Name Reactions for Functional Group Transformations...The more complex functional groups, formed using additional elements or by concatenation of simpler groups, play a similar unifying

Name Reactions for Functional Group Transformations

Edited by

Jie Jack Li Pfizer Global Research & Development

E. J. Corey Harvard University

B I C L N T E N N I A L

WILEY-INTERSCIENCE A John Wiley & Sons, Inc., Publication

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Edited by

Jie Jack Li Pfizer Global Research & Development

E. J. Corey Harvard University

B I C L N T E N N I A L

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Library of Congress Cataloging-in-Publication Data:

Name reactions for functional group transformations / edited by Jie Jack Li, E. J. Corey.

p. cm. Includes index.

1. Organic compounds-Synthesis. 2. Chemical reactions. I. Li, Jie Jack.

QD262.N36 2007 5 4 7 l . 2 6 ~ 2 2 2007010254

ISBN 978-0-471-74868-7

11. Corey, E. J.

Printed in the United States of America.

1 0 9 8 7 6 5 4 3 2 1

Dedicated To

Li Wen-Liang and Chen Xiao-Ying


vii

Foreword

Part of the charm of synthetic organic chemistry derives from the vastness of the intellectual landscape along several dimensions. First, there is the almost infinite variety and number of possible target structures that lurk in the darkness waiting to be made. Then, there is the vast body of organic reactions that serve to transform one substance into another, now so large in number as to be beyond credibility to a non-chemist. There is the staggering range of reagents, reaction conditions, catalysts, elements, and techniques that must be mobilized in order to tame these reactions for synthetic purposes. Finally, it seems that new information is being added to that landscape at a rate that exceeds the ability of a normal person to keep up with it. In such a troubled setting any author, or group of authors, must be regarded as heroic if through their efforts, the task of the synthetic chemist is eased.

Modern synthetic chemistry is a multifaceted discipline that greatly benefits from the development of unifying concepts. One of the most useful of these is the idea of the “functional group,” generally considered to be a specific collection of connected atoms that occur frequently in organic structures and that exhibit well defined and characteristic chemical behavior. The simplest and most common functional groups (e.g., C=C, CHO, OH, COOH, NH2) dominate the organization of entry-level organic chemistry textbooks and provide a framework for understanding the fundamentals of the subject. The more complex functional groups, formed using additional elements or by concatenation of simpler groups, play a similar unifying role. This volume, Name Reactions for Functional Group Transformations, provides a survey of important transformations that are characteristic of the whole range of functional groups and also serve to interconnect them. In the more than six hundred pages that follow, a highly qualified team of nineteen authors from academia and industry has provided an up-to-date account of forty-seven major classes of functional group transformations. The reviews are clear, concise, and well-referenced. This book serves as a fine companion to the first volume of this series, Name Reactions in Heterocyclic Chemistry.

E. J. Corey

November 13,2006

viii

Preface

This book is the second volume of the series Comprehensive Name Reactions, an ambitious project conceived by Prof. E. J. Corey of Harvard University in the summer of 2002. Volume 1, Name Reactions in Heterocyclic Chemistry, was published in 2005 and was warmly received by the organic chemistry community. After publication of the current Volume 2 in 2007, we plan to roll out Volume 3, Name Reactions on Homologation, in 2009; Volume 4, Name Reactions on Ring Formation in 201 1; and Volume 5, Name Reactions in Heterocyclic Chemistry-2, in 20 13, respectively.

Continuing the traditions of Volume 1, each name reaction in Volume 2 is also reviewed in seven sections: 1 . Description; 2. Historical Perspective; 3. Mechanism; 4. Variations and Improvements; 5. Synthetic Utility; 6 . Experimental; and 7. References. I also have introduced a symbol [R] to highlight review articles, book chapters, and books dedicated to the respective name reactions.

I have incurred many debts of gratitude to Prof. E. J. Corey. What he once told me - “The desire to learn is the greatest [email protected] God” - has been a true inspiration. Furthermore, it has been my great privilege and a pleasure to work with a collection of stellar contributing authors from both academia and industry. Some of them are world-renowned scholars in the field; some of them have worked intimately with the name reactions that they have reviewed; some of them even discovered the name reactions that they authored in this book. As a consequence, this book truly represents the state-of-the-art for Name Reactions for Functional Group Transformations.

