Two metals are better than one in the gold catalyzed oxidative heteroarylation of alkenes

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)-Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)-Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C-C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~15 kcal/mol advantage for bimetallic reductive elimination.     

Combined experimental and computational studies on carbon-carbon reductive elimination from Bis(hydrocarbyl) complexes of (PCP)Ir

The reductive elimination of carbon-carbon bonds is one of the most fundamentally and synthetically important reaction steps in organometallic chemistry, yet relatively little is understood about the factors that govern the kinetics of this reaction. C-C elimination from complexes with the common d (6) six-coordinate configuration generally proceeds via prior ligand loss, which greatly complicates any attempt to directly measure the rates of the specific elimination step. We report the synthesis of a series of five-coordinate d (6) iridium complexes, ( (tBu)PCP)Ir(R)(R'), where R and R' are Me, Ph, and (phenyl-substituted) vinyl and alkynyl groups. For several of these complexes (R/R' = Ph/Vi, Me/Me, Me/Vi, Me/CCPh, and Vi/CCPh, where Vi = trans-CHCHPh) we have measured the absolute rate of C-C elimination. For R/R' = Ph/Ph, Ph/Me, and Ph/CCPh, we obtain upper limits to the elimination rate; and for R/R' = CCPh/CCPh, a lower limit. In general, the rates decrease (activation barriers increase) according to the following order: acetylide < vinyl approximately Me < Ph. Density functional theory (DFT) calculations offer significant insight into the factors behind this order, in particular the slow rates for elimination of the vinyl and, especially, phenyl complexes. The transition states are calculated to involve rotation of the aryl or vinyl group around the Ir-C bond, prior to C-C elimination, such that the group to which it couples can add to the face of the aryl or vinyl group. This rotation is severely hindered by the presence of the phosphino -t-butyl groups that lie above and below the plane of the aryl/vinyl group in the ground state. Accordingly, calculations predict dramatically different relative rates of elimination from the much less sterically hindered complexes ( (H)PCP)Ir(R)(R'). For example, the barrier to elimination from ( (H)PCP)Ir(Me) 2 is 20 kcal/mol, which is 2 kcal/mol greater than from the ( (tBu)PCP)Ir analogue. In contrast, the activation enthalpies calculated for vinyl-vinyl and phenyl-phenyl elimination from ( (H)PCP)Ir are remarkably low, only 2 and 9 kcal/mol, respectively; these values are 16 and 22 kcal/mol less than those of the corresponding ( (tBu)PCP)Ir complexes. Moreover, since these eliminations are very nearly thermoneutral, the barriers are calculated to be equally low for the reverse reactions [C-C oxidative addition to ( (H)PCP)Ir]. The absence of differences in intraligand CC bond lengths in the transition states relative to the ground states, combined with a comparison of calculated "face-on" and "planar" transition states for C-C coupling, suggests that the critical importance of the aryl/vinyl rotation is based on geometric or steric factors rather than electronic ones. Thus there is no evidence for participation of the pi or pi* orbitals of the aryl or vinyl groups in the formation of the C-C bond, although a small pi effect cannot be rigorously excluded. Likewise, the results do not support the hypothesis that the degree of directionality of the carbon-based orbital used for bonding to iridium (sp (3) > sp (2) > sp) plays an important role in this system in determining the barrier to reductive elimination.     

On the reduction of the number of unknowns in flory-huggins calculations of polymeric equilibria

The Flory-Huggins equations concerning equilibria of two phases within ternary systems polymer/polymer/solvent are rewritten using a new set of variables. This allows the easy elimination of one of the unknowns of the problem, which can be further simplified, through the elimination of a second unknown, within regions of the diagram sufficiently near to a critical point.     

