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Pd‐Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF 2 H Generated ex Situ
Author(s) -
Gedde Oliver R.,
Bonde Andreas,
Golbækdal Peter I.,
Skrydstrup Troels
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202200997
Subject(s) - aryl , catalysis , chemistry , halide , boronic acid , iodide , sulfolane , combinatorial chemistry , sodium iodide , organic chemistry , solvent , alkyl
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.