催化中国, 中国催化分享 http://blog.sciencenet.cn/u/catachina 化学家(www.chemj.cn)

博文

Nature 8 November 2007 (pp135-318)金属有机催化综述

已有 5519 次阅读 2007-11-8 17:51 |个人分类:催化资源收藏



金属有机化学(Organometallic chemistry)
The remarkable metal-catalysed olefin metathesis reaction


催化性烯烃置换是一个功能强大的化学转化过程,可被用来将相对简单的含双键的化合物转化成更复杂的化学结构。为此,它引人注目地丰富了化学合成领域的内容,因为它可被用来制备天然产物、药类化合物和聚合物。在这篇Review文章中,Amir Hoveyda 和Adil Zhugralin对使得这一获得诺贝尔奖的反应得以进行的催化剂进行了讨论,介绍了置换过程何以可被用来合成复杂的天然产物,指出了仍然需要化学界去研究、以充分实现这一催化过程潜力的几个关键问题。

(Review Article p. 243)


Amir H. Hoveyda

个人主页:http://www2.bc.edu/~hoveyda/res.html

http://chemserv.bc.edu/hoveyda/

Amir H. Hoveyda is the Joseph T. and Patricia Vanderslice Millennium Professor of Chemistry at Boston College. He received his undergraduate education at Columbia University where he received a B. A. degree in 1981. He was a graduate student at Yale University with Professor Stuart L. Schreiber. After receiving his Ph.D. in 1986, he joined Professor David Evans at Harvard as an American Cancer Society postdoctoral fellow. In June 1990, Hoveyda joined the faculty at Boston College, where he was promoted to rank of Professor in 1994; in 1998, he was appointed to his present position. Hoveyda's research interests are in the development of new stereoselective reactions, organometallic chemistry, asymmetric catalysis, synthesis of complex natural products and combinatorial chemistry.


pdf全文连接

The remarkable metal-catalysed olefin metathesis reaction

 


 

Review

Nature 450, 243-251 (8 November 2007) | doidoidoi:10.1038/nature06351

The remarkable metal-catalysed olefin metathesis reaction

Amir H. Hoveyda1 & Adil R. Zhugralin1

Top

Catalytic olefin metathesis—through which pairs of C = C bonds are reorganized—transforms simple molecules to those that are complex and precious. This class of reactions has noticeably enriched chemical synthesis, which is the art of preparing scarce molecules with highly desirable properties (for example, medicinal agents or polymeric materials). Research in the past two decades has yielded structurally well-defined catalysts for olefin metathesis that are used to synthesize an array of molecules with unprecedented efficiency. Nonetheless, the full potential of olefin metathesis will be realized only when additional catalysts are discovered that are truly practical and afford exceptional selectivity for a significantly broader range of reactions.

To appreciate the importance of catalytic olefin metathesis, we must consider the power of chemical synthesis. The ability to prepare molecules is crucial to advances in medicine, biology and materials science1. Chemical synthesis challenges and expands our understanding of the fundamental principles of reactivity and selectivity, and gives us the opportunity to examine special molecules that were previously non-existent or available in such small quantities that a study was not feasible—for example, anticancer epothilones2, 3 and anti-hepatitis C agent 43 (see below). A recent remark by the director of the National Institutes of Health is apropos: "One interesting result of the NIH Roadmap development process came when we surveyed scientists to find out what the stumbling blocks for biological sciences were. The number one stumbling block turned out to be synthetic organic chemistry"4.

For synthetic chemistry to provide its full impact, certain advances must first be realized. One crucial area is catalyst discovery. Catalytic processes represent a degree of efficiency superior to those that require one or more equivalents of a reagent (ideally, one mole per cent catalyst or less should be used). Of particular significance is the identification of effective catalysts that are readily available, easy to handle, reliable, and promote transformations at high selectivity with a broad range of substrates with minimal waste generation. Catalytic olefin metathesis5, 6, 7, 8, 9, 10 is a ground-breaking advance that has significantly enhanced the power of chemical synthesis, and is likely to continue to do so.

Top

Olefin metathesis and its importance

Olefin metathesis ('metathesis' from the Greek meaning 'change of position, transposition') reorganizes the carbon atoms of two C = C bonds (olefins or alkenes), generating two new ones; it promotes unique skeletal rearrangements, and is significant for several reasons. First, some olefins are easy to prepare and others require more effort to access. Terminal and some disubstituted alkenes are prepared with relative ease; tri- or tetrasubstituted olefins, on the other hand, present a challenge owing to higher levels of steric hindrance and complications associated with controlling cis and trans (or E and Z) selectivity. Olefin metathesis allows facile access from the easily prepared olefins to those that are cumbersome to access. Efficient and stereoselective synthesis of the more substituted olefins is an important and largely unsolved problem in synthesis. Second, olefin metathesis reactions either do not generate a by-product or only produce one, such as ethylene, which can be removed by evaporation11. Third, chemists routinely use olefins to interconvert molecules. Olefins are useful largely because they present the better of two worlds: stability and reactivity. Olefins are stable—they are typically stored indefinitely without decomposition. And yet, olefins contain a pi-bond that is sufficiently reactive to be used in a wide range of transformations.

The repertoire of olefin metathesis catalysts

Olefin metathesis may be classified into three categories: cross, ring-closing and ring-opening metathesis (Fig. 1)12. Cross metathesis is the most pedagogically relevant version13. As shown in Fig. 1, with an appropriate catalyst, C1 = C2 and C3 = C4 can be transposed into C1 = C3 and C2 = C4. It is perhaps difficult to see, at first glance, why one set of olefins would be favoured; this is a key issue, as all olefin metathesis reactions are in principle reversible. The possibility that products might be re-converted to the starting materials dictates that chemists must design reactions that avoid back-tracking.

Figure 1: Different types of olefin metathesis.
Figure 1 : Different types of olefin metathesis. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

Cross metathesis, ring-closing metathesis and ring-opening metathesis: each represents a different type of reaction and furnishes a different kind of product.

High resolution image and legend (50K)

Another type, thus far the most widely used, is ring-closing metathesis (Fig. 1)14. Here, two terminal alkenes react with the catalyst to generate a cyclic olefin, releasing a smaller olefin (C2 = C4 in Fig. 1). Ring-closing metathesis reactions can proceed to completion partly because volatile by-products are removed, trumping a reverse process.

Finally, there is ring-opening metathesis15 (Fig. 1), through which a cyclic olefin reacts with a linear (acyclic) olefin, generating an acyclic diene. The driving force is the release of strain16 in ring structures; this also ensures minimal reaction back to the cyclic compound. Reactions that involve cross metathesis are mechanistically more complex, and controlling such transformations can be difficult (versus ring-closing). To promote cross metathesis, the catalyst must fuse together two different cross partners; otherwise, homodimerization predominates. Such complications do not occur in ring-closing metathesis where an intramolecular process is often preferred over an intermolecular one (unless strained and entropically disfavoured rings are sought17).

