CATALYTICASYMMETRICSYNTHESIS

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CATALYTICASYMMETRICSYNTHESIS

Second Edition

Edited byIWAO OJIMA

)WILEY-VCHA John Wiley & Sons, Inc., Publication

New York • Chichester • Weinheim • Brisbane • Singapore • Toronto

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Copyright © 2000 by Wiley-VCH, Inc. All rights reserved.

Published simultaneously in Canada.

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For ordering and customer service, call 1-800-CALL-WILEY.

Library of Congress Cataloging-in-Publication Data:Ojima, Iwao, 1945-

Catalytic asymmetric synthesis / edited by Iwao Ojima.—2nd ed.p. cm.

Includes index.ISBN 0-471-29805-0 (alk. paper)1. Asymmetric synthesis. 2. Catalysis. I. Title.

QD262.O35 2000541.3'9—dc21 99-053574

Printed in the United States of America.

1 0 9 8 7 6 5 4 3 2 1

CONTENTS

Preface ix

Preface to the First Edition xi

Contributors xiii

1 Asymmetric Hydrogenation 1

Takeshi Ohkuma, Masato Kitamura, and Ryoji Noyori

2 Asymmetric Hydrosilylation and Related Reactions 111

Hisao Nishiyama and Kenji Itoh

3 Asymmetric Isomerization of Allylamines 145

Susurnu Akutagawa and Kazuhide Tani

Chapter 3 Addendum—1999 162

Xin Wen And Iwao Ojima

4 Asymmetric Carbometallations 165

Ei-ichi Negishi

5 Asymmetric Addition and Insertion Reactions of Catalytically-Generated Metal Carbenes 191

Michael P. Doyle

vi CONTENTS

6 Asymmetric Oxidations and Related Reactions 229

6A Catalytic Asymmetric Epoxidation of Allylic Alcohols 231

Roy A. Johnson and K. Barry Sharpless

Chapter 6A Addendum—1999 281

Xin Wen and Iwao Ojima

6B Asymmetric Epoxidation of Unfunctionalized Olefins andRelated Reactions 287

Tsutomu Katsuki

6C Asymmetric Oxidation of Sulfides 327

Henri B. Kagan

6D Catalytic Asymmetric Dihydroxylation—Discovery andDevelopment 357

Roy A. Johnson and K. Barry Sharpless

6E Recent Advances in Asymmetric Dihydroxylation andAminohydroxylation 399

Carsten Bolm, Jens P. Hildebrand, and Kilian Muftiz

1 Asymmetric Carbonylations 429

Kyoko Nozaki and Iwao Ojima

8 Asymmetric Carbon-Carbon Bond-Forming Reactions 465

8A Asymmetric Cycloaddition Reactions 467

Keiji Maruoka

8B1 Asymmetric Aldol Reactions—Discovery and Development 493

Masaya Sawamura and Yoshihiko Ito

8B2 Recent Advances in Asymmetric Aldol Addition Reactions 513

ErickM. Carreira

8C Asymmetric Ene Reactions 543

Koichi Mikami and Takeshi Nakai

CONTENTS vii

8D Asymmetric Michael Reactions 569

Motomu Kanai and Masakatsu Shibasaki

8E Asymmetric Allylic Alkylation Reactions 593

Barry M. Trost and Chulbom Lee

8F Asymmetric Cross-Coupling Reactions 651

Masamichi Ogasawara and Tamio Hayashi

8G Asymmetric Intramolecular Heck Reactions 675

Yariv Donde and Larry E. Overman

9 Asymmetric Amplification and Autocatalysis 699

Kenso Soai and Takanori Shibata

10 Asymmetric Phase-Transfer Reactions 727

Martin J. O'Donnell

11 Asymmetric Polymerization 757

Yoshio Okamoto and Tamaki Nakano

Epilogue 797

Appendix—List of Chiral Ligands 801

Index 857

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PREFACE

The first edition of Catalytic Asymmetric Synthesis, published in the fall of 1993, was verywarmly received by research communities in academia and industries from graduate students,research associates, faculty, staff, senior researchers, and others. The book was published at thevery moment that the Food & Drug Administration (FDA) in the United States clarified thesituation in "Chiral Drugs," the word "chirotechnology" was created, and chirotechnologyindustries were spawning in the United States and Britain.

As accurately predicted in the preface of the first edition, extensive research on new andeffective catalytic asymmetric reactions have been continuing, in an explosive pace, and it isnow obvious that these catalytic asymmetric processes promoted by man-made chiral catalystswill be the mainstream chemical technology in the 21st century. About five years from thepublication of the original book, there was a clear demand in the synthetic community for anupdated version of this book because advances in the field were accelerated during this period.Accordingly, I have agreed with the publisher to edit a second edition of this book.

In the second edition, I intended to incorporate all important reaction types that I am awareof, while keeping the monumental discovery and initial development of certain processes fromthe first edition, and highlighting recent advances in this field. The original book had 13 chapters(9 general-reaction types), which covered most of the important developments at that time.However, the second edition has 21 chapters (11 general-reaction types) (a total of 21 chaptersfor the 21st century is intriguing, isn't it?), reflecting the tremendous expansion in the scope ofcatalytic asymmetric synthesis in the past several years. In addition to the nine general-reactiontypes covered in the original book, the second edition includes "Asymmetric Carbometallations"(Chapter 4), "Asymmetric Amplification and Autocatalysis" (Chapter 9), and "AsymmetricPolymerization" (Chapter 11). "Cyclopropanation" in the original book has been replaced with"Asymmetric Carbene Reactions" (Chapter 5), which now includes powerful asymmetricintramolecular carbene insertion to C-H bonds. As the Table of Contents shows, there has beensignificant expansion and development in the asymmetric carbon-carbon bond-forming reac-tions (Chapter 8). Thus, this section consists of eight chapters dealing with cycloadditionreactions, aldol reactions, ene reactions, Michael reactions, allylic substitution reactions,

x PREFACE

cross-coupling reactions, and intramolecular Heck reactions. These processes provide veryuseful methods for the highly efficient synthesis of enantio-enriched or enantiopure compoundsof biological, medicinal, agrochemical, and material science related interests.

