Palladium Source Research Articles

Palladium-Catalyzed Domino Cycloisomerization/Double Condensation of Acetylenic Acids with Dinucleophiles

Metal-catalyzed cascade processes based on hydrofunctionalization of alkynes are receiving much more attention because of their potential to provide advantageous approaches to otherwise synthetically challenging compounds. An alternative catalyst system has been found for the domino cycloisomerization/cyclocondensation reaction involving acetylenic acids and heterodinucleophiles. A CNN pincer palladium(II) complex, acting as a homogeneous catalyst, provides the corresponding polyheterocycles with a higher substrate/catalyst ratio. Other palladium sources were also tested and discarded, and a number of mechanistic studies including poisoning assays, kinetic plots, TEM images, XRD spectra and UPLC-MS analysis of reaction intermediates were conducted in order to shed light on the role of this pincer catalyst and the catalytic cycle involved in the cascade reaction. As a result, a more nuanced mechanism is tentatively proposed.

A 5-FU Precursor Designed to Evade Anabolic and Catabolic Drug Pathways and Activated by Pd Chemistry In Vitro and In Vivo.

5-Fluorouracil (5-FU) is an antineoplastic antimetabolite that is widely administered to cancer patients by bolus injection, especially to those suffering from colorectal and pancreatic cancer. Because of its suboptimal route of administration and dose-limiting toxicities, diverse 5-FU prodrugs have been developed to confer oral bioavailability and increase the safety profile of 5-FU chemotherapy regimens. Our contribution to this goal is presented herein with the development of a novel palladium-activated prodrug designed to evade the metabolic machinery responsible for 5-FU anabolic activation and catabolic processing. The new prodrug is completely innocuous to cells and highly resistant to metabolization by primary hepatocytes and liver S9 fractions (the main metabolic route for 5-FU degradation), whereas it is rapidly converted into 5-FU in the presence of a palladium (Pd) source. In vivo pharmokinetic analysis shows the prodrug is rapidly and completely absorbed after oral administration and exhibits a longer half-life than 5-FU. In vivo efficacy studies in a xenograft colon cancer model served to prove, for the first time, that orally administered prodrugs can be locally converted to active drugs by intratumorally inserted Pd implants.

Synthesizing Highly Fluorinated Oligophenyls via Negishi Coupling of Fluoroarylzinc Pivalates

AbstractPreviously established general synthetic methods for the synthesis of highly fluorinated biphenyls using Suzuki–Miyaura protocols require the use of organoboron compounds, which are not very stable under reactions conditions and thus need to be used in large excess. Herein, we report an improved general strategy for the synthesis of highly fluorinated biphenyls, terphenyls, and phenyl-substituted terphenyls using organozinc pivalates. The influence of several parameters was investigated: (1) in a series of monodentate phosphine ligands, X-Phos showed the best performance; (2) a higher yield was obtained for substrates bearing less steric hindrance or lower amount of fluorine substitution; (3) as iodinated substrates decomposed during the reaction, brominated electrophiles were found to be superior. The presented protocol is scalable, versatile, and works with commonly used and commercially available phosphine ligands (X-Phos) and palladium sources (Pd2dba3). Also, it does not require excess nucleophile for terphenyl synthesis and only a slight excess is needed for the preparation of phenyl substituted terphenyls.

Palladium-catalyzed aryl group transfer from triarylphosphines to arylboronic acids

A study of Pd-catalyzed arylation of arylboronic acids with triarylphosphines is presented. Various parameters of this transformation, such as the oxygen presence, choice of solvent, temperature, palladium source, bases and oxidants, were tested and the optimal conditions of the aryl transfer were determined. The effect of electron-withdrawing and electron-donating substituents on the aryl groups of both reactants was also investigated. The unusual transfer of the acetate group from Pd(OAc)2 to p-nitrophenylboronic acid in the presence of PAr3 is reported. A plausible mechanism of the Pd-catalyzed aryl group transfer from PAr3 to the arylboronic acid is proposed.

