Synthesis of difluorinated pyridinecarboxaldehyde via electrophilic fluorination

An efficient synthesis of novel 3,5-difluoropyridine-4-carboxaldehyde using N-fluoro-benzenesulfonimide (NSFi) is described. Difluorination was achieved through the reaction of 3,5-dihalo-1,3-dioxolane pyridine with n-butyllithium followed by N-fluorobenzenesulfonimide at −120 °C in good to high yields. Maintaining the low temperature during the transmetallation was found to be critical for the selective formation of the difluoro-susbstitution over the monofluoro one.