Second-generation Ruthenium Research Articles

Hoveyda-Grubbs type complexes with ruthenium-pnictogen/halcogen/halogen coordination bond. Synthesis, catalytic activity, applications.

Catalytic olefin metathesis using Hoveyda-Grubbs-type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs-type complexes, which include a Het→Ru donor-acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs-type complexes with donor-acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers. Bibliography includes 174 references.

New Insights into the Catalytic Activity of Second Generation Hoveyda–Grubbs Complexes Having Phenyl Substituents on the Backbone

One of the most effective synthetic pathways to produce unsaturated compounds and polymers, meant for both industrial and pharmaceutical applications, is olefin metathesis. These useful reactions are commonly promoted by ruthenium-based precatalysts, namely the second-generation Grubbs’ catalyst (GII) and complexes bearing a styrenyl ether ligand, referred to as the second-generation Hoveyda–Grubbs’ catalyst (HGII). By altering the steric and electronic characteristics of substituents on the backbone and/or on the nitrogen atoms of the NHC ligand, it is possible to increase the reactivity and stability of second-generation ruthenium catalysts. The synthesis of an HG type II complex bearing two anti-phenyl backbone substituents (anti-HGIIPh-Mes) with mesityl N-substituents is reported. The catalytic performances of the new complex were investigated in standard ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP) and compared to those of the analogue complex syn-HGIIPh-Mes and to the classic HGII complex. A thorough analysis of the temperature dependence of the performances, along with a detailed comparison with the commercially available HGII, is conducted. The HGIIPh-Mes complexes are more thermally stable than their parent HGII, as shown by the fact that their activity in the ROMP of 5-ethylidene-2-norbornene does not alter when the polymerization is carried out at room temperature after the complexes have been held at 180 °C for two hours, making them particularly interesting for materials applications.

Pseudopeptidic Polymer Microsphere-Filled Liquid Crystals as High-Performance Light-Scattering Switches

We, herein, report the fabrication of light-scattering switches from polymer microsphere-filled liquid crystals (PFLCs) using pseudopeptidic bottlebrush polymers. A simple method of precipitation of a polymer using the 4-cyano-4′-pentylbiphenyl (5CB) nonsolvent is employed for the preparation of PFLC devices. For this, a series of phenylalanine (Phe)-based bottlebrush polymers having different chain lengths are synthesized by ring-opening metathesis polymerization (ROMP) using the Grubbs second-generation ruthenium catalyst and used in a nematic liquid crystal (LC) matrix. The developed PFLC devices are well-characterized using various ultramicroscopic techniques such as field-emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and polarizing optical microscopy (POM). For the first time, the effect of the molecular weight of a polymer on electro-optic (E-O) properties of PFLC is investigated. PFLCs show significant differences in microsphere size, required operating voltage, transmittance, contrast ratio (CR ratio), memory effect, and switching speed upon subtle variation of the dopant polymer units. Overall, we demonstrated that the chain length of a polymer plays a crucial role in controlling the performance of PFLC devices. The presented methodology offers promising possibilities for the fabrication of PFLC-based switchable scattering devices with improved performance for optoelectronic applications.

Specialized Ruthenium Olefin Metathesis Catalysts Bearing Bulky Unsymmetrical NHC Ligands: Computations, Synthesis, and Application

Second-generation ruthenium olefin metathesis catalysts were investigated with systematic variation of the unsymmetrical uNHC ligands. Depending on the uNHC steric bulk, the catalysts exhibited dif...

SIMes/PCy3mixed ligand-coordinated alkyl group-tagged ruthenium indenylidene complexes: Synthesis, characterization and metathesis activity

