Stable N-heterocyclic Carbene Research Articles

N-heterocyclic carbenes – The design concept for densely packed and thermally ultra-stable aromatic self-assembled monolayers

Self-assembled monolayers (SAMs) of N-heterocyclic carbenes (NHCs) on metal substrates are currently one of the most promising systems in context of molecular-scale engineering of surfaces and interfaces, crucial for numerous applications. Interest in NHC SAMs is mainly driven by their assumingly higher thermal stability compared to thiolate SAMs most broadly used at the moment. Most of the NHC SAMs utilize imidazolium as an anchoring group for linking molecules to the metal substrate via carbene C atom. It is well established in the literature that standing up and stable NHC SAMs are built only when using bulky side groups attached to nitrogen heteroatoms in imidazolium moiety, which, however, leads to monolayers exhibiting much lower packing density compared to thiolate SAMs. Here, by combined X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and temperature-programmed secondary ion mass spectrometry analysis, we demonstrate that using NHCs with small methyl side groups in combination with simple, solution-based preparation leads to the formation of aromatic monolayers exhibiting at least doubled surface density, upright molecular orientation, and ultra-high thermal stability compared to the NHC SAMs reported before. These parameters are crucial for most applications, including, in particular, molecular and organic electronics, where aromatic SAMs serve either as a passive element for electrode engineering or as an active part of organic field effect transistors and novel molecular electronics devices.

Air stable N-heterocyclic carbene silver complexes: synthesis, characterization, and antibacterial activity

A new benzimidazolium salt containing a 2,5-dimethylbenzyl substituent and six N-heterocyclic carbene (NHC) silver complexes were prepared. The complexes were characterized by NMR, FTIR, and LC-MS spectroscopic methods and elemental analyses. They are stable in solution for a week. The antibacterial properties of the Ag(I) complexes against two Gram-positive and two Gram-negative bacteria were investigated. Inhibition zone and minimum inhibitory concentration (MIC) data establish that these NHC-Ag(I) complexes possess antibacterial activities; 2b showed the highest antibacterial activity overall against Gram-positive and Gram-negative bacteria.

Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes.

A set of 16 chiral ruthenium complexes containing atropisomerically stable N-Heterocyclic Carbene (NHC) ligands was synthesized from prochiral NHC precursors. After a rapid screening in asymmetric ring-opening-cross metathesis (AROCM), the most effective chiral atrop BIAN-NHC Ru-catalyst (up to 97 : 3 er) was then converted to a Z-selective catechodithiolate complex. The latter proved to be highly efficient in Z-selective AROCM of exo-norbornenes affording valuable trans-cyclopentanes with excellent Z-selectivity (>98 %) and high enantioselectivity (up to 96.5 : 3.5 er).

NHC-gold(I)-alkyne complexes induced hepatocellular carcinoma cell death through bioorthogonal activation by palladium complex in living system

Bioorthogonal reactions can take place in biological environments without interfering with biochemical processes. In this study, Pd(PPh3)2Cl2 was used as a bioorthogonal catalyst to in situ transform the stable N-heterocyclic carbene (NHC)-gold(I)-alkyne complex 5 to its active species which can effectively inhibit thioredoxin reductase (TrxR) and exhibit significant anticancer bioactivity in hepatocellular carcinoma (HCC).

Mimicking the C2 molecule: M2B2 and M3B2+ clusters (M = Li, Na) and the reactivity of the N-heterocyclic carbene bound Li2B2 complex.

C2 has attracted considerable attention from the scientific community for its debatable bonding situation. Herein, we show that the global minima of M2B2 and M3B2+ (M = Li, Na) possess similar covalent bonding patterns to C2. Because of strong charge transfer from M2/M3 to B2 dimer, they can be better described as [M2]2+[B2]2- and [M3]3+[B2]2- salt complexes with the B22- core surrounded perpendicularly by two and three M+ atoms, respectively. The energy decomposition analyses in combination with the natural orbital for chemical valence theory give four bonding components in C2, M2B2, and M3B2+ clusters. However, the fourth component does not arise from a bonding interaction but from polarization/hybridization. Considering the effect of Pauli repulsion in σ-space, the attractive covalent interaction in these molecules mainly comes from the two π-bonds. We further presented stable N-heterocyclic carbene (NHC) and triphenylphosphine (PPh3) ligands bound Li2B2(NHC)2 and Li2B2(PPh3)2 complexes. A comparative study of reactivity towards L = CO2, CO, and N2 between Li2B2(NHC)2 and B2(NHC)2 is also performed. L-Li2B2(NHC)2 is highly stable against L dissociation at room temperature for L = CO2 and CO, and the stability is markedly higher than that in L-B2(NHC)2. The larger B2→L π-backdonation in L-Li2B2(NHC)2 also makes L more activated than in L-B2(NHC)2.

