Synthesis of chiral α-trifluoromethyl alcohols and ethers via enantioselective Hiyama cross-couplings of bisfunctionalized electrophiles

Abstract

Methods for synthesis of chiral organic compounds bearing trifluoromethyl-substituted stereocenters are of great interest for agrochemical and pharmaceutical labs and industries in their search for new bioactive materials. We report on employment of bisfunctionalized electrophiles, bearing both a trifluoromethyl and a functional group as direct substituents of the reactive center, in cross-coupling reactions. We exemplify this concept in the asymmetric synthesis of enantioenriched α-trifluoromethyl- and perfluoroalkyl-containing benzylic and allylic ethers and alcohols by nickel-catalyzed stereoconvergent Hiyama cross-coupling reaction. Substrate electrophiles are conveniently prepared in few steps from trifluoroacetic acid. The method represents a conceptually different approach to chiral CF3-substituted alcohols and ethers and allows for a rapid catalytic preparation of a wide range of these valuable compounds in high yields and enantioselectivity.