Grubbs Catalyst Research Articles

A Regulable Internal Cavity inside a Resorcinarene-Based Hemicarcerand.

Covalent organic capsules, such as carcerands and hemicarcerands, are an interesting class of molecular hosts. These container molecules have confined spaces capable of hosting small molecules, although the fact that the size of the inner cavities cannot be changed substantially limits the scope of their applications. The title covalently linked container was produced by metal-directed dimerization of a resorcinarene-based cavitand having four 2,2'-bipyridyl arms on the wide rim followed by olefin metathesis at the vertices of the resulting capsule with a second-generation Grubbs catalyst. The covalently linked bipyridyl arms permit expansion of the inner cavity by demetalation. This structural change influences the molecular recognition properties; the metal-coordinated capsule recognizes only 4,4'-diacetoxybiphenyl, whereas the metal-free counterpart can encapsulate not only 4,4'-diacetoxybiphenyl, but also 2,5-disubstituted-1,4-bis(4-acetoxyphenylethynyl)benzene, which is 9.4 Å longer than the former guest. Molecular mechanics calculations predict that the capsule expands the internal cavity to encapsulate the long guest by unfolding the folded conformation of the alkyl chains, which demonstrates the flexible and regulable nature of the cavity. Guest competition experiments show that the preferred guest can be switched by metalation and demetalation. This external-stimuli-responsive guest exchange can be utilized for the development of functional supramolecular systems controlling the uptake, transport, and release of chemicals.

Acrylate Esters by Ethenolysis of Maleate Esters with Ru Metathesis Catalysts: an HTE and a Technoeconomic Study

AbstractA high throughput experimentation (HTE) study identified active Ru metathesis catalysts and reaction conditions for the ethenolysis of maleate esters to the respective acrylate esters. Catalysts were tested at various loadings (75–10’000 ppm) and temperatures (30–60 °C) with maleate esters dissolved in toluene (up to ca. 44 wt‐%) or neat and at variable partial pressures of ethylene (0.2–10 bar). Ruthenium catalysts containing a PCy3 ligand, such as 1st or 2nd generation Grubbs catalysts, as well as the state‐of‐the‐art catalysts containing cyclic alkyl amino carbene (CAAC) ligands, are generally inferior to Hoveyda–Grubbs 2nd generation catalyst in ethenolysis of maleates. Productive turnover numbers could exceed 1900 if the ethenolysis reaction is performed at low ethylene pressure (0.2–3 bar) and reach 5200 when a polymeric phenol additive was used. Such catalytic performance falls well within the window practiced in industry. Moreover, a crude technoeconomic analysis finds similar production cost for the ethenolysis route and conventional technology, that is, propene oxidation followed by esterification, justifying research to further improve the ethenolysis route.

One-step Synthesis of End-Functionalized Hydrogenated Nitrile-Butadiene Rubber by Combining the Functional Metathesis with Hydrogenation.

End‐functionalized hydrogenated polymers obtained from nitrile‐butadiene rubber (NBR) yield new materials with suitable properties for a number of applications as sealing material and adhesives. We investigated the one‐step synthesis of ester end‐functionalized hydrogenated nitrile‐butadiene rubber (EF‐HNBR) by combining the functional metathesis with the hydrogenation of NBR in the presence of the 2nd generation Grubbs catalyst and a functionalized olefin as a chain transfer agent (CTA). We established the operating conditions for the effective production of saturated functional polymers with a high degree of hydrogenation, high chemo‐selectivity and moderate molecular weight. The structures of the products were confirmed by FT‐IR and 1H‐NMR spectroscopy, rubber molecular weight, and distribution determined by using gel permeation chromatography (GPC); their thermal properties were determined by thermo‐gravimetric analysis (TGA) and different scanning calorimetry (DSC).

Synthesis of Conjugated Polyenynes with Alternating Six- and Five-Membered Rings via β-Selective Cascade Metathesis and Metallotropy Polymerization.

Cascade metathesis and metallotropy (M&M) polymerization, which involves sequential olefin metathesis and metallotropic 1,3-shift reactions specifically from multiyne monomers, is the only method reported so far to prepare conjugated polyenynes via the chain-growth mechanism. Using this method, various conjugated polyenynes containing cyclopentene units in the backbone could be synthesized via exclusive α-addition by using the third-generation Grubbs catalyst. Herein, we demonstrate the complete switch of regioselectivity toward β-addition using a Ru carbene containing a dithiolate ligand, and thus, synthesized unique conjugated polyenynes having alternating cyclohexene and cyclopentene units in the backbone. Furthermore, detailed in situ NMR studies revealed an interesting phenomenon that the adjacent triple bond strongly chelates to the propagating Ru carbene during the polymerization.

