Regioselective Electrophilic Fluorination of Rationally Designed Imidazole Derivatives

We report the regioselective and direct functionalization of rationally designed imidazole derivatives through electrophilic fluorination with N-fluorobenzenesulfonimide enabled via in situ deprotonation with lithium 2,2,6,6-tetramethylpiperidine. Aided by a controlled protecting group switch, we were able to effectively target both the reactive 5- as well as the difficult to target 4-position of these molecules, leading to a series of fluorinated polysubstituted imidazoles in gram scale.