第四级铵氢氧化物Hofmann消除反应的构象分析及反应机理

本文用DPCILO, CNDO程序分别计算了一些第四级铵离子不同构象的能量及电荷密度, 探讨Hofmann消除反应的机理, 结果表明构象规则能较好地说明Hofmann消除反应的机理, 只是“直链型”烷基的消除反应应按顺式E_2机理进行。     

The synthesis of highly functionalized morpholine N-oxides from ephedrine and pseudoephedrine utilizing a tandem Cope elimination/reverse Cope elimination protocol

Highly functionalized monocyclic morpholine N-oxides can be prepared in three steps starting from ephedrine and pseudoephedrine utlizing a tandem Cope elimination/reverse Cope elimination.     

Fragmentation reactions of protonated peptides containing glutamine or glutamic acid

A variety of protonated dipeptides and tripeptides containing glutamic acid or glutamine were prepared by electrospray ionization or by fast atom bombardment ionization and their fragmentation pathways elucidated using metastable ion studies, energy-resolved mass spectrometry and triple-stage mass spectrometry (MS(3)) experiments. Additional mechanistic information was obtained by exchanging the labile hydrogens for deuterium. Protonated H-Gln-Gly-OH fragments by loss of NH(3) and loss of H(2)O in metastable ion fragmentation; under collision-induced dissociation (CID) conditions loss of H-Gly-OH + CO from the [MH - NH(3)](+) ion forms the base peak C(4)H(6)NO(+) (m/z 84). Protonated dipeptides with an alpha-linkage, H-Glu-Xxx-OH, are characterized by elimination of H(2)O and by elimination of H-Xxx-OH plus CO to form the glutamic acid immonium ion of m/z 102. By contrast, protonated dipeptides with a gamma-linkage, H-Glu(Xxx-OH)-OH, do not show elimination of H(2)O or formation of m/z 102 but rather show elimination of NH(3), particularly in metastable ion fragmentation, and elimination of H-Xxx-OH to form m/z 130. Both the alpha- and gamma-dipeptides show formation of [H-Xxx-OH]H(+), with this reaction channel increasing in importance as the proton affinity (PA) of H-Xxx-OH increases. The characteristic loss of H(2)O and formation of m/z 102 are observed for the protonated alpha-tripeptide H-Glu-Gly-Phe-OH whereas the protonated gamma-tripeptide H-Glu(Gly-Gly-OH)-OH shows loss of NH(3) and formation of m/z 130 as observed for dipeptides with the gamma-linkage. Both tripeptides show abundant formation of the y(2)' ion under CID conditions, presumably because a stable anhydride neutral structure can be formed. Under metastable ion conditions protonated dipeptides of structure H-Xxx-Glu-OH show abundant elimination of H(2)O whereas those of structure H-Xxx-Gln-OH show abundant elimination of NH(3). The importance of these reaction channels is much reduced under CID conditions, the major fragmentation mode being cleavage of the amide bond to form either the a(1) ion or the y(1)' ion. Particularly when Xxx = Gly, under CID conditions the initial loss of NH(3) from the glutamine containing dipeptide is followed by elimination of a second NH(3) while the initial loss of H(2)O from the glutamic acid dipeptide is followed by elimination of NH(3). Isotopic labelling shows that predominantly labile hydrogens are lost in both steps. Although both [H-Gly-Glu-Gly-OH]H(+) and [H-Gly-Gln-Gly-OH]H(+) fragment mainly to form b(2) and a(2) ions, the latter also shows elimination of NH(3) plus a glycine residue and formation of protonated glycinamide. Isotopic labelling shows extensive mixing of labile and carbon-bonded hydrogens in the formation of protonated glycinamide.     

Ab initio and RRKM study of photodissociation of azulene cation

The ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) approach has been applied to investigate the photodissociation mechanism of the azulene cation at different values of the photon energy. Reaction pathways leading to various decomposition products have been mapped out at the G3(MP2,CC)//B3LYP level and then the RRKM and microcanonical variational transition state theories have been applied to compute rate constants for individual reaction steps. Relative product yields (branching ratios) for the dissociation products have been calculated using the steady-state approach. The results show that a photoexcited azulene cation can readily isomerize to a naphthalene cation. The major dissociation channels are elimination of atomic hydrogen, an H2 molecule, and acetylene. The branching ratio of the H elimination channel decreases with an increase of the photon energy. The branching ratio of the acetylene elimination as well as that of the H2 elimination rise as the photon energy increases. The main C8H6+ fragment at all photon energies considered is a pentalene cation, and its yield decreases slightly with increasing excitation energy, whereas the branching ratios of the other C8H6+ fragments, phenylacetylene and benzocyclobutadiene cations, grow.     

