Benzylidene Ligand Research Articles

Reactivity regulation for olefin metathesis-catalyzing ruthenium complexes with sulfur atoms at the terminal of 2-alkoxybenzylidene ligands.

For regulating the olefin metathesis (OM) activity of the Hoveyda-Grubbs second-generation complex (HG-II), the structural modification of the benzylidene ligand is a useful strategy. This paper reports the effect of a chalcogen atom placed at the end of the benzylidene group on the catalytic properties of HG-II derivatives, using complexes with a thioether or ether component in the benzylidene ligand (ortho-Me-E-(CH2)2O-styrene; E = S, O). Nuclear magnetic resonance and X-ray crystallographic analyses of the complex with a thioether moiety (E = S) proved the (O,S)-bidentate and trans-dichlorido coordination for the complex. A stoichiometric ligand exchange between HG-II and the benzylidene ligand (E = S) produced the corresponding complex with an 86% yield, confirming higher stability of the complex (E = S) than that of HG-II. Despite the bidentate chelation, the complex (E = S) exhibited OM catalytic activity, indicating the exchangeability of the S-chelating ligand with an olefinic substrate. The green solution color, a characteristic of HG-II derivatives, was retained after the complex (E = S)-mediated OM reactions, indicating high catalyst durability. Conversely, the complex (E = O) rapidly initiated OM reactions; however, it showed low catalyst durability. In the OM reactions conducted in the presence of methanol, the complex (E = S) exhibited higher yields than the complex (E = O) and HG-II: the S-coordination increased the catalyst tolerance to methanol. A coordinative atom (such as sulfur) placed at the terminal of the benzylidene ligand can precisely regulate the reactivity of HG-II derivatives.

Self-Supported Polymeric Ruthenium Complexes as Olefin Metathesis Catalysts in Synthesis of Heterocyclic Compounds

New ruthenium olefin metathesis catalysts containing N-heterocyclic carbene (NHC) connected by a linker tether to a benzylidene ligand were studied. Such obtained self-chelated Hoveyda–Grubbs type complexes existed in the form of an organometallic polymer but could still catalyze olefin metathesis after being dissolved in an organic solvent. Although these polymeric catalysts exhibited a slightly lower activity compared to structurally related nonpolymeric catalysts, they were successfully used in a number of ring-closing metathesis reactions leading to a variety of heterocyclic compounds, including biologically and pharmacologically related analogues of cathepsin K inhibitor and sildenafil (Viagra™). In the last case, a good solubility of a polymeric catalyst in toluene allowed the separation of the product from the catalyst via simple filtration.

Fast Initiating Furan-Containing Hoveyda-Type Complexes: Synthesis and Applications in Metathesis Reactions

Two new ruthenium complexes with chelating-ether benzylidene ligands bearing a furan moiety were synthesized and characterized, including X-ray crystallography. They initiated fast, also at 0 °C, and were found to be highly active in a variety of ring-closing, ene-yne, and cross-metathesis reactions, including an active pharmaceutical ingredient (API) model, which makes them good candidates for the transformation of complex polyfunctional compounds that require mild reaction conditions.

Synthesis of highly stable dual-site immobilized ruthenium olefin metathesis catalyst without ru leaching

The tri-block copolymer is used as a carrier to simultaneously immobilize the N-heterocyclic and benzylidene ligands precursor of the Ru-based catalyst to form a dual-site immobilized catalyst. The dual-site immobilized catalyst can catalyze ring-opening metathesis polymerization, ring-closing metathesis and self-metathesis. The dual-site immobilized catalyst shows good heterogeneity in dichloromethane, which simplifies the purification of product and recovery of catalyst. The dual-site immobilized catalyst exhibits excellent activity and recycling performance. The excellent recyclability can be attributed to the capture of ruthenium by the excess ligands precursor on carrier. Importantly, ruthenium residues are not detected in product.

