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Iodine‐Catalyzed Metal‐Free Oxidative Ring Opening of 1‐Aryltetrahydro‐β‐carbolines: Facile Synthesis of C‐2 Aroyl and Aryl Methanimino Indole Derivatives
Author(s) -
Chauhan Jyoti,
Luthra Tania,
Sen Subhabrata
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800879
Subject(s) - chemistry , indole test , catalysis , hydrogen peroxide , aryl , luzindole , combinatorial chemistry , ring (chemistry) , benzimidazole , organic chemistry , medicinal chemistry , melatonin receptor , receptor , biochemistry , alkyl
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.