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α-Carbonyl cations are the umpolung forms of the synthetically fundamental α-carbonyl carbanions. They are highly reactive yet rarely studied and utilized species and their precursors were rather limited. Herein, we report the generation of α-carbonyl cations from HNTf2-catalyzed alkyne oxidations with pyridine N-oxides and the interception of them via Wagner-Meerwein rearrangement. Broad spectrum of alkynes including aryl alkyne, ynamide, and alkynyl sulfide could be utilized and the migrating priorities of different groups in the Wagner-Meerwein rearrangement step was elucidated. DFT calculations further supported the generation of α-carbonyl cations via the N-O bond cleavage. Another key feature of this methodology was the fragmentation of synthetically inert tert-butyl groups into readily transformable olefin functionalities. The synthetic potential was highlighted by the scale-up reaction and the downstream diversifications including the formal synthesis of nicotlactone B and galbacin.

Nickel catalysis has recently emerged as an important addition to the suite of transition metal-catalysed C-H bond functionalization methods. Here we report density functional theory calculations to elucidate the mechanism of Ni(II)-catalysed C–H arylation with a diaryliodonium salt or a phenyliodide. The effect of the choice of oxidant on the order of oxidative addition and C–H bond cleavage is investigated. When the active catalyst is oxidized by the diaryliodonium salt oxidant, C–H bond cleavage occurs to give an alkyl-aryl-Ni(IV) species. Conversely, the relatively weak oxidant phenyliodide leads to an alternative reaction sequence. The active catalyst first undergoes C–H bond cleavage, followed by oxidative addition of the phenyliodide to give a Ni(IV) species. Frontier molecular orbital analysis demonstrates that the reaction sequence of oxidative addition and C–H bond cleavage is determined by the unoccupied Caryl–I bond antibonding orbital level of the oxidant. Nickel-catalysed C-H functionalisation reactions are of increasing importance. Here the mechanism of Ni(II)-catalysed C-H arylation of amides is shown to depend on the nature of the oxidant and in particular the energy of its Caryl-I antibonding orbital.

This study investigated the impact of pH on the efficiency of ferrate (Fe(VI), K2FeO4) toward fluoroquinolone antibiotics, built kinetic models of Fe(VI) oxidation, and elucidated the involved active species during Fe(VI) oxidation at acidic and alkaline conditions. It was found that the second-order reaction rate constants (kapp, M-1 s-1) of Fe(VI) with three fluoroquinolone antibiotics (i.e., enroxacin, ofloxacin, and norfloxacin) were strongly dependent on pH, and kapp reached its maximum at pH about 6.5. The reactions between HFeO4-/H2FeO4 and neutral/protonated fluoroquinolone antibiotics (X and XH+) were the major ones. Moreover, the reactive species were identified as high-valent iron species, i.e., Fe(VI), Fe(V), and Fe(IV), in alkaline solution, while hydroxyl radicals was generated through Fenton or Fenton-like processes at acidic condition with limited contribution.

C–F bond functionalization still faces with great challenges in synthetic chemistry due to the inert nature of C–F bond in organic compounds. Herein, the newly reported DFT method M11-L was used to determine the mechanism of nickel catalyzed C–F/C–H bond cross coupling involving the C–F bond cleavage of flouroarenes and C–H bond functionalization of oxazoles. DFT calculations revealed that fluoride would stabilize the nickel(0) compound to afford an active nickel(0) ate-complex. With the assistance of fluoride, the oxidative addition of C–F bond to nickel(0) ate-complex would yield an active nickel(II) species, which is the rate-determining step in this catalytic cycle. The following C–H bond cleavage step would proceed via a direct deprotonation step under the attack of Bronsted base, to generate diarylnickel(II) species. Finally, reductive elimination step would occur to give the coupling product with regeneration of active nickel(0) ate-complex. In this pathway, we found that the relative free energies of nickel ate-complex species are more stable than commonly assumed neutral-nickel intermediates. This work could provide a new way for the mechanism study of inert C--F bond activation reactions.

