From a Chiral Switch to a Ligand Portfolio for Asymmetric Catalysis

Hans-Ulrich Blaser carried out his doctoral research with Prof. Eschenmoser at the ETH in Zürich, where he received his Ph.D. degree in 1971. Between 1971 and 1975, he held postdoctoral positions at the University of Chicago (J. Halpern), Harvard University (J. A. Osborn), and Monsanto (Zürich). During 24 years at Ciba-Geigy (1976–1996) and Novartis (1996–1999), he gained practical experience in R&D in the fine chemicals and pharmaceutical industry. At Solvias, he is presently chief technology officer. His main interests are the study and industrial application of selective catalysts. During his industrial carrier, he has developed and implemented numerous catalytic routes for agrochemicals, pharmaceuticals, and fine chemicals (both as a project leader and section head).

Benoît Pugin studied chemistry at the ETH in Zürich and carried out his Ph.D. thesis with Prof. Venanzi in the field of metal organic chemistry and homogeneous catalysis. In 1982, he moved to Ciba-Geigy for a postdoctoral period, and since 1983, he has been working in the catalysis research group of Ciba-Geigy/Novartis and now as a leading scientist with Solvias. He has worked in the fields of sonochemistry, catalyst immobilization, enantioselective hydrogenation, and catalytic oxidation. Today, his main activity is the development of new chiral ligands for enantioselective catalysis.

Felix Spindler did his doctoral research on homogeneous catalysis with Prof. Pino at the ETH in Zürich, where he received his Ph.D. degree in 1981. In 1983, he joined Ciba-Geigy in Basel and gained practical experience in R&D related to the application of homogeneous asymmetric catalysis in the fine chemicals and pharmaceutical industry, which continued at Novartis (1996–1999) and Solvias. During his industrial carrier, he has developed and implemented numerous catalytic routes for agrochemicals, pharmaceuticals, and fine chemicals. He presently holds a position as leading scientist in the field of homogenous enantioselective hydrogenation.

Marc Thommen obtained his Ph.D. degree in 1995 from the University of Bern working with Prof. R. Keese. He spent 2 years as a postdoctoral researcher at Stanford University with Prof. B. M. Trost and joined the catalysis group of Novartis in 1998 as project leader for the development of catalytic processes. At Solvias, he was instrumental in the development of a comprehensive ligand portfolio. He was appointed product manager for chiral ligands and catalysis services. Presently, he holds the position of a senior project leader at DSM Nutritional Products, Switzerland.

This Account is divided into two sections. In the first section, the development of an enantioselective manufacturing process for ( S)-metolachlor, the active ingredient of the grass herbicide Dual Magnum, is described. This is today’s largest application of asymmetric catalysis, and the Ir-Xyliphos hydrogenation catalyst achieves unprecedented 2 millions turnovers. The development started in 1982 and ended when the first production batch was run in November 1996. The strategies and approaches used for attaining the elusive goal are described, and the lessons learned are discussed. In the second section, the development and performance of a portfolio of chiral diphosphines for industrial asymmetric applications are described. Central to the portfolio is the idea of modular ligand families, i.e., diphosphines with the same backbone, where steric and electronic properties are easily tuned by the choice of the substituents at the phosphorous atoms.