Pyridine Enhanced Precatalyst Preparation Stabilization And Initiation Research Articles

Synthesis, crystal structure, and DFT studies of NHC mediated Pd-PEPPSI complex: Application for Suzuki reaction

A novel air and moisture resistant Pd-PEPPSI (pyridine-enhanced precatalyst preparation, stabilization, and initiation) complex was synthesized via the reaction of benzimidazolium salt, PdCl2, KBr, K2CO3, and pyridine. The structure was characterized by spectroscopic methods such as 1H and 13C NMR, FT-IR, UV–vis. and single X-ray diffraction techniques. In order to evaluate the synthesized Pd complex in a detailed manner in terms of structural, bonding, electronic, and thermodynamic characteristics, DFT-based calculations were carried out at the B3LYP/6-311++G (d, p)/LANL2TZ theory level. Natural bond orbital (NBO) analysis was implemented to provide more insights about the possible donor-acceptor interactions and types of hybridization. Also, TD-DFT calculations were performed to rationalize the nature of the observed electronic transitions. The complex showed high catalytic activity in the Suzuki–Miyaura cross coupling of aryl chlorides with phenylboronic acid. Aryl chlorides bearing either electron- donating or withdrawing substituents afforded a wide range of biaryl derivatives that were isolated in the range of 55–97 % yields (7 examples). The reactions were carried out at very low catalyst loading (0.25 mol%) in the presence of air using a green water-based solvent (ipr:H2O/ 1:3). The palladium complex was found to be efficient for the coupling of aryl chlorides with arylboronic acids under aerobic conditions, affording the corresponding biaryls in high yields.

Pd–PEPPSI-type expanded ring N-heterocyclic carbene complexes: synthesis, characterization, and catalytic activity in Suzuki–Miyaura cross coupling

ABSTRACT In this work, we synthesized a series of six unsymmetrical benzimidazolium salts 2 and their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)]. All the products were isolated in satisfactory yields (75-85%). The synthesis of these novel palladium PEPPSI complexes involved in reacting NHC precursors with PdCl2 in pyridine at 60°C in the presence of excess K2CO3. The structures of all compounds have been characterized by 1H NMR, 13C NMR, HRMS and IR spectroscopy, as well as elemental analysis techniques, which support the proposed structures. The catalytic activity of the six complexes was assessed in the Suzuki-Miyaura cross-coupling of phenylboronic acid and aryl halides. The reactions required only a low catalyst loading (0.1 mol%) and were carried out under mild aerobic conditions in a green, water-based solvent mixture.

Palladium(ii) complexes bearing mesoionic carbene ligands: catalytic application in domino Sonogashira coupling/cyclization reactions for one-pot synthesis of benzofuran and indole derivatives.

Bioactive heterocycles such as benzofuran and indole derivatives were synthesized from commercially available 2-iodoarenes and alkynes via domino Sonogashira coupling followed by cyclization reaction using well-defined palladium PEPPSI (Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation) complexes (2a and 2b). These reactions tolerate a variety of 2-iodoarenes and diversely substituted terminal alkynes, resulting in the corresponding product in moderate to good yields in an open-air atmosphere. In particular, two palladium(ii) PEPPSI complexes 2a and 2b were synthesized in good yields from the reaction of corresponding 1,2,3-triazol-5-ylidene (MIC: mesoionic carbene), PdCl2, KI, and K2CO3 in pyridine at 110 °C and structurally characterized by various spectroscopic techniques including NMR spectroscopy, IR spectroscopy, HRMS and elemental analysis studies. Complex 2b is also characterized by X-ray crystallography.