I welcome your critique.

Jack Li

October 24,2006

ix

Contributing authors:

Dr. Nadia M. Ahmad Institute of Cancer Research Haddow Laboratories 15 Cotswold Road Sutton, Surrey SM2 5NG, UK

Dr. Marudai Balasubramanian Research Informatics Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48105

Dr. Alice R. E. Brewer Novartis Horsham Research Centre Wimblehurst Road Horsham, West Sussex RH12 5AB, UK

Dr. Julia M. Clay Chemistry Department Princeton University Princeton, NJ, 08544-1009

Dr. Timothy T. Curran Department of Chemical R&D Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48 105

Dr. Matthew J. Fuchter Department of Chemistry Imperial College London Exhibition Road, London SW7 2AZ, UK

Dr. Paul Galatsis Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48105

Prof. Gordon W. Gribble Department of Chemistry 6 128 Burke Laboratory Dartmouth College Hanover, NH 03755

Dr. Timothy J. Hagen Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48 105

Dr. Daniel D. Holsworth Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor. MI 48 105

Dr. Donna M. Iula Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48 105

Dr. Jacob M. Janey Process Research Merck Research Laboratories

Rahway, NJ 07065-0900 P. 0. BOX 2000 RY800-B363

Dr. Manjinder S. La11 Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48 105

Dr. Jie Jack Li Department of Chemistry Pfizer Global Research & Development 2800 Plymouth Road Ann Arbor, MI 48 105

x

Dr. Jin Li Medicinal Chemistry BioDuro No. 5, KaiTuo Road Beijing, PRC 100085

Dr. Dustin J. Mergott Lilly Research Laboratories Eli Lilly and Company Indianapolis, IN 46285

Prof. Richard J. Mullins Department of Chemistry Xavier University 3800 Victory Parkway Cincinnati, OH 45207-4221

Prof. Kevin M. Shea Department of Chemistry Clark Science Center Smith College Northampton, MA 01063

Prof. John P. Wolfe Department of Chemistry University of Michigan 930 N. University Avenue Ann Arbor, MI 48 109

xi

Table of Contents

Foreword Preface Contributing Authors

Chapter 1 Asymmetric Synthesis 1 .I CBS reduction 1.2 Davis chiral oxaziridine reagents 1.3 Midland reduction 1.4 Noyori catalytic asymmetric hydrogenation 1.5 Sharpless asymmetric hydroxylation reactions

Chapter 2 Reduction 2.1 Eschweiler-Clark reductive alkylation of amines 2.2 Gribble reduction of diary1 ketones 2.3 Luche reduction 2.4 Meerwein-Ponndorf-Verley reduction 2.5 Staudinger reaction 2.6 Wharton reaction

Chapter 3 Oxidation 3.1 Baeyer-Villiger oxidation 3.2 Brown hydroboration reaction 3.3 Burgess dehydrating reagent 3.4 Corey-Kim oxidation 3.5 Dess-Martin periodinane oxidation 3.6 Tamao-Kumada-Fleming oxidation 3.7 Martin’s sulfurane dehydrating reagent 3.8 Oppenauer oxidation 3.9 Prilezhaev reaction 3.10 Rubottom oxidation 3.1 1 Swern oxidation 3.12 Wacker-Tsuji oxidation 3.13 Woodward cis-dihydroxylation

vii viii ix

1 2 22 40 46 67

85 86 93 112 123 129 152

159 160 183 189 207 218 237 248 265 274 282 29 1 309 327

xii

Chapter 4 Olefination 4.1 Chugaev elimination 4.2 Cope elimination reaction 4.3 Corey-Winter olefin synthesis 4.4 Perkin reaction (cinnamic acid synthesis) 4.5 Perkow vinyl phosphate synthesis 4.6 Ramberg-Bgcklund olefin synthesis 4.7 Shapiro reaction 4.8 Zaitsev elimination

Chapter 5 Amine Synthesis 5.1 Fukuyama amine synthesis 5.2 Gabriel synthesis 5.3 Leuckart-Wallach reaction