O-Halogen-substituted arene linked selenium-N-heterocyclic carbene compounds induce significant cytotoxicity: Crystal structures and molecular docking studies

Synthesis of N-arylated benzimidazolium salts 1–2, as stable N-heterocyclic Carbene (NHC) σ- donor ligands, was carried out by simple, facile and high yielding method. Respective Se-NHC compounds 3–4 were synthesized in water at 100 °C in open air environment using elemental selenium as reactant. Various spectroscopic methods (FT-IR, 1H and 13C NMR) were used for characterization of the products. Single crystal of salt 2 was analyzed by x-rays crystallographic analysis. In-vitro anticancer studies of the products 1–4 were carried out against breast cancer cell line (MDA-MB-231), cervical cancer cell line from Henrietta Lacks (HeLa), human normal endothelial cell line (EA.hy926) and adenocarcinoma cell line (A549) using MTT assay and compared with a standard drug 5-Flourouracil (5FU). The products 1–4 showed IC50 values less than standard drug 5FU against MDA-MB-231. Against HeLa cell line, compound 2 and its complex 4 were more potent with IC50 value of 0.05 µM and 0.082 µM, respectively as compared with 5FU having IC50 value of 4.9 µM. Against A549 cell line the products 1–2 showed good IC50 values while 3 was inactive with very high value of IC50 and 4 also showed good IC50 value of 19.02 µM. Against EA.hy926 cell line, both the salts 1–2 showed more toxicity with lower IC50 values than selenium counterpart 3–4. The docked conformation of VEGFA, EGF, COX1 and HIF with active conformation of selenium compounds 3–4 and 5FU revealed numerous potential interactions. The selenium adducts 3–4 were better with lower binding energies than 5FU, however, both showed almost same values of inhibition constants and binding energies against all proteins. Also, inhibition constants of compounds 3–4 were almost equal but less than 5FU.

Green synthesis of selenium based N-heterocyclic carbene compounds; structural, in-vitro anticancer and molecular docking studies

Benzimidazolium salts (3−6) were synthesized as stable N-Heterocyclic Carbene (NHC) precursors and their selenium-NHC compounds/Selenones (7−10) were prepared using water as a solvent. Characterization of each of the synthesized compounds was carried out by various analytical and spectroscopic (FT-IR, 1H-, 13C NMR) methods. X-ray crystallographic analyses of single crystals obtained for salts 3 and 5 were carried out. Synthesized salts and their Se-NHCs were tested in-vitro for their anticancer potential against Cervical Cancer Cell line from Henrietta Lacks (HeLa), Breast cancer cell line (MDA-MB-231), Adenocarcinoma cell line (A549) and human normal endothelial cell line (EA.hy926). MTT assay was used for analysis and compared with standard drug 5-flourouracil. Benzimidazolium salts (3−6) and their selenium counter parts (7−10) were found potent anticancer agents. Salt 3–5 were found to be potent anticancer against HeLa with IC50 values 0.072, 0.017 and 0.241 μM, respectively, which are less than standard drug (4.9 μM). The Se-NHCs (7–10) had also shown significant anticancer potential against HeLa with IC50 values less than standard drug. Salts 3, 4 against EA.hy926, compounds 3,5,6, and 10 against MDA-MB-321, and compounds 4, 10 against A-549 cell line were found more potent anticancer agents with IC50 values less than standard drug. Molecular docking for (7−10) showed their good anti-angiogenic potential having low binding energy and significant inhibition constant values with VEGFA (vascular endothelial growth factor), EGF (human epidermal growth factor), COX1 (cyclooxygenase-1) and HIF (hypoxia inducible factor).