A new air-stable Pd-PEPPSI N-heterocyclic carbene complex: Synthesis, structure, computational and catalytical studies

In this work, we have synthesized a new, air and moisture stable, Pd-PEPPSI (pyridine enhanced pre-catalyst preparation, stabilization and initiation) complex, [PdBr2(NHC)Py] (NHC is 3-benzyl-1-(4-methoxyphenyl)-1H-imidazolline-2-ylidiene) and successfully employed as catalyst under mild conditions (35 °C, 0.5 mol% Pd loading) Suzuki-Miyaura cross-coupling reactions of aryl halides with aryl boronic acids in aqueous isopropanol. A wide range of aryl bromides / iodides were effectively utilized as coupling partners with arylboronic acids to afford corresponding biaryls in moderate-to-excellent yields. The complex was characterized by ESI-MS, 1H and 13C NMR spectroscopy and the molecular structure was determined by X-ray single crystal analysis. In order to gain more insight about structure, bonding and electronic properties, density functional theory (DFT) studies were performed. Moreover, TDDFT calculations were also performed to interpret the observed electronic absorption bands in the UV-VIS spectra. A good agreement between experimental and theoretical data was observed.

Antioxidant activity, enzyme inhibition, electrochemical and theoretical evaluation of novel PEPPSI type N-heterocyclic carbene complexes

N-Heterocyclic carbenes have attracted attention due to their strong sigma-donor and weak pi-acceptor properties since they were first isolated. Pyridine is also found in many natural products and is included in the content of many pharmaceutical molecules. Palladium complexes containing two halogens, a pyridine and an N-heterocyclic carbene have been identified as PEPPSI (Pyridine-Enhanced Precatalyst Preparation Stabilization and Initiation). Although Alzheimer Disease is thought to be affected by environmental and genetic factors, it has not been fully elucidated. There are various mechanisms used to explain the pathogenesis of this disease which guide the design of new drugs. In Alzheimer Disease cases, acetylcholinesterase activity decreases while butyrylcholinesterase increases and disproportionate reactive oxygen species is also recorded. So, the drug used in Alzheimer Disease treatment must have more than one function, that is, the molecule is expected to be effective in both acetylcholinesterase/butyrylcholinesterase balance and antioxidant activity. In this study, PEPPSI type complexes were synthesized and characterized. The structural, electronic, and reactivity properties of the molecules were analyzed by DFT-based calculation methods and Koopman’s Theory. The inhibition activities against acetylcholinesterase, butyrylcholinesterase and tyrosinase were also analyzed, and the antioxidant activity of the molecules were investigated. The inhibition and the activity details of the molecules were also evaluated by molecular docking methods.

Synthesis of PdII Triazolylidene Complexes via an Unusual Csp2‐Csp2 Decoupling Reaction: Applications in α‐Arylation of Amide and Suzuki‐Miyaura Coupling Reactions

AbstractMononuclear PdII complexes bearing mixed MIC/Py/PPh3 donor set ligands are presented starting from a bis‐triazolium salt featuring 4,4’‐substitution pattern of central biphenyl ring. The mononuclear PEPPSI (pyridine enhanced precatalyst preparation, stabilization and initiation) type complexes bearing triazolylidene donor ligand have been synthesized via an unusual Csp2‐Csp2 decoupling reaction. The complexes have been characterized by 1H, 13C{1H} NMR spectroscopy and mass spectrometry. Two of the complexes have also been structurally characterized by single crystal XRD. All the complexes appeared as active precatalysts in α‐arylation of amide and Suzuki‐Miyaura coupling reactions. Catalytic outcomes clearly indicate the superior activities of the PdII complexes with mixed MIC/PPh3 donor set ligands compared to the corresponding PEPPSI type complexes in α‐arylation of oxindole.

Synthesis and characterization of novel PEPPSI type bicyclic (alkyl)(amino)carbene (BICAAC)-Pd complexes

A series of bicyclic alkylamino carbenes (BICAAC) (where N-aryl = dipp, mes, 2,6-dimethyl-4-(dimethylamino)phenyl, 5a–d) and their novel air- and moisture-resistant pyridine (pyridine, 4-dimethylaminopyridine) containing palladium Pd(II) complexes (6a–e) were synthetized and characterized. As novel examples of the PEPPSI (“pyridine enhanced precatalyst preparation stabilization and initiation”)-Pd compounds, the reported complexes have shown high activity in Mizoroki–Heck coupling reaction even at as low as 100 ppm loading (TON up to 10000). Kinetic studies revealed that reactions carried out in the presence of elemental mercury resulted decrease in activity. It indicates that the coupling reaction may have both molecular and Pd(0)-mediated catalytic paths.

