- Nuances in Fundamental Suzuki-Miyaura Cross-Couplings Employing [Pd(PPh3)4]: Poor Reactivity of Aryl Iodides at Lower Temperatures
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We have explored fundamental Pd-catalyzed Csp2-Csp2 Suzuki-Miyaura cross-couplings of aryl iodides (Ar-I) employing "classical" Pd/PPh3 catalyst systems. Surprisingly, we observed particularly inefficient couplings of these ostensibly reactive electrophiles in a range of conventional solvent mixtures at lower temperatures (50 °C), which was in stark contrast to analogous reactions featuring the equivalent aryl bromides. This feature of well-established Pd/PPh3-mediated Suzuki-Miyaura reactions has received scant attention in the literature. Most significantly, our studies suggest that the inefficient coupling of aryl iodides at lower temperatures derives from the unexpectedly poor turnover of the key on-cycle intermediate trans-[Pd(PPh3)2(Ar)(I)] (or related PdII-I species) in the presence of PPh3.
- Ho, Curtis C.,Olding, Angus,Smith, Jason A.,Bissember, Alex C.
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- Pd(0)-catalyzed phosphorus-carbon bond formation. Mechanistic and synthetic studies on the role of the palladium sources and anionic additives
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Pd(PPh3)4, Pd(dba)2, Pd(OAc)2, and PdCl2, have been evaluated as possible Pd(0) sources for the palladium-catalyzed P-C bond formation via a cross-coupling of aryl halides with H-phosphonate diesters. It was found that the most efficient catalytic system can be generated from Pd(OAc)2 with a key role being played by Pd(II) and Pd(0) species with coordinated acetate ions. The reactivity of differently ligated Pd(II) complexes was determined, and 31P NMR spectroscopy studies were carried out to provide mechanistic interpretations for the observed differences between the catalytic systems.
- Kalek, Marcin,Stawinski, Jacek
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- Stabilization of bis(triphenylphosphine)palladium(0) by chloride ions. Electrochemical generation of highly reactive zerovalent palladium complexes
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"Pd0(PPh3)2" has been generated by electroreduction of Cl2Pd(PPh3)2 in the absence of PPh3.Its structure is consistent with xPd0(PPh3)2>nnx-, with values of x and/or n depending on the chloride ion
- Amatore, Christian,Azzabi, Mohamed,Jutand, Anny
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- Efficient acid fluoride synthesis via carbonylation of organic halides
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Palladium, platinum, cobalt, and rhodium triphenylphosphine complexes were found to catalyze the formation of acid fluorides via carbonylation of organic halides with fluoride salts.For palladium complex-catalyzed reactions, the use of cesium fluoride in polar solvents such as acetone and acetonitrile exhibited superior performance.The reaction took place even under an atmospheric pressure of carbon monoxide.The success of the acid fluoride synthesis is discussed in terms of the facility of oxidative addition of the starting material and the product.
- Sakakura, Toshiyasu,Chaisupakitsin, Malinee,Hayashi, Teruyuki,Tanaka, Masato
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- Pd(0)-Catalyzed Asymmetric Carbohalogenation: H-Bonding-Driven C(sp3)-Halogen Reductive Elimination under Mild Conditions
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Carbon-halogen reductive elimination is a conceptually novel elementary reaction. Its emergence broadens the horizons of transition-metal catalysis and provides new access to organohalides of versatile synthetic value. However, as the reverse process of f
- Chen, Xin,Zhao, Jixiao,Dong, Ming,Yang, Ninglei,Wang, Jiaoyang,Zhang, Yueqi,Liu, Kun,Tong, Xiaofeng
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p. 1924 - 1931
(2021/02/06)
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- Electrochemical Palladium-Catalyzed Oxidative Sonogashira Carbonylation of Arylhydrazines and Alkynes to Ynones
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Oxidative carbonylation using carbon monoxide has evolved as an attractive tool to valuable carbonyl-containing compounds, while mixing CO with a stoichiometric amount of a chemical oxidant especially oxygen is hazardous and limits its application in scale-up synthesis. By employing anodic oxidation, we developed an electrochemical palladium-catalyzed oxidative carbonylation of arylhydrazines with alkynes, which is regarded as an alternative supplement of the carbonylative Sonogashira reaction. Combining an undivided cell with constant current mode, oxygen-free conditions avoids the explosion hazard of CO. A diversity of ynones are efficiently obtained using accessible arylhydrazines and alkynes under copper-free conditions. A possible mechanism of the electrochemical Pd(0)/Pd(II) cycle is rationalized based upon cyclic voltammetry, kinetic studies, and intermediates experiments.