Planar-chiral 1,1'-diaminoferrocenes.

Planar-chiral homologues of 1,1'-diaminoferrocene, which bear a single additional substituent adjacent to one of the amino groups, are prepared as racemic mixtures in a few steps and in good yields from ferrocene. Various substituents relevant to steric shielding, coordination and further functionalisation are used, giving access to ferrocene-based planar-chiral diimines and diamines as well as stable N-heterocyclic carbenes and tetrylenes by transformations analogous to procedures established for 1,1'-diaminoferrocene.

N-Heterocyclic Carbenes–Cu

The electronic structures of N-heterocyclic carbenes (NHC) imidazolinylidene, thiazolinylidene, imidazolylidene, thiazolylidene, and 1,2,4-triazolylidene and their complexes with cuprous halides (CuX, X = Cl, Br, I) were investigated theoretically at the B3LYP/def2-SVP level. In contrast to other NHCs, imidazolylidene and 1,2,4-triazolylidene do not dimerize owing to the negligible coefficient of the vacant p-orbital at the carbene centre in their respective LUMOs. This is further supported by their greater thermodynamic and kinetic stabilities revealed by greater activation free energies and smaller standard free energies for their dimerization. Second-order perturbation interactions in the natural bond orbital (NBO) analysis of the NHCs indicate that six π electrons are delocalized in imidazolylidene, thiazolylidene, and 1,2,4-triazolylidene, conferring aromatic character and thereby enhancing their thermodynamic stability. NBO analysis reveals the existence of effective back bonding from a d orbital of Cu to the NHC, increasing the Wiberg bond index of the C–Cu bond to ~1.5. Owing to the large electronic chemical potential (μ) and high nucleophilicity indices, NHCs are able to transfer their electron density effectively to the cuprous halides having low μ values and high electrophilicity indices to yield stable NHC–CuI complexes. Large values of the Fukui function f(r) at the carbene centre of the NHCs and Cu atom of the NHC–CuI complexes indicate their softness. Imidazolylidene was found to be the softest, rationalizing wide use of this class of NHCs as ligands. The coordination of the NHCs to cuprous halides is either barrierless or has a very low activation free energy barrier. In the A3 reaction wherein NHC–Cu(I) complexes are used as catalyst, the reaction of NHC–CuI with phenylacetylene changes the latter into acetylide accompanied by raising the energy level of its HOMO considerably compared with the level of the uncomplexed alkyne, making its reaction with benzaldehyde barrierless.

Volatile and thermally stable silver pyrazolate complexes containing N-heterocyclic carbene ligands

Treatment of [Ag((CF3)2pz)]3 or [Ag(tBu,C3F7)pz)]3 (pz = pyrazolate) with various stable N-heterocyclic carbenes (NHC) afforded silver(I) complexes containing pyrazolate and NHC ligands in 10–81% crystalline yields. These complexes were analyzed by spectral and analytical techniques and by X-ray crystal structure determinations. The solid state structures showed monomeric, dimeric, or tetrameric formulations, depending upon the pyrazolate and NHC substituents. To evaluate their potential as thin film growth precursors, [Ag((CF3)2pz)]3, [Ag(tBu,C3F7)pz)]3, and the new complexes were evaluated by thermogravimetric analyses, sublimation studies, thermal decomposition temperatures, and solution reduction experiments with potential reducing agents. The decomposition temperatures were higher for complexes containing (CF3)2pz ligands (203 to 293 °C) than for those containing (tBu,C3F7)pz ligands (160 to 200 °C). The complexes sublimed between 110 and 140 °C at 0.2 Torr. Solution reactions of several complexes with aqueous hydrazine, 1,1-dimethylhydrazine, formic acid, and tBuNH2 led to the formation of silver metal. Several of the new complexes have promising precursor properties for use in thin film growth by the atomic layer deposition and chemical vapor deposition techniques.

