N-heterocyclic Carbene Research Articles

Efficient Synthesis of Hydrobenzoin through NHC Catalysis: A Sustainable Approach for C−C Bond Formation

AbstractA facile and practical one‐pot synthesis of hydrobenzoin has been developed from the readily available aromatic aldehydes, under NHC catalysis. Basically, the present research elucidates a novel, sustainable approach for the synthesis of hydrobenzoin, capitalizing on the catalytic prowess of N‐heterocyclic carbene (NHC) and utilizing sodium borohydride (NaBH4) as an effective reducing partner in this one‐pot conversion. By harnessing the unique reactivity of NHCs, this methodology enables the efficient formation of C−C bonds, leading to the streamlined synthesis of hydrobenzoin with high yields while tolerating various functional groups. Furthermore, this catalytic system offers notable advantages in terms of atom economy, mild reaction conditions, and operational simplicity, making it a promising strategy for sustainable chemical synthesis. The detailed mechanistic insights provided herein shed light on the underlying catalytic pathways, facilitating a deeper understanding of the reaction mechanism. Overall, this study underscores the significant potential of NHC catalysis as a versatile tool for the sustainable synthesis of valuable organic compounds, thereby contributing to the advancement of green chemistry principles and the pursuit of environmentally benign chemical processes.

Accessing polyarene-fused ten-membered lactams via oxidative N-heterocyclic carbene (NHC)-catalyzed high-order [7 + 3] annulation

A new oxidative N-heterocyclic carbene (NHC)-catalyzed high-order [7 + 3] annulation reaction of γ-indolyl phenols as 1,7-dinucleophiles and α,β‐alkynals with the aid of Sc(OTf)3 is reported, enabling the highly regioselective access to unprecedented polyarene-fused ten-membered lactams bearing a bridged aryl-aryl-indole scaffold in moderate to good yields. This protocol demonstrates a broad substrate scope, good compatibility with substituents and complete regioselectivity, providing an organocatalytic modular synthetic strategy for creating medium-sized lactams.

Cooperative NHC and Photoredox Catalyzed Radical Aminoacylation of Alkenes to Tetrahydropyridazines.

Tetrahydropyridazines constitute an important structural motif found in numerous natural products and pharmaceutical compounds. Herein, we report an aminoacylation reaction of alkenes that enables the synthesis of 1,4,5,6-tetrahydropyridazines through cooperative N-heterocyclic carbene (NHC) and photoredox catalysis. This approach involves the 6-endo-trig cyclization of N-centered hydrazonyl radicals, generated via single-electron oxidation of hydrazones, followed by a radical-radical coupling step. The mild process tolerates a wide range of common functional groups and affords a variety of tetrahydropyridazines in moderate to high yields. Preliminary investigations using chiral NHC catalysts demonstrate the potential of this protocol for asymmetric radical reactions.

N-Heterocyclic Carbene-Derived Carbon Disulfide Radical Ligands for Palladium Diradicals.

N-heterocyclic carbenes (NHCs) are recognized for their ability to stabilize various main group radicals; however, NHC-derived, sulfur-based radicals remain rare. In this study, we successfully synthesized and characterized a series of palladium diradical complexes that featured new sulfur-based radical ligands from NHC-carbon disulfide adducts. Spectroscopic and computational characterizations of the palladium complexes confirmed the open-shell singlet ground state, which resulted from the antiferromagnetic coupling of two unpaired electrons on each ligand. Proton nuclear magnetic resonance relaxometry was used to experimentally confirm the presence of these unpaired electrons. Moreover, the redox behavior of the complexes was localized on the ligand center, confirming the redox activity of the ligands. The discovery of this sulfur-based, redox-active radical ligand underscores the versatility and significance of NHC-derived radicals, thereby expanding the repertoire of radical ligands and opening new avenues for advanced material and catalytic systems.

Ruthenium(II) complexes containing PEGylated N-heterocyclic carbene ligands for tunning biocompatibility in the fight against cancer

A synthetic procedure was designed for the preparation and characterization of Ag and Ru complexes containing NHC ligands functionalized with PEG fragments. Stability studies were conducted to gain insight of the species in water and other solvents like DMSO, or with reagents like imidazole as representative group for histidine amino acid. The presence of Cl atoms instead of H in the 4,5 positions of the N-heterocyclic carbene afforded higher water stability. The complexes containing PEG units must be considered inactive as anticancer agents. To enhance the anticancer activity of PEG-containing complexes, the balance between hydrophilicity and hydrophobicity was adjusted using a silane moiety, and an anionic carbosilane dendrimer as a lipophilic carrier.

