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.     

New derivatives of indazole as electronically active materials

Synthesis and thermal, optical, electrochemical and photoelectrical properties of new indazole-based electroactive materials are reported. 1-Phenyl-5(6)-[N,N-(bisphenyl)]aminoindazoles and their methoxy-substituted analogues exhibit high thermal stabilities with the onset temperatures of thermal degradation ranging from 352 to 424 °C. The synthesized indazole derivatives form glasses with glass transition temperatures ranging from 35 to 39 °C. The synthesized compounds are electrochemically stable: their cyclic voltammograms show one reversible oxidation couple and no reduction waves. The ionization potentials of the solid samples of the synthesized materials are in the range of 5.3-5.9 eV. Methoxy-substituted derivatives show lower ionization potentials. Time-of-flight hole drift mobilities of 50% solid solution of 1-(4-methoxyphenyl)-5-{N,N-[bis(4-methoxyphenyl)]}aminoindazole in bisphenol Z polycarbonate reach 10⁻⁵ cm²/V s at high electric fields.     

Luminescent palladium(0) complexes bearing N-heterocyclic carbene and phosphine ligands

Palladium(0) complexes bearing a monodentate phosphine ligand and an N-heterocyclic carbene ligand have been prepared. In these complexes, photophysical properties of the complexes, [Pd(IPr)(PPh₃)] and [Pd(IPr)(P(o-tol)₃)] have been studied (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene). The emissive excited states have been tentatively assigned to ³MLCT. In addition to the results of the luminescent complexes, the synthesis of the related complexes, [Pd(O₂)(IPr)(P(m-tol)₃)] and [PdCl(CH₂Cl)(IPr)(P(MeOPh)₃)] (P(MeOPh)_3 = tris(pmethoxyphenyl)phosphine) have been studied and the structures were characterized by X-ray.     

Copolymers containing electronically isolated indolyl fragments as materials for optoelectronics

Monomer and its copolymers containing electronically isolated indolyl fragments were synthesized by multi-step synthetic route. The materials were examined by various techniques including thermogravimetry, differential scanning calorimetry, UV and fluorescence spectrometry as well as electron photoemission technique. The copolymers exhibit initial mass loss temperatures in the range of 259–321 °C and form amorphous films with glass transition temperatures of 102–122 °C. Thin layers of the materials demonstrate ionization potentials of about 5.7 eV. The copolymers were tested as host materials in electro-phosphorescent devices.     

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.     

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.     

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.     

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.     

Metal complexes as potential ligands: The deprotonation of aminephenolate metal complexes

The cationic nickel, copper and zinc complexes of tris-(2-hydroxybenzyl)-aminoethylamine (H6TrenSal) have been deprotonated using potassium hydroxide. The nickel complex can be sequentially deprotonated to form a series of compounds namely, [(H6TrenSal)Ni]⁺, [(H6TrenSal)Ni] and “[(H6TrenSal)Ni]K”. The latter is isolated as a mixture of species namely [{(H6TrenSal)Ni}K(EtOH)]₂, [{(H6TrenSal)Ni}K(EtOH)₂-μ-OH₂]₂ and [{(H6TrenSal)Ni}K(EtOH)₂-μ-EtOH]₂, which co-crystallise in a roughly 50:27.5:22.5 ratio. In contrast the deprotonation of [(H6TrenSal)M]⁺ (M = Cu, Zn) results in the formation of tetrameric complexes [({(H6TrenSal)Ni}K(OH₂)₂)₄(μ₄-OH₂)].     

Calcium monosilicates as components of composite materials

The structure and physicochemical properties of calcium monosilicates are studied using X-ray diffraction, atomic-force microscopy, scanning electron microscopy, thermogravimetric analysis, and optical spectrometry. It was shown that replacing titanium dioxide with calcium monosilicates for the production of composite materials on the basis of PVC (polyvinylchloride) allows for the obtainment of composites more tolerant to ultraviolet irradiation.     

Nitrogen-enriched bituminous coal-based active carbons as materials for supercapacitors

The paper presents the results of a study on obtaining N-enriched active carbons from bituminous coal and on testing its use as an electrode material in supercapacitors. The coal was carbonised, activated with KOH and ammoxidised by a mixture of ammonia and air at the ratio 1:3 at 300 °C or 350 °C, at different stages of the production, that is, at those of precursor, carbonisate, and active carbon. The products were microporous N-enriched active carbon samples of well-developed surface area reaching from 1577 to 2510 m²/g and containing 1.0 to 8.5 wt% of nitrogen. The XPS measurements have shown that in the active carbons enriched in nitrogen at the stage of precursor and at the stage of carbonisate, the dominant nitrogen species are the N-5 groups, while in the samples ammoxidised at the last stage of the treatment the dominant nitrogen species are the surface groups of imines and/or nitriles, probably accompanied by amines and amides. The paper reports the results of a comprehensive study of the effect of the structure and chemical composition of a series of active carbon samples of different properties on their capacity performance in water solutions of H₂SO₄ or KOH, with the behaviour of positive and negative electrodes analysed separately.     

