Heterocyclic Carbene Complexes Research Articles

Mononuclear Cu Complexes Based on Nitrogen Heterocyclic Carbene: A Comprehensive Review.

During the last decade, organometallic, coordination, and catalytic chemistry of the three-dimensional metals such as copper (Cu) has been greatly affected by the emergence of nitrogen heterocyclic carbene (NHC) complexes. The NHCs, and in particular the mononuclear CuI-based ones, have been proven vastly useful in several applications such as in biosynthesis, catalysis, photochemistry, etc. This review tries to thoroughly describe a series of mononuclear CuI NHC complexes and their subcategories such as heteroleptics, and bidentate and tridentate heteroatom complexes, and give some detailed insights on their development, emergence, and applications. A brief outlook is also disclosed to enable other researchers to further develop a platform for future advances and studies in the field of CuI-based NHCs.

Nickel(II) Phosphane‐ and N‐heterocyclic Carbene Complexes with Tridentate, Dianionic [S,N,O]2– Ligands

Square‐planar dinuclear nickel(II) complexes containing [S,N,O]2– ligands formed by condensation of acetyl acetone or benzoyl acetone with cysteamine were prepared. These dimeric nickel(II) compounds undergo bridge‐cleavage reactions with the cage phosphine PTA (PTA = 1,3,5‐triaza‐7‐phosphaadamantane) or in situ generated N‐heterocyclic carbenes. The resulting diamagnetic, square planar NiII complexes were characterized by spectroscopic methods and X‐ray diffraction.

A four-coordinate Cu(I)–N-heterocyclic carbene complex: Synthesis, structure, properties, and application in amination for the synthesis of 1-(2-N-heteroaryl)-1H-pyrazoles

A new luminescent, cationic, heteroleptic, four-coordinate Cu(I)– N-heterocyclic carbene complex [Cu(Br-Pyim)(POP)](PF6) is successfully prepared and characterized, where Br-Pyim and POP are 1-(6-bromopyridin-2-yl)imidazole-3-benzyl-2-ylidene and bis[2-(diphenylphosphino)phenyl]ether, respectively. Its detailed structure is determined by single-crystal X-ray analysis. It exists as a crystalline powder at room temperature and exhibits bright yellow-green emission. The use of the Cu(I)– N-heterocyclic carbene complex as a catalyst for amination reactions is also investigated and is found to be very efficient for the amination of 2- N-heteroaryl chlorides with pyrazoles, giving the desired substituted 1-(2- N-heteroaryl)-1 H-pyrazoles in good yields.

Coumarin incorporated 1,2,4–triazole derived silver(I) N–heterocyclic carbene complexes as efficient antioxidant and antihaemolytic agents

Three series of structurally and electronically varied silver complexes of coumarin and allyl substituted N–heterocyclic carbene (NHC) ligands derived from 1,2,4–triazole core have been prepared and characterized. The ionic 1,2,4–triazolium salts have been prepared by successive N–alkylation method using allyl bromide and appropriately substituted 4–bromomethylcoumarin derivatives. Further, in–situ deprotonation method for triazolium salts was followed with different silver sources (silver oxide and silver acetate) and reaction conditions to obtain structurally diverse silver NHC coordination architectures. Furthermore, the structure of 4–bromomethyl–6–chlorocoumarin, a triazolium salt and two silver complexes has been established by single crystal X–ray diffraction technique. The silver NHC complexes displayed a linear coordination geometry with monoclinic crystal system. Supramolecular assembly of the salt and the complexes evidenced moderate π − π stacking interactions between adjacent coumarin rings. Since silver(I) NHC complexes are well known for medicinal properties, present complexes have been studied for their potent antioxidant and antihaemolytic abilities. Bis–NHC coordinated silver hexafluorophosphate complexes displayed DPPH radical scavenging activity with an IC50 value in the range 61 ± 14 to 131 ± 7 μM, while others displayed moderate to poor activity. Similarly, antihaemolytic activity has been carried out at 100 μM concentration, and the complexes exhibited lysis of red blood cells as low as 2.32 ± 0.05%.

