Gold N-heterocyclic Carbene Complexes Research Articles

Sustainable Chemical Synthesis of 2,3-Dihydrobenzofurans/1,2,3-Trisubstituted Indanes in Water by Using a Permethylated β-Cyclodextrin-Tagged N-Heterocyclic Carbene–Gold Catalyst

AbstractAn environmentally friendly stereoselective synthesis of 2,3-dihydrobenzofurans and 1,2,3-trisubstituted indanes in water has been achieved by using a permethylated β-cyclodextrin-tagged N-heterocyclic carbene–gold complex. The gold catalyst can be recycled at least five times.

N-Heterocyclic Carbene Gold Complexes Active in Hydroamination and Hydration of Alkynes

Until the year 2000, gold compounds were considered catalytically inert. Subsequently, it was found that they are able to promote the nucleophilic attack on unsaturated substrates by forming an Au–π-system. The main limitation in the use of these catalytic systems is the ease with which they decompose, which is avoided by stabilization with an ancillary ligand. N-heterocyclic carbenes (NHCs), having interesting σ-donor capacities, are able to stabilize the gold complexes (Au (I/III) NHC), favoring the exploration of their catalytic activity. This review reports the state of the art (years 2007–2022) in the nucleophilic addition of amines (hydroamination) and water (hydration) to the terminal and internal alkynes catalyzed by N-heterocyclic carbene gold (I/III) complexes. These reactions are particularly interesting both because they are environmentally sustainable and because they lead to the production of important intermediates in the chemical and pharmaceutical industry. In fact, they have an atom economy of 100%, and lead to the formation of imines and enamines, as well as the formation of ketones and enols, all important scaffolds in the synthesis of bioactive molecules, drugs, heterocycles, polymers, and bulk and fine chemicals.

Access to Unsymmetrically Substituted Diaryl Gold N‐Acyclic Carbene (NAC) and N‐Heterocyclic Carbene (NHC) Complexes via the Isonitrile Route

AbstractA variety of unsymmetric diaryl gold N‐acyclic carbene (NAC) complexes was synthesized via the isonitrile route by three different methods: (a) solvent free in a melt, (b) mechanochemically and (c) in THF at room temperature. The latter method can also be used to synthesize unsaturated gold NHC complexes. These methods overall offer access to a broad array of new complexes and remove one of the previous limitations of the isonitrile route to NAC and NHC complexes of gold, namely the inability to react with the less nucleophilic aromatic amines. The new complexes also proved to be successful as pre‐catalysts in the gold‐catalyzed phenol synthesis.magnified image

Straightforward Synthesis of Indenes by Gold-Catalyzed Intramolecular Hydroalkylation of Ynamides.

An original and straightforward entry to polysubstituted indenes from readily available ynamides is reported. Upon reaction with a N-heterocyclic carbene-gold complex under mild conditions, activated keteniminium ions are generated whose unique electrophilicity triggers a [1,5]-hydride shift and a subsequent cyclization. The presence of an endocyclic enamide in the densely functionalized resulting indenes was shown to be especially useful and versatile, offering a range of opportunities for their further postfunctionalization.

Unprecedented Use of NHC Gold (I) Complexes as Catalysts for the Selective Oxidation of Ethane to Acetic Acid.

The highly efficient eco-friendly synthesis of acetic acid (40% yield) directly from ethane is achieved by the unprecedented use of N-heterocyclic carbene (NHC) and N-heterocyclic oxo-carbene (NHOC) gold(I) catalysts in mild conditions. This is a selective and promising protocol to generate directly acetic acid from ethane, in comparison with the two most used methods: (i) the three-step, capital- and energy-intensive process based on the high-temperature conversion of methane to acetic acid; (ii) the current industrial methanol carbonylation processes, based in iridium and expensive rhodium catalysts. Green metrics determinations highlight the environmental advantages of the new ethane oxidation procedure. Comparison with previous reported published catalysts is performed to highlight the features of this remarkable protocol.

Optimizing Catalyst and Reaction Conditions in Gold(I) Catalysis-Ligand Development.

This review considers phosphine and N-heterocyclic carbene complexes of gold(I) that are used as (pre)catalysts for a range of reactions in organic synthesis. These are divided according to the structure of the ligand, with the narrative focusing on studies that offer a quantitative comparison between the ligands and readily available or widely used existing systems.

Chiral N-heterocyclic Carbene Gold Complexes: Synthesis and Applications in Catalysis

N-Heterocyclic carbenes have found many applications in modern metal catalysis, due to the formation of stable metal complexes, and organocatalysis. Among a myriad of N-heterocyclic carbene metal complexes, gold complexes have gained a lot of attention due to their unique propensity for the activation of carbon-carbon multiple bonds, allowing many useful transformations of alkynes, allenes, and alkenes, inaccessible by other metal complexes. The present review summarizes synthetic efforts towards the preparation of chiral N-heterocyclic gold(I) complexes exhibiting C2 and C1 symmetry, as well as their applications in enantioselective catalysis. Finally, the emerging area of rare gold(III) complexes and their preliminary usage in asymmetric catalysis is also presented.