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.     

Growth potential for soybean oil products as industrial materials

Crude soybean oil, as a major source of edible oil for the world, is available on such a scale that it serves additionally as the origin for many industrial applications and for such materials as phospholipids (lecithins, cephalins), tocopherols (for vitamin E), sterols (for pharmaceuticals) and recovered fatty acids from acidulated soapstocks. The latter always have offered the oleochemicals manufacturer a low cost source of valuable fatty acids, and soybean oil itself, after hydrogenation, serves as the most readily available, lowest cost source of 90% stearic acid from among all fats and oils. As an alternative to alkali refining and the soapstock produced, physical refining of the degummed soybean oil is a potential source for fatty acids and for recovery of larger amounts of valuable sterols and tocopherols, but this process severely degrades the oxidation stability of the fatty acids. The largest potentials for growth in industrial applications are for soybean oil itself in pesticide dispersion and grain dust control; triglycerides and fatty acids split therefrom for 90% stearate oleochemicals and selected food additivies; fatty acids from soapstocks up-graded medium-grade oleochemicals, medium-grade soaps for industrial cleaning operations, and in animal feeds and pet foods; phospholipid gums in fractionated and modified lecithins and cephalins; soy deodorizer distillates containing α-to copherol (vitamin E) and sterol-derived sex hormones. Inclusion of food additives, feed and pet food additives with the more usual industrial markets results in the conclusion that industrial utilization of soybean oil could reach 12% of total consumption in the U.S. within five years.     

Branched diphenylsilane derivatives containing electronically isolated indolyl moieties as host materials for blue organic light emitting diodes

Branched diphenylsilane derivatives with pendent indolyl fragments were synthesized and characterized. The compounds show high thermal stability with thermal decomposition starting at temperatures above 367 °C and ability to form glasses with glass-transition temperatures of 53-58 °C. The electron photoemission spectra of the layers of the synthesized compounds showed ionization potentials of ca. 5.85 eV. The derivatives were tested as host materials in phosphorescent OLEDs with iridium(III)[bis(4,6-difluorophenyl)-pyridinato-N,C2′]picolinate as the guest. The device with the host derivative containing four electronically isolated indolyl fragments exhibited the best overall performance with maximum current efficiency of about 12 cd/A.     

Fast condensation of cyclohexanone with 2-aminobenzonitrile at room temperature catalysed by an N-heterocyclic carbene

A fast condensation of cyclohexanone with 2-aminobenzonitrile catalysed by N-heterocyclic carbene 1,3-dipropylimidazole-2-ylidene (NHC-PPIm) at room temperature was discovered. NHC-PPIm was prepared via concentration of a 1,3-dipropylimidazolium hydroxide aqueous solution and showed excellent catalytic activity in the condensation reaction for the synthesis of quinazolinone. A possible catalytic mechanism was proposed based on the umpolung of cyclohexanone.     

Soft-templated mesoporous carbons as potential materials for oral drug delivery

Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride (HCl). Captopril and furosemide exhibited desorption kinetics over 30–40 h, and ranitidine. HCl had a complete release time of 5–10 h. As evident from the slow release kinetics, the mesoporous carbons have excellent potential for the controlled-release media of the specific drugs targeted towards oral delivery. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200–400 m² g⁻¹ and pore volume of 0.2–0.6 cm³ g⁻¹. The synthetic carbon has narrower pore widths and higher pore volume than the renewable counterpart and maintains a longer release time. The release kinetics reveals that the diffusivities of the drugs from carbon media are of equivalent magnitude (10⁻²² to 10⁻²⁴ m² s⁻¹). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecule by an order of magnitude. Thus, engineered pore morphology, along with its functionalization potential for specific interaction, can be exploited for optimal delivery system of a preferred drug.     

An efficient N-heterocyclic carbene based ruthenium-catalyst: Application towards the synthesis of esters and amides

A highly stable benzimidazolylidene based N-heterocyclic carbene (NHC) ruthenium catalyst was prepared starting with readily accessible starting materials. Under inert gas atmosphere and in air the catalyst showed high activity for the direct synthesis of esters from primary alcohols and of amides from primary alcohols and amines. Di-, tri-, and oligo-amides were obtained by using specific starting materials.     

Electrogenerated N-heterocyclic carbene: N-acylation of chiral oxazolidin-2-ones in ionic liquids

An electrochemical procedure for the N-acylation of chiral oxazolidin-2-ones, in the absence of volatile molecular organic solvents, has been set up via electrolyses of ionic liquid [bmim]BF₄ containing oxazolidin-2-ones followed by addition of saturated or unsaturated anhydrides. N-acyloxazolidin-2-ones were isolated in good to elevated yields. The electrochemically induced N-acylation of chiral oxazolidin-2-ones occurs with total retention of the absolute configuration of all the chiral atoms. The electrogenerated carbene (1-butyl-3-methyl-1H-imidazol-2-ylidene) has been indicated as the base involved in the deprotonation of chiral oxazolidin-2-ones.