Copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides using ethyl bromodifluoroacetate as the bifunctional reagent.

Abstract

A simple and effective method for the copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides with ethyl bromodifluoroacetate as the bifunctional reagent was developed. The combination of cupric catalyst and alkaline additive results in a C5-bromination reaction, whereas cuprous catalyst combined with silver additive results in the C5-difluoromethylation reaction. This method has a broad substrate scope and allows for easy and convenient access to desired C5-functionalized quinolones with good to excellent yields.