Electrooxidative Pd-Catalyzed Remote Hydrofunctionalization of Alkenes with Nucleophiles

The catalytic hydrofunctionalization of alkenes with nucleophiles via the generation of carbocationic intermediates has been extensively studied as an efficient strategy for the regioselective installation of functional groups on alkene feedstocks. However, since the established methods are confined to functionalization of the position where the alkene is originally located, it is highly desirable to develop a broadly applicable catalytic hydrofunctionalization platform that offers an alternative regioselectivity that is otherwise challenging to achieve with existing protocols. Herein, we report a remote alkene hydrofunctionalization method enabled by electrooxidative palladium hydride catalysis. The key to success is the formation of a remote carbocation intermediate through a mechanistic pathway, which involves a chain-walking process followed by anodic oxidation of an organopalladium species. This method allows remote hydrofunctionalization of terminal and internal alkenes with a broad range of oxygen, carbon, nitrogen, and fluoride nucleophiles, including complex drug-like molecules.