Once again, the authors of these chapters are all world-leaders in this field, who outline anddiscuss the essence of each catalytic asymmetric reaction. Because the separate list of the chiralligands in the original book was very well received, a convenient list of the chiral ligands withcitation of relevant references appears in this book as an Appendix.

This book will, once again, serve as an excellent reference book for graduate students aswell as chemists at all levels in both academic and industrial laboratories.

Iwao Ojima

PREFACE TO THE FIRST EDITION

Biological systems, in most cases, recognize a pair of enantiomers as different substances, andthe two enantiomers will elicit different responses. Thus, one enantiomer may act as a veryeffective therapeutic drug whereas the other enantiomer is highly toxic. The sad example ofthalidomide is well-known. It is the responsibility of synthetic chemists to provide highlyefficient and reliable methods for the synthesis of desired compounds in an enantiomericallypure state, that is, with 100% enantiomeric excess (% ee), so that we shall not repeat thethalidomide tragedy. It has been shown for many pharmaceuticals that only one enantiomercontains all of the desired activity, and the other is either totally inactive or toxic. Recentmovements of the Food & Drug Administration (FDA) in the United States clearly reflect thecurrent situation in "Chiral Drugs", that is pharmaceutical industries will have to providerigorous justification to obtain the FDA's approval of racemates. Several methods are used toobtain enantiomerically pure materials, which include classical optical resolution via dias-tereomers, chromatographic separation of enantiomers, enzymic resolution, chemical kineticresolution, and asymmetric synthesis.

The importance and practicality of asymmetric synthesis as a tool to obtain enantiomericallypure or enriched compounds has been fully acknowledged to date by chemists in syntheticorganic chemistry, medicinal chemistry, agricultural chemistry, natural products chemistry,pharmaceutical industries, and agricultural industries. This prominence is due to the explosivedevelopment of newer and more efficient methods during the last decade.

This book describes recent advances in catalytic asymmetric synthesis with brief summariesof the previous achievements as well as general discussions of the reactions. A previous bookreviewing this topic, Asymmetric Synthesis, Vol. 5—Chiral Catalysis, edited by J. D. Morrison,Academic Press, Inc. (1985), compiles important contributions through 1982. Another book,Asymmetric Catalysis, edited by B. Bosnich, Martinus Nijhott (1986) also concisely coverscontributions up to early 1984. In 1971, an excellent book, Asymmetric Organic Reactions, byJ. D. Morrison and H. S. Mosher reviewed all earlier important work on the subject and compilednearly 850 relevant publications through 1968, including some papers published in 1969. In theearly 1980s, a survey of publications dealing with asymmetric synthesis (in a broad sense)

xii PREFACE TO THE FIRST EDITION

indicated that the total number of papers in this area of research published in the 10 years afterthe Morrison/Mosher book, that is, 1971-1980, was almost the same as that of all the paperspublished before 1971. This doubling of output clearly indicates the attention paid to thisimportant topic in 1970s. Since the 1980s, research on asymmetric synthesis has become evenmore important and popular when enantiomerically pure compounds are required for the totalsynthesis of natural products, Pharmaceuticals, and agricultural agents. It would not be anexaggeration to say that the number of publications on asymmetric synthesis has been increasingexponentially every year.

Among the types of asymmetric reactions, the most desirable and the most challenging iscatalytic asymmetric synthesis because one chiral catalyst molecule can create millions of chiralproduct molecules, just as enzymes do in biological systems. Among the significant achieve-ments in basic research: (i) asymmetric hydrogenation of dehydroamino acids, a ground-break-ing work by W.S. Knowles et al.; (ii) the Sharpless epoxidation by K. B. Sharpless et al.; and(iii) the second-generation asymmetric hydrogenation processes developed by R. Noyori et al.deserve particular attention because of the tremendous impact that these processes have madein synthetic organic chemistry. Catalytic asymmetric synthesis often has significant economicadvantages over stoichiometric asymmetric synthesis for industrial-scale production of enan-tiomerically pure compounds. In fact, a number of catalytic asymmetric reactions, including the"Takasago Process" (asymmetric isomerization), the "Sumitomo Process" (asymmetric cyclo-propanation), and the "Arco Process" (asymmetric Sharpless epoxidation) have been commer-cialized in the 1980s. These processes supplement the epoch-making "Monsanto Process"(asymmetric hydrogenation), established in the early 1970s. This book uncovers other catalyticasymmetric reactions that have high potential as commercial processes. Extensive research onnew and effective catalytic asymmetric reactions will surely continue beyond the year 2000, andcatalytic asymmetric processes promoted by man-made chiral catalysts will become mainstreamchemical technology in the 21st century.

This book covers the following catalytic asymmetric reactions: asymmetric hydrogenation(Chapter 1); isomerization (Chapter 2); cyclopropanation (Chapter 3); oxidations (epoxidationof allylic alcohols as well as unfunctionalized olefins, oxidation of sulfides, and dihydroxylationof olefms) (Chapter 4); hydrocarbonylations (Chapter 5); hydrosilylation (Chapter 6); carbon-carbon bond-forming reactions (allylic alkylation, Grignard cross-coupling, and aldol reaction)(Chapter 7); phase-transfer reactions (Chapter 8); and Lewis acid-catalyzed reactions (Chapter9). The authors of the chapters are all world-leaders in this field, who outline and discuss theessence of each catalytic asymmetric reaction. (In addition, a convenient list of the chiral ligandsappearing in this book, with citation of relevant references, is provided as an Appendix.)

