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Pd‐Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF(2)H Generated ex Situ

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 effe...

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Detalles Bibliográficos
Autores principales: Gedde, Oliver R., Bonde, Andreas, Golbækdal, Peter I., Skrydstrup, Troels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321866/
https://www.ncbi.nlm.nih.gov/pubmed/35388933
http://dx.doi.org/10.1002/chem.202200997
Descripción
Sumario: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.