Theoretical prediction on the reactivity of the Co-mediated intramolecular Pauson-Khand reaction for constructing bicyclo-skeletons in natural products

This work performed a theoretical investigation to explore the mechanism and reactivity of the Co-mediated intramolecular Pauson-Khand reaction for constructing bicyclo-skeletons.     

Mechanism of the intramolecular hydroamination of alkenes catalyzed by neutral indenyltitanium complexes: a DFT study

Three mechanistic pathways for the [Ind(2)TiMe(2)]-catalyzed intramolecular hydroamination of alkenes have been investigated by employing density functional theory calculations on the possible intermediates and transition states. The results indicate that the reaction cycle proceeds via a Ti-imido-amido complex as the catalytically active species. However, at the moment, the question as to whether this imido-amido complex is involved in a [2+2]-cycloaddition with the alkene or a newly proposed insertion of the alkene into a Ti--N single bond cannot be answered; the calculated barriers of both the insertion mechanism and the [2+2]-cycloaddition mechanism are similar (143 vs. 136 kJ mol(-1)), and both pathways are in accordance with the experimentally observed rate law (first-order dependence on the aminoalkene concentration). Interestingly, the newly proposed insertion mechanism that takes place by an insertion of the alkene moiety into the Ti--N single bond of an imido-amido complex seems to be much more likely than a mechanism that involves an alkene insertion into a Ti--N single bond of a corresponding trisamide. The latter mechanism, which has been proposed in analogy to rare-earth-metal-catalyzed hydroamination reactions, can be ruled out for two reasons: a surprisingly high activation barrier (164 kJ mol(-1)) and the fact that the rate-limiting insertion step is independent of the aminoalkene concentration. This is in sharp contrast to the experimental findings for indenyltitanium catalysts.     

New mechanistic insights into the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins: a DFT and kinetic study

The reaction mechanism of the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins has been studied by means of density functional theory calculations (B3LYP) and kinetic experiments. The calculations suggest that the reaction involves an unexpected Ir(III)-Ir(V) catalytic cycle facilitated by coordination of a second equivalent of dihydrogen. Thus, in the rate-determining migratory insertion of the substrate alkene into an iridium-hydride bond, simultaneous oxidative addition of the bound dihydrogen occurs. The kinetic data shows that the reaction is first order with respect to hydrogen pressure. This is interpreted in terms of an endergonic coordination of this second equivalent of dihydrogen, although a rate-determining step, in which coordinated solvent is replaced by dihydrogen, could not be ruled out. Furthermore, the reaction was found to be zeroth order with respect to the alkene concentration. This correlates well with the calculated exothermicity of substrate coordination, and the catalyst is thus believed to coordinate an alkene in the resting state. On the basis of the proposed catalytic cycle, calculations were performed on a full-sized system with 88 atoms to assess the appropriateness of the model calculations. These calculations were also used to explain the enantioselectivity exerted by the catalyst.     

The Retro‐Hydroformylation Reaction

Hydroformylation, a reaction that adds carbon monoxide and dihydrogen across an unsaturated carbon–carbon multiple bond, has been widely employed in the chemical industry since its discovery in 1938. In contrast, the reverse reaction, retro‐hydroformylation, has seldom been studied. The retro‐hydroformylation reaction of an aldehyde into an alkene and synthesis gas (a mixture of carbon monoxide and dihydrogen) in the presence of a cyclopentadienyl iridium catalyst is now reported. Aliphatic aldehydes were converted into the corresponding alkenes in up to 91 % yield with concomitant release of carbon monoxide and dihydrogen. Mechanistic control experiments indicated that the reaction proceeds by retro‐hydroformylation and not by a sequential decarbonylation–dehydrogenation or dehydrogenation–decarbonylation process.     

AuI-Catalyzed Haloalkynylation of Alkenes

The formal insertion of alkenes into aromatic chloro- and bromoalkynes takes place under cationic gold catalysis. This haloalkynylation reaction can be performed with cyclic, gem-disubstituted and monosubstituted alkenes, using BINAP, triazolo[4,3-b]isoquinolin-3-ylidene ligands or SPhos, respectively. The products were isolated in moderate to excellent yields and with complete diastereo- and regioselectivity; the halogen atom bonding the more substituted carbon of the alkene. Preliminary experiments showed that the enantioselective haloalkynylation of cyclopentene can be performed with (S)-BINAP to afford the insertion products with moderate to good enantioselectivities.     

钯含氮配合物催化烯烃芳基化反应的密度泛函研究

用密度泛函方法(DFT)研究了Pd(II)含氮配合物催化烯烃芳基化反应的机理. 结果表明, 该反应是放热的, 主要经历了对甲苯基对烯烃的迁移插入和β-H的还原消去. 对甲苯基对烯烃的迁移插入是反应的速率控制步骤和手性控制步骤. 理论预测的产物是与实验一致的(R)-2-甲基-2-苯基环戊酮.     

