Search

A series of palladium‐N‐heterocyclic carbene complexes (2 a‐e) were synthesized from corresponding N‐heterocyclic carbene precursors (1 a‐e) in good yields. The structural analysis of all novel compounds was done by spectroscopic methods and elemental analysis was also performed to evaluate the purity of the complexes. Further confirmations of complexes 2 a‐d were provided by X‐ray crystallography technique. Under optimized reaction conditions, the catalytic activity of the palladium‐N‐heterocyclic carbene complexes was reviewed by direct arylation of furan‐2‐carboxaldehyde and 1‐methylpyrrole‐2‐carboxaldehyde with varied aryl halides. This arylation showed productive and selective reaction at the C5‐position of heteroaryl derivatives. [ABSTRACT FROM AUTHOR]

Recently, PEPPSI‐type palladium‐complexes bearing N‐heterocyclic carbene (NHC) ligand have commonly been used as the effective catalysts in the direct arylation of heteroaromatic compounds. In most of previous studies catalyzed by such complexes, unsaturated ring carbene ligands such as benzo[d]imidazol‐2‐ylidene and imidazol‐2‐ylidene were used. However, the use of saturated ring carbene ligands such as 4,5‐dihydro‐imidazol‐2‐ylidene has been highly limited. Therefore, in this study, four novel 4,5‐dihydro‐1H‐imidazolium salts were synthesized as saturated ring carbene precursors. Then, well‐defined air‐ and moisture‐stable four novel PEPPSI‐type palladium‐complexes with 4,5‐dihydro‐imidazol‐2‐ylidene ligands were prepared. All synthesized carbene precursors and palladium‐complexes were structurally characterized by different spectroscopic and analytical techniques. Further structural characterization of two of the palladium‐complexes was performed by single‐crystal X‐ray diffraction. Next, the palladium‐complexes were tested in the direct arylation of azoles such as 4,5‐dimethylthiazole and 1‐methyl‐1H‐imidazole with (hetero)aryl halides in presence of 1 mol% catalyst loading at 120°C. The results showed that these novel palladium complexes are effective catalysts. [ABSTRACT FROM AUTHOR]

Amination reactions play a pivotal role in synthetic organic chemistry, facilitating the generation of nitrogen-containing scaffolds with broad applications in drug synthesis, material production, polymer formation, and the generation of amino acids and peptides. Amination offers the potential to fine tune the properties of natural products and produce functional materials for various applications. Palladium N-heterocyclic carbene (Pd–NHC) emerges as an innovative and highly effective catalyst in this context. Under favorable reaction conditions, this robust and simple catalyst efficiently facilitates the synthesis of a diverse range of compounds with varying complexity and utility. Pd–NHC complexes exhibit significant σ-electron donating potential, enhancing the ease of the oxidative addition process in their mechanistic pathway. Their steric topography further contributes to a rapid reductive elimination. These complexes demonstrate remarkable stability, a result of the strong Pd–ligand bond. The wide variety of Pd–NHC complexes has proven highly efficient in catalyzing reactions across a spectrum of complexities, from simple to intricate. The domain of aminations catalyzed by Pd–NHC has undergone significant diversification, presenting new opportunities, particularly in the realms of material chemistry and natural product synthesis. This review outlines the advancements in Pd–NHC-catalyzed amination reactions, covering literature up to date. Palladium (Pd) N-heterocyclic carbenes (NHCs) have amassed high recognition recently. They are efficient complexes with tuneable complexities promoting catalysis significantly. Amination reactions have paved way toward the formation of C–N bonds and, in turn, realizing structurally relevant molecules in organic chemistry. Inspired by these facets, we have tried to encompass in this review, the developments in Pd–NHC-catalyzed amination reactions and carries reports up to date. [ABSTRACT FROM AUTHOR]

A PEPPSI-type imidazolidin-2-ylidene-based palladium(II) complex was prepared according to literature. Detail molecular structure of this complex has been confirmed by X-ray diffraction analysis and supplemented by theoretical calculations. Also, electronic properties of the complex were investigated by UV-Vis spectroscopy. The complex under scrutiny was found to adopt a trans arrangement with square-planar geometry. Furthermore, theoretical structure and spectroscopic data were obtained using density functional theory (DFT/HSEH1PBE) method and SDD basis set, and compared with the experimental data. In general, the theoretical findings were in line with the experimental outcomes. [ABSTRACT FROM AUTHOR]

