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Pd‐catalyzed spiroannulation of bromophenylnaphthalenols with acetylenes to achieve asymmetric dearomatization is a powerful way to construct chiral spiro‐compounds. DFT calculations with the M06 functional have been performed to reveal the mechanism and enantioselectivity of this reaction. After reversible oxidative addition of aryl bromide to Pd(0), acetylene insertion into the Pd−C(aryl) bond is considered to be the rate‐ and enantioselectivity determining step. Subsequent deprotonation and reductive elimination then give the spiroannulation product. The overlay and noncovalent interaction analysis of the critical transition states were used to reveal the origin of the enantioselectivity for this reaction. We found that the axial chirality of the naphthol moiety affects the relative free energies of the corresponding transition states, whereas the enantioselectivity is controlled by the steric repulsion between the naphthol moiety and the ligand. [ABSTRACT FROM AUTHOR]

A theoretical study of the mechanism and regioselectivity of 1,3‐dipolar cycloaddition of nitrile oxides to 3‐methylene indolone has been performed by density functional theory at the M06‐2X/6‐311++G(d,p) level of theory. The results indicate that the concerted pathway is more favorable than the stepwise pathway. Investigation of the regioselectivity of this reaction shows that the main product is predicted to be 3,5‐substituted isoxazoline derivatives, which is consistent with experimental observations. The substituent effect of nitrile oxides on the reactivity and regioselectivity were also investigated. The opposite regioselectivity was observed for nitrile oxides with electron‐donating groups (methyl and phenyl) compared with electron‐withdrawing groups (CN and CO2Me). Distortion–interaction energy analysis shows that the reactivity of 1,3‐dipolar cycloaddition of nitrile oxides to 3‐methylene indolone is controlled by both the distortion and interaction energies. Natural population analysis indicates that the carbon atom of the 1,3‐dipole prefers to bond to the terminal carbon atom of the exocyclic double bond of 3‐methylene indolone, forming the 3,5‐substituted isoxazoline product. Frontier molecular orbital analysis shows that the regioselectivity is controlled by the orbital interaction between the lowest unoccupied molecular orbital of the nitrile oxide and the highest occupied molecular orbital of 3‐methylene indolone. [ABSTRACT FROM AUTHOR]

The mechanisms of N‐heterocyclic carbene (NHC)‐catalyzed dearomatization reaction of alkyl pyridinium have been intensively studied using the density functional theory (DFT) method. The chemoselectivity and stereoselectivity were both analyzed based on the established mechanisms. The computational results showed that the chemoselective C4‐addition occurred before the C2‐addition, which is mainly because the C4 atom was more reactive according to the local reactivity analysis. The stereoselectivity was also investigated, and the C−C bond formation step was identified as the stereoselectivity‐determining step. The C−H⋅⋅⋅F and O−H⋅⋅⋅N interactions are identified as the main factors that govern the stereoselectivity by NCI analysis, and the preferred product was the RS‐configuration. This theoretical investigation would provide a case for understanding and predicting the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium. [ABSTRACT FROM AUTHOR]

The crucial need for quality refined sugar has led to the development of advanced adsorbents, with a focus on the decolorization of remelt syrup. In this study, (3-chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel (CP-PPA) was fabricated, and synthetic melanoidins were used as model colorants of remelt syrup to evaluate the validity and practicality of CP-PPA for eliminating colored impurities. Integrating abundant amine-functionalized groups (quaternary ammonium and protonated amine) within the pomelo peel-derived aerogel directionally captured electronegative melanoidins via electrostatic interactions. Furthermore, the active sites, types, and relative strength of the weak interactions between CP-PPA and melanoidins were determined using density functional theory simulations. CP-PPA exhibited an excellent equilibration adsorbing capacity for capturing melanoidins of 749.51 mg/g, and a removal efficiency of 93.69 %. Additionally, the adsorption mechanism was thoroughly examined in an effort to improve the economy of the sugar refinement industry. [Display omitted] • Pomelo peel was exploited to make cost-effective and non-toxic aerogel. • Well-developed porous network-like CP-PPA was prepared and characterized. • The absorption mechanism was deciphered by the phenomenological models. • The possible donor–acceptor adsorption relationship was vividly presented. [ABSTRACT FROM AUTHOR]

