Ligand-modulated palladium oxidation catalysis: mechanistic insights into aerobic alcohol oxidation with the Pd(OAc)(2)/pyridine catalyst system

Pd(OAc)(2):pyridine (1:4) is an efficient catalyst system for the oxidation of alcohols with molecular oxygen. A mechanistic study of this reaction reveals that pyridine promotes the aerobic oxidation of palladium(0) but inhibits the oxidation of alcohol by palladium(II). Kinetic results reveal that turnover-limiting substrate oxidation consists of (i) formation of a palladium(II)-alkoxide, (ii) pyridine dissociation, and (iii) beta-hydride elimination. These results provide a framework for the design and/or screening of more effective aerobic oxidation catalysts.     

Using mechanistic and computational studies to explain ligand effects in the palladium-catalyzed aerobic oxidation of alcohols

The experimental and computational mechanistic details of the Pd(OAc)(2)/TEA-catalyzed aerobic alcohol oxidation system are disclosed. Measurement of various kinetic isotope effects and the activation parameters as well as rate law derivation support rate-limiting deprotonation of the palladium-coordinated alcohol. Rate-limiting deprotonation of the alcohol is contrary to the majority of related kinetic studies for Pd-catalyzed aerobic oxidation of alcohols, which propose rate-limiting beta-hydride elimination. This difference in the rate-limiting step is supported by the computational model, which predicts the activation energy for deprotonation is 3 kcal/mol higher than the activation energy for beta-hydride elimination. The computational features of the similar Pd(OAc)(2)/pyridine system were also elucidated. Details of the study illustrate that the use of TEA results in an active catalyst that has only one ligand bound to the Pd, resulting in a significant lowering of the activation energy for beta-hydride elimination and, therefore, a catalyst that is active at room temperature.     

Mechanistic studies of Wacker-type intramolecular aerobic oxidative amination of alkenes catalyzed by Pd(OAc)2/pyridine

Wacker-type oxidative cyclization reactions have been the subject of extensive research for several decades, but few systematic mechanistic studies of these reactions have been reported. The present study features experimental and DFT computational studies of Pd(OAc)(2)/pyridine-catalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a Pd(II)-amidate-alkene chelate with release of 1 equiv of pyridine and AcOH from the catalyst center, (2) alkene insertion into a Pd-N bond, (3) reversible β-hydride elimination, (4) irreversible reductive elimination of AcOH, and (5) aerobic oxidation of palladium(0) to regenerate the active trans-Pd(OAc)(2)(py)(2) catalyst. Evidence is obtained for two energetically viable pathways for the key C-N bond-forming step, featuring a pyridine-ligated and a pyridine-dissociated Pd(II) species. Analysis of natural charges and bond lengths of the alkene-insertion transition state suggest that this reaction is best described as an intramolecular nucleophilic attack of the amidate ligand on the coordinated alkene.     

Elucidating the significance of beta-hydride elimination and the dynamic role of acid/base chemistry in a palladium-catalyzed aerobic oxidation of alcohols

The mechanistic details of aerobic alcohol oxidation with catalytic Pd(IiPr)(OAc)(2)(H(2)O) (IiPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) are disclosed. Under optimal conditions, beta-hydride elimination is rate-limiting supported by kinetic studies including a high primary kinetic isotope effect (KIE) value of 5.5 +/- 0.1 and a Hammett rho value of -0.48 +/- 0.04. On the basis of these studies, a late transition state is proposed for beta-hydride elimination, which is further corroborated by theoretical calculations using density functional theory. Additive acetic acid modulates the rates of both the alcohol oxidation sequence and regeneration of the Pd catalyst. With no additive [HOAc], turnover-limiting reprotonation of intermediate palladium peroxo is kinetically competitive with beta-hydride elimination, allowing for reversible oxygenation and decomposition of Pd(0). With additive [HOAc] (>2 mol %), reprotonation of the palladium peroxo is fast and beta-hydride elimination is the single rate-controlling step. This proposal is supported by an apparent decomposition pathway modulated by [HOAc], a change in alcohol concentration dependence, a lack of [O(2)] dependence at high [HOAc], and significant changes in the KIE values at different HOAc concentrations.     