Cationic Bottlebrush Polymers from Quaternary Ammonium Macromonomers by Grafting‐Through Ring‐Opening Metathesis Polymerization

AbstractCationic bottlebrush homopolymers are polymerized using a grafting‐through approach by ring‐opening metathesis polymerization (ROMP) to afford well‐defined polymers. Quaternary ammonium macromonomers (MMs) are prepared by quaternizing tertiary amine MMs synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. The quaternary ammonium MMs undergo ROMP to target molecular weights (Mn = 30 000–100 000 g mol−1) and a low dispersity (Đ = 1.10–1.30). Halide‐ligand exchange between the third generation Grubbs catalyst (G3) and halide counter ions (bromide and iodide ions) of MMs changes the catalyst activity throughout ROMP, causing it to deviate from pseudo‐first order kinetic behavior; however, the polymerization still follows controlled behavior without significant catalyst termination. Increasing steric bulk of the MMs decreases the polymerization rate as well. Amphiphilic block copolymers are synthesized by sequential polymerization of quaternary ammonium MMs and polystyrene (PS) MMs. Using a PS macroinitiator affords block copolymers with lower Đ values as compared to the less active cationic macroinitiator.

Synthesis of high-molecular weight poly(1,1-dimethyl-1-silapentene) by olefin metathesis polymerization in the presence of Grubbs catalysts

Heterochain polycarbosilanes are well-known materials possessed important properties. Some of their applications, such as gas separation membranes, require polymers with high molecular weight that provide good film-forming and mechanical properties. In this research, the synthesis of poly(1,1-dimethyl-1-silapentene) via the ring-opening metathesis polymerization (ROMP) of 1,1-dimethyl-1-silacyclopentene and the acyclic dienes metathesis (ADMET) of diallyldimethylsilane mediated by Ru-carbene Grubbs complexes 1st - 3rd generations as well as Hoveyda-Grubbs 2nd generation catalyst were studied for the first time. High molecular weight poly(1,1-dimethyl-1-silapentene) was synthesized by ROMP of 1,1-dimethyl-1-silacyclopentene. Varying the type and loading catalyst, temperature and monomer concentration, we obtained poly(1,1-dimethyl-1-silapentene) with Mw = 100–143 kDa, which is significantly higher (5–7 times) than that reached previously by olefin metathesis polymerization. The activities of 1,1-dimethyl-1-silacyclopentene and cyclopentene in ROMP were compared using 1H NMR monitoring the conversion of their double bonds. The ADMET polymerization of diallyldimethylsilane led to oligomers with the average polymerization degree not exceeded 4.4.

Efficient Synthesis of Asymmetric Miktoarm Star Polymers.

Asymmetric miktoarm star polymers comprising an unequal number of chemically-distinct blocks connected at a common junction produce unique material properties, yet existing synthetic strategies are beleaguered by complicated reaction schemes that are restricted in both monomer scope and yield. Here, we introduce a new synthetic approach coined "μSTAR" - Miktoarm Synthesis by Termination After Ring-opening metathesis polymerization - that circumvents these traditional synthetic limitations by constructing the block-block junction in a scalable, one-pot process involving (1) grafting-through polymerization of a macromonomer followed by (2) in-situ enyne-mediated termination to install a single mikto-arm with exceptional efficiency. This modular μSTAR platform cleanly generates AB n and A(BA') n miktoarm star polymers with unprecedented versatility in the selection of A and B chemistries as demonstrated using many common polymer building blocks: poly(siloxane), poly(acrylate), poly(methacrylate), poly(ether), poly(ester), and poly(styrene). The average number of B or BA' arms (n) is easily controlled by the molar equivalents of macromonomer relative to Grubbs catalyst in the initial ring-opening metathesis polymerization step. While these materials are characterized by dispersity in n that arises from polymerization statistics, they self-assemble into mesophases that are identical to those predicted for precise miktoarm stars as evidenced by small-angle X-ray scattering experiments and self-consistent field theory simulations. In summary, the μSTAR technique provides a significant boost in design flexibility and synthetic simplicity while retaining the salient phase behavior of precise miktoarm star materials.

