Carboxymethylcellulose‐supported palladium nanoparticles generated in situ from palladium(II) carboxymethylcellulose as an efficient and reusable catalyst for ligand‐ and base‐free Heck–Matsuda and Suzuki–Miyaura couplings

A novel palladium(II) carboxymethylcellulose (CMC‐Pd^II) was prepared by direct metathesis from sodium carboxymethylcellulose and PdCl₂ in aqueous solution. Its catalytic activities were explored for Heck–Matsuda reactions of aryldiazonium tetrafluoroborate with olefins, and Suzuki–Miyaura couplings of aryldiazonium tetrafluoroborate with arylboronic acid. Both reactions proceeded at room temperature in water or aqueous ethanol media without the presence of any ligand or base, to provide the corresponding cross‐coupling products in good to excellent yields under atmospheric conditions. The CMC‐Pd^II and carboxymethylcellulose‐supported palladium nanoparticles (CMC‐Pd⁰) formed in situ in the reactions were characterized using Fourier transform infrared spectroscopy, X‐ray diffraction, inductively coupled plasma atomic emission spectrometry, and scanning and transmission electron microscopies. The homogeneous nature of the CMC‐Pd⁰ catalyst was confirmed via Hg(0) and CS₂ poisoning tests. Moreover, the CMC‐Pd⁰ catalyst could be conveniently recovered by simple filtration and reused for at least ten cycles in Suzuki–Miyaura reactions without apparently losing its catalytic activity. The catalytic system not only overcomes the basic drawbacks of homogeneous catalyst recovery and reuse but also avoids the need to fabricate palladium nanoparticles in advance. Copyright © 2015 John Wiley & Sons, Ltd.     

Exploring the Oxidative‐Addition Pathways of Phenyl Chloride in the Presence of PdII Abnormal N‐Heterocyclic Carbene Complexes: A DFT Study

DFT calculations were performed to elucidate the oxidative addition mechanism of the dimeric palladium(II) abnormal N‐heterocyclic carbene complex 2 in the presence of phenyl chloride and NaOMe base under the framework of a Suzuki–Miyaura cross‐coupling reaction. Pre‐catalyst 2 undergoes facile, NaOMe‐assisted dissociation, which led to monomeric palladium(II) species 5 , 6 , and 7 , each of them independently capable of initiating oxidative addition reactions with PhCl. Thereafter, three different mechanistic routes, path a, path b, and path c, which originate from the catalytic species 5 , 7 , and 6 , were calculated at M06‐L ‐D3(SMD)/LANL2TZ(f)(Pd)/6–311++G**//M06‐L/LANL2DZ(Pd)/6–31+G* level of theory. All studied routes suggested the rather uncommon Pd^II/Pd^IV oxidative addition mechanism to be favourable under the ambient reaction conditions. Although the Pd⁰/Pd^II routes are generally facile, the final reductive elimination step from the catalytic complexes were energetically formidable. The Pd^II/Pd^IV activation barriers were calculated to be 11.3, 9.0, 26.7 kcal mol^?1 (ΔΔ^≠G_L^S‐D3) more favourable than the Pd^II/Pd⁰ reductive elimination routes for path a, path b, and path c, respectively. Out of all the studied pathways, path a was the most feasible as it comprised of a Pd^II/Pd^IV activation barrier of 24.5 kcal mol^?1 (ΔG_L^S‐D3). To further elucidate the origin of transition‐state barriers, EDA calculations were performed for some key saddle points populating the energy profiles.     

Immobilization of palladium(II)‐containing bis(imidazolium) ligand on ion‐exchange resins: efficient and reusable catalysts for CC coupling reactions

Suzuki reactions catalysed by a palladium(II) complex of a functionalized bis(imidazolium) ligand, Pd^II(BIM), immobilized on Dowex 50 WX8 and Amberlite IR‐120 ion‐exchange resins as heterogeneous, recyclable and active catalysts are reported. The catalysts, Pd^II(BIM)@Amberlite IR‐120 and Pd^II(BIM)@Dowex 50 WX8, were characterized using Fourier transform infrared and diffuse‐reflectance UV–visible spectroscopies and scanning electron microscopy. These heterogeneous catalysts are oxygen‐insensitive and air‐ and moisture‐stable in C? C coupling reactions, and are reusable several times without significant loss of their catalytic activity. Copyright © 2015 John Wiley & Sons, Ltd.     