Direct Arylation in the Presence of Palladium Pincer Complexes.

Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed.

Pd-loaded “Two-in-one” Covalent Organic Framework Composite Material: Synthesis, Characterization and Detection of Bisphenol A

We report a novel type of Pd-BFBAPy-COF (Pd-COF) loaded with Pd-NPs was synthesized for the first time by using “two-in-one” imine covalent organic framework materials as carrier. By using BFBAPy-COF (Py-COF) as the carrier and H2PdCl4 as the palladium source, Py-COF and Pd-NPs were combined by a simple heating and reflux method to successfully prepare Pd-COF. Through X-ray photoelectron spectroscopy (XPS) and other methods, it is proved that the loading of Pd-NPs on Pd-COF is completed by coordination. Finally, the application of Pd-COF as electrode coating material in the detection of Bisphenol A (BPA) by differential pulse voltammetry (DPV) shows that Pd-COF has a good electrochemical induction to BPA. This work provides a cheap and facile synthesis route for the preparation of an electrochemical detection material with practical value.

Defining the Qualities of High-Quality Palladium on Carbon Catalysts for Hydrogenolysis.

Palladium-catalyzed hydrogenolysis is often the final step in challenging natural product total syntheses and a key step in industrial processes producing fine chemicals. Here, we demonstrate that there is wide variability in the efficiency of commercial sources of palladium on carbon (Pd/C) resulting in significant differences in selectivity, reaction times, and yields. We identified the physicochemical properties of efficient catalysts for hydrogenolysis: (1) small Pd/PdO particle size (2) homogeneous distribution of Pd/PdO on the carbon support, and (3) palladium oxidation state are good predictors of catalytic efficiency. Now chemists can identify and predict a catalyst’s efficiency prior to the use of valuable synthetic material and time.

Synthesis and structural characterizations of Pd(II) complexes bearing the new hexahydropyrimidine and tetrahydropyrimidinium based bis(pyrazole) ligands with DFT studies

The one pot reaction between 1,3­-diaminopropane, 3,5-dimethylpyrazole and paraformaldehyde afforded 1,3­-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)hexahydropyrimidine 1 in an excellent yield. The reaction of 1 with one equivalent of N-bromosuccinimide in DME gave the oxidized product 2; the same reaction in the presence of 4 equivalents of NBS yielded the pyrazole ring brominated product. Treatment of 2 with NH4PF6 gave its PF6− salt 3. Conversely, its BF4− salt was obtained directly from the reaction of AgBF4 with 1. Treatment of 3 with palladium(II) precursors gave two monomeric trans chelated complexes containing acetate and chloride ions as their PF6− salts. Conversely, 1 reacts with palladium(II) source to give the dimeric 20-membered palladacycle. The monomeric complexes are rigid molecules, whereas the dimer complex is fluxional as shown by their 1H NMR spectra. From the low temperature NMR study of the dimer complex the broad signals in the room temperature NMR spectrum are attributed to the fast interconversion between its conformers. All compounds were characterized by both spectroscopic and X-ray methods, and in some cases by CHN analysis. DFT calculations were performed to understand the formation of the chelate complex against its anticipated NHC complex containing the 6-membered ring and the binuclear complex against a monomeric complex in terms of 5- and 6-membered ring strain energies.

The Real Structure of Pd(OAc)2 in Various Solvents†

Main observation and conclusionPd(OAc)2 is an extensively utilized palladium source in the palladium initiated transformations either directly or as a catalyst precursor. However, the comprehension of the real structure of Pd(OAc)2 in solution is still vague. In this work, the structure of palladium acetate in solution was studied in detail by using X‐ray absorption fine structure (XAFS) spectroscopy. The results demonstrate that monomer is the main form for Pd(OAc)2 in the solution of 1,4‐dioxane, N,N‐dimethylacetamide (DMA), N,N‐dimethylformamide (DMF), 1,2‐dimethoxyethane (DME), MeCN and dimethyl sulfoxide (DMSO). In addition, Pd(II) could be reduced to Pd(0) in ethanol solution. The structural information in this research will benefit the understanding of the mechanism of Pd(OAc)2 involved organic reactions.

