Applications of Transition Metal Catalysis in Drug Discovery and Development

This book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs.  The authors pay particular attention to the challenges of transitioning academically-developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development – it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.

Preface vii Contributors ix About the Authors xi 1 Transition Metal Catalysis in the Pharmaceutical Industry 1 Carl A. Busacca, Daniel R. Fandrick, Jinhua J. Song, and Chris H. Senanayake (Boehringer Ingelheim Pharmaceuticals) 2 Selected Applications of Transition Metal-Catalyzed Carbon–Carbon Cross-Coupling Reactions in the Pharmaceutical Industry 25 Hong C. Shen (Roche) 3 Selected Applications of Pd- and Cu-Catalyzed Carbon–Heteroatom Cross-Coupling Reactions in the Pharmaceutical Industry 97 Jingjun Yin (Merck) 4 Asymmetric Cross-Coupling Reactions 165 Vince Yeh (Novartis) and William A. Szabo (Consultant in Drug Development) 5 Metathesis Reactions 215 Oliver R. Thiel (Amgen) 6 Transition Metal-Catalyzed Synthesis of Five- and Six-Membered Heterocycles 257 Cheol K. Chung (Merck) and Matthew L. Crawley (Main Line Health) 7 Oxidative Catalysis 277 Lamont Terrell (GlaxoSmithKline) 8 Industrial Asymmetric Hydrogenation 315 Hans-Ulrich Blaser (Solvias) Index 243