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

ABSTRACT

An 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 ß-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.