High‐Oxidation‐State Palladium Catalysis: New Reactivity for Organic Synthesis

Recent years have seen the rapid development of a new field of palladium catalysis in organic synthesis. This chemistry takes place outside the usually encountered Pd⁰/Pd^II cycles. It is characterized by the presence of strong oxidants, which prevent further palladium(II)‐promoted reactions at a given point of the catalytic cycle by selective metal oxidation. The resulting higher‐oxidation‐state palladium complexes have been used to develop a series of new synthetic transformations that cannnot be realized within conventional palladium catalysis. This type of catalysis by palladium in a higher oxidation state is of significant synthetic potential.     

Palladium‐Catalyzed Desymmetrization of Silacyclobutanes with Alkynes to Silicon‐Stereogenic Silanes: A Density Functional Theory Study

The palladium‐catalyzed desymmetrization of silacyclobutanes using electron‐deficient alkynes proceeds with high enantioselectivity in the presence of a chiral P ligand; this provides a facile approach for the synthesis of novel silicon‐stereogenic silanes. In this work, we used hybrid density functional theory (DFT) to elucidate the mechanism of the palladium‐catalyzed desymmetrization of silacyclobutanes with dimethyl acetylenedicarboxylate. Full catalytic cycle including two different initiation modes that were proposed to be a possible initial step to the formation of the 1‐pallada‐2‐silacyclopentane/alkyne intermediate—the oxidative addition of the palladium complex to the silacyclobutane Si?C bond (cycle MA) or coordination of the Pd⁰ complex with the alkyne C≡C bond (cycle MB)—have been studied. It was found that the ring‐expansion reaction began with cycle MB is energetically more favorable. The formation of a seven‐membered metallocyclic Pd^II intermediate was found to be the rate‐determining step, whereas the enantioselectivity‐determining step, oxidative addition of silacyclobutane to the three‐membered metallocyclic Pd^II intermediate, was found to be quite sensitive to the steric repulsion between the chiral ligand and silacyclobutane.     

Palladium‐Catalyzed Direct Thiolation of Aryl CH Bonds with Disulfides

A catalytic variant of the direct thiolation of arenes, bearing directing groups, with disulfides or thiols has been developed under palladium and copper co‐catalysis. Both sulfenyl moieties of the disulfide could be incorporated into the thiolated products, therefore, the reactions reached completion with only half an equivalent of disulfide, with respect to the starting arene. Experimental evidence suggested that the reaction proceeds through a Pd^II/Pd^IV mechanism.     

Synthesis of Imides by Palladium‐Catalyzed C?H Functionalization of Aldehydes with Secondary Amides

An efficient palladium‐catalyzed C? H functionalization of aldehydes with various N‐substituted N‐heteroarene‐2‐carboxamides has been developed for the synthesis of secondary imides. The reaction tolerates various functionalities, such as methoxy, fluoro, chloro, and bromo groups. A tentative radical mechanism for a Pd^II/Pd^IV catalytic cycle is proposed.     

Exclusive Detection of Sub‐Nanomolar Levels of Palladium(II) in Water: An Excellent Probe for Multiple Applications

A new colorimetric probe has been developed for the detection and estimation of Pd^II at sub‐nanomolar concentrations. The probe consisted of rhodamine (signaling unit), which was linked with a bis‐picolyl moiety (binding site) through a phenyl ring. Pd^II induced opening of the spirolactam ring of the probe with the generation of a prominent pink color. The excellent selectivity of the probe towards Pd^II over Pd⁰ or Rh^II ensured its potential utility for the detection of residual palladium contamination in pharmaceutical drugs and in Pd‐catalyzed reactions. The probe showed a “turn‐on” (bright yellow) fluorescence upon the addition of Pd^II, which made it suitable for the detection of Pd contaminants in mammalian cells.     

