wiley-vch...further stimulate both the development and applications of this enormously useful and...

Metal-catalyzed Cross-coupling Reactions

Edited by Francois Diederich and Peter J. Stang

8 WILEY-VCH Weinheim - Berlin - New York . Chichester - Brisbane Singapore - Toronto

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8 WILEYmVCH


Edited by Francois Diederich and Peter J. Stang

8 WILEY-VCH Weinheim - Berlin - New York . Chichester - Brisbane Singapore - Toronto

Prof. Dr. Frangois Diederich Laboratorium fu r Organische Chcmie Eidgenijssische Technische Hochschule ETH-Zentrum. Universitatstrasse 16 CH-8092 Zurich, Switzerland USA

Prof. Dr. Peter J. Stang Department of Chemistry University of Utah Salt Lake City, UT 841 12

This book was carefully produced. Nevertheless, the authors, editors and, publisher d o not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements. data, illustrations, procedural details or other items may inadvertently be inaccurate.

Copyright 0 1998 by Wiley-VCH Verlag GmbH Pappelallee 3, D-69469 Weinheim. Germany Nurioiru/O6201-6060 Internririonu/(+49) 6201 6060

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Library of Congress Cataloging-in-Publication Data Diederich, FranGois

Peter J. Stang. Metal catalyzed cross-coupling reactions I FranGois Diederich,

p. cm. Includes bibliographical references and index.

1. Organic compounds-Synthesis. 2. Metal Catalysts. I. Stang, Peter J. 11. Title. QD262.D53 1997 547’. 1 3 9 3 4 ~ 2 1 97-13417

ISBN 3-527-29421 -X

CIP Deutsche Biblwthek Cataloging-in-Publication Data: A catalogue record for this book is available from the Deutsche Bibliothek

British Library Cafaloging in Public&-on Data: A catalogue record for this book is available from the British Library

ISBN 3-527-2942 I -X

Typeset by Mackreth Media Services, Hemel Hempstead, Herts Printed and bound in Great Britain by Bookcraft (Bath) Ltd This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production.

Dedicated to the memory of Professor John K. Stille,

one of the pioneers of modern cross-coupling reactions

Foreword

Carbon-carbon bond-forming reactions are arguably the most important processes in chemistry, as they represent key steps in the building of more complex molecules from simple precursors. In the past 50-100 years, organic chemists have developed a plethora of reactions for carbon-carbon bond formation between molecules with saturated sp3 C-atoms. However, until the discovery and development of metal-mediated cross-coupling reactions, starting in the 1970s, there were no simple, general direct methodologies known for carbon- carbon bond formation between unsaturated species such as vinyl, aryl, and alkynyl moieties. In other words, carbon-carbon bond formation between sp and sp2 C-atom centers was often difficult and tedious. In the intervening 25 years, a wide variety of cross-coupling methodologies have been developed and cross-coupling reactions have emerged among the most powerful and useful synthetic tools in chemistry.

Metal-catalyzed cross-coupling reactions are extensively employed in a wide range of areas of preparative organic chemistry, from the synthesis of complex natural products to supramolecular chemistry and materials science. For example, the formation of new carbon- rich polymers and networks by acetylenic molecular scaffolding, the development of many abiotic receptors, and the preparation of many dendrimers depends heavily on modern cross-coupling methodologies. In fact, in the 1990s one can hardly open a chemical journal in the broad area of organic chemistry or materials science that does not contain several examples of cross-coupling reactions.

Many of the metal-mediated cross-coupling reactions discussed in this book follow a similar mechanistic scheme. The general features of the catalytic cycles are currently quite well understood and involve an oxidative addition-transmetallation-reductive elimination sequence. The reaction is initiated by the oxidative addition of the electrophile to the zero- valent metal. The most widely used active catalysts are diverse Ni(0) and Pd(0) complexes with organic triflates or halides (mostly iodides or bromides; rarely chlorides) as the electrophilic partners. A wide variety of organometallic reagents (organo-boron-aluminum, -copper, -zirconium, -silicon, -tin, etc.) serve as nucleophiles. However, the details of the individual steps, and in particular the transmetallation process, are less well understood and the reaction pathways are highly dependent upon the specific organometallic nucleophiles as well as reaction conditions.

In this multi-authored monograph, a dozen experts and leaders in the field bring the reader Up to date by documenting and critically analyzing current developments and uses of metal-catalyzed cross-coupling reactions. The various methodologies involving organosilicon, -copper, -tin, -zinc, -zirconium, -aluminum, and -boron reagents, as well as the diverse uses of 1 P-additions to 1,3-dienes, carbometallations, and carbonylations, in natural Product synthesis are covered. Emphasis is placed upon key developments and important advances, which are illustrated with attractive and useful examples. Carefully chosen references guide the reader through the extensive literature in the field. A particularly attractive and useful feature, that enhances the practical value of this monograph, i h the

... Vl l l Foreword

inclusion of key synthetic protocols, in experimental format, chosen for broad utility and application.

We anticipate that this monograph will be of value to both expert and novice practitioners in the area of metal-catalyzed cross-coupling reactions. We hope that it will further stimulate both the development and applications of this enormously useful and already widely employed reactivity principle in all fields of chemistry involving synthesis depending upon carbon-carbon bond formation.

ETH Ziirich Salt Lake City, Utah February 1997

FranGois Diederich Peter J . Stang

List of Contributors

Prof. Jan-E. Biickvall Department of Organic Chemistry University of Uppsala, Box 531 751 21 Uppsala Sweden

Prof. Tamejiro Hiyama Tokyo Institute of Technology Research Laboratory of Resources Utilization 4259 Nagatsuta, Midori-ku, Yokohama, Kanagawa 227 Japan

Prof. Paul Knochel Fachbereich Chemie der Philips-Universitat Hans-Meerwein-Strasse 35043 Marburg Germany

Prof. Armin de Meijere Institut fir Organische Chemie der Universitiit Gottingen Tammannstrasse 2 37077 Wttingen Germany

Prof. Terence N. Mitchell Universitiit Dortmund Fachbereich Chemie Otto-Hahn-Str. 6 44221 Dortmund Germany

Prof. Jean-F. Normant Laboratoire de Chimie des Organoklkments associC au CNRS

Universitt P. et M. Curie 4, Place Jussieux 7523 1 Paris Ctdex 05 France

TOW 44-45

Prof. Larry E. Overman Department of Chemistry University of California Irvine, California 92697-2025 USA

Prof. Kenkichi Sonogashira Department of Applied Science and Chemistry Fukui University of Technology 3-6-1 Gakuen, Fukni 910 Japan

Prof. Akira Suzuki Department of Chemical Technology Kurashiki University of Science and the Arts Tsura-jima, Kurashiki-shi 7 12 Japan

Prof. Jiro Tsuji Department of Applied Chemistry Okayama University of Science Ridai-cho, Okayama 700 Japan

h f . Ei-ichi Negishi Department of Chemistry &due University West Lafayette, Indiana 47907 USA

Contents

1

1.1

1.2 1.2.1

1.2.2 1.2.2.1

1.2.2.2

1.2.2.3 1.2.3

1.2.4 1.2.4.1

1.2.4.2 1.2.5 1.2.5.1 1.2.5.2 1.2.5.3

1.2.6 1.2.7

1.3

1.4

1.5

1.6

Palladium- or Nickel-catalyzed Cross-coupling with Organometals Containing Zinc. Magnesium. Aluminum. and Zirconium

Ei-ichi Negishi. Fang Liu

Introduction . . . . . . . . . . . . . . . . . . . . . . . . Systematic survey of palladium- or nickel-catalyzed cross-coupling . . Scope with respect to metal counterions and inhibition of catalysis by organolithiums . . . . . . . . . . . . . . . . . . . . . . .