Preparation of Ruthenium Olefin Metathesis Catalysts Immobilized on MOF, SBA-15, and 13X for Probing Heterogeneous Boomerang Effect

Promoted by homogeneous Ru-benzylidene complexes, the olefin metathesis reaction is a powerful methodology for C-C double bonds formation that can find a number of applications in green chemical production. A set of heterogeneous olefin metathesis pre-catalysts composed of ammonium-tagged Ru-benzylidene complexes 4 (commercial FixCat™ catalyst) and 6 (in-house made) immobilized on solid supports such as 13X zeolite, metal-organic framework (MOF), and SBA-15 silica were obtained and tested in catalysis. These hybrid materials were doped with various amounts of ammonium-tagged styrene derivative 5—a precursor of a spare benzylidene ligand—in order to enhance pre-catalyst regeneration via the so-called release-return “boomerang effect”. Although this effect was for the first time observed inside the solid support, we discovered that non-doped systems gave better results in terms of the resulting turnover number (TON) values, and the most productive were hybrid catalysts composed of 4@MOF, 4@SBA-15, and 6@SBA-15.

A Gentler Touch: Synthesis of Modern Ruthenium Olefin Metathesis Catalysts Sustained by Mechanical Force

AbstractMechanochemical synthesis of nine contemporary ruthenium catalysts used for olefin metathesis is described, being the first reported example of formation of Ru carbene organometallic complexes in solid state. Three key organometallic transformations commonly used in the synthesis of the second and third generations of Ru catalysts in solution—phosphine ligand (PCy3) exchange with in situ formed N‐heterocyclic carbene (NHC) ligand, PCy3 to pyridine ligand replacement, and benzylidene ligands interchange—were proved to work under mechanochemical conditions, affording the targets in high purity. Mechanochemical approach not only requires less amounts of organic solvent (null for synthesis, only for purification) and is scalable, but also allows for transformations that were reported impossible in the solution phase.

Promising Catalytic Processes of Dicyclopentadiene Metathesis Polymerization to Obtain a New Class of Polymeric and Polymer–Composite Materials

A lineup of highly efficient ruthenium catalysts with N-containing substituents in the benzylidene ligand is developed that differ in the rate of initiation of dicyclopentadiene metathesis polymerization. The choice of the optimal catalyst makes it possible to control the lifetime of the monomer–catalyst reaction mixture in a wide range, which makes the use of various technologies effective for the production of polymer and composite materials. The new catalysts have been used to design a series of innovative polymer and polymer-composite materials with a polymer matrix based on a finished monomer, dicyclopentadiene, which is a raw material of the petrochemical industry. The polymeric materials are distinguished by a unique combination of high mechanical properties and good thermal stability in a wide temperature range (from –60 to +320°C), which allows their use in various climatic zones. Composites with a matrix based on polydicyclopentadiene are not inferior to commercially available counterparts based on epoxy and polyester resins and even surpass them in a number of parameters.

Integrating Activity with Accessibility in Olefin Metathesis: An Unprecedentedly Reactive Ruthenium-Indenylidene Catalyst.

Access to leading olefin metathesis catalysts, including the Grubbs, Hoveyda, and Grela catalysts, ultimately rests on the nonscaleable transfer of a benzylidene ligand from an unstable, impure aryldiazomethane. The indenylidene ligand can be reliably installed, but to date yields much less reactive catalysts. A fast-initiating, dimeric indenylidene complex (Ru-1) is reported, which reconciles high activity with scaleable synthesis. Each Ru center in Ru-1 is stabilized by a state-of-the-art cyclic alkyl amino carbene (CAAC, C1) and a bridging chloride donor: the lability of the latter elevates the reactivity of Ru-1 to a level previously attainable only with benzylidene derivatives. Evaluation of initiation rate constants reveals that Ru-1 initiates >250× faster than indenylidene catalyst M2 (RuCl2(H2IMes)(PCy3)(Ind)), and 65× faster than UC (RuCl2(C1)2(Ind)). The slow initiation previously regarded as characteristic of indenylidene catalysts is hence due to low ligand lability, not inherently slow cycloaddition at the Ru=CRR' site. In macrocyclization and "ethenolysis" of methyl oleate (i.e., transformation into α-olefins via cross-metathesis with C2H4), Ru-1 is comparable or superior to the corresponding, breakthrough CAAC-benzylidene catalyst. In ethenolysis, Ru-1 is 5× more robust to standard-grade (99.9%) C2H4 than the top-performing catalyst, probably reflecting steric protection at the quaternary CAAC carbon.

