N-heterocyclic carbene gold(I) and copper(I) complexes in C-H bond activation

Environmental concerns have and will continue to have a significant role in determining how chemistry is carried out. Chemists will be challenged to develop new, efficient synthetic processes that have the fewest possible steps leading to a target molecule, the goal being to decrease the amount of waste generated and reduce energy use. Along this path, chemists will need to develop highly selective reactions with atom-economical pathways producing nontoxic byproduct. In this context, C-H bond activation and functionalization is an extremely attractive method. Indeed, for most organic transformations, the presence of a reactive functionality is required. In Total Synthesis, the "protection and deprotection" approach with such reactive groups limits the overall yield of the synthesis, involves the generation of significant chemical waste, costs energy, and in the end is not as green as one would hope. In turn, if a C-H bond functionalization were possible, instead of the use of a prefunctionalized version of the said C-H bond, the number of steps in a synthesis would obviously be reduced. In this case, the C-H bond can be viewed as a dormant functional group that can be activated when necessary during the synthetic strategy. One issue increasing the challenge of such a desired reaction is selectivity. The cleavage of a C-H bond (bond dissociation requires between 85 and 105 kcal/mol) necessitates a high-energy species, which could quickly become a drawback for the control of chemo-, regio-, and stereoselectivity. Transition metal catalysts are useful reagents for surmounting this problem; they can decrease the kinetic barrier of the reaction yet retain control over selectivity. Transition metal complexes also offer important versatility in having distinct pathways that can lead to activation of the C-H bond. An oxidative addition of the metal in the C-H bond, and a base-assisted metal-carbon bond formation in which the base can be coordinated (or not) to the metal complexes are possible. These different C-H bond activation modes provide chemists with several synthetic options. In this Account, we discuss recent discoveries involving the versatile NHC-gold(I) and NHC-copper(I) hydroxide complexes (where NHC is N-heterocyclic carbene) showing interesting Br?nsted basic properties for C-H bond activation or C-H bond functionalization purposes. The simple and easy synthesis of these two complexes involves their halide-bearing relatives reacting with simple alkali metal hydroxides. These complexes can react cleanly with organic compounds bearing protons with compatible pK(a) values, producing only water as byproduct. It is a very simple protocol indeed and may be sold as a C-H bond activation, although the less flashy "metalation reaction" also accurately describes the process. The synthesis of these complexes has led us to develop new organometallic chemistry and catalysis involving C-H bond activation (metalation) and subsequent C-H bond functionalization. We further highlight applications with these reactions, in areas such as photoluminescence and biological activities of NHC-gold(I) and NHC-copper(I) complexes.     

Synthesis,characterization, and catalytic behavior of mono- and bimetallic ruthenium(II) and iridium(III) complexes supported by pyridine-functionalized N-heterocyclic carbene ligands

We have prepared and characterized five unreported ruthenium(II) and iridium(III) complexes supported by pyridine-functionalized N-heterocyclic carbene ligands including a bimetallic iridium(III) complex. When activated, all complexes are active catalysts for the transfer hydrogenation of acetophenone.     

Poly(l-lactide) initiated by silver N-heterocyclic carbene complexes: synthesis, characterization and properties

Poly(l-lactide) (PLLA) was successfully synthesized by ring-opening polymerization (ROP) in bulk using silver N-heterocyclic carbene (Ag–NHC) complex. The effect of reaction time, temperature and monomer/initiator ratio on polymerization process were determined. The optimum conditions were found as 130 °C, 4 h and M/I molar ratio of about 100. The polymers were characterized by FTIR, ¹H-NMR, GPC and TG. High-molecular-weight PLLA (M _w = 3.78 × 10⁴, M _n = 1.91 × 10⁴, PDI = 1.97) was synthesized by the ROP of l-lactide (LLA) with bis-(N-methyl N′-dodecylimidazole) silver(I) di-bromo argentate (1a) in bulk. The effect of different N-substituted ligand groups on the polymerization was studied. The antimicrobial activity of the synthesized polymers were investigated by using minimum inhibitory concentration test against gram positive (Staphylococcus aureus) and gram negative (Escherichia coli and Pseudomonas aeruginosa). It was observed that the synthesized polymers displayed moderate antimicrobial activity.     

