Key Role of Pd^IV Intermediates in Promoting Pd^II-Catalyzed Dehydrogenative Homocoupling of Two Arenes: A DFT Study

Palladium-catalyzed dehydrogenative homocoupling of two arenes provides a powerful and straightforward method for the synthesis of biaryls. In contrast to the Heck reaction for efficient cross-coupling of arene with alkene, dehydrogenative homocoupling of two arenes is not readily accessible through traditional Pd^II/0/II catalytic cycles, which limits its application to the construction of desired C–C bonds. Herein, we performed DFT studies to explore the detailed mechanisms of the Pd^II-catalyzed homocoupling of benzophenones in the presence of the strong oxidant K₂S₂O₈. Calculation results demonstrated that the favorable reaction pathway is a Pd^II/IV/II catalytic cycle, including four sequential processes: C–H activation at the Pd^II center, oxidation of Pd^II to Pd^IV, C–H activation at the Pd^IV center, and reductive elimination. It was found that C–H activation at the Pd^IV center is the rate-determining process, with a free energy barrier of 26.0 kcal mol^–1. The oxidant K₂S₂O₈ plays an important role in converting Pd^II to Pd^IV and facilitating the second C–H activation step. In contrast, the alternative Pd^II/0/II pathway has been characterized as an inaccessible reaction channel from our calculations, because the second C–H activation is hindered by a free energy barrier of 38.9 kcal mol^–1. In addition, the electronic effect of the spectator ligand on C–H activation has been investigated in terms of molecular orbital theory, which disclosed the origin of the critical role of Pd^IV intermediates in promoting the biaryl synthesis

Key Role of Pd^IV Intermediates in Promoting Pd^II-Catalyzed Dehydrogenative Homocoupling of Two Arenes: A DFT Study

Palladium-catalyzed dehydrogenative homocoupling of two arenes provides a powerful and straightforward method for the synthesis of biaryls. In contrast to the Heck reaction for efficient cross-coupling of arene with alkene, dehydrogenative homocoupling of two arenes is not readily accessible through traditional Pd^II/0/II catalytic cycles, which limits its application to the construction of desired C–C bonds. Herein, we performed DFT studies to explore the detailed mechanisms of the Pd^II-catalyzed homocoupling of benzophenones in the presence of the strong oxidant K₂S₂O₈. Calculation results demonstrated that the favorable reaction pathway is a Pd^II/IV/II catalytic cycle, including four sequential processes: C–H activation at the Pd^II center, oxidation of Pd^II to Pd^IV, C–H activation at the Pd^IV center, and reductive elimination. It was found that C–H activation at the Pd^IV center is the rate-determining process, with a free energy barrier of 26.0 kcal mol^–1. The oxidant K₂S₂O₈ plays an important role in converting Pd^II to Pd^IV and facilitating the second C–H activation step. In contrast, the alternative Pd^II/0/II pathway has been characterized as an inaccessible reaction channel from our calculations, because the second C–H activation is hindered by a free energy barrier of 38.9 kcal mol^–1. In addition, the electronic effect of the spectator ligand on C–H activation has been investigated in terms of molecular orbital theory, which disclosed the origin of the critical role of Pd^IV intermediates in promoting the biaryl synthesis

An Explicit Interpretation of the Directing Group Effect for the Pd(OAc)₂‑Catalyzed Aromatic C–H Activations

A comprehensive DFT investigation has been performed for a series of the Pd­(OAc)₂-catalyzed C–H activations, updating and extending the understanding of directing group effect. In the beginning, the directed and undirected C–H activation mechanisms, based on 10 model reactions, have been discussed comparatively, which disclosed that directing group can exert a thermodynamic driving force, not necessarily a kinetic promotion, on the C–H activation process. Formation of the open palladation species via the undirected pathway is thermodynamically unspontaneous (Δ<i>G</i> = 4–9 kcal/mol), in sharp contrast to that of the cyclopalladation species via the directed pathway (Δ<i>G</i> < 0). Further calculations revealed that the free-energy barriers of proton-transfer are in fact not so high on the undirected pathway (17–24 kcal/mol), while mediation of some O-center groups in the directed pathway would increase the free-energy barriers of proton-transfer. For pyridine <i>N</i>-oxide systems, the undirected mechanism was estimated to be more plausible than the 4-member-directed one both thermodynamically and kinetically. In addition, the uncommon 7-membered cyclopalladation has been tentatively explored using two current examples, predicting that electron-rich directing groups can help to stabilize the 7-membered palladacycles formed

