N-heterocyclic Carbene Copper Research Articles

A theophylline based copper N-heterocyclic carbene complex: synthesis and activity studies in green media

The synthesis of an easily accessible theophylline-derived copper complex with additional ammonium functionalization has been developed.

Copper N-Heterocyclic Carbene: A Catalyst for Aerobic Oxidation or Reduction Reactions.

Copper N-heterocyclic carbene complexes can be readily used as catalysts for both aerobic oxidation of alcohols to aldehydes and reduction of imines to amines. Our methodology is universal for aromatic substrates and shows versatile tolerance to potential cascade reactions. A one-pot tandem synthetic strategy could afford useful imines and secondary amines via an oxidation-reduction strategy.

ChemInform Abstract: Copper‐NHC Complexes in Catalysis

AbstractReview: 294 refs.

Novel copper compounds for vapor deposition: Characterization and thermolysis

The syntheses of new N-heterocyclic carbene—copper (I)–(X), where X is an easily interchangeable amide, including N-acetyl benzamide (1), diacetamide (2), and acetyl acetone (3), are described herein. These compounds have been shown by thermogravimetric analysis to have low onsets of volatility (<195 °C) and residual masses of 10.1%, 18.0%, and 5.8%, respectively. The trends in volatility, thermal stability, and reactivity in these three compounds will be the focus of this study to identify new precursors for copper metal deposition. Facile, nearly quantitative synthesis from commercially available starting material makes these precursors interesting candidates for future copper film deposition.

ChemInform Abstract: Asymmetric Catalysis with Silicon‐Based Cuprates: Enantio‐ and Regioselective Allylic Substitution of Linear Precursors.

An enantio- and regioselective allylic silylation of linear allylic phosphates that makes use of catalytically generated cuprate-type silicon nucleophiles is reported. The method relies on soft bis(triorganosilyl) zincs as silicon pronucleophiles that are prepared in situ from the corresponding hard lithium reagents by transmetalation with ZnCl2 . With a preformed chiral N-heterocyclic carbene-copper(I) complex as catalyst, exceedingly high enantiomeric excesses are achieved. The new method is superior to existing ones using a silicon-boron reagent as the source of the silicon nucleophile.

A Comparison of the Stability and Reactivity of Diamido- and Diaminocarbene Copper Alkoxide and Hydride Complexes.

The mononuclear N-heterocyclic carbene (NHC) copper alkoxide complexes [(6-NHC)CuOtBu] (6-NHC = 6-MesDAC (1), 6-Mes (2)) have been prepared by addition of the free carbenes to the tetrameric tert-butoxide precursor [Cu(OtBu)]4, or by protonolysis of [(6-NHC)CuMes] (6-NHC = 6-MesDAC (3), 6-Mes (4)) with tBuOH. In contrast to the relatively stable diaminocarbene complex 2, the diamidocarbene derivative 1 proved susceptible to both thermal and hydrolytic ring-opening reactions, the latter affording [(6-MesDAC)Cu(OC(O)CMe2C(O)N(H)Mes)(CNMes)] (6). The intermediacy of [(6-MesDAC)Cu(OH)] in this reaction was supported by the generation of Cu2O as an additional product. Attempts to generate an isolable copper hydride complex of the type [(6-MesDAC)CuH] by reaction of 1 with Et3SiH resulted instead in migratory insertion to generate [(6-MesDAC-H)Cu(P(p-tolyl)3)] (9) upon trapping by P(p-tolyl)3. Migratory insertion was also observed during attempts to prepare [(6-Mes)CuH], with [(6-Mes-H)Cu(6-Mes)] (10) isolated, following a reaction that was significantly slower than in the 6-MesDAC case. The longer lifetime of [(6-Mes)CuH] allowed it to be trapped stoichiometrically by alkyne, and also employed in the catalytic semi-reduction of alkynes and hydrosilylation of ketones.