Catalysts that make it possible

Some of the olefin metathesis catalysts that are widely used and have served as the basis for a range of other systems are shown in Fig. 2. Centre-stage is a molybdenum (Mo; ref. 18) or a ruthenium (Ru; ref. 19) atom. The Mo = C or Ru = C double bonds (a Mo alkylidene or a Ru carbene) serve as points of contact between the catalyst and olefins. As we will see, the metal centres are crucial to the properties of these catalysts. Although complexes of other metals (such as tungsten18, 20, 21, rhenium22 and osmium23) promote olefin metathesis, these exhibit lower stability and/or reactivity, and have not been as extensively investigated. Development of such catalysts, however, is a compelling future objective, because—similar to Mo and Ru systems—additional metal complexes are likely to provide unique or complementary reactivity and/or selectivity profiles.

Figure 2: Representative olefin metathesis catalysts.
Figure 2 : Representative olefin metathesis catalysts. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

Catalysts 13 (top) are among the most commonly used achiral catalysts. Catalysts 46 (bottom) are chiral, and can react at different rates with two enantiomers of a substrate (kinetic resolution) or can convert an achiral molecule to a chiral one with preference for one of the two enantiomers (asymmetric synthesis). Mo-based catalysts 1 and 4 are air sensitive but generally more active than air-stable Ru-based catalysts 2, 3 and 5, 6, respectively.

High resolution image and legend (128K)

Mo catalyst 124, prepared and handled under inert atmosphere, is generally more active than Ru catalysts 225, 26, 27, 28 and 329 (Fig. 2), which are stable to air and moisture. The activity of Mo and Ru catalysts are, to a large degree, complementary18. Ru catalysts may be used with substrates that carry an alcohol, a carboxylic acid, or an aldehyde, but can be rendered inactive in the presence of structurally exposed amines30 and phosphines31; the reverse holds for Mo catalysts18. Metal complexes 13, as well as a number of Ru-based derivatives32, 33, 34, are commercially available.

Mo and Ru catalysts 4635, 36, 37 (Fig. 2) are chiral. Handedness, or chirality, is an attribute of many molecules of life; polypeptides, nucleic acids, carbohydrates, and numerous naturally occurring molecules that exhibit biological activity exist as a single enantiomer and consist of enantiomerically pure smaller units. A critical objective of modern chemistry is the development of catalysts38 that promote the formation of chiral molecules of high enantiomeric purity (ideally >98% purity) from readily available and inexpensive achiral ones39. Catalysts 46 initiate reactions that favour formation of one enantiomer. Thus far, Mo-based chiral catalysts, one of which is commercially available35, promote ring-closing metathesis with higher enantioselectivities for a wider range of substrates18, 36, 40; both classes are effective in enantioselective ring-opening/cross metathesis, affording carbo-37, 41 and heterocyclic products42, 43 (see below). The development of chiral olefin metathesis catalysts is less advanced than that of the achiral variants, and many important discoveries remain to be made. For instance, there are no effective chiral catalysts for enantioselective cross metathesis41.

Top

Catalytic ring-closing metathesis

A general pathway44 illustrating how such transformations proceed is shown in Fig. 3A. All olefin metathesis reactions involve association of the metal with an olefin substrate45, 46, 47. It is in this crucial interaction that one significant difference between Mo- and Ru-based catalysts presents itself. A high-oxidation-state Mo centre (+6) is a Lewis acid that chelates with a Lewis basic olefin; in contrast, in Ru catalysts, it is the alkene substrate that serves primarily as a pi Lewis acid48, 49.

Figure 3: The general mechanism for ring-closing olefin metathesis.
Figure 3 : The general mechanism for ring-closing olefin metathesis. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

This mechanism involves the intermediacy of metallacyclobutanes (A); also shown are two examples (B and C) that illustrate the power of catalytic ring-closing metathesis in the total synthesis of biologically active natural products (M = Mo or Ru). In both cases, the reversible nature of cross metathesis is critical to efficient synthesis of the desired macrocycles.

High resolution image and legend (153K)

Overall, the catalytic cycle (Fig. 3A) consists of an initiation phase (generation of the active complex) and a propagation phase (the active complex promotes additional cycles). Catalysis commences by a cross metathesis between an active carbene or alkylidene (M = C) and one of the two olefins of the substrate (i) to generate a metallacyclobutane (ii)50, 51. The metallacyclobutane might revert to i and M = C (pathway a) or the other two bonds of the ring might be ruptured, furnishing iii, where the metal (M) is within the substrate (pathway b). Formation of another metallacyclobutane (iv) and its disintegration furnishes cyclic product v and M = C3 (vi), which is the metal-bearing agent serving as the catalyst. What typically drives reactions is that the cyclic product (v) does not easily react with the active catalyst (M = C3) to cause ring-opening metathesis.

The identity of the intermediates in the catalytic cycle is well understood52; it is, however, often unclear whether it is catalyst–substrate association (i and vii first chelate with the metal centre of M = C before conversion to ii or viii), formation of the metallacyclobutane50, 53 or its cleavage that is the irreversible, product- or rate-determining step (Fig. 3A). It is a daunting task to predict a 'most effective catalyst' or to design—in the true definition of the word—one: what differentiates a selective process from one that is non-selective is a mere 2–2.5 kcal mol-1 difference in activation barriers (for example, rotation around the C–C bond of ethane requires only approx3 kcal mol-1), and seemingly insignificant alterations in the substrate structure or conditions can change the energetics of the catalytic cycle (which step is rate-determining)54. These considerations indicate that seeking a truly 'general catalyst' is likely to be futile —different classes of substrates may require a different 'optimal' catalyst. Chemists address such challenges through invention of a class of catalysts (as opposed to one compound) that are easily modified to achieve maximum reactivity and/or selectivity. The more readily modifiable a catalyst class, the larger the number of available catalysts, and the better the odds of obtaining more desirable results18.

There is little doubt that ring-closing metathesis has elevated the art and science of chemical synthesis55, 56. Two ring-closing metathesis reactions that have been carried out for the synthesis of the large rings of two natural products are shown in Fig. 3B. The linear chain of 7, with Lewis-basic and potentially catalyst-deactivating oxygen- and nitrogen-containing groups, is converted to the 14-membered ring lactam 8 by catalyst 157. In two additional steps, the product of ring-closing metathesis (8) is transformed to antifungal and anti-influenza agent fluvirucin B158. The volatile ethylene (H2C = CH2) is the by-product.

