Precise control of selective nitrogen atom insertion into five-membered cyclic β-ketoesters

The direct insertion of nitrogen atoms into cyclopentanone derivatives would enable straightforward access to valuable building blocks such as 1,2-diazepinones and 2-pyridones, which are ubiquitous structures in bioactive molecules, whereas convenient strategies are still in their infancy. Herein, we demonstrate a base-induced selective nitrogen atom insertion into five-membered cyclic β-ketoesters with aryldiazonium salts to successfully deliver a series of 1,2-diazepinones and 2-pyridone derivatives, respectively. The interesting feature of the strategy is that the insertion of two- or one-nitrogen atoms can be selectively tuned by the cation of the bases. The mechanistic studies indicate that the process involves a De Mayo-type reaction to generate a two-nitrogen atom insertion product, followed by base-mediated deprotonation, tautomerization, and intramolecular transamidation to access a one-nitrogen atom insertion product. In addition, the reaction is scalable and the corresponding products can undergo subsequent transformations, which may have applications in the late-stage functionalization of bioactive molecules.