Visible-light-mediated substituent-controlled regiodivergent (2 + 2)/(3 + 2) cycloadditions for the synthesis of aza-analogs of β-lactam and γ-fused lactam derivatives

Abstract

While photocatalysis has garnered considerable attention within the field of organic chemistry, there remains a pressing need for innovative advancements to facilitate efficient and versatile synthesis processes. In this context, we present a novel approach for the construction of lactam derivatives, leveraging the in situ formation of ketenes via the visible-light-induced Wolff rearrangement of α-diazoketones and azo esters. The intrinsic electronic characteristics of the substituents on the azo esters are pivotal in dictating the chemoselectivity of the reaction, thus enabling a controlled and diverse synthesis of aza-analogues of β-lactams and γ-fused lactams. This method stands out for its simplicity, as it eschews the need for any external catalysts or additives, thereby mitigating potential environmental and economic impacts. Moreover, the synthesized products exhibit a high degree of versatility, as evidenced by a range of subsequent transformation reactions, showcasing the potential for further functionalization and application.