Ru N-heterocyclic Carbene Research Articles

Gram-scale synthesis of carboxylic acids via catalytic acceptorless dehydrogenative coupling of alcohols and hydroxides at an ultralow Ru loading

Acceptorless dehydrogenative coupling (ADC) of alcohols and water/hydroxides is an emergent and graceful approach to produce carboxylic acids. Therefore, it is of high demand to develop active and practical catalysts/catalytic systems for this attractive transformation. Herein, we designed and fabricated a series of cyclometallated N-heterocyclic carbene-Ru (NHC-Ru) complexes via ligand tuning of [Ru-1], the superior complex in our previous work. Gratifyingly, gram-scale synthesis of carboxylic acids was efficiently enabled at an ultralow Ru loading (62.5 ppm) in open air. Moreover, effects of distinct ancillary NHC ligands and other parameters on this catalytic process were thoroughly studied, while further systematic studies were carried out to provide rationales for the activity trend of [Ru-1]-[Ru-7]. Finally, determination of quantitative green metrics illustrated that the present work exhibited superiority over representative literature reports. Hopefully, this study could provide valuable input for researchers who are engaging in metal-catalyzed ADC reactions.

Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation

Metal complexes can be considered a "paradigm of promiscuity" when it comes to their interactions with proteins. They often form adducts with a variety of donor atoms in an unselective manner. We have characterized the adducts formed between a series of isostructural N-heterocyclic carbene (NHC) complexes with Ru, Os, Rh, and Ir centers and the model protein hen egg white lysozyme by X-ray crystallography and mass spectrometry. Distinctive behavior for the metal compounds was observed with the more labile Ru and Rh complexes targeting mainly a surface l-histidine moiety through cleavage of p-cymene or NHC co-ligands, respectively. In contrast, the more inert Os and Ir derivatives were detected abundantly in an electronegative binding pocket after undergoing ligand exchange of a chlorido ligand for an amino acid side chain. Computational studies supported the binding profiles and hinted at the role of the protein microenvironment for metal complexes eliciting selectivity for specific binding sites on the protein.

Pyridine and pyrimidine functionalized half-sandwich Ru(II)-N heterocyclic carbene complexes: Synthesis, structures, spectra, electrochemistry and biological studies

New set of Ru-N-Heterocyclic Carbene (Ru-NHC) complexes 1a and 2a were synthesized from their ligand precursors 1-Methyl-2-pyridin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate (1) and 1-Methyl-2-pyrimidin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate (2). The molecules were characterized and their structures were investigated through single crystals X-ray diffraction. The overall coordination around the Ru center can be described as a half-sandwich geometry. Absorption spectra and electrochemical behavior of the complexes were also evaluated, supported by DFT analysis. The complexes were applied on lung (A549), colon (HCT116) and breast (MCF7) cancer cells to examine their in vitro cytotoxicity activity.

The catalytic activity of new iridium(I) N-heterocyclic carbene complexes for hydrogen transfer reaction of ketones

In this paper, the reaction of [Ir(COD)Cl]2 with in situ prepared Ag–N-heterocyclic carbene (NHC) complexes yields a series of [IrCl(COD)(NHC)] complexes. All compounds were fully characterized by 1H NMR, 13C NMR, and FT–IR spectroscopy. The manuscript focused on the preparation of new Ir–NHC complexes, characterization and catalytic behavior. A series of hydrogenation transfer reactions were performed to reveal the effects of the Ir–NHC complexes. The new Ir–NHC complexes of benzimidazole-2-ylidene are effective catalysts for the transfer of hydrogenation of different ketones, using i-PrOH as the source of hydrogen in the presence of KOH. The reactions were conducted at a substrate/catalyst/base (S/C/base) molar ratio of 1:0.001:2. Although all of the complexes are active catalysts for the transfer hydrogenation of ketones, moderate yields were obtained with acetylnaphthalene and conversion was not observed with very substituted ketones such as 2′,3′,4′,5′,6′-pentamethylacetophenone. It was observed that for transfer hydrogenation reactions Ir–NHC catalysts were more active, compared to Ru–NHC catalyzed studies performed by our team.