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.

PEPPSI complexes as potential prodrugs: enzyme inhibition, antioxidant activity, electrochemical characterization, molecular docking analysis.

In this study, enzyme inhibition and antioxidant activity analyzes of previously characterized pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-type Palladium(II) complexes with benzimidazole-type ligands {dichloro[L]pyridine palladium(II), L1: 1-(2-methyl-2-propenyl)-3-[benzylbenzimidazole]-2-ylidene, L2: 1-(2-methyl-2-propenyl)-3-[4-chloro benzylbenzimidazole]-2-ylidene, L3: 1-(2-methyl-2-propenyl)-3-[3-methylbenzylbenzimidazole]-2-ylidene, L4: 1-(2-methyl-2-propenyl)-3-[3,4,5-thrimethoxybenzylbenzimidazole]-2-ylidene, L5: 1-(2-methyl-2-propenyl)-3-[3-naphthylbenzylbenzimidazole]-2-ylidene, L6: 1-(2-methyl-2-propenyl)-3-[anthracen-9-ylmethylbenzimidazole]-2-ylidene} were performed and evaluated as potential drugs for neurodegenerative disorders such as Alzheimer disease and Parkinson disease. Inhibition of tyrosinase enzyme of N-heterocyclic carbenes (NHC) complexes was determined for the first time in literature. Chelating activities of the complexes were determined and compared with EDTA. Electrochemical characterization was performed using cyclic voltammetry method. Moreover, global reactivity descriptors and electronic transitions were evaluated by DFT/TDDFT methods and molecular docking interactions with human acetylcholine esterase, human butyrylcholine esterase and oxidoreductase were studied.

PEPPSI type Pd(II)NHC complexes bearing chloro-/fluorobenzyl group: Synthesis, characterization, crystal structures, α-glycosidase and acetylcholinesterase inhibitory properties

This work reported the synthesis of a new PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) type Pd(II)N-heterocyclic carbene (NHC) complexes bearing halo-benzyl (4-florobenzyl and 2-chloro-4-florobenzyl) group. These new complexes were synthesized from the florobenzyl / chlorofluorobenzyl substituted benzimidazolium salts, PdCl2 and pyridine. Characterizations of all the synthesized complexes were done using elemental analysis, 1H NMR, 13C NMR and FT-IR spectroscopy techniques. The molecular and crystal structures of the new PEPPSI type Pd(II)NHC complexes were determined by single-crystal X-ray diffraction method. X-ray studies show that molecular structures of three complexes comprise a palladium(II) atom with a slightly distorted square-planar coordination environment. These synthesized salts were found to be effective inhibitors for the α-glycosidase, and acetylcholinesterase (AChE) enzyme with Ki values in the range of 27.36 ± 5.06–124.88 ± 18.05 µM for α-glycosidase, and 0.78 ± 0.11–4.34 ± 1.02 µM for AChE, respectively. The significant group of drugs currently utilized for the therapy of Alzheimer's disease (AD) is acetylcholinesterase/cholinesterase inhibitor compounds. The first cholinesterase inhibitor licensed for symptomatic therapy of AD was tacrine. Inhibition acts of α-glycosidase enzyme by inhibitors tend to slow the breakdown and release of sugar molecules into the bloodstream and can be utilized as therapeutic factors in the therapy of obesity and diabetes.

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.

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.

