Scholz, J,; Loekman, S.; Szesni, N.; Hieringer, W.; Görling, A.; Haumann, M.; Wasserscheid, P.  “Ethene-Induced Temporary Inhibition of Grubbs Metathesis Catalysts.”  Adv. Synth. Catal.  2011, 353, 2701-2707.

An interesting article emerged late last year in which the authors wanted to obtain some kinetic data employing immobilized Grubbs catalysts in continuous flow gas-phase reactions of unfunctionalized olefins. They immobilized a variety of Grubbs catalysts onto calcined silica using the SILP (supported ionic liquid phase) technique. This technique involves supporting the catalyst in a thin film of ionic liquid on a porous support. These types of materials had previously been reported and were shown to be effective catalysts for RCM in batch reactions with an ability to be recovered and recycled a few times.¹

When the SILP materials were employed under continuous flow conditions using fixed-bed reactors to study the self-metathesis of propene (products = ethylene and 2-butene with an equilibrium conversion of 34%) a very rapid decrease in propene conversion was observed, indicative of catalyst decomposition or deactivation. In an attempt to determine the effect that the ionic liquid had on this phenomena, a series of different SILP’s were prepared with different ionic liquid anions; however, no direct correlations between the anion’s coordination strength or the thermal/hydrolytic stability were observed. Upon further cogitation, an inverse correlation was observed between the stability of the SILP catalyst and the solubility of ethylene within the specific ionic liquid (i.e. the least stable SILP catalyst is composed of the ionic liquid that has the highest ethylene solubility).

In an attempt to validate the hypothesis that ethylene was responsible for the dramatic decrease in catalytic activity, a series of experiments were performed. First off, in a set of independent experiments, the catalyst bed was first subjected to a flow of ethylene gas for varying amounts of time before propene was introduced to the system. This set of experiments revealed that indeed, the catalyst beds that were subjected to larger amounts of ethylene had diminished initial activity upon the switch to propene. However, in a somewhat intriguing observation, it was seen that after the switch to propene, the catalyst actually regained some activity, reaching a maximum conversion shortly after the propene switch, before observing the same decrease in propene conversion described previously. This was suggestive that some sort of catalyst deactivation and subsequent re-activation process was in operation.

The authors performed some DFT calculations on possible reaction intermediates, and observed that the lowest energy species were ethylene-based metallacycles that would not be involved in the productive metathesis catalytic cycle (e.g., ruthenacycle F in the proposed catalytic cycle shown below). This effectively serves to remove “active” catalyst from the productive cycle, thus, diminishing the apparent overall catalytic activity.  In this case, ethylene is responsible for shifting the metallacycle equilibrium to an inactive or dormant state without irreversible catalyst deactivation (i.e., catalyst decomposition).

To test this second hypothesis, an experiment was devised where a metathesis reaction having a negligible contribution from ethylene was monitored using this fixed-catalyst-bed protocol. Flowing a C₄ gas mixture of 1-butene (6%) and 2-butenes (94%) diluted in an inert butanes atmosphere through the fixed-bed with a short residence time of 8 s resulted in the productive metathesis reaction generating products 1-propene and 2-pentene with an equilibrium conversion of 96%. In impressive nature, over the course of 20 h, there was no apparent catalyst deactivation for this process with the conversion remaining constant at 96%. At this stage, a 50:50 mixture of ethylene and 2-butene was then passed through the catalyst bed. As expected, the conversion of 2-butene decreased dramatically over time due to the catalyst deactivation (dormant state) in the presence of ethylene. When the substrate stream was switched back to the initial diluted 1-butene/2-butenes mixture, the equilibrium ratio of 96% conversion was quickly achieved, indicating catalyst re-activation. To push the limits, this feedstock switch was repeated two additional times, with equilibrium being reached quickly for each switch back to the diluted C₄ stream. Very impressively, the total time on-stream for this catalyst bed was greater than 500 h without any observed decrease in the catalyst efficiency for the conversion of the C₄ stream. However, the authors point out that an irreversible effect is observed, having a negative impact on the conversion of 2-butene, each time the stream is cycled back to the ethylene/2-butene mixture.