Carbamato-benzylidene ruthenium chelates – Synthesis, structure and catalytic activity in olefin metathesis

New carbamato-κN-benzylidene ruthenium chelates were synthesized from the first [RuCl2(PCy3)2(=CHPh)] and second [RuCl2(SIMes)(PCy3)(=CHPh)] generation Grubbs catalysts by metathetic exchange of benzylidene ligand for tert-butyl (2-vinylphenyl)carbamates bearing benzylidene ligand substituted in the position para to carbamato functionality with methyl or trifluoromethyl group. In all metathetical transformations tested, i.e. in ROMP of cycloocta-1,5-diene, RCM of diethyl diallylmalonate and diethyl 2-allyl-2-(2-methylallyl)malonate and cross-metathesis of allylbenzene with Z-1,4-diacetoxybut-2-ene, the complexes behave like latent catalysts. Complexes remain completely inactive until they are activated by the addition of ethereal solution of HCl. The presence of the electron-withdrawing group results in a slight increase in the catalytic activity of the activated form of the catalyst relative to a similar form of the unsubstituted complex or the least active complex carrying the electron donating group.

Synthesis and dynamic behaviour of a dimeric ruthenium benzylidene complex bearing a truncated N-heterocyclic carbene ligand

Described herein is the reaction of the first-generation Grubbs catalyst RuCl2(PCy3)2(=CHPh) (GI) with free IMe4 (1,3,4,5-tetramethylimidazol-2-ylidene), in which the N-mesityl groups commonly present in Ru-NHC metathesis catalysts are truncated to N-Me (NHC = N-heterocyclic carbene). Treatment of GI with IMe4 (1–2.1 equiv) effects displacement of both PCy3 ligands, but does not terminate at the mono-ruthenium species RuCl2(IMe4)2(=CHPh) Ru-3. Instead, dimerization occurs to afford [Ru2(μ-Cl)3(IMe4)4(=CHPh)2]Cl Ru-4, the structure of which was confirmed by crystallographic analysis. A molecular dynamics study of Ru-4 indicated rapid rotation of both the NHC and the benzylidene ligands, accounting for the observation of multiple benzylidene signals in the solution 1H NMR spectrum of Ru-4.

Syntheses and characterization of molecular weight enlarged olefin metathesis pre-catalysts

Abstract This study was aimed at developing a synthetic strategy of gradual increase in the steric bulk of ruthenium-based olefin metathesis pre-catalysts for organic solvent nanofiltration (OSN) processes. A series of five enlarged second-generation Hoveyda type pre-catalysts was prepared and characterized. The structural modifications were performed on the benzylidene ligand of an unmodified Hoveyda (II) pre-catalyst. The catalytic activity of the catalysts was evaluated in a model reaction of ring closing metathesis (RCM). All enlarged catalysts showed good stabilities and activities comparable to those of the unmodified Hoveyda II pre-catalyst. Cross-flow nanofiltration of these catalysts exhibited very high retentions (up to 98.5%) confirming the potential of structural modifications coupled with OSN for efficient catalysts separation.

