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

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.

Automated summary

A simple and effective method for copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides using ethyl bromodifluoroacetate as the bifunctional reagent was developed. The combination of cupric catalyst and alkaline additive enables C5-bromination, while the combination of cuprous catalyst and silver additive enables C5-difluoromethylation. This method exhibits a wide substrate scope and provides easy access to desired C5-functionalized quinolones with high yields.