Palladium-catalyzed cross-coupling involving alkynylmetals and related alkynyl nucleophiles: alkynyl.ary1. alkynyLalkeny1. and alkynyl-alkynyl

Hydrometallation cross-coupling and carbometallation - cross-coupling tandem protocols and other alkenyl.ary1. alkenyl.alkeny1. and alkenyl-

Aryl-aryl coupling . . . . . . . . . . . . . . . . . . . . . . Palladium-catalyzed cross-coupling involving alkyl groups without proximal unsaturation. . . . . . . . . . . . . . . . . . . . .

Coupling reactions of alkenyl- and arylmetals with allyl. benzyl. and propargyl electrophiles . . . . . . . . . . . . . . . . . . . . Cross-coupling with allyl- and benzylmetals . . . . . . . . . . . .

Cross-coupling between two unsaturated carbon groups . . . . . . .

coupling . . . . . . . . . . . . . . . . . . . . . . . . . .

alkynyl coupling reactions: double metal catalysis . . . . . . . . .

Cross-coupling involving allyl. benzyl. and propargyl groups . . . . .

Cross-coupling involving carbonyl compounds . . . . . . . . . . . Palladium-catalyzed acylation of organometals with acyl halides . . . . Palladium-catalyzed allylation and related reactions of enolates . . . . a-Substitution of carbonyl compounds with unsaturated carbon groups . . . . . . . . . . . . . . . . . Leaving groups . . . . . . . . . . . . . . . . . . . . . . . Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . Assymetric cross-coupling . . . . . . . . . . . . . . . . . . .

Palladium-catalyzed tandem processes involving cross-coupling reactions . . . . . . . . . . . . . . . . . . . . . . . . . . Mechanism of cross-coupling . . . . . . . . . . . . . . . . .

Conclusions . . . . . . . . . . . . . . . . . . . . . . . .

1

4

4 6

6

7 10

12 16

16 18 18 18 19

21 24 26

27

30

34

37

xii Contents

I . 7 Representative experimental procedures . . 1.7.1 p.Methoxyphenylethyne . . . . . . . . . 1.7.1.1 Preparation of ethynylzinc chloride . . . . 1.7.1.2 Preparation of p-methoxyphenylethyne . . . 1.7.2 (7E.9E. 11E.13E) .Retino1 (vitamin A) . . . 1.7.3 a-Farnesene . . . . . . . . . . . . . 1.7.4 (a -1 -[ l'-methyl-(E)-2'-heptenylidene]indan

Abbreviations . . . . . . . . . . . . . References . . . . . . . . . . . . . .

. . . . . . . . . . . 39

. . . . . . . . . . . 39

. . . . . . . . . . . 39

. . . . . . . . . . . 39

. . . . . . . . . . . 40

. . . . . . . . . . . 41

. . . . . . . . . . . 41

. . . . . . . . . . . 42

. . . . . . . . . . . 42

2

2.1

2.2 2.2.1 2.2.2 2.2.3 2.2.4

2.3

2.3.1 2.3.2

2.4 2.4.1 2.4.2 2.4.3 2.4.4 2.4.5

2.5

2.6 2.6.1

2.6.1.1 2.6.1.2 2.6.2

2.6.3

2.6.3.1 2.6.3.2

Cross-coupling Reactions of Organoboron Compounds with Organic Halides

Akira Suzuki

Introduction . . . . . . . . . . . . . . . . . . . . . . . .

Preparation of organoboron compounds . . . . . . . . . . . . . Hydroboration of alkenes and alkynes . . . . . . . . . . . . . . Haloboration of terminal alkynes . . . . . . . . . . . . . . . . Preparation from organolithium and magnesium reagents . . . . . . Miscellaneous methods . . . . . . . . . . . . . . . . . . . .

Palladium-catalyzed reactions of organoboron compounds and their mechanism . . . . . . . . . . . . . . . . . . . . . . . . . Cross-coupling reactions . . . . . . . . . . . . . . . . . . . Other reactions catalyzed by transition-metal complexes . . . . . . .

Cross-couplingreactionsoforganoboroncompounds . . . . . . . . Coupling of 1 -alkenylboron derivatives: Synthesis of conjugated dienes . Coupling of arylboron compounds: Synthesis of biaryls . . . . . . . Coupling of alkyboron derivatives . . . . . . . . . . . . . . . . Reactions with triflates . . . . . . . . . . . . . . . . . . . . Carbonylative coupling . . . . . . . . . . . . . . . . . . . .

Conclusions . . . . . . . . . . . . . . . . . . . . . . . . Experimental procedures . . . . . . . . . . . . . . . . . . . Reaction of I-alkenylboronates with vinylic halides: Synthesis of (lZ,3E) . 1 -phenyl- 1. 3-octadiene . . . . . . . . . . . . . . . . (E)- 1 -Hexenyl- 1.3, 2-benzodioxaborole . . . . . . . . . . . . . . (1Z. 3 0 - l.Phenyl.1. 3.octadiene . . . . . . . . . . . . . . . . Reaction of arylboronic acids with haloarenes: synthesis of sterically

Reaction of 9-alkyl-9-borabicyclo[3.3. llnonane with 1-bromo- 1- phenylthioethene: synthesis of 4-(3-cyclohexenyl)-2-phenylthio- 1 -butene 1 -Bromo- 1-phenylthioethene . . . . . . . . . . . . . . . . . . 9-[2-(3-Cyclohexenyl)ethyl]-9-BBN . . . . . . . . . . . . . . .

hindered biaryls . . . . . . . . . . . . . . . . . . . . . . .

49

49 49 51 52 53

54 54 61

63 63 70 74 79 81

82

84

84 84 85

85

86 86 86

... Contents XI11

2.6.3.3 4-(3-Cyclohexenyl)-3-phenylethio- I-butene . . . . . . . . . . . .

2.6.4.1 2-Allyl-2-carbomethoxycyclo-7-heptenyl triflate . . . . . . . . . . 2.6.4.2 2,3.Trimethylene.3.carbomethoxycyclo. 7.heptene . . . . . . . . .

2.6.4 Intramolecular cross-coupling of enol triflates with organoboron compounds: Synthesis of 2,3.trimethylene. 3.carbomethoxycycloheptene

2.6.5 Carbonylative coupling reaction: Synthesis of (Q-5-pentadecen-7-one . Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . .

3

3 . I

3.2 3.2.1 3.2.2 3.2.3 3.2.4 3.2.5 3.2.6

3.3 3.3.1 3.3.2 3.3.3

3.3.3.1 3.3.3.2 3.3.4 3.3.5 3.3.6 3.3.7 3.3.8 3.3.9

3.4

3.5

3.6

3.7

3.8 3.8.1 3.8.2

Palladium-catalyzed Coupling of Organyl Halides to Alkenes . The Heck Reaction

Stefan Brase. Armin de Meijere

Introduction . . . . . . . . . . . . . . . . . . . . . . . .

