Synthesis of Tricyclic Aminopyridines by a Cadmium Promoted Cyclization

Article abstract of DOI:10.1021/jo00121a048

A novel cyclocondensation of o-amino nitriles with cyclic 1,3-diones has been developed as a synthetic route to assemble fused tricyclic aminopyridine derivatives.The reaction sequence involves the initial formation of an enaminone.The enaminone is then cyclized at 120 deg C to 190 deg C in the presence of Lewis acids which include zinc, cadmium and copper(I) salts.The cyclization may be promoted under more mild conditions by first deprotonating the enaminone to form the anion followed by exposure to cadmium(II) salts at 60 deg C to 90 deg C.Alternatively, the enaminones may be reacted with organocadmium reagents such as dibutylcadmium to effect the deprotonation and cyclization directly at room temperature.Synthetic applications of these novel cadmium-mediated cyclizations are presented and mechanistic considerations discussed.