This is a very interesting phenomenon that was observed, and it will be crucial to determine the exact nature of this ethylene induced “deactivation” as ethylene plays a major role in a number of olefin metathesis processes as either a reactant or reaction by-product. Do similar processes occur in homogeneous catalysis? Is this isolated to heterogeneous SILP-based systems? What about other types of heterogeneous catalyst systems? These are important questions that will need to be addressed.

¹ (a) Hagiwara, H.; Okunaka, N.; Hoshi, T.; Suzuki, T.  “Immobilization of Grubbs Catalyst as Supported Ionic Liquid Catalyst (Ru-SILC).”  Synlett.  2008, 1813-1816.  (b) Hagiwara, H.; Nakamura, T.; Okunaka, N.; Hoshi, T.; Suzuki, T.  “Catalytic Performance of Ruthenium-Supported Ionic-Liquid Catalysts in Sustainable Synthesis of Macrocyclic Lactones.”  Helv. Chim. Acta  2010, 93, 175-182.

Kwon, Y., Lee, S., Oh, D.-C. and Kim, S. (2011), Simple Determination of Double-Bond Positions in Long-Chain Olefins by Cross-Metathesis. Angewandte Chemie International Edition, 50: 8275–8278. doi: 10.1002/anie.201102634

The accurate determination of the double-bond position in unsaturated long-chain compounds remains a challenging task. Current analytical techniques rely on analyzing fragment ions by mass spectrometry, but conventional methods of ionization such as EI and CI are not very reliable. More detailed and reliable information can be obtained after derivatization of the double bond. Transformations used include ozonolysis, epoxidation, dihydroxylation, alkylthiolation and methoxymercuration. With the products of these reactions, usually a second derivatization is necessary to make them suitable for GC- or LC-MS. In addition, these reactions are not very tolerant of the presence of other functional groups.

Cross Metathesis (CM) of long chain olefins with a simple cross partner offers a straightforward way to determine the double bond position. Instead of looking at the fragment ions of the parent molecule by GC-MS, the double bond is reacted with another olefin. The position of the double bond then can be simply deduced from the mass of the cross products. In addition, the CM reaction is very mild and can tolerate different functional groups in the molecule.

In one set of reactions, using methyl acrylate as the cross partner and the second generation Hoveyda-Grubbs catalyst was found to be optimal for LC-MS analysis. The starting materials for these reactions are easily available, can be handled on the bench, they don’t yield a mixture of double bond isomers and the α,β-conjugated double bond is perfect for detection with the common diode-array UV detectors. The procedure is pretty simple: just dissolve the target molecule in DCM/ethyl acrylate, add catalyst, stir for 2-3h, inject the mixture into a LC-MS and analyze the data. The example with elaidic acid (trans-9-Octadecenoic acid) clearly shows that the double bond is at the C-9 position by looking at the mass of the cross product.

Acids with two double bonds gave only the cross product with the first double bond (from the carboxylic terminus) with the second generation Hoveyda-Grubbs catalyst, but with the second generation Grubbs catalyst a second major peak was observed corresponding to the product of the second double bond.

The second set of reactions, using 2-methyl-2-butene as the cross partner and the second generation Grubbs catalyst, was used for GC-MS analysis. The procedure is similar to the one used for the LC-MS. In this case the catalyst has to be removed before injection into the GC-MS. Only one of the cross products, the 2-methyl-2-undecene is seen by GC-MS without derivatization, but it’s enough to determine the position of the double bond. The second product, the 9-decenoic acid, can be seen after conversion into the methyl ester.

This set of conditions wasn’t tested with molecules with more than one double bond; it’s interesting to see if the position of a second double bond can be determined. This method can be useful to check for double bond isomerization as well.

The method is very simple and can be applied to numerous double bond containing compounds, and can become a valuable tool in analytical chemistry.

Keitz, B. K.; Grubbs, R. H.  “Probing the Origin of Degenerate Metathesis Selectivity via Characterization and Dynamics of Ruthenacyclobutanes Containing Variable NHCs.”  J. Am. Chem. Soc., 2011, 133 (40), 16277-16284.

Back in September of 2010, ATM’s very own Andy Nickel wrote a post on a publication from the Grubbs group describing non-productive events during ring-closing metathesis reactions with Grubbs-type catalysts. The results showed that catalysts containing unsymmetrical alkyl-aryl NHCs lead to more non-productive or degenerate metathesis events. Perhaps in a challenge to the olefin-metathesis community, Andy stated:

“Nailing down why this is the case may not only help in the next round of catalyst design, but could also provide insight into the mechanism of catalyst-olefin coordination.”