Principles . . . . . . . . . . . . . . . . . . . . . . . . . The mechanism . . . . . . . . . . . . . . . . . . . . . . . The catalysts . . . . . . . . . . . . . . . . . . . . . . . . The alkenes . . . . . . . . . . . . . . . . . . . . . . . . .

The leaving groups . . . . . . . . . . . . . . . . . . . . . .

Cascade reactions and multiple couplings . . . . . . . . . . . . . Heck cascades involving sp2 centers . . . . . . . . . . . . . . .

Cascades consisting of Heck and subsequent cycloaddition or electrocyclization reactions . . . . . . . . . . . . . . . . . . Heck and Diels-Alder cascades . . . . . . . . . . . . . . . . . Heck 6n-electrocyclization cascades . . . . . . . . . . . . . . .

Effects of bases. ligands. and additives . . . . . . . . . . . . . .

Stereochemical requirements in intramolecular cyclizations . . . . . .

Heck-reactioncascades involving ~p~andspcenters . . . . . . . . .

Heckcombined with othercross-coupling processes . . . . . . . . Palladium-catalyzed reactions with nucleophilic substrates . . . . . . Heck-aldol and Heck-Michael cascades . . . . . . . . . . . . . C -H activation in Heck-type processes . . . . . . . . . . . . . Heck with consecutive carbonylation reactions . . . . . . . . . . . Multiple Heck couplings . . . . . . . . . . . . . . . . . . . Related palladium-catalyzed reactions . . . . . . . . . . . . . . Enantioselective Heck-type reactions . . . . . . . . . . . . . . Syntheses of natural products and biologically active compounds . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . .

Experimental procedures . . . . . . . . . . . . . . . . . . . Dipotassium (Q.4.4'.diphenylstilbene.4''.4"'.disulfonate (stilbene I) . . trans-4-Acety lstilbene . . . . . . . . . . . . . . . . . . . .

87

88 88 88 88 89 89

99

99 99

101 102 105 107 112

114 115 116

117 117 118 121 122 126 127 130 130

133

134

139

141

148 148 149

xiv Contents

3.8.3

3.8.4 Diethyl4'-chloro-4'-methoxycarbonylspiro[cyclopropane- 1.3 '-

Methyl 3-(E)-( 2-[2-(E)-methoxycarbonylethenyl]cyclopent- 1 -enyl] acrylate. . . . . . . . . . . . . . . . . . . . . . . . . . 150

bicyclo[4.3.0]non-l'(6')-ene]-8',8'-dicarboxylate . . . . . . . . . 150 3.8.5 (R).2.Cyclohexenyl.2, 5.dhydrofwan . . . . . . . . . . . . . . 151 3.8.6 Methoxy.l.(S).ethenyl.l,2,3, 4.tetrahydronaphthalene . . . . . . . . 151

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . 152 Abbreviations and acronyms . . . . . . . . . . . . . . . . . . 152 References . . . . . . . . . . . . . . . . . . . . . . . . . 154

4 Organotin Reagents in Cross-Coupling

Terence N . Mitchell 4.1

4.2 4.2.1 4.2.1.1 4.2.1.2 4.2.1.3 4.2.2 4.2.3 4.2.4 4.2.5

4.3 4.3.1 4.3.2 4.3.3 4.3.4

4.4 4.4.1 4.4.2

4.5

4.6

Introduction . . . . . . . . . . . . . . . . . . . . . . . . 167

Stille coupling of alkenyltins . . . . . . . . . . . . . . . . . . Intermolecular reactions . . . . . . . . . . . . . . . . . . . . 168 Reactions involving organic halides and triflates . . . . . . . . . . Reactions involving acid chlorides . . . . . . . . . . . . . . . 170 Reactions involving ally1 carbonates . . . . . . . . . . . . . . . Intramolecular reactions . . . . . . . . . . . . . . . . . . . . 172 Reactions of distannylalkenes . . . . . . . . . . . . . . . . . 173 Less conventional reactions . . . . . . . . . . . . . . . . . . 175 Mechanistic considerations and the choice of catalyst . . . . . . . .

Stannylfurans. -thiophenes, and -pyrroles . . . . . . . . . . . . . Stannylpyridines (and -quinolines) . . . . . . . . . . . . . . . 180 Stannylindoles . . . . . . . . . . . . . . . . . . . . . . . 182 Other heterocycles . . . . . . . . . . . . . . . . . . . . . . 182

Reactions of aryltins . . . . . . . . . . . . . . . . . . . . . 182 Reactions with triflates . . . . . . . . . . . . . . . . . . . . 182 Reactions with halides . . . . . . . . . . . . . . . . . . . . 183 Reactions of alkynyltins . . . . . . . . . . . . . . . . . . . . 185

Reactions of alkyltins . . . . . . . . . . . . . . . . . . . . . 187

167

168

171

178

179 179

Reactions of substrates where tin is attached to a heterocyclic ring . . .

4.7 Reactionsinvolvingvarious typesof tetraorganotin . . . . . . . . . 187

4.8 Reactions of allyl.. allenyl.. and propargyltins . . . . . . . . . . . 188 4.9 Related palladium-catalyzed reactions . . . . . . . . . . . . . . 189 4.9.1 Reactions of ditins (and silylstannanes) . . . . . . . . . . . . . . 189 4.9.1.1 Cross-coupling reactions . . . . . . . . . . . . . . . . . . . 190 4.9.1.2 Addition reactions . . . . . . . . . . . . . . . . . . . . . . 190 4.9.2 Reactions of tin hydrides . . . . . . . . . . . . . . . . . . . 190 4.9.3 Reactions of tin alkoxides. thioalkoxides. and stannylamines . . . . . 192

Contents xv

4.10

4.1 1

4.12

4.13 4.13.1 4.13.2 4.13.3 4.13.4

5

5.1

5.2 5.2.1 5.2.2

5.3 5.3.1 5.3.2 5.3.3 5.3.4 5.3.5 5.3.5.1 5.3.5.2 5.3.5.3 5.3.5.6

5.4

5.5 5.5.1 5.5.2 5.5.3 5.5.4 5.5.5 5.5.6 5.5.7 5.5.8

Reactions induced by copper . . . . . . . . . . . . . . . . . . Nickel-catalyzed reactions . . . . . . . . . . . . . . . . . . . 193

Mechanistic discussion and conclusion . . . . . . . . . . . . . . Experimental procedures . . . . . . . . . . . . . . . . . . . 195 Indanomycin . . . . . . . . . . . . . . . . . . . . . . . . N. N ‘-Bis(trifluoromethanesu1fonyl)papuamine . . . . . . . . . . . 196 Rapamycin . . . . . . . . . . . . . . . . . . . . . . . . . Anickel-catalyzedprocedure: 1-Phenylpent-4-en-1-yne . . . . . . . 196 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . 197