This book serves as an excellent reference for graduate students as well as chemists at alllevels in both academic and industrial laboratories.

Iwao OjimaMarch 1993

CONTRIBUTORS

Carsten Bolm, Institut fur Organische Chemie, der RWTH Aachen, Professor-Pirlet-Str. 1,D-52056 Aachen, Germany

Erick M. Carreira, Laboratorium fur Organische Chemie, Universitatstrasse 16, ETH-Z,CH-8092 Zurich, Switzerland

Yariv Donde, Department of Chemistry, University of California, Irvine, Irvine, CA 92717-2025

Michael P. Doyle, Vice President, Research Corporation, 101 North Wilmot Road, Suite 250,Tuscon, Arizona 85711

Tamio Hayashi, Department of Chemistry, Graduate School of Science, Kyoto University,Kyoto 606-01, JAPAN

Kenji Itoh, Department of Applied Chemistry, Graduate School of Engineering, NagoyaUniversity, Chikusa, Nagoya 464-01, JAPAN

Henri B. Kagan, Laboratoire de Synthese Asymetrique, Institut de Chimie Moleculaire d'Or-say, Batiment 420, Universite Paris-Sud, Centre d'Orsay, 91405 Orsay Cedex, FRANCE

Motomu Kanai, Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Kongo,Bunkyo-ku, Tokyo 113, JAPAN

Tsutomu Katsuki, Department of Chemistry, Faculty of Science, Kyushu University, 6-10-1Hakozaki, Higashi-ku, Fukouka 812-81, JAPAN

Masato Kitamura, Department of Chemistry, Faculty of Science, Nagoya University,Chikusa, Nagoya 464-01, JAPAN

Chulbom Lee, Department of Chemistry, Stanford University, Stanford, CA 94305

Keiji Maruoka, Department of Chemistry, Graduate School of Science, Hokkaido University,Sapporo 060, JAPAN

xiv CONTRIBUTORS

Koichi Mikami, Department of Chemical Technology, Tokyo Institute of Technology, 2-12-1Ookayama, Meguro-ku, Tokyo 152, JAPAN

Tamaki Nakano, Department of Applied Chemistry, Graduate School of Engineering, NagoyaUniversity, Chikusa, Nagoya 464-01, JAPAN

Ei-ichi Negishi, Department of Chemistry, Purdue University, 1393 Brown Laboratories, WestLafayette, IN 47907-1393

Hisao Nishiyama, School of Material Science, Toyohashi University of Technology, Tem-paku-cho, Toyohashi 441, JAPAN

Ryoji Noyori, Department of Chemistry, Faculty of Science, Nagoya University, Chikusa,Nagoya 464-01, JAPAN

Kyoko Nozaki, Department of Material Chemistry, School of Industrial Chemistry, KyotoUniversity, Yoshida Hon-machi, Sakyo-ku, Kyoto 606-01, JAPAN

Martin J. O'Donnell, Department of Chemistry, Indiana University-Purdue University, 1125East 38th Street, P.O. Box 647, Indianapolis, IN 46223

Masamichi Ogasawara, Department of Chemistry, Graduate School of Science, Kyoto Uni-versity, Kyoto 606-01, JAPAN

Takesi Ohkuma, Department of Chemistry, Faculty of Science, Nagoya University, Chikusa,Nagoya 464-01, JAPAN

Iwao Ojima, Department of Chemistry, State University of New York at Stony Brook, StonyBrook, NY 11794-3400

Yoshio Okamoto, Department of Applied Chemistry, Graduate School of Engineering,Nagoya University, Chikusa, Nagoya 464-01, JAPAN

Larry E. Overman, Department of Chemistry, University of California, Irvine, Irvine, CA92717-2025

Masakatsu Shibasaki, Faculty of Pharmaceutical Sciences, 7-3-1 Kongo, Bunkyo-ku, Tokyo113, JAPAN

Takanori Shibata, Department of Applied Chemistry, Faculty of Science, Science Universityof Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162, JAPAN

Kenso Soai, Department of Applied Chemistry, Faculty of Science, Science University ofTokyo, Kagurazaka, Shinjuku-ku, Tokyo 162, JAPAN

Barry M. Trost, Department of Chemistry, Stanford University, Stanford, CA 94305

1ASYMMETRIC HYDROGENATION

TAKESHI OHKUMA, MASATO KITAMURA, AND RYOJI NOYORIDepartment of Chemistry and Research Center for Materials Science, Nagoya University,Chikusa, Nagoya, Japan 464-8602

1.1. INTRODUCTION

Chiral building blocks are indispensable for the syntheses of biologically active compoundssuch as pharmaceuticals, agrochemicals, flavors, and fragrances as well as in the creation ofadvanced materials. Asymmetric saturation of alkenes, ketones, and imines by hydrogen ororganic hydrogen donors provides an ideal access to chiral alkanes, alcohols, and amines,respectively [1,2]. A small amount of a chiral catalyst repeatedly delivers hydrogen atoms toone of the enantiofaces of substrates, producing large amounts of optically active saturatedcompounds. The chirality multiplication is achieved largely in a homogeneous phase with chiralmolecular catalysts consisting of a metallic element and an optically active organic com-pound^). The molecular structures are highly diverse and, by choosing the handedness ofcatalyst, both enantiomers are available with equal ease. Furthermore, hydrogenation is eco-nomical and environment-conscious, producing no hazardous byproducts. Thus asymmetrichydrogenation has been increasingly important in practical organic syntheses ranging fromresearch to production.