It is easy to appreciate the power of catalysis when one considers the alternative pathways—exits on a reaction highway either avoided or traversed reversibly. The challenge in any ring-closing is that a cross metathesis, such as generation of 9 (Fig. 1), represents a competitive route; the catalyst must be sufficiently active to reverse this 'wrong turn'. The two C = C bonds in 7 are not identical: one is the more accessible and reactive monosubstituted alkene. Formation of 9 is therefore of particular concern, since it arises from coupling of two molecules of 7 by a reaction of the less hindered olefins. How is it, then, that 8 can be prepared in 92% yield? The key lies in the reversibility of olefin metathesis. Substantial amounts of 9 are indeed formed, but catalyst 1 reverts 9 to 7. Macrocyclic 8, on the other hand, does not undergo further reaction (ring-opening); the central olefin of 9 is less hindered than the olefin in 8 (trisubstituted). The success of the seemingly straightforward closure of 7 to afford 8 involves several nuances. Efficient synthesis of the large ring depends on striking a balance among cross metathesis, a process that delivers the undesired coupling of two substrate molecules, ring-closing metathesis, a reaction that affords the desired product, and a ring-opening metathesis pathway that would dismantle the desired cyclic compound.

Another revealing example is the 'stitching' of two molecules of 10 to access 22-membered ring 12 en route to the cytotoxic agent cylindrocyclophane F (Fig. 3C)59. The homodimerization of 10 must transpire in the desired fashion, as the two olefins within each molecule of 10 are different. The coupling can occur in two ways: head-to-head or head-to-tail, and the head-to-tail is needed for the subsequent ring-closing metathesis that affords 12. The successful synthesis of 12 is not due to preferable formation of 11 over the alternative head-to-head product—it is because ring-closing metathesis of 11 is more favoured. Detailed investigations reveal that the head-to-head product is generated but is converted back to 10, which undergoes coupling to generate 11. The reversible nature of olefin metathesis proves crucial again.

In the case of 8, the olefin, generated through olefin metathesis, is erased by palladium-catalysed hydrogenation to establish the distal methyl-bearing stereogenic centre. To untrained eyes, fluvirucin B1 or cylindrocyclophane F are structures that do not contain an olefin within their macrocycle, and the idea of using olefin metathesis to access these molecules may not be evoked. When a synthetic chemist contemplates a target from the perspective of olefin metathesis, she must choose, among various possibilities, where to place an olefin in the precursor substrate, all signs of which may subsequently be erased. In designing a route, she commits to a strategy that predicates the identity of the bonds that realize their union. The chemist makes a move, one that affects the others that will follow1, 60.

The total synthesis presented in Fig. 4 is based on the insight that the architecture of longithorone A can be born through coupling of two (nearly identical) smaller building blocks 16 and 1961. Cyclizations of 13 and 17, providing the 15-membered rings of 15 and 18 (Fig. 4) are catalysed by Ru complex 1462, an earlier version of 2 (Fig. 1). These ring-closing reactions involve an alkyne in processes referred to as enyne metathesis63, 64, 65. Products 15 and 18 are transformed to 16 and 19 such that these unsaturated macrocycles can be directed to participate in two separate Diels-Alder additions, courtesy of enyne metathesis products. The protagonists in the first act are identified in red: the 1,3-diene of 19 (red) reacts with the olefin of 16 (red) to join the two pieces while generating a cyclohexene (red). This is followed by another cycloaddition between the 1,3-diene (blue) and an olefin (blue) that resides within 16.

Figure 4: A concise synthesis of longithorone A.
Figure 4 : A concise synthesis of longithorone A. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

This synthesis involves coupling of segments 16 and 19, both of which were prepared by ring-closing ene-yne metathesis reactions of 13 and 17, respectively. TBS (t-butyldimethylsilyl) is a common protecting group that masks alcohols.

High resolution image and legend (168K)

Top

Catalytic ring-opening and cross metathesis reactions

A general scheme illustrating the mechanism of ring-opening metathesis is depicted in Fig. 5. A cyclic olefin (ix) joins with a catalyst (M = C) to generate a metallacyclobutane (x), which may collapse to furnish a metal-containing intermediate xi. Acyclic xi can react with another acyclic olefin (C3 = C4 versus cyclic olefin x) to yield another metallacyclobutane (xii). Rupture of xii furnishes the final product (xiii) and affords the active catalyst (xiv), which propagates additional cycles. The second olefin metathesis sequence, involving conversion of xi to xiii, constitutes a cross metathesis, and hence the concatenation of events that converts ix to xiii is referred to as ring-opening/cross metathesis. If the cyclic olefin proves more reactive than the cross partner, or if a cross partner (for example, C3 = C4) is absent, xi can react with another molecule of ix. The resulting M = C transforms another ix and soon the active species romps through the substrate molecules, generating polymeric products. Such a process is referred to, appropriately, as ROMP (ring-opening metathesis polymerization). Alternatively, if the cross partner is more reactive (versus cyclic olefin), the major product arises from homo-coupling (cross metathesis). To achieve high yields of ring-opening/cross metathesis, the catalyst must react with the two substrates in the proper sequence with high precision. Such considerations pose demanding challenges in catalyst development. One recent approach involves catalysts that bear a stereogenic metal centre (for example, 6 in Fig. 2 and 49 below), leading to the intermediacy of two diastereomeric metal-carbene intermediates (M = C), each reacting preferably with the cyclic olefin or the acyclic cross partner42, 66.

Figure 5: General mechanism for catalytic ring-opening/cross metathesis.
Figure 5 : General mechanism for catalytic ring-opening/cross metathesis. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

Ring-opening metathesis is initiated by the rupture of a cyclic C–C double bond (olefin) by a catalyst (M = C). This affords a new alkylidene (xi), which undergoes cross metathesis with another olefin to furnish the final product (xiii).

High resolution image and legend (53K)

Small cyclic alkenes are strained16—they contain a substantial amount of energy that can be released on rupture (up to approx55 kcal mol-1; approx2 kcal mol-1 difference between two pathways means approx97% selectivity). Strain energies have been exploited to promote ring-opening/cross metathesis reactions15, 42. Two examples are presented in Fig. 6. In a total synthesis of cytotoxic agent bistramide A67, cyclopropene 20 participates in a catalytic ring-opening/cross metathesis with acyclic olefin 21 to yield 22. In a subsequent cross transformation, the more accessible alkene of 22 (blue) is set up to react with another acyclic olefin (23) to furnish 24 (and gaseous ethylene as by-product). Two olefin metathesis reactions are therefore used to stitch three molecules—20, 21 and 23—together, and, in short order, a complex molecule that constitutes a significant portion of bistramide A is fabricated.

Figure 6: Catalytic ring-opening/cross metathesis provides uniquely efficient pathways for synthesis of biologically active natural products.
Figure 6 : Catalytic ring-opening/cross metathesis provides uniquely efficient pathways for synthesis of biologically active natural products. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

In the total synthesis of bistramide A, a Ru-catalysed ring-opening cross metathesis is followed by another cross metathesis to furnish 24. In the total synthesis of baconipyrone C, a chiral Ru catalyst converts achiral 25 to pyran 26 with strong preference (95%) for one enantiomer. Bn (benzyl) and PMB (p-methoxybenzyl) are protecting groups that prevent alcohols from undergoing reaction. Dashed boxes represent segments of the target molecules prepared through catalytic olefin metathesis.