Trinuclear Pd3O2 Intermediate in Aerobic Oxidation Catalysis

The activation of O₂ is a key step in selective catalytic aerobic oxidation reactions mediated by transition metals. The bridging trinuclear palladium species, [(LPd^II)₃(μ³‐O)₂]²⁺ (L=2,9‐dimethylphenanthroline), was identified during the [LPd(OAc)]₂(OTf)₂‐catalyzed aerobic oxidation of 1,2‐propanediol. Independent synthesis, structural characterization, and catalytic studies of the trinuclear compound show that it is a product of oxygen activation by reduced palladium species and is a competent intermediate in the catalytic aerobic oxidation of alcohols. The formation and catalytic activity of the trinuclear Pd₃O₂ species illuminates a multinuclear pathway for aerobic oxidation reactions catalyzed by Pd complexes.     

Palladium(II)‐Initiated Catellani‐Type Reactions

The Catellani reaction is known as a powerful strategy for the expeditious synthesis of highly substituted arenes and benzo‐fused rings, which are usually difficult to access through traditional cross‐coupling strategies. It utilizes the synergistic interplay of palladium and norbornene catalysis to facilitate sequential ortho C?H functionalization and ipso termination of aryl halides in a single operation. In classical Catellani‐type reactions, aryl halides are mainly used as the substrates, and a Pd⁰ catalyst is required to initiate the reaction. Nevertheless, recent advances showcase that Catellani‐type reactions can also be initiated by a Pd^II catalyst with different starting materials instead of aryl halides via different reaction mechanisms and under different conditions. This emerging concept of Pd^II/norbornene cooperative catalysis has significantly advanced Catellani‐type reactions, thus enabling future developments of this field. In this Minireview, Pd^II‐initiated Catellani‐type reactions and their application in the synthesis of bioactive molecules are summarized.     

Formation of XPhos-Ligated Palladium(0) Complexes and Reactivity in Oxidative Additions

Understanding the nature of the intermediate species operating within a palladium catalytic cycle is crucial for developing efficient cross-coupling reactions. Even though the XPhos/Pd(OAc)₂ catalytic system has found numerous applications, the nature of the active catalytic species remains elusive. A Pd⁰ complex ligated to XPhos has been detected and characterized in situ for the first time using cyclic voltammetry and NMR techniques. In the presence of XPhos, Pd(OAc)₂ initially associates with the ligand to form a complex in solution, which has been characterized as Pd^II(OAc)₂(XPhos). This Pd^II center is then reduced to the Pd⁰(XPhos)₂ species by an intramolecular process. This study also sheds light on the formation of Pd^I–Pd^I dimers. Finally, a kinetic study probes a dissociative mechanism for the oxidative addition with aryl halides involving Pd⁰(XPhos) as the reactive species in equilibrium with the unreactive Pd⁰(XPhos)₂. Remarkably, the reportedly poorly reactive PhCl reacts at room temperature in the oxidative addition, which confirms the crucial role of the XPhos ligand in the activation of aryl chlorides.     

Catalytic Behavior of Mono‐N‐Protected Amino‐Acid Ligands in Ligand‐Accelerated C−H Activation by Palladium(II)

Mono‐N‐protected amino acids (MPAAs) are increasingly common ligands in Pd‐catalyzed C?H functionalization reactions. Previous studies have shown how these ligands accelerate catalytic turnover by facilitating the C?H activation step. Here, it is shown that MPAA ligands exhibit a second property commonly associated with ligand‐accelerated catalysis: the ability to support catalytic turnover at substoichiometric ligand‐to‐metal ratios. This catalytic role of the MPAA ligand is characterized in stoichiometric C?H activation and catalytic C?H functionalization reactions. Palladacycle formation with substrates bearing carboxylate and pyridine directing groups exhibit a 50–100‐fold increase in rate when only 0.05 equivalents of MPAA are present relative to Pd^II. These and other mechanistic data indicate that facile exchange between MPAAs and anionic ligands coordinated to Pd^II enables a single MPAA to support C?H activation at multiple Pd^II centers.     

