- Structure-Based Design, Synthesis and Biological Evaluation of Bis-Tetrahydropyran Furan Acetogenin Mimics Targeting the Trypanosomatid F1 Component of ATP Synthase
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The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for the severely debilitating neglected Tropical diseases of African sleeping sickness, Chagas disease and leishmaniasis, respectively. As part of our ongoing programme exploring the potential of simplified analogues of the acetogenin chamuvarinin we identified the T. brucei FoF1-ATP synthase as a target of our earlier triazole analogue series. Using computational docking studies, we hypothesised that the central triazole heterocyclic spacer could be substituted for a central 2,5-substituted furan moiety, thus diversifying the chemical framework for the generation of compounds with greater potency and/or selectivity. Here we report the design, docking, synthesis and biological evaluation of new series of trypanocidal compounds and demonstrate their on-target inhibitory effects. Furthermore, the synthesis of furans by the modular coupling of alkyne- and aldehyde-THPs to bis-THP 1,4-alkyne diols followed by ruthenium/xantphos-catalysed heterocyclisation described here represents the most complex use of this method of heterocyclisation to date.
- Zacharova, Marija K.,Tulloch, Lindsay B.,Gould, Eoin R.,Fraser, Andrew L.,King, Elizabeth F.,Menzies, Stefanie K.,Smith, Terry K.,Florence, Gordon J.
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supporting information
p. 5434 - 5440
(2019/06/10)
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- Insight into the mechanism of decarbonylation of methanol by ruthenium complexes; a deuterium labelling study
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In the reaction of [RuHClP3] (P = PPh3) with NaOMe in methanol, the product is [RuH2(CO)P3]. Short reaction times show that the final product is formed through [RuH4P3] as the major interme
- Lorusso, Patrizia,Eastham, Graham R.,Cole-Hamilton, David J.
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p. 9411 - 9417
(2018/07/29)
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- Ring-expanded N-heterocyclic carbene complexes of ruthenium
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The six-membered N-heterocyclic carbene l,3-bis(2,4,6-trimethylphenyl)-3,4, 5,6-tetrahydropyrimidin2-ylidene (6-Mes) reacts with Ru(PPh3) 3(CO)HF to afford Ru(6-Mes)(PPh3)(CO)HF (1), which is converted to the five-coordinate C-H activated carbene complex Ru(6-Mes)'(PPh3)(CO)H (2) upon treatment with Et3SiH. The hydride chloride precursor Ru(PPh3)3(CO)HCl affords a mixture of products with 6-Mes, but reacts cleanly with 1,3-bis(isopropyl)-3,4, 5,6-tetrahydropyrimidin-2-ylidene (6-1Pr) to give the six-coordinate activated complex Ru(6-1Pr)'(PPh3)2(CO)H (3a), in which the hydride is trans to the methylene arm of the activated NHC. This complex isomerizes in solution with ΔH# and Delta;S# values of 98.2 ± 4.6 kJ mol-1 and 15.5 ± 14.5Jmol -1 K-1.The major product from the isomerization, 3b, in which the hydride ligand is trans to carbene, can be made directly by reaction of 6-1Pr with Ru(PPh3)3(CO)H2.
- Armstrong, Robert,Ecott, Christopher,Mas-Marza, Elena,Page, Mkhael J.,Mahon, Mary F.,Whittlesey, Michael K.
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p. 991 - 997
(2010/04/25)
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- A new oxidative addition of ruthenium(O) into an aryl halide bond and subsequent intermolecular C-H insertion
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Summary: An unprecedented oxidative insertion of the activated ruthenium complex Quot;Ru(CO)(PPh3)2" into aryl halide bonds enables a novel preparation of stable five-coordinate 16-electron d(6) o-aryl-Ru(II) complex Ru(CO)(p-C6
- Grounds, Helen,Anderson, James C.,Hayter, Barry,Blake, Alexander J.
