Cunyuan Zhao

Key Mechanistic Features of Ni-Catalyzed C–H/C–O Biaryl Coupling of Azoles and Naphthalen-2-yl Pivalates

The mechanism of the Ni-dcype-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate was studied. Special attention was devoted to the base effect in the C-O oxidative addition and C-H activation steps as well as the C-H substrate effect in the C-H activation step. No base effect in the C(aryl)-O oxidative addition to Ni-dcype was found, but the nature of the base and C-H substrate plays a crucial role in the following C-H activation. In the absence of base, the azole C-H activation initiated by the C-O oxidative addition product Ni(dcype)(Naph)(PivO), 1B, proceeds via ΔG = 34.7 kcal/mol barrier. Addition of Cs2CO3 base to the reaction mixture forms the Ni(dcype)(Naph)[PivOCs·CsCO3], 3_Cs_clus, cluster complex rather than undergoing PivO(-) → CsCO3(-) ligand exchange. Coordination of azole to the resulting 3_Cs_clus complex forms intermediate with a weak Cs-heteroatom(azole) bond, the existence of which increases acidity of the activated C-H bond and reduces C-H activation barrier. This conclusion from computation is consistent with experiments showing that the addition of Cs2CO3 to the reaction mixture of 1B and benzoxazole increases yield of C-H/C-O coupling from 32% to 67% and makes the reaction faster by 3-fold. This emerging mechanistic knowledge was validated by further exploring base and C-H substrate effects via replacing Cs2CO3 with K2CO3 and benzoxazole (1a) with 1H-benzo[d]imidazole (1b) or quinazoline (1c). We proposed the modified catalytic cycle for the Ni(cod)(dcype)-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate.

Dinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study

Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(L(2)O)). We present a binding mode in which each terminal phosphoryl oxygen atom binds to one zinc center, respectively, and the nucleophilic 2-hydroxypropyl group coordinates to one of the zinc ions, while the hydroxide from deprotonation of a water molecule coordinates to the other zinc ion. Our calculations found a concerted mechanism for the HpPNP cleavage with a 16.5 kcal/mol reaction barrier. An alternative proposed stepwise mechanism through a pentavalent oxyphosphorane dianion reaction intermediate for the HpPNP cleavage was found to be less feasible with a significantly higher energy barrier. In this stepwise mechanism, the deprotonation of the nucleophilic 2-hydroxypropyl group is accompanied with nucleophilic attack in the rate-determining step. Calculations of the nucleophile (18)O kinetic isotope effect (KIE) and leaving (18)O KIE for the concerted mechanism are in reasonably good agreement with the experimental values. Our results indicate a specific-base catalysis mechanism takes place in which the deprotonation of the nucleophilic 2-hydroxypropyl group occurs in a pre-equilibrium step followed by a nucleophilic attack on the phosphorus center. Detailed comparison of the geometric and electronic structure for the HpPNP cleavage reaction mechanisms in the presence/absence of catalyst revealed that the catalyst significantly altered the determining-step transition state to become far more associative or tight, that is, bond formation to the nucleophile was remarkably more advanced than leaving group bond fission in the catalyzed mechanism. Our results are consistent with and provide a reliable interpretation for the experimental observations that suggest the reaction occurs by a concerted mechanism (see Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth, P.; Hengge, A. C. J. Am. Chem. Soc. 2008, 130, 17858-17866) and has a specific-base catalysis character (see Yang, M.-Y.; Iranzo, O.; Richard, J. P.; Morrow, J. R. J. Am. Chem. Soc. 2005, 127, 1064-1065).