High resolution image and legend (143K)

In an enantioselective total synthesis of baconipyrone C68, a siphonariid (isolated from false limpets, Siphonaria baconi) metabolite (Fig. 6), the plane of symmetry within achiral 25 is removed through a ring-opening/cross metathesis with styrene promoted by chiral catalyst 6 (Fig. 2), yielding heterocycle 26 with approx95% selectivity (89% enantiomeric excess). After conversion of 26 to 27, another sequence involves conversion of 27 to 30 via 28 and 29. A ring-closing olefin metathesis, this time promoted by achiral catalyst 3 (Fig. 2), furnishes allylic alcohol 30 en route to the target.

Thus far, we have considered how, after ring-closing, ring-opening/cross or cross metathesis, olefins within the product might be masked by a subsequent reaction. The sequence in Fig. 7 illustrates a transformation that takes this 'vanishing act' to another level: although catalytic olefin metathesis is involved, neither the products nor the starting materials contain an olefin69. The alkenes needed are obtained in the course of the transformation by iridium-based catalyst 32, which converts two equivalents of the saturated hydrocarbon (alkane) 31 to two of alkene 34 by C–H activation70; this process transforms 32 to iridium-dihydride 33. Mo catalyst 1 (Fig. 1), present in the mixture, waiting for olefins to become available, connects with two molecules of 34 and transforms them to 35 and ethylene (cross metathesis). Alkene 35 can revert back to 34 after cross metathesis with ethylene, or, alternatively, its alkene may undergo isomerization to generate 36, in a reaction that is also catalysed by iridium complex 32. Alkene 36 participates in a Mo-catalysed cross metathesis with ethylene to produce two new terminal alkenes 37 and 38, which can be converted to alkanes 39 and 40 by iridium-dihydride 33, delivering back the hydrogens it borrowed from 31 to the olefins of 37 and 38. The last reaction leads to re-formation of 32 from 33, which moves on to afford alkene 34 and initiate additional cycles. One feature of this molecular choreography is that the sizeable iridium dihydride 33 deposits its two hydrogens on the terminal alkenes of 37 and 38 but not on the more hindered internal olefins of 35 or 36. On the other hand, if 33 adds its hydrogen atoms to the olefin in 34, substrate 30 is generated again and the catalytic cycle begins anew.


With a two-catalyst approach for alkane cross metathesis, will it be feasible to design a catalytic alkane ring-closing metathesis? In cases where a cycloalkane is desired, such a direct process could be more efficient than a two-step, alkene ring-closing metathesis/hydrogenation sequence. An inherent advantage of catalytic olefin metathesis is, however, the range of useful possibilities that the rich chemistry of olefins offers. Nevertheless, such considerations have led to the development of tandem catalytic reactions carried out in a single vessel, promoted by one catalyst and involving olefin metathesis reactions; Ru-catalysed olefin metathesis/hydrogenation and olefin metathesis/olefin isomerization are representative examples71.

Top

Catalytic olefin metathesis and a better quality of life

Through a select few examples (there are many more55, 72, 73, 74, 75, 76), we have seen how catalytic olefin metathesis has allowed chemists to synthesize medicinally relevant agents in entirely new ways. The utility of this class of reactions extends beyond small-scale laboratory preparation. A catalytic ring-closing metathesis promoted by catalyst 4277, a precursor to 3 (Fig. 2), has been used by scientists at Boehringer-Ingelheim to prepare multi-kilogram quantities of 43 (Fig. 8), a complex molecule that is precursor to a potent anti-hepatitis C agent78, 79, 80.

Figure 8: Catalytic olefin metathesis has been used in the large-scale preparation of pharmaceutical candidates.
Figure 8 : Catalytic olefin metathesis has been used in the large-scale preparation of pharmaceutical candidates. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

An example is the potent hepatitis C protease inhibitor BILN 2061 ZW developed by Boehringer-Ingelheim. Macrocyclic intermediate 43 has been prepared in multi-kilogram quantities as a single C = C (olefin) isomer with high efficiency.

High resolution image and legend (77K)

The influence of olefin metathesis has spread beyond biological chemistry81. Large-scale preparation of common organic feedstock chemicals and polymers is one area that has been affected. Polymers can be produced under mild conditions with commercial catalysts through ROMP processes. Commercially produced ROMP polymers include polyoctenamer (Vestenamer), polynorbornene (Norsorex) and polydicyclopentadiene82

(polyDCPD, Metathene, Metton, Pentam, Prometa, Telene). Fully hydrogenated analogues of some of these polymers are available as well; Zeonex is a saturated ROMP polymer of substituted polynorbornene.

Perhaps the most widely commercialized ROMP polymer is polydicyclopentadiene, which is prepared from endo-dicyclopentadiene—a by-product in naphtha crackers83. Various 'ill-defined' olefin metathesis catalysts are used to manufacture polydicyclopentadiene. For example, in a process that affords Telene, tetrakis(tridodecylammonium)octa-molybdate serves as a precatalyst along with the activating mixture that consists of EtAlCl2, SiCl4 and propanol. A crucial advantage of well-defined Ru-based catalysts is their high degree of polymerization, an attribute that allows for removal of the odour that emanates from the un-reacted dicyclopentadiene monomer in polydicyclopentadiene82. Polydicyclopentadiene is easily castable and mouldable by reaction injection moulding technology; moreover, owing to its durability and resistance to corrosion, polydicyclopentadiene has found a wide range of applications in heavy machinery manufacturing (for example, agricultural equipment).

Although numerous polymers are used in the manufacturing of high-end sporting and recreational goods, day-to-day items, medical instruments and electronics, and have applications in optics, access to other ROMP polymers requires development of more efficient and 'smarter' catalysts. Within this context, Chen has devised an approach to the synthesis of alternating copolymers that is based on differential reactivity of diastereomeric carbene intermediates in ROMP processes66. These transformations are promoted by complex 49, which bears a stereogenic Ru centre (hence the involvement of stereisomeric carbenes). Cyclooctene is thus co-polymerized with norbornene to afford an alternating copolymer, whereas copolymerization of these monomers under standard protocols delivers only a random copolymer. Chen's method is proof-of-principle; future research is required to address the need for active catalysts that yield a variety of alternating ROMP copolymers.

Block copolymers are poised to have a significant impact on nanotechnology. One approach to effective synthesis of these macromolecules involves ROMP processes promoted by rapidly initiating olefin metathesis catalysts. A new application for block copolymers, disclosed by General Electric, involves an inorganic-organic block copolymer of polynorbornene-decaborane as a single-source ceramic precursor, which was prepared by co-polymerization of norbornene with 6-(norbornenyl)decaborane84, 85. This copolymer was subsequently converted to nanostructured boron carbonitride and mesoporous boron nitride. In another development, Nuckolls has shown that a functionalized Ru-metal surface may catalyse olefin metathesis86. Thus, ROMP on such a surface could furnish conducting polyene nanowires.

