Nickel N-heterocyclic Carbene Complexes Research Articles

Synthesis, characterization, in vitro antimicrobial and anticancer studies of new platinum N-heterocyclic carbene (NHC) complexes and unexpected nickel complexes

A series of bidendate pyridine-functionalized metal N-heterocyclic carbene (NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert-butyl) had been prepared from silver oxide-mediated transmetalation method. The basic backbone of the NHC ligands were prepared in two stepwise reactions: reduction of the commercially available 2-benzoylpyridine, followed by halogenation to yield 2-(chloro(phenyl)methyl)pyridine. Subsequent reactions with different imidazoles gave the desired imidazolium salts (or NHC precursors) with different R groups at the N wingtip (R = Me, Ph, t-Bu). Transmetalation of the imidazolium salts into platinum NHC complexes were achieved by using Ag2O mediated method with Pt(cod)Cl2 as the transmetalating agent. On the other hand, nickel NHC complexes were obtained via one pot synthesis method with nickel chloride as the transmetalating agent and reflux in the presence of a base. Following recrystallisation, the molecular structure of Pt NHC complex ( ± )-5a had been successfully elucidated via single crystal X ray diffraction (XRD) analysis. The six-membered ring of the platinum NHC complexes adopted a boat conformation with the phenyl ring arranged at the axial position. Meanwhile, two unexpected nickel complexes, i.e. a simple nickel coordination complex and a nickelate complex, were obtained and studied using XRD. These Pt NHC complexes and unexpected Ni complexes were evaluated for their in vitro antimicrobial and anticancer activities against a panel of pathogenic microorganisms and three selected human cancer cell lines, including breast (MCF7), colon (HCT116) and oral (H103) cancer cells. Generally, the Pt NHC complexes displayed enhanced antimicrobial activities upon coordination to metals, as compared to the corresponding imidazolium salts i.e. NHC precursors, with minimum inhibitory concentration (MIC) values in micromolar (μM) range. A couple of platinum NHC complexes synthesized exhibited antimicrobial activities with MIC as low as 2 μM, which are comparable to silver NHC complexes with renowned antimicrobial profiles. Similarly, upon coordination to the metals, the cytotoxic effects of the platinum NHC complexes increased significantly as compared to the imidazolium salts. Among all, platinum NHC complex (±)-5c displayed significant cytotoxicities towards the cancer cells with IC50 values that are two to three times lower than that of the anticancer drug cisplatin. In summary, evidences for influence of both wingtip substituents and metals on the biological activities of the complexes have been found.

Benzothiazole Nickelation: An Obstacle to the Catalytic Arylation of Azoles by Cyclopentadienyl Nickel N-Heterocyclic Carbene Complexes

NiCp†L(NHC)](+) complexes (Cp† = Cp (η5-C5H5), Cp* (η5-C5Me5); NHC = N-heterocyclic carbene; L = Cl− or NCMe) have been tested as pre-catalysts for the direct arylation of benzothiazole in the presence of an alkoxide. Only the pentamethylcyclopentadienyl derivative, [NiCp*Cl(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenylimidazol-2-ylidene), enabled low conversion to the desired coupling product with phenyl iodide as the electrophilic coupling partner. In contrast, all cyclopentadienyl complexes proved to be inactive. 1H NMR studies of the “catalytic” reaction mixtures demonstrate that they cleanly convert to an unreactive C(2)-benzothiazolyl derivative, whose identity has been confirmed by an independent synthesis and characterization. The latter constitutes a potential energy well that quenches all further reactivity, and provides a rare example of C(2)-metallated azolyl complex.

Mass spectrometric support for a bifunctional catalysis mechanism for the base-free Michael addition by a nickel N-heterocyclic carbene complex: Detection of the catalytic intermediates

A bifunctional catalysis mechanism for an asymmetric base-free Michael addition reaction mediated by a chiral nickel N-heterocyclic carbene complex has been corroborated by mass spectrometry. In particular, for the first time, all of the intermediates for a proposed catalytic cycle for an asymmetric base-free Michael addition of α-methyl cyano ester and cyclic β-keto ester substrates with various activated olefins as catalyzed by a chiral nickel N-heterocyclic carbene complex namely, {[(1-R1-3-R2-acetamido)imidazol-2-ylidene][(1-R1-3-R2-acetamidato)imidazol-2-ylidene]}NiOH [R1=(1S,2S,5R)-menthyl, R2=2,6-i-Pr2C6H3 (3)] have been detected by Electrospray Ionization Mass Spectrometry (ESI-MS).

