Computational Mechanistic Study Research Articles

Ethene hydrogenation vs. dimerization over a faujasite-supported [Rh(C2H4)2] complex. A computational study of mechanism

A DFT study allows one to understand the selectivity for ethene hydrogenation over dimerization by the well-characterized faujasite-supported [Rh(C2H4)2]+ complex.

Unveiling the role of boroxines in metal-free carbon-carbon homologations using diazo compounds and boronic acids.

By means of computational and experimental mechanistic studies the fundamental role of boroxines in the reaction between diazo compounds and boronic acids was elucidated. Consequently, a selective metal-free carbon-carbon homologation of aryl and vinyl boroxines using TMSCHN2, giving access to TMS-pinacol boronic ester products, was developed.

Computational Mechanistic Study of Redox-Neutral Rh(III)-Catalyzed C-H Activation Reactions of Arylnitrones with Alkynes: Role of Noncovalent Interactions in Controlling Selectivity.

The mechanism of redox-neutral Rh(III)-catalyzed coupling reactions of arylnitrones with alkynes was investigated by density functional theory (DFT) calculations. The free energy profiles associated with the catalytic cycle, involving C(sp2)-H activation, insertion of alkyne, transfer of O atom, cyclization and protodemetalation, are presented and analyzed. An overwhelming preference for alkyne insertion into Rh-C over Rh-O is observed among all pathways, and the most favorable route is determined. The pivalate-assisted C-H activation step is turnover-limiting, and the cyclization step determines the diastereoselectivity of the reaction, with the stereoselectivity arising mainly from the difference of noncovalent interactions in key transition states. The detailed mechanism of O atom transfer, RhIII-RhI-RhIII versus RhIII-RhV-RhIII cycle, is discussed.

A computational mechanistic study of the deamination reaction of melamine

A detailed computational study of the deamination reaction of melamine by OH–, nH2O/OH–, nH2O (where n = 1, 2, 3), and protonated melamine with H2O, has been carried out using density functional theory and ab initio calculations. All structures were optimized at M06/6-31G(d) level of theory, as well as with the B3LYP functional with each of the basis sets: 6-31G(d), 6-31 + G(d), 6-31G(2df,p), and 6-311++G(3df,3pd). B3LYP, M06, and ωB97XD calculations with 6-31 + G(d,p) have also been performed. All structures were optimized at B3LYP/6-31 + G(d,p) level of theory for deamination simulations in an aqueous medium, using both the polarizable continuum solvation model and the solvation model based on solute electron density. Composite method calculations have been conducted at G4MP2 and CBS-QB3. Fifteen different mechanistic pathways were explored. Most pathways consisted of two key steps: formation of a tetrahedral intermediate and in the final step, an intermediate that dissociates to products via a 1,3-proton shift. The lowest overall activation energy, 111 kJ mol−1 at G4MP2, was obtained for the deamination of melamine with 3H2O/OH−.

Synergistic Heterobimetallic Manifold for Expedient Manganese(I)-Catalyzed C-H Cyanation.

The manganese-catalyzed cyanation of inert C-H bonds was achieved within a heterobimetallic catalysis regime. The manganese(I) catalysis proved widely applicable and enabled C-H cyanations on indoles, pyrroles and thiophenes by facile C-H manganesation. The robustness of the manganese catalyst set the stage for the racemization-free C-H cyanation of amino acids with excellent levels of positional and chemo selectivity by the new cyanating agent NCFS. Experimental and computational mechanistic studies provided strong support for a synergistic heterobimetallic activation mode, facilitating the key C-C formation.

Rh(III)-Catalyzed Cascade Oxidative Annulation of Benzoylacetonitrile with Alkynes: Computational Study of Mechanism, Reactivity, and Regioselectivity.

