Rapid Synthesis of Benzimidazole-Fused Isoindoles by Rh(III)/Ru(II)-Catalyzed [4 + 1] Cascade C-H/N-H Annulation of 2-Arylbenzimidazoles with Alkynoates and Alkynamide

Ying-Ti Huang; Indrajeet J Barve; Ganesh P Pawar; Chung-Ming Sun

doi:10.1021/acs.joc.3c00937

Rapid Synthesis of Benzimidazole-Fused Isoindoles by Rh(III)/Ru(II)-Catalyzed [4 + 1] Cascade C-H/N-H Annulation of 2-Arylbenzimidazoles with Alkynoates and Alkynamide

J Org Chem. 2023 Aug 4;88(15):10916-10924. doi: 10.1021/acs.joc.3c00937. Epub 2023 Jul 14.

Authors

Ying-Ti Huang¹, Indrajeet J Barve^{1

2}, Ganesh P Pawar¹, Chung-Ming Sun^{1

3}

Affiliations

¹ Department of Applied Chemistry, National Chiao-Tung University, 1001 Ta-Hsueh Road, Hsinchu 300-10, Taiwan.
² Department of Chemistry, MES Abasaheb Garware College, Pune 411004, Maharashtra, India.
³ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 807-08, Taiwan.

PMID: 37450843
DOI: 10.1021/acs.joc.3c00937

Abstract

A Rh(III)-catalyzed [4 + 1] cyclization of 2-arylbenzimidazoles with alkynoates through C-H activation/ortho-alkenylation/intramolecular annulation cascade to obtain benzimidazole-fused isoindoles is reported. The reaction of the Rh catalyst and internal alkyne ester provides benzo[4,5]imidazo[2,1-a]isoindole acetate exclusively. Conversely, internal alkyne amide participates in the annulation process in the presence of a Ru catalyst to provide benzo[4,5]imidazo[2,1-a]isoindole acetamide. The alkyne acts as a C1 synthon and undergoes [4 + 1] cyclization rather than traditional [4 + 2] annulation.