HFIP‐Assisted Single C−F Bond Activation of Trifluoromethyl Ketones using Visible‐Light Photoredox Catalysis

• Published in: Angewandte Chemie International Edition 2022-02, Vol.61 (9), p.e202115272-n/a
• Main Authors: Ghosh, Soumen, Qu, Zheng‐Wang, Pradhan, Suman, Ghosh, Avisek, Grimme, Stefan, Chatterjee, Indranil
• Format: Article
• Language: English
• Subjects: Catalysis; Cleavage; C−F bond activation; density functional calculations; Fluorine; Functional groups; HFIP; Ketones; Photoredox catalysis; Single electrons; α,α-difluoroketones
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202115272

A visible light photoredox catalytic method for the selective cleavage of single strong C−F bond in trifluoromethyl ketones is reported. Single electron reduction of trifluoromethyl ketones generates difluoromethyl radicals which can be engaged in intermolecular C−C bond formation with N‐methyl‐N‐arylmethacrylamides to furnish fluorine‐containing oxindole derivatives in good yields. The reaction shows excellent chemoselectivity with good functional group tolerance under mild conditions. 1,1,1,3,3,3‐Hexafluoroisopropanol (HFIP) as a solvent plays a critical role for the selective single C−F bond cleavage. High‐level DFT calculations are depicted to shed light on the mechanism. Single and selective C−F bond activation of trifluoromethyl ketones via visible‐light photoredox catalysis is achieved in the presence of HFIP solvent. Trapping of photo‐catalytically generated difluoromethyl radical to acrylamide derivatives furnishes an essential class of difluoromethyl‐containing oxindole scaffolds. A high level of DFT calculations strongly supports our proposed mechanistic pathway for this novel transformation.