The robustness of the ROMP polymers, and of the catalytic processes used to prepare them, has allowed the ROMP reaction to be incorporated into manufacturing methods. For example, olefin metathesis has been used in the design of self-healing materials87. Cracks, resulting from wear and tear, that appear in structural polymers can be made 'self-healing' by incorporation of small vesicles of dicyclopentadiene monomer, a highly effective ROMP substrate, within the material in question, together with small amounts of an olefin metathesis catalyst. If microcracking occurs, vesicles of monomer interact with the catalyst to elicit fast polymerization, resulting in formation of a robust polydicyclopentadiene plug in the place of the crack.

Top

Challenges that lie ahead

Many critical discoveries in catalytic olefin metathesis remain to be made. One area relates to the development of more robust yet active catalysts that are easily prepared and provide exceptional control of stereochemistry. Discovery of catalysts that allow for control of olefin stereoselectivity to obtain the thermodynamically less favoured cis disubstituted olefins, or those that promote formation of E or Z trisubstituted alkenes, is a significant challenge, and would constitute a major contribution to olefin metathesis. Identification of chiral catalysts that furnish high enantioselectivity for a range of substrates and reaction classes, such as enantioselective cross metathesis or enyne metathesis, are exciting problems that are yet to be addressed.

Although many of the transformations presented above furnish desirable products, the amount of catalyst required for an efficient, cost-effective process is too high. In certain cases, as much as 50 mol% (half the amount of the substrate) of a catalyst is needed (for example, Fig. 4): but even a 3% loading is considered excessive for a 'real-world' industrial process (for example, Fig. 8). High loadings are often the result of less than optimal catalyst lifetimes. Catalyst efficiency is, therefore, about more than simply faster rates, or high turnover frequency—it is crucial that high turnover numbers are achieved. Discovery of active and selective catalysts that are more robust will require a detailed understanding of often unexpected and abstruse deactivation pathways88.

Removal of trace metal impurities from olefin metathesis products is another complication of note, particularly in cases where compounds will be used in clinical trials. This brings us to the need for catalysts that can be easily recovered and re-used; effective catalysts bound to polymeric surfaces can minimize impurity levels and are economically attractive89, 90. In many olefin metathesis reactions that involve formation of large rings, high-dilution conditions are required, rendering the use of such processes difficult and prohibitively expensive in larger industrial-scale conditions. Catalysts designed to discourage competitive homodimerization of two substrate molecules (versus cyclization of one substrate molecule) are therefore needed.

With better catalysts, the currently untapped power of olefin metathesis will give rise to increasingly exciting applications. New-generation catalysts with improved properties are beginning to emerge. Notable examples are modified Ru catalysts 4491 and 4592 (Fig. 9), which can in some cases furnish faster reactions than the parent complex 3 (but, at times, this comes at the cost of lower catalyst stability), or those that can be used to catalyse reactions in water (46)93. Ru catalysts have been attached to sol-gel glass surfaces to give 'tablets' (47); when the tablets are placed in solution, reaction with substrates causes catalyst release, leading to efficient reactions94. The tablets can be removed simply with a pair of tweezers (no filtration and washing) and re-used up to 20 times. Catalyst 48 has been used to synthesize cyclic polymers by procedures that do not require linear precursors95. The unique features of complex 49, which, similar to 6, contains a Ru stereogenic centre, have already been discussed66. An important area of research involves development of highly reactive, but sensitive, catalysts by user-friendly in situ preparation methods that begin with relatively easy-to-handle precursors (50 and 51 to give chiral Mo catalyst 4)96.


Nature presents us with a range of architectures that are diverse in size, complexity and function. Chemical synthesis—accessing molecules revealed to us by our imagination—is crucial to our ability to produce compounds that are not found in nature, but are perhaps equally as enriching. Catalytic olefin metathesis is a component of making such dreams come true. There is, however, far more that we cannot do. The little that we can do is in need of substantial improvement. To consider catalytic olefin metathesis, or chemical synthesis, a consummated field would be akin to suggesting to Henry Ford that his model T was the be-all and end-all as far as automobiles are concerned.