- Cao, Yue,Hu, Jingcheng,Lei, Aiwen,Li, Haoran,Shi, Renyi,Wu, Yong,Xu, Minghao,Yi, Hong,Zeng, Li
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supporting information
p. 12460 - 12466
(2021/08/24)
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- Palladium-Catalyzed Stereoselective Hydrodefluorination of Tetrasubstituted gem-Difluoroalkenes
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A highly stereoselective palladium(0)-catalyzed hydrodefluorination (HDF) of tetrasubstituted gem-difluoroalkenes is developed. By using catalytic Pd(PPh3)4 (2.5-5 mol percent) and hydrosilane Me2PhSiH, various trisubstituted terminal (E)-monofluoroalkenes can be synthesized with excellent E/Z selectivity (>99:1) and good functional group tolerability. The key stereocontrol should be exerted by an ester-directed C-F bond oxidative addition step in the catalytic cycle.
- Ma, Qiao,Liu, Caroline,Tsui, Gavin Chit
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supporting information
p. 5193 - 5197
(2020/07/04)
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- Stoichiometric Studies on the Carbonylative Trifluoromethylation of Aryl Pd(II) Complexes using TMSCF3 as the Trifluoromethyl Source
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We have performed a series of stoichiometric studies in order to identify viable steps for a hypothetical catalytic cycle for the palladium-mediated carbonylative coupling of an aryl bromide with TMSCF3. Our work revealed that benzoyl Pd(II) complexes bearing Xantphos or tBu3P as the phosphine ligands, which are generated from the corresponding PdII(Ph)Br complexes exposed to stoichiometric 13CO from 13COgen, were unable to undergo transmetalation and reductive elimination to trifluoroacetophenone. Instead, in the presence of base and additional CO, these organometallic complexes readily underwent reductive elimination to the acid fluoride. Attempts to determine whether the acid fluoride could represent an intermediate for acetophenone production were unrewarding. Only in the presence of a boronic ester did we observe some formation of the desired product, although the efficiency of transformation was still low. Finally, we investigated the reactivity of four phosphine-ligated PdII(Ph)CF3 complexes (Xantphos, DtBPF, tBu3P, and triphenylphosphine) with carbon monoxide. With the exception of the tBu3P-ligated complex, all other metal complexes led to the facile formation of trifluoroacetophenone. We also determined in the case of triphenylphosphine that CO insertion occurred into the Pd-Ar bond, as trapping of this complex with n-hexylamine led to the formation of n-hexylbenzamide.
- Daasbjerg, Kim,Domino, Katrine,Johansen, Martin B.,Skrydstrup, Troels
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supporting information
(2020/03/04)
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- The Difluoromethyl Group as a Masked Nucleophile: A Lewis Acid/Base Approach
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The difluoromethyl group (R-CF2H) imparts desirable pharmacokinetic properties to drug molecules and is commonly targeted as a terminal functional group that is not amenable to further modification. Deprotonation of widely available Ar-CF2
- Geri, Jacob B.,Wade Wolfe, Michael M.,Szymczak, Nathaniel K.
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supporting information
p. 9404 - 9408
(2018/08/09)
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- Real-Time Mass Spectrometric Investigations into the Mechanism of the Suzuki-Miyaura Reaction
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Real-time monitoring of the Suzuki-Miyaura reaction using mass spectrometry during sequential addition of the various reaction components suggests that a dynamic series of equilibria exist in these solutions. Depending on conditions, the boronic acid can
- Yunker, Lars P. E.,Ahmadi, Zohrab,Logan, Jessamyn R.,Wu, Wenzhao,Li, Tengfei,Martindale,Oliver, Allen G.,McIndoe, J. Scott
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supporting information
p. 4297 - 4308
(2018/11/23)
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- Efficient 11C-carbonylation of isolated aryl palladium complexes for PET: Application to challenging radiopharmaceutical synthesis
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We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with 11CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first 11C-carbonyl labeling of an approved PET tracer, [11C]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [11C]olaparib and [11C]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other 11C-labeling strategies.
