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 NaSO2CF2H. This organocatalytic approach provides a practical route for the synthesis of pharmaceutically relevant alpha-aryl-beta-difluormethyl ketones without the need for transition metals or photocatalysts. The late-stage acyldifluoromethylation of drug analogues was also demonstrated. The reaction design employs NaSO2CF2H as the source of the CF2H radical in the presence of an oxidant for the radical relay.

Automated summary

An N-hetercyclic carbene-catalyzed three-component acyldifluoromethylation reaction has been developed, providing a practical route for the synthesis of pharmaceutically relevant compounds without the need for transition metals or photocatalysts. Late-stage acyldifluoromethylation of drug analogues was also successfully demonstrated in this study. The reaction utilizes NaSO2CF2H as the source of the CF2H radical with an oxidant for radical relay.