Carbonylation of nitrobenzene in methanol with palladium bidentate phosphane complexes: an unexpectedly complex network of catalytic reactions, centred around a Pd-imido intermediate

The reactivity of palladium complexes of bidentate diaryl phosphane ligands (P₂) was studied in the reaction of nitrobenzene with CO in methanol. Careful analysis of the reaction mixtures revealed that, besides the frequently reported reduction products of nitrobenzene [methyl phenyl carbamate (MPC), N,N′‐diphenylurea (DPU), aniline, azobenzene (Azo) and azoxybenzene (Azoxy)], large quantities of oxidation products of methanol were co‐produced (dimethyl carbonate (DMC), dimethyl oxalate (DMO), methyl formate (MF), H₂O, and CO). From these observations, it is concluded that several catalytic processes operate simultaneously, and are coupled via common catalytic intermediates. Starting from a P₂Pd⁰ compound formed in situ, oxidation to a palladium imido compound P₂Pd^II?NPh, can be achieved by de‐oxygenation of nitrobenzene 1) with two molecules of CO, 2) with two molecules of CO and the acidic protons of two methanol molecules, or 3) with all four hydrogen atoms of one methanol molecule. Reduction of P₂Pd^II?NPh to P₂Pd⁰ makes the overall process catalytic, while at the same time forming Azo(xy), MPC, DPU and aniline. It is proposed that the Pd–imido species is the central key intermediate that can link together all reduction products of nitrobenzene and all oxidation products of methanol in one unified mechanistic scheme. The relative occurrence of the various catalytic processes is shown to be dependent on the characteristics of the catalysts, as imposed by the ligand structure.     

Fe3O4‐SAHPG‐Pd0 nanoparticles: A ligand‐free and low Pd loading quasiheterogeneous catalyst active for mild Suzuki–Miyaura coupling and C?H activation of pyrimidine cores

This paper reports a green magnetic quasiheterogeneous efficient palladium catalyst in which Pd⁰ nanoparticles have been immobilized in self‐assembled hyperbranched polyglycidole (SAHPG)‐coated magnetic Fe₃O₄ nanoparticles (Fe₃O₄‐SAHPG‐Pd⁰). This catalyst has been used for effective ligandless Pd catalyzed Suzuki–Miyaura coupling reactions of different aryl halides with substituted boronic acids at room temperature and in aqueous media. Herein, SAHPG is used as support; it also acts as a reducing agent and stabilizer to promote the transformation of Pd^II to Pd⁰ nanoparticles. Also, this environmental friendly quasiheterogeneous catalyst is employed for the first time in the synthesis of new pyrimido[4,5‐b]indoles via oxidative addition/C? H activation reactions on the pyrimidine rings, which were obtained with higher yield and faster than when Pd(OAc)₂ was used as the catalyst. Interestingly, the above‐mentioned catalyst could be recovered in a facile manner from the reaction mixture by applying an external magnet device and recycled several times with no significant decrease in the catalytic activity.     

Is PdII‐Promoted σ‐Bond Metathesis Mechanism Operative for the PdPEPPSI Complex‐Catalyzed Amination of Chlorobenzene with Aniline? Experiment and Theory

Reduction of the Pd?PEPPSI precatalyst to a Pd⁰ species is generally thought to be essential to drive Buchwald–Hartwig amination reactions through the well‐ documented Pd⁰/Pd^II catalytic cycle and little attention has been paid to other possible mechanisms. Considered here is the Pd?PEPPSI‐catalyzed aryl amination of chlorobenzene with aniline. A neat reaction system was used in new experiments, from which the potentially reductive roles of the solvent and labile ligand of the PEPPSI complex in leading to Pd⁰ species are ruled out. Computational results demonstrate that anilido‐containing Pd^II intermediates involving σ‐bond metathesis in pathways leading to the diphenylamine product have relatively low barriers. Such pathways are more favorable energetically than the corresponding reductive elimination reactions resulting in Pd⁰ species and other putative routes, such as the Pd^II/Pd^IV mechanism, single electron transfer mechanism, and halide atom transfer mechanism. In some special cases, if reactants/additives are inadequate to reduce a Pd^II precatalyst, a Pd^II‐involved σ‐bond metathesis mechanism might be feasible to drive the Buchwald–Hartwig amination reactions.     

