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.


Supplementary material

Supporting Information
Experimental procedures, additional reaction data, NMR spectra, computational data.