Chapter 6 Carboxylic Acid Derivatives Synthesis 6.1 Fischer-Spier esterification 6.2 Mukaiyama esterification 6.3 Ritter reaction 6.4 Strecker amino acid synthesis 6.5 Yamada coupling reagent 6.6 Yamaguchi esterification

Chapter 7 7.1 Balz-Schiemann reaction 7.2 Buchwald-Hartwig reactions 7.3 Haloform reaction 7.4 Hunsdiecker reaction 7.5 JappKlingemann hydrazone synthesis 7.6 Krapcho decarboxylation 7.7. Nef reaction 7.8 Prins reaction 7.9 Regitz diazo synthesis 7.10 Sommelet reaction

Miscellaneous Functional Group Manipulations

333 334 343 354 363 369 386 405 414

423 424 43 8 45 1

457 458 462 47 1 477 5 00 545

551 552 5 64 610 623 630 63 5 645 653 658 689

xiii

Appendixes Appendix 1. Table of Contents for Volume 1 :

Appendix 2. Table of Contents for Volume 3: Name Reactions in Heterocyclic Chemistry

Name Reactions for Chain Extension

Appendix 3. Table of Contents for Volume 4: Name Reactions f o r Ring Formation

697

697

700

703

Appendix.4 Table of Contents for Volume 5 Name Reactions in Heterocyclic Chemistry-2 705

Subject Index 709


Chapter 1 Asymmetric Synthesis

Chapter 1 Asymmetric Synthesis

1.1 CBS reduction 1.2 Davis chiral oxaziridine reagents 1.3 Midland reduction 1.4 Noyori catalytic asymmetric hydrogenation 1.5 Sharpless asymmetric hydroxylation reactions

1

2 22 40 46 67

1

2 Name Reactions for Functional Group Transformations

1.1 CBS Reduction

1. I.1 Description The Corey-Bakshi-Shibata (CBS) reduction’ employs the use of borane in conjunction with a chiral oxazaborolidine catalyst to conduct enantioselective reductions of ketones.

This reduction method has a number of advantages that include wide scope, predictable absolute stereochemistry, ready availability of the chiral catalyst in both enantiomeric forms, high yields, experimental ease, recovery of the catalyst (as the amino alcohol), and low cost of goods. The most common form of the chiral oxazaborolidine is derived from prolinol and has a methyl substituent on the boron atom (B-Me-CBS) 1. When one conducts a reduction on a novel system for the first time, this catalyst provides a good compromise of cost, enantioselectivity, and experimental ease. If sufficient control is not observed with this reagent, one can then systematically evaluate the numerous variations of this framework.

he 1

1.1.2 Historical Perspective

2 3 4

The use of optically active borane reagents for asymmetric reductions was first reported by Fiaud and Kagan in 1969.’ These workers used the desoxyephedrine-boron complex 2 as a

Chapter 1 Asymmetric Synthesis 3

reductant. However, the asymmetric induction was very poor and no greater than 5% ee in the reduction of acetophenone was observed. Borch observed similar results employing R- (+)- and S-(-)-a-phenethylamine-borane complexes 33 as the chiral reagent with a variety of ketones.

Continuing on this tack, Grundon and co-workers4 were able to obtain optical purities in the range of 14-22% ee. They achieved this improvement by employing 1 : 1 complexes of leucine methyl ester and diborane 4 in THF. Furthermore, their results were facilitated by the addition of one equivalent of BF3-etherate. Other chiral auxiliaries used include L-valine methyl ester and P-phenylalanine methyl ester.

A major advance in the evolution of chiral boron reagents was reported initially by Itsuno and co-workers in 1981.5 Stereoselectivities up to 73% ee were observed using the 1,3,2-oxazaborolidine derived from p-amino alcohols. Thus (9-valinol 5 in reaction with borane afforded 6 .

5 6

This result sat dormant in the literature until a thorough review of B- and Al-based reductants with chiral auxiliaries was conducted by the Corey group. They were intrigued by the work of Itsuno and began detailed studies of the reaction to understand the mechanistic and stereochemical underpinnings of this reduction reaction. Their efforts resulted in the CBS reduction6 in which improved chiral auxiliaries (7 + 8) were developed and a model was formulated to rationalize the stereochemical outcome of this reaction.

