O

OH R" R

R'

AgOAc/CO2

O R

O

DBU, PhMe 25o

R'

R"

1

Yamada, W., Sugawara, Y., Cheng, H.M., Ikeno, T., Yamada, T. EJOC 2604 (2007).

Silver ﬂuoride. Alkynylation. The reaction of 1-alkynes with triﬂuoromethyl ketones in water is promoted by AgF (with ligand Cy3P).1 1

Deng, G.-J., Li, C.-J. SL 1571 (2008).

412

Silver hexaﬂuoroantimonate

Silver hexaﬂuoroantimonate. Cyclopropanation. Cycloaddition involving carbenoids bearing both donor and acceptor substituents is effectively catalyzed by AgSbF6. Alkenes that are reluctant to react with catalysis by Rh2(OAc)4 (e.g., those prefer to undergo CZH insertion or with a sterically hindered double bond) are more susceptible to participate.1 By way of cycloisomerization the formation of a tetracycle containing two cyclopropane units from a 1,5-dien-10-yne is an intriguing transformation, whereas a truncated 1,6-enyne affords a simple alkenylcyclopentene.2

ROOC

H

AgSbF6

ROOC

ClCH2CH2Cl 50°

ROOC

H

ROOC H 66% R'

R'

ROOC ROOC

AgSbF6

ROOC

ClCH2CH2Cl

ROOC

25°

100%

Pyrazoles. N-Propargyl-N-tosyl hydrazones cyclize with migration of the Ts group upon coordination with AgSbF6 to furnish pyrazole derivatives.3

R N Ts N H R'

R

Ts AgSbF6

R"

CH2Cl2

N N

R"

25o

R'

1

Thompson, J.L., Davies, H.M.L. JACS 129, 6090 (2007). Porcel, S., Echavarren, A.M. ACIE 46, 2672 (2007). 3 Lee, Y.T., Chung, Y.K. JOC 73, 4698 (2008). 2

Silver mesylate. Isomerization. Propargylic alcohols are converted into 1,3-transposed conjugated carbonyl compounds with mediation of CO2 and DBU, and catalyzed by AgOMs in formamide

Silver(I) oxide

413

at room temperature.1 The process involves CZO bond cleavage, in contrast to the report of a similar reaction catalyzed by AgOAc (loc. cit.). OH R

R'

O

AgOMs/CO 2 DBU, HCONH 2

R'

R

R"

R'

1

Sugawara, Y., Yamada, W., Yoshida, S., Ikeno, T., Yamada, T. JACS 129, 12902 (2007).

Silver nitrate. Hydroamination. Formation of the N-Boc derivative of 3-vinyl-5-phenylisoxazolidine from an O-alkylhydroylamine that contain a b-allenyl group paves the way toward elaboration of sedamine.1 The intramolecular hydroamination is a high-yielding reaction. O Ph

NHBoc

O

AgNO3 Me2CO, H2O

C

NBoc

OH

Ph

Ph 98%

N H

sedamine

Propargylic amines. To assemble 1-alkynes, aldehydes, and amines into propargylic amines the heating with a AgNO3/zeolite catalyst is a convenient method.2 Oxidative decarboxylation. When a-amido acids suffer degradation to lose CO2, imides are produced. The transformation is mediated by AgNO3, (NH4)2S2O8 and CuSO4 . 5H2O.3 O R

R' N H

O

AgNO3–CuSO 4

COOH

(NH4)2S2O8

R

H2O

R' N H

O

1

Bates, R.W., Nemeth, J.A., Snell, R.H. S 1033 (2008). Maggi, R., Bello, A., Oro, C., Sartori, G., Soldi, L. T 64, 1435 (2008). 3 Huang, W., Wang, M., Yue, H. S 1342 (2008). 2

Silver(I) oxide. Oxidation.1 A combination of Ag2O and pyridine-N-oxide in MeCN can be used to convert benzylic halides into aroic esters and primary allylic halides into enals. Cyclization.2 The modes of Ag(I)-catalyzed cyclization of 2-alkynyl-3-formylquinolines in MeOH have been correlated with the pKa values of the silver salts used. Both 5-exo-dig and 6-endo-dig pathways are equally favored in the presence of AgOAc, products arising from the former pathway predominate in using more basic silver salts (e.g., Ag2O, AgO).

414

Silver perchlorate

OMe

OMe CHO

MeOH

N

O

O

[Ag+]

N

N OMe OMe

MeO

[Ag+] = Ag2O, AgO, Ag 2CO3

AgOTf, AgNO 3, AgSbF6, AgPF6

AgOAc (1 : 1) 1

Chen, D.X., Ho, C.M., Wu, Q.Y.R., Wu, P.R., Wong, F.M., Wu, W. TL 49, 4147 (2008). Godet, T., Vaxelaire, C., Michel, C., Milet, A., Belmont, P. CEJ 13, 5632 (2007).

2

Silver perchlorate. OZH bond insertion.1 It is signiﬁcant that AgClO4 and Rh2(OAc)4 show a regiochemical difference in the trapping of the carbenoid generated from a conjugated a-diazoester by BnOH. N2 Ph

COOMe

OBn

CH2Cl2

COOMe

Ph

+ BnOH

AgClO4 Rh2(OAc)4

OBn

+ Ph

COOMe

>98 : <2 <2 : >98

1

Yue, Y., Wang, Y., Hu, W. TL 48, 3975 (2007).

Silver tetraﬂuoroborate. Nazarov –Friedel-Crafts reaction tandem.1 1-Alkenyl-2,2-dichlorocyclopropyl trialkylsilyl ethers are subject to Nazarov cyclization. If the alkenyl chain is terminated with an aromatic ring at a proper distance, bicyclization becomes a possibility.

O OTIPS

AgBF4 MeCN Δ

63% 1

Grant, T.N., West, F.G. OL 9, 3789 (2007).

Silver triﬂate

415

Silver triﬂate. Dihydroisoquinolines. Aldimines derived from o-alkynylaraldehydes and amines are amenable to cyclize under the inﬂuence of an Ag(I) species (e.g., AgOTf), barring stereochemical inhibition. Accordingly, reduction of the imines facilitates the formation of the heterocyclic compounds.1 Imines bearing an N-methoxycarbonylmethyl group readily generate 1,3-dipolar species and their trapping has been observed.2 R R

AgOTf

+

ArNH2

NAr

proline, 4A-MS EtOH; (NaBH4)

CHO R

R AgOTf

N

COOMe

60o

+

O

N

COOMe

PhMe N

O

R'

R'

Silyl transfer. 1,1-Di(t-butyl)silacyclopropanes readily submit the di-t-butylsilyl residue to a-keto esters to form 4-alkoxy-1,3,2-dioxasiloles. In the case of an allyloxy ester the situation is set up for the Ireland– Claisen rearrangement.3 O O

R HO

O

COOH

AgOTf–25o;

+

HF–Py

R

Si

The silyl transfer to imines delivers silaaziridines that can enter cross-coupling with alkynes to afford alylic amines.4 R NR' R

+

AgOTf

Si

1

R R

Si N R'

Ding, Q., Yu, X., Wu, J. TL 49, 2752 (2008). Su, S., Porco J.A. Jr JACS 129, 7744 (2007). 3 Howard, B.E., Woerpel, K.A. OL 9, 4651 (2007). 4 Nevarez, Z., Woerpel, K.A. OL 9, 3773 (2007). 2

R" (Ph3P)4Pd; t-BuOK, Bu4NF

R R" R

NH R'

416

Sodium borohydride

Sodium borohydride. Reduction. The reduction of a-(benzoxazol-2-ylthio) ketones with NaBH4 gives thiiranes via spirocyclic intermediates.1 N S

MeOH, THF

O R

N

S

NaBH4 /NaOH

O

+

R

R'

OH O

R'

With NaBH4 –Br2 malonic esters are reduced to 1,3-diols.2 N-Alkylation of hydroxyalkylamines is achieved by adding NaBH4 to their premixture with ketones and (i-PrO)4Ti.3 Differences in the stereochemical course for reduction of imines by NaBH4 and Zn(BH4)2, as controlled by a 1,3-related stereogenic center4 is synthetically signiﬁcant. CF3

CF3 Ph

N

Ph

COOK

CF3

+

N H

COOH

NaBH4; H+

Ph

N H

COOH

25 : 1 1 : 21

Zn(BH4)2; H+

Hydrogenation of monosubstituted and 1,2-disubstituted alkenes is accomplishable by NaBH4 and catalytic amounts of RuCl3 . xH2O in aqueous THF.5 1

Yamada, N., Mizuochi, M., Takeda, M., Kawaguchi, H., Morita, H. TL 49, 1166 (2008). Tudge, M., Mashima, H., Savarin, C., Humphrey, C., Davies, I. TL 49, 1041 (2008). 3 Salmi, C., Loncle, C., Letourneux, Y., Brunel, J.M. T 64, 4453 (2008). 4 Hughes, A., Devine, P.N., Naber, J.R., O’shea, P.D., Foster, B.S., McKay, D.J., Volante, R.P. ACIE 46, 1839 (2007). 5 Sharma, P.K., Kumar, S., Kumar, P., Nielsen, P. TL 48, 8704 (2007). 2

Sodium borohydride– dimethyl ditelluride. Elimination. 1,2-Cyclonucleosides are opened on reaction with NaBH4 and catalytic amounts (0.1 equiv.) of MeTeTeMe. If the 3-hydroxyl is acetylated, the tellurides undergo elimination in situ. The corresponding seleno derivatives are stable under similar reaction conditions.1 R'

N

N

RO

R'

O NaBH4 Me2Te2

O

O

AcO 1

AcO

O TeMe

Sheng, J., Hassan, A.E.A., Huang, Z. JOC 73, 3725 (2008).

R'

O

NH

N

RO

O

O

N

RO O

NH O

Sodium periodate

417

Sodium dichloroiodate. Nitrile synthesis.1 A direct method for conversion of aldehydes to nitriles entails reaction with aq. ammonia in the presence of NaICl4. 1

Telvekar, V.N., Patel, K.N., Kundaikar, H.S., Chaudhari, H.K. TL 49, 2213 (2008).

Sodium hydride. Williamson synthesis.1 Ether synthesis from alcohols and RBr (esp. ArCH2Br) is accomplished with NaH in DMF at room temperature. 1

Jin, C.H., Lee, H.Y., Lee, S.H., Kim, I.S., Jung, Y.H. SL 2695 (2007).

Sodium iodide. Reduction.1 Aryl azides are reduced to arylamines by NaI –BF3 . OEt2 in MeCN at room temperature. Henry reaction.2 In the presence of NaI bromonitromethane condenses with aldehydes in THF. The usefulness of the process is noted in the stereoselective assemblage of the anti,anti-isomer of 1-bromo-2-hydroxy-3-dibenzylamino-1-nitrobutane. 1

Kamal, A., Shankaraiah, N., Markandeya, N., Reddy, C.S. SL 1297 (2008). Concellon, J.M., Rodriguez-Solla, H., Concellon, C., Garcia-Garcia, S., Diaz, M.R. OL 8, 5979 (2006).

2

Sodium nitrite. Sandmeyer reaction.1 The arylamine to aryl iodide transformation is accomplished by NaNO2, KI, TsOH in MeCN at 10–258. 1

Krasnokutskaya, E.A., Semenischeva, N.I., Filimonov, V.D., Knochel, P. S 81 (2007).

Sodium periodate. Epoxide cleavage. In aqueous THF or MeCN epoxides are cleaved by NaIO4 as shown by the following example.1 O NaIO4

O

THF, H2O

CHO

91%

N-Oxy radicals. Oxy radicals are readily generated from N-hydroxycarboximides such as N-hydroxyphthalimide by treatment with NaIO4 on wet SiO2.2 1

Binder, C.M., Dixon, D.D., Almaraz, E., Tius, M.A., Singaram, B. TL 49, 2764 (2008). Coseri, S. EJOC 1725 (2007).

2

418

Sodium phenoxide

Sodium phenoxide. Mukaiyama aldol reaction. The base modiﬁed by the phosphine oxide ligand 1 is effective for catalyzing the aldol reaction.1 Ph

Ph

P O

Ph

P O Ph

(1) 1

Hatano, M., Takagi, E., Ishihara, K. OL 9, 4527 (2007).

Sodium tetracarbonylferrate(II). Carbonylative coupling.1 Dibenzyl ketones are obtained in moderate to high yields by the reaction of ArCH2Br with Na2Fe(CO)4 in NMP. If unsymmetrical ketones are required the reaction is performed in two stages: ﬁrst with one bromide at 08, then the second bromide at room temperature. 1

Potter, R.G., Hughes, T.S. OL 9, 1187 (2007).

Sodium tetrachloroaurate. b-Alkoxy enones.1 a-Hydroxypropargyl epoxides undergo interesting transformations on treatment with NaAuCl4 in reﬂuxing benzene. Perhaps an activation of the triple bond to induce attack of the epoxy atom triggers 1,2-rearrangement or CZC bond cleavage. O OH

NaAuCl 4 PhH 80o

R

O

R

R'

O

R'

O R"'

R"'

OH

NaAuCl 4

R" R

O

PhH 80o

O R'

R"

R' R

1-Aminoindolizines. Pyridine-2-carbaldehyde and homologues condense with amines and 1-alkynes in water or under solvent – free conditions to generate 1-aminindolizines.

Sulfamic acid

419

Apparently, the Au salt is responsible for inducing cycloisomerization of the propargylic amines.2

CHO

NR'2

+ R'2NH

N

NaAuCl 4 H2O 60o

N

+ R

R

1

Shu, X.-Z., Liu, X.-Y., Ji, K.-G., Xiao, H.-Q., Liang, Y.-M. CEJ 14, 5282 (2008). Yan, B., Liu, Y. OL 9, 4323 (2007).

2

Sodium tetrakis[3,5-bis(triﬂuoromethyl)phenyl]borate. Deacetalization.1 A colloidal suspension of the title compound in water is capable of hydrolyzing acetals. 1

Chang, C.-C., Liao, B.-S., Liu, S.-T. SL 283 (2007).

Sodium tetramethoxyborate. Michael reaction. Conjugate addition involving stabilized C-nucleophiles is readily achieved using NaB(OMe)4 [3 mol%] as catalyst in MeCN.1 1

Campana, A.G., Fuentes, N., Gomez-Bengoa, E., Mateo, C., Oltra, J.E., Echavarren, A.M., Cuerva, J.M. JOC 72, 8127 (2007).

Strontium. Ketones.1 Treatment of sodium carboxylates (from RCOOH þ NaH) with Sr gives species that react with MeI to afford methyl ketones. Scope and mechanism of this reaction has yet to be established. 1

Miyoshi, N., Matsuo, T., Asaoka, M., Matsui, A., Wada, M. CL 36, 28 (2007).

Sulfamic acid. t-Butyl carbamates. For derivatization of amines with t-Boc2O at room temperature without any solvent, ultrasound irradiation enhances the catalysis of sulfamic acid.1 1

Upadhyaya, D.J., Barge, A., Stefania, R., Cravotto, G. TL 48, 8318 (2007).

420

Sulfur

Sulfur. Reduction.1 Nitroarenes are reduced to the corresponding amines by sulfur – NaHCO3 (3 equiv. each) in DMF at 1308. 1

McLaughlin, M.A., Barnes, D.M. TL 47, 9095 (2006).

Sulfuric acid. Porphyrin.1 Access to the parent macroheterocycle (in 77% yield) is facilitated by heating the readily available meso-tetrakis(hexyloxycarbonyl) derivative with sulfuric acid containing some water at 1808. 1

Neya, S., Quan, J., Hata, M., Hoshino, T., Funasaki, N. TL 47, 8731 (2006).

T Tantalum(V) dimethylamide. Aminoalkylation.1 The a-carbon of an N-alkylarylamine is activated by Ta(NMe2)5 such that it adds to simple alkenes. R Ar-NHMe

+ R'

Ph

(Me2N)5Ta

Ar

N H R

PhMe 160–165°

R'

(Me2N)5Ta

N H

PhMe 160 –165°

Ph

N H

1

Herzon, S.B., Hartwig, J.F. JACS 129, 6690 (2007).

Tellerium chloride. Preparation. The title reagent can be prepared by heating Te(0) in sulfuryl chloride.1 1

Petragnani, N., Mendes, S.R., Silveira, C.C. TL 49, 2371 (2008).

Tetrabenzyl pyrophosphate. Amide formation. As a dehydrating agent [(BnO)2PO]2O is active in condensing RCOOH and amines. The reaction is carried out in chloroform and also with catalytic quantities of DMAP.1 1

Reddy, Y.T., Reddy, P.N., Reddy, P.R., Crooks, P.A. CL 37, 528 (2008).

Tetrabutylammonium dichloroiodate. Iodination. In providing electrophilic iodine, Bu4NICl2 in sulfuric acid constitutes another reagent system for nuclear iodination arenes.1 1

Filimonov, V.D., Semenischeva, M., Krasnokutskaya, E.A., Hwang, H.Y., Chi, K.-W. S 401 (2008).

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 421

422

Tetrabutylammonium ﬂuoride, TBAF

Tetrabutylammonium ﬂuoride, TBAF. Substitution. Activated aryl ﬂuorides are converted into ethers on reaction with various alcohols released from (RO)4Si in situ by TBAF. The reaction is conducted in reﬂuxing acetone.1 Elimination. 2-Bromo-1-alkenes undergo dehydrobromination on warming with TBAF in DMF at 608.2 1,1-Dicyanoalkyl silyl ethers are converted into acyl cyanides by TBAF. Esters and amides are readily formed therefrom.3 Generation of sulfenate anion is convenient from RS(¼O)CH2CH2SiMe3.4 Two interchangeable ﬂuoride ion sources used in aryne generation from o-trimethylsilylaryl triﬂates are CsF and TBAF. Many benzannulated heterocycles are now conveniently prepared via cycloaddition reactions of arynes. 3-Indazolecarboxylic esters are accessible from such a reaction.5 Alkylation. A synthetic approach to platensimycin entails a step of intramolecular alkylation, in which a phenolate intermediate is generated from a silyl ether. The process can be accomplished with Bu4NF.6

Br

O

O

Bu4NF THF 130o

OTIPS

O 88%

For hydroxyalkylation of 2-ﬂuoro-3-alkynoic esters the amount of TBAF, which is used as base, affects the reaction pathway. Kinetic control and thermodynamic control are observed in the reactions where substoichiometric (e.g., 0.2 equiv.) and excess of TBAF are present, respectively.7

C6H13

C6H13

F

F

THF

COOEt

0o

Ar

COOEt OH

+

F

C

C6H13 Ar

COOEt

OH

+ ArCHO Bu4NF (0.2 equiv.)

70%

3%

Bu4NF (2.0 equiv.)

–

83%

To render a g,d-unsaturated b-ketolactone in the enolate form by TBAF is critical for realizing an intramolecular Diels–Alder reaction en route to salvinorin-A.8

Tetrabutylammonium tricarbonyl(nitroso)ferrate

423

O O O BOMO O

H O

O

Bu4NF –78° ~ 5°

BOMO

H

H O salvinorin–A O

O CH(OMe)2

CH(OMe)2 99%

Deprotection. Aldehydes protected as a-trichloromethylalkyl TBS ethers by reaction with TBS-Cl and Cl3CCOONa are recovered by treatment with TBAF in DMF.9 1

Wang, T., Love, J.A. S 2237 (2007). Okutani, M., Mori, Y. TL 48, 6856 (2007). 3 Nemoto, H., Moriguchi, H., Ma, R., Kawamura, T., Kamiya, M., Shibuya, M. TA 18, 383 (2007). 4 Foucoin, F., Caupene, C., Lohier, J.-F., de Oliveira Santos, J.S., Perrio, S., Metzner, P. S 1315 (2007). 5 Liu, Z., Shi, F., Martinez, P.D.G., Raminelli, C., Larock, R.C. JOC 73, 219 (2008). 6 Lalic, G., Corey, E.J. OL 9, 4921 (2007). 7 Xu, B., Hammond, G.B. ACIE 47, 689 (2008). 8 Scheerer, J.R., Lawrence, J.F., Wang, G.C., Evans, D.A. JACS 129, 8968 (2007). 9 Caﬁero, L.R., Snowden, T.S. TL 49, 2844 (2008). 2

Tetrabutylammonium iodide. Halogenation.1 Results of the stereoselective addition of [I/Cl] to a wider range of alkynes based on Bu4NI in reﬂuxing 1,2-dichloroethane have been obtained. Under the same reaction conditions alkenes give vic-dichloroalkanes. 1

Ho, M.L., Flynn, A.B., Ogilvie, W.W. JOC 72, 977 (2007).

Tetrabutylammonium phenolate. 1,3-Dithian-2-yl anion. An exceptionally mild base (compared to BuLi) for desilylative generation of the 1,3-dithian-2-yl anion is Bu4NOPh.1 1

Michida, M., Mukaiyama, T. CL 37, 26 (2008).

Tetrabutylammonium tricarbonyl(nitroso)ferrate. Allylic substitution. More detailed studies on the reaction of allylic carbonates with active methylene compounds1 have revealed mechanistic dichotomy that is liganddependent.1

424

Tetrabutylammonium triphenyldiﬂuorosilicate

O

O

O + O

O

CH(COOtBu)2 O

CH(COOtBu)2

+

O

Bu4N[Fe(CO) 3(NO)]

ligand:

N

N

91

: 9

N

10

:

.. N

90

..

Transesteriﬁcation. Phenyl esters, enol esters, and carbonates undergo transesteriﬁcation on heating with various alcohols and Bu4N[Fe(CO)3(NO)] in hexane.2 1

Plietker, B., Dieskau, A., Mo¨ws, K., Jatsch, A. ACIE 47, 198 (2008). Magens, S., Ertelt, M., Jatsch, A., Plietker, B. OL 10, 53 (2008).

2

Tetrabutylammonium triphenyldiﬂuorosilicate. Benzyne generation. As a ﬂuoride source for initiating the generation of benzyne from 2-trimethylsilylphenyl triﬂate, the effectiveness of Bu4N(Ph3SiF2) is obvious. New possibilities for cycloaddition with enamides leading to indolines and isoquinoline derivatives have been explored.1

COOMe BocHN

E SiMe3

N Boc

Bu4N[Ph3SiF2]

OTf

N AcNH COOMe

E

1

Gilmore, C.D., Allan, K.M., Stoltz, B.M. JACS 130, 1558 (2008).

Tetracarbonylhydridocobalt. Cyclocarbonylation.1 Epoxides bearing a b-hydroxyalkyl substituent are shown to form d-lactones, while catalyzed by HCo(CO)4.

meso-Tetrakis(4-chlorophenylporphyrinato)aluminum tetracarbonylcobaltate

R R

OH O

+

CO

R

HCo(CO)4

O

425

O

R

1

Kramer, J.W., Joh, D.Y., Coates, G.W. OL 9, 5581 (2007).

Tetrachloroauric acid. Biaryls.1 Oxidative dimerization of nonactivated arenes is accomplished with the treatment of PhI(OAc)2 in HOAc, and catalyzed by HAuCl4. Carbonylation.2 A solid catalyst made from HAuCl4 and an ion-exchange resin is used to convert ArNH2 into ArNHCOOMe in MeOH. It can also be used to form ureas from R2NH, CO2 (or CO and O2). g-Keto esters. Acetates of diethynyl carbinols are transformed into g-keto esters (or lactones) with HAuCl4 . 3H2O in alcoholic solvents.3

HAuCl 4

R OAc

R'OH 60o

O + R

COOR'

O R

O

1

Kar, A., Mangu, N., Kaiser, H.M., Beller, M., Tse, M.K. CC 386 (2008). Shi, F., Zhang, Q., Ma, Y., He, Y., Deng, Y. JACS 127, 4182 (2005). 3 Kato, K., Teraguchi, R., Kusakabe, T., Motodate, S., Yamamura, S., Mochinda, T., Akita, H. SL 63 (2007). 2

1,1,2,2-Tetraﬂuoroethanesulfonyl chloride. Aryl tetraﬂates.1 The title reagent is prepared from tetraﬂuoroethene. It is used to derivatize phenols to provide products with higher stability than the corresponding triﬂates. The tetraﬂates are useful for coupling. 1

Rostovtsev, V.V., Bryman, L.M., Junk, C.P., Harmer, M.A., Carcani, L.G. JOC 73, 711 (2008).

Tetrakis[chloro(pentamethylcyclopentadienyl)ruthenium(I)]. Cycloaddition. The title complex is found useful as catalyst for the cycloaddition of organoazides to 1-alkynes to form 1,5-disubstituted 1,2,3-triazoles.1 1

Rasmussen, L.K., Boren, B.C., Fokin, V.V. OL 9, 5337 (2007).

meso-Tetrakis(4-chlorophenylporphyrinato)aluminum tetracarbonylcobaltate. Carbonylation.1 The title reagent (as THF complex) mediates carbonylation of monosubstituted and 2,3-disubstituted epoxides to give succinic anhydrides (22 examples, 90–99% conversion). 1

Rowley, J.M., Lobkovsky, E.B., Coates, G.W. JACS 129, 4948 (2007).

426

1,1,3,3-Tetrakis(triﬂuoromethanesulfonyl)propane

1,1,3,3-Tetrakis(triﬂuoromethanesulfonyl)propane. Michael reaction.1 This carbon acid (1) is highly effective for inducing the Michael reaction between 2-siloxyfurans and enones.

O

O

O

O S

S

CF3 F3C O S O S O CF F3C O 3

(1) 1

Takahashi, A., Yanai, H., Taguchi, T. CC 2385 (2008).

Tetrakis(triethylphosphite)nickel(0). Substitution. The title complex catalyzes retentive substitution of allylic esters with regard to regiochemical and stereochemical senses.1

OAr

OAc R

+

ArOH

NaH, [(EtO)3P]4Ni THF, DMF 50 o

R

1

Yatsumonji, Y., Ishida, Y., Tsubouchi, A., Takeda, T. OL 9, 4603 (2007).

Tetrakis(triphenylphosphine)nickel(0). Coupling reactions. Benzyl ketones and arylacetic acid derivatives of the type ArCH(R)COY are prepared from RCH(X)COY by coupling with ArB(OH)2 using (Ph3P)4Ni as catalyst.1 1

Liu, C., He, C., Shi, W., Chen, M., Lei, A. OL 9, 5601 (2007).

Tetrakis(triphenylphosphine)palladium(0). Coupling reactions. There is a review on Suzuki coupling based on (Ph3P)4Pd (and other Pd species) with certain concessions such as involving unusual reaction partners, ligandless conditions, catalyst on solid-support, in supercritical CO2, H2O, ionic liquids, ﬂuorous media or micelles, being assisted by microwaves or conducted in microreactors or ballmills.1 The involvement of a Merriﬁeld resin-linked phosphine ligand is beneﬁcial to Suzuki coupling of ArCl, in terms of catalyst recovery.2

Tetrakis(triphenylphosphine)palladium(0)

427

Homologative functionalization of alkenes via hydroboration (with 9-BBN) and coupling with carbamoyl chlorides under basic conditions yields carboxamides.3 Arylcyclopropanes are obtained from a Pd-catalyzed reaction of tricyclopropylbismuth and ArX.4 a-Bromoalkyl sulfoxides couple with ArB(OH)2 with inversion of conﬁguration occuring in the oxidative oxidation step (retention of conﬁguration while the Pd-containing intermediates undergo reductive elimination). Of particular signiﬁcance is that the (RS,RS)-diastereomers fail the coupling.5

O S

O

Br

S +

Ph

(Ph3P)4Pd

PhB(OH)2

Na2CO3 H2O, MeOH

Thiolactams enter Suzuki coupling6 and Sonogashira coupling7 with loss of the sulfur atom when copper(I) 2-thienylcarboxylate is also present.

R' +

O

S HN

R'

R

O

(Ph3P)4Pd

R

N

CuI, S

COOCu

Et3N

Coupling of ArB(OH)2 with Ar30 Sb(OAc)2 does not require a base.8 In copper-free Sonogashira coupling the competition of ligand and amine base determines the reaction mechanism.9 The oxidative addition of ArI with (Ph3P)4Pd is faster when amine is present. With the proposed mechanisms the efﬁciency of Ph3P . Ph3As is explained. Diaryltetramethyldisiloxanes surrender the aryl groups for coupling with Ar0 X in reﬂuxing THF to give biaryls.10 This reaction also requires stoichiometric Ag2O and catalytic amounts of TBAF, in addition to (Ph3P)4Pd. A coupling route to 1,3-diaryl-1,2-propadienes is demonstrated by the reaction of a-phenylpropargyl carbonates with ArB(OH)2. The use of mixed carbonate esters for coupling, instead of acetates and benzoates, are important to give good yields, and in the asymmetric version, high ee.11 With an oxidant (benzoquinone) added, a-diazoalkanoic esters and a-diazoketones couple with ArB(OH)2, providing a-aryl-a,b-unsaturated esters and enones, respectively.12 On the other hand, diazoacetic esters are arylated and alkenylated.13

428

Tetrakis(triphenylphosphine)palladium(0)

ArB(OH)2

(Ph3P)4Pd

+

benzoquinone i-Pr2NH, PhMe 80o

N2

R

COOR

+

(Ph3P)4Pd

N2

I

ArI

COOEt

Bu4NBr, Et 3N Me2CO, 35 o

+

Ar

COOR

R N2

COOEt

Ar

O

N2

COOEt

(Ph3P)4Pd/CO

N2

COOEt

DBU, MeCN

Heterocycle synthesis. In the presence of HCOONa and with microwave irradiation Heck reaction of N-alkynoyl-2-(o-bromoaryl)ethylamines cyclize to give benzazepine derivatives. Benzannulated eight-membered lactam homologues are also accessible by the method.14

NR Br

O

(Ph3P)4Pd

NR

HCOONa w

R'

O R'

Formation of dihydroquinol-4-ones from 3-(o-iodoarylamino)propanoate esters involving arylpalladium intermediates which may exist in the palladacycle form and thereby derive special activity for intramolecular attack on the ester group.15 Under similar conditions, ﬁve-membered ring oxime derivatives are prepared.16 O I R N Me

(Ph3P)4Pd

COOMe

R

K3PO4, Et3N PhMe, 110o

N Me

NOR X Z Z = O, NTs

(Ph3P)4Pd

NOR

K2CO3 dioxane, 100 o

Z

Tetrakis(triphenylphosphine)palladium(0)

429

Allenylpalladium compounds are generated from arylpropargyl derivatives, and they behave electrophilically toward nucleophiles. With involvement of such products in intermolecular coupling the synthetic potential of the catalyst is enhanced.17 COOEt CH(COOEt)2

COOEt

(Ph3P)4Pd Cs2CO3

OR

C

DMF, 100 o

4-Aryltetrahydropyridines are synthesized from homopropargylamines and allenylethylamines via coupling with ArB(OH)2. The products are isomeric at the position of the double bond.18 Ar +

HCHO

+

ArB(OH)2

(Ph3P)4Pd THF 50o

NHBn

N Bn

C

Ar HCHO

+

+

ArB(OH)2

(Ph3P)4Pd THF 50o

N Bn

NHBn

Cleavage of CZO bonds. Allylic ethers are cleaved at room temperature in the presence of (Ph3P)4Pd. Rates are much higher in protic solvents (MeOH vs. THF) and the cleavage of allyl, methallyl, prenyl groups in succession is possible.19 Diallyl malonate esters containing an a-aryl substituent (critical!) undergo decarboxylation to give the allyl 4-pentenoates.20 2,3-Alkadienyl 2-alkynoates also decarboxylate, but during the reunion the allenyl and alkynyl fragments are transposed.21 R R C

O

R'

R'

(Ph3P)4Pd PhMe 100o

O

R" R" 38–99%

In principle, 5-vinyl-2-oxazolidinones are accessible from decomposition of 4-amino-2butenyl carbonates, with loss of the nonallylic alcohol only. Trapping of the released CO2 is indeed feasible, although efﬁciency is not sufﬁciently high. The heterocyclic products are obtained in much higher yield by conducting the reaction under a CO2 atmosphere.22

430

Tetrakis(triphenylphosphine)palladium(0)

O O

H N

Bn

O

R

O

(Ph3P)4Pd

OMe

BnN

DBU MeCN 50o

R

R

R

Trapping the oxy anion from the Pd-induced ring-opening of a g,d-epoxy-a,b-unsaturated ester with triphenyl borate provides allylpalladium species for eventual reaction with nucleophiles. syn-3-Alkoxy-4-hydroxy-2-alkenoic esters are readily formed.23 O

COOEt

R

OH (Ph3P)4Pd

COOEt

R

BnOH, THF

+ (PhO)3B

0o

OPh

Reductive removal of a triﬂoxy substituent without affecting an aromatic bromide is important in accessing a precursor for gelsemine synthesis. This can be done by a reaction with Bu3SnH, catalyzed by (Ph3P)4Pd.24 EtOOC

EtOOC (Ph3P)4Pd

OTf

MeO

MeO

Bu3SnH

OMe

O

LiCl/THF 23o

N H

OMe

Br

O

N H

Br

Allyl 2-pyridylacetates is induced to decarboxylate by (Ph3P)4Pd. N-Allylpyridinium salts and N-allyl-2-alkylidene-1,2-dihydropyridines are implicated as reaction intermediates.25 Cyclization. Synthetic exploitation of reactivities of p-allylpalladium complexes that are generated from propargylic26 and allenic derivatives27 is shown by the closure of two azacycles in one step. ArSO2 NH

NHSO2Ar

(Ph3P)4Pd

ArSO2 N

NaH, MeOH 60o

Br

N SO2Ar OMe

C H N O

S

Br NHBn O

(Ph3P)4Pd NaH, MeOH

NBn N S O O 57%

+

NHBn N S O O 12%

Tetrakis(triphenylphosphine)palladium(0)

431

Cyclization attendant by coupling from molecules containing both an amino group and an allene unit has apparent utility in synthesis.28 Formation of ﬁve- or six-membered rings is subject to change of the substituent pattern of the allene moiety. The bond distance between the nitrogen atom and the unsaturation is of necessity important. Diazetidines have been acquired from 4-hydrazinyl-1,2-alkadienes.29 R

R

K2CO3 /DMF 70o

+ ArI

TsN

N Bz (low yields)

R'

X = Ts

R

R

C

Ar

(Ph3P)4Pd

R' HN Ts

R'

R

(Ph3P)4Pd

R' HN X

Ar

Ar

C

TsN

K2CO3 /PhMe 100o

R'

+ ArI

A p-allylpalladium complex derived from coupling of an allene with ArB(OH)2 is reactive toward an aldehyde, therefore formation of cyclic alcohols from 4,5-hexadienal, 5,6-heptadienal and various analogues, in different degrees of efﬁciency, is expected.30 Ar C +

ArB(OH)2

(Ph3P)4Pd MeOH w

CHO

OH 78% Ar

C +

TsN

(Ph3P)4Pd

ArB(OH)2

TsN

MeOH w

CHO

OH 23%

Intramolecular trapping of p-allylpalladium species by enamine to form 2-vinylcyclopentanecarbaldehydes or cyclohexanecarbaldehydes is efﬁcient.31 Br

CHO

CHO (Ph3P)4Pd Et3N,

BnO OTBS

NH

THF 25o

BnO OTBS 95%

432

Tetrakis(triphenylphosphine)palladium(0)

In HCOOH the treatment of molecules containing diyne and enal subunits with (Ph3P)4Pd leads to extensive structural reorganization, a furan ring is created in the process.32

Z

CHO Z

O (Ph3P)4Pd HCOOH dioxane 80 o

Z = O, NTs, CR 2

Different reaction patterns are manifested33 when Meldrum acid that is substituted with a cinnamyl ester is exposed to (Ph3P)4Pd and a mixture of (PhCN)2PdCl2 –Yb(OTf)3. O (Ph3P)4Pd

O

O

O

R'OOC

R'OH/THF 40–60°

O Ar

O OR

Ar

O

(PhCN)2PdCl2

R= Ac, COOEt

O

Yb(OTf)3 THF

O O

Ar

Intramolecular Heck-type reaction initiated by palladation of alkenyl triﬂates to generate 1,2-dimethylenecyclobutanes has been accomplished. Carbonylation of the cyclic intermediates occurs under CO.34 Ph

Ph Ph

OTf

(Ph3P)4Pd

Ph

Ar/Et 3N MeOH, DMF

OTf

(Ph3P)4Pd CO/Et 3N

COOMe

MeOH, DMF

Highly strained ring systems can be generated from a tandem Heck reaction sequence. This achievement attests to the value of the synthetic method.35

Tetrakis(triphenylphosphine)palladium(0)

O

433

O

O SiMe3

Br

O

(Ph3P)4Pd

SiMe3

i-Pr2NH PhH w

66% O O

SiMe3 [Pd]

Cycloaddition. A new trapping partner for the trimethylene-palladium complex is carbon dioxide. 3-Methyl-2-buten-4-olide is formed.36 N,N 0 -Di-t-butyl-1,2-diaziridinone behaves as a 1,3-dipolar species in the presence of (Ph3P)4Pd and such is trapped by alkenes.37 O

O N N

R

(Ph3P)4Pd

+

N

N

65o

R R'

R'

Aminocarbonylation. A polymer-supported (Ph3P)4Pd catalyzes aminocarbonylation of haloarenecarboxylic acids (with CO and primary or secondary amines) in a ﬂow reactor. Surprisingly, better results than batch process are obtained.38 1

Alonso, F., Beletskaya, I.P., Yus, M. T 64, 3047 (2008). Schweizer, S., Becht, J.-M., Le Drian, C. OL 9, 3777 (2007). 3 Yasui, Y., Tsuchida, S., Miyabe, H., Takemoto, Y. JOC 72, 5898 (2007). 4 Gagnon, A., Duplessis, M., Alsabeh, P., Barabe, F. JOC 73, 3604 (2008). 5 Rodriguez, N., de Arellano, C.R., Asensio, G., Medio-Simon, M. CEJ 13, 4223 (2007). 6 Prokopcova, H., Kappe, C.O. JOC 72, 4440 (2007). 7 Silva, S., Sylla, B., Suzenet, F., Tatibouet, A., Rauter, A.P., Rollin, P. OL 10, 853 (2008). 8 Yasuike, S., Qin, W., Sugawara, Y., Kurita, J. TL 48, 721 (2007). 9 Tougerti, A., Negri, S., Jutand, A. CEJ 13, 666 (2007). 10 Napier, S., Marcuccio, S.M., Tye, H., Whittaker, M. TL 49, 3939 (2008). 11 Yoshida, M., Okada, T., Shishido, K. T 63, 6996 (2007). 12 Peng, C., Wang, Y., Wang, J. JACS 130, 1566 (2008). 13 Peng, C., Cheng, J., Wang, J. JACS 129, 8708 (2007). 14 Idonets, P.A., Van dr Eycken, E.V. OL 9, 3017 (2007). 15 Sole, D., Serrano, O. ACIE 46, 7270 (2007). 16 Ohno, H., Aso, A., Kadoh, Y., Fujii, N., Tanaka, T. ACIE 46, 6325 (2007). 17 Bi, H.-P., Liu, X.-Y., Gou, F.-R., Guo, L.-N., Duan, X.-H., Shu, X.-Z., Liang, Y.-M. ACIE 46, 7068 (2007). 18 Tsukamoto, H., Kondo, Y. ACIE 47, 4851 (2008). 19 Tsukamoto, H., Suzuki, Y., Kondo, Y. SL 3131 (2007). 2

434

Tetrakis(triphenylphosphine)platinum(0)

20

Ohta, T., Ito, Y. JOC 72, 1652 (2007). Sim, S.H., Park, H.-J., Lee, S.I., Chung, Y.K. OL 10, 433 (2008). 22 Yoshida, M., Ohsawa, Y., Sugimoto, K., Tokuyama, H., Ihara, M. TL 48, 8678 (2007). 23 Yu, X.-Q., Yoshimura, F., Ito, F., Sasaki, M., Hirai, A., Tanino, K., Miyashita, M. ACIE 47, 750 (2008). 24 Grecian, S., Aube, J. OL 9, 3153 (2007). 25 Waetzig, S.R., Tunge, J.A. JACS 129, 4138 (2007). 26 Ohno, H., Okano, A., Kosaka, S., Tsukamoto, K., Ohata, M., Ishihara, K., Maeda, H., Tanaka, T., Fujii, N. OL 10, 1171 (2008). 27 Hamaguchi, H., Kosaka, S., Ohno, H., Fujii, N., Tanaka, T. CEJ 13, 1692 (2007). 28 Ma, S., Yu, F., Li, J., Gao, W. CEJ 13, 247 (2007). 29 Cheng, X., Ma, S. ACIE 47, 4581 (2008). 30 Tsukamoto, H., Matsumoto, T., Kondo, Y. JACS 130, 388 (2008). 31 Bihelovic, F., Matovic, R., Vulovic, B., Saicic, R.N. OL 9, 5063 (2007). 32 Oh, C.H., Park, H.M., Park, D.I. OL 9, 1191 (2007). 33 Fillion, E., Carret, S., Mercier, L.G., Trepanier, V.E. OL 10, 437 (2008). 34 Innitzer, A., Brecker, L., Mulzer, J. OL 9, 4431 (2007). 35 Blond, G., Bour, C., Salem, B., Suffert, J. OL 10, 1075 (2008). 36 Greco, G.E., Gleason, B.L., Lowery, T.A., Kier, M.J., Hollander, L.B., Gibbs, S.A., Worthy, A.D. OL 9, 3817 (2007). 37 Du, H., Yuan, W., Zhao, B., Shi, Y. JACS 129, 7496 (2007). 38 Csajagi, C., Borcsek, B., Niesz, K., Kovics, I., Szekelyhidi, Z., Bajko, Z., Urge, L., Darvas, F. OL 10, 1589 (2008). 21

Tetrakis(triphenylphosphine)platinum(0). Addition reaction. Stereoselective and regioselective cis-addition of aryl and thio groups from ArCOSAr0 to alkynes by catalysis of (Ph3P)4Pt has been delineated.1 R

R'

(Ph3P)4Pt

+ Ar

xylene 140°

SAr'

R

R'

Ar

SAr'

O 1

Yamashita, F., Kuniyasu, H., Terao, J., Kambe, N. OL 10, 101 (2008).

Tetramethylammonium ﬂuoride. o-Hydroxybenzyl ketones.1 The simultaneous generation of o-quinonemethides from o-siloxybenzyl bromides initiated by desilylation with Me4NF on the one hand, and desilylation of 2-(a-siloxyalkyl)thiazolium salts that gives rise to acyl anion equivalents on the other, caters to the formal substitution of the benzyl bromides. TBSO

R TBSO

Br +

OSiEt3

S

R'

CH2Cl2

R' NMe

1

R

Me4NF

Cl

Mattson, A.E., Scheidt, K.A. JACS 129, 4508 (2007).

O

Tin(IV) chloride

435

2,2,6,6-Tetramethyl-1-oxopiperidine salts. Oxidation. The oxoammonium salts are mild oxidants for converting 2-cycloalkenols to cyclic enones, with 1,3-transposition of the oxygenated site.1 O

N O X

n

n

MeCN, 25o

R

OH R

Under anhydrous conditions it is also possible to utilize the salt to oxidize certain unprotected carbohydrates to aldehydes.2 1

Shibuya, M., Tomizawa, M., Iwabuchi, Y. JOC 73, 4750 (2008). Breton, T., Bashiardes, G., Leger, J.-M., Kokoh, K.B. EJOC 1567 (2007).

2

Thiophosphoryl chloride. Thionation. The carbonyl group of amides and ketones are transformed into the thiono group by reaction with PSCl3 under microwave irradiation.1 1

Pathak, U., Pandey, L.K., Tank, R. JOC 73, 2890 (2008).

Thiosuccinic anhydride and homologues. Diamides. Cyclic thioanhydrides are a source of unsymmetrical diamides. Aminolysis releases a thiocarboylic acid that can be transformed into another amide function on reaction with an N-sulfonyl amine or sulfonyl azide.1 O NHTs NHR

O

O

TsN3

SH NHR

RNH2

S O

O

base Cs2CO3

O O

ArSO2NHR'

NHR' NHR

[Ar = 2,4-(O2N)C6H3]

O 1

Crich, D., Bowers, A.A. OL 9, 5323 (2007).

Tin(IV) chloride. Claisen rearrangement. The aromatic Claisen rearrangement is found to be catalyzed by SnCl4 at room temperature.1

436

Tin(IV) chloride

Fragmentative defunctionalization. b,g-Dioxygenated a-diazo esters undergo fragmentation to give 2-alkynoic esters, in a process that is probably initiated by ionization of the b-hydroxy group.2 N2 HO

COOEt OTBS

COOEt SnCl4

CHO

CH2Cl2 0o

Hetero-Diels– Alder reaction. The condensation of conjugated a-ketoesters with N-alkenyl-2-oxazolidinones shows facial stereodivergence due to the presence of different Lewis acids. For example, stereoisomers are obtained from reactions catalyzed by SnCl4 and by Eu(fod)3.3 R' O

SnCl4 CH2Cl2 –78°

R

O O

N

O

R N

O

COOMe

R' + O

R'

COOMe O

Eu(fod) 3 C6H12

O

R N

O

COOMe

Aromatization.4 Enamines of 6-membered cyclic ketones (cyclohexanone, a-tetralone, b-tetralone, . . .) yield arylamines on treatment with SnCl4 in CH2Cl2 at room temperature. [SbCl5 is less efﬁcient.] Cyclization.5 Efﬁcient cyclization of a polyene initiated from a terminal enol silyl ether shows a remarkable a-selectivity.

SnCl4

Ph Si O

Ph Si O

Ph

Ph 96%

Titanium(IV) chloride

437

Sn-W mixed hydroxide. A white precipitate of the composition Sn19WClO6 . 9H2O, produced by adding SnCl4 . 5H2O to Na2WO4 . 2H2O, catalyzes the mixture of RCHO and NH2OH . HCl to convert into RCN in hot o-xylene.6 1

Sarkar, D., Venkateswaran, R.V. SL 653 (2008). Draghici, C., Brewer, M. JACS 130, 3766 (2008). 3 Gohier, F., Bouhadjera, K., Faye, D., Gaulon, C., Maisonneuve, V., Dujardin, G., Dhal, R. OL 9, 211 (2007). 4 Bigdeli, M.A., Rahmati, A., Abbasi-Ghadim, H., Mahdavinia, G.H. TL 48, 4575 (2007). 5 Uyanik, M., Ishihara, K., Yamamoto, H. OL 8, 5649 (2006). 6 Yamaguchi, K., Fujiwara, H., Ogasawara, Y., Kotani, M., Mizuno, N. ACIE 46, 3922 (2007). 2

Titanium(III) chloride. Conjugated sulfones. Low-valent titanium species are generated from TiCl3, Zn(Pb), and ZnI2 in THF, which promotes the reaction of PhSO2CHBr2 with carbonyl compounds to afford conjugated sulfones.1 1

Baba, Y., Toshimitsu, A., Matsubara, S. CL 36, 864 (2007).

Titanium(IV) chloride. New preparation.1 From titanium oxide, HCl and a carbon source, microwave heating produces TiCl4. This carbohydrochlorination method also works for generating SiCl4 and BCl3.

b-Methoxyamino esters.2 A Mannich-type reaction between RCH ¼ NOMe and esters is catalyzed by a combination of TiCl4 and s-BuNH2. Rearrangement.3 Protic and Lewis acids usually facilitate cleavage of strained cyclic compounds possessing oxygen functionalities and/or unsaturation. 7-Methylenebicyclo[3.2.0]heptan-2-ones deliver bridged ring products that appear to suggest a synthetic potential to elaboration of the AB-ring segment of taxol.

MO

O

O

TiCl4 CH2Cl2 25o

H

Cyclization.4 A pleasing and obviously valuable transformation is the bicyclization involving the reaction of a bis(allylsilane) with oxalyl chloride.

438

Titanium(IV) chloride–magnesium

Me3Si

TiCl4

O

H

(COCl)2

OH

CH2Cl2, MeNO2 –60° ~ –90°

Me3Si

64%

2-Oxalobiaryls give phenanthrenequinones after treatment of their imidazolide derivatives with TiCl4.5

R

R COOH O

Im2CO;

O

TiCl4 CH2Cl2

O

MeO

MeO

Isoxazolidines.6 N-Nosyloxaziridines engage in 1,3-dipolar cycloaddition in the presence of TiCl4. The process is highly stereoselective.

