IPr*F - Highly Hindered, Fluorinated N-Heterocyclic Carbenes.

The introduction of fluorine atom has attracted considerable interest in molecular design owing to the high electronegativity and the resulting polarization of carbon-fluorine bonds. Simultaneously, sterically-hindered N-heterocyclic carbenes (NHCs) have received major interest due to high stabilization of the reactive metal centers, which has paved the way for the synthesis of stable and reactive organometallic compounds with broad applications in main group chemistry, inorganic synthesis and transition-metal-catalysis. Herein, we report the first class of sterically-hindered, fluorinated N-heterocyclic carbenes. These ligands feature variable fluorine substitution at the N-aromatic wingtip, permitting to rationally vary steric and electronic characteristics of the carbene center imparted by the fluorine atom. An efficient, one-pot synthesis of fluorinated IPr*F ligands is presented, enabling broad access of academic and industrial researchers to the fluorinated ligands. The evaluation of steric, electron-donating and π-accepting properties as well as coordination chemistry to Au(I), Rh(I) and Se is presented. Considering the unique properties of carbon-fluorine bonds, we anticipate that this novel class of fluorinated carbene ligands will find widespread application in stabilizing reactive metal centers.

[(1,2,5,6-η)-Cyclo-octa-1,5-diene](1-ethyl-4-isobutyl-1,2,4-triazol-5-yl-idene)(tri-phenyl-phosphane)rhodium(I) tetra-fluorido-borate.

A new, cationic N-heterocyclic carbene RhI complex with a tetra-fluorido-borate counter-anion, [Rh(C8H12)(C8H15N3)(C18H15P)]BF4, has been synthesized and structurally characterized. There are two independent ion pairs in the asymmetric unit. Each complex cation exhibits a distorted square-planar conformation around the RhI atom. Bond lengths and bond angles are as expected for an Rh-NHC complex. There are several close, non-standard C-H⋯F hydrogen-bonding inter-actions between the ions. One of the tetra-fluorido-borate anions shows statistical disorder of the F atoms.

Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties.

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer.

Dye induced luminescence properties of gold(I) complexes with near unity quantum efficiency.

To study the effect of a dye on the photoluminescence (PL) properties of metal complexes, a series of gold(I) complexes were synthesized, containing a 7-amino-4-methylcoumarin luminophore. The complexes are comprised of a coumarin moiety featuring different ancillary ligands, specifically N-heterocyclic carbenes, triphenylphosphine, and diphenyl-2-pyridylphosphine. The synthesized gold(I) complexes are luminescent both in solution and the solid state at room temperature and 77 K. Complexes of different nuclearity, i.e., mono-, di- and trinuclear compounds were synthesized. A clear trend between the nuclearity and the quantum yields can be seen. The coumarin dye not only improves the PL properties, but also enhances the luminescence of trinuclear clusters, which are otherwise known to be weak emitters in solution. The optical absorption properties were investigated in detail by quantum chemical calculations.

Chlorido-[(1,2,5,6-η)-cyclo-octa-1,5-diene](1-ethyl-4-isobutyl-1,2,4-triazol-5-yl-idene)rhodium(I).

A new neutral triazole-based N-heterocyclic carbene rhodium(I) complex [RhCl(C8H12)(C8H15N3)], has been synthesized and structurally characterized. The complex crystallizes with two mol-ecules in the asymmetric unit. The central rhodium(I) atom has a distorted square-planar coordination environment, formed by a cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene (NHC) ligand, and a chlorido ligand. The bond lengths are unexceptional. A weak inter-molecular non-standard hydrogen-bonding inter-action exists between the chlorido and NHC ligands.

N-Heteroocyclic Carbenes and N-Heterocycles as Synthetic Reagents and Building Blocks.

N-Heterocyclic carbenes (NHCs) have become important tools in modern synthetic chemistry due to their versatility as organocatalysts and ligands in organometallic complexes. Since their first isolation and characterization, NHCs have demonstrated significant utility in various catalytic processes, offering advantages such as strong σ-electron donation and the ability to stabilize reactive intermediates. However, beyond their well-documented roles in catalysis, the potential of NHCs as stoichiometric reagents and synthetic building blocks remains an underexplored yet promising area. This Mini-review aims to shed light on these lesser-known applications of NHCs and their N-heterocyclic precursors or derivatives in organic synthesis. Furthermore, we discuss how the unique electronic and steric properties of NHCs can be harnessed to develop new synthetic methodologies or construct interesting organic frameworks. By highlighting these emerging uses, we hope to encourage further research into the non-catalytic applications of NHCs, broadening their scope and impact in synthetic chemistry.

