Highly Enantioselective Decarboxylative Difluoromethylation
Xian Zhao, Chao Wang, Lingfeng Yin, Wei Liu
Abstract
Organofluorine molecules that contain difluoromethyl groups (CF 2 H) at stereogenic centers have gained importance in pharmaceuticals due to the unique ability of CF 2 H groups to act as lipophilic hydrogen bond donors. Despite their potential, the enantioselective installation of CF 2 H 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.