Despite the huge advances in the area of olefin metathesis, better catalysts are still sought to increase the efficiency of ring closing metathesis (RCM) reactions and make them more applicable in industry¹. Recently, several modified second-gen Grubbs-Hoveyda catalysts were prepared and tested for RCM by the Plenio group. The goal was to develop faster initiating catalysts but at the same time to keep the inherent stability of the parent complexes. The approach relied on modification of the Hoveyda ligand, but rather than introducing substituents in the phenyl ring, the donor ability of the hetero-atom was decreased significantly by the utilization of O-Ar² and N-Ar³ donor groups. The resulting catalysts featured the excellent stability of the Hoveyda-type complexes but underwent full precatalyst initiation within a short period of time resulting in very fast RCM reactions.

The new 2-phenoxy-substituted Hoveyda complexes (e.g., 1)² were tested for RCM reactions with various substrates at low catalyst loadings (100-15 ppm). The new catalysts were very efficient in the formation of N-heterocycles: 15-25 ppm 1 yielded >90% product in only 15 min!

The N-Ar Hoveyda complexes (e.g., 2a, b) ³ were very active and efficient for RCM reactions as well. In addition to simple di-substituted double bonds, they were also very efficient in reactions giving tri-substituted unsaturated nitrogen heterocycles with only 50 ppm catalyst loadings.

The new Hoveyda complexes described by Plenio are a good compromise between activity and stability and can perform RCM reactions very fast and at low catalyst loadings. These new developments in the area of more active and stable catalysts can make the industrial use of RCM more cost effective and attractive.

¹For other examples of RCM with low catalyst loadings, see: Bieniek, M.; Michrowska, A.; Usanov, D. L., and Grela, K. Chem. Eur. J. 2008, 14, 806. Kuhn, K. M.; Bourg, J.-B.; Chung, C. K.; Virgil, S. C., and Grubbs, R. H. J. Am. Chem. Soc. 2009, 131, 5313. Gatti, M.; Vieille-Petit, L.; Luan, X.; Mariz, R.; Drinkel, E.; Linden, A., and Dorta, R. J. Am. Chem. Soc. 2009, 131, 9498. Kuhn, K. M.; Champagne, T. M.; Hong, S. H.; Wei, W.-H.; Nickel, A.; Lee, C. W.; Virgil, S. C.; Grubbs, R. H., and Pederson, R. L. Org. Lett. 2010, 12, 984. Urbina-Blanco, C. A.; Leitgeb, A.; Slugovc, C.; Bantreil, X.; Clavier, H.; Slawin, A. M. Z., and Nolan, S. P. Chem. Eur. J. 2011, 17, 5045. Kadyrov, R. Chem. Eur. J. 2013, 19, 1002.
²Kos, P.; Savka, R., and Plenio, H. Adv. Synth. Catal. 2013, 355, 439.
³Peeck, L. H..; Savka, R. D., and Plenio, H. Chem. Eur. J. 2012, 18, 12845.

Wathier, M.; Lakin, B. A.; Bansal, P. N.; Stoddart, S. S.; Snyder, B. D.; Grinstaff, M. W. “A Large-Molecular-Weight Polyanion, Synthesized via Ring-Opening Metathesis Polymerization, as a Lubricant for Human Articular Cartilage” J. Am. Chem. Soc. 2013, 135, 4930–4933

Mammals use natural lubricants, known as synovial fluid to keep their joints moving smoothly. With age, arthritis and other ailments, these fluids are frequently not present in sufficient quantities. In these cases the synovial fluid, which contains a high molecular weight polysaccharide known as hyaluronic acid, can be replaced by naturally occurring fluids from other organisms or chemically crosslinked hyaluronic acid (Synvisc). These replacement fluids, however, are susceptible to enzymatic degradation leading to the need for repeated treatments. Grinstaff and coworkers recently published an article in the Journal of the American Chemical Society about using ring-opening metathesis polymerization (ROMP) to synthesize synthetic joint lubricants. By mimicking the physical properties of the fluid rather than the chemical structure, the new ROMP-based synthetic “synovial fluid” can perform the desired joint lubrication function with decreased risk of enzymatic attack. The mechanical properties of bio-polymers are notoriously complex but Grinstaff and workers seem to have done an excellent job of separating out the key attributes of coefficient of friction, storage and loss moduli and optimizing them based on molecular weight which is readily controlled using ROMP.