Pyridine and pyrimidine functionalized half-sandwich Ru(II)-N heterocyclic carbene complexes: Synthesis, structures, spectra, electrochemistry and biological studies

New set of Ru-N-Heterocyclic Carbene (Ru-NHC) complexes 1a and 2a were synthesized from their ligand precursors 1-Methyl-2-pyridin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate (1) and 1-Methyl-2-pyrimidin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate (2). The molecules were characterized and their structures were investigated through single crystals X-ray diffraction. The overall coordination around the Ru center can be described as a half-sandwich geometry. Absorption spectra and electrochemical behavior of the complexes were also evaluated, supported by DFT analysis. The complexes were applied on lung (A549), colon (HCT116) and breast (MCF7) cancer cells to examine their in vitro cytotoxicity activity.

Bis-tridentate N-Heterocyclic Carbene Ru(II) Complexes are Promising New Agents for Photodynamic Therapy.

Ruthenium(II) complexes developed for photodynamic therapy (PDT) are almost exclusively tris-bidentate systems with C2 or D3 symmetry. This is due to the fact that this structural framework commonly produces long-lived excited states, which, in turn, allow for the generation of large amounts of singlet oxygen (1O2) and other reactive oxygen species. Complexes containing tridentate ligands would be advantageous for biological applications as they are generally achiral (D2d or C2v symmetry), which eliminates the possibility of multiple isomers which could exhibit potentially different interactions with chiral biological entities. However, Ru(II) complexes containing tridentate ligands are rarely studied as candidates for photobiological applications, such as PDT, since they almost exclusively exhibit low quantum yields and very short excited-state lifetimes and, thus, are not capable of generating sufficient 1O2 or engaging in electron transfer reactions. Here, we report a proof-of-concept approach to make bis-tridentate Ru(II) complexes useful for PDT applications by altering their photophysical properties through the inclusion of N-heterocyclic carbene (NHC) ligands. Three NHC and two terpyridine ligands were studied to evaluate the effects of structural and photophysical modulations of bis-substituted Ru(II) complexes. The NHC complexes were found to have superior excited-state lifetimes, 1O2 production, and photocytotoxicity. To the best of our knowledge, these complexes are the most potent light-activated bis-tridentate complexes reported.

N‐Heterocyclic Carbene (NHC)‐Stabilized Ru0 Nanoparticles: In Situ Generation of an Efficient Transfer Hydrogenation Catalyst

Tethered and untethered ruthenium half-sandwich complexes were synthesized and characterized spectroscopically. X-ray crystallographic analysis of three untethered and two tethered Ru N-heterocyclic carbene (NHC) complexes were also carried out. These RuNHC complexes catalyze transfer hydrogenation of aromatic ketones in 2-propanol under reflux, optimally in the presence of (25 mol %) KOH. Under these conditions, the formation of 2-3 nm-sized Ru0 nanoparticles was detected by TEM measurements. A solid-state NMR investigation of the nanoparticles suggested that the NHC ligands were bound to the surface of the Ru nanoparticles (NPs). This base-promoted route to NHC-stabilized ruthenium nanoparticles directly from arene-tethered ruthenium-NHC complexes and from untethered ruthenium-NHC complexes is more convenient than previously known routes to NHC-stabilized Ru nanocatalysts. Similar catalytically active RuNPs were also generated from the reaction of a mixture of [RuCl2 (p-cymene)]2 and the NHC precursor with KOH in isopropanol under reflux. The transfer hydrogenation catalyzed by these NHC-stabilized RuNPs possess a high turnover number. The catalytic efficiency was significantly reduced if nanoparticles were exposed to air or allowed to aggregate and precipitate by cooling the reaction mixtures during the reaction.

Carbohydrate-functionalized N-heterocyclic carbene Ru(ii) complexes: synthesis, characterization and catalytic transfer hydrogenation activity.