• A novel air and moisture resistant NHC-based Pd-PEPPSI complex was synthesized. • The structure and properties of the complex were studied in detail both experimental and theoretical. • The complex was successfully screened as catalyst for the Suzuki-Miyaura reaction of phenylboronic acid with aryl chlorides. A novel air and moisture resistant Pd-PEPPSI (pyridine-enhanced precatalyst preparation, stabilization, and initiation) complex was synthesized via the reaction of benzimidazolium salt, PdCl 2 , KBr, K 2 CO 3, 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 (i pr:H 2 O/ 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. [Display omitted] [ABSTRACT FROM AUTHOR]

The palladium-based complexes bearing N-heterocyclic carbene (NHC) ligand have long attracted attention as active catalysts for many catalytic reactions. Recently, the biological activities of these complexes, which are stable to air and moisture, have also been wondered. With the aim, we report the synthesis of a series of (NHC)Pd(Br2)(L) complexes (NHC: 1,3-dibenzylbenzimidazolium, L: morpholine, triphenylphosphine, pyridine, 3-chloropyridine, and 2-aminopyridine). All complexes were characterized by NMR (1H and 13C), FTIR spectroscopic and elemental analysis techniques. In addition, the single crystal structures of the complex 3, 4, and 6 were determined through single crystal x-ray crystallographic method. Furthermore, the carbonic anhydrase I and II isoenzymes (hCAs) and acetylcholinesterase (AChE) inhibition effects of these palladium-based complexes bearing NHC ligand were investigated. They showed highly potent inhibition effect with Ki values are between 10.06 ± 1.49–68.56 ± 11.53 nM for hCA I isoenzyme, 7.74 ± 0.66 to 49.39 ± 6.50 nM for hCA II isoenzyme and 22.83 ± 3.21 to 64.09 ± 9.05 nM for AChE enzyme.

Bulky Pd−N‐heterocyclic carbene (NHC) catalysts (e. g. N‐(di‐2,6‐(3‐pentyl)phenyl), IPent) have been shown to have significantly higher reactivity in a wide variety of cross‐coupling applications (i. e. C−C, C−S, C−N) than less hindered variants (e. g. N‐(di‐2,6‐(isopropyl)phenyl), IPr). Further, chlorinating the backbone of the NHC ring sees an even greater increase in reactivity. In the cross‐coupling of (hetero)aryl electrophiles to secondary alkyl nucleophiles, making the N‐aryl groups larger reduces the amount of β‐hydride elimination leading to alkene byproducts and chlorinating the NHC core had an even greater effect, all but eliminating alkene formation. In the present study involving the cross‐coupling of primary alkyl electrophiles and nucleophiles, a sharp and surprising reversal of all of the above trends was observed. Bulkier catalysts had generally slower rate of reaction and β‐hydride elimination worsened leading to extensive amounts of alkene byproducts. [ABSTRACT FROM AUTHOR]

An in situ generated catalytic system comprised of a Pd-PEPPSI [Pyridine enhanced pre-catalyst preparation, initiation, and stabilization] complex, (NHC)PdBr2(Pyridine), and PPh3 co-ligand demonstrated excellent activity for the Sonogashira cross-coupling reactions between phenylacetylene with aryl halides in neat water under the aerobic condition in presence of CuI as co-catalyst. The catalytic system was not only compatible with electronically diverse aryl bromides/ iodides but also effective for relatively difficult substrates like heteroaryl bromides. Notably, under similar experimental conditions, the mixed PEPPSI/PPh3 system displayed superior activity over the free Pd-PEPPSI or Pd-phosphine system. This article presents an in situ Pd-PEPPSI/PPh3 catalytic system for aqueous Sonogashira reaction in presence of CuI under aerobic condition which was found to be highly efficient for coupling of anyl/heteroaryl halides with phenylacetylene to form substituted alkynes. Interestingly, it displayed superior activity over simple Pd-PEPPSI or Pd-PPh3 catalysts [ABSTRACT FROM AUTHOR]

