Schrock tungsten

Fig. 3 Olefin metathesis catalysts Schrock tungsten (Cl) and molybdenum (C2) alkylidene complexes, Grubbs first- (C3) and second-generation (C4) catalysts, Hoveyda-Grubbs second-generation catalyst (C5), and Grubbs third-generation catalyst (C6)...

Cruentaren A 3 has two Z alkenes, so the authors chose a bis-alkyne strategy, with a partial hydrogenation of both alkynes at the end of the synthesis. To this end, alkyne metathesis was accomplished with the Schrock tungsten carbine catalyst 13. Homologation to 15 followed by deprotection and hydrogenation then gave enantiomerically pure cruentaren A3. 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

These limitations were overcome with the introduction of the well-defined, single-component tungsten and molybdenum (14) alkylidenes in 1990. (Fig. 8.4).7 Schrock s discoveiy revolutionized the metathesis field and vastly increased die utility of this reaction. The Schrock alkylidenes are particularly reactive species, have no side reactions, and are quite effective as polymerization catalysts for both ROMP and ADMET. Due to the oxophilicity of molybdenum, these alkylidenes are moisture and air sensitive, so all reactions using these catalysts must be performed under anaerobic conditions, requiring Schlenk and/or glovebox techniques. 

Schrock RR (1998) Olefin Metathesis hy Well-Defined Complexes of Molybdenum and Tungsten. 1 1-36... 

In marked contrast to the results of Gassman and Schrock, major differences were noted by Casey and co-workers in a series of studies utilizing phenylcarbene-substituted W(0) complexes in reactions with olefins. The H NMR spectra of new phenylcarbene tungsten and iron (69) complexes indicate a substantial positive charge residing on the carbene carbon, and as expected, these complexes readily form ylides on reaction with phosphines ... 

Initial reports of cross-metathesis reactions using well-defined catalysts were limited to simple isolated examples the metathesis of ethyl or methyl oleate with dec-5-ene catalysed by tungsten alkylidenes [13,14] and the cross-metathesis of unsaturated ethers catalysed by a chromium carbene complex [15]. With the discovery of the well-defined molybdenum and ruthenium alkylidene catalysts 3 and 4,by Schrock [16] and Grubbs [17],respectively, the development of alkene metathesis as a tool for organic synthesis began in earnest. 

Metal alkylidene complexes find application in the metathesis of alkenes, the cvclopropanation of alkenes (Grubbs, Schrock), Wittig type reactions, and the McMurry reaction. In suitable complexes a-elimination can occur twice yielding alkylidync complexes. See Figure 2.21 for an example with tungsten. 

Probably the first isolated tungsten alkylidene complex active in metathesis and completely characterised is the one shown in Figure 16.10 reported by Wengrovius and Schrock the analysis included an X-ray structure determination by Churchill and co-workers [18], The alkylidene was transferred from a tantalum complex to yield the hexacoordinate tungsten complex containing two PEt3 ligands. One of these can be removed by the addition of half an equivalent of palladium chloride. The total turnover number of these catalysts with Lewis acids added was 50 in 24 hours. 

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. 

The molybdenum complex 1, a typical high-valent Schrock-type carbene, efficiently catalyzes the self-metathesis of styrene. On the other hand, the cationic iron complex 3 does not induce metathesis but stoichiometrically cyclopropanates styrene. The tungsten complex 2, again a Fischer-type carbene complex, mediates... 

Schrock and coworkers have generated and tested more than forty molybdenum and tungsten imido complexes with pincer iridium complex for AM [59]. In general, tungsten complexes perform better than molybdenum complexes, presumably due to... 

At the same time, Filrstner used tungsten alkyUdene complex 150 developed by Schrock for ring-closing alkyne metathesis. He compared the reactivities of tungsten alkylidyne complex 150 and Mo(CO)6-p-ClC6H40H (Table 6.4) and showed that both catalysts work well, although a higher reaction temperature is required in the case of Mo(CO)6-p-chlorophenol. 

Better control of the reaction is achieved by using stable, isolable metal-carbene complexes, such as the Schrock initiators based on molybdenum and tungsten (LXIV, Mt = W, Mo) and the Grubbs initiators based on mthenium (LXV). The Schrock initiators... 

This mechanism was later confirmed experimentally in 1981 by Schrock and others, who reported the first example of alkyne metathesis by tungsten(vi)-alkylidyne complex. They have prepared tungsten alkylidyne complex 120 (Equation (21)) and found that it reacts with diphenylacetylende to give tungsten alkylidyne complex 121 and another alkyne 122 (lequiv.) (Equation (22)). Furthermore, complex 121 works as a catalyst for the alkyne metathesis reaction. 

At the same time, Fiirstner and others used Schrock s tungsten alkylidyne complex 120 for ring-closing alkyne metathesis. They compared 120 with the Mo(CO)6-/>-ClC6H40H system (Table 4) in reactivity and found that... 

The breakdown of metal-metal bonds without changes in the oxidation state. The processes of this kind have been first discovered by Schrock et al. in the course of investigation of the mechanisms of the catalytical action of low-valent tungsten alkoxocomplexes in the reaction of olefine metathesis [349,1017] ... 

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