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Electrochemically-Driven 1,4-Aryl Migration via Radical Fluoromethylation of N-Allylbenzamides: a Straightforward
Etienne Derat1, Géraldine Masson2,3, Aurélie Claraz2
1Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, 4 Place Jussieu, CC 229, 75252, Paris Cedex 05, France.
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 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.
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