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p. 5289 - 5292
(2010/01/29)
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- Catalytic hydrodefluorination of aromatic fluorocarbons by ruthenium N-heterocyclic carbene complexes
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The catalytic hydrodefluorination (HDF) of hexafluorobenzene, pentafluorobenzene, and pen- tafluoropyridine with alkylsilanes is catalyzed by the ruthenium N-heterocyclic carbene (NHC) complexes Ru(NHC)(PPh 3)2(CO)H2 (NHC = SIMes (1,3-bis(2,4,6-trimethylphenyl) imidazolin-2-ylidene) 13, SIPr (1,3- bis(2,6-diisopropylphenyl)imidazolin-2- ylidene) 14, IPr (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) 15, IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) 16). Catalytic activity follows the order 15 > 13 > 16 > 14, with 15 able to catalyze the HDF of C6F5H with Et3SiH with a turnover number of up to 200 and a turnover frequency of up to 0.86 h-1. The catalytic reactions reveal (i) a novel selectivity for substitution at the 2-position in C6F5H and C5F5N, (ii) formation of deuterated fluoroarene products when reactions are performed in C 6D6, or C6D5CD3, and (iii) a first-order dependence on [fluoroarene] and zero-order relationship with respect to [R3SiH]. Mechanisms are proposed for HDF of C 6F6 and C6F5H, the principal difference being that the latter occurs by initial C-H rather than C-F activation.
- Reade, Steven P.,Mahon, Mary F.,Whittlesey, Michael K.
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p. 1847 - 1861
(2009/08/07)
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- Ruthenium induced C-N bond activation of an N-heterocyclic carbene: Isolation of C- and N-bound tautomers
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C-N bond activation of the N-heterocyclic carbene 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene occurs with Ru(PPh3)3(CO)HCl to give the C-2 bound 1-isopropyl-4,5-dimethylimidazol-2-ylidene complex Ru(C-IiPrHMe2/sub
- Burling, Suzanne,Mahon, Mary F.,Powell, Rachael E.,Whittlesey, Michael K.,Williams, Jonathan M. J.
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p. 13702 - 13703
(2007/10/03)
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- Multifunctional ruthenium catalysts: A novel borohydride-stabilized polyhydride complex containing the basic, chelating diphosphine 1,4-bis(dicyclohexylphosphino)butane and its application to hydrogenation and Murai catalysis
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[RuCl2(dcypb)(CO)]2 2 (dcypb = 1,4-bis(dicyclohexylphosphino)butane) was prepared in high yield via phosphine exchange between dcypb and RuCl2(CO)PPh3)2(DMF) (1). Reaction of 2 with 8 equiv of KBHsBu3 affords [fac-RuH3(CO)(dcypb)]- (3), stabilized by interactions with a K+ counterion and an intact KBHsBu3 molecule in the third coordination sphere. Substantial ion pairing accounts for the stability and high hydrocarbon solubility of 3. Complex 3 effects reduction of benzophenone under unprecedentedly mild conditions, at 1 atm of H2 in refluxing 2-propanol. It is also active for ortho functionalization of benzophenone under 20 atm of ethylene. Stoichiometric experiments reveal facile formation of orthometalated RuH(CO)[OC(C6H4)(Ph)](dcypb) (5), an intermediate proposed in both types of catalysis. The catalytic activity of isolated 5 supports this hypothesis in the case of hydrogenation but not of Murai catalysis. The X-ray crystal structures of 3 and 5 are reported.
- Drouin, Samantha D.,Amoroso, Dino,Yap, Glenn P.A.,Fogg, Deryn E.
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p. 1042 - 1049
(2008/10/08)
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- Catalytic addition of ferrocenyl ketones to olefins with the aid of Ru(H)2(CO)(PPh3)3
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The catalytic addition reactions of ferrocenyl ketones with terminal olefins in the presence of Ru(H)2(CO)(PPh3)3 as catalyst have been studied. Benzoylferrocene reacts with triethoxyvinylsilane, styrene and vinylferrocene, respectively, to give 1:1 coupling products I-III in high yields. C-H bond cleavage takes place at the carbon atom of the benzene ring at the ortho position of the carbonyl group and C-C bond formation takes place at the terminal carbon atom of the olefins. 2-Furoylferrocene reacts with vinylferrocene to give a 1:1 coupling product IV and the C-H bond cleavage takes place at the carbon atom of the furan ring at the ortho position of the carbonyl group and the C-C bond formation takes place at the terminal carbon atom of vinylferrocene. The new products I-IV have been characterized by elemental analysis, 1H-NMR and MS. The X-ray crystal structure of IV has been determined.
