Substrate-controlled Rh(III)-catalyzed regiodivergent annulation towards fused and spiro benzimidazoles.

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.

Citation

Ying-Ti Huang, Indrajeet J Barve, Yi-Ting Huang, Sandip Dhole, Wei-Jung Chiu, Chung-Ming Sun. Substrate-controlled Rh(III)-catalyzed regiodivergent annulation towards fused and spiro benzimidazoles. Organic & biomolecular chemistry. 2022 Aug 31;20(34):6854-6862

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PMID: 35971982

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