The mechanism of the rhodium-catalyzed cascade oxidative annulation of benzoylacetonitrile with alkynes is investigated using density functional theory calculations. The result shows that the reaction undergoes a stepwise annulation process, wherein the 1-naphthol acts as an intermediate. The first-step annulation involves the sp(3) C-H bond cleavage, sp(2) C-H bond cleavage, alkyne insertion into the Rh-C(sp(2)) bond, ketone enolization, and reductive elimination to produce the 1-naphthol intermediate. The second-step annulation involves the O-H cleavage, sp(2) C-H bond cleavage, alkyne insertion into the Rh-C(sp(2)) bond, and C-O reductive elimination to generate the final product naphtho[1,8-bc]-pyran. The sp(3) C-H bond cleavage rather than the sp(2) C-H bond cleavage is found to be the rate-determining step of the catalytic cycle. The ketone enolization should occur before the reductive elimination. The substituent effects on the reactivities and regioselectivities of reactions are also analyzed. These calculation results shed light on some ambiguous suggestions from experiments.

Computational Mechanistic Study of Thionation of Carbonyl Compounds with Lawesson's Reagent.

The thionation reaction of carbonyl compounds with Lawesson's reagent (LR) has been studied using density functional theory methods and topological analyses. After dissociation of LR, the reaction takes place through a two-step mechanism involving (i) a concerted cycloaddition between one monomer and the carbonyl compound to form a four-membered intermediate and (ii) a cycloreversion leading to the thiocarbonyl derivative and phenyl(thioxo)phosphine oxide. Topological analyses confirmed the concertedness and asynchronicity of the process. The second step is the rate-limiting one, and the whole process resembles the currently accepted mechanism for the lithium salt-free Wittig reaction. No zwitterionic intermediates are formed during the reaction, although stabilizing electrostatic interactions are present in initial stages. Phenyl(thioxo)phosphine oxide formed in the thionation reaction is capable of performing a second thionation, although with energy barriers higher than the first one. The driving force of the thionation reactions is the formation of trimers from the resulting monomers. In agreement with experimental observations, the amides are the most reactive when compared with esters, aldehydes, and ketones and the reaction is slightly influenced by the polarity of the solvent. Whereas for amides and esters substituents have little effect, aldehydes and ketones are influenced by both steric and electronic effects.

Azomethine Ylides from Nitrones: Using Catalytic nBuLi for the Totally Stereoselective Synthesis of trans-2-Alkyl-3-oxazolines.

The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways.

N-Alkylation by Hydrogen Autotransfer Reactions [corrected

Owing to the importance of amine/amide derivatives in all fields of chemistry, and also the green and environmentally benign features of using alcohols as alkylating reagents, the relatively high atom economic dehydrative N-alkylation reactions of amines/amides with alcohols through hydrogen autotransfer processes have received much attention and have developed rapidly in recent decades. Various efficient homogeneous and heterogeneous transition metal catalysts, nano materials, electrochemical methods, biomimetic methods, asymmetric N-alkylation reactions, aerobic oxidative methods, and even certain transition metal-free, catalyst-free, or autocatalyzed methods, have also been developed in recent years. With a brief introduction to the background and developments in this area of research, this chapter focuses mainly on recent progress and technical and conceptual advances contributing to the development of this research in the last decade. In addition to mainstream research on homogeneous and heterogeneous transition metal-catalyzed reactions, possible mechanistic routes for hydrogen transfer and alcohol activation, which are key processes in N-alkylation reactions but seldom discussed in the past, the recent reports on computational mechanistic studies of the N-alkylation reactions, and the newly emerged N-alkylation methods based on novel alcohol activation protocols such as air-promoted reactions and transition metal-free methods, are also reviewed in this chapter. Problems and bottlenecks that remained to be solved in the field, and promising new research that deserves greater future attention and effort, are also reviewed and discussed.

Gas-phase synthesis of 3-carboethoxy-quinolin-4-ones. A comprehensive computational mechanistic study to uncover the dark side of the Gould–Jacobs reaction

A set of 3-carboethoxy-quinolin-4-ones were synthesized from diethyl 2-((arylamino)methylene) malonates through a Gould–Jacobs cyclization using flash vacuum pyrolysis (FVP). A detailed mechanistic study was done using DFT and Coupled Clusters models.

