The Chiral Switch of Metolachlor: The Development of a Large-Scale Enantioselective Catalytic Process

Abstract

The development of an enantioselective catalytic process for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-metolachlor (trade name Dual Magnum^®). Four synthetic routes were investigated in some detail. The key step for the technical process of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate made possible by a new iridium ferrocenyl diphosphine catalyst system. Using optimized conditions, the isolated imine can be hydrogenated at a hydrogen pressure of 80 bar and 50°C with a substrate-to-catalyst ratio of >1'000'000. Complete conversion is reached within 4 h with an enantioselectivity of 79% with an initial turnover frequency (tof) exceeding 1'800'000 h^-1. This sets a new standard for the technical application of enantioselective catalysts. Important aspects and results for the different phases of the process development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed.