Chiral Arylthiol-Catalyzed Asymmetric Hydrodifluoroalkylation of Alkenes Facilitated by Noncovalent Interaction.

Abstract

Chiral gem-difluorinated indane scaffolds are valuable fluorinated bioisosteres of medicinally important CH2-containing indane frameworks. Herein, a photodriven enantioselective hydrodifluoroalkylation of methyleneindanes with α-bromodifluoroamides catalyzed by a C2-symmetric chiral arylthiol was developed. This protocol delivers chiral gem-difluorinated indane-derived amides in good to excellent yields with high enantioselectivities. Mechanistic investigation reveals that the gem-dimethyl substituent in the substrate is critical to amplify the free energy difference between diastereomeric HA transition states, while a π-π interaction between the substrate N-phenyl group and the arylthiol catalyst benzylic substituent underpins the enantiocontrol.