Alcohol Dehydrogenation-Triggered Selective C3-Alkylation of Indoles by Homogeneous Azo-aromatic Cobalt Catalysts

Abstract

Herein, we report azo-benzimidazole containing cobalt complexes (1-3) for alcohol dehydrogenation-triggered C3-alkylation of indoles. In complexes 1-3, ligands are redox noninnocent and showed facile irreversible L/L• reduction followed by Co(II)/Co(I) reduction in close-lying potentials. Taking advantage of facile redox events in 1-3, the first aerial dehydrogenation of alcohols to their corresponding carbonyl compounds is explored. Subsequently, C3-alkylation of indole was studied using alcohols as the alkylating agents. The developed catalytic protocol was found to be efficient and very selective. It has a broad substrate scope and good functional group tolerance. As far as we are aware, it is the first homogeneous cobalt catalyst for C3-alkylation of indole using alcohol as the alkylating agent. Detailed mechanistic studies, including a deuterium labeling experiment, have suggested a borrowing hydrogen method for the C3-alkylation of indole. The coordinated ligand, cooperatively with the Co(II)/Co(I) redox couple, oxidized the coordinated alkoxide in a radical pathway to result in the carbonyl compound (Scheme 1), which on subsequent condensation with indole generates the alkylideneindolenine intermediate “X”. Reduction of “X” by an azo-anion radical Co(I) catalyst intermediate resulted in the C3-alkylated indole. © 2023 American Chemical Society.