N-heterocyclic Carbene Palladium Complexes Research Articles

Well-Defined Palladium N-Heterocyclic Carbene Complexes: Direct C-H Bond Arylation of Heteroarenes.

A series of palladium N-heterocyclic carbene (NHC) complexes of type trans-{(NHC)PdCl2L} (L = C5H5N, 3-ClC5H4N, and PPh3) (3-5) have been developed as efficient precatalysts for direct C-H bond arylation of various heteroarenes. In particular, an in situ generated new NHC ligand derived from {1,3-di-(2,6-diethylphenyl)acenaphtho[1,2-d] imidazolium} chloride (2) is used for the stabilization of the palladium metal center. Among the screened palladium precatalysts (3-5), the most active PEPPSI themed complex (3) was successfully employed toward direct C-H bond arylation of various heteroarenes and aryl bromides. A range of functional groups on aryl bromides as well as on heteroarenes sustained throughout the standard reaction conditions for easy access of various arylated heterocyclic compounds. Significantly, the utility of the protocol was demonstrated by the effective synthesis of a precursor of raloxifene, a selective estrogen receptor modulator.

Biological Activities of NHC–Pd(II) Complexes Based on Benzimidazolylidene N-heterocyclic Carbene (NHC) Ligands Bearing Aryl Substituents

N-heterocyclic carbene (NHC) precursors (2a–i), their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes (3a–i) and palladium N-heterocyclic triphenylphosphines complexes (4a–i) were synthesized and characterized by elemental analysis and 1H NMR, 13C NMR, IR, and LC–MS spectroscopic techniques. The (NHC)Pd(II) complexes 3–4 were tested against MCF7 and MDA-MB-231 cancer cells, Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans microorganisms, Leishmania major promastigotes and amastigotes, Toxoplasma gondii parasites, and Vero cells in vitro. The biological assays indicated that all compounds are highly active against cancer cells, with an IC50 < 1.5 µg mL−1. Eight compounds proved antibacterial and antileishmanial activities, while only three compounds had strong antifungal activities against C. albicans. In our conclusion, compounds 3 (b, f, g, and h) and 4b are the most suitable drug candidates for anticancer, antimicrobial, and antiparasitical.

N,N′‐bridged binuclear NHC palladium complexes: A combined experimental catalytic and computational study for the Suzuki reaction

This work examines how N‐donor bridged spacer ligands affect N‐heterocyclic carbene (NHC) palladium complexes catalytic activities for Suzuki coupling reaction. Different degrees of structural flexibility binuclear NHC palladium complexes were synthesized. The more flexible nitrogen‐based alkyl chain ligand shows similar performance with cycloamine counterparts in the Suzuki coupling reaction. Suzuki coupling examples were used in air and ambient temperature to reach moderate to completion yields in short time. Density functional theory calculations showed that the chelate effect, associated with a single Pd complex mechanism, plays a fundamental role in the pre‐catalysis stage, supporting a reasonable of the kinetic activity observed experimentally.

New Amphiphilic Imidazolium/Benzimidazolium Calix[4]arene Derivatives: Synthesis, Aggregation Behavior and Decoration of DPPC Vesicles for Suzuki Coupling in Aqueous Media.

In this study, new types of amphiphilic calix[4]arene derivatives bearing N-alkyl/aryl imidazolium/benzimidazolium fragments were designed and synthesized by two step transformation: Regioselective Blanc chloromethylation of distal-di-O-butyl calix[4]arene and subsequent interaction with N-Substituted imidazole/benzimidazole. Critical aggregation concentration (CAC) values were estimated using pyrene fluorescent probe. Obtained macrocycles were found to form submicron particles with electrokinetic potential +44–+57 mV in aqueous solution. For the first time it was found that amphiphilic calixarene causes the fast transformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multilamellar vesicles into unilamellar ones and leads to the ordering of the lipid in membranes at the molar calixarene/DPPC ratio more than 0.07. In situ complexes of calixarene aggregates with Pd(OAc)2 were found to be active in Suzuki–Miyaura coupling of 1-bromo-4-nitrobenzene with phenylboronic acid in water. It was shown that bulky N-substituents of heterocycle decrease the catalytic activity of the aggregates. These result can be assigned to the inhibition effect of Pd(II) complex in situ formation by bulky substituents located on the aggregate surface. Embedding of the most active palladium N-heterocyclic carbene (NHC) complex with methylimidazolium headgroups into DPPC vesicles enhances its catalytic activity in Suzuki–Miyaura coupling.

