Biocatalytic asymmetric reduction of fluoroalkyl ketones to access enantiopure fluoroalkyl secondary alcohols.

Abstract

An efficient biocatalytic reduction of difluoroalkyl ketones for accessing chiral fluoroalkyl secondary alcohols is reported using commercial NADPH-dependent ketoreductase K234 with 2-propanol as a co-substrate for NADPH regeneration. This bioreduction reaction could be applied to a broad range of prochiral fluoroketones including aryl difluoroketones, aliphatic difluoroketones, and trifluoroacetophenones with excellent conversion and favorable enantioselectivity at high substrate concentrations (100 g L-1). These results indicate the potential of K234 for the industrial production of valuable chiral fluorohydrins. Moreover, this biocatalytic protocol could also be effective without the addition of an external nicotinamide cofactor, which provides useful guidance for further application of ketoreductase K234 in the asymmetric synthesis of chiral secondary alcohols.