Visible-light-promoted late-stage direct fluoroalkylation of nitroimidazoles

Abstract

Incorporation of fluoroalkyl groups into bioactive compounds can dramatically change their physicochemical and physiological properties, and further improve their pharmacokinetic as well as pharmacological profiles. Therefore, the fluoroalkylation has been acknowledged as a vital strategy in medicinal chemistry for drug discovery. In this study, an efficient and convenient method for the preparation of fluoroalkylated nitroimidazoles through visible-light-prompted direct radical reaction with commercially available materials is described. The strategy proceeds smoothly under mild conditions to afford the fluoroalkyl nitroimidazoles under mild conditions. In addition, control experiments have been performed, revealing a radical process involved in the reaction mechanism. Preliminary evaluations on some products display enhanced antibacterial activities, which further demonstrates the approach to be a versatile protocol for the late-stage fluoroalkylation of clinical drugs toward a diversity-oriented drug discovery.