ROMP of the readily available oxanorbornene carboxylic acid methyl ester monomer followed by hydrolysis provides high molecular weight polymers with the key carboxylate moiety necessary for the lubricating qualities expected in the presence of saline. Achieving a high molecular weight polymer was critical for this application in order to increase the residence time in the joint. By adjusting the monomer to catalyst ratio in the ROMP, Grinstaff and coworkers were able to achieve lubricants with molecular weights ranging from 2.5 MDa to 3.7 MDa. The coefficient of friction was evaluated in ex vivo experiments and compared with bovine synovial fluid (BSF) and Synvisc. The 2.5 MDa ROMP polymer had an equivalent coefficient of friction to the BSF and a lower coefficient of friction than Synvisc. Rheology studies indicated that the polymers have excellent properties for dissipating energy on load bearing surfaces. The loss and storage moduli were somewhat different from natural synovial fluids but were closer to the target than Synvisc whose crosslinking leads to a significantly higher viscosity. Finally, the ROMP polymers were not cytotoxic and were not degraded by the enzyme hyaluronidase.

As someone who has spent time studying ROMP-based biopolymers (and as someone who likes to go jogging), I am always excited to see a paper that further demonstrates that many polynorbornenes and/or polyoxonorbornenes are not cytotoxic. The medical community is often cautious about new materials and as more examples appear in the literature with in vitro or even in vivo uses of ROMP polymers, their comfort level will increase and enable greater possibilities for the use of ROMP for medical devices and tissue engineering.

The 245th ACS National Meeting & Exhibition is right around the corner and will be held in New Orleans, Louisiana from April 7-11, 2013. I guess it’s somewhat fitting that I happen to be writing this post on Fat Tuesday…#MardiGras! The theme of the spring meeting, “Chemistry of Energy & Food,” is fitting for New Orleans. As usual, we here at All Things Metathesis will provide some highlights of the noteworthy abstracts describing olefin metathesis based research.

A quick search of the technical program for “metathesis” provided an impressive 102 hits. Of course, all of these are not strictly olefin metathesis examples, with some being alkane, alkyne, ene-yne, etc… to name a few.

To kick things off, let’s see what the olefin metathesis Nobel Laureates will be up to in New Orleans. It doesn’t look like Richard Schrock will be present in the Big Easy, but some collaborative work from his and Hoveyda’s lab will be presented by Erik Townsend describing Z- and chemoselective metathesis reactions of 1,3-dienes. Bob Grubbs will be very busy in NO, warming up with a polymer focused talk on Monday April 8th, followed by 3 talks on Tuesday, April 9th, all in various honorary symposia.

The Grubbs group will also be well represented with a total of 10 poster and oral presentations. It looks like Z-selectivity will be the hot topic, with presentations from Lauren Rosebrugh, Brendan Quigley, Vanessa Marx and Myles Herbert all dealing with various applications of Z-selective metathesis. Other topics will include rapidly initiating catalysts (Alexandra Sullivan), further CAAC-based ethenolysis work from the collaboration between Grubbs and Guy Bertrand, and some non-metathesis work describing some transition-metal-free C-O bond cleavage along with some anti-Markovnikov Pd-catalyzed oxidation work.

A couple poster sessions caught my eye that contain a number of olefin metathesis presentations. On Monday, April 8th at noon, undergraduate research will be presented in Hall D of the Morial Convention Center, followed by the Sci-Mix from 8-10 pm later that evening.

There are a number of abstracts describing olefin metathesis as a key step in some complex molecule syntheses and relevant pharmaceutical targets. Select examples are:

• Two different members from Chris Vanderwal’s lab at UC Irvine will describe examples of their rearrangement metathesis strategies.
• A report from Steve Martin and co-workers describing efforts towards the total synthesis of antitumor agent IB-00208.
• Studies towards the lipoxygenase inhibitor, Tetrapetalone A, will be described by Peter Carlsen from Alison Frontier’s group at the University of Rochester.
• The formation of bridged heterocycles, important building blocks in drug discovery, will be presented by a group from Pfizer.
• Efforts towards the development of a macrocyclic HCV inhibitor will be described by scientists from Abbott.

