Atomically Dispersed Fe–N–C-Catalyzed Intermolecular Reductive Coupling toward the Synthesis of Benzimidazoles
Zhuang Ma, Binyu Zhang, Zhuo He, Ting Xu, Yuhe Cheng, Y. D. Cui, Zupeng Chen
Abstract
Benzimidazoles are privileged structural motifs in pharmaceuticals due to their diverse biological activities. Herein, we report an atomically dispersed iron catalyst (Fe-NC-800) for the reductive coupling of 2-nitroacetanilides with various aldehydes to synthesize structurally diverse benzimidazoles. The catalyst is synthesized through a template-sacrificial strategy and contains atomically dispersed Fe–N 4 active sites embedded in a nitrogen-doped carbon matrix. This transformation proceeds with high efficiency (conversion: 100%; yield: up to 89%), broad substrate scope (>50 samples), and functional group tolerance, delivering valuable benzimidazoles with good yields. Notably, this method achieves benzimidazole synthesis via an intermolecular coupling rather than an intramolecular cyclization process, distinguishing it from conventional strategies. Mechanistic studies reveal a stepwise hydrogenation pathway involving imine and amine intermediates, with Fe–N sites playing a crucial catalytic role. Additionally, the catalyst demonstrates great recyclability and stability, making it a promising platform for modern organic synthesis.