Three Ru complexes containing carbohydrate/N-heterocyclic carbene hybrid ligands were synthesized that were comprised of a triazolylidene coordination site and a directly linked per-acetylated glucosyl (5Glc) or galactosyl unit (5Gal), or a glycosyl unit linked through an ethylene spacer (6). Electrochemical and UV-vis analysis indicate only minor perturbation of the electronic configuration of the metal center upon carbohydrate installation. Deprotection of the carbohydrate was accomplished under basic conditions to afford complexes that were stable in solution over several hours, but decomposed in the solid state. Complexes 5 and 6 were used as pre-catalysts for transfer hydrogenation of ketones under basic conditions, i.e. conditions that lead to in situ deprotection of the carbohydrate entity. The carbohydrate directly influences the catalytic activity of the metal center. Remotely linked carbohydrates (complex 6) induce significantly lower catalytic activity than directly linked carbohydrates (complexes 5Glc, 5Gal), while unfunctionalized triazolylidenes are an order of magnitude more active. These observations and substrate variations strongly suggest that substrate bonding is rate-limiting for transfer hydrogenation in these hybrid carbohydrate/triazolylidene systems.

Transfer hydrogenation of carbon dioxide and bicarbonate from glycerol under aqueous conditions.

The transfer hydrogenation of CO2 from glycerol to afford formic and lactic acid is a highly attractive path to valorizing two waste streams and is a significantly more thermodynamically favorable process than direct CO2 hydrogenation. We report the first homogeneous catalyst for this transformation consisting of a water-soluble Ru N-heterocyclic carbene complex. The catalyst affords lactic and formic acid selectively in the presence of a base at temperatures between 150 and 225 °C. Carbonate salts can also be utilized in place of CO2, affording the same products at higher rates.

A pH-controlled recyclable indolinooxazolidine tagged N-heterocyclic carbene Ru catalyst for olefin metathesis.

An indolinooxazolidine tagged N-heterocyclic carbene Ru olefin metathesis catalyst was synthesized and the molecular structure of this new Ru complex was determined by single crystal X-ray diffraction. This complex is a homogeneous catalyst and can be recovered by controlling the polarity of the indolinooxazolidine tag. Under acidic conditions the indolinooxazolidine tag exists as an open protonated form and under basic conditions the tag is in a closed form. The distribution of this catalyst in a two-phase system can be controlled by simply changing the pH, making the recovery of this catalyst easily obtainable.

Selective hydrogenation of nitriles to secondary amines catalyzed by a pyridyl-functionalized and alkenyl-tethered NHC–Ru(II) complex

A set of Co(III) and Ru(II) compounds are synthesized bearing pyridyl-functionalized and alkenyl-tethered N-heterocyclic carbene (NHC) ligand (L1). [CoIII(L1)3](PF6)3 (1) was synthesized by the reaction of [L1H]PF6, Co(OAc)2.4H2O, K2CO3 in tetrahydrofuran (THF) under refluxing condition. [RuIIL1(η6-p-cymene)Cl]PF6 (2) was synthesized via transmetallation method. For both compounds, the NHC ligand chelates the metal through carbene carbon and pyridyl nitrogen whereas the butenyl unit remains free. Compound 2 hydrogenates organic nitriles efficiently providing selectively secondary amines. In the presence of external amines, unsymmetrical secondary amines are also obtained.

Ruthenium(II) complexes incorporating salicylaldiminato-functionalized N-heterocyclic carbene ligands as efficient and versatile catalysts for hydration of organonitriles

We describe a new synthetic procedure for synthesis of ruthenium(II) complexes containing salicylaldiminato functionalized mixed N-heterocyclic carbene (NHC) ligand and phosphine co-ligand. The complexes (3a–3d) have been obtained in good to excellent yields by transmetalation from the corresponding Ag–NHC complexes (2a–2d) as carbene transfer reagents. All the [Ru–NHC] complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. The ligands 1a–1d show their versatility by switching to be O,N,C-chelating in these ruthenium(II) complexes. The resulting complexes have been evaluated as potential catalysts for the selective hydration of nitriles to primary amides, and related amide bond forming reactions, in environmentally friendly medium. The reaction tolerated ether, hydroxyl, nitro, bromo, formyl, pyridyl, benzyl and alkyl functional groups. The catalyst was stable for weeks and could be recovered and reused more than six times without significant loss of activity.

