Synthesis of benzoazepine derivatives via Rh(iii)-catalyzed inert C(sp2)–H functionalization and [4 + 3] annulation

Abstract

In this paper, a novel and sustainable synthesis of the hitherto unreported 5H-benzo[c]imidazo[1,2-a]azepine-6-carboxylic acids via the cascade reactions of 2-arylimidazoles (1) with methylene-oxetanones (2) is presented. Mechanistically, the formation of the title compounds is triggered by a Rh(III)-catalyzed C(sp²)–H alkenylation of 1 with 2 followed by an intramolecular N-nucleophilic substitution. With this method, a series of hybrid compounds combining the biologically promising imidazole and benzoazepine moieties decorated with a synthetically versatile carboxyl group were prepared in moderate to good efficiency. In addition, the utility of the products thus obtained was remarkably showcased by their efficient transformations into some otherwise difficult-to-obtain pentacyclic compounds.