Self-metathesis, alkene

As stated above, olefin metathesis is in principle reversible, because all steps of the catalytic cycle are reversible. In preparatively useful transformations, the equilibrium is shifted to one side. This is most commonly achieved by removal of a volatile alkene, mostly ethene, from the reaction mixture. An obvious and well-established way to classify olefin metathesis reactions is depicted in Scheme 2. Depending on the structure of the olefin, metathesis may occur either inter- or intramolecularly. Intermolecular metathesis of two alkenes is called cross metathesis (CM) (if the two alkenes are identical, as in the case of the Phillips triolefin process, the term self metathesis is sometimes used). The intermolecular metathesis of an a,co-diene leads to polymeric structures and ethene this mode of metathesis is called acyclic diene metathesis (ADMET). Intramolecular metathesis of these substrates gives cycloalkenes and ethene (ring-closing metathesis, RCM) the reverse reaction is the cleavage of a cyclo-... 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

Using an equimolar quantity of allyl methyl sulphide and ds-pent-2-ene resulted in incomplete reaction of the allyl sulphide and some self-metathesis of the sulphide substrate. When an excess (4 equiv) of but-2-ene was used, however, the desired but-2-enyl sulphide was formed in a good yield at ambient temperature. In this case, the large quantities of unwanted hydrocarbon starting material and self-metathesis products were gaseous alkenes and therefore easily removed. Using a large excess of one alkene to improve the yield of the desired cross-metathesis product in this way is obviously only viable if this alkene is inexpensive and both it and its self-metathesis product are easily removed. 

Although the application of tungsten catalyst 5 to the cross-metathesis reaction of other alkenes has not been reported, Basset has demonstrated that to-un-saturated esters [18] and glycosides [21], as well as allyl phosphines [22], are tolerated as self-metathesis substrates. 

For the majority of substrates only trace amounts (<10%) of the self-metathesis products were isolated. Cross-/self-metathesis selectivity was significantly lowered, however, by the inductive effect of electron-withdrawing substituents on the alkyl-substituted alkene. Even moving a bromide one carbon closer to the double bond resulted in a significant decrease in the cross-/self-metathesis ratio (Eq.7). 

Crowe proposed that benzylidene 6 would be stabilised, relative to alkylidene 8, by conjugation of the a-aryl substituent with the electron-rich metal-carbon bond. Formation of metallacyclobutane 10, rather than 9, should then be favoured by the smaller size and greater nucleophilicity of an incoming alkyl-substituted alkene. Electron-deficient alkyl-substituents would stabilise the competing alkylidene 8, leading to increased production of the self-metathesis product. The high trans selectivity observed was attributed to the greater stability of a fra s- ,p-disubstituted metallacyclobutane intermediate. 

The two alkenes were so similar electronically and sterically, with the ester group too far away to have any affect on the double bond, that there was very little cross-/self-metathesis selectivity. An approximately statistical mixture of ester 13 and diester 14 was isolated. The high yield of the cross-metathesis product 13 obtained is due to the excess of the volatile hex-l-ene used, rather than a good cross-/self-metathesis selectivity. Although not as predominant as in the reactions involving styrene, trans alkenes were still the major products. 

Previously acrylonitrile had proved to be inert towards transition metal catalysed cross- and self-metathesis using ill-defined multicomponent catalysts [lib]. Using the molybdenum catalyst, however, acrylonitrile was successfully cross-metathesised with a range of alkyl-substituted alkenes in yields of40-90% (with the exception of 4-bromobut-l-ene, which gave a yield of 17.5%). A dinitrile product formed from self-metathesis of the acrylonitrile was not observed in any of the reactions and significant formation (>10%) of self-metathesis products of the second alkene was only observed in a couple of reactions. 

The ratio of cross-/self-metathesis products, with respect to the alkyl-substituted alkene, was generally poorer (typically 3 1) than the analogous reactions with styrene or acrylonitrile, probably due to the absence of a good alkylidene stabilising substituent on either alkene and the closer nucleophilicities of the two substrates. 

The examples listed in Table 3.21 illustrate the synthetic possibilities of cross metathesis. In many of the procedures reported, advantage is taken of the fact that some alkenes (e.g. acrylonitrile, styrenes) undergo slow self metathesis only. Interestingly, it is also possible to realize cross metathesis between alkenes and alkynes (Table 3.21, Entries 11-13), both in solution and on solid supports [927,928]. 

