Photocatalytic Activation of Fluoroform for Radical Trifluoromethylation.

Fluoroform is an ideal trifluoromethyl source in synthetic chemistry due to its low cost, low toxicity, and high potential for greenhouse-gas valorization. However, the use of fluoroform has been largely limited to the generation of trifluoromethyl anions or metal-bound species; direct access to the trifluoromethyl radical remains elusive, despite the broad applicability of radical trifluoromethylation for preparing medicinally important compounds. Here, we report a method for radical trifluoromethylation using fluoroform by leveraging the reactivity of ketones in combination with a Brønsted base under photoirradiation. The ketone-mediated photochemical activation provides access to the trifluoromethyl radical from fluoroform via a photoexcited alkoxide intermediate without exogenous redox reagents, enabling radical trifluoromethylation of alkenes and arenes under mild conditions. The developed system is amenable to a photocatalytic protocol, late-stage trifluoromethylation of complex molecules, and upgrading bulk chemicals into high-value trifluoromethylated compounds.