Pd-NHC Complexes Research Articles

Synthesis, characterization and the catalytic application of the N-heterocyclic carbene-PdCl2-cyanopyridine complexes

Six monoligated N-heterocyclic carbene-PdCl2-cyanopyridine complexes were prepared (N-heterocyclic carbene = NHC). X-ray single crystal diffraction analysis indicated that the complexes showed mononuclear Pd–NHC structures with two chlorides and the N-donor from cyanopyridine as ancillary ligands. The lengths of the Pd–C bonds in all complexes were 1.959(5)–1.976(3) Å, comparable to those found in the corresponding Pd–NHC catalysts. The catalytic activities of the well-defined Pd–NHC complexes have been evaluated with respect to the Hiyama cross-coupling reactions of aryl trialkoxysilanes with aryl chlorides. With 1.0 mol% Pd-catalyst, all synthesized palladium compounds have shown moderate to good catalytic activities for the coupling reactions.

Synthesis of amide functionlized bidentate NHC-Pd complex for application as catalyst in Suzuki‐Miyaura cross-coupling, in distilled water, under mild reaction conditions

An amide functionlized bidentate NHC-Pd complex was successfully prepared by a facile solvothermal methodology from a bridged bis-benzimidazolium chloride and K2PdCl4. The new bidentate NHC-Pd complex has been effectively applied as catalyst in Suzuki-Miyaura cross-coupling reactions of aryl halides with arylboronic acids in distilled water (yields up to 99.0%). The bridged bis-benzimidazolium ligand from the Pd complex, bearing the amide functional groups on the nitrogen atom, showed to distinctly influence the electronic and steric effects on the catalytic process. The potential of application of the new NHC-Pd catalyst in diverse CC bond forming processes, working under environmentally friendly conditions, is further outlined.

Bridged NHC-Pd(II) complexes: Synthesis, DFT calculations, molecular docking, and investigation of catalytic and biological activities

Six palladium(II) (3a-f) complexes of the type [Pd2(μ-Cl)2(NHC)] were prepared by transmetallation of the corresponding Ag-NHC and [PdCl2(CH3CN)2] complexes, and their structures were successfully characterised by 1H NMR, 13C NMR, HRMS, FTIR and elemental analysis. Density functional theory (DFT) calculations were also realised for the complexes. The prepared complexes were assessed for their catalytic activity in the C-H arylation of 2-isobuthylthiazole as well as for their biological activities. As results, these complexes were found to be potent catalysts in the creation of C5-arylated 2-isobuthylthiazole derivatives via C-H bond activation reaction. Furthermore, biological activity analysis revealed that complex 3a exhibits high cytotoxicity towards both human colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) with IC50 values of 4.2 and 9.3 µMmL−1, respectively. Complex 3b also showed antioxidant activity comparable to that of BHT through DPPH and ABTS assays. Both complexes 3d and 3f also showed significant inhibitory activity towards the AChE enzyme with IC50 values of 5.06 and 2.52 µMmL−1, respectively. Finally, all complexes showed excellent antiparasitic activity, with 3b exhibiting strong antileishmanial activity against both L. major promastigotes and amastigotes. The interaction between the most cytotoxic complexes and DNA, envisaged as a potential mechanism of toxicity, was explored by means of docking studies. In summary, these prepared complexes have the potential to serve as potent catalysts for the synthesis of arylated 2-isobutylthiazole and biologically active agents, paving the way for numerous prospects in the fields of medicinal chemistry and organic synthesis.

Synthesis, Molecular Docking, Anti-cholinesterase Activity, Theoretical Investigation, and Catalytic Effect of New Encumbered N-benzyladamantyl Substituted Imidazolidin-2-ylidene Carbene Pd-PEPPSI Complexes

