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Catalytic Asymmetric Synthesis


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to Catalytic Asymmetric Synthesis and advance it to the new height.

      Takahiko Akiyama

      Iwao Ojima

      November, 2021

      Biological systems, in most cases, recognize a pair of enantiomers as different substances, and the two enantiomers will elicit different responses. Thus, one enantiomer may act as a very effective therapeutic drug, whereas the other enantiomer is highly toxic. The sad example of thalidomide is well‐known. It is the responsibility of synthetic chemists to provide highly efficient and reliable methods for the synthesis of desired compounds in an enantiomerically pure state, that is, with 100% enantiomeric excess (% ee), so that we shall not repeat the thalidomide tragedy. It has been shown for many pharmaceuticals that only one enantiomer contains all of the desired activity, and the other is either totally inactive or toxic. Recent movements of the Food & Drug Administration (FDA) in the United States clearly reflect the current situation in “Chiral Drugs,” that is, pharmaceutical industries will have to provide rigorous justification to obtain the FDA’s approval of racemates. Several methods are used to obtain enantiomerically pure materials, which include classical optical resolution via diastereomers, chromatographic separation of enantiomers, enzymic resolution, chemical kinetic resolution, and asymmetric synthesis.

      The importance and practicality of asymmetric synthesis as a tool to obtain enantiomerically pure or enriched compounds have been fully acknowledged to date by chemists in synthetic organic chemistry, medicinal chemistry, agricultural chemistry, natural products chemistry, pharmaceutical industries, and agricultural industries. This prominence is due to the explosive development of newer and more efficient methods during the last decade.

      This book describes recent advances in catalytic asymmetric synthesis with brief summaries of the previous achievements as well as general discussions of the reactions. A previous book reviewing 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 Nijhoff, 1986) also concisely covers contributions up to early 1984. In 1971, an excellent book, Asymmetric Organic Reactions, by J. D. Morrison and H. S. Mosher, reviewed all earlier important work on the subject and compiled nearly 850 relevant publications through 1968, including some papers published in 1969. In the early 1980s, a survey of publications dealing with asymmetric synthesis (in a broad sense) indicated that the total number of papers in this area of research published in the 10 years after the Morrison/ Mosher book, that is, 1971–1980, was almost the same as that of all the papers published before 1971. This doubling of output clearly indicates the attention paid to this important topic in 1970s. Since the 1980s, research on asymmetric synthesis has become even more important and popular when enantiomerically pure compounds are required for the total synthesis of natural products, pharmaceuticals, and agricultural agents. It would not be an exaggeration to say that the number of publications on asymmetric synthesis has been increasing exponentially every year.

      This book covers the following catalytic asymmetric reactions: asymmetric hydrogenation (Chapter 1), isomerization (Chapter 2), cyclopropanation (Chapter 3), oxidations (epoxidation of allylic alcohols as well as unfunctionalized olefins, oxidation of sulfides, and dihydroxylation of olefins) (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 (Chapter 9). The authors of the chapters are all world leaders in this field, who outline and discuss the essence of each catalytic asymmetric reaction. In addition, a convenient list of the chiral ligands appearing 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 all levels in both academic and industrial laboratories.

      Iwao Ojima

      March, 1993

      Lutz Ackermann, Institut für Organische und Biomolekulare Chemie, Georg‐August‐Universität Göttingen, Göttingen, Germany and Wöhler Research Institute for Sustainable Chemistry (WISCh), Georg‐August‐Universität Göttingen, Göttingen, Germany

      Takahiko Akiyama, Department of Chemistry, Gakushuin University, Tokyo, Japan

      Andrés R. Alcántara, Department of Chemistry in Pharmaceutical Sciences, Section of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain

      Thorsten Bach, School of Natural Sciences, Department Chemie and Catalysis Research Center (CRC), Technische Universität München, Garching, Germany

      Eva Bednárˇová, Department of Chemistry, Columbia University, New York, NY, USA

      Jun Kee Cheng, Department of Chemistry, Southern University of Science and Technology, Shenzhen, China

      Aurélie Claraz, Institut de Chimie des Substances Naturelles, Université Paris Saclay, Gif‐sur‐Yvette, France

      Uttam Dhawa, Institut für Organische und Biomolekulare Chemie, Georg‐August‐Universität Göttingen, Göttingen, Germany

      Yun E. Du, California Institute of Technology, Pasadena, CA, USA

      Jorge Escorihuela, Department of Organic Chemistry, Pharmacy Faculty, University of Valencia, Valencia, Spain

      Tyler J. Fulton, California Institute of Technology, Pasadena, CA, USA

      Santos Fustero, Department of Organic Chemistry, Pharmacy Faculty, University of Valencia, Valencia, Spain

      Luo