Stereoselective Hydroxyallylation of Cyclopropenes with Cyclopropanols via NHC Catalysis of Transient Organozinc Species.

A stereoselective hydroxyallylation reaction of cyclopropenes with cyclopropanols is achieved under zinc-mediated conditions, affording densely functionalized cyclopropanes with excellent diastereocontrol over three contiguous stereocenters within and outside the cyclopropane ring. A racemic variant of the reaction is synergistically promoted by catalytic N-heterocyclic carbene (NHC) and organic base, whereas chiral amino alcohol-derived bifunctional NHC enables a catalytic enantioselective variant. The reaction likely involves the generation of enolized zinc homoenolate via ring-opening of zinc cyclopropoxide and enolization of the resulting homoenolate, followed by its addition to the cyclopropene as a prochiral allylzinc nucleophile. Our mechanistic investigations highlighted the transient nature of enolized homoenolate, which, once generated from thermodynamically predominant cyclopropoxide, immediately proceeds to allylzincation with cyclopropene. The NHC not only promotes the rate-determining generation of enolized homoenolate but also engages in the allylzincation process. The resulting cyclopropylzinc species undergoes partial in situ protonation while partially remaining intact, thereby leaving an opportunity for trapping with an external electrophile.

Photoinduced Single Electron Reduction of the 4-O-5 Linkage in Lignin Models for C-P Coupling Catalyzed by Bifunctional N-Heterocyclic Carbenes.

Catalytic activation of Caryl-O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4-O-5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light-induced bifunctional N-heterocyclic carbene (NHC)-catalyzed one-electron reduction of diaryl ether 4-O-5 linkage models for the synthesis of trivalent phosphines. The H-bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one-electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model.

Metal complexes of backbone-halogenated imidazol-2-ylidenes.

In this manuscript, literature reports on mono- and di-halogen (F, Cl, Br, and I) substituted at positions 4 or/and 4,5 imidazol-2-ylidene (NHC) metal complexes are discussed: particularly, their structural diversity with various metals (groups 6-13), important physicochemical properties, catalytic and medicinal/biological applications are reviewed. To our knowledge, there are no literature reports on group 4 and 5 metal complexes with this type of NHC ligands. Halogenated imidazol-2-ylidene metal complexes deserve special attention because halogens are the classic electron donating groups (mesomerically) in conjugated aromatic/heteroaromatic ring systems, but electron withdrawing inductively. However, they exhibit a significant electron withdrawing inductive effect, thus providing unique electronic properties. This is important for fine tuning of σ-donor abilities of the "carbenic" carbon of imidazol-2-ylidenes, which directly affect catalytic performance of their metal complexes. Other applications, advantages, and disadvantages of halogenated vs. unsubstituted imidazol-2-ylidene metal complexes are critically analyzed and summarized in this review.

Non-Kekulé meta-Quinodimethane Singlet Diradicals Based on Classical N-Heterocyclic Carbenes.

Diradicals based on a meta-quinodimethane (m-QDM) scaffold generally have a triplet ground state and are rather scarce. Herein, m-QDM-based non-Kekulé diradicals [3,3'-(NHC)2BP] (3-NHC) (NHC = SIPr = C{N(Dipp)CH2}2; IPr = C{N(Dipp)CH}2, Me-IPr = C{N(Dipp)CMe}2; Dipp = 2,6-iPr2C6H3; BP = 1,1'-C6H3C6H3) featuring N-heterocyclic carbene (NHC) pendants are reported as crystalline solids. The EPR spectra of 3-NHC show both allowed (Dms = 1) and forbidden (Dms = 2; 'half-field') transitions characteristic for triplet diradicals. Variable temperature EPR studies however reveal a singlet ground state for 3-SIPr. Consistent with the EPR spectra, calculations predict a remarkably small (open-shell) singlet-triplet energy gap (ΔEST ≤ 0.26 kcal/mol) for the 3-NHC compounds. The calculated singlet diradical character for the ground states of the 3-NHC compounds amounts to ~99%.