- Du, Hongguang,Liu, Qun,Shi, Shujian,Zhang, Shiwei
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p. 127 - 131
(2007/10/03)
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- Synthesis, spectral and electrochemical studies of ruthenium(II)/(III) complexes of alicyclic β-ketamines
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A series of ruthenium(II)/(III) complexes of alicyclic β-ketamines derived from 2-formylcyclohexanone and 4-X-substituted anilines, HFCA-X (where H is an ionisable enolic hydrogen and X = H, Cl, Br, OMe and NO2), have been prepared and characterized by spectroscopic techniques. The IR spectral data suggest the coordination of enolic oxygen and imino nitrogen to ruthenium. Ruthenium(II) complexes are diamagnetic (low spin d6, S = 0) and in solutions show intense MLCT transition. Their redox behaviours have been studied by cyclic voltammetry. The solid state low temperature ESR spectra of Ru(III) complexes show a low spin symmetry.
- Prasanna,Srinivasan,Rajagopal,Athappan
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p. 426 - 429
(2007/10/03)
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- Proton transfer in aminocyclopentadienyl ruthenium hydride complexes
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A new ruthenium hydride complex of the aminocyclopentadienyl ligand (Cp-N)RuH(PPh3)2 (Cp-N = C5H4CH2CH2NMe2, 1) has been prepared and characterized by X-ray diffraction. Protonation of 1 with excess HPF6 leads to the dicationic derivative [(Cp-NH)RuH2(PPh3)2]-(PF6) 2 (2), in which both the metal and the amino substituent have been protonated. Addition of 1 equiv of HBF4·Et2O to 1 leads to the complex [(Cp-N)Ru(PPh3)2](BF4) (3), containing a chelating amino cyclopentadienyl ligand after elimination of H2. However, using (HNEt3)-(BPh4) or (HPBu3)(BPh4) as protonating agent, it is possible to form [(Cp-NH)RuH(PPh3)2]-(BPh4) (4), which was isolated as yellow crystals of 4·H2O upon addition of undistilled methanol and characterized by X-ray crystallographic analysis. A fluxional process exchanging the ammonium proton and the hydride without changing the thermodynamic state of the system could be established by 1H NMR, and activation energies of 11 kcal·mol-1 were calculated for 4·H2O and the product resulting from in situ addition Of [HNEt3][BPh4] to 1, whereas an activation energy of 10.1 kcal·mol-1 was found for the product resulting from in situ addition of [HPBu3][BPh4] to 1. A density functional study (B3PW91) was carried out, and the dihydrogen bond in the model system for 4 was calculated to be 1.545 A?, in excellent agreement with T1 measurements (1.52 A?). The proposed mechanism for the fluxional process does not involve a proton transfer within the dihydrogen bond.
- Ayllon, José A.,Sayers, Stephen F.,Sabo-Etienne, Sylviane,Donnadieu, Bruno,Chaudret, Bruno,Clot, Eric
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p. 3981 - 3990
(2008/10/08)
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- Reactivity of Ru(H2)(H)2(PPh3)3: Dimerization to form (PPh3)2(H)Ru(μ-H)3Ru(PPh3) 3 and decarbonylation of ethanol under mild conditions
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Loss of H2 from RuH4(PPh3)3 (1) leads to formation of RuH2(PPh3)3; this intermediate has been shown to dimerize with loss of a phosphine to form (PPh3)2(H)Ru(μ-H)3Ru(PPh3) 3 (3). Formation of RuH2(PPh3)3 in the presence of ethanol leads to decarbonylation of the alcohol and formation of RuH2(PPh3)3(CO) (7), under the mild conditions of nonbasic solutions at 25°C. Reaction of 1 with methanol, 1-propanol, or benzyl alcohol at 60°C also results in decarbonylation and formation of 7. The mechanisms of formation of these complexes are discussed.
- Van Der Sluys, Lori Stepan,Kubas, Gregory J.,Caulton, Kenneth G.
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p. 1033 - 1038
(2008/10/08)
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- METHANOL AS A HYDROGEN DONOR IN REACTIONS HOMOGENEOUSLY CATALYSED BY RUTHENIUM AND RHODIUM COMPLEXES
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Under suitable conditions methanol can act as a hydrogen donor towards organic substrates, especially for the reduction of ketones to alcohols.A variety of complexes of rhodium, iridium, ruthenium, and osmium have been shown to be active for this reaction; the highest activity observed so far is that of t-phosphine-ruthenium-chloride systems such as .In all the reactions the methanol is oxidised to methyl formate; some carbon dioxide is also formed.Cyclohexanone is reduced to cyclohexanol, methyl vinyl ketone and mesityl oxide to the corresponding saturated ketones, and 4-t-butylcyclohexanone to a 4/1 mixture of the trans and cis 4-t-butylcyclohexanols; aldehydes are reduced with more difficulty and cyclohexene is comparatively unreactive.Possible mechanisms for the reaction are discussed in the light of observations of changes in the catalyst precursors that take place during the rections.The reactions with methanol are also contrasted with those in wich ethanol is used as hydrogen donor.
