Homogeneous Palladium Catalysts Research Articles

Palladium‐Catalyzed Hydroxycarbonylation of Diisobutene: Systematic Optimization by Central Composite Design

AbstractThe selection of suitable catalysts and reaction conditions are key elements for efficient process development. In this work, stability studies of homogeneous palladium catalysts used for the hydroxycarbonylation of olefins to aliphatic carboxylic acids are presented. Based on this, the hydroxycarbonylation of diisobutene, which represents an industrially relevant mixture of olefins, was investigated and optimized by means of central composite design with respect to the yield of the target product 3,5,5‐trimethylhexanoic acid. The modeling succeeds with high accuracy and allows to gain information about interactions between different factors in the reaction system. This allows a more accurate prediction of the reaction behavior and permits easier future scale‐up of such processes.

Synthesis of 2-Alkylaryl and Furanyl Acetates by Palladium Catalysed Carbonylation of Alcohols

The one-pot alkoxycarbonylation of halo-free alkylaryl and furanyl alcohols represents a sustainable alternative for the synthesis of alkylaryl and furanyl acetates. In this paper, the reaction between benzyl alcohol, chosen as a model substrate, CH3OH and CO was tested in the presence of a homogeneous palladium catalyst, an activator (isopropenyl acetate (IPAc) or dimethyl carbonate (DMC)) and a base (Cs2CO3). The influence of various reaction parameters such as the CO pressure, ligand and palladium precursor employed, mmol% catalyst load, temperature and time were investigated. The results demonstrate that decreasing the CO pressure from 50 bar to 5 bar at 130 °C for 18 h increases yields in benzyl acetate from 36% to over 98%. Further experiments were performed in the presence of piperonyl and furfuryl alcohol, interesting substrates employed for the synthesis of various fine chemicals. Moreover, furfuryl alcohol is a lignocellulosic-derived building block employed for the synthesis of functionalized furans such as 2-alkylfurfuryl acetates. Both the alcohols were successfully transformed in the corresponding acetate (yields above 96%) in rather mild reaction conditions (5–0.01 mol% catalyst, 5–2 bar CO pressure, 130 °C, 4–18h), demonstrating that the alkoxycarbonylation of alcohols represents a promising sustainable alternative to more impactful industrial practices adopted to date for the synthesis of alkylaryl and furfuryl acetates.

Reductive Carbonylation of Nitroarenes Using a Heterogenized Phen-Pd Catalyst.

The reductive carbonylation of nitroarenes in the presence of MeOH and CO(g) is one of the interesting alternative routes without utilizing toxic phosgene and corrosive HCl generation for the synthesis of industrially useful carbamate compounds that serve as important intermediates for polyurethane production. Since homogeneous palladium catalysts supported by phen (phen = 1,10-phenanthroline) are known to be effective for this catalysis, the heterogenized Pd catalyst was developed using the phen-containing solid support. In this study, we report the synthesis of a phen-based heterogeneous Pd catalyst, Pd@phen-POP, which involves the solvent knitting of a phen scaffold via the Lewis-acid-catalyzed Friedel-Crafts reaction using dichloromethane as a source for linker in the presence of AlCl3 as a catalyst. The resulting solid material has been thoroughly characterized by various physical methods revealing high porosity and surface area. Similar to the homogeneous pallidum catalyst, this heterogeneous catalyst shows efficient reductive carbonylation of various nitroarenes. The catalytic reaction using nitrobenzene as a model compound presents a high turnover number (TON = 530) and a reasonable turnover frequency (TOF = 45 h-1), with a high selectivity (92%) for the carbamate formation. According to the recycling study, the heterogeneous catalyst is recyclable and retains ∼90% of the original reactivity in each cycle.

