A ring expansion strategy towards diverse azaheterocycles

The development of innovative strategies for the synthesis of N-heterocyclic compounds is an important topic in organic synthesis. Ring expansion methods to form large N-heterocycles often involve the cycloaddition of strained aza rings with pi bonds. However, in some cases such strategies suffer from some limitations owing to the difficulties in controlling the regioselectivity and the accessibility of specific pi-bond synthons. Here, we report the development of a general ring expansion strategy that involves a formal cross-dimerization between three-membered aza heterocycles and three- and four-membered-ring ketones through synergistic bimetallic catalysis. These formal cross-dimerizations of two different strained rings are efficient and scalable, and provide a straightforward and broadly applicable means of assembling diverse N-heterocycles, such as 3-benzazepinones, dihydropyridinones and uracils, which are versatile units in numerous drugs and biologically active compounds. Preliminary mechanistic studies revealed that the C-C bond of strained ring ketones is first cleaved by the Pd-0 species during the reaction.

Automated summary

This study presents a novel ring expansion strategy involving the cross-dimerization of different strained rings through synergistic bimetallic catalysis, providing an efficient and scalable method for assembling diverse N-heterocycles. Preliminary mechanistic studies reveal that the C-C bond of strained ring ketones is cleaved by the Pd-0 species during the reaction.