Silaspiranes have attracted particular attention due to their chiral spiro‐silicon center, which serves as an ideal carbon isostere and can endow spiro‐analogs with distinct properties. Distinct from previously reported cyclization or cycloaddition strategies to form 5/5‐silaspiranes, we report herein the asymmetric dual ring expansion of spirosilabicyclobutanes with alkynes to synthesize axially chiral spirosilabicyclohexenes bearing a novel 6/6‐silaspirane framework. DFT (density functional theory) calculations provide the deep insight into the origin of the high enantioselectivity controlled by the sterically demanding binaphthyl phosphoramidite ligand. Preliminary studies of chiroptical properties indicate that one of the spirosilabicyclohexene analogs exhibit fluorescence emission, Cotton effects and CPL (circularly polarized luminescence) activity. [ABSTRACT FROM AUTHOR]

Silaspiranes have attracted particular attention due to their chiral spiro‐silicon center, which serves as an ideal carbon isostere and can endow spiro‐analogs with distinct properties. Distinct from previously reported cyclization or cycloaddition strategies to form 5/5‐silaspiranes, we report herein the asymmetric dual ring expansion of spirosilabicyclobutanes with alkynes to synthesize axially chiral spirosilabicyclohexenes bearing a novel 6/6‐silaspirane framework. DFT (density functional theory) calculations provide the deep insight into the origin of the high enantioselectivity controlled by the sterically demanding binaphthyl phosphoramidite ligand. Preliminary studies of chiroptical properties indicate that one of the spirosilabicyclohexene analogs exhibit fluorescence emission, Cotton effects and CPL (circularly polarized luminescence) activity. [ABSTRACT FROM AUTHOR]

Both aryne 1,4‐disubstitution and 1,2,4‐trifunctionalization were accomplished from tertiary amines bearing a penta‐2,4‐dien‐1‐yl moiety. These transformations could directly incorporate a C−N and a C−C bond para to each other on an aryne intermediate via a sequential nucleophilic addition and [5,5]‐sigmatropic rearrangement. When arynes bearing 3‐tethered electrophiles were employed, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]‐sigmatropic rearrangement process was observed. Our density functional theory (DFT) calculations revealed that hydrogen‐bonding interactions between two C−H hydrogens on the penta‐2,4‐dien‐1‐yl chain and the oxygen anion generated upon N‐nucleophilic annulation reaction in the [5,5]‐sigmatropic rearrangement step is responsible for the remote diastereoselective control in this reaction system. [ABSTRACT FROM AUTHOR]

Both aryne 1,4‐disubstitution and 1,2,4‐trifunctionalization were accomplished from tertiary amines bearing a penta‐2,4‐dien‐1‐yl moiety. These transformations could directly incorporate a C−N and a C−C bond para to each other on an aryne intermediate via a sequential nucleophilic addition and [5,5]‐sigmatropic rearrangement. When arynes bearing 3‐tethered electrophiles were employed, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]‐sigmatropic rearrangement process was observed. Our density functional theory (DFT) calculations revealed that hydrogen‐bonding interactions between two C−H hydrogens on the penta‐2,4‐dien‐1‐yl chain and the oxygen anion generated upon N‐nucleophilic annulation reaction in the [5,5]‐sigmatropic rearrangement step is responsible for the remote diastereoselective control in this reaction system. [ABSTRACT FROM AUTHOR]

We report herein a highly efficient palladium‐catalyzed carbene insertion into strained Si−C bonds of benzosilacyclobutanes, which provides an efficient method to access α‐chiral silanes. With a sterically hindered ligand, carbene insertion into the C(sp3)−Si bond of benzosilacyclobutanes occurred in excellent site‐ and enantioselectivity, while C(sp2)−Si bond insertion occurred selectively with less sterically hindered ligands. Reaction mechanism, in particular the roles of the chiral ligands in controlling the site‐selectivity of the insertion reactions, are elucidated by using hybrid density functional theory. [ABSTRACT FROM AUTHOR]

Computations and experiments leading to new chiral phosphoric acids (CPAs) for epoxide thionations are reported. Density functional theory calculations reveal the mechanism and origin of the enantioselectivity of such CPA‐catalyzed epoxide thionations. The calculated mechanistic information was used to design new efficient CPAs that were tested experimentally and found to be highly effective. Bulky ortho‐substituents on the 3,3′‐aryl groups of the CPA are important to restrict the position of the epoxide in the key transition states for the enantioselectivity‐determining step. Larger para‐substituents significantly improve the enantioselectivity of the reaction. [ABSTRACT FROM AUTHOR]

