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Updated: Jul 11, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Electrophotochemical Synthesis Facilitated Trifluoromethylation of Arenes Using Trifluoroacetic Acid
Jing Qi1, Jinhui Xu1, Hwee Ting Ang1
1Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Abstract:
The trifluoromethyl (CF3) 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 CF3 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 CF3 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 CF3 radicals through oxidative decarboxylation. This strategy enables the sustainable and environmentally-friendly synthesis of CF3-, CF2H- 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 CF3 source.
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