Top

References

  1. Corey, E. J. The logic of chemical synthesis: Multistep synthesis of complex carbogenic molecules (Nobel Lecture). Angew. Chem. Int. Edn Engl. 30, 455–465 (1991) | Article |
  2. Meng, D. et al. Total synthesis of epothilones A and B. J. Am. Chem. Soc. 119, 10073–10092 (1997) | Article | ChemPort |
  3. Nicolaou, K. C. et al. Synthesis of epothilones A and B in solid and solution phase. Nature 387, 268–272 (1997) | Article | PubMed | ISI | ChemPort |
  4. Morrissey, S. R. NIH director has steered agency through congressional inquiries and penalty budget increases with bold actions to position agency for future. Chem. Eng. News 84 (27). 12–17 (2006)
  5. Katz, T. J. & McGinnis, J. The mechanism of the olefin metathesis reaction. J. Am. Chem. Soc. 97, 1592–1593 (1975) | Article | ChemPort |
  6. Casey, C. P. & Burkhardt, T. J. Reactions of (diphenylcarbene)pentacarbonyltungsten(0) with alkenes. Role of metal-carbene complexes in cyclopropanation and olefin metathesis reactions. J. Am. Chem. Soc. 96, 7808–7809 (1974) | Article | ChemPort |
  7. Grubbs, R. H., Carr, D. D., Hoppin, C. & Burk, P. L. Consideration of the mechanism of the metal catalyzed olefin metathesis reaction. J. Am. Chem. Soc. 98, 3478–3483 (1976) | Article | ChemPort |
  8. Schrock, R. R. Multiple metal-carbon bonds for catalytic metathesis reactions (Nobel Lecture). Angew. Chem. Int. Edn 45, 3748–3759 (2006) | Article | ChemPort |
  9. Grubbs, R. H. Olefin metathesis molecules for the preparation of molecules and materials (Nobel Lecture). Angew. Chem. Int. Edn 45, 3760–3765 (2006) | Article | ChemPort |
  10. Chauvin, Y. Olefin metathesis: The early days (Nobel Lecture). Angew. Chem. Int. Edn 45, 3740–3747 (2006) | Article | ChemPort |
  11. Trost, B. M. The atom economy — a search for synthetic efficiency. Science 254, 1471–1478 (1991) | Article | PubMed | ISI | ChemPort |
  12. Grubbs, R. H. Handbook of Metathesis (Wiley-VCH, Weinheim, 2003)
  13. Connon, S. J. & Blechert, S. Recent developments in olefin cross metathesis. Angew. Chem. Int. Edn 42, 1900–1923 (2003) | Article | ChemPort |
  14. Han, S.-Y. & Chang, S. in Handbook of Metathesis Vol. 2 (ed. Grubbs, R. H.) 5–127 (Wiley-VCH, Weinheim, 2003)
  15. Schrader, T. O. & Snapper, M. L. in Handbook of Metathesis Vol. 2 (ed. Grubbs, R. H.) 205–237 (Wiley-VCH, Weinheim, 2003)
  16. Wiberg, K. B. The concept of strain in organic chemistry. Angew. Chem. Int. Edn Engl. 25, 312–322 (1986) | Article |
  17. Conrad, J. C. et al. Oligomers as intermediates in ring-closing metathesis. J. Am. Chem. Soc. 129, 1024–1025 (2007) | Article | PubMed | ChemPort |
  18. Schrock, R. R. & Hoveyda, A. H. Molybdenum and tungsten imido alkylidene complexes as efficient olefin metathesis catalysts. Angew. Chem. Int. Edn 42, 4592–4633 (2003) | Article | ChemPort |
  19. Nguyen, S. T. & Trnka, T. M. in Handbook of Metathesis Vol. 1 (ed. Grubbs, R. H.) 61–85 (Wiley-VCH, Weinheim, 2003)
  20. Schrock, R. R. High oxidation state multiple metal–carbon bonds. Chem. Rev. 102, 145–179 (2002) | Article | PubMed | ChemPort |
  21. Katz, T. J. in Handbook of Metathesis Vol. 1 (ed. Grubbs, R. H.) 47–60 (Wiley-VCH, Weinheim, 2003)
  22. Toreki, R. & Schrock, R. R. A well-defined rhenium(VII) olefin metathesis catalyst. J. Am. Chem. Soc. 112, 2448–2449 (1990) | Article | ChemPort |
  23. Castarlenas, R., Esteruelas, M. A. & Onate, E. N-heterocyclic carbene–osmium complexes for olefin metathesis reactions. Organometallics 24, 4343–4346 (2005) | Article | ChemPort |
  24. Schrock, R. R. et al. Synthesis of molybdenum imido alkylidene complexes and some reactions involving acyclic olefins. J. Am. Chem. Soc. 112, 3875–3886 (1990) | Article | ChemPort |
  25. Scholl, M., Ding, S., Lee, C. W. & Grubbs, R. H. Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands. Org. Lett. 1, 953–956 (1999) | Article | PubMed | ChemPort |
  26. Weskamp, T., Schattenmann, W. C., Spegler, M. & Herrmann, W. A. A novel class of ruthenium catalysts for olefin metathesis. Angew. Chem. Int. Edn Engl 37, 2490–2493 (1995) | Article |
  27. Huang, J., Stevens, E. D., Nolan, S. P. & Petersen, J. L. Olefin metathesis — active ruthenium complexes bearing nucleophilic carbene ligand. J. Am. Chem. Soc. 121, 2674–2678 (1999) | Article | ChemPort |
  28. Halback, T. S. et al. Novel ruthenium-based metathesis catalysts containing electron-withdrawing ligands: synthesis, immobilization, and reactivity. J. Org. Chem. 70, 4687–4694 (2005) | Article | PubMed | ChemPort |
  29. Garber, S. B., Kingsbury, J. S., Gray, B. L. & Hoveyda, A. H. Efficient and recyclable monomeric and dendritic Ru-based metathesis catalysts. J. Am. Chem. Soc. 122, 8168–8179 (2000) | Article | ChemPort |
  30. Cortez, G. A., Schrock, R. R. & Hoveyda, A. H. Efficient enantioselective synthesis of piperidines through catalytic asymmetric ring-opening/cross-metathesis reactions. Angew. Chem. Int. Edn 46, 4534–4538 (2007) | Article | ChemPort |
  31. Slinn, C. A. et al. Synthesis of unprotected and borane-protected phosphines using Ru- and Mo-based olefin metathesis catalysts. Org. Biomol. Chem. 1, 3820–3825 (2003) | Article | PubMed | ChemPort |
  32. Jafarpour, L., Schanz, H.-J., Stevens, E. D. & Nolan, S. P. Indenylidene-imidazolidene complexes of ruthenium as ring-closing metathesis catalysts. Organometallics 18, 5416–5419 (1999) | Article | ChemPort |
  33. Barbasiewicz, M. et al. Probing of the ligand anatomy: Effects of the chelating alkoxy ligand modifications on the structure and catalytic activity of ruthenium carbene complexes. Adv. Synth. Catal. 349, 193–203 (2007) | Article | ChemPort |
  34. Stewart, I. C. et al. Highly efficient ruthenium catalysts for the formation of tetrasubstituted olefins via ring-closing metathesis. Org. Lett. 9, 1589–1592 (2007) | Article | PubMed | ChemPort |
  35. Alexander, J. B., La, D. S., Cefalo, D. S., Hoveyda, A. H. & Schrock, R. R. Catalytic enantioselective ring-closing metathesis by a chiral biphen-Mo complex. J. Am. Chem. Soc. 120, 4041–4042 (1998) | Article | ChemPort |
