Highly Enantioselective Decarboxylative Difluoromethylation.

Organofluorine molecules that contain difluoromethyl groups (CFH) at stereogenic centers have gained importance in pharmaceuticals due to the unique ability of CFH groups to act as lipophilic hydrogen bond donors. Despite their potential, the enantioselective installation of CFH groups into readily available starting materials remains a challenging and underdeveloped area. In this study, we report a nickel-catalyzed decarboxylative difluoromethylation reaction that converts alkyl carboxylic acids into difluoromethylated products with exceptional enantioselectivity. This Ni-catalyzed protocol exhibits broad functional group tolerance and is applicable for synthesizing fluorinated bioisosteres of biologically relevant molecules.