Unsaturated N-heterocyclic Carbene Research Articles

Frustrated Lewis Pair-Type Reactivity of Intermolecular Rare-Earth Aryloxide and N-Heterocyclic Carbene/Olefin Combinations.

This work reports the cooperative reactivity of rare-earth aryloxide complexes with N-heterocyclic carbene (NHC) or N-heterocyclic olefin (NHO), showcasing their synergistic effect on the activation of H2 and diverse organic substrates. Reactions of RE(OAr)3 (RE=La, Sm, and Y; Ar=2,6-tBu2-C6H3) with unsaturated NHC ItBu (:C[N(R)CH]2, R=tBu) isolated abnormally bound RE metal NHC complexes RE/aNHC. In contrast, no metal-NHO adducts were formed when RE(OAr)3 were treated with NHO (R2C=C[N(R)C(R)]2, R=CH3). Both RE/aNHC and RE/NHO Lewis pairs enabled cooperative H2 activation. Furthermore, RE(OAr)3 were found to catalyze the hydrogenation of the exocyclic C=C double bond of NHO under mild conditions. Moreover, treatment of the La/aNHC complex with benzaldehyde produced a La/C4 1,2-addition product. The La/NHO Lewis pair could react with (trimethylsilyl)diazomethane and α, β-conjugated imine, affording an isocyanotrimethylsilyl lanthanum amide complex and a La/C 1,4-addition product, respectively.

Continuous Flow Synthesis of Sulfur‐ and Selenium−NHC Compounds (NHC=N‐Heterocyclic Carbene)

AbstractThe first continuous flow syntheses of sulfur‐ and selenium−NHC (NHC=N‐heterocyclic carbene) adducts in unprecedented short reaction times and high yields are reported. The importance of these species in coordination chemistry or as efficient tools for determining the π‐acceptor character of NHC ligands make any improvement in their synthesis a worthy goal. Thiourea derivatives bearing both saturated and unsaturated NHCs were obtained using NEt3 as a weak base (homogeneous setup) in conjunction with a bed of elemental sulfur (S8). The synthetic route proving optimal for selenoureas involves the use of a simple Se/K2CO3 heterogeneous microreactor design.

Catalytic Method for the Synthesis of Deuterium-Labeled N-Heterocyclic Carbenes Enabled by a Coordinatively Unsaturated Ruthenium N-Heterocyclic Carbene Catalyst.

The wide usage of N-heterocyclic carbenes (NHCs) has raised the quest for their deuterated molecules. Effective synthesis method to obtain them, however, has remained elusive. We present here a catalytic method for the preparation of deuterated NHCs, namely, the catalytic hydrogen-deuterium exchange reaction between NHCs and deuterated benzene using a coordinatively unsaturated Ru NHC catalyst. The catalytic system enables selective deuteration of the C(sp3)-H bonds of the alkyl groups on N-substituents, as well as the sterically nonhindered C(sp2)-H bonds of NHCs as demonstrated by the preparation of 16 deuterium-labeled NHCs that have a deuteration ratio on specified sites higher than 90%. The gram-scale synthesis of deuterated IMes indicated the applicability of this catalytic method. Mechanistic studies revealed that the high regio-selectivity toward those C(sp3)-H bonds on NHCs originates from the regio-selectivity of cyclometalation reactions of coordinatively unsaturated Ru NHC species.

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

Probing the aromaticity of unsaturated N-heterocyclic carbenes and their heavy analogues with the EDDB criterion

Probing the aromaticity of unsaturated N-heterocyclic carbenes and their heavy analogues with the EDDB criterion

Nature of Metal-Drug Bond in Some Antitumor Active Complexes of Coinage Metal Ions.