Steric and Electronic Effects in Gold N-Heterocyclic Carbene Complexes Revealed by Computational Analysis.

A computational analysis of a series of cationic and neutral gold imidazolylidene and benzimidizolylidene complexes is reported. The Bond Dissociation Energies of the various ligands in the complexes calculated at the PBE0‐D3/def2‐TZVP level of theory increase with increasing ligand volume, except for those of complexes containing t‐butyl‐substituted ligands, which are anomalously low particularly for the benzimidazolylidene species. Atoms in Molecules studies show the presence of a variety of weak intramolecular interactions, characterised by the presence of bond critical points with a range of different properties. Energy Decomposition Analysis and calculation of Electrostatic Surface Potentials indicate that some interactions are weakly attractive dispersion‐type interactions, while others are repulsive. The octanol/water partition coefficients (log P values) were calculated as a measure of the lipophilicities of the complexes and were found to increase with increasing volume.

Luminescent mechanochromism of gold N-heterocyclic carbene complexes with hypso- and bathochromic spectral shifts.

Two gold N-heterocyclic carbene complexes show contrasting luminescent mechanochromism behavior with hypso- and bathochromic spectral shifts. The distinct emission shifts upon mechanical stimulation can be explained by the aggregate-to-monomer transformation and intensified intermolecular interactions, respectively.

Amine-fnctionalized silver and gold N-heterocyclic carbene complexes: Synthesis, characterization and antitumor properties

Diisopropilamine-tethered benzimidazolium salts have been prepared as precursors for Ag(I)NHC and Au(I)NHC complexes. These NHC ligands were metallated with Ag2O on moderate conditions to give novel silver-NHC complexes. Gold-NHC complexes have been obtained by transmetalation using the silver-NHC precursor. The structures of all compounds were characterized by 1H NMR, 13C NMR, IR and elemental analysis techniques. The cytotoxic properties of the silver(I) and gold(I) complexes have been assessed in various human cancer lines, including cisplatin-sensitive and resistant cell. IC50 values of these four complexes were determined by the MTS based assay on three human cancer cell lines (SHSY5Y, HTC116 and HEP3B) and human healthy cell line (HF). These silver and gold N-heterocyclic carbene complexes have been highlighted metal-based cancer therapeutic agent with unique structures and functions. These strategies provide exciting opportunities for discovering new type metalodrug.

Regioselective Synthesis of Indene from 3‐Aryl Propargylic gem‐Dipivalates Catalyzed by N‐Heterocyclic Carbene Gold(I) Complexes

Abstract1‐Aryl‐3,3‐bis(pivaloyloxy)propynes can be converted in good to high yields into either 1,3‐ or 1,2‐bis(pivaloyloxy)indenes, depending on the N‐heterocyclic carbene (NHC) gold(I) hexafluoroantimonate catalyst used. Almost exclusive formation of 1,3‐di(oxycarbonyl)indene derivatives was achieved with cationic gold complexes containing the embracing N,N′‐1,3‐bis(9‐butylfluorenyl)benzimidazolylidene ligand (nBuFNHC). The regioselective issue of the reaction was rationalized by the specific spatial distribution of the steric bulk in the nBuFNHC ligand. In contrast, only modest selectivities in favor of 1,2‐disubstituted indenes were observed with more classical NHC gold complexes, the best selectivity being then obtained with N,N′‐1,3‐bis(2,6‐diisopropylphenyl)‐4,5‐dihydroimidazolylidene gold chloride (SIPrAuCl) as precatalyst.magnified image

Sugar‐Incorporated N‐Heterocyclic‐Carbene‐Containing Gold(I) Complexes: Synthesis, Characterization, and Cytotoxic Evaluation

A series of neutral and cationic gold(I) complexes bearing a glucopyranoside‐incorporated N‐heterocyclic carbene (NHC) ligand are synthetized and structurally characterized. Different secondary ligands (chlorido, phosphane, or sugar–NHC) are employed to tune the properties of the complexes. The antiproliferative effects of the compounds are evaluated against PC‐3 prostate cancer cells and a panel of human tumor cell lines. The activities of the phosphane complexes are comparable to that observed for cisplatin. The combined results provide further insights into the biological behavior of NHC–gold complexes.

