Copper-Mediated Oxidative Chloro- and Bromodifluoromethylation of Phenols

J Am Chem Soc. 2023 Nov 8;145(44):23899-23904. doi: 10.1021/jacs.3c08858. Epub 2023 Oct 25.

Abstract

The first oxidative chloro- and bromodifluoromethylation of phenols with (CH3)3SiCF2X and CuX (X = Cl or Br) in the presence of Selectfluor under mild reaction conditions was developed. This protocol provided a practical and efficient method for the synthesis of a diverse range of biologically valuable and synthetically challenging chloro- and bromodifluoromethyl aryl ethers. Preliminary mechanistic studies suggest that this reaction proceeded through a difluorocarbene-involved oxidative coupling process.