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

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