NaBHT (sodium 2,6‐di‐tert‐butyl‐4‐methylphenolate), a strong, but hindered and lipophilic base, has been effectively paired with similarly lipophilic, high‐reactivity Pd‐NHC (N‐heterocyclic carbene) catalysts to produce an ideal combination for performing solvent‐free (melt) cross‐coupling amination. The mild nucleophilicity of NaBHT, coupled with the anti‐oxidant properties of its conjugate acid byproduct, BHT means the process seems to have no functional group incompatibilities. Highly effective coupling of base‐sensitive and redox‐active functional groups was observed in all cases with only 0.1–0.2 mol percent catalyst. Comparisons using the standard base for this reaction, KOtBu, led to poor couplings or complete degradation in most applications – only NaBHT works. [ABSTRACT FROM AUTHOR]

Pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) complexes contain two halides, an unstable pyridine derivative and a bulky N-heterocyclic carbene (NHC) ligand. In this study, a new palladium-PEPPSI complex, dichloro[1-allyl-3-(2,3,5,6-tetramethylbenzyl)benzimidazole-2-ylidene]pyridine palladium(II), was synthesized and fully characterized by elemental analysis, X-ray crystallography, FT-IR, 1H, and 13C NMR spectroscopy techniques. In addition, the molecular geometries, vibrational frequencies, and 1H and 13C NMR chemical shift values of the complex in the ground state have been calculated using the density functional theory (DFT) method with B3LLP/SDD. The frontier molecular orbitals analyses have been performed to explain the energetics and chemical reactivity of palladium-PEPPSI complex. Stability of the complex resulting from hyperconjugative interactions has been analyzed with natural bond orbital (NBO) analysis. The non-linear optical (NLO) properties have also been described calculating the polarizability and first order hyperpolarizability of the compound. [ABSTRACT FROM AUTHOR]

A set of six new catalysts possessing quinone moieties in a pyridine ligand was synthesized and fully characterized by standard analytical techniques, including X-Ray crystallography. The results obtained in Suzuki and Mizoroki-Heck cross-coupling reactions catalyzed by quinone-based compounds were comparable to these obtained in the presence of the original PEPPSI complex designed by Organ. DFT calculations allow to see the structural and electronic factors to describe their similarity. On the other hand, steric maps and NCI plots were the tools to have a more global view of the systems studied, leaving the sphere of reactivity around the metal. [ABSTRACT FROM AUTHOR]

A palladium‐catalysed Buchwald–Hartwig amination for lenalidomide‐derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl‐ and aryl‐ amines and functionalised aryl bromides. The methodology allows access to new cereblon‐based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields. [ABSTRACT FROM AUTHOR]

The role that LiBr plays in the lifetime of Pd‐NHC complexes has been investigated. A bromide ion is proposed to coordinate to Pd thereby preventing beta hydride elimination (BHE) (to form NHC‐H+) of the reductive elimination (RE) intermediate that normally completes with the desired cross‐coupling catalytic cycle. Coordinating groups, such as anilines, are able to bind suitably well to Pd to prevent this pathway from occurring, thus reducing the need for the added salt. The metal hydride formed from BHE is very unstable and RE of the hydride to the NHC ligand occurs very rapidly giving rise to the corresponding hydrido‐NHC (i.e. NHC‐H+). The use of the per deuterated dibutylzinc shows a significant deuterium isotope effect, shutting down catalyst death almost completely. The use of bis‐neopentylzinc, now possessing no hydrides, eliminates catalyst death all together leading to a very long‐lived catalytic cycle and confirming the untoward role of BHE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The impact of LiBr and ZnBr2 salts on the Negishi coupling of alkylZnBr and dialkylzinc nucleophiles with both electron‐rich and ‐poor aryl electrophiles has been examined. Focusing only on the more difficult coupling of deactivated (electron‐rich) oxidative addition partners, LiBr promotes coupling with BuZnBr, but does not have such an effect with Bu2Zn. The presence of exogenous ZnBr2 shuts down the coupling of both BuZnBr and Bu2Zn, which has been shown before with alkyl electrophiles. Strikingly, the addition of LiBr to Bu2Zn reactions containing exogenous ZnBr2 now fully restores coupling to levels seen without any salt present. This suggests that there is a very important interaction between LiBr and ZnBr2. It is proposed that Lewis acid adducts are forming between ZnBr2 and the electron‐rich Pd0 centre and the bromide from LiBr forms inorganic zincates that prevent the catalyst from binding to ZnBr2. This idea has been supported by catalyst design as chlorinating the backbone of the NHC ring of Pd‐PEPPSI‐IPent to produce Pd‐PEPPSI‐IPentCl catalyst now gives quantitative conversion, up from a ceiling of only 50 % with the former catalyst. [ABSTRACT FROM AUTHOR]