Abstract: This study aimed to describe the preparation of novel PEPPSI type Pd(II)-NHC complexes bearing N-benzyladamantyl substituted imidazolidin-2-ylidene group. All synthesized compounds were characterized by using 1H-NMR and 13C-NMR spectroscopies, FTIR, and elemental analysis techniques. One of the objectives of this study was the synthesis of Pd-NHC complexes with AChE/BChE inhibition activities. Among all the tested compounds, complexes 4b and 4c were found to have the most high potential AChE and BChE inhibitory activities with IC50 values of 21.57 ± 0.23 Mm and 15.78 ± 0.39 Mm, respectively. Conducting molecular docking studies helped us in gathering crucial information about the main binding interactions of inhibitors and enzymes, and the results were in agreement with the biological evaluation. The synthesized Pd-NHC complexes were employed for catalyzing the direct C2- and C5-arylation reaction between aryl (hetero) halide and a variety of heterocyclic systems. In both cases (C2 and C5-arylation), Pd-NHC complexes catalysts provided access to the arylated heterocycles in good to high yields in the presence of 1 mol% catalyst loading at 150°C. The DFT theoretical investigation showed that the Pd-NHC complexes were of ML2X2 type, where the the Pd(II) cation had a square planar geometry. The interaction energies obtained by energy decomposition analysis (EDA) demonstrated that the 4d and 4e complexes were more stable in the presence of more methyl substituents. The chemical indicators demonstrated that the less stable 4c complex was more reactive in regard to the chemical hardness, chemical potential, and electrophilicity values.

Plausible PEPPSI catalysts for direct C-H functionalization of furans and pyrroles

The worth of bi(hetero)arenes in ongoing medicinal and industrial research fields promotes their efficient synthesis by Pd-PEPPSI-bearing NHC spectator ligands encapsulated as site-selective direct C-H functionalization agents. Eight new asymmetric N-heterocyclic carbenes ligands and their plausible pyridine-assisted Pd (II) complexes are reported in this work. The synthesized compounds were thoroughly characterized by respective spectroscopic techniques, such as 1H, 13C, FTIR and elemental analysis. The structures of synthesized pro-ligand salts and complexes were determined by Single Crystal XRD. The on/off mechanism of pyridine assisted Pd-NHC complexes made them the best C-H functionalized catalysts for regioselective C5 arylated products. Five membered heterocyclic compounds such as 2-acetyl furan, furfuryl acetate and 1-methyl-2-pyrrole-carboxylaldehyde were treated with numerous aryl bromides under optimal catalytic reaction conditions. Furfuryl acetate was used for the first time as a substrate in the present research work. Interestingly, all the prepared catalysts possessed essential structural features that facilitated the formation of desired coupled products in quantitative yield with excellent selectivity.

Design, synthesis, characterization, crystal structure, in silico studies, and inhibitory properties of the PEPPSI type Pd(II)NHC complexes bearing chloro/fluorobenzyl group

This work contains synthesis, characterization, crystal structure, and biological activity of a new series of the PEPPSI type Pd(II)NHC complexes [(NHC)Pd(II)(3-Cl-py)]. NMR, FTIR, and elemental analysis techniques were used to characterize all (NHC)Pd(II)(3-Cl-py) complexes. Also, molecular and crystal structures of complex 1c were established by single-crystal X-ray diffraction. Regarding the X-ray studies, the palladium(II) atom has a slightly distorted square-planar coordination environment. Additionally, the enzyme inhibitory effect of new (NHC)Pd(II)(3-Cl-py) complexes (1a-1g) was studied. They exhibited highly potent inhibition effect on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 0.08 ± 0.01 to 0.65 ± 0.06 µM, 10.43 ± 0.98 to 22.48 ± 2.01 µM, 6.58 ± 0.30 to 10.88 ± 1.01 µM and 6.34 ± 0.37 to 9.02 ± 0.72 µM for AChE, BChE, hCA I, and hCA II, respectively). Based on the molecular docking, among the seven synthesized complexes, 1c, 1b, 1e, and 1a significantly inhibited AChE, BChE, hCA I, and hCA II enzymes, respectively. The findings highpoint that (NHC)Pd(II)(3-Cl-py) complexes can be considered as possible inhibitors via metabolic enzyme inhibition.

Pd-NHC complex catalyzed C-H bond activation reactions of caffeine and 2-isobuthylthiazole

A series of new Pd-NHC complexes were synthesized, characterized, and utilized as catalysts on 8-(hetero)arylation of xanthines and C-5 (hetero)arylation of 2-isobuthylthiazole. All the synthesized derivatives were characterized by NMR, Q-TOF-LC/MS, FTIR, and X-ray (for 4a, 5a, and 5b) analysis. In addition, DFT calculations and computational NBO studies for Pd-NHC complexes were examined, and HOMO and LUMO energy levels and electron density of each Pd-NHC complex were defined. 4a-c and 5a-b complexes showed good catalytic activity in C-H bond activation reactions. DFT studies have also been conducted to examine the reaction mechanism following the CMD pathway. Complex 5a was chosen as a representative catalyst for the reaction of unsubstituted phenyl with caffeine and 2-isobuthylthiazole. Although the ΔE values of the complexes are so close, slight difference in the catalytic activity were observed for 4a-c and 5a-b. Since this low ΔE value facilitates the oxidative addition reaction of (hetero)aryl bromides, thanks to this catalytic system, new 8-(hetero)aryl xanthines and 5-(hetero)aryl thiazole derivatives could be synthesized with high yields and low catalyst loading.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