Ar

+

O N

Ns

Ph

Ns O N

TiCl4 PhMe 23°

Ar

Ph

(cis : trans >10 : 1)

1

Nordschild, S., Auner, N. CEJ 14, 3694 (2008). Funatomi, T., Nakazawa, S., Matsumoto, K., Nagase, R., Tanabe, Y. CC 771 (2008). 3 Shimada, Y., Nakamura, M., Suzuka, T., Matsui, J., Tatsumi, R., Tsutsumi, K., Morimoto, T., Kurosawa, H., Kakiuchi, K. TL 44, 1401 (2003). 4 Auof, C., El Abed, D., Giorgi, M., Santelli, M. TL 49, 3862 (2008). 5 Yoshikawa, N., Doyle, A., Tan, L., Murry, J.A., Akao, A., Kawasaki, M., Sato, K. OL 9, 4103 (2007). 6 Partridge, K.M., Anzovino, M.E., Yoon, T.P. JACS 130, 2920 (2008). 2

Titanium(IV) chloride –magnesium. Ketones from amides. A methylenating agent is generated from CH2Cl2 in the presence of TiCl4 and magnesium metal and it reacts with amides to give methyl ketones, after hydrolytic workup.1 Since enamine formation is implicated it can be exploited for the synthesis of d-keto esters and congeners.2

Titanium(IV) chloride–zinc

439

O R

N O

TiCl4–Mg

O +

Et3N, CH2Cl2

COOMe

R

COOMe 1

Lin, K.-W., Tsai, C.-H., Hsieh, I.-L., Yan, T.-H. OL 10, 1927 (2008). Lin, K.-W., Chen, C.-Y., Chen, W.-F., Yan, T.-H. JOC 73, 4759 (2008).

2

Titanium(IV) chloride –Mischmetal. De-N-tosylation.1 Tosylamines are cleaved by heating with the title reagent combination in THF. 1

Vellema¨e, E., Lebedev, O., Ma¨eorg, U. TL 49, 1373 (2008).

Titanium(IV) chloride –zinc. Coupling 1 rearrangement.1 Pinacol coupling of cyclobutanone with a diaryl ketone, when mediated by TiCl4 –Zn, is followed by rapid ring expansion (yields of the products are increased by adding catechol to the reaction media). With TiCl4 –Mg(HgCl2) the normal McMurry coupling prevails. O

Ar +

O

catechol THF

Ar

O

Ar

TiCl4 –Zn

Ar

Cyclization and RCM.2 Low-valent titanium species generated from TiCl4 –Zn– PbCl2 and with the presence of MeCHBr2 forms Ti-alkylidenes with terminal alkenes. Intramolecular reaction involving such entities and an ester carbonyl group leads to cyclic enol ethers. Ring-closing metathesis from a,v-dienes is also effected by such reagents. O O

R' R'

TiCl4–Zn

O

PbCl2, MeCHBr2

R

TMEDA / THF

O R

1

R

O

TiCl4–Zn PbCl2, MeCHBr2 TMEDA / THF

R

Seo, J.W., Kim, H.J., Lee, B.S., Katzenellenbogen, J.A., Chi, D.Y. JOC 73, 715 (2008). Iyer, K., Rainier, J.D. JACS 129, 12604 (2007).

2

440

Titanium tetraisopropoxide–magnesium

Titanium tetraisopropoxide– magnesium. Ether cleavage. Propargyl ethers and allyl ethers suffer cleavage on exposure to (i-PrO)4Ti–Mg and Me3SiCl. With addition of EtOAc propargyl ethers are cleaved more rapidly than allyl ethers.1

O

OH (i-PrO)4Ti–Mg

(i-PrO)4Ti–Mg Me3SiCl

Me3SiCl EtOAc (2 eq.) THF

O

OBn BnBr, base;

O

OH 100%

91% 1

Ohkubo, M., Mochizuki, S., Sano, T., Kawaguchi, Y., Okamoto, S. OL 9, 773 (2007).

Titanium tetrakis(diethylamide). Hydroamination.1 On exchanging two of the Et2N groups of the title reagent to N-(2,6-diisopropylphenyl)benzamido residues, a precatalyst for anti-Markovnikov hydroamination of 1-alkynes to form aldimines is readily obtained. 1

Zhang, Z., Leitch, D.C., Lu, M., Patrick, B.O., Schafer, L.L. CEJ 13, 2012 (2007).

Titanocene bis(triethyl phosphite). Polyene synthesis. In the presence of titanocene bis(triethyl phosphite), activated alkynes react with (Z )-alkenyl sulfones to give conjugated dienes in a highly regioselective and stereoselective fashion.1 Mixed unsaturated sulfones react in an analogous manner, and when the titanated coupling adducts are quenched with carbonyl compounds it results in 1,2,4-trienes.2

R' R

THF 0o

X

SO2Me

R'

Cp2Ti[P(OEt)3]2

+

X

R

X = COOLi, PO(OEt)2

R' R

+ SO2Me

R'

Cp2Ti[P(OEt)3]2 O

SO2Ph

R"

R

C

R"

R"

R"

Titanocene dichloride –zinc

441

Homopropargylic alcohols. A three-component condensation unites an alkynyl sulfone, a carbonyl compound, and a dithioacetal, resulting in a homopropargylic alcohol.3 R

R'CH(SPh)2

R

+

R'

Cp2Ti[P(OEt)3]2

O SO2Me

R"

R" R"

R"

OH

1

Ogata, A., Nemoto, M., Takano, Y., Tsubouchi, A., Takeda, T. TL 49, 3071 (2008). Ogata, A., Nemoto, M., Kobayashi, K., Tsubouchi, A., Takeda, T. CEJ 13, 1320 (2007). 3 Takeda, T., Ando, M., Sugita, T., Tsubouchi, A. OL 9, 2875 (2007). 2

Titanocene dichloride –manganese. Aldols from a-haloketones.1 The Reformatsky-type reaction is readily effected at room temperature with the assistance of titanocene chloride, which is generated from Cp2TiCl2 and manganese in THF. Aromatic aldehydes are not suitable for the reaction as they tend to undergo pinacol coupling under the reaction conditions. 1

Estevez, R.E., Paradas, M., Millan, A., Jimenez, T., Robles, R., Cuerva, J.M., Oltra, J.E. JOC 73, 1616 (2008).

Titanocene dichloride –zinc. Allylic substitution.1 Alkyltitanocenes are nucleophilic toward allylic acetates such as those derived from Baylis–Hillman adducts. Accordingly, it is applicable to the synthesis of a-alkyl-a,b-unsaturated esters.

R

COOMe

Br +

R

Cp2TiCl2–Zn

R'

THF ; H3O+

OAc

COOMe R'

Reductive cyclization.2 Epoxides substituted with a carbon chain terminated (at a proper length) in an allenyl group are converted into cyclic products containing vicinal hydroxymethyl and vinyl substituents. C R

O X

R

HO Cp2TiCl2 –Zn

X = O, NTs 1

Mandal, S.K., Paira, M., Roy, S.C. JOC 73, 3823 (2008). Xu, L., Huang, X. TL 49, 500 (2008).

2

R

THF;

X

R

442

p-Toluenesulfonic anhydride

p-Toluenesulfonic anhydride. 2-Aminopyridine.1 Tosic anhydride is used in activating pyridine-N-oxide and homologues for attack by t-butylamine. The resulting 2-t-butylaminopyridine is dealkylated by CF3COOH. 1

Yin, J., Xiang, B., Huffman, M.A., Raab, C.E., Davies, I.W. JOC 72, 4554 (2007).

p-Toluenesulfonyl chloride. Tosylation.1 A method for selective tosylation of primary alcohols (in the presence of secondary alcohols) consists of grinding with TsCl at room temperature. If KOH is present secondary alcohols are also tosylated. Isothiocyanates. Primary amines are converted into isothiocyanates by combining with carbon disulﬁde and decomposing the dithiocarbamic acid salts with TsCl.2 1

Kazemi, F., Massah, A.R., Javaherian, M. T 63, 5083 (2007). Wong, R., Dolman, S.J. JOC 72, 3969 (2007).

2

p-Toluenesulfonyl ﬂuoride. Tosylates.1 A direct transformation of silyl ethers into tosyl esters is accomplished by the treatment with TsF and DBU in MeCN at room temperature. 1

Gembus, V., Marsais, F., Levacher, V. SL 1463 (2008).

1-( p-Toluenesulfonyl)imidazole. Esteriﬁcation.1 Carboxylic acids in the sodium salt form are esteriﬁed by various alcohols on heating with the title reagent and Bu4NI, Et3N in DMF. Alkyl azides. In situ activation of alcohols (to ROTs) for conversion into azides is by heating with the title reagent, reaction with NaN3 that is present (also Et3N and Bu4NBr) completes the transformation.2 1

Rad, M.N.S., Behrouz, S., Faghihi, M.A., Khalaﬁ-Nezhad, A. TL 49, 1115 (2008). Rad, M.N.S., Behrouz, S., Khalaﬁ-Nezhad, A. TL 48, 3445 (2007).

2

p-Toluenesulfonyl isocyanate. N-Tosyl amides. Carboxylic acids react with TsNvCvO to afford RCONHTs.1 These amides can be transformed into thioesters in two step: N-methylation (MeI, K2CO3, DMF) and treatment with RSH.2 1

Manabe, S., Sugioka, T., Ito, Y. TL 48, 787 (2007). Manabe, S., Sugioka, T., Ito, Y. TL 48, 849 (2007).

2

O-( p-Toluenesulfonyl)-N-methylhydroxylamine. a-Tosyoxylation of ketones.1 A tosyloxy group is readily introduced at an a-position of an enolizable ketone by reaction with TsONHMe in MeOH. 1

John, O.R.S., Killeen, N.M., Knowles, D.A., Yau, S.C., Bagley, M.C., Tomkinson, N.C.O. OL 9, 4009 (2007).

2,8,9-Trialkyl-1-phospha-2,5,8,9-tetraazabicyclo[3.3.3]undecanes

443

Trialkylboranes. Carbamoylation. Tertiary amines give N-phenyl a-aminocarboxamides on reaction with PhNCO in the presence of Et3B and air.1 R'

R'

Et3B

+

R2N

O=C=NPh

air

NHPh

R2N O

Reduction.

Alkyl iodides are reduced in water by exposure to air and Bu3B.2

N-Heteroarylation.3 In the Pd-catalyzed substitution of heteroaryl halides (e.g., bromopyridines) with amides and sulfonamides the yields are greatly increased in the presence of Et3B. Coordination of the Lewis acid by the nuclear nitrogen atom accelerates the reductive elimination step. Hydrostannylation.4 The free radical mode of addition involving Bu2Sn(H)I and 2-allyloxymethyl-1-methylenecyclopropanes leads to tetrahydrofurans substituted with an a-stannylvinyl group at C-3. Cleavage of the three-membered ring occurs at the proximal bond. Bu I Sn Bu Ph

Ph

Et3B

THF

+ Bu2Sn(H)I

O

O 1

Yoshimitsu, T., Matsuda, K., Nagaoka, H., Tsukamoto, K., Tanaka, T. OL 9, 5115 (2007). Medeiros, M.R., Schacherer, L.N., Spiegel, D.A., Wood, J.L. OL 9, 4427 (2007). 3 Shen, Q., Hartwig, J.F. JACS 129, 7734 (2007). 4 Hayashi, N., Hirokawa, Y., Shibata, I., Yasuda, M., Baba, A. JACS 130, 2912 (2008). 2

2,8,9-Trialkyl-1-phospha-2,5,8,9-tetraazabicyclo[3.3.3]undecanes. Diaryl ethers.1 With one of the congeners (1, R ¼ i-Bu) present a mixture of ArOTBS and Ar0 F react under microwave irradiation to give ArOAr0 . R

R N P

N

N R

Ar-OTBS + Ar'F (1)

w

N

(1 ) 1

Raders, S.M., Verkade, J.G. TL 49, 3507 (2008).

Ar-O-Ar'

444

Trialkylphosphines

Trialkylphosphines. Reduction.1 Reduction of ArCOCF3 to ArCH(OH)CF3 is observed on mixing with equimolar of Bu3P in toluene at room temperature. Reaction of oximes. Ketoximes are transformed into N-acetyl enamines by heating with Ac2O in toluene in the presence of a trialkylphosphine.2 Formation of N-phenylthio ketimines from either oximes or nitroalkanes is also catalyzed by Me3P, with the PhS group provided by N-phenylthiophthalimide.3 Cycloaddition. Trapping of CO2 (from supercritical carbon dioxide) into propargylic alcohols to form 4-alkylidene-1,3-dioxolan-2-ones is assisted by Bu3P.4 The high afﬁnity of allenoic esters to phosphines enables catalytic activation of the g-carbon to engage in nucleophilic addition. Thus with Me3P the condensation of methyl 2,3-butadienoate with ArCHO to give 6-aryl-5,6-dihydro-2-pyrones, catalytic amounts of the phosphine are required in the presence of ROH or ROLi.5 (Additional advantage is that such additives/reactants favor the formation of the phosphonium dienolates in the s-cis-form.) C Ar CHO

OMe

COOMe Me3P, MeOLi

+

CH2Cl2

Ar

O

O

Intramolecular trapping of an adduct derived from R3P and allenoic ester by a conjugated nitroalkene can lead to different results in accordance with the phosphine used.6 O2N R3P/THF

NO2

O

C O

H

(R=Bu, Ph)

O O N

O

O

(4-FC6H4)3P PhH

O 1

O

Shi, M., Liu, X.-G., Guo, Y.-W., Zhang, W. T 63, 12731 (2007). Zhao, H., Vandenbossche, C.P., Koenig, S.G., Singh, S.P., Bakale, R.P. OL 10, 505 (2008). 3 Bures, J., Isart, C., Vilarrasa, J. OL 9, 4635 (2007). 4 Kayaki, Y., Yamamoto, M., Ikariya, T. JOC 72, 647 (2007). 5 Creech, G.S., Kwon, O. OL 10, 429 (2008). 6 Henry, C.E., Kwon, O. OL 9, 3069 (2007). 2

Tributyltin hydride –2,20 -azobis(isobutyronitrile)

445

Tributyltin hydride. Hydrostannylation. Regioselective conversion of 1-alkynes to 2-tributylstannyl-1alkenes is accomplished with Bu3SnH in the presence of (t-BuNC)3Mo(CO)3.1,2 By changing the catalyst to ( p-O2NC6H4NC)3W(CO)3 propargyl acetate furnishes a distannylated product.2

Bu3SnH +

(t-BuNC)3Mo(CO)3

O NBoc

THF 60o

SnBu3

O NBoc

(regiosel. 9 : 1)

(t-BuNC)3Mo(CO)3

OR

THF

Bu3Sn

OR

60o

Bu3SnH +

(ArNC)3W(CO)3

Bu3Sn

OR

THF 60o

Bu3Sn

1

Lin, H., Kazmaier, U. EJOC 2839 (2007). Wesquet, A.O., Kazmaier, U. ACIE 47, 3050 (2008).

2

Tributyltin hydride –2,20 -azobis(isobutyronitrile). Cyclizations. N-Diphenylmethylene derivatives of o-bromoarylethylamines form aryl radicals that add to the nitrogen atom to give indolines.1

EtOOC

COOEt R O

Br

N

EtOOC R O Ph

Bu3SnH–AIBN PhH

Ph

COOEt O

N O CHPh2

The tricyclic core of stemonamide is formed (55% yield) in one step via sequential Michael reactions initiated by an alkyl radical.2 The selectivity of the process is due to the much greater tendency, at the start, to form a seven-membered ring than a eightmembered ring. [1,10 -bis(cyclohexanecarbonitrile) instead of AIBN is used as radical initiator in this case.]

Tributyltin hydride –2,20 -azobis(isobutyronitrile)

446

O O O

O

N

CN CN N N

Br

O O

MeO

Bu3SnH

O

N

O

N

PhMe

stemonamide

A tandem double cyclization is initiated on forming an aryl radical from an N-acrylyl-Ncyano-o-iodobenzylamine. Addition onto the cyano group is followed by a 1,4-addition of the iminyl radical.3 O O I

Bu3SnH–AIBN

N CN

N

PhH

N 66%

Fragmentation. Hydrogen abstraction is the predominant event for the aryl radicals generated from o-iodoarylanilides. When the acyl residue contains an a-azido substituent, the transposed C-radicals rapidly lose N2 and then fragment.4 Me N

Me N

O Bu3SnH

R

O

CHO

R

AIBN

I N3

N

H N

+ RCN

Carbonylation. Dichlorocarbene adducts of alkenes are transformed into cyclopropanecarbaldehydes with Bu3SnH –AIBN under CO. Radical carbonylation and hydrodechlorination are involved.5

H

H Bu3SnH

Cl

+ CO

CHO

AIBN

Cl

H

H

55% R

R X

R

X

X = H, allyl

R'SnBu3, CO

X

AIBN 80o

R

COR

Triethyl phosphite

447

1

Viswanathan, R., Smith, C.R., Prabhakaran, E.N., Johnston, J.N. JOC 73, 3040 (2008). Taniguchi, T., Tanabe, G., Muraoka, O., Ishibashi, H. OL 10, 197 (2008). 3 Servais, A., Azzouz, M., Lopes, D., Courillon, C., Malacria, M. ACIE 46, 576 (2007). 4 Bencivenni, G., Lanza, T., Leardini, R., Minozzi, M., Nanni, D., Spagnolo, P., Zanardi, G. JOC 73, 4721 (2008). 5 Nishii, Y., Nagano, T., Gotoh, H., Nagase, R., Motoyoshiya, J., Aoyama, H., Tanabe, Y. OL 9, 563 (2007). 2

Tricarbonyl(cyclopentadienyl)hydridochromium. Radical cyclization.1 The CpCr(CO)3H complex initiates H addition to CvC to form a carbon radical. A 1,6-diene is induced cyclize. The transition metal hydride is used as a catalyst while hydrogen is consumed.

MeOOC

Ph

MeOOC Ph

CpCr(CO)3H H2

R R

Ph Ph

R R

1

Smith, D.M., Pulling, M.E., Norton, J.R. JACS 129, 770 (2007).

Trichloroacetonitrile. Dihydrooxazines.1 Certain 1,3-diols form the heterocycles on reaction with Cl3CCN in the presence of DBU, by way of an intramolecular displacement. 1

Rondot, C., Retailleau, P., Zhu, J. OL 9, 247 (2007).

Trichlorosilane. Enolsilylation.1 a-Bromo ketones and esters are transformed into trichlorosilyl enol ethers by HSiCl3 and Et3N (catalytic Ph3PO), which condense with ArCHO. The overall process is superior to the Wittig reaction. 1

Smith, J.M., Greaney, M.F. TL 48, 8687 (2007).

Triethyl phosphite. Heterocyclization.1 Certain o-nitroarylalkenes cyclize on heating with (EtO)3P by involving the nitro group at a reduced state with a double bond of the side chain at an o-position. Tetrahydroquinolines, tetrahydroquinoxalines, and dihydrobenzoxazines are obtained.

448

Triethylsilyl chloride

NO2

H N

(EtO)3P

R

w

R X

X

R = H, Me

1

Merisor, E., Conrad, J., Klaiber, I., Mika, S., Beifuss, U. ACIE 46, 3353 (2007).

Triethylsilyl chloride. O-Silylation.1 This silyl chloride can be used to selectively derivatize an allylic hydroxyl group in the presence of a homoallylic OH.

OH OH

OH

Et3Si

R'

(EtO)3SiCl

O

imidazole, DMAP DMF, CH 2Cl2

R

R'

R

–78°

1

Hicks, J.D., Huh, C.W., Legg, A.D., Roush, W.R. OL 9, 5621 (2007).

Triﬂuoroacetic acid, TFA. Dehydration.1 Dissolution of 2-(a-hydroxyalkyl)cyclopropanols in CF3COOH causes ionization and ring opening, b,g-unsaturated carbonyl compounds are formed. Since the substrates are usually synthesized from conjugated lower homologues, the overall result is a methylene group insertion between the carbonyl group and the a-carbon atom.

OH OH R

O

CF3COOH

R'

R

R'

1

Nomura, K., Matsubara, S. SL 1412 (2008).

Triﬂuoroacetic anhydride, TFAA. Triﬂuoromethyl ketones.1 A simple preparation of RCOCF3 involves heating carboxylic acids with pyridine and TFAA in toluene at 60–1008, then hydrolysis with water at 458. 1

Reeves, J.T., Gallou, F., Song, J.J., Tan, Z., Lee, H., Yee, N.K., Senanayake, C.H. TL 48, 189 (2007).

Triﬂuoromethanesulfonic acid (triﬂic acid)

449

1,1,1-Triﬂuoroacetone. Oppenauer oxidation.1 Oxidation of secondary alcohols is accomplished with Et2AlOEt and CF3COMe at room temperature. 1

Mello, R., Martinez-Terrer, J., Asensio, G., Gonzalez-Nunez, M.E. JOC 72, 9376 (2007).

2,2,2-Triﬂuoroethyl isocyanate. Hofmann–Lo¨fﬂer –Freytag reaction.1 Derivatization by the title reagent (prepared from 2,2,2-triﬂuoroethylamine and phosgene) transforms an alcohol into a N-(2,2,2triﬂuoroethyl)carbamate, which on subjecting to a Hofmann –Lo¨fﬂer –Freytag reaction delivers the cyclic carbonate of a 1,3-diol. O=C=N OH R

O

CF3

O

CF3

+

O Py

R'

N H

R

O R'

R

O R'

1

Chen, K., Richter, J.M., Baran, P.S. JACS 130, 7247 (2008).

Triﬂuoromethanesulfonic acid (triﬂic acid). Cyclization. Cyanoacetic esters undergo O,N-diprotonation in TfOH. If the ester bears a benzyl or phenylethyl group at the a-position, the derived dication would undergo an intramolecular Friedel –Crafts reaction.1 NH2 CF3SO3H

CN n

COOMe

COOMe

n

n = 1, 2

Smooth aza-Nazarov cyclization to form dihydroisoindolones is observed with TfOH where CF3COOH is totally ineffectual. Formation of dicationic superelectrophilic species is apparently important for overcoming the energy barrier of the cyclization in such cases.2 O

O CF3SO3H

N

N Cl

Ph

Ph 53%

450

Triﬂuoromethanesulfonic anhydride (triﬂic anhydride)

A highly unusual yet simple ring closure of 2-arylnitroethanes to 4H-1,2-benzoxazines is accomplished by heating with TfOH.3

COOMe

COOMe

CF3SO3H

NO2

CHCl3

O

N

Friedel– Crafts alkylation. Alkenes (styrenes and trisubstituted alkenes) alkylate indoles at the b-position in CH2Cl2 containing 5 mol% of TfOH (or an Au(III) species).4 Benzyl triﬂuoromethyl carbinols are obtained from reaction of arenes with triﬂuoromethyl epoxides. The direction of epoxide ring opening is determined by the electronwithdrawing triﬂuoromethyl group.5 1

Nakamura, S., Sugimoto, H., Ohwada, T. JOC 73, 4219 (2008). Klumpp, D.A., Zhang, Y., Oconnor, M.J., Esteves, P.M., de Almeida, L.S. OL 9, 3085 (2007). 3 Nakamura, S., Sugimoto, H., Ohwada, T. JACS 129, 1724 (2007). 4 Rozenman, M.M., Kanan, M.W., Liu, D.R. JACS 129, 14933 (2007). 5 Prakash, G.K.S., Linares-Palomino, P.J., Glinton, K., Chacko, S., Rasul, G., Mathew, T., Olah, G.A. SL 1158 (2007). 2

Triﬂuoromethanesulfonic anhydride (triﬂic anhydride). Conjugate addition. Allyl transfer from allyltributylstannane to enals, enones, and enoates in the presence of Tf2O and 2,6-di-t-butylpyridine affords enol triﬂates.1 Reduction. Carboxamides are reduced to amines with Hantzsch ester, upon conversion (in situ) into N,O-ketene triﬂates with Tf2O.2 Cycloaddition. The combination of enamides with alkynes (or enol ethers)3 and with nitriles4 gives substituted pyridines and pyrimidines, respectively, as promoted by Tf2O.

R5 R4

HN

+ R1

O

R5

R3

R2

CH2Cl2 N

Cl

R4

N

(CF3SO2)O

R1

R3 2

R

Pummerer rearrangement of 4-benzenesulﬁnyl-1-naphthols generates naphthoquinone phenylsulfonium ions. These react with enol ethers to afford annulated furanyl ethers.5 Another Pummerer rearrangement on aryl substituted ketene dithioacetal monoxides provides 2-methylthiobenzothiophenes.6

Triﬂuoromethanesulfonic anhydride (triﬂic anhydride)

451

O OH Ph

O O

+ S O

(CF3SO2)O

OCOOMe

O

S

PhS

collidine MeCN –40°

OCOOMe

S

(CF3SO2)O

SMe

SMe

K2CO3, PhMe; HOCH2CH2NH2

R

R

R = Ar, CF 3

In an approach to stemofoline the elaboration of the tricyclic system involves generation of a 1,3-dipolar species from a vinylogous N-trimethylsilylmethyl amide. The design also provides a proper dipolarophile.7 Me3Si

EtS

SEt

O

N (CF3SO2)O

O

H

H O O

TfO H

Bu4 N(Ph3SiF2)

O

H O

CHCl3

O

71%

Fragmentative elimination. N-Oxides of the tetracyclic segment common to Aspidosperma and Strychnos alkaloids are converted into the tricyclic lactam isomers after treatment with Tf2O and quenched with water.8 Cyclic nitrilium ions intervene in this transformation. O N

H N (CF3SO2)O;

N H Bn

H2O

N Bn 82%

1

Beaulieu, E.D., Voss, L., Trauner, D. OL 10, 869 (2008). Barbe, G., Charette, A.B. JACS 130, 18 (2008).

2

O

452

Triﬂuoromethanesulfonic imide (triﬂic imide)

3

Movassaghi, M., Hill, M.D., Ahmad, O.K. JACS 129, 10096 (2007). Movassaghi, M., Hill, M.D. JACS 128, 14254 (2006). 5 Akai, S., Kakiguchi, K., Nakamura, Y., Kuriwaki, I., Dohi, T., Harada, S., Kubo, O., Morita, N. ACIE 46, 7458 (2007). 6 Yoshida, S., Yorimitsu, H., Oshima, K. OL 9, 5573 (2007). 7 Carra, R.J., Epperson, M.T., Gin, D.Y. T 64, 3629 (2008). 8 Murphy, J.A., Mahesh, M., McPheators, G., Anand, R.V., McGuire, T.M., Carling, R., Kennedy, A.R. OL 9, 3233 (2007). 4

Triﬂuoromethanesulfonic imide (triﬂic imide). Aldol reaction.1 Catalyzed by Tf2NH, the Mukaiyama aldol reaction of tris(trimethylsilyl) ethers of enolized ketones affords products that react with Grignard reagents diastereoselectively. Diels–Alder reaction.2 The condensation of N-arylaldimines and allylsilanes is catalyzed by Tf2NH. Some of the products also undergo aromatization to give 2-aryl-4silylmethylquinolines. 1

Boxer, M.B., Akakura, M., Yamamoto, H. JACS 130, 1580 (2008). Shindoh, N., Tokuyama, H., Takasu, K. TL 48, 4749 (2007).

2

Triﬂuoromethyltrimethylsilane. Triﬂuoromethylation.1 Reagent 1, useful for triﬂuoromethylation of 1,3-dicarbonyl compounds and thiols, is obtained by reaction of the corresponding chloroiodine compound with Me3SiCF3. O I CF3

(1) 1

Kieltsch, I., Eisenberger, P., Togni, A. ACIE 46, 754 (2007).

Trimethylsilylacetonitrile. Cyanomethylation. Carbonyl compounds and imines are subject to cyanomethylation by Me3SiCH2CN with tris(2,4,6-trimethoxyphenyl)phosphine as catalyst.1 1

Matsukawa, S., Kitazaki, E. TL 49, 2982 (2008).

Trimethylsilyl azide. Organic azides. A method for the preparation of aryl azides from arylamines consists of reaction with t-BuONO and Me3SiN3 in MeCN.1

Trimethylsilyl chloride

453

Arenediazonium tetraﬂuoroborates can be converted into aryl azides under mild conditions, by reaction with Me3SiN3 in an ionic liquid at room temperature.2 Analogously, aryl bromides and iodides are formed with Me3SiX (X ¼ Br, I). Tetrazoles.3 Nitriles undergo Cu-catalyzed cycloaddition with Me3SiN3 and adducts are desilylated in situ to furnish ﬁve-substituted tetrazoles.

R

Cu2O

R-CN +

Me3Si N3

MeOH, DMF

H N

N N N

80o

1

Barral, K., Moorhouse, A.D., Moses, J.E. OL 9, 1809 (2007). Hubbard, A., Okazaki, T., Laali, K.K. JOC 73, 316 (2008). 3 Jin, T., Kitahara, F., Kamijo, S., Yamamoto, Y. TL 49, 2824 (2008). 2

Trimethylsilyl chloride. Cyanosilylation. Me3SiCl mediates formation of a-cyanohydrin trimethylsilyl ether using NaCN in DMSO. This combination is more economical than Me3SiCN.1 (Z)-2,4-Diiodo-2-butenol.2 An apparently valuable allylic alcohol is obtained in one step from 2-butyne-1,4-diol by reaction with Me3SiCl– NaI. HO

Me3SiCl–NaI

I

I

OH

OH

Oxidation.3 In the presence of Me3SiCl aromatic sulfur compounds are oxidized by KNO3, which includes the transformations of ArSH to ArSO2Cl and Ar2S(O)n to Ar2S(O)nþ1 where [n ¼ 0, 1]. Condensation.4 Warming heteroarylmethylamines and 3-formylchromone with Me3SiCl in DMF at 608 gives 2-heteroaryl-4-(o-benzoyl)pyrroles in moderate to excellent yields. O

O CHO

R +

O

1

HN

Me3SiCl

R

DMF

R'

OH

N R'

Cabirol, F.L., Lim, A.E.C., Hanefeld, U., Sheldon, R.A., Lyapkalo, I.M. JOC 73, 2446 (2008). Taber, D.F., Sikkander, M.I., Berry, J.F., Frankowski, K.J. JOC 73, 1605 (2008). 3 Prakash, G.K.S., Mathew, T., Panja, C., Olah, G.A. JOC 72, 5847 (2007). 4 Plaskon, A.S., Ryabukhin, S.V., Volochnyuk, D.M., Shivanyuk, A.N., Tolmachev, A.A. T 64, 5933 (2008). 2

454

Trimethylsilyl cyanide

Trimethylsilyl cyanide. Cyanation reactions. New catalysts for converting carbonyl compounds to O-trimethylsilyl cyanohydrins by Me3SiCN include Cp2FePF61 and NbF5.2 Derivatization of ketones can use the titanium complex of 1 3 or (Ph3PBn)Cl.4

O

CHPh2 N H N

OH

H

CHPh2 N O N

(1) Strecker reaction can be performed at room temperature without solvent. Products are directly obtained (no workup handling).5 Still, reports abound with various catalysts (e.g., sulfamic acid6). By ligand exchange to deliver a cyano group from Me3SiCN to PhI(OCOCF3)2 in the presence of BF3 . OEt2, cyanating agent(s) for heteroaromatic compounds, PhI(CN)X, where X ¼ OCOCF3 or CN, are formed.7 Double trapping. Normally, adducts obtained from trapping of ionized acetonides with Me3SiCN have little synthetic value. However, the observation that further reaction of the cyano group with an internal azide to form a tetrazole unit8 is worth attention.

O N3

BF3 · OEt2 MeCN

1

N

Me 3SiCN

O

N

N N

O OH

Khan, N.H., Agrawal, S., Kureshy, R.I., Abdi, S.H.R., Singh, S., Suresh, E., Jasra, R.V. TL 49, 640 (2008). 2 Kim, S.S., Rajagopal, G. S 215 (2007). 3 Shen, K., Liu, X., Li, Q., Feng, X. T 64, 147 (2008). 4 Wang, X., Tian, S.-K. TL 48, 6010 (2007). 5 Baeza, A., Najera, C., Sansano, J.M. S 1230 (2007). 6 Li, Z., Sun, Y., Ren, X., Wei, P., Shi, Y., Ouyang, P. SL 803 (2007). 7 Dohi, T., Morimoto, K., Takenaga, N., Goto, A., Maruyama, A., Kiyono, Y., Tohma, H., Kita, Y. JOC 72, 109 (2007). 8 Hanessian, S., Simard, D., Deschenes-Simard, B., Chenel, C., Haak, E. OL 10, 1381 (2008).

Trimethylsilyl triﬂuoromethanesulfonate

455

Trimethylsilyldiazomethane. Methylenation. Methylenation of carbonyl compounds using Me3SiCHN2 in some situations is followed by cyclization of the products, for example, to give indoles from o-aminobenzaldehyde and in a synthesis of the indolizines.1

O N

Me3SiCHN2

R'

R

R CHO NH2

R'

N

MeOH

Me3SiCHN2 Cs2CO3, MeOH

N H 53%

The methylenation in the presence of an imidazolylidene-CuCl complex and Ph3P is also reported.2 1,2,3-Triazoles. An adduct from Cp2 Sm and Me3SiCHN2 reacts with RCN to furnish substituted 1,2,3-triazoles.3 But the usefulness of the adduct for synthesis is unknown. 1-Silyl-3-borylallenes. Alkynylboranes react with Me3SiCHN2 by way of 1,2insertion and 1,3-borotropic rearrangement.4 The products are a-silylpropargylating agents.

R Me3Si

R C

B SiMe3

Me3SiCHN2

B SiMe3

hexane 25°

100% 1

Zhu, L., Vimolratana, M., Brown, S.P., Medina, J.C. TL 49, 1768 (2008). Lebel, H., Davi, M., Diez-Gonzalez, S., Nolan, S.P. JOC 72, 144 (2007). 3 Evans, W.J., Montalvo, E., Champagne, T.M., Ziller, J.W., DiPasquale, A.G., Rheingold, A.L. JACS 130, 16 (2008). 4 Canales, E., Gonzalez, A.Z., Soderquist, J.A. ACIE 46, 397 (2007). 2

Trimethylsilyl triﬂuoromethanesulfonate. Deprotection. The ring system of an N,O-acetonide breaks apart on treatment with Me3SiOTf.1

456

Triphenylphosphine

Cyclocondensation. Two different processes depend on the catalysis of Me3SiOTf in the construction of a cyclohexanopyrrole intermediate for a synthesis of goniomitine.2 It assists the cleavage of a push-pull cyclopropane ring and the condensation with a nitrile unit.

E OMe

E

+

Me3SiOTf

O

NC

O

HN

EtNO2

E = COOEt

NBn

–30°

NBn

74%

The condensation of benzyl cyclopropyl ketones with ethyl 2,3-butadienoate is interesting. The furocoumarin system is elaborated.3 O O Ar

Ar EtO

Me3SiOTf

+ C

O

Ar OSiMe3

Cl

COOEt

O

+

Cl

C

60o

O

COOEt

1

Poon, K.W.C., Lovell, K.M., Dresner, K.N., Datta, A. JOC 73, 752 (2008). Morales, C.L., Pagenkopf, B.L. OL 10, 157 (2008). 3 Shi, M., Tang, X.-Y., Yang, Y.-H. OL 9, 4017 (2007). 2

Triphenylphosphine. Substitution. In converting ArOH to t-BuOCOOAr by Boc2O in the neat,1 and the group exchange in HC(OEt)3 to form N,O,O-ortho esters with lactams,2 Ph3P serves as a catalyst. In the latter reaction a cocatalyst Me3SiCl is present. Ring strain makes trimethylsilylcyclopropenes susceptible to attack by Ar3P such that further reaction with aldehyde is realized. A Brook-type rearrangement drives the reaction to completion by expulsion of the Ar3P from the adducts. In practice, tris(2,4,6-trimethoxyphenyl)phosphine is used instead of Ph3P (much better yields).3 ROOC + PhCHO ROOC

Ar3P

ROOC OSiMe3

ROOC

SiMe3 Ar = 2,4,6-(MeO)3C6H2

Ph 79%

Triphenylphosphine

457

Cyclization and cycloaddition. Through creation of ylides and related zwitterionic species from activated allenes, Michael reaction is readily initiated. Options for further transformations leading to highly functionalized cyclic systems are as many as designed: reﬂexive Michael reactions to give bicyclo[n.3.0]cycloalkenes,4 a regiochemically switchable cycloaddition to alkylidenemalononitriles [using tris(4-ﬂuorophenyl)phosphine as catalyst],5 and spiroannulation of a-methylenecycloalkanones.6 Br

COOR

H Ph3P

COOR

Cs2CO3

COOR

PhMe 90o

H

COOR

73% NC

R

(4-FC6H4)3P

R

PhH

NC COOEt

NC CN + C

NC COOEt

(4-FC6H4)3P

R

NC

HMPA

COOEt O

O

+

O

C

O

Ph3P

vic-Azido alcohols are converted into aziridines upon treatment with Ph3P, via a Staudinger reaction, N -. O shift of the phosphino group, and intramolecular Mitsunobu reaction. In one example, the aziridine group acts as a nucleophile to participate in an intramolecular Michael reaction.7

ROOC OH

NHCbz

Cbz HN Ph3P MeCN

N3

COOR H N

66%

458

Triphenylphosphine–dialkyl azodicarboxylate

Using Ph3P to induce Staudinger reaction of a-azidocinnamic esters as well as Wolff rearrangement of a-diazo ketones, two types of mutually reactive molecules are formed. The natural course for aza-Wittig reaction is pursued to produce cyclization-prone ketene imines.8

COOEt

COOEt

Ph3P

N

N3 N2

+

R'

R'

R O

PPh3

R

C

COOEt O

N COOEt

C

R' R

N R

R'

Heating aziridines and diazodicarboxylic esters with Ph3P in toluene gives 5-aminopyrazolines.9 Henry reaction. The 2,4,6-trimethoxy analogue [i.e., tris(2,4,6-trimethoxyphenyl)phosphine] is found to be a nonbasic catalyst for the synthesis of 2-nitroalkanols from nitroalkanes and aldehydes.10 1

Chebolu, R., Chankeshwara, S.V., Chakraborti, A.K. S 1448 (2008). Motherwell, W.B., Be´gis, G., Cladingboel, D.E., Jerome, L., Sheppard, T.D. T 63, 6462 (2007). 3 Chuprakov, S., Malyshev, D.A., Troﬁmov, A., Gevorgyan, V. JACS 129, 14868 (2007). 4 Ye, L.-W., Sun, X.-L., Wang, Q.-G., Tang, Y. ACIE 46, 5951 (2007). 5 Tran, Y.S., Kwon, O. JACS 129, 12632 (2007). 6 Wallace, D.J., Sidda, R.L., Reamer, R.A. JOC 72, 1051 (2007). 7 Wynne, E.L., Clarkson, G.J., Shipman, M. TL 49, 250 (2008). 8 Yang, Y.-Y., Shou, W.-G., Chen, Z.-B., Hong, D., Wang, Y.-G. JOC 73, 3928 (2008). 9 Cui, S.-L., Wang, J., Wang, Y.-G. OL 10, 13 (2008). 10 Weedon, J.A., Chisholm, J.D. TL 47, 9313 (2006). 2

Triphenylphosphine–dialkyl azodicarboxylate. Epoxides.1 Reaction pathways for the Mitsunobu reaction to convert 1,1-diaryl-2phenylethanediols to epoxides are phosphine-dependent. Retention of conﬁguration at the secondary carbinolic center is observed in reaction mediated by Ph3P–DIAD, while more electron-rich phosphines (e.g., Bu3P) favor products with inversion of conﬁguration.1

Triphenylphosphine –dialkyl azodicarboxylate

O

Bu3P

HO Ph

OH Ar Ar

DIAD

Ph

Ar Ar

O

Ar

Ph3P DIAD

459

Ph

Ar

N-Alkylation.2 Some N-aromatics have been alkylated with ROH, Ph3P, DIAD in MeCN, products such as N-alkylpyridinium and N-methyl-N0 -alkylimidazolium tetraﬂuoroborates are readily isolated. Oximes from alcohols.3 Primary and secondary alcohols are directly converted into oximes on reaction with N-tosylhydroxylamine TBS ether in a conventional Mitsunobu reaction, with succeeding elimination of TsH and desilylation by heating with CsF in MeCN. The reaction conditions are sufﬁciently mild and many functional groups are left unscathed. Cycloaddition.4 An unusual transformation at the conclusion of a stephacidin-A synthesis involves a cycloaddition that is prosecuted by Bu3P –DEAD.

H N

O H HO

O H N Bu3P–DIAD

H N

CH2Cl2

N

H O

40o

O

O

N

N H O stephacidin-A

Dehydration.5 The Mitsunobu reagent (Ph3P –DEAD) successfully achieves selective dehydration of a secondary alcohol (apparently an equatorial cyclohexanol) in the presence of an angular OH group is achieved at room temperature. O

O Ph3P–DEAD

HO

THF 23o

OH

OH

Dialkyl carbonates.6 Treatment of alcohols with Ph3P– DEAD under CO2 in dry DMSO at 90 –1008 leads to formation of carbonates. 1

Garcia-Delgado, N., Riera, A., Verdaguer, X. OL 9, 635 (2007). Petit, S., Azzouz, R., Fruit, C., Bischoff, L., Marsais, F. TL 49, 3663 (2008).

2

460

Triphenylphosphine–bromine

3

Kitahara, K., Toma, T., Shimokawa, J., Fukuyama, T. OL 10, 2259 (2008). Greshock, T.J., Williams, R.M. OL 9, 4255 (2007). 5 Larionov, O.V., Corey, E.J. JACS 130, 2954 (2008). 6 Chaturvedi, D., Mishra, N., Mishra, V. TL 48, 5043 (2007). 4

Triphenylphosphine–bromine. N-Nitrosation. On activation by Ph3P – Br2 the electrophilic NOþ species is brought out of Bu4NNO2. Both secondary and tertiary amines are converted by the reagent mix into nitrosamines, whereas arylhydrazines give aryl azides.1 1

Iranpoor, N., Firouzabadi, H., Nowrouzi, N. TL 49, 4242 (2008).

Triphenylsilyl tetracarbonylcobaltate. Carbonylation.1 Under CO the ring expansion of oxazolines is mediated by Ph3SiCo(CO)4. Actually, BnOH is also required as an additive to generate HCo(CO)4 for the reaction. Chiral precursors of b-amino acids are readily prepared this way. Ar

O CO

+

O

Ar

O

Ph3SiCo(CO)4

N

N

BnOH DME 80o

R

R

1

Byrne, C.M., Church, T.L., Kramer, J.W., Coates, G.W. ACIE 47, 3979 (2008).

Triphosphazene. Beckmann rearrangement.1 The title reagent 1 (i.e., 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-hexachloride) is capable of converting oximes into carboxamides, in either MeCN or hexaﬂuoroisopropanol at 708. Cl

Cl P N N Cl P P Cl N Cl Cl

(1) 1

Hashimoto, M., Obora, Y., Sakaguchi, S., Ishii, Y. JOC 73, 2894 (2008).

Triruthenium dodecacarbonyl. Allylation.1 Linear products are obtained from the Ru-catalyzed allylation of active methylene compounds (deprotonated by LiHMDS) with either primary or secondary allylic acetates. A suitable ligand for the Ru metal is o-diphenylphosphinobenzoic acid. 1

Kawatsura, M., Ata, F., Wada, S., Hayase, S., Uno, H., Itoh, T. CC 298 (2007).

Tris(acetonitrile)cyclopentadienylruthenium(I) hexaﬂuorophosphate

461

Tris(acetonitrile)cyclopentadienylruthenium(I) hexaﬂuorophosphate. Isomerization. Uninterrupted long-chain alkenols undergo isomerization to afford saturated carbonyl compounds on treatment with [CpRu(MeCN)3]PF6 and 1-methyl-2diisopropylphosphino-4-t-butylimidazole (ligand).1 Migration of the double bond over 30 positions has been noted. Substitution. An SN20 substitution operates in the reaction of cinnamyl chloride with PhB(OH)2, when catalyzed by [Cp Ru(MeCN)3]PF6.2 Ene reaction. Unsymmetrical diynes and polyynes combine with 1-alkenes in the fashion of an ene reaction, leading to enynes/enediynes in which the sp-carbon participating in new bonding now bearing an allyl group.3 OR OR Et3Si

Et3Si

n

n

(1)

+

R'

CpRu(MeCN)3PF6

R'

Cyclization. In HOAc the Ru-catalyzed cyclization of 1,6-diynes proceeds with loss of the terminal sp-carbon. If both triple bonds are internal, vic-dialkylidenecyclopentanes are obtained.4 1,7-Diynes seem to behave differently. Cp Ru OAc C

(1)

Z R

HOAc

OAc H Ru Co OAc R

Z

Z

90o

R

Z R

E E

(1) HOAc

E

E

90o

AcO 1

Grotjahn, D.B., Larsen, C.R., Gustafson, J.L., Nair, R., Sharma, A. JACS 129, 9592 (2007). Bouziane, A., Heliou, M., Carboni, B., Carreaux, F., Demerseman, B., Bruneau, C., Renaud, J.-L. CEJ 14, 5630 (2008).

2

462

Tris(dibenzylideneacetone)dipalladium

3

Cho, E.J., Lee, D. JACS 129, 6692 (2007). Gonzalez-Rodriguez, C., Varela, J.A., Castedo, L., Saa, C. JACS 129, 12916 (2007).

4

Tris(dibenzylideneacetone)dipalladium. Suzuki coupling. b,b-Dibromostyrenes undergo Suzuki coupling and the products are readily converted to diarylethynes.1 Note that coupling of 2,2-diﬂuoroethenyl tosylate with ArX furnishes b,b-diﬂuorostyrenes.2 H Br

Ar Br

Ar'

Ar

Suzuki

Bu4NOH

ArB(OH)2

+

F

TsO F

Ar

65o

Br

Ar'

(dba)3Pd2

F

Ar

Cy3PHBF4 H2O, dioxane 100o

F

1-Alkenylpyridinium salts such as 1-(3-keto-1-butenyl)pyridinium tetraﬂuoroborate are active in Suzuki coupling with ArB(OH)2.3 The dimorpholinophosphine 1 is an efﬁcient, air-stable ligand for maintaining (dba)3Pd2 catalytically active in Suzuki coupling,4 whereas chloro(mesityloxy)-t-butylphosphine (2) is good for coupling to form biaryls.5 Ph P

N O

O N O

P Cl

(2)

(1)

2-Arylation of pyridine via coupling of 2-PyB(O-iPr)3Li requires KF as additive and a phosphinous acid ligand.6 Diaryl ketones are produced from ArB(OH)2 and Ar0 CHO in a reaction catalyzed by (dba)3Pd2, using tris(1-naphthyl)phosphine as ligand and the presence of Cs2CO3 in the air.7 Availability of ArB(OH)2 is further assured by the development of a general method for coupling ArCl and bis(pinacolato)diboron.8 Decarboxylative coupling. Diarylethynes are prepared from two ArX and propynoic acid.9 The more reactive ArI is engaged in the ﬁrst stage of the reaction, whereas after decarboxylation of the coupling product the second aryl group (from ArBr) is attached. ArI

+ COOH

(dba)3Pd2 DPPF Bu4NF

Ar'Br

Ar

COOH

90o

Ar

Ar'

Tris(dibenzylideneacetone)dipalladium

463

Arylation and alkenylation. The effectiveness of (dba)3Pd2 for catalyzing Suzuki coupling and N-arylation is further demonstrated in an elaboration of carbazoles.10 B(OH)2

I

+ Br Ph2P

OMe

H2N Cs2CO3

(dba)3Pd2 (1)

PhMe 100o; t-BuONa

(1) N H

Another carbazole synthesis involves a twofold N-arylation, as shown by the preparation of an intermediate for murrayazoline.11

OMOM OMOM Br Br

(dba)3Pd2

t-BuOK

+

H2N

N

PhMe 130o

O

O Cy2P

O

O 59%

3-Substituted indoles are available from coupling of o-bromoiodoarenes with allylic amines.12 The catalyst system is capable of inducing further N-arylation of the resulting indoles. Double N-arylation and S-arylation complete the assembly of phenothiazines13 from an amine and two aryl halides, one of the halides being an o-bromoarenethiol.