Mechanism of Pd(OAc)2/DMSO-catalyzed aerobic alcohol oxidation: mass-transfer-limitation effects and catalyst decomposition pathways

Pd(OAc)(2) in DMSO is an effective catalyst for the aerobic oxidation of alcohols and numerous other organic substrates. Kinetic studies of the catalytic oxidation of primary and secondary benzylic alcohol substrates provide fundamental insights into the catalytic mechanism. In contrast to the conclusion reached in our earlier study (J. Am. Chem. Soc. 2002, 124, 766-767), we find that Pd(II)-mediated alcohol oxidation is the turnover-limiting step of the catalytic reaction. At elevated catalyst loading, however, the rate of catalytic turnover is limited by the dissolution of oxygen gas into solution. This mass-transfer rate is measured directly by using gas-uptake methods, and it correlates with the maximum rate observed during catalysis. Initial-rate studies were complemented by kinetic analysis of the full-reaction timecourses at different catalyst concentrations. Kinetic fits of these traces reveal the presence of unimolecular and bimolecular catalyst decomposition pathways that compete with productive catalytic turnover.     

Mechanistic study of alcohol oxidation by the Pd(OAc)(2)/O(2)/DMSO catalyst system and implications for the development of improved aerobic oxidation catalysts

The Pd(OAc)2/O2/DMSO catalyst system displays impressive versatility in the aerobic oxidation of organic substrates, ranging from alcohols to olefins. This report details mechanistic insights into these reactions. Dimethyl sulfoxide (DMSO) plays no redox role in the chemistry, and kinetic experiments identify the turnover-limiting step as DMSO-promoted oxidation of palladium(0) by molecular oxygen. The "chemical oxidase" pathway characterized for this catalyst system holds great promise for the design of new aerobic oxidation reactions.     

Unexpected roles of molecular sieves in palladium-catalyzed aerobic alcohol oxidation

Methods for palladium-catalyzed aerobic oxidation of alcohols often benefit from the presence of molecular sieves. This report explores the effect of molecular sieves on the Pd(OAc)2/pyridine and Pd(OAc)2/DMSO (DMSO = dimethyl sulfoxide) catalyst systems by performing kinetic studies of alcohol oxidation in the presence and absence of molecular sieves. Molecular sieves enhance the rate of the Pd(OAc)2/pyridine-catalyzed oxidation of alcohols, and the effect is attributed to the ability of molecular sieves to serve as a Br?nsted base. In contrast, no rate enhancement is observed for the Pd(OAc)2/DMSO-catalyzed reaction. Both catalyst systems exhibit improved catalyst stability in the presence of molecular sieves, manifested by higher catalytic turnover numbers. Control experiments indicate that neither of these beneficial effects is associated with the ability of molecular sieves to absorb water, a stoichiometric byproduct of these reactions. Finally, the use of simultaneous gas-uptake and in-situ IR spectroscopic studies reveal that molecular sieves inhibit the disproportionation of H2O2, an observation that contradicts a previous suggestion that the beneficial effect of molecular sieves may arise from their ability to promote H2O2 disproportionation.     

Structure of complexes formed by dissolution of palladium diacetate in methanol and chloroform. In situ NMR study

The behavior of palladium diacetate cyclic trimer [Pd(OAc)(2)](3) (1) upon its dissolution in methanol and wet chloroform was studied by (1)H and (13)C NMR including 2D-HSQC and 2D-DOSY techniques. Upon dissolution, trimer 1 reacts with methanol and is completely transformed first into the methoxo complex Pd(3)(μ-OMe)(OAc)(5) (2), which already at -18 °C undergoes a slow exchange of second bridging acetate ligand between the same palladium atoms to form the symmetric dimethoxo complex Pd(3)(μ-OMe)(2)(OAc)(4), the maximum relative concentration of which reaches 20-30 mol % of initial loading trimer 1. Along with the dimethoxo complex, both soluble and insoluble polynuclear palladium clusters are gradually formed at -18 °C, and their total amount reaches up to 60% of the starting Pd(2+) loading. The increase of temperature to 27 °C results in the reduction of palladium(II) to Pd metal by methanol, which is oxidized and transformed into formaldehyde hemiacetal and methyl formate. Upon dissolution in wet chloroform, trimer 1 is reversibly hydrolyzed to the hydroxo complex Pd(3)(μ-OH)(OAc)(5) (10) in ratio 1/10 ≈ 3/1. The temperature decrease and addition of acetic acid shift the equilibrium in this system toward trimer 1, and addition of water shifts it in the opposite direction. Addition of methanol to the equilibrium mixture of 1 and 10 results in the fast exchange of bridging acetate in trimer 1 by the μ-OMe group. Substitution of the μ-OH ligand by μ-OMe in 10 occurs in parallel but more slowly. Complex 2 formed in both cases is more stable in chloroform than in methanol.     

Palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates,iodides, and bromides to indanones and 2-cyclopentenones

Indanones and 2-cyclopentenones have been successfully prepared in good to excellent yields by the palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides, respectively. The best results are obtained by employing 10 mol % of Pd(OAc)(2), 2 equiv of pyridine, 1 equiv of n-Bu(4)NCl, 1 atm of CO, a reaction temperature of 100 degrees C, and DMF as the solvent. This carbonylative cyclization is particularly effective on substrates that contain a terminal olefin. The proposed mechanism for this annulation includes (1) Pd(OAc)(2) reduction to the active palladium(0) catalyst, (2) oxidative addition of the organic halide or triflate to Pd(0), (3) coordination and insertion of carbon monoxide to produce an acylpalladium intermediate, (4) acylpalladation of the neighboring carbon-carbon double bond, (5) reversible palladium beta-hydride elimination and re-addition to form a palladium enolate, and (6) protonation by H(2)O to produce the indanone or 2-cyclopentenone.     

Stoichiometric reactions of methylparathion with a palladium aryl oxime metallacycle

The reaction of [Pd(3)(OAc)(6)] with (E)-acetophenone oxime and pyridine in CHCl(3) under reflux affords the metallacycle [Pd(OAc)[C,N-(C(6)H(4)C(CH(3))=NOH)-2](py)] (1) as a yellow air-stable complex. The same reaction carried out at room temperature in the absence of pyridine affords the trinuclear oximato complex [Pd(mu-(E)-ON=C(CH(3))Ph)(mu-OAc)](3) (2), which can be converted into 1 upon heating in the presence of pyridine. As indicated by (1)H and (31)P NMR spectroscopy, complex 1 reacts with methylparathion in acetone-d(6)-D(2)O solutions to afford [Pd(SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2](py)] (3) and [Pd(mu-SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2]](2) (4) as well as free p-nitrophenol. Compounds 1-4 have been characterized by single-crystal X-ray analysis, NMR and EA. Compounds 1 and 3 are mononuclear complexes with the acetate and dimethylthiophosphate ligand, respectively, trans from the phenyl group. Compound 2 is a trinuclear complex whose structure can be derived from that of [Pd(3)(OAc)(6)] by replacing three of the acetate ligands on one side of Pd(3) plane by three N,O-coordinated oximate ligands. Complex 4 is a dinuclear complex in which the two square-planar palladium moieties are linked by the sulfur atoms of the bridging dimethylthiophosphate ligands.     

A smart palladium catalyst in ionic liquid for tandem processes

New catalytic systems based on in situ and preformed palladium nanoparticles in ionic liquids (characterised by TEM) starting from palladium acetate or dipalladiumtris(dibenzylideneacetone) have been applied in the synthesis of 4-phenylbutan-2-one (II), a model compound for the preparation of fragrances. Imidazolium-based ionic liquid containing a methyl hydrogenophosphonate anion leads to an efficient Pd-catalyzed tandem coupling/reduction process, taking advantage of the multi-role of this solvent (nanoparticles stabiliser, base, hydrogen transfer agent). The influence of the mono-phosphine ligands (1-3) on the catalyst has been evaluated, showing that the ligand-free palladium system turns into the most appropriate for the formation of II using Pd(OAc)(2) as precursor. Fine-tuning conditions involved in this multi-parameter process have led us to propose a plausible mechanism based on the hydrogen transfer coming from the methyl hydrogenophosphonate anion.     

