Synthesis of 2,3-Dihydro‑1H‑azepine and 1H‑Azepin-2(3H)‑one Derivatives From Intramolecular Condensation between Stable Tertiary Enamides and Aldehydes

A new strategy to construct 2,3-dihydro-1H-azepine and 1H-azepin-2­(3H)-one heterocyclic rings is reported based on emerging tertiary enamide synthons. Under very mild conditions employing BBr3 as a Lewis acid catalyst and P2O5 as an additive, tertiary enamides that contain a formyl group underwent highly efficient and scalable intramolecular cyclic condensation to afford diverse 2,3-dihydro-1H-azepine and 1H-azepin-2­(3H)-one derivatives in 71–96% yields. The reaction proceeded most probably through a nucleophilic addition of enamides to aldehyde, deprotonation, and dehydration cascade. Application of the method in the synthesis of dihydro-azepino­[2,1-a]­isoindol-5-ones, the core structure of naturally occurring lennoxamine, was also demonstrated.