Simple cross-metathesis

Most of the experimental values of r and hence of must be regarded as 

In cross-metathesis with symmetrical olefins only a single series of telomers can be formed. The transfer constants can then be determined directly from the relative rates of consumption of cyclic and linear olefins, making allowance for back reactions. For the cross-metathesis of cyclooctene with internal olefins, catalyzed by WCl6/Me2Si(CH2SiMe2CH2), Korshak (1982) obtained the following values for the transfer constants cw-but-2-ene 0.9, trans-but-2-ene 0.6, rra 5-oct-4-ene 0.2. 

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The first reaction where Z selectivity was demonstrated with both MoAXi and Ru catalysts was the simple cross metathesis of one olefin substrate with itself to give the internal olefin dimer (e.g.. Figure 3.2). With Ru catalysts, high loadings (about 5 mol%) were initially required, but these have since been decreased to as low as 0.01 mol%. For the most part, only simple olefin substrates, such as... 

The use of ill-defined catalysts for the cross-metathesis of allyl- and vinylsi-lanes has also received considerable attention, particularly within the past decade. Using certain ruthenium catalysts, allylsilanes were found to isomerise to the corresponding propenylsilanes prior to metathesis [5]. Using rhenium- or tungsten-based catalysts, however, successful cross-metathesis of allylsilanes with a variety of simple alkenes was achieved [6,7] (an example typical of the results reported is shown in Eq. 3). 

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. 

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). 

In 1995 the first examples of ring-opening cross-metathesis reactions for the preparation of functionalised monomeric products using the Grubbs ruthenium vinylalkylidene catalyst 4 were published by Snapper and co-workers [47]. Reaction of a variety of symmetrical cyclobutenes with simple terminal alkenes... 

Tebbe and co-workers reported the first olefin metatheses between titanocene-methyli-dene and simple terminal olefins [13]. They showed cross-metathesis between isotopically labeled isobutene and methylenecyclohexane to be catalyzed by titanocene-methylidene. This process is referred to as degenerate olefm metathesis as it does not yield any new olefin (Scheme 14.6). The intermediate titanacyclobutane has been isolated and characterized [14], and its stability [15] and mechanism of rearrangement [16] have been investigated. 

As described above in Eq. 43, simple allylboronates can be transformed into more elaborated ones using olefin cross-metathesis. " Treatment of pinacol allylboronate 31 with a variety of olefin partners in the presence of Grubbs second-generation catalyst 142 smoothly leads to formation of 3-substituted allylboronates 143 as cross-metathesis products (Eq. 104). Unfortunately, these new allylic boronates are formed as mixtures of geometrical isomers with modest E/Z selectivity. They are not isolated but rather are treated directly with benzaldehyde to give the corresponding homoallylic alcohol products in good yields (Table A). 

A major objection to these mechanisms was raised by Herisson and Chauvin,64 who found that cross-metathesis between a cycloalkene and an unsymmetric alkene resulted in a statistical distribution of cross-products even at very low conversion, whereas a simple pairwise mechanism would lead to a single product. It is also important to point out that cyclobutanes are not isolated as intermediates and are unreactive under metathesis conditions.30... 

The trend of structural selectivity can be summarized as degenerate metathesis of terminal alkenes (exchange of methylene groups) > cross-metathesis of terminal and internal alkenes > metathesis of internal alkenes > productive metathesis of terminal alkenes (formation of internal alkene and ethylene).87 Since different catalyst systems exhibit different selectivities, a simple general picture accounting for all stereochemical phenomena of metathesis is not feasible. 

Cross-metathesis applications, 11, 200 enynes, 11, 282 in ethenolysis, 11, 198 Lewis-basic substrates, 11, 193 in one-pot reactions, 11, 197 for reagent synthesis, 11, 188 as simple metathesis reaction, 1, 171 Crotyltributyltins, with aldehydes, 9, 352 Crown ether clathrates, diorganozinc compounds, 2, 335 Crown ether-pendant polysilanes, preparation, 3, 577 Crown-ethers, as hosts, 12, 813... 

RCM and CM provide convenient access to a range of intricate products of relevance to the pharmaceutical, agrochemical and fragrance industries. While RCM can effectively create the functionalized carbo- and hetero-cyclic structures common in many such products, cross metathesis is a simple way of introducing often difficult combinations of functional groups. 

Ring closing and cross metathesis allow the rapid synthesis of simple cyclic and acyclic systems. The metathesis activity that is now possible using well-defined catalysts allows for the rapid generation of complexity from simple starting materials by relay processes and combinations of metathesis steps. Many of these reactions have been recognized only recently, are now beginning to be used in complex synthetic transformations. A few of these types of reactions will be outlined here to demonstrate the power of these multistep, relay processes. In these processes, an initial metathesis step leads to a new carbene that results in further transformations of the substrate. 

The amine 49, made from one enantiomer of propylene oxide by simple reactions, is the source of the chirality. A cross-metathesis with 47, using the Grubbs catalyst 50 gave a surprisingly excellent yield (89%) of the complete carbon skeleton 49 of monomorine. 