Synthesis of ferrocenyl imidazolium salts and their novel PEPPSI-type N-heterocyclic carbene (NHC) palladium complexes

The novel PEPPSI-type palladium complexes of ferrocenyl-functionalized N-heterocyclic carbenes (NHCs) with different substituents were synthesized. The synthesis of these ferrocenyl-NHCs ligands involves the reaction of the alcohol 1-(ferrocenyl)ethanol successively with 1-substituted imidazole in glacial acetic acid. Following that, the novel PEPPSI-type NHC palladium complexes were prepared by heating their imidazolium salts with PdCl2, K2CO3 in neat pyridine. In addition, deprotonation of N-ferrocenylethyl-N′-(2,4,6-trimethylphenyl)imidazolium chloride (2a) and then its reaction with S8 gave imidazole-2-thione (5). All ligand precursors and all palladium complexes were characterized by elemental analysis, 1H and 13C NMR, and X-ray diffraction methods for two examples.

Synthesis and characterization of a new bis-NHC palladium complex and its catalytic activity in the Mizoroki–Heck reaction

A new bis- N-heterocyclic carbene palladium complex, (C13H9N2F2)2PdCl2, is synthesized by a three-step reaction and characterized by1H NMR and13C NMR spectroscopy as well as by X-ray crystallography. This new bis- N-heterocyclic carbene palladium complex has excellent stability and is capable of efficiently catalyzing the Mizoroki–Heck coupling reaction of aryl halides with acrylates.

Abnormal N-Heterocyclic Carbene–Palladium Complexes for the Copolymerization of Ethylene and Polar Monomers

Palladium complexes bearing abnormal imidazo[1,5-a]pyridine (aImPy)-based N-heterocyclic carbene ligands were developed for the homopolymerization of olefins and the copolymerization of olefins and...

Nickel(ii) N-heterocyclic carbene complexes as efficient catalysts for the Suzuki—Miyaura reaction

Catalytic activity of nickel(ii) and palladium(ii) N-heterocyclic carbene (NHC) complexes derived from imidazole, benzimidazole, and 1,2,4-triazole was comparatively evaluated in the cross-coupling reactions of aryl halides with arylboronic acids. Readily available nickel bis-NHC complexes (NHC)2NiX2 (X = Cl, Br, or I) exhibited the activity comparable to that of the structurally related palladium complexes and, consequently, can be applied as efficient catalysts for the Suzuki—Miyaura reaction.

Comparison of the catalytic performances of bridged bi-metallic and non-bridged mono-metallic PEPPSI type palladium N-heterocyclic carbene complexes

Palladium-N-heterocyclic carbene complexes are widely investigated catalysts in cross-coupling reactions. However, studies about the catalytic activities of bridged bi-metallic complexes are quite rare. Therefore, in this study, anthracene-substituted one mono-metallic and one bridged bi-metallic PEPPSI-type Pd-NHC complexes were synthesized in order to compare their catalytic activities in Suzuki-Miyaura and Mizoroki-Heck reactions. Both complexes were fully characterized by 1H and 13C NMR, LC-MS, IR spectra and elemental analyses. The results of catalytic reactions clearly revealed that mono-metallic complex performs better catalytic activity than bi-metallic analogue in the use of same amount of palladium.

A new PEPPSI type N-heterocyclic carbene palladium(II) complex and its efficiency as a catalyst for Mizoroki-Heck cross-coupling reactions in water

A new air and moisture stable PEPPSI (PEPPSI: pyridine-enhanced pre-catalyst preparation, stabilisation, and initiation) themed palladium N-heterocyclic carbene (NHC) complex [Pd(L)Br2(Py)] (1) [L: 2-flurobenzyl)-1-(4-methoxyphenyl)-1H-imidazolline-2-ylidene] was synthesized and characterized. The structure of complex 1 was determined by X-ray single-crystal analysis. The palladium center in 1 adopted a square planar geometry with carbene and pyridine ligands occupying the mutual trans position. The complex 1 was employed to catalyze the Mizoroki-Heck cross-coupling reactions of aryl bromides/iodides with styrene in water. To the best of our knowledge, this is the first report where a Pd-PEPPSI catalyst was successfully employed in aqueous-phase Mizoroki-Heck reaction. Good to excellent yields of cross-coupling products were obtained with a range of representative aryl bromides/iodides under relatively mild conditions (100 °C, 1 mol% of 1). A new palladium PEPPSI complex was synthesized, characterized and evaluated as catalyst for the Mizoroki-Heck reaction in aqueous medium. Both electron-donating and electron-withdrawing aryl halides (bromides and iodides) reacted with styrene to give corresponding coupling products in moderate to excellent yields.

Hydrogel supported vinylimidazole based PEPPSI-Pd-NHC catalysts: The catalytic activities in Heck and Suzuki-Miyaura coupling reactions

Increasing environmental awareness and limited raw material resources have increased the importance of catalysts by leading to green technology. For this purpose, there is a need for efficient, new, selective, reusable, environmentally friendly catalysts and catalytic systems. In this study, PEPPSI (pyridine enhanced precatalyst preparation, stabilization, and initiation) type and vinylimidazole (VI) based palladium complexes of N-heterocyclic carbenes (PEPPSI-Pd-NHCs) which have catalytic activity in homogeneous Suzuki and Heck reactions were prepared. To obtain environmentally safe polymeric heterogeneous catalysts, this novel PEPPSI-Pd-NHC complexes were polymerized with Acrylamide (AAm) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) by free radical polymerization. Characterization of PEPPSI-Pd-NHC complexes and polymer supported catalysts were made by using various elemental and structural analyses techniques. The synthesized polymeric supported heterogeneous catalysts have high activity, stability and reusability for Suzuki and Heck reaction of aryl bromides in aqueous media.

Synthesis of [PdBr2(Benzimidazole-2-Ylidene)(Pyridine)] Complexes and Their Catalytic Activity in the Direct C-H Bond Activation of 2-Substituted Heterocycles

A series of unsymmetrical 1,3-disubstituted benzimidazolium chlorides 2a-f having two nitrogen atoms substituted by various alkyl groups were synthesized as N-heterocyclic carbene (NHC) precursors in high yields. The benzimidazolium salts readily converted into the corresponding PEPPSI-type palladium–NHC complexes 3a-f (PEPPSI = pyridine-enhanced precatalyst preparation, stabilization, and initiation). The structures of all compounds have been characterized by 1 H NMR, 13 C NMR, and IR spectroscopy, as well as X-rays ( 3a, 3d and 3e ) techniques, which support the proposed structures. Next, the palladium-NHC-PEPPSI complexes were used as catalysts in the direct C(5)-arylation of 2-acetyl furan and 2-acetylthiophene with various aryl bromides. These complexes exhibited moderate to high catalytic activities and gave C-H activation selectively at the C(5)-position of 2-acetylfuran and 2-acetylthiophene.

Stereoelectronic Properties of 1,2,4-Triazole-Derived N-heterocyclic Carbenes - A Theoretical Study

Stereoelectronic Properties of 1,2,4-Triazole-Derived N-heterocyclic Carbenes - A Theoretical Study

N-heterocyclic carbene palladium complexes with different N-coordinated ligands: Comparison of their catalytic activities in Suzuki-Miyaura and Mizoroki-Heck reactions

In this paper, we have reported the synthesis and catalytic activities of four new anthracene substituted imidazole-based palladium N-heterocyclic carbene complexes. The synthesized complexes, 2a–d, were stabilized with different N-heterocycles, namely pyridine, N-methylimidazole, N-vinylimidazole and 4,5-dimethylthiazole, respectively. The complexes were completely characterized using 1H NMR, 13C NMR, IR, LC–MS spectroscopic methods and elemental analyses. The crystal structures of 2a, 2c and 2d were also reported. The catalytic activities of all the complexes were tested for Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions in aqueous medium. According to the results, for the Suzuki-Miyaura reaction, the pyridine bearing complex 2a, and for the Mizoroki-Heck reaction, the 4,5-dimethylthiazole bearing complex 2d were found to be the most active catalysts.

Well‐defined PEPPSI‐themed palladium–NHC complexes: synthesis, and catalytic application in the direct arylation of heteroarenes

In this study, a series of benzimidazolium salts were synthesized as unsymmetrical N‐heterocyclic carbene (NHC) precursors. Benzimidazolium salts were used for synthesis of the PEPPSI (pyridine enhanced precatalyst preparation stabilization and initiation)‐themed, six new Pd‐complexes with the general formula [PdX2(NHC)(pyridine)]. The structures of all compounds were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and FT‐IR. The more detailed structural characterization of four of the complexes was determined by single‐crystal X‐ray diffraction study. The catalytic activities of all Pd‐complexes were evaluated in the direct arylation of the 2‐acetylfuran and 2‐acetylthiophene with aryl bromides in the presence of 1 mol% catalyst loading.