The development and catalytic uses of N-heterocyclic carbene gold complexes

Gold has emerged as a powerful synthetic tool in the chemist's arsenal. From the early use of inorganic salts such as AuCl and AuCl(3) as catalysts, the field has evolved to explore ligands that fine-tune reactivity, stability, and, more recently, selectivity in gold-mediated processes. Substrates generally contain alkenes or alkynes, and they usually involve straightforward protocols in air with solvents that can often times be of technical grade. The actual catalytic species is the putative cationic gold(I) complex [Au(L)](+) (where L is a phosphorus-based species or N-heterocyclic carbene, NHC). The early gold systems bearing phosphine and phosphite ligands provided important transformations and served as useful mechanistic probes. More recently, the use of NHCs as ligands for gold has rapidly gained in popularity. These two-electron donor ligands combine strong σ-donating properties with a steric profile that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the gold-NHC complexes have been used as well-defined precatalysts and have permitted the isolation of reactive single-component systems that are now used instead of the initial [Au(L)Cl]/silver salt method. Because some are now commercially available, NHC-containing gold(I) complexes are gathering increasing interest. In this Account, we describe the chronological development of this chemistry in our laboratories, highlighting the advantages of this family of gold complexes and reviewing their synthesis and applications in catalysis. We first outline the syntheses, which are straightforward. The complexes generally exhibit high stability, allowing for indefinite storage and easy handling. We next consider catalysis, particularly examining efficacy in cycloisomerization, other skeletal rearrangements, addition of water to alkynes and nitriles, and C-H bond activation. These processes are quite atom-economical, and in the most recent C-H reactions the only byproduct is water. State-of-the-art methodology now involves single-component catalysts, precluding the need for costly silver co-catalysts. Remarkably, the use of an NHC as a supporting ligand has permitted the isolation of [Au(L)(S)](+) species (where S is a solvent molecule such as a nitrile), which can act as single-component catalysts. Some improvements are still needed, as the single components are most often synthesized with a silver reagent. Owing to the stabilizing effect of NHC coordination, some NHC-containing systems can catalyze extremely challenging reactions (at temperatures as high as 140 °C) and react at very low loadings of gold (ppm levels). Our latest developments deal with C-H bond functionalization and hold great promise. We close with a selection of important developments by the community with gold-NHC complexes. As demonstrated by the turns and twists encountered during our own journey in the gold-NHC venture, the chemistry described here, combining fundamental organometallic, catalytic, and organic methodology, remains rich in opportunities, especially considering that only a handful of gold(I) architectures has been studied. We hope this Account will encourage young researchers to explore this emerging area, as the adage "the more you do, the more you have to do" surely holds true in gold-mediated catalysis.     

Macrocyclic silver and gold complexes containing bis (N-heterocyclic carbene) ligand: Synthesis and structural characterization

Silver and gold complexes, [Ag₂(L)₂](PF₆)₂ and [Au₂(L)₂](PF₆)₂, supported by but-2-yne-1,4-diyl linked bis(N-heterocyclic carbene) ligand have been prepared and structurally characterized. The complexes display novel twisted macrocyclic conformation and weak intramolecular metal–metal interaction. The complexes are intensely emissive in their solid states.     

Hydrogenation of ethylene carbonate catalyzed by lutidine-bridged N-heterocyclic carbene ligands and ruthenium precursors

A series of air and moisture-stable lutidine-bridged N-heterocyclic carbene (NHC) ligands and commercial Ru precursors were applied as catalysts for hydrogenation of ethylene carbonate to glycol and methanol. N-Butyl-substituted CNC-pincer ligand L1 and RuHCl(CO)(PPh₃)₃ catalytic system exhibited the highest catalytic activity with 99% conversion of ethylene carbonate, 92% glycol and 42% methanol yields. The high catalytic activity was attributed to the in-situ formation of Ru-NHC complexes in the presence of base. This facile, stable and efficient catalytic system provided a new method for the indirect conversion of CO₂.     

Mononuclear metal-o(2) complexes bearing macrocyclic N-tetramethylated cyclam ligands