I

SH

(dba)3Pd2

+ Br

Br RNH2

R'

DPPF t-BuOK/PhMe w

S N R

R'

A study of N-arylation of amides has shown the effect of product yields on critical structural feature of the X-Phos-type (2-di-t-butylphosphinobiaryl) ligand. It appears that

464

Tris(dibenzylideneacetone)dipalladium

a methyl group C-3 (ortho to the phosphine substituent) changes the outward orientation of the amido-Pd to an inward conformation.14 Cl

NHCOPh

(dba)3Pd2

+ PhCONH2

Cs2CO3

MeO

MeO

t-BuOH ligand

R = Me R=H

ligand subst. OMe

R

P Pd N

H

95% 9%

MeO

O H2N

Pd P O

preferred structures of + +

The coupling of ArCl with benzophenone imine is a fast reaction, therefore it represents an option for preparation of arylamines, as the products are easily hydrolyzed.15 A simple protocol also avails for the preparation of the N-Boc derivatives of N-alkenylhydrazines from N-haloalkenes.16 Miscellaneous coupling reactions. Heck reaction and subsequent intramolecular Michael reaction are probably involved in the aminoarylation of 3-cyclohexenones.17

Br

R

R

O

(dba)3Pd2

+

DPPF, K2CO3

NH2

O

PhMe

N H H

The reaction of tosylhydrazones with ArX under the inﬂuence of (dba)3Pd2 –X-Phos performs the equivalent of an arylative Shapiro reaction.18 A mixture of carbonyl compounds and TsNHNH2 can be employed in lieu of the tosyhydrazones.19 Ar

O + TsNHNH 2 N R

(dba)3Pd2 –t -BuOLi

+ ArX

N R Cy2P

Tris(dibenzylideneacetone)dipalladium

465

t-Butyl 3-sulﬁnylpropanoates release the sulﬁnyl group for coupling with ArI to form aryl sulfoxides (and with a chiral ferrocenylphosphine ligand present asymmetric induction has been observed – to 83% ee).20 Assisted by KF hexamethyldisilane supplies the Me3Si group to form ArSiMe3.21 Two synthetically interesting processes are the SN20 reaction of the esters of allenyl carbinols with organozinc reagents to generate conjugated dienes,22 and the benzologue version (1,5-transpositional displacement) involving allyltributylstannane.23

R R

(dba)3Pd2

+ R'ZnBr

AcO C

DPPF PhMe 23o

R'

Cl (dba)3Pd2

+

Ph3P CH2Cl2, 25o

Bu3Sn

84%

The Heck reaction of oximes derived from allyl ketones is followed by cyclization to give isoxazolines.24 An intramolecular Heck reaction of substituted 6-chloro-1-hexenes readily affords the methylenecyclopentanes.25

NOH

+

R

(dba)3Pd2

ArBr

N O

Xantphos

R

t-BuONa, PhMe

Ar

105o

(MeO-dba)3Pd2

R

Cl

N

N ..

R

MeCN, 65o

Allylation. 2,3-Disubstituted indoles are allylated at C-3 by the Pd-catalyzed reaction with an alkyl allyl carbonate.26 The allyl group of allyl o-/p-nitroarylacetates is recaptured via a sp 3-sp 3 coupling after decarboxylation.27

466

Tris(dibenzylideneacetone)dipalladium

R

R'

R

O

R'

(dba)3Pd2 rac-BINAP

O NO2

PhMe

NO2

Carbonylation. N,O-Acetals in which the amino nitrogen atom is acylated are converted into O-chelated palladium species by replacing the oxy group (e.g., PhO group). Incorporation of CO completes the homologation process.28 Ar PhO

Ar NBn

O

Ar'

Ar

(dba)3Pd2

L2Pd

BF3 · OEt2 MeCN 80o

PhO

CO

NBn O

AlF3

PhOOC

Ar'

NBn O

Ar'

Addition and cycloaddition. In the (dba)3Pd2-catalyzed hydrostannylation of alkynes the regiochemistry is controlled by the phosphine ligands. (E)-1-Tributylstannylalkenes are produced preponderantly in the presence of Cy3P or t-Bu3P, but much more 2-stannyl1-alkenes are obtained with Ph3P.29 p-Allylplladium zwitterions are generated from 2-vinyl-1,1-cyclopropanedicarboxylic esters on treatment with an analogue of (dba)3Pd2. These species can be trapped by aldehydes.30 MeOOC COOMe

COOMe

(MeO-dba)3Pd2

+

RCHO

bathiphenanthroline

COOMe

O

R

Rearrangement. 1-Allenylcyclobutanols undergo Wagner –Meerwein rearrangement to afford 2-vinylcyclopentanones. The rearrangement can be rendered asymmetric.31 OH C OBn

R O

H N

N H

O

(dba)3Pd2 (1)

Et3N, PhCOOH ClCH2CH2Cl 60o

PPh2 Ph2P

O

(1)

OBn R

Tris(dibenzylideneacetone)dipalladium – chloroform

467

1

Chelucci, G., Capitta, F., Baldino, S., Pinna, G.A. TL 48, 6514 (2007). Gogsig, T.M., Sobjerg, L.S., Lindhardt, A.T., Jensen, K.L., Skrydstrup, T. JOC 73, 3404 (2008). 3 Buszek, K.R., Brown, N. OL 9, 707 (2007). 4 Cho, S.-D., Kim, H.-K., Yim, H.-s., Kim, M.-R., Lee, J.-K., Kim, J.-J., Yoon, Y.-J. T 63, 1345 (2007). 5 Mai, W., Lv, G., Gao, L. SL 2247 (2007). 6 Billingsley, K.L., Buchwald, S.L. ACIE 47, 4695 (2008). 7 Qin, C., Chen, L., Wu, H., Cheng, J., Zhang, Q., Zuo, B., Su, W., Ding, J. TL 49, 1884 (2008). 8 Billingsley, K.L., Barder, T.E., Buchwald, S.L. ACIE 46, 5359 (2007). 9 Moon, J., Jeong, M., Nam, H., Ju, J., Moon, J.H., Jung, H.M., Lee, S. OL 10, 945 (2008). 10 Kitamura, Y., Yoshikawa, S., Furuta, T., Kan, T. SL 377 (2008). 11 Ueno, A., Kitawaki, T., Chida, N. OL 10, 1999 (2008). 12 Jensen, T., Pedersen, H., Bang-Andersen, B., Madsen, R., Jorgensen, M. ACIE 47, 888 (2008). 13 Dahl, T., Tornoe, C.W., Bang-Andersen, B., Jorgensen, M. ACIE 47, 1726 (2008). 14 Ikawa, T., Barder, T.E., Biscoe, M.R., Buchwald, S.L. JACS 129, 13001 (2007). 15 Grossman, O., Rueck-Braun, K., Gelman, D. S 537 (2008). 16 Barluenga, L., Moriel, P., Aznar, F., Valdes, C. OL 9, 275 (2007). 17 Hyde, A.M., Buchwald, S.L. ACIE 47, 177 (2008). 18 Barluenga, J., Moriel, P., Valdes, C., Aznar, F. ACIE 46, 5587 (2007). 19 Barluenga, J., Tomas-Gamasa, M., Moriel, P., Aznar, F., Valdes, C. CEJ 14, 4792 (2008). 20 Maitro, G., Vogel, S., Sadaoui, M., Prestat, G., Madec, D., Poli, G. OL 9, 5493 (2007). 21 McNeill, E., Barder, T.E., Buchwald, S.L. OL 9, 3785 (2007). 22 Schneekloth J.S. Jr, Pucheault, M., Cross, C.M. EJOC 40 (2007). 23 Lu, S., Xu, Z., Bao, M., Yamamoto, Y. ACIE 47, 4366 (2008). 24 Jiang, D., Peng, J., Chen, Y. OL 10, 1695 (2008). 25 Firmansjah, L., Fu, G.C. JACS 129, 11340 (2007). 26 Kagawa, N., Malerich, J.P., Rawal, V.H. OL 10, 2381 (2008). 27 Waetzig, S.R., Tunge, J.A. JACS 129, 14860 (2007). 28 Lu, Y., Arndtsen, B.A. OL 9, 4395 (2007). 29 Darwish, A., Lang, A., Kim, T., Chong, J.M. OL 10, 861 (2008). 30 Parsons, A.T., Campbell, M.J., Johnson, J.S. OL 10, 2541 (2008). 31 Trost, B.M., Xie, J. JACS 130, 6231 (2008). 2

Tris(dibenzylideneacetone)dipalladium –chloroform. Allylic substitution. Allylic carbonates are found to undergo substitution by benzylamine, there is regiochemical dependence on solvent.1 NHBn R OCOOMe

COEt

(dba)3Pd2 · CHCl3

R

(Solv)

COEt

+

BnNH2 R

(MeCN)

(THF) NHBn CHMe COEt

Two complementary methods for allylation of arene derivatives are: Suzuki coupling with allyl acetates,2 and converting allyl acetates to allylindium reagents in situ for couping with ArX.3

468

Tris(dibenzylideneacetone)dipalladium – chloroform

Coupling reactions. Insertion of the trimethylsilylcarbenoid into an ArZBr bond generates benzylpalladium reagents. Transfer of the Pd unit to a new carbon site starts another homologation reaction.4

+ Me3SiCHN2

Br

SiMe3 CHSiMe3

(dba)3Pd2 · CHCl3 Ph3P, K2CO3

COOEt

COOEt

THF

Chain elongation and amination occur on alkenyl iodides, when amines are added as co-reactants.5

R

R +

N

(dba)3Pd2 · CHCl3

I

N H

Ph3P

SiMe3

+ Me3SiCHN2

a-Amino ketones are prepared from RSnBu3, CO, imines (and ClCOOR0 for trapping the amino group) at room temperature. The products serve as intermediates of imidazolones.6 R' CO RSnBu3

Cl-COOR" N

+

Bu4NBr

+

R"OOC O NR'

(dba)3Pd2 · CHCl3

Ar

MeCN, CH2Cl2

R

Ar

Suzuki coupling of unactivated ArCl is effectively conducted with the Pd complex in the presence of a bowl-shaped phosphine ligand 1; the deeper the bowl, the higher the effectiveness.7

3

(1)

P

Tris(trimethylsilyl)silane

469

Rearrangement. (2-Pyridinioethynyl)triphenylborate undergoes 1,2-phenyl migration while the NZH proton is transferred to the proximal sp-carbon.8

(dba)3Pd2 · CHCl3

N H

BPh3

N

Ar3P THF

Ph

B

Ph

Ph 1

Benfatti, F., Cardillo, G., Gentilucci, L., Mosconi, E., Tolomelli, A. OL 10, 2425 (2008). Pola´cˇkova´, V., Toma, Sˇ., Kappe, C.O. T 63, 8742 (2007). 3 Seomoon, D., Lee, P.H. JOC 73, 1165 (2008). 4 Kudirka, R., Van Vranken, D.L. JOC 73, 3585 (2008). 5 Devine, S.K.J., Van Vranken, D.L. OL 9, 2047 (2007). 6 Siamaki, A.R., Black, D.A., Arndtsen, B.A. JOC 73, 1135 (2008). 7 Ohta, H., Tokunaga, M., Obora, Y., Iwai, T., Iwasawa, T., Fujihara, T., Tsuji, Y. OL 9, 89 (2007). 8 Ishida, N., Narumi, M., Murakami, M. OL 10, 1279 (2008). 2

Tris(pentaﬂuorophenyl)borane. Tritylation.1 Primary and secondary alcohols can be tritylated with TrOH in CH2Cl2 at room temperature with (C6F5)3B as catalyst. 1

Reddy, C.R., Rajesh, G., Balaji, S.V., Chethan, N. TL 49, 970 (2008).

Tris(trimethylsilyl)silane. Alkenylsilanes.1 Addition of (Me3Si)3SiH to 1-alkynes in the presence of a Rh(I) complex furnishes the (E)-1-silylalkenes, whereas the (Z)-isomers are obtained from formal group exchange reaction starting from (Z)-1-alkenyl sulfones. These alkenylsilanes can be used in Hiyama coupling after treatment with alkaline H2O2. R

SO2Ph

(Me3Si)3SiH

R

Si(SiMe3)3

AIBN PhH

Si(SiMe3)3

(Me3Si)3SiH

R

(Ph3P)3RhCl

R

Oxygenation.2 To functionalize a tertiary carbon atom adjacent to an alcohol via derivatization of the OH group to a bromomethyldimethylsilyl ether, radical generation to conduct hydrogen atom abstraction, with Cu(OAc)2 to provide the necessary functionalizing element is involved.

470

Tungsten carbene and carbyne complexes

O

O Br

N O

OSiMe3

Si (Me3Si)3SiH AIBN, Cu(OAc)2

NMe

wet ClCH2CH2Cl

NMe

O

80o

OAc

OR O

N

OAc R = H 25% + R = Ac 42% (+ -OH isomer 6%)

1

Wang, Z., Pitteloud, J.-P., Montes, L., Rapp, M., Derane, D., Wnuk, S.F. T 64, 5322 (2008). Overman, L.E., Sato, T. OL 9, 5267 (2007).

2

Tungsten carbene and carbyne complexes. Dihydropyran formation. Cyclization of 4-alkynols is induced by the tungsten version of a Fischer carbene complex without the need of UV irradiation, its application to a synthetic approach to altromycin-B disaccharide has been demonstrated.1 O

HO

W(CO)5

O

OMOM OTIPS

O

CbzNH

Et3N THF 40o

CbzNH

Alkyne metathesis. room temperature.2

O

OMe

O

OMOM OTIPS

The complex 1 is a valuable catalyst for alkyne metathesis at

F3C

CF3 O

F3C

N W

N

N

O CF3

(1) 1

Ko, B., McDonald, F.E. OL 9, 1737 (2007). Beer, S., Hrib, C.G., Jones, P.G., Brandhorst, K., Grunenberg, J., Tamm, M. ACIE 46, 8890 (2007).

2

Tungsten hexacarbonyl. Cyclization. Activation of alkynes by W(CO)6 under photoirradiation can provoke participation of an amine in the vicinity. A structural transformation of o-cycloaminoarylalkynes upon the treatment consists of cyclization with reorganization of ring system.1

Tungsten hexacarbonyl

N

N

W(CO)6

471

N R R

[W]

R

Siloxycycloalkenes substituted by a propargylamino group at the allylic position cyclize by two different modes, depending on the solvent.2 O

TIPSO R'

O

R'

R'

W(CO)6

N H R

N R solvent dependence:

N H R (PhMe)

(THF)

A formal [4þ1]cycloaddition of a diene unit and a terminal alkyne is mediated by W(CO)6.3 Most interestingly, the addition of Bu3N to the reaction medium changes the reaction course drmatically. TIPSO W(CO)6

TIPSO

Ms N

H Ms N

PhMe

Ph

H

Ph TIPSO hv, W(CO)6

NMs

Bu3N/PhMe

Ph 1

Takaya, J., Udagawa, S., Kusama, H., Iwasawa, N. ACIE 47, 4906 (2008). Grandmarre, A., Kusama, H., Iwasawa, N. CL 36, 66 (2007). 3 Onizawa, Y., Kusama, H., Iwasawa, N. JACS 130, 802 (2008). 2

H

U Urea – hydrogen peroxide. Oxidation.1 Oxidation of imines to nitrones by this reagent is catalyzed by MeReO3. 1

Soldaini, G., Cardona, F., Goti, A. OL 9, 473 (2007).

Urea nitrate. Nitration.1 Regioselective mononitration (but no further) of moderately deactivated arenes is accomplished with urea nitrate or nitrourea, despite their use in excess. 1

Almog, J., Klein, A., Sokol, A., Sasson, Y., Sonenfeld, D., Tamiri, T. TL 47, 8651 (2006).

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 473

W Water. Deacetalization.1 Merely deionized water is the required reagent for removing acetal protection under microwave irradiation. 1

Procopio, A., Gaspari, M., Nardi, M., Oliverio, M., Tagarelli, A., Sindona, G. TL 48, 8623 (2007).

Wittig reagents. Methylenation.1 The crystalline, salt-free Ph3PvCH2, as described 36 years ago,1 is critical for overcoming the difﬁculty in methylenating the cyclononenone carbonyl in a synthesis of coraxeniolide-A.2

O

O H

O

Ph3P=

O

H

O O

(salt free)

H

O 61% coraxeniolide-A 1

Schmidbauer, H., Stuhler, H., Vornberger, W. CB 105, 1084 (1972). Larionov, O.V., Corey, E.J. JACS 130, 2954 (2008).

2

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 475

Y Ytterbium(III) triﬂate. Condensations. Conjugated thioesters are made from aldehydes and monothioesters of malonic acid at room temperature using Yb(OTf)3 as catalyst. Arylacetaldehydes afford thioesters containing a benzylic double bond.1 Allylation. N-(d-Hydroxyalkyl)ureas in which the b-position is branching out by a methylene group are synthesized by Lewis acid-catalyzed reaction of stannylated allylureas. Different diastereomers can be obtained by proper choice of the Lewis acid.2 OH Yb(OTf)3

R

Et2O

NHCONMe2

25o

SnBu3

85–93% syn

RCHO + NHCONMe2

OH SnCl4

R

CH2Cl2

NHCONMe2

0o

87–100% anti

Heterocycles. In the presence of Yb(OTf)3 epoxides are readily transformed into oxazolidines3 and 2-iminothiazolidines4 by reaction with imines and thioureas, respectively. 2-(2-Aminoxyethyl)cyclopropane-1,1-dicarboxylic esters condense with aldehydes to give bicyclic isoxazolidines.5 O N

Yb(OTf)3 ; RCHO

O H2N

R MeOOC

MeOOC COOMe

O N

RCHO; Yb(OTf)3

R MeOOC

H COOMe

H COOMe

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 477

478

Yttrium(III) chloride

An eight-membered lactam is formed on treatment of the amide derived from tryptamine and epoxycinnamic acid.6 NH

NH O

O

Yb(OTf)3

OH

CH2Cl2

N Ph O H

N H

μw

Ph 37%

Isobenzofurans and activated cyclopropanes condense to give an oxabridged ring system.7 Ph O

E

Ph COOMe COOMe O

E Yb(OTf)3

+

CH2Cl2

Ar

Ph Ar

Ph E = COOMe 1

Berrue, F., Antoniotti, S., Thomas, O.P., Amade, P. EJOC 1743 (2007). Nishigaichi, Y., Tamura, K., Ueda, N., Iwamoto, H., Takuwa, A. TL 49, 2124 (2008). 3 Yu, C., Dai, X., Su, W. SL 646 (2007). 4 Su, W., Liu, C., Shan, W. SL 725 (2008). 5 Jackson, S.K., Karadeolian, A., Driega, A.B., Kerr, M.A. JACS 130, 4196 (2008). 6 Johansen, M.B., Leduc, A.B., Kerr, M.A. SL 2593 (2007). 7 Ivanova, O.A., Budynina, E.M., Grishin, Y.K., Trushkov, I.V., Verteletskii, P.V. ACIE 47, 1107 (2008). 2

Yttrium(III) chloride. Cyclopentadienylyttrium dihydride. Consecutive reaction of YCl3 with CpNa and Dibal-H leads to CyYH2, which adds to CH2vCHMgCl readily. The dimetallated ethane thus generated is a valuable reagent that can be used to functionalize and homologate alkynes and transforming esters into cyclopropanols (Kulinkovich reaction).1 CyNa;

YCl3

Dibal-H

MgCl

CpYH2

MgCl 2

CpY RCOOEt; Ph

H+

SiMe3

R HO

Ph Me3Si

1

Tanaka, R., Sanjiki, H., Urabe, H. JACS 130, 2904 (2008).

M M'

Yttrium(III) triﬂate

479

Yttrium(III) triﬂate. Condensation. In the presence of Y(OTf)3 microwave irradiation of a mixture of cinnamic acid and resorcinol leads to a 4-aryl-3,4-dihydrocoumarin.1 1

Rodrigues-Santos, C.E., Echevarria, A. TL 48, 4505 (2007).

Z Zeolites. Condensation. Cinnamic acid condenses with benzene in zeolites, but the reaction pattern depends on the type of the zeolite used.1 O H-USY

HOOC

Ph Ph

+ PhH

H-ZSM5

Ph

Ph

1

Chassaing, S., Kumarraja, M., Pale, P., Sommer, J. OL 9, 3889 (2007).

Zinc. Organozinc chlorides. To avoid generation of dibenzyls during preparation of benzylic zinc reagents from ArCH2Cl in THF, a protocol exploits the beneﬁcial effect of LiCl.1 Allylzinc chlorides are similarly available, and they add to carbonyl compounds with excellent diastereoselectivity.2 OH

ZnCl + Ar

Ar

O 99%

Reduction. N-Hydroxymaleimides are reduced to succinimides without affecting the N-hydroxyl group by Zn– HOAc. The reduction provides cis-isomers from fully substituted maleimides.3

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 481

482

Zinc

O

O R

R Zn

O

N OH

O

HOAc 25o

O

N OH

O

The triple bond of a propargylic sulfone is reduced to give a (Z)-allylic sulfone, on treatment with zinc in a mixture of THF and aqueous NH4Cl at room temperature.4 HO HO

SO2Ph

R

Zn, NH4Cl THF, H2O

R

SO2Ph (Z : E 25 : 1)

O2SPh

Zn, NH4Cl

O2SPh SO2Ph

THF, H2O

SO2Ph

(Z : E 5.2 : 1)

Organoazides are reduced by Zn–NH4Cl in hot aqueous EtOH and react with b-keto esters in situ to give b-amino-a,b-unsaturated esters.5 Reductive alkylation. A previously reported N-methylation method for secondary amines with aqueous HCHO, Zn and HOAc is applicable to amino acids. Mono- or dimethylation can be controlled by adjustment of pH, reagent stoichiometry, and reaction time.6 a-Branched amines can be prepared from amines, RCHO and alkyl halides by the action of zinc in MeCN.7 Amido carbenoids. Acetals of N-formyllactams (as well as imides and oxazolinones) engage in cyclopropanation with alkenes in the presence of Zn and CuCl.8 O

O N CH(OEt)2

1

Zn

+

CuCl

R

Metzger, A., Schade, M.A., Knochel, P. OL 10, 1107 (2008). Ren, H., Dunet, G., Mayer, P., Knochel, P. JACS 129, 5376 (2007). 3 Cheng, C.-F., Lai, Z.-C., Lee, Y.-J. T 64, 4347 (2008). 4 Sheldrake, H.M., Wallace, T.W. TL 48, 4407 (2007). 2

N

R

Zinc chloride

483

5

Prabhakar, A.S., Sashikanth, S., Reddy, P.P., Cherukupally, P. TL 48, 8709 (2007). da Silva, R.A., Estevam, I.H.S., Bieber, L.W. TL 48, 7680 (2007). 7 Sengmany, S., Le Gall, E., Troupel, M. SL 1031 (2008). 8 Motherwell, W.B., Begis, G., Cladingboel, D.E., Jerome, L., Sheppard, T.D. T 63, 6462 (2007). 6

Zinc bromide. Propargylmagnesium bromides.1 In preparation of Grignard reagents from propargylic bromides and Mg the use of ZnBr2 as catalyst is preferable to HgCl2 for apparent reasons (toxicity). 1

Acharya, H.P., Miyoshi, K., Kobayashi, Y. OL 9, 3535 (2007).

Zinc chloride. Furans. Propargyl ketones cycloisomerize to provide furans at room temperature, using ZnCl2 as promoter.1

R

O

ZnCl2

R" R'

O

R

R"

CH2Cl2 22o

R'

Beckmann rearrangement. Ketoximes rearrange on heating with ZnCl2 and TsOH in MeCN.2 Reductive silylation. Carbonyl compounds are converted into silyl ethers by a mixture of R3SiCl, CaH2, and ZnCl2 in THF.3

b-Amido ketones.4 When ketones, aldehydes and nitriles are mixed with ZnCl2 and SiCl4 they condense to provide b-amido ketones. A Ritter reaction following aldol reaction accounts for the results.

O NC R'"

O + R R'

1

O

HN

R"'

ZnCl2 –SiCl 4

OHC

R"

CH2Cl2

R

R" R'

Sniady, A., Durham, A., Morreale, M.S., Wheeler, K.A., Dembinski, R. OL 9, 1175 (2007). Xiao, L., Xia, C., Chen, J. TL 48, 7218 (2007). 3 Tsuhako, A., He, J.-Q., Mihara, M., Saino, N., Okamoto, S. TL 48, 9120 (2007). 4 Salama, T.A., Elmorsy, S.S., Khalil, A.-G.M., Ismail, M.A. TL 48, 6199 (2007). 2

484

Zinc iodide

Zinc iodide. Cyclization. Treatment of conjugate dienyl azides with ZnI2 gives pyrroles.1 R'

R' R

ZnI2

COOR"

N3

CH2Cl2

R

COOR"

N H

25o

Indolizidinones are created from 6-(3-benzenesulﬁnylpropyl)-2-piperidone when exposed to ZnI2 and a ketene silyl ether.2 This method3 entails a Pummerer rearrangement to generate a sulfur-stabilized carbocation for inducing the ring closure (NZC bond formation). ZnI2

NH O

N

OMe OTBS

S Ph

SPh

O

MeCN

O

85%

1

Dong, H., Shen, M., Redford, J.E., Stokes, B.J., Pumphrey, A.L., Driver, T.G. OL 9, 5191 (2007). Kuhakarn, C., Seehasombat, P., Jaipetch, T., Pohmakotr, M., Reutrakul, V. T 64, 1663 (2008). 3 Kita, Y., Yasuda, H., Tamura, O., Itoh, F., Tamura, Y. TL 25, 4681 (1984). 2

Zinc oxide. Acylation.1 Zinc oxide is found to be a good catalyst for acylation of ferrocene. 1

Wang, R., Hong, X., Shan, Z. TL 49, 636 (2008).

Zinc triﬂate. Silylation.1 With Zn(OTf)2 as catalyst 1-alkynes are silylated by a mixture of Me3SiOTf and Et3N at room temperature. Michael reaction.2 Great activity is exhibited by Zn(OTf)2 for promoting the Mukaiyama version of the Michael addition involving the enol silyl ether of methyl a-diazoacetoacetate and conjugated cycloalkenones. OTBS

O

TBSO + R

COOMe N2

O

Zn(OTf)2

COOMe

CH2Cl2 0-25o

R

N2

Zirconium(IV) bromide

485

Heterocycle synthesis. Arylhydrazines and 1-alkynes react to form N-heterocycles. 1-Aryl-2-pyrazolene are produced from 3-butynol,3 whereas 2-methyl-3-alkylindoles are obtained from other 1-alkynes.4

THF

OH R'

+ N R

NNHAr

Zn(OTf)2

ArNHNH2

+

NH2

100o

N N

Ar

OH R'

Zn(OTf)2 THF 100o

N R

Maleimide formation from 2,3-dienoic esters and isonitriles is a cycloaddition catalyzed by Zn(OTf)2 under O2.5 Ar MeOOC

N C

Zn(OTf)2

+ N Ts

Ar N

O

O

THF– H2O O2 50o

N Ts

1

Rahaim R.J., Jr, Shaw, J.T. JOC 73, 2912 (2008). Liu, Y., Zhang, Y., Jee, N., Doyle, M.P. OL 10, 1605 (2008). 3 Alex, K., Tillack, A., Schwarz, N., Beller, M. OL 10, 2377 (2008). 4 Alex, K., Tillack, A., Schwarz, N., Beller, M. ACIE 47, 2304 (2008). 5 Li, Y., Zou, H., Gong, J., Xiang, J., Luo, T., Quan, J., Wang, G., Yang, Z. OL 9, 4057 (2007). 2

Zirconia, sulfated. Mannich reaction.1 Reaction between ketene silyl acetals and aldimines occurs in the presence of sulfated zirconia in MeCN at room temperature. The reusable solid catalyst is easily recovered. 1

Wang, S., Matsumura, S., Toshima, K. TL 48, 6449 (2007).

Zirconium(IV) bromide. Bromination.1 Active arenes such as phenols, aryl ethers, and anilines are brominated by ZrBr4 in the presence of diisopropyl azodicarboxylate in CH2Cl2. A free para position is the preferred site for bromination. 1

Stropnik, T., Bombek, S., Kocevar, M., Polanc, S. TL 49, 1729 (2008).

486

Zirconium(IV) t-butoxide

Zirconium(IV) t-butoxide. Substitution.1 A stepwise reaction of carbonate esters with amines leads to unsymmetrical ureas. Using (t-BuO)4Zr as catalyst the formation of carbamates is achieved at 80o, and the second step is performed under microwave irradiation. Different additives are indicated for the two steps, they are 2-pyridone and 2-quinolone, respectively. OR O OR

(t-BuO)4Zr

NHR' O

R'NH2, N 80

O

R"NH2,

OR

OH

NHR'

(t-BuO)4Zr

NHR" N

w

o

OH

1

Han, C., Porco Jr, J.A. OL 9, 1517 (2007).

Zirconium (IV) chloride. Friedel-Crafts alkylation.1 Cyclization of 2-(2-arylethyl)cyclohexanols usually gives cis-AB tricyclic compounds. The trans-fused isomers, which are potential precursors of C-aromatic tricyclic diterpenes, are accessible when ZrCl4 is used to induce the cyclization. O

OLi MeMgCl;

O

CN

NC

OH

OLi

ArCH2MgCl

Ar

Mg

Ar

MeI

CN

1

Fleming, F.F., Wei, G., Steward, O.W. JOC 73, 3674 (2008).

Zirconium tetrakis(dimethylamide). Hydroamination. A catalyst (1) for intramolecular hydroamination is readily made from (Me2N)4Zr by ligand exchange.1 Alternatively, a chiral 6,60 -dimethyl-2,20 amidobiphenyl may be used as ligand.2

P S Zr

NMe2 NMe2

P S

(1) 1

Kim, H., Livinghouse, T., Lee, P.H. T 64, 2525 (2008). Wood, M.C., Leitch, D.C., Yeung, C.S., Kozak, J.A., Schafer, L.L. ACIE 46, 354 (2007).

2

Zirconocene, Zr-alkylated

487

Zirconocene, Zr-alkylated. Reductive coupling. After transformation of Cp2ZrBu2 into Cp2ZrEt2 by reaction with ethylene the sequential treatment with alkynes leads to zirconacyclopentadienes possessing more varied substituents. On oxidative opening of the zironacycles with NCS and CuCl reagents for alkenylcuprations are produced. Dienylcopper species are useful for further synthetic purposes, for example, preparation of linear polyenes.1 R BuLi;

Cp2ZrCl2

Cp2ZrEt2

CH2=CH2

R

R;

Ar

Ar

R

Cp2Zr

Ar Ar NCS, CuCl

R

R E

R

E E

Cl

E

[Cu] Ar

R [Cu]

Cl Ar

Ar

Ar

Ts; H+

R

R E

E

Cl Ar

Ar

Ts

A synthesis of octacyclopropylcubanes2 from dicyclopropylethyne requires three steps, starting from reaction with Cp2ZrBu2.

Cp2ZrCl2 BuLi

I2

ZrCp2

CuCl

h

48%

20o

488

Zirconocene dichloride

1

Kanno, K.-I., Igarashi, E., Zhou, L., Nakajima, K., Takahashi, T. JACS 130, 5624 (2008). De Meijere, A., Redlich, S., Frank, D., Magull, J., Hofmeister, A., Menzel, H., Ko¨nig, B., Svoboda, V. ACIE 46, 4574 (2007).

2

Zirconocene dichloride. Homopropargylic alcohols.1 Silver(I) alkynides in a CH2Cl2 solution or suspension prepared from alkynes and AgNO3 are transformed into alkynylzirconocenes, which can be used to attack epoxides.

R

R +

O

Cp2ZrCl2

R'

Ag

TfO

AgOTf

R

ZrCp2

OH

O

R'

R'

Addition reactions. The mixed alane generated in situ from Me3Al and isobutylaluminoxane adds to 1-alkynes to afford 2-methyl-1-alkenylaluminum reagents. This process has been applied to a synthesis of coenzyme Q10.2 R Me3Al – Cp2ZrCl2

R

Al

(i-BuAlO)n PhMe 25o

The alkenylalanes can be converted into trisubstituted enolates by peroxyzinc species,3 thereby endorsing many further synthetic opportunities.

Me3Al – Cp2ZrCl2

R

R

R

t-BuOOZnMe

OSiMe3

O[M]

Better regiocontrol for carboalumination is obtained using (ethylenebisindenyl)zirconium dichloride, the benzologue of Cp2ZrCl2, while adding 5 mol% of MAO to accelerate the reaction.4 After forming Cp2Zr(CH2vCH2) by Grignard reaction of Cp2ZrCl2 to transform dialkynyldiarylsilanes into silacyclobutenes, conjugated dienes are produced on protodesilylation with TBAF .5 Ph

Ph

Ar

Cp2Zr(CH2— —CH2)

Si R

THF –60 o

R'

R

R

Ar TBAF

Si R'

THF

R'

Zirconocene hydrochloride

489

Hydration of fullerene at room temperature is catalyzed by Cp2MCl2 (MvZr, 73%; Hf, 75%; Ti, 66%). The yield is increased to 90% when the reaction is run at 808 at shorter reaction time (1 hr). Transition metal salts do not have this catalytic activity.6 1

Albert, B.J., Koide, K. JOC 73, 1093 (2008). Lipshutz, B.H., Butler, T., Lower, A., Servesko, J. OL 9, 3737 (2007). 3 DeBerg, J.R., Spivey, K.M., Ready, J.M. JACS 130, 7828 (2008). 4 Lipshutz, B.H., Butler, T., Lower, A. JACS 128, 15396 (2006). 5 Jin, C.K., Yamada, T., Sano, S., Shiro, M., Nagao, Y. TL 48, 3671 (2007). 6 Tuktarov, A., Akhmetov, A.R., Pudas, M., Ibragimov, A.G., Dzhemilov, U.M. TL 49, 808 (2008). 2

Zirconocene hydrochloride. Hydrozirconation. Hydrozirconation of nitriles by Cp2Zr(H)Cl followed by reaction with RCOCl and quenched with nucleophiles gives rise to functionalized amides such as acylaminals and acyl hemiaminals (by adding alcohols and water, respectively).1 R Cp2ZrH(Cl)

R CN

R

R'COCl

N

NZrCp

O

R' MeOH

R MeO

NH O

R'

Synthesis of homologated allylic alcohols from propargylic alcohols is easily performed via hydrozirconated intermediates. Chain elongation or functionalization at either end of the original triple bond is feasible because hydrozirconation of the derived alkoxides becomes group-directed.2

OH Cp2Zr(H)Cl; [R' +]

R

R'

OH R

OH MeLi; Cp2Zr(H)Cl; ZnCl2,

[R'+]

R R'

490

Zirconyl chloride

With Cp2Zr(H)Cl to catalyze the addition of methylpentanediolatoborane to alkynes, air-stable alkenylborates are formed.3

R

+

O HB

Cp2Zr(H)Cl o

O

25

R

O B

O

1

Wan, S., Green, M.E., Park, J.-H., Floreancig, P.E. OL 9, 5385 (2007). Zhang, D., Ready, J.M. JACS 129, 12088 (2007). 3 PraveenGanesh, N., d’Hondt, S., Chavant, P.Y. JOC 72, 4510 (2007). 2

Zirconyl chloride. Allylation. With promotion by ZrOCl2 . 8H2O allylation of aldehydes with allyltributylstannane is accomplished in water. a-Branched homoallylic amines are obtained with a mixture of RCHO and ArNH2.1 1

Shen, W., Wang, L.-M., Feng, J.-J., Tian, H. TL 49, 4047 (2008).

AUTHOR INDEX Abad, A., 211 Abbasi-Ghadim, H., 437 Abboud, K.A., 149 Abdel-Hadi, M., 237, 343 Abdel-Maksoud, A.A., 203 Abdi, D., 64 Abdi, S.H.R., 454 Abe, M., 312 Abe, Y., 57, 255 Abecassis, K., 153 Abela, A.R., 349 Abell, J.P., 135 Abou, A., 280 Abramite, J.A., 8 Abu, Sohel, S.M., 365 Aburano, D., 198 Aburatani, S., 241 Acharya, H.P., 234, 483 Acharya, J., 368 Ackermann, J., 32 Ackermann, L., 39, 337, 401–402 Adak, L., 87 Adams, B., 200 Adams, H., 90, 234 Adjiman, C.S., 400 Adolfsson, H., 152 Adonin, N.Yu., 349 Adrio, J., 291 Afonso, C.A.M., 390 Aggarwal, V.K., 90, 130, 306 Agosti, A., 301 Agostinho, M., 135 Agrawal, S., 454 Aguiar, L.C.S., 242 Aguilar, E., 221 Aguilar-Aguilar, A., 36 Aguinaldo, G.T., 400 Aguirre, A., 306 Aguirre, G., 152 Ahlford, K., 152

Ahlquist, M., 187 Ahmed, M., 45 Ahmad, M., 198 Ahmad, O.K., 452 Ahmed, Z., 23 Ahn, H.R., 92 Ai, T., 14 Aikawa, H., 221 Aikawa, K., 123, 135 Aili, D., 163 Aillaud, I., 17 Aissa, C., 47 Aizawa, T., 43 Akai, S., 222, 452 Akalay, D., 144 Akamanchi, K.G., 263 Akana, J.A., 213 Akao, A., 231, 438 Akhmetov, A.R., 489 Akimoto, Y., 112 Akinnusi, O.T., 372 Akita, H., 425 Akiti, S., 173 Akiyama, K., 112, 123 Akiyama, T., 32, 274 Alami, M., 247, 349– 350, 365 Albericio, F., 242 Alberico, D., 338 Albert, B.J., 489 Albertshofer, K., 122, 129 Albiniak, P.A., 289 Albrecht, M., 342 Alcaide, B., 40, 224 Alcantara, A.R., 368 Aldegunde, M.J., 401 Aleman, J., 379 Alex, K., 200, 485 Alexakis, A., 25–26, 135 Alexander, L.R., 373 Alexiou, G., 269

Fiesers’ Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 491

492

Author Index

Alfonsi, M., 50 Allan, K.M., 424 Allen, L.J., 400 Alliot, J., 338 Almandros, P., 40 Almaraz, E., 417 Almasi, D., 134 Almassy, A., 149 Almendros, P., 224 Almog, J., 473 Almqvist, F., 231 Alonso, D.A., 14, 379 Alonso, F., 293, 433 Alper, H., 46, 264, 349 Alphonse, F.-A., 70 Alsabeh, P., 433 Altermann, S., 263 Althammer, A., 32, 39, 337, 402 Altman, M.D., 200 Altman, R.A., 186 Alvarez-Bercedo, P., 401 Alvarez-Builla, J., 401 Alvarez-Corral, M., 83 Alvarez-Rodrigo, L., 240 Alza, E., 383 Al-Zoubi, R.M., 11 Amade, P., 478 Amatore, M., 175 Amere, M., 173 Amijs, C.H.M., 222 An, D.K., 200, 306 An, G., 312 An, S.E., 221– 222 An, X.-L., 401 An, Y., 224 Anand, R.V., 452 Ananikov, V.P., 294 Andavan, G.T.S., 42 Anderson, D.R., 400 Anderson, E.D., 270 Andersson, H., 231 Andersson, P.G., 149 Andina, F., 169 Ando, A., 116– 117, 116 Ando, M., 441 Andrade, R.B., 401 Andre, V., 390 Andres, J.M., 135 Andrews, S.P., 46 Andrushko, V., 149

Ang, R., 117 Angell, Y., 177 Angrish, D., 401 Anilkumar, G., 146, 245 Anjaiah, S., 300 Ankner, T., 407 Ansensio, G., 433 Antilla, J.C., 105, 153 Antipin, M.Yu., 294 Antlla, J.C., 23 Antoline, J.E., 202 Antonchick, A.P., 32– 33 Antoniotti, S., 225, 478 Antunes, O.A.C., 264, 317 Anzovino, M.E., 438 Aoki, M., 57 Aoyama, H., 447 Aoyama, N., 13, 130 Aponick, A., 222 Appella, D.H., 262 Arai, K., 19–20 Arai, M.A., 123, 341 Arai, N., 72, 152 Arai, T., 13, 72, 77, 105, 135 Araki, S., 209, 253 Araki, T., 365 Aratake, S., 372, 379, 383 Arcadi, A., 50 Arevalo, M.J., 410 Argade, N.P., 278 Argyrakis, W., 146 Arico, F., 244 Ariger, M.A., 43 Arikan, F., 367 Arimitsu, S., 321 Arimura, Y., 77 Arita, S., 105 Armspach, D., 29 Armstrong, A., 247 Armstrong, D.W., 372 Arndtsen, B.A., 467, 469 Arora, P.S., 401 Arraya´s, R.G., 144, 191 Arrington, A.K., 61 Arseniyadis, S., 400 Arvidsson, P.I., 143 Asahara, H., 84 Asahina, M., 117 Asai, C., 66 Asai, F., 306

Author Index

Asai, H., 73, 197 Asai, T., 17 Asai, Y., 288 Asakura, N., 380 Asan, A., 116 Asao, N., 221 Asaoka, M., 231, 306, 419 Asensio, G., 449 Ashfeld, B.L., 36, 338 Ashizawa, T., 153 Aso, A., 433 Assen, E., 343 Ata, F., 460 Aube, J., 278, 434 Aubert, C., 221 Aubert, V., 162 Auge, J., 253 Aulenta, F., 407 Auner, N., 438 Auof, C., 273, 438 Aureggi, V., 300 Au-Yeung, T.T.-L., 112 Avendano, C., 99 Avenoza, A., 401 Avola, S., 237, 343 Awasaki, M.N., 34 Awen, B.Z.S., 274 Ayad, T., 153 Aydin, J., 316 Aydos, G.L., 400 Aye, Y., 17 Aznar, F., 169, 467 Azuma, K., 72 Azumaya, I., 57 Azzouz, M., 447 Azzouz, R., 459 Ba, L.A., 74 Baag, M.M., 278 Baba, A., 195, 255, 257, 443 Baba, T., 437 Babas III, C.F., 122 Babu, D.C., 261 Babu, S.A., 257 Babushkin, D.E., 349 Baceiredo, A., 369 Bach, T., 75 Backes, M., 57 Ba¨ckvall, J.-E., 225, 244, 312 Bae, H.J., 221– 222

Bae, I., 187 Baek, J.Y., 46, 358 Baeza, A., 454 Bagley, M.C., 443 Baglione, S., 342 Bahrami, K., 244 Bailey, W.F., 310 Bajko, Z., 434 Bajracharya, G.B., 123, 341 Bakale, R.P., 444 Baker, B.A., 367 Balaji, S.V., 469 Balakrishna, M.S., 343 Baldino, S., 467 Ballistreri, F.P., 245 Baltaze, J.-P., 253 Banaag, A.R., 144 Bandini, M., 178 Bando, F., 339 Bando, M., 14 Banﬁeld, S.C., 205 Bang-Andersen, B., 467 Banini, S.R., 61 Bannwarth, W., 72 Banphavichit, V., 1239 Bansal, V., 177 Banwell, M.G., 278 Bao, C.-N., 245 Bao, H., 20 Bao, J., 174 Bao, M., 467 Bao, W., 186 Bar, S., 407 Barabe, F., 231, 433 Barajas, J.G.H., 79 Baran, P.S., 449 Barbas III, C.F., 129, 379 Barbazanges, M., 280, 352 Barbe, G., 451 Barchuk, A., 129, 266 Barder, T.E., 337, 467 Bardin, V.V., 349 Barge, A., 419 Barlan, A.U., 87 Barleunga, L., 467 Barluenga, J., 169, 221, 240, 306, 365 Barman, G., 99 Barnes, C.L., 153 Barnes, D.M., 420 Baro, A., 146

493

494

Author Index

Barral, K., 453 Barratt, M.L., 281 Barrault, J., 264 Barrett, A.G.M., 95 Barrett, F.B., 32 Barriault, L., 221 Barrio, P., 169 Barroso, S., 144 Barry, C.S., 89 Bart, S.C., 266 Barta, K., 149 Bartelson, K., 174 Bartley, J.K., 284 Bartoli, G., 99, 173, 284, 379 Bartoszewicz, A., 10 Baruwati, B., 317 Bashiardes, G., 435 Baskar, B., 221–222 Basle, E., 208 Basset, J.-M., 411 Basset, L., 356 Bataille, C.J.R., 369 Bates, R.W., 413 Batey, R.A., 178, 312 Battace, A., 38 Baucom, K.D., 390 Baudoin, O., 338 Bauer, E.B., 41 Bauer, R.C., 231 Bausch, C.C., 309 Baxter, C.A., 182, 247, 400 Bayardon, J., 149 Beaudegnies, R., 300 Beauﬁs, F., 11 Beaulieu, E.D., 451 Beccalli, E.M., 36 Bechara, W.S., 66 Becht, J.-M., 346, 433 Bedel, O., 310 Bedford, R.B., 316–317 Bee, C., 123 Beeler, A.B., 272 Beer, S., 470 Be´gis, G., 458, 483 Begum, S.A., 234 Behenna, D.C., 306 Behrouz, S., 442 Beifuss, U., 448 Bejot, R., 169, 300 Bekele, T., 173

Beletskaya, I.P., 294, 433 Bell, A.T., 192 Bell, H.P., 337 Bell, M., 173 Bellas, L., 84 Beller, M., 32, 45, 78, 146, 153, 178, 181, 186, 200, 245, 267, 327, 338– 339, 367, 425, 485 Bello, A., 413 Bello, P., 321 Belmont, P., 414 Benagla, M., 17 Benaglia, M., 117, 178, 410 Bencivenni, G., 447 Bender, C.F., 221 Bender, T.P., 264 Benetsky, E.B., 34 Benfatti, F., 469 Beniazza, R., 87 Bentley, J.T., 117 Bentley, P.A., 163 Benz, E., 310 Berard, D., 356 Bergander, K., 302 Bergman, R.G., 47, 410 Berhal, F., 300 Berkaoui, A.-L.B., 244 Berkessel, A., 173, 375 Berlande, M., 122 Berlin, J.M., 400 Berlouis, L.E.A., 78 Berman, A.M., 47 Bernad, P.L., 406 Bernandinelli, G., 61, 135 Bernard, A.M., 302 Bernardi, D., 74 Bernardinelli, G., 144 Berndt, M., 407 Bernier, D., 368 Berrue, F., 478 Berry, J.F., 453 Bertelsen, S., 379 Berthiol, F., 38, 135 Berthod, M., 247 Berthon-Gelloz, G., 360 Bertogg, A., 144 Bertrand, G., 400 Bertrand, M.B., 337 Bertus, P., 239 Best, D., 203

Author Index

Betham, M., 317 Bethuel, Y., 289 Bettinger, H.F., 358 Bezzenine-Lafollee, S., 407 Bhadra, S., 87 Bhalerao, D.S., 263 Bhanage, B.M., 318 Bhanushali, M.J., 318 Bhanthumravin, W., 129 Bhattacharyya, K.X., 213 Bhor, S., 19 Bhowmik, D.R., 261 Bhusan, P.B., 367 Bhuvaneswari, S., 365 Bi, H.-P., 337, 433 Bian, Y., 245 Biannic, B., 222 Bieber, L.W., 483 Biechy, A., 201 Bielawski, M., 163 Bieniek, M., 401 Bienz, S., 144 Bifﬁs, A., 177 Bigdeli, M.A., 437 Bigeault, J., 338 Bignon, J., 350 Bihelovic, F., 434 Bikard, 343 Bill, E., 266 Billingsley, K.L., 337, 467 Binder, C.M., 417 Binder, J.T., 221, 365 Bini, L., 57 Binkley, M.S., 410 Binnemans, K., 264 Biradar, A.V., 245 Birkholz, M.-N., 112 Birman, V.B., 105 Bischoof, L., 459 Biscoe, M.R., 36, 467 Bissember, A.C., 278 Bistri, O., 85, 269 Biswas, D., 281 Biswas, S., 269 Bitterlich, B., 146, 245 Biyikal, M., 310 Bjo¨rklund, M., 231 Bjorsvik, H.-R., 400 Black, D.A., 469 Blake, A.J., 368

