Synthesis of Chiral Nonracemic alpha-Difluoromethylthio Compounds with Tetrasubstituted Stereogenic Centers via a Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

摘要

The synthesis of chiral, nonracemic difluoromethylthio (SCF2H) compounds that contain a tetrasubstituted stereogenic center is reported. Racemic alpha-SCF2H-beta-ketoallylesters 5 were initially prepared by an electrophilic difluoromethylthiolation of beta-ketoallylesters 6, followed by a Pd-catalyzed Tsuji decarboxylative asymmetric allylic alkylation (DAAA) to provide a wide variety of chiral, nonracemic alpha-allyl-alpha-SCF2H-ketones (4) with high enantiopurity. This strategy can be extended to the enantioselective synthesis of chiral, nonracemic alpha-allyl-alpha-trifluoromethylthio(SCF3)-ketones (7).