N-heterocyclic Carbene Ring Research Articles

Pd–PEPPSI-type expanded ring N-heterocyclic carbene complexes: synthesis, characterization, and catalytic activity in Suzuki–Miyaura cross coupling

ABSTRACT In this work, we synthesized a series of six unsymmetrical benzimidazolium salts 2 and their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)]. All the products were isolated in satisfactory yields (75-85%). The synthesis of these novel palladium PEPPSI complexes involved in reacting NHC precursors with PdCl2 in pyridine at 60°C in the presence of excess K2CO3. The structures of all compounds have been characterized by 1H NMR, 13C NMR, HRMS and IR spectroscopy, as well as elemental analysis techniques, which support the proposed structures. The catalytic activity of the six complexes was assessed in the Suzuki-Miyaura cross-coupling of phenylboronic acid and aryl halides. The reactions required only a low catalyst loading (0.1 mol%) and were carried out under mild aerobic conditions in a green, water-based solvent mixture.

NHC Carbene-Metal Complex Ligand Binding Energies.

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

Subvalent group 13 molecules by carbene-induced hydrogen abstraction.

The N-Heterocyclic Carbene (NHC) alane and gallane adducts (NHC)·Cp*AlH2 (NHC = Me2ImMe5, iPr2ImMe6, Dipp2Im 7) and (NHC)·Cp*GaH2 (NHC = Me2ImMe8, iPr2ImMe9, Dipp2Im 10; R2Im = 1,3-di-organyl-imidazolin-2-ylidene; Dipp = 2,6 diisopropylphenyl; Me2ImMe = 1,3,4,5-tetra-methyl-imidazolin-2-ylidene; Cp* = C5Me5) were prepared either via the reaction of (AlH2Cp*)31 with the NHC or by the treatment of (NHC)·GaH2I (NHC = Me2ImMe2, iPr2ImMe3, Dipp2Im 4) with KCp*. The reaction of (AlH2Cp*)31 with the backbone saturated NHC Dipp2ImH led to NHC ring expansion instead with the formation of (RER-Dipp2ImHH2)AlCp* 12. Heating solutions of the gallium compounds 8-10 triggered reductive elimination of Cp*H and afforded Cp*GaI16. The reaction of the alane adduct (Me2ImMe)·Cp*AlH25 with cAACMe led to the insertion of cAACMe into the Al-H bond with the formation of the compound rac-(Me2ImMe)·AlHCp*(cAACMeH) rac-14. Heating a solution of rac-14 led to irreversible isomerisation with the formation of (Me2ImMe)·AlHCp*(cAACMeH) meso-14. The alane adducts (iPr2ImMe)·Cp*AlH26 and (Dipp2Im)·Cp*AlH27 react with cAACMe with the release of the NHC and formation of the exceptionally stable oxidative addition product (cAACMeH)AlHCp* 15. Reactions of the gallane adducts 8-10 with cAACMe led to reductive elimination of cAACMe-H2 and the formation of Cp*GaI16.

Ruthenium pincer complexes for light activated toxicity: Lipophilic groups enhance toxicity

Nine ruthenium CNC pincer complexes (1–9) were tested for anticancer activity in cell culture under both dark and light conditions. These complexes included varied CNC pincer ligands including OH, OMe, or Me substituents on the pyridyl ring and wingtip N-heterocyclic carbene (NHC) groups which varied as methyl (Me), phenyl (Ph), mesityl (Mes), and 2,6-diisopropylphenyl (Dipp). The supporting ligands included acetonitrile, Cl, and 2,2′-bipyridine (bpy) donors. The synthesis of complexes 8 and 9 is described herein and are fully characterized by spectroscopic (1H NMR, IR, UV–Vis, MS) and analytical techniques. Single crystal X-ray diffraction results are reported herein for 8 and 9. The other complexes (1–7) are reported elsewhere. The four most lipophilic ruthenium complexes (6, 7, 8, and 9) showed the best activity vs. MCF7 cancer cells with complexes 6 and 9 showing cytotoxicity and complex 7 and 8 showing light activated photocytotoxicity. The distribution of these compounds between octanol and water is reported as log(Do/w) values, and increasing log(Do/w) values correlate roughly with improved activity vs. cancer cells. Overall, lipophilic wingtip groups (e.g. Ph, Mes, Dipp) on the NHC ring and a lower cationic charge (1+ vs. 2+) appears to be beneficial for improved anticancer activity.