Non covalent immobilization of pyrene-tagged ruthenium complexes onto graphene surfaces for recycling in olefin metathesis reactions

Synthesis of Hoveyda-type ruthenium complexes, modified by pyrene tags on the NHC ligand and/or the benzylidene moiety, is described. Thanks to non-covalent π-π interactions these new complexes were immobilized on carbon supports [reduced graphene oxide (rGO) or graphene] and their activity and recoverability for metatheses reactions have been studied. A SIPr-based complex possessing the pyrene function on the benzylidene ligand (C2) delivered the best results for the ring closing metathesis of diethyldiallyl malonate as benchmark reaction. The presence of additional pyrene-functionalized styrenyl-ether as ligand to the rGO-supported catalyst (C2/L@rGO) noticeably improved the recycling procedure allowing supplementary efficient catalytic runs. This may be due either to a facilitated boomerang effect or to a gradual release of the active species in solution. Finally, catalyst C2/L@rGO was proven to be successfully used to promote metathesis reactions in a multisubstrate procedure, the same supported-catalyst batch being successively engaged to transform three different substrates, in diene and ene-yne RCM reactions.

Evaluation of DNA binding, DNA cleavage, protein binding, radical scavenging and in vitro cytotoxic activities of ruthenium(II) complexes containing 2,4-dihydroxy benzylidene ligands

The new ruthenium(II) complexes with hydrazone ligands, 4-Methyl-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL1), 4-Methoxy-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL2), 4-Bromo-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL3), were synthesized and characterized by various spectro analytical techniques. The molecular structures of the ligands were confirmed by single crystal X-ray diffraction technique. The DNA binding studies of the ligands and complexes were examined by absorption, fluorescence, viscosity and cyclic voltammetry methods. The results indicated that the ligands and complexes could interact with calf thymus DNA (CT-DNA) through intercalation. The DNA cleavage activity of the complexes was evaluated by gel electrophoresis assay, which revealed that the complexes are good DNA cleaving agents. The binding interaction of the ligands and complexes with bovine serum albumin (BSA) was investigated using fluorescence spectroscopic method. Antioxidant studies showed that the complexes have a strong radical scavenging properties. Further, the cytotoxic effect of the complexes examined on cancerous cell lines showed that the complexes exhibit significant anticancer activity.

Remarkable Ability of the Benzylidene Ligand To Control Initiation of Hoveyda–Grubbs Metathesis Catalysts

The structure of the chelating benzylidene ligand offers the unique ability to control the initiation of Hoveyda–Grubbs metathesis catalysts. Apart from steric and electronic effects acting on the step involving opening of the chelate ring, changes related to the following ligand-exchange process may also play a critical role. Our mechanistic model reveals that ligands substituted at the 6-position of the benzylidene ring enter the metathesis cycle in a nonoptimal chelating conformation, and thus the coordination number of the ruthenium center transiently increases to six (associative mechanism). In effect, the synthesis and initiation of the catalysts becomes difficult, and the energy barrier of the ligand-exchange process is controlled by the structure of the coordinating OR group. Moreover, we explain how isomeric naphthalene ligands affect the catalytic performance by an indivisible combination of steric and π-electron delocalization effects.

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

Reactions are described of the second-generation Hoveyda catalyst HII with amines, pyridine, and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), in the presence and absence of olefin substrates. These nitrogen bases have a profoundly negative impact on metathesis yields, but in most cases, they are innocuous toward the precatalyst. HII adducts were formed by primary and secondary amines (n-butylamine, sec-butylamine, benzylamine, pyrrolidine, morpholine), pyridine, and DBU at room temperature. No reaction was evident for NEt3, even at 60 °C. On longer reaction at RT, unencumbered primary amines abstract the benzylidene ligand from HII. With 10 equiv of NH2nBu, this process was complete in 12 h, affording NHnBu(CH2Ar) (Ar = o-C6H4–OiPr) and [RuCl(H2IMes)(NH2nBu)4]Cl. For benzylamine, benzylidene abstraction occurred over days at RT. No such reaction was observed for sec-butylamine, secondary amines, NEt3, pyridine, or DBU. All of these bases, however, strongly inhibited metathesis of styrene by HII, with a gener...

The Key Role of the Nonchelating Conformation of the Benzylidene Ligand on the Formation and Initiation of Hoveyda-Grubbs Metathesis Catalysts.