A Structure‐Based Activity Study of Highly Active Unsymmetrically Substituted NHC Gold(I) Catalysts

AbstractFollowing the modular template synthesis using isonitriles, new unsymmetrically substituted five‐membered saturated N‐heterocyclic carbene (NHC) and N‐heterocyclic oxo‐carbene (NHOC) gold(I) complexes were prepared. With these species and already reported complexes, a detailed study concerning the catalytic activities of the complex classes available by the isonitrile route was conducted. The catalytic properties of twelve different types of NHOCs, saturated and unsaturated NHC gold(I) pre‐catalysts with different substituents, as well as one representative of a six‐membered NHC and one N‐acyclic carbene (NAC) gold(I) complex were analyzed by utilizing the phenol synthesis as a test reaction. For this reaction, the saturated NHC gold(I) complexes achieved higher conversions than the corresponding unsaturated NHCs and the NHOC systems. While unsaturated NHC complexes show higher catalytic activity during the initial phase of the conversion, due to a higher stability, higher turnover numbers (TONs) were obtained for the corresponding saturated systems. A cyclopentadecyl substituent at nitrogen turned out to be the privileged substituent for all of the unsymmetrical complexes. Furthermore, we detected that light exclusion can significantly increase the catalytic activity of NHC gold(I) complexes for phenol synthesis.magnified image

Characterization of Hydrophilic Gold(I) N-Heterocyclic Carbene (NHC) Complexes as Potent TrxR Inhibitors Using Biochemical and Mass Spectrometric Approaches.

We report here on the synthesis of a series of mono- and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8 > 9 > 10) against 2008 human ovarian cancer cells even after 1 h incubation. In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth. The compounds' inhibitory effects on TrxR and glutathione reductase (GR) were studied comparatively, using either the pure proteins or cancer cell extracts. The results show a strong and selective inhibitory effect of TrxR, specifically for the hydroxyl-functionalized NHC gold(I) complexes (8-10). Valuable information on the gold compounds' molecular reactivity with TrxR was gained using the BIAM (biotin-conjugated iodoacetamide) assay and performing competition experiments by mass spectrometry (MS). In good agreement, both techniques suggest the binding affinity of the mono(NHC) Au(I) complexes toward selenols and thiols. Notably, for the first time, bis-carbene formation from mono-carbenes in buffered solution could be observed by MS, which may provide new insights into the speciation mechanisms of bioactive Au(I) NHC complexes. Furthermore, the compounds' interactions with another relevant in cellulo target, namely telomeric G-quadruplex DNA-a higher-order DNA structure playing key roles in telomere function-was investigated by means of FRET melting assays. The lack of interactions with this type of nucleic acid secondary structure support the idea of selective targeting of the hydrophilic Au(I) NHC compounds toward proteins such as TrxR.

13C NMR Spectroscopy of N‐Heterocyclic Carbenes Can Selectively Probe σ Donation in Gold(I) Complexes

The Dewar-Chatt-Duncanson (DCD) model provides a successful theoretical framework to describe the nature of the chemical bond in transition-metal compounds and is especially useful in structural chemistry and catalysis. However, how to actually measure its constituents (substrate-to-metal donation and metal-to-substrate back-donation) is yet uncertain. Recently, we demonstrated that the DCD components can be neatly disentangled and the π back-donation component put in strict correlation with some experimental observables. In the present work we make a further crucial step forward, showing that, in a large set of charged and neutral N-heterocyclic carbene complexes of gold(I), a specific component of the NMR chemical shift tensor of the carbenic carbon provides a selective measure of the σ donation. This work opens the possibility of 1) to characterize unambiguously the electronic structure of a metal fragment (LAu(I)n+/0 in this case) by actually measuring its σ-withdrawing ability, 2) to quickly establish a comparative trend for the ligand trans effect, and 3) to achieve a more rigorous control of the ligand electronic effect, which is a key aspect for the design of new catalysts and metal complexes.

Coinage Metal Complexes of Bis-Alkynyl-Functionalized N-Heterocyclic Carbenes: Reactivity, Photophysical Properties, and Quantum Chemical Investigations.

Bis-phenylpropynyl-functionalized imidazolium salts and their corresponding gold and copper N-heterocyclic carbene (NHC) complexes were prepared in order to investigate their potential application for the synthesis of heterometallic coinage metal compounds. By transmetalation reactions with different precious metal sources, including copper and silver phenylacetylides [MCCPh]n (M=Cu, Ag), polynuclear compounds were obtained, which were further investigated for their photoluminescence properties. Additionally, one gold NHC complex was post-functionalized by autocatalytic hydration of the alkynyl side chains. Time-dependent DFT investigations of singlet electronic excitations in representative complexes revealed excited states of diverse character, as determined by the specific complex structure and metallophilic interactions.

N-heterocyclic carbene complexes of silver and gold as novel tools against breast cancer progression.

