A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study

A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfmate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.