192

194

195

196

References . . . . . . . . . . . . . . . . . . . . . . . . . 197

Cross-coupling Reactions to sp Carbon Atoms

Kenkichi Sonogashira

Introduction . . . . . . . . . . . . . . . . . . . . . . . . 203

Alkynylcopper reagents . . . . . . . . . . . . . . . . . . . . 203 Alkynylborane reagents . . . . . . . . . . . . . . . . . . . . 205 Transition-metal-catalyzed Cross-coupling . . . . . . . . . . . . 206 Alkynylzinc reagents . . . . . . . . . . . . . . . . . . . . . 206 Alkynyltin reagents . . . . . . . . . . . . . . . . . . . . . 208 Alkynylmagnesium reagents . . . . . . . . . . . . . . . . . . 211 Alkynylborane reagents . . . . . . . . . . . . . . . . . . . . 212 Terminal acetylene with sp2- carbon halides . . . . . . . . . . . . Synthesis of internal acetylenes . . . . . . . . . . . . . . . . . Synthesis of terminal acetylenes . . . . . . . . . . . . . . . . 216 Stereospecific synthesis . . . . . . . . . . . . . . . . . . . . 220 Cross-coupling of haloalkynes with organometallic compounds . . . . 222 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . 223 Experimental procedures . . . . . . . . . . . . . . . . . . . 224 Undeca-3.5-diy n- 1-01 . . . . . . . . . . . . . . . . . . . . . 224 Alk-35diyn- 1-01 . . . . . . . . . . . . . . . . . . . . . . 224 Q-5-Undecen-3-yn- 1-01 . . . . . . . . . . . . . . . . . . . 224 Diphenylacetylene . . . . . . . . . . . . . . . . . . . . . . 225 4-Phenylbut- 1 -en-3-yne . . . . . . . . . . . . . . . . . . . . 225 p-Nitroethynylbenzene . . . . . . . . . . . . . . . . . . . . 226 (73-7-Pentadecen-5,9-y n- 1-01 . . . . . . . . . . . . . . . . . 226 Terminal acetylene by potassium-hydroxide-catalyzed retro-Favorsky reaction . . . . . . . . . . . . . . . . . . . . . . . . . . 226 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . 227 References . . . . . . . . . . . . . . . . . . . . . . . . . 227

Cross-coupling reactions of alkynylmetal reagents with sp2 carbon atoms .. 203

213 213

xvi Contents

6 Intramolecular Heck Reactions in Natural Product Chemistry

J . T . Link. Larry E . Overman 6.1 introduction . . . . . . . . . . . . . . . . . . . . . . . . 231

6.2 Mechanistic outline . . . . . . . . . . . . . . . . . . . . .

6.3.1 Five-membered rings . . . . . . . . . . . . . . . . . . . . . 233 6.3.2 Six-membered rings . . . . . . . . . . . . . . . . . . . . . 236 6.3.3 Seven-membered rings . . . . . . . . . . . . . . . . . . . . 242 6.3.4 Eight-membered rings . . . . . . . . . . . . . . . . . . . . 243 6.3.5 Largerings . . . . . . . . . . . . . . . . . . . . . . . . . 244

6.4 Cycloisomerization of enynes . . . . . . . . . . . . . . . . . 246

6.5 Tandem reactions . . . . . . . . . . . . . . . . . . . . . . 248

6.6 Asymmetric reactions . . . . . . . . . . . . . . . . . . . . . 256

6.7 Concluding comments . . . . . . . . . . . . . . . . . . . . 260 6.8 Representative experimental procedures . . . . . . . . . . . . . 6.8.1 General comments about catalysts. reagents. and conditions . . . . . 6.8.2 [7a.8a 1-Dispiro[ 1.3.dioxolane.2. 1 ’.~yclohex.2’.ene.4’.8~ ’.

7” [ (methox ycarbony 1)aminometh y 11 [ 5H- 1. 31 diox o [ 4. 5 -g] [ 21 benzop y ran1 6.8.3 (-).5.6.Dehydr0.17.[10. 1 l.dihydro.5H.dibenzo[a.dlcyclohepten.5.y~ 1.

6.8.4 (SP, 17~)[email protected])oxymethyl.5.19.methylenedioxyandrosta n.

6.8.5 (2R*.4aS*.7S*.9aS*).2.Hydroxy.4.(4.hydroxybutyl).7.methyl.1,2.5.6.7.

6.8.6

4- benzyloxy-3-methoxymorphinan . . . . . . . . . . . . . . .

1, 8( 14), 9( 1 I)-triene

9a.hexahydro.4a,7.methano.4aH .benzocycloheptene . . . . . . . . (S)-3-Formylmethyl- 1,2.dihydro.5.methox y. 1,3.dimethyl.2.0~ o. [3H]indole . . . . . . . . . . . . . . . . . . . . . . . . . Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . .

261 261

263

263

263

264

265 266 266

7 Carbometallation Reactions

Ilane Marek. Jean F . Normant

7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 271

7.2 Carbometallation of alkynes . . . . . . . . . . . . . . . . . . 271 7.2.1 Intermolecular carbometallation . . . . . . . . . . . . . . . . 271 7.2.2 Intramolecular carbometallation . . . . . . . . . . . . . . . . 276 7.2.2.1 Five-membered ring synthesis . . . . . . . . . . . . . . . . . 276 7.2.2.2 Four-membered ring synthesis . . . . . . . . . . . . . . . . . 282 7.2.2.3 Six-membered ring synthesis . . . . . . . . . . . . . . . . . . 282

Contents xvii

7.3 7.3.1 7.3.2

7.4 7.4.1 7.4.2

7.5 7.5.1 7.5.1.1 7.5.1.2 7.5.1.3

7.5.1.4 7.5.1.5 7.5.2

7.6

7.7

7.8 7.8.1 7.8.2 7.8.3 7.8.4 7.8.5

8

8.1

8.2 8.2.1 8.2.1.1 8.2.1.2 8.2.1.3 8.2.1.4 8.2.1.5 8.2.1.6 8.2.1.7 8.2.2 8.2.2.1

Carbometallation of allenes . . . . . . . . . . . . . . . . . . Intramolecular carbometallation . . . . . . . . . . . . . . . . Intermolecular carbometallation . . . . . . . . . . . . . . . . Carbometallation of conjugated enynes . . . . . . . . . . . . . . Intermolecular carbometallation . . . . . . . . . . . . . . . . Intramolecular carbolithiation of conjugated silylated enynes . . . . .

Carbometallation of alkenes . . . . . . . . . . . . . . . . . . Intramolecular carbometallation . . . . . . . . . . . . . . . . Five-membered ring synthesis . . . . . . . . . . . . . . . . . Six-membered ring synthesis . . . . . . . . . . . . . . . . . . Four-membered ring synthesis and rearrangements of bis(homoally1) metals . . . . . . . . . . . . . . . . . . . . . . . . . . . Three-membered ring synthesis . . . . . . . . . . . . . . . . . Five-membered ring synthesis via cyclization of vinyllithium derivatives Intermolecular carbometallation . . . . . . . . . . . . . . . . Enantioselective carbometallation of alkenes . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . Experimental procedures . . . . . . . . . . . . . . . . . . . (E)-l-Chloro-2-allyl-3-tert-butoxy)hex- I-ene . . . . . . . . . . . General procedure for the cyclization involving Rieke’s activated zinc . Typical procedure for the cyclization of propargylic organozinc reagents anfi-(3S*.4R*).Dimethylno n- 1 -ene . . . . . . . . . . . . . . . (S)-ZBenzylhexan- 1-01 . . . . . . . . . . . . . . . . . . . . Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . References and notes . . . . . . . . . . . . . . . . . . . . .

