N-heterocyclic Carbene Palladium Complexes Research Articles

N-heterocyclic carbene complexes of palladium in oxygen atom transfer reactions involving the making and breaking of N-O bonds

Reaction of three equivalents of MesCNO (Mes=2,4,6-trimethylphenyl) with one equivalent of [Pd(IPr)(P(p-tolyl)3)] in toluene yields the solid complex [Pd(IPr)(NCMes)(κ2-O–NC-Mes(–N–C(O)Mes))]. Three major steps are proposed to be involved in the reaction based on spectroscopic studies as well as literature precedents for related cycloadditions: i. oxidation of the coordinated phosphine ligand to phosphine oxide ii. oxygen atom transfer forming a CO bond from the N–O bond of MesCNO, and iii. cycloaddition of a final MesCNO ligand to yield product.Addition of two equivalents of NO at low temperature to the in situ generated peroxide complex [Pd(IPr)2(η2-O2)] generates the N-bonded complex trans-[Pd(IPr)2(NO2)2] in keeping with a literature precedent reported for similar complexes. Insight into the energetics of this reaction are probed by DFT calculations using the truncated ligand complex [Pd(IMe)2]. The computed enthalpy of binding of two moles of NO2 to form [Pd(IMe)2(NO2)2] is −112kcal/mol indicating that its preparation from [Pd(IMe)2], N2 and 2O2 is thermodynamically favorable by −96kcal/mol. Crystal structures of [Pd(IPr)(NCMes)(κ2-O–NC-Mes(–N–C(O)Mes))] and trans-[Pd(IPr)2(NO2)2] are reported.

Palladium(II) N-heterocyclic carbene complexes as catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

Silver(I) N-heterocyclic carbene complexes were synthesized in good yields by the reactions of 1,3-dialkylperhydrobenzimidazolyum salts with silver(I) oxide and used as transmetallation reagents for the synthesis of palladium(II) N-heterocyclic carbene complexes. All of the complexes were characterized using elemental analysis, 1H NMR and 13C NMR spectroscopy. The catalytic activity of Pd(II)-NHC complexes in the direct arylation of pyrrole derivatives was investigated. These Pd(II)-NHC complexes showed the good catalytic performance for the direct arylation of pyrrole derivatives with readily available and inexpensive aryl chlorides. The arylation reactions regioselectively produced C2- or C5-arylation products in moderate to good yields by using 1mol% of the palladium complex.

Palladium–N-heterocyclic carbene complexes for the Mizoroki–Heck reaction: An appraisal

This article presents a review of the most significant developments with N-heterocyclic carbene (NHC)–palladium catalytic systems used for the Heck reaction. For more than the past two decades, a large number of new NHC–Pd complexes have been synthesized and characterized. These studies focused on NHCs as a phosphine analogue, but the current review highlights the differences with particular ligands so as to attain a suitable balance between the electronic and bulky environments around the metal. NHCs have gained wide recognition as these ligands act as excellent σ-donors that form stable metal–NHCs with strong metal–carbon bonds. For this reason, metal–NHCs are commonly used as they are highly reactive and can selectively serve as catalysts for various chemical transformations. The objective of our article is to highlight significant recent progress in NHC–Pd(II) complexes and provide an overview of their extensive interaction in the Mizoroki–Heck reaction.

Effect on orthometallation of NHC palladium complexes toward the catalytic activity studies in Suzuki coupling reaction.

Herein, we report an approach to improve catalytic activity for cross-coupling reactions. N-Heterocyclic carbene (NHC) palladium complexes bearing a nitrogen-based ligand without orthometallation complexes show remarkable activities in Suzuki coupling reaction than orthometallation. Aryl chlorides examples employed in air and ambient temperature in Suzuki coupling reaction to reach completion within few minutes.

Synthesis and catalytic applications of palladium N-heterocyclic carbene complexes as efficient pre-catalysts for Suzuki–Miyaura and Sonogashira coupling reactions

A new palladium complex series with N-heterocyclic carbene (NHC), pyridine and phosphine ligands, PdCl2(L)NHC (2a–c)(L = NHC), PdCl2(L1)NHC(3a–c)(L1 = pyridine), PdCl2(L2)NHC(4a–c)(L2 = triphenylphosphine) was synthesised and fully characterized.