We report on the synthesis and characterization of SIMes/PCy3 mixed ligand-coordinated second-generation ruthenium catalysts, bearing various 3-alkyl-1-indenylidene ligands, denoted as RuCl2(3-alkyl-1-indenylidene)(SIMes)(PCy3), in which alkyl is isopropyl (4f), tert-butyl (4g) or cyclohexyl (4h). The characterization of complexes 4f–4h was performed using infrared spectroscopy, elemental analysis, high-resolution mass spectrometry and NMR spectroscopy. In addition, the configuration of complexes 4f and 4g was analyzed using single-crystal X-ray diffraction analysis. The catalytic activities of 4f–4h were evaluated in the olefin metathesis reaction of the ring-closing metathesis of diethyl diallylmalonate, and the ring-opening metathesis polymerization of cis,cis-cyclooctadiene in comparison with the reference complex 4a. The results reveal that all complexes 4a and 4f–4h exhibit similar catalytic activity towards the tested substrates. Careful analysis of the catalyst performance and single-crystal X-ray diffraction data of the obtained complexes reveals that the steric modification on the 3-alkyl group shows a negligible influence on the ligand congestion around the ruthenium center as well as on the catalytic activities in the metathesis reactions.

An Initiation Kinetics Prediction Model Enables Rational Design of Ruthenium Olefin Metathesis Catalysts Bearing Modified Chelating Benzylidenes.

Rational design of second-generation ruthenium olefin metathesis catalysts with desired initiation rates can be enabled by a computational model that depends on a single thermodynamic parameter. Using a computational model with no assumption about the specific initiation mechanism, the initiation kinetics of a spectrum of second-generation ruthenium olefin metathesis catalysts bearing modified chelating ortho-alkoxy benzylidenes were predicted in this work. Experimental tests of the validity of the computational model were achieved by the synthesis of a series of ruthenium olefin metathesis catalysts and investigation of initiation rates by UV/Vis kinetics, NMR spectroscopy, and structural characterization by X-ray crystallography. Included in this series of catalysts were thirteen catalysts bearing alkoxy groups with varied steric bulk on the chelating benzylidene, ranging from ethoxy to dicyclohexylmethoxy groups. The experimentally observed initiation kinetics of the synthesized catalysts were in good accordance with computational predictions. Notably, the fast initiation rate of the dicyclohexylmethoxy catalyst was successfully predicted by the model, and this complex is believed to be among the fastest initiating Hoveyda-Grubbs-type catalysts reported to date. The compatibility of the predictive model with other catalyst families, including those bearing alternative NHC ligands or disubstituted alkoxy benzylidenes, was also examined.

Disentangling Ligand Effects on Metathesis Catalyst Activity: Experimental and Computational Studies of Ruthenium-Aminophosphine Complexes.

Second-generation ruthenium olefin metathesis catalysts bearing aminophosphine ligands were investigated with systematic variation of the ligand structure. The rates of phosphine dissociation ( k1; initiation rate) and relative phosphine reassociation ( k-1) were determined for two series of catalysts bearing cyclohexyl(morpholino)phosphine and cyclohexyl(piperidino)phosphine ligands. In both cases, incorporating P-N bonds into the architecture of the dissociating phosphine accelerates catalyst initiation relative to the parent [Ru]-PCy3 complex; however, this effect is muted for the tris(amino)phosphine-ligated complexes, which exhibit higher ligand binding constants in comparison to those with phosphines containing one or two cyclohexyl substituents. These results, along with X-ray crystallographic data and DFT calculations, were used to understand the influence of ligand structure on catalyst activity. Especially noteworthy is the application of phosphines containing incongruent substituents (PR1R'2); detailed analyses of factors affecting ligand dissociation, including steric effects, inductive effects, and ligand conformation, are presented. Computational studies of the reaction coordinate for ligand dissociation reveal that ligand conformational changes contribute to the rapid dissociation for the fastest-initiating catalyst of these series, which bears a cyclohexyl-bis(morpholino)phosphine ligand. Furthermore, the effect of amine incorporation was examined in the context of ring-opening metathesis polymerization, and reaction rates were found to correlate well with catalyst initiation rates. The combined experimental and computational studies presented in this report reveal important considerations for designing efficient ruthenium olefin metathesis catalysts.