It appears that B. K. Keitz and Prof. Grubbs accepted Andy’s challenge and commenced studies to elucidate the reason for this phenomenon employing new Piers-type phosphonium alkylidenes (Figure 1) as precursors to study ruthenacyclobutanes via low-temperature NMR spectroscopy.

Figure 1.  New Piers-type phosphonium alkylidenes employed to probe the origin of degenerate events during RCM reactions.

In a procedure adopted from the Piers’ laboratory², Ru-complex 1 was reacted with cyclopentene 4 and 1 equivalent of ethylene at -78 °C, which resulted in the formation of ruthenacyclobutane 5 in 29% yield. This was also accompanied by 21% of the unsubstituted ethylene-only ruthenacycle 6. (Scheme 1) Disappointingly, under the same conditions, when complexes 2 and 3 were employed, the ethylene-only ruthenacyclobutanes were the only ruthenacyles observed.

Low temperature NMR experiments were performed to study chemical exchange within ruthenacycle 5; however, under the conditions tested there was no evidence of exchange processes occurring. This is in stark contrast to the parent H₂IMes derived rutheacyclobutane which undergoes both intra- and intermolecular exchange processes.

Studies were then undertaken to determine the kinetics for the transformation of 5 to 6 via loss of cyclopentene 4 under an ethylene atmosphere (Scheme 2). These experiments were complicated by the fact that under all reaction conditions, an unknown ruthenacycle was generated that made the kinetic analysis rather difficult. However, through a clever design of experiments and some computer modeling, kinetic parameters were determined, and it was found that rate constant (k₁) for the conversion of 5 to 6 was 2 orders of magnitude smaller than observed with the parent H₂IMes ruthenacycle. From subsequent Eyring plot analysis, this corresponded to an approximate 2 kcal/mol higher energy barrier for this transformation compared again to the H₂IMes system. The authors caution of drawing too many conclusions from the data due to the specialized conditions employed for these studies; however, this increased energy barrier can help explain why catalysts comprising unsymmetrical alkyl-aryl NHC’s are generally less effective catalysts and why more degenerate events occur versus productive ring-closing when these mixed alkyl-aryl type catalysts are utilized.

Finally, in a personal discussion with B. K. Keitz concerning this research project, I asked him what his motivation was for performing this work:

“Our initial goal was to elucidate the entire productive RCM potential energy surface in a manner similar to Piers’ work, but using different catalysts. That was a little overambitious, but we did learn that the structure of the NHC has a profound effect on very fundamental metathesis reactions.”

Indeed, this is an important discovery and shows how what I would deem a very minor change in catalyst structure can have a large impact on the outcome of a metathesis reaction. With the ever-expanding use of olefin metathesis on an industrial scale, it’s clear that fundamental studies such as this will continue to be instrumental for the further development of the technology.

¹ Stewart, I. C.; Keitz, B. K.; Kuhn, K. M.; Thomas, R. M.; Grubbs, R. H.  “Nonproductive Events in Ring-Closing Metathesis Using Ruthenium Catalysts.”  J. Am. Chem. Soc., 2010, 8534-8535.

² (a) van der Eide, E. F.; Romero, P. E.; Piers, W. E.  “Generation and Spectroscopic Characterization of Ruthenacyclobutane and Ruthenium Olefin Carbene Intermediates Relevant to Ring Closing Metathesis Catalysis.”  J. Am. Chem. Soc., 2008, 130, 4485-4491.  (b) van der Eide, E. F.; Piers, W. E.  “Mechanistic insights into the ruthenium-catalysed diene ring-closing metathesis reaction.”  Nat. Chem., 2010, 2, 571-576.

Oehninger, L., Alborzinia, H., Ludewig, S., Baumann, K., Wölfl, S. and Ott, I. (2011), From Catalysts to Bioactive Organometallics: Do Grubbs Catalysts Trigger Biological Effects?. ChemMedChem. doi: 10.1002/cmdc.201100308

Organometallic compounds are primarily used in catalysis, however, some of them have been found to have important biological properties as well. In the early 60s’, the discovery that some platinum complexes had the ability to inhibit the division of living cells led to the development of several platinum-containing anti-cancer drugs such as cisplatin, carboplatin or oxaliplatin.

