DFT Study of the Molybdenum‐Catalyzed Deoxydehydration of Vicinal Diols

The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an Mo^VI oxo complex, oxidative cleavage of the diol resulting in an Mo^IV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations.     

Mechanistic Study on Oxorhenium‐Catalyzed Deoxydehydration and Allylic Alcohol Isomerization

The reaction mechanism of 1,2×n‐deoxydehydration (DODH; n=1, 2, 3 …) reactions with 1‐butanol as a reductant in the presence of methyltrioxorhenium(VII) catalyst has been investigated by DFT. The reduced rhenium compound, methyloxodihydroxyrhenium(V), serves as the catalytically relevant species in both allylic alcohol isomerization and subsequent DODH processes. Compared with three‐step pathway A, involving [1,3]‐transposition of allylic alcohols, direct two‐step pathway B is an alternative option with lower activation barriers. The rate‐limiting step of the DODH reaction is the first hydrogen transfer in methyltrioxorhenium(VII) reduction. Moreover, the increase in the distance between two hydroxyl groups in direct 1,2×n‐DODH reactions for C4 and C6 diols results in a higher barrier height.     

Highly Efficient Chemical Process To Convert Mucic Acid into Adipic Acid and DFT Studies of the Mechanism of the Rhenium‐Catalyzed Deoxydehydration

The production of bulk chemicals and fuels from renewable bio‐based feedstocks is of significant importance for the sustainability of human society. Adipic acid, as one of the most‐demanded drop‐in chemicals from a bioresource, is used primarily for the large‐volume production of nylon‐6,6 polyamide. It is highly desirable to develop sustainable and environmentally friendly processes for the production of adipic acid from renewable feedstocks. However, currently there is no suitable bio‐adipic acid synthesis process. Demonstrated herein is the highly efficient synthetic protocol for the conversion of mucic acid into adipic acid through the oxorhenium‐complex‐catalyzed deoxydehydration (DODH) reaction and subsequent Pt/C‐catalyzed transfer hydrogenation. Quantitative yields (99 %) were achieved for the conversion of mucic acid into muconic acid and adipic acid either in separate sequences or in a one‐step process.     

On the Mechanism of Bifunctional Squaramide‐Catalyzed Organocatalytic Michael Addition: A Protonated Catalyst as an Oxyanion Hole

A joint experimental–theoretical study of a bifunctional squaramide‐amine‐catalyzed Michael addition reaction between 1,3‐dioxo nucleophiles and nitrostyrene has been undertaken to gain insight into the nature of bifunctional organocatalytic activation. For this highly stereoselective reaction, three previously proposed mechanistic scenarios for the critical C?C bond‐formation step were examined. Accordingly, the formation of the major stereoisomeric products is most plausible by one of the bifunctional pathways that involve electrophile activation by the protonated amine group of the catalyst. However, some of the minor product isomers are also accessible through alternative reaction routes. Structural analysis of transition states points to the structural invariance of certain fragments of the transition state, such as the protonated catalyst and the anionic fragment of approaching reactants. Our topological analysis provides deeper insight and a more general understanding of bifunctional noncovalent organocatalysis.     

A DFT Study on the Mechanism of Rh2II,II‐Catalyzed Intramolecular Amidation of Carbamates

The potential‐energy surfaces of the reactions of dirhodium tetracarboxylate (Rh₂^II,II) catalyzed nitrene (NR) insertion into C H bonds were examined by a DFT computational study. A pure Becke exchange functional (B88) rather than a hybrid exchange functional (B3, BHandH) was found to be appropriate for the calculation of the energy difference between the singlet and triplet Rh₂^II,II–NH nitrene species. Rh₂^II,II–NR¹ (R¹=(S)‐2‐methyl‐1‐butylformyl) is thermodynamically more favorable with a free energy lower than that of Rh₂^II,II–N(PhI)R¹. The singlet and triplet states of Rh₂^II,II–NR¹ have similar stability. Singlet Rh₂^II,II–NR¹ undergoes a concerted NR insertion into the C H bond with simultaneous formation of the N H and N C bonds during C H bond cleavage; triplet Rh₂^II,II–NR¹ undergoes H atom abstraction to produce a diradical, followed by subsequent bond formation by diradical recombination. The singlet pathway is favored over the triplet in the context of the free energy of activation and leads to the retention of the chirality of the C atom in the NR insertion product. The reactivities of the C H bonds toward the nitrene‐insertion reaction follow the order tertiary>secondary>primary. Relative reaction rates were calculated for the six reaction pathways examined in this work.     