Stereoselective Olefin Ring‐Opening Cross Metathesis Catalyzed by Molybdenum Imido Alkylidene N‐Heterocyclic Carbene Complexes

AbstractThe influence of the structure of cationic molybdenum imido alkylidene N‐heterocyclic carbene (NHC) catalysts, i. e. of [Mo(N‐2‐tert‐butyl‐C6H4) (CHCMe2Ph)(NHC)X+ B(ArF)4−] (NHC=1,3‐di(2‐Pr)imidazol‐2‐ylidene (iPr), 1,3‐dimesitylimidazol‐2‐ylidene (IMes); X=pyrrolide, OCH(CF3)2, B(ArF)4−=tetrakis(3,5‐bis(trifluoromethyl)phenyl)borate) and of [Mo(N‐3,5‐Me2‐C6H3)(CHCMe2Ph)(NHC)(CH3CN)X+ B(ArF)4−] (NHC=1,3‐dimesitylimidazol‐2‐ylidene, 1,3‐dimesitylimidazolin‐2‐ylidene (IMesH2); X=CF3SO3, OCPh(CF3)2) on E/Z‐selectivity in the ring‐opening cross‐metathesis (ROCM) of endo, endo‐2,3‐dicarbomethoxynorborn‐5‐ene (endo, endo‐DCMNBE), exo, exo‐2,3‐dicarbomethoxynorborn‐5‐ene (exo, exo‐DCMNBE), endo, exo‐2,3‐dicarbomethoxynorborn‐5‐ene ((+) DCMNBE) and 2,3‐exo,exo‐bis(acetoxymethyl)‐7‐oxabicyclo[2.2.l]hept‐5‐ene (7‐oxa‐NBE) with 1‐pentene, styrene, allyltrimethylsilane, allyl benzyl ether, allyl phenyl ether and allyl ethyl ether has been studied. With the exception of the ROCM reaction of endo, endo‐DCMNBE with styrene, all other ROCM reactions of endo, endo‐DCMNBE proceeded under thermodynamic control without any post‐metathesis isomerization reactions with full retention of the configuration of the newly formed 1,2‐disubstituted double bond as confirmed by kinetic studies. Similar accounts for selected homometathesis reactions. Catalyst structure‐selectivity correlations based on the buried volume, Vbur, of the N‐imido ligand are presented.magnified image

Direct C—H Bond Activation of Benzoxazole and Benzothiazole with Aryl Bromides Catalyzed by Palladium(II)‐N‐heterocyclic Carbene Complexes

Direct C—H Bond Activation of Benzoxazole and Benzothiazole with Aryl Bromides Catalyzed by Palladium(II)‐<i>N</i>‐heterocyclic Carbene Complexes

Mechanism of Olefin Metathesis with Neutral and Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes.

A series of neutral molybdenum imido alkylidene N-heterocyclic carbene (NHC) bistriflate and monotriflate monoalkoxide complexes as well as cationic molybdenum imido alkylidene triflate complexes have been subjected to NMR spectroscopic, X-ray crystallographic, and reaction kinetic measurements in order to gain a comprehensive understanding about the underlying mechanism in olefin metathesis of this new type of catalysts. On the basis of experimental evidence and on DFT calculations (BP86/def2-TZVP/D3/cosmo) for the entire mechanism, olefinic substrates coordinate trans to the NHC of neutral 16-electron complexes via an associative mechanism, followed by dissociation of an anionic ligand (e.g., triflate) and formation of an intermediary molybdacyclobutane trans to the NHC. Formation of a cationic complex is crucial in order to become olefin metathesis active. Variations in the NHC, the imido, the alkoxide, and the noncoordinating anion revealed their influence on reactivity. The reaction of neutral 16-electron complexes with 2-methoxystyrene is faster for catalysts bearing one triflate and one fluorinated alkoxide than for catalysts bearing two triflate ligands. This is also reflected by the Gibbs free energy values for the transition states, ΔG‡303, which are significantly lower for catalysts bearing only one triflate than for the corresponding bistriflate complexes. Reaction of a solvent-stabilized cationic molybdenum imido alkylidene N-heterocyclic carbene (NHC) monotriflate complex with 2-methoxystyrene proceeded via an associative mechanism too. Reaction rates of both solvent-free and solvent-stabilized cationic Mo imido alkylidene NHC catalysts with 2-methoxystyrene are controlled by the cross-metathesis step but not by adduct formation.

Formation of anionic NHC complexes through the reaction of benzimidazoles with mercury chloride. Subsequent protonation and transmetallation reactions

Anionic nitrogen heterocyclic carbene complexes of C,N-bound mercuramacrocycles {Hg4Cl4(R-Bim)4} (BimH = benzimidazole; R = Ph, Py) were prepared either from the simple reaction of N-substituted benzimidazoles with HgCl2 or from the reaction of N-substituted benzimidazoles with Hg(OAc)2 and NaCl. The former reaction is unique as no additional base is required, although in low reaction yield. Under similar reaction conditions, only N-bound benzimidazole complexes were obtained when HgBr2 or HgI2 instead of HgCl2 was employed. The different reactivity could be due to the hard-soft acid-base property of mercury(II) and halides, that facilitates the cleavage of Hg-Cl bond and promotes the C-metallation of HgCl2 and benzimidazole. Upon protonation of {Hg4Cl4(R-Bim)4} with HBF4⋅OEt2, NH,NR-NHC complexes of [HgCl(R-Bim-H)][BF4] (R = Ph, Py) were obtained. Preliminary study on the transmetallation reaction of {Hg4Cl4(Ph-Bim)4} with PdCl2(CH3CN)2 and LiCl did provide a C,N-bound NHC palladium complex.

