Pd‐Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF₂H Generated ex Situ

Abstract

Abstract An expedient ex‐situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd‐catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two‐chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two‐step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low‐cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine‐containing C 1 group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D 2 O to the DFIM‐generating chamber.