Synthesis and Evaluation of Ruthenium 2‐Alkyl‐6‐mercaptophenolate Catalysts for Olefin Metathesis

A series of ruthenium carbene catalysts containing 2‐sulfidophenolate bidentate ligand with an ortho‐substituent next to the oxygen atom were synthesized. The molecular structure of ruthenium carbene complex containing 2‐isopropyl‐6‐sulfidophenolate ligand was confirmed through single crystal X‐ray diffraction. An oxygen atom can be found in the opposite position of the N‐heterocyclic carbene (NHC) based on the steric hindrance and strong trans‐effects of the NHC ligand. The ruthenium carbene catalyst can catalyze ring‐opening metathesis polymerization (ROMP) reaction of norbornene with high activity and Z‐selectivity and cross metathesis (CM) reactions of terminal alkenes with (Z)‐but‐2‐ene‐1,4‐diol to give Z‐olefin products (Z/E ratios, 70:30–89:11) in low yields (13%–38%). When AlCl₃ was added into the CM reactions, yields (51%–88%) were considerably improved and process becomes highly selective for E‐olefin products (E/Z ratios, 79:21–96:4). Similar to other ruthenium carbene catalysts, these new complexes can tolerate different functional groups.     

ESIMS Studies and Calculations on Alkali‐Metal Adduct Ions of Ruthenium Olefin Metathesis Catalysts and Their Catalytic Activity in Metathesis Reactions

Electrospray ionization mass spectrometry (ESIMS) and subsequent tandem mass spectrometry (MS/MS) analyses were used to study some important metathesis reactions with the first‐generation ruthenium catalyst 1 , focusing on the ruthenium complex intermediates in the catalytic cycle. In situ cationization with alkali cations (Li⁺, Na⁺, K⁺, and Cs⁺) using a microreactor coupled directly to the ESI ion source allowed mass spectrometric detection and characterization of the ruthenium species present in solution and particularly the catalytically active monophosphine–ruthenium intermediates present in equilibrium with the respective bisphosphine–ruthenium species in solution. Moreover, the intrinsic catalytic activity of the cationized monophosphine–ruthenium complex 1 a ?K⁺ was directly demonstrated by gas‐phase reactions with 1‐butene or ethene to give the propylidene Ru species 3 a ?K⁺ and the methylidene Ru species 4 a ?K⁺, respectively. Ring‐closing metathesis (RCM) reactions of 1,6‐heptadiene ( 5 ), 1,7‐octadiene ( 6 ) and 1,8‐nonadiene ( 7 ) were studied in the presence of KCl and the ruthenium alkylidene intermediates 8 , 9 , and 10 , respectively, were detected as cationized monophosphine and bisphosphine ruthenium complexes. Acyclic diene metathesis (ADMET) polymerization of 1,9‐decadiene ( 14 ) and ring‐opening metathesis polymerization (ROMP) of cyclooctene ( 18 ) were studied analogously, and the expected ruthenium alkylidene intermediates were directly intercepted from reaction solution and characterized unambiguously by their isotopic patterns and ESIMS/MS. ADMET polymerization was not observed for 1,5‐hexadiene ( 22 ), but the formation of the intramolecularly stabilized monophosphine ruthenium complex 23 a was seen. The ratio of the signal intensities of the respective with potassium cationized monophosphine and bisphosphine alkylidene Ru species varied from [I _4a ]/[I ₄ ]=0.02 to [I _23a ]/[I ₂₃ ]=10.2 and proved to be a sensitive and quantitative probe for intramolecular π‐complex formation of the monophosphine–ruthenium species and of double bonds in the alkylidene chain. MS/MS spectra revealed the intrinsic metathesis catalytic activity of the potassium adduct ions of the ruthenium alkylidene intermediates 8 a , 9 a , 10 a , 15 a , and 19 a , but not 23 a by elimination of the respective cycloalkene in the second step of RCM. Computations were performed to provide information about the structures of the alkali metal adduct ions of catalyst 1 and the influence of the alkali metal ions on the energy profile in the catalytic cycle of the metathesis reaction.     

