Metathesis terminal alkenes

The metathesis concept on a solid support has been extended to so-called crossmetathesis, whereby one of the reacting alkenes is attached to the solid support and a terminal alkene is present in solution [138], During metathesis, this terminal alkene becomes immobilized on the resin. The reaction conditions were optimized in such a way that the possible formation of macrocycles could be prevented. The allyl-dimethylsilyl polystyrene 116 used in the reaction was synthesized according to Scheme 55. After metathesis, terminal alkenes 117 are released by scission of the Si-C bond mediated by appropriate nucleophiles (Sakurai conditions). 

Alkene metathesis (or olefin metathesis) breaks the double bond of an alkene and then rejoins the fragments. When the fragments are joined, the new double bond is formed between two sp carbons that were not previously bonded. Alkynes also undergo metathesis. Terminal alkenes give the best yield of a single alkene product in metathesis because one of the products is ethene, which can be easily removed from the reaction mixture, thus shifting the equilibrium in favor of the other new alkene product. 

A year later, Schrock confirmed that the cross-metathesis of two alkyl-substituted terminal alkenes could also be catalysed by his molybdenum catalyst [26] (Eq. 9). 

The success of the cross-metathesis reactions involving styrene and acrylonitrile led to an investigation into the reactivity of other Ji-substituted terminal alkenes [27]. Vinylboranes, enones, dienes, enynes and a,p-unsaturated esters were tested, but all of these substrates failed to undergo the desired cross-metathesis reaction using the molybdenum catalyst. 

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... 

Reaction of this same cyclobutene substrate 48 with a terminal alkene (TB-DMS protected pent-4-en-l-ol) gave a good yield (84%) of the cross-metathesis products, but with very little regioselectivity (3 2 mixture of regioisomers). 

Scheme 2. Catalytic cross-metathesis binding of terminal alkenes (A) and alkynes (B) to allyldimethylsilyl polystyrene.

Olefin metathesis enables the catalytic formation of C=C double bonds under mild conditions.1 After the development of well-defined catalysts,1 2 selective cross-couplings between functionalized terminal alkenes (CM) have been noted.2 A general problem... 

Only recently a selective crossed metathesis between terminal alkenes and terminal alkynes has been described using the same catalyst.6 Allyltrimethylsilane proved to be a suitable alkene component for this reaction. Therefore, the concept of immobilizing terminal olefins onto polymer-supported allylsilane was extended to the binding of terminal alkynes. A series of structurally diverse terminal alkynes was reacted with 1 in the presence of catalytic amounts of Ru.7 The resulting polymer-bound dienes 3 are subject to protodesilylation (1.5% TFA) via a conjugate mechanism resulting in the formation of products of type 6 (Table 13.3). Mixtures of E- and Z-isomers (E/Z = 8 1 -1 1) are formed. The identity of the dominating E-isomer was established by NOE analysis. 

The treatment of equivalent amounts of two different alkenes with a metathesis catalyst generally leads to the formation of complex product mixtures [925,926]. There are, however, several ways in which cross metathesis can be rendered synthetically useful. One example of an industrial application of cross metathesis is the ethenolysis of internal alkenes. In this process cyclic or linear olefins are treated with ethylene at 50 bar/20 80 °C in the presence of a heterogeneous metathesis catalyst. The reverse reaction of ADMET/RCM occurs, and terminal alkenes are obtained. 

One special case of cross metathesis is ring-opening cross metathesis. When strained, cyclic alkenes (but not cyclopropenes [818]) are treated with a catalytically active carbene complex in the presence of an alkene, no ROMP but only the formation of monomeric cross-metathesis product is observed [818,937], The reaction, which works best with terminal alkenes, must be interrupted when the strained cycloalkene is consumed, to avoid further equilibration. As illustrated by the examples in Table 3.22, high yields and regioselectivities can be achieved with this interesting methodology. 

The cross-metathesis of terminal alkenes and functionalized alkenes is shown in Table 6.2. In each case, a CM product is obtained in high yield and an -isomer is formed predominantly. ... 