Palladium NHC complexes with benzimidazolium biphenyl ligands: Synthesis, structure, spectral characterization and their application in Suzuki-Miyaura reactions

Synthesis of biphenyl appended benzimidazolium N-heterocyclic carbene (NHC) L1,2H2•X2 ligands, Silver benzimidazolium complex (L1Ag)·(PF6) 1 and Palladium complexes [L1Pd(H3C–CN)(Cl)]·(PF6) 2, [L1PdCl2] 3, [L1PdBr2] 4, [L2PdI2] 5 are reported. All complexes (1–5) are characterized by NMR, ESI-MS, elemental analysis and single crystal XRD. Complex 1 serves as an efficient NHC transfer agent for the preparation of complex 2. Treatment of complex 2 with AgPF6 in DCM solvent resulted in complex 3. Complexes 4 and 5 were prepared by direct metallation method. Complex 1 exists as monomer with Silver in slightly bent geometry. Complexes 2, 3, 4 and 5 are obtained with Palladium in distorted square-planar geometry. All Palladium complexes (2–5) are employed as catalysts in well known Suzuki-Miyaura cross-coupling reaction especially in water.

New morpholine-liganded palladium(II) N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure, and DNA-binding studies.

A series of the morpholine-liganded palladium(II) complexes (1a-e) bearing N-heterocyclic carbene (NHC) functionalized by benzonitrile were synthesized. These complexes were synthesized from (NHC)Pd(II)(pyridine) complexes (PEPPSI) and morpholine. The new complexes were fully characterized by using 1 H NMR, 13 C NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Single-crystal X-ray diffraction was used to determine the structure of a derivative. The DNA-binding studies of the new (NHC)Pd(II)morpholine complexes were examined using the pBR322 plasmid. The 2,4,6-trimethylbenzyl derivative compound has the most DNA binding activity. In addition, for the 3-methylbenzyl derivative compound, oxidation effects were observed at concentrations higher than 100 µg/ml. Also, the molecular and crystal structures of the complex 3-methylbenzyl derivative compound were recorded by using a single-crystal X-ray diffraction method.

Directed C-H Halogenation Reactions Catalysed by PdII Supported on Polymers under Batch and Continuous Flow Conditions.

A new generation of N-heterocyclic carbene palladium(II) complexes containing vinyl groups in different positions in the backbone of the N-heterocycle have been developed. The fully characterised monomers were copolymerised with divinylbenzene to fabricate robust polymer supported NHC-PdII complexes and these polymers were applied as heterogeneous catalysts in directed C-H halogenation of arenes with a pyridine-type directing group. The catalysts demonstrated medium-high catalytic activity with up to 90 % conversion and 100 % selectivity in chlorination. They are heterogeneous and recyclable (at least six times) with no significant leaching of palladium in batch mode catalysis. The best catalyst was also applied under continuous flow conditions where it disclosed an exceptional activity (90 % conversion) and 100 % selectivity for the mono-halogenated product for at least six days, with no leaching of palladium, no loss of activity and an ability to maintain the original oxidation state of PdII .

Direct C-H bond (Hetero)arylation of thiazole derivatives at 5-position catalyzed by N-heterocyclic carbene palladium complexes at low catalyst loadings under aerobic conditions

A highly efficient and practical protocol has been developed for the synthesis of 5-(hetero)arylated thiazole derivatives via an N-heterocyclic carbene palladium (Pd-NHC) complex catalyzed direct C-H arylation reaction. Utilization of this methodology, the arylation of substituted thiazoles with (hetero)aryl bromides efficiently proceeded at low catalyst loading (0.1–0.05 mol%) and under aerobic conditions. A variety of (hetero)aryl bromides, even some strongly deactivated or highly congested (hetero)aryl bromides, with a broad range of functional groups were compatible under the optimal reaction conditions. In all cases, the target products were afforded in moderate to quantitative yields.

Stepwise Synthesis of Tetra-imidazolium Macrocycles and Their N-Heterocyclic Carbene Metal Complexes.

A modular stepwise synthetic method has been developed for the preperation of tetra-imidazolium macrocycles. Initially a series of three bis(imidazolylmethyl)benzene precursors were alkylated with 1,2-dibromoethane to produce the corresponding bis-bromoethylimidazolium bromide salts. In the second step the bis-bromoethylimidazolium bromide salts were reacted with selected bis(imidazolylmethyl)benzene molecules to produce a series of two symmetrical and three asymmetrical tetra-imidazolium macrocycles. These tetra-imidazolium salts act receptors for anions and 1H-NMR titration studies were used to determine the association constants between two of the macrocycles and the halide anions chloride, bromide and iodide. The tetra-imidazolium salts are precursors for N-heterocyclic carbene (NHC) ligands and the corresponding silver(I), gold(I), and palladium(II) NHC complexes have been prepared. Varied structures were obtained, which depend on the chosen macrocyclic ligand and metal ion and in the case of the coinage metals Ag(I) and Au(I), mono, di, and hexanuclear complexes were formed.