Abnormal-NHC Palladium(II) Complexes: Rational Synthesis, Structural Elucidation, and Catalytic Activity

Reaction of a C2-arylated imidazolium iodide (IPrPh)I (1) (IPrPh = 1,3-bis(2,6-diisopropylphenyl)-2-phenyl-imidazolium) with PdCl2 in the presence of Ag2O affords abnormal N-heterocyclic carbene (aNHC) palladium complexes (aIPrPh)PdCl2 (2) and (aIPrPh)2PdCl2 (3) (aIPrPh = 1,3-bis(2,6-diisopropylphenyl)-2-phenyl-imidazol-4-ylidene). Treatment of 2 with a pyridine gives Pd-PEPPSI-type complexes (aIPrPh)PdCl2(L) (L = pyridine (py), 5; L = 3-chloropyridine (3Cl-py), 6). Compounds 5 and 6 are also accessible by a one-pot reaction of 1, PdCl2, and Ag2O in a pyridine solvent. While the use of a conventional base K2CO3 leads to the formation of mixed halide complexes (aIPrPh)Pd(Cl)I(L) (7, L = py; 8, L = 3Cl-py), iodide derivatives (aIPrPh)PdI2(L) (9, L = py; 10, L = 3Cl-py) can be selectively prepared with addition of an excess of KI to the reaction mixture. Albeit in a low yield, a putative transmetalation agent {(aIPrPh)2Ag}AgI2 (4) has been isolated and characterized. Compounds 2–10 are air stable crystalline...

Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression.

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N-heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N'-nBu2 NHC)](CF3 SO3 ) (Pd1 d, HC^N^N=6-phenyl-2,2'-bipyridine, N,N'-nBu2 NHC=N,N'-di-n-butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50 =0.09-0.5 μm) but is less cytotoxic toward a normal human fibroblast cell line (CCD-19Lu, IC50 =11.8 μm). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.

Synthesis of novel palladium(II) N-heterocyclic carbene complexes and their catalytic activities in the direct C5 arylation reactions

New palladium(II) N-heterocyclic carbene complexes have been easily obtained in good yields from the carbene transfer reaction of silver-NHC complexes with PdCl2(PhCN)2 and characterized by elemental analysis, 1H NMR and 13C NMR spectroscopy. These complexes were used as catalysts in the direct C5 arylation of 2-n-butylfuran, 2-n-butylthiophene and 2-n-propylthiazole with various aryl bromides at 130°C in N,N-dimethylacetamide (DMAc) for 1h. The arylation reactions were regioselective, and in all cases, only the C5-arylated products were formed. The corresponding arylation products were obtained in moderate to good yields by using 0.5mol% of palladium-NHC complexes.

Synthesis and crystal structures of palladium(II) complexes of bis-(N-heterocyclic carbenes) on a calix[4]arene platform

A series of calix[4]arene supported N-heterocyclic carbene palladium complexes were successfully prepared and characterised. Their X-ray crystal structures were obtained and are discussed. Notably, the dimeric compound b[5-(3-N-4,5-diphenylimidazol-2-yliden-1-yl)-25,26,27,28-tetrapropyloxy calix[4]arene] palladium(II) dibromide (cone) showed pseudo-polymorphism.

Synthesis of silver(I) and palladium(II) N-heterocyclic carbene complexes and their use as catalysts for the direct C5 arylation of heteroaromatic compounds

Silver(I) N-heterocyclic carbene complexes were synthesized in good yields by the reactions of 1,3-dialkylperhydrobenzimidazolium salts with silver(I) oxide in dichloromethane. The silver complexes were used as carbene-transfer agents to synthesize palladium(II) N-heterocyclic carbene complexes. All of the complexes were characterized by physicochemical and spectroscopic methods. The new palladium complexes were tested as catalysts in the direct C5 arylation of 2-n-butylfuran, 2-n-butylthiophene and 2-n-propylthiazole with aryl bromides at 130 °C in N,N-dimethylacetamide. The arylation reactions proceeded selectively at the C5 position of the heteroaromatic compounds, and the corresponding coupling products were obtained in moderate to good yields by using 0.5 mol% of the palladium complex.

Catalytic activity of chelating N-heterocyclic carbene palladium complexes towards selective phosphorylation of coumarins

The catalytic activity of a series of heteroaryl coordinated chelating N-heterocyclic carbene (NHC) palladium complexes bearing different N-substituents, NHC backbones and chelating rings towards the phosphorylation of coumarins, and the relationship between the activity and the structure are presented. The results showed that the chelating NHC palladium complex Ia–b bearing the most σ-donating backbone and a more rigid five-membered chelating ring showed the highest efficiency. Using AgNO3 as oxidant, a wide range of coumarins reacted with different dialkyl phosphite or diphenylphosphine oxide smoothly in CH3CN, producing the target product in moderate to high yields.