Pd-Nhc Complex Catalyzed C-H Bond Activation Reactions of Caffeine and 2-Isobuthylthiazole

Pd-Nhc Complex Catalyzed C-H Bond Activation Reactions of Caffeine and 2-Isobuthylthiazole

Synthesis of new Pd(NHC)-PEPPSI type complexes as catalysts toward C-C cross-coupling reactions

• A series of palladium- N -heterocyclic carbene complexes were synthesized and characterized. • Pd-NHC complexes used as catalyst the C-C cross-coupling reactions. • They exhibited were found significantly active as catalysts toward these reactions. The goal of our research is to synthesis homogeneous catalysts, for which we take start from two novel precursors of 1-(3-methyloxetane-3-yl)benzimidazole and 5,6-dimethyl-1-((3-methyloxetane-3-yl)benzimidazole. A series of ligands containing 1,3-disubstituted benzimidazolium salts were synthesized from the corresponding precursors to form N-heterocyclic carbene (NHC) ligands. Furthermore, four new Pd(NHC)-PEPPSI type complexes were synthesized from these ligands. The structure elucidation of all the synthesized ligands, and complexes was confirmed by various spectroscopic techniques such as NMR, FT-IR. The compounds 1b, 2b, 3a, 3d were confirmed by the X-ray technique. All these complexes were found significantly active as catalysts toward the C-C cross-coupling reaction.

New benzimidazolium N-heterocyclic carbene precursors and their related Pd-NHC complex PEPPSI-type: Synthesis, structures, DFT calculations, biological activity, docking study, and catalytic application in the direct arylation

New benzhydryl-5,6-dimethyl-(3-methylbenzyl)benzimidazolium salt as N-heterocyclic carbene precursors and their related new Pd-NHC complex PEPPSI-type with the general formula [PdBr2(NHC)(pyridine)] were prepared and theoretically studied. Quantum chemistry computations at the B3LYP/6-311G(d,p)/LANL2DZ level were used to examine the molecular structure, electronic characteristics, and chemical reactivity of the ligand and its Pd complex. Further, the structural characterization of the complex (c) was determined by a single-crystal X-ray diffraction study, which supports the proposed structures and offered a more detailed structural characterization. In addition, their biological activity against.cholinesterase enzymes were also determined. The new compounds were tested against two enzymes (AChE and BChE), furthermore, docking studies were carried out in order to gain a better understanding of the bonding modes of L and COP in the active sites of AChE and BChE enzymes. The new salt and Pd-NHC complex PEPPSI-type were fully characterized by spectroscopic and analytical methods. The new Pd-catalysts based N-heterocyclic carbene ligand PEPPSI-Type was applied by the direct arylation process of five-membered heteroaromatics such as thiophene, and furan derivatives with various (hetero)aryl bromides in the presence of 1 mol% catalyst, using KOAc as a co-catalyst. The results showed that the new Pd-NHC complex is an effective catalyst.

C(sp2)-C(sp2) Suzuki cross-coupling of arylammonium salts catalyzed by a stable Pd–NHC complex

We have developed the Suzuki-Miyaura cross-coupling of aryl ammonium salts via C–N bond activation catalyzed by an easily prepared and bench-stable palladium-N-heterocyclic carbene complex. The reaction proceeded well under mild conditions with phenylboronic acid, pinacol ester or anhydride and provided yields of products up to 97% with good functional group compatibility. The direct arylation of arylamine can be performed by a two-step one-pot process and the protocol can be performed on the gram scale.