Computations and experiments leading to new chiral phosphoric acids (CPAs) for epoxide thionations are reported. Density functional theory calculations reveal the mechanism and origin of the enantioselectivity of such CPA‐catalyzed epoxide thionations. The calculated mechanistic information was used to design new efficient CPAs that were tested experimentally and found to be highly effective. Bulky ortho‐substituents on the 3,3′‐aryl groups of the CPA are important to restrict the position of the epoxide in the key transition states for the enantioselectivity‐determining step. Larger para‐substituents significantly improve the enantioselectivity of the reaction. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculation has been used to reveal the mechanism of the Pd-catalyzed disilylation reaction of aryl halides. The DFT calculations indicate that the reaction starts with the oxidative addition of the C–I bond to the Pd(0) catalyst. Concerted metalation–deprotonation (CMD) can then generate a five-membered palladacycle. Insertion of Pd(II) into the Si–Si bond in disilane followed by two sequential steps of reductive eliminations yields the disilylation product and regenerates the Pd(0) catalyst. According to the NPA charge analysis along the reaction coordinates, the formal oxidative addition of the Si–Si bond to palladium could be considered as the insertion of palladium into the Si–Si bond. However, the conventional oxidative addition of the C–I bond to palladium is exactly an oxidation process with the electron transfer from the palladium atom to the C–I bond. Therefore, electron rich Pd(0) is beneficial for the oxidation process, and Pd(II) prone to acquire electrons is beneficial for the insertion process. [ABSTRACT FROM AUTHOR]

The umpolung reaction catalyzed by N‐heterocyclic carbenes (NHCs) has been widely studied and well recognized, but their role in the nonpolar inversion reaction under oxidative condition has been rarely reported. In this paper, the mechanism of the oxidative nonpolar inversion reaction catalyzed by NHCs to produce benzoxazole is investigated in detail. The reaction occurs through five processes. For oxidation in the second process, two successive tautomerizations followed by oxidation are energetically more favorable than the other two pathways. The rate‐determining step is the oxidation by 3,3′‐5,5′‐tetra‐tert‐butyl‐4,4′‐diphenoquinone. Mechanism calculations of the uncatalyzed reaction reveal that the very highly exothermic nature of the initial step is the main reason for the extremely high energy barrier in the following step. With the participation of NHC, this unfavorable transformation can be deftly prevented according to the specific sequence and equivalent of reagent addition, enabling the reaction to occur under mild conditions. [ABSTRACT FROM AUTHOR]

A mixture of pathways including the use of catalyst was proposed for a dirhodium-mediated triazole activation–cycloaddition. This proposal was supported by the results of density functional theory (DFT) calculations, and was indicated to involve a non-catalyzed cleavage of the triazole N–N bond followed by a dirhodium-assisted denitrogenation. Electron-deficient carboxylates were found to be favourable for the rate-determining denitrogenation step. [ABSTRACT FROM AUTHOR]

In this study, density functional theory (DFT) calculations were performed to gain insight into the possible reaction mechanism and substituent effects of benzene arylation at the molecular level. The results showed that both [Me3Si]+[WCA]− and [Et3Si]+[WCA]− promoted the reaction. The whole catalytic cycle generally involved three processes, namely, carbocation formation, Wheland intermediate formation, and catalyst regeneration. For the second process, the stepwise mechanism (C−C coupling followed by proton transfer) was shown to be preferred over the concerted mechanism, with successive [1,2]/[1,4]‐proton transfer as the preferred pathway. C−C coupling, rather than C−H insertion, was shown to be the rate‐determining step of the reaction, which was consistent with the kinetic isotope effect experimental results. Bond dissociation energy calculations showed that the ortho‐TMS substituent played a major role in activating the C−F bond to facilitate phenyl cation formation, leading to the most weakly C−Cl bonded intermediate, which facilitated the C−C coupling. Ortho‐phenyl substituents resulted in more severe steric hindrance of fluoride abstraction and a weaker C−H⋅⋅⋅π interaction in the C−C coupling transition state compared with meta‐phenyl substituents. Better stabilization of the cation center by an electron‐rich meta‐substituent was concluded to be the main reason for the better yield obtained compared with substrates containing an electron‐deficient meta‐substituent. [ABSTRACT FROM AUTHOR]