Homeopathic ligand-free palladium as a catalyst in the heck reaction. A comparison with a palladacycle

[reaction: see text] Ligand-free Pd(OAc)(2) can be used as a catalyst in the Heck reaction of aryl bromides as long as the amount of catalyst is kept between 0.01 and 0.1 mol %. At higher concentrations palladium black forms and the reaction stops. The actual catalyst is monomeric. Palladacycles merely serve as a source of ligand-free palladium in Heck reactions of aryl bromides.     

A catalytic and mechanistic investigation of a PCP pincer palladium complex in the Stille reaction

In an improved procedure, the complex {2,6-bis[(diphenylphosphino)methyl]benzene}chloropalladium(II) (1) was synthesised as its THF adduct and the structure was determined by X-ray crystallography. The catalytic properties of the derivative {2,6-bis[(diphenylphosphino)methyl]benzene}(trifluoroacetato)palladium(II) (2) was investigated in the Stille reaction. Complex 2 proves to be an excellent catalyst for the C-C cross-coupling between trimethyl phenyl stannane and aryl bromides using a very low catalyst loading (0.1-0.0001%), giving high turnover numbers (TONs) up to 6.9 x 10(5). A kinetic investigation of the catalytic reaction suggests a heterogeneous colloidal palladium catalyst formed from the PCP Pd(II) pre-catalyst.     

Homogeneous palladium catalyst suppressing Pd black formation in air oxidation of alcohols

In homogeneous catalyst systems, there is the persistent problem that metal aggregation and precipitation cause catalyst decomposition and considerable loss of catalytic activity. Pd black formation is a typical example. Pd catalysts are known to easily aggregate and form Pd black, although they realize a wide variety of useful reactions in organic synthesis. In order to overcome this intrinsic problem of homogeneous Pd catalysis, we explored a new class of Pd catalyst by adopting aerobic oxidation of alcohols as a probe reaction. Herein we report a new catalyst system that suppresses the Pd black formation even under air and with a high substrate to catalyst molar ratio (S/C: more than 1000) in oxidation of alcohols. The novel pyridine derivatives having a 2,3,4,5-tetraphenylphenyl substituent and its higher dendritic unit at the 3-position of the pyridine ring were found to be excellent ligands with Pd(OAc)2 in the palladium-catalyzed air (balloon) oxidation of alcohols in toluene at 80 degrees C. Comparison with structurally related pyridine ligands revealed that introduction of the 2,3,4,5-tetraphenylphenyl substituent at the 3-position of pyridine ring effectively suppresses the Pd black formation, maintaining the catalytic activity for a long time to give aldehydes or ketones as products in high yields.     

Palladium-catalyzed benzylation of unprotected anthranilic acids with benzyl alcohols in water

Palladium-catalyzed benzylation of unprotected anthranilic acids with benzyl alcohols in the presence of Pd(OAc)(2) (5 mol %) and sodium diphenylphosphinobenzene-3-sulfonate (TPPMS, 10 mol %) in water at 120 °C for 16 h gave only dibenzylated anthranilic acids in good yields. Water may play important roles for the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol.     

Excited-state energy-transfer dynamics in self-assembled triads composed of two porphyrins and an intervening Bis(dipyrrinato)metal complex

