Formal [1,5] Rearrangement of Cyclopropanone Hemiaminals: Synthesis of Tetrahydrobenzazepinone Derivatives

A convergent synthetic approach to the formation of tetrahydrobenzazepin-2-ones from 2-aminobenzaldehyde derivatives and cyclopropanone surrogates is reported. In this process, a stable hemiaminal intermediate spontaneously rearranges at room temperature upon generation of a remote iminium species, via a concerted and diastereoselective ring opening/homo-Mannich pathway occurring through a boat transition state. Such a formal [1,5] rearrangement of cyclopropanone hemiaminals is unprecedented and thus represents a novel strategy for the elaboration of seven-membered heterocyclic compounds.