Electrochemical trifluoromethylation of imidazoles: Mechanistic insight from computation

Despite their wide application in everyday laboratory work and industry, mechanistic investigations of electrochemical, photo redox, and photoelectrochemical reactions using quantum chemistry are relatively rare. This can be attributed to two main factors: (a) complexity of the underlying reactivity, which is still poorly understood, and (b) methodological difficulties in interpreting quantum chemical calculations in the context of reactions that involve both acid/base-chemical steps and electron transfers. While (a) is an inherent problem, concerning (b), redox–acid/base phase diagrams provide a theoretical framework that allows a systematic investigation of redox-chemical reaction mechanisms. In the present work, the electrochemical trifluoromethylation of Methyl 1-methyl-1 H -imidazole-4-carboxylate with Langlois reagent (Na[CF 3 SO 2 ]) is investigated with density functional theory calculations using redox–acid/base phase diagrams. Generally, our results are in good agreement with experimental findings. Furthermore, our results predict a tunable selectivity depending on the electro- and acid/base-chemical conditions. • Reaction mechanism of electrochemical trifluoromethylation elucidated computationally. • DFT predicts a tunable regio-selectivity depending reaction conditions. • First application of redox–acid/base phase diagrams to a complete reaction mechanism. • Excellent agreement with experimentally observed regio-selectivity.