Title: A practical route to substituted 7-aminoindoles from pyrrole-3-carboxaldehydes.
Authors: Outlaw, Victor K; Townsend, Craig A
Published In Org Lett, (2014 Dec 19)
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.
PubMed ID: 25479249
MeSH Terms: Alkylation; Catalysis; Cyclization; Indoles/chemical synthesis*; Indoles/chemistry; Molecular Structure; Nitriles/chemistry*; Pyrroles/chemistry*; Stereoisomerism