Metal- and photosensitizer-free hydrodifluoromethylation of unactivated alkenes via acetamide-activated difluoromethyl aryl sulfones

Abstract

Herein, we report a photocatalyst- and metal-free, visible-light-induced hydrodifluoromethylation of unactivated alkenes via an acetamide-mediated activation of difluoromethyl aryl sulfones, a class of bench-stable CF₂H reagents. The cooperative roles of acetamide, KF, and H₂O enable efficient CF₂H radical generation under blue-light irradiation in DMSO, affording hydrodifluoromethylated products in good yields with broad substrate scope and functional group tolerance. This protocol features tunable regioselectivity, furnishing both anti-Markovnikov and Markovnikov hydrodifluoromethylated products. Mechanistic investigations reveal the formation of an electron donor–acceptor (EDA) complex between acetamide and the difluoromethyl aryl sulfone, which, upon visible-light excitation, undergoes single-electron transfer (SET) followed by C–S bond fragmentation to generate CF₂H radicals under mild conditions. This work establishes a practical and sustainable strategy for direct CF₂H incorporation into complex molecular scaffolds and expands the synthetic potential of Hu reagents in fluorine chemistry and the modification of alkene-containing natural products and complex bioactive molecules.