Molecular Modeling of Mechanisms of Decomposition of Ruthenium Metathesis Catalysts by Acrylonitrile

We report a computational mechanistic study explaining the low stability of Hoveyda–Grubbs catalyst in the presence of acrylonitrile. We show the atomistic and energetic basis of why recently synth...

Recent Advances in Rare Earth Complexes Containing N-Heterocyclic Carbenes: Synthesis, Reactivity, and Applications in Polymerization

N-heterocyclic carbenes (NHCs) are ubiquitous ancillary ligands employed in metal-catalyzed homogeneous reactions and polymerization reactions. Of significance is the use of NHCs as the supporting ligand in second- and third-generation Grubbs catalysts for their application in olefin metathesis and ring-opening metathesis polymerization. While the applications of transition metal catalysts ligated with NHCs in polymerization chemistry are well-documented, the use of analogous rare earth (Ln = Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) catalysts in this area remains under-developed, despite the unique role of rare earth elements in regio- and stereo-specific (co)polymerization reactions. By using hetero-atom-tethered chelating NHCs and, more recently, the employment of other structurally related NHCs, NHC-ligated Ln complexes have proven to be promising and fruitful catalysts for selective polymerization reactions. This review summarizes the recent developments in the coordination chemistry of Ln complexes containing NHCs and their catalytic performance in polymerization.

Impact of the olefin structure on the catalytic cycle and decomposition rates of Hoveyda-Grubbs metathesis catalysts.

A relatively fast degradation of ruthenium catalysts in the presence of selected olefins, and ethylene in particular, is one of the bottlenecks in their use in metathesis reactions. Here we explore the structure-activity relationships between the rate of degradation of Hoveyda-Grubbs catalysts and the structure of olefins by means of DFT calculations. We show that (Z)-1,2-dichloroethene can't form stable complexes with a 14-electron active complex due to a strong inductive electron withdrawal effect. Hoveyda-Grubbs catalysts can be, however, used to convert (Z)-1,2-dichloroethene to (E)-1,2-dichloroethene due to differences in crucial barriers in the catalytic cycle for E/Z isomers. Hoveyda-Grubbs catalysts in the presence of both isomers of 1,2-dimethoxyethene and 1,2-dichloroethene are predicted to be very stable in the unproductive metathesis, while for monosubstituted olefins the methoxyethene presence gives relatively low barriers for crucial degradation transition states and can readily undergo decomposition.

Derivatives of pyrimidine-2,4,6-triones as components of additives to increase the lubricating properties of motor fuels

One of the important tasks of modern petrochemistry is the development of new additives that can improve the performance of motor fuels. With the expansion of the number of automotive and agricultural machinery and increasing its technical level, the demand for a wider range of petroleum products is increasing and, as well, the requirements for their quality are increasing. As the environmental and operational requirements for motor fuels are constantly increasing, it is necessary to find new, more efficient additives. The paper describes the synthesis of spirocyclic pyrimidine-2,4,6-trionеs by ring-closing metathesis reactions (RCM). This type of transformation is actively used in petrochemical and organic syntheses and allows to obtain compounds that are difficult to synthesize by conventional methods of organic chemistry. RCM conversion was performed using a Grubbs-Hoveyda catalyst in an amount of 5 mol. %. The compounds formed during the reaction were investigated as additives to motor fuels. Studies of the effect of synthesized spiropyrimidine-2,4,6-trione derivatives as additives on the tribological characteristics of ethanol and diesel fuel were evaluated on a four-ball tribometer in terms of critical load. At least three experiments were performed at each load. The error of the experiment was less than 5%. It was found that substances 2c and 2b increase the lubricating properties of ethanol - the critical load to the fuel burr when adding the synthesized compounds increased by 25%. Spiropyrimidine-2,4,6-trione 2b also had a positive effect on the lubricity of diesel fuel and had the effect of increasing the load to burr by 12% at a concentration of 0.032%. Thus, derivatives of spiropyrimidine-2,4,6-triones have proven to be promising compounds for the manufacture of motor fuels.

Mono-telechelic polymers by catalytic living ring-opening metathesis polymerization with second-generation Hoveyda–Grubbs catalyst

Mono-telechelic polymers and triblock copolymers were synthesized by catalytic living ROMP with unstabilized 14e−HG2 catalyst.