7 a

1.1.3 Mechanism ,J%e great utility of this asymmetric reduction system is a result of the detailed and systematic analysis of its mechanism by the Corey group at Harvard and others.'f9 6* ' Using the Itsuno conditions as a starting point, the Corey laboratories obtained pure (after sublimation) oxazaborolidine 10 from the reaction of amino alcohol 9 with two equivalents of BH3-THF


at 35 "C. The structure of this intermediate was confirmed by FT-IR, 'H and "B NMR, and mass spectroscopy.

9

R

10

A solution of 10 in THF with acetophenone did not effect reduction even after several hours at 23 "C. Rapid reduction (less than one minute) was only observed after the addition of BH3-THF (0.6 equivalents) to afford (R)-1-phenylethanol in 94.7% ee. This stands in contrast to the reduction in the absence of 10 which required much longer reaction times at 23 "C.

Follow-up studies indicated one could reduce the number of equivalents of the oxazaborolidine species to make the process catalytic. With the establishment of this mechanistic foundation, it became possible to rationalize the outcome of this reaction knowing the structure of the catalyst. I'B NMR confirmed the formation of a 1:l complex between 10 and BH3-THF for R = H (ll), while for the species R = Me (11) a single crystal X-ray structure was obtained.8 The &-fused nature of this complex is a result of the concave shape of this bicyclo[3.3.0]octane framework.

10 11

Figure 1 illustrates the 3-dimensional nature of 11. The oxazaborolidine ring forms the horizontal core to this scaffold with the proline-derived five-membered ring forming the P-face back wall. The gem-diphenyl substituents create an additional aspect to the back wall on the p-face and a blocking group on the a-face. The borane moiety complexes to the nitrogen of the heterocyclic ring on the a-face due to the steric interactions it would encounter on the p-face. The only site "open" for a ligand to complex with this catalyst in on the a-face adjacent to the borane group.


Figure 1

The formation of this complex between the pre-catalyst and borane, sets up this system for interaction with the carbonyl group by activating borane as a hydride donor and increasing the Lewis acidity of the endocyclic boron atom. The later effect serves as the point of coordination to the carbonyl oxygen atom. Once this complexation occurs to form 12, the chirality of the scaffold restricts the orientation that the substituents on the carbonyl can adopt. In order to minimize steric interactions with the catalyst, the coordination must occur from the a-face (vide supra) and the small substituent (Rs) must be oriented in the p- face direction to minimize steric interactions with the substituent on the endocyclic boron atom, compared to the large substituent (RL). The consequence of these interactions is to place the hydride equivalent in an o timal position for delivery to the carbonyl carbon atom via a six-membered transition-state! The result of this hydride transfer is 13, in which the carbonyl has undergone a net reduction in an enantiocontrolled fashion. This orientation of the reduction can be predicted based on the relative sizes of the carbonyl substituents and the orientation they must adopt in the transition-state 12. The limited Hammett linear free energy analysis conducted and a measured kinetic isotope effect (kH/kD = 1.7) indicate that both the coordination of the carbonyl compound and the transfer of hydride are probably fast and comparably rate-determining.

11 12 13


The decomposition of intermediate 13 to the isolated alcohol 14 can occur by one of two possible pathways. The first is a net cyclo-elimination that regenerates the catalyst and forms boronate 10.

13 14 10

The alternate pathway occurs by the addition of borane to 13 to form the six- membered BH3-bridged complex 15. This species then decomposes to regenerate the active catalyst 11.

13 15

1.1.4

Figure 2

Variations and Improvements or Modifications

T o - ' . m? * /

97% ee 98% ee 62% ee

. 28%ee 82%ee 67%ee 71% ee

14

76% ee

BH3

11

Bu 55% ee

60% ee

96% ee

Various laboratories, in an effort to improve reaction yield and stereoselectivity, have made targeted modifications on the core structure of the oxazaborolidine catalyst.'h Figure 2 illustrates the level of stereocontrol in the CBS reduction of acetophenone as the R-group was systematically investigated to assess the varying degrees of enantiocontrol. The best


compromise of stereocontrol and synthetic complexity was observed to be the phenyl substituent.