A few other abstracts piqued my interest which I have added to my itinerary:

• Hassan Bazzi describing collaborative work with David Bergbreiter using their polyisobutylene-supported Ru-catalysts.
• A group from the Institute of Bioengineering and Nanotechnology in Singapore will present a macrocyclization strategy using catalysts constrained within the pores of mesocellular siliceous foams.
• Joe Clark from Steve Diver’s group will discuss efforts to advance the utility of ene-yne metathesis.
• Will we hear about some breakthroughs with iron for olefin metathesis applications by Owen Summerscales and John Gordon from Los Alamos?
• Molecular gyroscopes? Tobias Fiedler from the Gladysz lab at Texas A&M will describe his use of olefin metathesis to synthesis these interesting systems.
• Catherine Cazin will speak about synergistic ligand effects in Ru-catalysts.

And for the polymer lovers out there, the following look interesting:

• Chester Simocko from Ken Wagener’s lab at Florida will talk about using ADMET to prepare precision boronic ester polymers.
• Some collaborative work describing the synthesis of novel monomers for controlling alternating ROMP polymerization from Kathlyn Parker and Nicole Sampson at SUNY Stony Brook will be presented.
• Greg Tew from UMass Amherst will discuss cyclic polymer brushes generated using REMP.

Also, noteworthy of mention, the ACS Award in Industrial Chemistry sponsored by The ACS Division of Business Development and Management and ACS Division of Industrial and Engineering Chemistry will be presented to Dr. Anne Gaffney who is currently the Director of R&D, Specialty Materials at INVISTA™. Previously, Anne spent 5 years at Lummus Technology as the V.P. of Technology Development where she was directly involved in the commercialization of the Olefin Conversion Technology, which converts ethylene and 2-butene into propene via metathesis.

Finally, Materia will be sending a team to New Orleans, led by our Director of Communications, Mr. Tom Buel, along with scientists, Dr. Adam Johns, Dr. Brian Conley and myself. Please stop by and visit us at the ACS Exposition (Booth #811). If you are feeling brave, take our Metathesis Challenge to receive a free Materia “Got Catalyst!” t-shirt. They’re a hot commodity, so stop by early in the show! See you in New Orleans!

Khalimon, A.Y; Leitao, E.M.; Piers, W. E. “Photogeneration of a Phosphonium Alkylidene Olefin Metathesis Catalyst” Organometallics 2012, 31, 5634-5637. DOI: 10.1021/om3005965

Chemists are always searching for a finely tunable, robust catalyst. Often this is accomplished by the use of some type of external activation that not only allows control over the activation of the catalyst, but provides a more stable catalyst as well. Typically, catalyst activation has been accomplished thermally, but photoactivation has been another popular way to solve this problem. In 2009, Grubbs and coworkers tackled catalyst activation by introducing a catalyst that underwent photoactivation via a photoacid generator (PAG).¹ Recently, Piers and coworkers combined their earlier work with Heppert’s catalyst (1)^{2, 3} with a photoactivated system via a PAG, [Ph₃S]⁺[OTf]^-, used by Grubbs and coworkers to produce a catalyst that can be readily activated with UV light at 254 nm (Scheme 1).

Scheme 1. Light activation of Heppert’s ruthenium carbide (1).

Similar to Piers and coworkers’ earlier studies, the acid generated by irradiation of [Ph₃S]⁺[OTf]^- readily initiated Heppert’s ruthenium carbide 1 via protonation.³ As expected, the coordinating ability of the anions has an effect on the efficiency of the reaction. The less coordinating anions provided a more active catalyst and the complex (2) obtained with the [Ph₃S]⁺[OTf]^- demonstrated the optimal level of activity. A series of substrates were examined to evaluate the efficiency of the photogenerated initiation as well as substrates scope by looking at a range of reaction types such as ring-opening metathesis polymerization (ROMP) and ring-closing metathesis (RCM). Gratifyingly, all displayed high amounts of conversion (>99%).

