In the presence of a catalytic amount of Cp*RuCl(cod), 1,6-diynes were allowed to react chemo- and regioselectively with electron-deficient nitriles and heterocumulenes at 60-90 degrees C to afford heterocyclic compounds. The mechanism of the ruthenium-catalyzed regioselective formations of bicyclic pyridines and pyridones were analyzed on the basis of density functional calculations. Cyclocotrimerizations of ethyl propiolate with ethyl cyanoformate or propyl isocyanate gave rise to two of the four possible pyridine or pyridone regioisomers.

In the presence of a catalytic amount of [Cp*RuCl(cod)] (Cp*=pentamethylcyclopentadienyl, cod=1,5-cyclooctadiene), 1,6-diynes were allowed to react chemo- and regioselectively with nitriles bearing a coordinating group, such as dicyanides or alpha-halonitriles, at ambient temperature to afford bicyclic pyridines. Careful screening of nitrile components revealed that a C[triple chemical bond]C triple bond or heteroatom substituents, such as methoxy and methylthio groups, proved to act as the coordinating groups, whereas C==C or C==O double bonds and amino groups failed to promote cycloaddition. This suggests that coordinating groups with multiple pi-bonds or lone pairs are essential for the nitrile components.

In the presence of a catalytic amount of Cp*RuCl(cod), 1,6- and 1,7-diynes connected by an amide or an ester tether underwent cycloaddition with terminal alkynes at room temperature to give rise to cycloadducts in 40-93% yields with 63 : 37-83 : 17 regioisomer ratios.

In the presence of 2 -5 mol % Cp*RuCl (cod), various 1,6-diynes reacted with a-monohaloand a,a-dihalonitriles at ambient temperature to afford 2-haloalkylpyridines in 42 -93% isolated yields. The failure of acetonitrile, N,N-dimethylaminoacetonitrile, phenylthioacetonitrile, and methyl cyanoacetate as nitrile substrate clearly showed that the a halogen substitution is essential for the present cycloaddition under mild conditions. The cycloaddition of unsymmetrical diynes bearing a substituent on one alkyne terminal gave 2,3,4,6-substituted pyridines exclusively.Keywords: alkynes; cyanides; cyclotrimerization; pyridines; rutheniumThe transition-metal-mediated [2 þ 2 þ 2] cyclocotrimerization of two alkynes and a nitrile is a powerful and straightforward route to substituted pyridines.[1] Although the catalytic cyclocotrimerization is becoming increasingly important as an environmentally benign process, the pair-and regio-selectivity as well as reaction conditions have remained to be largely improved compared to stoichiometric protocols. [2] In this context, mild and selective catalytic cycloadditions of a,w-diynes with nitriles were recently achieved by means of a chiral indenylcobalt complex and a nickel N-heterocyclic carbene complex.[3] In particular, the former catalyst proved to be effective toward the asymmetric synthesis of axially chiral pyridines. In addition, novel intramolecular protocols were recently developed to synthesize pyridine-containing macrocycles or 2-aminopyridines. [4] We have also developed independently the Cp*RuClcatalyzed cycloadditions of a,w-diynes with carbon-heteroatom multiple bonds, [5] and found that the dicyanides are exceptional nitrile substrates capable of undergoing cycloaddition even at ambient temperature.[6] In fact, in the presence of 5 mol % Cp*RuCl(cod) 1 (Cp* ¼ h 5 -C 5 Me 5 , cod ¼ 1,5-cyclooctadiene), the cycloaddition of dimethyl dipropargylmalonate (2a) with malononitrile (3a; R¼ CN) proceeded even at room temperature for 2.5 h to afford bicyclic pyridine 4aa (R ¼ CN) in 95% yield (Scheme 1). Although one of the two cyano groups remained intact after the reaction, the complete incompetence of acetonitrile provides the possibility of one cyano moiety as a coordinating group. To expand the scope of the nitrile substrate, other nitriles possessing a coordinating group a to the cyano group were further screened (Figure 1). Consequently, methyl cyanoacetate (3b; R ¼ CO 2 Me), N,N-dimethylaminoacetonitrile (3c; R¼ NMe 2 ), and phenylthioacetonitrile (3d; R¼ SPh) were found to be totally ineffective. In striking contrast, chloroacetonitrile (3e; R ¼ Cl) underwent cycloaddition with 2a in the presence of 2 mol % 1 at ambient temperature for 2 h to give rise to chloromethylpyridine 4ae in 93% isolated yield. [7] This result was quite surprising because trichloroacetonitrile, which underwent cycloaddition with 2a at 60 8C in our previous study, [5] failed to react at ambient temperature. These facts indicate that the observed reactivity enhancement is not ascribed...

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