Tritiation tricks with thianthrenium salts

To study how drugs and drug candidates behave in biological systems, scientists often replace a hydrogen atom in a compound of interest with an atom of the isotope tritium, which acts as a radioactive beacon. Chemists led by Tobias Ritter at the Max Planck Institute for Kohlenforschung report a new tritium-installation method that sidesteps challenges associated with other methods for tritiation ( Nature 2021, DOI: 10.1038/s41586-021-04007-y ). The reaction capitalizes on the reactivity of thianthrenium salts, which Ritter’s team reported in 2019 . Chemists can selectively place thianthrenium salts in the para position of aromatic groups. The thianthrenium group can then be replaced with tritium via hydrogenolysis using a homogeneous palladium catalyst and tritium gas. Although chemists have previously used hydrogenolysis to place tritium in molecules, they typically relied on heterogeneous catalysts—such as palladium on a carbon support—to do so. Heterogeneous catalysts tend to be less selective than homogeneous catalysts

Tritiation of aryl thianthrenium salts with a molecular palladium catalyst

Tritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding and receptor occupancy studies1. Tritium gas is the preferred source of tritium for the preparation of labelled molecules because it is available in high isotopic purity2. The introduction of tritium labels from tritium gas is commonly achieved by heterogeneous transition-metal-catalysed tritiation of aryl (pseudo)halides. However, heterogeneous catalysts such as palladium supported on carbon operate through a reaction mechanism that also results in the reduction of other functional groups that are prominently featured in pharmaceuticals3. Homogeneous palladium catalysts can react chemoselectively with aryl (pseudo)halides but have not been used for hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen4. Here we report a homogenous hydrogenolysis reaction with a well defined, molecular palladium catalyst. We show how the thianthrene leaving group—which can be introduced selectively into pharmaceuticals by late-stage C–H functionalization5—differs in its coordinating ability to relevant palladium(II) catalysts from conventional leaving groups to enable the previously unrealized catalysis with dihydrogen. This distinct reactivity combined with the chemoselectivity of a well defined molecular palladium catalyst enables the tritiation of small-molecule pharmaceuticals that contain functionality that may otherwise not be tolerated by heterogeneous catalysts. The tritiation reaction does not require an inert atmosphere or dry conditions and is therefore practical and robust to execute, and could have an immediate impact in the discovery and development of pharmaceuticals.

Recent Advances of Pd/C-Catalyzed Reactions

The Pd/C-catalyzed reactions, including reduction reactions and cross-coupling reactions, play an irreplaceable role in modern organic synthesis. Compared to the homogeneous palladium catalyst system, the heterogeneous Pd/C catalyst system offers an alternative protocol that has particular advantages and applications. Herein, a review on Pd/C-catalyzed reactions is presented. Both the advances in Pd/C-catalyzed methodologies and the application of Pd/C-catalysis in total synthesis are covered in this review.

Catalytic Liquefaction of Kraft Lignin with Solvothermal Approach

Lignin is a natural biopolymer present in lignocellulosic biomass. During paper pulp production with the Kraft process, it is solubilized and degraded in Kraft lignin and then burned to recover energy. In this paper, the solvolysis of Kraft lignin was studied in water and in water/alcohol mixtures to produce oligomers and monomers of interest, at mild temperatures (200–275 °C) under inert atmosphere. It was found that the presence of alcohol and the type of alcohol (methanol, ethanol, isopropanol) greatly influenced the amount of oligomers and monomers formed from lignin, reaching a maximum of 48 mg·glignin−1 of monomers with isopropanol as a co-solvent. The impact of the addition of various solid catalysts composed of a metal phase (Pd, Pt or Ru) supported on an oxide (Al2O3, TiO2, ZrO2) was investigated. In water, the yield in monomers was enhanced by the presence of a catalyst and particularly by Pd/ZrO2. However, with an alcoholic co-solvent, the catalyst only enhanced the formation of oligomers. Detailed characterizations of the products with FTIR, 31P-NMR, 1H-NMR and HSQC NMR were performed to elucidate the chemical transformations occurring during solvolysis. The nature of the active catalytic specie was also investigated by testing homogeneous palladium catalysts.