A theoretical study on the mechanisms of intermolecular hydroacylation of aldehyde catalyzed by neutral and cationic rhodium complexes

In this paper, we used density functional theory(DFT) computations to study the mechanisms of the hydroacylation reaction of an aldehyde with an alkene catalyzed by Wilkinson's catalyst and an organic catalyst 2-amino-3-picoline in cationic and neutral systems. An aldehyde's hydroacylation includes three stages: the C–H activation to form rhodium hydride(stage I), the alkene insertion into the Rh–H bond to give the Rh-alkyl complex(stage II), and the C–C bond formation(stage III). Possible pathways for the hydroacylation originated from the trans and cis isomers of the catalytic cycle. In this paper, we discussed the neutral and cationic pathways. The rate-determining step is the C–H activation step in neutral system but the reductive elimination step in the cationic system. Meanwhile, the alkyl group migration-phosphine ligand coordination pathway is more favorable than the phosphine ligand coordination-alkyl group migration pathway in the C–C formation stage. Furthermore, the calculated results imply that an electron-withdrawing group may decrease the energy barrier of the C–H activation in the benzaldehyde hydroacylation.     

The final steps of the Oppolzer cyclization: mechanism of the insertion of alkenes into allylpalladium(II) complexes

We report here the results of a computational study on the the mechanism of the Oppolzer cyclization. These results lead us to conclude that the insertion of olefins in Pd-allyl complexes probably takes place directly from the eta(3)-allyl species. The presence of a phosphane ligand in the reagents plays the role of enhancing the electron density on the Pd atom; this makes the alkene moiety more reactive towards insertion by back-donation from the metal. The results also indicate that the configuration of the new stereogenic centers is fixed in the insertion of the alkene into the (eta(3)-allyl)palladium species.     

Reversible alkene insertion into the Pd-N bond of Pd(II)-sulfonamidates and implications for catalytic amidation reactions

Alkene insertion into Pd-N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd-amidate and resulting Pd-alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O(2). Electronic-effect studies reveal that alkene insertion into the Pd-N bond is favored kinetically and thermodynamically with electron-rich amidates.     

Energy-gaining formation and catalytic behavior of active structures in a SiO(2)-supported unsaturated Ru complex catalyst for alkene epoxidation by DFT calculations

The formation and catalytic behavior of active structures in a SiO(2)-supported unsaturated Ru complex catalyst for alkene epoxidation were studied by means of hybrid density functional theory (DFT) calculations. An energy-gaining route for the catalyst activation was found to allow the formation of active unsaturated Ru complexes and the remarkable alkene epoxidation via an exothermic reaction path between isobutyraldehyde and oxygen. In the proposed Bartlett mechanism, Ru promotes the formation of peracid intermediate and facilitates the intermolecular hydrogen transfer in the peracid intermediate, while alkene molecules do not directly coordinate to the Ru site. It was found that stilbene epoxidation is easier to achieve than ethene epoxidation thanks to the electron donating phenyl groups.     

Theoretical analysis of the mechanism of palladium(II) acetate-catalyzed oxidative Heck coupling of electron-deficient arenes with alkenes: effects of the pyridine-type ancillary ligand and origins of the meta-regioselectivity

A systematic theoretical study is carried out on the mechanism for Pd(II)-catalyzed oxidative cross-coupling between electron-deficient arenes and alkenes. Two types of reaction pathways involving either a sequence of initial arene C-H activation followed by alkene activation, or the reverse sequence of initial alkene C-H activation followed by arene activation are evaluated. Several types of C-H activation mechanisms are discussed including oxidative addition, σ-bond metathesis, concerted metalation/deprotonation, and Heck-type alkene insertion. It is proposed that the most favored reaction pathway should involve an initial concerted metalation/deprotonation step for arene C-H activation by (L)Pd(OAc)(2) (L denotes pyridine type ancillary ligand) to generate a (L)(HOAc)Pd(II)-aryl intermediate, followed by substitution of the ancillary pyridine ligand by alkene substrate and direct insertion of alkene double bond into Pd(II)-aryl bond. The rate- and regio-determining step of the catalytic cycle is concerted metalation/deprotonation of arene C-H bond featuring a six-membered ring transition state. Other mechanism alternatives possess much higher activation barriers, and thus are kinetically less competitive. Possible competing homocoupling pathways have also been shown to be kinetically unfavorable. On the basis of the proposed reaction pathway, the regioselectivity predicted for a number of monosubstituted benzenes is in excellent agreement with experimental observations, thus, lending further support for our proposed mechanism. Additionally, the origins of the regioselectivity of C-H bond activation is elucidated to be caused by a major steric repulsion effect of the ancillary pyridine type ligand with ligands on palladium center and a minor electronic effect of the preinstalled substituent on the benzene ring on the cleaving C-H bond. This would finally lead to the formation of a mixture of meta and para C-H activation products with meta products dominating while no ortho products were detected. Finally, the multiple roles of the ancillary pyridine type ligand have been discussed. These insights are valuable for our understanding and further development of more efficient and selective transition metal-catalyzed oxidative C-H/C-H coupling reactions.     

