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Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions

Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions

Hans Ulrich Blaser (Editor), Elke Schmidt (Editor)

ISBN: 978-3-527-60577-4 February 2007 480 Pages




Edited by two of the experts in the field, the central aim is to show organic chemists working in process development that enantioselective catalysis is suitable for the large-scale production of enantioenriched intermediates. In so doing, it is equally a source of information and inspiration for academic research, and, with its contribution by Noble prizewinner W. S. Knowles, will also heighten the status of industrial catalyst specialists working in the exciting field of enantioselective catalysis.
Some 25 contributions from top industrial researchers around the world present case studies on the development of the widest possible range of large-scale enantioselective processes, featuring stereoselective production processes of fine-chemicals, agrochemicals and pharmaceuticals. Clearly structured according to the nature of the task, this handbook adopts a problem-driven approach such that readers can easily find how colleagues have dealt with a similar situation.
List of Contributors.

Introduction (Hans-Ulrich Blaser & Elke Schmidt).


1. Asymmetric Hydrogenations— The Monsanto L-Dopa Process (William S. Knowles).

2. The Other L-Dopa Process (Rüdiger Selke).

3. The Chiral Switch of Metolachlor: The Development of a Large-Scale Enantioselective Catalytic Process (Hans-Ulrich Blaser, et al.).

4. Enantioselective Hydrogenation: Towards a Large-Scale Total Synthesis of (R,R,R)-a-Tocopherol (Thomas Netscher, et al.).

5. Comparison of Four Technical Synthesis of Ethyl (R)-2-Hydroxy-4-Phenylbutrate (Hans-Ulrich Blaser, et al.).

6. Biocatalytic Approaches for the Large-Scale Production of Asymmetric Synthons (Nicholas M. Shaw, et al.).

7. 7-Aminocephalosporanic Acid-Chemical Versus Enzymatic Production Process (Thomas Bayer).

8. Methods for the Enantioselective Biocatalytic Pro duction of L-Amino Acids on an Industrial Scale (Harald Gröger & Karlheinz Drauz).


1. The Large-Scale Biocatalytic Synthesis of Enantiopure Cyanohydrins (Peter Poechlauer, et al.).

2. Industrialization Studies of the Jacobsen-Hydrolytic Kinetic Resolution of Epichlorohydrin (Larbi Aouni, et al.).

3. Scale-up Studies in Asymmetric Transfer Hydrogenation (John Blacker & Juliette Martin).

4. Practical Applications of Biocatalysis for the Manufacture of Chiral Alcohols such as (R)-1,3-Butanediol by Stereospecific Oxidoreduction (Akinobu Matsuyama & Hiroaki Yamamoto).

5. Production of Chiral C3 and C4 Units via Microbial Resolution of 2,3-Dichloro-1-propanol, 3-Chloro-1,2-propanediol and Related Halohydrins (N. Kasai o& T. Suzuki).


1. Synthesis of Unnatural Amino Acids (David J. Ager & Scott A. Laneman.).

2. The Application of DuPHOS Rhodium(I) Catalysts for Commercial Scale Asymmetric Hydrogenation (Christopher J. Cobley, et al.).

3. Liberties and Constraints in the Development of Asymmetric Hydrogenations on a Technical Scale (John F. McGarrity, et al.).

4. Large-Scale Applications of Biocatalysis in the Asymmetric Synthesis of Laboratory Chemicals (Roland Wohlgemuth).


1. Development of an Efficient Synthesis of Chiral 2-Hydroxy Acids (Junhua Tao & Kevin McGee).

2. Factors Influencing the Application of Literature Methods Toward the Preparation of a Chiral trans-Cyclopropane Carboxylic Acid Intermediate During Development of a Melatonin Agonist (Ambarish K. Singh, et al.).

3. Hetero Diels-Alder-Biocatalysis Approach for the Synthesis of (S)-3-[2-{(Methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol Methanesulfonate: Successful Application of an Enzyme Resolution Process (Jean-Claude Caille, et al.).

4. Multi-Kilo Resolution of XU305, a Key Intermediate to the Platelet Glycoprotein IIb/IIIa Receptor Antagonist Roxifiban Via Kinetic and Dynamic Enzymatic Resolution (Jaan A. Pesti & Luigi Anzalone).

5. Protease-Catalyzed Preparation of (S)-2-[(tert-Butylsulfonyl)methyl]-hydrocinnamic Acid for Renin Inhibitor RO0425892 (Beat Wirz, et al.).

6. Protease-Catalyzed Preparation of Chiral 2-Isobutyl Succinic Acid Derivatives for Collagenase Inhibitor RO0319790 (Beat Wirz, et al.).

7. An Innovative Asymmetric Sulfide Oxidation: The Process Development History Behind the New Antiulcer Agent Esomeprazole (Hans-Jürgen Federsel & Magnus Larsson).

8. Development of a Biocatalytic Process for the Resolution of (R)- and (S)-Ethyl-3-amino-4-pentynoate Isomers Using Enzyme Penicillin G Amidohydrolase (Ravindra S. Topgi).

Subject Index.

"I highly recommend this book to all organic chemists in industry and academia, but particularly those in development and production. Not only is it an excellent reference work, it is also a thumping good read!"

Peter Spargo, Organic Process Research & Development

"This book is a must for process developers, and is of interest to both chemists and biochemists...Moreover, the book is easy and relaxing to read, and the variety of topics invites browsing."

"Dieses Buch ist ein "Muss" für Prozessentwickler, wobei nicht nur Chemiker, sondern auch Biochemiker angesprochen sind...Daneben läßt sich das Buch auch "einfach so" gut lesen, die Vielfalt der Themen lädt geradezu zum Schmökern ein!"

Rainer Stürmer, BASF AG, Ludwigshafen
Angewandte Chemie + IE 20/04