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

Org Lett. 2022 Jul 8;24(26):4840-4844. doi: 10.1021/acs.orglett.2c02093. Epub 2022 Jun 27.

Abstract

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 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 NaSO2CF2H as the source of the CF2H radical in the presence of an oxidant for the radical relay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes*
  • Catalysis
  • Ketones*
  • Methane / analogs & derivatives
  • Molecular Structure

Substances

  • Aldehydes
  • Ketones
  • carbene
  • Methane