Sequential Sonogashira/intramolecular aminopalladation/cross-coupling of ortho-ethynyl-anilines catalyzed by a single palladium source: rapid access to 2,3-diarylindoles.

We have developed a practical and efficient one-pot protocol for the synthesis of 2,3-diarylindoles via Pd-catalyzed bis-arylative cyclization of various o-ethynylanilines with aryl iodides. Mechanism studies showed that a Pd-catalyzed Sonogashira reaction took place firstly, giving an internal alkyne intermediate, which subsequently underwent intramolecular aminopalladation/cross-coupling to give access to 2,3-diarylindoles. The present methodology exhibits a broad substrate scope, producing various 2,3-diaryl indoles bearing two different aryl groups.

Implementation of Sustainable Solvents in Green Polymerization Approaches

AbstractIn modern polymer chemistry directed toward the synthesis of conjugated materials, the synthetic routes devised to achieve the process sustainability are based on CH bond activation. This prerequisite distinguishes both the tandem Suzuki−Heck as well as the direct arylation polymerizations (DArP); however, their compatibility with environmentally benign solvents still represents a challenge. In this paper, the implementation of sustainable solvents for the synthesis of poly(9,9‐dioctylfluorenylene‐vinylene) by using the traditional Pd(AcO)2/P(o‐Tol)3/NEt3 catalytic system is described. It is assessed that selected green solvents (i.e., anisole and propylene carbonate) constitute the ideal media for the tandem Suzuki–Heck polymerization. Furthermore, by modulating medium polarity using mixtures of these green solvents and changing the reaction temperature, a suitable compromise between high molecular weights and regioregularity of the resulting polymers is reached. Conversely, the presence of propylene carbonate is deleterious for the DArP of 2‐bromo‐3‐hexylthiophene, while it is found that catalyst performances in anisole strictly depend on the palladium source used. The best conditions are obtained using PdCl2(PPh3)2 as the precatalyst, affording a highly regioregular (93%) poly(3‐hexylthiophene) in quantitative yields and high molecular weights (26.7 kg mol−1).

Palladium-Protein Oxidative Addition Complexes by Amine-Selective Acylation.

Palladium oxidative addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, a new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies on an amine-selective acylation reaction that occurs without modification of a preformed palladium(II)-aryl group. Once transferred onto a protein substrate, the palladium(II)-aryl group facilitates conjugation by undergoing reaction with a second, cysteine-containing protein. This operationally simple method is applicable to native, nonengineered enzymes as well as antibodies and is carried out in an aqueous setting and open to air. The resulting Pd-protein OACs are stable, storable reagents that retain biological activity and can be used to achieve protein-protein cross-coupling at nanomolar concentrations within hours.

Unexpected electocatalytic activity of a micron-sized carbon sphere-graphene (MS-GR) supported palladium composite catalyst for ethanol oxidation reaction (EOR)

