Access to Highly Substituted 7-Azaindoles from 2-Fluoropyridines via 7-Azaindoline Intermediates

Org Lett. 2015 Sep 4;17(17):4292-5. doi: 10.1021/acs.orglett.5b02098. Epub 2015 Aug 20.

Abstract

A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2-fluoro-3-(2-nitroethyl)pyridines. A facile oxidative Nef reaction/reductive amination/intramolecular SNAr sequence furnishes 7-azaindolines. Finally, optional regioselective electrophilic C5-substitution (e.g., bromination or nitration) and subsequent in situ oxidation delivers highly functionalized 7-azaindoles in high overall efficiency.