The relative rates of arylation of primary alkylamines with different Pd‐NHC catalysts have been measured, as have the relative rates of arylation of the secondary aniline product in an attempt to understand the key ligand design features necessary to have high selectivity for the monoarylated amine product. As the substituents on the N‐aryl ring of the NHC increase in size, selectivity for monoarylation increases and this is further enhanced by chlorinating the back of the NHC ring. Computations have been performed on the catalytic cycle of this transformation in order to understand the selectivity obtained with the different catalysts. [ABSTRACT FROM AUTHOR]

Benzimidazolium salts (1a and 1b) and respective palladium complexes (2a and 2b) were prepared and characterized with 1H and 13C NMR, IR, elemental analysis as well as HRMS (for 2a). All target compounds were screened as potential anticancer agents against human cell lines for assessing their cytotoxicity. Heterocyclic organic compounds (1a and 1b) showed more cytotoxic activity than their complexes (2a and 2b) in the tested two cell lines. Particularly, a benzimidazolium salt including a 4-methylbenzyl group had a high cytotoxic potency towards MDA-MB-231 and DLD-1 cell lines with IC50 values comparable to a well-known anticancer drug cisplatin, which is generally used in clinical studies. Furthermore, a compound namely 1-(2-hydroxyethyl)-3-(2,3,4,5,6-pentamethylbenzyl)-1H-benzo[d]imidazol-3-ium bromide was found to be more cytotoxic activity in MDA-MB-231 cell line compared to cisplatin with following IC50 value of 7.59 ± 0.68 μM. [ABSTRACT FROM AUTHOR]

NaBHT (sodium butylated hydroxytoluene), a hindered and soluble base for the efficient arylation of various base‐sensitive amines and (hetero)aryl halides has been found to have an unanticipated role as a hydride donor to reduce (hetero)aryl halides and allylic acetates. Mechanistic studies have uncovered that NaBHT, but not BHT, can deliver multiple hydrides through oxidation of the benzylic methyl group in NaBHT to the aldehyde. Further, performing the reduction with NaBHT‐d20 has revealed that the redox‐active benzylic position is not the only hydride donor site from NaBHT with one hydride in three coming, presumably, from the tert‐butyl groups. The reduction works well under mild conditions and, incredibly, only consumes 20 percent of the NaBHT in the process; the remaining 80 percent can be readily recovered in pure form and reused. This, combined with the low cost of the material in ton‐scale quantity, makes it practical and attractive for wider use in industry at scale. [ABSTRACT FROM AUTHOR]

In this study, we synthesized five new PEPPSI-type Pd-NHC complexes with high yields around 78–83%. The structures of all complexes were characterized by FT-IR, 1H NMR, and 13C{1H} NMR spectroscopies. Further, the structure of 2c was determined by X-ray crystallography. The single-crystal structure of 2c shows that coordination geometry around Pd is distorted square planar. The Pd-NHC complexes were efficient catalysts for the direct C5-arylation of 2-n-butylthiazole, 2-n-butylfuran, and 2-n-butylthiophene with various aryl-bromides and showed high catalytic activity for arylation reaction using only 1 mol% catalyst loading at 130 °C for 1 h. The conversions for substrates containing electron-withdrawing groups were higher than for substituents containing electron-donating groups. In order to evaluate the catalytic activity of the complexes, representative electronic and spectroscopic simulations by DFT method have been performed for 2c. NBO analysis has revealed that the strongest interaction contributing to the lowering of the molecular stabilization energy for 2c is predicted as π(C11-N27) → π*(N26-C28) with E(2) = 73.93 kcal mol−1. In addition, FMO analysis has implied that 2c is more chemically reactive because of its lower energy gap value. According to the other quantum chemical parameters, 2c is softer, better electrophile and has more charge-transfer capability than 1c. [ABSTRACT FROM AUTHOR]

