Schrock metathesis catalysts

Unsaturated a/r(carbosilane/siloxane) polymers have been prepared by Wagener s group by use of alicyclic diene metathesis (ADMET) reactions [4]. As shown in Figure 3, the polymer results from the formation of new C-C double bonds. Both the molybdenum and tungsten versions of the Schrock metathesis catalyst are effective [5]. 

AT-heterocyclic carbenes show a pure donor nature. Comparing them to other monodentate ligands such as phosphines and amines on several metal-carbonyl complexes showed the significantly increased donor capacity relative to phosphines, even to trialkylphosphines, while the 7r-acceptor capability of the NHCs is in the order of those of nitriles and pyridine [29]. This was used to synthesize the metathesis catalysts discussed in the next section. Experimental evidence comes from the fact that it has been shown for several metals that an exchange of phosphines versus NHCs proceeds rapidly and without the need of an excess quantity of the NHC. X-ray structures of the NHC complexes show exceptionally long metal-carbon bonds indicating a different type of bond compared to the Schrock-type carbene double bond. As a result, the reactivity of these NHC complexes is also unique. They are relatively resistant towards an attack by nucleophiles and electrophiles at the divalent carbon atom. 

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. 

Scheme 1. Metathesis catalysts introduced by Grubbs (la-b) and Schrock (2)...

Figure 16.13. Schrock-Hoveyda catalyst for asymmetric metathesis...

It is worth noting that 6,7-dihydro-2(3//)-oxepinone is an unusual lactone because it can be polymerized by two distinct mechanisms ROP of the cyclic esters by aluminum alkoxides, and the ring-opening metathesis polymerization (ROMP) of endocyclic olefins by the Schrock s catalyst (Fig. 28) [121]. 

The enantiomerically-pure intermediate 1 was prepared from the dioxolanone 4, available in three steps from L-malic acid. Lewis acid-mediated homologation converted 4, a 4 1 mixture of diastereomers, into 5 as a single diastereomer. After establishment of the alkenyl iodide, it necessary to maintain the lactone in its open form. A solution was found in the formation of the Weinreb amide. The final stereogenic center was established by Brown allylation of the derived aldehyde. The alkene metathesis to form 1 was carried out with the commercially-available Schrock Mo catalyst. The authors did not comment on the relative efficacy of alternative alkene metathesis catalysts. 

Acyclic diene metathesis (ADMET) polymerization of divinyl benzene, shown in Scheme 37, using an extremely reactive tungsten alkylidene catalyst (Schrock s catalyst) yielded PPV oligomers with DP of 8 [153]. In this example ethylene is formed as a side product of metathesis, and its removal by the use of high vacuum helps drive the polymerization in the forward direction. 

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)...

Motivated by the potential of fructose analogues as useful pharmacophores en route to allosteric modulators of phosphofructokinase-2 enzymes, Al-Abed and Seepersaud [14e] recently devised a practical, concise approach to carbafructose 64, relying on a ring closing metathesis reaction governed by Schrock s catalyst (Scheme 10). Moving from unsaturated ketose 65, easily obtained from 2,3,5-tri-O-... 

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). 

In particular, Schrock-type catalysts suffered from extreme moisture and air sensitivity because of the high oxidation state of the metal center, molybdenum. Due to the oxophilicity of the central atom, polar or protic functional groups coordinate to the metal center, poisoning the catalyst and rendering it inactive for metathesis. Since late transition metal complexes are typically more stable in the presence of a wide range of functionalities, research was focused on the creation of late transition metal carbene complexes for use as metathesis catalysts. 

These 1987 resnlts concluded that classical metathesis catalyst systems were not sufficient and that Lewis acid cocatalyst-free systems were necessary if successM ADMET condensation polymerization were to become a reality. The key to snccessM ADMET polymerization was demonstrated " nsing the Lewis acid-free tungsten alkylidene metathesis catalyst (5a), the structure of which had been reported by Schrock et just one year earlier. When this... 

Hoveyda and Schrock attached (97a) to polymer via attached styrene groups yielding the first reported supported chiral molybdenum olefin metathesis catalyst, (290) (Scheme 27). Supported complex (290) is less active than (97a), but it gives similar ranges of ees for enantioselective transformations like desymmetrization. The catalyst is recyclable and, even though the conversions have eroded, the enantioselectivity is still relatively high. Table 14. 

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