The combination of Fe(OAc)2 and an electron-donating, sterically-hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles and alkynes. A variety of substituted pyridines were obtained in good yields.

Diynes and cyanamides undergo an iron-catalyzed [2+2+2] cycloaddition to form highly substituted 2-aminopyridines in an atom-efficient manner that is both high yielding and regioselective. This system was also used to cyclize two terminal alkynes and a cyanamide to afford a 2,4,6-trisubstituted pyridine product regioselectively.

Inductive perturbations of C-C triple bonds are shown to dictate the regiochemistry of gold-catalyzed oxidation of internal C-C triple bonds in the cases of propargylic ethers, resulting in highly regioselective formation of β-alkoxy-α,β-unsaturated ketones (up to >50/1 selectivity) via α-oxo gold carbene intermediates. Ethers derived from primary propargylic alcohols can be reliably transformed in good yields, and various functional groups are tolerated. With substrates derived from secondary propargylic alcohols, the development of a new P,N-bidentate ligand enables the minimization of competing alkyl group migration to the gold carbene center over the desired hydride migration; the preferred migration of a phenyl group, however, results in efficient formation of a α-phenyl-β-alkoxy-α,β-unsaturated ketone. These results further advance the surrogacy of a propargyl moiety to synthetically versatile enone function with reliable and readily predictable regioselectivity.

Several cycloaddition catalysts and reagents were surveyed for their effectiveness toward cyclizing alkynenitriles with cyanamides. Catalytic amounts of FeI2, iPrPDAI and Zn were found to effectively catalyze the [2+2+2] cycloaddition of a variety of cyanamides and alkynenitriles to afford bicyclic 2-aminopyrimidines.

A mild and general route for preparing dieneamides is described. Ni imidazolylidene complexes were used to mediate cycloadditive couplings between enynes and isocyanates. Dienamides were prepared in excellent yields and with good E:Z selectivity. These dieneamides can be further manipulated through oxidative cyclization methods. When a terminal enyne is employed, cyclization affords a lactam rather than a dienamide.A primary interest of our group is the development of efficient cycloadditions that afford heterocycles and carbocycles. [1][2][3][4][5][6][7] We have found that Ni/NHC complexes effectively catalyze the cycloaddition of diynes with CO 2 ,2 isocyanates, 3 carbonyls, 4 and nitriles. 5 These reactions afford pyrones, pyridones, pyrimidinones, pyrans, and pyridines in high yields. In addition, the same Ni/NHC system also mediates the rearrangement of vinyl cyclopropanes 6 and cyclopropylen-ynes. 7 The efficacy of our Ni/NHC catalyzed cycloaddition reactions that couple diynes/ isocyanates 3 and enynes/carbonyls 4 prompted us to investigate the Ni/NHC catalyzed cycloaddition of enynes and isocyanates. To date, only one catalytic system, which utilizes Rh catalysts, effectively cyclizes an olefin, an alkyne, and an isocyanate. This Rh catalyst was used to couple an alkenyl-isocyanate with an alkyne in the synthesis of Lasubine alkaloids. 8 Herein, we report our investigations involving the Ni catalyzed reactions between enynes and isocyanates to afford dieneamides.Despite the precedent that enynes and isocyanates were both viable substrates individually in the Ni catalyzed cycloaddition reaction, it was unclear whether they would react with each other in a productive manner. However, success in Ni catalyzed reductive couplings between alkenes and alkyl-substituted isocyanates 9 suggested enynes and isocyanates would be reactive under Ni catalyzed cycloaddition reaction conditions. Our initial efforts revolved around evaulating a variety of conditions that would yield an isolable product. As shown in Table 1, a variety of phosphines and NHCs 10 were evaluated as prospective ligands to determine the potential reactivity between enyne (1a) and cyclohexyl isocyanate (2a , Equation 1). Attention was directed toward minimizing alkyne