Self-metathesis

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-... 

In summary, the order of reactivity for the most commonly used ruthenium-based metathesis catalysts was found to be 56d>56c>9=7. This order of reactivity is based on IR thermography [39], determination of relative rate constants for the test reaction 58—>59 (Eq. 8) [40], and determination of turnover numbers for the self metathesis of methyl-10-undecenoate [43]. 

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-... 

The reversible nature of cross metathesis is of synthetic importance because, by the use of a sufficiently active metathesis catalyst, it generally ensures the preferential formation of the most thermodynamically stable product. This results in the transformation of terminal olefins into internal ones, and we have seen that undesired self-metathesis products can be recycled by exposing them to a second CM process. 

A short and efficient synthetic approach to hydroxy-substituted ( )-stil-benoids, as exemplified by the natural compound resveratrol (371b) via solid-phase CM, was reported by a Korean group (Scheme 71) [154]. When two different stilbenes were allowed to couple by catalyst C, all three kinds of possible stilbenes were obtained as an inseparable mixture. Anchoring 4-vinylphenol to Merrifield resin, followed by exposing the supported styrenyl ether 368 and diacetoxy styrene 369 (10 equiv) to the catalyst, inhibited self-metathesis of the supported substrate. Sequential separation of the homodimer formed from 369 by washing and subsequent cleavage of the resin 370 with acid provided (E)-stilbene 371a with complete stereocontrol in 61% yield. 

The effectiveness of these intermolecular reactions depends on the relative reactivity of the two components, since self-metathesis leading to dimeric products will occur if one compound is more reactive than the other. 

B. Liu and R. Roy, Olefin self-metathesis as a new entry into xenotransplantation antagonists bearing the Galili antigen, Chem. Commun. (2002) 594—595. 

Mo(CO)6/Al203 was found to be inert to self-metathesis of ethylenes... 

Self-Metathesis of Ethylenes over Re207/ A1203°... 

Allylsilanes Good Cross-/Self-Metathesis Selectivity. 162... 

Particularly noteworthy was the rhenium catalysed cross-metathesis of trans-hex-3-ene with vinyl acetate or a,p-unsaturated esters [4]. For example, crossmetathesis of methyl frans-crotonate with frans-hex-3-ene gave the desired cross-coupled product without any self-metathesis of the crotonate (Eq. 2). 

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. 

As expected, there was no formation of stilbenes or a dinitrile product and, more surprisingly, in all of the reactions reported only 5-7% of the allyltrimeth-ylsilane self-metathesis product was observed. It was proposed that this lack of allylsilane self-metathesis was due to the steric bulk of the TMS group reducing the reactivity of the Me3SiCH2 substituted alkylidene. In a more recent report by Blechert and co-workers it was noted that allyltrimethylsilane and its hydrocarbon equivalent (4,4-dimethylpent-l-ene) had comparable reactivities in the cross-metathesis reaction [28], further suggesting that the selectivity arises from steric rather than electronic effects. 

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. 

As with the allylsilane cross-metathesis reactions, significant quantities of allyl stannane self-metathesis were not detected in any of the reactions and the trans isomer predominated in the cross-metathesis products. Identical reactions were carried out using allyltributyl stannane, in place of allyltriphenyl stannane, but the yields of the cross-metathesis products were consistently lower and in many cases dropped below 25%. 

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... 

Macrocyclization of esters of allylglycine with diols has been successfully used to prepare derivatives of 2,7-diaminosuberic acid [861,864]. The latter are surrogates of cystine, and therefore of interest for the preparation of peptide mimetics. For unknown reasons protected allylglycine derivatives can not be directly dimerized by self metathesis [864]. However, catechol [864], ethylene glycol [861], and 1,2- or 1,3-di(hydroxymethyl)benzene derivatives [860] of allylglycine are suitable templates for the formal self metathesis of this amino acid via RCM. 

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]. 

Table 14.2 Comparison between silica-supported, silsesquioxane, and molecular Mo(VI) precursor as catalysts for octene and ethyl oleate self-metathesis.

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]. 

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