The efficient metal- and halogen-free polymer catalyst for the intensification on CO2 cycloaddition

An environmentally friendly polymer catalyst (PAS) was synthesized via inverse emulsion polymerization using acrylic acid (AA) and 1-vinyl imidazole (VI) as monomers. The excellent catalytic activity of PAS was attributed to the synergistic effects of the carboxyl groups (-COOH) as hydrogen bond donors and N-heterocyclic carbene (NHCs) as electron donor, as well as the swelling properties of the polymer, which can enrich the substrate into the polymer network, increasing the contact between the substrate and active sites. Characterization results from thermogravimetric (TG) analysis and small-angle X-ray scattering (SAXS) showed that the excessive imidazole addition disrupted the polymer's chain-like structure, significantly reducing its swelling properties. And, the catalytic performance is influenced by both the amount of imidazole in PAS and the swelling properties of the polymer. Finally, the reaction mechanism of the CO2 cycloaddition reaction catalyzed by PAS was proposed and validated through density functional theory (DFT) calculations.

Enantioselective synthesis of saddle-shaped eight-membered lactones with inherent chirality via organocatalytic high-order annulation

Inherently chiral medium-ring derivatives have important applications in many research fields, such as materials science, molecular recognition, and asymmetric catalysis. However, the enantioselective assembly of these molecules, especially by organocatalytic strategies, remains a formidable challenge, and few methods are available. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) formal high-order (5 + 3) annulation of 1-(2-indolyl)naphthalen-2-ols with ynals. In the presence of an NHC pre-catalyst, base, Lewis acid and oxidant, this protocol enables the catalytic formation of C–C and C-O bonds, providing practical and facile access to an array of inherently chiral saddle-shaped eight-membered lactones featuring an oxocin-2-one scaffold with structural diversity in good efficiency and excellent enantiocontrol. Moreover, the scale-up preparation and representative late-stage transformations of the eight-membered lactones further demonstrate the application potential of this synthetic technology.

A convenient bottom up route to covalently anchor Pd(II)-PEPPSI on layered zirconium(IV) phosphonate: Efficient catalyst for Suzuki-Miyaura cross coupling of aryl chlorides

A rational and bottom-up route for assembling layered Zr(IV) phosphonate framework decorated with covalently anchored N-heterocyclic carbene NHC-Pd(II) fragment has been developed. Reaction of phosphonic acid functionalized Pd(II)-NHC precursor complex with ZrOCl2·8H2O provides easy access to a layered material with covalently anchored catalytically active Pd(II)-NHC sites. The Pd(II)-NHC functionalized Zr(IV) phosphonate showed enhanced catalytic activity in Suzuki-Miyaura cross coupling reaction of both aryl bromides and chlorides with aryl boronic acid, as compared to their homogeneous counterparts. The Zr(IV) phosphonate framework imparts remarkable robustness to the Pd(II)-NHC catalyst and allowed recycling of the catalyst up to nine catalytic cycles without any major loss of catalytic activity.

Novel Nonsymmetrically benzimidazolium salts and their silver(I)-N-heterocyclic carbene complexes: Synthesis, crystal structure, DFTstudies and anticancer activities

Due to the success of Ag-NHCs in biological applications, interest in the synthesis and applications of such compounds is increasing rapidly. Therefore, in this study, preparation and structural definition of silver(I)–NHC complexes were accomplished. These complexes were synthesized by combining a metal source, Ag2O, with imidazolium salts in dichloromethane. A comprehensive characterization process was carried out for both the ligands and their resulting complexes. This involved utilizing various analytical techniques, such as elemental analysis, LC-MS, FTIR and NMR spectroscopy. Further, structure of the 3 h complex was determined by X-ray crystallography. A single-crystal of 3 h shows that coordination geometry is a slightly distorted linear coordination geometry around the silver(I) center. Furthermore, our combined experimental and theoretical approach provided insights into the crystal structure, coordination geometry, and intermolecular interactions stabilizing the complex’s lattice. Density functional theory (DFT) optimization revealed its geometry, while time-dependent DFT (TD-DFT) calculations shed light on its optical properties. Furthemore the newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against three human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with Cisplatin as a reference drug.

