Molybdenum carbene catalysts

The drawback of the CVD method is eliminated in ROMP, which is based on a catalytic (e.g., molybdenum carbene catalyst) reaction, occurring in rather mild conditions (Scheme 2.3). A living ROMP reaction ofp-cyclophanc 3 or bicyclooctadiene 5 results in soluble precursors of PPV, polymers 4 [31] and 6 [32], respectively, with rather low polydispersity. In spite of all cis (for 4) and cis and trans (for 6) configuration, these polymers can be converted into aW-trans PPV by moderate heating under acid-base catalysis. However, the film-forming properties of ROMP precursors are usually rather poor, resulting in poor uniformity of the PPV films. 

Examples are listed in Table 8.7 for various numbers of bonds (x) between the double bonds. For the compounds with x = 6, the formation of the 7-membered ring is the preferred reaction. For x >6, the polymer is the favoured product. For x = 4 there is a remarkable variation in behaviour with the catalyst no reaction is observed with the molybdenum carbene catalyst, but with the rhodium complex there is 86% conversion of substrate in 72 h to products consisting of about 5% of cyclic dimer , 4% of cyclic trimer and 91% of linear oligomers (M = 1815). In the early stages of reaction the products are mainly the cyclic species but these undergo ROMP once their equilibrium concentration has been exceeded. With the ruthenium complex as initiator the kinetics of ROMP are less favourable and the products after 72 h consist of 25% cyclic dimer, 17% cyclic trimer and 58 % of linear oligomers (Marciniec 1995a). 

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 ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

Ring-closing metathesis is well suited for the preparation of five- or six-membered heterocycles, and has also been successfully used to prepare tetrahydropyridines on insoluble supports (Entries 1 and 2, Table 15.23). Because metathesis catalysts (ruthenium or molybdenum carbene complexes) are electrophilic, reactions should be conducted with acylated amines to avoid poisoning of the catalyst. 

Olefin metathesis is a unique reaction and is only possible by transition metal catalysis. In fact only complexes of Mo, W, Re, and Ru are known to catalyze olefin metathesis. Once it was known that metallocarbenes were the actual catalytic species, a variety of metal carbene complexes were prepared and evaluated as catalysts. Two types of catalysts have emerged as the most useful overall. The molybdenum-based catalysts developed by Schrock and ruthenium-based catalysts developed by Grubbs. 

Most of the work has been done with RUCI3, OSCI3 or IrCl3 as catalysts at 50-80 °C in water, aqueous emulsion, an aromatic solvent, or mixtures of an alcohol and water. Tungsten or molybdenum carbene complexes in toluene are effective at 20 °C with monomers that do not contain hydroxyl groups. Thus 8W (R = Me) gives polymers of very high... 

Several catalysts for ring-closing metathesis are now known. Prominent examples are shown in Scheme 1 the molybdenum carbene complex 8, introduced by Schrock et al. [4], methyltri-oxorhenium 9, discovered by Herrmann et al. [5] and the ruthenium carbene complex 10, developed by Grubbs et al. [6]... 

When coupled with living radical systems, living ringopening metathesis polymerization (ROMP) also permits the synthesis of other types of block copolymers (Figure 23) such as B-102 to B-108.67,396,397 A molybdenum carbene or ROMP intermediate is converted into a benzyl bromide-type terminal by quenching the ROMP with /> (b r omo me thy 1) b en z al d e hy d e by a retro-Wittig reaction.396 The macroinitiator thus obtained induced living radical polymerizations of styrene and MA with copper catalysts to afford B-102 to B-105. 

Apart Ifom the molybdenum carbene complexes already listed in Tables 2.1 and 2.2 Mo-based catalysts are of three main types (i) other Mo complexes, activated by a suitable cocatalyst (ii) M0CI5, also activated by a cocatalyst and (iii) supported oxides, generated in various ways. For the metathesis of terminal olefins higher than propene. Mo-based catalysts are generally more effective than the corresponding W-based catalysts. 

If the photoreduced Mo03/Si02 catalyst is treated with cyclopropane (Elev 1989a), methylcyclopropane (Vikulov 1991) or cycloheptatriene (Vikulov 1992b), followed by evacuation at 300-350°C, a much more active metathesis catalyst is obtained. Molybdenum carbenes are formed, as shown by IR and UV/vis spectroscopy (Vikulov 1989a,b), and are assumed to result from a sequence of reactions such as those shown for cyclopropane in Scheme 2.4 (Shelimov 1988 ... 

Asymmetric RCM of substituted 1,6- and 1,7-dienes, taken to partial conversion using a chiral molybdenum carbene complex as catalyst, results in residual reactant having 19-84% excess of one enantiomer (Fujimura 1996a,b). 

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