Experimental studies of Hoveyda-Grubbs metathesis catalysts reveal important consequences of substitution at the 6-position of the chelating benzylidene ligand. The structural modification varies conformational preferences of the ligand that affects its exchange due to the interaction of the coordinating site with the ruthenium center. As a consequence, when typical S-chelated systems are formed as kinetic trans-Cl2 products, for 6-substituted benzylidenes the preference is altered toward direct formation of thermodynamic cis-Cl2 isomers. Activity data and reactions with tricyclohexylphosphine (PCy3 ) support also a similar scenario for O-chelated complexes, which display fast trans-Cl2 ⇄cis-Cl2 equilibrium observed by NMR EXSY studies. The presented conformational model reveals that catalysts, which cannot adopt the optimal nonchelating conformation of benzylidene ligand, initiate through a high-energy associative mechanism.

ChemInform Abstract: Evolution of Catalytic Stereoselective Olefin Metathesis: From Ancillary Transformation to Purveyor of Stereochemical Identity

AbstractReview: [121 refs.

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.

Evolution of catalytic stereoselective olefin metathesis: from ancillary transformation to purveyor of stereochemical identity.

There have been numerous significant advances in catalytic olefin metathesis (OM) during the past two decades. Such progress has transformed this important set of reactions to strategically pivotal processes that generate stereochemical identity while delivering molecules that cannot be easily prepared by alternative routes. In this Perspective, an analysis of the origin of the inception of bidentate benzylidene ligands for Ru-based OM catalysts is first presented. This is followed by an overview of the intellectual basis that culminated in the development of Mo-based diolates and stereogenic-at-Ru complexes for enantioselective OM. The principles accrued from the study of the latter Ru carbenes and Mo alkylidenes and utilized in the design of stereogenic-at-Mo, -W, and -Ru species applicable to enantioselective and Z-selective OM are then discussed. The influence of the recently introduced catalytic OM protocols on the design of synthesis routes leading to complex organic molecules is probed. The impact of a better understanding of the mechanistic nuances of OM toward the discovery of stereoselective catalysts is reviewed as well.

Ring-Opening Metathesis Polymerization with the Second Generation Hoveyda–Grubbs Catalyst: An Efficient Approach toward High-Purity Functionalized Macrocyclic Oligo(cyclooctene)s

Herein, we present a facile and general strategy to prepare functionalized macrocyclic oligo(cyclooctene)s (cOCOEs) in high purity and high yield by exploiting the ring-opening metathesis polymerization (ROMP) intramolecular backbiting process with the commercially available second generation Hoveyda-Grubbs (HG2) catalyst. In the first instance, ROMP of 5-acetyloxycyclooct-1-ene (ACOE) followed by efficient quenching and removal of the catalyst using an isocyanide derivative afforded macrocyclic oligo(5-acetyloxycyclooct-1-ene) (cOACOE) in high yield (95%), with a weight-average molecular weight (Mw) of 1.6 kDa and polydispersity index (PDI) of 1.6, as determined by gel permeation chromatography (GPC). The structure and purity of the macrocycles were confirmed by NMR spectroscopy and elemental analysis, which indicated the complete absence of end-groups. This was further supported by GPC-matrix assisted laser desorption ionization time-of-flight mass spectroscopy (GPC-MALDI ToF MS), which revealed the exclusive formation of macrocyclic derivatives composed of up to 45 repeat units. Complete removal of residual ruthenium from the macrocycles was confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The same methodology was subsequently extended to the ROMP of 5-bromocyclooct-1-ene and 1,5-cyclooctadiene to prepare their macrocyclic derivatives, which were further derivatized to produce a library of functionalized macrocyclic oligo(cyclooctene)s. A comparative study using the second and third generation Grubbs catalysts in place of the HG2 catalyst for the polymerization of ACOE provided macrocycles contaminated with linear species, thus indicating that the bidendate benzylidene ligand of the Hoveyda-Grubbs catalyst plays an important role in the observed product distributions.