Base-Dependent Divergent Carbodifluoroalkylation and Halodifluoroalkylation of Alkenes under Visible-Light Irradiation.

Abstract

Organic molecules containing a difluoroalkyl group are valuable and versatile chemicals because of their unique physicochemical and biological properties. Accordingly, the development of efficient and practical difluoroalkylation for the preparation of these compounds is important and attractive. Herein, we demonstrate photoredox-catalyzed and base-dependent selective carbodifluoroalkylation and halodifluoroalkylation of alkenes using readily available 2-(allyloxy)arylaldehydes [or 2-(allylamino)arylaldehydes] and XCF₂COOEt (or BrCF₂CONR¹R²) as starting materials. The developed reaction enables convenient and accurate synthesis of difluoroalkylated chroman-4-ones and aldehydes and features broad substrate scope, mild conditions, and operational simplicity. Moreover, gram-scale product preparation and application of the title protocol in late-stage functionalization of pharmaceutical molecules are accomplished.