In vitro cytotoxic activities of new silver and PEPPSI palladium N-heterocyclic carbene complexes derived from benzimidazolium salts

New benzimidazolium salts (2, 3) and their silver (4, 5) and palladium (6, 7) N-heterocyclic carbene (Ag- and Pd-NHC) complexes were designed, synthesized and structurally characterized by NMR (1H and 13C), IR, HRMS and UV–Vis spectroscopic methods. All the synthesized compounds were tested in human colon cancer (DLD-1), breast cancer (MDA-MB-231) and embryonic kidney (HEK 293T) (non-cancerous) cell lines for in vitro cytotoxicity. Compound 4 specifically showed low IC50 values for these cell lines (IC50 values 12.41±2.89, 11.98±2.52 and 4.21±1.74μmol/L in DLD-1, MDA-MB-231 and HEK 293T cell lines, respectively). The Pd-NHC complexes (6, 7) did not exhibit cytotoxic activity (IC50 values >200 in DLD-1, MDA-MB-231, HEK 293T cell lines). Therefore, Ag-NHC complexes can be further investigated as potential anticancer agents.

Palladium(II) Complexes with Anionic N-Heterocyclic Carbene–Borate Ligands as Catalysts for the Amination of Aryl Halides

A series of (allyl)palladium(II) complexes of anionic N-heterocyclic carbenes that contain a weakly coordinating borate moiety (WCA-NHC) were prepared by deprotonation of the carbene IPr with n-butyllithium in the 4-position, which was followed by addition of B(C6F5)3 and reaction of the resulting lithium carbene–borate with [(η3-allyl)Pd(μ-Cl)]2 (allyl = 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 1-phenyl-2-propenyl). In polar solvents such as tetrahydrofuran, chloropalladate complexes of the type [Li(THF)3][(WCA-NHC)PdCl(η3-allyl)] were formed, whereas the reactions in toluene afforded neutral complexes of the type [(WCA-NHC)Pd(η3-allyl)], which exhibit an intramolecular interaction with the N-aryl groups of the carbene ligands. The allyl-palladium complexes were employed as catalysts for the Buchwald–Hartwig amination of various aryl halides with morpholine.

Palladium complexes of anionic N-heterocyclic carbenes derived from sydnones in catalysis

Abstract The anion of N-phenylsydnone, which can be generated on treatment of N-phenylsydnone with cyanomethyllithium without decomposition, can be represented as tripolar zwitterionic and as anionic N-heterocyclic carbene resonance forms. Its palladium complex was prepared from 4-bromo-3-phenylsydnone and tetrakis(triphenylphosphine)palladium and proved to be active as catalyst in Suzuki-Miyaura reactions. Thus, 2,5-dibromo-3,4-dinitrothiophene was effectively converted into 2,5-diaryl-3,4-dinitrothiophenes with 1-naphthyl, (4-trifluoromethoxy)phenyl, [4-(methylsulfanyl)phenyl], and biphenyl-4-yl boronic acid. 3-(Phenanthren-9-yl)quinoline was prepared by Suzuki-Miyaura reaction starting from 3-bromoquinoline. 1-Chloro-2,4-dinitrobenzene cross-coupled with phenyl boronic acid, 1-naphthyl boronic acid, 9-phenanthryl boronic acid. 4-Bromobenzylic alcohol gave (4-isopropylphenyl)methanol on sydnone-palladium complex-catalyzed reaction with isopropyl boronic acid.

Supporting ligand-assisted N-heterocyclic carbene palladium complexes: characterization, computation, and catalytic activity in Suzuki–Miyaura cross coupling between aryl and heteroaromatic chlorides and various boronic acids

A new series of imine–Pd–(N-heterocyclic carbene) complexes have been developed as efficient catalysts for Pd-catalyzed Suzuki–Miyaura coupling reaction. Based on the performance of supporting ligands, correlation of structure and catalytic activity has been demonstrated via experimental and computational modeling. A broad reaction scope of aryl and heteroaromatic chlorides could proceed at extremely low catalyst loading (minimum 0.005mol%).

Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined Palladium N-Heterocyclic Carbene Complexes.

Well-defined palladium N-heterocyclic carbene (NHC) complexes were employed in the one-pot tandem Heck alkynylation/cyclization sequence for preparing biologically relevant benzofuran compounds under copper-free conditions in a time-efficient step-reduced fashion. In particular, a series of binuclear palladium complexes, 1b-1e and 2b-2e, of the alkyl-bridged NHC ligands, namely, {1,1'-di-R1-4,4'-R2-di-1,2,4-triazoline-5,5'-diylid-2-ene] (R1 = i-Pr; R2 = -(CH2)2-, -(CH2)3-), and their mononuclear analogues, trans-(NHC)PdBr2(pyridine) (3b) and cis-(NHC)PdBr2(PPh3) (3c), successfully catalyzed the one-pot tandem Heck alkynylation/cyclization reaction of 2-iodophenol with a variety of terminal alkyne substrates, yielding 2-substituted benzofuran derivatives. The mononuclear complexes 3b and 3c were nearly half as active as the representative dinuclear analogue 1c under analogous reaction conditions, thereby implying that, at the same mole percent of the palladium loading, the monometallic 3b and 3c and the bimetallic 1c complexes were equally effective as catalysts. The two sites of the bimetallic complex 1c performed as two separate independent catalytic sites, displaying no cooperativity effect in the catalysis. Finally, the practical utility of the aforementioned catalysts was demonstrated for a representative catalyst 1c through the convenient synthesis of a key intermediate, 3-[2-(benzo[d][1,3]dioxol-5-yl)-7-methoxybenzofuran-5-yl]propan-1-ol, in a total-synthesis protocol of the natural product Egonol.

Synthesis of conjugated Mn porphyrin polymers with p-phenylenediamine building blocks and efficient aerobic catalytic oxidation of alcohols

A series of conjugated metalloporphyrin polymers (MnP-AMPs) were synthesized based on Buchwald-Hartwig aromatic amination with p-phenylenediamine and manganese tetraphenylporphyrin as building blocks, and N-heterocyclic carbene-palladium complex as catalyst. Brunauer–Emmett–Teller surface area analysis, scanning electron microscopy and transmission electron microscopy showed that MnP-AMPs had large surface areas and uniform pore sizes. The stable porous and superreticular conjugated structure of MnP-AMP further activated manganese ions in the porphin ring compared with those in the original monomanganeseporphyrin. Moreover, introducing CN bonds in MnP-AMP increased its polarity and affinity to alcohols, so MnP-AMP exhibited high catalytic activity when applied to aerobic oxidation of alcohols. For the catalysis of selective oxidation of benzyl alcohol to benzaldehyde with air, the conversion and aldehyde selectivity both reached up to 100% under mild condition in acetonitrile at 40°C. MnP-AMP also remained stable in oxidation reaction system and still had high catalytic activity after several recycles.

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd-NHC complexes: synthesis, characterization and catalytic activity in carbon-carbon bond-forming reactions.

A series of novel benzimidazolium salts (1–4) and their pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)] (5–8), where NHC = 1-(N-methylphthalimide)-3-alkylbenzimidazolin-2-ylidene and Py = 3-chloropyridine, were synthesized and characterized by means of 1H and 13C{1H} NMR, UV–vis (for 5–8), ESI-FTICR-MS (for 2, 4, 6–8) and FTIR spectroscopic methods and elemental analysis. The synthesized compounds were tested in Suzuki–Miyaura cross-coupling (for 1–8) and arylation (for 5–8) reactions. As catalysts, they demonstrated a highly efficient route for the formation of asymmetric biaryl compounds even though they were used in very low loading. For example, all compounds displayed good catalytic activity for the C–C bond formation of 4-tert-butylphenylboronic acid with 4-chlorotoluene.

Intermolecular Hydroamination of Styrene Catalyzed by Palladium(II) N-Heterocyclic Carbene Complexes in Ionic Liquid

Intermolecular Hydroamination of Styrene Catalyzed by Palladium(II) N-Heterocyclic Carbene Complexes in Ionic Liquid

Amino acid-derived N-heterocyclic carbene palladium complexes for aqueous phase Suzuki–Miyaura couplings

Five palladium complexes featuring N-heterocyclic carbene ligands derived from sustainable precursors have been synthesized and applied in aqueous Suzuki–Miyaura couplings.