Gold(I) N-heterocyclic carbene precursors for focused electron beam-induced deposition.

Seven gold(I) N-heterocyclic carbene (NHC) complexes were synthesized, characterized, and identified as suitable precursors for focused electron beam-induced deposition (FEBID). Several variations on the core Au(NHC)X moiety were introduced, that is, variations of the NHC ring (imidazole or triazole), of the alkyl N-substituents (Me, Et, or iPr), and of the ancillary ligand X (Cl, Br, I, or CF3). The seven complexes were tested as FEBID precursors in an on-substrate custom setup. The effect of the substitutions on deposit composition and growth rate indicates that the most suitable organic ligand for the gold precursor is triazole-based, with the best deposit composition of 15 atom % gold, while the most suitable anionic ligand is the trifluoromethyl group, leading to a growth rate of 1 × 10−2 nm3/e−.

Functionalised N-Heterocyclic Carbene Ligands in Bimetallic Architectures.

N‐Heterocyclic carbenes (NHCs) have become immensely successful ligands in coordination chemistry and homogeneous catalysis due to their strong terminal σ‐donor properties. However, by targeting NHC ligands with additional functionalisation, a new area of NHC coordination chemistry has developed that has enabled NHCs to be used to build up bimetallic and multimetallic architectures. This minireview covers the development of functionalised NHC ligands that incorporate additional donor sites in order to coordinate two or more metal atoms. This can be through the N‐atom of the NHC ring, through a donor group attached to the N‐atom or the carbon backbone, coordination of the π‐bond or an annulated π‐donor on the backbone, or through direct metalation of the backbone.

Azobenzene Isomerization-Induced Photomodulation of Electronic Properties of N-Heterocyclic Carbenes.

Azobenzene-based protonated N-heterocyclic carbenes (NHCs), N,N'-bis(azobenzene)imidazolium chlorides (IAz-X⋅HCl; X=OMe, Br, H) were successfully synthesized and switching abilities of the attached azobenzene units along with the concomitant photoinduced generation of geometric isomers were studied. Upon irradiation with 365 nm UV light, a p-methoxy-azobenzene derivative get transformed from all-trans isomer to nearly all-cis isomer at the photostationary state. The extent of photomodulation of electronic properties in the NHC ring of the p-methoxy-azobenzene derivative is determined through the Tolman Electronic Parameter (TEP). Iridium complex, [(IAz-OMe)IrCl(CO)2 ] was synthesized and infrared spectra were recorded in dichloromethane solution as film in NaCl crystals and by drop-casting in an ATR crystal. Comparison in averaged carbonyl stretching frequency between all-trans isomer ( ) and all-cis isomer ( ) indicates a significant decrement of Δtt-cc av =2.7 cm-1 (film) and 3.8 cm-1 (ATR). Therefore, moderate to excellent enhancement of electron density (Δtt-cc TEP=2.3 cm-1 [film] and 3.2 cm-1 [ATR]) at the C-2 position of the NHC is achieved through trans→cis isomerization of the remotely placed azobenzene units. This fine phototuning of electron-donating ability at the catalytic center would pave the way to control NHC/NHC-metal catalyzed organic transformations through external stimuli.

New expanded-ring NHC platinum(0) complexes: Synthesis, structure and highly efficient diboration of terminal alkenes

The synthesis and structural characterization of a series of novel platinum(0) complexes were reported. A number of (NHC)Pt(dvtms) (dvtms = 1,3-divinyl-1,1,3,3-tetramethyldisiloxane) complexes were investigated in catalytic addition of B2Pin2 to terminal alkenes. The novel expanded ring N-heterocyclic carbene complex (7-Dipp)Pt(dvtms) showed highest performance, turnover numbers up to 3800 were achieved. The scope of the reaction was illustrated by 20 examples with a variety of alkyl, alkoxy, halogen, ester, ketone and acetal substituents.