Phosphonate functionalized N-heterocyclic carbene Pd(II) complexes as efficient catalysts for Suzuki-Miyaura cross coupling reaction

A N-heterocyclic carbene (NHC) ligand, L1 bearing a pendant phosphonate ester group is used to prepare two new NHC-Pd(II) complexes, [Pd(L1)2I2] (1) and [Pd(L1)(py)I2] (2) (py = pyridine). Hydrolysis of phosphonate ester group in 2 results another Pd(II)-NHC complex, [Pd(L2)(py)I2] (3) where a phosphonic acid group is attached to the NHC ligand L2. All the three complexes are characterized by analytical and spectroscopic studies while the molecular structures of 1-2 are also determined by single crystal X-ray diffraction measurement. The catalytic efficacies of 1-3 in Suzuki-Miyaura cross coupling reactions of aryl halides and aryl boronic acid are investigated. DFT calculations were performed to decipher the role phosphonate ester or phosphonic acid substituents on the catalytic efficacy.

Benzimidazole-functionalized PEPPSI type Pd(II)NHC complexes bearing nitrophenylethyl and hidroxyphenylethyl group: Synthesis, characterization, crystal structure and it's catalytic activity on direct arylation reaction

This study contains synthesis, characterization, crystal structure, and catalytic activity of the new two series PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) type Pd(II)NHC complexes nitrophenylethyl and hidroxyphenylethyl groups. All complexes were prepared from the nitrophenylethyl and hidroxyphenylethyl substitute benzimidazolium salts, palladium chloride (PdCl2) and 3-chloropyridine. The structures of all PEPPSI type Pd(II)NHC complexes have been fully characterized by using NMR (1H and 13C), FTIR spectroscopic method, and elemental analysis techniques. Also, the single-crystals of four of these complexes were examined by utilizing by the X-ray diffraction method. Also, the catalytic activity of the nitrophenylethyl and hidroxyphenylethyl substituted benzimidazole-functionalized PEPPSI type Pd(II)NHC complexes on the direct arylation reaction were examined. It has been observed that among these complexes, those bearing electron-donor groups (hydroxyphenylethyl) are more active catalysts than those bearing electron-withdrawing groups (nitrophenylethyl) for direct arylation reactions.

Synthesis, crystal structures and catalytic activities of palladium complexes with coumarin-functionalised N-heterocyclic carbene ligands

In this contribution, we synthesized five new coumarin-functionalised PEPPSI type Pd-NHC complexes in order to examine their catalyst properties. The complexes were synthesized by the reaction of PdCl2 and corresponding benzimidazolium chloride in pyridine in the presence of excess amount of K2CO3. The structures of complexes were fully characterised using NMR and IR spectroscopy, elemental analyses and X-ray diffraction analyses. Crystal structures of four complexes revealed that they have slightly distorted square-planar geometry. Catalytic activities of complexes were tested in Suzuki-Miyaura reaction of phenylboronic acid and aryl bromide derivatives in H2O-DMF solvent system.

Multicomponent Synthesis of Unsymmetrical 4,5-Disubstituted Imidazolium Salts as N-Heterocyclic Carbene Precursors: Applications in Palladium-Catalyzed Cross-Coupling Reactions.

Various novel (a)chiral 4,5-disubstituted 1-aryl-3-alkyl-imidazolium salts were synthesized via the multicomponent reaction of diketone derivatives, sterically congested arylamines, and alkylamines. Moreover, two novel unsymmetrical bulky cycloalkyl-based NHC-Pd complexes proved highly active as catalysts for Suzuki-Miyaura and Negishi cross-coupling reactions.

Synthesis, structures, DFT calculations, and catalytic application in the direct arylation of five-membered heteroarenes with aryl bromides of novel palladium-N-heterocyclic carbene PEPPSI-type complexes

A new series of Pd-catalysts was synthesized and fully characterized via spectroscopic methods and the Pd–NHC complexes were evaluated via the direct arylation process.

Pd/NHC-catalyzed arylsulfonylation of boronic acids: A general and direct protocol to access diarylsulfones

For the first time, robust NHC-Pd complexes have been demonstrated as highly efficient catalysts in the direct arylsulfonylation of boronic acids. Remarkably, a broad number of diaryliodonium salts as powerful electrophilic arylation reagents are well compatible to form functional ortho-substituted diarylsulfones in satisfactory yields. Owing to the stronger σ-donor and weaker π-acceptor properties, the acenaphthoimidazolylidene ligands exhibit higher catalytic activities towards this challenging one-step arylsulfonylation reaction.

