Robert E. Gawley - Principles of Asymmetric Synthesis, 2E

Dieter Seebach

Chirality in chemistry and asymmetric synthesis (chemical reactions, in which elements of chirality are generated) have developed from a specialty pursued by outsiders (chiromaniacs) to an art cultured by some learned ones, and now are part of essentially every chemists daily life. We should, however, not forget that in a multistep synthesis the transition from achiral intermediates or from racemic mixtures to enantiopure intermediates is unique. In all of the other steps, it is functional-group selectivity, regio- and diastereoselectivity that are at stake.

The development of asymmetric synthesis has taken place exponentially in the last three decades, triggered by a number of circumstances. Many more chemists are intrigued and attracted by the phenomenon of chirality and by the origin of homochirality of the molecules of life. Practitioners of organic synthesis and synthetic methodology have annexed transition-metal chemistry (with chiral ligands on the metals) and biologicalchemical transformations to achieve enantioselective catalysis. Concomitantly, new chromatographic and spectroscopic methods for determining enantiomer ratios have facilitated the ease and accuracy of analyses of products of enantioselective reactions. Perhaps the strongest driving force for the development was the necessity of producing pharmaceuticals, diagnostics, vitamins, and agrochemicals in enantiopure form (their biological targets are chiral, after all!).

As I stated in the foreword of the first edition in 1996, the authors of Principles of Asymmetric Synthesis have managed to cover the subject in a condensed and masterly way; they have chosen well-defined topics for the eight chapters of the book; they have used clear-cut concepts and concise chemical language for the presentations; they have discussed mechanistic considerations with due care; they have included a glossary of stereochemical terms (those to use and those not to use!); they have provided extensive referencing. All of this is still true for the second edition, which has grown from 372 to 556 pages, with an almost doubling of references from ca. 1300 to 2400. This is not due to just adding more of the same but mostly due to including the dramatic new developments that have occurred in the past 15 years.

This can be seen as a realization of two dreams, expressed in 1990 by an organic chemist

As far as the first dream is concerned, there has been a revival of what was called, in 1935, organocatalysis , i.e. catalysis of the classical, main-group organic transformations without involvement of metals or metal ions, using chiral amino compounds, carbenes, Brnsted acids, counter ions, ureas, or HMPA derivatives as catalysts for essentially all the well-known workhorse reactions of organic synthesis, such as aldol, Michael, DielsAlder, 1,3-dipolar additions, hydride transfer from Hantzsch ester, Mannich, Strecker, Stetter, BaylisHillman reactions, -alkylation and -functionalization of carbonyl compounds, FriedelCrafts-type reactions, epoxidations, and aziridinations, to name only a few.

The second dream concerns new types of miracle reactions catalyzed by transition metals that enable the synthetic chemist to perform often incredibly complex transformations in one step, which were undreamed of by experts of classical organic reactions; three Nobel prizes have been awarded in this field in the past decade (2001, 2005, and 2010). A plethora of chiral ligands has become available for enantioselective versions of most of these reactions.

Indeed, inclusion of sections covering organocatalysis (in (dioxiranes, sulfoxidations, BaeyerVilliger and BeckmanSchmidt type reactions).

The second edition of Principles of Asymmetric Synthesis is up-to-date in all aspects of this important part of organic synthesis. Of special note, the first two chapters on Introduction, General Principles, and Glossary of Stereochemical Terms and Practical Aspects of Asymmetric Synthesis are unique among all the books I have seen on stereochemistry. This book can serve as a textbook for classes, as a monograph on enantio- and diastereoselective synthesis, and as a reference work to find seminal publications, even for the expert in the field.