Further metalations and functionalizations of chloro-, bromo- and iodo(trifluoromethyl)pyridines

In accordance with the concept of regioexhaustive functionalization, both 3-chloro-2-(trifluoromethyl)pyridine and 2-bromo-6-(trifluoromethyl)pyridine were converted each time into the three possible carboxylic acids (1, 4 and 5 and 6, 9 and 12, respectively). 2-Bromo-4-(trifluoromethyl)pyridine, 2-bromo-5-(trifluoromethyl)pyridine, 2-iodo-4-(trifluoromethyl)pyridine and 4-iodo2-(trifluoromethyl)pyridine were selectively deprotonated and subsequently carboxylated at the respective 3-positions thus affording the acids 13-16. Finally, the N-pivaloyl-protected 2-amino-3-chloro-5-(trifluoromethyl)pyridine was deprotonated at the 4-position and the intermediate trapped with iodine and benzaldehyde to provide, after amide cleavage, the aminopyridines 17 and 18.