A high reaction rate and enantioselectivity are attainable by appropriate molecular architec-ture of the catalysts and suitable selection of reaction conditions. Historically, highly enantiose-lective hydrogenation was achieved mostly with substrates that have a functionality close to theunsaturated moiety and by use of Rh(I) or Ru(II) complexes that have a chiral diphosphineligand [3]. Recently, various phosphine- and/or nitrogen-based ligands [3,4] have been devel-oped for asymmetric hydrogenation or transfer hydrogenation of simple, unfunctionalizedketones and imines. Some simple olefins can be enantioselectively hydrogenated by earlytransition-metal complexes with a chiral cyclopentadienyl ligand or an Ir catalyst with a chiralamino phosphine ligand. This chapter presents recent advances in this important field. Someasymmetric heterogeneous catalyses are also discussed.

Catalytic Asymmetric Synthesis, Second Edition, Edited by Iwao OjimaISBN 0-471-29805-0 Copyright © 2000 Wiley-VCH, Inc.

2 ASYMMETRIC HYDROGENATION

P(C6H5)2 ,r H , p x(C6H5)2P >-H

H "

CH3CX

(S,S)-BDPP(SKEWPHOS)

(S)-BINAP (S)-BIPHEMP

BINAP: R = C6H5 BIPHEMP: R1 = C6H5; R2 = CH3

TolBINAP: R = 4-CH3C6H4 MeO-BIPHEP: R1 = C6H5; R2 = CH3O

XylBINAP: R = 3,5-(CH3)2C6H3 p-Tol-MeO-BIPHEP: R1 = 4-CH3C6H4; R2 = CH3O

DTBBINAP: R = 3,5-(f-C4H9)2C6H3 di-f-Bu-MeO-BIPHEP: R1 = 3,5-(f-C4H9)2C6H3; R2 = CH3O

(absolute configuration unknown) Fr-MeO-BIPHEP: R1 = 2-furyl; R2 = CH3O

^>MeO-BINAP: R = 4-CH3OC6H4 B|CpEp. R1 = cyc/£>c5H9; tf = CH3

BINAP-S03Na: R = 4-NaOSO2C6H4 B|CHEp. R1 =

Cy-BINAP: R = cyclo-C6H^

(fl,fl)-BisP* V-k^ tetraMe-BITIANPR = 1-adamantyl I (absolute configuration unknown)

(S)-bis-steroidalphosphine

(C6H5)2P(S,S)-CHIRAPHOS

(fl,fl)-CDP

APr-BPE: R = (CH3)2CH

Figure 1.1. C2-chiral diphosphine ligands (in alphabetical order for named compounds).

1.1. INTRODUCTION 3

OR

,,R

(S,S)-DIOP ^^ OCH3 . P~^

D,OP:R<=C6H5;R' = CH3 ft "fS DuPHOS

DIOP-OH: R' = C6H5; R2 = HOCH2 W \^ Me-DuPHOS: R = CH3

MOD-DIOP: R1 = 3,5-(CH3)2-4-(CH3O)C6H2; R2 = CH3 (S,S)-DIPAMP Et-DuPHOS' R = C2H5

CyDlOP: R1 = cyc/o-C6Hli; R2 = CH3 ,P,DuPHOS: R = (CH3)2CH

CH(C2H5)2

(S,S)-FerroPHOS ^-^^ (S,S)-NORPHOS(S)-H -BINAP (fl,S,fl,S)-Me-PennPhos

OR

P(CeH5)2 /^o'PC^eHsJa ^\%v>P(C6H5)2 ^ X

R-N

(S,S)-PYRPHOS (S,S)-RENORPHOS(DEGUPHOS) (S,S,S,S)-RoPHOS

(SH2.2]PHANEPHOS R = CH2C6H5 or f-C4H9

PR2 f\ /

(fl,fl)-TBPC(R,H)-(S,S)-TRAP

EtTRAP: R = C2H5

/-BuTRAP: R = (CH3)2CHCH2 " ' ' (S,S)-2

Figure 1.1. (Continued)

4 ASYMMETRIC HYDROGENATION

R2R CH3O

XQjHsfe

(fl)-(S)-BPPFA (2S,4S)-BPPM (S)-CAMP

BPPFA: X = (CH3)2N ODD». A,r = R =

3: x = _^N(CH2)2(CH3)N R'-CAPP: Ar = R = C6H5; X = R'NHCO

BPPFOH: X = HO BCPM: Ar = C6H5; R = cyc/o-CgH, , ; X = (CH3)3COCO

MCCPM: Ar = C6H5; R = cyclo-C6^ , ; X = CH3NHCO

m-CHgPOPPM: Ar = R = 3-CH3C6H4; X = (C6H5)2PO

MCCXM: Ar = 3,5-(CH3)2C6H3; R = cyclo-CeHn;X = CH3NHCO

MOD-BCPM: Ar = 3,5-(CH3)2-4-(CH3O)C6H2;R = cycto-CeHu; X = (CH3)3COCO

P(cyc/oC6H11)2 X^NvJP(CeH5)2 >,,

Ar °6 5 (/7)-(S)-JOSIPHOS

(S,fl,fl,fl)-TMO-DEGUPHOS JOSIPHOS R =cyc/oC6H1i; Ar = QH5(fl)-cy2-BIPHEMP

Ar = 2,4,6-(CH3O)3C6H2; XYLIPHOS: R = 3,5-(CH3)2C6H3; Ar = C6H5

X = (CH3)3COCO xyl2PF-Pxy!2: R = 3,5-(CH3)2C6H3; Ar = 3,5-(CH3)2C6H3

MOD-XYLIPHOS: R = 3,5-(CH3)2-4-((CH3)2CH)2NC6H2;

^ ^ p(C6H5)(C6H4-3-S03Na)i)2 f V-P(C6H5)2 P^Hsk (

\_ (R)-PROPHOS y-

(diastereo mixture)BENZPHOS: R = C6H5CH2

. „Nf-- V'

^ — ' (1S,2S,3fl,4S,5S)-5

Figure 1.2. Phosphine ligands without C2 chirality (in alphabetical order for named compounds).

