Nickel-Catalyzed Cross-Coupling of Arylboronic Acids with Ethyl 3-Bromo-2,2-difluoropropanoate

The difluoromethylene group is a key fluorinated moiety in drug design, capable of providing desirable physicochemical properties and bioactivity. Despite this importance, very few methods have been reported for the one-step synthesis of β-difluoroaryl propionate derivatives, which are valuable potential drug intermediates. Therefore, this study developed a nickel-catalyzed cross-coupling reaction that employs ethyl 3-bromo-2,2-difluoropropanoate as a novel fluoroalkylating agent with arylboronic acids. The developed method enabled the efficient construction of β-difluoroaryl propionates under mild conditions, and showcased broad substrate scope coupled with exceptional functional group tolerance. Thus, this work offers a simple and efficient synthetic route to access these valuable fluorine-containing frameworks.