Industrial-Scale Synthesis and Applications of Asymmetric Hydrogenation Catalysts

Nicholas B. Johnson was born in Swindon, U.K., in 1969. He obtained his B.Sc. degree in chemistry from the University of Manchester Institute of Science and Technology (UMIST) in 1991, remained at UMIST working with Prof. Richard Stoodley studying the preparation of peptidomimetics of potential therapeutic interest, and obtained his Ph.D. degree in 1994. Joining Chiroscience in 1994, initially as a research chemist, he has subsequently moved into business development roles and was awarded an M.B.A. from Imperial College London in 2005. His main focus is now on the commercial development and marketing of Dowpharma’s asymmetric catalytic technologies, primarily for use in the pharmaceutical industry.

Ian C. Lennon was born in Lisburn, Northern Ireland, in 1963. He graduated from the University of St. Andrews in 1985 with a B.Sc. degree in chemistry and then worked for Merck, Sharp & Dohme Harlow, Essex, in drug discovery. In 1989, he left Merck to study for a Ph.D. degree with Steve Ley at Imperial College, London. In 1993, Ian joined Chiroscience, and in 1995, he carried out a secondment with Barry Trost at Stanford University to evaluate his palladium(0)-catalysed asymmetric allylic alkylation technology. In 2000, Ian’s responsibilities were extended to include management of the chemocatalysis core research team. Chirotech was acquired by The Dow Chemical Company in 2001 and is now part of Dowpharma. Ian is currently a Scientist and Technology leader for Chemocatalysis and is involved with the development of asymmetric chemocatalysis capability, promotion of chiral technology, and management of customer projects. Ian is an Editorial Advisory Board member of Organic Process Research & Development and Chimica Oggi.

Paul H. Moran was born in 1972 in Paisley, Scotland. He obtained a B.Sc. degree in chemistry from the University of Strathclyde, where he worked with Prof. Peter L. Pauson on the synthesis of jasmonoid compounds via the cobalt-mediated Pauson–Khand reaction. He was awarded the title of Dr rer nat from the Technische Universität Berlin in 1998 while investigating the photochemical reactions of organorhodium complexes under the supervision of Prof. Jörn Müller. After a brief postdoctoral spell, working in the field asymmetric organomagnesium chemistry, with Prof. Kenneth W. Henderson and Prof. William J. Kerr, he took up his current position in Chirotech (now Dowpharma). His main interests revolve around the commercial production of chiral ligands and catalysts for the use in asymmetric processes for the pharmaceutical industry.

Jim Ramsden was born in Leeds in 1963. After obtaining his B.Sc., M.Sc., and Ph.D. degrees from the University of Sheffield, he held postdoctoral placements with Prof. John A. Gladysz in Utah, studying the use of chiral organometallic complexes and metal/metal-supported carbon chains, and with Dr. John M. Brown at Oxford, studying mechanistic aspects of rhodium-catalysed asymmetric hydrogenation. Having worked for Zeneca and Avecia, he moved to Chirotech (now Dowpharma) in 1998. His research interests are in the application of chiral organometallic compounds as synthetic templates and in the discovery and application of catalytic asymmetric processes.

This Account provides an overview of our activities in the area of asymmetric hydrogenation over the last 12 years. We discuss the manufacture of metal-containing precatalysts and their use in asymmetric hydrogenation processes. Many of the metal complexes have been made on a multikilogram scale for our own use and also provided to our customers. In addition, we review some of the applications that we have developed for our asymmetric hydrogenation catalysts, many of which have been operated on commercial scales. This all underlines that asymmetric hydrogenation is a mature technology that has been adopted for use in the pharmaceutical and fine-chemical industries.