1.1. INTRODUCTION 5

OC6H5

H,°

-^^ rr̂ PO-V,, or^°PAr2

(S,S)-BDPCH (S,S)-BDPCP Ph-B-GLUP(S,fl)-BICPO F

Ph-B-GLUP: Ar = C6H5

7: Ar = 3,5-((CH3)3Si)2C6H3OC6H5

A 0.OP(CeHs)2

6 5 2 "OP(CeH5)2

OH OH Y ""OP(C6H3-3,5-(CH3)2)2

(R,fl,fl)-spirOP V^Ph-B-GLUP-OH

aO^ H

V-Q H

VM3n5;2rw wrVM5n5,2 Q-

H9 (C6H5)2PO OP(C6H5)2

10

Figure 1.3. Bisphosphinite ligands.

NHP(C6H5)2NHP(C6H5)2

(S)-Cp,Cp-lndoNOP(R)-BDPAB (1S,2R)-DPAMPP (fl)-H8-BDPAB

vr-OP(cyc/o-C5H9)2 CH3N O CH3N 9

R12P PR22 (C6H5)2P P(cycto-C5H9)2

(OC)3Cr P(cyc/o-C5H9)2(S)-isoAlaNOP (S)-Ph,Cp-methyllactamide

(S,2S)-Cr(CO)3-Cp,Cp-lndoNOPPh.Cp-isoAlaNOP: R1 = C6H5; R

2 = cyc/o-C5H9

Cp.Cp-isoAlaNOP: R1 = R2 = cyc/o-C5H9

Figure 1.4. Amido- or aminophosphine ligands (in alphabetical order). (Continued on next page.)

6 ASYMMETRIC HYDROGENATION

J~\ 1 °R1

0^NX^OPR12 I,,, 0P(C6H5)2

PR22 INP(C6H5)2

(S)-oxoProNOP R2

Ph.Ph-oxoProNOP: R1 = R2 = C6H5 (R)-PINDOPHOS

Cp.Cp-oxoProNOP: R1 = R2 = cyc/o-C5H9 PINDOPHOS: R1 = 7-indolyl; R2 = (CH3)2CH

Cy,Cy-oxoProNOP: R1 = R2 = cydo-CeH^ 11: R1 = 1-naphthyl; R2 = cycto-C5H9

OP(C6H5)2

NP(C6H5)2/

(S,S)-PNNP (S)-PROLOPHOS

Figure 1.4. (Continued)

CH3O

NH2

(S)-DAIPEN (S,S)-DMDPEN (S,S)-DPEN

CH3O

Figure 1.5. Amine ligands.

1.2. CHIRAL LIGANDS 7

(fl)-AMBOX (fl)-DHPPEI (fl,fl)-PDPBI

(S)-PPEI (S)-15 (S,S)-16

Figure 1.6. Pyridines, phenanthrolines, and oxazole ligands.

1.2. CHIRAL LIGANDS

A suitable combination of a metal species and chiral organic ligand [3,4] is the key factor toprepare high-performance catalysts for asymmetric hydrogenation. The electron-donatingligands often increase the hydride-donating ability of catalytic species. The stereo-regulation isnormally achieved by utilizing repulsive interactions between substituents of the ligands andsubstrates, although bulky groups tend to decrease the reactivity. The stereochemical controlwith an attractive interaction is also important to achieve a high catalytic activity.

Development of optically active phosphine ligands, especially C2-chiral diphosphines, usedlate transition-metal complexes as (pre)catalysts and provided a great advancement in asym-metric hydrogenation. Commonly used phosphorus-based ligands are listed in Figures 1.1-1.4.Chiral nitrogen-based ligands are also important, particularly for asymmetric transfer hydro-genation. The structures are classified in Figures 1.5-1.9. The chiral complexes with cyclopen-tadienyl ligands are given in the main text.

NHSQ,C6H4-4-CH3

NHg

(fl,R)-TsDPEN

Figure 1.7. N-Substituted (di)amines.

8 ASYMMETRIC HYDROGENATION

2"OH

(fl)-20

NH2

(1fl,2S)-21

cinchona alkaloids

cinchonidine: R1 = CH2=CH; R2 = H; Y = H

quinine: R1 = CH2=CH; R2 = H; Y = CH3O

MeOHCd: R1 = C2H5; R2 =CH3; Y = H

NHCH3

OH

(S,S)-22 (S>S).23

Figure 1.8. Amino alcohols.

*'V*k /N,

1 /-N N—r^n . / H H

/ \^ \=/ p"h2 Ph2

(S)-26: R1 = H; R2 = (CH3)3C (S,S)-28 ^^

(S)-27: R1 = CH3; R2 = (CH3)2CH

r^^X^N \=/ <f V.P

O

(S)-30

Figure 1.9. Amino and imino phosphine ligands.

1.3. HYDROGENATION OF OLEFINS 9

1.3. HYDROGENATION OF OLEFINS

In the late 1960s, the discovery of the Wilkinson's hydrogenation catalyst, RhCl[P(C6H5)3]3,stimulated attempts to create tertiary stereogenic carbon atoms by enantioselective hydrogena-tion of olefms by using optically active transition-metal complexes [5]. In the beginning, onlya very low enantioselectivity was obtained in hydrogenation of 2-phenylacrylic acid and2-phenyl-l-propene with certain chiral tertiary phosphine-modified Rh complexes as catalysts[6]. However, the situation was soon dramatically changed by the invention of well-designedRh complexes containing—among others—DIOP [7], CAMP [8], and DIPAMP [9] as ligandsused for asymmetric hydrogenation of a-(acylamino)acrylic acids. This chemistry later becamethe standard method to synthesize optically active amino acids. In the mid-1980s the discoveryof BINAP-Ru complexes significantly expanded the scope of olefinic substrates for asymmetrichydrogenation [lc]. Now a variety of natural and unnatural chiral compounds are accessible ina practical manner. Recently researchers have tried to extend the asymmetric catalysts from thelate transition-metal complexes tothe early transition-metal complexes.