Strategies for sustainable palladium catalysis

• Overview of the current state of the art for sustainable palladium catalysis. • Critical survey of the recovery of palladium catalysts from secondary waste sources. • Summary of the design and scope of palladium catalysts employed at low-loadings. • Discussion of the design and scope of reusable, homogeneous palladium catalysts. • Comparison of the various approaches to sustainable palladium catalysis. Palladium is established both as an indispensable metal in modern synthetic chemistry and as a key component in catalytic converters and electronic equipment. The unrelenting demand for this metal increases both the financial and environmental cost, through mining, of this metal, rendering consumption unsustainable in its current form. This review provides a critical survey of the main approaches being pursued to address this issue, including low-loading catalysis, recyclable catalysts and the use of palladium recovered from secondary sources. The literature discussed herein reveals that catalysts that operate at low loadings are an attractive, sustainable option for many transformations, even when compared to catalyst systems that can be reused multiple times. Both low-loading and reusable catalysts depend on a finite natural supply of palladium, making the development of catalysts based on metal recovered from end-of-life materials (urban mining) a promising field of research. The way in which low-loading is achieved in different catalyst designs influences the choice of reaction temperature and solvent, which has additional environmental implications. Such factors are discussed for a wide range of systems alongside reaction and substrate scope, supported by extensive supplementary information . The survey aims to provide an insight into the relative merits of the approaches being explored and how the field of palladium-based catalysis might progress towards more sustainable use of this critical metal.

Efficient Heterogeneous Palladium Catalysts in Oxidative Cascade Reactions.

ConspectusPalladium-catalyzed oxidations involving cascade processes provide a versatile platform for streamlined conversion of simple feedstocks into functional molecules with high atom and step economy. However, the achievement of high palladium efficiency and selectivity in Pd-catalyzed oxidative cascade reactions is still challenging in many cases, as a result of the aggregation of active palladium species to Pd black and the possible side reactions during each bond-forming step. The two current solutions for addressing these issues are either to utilize oxidant-stable ligands or to use electron transfer mediators (ETMs). The former solution, which includes the use of amines, pyridines, sulfoxides, and carbene derivatives, inhibits aggregation of Pd0 during the catalytic cycle, while the latter solution facilitates reoxidation of Pd0 to PdII to improve the activity and selectivity. Following our long-standing interest in Pd-catalyzed oxidations, very recently we developed heterogeneous catalysts to resolve the issues mentioned above in oxidative cascade reactions. The heterogeneous palladium catalysts (Pd-AmP-MCF or Pd-AmP-CNC) comprise palladium nanoclusters (1–2 nm) immobilized on amino-functionalized siliceous mesocellular foam (MCF) or on crystalline nanocellulose (CNC), exhibiting high activity, selectivity as well as excellent recycling ability.In this Account, we will discuss the synthesis and characterizations of the heterogeneous palladium catalysts, as well as their catalytic behaviors, and the mechanisms involved in their reactions. An important aspect of these catalysts in oxidation reactions is the generation of active Pd(II) species within the heterogeneous phase. Typical oxidative cascade reactions of our recent research on this topic include oxidative carbocyclization-carbonylation, oxidative carbocyclization-borylation, oxidative alkynylation-cyclization, oxidative carbonylation-cyclization, and oxidative carbocyclization-alkynylation. These reactions provide access to important compounds attractive in medicinal chemistry and functional materials, such as γ-lactone/γ-lactam-based poly rings, cyclobutenols, highly substituted furans, and oxaboroles. During these processes, the heterogeneous catalysts exhibited much higher turnover numbers (TONs) than their homogeneous counterparts (e.g., Pd(OAc)2) as well as unique selectivity that cannot be achieved by homogeneous palladium catalysts. The origin of the high efficiency and unique selectivity of the heterogeneous catalysts was also investigated. Asymmetric syntheses for the construction of optically pure compounds were realized based on the excellent selectivity in these heterogeneous processes. Kinetic studies revealed that the rate and yield of the reactions were essentially maintained during recycling, which demonstrates that Pd-AmP-MCF and Pd-AmP-CNC are robust and highly active in these oxidative cascade reactions. In addition, inductively coupled plasma optical emisson spectroscopy (ICP-OES) analysis and hot filtration test suggest that these processes most likely proceed via a heterogeneous pathway.Recent progress in our group has shown that the activity of Pd-AmP-MCF and Pd-AmP-CNC could be improved even further by the addition of Ag+ to generate cationic Pd(II). Furthermore, intriguing solvent effects were observed in a Pd-AmP-MCF-catalyzed oxidative cascade process, and solvent-controlled chemoselective transformations were developed based on this property of the catalyst. The heterogeneous strategy of this Account provides solutions to palladium deactivation and selectivity issues in Pd(II)-catalyzed oxidative cascade reactions and enables efficient catalyst recycling, which will open up new opportunities in oxidative cascade reactions.