Novel ruthenium(II)–N-heterocyclic carbene complexes; synthesis, characterization and catalytic application

The synthesis of highly active ruthenium(II) catalyst based on N-heterocyclic carbene (NHC) bearing alkyl and aryl groups is reported. The complexes are easily handled in very good yields via synthesis of silver–NHC complexes and subsequent reaction with [RuCl2(p-cymene)]2 in dichloromethane (DCM) under N2 condition. All new compounds were characterized by LC-MSMS, elemental analysis, NMR spectroscopy and X-ray diffraction. With the development of a more efficient catalytic system for transfer hydrogenation of aryl ketones and aldehydes in mind, the catalytic performance of the Ru–NHC complexes for transfer hydrogenation was investigated.

Synthesis, coordination chemistry and reactivity of transition metal complexes supported by a chelating benzimidazolylidene carboxylate ligand

To construct the framework for a chelating, anionic benzimidazole-based N-heterocyclic carbene (NHC) ligand (1−), N-(3,5-dimethylphenyl)benzimidazole was reacted with 2-bromoacetic acid to yield the corresponding benzimidazolium [1H2][Br]. Double deprotonation followed by metallation of [1H2][Br] with Ag2O produced the Ag–NHC complex [Ag(1)]n (2), which exhibited good solubility in organic solvents despite its multinuclear nature. Crystallographic analysis of 2 revealed a dodecametallic structure (n=12) comprising mononuclear [Ag(1)] and dinuclear [Ag2(1)2] subunits, the latter of which featured close Ag⋯Ag contacts. Transmetallation of 1− from Ag to Ru via the reaction of [RuCl(η6-cymene)(μ–Cl)]2 with 2 afforded the Ru–NHC complex [RuCl(1)(η6-cymene)] (3), which demonstrated catalytic activity for transfer hydrogenation of CO, CN and CC bonds using isopropanol as the H2 source.

4-Vinylbenzyl-substituted silver(I) N-heterocyclic carbene complexes and ruthenium(II) N-heterocyclic carbene complexes: synthesis and transfer hydrogenation of ketones

4-Vinylbenzyl-substituted Ag(I) N-heterocyclic carbene (NHC) complexes and Ru(II) NHC complexes have been synthesized. The Ag(I) complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II) complexes were prepared from Ag(I) NHC complexes by transmetallation. The six 4-Vinylbenzyl-substituted Ag(I) NHC complexes and six 4-Vinylbenzyl-substituted Ru(II) NHC complexes have been characterized by spectroscopic techniques and elemental analyses. The Ru(II) NHC complexes show catalytic activity for the transfer hydrogenation of ketones.

New Aqua N-Heterocyclic Carbene Ru(II) Complexes with Two-Electron Process as Selective Epoxidation Catalysts: An Evaluation of Geometrical and Electronic Effects

New ruthenium complexes with general formula [Ru(II)(T)(CN-Me)X](n+) (X = Cl(-) or H2O; T = 2,2':6',2″-terpyridine, trpy, or N,N-bis(2-pyridyl)ethylamine, bpea; CN-Me = N-methyl-N'-2-pyridylimidazolium) have been prepared. The complexes obtained have been characterized in solution by spectroscopic (1D- and 2D-NMR and UV-vis) techniques, mass spectrometry, and elemental analysis. The chloro complexes have also been characterized by X-ray diffraction analysis. The redox properties of all the compounds were studied by CV revealing, for the reported Ru-OH2 complexes, bielectronic Ru(IV/II) redox processes throughout a wide pH range. The catalytic activity of aquo complexes was evaluated in the epoxidation of olefins using PhIO as oxidant, displaying in general good yields and high selectivities for the epoxide product. The influence of electronic and geometrical factors on the spectroscopic and electrochemical properties as well as on the catalytic activity is discussed.

