Heterogeneous Palladium Research Articles

A Pd(ii)/Mg–La mixed oxide catalyst for cyanation of aryl C–H bonds and tandem Suzuki–cyanation reactions

We report direct cyanation of aromatic C–H bonds and tandem Suzuki–cyanation reactions catalyzed by a heterogeneous palladium impregnated magnesium–lanthanum mixed oxide catalyst.

Utility of a heterogeneous palladium catalyst for the synthesis of a molecular semiconductor via Stille, Suzuki, and direct heteroarylation cross-coupling reactions

Demonstration of the utility of a commercially available heterogeneous palladium catalyst in the synthesis of a relevant high performance molecular semiconductor.

Activation of Aryl Chlorides in Water under Phase-Transfer Agent-Free and Ligand-Free Suzuki Coupling by Heterogeneous Palladium Supported on Hybrid Mesoporous Carbon

In this study, heterogeneous palladium catalysts supported on ordered mesoporous cobalt oxide–carbon nanocomposites were applied to the water-mediated Suzuki coupling reaction of chlorobenzene and phenylboronic acid and exhibited a high yield of biphenyl (49%) under mild reaction conditions free of phase-transfer agents and ligands. Product yields in the reaction of aryl chlorides containing electron-withdrawing groups attached to their benzene ring can reach approximately 90%. Thiol-functionalized mesoporous silica, which can trap soluble Pd species, was used to confirm the negligible leaching in solution and therefore heterogeneous reaction. This heterogeneous catalyst is stable, showing unobvious activity loss after 10 catalytic runs. Characterization by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray absorption fine structure analysis, and N2 sorption techniques revealed intercalated CoO nanoparticles inside a carbon matrix with uniform mesopore sizes (∼3 n...

The Design and Synthesis of Novel 2,3-Dihydrobenzo[f]isoquinolin-4(1H)-ones via Sequential Ugi-Heck Reactions by Using an Efficient Heterogeneous Palladium Nanocatalyst

A facile and efficient synthesis of N-alkyl-2-(1, 2 dihydro-1-methylene-4-oxobenzo[f] isoquinoline-3(4H)-yl)-2-phenylacetamides is performed by the consecutive, two-step procedure that consists of Ugi and Heck reactions. The Heck reaction was performed both by homogenous and a designed heterogeneous catalyst. The heterogeneous catalyst is a coordinated palladium to 1, 10-phenanthroline attached to chitosan@Fe3O4 magnetite nanoparticles, which was shown to be more efficient than the homogenous Pd(OAc)2/PPh3 catalyst with good to excellent yields.

Selective Aerobic Benzylic Alcohol Oxidation of Lignin Model Compounds: Route to Aryl Ketones

AbstractA mild and chemoselective oxidation of the α‐alcohol in β‐O‐4′‐ethanoaryl and β‐O‐4′‐glycerolaryl ethers has been developed. The benzylic alcohols were selectively dehydrogenated to the corresponding ketones in 60–93 % yield. A one‐pot selective route to aryl ethyl ketones was performed. The catalytic system comprises recyclable heterogeneous palladium, mild reaction conditions, green solvents, and oxygen in air as oxidant. Catalytic amounts of a coordinating polyol were found pivotal for an efficient aerobic oxidation.

Biopolymer-Metal Complex Wool-Pd: An Efficient and Reusable Heterogeneous Catalyst for the Heck Cross-Coupling Reactions and Aerobic Oxidation of Alcohols in Aqueous Media

Heterogeneous palladium catalysts, which are supported by biopolymer, have been applied in water-mediated Heck and the oxidation of alcohols cyclic reaction without assistance of any phosphine ligands. More importantly, owing to the interconversion between the Pd0 and PdII oxidation states during the Heck and oxidation reaction course, the catalyst exhibits good activity in Heck cross-coupling reaction of bromobenzene with styrene and oxidation reaction of alcohols to corresponding aldehydes or ketones without overoxidation using air as the source of molecular oxygen. This heterogeneous wool-Pd catalyst is stable, shows negligible metal leaching, and can be reused several times in reactions without significant loss of activity and selectivity.