After examining the breadth of reactivity, Piers and coworkers wanted to understand the impact of having the photogenerating catalyst present during the metathesis reaction. To their delight, they found that the side products generated from the catalyst were not detrimental to the reaction. However, they did note that prolonged irradiation times caused a significant increase in the reaction temperature and subsequently noticeable decomposition of ruthenium complex 2. In order to avoid the thermal decomposition of 2, Piers and coworkers introduced an excess of isopropoxy-2-vinylbenzene in an effort to trap the more thermally stable Hoveyda-Grubbs catalyst 3 (Scheme 2). Unfortunately, UV light could only generate catalyst 3 in 50% yield with these conditions due the polymerization of the vinylbenzene.

Scheme 2. Formation of Hoveyda-Grubbs catalyst (3).

The quest for new methods to activate the metathesis catalyst will continue as new boundaries are pushed. The use of photoactivated catalysts is very exciting and hopefully will shine a light into new territory for chemists and scientists to venture.

¹Keitz, B.K.; Grubbs, R.H. J. Am. Chem. Soc., 2009, 131, 2038-2039.
²Carlson, R.G.; Gile, M.A.; Heppert, J.A.; Mason, M.H.; Powell, D.R.; Velde, D.V.; Vilain, J.M. J. Am. Chem. Soc., 2002, 124, 1580-1581.
³(a) Romero, P.E.; Piers, W.E.; McDonald, R. Angew. Chem. Int. Ed., 2004, 43, 6161-6165. (b) Dubberley, S.R.; Romero, P.E.; Piers, W.E.; McDonald, R.; Parvez, M. Inorg. Chim. Acta, 2006, 359, 2658-2664.

Kong, J.; Chen; C.; Balsells-Padros; J., Cao, Y.; Dunn, R. F.; Dolman, S. J.; Janey, J.; Li, H.; and Zakuto, M.J. “Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Reaction” J. Org. Chem. 2012, 77, 3820.

Several years ago the chemical development group at Boehringer Ingelheim¹ used a ring closing metathesis (RCM) step to produce hundreds of kilos of the HCV protease inhibitor BILN 2061 for clinical trials, showing that RCM is a great way to generate a macrocycle on large scale. Recently, the process research group at Merck has developed a practical scalable route to the HCV protease inhibitor Vaniprevir utilizing a RCM reaction to form the 20-membered macrocyclic core of the molecule. The simultaneous slow addition of catalyst and substrate allowed them to avoid the high dilution conditions necessary for macrocyclization and sustain the catalyst activity during the reaction. Addition of 10 mol% 2,6-dichloroquinone suppressed the isomerization of the allylic diene to a styrene double bond and the formation of a 19-membered ring as a side product. Under these conditions the methyl ester 3 was formed in 91% yield. Hydrogenation of the crude product followed by crystallization gave the saturated macrocycle in 89% overall yield and excellent purity. It’s noteworthy that the metal content (both Ru and Pd) was <10 ppm in the product after the hydrogenation.

Unfortunately the success of the RCM reaction with low catalyst loadings was highly dependent on the purity of the starting material, and the ester 1 was an oil with limited options for purification. But the easily accessible free acid 2 was a nice crystalline solid and could be isolated consistently in high purity. The RCM of the free acid 2 worked under the same conditions used for the ester 1 and gave the macrocyclic acid 4 in great yield and purity.

¹Farina, V., Shu; C.; Zeng; X.; Wei, X.; Han, Z.; Yee, N. K.; and Senanayake, C. H. “Second Generation Process for the HCV Protease Inhibitor BILN 2061: A Greener Approach to Ru-Catalyzed Ring-Closing Metathesis” Org. Process Res. Dev. 2009, 13, 250.

Ohlmann, D. M.; Tschauder, N.; Stockis, J.-P.; Gooßen, Dierker, M.; Gooßen, L. J. “Isomerizing Olefin Metathesis as a Strategy To Access Defined Distributions of Unsaturated Compounds from Fatty Acids” J. Am. Chem. Soc. 2012, 134, 13716-13729.