Catalyst IX (5 mol %) was also used for RCM or self-metathesis of different alkene derivatives. It allowed the preparation of macrocycles the nonylprodigiosin precursors and their analogs or the efficient self-metathesis of multifunctional alkene (Scheme 8.18) [62]. 

Cross-metathesis, however, is usually a nonselective reaction. Transformation of two terminal alkenes in the presence of a metathesis catalyst, for instance, can give six possible products (three pairs of cis/trans isomers) since self-metathesis of each alkene and cross-metathesis occur in parallel. It has been observed, however, that terminal olefins when cross-metathesized with styrene yield trans-P-alkylstyrenes with high selectivity.5 A useful synthetic application of cross-metathesis is the cleavage of internal alkenes with ethylene called ethenolysis to yield terminal olefins ... 

A number of new processes exploiting metathesis have been developed by Phillips. A novel way to manufacture lubricating oils has been demonstrated.145 The basic reaction is self-metathesis of 1-octene or 1-decene to produce Ci4-C28 internal alkenes. The branched hydrocarbons formed after dimerization and hydrogenation may be utilized as lubricating oils. Metathetical cleavage of isobutylene with propylene or 2-butenes to isoamylenes has a potential in isoprene manufacture.136,146 High isoamylene yields can be achieved by further metathesis of C6+ byproducts with ethylene and propylene. Dehydrogenation to isoprene is already practiced in the transformation of isoamylenes of FCC C5 olefin cuts. 

Cross-metathesis enables the efficient preparation of acyclic alkenes and 1,3-dienes on insoluble supports (Figure 5.16). Unfortunately, some types of substrate show a high tendency to yield products of self-metathesis, i.e. symmetrical internal alkenes produced by dimerization of the resin-bound alkene. This is the case, for instance, with allylglycine and homoallylglycine derivatives. Dimerization of the resin-bound alkene can, however, be effectively suppressed by reducing the loading of the support [127]. 

Polystyrene cross-linked with 1-2% DVB is sufficiently flexible to allow intermediates attached to it to react with each other. Terminal alkenes linked to this support can therefore undergo self-metathesis to yield symmetrical, internal alkenes when treated with a suitable catalyst [133,134]. Self-metathesis of support-bound /V-alke-noylated peptides has been used by Conde-Frieboes et al. [133] for the preparation of symmetrical peptidomimetics (Figure 5.17). Various peptides were prepared on cross-... 

Dimethylbut-l-ene (neohexene), which is inactive to self-metathesis, undergoes cross-metathesis with internal alkenes to high conversion when catalysed by WCl6/Et20/Bu4Sn153. 

Cross-metathesis of equimolar amounts of styrene with symmetrical alkenes occurs on Re207/Al2C>3 at 50 °C. 85-90% of the styrene is converted to 1-phenylalk-l-enes and only 10% to the self-metathesis product stilbene171. Likewise, the reaction of styrene with 0.5 equiv oct-l-ene catalysed by 8 gives >85% of the cross-metathesis product (>95% trans) and <4% of the self-metathesis product of oct-l-ene172. 

Metathesis of alkenes has been reviewed in terms of cross-metathesis, ring opening and closing, disproportionation, transmutation, and self-metathesis.34 A review on catalytic processes involving ft -carbon elimination has summarized recent progress on palladium-catalysed C-C bond cleavage in various cyclic and acyclic systems.35... 

Metathesis is a versatile reaction applicable to almost any olefinic substrate internal, terminal or cyclic alkenes, as well as dienes or polyenes. (Alkyne metathesis is a growing area, but will not be dealt with here.) The reaction is also known as olefin disproportionation or olefin transmutation, and involves the exchange of fragments between two double bonds. Cross metathesis (CM, Figure 1) is defined as the reaction of two discrete alkene molecules to form two new alkenes. Where the two starting alkene molecules are the same it is called self-metathesis. Ethenolysis is a specific type of cross metathesis where ethylene... 

The metathesis of unsaturated fatty-acid esters has received considerable attention. Aspects of the metathesis of fatty-acid esters and related compounds were recently reviewed by Boelhouwer.With the WCl6/Me4Sn system, both self-metathesis and co-metathesis (with symmetric alkenes) of unsaturated esters occur, provided that the double bond and the ester group are separated by at least one methylene group.As an example, conversion of C8-C=C-C7-COOC of 50% for self-metathesis and 70% for co-metathesis... 

