Cyclization of 2-dicyanomethylene-1,2-dihydropyridine-3-carbonitriles with amines: a mechanistic rationalization

A mechanistic rationalization for the cyclization of the 1,5-dinitrile system present in pyridines 4{1-3} with amines to lead to 1,6-naphthyridines is proposed. Three factors play an important role on the direction of cyclization: (1) the cyclization involves nucleophilic attack of an amidine onto a nitrile or amidine; (2) the attack has to fulfill strict geometrical constraints to allow the cyclization to proceed; (3) the cyclization step should involve the nucleophilic attack combined with a tautomerism to achieve the high levels of regioselectivity observed.