Unveiling the ligand effects on Pt(Ⅱ) carbene complexes for rapid, efficient and narrow-spectra blue phosphorescence

Tetradentate Pt(II) complexes, comprising of benzoimidazolyl N-heterocyclic carbene (BI-NHC) coordination, have shown superior performance in blue phosphorescent organic light-emitting diodes (PhOLEDs). Here, four frame-structured complexes were synthesized to explore the intrinsic ligand effect for rapid, efficient and narrow-spectra blue phosphorescence through experimental analyses and theoretical calculations. We found carbazolylpridine (CzPy) chelating part in Pt(II) BI-NHC complexes dominates the phosphorescence with the suppression of metal-centered transition and electron-vibration coupling. Consequently, the CzPy chelated complexes (PtN-dip and PtN-dtb) achieved high luminescent efficiency, rapid radiative decay rate (kr) and narrow emission spectra. The peripheral substituent 2,6-di-iso-propylphenyl (dip) on NHC of PtN-dip constrains the molecule, significantly reducing the non-radiative decay rate (knr) and enhancing the efficiency. The 3,5-di-tert-butylphenyl (dtb) in PtN-dtb could enhances low-frequency vibration coupling that could expedite the excitons decay, resulting in higher kr and knr. This work unveils the intrinsic factors behind the ligand effects of Pt(II) BI-NHC based complexes, leading to a rapid, efficient and narrow-spectra phosphorescence.

(1,2,5,6-η)-Cyclo-octa-1,5-diene](1-ethyl-4-iso-butyl-1,2,4-triazol-5-yl-idene)(tri-phenyl-phosphane)iridium(I) tetra-fluorido-borate di-chloro-methane hemisolvate.

A new triazole-based N-heterocyclic carbene IrI cationic complex with a tetra-fluorido-borate counter-anion and hemi-solvating di-chloro-methane, [Ir(C8H12)(C8H15N3)(C18H15P)]BF4·0.5CH2Cl2, has been synthesized and structurally characterized. There are two independent ion pairs in the asymmetric unit and one di-chloro-methane solvent mol-ecule per two ion pairs. The cationic complex exhibits a distorted square-planar conformation around the IrI atom, formed by a bidentate cyclo-octa-1,5,diene (COD) ligand, a tri-phenyl-phosphane ligand, and an N-heterocyclic carbene (NHC). There are several close non-standard H⋯F hydrogen-bonding inter-actions that orient the tetra-fluorido-borate anions with respect to the IrI complex mol-ecules. The complex shows promising catalytic activity in transfer hydrogenation reactions. The structure was refined as a non-merohedral twin, and one of the COD mol-ecules is statistically disordered.

Asymmetric Intermolecular Conjugate Addition of 3-Substituted 2-Benzofuranones to Maleimides via Noncovalent NHC Catalysis

AbstractAn efficient N-heterocyclic carbene (NHC)-catalyzed asymmetric conjugate addition reaction to afford synthetically challenging benzofuranone derivatives having vicinal all-carbon quaternary and tertiary stereocenters is presented. The reaction operates solely through noncovalent interaction between a newly designed NHC and the substrates, providing access to a series of functionalized benzofuranones in good yields and with high ee values. The protocol applies to preparative-scale synthesis. A catalytic cycle involving a noncovalent substrate–NHC interaction is implicated in the process, based on a mechanistic control study.