For the first time, a hybrid carbon material consisting of micron-sized carbon spheres and graphene (denoted as MS-GR) was prepared via a hydrothermal method. In this work, micron-sized carbon spheres were prepared using glucose and 1-butyl-3-methylimidazolium tetrafluoroborate as the starting materials through a hydrothermal method, and graphene was employed as purchased. One-pot and two-step hydrothermal methods were respectively employed to prepare MS-GR, and in each preparation method, three different amounts of graphene were added in the preparation system while maintaining the added amounts of other reagents identical for each prepared catalyst. As a result, six kinds of hybrid carbon materials were fabricated in this work. Next, MS-GR supported palladium composite catalysts were fabricated through a hydrothermal method using PdO·H2O as the palladium source. Metallic Pd particles, metallic Pd particles along with PdO were indicated by XRD patterns to be the main substances of the one-pot and two-step hydrothermally prepared MS-GR supported catalysts, respectively. As presented by the SEM images, micron-sized carbon spheres and individual graphene sheets as well as the small particles were exhibited clearly in all prepared catalysts, suggesting that all the resultant catalysts were a composite material. Most importantly, as indicated by the CV and CA curves, all synthesized catalysts showed obvious electrocatalytic activities for EOR. In particular, the peak current density of peak f for EOR in the CV curves on catalyst t-4 was as high as 29.1 mA cm-2, significantly larger than the previously reported values. And the current density of EOR measured by CA test on catalyst t-4 was retained as high as 2.83 mA cm-2 after 600 s, showing an excellent electrocatalytic durability. In this work, a carbon material constructed by micron-sized carbon spheres and graphene as well as a novel MS-GR supported Pd catalyst was developed for the first time, which was very helpful to the final commercialization of a Pd-based EOR electrocatalyst due to the greatly reduced the preparation cost and the facile preparation procedure.

Differences in the Performance of Allyl Based Palladium Precatalysts for Suzuki-Miyaura Reactions.

Palladium(II) precatalysts are used extensively to facilitate cross-coupling reactions because they are bench stable and give high activity. As a result, precatalysts such as Buchwald's palladacycles, Organ's PEPPSI species, Nolan's allyl-based complexes, and Yale's 1-tert-butylindenyl containing complexes, are all commercially available. Comparing the performance of the different classes of precatalysts is challenging because they are typically used under different conditions, in part because they are reduced to the active species via different pathways. However, within a particular class of precatalyst, it is easier to compare performance because they activate via similar pathways and are used under the same conditions. Here, we evaluate the activity of different allyl-based precatalysts, such as (η3-allyl)PdCl(L), (η3-crotyl)PdCl(L), (η3-cinnamyl)PdCl(L), and (η3-1-tert-butylindenyl)PdCl(L) in Suzuki-Miyaura reactions. Specifically, we evaluate precatalyst performance as the ancillary ligand (NHC or phosphine), reaction conditions, and substrates are varied. In some cases, we connect relative activity to both the mechanism of activation and the prevalence of the formation of inactive palladium(I) dimers. Additionally, we compare the performance of in situ generated precatalysts with commonly used palladium sources such as tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3), bis(acetonitrile)dichloropalladium(II) (Pd(CH3CN)2Cl2), and palladium acetate. Our results provide information about which precatalyst to use under different conditions.

Modified palladium/chitosan/graphene nanocomposites for the reduction of nitrophenolic compounds

Chitosan (Chit) cross-linked via glutaraldehyde to graphene oxide (GO) was prepared as the basic nanocomposite support for further modification. The Chit/GO nanocomposite was modified with carbon nanotubes (CNT) and/or magnetite (Fe3O4), to separate the GO sheets even further and/or to render the nanocomposite magnetic. Palladium nanoparticles (Pd NPs) was embedded into the matrix of the nanocomposite using Pd(OAc)2 as the palladium source. SEM and TEM were used to visually investigated the sheet separation of GO, the entrapment of GO in chitosan and embedding of Pd NPs in the nanocomposite matrix. The properties of the GO nanocomposites were investigated by Attenuated Total Reflection Fourier transform infra-red spectroscopy (ATR FTIR), Thermo-Gravimetric Analysis (TGA), Inductively Coupled Plasma–Optical emission spectrometry (ICP-OES) and X-ray Photoelectron Spectroscopy (XPS). The applicability of these palladium-containing nanocomposites was investigated for the reduction of nitrophenol in the presence of NaBH4. The reduction reactions were followed by UV-Vis and their kinetic parameter were determined. All five Pd-containing nanocomposites displayed excellent catalytic activity towards the reduction of aromatic nitroarenes. The reduction of the nitrophenol compounds over all the nanocomposites showed pseudo first order kinetics with the estimate k′obs, between 2.0 × 10−3 and 2.5 × 10−2 s−1, and a possible mechanism for the reaction is proposed.