Stable N-heterocyclic carbene derivatives of copper(i) and silver(i) containing radical anion redox active ligands

N-Heterocyclic carbene is a versatile ligand for the preparation of copper( i ) and silver( i ) derivatives bearing the radical anion forms of redox active o-benzoquinone and o-iminobenzoquinone. The paramagnetic three-coordinated copper( i ) and silver( i ) o-benzosemiquinone and o-iminobenzosemiquinone complexes were prepared and characterized by EPR spectroscopy and X-ray diffraction analysis.

Air-Stable Oxyallyl Patterns and a Switchable N-Heterocyclic Carbene.

Oxyallyl derivatives are typically elusive compounds. Even recently reported "stabilized" 1,3-diaminooxyallyl species are still highly reactive and have short lifetimes at room temperature. Herein, we report the synthesis and preliminary study of mesoionic pyrimidine derivatives that feature 1,3-bis(dimethylamino)oxyallyl patterns with an unprecedented level of stabilization. The latter are not only insensitive towards air and moisture, but they are also compatible with the formation of an ancillary stable N-heterocyclic carbene moiety. As the oxyallyl pattern is proton-responsive, it allows the reversible switching of the electronic properties of the carbene, as a ligand.

A Volatile Dialane Complex from Ring Expansion of an N-Heterocyclic Carbene and Its Use in the Thermal Atomic Layer Deposition of Aluminum Metal Films

Treatment of the stable N-heterocyclic carbene 1,3-di-tert-butylimidazolin-2-ylidene with 2 equiv of AlH3(NMe3) afforded the structurally unusual ring-expanded dialane complex 1 in 72% yield after ...

Mixture of Azolium Tetraphenylborate with Isopropylthioxanthone: A New Class of N-Heterocyclic Carbene (NHC) Photogenerator for Polyurethane, Polyester, and ROMP Polymers Synthesis.

In the search of smarter routes to control the conditions of N-heterocyclic carbene (NHCs) formation, a two-component air-stable NHC photogenerating system is reported. It relies on the irradiation at 365 nm of a mixture of 2-isopropylthioxanthone (ITX) with 1,3-bis(mesityl)imidazoli(ni)um tetraphenylborate. The photoinduced liberation of NHC is evidenced by reaction with a mesitoyl radical to form an NHC-radical adduct detectable by electron spin resonance spectroscopy. The NHC yield can be determined by 1 H NMR spectroscopy through the formation of a soluble and stable NHC-carbodiimide adduct. To deprotonate the azolium salt and liberate the NHC, a mechanism is proposed in which the role of base is played by ITX radical anion formed in situ by a primary photoinduced electron-transfer reaction between electronically excited ITX (oxidant) and BPh4 - (reductant). An NHC yield as high as 70 % is achieved upon starting with a stoichiometric ratio of ITX and azolium salt. Three different photoNHC-mediated polymerizations are described: synthesis of polyurethane and polyester by organocatalyzed step-growth polymerization and ring-opening copolymerization, respectively, and generation of polynorbornene by ring-opening metathesis polymerization using an NHC-coordinated Ru catalyst formed in situ.

Two Carbenes versus One in Magnesium Chemistry: Synthesis of Terminal Dihalide, Dialkyl, and Grignard Reagents

Substantial progress has been made in the coordination chemistry of main-group elements with neutral donor ligands, largely ushered in by the development of stable N-heterocyclic carbenes (NHCs). There is growing interest in the synthesis of well-defined coordination compounds containing s-block metals; however, examples of molecular compounds containing “normal” NHCs bound to magnesium remain relatively understudied. We report that NHCs react with magnesium halides, MgX2 (X = Cl, Br, I), to afford (IPr)MgCl2(THF) (1), [(IPr)MgCl2]2 (2), (sIPr)2MgCl2 (3), (sIPr)2MgBr2 (4), and (sIPr)2MgI2 (5), where IPr is 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidine and sIPr is 1,3-diisopropyl-4,5-dimethylimidizol-2-ylidine. Using the IPr ligand, weak NHC coordination and dynamic interaction with THF are observed in solution. In contrast, the coordination of two sIPr ligands results in higher purity, enhanced stability, and no observation of THF coordination. Dual carbene complexation with commercially available Mgn...

Dioxygen activation with stable N-heterocyclic carbenes.