To date, platinum remains the major player in the development of new bioactive metal complexes, but ruthenium containing agents have also shown some promise. Two ruthenium[III] anticancer agents NAMI-A and KP1019 are currently in clinical trials. Half-sandwich ruthenium[II] complexes such as RM175 or RAPTA-C also exhibit interesting activities, which prompted researchers in Germany to investigate the possible biological relevance of other well-known ruthenium[II] complexes: the Grubbs-type catalysts G1, G2, HG1 and HG2.

All catalysts were found to inhibit tumor-relevant enzymes such as the thioredoxin reductase (TrxR) and the protease cathepsin B (catB). The inhibition of the enzymatic activity was observed with the order of activity G1<G2<HG1<HG2. For the second-generation Hoveyda-Grubbs complex HG2, the EC₅₀ values were in the low micromolar range, values comparable to those reported for RAPTA-type complexes.

The ability of the catalysts to inhibit the growth of cultured tumor cells (MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells) was also probed. Once again, the second-generation Hoveyda-Grubbs was the most potent, and displayed noticeable antiproliferative effects with IC₅₀ values of 9.9 µm (MCF-7) and 13.4 µm (HT-29). For reference, in the same assay, the IC₅₀ values for cisplatin are 2.0 µm (MCF-7) and 7.0 µm (HT-29).

Finally, G1, G2 and HG2 were also found to influence cell metabolism.

Even though Grubbs catalysts are not potent enough to be the next anti-cancer drugs, they undeniably displayed a certain biological activity, especially for the second generation. Further investigation on the toxicity and specificity of Grubbs-type catalysts would be very useful.

Miao, X.; Dixneuf, P.H.; Fischmeister, C.; Bruneau, C. “A green route to nitrogen-containing groups: the acrylonitrile cross-metathesis and applications to plant oil derivatives.” Green Chem., 2011, 13, 2258-2271.

A straightforward route to organonitriles, versatile intermediates in organic synthesis, would be cross metathesis (CM) with acrylonitrile. Unfortunately, acrylonitrile is definitely not the best substrate for metathesis reactions. Electron deficient olefins are generally difficult substrates for metathesis reactions, but α,β-unsaturated esters, aldehydes and ketones can be crossed with terminal olefins in good yields using second-gen Grubbs catalyst. Acrylonitrile is less reactive under these conditions, probably due to the strong ability of the nitrile group to coordinate to the metal and decompose the catalyst.

One of the first successful CM reactions with acrylonitrile was reported in 1995 using a Mo-catalyst, but required high catalyst loadings and the yields weren’t the best.

Most Grubbs catalysts failed miserably in the CM of acrylonitrile with different substrates. Second-gen Hoveyda catalyst performed better, but high catalyst loadings were required and the outcome of the reaction depended a lot on the cross partner. It’s noteworthy that, independent of the catalyst used, more of the Z-olefin was formed in contrast to all other electron deficient substrates which show a high degree of E-selectivity. Fast initiating catalysts such as bis(3-bromopyridine) and mono(2-methylpyridine) second-gen catalysts were comparable to the Hoveyda.

Crosses with acrylonitrile with different partners were studied in the Blechert group in 2001. Most reactions gave decent yields of the cross products with the second-gen Hoveyda, but the catalyst loadings were pretty high (5-8%). Even methacrylonitrile produced the trisubstituted olefin in good yields. The reaction is very selective; a mixture of acrylonitrile and methyl acrylate produced almost exclusively the nitrile cross product. Usually no dimerization of the acrylonitrile was observed and very little of the homocoupled cross partner was formed with excess of acrylonitrile.

Using additives such as CuCl or Ti(OPrⁱ)₄ improved significantly the yields of acrylonitrile cross products with the Grubbs second-gen catalyst. Increases of 20-30% were seen when 20mol% Ti(OPrⁱ)₄ was used as an additive. For the first time, even an internal olefin was crossed in the presence of CuCl in 57% yield. It turned out that the concentration of the reaction mixtures was crucial for the outcome of the cross reactions: decreasing the concentration from 0.5M to 0.07M more than doubled the yield with the Hoveyda second-gen catalyst. Microwave irradiation was also found to increase the yields of the reaction.

