Ortho-Fluoro Effect on the C–C Bond Activation of Benzonitrile Using Zerovalent Nickel

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)

DFT Investigation of para-Substituent Effects on the C—C Bond Activation of Benzonitrile by a Zerovalent Nickel Complex

C—C bond activation has been an active area of research due to its extensive range of applications in in industry and synthesis. Despite its significance, the cleavage of a C—C bond has been challenging due to the thermodynamic stability and steric hindrance of C—C σ-bonds. In this study, density functional theory (DFT) calculations on the C—CN bond activation of para-substituted benzonitriles, p-XC6H4CN, where X= NH2, OCH3, CH3, H, F, CO2CH3 CF3 and CN, with the [Ni(dmpe)] fragment as a model for [Ni(dippe)] fragment will be reported. A comparison of the computational results with the previously reported experimental results and the natural bond analysis (nbo) on the η2-nitrile complexes and the Ni(II) oxidative addition products will also be presented

Etheric C–O Bond Hydrogenolysis Using a Tandem Lanthanide Triflate/Supported Palladium Nanoparticle Catalyst System

Selective hydrogenolysis of cyclic and linear ether C–O bonds is accomplished by a tandem catalytic system consisting of lanthanide triflates and sinter-resistant supported palladium nanoparticles in an ionic liquid. The lanthanide triflates catalyze endothermic dehydroalkoxylation, while the palladium nanoparticles hydrogenate the resulting intermediate alkenols to afford saturated alkanols with high overall selectivity. The catalytic C–O hydrogenolysis is shown to have significant scope, and the C–O bond cleavage is turnover-limiting

Rapid Ether and Alcohol C–O Bond Hydrogenolysis Catalyzed by Tandem High-Valent Metal Triflate + Supported Pd Catalysts

The thermodynamically leveraged conversion of ethers and alcohols to saturated hydrocarbons is achieved efficiently with low loadings of homogeneous M­(OTf)_<i>n</i> + heterogeneous Pd tandem catalysts (M = transition metal; OTf = triflate; <i>n</i> = 4). For example, Hf­(OTf)₄ mediates rapid endothermic ether ⇌ alcohol and alcohol ⇌ alkene equilibria, while Pd/C catalyzes the subsequent, exothermic alkene hydrogenation. The relative C–O cleavage rates scale as 3° > 2° > 1°. The reaction scope extends to efficient conversion of biomass-derived ethers, such as THF derivatives, to the corresponding alkanes

Reaction Pathways and Energetics of Etheric C–O Bond Cleavage Catalyzed by Lanthanide Triflates

Efficient and selective cleavage of etheric C–O bonds is crucial for converting biomass into platform chemicals and liquid transportation fuels. In this contribution, computational methods at the DFT B3LYP level of theory are employed to understand the efficacy of lanthanide triflate catalysts (Ln­(OTf)₃, Ln = La, Ce, Sm, Gd, Yb, and Lu) in cleaving etheric C–O bonds. In agreement with experiment, the calculations indicate that the reaction pathway for C–O cleavage occurs via a C–H → O–H proton transfer in concert with weakening of the C–O bond of the coordinated ether substrate to ultimately yield a coordinated alkenol. The activation energy for this process falls as the lanthanide ionic radius decreases, reflecting enhanced metal ion electrophilicity. Details of the reaction mechanism for Yb­(OTf)₃-catalyzed ring opening are explored in depth, and for 1-methyl-<i>d</i>₃-butyl phenyl ether, the computed primary kinetic isotope effect of 2.4 is in excellent agreement with experiment (2.7), confirming that etheric ring-opening pathway involves proton transfer from the methyl group alpha to the etheric oxygen atom, which is activated by the electrophilic lanthanide ion. Calculations of the catalytic pathway using eight different ether substrates indicate that the more rapid cleavage of acyclic versus cyclic ethers is largely due to entropic effects, with the former C–O bond scission processes increasing the degrees of freedom/particles as the transition state is approached

Palladium-Catalyzed C8-Selective C–H Arylation of Quinoline <i>N</i>‑Oxides: Insights into the Electronic, Steric, and Solvation Effects on the Site Selectivity by Mechanistic and DFT Computational Studies

We report herein a palladium-catalyzed C–H arylation of quinoline <i>N</i>-oxides that proceeds with high selectivity in favor of the C8 isomer. This site selectivity is unusual for palladium, since all of the hitherto described methods of palladium-catalyzed C–H functionalization of quinoline <i>N</i>-oxides are highly C2 selective. The reaction exhibits a broad synthetic scope with respect to quinoline <i>N</i>-oxides and iodoarenes and can be significantly accelerated to subhour reaction times under microwave irradiation. The C8-arylation method can be carried out on a gram scale and has excellent functional group tolerance. Mechanistic and density functional theory (DFT) computational studies provide evidence for the cyclopalladation pathway and describe key parameters influencing the site selectivity

Axial Ligand Exchange of <i>N</i>‑heterocyclic Cobalt(III) Schiff Base Complexes: Molecular Structure and NMR Solution Dynamics

The kinetic and thermodynamic ligand exchange dynamics are important considerations in the rational design of metal-based therapeutics and therefore, require detailed investigation. Co­(III) Schiff base complex derivatives of bis­(acetylacetone)­ethylenediimine [acacen] have been found to be potent enzyme and transcription factor inhibitors. These complexes undergo solution exchange of labile axial ligands. Upon dissociation, Co­(III) irreversibly interacts with specific histidine residues of a protein, and consequently alters structure and causes inhibition. To guide the rational design of next generation agents, understanding the mechanism and dynamics of the ligand exchange process is essential. To investigate the lability, pH stability, and axial ligand exchange of these complexes in the absence of proteins, the pD- and temperature-dependent axial ligand substitution dynamics of a series of <i>N</i>-heterocyclic [Co­(acacen)­(X)₂]⁺ complexes [where X = 2-methylimidazole (2MeIm), 4-methylimidazole (4MeIm), ammine (NH₃), <i>N</i>-methylimidazole (NMeIm), and pyridine (Py)] were characterized by NMR spectroscopy. The pD stability was shown to be closely related to the nature of the axial ligand with the following trend toward aquation: 2MeIm > NH₃ ≫ 4MeIm > Py > Im > NMeIm. Reaction of each [Co­(III)­(acacen)­(X)₂]⁺ derivative with 4MeIm showed formation of a mixed ligand Co­(III) intermediate via a dissociative ligand exchange mechanism. The stability of the mixed ligand adduct was directly correlated to the pD-dependent stability of the starting Co­(III) Schiff base with respect to [Co­(acacen)­(4MeIm)₂]⁺. Crystal structure analysis of the [Co­(acacen)­(X)₂]⁺ derivatives confirmed the trends in stability observed by NMR spectroscopy. Bond distances between the Co­(III) and the axial nitrogen atoms were longest in the 2MeIm derivative as a result of distortion in the planar tetradentate ligand, and this was directly correlated to axial ligand lability and propensity toward exchange