Metalloenzymes activate dioxygen to carry out a variety of biological reactions, including the biotransformation of naturally occurring molecules, oxidative metabolism of xenobiotics, and oxidative phosphorylation. The dioxygen activation at the catalytic sites of the enzymes occurs through several steps, such as the binding of O(2) at a reduced metal center, the generation of metal-superoxo and -peroxo species, and the O-O bond cleavage of metal-hydroperoxo complexes to form high-valent metal-oxo oxidants. Because these mononuclear metal-dioxygen (M-O(2)) adducts are implicated as key intermediates in dioxygen activation reactions catalyzed by metalloenzymes, studies of the structural and spectroscopic properties and reactivities of synthetic biomimetic analogues of these species have aided our understanding of their biological chemistry. One particularly versatile class of biomimetic coordination complexes for studying dioxygen activation by metal complexes is M-O(2) complexes bearing the macrocyclic N-tetramethylated cyclam (TMC) ligand. This Account describes the synthesis, structural and spectroscopic characterization, and reactivity studies of M-O(2) complexes bearing tetraazamacrocyclic n-TMC ligands, where M ═ Cr, Mn, Fe, Co, and Ni and n = 12, 13, and 14, based on recent results from our laboratory. We have used various spectroscopic techniques, including resonance Raman and X-ray absorption spectroscopy, and density functional theory (DFT) calculations to characterize several novel metal-O(2) complexes. Notably, X-ray crystal structures had shown that these complexes are end-on metal-superoxo and side-on metal-peroxo species. The metal ions and the ring size of the macrocyclic TMC ligands control the geometric and electronic structures of the metal-O(2) complexes, resulting in the end-on metal-superoxo versus side-on metal-peroxo structures. Reactivity studies performed with the isolated metal-superoxo complexes reveal that they can conduct electrophilic reactions such as oxygen atom transfer and C-H bond activation of organic substrates. The metal-peroxo complexes are active oxidants in nucleophilic reactions, such as aldehyde deformylation. We also demonstrate a complete intermolecular O(2)-transfer from metal(III)-peroxo complexes to a Mn(II) complex. The results presented in this Account show the significance of metal ions and supporting ligands in tuning the geometric and electronic structures and reactivities of the metal-O(2) intermediates that are relevant in biology and in biomimetic reactions.     

Synthesis of poly(triarylamine)s by C–N coupling catalyzed by (N-heterocyclic carbene)-palladium complexes

The use of (N-heterocyclic carbene)-palladium complexes as precatalysts for the synthesis of poly(triarylamine)s by C–N coupling is reported. Effective control of the molecular weight distribution by in situ end-capping during the polymerization was found to be important for application of these polymers as the charge transporting layers of OFETs.     

Surveying sterically demanding N-heterocyclic carbene ligands with restricted flexibility for palladium-catalyzed cross-coupling reactions

Heterocyclic carbenes (NHCs), especially monodentate ones, have become the ligand of choice for many transition-metal-catalyzed transformations. They generally form highly stable complexes, have strong sigma-donor character, and have a unique shape that can be used to generate sterically demanding ligands.In this Account, we survey recent developments in the design and synthesis of some sterically demanding NHCs with a particularly strong influence on the metal's coordination sphere. We show the successful and insightful application of these ligands in transition-metal catalysis. First, we discuss methods for determining and classifying the electronic and steric properties of NHCs. In addition, we present data on the most important NHC ligands.The selective variation of either electronic or steric parameters of NHCs, and therefore of the catalyst, allows for the optimization of the reaction. Thus, we prepared several series of differentially substituted NHC derivatives. However, because the substituents varied were not directly connected to the carbene carbon, it was difficult to induce a large electronic variation. In contrast, an independent variation of the ligands' steric properties was more straightforward. We highlight three different classes of very sterically demanding NHCs that allow this kind of a steric variation: imidazo[1,5-a]pyridine-3-ylidenes, bioxazoline-derived carbenes (IBiox), and cyclic (alkyl)(amino)carbenes (CAAC).These latter NHC ligands can facilitate a number of challenging cross-coupling reactions. Successful transformations often require a monoligated palladium complex as the catalytically active species, and the sterically demanding NHC ligand favors this monoligated complex. In addition, the electron-rich NHC facilitates difficult oxidative addition steps. Moreover, the conformational flexibility of the ligands can facilitate the formation of catalytically active species and hemilabile interactions, such as agostic or anagostic bonds, as well as stabilize coordinatively unsaturated catalyst species. The increasing level of understanding of the role of NHC ligands in transition-metal catalysis will soon allow the design of even more sophisticated ligand systems.     

The potential of N-heterocyclic carbene complexes as components for electronically active materials

The application of N-heterocyclic carbene complexes as active sites in materials other than catalysis has been remarkably scarce. Inspired by the - often misleading - 'carbene' label, which implies a substantial degree of M = C pi bonding, we have been interested in evaluating the potential of N-heterocyclic carbene complexes as building blocks for constructing electronically active materials. Electron mobility via the metal-carbon bond has been investigated in monometallic imidazol-2-ylidene complexes and subsequently expanded to polymetallic systems. In particular, ditopic benzobisimidazolium-derived ligands have been explored for the fabrication of bimetallic molecular switches and main-chain conjugated organometallic polymers. Electrochemical analyses have allowed the degree of electronic coupling between the metal sites to be quantified and the key parameters that govern the intermetallic communication to be identified.     