Derivatives of oleic acid that imdergo cross-metathesis with simple olefins are listed in Table 9.4, while Table 9.5 gives some examples of cross-metathesis reactions of simple olefins with other functional olefins. Such cross-metathesis reactions may provide useful routes to speciality chemicals such as synthetic perfumes, insect pheromones (Crisp 1988), prostaglandin intermediates (Dalcanale 1985), etc. (see Mol 1982, 1991). Of special interest are ethenolysis reactions, which allow the synthesis of compoimds with terminal double bonds. Ethenolysis (and cross-metathesis with lower olefins) has been investigated extensively for... 

Table 9.4 Examples of cross-metathesis reactions of oleic acid and its derivatives with simple olefins... 

The general reaction equation for alkene metathesis in a simple system, cross-metathesis of two different disubstituted alkenes, is depicted in Scheme 1. In this reaction, a transition metal catalyst establishes equilibrium between the starting alkenes, the ( )- and (Z)-stereoisomers of all possible substituent combinations, and ethylene. Related reaction processes have also been reported for alkynes (aikyne metathesis) and for combinations of alkenes and alkynes (enyne metathesis). Aikyne metathesis is less well developed compared to alkene metathesis and enyne metathesis. This review has been organized according to the basic modes of metathesis depicted in Scheme 2. Alkene metathesis is the more developed process and numerous examples of all the variants have been reported. Aikyne metathesis is less well developed and three variants exist aikyne cross-metathesis, aikyne metathesis polymerization, and ring-closing aikyne metathesis. 

Treatment of an alkyne/alkene mixture with ruthenium carbene complexes results in the formation of diene derivatives without the evolution of byproducts this process is known as enyne cross-metathesis (Scheme 22). An intramolecular version of this reaction has also been demonstrated, sometimes referred to as enyne RCM. The yield of this reaction is frequently higher when ethylene is added to the reaction mixture. The preferred regiochemistry is opposite for enyne cross-metathesis and enyne RCM. The complex mechanistic pathways of Scheme 22 have been employed to account for the observed products of the enyne RCM reaction. Several experiments have shown that initial reaction is at the alkene and not the alkyne. The regiochemistry of enyne RCM can be attributed to the inability to form highly strained intermediate B from intermediate carbene complex A in the alkene-first mechanism. Enyne metathesis is a thermodynamically favorable process, and thus is not a subject to the equilibrium constraints facing alkene cross-metathesis and RCM. In a simple bond energy analysis, the 7r-bond of an alkyne is... 

From a synthetic point of view, cross-metathesis reactions are very useful for the production of fine chemicals, which often can hardly be obtained by other means. An example is the synthesis of 1-triacontanol, CH3(CH2)28CH20H, a plant growth stimulant. This synthesis was performed in a relatively simple two-step process by cross-metathesis of methyl erucate with 1-octadecene in the presence of a WCl6/Me4Sn catalyst, equation (7), followed by hydrogenation over a Cu/Zn catalyst of the ester thus obtained [14]. 

In other circumstances, the failure of an RCM reaction may lead to dimerization. As many natural products are dimers, this can be useful for their synthesis. This approach was used to prepare the cylindrocyclophanes 8.271 (Scheme 8.73). - The diene starting material 8.269 could not undergo simple RCM due to thepara-disubstituted aromatic ring. Instead, a cross-metathesis (see below) occurred, followed by a macrocyclic RCM to give 8.270. The natural product 8.271 could then be obtained by reduction of the two alkenes and deprotection. 

Chauvin and Herisson found in 1970, that the initial product distribution in the cross metathesis of cyclopentene and 2-pentene is not in accordance with such a simple pairwise mechanism [30,50]. Therefore, they proposed a novel non-pairwise mechanism with metal carbene complexes as intermediates (5) [50]. 

Velder, J., Ritter, S., Lex, J., Schmalz, H.-G., A simple access to biologically important trans-stilbenes via Ru-catalyzed cross metathesis. Synthesis 2006, 273-278. 

As described in Section 6.2.2.6, simple allylboronates can be elaborated into more substituted ones using olefin cross-metathesis (Table 6.1) [82]. In the work of Goldberg and Grubbs, treatment of pinacol allylboronate 2 with various olefin parmers (104) in the presence of catalyst 63 smoothly leads to formation of a 3-substituted allylboronate, the cross product 105 (Equation 51). This new boronate is not isolated but rather is treated directly with benzaldehyde to give the homoallylic alcohol product 106 in good yield. 

It was thought that a new type of analog that does not contain the endocyclic double bond could be synthesized in almost exactly the same manner. Instead of the mono-esterified pimelic acid undergoing the aldol reaction with acrolein, an allyl group could be installed via a simple enolate alkylation reaction. Subsequent methylation, elimination, decarboxylation, cycloaddition, and cross-metathesis steps could be performed in the same manner as before with the result being a more saturated analog (76 Scheme 15). The synthesis to generate diester 73 proceeded as planned however, numerous decarboxylation conditions failed. 

For the synthesis of the central C22-C23 alkene of the side chain 79, a challenging cross-metathesis approach was evaluated. This would allow for a modular and simple modification at this part of the natural product (Scheme 16). 

Lesma and associates began their synthesis of (-b)-monomorine I (1562) with the N-Boc -protected amine 1623, a simple derivative of (5)-pyroglu-tamic acid (Scheme 205). Reaction with allyltrimethylsilane in the presence of boron trifluoride according to a reported procedure and replacement of the Boc group by Cbz produced the 2,5-n s-disubstituted pyrrolidine (—)-1624, cross-metathesis of which with methyl vinyl ketone... 

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