Synthesis of polymer-linked copper(i) bis(N-heterocyclic carbene) complexes of linear and chain extended architecture

Novel PS-based mechanophores of linear and chain-extended architecture are synthesized obtaining bis(NHC) complexes with more than one Cu(i) center per chain and molecular weights of up to 50 000 g mol−1.

From Catalysis to Cancer: Toward Structure-Activity Relationships for Benzimidazol-2-ylidene-Derived N-Heterocyclic-Carbene Complexes as Anticancer Agents.

The promise of the metal(arene) structure as an anticancer pharmacophore has prompted intensive exploration of this chemical space. While N-heterocyclic carbene (NHC) ligands are widely used in catalysis, they have only recently been considered in metal complexes for medicinal applications. Surprisingly, a comparatively small number of studies have been reported in which the NHC ligand was coordinated to the RuII(arene) pharmacophore and even less with an OsII(arene) pharmacophore. Here, we present a systematic study in which we compared symmetrically substituted methyl and benzyl derivatives with the nonsymmetric methyl/benzyl analogues. Through variation of the metal center and the halido ligands, an in-depth study was conducted on ligand exchange properties of these complexes and their biomolecule binding, noting in particular the stability of the M-CNHC bond. In addition, we demonstrated the ability of the complexes to inhibit the selenoenzyme thioredoxin reductase (TrxR), suggested as an important target for anticancer metal-NHC complexes, and their cytotoxicity in human tumor cells. It was found that the most potent TrxR inhibitor diiodido(1,3-dibenzylbenzimidazol-2-ylidene)(η6-p-cymene)ruthenium(II) 1bI was also the most cytotoxic compound of the series, with the antiproliferative effects in general in the low to middle micromolar range. However, since there was no clear correlation between TrxR inhibition and antiproliferative potency across the compounds, TrxR inhibition is unlikely to be the main mode of action for the compound type and other target interactions must be considered in future.

Distinct Catalytic Performance of Cobalt(I)–N-Heterocyclic Carbene Complexes in Promoting the Reaction of Alkene with Diphenylsilane: Selective 2,1-Hydrosilylation, 1,2-Hydrosilylation, and Hydrogenation of Alkene

Selectivity control on the reaction of alkene with hydrosilane is a challenging task in the development of non-precious-metal-based hydrosilylation catalysts. While the traditional way of selectivity control relies on the use of different ligand type and/or different metals, we report herein that cobalt(I) complexes bearing different N-heterocyclic carbene ligands (NHCs) exhibit distinct selectivity in catalyzing the reaction of alkene with Ph2SiH2. [(IAd)(PPh3)CoCl] (IAd = 1,3-diadamantylimidazol-2-ylidene) is an efficient catalyst for anti-Markovnikov hydrosilylation of monosubstituted alkenes. [(IMes)2CoCl] (IMes = 1,3-dimesitylimidazol-2-ylidene) shows Markovnikov-addition selectivity in promoting the hydrosilylation of aryl-substituted alkenes. [(IMe2Me2)4Co][BPh4] (IMe2Me2 = 1,3-dimethyl-4,5-dimethylimidazol-2-ylidene) can catalyze hydrogenation of alkenes with Ph2SiH2 as the terminal hydrogen source. Mechanistic studies in combination with the knowledge on the steric nature of cobalt–NHC species su...

On the Mechanism of Gold/NHC Compounds Binding to DNA G‐Quadruplexes: Combined Metadynamics and Biophysical Methods

AbstractThe binding modes and free‐energy landscape of two AuI/N‐heterocyclic carbene complexes interacting with G‐quadruplexes, namely a human telomeric (hTelo) and a promoter sequence (C‐KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the absolute gold complex/DNA binding free energy. This advanced in silico approach is valuable to achieve rational drug design of selective G4 binders.