Highly Active Carbene Ruthenium Catalyst for Metathesis of 1-Hexene

A new carbene ruthenium complex, 1,3-bis（2,6-dimethylphenyl）-4,5-dihydroimidazol-2-ylidene）（PPh3）Cl2-Ru=CHPh, was synthesized and used as catalyst for the metathesis of 1-hexene. The resulting complex exhibited very high catalytic activity whose TOF is up to 6680 h^-1. However, at the same time significant olefin isomerization was observed and could be surpressed by changing reaction conditions, such as temperature, time, alkene/Ru molar ratio and solvent.     

A Thermo‐ and Photo‐Switchable Ruthenium Initiator For Olefin Metathesis

A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X‐ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring‐closing and ring‐opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.     

Synthesis and Catalytic Activity of a Two-core Ruthenium Carbene Complex: a Unique Catalyst for Ring Closing Metathesis Reaction

The reaction of a ruthenium carbide complex RuCl2(C:)(PCy3)2 with [H(Et2O)x]+[BF4]– at a molar ratio of 1:2 produced a two-core ruthenium carbene complex, {[RuCl(=CHPCy3)(PCy3)]2(μ-Cl)3}+·[BF4]–, in the form of a yellow-green crystalline solid in a yield of 94%. This two-core ruthenium complex is a selective catalyst for ring closing metathesis of unsubstituted terminal dienes. More importantly, no isomerized byproduct was observed for N-substrates when the two-core ruthenium complex was used as the catalyst at an elevated temperature(137 °C), indicating that the complex is a chemo-selective catalyst for ring closing metathesis reactions.     

Poly(fluoroalkyl acrylate)-bound ruthenium carbene complex: a fluorous and recyclable catalyst for ring-closing olefin metathesis

The synthesis of a fluorous olefin metathesis catalyst derived from the Grubbs second-generation ruthenium carbene complex is described. The air stable fluorous polymer-bound ruthenium carbene complex 1 shows high reactivity in effecting the ring-closing metathesis of a broad spectrum of diene and enyne substrates leading to the formation of di-, tri-, and tetrasubstituted cyclic olefins in minimally fluorous solvent systems (PhCF3/CH2Cl2, 1:9-1:49 v/v). The catalyst can be readily separated from the reaction mixture by fluorous extraction with FC-72 and repeatedly reused. The practical advantage offered by the fluorous catalyst is demonstrated by its sequential use in up to five different metathesis reactions.     

Alkyne gem‐Hydrogenation: Formation of Pianostool Ruthenium Carbene Complexes and Analysis of Their Chemical Character

Parahydrogen (p‐H₂) induced polarization (PHIP) NMR spectroscopy showed that [Cp^XRu] complexes with greatly different electronic properties invariably engage propargyl alcohol derivatives into gem‐hydrogenation with formation of pianostool ruthenium carbenes; in so doing, less electron rich Cp^X rings lower the barriers, stabilize the resulting complexes and hence provide opportunities for harnessing genuine carbene reactivity. The chemical character of the resulting ruthenium complexes was studied by DFT‐assisted analysis of the chemical shift tensors determined by solid‐state ¹³C NMR spectroscopy. The combined experimental and computational data draw the portrait of a family of ruthenium carbenes that amalgamate purely electrophilic behavior with characteristics more befitting metathesis‐active Grubbs‐type catalysts.     

Cationic Bis‐N‐Heterocyclic Carbene (NHC) Ruthenium Complex: Structure and Application as Latent Catalyst in Olefin Metathesis

An unexpected cationic bis‐N‐heterocyclic carbene (NHC) benzylidene ether based ruthenium complex ( 2 a ) was prepared through the double incorporation of an unsymmetrical unsaturated N‐heterocyclic carbene (U₂‐NHC) ligand that bore an N‐substituted cyclododecyl side chain. The isolation and full characterization (including X‐ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring‐closing metathesis, which could be “switched on” under acidic conditions.     

