Alkyl-substituted 2-arylbenzimidazole, a privileged structure in drug discovery, has been identified in numerous significant pharmaceutical or bioactive compounds. Conventionally, the synthesis of 2-arylbenzimidazole with substituted diversity often suffer from the requirement of pre-functionalized starting materials (such as aldehydes and o-diaminobenzenes) and lengthy synthetic steps as well as harsh reaction conditions, particularly when alkyl-substituted aryl partners are involved. Given the rapid progress in transition metal-catalyzed C—H activation, the direct C—H alkylation of imidazoles represents a more rational and highly desirable approach due to their ready availability and inherent directing ability for transition metal catalysts. A rhodium(III)-catalyzed C—H allylation of 2-arylbenezimidazole with readily available 4-vinyl-1,3-dioxolan-2-one, based on our group's recent research progress in the C—H functionalization of 2-arylimidazoles, is described. The protocol described herein exhibits mild reaction conditions, scalability, and broad functional group tolerance, enabling efficient coupling of structurally diverse substrates without the need for protecting groups. General procedure for the C—H allylation reaction of 2-arylbenzimidazoles with 4-vinyl-1,3-dioxolan-2-one is as follows: Under a nitrogen atmosphere, a dry Schlenk tube was charged with 2-arylbenzimidazole (1a~1r) (0.2 mmol, 1.0 equiv.), [RhCp*Cl₂]₂ (6.2 mg, 0.01 mmol, 5 mol%), KOAc (5.9 mg, 0.06 mmol, 30 mol%), 4-vinyl-1,3-dioxolan-2-one (2a) (34.2 mg, 0.3 mmol, 1.5 equiv.), and hexafluoroisopropanol (HFIP, 1.5 mL) as the solvent. The reaction mixture was stirred at 80 ℃ for 18 h. Upon completion of the reaction [monitored by thin-layer chromatography (TLC)], the reaction mixture was diluted with ethyl acetate (EtOAc) (5 mL). The solvent was removed in vacuo to afford the crude product. Purification of the crude product via flash column chromatography [silica gel, V(n-hexanes)∶V(EtOAc)=2∶1] afforded the corresponding white solids 3a~3r as the target compounds. Based on the significance of the 2-arylbenzimidazole scaffold in medicinal chemistry, this efficient transformation strategy is expected to provide a novel approach for preparing alkylated 2-arylbenzimidazole derivatives with biological activity and synthetic potential.

Key words: Rh(III)-catalyzed reaction, C—H activation, 2-arylbenzimidazole, 4-vinyl-1,3-dioxolan-2-one, C—H allylation