As petrochemical feedstocks are depleted, the chemical community is charged with discovering and developing new methods to access value added olefins from bio-renewable feedstocks. Natural oils and their derivatives, such as oleic acid and methyl oleate, are desirable substrates because of their ubiquity. It is well established that metathesis catalysts can transform long chain fatty acids and esters into new, useful compounds. Self and cross metathesis compounds are produced when metathesis is carried out in the presence of another olefin (typically a small hydrocarbon such as ethylene or butylene). These products subsequently can be distilled from one another. This process is an example of the “bio-refinery” concept in which renewable feedstocks are transformed into value added chemicals on scale. Ideally such processes can fulfill demand for commodity chemicals currently derived from petroleum, at least in part.

The number and identity of compounds synthesized in the process described above is limited by the position of the double bond in the fatty acid. This highlighted research paper out of Technische Universität Kaiserslautern in Germany addresses that limitation by utilizing the concept of isomerizing olefin metathesis to create well defined distributions of olefins from fatty acids, increasing the number of new compounds produced from an olefinic substrate. This development was made possible by tandem catalysis and necessitated finding isomerization and metathesis catalysts that “play nice” together – compatibility in this type of system is crucial and requires particular attention to liberated ancillary ligands on the catalysts and to available bimolecular decomposition events. A key was identifying the dimeric palladium complex [Pd(μ-Br)(^tBu₃P)]₂ as an isomerization precatalyst. When combined with active metathesis compounds such as 1-3 (Scheme 2) it maintains its activity for isomerization and does not attenuate metathesis activity.

After separately testing the activity of several potential catalysts for isomerization and metathesis, the best catalysts were combined into one pot to demonstrate isomerizing self-metathesis of methyl oleate and oleic acid (Scheme 1). Broad product distributions (from C₈-C₃₂) were obtained at 60 °C. Interestingly, at lower temperatures isomerization selectively slowed down and product distributions were sharp and centered on self-metathesis products, allowing for a “tuning” of product identity. This is in contrast to sequential isomerization/metathesis in which the isomerization catalyst is removed prior to metathesis – product distributions are set by extent of isomerization and are typically bimodal. The cooperative, one-pot catalyst described here could be a very useful concept in a commercial setting allowing flexibility in the diversity of the product stream.

Scheme 1. Isomerizing metathesis of oleates.

Scheme 2. Examples of active metathesis and isomerization catalysts used throughout the paper

In the same vein, several more similar studies were undertaken in this research including isomerizing metathesis of simple olefins, isomerizing self-metathesis of other fatty acids, isomerizing ethenolysis of fatty acids, and isomerizing cross-metathesis of fatty acids with dicarboxylic acids. Though the details of these studies will not be discussed herein, I encourage you to read this paper in full. Some other interesting features of the chemistry stood out:

• In the cross studies, varying the ratio of cross-partner to fatty acid substrate allowed for tuning of the mean chain length
• Several metathesis catalysts were active for ethenolysis of fatty acids in the presence of isomerization catalyst
• Electron deficient olefins proved difficult cross partners and required high catalyst loadings
• Mathematical modeling using statistics software R was used to predict equilibrium distributions of product fractions and should be a useful tool for future studies

To be practiced on scale, catalyst loadings will probably need to be lowered and their availability in thousands of kilogram quantities considered. Overall however, I found this chemistry interesting and extremely promising, primarily because of its versatility in selecting desired product distributions. I look forward to watching the technology mature as new classes of substrates are considered and more active/stable catalysts are developed.
 

Amakawa, K.; Wrabetz, S.; Kröhnert, J.; Tzolova-Müller, G. Schlögl, R.; Trunschke, A. “In Situ Generation of Active Sites in Olefin Metathesis” J. Am. Chem. Soc. 2012, 134, 11462-11473.

Heterogeneous, silica-supported tungsten catalysts are used to conduct the most efficient and largest practiced metathesis reactions in industry (The Phillips Triolefin Process). Despite their prominence, these catalysts are less understood mechanistically than the solution phase metathesis processes with well-defined catalyst systems. Trunschke and coworkers have recently published new insights into solving this problem that has existed about as long as metathesis itself.