Dioxygen activation with both cyclic (amino)(alkyl)carbenes and di(amino)carbenes at ambient temperature is described. Theoretical studies suggest that electron rearrangement from the doubly filled σ orbital of carbene carbon to its vacant p orbital through the π* antibonding orbital of 3O2 can be considered for Ccarbene-O bond formation.

Application of Ni(II) complexes of air stable Schiff base functionalized N-heterocyclic carbene ligands as catalysts for the transfer hydrogenation of aliphatic ketones

New air stable N-heterocyclic carbene functionalized Schiff base ligands (L) of the type 2-[-2-[3-(R)imidazol-1-yl]ethyliminomethyl]phenol [R = methyl (2), 2-pyridylmethyl (3)] were synthesized and characterized by NMR, IR, MS, and CHN analysis. Single crystal X-ray structural analysis of their Ni(II) complexes revealed square planar arrangement of the chelating ligands coordinated in tridentate (2, C^N^O) and tetradentate (3, N^C^N^O) modes around the metal. The three new isolated and fully characterized complexes were utilized as catalysts for the catalytic transfer hydrogenation of aliphatic ketones in 2-propanol as solvent and source of hydrogen. Based on 0.2 mol% catalyst concentration, the complexes showed activity for aliphatic ketones and 100% conversion (turnover number of 500) for cyclohexanone and all the aromatic ketones tested.

NHCs in Main Group Chemistry

Since the discovery of the first stable N-heterocyclic carbene (NHC) in the beginning of the 1990s, these divalent carbon species have become a common and available class of compounds, which have found numerous applications in academic and industrial research. Their important role as two-electron donor ligands, especially in transition metal chemistry and catalysis, is difficult to overestimate. In the past decade, there has been tremendous research attention given to the chemistry of low-coordinate main group element compounds. Significant progress has been achieved in stabilization and isolation of such species as Lewis acid/base adducts with highly tunable NHC ligands. This has allowed investigation of numerous novel types of compounds with unique electronic structures and opened new opportunities in the rational design of novel organic catalysts and materials. This Review gives a general overview of this research, basic synthetic approaches, key features of NHC-main group element adducts, and might be useful for the broad research community.

N-Heterocyclic Carbene Analogues of Thiele and Chichibabin Hydrocarbons.

Stable N-heterocyclic carbene analogues of Thiele and Chichibabin hydrocarbons, [(IPr)(C6 H4 )(IPr)] and [(IPr)(C6 H4 )2 (IPr)] (4 and 5, respectively; IPr=C{N(2,6-iPr2 C6 H3 )}2 CHCH), are reported. In a nickel-catalyzed double carbenylation of 1,4-Br2 C6 H4 and 4,4'-Br2 (C6 H4 )2 with IPr (1), [(IPr)(C6 H4 )(IPr)](Br)2 (2) and [(IPr)(C6 H4 )2 (IPr)](Br)2 (3) were generated, which respectively afforded 4 and 5 as crystalline solids upon reduction with KC8 . Experimental and computational studies support the semiquinoidal nature of 5 with a small singlet-triplet energy gap ΔES-T of 10.7 kcal mol-1 , whereas 4 features more quinoidal character with a rather large ΔES-T of 25.6 kcal mol-1 . In view of the low ΔES-T , 4 and 5 may be described as biradicaloids. Moreover, 5 has considerable (41 %) diradical character.

XPS-evidence for in-situ electrochemically-generated carbene formation

Stable N-heterocyclic carbenes (NHC) are a class of compounds that has attracted a huge amount of interest in the last decade. One way to prepare NHCs is through chemical or electrochemical reduction of 1,3-disubstituted imidazolium cations. We are presenting an in-situ electrochemical X-ray Photoelectron Spectroscopy (XPS) study where electrochemically reduced imidazolium cations lead to production of stable NHC. The electroactive imidazolium species is not only the reactant, but also part of the ionic liquid which serves as the electrolyte, the medium and the electroactive material. This allows us to directly probe the difference between the parent imidazolium ion and the NHC through the use of XPS. The interpretation of the results is supported by both observation of reversible redox peaks in the voltammogram and the density functional theory calculations.