Base-mediated synthesis of benzimidazole-fused 1,4-benzoxazepines via sequential intermolecular epoxide ring-opening/intramolecular SNAr reactions

Abstract

We have developed a transition-metal-free, practical route to benzimidazole-fused 1,4-benzoxazepines. Operationally, the protocol involves a K2CO3-mediated intermolecular ring opening of terminal epoxides by 2-(2-fluorophenyl)benzimidazole, followed by an intramolecular nucleophilic aromatic substitution (SNAr) reaction of the resulting products in the presence of NaH. We have also achieved an 11-step synthesis of a chroman-linked benzimidazole-fused 1,4-benzoxazepine using a phenoxide-ion induced 6-exo intramolecular epoxide ring-opening and an alkoxide-ion induced intramolecular SNAr reaction as key steps.