The possible mechanisms and origin of the enantioselectivity of the reaction between 2H‐azirine and an aldehyde catalyzed by an N‐heterocyclic carbene (NHC) were theoretically studied and predicted at the M06‐2X/6‐31G(d,p)/IEF‐PCMMTBE//M06‐2X‐GD3/6‐311++G(2df, 2pd)/IEF‐PCMMTBE level. The most favorable reaction pathway consists of four steps, i.e. complexation of the NHC and the aldehyde, stepwise [1,2]‐proton transfer, C−C bond formation coupled with another proton transfer, and recycling of the NHC. The computational results indicate that the stereoselectivity‐determining step is also the rate‐determining step, which is the third step (i.e. intermolecular addition). The calculated 99 % ee is very close to the experimentally observed value of 96 % ee, demonstrating that the calculations are reliable. Two important roles of the NHC were identified by global reaction index (GRI) analysis and natural population analysis (NPA), that is, realizing the umpolung reactivity of the aldehyde and facilitating the deprotonation of aldehyde. Moreover, the efficiency of different NHC catalysts can be mainly predicted by computing the nucleophilic index of the corresponding Breslow intermediates. Furthermore, distortion/interaction and noncovalent interaction (NCI) analyses revealed that the π⋅⋅⋅π interactions between the NHC and substrates were the key factor in the reaction enantioselectivity. [ABSTRACT FROM AUTHOR]

The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction. [ABSTRACT FROM AUTHOR]

Palladium (Pd)‐catalyzed radical oxidative C−H carbonylation of alkanes is a useful method for functionalizing hydrocarbons, but there is still a lack of understanding of the mechanism, which restricts the application of this reaction. In this work, density functional theory (DFT) calculations were carried out to study the mechanism for a Pd‐catalyzed radical esterification reaction. Two plausible reaction pathways have been proposed and validated by DFT calculations. The computational results reveal that the generated alkyl radical prefers to add to the carbon monoxide (CO) molecule to form a carbonyl radical before bonding with the Pd species. Radical addition onto Pd followed by CO migratory insertion was unfavorable owing to the high energy barrier of the migratory insertion step. The regioselectivity of the C(sp3)−H carbonylation was also investigated by DFT. The results show that the regioselectivity is controlled by both the bond dissociation energy of the reacting C−H bond and the stability of the corresponding generated carbon radical. Competitive side reactions also affected the yield and regioselectivity owing to the rapid consumption of the stable radical intermediate. Carbonylation mechanism: DFT method M06‐L was used to investigate the mechanism of Pd‐catalyzed radical oxidative carbonylation of alkanes with alcohols to afford alkyl acid esters. The results show alkyl radicals prefer to add to the CO molecule to form a carbonyl radical before bonding with the Pd species. Regioselectivity is controlled by both the bond dissociation energy of reacting the C−H bond and the stability of the corresponding generated carbon radical. [ABSTRACT FROM AUTHOR]

Graphical abstract Theoretical advances on the mechanistic study of Ag-catalyzed carbene/nitrene/silylene transfer reactions were summarized in this review, which could be considered to involve two major steps: Ag–carbene/nitrene/silylene complex formation and the subsequent transformation of these complexes. Highlights • DFT studies on the mechanism of Ag-catalyzed group transfer reactions are summarized. • The mechanism consists of Ag–carbene/nitrene/silylene formation and transformation. • The mechanism is related to the electronic behaviors of Ag–carbene/nitrene/silylene. Abstract Carbene and its isoelectronic species nitrene and silylene, have long been considered reactive intermediates in organic synthesis. Ag-catalyzed carbene/nitrene/silylene transfer reactions have emerged as an important topic because they have made remarkable progress in organic synthesis. A series of theoretical investigations on the mechanism of these reactions is important to ensure their thorough understanding and aid design of new synthetic methodologies. Here, a mechanistic overview of Ag-catalyzed carbene/nitrene/silylene transfer reactions is given, which can be separated into two major steps including Ag–carbene/nitrene/silylene complex formation and the subsequent transformation of these complexes. Theoretical studies revealed that Ag–carbene and Ag–silylene complexes can be considered as typical Fischer-type complexes, in which the carbene/silylene moiety behaves as both a sp σ donor and p π acceptor. Conversely, the triplet Ag–nitrene complexes are usually more stable than the singlet ones because of the higher electronegativity of nitrogen than those of carbon and silicon. Density functional theory calculations have indicated that the triplet state of an Ag–nitrene complex has two unpaired electrons that are mainly localized on nitrogen. In this review, theoretical studies on the generation of Ag–carbene/nitrene/silylene complexes are systematically summarized. Moreover, the nucleophilic functionalization of Ag–carbene/nitrene/silylene complexes with halogen, hydroxyl, carbonyl, alkane, or arene groups are also considered theoretically. We believe that the mechanistic details discussed here will be of great importance for rational design of desired catalytic cycles and reactions. [ABSTRACT FROM AUTHOR]