With the heterocyclic substituent optimized, a similar investigation of the B-group

Additional modifications of the framework have included ring size 16, ring fusion 17, was carried out. Examples of the substituents studied are shown in Figure 3.

and ring substitution 18.

n = 1,2,3,4

16 17 18

For example, (-)-P-pinene 19 has been used to construct such a modified catalyst." Oxazaborolidine 21 could be prepare in three steps from the monoterpene and was found to be an efficient catalyst for the reduction of ketones. Thus 22 could be reduced with pre- catalyst 20 and trimethoxyboron to alcohol 23. The chirality of 23 could be rationalized based on the transition-state structure 24.

19 20 21


pre-catalyst

93-98% ee 22 23 24

There are reports that extend the nature of the catalyst beyond an oxazaborolidine framework. One such example made use of a chiral guanidine catalyst." Proline-derived 25 was converted to guanidine 26 in good yield. This species was capable of reducing ketones 27 to alcohols 28 by the addition of BH3-SMe2.

H H

25 26

OH 5 mol%

BH3-SMe2

72-83% ee 78-89% R

28 R

27

29 30

In an attempt to improve the ability to recycle the catalyst, fluorous versions of the oxazaborolidine have been constructed." Pre-catalyst 29 could be prepared in five steps. This species was able to form the requisite chiral catalyst 30 in situ. Ketones 31 could be reduced to alcohols 32 in good to excellent chemical and optical yields. It was noted that aryl


ketones were observed to be more efficient in the reduction process. After the reaction was carried out, the catalyst could be recovered in 99% yield.

10 mol% OH B Hs-TH F

67-93% * R i A b 71-93% ee

31 32

Polymer-bound versions of the oxazaborolidine catalysts have been con~tructed. '~ The linkage to the polymer has been reported on the phenyls of the heterocycle 34 or through a substituent on the nitrogen 36. These polymeric catalysts are recyclable and reuseable without significant loss of activity or selectivity. Placing the linker on the nitrogen appears to create steric interactions that weaken complex formation thus giving rise to diminished enantiocontrol in the reduction. Moving the point of attachment for the resin to the phenyl substituent provided a superior reagent. The reduction of aryl ketones 37 proceeded in good to excellent yields with poor to excellent optical purities in the formation of alcohols 38.

L O Name Reactions for Functlonal Group Transformations

catalyst

2 eq BH3-SMe2 R, R1

57-1 00% 6-95% ee

2 eq NaBH4-TMSCI

37 38

In addition to the reduction of ketones (e.g., aromatic and aliphatic ketones, a-halo ketones, hydroxyketones, enones, and ketoesters), oximes can be reduced to the corresponding amine with this reagent. In general, ketone oxime ethers, such as 39, can give rise to mines 40 in excellent chemical yield with good to excellent optical

Ph Ph

100% S

39 40 69-99% ee

This method was used in the preparation of conformationally constricted analogs of the neurotransmitter glutamate 41, such as (carboxycyclopropy1)glrcines (L-CCG I) 42, that could act as metabatropic glutamate receptor (mGluR) antagonists. Reduction of oxime 43 using the oxazaborolidine derived from prolinol afforded amine 44. Conversion of the furan rings to carboxylic acids afforded the requisite target 42.

41 42

43 44 42

Chapter 1 Asymmetric Synthesis I I

Proline-derived oxazaborolidines 45 have shown to be effective pre-catalysts with triflic acid as an activator to generate cationic Lewis acids.'8915 The optimal proportions of 45 and triflic acid was found to be 1.2: 1. Protonation of 45 produced a 1.5: 1 mixture of 46 and 47 as determined by low temperature 'H NMR. Their interconversion at low temperature (-80 "C) is slow on the NMR timescale. However, this interconversion increases as the temperature rises and at 0 "C this becomes rapid (TJ. Phenyl or o-tolyl were determined to be the best substituents for the R group in 45. For the Ar group of 45, phenyl and 3,5- dimethylphenyl were determined to be optimal.

45 46 47

This in situ formed cationic Lewis acid catalyst coordinates enals in a highly organized fashion (48) that allows for the execution of asymmetric Diels-Alder reactions. Thus for the initially disclosed acrolein examples, the Diels-Alder adducts 51 produced from enals 49 and dienes 50 could be isolated in good to excellent yields with very high optical purities.

