Industrial-Scale Enantioselective Hydrogenation using Pfaltz-Type Catalysts: Chemical Development and Academic Collaborations

The use of modern catalytic methods, such as enantioselective hydrogenation in multi-hundred metric ton scale, still offers many challenges and is accordingly relatively rare. A robust and economical process demands identification of the right catalytic system and conditions that allow for full conversion and high stereo- and chemoselectivity at very low catalyst loadings.

Crabtree/Pfaltz-Type iridium complexes are one of the very few options to achieve high enantioselectivity in the hydrogenation of non-functionalized olefins. However, the high price of iridium demands substrate to catalyst ratios in the order of 10000:1 for attractive use cases in CropScience, which has been out of reach so far.

In search of a new production process for the novel fungicide Inpyrfluxam, we identified a single promising Crabtree/Pfaltz-Type Iridium complex using plate screening technology. Though only 25 turnovers were achieved initially, our labs succeeded in increasing this number to >10000 turnovers in collaboration with partners in both industry and academia. Moreover, we achieved not only excellent enantioselectivities of >97% ee, but also very attractive space-time yields.

Research activities included optimization of the catalyst structure, reaction solvent, and additives, as well  the large-scale procedure for preparing the chiral ligand backbone of catalyst SSCH1049.