Antimicrobial Activity of Anionic Bis(N-Heterocyclic Carbene) Silver Complexes

The antimicrobial properties of a series of anionic bis(carbene) silver complexes Na3[Ag(NHCR)2] were investigated (2a–2g and 2c′, where NHCR is a 2,2′-(imidazol-2-ylidene)dicarboxylate-type N-heterocyclic carbene). The complexes were synthesized by the interaction of imidazolium dicarboxylate compounds with silver oxide in the presence of aqueous sodium hydroxide. Complexes 2f,g were characterized analytically and spectroscopically, and the ligand precursor 1f and complexes 2c and 2g were structurally identified by X-ray diffraction methods. The anions of 2c and 2g, [Ag(NHCR)2]3−, showed a typical linear disposition of Ccarbene-Ag-Ccarbene atoms and an uncommonly eclipsed conformation of carbene ligands. The antimicrobial properties of complexes 2a–g, which contains chiral (2b–2e and 2c′) and non-chiral derivatives (2a,f,g), were evaluated against Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and a Gram-positive bacterium, Staphylococcus aureus. From the observed values of the minimal inhibitory concentration and minimal bactericidal concentration, complexes 2a and 2b showed the best antimicrobial activity against all strains. An interesting chirality–antimicrobial relationship was found, and eutomer 2c′ showed better activity than its enantiomer 2c against the three bacteria. Furthermore, these complexes were investigated experimentally and theoretically by 109Ag nuclear magnetic resonance, and the electronic and steric characteristics of the dianionic carbene ligands were also examined.

N-Heterocyclic Carbene Coordinated Cu Single Atoms on Poly(ionic Liquid) for Selective Electroreduction of CO 2 to CH 4 at High Current Density

N-Heterocyclic Carbene Coordinated Cu Single Atoms on Poly(ionic Liquid) for Selective Electroreduction of CO ₂ to CH ₄ at High Current Density

(CAAC)CuCl: A Competent Precatalyst for Carbonyl and Ester Hydrosilylation.

Cu-catalyzed carbonyl hydrosilylation involves a ligated "[(L)CuH]" as the active catalyst, where the ligand L has a crucial role toward the stability, stereoselectivity, and enhancement of the hydridicity. Strongly σ-donating N-heterocyclic carbenes (NHCs), their ring-expanded form, and an abnormal NHC as ligands have yielded robust and efficient Cu catalysts. However, cyclic(alkyl)(amino)carbenes (CAACs), despite being stronger σ-donors than NHCs and already having a salient Cu(I) chemistry, are yet to be reported as a similar ligand platform for this purpose. We establish here the familiar [(Me2CAAC)CuCl] as a powerful precatalyst in this regard. Additionally, it also catalyzes the more challenging ester hydrosilylation, which is a rare feat for a Cu catalyst. Apart from the stronger σ-donating ability, the more steric "openness" of CAACs than bulky NHCs also seems to be advantageous. To corroborate, three new (CAAC)CuCl complexes [(ArCH2,MeCAAC)CuCl] (Ar = Ph, 1-naphthyl, and 1-prenyl) are devised, where the effective steric around the copper is practically unaltered from the case of [(Me2CAAC)CuCl]. All three are equally active in carbonyl and ester hydrosilylation as [(Me2CAAC)CuCl]. Computation suggests the carbonyl insertion into a "(CAAC)Cu-H" as the rate-limiting step. To elucidate the involvement of a "(CAAC)CuH", "(PhCH2,MeCAAC)CuH" is generated in situ and is trapped as its BH3 adduct (PhCH2,MeCAAC)CuBH4.

Why is acyl fluoride favored in NHC/photoredox catalysis?

Recent advances in N-heterocyclic carbene (NHC)/photoredox catalyzed acylation have underlined the special reactivity of acyl fluoride compared with other acyl halides. Though safer and more convenient, acyl chloride is rarely used with NHC in known references. In a recent work, Studer et al. confirmed that acyl chloride and bromide are inactive in NHC/photoredox acylation, yet reason remains unknown. Herein, computational results showed that [1,2]-fluorine migration intermediate should be responsible for the unique role of acyl fluoride.

Anomalous Reaction Pathways to Methane Production in Photocatalytic Ethanol Oxidation.

Photocatalytic reduction reactions occasionally utilize sacrificial agents to scavenge photogenerated holes, thus enhancing the kinetics and efficiency of electron harvesting. However, exploring alternative hole-mediated oxidation reactions and their potential impact on photoredox processes is limited. This study investigates the products resulting from the oxidation of ethanol, a commonly used hole scavenger, and the underlying mechanisms involved. We examine a homogeneous eosin Y photoreaction scheme containing a Cu complex coordinated with an N-heterocyclic carbene, a combination often employed in CO2 conversion. Under visible-light excitation, this photosystem yields methane as an unusual product, alongside acetaldehyde and carbon monoxide. Mechanistic analysis reveals that ethanol undergoes a catalytic cascade involving oxidative processes, C-C bond cleavage, and intermolecular hydrogen atom transfer. Notably, the Lewis-acidic metal center of the Cu complex activates a novel pathway for ethanol oxidation. This work presents the influence of catalyst selection and reaction condition optimization on the emergence of new or unexpected catalytic processes.