N-Heterocyclic carbene and phosphine can be labeled as solid σ-donor ligands and can contribute to stable complexes. In addition, the constructed complex can accommodate a wide variety of applications, such as pharmaceutical products. In the light of this, a theoretical analysis was carried out on the existence of metal–drug interactions of group 11 metal ions in coordination with symmetrical unsaturated N-heterocyclic carbenes [NHC(R)(R′)] and monodentate phosphine (PR3). The R substitutes on N atoms in NHC and phosphines are identical, and R′ substitutes are located on two noncarbenic carbon atoms (C4 and C5) in the heterocycle complexes. All complexes are in general formula, [Tgt → ML] {where M = Cu(I), Ag(I), Au(I), Tgt = 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranoside, L= [NHC(R)(R′)], and PR3; R = F, Cl, Br, H, CH3, C2H5, SiH3, 2,6-diisopropylphenyl; R′ = H and Ph} at the PBE-D3/def2-TZVP level of theory. Findings show greater tolerance for the release of drugs in the presence of Ag(I) metal ions than the other metal ions studied here. Applying natural bond orbital (NBO), atoms in molecules (AIMs), energy decomposition analysis (EDA), and extended transition-state natural orbital for chemical valence (ETS-NOCV) analysis have been researched in order to ascertain the nature of M ← S and M ← C (M ← P) bonds in the complexes. Results have shown that σ donation from S to M atoms in [Tgt → MPR3] complexes is better and the π acceptor is weaker than the corresponding [Tgt → MNHC(R)(R′)] complexes.

Unsaturated and Benzannulated N-Heterocyclic Carbene Complexes of Titanium and Hafnium: Impact on Catalysts Structure and Performance in Copolymerization of Cyclohexene Oxide with CO2.

Tridentate, bis-phenolate N-heterocyclic carbenes (NHCs) are among the ligands giving the most selective and active group 4-based catalysts for the copolymerization of cyclohexene oxide (CHO) with CO2. In particular, ligands based on imidazolidin-2-ylidene (saturated NHC) moieties have given catalysts which exclusively form polycarbonate in moderate-to-high yields even under low CO2 pressure and at low copolymerization temperatures. Here, to evaluate the influence of the NHC moiety on the molecular structure of the catalyst and its performance in copolymerization, we extend this chemistry by synthesizing and characterizing titanium complexes bearing tridentate bis-phenolate imidazol-2-ylidene (unsaturated NHC) and benzimidazol-2-ylidene (benzannulated NHC) ligands. The electronic properties of the ligands and the nature of their bonds to titanium are studied using density functional theory (DFT) and natural bond orbital (NBO) analysis. The metal–NHC bond distances and bond strengths are governed by ligand-to-metal σ- and π-donation, whereas back-donation directly from the metal to the NHC ligand seems to be less important. The NHC π-acceptor orbitals are still involved in bonding, as they interact with THF and isopropoxide oxygen lone-pair donor orbitals. The new complexes are, when combined with [PPN]Cl co-catalyst, selective in polycarbonate formation. The highest activity, albeit lower than that of the previously reported Ti catalysts based on saturated NHC, was obtained with the benzannulated NHC-Ti catalyst. Attempts to synthesize unsaturated and benzannulated NHC analogues based on Hf invariably led, as in earlier work with Zr, to a mixture of products that include zwitterionic and homoleptic complexes. However, the benzannulated NHC-Hf complexes were obtained as the major products, allowing for isolation. Although these complexes selectively form polycarbonate, their catalytic performance is inferior to that of analogues based on saturated NHC.

New NHC- silver and gold complexes active in A3-coupling (aldehyde-alkyne-amine) reaction

Silver and gold complexes bearing unsaturated N-heterocyclic carbene ligands, with unsymmetrical N-substituents and hydrogen or chlorine on backbone, have been synthetized and their efficiency tested in A3-coupling (aldehyde–alkyne–amine) reactions. Gold complexes showed higher activity than corresponding silver ones, even if the significant role of the backbone substituents should not be neglected. Indeed, complexes with chlorine substituted backbone were more efficient than hydrogen analogous. According to DFT calculations, electronic differences among complexes are able rationalize the different catalytic behavior, whereas steric properties play a minor part.

Ru-Based Catechothiolate Complexes Bearing an Unsaturated NHC Ligand: Effective Cross-Metathesis Catalysts for Synthesis of ( Z)-α,β-Unsaturated Esters, Carboxylic Acids, and Primary, Secondary, and Weinreb Amides.