A resorcinarene-based tetrabenzoimidazolylidene complex of rhodium.

A tetrabenzoimidazolium-resorcinarene cavitand was used for the preparation of a tetra-benzoimidazolylidene of rhodium, which is unprecedented in the field of poly-NHC metal complexes. Both the experimental and computational analyses of the molecule reveal a distorted vase conformation as the most stable one, although several non-interconverting conformational isomers due to the restricted rotation about the Rh-C(carbene) bond coexist in the product. There is a fluxional behaviour involving the vase-kite interconversion. The main interactions between the arms of the cavitand are mostly concentrated on the terminal organometallic fragments attached to NHC, along with those between -CH3 and a N-heterocyclic carbene ring from benzoimidazoles.

Synthesis, reactivity and preliminary biological activity of iron(0) complexes with cyclopentadienone and amino‐appended N‐heterocyclic carbene ligands

Neutral and cationic cyclopentadienone (CpO) N‐heterocyclic carbene (NHC) bis‐carbonyl iron(0) complexes bearing, appended to the NHC ligand, either a terminal amino group on the lateral chain, [Fe(η4‐CpO)(CO)2(κC‐NHC(CH2)nNH2)] with n = 2 (2a) and 3 (2b), or a cationic NMe3+ fragment, [Fe(η4‐CpO)(CO)2(κC‐NHC(CH2)2NMe3)](I) (3), were prepared and characterized in terms of their structure, stability and reactivity. The photochemical properties of 2a and 2b were examined both in organic solvents and in water, revealing the photoactivated release of one CO ligand followed by the formation of the chelated complex [Fe(η4‐CpO)(CO)(κ2C,N‐NHC(CH2)2NH2)] (4), whose molecular structure was confirmed by single crystal X‐ray diffraction studies. This metallacyclization occurs only in the case of 2a, with the ethylene spacer between NHC ring and NH2 group in the lateral chain, allowing the formation of a stable 6‐membered ring. On the other hand, 2b undergoes decomposition upon irradiation. The reactivity in aqueous solutions revealed the chemical speciation of the complexes at different pH and especially under physiological conditions (phosphate buffer solution at pH 7.4 and 37 °C). The lack of data on the biological properties of iron(0) complexes prompted us to preliminarily investigate their cytotoxicity against model cancer cells (AsPC‐1 and HPAF‐II), along with a determination of their lipophilicity.

EPR and Preparative Studies of 5- endo Cyclizations of Radicals Derived from Alkenyl NHC-Boranes Bearing tert-Butyl Ester Substituents.

Radical H atom abstraction from a set of N-heterocyclic carbene (NHC) complexes of alkenylboranes bearing two tert-butyl ester substituents was studied by EPR spectroscopy. The initial boraallyl radical intermediates rapidly ring closed onto the O atoms of their distal ester groups in 5- endo mode to yield 1,2-oxaborole radicals. Unexpectedly, two structural varieties of these radicals were identified from their EPR spectra. These proved to be two stable rotamers, in which the carbonyl group of the tert-butyl ester was oriented toward and away from the NHC ring. These rotamers were akin to the s- trans and s- cis rotamers of α,β-unsaturated carbonyl compounds. Their stability was attributed to the quasi-allylic interaction of their unpaired electrons with the carbonyl units of their adjacent ester groups. EPR spectroscopic evidence for two rotamers of the analogous methyl ester containing NHC-oxaborole radicals was also obtained. An improved synthetic procedure for preparing rare NHC-boralactones was developed involving treatment of the alkenyl NHC-boranes with AIBN and tert-dodecanethiol.

Planar-Chiral Ferrocene-Based N-Heterocyclic Carbene Ligands.

In the last few decades, N-heterocyclic carbene (NHC) ligands, characterized by attractive features, have increased their presence in transition-metal catalysis. However, chiral NHC ligands still require further design enhancement to realize far more exciting synthetic applications. This review documents advances in chiral NHC ligands, focusing on planar-chiral ferrocene-based NHCs. As the basic shape of most classes of NHC rings is planar, it seems rational to employ a planar-chiral element in the design of chiral NHC ligands.