Blakey, S.B., 389 Blanc, A., 222 Blanc, F., 411 Blanchard, N., 401 Blanchet, J., 130 Blanco, E.G., 169 Blanco-Urgoiti, J., 64 Blaszykowski, C., 365 Blay, G., 19, 23, 123, 144 Blechert, S., 123, 310, 400 Blond, G., 434 Blum, J., 46, 321 Boas, U.,1 94 Bobbitt, J.M., 310 Bochet, C.G., 297 Boddaert, T., 401 Bode, J.W., 10, 143, 160 Bodor, A., 264 Boebel, T.A., 42 Boeda, F., 400 Boelens, M., 84 Boersma, A.J., 144 Boger, D.L., 269 Bojer, D., 89 Bolig, A.D., 351 Bolm, C., 85, 123, 129, 149, 269, 372 Bolshan, Y., 312 Bolze, P., 379 Bombek, S., 485 Bondarev, O., 34, 380 Bondarev, O.G., 34 Bonge, H.T., 357 Bora, U., 318 Borah, A.J., 187 Borcsek, B., 434 Boren, B.C., 425 Borguet, Y., 196 Borhade, R., 321 Born, R., 401– 402 Bornemann, H., 358 Bo¨rner, A., 78, 112, 149 Borsini, E., 36 Bosch, L., 189 Bosco, M., 173, 284 Bosdet, M.J.D., 365 Boskovic, Z.V., 367 Botta, G., 375 Bottalico, D., 234 Boucau, J., 173 Bougrin, K., 146

495

496

Author Index

Bouhadjera, K., 437 Bour, C., 434 Bournaud, C., 135 Bourque, L.E., 191 Bouwkamp, M.W., 266 Bouziane, A., 461 Bovonsombat, P., 85 Bower, J.F., 96, 266 Bower, J.R.F., 42 Bowers, A.A., 435 Bowman, A.C., 266 Bowornkiengkai, T., 85 Boyd, W.C., 410 Boyer, F.-D., 401 Braga, A., 112 Braga, A.L., 117, 178 Brancour, C., 365 Brandhorst, K., 470 Brasche, G., 178, 312 Bra¨se, S., 300 Braun, H., 300 Breazzano, S.P., 321 Brecker, L., 434 Bredihhin, A., 89 Breit, B., 2, 4, 112 Brelot, L., 324 Brennan, M.K., 112 Brennfu¨hrer, A., 339 Breton, T., 435 Brewer, M., 437 Brinkman, Y., 144 Brinkmann, C., 32 Brioche, J.C.R., 338 Brion, J.-D., 247, 349–350, 365 Britto, S., 301 Broady, S.D., 179 Brodmann, T., 112 Broggini, G., 36 Brookhart, M., 266, 351 Broussons, S., 349 Brown, J.M., 327 Brown, M.K., 112 Brown, N., 467 Brown, S.P., 455 Browne, D.M., 353 Bruckmann, A., 372 Bru¨ckner, R., 72 Bru¨dgam, I., 407 Brummond, K.M., 64 Bruneau, C., 461

Brunel, J.M., 317, 338, 416 Bryman, L.M., 425 Buch, C., 45 Buchmeiser, M.R., 400 Buchotte, M., 153 Buchwald, S.L., 36, 160, 178, 186– 187, 237, 312, 337– 339, 467 Buckle, R.N., 79 Budynina, E.M., 478 Buendia, J., 236, 312 Buevich, A.V., 99 Bull, J.A., 181 Bulut, A., 116 Bunnelle, E.M., 365 Bunuel, E., 296 Buono, G., 338 Buranaprasertsuk, P., 186 Bures, J., 444 Burger, K., 242 Burgers, K., 177 Burguete, M.I., 117 Burk, M.T., 17, 123 Burke, C.P., 146 Burke, N., 318 Burke, S.D., 144, 300 Burks, M.D., 321 Burton, J.W., 287 Busacca, C.A., 149, 401 Busto, J.H., 401 Buszek, K.R., 467 Butler, C.R., 61 Butler, T., 489 Butova, E.D., 203 Bu¨ttner, T., 45 Buzas, A.K., 222, 227 Byrne, C.M., 460 Cabirol, F.L., 453 Cabral, S., 274 Cabrera, S., 144, 379 Cacchi, S., 318, 321 Caddick, S., 291, 390 Caeiro, J., 294 Caﬁero, L.R., 423 Cahiez, G., 235 –236, 312 Cai, C., 208, 318, 346, 411 Cai, P., 310 Caijo, F., 400 Calderisi, M., 300 Calhoun, L.A., 59

Author Index

Callis, N.M., 317 Calvert, G., 401 Cambeiro, X.C., 383 Campagna, M., 144 Campagne, J.-M., 269, 401 Campana, A.G., 419 Campbell, K., 400 Campbell, L., 221 Campbell, M.J., 234, 467 Campeau, L.-C., 338 Campo, M.A., 337 Canales, E., 143– 144, 455 Candito, D., 342 Canesi, S., 356 Cantet, A.-C., 243 Canturk, B., 92 Cao, B., 324 Cao, J., 321 Cao, L., 161, 267 Cao, W., 186 Cao, Y.-J., 383 Capet, M., 349 Capitaa, F., 467 Capretto, D.A., 224 Capriati, V., 91 Carberry, P., 2 Carboni, B., 461 Carcani, L.G., 425 Cardenas, D.J., 296 Cardillo, G., 469 Cardona, F., 473 Cariou, K., 221, 365 Carling, R., 452 Carlone, A., 173, 284, 379 Carmeli, M., 249 Caroosi, L., 25 Carpino, L.A., 203 Carra, R.J., 452 Carraz, C.A., 34 Carreaux, F., 461 Carreira, E.M., 43, 46, 247, 349 Carreras, J., 401 Carrero-Martinez, G., 318 Carret, S., 434 Carretero, J.C., 144, 191, 291 Carril, M., 181, 269 Carroll, M.A., 203 Carroll, P.J., 89, 92, 309 Carson, C.A., 287 Caruana, P.A., 343

Casares, J.A., 310 Casarotto, V., 173 Casey, C.P., 195 Castanet, A.-S., 91 Castanet, Y., 322 Castedo, L., 365, 401– 402 Castet, F., 241 Castillo, D., 162 Castro, J.L., 182 Castroriejo, M.P., 92 Catala, C., 346 Catalano, V.J., 365 Catellani, M., 342 Cattenati, C., 143 Caupene, C., 423 Cecchi, L., 178 Ceclerc, A., 196 Cedilote, M., 2 Celentano, G., 17, 117 Centikaya, B., 322 Cespedes-Guirao, F.J., 257 Cha, J.K., 337, 411 Chabaud, L., 241 Chacko, S., 450 Chacko, S.A., 283 Chai, G., 236 Chai, L., 199 Chakraborti, A.K., 207, 458 Champagne, B., 343 Champagne, T.M., 455 Chan, A., 10 Chan, A.S.C., 112, 144, 153, 327 Chan, C.S., 365 Chan, J., 390 Chan, P.W.H., 186 Chan, S.H., 153 Chan, T.H., 112 Chan, T.-M., 99 Chan, W.-H,. 144 Chand, D.K., 289 Chandler, C.L., 372 Chandrasekhar, S., 367, 383 Chandrashekar, S.P., 117 Chang, C.-C., 419 Chang, H.-T., 176 Chang, J., 269 Chang, J.W.W., 186 Chang, L., 375 Chang, S., 181, 187, 357 Chang, T.-C., 203

497

498

Author Index

Chang, Y., 130 Chankeshwara, S.V., 458 Chapman, R.N., 401 Charette, A.B., 66, 135, 149, 297, 338, 451 Charnay-Pouget, F., 239 Chartrand, A., 101 Charyk, D., 324 Chase, P.A., 78 Chassaing, S., 181, 481 Chatani, N., 7, 73, 96, 197 Chatterjee, S., 196 Chattopadhyay, A., 283 Chattopadhyay, K., 343 Chaturvedi, D., 460 Chatwichien, J., 324 Chaudhari, H.K., 417 Chaudhari, K.H., 263 Chavant, P.Y., 490 Chavasiri, W., 186, 205 Che, C.-M., 39, 213, 221–222, 370 Chebolu, R., 458 Chee, S., 186 Cheekoori, S., 264 Cheemala, M.N., 153 Chein, R.-J., 153 Chelucci, G., 467 Cheminade, X., 8 Chemla, F., 302 Chemler, S.R., 160, 182 Chen, A., 328 Chen, B., 373 Chen, C., 117, 157, 296, 356 Chen, C.-A., 21– 22 Chen, C.-F., 482 Chen, C.-H., 287 Chen, C.-W., 236 Chen, C.-Y., 231, 439 Chen, D., 64, 257 Chen, D.X., 414 Chen, D.Y.-K., 271 Chen, F.-E., 356 Chen, F.-X., 117 Chen, G.-Y., 144 Chen, H., 383 Chen, H.-F., 338 Chen, H.-H., 186 Chen, H.Y., 375 Chen, J., 47, 50, 225, 322, 338, 483 Chen, J.-H., 346 Chen, J.-R., 123, 401

Chen, K., 375, 449 Chen, L., 123, 467 Chen, M., 179, 294, 346, 426 Chen, M.-J., 237 Chen, P.W.H., 261 Chen, S., 85, 257 Chen, S.-K., 117 Chen, S.-N., 343 Chen, S.-Y., 23 Chen, T., 17, 247 Chen, W., 187, 237 Chen, W.-F., 439 Chen, X., 123, 289 Chen, X.-H., 33 Chen, Y., 50, 101, 143, 179, 224, 356, 467 Chen, Y.-C., 130 Chen, Y.-J., 186 Chen, Z., 17, 224 Chen, Z.-B., 458 Chen, Z.-C., 117 Chen, Z.-F., 321 Chen, Z.-X., 253 Chenel, C., 454 Cheng, C., 318 Cheng, C.-H., 57, 166, 176, 295, 365 Cheng, D., 357 Cheng, H.M., 411 Cheng, H.-Y., 38 Cheng, J., 322, 324, 433, 467 Cheng, J.-P., 123, 382– 383 Cheng, K., 402 Cheng, L., 383 Cheng, S.-T., 365 Cheng, T.-M., 3 Cheng, X., 434 Cheng, Y., 21, 316, 321 Cheong, H.-L., 253 Cheong, J.Y., 221–222 Cheong, P.H.-Y., 63, 129 Cherney, R.J., 341 Chernyak, N., 338, 349 Cheruku, P., 149 Cherukupally, P., 483 Chesnokov, A.A., 368 Chethan, N., 469 Cheung, H.Y., 112, 187 Chevallier, F., 281, 309 Chi, D.Y., 101, 439 Chi, K.-W., 421 Chi, Y., 373, 379

Author Index

Chi, Y.S., 210 Chiacchio, U., 402 Chianese, A.R., 67 Chiang, P.-C., 160 Chiang, W., 318 Chiarini, M., 50 Chiaroni, A., 263 Chiba, K., 208 Chiba, N., 231, 306 Chiba, S., 8, 390 Chida, N., 467 Chidambaram, M., 352 Chien, H.-L., 87 Chien, S.-C., 318 Chin, J., 23 Chirik, P.J., 266 Chisholm, J.D., 2, 458 Chitimalla, S.K., 203 Chlenov, A., 400 Cho, C.-W., 59 Cho, E.J., 401, 462 Cho, J., 42 Cho, K., 123 Cho, M., 313 Cho, S.-D., 467 Cho, S.H., 181, 187, 357 Cho, W.K., 210, 224 Choi, A., 186 Choi, H., 187 Choi, I.S., 210, 224 Choi, L.B., 2 Choi, S.Y., 46, 174, 213, 389 Choi, T.J., 358 Choi, W., 194 Choi, Y.M., 200 Chollet, G., 144 Chong, J.M., 19, 467 Chopade, P.R., 57 Chotana, G.A., 51 Chou, H.-H., 144 Choudary, B.M., 343 Chowdhury, N., 257 Chowdhury, R.R., 236 Choy, J.M.L., 261 Christensen, J.B., 194 Christoforou, A., 358 Christy, J.P., 295 Chrovian, C.C., 57 Chu, C.-M., 99 Chu, Q., 208, 380

Chua, G.-L., 264 Chuang, D.-W., 21 Chuman, H., 199 Chun, K.-S., 312 Chung, M.-W., 349 Chung, W.-J., 17 Chung, Y.K., 46, 174, 213, 389, 412, 434 Chuprakov, S., 166, 349, 458 Church, T.L., 460 Churchill, G.H., 247 Chuzel, O., 123 Ciufolini, M.A., 356 Cladingboel, D.E., 458, 483 Clark, D.A., 400 Clark, J.R., 400 Clark, J.S., 182 Clark, T.P., 339 Clarke, A.J., 400 Clarkson, G.J., 458 Clary, J.W., 200 Clave, G., 123 Clavier, H., 400 Clayden, J., 91 Cleary, P.A., 191 Cleary, T.P., 2 Clift, M.D., 99 Clive, D.L.J., 194 Cloke, F.G.N., 390 Clososki, G.C., 285 Coates, G.W., 425, 460 Coelho, A.V., 317 Coggan, J.A., 264 Colacot, T.J., 349 Colbourne, J.M., 410 Colby, D.A., 269 Coldham, I., 90 Coleman, M.G., 389 Colin, J., 17 Collado, M., 117 Colladon, M., 245 Collet, F., 157 Colletti, S.L., 221 Collin, J., 406 Collins, J., 411 Coltart, D.M., 284 Comasseto, J.V., 101, 302 Company, A., 270, 287 Concellon, C., 406, 417 Concellon, J.M., 169, 285, 403, 406, 417 Connon, S.J., 173

499

500

Author Index

Conrad, J., 448 Consorti, C.S., 400 Constantinescu, M., 389 Cook, G.R., 19, 75, 257 Cook, M.J., 105 Cooper, D.J., 314 Cooper, G., 400 Coperet, C., 411 Coquerel, Y., 400–401 Cordonnier, M.-C., 222 Cordova, A., 10, 373, 379– 380 Corey, E.J., 85, 143– 144, 153, 306, 423, 460, 475 Corma, A., 210–211, 224 Correa, A., 269 Correa, W., 153 Cortez, G.A., 400 Cortez, N.A., 152 Coseri, S., 417 Cossı´o, F.P., 144 Cossy, J., 87, 236, 280, 352, 400 Costas, M., 270, 287 Coste, A., 253 Cote, A., 135 Cotte, A., 181 Counts, W.R., 48 Courillon, C., 447 Couty, F., 280 Couty, S., 87, 352 Cowen, B.J., 143 Cozzi, F., 410 Cramer, N., 28 Crane, A.K., 236 Cravotto, G., 419 Creech, G.S., 444 Crich, D., 435 Crimmin, M.R., 95 Crone, B., 221, 262, 365 Crooks, P.A., 421 Cross, C.M., 467 Cruces, J., 84 Cruz, A.C.F., 338 Cruz, M., 410 Cryddenb, C.M., 59 Csajagi, C., 434 Csaky, A.G., 59– 60 Csekei, M., 346 Cu, X., 321 Cuadro, A.M., 401 Cuenca, A., 187 Cuerva, J.M., 419, 441

Cui, H.-F., 135, 191 Cui, Q., 7 Cui, S.-L., 187, 458 Cui, X., 321, 375 Cun, L.-F., 22, 375 Cunha, R.L.O.R., 302 Curran, D.P., 208, 380 Cutarelli, T.D., 280 Cutting, G.A., 130 Cvengros, J., 34 Cychosz, K.A., 327 Czako, B., 407 Dahl, T., 467 Dai, L.-X., 10, 26, 152 Dai, X., 47, 68, 296 Dai, Y., 149 Daini, M., 5 Dake, G.R., 365 Dalpozzo, R., 284 Damodar, K., 257 Dang, J., 130 Dang, Y., 179 Danheiser, R.L., 346 Daniel, A., 96 Darses, S., 47, 71 Darvas, F., 434 Darwish, A., 467 Das, B., 99, 257, 261, 367 Das, K., 191 Das, P., 305 da Silva, R.A., 483 Dastbaravardeh, N., 294 Datta, A., 456 Datta, S., 222 Dauban, P., 157 Daugulis, O., 187, 328 Davankov, V.A., 34, 112 Dave, A.H., 123 Davi, M., 455 David, O., 280 Davies, H.M., 144 Davies, H.M.L., 389, 412 Davies, I., 416 Davies, I.W., 231, 349, 442 Davies, P.W., 365 Davoli, P., 84 Day, B.W., 74 De, A., 91 De, R.L., 343

Author Index

de Almeida, L.S., 450 DeAngelis, A., 389 de Arellano, C.R., 433 de Azeredo, J.B., 178 DeBerg, J.R., 489 Debieux, C., 73 Debleds, O., 401 De Bo, G., 360 DeBoef, B., 48, 324 de Cuba, K.R., 32 Deﬁeber, C., 43 Deiters, A., 162 De Jesus, M., 153 Dekhane, D.V., 321 De Kimpe, N., 84, 231 De la Campa, R., 306 de la Cruz, W., 153 de la Herran, G., 60 de las Infantas, M.J.P., 242 Delaude, L., 196 de la Zerda, J., 352 del Campo, T.M., 40, 224 del Carmen Hita, M., 17 Delfosse, S., 196 de Lima, P.G., 264, 317 del Pozo, C., 208, 321, 401 Dembinski, R., 438 De Meijere, A., 488 Demerseman, B., 461 Demir, A.S., 370 Demir, S., 322 Demizu, Y., 105 Demonceau, A., 196 Denes, F., 11, 302 Deng, C.-L., 177, 191, 321 Deng, G., 187, 191, 339 Deng, G.-J., 67, 411 Deng, H., 312, 365 Deng, J., 149, 153, 337 Deng, L., 173– 174 Deng, L.-J., 346 Deng, Q.-H., 39 Deng, R., 296 Deng, Y., 350, 425 den Hartog, T., 135 Denmark, S.E., 17, 38, 61, 123, 198 Denolf, B., 231 Deobald, A.M., 178 de Oliveira Santos, J.S., 423 de Pomar, J.J., 79

Deport, C., 153 Derane, D., 470 Deria, P., 89 Derien, S., 162 de Riggi, I., 338 Derrick, A., 66 Derridj, F., 38 Desai, L.V., 356 De Sarlo, F., 178 Deschamp, J., 123 Deschenes-Simard, B., 454 Desmarets, C., 343 de Souza, A.L.F., 317 de Souza, R.O.M.A., 242 Despotopoulou, C., 231 Desrosiers, J.-N., 66, 149 Deutsch, D., 367 Devine, P.N., 416 Devine, S.K.J., 469 Devlin, A.S., 389 De Vos, D.E., 264 de Vries, A.H.M., 149 de Vries, J.G., 130, 149, 186 Dhal, R., 437 Dhimane, A.-L., 221, 365 Dhond, P.K., 2 d’Hondt, S., 490 D’hooghe, M., 84 Dhoro, F., 144 Di, J., 403 Diaconescu, P.L., 317 Di Antonio, G., 99 Diaz, M.R., 417 Diaz, P., 285 Di Bari, L., 23 Dickstein, J.S., 341 DiCunto, P., 91 Dieguez, A., 221 Dieguez, M., 149, 160 Dieguez-Vazquez, A., 269 Diesen, J.S., 149 Dieskau, A., 424 Dietrich, H., 153 Diez-Gonzalez, S., 10, 455 Dilger, A.K., 144, 300 Diner, P., 379 Ding, J., 322, 467 Ding, K., 20, 85, 373 Ding, P., 213 Ding, Q., 415

501

502

Author Index

Ding, X., 116– 117 Ding, Z., 129 DiPasquale, A.G., 455 Disadee, W., 143 Diver, S.T., 400 Dixneuf, P.H., 162 Dixon, D.D., 417 Dixon, D.J., 221 Djebbar, S., 38 Do, H.-Q., 187 Docherty, G., 247 Docherty, P.H., 287 Dodd, R.H., 157 Dodda, R., 375 Dogan, O., 116–117 Dogo-Isonagie, C., 173 Dohi, T., 163, 353, 356, 452, 454 Dohlnahl, M., 310 Doi, T, 96 Dolman, S.J., 442 Dominbgo, L.R., 123 Dominguez, E., 181, 353 Dominguez, G., 64 Donahue, J.P., 225 Donati, N., 266 Dong, H., 389, 484 Dong, J., 372 Dong, K.-Y., 135 Dong, S., 375 Dong, V.M., 157, 356 Dong, X-Q., 135 Dong, Z., 144 Dongare, M.K., 245 Donohoe, T.J., 247, 369 Dore, D.D., 117 Doriguetto, A.C., 248 Dormer, P.G., 231 Dorta, R., 14 Dossetter, A.G., 182 Dou, Q., 18 Dou, Y., 202 Doucet, H., 38, 389 Doug, V.M., 339 Douglas, C.J., 400 Doyle, A., 438 Doyle, A.G., 108 Doyle, M.P., 87, 385, 485 Draghici, C., 437 Dresner, K.N., 456 Driega, A.B., 478

Driver, T.G., 105, 389, 484 Drouin, M., 411 Du, D.-M., 32 Du, H., 20, 28, 181, 187, 434 Du, J., 163 Du, X, 372 Du, Y., 269 Duan, H., 40 Duan, H.-F., 117 Duan, S., 169 Duan, W., 382 Duan, W.-L., 28 Duan, X.-H., 337, 433 Duan, Z., 316, 321 Duan, Z.-C., 149, 337 Duarte, M.T., 390 Dubey, A.K., 283 Dubey, D.K., 368 DuBois, J., 389 Dubovyk, I., 38, 343 Dubrovina, N.V., 112 Ducki, S., 91 Dudding, T., 173 Dudley, G.B., 211, 289 Dudnik, A.S., 221, 224, 259, 349 Duesler, E., 379 Du¨fert, A., 300 Duffy, L.A., 407 Dufour, J., 91 Dufour, S., 401 Duhayon, C., 17 Dujardin, G., 437 Dumas, A.S., 324 Dunach, E., 8 Dunet, G., 482 Dunet, J., 87 Dunetz, J.R., 346 Dunstan, T.A., 200 Duplais, C., 312 Duplasi, C., 235– 236 Duplessis, M., 231, 433 Dupont, J., 400 Dupruis, L., 343 Durbin, M.J., 61 Durham, A., 483 Du¨rner, G., 144 Duschek, A., 221– 222 Dussault, P.H., 314 Dutheuil, G., 306

Author Index

Dwight, T.A., 324 Dzhemilov, U.M., 489 Eagon, S., 153 Ebata, S., 57 Ebeling, G., 400 Eberhardt, L., 29 Ebran, J.-P., 349 Echavarren, A.M., 222, 412, 419 Echevarria, A., 479 Edmonds, D.J., 71 Edney, D.D., 67 Edwards, A.S., 101 Edwards, D.R., 59 Egami, H., 146 Egi, M., 222 Ehrmantraut, J., 173 Eichhorn, T., 129 Eidam, H.S., 338 Eidam, P., 338 Einhorn, C., 105 Einhorn, J., 105 Eisenberger, P., 452 Ejiri, S., 40 Ekoue-Kovi, K., 86 Ekstro¨m, J., 152 El Abed, D., 273, 438 Elamparuthi, E., 99 El Bialy, S.A.A., 300 Elemes, Y., 358 El Hajjaj, S., 26 El Kaim, L., 325 El Kazzi, A., 369 Ellman, J.A., 47, 86, 129–130 Elmore, S., 269 Elmorsy, S.S., 483 Elsevier, C.J., 342 Elsner, P., 379 Enache, D.I., 284 Enders, D., 10 Endo, K., 51, 259 –260, 318 Endo, M., 321 Endo, Y., 77, 123 Engel, D.A., 211 Engers, D.W., 83 England, D.B., 83 English, E.P., 373 Engman, M., 149 Engquist, P.-A., 321 Enoki, Y., 66

Enthaler, S., 78, 153, 267 Epperson, M.T., 452 Er, Y.Q., 261 Erre, G., 78, 267 Ertelt, M., 424 Escorihuela, J., 117 Espinet, P., 310 Espinosa, A., 242 Esquivias, J., 144, 191 Esser, B., 263 Estevam, I.H.S., 483 Esteves, P.M., 450 Estevez, R.E., 441 Ethirajan, M., 337 Evangelisti, C., 210 Evans, D.A., 17, 423 Evans, P., 273 Evans, W.J., 455 Fabrizi, G., 318, 321 Faghihi, M.A., 442 Fagnou, K., 321, 338, 341 Failes, T., 266 Falciola, C.A., 25, 135 Falck, J.R., 169, 173, 300 Fall, Y., 38, 257 Fan, G.-F., 117 Fan, Q., 153 Fan, Q.-H., 67 Fan, R., 356–357 Fananas, F.J., 92, 221, 240 Fandrick, D.R., 10, 112 Fang, F., 284 Fang, G.Y., 90 Fang, L., 303 Fang, Y., 186 Fang, Y.-Q., 144, 337 Fang, Z., 24, 312, 346 Farina, V., 401 Faulo, H., 169 Favre-Reguillon, A., 247 Faye, D., 437 Faza, O.N., 187 Feldman, K.S., 187, 280 Felpin, F.-X., 356 Feltenberger, J.B., 269 Feng, C.-G., 47 Feng, J., 22, 327 Feng, J.-J., 490 Feng, L., 174

503

504

Author Index

Feng, X., 19, 22, 117, 123, 129, 144, 173, 257, 375, 454 Feng, X.-M., 117 Feng, Z., 157 Fensterbank, L., 221, 365 Ferber, B., 117 Ferderigos, N., 269 Feringa, B.L., 23, 25, 135, 144 Fernandez, A., 221 Fernandez, B., 321 Fernandez, I., 19, 23, 146, 321 Fernandez, M., 368 Fernandez, R., 153 Fernandez, Y., 92 Fernandez-Ibanez, M.A., 23 Fernandez-Lazaro, F., 257 Fernandez-Rodriguez, M.A., 221 Fernandez-Suarez, M., 204 Ferraris, D., 129 Ferreira, F.P., 83 Ferreira, L.C., 242 Fesard, T.C., 46, 349 Fiandanese, V., 234 Fiedler, P., 57 Field, L.D., 266 Fiethaus, M., 358 Filimonov, V.D., 417, 421 Fillion, E., 434 Findik, H., 370 Fiorante, P.F., 83 Fioravanti, S., 359 Firmansjah, L., 467 Firouzabadi, H., 460 Fischer, D.F., 155 Fisher, E.L., 92 Fisher, G.B., 200 Flanigan, D.L., 389 Fleet, G.W.J., 203 Fleming, F.F., 486 Fleming, M.J., 281 Fleming, W.S., 373 Floreancig, P.E., 196 Florez, J., 169, 306 Florio, S., 91 Flowers II, R.A., 99 Flynn, B.L., 262 Fokim, V.V., 187 Fokin, A.A., 203 Fokin, V.V., 425 Font, D., 15

Font-Sanchis, E., 257 Fontaine, P., 263 Fontrodona, X., 287 Fordyce, E.A.F., 294 Foreancig, P.E., 490 Formentin, P., 400 Fors, B.P., 36 Forsyth, C.J., 211 Fort, Y., 343 Forte, G., 318 Fortner, K.C., 123 Foster, B.S., 416 Foubelo, F., 25, 275, 280 Foucoin, F., 423 Fowler, C., 236 Fox, J.M., 198, 389 Fox, M.E., 149 Foxman, B.M., 174 Francais, A., 310 France, S., 173 Francioo, G., 149 Franck, X., 123 Frank, D., 488 Frankowski, K.J., 453 Frantz, D.E., 231 Frater, G., 193 Fraunhoffer, K.J., 327 Friestad, G.K., 201, 346 Fro¨hlich, R., 89, 302, 310 Frohn, H.-J., 349 Fro¨lander, A., 153 Frongia, A., 302 Frontier, A.J., 92, 144, 266, 343, 385, 410 Frost, C.G., 71, 291 Fruit, C., 459 Fu, C., 162 Fu, G.C., 108, 144, 157, 296, 467 Fu, H., 19, 179, 375 Fu, P., 129 Fu, Y., 129, 187, 321, 346 Fuchibe, K., 32, 274 Fuentes, B., 310 Fuentes, N., 419 Fugami, K., 321 Fujie, T., 204 Fujihara, T., 469 Fujii, E., 354 Fujii, N., 38, 187, 211, 338, 433– 434 Fujii, S., 337 Fujii, T., 204

Author Index

Fujimoto, H., 173 Fujimoto, J., 77 Fujimoto, T., 84 Fujino, K., 135 Fujioka, H., 99, 354 Fujioka, S., 135 Fujita, D., 84 Fujita, K., 66, 266 Fujita, M., 129 Fujiwara, H., 390, 437 Fujiwara, T., 101, 278 Fukiwara, N., 222 Fukuda, T., 112 Fukudome, Y., 187 Fukumoto, K., 77 Fukumoto, Y., 73, 197 Fukushima, H., 101 Fukushima, K., 278 Fukuyama, T., 96, 112, 204, 221, 402, 460 Fukuzawa, S., 144, 410 Fuller, P.H., 182 Fu¨lo¨p, F., 117 Funabiki, K., 380 Funami, H., 365 Funasaka, S., 14, 380 Funasaki, N., 420 Funatomi, T., 438 Funk, T.W., 400 Furman, B., 45 Fu¨rstner, A., 47, 188, 273, 365 Furukawa, N., 291 Furukawa, T., 173 Furuta, A., 247 Furuta, T., 337, 467 Furuyama, T., 309 Fushimi, M., 143 Fustero, S., 321, 401 Futamura, Y., 89 Gabriele, B., 350 Gaddam, V., 272 Gade, L.H., 176 Gagliardo, M., 316 Gagne, M.R., 67, 221 Gagnon, A., 231, 433 Gagosz, F., 222, 227 Gaillard, S., 197, 365 Gaillard, T., 338 Galan, B.R., 400 Galetto, F.Z., 112

Galliford, C.V., 278 Gallo, M.A., 242 Gallon, B.J., 317 Gallou, F., 448 Galzerano, P., 284 Gamba-Sanchez, D., 243 Gamez-Montano, R., 326 Ganci, G.R., 2 Gandon, V., 221 Ganesan, K., 195 Ganesh, K.R., 186 Ganguly, T., 91 Gao, J., 45, 146, 369, 407 Gao, J.-X., 152 Gao, L., 467 Gao, M., 261 Gao, S., 99 Gao, W., 434 Gao, Y., 149 Garcia, D., 275 Garcia, H., 210–211 Garcia-Bosch, I., 287 Garcia-Delgado, N., 459 Garcia-Egido, E., 204 Garcia-Fandino, R., 401 Garcia-Fortanet, J., 312 Garcia-Garcia, P., 221, 379 Garcia-Garcia, S., 417 Garcia-Granda, S., 306 Garcia-Iglesias, M., 296 Garcia-Munoz, S., 83 Garcia-Yebra, C., 222 Garner, G., 200 Garner, L., 401 Garnier, J.-M., 239 Garrett, M.R., 123 Gaspar, B., 247 Gaspari, M., 205, 475 Gatti, M., 14 Gattrelle, W., 369 Gau, H.-M., 21– 22 Gaul, M.D., 244 Gaulon, C., 437 Gaunt, M.J., 379 Gavrilov, K.N., 34, 112 Gavryushin, A., 294 Gawin, R., 400 Gayduk, K.A., 294 Ge, F., 283 Ge, H., 324

505

506

Author Index

Ge, Y., 368 Ge, Z.-M., 3 Gealageas, R., 213 Gebbink, R.J.M.K., 316 Gelalcha, F.G., 146, 245 Gellman, S.H., 373, 379 Gelman, D., 467 Gelman, S.H., 7 Gembus, V., 442 Genesio, E., 360 Genet, J.-P., 47, 71, 152–153, 221, 225, 402 Genin, E., 225 Gennari, C., 4, 135 Gentilucci, L., 469 Georg, G.I., 324 Gerla, K., 400 Gesson, J.-P., 243 Gevorgyan, V., 166, 221, 224, 259, 338, 349, 458 Ghelﬁ, F., 312 Ghiron, C., 360 Ghorai, M.K., 191 Ghorai, S., 400 Ghosh, H., 356 Ghosh, P., 302 Ghosh, S.K., 269 Giacomina, F., 149 Gibbs, S.A., 434 Gil, R., 406 Gilbertson, S.R., 48 Gilley, C.B., 297 Gillingham, D.G., 112 Gilmkhanova, M.P., 245 Gilmore, C.D., 424 Gimbert, Y., 338 Gimeno, N., 400 Gin, D.Y., 452 Gini, F., 135 Giofre, S.V., 402 Giordano, L., 338 Giorgi, M., 273, 438 Giovannini, R., 99 Girard, D., 349 Giraud, A., 247 Giri, R., 321, 328 Giroux, S., 401 Giudici, R.E., 5, 400 Giuli, S., 99 Gladiali, S., 78 Gleason, B.L., 434

Gleave, R., 71 Gleiter, R., 263 Glinton, K., 450 Glossop, P.A., 369 Gnanadesikan, V., 130 Go¨bel, M.W., 144 Goble, S.D., 64 Goddard, R., 273, 380 Goddard-Borger, E.D., 251 Godet, T., 414 Godineau, E., 241 Goeke, A., 193, 208 Goggiamani, A., 321 Gogoi, P., 368 Gogsig, T.M., 349, 467 Goh, P.J., 261 Gohier, F., 437 Gohil, S., 149 Gois, P.M.P., 3980 Goldberg, D.P., 245 Goldberg, S.D., 400 Golden, K.C., 259 Golden, M.D., 179 Gomez, C., 406 Gomez, E., 410 Gomez, L., 270 Gomez-Bengoa, E., 173, 380, 419 Gomez-Gallego, M., 321 Gong, J., 485 Gong, L.-Z., 22, 32– 33, 122, 173, 375 Gonnade, R.G., 166 Gonzales-Gomez, J.C., 25 Gonzalez, A.Z., 455 Gonzalez, I., 84 Gonzalez-Arellano, C., 211 Gonzalez-Nunez, M.E., 449 Gonzalez-Rodriguez, C., 462 Goodby, J.W., 349 Goodenough, K.M., 338 Goossen, L.J., 179, 187, 191, 339 Gopalarathnam, A., 26, 112 Gopalsamuthiram, V., 144, 300 Gopinath, C.S., 349 Goralski, C.T., 200 Gorelsky, S.I., 338 Gorin, D.J., 221 Gornitzka, H., 369 Gosmini, C., 175 Goti, A., 473 Goto, A., 51, 356, 454

Author Index

Goto, T., 108 Goto, Y., 173 Gotoh, H., 379– 380, 447 Gotor, V., 83 Gottumukkala, A.L., 38 Gou, F.-R., 433 Gou, H.-M., 21 Gou, S., 22, 117, 173 Gouault, N., 208 Goudreau, S.R., 297 Goushi, S., 380 Gowrisankar, S., 328 Grachan, M.L., 123 Gracia-Delgado, N., 129 Graham, A.E., 259 Grainger, D.M., 91 Grandmarre, A., 471 Granja, J.R., 401 Grant, T.N., 414 Grasa, G.A., 349 Gray, K.C., 321 Greaney, M.F., 101, 247, 349, 447 Grecian, S., 278, 434 Greco, G.E., 434 Green, M.E., 490 Green, M.J., 339 Greene, A.E., 338 Gregg, B.T., 259 Grela, K., 400–401 Greshock, T.J., 460 Gribkov, D.V., 321 Gridnev, L.D., 130 Griesbeck, A.G., 313 Grigg, R., 66 Grimaud, L., 326 Grinberg, N., 149 Grise, C., 1 Grise, C.M., 221 Grishin, Y.K., 478 Grossman, O., 467 Groth, U.M., 89 Grotjahn, D.B., 461 Grove, J., 84 Grubbs, R.H., 400 Grunenberg, J., 470 Gru´tzmacher, H., 266 Gru¨tzmacher, H.-G., 45 Gu, X., 18 Gu, Y., 32, 264 Guadagnin, R.C., 83

Guadarrama-Morales, O., 201 Guan, B., 312 Guan, B.-T., 237, 269 Guan, H., 195 Guan, J.T., 349 Guarna, A., 281 Gu¨ell, M., 270 Guerinot, A., 236 Guibe, F., 407 Guillarme, S., 23 Guillena, G., 17, 372 Guillerez, M.-G., 144 Guillot, R., 17, 99 Guin, D., 317 Guixa, M., 173 Guizzetti, S., 17, 117 Gulias, M., 365 Gun’ko, Y., 173 Guo, C., 32, 173 Guo, C.-C., 257 Guo, H., 116, 146 Guo, L., 379 Guo, L.N., 337, 433 Guo, M., 294 Guo, Q., 32, 310 Guo, Q.-X., 22, 32, 187, 321 Guo, S., 224 Guo, S.-M., 191, 321 Guo, X., 161, 389 Guo, X.-X., 135 Guo, Y.-W., 444 Gupta, A.K., 368 Gupta, P.K.,195 Gurjar, M.K., 196 Gustafson, J.L., 461 Guzei, I.A., 341 Guzman, I., 153 Ha, D.G., 11 Haak, E., 84, 454 Habaue, S., 312 Habiak, V., 235 Habibi, Z., 411 Habrant, D., 89 Hachisu, S., 201 Haddad, N., 149 Haddenham, D., 153, 200 Hadei, N., 237, 343 Haga, T., 135 Hagiwara, H., 61, 274

507

508

Author Index

Hahn, F.E., 10 Hajra, S., 407 Halder, R., 379 Haleema, S., 79 Halim, R., 262 Hall, A., 187 Hall, D.G., 25 Halliburton, L.M., 306 Hallonet, A., 253 Ham, J., 92 Ham, S., 23 Hama, T., 61 Hamada, T., 129, 312 Hamada, Y., 38, 112 Hamaguchi, H., 434 Hamashima, Y., 68, 108 Hamid, M.H.S.A., 64 Hammann, J.M., 324 Hammerer, T., 123 Hammond, G.B., 321, 423 Hamse, A., 247 Hamura, T., 300 Hamza, K., 46 Hamze, A., 350, 365 Han, C., 486 Han, H., 26, 357 Han, J., 10, 305 Han, J.H., 253 Han, S.B., 123 Han, W., 321 Han, Z., 401 Hanada, S., 247 Hanan, J., 23 Handa, S., 123, 130 Haneda, S., 312 Hanefeld, U., 453 Hanessian, S., 401, 454 Hanna, I., 401 Hannedouche, J., 123 Hansen, A.L., 349 Hansen, J.S., 194 Hansen, T., 357 Hanzawa, Y., 10, 60, 351 Hao, J., 283 Hao, M.-H., 401 Hara, H., 71 Hara, K., 296 Hara, O., 38 Harada, S., 255, 341, 410, 452 Harada, T., 21, 278

Hardin, A.R., 366 Hare, A., 240 Harel, T., 249 Harmer, J., 266 Harmer, M.A., 425 Harrak, Y., 365 Harris, J.R., 105 Harrison, T.J., 365 Harrity, J.P.A., 234, 338 Hart, D.J., 248 Hartel, A.M., 306 Hartikka, A., 143 Hartl, H., 407 Hartley, B.C., 291 Hartwig, J.F., 20, 26, 38, 42, 51, 57, 59, 61, 112, 192, 421, 443 Harumashi, T., 51 Harutunyan, S.R., 135 Hasegawa, Y., 10 Hashimoto, A., 278, 337 Hashimoto, M., 460 Hashimoto, R., 289 Hashimoto, S., 283 Hashimoto, T., 18, 22, 157 Hashimoto, Y., 302 Hashizume, D., 68 Hassan, A., 123 Hassan, A.E.A., 416 Hasuoka, A., 407 Hata, K., 354 Hata, M., 420 Hata, S., 146 Hata, T., 187 Hatakeyama, T., 231, 259 Hatano, K., 380 Hatano, M., 17, 117, 418 Hatori, Y., 354 Hattori, G., 390 Haudrechy, A., 310 Haug, T.T., 221 Ha¨ussinger, D., 372 Hauwert, P., 342 Hayama, M., 166 Hayase, S., 338, 460 Hayash, Y., 6 Hayashi, A., 253 Hayashi, M., 312 Hayashi, N., 195, 257, 443 Hayashi, R., 75, 257 Hayashi, S., 57, 199, 337

Author Index

Hayashi, T., 5, 13, 28, 47, 49– 50, 70–71, 144, 235– 236, 360 Hayashi, Y., 372, 379– 380, 383 Hayes, D., 306 Hazell, R.G., 379 He, A., 169 He, C., 224, 426 He, H., 26, 144 He, J., 305 He, J.-Q., 483 He, L., 143, 357, 375 He, M., 143 He, S., 382 He, W., 266 He, W., 92 He, Y., 305, 425 He, Y.-M., 67 He, Z., 36 Headley, A.D., 382– 383 Hearn, M.T., 11 Heckenroth, M., 342 Heemstra Jr, J.R., 17, 123 Heilmann, E.K., 365 Helgert, T.R., 42 Heliou, M., 461 Helliwell, M., 91 Hellkamp, S., 337 Helquist, P., 406 Henderson, A.P., 23 Henderson, J.L., 101 Hengst, C., 175 Henry, C., 208 Henry, C.E., 444 Henze, M., 410 Hepp, A., 89 Herath, A., 57 Hernandez-Olmos, V., 123 Herndon, J.W., 169, 352 Herold, M., 338 Herrero, M.T., 353 Herzon, S.B., 421 Hess, W., 175 Hessen, B., 135 Hester, D.K., II, 187 Heumann, L.V., 21 Heydari, A., 194 Hey-Hawkins, E., 34 Hicks, J.D., 448 Higashi, K., 360 Higashi, M., 89

Higashibeppu, Y., 402 Higham, R., 203 Hili, R., 253 Hill, M.D., 452 Hill, M.S., 95 Hilmersson, G., 407 Hilt, G., 175 Hinago, T., 306 Hinata, Y., 57 Hintermann, L., 192 Hirai, A., 434 Hirakawa, H., 288 Hirakawa, T., 338 Hirama, M., 406 Hirano, K., 57, 337–338 Hirano, M., 59–60, 71, 391 Hirao, T., 245 Hirashita, T., 209, 253 Hirata, M., 407 Hirata, N., 105, 116 Hirato, Y., 57 Hirobe, M., 199 Hiroi, K., 242 Hirokama, Y., 155, 443 Hirokawa, Y., 195 Hirose, H., 99 Hirose, M., 18 Hirose, R., 283 Hirose, T., 46 Hitce, J., 338 Hitchcock, S.R., 117 Hiyama, T., 47, 50, 57, 89 Hleba, Y.B., 59 Ho, C.M., 414 Ho, C.-Y., 57 Ho, T.-L., 101 Hock, A.S., 411 Hodgson, D.M., 281, 401 Hodgson, R., 7 Hoerter, J.M., 7 Hofmeister, A., 488 Holla, H., 367 Hollander, L.B., 434 Hollis, T.K., 42 Holz, J., 112, 149 Holzapfel, C.W., 339 Home, W.S., 373 Hon, X., 484 Hon, Y.-S., 338 Honda, H., 257

509

510

Author Index

Hong, B.-C., 379 Hong, D., 458 Hong, J., 194 Hong, J.-B., 108 Hong, L., 117 Hong, M.S., 105 Hong, S.H., 400 Hong, Y.-T., 59 Hooper, A.M., 401 Hopkins, E.A., 373 Horai, M., 354 Hori, K., 59 Horie, S., 354 Horiguchi, H., 338 Horiike, M., 366 Horino, Y., 339 Horisaki, K., 89 Horita, A., 50 Horn, J., 72 Horvath, I.T., 264 Horzella, M., 123 Hoshi, M., 79 Hoshi, T., 61, 274 Hoshino, T., 420 Hosokawa, T., 270 Hosomi, A., 253, 366 Hossein, M.D., 261 Hotha, S., 210 Hotz, J., 78 Hou, D.-R., 38, 349 Hou, X.-L., 28, 112, 152 Hou, Z., 19, 375 Houk, K.N., 63, 129 Houpis, I.N., 237 Ho¨velmann, C.H., 324 Hoveyda, A.H., 5, 112, 129, 400 Howard, B.E., 415 Howard, J.A.K., 23 Howell, A.R., 400 Hreczycho, G., 85, 95 Hrib, C.G.,470 Hsieh, H.-P., 203 Hsieh, I.-L., 439 Hsieh, Y.-D., 349 Hsu, C.-M., 321 Hsu, M.-H., 321 Hsu, Y.-C., 222 Hsung, R.P., 202, 269 Hu, B., 289 Hu, C., 123

Hu, H., 244, 248 Hu, H.-P., 149 Hu, J., 32, 306, 337 Hu, L., 274, 368 Hu, P., 269 Hu, Q., 7 Hu, W., 32, 389, 414 Hu, X., 173, 194 Hu, X.-C., 321 Hu, X.-P., 337 Hu, Y., 318, 346 Hu, Z.-K., 130 Hua, M.-Q., 77, 191 Hua, R., 57, 257, 349 Huang, C.-T., 375 Huang, F., 64, 178 Huang, G., 179 Huang, H., 32, 389 Huang, J., 92, 123, 129, 144, 169, 202, 266, 372 Huang, J.-D., 149, 337 Huang, J.-M., 253, 255 Huang, J.-Q., 346 Huang, J.-S., 213 Huang, K., 153 Huang, K.-T., 204 Huang, L.-F., 236 Huang, L.-N., 117 Huang, P.-Q., 231 Huang, Q., 337 Huang, W., 269, 403, 413 Huang, W.-J., 287 Huang, X., 123, 173, 197, 211, 227, 365, 441 Huang, X.-C., 101 Huang, Y., 263, 375 Huang, Z., 79, 309, 416 Huard, K., 389 Hubbard, A., 453 Huber, J.D., 129, 400 Hudlicky, T., 205, 411 Huffman, M.A., 349, 442 Hughes, A., 416 Hughes, D.L., 1 Hughes, T.S., 418 Huguenot, F., 253 Huh, C.W., 448 Hui, H., 179 Hui, X.-P., 117 Hulcoop, D.G., 287 Hulin, B., 274 Humphrey, C., 416

Author Index

Hus, S., 261 Hussain, S.M.S., 23 Hutchings, G.J., 284 Hutchings, M.G., 181 Hutson, G.E., 123 Hwang, G.-S., 7 Hwang, H.Y., 421 Hwang, I.-C., 221 Hwang, J.-H., 221 Hwang, J.P., 244 Hyde, A.M., 467 Hyder, Z., 337 Hyeon, T., 87 Hyett, D.J., 34 Hyodo, T., 234 Iada, A., 35 Iannazzo, D., 402 Ibarra-Rivera, T., 326 Ibdah, A., 337 Ibnusaud, I., 79 Ibragimov, A.G., 489 Ibrahem, I., 373 Ibrahem, I., 379–380 Ichikawa, J., 84, 207, 253, 366 Ichikawa, Y., 47, 50, 192 Idonets, P.A., 433 Ieawsuwan, W., 32, 236 Ienco, A., 162 Igarashi, D., 153 Igarashi, E., 488 Igarashi, T., 117 Igawa, K., 314 Iglesias, M., 211 Ihara, M., 434 Iida, S., 199 Iijima, D., 274 Iizuka, M., 291, 321 Ikariya, T., 105, 130, 444 Ikawa, T., 317, 467 Ikeda, D., 235, 338 Ikeda, H., 57 Ikeno, T., 411, 413 Ilardi, E.A., 262 Imagawa, H., 288, 410 Imahori, H., 288 Imahori, T., 401 Imai, M., 129, 166 Imamoto, T., 153 Imao, D., 166