Regioselectivity of Stoichiometric Metathesis of Vinylsilanes with Second-Generation Grubbs Catalyst: A Combined DFT and Experimental Study

The regioselectivity of metathesis reactions of trisubstituted vinylsilanes H2C═CHSiR3 (SiR3 = SiCl3, SiCl2Me, SiClMe2, SiMe3, Si(OEt)3) with the second-generation ruthenium alkylidene complex has been studied theoretically, by density functional theory (DFT), and experimentally. The DFT results indicate that cycloreversion is the rate-determining step and the formation of a thermodynamically stable ruthenium methylidene complex and PhCH═CHSiR3 is generally preferred. However, the regioselectivity of the process can be also governed by the relative stabilities of the ruthenacyclobutane intermediates, which depend on the electronic and steric properties of the SiR3 substituent. Higher stability of α,β-disubstituted ruthenacyclobutanes in comparison to α,α-disubstituted ruthenacyclobutanes is predicted, in contrast to the corresponding intermediates formed during metathesis of common α-olefins. The stabilizing Ru–Cβ interaction in the ring is strengthened by the electron-donor SiR3 substituent at Cβ. The ex...

On the chloride lability in electron-rich second-generation ruthenium benzylidene complexes

A series of electron-rich second-generation cis-dichloro ruthenium aldehyde-chelating benzylidene complexes was prepared, characterized, and tested in typical ring-opening metathesis polymerization (ROMP) experiments. The benzylidene precursors were prepared via etherification of the hydroxyl group and vinylation at position 2 of 2-bromo-5-hydroxy-4-methoxybenzaldehyde. The corresponding ruthenium complexes were obtained from a carbene exchange reaction and were characterized by a cis-dichloro arrangement. A pronounced lability of the chloride ligand trans to the N-heterocyclic carbene ligand in methanol was observed and it was shown that this feature is responsible for a particularly slow ROMP in this solvent.

Origins of initiation rate differences in ruthenium olefin metathesis catalysts containing chelating benzylidenes.

A series of second-generation ruthenium olefin metathesis catalysts was investigated using a combination of reaction kinetics, X-ray crystallography, NMR spectroscopy, and DFT calculations in order to determine the relationship between the structure of the chelating o-alkoxybenzylidene and the observed initiation rate. Included in this series were previously reported catalysts containing a variety of benzylidene modifications as well as four new catalysts containing cyclopropoxy, neopentyloxy, 1-adamantyloxy, and 2-adamantyloxy groups. The initiation rates of this series of catalysts were determined using a UV/vis assay. All four new catalysts were observed to be faster-initiating than the corresponding isopropoxy control, and the 2-adamantyloxy catalyst was found to be among the fastest-initiating Hoveyda-type catalysts reported to date. Analysis of the X-ray crystal structures and computed energy-minimized structures of these catalysts revealed no correlation between the Ru-O bond length and Ru-O bond strength. On the other hand, the initiation rate was found to correlate strongly with the computed Ru-O bond strength. This latter finding enables both the rationalization and prediction of catalyst initiation through the calculation of a single thermodynamic parameter in which no assumptions about the mechanism of the initiation step are made.

Ruthenium catalysts bearing a benzimidazolylidene ligand for the metathetical ring-closure of tetrasubstituted cycloolefins.

Deprotonation of 1,3-di(2-tolyl)benzimidazolium tetrafluoroborate with a strong base afforded 1,3-di(2-tolyl)benzimidazol-2-ylidene (BTol), which dimerized progressively into the corresponding dibenzotetraazafulvalene. The complexes [RhCl(COD)(BTol)] (COD is 1,5-cyclooctadiene) and cis-[RhCl(CO)2(BTol)] were synthesized to probe the steric and electronic parameters of BTol. Comparison of the percentage of buried volume (%VBur) and of the Tolman electronic parameter (TEP) of BTol with those determined previously for 1,3-dimesitylbenzimidazol-2-ylidene (BMes) revealed that the two N-heterocyclic carbenes displayed similar electron donicities, yet the 2-tolyl substituents took a slightly greater share of the rhodium coordination sphere than the mesityl groups, due to a more pronounced tilt. The anti,anti conformation adopted by BTol in the molecular structure of [RhCl(COD)(BTol)] ensured nonetheless a remarkably unhindered access to the metal center, as evidenced by steric maps. Second-generation ruthenium-benzylidene and isopropoxybenzylidene complexes featuring the BTol ligand were obtained via phosphine exchange from the first generation Grubbs and Hoveyda-Grubbs catalysts, respectively. The atropisomerism of the 2-tolyl substituents within [RuCl2(=CHPh)(PCy3)(BTol)] was investigated by using variable temperature NMR spectroscopy, and the molecular structures of all four possible rotamers of [RuCl2(=CH-o-O(i)PrC6H4)(BTol)] were determined by X-ray crystallography. Both complexes were highly active at promoting the ring-closing metathesis (RCM) of model α,ω-dienes. The replacement of BMes with BTol was particularly beneficial to achieve the ring-closure of tetrasubstituted cycloalkenes. More specifically, the stable isopropoxybenzylidene chelate enabled an almost quantitative RCM of two challenging substrates, viz., diethyl 2,2-bis(2-methylallyl)malonate and N,N-bis(2-methylallyl)tosylamide, within a few hours at 60 °C.