Mechanisms of catalyst poisoning in palladium-catalyzed cyanation of haloarenes. remarkably facile C-N bond activation in the [(Ph3P)4Pd]/[Bu4N]+ CN- system

Reaction paths leading to palladium catalyst deactivation during cyanation of haloarenes (eq 1) have been identified and studied. Each key step of the catalytic loop (Scheme 1) can be disrupted by excess cyanide, including ArX oxidative addition, X/CN exchange, and ArCN reductive elimination. The catalytic reaction is terminated via the facile formation of inactive [(CN)4Pd]2-, [(CN)3PdH]2-, and [(CN)3PdAr]2-. Moisture is particularly harmful to the catalysis because of facile CN- hydrolysis to HCN that is highly reactive toward Pd(0). Depending on conditions, the reaction of [(Ph3P)4Pd] with HCN in the presence of extra CN- can give rise to [(CN)4Pd]2- and/or the remarkably stable new hydride [(CN)3PdH]2- (NMR, X-ray). The X/CN exchange and reductive elimination steps are vulnerable to excess CN- because of facile phosphine displacement leading to stable [(CN)3PdAr]2- that can undergo ArCN reductive elimination only in the absence of extra CN-. When a quaternary ammonium cation such as [Bu4N]+ is used as a phase-transfer agent for the cyanation reaction, C-N bond cleavage in the cation can occur via two different processes. In the presence of trace water, CN- hydrolysis yields HCN that reacts with Pd(0) to give [(CN)3PdH]2-. This also releases highly active OH- that causes Hofmann elimination of [Bu4N]+ to give Bu3N, 1-butene, and water. This decomposition mode is therefore catalytic in H2O. Under anhydrous conditions, the formation of a new species, [(CN)3PdBu]2-, is observed, and experimental studies suggest that electron-rich mixed cyano phosphine Pd(0) species are responsible for this unusual reaction. A combination of experimental (kinetics, labeling) and computational studies demonstrate that in this case C-N activation occurs via an S(N)2-type displacement of amine and rule out alternative 3-center C-N oxidative addition or Hofmann elimination processes.     

Formation of complex organics from acetylene catalyzed by ionized benzene

We present direct evidence for low temperature associative charge transfer (ACT) reactions of acetylene onto the benzene cation that catalyze the conversion of acetylene molecules into polymerized cations and for high temperature addition/elimination reactions that lead to the generation of naphthalene-type ions. At low temperatures acetylene molecules bind noncovalently to the benzene cation, where partial charge transfer from the ion activates an acetylene molecule for addition polymerization with other associated acetylene molecules, thus amounting to catalytic cyclization/polymerization of the acetylene molecules. At high temperatures the barrier of the covalent addition of acetylene to the benzene cation to form a styrene-type ion is measured as 3.5 kcal/mol. The second acetylene addition followed by H elimination to form a naphthalene-type ion is calculated to be highly exothermic and without a barrier. These reactions can explain the formation of complex organics by gas phase ion-molecule reactions under a wide range of temperatures and pressures in astrochemical environments.     

