TBTH (Bu3SnH) catalyzed C-H and C-Cl functionalization: Radical cascade cyclization for the construction of tetracyclic benzimidazole derivatives

Abstract

A radical cascade cyclization of cyanamides, catalyzed by Tributyltin hydride (Bu3SnH), has been successfully devised. Herein, we present a pioneering and uncomplicated methodology for the fabrication of tetracyclic 11H-benzo [4,5] imidazo[2,1-a] isoindole derivatives. This synthesis entails a sequence of inert Csp2-X/Csp2-H functionalization processes applied to N-cyano groups, followed by the radical cyclization of iminyl motifs. This study represents a significant advancement in the intramolecular radical cascade cyclization reaction of cyanamides, enabling the efficient synthesis of 1,2-disubstituted benzimidazole molecules, specifically the 11H-benzo [4,5] imidazo[2,1-a] isoindol and its analogues, achieved with yields ranging from 42% to 86%. Notably, this approach has been instrumental in the synthesis of a diverse array of compounds, establishing their efficacy as potent antibreast cancer agents. Furthermore, the proposed mechanism has been meticulously elucidated through a series of control experiments.