Applications of Transition Metal Catalysis in Drug Discovery and Development: An Industrial Perspective

Lays the groundwork for developing promising new drugcandidates

Drawing on real–life examples, this book demonstrates theapplications of transition metal catalysis in drug discovery anddevelopment, and its role in the efficient creation of bothpreclinical and clinical drug candidates as well as commercializeddrugs. The authors pay particular attention to the challenges oftransitioning reactions developed in academic labs into scalableindustrial processes.

Applications of Transition Metal Catalysis in Drug Discoveryand Development begins with a general overview of the use oftransition metal catalysis in the pharmaceutical industry. Next, itcovers:

Transition metal–catalyzed carbon carbon cross–couplingreactions Palladium– and copper–catalyzed carbon heteroatomcross–coupling reactions Asymmetric cross–coupling reactions and metathesis Transition metal–catalyzed synthesis of five– and six–memberedheterocycles Oxidative catalysis and industrial asymmetrichydrogenation

Both the editors and authors are internationally recognizedexperts in drug discovery and development. All authors arescientists from such major pharmaceutical companies as BoehringerIngelheim, GlaxoSmithKline, Merck, Amgen, and Novartis.Additionally, many of the authors have been responsible fordeveloping the reactions and the drugs discussed in the book,providing readers with firsthand accounts of their discoveries.

This remarkable work serves as a guide, historical perspective,and practical compendium, offering pharmaceutical researchers andmedicinal chemists a unique perspective on the applications oftransition metal catalysis in drug discovery and development.Moreover, the book lays the groundwork for continued development oftransition metal–catalyzed processes, setting the stage for new andpromising drug candidates.

Preface vii

Contributors ix

About the Authors xi

1 Transition Metal Catalysis in the Pharmaceutical Industry1
Carl A. Busacca, Daniel R. Fandrick, Jinhua J. Song, and ChrisH. Senanayake (Boehringer Ingelheim Pharmaceuticals)

2 Selected Applications of Transition Metal–CatalyzedCarbon Carbon Cross–Coupling Reactions in the PharmaceuticalIndustry 25
Hong C. Shen (Roche)

3 Selected Applications of Pd– and Cu–CatalyzedCarbon Heteroatom Cross–Coupling Reactions in thePharmaceutical Industry 97
Jingjun Yin (Merck)

4 Asymmetric Cross–Coupling Reactions 165
Vince Yeh (Novartis) and William A. Szabo (Consultant in DrugDevelopment)

5 Metathesis Reactions 215
Oliver R. Thiel (Amgen)

6 Transition Metal–Catalyzed Synthesis of Five– and Six–MemberedHeterocycles 257
Cheol K. Chung (Merck) and Matthew L. Crawley (Main LineHealth)

7 Oxidative Catalysis 277
Lamont Terrell (GlaxoSmithKline)

8 Industrial Asymmetric Hydrogenation 315
Hans–Ulrich Blaser (Solvias)

Index 343

MATTHEW L. CRAWLEY, PhD, is the Director of the CommunityPhysician Electronic Medical Records Program at Main Line Health.Previously, he has worked as a medicinal chemist at Pfizer andWyeth Research. Dr. Crawley is an author of more than twentypublications, and his discoveries have resulted in severalpatents.

BARRY M. TROST, PhD, is Tamaki Professor of Humanitiesand Sciences in the Department of Chemistry at Stanford University.Dr. Trost has been elected a Fellow of the American Academy ofSciences and member of the National Academy of Sciences. He hasserved as chairman of the NIH Medicinal Chemistry Study Section,held over 120 university lectureships, and presented over 260plenary lectures at national and international meetings.

The book will be particularly appreciated by youngscientists, especially those aspiring to a future in thepharmaceutical industry, because it shows what kind of problemsthey will be asked to solve once they start their industrialcareer.   (ChemMedChem, 1 March 2013)

All chapters are well–written and comprehensive with lotsof examples from OPR and D.  The book is highly recommended toall process chemists.   (Organic Process Research& Development Journal, 1 November 2012)