- Smith, Thomas A.,Maitlis, Peter M.
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p. 385 - 396
(2007/10/02)
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- INDENYL COMPLEXES OF RUTHENIUM(II). CRYSTAL STRUCTURE OF 5-C9H7)>ClO4.1/2CH2Cl2
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The compound 5-C9H7)> (I) has been made in high yield by reaction of with indene and potassium hydroxide in ethanol and its reactions have been examined.Complex I reacts with appropriate nucleophiles to give the complexes 5-C9H7)> (X=H, CH3, I, SnCl3, C2Ph) and 5-C9H7)>.Heating of complex I with methanol in a sealed tube leads to the elimination of the indenyl group and decarbonylation of methanol.Cationic complexes of formulae 5-C9H7)>ClO4 (L=CH3CN, 2-ClC6H4CN, CH2=CHCN, 1,2-(CN)2C6H4, C2H4(CN)2, N2H4, CNBut, CO, C=CHPh, and C2H4) and 5-C9H7)>ClO4 (L-L=2,5-norbornadiene (nbd), tetrafluorobenzobarrelene (tfb), ethylenediamine (en), propylenediamine (pn), biimidazole (Hbim), 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)) are obtained by treatment of complex I with the appropriate ligand and sodium perchlorate in methanol.Reaction of the vinylideneruthenium complex 1-C=CHPh)(PPh3)2(η5-C9H7)>ClO4 with oxygen gives 5-C9H7)>ClO4.The structure of 5-C9H7)>ClO4.1/2CH2Cl2 has been determined by X-ray diffraction.The space group is P with lattice constants a 18.5513(14), b 12.9165(5), and c 9.6898(5) Angstroem, and α 80.942(5), β 104.998(7) and γ 111.130(4) deg.Final R and Rw factors are 0.039 and 0.043, respectively, for the 6836 observed data (3?(I) criterion).The metal is bonded to an indenyl group through the five-membered ring, and hexacoordination of the ruthenium atom is completed by two triphenylphosphine ligands and a carbonyl group.
- Oro, Luis A.,Ciriano, Miguel A.,Campo, Marina,Foces-Foces, Concepcion,Cano, Felix H.
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p. 117 - 132
(2007/10/02)
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- REGIOSELECTIVE C-O BOND CLEAVAGE OF ALLYLIC PHENYL CARBONATES PROMOTED BY GROUP 8 TRANSITION METAL HYDRIDO COMPLEXES
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Carbon-oxygen bonds in allylic phenyl carbonates are selectively cleaved by hydrido complexes of Co, Ru and Rh to give Co(OPh)L3, Ru(OPh)L2 and Rh(OPh)L3 with liberation of propylene and CO2.An intermediate complex RuH(O2COEt)L3 has been isolated in the reaction of RuH2(PPh3)4 with allyl ethyl carbonate.Reaction mechanisms are also discussed.
- Hayashi, Yoshinori,Komiya, Sanshiro,Yamamoto, Takakazu,Yamamoto, Akio
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p. 977 - 980
(2007/10/02)
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- C-O bond cleavage of esters promoted by RhH(PPh3)4 and RuH2(PPh3)4
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Reactions of RCOOCgH4X(R=CH9,C2H5: X=H,p.OCH3)indicating the reaction of with is first order with respect to the concentration of the remaining. The rate of the remaining rest-order rate constant,h, of the reaction at 90° C is expressed as κ.
- Yamamoto, Takakazu,Mlyashita, Satoshi,Naito, Yoshiyuki,Komiya, Sanshfro,Ito, Takashi,Yomamoto, Akio
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p. 808 - 812
(2008/10/08)
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- Selective Dimerization of Aldehydes to Esters Catalyzed by Hydridoruthenium Complexes
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RuH2(PPh3)4 and other hydridoruthenium complexes catalyze selective conversion of aldehydes into esters in high yields.The method is applicable to most aliphatic aldehydes as well as to aromatic aldehydes.The purity of aldehydes is critical for achieving high conversions, since the presence of carboxylic acid completely inhibits the reaction and alcohol and triphenylphosphine reduce the yields of esters.RuH2(PPh3)4 is converted into Ru(CO)3(PPh3)2 through the reaction indicating the occurrence of decarbonylation of aldehyde.A mechanism involving the acyl-H cleavageof aldehyde is proposed to account for the catalysis and formation of compounds accompanying the reaction.The mechanism is compared with an alternative one which comprises of consecutive insertions of two aldehyde molecules into Ru-H bond followed by β-hydrogen abstraction from an alkoxo intermediate formed.Addition of water changes the reaction course togive carboxylato carbonyl complexes Ru(OCOR)2(CO)m(PPh3)2 (m = 1 and 2).Cross esterification studies showed the reactivity order of RCHO as R = Et > Me > n-Pr > i-Pr >> Ph.