Syntheses of polynorbornadienes by ring-opening metathesis polymerizations of symmetric and non-symmetric 2,3-bis(alkoxycarbonyl)norbornadienes and their conversion to half-ester derivatives.

Libraries of polynorbornadienes were synthesized with good yields with a ruthenium-containing 2nd generation Grubbs catalyst by ring-opening metathesis polymerization (ROMP) of a variety of symmetric and non-symmetric 2,3-bis(alkoxycarbonyl)norbornadiene monomer units prepared from the half-esters obtained efficiently by the selective monohydrolysis reactions of symmetric diesters we reported earlier. Among these polymers, the polynorbornadienes with t-butoxycarbonyl groups derived from non-symmetric monomer units were converted to the half-ester derivatives by deprotection with trifluoroacetic acid, yielding amphiphilic polymers. The hydrogenation reactions of the obtained polymers were carried out to yield polymers having saturated structures in the main chains for improvement of the thermal stabilities. All these polymers were characterized by their molecular weights and thermal properties along with the spectroscopic data. Our selective monohydrolysis reactions have been proven to be a versatile tool for production of relatively homogeneous polymer libraries.

Enol Ethers Are Effective Monomers for Ring-Opening Metathesis Polymerization: Synthesis of Degradable and Depolymerizable Poly(2,3-dihydrofuran).

Enol ethers are widely used as quenching reagents for Grubbs catalysts. However, we report the surprisingly effective ring-opening metathesis polymerization (ROMP) of cyclic enol ethers, because the resulting electron-rich ruthenium alkylidene complex remains active toward metathesis of electron-rich olefins, despite its deactivation toward hydrocarbon olefins. We demonstrate the first example of ROMP of cyclic enol ethers, using 2,3-dihydrofuran as the monomer, producing a new type of degradable and depolymerizable poly(enol ether). The polymers exhibited perfect regioregularity, and their molecular weights can be regulated by the loading of Grubbs initiators or by the use of a linear vinyl ether as the chain transfer agent. We also developed protocols to deactivate the catalyst following metathesis of enol ethers and cleave the catalyst off the resulting polymers using H2O2 oxidation. The resulting poly(dihydrofuran) can be recycled to monomer via depolymerization with Grubbs catalyst or degraded to small molecules by hydrolysis under acidic conditions. This work opens exciting opportunities for a new class of ROMP monomers that lead to degradable polymers.

Olefin metathesis-crosslinked, bulky imidazolium-based anion exchange membranes with excellent base stability and mechanical properties

To improve the mechanical properties of anion exchange membranes (AEMs) with bulky imidazolium cations, a series of anion-conductive poly(2,6-dimethyl-phenylene oxide)s (PPO)s with crosslinkable terminal double bonds were synthesized by the Menshutkin reaction. Following crosslinking via olefin metathesis at room temperature catalyzed by a Grubb's second generation catalyst, tough, transparent, and flexible PPO-based AEMs were obtained. The crosslinked AEMs exhibited good mechanical properties (tensile strength at maximum load of 20.8–49.9 MPa and values of elongation at break of 1.5–3.0%) though their bulky imidazolium cation groups which could destroy the film-forming ability of polymer. And the obtained mechanical properties were considerably better than those of the non-crosslinked AEMs with a similar architecture, which broke into small pieces during the process of membrane fabrication using solvent casting. Furthermore, the crosslinked AEMs exhibited an extremely low water uptake (up to 13.9 wt% at 80 °C) and minimal swelling (<7% at 80 °C), attributed to the high-density crosslinking network. A high bromide conductivity (22.9 mS/cm at 80 °C) was achieved despite the low water uptake for the crosslinked AEM. Moreover, long-term alkaline stability testing in 1 M NaOH at 80 °C, no obvious degradation of the imidazolium ring was observed, with the conductivity of aged crosslinked membranes remaining at ~100% after 960 h. It was assumed that the bulky substituents at the C2, C4, and C5 positions of imidazolium cations and the crosslinked architecture prevented H2O and/or OH− from attacking the cationic center. Moreover, the AEM fuel cell performance and durability was further explored for the membrane electrode assembly (MEA) with crosslinked and uncrosslinked bulky imidazolium-based ionomers in catalyst layers. An optimistic cell performance (a peak power density of 173 mW/cm2 at 410 mA/cm2) and improved short-term durability at a constant current density of 200 mA/cm2 were obtained for the crosslinked ionomers, and its lifetime was ca. 3 times longer than that of benzyltrimethylammonium functionalized PPO ionomer.