Mixed-ligand platinum and palladium complexes based on dinitrogen chelating ligands and a pyridine bearing the nitronylnitroxide radical

Novel cationic mixed-ligand palladium and platinum complexes based on the chelating ligands 4,7-dimethyl-1,10-phenanthroline and 2,2′-bipyridine with a pyridine bearing the nitronylnitroxide radical are reported. The synthesis, X-ray crystal structures and magnetic properties of the two complexes [Pd(4,7-dimethyl-1,10-phenanthroline)(NIT-pPy)₂](PF₆)₂. DMF and [Pt(2,2′-bipyridine-N,N′)(NIT-pPy)₂](PF₆)₂ · 0.25H₂O, (where NIT-pPy = 2-(p-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) are described. The two metal complexes show a strained square planar geometry. Short intermolecular contacts take place through the nitroxide groups and weak intermolecular antiferromagnetic interactions are dominant at low temperature.     

Synthesis,structural characterization,opto-electrical properties of Ir(III) complexes with imidazolium-based carbene ligands

A series of Ir(III) complexes with N–heterocyclic carbenes (NHC) ligands (1–3) were synthesized and characterized. The opto-electrical properties of these complexes were investigated spectroscopically, electrochemically and theoretically. All complexes exhibit ligand-based ¹π,π* transitions in the UV region, ¹MLCT absorption in the UV region, and weak low energy ³π, π* transition in visible region. These complexes all exhibit blue phosphorescence at both room temperature and 77 K, which is dominated by ³π,π* character. DFT calculation results indicate their lowest unoccupied molecular orbitals (LUMO) from − 0.47 to − 0.33 eV and the highest occupied molecular orbitals (HOMO) from − 4.97 to − 5.33 eV. The opto-electrical properties can be influenced drastically by NHC ligands, which would be useful for rational design of optical functional materials.     

Enantioselective hydroformylation of olefins catalyzed by rhodium(I) complexes of chiral phosphine–phosphite ligands

Using Rh(I) complexes of chiral phosphine–phosphites, hydroformylation of such a variety of olefins as aryl–substituted, alkyl–substituted, and heteroatom–substituted ones proceeded in high enantioselectivity. A trigonal bipyramidal RhH(CO)₂(phosphine–phosphite) complex is suggested as the active species, in which the hydride and the phosphite moiety are located at the apical positions. This revised version was published online in June 2006 with corrections to the Cover Date.     

First synthesis of a palladium(0)-containing multimetallic system based on hemilabile pyridylthioether ligands

The complexation of a multidentate ligand based on 2,6-bis(ethylthiomethyl)pyridine units with Pd₂(DBA)₃CHCl₃ in the presence of activated olefins afforded a new tripalladium(0) system.     

Polymerization of 2,2′‐dimethyltrimethylene carbonate by lutetium complexes bearing amino‐phosphine ligands

A series of lutetium alkyl, amino, and guanidinato complexes based upon an amino‐phosphine ligand framework had been prepared. These complexes were applied to initiate ring‐opening polymerization of 2,2′‐dimethyltrimethylene carbonate (DTC). The type of the initiator significantly influenced the catalytic activity of these complexes in a trend as follows: alkyl ≈ guanidinate > amide, whereas the complexes with flexible backbone between P and N atoms within the ligand exhibited higher activity than those with rigid backbone. The isolated PDTC had bimodal‐mode molecular weight distribution. The molecular weights of each fraction increased linearly with the conversion, indicating that there might be two active species. This had been confirmed by analyses of oligomeric DTC living species and oligomer with NMR technique as the metal‐alkoxide and the four‐membered metallocyclic lactate. Kinetic investigation displayed that the polymerization rate was the first order with the monomer concentration. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Organometallic diaqua complexes of palladium(II)

The protonation of [(C₆F₅)LPd(μ-OH)₂PdL(C₆F₅)] by triflic acid (CF₃SO₃H) results in the formation of the diaqua complexes [Pd(C₆F₅)L(H₂O)₂][CF₃SO₃] (L=PPh₃ (1) or AsPh₃ (2)). The crystal structure of 2 was elucidated by X-ray diffraction analysis revealing the presence of tetrameric units involving hydrogen bonds.