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.

Carbene-coated metal nanoparticles for in vivo applications.

N-Heterocyclic carbenes (NHC) are well-recognized ligands of choice for preparing robust transition metal species. However, their use for fabrication of biomedically relevant nanoparticles has been limited to the synthesis of non-targeted particles showing increased tolerance to different aqueous coagulants. In this work, the first example of carbene-coated metal nanoparticles suitable for in vivo applications is presented. Directed design of a novel biscarbene NHC ligand allowed to prepare the first magnetite/gold (Fe3O4@AuNP@NHC) nanostructures and carbene gold (AuNP@NHC) nanoparticles with significant stability in aqueous solutions and enhanced ability to form bioconjugates. Furthermore, these nanoparticles exhibit an extraordinary property for inorganic nanoparticles: they can endure several additive-free air drying/redispersion cycles without deterioration of their colloidal behavior. Bioconjugated AuNP@NHC and multimodal Fe3O4@AuNP@NHC demonstrated a successful performance in three distinct applications: lateral flow tests, specific cancer cell targeting, and bioimaging. Thus, the results show the notable advantages of the N-heterocyclic carbene coating of inorganic nanoparticles and their utility for complex biomedical applications.

Synthesis of a Metalla[2]catenane, Metallarectangles and Polynuclear Assemblies from Di(N-Heterocyclic Carbene) Ligands.

The 2,7-fluorenone-linked bis(6-imidazo[1,5-a]pyridinium) salt H2-1(PF6)2 reacts with Ag2O in CH3CN to yield the [2]catenane [Ag4(1)4](PF6)4. The [2]catenane rearranges in DMF to yield two metallamacrocycles [Ag2(1)2](PF6)2. 2,7-Fluorenone-bridged bis-(imidazolium) salts H2-L(PF6)2 (L=2 a, 2 b) react with Ag2O in CH3CN to yield metallamacrocycles [Ag2(L)2](PF6)2 with interplanar distances between the fluorenone rings too small for [2]catenane formation. Intra- and intermolecular π⋅⋅⋅π interactions between the fluorenone groups were observed by X-ray crystallography. The strongly kinked 2,7-fluorenone bridged bis(5-imidazo[1,5-a]pyridinium) salt H2-4(PF6)2 reacts with Ag2O to yield [Ag2(4)(CN)](PF6), while the tetranuclear assembly [Ag4(4)2(CO3)](PF6)2 was obtained in the presence of K2CO3.

(4-Butyl-1-ethyl-1,2,4-triazol-5-yl-idene)[(1,2,5,6-η)-cyclo-octa-1,5-diene](tri-phenyl-phosphane)iridium(I) tetra-fluorido-borate.

The title compound, [Ir(C8H12)(C8H15N3)(C18H15P)]BF4, a new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetra-fluorido-borate counter-anion, crystallizes with two cations and two anions in the asymmetric unit of space group Pc. The Ir centers of the cations have distorted square-planar conformations, formed by a bidentate (η2 + η2) cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene and a tri-phenyl-phosphane ligand with the NHC carbon atom and P atom being cis. In the extended structure, non-classical C-H⋯F hydrogen bonds, one of which is notably short (H⋯F = 2.21 Å), link the cations and anions. The carbon atoms of one of the COD ligands are disordered over adjacent sites in a 0.62:0.38 ratio.

Catalytic Upgrading of Acetaldehyde to Acetoin Using a Supported N-Heterocyclic Carbene Catalyst.

We report the catalytic synthesis of 3-hydroxy-2-butanon (acetoin) from acetaldehyde as a key step in the synthesis of C4-molecules from ethanol. Facile C-C bond formation at the α-carbon of the C2 building block is achieved using an N-heterocyclic carbene (NHC) catalyst. The immobilization of the catalyst on a Merrifield's peptide resin and its spectroscopic characterisation using solid-state Nuclear Magnetic Resonance (NMR) is described herein. The immobilization of the NHC catalyst allows for process intensification steps and the reported catalytic system was subjected to batch recycling as well as continuous flow experiments. The robustness of the catalytic system was shown over a maximum of 10 h time-on-stream. Overall, high selectivity S>90 % was observed. The observed deactivation of the catalyst with increasing time-on-stream is explained by ex-situ 1H solution-state, as well as 13C and 15N solid-state NMR spectra allowing us to develop a deeper understanding of the underlying decomposition mechanism of the catalyst.

Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Gold Nanoparticles with N-Heterocyclic Carbene/Triphenylamine Surface Ligands: Stable and Electrochromically Active Hybrid Materials for Optoelectronics.

Organic-hybrid particle-based materials are increasingly important in (opto)electronics, sensing, and catalysis due to their printability and stretchability as well as their potential for unique synergistic functional effects. However, these functional properties are often limited due to poor electronic coupling between the organic shell and the nanoparticle. N-heterocyclic carbenes (NHCs) belong to the most promising anchors to achieve electronic delocalization across the interface, as they form robust and highly conductive bonds with metals and offer a plethora of functionalization possibilities. Despite the outstanding potential of the conductive NHC-metal bond, synthetic challenges have so far limited its application to the improvement of colloidal stabilities, disregarding the potential of the conductive anchor. Here, NHC anchors are used to modify redox-active gold nanoparticles (AuNPs) with conjugated triphenylamines (TPA). The resulting AuNPs exhibit excellent thermal and redox stability benefiting from the robust NHC-gold bond. As electrochromic materials, the hybrid materials show pronounced color changes from red to dark green, a highly stable cycling stability (1000 cycles), and a fast response speed (5.6 s/2.1 s). Furthermore, TPA-NHC@AuNP exhibits an ionization potential of 5.3 eV and a distinct out-of-plane conductivity, making them a promising candidate for application as hole transport layers in optoelectronic devices.

Synthesis and Medicinal Applications of N-Heterocyclic Carbene Complexes Based on Caffeine and Other Xanthines.

Xanthines are purine derivatives predominantly found in plants. These include compounds such as caffeine, theophylline, and theobromine and exhibit a variety of pharmacological properties, demonstrating efficacy in treating neurodegenerative disorders, respiratory dysfunctions, and also cancer. The versatile attributes of these materials render them privileged scaffolds for the development of compounds for various biological applications. Xanthines are N-heterocyclic carbene precursors that combine a pyrimidine and an imidazole ring. Owing to their biological relevance, xanthines have been employed as N-heterocyclic carbenes in the development of metallodrugs for anticancer and antimicrobial purposes. In this conceptual review, we examine key examples of N-heterocyclic carbene complexes derived from caffeine and other xanthines, elucidating their synthetic methods and describing their pertinent medicinal applications.

Impact of Backbone Substitution on Organocatalytic Activity of Sterically Encumbered NHC in Benzoin Condensation.

In this study, we provide a theoretical explanation for the experimentally observed decrease in the organocatalytic activity of N-aryl imidazolylidenes methylated at the C4/5-H positions in the benzoin condensation of aromatic aldehydes. A comparative quantum chemical study of energy profiles for the NHC-mediated benzoin condensation of furfural has revealed a high energy barrier to the formation of the IPrMe-based furanic Breslow intermediate that can be attributed to the negative steric interactions between the imidazole backbone methyl groups and N-aryl substituents.

L→S Coordination Complexes Containing Benzothiazol-2-ylidene Ligand: Quantum Chemical Analysis and Synthesis.

(NHC)→E coordination interactions were known where NHC is an N-heterocyclic carbene, and E is a main group element (B, C, N, Si, P). Recently, it was suggested that compounds with (NHC)→S coordination chemistry are also possible. This work reports quantum chemical analysis and synthesis of (NHC)→S-R(+) complexes in which benzothiazol-2-ylidene acts as a ligand. A Density functional study established that (NHC)→S interaction can best be described as a coordination interaction. Synthetic efforts were made, initially, to generate divalent sulfur compounds containing benzothiazole substituents. N-alkylation of the heterocyclic ring in these sulfides using methyl triflate led to the generation of the desired products with (NHC)→S coordination chemistry, which involves the in situ generation of NHC ring ligands. The observed changes in the 13C NMR spectra, before and after methylation, confirmed the change in the electronic character of the C-S bond from a covalent character to a coordination character.