Separation of homogeneous palladium catalysts from pharmaceutical industry wastewater by using synergistic recovery phase via HFSLM system

Separation of homogeneous palladium catalysts from pharmaceutical industry wastewater by using synergistic recovery phase via hollow fiber supported liquid membrane (HFSLM) system is presented. HFSLM impregnated with N-methyl-N,N,N-trioctylammonium chloride (Aliquat 336) as the extractant dissolved in cyclohexane. The influence of various chemical parameters, including the concentration of extractant and recovery phases as well as recovery selector concentration in recovery phase, were also studied. A mixture of hydrochloric acid and thiourea was used as synergistic recovery phase. The highest percentage of extraction and recovery was 99.95% and 88.12%, respectively. Furthermore, the kinetics of recovery reaction was studied to provide reaction order, reaction rate constant, equilibrium constant and distribution ratio.

Direct Arylations of Heteroarenes with Benzenesulfonyl Chlorides Using Pd/C Catalyst

The reactivity of heteroaromatics in direct arylation with benzenesulfonyl chlorides using 10 % Pd/C as catalyst was explored. With (benzo)thiophenes, (benzo)furans, pyrroles and selenophenes, high yields in arylated heteroarenes were obtained. These arylations were performed using only 5 mol‐% Pd/C and Li2CO3 as inexpensive base. The regioselectivities are similar to those observed with homogeneous palladium catalysts. Better yields were obtained with electron‐deficient benzenesulfonyl chlorides than with the electron‐rich ones. Notably, useful substituents such as bromo or iodo on the benzenesulfonyl chloride were tolerated, as no cleavage of the C–Br or C–I bonds was observed under these conditions. The use of Pd/C presents several advantages compared to the previously employed homogeneous palladium catalysts, as it can be easily removed by filtration at the end of the reaction. The major side‐products of the reaction are HBr associated to Li2CO3. Therefore, this new protocol affords a very attractive synthetic scheme in terms of cost, simplicity and low environmental impact for the access to arylated heteroaromatics.

Carbonylation of Aryl Halides in the Presence of Heterogeneous Catalysts

Palladium-catalyzed carbonylation in the presence of organic and organometallic nucleophiles serves as a powerful tool for the conversion of aryl/alkenyl halides or halide equivalents to carbonyl compounds and carboxylic acid derivatives. To circumvent the difficulties in product separation and recovery and reuse of the catalysts, associated with homogeneous reactions, supported counterparts of the homogeneous palladium catalysts were developed. The review intends to summarize the huge development that has been witnessed in recent years in the field of heterogeneous carbonylation. A great plethora of supports, organic modifiers on solid surfaces stabilizing metal particles, transition metal precursors, as well as alternative sources for CO was investigated. In most cases, careful optimization of reaction conditions was carried out. Besides simple model reactions, the synthesis of carbonyl compounds and carboxylic acid derivatives from substrates with different functionalities was performed. In some cases, causes of palladium leaching were clarified with detailed investigations. The advantages of immobilized catalysts were shown by several examples. The possibility of catalystrecycling was proved besides proving that metal contamination of the products could often be kept below the detection limit. At the same time, detailed investigations should be carried out to gain a better insight into the real nature of these processes.

Pd/C as Heterogeneous Catalyst for the Direct Arylation of (Poly)fluorobenzenes.