Reaction mechanism of palladium‐catalyzed silastannation of allenes by density functional theory

The reaction mechanism of Pd(0)‐catalyzed allenes silastannation reaction is investigated by the density functional method B3LYP. The overall reaction mechanism is examined. For the allene insertion step, the Pd Si bond is preferred over the Pd Sn bond. The electronic mechanism of the allene insertion into Pd Si bond to form σ‐vinylpalladium (terminal‐insertion) and σ‐allylpalladium (internal‐insertion) insertion products is discussed in terms of the electron donation and back‐donation. It is found that the electron back‐donation is significant for both terminal‐ and internal‐insertion. During allene insertion into Pd Si bond, internal‐insertion is preferred over terminal‐insertion. By using methylallene, the regio‐selectivity for the monosubstituted allene insertion into Pd Si and Pd Sn bond is analyzed. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009     

Reactions of carbenes in solidified organic molecules at low temperature

Studies on reactions of carbenes in reactive organic glasses at low temperatures clearly reveal that solution results and liquid phase mechanistic rules cannot be readily extrapolated to matrix conditions. Thus, the usual course of reaction of a carbene with an alkene in solution results in the formation of a cyclopropane for both the singlet and triplet states although a one-step addition possible for singlet carbene produces the cyclopropane stereospecifically and a stepwise pathway with the triplet state affords two possible stereoisomers of the cyclopropane. In a sharp contrast, the formal insertion products into the allylic C-H bonds of alkenes are produced at the expense of the cyclopropane when carbene is generated in alkene matrix at low temperature. Similar results are obtained in the reaction with alcohols, where the C-H insertion products are formed in low temperature alcoholic matrices at the expense of the O-H insertion products which are predominant products in the reaction with alcoholic solution at ambient temperature. The ¹³C labelling experiments as well as deuterium kinetic isotope effects suggest that these C-H insertion products are most probably produced from the triplet carbene, not from the singlet, by abstraction of H atom from the matrix followed by the recombination of the resulting radical pairs. Kinetic studies using ESR and laser flash photolysis techniques demonstrate that the mechanism of a H-atom transfer reaction changes from a completely classical process in a soft warm glass to a completely quantum mechanical tunneling process in a cold hard glass. Thus, as the reaction temperature is lowered, the classical reaction rate decreases, and eventually becomes much slower than decay by hydrogen atom tunneling. The members of the radical pairs which usually diffuse apart in a fluid solution are not able to diffuse apart owing to the limited diffusibility within a rigid matrix and therefore recombine with high efficiency to give the CH “insertion” products. A rather surprising and intriguing difference between the C-H insertion undergone by singlet carbenes in fluid solution at ambient temperatures and one by triplet carbenes in matrix at low temperature is noted. Thus, a marked increase in the primary and secondary C-H insertion over the tertiary is observed in the matrix reaction indicating that triplet carbenes tend to abstract H from less crowded C-H bonds. This is interpreted to indicate that the distance between carbenic center and tunneling H becomes important in H atom tunneling process. More surprisingly, the C-H insertion by triplet carbene by the abstraction-recombination mechanism in a rigid matrix proceeds with retention of the configuration, suggesting that the solid state prevents motion of the radicals to the extent that does not allow racemization to occur. Reactions with heteroatom substrates such as ethers, amines, alkyl halides and ketones are also subject to the matrix effects and the C-H insertion products increase at the expense of singlet carbene reaction products resulting from the interaction with the heteroatoms. Stereoselectivities of cyclopropanation to styrenes are also shown to be affected by the matrix effects. t-Butyl alcohol matrix is shown to be unreactive toward carbenes and thus can be used as a “solvent” in matrix carbene reactions presumably due to a large inert guest cavity provided by bulky tertiary alcohol which binds a molecular aggregate inside it. H atom tunneling in the matrix is also shown to compete with very efficient intramolecular migration of hydrogen to the carbenic center. Migration aptitude as well as stereochemistry are also found to be subject to the matrix effects.     

