Solvent-Controlled Divergent Synthesis of (Seleno)urea-Containing Benzimidazoles from 1,2-Diisocyanobenzenes and Secondary Amines

Abstract

A solvent-controlled cascade cyclization of readily accessible 1,2-diisocyanobenzenes, selenium powder, and secondary amines has been developed for the divergent synthesis of previously inaccessible (seleno)urea-containing benzimidazoles. The transformation proceeds under mild, transition-metal-free conditions and exhibits pronounced solvent-dependent chemoselectivity, affording selenourea-functionalized benzimidazoles in water and urea analogues in DMSO. The protocol features broad substrate scope, excellent functional group tolerance, and compatibility with both aromatic and aliphatic secondary amines, enabling late-stage functionalization of bioactive molecules. Mechanistic investigations suggest initial formation of selenourea-containing benzimidazoles via cascade cyclization, followed by DMSO/O2-mediated oxidative deselenization in the presence of base to furnish the urea products. This work provides a concise and versatile strategy for the divergent construction of benzimidazole-based heterocyclic hybrids.