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A computational study was conducted to investigate the mechanism of a new type of C–N bond metathesis reaction, in which a reversible reductive elimination/oxidative addition mode is involved.

Density functional theory (DFT) calculations have been performed to provide mechanistic insight into the Rh/Cu co-catalyzed multicomponent annulation of indoles, diazo compounds, and α,β-unsaturated esters. Indole can undergo electrophilic attack by a dirhodium–carbene complex to form a cyclopropane intermediate, which is transferred to an enolate by deprotonation. A dimetallic Michael-type addition reaction is proposed by DFT calculation, where the diastereoselectivity is controlled by the interaction energy between the incoming α,β-unsaturated ester and enolate nucleophile. In copper catalysis, an intramolecular oxidation by copper enolate/copper ketonate resonance is revealed, by which copper enolate is partially oxidized to an α-carbonyl radical. Therefore, intramolecular radical addition with the indole moiety achieves annulation with the formation of a C3 radical in dearomatic indole. Oxidative hydrogen atom transfer then gives the aromatic annulation product by using excess copper chloride.

While the mechanisms of transition metal-catalyzed coupling reactions have received extensive attention, the extent to which these apply to catalytic Alder-ene-type reactions remains unclear. A novel 1,5-H shift mechanism for a Ru-catalyzed Alder-ene type alkene–alkyne coupling reaction was examined by density functional theory (DFT). This reaction begins with a cyclometallation between alkene and alkyne to form a ruthenacyclopentene. Then, 1,5-H shift generates an olefin coordination intermediate. Sequential ligand exchanges construct the final product and regenerate the active catalyst. Results show that a pathway through a [3 + 2] cyclometallation and 1,5-H shift step is favored over the traditional cycloaddition – β-hydride elimination and reductive elimination route reported previously. The stereoselectivity of the product is also validated and the results show that it is predominately controlled by the energy differences in both the cyclometallation and the 1,5-H shift step. Regioselectivity is mainly controlled by electronic effect and six-membered ring tension.

Nickel-catalyzed C–H bond activation has attracted significant attention for the construction of C–C bond frameworks. We report density functional theory investigations into the mechanism of nickel-catalyzed alkylation of benzamides with alkyl halides. Both the Ni(I)–Ni(III) and Ni(II)–Ni(IV) catalytic cycles were considered. The theoretical study indicated that the most feasible mechanism involved a Ni(II)–Ni(IV) catalytic cycle with four main steps: (i) N–H bond activation and (ii) C–H bond activation through the concerted metalation–deprotonation pathway, (iii) oxidative addition of BuBr to give a high-valent Ni(IV) complex, and (iv) C–C reductive elimination to generate the product and the active catalyst. The rate-determining step of the favored pathway is the oxidative addition, leading to the generation of a Ni(IV) intermediate. In addition, the present study casts light on the role of PPh3, which accelerates the cleavage of N–H bond. Frontier molecular orbital theory and natural population analysis were employed to explain the effect of the phosphine ligand on the structure of the Ni complex.

The trifluoromethyl group (CF3) is a very important functional group. The mechanism of transition metal catalyzed trifluoromethylation has received considerable attention in recent years. In this work, the detailed mechanism of the copper-catalyzed oxytrifluoromethylation of allylamines with CO2 was investigated by density functional theory (DFT) calculations. Differing from the previous Cu(I)–Cu(III) catalytic cycle, the results show that the reaction proceeds through a Cu(I)–Cu(II) catalytic cycle. Deprotonation of allylamines initially occurs with the assistance of a copper catalyst followed by CO2 insertion. In the presence of Togni reagent II, the copper(I) carboxylate species can then be oxidized to the copper(II) dicarboxylate intermediate along with the formation of a free trifluoromethyl radical, which then attacks the alkene moiety to generate the electrophilic addition diradical adduct. The spiro ring is constructed by a carboxylate-delivered radical–radical cross-coupling procedure. In addition, the calculated global electrophilicity shows that the copper(III) intermediate cannot be generated from the combination of the electron deficient copper center and the electrophilic trifluoromethyl radical. Frontier molecular orbital analysis indicates that the Togni reagent II is activated by neutral Cu(I) rather than the cationic Cu(I) species. The origin of the diastereoselectivity can be mainly attributed to the repulsion between the trifluoromethyl group and the carbonyl moiety.

The density functional theory (DFT) method M06-L was used to study the general mechanism of palladium-catalyzed C–S bond formation reactions. Our theoretical calculations revealed that this type of reaction starts with a palladium-assisted metalation–deprotonation step. Oxidative addition of the sulfur source affords a thiolate–palladium(IV) intermediate, and subsequent reductive elimination generates the new C–S bond. A final protonation regenerates the active palladium(II) catalyst and releases the product. Our proposed mechanism could be applied to a series of palladium-catalyzed C–S bond formation reactions used for the construction of dibenzothiophene derivatives. The rate-limiting step of the catalytic cycle is oxidative addition to yield the thiolate–palladium(IV) intermediate. In contrast, formation of a sulfonium intermediate is unfavourable. In addition, the effect of substituents on the rate-determining step was studied with Hammett plots. Our calculations showed that incorporation of electron-withdrawing groups at the 4-position and electron-donating groups at the 15 and 16-positions would promote intramolecular oxidative addition of thioethers to palladium.

In situ X-ray absorption spectroscopy (XAS), infrared (IR) and nuclear magnetic resonance (NMR) techniques were used to identify the structures and reactivity of copper-containing active intermediates in the sp2 C–H bond cleavage reaction of electron-deficient aromatics. An ate-complex [Cu(OtBu)2]Na was found to be able to cleave the C–H bond of benzothiazole (ArH) producing [ArCuI(OtBu)]Na with a rate constant of 3.2 × 10−2 mol−1 L s−1 at −50 °C and with an activation enthalpy of 0.73 kcal mol−1 at room temperature.