Despite notable progress, olefin metathesis methods for preparation of ( Z)-α,β-unsaturated carbonyl compounds, applicable to the synthesis of a large variety of bioactive molecules, remain scarce. Especially desirable are transformations that can be promoted by ruthenium-based catalysts, as such entities would allow direct access to carboxylic esters and amides, or acids (in contrast to molybdenum- or tungsten-based alkylidenes). Here, we detail how, based on the mechanistic insight obtained through computational and experimental studies, a readily accessible ruthenium catechothiolate complex was found that may be used to generate many α,β-unsaturated carbonyl compounds in up to 81% yield and ≥98:2 Z/ E ratio. We show that through the use of a complex bearing an unsaturated N-heterocyclic carbene (NHC) ligand, for the first time, products derived from the more electron-deficient esters, acids, and Weinreb amides (vs primary or secondary amides) can be synthesized efficiently and with high stereochemical control. The importance of the new advance to synthesis of bioactive compounds is illustrated through two representative applications: an eight-step, 15% overall yield, and completely Z-selective route leading to an intermediate that may be used in synthesis of stagonolide E (vs 11 steps, 4% overall yield and 91% Z, previously), and a five-step, 25% overall yield sequence to access a precursor to dihydrocompactin (vs 13 steps and 5% overall yield, formerly).

Activation of olefin metathesis complexes containing unsymmetrical unsaturated N-heterocyclic carbenes by copper and gold transmetalation.

The activation of ruthenium-indenylidene complexes containing two unsymmetrical unsaturated N-heterocyclic carbenes (u2-NHCs) by a transmetalation process is reported. The use of copper(i) or gold(i) chlorides promotes the rapid trapping of one NHC ligand, which releases the catalytically active Ru-species. Impressive initiation rates with full-conversions are observed within one minute. This practical protocol demonstrates excellent catalytic performances in various ring-closing metathesis (RCM) and self-metathesis (SM) reactions.

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

Coordination behavior of bis-phenolate saturated and unsaturated N-heterocyclic carbene ligands to zirconium: reactivity and activity in the copolymerization of cyclohexene oxide with CO2.

Tetravalent zirconium complexes supported by tridentate bis-phenolate imidazolidin-2-ylidene (L1), imidazol-2-ylidene (L2) and benzimidazol-2-ylidene (L3) NHC ligands were synthesized and evaluated as precursors for the copolymerization of cyclohexene oxide (CHO) with CO2. While the reactivity of the imidazolidinium [H3L1] chloride salt with Zr(OiPr)4(HOiPr), and subsequent ligand exchanges with either (CH3)3SiCl or LiOiPr lead to a series of heteroleptic compounds (κ3-O,C,O-L1)Zr(X)2(THF) (X = Cl, OiPr), both imidazolium [H3L2] and benzimidazolium [H3L3] chloride salts give a mixture of homoleptic (κ3-O,C,O-NHC)2Zr and zwitterionic (κ2-O,O-HL)ZrCl2(OiPr) compounds along with traces or the absence of the heteroleptic intermediate (κ3-O,C,O-NHC)Zr(Cl)(OiPr)(THF). Such dissimilar reactivity between the unsaturated and saturated NHC ligands is predominantly ascribed to the increased acidity of azolium salts along with the π-donor strength of the Ccarbene in L2 and L3-Zr moieties. The reactivity with the more acidic azolium salts (H3L2/3) and the destabilized Zr-Xtrans to NHCcarbene bond results in a significant increase in the amount of homoleptic compounds generating HCl. The released HCl reacts preferentially with the heteroleptic intermediates having non-planar NHC ligands (i.e. L2/3) promoting the formation of zwitterionic complexes. The in situ deprotonation of the isolated zwitterionic (κ2-O,O-HL3)ZrCl2(OiPr) compound by using Ag2O gives the homoleptic complex as the major component along with a bimetallic hydroxo-bridged [(κ3-O,C,O-L3)Zr(μ-OH)(OiPr)]2 compound. Of particular interest is that only the heteroleptic NHC-Zr(iv) complexes were identified to be active and highly selective towards the copolymerization of CHO with CO2 independently of the co-catalysts used (both anionic and neutral) under mild conditions (PCO2 < 1 bar, T = 60 °C), and gave atactic and completely alternating copolymers in a controlled manner (Mw/Mn ≈ 1.3-1.8). In contrast, the isolated homoleptic, zwitterionic and bimetallic zirconium species were found to be inactive under similar reaction conditions. Although the activity found for NHC-Zr(iv) complexes is nearly of the same order of magnitude as that of the NHC-Ti(iv) analogues, these results are the first examples of tetravalent zirconium complexes achieving high selectivity (99% in PCHC) in the catalyzed copolymerization of CHO with CO2.