Mechanistic Investigation of Dirhodium-Catalyzed Intramolecular Allylic C–H Amination versus Alkene Aziridination

The reaction mechanisms and chemoselectivity on the intramolecular allylic C-H amination versus alkene aziridination of 4-pentenylsulfamate promoted by four elaborately selected dirhodium paddlewheel complexes are investigated by a DFT approach. A predominant singlet concerted, highly asynchronous pathway and an alternative triplet stepwise pathway are obtained in either C-H amination or alkene aziridination reactions when mediated by weak electron-donating catalysts. A singlet stepwise C-H amination pathway is obtained under strongly donating catalysts. The rate-determining step in the C-H amination is the H-abstraction process. The subsequent diradical-rebound C-N formation in the triplet pathway or the combination of the allylic carbocation and the negative changed N center in the singlet pathway require an identical energy barrier. A mixed singlet-triplet pathway is preferred in either the C-H insertion or alkene aziridination in the Rh2(NCH3CHO)4 entry that the triplet pathway is initially favorable in the rate-determining steps, and the resultant triplet intermediates would convert to a singlet reaction coordinate. The nature of C-H amination or alkene aziridination is estimated to be a stepwise process. The theoretical observations presented in the paper are consistent with the experimental results and, more importantly, provide a thorough understanding of the nature of the reaction mechanisms and the minimum-energy crossing points.

Mechanism and Enantioselectivity of Dirhodium-Catalyzed Intramolecular C–H Amination of Sulfamate

The mechanisms and enantioselectivities of the dirhodium (Rh2L4, L = formate, N-methylformamide, S-nap)-catalyzed intramolecular C-H aminations of 3-phenylpropylsulfamate ester have been investigated in detail with BPW91 density functional theory computations. The reactions catalyzed by the Rh2(II,II) catalysts start from the oxidation of the Rh2(II,II) dimer to a triplet mixed-valent Rh2(II,III)-nitrene radical, which should facilitate radical H-atom abstraction. However, in the Rh2(formate)4-promoted reaction, as a result of a minimum-energy crossing point (MECP) between the singlet and triplet profiles, a direct C-H bond insertion is postulated. The Rh2(N-methylformamide)4 reaction exhibits quite different mechanistic characteristics, taking place via a two-step process involving (i) intramolecular H-abstraction on the triplet profile to generate a diradical intermediate and (ii) C-N formation by intersystem crossing from the triplet state to the open-shell singlet state. The stepwise mechanism was found to hold also in the reaction of 3-phenylpropylsulfamate ester catalyzed by Rh2(S-nap)4. Furthermore, the diradical intermediate also constitutes the starting point for competition steps involving enantioselectivity, which is determined by the C-N formation open-shell singlet transition state. This mechanistic proposal is supported by the calculated enantiomeric excess (94.2% ee) with the absolute stereochemistry of the product as R, in good agreement with the experimental results (92.0% ee).

DFT Study of Acceptorless Alcohol Dehydrogenation Mediated by Ruthenium Pincer Complexes: Ligand Tautomerization Governing Metal Ligand Cooperation

Metal ligand cooperation (MLC) catalysis is a popular strategy to design highly efficient transition metal catalysts. In this presented theoretical study, we describe the key governing factor in the MLC mechanism, with the Szymczaks NNN-Ru and the Milsteins PNN-Ru complexes as two representative catalysts. Both the outer-sphere and inner-sphere mechanisms were investigated and compared. Our calculated result indicates that the PNN-Ru pincer catalyst will be restored to aromatic state during the catalytic cycle, which can be considered as the driving force to promote the MLC process. On the contrary, for the NNN-Ru catalyst, the MLC mechanism leads to an unfavored tautomerization in the pincer ligand, which explains the failure of the MLC mechanism in this system. Therefore, the strength of the driving force provided by the pincer ligand actually represents a prerequisite factor for MLC. Spectator ligands such as CO, PPh3, and hydride are important to ensure the catalyst follow a certain mechanism as well. We also evaluate the driving force of various bifunctional ligands by computational methods. Some proposed pincer ligands may have the potential to be the new pincer catalysts candidates. The presented study is expected to offer new insights for MLC catalysis and provide useful guideline for future catalyst design.