1.3.1. Functionalized Olefins

Considerable success has been realized for asymmetric hydrogenation of functionalizedalkenes. However, there is no universal catalyst that ensures generally high enantioselectivityfor a wide range of substrates. The limitation has been overcome largely by combinatorialinvestigation of transition metals and chiral ligands together with mechanistic understanding ofthe multistep catalytic reaction.

1.3.LI. Enamides Enantioselective hydrogenation of a-hydroxycarbonyl- or oc-alkoxycar-bonyl-substituted enamides is effectively catalyzed by a number of Rh complexes with a chiralligand to produce the corresponding amino acid derivatives with >90% ee [3b,10]. One or twophosphorus atoms are incorporated into the phosphine, phosphinite, and aminophosphineligands, where the chirality is installed at the phosphorus or carbon atoms or in the molecularframework. Chiral ligands may be immobilized onto polymers. In most cases, the efficiency ofcatalysts has been examined with (Z)-2-(acetamido)cinnamic acid, 2-(acetamido)acrylic acid,and their methyl or ethyl esters. The reaction is generally carried out in alcoholic solvents at1-10 atm of hydrogen. The cationic complexes are most commonly used. Selected examplesare compiled in Scheme 1.1.

High catalytic activities have been achieved by the PYRPHOS- [18], PPCP- [20],BICHEP- [21], Et-DuPHOS-Rh [19] complexes among others, allowing the reaction with asubstrate-to-catalyst molar ratios (S/C) as high as 50,000. With a [2.2]PHANEPHOS-Rhcomplex, the reaction proceeds even at -45°C [27]. Supercritical carbon dioxide, a uniquereaction medium, can be used in the DuPHOS and BPE-Rh-catalyzed hydrogenation [43]. Ahighly lipophilic counteranion such as tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF)or trifluoromethanesulfonate is used to enhance the solubility of the cationic Rh complexes.Under the most suitable reaction conditions of 102 atm of carbon dioxide, 1 atm of hydrogen,and 22°C, oc-amino acid derivatives are produced with up to 99.7% ee.

Two-phase catalysis with water and organic solvent is industrially important because of theeasy catalyst/product separation. For achieving sufficient water solubility of catalysts, a highlypolar group such as amino, hydroxy, hydroxycarbonyl, or hydroxysulfonyl function is intro-duced into a chiral organic ligand. a-(Acetamido)cinnamic acid is hydrogenated in up to 94%optical yield by using a Rh complex of CHIRAPHOS bearing sulfonate groups or quarternaryamino moieties in the P-phenyl rings [44]. Reaction of sodium (X-(acylamino)cinnamate in

10 ASYMMETRIC HYDROGENATION

COOR2 chiral Rh catalyst+ H2

y—NHCOCHj NHCOCH,

% ee of Product (confign)

R^C^ R^CgHs R ' = H R1 = H

Ligand R2 = H R2 = CH3 R2 = H R2 = CH3 Ref

diphosphine(7?,7?)-DIOP 85 (R) 13 (R) 1(7?,7?)-DIPAMP 96(5) 94(5) 9(5)-(7?)-BPPFA 93 (S) 11(25,45)-BPPM 91 (7?)a 12(5,5)-CHIRAPHOS 99 (7?) 91 (7?) 13(5,5)-NORPHOSfc 95(5) 90(7?) 14(5)-BINAP 100(7?) 98(7?)a 15(7?)-CYCPHOS 88 (5) 16(S,S)-BDPP 92 (/?) 17(#,fl)-PYRPHOS 99 (5) 18(5,5)-Et-DuPHOS 99(5) 99.4(5) 19(l/?,2/?)-PPCP 96(5) 87(5) 20(/?)-BICHEP 98 (5)c 21(7?,7?)-BICP 99 (5)a 22(7?,/?)-Me-BPE 85 (7?) 23(7?,7?)-(5,5)-/-BuTRAP 92 (5) 24(7?,7?)-(5,5)-EtTRAP 96 (7?) 24(5,5)-1 90 (7?) 93 (7?) 93 (7?) 91 (7?) 25(5,5)-BIPNOR >98 (5) 26(7?)-[2.2]PHANEPHOS 98(7?) 99.6(7?) 27(15,25,37?,45,55)-5 87(7?) 87(7?) 28(5,5)-2 97.1(7?) 97.7(7?) 64.1(7?) 29(5,5)-BisP* 98.6(7?) 99.9(7?) >99.9 (7?) 30(5,5)-FerroPHOS 98.9(7?) 97.6(7?) 98.2(7?) 97.5(7?) 31(5,5,5,5)-RoPHOS 93.5(5) 97.5(5) 32

diphosphinitePh-p-GLUP 91 (5) 337 99.0(5) 97.6(5) 348 97.0(7?) 96.3(7?) 34(7?,7?,7?)-spirOP 97.9(7?) 95.7(7?) >99.9 (7?) 99.0(7?) 3510 84(5) 66(5) 36(7?,5)-BICPO 96.1 (5) 37

(Continued on next page.)

Scheme 1.1.

1.3. HYDROGENATION OF OLEFINS 11

% ee of Product (confign)

R^CfcHj R^CeHg R1 = H R^H

Ligand R2 = H R2 = CH3 R2 = H R2 = CH3 Ref

aminophosphine phosphinite(5)-PROLOPHOS 80 (5) 38(fl)-PINDOPHOS 91(5) 90(5) 39(15,2/?)-DPAMPP 98.3 (R) 40(5)-ll 9l(R)a 94(R)a 41

diaminophosphine(5,5)-PNNP 93.8(5) 89.5(5) 42

a Hydrogenation of the W-benzoyl derivative. b The hydrogenation conditions form RENORPHOS.c Hydrogenation of the ethyl ester derivative.