  36. Funk, T. W., Berlin, J. M. & Grubbs, R. H. Highly active chiral ruthenium catalysts for asymmetric ring-closing olefin metathesis. J. Am. Chem. Soc. 128, 1840–1846 (2006) | Article | PubMed | ChemPort |
  37. Van Veldhuizen, J. J., Campbell, J. E., Giudici, R. E. & Hoveyda, A. H. A readily available chiral Ag-based N-heterocyclic carbene complex for use in efficient and highly enantioselective Ru-catalyzed olefin metathesis and Cu-catalyzed allylic alkylation reactions. J. Am. Chem. Soc. 127, 6877–6882 (2005) | Article | PubMed | ChemPort |
  38. Thayer, A. Chiral catalysts. Chem. Eng. News 83, 40–48 (2005)
  39. Jacobsen, E. N., Pfaltz, A. & Yamamoto, H. Comprehensive Asymmetric Catalysis (Springer, Berlin, 1999)
  40. Hoveyda, A. H. in Handbook of Metathesis Vol. 2 (ed. Grubbs, R. H.) 128–150 (Wiley-VCH, Weinheim, 2003)
  41. Berlin, J. M., Goldberg, S. D. & Grubbs, R. H. Highly active chiral ruthenium catalysts for asymmetric cross- and ring-opening cross-metathesis. Angew. Chem. Int. Edn 45, 7591–7595 (2006) | Article | ChemPort |
  42. Giudici, R. E. & Hoveyda, A. H. Directed catalytic asymmetric olefin metathesis. Selectivity control by enoate and ynoate groups in Ru-catalyzed asymmetric ring-opening/cross-metathesis. J. Am. Chem. Soc. 129, 3824–3825 (2007) | Article | PubMed | ChemPort |
  43. Cortez, G. A., Baxter, C. A., Schrock, R. R. & Hoveyda, A. H. Comparison of Ru- and Mo-based chiral olefin metathesis catalysts. Complementarity in asymmetric ring-opening/cross-metathesis reactions of oxa- and azabicycles. Org. Lett. 9, 2871–2874 (2007) | Article | PubMed | ChemPort |
  44. Hérisson, J.-L. & Chauvin, Y. Catalyse de transformation des oléfines par les complexes du tungstène. II. Télomérisation des oléfines cycliques en présence d'oléfines acycliques. Makromol. Chem. 141, 161–176 (1971) | Article |
  45. Tallarico, J. A., Bonitatbus, P. J. & Snapper, M. L. Ring-opening metathesis. A ruthenium catalyst caught in the act. J. Am. Chem. Soc. 119, 7157–7158 (1997) | Article | ChemPort |
  46. Anderson, D. R., Hickstein, D. D., O'Leary, D. J. & Grubbs, R. H. Model compounds of ruthenium-alkene intermediates in olefin metathesis reactions. J. Am. Chem. Soc. 128, 8386–8387 (2006) | Article | PubMed | ChemPort |
  47. Poater, A., Solans-Monfort, X., Clot, E., Copèret, C. & Eisenstein, O. Understanding d0-olefin metathesis catalysts: Which metal? Which ligands? J. Am. Chem. Soc. 129, 8207–8216 (2007) | Article | PubMed | ChemPort |
  48. Sanford, M. S., Love, J. A. & Grubbs, R. H. Mechanism and activity of ruthenium olefin metathesis catalysts. J. Am. Chem. Soc. 123, 6543–6554 (2001) | Article | PubMed | ChemPort |
  49. McGuinness, D. S. & Cavell, K. J. Zerovalent palladium and nickel complexes of heterocyclic carbenes: Oxidative addition of organic halides, carbon-carbon coupling processes, and Heck reaction. Organometallics 18, 1596–1605 (1999) | Article | ChemPort |
  50. Romero, P. E. & Piers, W. E. Direct observation of a 14-electron ruthenacyclobutane relevant to olefin metathesis. J. Am. Chem. Soc. 127, 5032–5033 (2005) | Article | PubMed | ChemPort |
  51. Tsang, W. C. P. et al. Alkylidene and metallacyclic complexes of tungsten that contain a chiral biphenoxide ligand. Asymmetric ring-closing metathesis, and mechanistic investigations. J. Am. Chem. Soc. 125, 2652–2666 (2003) | Article | PubMed | ChemPort |
  52. Aldhart, C. & Chen, P. Mechanism and activity of ruthenium olefin metathesis catalysts: The role of ligands and substrates from a theoretical perspective. J. Am. Chem. Soc. 126, 3496–3510 (2004) | Article | PubMed | ChemPort |
  53. Tsang, W. P. C. et al. Investigations of reactions between chiral molybdenum imido alkylidene complexes and ethylene: Observation of unsolvated base-free methylene complexes, metalacyclobutane and metalacyclopentane complexes, and molybdenum (IV) olefin complexes. Organometallics 23, 1997–2007 (2004) | Article | ChemPort |
  54. Hoveyda, A. H. in Handbook of Combinatorial Chemistry Vol. 2 (eds Nicolaou, K. C., Hanko, R. & Hartwig, W.) 991–1016 (Wiley-VCH, Weinheim, 2003)
  55. Nicolaou, K. C., Bulger, P. G. & Sarlah, D. Metathesis reactions in total synthesis. Angew. Chem. Int. Edn 44, 4490–4527 (2005) | Article | ChemPort |
  56. Gradillas, A. & Perez-Castells, J. Macrocyclization by ring-closing metathesis in total synthesis of natural products: Reaction conditions and limitation. Angew. Chem. Int. Edn 45, 6086–6101 (2006) | Article | ChemPort |
  57. Deiters, A. & Martin, S. F. Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis. Chem. Rev. 104, 2199–2238 (2004) | Article | PubMed | ChemPort |
  58. Xu, Z. et al. Applications of Zr-catalyzed carbomagnesation and Mo-catalyzed macrocyclic ring-closing metathesis in asymmetric synthesis. Enantioselective total synthesis of Sch 38516 (fluvirucin B1). J. Am. Chem. Soc. 119, 10302–10316 (1997) | Article | ChemPort |
  59. Smith, A. B., Adams, C. M., Kozmin, S. A. & Paone, D. V. Total synthesis of (–)-cylindrocyclophanes A and F exploiting the reversible nature of olefin cross metathesis reaction. J. Am. Chem. Soc. 123, 5925–5937 (2001) | Article | PubMed | ChemPort |
  60. Nicolaou, K. C. & Sorensen, E. J. in Classics in Total Synthesis 1–19 (Wiley-VCH, Weinheim, 1996)
  61. Layton, M. E., Morales, C. A. & Shair, M. D. Biomimetic synthesis of (–)-longithorone A. J. Am. Chem. Soc. 124, 773–775 (2002) | Article | PubMed | ChemPort |
  62. Schwab, P., Grubbs, R. H. & Ziller, J. W. Synthesis and application of RuCl2( = CHR')(PR3)2: The influence of the alkylidene moiety on metathesis activity. J. Am. Chem. Soc. 118, 100–110 (1995) | Article |
  63. Katz, T. J., Lee, S. J., Nair, M. & Savage, E. B. Reactivities of metal carbenes towards alkenes and alkynes. J. Am. Chem. Soc. 102, 7942–7944 (1980) | Article | ChemPort |
  64. Katz, T. J., Savage, E. B., Lee, S. J. & Nair, M. Induction of olefin metathesis by acetylenes. J. Am. Chem. Soc. 102, 7940–7942 (1980) | Article | ChemPort |
  65. Diver, S. T. & Giessert, S. J. Enyne metathesis (enyne bond reorganization). Chem. Rev. 104, 1317–1382 (2004) | Article | PubMed | ChemPort |
