Amine Directed Pd(II)-Catalyzed C–H Activation-Intramolecular Amination of N‑Het(aryl)/Acyl Enaminonitriles and Enaminones: An Approach towards Multisubstituted Indoles and Heterofused Pyrroles

• Published in: Journal of organic chemistry 2016-03, Vol.81 (5), p.2035-2052
• Main Authors: Yugandar, Somaraju, Konda, Saidulu, Ila, Hiriyakkanavar
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b02902

An efficient route to multisubstituted indoles has been developed through intramolecular oxidative C–H activation-amination of readily available 2-(het)­aryl-3-(het)­aryl/alkyl-3-(het)­aryl/acylaminoacrylonitrile/enaminone precursors in the presence of either palladium acetate/cupric acetate catalytic system under oxygen atmosphere or palladium acetate/silver carbonate in the presence of pivalic acid as additive. The method is compatible with a diverse range of substituents on the aryl ring as well as at the 2- and 3-positions of the indole ring. The versatility of this method was further demonstrated by elaborating it for the synthesis of heterofused pyrroles such as thieno­[2,3-b]­pyrroles, thieno­[3,2-b]­pyrroles, pyrrolo­[2,3-b]­indoles, and pyrrolo­[2,3-b]­pyridines in good yields. Probable mechanisms for the formation of these indoles have been suggested.