Iodine‐Catalyzed Metal‐Free Oxidative Ring Opening of 1‐Aryltetrahydro‐β‐carbolines: Facile Synthesis of C‐2 Aroyl and Aryl Methanimino Indole Derivatives

Indole derivatives bearing C‐2 substituents have garnered a lot of attention due to their diverse biological activities. Various methods forthe synthesis of these compounds have been reported. Inspired by the hydrolysis of imines, an oxidative ring‐opening reaction of 1‐aryltetrahydro‐β‐carbolines with catalytic iodine in aqueous hydrogen peroxide, and also in the presence of appropriate amines, is described for the generation of 2‐aroyl and arylmethanimine indole derivatives. The reaction proceeds under mild reaction conditions with ethanol as the solvent or under solvent‐free conditions, respectively. This metal‐free strategy facilitates the formation of the desired substituted C‐2 indoles in moderate to excellent yields. The utility of this reaction is demonstrated by a facile multigram‐scale synthesis of Luzindole, a selective melatonin receptor antagonist and an investigational drug against depression and disruption of the circadian rhythm.