Structure and spectroscopic properties of the dimeric copper(I) N-heterocyclic carbene complex [Cu₂(CNC(t-Bu))₂](PF₆)₂.

In recent years, the use of copper N-heterocyclic carbene (NHC) complexes has expanded to fields besides catalysis, namely medicinal chemistry and luminescence applications. In the latter case, multinuclear copper NHC compounds have attracted interest, however, the number of these complexes in the literature is still quite limited. Bis[μ-1,3-bis(3-tert-butylimidazolin-2-yliden-1-yl)pyridine]-1κ(4)C(2),N:N,C(2');2κ(4)C(2),N:N,C(2')-dicopper(I) bis(hexafluoridophosphate), [Cu2(C19H25N5)2](PF6)2, is a dimeric copper(I) complex bridged by two CNC, i.e. bis(N-heterocyclic carbene)pyridine, ligands. Each Cu(I) atom is almost linearly coordinated by two NHC ligands and interactions are observed between the pyridine N atoms and the metal centres, while no cuprophilic interactions were observed. Very strong absorption bands are evident in the UV-Vis spectrum at 236 and 274 nm, and an emission band is observed at 450 nm. The reported complex is a new example of a multinuclear copper NHC complex and a member of a compound class which has only rarely been reported.

Mechanism of Copper-Catalyzed Hydroalkylation of Alkynes: An Unexpected Role of Dinuclear Copper Complexes.

This article describes a mechanistic study of copper-catalyzed hydroalkylation of terminal alkynes. Relying on the established chemistry of N-heterocyclic carbene copper hydride (NHCCuH) complexes, we previously proposed that the hydroalkylation reaction proceeds by hydrocupration of an alkyne by NHCCuH followed by alkylation of the resulting alkenylcopper intermediate by an alkyl triflate. NHCCuH is regenerated from NHCCuOTf through substitution with CsF followed by transmetalation with silane. According to this proposal, NHCCuH must react with an alkyne faster than with an alkyl triflate to avoid reduction of the alkyl triflate. However, we have determined that NHCCuH reacts with alkyl triflates significantly faster than with terminal alkynes, strongly suggesting that the previously proposed mechanism is incorrect. Additionally, we have found that NHCCuOTf rapidly traps NHCCuX (X = F, H, alkenyl) complexes to produce (NHCCu)2(μ-X)(OTf) (X = F, H, alkenyl) complexes. In this article, we propose a new mechanism for hydroalkylation of alkynes that features dinuclear (NHCCu)2(μ-H)(OTf) (X = F, H, alkenyl) complexes as key catalytic intermediates. The results of our study establish feasible pathways for the formation of these intermediates, their ability to participate in the elementary steps of the proposed catalytic cycle, and their ability to serve as competent catalysts in the hydroalkylation reaction. We also provide evidence that the unusual reactivity of the dinuclear complexes is responsible for efficient hydroalkylation of alkynes without concomitant side reactions of the highly reactive alkyl triflates.

Asymmetric catalysis with silicon-based cuprates: enantio- and regioselective allylic substitution of linear precursors.

An enantio- and regioselective allylic silylation of linear allylic phosphates that makes use of catalytically generated cuprate-type silicon nucleophiles is reported. The method relies on soft bis(triorganosilyl) zincs as silicon pronucleophiles that are prepared in situ from the corresponding hard lithium reagents by transmetalation with ZnCl2 . With a preformed chiral N-heterocyclic carbene-copper(I) complex as catalyst, exceedingly high enantiomeric excesses are achieved. The new method is superior to existing ones using a silicon-boron reagent as the source of the silicon nucleophile.

N-heterocyclic carbene copper(I) catalysed N-methylation of amines using CO2.

The N-methylation of amines using CO2 and PhSiH3 as source of CH3 was efficiently performed using a N-heterocyclic carbene copper(i) complex. The methodology was found compatible with aromatic and aliphatic primary and secondary amines. Synthetic and computational studies have been carried out to support the proposed reaction mechanism for this transformation.