The coupling of organolithium reagents, including strongly hindered examples, at cryogenic temperatures (as low as −78 °C) has been achieved with high‐reactivity Pd‐NHC catalysts. A temperature‐dependent chemoselectivity trigger has been developed for the selective coupling of aryl bromides in the presence of chlorides. Building on this, a one‐pot, sequential coupling strategy is presented for the rapid construction of advanced building blocks. Importantly, one‐shot addition of alkyllithium compounds to Pd cross‐coupling reactions has been achieved, eliminating the need for slow addition by syringe pump. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract N -Heterocyclic carbenes (NHCs) have been known to be efficient ligands for the Suzuki–Miyaura cross-coupling. In this work, four novel 2-methyl-2-propenyl substituted N- heterocyclic carbene ligands (1a-d) were synthesized and they were used to produce four novel air-stable PEPPSI-type palladium–NHC complexes (2a-d). All of the new compounds were fully characterized by elemental analysis, 1H, 13C NMR and FT-IR spectroscopies. In addition, prepared complexes (2a-d) were investigated as catalysts in the Suzuki–Miyaura coupling reaction under very mild conditions using a mixture of i-PrOH/water as a solvent and a base at the room temperature. Under optimal reaction conditions, the expected biaryl products were obtained in moderate to high yields. Graphical abstract Image 1 Highlights • N -heterocyclic carbene ligands (NHC) and their PEPPSI type Pd(II) NHC complexes have been synthesized. • All the ligands and complexes were determined by spectroscopic methods. • These [PdCl 2 (NHC) (py)] complexes have been applied for the Suzuki-Miyaura C C coupling reactions. • Good to excellent coupling products have been obtained using green solvents at room temperature in a very short time. [ABSTRACT FROM AUTHOR]

The Pd-PEPPSI complexes widely used to catalyze numerous reactions eliminate the pyridine ligand on treatment with protic acids to give binuclear complexes [Pd(NHC)X2]2 with the Pd-X-Pd (X = Cl, Br, I) bridging bonds. The reaction proceeds with high yields (78-98%) and can be regarded as a preparative approach to binuclear complexes. A prolonged heat treatment of either Pd-PEPPSI complexes or binuclear [Pd(NHC)X2]2 complexes in the presence of strong protic acids results in the Pd-NHC bond cleavage to give azolium salts (proligands) and palladium salts. [ABSTRACT FROM AUTHOR]

New benzimidazole-2-ylidene palladium(II) complexes of PEPPSI type, having pyridine as a throw-away ligand were obtained in one step from phenacyl benzimidazolium bromides and PdCl 2 . Although the presence of phenacyl groups attached to the N3 could lead in basic medium either to the N-heterocyclic carbenes or to the corresponding N -ylides, 6 new complexes were obtained without need of supplementary reactions steps or carbene transfer agents. X-ray diffraction analysis revealed that the expected chlorine atoms in the complexes were replaced by bromine atoms. [ABSTRACT FROM AUTHOR]

Benzimidazolium salts and their P yridine E nhanced P recatalyst P reparation S tabilization and I nitiation (PEPPSI) palladium N -heterocyclic carbene (Pd-NHC) based complexes have been synthesized and their structures characterized with a number of different instrumental techniques including NMR ( 1 H and 13 C), IR, EI-MS (for 2 ), X-ray (for 1 , 2 and 4 ) and elemental analysis. The cytotoxicity of all the compounds was tested using the human embryonic kidney (HEK-293T), human breast epithelial adenocarcinoma (MDA-MB-231), and human colon epithelial colorectal adenocarcinoma (DLD-1) cell lines. The benzimidazolium salts ( 2–5 ) had more cytotoxic activity against cancerous cells compared with the metal complexes ( 6–9 ), which curiously exhibited no activity against any of the cell lines. Based on the IC 50 values, compound 5 displayed the highest in vitro anticancer activity among compounds 2–9 . [ABSTRACT FROM AUTHOR]