Density functional theory calculations were performed to reveal the mechanisms of Pd‐catalyzed cascade carbocyclization‐borylation and arylation reactions. The computational results indicate that the reactions start with allylic C−H cleavage through concerted metalation‐deprotonation and an intramolecular exo‐type allene insertion to form a six‐membered carbocycle intermediate. The regioselectivity of insertion could be explained by frontier molecular orbital theory and natural population analysis calculation. In the absence of extra nucleophiles, η1/η3‐isomerization followed by acetate‐assisted deprotonation could yield polyene product. When nucleophile was added to the reaction system, transmetalation and subsequent reductive elimination could give the exo‐substituted triene as major product. Meanwhile, η1/η3‐isomerization, transmetalation, and reductive elimination could afford the endo‐isomer as side product. The regioselectivity of further functionalization is controlled by the competition of transmetalation and η1/η3‐isomerization. The computational results show that both exo‐ and endo‐boronation product could be observed when bis(pinacolato)diboron is added as nucleophile. However, only exo‐phenylation product is observed when phenylboronic acid is used as nucleophile because of the high free‐energy barrier for reductive elimination from aryl η3‐allylic palladium. Show me the way: DFT calculations were employed to study the mechanism and origin of regioselectivity of cascade carbocyclization‐functionalization reactions. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) can be used to study the three‐center two‐electron (3c2e) bonding mode, which is universal in catalysts containing alkaline‐earth (Ae) and boron‐group (Bg) elements. However, because of the delocalization pattern of the 3c2e bond, the wavefunction cannot be accurately described by DFT methods. The calculated energies of Ae and Bg catalysts therefore fluctuate greatly when different functionals are used, largely because of inconsistent DFT‐calculated binding energies of 3c2e bonds. Nevertheless, with the development of supercomputers and theoretical calculation software, the DFT method is becoming increasingly popular for studying Ae and Bg catalysts. In this study, we compared the performances of 21 functionals with the high‐level composite G3B3 method in calculations for the binding energies of 3c2e bonds. Several frequently used post‐Hartree–Fock methods were also tested. The calculation results indicate that the M06‐2X, MN12‐L, and MN15 functionals give consistent and reliable binding energies for common 3c2e bonds. © 2018 Wiley Periodicals, Inc. The frequently used functionals for bonding energies were benchmarked for 3c2e systems. The results indicate that the global‐hybrid meta‐GGA functionals all performed well for 3c2e bond systems; the newly developed MN15 functional performed the best. The two meta‐NGA functionals MN12‐L and MN15‐L performed well. The inclusion of molecular mechanics did not obviously improve the performance. In conclusion, we recommend that M06‐2X, MN12‐L, and MN15 should be used in modeling of 3c2e bonding systems. [ABSTRACT FROM AUTHOR]