Traditional, heterogeneous catalysts for metathesis vary from Mo, W to Re and can be supported on alumina, silica or combinations of the two. Trunschke and coworkers focused on the traditional Mo on mesoporous silica (MoO_x/SBA-15). Through characterization of the surfaces, they found that after oxidative pretreatment, the surface exhibited strong Lewis and Brønsted acidity and molybdenum was in the highest oxidation state possible. Raman spectroscopy of the catalyst surface indicated the presence of Mo(VI) and the distinct absence of molybdenum in lower oxidation states, while IR spectroscopy showed the presence of H-bonded groups that are distinct from those present in the mesoporous silica alone. Secondly, ammonia treatment of the MoO_x/SBA-15 surface showed NH₃ adsorption, whereas, the SBA-15 did not.

With a basic understanding of the varied chemical surface they were working on, the Trunschke group then began investigating the target reaction. Microcalorimetry demonstrated a modest exotherm upon adsorption of propene on the control SBA-15 and a larger exotherm on MoO_x/SBA-15. It was found that the surfaces without molybdenum show reversible binding of propene whereas the surfaces with molybdenum showed irreversible absorption. It is inferred from these experiments that the irreversible propene adsorption on the MoO_x/SBA-15 is correlated with the formation of active sites. When Trunschke ran the numbers, they found that a whopping 1.5% of the molybdenum atoms contain active sites!

Now it gets interesting. The IR of MoO_x/SBA-15 with propene adsorbed showed stretching frequencies similar to those of isopropoxide. The control experiment of treating MoO_x/SBA-15 directly with isopropanol showed an IR sprectrum that correlated directly. This supports the theory that the propene is hydrated with the Brønsted acid hydroxyls on the Mo(VI) surface to generate coordinated isoproxide. In addition, small bands correlating to carbonyls are observed, indicating the oxidation of IPA generating acetone and thus reducing Mo(VI) to Mo(IV). A lower intensity of the carbonyls implies, however, that most of the isopropanol is not actually being oxidized to acetone and the majority of the molybdenum remains in the VI oxidation state with IPA adsorbed.
 
Based on this evidence, Trunschke proposed the mechanism shown below in which a second equivalent of propene adds to the Mo(IV) sites that have been generated by the dissociation of acetone to form the active carbene that is responsible for olefin metathesis.

Carbonyl signals have been previously reported on related metathesis heterogeneous surfaces and have led to a proposed “pseudo-Wittig” mechanism for formation of the active, metathesizing carbene. However, this new evidence for the generation of Mo(IV) centers by isopropanol formation and oxidation to acetone is compelling and not consistent with the former “pseudo-Wittig” mechanism.

Although these heterogeneous metathesis reactions are among the most efficient metathesis reactions known, if only 1.5% of the molybdenum is involved in catalysis, it begs the question of how efficient could it really be? By inserting a pre-treatment involving propene adsorption-desorption, the authors found that the metathesis rate increased by about a factor of two but that the number of active sites did not increase.

It appears that increasing the number of active sites will be a challenge for future studies given the varied nature of the surface metal oxides. The studies by the Trunschke group present a significant stride forward towards improving these industrially relevant metathesis reactions.
 

Park, Hyeon; Choi, Tae-Lim. “Fast Tandem Ring-Opening/Ring-Closing Metathesis Polymerization from a Monomer Containing Cyclohexene and Terminal Alkyne” J. Am. Chem. Soc. 2012, 134 (17), 7270-7273. DOI: 10.1021/ja3017335

Sometimes two wrongs can make a right. Tae-Lim Choi and his group at Seoul National University have designed a monomer, which embodies this phrase by using  two unsuitable functional groups synergistically for a tandem relay Ring-Opening / Ring-Closing Metathesis (RO/RCM) polymerization. Monomer 1 contains two functional groups that are known to be problematic substrates for metathesis: the cyclohexene moiety polymerizes slowly, if at all, due to low ring strain¹ and the terminal alkyne is known to be resistant to polymerization (Scheme 1). However, the combination of these functional groups creates a monomer that readily undergoes polymerization.

Scheme 1. Tandem relay metathesis polymerization of monomer 1.