Mechanism of beta-hydrogen elimination from square planar iridium(I) alkoxide complexes with labile dative ligands

Mechanistic studies were conducted on beta-hydrogen elimination from complexes of the general formula [Ir(CO)(PPh(3))(2)(OR)], which are square planar alkoxo complexes with labile ligands. The dependence of rate, isotope effect, and alkoxide racemization on phosphine concentration revealed unusually detailed information on the reaction pathway. The alkoxo complexes were remarkably stable, including those with a variety of electronically and sterically distinct groups at the beta-carbon. These complexes were much more stable than the corresponding alkyl complexes. Thermolysis of these complexes in the presence of PPh(3) yielded the iridium hydride [Ir(CO)(PPh(3))(3)H] and the corresponding aldehyde or ketone with rate constants that were affected little by the groups at the beta-carbon. The reactions were first order in iridium complexes. At low [PPh(3)], the reaction rate was nearly zero order in PPh(3), but reactions at high [PPh(3)] revealed an inverse dependence of reaction rate on PPh(3). The rate constants were similar in toluene, THF, and chlorobenzene. The y-intercept of a 1/k(obs) vs [PPh(3)] plot displayed a primary isotope effect, indicating that the y-intercept did not simply correspond to phosphine dissociation. These data and a dependence of alkoxide racemization on [PPh(3)] showed that the elementary beta-hydrogen elimination step was reversible. A mechanism involving reversible beta-hydrogen elimination followed by associative displacement of the coordinated ketone or aldehyde by PPh(3) was consistent with all of our data. This mechanism stands in contrast with the pathways proposed recently for alkoxide beta-hydrogen elimination involving direct elimination, protic catalysts, or binuclear mechanisms and shows that alkoxide elimination can follow pathways similar to those for beta-hydrogen elimination from alkyl complexes.     

Energetics and mechanism of the decomposition of trifluoromethanol

The thermal instability of alpha-fluoroalcohols is generally attributed to a unimolecular 1,2-elimination of HF, but the barrier to intramolecular HF elimination from CF3OH is predicted to be 45.1 +/- 2 kcal/mol. The thermochemical parameters of trifluoromethanol were calculated using coupled-cluster theory (CCSD(T)) extrapolated to the complete basis set limit. High barriers of 42.9, 43.1, and 45.0 kcal/mol were predicted for the unimolecular decompositions of CH2FOH, CHF2OH, and CF3OH, respectively. These barriers are lowered substantially if cyclic H-bonded dimers of CF3OH with complexation energies of approximately 5 kcal/mol are involved. A six-membered ring dimer has an energy barrier of 28.7 kcal/mol and an eight-membered dimer has an energy barrier of 32.9 kcal/mol. Complexes of CF3OH with HF lead to strong H-bonded dimers, trimers and tetramers with complexation energies of approximately 6, 11, and 16 kcal/mol, respectively. The dimer, CH3OH:HF, and the trimers, CF3OH:2HF and (CH3OH)2:HF, have decomposition energy barriers of 26.7, 20.3, and 22.8 kcal/mol, respectively. The tetramer (CH3OH:HF)2 gives rise to elimination of two HF molecules with a barrier of 32.5 kcal/mol. Either CF3OH or HF can act as catalysts for HF-elimination via an H-transfer relay. Because HF is one of the decomposition products, the decomposition reactions become autocatalytic. If the energies due to complexation for the CF3OH-HF adducts are not dissipated, the effective barriers to HF elimination are lowered from approximately 20 to approximately 9 kcal/mol, which reconciles the computational results with the experimentally observed stabilities.     

Identification of Epoxide Functionalities in Protonated Monofunctional Analytes by Using Ion/Molecule Reactions and Collision-Activated Dissociation in Different Ion Trap Tandem Mass Spectrometers

