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The density functional theory study of the thermal C–C reductive coupling from terminal cyanido and hypothetical cyaphido complexes of [Ni(dmpe)] (dmpe = 1,2-bis(dimethylphosphino)ethane) revealed the key reaction intermediate in the reductive C–CP coupling being a σ-CC complex unlike an η2-aryl complex in the Ni C–CN system, as already observed in our previous studies. The reaction in THF is endothermic by 4.9 kcal/mol for cyanido with a 32.0 kcal/mol activation barrier and exothermic by 28.5 kcal/mol for cyaphido with an 11.3 kcal/mol activation barrier. To compare our results with the existing experimental data, we chose mesityl as the aryl group and also studied the CP reaction with [Pt(dmpe)] and [Pt(dmpm)] (dmpe = 1,2-bis(dimethylphosphino)methane) fragments. Our findings are consistent with the thermodynamically uphill photolytic C–CP bond activation in phosphaalkynes with Pt and a faster thermal back-reaction with [Pt(dmpe)] compared to that of [Pt(dmpm)]. Based on the natural population analysis, when the polarity of the C–C bond is inverted, the sign of ΔG°is also inverted.

A recent study of the oxidative addition of zerovalent Ni to the C–CN bond of F-substituted benzonitriles showed significantly increased stabilization of the C–CN oxidative addition products with o-F groups (−6.6 kcal/mol per o-F) compared to m-F groups (−1.8 kcal/mol per m-F). To answer the question of whether this is an o-F effect or an orthoeffect, in this study the effect of CF3and CH3groups on the oxidative addition of the [Ni(dmpe)] fragment [dmpe = 1,2-bis(dimethylphosphino)ethane] to the C–CN bond of benzonitriles has been studied. A density functional theory study of the reaction pathway between η2-CN complexes and the C–CN oxidative addition products shows stabilization of the C–CN oxidative addition product with the electron-withdrawing CF3group and destabilization with the electron-donating CH3group in both tetrahydrofuran and toluene. There is a slightly larger orthoeffect with CF3(−7.4 kcal/mol) than with F. However, due to steric crowding, two o-CF3groups did not show considerably more stabilization than one o-CF3group. There is a linear relationship between ΔG°and the number of metagroups (2.0 kcal/mol stabilization per m-CF3and 0.8 kcal/mol destabilization per m-CH3). On the basis of natural population analysis, as the C–CN bond becomes more polarized, the stability of the C–CN oxidative addition products with respect to the η2-CN complexes increases.

Heteroaryl compounds are valuable building blocks in medicinal chemistry and chemical industry. A palladium-catalyzed direct α-C(sp3) heteroarylation of ketones under microwave irradiation is developed and reported in this study. Under optimized conditions, twenty-eight (28) heteroarylated ketones were prepared in this study to demonstrate the substrate scope of this reaction. The ground-state optimized structure of Pd(0) active catalyst with 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) in toluene, and the products of its reaction with 3-bromopyridine and acetophenone were studied using all-atom density functional theory. This study provided insightful information for palladium catalytic system design to generate heteroaryl compounds.

The effect of fluoro substitution on the C–C bond activation of aromatic nitriles has been studied by reacting a variety of fluorinated benzonitriles with the nickel(0) fragment [Ni(dippe)] and by locating the reaction intermediates and transition-state structures on the potential energy surface by using density functional theory calculations with the [Ni(dmpe)] fragment (dippe = 1,2-bis(diisopropylphosphino)ethane, dmpe = 1,2-bis(dimethylphosphino)ethane). As in the previous reports, the reaction of fluorinated benzonitriles with the [Ni(dippe)] fragment initially formed an η2-nitrile complex, which then converted to the C–CN bond activation product. Thermodynamic parameters for the equilibrium between these complexes have been determined experimentally in both a polar (tetrahydrofuran) and a nonpolar (toluene) solvent for 3-fluoro- and 4-fluorobenzonitrile. The stability of the C–C bond activation products is shown to be strongly dependent on the number of ortho-F substituents (−6.6 kcal/mol per o-F) and only slightly dependent on the number of meta-F substituents (−1.8 kcal/mol per m-F).