Experimental and Computational Mechanistic Studies Guiding the Rational Design of Molecular Electrocatalysts for Production and Oxidation of Hydrogen

Understanding how to control the movement of protons and electrons is crucial to the design of fast, efficient electrocatalysts for H2 production and oxidation based on earth-abundant metals. Our work seeks to address fundamental questions about proton movement. We have demonstrated that incorporating a pendant amine functioning as a proton relay in the second coordination sphere of a metal complex helps proton mobility, resulting in faster and more energy-efficient catalysts. Proton-transfer reactions can be rate-limiting and are influenced by several factors, such as pKa values, steric effects, hydrogen bonding, and solvation/desolvation of the exogenous base and acid employed. The presence of multiple protonation sites introduces branching points along the catalytic cycle, making less productive pathways accessible or leading to the formation of stable off-cycle species. Using ligands with only one pendant amine mitigates this problem and results in catalysts with high rates for production of H2, although generally at higher overpotentials. For H2 oxidation catalysts, iron complexes with a high H2 binding affinity were developed. However, these iron complexes had a pKa mismatch between the protonated metal center and the protonated pendant amine, and consequently intramolecular proton movement was slow. Taken altogether, our results demonstrate the necessity of optimizing the entire catalytic cycle because optimization of a specific catalytic step can negatively influence another step and not necessarily lead to a better catalytic performance. We discuss a general procedure, based on thermodynamic arguments, which allows the simultaneous minimization of the free-energy change of each catalytic step, yielding a nearly flat free-energy surface, with no large barriers due to energy mismatches from either high- or low-energy intermediates.

Computational Mechanistic Study of the Hydrogenation and Dehydrogenation Reactions Catalyzed by Cobalt Pincer Complexes

The mechanisms of hydrogenation and dehydrogenation reactions catalyzed by a series of aliphatic PNP cobalt pincer complexes, [(PNRPiPr)CoH]+ (R = H and CH2X; X = H, Me, NH2, OMe, OH, F, and Cl) and [(PNPiPr)CoH], are studied by density functional theory calculations. In the hydrogenation of propylene catalyzed by [(PNRPiPr)CoH]+, a propylene molecule first inserts into the Co–H bond to form a Co–C bond. Then a H2 molecule is inserted into the Co–C bond for the formation and release of propane. The influence of different substituents on the N atom of the pincer ligand for the hydrogenation process is investigated. The relations between the field/inductive effect (σF) and total free energy barriers and the properties of the lowest energy intermediates, including the Co–N bond lengths, the lowest unoccupied molecular orbital energies, and the Wiberg bond indices of Co–N bonds, are analyzed. The results show that σF plays a crucial role in the substituent effect. The mechanism of acceptorless dehydrogenation...

Computational Mechanism Study of Catalyst-Dependent Competitive 1,2-C→C, −O→C, and −N→C Migrations from β-Methylene-β-silyloxy-β-amido-α-diazoacetate: Insight into the Origins of Chemoselectivity

Doyle et al. [J. Am. Chem. Soc. 2013, 135, 1244−1247] recently reported an efficient catalyst-controlled chemoselectivity of competitive 1,2-C→C, −O→C, and −N→C migrations from β-methylene-β-silyloxy-β-amido-α-diazoacetates using dirhodium or copper catalysts. With the aid of density functional theory calculations, the present study systematically probed the mechanism of the aforementioned reactions and the origins of the catalyst-controlled chemoselectivity. Similar to the method reported in the literature, simplified catalyst models Rh2(O2CH)4 and Rh2(N-methylformamide)4 have been used in our initial calculations. However, using the Rh2(O2CH)4 model could not describe the energies of all possible pathways, and high selectivity of three competitive migrations could not be achieved. In order to appropriately describe this 1,2-migration system, real catalyst models Rh2(cap)4, Rh2(esp)2, and CuPF6 have been employed. It was found that the steric and electronic effects of ligands significantly influence the free energy barrier, which ultimately changes the chemoselectivity. In the CuPF6 system, the electronic effects, coupled with the steric factor, give a qualitative explanation for the exclusive chemoselectivity of 1,2-N→C migration over 1,2-C→C or −O→C migration. On the other hand, the bulky ligands of dirhodium catalysts result in the significant steric hindrance around the dirhodium centers and withdrawal of the empty space around the bulky −OTBS group. By analyzing the divergence of three different migration transition states using the distortion/interaction and natural bond orbital analyses, it was found that the 1,2-N→C migration will suffer from a high free energy barrier because of the steric repulsion between the carbonyl group and the carbonyl oxygen of the pyrazolidinone ring. For 1,2-C→C and −O→C migrations, changing the ligands of dirhodium catalysts can change the electronic properties of carbenes, and that is the reason for controlling the major product by changing the dirhodium catalysts. The mechanistic proposal is supported by the calculated chemoselectivities, which are in good agreement with the experimental results.

