Asymmetric Organocatalysis - From Biomimetic Concepts to Applications in Asymmetric Synthesis
Albrecht Berkessel, Harald Gröger
Hardcover, 440 Pages
First Edition, 2005
Asymmetric catalysis represents still one of the major challenges in modern organic chemistry. Besides the well-established asymmetric metal-complex-catalysed syntheses and biocatalysis, the use of "pure" organic catalysts turned out to be an additional efficient tool for the synthesis of chiral building blocks. In this handbook, the experienced authors from academia and industry provide the first overview of the important use of such metal-free organic catalysts in organic chemistry. With its comprehensive description of numerous reaction types, e.g., nucleophilic substitution and addition reactions as well as cycloadditions and redox reactions, this book targets organic chemists working in industry and academia, and deserves a place in every laboratory.
The enantioselective production of compounds is a central theme in current research. A diverse arsenal of metal-based and biocatalytic methods stands ready to deploy, but with concerns about cost, availability and the toxicity of the catalysts, and faced with laborious process development work, chemists still seek to have additional alternative methods to select from. For a long time, little attention has been given to the field of organocatalysts, metal-free compounds predominantly composed of C, H, O, N, S and P. Although the first enantioselective organocatalytic reactions had already been described at the beginning of the 20th century, the transition metal-based catalysts developed more recently have drawn the lion’s share of attention.
The advantages of organocatalysts include their lack of sensitivity to moisture and oxygen, and their ready availability, low cost, and low toxicity, which confers a huge direct benefit in the production of pharmaceutical intermediates when compared with transition metal catalysts. The first publications from the groups of MacMillan, List, Denmark, and Jacobson paved the way in the year 1990. These reports introduced highly enantioselective transformations that rivaled the metal-catalyzed reactions in both yields and selectivity. Once this foundation was laid, mounting interest in organocatalysis was reflected in a rapid increase in publications on this topic from a growing number of research groups. The first monograph to provide an overview of the field has now appeared, "Asymmetric Organocatalysis - From Biomimetic Concepts to Applications in Asymmetric Synthesis".
In this reviewer’s opinion, the authors Albrecht Berkessel and Harald Gröger have arrived at a treatment that is elegantly balanced between the introduction, general explanations and reaction examples from the current literature. Their explanations of the principles of organocatalysis are easily understood, and these are followed by chapters that cover important reaction types, e.g. nucleophilic addition to carbonyls. These chapters also begin with an introduction, and proceed logically through a historical survey of older methods leading up to the most current reactions. Several reaction mechanisms are explained in detail, and it is noteworthy that the majority of the reactions are illustrated with actual examples that provide the reader with a clear sense of the scope of possible substrates. An appendix presents the reader with a number of typical organocatalysts and the range of their applications that have been described to date. This compilation contains a veritable basis set of inexpensive screening candidates for use in reactions yet to be described.
The straightforward organization of the book and detailed discussions of individual reactions makes it particularly worthwhile for students and chemists who have an interest in the field of organocatalysis. With its focus on the most important, basic reactions of organic chemistry, this work is also a must for serious research libraries.
General Mechanistic Considerations
Nucleophilic Substitution at Aliphatic Carbon
Nucleophilic Addition to Electron-deficient C=C Double Bonds
Nucleophilic Addition to C=N Double Bonds
Nucleophilic Addition to C=O Double Bonds
Nucleophilic Addition to Unsaturated Nitrogen
Protonation of Enolates and Tautomerization of Enols
Reduction of Carbonyl Compounds
Kinetic Resolution of Racemic Alcohols and Amines
Desymmetrization and Kinetic Resolution of Anhydrides
Appendix: Tabular Survey of Organo-Catalysts, Synthesis and Application