DFT investigation of Ni-doped graphene: catalytic ability to CO oxidation

Herein, CO oxidation on Ni-doped graphene (Ni-Gr) is investigated by first-principle calculations. The strong binding energy (−7.57 eV) of the Ni atom at a single vacancy in graphene and high energy barrier (3.41 eV) for Ni atom mobility in graphene suggest that graphene is stable even after Ni doping, which avoids the problem of metal clustering. The stronger binding interaction between Ni-Gr and O2 than that between Ni-Gr and CO can prevent CO poisoning to Ni-Gr. To explore the catalytic effect of CO oxidation on Ni-Gr, both the Eley–Rideal (ER) and Langmuir–Hinshelwood (LH) mechanisms are investigated. The overall energy barrier at 0 K for the LH and ER mechanisms is 0.63 and 0.77 eV, respectively. At 298.15 K, the overall energy barrier for the LH mechanism decreases to 0.58 eV, whereas that for the ER mechanism increases to 0.88 eV, which implies that CO oxidation on Ni-Gr prefers to proceed via the LH mechanism kinetically. Our results show that the studied system, Ni-Gr, has chemical stability against metal clustering and CO poisoning, and it is a promising catalyst for CO oxidation at mild temperatures. This study provides a good theoretical guideline for the development of Ni-Gr based CO oxidation catalysts.

Mechanismic Investigation on the Cleavage of Phosphate Monoester Catalyzed by Unsymmetrical Macrocyclic Dinuclear Complexes: The Selection of Metal Centers and the Intrinsic Flexibility of the Ligand

The hydrolysis mechanisms of phosphor-monoester monoanions NPP(-) (p-nitrophenyl phosphate) catalyzed by unsymmetrical bivalent dinuclear complexes are explored using DFT calculations in this report. Four basic catalyst-substrate binding modes are proposed, and two optional compartments for the location of the nucleophile-coordinated metal center are also considered. Five plausible mechanisms are examined in this computational study. Mechanisms 1, 2, and 3 employ an unsymmetrical dizinc complex. All three mechanisms are based on concerted SN2 addition-substitution pathways. Mechanism 1, which involves more electronegative oxygen atoms attached to the imine nitrogen atoms in the nucleophile-coordinated compartment, was found to be more competitive compared to the other two mechanisms. Mechanisms 4 and 5 are based on consideration of the substitution of the bivalent metal centers and the intrinsic flexibility of the ligand. Both mechanisms 4 and 5 are based on stepwise SN2-type reactions. Magnesium ions with hard base properties and more available coordination sites were found to be good candidates as a substitute in the M(II) dinuclear phosphatases. The reaction energy barriers for the more distorted complexes are lower than those of the less distorted complexes. The proper intermediate distance and a functional second coordination sphere lead to significant catalytic power in the reactions studied. More importantly, the mechanistic differences between the concerted and the stepwise pathways suggest that a better nucleophile with more available coordination sites (from either the metal centers or a functional second coordination sphere) favors concerted mechanisms for the reactions of interest. The results reported in the paper are consistent with and provide a reasonable interpretation for experimental observations in the literature. More importantly, our present results provide some practical suggestions for the selection of the metal centers and how to approach the design of a catalyst.

Aquation and dimerization of osmium(II) anticancer complexes: a density functional theory study