511

Imaoka, D., 278 Inahashi, N., 101 Indada, Y., 48 Innitrizer, A., 434 Inokuchi, E., 38 Inomata, K., 123 Inoue, G., 366 Inoue, M., 406 Inoue, T., 72 Inoue, Y., 346 Inui, M., 407 Ionescu, D., 203 Ipner, G., 45 Ipposhi, J., 360 Iranpoor, N., 460 Irle, S., 51 Isambert, N., 410 Isart, C., 444 Ischay, M.A., 191 Ishibashi, H., 93, 447 Ishida, K., 365 Ishida, N., 469 Ishida, T., 247 Ishida, Y., 426 Ishifune, M., 283 Ishihara, K., 11, 17, 117, 143, 201, 351, 380, 418, 434, 437 Ishii, T., 135 Ishii, Y., 43, 460 Ishikawa, H., 269, 354, 379–380 Ishikawa, K., 166 Ishikawa, S., 237 Ishikawa, T., 135, 143 Ishikura, M., 1 Ishino, T., 379 Ishiyama, T., 51 Iskra, J., 261 Islam, A., 261 Ismail, M.A., 483 Isobe, M., 192, 318 Istrate, F.M., 222, 227 Itami, K., 63 Ito, F., 434 Ito, H., 112, 227 Ito, M., 105, 353 Ito, S., 112, 231 Ito, Y., 166, 434, 442 Itoh, A., 313 Itoh, F., 484 Itoh, J., 32

512

Author Index

Itoh, T., 173, 338, 372, 379, 460 Itoh, Y., 260 Iuchi, M., 338 Iuliano, A., 375 Ivanov, D., 389 Ivanova, O.A., 478 Iwabuchi, Y., 435 Iwai, M., 410 Iwai, T., 469 Iwamoto, H., 478 Iwanami, K., 247 Iwasaki, M., 306, 337 Iwasawa, N., 57, 291, 365, 471 Iwasawa, T., 341, 469 Iwata, M., 353 Iwata, S., 300 Iyer, K., 439 Izgu¨, E.C., 116 Izumi, A., 43 Izumi, S., 57 Jackson, M., 149 Jackson, S.K., 478 Jackstell, R., 45 Jacobsen, E.N., 108 117, 123, 129, 144 Jacquesy, J.-C., 356 Jahnke, M.C., 10 Jaipetch, T., 484 Jalalian, N., 163 Jamison, T.-F., 57, 406 Jammi, S., 187 Jana, U., 269 Jang, D.O., 205, 253 Jang, H.-Y., 108 Jang, K.P., 389 Jang, Y., 87 Jasra, R.V., 454 Jatsch, A., 424 Jautze, S., 155 Javaherian, M., 442 Jayanth, T.T., 57, 176 Jayaprakash, D., 22 Jazzar, R., 144 Jean, A., 356 Jean, M., 208, 349 Jeanneau, E., 281, 309 Jee, N., 485 Jeganmohan, M., 166, 365 Jenkinson, S.F., 203

Jenks, W.J., 337 Jennings, M.P., 234 Jensen, K.L., 467 Jensen, T., 467 Jensen, V.R., 400 Jeon, H.B., 358 Jeon, I., 85 Jeon, S.I., 92 Jeon, S.-J., 92 Jeong, B.-S., 173, 373 Jeong, H.-J., 101 Jeong, M., 293,467 Jereb, M., 261 Jerome, F., 264 Jerome, L., 458, 483 Jew, S., 373 Jew, S.-S., 173 Jeyakumar, K., 289 Jheengut, V., 372 Ji, A., 201 Ji, K.-G., 419 Ji, S.-J., 66 Jia, A., 403 Jia, W., 328 Jia, X., 303, 407 Jia, Y., 61 Jia, Y.-X., 32 Jiang, B., 202, 372 Jiang, C., 385 Jiang, D., 19, 89, 467 Jiang, H., 105, 326, 379 Jiang, H.-F., 346 Jiang, H.-Y., 224 Jiang, J., 32, 173, 375 Jiang, J.-J., 17 Jiang, J.-X., 257 Jiang, M., 7 Jiang, T., 346 Jiang, W., 379 Jiang, X.Z., 187 Jiang, Y., 19, 179, 375 Jiang, Y.-Q., 14 Jiang, Y.-Z., 375 Jiao, J., 99 Jiao, L., 63– 64, 356 Jiao, N., 328 Jiao, P., 24 Jida, M., 99 Jimenez, D., 401 Jimenez, L.S., 87

Author Index

Jimenez, T., 441 Jimenez-Gonzalez, L., 83 Jimeno, C., 383 Jin, C., 410 Jin, C.H., 417 Jin, C.K., 489 Jin, M., 382 Jin, M.-J., 117 Jin, T., 225 Jin, Y., 312, 372 Jin, Z.-L., 321 Jing, T.-T., 116 Jin, T., 453 Joensuu, P.M., 174, 294 Joh, D.Y., 425 Johansen, M.B., 478 Johansen, R.L., 379 Johansson, M., 244 John, M.P., 130 John, O.R.S., 442 Johns, A.M., 38 Johnson, J.S., 123, 234, 309, 467 Johnson, M.J.A., 401 Johnston, J.N., 130, 447 Jones, K.L., 187 Jones, P.G., 470 Joo, T.Y., 205 Jordaan, M., 400 Jordan, J.P., 400 Jorgensen, K.A., 173, 379 Jorgensen, M., 467 Joseph, B., 261 Josselyn, R., 324 Jothilingam, S., 208 Jou, D.-G., 101 Jouannetaud, M.-P., 243, 356 Joyce, L.A., 373 Ju, J., 293, 467 Jun, B.-H., 322 Jun, C.-H., 47 Jun, Y.M., 253 Jung, B., 105 Jung, H.M., 293, 467 Jung, K.W., 321, 389 Jung, P., 7 Jung, P.M.J., 300 Jung, Y.H., 417 Junge, K., 78, 153, 267, 367 Junk, C.P., 425 Jurberg, I.D., 222

Jurca, T., 78 Jutand, A., 433 Kabro, A.A., 34 Kaburagi, Y., 289 Kadam, S.T., 391 Kadoh, Y., 433 Kadowaki, S., 227, 247 Kaeobamrung, J., 160 Kafka, S., 201 Kagan, H.B., 117 Kagawa, N., 467 Kaide, T., 328 Kailas, T., 122 Kairimi, A., 244 Kaiser, H.M., 178, 425 Kajihara, Y., 309 Kajimoto, T., 262 Kakei, H., 143 Kakiguchi, K., 452 Kakiuchi, F., 96 Kakiuchi, K., 375, 438 Kalbarczyk, K.P., 400 Kalesse, M., 123 Kalinin, V.N., 34 Kalita, H.R., 187 Kallepali, V.A., 51 Kaltenbach III, R.F., 341 Kalyani, D., 40 Kamal, A., 417 Kamata, T., 306 Kamath, S.S., 105 Kambe, N., 234, 237, 434 Kamijo, S., 453 Kamimura, A., 264 Kamisawa, A., 59 Kamiya, M., 423 Kammerer, C., 338 Kampf, J.W., 401 Kamps, I., 89 Kan, T., 337, 467 Kanai, M., 130, 134, 144, 189 Kaname, M., 402 Kanan, M.W., 312, 450 Kananovich, D.G., 239 Kanchiku, S., 143 Kandur, W.V., 349 Kaneaki, T., 199 Kaneko, M., 57, 257 Kaner, R.B., 317

513

514

Author Index

Kang, D.H., 205 Kang, E.J., 67 Kang, E.S., 291 Kang, H., 92, 322 Kang, J.-E., 221 Kang, Q., 32 Kang, S.H., 105 Kang, S.M., 210, 224 Kang, T.-R., 130 Kang, Y.K., 89 Kangani, C.O., 74 Kanger, T., 122, 135 Kanno, A., 60 Kanno, K.-I., 488 Kano, T., 22, 77 Kansui, H., 253 Kantam, M.L., 343 Kantchev, B., 343 Kanyiva, K.S., 57 Kappe, C.O., 433, 469 Kar, A., 178, 425 Karadeolian, A., 478 Karam, A., 264 Kargbo, R., 19 Karnik, A.V., 105 Karshtedt, D., 192 Kashimura, S., 283 Kashiwabara, M., 149 Kataerva, O., 231 Kataoka, H., 278 Katayama, T., 321 Kato, F., 242 Kato, K., 14, 380, 425 Kato, T., 369 Katoh, T., 71, 135, 262, 316 Katsukawa, M., 351 Katsuki, T., 143, 146 Kattnig, E., 273 Katzenellenbogen, J.A., 439 Kawabata, T., 201, 281 Kawagoe, S., 66 Kawaguchi, H., 416 Kawaguchi, Y., 440 Kawahara, N., 166 Kawahata, M., 135, 278 Kawai, D., 209 Kawai, H., 93, 346 Kawai, M., 274 Kawai, N., 135 Kawakami, S., 281

Kawakami, Y., 123 Kawamoto, T., 40 Kawamura, T., 423 Kawamura, Y., 270 Kawasaki, M., 178, 438 Kawasaki, T., 117 Kawasaki-Taksuka, T., 231 Kawashima, T., 306 Kawata, A., 259 Kawatsura, M., 241, 338, 460 Kawauchi, S., 135 Kayakawa, I., 99 Kayaki, Y., 105, 444 Kazemi, F., 442 Kazmaier, U., 445 Ke, J.K., 261 Keck, G.E., 21 Keep, A., 66 Kein, H., 45 Keister, J.B., 400 Kelleher, S., 273 Keller, A.I., 208 Keller, M., 4 Kelley, D.E., 74 Kemmitt, P.D., 287 Kempe, R., 46 Kenmoku, S., 306 Kennedy, A., 7 Kennedy, A.R., 452 Kerber, W.D., 245 Kerr, M.A., 287, 478 Kerr, W.J., 306 Kesavan, S., 272 Kessabi, J., 300 Khaksar, S., 194 Khaladkar, T.P., 196 Khalaﬁ-Nezhad, A., 442 Khalil, A.-G.M., 483 Khamooshi, F., 411 Khan, H.A., 157 Khan, N.H., 454 Khiar, N., 146 Khodaei, M.M., 244 Khokhlow, A.R., 34 Khorshidi, A., 402 Khurana, J.M., 283 Ki, Z., 454 Kiariya, T., 105 Kiau, S., 341 Kidwai, M., 177

Author Index

Kieltsch, I., 452 Kienle, M., 146 Kier, M.J., 434 Kigoshi, H., 99 Kii, S., 231 Kikuchi, M., 231 Kikuchi, S., 410 Kikuchi, T., 51 Kikugawa, Y., 353 Kikushima, K., 245 Killeen, N.M., 443 Kim, A., 221 Kim, B.H., 253 Kim, B.M., 194 Kim, C.H., 389 Kim, D., 194 Kim, D.W., 101 Kim, G., 7 Kim, H., 64, 108, 194, 253, 486 Kim, H.J., 439 Kim, H.-K., 467 Kim, H.-M., 174 Kim, I.S., 42, 67, 417 Kim, J., 87, 153 Kim, J.G., 21, 253 Kim, J.-H., 322 Kim, J.-J., 467 Kim, J.M., 328 Kim, J.N., 328 Kim, J.S., 253 Kim, J.Y., 187 Kim, K.H., 328 Kim, K.M., 23 Kim, K.S., 358 Kim, K.W., 194 Kim, M.J., 194 Kim, M.M., 349 Kim, M.-R., 467 Kim, M.S., 200 Kim, S., 194, 208, 253 Kim, S.-H., 187, 291 Kim, S.-J., 373 Kim, S.K., 357 Kim, S.M., 174, 213 Kim, S.S., 391, 454 Kim, S.Y., 46, 174 Kim, T., 467 Kim, T.H., 328 Kim, T.W., 105 Kim, Y.H., 244

515

Kimura, M., 112, 339 Kimura, T., 407 Kinemuchi, H., 312 Kingston, J.V., 337 Kinoshita, A., 288 Kinoshita, T., 117 Kipke, A., 316 Kiran, S., 198 Kiraz, C.I.A., 87 Kirosawa, H., 438 Kirsch, G., 74 Kirsch, S.F., 15, 221– 222, 262, 365 Kirschning, A., 245, 353 Kishi, Y., 289 Kita, T., 105, 116 Kita, Y., 99, 163, 353–354, 356, 454, 484 Kitagaki, S., 379 Kitahara, F., 453 Kitahara, K., 460 Kitahara, T., 43 Kitajima, M., 354 Kitamura, M., 77, 155 Kitamura, T., 261, 366 Kitamura, Y., 318, 337, 467 Kitano, C., 278 Kitano, Y., 208 Kitawaki, T., 467 Kitazaki, E., 452 Kitazume, T., 310 Kiyono, Y., 454 Kiyooka, S., 43, 68 Kiyotsuka, Y., 234, 310 Klaiber, I., 448 Klasek, A., 201 Klein, A., 473 Kleiner, C.M., 285 Kloesges, J., 369 Kloetzing, R.J., 231 Klosin, J., 149 Klumpp, D.A., 450 Kluser, E., 342 Knapp-Reed, B., 57 Knight, D.W., 284 Knochel, P., 83, 153, 231, 285, 294, 309, 328, 417, 482 Knowles, D.A., 443 Knyazeva, I., 349 Ko, B., 470 Ko, C., 269 Kobayashi, C., 105

516

Author Index

Kobayashi, H., 312 Kobayashi, K., 38, 40, 441 Kobayashi, S., 19– 20, 129, 135, 258, 270, 407 Kobayashi, Y., 234, 297, 309– 310, 318, 343, 483 Kocevar, M., 485 Kociok-Ko¨hn, G., 130 Ko¨ckritz, A., 32 Kocovsky, P., 149 Koenig, S.G., 444 Koga, Y., 296 Koide, A., 153 Koide, K., 401, 489 Koike, T., 105 Koizumi, T., 84 Koizumi, Y., 186 Kojima, M., 68 Kojima, R.W., 317 Kokubo, M., 407 Kolinin, V.N., 34 Kollarovic, A., 57 Koloda, D., 401 Koltunov, K.Yu., 6 Kolundzic, F., 240 Komagawa, S., 57 Komano, K., 406 Komatsu, Y., 338 Komeyama, K., 75, 269 Konakahara, T., 181 Kondo, S., 146 Kondo, T., 192 Kondo, Y., 34, 160, 291, 309, 321, 341, 433 –434 Kondoh, A., 187 Kong, J.R., 59 Kong, L., 28, 149 Kongkathip, B., 269 Kongkathip, N., 269 Ko¨nig, B., 488 Ko¨nigsmann, M., 266 Konishi, H., 258 Konishi, K., 262 Konishi, T., 369 Konta, S., 255 Konwar, D., 368 Kopf, N.A., 379 Koranne, P.S., 341 Korapala, C.S., 201 Korboukh, I., 193 Korivi, R.P., 295 Kormas, C.M., 316 Korthals, K.A., 169

Kosaka, S., 434 Koschek, K., 410 Koseki, Y., 135 Koshizawa, T., 38 Kosmrlj, J., 201 Kostin, G.A., 349 Kosugi, M., 321 Kosugi, Y., 201, 380 Kotani, M., 437 Kotbagi, T.V., 245 Kotov, V., 324 Kotschy, A., 346 Kotsuki, H., 135, 192 Kouklovsky, C., 401 Kouznetsov, V.V., 79 Kovics, I., 434 Kowase, S., 321 Koyuncu, H., 117 Kozak, C.M., 236 Kozak, J.A., 365, 486 Kozaki, T., 318 Kozlowski, M.C., 341 Kozuka, S., 43 Kragol, G., 231 Kramer, J.W., 425, 460 Kramer, R., 72 Krasnokutskaya, E.A., 417, 421 Krasovskiy, A., 231, 271 Kraus, G.A., 85 Krause, H., 274 Krause, N., 367 Krausova, Z., 57 Kress, M.H., 231 Kreutter, K.D., 244 Kribber, T., 192 Kriis, K., 122, 135 Krische, M.J., 41– 42, 59, 67, 96, 123, 129, 266 Krishna, P.R., 257 Krishnaiah, M., 99, 257, 261 Krishnamurthi, J., 247 Kristensen, T.E., 144 Krivoshey, A., 349 Krompiec, S., 197 Krumlinde, P., 225 Krustalev, V.N., 294 Ku, J.-M., 173 Ku, S.-Y., 48, 186 Kuang, L., 85, 373 Kubo, E., 84 Kubo, O., 452

Author Index

Kuchenbeiser, G.R., 42 Kudirka, R., 469 Kudo, D., 317 Kudo, T., 207 Kuenkel, A., 32, 75 Kuhakarn, C., 83, 484 Ku¨hn, F.E., 245 Kuil, M., 29 Kulinkovich, O.G., 239 Kulkarni, S.J., 244 Kumadake, I., 166 Kumadaki, I., 116– 117, 166 Kumamoto, T., 135 Kumar, A., 177, 191 Kumar, D.N., 105 Kumar, P., 402, 416 Kumar, R., 207 Kumar, S., 402, 416 Kumarraja, M., 181, 481 Kume, A., 317 Kummeter, M., 42 Kunai, A., 101 Kundaikar, H.S., 417 Ku¨ndig, E.P., 61, 144 Kunieda, T., 253 Kunimatsu, S., 255 Kunimune, I., 38 Kuninobu, Y., 40, 84, 259, 385 Kuniyasu, H., 234, 237, 339, 434 Kuo, C.-W., 99 Kuo, Y.-H., 318 Kurach, P., 89 Kureshy, R.I., 454 Kuriaki, I., 452 Kurita, J., 433 Kurita, T., 312, 318 Kuriyama, M., 38, 105, 375 Kuriyama, W., 153 Kurono, N., 72 Kurosawa, H., 57 Kusakabe, T., 425 Kusama, H., 365, 471 Kusano, H., 38, 149 Kutateladze, A.G., 306 Kuwahara, R., 284 Kuwajiri, K., 201 Kuwano, R., 4, 38, 149 Kuwata, Y., 71 Kuznik, N., 197 Kwon, C.H., 306

Kwon, O., 444, 458 Kwong, F.Y., 112, 144, 187 Kwong, P., 236 Kyne, R.E., 353 Laali, K.K., 453 Laars, M., 122, 135 Labeeuw, O., 402 Labonne, A., 192 Lacey, J.R., 270 Lacoste, E., 122 Ladepeche, A., 379 Lafrance, M., 321, 338 Lai, G.-Q., 257 Lai, K.-M., 327 Lai, R.-Y., 247 Lai, Y.-Y., 383 Lai, Z.-C., 482 Lalic, G., 423 Lalli, C., 281 LaLonde, A.D., 343, 349 LaLonde, R.L., 67 Lam, F.L., 112, 153 Lam, H.W., 174, 294 Lam, K.H., 153 Lambert, J., 343 Lambshead, K., 71 Lamont, S.G., 247 Lan, J., 22 Lan, Y., 346 Lanari, S., 99 Landa, A., 379 Landais, Y., 87, 122, 241 Lang, A., 467 Langford, S.J., 11 Langiotz, B.K., 176 Lantos, D., 264 Lanza, T., 447 Larhed, M., 321 Larionov, O.V., 460, 475 Larivee, A., 338 Larmanjat, B., 280 Larock, R.C., 61, 101, 328, 337, 423 Larrosa, I., 328 Larsen, C.R., 461 Larson, C.H., 187 Larsson, A., 401 Laschat, S., 146 Lasne, M.-C., 130, 173 Laso, A., 123

517

518

Author Index

Lassaletta, J.M., 153 Lata, C.J., 59 Lattanzi, A., 375 Lau, J.-J., 129 Lauher, J., 406 Laureano, H., 253 Laurent, I., 400 Lautens, M., 2, 160, 284, 289, 337–338 Lavallo, V., 400 Lavilla, R., 410 Lawrence, J.F., 423 Lazareva, A., 328 Le, T., 400 Leadbeater, N.E., 316 Leardini, R., 447 Lebedev, O., 439 Lebel, H., 19, 321, 389, 455 Le Bras, J., 317 Lebrasseur, N., 328 Lecornue´, F., 239 Lectard, S., 191 Lectka, T., 173 Le Drian, C., 346, 433 Leduc, A.B., 478 Lee, A., 23 Lee, A.W.M., 144 Lee, B.M., 253 Lee, B.S., 101, 439 Lee, C., 50, 64 Lee, C.-L., 247 Lee, C.-T., 149 Lee, D., 149, 401, 462 Lee, D.-H., 117, 322 Lee, E., 389 Lee, E.C., 157 Lee, E.E., 160 Lee, E.-S., 221 Lee, H., 149, 194, 448 Lee, H.G., 411 Lee, H.-S., 210, 224, 328 Lee, H.W., 144 Lee, H.Y., 417 Lee, J.-E., 181, 221, 328 Lee, J.H., 221 Lee, J.J., 253 Lee, J.-K., 210, 224, 467 Lee, J.M., 357 Lee, K., 244, 253, 373 Lee, K.Y., 328 Lee, P.H., 253, 469, 486

Lee, S., 92, 134, 293 Lee, S.H., 417 Lee, S.I., 7, 46, 174, 434 Lee, S.J., 67, 321 Lee, S.-S., 287 Lee, Y., 112 Lee, Y.-J., 482 Lee, Y.-S., 322 Lee, Y.T., 412 Lefort, L., 149 Le Gall, E., 483 Leger, J.-M., 435 Legg, A.D., 448 Legouin, B., 211 Legrave, G., 253 Lehmann, C.W., 273 Lehmann, F., 247 Lei, A., 294, 312, 346, 426 Leighton, J.L., 129, 400 Leisch, H., 205 Leitch, D.C., 440, 486 Leitner, A., 26 Leitner, W., 149 Leleti, R.R., 289 Lemaire, M., 247 Lemhadri, M., 38 Lemiere, G., 221 Lennon, I.C., 149 Leogane, O., 321 Leonard, J., 179 Lerebours, R., 344 Leseurre, L., 221 Leslie, B.E., 389 Lesme, G., 143 Letko, C.S., 42 Letourneux, Y., 416 Lettan II, R.B., 278 Leubbers, T., 294 Levacher, V., 442 Levy, L.M., 187, 337, 339 Lewis, A.K.deK., 291 Lewis, J.C., 47, 86 Lex, J., 173 Ley, S.V., 269 Leykajarakul, J., 85 L’Helgonal’ch, J.-M., 281, 309 Li, A., 71 Li, B., 257, 324, 346, 375 Li, B.-J., 324 Li, C., 83, 186

Author Index

Li, C.-F., 401 Li, C.-J., 87, 179, 225, 267, 327, 411 Li, C.-Y., 222 Li, D., 7, 284 Li, D.R., 173 Li, G., 14, 153, 202, 227, 365 Li, G.-Q., 10 Li, H., 161, 174, 186, 309, 312, 373, 379, 382 Li, J., 162, 187, 245., 257, 321, 350, 357, 367, 382, 403, 407, 434 Li, J.-H., 101, 177, 191, 321 Li, J.-J., 321 Li, L., 123, 310, 338 Li, M., 338 Li, M.-B., 74 Li, P., 34, 193, 379, 382 Li, Q., 149, 454 Li, R., 269 Li, R.-T., 3 Li, S., 321, 328, 407 Li, T., 316 Li, W., 57, 152 Li, X., 28, 72, 105, 129, 149, 152, 225, 353 Li, X.-J., 77, 135 Li, Y., 10, 26, 67, 157, 174, 193, 211, 221, 224, 264, 346, 349, 356, 485 Li, Y.-J., 383 Li, Y.-M., 153 Li, Y-X., 144 Li, Y.-Y., 152 Li, Y.-Z., 324 Li, Z., 75, 149, 161, 173, 224, 267, 296, 321, 365, 373 Li, Z.-B., 23 Liang, C., 157 Liang, H., 356 Liang, M., 149 Liang, X., 312, 379 Liang, Y., 32, 64, 101, 153, 356 Liang, Y.-M., 337, 383, 419, 433 Liao, B.-S., 419 Liao, C.-C., 203 Liao, J.-H., 379 Liao, X, 51, 57 Lichtor, P.A., 186–187 Licini, G., 245 Lie, A., 40 Liebert, C., 221, 365 Liebeskind, L.S., 178, 188 Lim, A.E.C., 453

Lim, C., 221 Lim, D., 284 Lim, M., 312 Lim, S.T., 101 Lin, B.-N., 237 Lin, C.-C., 222 Lin, F., 357 Lin, G.-Q., 47, 86, 253 Lin, G.-Y., 221 Lin, H., 445 Lin, J., 173 Lin, K.-W., 439 Lin, S.-H., 365 Lin, W., 153 Lin, Y., 321 Lin, Y.-M., 173 Linares-Palomino, P.J., 450 Linden, A., 14, 173 Linder, C., 187, 339 Lindh, J., 321 Lindhardt, A.T., 349, 467 Lindsay, V.N.G., 135 Lindsay-Scott, P.J., 369 Ling, T., 368 Lingam, Y., 261 Linker, T., 99 Lipshutz, B.H., 149, 177, 349, 367, 400, 489 Liron, F., 328 List, B., 2, 72, 129, 153, 173, 358, 372 –373, 379 Littke, A., 341 Little, K., 231 Liu, B., 157, 237, 318 Liu, C., 321, 426, 478 Liu, C.-R., 74 Liu, C.-Y., 83 Liu, D., 38, 112, 144, 152 Liu, D.R., 312, 450 Liu, F., 174, 187, 255, 380 Liu, G., 7, 68, 327, 400 Liu, H., 32 Liu, J., 123, 152, 224, 306, 318, 338, 346 Liu, J.-L., 22 Liu, J.-T., 99, 375 Liu, K., 135, 372 Liu, L., 57, 101, 187, 196, 321 Liu, M., 253, 322 Liu, P., 63 Liu, Q., 40, 270, 328 Liu, Q.-Z., 22

519

520

Author Index

Liu, R., 312 Liu, R.-S., 198, 221– 222, 365 Liu, S., 18, 57, 123, 146, 152, 178, 188 Liu, S.-T., 237, 247, 419 Liu, S.H., 349 Liu, T.-C., 203 Liu, T.-D., 23 Liu, W., 312 Liu, W.-J., 32 Liu, X., 19, 22, 117, 123, 129, 173, 350, 375, 380, 403, 454 Liu, X.-G., 17, 247, 444 Liu, X.-P., 123 Liu, X.-Y., 213, 221, 337, 419, 433 Liu, Y., 174, 186, 224–225, 278, 310, 346, 380, 419, 485 Liu, Y.-K., 130 Liu, Y.-L., 101 Liu, Z., 38, 59, 61, 101, 144, 328, 337, 423 Liu, Z.-K., 117 Liu, Z.-Q., 199 Livinghouse, T., 486 Liz, R., 83 Llavona, R., 285 Llilst, B., 33 Lliu, W.-B., 26 Lloyd-Jones, G.C., 19 Llyubimov, S.E., 34 Lo, V.K.-Y., 370 Lo, W.F., 178 Lo, W.H., 153 Lobkovsky, E., 266 Lobkovsky, E.B., 425 Locatelli, M., 379 Loefﬂer, J.-P., 343 Loh, J.K., 261 Loh, T.-P., 66, 253, 255 Lohier, J.-F., 423 Lo¨hnwitz, K., 310 Lok, M., 284 Loncle, C., 416 Lopes, D., 447 Lopez, C.S., 187 Lopez, F., 365 Lopez, L.A., 169, 365 Lopez, R., 173 Lopez, S.S., 211 Lopez-Alberca, M.P., 321 Lopez-Carrillo, V., 222 Lopp, M., 122

Lorenz, J.C., 149 Loris, A., 244 Loska, R., 99 Lotesta, S.D., 302 Lou, S., 19, 129 Louie, J., 57 Love, J.A., 423 Lovell, K.M., 456 Lovely, C.J., 144 Lower, A., 489 Lowery, T.A., 434 Lu, B., 162 Lu, C., 99 Lu, G., 130 Lu, J., 356 Lu, J.-M., 278 Lu, M., 440 Lu, P., 46 Lu, S., 467 Lu, W., 269 Lu, X., 68, 174, 231 Lu, Y., 467 Lu, Z., 143, 236 Lu, Z.-L., 144 Luan, X., 14 Lubin-Germain, N., 2 Lucarini, M., 241 Lucarini, S., 20 Luh, T.-Y., 236 Luiken, S., 353 Luis, J.G., 99 Luis, J.M., 270 Luis, S.V., 117 Luisi, R., 91 Lujan, C., 181 Lu¨ken, C., 360 Lulinski, S., 89 Lumby, R.J.R., 174 Lung, C.-Y., 365 Lunn, M., 284 Luo, G., 382 Luo, H., 199 Luo, H.-C., 253 Luo, M., 322 Luo, S., 123, 382 –383 Luo, S.-P., 135, 383 Luo, S.-W., 22 Luo, T., 221, 485 Luo, X., 40 Luo, Z.-B., 22, 152

Author Index

Luparia, M., 144 Lupton, D.W., 130 Lush, S.-F., 198 Lustinec, D., 57 Lutz, F., 117 Luzung, M.R., 143 Lv, G., 467 Lv, X., 186 Lyapkalo, I.M., 453 Lyaskovskyy, V., 302 Lynikate, B., 34 Lyons, T.W., 327 Lyubimov, S.E., 34, 112 Lyubov, D., 17 Ma, A., 379 Ma, D., 129, 186, 379 Ma, G., 380 Ma, H., 312 Ma, H.C., 187 Ma, J.-A., 77, 135, 191 Ma, K., 191 Ma, L., 356 Ma, R., 423 Ma, S., 46, 162, 236, 278, 310, 350, 434 Ma, Y., 425 Macherla, V.R., 368 Machetti, F., 178 Machioka, K., 32 Machotta, A.B., 68 Macia, B., 23 Macina, A., 95 MacMillan, D.W.C., 108, 134 Macnaughton, M.L., 401 MacNeil, S.L., 264 MacPherson, D., 231 Madalska, M., 95 Madec, D., 338, 467 Madhavendra, S.S., 343 Madhavi, P.P., 367 Madhushaw, R.J., 144 Madsen, R., 467 Madu, C.E., 144 Maeda, H., 68, 434 Maeda, L., 105 Maegawa, T., 312, 317– 318 Maehara, A., 324 Maekawa, H., 283 Ma¨eorg, U., 89, 439 Maerten, E., 322, 379

Maestri, G., 342 Maezaki, N., 155 Magens, S., 424 Ma¨gerlein, W., 186, 338 Maggi, R., 413 Magnier-Bouvier, C., 406– 407 Magolan, J., 287 Magriz, A., 153 Mague, J.T., 343 Maguel, N., 160 Magull, J., 488 Mahajan, U.S., 263 Mahdavinia, G.H., 437 Mahesh, M., 78, 452 Mahmood, A., 306 Mahmoodi, N.O., 402 Mahmoud, B., 84 Mahrwald, R., 21 Mai, E., 105, 259 Maio, W.A., 357 Maisonneuve, V., 437 Maiti, S., 269 Maitro, G., 467 Mai, W., 467 Majcher, M., 99 Majetich, G., 84 Majhi, A., 391 Maji, B., 407 Maji, M.S., 310 Majima, K., 273 Majireck, M.M., 193 Mak, S., 186 Makal, A., 400 Maki, B.E., 10 Maki, T., 11 Makino, K., 38 Makosza, M., 99, 368 Maksimova, M.G., 34, 112 Malacria, M., 221, 365, 447 Malanga, C., 300 Malecki, J.G., 197 Maleczka, R.E., Jr., 51 Malerich, J.P., 467 Malkov, A.V., 149 Mallouk, S., 146 Malona, J.A., 410 Malyshev, D.A., 458 Mamaghani, M., 402 Mampreian, D.M., 200 Manabe, K., 237

521

522

Author Index

Manabe, S., 442 Manam, R.R., 368 Mancheno, M.J., 321 Mancheno, O.G., 85 Mancuso, R., 350 Mandal, P.K., 318 Mandal, S.K., 99, 441 Mangelinckx, S., 231 Mangle, M., 186 Mangu, N., 425 Mannam, S., 87 Manolikakes, G., 294 Manorama, S.V., 317 Manral, L., 195 Mansour, E.M.E., 203 Mansueto, R., 91 Mantel, M.L.H., 349 Manzano, R., 135 Mao, S., 64 Marc, S., 162 Marcantoni, E., 99 Marchal, E., 211 Marchese, G., 234 Marciniec, B., 85, 95 Marcuccio, S.M., 433 Marek, I., 302 Margaros, I., 313 Mariampillai, B., 338 Marigo, M., 379 Marimoto, H., 130 Marinelli, F., 50 Marion, N., 10, 213 Marion, O., 11 Mariz, R., 14 Markandeya, N., 417 Marko, I.E., 360 Marks, T.J., 272 Marque, S., 269 Marques, H., 101 Marques, M.M.B., 129 Marras, F., 78 Marrero, J.G., 99 Marrot, J., 243, 280 Marsais, F., 442, 459 Marsden, S.P., 280 Marshall, J.A., 338 Martin, B., 300 Martin, L., 318 Martin, R., 187, 237, 273, 338 Martı´n-Matute, B., 144

Martin-Mingot, A., 356 Martinelli, J.R., 339 Martinez, F., 368 Martinez, P.D.G., 423 Martinez, R., 47, 71 Martinez, S., 318 Martinez-Terrer, J., 449 Marukawa, M., 42 Maruoka, K., 3, 18, 22, 77, 157, 259 Maruyama, A., 163, 356, 454 Marx, A., 410 Mascarenas, J.L., 365 Mase, T., 178, 231 Mashima, H., 416 Mashima, K., 59, 153, 360 Mashukov, V.I., 349 Massah, A.R., 442 Masson, G., 263 Masuba, Y., 1 Masuda, K., 61 Masuda, M., 57 Masuda, Y., 36 Masui, R., 380 Masui, Y., 317 Masuyama, Y., 42 Mata, Y., 160 Matano, Y., 288 Mateo, C., 419 Mathew, T., 209, 435, 450 Mathies, A.K., 346 Matin-Mingot, A., 243 Matla, A.S., 234 Matlengiewicz, M., 197 Matovic, R., 434 Matsubara, H., 105, 407 Matsubara, K., 296 Matsubara, R., 135 Matsubara, S., 73, 360, 437, 448 Matsuda, K., 443 Matsuda, S., 281, 354 Matsuda, T., 46, 71, 227, 247 Matsui, A., 419 Matsui, J., 438 Matsui, M., 380 Matsukawa, S., 452 Matsukawa, Y., 192 Matsuki, S., 192 Matsumiya, A., 101 Matsumoto, A., 235 Matsumoto, H., 321

Author Index

Matsumoto, K., 105, 143, 146, 354, 438 Matsumoto, S., 68 Matsumoto, T., 112, 160, 300, 434 Matsumura, S., 485 Matsumura, Y., 105 Matsunaga, S., 13, 17, 75, 123, 130, 143, 255, 270, 410 Matsunami, M., 283 Matsuo, J., 9 Matsuo, K., 92 Matsuo, T., 419 Matsuura, K., 112 Matsuya, Y., 401 Matsuzawa, H., 108 Matsuzawa, M., 43 Matt, D., 29 Mattson, A.E., 434 Matz, P., 231 Mauder, M., 179 Mauduit, M., 400 Maugel, N., 321 Mauleon, P., 143, 213 Maya, V., 375 Mayer, P., 231, 482 Maytum, H.C., 96 Mazuela, J., 149 Mazzanti, A., 379 Mba, M., 245 McArthur, K.A., 368 McClory, A., 46 McCooey, S.H., 173 McCulla, R.D., 337 McDermott, M.C., 68 McDonald, F.E., 470 McErlean, C.S.P., 99 McGuire, T.M., 452 McKay, D.J., 416 McLaughlin, E.C., 385 McLaughlin, M., 240 McLaughlin, M.A., 420 McMurray, J.S., 318 McNeill, E., 467 McNulty, J., 264, 305 McPheators, G., 452 Mealli, C., 162 Mecalizio, G.C., 240 Meciarova, M., 264 Medda, A.K., 224 Medeiros, M.R., 443 Medina, J.C., 455

Medio-Simon, M., 433 Meetsma, A., 149 Mehandale, N.C., 316 Mehdi, H., 264 Mei, K., 382 Mei, T.-S., 321 Mei, Y., 163 Mejica, C., 169 Melchiorre, P., 173, 284, 379 Melender, H.J., 153 Melhado, A.D., 144 Mello, R., 449 Melzer, B., 187, 339 Menant, C., 239 Menard, F., 2, 160 Menche, D., 367 Menchi, G., 281 Mendes, S.R., 421 Mendez, F., 201 Mendez, L.Y.V., 79 Menedez, J.C., 99 Meng, Q., 152 Menicagli, R., 300 Menon, S., 352 Menz, H., 221, 365 Menzel, H., 488 Menzel, K., 231 Merced, F.G., 153 Mercer, G.J., 40 Mercer, T.B., 203 Mercier, L.G., 434 Merey, G., 83 Merisor, E., 448 Merten, S., 231 Messerle, B.A., 266 Metalinos, C., 2 Methot, J.L., 200 Metza, J.T., Jr., 303 Metzger, A., 482 Metzner, P., 423 Meunier, S., 89 Meyer, C., 87, 280, 352 Meyer, N., 310 Meyer, W.H., 400 Mi, A.-Q., 375 Miao, H., 312 Micalizio, G.C., 240 Michaelis, D.J., 191 Michalik, D., 78 Michalik, J., 200

523

524

Author Index

Michaut, A., 401 Michaux, J., 269 Michel, C., 414 Michelet, V., 221, 225 Michelin, R.A., 245 Michida, M., 423 Mico, Y., 78 Micouin, L., 1335 Mielgo, A., 379– 380 Mieno, Y., 269 Mifsud, M., 129 Migake, Y., 108 Mignani, G., 247 Mignani, S., 365 Mihara, M., 483 Mihara, Y., 401 Mikami, M., 22 Mika, S., 448 Mikami, K., 123, 135 Mikhel, I.S., 135 Miki, K., 365 Milburn, R.M., 23 Milelli, A., 379 Milet, A., 414 Millan, A., 441 Miller, N.D., 338 Miller, S.J., 143 Mills, A.J., 152 Mills, P.M., 231 Minamino, S., 96 Minamitsuji, Y., 163 Minatti, A., 160 Minehan, T., 303 Mineno, T., 253 Mink, J., 245 Minnaard, A.J., 23, 25, 135 Minnihan, E.C., 221 Minozzi, M., 447 Minter, A.R., 61 Mioskowski, C., 89, 169, 300 Miranda, L.D., 201 Misaki, T., 351 Misawa, K., 354 Mishra, N., 460 Mishra, N.K., 177 Mishra, V., 460 Mitani, K., 338 Mitomi, K., 274 Mitsuda, M., 105 Mitsudo, K., 328, 390 Mitsudo, T., 192

Mitsukmori, S., 129 Mitzel, N.W., 89 Miura, K., 253, 366 Miura, M., 46, 50, 66, 231, 324, 338 Miura, T., 48, 50–51 Mi, X., 383 Miyabe, H., 160, 433 Miyaka, Y., 48 Miyake, H., 310 Miyakoshi, N., 46, 198 Miyamoto, K., 199, 262 Miyamoto, T., 117 Miyamoto, Y., 360 Miyashita, M., 434 Miyaura, N., 51 Miyoshi, K., 483 Miyoshi, N., 419 Miyoshi, T., 309 Mizukami, T., 105 Mizunashi, K., 278 Mizuno, N., 390, 437 Mizuochi, M., 416 Mizuta, S., 173 Mlinaric-Majerski, K., 231 Mnotoyoshi, H., 349 Mo, J., 337 Moberg, C., 153, 360 Mochida, I., 360 Mochinda, T., 425 Mochizuki, E., 84 Mochizuki, S., 440 Modarresi-Alam, A.R., 411 Mogi, H., 105 Mohamad, J., 247 Mohan, K.V.V.K., 244 Mohan, R.S., 270 Mohanty, S., 343 Moise, J., 400 Moiseev, S.K., 34 Mok, B.J., 291 Molander, G.A., 92, 314, 407 Molins, S., 318 Molna´r, A., 411 Moloney, M.G., 310 Momiyama, N., 32, 312 Mongin, F., 281, 309 Monguchi, D., 281 Monguchi, Y., 312, 317– 318 Monnier, F., 162 Montagne, C., 234 Montagnon, T., 313

Author Index

Montalvo, E., 455 Montel, F., 300 Montes, L., 470 Montgomery, I., 312 Montgomery, J., 57 Monti, C., 135 Moody, C.J., 99 Moon, J., 293, 467 Moon, J.H., 467 Moore, J.L., 57 Moorhouse, A.D., 453 Moorthy, J.N., 263 Moquist, P.N., 19 Mora, L., 87 Morales, C.L., 83, 456 Moran, W.J., 149 Moran-Ramallal, R., 83 Moreno, L., 353 Moreno-Manas, M., 318 Morey, J.V., 302 Morgan, B.J., 341 Morgan, B.S., 117 Mori, A., 61 Mori, H., 116 Mori, K., 288 Mori, M., 162 Mori, T., 199 Mori, Y., 89, 423 Moriarty, R.M., 389 Moriel, P., 43, 467 Moriguchi, H., 423 Morimoto, H., 17 Morimoto, I., 390 Morimoto, K., 353, 454 Morimoto, T., 269, 283, 375. 438 Mori, S., 317 Morishita, M., 354 Morishita, T., 101 Morita, E., 306 Morita, H., 416 Morita, N., 452 Moriuchi, T., 245 Moriya, C., 92 Moriyama, K., 281 Morken, J.P., 57, 149 Morokuma, K., 309 Morra, N.A., 247 Morreale, M.S., 483 Morris, J.A., 349 Morrthy, J.N., 263 Mortier, J., 91

525

Mortreux, A., 322 Mosconi, E., 469 Moses, J.E., 453 Moslin, R.M., 406 Motamed, M., 365 Motherwell, W.B., 458, 483 Motodate, S., 425 Motoki, R., 189 Motoyama, Y., 247, 360 Motoyoshi, H., 46 Motoyoshiya, J., 447 Mou, C.-Y., 237 Mousseau, J.J., 338 Mousseau, J.L., 338 Mousset, C., 350 Movassaghi, M., 163, 373, 452 Mo¨ws, K., 424 Moyeux, A., 235– 236, 312 Mozumber, S., 177 Mu, X.-J., 287 Mueller, A.J., 234 Mugica-Mendiola, I., 173 Muir, J.C., 179 Mukai, C., 46, 198 Mukai, R., 339 Mukaiyama, T., 14, 380, 423 Mukherjee, S., 33 Muldoon, J., 273 Muler, C., 57 Mu¨ller, C., 135 Mu¨ller, N., 181, 186, 338 Mu¨ller, P., 157, 213 Mu¨ller, T.J.J., 42 Mu¨ller-Bunz, H., 273 Mulrooney, C.A., 341 Mulzer, J., 434 Munch, H., 194 Munday, R.H., 339 Muniz, K., 324, 327 Munoz, L., 204 Munoz-Dorado, M., 83 Murahashi, S.-I., 312 Murai, K., 99 Murai, M., 879 Murai, T., 278, 306 Murai, Y., 283 Murakami, K., 46, 232 Murakami, M., 5, 46, 48, 50–51, 71, 227, 247, 314, 469 Murakami, Y., 262 Murali, C., 349

526

Author Index

Muramatsu, K., 278 Muramatsu, W., 201 Muramatsu, Y., 21 Muraoka, O., 447 Murase, H., 283 Murata, K., 152, 353 Murata, M., 1, 36 Murayama, H., 410 Murayama, T., 354 Murelli, R.P., 401 Murphy, J.A., 78, 452 Murphy, J.M., 51 Murray, G.J., 294 Murru, S., 356 Murry, J.A., 1, 390, 438 Murugan, A., 173 Musio, B., 91 Mustafa, S., 205 Muthusamy, S., 247 Mutoh, Y., 278 Mu¨u¨risepp, A.-M., 122 Muzart, J., 317, 349 Mwene-Mbeja, T.M., 75 Myers, E.L., 130 Naber, J.R., 416 Nachtsheim, B.J., 32, 75 Nagamine, T., 123 Naganawa, Y., 157 Nagano, H., 284 Nagano, T., 129, 447 Nagao, Y., 489 Nagaoka, H., 443 Nagarajan, R., 272 Nagasaka, T., 135 Nagasawa, K., 123 Nagase, R., 351, 438, 447 Nagashima, H., 247, 360 Nagashima, T., 208 Nagata, K., 173 Nagata, M., 1 Nagawa, K., 123 Nagumo, S., 166 Naidu, A.B., 18 Nair, J.J., 264 Nair, R., 461 Naito, H., 187 Naitoh, Y., 237, 339 Najera, C., 17, 134, 372, 454 Nakada, M., 194

Nakagawa, H., 129 Nakagawa, Y., 288 Nakahara, K., 99 Nakai, T., 283 Nakajima, K., 488 Nakajima, N., 166 Nakama, K., 365 Nakamoto, E., 328 Nakamula, I., 79 Nakamura, A., 221, 306 Nakamura, E., 84, 231, 235, 259 –260 Nakamura, H., 349 Nakamura, I., 211, 255, 365 Nakamura, M., 231, 259– 260, 438 Nakamura, S., 105, 116, 173, 309–310, 450 Nakamura, Y., 452 Nakane, D., 105 Nakanishi, W., 135, 199 Nakanishi, Y., 365 Nakano, K., 143 Nakano, M., 288 Nakao, Y., 47, 50, 57, 310 Nakase, A., 410 Nakashima, D., 24 Nakata, K., 241, 310 Nakata, M., 169 Nakata, T., 407 Nakatani, Y., 186 Nakayama, H., 313 Nakazaki, A., 407 Nakazawa, S., 438 Nakazawa, T., 61 Nam, H., 467 Nam, W., 23 Namba, K., 288 Namboodiri, V.V., 270 Namiki, A., 38 Nandy, S.K., 318 Nanjo, M., 349 Nanni, D., 447 Napier, S., 433 Narasaka, K., 8, 390 Nardi, M., 205, 475 Narender, N., 244 Narender, R., 367 Narsaiah, A.V., 191 Narumi, M., 469 Narumi, T., 38 Nash, I.A., 369 Nasielski, J., 237

Author Index

Nasrollahzadeh, M., 411 Naubron, J.-V., 45 Naumiec, G.R., 324 Navarre, L., 71 Navarro, C., 59 Nechab, M., 105 Neels, A., 342 Negishi, E., 309 Negri, S., 433 Neisius, N.M., 401 Nelson, A., 7 Nelson, T.D., 231 Nemati, N., 32 Nemeth, J.A., 413 Nemoto, H., 401, 423 Nemoto, M., 441 Nemoto, T., 112 Neudo¨rff, J.M., 173 Neumann, E., 144 Neumann, H., 339 Neumaun, E., 149 Neuville, L., 61 Nevarez, Z., 415 Newell, R.J., 203 Newington, I., 264 Newton, R., 280 Neya, S., 420 Ngai, M.-Y., 67, 129, 266 Ngeow, K.C., 57 Ngouansavanh, T., 263 Nguyen, A.N., 173 Nguyen, H., 380 Nguyen, H.M., 40 Nguyen, L.X., 99 Nguyen, M.T.T., 105 Ni, B., 382– 383 Ni, C., 306 Nicolaou, G., 358 Nicolaou, K.C., 71, 271 Nie, J., 135, 191 Nielsen, P., 402, 416 Niesz, K., 434 Nihei, H., 255, 291 Niikura, S., 231 Nilsson, P., 321 Nimje, R.Y., 379 Ning, S., 198 Niphakis, M.J., 324 Nishi, Y., 199 Nishibayashi, Y., 48, 108

Nishigaichi, Y.K., 478 Nishiguchi, I., 283 Nishiguchi, N., 354 Nishihara, H., 79 Nishihara, Y., 40 Nishii, Y., 447 Nishimoto, K., 208 Nishimoto, Y., 255, 257 Nishimura, M., 153 Nishimura, T., 49, 71, 135 Nishimura, Y., 84, 303 Nishitani, M., 262 Nishiuchi, M., 83 Nishiyama, H., 123, 247 Nishiyama, Y., 271 Nishizawa, M., 288, 410 Niu, M., 179 Niu, Y.-N., 383 Niwa, M., 380 Niwa, T., 341 Niyomura, O., 353 Nobuta, Y., 51 Noda, H., 410 Node, M., 262 Noguchi, K., 59, 71 Nokami, J., 259 Nolan, S.P., 10, 213, 400, 455 Noll, B.C., 406 Nomura, K., 73, 448 Nomura, N., 410 Nonoyama, N., 231 Nordschild, S., 438 Norinder, J., 235 Norman, D.W., 34 Norton, J.R., 447 Norton, M.G., 343, 349 Notte, G.T., 129 Novak, Z., 346 Nowak, I., 177 Nowrouzi, N., 460 Noyori, R., 63, 152 Numaguchi, J., 351 Nunez, A., 401 Oberdorf, C., 305 Obi, K., 383 Obora, Y., 43, 341, 460, 469 O’Brien, C.J., 237, 342– 343 O’Brien, E.M., 341 O’Brien, P., 105