Recent advances in the synthesis of highly substituted imidazolidines.

Imidazolidine is a saturated heterocycle with a cyclic aminal core that can be found in natural products and biologically active molecules. Additionally, these heterocyclic compounds have been utilized as chiral ligands, N-heterocyclic carbene precursors, and catalysts in organic synthesis. This review is an attempt to compile the literature of various synthetic procedures of highly substituted imidazolidines, chiral imidazolidines with high diastereoselectivities and enantioselectivities, bis-imidazolidines, and spiro-imidazolidines, as well as their pharmacological properties during the period from 1949 to 2023.

IPr# Complexes-Highly-Hindered, Sterically-Bulky Cu(I) and Ag(I) N-Heterocyclic Carbenes: Synthesis, Characterization, and Reactivity.

Metal-N-heterocyclic carbene (M-NHC) complexes are well-known as an important class of organometallic compounds widely used in transition-metal catalysis. Taking into account that the steric hindrance around the metal center is one of the major effects in M-NHC catalysis, the development of new, sterically hindered M-NHC complexes is an ongoing interest in this field of research. Herein, we report the synthesis and characterization of exceedingly sterically hindered, well-defined, air- and moisture-stable Cu(I) and Ag(I) complexes, [Cu(NHC)Cl] and [Ag(NHC)Cl], in the recently discovered IPr# family of ligands that hinge upon modular peralkylation of anilines. The complexes in both the BIAN and IPr families of ligands are reported. X-ray crystallographic analyses and computational studies were conducted to determine steric effects, Frontier molecular orbitals, and bond orders. The complexes were evaluated in the model hydroboration of the alkynes. We identified [Cu(BIAN-IPr#)Cl] and [Ag(BIAN-IPr#)Cl] as highly reactive catalysts with the reactivity outperforming the classical IPr and IPr*. Considering the attractive features of well-defined Cu(I)-NHC and Ag(I)-NHC complexes, this class of sterically bulky yet wingtip-flexible complexes will be of interest for catalytic processes in various areas of organic synthesis and catalysis.

Towards Nickel-NHC Fluoro Complexes-Synthesis of Imidazolium Fluorides and Their Reactions with Nickelocene.

While hundreds of complexes of the general formula [Ni(η5-C5H5)(NHC)(X)] exist (NHC = a N-heterocyclic carbene, X = Cl, Br, I), none is yet known with X = F. We attempted to prepare such a species by reacting nickelocene with imidazolium fluorides. Three imidazolium fluorides (ImH)+ F- [Im = (N,N'-bis-(R)-imidazolium: 1a, IMe, R = Me; 1b, IMes, R = 2,4,6-trimethylphenyl; 1c, IPr, R = 2,6-diisopropylphenyl)] were prepared and characterized by spectroscopic methods. In addition, the salts 1b [(IMesH)+ F-] and 1c [(IPrH)+ F-] were subjected single-crystal X-ray diffraction experiments. The reactions of these imidazolium fluorides with nickelocene did not lead to [Ni(η5-C5H5)(NHC)(F)] species. Instead, the reaction of 1a [(IMeH)+ F-] and 1b [(IMesH)+ F-] with nickelocene led to the salt 2 [Ni(η5-C5H5)(IMe)2]+ F- and to the square planar complex 3atrans-[NiF2(IMes)2] respectively. Both complexes were characterized spectroscopically and by single crystal X-ray diffraction. All four X-ray diffraction studies reveal hydrogen bonding and hydrogen interactions with the F atom or anion, and in some cases with solvent molecules of crystallization, and these phenomena are all discussed. Complex 2, in particular, exhibited a wide range of interesting H-bonded interactions in the solid state. Complexes 2 and 3a were tested as catalysts for Suzuki-Miyaura coupling but were not promising: complex 2 was inactive, and while 3a did indeed catalyze the reaction, it gave widely diverging results owing to its instability in solution.