Borrowing hydrogen: iridium-catalysed reactions for the formation of C-C bonds from alcohols

Alcohols have been employed as substrates for C-C bond-forming reactions which involve initial activation by the temporary removal of hydrogen to form an aldehyde. The intermediate aldehyde is converted into an alkene via a Horner-Wadsworth-Emmons reaction, nitroaldol and aldol reactions. The 'borrowed hydrogen' is then returned to the alkene to form a C-C bond.     

Stereocontrolled Synthesis of Vinyl Boronates and Vinyl Silanes via Atom‐Economical Ruthenium‐Catalyzed Alkene–Alkyne Coupling

The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru‐catalyzed alkene–alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron‐ and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross‐coupling reactions, and a Chan‐Lam‐type allyloxylation followed by a Claisen rearrangement. A sequential one‐pot alkene‐alkyne‐coupling/allylation‐sequence with an aldehyde to deliver a highly complex α‐silyl‐β‐hydroxy olefin with a handle for further functionalization was also realized.     

铑催化烯烃氢甲酰化反应的密度泛函研究

在B3LYP／6-31G(d,P)(Rh和P采用LANL2DZ Polar)水平下,研究了有机膦羰基铑催化乙烯的氢甲酰化反应机理,优化了反应中间体、过渡态和产物的结构．结果表明,乙烯的氢甲酰化反应有两条主要的反应路径,经历了乙烯络合、乙烯插入、膦加成、羰基插入、H2的氧化加成和丙醛还原消除及催化剂的再生等过程．乙烯插入、羰基插入、H2的氧化加成和丙醛还原消除过程中三元环的形成是协同进行的．反应以顺式活性催化剂为起始物,H2的氧化加成是反应速度控制步骤,丙酰基的消除反应是不可逆的．理论结果与实验一致．     

Mechanism of methylacetylene bisselenation catalyzed by palladium complex from density functional study

The reaction mechanism of Pd(0)-catalyzed methylacetylene bisselenation reaction is investigated by using the density functional method. The overall reaction mechanism involves the oxidative addition, insertion, and reductive elimination steps. The regioselectivity has been investigated for the methylacetylene insertion into Pd-Se bond of both cis and trans palladium complexes. It is found that the methylacetylene insertion into Pd-Se bond of the trans palladium complex using the substituted carbon atom attached to selenyl group is preferred among the four pathways of methylacetylene insertion processes. The electronic mechanisms on the methylacetylene insertion into Pd-Se bond are discussed in terms of the Frontier molecular orbital interactions. In addition, the influence of carbon monoxide on methylacetylene bisselenation was studied and found that the methylacetylene coordination and insertion into Pd-Se bond take place first generating the Pd-C bond, followed by CO insertion into the Pd-C bond.     

Iridium-Catalyzed Remote Site-Switchable Hydroarylation of Alkenes Controlled by Ligands

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at the subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields and with good to excellent site-selectivities. The catalytic system showed good functional group tolerance and a broad substrate scope, including unactivated and activated alkenes. More importantly, the regioconvergent transformations of mixtures of isomeric alkenes were also successfully realized. The results of the mechanistic studies demonstrate that the reaction undergoes a chain-walking process to give an [Ar−Ir−H] complex of terminal alkene. The subsequent processes proceed through the modified Chalk–Harrod-type mechanism via the migratory insertion of terminal alkene into the Ir−C bond followed by C−H reductive elimination to afford the hydrofunctionalization products site-selectively.     

Mechanism of the palladium-catalyzed addition of arylboronic acids to enones: a computational study

The palladium(II)-catalyzed addition of arylboronic acids to β,β-disubstituted enones has been investigated with the BP86 density functional. The results show that the mechanism requires three steps: transmetalation, alkene insertion, and protonation. The alkene insertion is the rate-determining step. For unactivated alkenes, the Heck-type β-hydride elimination is more favored than protonation.     

Rates and mechanism of alkyne ozonation

The rates and products of the reactions of ozone with acetylene, methylacetylene, dimethylacetylene, and ethylacetylene have been studied in a long-path infrared cell at 21 ± 1°C. The gas phase reaction gives products formed by cleavage of the carbon–carbon triple bond. A mechanism is proposed that involves formation of a short-lived acid anhydride intermediate, which is energized by virtue of the reaction exothermicity and undergoes unimolecular decomposition. Formation of an α-dicarbonyl was observed in every case, but there is evidence that a side reaction on the walls accounted for that product. The general relationship between alkyne and alkene ozonation is discussed. The rate measurements showed that, unlike the alkenes, the rate of alkyne ozonation is not greatly affected by substitution with simple alkyl groups. The rate constant for C₂H₂ agrees with earlier work and thus provides additional support for the previously derived high A-factor for acetylene ozonation relative to alkenes.