Photoelectrochemical Remote α- and β-C(sp3)-H Alkenylation of Amines

A general method for photoelectrochemical site‐selective α- and β-C(sp3)−H alkenylation of amines with vinyl bromides has been developed. Regioselective activation of inert C−H bonds is achieved by intramolecular hydrogen atom abstraction (HAT) by an oxidatively generated aryl radical. Depending on the HAT directing group attached to the amines’ N-atom, either 1,5- or 1,6-H-atom transposition occurred, leading to regioisomeric carbon-centered radical species. C‐radicals thus formed at the α/β‐position of the amines' functionality undergo radical cross-coupling with Ni complex-activated vinyl bromide to provide the corresponding α- or β‐functionalized amines. Good functional group tolerance, the gram-scale experiments, post-functionalization and demonstration of preparation of key structural scaffolds of the selected naturally occurring compounds and drug candidates greatly highlight the potential applicability of the presented method. The mechanistic experiments demonstrated that the reported protocol consists of a photoelectrochemically induced thiyl radical cycle and an electrochemically driven Ni-catalytic cycle. The first one is responsible for the generation of CO2˙ˉ, a XAT reagent capable of activation of aryl halide to provide aryl radical species. Cathodic reduction of a Ni(I) intermediate to the Ni(0) complex allows closing the Ni-catalyzed cycle, enabling the execution of the cross-coupling stage leading to a C-H functionalized amine derivative.