Metal-free site-selective C–N bond-forming reaction of polyhalogenated pyridines and pyrimidines

Abstract

This paper presents a metal-free method for highly site-selective C–N bond-forming reaction of polyhalogenated pyridines and pyrimidines. The preferred coupling site can be tuned from the fluorine group bearing the N-heterocyclic ring to the chlorine group when changing from the pyridine ring to the pyrimidine ring. A wide array of halogenated pyridines preferentially reacted with amines at the fluorine group of the pyridine ring to generate monosubstituted halogenated pyridines with high selectivities. Different halogen atoms at various positions were produced by the pyridine ring that performed well under mild conditions. Halogenated pyrimidines underwent highly selective coupling at the chloride group with a wide range of amines having broad substrate applicability and moderate to good yields. The selectivity of the polyfluoropyridines in the developed reaction system was also tested, and the result indicated that the reaction occurred site-selectively at the ortho-position of the nitrogen ring. This reaction accommodated a wide range of halogenated groups. Thus, a wide range of chloro-, bromo-, iodo-, and fluoropyridines were generated, which have a wide utility for organic synthesis.