Microwave‐Promoted Palladium(II)‐Catalyzed C?P Bond Formation by Using Arylboronic Acids or Aryltrifluoroborates

The first Pd^II‐catalyzed P arylation has been performed by using palladium acetate, the rigid bidentate ligand dmphen (dmphen=2,9‐dimethyl‐1,10‐phenanthroline), and without the addition of base or acid. Couplings of arylboronic acids or aryl trifluoroborates with H‐phosphonate dialkyl esters were conducted in 30 min with controlled microwave (MW) heating under non‐inert conditions. Aryl phosphites were also synthesized at room temperature with atmospheric air as the sole reoxidant. The arylated phosphonates were isolated in 44–90 % yields. The excellent chemoselectivity of the method was illustrated in the synthesis of a Mycobacterium tuberculosis glutamine synthetase (MTB‐GS) inhibitor. Online ESIMS was used to detect cationic palladium species in ongoing reactions directly, and a catalytic cycle has been proposed based on these results.     

Palladium(II) Acetylide Complexes with Pincer‐Type Ligands: Photophysical Properties,Intermolecular Interactions,and Photo‐cytotoxicity

Two classes of cationic palladium(II) acetylide complexes containing pincer‐type ligands, 2,2′:6′,2′′‐terpyridine (terpy) and 2,6‐bis(1‐butylimidazol‐2‐ylidenyl)pyridine (C^N^C), were prepared and structurally characterized. Replacing terpy with the strongly σ‐donating C^N^C ligand with two N‐heterocyclic carbene (NHC) units results in the Pd^II acetylide complexes displaying phosphorescence at room temperature and stronger intermolecular interactions in the solid state. X‐ray crystal structures of [Pd(terpy)(C≡CPh)]PF₆ ( 1 ) and [Pd(C^N^C)(C≡CPh)]PF₆ ( 7 ) reveal that the complex cations are arranged in a one‐dimensional stacking structure with pair‐like Pd^II⋅⋅⋅Pd^II contacts of 3.349 Å for 1 and 3.292 Å for 7 . Density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) calculations were used to examine the electronic properties. Comparative studies of the [Pt(L)(C≡CPh)]⁺ analogs by ¹H NMR spectroscopy shed insight on the intermolecular interactions of these Pd^II acetylide complexes. The strong Pd−C_carbene bonds render 7 and its derivative sufficiently stable for investigation of photo‐cytotoxicity under cellular conditions.     

Pincer‐Type Heck Catalysts and Mechanisms Based on PdIV Intermediates: A Computational Study

Pincer‐type palladium complexes are among the most active Heck catalysts. Due to their exceptionally high thermal stability and the fact that they contain Pd^II centers, controversial Pd^II/Pd^IV cycles have been often proposed as potential catalytic mechanisms. However, pincer‐type Pd^IV intermediates have never been experimentally observed, and computational studies to support the proposed Pd^II/Pd^IV mechanisms with pincer‐type catalysts have never been carried out. In this computational study the feasibility of potential catalytic cycles involving Pd^IV intermediates was explored. Density functional calculations were performed on experimentally applied aminophosphine‐, phosphine‐, and phosphite‐based pincer‐type Heck catalysts with styrene and phenyl bromide as substrates and (E)‐stilbene as coupling product. The potential‐energy surfaces were calculated in dimethylformamide (DMF) as solvent and demonstrate that Pd^II/Pd^IV mechanisms are thermally accessible and thus a true alternative to formation of palladium nanoparticles. Initial reaction steps of the lowest energy path of the catalytic cycle of the Heck reaction include dissociation of the chloride ligands from the neutral pincer complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Cl)] [X=NH, R=piperidinyl ( 1 a ); X=O, R=piperidinyl ( 1 b ); X=O, R=iPr ( 1 c ); X=CH₂, R=iPr ( 1 d )] to yield cationic, three‐coordinate, T‐shaped 14e^? palladium intermediates of type [{2,6‐C₆H₃(XPR₂)₂}Pd]⁺ ( 2 ). An alternative reaction path to generate complexes of type 2 (relevant for electron‐poor pincer complexes) includes initial coordination of styrene to 1 to yield styrene adducts [{2,6‐C₆H₃(XPR₂)₂}Pd(Cl)(CH₂?CHPh)] ( 4 ) and consecutive dissociation of the chloride ligand to yield cationic square‐planar styrene complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(CH₂?CHPh)]⁺ ( 6 ) and styrene. Cationic styrene adducts of type 6 were additionally found to be the resting states of the catalytic reaction. However, oxidative addition of phenyl bromide to 2 result in pentacoordinate Pd^IV complexes of type [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(C₆H₅)]⁺ ( 11 ), which subsequently coordinate styrene (in trans position relative to the phenyl unit of the pincer cores) to yield hexacoordinate phenyl styrene complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(C₆H₅)(CH₂?CHPh)]⁺ ( 12 ). Migration of the phenyl ligand to the olefinic bond gives cationic, pentacoordinate phenylethenyl complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(CHPhCH₂Ph)]⁺ ( 13 ). Subsequent β‐hydride elimination induces direct HBr liberation to yield cationic, square‐planar (E)‐stilbene complexes with general formula [{2,6‐C₆H₃(XPR₂)₂}Pd(CHPh?CHPh)]⁺ ( 14 ). Subsequent liberation of (E)‐stilbene closes the catalytic cycle.     

