Substrate-controlled Rh(iii)-catalyzed regiodivergent annulation towards fused and spiro benzimidazoles?

Organic & Biomolecular Chemistry Pub Date: 2022-08-03 DOI: 10.1039/D2OB00906D

Abstract

A Rh(III)-catalyzed cascade C–H activation and cyclization of 2-aryl benzimidazoles with maleimides for the synthesis of benzimidazole-fused isoquinolines and benzimidazole-spiro isoindoles is reported. Switchable selectivity towards the formation of these two distinct products can be achieved using unsubstituted and substituted benzimidazoles at the ortho-position of the phenyl ring. Mechanistically, C–H activation followed by migratory insertion of maleimide forms a Heck-type intermediate. Unsubstituted benzimidazole undergoes aza-Michael addition to form a (4 + 2) fused product, whereas ortho-substituted phenyl benzimidazole causes steric clash to deliver a (4 + 1) spiro-adduct favorably via acid-catalyzed intramolecular annulation.

Graphical abstract: Substrate-controlled Rh(iii)-catalyzed regiodivergent annulation towards fused and spiro benzimidazoles
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