Electrochemical flow-reactor for expedient synthesis of copper-N-heterocyclic carbene complexes.

An electrochemical flow-cell for highly efficient and selective generation of Cu(I)-N-heterocyclic carbene complexes under neutral and ambient conditions is reported. The feasibility of the flow-cell is demonstrated through the electrochemical synthesis of [Cu(IMes)Cl] and subsequent in situ flow directly into hydrosilylation reactions, with equal efficiency to the purified catalyst.

Mechanism of trifluoromethylation reactions with well-defined NHC copper trifluoromethyl complexes and iodobenzene: A computational exploration

Abstract Computational calculation was performed to investigate the mechanism of trifluoromethylation reactions of iodobenzene with well-defined N -heterocyclic carbene (NHC)-supported Cu I trifluoromethyl complexes. Four proposed reaction pathways, namely σ-bond metathesis (BM), concerted oxidative addition–reductive elimination (OARE), iodine atom transfer (IAT) and single-electron transfer (SET), have been computed by density functional theory (DFT). The result indicated that the concerted OARE mechanism is favored among the four reaction pathways, suggesting the trifluoromethylation may occur via concerted OARE mechanism involving Ar–X oxidative addition to the Cu(I) center as the rate determining step.

Mechanism for the Carboxylative Coupling Reaction of a Terminal Alkyne, CO2, and an Allylic Chloride Catalyzed by the Cu(I) Complex: A DFT Study

DFT calculations have been carried out to study the detailed mechanisms for carboxylative-coupling reactions among terminal alkynes, allylic chlorides, and CO2 catalyzed by N-heterocyclic carbene copper(I) complex (IPr)CuCl. The competing cross-coupling reactions between terminal alkynes and allylic chlorides have also been investigated. The calculation results show that a base-assisted metathesis of (IPr)CuCl with PhC≡CH occurs as the first step to give the acetylide (IPr)Cu–C≡CPh, from which CO2 insertion and reaction with an allylic chloride molecule, respectively, lead to carboxylative-coupling and cross-coupling reactions. It was found that both the reactions of (IPr)Cu–C≡CPh and (IPr)CuOCOC≡CPh (a species derived from CO2 insertion) with an allylic chloride molecule occur through an SN2 substitution pathway. The two SN2 transition states (calculated for the carboxylative coupling and cross coupling) are the rate-determining transition states and show comparable stability. How the reaction conditions...

N-heterocyclic carbene copper complexes tethered to iron carbidocarbonyl clusters

The reactions of [Fe4C(CO)12(CuNCMe)x]x−2 (x=1, 2) with ImiPr·HBF4 (ImiPr=N,N′-bis(isopropyl)imidazol-2-ylidene) in the presence of NaH yielded [Fe4C(CO)12(CuImiPr)x]x−2. The hetero-substituted [Fe4C(CO)12(CuCl)(CuImiPr)]− was obtained by the deprotonation of the corresponding chloride salt. All products have been characterized by elemental analysis, NMR and single crystal X-ray diffraction analyses.

Use of Ring-Expanded Diamino- and Diamidocarbene Ligands in Copper Catalyzed Azide–Alkyne “Click” Reactions

The two-coordinate ring-expanded N-heterocyclic carbene copper(I) complexes [Cu(RE-NHC)2]+ (RE-NHC = 6-Mes, 7-o-Tol, 7-Mes) have been prepared and shown to be effective catalysts under neat conditions for the 1,3-dipolar cycloaddition of alkynes and azides. In contrast, the cationic diamidocarbene analogue [Cu(6-MesDAC)2]+ and the neutral species [(6-MesDAC)CuCl]2 and [(6-MesDAC)2(CuCl)3] show good activity when the catalysis is performed on water.