Mechanistic Insights into the Rhenium‐Catalyzed Alcohol‐To‐Olefin Dehydration Reaction

Rhenium‐based complexes are powerful catalysts for the dehydration of various alcohols to the corresponding olefins. Here, we report on both experimental and theoretical (DFT) studies into the mechanism of the rhenium‐catalyzed dehydration of alcohols to olefins in general, and the methyltrioxorhenium‐catalyzed dehydration of 1‐phenylethanol to styrene in particular. The experimental and theoretical studies are in good agreement, both showing the involvement of several proton transfers, and of a carbenium ion intermediate in the catalytic cycle.     

Theoretical Study on the Mechanism of Ni‐Catalyzed Alkyl–Alkyl Suzuki Cross‐Coupling

Ni‐catalyzed cross‐coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl–alkyl bonds. The mechanism of this reaction with the Ni/ L1 ( L1 =trans‐N,N′‐dimethyl‐1,2‐cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni^I–Ni^III catalytic cycle with three main steps: transmetalation of [Ni^I( L1 )X] (X=Cl, Br) with 9‐borabicyclo[3.3.1]nonane (9‐BBN)R₁ to produce [Ni^I( L1 )(R₁)], oxidative addition of R₂X with [Ni^I( L1 )(R₁)] to produce [Ni^III( L1 )(R₁)(R₂)X] through a radical pathway, and C? C reductive elimination to generate the product and [Ni^I( L1 )X]. The transmetalation step is rate‐determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol^?1). On the other hand, the cross‐coupling of alkyl chlorides can be catalyzed by Ni/ L2 ( L2 =trans‐N,N′‐dimethyl‐1,2‐diphenylethane‐1,2‐diamine) because the activation barrier of transmetalation with L2 is lower than that with L1 . Importantly, the Ni⁰–Ni^II catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni^II( L1 )(R₁)(R₂)] is very difficult.     

Efficient Pd‐Catalyzed Allene Synthesis from Alkynes and Aryl Bromides through an Intramolecular Base‐Assisted Deprotonation (iBAD) Mechanism

An optimized ligand‐controlled palladium‐catalyzed allene synthesis starting from alkynes and aryl bromides giving rise to allene products in a simple and direct manner is described. The methodology is performed in an inter‐ and intramolecular fashion with unprecedented scope and excellent yields. Based on mechanistic investigations and on DFT calculations, the role played by the carboxylic additive (i.e., PivOH) in controlling the selectivity of the reaction is discussed, allowing us to propose an intramolecular base‐assisted deprotonation (iBAD) mechanism for this process.     

σ‐Insertive Mechanism versus Concerted Non‐insertive Mechanism in the Intramolecular Hydroamination of Aminoalkenes Catalyzed by Phenoxyamine Magnesium Complexes: A Synthetic and Computational Study

The phenoxyamine magnesium complexes [{ONN}MgCH₂Ph] ( 4 a : {ONN}=2,4‐tBu₂‐6‐(CH₂NMeCH₂CH₂NMe₂)C₆H₂O^?; 4 b : {ONN}=4‐tBu‐2‐(CH₂NMeCH₂CH₂NMe₂)‐6‐(SiPh₃)C₆H₂O^?) have been prepared and investigated with respect to their catalytic activity in the intramolecular hydroamination of aminoalkenes. The sterically more shielded triphenylsilyl‐substituted complex 4 b exhibits better thermal stability and higher catalytic activity. Kinetic investigations using complex 4 b in the cyclisation of 1‐allylcyclohexyl)methylamine ( 5 b ), respectively, 2,2‐dimethylpent‐4‐en‐1‐amine ( 5 c ), reveal a first‐order rate dependence on substrate and catalyst concentration. A significant primary kinetic isotope effect of 3.9±0.2 in the cyclisation of 5 b suggests significant N?H bond disruption in the rate‐determining transition state. The stoichiometric reaction of 4 b with 5 c revealed that at least two substrate molecules are required per magnesium centre to facilitate cyclisation. The reaction mechanism was further scrutinized computationally by examination of two rivalling mechanistic pathways. One scenario involves a coordinated amine molecule assisting in a concerted non‐insertive N?C ring closure with concurrent amino proton transfer from the amine onto the olefin, effectively combining the insertion and protonolysis step to a single step. The alternative mechanistic scenario involves a reversible olefin insertion step followed by rate‐determining protonolysis. DFT reveals that a proton‐assisted concerted N?C/C?H bond‐forming pathway is energetically prohibitive in comparison to the kinetically less demanding σ‐insertive pathway (ΔΔG^≠=5.6 kcal mol^?1). Thus, the σ‐insertive pathway is likely traversed exclusively. The DFT predicted total barrier of 23.1 kcal mol^?1 (relative to the {ONN}Mg pyrrolide catalyst resting state) for magnesium?alkyl bond aminolysis matches the experimentally determined Eyring parameter (ΔG^≠=24.1(±0.6) kcal mol^?1 (298 K)) gratifyingly well.     