In this paper, the hydrolytic and aqueous solution chemistry of two half-sandwich OsII arene complexes [(η6-p-cym)Os(pic)Cl] (1) and [(η6-p-cym)Os(mal)Cl] (2) (pic = 2-picolinic acid and mal = maltolate) have been investigated using density functional theory (DFT). For aquation (substitution of chloride by H2O) of the complexes, three attacking models were explored, including two forms of side attack (A and B) and back attack C. Side attack A required the lowest free energy of activation of the three, both in the gas phase and in aqueous solution, suggesting that it best describes the hydrolysis of the complexes. Both the activation and reaction energies indicated faster aquation for 2 than 1, which was in accordance with previous experimental observations. With the side attack model of the complexes, it was found that the conformations of complexes had little effect on the aquation process. Moreover, mechanistic pathways have been obtained for the dimerization of aqua adducts. As for 1a, the ligand departure was the rate-determining step with an activation free energy of 26.1 kcal mol−1, while for 2a, the first step of ring opening and protonation is rate-determining with a free energy of activation of 24.8 kcal mol−1, suggesting that 1a was kinetically more stable toward dimerization. There were three factors presented to explain the stability of 1a: differences in HOMO/LUMO densities, the large activation energy of 1a, and stabilization of Os-pic bonding. This study assists in understanding the aqueous solution chemistry of the anticancer complexes and in the design of novel anticancer drugs.

Removal of NO with silicene: a DFT investigation

Removing or reducing NO is meaningful for environment protection. Herein, the investigation of the probability of NO reduction on silicene is presented utilizing DFT calculations. Two mechanisms for NO reduction on silicene are provided: a direct dissociation mechanism and a dimer mechanism. The direct dissociation mechanism is characterized as the direct breaking of the N–O bond. The calculated potential energy surfaces show that the total energy barrier in the favored direct dissociation pathway is 0.466 eV. On the other hand, the dimer mechanism is identified to undergo a (NO)2 dimer formation on silicene, which then decomposes into N2O + Oad or N2 + 2Oad. The (NO)2 dimer formation on silicene is found to be feasible both in thermodynamics and kinetics. The formation energy barriers for (NO)2 dimer are lower than 0.231 eV. The calculation results indicate that the (NO)2 dimers can be readily reduced into N2O or N2. The energy barriers in the favored decomposition pathways to produce N2O are quite low (<0.032 eV). The energy barrier for the release of N2 is calculated to be 0.156 eV. The further reduction of N2O to N2 on silicene is also investigated. The results indicate it is easy to reduce N2O to N2 with an energy barrier of only 0.445 eV. NO reduction on silicene hence prefers to generate N2 via the dimer mechanism when compared to the direct dissociation. NO reduction on silicene with silicane as substrate is further proved to proceed via the same reduction mechanism as compared with the free-standing model. Hence, our results presented here suggest that silicene can be a potential material in NO removal, which will reduce NO into environmentally-friendly gases.

Density functional theory study of the mechanism of zinc carbenoid promoted cyclopropanation of allenamides

The mono- and bis-cyclopropanation of allenamides with the zinc carbenoid Zn(CH2Cl)2 have been studied using density functional theory calculations employing the M06 functional. The monomeric and dimeric precursor complexes were both constructed to model the reaction processes. In the monomeric reaction, the formation of the endo-monocyclopropyl species takes place via a methylene transfer pathway rather than a carbometalation pathway. The formation of the exo-monocyclopropyl species does not readily occur via a methylene transfer pathway due to a high activation barrier. The corresponding carbometalation pathway was not able to be found. Following the monocyclopropanation step, the biscyclopropanation of the endo-monocyclopropyl species is facile to form amidospiro[2.2]pentane. In the aggregation model, the allenamides and the zinc carbenoid form a dimer aggregate that is then followed by two pathways. One pathway takes place via transition states inside the aggregate structure (denoted here as a closed-mode process) while the other pathway introduces another zinc carbenoid molecule from outside the aggregation species (denoted here as an open-mode process). The aggregate mechanisms are not favored because the dimeric reactant of the open-mode process is not stable to coexist with the monomer and the activation barriers of the two aggregate pathways are higher than those of the monomeric pathways. The calculation results show that the key factors in the reaction mechanisms are the co-planarity of the allenic moiety with the oxazolidinone ring, the torsional strain in the butterfly-type transition state, the ring strain in the substrate–carbenoid complexes and the coordination between the carbenoid-Zn and O(CO) atoms and other long-distance interactions.