Direct C—H Bond Activation of Benzoxazole and Benzothiazole with Aryl Bromides Catalyzed by Palladium(II)‐N‐heterocyclic Carbene Complexes

AbstractHerein, we report that a series of novel palladium(II)‐NHC complexes (NHC=N‐heterocyclic carbene) were synthesized. The structures of all novel complexes were characterized by 1H NMR, 13C NMR, FT‐IR spectroscopy and elemental analysis techniques. These palladium(II)‐NHC complexes were tested as efficient catalysts in the direct C—H bond activation of benzoxazole and benzothiazole with aryl bromides in the presence of 1 mol% catalyst loading at 150 °C for 4 h. Under the given conditions, various aryl bromides were successfully applied as the arylating reagents to achieve the 2‐arylbenzoxazoles and 2‐arylbenzothiazoles in acceptable to high yields.

Palladium(II)‐N‐Heterocyclic Carbene Complexes: Efficient Catalysts for the Direct C‐H Bond Arylation of Furans with Aryl Halides

This paper contains the synthesis and characterization of the seven new benzimidazolium salts and their corresponding new palladium(II)‐NHC complexes with the general formula [PdX2(NHC)2], (NHC = N‐heterocyclic carbene, X = Cl or Br), and also their catalytic activity in direct C‐H bond arylation of 2‐substituted furan derivatives with aryl bromides and aryl chlorides. Under the optimal conditions, these palladium(II)‐NHC complexes showed the good catalytic performance for the direct C‐H bond arylation of 2‐substituted furans with (hetero)aryl bromides, and with readily available and inexpensive aryl chlorides. The C‐H bond arylation regioselectively produced C5‐arylated furans by using 1 mol% of the palladium(II)‐NHC catalysts in moderate to high yields.

Michael addition of cyclic β-oxo ester and α-methyl cyano ester substrates with activated olefins by iron complexes of benzimidazole derived N-heterocyclic carbene ligands

Michael addition reactions of cyclic β-oxo ester and α-methyl cyano ester substrates with acceptor activated olefins were catalyzed by iron N−heterocyclic carbene (NHC) complexes of the type, {Cp[1-benzyl-3-alkyl-benzimidazol-2-ylidene]Fe(CO)2}I, where [alkyl = i-Pr (1) and Et (2)] in the presence of l-proline as chiral auxiliary under ambient conditions. In case of the cyclic β-oxo ester substrates good yields of up to 68% and enantioselectivities of up to 18% were observed while for the α-methyl cyano ester substrates similar yields of up to 82% and enantioselectivities of up to 8% were observed. Notably, for the cyclic β-oxo ester substrates, the five membered ethyl-2-oxocyclopentane-1-carboxylate gave superior yields and enantioselectivities over the six membered ethyl-2-oxocyclohexane-1-carboxylate. In case of α-methyl cyano ester substrates, methyl vinyl ketone gave higher yields as compared to the other acceptor activated olefins namely, ethyl vinyl ketone and acrylonitrile. Based on the mass spectrometry studies, that detected the presence of l-proline adduct species (1–2)A, l-proline and substrate adduct species (1–2)B and l-proline and product adduct species (1–2)C in the catalysis reaction mixture, a mechanistic cycle has been proposed for the Fe−NHC mediated Michael addition reaction.

Ether and coumarin–functionalized (benz)imidazolium salts and their silver(I)–N–heterocyclic carbene complexes: Synthesis, characterization, crystal structures and antimicrobial studies

To explore the impact of different coumarin substituted N–heterocyclic carbene (NHC) ligand backbones on the biological applications of corresponding silver(I) complexes, a series of structurally related ether–functionalized imidazolium (3–5) and benzimidazolium (6–8) hexafluorophosphate salts bearing 6–methylcoumarin, 6–chlorocoumarin and 5,6–benzannulated coumarin substituents, have been reported. These salts have been employed to react with silver(I) oxide at mild reaction conditions to obtain corresponding ionic, bis–NHC coordinated silver(I) hexafluorophosphate complexes (9–14) in excellent yields following in situ deprotonation method. Further, the bromide counterparts of the salts have been treated with silver(I) oxide in dichloromethane to afford neutral mono–NHC coordinated bromido silver(I) complexes (15–20). Both, azolium salts and their silver(I)–NHC complexes, have been thoroughly characterized by 1H and 13C NMR, ATR–IR and elemental analyses. The structure of a benzannulated coumarin substituted imidazolium hexafluorophosphate salt 5 and a silver complex 12 of benzimidazole–based NHC bearing methylcoumarin substituent have been studied through single crystal X–ray diffraction technique. In the case of complex 12, the metal center lies at the inversion center adopting linear coordination geometry with anti– arrangement of the NHC ligands. Feeble π–π stacking interactions between adjacent coumarin rings have been evident in the extended complex structure along with the hydrogen bonding interactions. In the preliminary antibacterial evaluations, silver complexes displayed promising activity with the MIC values in the range 8–64 μg/mL against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi, while azolium salts displayed almost no activity.