CM of unsaturated fatty acid derivatives from plant oils with acrylonitrile offers the possibility of producing high value added products from renewable resources but, due to the difficulties even with simple olefins, was not attempted until recently. High temperature, low concentration and excess of acrylonitrile were necessary to achieve high yields. Once again the second-gen Hoveyda catalyst performed best. Adding the catalyst using a syringe pump allowed for the catalyst loadings to be decreased to 0.025mol% for the CM of methyl undec-10-enoate with acrylonitrile. No self metathesis of the methyl-10-undecenoate was observed under the reaction conditions.

CM of an internal olefin with acrylonitrile using the syringe pump addition method gave 88% yield of the desired functional nitrile compound. Even though some of the ethenolysis product was formed under these conditions, the catalyst loading was remarkably low for a cross between an internal olefin and acrylonitrile (0.05mol%). Even the cross between fumaronitrile and the same internal olefin worked very smoothly with 5mol% catalyst, however only 50% conversion was reached with 1 mol% catalyst.

The Green Chemistry review shows how the development of new metathesis catalysts and careful optimization of the reaction conditions can give good results with even the toughest substrates. There is still room for improvement, but CM with acrylonitrile has turned into a valuable route to produce organonitrile compounds.

Elevance Renewable Sciences announced its intent to go public by filing an S-1 with the SEC last month. In the process, they hope to raise $100 million to fund continued R&D, capital expansion, and product development. Founded in 2007, Elevance developed from a partnership between Cargill and Materia to couple Cargill’s expertise in agricultural oils and Materia’s expertise in olefin metathesis. The company makes green alternatives to traditional petroleum products made by the olefin metathesis of natural oils and is planning construction of three integrated “biorefineries” with a projected ultimate capacity of 2.2 billion lbs/yr of green chemicals and fuels.

This ambitious application of olefin metathesis definitely deserved a post on All Things Metathesis, but as I looked around, I realized that Jim Lane of Biofuels Digest already did a great job of summarizing the company here. He boils down Elevance’s 200+ page S-1 filing into a short and enjoyable read.

Elevance’s success is a testament to the scalability of metathesis in cost competitive commercial applications, and if things work out as they hope, their IPO will mark a significant advance in the use of renewable feedstocks as petroleum alternatives.

Endo, K.; Grubbs, R. H.  “Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis.”  J. Am. Chem. Soc.,  2011, 133, 8525-8527.

Recently, I wrote a post describing a series of Ru-olefin metathesis catalysts developed in the Grubbs’ laboratory, containing one sterically demanding X-type ligand as a replacement for the standard chloride ligand of the classic Grubbs-type catalyst. These species displayed greater cis-selectivity in a standard cross-metathesis assay¹ compared to the traditional 2^nd generation catalysts; however, they still provided the trans isomer as the major product. This E/Z selectivity is a difficult problem in olefin metathesis, owing to the thermodynamic nature of the process and the preference for the formation of the favored trans isomer.

Now, Koji Endo and Bob Grubbs have described the first report of a Ru-based catalyst that favors the formation of cis olefins, employing a novel chelated NHC catalyst architecture in conjunction with a pivalate ligand. The catalyst synthesis involves treatment of a standard 2^nd generation Grubbs-Hoveyda type catalyst with silver pivalate, which leads to a subsequent intramolecular C-H activation of the ortho-CH₃ group of the symmetrical mesityl NHC ligand, or of the CH₂ group of the 1-adamantyl substituent in the unsymmetrical adamantyl/mesityl NHC ligand. This marks the first report of such C-H activated chelates providing metathesis active complexes. Generally, this type of NHC ligand derived C-H activation occurs from coordinatively unsaturated species during a metathesis reaction, leading to catalyst decomposition.

Employing the standard cross-metathesis assay previously described, the chelated-adamantyl catalyst provides the heterocoupled product in 87% Z-selectivity at 64% reaction conversion. Interestingly, allylbenzene also undergoes self-metathesis during the above cross-metathesis assay, providing the homocoupled product in >95% Z-selectivity. Also noteworthy is the fact that the best experimental conditions involve performing the reaction in a 1:1 mixture of THF:H₂O, thus, dry solvents are not a requirement. However, it is noted that strict exclusion of oxygen is required.