Palladium complex immobilized on graphene oxide–magnetic nanoparticle composites for ester synthesis by aerobic oxidative esterification of alcohols

A well dispersed magnetically separable palladium complex immobilized to magnetite–graphene oxide nanocomposite has been synthesized via solvothermal route. The successfully decorated graphene oxide sheets with the homogeneously dispersed iron nanoparticles and palladium(II) complex were proved by transmission electron microscopy. X-ray diffraction pattern of the synthesized catalyst revealed that palladium(II) complex was successfully immobilized to the support. Further, X-ray photoelectron spectroscopy confirmed that palladium is present in +2 oxidation state. The synthesized heterogeneous material was found to be an efficient catalyst for the oxidative esterification of alcohols with methanol by using molecular oxygen as oxidant. The developed catalyst was found to be more reactive than its homogeneous analog, i.e. PdCl2(CH3CN)2. Similarly, no reaction occurred in the presence of Pd(0)/magnetite–graphene nanocomposite catalyst. These studies confirmed that the palladium(II) ions are the main catalyst and superior reactivity of heterogeneous palladium catalyst is attributed to the promotion role of graphene support in the adsorption of reactant alcohol and oxygen. After the reaction, the catalyst was easily separated by external magnetic effect and reused for several runs with consistent catalytic activity without any detectable leaching.

ChemInform Abstract: Direct C sp2—H and C sp3—H Arylation Enabled by Heterogeneous Palladium Catalysts

AbstractReview: [43 refs.

Heterogeneous palladium catalyst constructed with cross-linked hyperbranched poly(phenylacetylene) as polymer support: A reusable highly active ppm-level catalyst for multiple cross-coupling reactions

We demonstrate in this work a unique strategy for the synthesis of heterogeneous Pd catalysts with the use of a hyperbranched poly(phenylacetylene) containing pendant alkyne groups as the cross-linkable polymer substrate. It utilizes the dual functions of Pd-based catalysts in catalyzing both alkyne polymerization/oligomerization and coupling reactions. In the synthesis, a homogeneous Pd(II) catalyst catalyzes the cross-linking of the hyperbranched polymer and simultaneously encapsulates itself into the cross-linked polymer matrix, rendering the heterogeneous catalyst at high yield and high percentage of Pd encapsulation. Three homogeneous catalysts having different ligands (triphenylphosphine, a diphosphine ligand, and a diimine ligand) have been examined for the cross-linking encapsulation and the resulting heterogeneous catalysts have been evaluated for their catalytic performance in coupling reactions. Among the various heterogeneous catalysts obtained, a triphenylphosphine-ligated catalyst, HBPPA-Pd-2, appears to be the optimum one. It shows high activity in catalyzing the Suzuki–Miyaura reactions, the Mizoroki–Heck reactions, and the allylic arylation reactions under air with the Pd loading at as low as mol ppm or even mol ppb levels relative to the reactants. Meanwhile, it facilitates the Suzuki–Miyaura reactions of challenging less reactive aryl chlorides/heteroaryl bromides and the Mizoroki–Heck reactions of aryl bromides as reactants. In addition, it behaves truly as a heterogeneous catalyst with high reusability and low catalyst leaching during the reactions.

Reusable, Highly Active Heterogeneous Palladium Catalyst by Convenient Self‐Encapsulation Cross‐Linking Polymerization for Multiple CarbonCarbon Cross‐Coupling Reactions at ppm to ppb Palladium Loadings

AbstractDesigning reusable high‐performance heterogeneous palladium (Pd) catalysts via convenient, economic synthesis is of great importance to the industrial applications of various carbon‐carbon cross‐coupling reactions. We demonstrate herein a convenient one‐pot self‐encapsulation synthesis of a heterogeneous Pd catalyst [Pd@PDEB, PDEB=poly(1,3‐diethynylbenzene)] directly from commercially available, economic precursors. In the synthesis, the formation of the cross‐linked polymer networks and Pd encapsulation are accomplished simultaneously, turning a homogeneous Pd polymerization catalyst into the heterogeneous cross‐coupling catalyst. As a unique, practical heterogeneous catalyst, Pd@PDEB shows remarkably high activity, high reusability, and high versatility towards at least four types of cross‐coupling reactions (Suzuki–Miyaura, Stille, allylic arylation, and Mizoroki–Heck reactions) with even difficult reactants (aryl chlorides and heteroaryl halides) under aerobic conditions with Pd loadings down to ppm or even ppb levels. Evidences from hot filtration and 3‐phase tests demonstrate the heterogeneous nature of the catalyst with very low Pd leaching and negligible contributions of leached homogeneous Pd species towards the coupling reactions.magnified image