A mass spectrometric method has been delineated for the identification of the epoxide functionalities in unknown monofunctional analytes. This method utilizes gas-phase ion/molecule reactions of protonated analytes with neutral trimethyl borate (TMB) followed by collision-activated dissociation (CAD) in an ion trapping mass spectrometer (tested for a Fourier-transform ion cyclotron resonance and a linear quadrupole ion trap). The ion/molecule reaction involves proton transfer from the protonated analyte to TMB, followed by addition of the analyte to TMB and elimination of methanol. Based on literature, this reaction allows the general identification of oxygen-containing analytes. Vinyl and phenyl epoxides can be differentiated from other oxygen-containing analytes, including other epoxides, based on the loss of a second methanol molecule upon CAD of the addition/methanol elimination product. The only other analytes found to undergo this elimination are some amides but they also lose O = B-R (R = group bound to carbonyl), which allows their identification. On the other hand, other epoxides can be differentiated from vinyl and phenyl epoxides and from other monofunctional analytes based on the loss of (CH₃O)₂BOH or formation of protonated (CH₃O)₂BOH upon CAD of the addition/methanol elimination product. For propylene oxide and 2,3-dimethyloxirane, the (CH₃O)₂BOH fragment is more basic than the hydrocarbon fragment, and the diagnostic ion (CH₃O)₂BOH₂⁺ is formed. These reactions involve opening of the epoxide ring. The only other analytes found to undergo (CH₃O)₂BOH elimination are carboxylic acids, but they can be differentiated from the rest based on several published ion/molecule reaction methods. Similar results were obtained in the Fourier-transform ion cyclotron resonance and linear quadrupole ion trap mass spectrometer.     

Analysis by DSC of the drying and sintering processes of alkoxide-derived SiO2–ZrO2 gels

The drying and sintering processes of SiO₂–ZrO₂ alkoxide-derived gels have been studied by means of DSC technique. In the drying process, most part of water and alcohols are removed from the gels. For the SiO₂ gel such elimination occurs at the end of the drying process, however for the ZrO₂ gel this elimination occurs during the whole drying time. An intermediate behavior is observed for the binary system SiO₂–ZrO₂ gels. In the sintering process, the DSC technique allows to determine the elimination of water and alcohols retained within the structure (open or close pores) and the well-known hydroxyl condensation of silica gel between 700° and 800°C is also observed. The ZrO₂ gel shows the final hydroxyl condensation at the heating temperature of 600°C. For the binary SiO₂–ZrO₂ gels, the hydroxyl condensation has been associated to the activation energy needed for the dissociation of silica hydroxyls. This energy decreases with the ZrO₂ concentration in the gel resulting in a sintering treatment of 500°C leading to the entire hydroxyl condensation for the gel with 75% ZrO₂–25% SiO₂.

By studying the temperature of the DSC peaks, it is possible to know the temperature at which most part of water and alcohols are leaving the gel, and these results can be used in order to select the corresponding drying or sintering schedules for obtaining a well-fabricated material.     

Quantum chemical studies of azoles 4. A novel elimination–addition mechanism of tetrazole and 1,2,4-triazole electrophilic substitution

Thermodynamic parameters of the addition–elimination and elimination–addition electrophilic substitution reactions of 1H-tetrazole and 1,2,4-1H-triazole obtained from DFT B3LYP/ 6-31G(d,p) quantum chemical calculations with proton as model electrophile are compared. According to calculations, the elimination–addition reactions can proceed without preliminary formation of N-protonated azolium salts.     

Computational study of Rh(I)-Catalyzed Cycloaddition–Fragmentation of N-cyclopropylacrylamides

Rh-catalyzed cycloaddition–fragmentation of N-cyclopropylacrylamides is an effective method to directly obtain substituted azocanes. In this transformation, the challenging step is insertion of CO and alkene into the more hindered proximal cyclopropane CC bond while avoiding competitive less hindered proximal CC activation. Given the importance of this novel strategy, we performed a density functional theory study to clarify the catalytic mechanism. The calculations confirm that cleavage of the more hindered bond is more favorable than cleavage of the less hindered bond for Rh-catalyzed (7 + 1) cycloaddition of N-cyclopropylacrylamides. Comparison between Rh-catalyzed (3 + 1 + 2) and (7 + 1) cycloaddition shows that the coordination mode with different ligand plays a crucial role in enabling different CC cleavage. The main factors responsible for the occurrence of β-hydride elimination rather than CC reductive elimination are also discussed. The kinetic preference for β-hydride elimination can be attributed to the transition state of CC reductive elimination being more distorted and forming in a much more concerted fashion than that of β-hydride elimination. Additionally, C4H elimination is disfavored owing to weaker interaction energy compared with C7H elimination by analyzing using the distortion/interaction model.     