Palladium-catalyzed 1. 4.Additions to Conjugated Dienes

Jan.E . Backvall Introduction . . . . . . . . . . . . . . . . . . . . . . . . Palladium(0)-catalyzed reactions . . . . . . . . . . . . . . . . Addition of H-Nu . . . . . . . . . . . . . . . . . . . . . . 1. 4.Hydrosilylation . . . . . . . . . . . . . . . . . . . . . 1. 4Hydrostannation . . . . . . . . . . . . . . . . . . . . . 1 . 4.Hydroamination . . . . . . . . . . . . . . . . . . . . . Addition of active methylene compounds . . . . . . . . . . . . . 1. 4.Hydrosulfonation . . . . . . . . . . . . . . . . . . . . . 1 . CHydroboration . . . . . . . . . . . . . . . . . . . . . . 1. 4.Hydrocyanation . . . . . . . . . . . . . . . . . . . . . 1PCoupling with R- and Nu . . . . . . . . . . . . . . . . . 1. 4.Carboamination . . . . . . . . . . . . . . . . . . . . .

283 283 286

287 287 287

289 290 290 304

305 306 306 307

322

328

329 329 330 330 331 331 331 332

339

339 340 340 342 342 343 344 344 345 345 346

xviii Contents

8.2.2.2 8.2.2.3 8.2.2.4

8.3 8.3. I 8.3.1.1 8.3.1.2 8.3.1.3 8.3.1.4 8.3.1.5

8.4 8.4.1 8.4.2 8.4.3

8.4.4

9

9.1 9.1.1

9.2

9.3 9.3.1 9.3.2 9.3.3 9.3.4

9.4 9.4.1 9.4.1.1 9.4.1.2 9.4.1.3 9.4.1.4

9.4.2 9.4.2.1

I . 4.Addition of R (aryl or vinyl) and stabilized carbanions . . . . . 1 . 4.Addition of carbon and oxygen nucleophiles . . . . . . . . . . 1.4.Carbosilylation . . . . . . . . . . . . . . . . . . . . . .

Palladium(I1)-catalyzed reactions . . . . . . . . . . . . . . . . 1. 4.Addition of two nucleophiles . . . . . . . . . . . . . . . . 1. 4.Diacyloxylation . . . . . . . . . . . . . . . . . . . . . 1. 4.Haloacyloxylation . . . . . . . . . . . . . . . . . . . . I. 4.Addition of an alkoxide and another oxygen function or a halide . . 1. 4.Oxyamination and 1. 4.chloroamination . . . . . . . . . . . . Intramolecular 1. Cadditions with C-C bond formation . . . . . . .

Experimental Procedures . . . . . . . . . . . . . . . . . . . (3aS*.5R*.7aR*).5.Acetoxy.2.0~0.2.3.3a.4.5.7 a.hexahydrobenzo.uran . cis-4-Chloro-3-[4-(benzyloxy)butyl~-2-cyclohexen- 1 -yl acetate . . . . (3&*.5S*.7aR* ). 1 -(Benzyloxycarbonyl)-5-chloro-2,3.3a.4,5,7a- hexahydroindole . . . . . . . . . . . . . . . . . . . . . . . ( 1 S*.4S*.6R*).4.Chloro.7. 7.di( methoxycarbony1)-9- methylenebicyclo[4.4.0]dec-2-ene. . . . . . . . . . . . . . . . Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . References and notes . . . . . . . . . . . . . . . . . . . . .

Carbon-Carbon Bond Formation Reactions Mediated by Organozinc Reagents

Paul Knochel

Introduction . . . . . . . . . . . . . . . . . . . . . . . . Methods of preparation of zinc organometallics . . . . . . . . . .

Uncatalyzed cross-coupling reactions . . . . . . . . . . . . . .

Copper-catalyzed cross-coupling reactions . . . . . . . . . . . . Cross-coupling reactions with allylic halides and related reactive halides Cross-coupling reactions with alkynyl. alkenyl. and aryl halides . . . . Cross-coupling reactions with alkyl halides . . . . . . . . . . . . Acylation reactions . . . . . . . . . . . . . . . . . . . . . .

Transition-metal-catalyzed cross-coupling reactions . . . . . . . . . Palladium and nickel-catalyzed C - bond formation reactions . . . . . Addition to unactivated double bonds . . . . . . . . . . . . . . Addition to unactivated triple bonds: nickel-catalyzed carbozincation . . Catalytic Cqp3-CSp3 cross-coupling reactions . . . . . . . . . . . . Palladium-catalyzed cross-coupling between polyfunctional unsaturated substrates . . . . . . . . . . . . . . . . . . . . . . . . . Cobalt.. manganese.. and iron-catalyzed cross-coupling reactions . . . Carbonylations and acylations . . . . . . . . . . . . . . . . .

337 349 350

359 352 353 363 372 376 377

3x0 380 380

381

381 381 382

387 388

391

393 393 396 398 398

399 399 399 403 403

406 407 407

Contents xix

9.4.2.2 9.4.2.3

9.5

9.6 9.6.1 9.6.2 9.6.3 9.6.4 9.6.5 9.6.6 9.6.7 9.6.8 9.6.9 9.6.10 9.6.1 1 9. 6.12 9.6.13 9.6.14 9.16.15 9.6.16 9.6.17

10

10.1

10.1.1 10.1.2 10.1.3

10.2 10.2.1 10.2.2 10.2.3 10.2.4 10.2.5

10.3 10.3.1 10.3.2 10.3.3

Cobalt-catalyzed cross-coupling reactions . . . . . . . . . . . . . 408 Manganese- and copper-catalyzed radical cyclizations . . . . . . . . 409

Conclusions . . . . . . . . . . . . . . . . . . . . . . . . 410

Experimental procedures . . . . . . . . . . . . . . . . . . . 410 Q.6.Chloro.2.hexenenitnle . . . . . . . . . . . . . . . . . . 410

Quinidine derivative 21 . . . . . . . . . . . . . . . . . . . . 411 6-Chloro-l-cyclohexenyl- l-hexyne . . . . . . . . . . . . . . . 411

(E).lO.Pivaloxy.5.decenenitrile . . . . . . . . . . . . . . . . . 412 10-Nitro-9-phenyldecyl acetate . . . . . . . . . . . . . . . . . 412 2, 5.Dibenzoylthiophene . . . . . . . . . . . . . . . . . . . . 413 l-Butyl-l-(3-nitro-2-phenylpropyl)cyclopentane . . . . . . . . . . 413 Ethyl 12-acetoxy-2-dodecanoate . . . . . . . . . . . . . . . . 414

4-Chlorobiphenyl . . . . . . . . . . . . . . . . . . . . . . 414

Di(4-chlorobutyl) ketone . . . . . . . . . . . . . . . . . . . 415 5-Oxododecyl Pivalate . . . . . . . . . . . . . . . . . . . . 416 cis-Bicyclo[4.3.0]nonan-l-ol . . . . . . . . . . . . . . . . . . 416 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . 416 References . . . . . . . . . . . . . . . . . . . . . . . . . 416