Copper-NHC-Mediated Semihydrogenation and Hydroboration of Alkynes: Enhanced Catalytic Activity Using Ring-Expanded Carbenes

A series of two-coordinate copper tert-butoxide complexes bearing five-, six-, and seven-membered ring N-heterocyclic carbenes, prepared by protonolysis of (NHC)CuMes with tBuOH, have been used as catalytic precursors in the semihydrogenation of alkynes with silanes/tBuOH and the hydroboration of alkynes with HBPin. Both processes proceed with high regioselectivity and show enhancements with six- and seven-membered ring carbenes.

Ruthenium(II) Complexes Having a Pincer‐Type Ligand with Two N‐Heterocyclic Carbene Moieties

Two novel RuII complexes, having 2,2′‐bipyridyl and a pincer‐type methylene‐bridged N‐heterocyclic carbene (NHC) ligand, were synthesized and characterized to evaluate the effects of structural features of the complexes on their redox and photochemical properties. The methylene‐bridged NHC ligand coordinated in a meridional manner and the isopropyl groups on the NHC rings exhibited intramolecular CH/π interaction with the 2,2′‐bipyridyl ligand, which played a role to strongly maintain the distorted ligand structure. In addition, the two Ru complexes exhibited reversible redox waves in the cyclic voltammograms and they were oxidized by an electron‐transfer oxidant to afford RuIII complexes, which were characterized by EPR spectroscopy and theoretical analyses.

Ru3(6-NHC)(CO)10]: synthesis, characterisation and reactivity of rare 46-electron tri-ruthenium clusters.

[Ru3(CO)12] reacts at room temperature with N-alkyl substituted 6-membered ring N-heterocyclic carbenes (6-NHC) to form [Ru3(6-NHC)(CO)10] (6-NHC = 6-iPr 1, 6-Et 2 and 6-Me 4), rare examples of coordinatively unsaturated (46-electron) ruthenium clusters. Complexes 1, 2 and 4 have been structurally characterised, along with the tetranuclear ruthenium cluster [Ru4(6-Et)2(CO)11] 3 that is formed along with 2. The degradation of the 6-iPr derivative 1 by pyrimidinium salt elimination helped to explain the poor activity of the complex in the catalytic acylation of pyridine.

Modulating the Bonding Properties of N-Heterocyclic Carbenes (NHCs): A Systematic Charge-Displacement Analysis.

In view of their intensive use as ligands in many reactions catalyzed by transition-metal complexes, modulation of the bonding properties of N-heterocyclic carbenes (NHCs) on a rational basis is highly desirable, which should enable optimization of current applications or even promote new functions. In this paper, we provide a quantitative analysis of the chemical bond between a metal fragment AuCl and a series of 29 different NHCs in [(NHC)AuCl] complexes. NHCs electronic properties are modified through: i) variation of the groups attached to the NHC nitrogen atoms or backbone; ii) change of unsaturation/size of the NHC ring; iii) inclusion of paracyclophane moieties; or iv) heteroatom substitution on the NHC ring. For evaluating the donation and back-donation components of the Dewar-Chatt-Duncanson (DCD) model in the NHC-AuCl bond, we apply the charge-displacement (CD) analysis within the NOCV (natural orbitals for chemical valence) framework, a methodology that avoids the constraint of using symmetrized structures. We show that modulation of the NHC bonding properties requires substantial modification of their structure, such as, for instance, insertion of two ketone groups into the NHC backbone (which enhances the π back-donation bond component and introduces an effective electronic communication within the NHC ring) or replacement of a nitrogen atom in the ring with an sp3 or sp2 carbon atom (which increases and decreases the π back-donation bond component, respectively). We extend our investigation by quantitatively comparing the NHC electronic structures for a subset of 13 NHCs in [(NHC)PPh] adducts, the 31 P NMR chemical shift values of which are experimentally available. The latter have been considered as a suitable tool for measuring the NHCs π acceptor properties [Bertrand et al., Angew. Chem. Int. Ed. 2013, 52, 2939-2943]. We show that information obtained using the metal fragment can be transferred to the PPh moiety and vice versa. However, the 31 P NMR chemical shift values only qualitatively correlate with the π acceptor properties of the NHCs, with the stronger π acidic carbenes as the most outliners.

