Ene-gamma-lactam synthesis via (3+2) vinyl azide-enolate cycloaddition: Enolate addition to vinyl triazolinone intermediates

Vinyl azides have undergone a recent renaissance as versatile synthetic reagents, however their reactivity as 1,3-dipoles in (3+2) cycloadditions remains underexplored. Here the synthesis of ene-gamma-lactam scaffolds via (3+2) cycloaddition of alpha-substituted vinyl azides with ester enolates is established. Mechanistic investigations, including isolation of reaction intermediates and density functional theory calculations, implicate an unprecedented conjugate-type addition to the exocyclic alkene of an N-vinyl triazolinone intermediate generated in the cycloaddition step. Determination of the reaction scope and application to synthesis of the natural product sargassumlactam is reported.