过渡金属催化的醇类脱氧脱水反应

开发和利用环境保护型的可再生新能源是缓和与解决能源环境问题的重要举措.生物质可作为燃料和可再生平台化学品的来源.高含氧量与过度官能化的生物质原料不能直接使用,因此降低生物质原料的含氧量并将其转化为燃料与增值化学品的方法是实现生物质能广泛应用的关键.还原脱氧的方法主要有热解、水解、氢解、脱羧/脱羰反应、加氢脱氧与脱氧脱水反应等.本综述详细介绍了铼、钼、钒、钌等四种过渡金属催化的由二元醇及多元醇制备相应烯烃的脱氧脱水反应,主要从均相催化、还原剂使用、机理研究和非均相催化等方面做了多角度的总结.铼催化的脱氧脱水反应具有选择性好和烯烃产率高等优点,钼、钒、钌等金属是可能替代昂贵的铼金属的催化剂.     

Palladium‐Catalyzed Desymmetrization of Silacyclobutanes with Alkynes to Silicon‐Stereogenic Silanes: A Density Functional Theory Study

The palladium‐catalyzed desymmetrization of silacyclobutanes using electron‐deficient alkynes proceeds with high enantioselectivity in the presence of a chiral P ligand; this provides a facile approach for the synthesis of novel silicon‐stereogenic silanes. In this work, we used hybrid density functional theory (DFT) to elucidate the mechanism of the palladium‐catalyzed desymmetrization of silacyclobutanes with dimethyl acetylenedicarboxylate. Full catalytic cycle including two different initiation modes that were proposed to be a possible initial step to the formation of the 1‐pallada‐2‐silacyclopentane/alkyne intermediate—the oxidative addition of the palladium complex to the silacyclobutane Si?C bond (cycle MA) or coordination of the Pd⁰ complex with the alkyne C≡C bond (cycle MB)—have been studied. It was found that the ring‐expansion reaction began with cycle MB is energetically more favorable. The formation of a seven‐membered metallocyclic Pd^II intermediate was found to be the rate‐determining step, whereas the enantioselectivity‐determining step, oxidative addition of silacyclobutane to the three‐membered metallocyclic Pd^II intermediate, was found to be quite sensitive to the steric repulsion between the chiral ligand and silacyclobutane.     

Stereoselective Triplet‐Sensitised Radical Reactions of Furanone Derivatives

The stereo‐ and regioselectivity of triplet‐sensitised radical reactions of furanone derivatives have been investigated. Furanones 7 a , b were excited to the ³ππ* state by triplet energy transfer from acetone. Intramolecular hydrogen abstraction then occurred such that hydrogen was transferred from the tetrahydropyran to the β position of the furanone moiety. Radical combination of the tetrahydropyranyl and the oxoallyl radicals led to the final products 8 a , b . In the intramolecular reaction, overall, a pyranyl group adds to the α position of the furanone. The effect of conformation was first investigated with compounds 9 a , b carrying an additional substituent on the tether between the furanone and pyranyl moiety. Further information on the effect of conformation and the relative configuration at the pyranyl anomeric centre and the furanone moiety was obtained from the transformations of the glucose derivatives 12 , 14 , 17 and 18 . Radical abstraction occurred at the anomeric centre and at the 5′‐position of the glucosyl moiety. Computational studies of the hydrogen‐abstraction step were carried out with model structures. The activation barriers of this step for different stereoisomers and the abstraction at the anomeric centre and at the 6‘‐position of the tetrahydropyranyl moiety were calculated. The results of this investigation are in accordance with experimental observations. Furthermore, they reveal that the reactivity and regioselectivity are mainly determined in the hydrogen‐abstraction step. Intramolecular hydrogen abstraction (almost simultaneous electron and proton transfer) in ³ππ* excited furanones only takes place under restricted structural conditions in a limited number of conformations that are defined by the relative configuration of the substrates. It is observed that in the biradical intermediate, back‐hydrogen transfer occurs leading to the starting compound. In the case of glucose derivatives, this reaction led to epimerisation at the anomeric centre.     