In a Quest for Selectivity Paired with Activity: A Ruthenium Olefin Metathesis Catalyst Bearing an Unsymmetrical Phenanthrene-Based N-Heterocyclic Carbene

Robust, selective, and stable in the presence of ethylene, ruthenium olefin metathesis pre-catalyst, {[3-benzyl-1-(10-phenyl-9-phenanthryl)]-2-imidazolidinylidene}dichloro(o-isopropoxyphenylmethylene)ruthenium(II), Ru-3 , bearing an unsymetrical N-heterocyclic carbene (uNHC) ligand, has been synthesized. The initiation rate of Ru-3 was examined by ring-closing metathesis and cross-metathesis reactions with a broad spectrum of olefins, showing an unprecendented selectivity. It was also tested in industrially relevant ethenolysis reactions of olefinic substrates from renewable feedstock with very good yields and selectivities.     

Toward the synthesis of amphidinolide P: optimization of a model ene–yne metathesis fragment coupling

Ene–yne cross metathesis was assessed for use as a key fragment coupling in a planned total synthesis of amphidinolide P. A terminal alkyne containing a β,γ-epoxide was synthesized and employed as the alkyne partner in an intermolecular ene–yne metathesis. In the alkene substrate, optimal functionality and reaction conditions were determined. An unprotected allyl alcohol was found to be critical for both high yield and high E-selectivity. Fewer equivalents of the alkene resulted in incomplete reaction and side reactions consumed the terminal alkyne. The best ruthenium carbene precatalysts were found to be the Hoveyda–Grubbs carbene complexes.     

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.     

Comparing Grubbs‐, Werner‐, and Hofmann‐Type (Carbene)ruthenium Complexes: The Key Role of Pre‐Equilibria for Olefin Metathesis

A gas‐phase comparison of intrinsic olefin metathesis rates for (carbene)ruthenium complexes by means of electrospray‐ionization tandem mass spectrometry reveals a reversal of the reactivity trends observed in solution. The solution‐phase ordering of reactivity is accordingly attributed to a more favorable pre‐equilibrium, producing the metathesis‐active species in the case of the Hofmann‐ and Werner‐type complexes relative to those of the Grubbs type.     

Enolesters as chain end-functionalizing agents for the living ring opening metathesis polymerization

Functional enolethers have previously been used to introduce functional end groups at the chain end of ruthenium carbene complex initiated living ring opening metathesis polymers. Here, we investigated whether the weaker π-donating enolesters could equally be used in regio selective reactions with ruthenium carbene complexes and thus as polymer end-functionalization reagents. Enolesters such as vinyl acetate, butenyl acetate, 3-(4-(tert-butoxy)phenyl)propenyl acetate and 6-(((benzyloxy)carbonyl)amino)hex-1-en-1-yl acetate were used as living ROMP terminating agents. All gave the expected end groups proving that enolesters are synthetically easily accessible targets for living ROMP end-functionalization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2983–2990     

Studies on synthesis of quinonylidene Hoveyda‐type complexes

In a quest of redox‐switchable metathesis catalysts we attempted synthesis of ruthenium quinonylidene complexes using two synthetic pathways. First, Hoveyda‐type complexes bearing chelating benzylidene and naphthylidene ligands substituted with two alkoxy/hydroxy groups were synthesized and characterized. The catalysts were tested in model ring‐closing metathesis reactions, and displayed interesting correlations between structure and catalytic activity. Unfortunately, numerous attempts at oxidation of the complexes to derivatives of benzo‐ and naphthoquinone were unsuccessful. However, the second approach, using exchange reaction of ruthenium precursor with vinylquinone ligand, gave a transient unstable product observed with ¹H NMR. The experimental data suggest that conjugation of electron‐deficient quinones to the ruthenium centre results in intrinsically unstable species, which undergo secondary reactions under ambient conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Highly Efficient Ruthenium‐Based Catalytic Systems for the Controlled Free‐Radical Polymerization of Vinyl Monomers

A new set of ruthenium complexes such as 1 and 2 (the Grubbs ruthenium–carbene complex) has been shown to mediate the controlled atom‐transfer radical polymerization (ATRP) of vinyl monomers with exceptional efficiency. Furthermore, there is a striking parallelism between the catalytic activity of these compounds in olefin metathesis and in ATRP.     