(3-Myrtany1)cyclopentanone . . . . . . . . . . . . . . . . . . 410

3-(4-Pentynyl)-2-cyclohexen- l-one . . . . . . . . . . . . . . . 412

(E)-4-(5-Chloro-l-pentenyl)benzonitrile . . . . . . . . . . . . . 414

(4’.Chloro.3.trifluoromethanesulfonyloxy)biphenyl . . . . . . . . . 414 4”.Cyano.4.methoxy.l, 1 ’,2’, 1“-terphenyl . . . . . . . . . . . . . 415

Organosilicon Compounds in Cross-coupling Reactions

Tamejiro Hiyama

Introduction . . . . . . . . . . . . . . . . . . . . . . . . 421

A brief history of the cross-coupling reaction . . . . . . . . . . . 421

Activation of a C - Si bond by a nucleophile . . . . . . . . . . . 422 Coupling reactions of alkenylsilanes . . . . . . . . . . . . . . . 423 Trimethyl(viny1)silane . . . . . . . . . . . . . . . . . . . . 423 Alkenylsilanes . . . . . . . . . . . . . . . . . . . . . . . 424 Stereochemistry . . . . . . . . . . . . . . . . . . . . . . . 425 Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . 426 Synthetic applications . . . . . . . . . . . . . . . . . . . . 428

Coupling reactions of arylsilanes . . . . . . . . . . . . . . . . 429 Prototype of biaryl synthesis . . . . . . . . . . . . . . . . . . 429 Coupling with chlorobenzene . . . . . . . . . . . . . . . . . . 432 Use of sodium hydroxide activator . . . . . . . . . . . . . . . 432

Previous studies on organosilicon-based cross-coupling reactions . . . 421

xx Contents

10.3.4 10.3.5 10.3.6

10.4 10.4.1 10.4.2

10.5

10.6 10.6. I 10.6.2 10.6.3 10.6.4

10.7 10.7.1 10.7.2 10.7.3

10.8 10.8.1 10.8.2

10.9 10.9.1 10.9.2 10.9.3

10.10 10.10.1 10.10.2

10.10.3 10.10.4

Applications . . . . . . . . . . . . . . . . . . . . . . . . 432 Carbonylative coupling . . . . . . . . . . . . . . . . . . . . 433 Mechanism. . . . . . . . . . . . . . . . . . . . . . . . . 434

Coupling reactions of alkynylsilanes . . . . . . . . . . . . . . . Synthesis of conjugated acetylenes . . . . . . . . . . . . . . . 435 Three-component coupling reaction . . . . . . . . . . . . . . . 436

Coupling reactions of disilanes . . . . . . . . . . . . . . . . .

Coupling reactions of alkylsilanes . . . . . . . . . . . . . . . . Methylation . . . . . . . . . . . . . . . . . . . . . . . . 436 Alkylation . . . . . . . . . . . . . . . . . . . . . . . . . 437

435

436

436

Leaving groups of the coupling partner . . . . . . . . . . . . . . 437 Stereochemistry . . . . . . . . . . . . . . . . . . . . . . . 439

440 Coupling reactions of allylsilanes . . . . . . . . . . . . . . . . Regiochemistry . . . . . . . . . . . . . . . . . . . . . . . 440 Stereochemistry . . . . . . . . . . . . . . . . . . . . . . . 442 Asymmetric chemistry . . . . . . . . . . . . . . . . . . . . 444

Coupling reactions without fluoride ion . . . . . . . . . . . . . . Coupling reactions of allylic carbonates . . . . . . . . . . . . . 446 Coupling reactions of diene monoxides . . . . . . . . . . . . . .

Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . 448 Availability of organosilicon reagents . . . . . . . . . . . . . . The future of the organosilicon-based cross-coupling reaction . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . 449

Experimental procedures . . . . . . . . . . . . . . . . . . . 449 1 -Vinylnaphthalene . . . . . . . . . . . . . . . . . . . . . 449

3,5.isopropylidenedioxy. 6.heptenoate . . . . . . . . . . . . . . 450 4-Fluoro-4’-methoxy- 1, 1 ’-biphenyl . . . . . . . . . . . . . . . 450 3,4.Difluoro.4’.(frans.4.propylcyclohexyl ). I , 1 ’-biphenyl . . . . . . 451 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . 451 References . . . . . . . . . . . . . . . . . . . . . . . . . 452

446

448

448 449

tert.Butyl(3R,5S,6E).7.[2.Cyclopropyl.4(4.fluorophenyl)quinolin.3.y~ 1.

11 Palladium-catalyzed Coupling Reactions of Propargylic Compounds

Jiro Tsuji. Tadakatsu Mandai

11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 455

11.2 Classification of palladium-catalyzed reactions based on mechanistic considerations . . . . . . . . . . . . . . . . . . . . . . . . 455

Contents xxi

11.3

11.3.1 11.3.2 11.3.2.1 11.3.2.2

11.3.2.3 11.3.2.4 11.3.2.5 11.3.2.6 11.3.2.7

11.3.2.8 11.3.2.9 11.3.2.10

11.4

11.4.1 11.4.2

11.5

11.5.1 11.5.2

11.6 11.6.1 11.6.2 11.6.3 11.6.4

Reactions via insertion into the sp2 carbon bond of allenylpalladium intermediates (Type I) . . . . . . . . . . . . . . . . . . Reactions of alkenes: formation of 1.2.4.alkatrienes . . . . . . . Carbonylation . . . . . . . . . . . . . . . . . . . . . . Reaction features . . . . . . . . . . . . . . . . . . . . Preparation of 2. 3.alkadienoates and their derivatives by monocarbonylation . . . . . . . . . . . . . . . . . . . . Preparation of triesters by dicarbonylation Dicarbonylation of propargyl chloride and alcohols . . . . . . .

. . . . . . . . . .

Preparation of a-alkenylidene-y-lactones . . . . . . . . . . . Preparation of a-alkenylidene-/%lactams . . . . . . . . . . . Carbonylation in the presence of active methylene and methyne

Dominocarbonylation andDiels-Alderreaction . . . . . . . . Domino carbonylation and ene reaction . . . . . . . . . . . . Preparation of cyclopentenonecarboxylates . . . . . . . . . .

compounds . . . . . . . . . . . . . . . . . . . . . . .

. . 459

. . 459

. . 459

. . 459

. . 461

. . 463

. . 466

. . 468

. . 469

. . 469

. . 470

. . 471

. . 473 Reactions via transmetallation of allenylpalladium intermediates and related reactions (Type 11) . . . . . . . . . . . . . . . . . . . Reactions of hard carbon nucleophiles . . . . . . . . . . . . . .

