Photoredox-catalyzed cascade difluoromethylation/SO2 reintegration/polyfluoroarylation of conjugated dienes with a bifunctional CF2HSO2Na reagent

Abstract

Polyfluoroarylsulfones represent an important class of compounds with broad applications in pharmaceutical chemistry and materials science, yet their efficient and selective synthesis remains challenging. Herein, we report a visible-light-driven, photoredox-catalyzed cascade reaction that enables simultaneous difluoromethylation, sulfur dioxide reintegration, and polyfluoroarylation of conjugated dienes using sodium difluoromethanesulfinate (CF₂HSO₂Na) as a bifunctional reagent. This strategy leverages the dual role of CF₂HSO₂Na, which acts as both a source of CF₂H radicals and an in situ SO₂ surrogate, facilitating the atom-economical construction of polyfluoroaryl-substituted allylic sulfones under exceptionally mild conditions. The reaction proceeds with high regio- and stereoselectivity, affording either 1,4- or 1,2-addition products depending on the diene substrate. Notably, the method is applicable to commodity chemicals such as 1,3-butadiene and enables late-stage functionalization of complex polyfluoroarenes. Mechanistic studies and DFT calculations provide insight into the reaction pathway, including the unprecedented trapping of a delocalized allylic radical by SO₂ and the origin of selectivity. This work offers a practical, modular, and sustainable approach to accessing structurally diverse polyfluoroarylsulfones, with potential utility in synthetic and medicinal chemistry.