Initially the authors optimized for polymerization of monomer 1 with bis-pyridine catalyst 2, and discovered the reactivity to be similar to norbornene. With these optimized conditions, experiments were performed to understand the mechanism of the polymerization. Some initial control experiments showed the polymer produced was regio-regular with head-to-tail junctions. Having this information in hand, two distinct mechanistic pathways can be envisioned where either the terminal alkyne (Pathway A) or the cyclohexene (Pathway B) are involved in the initial step with the ruthenium catalyst. Due to the fast polymerization, pathway A, “alkyne first”, seems the most plausible to the authors owing to these reasons: the alkyne is less hindered than the cyclohexene, recent reports have shown the ruthenium carbene to react more readily with alkynes over alkenes², and finally reaction with the alkyne would generate a ruthenium diene, which is irreversible, whereas the carbene generated through pathway B, “cyclohexene first”, would be in equilibrium thereby slowing down the reaction. Furthermore, because the initial reaction with the alkyne proceeds quickly, the close proximity of the ruthenium carbene to the alkene can increase the rate of the cyclohexene opening, and secondly the irreversible formation of diene 1-A thermodynamically drives the polymerization forward.

Scheme 2. Potential mechanisms for tandem relay metathesis polymerization

The authors also investigated both block copolymerization and post functionalization of the new polymer. Since the polymerization of monomer 1 is a living polymerization, the addition of another monomer to create block polymers was explored and shown to be successful while retaining a narrow PDI (Scheme 3a). Furthermore, considering a diene is introduced into the polymer backbone, the polymer was shown to undergo post modification via a [4+2] cycloaddition (Scheme 3b). Interestingly, the cycloaddition with tetracyanoethylene only proceeded with trans-dienes.

Scheme 3.

1. Block copolymerization

2. Cycloaddition with the polymer

In conclusion, using unproductive functional groups for polymerization may seem counterintuitive, but a consideration for the spatial relationship of functional groups within a molecular framework can be a powerful approach. I am sure as chemists continue to take advantage of synergistic elements within the architecture of a monomer, the discovery of polymers with unique properties will expand in unforeseen directions.

¹Hejl, A.; Scherman, O.A.; Grubbs, R.H. Macromolecules, 2005, 38, 7214.
²Kim, K.H.; Ok, T.; Lee, K.; Lee, H.-S.; Chang, K.T.; Ihee, H.; Sohn, J.-H. J. Am. Chem. Soc. 2010, 132, 12027.

After the first generation of well-defined ruthenium metathesis catalysts were developed, most of the efforts in designing new catalysts concentrated on finding more and more reactive versions. However, more reactive catalysts are not suitable for ring-opening metathesis polymerization (ROMP) of very reactive monomers especially on a commercial scale. To solve this problem a number of latent catalysts were developed in recent years. Use of such catalysts in ROMP allows for the catalyst to be mixed with the monomer with little or no polymerization at room temperature. The latency of the catalyst allows for more time to handle the formulation or even store it for a prolonged period of time. Ideally, a latent catalyst should have no reactivity with the monomer at room temperature and then significant reactivity can be achieved when the catalyst is activated. The catalyst can be activated by chemical and physical methods including heat and light. In addition, the latent catalyst needs to have high thermal stability over time to enable a metathesis reaction to be carried out successfully at high temperatures.

The most widely applied strategy to design a latent catalyst is modifying the chelating ligand to slow down the ligand dissociation.¹ Catalyst 1, with a sulfur containing chelate, was found to be fully inert at room temperature to a series of reactive exo-norbornenes and cyclooctene. However, prolonged exposure to more reactive monomers such as dicyclopentadiene (DCPD) produced polymers even at room temperature. Recently, a new Catalyst 2 containing a second chelating sulfur atom was developed in the Lemcoff group.² This catalyst showed less than 1% conversion of DCPD after 2hrs at room temperature. Increased conversion can be achieved by raising the temperature. It’s noteworthy, that Catalyst 2 was completely inactive in ring closing metathesis reactions (RCM) even at elevated temperatures.

A different approach involving manipulation of the NHC ligand was used in the Grubbs group. Catalysts bearing a sterically hindered N-tert-butyl group on the NHC were prepared and tested.³

Catalysts 3a, b were tested for ROMP of functionalized norbornene monomers and COD (1,5-cyclooctadiene). The chloro-complex 3a was too reactive, but iodide exchange gave 3b which showed excellent latency and stability at room temperature. Quantitative conversion of functionalized exo-norbornene monomers was achieved at 85^oC in THF. The reactivity of the catalyst was solvent dependent; it was found that the latency is much higher in THF than in benzene. Similar to the sulfur chelates, this complex gave no RCM of diethyl allylmalonate even at 85^oC.