Metal carbenic complexes have received considerable attention in both the catalysis and biological fields for their potential applications in cancer and antimicrobial therapies. A small series of new silver and gold N-heterocyclic carbene complexes has been designed and synthesized. Among the tested complexes, one compound was particularly active in inhibiting anchorage-dependent and -independent breast cancer proliferation, and inducing cell apoptosis via a mitochondria-related process. The antitumor activity was associated to the transcriptional activation of the tumor suppressor gene p53 in an Sp1-dependent manner, as evidenced by biological and docking studies. Our results highlight the importance and the versatility of N-heterocyclic carbene complexes of gold and silver as useful tools against breast cancer progression.

Kinetics and Mechanism of Allene Racemization Catalyzed by a Gold N-Heterocyclic Carbene Complex

The kinetics of the racemization of 1,3-disubstituted allenes catalyzed by (IPr)AuOTf (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) has been investigated. The rate of gold-catalyzed allene racemization obeyed the following second-order rate law: rate = krac[allene][Au]. An analysis of the rate of the gold-catalyzed racemization of 1-aryl-1,2-butadienes as a function of allene electron donor ability established moderate depletion of electron density on the C1 allenyl carbon atom in the rate-limiting transition state for racemization. Analysis of the temperature dependence of the rate of racemization of 1-(p-tolyl)-1,2-butadiene established the activation parameters ΔH⧧ = 8.3 ± 1 kcal mol–1 and ΔS⧧ = −28 ± 4 eu. These observations were in accord with a mechanism for allene racemization involving turnover-limiting, intermolecular allene exchange followed by rapid allene stereomutation.

ChemInform Abstract: Anionic N‐Heterocyclic Carbene Complexes of Gold(I) as Precatalysts for Silver‐Free Cycloisomerization of Enynes.

ChemInformVolume 46, Issue 36 Preparative Organic Chemistry ChemInform Abstract: Anionic N-Heterocyclic Carbene Complexes of Gold(I) as Precatalysts for Silver-Free Cycloisomerization of Enynes. Stephanie Bastin, Stephanie Bastin Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorCecile Barthes, Cecile Barthes Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorNoel Lugan, Noel Lugan Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorGuy Lavigne, Guy Lavigne Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorVincent Cesar, Vincent Cesar Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this author Stephanie Bastin, Stephanie Bastin Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorCecile Barthes, Cecile Barthes Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorNoel Lugan, Noel Lugan Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorGuy Lavigne, Guy Lavigne Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this authorVincent Cesar, Vincent Cesar Lab. Chim. Coord., CNRS, Univ. Toulouse, F-31077 Toulouse, Fr.Search for more papers by this author First published: 20 August 2015 https://doi.org/10.1002/chin.201536036Read 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. Volume46, Issue36September, 2015 RelatedInformation

Quantum chemical insight into C–H⋯F bonding interactions between noncovalently bonded ion-pairs in N-heterocyclic carbene complexes of gold(I) [(NHC*)2Au]+[PF6]−and gold(III) [(NHC*)2AuCl2]+[PF6

New insights into ion-pairs interactions in N-heterocyclic carbene complexes of gold(I) [(NHC*)2Au]+[PF6]− and gold(III) [(NHC*)2AuCl2]+[PF6]− (NHC* = 1-methyl-2-pyridin-2-yl-2H-imidazo[1,5-a]pyridine-4-ylium hexafluorophosphate) have been investigated at DFT and DFT-D3(BJ) level of theory with density functionals BP86 and PBE with particular emphasis on the (i) bonding energy analysis between anion [PF6]− and cations [(NHC*)2Au]+, [(NHC*)2AuCl2]+ and (ii) effects of the non-covalent interactions between ion-pairs on the structures and the nature of Au–C(NHC*) bond in ionic complexes [(NHC*)2Au]+[PF6]−, [(NHC*)2AuCl2]+[PF6]− and as well as in cationic [(NHC*)2Au]+, [(NHC*)2AuCl2]+ complexes. The hydrogen-bonding interactions are stronger in Au(III) complex [(NHC*)2AuCl2]+ [PF6]− (II) than in Au(I) complex [(NHC*)2Au]+ [PF6]− (I). The carbene ligands donate about 0.20 electronic charge to the [PF6]− anion. The contributions of the electrostatic interaction ΔEelstat are significantly greater than the covalent bonding ΔEorb interaction. The bonding between ion-pairs has covalent character 17.4% in (I) and 14.5% in (II). The values of BDEs are depends on the choice of density functionals and follow the order BP86 < PBE < PBE-D3(BJ). The contribution of orbital interactions to the total attractive interactions for the Au–C(NHC*) bonds in cationic fragments [(NHC*)2Au]+ and [(NHC*)2AuCl2]+ varies from 27.8% to 36.7% and is higher for Au(III) complexes.