New Pd-PEPPSI complexes bearing meta-cyanobenzyl-Substituted NHC: Synthesis, characterization, crystal structure and catalytic activity in direct C–H arylation of (Hetero)arenes with aryl bromides

The prestige of the PEPPSI (Pyridine-Enhanced Precatalyst Preparation Stabilization and Initiation) complexes in organometallic chemistry is increasing day by day. Herein, the well-defined seven meta-cyanobenzyl-substituted N-heterocyclic carbene (NHC)–Pd(II)-pyridine (Pd-PEPPSI) complexes were synthesized using palladium acetate, which unlike general procedure is a more economical method than palladium chloride. The new Pd-PEPPSI complexes were obtained from the reaction of the cyanobenzyl substituted NHC precursors and palladium acetate in pyridine. The new complexes have been fully characterized by 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. Also, the X-ray diffraction method was used to determine the single-crystal structure of a complex. The Pd-PEPPSI complexes have been examined as catalysts in the direct arylation reactions of 2-n-butylfuran and 2-n-butylthiophene with aryl bromide. All complexes have demonstrated excellent activity in these reactions. The Molecular and crystal structure of one of the cyanobenzyl substituted Pd-PEPPSI complexes was determined by the single-crystal X-ray diffraction method. X-ray diffraction studies show that the molecular structure adopts a slightly distorted square-planar geometry with the palladium (II) center.

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.

1,2,3-Triazol-5-ylidene bearing a pyridine auxiliary based bidentate PEPPSI type palladium(II) complex: Synthesis, structure, and application in the direct arylation of pyridine N-oxide

A novel PEPPSI (pyridine enhanced precatalyst preparation stabilization and initiation) type palladium(II) complex has been synthesized and fully characterized by NMR, HR-MS, as well as elemental analysis. The molecular structure was finally confirmed by single crystal X-ray diffraction, and it revealed that the pyridyl-armed 1,2,3-triazole ligand is coordinated to the palladium in bidentate fashion. This air and moisture insensitive complex has proven to be a suitable catalyst for the arylation of pyridine N-oxides and 2-bromopyrroles with a broad functional group tolerance, demonstrating that the robustness and high efficiency of our complex.

Enhanced π-back-donation resulting in the trans labilization of a pyridine ligand in an N-heterocyclic carbene (NHC) PdII precatalyst: a case study.

The molecular structure of the benzimidazol-2-ylidene-PdCl2-pyridine-type PEPPSI (pyridine-enhanced precatalyst, preparation, stabilization and initiation) complex {1,3-bis[2-(diisopropylamino)ethyl]benzimidazol-2-ylidene-κC2}dichlorido(pyridine-κN)palladium(II), [PdCl2(C5H5N)(C23H40N4)], has been characterized by elemental analysis, IR and NMR spectroscopy, and natural bond orbital (NBO) and charge decomposition analysis (CDA). Cambridge Structural Database (CSD) searches were used to understand the structural characteristics of the PEPPSI complexes in comparison with the usual N-heterocyclic carbene (NHC) complexes. The presence of weak C-H...Cl-type hydrogen-bond and π-π stacking interactions between benzene rings were verified using NCI plots and Hirshfeld surface analysis. The preferred method in the CDA of PEPPSI complexes is to separate their geometries into only two fragments, i.e. the bulky NHC ligand and the remaining fragment. In this study, the geometry of the PEPPSI complex is separated into five fragments, namely benzimidazol-2-ylidene (Bimy), two chlorides, pyridine (Py) and the PdII ion. Thus, the individual roles of the Pd atom and the Py ligand in the donation and back-donation mechanisms have been clearly revealed. The NHC ligand in the PEPPSI complex in this study acts as a strong σ-donor with a considerable amount of π-back-donation from Pd to Ccarbene. The electron-poor character of PdII is supported by π-back-donation from the Pd centre and the weakness of the Pd-N(Py) bond. According to CSD searches, Bimy ligands in PEPPSI complexes have a stronger σ-donating ability than imidazol-2-ylidene ligands in PEPPSI complexes.