Impact of Electronic Modification of the Chelating Benzylidene Ligand in cis-Dichloro-Configured Second-Generation Olefin Metathesis Catalysts on Their Activity

A series of electronically modified second-generation cis-dichloro ruthenium ester chelating benzylidene complexes was prepared, characterized, and benchmarked in a typical ring-opening metathesis polymerization (ROMP) experiment. The electronic tuning of the parent chelating benzylidene ligand (2-ethyl ester benzylidene) was achieved by substitution at the 4- and 5-positions with electron-withdrawing nitro or electron-donating methoxy groups. The effect of the electronic tuning on the cis–trans isomerization process was studied experimentally and theoretically. Density functional theory calculations clearly revealed the influence of electronic modification on the relative stability between the cis and trans isomers, which is decisive for the activity of the studied compounds as initiators in ROMP.

Synthesis of C60-containing Polymers by Ring-opening Metathesis Co-polymerization of a C60-cyclopentadiene Cycloadduct and N-(cycloheptyl)-endo-norbornene-5,6-dicarboximide and their Application in a Photovoltaic Device

A C60-cyclopentadiene cycloadduct and N-(cycloheptyl)-endo-norbornene-5,6-dicarboximide were utilized as co-monomers in ring-opening metathesis polymerization (ROMP) reactions to afford a series of polymers containing C60 in varying ratios. The polymerization reactions were catalyzed by the Grubbs second-generation ruthenium catalyst, and the co-polymers formed were investigated by spectroscopic and thermal techniques. The photovoltaic behavior of the new materials was studied by the construction of a simple sandwich-type photovoltaic cell. Under irradiation we concluded that the C60 in the copolymers simultaneously accelerated both the charge separation in the polymer and the charge recombination between the electrons in the TiO2 and the electrolyte.

Robust and Selective Metathesis Catalysts for Oleochemical Applications

The screening of known ruthenium alkylidene complexes in the ethenolysis of methyl oleate shows that the Grubbs-type Ru-catalysts bearing two phosphine donor ligands exhibit high selectivity for the formation of terminal olefins. Second-generation ruthenium catalysts promote almost the exclusive formation of self-metathesis products. Complexes with chelating alkylidene moieties (Hoveyda-type) generally exhibit poor selectivity for both ethenolysis and self-metathesis products. Complexes 2b and 2d promote self-metathesis of methyl oleate with catalyst loading of 2 ppm without significant isomerization up to 110 °C (using 2d) and up to 150 °C (using 2b).

A New Tandem Cross Metathesis-Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams

A new tandem cross metathesis–intramolecular aza-Michael­ reaction in which an α,α-difluorinated amide serves as a source of nucleophilic nitrogen is described. This process gives rise to a new family of fluorinated γ- and δ-lactams. The tandem protocol is catalyzed by the Hoveyda–Grubbs second-generation ruthenium catalyst with titanium(IV) tetraisopropoxide as a co-catalyst and it is highly efficient when conjugated ketones are used as the Michael acceptors. With conjugated esters, however, it is necessary to perform a step-by-step procedure in which the cyclization event is activated by the addition of a base. An asymmetric version of the process is also evaluated.