Density functional theory calculations were performed to study the counterion effect and directing group effect in rhodium mediated concerted metalation deprotonation type C H bond activation of arenes. The use of different carboxylates as counterions results in changes to the activation energies over a narrow range. These changes are mainly attributed to the opposing effects of alkalinity and nucleophilicity of the substituted groups. The effects of directing groups were also considered. By introducing directing groups, the C H bond activation energy is greatly reduced. Our results show that different directing groups have similar effects and activation energies.

Density functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.

Density functional theory (DFT) calculations were employed to study the mechanism for copper-catalyzed trifluoromethylation of aryl boronic acids by Togni’s reagent. Computational results suggest that the catalytic cycle proceeds with the transmetallation between phenylboronic acid and copper(I) species, which generates a phenylcopper(I) intermediate. Subsequent coordination of Togni’s reagent and the electrophilic substitution of CF3 group to phenyl group finally afford the trifluoromethylation product through a concerted five-membered ring transition state. The transmetallation process with an activation free energy of 21.7 kcal/mol is determined to be the rate-determining step of this reaction. Moreover, the reactivity of alkylboronic acid was also calculated and proven to be unfavorable due to the higher activation free energy of transmetallation process.

Both theoretical and experimental studies were performed to explore the mechanism, regioselectivity, and enantioselectivity of phosphine-catalyzed [3 + 2] annulation between allenoates and acrylate or imine. Using density functional theory computations, we predicted that the enantioselective determining step is the nucleophilic addition of acrylate or imine to the catalyst-activated allenoate. In the key step, we proposed two hydrogen bonding interaction models (intermolecular H-bond model and intramolecular H-bond model). For acrylate substrates, the reaction proceeds via the intramolecular H-bond model and the strong noncovalent interactions between the 2-naphthyl ester moiety lead to the re-face attack pathway being more favorable. For imine substrates, the intermolecular H-bond model operates. In the annulation process, the bulky n-propyl oriented toward a crowded, sterically demanding environment plays a significant role in asymmetric induction. The theoretical calculation results agreed with experimental observations, and these results provide valuable insight into catalyst design and understanding of mechanisms of related reactions.

An in-depth theoretical study of synergistic Cu(II)/Cu(I)-mediated alkyne coupling was performed to reveal the detailed mechanism for C-C bond formation, which proceeded via an unusual dinuclear 1,2-reductive elimination. Because the reactant for dinuclear 1,2-reductive elimination was calculated to be triplet while the products were singlet, the minimum energy crossing point (MECP) was introduced to the Cu/TMEDA/alkyne system to clarify the spin crossing between triplet state and singlet state potential energy surfaces. Computational results suggest that C-H bond cleavage solely catalyzed by the Cu(I) cation is the rate-determining step of this reaction and Cu(II)-mediated dinuclear 1,2-reductive elimination after the MECP is a facile process. These conclusions are in good agreement with our previous experimental results.

Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong.

Metal-catalyzed transfer hydroformylation is an important way of cleaving C-C bonds and constructing new double bonds. The newly reported density functional theory (DFT) method, M11-L, has been used to clarify the mechanism of the rhodium-catalyzed transfer hydroformylation reported by Dong et al. DFT calculations depict a deformylation and formylation reaction pathway. The deformylation step involves an oxidative addition to the formyl C-H bond, deprotonation with a counterion, decarbonylation, and β-hydride elimination. After olefin exchange, the formylation step takes place via olefin insertion into the Rh-H bond, carbonyl insertion, and a final protonation with the conjugate acid of the counterion. Theoretical calculations indicate that the alkalinity of the counterion is important for this reaction because both deprotonation and protonation occur during the catalytic cycle. A theoretical study into the formyl acceptor shows that the driving force of the reaction is correlated with the stability of the unsaturated bond in the acceptor. Our computational results suggest that alkynes or ring-strained olefins could be used as formyl acceptors in this reaction.