Synthesis and cytotoxicity studies of p-benzyl substituted NHC–copper(I) bromide derivatives

Two series of newly synthesised N-heterocyclic carbene–copper(I) bromide derivatives (1a–e and 2a–e) have been isolated and characterised.A series of highly biologically active symmetrically and un-symmetrically p-benzyl substituted imidazolium halides, reported previously by our group, was chosen as precursors for the series 2a–e.The imidazolium halides were reacted with silver oxide and then transmetallated to copper(I) to yield the corresponding N-heterocyclic carbene (NHC) copper(I) bromide complexes.The NHC–copper(I) bromide complexes 1a–e were found to be cytotoxic, giving IC50 values of 3.8 (±0.9), 7.4 (±2.4), 0.60 (±0.09), 13 (±4) and 42 (±7)μM, while NHC–copper(I) bromide complexes 2a–e showed IC50 values of 17 (±2), 21 (±3), 26 (±5), 68 (±7) and 61 (±10)μM against the breast cancer cell line MCF-7, respectively.The same NHC–copper(I) complexes 1a–e exhibited IC50 values of 5.6 (±0.9), 3.3 (±0.6), 0.65 (±0.08), 18 (±3) and 126 (±10)μM, while NHC–copper(I) bromide complexes 2a–e gave IC50 values of 17 (±2), 19 (±1), 18 (±1), 47 (±3) and 134 (±16)μM against the renal cancer cell-line Caki-1, respectively.

Trifluoromethyl-Promoted Oxidation of Fischer N-Heterocyclic Carbene Complexes by DMSO

A new protocol for trifluoromethyl-promoted oxidation of fischer-type N-Heterocyclic Carbene copper complexes has been developed by DMSO, which allows the preparation of imidazolinones from carbene complexes.

N-heterocyclic carbene copper(I) complex-catalyzed direct C–H thiolation of benzothiazoles

N-heterocyclic carbene (NHC) copper(I) complexes based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene catalyzed the direct C–H thiolation of benzothiazoles and benzoxazoles with aryl and alkyl thiols to give 2-aryl and 2-alkylthiobenzothiazoles in moderate-to-good yields. The NHC copper(I) complex [(IPr)CuI] was the most effective catalyst for the reaction among the NHC–Cu(I) complexes examined in this study.

ChemInform Abstract: Catalytic Boracarboxylation of Alkynes with Diborane and Carbon Dioxide by an N‐Heterocyclic Carbene Copper Catalyst.

ChemInformVolume 44, Issue 9 Organoelement Compounds ChemInform Abstract: Catalytic Boracarboxylation of Alkynes with Diborane and Carbon Dioxide by an N-Heterocyclic Carbene Copper Catalyst. Liang Zhang, Liang Zhang Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorJianhua Cheng, Jianhua Cheng Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorBeatrice Carry, Beatrice Carry Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorZhaomin Hou, Zhaomin Hou Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this author Liang Zhang, Liang Zhang Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorJianhua Cheng, Jianhua Cheng Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorBeatrice Carry, Beatrice Carry Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this authorZhaomin Hou, Zhaomin Hou Organomet. Chem. Lab., RIKEN, Adv. Sci. Inst., Wako 351-01, JapanSearch for more papers by this author First published: 05 March 2013 https://doi.org/10.1002/chin.201309172Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume44, Issue9February 26, 2013 RelatedInformation

Continuous Synthesis and Use of N-Heterocyclic Carbene Copper(I) Complexes from Insoluble Cu2O

It is demonstrated that homogeneous N-heterocyclic carbene-copper(I)-chloride complexes can be prepared continuously by flowing NHC precursors through a packed bed of solid Cu(2)O suspended in molecular sieves. The method enables the synthesis of a wide range of complexes including those that are challenging to prepare using standard approaches. Our strategy enables both sustained output of complex production for long-term catalytic reactions (greater than 5 h) and for generation of gram quantities for storage (greater than 1 g of complex in ~16 min).