Density functional theory calculations were employed to elucidate the mechanism of Mn‐catalyzed chemoselective hydroarylation reactions. The Mn‐catalyzed [4+2] annulation undergoes a reaction pathway involving sequential imine‐directed C−H bond cleavage, alkyne insertion into the Mn−C bond, β‐oxygen elimination and outer catalytic cycle annulation–aromatization. Computational results demonstrated that the previously proposed chelation‐assisted alkyne insertion process was unfavorable owing to the weak coordination ability of the β‐oxygen leaving group compared with that of CO. Further noncovalent interactions analysis indicated that the origin of the high regioselectivity was contributed to the steric repulsion resulting from significant nonbonding overlap between the reacting aryl moiety and the quaternary carbon group of the reactant in the alkyne insertion step. In addition, in the Brønsted‐acid‐mediated chemoselective alkenylation reaction, the used terminal alkynes had relatively enhanced reactivity in the alkyne insertion step owing to its reduced steric repulsion. From the active alkenyl‐Mn intermediate, the activation free energy of protonation and β‐oxygen elimination are approximate, thus the alkenylated product is obtained after protonation in an acidic system. We expect that this detailed mechanistic study will significantly enhance our ability to develop Mn‐catalyzed arene C−H bond functionalization reactions. Clarity, form, and function: Density functional theory calculations were employed to elucidate the mechanism of Mn‐catalyzed chemoselective hydroarylation reactions. The Mn‐catalyzed [4+2] annulation undergoes a reaction pathway involving sequential imine‐directed C−H bond cleavage, alkyne insertion into the Mn−C bond, β‐oxygen elimination and outer catalytic cycle annulation–aromatization. [ABSTRACT FROM AUTHOR]

Selectivity control is a challenging and important subject in semihydrogenation of alkynes. Here, a combined theoretical and experimental study was performed to reveal the origin of the chemo- and stereoselectivity in cobalt-catalyzed stereodivergent semihydrogenation of alkynes. Three NNP and PNP type pincer ligands were considered in calculation. The computational results show that over-reduction of the alkene is forbidden in this catalytic system because the alkylcobalt(I) intermediate formed by alkene insertion prefers to undergo β -H elimination rather than protonation of the Co C bond. Distortion–interaction analysis along the reaction coordinate suggests that the higher distortion energy during methanol-mediated protonation of the alkylcobalt(I) species suppresses formation of the side product, thereby determined the chemoselectivity. Mechanistic investigation reveals that the active cobalt(I) hydride species formed by pre-catalyst [ C ] has strong catalytic activity for alkene isomerization. Subsequent control experiments combined with free energy comparison confirms this conclusion and reveals that fast deactivation of catalyst and the weaker reactivity of the cis-alkene intermediate in the presence of the alkyne substrate prevents Z / E alkene isomerization using pre-catalyst [ C ]. This results in the divergent stereoselectivity in the presence of different cobalt pincer complexes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: A highly para‐selective CAr−H difluoromethylation of ketoxime ethers under ruthenium catalysis has been developed. A wide variety of ketoxime ethers are compatible with the reaction, which leads to the corresponding para‐difluoromethylated products in moderate to good yield. A mechanistic study clearly showed that chelation‐assisted cycloruthenation is the key factor in the para selectivity of the difluoromethylation of ketoxime ethers. Density functional theory was used to gain a theoretical understanding of the para selectivity.# [ABSTRACT FROM AUTHOR]

The enantioselective α-addition of deconjugated butenolides has rarely been exploited, in contrast to the well-studied γ-addition of deconjugated butenolides. In this study, an unprecedented asymmetric α-addition/transesterification of deconjugated butenolides with ortho-quinone methides generated in situ afforded a series of functionalized 3,4-dihydrocoumarins containing two contiguous stereogenic centers with excellent diastereo- and enantioselectivity. DFT calculations suggested that the rarely observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic dienolate and the electrophilic ortho-quinone methide. [ABSTRACT FROM AUTHOR]

In this study, M11-L was used to evaluate the feasibility of the formation of rhodium(V) species using the rhodium(III)-catalyzed ortho-bromination of arenes as a model reaction. In most cases for these types of reactions, DFT calculations reveal that the bromination step involves a Br transfer from N-bromosuccinimide to the reacting arylrhodium to form a bromonium intermediate, followed by a Br shift to generate a new C−Br bond, which is more favorable than the previously proposed RhIII/RhV catalytic cycle. The rhodium catalyst remains in its +3 oxidation state throughout. The substituent effects of the reacting arene were studied, and computational results showed that the introduction of electron-donating groups on the reacting arene was favorable for this pathway. In contrast, the inclusion of a strong electron-withdrawing group on the aromatic ring would hinder the formation of a bromonium intermediate. Therefore, the RhIII/RhV catalytic cycle is favorable in cases that involve a RhV intermediate, which is generated by oxidative addition with NBS. In this pathway, the C−Br bond is formed by reductive elimination from the RhV intermediate. Additionally, a distortion-interaction analysis model along the reaction pathway was used to explain the directing-group effects. The results showed that the interaction energy controlled the reactivity because of the difference in electronic nature of various directing groups. [ABSTRACT FROM AUTHOR]