Reactions via attack by soft carbon and 0x0 nucleophiles on the central 479

Reactions of soft carbon nucleophiles . . . . . . . . . . . . . . 479 Reaction of 0x0 nucleophiles . . . . . . . . . . . . . . . . . . 484

Experimental procedures . . . . . . . . . . . . . . . . . . . 485 Reaction of carbonate with alkenes . . . . . . . . . . . . . . . 485 Domino carbonylation and Diels-Alder reaction . . . . . . . . . . 486 Reaction with alkyne . . . . . . . . . . . . . . . . . . . . . 487 Furan formation by the reaction with acetoacetate . . . . . . . . . 487 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . 487 Reference . . . . . . . . . . . . . . . . . . . . . . . . . 489

475 475 477 Reaction of terminal alkynes: formation of 1,2.alkadien. 4.ynes . . . .

carbonof allenylpalladium intermediates (Type 111) . . . . . . . . .

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 Subjectlndex 495 . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 Palladium- or Nickel-catalyzed Cross- coupling with Organometals Containing Zinc, Magnesium, Aluminum, and Zirconium

Ei-ichi Negishi, Fang Liu

1.1 Introduction

The cross-coupling reaction of organometallic reagents with organic halides and related electrophiles represents one of the most straightforward methods for carbon-carbon bond formation (Scheme 1-1). Despite its inherent simplicity and significance, however, its synthetic utility was very limited until the mid-1960s. Mainly Grignard reagents and organolithiums were used in earlier examples. In such cases, organic halides are mostly limited to alkyl (C,3) halides. Furthermore, the use of organometals containing Mg and Li is often complicated and limited by their generally low chemoselectivity. Although advances in organocopper chemistry [ l ] over the past three decades have solved many of the difficulties associated with the use of Grignard reagents and organolithiums, a number of other problems have remained unsolved.

R'-M + R2-X R'-R2 + M-X

scheme 1-1

In 1972, Kumada [2] and Corriu [3] independently reported that the reaction of Grignard reagents with alkenyl or aryl halides could be markedly catalyzed by Ni-phosphine complexes, e.g., Cl,Ni(PPh,),. Although many other transition-metal-catalyzed reactions of Grignard reagents with organic halides without the use of phosphines were known, the so- called Kharasch-type reactions [4], with the exception of the Cu-catalyzed procedures [5,6], were not well suited for cross-coupling due to various complications, including extensive cross-homo scrambling.

The discovery of Pd-catalyzed cross-coupling was somewhat more subtle and evolutionary. During the 1975-1976 period, several groups of workers including the present authors' group published various results involving Pd-phosphine complexes. Thus, Cassar "71 reported the Pd-catalyzed cross-coupling reaction of aryl bromides and iodides with sodium acetylides generated in situ by mixing terminal alkynes with NaOMe in DMF (Scheme 1-2). The corresponding reaction using a Ni-phosphine complex did not proceed Catalytically. Similar reactions of alkynes, where the countercations in active species were most probably ammonium and/or Cu', were also reported by Heck [8] and Sonogashira [9] (Scheme 1-2).

1

2 I Palludium- or Nickel-ctitalyzed Cross-coupling

cat. Pd(PPh3), NaOMe. DMF

PhC=CH + RX - P h C S R RX = Phl(95%), H2C=CHBr (52%), PhCHZCHBr (89%)

(71

Cat. Pd(OAc)z(PPh3)2 Et3N

[81 * R'CSCR~ R'C=CH + R2X

R1 R2X yield (9%) Ph H2C=C(Me) Ph t-Bu

R~C=CH +

R'

PhI PhI H;?C=C(Me)Br p-NOzC6H4Br

73 71 88 88

cat. Pd(PPh3),I

P I

cat. CUI, Et2NH * R ~ C = C R ~ R2X

R2X vield (%) - , I Ph PhI 90 HOCH2 PhI 80 Ph H;?C=CHBr 91 HOCH;? H;?C=CHBr 40

Scheme 1-2

Murahashi [ l O , l I] reported the Pd-catalyzed version of the Kumada-Corriu reaction of Grignard reagents, and demonstrated highly stereospecific transformations of (E)- and (a- bromostyrenes into methyl-, vinyl-, and aryl-substituted derivatives (Scheme 1-3). Similar Pd-catalyzed reactions of methyl-, aryl-, and benzylmagnesium bromides were also reported by Fauvarque [I21 and Ishikawa [13]. In these three studies Grignard reagents were the only organometals used catalytically, and organolithiums appeared to be unsatisfactory in the catalytic sense [ 10,111.

cat. Pd(PPhj), PhCH=CHBr + RMgX * PhCH=CHR

RMgX = MeMgl (loo%), H2CzCHMgBr (81%), p-MePhMgBr (86%)

Scheme 1-3

The authors' group reported that alkenylalanes generated in situ by hydroalumination of alkynes could be employed in the Ni-catalyzed alkenyl-aryl coupling [ 141, demonstrating, for the first time, (i) a hydrometallation cross-coupling tandem process and (ii) the use of countercations other than highly electropositive alkaline metals or Mg in the cross-coupling- catalyzed by Ni-phosphine complexes (Scheme 1-4). The Ni-catalyzed alkenylalane cross- coupling was shown to be applicable to the synthesis of conjugated dienes as well [ IS]

1.1 Introduction 3

(scheme 1-5). In this study, however, it was discovered that Pd-phosphine catalysts were more hifly stereospecific and hence distinctly superior to the corresponding Ni-phosphine catalysts. "Ibis m t i o n provided some prototypical examples of efficient, general, and highly stereospecific synthesis of various types of conjugated dienes. In the studies mentioned above, &nylboranes and alkenylborates were used initially, but the results were unsatisfactory, even though later studies by the authors' group showed that alkenylborates were, in fact, satisfactory in some cases [16]. However, the widespread use of alkenylboron derivatives in the Pd- catalyzed cross-coupling is based on the later development of the Suzuki protocol [ 17,181.

ArX cat. Ni(PPh3)4 - HH R HAl(Bu-i)p PhC=CH

H AI(Bu-i)2 H Ar

R ArX yield (%) n-Bu PhBr 85 n-Bu 1-NaphBr 93 Cyclohexyl p-MeC&Br 75

Scheme 1-4

I

H C4H9-n n-CSH1l H HH

'=(:eH9-n M = Ni M = Pd

70%, 95% E, E 74%, 99% E, E

1Hc4H9-n \ H H 5% ML, n-c5H% C4H9-n

H

M = Ni 55%, 90% E, Z M=Pd 55%, 99%E,Z

H H

Seheme 1-5

Collectively, the above-mentioned studies reported during 1975 and 1976 not only established the feasibility of the Pd-catalyzed cross-coupling but also suggested the potential superiority of Pd catalysts over Ni catalysts in many instances. In this chapter, Some noteworthy aspects of the Pd- or Ni-catalyzed cross-coupling reactions of organometals containing Zn, Mg, Al, and Zr will be discussed with emphasis on the Pd- catalyzed cross-coupling reactions of organozincs, sometimes referred to as the Negishi mss-coupling. In so doing, the authors will have to severely and unduly curtail discussion Of the Ni-catalyzed cross-coupling, especially the pioneering and systematic investigation,

4 I Palladium- or Nickel-catalyzed Cross-coupling

mainly in the 197Os, by Kumada, Tamao, and their co-workers [ 19,201 as well as studies ot the Pd-catalyzed cross-coupling reactions of Grignard reagents, most notably a systematic investigation by Linstrumelle since 1978 121-251. It should be noted that the carly investigations mentioned above have paved the way to later developments of the Pd- catalyzed cross-coupling reactions of other organometals containing B [17,18], Sn 126-3 1 I . Cu [32,33], and even Si [34-371, as discussed in other chapters in this book.