Supramolecular Polymers Self‐Assembled from trans‐Bis(pyridine) Dichloropalladium(II) and Platinum(II) Complexes

Two structurally similar trans‐bis(pyridine) dichloropalladium(II)‐ and platinum(II)‐type complexes were synthesized and characterized. They both self‐assemble in n‐hexane to form viscous fluids at lower concentrations, but form metallogels at sufficient concentrations. The viscous solutions were studied by capillary viscosity measurements and UV/Vis absorption spectra monitored during the disassembly process indicated that a metallophilic interaction was involved in the supramolecular polymerization process. For the two supramolecular assemblies, uncommon continuous porous networks were observed by using SEM and TEM revealed that they were built from nanofibers that fused and crosslinked with the increase of concentration. The xerogels of the palladium and platinum complexes were carefully studied by using synchrotron radiation WAXD and EXAFS. The WAXD data show close stacking distances driven by π–π and metal–metal interactions and an evident dimer structure for the platinum complex was found. The coordination bond lengths were extracted from fitting of the EXAFS data. Moreover, close Pt^II–Pt^II (Pd^II–Pd^II) and Pt?Cl (Pd?Cl) interactions proposed from DFT calculations in the reported oligo(phenylene ethynylene) (OPE)‐based palladium(II) pyridyl supramolecular polymers were also confirmed by using EXAFS. The Pt^II–Pt^II interaction is more feasible for supramolecular interaction than the Pd^II–Pd^II interaction in our simple case.     

Gold/Palladium Alloy for Carbon–Halogen Bond Activation: An Unprecedented Halide Dependence

New catalytic activity of gold/palladium alloy nanoclusters (NCs) for carbon–halogen bond activation is demonstrated. In the case of an aryl chloride, the inclusion of gold in a bimetallic catalyst is indispensable to achieve the coupling reactions. Gold has the unique effect of stabilizing palladium, such that Pd²⁺ leached from clusters by means of spillover of chloride during oxidative addition. The thus‐formed spillover intermediate further reacts heterogeneously in both Ullmann and Suzuki‐type coupling reactions through a new type of mechanism. In the case of an aryl bromide, Ullmann coupling occurs through the spillover of bromide, similar to that of aryl chloride. However, a significant fraction of palladium also leached, which diminished the Ullmann coupling activity of the aryl bromide and, as a result, the order of reactivity was ArCl>ArBr. With regard to the activation of the C?Br bond towards a Suzuki‐type reaction, the inclusion of a higher gold content in gold/palladium clusters stabilized palladium to prevent the leaching of Pd²⁺ from the clusters by means of spillover of bromide. The spillover intermediate reacts heterogeneously with PhB(OH)₂, palladium‐rich gold/palladium, or pure palladium clusters; the oxidative addition of ArBr favors the extraction of palladium from the clusters, yielding Pd²⁺ intermediates. The extracted intermediates react homogenously (Pd^2+/Pd⁰ catalysis) with PhB(OH)₂, which results in the higher selectivity of the cross‐coupling product. An initial step to observe such unprecedented halide dependency, together with the dynamic behavior of palladium on the surface of gold is the oxidative addition of Ar?X. A detailed insight into the first oxidative addition process was also examined by quantum chemical calculations.