527

528

Author Index

Occhipinti, G., 400 Ochiai, M., 199, 262, 389 Ochida, A., 227 O’Connor, M.J., 450 Oda, T., 36 Odabachian, Y., 222 Odedra, A., 198, 222, 365 Odo, S., 40 Oestreich, M., 68, 71 Ogasawara, Y., 390, 437 Ogata, A., 441 Ogata, S., 231 Ogawa, C., 129, 270 Ogoshi, S., 57 Oguchi, T., 242 Ogura, J., 70 Oh, C.H., 221 Oh, C.N.H., 434 Oh, H.-S., 337 Oh, K., 146 O’Hara, F., 379 Ohata, M., 434 Ohata, S., 166 Ohba, Y., 99 Ohe, K., 365 Ohfune, Y., 222 Ohhmura, T., 61 Ohkubo, M., 379, 440 Ohkubo, T., 201, 317 Ohkuma, T., 72, 152 Ohmatsu, K., 3 Ohmiya, H., 46, 57, 232, 238 Ohmura, H., 83 Ohmura, T., 5, 34 Ohno, H., 38, 187, 211, 338, 433–434 Ohsawa, Y., 434 Ohshima, T., 59, 255, 360 Ohshima, Y., 274 Ohshita, J., 101 Ohsima, T., 153 Ohsumi, M., 149 Ohta, H., 469 Ohta, K., 20 Ohta, M., 380 Ohta, T., 166, 434 Ohta, Y., 187 Ohtsu, M., 14 Ohtsuki, K., 92 Ohwada, T., 450 Oi, S., 346

Oiarbide, M., 123, 173, 379 Oisaki, K., 144 Oishi, S., 38, 187, 211, 338 Ojima, H., 401 Ojima, I., 112 Ojima, S., 321 Okada, M., 410 Okada, N., 354 Okada, T., 222, 389, 433 Okada, Y., 14 Okado, K., 6 Okamoto, K., 360 Okamoto, S., 440, 483 Okamoto, T., 105 Okano, A., 434 Okano, T., 372, 383 Okazaki, T., 453 Oki, H., 144 Okimoto, M., 79 Oksdath-Mansilla, G., 187 Okuda, H., 112 Okui, A., 312 Okuma, K., 163 Okutani, M., 423 Olah, G.A., 209, 450, 453 O’Leary, D.J., 400 Oliveira, B.L., 242 Oliverio, M., 205, 475 Olivo, H.F., 123 Olleivier, T., 75 Ollivier, J., 99, 239, 302 Olofsson, B., 163 Olsson, R., 231 Olsson, V.J., 42 Oltra, J.E., 419, 441 Omar-Amrani, R., 343 Omori, A.T., 205 Omote, M., 22, 116–117, 166 Omura, S., 96 Onaka, M., 317 Ong, W.W., 272 Onitsuka, K., 112, 341 Onizawa, Y., 471 Onodera, G., 43, 48 Onomura, O., 105 Onozawa, S., 57 Ooi, T., 3, 77, 123 Ooka, H., 72 Oonishi, Y., 57, 70 Oppel, C., 179

Author Index

Oppel, I.M., 358 Organ, M.G., 237, 342– 343 Oriyama, T., 247, 379 Oro, C., 413 Orpen, A.G., 34 Ortiz-Marciales, M., 153 Osada, J., 351 Osaka, T., 59 Osante, I., 293 O’Shea, P.D., 416 Oshima, K., 5, 46, 50, 57, 176, 187, 232, 234, 238, 306, 337– 338, 341, 452 Oshima, T., 84 Osorio-Lozada, A., 123 Osuka, A., 316 Oswald, B., 29 Otake, Y., 60, 71 Otani, T., 46, 255, 291 Othara, Y.l, 146 Othmiya, H., 176 Otoyama, T., 241 Otsuka, K., 105 Otsuki, K., 339 Ott, T., 45 Otte, K.M., 7 Ouali, A., 187 Outurquin, F., 244 Ouyang, P., 454 Ovaska, T., 407 Ovaska, T.V., 353 Overgaard, J., 379 Overman, L.E., 155, 410, 470 Owston, N.A., 66, 96 Oyamada, J., 261, 366 Ozaki, D., 166 ¨ zdemir, I., 322 O Ozeki, M., 262 Pace, R.D.M., 379 Pace, V., 368 Paciello, R., 112 Pada, A., 83 Padmapriya, A.A., 318 Paek, J.S., 321 Pagenkopf, B.L., 83, 247, 456 Painter, T.O., 64 Paira, M., 99, 441 Paixao, M.W., 117, 178 Palais, L., 135 Pale, P., 181, 222, 343, 481

Pallerla, M.K, 198 Palma, A.C., 270 Palmier, S., 25 Palmisano, G., 36 Paloma, C., 173 Palomo, C., 123, 379 –380 Pamies, O., 149, 160 Pan, D., 328 Pan, F., 270 Pan, S., 161 Pan, S.C., 129, 358 Pan, X., 305 Pan, Y., 257, 261 Pan, Y.-M., 321 Pandey, G., 288 Pandey, L.K., 435 Pandey, S.K., 338 Panek, J.S., 272 Panella, L., 149 Panja, C., 209, 453 Panne, P., 389 Pannecoucke, X., 244 Panyachariwat, N., 83 Paoletti, M., 99 Pape, A.R., 247 Pape, T., 89 Paptchikhine, A., 149 Paquette, L.A., 123 Paradas, M., 441 Pardasani, D., 368 Parida, B.B., 383 Park, D.I., 434 Park, E.J., 357 Park, H., 23, 373 Park, H.-G., 173 Park, H.-J., 434 Park, H.M., 434 Park, J., 194, 322 Park, J.H., 174, 213, 490 Park, J.-W., 47 Park, M.Y., 244 Park, S., 28 Park, S.B., 357 Park, S.R., 78 Park, Y.H., 92 Parker, A.J., 66, 96 Parker, J.S., 369 Park, S., 5 Parmentier, M., 191 Parmon, V.N., 349

529

530

Author Index

Parra-Hake, M., 152 Parrott III, R.W., 117 Parsons, A.F., 312 Parsons, A.T., 467 Parthasarathy, K., 166 Partridge, K.M., 438 Parvez, M., 365 Pasumansky, L., 200 Patel, B.K., 356 Patel, J., 123 Patel, J.J., 90 Patel, K.N., 417 Paterson, D.R., 99 Pathak, U., 435 Patil, Y.P., 318 Patman, R.L., 42, 266 Patra, P.K., 10 Patrick, B.O., 365, 440 Pattenden, L.C., 234 Patureau, F.W., 29 Paul, T., 401 Paull, D.H., 173 Pawar, S.S., 321 Pawluc, P., 85, 95 Payette, J.N., 144 Pedersen, H., 467 Pedro, J.R., 19, 23, 123, 144 Pedrosa, R., 135 Pedrozo, E.C., 248 Pehk, T., 122 Pei, D., 153 Pei, G.-J., 144 Pei, T., 231 Pellacani, K., 359 Pelletier, G., 191 Pelliser, H., 143 Pellissier, H., 105 Peltier, H.M., 86 Pena-Cabrera, L., 36 Penczek, R., 197 Penenory, A.B., 187 Peng, C., 433 Peng, D., 117 Peng, J., 467 Peng, Q., 112 Peng, Y., 380 Penon, O., 379 Penrose, S.D., 71 Perchyonok, V.T., 11 Peregrina, J.M., 401

Perez, A., 982 Perez-Arlandis, J.M., 264 Perez-Castells, J., 64 Perez-Luna, A., 302 Perez-Sanchez, I., 306 Pericas, M.A., 383 Perl, N.R., 400 Perman, J.A., 32 Perrault, C., 297 Perrio, S., 423 Perry, A., 7 Persiani, D., 321 Peruncheralathan, S., 410 Peschiulli, A., 173 Pesciaioli, F., 173 Pesciteli, G., 23 Peters, R., 144, 155, 174 Petersen, T.B., 349 Peterson, E.A., 108 Petit, S., 459 Petragnani, N., 421 Petrenko, A., 349 Petrovskii, P.V., 34 Petrucci, F., 318 Pettman, A., 152 Pettus, T.R.R., 263 Petursson, S., 203 Pevec, A., 201 Pews-Davtyan, A., 32 Pfaltz, A., 144, 149 Phansavath, P., 402 Phapale, V.B., 296 Phetmung, H., 34 Phillips, E.M., 10, 130, 155 Phillis, A.T., 278 Philouze, C., 105 Phukan, P., 187 Pi, S.-F., 101 Pianet, I., 122 Piao, Y., 87 Piarulli, U., 34, 135 Pickett, J.A., 401 Piera, J., 225, 312 Pierce, M.E., 2 Piers, W.E., 365 Pignataro, L., 117 Pilarski, L.T., 316 Pilati, T., 143 Pilotti, A., 321 Pinna, G.A., 467

Author Index

Pinto, A., 61 Piperno, A., 402 Piqueur, J., 84 Piras, L., 360 Piras, P.P., 302 Pissarek, J.-W., 310 Pittelkow, M., 194 Pitteloud, J.-P., 470 Pizzuti, M.G., 25 Plaskon, A.S., 453 Plastina, P., 350 Player, M.R., 244 Pletnev, A.A., 400 Plietker, B., 401, 424 Plummer, J.M., 406 Poh, C.Y., 261 Pohmakotr, M., 484 Poigny, S., 182 Poisson, J.-F., 338 Pola¨ckova´, V., 469 Polanc, S., 99, 485 Polet, D., 26 Poli, G., 338, 467 Polshettiwar, V., 270, 411 Pomerantz, W.C., 373 Poon, K.W.C., 456 Popowycz, F., 261 Porcel, S., 222, 412 Porco, J.A., Jr., 272, 415, 486 Porzelle, A., 187 Posner, G.H., 357 Potavathri, S., 324 Potter, R.G., 418 Potts, B.C.M., 368 Pouliquen, M., 130 Poulsen, T.B., 173 Pouvreau, S., 401 Pouy, M.J., 26 Powell, D.A., 191 Powell, L.H., 287 Prabhakar, A.S., 483 Prabhakaran, E.N., 447 Prabhudas, B., 194 Pradhan, P.P., 310 Pradidphoe, N., 269 Prakash, G.K.S., 209, 450, 453 Prapurna, Y.L., 257 Prasad, D.J.C., 18 Prashad, M., 289 Prati, F., 84

Pratihar, D., 200, 259 PraveenGanesh, N., 490 Preetz, A., 149 Prestat, G., 338, 467 Pridmore, S.J., 96 Prien, O., 23 Prieur, D., 369 Prim, D., 269, 343 Pringle, P.G., 34 Prins, L.J., 245 Probert, M.R., 23 Proch, S., 46 Procopia, A., 205, 475 Procopiou, P.A., 95 Proctor, D.A., 407 Prokopcova, H., 433 Provot, O., 247, 349–350, 365 Prunet, J., 287 Pu, D., 356–357 Pu, L., 23 Pucheault, M., 467 Pudas, M., 489 Puente, A., 379 Puget, B., 343 Puglisi, A., 410 Puleo, G.L., 375 Pulling, M.E., 447 Pumphrey, A.L., 389, 484 Punniyamurthy, T., 187 Punzi, A., 234 PurNIK, V.G., 278 Purushotham, M., 243 Putey, A., 261 Puthiaparambil, T.T., 79 Qi, M.-H., 84, 352 Qi, M.-J., 14 Qi, X., 181 Qi, Y., 243 Qian, Q.-F., 287 Qiao, Y., 383 Qiao, Y.-F., 123 Qin, B., 123, 129 Qin, C., 322, 324, 467 Qin, H., 75 Qin, J., 201 Qin, L., 356 Qin, W., 433 Qin, Y., 189, 322 Qin, Y.-C., 155

531

532

Author Index

Qiu, H., 117 Qiu, H.-Y., 257 Quan, J., 420, 485 Quan, L.G., 411 Quayle, P., 181 Que, L., Jr., 270 Queis, H.R., 373 Quiclet-Sire, B., 201 Quinn, J.F., 259 Raab, C.E., 442 Racicot, L., 356 Rad, M.N.S., 442 Raders, S.M., 443 Radius, U., 57 Raemy, M., 338 Raffa, P., 210 Raghavan, S., 205 Rahaim, R.J., Jr., 485 Rahaman, R.O., 224 Rahanath, O.R., 18 Raheem, I.T., 108 Rahmati, A., 437 Raiber, E.A., 91 Raimbault, S., 90 Raimondi, L., 17 Rainier, J.D., 439 Raithby, P.R., 71 Raj, M., 375 Rajagopal, G., 454 RajanBabu, T.V., 26 Rajesh, G., 469 Rajesh, K., 261 Rajpara, V.B., 227 Raju, R., 400 Ramachandran, P.V., 200, 259, 281 Ramana, C.V., 166, 196 Ramasastry, S.S.V., 122 Ramdhanie, B., 245 Raminelli, C., 101, 302, 423 Ramljak, T.S., 231 Ramon, D.J., 372 Ramtohul, Y.K., 101 Ranu, B.C., 87, 343 Rao, D.M., 261 Rao, H.S.P., 208 Rao, K.R., 261 Rao, Q.-Q., 32 Rao, W., 261 Rao, Y.G., 191

Rapp, M., 470 Rasmussen, L.K., 425 Rasta¨tter, M., 272 Rasul, G., 450 Rathgeb, X., 26 Rathore, K., 205 Ratovelomanana-Vidal, V., 152– 153 Rauf, W., 327 Rauhaus, J.E., 191 Rauter, A.P., 433 Ravasio, N., 177 Ravikanth, B., 99 Rawal, V.H., 123, 467 Ray, D., 338 Ray, J.K., 99, 338 Ray, S.C., 99 Ready, J.M., 181, 407, 489 –490 Reamer, R.A., 1, 458 Reboule, I., 406 Rech, J.C., 129 Reddy, B.V.S., 191 Reddy, C.R., 367, 383, 469 Reddy, C.S., 417 Reddy, C.V., 337 Reddy, K.S.K., 244 Reddy, M.S., 186 Reddy, P.N., 421 Reddy, P.P., 483 Reddy, P.R., 421 Reddy, P.V.G., 264 Reddy, R.P., 144 Reddy, V.S., 261 Reddy, Y.T., 421 Redert, T., 337 Redford, J.E., 484 Redlich, S., 488 Redon, S., 244 Reed, S.A., 327 Reek, J.N.H., 29 Reetz, M.T., 34 Reeves, D., 149 Reeves, J.T., 10, 448 Reichard, H.A., 240 Reichle, M., 108 Reilly, J.E., 79 Reiner, J., 269 Reingruber, R., 300 Reisinger, C.M., 173 Reisman, S.E., 108, 407 Reissig, H.-U., 407

Author Index

Remme, N., 410 Ren, H., 482 Ren, X., 454 Renard, P.-Y., 123 Renaud, J.-L., 461 Renaud, P., 11, 241, 301 Renault, J., 208, 349 Renoux, B., 243 Repic, O., 289 Retailleau, P., 338, 447 Reuping, M., 33, 75 Reutrakul, V., 484 Revell, J.D., 375 Reyes, E., 379 Reymond, S., 236 Reynolds, S.C., 306 Reynolds, T.E., 10, 89, 130, 155, 278, 410 Rheam, M., 407 Rhee, H., 312 Rhee, Y.H., 221–222 Rheingold, A.L., 455 Riant, O., 123 Ribas, X., 270, 287 Ribeiro, R.S., 242 Ricard, L., 201 Richardson, R.D., 263 Richel, A., 196 Richter, J.M., 449 Rickerby, J., 144 Rieguet, E., 297 Riente, P., 293 Riera, A., 459 Riesgo, L., 169, 365 Rinner, U., 411 Rios, R., 373, 379 Ritter, T., 400 Rivera-Otero, E., 105 Rivero, M.R., 187 Rix, D., 400 Robak, M.T., 130 Robert, F., 87, 241 Robert-Peillard, F., 157 Roberts, S.W., 155 Robertson, A., 264 Robins, M.J., 177 Robles, R., 441 Roblin, J.-P., 343 Roche, C., 402 Rodrigue, E.M., 221 Rodrigues-Santos, C.E., 479

533

Rodriguez, B., 372 Rodriguez, F., 221, 240 Rodriguez, J., 400 –401 Rodriguez, N., 179, 187, 339, 433 Rodriguez, R., 84 Rodriguez-Garcia, I., 83 Rodriguez-Solla, H., 169, 285, 403, 406, 417 Roelfes, G., 144 Roesky, P.W., 272, 310 Rogachev, V.O., 231 Rogers, M.M., 324, 341 Rogers, R.L., 57 Rohbogner, C.J., 285 Roig, A., 318 Rollin, P., 433 Roman, B., 365 Romanelli, G.P., 244 Romeo, G., 402 Romeo, R., 402 Rominger, F., 263 Romo, D., 234, 356, 380 Roncaglia, F., 312 Rondot, C., 447 Ros, A., 153 Rosati, O., 205 Rosset, S., 135 Rossignol, E., 369 Rostami, K.A., 83 Rostovtsev, V.V., 425 Rouden, J., 130, 173 Roush, W.R., 448 Rout, L., 187 Routaboul, L., 45 Rovis, T., 10, 57, 105, 160, 196 Rowland, E.B., 32, 105 Rowland, G.B., 32, 105 Rowley, J.M., 425 Roy, M., 99, 343 Roy, S., 343 Roy, S.C., 441 Royer, J., 300 Royo, M., 242 Rozen, S., 249 Rozenman, M.M., 450 Ruan, J., 2, 337 Rubenhauer, P., 75 Rubio, R.J., 42 Ruchirawat, S., 83 Ruck, R.T., 349 Rudolph, A., 338

534

Author Index

Rudolph, S., 367 Rudolphi, F., 179 Rue, N.R., 324 Rueck-Braun, K., 467 Rueping, M., 32, 236 Ruff, C.M., 42 Ruiz-Rodriguez, J., 242 Rujiwarangkul, R., 85 Rule, S.D., 203 Ruppel, J.V., 143 Russo, A., 375 Ryabova, V., 349 Ryabukhin, S.V., 453 Ryan, S.J., 11 Ryoda, A., 135 Ryu, D.H., 7 Ryu, I., 96, 105, 402 Ryu, J., 146 Saa, C., 462 Sabot, C., 356 Sacchetti, A., 143 Sadani, A.A., 379 Sadighi, J.P., 213 Sadoui, M., 467 Safronov, A.S., 112 Sagae, H., 71 Sahe, A., 149 Sai, M., 234 Saicic, R.N., 434 Said-Galiev, E.-E., 34 Saidi, O., 2 Saikawa, Y., 169 Saino, N., 483 Saito, A., 60, 351 Saito, B., 108, 296 Saito, H., 349 Saito, M., 291 Saito, N., 57 Saito, S., 51, 57, 135, 186, 242, 353 Saito, T., 46, 153, 255, 257, 291 Saitoh, H., 231 Saitoh, I., 61 Sajiki, H., 312, 317–318 Sakaguchi, A., 105 Sakaguchi, K., 222 Sakaguchi, S., 43, 460 Sakai, J., 61 Sakai, K., 306 Sakai, N., 181, 283

Sakakura, A., 201, 351 Sakamoto, T., 309, 353 Sakata, K., 48 Sakita, K., 314 Sako, S., 318 Sakonaka, K., 68 Sakurai, A., 318 Sakurai, H., 312 Sakurai, T., 321 Salama, T.A., 483 Salas, G., 310 Salehi, P., 411 Salem, B., 434 Salerno, G., 350 Salian, S.R., 166 Salmi, C., 416 Salter, M.M., 19 Salter, M.W., 20 Salvadori, P., 23, 210 Salvi, L., 92 Samanta, S.S., 91 Sambri, L., 173, 284, 379 Samec, J.S.M., 400 Sames, D., 321 Sammakia, T., 8 Samojlowicz, C., 400 San Andres, L., 99 Sanchez, F., 211 Sanchez-Rosello, M., 401 Sandee, A.J., 29 Sanderson, A., 105 Sandmann, R., 70 Sanford, M.S., 40, 327, 356 Sangu, K., 291 Sanjiki, H., 478 SanMartin, R., 181, 353 Sannohe, Y., 144 Sano, D., 173 Sano, H., 321 Sano, S., 489 Sano, T., 440 Sano, Y., 241 Sansano, J.M., 454 Santamarta, F., 257 Santelli, M., 38, 273, 438 Santu, P.S., 261 Sanz, R., 92 Sarandeses, L.A., 294 Saritha, D., 257 Sarkar, D., 437

Author Index

Sarkar, S.M., 117 Sarpong, R., 365–366 Sartori, G., 413 Sasai, H., 22, 112, 123, 341 Sasaki, I., 288, 410 Sasaki, M., 278, 310, 434 Sasaki, S., 123 Sasaki, Y., 112 Sashida, H., 402 Sashuk, V., 400 Sasikanth, S., 483 Sasraku-Neequaye, L., 231 Sasson, Y., 352, 473 Sastre-Santos, A., 257 Sastry, M.N.V., 99 Sata, J., 79 Sathapornvajana, S., 375 Sato, A., 10 Sato, H., 83, 135 Sato, I., 380 Sato, K., 116–117, 166, 231, 375, 438 Sato, T., 101, 211, 410, 470 Sato, Y., 57, 70, 162 Satoh, C., 306 Satoh, T., 46, 50, 66, 231, 306, 324, 338 Satrustegui, A., 221 Satyanarayana, T., 117 Saudan, C.M., 73 Saudan, L.A., 73 Sauer, S.J., 284 Saunders, L.B., 321 Sauthier, M., 322 Savarin, C., 416 Savarin, C.G., 1 Sawamura, M., 112, 227 Sayah, M., 343 Sayo, N., 59, 153 Sayyed, I.A., 200 Sayyed, L.A., 178 Scammells, P.J., 262 Scarso, A., 245 Scattolin, E., 177 Schacherer, L.N., 443 Schade, M.A., 482 Schafer, L.L., 440, 486 Scha¨ffner, B., 78, 112, 149 Schareina, T., 181, 186, 338 Schaub, T., 57 Schaus, S.E., 19, 129 Scheeren, H.W., 208

535

Scheerer, J.R., 423 Scheidt, K.A., 10, 89, 130, 155, 278, 410, 434 Schenk, K., 87, 241 Schenkel, L.B., 86 Schetter, B., 21 Schiaffo, C.E., 314 Schipper, D.J., 338 Schla¨ger, T., 305 Schleicher, K.D., 57 Schmidbauer, H., 475 Schmidt, F., 173 Schmidt, G., 169 Schmidt, M.A., 163 Schmidt, S., 4 Schnakenburg, G., 21 Schneekloth, J.S., Jr., 467 Schneider, C., 32, 105, 259, 410 Schneider, P.H., 117 Schneider, R., 343 Schneider, U., 129, 258 Schoenebeck, F., 78 Schomaker, J.M., 410 Scho¨n, S., 310 Scho¨nberg, H., 266 Schreiber, S.L., 221 Schreiner, P.R., 203 Schrekker, H.S., 169 Schrems, M.G., 149 Schriner, P.R., 285 Schrock, R.R., 400, 411 Schrodi, Y., 400 Schulz, E., 17, 144 Schulz, S.R., 123, 310 Schumers, J.-M., 360 Schwarz, C.A., 284 Schwarz, N., 200, 485 Schweikert, T.S., 390 Schweizer, S., 433 Schwier, T., 221 Scobie, M., 247 Scott, M.E., 284 Scott, T.L., 318 Seayad, J., 10 Sebastian, R.M., 318 Sebelius, S., 316 Sebesta, R., 149 Secci, F., 302 Sedelmeier, G., 300 Seehasombat, P., 484 Seggio, A., 281, 309

536

Author Index

Segura, A., 60 Sehnem, J.A., 112 Seidel, T.M., 61 Seifried, D.D., 64 Seiler, P., 155 Seiser, T., 231 Sekar, G., 18, 86 Sekhar, E.R., 257 Seki, K., 19 Seki, R., 57 Sekiguchi, Y., 135 Selander, N., 316 Selim, K., 105 Selvam, J.J.P., 261 Semenischeva, M., 421 Semenischeva, N.I., 417 Sen, S., 243 Senanayake, C.H., 10, 149, 401, 448 Senapatai, K., 263 Sendelmeier, J., 123 Sengmany, S., 483 Seo, J.W., 439 Seo, S.Y., 272 Seomoon, D., 253, 469 Sereda, G.A., 227 Seregin, I.V., 349 Sergeev, A., 339 Serna, P., 210 Serna, S., 353 Serrano, O., 433 Servais, A., 447 Servesko, J., 489 Servesko, J.M., 149 Serwatowski, J., 89 Sessler, J.L., 261 Sestelo, J.P., 294 Sgarbossa, P., 245 Sha, J., 411 Shaﬁr, A., 186–187 Shaikh, N.S., 153, 367 Shair, M.D., 123 Shan, W., 478 Shan, Z., 484 Shang, D., 375 Shankaraiah, N., 417 Shao, L.-X., 84, 352 Shao, P.-L., 143 Shapiro, N., 312 Shapiro, N.D., 213, 222 Sharma, A., 461

Sharma, G., 207 Sharma, P.K., 402, 416 Sharma, V., 283 Sharpless, K.B., 187 Shashidhar, M.S., 349 Shaw, J.T., 485 Shaw, M.L., 339 She, D., 179 She, N., 261 She, X., 305 Shefer, N., 249 Shei, C.-T., 87 Sheldon, R.A., 453 Sheldrake, H.M., 482 Shen, H.C., 221 Shen, K., 454 Shen, L., 189 Shen, M., 389, 484 Shen, Q., 269, 403, 443 Shen, W., 490 Shen, W.-Y., 152 Shen, Y., 257 Shen, Y.-X., 346 Shen, Z., 157 Shen, Z.-L., 253 Sheng, J., 416 Sheng, Q., 199 Sheppard, T.D., 458, 483 Shepperson, I.R., 19 Shermer, D.J., 67 Sherry, B.D., 67, 213 Shevlin, M., 349 Shi, B.-F., 160 Shi, C., 112 Shi, F., 101, 423, 425 Shi, L., 270 Shi, M., 7, 14, 17– 18, 84, 247, 278, 346, 352, 444, 456 Shi, W., 426 Shi, Y., 28, 86, 146, 181, 187, 434, 454 Shi, Y.-L., 14 Shi, Z., 257, 312, 324, 346 Shi, Z.-J., 237, 269, 324 Shibahara, F., 96 Shibasaki, M., 13, 17, 75, 123, 130, 134, 143 –144, 189, 255, 410 Shibata, I., 195, 257, 443 Shibata, N., 105, 116, 173 Shibatas, T., 71 Shibuya, M., 423, 435

Author Index

Shiers, J.J., 234 Shigeno, M., 71 Shigetomi, T., 163 Shiina, I., 241 Shimada, M., 48 Shimada, T., 222 Shimada, Y., 146, 438 Shimamura, S., 406 Shimazawa, R., 38, 375 Shimizu, H., 50, 153 Shimizu, M., 3, 46, 73, 89, 197 Shimizu, Y., 43 Shimokawa, J., 204, 460 Shimp, H.L., 240 Shin, S., 221– 222 Shinde, S.S., 101 Shindo, M., 92 Shingare, M.S., 321 Shinohara, A., 13 Shinokubo, H., 316 Shinokura, T., 288 Shintani, R., 5, 28, 47, 50, 70– 71, 144, 236 Shiomi, T., 123 Shipman, M., 234, 458 Shirai, R., 38, 375 Shiraishi, T., 303 Shirakawa, E., 235–236 Shirakawa, K., 79 Shirakawa, S., 77 Shirakura, M., 57 Shiro, M., 199, 489 Shishido, K., 92, 433 Shitami, H., 143 Shivanyuk, A.N., 453 Shizuka, M., 135 Shoji, M., 6, 372 Shoji, T., 391 Shokouhimehr, M., 87 Shorshnev, S.V., 293 Shou, W.-G., 179, 458 Shreeve, J.M., 343, 349 Shu, C., 401 Shu, L., 146 Shu, X.-Z., 419, 433 Shuklov, I.A., 112 Siamaki, A.R., 469 Sibi, M., 135 Sickert, M., 32 Sidda, R.L., 458 Sido, A.S.S., 181

Sieber, J.D., 57 Sieburth, S.M., 243 Sierra, M.A., 321 Siewert, J., 70 Sigman, M.S., 146 Signore, G., 300 Sikkander, M.I., 453 Sillanpa¨a¨, R., 117 Silva, L.F., Jr., 248 Silva, S., 433 Silvani, A., 143 Silveira, C.C., 421 Silverman, S.M., 28 Sim, S.H., 46, 434 Simaan, S., 302 Simal, C., 403, 406 Simard, D., 454 Simeone, J.P., 318 Simonini, V., 117 Simpkins, N.S., 89 Simsek, S., 123 Sindelar, R.W., 129 Sindona, G., 475 Singaram, B., 153, 200, 417 Singaram, S.W., 365 Singh, A., 130 Singh, C.B., 356 Singh, O.V., 26, 287 Singh, R.P., 174 Singh, S., 454 Singh, S.K., 186 Singh, S.P., 444 Singh, V.K., 375 Singhal, N., 263 Sinha-Mahapatra, D., 352 Sinha-Mahapatra, D.K., 169 Sinishtaj, S., 357 Sinisi, R., 178 Sinisterra, J.V., 368 Siqueira, F.A., 248 Sirasani, G., 401 Sirlin, C., 343 Sit, W.N., 327 Skouta, R., 225 Skrydstrup, T., 349, 467 Skucas, E., 59, 266 Slaba, R.L., 227 Slatford, P.A., 67, 96 Slawin, A.M.Z., 99 Smejkkal, T., 2

537

538

Author Index

Smith, B.M., 259 Smith, C.J., 407 Smith, C.R., 26, 447 Smith, D., 263 Smith, D.M., 447 Smith, J.M., 247, 447 Smith, K., 281 Smith III, M.R., 51 Smith, R.C., 38 Smith, S.A., 234 Smith, S.M., 29 Snapper, M.L., 129, 135, 401 Sneddon, H.F., 155 Snell, R.H., 413 Sniady, A., 483 Snieckus, V., 23 Snowden, T.S., 423 Soai, K., 117 Sobjerg, L.S., 467 Sodeoka, M., 3, 68 So¨derberg, B.C.G., 61, 318 Soderquist, J.A., 79, 455 Sodoka, M., 108 Soeta, T., 105, 135 Soga, K., 32 Sohn, M.-H., 101 Sohn, S.S., 10 Sohtome, Y., 123, 143 Sokeirik, Y.S., 116, 166 Sokol, A., 473 Soldaini, G., 473 Soldi, L., 413 Sole, D., 433 Soler, R., 318 Somanathan, R., 152 Someya, H., 176, 232, 234, 238 Somfai, P., 80 Sommer, J., 181, 481 Son, S., 144 Sonavane, S.U., 352 Sone, T., 143, 242 Sonenfeld, D., 473 Song, B., 312 Song, D., 83, 255, 356 Song, F., 224 Song, J., 28 Song, J.I., 200 Song, J.J., 10, 448 Song, L., 382 Song, M.-P., 116 Song, R.-J., 177

Son, S., 296 Song, Z., 202, 346 Sorensen, T.S., 365 So¨rgel, S., 407 Sorimachi, H., 72 Sorimachi, K., 32 Soto-Cairoli, B., 79 Sottocornola, S., 36 Soua, T., 259 Souﬁaoui, M, 146 Soumeillant, M., 341 Souto, A., 84 Sowa, J.R., Jr., 318 Spafford, M.J., 270 Spaggiari, A., 84 Spagnolo, P., 447 Spannenberg, A., 45, 78, 200 Sparling, B.A., 406 Spek, A.L., 57 Spengler, J., 242 Sperotto, E., 186 Sperry, J., 99 Spiegel, D.A., 443 Spiga, M., 302 Spilker, B., 267 Spivey, K.M., 489 Sprengers, J.W., 342 Sreedhar, B., 343 Sreekanth, A.R., 410 Sridharan, V., 99 Srinivas, Y., 367 Stadler, M., 373 Stahl, S.S., 7, 312, 324, 327, 341 Stainforth, N.E., 130 Stambuli, J.P., 28 Stamford, A., 99 Stanway, S.J., 281 Stara, IG., 57 Stary, I., 57 Stas, S., 83 Stashenko, E.E., 79 Stavber, S., 261 Stavber, S., 261 Stead, D., 105 Steart, I.C., 410 Steck, P.L., 300 Steekanth, A., 266 Stefane, B., 99 Stefani, H.A., 83, 178 Stefania, R., 419 Stein, D., 266

Author Index

Steinke, J.H.G., 400 Stemmler, R.T., 149 Stengel, B., 89 Stepanenko, V., 153 Stephan, D.W., 78 Stephenson, G.R., 68 Stepieri, M., 261 Stern, C.A., 10 Steward, O.W., 486 Stewart, I.C., 400 Stick, R.V., 251 Stiles, D.T., 112 Stimson, C.C., 188 Stivala, C.E., 155, 262 Stockman, R.A., 231 Stockman, V., 144 Stokes, B.J., 389, 484 Stoltz, B.M., 424 Stoncius, S., 149 St-Onge, M., 231 Straub, B.F., 68 Streuf, J., 324 Stropnik, T., 485 Strotman, N.A., 178, 296 Stru¨bing, D., 225 Strukul, G., 245 Stryker, J.M., 231 Stuart, D.R., 341 Studer, A., 47, 72, 310 Stuhler, H., 475 Stymiest, J.L., 306 Su, H., 174 Su, J., 64 Su, S., 415 Su, W., 322, 347, 410, 467 Su, Y., 328 Su, Z., 123 Suda, T., 59 Sudo, T., 63 Suematsu, H., 143 Suemune, H., 166 Suffert, J., 434 Sugai, S., 89 Sugai, T., 313 Sugawara, Y., 411, 413, 433 Sugimoto, H., 450 Sugimoto, K., 434 Suginome, M., 5, 34, 57, 61 Sugioka, T., 442 Sugiono, E., 32 Sugita, T., 441

Sugiyama, H., 105 Sugiyama, Y., 312 Sugizaki, K., 46 Sugizaki, S., 72 Sulzer-Mosse, S., 135 Sumida, Y., 57 Sumiya, T., 372 Sun, C., 312 Sun, C.-H., 321 Sun, C.-L., 324 Sun, C.-S., 38 Sun, H.-B., 257 Sun, J., 153, 383 Sun, L., 296 Sun, P., 174 Sun, X, 92, 152, 266, 269, 411 Sun, X.-L., 458 Sun, X.-W., 253 Sun, X.-X., 32 Sun, Y., 152, 454 Sun, Z., 129 Sun, Z.-P., 237, 269 Sung, K., 87 Suresh, D., 343 Suresh, E., 247, 454 Suresh, V., 261 Sureshkumar, G., 210 Suryakiran, N., 261 Suto, Y., 130 Suyama, T., 46, 291 Suzenet, F., 433 Suzuka, T., 438 Suzuki, K., 10, 72, 300, 312 Suzuki, T., 61, 108, 123, 274, 288, 341 Suzuki, Y., 433 Sviridov, S.I., 293 Svoboda, V., 488 Swager, T.M., 166 Sweeney, J.B., 34 Sydnes, M.O., 318 Sylla, B., 433 Szabo, K.J., 42, 316 Szadkowska, A., 400 Szatmari, I., 117 Szczepankiewicz, S., 400 Szekelyhidi, Z., 434 Szymoniak, J., 239 Tabatabaeian, K., 402 Taber, D.F., 453 Tada, M., 208

539

540

Author Index

Tada, N., 199, 262, 389 Tadaoka, H., 59, 153 Taddei, M., 360 Taduri, B.P., 365 Taft, B.R., 177, 349 Tagarelli, A., 475 Taggi, A.E., 173 Tago, S., 221 Taguchi, T., 300, 426 Tahara, Y., 71 Taillefer, M., 187 Taillier, C., 289 Taira, A., 410 Taira, T., 79 Tajbakhsh, M., 194 Takacs, J.M., 29 Takada, K., 123 Takadea, M., 50 Takagi, E., 418 Takagi, K., 40 Takahara, H., 401 Takahashi, A., 300, 426 Takahashi, H., 13 Takahashi, K., 75 Takahashi, M., 240 Takahashi, Y., 19, 50 Takahashi, S., 306 Takahashi, T., 488 Takahashi, Y., 312 Takai, K., 84, 259, 385 Takaki, K., 75, 269 Takano, Y., 441 Takasaki, M., 360 Takata, K., 259 Takatsu, K., 70– 71 Takaya, J., 57, 291, 471 Takayama, H., 354 Takayanagi, S., 401 Takeda, H., 57 Takeda, K., 278 Takeda, M., 416 Takeda, T., 426, 441 Takeda, Y., 89 Takemiya, A., 192 Takemoto, Y., 160, 433 Takemura, N., 123 Takenaga, N., 163, 356, 454 Takenaka, N., 135 Takeshita, A., 135 Takeuchi, R., 43

Takeuchi, T., 84 Takikawa, H., 10 Takita, R., 255 Takizawa, S., 123 Takuwa, A., 478 Tamai, T., 48 Tamaki, K., 407 Tamaki, T., 339 Tamaru, Y., 339 Tambade, P.J., 318 Tamiri, T., 473 Tamm, M., 470 Tamura, K., 478 Tamura, O., 484 Tamura, S., 112 Tamura, Y., 484 Tan, K.L., 129 Tan, L., 438 Tan, X., 356 Tan, Z., 10, 257, 448 Tanabe, G., 447 Tanabe, Y., 48, 351, 438, 447 Tanaka, A., 318 Tanaka, D., 162 Tanaka, F., 129 Tanaka, H., 328, 390 Tanaka, J., 253 Tanaka, K., 59–60, 71, 169, 278, 337, 391 Tanaka, M., 57, 166 Tanaka, N., 117, 259 Tanaka, R., 478 Tanaka, S., 153 Tanaka, T., 3, 338, 433–434, 443 Tanaka, Y., 77, 134 Tane, Y., 283 Tang, C., 130 Tang, S., 305 Tang, W., 89, 153, 337 Tang, W.-J., 67 Tang, X.-Y., 456 Tang, Y., 379, 458 Tang, Z., 375 Tanguy, C., 239 Taniguchi, H., 34 Taniguchi, T., 447 Tanimizu, H., 271 Tanino, K., 434 Tanino, N., 266 Tank, R., 435 Tanuwidjaja, J., 86

Author Index

Tao, C.-Z., 187 Tarby, C.M., 341 Tardella, P.A., 359 Tarr, J.C., 123 Tarselli, M.A., 221 Tarui, A., 116–117, 166 Tashima, K., 354 Tasselli, M.A., 67 Tateyama, H., 401 Tatibouet, A., 433 Tatsumi, R., 438 Tavassoli, B., 96 Tay, A.H.L., 261 Tayama, E., 89, 289 Taylor, C.D., 400 Taylor, C.N., 99 Taylor, M.S., 166 Taylor, P.C., 400 Tehrani, K.A., 83 Teijeira, M., 257 Tellitu, I., 181, 353 Telvekar, V.N., 417 Temma, T., 312 Tenaglia, A., 162, 197, 365 Teng, T.-M., 222 Teo, Y.-C., 122, 129, 264 Tepley, F., 57 Terada, M., 32, 211, 365 Teraguchi, R., 425 Terajima, T., 231 Terao, J., 234, 237, 339, 434 Terauchi, N., 231, 306 Terrasson, V., 269 Terzian, R.A., 303 Teshima, N., 306 Teske, J.A., 162 Tewes, B., 305 Thacker, N.C., 29 Tham, F.S., 42 Thangadurai, D.T., 221 Thansandote, P., 338 Theissmann, T., 32 Therien, M.J., 89 Thiara, P.S., 108 Thibaudeau, S., 243 Thiery, E., 317 Thivolle-Cazat, J., 411 Thomas, O.P., 478 Thomas, S., 79 Thomason, D.W., 78

Thompson, B.B., 57 Thompson, J.L., 412 Thomson, R.J., 99 Thore, S.N., 321 Thornton, A.R., 389 Tian, G.-Q., 346 Tian, H., 490 Tian, S.-K., 74, 247, 454 Tian, S.-L., 324 Tian, T., 144 Tian, X., 89 Tietze, L.F., 300, 337 Tillack, A., 200, 485 Tilley, T.D., 192 Tilly, D., 91 Tilstam, U., 237 Ting, A., 129 Ting, C.-M., 222 Tiseni, P., 174 Tiseni, P.S., 144 Tius, M.A., 144, 417 Tiwari, B., 383 Tobisu, M., 7, 57 Tocher, D.A., 291 Todo, H., 234 Togaya, K., 84 Togni, A., 144, 452 Togo, H., 199 Toh, T.-P., 253 Tohma, H., 454 Tojo, E., 257 Tokunaga, M., 221, 341, 469 Tokuyama, H., 434 Toledo, F., 302 Toledo, F.T., 101 To¨lle, N., 300 Tolmachev, A.A., 453 Tolomelli, A., 469 Toma, Sˇ., 149, 264, 469 Toma, T., 204, 460 Tomas, M., 169, 365 Tomas-Gamasa, M., 467 Tomaselli, G.A., 245 Tomioka, K., 105, 146 Tomioka, T., 410 Tomita, K., 38 Tomita, M., 253 Tomita, T., 271 Tomita-Yokotani, K., 92 Tomizawa, M., 435

541

542

Author Index

Tomkinson, N.C.O., 187, 443 Tommasi, S., 178 Tomooka, K., 314 Tong, X., 312, 327 Tong, Z., 365 Tonzetich, Z.J., 411 Tornoe, C.W., 467 To¨rnroos, K.W., 231 Torrs, R., 321 Toru, T., 105, 116, 173 Toscano, R.M., 245 Toshima, K., 485 Toshimitsu, A., 437 Toste, F.D., 67, 143–144, 213, 221– 222, 410 Toueg, J., 287 Tougerti, A., 433 Toullec, P.Y., 221, 225 Toupet, L., 29, 162, 211 Toyo, T., 6 Toyoda, K., 71 Toyoshima, M., 6 Toyota, Y., 380 Trabano, A.A., 306 Trabocchi, A., 281 Tran, Y.S., 458 Trauner, D., 451 Trepanier, V.E., 271, 434 Tria, G.S., 71 Trifonov, A., 17 Trillo, B., 365 Trincado, M., 130 Trindale, A.F., 390 Troﬁmov, A., 458 Troin, Y., 343 Trost, B.M., 3, 28, 36, 46, 108, 112, 130, 135, 338, 467 Troupel, M., 483 Trushkov, I.V., 478 Trzoss, M., 144 Tsai, A.S., 47 Tsai, C.-H., 439 Tsai, F.-Y., 237, 343 Tsai, H.-H.G., 349 Tsang, D.S., 70 Tsao, W.-C., 365 Tscho¨p, A., 410 Tse, M.K., 146, 178, 245, 267, 327, 425 Tsogoeva, S.B., 134 Tsubogo, T., 135

Tsuboi, T., 46 Tsubouchi, A., 426, 441 Tsuchida, S., 433 Tsuchikama, K., 71 Tsuhako, A., 483 Tsuji, H., 84, 260 Tsuji, M., 253 Tsuji, T., 144 Tsuji, Y., 341, 469 Tsujihara, T., 341 Tsujita, H., 192 Tsukada, T., 312 Tsukamoto, H., 160, 342, 433–434, 443 Tsukamoto, M., 353 Tsukiyama, K., 117 Tsunoyama, H., 312 Tsuritani, T., 178, 231 Tsurugi, H., 46, 50, 324, 338 Tsutsumi, K., 152, 438 Tsvelikhovsky, D., 321 Tu, W., 196 Tuan, L.A., 7 Tuck, K., 11 Tudge, M., 416 Tudge, M.T., 123 Tuktarov, A., 489 Tundo, P., 244 Tunge, J.A., 434, 467 Turcaud, S., 300 Turner, G.L., 349 Turner, M.R., 61 Turner, P., 266 Tuttle, T., 78 Tuzina, P., 80 Twamley, B., 343, 349 Tyagi, S., 389 Tye, H., 433 Tymonko, S.A., 38 Tyutyunov, A.A., 34 Tzeng, Z.-H., 375 Tzschucke, C.C., 51, 269 Uang, B.-J., 117 Uchida, N., 181 Uchida, T., 143 Uchiyama, M., 281, 302, 309– 310 Uchiyama, N., 135 Uciti-Broceta, A., 242 Udagawa, S., 471 Udzu, T., 318

Author Index

Ueba, C., 312 Ueda, M., 77 Ueda, N., 478 Uematsu, Y., 77 Uemura, M., 306, 337 Uemura, S., 48 Uenishi, J., 241, 338 Ueno, A., 467 Ueno, K., 296 Ueno, M., 19, 43 Ueno, S., 26, 96 Uenoyama, Y., 78 Ueta, T., 1 Ueura, K., 46, 66 Ukai, K., 57 Ukai, Y., 51 Ukon, T., 21 Umakoshi, M., 10 Umani-Ronchi, A., 178 Umbarkar, S.B., 245 Umebayashi, N., 68 Umeda, J., 51 Umeda, R., 72 Umeda, S., 241 Umetsu, K., 221 Umezaki, S., 207 Ung, T., 400 Unger, J.B., 177 Unno, M., 321 Uno, H., 460 Uozumi, Y., 112, 343 Upadhyaya, D.J., 419 Urabe, H., 187, 478 Uraguchi, D., 123 Urbanska, N., 368 Urge, L., 434 Uriac, P., 208, 211, 349 Urushima, T., 383 Urz, Y., 192 Ustynyuk, N.A., 11 Usu, I., 4 Usui, S., 302 Uto, T., 46 Utsumi, N., 122, 129, 152, 379 Utsunomiya, M., 360 Uyanik, M., 437 Uziel, J., 253 Vaccari, D., 84 Vaghoo, H., 209

Vahdat, S.M., 194 Vaique, E., 122 Valdes, C., 169, 467 Valdivia, V., 146 Valente, C., 237, 342– 343 Valiulin, R.A., 306 Vallet, M., 144 Vallribera, A., 318 Vandenbossche, C.P., 444 van der Haas, R.N.S., 32 van de Weghe, P., 211, 349 van Hoeck, J.-P., 237 van Klink, G.P.M., 186 van Koten, G., 186, 316 van Marseveen, J.H., 32 Van dr Eycken, E.V., 433 Van Vranken, D.L., 469 Vaquero, J.J., 401 Vardelle, E., 243 Varela, J.A., 462 Vargas, F., 112 Varma, R.J., 270 Varsolona, R., 149 Varugese, S., 79 Vasantham, K., 208 Vasconcellos, M.L.A.A., 242 Vashehenko, V., 349 Vasil’ev, A.A., 293 Vassilikogiannakis, G., 313 Vasylyev, M., 46 Vate`le, J.-M., 370 Vaxelaire, C., 414 Vazquez, C., 153 Vazquez, P.G., 244 Veeranjaneyuu, B., 99 Vehlow, K., 400 Veiros, L.F., 390 Velilla, L., 380 Vellema¨e, E., 439 Venkataraman, K., 209 Venkateswaran, R.v., 437 Venkateswarlu, K., 261 Venkateswarlu, Y., 261 Ventura, D.L., 389 Vera, S., 379–380 Verdaguer, X., 459 Verendel, J.J., 149 Verevkin, S., 149 Verevkin, S.P., 78 Vergari, M., 359