The potential of the heterogeneous catalyst 10 % Pd/C in the direct arylation of (poly)fluorobenzene derivatives with aryl bromides has been investigated. In general, high yields of biaryl derivatives were obtained by using tri-, tetra-, and pentafluorobenzenes, whereas mono- and difluorobenzenes exhibited poor reactivity. The regioselectivities of the arylation reactions were similar to those observed with homogeneous palladium catalysts. Both electron-withdrawing and -donating substituents, such as nitrile, nitro, acetyl, ester, trifluoromethyl, tert-butyl, methoxy, or methyl, on the aryl bromide were tolerated. Unexpectedly, tetrafluoro-substituted [1,1'-biphenyl]-4-ols were obtained from pentafluorobenzene at 150 °C due to a formal regioselective hydroxylation, whereas at lower temperatures the expected pentafluorobiphenyls were obtained. However, no C-F bond cleavage was observed with the other polyfluorobenzene derivatives. These arylation reactions were carried out with only 1 mol % Pd/C as the catalyst and KOAc as an inexpensive base. Therefore, this protocol represents a very attractive access to (poly)fluoro-substituted biphenyls in terms of cost, simplicity, and sustainable chemistry because the Pd/C catalyst can be easily removed at the end of the reaction, there is no contamination with phosphine ligand residues, and the major side-product of the reaction is KOAc⋅HBr.

Continuous-Flow Suzuki-Miyaura and Mizoroki-Heck Reactions under Microwave Heating Conditions.

Microwave-assisted continuous-flow reactions have attracted significant interest from synthetic organic chemists, especially process chemists from practical points of view, due to a less complicated shift to large-scale synthesis based on simple and continuous access to products with low energy requirements. In this personal account, we focused on the Suzuki-Miyaura and Mizoroki-Heck reactions, both of which are significantly important cross-coupling reactions for the synthesis of various functional materials. Microwave power is effective for heating. Typical homogeneous palladium catalysts, such as PdCl2 (PPh3 )2 , Pd(PPh3 )4 , and Pd(OAc)2 , as well as heterogeneous palladium catalysts, such as Pd-film, Pd/Al2 O3 , Pd/SiO2 , and Pd supported on polymers, can be used for these reactions.

Single atoms catalyze Suzuki reactions

As effective as the palladium-catalyzed Suzuki reaction is for forming carbon-carbon bonds, researchers see room for improvement. Homogeneous palladium catalysts can be tough to separate from produ...

Towards a process for the telomerization of butadiene with N-methylglucamine

The telomerization of 1,3-dienes with functionalized nucleophiles presents an atom efficient and selective synthesis of potential non-ionic surfactants. Crucial for application of these synthetic pathways is the effective recycling of the homogeneous palladium catalyst. In this work, we present the telomerization of 1,3-butadiene with the renewable aminopolyol N-methylglucamine to a non-ionic surfactant in an aqueous solvent system. In order to achieve phase separation, the addition of freshly added 1,3-butadiene instead of an additional solvent offers an elegant way of catalyst recycling. With this method, recycling of the catalyst is feasible; a total turnover number of 1456 was reached.

Thiol Functionalized Cross-Linked Chitosan Polymer Supporting Palladium for Oxidative Heck Reaction and Reduction of p-Nitrophenol

A novel porous cross-linked chitosan polymer was prepared by Schiff reaction of chitosan (CS) with terephthalic aldehyde (TPA), followed by modification with trimethoxysilylpropanethiol. Such functional CS polymer (CS-TPA) could serve as both support and stabilizer for homogeneous palladium (Pd2+) catalyst. The obtained heterogeneous catalyst (Pd/CS-TPA-SH) exhibited high catalytic activity and selectivity for the oxidative Heck reaction of benzene and ethyl acrylate. The excellent performance is mostly attributed to the –SH groups stabilized Pd2+ species. Furthermore, Pd/CS-TPA-SH can also be used as the catalyst for the reduction of p-nitrophenol at room temperature, showing high efficiency and steady reusability. A novel thiol functionalized cross-linked chitosan polymer supporting palladium is synthesized and proved to be a highly efficient catalyst for oxidative Heck reaction and nitrophenol reduction.