Palladium-Catalyzed Ring Expansion of Spirocyclopropanes to Form Caprolactams and Azepanes

A palladium(0)-catalyzed rearrangement of piperidones and piperidines bearing a spirocyclopropane ring was developed. The ring expansion reaction led to a variety of functionalized caprolactam and azepane products in good to excellent yields. Experimental and computational mechanistic studies revealed an initial oxidative addition of the distal carbon-carbon bond of a cyclopropane ring to the palladium(0) catalyst and the relief of ring strain as a driving force for product formation.

Simple boron removal from seawater by using polyols as complexing agents: A computational mechanistic study

The complexation of boric acid (B(OH)3), the primary form of aqueous boron at moderate pH, with polyols is proposed and mechanistically studied as an efficient way to improve membrane processes such as reverse osmosis (RO) for removing boron in seawater by increasing the size of aqueous boron compounds. Computational chemistry based on the density functional theory (DFT) was used to manifest the reaction pathways of the complexation of B(OH)3 with various polyols such as glycerol, xylitol, and mannitol. The reaction energies were calculated as −80.6, −98.1, and −87.2 kcal/mol for glycerol, xylitol, and mannitol, respectively, indicating that xylitol is the most thermodynamically favorable for the complexation with B(OH)3. Moreover, the 1: 2 molar ratio of B(OH)3 to polyol was found to be more favorable than the ratio of 1: 1 for the complexation. Meanwhile, latest lab-scale actual RO experiments successfully supported our computational prediction that 2 moles of xylitol are the most effective as the complexing agent for 1 mole of B(OH)3 in aqueous solution.

Computational mechanistic study of the Julia-Kocieński reaction.

This paper describes the first detailed computational mechanistic study of the Julia-Kocieński olefination between acetaldehyde (1) and ethyl 1-phenyl-1H-tetrazol-5-yl sulfone (2), considered a paradigmatic example of the reaction between unsubstituted alkyl PT sulfones and linear aliphatic aldehydes. The theoretical study was performed within the density functional approach through calculations at the B3LYP/6-311+G(d,p) level for all atoms except sulfur for which the 6-311+G(2df,p) basis set was used. All the different intermediates and transition states encountered along the reaction pathways leading to final E and Z olefins have been located and the relative energies calculated, both for the reactions with potassium- and lithium-metalated sulfones, in THF and toluene, respectively. We have essentially confirmed the complex multistep mechanistic manifold proposed by others; however, the formation of a spirocyclic intermediate in the Smiles rearrangement was excluded. Instead, we found that this step involves a concerted, though asynchronous, mechanism. Moreover, our calculations nicely fit with the diastereoselectivities observed experimentally for potassium- and lithium-metalated sulfones, in THF and toluene, respectively.

Computational Mechanistic Studies on Reactions of Transition Metal Complexes with Noninnocent Pincer Ligands: Aromatization–Dearomatization or Not

The development of green chemistry has attracted chemists’ attentions in recent years. Among them, Milstein and co-workers have discovered a new mode of metal–ligand cooperation in complexes in which an aromatization–dearomatization process of the pyridine- or acridine-based PNP and PNN “pincer” ligands appears to be a key element. These complexes were reported to lead to unusual X–H (X = H, C, O, N, and B) activation reactions and to environmentally benign catalysis involving dehydrogenative coupling reactions and hydrogenation reactions, representing an important development in green chemistry. This review provides a summary of theoretical studies on the mechanisms of the reactions mediated by transition metal complexes with noninnocent pincer ligands synthesized by Milstein and co-workers. The aromatization–dearomatization process of the pyridine- or acridine-based PNP and PNN “pincer” ligands were found to play important roles in some reactions, while other reactions do not involve the aromatization–d...