The above work has led to a follow-up communication from the Grubbs’ group  describing the use of the chelated-adamantyl catalyst for the cis-selective homodimerization of terminal olefins.² The catalyst was effective for a variety of terminal olefin substrates, supplying the corresponding homocoupled products with high levels of Z-selectivity. The catalyst was also shown to be tolerant to a wide array of reaction solvents and temperatures (25 °C – 70 °C). Notably, these results compare favorably to those previously reported from the research groups of Professors Schrock and Hoveyda.³

Finally, as we can see from the concluding remark from this communication:

“However, despite the recent success of ruthenium and Group VI systems, new catalysts, which undergo more turnovers and function under practical experimental conditions, are clearly needed to tackle more advanced olefin substrates and metathesis reactions.”

There are still significant challenges to address when dealing with this difficult problem, and personally, I look forward to seeing what new research is spurred in this area from the Grubbs’ lab and the various other skilled laboratories that have active research programs in the field of olefin metathesis. Novel catalyst developments will ultimately provide new opportunities and applications for this versatile technology.

¹ Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H. “A Standard System of Characterization for Olefin Metathesis Catalysts.” Organometallics, 2006, 25, 5740-5745.
² Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H.  “Z-Selective Homodimerization of Terminal Olefins with a Ruthenium Metathesis Catalyst.” J. Am. Chem. Soc., 2011, 133, 9686-9688.
³ (a) Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. M. “Highly Z-Selective Metathesis Homocoupling of Terminal Olefins.” J. Am. Chem. Soc., 2009, 131, 16630-16631.  (b) Marinescu, S. C.; Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. M.  “Room-Temperature Z-selective Homocoupling of ?-Olefins by Tungsten Catalysts.”  Organometallics, 2011, 30, 1780-1782.

Wang, Y.; Jimenez, M.; Hansen, A. S.; Raiber, E.-A.; Schreiber, S. L.; Young, D. W. J. Am. Chem. Soc., 2011, 133, 9196–9199.

Gallenkamp, D.; Fürstner, A. J. Am. Chem. Soc., 2011, 133, 9232–9235.

A few months back two papers focusing on selective macrocyclization appeared in JACS. In general, small rings (e.g. 5- and 6-membered) can be formed without complication, but as ring size increases, things can get dicey. Oligomerization can be problematic in larger rings since you’re paying more of an entropic toll to cyclize. In addition, unless there’s a bias for either the E or Z isomer, you generally end up with a mixture (this of course isn’t a problem with small rings). To make things even more complicated, many macrocyclic natural products contain more than one olefin, which increases the potentially formed products even more.

Damian Young and coworkers at the Broad Institute were studying macrocylization reactions for diversity oriented synthesis. Young’s group introduced a silicon atom on one of the terminal olefins in their macrocyclization precursors and observed high selectivity for macrocyclization and for the E-silyl macrocycle in particular. The resulting trisubstituted olefinic products are presumably too hindered to re-enter the catalytic cycle, trapping the kinetic product. Importantly, Young and coworkers found that the less hindered catalyst shown below was needed for the highest yields, and the –Si(OEt)₂Me group stood out as the best of several silyl groups screened.

Though silyl substitution isn’t necessarily desired in target compounds, vinyl silanes can serve as versatile intermediates. Young simply protodesilylated them to make the Z-alkene, but they can also potentially serve as handles for further functionalization by cross coupling reactions.

Fürstner and coworkers showcased additional benefits of the vinyl silicon substituent. In their recent paper, they used the silyl group as both a protecting and stereochemical directing group for conjugated dienes. The bulky silyl group renders its olefin unreactive and also directs the newly formed olefin to the less hindered geometry. In their new synthesis of lactimidomycin, the Fürstner group used a trisubstituted vinyl silane as part of a tetraene macrocyclization precursor. They then used the hindered Dorta catalyst shown below to react selectively with the terminal olefins to produce their target macrocycle in good yield. The silyl group was cleaved in high yield with TBAF to provide the E, Z-conjugated diene present in the natural product.

The 19^th International Symposium on Olefin Metathesis and Related Chemistry (ISOM XIX) took place this year from July 10-15^th in the beautiful city of Rennes, France. Recent breakthroughs in olefin metathesis were presented by both new players in the field along with some of the metathesis pioneers. All three 2005 Nobel laureates in Chemistry, Robert H. Grubbs, Richard Schrock and Yves Chauvin were in attendance and both Professors Grubbs and Schrock presented stimulating plenary lectures.

