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

作者：Liu, Dan; Shu, Zhen-Cao; Zhang, Zhihan; Wang, Ze-Tian; Wang, Liang; Xie, Ming-Sheng^*; Guo, Hai-Ming; Lu, Liang-Qiu^*; Xiao, Wen-Jing^*

来源：ACS Catalysis, 2024, 14(3): 1741-1749.

DOI：10.1021/acscatal.3c05731

• asymmetric cyclization
• cascade reaction
• goldcatalysis
• ketene
• organocatalysis
• visiblelight

An asymmetric cascade cyclization of enynamides and alpha-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.