The chiral switch of metolachlor: The development of a large-scale enantioselective catalytic process

The development of an enantioselective catalytic process for the technical preparation of chiral agrochemicals is illustrated by the case history of t he herbicide (S)-metolachlor (trade name Dual Magnum(R)). Four synthetic ro utes were investigated in some detail. The key step for the technical proce ss of the enantiomerically enriched compound is the asymmetric hydrogenatio n of an imine intermediate made possible by a new iridium ferrocenyl diphos phine catalyst system. Using optimized conditions, the isolated imine can b e hydrogenated at a hydrogen pressure of 80 bar and 50 degrees C with a sub strate-to-catalyst ratio of >1'000'000. Complete conversion is reached with in 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 technica l 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.