Synthesis of inexpensive chiral half-sandwich nickel N-heterocyclic carbene complexes: X-ray diffraction study of the D-menthyl-functionalized complex [Ni(iPr2Ph-NHC-CH2OMent)ClCp

The imidazolium salts, 1-(2,4,6-trimethylphenyl)-3-[(1R,2S,5R)-(−)-menthoxymethyl]imidazolium chloride (Mes-NHC-CH2OMent·HCl) (1a) and 1-(2,6-diisopropylphenyl)-3-[(1R,2S,5R)-(−)-menthoxymethyl]imidazolium chloride (iPr2Ph-NHC-CH2OMent·HCl) (1b), are readily accessible from inexpensive (1R,2S,5R)-(−)-menthol. They react with nickelocene to give two new chiral nickel-N-heterocyclic carbene (NHC) complexes, [Ni(Mes-NHC-CH2OMent)ClCp] (2a) and [Ni(iPr2Ph-NHC-CH2OMent)ClCp] (2b), in good yields. The new complexes were fully characterized by standard spectroscopic techniques and by a single crystal X-ray diffraction study on complex 2b. Complex 2b crystallizes in the chiral spacegroup P1, with two independent molecules in the unit cell, which are slightly different from each other. Preliminary studies show that these complexes are effective catalysts for the hydrosilylation of ketones. However no chiral induction was observed.

ChemInform Abstract: Nickel N‐Heterocyclic Carbene Complexes and Their Utility in Homogeneous Catalysis

AbstractReview: 570 refs.

ChemInform Abstract: Nickel N‐Heterocyclic Carbene‐Catalyzed C—C Bond Formation: Reactions and Mechanistic Aspects

AbstractReview: 165 refs.

Nickel N-Heterocyclic Carbene-Catalyzed C–C Bond Formation: Reactions and Mechanistic Aspects

The chemistry of nickel N-heterocyclic carbene complexes is a research area that has blossomed over the last 10 years, and a large number of new complexes with a variety of architectural motifs are now known. The evolution of this chemistry has led to increasing applications of these complexes in catalytic bond formation. The rapid expansion of this field now calls for a review of the kinds of reactions that are catalyzed and a summary of the state of the art at this time. As the breadth of reactions catalyzed by such complexes is vast, this review specifically targets catalytic C–C bond formation, in particular C–C cross-couplings and C–C couplings via C–H bond activation, mediated by nickel–N-heterocyclic carbene complexes. A special emphasis is placed on mechanistic data, because this allows possible new insights into catalyst improvement.

An insight into a base-free Michael addition reaction as catalyzed by a bifunctional nickel N-heterocyclic carbene complex using density functional theory studies

A proposed catalytic pathway for a base-free Michael addition reaction mediated by a N/O-functionalized N-heterocyclic carbene (NHC) based bifunctional nickel precatalyst has been probed using density functional theory (DFT) studies. In particular, the base-free Michael addition of a β-dicarbonyl compound namely, 2-acetyl-cyclopentanone (a) with methyl vinyl ketone (b) as catalyzed by a representative bifunctional nickel precatalyst viz. [1-(Me)-3-N-(methylacetamido)imidazol-2-ylidene]2Ni (A) has been investigated. The modeling studies reveal that the nucleophilic attack of a metal bound enolate moiety of a 1,3-dicarbonyl adduct species (B) to the approaching activated olefinic substrate, methyl vinyl ketone (b), is the crucial rate-limiting step of the reaction yielding a Michael addition product adduct species (C). Interestingly, the subsequent intramolecular rearrangement of (C) to a different O-bound intermediate (D) exhibit nearly equal activation barrier.

Suzuki–Miyaura cross-coupling of bulky anthracenyl carboxylates by using pincer nickel N-heterocyclic carbene complexes: an efficient protocol to access fluorescent anthracene derivatives

A series of fluorescent (hetero)-aryl substituted anthracene derivatives were readily accessible from the corresponding bulky anthracen-9-yl carboxylates via Suzuki-Miyaura cross-coupling reactions by using pincer nickel N-heterocyclic carbene complex even at the catalyst loading as low as 0.1 mol% in the presence of catalytic amounts of PCy3.