HCN消除反应机理的理论研究

采用密度泛函理论方法从HCN氧化和水解两个方面研究了HCN消除反应机理,并考虑了HCN的直接消除反应(途径Ⅰ和途径Ⅱ)和CuO上的HCN消除反应(途径Ⅲ和途径Ⅳ)。途径Ⅰ为HCN与2个O2分子生成CO2、NO和H原子;途径Ⅱ为HCN与1个O2分子和1个H2O分子生成 CO2和NH3;途径Ⅲ为CuO上HNCO水解为CO2和NH3;途径Ⅳ为CuO上HCN水解为CO和NH3。研究发现,途径III速控步骤的活化自由能垒为157.32 kJ/mol,比途径Ⅱ中HNCO水解降低12.34 kJ/mol;比途径Ⅳ降低了63.8 kJ/mol。可见,HNCO是HCN净化过程中的重要中间体,CuO的加入降低了反应能垒,促进了HCN消除。     

Hydrogen/deuterium exchange in gas phase reactions of anions with some alkyl phenyl ethers

The gas phase reactions of anions with methyl and ethyl phenyl ether have been studied by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. ¹⁸O-Labelling has shown that part of the reactions of OH^- with methyl phenyl ether proceed via ipso-substitution, the main reaction channel being S_N2 substitution. Deuterium labelling has shown that extensive inter- and intramolecular hydrogen/deuterium exchange can precede the final substitution reaction. Hydrogen atoms originating from the methoxy substituent are involved in this exchange process. The reactions of anions with ethyl phenyl ether proceed mainly via an elimination mechanism. Deuterium labelling has shown that in some cases hydrogen/deuterium exchange takes place prior to elimination.     

Enantiodivergence in alkylation of 1-(6-methoxynaphth-2-yl)ethyl acetate by potassium dimethyl malonate catalyzed by chiral palladium-DUPHOS complex

Alkylation of racemic 1-(6-methoxynaphth-2-yl)ethyl acetate by potassium dimethyl malonate catalyzed by a chiral palladium-DUPHOS complex afforded the substitution product with 87% ee, along with 6-methoxy-2-vinylnaphthalene that arose from an elimination process, in a 43/57 substitution/elimination ratio. The reaction performed on a mixture of quasi-enantiomeric substrates provided insight into the stereochemical course of the reaction, establishing that—for a given enantiomer of the catalyst, one enantiomer of the substrate afforded mainly the substitution product whereas the other enantiomer underwent elimination.     

Stereochemical preferences in 4-center syn-eliminations from gaseous ions

Concerted unimolecular eliminations from ionized sec-alkyl aryl ethers (ROAr (+*)) display a preference for producing double bonds with trans geometry. This preference can be assessed quantitatively, provided that a regioselective variant can be found. Expulsion of neutral alkenes via syn-elimination to give ionized ArOH does not exhibit a pronounced preference with regard to the direction of elimination. By contrast, ionized 2-hexyl p-trifluoromethylphenyl ether eliminates neutral ArOH regioselectively, giving ionized 2-hexenes rather than ionized 1-hexene. Vicinally monodeuterated 2-hexyl and 3-hexyl ethers were prepared as pure diastereomers. Metastable ion decompositions of their gaseous radical cations are compared over two different time windows. The regioselectivity for the 2-hexyl ether allows the geometric preference for the double bonds to be estimated based on the difference between the erythro and threo monodeuterated diastereomers ( trans/ cis = 2.0 for producing ionized 2-hexene from parent ions with the lowest internal energies). The 3-hexyl ethers and ionized 2- and 3-phenoxyoctanes also undergo stereoselective elimination but give experimental values that reflect their lack of regioselectivity. Examination of erythro/ threo combinations shows that GC/MS/MS has the ability to quantitate stereochemistry in mixtures containing both positional and stereoisomers.