Construction of Tetrahydropyridobenzimidazoles via Ni–Al Bimetal-Catalyzed Tandem C(sp2)/C(sp3)–H Annulation

Abstract

Tetrahydropyridobenzimidazoles are privileged heterocyclic motifs prevalent in bioactive molecules. While transition-metal-catalyzed C–H annulation of benzimidazoles has emerged as a highly atom-economical approach, current strategies are largely limited to single C–H and dual C(sp2)–H annulation; these systems afford (hydro)pyridobenzimidazoles but cannot access tetrahydropyrido-fused analogues, because they are hampered by the low reactivity of aliphatic C(sp3)–H bonds. Herein, we report a tandem C(sp2)–H/C(sp3)–H annulation of N-alkyl benzimidazoles with alkynes enabled by a phosphine oxide-ligating Ni–Al bimetallic catalyst, furnishing various tetrahydropyridobenzimidazoles in 40–98% yields from readily available starting materials.