First total synthesis of 5(S)-hydroxyrecifeiolide

The first total synthesis of recently isolated 5(S)-hydroxyrecifeiolide has been described in ten straight forward linear steps with 14% of overall yield. The key reaction involves Jacobsen’s hydrolytic kinetic resolution, Copper catalysed Grignard reaction, Steglich esterification and ring closing metathesis reaction using Grubb's 2nd generation catalyst making the synthesis very elegant and simple. The stereogenic center at C5 was generated via Jacobsen's HKR which was confirmed by the Mandelate ester strategy as well as HPLC purity.

Algorithmic Discovery of Tactical Combinations for Advanced Organic Syntheses

Summary Whereas most organic molecules can be synthesized from progressively simpler substrates, syntheses of complex organic targets often involve counterintuitive sequence of steps that first complexify the structure but, by doing so, open up possibilities for pronounced structural simplification in subsequent, downstream steps. Such complexifying/simplifying reaction sequences, called tactical combinations (TCs), can be quite powerful and elegant but also inherently hard to spot—indeed, only some 500 TCs have so far been cataloged, and even fewer are routinely used in synthetic practice. This paper describes computer-driven discovery of large numbers of viable TCs (over 46,000 combinations of reaction classes and ∼4.85 million combinations of reaction variants), the vast majority of which have no prior literature precedent. Examples—including a concise wet lab synthesis of a small natural product—are provided to illustrate how the use of these newly discovered TCs can streamline the design of syntheses leading to important drugs and/or natural products.

Synthesis of Stilbene and Chalcone Inhibitors of Influenza A Virus by SBA-15 Supported Hoveyda-Grubbs Metathesis

Stilbene and chalcone derivatives with biological activity against influenza A virus have been synthesized by self-, cross-, and ring-closing metathesis procedures. The reactions were performed under environmentally friendly conditions using the second generation Hoveyda-Grubbs catalyst Aquamet SiPr after immobilization on Santa Barbara Amorphous mesoporous silicate SBA-15. Irrespective from the experimental conditions, the heterogeneous catalyst showed activity and selectivity comparable than the homogeneous counterpart for at least six successive runs without appreciable leaching of the active species. An appreciable antiviral activity against influenza A virus for some of the novel derivatives were observed, mainly involving the early stage of the virus-replication life-cycle.

RCM vs Oxacycloisomerization through Divergent Reactivity of Dienyl‐ or Ynenylcycloalkanols using Grubbs Catalyst: an Access to Carbobicycles and Fused Bicyclic Dihydrofurans

AbstractStarting from simple cyclic 1,3‐ketoesters, a three‐steps sequence including allylic or propargylic allylation, 1,2‐addition reaction of functional Grignard reagent and alkylidene ruthenium‐catalyzed cyclization yields to carbobicycles and/or bicyclic dihydrofurans depending on the nature of the insaturation (diene or enyne). If the classical ene‐ene ring closing metathesis is observed with dienyl substituents, similar enynes led to enyne ring closing metathesis or oxacycloisomerization products depending on the chain length. In the case of ene‐yne systems with appropriate longer carbon chains, under the same conditions, metathesis reations give access to bicyclic dihydrofurans through oxacycloisomerization, demonstrating that it is possible to orient the activity of the Grubbs reagent.

Acid-Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water.

The ability to use unprotected carbohydrates in olefin metathesis reactions in aqueous media is demonstrated. By using water-soluble, amine-functionalized Hoveyda-Grubbs catalysts under mildly acidic aqueous conditions, the self-metathesis of unprotected alkene-functionalized α-d-manno- and α-d-galactopyranosides could be achieved through minimization of nonproductive chelation and isomerization. Cross-metathesis with allyl alcohol could also be achieved with reasonable selectivity. The presence of small quantities (2.5 vol %) of acetic acid increased the formation of the self-metathesis product while significantly reducing the alkene isomerization process. The catalytic activity was furthermore retained in the presence of large amounts (0.01 mm) of protein, underlining the potential of this carbon-carbon bond-forming reaction under biological conditions. These results demonstrate the potential of directly using unprotected carbohydrate structures in olefin metathesis reactions under mild conditions compatible with biological systems, and thereby enabling their use in, for example, drug discovery and protein derivatization.