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--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.