Effect of phosphonium ionic liquid/Pd ratio on the catalytic activity of palladium nanoparticles in Suzuki cross-coupling reaction

Phosphonium salts were synthesized and used as support for palladium nanoparticles. It was demonstrated that the catalytic behavior of palladium nanoparticles in Suzuki cross-coupling reaction is determined by the ratio of the phosphonium ionic liquid to palladium source and the nature of the stabilizer. Transition electron microscopy and dynamic light scattering techniques allowed to determine the most effective range of stabilizer concentration in the reaction media.

Intracellular Reactions Promoted by Bis(histidine) Miniproteins Stapled Using Palladium(II) Complexes

AbstractThe generation of catalytically active metalloproteins inside living mammalian cells is a major research challenge at the interface between catalysis and cell biology. Herein we demonstrate that basic domains of bZIP transcription factors, mutated to include two histidine residues at i and i+4 positions, react with palladium(II) sources to generate catalytically active, stapled pallado‐miniproteins. The resulting constrained peptides are efficiently internalized into living mammalian cells, where they perform palladium‐promoted depropargylation reactions without cellular fixation. Control experiments confirm the requirement of the peptide scaffolding and the palladium staple for attaining the intracellular reactivity.

Optimization of the Reaction Conditions for Direct Arylation Polymerizations in a Sustainable Solvent

AbstractDirect arylation polymerization (DArP) relieves the synthesis of conjugated polymers from the use of hazardous and toxic reagents typical of the traditional protocols. However, the compatibility with environmentally benign, nonhazardous, and low‐cost solvents still represents the critical aspect for projecting DArP as an industrial‐scale method for the preparation of conjugated polymers. In this study, a “green” solvent (i.e., cyclopentyl methyl ether) is implemented for the obtainment of poly(3‐hexylthiophene) by DArP reaction, in order to explore sustainable reaction conditions also regarding the catalytic system and the base quantity, which equally undermine the sustainability of the DArP protocol. Considering the molecular weights as the indicator of precatalyst performance in determined conditions, it is established that the cheapest palladium source (i.e., PdCl2) combined with two equivalents of (o‐anisyl)3P is able to yield the best results in the green ethereal solvent. Furthermore, it is found how, with respect to the common DArP protocols, the quantity of the expensive base (i.e., Cs2CO3) can be reduced in these reaction conditions without compromising molecular weights and regioregularity of the resulting polymer. These optimized reaction conditions can be extended to the copolymerization of other monomer units with satisfactory results in terms of molecular weights.

Intracellular Reactions Promoted by Bis(histidine) Miniproteins Stapled Using Palladium(II) Complexes.

The generation of catalytically active metalloproteins inside living mammalian cells is a major research challenge at the interface between catalysis and cell biology. Herein we demonstrate that basic domains of bZIP transcription factors, mutated to include two histidine residues at i and i+4 positions, react with palladium(II) sources to generate catalytically active, stapled pallado-miniproteins. The resulting constrained peptides are efficiently internalized into living mammalian cells, where they perform palladium-promoted depropargylation reactions without cellular fixation. Control experiments confirm the requirement of the peptide scaffolding and the palladium staple for attaining the intracellular reactivity.

Imide-Fused Diazatetracenes: Synthesis, Characterization, and Application in Perovskite Solar Cells.

A series of imide-fused diazatetracenes were synthesized via Buchwald-Hartwig C-N coupling with a highly active palladium source. The introduction of an imide segment effectively lowers the LUMO levels compared with that of unsubstituted diazatetracene. By adjusting the alkyl chains of the diazatetracenes, different solid-state packings were achieved, resulting in distinct photoluminescent behaviors. Their electron-transporting properties were demonstrated in the proof-of-concept Perovskite solar cells as electron transporting layers.