The synthesis of new PEPPSI-type N-heterocyclic carbene (NHC)-Pd(II) complexes bearing long alkyl chain as precursors for the synthesis of NHC-stabilized Pd(0) nanoparticles and their catalytic applications

Six new N-heterocyclic carbene (NHC) ligands bearing long-chain alkyl groups on N-atom of 5,6-dimethylbenzimidazole skeleton and their Pd(II) complexes (PEPPSI type) with a close formula of trans-[PdX2(NHC)Py] (X = Cl or Br; Py = pyridine) were successfully synthesized. The yielded NHC ligands and their Pd(II) complexes were characterized by elemental analysis, 1H- and 13C NMR, FT-IR spectroscopy, and mass spectroscopy and the molecular structure of 3f was determined by X-ray crystallography. All synthesized NHC-Pd(II) complexes were air-stable both as powder and in solution under ambient conditions, which allow us to test them as catalysts in Suzuki-Miyaura cross-coupling (SMC) reactions and to use them as precursors for the in situ synthesis of NHC-stabilized Pd(0) nanoparticles (NPs) during the dehydrogenation of ammonia borane (AB) in dry tetrahydrofuran solution at room temperature. In this protocol, AB served both as a reducing agent for the reduction of NHC-Pd(II) complexes to yield NHC-stabilized Pd(0) NPs and a chemical hydrogen storage material for the concomitant hydrogen generation. The in situ synthesized NHC-stabilized Pd(0) NPs were characterized by UV–Vis spectroscopy, TEM, and XRD techniques. The catalytic activity of the in situ generated NHC-stabilized Pd(0) NPs in the dehydrogenation of AB was followed by measuring the volume of hydrogen generated versus time at room temperature. Among the five different NHC-Pd(II) complexes, 3c (dichloro[1-octadesyl-3-(2,4,6-trimethylbenzyl)-(5,6-dimethylbenzimidazol-2-ylidene)](pyridine)palladium(II)) yielded the most stable Pd(0) NPs along with the highest catalytic activity in the dehydrogenation of AB (TOF= 37.7 min−1 at 1 eqv. H2 release). The 11B-NMR analysis of the THF solution after the catalytic dehydrogenation of AB revealed the formation of cyclopolyborazane, which is one of the important dehydrocoupling products of AB. Additionally, all NHC-Pd(II) complexes provided high yields in the SMC reactions of phenylboronic acid with various aryl bromides bearing electron-withdrawing or electron-donating groups and even for aryl chlorides bearing electron-withdrawing group at room temperature with the low catalyst loadings. This study revealed that the length of the alkyl chain of NHC ligands has a significant effect on the catalytic activity of the NHC-Pd(II) complexes in the SMC reactions, the longer the alkyl chain on the N atom of NHC ligand, the higher activity of NHC-Pd(II) complex in SMC reactions. It also influences the particle size, morphology and catalytic activity of in situ generated Pd(0) NPs in the dehydrogenation of AB.

Synthesis, characterization, crystal structure and bioactivity properties of the benzimidazole-functionalized PEPPSI type of Pd(II)NHC complexes

Herein, six new benzimidazole-functionalized Pd-based complexes bearing N-propylphthalimide group were synthesized. These new PEPPSI type of Pd(II)NHC complexes (PEPPSI: Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) were prepared from the N-propylphthalimide substituted benzimidazolium salts, palladium chloride (PdCl2) and 3-chloropyridine. The structures of all (NHC)PdX2(3-chloropyridine) complexes have been clearly characterized by using NMR (1H and 13C), FTIR spectroscopic method, and elemental analysis techniques. Also, the structures of three of the (NHC)PdX2(3-chloropyridine) complexes were confirmed by single-crystal X-ray diffraction. Also, novel N-propylphthalimide-substituted (NHC)PdX2(3-chloropyridine) complexes effectively inhibited acetylcholinesterase (AChE), with Ki values in the range of 0.54 ± 0.10 to 3.01 ± 0.63 µM. For butyrylcholinesterase (BChE) was obtained with Ki values in the range of 0.82 ± 0.11 to 5.03 ± 0.86 µM. For α-glycosidase (α-Gly) the most effective Ki values of 1c, 1d, and 1b were with Ki values of 23.83 ± 5.98, 26.04 ± 7.11, and 30.61 ± 3.85 µM, respectively. All novel N-propylphthalimide-substituted PEPPSI complexes and control compounds had almost similar inhibition profiles.