Diyne-ene metathesis has also been reported. The reaction of diyne-ene 133a with Ic in the presence of terminal alkene gives triene 134a [Eq. (6.103)]. Intramolecular diyne-ene metathesis gives tricyclic compounds 134b... 

Blechert et al. succeeded in intermolecular CM of terminal alkyne and terminal alkene. A reaction carried out in CH2CI2 at RT in the presence of 5-7mol% Ic gives a mixture of ( )- and (Z)-isomers (Table 2). Because of the nonselective stereochemical course, a silyl-protected ally alcohol is employed and the resulting metathesis product is deprotected and oxidized to afford the desired diene having an -configuration (Equation (13)). 

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 ... 

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. 

For the cleavage of alkenes from a support by metathesis, several strategies can be envisaged. In most of the examples reported to date, ring-closing metathesis of resin-bound dienes has been used to release either a cycloalkene or an acyclic alkene into solution (Figure 3.38, Table 3.44). Further metathesis of the products in solution occurs only to a small extent when the initially released products are internal alkenes, because these normally react more slowly with the catalytically active carbene complex than terminal alkenes. If, however, terminal alkenes are to be prepared, selfmetathesis of the product (to yield ethene and a symmetrically disubstituted ethene) is likely to become a serious side reaction. This side reaction can be suppressed by conducting the metathesis reaction in the presence of ethene [782,783]. 

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-... 

As the above studies predicate, reaction of 18 is significantly less efficient with 11a (<5% conversion in 18 h) and that of 20 proceeds only to 50% conversion in 24 h in the presence of 4a (65% ee). Remarkably, in the latter transformation, even in a 0.1 M solution, the major product is the homodimer formed through metathesis of the terminal alkenes. The absence of homodimer generation when 1 la is used as the catalyst, particularly in the absence of any solvent, bears testimony to the high degree of catalyst-substrate specificity in these catalytic C-C bond-forming reactions. 

With terminal alkenes, degenerate metathesis (equation 13), competes with productive metathesis (equation 14), to an extent which depends very much on the catalyst. 

Reaction of the complex 24 with terminal alkene 25 generates styrene and the real catalytic species 27 via the ruthenacyclobutane 26. The complex 24 is commercially available, active without rigorous exclusion of O2 and water, and has functional group tolerance. Carbonyl alkenation is not observed with the catalysts 22 and 24. Their introduction has enormously accelerated the synthetic applications of alkene metathesis [11]. 

Cross-metathesis of two different alkenes 11 and 42 usually produces a mixture of products 6 and 15. However, depending on the functional groups R1 and R2, the cross-product 6 is obtained with high selectivity rather than the homoproduct 15 from 11 and 42. Some terminal alkenes, such as allylstannane [16], acrylonitrile [17,18] and allylsilane [19], undergo clean cross-metathesis to give cross-products 6 as the main product, rather than homoproducts 15. Cross-metathesis of the cyclic alkenes 43 with terminal alkenes 42 can be used for the synthesis of dienes 44. 

A very useful cross-metathesis is the reaction involving ethylene, which is called ethenolysis. Reaction of ethylene with internal alkenes produces the more useful terminal alkenes. Two terminal alkenes 45 and 42 are formed from the unsymmetric alkene 6 and ethylene. The symmetric alkenes 11 are converted to single terminal alkenes 45. The terminal dienes 46 are formed by ethenolysis of the cyclic alkenes 43. 

The complex WOCI4—Cp2TiMe2 was used for the metathesis of ethyl oleate (51) to give diethyl 9-octadecenedioate (52). Civetone (53) was synthesized by the Dieckmann condensation of this diester, followed by decarboxylation [20], Homometathesis of terminal alkenes is useful, because it yields symmetric internal alkenes and ethylene, which can be removed easily. Metathesis of 10-undecenoate (54) proceeds smoothly to give the diester 55 [20],... 

Cross-metathesis using terminal alkenes or ethylene... 

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