Mechanistic Origin of Chemoselectivity in Thiolate‐Catalyzed Tishchenko Reactions

The thiolate‐catalyzed Tishchenko reaction has shown high chemoselectivity for the formation of double aromatic‐substituted esters. In the present study, the detailed reaction mechanism and, in particular, the origin of the observed high chemoselectivity, have been studied with DFT calculations. The catalytic cycle mainly consisted of three steps: 1,2‐addition, hydride transfer, and acyl transfer steps. The calculation results reproduce the experimental observations that 4‐chlorobenzaldehyde acts as the hydrogen donor (carbonyl part in the ester product), while 2‐methoxybenzaldehyde acts as the hydrogen acceptor (alcohol part in the product). The two main factors are responsible for such chemoselectivity: 1) in the rate‐determining hydride transfer step, the para‐chloride substituent facilitates the hydride‐donating process by weakening the steric hindrance, and 2) the ortho‐methoxy substituent facilitates the hydride‐accepting process by stabilizing the magnesium center (by compensating for the electron deficiency).     

Mechanism of Phosphine‐Catalyzed Allene Coupling Reactions: Advances in Theoretical Investigations

Organocatalysis has emerged as an effective strategy for chemical synthesis. Within this area, phosphine‐catalyzed coupling reactions have attracted considerable attention because of their versatility and wide range of applications in the construction of new C?C bonds. Recently, various experimental studies on the phosphine‐catalyzed coupling reaction of allenes have been reported, and mechanistic and computational studies have also progressed considerably. As a nucleophile, phosphine can react with an allene to form a zwitterionic phosphoniopropenide intermediate. After stepwise cycloaddition and proton transfer, the phosphine catalyst can be regenerated by C?P bond cleavage. Alternatively, the zwitterionic phosphoniopropenide intermediate could also be protonated by a Brønsted acid to generate a phosphonium intermediate, which can be used to construct new C?C bonds by electrophilic addition. In this review, we have summarized details of mechanistic studies of phosphine‐catalyzed allene coupling reactions that follow these two reaction modes. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of the phosphine‐catalyzed allene coupling reaction are also discussed in this review.     

Mechanistic Investigation of the Ruthenium–N‐Heterocyclic‐Carbene‐Catalyzed Amidation of Amines with Alcohols

The mechanism of the ruthenium–N‐heterocyclic‐carbene‐catalyzed formation of amides from alcohols and amines was investigated by experimental techniques (Hammett studies, kinetic isotope effects) and by a computational study with dispersion‐corrected density functional theory (DFT/M06). The Hammett study indicated that a small positive charge builds‐up at the benzylic position in the transition state of the turnover‐limiting step. The kinetic isotope effect was determined to be 2.29(±0.15), which suggests that the breakage of the C? H bond is not the rate‐limiting step, but that it is one of several slow steps in the catalytic cycle. Rapid scrambling of hydrogen and deuterium at the α position of the alcohol was observed with deuterium‐labeled substrates, which implies that the catalytically active species is a ruthenium dihydride. The experimental results were supported by the characterization of a plausible catalytic cycle by using DFT/M06. Both cis‐dihydride and trans‐dihydride intermediates were considered, but when the theoretical turnover frequencies (TOFs) were derived directly from the calculated DFT/M06 energies, we found that only the trans‐dihydride pathway was in agreement with the experimentally determined TOFs.     