The first example of iron-catalyzed decarboxylative (4+1) cycloaddition reactions is described in this publication. By using this method, a wide range of functionalized indoline products were prepared from easily available vinyl benzoxazinanones and sulfur ylides in high yields and selectivities. A possible reaction pathway involving an allylic iron intermediate is discussed based on a series of control experiments and density-functional theory calculations. [ABSTRACT FROM AUTHOR]

• Density functional theoretical (DFT) calculations were performed to reveal the mechanism for nickel-catalyzed hydroaminomethylation reaction of alkyne with imine. • An alternative Ni(I) mechanism, without a redox reaction, was proposed by DFT calculations. The mechanism based on these calculations is favorable compared with the previously proposed redox Ni(0)-Ni(II) pathway. • AIM analysis shows that the dissociation of the amine ligand to provide a vacancy would lead to a higher free-energy barrier for the Ni(0)-Ni(II) pathway. Herein, we report a theoretical investigation on the nickel-catalyzed hydroaminomethylation reaction of alkyne with imine. In this work, an alternative Ni(I) mechanism, without a redox reaction, was proposed by DFT calculations. The mechanism based on these calculations is favorable compared with the previously proposed redox Ni(0)-Ni(II) pathway. A Ni(I)-amino complex is considered to be the active species, which can be obtained from hydrogen transfer between an imine-coordinated Ni(0) complex and an amine. A Meerwein-Ponndorf type hydride transfer takes place between an amino group and a coordinated alkyne. Then an imine insertion affords Ni(I)-allylamino. Proton transfer with the approaching imine yields the hydroaminomethylation product and regenerates the Ni(I)-amino active species. Throughout the catalytic cycle, the oxidative state of Ni remains at +1. Furthermore, AIM analysis shows that the dissociation of the amine ligand to provide a vacancy would lead to a higher free-energy barrier for the Ni(0)-Ni(II) pathway. An alternative Ni(I) mechanism, without a redox reaction, was proposed by DFT calculations. [Display omitted] [ABSTRACT FROM AUTHOR]

Employing the oxidative coupling of phenylacetylene with benzaldehyde as a model reaction, a density functional theory (DFT) study combined with extended X-ray absorption fine structure (EXAFS) experiment was carried out to reveal the difference between dinuclear and mononuclear zinc mediated nucleophilic addition. Newly reported DFT method M11-L computed results suggest that the mononuclear zinc mediated pathway, in which nucleophilic addition occurs via a four-membered ring transition state, is unfavourable both thermodynamically and kinetically. The dinuclear zinc mechanism, which appropriately explains the experimental observations, involves a six-membered ring transition state for nucleophilic addition. Subsequent in situ EXAFS experiment confirmed the existence of dinuclear zinc active species. Moreover, frontier molecular orbital (FMO) analysis and distortion–interaction energy analysis along the whole reaction pathways have provided interpretations for the advantage of dinuclear zinc mediated nucleophilic addition. Consequently, we believe this dinuclear zinc pathway will open up a general consideration of the dinuclear zinc mechanism for nucleophilic additions. [ABSTRACT FROM AUTHOR]

TheCo2(CO)8-mediated intramolecular Pauson–Khandreaction is an efficient approach to the trans-decalinsubunit with a defined C1 quaternary chiral center. The newly developeddensity functional theory method M11-L was employed to study the mechanism,reactivity, and stereoselectivity for this reaction. The rate- andstereoselectivity-determining step is the intramolecular alkene insertioninto the carbon–cobalt bond. Insertion of the alkene by the re- and si-face was studied to explainthe stereoselectivity. The effects of varying the substituent on theacetylene and the C3 chirality were investigated experimentally andtheoretically. [ABSTRACT FROM AUTHOR]

A transition-metal-assistedoxidative C(sp3)-H/N–Hcross-coupling reaction of N-alkoxyamides with aliphatichydrocarbons is described. During the reaction, nitrogen radicalswere generated from the oxidation of N-alkoxyamides.Experiments and DFT calculations revealed that transition-metal catalystcould lower the reactivity of the generated nitrogen radical by thecoordination of the transition metal, which allowed the selectiveradical/radical cross-coupling with the transient sp3carbonradical to construct C(sp3)–-N bonds. Various C(sp3)–H bonds could be transformed into C(sp3)–N bonds through this radical amidation strategy. [ABSTRACT FROM AUTHOR]