A lot of progress has been made in the development of new metathesis catalysts in recent years. Major efforts were focused on improving catalyst stability, functional group tolerance and improving TON and TOF. While controlled ROMP of highly active monomers still remains a challenge, the recent progress towards latent thermally stable catalysts is very encouraging.

¹ Recent Review: Y. Vidavsky, A. Anaby, and N. G. Lemcoff, Dalton Trans. 2012, 41, 32.
² Y. Ginzburg, A. Anaby, Y. Vidavsky, C. E. Diesendruck, A. Ben-Asuly, I. Goldberg, and N. G. Lemcoff, Organometallics 2011, 30, 3430.
³ R. M. Thomas, A. Fedorov, B. K. Keitz, and R. H. Grubbs, Organometallics 2011, 30, 6713.

The 244th ACS National Meeting & Exhibition is fast approaching and will be held in Philadelphia from August 19-23, 2012. The overall theme of the fall meeting is “Materials for Health & Medicine.” Sticking with tradition, we here at All Things Metathesis will give a brief overview of some of the noteworthy olefin metathesis related material that will be presented in Philly.

First and foremost, Materia and All Things Metathesis’ very own, Rosemary Conrad Kiser will be presenting in the N-Heterocyclic Carbenes in Catalysis symposium during the afternoon session on August 20th. This is a particularly olefin metathesis heavy session with 9 of the 10 scheduled talks dealing with the topic in some fashion. The session breakdown is as follows:

1. Siegfried Blechert will describe chiral Ru-catalysts containing unsymmetrical NHC ligands.
2. Catherine Cazin will present her groups research using mixed Ru-NHC/phosphite complexes.
3. Lionel Delaude will discuss some new Ru-benzimidazolylidene derivatives.
4. Karol Grela is scheduled to give an overview of his groups’ research in the field.
5. Gabriel Lemcoff will talk about some new methodologies using dimeric Ru-complexes and switchable catalysts.
6. Herbert Plenio will provide insight into the ethenolysis of rubber.
7. Renat Kadyrov will detail work done with low catalyst loading RCM studies.
8. Rosemary Conrad Kiser will discuss the versatility of the NHC ligand in catalyst design.
9. Michael Limbach will describe some continuous flow applications using heterogenized Ru-complexes.
10. Wiley J. Youngs will close out the session by giving everyone a break from olefin metathesis and present research on the antitumor activity of silver carbene complexes and imidazolium cations.

For all of you metathesis junkies, the above session is being held at the Pennsylvania Convention Center in room 125 on Monday August 20th from 1:30-5:05pm. I’ll see you there…

Secondly, it wouldn’t be much of an overview if we didn’t mention the exploits of Nobel Laureates Bob Grubbs and Richard Schrock. Professor Grubbs will give two polymer focused presentations in symposia honoring current postdoc Garret Miyake (AkzoNobel Award for Outstanding Graduate Research in Polymer Chemistry) and former student Chris Bielawski (Journal of Polymer Science Award) on Sunday and Monday respectively. Professor Schrock will also give a polymer focused lecture, in the ACS Catalysis Lectureship for the Advancement of Catalytic Science Award Symposium on Monday afternoon.

Some other olefin metathesis related presentations that look interesting are as follows:

• Susannah Scott will present work on studies aimed at understanding and improving supported perrhenate catalysts.
• Ken Wagener will talk about some solid state acyclic diene metathesis polymerizations, while his student, Michael Schulz, will describe some metathesis based depolymerization processes.
• Wing-Sy DeRieux, a student of Yann Schrodi, a former Materia employee and current professor at California State University, Northridge, will describe some efforts towards iron alkylidenes.

Finally, if you still haven’t gotten your fill of olefin metathesis and want to talk in more detail, please come visit us at the ACS Exposition (Booth #1719). If you stop by early enough during the show, we’ll have you take the Metathesis Challenge so that you can receive a Materia “Got Catalyst!” t-shirt… Sounds like a pretty good deal to me! Hope to see you in Philly!