Electrophotochemical Synthesis Facilitated Trifluoromethylation of Arenes Using Trifluoroacetic Acid.

The trifluoromethyl (CF 3 ) group is an essential moiety in medicinal chemistry due to its unique physicochemical properties. While trifluoroacetic acid (TFA) is an inexpensive and easily accessible reagent, its use as a source of CF 3 is highly challenging due to its high oxidation potential. In this study, we present a novel electrophotochemical approach that enables the use of TFA as the CF 3 source for the selective, catalyst- and oxidant-free trifluoromethylation of (hetero)arenes. Key to our approach is the selective oxidation of TFA over arenes, generating CF 3 radicals through oxidative decarboxylation. This strategy enables the sustainable and environmentally-friendly synthesis of CF 3 -, CF 2 H- and perfluoroalkyl-containing (hetero)arenes with a broad range of substrates. Importantly, our results demonstrate significantly improved chemoselectivity by light irradiation, opening up new possibilities for the synthetic and medicinal applications of TFA as an ideal yet underutilized CF 3 source.