- Andersen, Thomas L.,Friis, Stig D.,Audrain, Hlne,Nordeman, Patrik,Antoni, Gunnar,Skrydstrup, Troels
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supporting information
p. 1548 - 1555
(2015/03/05)
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- Mechanistic Insights in the Exchange of Arylthiolate Groups in Aryl(arylthiolato)palladium Complexes Supported by a Dippe Ligand
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Carbon-sulfur activation of phenyl p-tolyl sulfide by a mixture of [Pd(dippe)(μ-H)]2 (1a) and dinuclear Pd(0), [(μ-dippe)Pd]2 (1b) (dippe = 1,2-bis(diisopropylphosphino)ethane), to yield four carbon-sulfur activation products, (dippe)Pd(p-tolyl)(SPh) (3a), (dippe)Pd(Ph)(S-p-tolyl) (3b), (dippe)Pd(SPh)(Ph)(3c), and (dippe)Pd(p-tolyl)(S-p-tolyl) (3d), was investigated. The carbon-sulfur complexes 3a-3d were completely characterized by 1H, 31P, and 13C NMR spectroscopy, elemental analysis, and X-ray diffraction. Exchange interactions between arylthiolate groups in (dippe)Pd(Ar)(SAr′) (3a-3d) were investigated, leading to understanding the mechanism of interconversions among the complexes.
- Munjanja, Lloyd,Brennessel, William W.,Jones, William D.
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p. 4574 - 4580
(2015/10/06)
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- Distinguishing between pathways for transmetalation in Suzuki-Miyaura reactions
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We report a systematic study of the stoichiometric reactions of isolated arylpalladium hydroxo and halide complexes with arylboronic acids and aryltrihydroxyborates to evaluate the relative rates of the two reaction pathways commonly proposed to account for transmetalation in the Suzuki-Miyaura reaction. On the basis of the relative populations of the palladium and organoboron species generated under conditions common for the catalytic process and the observed rate constants for the stoichiometric reactions between the two classes of reaction components, we conclude that the reaction of a palladium hydroxo complex with boronic acid, not the reaction of a palladium halide complex with trihydroxyborate, accounts for transmetalation in catalytic Suzuki-Miyaura reactions conducted with weak base and aqueous solvent mixtures.
- Carrow, Brad P.,Hartwig, John F.
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p. 2116 - 2119
(2011/04/23)
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- Facile Ar-CF3 bond formation at Pd. strikingly different outcomes of reductive elimination from [(Ph3P)2Pd(CF 3)Ph] and [(Xantphos)Pd(CF3)Ph]
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Facile and highly selective perfluoroalkyl-aryl reductive elimination from a metal center (Pd) has been demonstrated for the first time. At temperatures as low as 50-80 °C, [(Xantphos)Pd(Ph)CF3] undergoes remarkably clean decomposition to produce CF3Ph in high yield and selectivity. In contrast, analogous trifluoromethylpalladium aryls stabilized by rigid cis-chelating ligands such as dppe are completely unreactive at temperatures up to 130-140 °C. Decomposition of [(Ph3P)2Pd(Ph)CF3] in the presence of PhI in benzene at 60 °C does not produce PhCF3 but rather leads to [(Ph3P)2Pd(Ph)I] and [Ph4P]+[(Ph3P)Pd(CF3)3]- in a 2:1 ratio with high selectivity. Copyright
- Grushin, Vladimir V.,Marshall, William J.
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p. 12644 - 12645
(2008/02/05)
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- The NMR study of the mechanism of alkene arylation with anhydrides of aromatic acids
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The main steps of the catalytic cycle of the alkene arylation reaction with the participation of anhydrides of aromatic acids as arylation agents were studied by 31P NMR spectroscopy. The catalytic cycle of the reaction included the steps of ox
- Shmidt,Smirnov
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p. 195 - 198
(2008/10/08)
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- Rate and mechanism of the oxidative addition of benzoic anhydride to palladium(O) complexes in DMF
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The rate constant of the oxidative addition of the benzoic anhydride (PhCO)2O to [Pd0(PPh3)4] has been determined in DMF and compared to that of phenyl halides and phenyl triflate. The following reactivity order has been established: PhI >> (PhCO)2O > PhOTf > PhBr. The oxidative addition of (PhCO)2O proceeds by activation of one C-O bond. Two acyl-PdII complexes are formed: a neutral complex trans-[(PhCO)Pd(OCOPh)(PPh3)2] and a cationic complex trans-[(PhCO)PdS(PPh3)2]+ (S = DMF) showing that the decarbonylation process is highly endergonic. The exchange of PPh3 by the bidentate ligand dppp does not favor the decarbonylation process.