The synthesis and characterization of various triads composed of a linear array of two zinc porphyrins joined via an intervening bis(dipyrrinato)metal(II) complex are reported. The preparation exploits the facile complexation of dipyrrins with divalent metal ions to give bis(dipyrrinato)metal(II) complexes [abbreviated (dp)(2)M]. Copper(II) and palladium(II) chelates of dipyrrins (available by oxidation of dipyrromethanes) were prepared in 50-80% yield. A one-flask synthesis of bis(dipyrrinato)zinc(II) complexes was developed by oxidation of a dipyrromethane with DDQ or p-chloranil in the presence of Zn(OAc)(2).2H(2)O in THF ( approximately 80% yield). Three routes were developed for preparing porphyrin-dipyrrins: (1). Suzuki coupling of a boronate-substituted zinc porphyrin (ZnP) and bis[5-(4-iodophenyl)dipyrrinato]Pd(II) to give the (ZnP-dp)(2)Pd triad (50% yield), followed by selective demetalation of the (dp)(2)Pd unit by treatment with 1,4-dithiothreitol under neutral conditions (71% yield); (2). oxidation of a porphyrin-dipyrromethane with p-chloranil in the presence of Zn(OAc)(2).2H(2)O followed by chromatography on silica gel (71% yield); and (3). condensation of a dipyrrin-dipyrromethane and a dipyrromethane-dicarbinol under InCl(3) catalysis followed by oxidation with DDQ (10-16% yield). Four triads of form (ZnP-dp)(2)Zn were prepared in 83-97% yield by treatment of a porphyrin-dipyrrin with Zn(OAc)(2).2H(2)O at room temperature. Free base dipyrrins typically absorb at 430-440 nm, while the bis(dipyrrinato)metal complexes absorb at 460-490 nm. The fluorescence spectra/yields and excited-state lifetimes of the (ZnP-dp)(2)Zn triad in toluene show (1). efficient energy transfer from the bis(dipyrrinato)zinc(II) chromophore to the zinc porphyrins (98.5% yield), and (2). little or no quenching of the resulting excited zinc porphyrin relative to the isolated chromophore. Taken together, these results indicate that bis(dipyrrinato)zinc(II) complexes can serve as self-assembling linkers that further function as secondary light-collection elements in porphyrin-based light-harvesting arrays.     

Facile Hydrolysis and Alcoholysis of Palladium Acetate

Palladium(II) acetate is readily converted into [Pd₃(μ²‐OH)(OAc)₅] ( 1 ) in the presence of water in a range of organic solvents and is also slowly converted in the solid state. Complex 1 can also be formed in nominally anhydrous solvents. Similarly, the analogous alkoxide complexes [Pd₃(μ²‐OR)(OAc)₅] ( 3 ) are easily formed in solutions of palladium(II) acetate containing a range of alcohols. An examination of a representative Wacker‐type oxidation shows that the Pd‐OH complex 1 and a related Pd‐oxo complex 4 can be excluded as potential catalytic intermediates in the absence of exogenous water.     

Experimental investigation on the mechanism of chelation-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition

A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)(2)) in copper(II)-mediated azide-alkyne cycloaddition (AAC) reactions. Fluorescence and (1)H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)(2) suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)(2) in mediating a 2-picolylazide-involved AAC reaction than the fully reduced Cu(OAc)(2). Finally, the discontinuous kinetic behavior that has been observed by us and others in copper(I/II)-mediated AAC reactions is explained by the likely catalyst disintegration during the course of a relatively slow reaction. Complementing the prior mechanistic conclusions drawn by other investigators, which primarily focus on the copper(I)/alkyne interactions, we emphasize the kinetic significance of copper(I/II)/azide interaction. This work not only provides a mechanism accounting for the fast Cu(OAc)(2)-mediated AAC reactions involving chelating azides, which has apparent practical implications, but suggests the significance of mixed-valency dinuclear copper species in catalytic reactions where two copper centers carry different functions.     

A versatile palladium catalyst system for Suzuki-Miyaura coupling of alkenyl tosylates and mesylates

A general and effective palladium system for Suzuki-Miyaura coupling of alkenyl electrophiles under mild reaction conditions is reported. With the Pd(OAc)(2)/CM-phos system, a variety of alkenyl tosylates are coupled well with ArB(OH)(2). Moreover, the first successful examples of using alkenyl mesylates in alkenylation are also described.     

钯配合物催化烯烃氧化合成酮类物质的研究进展

本文系统地评述了钯配合物催化烯烃氧化合成酮类物质的研究进展。综述了改进Wacker 类催化剂催化活性的几种方法。总结了烯烃氧化合成酮类物质反应的几种典型催化体系及其作用机理。着重介绍了Pd (Ⅱ) HPA (杂多酸)、Pd (Ⅱ) FePc (酞菁铁)、Pd (Ⅱ) HQ (氢醌) FePc、Pd (Ⅱ) HQHPA、Pd (Ⅱ) CuSO₄ HPA 等Wacker 类催化体系在烯烃氧化合成酮类物质中的应用; 对Pd (Ⅱ) LCoNO₂、PdCl₂(MeCN)₂ CuCl、Pd (OAc)₂ 吡啶、氟两相等非Wacker 类催化体系在烯烃氧化合成酮类物质中的应用也作了讨论。