Scheme 1.1. (Continued)

aqueous solution gives the saturated product in 90% optical yield by using a water-soluble Rhcomplex of a PYRPHOS-type ammonium ligand [45]. A Ph-p-GLUP-OH-Rh complex hydro-genates various (x-(acetamido)cinnamates in water containing sodium dodecylsulfate (SDS) asa surfactant to yield phenylalanine derivatives with 96-98% ee [46]. Without SDS the enan-tioselectivities remain to be ca. 80% ee. In hydrogenation of methyl a-(acetamido)cinnamatewith a DIOP-OH-Rh complex, the optical yield is increased from 1.5% to 76.6% [47]. Thisincrease may be ascribed to the formation of micro-heterogeneous systems of colloidal dimen-sions on micelles. Use of polymeric surfactants generates swelled micelles that enclose catalysts,which can be separated by filtration [48]. These polymeric micelles represent a borderline caseto polymer-attached catalysts.

Many trials on polymer fixation of homogeneous chiral Rh catalysts have been made sincethe pioneering work in 1976 [49]. Chiral diphosphines such as DIOP and BPPM are attachedto a cross-linked polystyrene matrix containing hydrophilic hydroxyethyloxycarbonyl function.The immobilized Rh catalysts swell in an ethanol-benzene-mixed solvent and hydrogenatea-(acetamido)cinnamic acid with up to 90% ee [50]. Rh complexes of PYRPHOS bound to apolyethylene oxide-grafted styrene matrix and to a macroporous silica gel show higher reactivityand selectivity than the homogeneous complexes, giving N-acetylphenylalanine with 97% ee[51] and its methyl ester with 100% ee, respectively [52]. A nitrogen-based chiral ligand derivedfrom natural proline is also anchored on silica and a modified USY zeolite. With these Rhcomplexes, W-benzoyl phenylalanine ethyl ester is obtained with 92-99% ee [53]. Cationic Rhcomplexes can be ionically bound to cation exchangers such as sulfonated styrene-divinylben-zene copolymer and arylsulfonic acid-functionalized silica gel [54]. Such immobilized Ph-p-GLUP-Rh complexes yield phenylalanine derivatives with ca. 95% ee. Water-solubleamine-functionalized BDPP and CHIRAPHOS derivatives are fixed on strongly acidic cation-exchange resin Nafion-H. The Rh complexes give similar enantioselectivities to the correspond-ing homogeneous catalysts [55]. In such ionic binding of the catalysts, however, acatalyst-leaching problem is always present.

In contrast to the high enantioselectivities obtained for the Z substrates, hydrogenation ofthe E isomers usually proceeds very slowly and in a poor optical yield partly due to the EIZdouble-bond isomerization. The enantioselectivity in the BINAP-Rh-catalyzed hydrogenationof E enamides is enhanced in an aprotic solvent THF to minimize the isomerization [15,56].

12 ASYMMETRIC HYDROGENATION

(S)-BINAP-Rh+

+ H2 • • =NHCOR3 v. S* NHCOR3

R 1=ArorH \^ s' R

(fl)-BINAP-Rh+

R1 //" "\ R1

VPOOR^ /^ ^^x. I popin^L/kJUrT \^ -xtAJvJn+ H2 Y

NHCOR3 (S)-BINAP-Rh+ NHCOR3

R1 = Ar S

Scheme 1.2.

Scheme 1.2 illustrates the relationship between the double-bond geometry, the configuration ofthe BINAP ligand, and the stereochemistry of the products.

A DuPHOS-Rh catalyst reduces both E and Z enamides with a high enantioselectivity evenin an alcoholic solvent without E/Z isomerization [57]. Notably, P,|3-disubstituted a-enamidesare also smoothly hydrogenated to ^-branched a-amino acids [58]. Sterically less-hinderedMe-DuPHOS- and Me-BPE-Rh catalysts provide a high enantioselectivity. The cationic Rhcomplexes of TRAP [24], BisP* [30], and [2.2]PHANEPHOS [27] are also active for hydro-

R

R2

l /-UCOOCH3 chiral Rh catalyst

NHCOCHj NHCOCHa

(f?,fl)-Me-BPE-Rh

NHCOCHj NHCOCBj NHCOCBj

98.2% ee 98.3% ee 97% ee

.COOCHg

NHCOCHj

90.6% ee 95.9% ee

(fl,fl)-(S,S)-PrTRAP-Rh

f-C4H9(C6H5)2SiQ ?-C4H9COO NHCbz

.COOCH3

NHCOCH3 NHCOChb

88% ee 97% ee 82% ee

Scheme 1.3.

1.3. HYDROGENATION OF OLEFINS 13

R2

chiral catalyst

NR'COR5 . ._. . NR4COR5

1-100atm

CHs NHCOCB3

91 % ee 86% ee >99% ee

(S,S)-CHIRAPHOS-Rh (fl)-[2.2]PHANEPHOS-Rh (S)-BINAP-Rh

clozylacon precursor metalaxyl precursor

(S)-BINAP-Ru 66% ee (fl,fl)-Me-DuPHOS-Rh 98% ee(100% ee after single crystallization) (S)-cy2-BIPHEMP-Rh 99% ee

(2S,4S)-BPPM-RhH2

CHgOHorHaO1 atm

Scheme 1.4.

