Efficient Access to Multifunctional Trifluoromethyl Alcohols through Base-Free Catalytic Asymmetric C-C Bond Formation with Terminal Ynamides

摘要

The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF3-substituted tertiary propargylic alcohols in up to 99% yield and 96% ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the beta-hydroxy-beta-trifluoromethyl ynamides is exemplified by selective transformations to chiral Z- and E-enamides, an amide, and N, O-ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent beta-hydroxy ynamides.