Low temperature selective hydrodeoxygenation of model lignin monomers from a homogeneous palladium catalyst

The molecular, homogeneous catalysts [Pd(tpy)Cl]Cl and [Ni(tpy)](PF6)2, where tpy is 2,2′:6′,2′′- terpyridine, have been utilized to perform selective hydrodeoxygenation of benzyl alcohol, benzaldehyde, and benzophenone under very mild conditions. The [Pd(tpy)Cl]Cl catalyst exhibits excellent catalytic activity, with the complete selectivity towards hydrodeoxygenation, even at room temperature. Results indicate that the single-site nature of the molecular catalysts is what leads to the complete selectivity and the absence of aromatic ring hydrogenation products. A two-step mechanism consisting of H2 activation by the catalyst to form a metal hydride complex, followed by selective hydrodeoxygenation is proposed. These results illustrate the possible advantages for the use of homogeneous catalysts in the conversion of lignin biomass to fuel or chemical feedstocks.

Advances in carbon nanotubes as efficacious supports for palladium-catalysed carbon–carbon cross-coupling reactions

Since the 1970s, palladium-catalysed carbon–carbon (C–C) bond formation has made a critical impact in organic synthesis. In early studies, homogeneous palladium catalysts were extensively used for this reaction with limitations such as difficulty in separation and recycling ability. Lately, heterogeneous palladium-based catalysts have shown promise as surrogates for conventional homogeneous catalysts in C–C coupling reactions, since the product is easy to isolate, while the catalyst is reusable and hence sustainable. Recently, a better part of these heterogeneous palladium catalysts are supported on carbon nanotubes (Pd/CNTs), that have shown superior catalytic performance and better recyclability since the CNT support imparts stability to the palladium catalyst. This review discusses the wide variety of surface functionalization techniques for CNTs that improve their properties as catalyst supports, as well as the methods available for loading the catalyst nanoparticles onto the CNTs. It will survey the literature where Pd/CNTs catalysts have been utilized for C–C coupling reactions, with particular emphasis on Suzuki–Miyaura and Mizoroki–Heck coupling reactions. It will also highlight some of the important parameters that affect these reactions.

Fe3O4@SiO2 Nanoparticles Decorated with Schiff base Complex of Pd(II) as a Magnetically Phosphine-free Catalyst for Heck-Mizoroki Coupling Reactions

Background: The palladium-catalyzed couplings of alkenes with aryl halides is considered as one of the most important methods for carbon-carbon bond formation and have been utilized in the areas of natural products, high performance materials, bioactive compounds, new drugs and many industrially useful chemicals. Although the homogeneous palladium catalysts offer several advantages concerning higher selectivity and yields, better tuning of chemoselectivity and high efficiency but commercializing most of homogeneous has not been possible because of recycling problem of the catalyst from the mixture of reaction. Therefore, for resolving this problem, immobilization of homogeneous Pd complexes via grafting to solid supports such as activated carbon, zeolites, silica or modified silica, polymers, nanoparticles, and magnetic core shells have been subject of great challenges. Methods: Fe3O4 nanoparticles was coated by silica gel and then decorated by Schiff base Pd complex to provide Fe3O4@SiO2/Schiff base/Pd(II) nanoparticles. After optimization of reaction parameters, Heck- Mizoroki coupling reaction of aryl halides with olefins was studied. Results: The magnetic Schiff base complex of Pd, as a phosphine free nanocatalyst, catalyzed efficiently Heck-Mizoroki carbon-carbon coupling reaction between aryl halides and alkenes and provided the desired products in high yields. The magnetic Pd complex was easily removed from the reaction mixture and reused for eight runs. Conclusion: A new efficient, simple and cost effective protocol was introduced for carbon-carbon bond formation via Heck-Mizoroki coupling reaction of aryl halides with olefins in high to excellent yields in short reaction times. These valuable advantages were achieved because of employing Fe3O4@SiO2/Schiff base/Pd(II) complex as a dispersible, phosphine free ligand, highly active, magnetically recoverable and reusable several times. Keywords: Aryl halides, C- C coupling, heck reaction, magnetic nanoparticles, n-butyl acrylate palladium Styrene.