Organocatalytic Three-Component Acyldifluoromethylation of Vinylarenes via <i>N</i>-Heterocyclic Carbene-Catalyzed Radical Relay
Kun She, Liang Feng, Shichao Tian, Heng‐Shan Wang, Gavin Chit Tsui, Quande Wang
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.
Topics & Concepts
ChemistryCarbeneCatalysisArylCombinatorial chemistryRadicalRelayComponent (thermodynamics)OrganocatalysisOrganic chemistryEnantioselective synthesisPower (physics)AlkylThermodynamicsQuantum mechanicsPhysicsFluorine in Organic ChemistryRadical Photochemical Reactions