Visible light-driven modular synthesis of aza-β-lactams via a dual photochemical cascade

Abstract

The development of efficient and sustainable synthetic routes to nitrogen-containing heterocycles remains a cornerstone of modern organic chemistry. Herein, we report a visible-light-induced [2 + 2] cycloaddition reaction between photogenerated ketenes and azoarenes, providing a mild and high-yielding route to aza-β-lactams—versatile scaffolds with significant pharmaceutical and synthetic relevance. The ketene intermediates are generated in situ from N-tosylhydrazones under mild, transition metal-free conditions, leveraging visible light as a renewable energy source. This strategy delivers excellent yields (up to 99%) and exhibits broad substrate scope (22 examples), accommodating diverse electronic and steric variations. Notably, mechanistic insights, supported by experimental studies and density functional theory (DFT) calculations, reveal a stepwise pathway involving ketene formation followed by cyclization. This study expands the synthetic utility of photogenerated ketenes and further establishes a versatile platform for the controlled assembly of nitrogen-containing heterocycles under visible-light activation. The EcoScale evaluation of our optimized protocol yielded a score of 86.5, indicating an excellent level of sustainability based on reagent safety, energy input, and workup efficiency.