Catalytic C–H Activation/C–C Coupling Reaction: DFT Studies on the Mechanism, Solvent Effect, and Role of Additive

A series of density functional theory (DFT) experiments, employing the B3LYP+IDSCRF/BS1 and B3LYP+IDSCRF/DZVP methods, have been carried out for the Pd­(OAc)₂-catalyzed enamide–siloxane C–H activation/C–C coupling reactions. The results reveal that there are four processes, namely C–H activation, transmetalation (TM), reductive elimination (RE), and separation of product (SP) and recycling of catalyst (RC), each of which is consist of different steps. In order to fully understand the origin of regiospecific C–H activation/C–C coupling on the alicyclic ring experimentally observed, the conformational preference, kinetic aspects, and relative stabilities of the competitive products have been explored. In addition, the roles of additive silver salt AgF and solvent dioxane have also been addressed, providing valuable details upon which to rationally optimize experimental conditions

DFT Studies on the Dirhodium-Catalyzed [3 + 2] and [3 + 3] Cycloaddition Reactions of Enol Diazoacetates with Isoquinolinium Methylide: Mechanism, Selectivity, and Ligand Effect

The reaction mechanisms of dirhodium-catalyzed [3 + 2] and [3 + 3] cycloaddition between enol diazoacetate and isoquinolinium methylide have been studied in detail using density functional theory and a solution-phase translational entropy model. The reaction starts with the formation of a metallic carbene intermediate first, from which two competing reaction channels of [3 + 2] and [3 + 3] cycloaddition take place. For <b>CAT1</b>-catalyzed reactions, the calculated activation free energy barriers for [3 + 3] and [3 + 2] cycloaddition reactions are 14.3 and 16.0 kcal mol^–1, respectively, which is in good agreement with the ratio of products. Both the steric and electronic effects have been considered for <b>CAT2</b>- and <b>CAT3</b>-catalyzed reactions, with which the ratio of products has also been rationalized

DFT Studies on the Dirhodium-Catalyzed [3 + 2] and [3 + 3] Cycloaddition Reactions of Enol Diazoacetates with Isoquinolinium Methylide: Mechanism, Selectivity, and Ligand Effect

The reaction mechanisms of dirhodium-catalyzed [3 + 2] and [3 + 3] cycloaddition between enol diazoacetate and isoquinolinium methylide have been studied in detail using density functional theory and a solution-phase translational entropy model. The reaction starts with the formation of a metallic carbene intermediate first, from which two competing reaction channels of [3 + 2] and [3 + 3] cycloaddition take place. For <b>CAT1</b>-catalyzed reactions, the calculated activation free energy barriers for [3 + 3] and [3 + 2] cycloaddition reactions are 14.3 and 16.0 kcal mol^–1, respectively, which is in good agreement with the ratio of products. Both the steric and electronic effects have been considered for <b>CAT2</b>- and <b>CAT3</b>-catalyzed reactions, with which the ratio of products has also been rationalized

DFT Study on Rhodium-Catalyzed Intermolecular [2 + 2] Cycloaddition of Terminal Alkynes with Electron-Deficient Alkenes

Density functional theory (DFT) calculations with the B3LYP functionals elucidated the reactivity, selectivity, and mechanisms of a rhodium-catalyzed intermolecular [2 + 2] cycloaddition of terminal alkynes with electron-deficient alkenes. The most plausible reaction pathway was discussed as three distinct processes in full catalytic cycles, including (1) substrate exchange, (2) nucleophilic addition and cyclization, and (3) separation of product and recycling of catalyst; the formal [2 + 2] cycloaddition indeed proceeded through a rate-determining and stepwise addition–cyclization process. We then compared the outer-sphere and inner-sphere mechanisms for the formation of cyclobutene intermediates and reported that the former pathway is more accessible kinetically and thus more competitive, being contrary to the proposed mechanism for some nickel-catalyzed cycloaddition reactions in the literature. Furthermore, the substituent effect has been investigated using various alkenes CH₂CHR (R = COOMe, CN, H, CH₃) as reaction partners, which disclosed that the reaction pathway for electron-deficient alkenes was mediated by a zwitterion intermediate, whereas that for electron-neutral alkenes was characterized as a diradical-like mechanism with an inaccessible free-energy barrier of more than 46 kcal mol^–1. In addition, the effects of ligand and base have been discussed in detail from the perspective of Houk’s distortion/interaction model, providing a valuable case study for understanding the roles played by different phosphine ligands and additives