The Doping Effect of Fluorinated Aromatic Solvents on the Rate of Ruthenium‐Catalysed Olefin Metathesis

A study concerning the effect of using a fluorinated aromatic solvent as the medium for olefin metathesis reactions catalysed by ruthenium complexes bearing N-heterocyclic carbene ligands is presented. The use of fluorinated aromatic hydrocarbons (FAH) as solvents for olefin metathesis reactions catalysed by standard commercially available ruthenium pre-catalysts allows substantially higher yields of the desired products to be obtained, especially in the case of demanding polyfunctional molecules, including natural and biologically active compounds. Interactions between the FAH and the second-generation ruthenium catalysts, which apparently improve the efficiency of the olefin metathesis transformation, have been studied by X-ray structure analysis and computations, as well as by carrying out a number of metathesis experiments. The optimisation of reaction conditions by using an FAH can be regarded as a complementary approach for the design of new improved ruthenium catalysts. Fluorinated aromatic solvents are an attractive alternative medium for promoting challenging olefin metathesis reactions.

Ring-opening metathesis and ring-closing metathesis of bicyclo[4.2.0]octene-ynes: Application to the synthesis of tricyclic compounds

Ring-opening metathesis and ring-closing metathesis (ROM-RCM) of bicyclo[4.2.0]octene-ynes and their application to the synthesis of tricyclic derivatives have been demonstrated using a second-generation ruthenium carbene complex. When bicycloalkene having a propargylamino group as an alkyne tether was reacted with a second-generation ruthenium carbene complex under an ethylene atmosphere, ROM-RCM proceeded to give tricyclic heterocycles in good yield. On the other hand, when the effect of the substituent on the alkyne was examined, cross metathesis (CM) of the alkyne part with ethylene proceeded to provide a conjugated diene derivative.

Antiproliferative activity of chelating N,O- and N,N-ruthenium(ii) arene functionalised poly(propyleneimine) dendrimer scaffolds

Chelating neutral (N,O) and cationic (N,N) first- and second-generation ruthenium(II) arene metallodendrimers based on poly(propyleneimine) dendrimer scaffolds were obtained from dinuclear arene ruthenium precursors by reactions with salicylaldimine and iminopyridyl dendritic ligands, respectively. The N,N cationic complexes were isolated as hexafluorophosphate salts and were characterised by NMR and IR spectroscopy, and MALDI-TOF mass spectrometry. Related mononuclear complexes were obtained in a similar manner and their molecular structures have been determined by X-ray diffraction analysis. The cytotoxicities of the mono- and multinuclear complexes were established using A2780 and A2780cisR human ovarian carcinoma cancer cell lines.

Application of well-defined ruthenium alkylidenes to the ROMP of norbornene derivatives: Methoxyphenyl-substituted polynorbornene dicarboximides

The applicability of ruthenium alkylidenes as initiators in the ring opening metathesis polymerization (ROMP) of methoxyphenyl group containing norbornene derivatives has been investigated. The synthesis and polymerization of exo- N-4-methoxyphenyl-oxanorbornene-5,6-dicarboximide (MeOPhONDI) and exo- N-4-methoxyphenyl-norbornene-5,6-dicarboximide (MeOPhNDI) are reported. Polynorbornene derivatives were obtained via ROMP using first - and second-generation ruthenium alkylidene initiators. The structural properties of the polynorbornene derivatives were analyzed by NMR, DSC and GPC. Analyses of the polymer microstructures indicate that polymers contain trans stereoconfiguration of the double bonds (55–86% trans-content). The glass transition temperatures of the polymers obtained from exo-monomers are higher than 211 °C.

Well-Defined Silica-Supported Olefin Metathesis Catalysts

Two triethoxysilyl-functionalized N-heterocyclic carbene ligands have been synthesized and used to prepare the corresponding second-generation ruthenium olefin metathesis catalysts. These complexes were then grafted onto silica gel, and the resulting materials were efficient heterogeneous catalysts for a number of metathesis reactions. The solid-supported catalysts were shown to be recyclable over a number of reaction cycles, and no detectable levels of ruthenium were observed in reaction filtrates (ruthenium concentration of filtrate <5 ppb).