title: A practical route to substituted 7-aminoindoles from pyrrole-3-carboxaldehydes.
abstract: Among privileged structures, indoles occupy a central place in medicinal chemistry and alkaloid research. Here we report a flexible and efficient conversion of pyrrole-3-carboxaldehydes to substituted 7-amino-5-cyanoindoles. Phosphine addition to fumaronitrile proceeds with prototropic rearrangement of the initially formed zwitterion to the thermodynamically favored phosphonium ylide, which is poised for in situ Wittig olefination. The predominantly E-alkene product positions the allylic nitrile for facile intramolecular Hoeben-Hoesch reaction in the presence of BF3·OEt2. Syntheses of 2,5- and 3,5-disubstituted 7-aminoindoles are illustrated. Additionally, dianion alkylation of the allylic nitrile is demonstrated to furnish, after cyclization, 5,6-disubstituted 7-aminoindoles to further exemplify this scalable and high-yielding method.
authors.affiliation: Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Victor K
authors.initials: VK
authors.lastname: Outlaw
authors.forename: Craig A
authors.initials: CA
authors.lastname: Townsend
mesh_terms: D000478:Alkylation; D002384:Catalysis; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D007211:Indoles; D009570:Nitriles; D011758:Pyrroles; C512101:5-aminoindole