Higher-order cycloadditions are a powerful strategy for the construction of polycycles in one step. However, an efficient and concise version for the induction of asymmetry is lacking. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and could be an ideal choice for enantioselective higher-order cycloadditions. Here, we report an enantioselective [10 + 2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields, and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory calculations provide an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol. High-order cycloaddition reactions are useful for the construction of polycycles in a single step, but versions that induce asymmetry are limited. Here the authors report the construction of asymmetric polycycles via N-heterocyclic carbene-catalyzed hetero-[10 + 2] cycloaddition of indole-2-carbaldehydes with trifluoromethyl ketone derivatives. [ABSTRACT FROM AUTHOR]

Ir-catalysis has been widely adopted in hydrogenation reactions for the transformation of unsaturated molecules to the corresponding saturated ones. We reviewed herein the DFT studies on mechanism of Ir-catalyzed homogeneous hydrogenations with respect to various hydrogen sources. Moreover, the stereochemistry and substituent effects in the Ir-catalyzed hydrogenations are considered. • Mechanistic studies towards Ir-mediated hydrogenation were summarized in this review. • General catalytic cycles given by theoretical studies are involved in each example. • Mechanism discussions are classified according to the substrates. • The understanding of mechanism would be helpful for further design new Ir-catalysis. Ir catalysis is widely used in hydrogenation reactions to transform unsaturated molecules to the corresponding saturated molecules. Understanding the reaction mechanism is helpful for design of new Ir-catalyzed hydrogenation reactions, as well as for controlling the regio/stereoselectivity. Density functional theory is a powerful tool for mechanistic study of organometallic catalysis, and it has been widely used to reveal the reaction pathways in this research area. With the development of computational methods, much progress has recently been made in mechanistic study of Ir-catalyzed hydrogenation reactions. Herein, we present a review of theoretical studies of the mechanism of Ir-catalyzed homogeneous hydrogenation. A redox pathway is commonly proposed for hydrogenation of non-polar unsaturated bonds, which involves oxidative addition of a hydrogen molecule to afford a high valence Ir hydride complex, insertion of an unsaturated bond into the Ir–H bond, and reductive elimination. Alternatively, the dihydrogen molecule can undergo a heterolysis reaction to provide a formal hydride ion and a proton. Subsequent nucleophilic and electrophilic attack can then also achieve hydrogenation of the polar unsaturated bond. In this review, the studies of the mechanism of Ir-catalyzed hydrogenation are classified according to the type of substrate: olefins, carbonyls, and imines. In each category, the reactions are discussed with respect to the various hydrogen sources. The stereochemistry and substituent effect in Ir-catalyzed hydrogenation are also considered. [ABSTRACT FROM AUTHOR]

[Display omitted] • The mechanism and origin of selectivities of NHC-catalyzed hydroacylation-Stetter reaction has been systematically studied. • The role of NHC has been disclosed by using global reactivity index analysis. • ELF and IRC analyses are performed to clarify the bonding modes of hydroacylation and Stetter reaction. The regioselectivity of hydroacylation mediated by transition metal and organocatalyst has been and continues to be one of the most challenging questions in the synthesis field. To explore the possible mechanisms and origin of the regio-/enantioselectivity, the density functional theory (DFT) calculations were performed for studying intramolecular hydroacylation-Stetter reaction of alkynyl bisbenzaldehyde catalyzed by N-heterocyclic carbene (NHC). Computational results show that the hydroacylation process was the rate-determining step and irreversible. Four different stereoisomers (RR, RS, SR, and SS) were considered and the lowest energy mode agreed with the reported enantioselectivity in experiment. Global reaction index (GRI) analysis showed that NHC catalyst can convert alkynyl bisbenzaldehyde electrophilic carbonyl carbon into nucleophilicity to initiate the reaction. Moreover, electron localization function (ELF) and intrinsic reaction coordinate (IRC) analyses were performed to characterize the manner difference between the process of hydroacylation and Stetter reaction. [ABSTRACT FROM AUTHOR]