A Light‐Activated Olefin Metathesis Catalyst Equipped with a Chromatic Orthogonal Self‐Destruct Function

A sulfur‐chelated photolatent ruthenium olefin metathesis catalyst has been equipped with supersilyl protecting groups on the N‐heterocyclic carbene ligand. The silyl groups function as an irreversible chromatic kill switch, thus decomposing the catalyst when it is irradiated with 254 nm UV light. Therefore, different types of olefin metathesis reactions may be started by irradiation with 350 nm UV light and prevented by irradiation with shorter wavelengths. The possibility to induce and impede catalysis just by using light of different frequencies opens the pathway for stereolithographic applications and novel light‐guided chemical sequences.     

Tandem enyne metathesis-Diels-Alder reaction for construction of natural product frameworks

Enynes connected through aromatic rings are used as substrates for metathesis reactions. The reactivity of three ruthenium carbene complexes is compared. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels-Alder process. Some domino RCM-Diels-Alder reactions are performed, suggesting a possible beneficial effect of the ruthenium catalyst in the cycloaddition process. Other examples require Lewis acid cocatalyst. When applied to aromatic ynamines or enamines, a new synthesis of vinylindoles is achieved. Monitorization of several metathesis reactions with NMR shows the different behavior for ruthenium catalysts. New carbenic species are detected in some reactions with an important dependence on the solvent used.     

Z‐Selective Cross Metathesis with Ruthenium Catalysts: Synthetic Applications and Mechanistic Implications

Olefin cross metathesis is a particularly powerful transformation that has been exploited extensively for the formation of complex products. Until recently, however, constructing Z‐olefins using this methodology was not possible. With the discovery and development of three families of ruthenium‐based Z‐selective catalysts, the formation of Z‐olefins using metathesis is now not only possible but becoming increasingly prevalent in the literature. In particular, ruthenium complexes containing cyclometalated NHC architectures developed in our group have been shown to catalyze various cross metathesis reactions with high activity and, in most cases, near perfect selectivity for the Z‐isomer. The types of cross metathesis reactions investigated thus far are presented here and explored in depth.     

A rapid and simple cleanup procedure for metathesis reactions

[structure: see text]. A new method for easy removal of ruthenium from metathesis reactions by using a polar isocyanide is reported. This protocol removed most ruthenium byproducts from a variety of synthetically useful metatheses. Moreover, the isocyanide-promoted carbene insertion results in rapid destruction of carbene reactivity, demonstrated in the commonly used first- and second-generation Grubbs' carbenes.     

Improved molecular weight control in ring‐opening metathesis polymerization reactions in organic and aqueous media using N‐heterocyclic carbene–ruthenium arene/alkyne catalyst systems

A binary catalytic system, RuCl₂(N‐heterocyclic carbene)(p‐cymene)/alkyne, was developed for improved molecular weight control in ring‐opening metathesis polymerization (ROMP) reactions of norbornene derivatives in organic and aqueous media. Monometallic ruthenium arene compounds were activated using aryl and aliphatic terminal alkynes to form highly active metathesis species. The effects of alkyne structure and concentration on the overall catalytic activity were systematically investigated. The catalytic activity of the metathesis active species can be tuned by varying alkyne substituents. Also, the initiation rate of the ROMP reaction can be tuned by increasing the alkyne‐to‐Ru ratio. ROMP polymers with a wide range of molecular weights (91–832 kDa) were isolated in organic media, whereas polymers with a molecular weight range of 110–280 kDa with average particle sizes of 150–250 nm were isolated in aqueous media. Copyright © 2016 John Wiley & Sons, Ltd.