γ-Valerolactone as a Renewable Dipolar Aprotic Solvent Deriving from Biomass Degradation for the Hiyama Reaction

γ-Valerolactone (GVL) can be a valid biobased replacement for toxic dipolar aprotic solvents especially in widely used cross-coupling reactions. In this contribution, we have proved that GVL can be a useful medium for the Hiyama reaction, and we developed a practical and efficient protocol for the Hiyama coupling using a nonexpensive and commercially available heterogeneous palladium catalyst without the use of any ligand or additive. Desired cross-coupling products 3a–m have been obtained in good to excellent yields (74–94%).

Copper‐Free Sonogashira Coupling Reaction Catalyzed by PVC‐Supported Triazine Palladium(II) Complex Under Aerobic Conditions

AbstractA PVC‐supported triazine palladium(II) complex is a highly active catalyst for the copper‐free Sonogashira coupling of aryl halides with terminal alkynes at room temperature under aerobic conditions. This phosphine‐free heterogeneous palladium catalyst can be easily recovered from the products and reused many times.

Continuous-flow Heck-Matsuda reaction: homogeneous versus heterogeneous palladium catalysts.

This study describes extensive investigations of the Heck-Matsuda reaction carried out by continuous-flow chemistry between aryl diazonium salts generated in situ and methyl acrylate. Our optimized procedures enable sequential aniline diazotization/palladium-catalyzed Heck-Matsuda reaction using either Pd(OAc)2 or PdEnCat 30 as respectively a homogeneous or a heterogeneous source of palladium. This safe chemistry that does not require the handling of hazardous aryl diazonium salts involves inexpensive reagents and solvents, under ligand- and base-free conditions.

N-alkynyl derivatives of 5-fluorouracil: susceptibility to palladium-mediated dealkylation and toxigenicity in cancer cell culture.

Palladium-activated prodrug therapy is an experimental therapeutic approach that relies on the unique chemical properties and biocompatibility of heterogeneous palladium catalysis to enable the spatially-controlled in vivo conversion of a biochemically-stable prodrug into its active form. This strategy, which would allow inducing local activation of systemically administered drug precursors by mediation of an implantable activating device made of Pd0, has been proposed by our group as a way to reach therapeutic levels of the active drug in the affected tissue/organ while reducing its systemic toxicity. In the seminal study of such an approach, we reported that propargylation of the N1 position of 5-fluorouracil suppressed the drug's cytotoxic properties, showed high stability in cell culture and facilitated the bioorthogonal restoration of the drug's pharmacological activity in the presence of extracellular Pd0-functionalized resins. To provide additional insight on the properties of this system, we have investigated different N1-alkynyl derivatives of 5-fluorouracil and shown that the presence of substituents near the triple bond influence negatively on its sensitivity to palladium catalysis under biocompatible conditions. Comparative studies of the N1- vs. the N3-propargyl derivatives of 5-fluorouracil revealed that masking each or both positions equally led to inactive derivatives (>200-fold reduction of cytotoxicity relative to the unmodified drug), whereas the depropargylation process occurred faster at the N1 position than at the N3, thus resulting in greater toxigenic properties in cancer cell culture.

A recoverable Pd nanocatalyst for selective semi-hydrogenation of alkynes: hydrogenation of benzyl-propargylamines as a challenging model

We describe a recyclable heterogeneous palladium nanocatalyst for the selective hydrogenation of alkynes to alkenes. The catalyst was prepared through the decomposition of the organometallic precursor Pd2(dba)3 over a magnetic support, obtaining well-dispersed Pd nanoparticles that formed exclusively on the support surface, with average diameter of 3.5 ± 0.8 nm. The catalytic activity was investigated in the hydrogenation reactions of alkenes and alkynes, and the chemo- and stereoselectivity were evaluated in the hydrogenation of benzyl-propargylamines. The catalyst is highly selective in performing semi-hydrogenation reactions under mild conditions and short reaction times, with good overall yields. Furthermore, it can be easily recovered and recycled, with no leaching of palladium detected, and activities and selectivity retained over multiple reaction cycles.