  66. Bornand, M. & Chen, P. Mechanism-based design of a ROMP catalyst for sequence-selective copolymerization. Angew. Chem. Int. Edn 44, 7909–7911 (2005) | Article | ChemPort |
  67. Statsuk, A. V., Liu, D. & Kozmin, S. A. Synthesis of bistramide A. J. Am. Chem. Soc. 126, 9546–9547 (2004) | Article | PubMed | ISI | ChemPort |
  68. Gillingham, D. G. & Hoveyda, A. H. Chiral N-heterocyclic carbenes in natural product synthesis: Application of Ru-catalyzed asymmetric ring-opening/cross-metathesis and Cu-catalyzed allylic alkylation to total synthesis of baconipyrone C. Angew. Chem. Int. Edn. 46, 3860–3864 (2007) | Article | ChemPort |
  69. Goldman, A. S. et al. Catalytic alkane metathesis by tandem alkane dehydrogenation-olefin metathesis. Science 312, 257–261 (2006) | Article | PubMed | ISI | ChemPort |
  70. Labinger, J. A. & Bercaw, J. E. Understanding and exploiting C–H bond activation. Nature 417, 507–514 (2002) | Article | PubMed | ChemPort |
  71. Dragutan, V. & Dragutan, I. A resourceful new strategy in organic synthesis: Tandem and stepwise metathesis/non-metathesis catalytic processes. J. Organomet. Chem. 681, 5129–5147 (2006) | Article | ChemPort |
  72. Nickel, A. et al. Total synthesis of ingenol. J. Am. Chem. Soc. 126, 16300–16301 (2004) | Article | PubMed | ChemPort |
  73. Wipf, P. & Spencer, S. R. Asymmetric total synthesis of tuberstemonine, didehydrotuberstemonine, and 13-epituberstemonine. J. Am. Chem. Soc. 127, 225–235 (2004) | Article | ChemPort |
  74. Kinderman, S. S. et al. Aminopalladation of alkoxyallenes applied in the synthesis of an enantiopure 1-ethylquinolizidine frog alkaloid. J. Am. Chem. Soc. 126, 4100–4101 (2004) | Article | PubMed | ChemPort |
  75. Kuramochi, A., Usuda, H., Yamatsugu, K., Kanai, M. & Shibasaki, M. Total synthesis of (plusminus)-garsubellin A. J. Am. Chem. Soc. 127, 14200–14201 (2005) | Article | PubMed | ChemPort |
  76. Kummer, D. A., Brenneman, J. B. & Martin, S. F. Application of a domino intramolecular enyne metathesis/cross-metathesis reaction to the total synthesis of (+)-8-epi-xanthatin. Org. Lett. 7, 4621–4623 (2005) | Article | PubMed | ChemPort |
  77. Kingsbury, J. S., Harrity, J. P. A., Bonitatebus, P. J. & Hoveyda, A. H. A recyclable Ru-based metathesis catalyst. J. Am. Chem. Soc. 121, 791–799 (1999) | Article | ChemPort |
  78. Nicola, T., Brenner, M., Donsbach, K. & Kreye, P. First scale-up to production scale of a ring closing metathesis reaction forming a 15-membered macrocycle as a precursor of an active pharmaceutical ingredient. Org. Proc. Res. Dev. 9, 513–515 (2005) | Article | ChemPort |
  79. Poirer, M. et al. RCM of tripeptide dienes containing a chiral vinylcyclopropane moiety: Impact of different Ru-based catalysts on the stereochemical integrity of the macrocyclic products. J. Org. Chem. 70, 10765–10773 (2005) | Article | PubMed | ChemPort |
  80. Yee, N. K. et al. Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by a convergent approach based on ring-closing metathesis. J. Org. Chem. 71, 7133–7145 (2006) | Article | PubMed | ChemPort |
  81. Streck, R. Economic and ecological aspects in applied olefin metathesis. J. Mol. Catal. 76, 359–372 (1992) | Article | ChemPort |
  82. Mol, J. C. Industrial applications of olefin metathesis. J. Mol. Catal. A 213, 39–45 (2004) | Article | ChemPort |
  83. Johnson, H. F. (Standard Oil Development Co.) Cyclopentadiene. US patent 2636054. (1953)
  84. Malenfant, P. R. L., Wan, J., Taylor, S. T. & Manoharan, M. Self-assembly of an organic-inorganic block copolymer for nano-ordered ceramics. Nature Nanotechnol. 2, 43–46 (2007) | Article | ChemPort |
  85. Wei, X., Carroll, P. J. & Sneddon, L. G. New routes to organodecaborane polymers via ruthenium-catalyzed ring-open metathesis polymerization. Organometallics 23, 163–165 (2004) | Article | ChemPort |
  86. Tulevski, G. S., Myers, M. B., Hybertsen, M. S., Steigerwald, M. L. & Nuckolls, C. Formation of catalytic metal-molecule surface. Science 309, 591–594 (2005) | Article | PubMed | ChemPort |
  87. White, S. R. et al. Autonomic healing of polymer composites. Nature 409, 794–797 (2001) | Article | PubMed | ISI | ChemPort |
  88. Hong, S. H., Wenzel, A. G., Salguero, T. T., Day, M. W. & Grubbs, R. H. Decomposition of ruthenium olefin metathesis catalysts. J. Am. Chem. Soc. 127. 7961–7968 (2007)
  89. De Vos, D. E., Vankelecom, I. F. J. & Jacobs, P. A. Chiral Catalyst Immobilization and Recycling (VCH-Wiley, Weinheim, 2000)
  90. Kingsbury, J. S. & Hoveyda, A. H. in Polymeric Materials in Organic Synthesis and Catalysis (ed. Buchmeiser, M. R.) 467–502 (VCH-Wiley, Weinheim, 2003)
  91. Wakamatsu, H. & Blechert, S. A new highly efficient ruthenium catalyst. Angew. Chem. Int. Edn 41, 2403–2405 (2002) | Article | ChemPort |
  92. Grela, K., Harutyunyan, S. & Michrowska, A. A highly efficient ruthenium catalyst for metathesis reactions. Angew. Chem. Int. Edn 41, 4038–4040 (2002) | Article | ChemPort |
  93. Hong, S. H. & Grubbs, R. H. Highly active water-soluble olefin metathesis catalyst. J. Am. Chem. Soc. 128, 3508–3509 (2006) | Article | PubMed | ChemPort |
  94. Kingsbury, J. S. et al. Immobilization of olefin metathesis catalysts on monolithic sol–gel: Practical, efficient, and easily recyclable catalysts for organic and combinatorial synthesis. Angew. Chem. Int. Edn 40, 4251–4256 (2001) | Article | ChemPort |
  95. Bielawski, C. W., Benitez, D. & Grubbs, R. H. An "endless" route to cyclic polymers. Science 297, 2041–2044 (2006) | Article | ChemPort |
  96. Hock, A. S., Schrock, R. R. & Hoveyda, A. H. Dipyrrolyl precursors to bisalkoxide molybdenum olefin metathesis catalysts. J. Am. Chem. Soc. 128, 16373–16375 (2006) | Article | PubMed | ChemPort |
Top

Acknowledgements

Research in our laboratories regarding the development of catalysts for olefin metathesis has been funded by the US National Science Foundation and the US National Institutes of Health, Institute of General Medical Sciences.



http://blog.sciencenet.cn/blog-3913-10497.html

上一篇:科学家发现最短的金属-金属键
下一篇:我国发展氢能源的优劣势分析

0

发表评论 评论 (0 个评论)

数据加载中...
扫一扫,分享此博文

Archiver|手机版|科学网 ( 京ICP备07017567号-12 )

GMT+8, 2020-9-24 07:39

Powered by ScienceNet.cn

Copyright © 2007- 中国科学报社

返回顶部