Enantioselective Catalysis for Agrochemicals: The Case History of the DUAL MAGNUM® Herbicide

The use of enantioselective catalytic methods for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-merolachlor (trade name DUAL MAGNUM®). The key step for the technical synthesis of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate, made possible by a new iridium-ferrocenyldiphosphine catalyst system. Important aspects of the development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed

Biotin – The Chiral Challenge

In this contribution, the first examples of the catalytic highly enantioselective reduction of cyclic meso-anhydrides to lactones and of thioanhydrides to thiolactones are described. The N-benzyl protected key building blocks in the industrial synthesis of (+)-biotin were so far only accessible by usage of expensive reagents in multi-step procedures. In contrast, homogeneous catalytic enantioselective hydrogenation of the corresponding meso-anhydride mediated by a metal phosphane complex proceeds with high optical induction (ee >95%) and excellent yield. The catalytic system provides a generally applicable new method for the preparation of lactones from cyclic anhydrides

Strategies for Accelerating the Development of Catalytic Enantioselective Reactions

The development of enantioselective catalytic processes for the manufacture of chiral intermediates is a very complex endeavor and can be very time consuming and expensive. In this contribution the major issues which might lead to long development times will be discussed and strategies to deal with these problems are described. The general part is illustrated with the approach Solvias has chosen for assisting and supporting the development of enantioselective homogeneous hydrogenation processes, at the moment the most important industrial application of asymmetric catalysis. Special emphasis is given to the application of high-throughput screening (HTS) using a Symyx HiP system and the description of the Solvias portfolio of chiral ligands which makes a broad variety of diphosphine ligands available for all phases of process development from the first screening experiments to the large-scale manufacturing phase. Four case histories serve to illustrate the generic description of the development process

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 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

Exploring Stereogenic Phosphorus: The Search for New Chiral Diphosphines

The synthesis of P-stereogenic ligands bearing 2,6-disubstituted phenyl groups at the P atom is a challenging problem. The results reported herein help define the scope and limitations of the existing synthetic protocols, such as Jugé's oxazaphospholidine borane method and the enantioselective deprotonation of P(BH3)(CH3)2(R) developed by Evans and Imamoto. Jugé's new approach based on chlorophosphine boranes was exploited for the preparation of a C1-symmetric MiniPhos-like ligand. Preliminary results concerning the application of the new ligands in the rhodium and ruthenium hydrogenation of olefins are also reported