96% ee (X = OCH3)98% ee (X = C2H5)

genation of |3,(3-disubstituted ot-enamides. Hydrogenation of a-enamides possessing dissimilar(3-substituents allows the simultaneous generation of an additional p-stereogenic center in theproduct. Both erythro and threo ^-substituted amino acids are produced through hydrogenationof the E and Z enamides using Me-BPE-Rh complex (Scheme 1.3) [58]. Thus p-methyltrypto-phan with 97% ee can be prepared by use of Me-DuPHOS-Rh complex [59]. The cationicEt-DuPHOS- and Me-BPE-Rh complexes do not reduce isolated carbon-carbon double ortriple bonds in the time frame for hydrogenation of the a-enamide moiety, allowing the synthesisof allylglycine derivatives [60]. Both erythro- and ^/zreo-p-hydroxy-oc-amino acids with highenantiopurities are prepared by enantioselective hydrogenation of (Z)-p-siloxy-a-(acetamido)acrylates and (£)-p-pivaloyloxy-a-(acetamido)acrylates by using a TRAP-Rhcomplex [61]. The PrTRAP-Rh catalyst gives higher enantioselectivity than catalysts with Et-and BuTRAP. This method has been applied to the synthesis of 2,3-diarnino carboxylic acidswith 79-82% ee [62]. Use of the more easily removable N-protecting groups such as Cbz

14 ASYMMETRIC HYDROGENATION

and Boc enhances the synthetic utility of asymmetric hydrogenation of enamides.[2.2]PHANEPHOS-, Et-DuPHOS-, and Pr-DuPHOS-Rh catalysts promote highly enantiose-lective hydrogenation of the N-Cbz or -Boc-protected substrates [27,39,63].

The chiral Rh catalytic systems are applicable to the synthesis of a variety of optically activeoc-amino acids, including (S)- and (/?)-aromatic, -heteroaromatic, and -aliphatic alanine deriva-tives [10,34,64]. Functionalized substituents such as methylhydroxyphosphinylmethyl [65] andalkoxycarbonylamino group [27] may be introduced to the (3-position of a-(acylamino)acry-lates. The hydroxy- or alkoxycarbonyl group can be replaced by other electron-withdrawinggroups [10] such as carbamoyl, keto, cyano, dialkoxyphosphoryl [32,66], and alkylhy-droxyphosphinyl groups [67]. N-Aryl-substituted enamides are also usable as substrates,opening an enantioselective route to fungicidal agrochemicals such as clozylacon and metalaxyl[68]. Several examples recently reported are shown in Scheme 1.4.

chiral Rh catalyst+ H2

NHCOCH3 NHCOCH33 1-14atm 3

and its E isomer

NHCOCH, NHCOCHj NHCOCH3

>99% ee 92% ee >99% ee(S,S)-Me-BPE-Rh (S,S)-Me-BPE-Rh (S,S)-Me-DuPHOS-Rh

Substrate Product

R E:Z Ligand % ee Confign

H — (/?,/?)-Me-BPE 95.2 RH — (fl)-BDPAB 92.9 RH — (/?)-H8-BDPAB 96.8 RCH3 0:100 (5,5)-DIOP 92 RCH3 50:50-20:80 (fl^-Me-BPE 95.4 RCH3 65:35 (R,R)-CDP 92 RCH3OCH2O

a (/?,/?)-Me-DuPHOS 97 SCH3OCH2O

a (/?,/?)-BICP 94 Sa Unknown.

Scheme 1.5.

1.3. HYDROGENATION OF OLEFINS 15

,COOR1

(S)-BINAP-Rh =

(S,S)-CHIRAPHOS-Rh S^ NHCOFT

COOR1I1

NHCOR2

: Ar or H(S)-BINAP-Ru(S,S)-CHIRAPHOS-Ru

Scheme 1.6.

Existence of the oc-carboxyl or alkoxycarbonyl function in a-(acylamino)acrylates is not arequisite condition for attaining a high reactivity and enantioselectivity. The chiral diphosphine-and bisaminophosphine-Rh complexes hydrogenate a-aryl-substituted oc-enamides, providingan entry to a-arylamines as well as (3-amino alcohol derivatives with >92% ee (Scheme 1.5)[69-73]. Both E and Z enamides are hydrogenated in a high optical yield with the same senseof enantioselectivity, thus allowing use of the EIZ mixture of (3-substituted oc-arylenamides.l-Acetamido-2,3-benzocyclopentane and -2,3-benzocyclohexane are synthesized with up to>99% ee by Me-BPE-Rh-catalyzed hydrogenation [73]. Me-DuPHOS-Rh complex can beused for the hydrogenation of cc-/-alkyl-substituted cc-enamide [73].

Unlike the Rh-based hydrogenation of a-(acylamino)acrylates, the corresponding Ru chem-istry has not been studied extensively. Ru complexes of (S)-BINAP and (S,S)-CHIRAPHOScatalyze the hydrogenation of (Z)-a-(acylamino)cinnamates to give the protected (S)-pheny-lalanine with 92% ee [74] and 97% ee [75], respectively. It is interesting that the Rh and Rucomplexes with the same chiral diphosphines exhibit an opposite sense of asymmetric induction(Scheme 1.6) [13,15,56,74,75]. This condition is due primarily to the difference in the mecha-nisms; the Rh-catalyzed hydrogenation proceeds via Rh dihydride species [76], whereas theRu-catalyzed reaction takes place via Ru monohydride intermediate [77]. The Rh-catalyzedreaction has been studied in more detail by kinetic measurement [78], isotope tracer experiments[79], NMR studies [80], and MO calculations [81]. The stereochemical outcome is under-standable by considering the thermodynamic stability and reactivity of the catalyst-enamidecomplexes.

l-(Formamido)alkenylphosphonates and 7V-acyl-l-alkylidenetetrahydroisoquinolines arehydrogenated at 1 -4 atm of hydrogen with almost perfect enantioselection by use of BINAP-Rucomplexes [77a,82] (Schemes 1.7 and 1.8). The bulkier size of the sp -hybridized, tetrahedrallyarranged phosphonic ester group in comparison with the sp -hybridized, planar carboxylic esteror the constrained cyclic system results in the high asymmetric induction. The BINAP-Rumethod has provided a straightforward way to highly enantiomerically pure a-amino phos-

(S)-BINAP-RuH2

NHCHO CH3OH NHCHO1 atm

R = H, CH3, C6H5, etc 97-98% ee

Scheme 1.7.