Removal of Fluorine from and Introduction of Fluorine into Polyhalopyridines: An Exercise in Nucleophilic Hetarenic Substitution

Starting from six industrially available fluorinated pyridines, an expedient access to all three tetrafluoropyridines (2-4), all six trifluoropyridines (5-10), and the five non-commercial difluoropyridines (11-14 and 16) was developed. The methods employed for the selective removal of fluorine from polyfluoropyridines were the reduction by metals or complex hydrides and the site-selective replacement by hydrazine followed by dehydrogenation-dediazotation or dehydrochlorination-dediazotation. To introduce an extra fluorine atom, a suitable precursor was metalated and chlorinated before being subjected to a chlorine/fluorine displacement process.