Mechanism of Si Island Formation in SAPO-34

With the aim of understanding the Si island formation in SAPO-34, we have carried out a computational mechanistic study. Briefly, the Si island formation in SAPO-34 is explained by three successive reactions. First, the framework Si atom is removed from the framework through the action of four water molecules. Second, the hydrogarnet defect generated by the desilication is healed by an available H3PO4 molecule. Third, the extra framework Si(OH)4 species inserts in the framework position of a phosphorus atom while, in a concerted fashion, “kicking out” the phosphorus atom as a H3PO4 extra-framework species. When these exchanges of framework and extra-framework species are repeated, the isolated Si atoms may eventually cluster into Si islands.

Computational Mechanistic Study of Fe-Catalyzed Hydrogenation of Esters to Alcohols: Improving Catalysis by Accelerating Precatalyst Activation with a Lewis Base

DFT calculations have been performed to gain mechanistic insight into ester hydrogenation to alcohols (exemplified by PhCO2CH3 +2H2 → PhCH2OH + CH3OH), catalyzed by a well-defined Fe-PNP pincer hydridoborohydride complex (1). The entire catalytic process includes precatalyst activation to an active species trans-dihydride complex 2, 2-catalyzed transformation of PhCO2CH3 + H2 → PhCHO + CH3OH, hydrogenation of PhCHO to PhCH2OH, and catalyst regeneration via H2 addition to the dehydrogenated 2 (i.e., complex 5). The transformation, PhCO2CH3 + H2 → PhCHO + CH3OH, proceeds via hydrogenation of PhCO2CH3 to a hemiacetal PhCH(OH)(OCH3), followed by decomposition of the hemiacetal to methanol and benzaldehyde. The Fe-complex 5 was found to be capable of facilitating the decomposition of the hemiacetal. The ineffectiveness of the catalytic system in hydrogenating methyl salicylate is attributed to the intrinsically lower reactivity of the ester toward C═O reduction and a very facile side-reaction, which is adding the phenol OH group of the hemiacetal intermediate stemmed from methyl salicylate to the Fe–N active site of 5. Computations of various catalyst initiation pathways show that the initiation without the aid of an additive is very unfavorable, thus we suggest the use of a Lewis base such as NR3 (R = Me and Et) and PR3 (R = nBu and tBu) to accelerate precatalyst (1) activation, because a Lewis base could form a stable adduct (BH3–NR3/PR3) with the BH3 moiety of 1. In agreement with greatly enhanced kinetics and thermodynamics of the initiation process suggested by the DFT calculations, experimental study shows that the addition of a catalytic amount of NEt3 doubled the yield of benzyl alcohol from the hydrogenation of methyl benzoate, when compared to the case without using any additive. The trans effect of the hydride on the reactivity of 2 and steric effect of the pincer substituents on the stability of 2 are also discussed.

Computational Mechanistic Study of the Gas Phase Oxidation of Methanol with Ozone

The reaction of methanol and ozone on the singlet potential energy surface has been carried out using the RMP2 theoretical approach in connection with the 6–311++G(d, p) basis set. To obtain a more reliable energy, single point calculations were performed for all species at the CCSD(T) level. One pre-reactive complex C1 is formed between the reactants. From a variety of the complexes, five types of product are obtained, of which four types have enough thermodynamic stability at the RMP2 level. In the thermodynamic approach, the most favoured route begins with the formation of a pre-reactive complex C1 and gives H2CO+H2O+3O2 as the final adducts. This process is exothermic by – 73.243 kcal mol–1 in standard enthalpy and exergonic by – 83.382 kcal mol–1.