A general problem of alkene cross-metathesis is the formation of self-condensation products from the starting alkenes. On the solid phase, dimerization of polymer-bound alkene should be miniinized by the use of excess alkene in solution combined with the effective dilution of the resin-bound alkene by site isolation effects (see Suzuki coupling). Homocoupled products of the solution phase alkene are simply washed way during the resin washes. 

The main limitation in the broad apphcation of alkene cross-metathesis reactions in the synthesis of unsaturated compounds is the formation of self-coupling byproducts. Moreover, these impurities, frequently difficult to separate, are usually formed alongside the desired compound in an almost statistical ratio. Another issue associated with this kind of reaction is the stereocontrol of fhe newly formed double bond. 

Metathesis has been applied in oleochemistry for many years, but only fairly recently technical realization comes within reach [33, 34]. As typical catalysts, ruthenium carbene complexes of the Grubbs type are applied because of their very high activity (turnover numbers up to 200 000). In principle, oleochemical metathesis can be divided into two different types in self-metathesis the same fatty substrate reacts with itself and in cross-metathesis a fatty substrate reacts with, for example, a petrochemical alkene. The simplest case, the self-metathesis of methyl oleate forms 9-octadecene and dimethyl 9-octadecenedioate. The resulting diester can be used along with diols for the production of special, comparatively hydrophobic, polyesters. An interesting example of cross-metathesis is the reaction of methyl oleate with an excess of ethene, so-called ethenolysis. This provides two produds, each with a terminal double bond, 1-decene and methyl 9-decenoate (Scheme 3.3). 

The cis isomer of 9-tricosene is the sex pheromone of Musca domestica (housefly). It should be noted that cross-metathesis reactions involving unsymmetrical internal alkenes can lead to a complex product mixture, as self-metathesis and other cross-metathesis reactions also occur. 13-Heptacosene, the cis form of... 

Cross-metathesis of two different alkenes to give an acyclic alkene is complicated by the possible formation of not only the desired cross-metathesis product, but also self-metathesis products, each as a mixture of alkene isomers. However, some alkenes are amenable to efficient cross-metathesis to give the desired substituted alkene. This is particularly the case with alkenes that are slow to homod-imerize, such as a, -unsaturated carbonyl compounds or alkenes bearing bulky substituents. Hence, cross-metathesis of methyl acrylate with an alkene proceeds efficiently (2.116). The ruthenium catalyst reacts preferentially with the more electron-rich alkene 98, which then undergoes cross-metathesis with the acrylate or self-metathesis with another molecule of the alkene 98. The latter reaction is reversible and hence a high yield of the desired substituted acrylate results over time. The use of 1,1-disubstituted alkenes as partners in cross-metathesis provides a route to trisubstituted alkenes. This chemistry is therefore a useful alternative to conventional syntheses of alkenes, such as by the Wittig reaction. 

These desymmetrisations by CM are challenging because selectivity has to be controlled at several levels. There are many alkenes in the reaction mixture that can undergo undesired self-metathesis reactions. In addition, double metathesis yielding achiral products has to be minimised. Finally, there is the issue of EjZ selectivity. Despite these hurdles, several examples of F-stereogenic (but racemic) phosphine oxides 115 were obtained from prochiral phenyl divinylpho-sphine oxide (114) in 47 6% yield. A three-fold excess of 114 was used to minimise double metathesis. In all but one case none of the E isomer of 115 is formed. The vinyl group in 115 was further functionalised by CM with styrene. 

Vilar and coworkers [59] have investigated the use of additives to suppress olefin migration in the self-metathesis of urea derivatives (Scheme 12.33). The Af-allyl urea 109 was found to undergo self-metathesis in the presence of Ru catalyst 3 in 33% yield. The isomerized species 110 was isolated as the major product (55% yield, Z= 1 1). Vilar and coworkers identified phenylphosphoric acid (112) as an effective inhibitor of the undesired alkene isomerization. When the metathesis of Af-allyl urea 109 was performed with phenylphosphoric acid (50mol%), the desired dimer 111 was isolated in 56% yield, and 30% of the starting material 109 could be recovered. The authors also investigated the use of benzoquinone derivatives, and found that 2,6-dichloro-l,4-benzoquinone (10 mol%) was equally... 

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