Tailored molybdenum imido alkylidene N‐heterocyclic carbene complexes as latent catalysts for the polymerization of dicyclopentadiene

ABSTRACTThree novel molybdenum imido alkylidene N‐heterocyclic carbene (NHC) pre‐catalysts, that is, Mo(N‐t‐Bu)(1‐(2,6‐diisopropylphenyl)‐3‐isopropyl‐4‐phenyl‐1H‐1,2,3‐triazol‐5‐ylidene)(CHCMe2Ph)(OTf)2 (I1, OTf = CF3SO3), Mo(N‐t‐Bu)(1‐(2,6‐diisopropylphenyl)‐3‐isopropyl‐4‐phenyl‐1H‐1,2,3‐triazol‐5‐ylidene)(CHCMe2Ph)(OTf)(t‐BuO) (I2) and Mo(N‐2,6‐Me2‐C6H3)(1,3,4‐triphenyl‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ylidene)(CHCMe2Ph)(OTf)2 (I3) are presented. Compared to complexes based on imidazol‐2‐ylidenes or imidazolin‐2‐ylidenes, (1‐(2,6‐diisopropylphenyl)‐3‐isopropyl‐4‐phenyl‐1H‐1,2,3‐triazol‐5‐ylidene) used in precatalysts I1 and I2 exerts a comparably strong trans effect to the triflate groups trans to the NHC, while (1,3,4‐triphenyl‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ylidene) used in I3 has a weaker trans effect on the triflate. In combination with a suitable second anionic ligand at molybdenum, that is, OTf, t‐BuO, compounds I1–I3 require higher temperatures to become active and can thus be used as truly room temperature latent pre‐catalysts, even for a highly reactive monomer such as dicyclopentadiene (DCPD). When used as latent precatalysts, I1–I3 offer access to poly‐DCPD with different degrees of cross‐linking and glass‐transition temperatures (Tg). © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3028–3033

Silver–N‐Heterocyclic Carbene Complexes: Synthesis, Characterization, and Antimicrobial Properties

Six new silver complexes containing symmetrical N‐heterocyclic carbene (NHC) ligands were synthesized by the reaction of azolium salts with Ag2O in CH2Cl2 . These complexes were tested against Gram‐negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa), Gram‐positive bacterial strains (Enterococcus faecalis and Staphylococcus aureus), and fungal strains (Candida albicans and Candida tropicalis), and all tested complexes showed good activity against the different microorganisms.

Substituent and Solvent Effects on the Stability of N-Heterocyclic Carbene Complexes with CO2.

Carbon dioxide forms covalent complexes with N-heterocyclic carbenes. These complexes are of interest in catalysis as well as for their potential use in various carbon capture and storage strategies. A previous report showed that the stability of one such complex, N,N-dimethylimidazolium 2-carboxylate, was remarkably sensitive to solvent polarity. Polar environments lead to a kinetically stronger, shorter, and more polar bond between the carbene and CO2. The current study shows that this solvent effect is general across a wide range of NHC complexes with CO2. Computational modeling at the DFT level shows that the lability of these bonds can be controlled by steric pressure due to substituents on the heteroatoms flanking the carbene center, as well as inductive electronic effects from substituents on the C4 and C5 positions. Moreover, a strong correlation between the gas-phase NHC-CO2 bond distance and the Gibbs free energy barrier for decarboxylation is demonstrated.

Synthesis, characterization, crystal structure and in vitro anticancer potentials of mono and bimetallic palladium(II)–N–heterocyclic carbene complexes

N–heterocyclic carbene (NHC) complexes of palladium(II) are generally active as catalysts toward various coupling reactions, while their pharmacological efficiencies are seldom explored. A new series of palladium(II) complexes of both, functionalized and non–functionalized NHCs that were active against the human colon cancer (HCT116) cells are reported. Complexes were prepared by the technique of transmetallation using palladium source and in situ prepared silver(I)–NHC complexes in acetonitrile, and all complexes are characterized using spectroscopic and analytical tools. Additionally, the structure of palladium complex 9 was elucidated using single crystal X–ray diffraction method. In vitro anticancer studies revealed that the palladium complexes, 9 and 10, having xylyl–spacers significantly inhibited the HCT116 cell growth, exhibiting IC50 values in low micromolar range in MTT assay.