Selective functionalization of 2-fluoropyridine, 2,3-difluoropyridine, and 2,5-difluoropyridine at each vacant position

The concept of "regioexhaustive substitution" has been successfully applied to 2-fluoro-, 2,3-difluoro-, and 2,5-difluoropyridine. All vacant positions were amenable to regioselective metalation and subsequent carboxylation by employing either chlorine as a neighboring site activating protective group or trimethylsilyl. as a neighboring site screening protective group. In this way, approximately half a dozen fluorinated pyridinecarboxylic acids were derived from each starting material.