Fundamentals of Asymmetric Catalysis

Patrick J. Walsh 
Marisa C. Kozlowski

University of Pennsylvania


FOREWORD

It is a pleasure to provide a foreword to this monograph entitled the Fundamentals of Asymmetric Catalysis.

In reviewing this text, I am reminded of an earlier landmark monograph, Asymmetric Organic Reactions written by Morrison and Moser. This text, published in 1971, appeared at a time when few chemists were engaged in the development of enantioselective processes. In fact, not a single non-enzymic enantioselective process was even discussed at that time. As a young academician, I read this treatise with great interest; however, I was slow in getting the message! In the intervening 37 years the field of asymmetric catalysis has emerged as one of the principal activities of reaction development! It is my projection that the Walsh & Kozlowski monograph will become the "Bible" for those who wish to master the concepts that are the underpinnings to the research advances in the area of asymmetric catalysis. The chapters are arranged by topic, not reactions, and provide a solid foundation of the concepts in asymmetric catalysis. Nonetheless, the reader is exposed to many reaction types. The authors have also done an excellent job at integrating metal catalyzed reactions with organocatalysis.

The first chapter deals with "Modes of Asymmetric Induction." The discussion integrates simple resolution, kinetic resolution, and the application of the Curtin-Hammett Principle in a series of case studies. Both metal- and organo-catalysts are nicely integrated into the discussion.

The second chapter deals with "Lewis Acid and Lewis Base Catalysis." This chapter covers both of these important topics in a balanced fashion. Again, all forms of catalysis are covered.

Chapter three, "Beyond Lewis Acid and Lewis Base Catalyzed Activation," provides a discussion of chiral cations and anions along with a treatment of organo-catalysts that rely on H-bonding organizational principles. Other topics include group transfer catalysis, alkene metathesis, and alkene activation by pi-coordination. This discussion represents an important catch-all of topics needed in the ensuing discussion

In Chapter four, "Asymmetric Induction in Enantioselective Catalysis," the fundamental issues of asymmetric induction are presented, again illustrated with current examples from the literature. A general discussion of the transmission of asymmetry, ligand architecture, and the importance of the trans influence are covered.

In Chapter five, "Nonclassical Two-Point Catalyst Substrate Interactions," catalysts based on the pairing of a primary (Lewis acid) with a secondary weak interaction are discussed. This secondary interaction includes H-bonding, and pi-stacking organizational interactions. In many of the cases in this chapter, the nature of the secondary catalyst-substrate is still under active debate. The reader is presented with the facts. Conclusions will follow in due course.

Chapter six addresses alternative approaches to asymmetric catalysis, including chiral poisoning, chiral activation, and chiral catalyst optimization by modification of achiral ligands.

In Chapters seven–nine, a concise discussion of kinetic, parallel kinetic, and dynamic kinetic resolution is presented along with a host of case studies.

Chapter ten, "Desymmetrization Reactions," addresses the fundamental concepts associated with enantioselective desymmetrization. Topics from earlier chapters are integrated into this monologue.

In Chapter eleven, the authors address the issue of non-linear effects. This important chapter ultimately contributes to an enhanced understanding of reaction mechanism as the investigation of non-linear effects is now a routine exercise that is incorporated into the presentation of a catalysis model.

Chapter twelve, "Bifunctional, Dual, and Multifunctional Catalyst Systems," addresses the combined effects of many of the individual catalytic principles presented in earlier chapters. This integration of the individual concepts is one of the principal strengths of this treatise.

This monograph could easily have been terminated at this point as the fundamental principles of asymmetric catalysis have been thoroughly covered. Nonetheless, succeeding chapters including, "Double Stereo-differentiating Processes;" "Multistep Asymmetric Catalysis," "Supported Chiral Catalysts," and "Applications of Asymmetric Catalysis in Synthesis," are included along with critical discussions.

Imagine yourself as a professor who is faced with presenting a topical course in asymmetric catalysis. This task is currently not a trivial undertaking since there is no integrated discussion of the various topics one might wish to cover. This monograph, provides the intellectual framework for a detailed discussion of the intricacies of catalytic processes and assists its readership in providing a strong bridge to the primary scientific literature. The discussion nicely tracks the intellectual perspective between that of a text and a monograph.

I predict that this monograph will be widely used as a text in advanced courses and a primary reference text for the research scientist. The authors are to be congratulated for their accomplishment.

David A. Evans
Professor of Chemistry
Harvard University