Construction of C-X (X = S, O, Se) Bonds via Lewis Acid-Promoted Functionalization of Trifluoromethylarenes

The conversion of easily available trifluoromethylarenesthroughC-F bond activation provides an attractive pathway for rapidaccess to difluorobenzylic substructures in producing pharmaceuticalsand agrochemicals. However, recent advances in this area have beenconfined to C-C-(H) bond construction, thus limiting the diversityof the accessible motifs. In contrast, the selective formation ofa carbon-heteroatom bond via C-F bondfunctionalization, which enable fast and convenient access to diversefluorine-containing motifs with high chemical diversity, remains aformidable synthetic challenge. Herein, we disclosed a Lewis acidpromoted photoredox-catalyzed strategy for the construction of C-X(X = S, O or Se) bonds by single C-(sp(3))-F bond activationof trifluoromethylarenes, which enable the direct synthesis of medicinallyinteresting aryldifluoromethyl ether [ArCF2X- (X= S, O, or Se)] scaffolds. This method relies on readily availablereagents and can tolerate a range of thiol, phenol, and selenol nucleophiles.Its utility was exemplified in the late-stage modifications of severalpharmaceutical ingredients. Preliminary studies suggest two parallelpathways: a photocatalytic single electron-transfer (SET), and anelectron donor-acceptor (EDA) process.