48

+' -78 to-95°C /-- R2 58-99%

51 50 91-07% ee 49

The stereochemical outcome from these reactions could be readily rationalized by examining the interactions present in 48. The [3.3.0]bicyclic system provided a rigid convex scaffold that only allowed the enal to coordinate from the more exposed face of this


molecule. The carboxaldehyde hydrogen forms an H-bonding interaction with the endocyclic oxygen atom of the heterocyclic scaffold thus only allowing the diene to approach from the periphery of the complex.

An extension to enones has been accomplished but opposite face selectivities were observed. To rationalize this result, an alternate transition-state structure 52 was formulated. Single crystal X-ray structure analysis examining the coordination of BF~etherate with enones and enoates was used to provide support for this novel mode of complexation.

52

Catalysts derived from triflic acid decompose at appreciable rates at or above 0 "C, which limits the utility of these reagents in Diels-Alder reactions. Switching to triflimide as the acid source resulted in protonation of 45 to produce 53.16 'H NMR from -80 to 23 "C showed the formation of three species including 53 and two diastereomeric tetracoordinated boron species in a ratio of 1 : 1.2. Additionally, 53 was found to have greater thermal stability and superior catalytic efficiency compared to 46/47 for less reactive dienes. This was illustrated in the Diels-Alder reaction of 54 with 55 to produce adduct 56.


This last observation was capitalized on by the Corey labs in their efficient synthesis of Tamiflu@ (oseltamivir) 59. The emergence of the virulent strain of influenza, H5N1, coupled with the lack of supply due to the current synthetically challenging route, highlighted the need for such reagents that allow for the rapid and efficient construction of difficult targets. The reaction could be conducted on a multigram scale of 57 and 55 to generate sufficient quantities of the Diels-Alder adduct 58 to complete the target 59."

10 mol%

23 "C 30 h

0

+ / i 1 0 C H 2 C F 3 7 ~ ' ~ t c o I C H 2 c F 3

97% 0 H2P04 >97% ee

57 55 58 59

Follow-up work by other groups examined alternate sources of generating Lewis acids from various oxazaborolidines (60 + 61)'' One report scanned the commonly used metal halides and found tin tetrachloride to be the best when coupled to valinol-based oxazaboroline. Thus, cyclopentadiene 61 reacting with methacrolein 63 using such a catalyst afforded the Diels-Alder adduct 64 in excellent yield and excellent optical purity.

60 61

1 mol% C02CHzCF3

SnCI4 1 mol%

2 h 99%

95% ee

-78 o c

62 63 64

Rather than accessing the chiral pool via amino acid precursors for CBS catalysts, the (R,R)- and the (S,S)-sulfonamide derivatives of 1 ,Z-diphenyl- 1 ,Zdiaminoethane


(stilbenediamine, stien) 66 in complex with boron 65 or aluminum 67 have also been applied to the Diels-Alder rea~t ion . ’~

Ph Ph Ph *MYh .)+? d c-

RSO;~.~J-SO,R RS02,N H H N‘S02R R S O ~ - - ~ \ + ~ ~ - S O ~ R

X X

65 66 67

The use of these reagents was exemplified in the preparation of an advanced intermediate in the synthesis of prostaglandins 71. Diene 68 and dienophile 69 were allowed to undergo the Diels-Alder reaction catalyzed by a derivative of 67 to afford adduct 70.l9 This intermediate was subsequently transformed into 71, a well-known precursor in the synthetic preparations of prostaglandins.

PhY-tph BnO 68 CFlS02”. ,“SOf2FI

+ ?‘ Me

96%

94% ee HO

70 71 0 69

The Lewis acidic nature of these catalysts has permitted their extended use in the Mukaiyama aldol reaction. In this application of CBS reagents, one such example involved the condensation of ketene acetals 72 with aldehydes 73 to produce adducts 74.*’

hoTMs + RCHO 6 8 4 7 % ALSO2 n R H g O E t

OEt 84-98% ee 72 73 74

In a similar manner, the insect attractant endo-l,3-dimethyl-2,9- dioxabicyclo[3.3. Ilnonane 78 could be prepared?’ To this end, masked keto aldehyde 75

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Name Reactions for Functional Group Transformations...The more complex functional groups, formed using additional elements or by concatenation of simpler groups, play a similar unifying