543

544

Author Index

Verkade, J.G., 337, 443 Veron, J.-B., 91 Verteletski, P.V., 478 Vesely, J., 10, 373, 379– 380 Vicente, R., 38 Vieira, A.S., 83 Vieira, F.Y.M., 248 Vigalok, A., 312 Vijeender, K., 367 Vila, C., 19, 23 Vilaivan, T., 129, 375 Vilar, R., 400 Vilarrasa, J., 189, 444 Villemure, E., 341 Vimolratana, M., 455 Vincent, J.-M., 122 Vincente, R., 365 Vinci, D., 2 Viozquez, S.F., 17 Vishnumaya, Singh, V.K., 382 Viswanathan, R., 447 Viton, F., 144 Vitulli, G., 210 Vo, G.D., 38 Vo, N.T., 379 Vogel, P., 236 Vogel, S., 467 Vogler, T., 47 Vogt, D., 57 Voica, F., 47 Voigtritter, K., 400 Volante, R.P., 416 Volla, C.M.R., 236 Volochnyuk, D.M., 453 Vologzhanin, P.A., 112 von Chrzanowski, L., 57 von Zezschwitz, P., 70, 300 Vora, H.U., 10 Vornberger, W., 475 Voss, L., 451 Vougioukalakis, G.C., 400 Vovard-Le Bray, C., 162 Vuagnoux-d-Augustin, M., 135 Vulovic, B., 434 Vuong, K.Q., 266 Wada, K., 192 Wada, M., 419 Wada, S., 460 Wada, Y., 43

Wadamoto, M., 155 Waetzig, S.R., 434, 467 Waghmode, S.B., 321 Wagner, A., 346 Wakabayashi, K., 135 Wakasugi, D., 231 Wakepohl, H., 176 Wakita, K., 123 Walcarius, A., 343 Walczak, M.A.A., 63 Waldo, J.P., 101 Walker, S.J., 248 Walkington, A.J., 68 Walkowiak, J., 85 Wallace, D.J., 458 Wallace, T.W., 482 Waloch, C., 112 Walsh, P.J., 21, 92, 309 Walter, C., 71 Walz, I., 144 Wan, J., 257 Wan, L., 321 Wan, S., 490 Wan, W., 283 Wan, X., 312, 324, 346 Wang, A., 149, 326 Wang, B., 173, 356 Wang, B.-Q., 237, 269 Wang, B.-T., 383 Wang, C., 7, 130, 257, 375 Wang, C.-J., 135 Wang, D., 373, 400 Wang, D.-H., 321, 328 Wang, D.-W., 78 Wang, D.-X., 117, 123 Wang, D.-Y., 149, 337 Wang, E.-C., 318 Wang, F., 101, 123, 160 Wang, G., 485 Wang, G.C., 423 Wang, G.W., 327, 369 Wang, H., 356 Wang, H.-S., 321 Wang, J., 19, 64, 83, 173, 187, 224, 269 –270, 373, 379, 400, 403, 433, 458 Wang, J.-C., 321 Wang, L., 22, 77, 129 Wang, L.-M., 490 Wang, L.-P., 135, 383 Wang, L.-W., 117

Author Index

Wang, L.-X., 117, 152, 157 Wang, M., 77, 116, 146, 413 Wang, M.-C., 116–117 Wang, M.-S., 349 Wang, M.-X., 117, 123 Wang, N., 22, 321, 380 Wang, P., 248 Wang, Q., 23, 193, 208, 296 Wang, Q.-G., 458 Wang, R., 484 Wang, S., 312, 356, 380, 485 Wang, S.-X., 117, 123 Wang, S.-Y., 66 Wang, S.R., 269 Wang, T., 423 Wang, W., 117, 312, 373, 379, 382 Wang, X., 33, 149, 173, 208, 231, 312, 318, 321, 383, 454 Wang, X.-B., 78 Wang, X.-D., 116–117 Wang, X.-J., 375 Wang, Y., 64, 173–174, 237, 248, 324, 356, 379, 383, 385, 414, 433 Wang, Y.-C., 321 Wang, Y.-F., 135 Wang, Y.-G., 179, 187, 458 Wang, Y.-Q., 78, 174 Wang, Y.-Z., 122, 375 Wang, Z., 20, 153, 283, 470 Wang, Z.-J., 67 Wang, Z.-Q., 47 Wang, Z.-Y., 346 Wanner, M.J., 32 Ward, D.E., 372 Wardell, J.L., 317 Warren, J.E., 71 Wasa, M., 328 Watanabe, H., 99, 194, 234 Watanabe, M., 77, 130, 152, 169 Watanabe, S., 1, 36 Watanabe, T., 211, 262, 291, 312, 338 Watson, A.J.B., 306 Watson, D.A., 339 Watson, I.D.G., 38, 221 Weatherwax, A., 173 Weber, M., 178 Weedon, J.A., 458 Wegbe, J., 269 Wei, G., 486 Wei, H., 149

Wei, P., 454 Wei, S., 22, 153, 383 Wei, W., 322 Wei, X., 401 Weibel, J.-M., 343 Weil, T., 285 Weinreb, S.M., 193 Weise, C.F., 2 Weiss, M.M., 407 Weitgenant, J.A., 406 Weix, D.J., 20, 26 Welbes, L.L., 327 Welch, G.C., 78 Welton, T., 264 Wen, F., 356–357 Wen, Y., 123, 129 Wendeborn, S., 300 Wender, P.A., 63, 295 Wendlandt, J.E., 341 Weng, T.Q., 349 Weng, Y., 294 Weng, Z., 57 Wengryniuk, S.E., 306 Wennemers, H., 375 Werness, J.B., 89 Wesquet, A.O., 445 Wessjohann, L.A., 117, 169 West, F.G., 83–84, 414 Westaway, S.M., 310 Westermann, B., 117 Weymouth-Wilson, A.C., 203 Whatrup, D.J., 338 Wheatley, A.E.H., 302 Wheeler, K.A., 483 Wheelhouse, K.M.P., 369 White, M.C., 327 White, N.S., 155 Whiting, A., 23 Whitney, S., 66 Whittaker, D.T.E., 90 Whittaker, M., 433 Whittingham, W.G., 182 Widenhoefer, R.A., 213, 221 Wiedemann, S.H., 410 Wiesner, M., 375 Wiest, O., 406 Wilden, J.D., 291 Wilhelm, R., 264 Wilkinson, J.A., 91 Willaert, S., 401

545

546

Author Index

Williams, D.B.G., 339 Williams, J.M.J., 64, 66–67, 96 Williams, L.J., 198, 302 Williams, O., 247 Williams, R.M., 460 Willis, A.C., 278 Willis, M.C., 61, 130, 338 Wills, M., 105 Wilson, T.W., 17, 123 Wilting, J., 57 Wincewicz, R., 247 Wingad, R.L., 34 Winkel, A., 264 Winssinger, N., 204 Winter, M., 242 Wipf, P., 63 Wirth, T., 263, 353 Witham, C.A., 213 Wittlesey, M.K., 96 Witulski, B., 390 Wnuk, S.F., 470 Woerpel, K.A., 105, 191, 415 Woggon, W.-D., 372 Wolckenhauer, S.A., 389 Wolf, C., 86, 123, 237, 344 Wolf, J., 385 Wolfe, J.P., 337 Wolfer, J., 173 Wong, C.-M., 255 Wong, F., 375 Wong, F.M., 414 Wong, F.T., 10 Wong, K.-T., 186 Wong, K.Y., 112 Wong, M.-K., 370 Wong, R., 442 Wong, Y.-C., 176 Wongseripipatana, S., 354 Wood, J.L., 407, 443 Wood, M.C., 486 Wood, R.A., 203 Woodrow, M.D., 187 Woodward, S., 368 Wooten, A.J., 21 Worthy, A.D., 434 Wozniak, K., 400 Wu, A., 257, 261 Wu, B., 400 Wu, C., 169 Wu, C.-H., 318 Wu, F., 173

Wu, H., 322, 467 Wu, H.-L., 117 Wu, H.Y., 45 Wu, J., 269, 357, 415 Wu, K.-H., 21 Wu, L., 21, 327 Wu, L.-Y., 383 Wu, M.-C., 129 Wu, P.-Y., 117 Wu, P.R., 414 Wu, Q.Y.R., 414 Wu, T., 237 Wu, T.R., 19 Wu, W., 261, 414 Wu, W.-Y., 343 Wu, X., 2, 143, 149, 152, 274 Wu, X-J., 135 Wu, X.-L., 327 Wu, Y., 99, 189, 316, 321, 407 Wu, Y.-D., 112 Wu, Z.-J., 22 Wulff, W.D., 143, 169 Wu¨nderlich, S.H., 309 Wu¨nsch, B., 305 Wu¨rthwein, E.-U., 302 Wu´stenberg, B., 149 Wykes, A., 264 Wynne, E.L., 458 Wyss, P., 73 Xi, P., 22 Xi, Z., 7, 187, 237 Xia, A., 321 Xia, C., 483 Xia, G., 117 Xia, N., 187 Xia, Y., 224 Xiang, B., 442 Xiang, J., 225, 257, 485 Xiang, S.-K., 237 Xiang, Z., 225 Xiao, F., 224 Xiao, H.-Q., 419 Xiao, J., 2, 152, 328, 337 Xiao, J.-C., 343, 349 Xiao, L., 483 Xiao, W.-J., 123, 383, 401 Xiao, X., 123 Xiao, Y., 36 Xie, B., 356 Xie, C., 101, 402

Author Index

Xie, F., 38, 112, 152 Xie, H., 373, 379, 382 Xie, J., 467 Xie, J.-H., 152 Xie, M., 144 Xie, R., 383 Xie, Y.-X., 177, 191, 321, 383 Xin, J., 375 Xin, Z.-Q., 155 Xing, D., 312, 346 Xing, L., 318 Xiong, Y., 123, 375 Xu, B., 312, 423 Xu, C., 284 Xu, D., 28, 149, 310, 337 Xu, D.-Q., 135, 383 Xu, F., 390 Xu, F.-X., 255 Xu, H., 123, 237, 382 Xu, H.-W., 39 Xu, J., 108 Xu, J., 3, 21, 32, 312, 356 Xu, L., 153, 337, 441 Xu, L.-W., 257 Xu, M., 202, 372 Xu, M.-H., 47, 86, 253 Xu, P., 101 Xu, P.-F., 117 Xu, Q., 411 Xu, Q., 17– 18, 262 Xu, S., 32 Xu, X., 32, 202 Xu, X.-F., 149 Xu, X.-Y., 122, 375 Xu, Z., 467 Xu, Z.-J., 39 Xu, Z.-Y., 135, 383 Xue, F., 382 Xue, M.-X., 173 Xue, S., 310 Xue, Y., 130 Yabuuchi, T., 72 Yada, A., 57 Yadav, J.S., 191 Yagyu, N., 10 Yajima, N., 135 Yakura, T., 369 Yamada, H., 14 Yamada, N., 416 Yamada, R., 105, 116

547

Yamada, S., 105 Yamada, T., 153, 411, 413 Yamada, W., 411, 413 Yamada, Y., 231, 253 Yamada, Y.M.A., 343 Yamada, T., 489 Yamagami, T., 236 Yamagata, K., 84, 260 Yamagishi, U., 255 Yamagiwa, N., 75 Yamaguchi, A., 13 Yamaguchi, H., 6 Yamaguchi, K., 135, 278, 390, 437 Yamaguchi, M., 245, 303 Yamaguchi, R., 66, 266 Yamaguchi, S., 7, 235 Yamaguchi, Y., 77, 222, 227 Yamamoto, A., 5 Yamamoto, E., 112 Yamamoto, H., 11, 24, 34, 87, 117, 135, 144, 146, 288, 410, 437 Yamamoto, M., 360, 444 Yamamoto, R., 166 Yamamoto, S., 264 Yamamoto, Y., 51, 178, 211, 225, 255, 365, 453, 467 Yamamura, S., 425 Yamanaka, D., 270 Yamanaka, I., 312 Yamane, H., 231 Yamanoi, Y., 79 Yamaoka, Y., 160 Yamasaki, H., 1 Yamasaki, R., 186 Yamashita, F., 434 Yamashita, K., 105 Yamashita, Y., 19– 20, 26, 112, 135 Yamataka, H., 22 Yamauchi, Y., 48 Yamaura, R., 402 Yamazaki, T., 231 Yamazoe, S., 166 Yan, B., 346, 419 Yan, J., 357 Yan, K., 153 Yan, P., 312 Yan, Z.-Y., 383 Yanagisawa, A., 13, 72, 77, 105 Yanagisawa, S., 63 Yanai, H., 300, 426 Yang, B.-L., 247

548

Author Index

Yang, C.-F., 74 Yang, C.-Y., 221 Yang, D., 64 Yang, F., 22 Yang, G., 160, 312 Yang, G.-C., 253 Yang, H., 303 Yang, J., 40, 130, 266 Yang, J.W., 153, 373 Yang, L., 22, 32, 312, 338, 346 Yang, M., 179, 350 Yang, M.-S., 257 Yang, S., 70, 324 Yang, S.-D., 324 Yang, S.G., 244 Yang, T., 221 Yang, W., 194 Yang, X., 365 Yang, X.-B., 22 Yang, Y., 117, 149, 221, 380 Yang, Y.-H., 456 Yang, Y.-Y., 179, 458 Yang, Z., 123, 225, 346, 357, 485 Yano, K., 247 Yan, T.-H., 439 Yao, C.-F., 99 Yao, T., 337 Yap, G.P.A., 389 Yasuda, H., 484 Yasuda, M., 195, 255, 257, 443 Yasuda, N., 178, 231 Yasuhara, Y., 49 Yasui, Y., 433 Yasuike, S., 433 Yatsumonji, Y., 426 Yau, S.C., 443 Yazaki, R., 19 Ye, C., 343, 349 Ye, J., 379 Ye, J.-L., 22, 231 Ye, L.-W., 458 Ye, S., 63, 143 Ye, X., 312 Yee, N.K., 10, 401, 448 Yeh, C.-H., 295 Yeh, M.-C.P., 365 Yen, F.-W., 186 Yeo, Y.-L., 253 Yeom, C.-E., 194 Yeom, H.S., 221 –222 Yeung, C.S., 486

Yeung, Y.-Y., 85, 153 Yi, W.-B., 208 Yim, H.-S., 467 Yim, S.J., 306 Yin, C., 117 Yin, G., 261, 327 Yin, J., 442 Yin, M., 116 Yin, Z., 179 Ying, J.Y., 10, 57 Yip, S.F., 187 Yokogi, M., 4 Yokomori, Y., 163 Yokota, M., 84, 207 Yokota, Y., 166 Yokoyama, F., 284 Yokoyama, N., 135 Yokoyama, R., 43 Yokoyama, T., 43 Yonehara, M., 281, 309 Yoo, E.J., 187 Yoo, K.S., 321, 389 Yoo, M.-S., 173 Yoo, W.-J., 87, 179 Yoon, C.H., 321, 389 Yoon, C.M., 312 Yoon, S.-H., 360 Yoon, S.J., 222 Yoon, T.P., 191, 438 Yoon, Y.-J., 467 Yorimitsm, H., 238 Yorimitsu, H., 46, 50, 57, 176, 187, 232, 234, 306, 337– 338, 341, 452 Yorke, J., 321 Yoshida, H., 101 Yoshida, K., 153, 328, 390 Yoshida, M., 433– 434 Yoshida, S., 50, 413, 452 Yoshifugi, S., 402 Yoshikai, N., 235 Yoshikawa, N., 438 Yoshikawa, S., 467 Yoshikawa, T., 92 Yoshimitsu, T., 443 Yoshimura, A., 199, 389 Yoshimura, F., 434 Yoshimura, T., 204 Yoshinami, Y., 71 Yoshita, K., 390 Yost, J.M, 284 You, J., 22, 191, 383

Author Index

You, S.-L., 10, 26, 32, 157 You, T., 20 Young, C.S., 339 Youseﬁ, M., 411 Yraola, F., 242 Yshida, T., 198 Ysui, H., 234 Yu, B., 221 Yu, C., 478 Yu, C.-B., 78 Yu, C.-M., 291 Yu, F., 434 Yu, G.-A., 349 Yu, J., 32, 357 Yu, J.-Q., 160, 321, 328 Yu, J.-Y., 38 Yu, L., 321 Yu, M., 227 Yu, M.S., 380 Yu, P., 40 Yu, R., 161 Yu, R.T., 196 Yu, S., 129, 379 Yu, S.-B., 149, 337 Yu, W.-Y., 112, 153, 327 Yu, X., 272, 415 Yu, X.-Q., 22–23, 357, 434 Yu, Y., 188 Yu, Z., 144, 264, 349 Yu, Z.-X., 63–64, 356 Yuan, C., 64 Yuan, T.-T., 327 Yuan, W., 28, 181, 187, 434 Yuan, Y., 245, 257 Yuan, Z.-L., 346 Yudha, S.S., 385 Yudin, A.K., 36, 38, 70, 253 Yue, D., 337 Yue, H., 413 Yue, H.-D., 383 Yue, S., 245 Yue, Y., 414 Yuen, A.W.-H., 39 Yukawa, S., 269 Yuki, M., 48 Yuki, T., 166 Yum, E.K., 328 Yun, J., 149, 181 Yus, M., 25, 275, 280, 293, 433 Yusa, Y., 153 Yusubov, M.S., 245

549

Zaccheria, F., 177 Zacuto, M.J., 390 Zair, T., 38 Zaitsev, A., 152 Zaitsev, A.B., 152 Zakarian, A., 155, 262 Zanaradi, G., 447 Zang, S.-L., 245 Zani, L., 129 Zanotti-Gerosa, A., 152 Zapf, A., 181, 186, 338 Zard, S.Z., 201 Zarubin, D.N., 11 Zavalij, P., 385 Zawisza, A.M., 349 Zayed, J.M., 263 Zeng, H., 349 Zeng, W., 144, 160 Zeng, X., 401 Zewail, M.A., 203 Zhai, H., 365 Zhang, B., 117 Zhang, C., 358 Zhang, C.-M., 32 Zhang, D., 328, 490 Zhang, G., 227, 270, 365, 375 Zhang, G.-W., 77 Zhang, H., 40, 129, 152, 186, 294, 337, 382 Zhang, H.-L., 152 Zhang, J., 36, 149, 263, 357, 400 Zhang, J.-J., 401 Zhang, J.-M., 123 Zhang, K., 57, 112, 346 Zhang, L., 197, 211, 227, 306, 328, 365, 383 Zhang, M., 189 Zhang, P., 2, 356 Zhang, Q., 312, 382–383, 425, 467 Zhang, Q.-J., 116 Zhang, S., 64, 135, 321, 356, 382, 403 Zhang, T., 17, 40 Zhang, T.Y., 379 Zhang, W., 29, 38, 87, 89, 112, 146, 149, 152, 157, 160, 287, 321, 444 Zhang, W.-Q., 33 Zhang, X., 20, 29, 152–153, 210, 224, 338, 350, 372, 375 Zhang, X.-Q., 152 Zhang, X.P., 143 Zhang, Y., 10, 57, 101, 112, 130, 143, 146, 153, 225, 267, 284, 327, 338, 383, 402 –403, 450, 485

550

Author Index

Zhang, Y.-H., 160 Zhang, Y.J., 149, 160 Zhang, Y.-P., 84, 352 Zhang, Y.-R., 143 Zhang, Z., 152, 213, 440 Zhang, Z.-H., 135 Zhao, B., 28, 181, 187, 434 Zhao, C.-G., 375 Zhao, D., 144, 244 Zhao, F., 346 Zhao, G., 380 Zhao, G.-L., 10, 379– 380 Zhao, H., 83, 444 Zhao, J., 32, 101, 245, 278, 310, 337, 402 Zhao, J.-F., 255, 356, 375 Zhao, K., 269 Zhao, K.-Q., 237, 269 Zhao, L., 356 Zhao, M., 17, 225 Zhao, P., 403 Zhao, Q., 179 Zhao, S.-L., 321 Zhao, W.-X., 116 Zhao, X., 152 Zhao, X.-F., 358 Zhao, Y., 3, 19, 179, 199, 375 Zhao, Y.-J., 255 Zhao, Z.-A., 32 Zhdankin, V.V., 245 Zheglov, S.V., 34, 112 Zheng, B.-H., 28 Zheng, H., 153 Zheng, J., 305 Zheng, L., 21 Zheng, W.-H., 28 Zheng, X., 160 Zheng, X.-J., 26 Zheng, Y., 28 Zheng, Z., 149, 257, 337 Zhizhin, A.A., 11 Zhon, Q.-L., 157 Zhong, J., 32, 116 Zhou, C., 162 Zhou, C.-Y., 117, 222 Zhou, F., 211

Zhou, G., 284 Zhou, H., 117 Zhou, J., 32, 85 Zhou, L., 129, 152, 488 Zhou, M.-D., 245 Zhou, P., 174 Zhou, Q.-L., 32, 117, 152 Zhou, S., 78 Zhou, W., 328 Zhou, X., 22, 269, 403 Zhou, Y., 187, 321, 375 Zhou, Y.-G., 78, 144 Zhou, Z., 112, 130, 187, 327 Zhu, C., 86, 257, 303 Zhu, H.-W., 191 Zhu, J., 61, 117, 123, 263, 289, 447 Zhu, L., 40, 383, 455 Zhu, M., 163 Zhu, M.-K., 173 Zhu, R., 318 Zhu, S., 379 Zhu, S.-F., 32, 117, 157 Zhu, X., 244 Zhu, X.-Y., 123, 401 Zhu, Y., 321 Zhu, Y.-Z., 318 Zhu, Z.-B., 346 Ziang, S.-K., 269 Ziemer, B., 21 Zikos, C., 269 Ziller, J.W., 455 Zimmer, L.E., 297 Zmitek, K., 261 Zolﬁgol, M.A., 411 Zong, L., 21 Zou, G., 84 Zou, H., 485 Zou, J.-P., 287 Zou, Y., 208 Zriba, R., 221, 407 Zu, L., 373, 379, 382 Zuend, S.J., 117 Zulys, A., 272 Zuo, B., 467 Zupan, M., 261 Zweife, T., 45

SUBJECT INDEX Acetalization: (2-hydroxy-5-methoxyphenyl)-diphenylmethanol, 248 indium(III) triﬂate, 258 Acetals, 197 Acetic anhydride, 1 Acetylacetonato(1,5-cyclooctadiene)rhodium(I), 1 Acetylacetonato(dicarbonyl)rhodium(I), 1– 2 Acetyl chloride, 2 Acyl bromides, 205 Acylation: Friedel– Crafts, 6, 81 molybdenum hexacarbonyl, 290 pentaﬂuoroanilinium triﬂate, 351 zinc oxide, 484 C-Acylation: magnesium bromide etherate, 283 samarium(III) chloride, 403 Acyloin condensation, 8– 9 a-Acyloxylation, 369–370 Addition reactions: anti-Markovnikov, 191– 192, 312 1,10 -binaphthalene-2,20 -diol and analogues, 19 1,10 -binaphthalene-2,20 -diol – titanium complexes, 20–21 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 30–31 bis(1,5-cyclooctadiene)rhodium(I) salts, 58 bis[(1,5-cyclooctadiene)hydroxyrhodium], 49–50 bis[chloro(1,5-cyclooctadiene)iridium(I)], 40–41 bis[chloro(1,5-cyclooctadiene)rhodium(I)], 43 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – copper complexes, 66 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – rhodium complexes, 68–69

bis(h3-allyl)dichloropalladium, 37 bis(naphtho[2,1-c])azepines, 76– 77 bismuth(III) triﬂate, 74 boron triﬂuoride etherate, 80 butyllithium, 89 cerium(IV) ammonium nitrate, 98 chromium(II) chloride, 169 cichona alkaloid derivatives, 171–172 copper(I) chloride, 180 copper(I) complexes, 25 copper(I) iodide, 186 copper(I) triﬂate, 188–189 copper(II) triﬂate, 190– 191 dilauroyl peroxide, 201 gold(I) chloride-1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene/silver salts, 212 indium(III) bromide, 255 Grignard reagents, 228– 230 Grignard reagents/chromium(II) salts, 232 Grignard reagents/copper salts, 233 –234 Grignard reagents/iron salts, 235 hydrosilanes, 247 indium, 252– 253 iridium complexes, 264–265 iron(III) chloride, 269 nickel(II) acetylacetonate, 294 organoaluminum reagents, 299 organocopper reagents, 301– 302 organolithium reagents, 305 organozinc reagents, 308 oxygen, 312 palladium(II) acetate – tertiary phosphine, 337 phenyliodine(III) bis(triﬂuoroacetate), 352 –353 platinum and complexes, 359 platinum(II) acetylacetonate, 360 platinum(II) chloride, 360– 361 platinum(II) chloride – silver salts, 365 (S)-proline derivatives, 378 samarium(II) iodide, 403

Reagents for Organic Synthesis, Volume 25. By Tse-Lok Ho Copyright # 2010 John Wiley & Sons, Inc. 551

552

Subject Index

Addition reactions (Continued) tetrakis(triphenylphosphine)platinum(0), 434 triﬂuoromethanesulfonic anhydride, 450 tris(dibenzylideneacetone)dipalladium, 466 zirconocene dichloride, 488–489 Additive aldol reaction, 283–284 Alcoholysis: mandelic acid, 285 samarium(II) iodide, 403 Aldehydes, 22–23 Aldol reactions: aminocarbenes, 8 barium alkoxides, 13 1,10 -binaphthalene-2,20 -diamine derivatives, 14– 15 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – platinum complexes, 68 bis(naphtho[2,1-c])azepines, 75 cobalt(II) acetylacetonate, 174 1,8-diazabicyclo[5.4.0]undec-7-ene, 193 hydrosilanes, 247 potassium t-butoxide, 367– 368 (S)-proline, 370– 372 (S)-proline amides, 373–374 (S)-proline derivatives, 375– 376 (S)-(2-pyrrolidinyl)methylamines, 381 titanocene dichloride –manganese, 441 triﬂuoromethanesulfonic imide, 452 Alkenylation: Friedel– Crafts, 207, 254 indium(III) triﬂate, 258– 259 lithium hexamethyldisilazide, 279 palladium(II) acetate – tertiary phosphine, 333– 334 tris(dibenzylideneacetone)dipalladium, 463– 464 Alkenylsilanes: organolithium reagents, 303 tris(trimethylsilyl)silane, 469 Alkenylzinc reagents, 307– 308 Alkylaluminum chlorides, 3 Alkylation: 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – palladium complexes, 67 Friedel– Crafts, 256, 268 indium(III) bromide, 254 palladium(II) chloride, 342 phase-transfer catalysts, 352

ruthenium(III) chloride, 401 tetrabutylammonium ﬂuoride, 422 triﬂuoromethanesulfonic acid, 450 Alkyl azides, 442 Alkylidenation, 284 S-Alkylisothiouronium salts, 3 Alkyne metathesis, 470 Alkynylation: acetalacetonato(dicarbonyl)rhodium(I), 1 silver ﬂuoride, 411 Allenylidenecyclopropanes, 276 Allylation: h3-allyl(1,5-cyclooctadiene)palladium tetraﬂuoroborate, 3 –4 1,10 -binaphthalene-2,20 -diol – iridium complexes, 20 indium(III) bromide, 254 indium(I) iodide, 257–258 indium(III) triﬂate, 258–259 iron(III) tosylate, 270 palladacycles, 315–316 palladium complexes, 28 platinum and complexes, 359 triruthenium dodecacarbonyl, 460 tris(dibenzylideneacetone)dipalladium, 465 –466 ytterbium(III) triﬂate, 477 zirconyl chloride, 490 h3-Allyl(1,5-cyclooctadiene)palladium tetraﬂuoroborate, 3 –4 h3-Allyl(cyclopentadienyl)palladium, 4 h3-Allyldichloro(triphenylphosphine)palladium, 5 Allylic amination, 324 –325 Allylic oxidation, 310 Allylic substitutions: chiral auxiliaries and catalysts, 108–112 iridium complexes, 25– 26 organozinc reagents, 308 palladium(II) acetate – tertiary phosphine, 335 –336 tetrabutylammonium tricarbonyl(nitroso)ferrate, 423 titanocene dichloride– zinc, 441 tris(dibenzylideneacetone)dipalladium– chloroform, 467 Allystannanes, 5–6 Aluminum bromide, 6 Aluminum chloride, 6– 7 Aluminum dimethylamide, 7

Subject Index

Aluminum iminoxides, 299 Aluminum iodide, 7 Aluminum triﬂate, 8 Aluminum tris(2,6-diphenylphenoxide), 7 –8 Amidation, 79 Amide formation: arylboronic acids, 11 benzensulfonic anhydride, 13 ﬂuorous reagents and ligands, 207 lithium aluminum hydride – selenium, 274 rhodium hydroxide/alumina, 390 tetrabenzyl pyrophosphate, 421 Amides: potassium monoperoxysulfate, 368 titanium(IV) chloride– magnesium, 438–439 p-toluenesulfonyl isocyanate, 442 Amide synthesis: borane sulﬁdes, 79 3-pyridinecarboxylic anhydride, 380 3-pyridinesulfonyl chloride, 380 Amidine synthesis, 185 Amido carbenoids, 482 b-Amido ketones, 483 Amination, 85, 264 Amines: alcohols, butyllithium – (2)-sparteine, 89–90 oxidation of, 357 b-Amino alcohols: erbium(III) triﬂate, 205 indium(III) triﬂate, 258 I-Amino-2-alkanols, methanesulfonic acid, 288 Aminoalkylation: barium alkoxides, 13 tantalum(V) diemthylamide, 421 Aminocarbenes, 8– 10 Aminocarbonylation: nickel(II) acetate, 293 tetrakis(triphenylphosphine)palladium(0), 433 Amino group protection, 203 Aminohydroxylation: 1,10 -binaphthalene-2,20 -diyl phosphites, 33 potassium osmate, 369 I-Aminoindolizines, 418– 419 Aminolysis: 1,10 -binaphthalene-2,20 -diol – niobium complexes, 20 lithium triﬂimide, 281 Annulation: bis[(1,5-cyclooctadiene)hydroxyiridium], 48–49

553

bis[dichloro(pentamethylcyclopentadienyl)iridium(II)], 65 bis[dichloro(pentamethylcyclopentadienyl)rhodium(II)], 66 Antimony(V) chloride, 10 Aromatization: aluminum chloride, 7 tin(IV) chloride, 436 Arylation: bis(h6-arene)dichlororuthenium(II), 39 bis[chloro(1,5-cyclooctadiene)rhodium(I)], 45 bis(dibenzylideneacetone)palladium(0), 60 iron(III) chloride, 267 palladium(II) acetate – tertiary phosphine, 333 –334 palladium(II) chloride – tertiary phosphine, 346 –347 tris(dibenzylideneacetone)dipalladium, 463–464 Arylboronic acids, 11 2-Arylethanols, 303 Aryl ketones and esters, 322 Aryl sulﬁdes, 176 Aryl tetraﬂates, 425 Aryltrialkoxysilanes, 1 Aryne generation, 100–101 Asymmetric hydrogenation, 71–72 Asymmetric Michael reactions, 371 Aza-Baylis-Hillman reaction, chiral auxillaries and catalysts, 129 Aza-Claisen rearrangement, gold(I) triﬂimidetriarylphosphine complex, 227 Aza-Henry reaction, cinchona alkaloid derivatives, 170 Aza-Nazarov coupling, triﬂuoromethanesulfonic acid (triﬂic acid), 449 Aza-transfer, 84 Aza-Wittig reaction triphenylphosphine, 458 Azides: bis(2-methoxyethyl)aminosulfur triﬂuoride, Deoxo-Fluor, 73–74 trimethylsilyl azide, 452–453 Aziridination: diﬂuoro(4-triﬂuoromethylphenyl)bromane, 199 S,S-diphenyl-N-(o-nitrobenzenesulfenyl)N0 -tosylsulfodiimide, 204 hydroxylamine diphenylphosphinate, 247 Azobisisobutyronitrile, 11 Baeyer– Villiger oxidation, 183 Barbier reaction, 251– 252

554

Subject Index

Barium alkoxides, 13 Barium hydride, 13 Bayliss–Hillman reaction: aluminum iodide, 7 aminocarbenes, 8 1,10 -binaphthalene-2-amine-20 phosphines, 14 bismuth(III) triﬂate, 74 cerium(IV) ammonium nitrate, 98 Grignard reagents/copper salts, 233 palladium(II) acetate-phase-transfer catalyst, 327 titanocene dichloride-zinc, 441 Beckmann rearrangement: triphosphazene, 460 zinc chloride, 483 Benzenesulfonic anhydride, 14 1-Benzhydrylamino-2-alkenes, 32 Benzhydryl ethers: diphenyldiazomethane, 203 palladium(II) chloride, 342 Benzothiazoles, 74 O-Benzylation, 13 Benzyl N-phenyl-2,2,2-triﬂuoroacetimidate, 13 Benzyne generation, 424 Biaryls: cobalt(II) bromide, 175 tetrachloroauric acid, 425 Bicyclization, 388 Biginelli reactions, (S)-proline amides, 374 BINAMINE, 15– 17 BINAP: 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – gold complexes, 66 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – iridium complexes, 67 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – rhodium complexes, 68–69 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – ruthenium complexes, 71 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – silver complexes, 72 bis(naphtho[1,2-c])azepine, 76 1,10 -Binaphthalene-2-amine-20 -phosphines, 13 1,10 -Binaphthalene-2-diarylphosphines, 34 1,10 -Binaphthalene-2,20 -bis( p-toluene sulfoxide), 14

1,10 -Binaphthalene-2,20 -diamine derivatives, 14– 15 1,10 -Binaphthalene-2,20 -dicarboxylic acids, 18 1,10 -Binaphthalene-2,20 -diol complexes: copper, 19 iridium, 20 magnesium, 20 niobium, 20 titanium, 20–21 vanadium, 20– 21 1,10 -Binaphthalene-2,20 -diol ethers, 23 1,10 -Binaphthalene-2,20 -diol (modiﬁed) complexes: hafnium, 19 zirconium, 23 zinc, 22–23 1,10 -Binaphthalene-2,20 -diyl N-alkylaminophosphites, 24 1,10 -Binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 29– 32 1,10 -Binaphthalene-2,20 -diyl phosphites, 33 BINOL, 18–22, 27– 30, 33, 132 Bis(acetonitrile)dichloropalladium(II), 34– 36 Bis(h3-allyl)dichloropalladium, 37– 38 Bis(h6-arene)dichlororuthenium(II), 39 Bis(benzonitrile)dichloropalladium(II), 39– 40 Bis[bromotricarbonyl(tetrahydrofuran)rhenium], 40 Bis[chloro(1,5-cyclooctadiene)iridium(I)], 40– 42 Bis[chloro(1,5-cyclooctadiene)rhodium(I)], 43– 45 Bis[chloro(dicyclooctene)rhodium(I)], 46–47 Bis[chloro(diethene)rhodium(I)], 47 Bis[chloro(norbornadiene)rhodium(I)], 47–48 Bis[chloro(pentamethylcyclopentadienenyl)methylthioruthenium] triﬂate, 48 Bis[(1,5-cyclooctadiene)hydroxyiridium], 48– 49 Bis[(1,5-cyclooctadiene)hydroxyrhodium], 49– 50 Bis[(1,5-cyclooctadiene)methoxyiridium(I)], 51 Bis(1,5-cyclooctadiene)nickel(0), 51–57 Bis(1,5-cyclooctadiene)rhodium(I) salts, 57–59 Bis(dibenzylideneacetone)palladium(0), 60–61 Bis[dicarbonylchlororhodium(I)], 61– 64 Bis[dicarbonyl(cyclopentadienyl)iron], 64

Subject Index

Bis[dichloro(1,5-cyclooctadiene) hydridoiridium(II)], 64 Bis[dichloro( p-cymene)ruthenium(II)], 64 Bis[dichloro(pentamethylcyclopentadienyl)iridium(II)], 64– 65 Bis[dichloro(pentamethylcyclopentadienyl)rhodium(II)], 66 [Bis(o-diphenylphosphinobenzylidene)ethanediamine]dichlororuthenium(II), 72–73 2,20 -Bis(diphenylphosphino)-1,10 -binaphthyl and analogues: copper complexes, 66 gold complexes, 66– 67 iridium complexes, 67 palladium complexes, 67–68 platinum complexes, 68 rhodium complexes, 68– 70 ruthenium complexes, 71–72 silver complexes, 72 Bis(ethene)trispyrazolylboratoruthenium, 73 Bis(iodozincio)methane, 73 Bis(2-methoxyethyl)aminosulfur triﬂuoride, 73–74 Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulﬁde, 74 Bismuth(III) sulfate, 74 Bismuth(III) triﬂate, 74– 75 Bis(naphtho[2,1-c])azepines, 75–77 Bis(naphtho[2,1-c])phosphepins, 77 Bis(pentaﬂuorophenyl)[43-dimesitylphosphino2,3,5,6-tetraﬂuorophenyl]borane, 78 1,10 ;3,30 -Bispropanediyl-2,20 -diimidazolylidene, 78 Bis(trialkyphosphine)palladium, 78– 79 Bond insertion, rhodium(II) carboxylates, 386–388 Borane sulﬁdes, 79 Boric acid, 79 Boron tribromide, 79 Boron triﬂuoride etherate, 80–83 Borylation: h3-allyldichloro(triphenylphosphine)palladium, 5 bis[chloro(1,5-cyclooctadiene)iridium(I)], 41–42 bis[(1,5-cyclooctadiene) methoxyiridium(I)], 51 BOX ligands, 119–120, 127, 131, 140, 154, 156, 159 N-bromosuccinimide, NBS, 85

555

Bromination, 485 Bromine, 84 Bromodesilylation, 85 Bromopentacarbonylmanganese, 84 Brook rearrangement, 89, 275, 278, 305, 456 Burgess reagent, 205 t-Butanesulﬁnamide, 85 t-Butyl carbamates, 419 t-Butyl hydroperoxide, 86 t-Butyl hydroperoxide – metal salts, 86– 87 Butyllithium, 88–89 Butyllithium – (2)-sparteine, 89– 90 s-Butyllithium, 90– 91 t-Butyllithium, 91– 92 Calcium bis(hexamethyldisilazide), 95 Carbamates: di-t-butyl dicarbonate, 194 potassium ﬂuoride, 368 Carbamoylation: cobalt– rhodium, 174 trialkylboranes, 443 Carbamoyl azides, 204 Carbenoid insertion, 39 Carbimination, 7 Carboboration, 4 Carbocyclization, 254–255 Carbodiimide formation, 64 Carbonvcarbon bond: cleavage, 262 reduction, 146–149 Carbonvhydrogen bond: functionalization, phenyliodine(III) diacetate –copper salts, 356– 357 insertion, 358 Carbonvnitrogen bond: addition, 123–129 bond reduction, 153 Carbonvoxygen bond: addition, 112–123, 256 bis(1,5-cyclooctadiene)nickel(0), 51–52 cleavage, 429– 430 reduction, 150–152 Carbonylation: bis[chloro(1,5-cyclooctadiene)rhodium(I)], 44– 45 palladium(II) acetate – tertiary phosphine – carbon monoxide, 338–339 tetrachloroauric acid, 425

556

Subject Index

Carbonylation (Continued) meso-tetrakis(4-chlorophenylporphyrinato)aluminum tetracarbonylcobaltate, 425– 426 tributyltin hydride-2,20 -azobis (isobutyronitrile), 446 triphenylsilyl tetracarbonylcobaltate, 460 tris(dibenzylideneacetone)dipalladium, 466 Carbonylative coupling, 418 Carbonyl(chloro)hydridobis(tricyclohexylphosphine) ruthenium, 95 Carbonyl(chloro)hydridotris(triphenylphosphine) rhodium, 95–96 Carbonyldihydridotris(triphenylphosphine)ruthenium, 96 Carboxamides: t-butyl hydroperoxide, 86 lanthanum tris(hexamethyldisilazide), 271 Carboxylation, 339 Carboxyl protection, 297 Catalysis, 120 Cerium(III) chloride, 99 Cerium(IV) ammonium nitrate, 96– 99 Cesium ﬂuoride, 99–101 Chiral auxiliaries and catalysts: allylic substitutions, 108 –112 CvC bond reduction, 146–149 CvN bond addition, 123– 129 CvN bond reduction, 153 CvO bond addition, 112– 123 CvO bond reduction, 150– 152 conjugate additions, 130 –134 coupling reactions, 157 –160 cycloadditions, 135–143 desymmetrization, 102–105, 154 electrophilic substitution, 105–108 epoxidation, 144–146 hydrogenation, 146–153 insertion reactions, 155–157 isomerization, 154 –155 kinetic resolution, 101–102 oxidation reactions, 144–146 rearrangements, 154– 155 o-Chloranil, 160– 161 Chlorination, 163 (Z)-Chloroalkenes, 407– 408 1-Chlorobenzotriazole, 161 Chloro(1,5-cyclooctadiene)-pentamethylcyclopentadienylruthenium-(I), 161–162

Chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium(I), 162 b-Chlorohydrins, 163 1-Chloromethyl-4-ﬂuoro-1,4-diazoniabicyclo [2.2.2]octane bis(tetraﬂuoroborate), 162 m-Chloroperoxybenzoic acid, 163 Chlorotris(triphenylphosphine)cobalt(I), 163 Chlorotris(triphenylphosphine)rhodium(I), 164– 166 Chromium – carbene complexes, 166–169 Chromium(II) chloride, 169 Cichona alkaloid derivatives, 169–173 Claisen condensation, 120 Claisen rearrangement: bis(1,5-cyclooctadiene)rhodium(I) salts, 59 boron triﬂuoride etherate, 81 chiral auxillaries and catalysts, 154–155 tin(IV) chloride, 435 Cleavage: alkenes, 313 –314 multiple CC bonds, t-butyl hydroperoxide – metal salts, 86 tetrakis(triphenylphosphine)palladium(0), 429 –430 2,2,2-trichloroethyl esters, indium, 253 Click reactions, 381 Cobalt, 174 Cobalt(II) acetylacetonate, 174 Cobalt(II) bromide, 175 Cobalt(II) chloride, 175–176 Cobalt(II) iodide/phosphine – zinc, 176 Cobalt– rhodium, 174 Condensation: 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 31– 32 bis[(1,5-cyclooctadiene)-methoxyiridium(I)], 51 hexabutylditin, 241 lithium diisopropylamide, 275–276 organogallium reagents, 302–303 piperidine, 358–359 (S)-proline, 371–372 (S)-proline amides, 374 redox, 156 trimethylsilyl chloride, 453 ytterbium(III) triﬂate, 477, 479 zeolites, 481 Conjugate additions: 1,10 -binaphthalene-2,20 -diamine derivatives, 15

Subject Index

chiral auxiliaries and catalysts, 130– 134 triﬂuoromethanesulfonic anhydride, 450 Copper, 176– 177 Copper(I) bromide, 178– 179 Copper(I) chloride, 180 Copper(I) cyanide, 181 Copper(I) iodide, 183–186 Copper(I) oxide, 187 Copper(I) 2-thienylcarboxynate, 188 Copper(I) triﬂate, 188– 189 Copper(II) acetate, 177– 178 Copper(II) bis(hexaﬂuoroacetylacetonate), 178 Copper(II) bromide, 179 Copper(II) chloride, 181 Copper(II) 2-ethylhexanoate, 182 Copper(II) hexaﬂuroacetylacetonate, 182 Copper(II) nitrate, 187 Copper(II) oxide, 187 Copper(II) triﬂate, 189–191 Copper(II) triﬂuoroacetate, 191 Corey– Chaykovsky reaction, diphenyliodonium triﬂuoroacetate, 202– 203 Coumarin synthesis, 350 Coupling reactions: acetalacetonato(dicarbonyl)rhodium(I), 1– 2 bis(acetonitrile)dichloropalladium(II), 34– 35 bis(h3-allyl)dichloropalladium, 38 bis(benzonitrile)dichloropalladium(II), 39 bis[chloro(dicyclooctene)rhodium(I)], 46 bis[chloro(diethene)rhodium(I)], 47 bis[chloro(norbornadiene)rhodium(I)], 47 bis(1,5-cyclooctadiene)nickel(0), 54– 56 bis(1,5-cyclooctadiene)rhodium(I) salts, 59 bis(dibenzylideneacetone)palladium(0), 60–61 bis[dicarbonylchlororhodium(I)], 61 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – iridium complexes, 67 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – rhodium complexes, 68–70 bis(trialkyphosphine)palladium, 78– 79 bromopentacarbonylmanganese, 84 carbonyldihydridotris(triphenylphosphine)ruthenium, 96 chlorotris(triphenylphosphine)cobalt(I), 163 cobalt, 174 copper, 176–177 copper(I) chloride, 180 copper(I) iodide, 183– 185

557

copper(I) 2-thienylcarboxynate, 188 copper(II) acetate, 177 N,N-diisopropylaminoborane, 200 Grignard reagents/cobalt(II) salts, 232 Grignard reagents/copper salts, 234 Grignard reagents/iron salts, 234– 235 Grignard reagents/manganese salts, 236 Grignard reagents/palladium complexes, 237 Grignard reagents/silver salts, 238 nickel chloride, 295– 296 nickel iodide, 296 nickel(II) acetylacetonate, 294 palladacycles, 315 palladium, 316–317 palladium carbene complexes, 342 palladium/carbon, 318 palladium(II) acetate, 318–320 palladium(II) acetate – copper salts, 323– 324 palladium(II) acetate – imidazol-2-ylidene, 322 palladium(II) acetate – phase-transfer catalyst, 327 palladium(II) acetate – silver salts, 328 palladium(II) acetate – tertiary phosphine, 328 –333 palladium(II) acetylacetonate, 339 palladium(II) bis(triﬂuoroacetate), 340– 341 palladium(II) chloride, 342 –343 palladium(II) chloride – metal salts, 344–345 palladium(II) chloride – tertiary phosphine, 347 –348 palladium(II) iodide, 350 ruthenium(III) chloride, 401 samarium, 403 tetrakis(triphenylphosphine)nickel(0), 426 tetrakis(triphenylphosphine)palladium(0), 426 –428 tris(dibenzylideneacetone)dipalladium, 464 tris(dibenzylideneacetone)dipalladium – chloroform, 468 via C(sp3)-H activation, 334 –335 C-radicals, 195, 447 Cross-coupling: cobalt(II) chloride, 175 –176 (1,3,5-cyclooctatriene)bis(dimethyl fumarate)ruthenium, 192 Cross-metathesis reactions, 395– 397 Cupration, 302 Curtius rearrangement, 319 Cyanation reactions, 454 Cyanomethylation, 452

558

Subject Index

Cyanosilylation, 453 Cyclizations: 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 30–31 bis(1,5-cyclooctadiene)rhodium(I) salts, 59 bis[dichloro(p-cymene)ruthenium(II)], 64 bismuth(III) triﬂate, 74– 75 boron triﬂuoride etherate, 81 copper(II) 2-ethylhexanoate, 182 copper(II) hexaﬂuroacetylacetonate, 182 dichloro(pyridin2–2-carboxylato) gold(III), 197 ﬂuorosulfuric acid – antimony(V) ﬂuoride, 207 gold(I) chloride – tertiary phosphine/silver hexaﬂuoroantimonate-acetonitrile complex, 222 gold(III) chloride, 223 gold(III) chloride – silver triﬂate, 224– 225 hydrogen ﬂuoride – antimony(V) ﬂuoride, 243 hydroxy(tosyloxy)iodobenzene, 248 indium(III) triﬂimide, 260 iron(III) chloride, 268 lanthanum tris(hexamethyldisilazide), 272 methanesulfonic acid, 288 nickel(II) acetylacetonate –diorganozinc, 294 gold(I) chloride – tertiary phosphine/silver salts, 213–220 organoindium reagents, 303 palladium(II) acetate, 321 palladium(II) acetate – copper salts, 322 platinum(II) chloride, 361–363 silver(I) oxide, 413 –414 tetrakis(triphenylphosphine)palladium(0), 430– 433 tin(IV) chloride, 436 titanium(IV) chloride, 437–438 titanium(IV) chloride– zinc, 439 titanocene dichloride –zinc, 441 tributyltin hydride-2,20 -azobis-(isobutyronitrile), 445– 446 tricarbonyl(cyclopentadienyl)-hydridochromium, 447 triﬂuoromethanesulfonic acid, 449– 450 triphenylphosphine, 457–458 tris(acetonitrile)cyclopentadienylruthenium(I) hexaﬂuorophosphate, 461 tungsten hexacarbonyl, 470– 471 zinc iodide, 484