DFT Studies on the Mechanism of Palladium(IV)-Mediated C–H Activation Reactions: Oxidant Effect and Regioselectivity

A series of density functional theory calculations have been employed to study the Pd^IV-mediated C–H activation in CD₃CN solvent. B3LYP/DZVP, B3LYP/BS1, and B3LYP-D3/DZVP were comparatively employed to locate the geometric parameters of possible stationary points, with IDSCRF radii constituting the cavity. The novel reaction mechanism provided was divided into three distinct steps: oxidation addition, ligand substitution, and C–H activation. The distinct chemical behaviors of different oxidants have been addressed with Bader’s atoms-in-molecules wave function analysis, providing a reasonable explanation for the experimental observation. Regioselectivity was dynamically controlled by the rate-determining oxidation step. At the same time, the basis set effect was also discussed for this Pd^II → Pd^IV transformation

Thorium Oxo and Sulfido Metallocenes: Synthesis, Structure, Reactivity, and Computational Studies

The synthesis, structure, and reactivity of thorium oxo and sulfido metallocenes have been comprehensively studied. Heating of an equimolar mixture of the dimethyl metallocene [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThMe₂ (<b>2</b>) and the bis-amide metallocene [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂Th(NH-<i>p</i>-tolyl)₂ (<b>3</b>) in refluxing toluene results in the base-free imido thorium metallocene, [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThN(<i>p</i>-tolyl) (<b>4</b>), which is a useful precursor for the preparation of oxo and sulfido thorium metallocenes [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThE (E = O (<b>5</b>) and S (<b>15</b>)) by cycloaddition–elimination reaction with Ph₂CE (E = O, S) or CS₂. The oxo metallocene <b>5</b> acts as a nucleophile toward alkylsilyl halides, while sulfido metallocene <b>15</b> does not. The oxo metallocene <b>5</b> and sulfido metallocene <b>15</b> undergo a [2 + 2] cycloaddition reaction with Ph₂CO, CS₂, or Ph₂CS, but they show no reactivity with alkynes. Density functional theory (DFT) studies provide insights into the subtle interplay between steric and electronic effects and rationalize the experimentally observed reactivity patterns. A comparison between Th, U, and group 4 elements shows that Th⁴⁺ behaves more like an actinide than a transition metal

Thorium Oxo and Sulfido Metallocenes: Synthesis, Structure, Reactivity, and Computational Studies

The synthesis, structure, and reactivity of thorium oxo and sulfido metallocenes have been comprehensively studied. Heating of an equimolar mixture of the dimethyl metallocene [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThMe₂ (<b>2</b>) and the bis-amide metallocene [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂Th(NH-<i>p</i>-tolyl)₂ (<b>3</b>) in refluxing toluene results in the base-free imido thorium metallocene, [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThN(<i>p</i>-tolyl) (<b>4</b>), which is a useful precursor for the preparation of oxo and sulfido thorium metallocenes [η⁵-1,2,4-(Me₃C)₃C₅H₂]₂ThE (E = O (<b>5</b>) and S (<b>15</b>)) by cycloaddition–elimination reaction with Ph₂CE (E = O, S) or CS₂. The oxo metallocene <b>5</b> acts as a nucleophile toward alkylsilyl halides, while sulfido metallocene <b>15</b> does not. The oxo metallocene <b>5</b> and sulfido metallocene <b>15</b> undergo a [2 + 2] cycloaddition reaction with Ph₂CO, CS₂, or Ph₂CS, but they show no reactivity with alkynes. Density functional theory (DFT) studies provide insights into the subtle interplay between steric and electronic effects and rationalize the experimentally observed reactivity patterns. A comparison between Th, U, and group 4 elements shows that Th⁴⁺ behaves more like an actinide than a transition metal