The Pd-PEPPSI-IPentCl precatalyst (PEPPSI=pyridine-enhanced precatalyst preparation stabilisation initiation) has been demonstrated to be highly effective in the coupling of hetero(aryl)chlorides to free 2-aminopyridine substrates to produce N-(hetero)aryl-2-aminopyridine derivatives. The catalyst has proven to be competent in a number of other difficult cross-coupling reactions owing to the combination of the 3-pentyl-substituted N-aryl groups and the chlorines on the backbone of the N-heterocyclic carbene (NHC) core. This same reactivity here allows couplings to take place under very mild conditions (e.g., NaBHT (BHT=2,6-di- tert-butyl-4-methylphenol) or carbonate base) such that sensitive functional groups including esters, ketones and nitriles are tolerated. Key is that the same bulk that drives the cross-coupling also mitigates poisoning of the Pd centre with the 2-aminopyridine functionality in the starting materials and/or products, which forces the catalyst into inactive, stable resting states. [ABSTRACT FROM AUTHOR]

[Display omitted] • This work contains synthesis, characterization, crystal structure, and biological activity. • They were PEPPSI type Pd(II)NHC complexes [(NHC)Pd(II)(3-Cl- py)]. • They were synthesized by reacting benzimidazolium salts bearing a chloro/fluorobenzyl group and palladium chloride. • NMR, FTIR, and elemental analysis techniques were used. • Molecular and crystal structures of complex 1c were established by single-crystal. • They exhibited highly potent inhibition effects. • Enzymes studied were acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase I and II. 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. [ABSTRACT FROM AUTHOR]

In this paper we report the first cross-coupling reaction of Ar 3 Bi with Ar’X mediated by Pd-NHC complexes by keeping the ability of Ar 3 Bi to transfer the three aryl moieties. Investigations were carried out in order to minimize the quantity of the side product Ar-Ar coming from the conversion of Ar 3 Bi. The results showed that PEPPSI IPr was a good catalyst precursor. Efforts were focussed on the rule of each additive such as PPh 3 and the base. It was notably found that the presence of PPh 3 (ratio PEPPSI IPr/PPh 3 : 1/1) was essential to keep the process efficient. Therefore NHC-Pd-PPh 3 has been assumed as being the catalytic species. Under the optimized reaction conditions the concomitant formation of the undesired biaryl side product was restricted to its inherent formation consecutive to the reduction of the catalyst precursor to Pd(0). In a last study, the scope and the limitation of the new catalytic methodology were examined and a large range of unsymmetrical biaryl compounds Ar-Ar’ bearing various substituents from strongly electron-donating to electron-withdrawing ones have been prepared and fully characterized. [ABSTRACT FROM AUTHOR]

A robust, mild, and efficient method for the Pd-catalyzed N-heteroarylation of optically pure α-amino esters was developed. Dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene]( o-picoline)palladium(II) (Pd-PEPPSI-IPentCl- o-picoline; PEPPSI=pyridine enhanced pre-catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as the tert-butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester. Control experiments revealed that racemization is base-mediated, with no evidence of Pd-mediated β-hydride elimination when using Pd-PEPPSI-IPentCl, and that racemization occurs only after the product is formed, that is, the non-arylated starting amino ester does not deprotonate under our reaction conditions. Studies also revealed that increasing the steric bulk of the ester moiety on the amino acid (e.g., ethyl to tert-butyl) drastically slows racemization of the product. [ABSTRACT FROM AUTHOR]

Dichloro[1,3-bis(2,6-di-4-heptylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) (Pd-PEPPSI-IHeptCl), a new, very bulky yet flexible Pd-N-heterocyclic carbene (NHC) complex has been evaluated in the cross-coupling of secondary alkylzinc reactants with a wide variety of oxidative addition partners in high yields and excellent selectivity. The desired, direct reductive elimination branched products were obtained with no sign of migratory insertion across electron-rich and electron-poor aromatics and all forms of heteroaromatics (five and six membered). Impressively, there is no impact of substituents at the site of reductive elimination (i.e., ortho or even di- ortho), which has not yet been demonstrated by another catalyst system to date. [ABSTRACT FROM AUTHOR]