Highlights of the week’s presentations include new developments in Z-selective metathesis reactions using ruthenium, molybdenum and tungsten complexes and improved methods for macrocylizations.

A few of my favorite talks were those presented by:

• Siegfried Blechert on natural product synthesis using metathesis cascades and new catalysts for enantioselective metathesis.¹
• Michael R. Buchmeiser on titanium and hafnium catalysts for simultaneous ROMP/vinyl insertion polymerization.²
• Lionel Delaude on bimetallic ruthenium-arene complexes and their activity for ROMP and RCM.³
• Steven T. Diver on cross couplings and ring-expansions using ene-yne metathesis.⁴

The excellent science was celebrated by everyone with the delicious local food and wine of Britanny and our glasses were raised to toast the field of metathesis. With the conclusion of ISOM XIX, we can now continue our work to solve the remaining challenges in metathesis with plans to present at ISOM XX in 2013, which will take place in Nara, Japan. We look forward to seeing you there!

¹ Kannenberg, A.; Rost, D.; Eibauer, S.; Tiede, S.; Blechert, S. Angew. Chem. Int. Ed. 2011, 50, 3299-3302.
² Buchmeiser, M. R.; Camadanli, S.; Wang, D.; Zou, Y.; Decker, U.; Kühnel, C.; Reinhardt, I. Angew. Chem. Int. Ed. 2011, 50, 3566-3571.
³ Borguet, Y.; Sauvage, X.; Zaragoza, G.; Demonceau, A.; Delaude, L. Organometallics 2011, 30, 2730-2738.
⁴ Clark, J. R.; Diver, S. T. Org. Lett. 2011, 13, 2896-2899.

Fluorinated surfaces are ideal for a wide range of applications, as they offer low surface energy, superior corrosion resistance, and extremely low coefficients of friction. However, polymers with these desirable properties can be difficult to form, and even more difficult to form as even coatings that adhere to complex surfaces. Two recent reports highlight the use of surface-initiated ring-opening metathesis polymerization (SI-ROMP) for generation of partially-fluorinated films (non-fluorinated backbone with fluorinated alkyl pendant groups) bound to the substrate surface. Metathesis polymerization allows for rapid generation of these polymer films under mild reaction conditions.

The Jennings group of Vanderbilt University presented a series of partially-fluorinated polymer films generated by SI-ROMP of norbornenes bearing perfluorinated carbon chains (NBF_n).¹ Mercaptobutanol-treated gold substrates were combined with norbornene dicarbonyl chloride to create metathesis-active initiators. These initiators were activated by second generation Grubbs catalyst, and exposed to solutions of NBF_n monomer to give rapid growth of dense films (NBF_n). Film thickness increased linearly with monomer concentration (from 0.005M to 1.0 M NBF_n), suggesting the ability to produce films from 50nm to 1.5μm with a 15-minute metathesis polymerization reaction. These thick pNBF_n films offered increased electrical resistance, decreased capacitance, improved polymer stability, and low critical surface energies.

Feng Zhou and colleagues at the Lanzhou Institute of Chemical Physics reported the use of a catecholic initiator to anchor the SI-ROMP of pentadecafluorooctyl-5-norbornene-2-carboxylate (NCA-F₁₅) to a range of metals and metal oxides.² TiO₂ nanotubes and alumina nanowires were modified by the metathesis-active catechol, activated by first generation Grubbs catalyst, and exposed to 0.25M solutions of NCA-F₁₅ for two hours to generate polymer films of 10-15 nm. These partially-fluorinated films created super-repellant surfaces with water-droplet contact angles greater than 160°. Similar films were generated with copper, silver, iron, zinc, aluminum, and titanium planar substrates.

These reports demonstrate that metathesis chemistry holds great potential for future developments in surface modifications.

¹ “Surface-Initiated Polymerization of 5-(Perfluoro-n-alkyl)norbornenes from Gold Substrates,” Christopher J. Faulkner, Remington E. Fischer, G. Kane Jennings. Macromolecules 2010 43 (3), 1203-1209

² “Surface-Initiated Ring-Opening Metathesis Polymerization of Pentadecafluorooctyl-5-norbornene-2-carboxylate from Variable Substrates Modified with Sticky Biomimic Initiator,” Qian Ye, Xiaolong Wang, Shaobai Li, Feng Zhou. Macromolecules 2010 43 (13), 5554-5560