- Ito, Takashi,Horino, Hiroshi,Koshiro, Yoshitaka,Yamamoto, Akio
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p. 504 - 512
(2007/10/02)
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- PREPARATION OF OCTAHEDRAL, HYDRIDO-AQUO-RUTHENIUM(II) COMPLEXES, AND STRUCTURAL CHARACTERISATION OF HYDRIDOAQUODICARBONYLBIS(TRIPHENYLPHOSPHINE)RUTHENIUM(II) TETRAFLUOROBORATE
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Reaction of RuH2(CO)(PPh3)3 with tetrafluoroboric acid/water gives BF4.Carbonylation of the latter compound yields BF.In the Ir spectra of these compounds, splitting of the asymmetric BF4- stretching band indicated the possibility of a coordinated tetrafluoroborato ligand, but an X-ray study of BF4 shows that the BF4- is not coordinated to the metal, but is involved in a network of hydrogen bonds with the coordinated water molecule and the ethanol molecule of crystallisation.The crystal are monoclinic, space group P21 with Z = 2 in a unit cell of dimensions a = 9.3959(4), b = 22.695(1), c = 9.7878(3) Angstroem, β - 109.12(1) deg.The observed and calculated densities are 1.39 and 1.404 g cm-3 respectively.The structure was solved by conventional methods and refined using the full-matrix least-squares equations to final residuals R and Rw of 0.048 and 0.064 respectively.The ruthenium atom is in a distorted octahedral coordination geometry.The Ru-CO distances (1.83 and 1.97(2) Angstroem) differ significantly, with the longer bond situated trans to the hydrido ligand.The Ru-P bonds (2.329 and 2.416(5) Angstroem) are also significantly different, and the P-Ru-P angle is markedly non-linear at 165.1(2) deg.This asymmetry can be attributed to crystal packing forces.
- Boniface, Suzanne M.,Clark, George R.,Collins, Terrence J.,Roper, Warren R.
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p. 109 - 117
(2007/10/02)
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- THE KINETICS AND MECHANISM OF HOMOGENEOUS HYDROGEN TRANSFER FROM ALCOHOLS TO BENZYLIDENEACETONE CATALYZED BY DICHLOROTRIS(TRIPHENYLPHOSPHINE)RUTHENIUM(II)
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Dichlorotris(triphenylphosphine)ruthenium(II) catalyzes the hydrogen transfer from alcohols to olefins.Kinetic studies were carried out at 170-190 deg C using the ruthenium(II) complex as homogeneous catalyst, benzyl alcohol, diphenylcarbinol, methylphenylcarbinol and benzoin as the hydrogen donors, benzylideneacetone as the hydrogen acceptor, and dibenzyl ether as a solvent.The IR spectra and GLC were used to monitor the reaction and the isotope effects were determined in order to elucidate the role of the catalyst and the mechanism of hydrogen transfer.In the reaction mixture RuCl2(PPh3)3 is converted by the alcohols into RuH2(CO)(PPh3)3, which then hydrogenates benzylideneacetone.The kinetic data are compatible with the expression. reaction rate = kobs The rate-determining step of this reaction is considered to be the transfer of hydrogen from the alcohol to a ruthenium species.
- Speier, Gabor,Marko, Laszlo
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p. 253 - 262
(2007/10/02)
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- Reactions of Ruthenium Triphenylphosphine Complexes with Diazadienes. Part 1. Reactions of and and Disproportionation of a Hydridochloro-complex
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The reactions between and half or one equivalent of a diazadiene (dad) give respectively molecular and ionic binuclear triply chloro-bridged complexes, and Cl which can also be obtained as its BPh4 salt.The compound reacts with diazadienes to produce , which disproportionates in polar solvents to give a hydrido- and a dichloro-compound and reacts with water to give a chlorodihydroxo-bridged hydrido-species, .
- Chaudret, Bruno,Poilblanc, Rene
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p. 539 - 544
(2007/10/02)
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