Palladium-catalyzed amination of 3,5-dihalopyridines - A convenient route to new polyazamacrocycles

Pd-Catalyzed amination of 3,5-dibromo- and 3,5-dichloropyridine (1a and 1b, resp.) with linear polyamines 2 leads to the formation of a new family of pyridine-containing macrocycles 3 with an ‘exo’-oriented pyridine N-atom (Schemes 1 and 2). The dependence of the macrocycle yield on the nature of the halogen atom, the length of the polyamine chain and C/N atom ratio, and the composition of the catalytic system is studied. The synthesis of mono- and bis(5-halopyridin-3-yl)-substituted polyamines 4, 5, 8, 9, and of 3,5-bis(polyamino)-substituted pyridines 6 is described (Schemes 3 and 4), and the use of these compounds as intermediates on the way to the macrocycles 7, 16, and 18 with larger cavity (‘cyclodimers’ and ‘cyclotrimers’) is demonstrated (Schemes 5–10).