Intramolecular Nitrile C–H Bond Activation in Nickel NHC Complexes: A Route to New Nickelacycles

Cyclopentadienyl N-heterocyclic carbene (NHC) nickel complexes of general formula [Ni(NHC)XCp] (NHC = 1-(propylnitrile)-3-methylimidazol-2-ylidene, 1-(2,4,6-trimethylphenyl)-3-(butylnitrile)imidazol-2-ylidene, 1-(2,4,6-trimethylphenyl)-3-(pentylnitrile)imidazol-2-ylidene, 1-(2,4,6-trimethylphenyl)-3-(hexylnitrile)imidazol-2-ylidene; X = Cl, Br, I; Cp = η5-C5H5), which bear an alkylnitrile side chain attached to one of the nitrogen atoms of the NHC ring, were prepared by the direct reaction of nickelocene with the corresponding imidazolium salts (NHC·HX). The new complexes [Ni{Me-NHC-(CH2)2CN}ICp] (1a), [Ni{Mes-NHC-(CH2)3CN}ClCp] (1b), [Ni{Mes-NHC-(CH2)4CN}ICp] (1c), and [Ni{Mes-NHC-(CH2)5CN}BrCp] (1d) were obtained in good yields and were fully characterized by standard spectroscopic techniques and elemental analyses and, in the cases of 1a,b, by single-crystal X-ray crystallography. Structural studies established their two-legged piano-stool geometry. The cationic derivatives [Ni{Mes-NHC-(CH2)nCN}(NCMe)Cp]+ (2b–d; n = 3–5) were prepared from the reaction of their neutral homologues 1b−d with KPF6 in acetonitrile at room temperature. Upon treatment of the neutral complexes 1 or of the cationic compounds 2 with KO-t-Bu, a C–H bond α to the nitrile group in each molecule underwent a base-promoted C–H activation and the new nickelacyclic complexes [Ni{Me-NHC-CH2CH(CN)}Cp] (3a) and [Ni{Mes-NHC-(CH2)nCH(CN)}Cp] (3b–d; n = 2–4) were obtained. All of these metallacycles contain Ni–C σ-bonds, and their synthesis generated a new asymmetric carbon center. The cyclic complexes 3 were fully characterized by 1H and 13C NMR spectroscopy, IR spectroscopy, and elemental analyses. The structures of complexes 3b and 3d, which contain six- and eight-membered metallacyclic rings, respectively, were determined by single-crystal X-ray diffraction studies. DFT studies, carried out to probe the mechanism of these cyclonickelation reactions, indicated that the mechanism of formation of these nickelacycles was similar to that observed for the formation of cyanomethyl ligands from coordinated acetonitrile. Nevertheless, the base deprotonation of an α-C–H ligand in a side arm, while thermodynamically comparable to that of a simultaneously coordinated acetonitrile ligand, is kinetically favored, and this leads to the formation of nickelacycles rather than cyanomethyl complexes in the case of the base-assisted activation of the cationic complexes 2.

Nickel(II) Complexes of Bidentate N‐Heterocyclic Carbene/Phosphine Ligands: Efficient Catalysts for Suzuki Coupling of Aryl Chlorides.

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Nickel(II) Complexes of Bidentate N‐Heterocyclic Carbene/Phosphine Ligands: Efficient Catalysts for Suzuki Coupling of Aryl Chlorides

Nickel(II) complexes of bidentate N-heterocyclic carbene (NHC)/phosphane ligand L were prepared and structurally characterized. Unlike palladium, which forms [PdCl(2)(L)], the stable nickel product isolated is the ionic [Ni(L)(2)]Cl(2). These Ni(II) complexes are highly robust in air. Among different N-substituents on the ligand framework, the nickel complex of ligand L bearing N-1-naphthylmethyl groups (2 a) is a highly effective catalyst for Suzuki cross-coupling between phenylboronic acid and a range of aryl halides, including unreactive aryl chlorides. The activities of 2 a are largely superior to those of other reported nickel NHC complexes and their palladium counterparts. Unlike the previously reported [NiCl(2)(dppe)] (dppe=1,2-bis(diphenylphosphino)ethane), 2 a can effectively catalyze the cross-coupling reaction without the need for a catalytic amount of PPh(3), and this suggests that the PPh(2) functionality of hybrid NHC ligand L can partially take on the role of free PPh(3). However, for unreactive aryl chlorides at low catalyst loading, the presence of PPh(3) accelerates the reaction.