Electrochemically‐Driven 1,4‐Aryl Migration via Radical Fluoromethylation of N‐Allylbenzamides: a Straightforward Access to Functionalized β‐Arylethylamines

Abstract

AbstractAn electrochemical radical Truce Smiles rearrangement of N‐allylbenzamides is documented herein. The selective 1,4‐aryl migration was triggered by the radical fluoromethylation of the alkene providing a direct route to fluoro derivatives of the highly privileged β‐arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current to drive the oxidative process under mild reaction conditions. It accommodates a variety of migratory aryl groups with different electronic properties and substitution patterns. Careful selection of the protecting group on the nitrogen atom of the N‐allylbenzamide is crucial to outcompete the undesired 6‐endo cyclization and achieve high level of selectivity towards the 1,4‐aryl migration. DFT calculations support the reaction mechanism and unveil the origin of selectivity between the two competitive pathways.