Mechanism of Ketone Allylation with Allylboronates as Catalyzed by Zinc Compounds: A DFT Study

The mechanism of the allylation reaction between 4‐chloroacetophenone and pinacol allylboronates catalyzed by ZnEt₂ with alcohols was investigated using density functional theory (DFT) at the M05‐2X/6‐311++G(d,p) level. The calculations reveal that the reaction prefers to proceed through a double γ‐addition stepwise reaction mechanism rather than a Lewis acid‐catalyzed concerted one. The intermediate with a four‐coordinated boron center, which is formed through proton transfer from EtOH to the ethyl group of ZnEt₂ mediated by the boron center, is the active species and an entrance for the catalytic cycle. The latter is composed of three elementary steps: 1) boron to zinc transmetalation leading to the formation of allylzincate species, 2) electrophilic addition of ketone to allylzincate species, and 3) generation of the final product with recovery of the catalyst. The boron to zinc transmetalation step has the largest energy barrier of 61.0 kJ mol^?1 and is predicted to be the rate‐determining step. The calculations indicate that the additive EtOH plays important roles both in lowering the activation free energy for the formation of the four‐coordinated boron active intermediate and in transforming the low catalytic activity ZnEt₂ into high activity zinc alkoxide species. The alcohols with a less sterically encumbering R group might be the effective additives. The substituted groups on the allylboronates might primarily affect the boron to zinc transmetalation, and the allylboronates with substituents on the C_γ atom is poor in reactivity. The comparison of the catalytic effect between the zinc compounds investigated suggest that Zn(OEt)₂, Zn(OH)₂, and ZnF₂ exhibit higher catalytic efficiency for the boron to zinc transmetalation due to the activation of the B? C_α bond through orbital interactions between the p orbitals of the EtO, OH, F groups and the empty p orbital of the boron center.     

Multinuclear Diffusion NMR Spectroscopy and DFT Modeling: A Powerful Combination for Unraveling the Mechanism of Phosphoester Bond Hydrolysis Catalyzed by Metal‐Substituted Polyoxometalates

A detailed reaction mechanism is proposed for the hydrolysis of the phosphoester bonds in the DNA model substrate bis(4‐nitrophenyl) phosphate (BNPP) in the presence of the Zr^IV‐substituted Keggin type polyoxometalate (Et₂NH₂)₈[{α‐PW₁₁O₃₉Zr(μ‐OH) (H₂O)}₂] ? 7 H₂O (ZrK 2:2) at pD 6.4. Low‐temperature ³¹P DOSY spectra at pD 6.4 gave the first experimental evidence for the presence of ZrK 1:1 in fast equilibrium with ZrK 2:2 in purely aqueous solution. Moreover, theoretical calculations identified the ZrK 1:1 form as the potentially active species in solution. The reaction intermediates involved in the hydrolysis were identified by means of ¹H/³¹P NMR studies, including EXSY and DOSY NMR spectroscopy, which were supported by DFT calculations. This experimental/theoretical approach enabled the determination of the structures of four intermediate species in which the starting compound BNPP, nitrophenyl phosphate (NPP), or the end product phosphate (P) is coordinated to ZrK 1:1. In the proposed reaction mechanism, BNPP initially coordinates to ZrK 1:1 in a monodentate fashion, which results in hydrolysis of the first phosphoester bond in BNPP and formation of NPP. EXSY NMR studies showed that the bidentate complex between NPP and ZrK 1:1 is in equilibrium with monobound and free NPP. Subsequently, hydrolysis of NPP results in P, which is in equilibrium with its monobound form.     

Mechanism of Nickel‐Catalyzed Suzuki–Miyaura Coupling of Amides

The Ni‐catalyzed Suzuki–Miyaura coupling of N ‐tert‐butoxycarbonyl (N ‐Boc)‐protected amides provides a versatile strategy for the construction of C−C bonds. In this study, density functional theory (DFT) methods have been used to elucidate the mechanism of this reaction, with particular emphasis on the roles of N ‐Boc, K₃PO₄ and H₂O. Our results corroborated those of previous reports, indicating that the overall catalytic cycle consists of three steps, including oxidative addition, transmetalation, and reductive elimination. Three of the possible transmetalation mechanisms were examined to interpret the effects of K₃PO₄ and H₂O. According to the most feasible of these transmetalation mechanisms, K₃PO₄ (acting as a Lewis base) would initially interact with the Lewis acid PhBpin to give a K₃PO₄‐PhBpin complex, which would readily undergo a hydrogen transfer step with H₂O. The H transfer in the transmetalation step was determined to be the rate‐determining step. Notably, the theoretical results showed good agreement with the experimental data.