Synthesis of Ester- and Phosphonate-Functionalized AuI -Imidazolylidene Chlorides through the Isonitrile Route.

Starting from DMSAuCl, isonitriles and functionalized propargylammonium salts in the presence of simple trimethylamine as auxiliary base, unsymmetrically substituted ester- and phosphonate-functionalized AuI -imidazolylidene complexes were synthesized in an easy-to-use modular one-pot template synthesis. In the course of the reaction, after the initial nucleophilic addition of the amine to the gold(I)-activated isonitrile, a Michael addition closes the N-heterocyclic carbene (NHC) ring. Then the remaining double bond migrates into the NHC ring, evidently a more stable position than the initial exocyclic double bond. These functional groups attached to the back bone of the NHC ligands represent ideal handles for a further modification of the system, for example an attachment to larger assemblies or heterogenization by an attachment to surfaces are conceivable.

Unsymmetrical NCN-pincer mononuclear and dinuclear nickel(ii) complexes of N-heterocyclic carbene (NHC): synthesis, structure and catalysis for Suzuki-Miyaura cross-coupling.

This report describes the synthesis and characterization of a family of unsymmetrical NCN pincer Ni(ii) complexes 2-8 with NHC-triazole arms. All of these complexes have been fully characterized by X-ray single crystal analysis, NMR spectroscopy, and elemental analysis. Complexes 2 and 4-6 were square planar with a chloride trans to the carbene carbon atoms. Complex 3 was a paramagnetic octahedral complex with its central metal surrounded by two NCN pincer ligands. Complexes 7 and 8 contain [(NHC)2Ni2-OH] moieties bearing a OH bridge. Both the [(NHC)2Ni2-OH] complexes 7 and 8 and [(NCNHCN)Ni-Cl] complexes 2 and 4-6 were synthesized similarly via the reactions of the in situ formed Ag-NHCs from the corresponding imidazolium salts with [NiCl2(PPh3)2]. The catalytic activities of all complexes for Suzuki-Miyaura cross-coupling were examined. Under the optimized conditions, complex 4 was active in the Suzuki-Miyaura cross-coupling reactions of aryl iodides and aryl bromides at 110 °C. Aryl chlorides were successfully coupled in the presence of triphenylphosphine as an additive.

Cationic Two-Coordinate Complexes of Pd(I) and Pt(I) Have Longer Metal-Ligand Bonds Than Their Neutral Counterparts

Summary One-electron oxidation of known ( t Bu 3 P) 2 M (1, M = Pd; 2, M = Pt) with [Ph 3 C][HCB 11 Cl 11 ] leads to two-coordinate, monovalent cations of the formula [( t Bu 3 P) 2 M][HCB 11 Cl 11 ] (3, M = Pd; 4, M = Pt), which also possess linear geometry but with elongated M–P bonds. Spectroscopic and computational studies consistently show that the unpaired electron of the d 9 configuration of 3 and 4 belongs to largely non-bonding orbitals: the s/d z2 hybrid for Pd and the degenerate d x2-y2 /d xy pair for Pt. We show that molecular-orbital-based arguments alone are incapable of predicting or rationalizing the observed M–P bond lengthening on oxidation; correct prediction and rationalization are achieved only by inclusion of electrostatic and Pauli effects. This emphasizes the dangers of interpreting any perturbative changes in bond metrics solely on the basis of energies and occupancies of molecular orbitals; the inclusion of electrostatic and Pauli components is essential to providing a more complete picture.

Quantitative Index of the Relative Ease of Formation and σ-Bonding Strength of N-Heterocyclic Carbenes.

An energy-based index of the ease of N-heterocyclic carbene (NHC) formation either by deprotonation of precursor salts to give neutral NHCs or deprotonation of heterocyclic mesomeric betaines to give anionic NHCs is described. This index (CREF; Carbene Relative Energy of Formation), which is easily calculated using DFT methods, also gives a quantitative measure of the relative σ-donor strength of NHCs. CREF index values for a wide range of known and unknown NHC ring systems are reported and their significance discussed.