- Jutand, Anny,Negri, Serge,De Vries, Johannes G.
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p. 1711 - 1717
(2007/10/03)
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- Reactivity of [Pd3(μ-OAc)3(μ,η2-MeSCHCO 2Et-C,S)3] in the presence of triphenylphosphine: A model of the early steps of the Pd/PR3-catalysed Heck reaction
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The stable complex [Pd(η1-OAc)(η2-MeSCHCO2Et-C,S)(PPh 3)] (2) is readily formed by addition of triphenylphosphine to [Pd3(μ-OAc)3(μ,η2-MeSCHCO 2Et-C,S)3] (1:1 P:Pd) in acetone. It crystallizes in the monoclinic space group C2/c, with Z=8, a=145.08(2), b=109.82(1), c=306.33(3) pm and β=96.3(1)°, R(F)=0.026, Rw (F2)=0.0765. The coordination of a second triphenylphosphine to the palladium atom leads to [Pd(η1-OAc){CH(SMe)CO2Et}(PPh3) 2] (3). Whereas 2 appears to be remarkably stable, 3, after a slow reductive elimination, evolves mainly to [Pd(η2-MeSCHCO2Et-C,S)(PPh3) 2]-. Zero-valent palladium species can also be generated by electrochemical reduction of 3. The rate constant for the oxidative addition of iodobenzene to the electrogenerated palladium(0) species has been estimated.
- Basato, Marino,Sesto, Barbara,Zecca, Marco,Valle, Giovanni,Antonello, Sabrina,Maran, Flavio
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p. 201 - 210
(2007/10/03)
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- Carbon-sulfur bond-forming reductive elimination involving sp-, sp2-, and sp3-hybridized carbon. Mechanism, steric effects, and electronic effects on sulfide formation
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Palladium thiolato complexes [(L)Pd(R)(SR')], within which L is a chelating ligand such as DPPE, DPPP, DPPBz, DPPF, or TRANSPHOS, R is a methyl, alkenyl, aryl, or alkynyl ligand, and R' is an aryl or alkyl group, were synthesized by substitution or proton-transfer reactions. All of these thiolato complexes were found to undergo carbon-sulfur bond-forming inductive elimination in high yields to form dialkyl sulfides, diaryl sulfides, alkyl aryl sulfides, alkyl alkenyl sulfides, and alkyl alkynyl sulfides. Reductive eliminations forming alkenyl alkyl sulfides and aryl alkyl sulfides were the fastest. Eliminations of alkynyl alkyl sulfides were slower, and elimination of dialkyl sulfide was the slowest. Thus the relative rates for sulfide elimination as a function of the hybridization of the palladium-bound carbon follow the trend sp2 > sp >> sp3. Rates of reductive elimination were faster for cis-chelating phosphine ligands with larger bite angles. Kinetic studies, along with results from radical trapping reactions, analysis of solvent effects; and analysis of complexes with chelating phosphines of varying rigidity, were conducted with [Pd(L)(S-tert-butyl)(Ar)] and [Pd(L)(S- tert-butyl)(Me)]. Carbon-sulfur bond-forming reductive eliminations involving both saturated and unsaturated hydrocarbyl groups proceed by an intramolecular, concerted mechanism. Systematic changes in the electronic properties of the thiolate and aryl groups showed that reductive elimination is the fastest for electron deficient aryl groups and electron rich arenethiolates, suggesting that the reaction follows a mechanism in which the thiolate acts as a nucleophile and the aryl group an electrophile. Studies with thiolate ligands and hydrocarbyl ligands of varying steric demands favor a migration mechanism involving coordination of the hydrocarbyl ligand in the transition state.
- Mann, Grace,Baranano, David,Hartwig, John F.,Rheingold, Arnold L.,Guzei, Ilia A.
