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. 2021 Oct;13(10):1006-1016.
doi: 10.1038/s41557-021-00746-7. Epub 2021 Jul 19.

A ring expansion strategy towards diverse azaheterocycles

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A ring expansion strategy towards diverse azaheterocycles

Ruirui Li et al. Nat Chem. 2021 Oct.

Abstract

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 π bonds. However, in some cases such strategies suffer from some limitations owing to the difficulties in controlling the regioselectivity and the accessibility of specific π-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 Pd0 species during the reaction.

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