Schrock catalyst molybdenum

The most widely used catalysts for RCM are Grubbs ruthenium catalyst 9 and its second generation analogue 10, as well as first and second generation Hoveyda-Grubbs catalysts 11 and 12 (Fig. 6) [38]. The latter have superior stability and reactivity, expanding the applicability of the method considerably. Schrock molybdenum catalyst 13 has also been described for macrocy-clization [38]. 

A significant development for the selective synthesis of alkenes makes use of alkene metathesis. Metathesis, as applied to two alkenes, refers to the transposition of the alkene carbon atoms, such that two new alkenes are formed (2.110). The reaction is catalysed by various transition-metal alkylidene (carbene) complexes, particularly those based on ruthenium or molybdenum. The ruthenium catalyst 84, developed by Grubbs, is the most popular, being more stable and more tolerant of many functional groups (although less reactive) than the Schrock molybdenum catalyst 85. More recently, ruthenium complexes such as 86, which have similar stability and resistance to oxygen and moisture as complex 84, have been found to be highly active metathesis catalysts. 

The basics and the synthetic potential of olefin metathesis has been recently presented in a comprehensive handbook and several reviews [58]. Thus, this chapter will be restricted to demonstrate the scope and flexibility of this type of reaction in the total synthesis of a complex natural product skeleton such as epothilone. The first total syntheses of these antitumor-active 16-membered macrolactones were based on a ringclosing metathesis (RCM) strategy (Scheme 11.36) [73]. Grubbs catalyst 143 has been used for the construction of the endocydic 1,2-disubstituted C12-C13 double bond in epothilone C 148 that, after epoxidation, affords epothilone A 150 [74]. In this approach, ruthenium carbene 143 is more efiident than Schrock molybdenum catalyst 142b [75a[. However, the RCM-route to epothilone D 149, the desoxy precursor of epothilone B 151 bearing a trisubstituted C=C bond, requires the molybdenum carbene catalyst 142b attempts to initiate ring-closure with 143 failed [75]. 

The acceptance of a (new) catalytically mediated methodology by the target-directed synthetic community strongly depends on the availability, stability, and functional group tolerance of the respective catalysts. With the commercial availability of Grubbs5 benzylidene ruthenium catalyst A [13] and Schrock s even more active, yet highly air- and moisture-sensitive molybdenum catalyst B [14]... 

The difference in reactivity is perfectly revealed in Metz s total synthesis of the molluscicidal furanosesquiterpene lactones ricciocarpin A (50) and B (51) (Scheme 9) [32]. Attempts to convert acrylate 43 to lactone 44 using Grubbs5 catalyst A or Schrock s molybdenum catalyst B resulted in very low yields of the... 

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

A year later, Schrock confirmed that the cross-metathesis of two alkyl-substituted terminal alkenes could also be catalysed by his molybdenum catalyst [26] (Eq. 9). 

Although the Grubbs ruthenium benzylidene 17 has a significant advantage over the Schrock catalyst 3 in terms of its ease of use, the molybdenum alkylidene is still far superior for the cross-metathesis of certain substrates. Acrylonitrile is one example [28] and allyl stannanes were recently reported to be another. In the presence of the ruthenium catalyst, allyl stannanes were found to be unreactive. They were successfully cross-metathesised with a variety of alkenes, however, using the molybdenum catalyst [39] (for example Eq. 20). 

It is interesting to note that the two reactions involving allyl acetate and the unprotected alcohol, but-3-en-l-ol, failed when the molybdenum catalyst was used. The failure of the Schrock catalyst to tolerate unprotected alcohols has also been observed in ring-closing metathesis [40], where a tertiary alcohol has proved to be the only success [41]. 

Alkene cross-metathesis has also been recently used for the modification of silsesquioxanes and spherosilicates, by Feher and co-workers [46]. Reaction of vinylsilsesquioxane 28 with a variety of simple functionalised alkenes, in the presence of Schrock s molybdenum catalyst 3, gave complete conversion of the starting material and very good isolated yields of the desired products (75— 100%) (for example Eq. 28). 

The molybdenum analogue of this tungsten catalyst is known as Schrock s catalyst [19]. It is less active than its tungsten counterpart, but it is much more resistant to polar groups in the substrate. 

Using 1,5-hexadiene, it was shown that, depending upon whether molybdenum- or ruthenium-based catalysts are employed, a change in mechanism appears to occur. In the presence of Schrock s molybdenum catalyst, 1,5-hexadiene produces principally linear poly(l-butenylene) [scheme (24)] [33], but with Grubbs s ruthenium catalyst the primary product is the cyclic dimer 1,5-cyclooctadiene [scheme (25)] [25,33] ... 

Most of the recent synthetic applications of M-RCM involve one of the above catalysts, particularly G1 or G2, chosen as a function of its own reactivity profile, generally after preliminary reaction assays on the genuine substrate or specific model compounds. The sensitivity of the RCM reaction to steric hindrance is well established. These ruthenium catalysts exhibit high affinity for carbon-carbon double bonds and are compatible with the presence of many functional groups, even the presence of free polar hydroxyl or amino groups. Their use does not require special conditions such as glove boxes, which are required when using Schrock s molybdenum catalyst. 

Facing the decisive ring-closure step, Schrock s molybdenum catalyst was used to promote the stereocontrolled annulative metathesis of diene 67, which ultimately yielded carbaffuctofuranose 64 after exhaustive debenzylation. 

In 2005, Piers et al. prepared the 14-electron (14e) phosphonium alkyh-dene ruthenium complex 24. This catalyst displays higher activity in the RCM of diethyl diallylmalonate at 0 °C when compared to the second generation catalyst 3 (> 90% conversion after 2 h for 24 versus 25% conversion after 4 h for 3 and > 90% after 5 h for the Schrock molybdenum-based catalyst) (Eq. 27). RCM reactions of trisubstituted, six-membered ring, or seven-membered ring substrates are catalyzed at room temperature affording good... 

This approach would neither be possible, nor conceivable, without the advent of modern olefin metathesis catalysts. Figure 3 shows a few of the most commonly used catalysts. In this work, we initially relied upon Schrock s Molybdenum catalyst 6 (7) to effect the ring closures, but now exclusively rely upon the second generation Grubbs ruthenium catalyst 7 (8). 

RCM has attracted much attention and has seen a tremendous increase in synthetic applications over the last decade <2000CR2963, 2006JOM(691)5129>. In this reaction, two C-C multiple bonds, such as double and double, or double and triple in the same molecule, are converted to unsaturated carbocycles or heterocycles in the presence of a metal carbene complex. The versatility of Schrock s molybdenum catalyst and Grubbs ruthenium complexes 68 and 69 (Scheme 10) in carbo- and heterocyclizations, respectively, of very different ring sizes were demonstrated <2000CR2963, 2006JOM(691)5129>. 

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