Direct C sp2H and C sp3H Arylation Enabled by Heterogeneous Palladium Catalysts

AbstractThis review gives an overview of direct CH arylation catalyzed by heterogeneous Pd catalysts. The efficiency of the different forms of heterogeneous Pd catalysts is discussed with a critical view of the transformations attainable. If experimental evidence is provided, mechanistic considerations on the true nature of the catalysis, that is, heterogeneous versus homogeneous, are discussed as well.

A molecular Pd(ii) complex incorporated into a MOF as a highly active single-site heterogeneous catalyst for C–Cl bond activation

The organic palladium complex Pd(H2bpydc)Cl2 (H2bpydc = 2,2′-bipyridine-5,5′-dicarboxylic acid) was immobilized on a porous metal–organic framework UiO-67 (Zr6O4(OH)4(bpdc)6, bpdc = para-biphenyldicarboxylate) using a direct incorporation strategy. The use of a large amount of the H2bpdc ligand (90 mol% of the mixed ligands) that can't chelate the Pd complex allowed the formation of isolated Pd single active sites uniformly distributed in the MOF network. Pd(II) doped UiO-67 is isostructural to the parent UiO-67 framework, with a high surface area and pore volume of ca. 2000 m2 g−1 and 0.79 cm3 g−1, respectively. The material was highly efficient in the catalytic conversion of aryl chlorides, showing remarkably higher activity than the homogeneous Pd counterparts. High yields were achieved in Heck and Suzuki–Miyaura coupling reactions of chloroarenes bearing a wide range of substituents. Moreover, the catalyst was recoverable and reusable, giving essentially identical activity after at least 5 cycles. The combination of the advantages of both homogeneous molecular Pd catalysts and solid MOF structures in this system may bring new opportunity in the development of highly active heterogeneous palladium catalysts for a variety of Pd-catalyzed transformations.

Development and bioorthogonal activation of palladium-labile prodrugs of gemcitabine.

Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd0-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd0-cleavable groups in positions that are mechanistically relevant for gemcitabine’s pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs’ cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

ChemInform Abstract: Amine Formylation via Carbon Dioxide Recycling Catalyzed by a Simple and Efficient Heterogeneous Palladium Catalyst.

A simple and efficient Pd/Al2O3-NR-RD catalyst was prepared by depositing palladium on a shape controllable Al2O3-NR support through a two-step process that involves hydrothermal synthesis of Al2O3-NRs followed by reductive-deposition of palladium. This catalyst showed high activity in the catalytic formylation of amines by CO2–H2 under mild conditions with up to 96% yield.

Total Synthesis of Capsaicin Analogues from Lignin‐Derived Compounds by Combined Heterogeneous Metal, Organocatalytic and Enzymatic Cascades in One Pot

AbstractThe total synthesis of capsaicin analogues was performed in one pot, starting from compounds that can be derived from lignin. Heterogeneous palladium nanoparticles were used to oxidise alcohols to aldehydes, which were further converted to amines by an enzyme cascade system, including an amine transaminase. It was shown that the palladium catalyst and the enzyme cascade system could be successfully combined in the same pot for conversion of alcohols to amines without any purification of intermediates. The intermediate vanillylamine, prepared with the enzyme cascade system, could be further converted to capsaicin analogues without any purification using either fatty acids and a lipase, or Schotten–Baumann conditions, in the same pot. An aldol compound (a simple lignin model) could also be used as starting material for the synthesis of capsaicin analogues. Using L‐alanine as organocatalyst, vanillin could be obtained by a retro‐aldol reaction. This could be combined with the enzyme cascade system to convert the aldol compound to vanillylamine in a one‐step one‐pot reaction.magnified image