FeBr₃-Mediated Heteroannulation Route to Yield N-Amino-3-Nitrile-Indoles

Significance

Reported is the iron(III) bromide mediated intramolecular cyclization of 2-aryl-3-substituted hydrazono alkylnitriles to N-amino-3-nitrile-indoles. The starting hydrazones are easily prepared by condensation of the corresponding ketone and 1,1-dimethylhydrazine or N-amino­phthalimide. 1,1-Dimethylhydrazones bearing Bn or Ph groups (R^²) could not be prepared by direct treatment of 1,1-dimethylhydrazine with the corresponding ketones. This limitation was addressed by switching to N-aminophthalimide, which underwent condensation to give the starting hydrazones and gave, under the iron(III) bromide conditions, N-phthalimide-substituted 3-nitrile-indoles. Hydrazine-based phthalimide deprotection was demonstrated to give N-amino indoles in good yield, which substantially increases the value of this methodology. A SET-based mechanism proceeding through a nitrenium ion was postulated for the cyclization, but without evidence.