Organocatalytic Three-Component Acyldifluoromethylation of Vinylarenes via N -Heterocyclic Carbene-Catalyzed Radical Relay.

We herein describe an N -hetercyclic carbene-catalyzed three-component acyldifluoromethylation of vinylarenes, aldehydes, and NaSO 2 CF 2 H. This organocatalytic approach provides a practical route for the synthesis of pharmaceutically relevant α-aryl-β-difluormethyl ketones without the need for transition metals or photocatalysts. The late-stage acyldifluoromethylation of drug analogues was also demonstrated. The reaction design employs NaSO 2 CF 2 H as the source of the CF 2 H radical in the presence of an oxidant for the radical relay.