Novel morpholine liganded Pd-based N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure, antidiabetic and anticholinergic properties

This study involves the synthesis of novel N-heterocyclic carbene (NHC)PdX2(morpholine) complexes (1a–i). These Pd-based complexes are synthesized from pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) complexes and morpholine. The new complexes were characterized by spectroscopy (IR, 1H and 13C NMR) techniques. Also, the crystal structures of 1b and 1f were obtained by utilizing the single-crystal X-ray diffraction method. The synthesized compounds in this study were investigated for their inhibition action against equin serum butyrylcholinesterase (BChE) and Electrophorus electricus acetylcholinesterase (AChE) as the capability drug aims for Alzheimer’s disease (AD). These novel morpholine liganded Pd-based N-heterocyclic complexes were good inhibitors of BChE, α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and AChE, with Ki values in the range of 10.77 ± 1.01–45.86 ± 5.65 µM for hCA I, 25.42 ± 5.18–57.82 ± 3.01 µM for hCA II, 12.26 ± 3.32–50.36 ± 6.19 µM for α-glycosidase, 9.97 ± 1.26–60.75 ± 15.98 µM for BChE, and 10.28 ± 1.55–30.12 ± 3.22 µM for AChE. The inhibition of the α-glycosidase enzyme, an important carbohydrate hydrolyzing catalyst, could be used as one of the efficient methodologies in both treating and preventing diabetes by controlling the suppressing postprandial hyperglycemia and postprandial glucose amounts.

2‐Hydroxyethyl‐Substituted Pd‐PEPPSI Complexes: Synthesis, Characterization and the Catalytic Activity in the Suzuki‐Miyaura Reaction for Aryl Chlorides in Aqueous Media

AbstractIn recent years, PEPPSI (Pyridine‐Enhanced Precatalyst Preparation Stabilization and Initiation) complexes have attracted attention in organometallic chemistry. This study contains the synthesis of the 2‐hydroxyethyl‐substituted Pd‐PEPPSI complexes and their catalytic activity in the Suzuki‐Miyaura reaction aryl chlorides in aqueous media. The Pd‐PEPPSI complexes have been prepared from the 2‐ hydroxyethyl‐substituted N‐heterocyclic carbene (NHC) precursors, palladium chloride and 3‐chloropyridine. The Pd‐PEPPSI complexes have been characterized by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. The Pd‐PEPPSI complexes have been examined as catalysts in the Suzuki‐Miyaura reactions in aqueous media with arylboronic acid derivatives. Also, they have demonstrated excellent activity in these reactions. Molecular and crystal structure of one of the 2‐hydroxyethyl substituted Pd‐PEPPSI complex was determined by single crystal X‐ray diffraction method. X‐ray studies show that the molecular structure adopts a slightly distorted square‐planar geometry with the palladium (II) center.

Adamantane, Irene, Naftazone and Pyridine-Enhanced Precatalyst Preparation Stabilization and Initiation (PEPPSI) Nano Molecules

Adamantane, Irene, Naftazone and Pyridine-Enhanced Precatalyst Preparation Stabilization and Initiation (PEPPSI) Nano Molecules

N-Heterocyclic carbene-Pd(II)-PPh3 complexes as a new highly efficient catalyst system for the Sonogashira cross-coupling reaction: Synthesis, characterization and biological activities

A novel series of N-heterocyclic carbene-phosphine palladium(II) complexes has been synthesized and fully characterized by IR, 1H NMR, 13C NMR, and 31P NMR spectroscopies, and elemental analysis. The new N-heterocyclic carbene (NHC)-phosphine palladium(II) complexes 3a–h have been easily prepared by the reaction of the corresponding PEPPSI (pyridine-enhanced precatalyst preparation stabilization and initiation) complexes 2a–h and triphenylphosphine in dichloromethane in high yields. These complexes were applied as catalyst precursors which efficiently catalyzed Sonogashira reactions between aryl bromides and phenylacetylene to afford the corresponding products in good yields. The bulky NHC-Pd-PPh3 complexes 3 were tested against Gram-positive and Gram-negative bacteria to study their biological activity. All the complexes exhibit antibacterial against these organisms. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a and 3b exhibited moderate activity at 100 μg mL−1 and product 3b is the most active.