[2þ2þ2]Cycloaddition, 390 Cycloadditions: h3-allyl(cyclopentadienyl)palladium, 4 1,10 -binaphthalene-2,20 -diol – titanium complexes, 21 1,10 -binaphthalene-2,20 -diyl N-alkylaminophosphites, 24 bis[bromotricarbonyl(tetrahydrofuran)rhenium], 40 bis[chloro(norbornadiene)rhodium(I)], 48 bis(1,5-cyclooctadiene)nickel(0), 56–57 bis(1,5-cyclooctadiene)rhodium(I) salts, 59 bis[dicarbonylchlororhodium(I)], 62– 63 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – rhodium complexes, 69 bromopentacarbonylmanganese, 84 chiral auxiliaries and catalysts, 135–143 chloro(1,5-cyclooctadiene) pentamethylcyclopentadienylruthenium(I), 161– 162 chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium(I), 162 chlorotris(triphenylphosphine) rhodium(I), 165 chromium – carbene complexes, 166–169 cichona alkaloid derivatives, 172–173 cobalt– rhodium, 174 cobalt(II) iodide/phosphine – zinc, 176 copper(I) chloride, 180 copper(I) cyanide, 181 copper(I) triﬂate, 188–189 copper(II) triﬂate, 190– 191 copper(II) triﬂuoroacetate, 191 dichloro(diethene)rhodium, 196 dichloro(norbornadiene)bis(triphenylphosphine) ruthenium(II), 197 gold(I) chloride-1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene/silver salts, 212 gold(I) triﬂimide – azolecarbene, 226 iron(III) chloride, 269 nickel bromide– zinc, 295 nickel perchlorate, 296–297 organoaluminum reagents, 300 palladium complexes, 27 platinum(II) chloride, 364 (S)-proline derivatives, 378 rhodium(II) carboxamidates, 385 scandium(III) triﬂate, 409

Subject Index

tetrakis[chloro(pentamethylcyclopentadienyl) ruthenium(I)], 425 tetrakis(triphenylphosphine)palladium(0), 433 trialkylphosphines, 444 triﬂuoromethanesulfonic anhydride, 450– 451 triphenylphosphine, 457–458 triphenylphosphine– dialkyl azodicarboxylate, 459 tris(dibenzylideneacetone)dipalladium, 466 Cyclocarbonylation: Dicobalt octacarbonyl, 198 tetracarbonylhydridocobalt, 424– 425 silver acetate, 411 Cyclocondensation, 456 Cyclodehydation, 287 Cycloelimination, 211 Cycloisomerization: aluminum triﬂate, 8 bis[chloro(1,5-cyclooctadiene)rhodium(I)], 43–44 bis[chloro(dicyclooctene)rhodium(I)], 46 bis[dicarbonylchlororhodium(I)], 63 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – gold complexes, 66 gold(I) chloride – tertiary phosphine, 211 gold(III) oxide, 225 indium(III) triﬂate, 259 lithium diisopropylamide, 276– 277 scandium(III) triﬂate, 410 (1,3,5-Cyclooctatriene)bis(dimethyl fumarate)ruthenium, 192 (1,5-Cycloctadiene)bismethallylruthenium, 191–192 (1,5-Cyclooctadiene)platinum (II) triﬂate, 192 Cyclopentadienyl(h6-naphthalene)ruthenium hexaﬂuorophosphate, 192 Cyclopentadienylyttrium dihydride, 478 Cyclopentenones, 343 Cyclopropanation: chromium(II) chloride, 169 cobalt(II) chloride, 175– 176 lanthanum, 271 lithium hexamethyldisilazide, 280 samarium, 403 silver hexaﬂuoroantimonate, 412 Cycloreversion, 81 Cyclotrimerization, 175 (p-Cymene)(N-tosyl-1,2-diphenylethylenediamine) ruthenium, 192

559

Deacetalization: sodium tetrakis[3,5-bis(triﬂuoromethylphenyl)]borate, 319 water, 475 Deacetylation, 267 Deallylation, 11 De-N-allylation, 390 Debenzylation, 85 Decarbonylation, 44– 45 Decarboxylation: copper(I) oxide, 187 palladium(II) bis(triﬂuoroacetate), 339 Decarboxylative coupling, 462 Deformylation, 368 Dehydration: acetic anhydride, 1 triﬂuoroacetic acid, 448 triphenylphosphine–dialkyl azodicarboxylate, 459 Dehydrochlorination, 351 Dehydrogenation: N-(t-butyl)phenylsulﬁnimidoyl chloride, 92– 93 copper(II) bromide, 179 oxygen, 310 palladium(II) bis(triﬂuoroacetate), 340 platinum and complexes, 359 De-N-methylation, 262 Deoximation, 195 Deoxygenation: copper(I) iodide, 183 magnesium, 283 Deprotonation: butyllithium, 88 lithium diisopropylamide, 277–278 organomagnesium reagents, 306 Derbium(III) triﬂate, 205 Desilylation, 193 Dess-Martin periodinane, 193 De-N-tosylation, 439 2,6-Diacetylpyridine bis-N-(2,6-diisopropylphenyl) imine complex, 266 Dialkyl ﬂuorophosphates, 368 1,4-Diazabicyclo[2.2.2]octane, 193 1,8-Diazabicyclo[5.4.0]undec-7-ene, 193– 194 Diazo group transfer, 251 3,4-Dibromotetrahydropyrans, 254 Di-t-butyl dicarbonate, 194 Dibutyliodotin hydride, 195

560

Subject Index

Dicarbonylhydrido-h5-[1,3-bis(trimethylsilyl)-2hydroxy-4,5,6,7-tetrahydroindenyl]iron, 195 Dichloramine T., 195 Dichlorobis(p-cymene)(triphenylphosphine)ruthenium (II), 196 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, 195–196 Dichloro(diethene)rhodium, 196 Dichloro(norbornadiene)bis(triphenylphosphine)ruthenium(II), 197 Dichloro(pyridine–2-carboxylato) gold(III), 197 Dichlorotris(triphenylphosphine)ruthenium(II), 197 Dicobalt octacarbonyl, 198 Dicyclohexylboron chloride, 198 Diels–Alder reactions: aluminum chloride, 6 arylboronic acids, 11 chiral auxillaries and catalysts, 140– 141 copper(I) 2-thienylcarboxynate, 188 dichlorob(norbornadiene)bis(triphenylphosphine)ruthenium(III), 197 ﬂuorous reagents and ligands, 208 gallium(III) chloride, 209 organoaluminum reagents, 300 (S)-proline, 372 (S)-prolinol derivatives, 378 rutheniuim-carbene complexes, 396 scandium(III) triﬂate, 409 tetrabutylammonium ﬂuoride, 422 triﬂuoromethanesulfonic imide, 452 Di(ethene)trispyrazolylboratoruthenium, 197 Diﬂuoro(4-triﬂuoromethylphenyl)bromane, 199 Dihydroisoquinolines, 415 Dihydrooxazines, 447 Dihydropyran formation, 470 Diiodine pentoxide, 199 (Z)-2,4-Diiodo-2-butenol, 453 1,3-Diiodo-5,5-dimethylhydantoin, 199 Diisobutylaluminum hydride, 199–200 N,N-Diisopropylaminoborane, 200 b-Diketone reactions, 179 Dilauroyl peroxide, 200– 201 Dimanganese decacarbonyl, 201 4-Dimethylaminopyridine, 201 Dimethyldioxirane, 202 Dimethylsulﬁde – halogen, 202 Dimethylsulfoxonium methylide, 202–203

1,1-Dioxonaphtho[1,2-b]thiophene-2-methoxycarbonyl chloride, 203 Diphenyldiazomethane, 203 Diphenyliodonium triﬂuoroacetate, 203 S,S-Diphenyl-N-(o-nitrobenzenesulfenyl)N0 -tosylsulfodiimide, 204 Diphenylphosphonyl azide, 204 Dipyridyliodonium tetraﬂuoroborate, 204 2,3-Disubstituted succinic esters, 307 Dithoacetal cleavage, 310 N,N0 -Ditosylhydrazine, 204 1,4-Diynes, 300 Do¨tz reaction, chromium-carbene complex, 167 Double Michael addition, 284 DuPHOS, 127 Elimination: h3-allyl(cyclopentadienyl)palladium, 4 bis[chloro(1,5-cyclooctadiene)rhodium(I)], 44 butyllithium, 89 Grignard reagents/iron salts, 235 potassium t-butoxide, 367 samarium(II) iodide, 403–404 sodium borohydride– dimethyl ditelluride, 416 tetrabutylammonium ﬂuoride, 422 triﬂuoromethanesulfonic anhydride, 451 Ene reaction, 122, 461 Enolsilylation, 447 Enyne synthesis, 48 Epoxidation 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 32 t-butyl hydroperoxide – metal salts, 86–87 chiral auxiliaries and catalysts, 144–146 dimethyldioxirane, 202 hydrogen peroxide, 244 hydrogen peroxide – metal catalysts, 245 iodosylbenzene, 262 manganese(II) triﬂate, 287 potassium monoperoxysulfate, 368 (S)-proline amides, 375 Epoxides: degradation, sodium periodate, 417 triphenylphosphine–dialkyl azodicarboxylate, 458– 459 Esteriﬁcation: 4-dimethylaminopyridine, 201 1-(p-toluenesufonyl)imidazole, 442

Subject Index

Ether cleavage: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 196 titanium tetraisopropoxide–magnesium, 440 Ethyl(carboxysulfamoyl)triethylammonium hydroxide, 205 Ethyl tribomoacetate, 205 Ferrier rearangement, iron(III) sulfate, 270 Fesulphos ligands, 139 Fluoroboric acid, 207 Fluorohydroxylation, 162 Fluorosulfuric acid – antimony(V) ﬂuoride, 207 Fluorous reagents and ligands, 207–208 Formaldehyde, 208 Formic acid, 208 Fragmentation: hydrogen ﬂuoride, 243 tributyltin hydride-2,20 -azobis-(isobutyronitrile), 446 Fragmentative elimination, 451 Friedel– Crafts acylation: aluminum chloride, 6 indium(III) chloride, 255– 256 Friedel– Crafts alkylation: hafnium(IV) chloride, 241 triﬂuoromethanesulfonic acid, 450 zirconium(IV) chloride, 486 Friedel– Crafts benzylation, 289 Friedel– Crafts reactions: bismuth(III) sulfate, 74 cerium(IV) ammonium nitrate, 98 iodine, 260– 261 iron(III) chloride, 267–268 samarium(III) triﬂate, 407 silica gel, 411 Friedla¨nder reaction, 371 Furans: carbonyldihydridotris(triphenylphosphine)ruthenium, 96 zinc chloride, 483 Gallium(III) chloride, 209 Gem-bishydroperoxides, 99 Glaser coupling: copper, 177 copper(II) acetate, 177 Glycosylation: gold(III) bromide, 210 phenylselenium triﬂate, 358

561

Glycosyl ﬂuorides, 204 Gold, 209–210 Gold(I) chloride: 1,3-bis(2,6-diisopropylphenyl)imidazol-2ylidene/silver salts, 212– 213 gold(I) chloride – tertiary phosphine, 211 gold(I) chloride – tertiary phosphine/silver hexaﬂuoroantimonate-acetonitrile complex, 222 gold(I) chloride – tertiary phosphine/silver salts, 213– 221 Gold(I) cyanide, 225 Gold(I) triﬂimide – azolecarbene, 225– 226 Gold(I) triﬂimide – triarylphosphine complex, 227 Gold(III) bromide, 210 Gold(III) chloride, 223–224 Gold(III) chloride – silver triﬂate, 224– 225 Gold(III) oxide, 225 Graphite, 227 Grignard reagents: addition reactions, 20 cerium(III) chloride, 231 chromium(II) salts, 232 cobalt(II) salts, 232 copper salts, 232–234 iron salts, 234–235 manganese salts, 236 nickel complexes, 236–237 palladium complexes, 237 silver salts, 238 titanium(IV) compounds, 238–239 zirconium compounds, 240 Hafnium(IV) chloride, 241 Halogenation: palladium(II) acetate, 321 tetrabutylammmonium iodide, 423 Halogen/lithium exchange, 280 a-Haloketones, titanocene dichloride– manganese, 441 Heck coupling, 317, 319 Heck reaction: o-alkenoylaryl triﬂates, 157 2,20 -Bis(diphenylphosphino)-1,10 -binaphthyl and analogues – palladium complexes, 67– 68 bis(h3-allyl)dichlorodipalladium, 38 bis(benzonitrile)dichloropalladium(II), 39 bis(dibenzylideneacetone)palladium(0), 60

562

Subject Index

Heck reaction (Continued) cobalt, 174 2,3-dihydrofuran, 157 palladacycles, 315 palladium(II) acetate, 318– 320 palladium(II) acetate – imidazol-2-ylidene, 322 palladium(II) acetate – oxidants, 325 palladium(II) acetate – tertiary phosphine, 329– 330, 332 palladium(II) chloride, 343 palladium(II) chloride - tertiary phosphine, 347 ruthenium–carbene complexes, 399 silica gel, 411 tetrakis(triphenylphosphine)palladium(0), 428, 432 tris(dibenzylideneacetone)dipalladium, 464– 465 Henry reaction: asymmetric, 121 copper(II) triﬂate, 190 palladium(II) hdyroxide/carbon, 349 sodium iodide, 417 triphenylphosphine, 458 Heter-Diels-Alder reaction: 1,10 -binaphthalene-2,20 -diol – magnesium complexes, 20 tin(IV) chloride, 436 Hetero-Diels– Alder reaction: 1,1-binaphthalene-2,20 -diol-titanium complexes, 21 chiral auxillaries and catalysts, 140– 142 cinchona alkaloid derivatives, 173 Heterocycle synthesis: bis(acetonitrile)dichloropalladium(II), 35– 36 tetrakis(triphenylphosphine)palladium(0), 428– 429 zinc triﬂate, 485 Heterocyclization, 447–448 Hetero-Ullmann coupling, 183 Hexabutylditin, 241 Hexaﬂuoroacetone, 242 Hexakis[hydrido(triphenylphosphine)copper], 242 Hexamethylenetetramine, 242 Hiyama coupling: nickel bromide-zinc, 295 tris(trimethylsilyl)silane, 469 Hofmann– Lo¨fﬂer–Freytag reaction, 449 Hofmann rearrangement, 368

Homologation: dicobalt octacarbonyl, 198 organozinc reagents, 308– 309 Homopropargylic alcohols: carbonyl(chloro)hydridotris(triphenylphosphine) rhodium, 95 titanocene bis(triethyl phosphite), 441 zirconocene dichloride, 488 Hydration: bis[(1,5-cyclooctadiene)methoxyiridium(I)], 51 cyclopentadienyl(h6-naphthalene)ruthenium hexaﬂuorophosphate, 192 elimination, 287 Hydrazine hydrate, 242 Hydroalkylation, 200 Hydroamination: 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – gold complexes, 67 bis(ethene)trispyrazolylboratoruthenium, 73 (1,5-cycloctadiene)bismethallylruthenium, 191 –192 (1,5-cyclooctadiene)platinum (II) triﬂate, 192 di(ethene)trispyrazolylboratoruthenium, 197 silver nitrate, 413 titanium tetrakis(diethylamide), 440 zirconium tetrakis(dimethylamide), 486 Hydroarylation, 344 Hydroboration: borane sulﬁdes, 79 rhodium complexes, 29 Hydrochlorination, 242 Hydrodeﬂuorination, 274 Hydrodehalogenation: iridium complexes, 265 palladium(II) chloride – tertiary phosphine, 346 Hydroformylation, 1– 2 Hydrogenation: 1,10 -binaphthalene-2,20 -diyl phosphites, 33 bis(1,5-cyclooctadiene)rhodium(I) salts, 57 2,20 -bis(diphenylphosphino)-1,10 binaphthyl and analogues – iridium complexes, 67 bis[chloro(1,5-cyclooctadiene)rhodium(I)], 43 bis(naphtho[2,1-c])phosphepins, 77 bis(pentaﬂuorophenyl)[43-dimesitylphosphino-2,3,5,6-tetraﬂuorophenyl]borane, 78 chiral auxiliaries and catalysts, 146–153

Subject Index

dicarbonylhydrido-h5-[1,3-bis(trimethylsilyl)2-hydroxy-4,5,6,7-tetrahydroindenyl]iron, 195 gold, 209 –210 palladium, 316 palladium carbene complexes, 342 palladium/carbon, 317–338 palladium(II) hydroxide/carbon, 349 platinum and complexes, 359 rhodium/alumina, 385 rhodium complexes, 28 ruthenium(III) chloride, 401 Hydrogen ﬂuoride, 243 Hydrogen ﬂuoride – antimony(V) ﬂuoride, 243 Hydrogen peroxide: acidic, 244 metal catalysts, 244– 245 Hydrogen transfer: 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 29–30 pentamethylcyclopentadienylbis(vinyltrimethylsilane) cobalt, 351 Hydroiodination, 367 Hydrosilanes, 245–247 Hydrosilylation: hydrosilanes, 247 iron(II) acetate, 266 palladium complexes, 26–27 Hydrostannylation: trialkylboranes, 443 tributyltin hydride, 445 Hydrovinylation, 26 Hydroxyalkylation: 2,20 -bis(diphenylphosphino)-1,10 binaphthyl and analogues – silver complexes, 72 dicyclohexylboron chloride, 198 a-Hydroxyalkyl-g-lactams, 409 Hydroxylamine diphenylphosphinate, 247 o-Hydroxybenzyl ketones, 434 b-Hydroxycarboxamides, 242 (2-Hydroxy-5-methoxyphenyl)diphenylmethanol, 248 Hydroxymethylation: iron(III) nitrate, 269 –270 scandium(III) ﬂuoride, 407 Hydroxy(tosyloxy)iodobenzene, 248 Hydrozirconation, 489–490 Hypervalent iodine reagents, 163 Hypoﬂuorous acid – acetonitrile, 248 –249

563

Imidazole-1-sulfonyl azide hydrochloride, 251 Imido transfer, 11 Imines: 1,10 -binaphthalene-2,20 -dicarboxylic acids, 18 cichona alkaloid derivatives, 170–171 Indanones, 10 1-Indenols, palladium(II) triﬂate, 350 Indium: 1,10 -binaphthalene-2,20 -diol and analogues, 18– 19 Indium(I) iodide, 257– 258 Indium(III) acetate – phenylsilane, 253 Indium(III) bromide, 254 Indium(III) chloride, 255–257 Indium(III) chloride – aluminum, 257 Indium(III) triﬂate, 258–259 Indium(III) triﬂimide, 260 Indoles: indium, 251 synthesis, 283 Indolizines, 366 Insertion: chiral auxiliaries and catalysts, 155–157 by nitrene, gold(III) chloride, 223 pinacolatoboryl azide, 358 silver perchlorate, 414 Iodination: hydrogen peroxide, acidic, 244 iodosuccinimide, 261 –262 tetrabutylammonium dichloroiodate, 421 Iodine, 260–261 Iodosuccinimide, 261–262 Iodosylbenzene, 262 o-Iodoxybenzoic acid, 262– 263 Ionic liquids, 264 Ireland–Claisen rearrangement, 307, 415 Iridium complexes: 1,10 -binaphthalene-2,20 -diyl N-alkylaminophosphites, 25–26 Iron(II) acetate, 266 Iron(II) bromide, 266 Iron(II) chloride, 267 Iron(II) triﬂate, 270 Iron(III) chloride, 267–269 Iron(III) nitrate, 269– 270 Iron(III) perchlorate, 270 Iron(III) sulfate, 270 Iron(III) tosylate, 270 Isoﬂavanones, 225

564

Subject Index

Isomerization: bis(benzonitrile)dichloropalladium(II), 39– 40 2,20 -bis(diphenylphosphino)-1,10 binaphthyl and analogues – rhodium complexes, 68 chiral auxiliaries and catalysts, 154– 155 copper(II) bis(hexaﬂuoroacetylacetonate), 178 copper(II) triﬂate, 189–190 gold(I) chloride, 210–211 Grignard reagents/iron salts, 234 magnesium iodide, 284 methanesulfonic acid, 288 phase-transfer catalysts, 352 platinum(II) chloride, 364–365 rhodium(I) tetraﬂuoroborate, 391 rhodium(II) carboxylates, 389 ruthenium–carbene complexes, 400 silica gel, 410 silver mesylate, 412–413 tris(acetonitrile)cyclopentadienylruthenium(I) hexaﬂuorophosphate, 461 Isothiocyanates: esters, di-t-butyl dicarbonate, 194 p-toluenesulfonyl chloride, 442 Isoxazolidines, 438 b-Keto esters, 289 g-Keto esters, 425 Ketones: Grignard reagents/zirconium compounds, 240 strontium, 419 synthesis, organolithium reagents, 304–305 titanium(IV) chloride– magnesium, 438–439 a-tosyoxylation, 442 triﬂuoroacetic anhydride, 448 Kinetic resolution: 2,20 -bis(diphenylphosphino)-1,10 -binaphthyl and analogues – rhodium complexes, 68 chiral auxiliaries and catalysts, 101– 102 Kulinkovich reaction: cerium(IV) ammonium nitrate, 98 Grignard reagents/titanium(IV)compounds, 238 yttrium(III) chloride, 478 Kumada coupling, 236 –237 b-Lactones, 380 Lanthanum: chloride, 271

triﬂate, 272 tris(hexamethyldisilazide), 271– 272 Lithiation: s-butyllithium, 90 t-butyllithium, 91–92 Lithium aluminum hydride: niobium(IV) chloride, 274 selenium, 274 Lithium borohydride, 274 Lithium chloride, 274 Lithium complexes, 273 Lithium diisopropylamide, 275 –278 Lithium di-t-butylbiphenylide, 275 Lithium hexamethyldisilazide, 278– 280 Lithium – liquid ammonia, 273 Lithium naphthalenide, 280 Lithium 2,2,6,6-tetramethylpiperidide, 280– 281 Lithium triethylborohydride, 281 Lithium triﬂimide, 281 Macrolide synthesis, 7 –8 Magnesiation, 284–285 Magnesium bromide etherate, 283–284 Magnesium iodide, 284 Magnesium perchloride, 284 Magnesium 2,2,6,6-tetramethylpiperidide, 284– 285 Mandelic acid, 285 Manganese, 285 Manganese(II) triﬂate, 287 Manganese(III) acetate, 286– 287 Mannich reactions: 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 30–31 1,10 -binaphthalene-2,20 -diol (modiﬁed) – hafnium complexes, 19 bis[dichloro(1,5-cyclooctadiene) hydridoiridium(II)], 64 chiral auxiliaries and catalysts, 126 lithium chloride, 274 (S)-proline, 371 (S)-proline amides, 374 (S)-proline derivatives, 378 (S)-(2-pyrrolidinyl)azoles, 383 scandium(III) triﬂate, 408 titanium(IV) chloride, 437 zirconia, 485 McMurry coupling: Grignard reagents/iron salts, 235

Subject Index

o-iodoxybenzoic acid, 263 titanium(IV) chloride– zinc, 439 Mercury(II) triﬂate, 287– 288 Mesityltriphenylbismuthonium tetraﬂuoroborate, 288 Metathesis: alkynes, 470 ring closure, 397–399 Methanesulfonic acid, 288 b-Methoxyamino esters, 437 Methylaluminum bis(2,6-di-t-butyl-4methylphenoxide), 289 Methylenation: dimethylsulfoxonium methylide, 202 trimethylsilyldiazomethane, 455 Wittig reagents, 475 Methylene insertion, 203 a-Methylene-g-lactones, indium(III) triﬂate, 258 Michael addition: boron triﬂuoride etherate, 81 zinc triﬂate, 484 Michael– aldol reaction, (S)-prolinol derivatives, 376 Michael– Baylis–Hillman tandem reaction, (S )-prolinol derivatives, 376 Michael-Michael-aldol reaction, (S)-prolinol derivatives, 376 Michael reactions: asymmetric, 372 barium alkoxides, 13 barium hydride, 13 1,10 -binaphthalene-2,20 -bis(p-toluene sulfoxide), 14 1,10 -binaphthalene-2,20 -diol (modiﬁed) – zirconium complexes, 23 bis(1,5-cyclooctadiene)nickel(0), 53 bis(1,5-cycloocatdiene)rhodium(I) salts, 58 bis(naphth[2,1-c])azepines, 76 chiral auxillaries and catalysts, 133 cinchona alkaloid derivatives, 171 –172 1,8-diazabicyclo[5.4.0]undec-7-ene, 193–194 ﬂuoroboric acid, 207 hafnium(IV) chloride, 241 ionic liquids, 264 lithium diisopropylamide, 278 (S)-(2-pyrrolidinyl)azoles, 383 (S)-(2-pyrrolidinyl)methylamines, 381–382 (S)-proline, 372 (S)-proline amides, 374 (S)-proline derivatives, 377– 378

565

scandium(III) triﬂate, 408–409 sodium tetramethoxyborate, 419 1,1,3,3-tetrakis(triﬂuoromethanesulfonyl)propane, 426 tributyltin hydride-2,2N-azobis(isobutyronitrile), 445 triphenylphosphine, 457 tris(dibenzylideneacetone)dipalladium, 464 zinc triﬂate, 484 Mitsunobu reactions: o-(prenyloxymethyl)benzoic acid, 370 triphenylphosphine, 457 triphenylphosphine-dialkyl azodicarboxylate, 458 –459 Mitsunobu reagent, 208 Modiﬁed Claisen condensation, 300 Molybdenum hexacarbonyl, 290–291 Molybdenum(VI) dichloride dioxide, 289 Mukaiyama aldol reaction, 8, 68, 119– 120, 418, 452 Multiple bonds, 15–17, 53– 54, 86 Naﬁon resin, 293 N-Alkenylation, 385 N-Alkoxycarbonylazoles, 2– 3 N-Alkylation: bis[dichloro(p-cymene)ruthenium(II)], 64 triphenylphosphine–dialkyl azodicarboxylate, 459 N-Allylation, 368 N-Arylation: 1,10 -binaphthalene-2,20 -diol – copper complexes, 19 copper(II) oxide, 187 nickel(II) acetylacetonate, 294 (S)-(2-pyrrolidinyl)methylamines, 382 N-Arylsulﬁnylimines, 11 Nazarov cyclization, 31, 82, 143, 189, 266 Nazarov–Friedel– Crafts reaction tandem, 414 N-Bromosuccinimide, 85 N-(t-Butyl)phenylsulﬁnimidoyl chloride, 92–93 N-Chlorosuccinimide, 163 Negishi coupling: bis(benzonitrile)dichloropalladium II, 39 butyllithium, 89 nickel bromide-zinc, 295–296 organozinc reagents, 309 N-Heteroarylation, 443 Nickel, 293 Nickel bromide, 294–295

566

Subject Index

Nickel bromide– zinc, 295 Nickel chloride, 295– 296 Nickel iodide, 296 Nickel perchlorate, 296–297 Nickel(II) acetate, 293 Nickel(II) acetylacetonate, 294 Nickel(II) acetylacetonate –diorganozinc, 294 N-Methyl-2-benzyloxypyridinium triﬂate, 289 Nitration, 473 Nitriles: bis(2-methoxyethyl)aminosulfur triﬂuoride, Deoxo-Fluor, 73– 74 t-butanesulﬁnamide, 85 1,3-diiodo-5,5-dimethylhydantoin, 199 synthesis, sodium dichloroiodate, 417 Nitroaldol reaction, 177– 178 a-Nitrocinnamate esters, 99 2-Nitrophenyl isocyanide, 297 2-Nitro-5-piperidinylbenzyl alcohol, 297 N-Nitrosation, 460 Oppenauer oxidation, 449 Organoaluminum reagents, 299 –300 Organocerium reagents, 300– 301 Organocopper reagents, 301– 302 Organogallium reagents, 302–303 Organoindium reagents, 303 Organolanthanum reagents, 271 Organolithium reagents, 303– 305 Organomagnesium reagents, 306 Organozinc chlorides, 481 Organozincs: additions, 20, 22 reagents, 306– 309 Osmium tetroxide, 310 Osmylation, 310 Overman rearrangement, 154 Oxalic acid, 310 Oxidation: t-butyl hydroperoxide – metal salts, 86 carbonyldihydridotris(triphenylphosphine)ruthenium, 96 cerium(IV) ammonium nitrate, 96–97 chiral auxiliaries and catalysts, 144– 146 m-chloroperoxybenzoic acid, 163 Dess-Martin periodinane, 193 diiodine pentoxide, 199 hydrogen peroxide, 243–244 hypoﬂuorous acid – acetonitrile, 248– 249 o-iodoxybenzoic acid, 263

iron(III) nitrate, 270 manganese(III) acetate, 286 mesityltriphenylbismuthonium tetraﬂuoroborate, 288 oxygen, 310– 311 palladium(II) iodide, 350 phenyliodine(III) bis(triﬂuoroacetate), 353 phenyliodine(III) diacetate – iodine, 357 phenyliodine(III) dichloride, 358 rhodium(II) carboxamidates, 385 ruthenium carbonyl clusters, 402 silver(I) oxide, 413 2,2,6,6-tetramethyl-1-oxopiperidine salts, 435 1,1,1-triﬂuoroacetone, 449 trimethylsilyl chloride, 453 urea – hydrogen peroxide, 473 Oxidative amination, 65 Oxidative cleavage: copper(II) nitrate, 187 palladium (II) acetate – oxidants, 324 phenyliodine(III) bis(triﬂuoroacetate), 353 Oxidative condensation, 199 Oxidative coupling: 1,10 -binaphthalene-2,20 -diol – vanadium complexes, 20– 21 cerium(IV) ammonium nitrate, 98 copper(I) bromide, 178–179 oxygen, 311– 312 rhodium(III) chloride, 390 Oxidative cyclization: azobisisobutyronitrile, 11 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 195 –196 manganese(III) acetate, 286 potassium osmate, 369 Oxidative decarboxylation, 413 Oximes: reduction, 444 triphenylphosphine–dialkyl azodicarboxylate, 459 1-Oxo-4-acetamino-2,2,6,6-tetramethylpiperidinium tetraﬂuoroborate, 310 Oxonew, 368– 369 Oxy-Cope rearrangement, 160 Oxygen, singlet, 312– 313 Oxygenation iron(II) triﬂate, 270 singlet oxygen, 312– 313 tris(trimethylsilyl)silane, 469 –470 Ozone, 313–314

Subject Index

Palladacycles, 315 –316 Palladium–calcium carbonate, 317 Palladium–carbon, 317 –318 Palladium complexes: alumina, 317 1,10 -binaphthalene-2,20 -diyl N-alkylaminophosphites, 26– 27 Palladium(II) acetate: copper salts, 322 –324 imidazol-2-ylidene, 322 oxidants, 324–326 phase-transfer catalyst, 327 silver salts, 328 tertiary phosphine, 328– 337 tertiary phosphine – carbon monoxide, 338– 339 Palladium(II) acetylacetonate, 339 Palladium(II) bis(triﬂuoroacetate), 339–341 Palladium(II) chloride: di-t-butylphosphinous acid, 344 metal salts, 344–346 tertiary phosphine, 346– 349 Palladium(II) hydroxide/carbon, 349 Palladium(II) iodide, 350 Palladium(II) triﬂate, 350 Passerini reaction, 116 Pauson– Khand reaction: bis[chloro(1,5-cyclooctadiene)rhodium(I), 45 bis[dicarbonylchlororhodium(I)], 62–63 chiral auxillaries and catalysts, 142 cobalt–rhodium, 174 dicobalt octacarbonyl, 198 molybdenum hexacarbonyl, 290 palladium(II) chloride – metal salts, 346 Payne rearrangement, 367 Pentaﬂuoroanilinium triﬂate, 351 Pentamethylcyclopentadienylbis(vinyltrimethylsilane)cobalt, 351 Perﬂuorooctanesulfonic acid, 351 Peroxidation, 260 Perrhenic acid, 351 Peterson reaction, organolithium reagents, 303 Phase-transfer catalysts, 351 –352 Ph-BOX ligand, 131 Phenyliodine(III) bis(triﬂuoroacetate), 352– 353 Phenyliodine diacetate: copper salts, 356 –357 iodine, 357 Phenyliodine(III) dichloride, 358 Phenylphosphate, 358 Phenylselenium triﬂate, 358

567

4-Phenyl-1,2,4-triazoline-3,5-dione, 358 Phosphonation, 287 Phosphorylation, 351 Pictet– Spengler reaction: 1,10 -binaphthalene-2,20 -diyl phosphates and 3,30 -diaryl analogues, 31 iodine, 260 perﬂuorooctanesulfonic acid, 351 Pinacol coupling, indium(III) chloride – aluminum, 257 Pinacolatoboryl azide, 358 Piperidine, 358– 359 Platinum and complexes, 359 Platinum(II) acetylacetonate, 360 Platinum(II) chloride: silver salts, 365– 366 Platinum(II) iodide, 366 Poly(methylhydrosiloxane), 366– 367 Polyene synthesis, 440 Polysilanes, 283 Porphyrins, 420 Potassium t-butoxide, 367– 368 Potassium ﬂuoride, 368 Potassium monoperoxysulfate, 368– 369 Potassium osmate, 369 Potassium permanganate, 369– 370 Potassium tetrachloroaurate, 370 o-(Prenyloxymethyl)benzoic acid, 370 Preparations: tellerium chloride, 421 titanium(IV) chloride, 437 (S)-proline, 370 –372 (S)-proline amides, 373– 375 (S)-proline derivatives, 375–379 Pummerer rearrangement, 450, 484 PYBOX ligands, 127, 294 Pyrazoles: Raney nickel, 293 silver hexaﬂuoroantimonate, 412 3-Pyridinecarboxylic anhydride, 380 3-Pyridinesulfonyl chloride, 380 a-Pyrones, 402 Pyrroles, 96 (S)-(2-Pyrrolidinyl)azoles, 383 (S)-(2-Pyrrolidinyl)methylamines, 381– 382 4-Pyrrolidinopyridine, 380 Quinoline synthesis: gold(I) chloride-1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene/silver salts, 212

568

Subject Index

Quinoline synthesis (Continued) gold(III) chloride, 224 Quinones, 369 o-Quinones, 263 Radical additions: indium(III) acetate – phenylsilane, 253 magnesium bromide etherate, 284 Radical cyclizations: dilauroyl peroxide, 200 1,10 -binaphthalene-2,20 -diol (modiﬁed) – zinc complexes, 23 manganese(III) acetate, 286 tricarbonyl(cyclopentadienyl)hydridochromium, 447 Raney nickel, 293 RCM, 439 Rearrangements: alkylaluminum chlorides, 3 bismuth(III) triﬂate, 74 boron tribromide, 79–80 boron triﬂuoride etherate, 82–83 s-butyllithium, 91 chiral auxiliaries and catalysts, 154– 155 chlorotris(triphenylphosphine)rhodium(I), 165– 166 copper(II) chloride, 181 1,4-diazabicyclo[2.2.2]octane, 193 diisobutylaluminum hydride, 199 4-dimethylaminopyridine, 201 gold(I) chloride-1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene/silver salts, 212 gold(I) chloride – tertiary phosphine/silver salts, 220–221 gold(I) triﬂimide – azolecarbene, 225–226 gold(I) triﬂimide – triarylphosphine complex, 227 iridium complexes, 26 methylaluminum bis(2,6-di-t-butyl-4-methylphenoxide), 289 phenyliodine(III) bis(triﬂuoroacetate), 353 titanium(IV) chloride, 437 tris(dibenzylideneacetone)-dipalladium, 466 tris(dibenzylideneacetone)dipalladium– chloroform, 469 Redox cyclization, 41 Redox reactions: 1,10 -binaphthalene-2,20 -diamine derivatives, 17 calcium bis(hexamethyldisilazide), 95 iron(II) chloride, 267 (S)-proline derivatives, 378– 379

Reductions: acetalacetonato(dicarbonyl)rhodium(I), 2 bis[(1,5-cyclooctadiene)hydroxyrhodium], 49 [bis(o-diphenylphosphinobenzylidene)ethanediamine]dichlororuthenium(II), 72– 73 1,10 ;3,30 -bispropanediyl-2,20 -diimidazolylidene, 78 borane sulﬁdes, 79 t-butyllithium, 92 cerium(III) chloride, 99 (p-cymene)(N-tosyl-1,2-diphenylethylenediamine) ruthenium, 192 diisobutylaluminum hydride, 199 N,N-diisopropylaminoborane, 200 hydrosilanes, 245–246 indium(III) acetate – phenylsilane, 253 indium(III) chloride – aluminum, 257 lithium triethylborohydride, 281 nickel, 293 organoaluminum reagents, 300 palladium(II) acetate – tertiary phosphine, 336 –337 samarium, 403 samarium(II) iodide, 404–406 sodium borohydride, 416 sodium iodide, 417 sulfur, 420 trialkylboranes, 443 trialkylphosphines, 444 triﬂuoromethanesulfonic anhydride, 450 zinc, 481– 482 Reductive acylation: chlorotris(triphenylphosphine)rhodium(I), 164 magnesium, 283 Reductive addition, 404 Reductive aldol reaction, 294 Reductive alkylation, 482 Reductive amination, 274 Reductive cleavage: lithium – liquid ammonia, 273 molybdenum hexacarbonyl, 291 Reductive coupling: Grignard reagents/titanium(IV) compounds, 238 –239 lithium, 273 nickel bromide– zinc, 295 zirconocene, 487 Reductive cyclization, 441 Reductive lithiation, 275 Reductive phenylation, 6

Subject Index

Reductive silylation: chlorotris(triphenylphosphine)rhodium(I), 164– 165 zinc chloride, 483 Reformatsky reaction: chlorotris(triphenylphosphine)-rhodium(I), 164 1,10 -binaphthalene-2,20 -diol (modiﬁed) – zinc complexes, 23 magnesium, 283 titanocene dichloride-manganese, 441 Retro-Claisen reaction, 259 Rhenium carbonyl clusters, 385 Rhodium complexes: alumina, 385 1,10 -binaphthalene-2,20 -diyl N-alkylaminophosphites, 28– 29 hydroxide/alumina, 390 Rhodium(I) tetraﬂuoroborate, 391 Rhodium(II) carboxamidates, 385 Rhodium(II) carboxylates, 386 –389 Rhodium(III) chloride, 390 Rhodium(III) iodide, 391 Ring cleavage: phenyliodine(III) diacetate – iodine, 357 scandium(III) triﬂate, 407 Ring contraction, 248 Ring expansion: hexakis[hydrido(triphenylphosphine)copper], 242 methylaluminum bis(2,6-di-t-butyl-4-methylphenoxide), 289 palladium(II) chloride-metal salts, 345 Ritter reaction, zinc chloride, 483 Ruthenium –carbene complexes, 391–400 Ruthenium carbonyl clusters, 402 Ruthenium oxide–sodium periodate, 402 Ruthenium(III) chloride, 401 Sakurai reaction, hafnium(IV) chloride, 241 Samarium, 403 Samarium(II) iodide, 403–406 Samarium(III) chloride, 403 Samarium(III) triﬂate, 407 Sandmeyer reaction, 417 Scandium(III) ﬂuoride, 407 Scandium(III) triﬂate, 407–410 Schiff reaction, copper(I) iodide, 185 Schmidt rearrangement, boron triﬂuoride etherate, 81 SEGPHOS ligand, 127, 138, 350

569

Selectcﬂuorw, 162 Shapiro reaction, tris(dibenzylideneacetone)dipalladium, 464 Silica gel, 410– 411 Silver acetate, 411 Silver ﬂuoride, 411 Silver hexaﬂuoroantimonate, 412 Silver mesylate, 412– 413 Silver nitrate, 413 Silver perchlorate, 414 Silver tetraﬂuoroborate, 414 Silver triﬂate, 415 Silver(I) oxide, 413– 414 Silylation, 484 O-Silylation: bis[chloro(dicyclooctene)rhodium(I)], 47 triethylsilyl chloride, 448 Silylboration, 34 Silyl transfer, 415 Simmons-Smith reaction, asymmetric, 135 Sn-W mixed hydroxide, 437 Sodium borohydride complexes, dimethyl ditelluride, 416 Sodium dichloroiodate, 417 Sodium hydride, 417 Sodium iodide, 417 Sodium nitrite, 417 Sodium periodate, 417 Sodium phenoxide, 418 Sodium tetracarbonylferrate(II), 418 Sodium tetrachloroaurate, 418 Sodium tetrakis[3,5-bis(triﬂuoromethylphenyl)]borate, 319 Sodium tetramethoxyborate, 419 Sonogashira coupling: copper, 176 ﬂuorous reagents and ligands, 208 gold(I) chloride – tertiary phosphine, 211 palladium(II) acetate – tertiary phosphine, 329 palladium(II) chloride – metal salts, 344 palladium(II) chloride–tertiary phosphine, 348 silica gel, 411 tetrakis(triphenylphosphine)palladium(0), 427 Staudinger reaction, triphenylphosphine, 457 Stille coupling: bis(acetonitrile)dichloropalladium(II), 34 dibutyliodotin hydride, 195 nickel bromide– zinc, 295 palladium/calcium carbonate, 317

570

Subject Index

Strecker reaction: cinchona alkaloid derivatives, 171 rhodium(III) iodide, 391 trimethylsilyl cyanide, 454 Strecker synthesis, 18 Strontium, 419 Sulfamic acid, 419 Sulfonyl azides, 161 Sulfur, 420 Sulfuric acid, 420 Suzuki coupling: bis(acetonitrile)dichloropalladium(II), 34 bis(h3-allyl)dichlorodipalladium, 38 bis[(1,5-cycloocatdiene)hydroxyrhodium], 50 palladium/alumina, 317 palladium/carbon, 318 palladium(II) acetate, 318– 319 palladium(II) acetate-imidazol-2-ylidene, 322 palladium(II) acetate – tertiary phosphine, 329 palladium carbene complexes, 342 palladium(II) chloride, 342– 343 palladium(II) chloride – tertiary phosphine, 347 tetrakis(triphenylphosphine)palladium(0), 426– 427 tris(dibenzylideneacetone)dipalladium, 462–463 tris(dibenzylideneacetone)dipalladiumchloroform, 467 TADDOL ligands, 102, 112, 119, 122, 159 Tandem cyclization, 279 Tandem reactions, 399– 400 Tantalum(V) diemthylamide, 421 Tellerium chloride, 421 Tetrabenzyl pyrophosphate, 421 Tetrabutylammonium dichloroiodate, 421 Tetrabutylammonium ﬂuoride, 422–423 Tetrabutylammmonium iodide, 423 Tetrabuytlammonium phenolate, 423 Tetrabutylammonium tricarbonyl(nitroso)ferrate, 423–424 Tetrabutylammonium triphenyldiﬂuorosilicate, 424 Tetracarbonylhydridocobalt, 424–425 Tetrachloroauric acid, 425 1,1,2,2-Tetraﬂuoroethanesulfonyl chloride, 425 Tetrakis[chloro(pentamethylcyclopentadienyl)ruthenium(I)], 425 meso-Tetrakis(4-chlorophenylporphyrinato)aluminum tetracarbonylcobaltate, 425 Tetrakis(triethylphosphate)nickel(0), 426

1,1,3,3-Tetrakis(triﬂuoromethanesulfonyl)propane, 426 Tetrakis(triphenylphosphine)nickel(0), 426 Tetrakis(triphenylphosphine)palladium(0), 426– 433 Tetrakis(triphenylphosphine)platinum(0), 434 Tetramethylammonium ﬂuoride, 434 2,2,6,6-Tetramethyl-1-oxopiperidine salts, 435 Thiobenzylation, 160– 161 Thionation, 435 Thiophosphoryl chloride, 435 Tin(IV) chloride, 435–437 Titanium tetraisopropoxide–magnesium, 440 Titanium tetrakis(diethylamide), 440 Titanium(III) chloride, 437 Titanium(IV) chloride complexes: magnesium, 438– 439 Mischmetal, 439 zinc, 439 Titanocene bis(triethyl phosphite), 440– 441 Titanocene dichloride complexes: manganese, 431 zinc, 441 p-Toluenesulfonic complexes: anhydride, 442 chloride, 442 ﬂuoride, 442 isocyanate, 442 isocyanate, N-tosyl amides, 442 1-(p-Toluenesulfonyl)imidazole, 442 O-(p-Toluenesulfonyl)-Nmethylhdyroxylamine, 442 Tosylation: indium, 251 p-toluenesulfonyl chloride, 442 N-Tosylindolines, 287– 288 Transacylation, 99 Transalkoxylation, 270 Transamination, 7 Transesteriﬁcation: hexamethylenetetramine, 242 4-pyrrolidinopyridine, 380 scandium(III) triﬂate, 410 tetrabutylammonium tricarbonyl(nitroso)ferrate, 424 Transfer hydrogenation, 284 Transylidation, 386 Trialkylboranes, 443 2,8,9-Trialkyl-1-phospha-2,5,8,9tetraazabicylco[3.3.3]undecanes, 443

Subject Index

Trialkylphosphines, 444 1,2,3-Triazoles, 455 Triazole synthesis, 181 Tributyltin hydride, 445 Tributyltin hydride-2,20 -azobis(isobutyronitrile), 445–446 Tricarbonyl(cyclopentadienyl)hydridochromium, 447 Trichloroacetonitrile, 447 Trichlorosilane, 447 Triethyl phosphite, 447– 448 Triethylsilyl chloride, 448 Triﬂuoroacetic acid, 448 Triﬂuoroacetic anhydride, 448 1,1,1-Triﬂuoroacetone, 449 1,1,1-Triﬂuoroalkanes, 243 2,2,2-Triﬂuoroethyl isocyanate, 449 Triﬂuoromethanesulfonic acid, 449– 450 Triﬂuoromethanesulfonic anhydride, 450–451 Triﬂuoromethanesulfonic imide, 452 Triﬂuoromethylation: chlorotris(triphenylphosphine)-rhodium(I),64 Triﬂuoromethyl ketones, 448 Triﬂuoromethyltrimethylsilane, 452 Trimethylsilylacetonitrile, 452 Trimethylsilyl azide, 452– 453 Trimethylsilyl chloride, 453 Trimethylsilyl cyanide, 454 Trimethylsilyldiazomethane, 455 Trimethylsilyl triﬂuoromethanesulfonate, 455–456 Triphenylphosphate– bromine, 460 Triphenylphosphine, 456–458 Triphenylphosphine–dialkyl azodicarboxylate, 458–459 Triphenylsilyl tetracarbonylcobaltate, 460 Triphosphazene, 460 Triruthenium dodecacarbonyl, 460 Tris(acetonitrile)cyclopentadienylruthenium(I) hexaﬂuorophosphate, 461 Tris(dibenzylideneacetone)dipalladium, chloroform, 467– 469 Tris(pentaﬂuorophenyl)borane, 469 Tris(trimethylsilyl)silane, 469–470 Tritylation, 469 Tungsten carbene/carbyne complexes, 470 Tungsten hexacarbonyl, 470–471 Ugi reaction: 2-nitrophenyl isocyanide, 297 phenylphosphate, 358

Ullmann coupling: copper(I) bromide, 179 copper(I) iodide, 183 Ullmann diaryl ether synthesis, 17, 183, 374 Urea – hydrogen peroxide, 473 Urea nitrate, 473 Vinylation, 367 Vinyl ethers and esters, 213 Von Braun degradation, 84 Wacker oxidation, 35, 312, 346 Wagner–Meerwein rearrangement, 466 Water, 475 Williamson synthesis, 417 Wittig reaction: butyllithium, 88 dimethylsulﬁde – halogen, 202 trichlorosilane, 447 Wittig reagents, 67, 127, 475 Wittig rearrangement, 154, 182, 279 Wolff –Kishner reduction, 242 X/Li exchange: butyllithium, 88 t-butyllithium, 91 X/magnesium exchange, 228 Ytterbium(III) triﬂate, 477 Yttrium(III) chloride, 478 Yttrium(III) triﬂate, 479 Zeolites, 481 Zinc, 481–483 Zincation, 306 Zinc bromide, 483 Zinc chloride, 483 Zinc iodide, 484 Zinc oxide, 484 Zinc triﬂate, 484–485 Zirconia, 485 Zirconium tetrakis(dimethylamide), 486 Zirconium(IV) bromide, 485 Zirconium(IV) t-butoxide, 486 Zirconium(IV) chloride, 486 Zirconocene, 487 Zirconocene dichloride, 488– 489 Zirconocene hydrochloride, 489–490 Zirconyl chloride, 490

571