Exploring nickel- and iron- catalyzed cycloaddition routes to N- heterocycles

Transition metal catalyzed [2+2+2] cycloaddition reactions are an important class of reactions that provide the means for the rapid construction of various carbocyclic and heterocyclic compounds. Over the past several years, our efforts have been focused on exploring metal catalyzed cycloaddition reactions to find new methods and improve existing methods to access heterocyclic core structures such as pyridines, pyridones and pyrimidones.;Enynes and isocyanates in the presence of a nickel-based catalyst system undergoes cycloaddition affording E- and the Z-dienamides in moderate to good yields with the E-dienamide being the major product. The substrate scope with respect to isocyanate and enyne structures was also determined. It was observed that aryl as well as alkyl isocyanates undergo this cycloaddition reaction. Internal enynes afforded the dienamide products while terminal enynes afforded lactams.;A new catalytic system involving iron acetate and a sterically hindered bis(aldimino)pyridyl ligand was also developed. This Fe-complex catalyzed the cycloaddition reaction of alkynenitriles and alkynes to afford pyridines in moderate to good yields. Symmetrical and unsymmetrical exogenous alkynes can be used in this cycloaddition reaction. Alkyl, aryl, and terminal alkynenitrile afford good yields of the pyridine products. Five- and six-membered fused pyridines can be synthesized in good yields by this methodology.;The synthesis of 2-aminopyridines by the cycloaddition reaction of diynes and cyanamides in the presence of an iron catalyst system has also been studied. The Fe-catalytic system is a combination of iron chloride and a bis(aldimino)pyridyl ligand and it leads to good to excellent yields of desired product. Five- and six-membered fused 2-aminopyridines were prepared in good yields by utilizing this methodology. Various N-alkyl-alkyl, N-aryl-aryl, and N-alkyl-aryl cyanamides undergo this cycloaddition reaction with diynes to afford 2-aminopyridines in good yields.