Experimental and theoretical investigations on the high-electron donor character of pyrido-annelated N-heterocyclic carbenes.

Rh(CO)2Cl(NHC) complexes of dipyrido-annelated N-heterocyclic carbenes were prepared. From the C–H coupling constant of the respective imidazolium salts and the N–C–N angle of the N-heterocyclic carbene (NHC), a weaker σ-donor character than that of typical unsaturated NHCs is expected. However, the IR stretching frequencies of their Rh(CO)2Cl complexes suggest an electron-donor character even stronger than that of saturated NHCs. We ascribe this to the extremely weak π-acceptor character of the dipyrido-annelated NHCs caused by the conjugated 14 πe− system that thus allows for an enhanced Rh–CO backbonding. This extremely low π-acceptor ability is also corroborated by the 77Se NMR chemical shift of −55.8 ppm for the respective selenourea, the lowest value ever measured for imidazole derived selenoureas. DFT-calculations of the free carbene confirm the low σ-donor character by the fact that the σ-orbital of the carbene is the HOMO−1 that lies 0.58 eV below the HOMO which is located at the π-system. Natural population analysis reveals the lowest occupation of the pπ-orbital for the saturated carbene carbon atom and the highest for the pyrido-annelated carbene. Going from the free carbene to the Rh(CO)2Cl(NHC) complexes, the increase in occupancy of the complete π-system of the carbene ligand upon coordination is lowest for the pyrido-annelated carbene and highest for the saturated carbene.

Cationic bis-N-heterocyclic carbene (NHC) ruthenium complex: structure and application as latent catalyst in olefin metathesis.

An unexpected cationic bis-N-heterocyclic carbene (NHC) benzylidene ether based ruthenium complex (2 a) was prepared through the double incorporation of an unsymmetrical unsaturated N-heterocyclic carbene (U2 -NHC) ligand that bore an N-substituted cyclododecyl side chain. The isolation and full characterization (including X-ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring-closing metathesis, which could be "switched on" under acidic conditions.

Chiral PEPPSI Complexes: Synthesis, Characterization, and Application in Asymmetric Suzuki–Miyaura Coupling Reactions

PEPPSI complexes incorporating chiral N-heterocyclic carbene (NHC) ligands based on 2,2-dimethyl-1-(o-substituted aryl)propan-1-amines were synthesized. Two complexes, with one saturated and one unsaturated NHC ligand, were structurally characterized. The chiral PEPPSI complexes were used in asymmetric Suzuki–Miyaura reactions, giving atropisomeric biaryl products in modest to good enantiomeric ratios.

Multicomponent Synthesis of Unsymmetrical Unsaturated N‐Heterocyclic Carbene Precursors and Their Related Transition‐Metal Complexes

A low-cost, modular, and easily scalable multicomponent procedure affording access in good yields and excellent selectivity (up to 93%) to a wide range of (a)chiral unsymmetrical 1-aryl-3-cycloalkyl-imidazolium salts is disclosed. Electronic and steric properties of the corresponding unsymmetrical unsaturated N-heterocyclic carbene (U2-NHC) ligands were evaluated and evidenced strong electron donor ability, high steric discrimination, and modular steric demand.

Unsaturated NHC Complexes Immobilized by the Backbone: Synthesis and Application

AbstractThe synthesis and an exemplary catalytic application of a SBA‐15‐supported rhodium–N‐heterocyclic carbene (NHC) complex is reported. In contrast to the conventional method of immobilization of unsaturated NHC complexes, the rhodium–NHC compound described here is connected to the SBA‐15 surface by a linker originating from the backbone of the unsaturated NHC ligand. The unique characteristics of the new immobilization mode enable the supported NHC complexes to maintain two unchanged “wing‐tip” ligands. This method of immobilization of unsaturated NHC complexes provides a new way to maintain the original configuration of homogeneous NHC complexes in the heterogenized catalytic system. The immobilized rhodium–NHC catalyst is used in a hydrogenation reaction with styrene as substrate.