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p. 9205 - 9219
(2007/10/03)
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- Unexpected bell-shaped effect of the ligand on the rate of the oxidative addition to palladium(0) complexes generated in situ from mixtures of Pd(dba)2 and para-substituted triarylphosphines
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As with PPh3, mixtures of Pd(dba)2 and n L (L = para-Z-substituted triphenylphosphines, n ≥ 2) in DMF lead to the formation of Pd(dba)L2 and PdL3 in equilibrium with PdL2. The equilibrium between Pd(dba)L2 and PdL3 is more in favor of PdL3 when the phosphine is less electron rich. In other words, the exchange of the dba ligand by a phosphine from Pd(dba)L2 to form PdL3 is more favored when the phosphine is less electron rich. The less ligated complex PdL2 is the reactive species in the oxidative addition with phenyl iodide. It was therefore expected that the rate of the oxidative addition would increase when the phosphine is more electron rich. However, surprisingly, when the palladium(0) complex is generated from mixtures of Pd(dba)2 and n L (n ≥ 2), the oxidative addition does not follow a linear Hammett correlation and the reactivity of the palladium(0) complex exhibits a maximum value. This is due to two antagonist effects. Indeed, the overall reactivity in the oxidative addition is governed by two factors: the intrinsic reactivity of PdL2 and its concentration. When the phosphine becomes more electron rich, the complex PdL2 becomes more nucleophilic and its intrinsic reactivity in the oxidative addition increases. However, when the phosphine becomes more electron rich, the concentration of PdL2 decreases because the equilibrium between the palladium(0) complexes becomes more in favor of Pd(dba)L2. These results emphasize the crucial role of the dba ligand on the reactivity of palladium(0) complexes generated in situ in mixtures of Pd(dba)2 and phosphines.
- Amatore, Christian,Jutand, Anny,Meyer, Gilbert
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- Fluoride-induced reduction of palladium(II) and platinum(II) phosphine complexes
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A novel redox reaction involving fluoride and phosphine complexes of palladium(II) is reported. The scope of this reaction has been investigated using the ligands PPh3, Ph2P(CH2)nPPh2 (n = 1-4), Ph2PCH2C(CH3)2CH2PPh 2, Ph2PCH3, and P(CH2CH2CN)3; several solvents including DMSO, pyridine, acetonitrile, and THF; and either n-Bu4NF·3H2O or KF/18-crown-6 as the fluoride source. The reduction products are palladium(0) phosphine complexes for which this reaction offers a convenient synthetic route. 31P and 19F NMR spectra permitted identification of the initial oxidation products as difluorophosphoranes (R3PF2), which subsequently hydrolyzed, forming phosphine oxides if a hydrated fluoride source is used. Results implicating a fluoride-induced redox reaction in the thermal decomposition of [(Ph3P)3PdCl]BF4 to yield [Pd3Cl(PPh2)2(PPh3) 3]BF4 are also presented. Preliminary results indicate that platinum complexes also undergo this reaction, but nickel complexes yield NiF2. The X-ray parameters for Pd(dppp)2 (dppp = 1,3-bis(diphenyphosphino)propane) are: monoclinic, space group C2/c (No. 15), a = 18.396 (2) A?, b = 13.290 (1) A?, c = 20.186 (2) A?, β = 109.383 (5)°, and Z = 4.
- Mason,Verkade
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p. 2212 - 2220
(2008/10/08)
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- Palladium-Catalyzed Germylation of Organic Halides with a Digermane. Unexpected Formation of Germylene-Insertion Type Products
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Organic halides (RX) underwent dehalogenative germylation and germylene insertion type reactions with ClMe2GeGeMe2Cl in the presence of Pd(PPh3)4 as catalyst to give RGeMe2Cl and RGeMe2X respectively.
- Reddy, Prabhakar N.,Hayashi, Teruyuki,Tanaka, Masato
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p. 677 - 680
(2007/10/02)
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- KINETICS OF OXIDATIVE ADDITION OF ZEROVALENT PALLADIUM TO AROMATIC IODIDES
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The kinetic of oxidative addition of zerovalent palladium to aromatic iodides in tetrahydrofuran in the presence of the ligand triphenylphosphine have been studied by amperometry on the oxidation wave of palladium.The reaction is first order in aromatic iodide and first order in palladium and the rate constant is inversely proportional to the free ligand concentration.The reactive palladium intermediate is assumed to be Pd2.This assumption is compatible with the observed activation parameters ΔH(excit.) = +77 kJ mol-1; ΔS(excit.) = 13 J mol-1 K-1.With substituted aromatic iodides, the rate constants give a linear Hammett relationship with ρ = +2.The suggested mechanism can be regarded as related to an aromatic nucleophilic substitution with some assistance from halogen-palladium interaction.
- Fauvarque, Jean-Francois,Pflueger, Fernando,Troupel, Michel
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p. 419 - 427
(2007/10/02)
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