Asymmetric Cascade Cyclization of Enynamides with Photogenerated Ketenes via Relay Gold and <i>N</i>-Oxide Catalysis

Abstract

An asymmetric cascade cyclization of enynamides and α-diazoketones to produce chiral bicyclic lactams bearing chiral all-carbon quaternary stereocenters is realized with up to 95% yield, 98% ee, and >19:1 dr. The combination of visible light photoactivation and the relay of gold and N-oxide catalysis in a cascade process enabled the facile generation and controlled assembly of two reactive intermediates, ketene and aza-o-quinone methide. Theoretical calculations revealed a stepwise [4 + 2] cycloaddition mechanism, with the stereochemistry controlled by the amide group of the catalyst. Remarkably, this study presents the first example of chiral N-oxides serving as catalysts for asymmetric ketene cycloaddition and illustrates how a cascade strategy could be a promising means to access significant chiral heterocyclic scaffolds.