Alkali-metal-mediated zincation (AMMZn) meets N-heterocyclic carbene (NHC) chemistry: Zn–H exchange reactions and structural authentication of a dinuclear Au(i) complex with a NHC anion

Merging two evolving areas in synthesis, namely cooperative bimetallics and N-heterocyclic carbenes (NHCs), this study reports the isolation of the first intermediates of alkali-metal-mediated zincation (AMMZn) of a free NHC and a Zn–NHC complex using sodium zincate [(TMEDA)NaZn(TMP)(tBu)2] (1) as a metallating reagent. The structural authentication of (THF)3Na[:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}] (2) and [Na(THF)6]+[tBu2Zn:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}]− (4), resulting from the reactions of 1 with unsaturated free NHC IPr (IPr = 1,3-bis(2,6-di-isopropylphenylimidazole-2-ylidene) and NHC complex ZntBu2IPr (3) respectively demonstrates that in both cases, this mixed-metal approach can easily facilitate the selective C4 zincation of the unsaturated backbone of the NHC ligand. Furthermore, the generation of anionic NHC fragments enables dual coordination through their normal (C2) and abnormal (C4) positions to the bimetallic system, stabilising the kinetic AMMZn intermediates which normally go undetected and provides new mechanistic insights in to how these mixed-metal reagents operate. In stark contrast to this bimetallic approach when NHC-complex 3 is reacted with a more conventional single-metal base such as tBuLi, the deprotonation of the coordinated carbene is inhibited, favouring instead, co-complexation to give NHC-stabilised [IPr·LiZntBu3] (5). Showing the potential of 2 to act as a transfer agent of its anionic NHC unit to transition metal complexes, this intermediate reacts with two molar equivalents of [ClAu(PPh3)] to afford the novel digold species [ClAu:C{[N(2,6-iPr2C6H3)]2CHCAu(PPh3)}] (6) resulting from an unprecedented double transmetallation reaction which involves the simultaneous exchange of both cationic (Na+) and neutral (ZntBu2) entities on the NHC framework.

Synthesis of Various Saturated and Unsaturated N‐Heterocyclic Carbene Precursors by Triflic Anhydride Mediated Intramolecular Cyclization

Closing the circle: A versatile and modular method yields various saturated and unsaturated N-heterocyclic carbene precursors from a Tf2O-mediated intramolecular cyclization reaction. A resultant sterically demanding oxazolium salt could be used not only as good intermediate for directly preparing N,N′-disubstituted imidazolium salts in one step, but also as a precursor of sterically demanding oxazol-2-ylidene. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

When Does Carbonylation of Carbenes Yield Ketenes? A Theoretical Study with Implications for Synthesis

Quantum-chemical calculations using DFT and ab initio methods have been carried out for 32 carbenes RR'C which comprise different classes of compounds and the associated ketenes RR'C═C═O. The calculated singlet-triplet gaps ΔE(S-T) of the carbenes exhibit a very high correlation with the bond dissociation energies (BDEs) of the ketenes. An energy decomposition analysis of the RR'C-CO bond using the triplet states of the carbene and CO as interacting fragments supports the assignment of ΔE(S-T) as the dominant factor for the BDE but also shows that the specific interactions of the carbene may sometimes compensate for the S/T gap. The trend of the interaction energy ΔE(int) values is mainly determined by the Pauli repulsion between the carbene and CO. The stability of amino-substituted ketenes strongly depends on the destabilizing conjugation between the nitrogen lone-pair orbital and the ketene double bonds. There is a ketene structure of the unsaturated N-heterocyclic carbene parent compound NHC1 with CO as a local energy minimum on the potential-energy surface. However, the compound NHC1-CO is thermodynamically unstable toward dissociation. The saturated homologue NHC2-CO has only a very small bond dissociation energy of D(e) = 3.2 kcal/mol. The [3]ferrocenophane-type compound FeNHC-CO has a BDE of D(e) = 16.0 kcal/mol.