1.2 Systematic Survey of Palladium- or Nickel-catalyzed Cross- coupling

1.2.1 Scope with Respect to Metal Counterions and Inhibition of Catalysis by Organolithiums

In several papers [2,7,8,10,14,15] published by 1976 the following generic three-step mechanism for the Pd- or Ni-catalyzed cross-coupling was suggested, although few supporting mechanistic and structural data were provided (Scheme 1-61,

MIL,-- R ~ R ~ M ~ L , ,

R ~ R *

MIL, = Pd or Ni complex

Scheme 1-6

According to this mechanism, the only role of organometallic reagents is to transfer an organic group onto organopalladium or organonickel intermediates. Once diorganylpalladium or diorganylnickel intermediates are formed, their reductive elimination to produce the desired cross-coupling products with the regeneration of active Pd or Ni complexes as well as their subsequent oxidative addition with organic halides should proceed essentially independently of the organometals used. This, in turn, suggested that the Pd- or Ni-catalyzed cross-coupling should be quite general with respect to metal counterions. Indeed, the above discussed shift from Mg to A1 was made with this simplistic notion in mind. With encouragement from the findings shown in Schemes 1-4 and 1-5, a systematic screening of metal counterions was then undertaken. To this end, the cross-coupling reaction between alkynylmetals and aryl halides was chosen, as these classes of compounds were widely and readily available. Some of the favourable results are summarized in Table 1-1 [38].

The results indicate the following.

1. 1-Heptynylmetals containing Zn, B, and Sn led to the desired products in excellent yields. Under the conditions used, their relative reactivity order was Zn>Sn>B.

1.2 Systemtic Survey 5

Table 1-1 Pd-catalyzed reaction of 1 -heptynylrnetals with o-tolyl iodides

n-PentCSCM + 0-To14 THF ' n-PcntC=CTol-o 5% Pd(PPh,),#

7

M Time (h)(') Product yield (%)

Li 24 3

MgBr 24 49

B(n-Buh 3 10

+(i-Buh 3 49

Na 24(b' 58

zacl 1 91

B(n-Bu), 1(b) 92

Al(i-Bu),(n-Bu) 1 38 Sn(n-Bu), 6 83

Starting material (%)

80 41 33

8 76 5

46 10 6

-

@The reaction was run at 20-22 "C unless otherwise stated. lb) Rcflux.

2 1-Heptynyllithium was unsatisfactory, while 1 -heptynylmetaIs containing Na, Mg, and Al led to moderate yields of the desired products. However, more recent results [39] indicate that those containing Mg can be satisfactorily employed.

Although not listed in Table 1-1, 1-heptynylmetals containing HgCl and SiMe, did not produce the desired products in detectable yields. The latter appeared to be totally unreactive under the reaction conditions.

3.

The results obtained with 1-heptynylmetals containing Zn, B, and Sn provided some prototypical examples of the Pd-catalyzed cross-coupling involving these metals. To our knowledge, the reaction of 1-heptynylborate represents the first example of the Pd- catalyzed cross-coupling reaction of organoboron compounds. It is interesting to note that Zn, B, and Sn are currently the three most widely used and satisfactory metals. It should also be emphasized that organometals containing Zn, B, and Sn are by themselves relatively unreactive towards common electrophiles, making their Pd-catalyzed cross-coupling chemoselective in the usual sense. For further discussions of the Pd-catalyzed cross- coupling of organometals containing B [17,18] and Sn [26-311, readers are referred to the corresponding chapters in this book and reviews cited above. In addition to the three metals mentioned above, Mg, Al, Zr (vide infra), and Cu have also been successfully employed in Pd-catalyzed cross-coupling. Thus, synthetic chemists have at their disposal at least seven metals to be considered for this purpose, and selection of the most appropriate metal for a given synthetic task has become very important. For the application of organocoppers, readers are referred to Chapter 5 in this book. In view of the low ionic nature of the C-Si bond, it is not surprising that 1 -heptynyl(trimethyl)silane was unreactive. However, later studies by other workers, notably Kikukawa [34-361 and Hiyama [37], have shown that even organosilanes can be successfully used in Pd-catalyzed cross-coupling. In cases where Some unique advantages associated with the organosilane-based procedures can be found, they may prove useful. For this subject, Chapter 10 in this book should be consulted.

6 1 Palladium- or Nickel-catalyzed Cross-coupling

Although their causes are unclear, the difficulties associated with Hg compounds may be attributable to undesirable redox reactions with Pd. Initially more puzzling was the inability of 1 -heptynyllithium to participate in Pd-catalyzed cross-coupling. Similar difficulties were encountered in an earlier study by Murahashi [lO,ll], and it appears that organolithiums as a class, are generally unsatisfactory, although some exceptions are known [ 1 13. The reasons for the difficulties associated with organolithiums are still not very clear. In a limited number of cases, however, they have been attributed to the excessively high reactivity of organolithiums leading to inhibition of Pd catalysts. Specifically, the stoichiometric reaction of Cl,Pd(PPh,), with two equivalents of LiC=CR, where R = t-Bu, proceeds at least as fast as the corresponding reaction of BrZnCECR to give RC=CC=CR in >95% yield. Yet, the use of eight equivalents of LiCZCR to simulate catalytic conditions leads to the formation of a Pd complex best represented by Li,[Pd(C=CR),] in >95% yield with concomitant release of PPh, but without the production of RC=CC=CR in more than a trace amount [40] (Schemel-7).

2 L i C e R R m - C = R + (LiCI),Pd(PPh3)2

/=* >95% C12Pd(PPh3)2

Y=CR Liz RCS-Pd-CSR + 2 PPh3 + L i C s R

\ 8Li-R R = t-Bu 1 & C R 1

>95%

Scheme 1-7

1.2.2 Cross-coupling between Two Unsaturated Carbon Groups

1.2.2.1 Palladium-catalyzed cross-coupling involving alkynylmetals and related alkynyl nucleophiles: alkynyl-aryl, alkynyl-alkenyl, and alkynyl-alkynyl coupling

Several studies discussed earlier [7-9,381 as well as others published in the 1970s [42,43] have firmly established that the Pd-catalyzed alkynyl-aryl and alkynyl-alkenyl coupling reactions involving several counterions, especially Cu' 191 and Zn2+ [38,41,42], are the methods of choice for the synthesis of arylated alkynes and conjugated enynes [43]. For convenience, the first of the two hyphenated organic groups to form the adjective refers to the organometal or nucleophile, while the second one corresponds to the electrophile. The Sonogashira protocol [9] involving both Cu and Pd catalysts offers a highly convenient procedure. On the other hand, the use of alkynylzincs provides a direct route to terminal alkynes that has not been readily achieved by other methods (Scheme 1-8). It has been repeatedly observed that the corresponding reactions using similarly structured Ni complexes, e.g., [NiCl,(PPh,),], are complicated by side reactions, such as alkyne oligomerization, and that they tend not to permit clean and high-yielding synthesis of the desired alkynes.

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