Proton-Induced Dynamic Equilibrium between Cyclometalated Ruthenium rNHC (Remote N-Heterocyclic Carbene) Tautomers with an NAD+/NADH Function

Cyclometalated ruthenium(II) complexes having acridine moieties have been synthesized and characterized by spectroscopic methods. Protonation of the acridine nitrogen of the ruthenium(II) complexes not only causes dynamic equilibrium with remote N-heterocyclic carbene Ru═C complexes but also generates the NAD(+)/NADH redox function driven by a proton-coupled two-electron transfer accompanying a reversible C-H bond formation in the pyridinium ring.

Ligand‐Controlled Highly Regioselective and Asymmetric Hydrogenation of Quinoxalines Catalyzed by Ruthenium N‐Heterocyclic Carbene Complexes

Inflating flat bicycles: Proper choice of the N-heterocyclic carbene (NHC) ligand in Ru NHC complexes allows the completely regioselective ligand-controlled hydrogenation of either the heterocyclic or the carbocyclic ring of a substituted quinoxaline in quantitative yields. Chiral NHC ligands allow the challenging asymmetric hydrogenation of the carbocyclic ring of quinoxalines, yielding enantioenriched 5,6,7,8-tetrahydroquinoxalines with an enantiomeric ratio of up to 94:6.

Theoretical characterization of a Ru N-Heterocyclic Carbene derivative of a polyoxometalate. Enhanced π-interaction in oxide supported TM-organic linkages

The electronic structure of the N-heterocyclic carbene (NHC) functionalized polyoxometalate [K(PW(9)O(34))(2)(cis-WO(2))(cis-RuLMe(2))](12-) (1) is studied computationally; and its Ru-NHC bonding situation is compared with other monometallic Ru-NHC complexes, as well as other representative carbene complexes. The DFT analysis further supports the low spin configuration, S = ½, as the ground state, as the unoccupied d ruthenium orbitals are high in energy and mixed with the d-type orbitals of W. We gauge the TM-carbene bonding nature by means of atoms in molecules (AIM) quantum theory and a modified version of energy decomposition analysis (EDA) based on orbital deletion. According to the calculations, the NCH ligand in POM derivative 1 is more tightly bonded than in its analogous neutral monometallic Ru-NHC complexes. This is manifested in a higher electron density ρ(r) at the bond critical point (bcp) between Ru and the carbene carbon atoms. The energetic contribution of σ-donation is similar for all Ru-NHC complexes, and significantly higher than for Fischer-type carbene complex, in agreement with the description of the N-heterocyclic carbene ligand as a strong σ-donor. Among the studied Ru-NHC complexes, the POM derivative 1 shows the largest π-back-donation ability, explaining the observed short Ru-C(carbene) bond distance and the calculated high interaction energy. The POM framework acting as ligand makes the ruthenium d electrons more loose via orbital mixing and promotes the back-donation to the ligand.

A nurse-managed hypertension follow-up clinic within a large multispecialty group—A five-year experiment: James C. Dahl, St. Louis Park Medical Center, 5000 West 39th Street, St. Louis Park, Minnesota 55416

The clinical success of platinum-based chemotherapeutic agents was of enormous impact on the discovery of novel metal N-heterocyclic carbene (NHC) complexes as potential anti-cancer drugs. During the last years, the research on cytotoxic transition metal (e.g. Ag, Au, Pt, Pd, Cu, Hg, Ru, Os, Rh and Ir) NHC complexes was successful and the results are remarkable. In this review, we provide an update on the recent advances in this direction, which reflects new discoveries since the publication of our previous review. The anti-tumor properties along with the mechanisms of action for these complexes as well as possible structure–activity relationships are discussed.