Styrenes cross-metathesis

The tandem use of asymmetric allylboration to give enantiomerically pure ho-moallyHc alcohols followed by cross-metathesis of homoallylic silyl ethers with p-substituted styrenes has been reported [120] (Eq. 19). Exclusively trans cross-coupled products were formed in 50-75% yields. 

The reaction tolerated a variety of functionality, including ester and ether groups on the alkyl-substituted alkene at least two carbons away from the double bond, and raefa-nitro or para-methoxy substituents on the styrene. As expected, cross-metathesis occurred selectively at the less hindered monosubsti-tuted double bond of dienes also containing a disubstituted alkene (Eq. 8). 

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. 

Like styrene, acrylonitrile is a non-nucleophilic alkene which can stabilise the electron-rich molybdenum-carbon bond and therefore the cross-/self-metathe-sis selectivity was similarly dependent on the nucleophilicity of the second alkene [metallacycle 10 versus 12, see Scheme 2 (replace Ar with CN)]. A notable difference between the styrene and acrylonitrile cross-metathesis reactions is the reversal in stereochemistry observed, with the cis isomer dominating (3 1— 9 1) in the nitrile products. In general, the greater the steric bulk of the alkyl-substituted alkene, the higher the trans cis ratio in the product (Eq. 11). 

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. 

Cross-metathesis reactions with styrenes or acrylonitrile gave yields and cist trans selectivities that were comparable with the best results obtained in the previous reports (for example Eq. 12). 

During the past 2 years several research groups have published research that either uses or expands upon Crowe s acyclic cross-metathesis chemistry. The first reported application of this chemistry was in the synthesis of frans-disubstitut-ed homoallylic alcohols [30]. Cross-metathesis of styrenes with homoallylic silyl ethers 15, prepared via asymmetric allylboration and subsequent alcohol protection, gave the desired trans cross-metathesis products in moderate to good yields (Eq. 15). 

Barrett and Gibson also reported the application of the molybdenum catalysed cross-metathesis reaction to the elaboration of (3-lactams [31,32]. Protected allyloxy p-lactams 16 were successfully cross-metathesised with a selection of substituted styrenes to yield trans cross-metathesis products (Eq. 16). 

It is worth noting that the reactions with the unsubstituted styrene gave noticeably higher yields than the corresponding cross-metathesis reactions with the substituted styrenes. This appears to be quite a common characteristic of the molybdenum catalysed cross-metathesis reaction. 

About the same time, we published our own results on the cross-metathesis of the amino acid homoallylglycine using the Grubbs ruthenium catalyst 17 [42]. Both styrene and oct-l-ene were successfully cross-metathesised with protected homoallylglycine to give the desired products in moderate to good yields (Eq. 24). 

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]. 

A Wang-supported Styrene Ether Catalyst for Stereoselective Cross Metathesis... 

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 chiral Mo-alkylidene complex derived from AROM of a cyclic olefin may also participate in an intermolecular cross metathesis reaction. As depicted in Scheme 16, treatment of meso-72a with a solution of 5 mol % 4a and 2 equivalents of styrene leads to the formation of optically pure 73 in 57% isolated yield and >98% trans olefin selectivity [26]. The Mo-catalyzed AROM/CM reaction can be carried out in the presence of vinylsilanes the derived optically pure 74 (Scheme 16) may subsequently be subjected to Pd-catalyzed cross-coupling reactions, allowing access to a wider range of optically pure cyclopentanes. 

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. 

The utility of Ru-catalyzed cross-metathesis in multicomponent coupling strategies has also been demonstrated. For instance, one-pot cross-metathesis/allylboration sequences have been reported by Miyaura [170] and by Goldberg and Grubbs [171]. Pinacol allyl boronate 174 was reacted with a series of functionalized olefins, which include symmetrically 1,2-disubstituted olefins as well as hindered olefins and styrenes, in the presence of catalyst 175 to produce intermediate allyl boro-nates (e.g. 176). The latter may then be reacted in situ with aldehydes to produce functionalized homoallylic alcohols with high levels of anti-selectivity (Scheme 8.80). 

The Mo-catalysed cross-metathesis of acrylonitrile (59) [17,18] and allylsilane (60) [19] with alkenes 61 and 62 produced cross-products 63 and 64 with high selectivity. Reaction of 1-octene with 2 equivalents of styrene (65) afforded 66 in 89% yield. Only small amounts of stilbene (68) and 67 as the homoproducts were formed [23]. 

The chiral Mo-alkylidene complex derived from AROM of a cyclic olefin may also participate in an intermolecular cross metathesis reaction. As depicted in Scheme 15, treatment of meso-67a with a solution of 5 mol% 4a and 2 equivalents of styrene leads to the forma-... 

N-Dienv11richIoroacetamide 174 (11 = 0, R=H) was, however, subsequently also subject to tandem RCM/ATRC catalyzed by the Grubbs II catalyst 175 (Fig. 43) [254]. The yield of 177 in this reaction was reported to be 82-91%, showing that catalyst 175 is also effective in such tandem processes. Tandem cross-metathesis/ ATRC reactions of N- a 11 v 11 ri c h I o ro acetamides with styrenes catalyzed by 175 produced rather low yields of trichlorinated lactams [254]. Almost at the same time Schmidt and Pohler reported similar tandem RCM/ATRC sequences of 1,6-dienyl trichloroacetates with 5 mol% of 175 and of 1,7-dienyl trichloroacetates... 

Cross metathesis of chiral allyhc alcohol or amine moieties and styrene to create phenyl analogues of the parent compounds was achieved using (4a). The phenyl group, in conjugation with the parent molecule, lends a stronger extinction coefficient to the molecules, making the species more amenable for analysis by circular dichroism. ... 

A later report describes AROM/CM of norbomyl alkenes and styrene coupling partners to create asymmetrically functionalized cyclopentanes with alkenyl groups that can be further elaborated. High yields (>98%) of trans (>98) cross metathesis products (predominantly the desired ring-opened, A-B metathesis product) can be achieved using (97a) (equation 22). 

Substituted vinylphosphonates (195) and allylphosphonates (196) with E-olefin stereochemistry have been prepared for the first time via intermolecular olefin cross-metathesis (CM) using ruthenium alkylidene complex (197) in good yield. A variety of terminal olefins, styrenes and geminally substituted olefins has been successfully employed in these reactions (Scheme 49). ... 

On the other hand, our recent study on the highly efficient cross-metathesis of vinyltrialkoxy-and vinyltrisiloxy-silanes with various olefins, for example, with styrene [12] allyl eth [13] and esters [14] as well as octavinylsilsesquioxane [IS] with several olefins have opened a new opportunity for the use of alkene-cross-metathesis in the synthesis of unsaturated organosilicon compounds (see also Refs. [5] and [6]). In this p r new examples of the two reactions involving hetero(N,S,B)organic olefins have been overviewed. 

Cross-metathesis. Functionalization of terminal alkenes by the metathetic method using catalyst 1 has been well established. The reaction between styrene and vinylsilanes gives (o-silylstyrenes, between allylarenes and acrylonitrile leads to 4-aryl-2-butenonitriles. Alternatively, homo-metathesis of two allylarene molecules to give 1,4-diary 1-2-butene is first carried out and the cross-metathesis follows. Also of interest is the homo-metathesis of monosubstituted allenes to symmetrical allenes. ... 

The forward reaction (1) is an example of cross-metathesis between two different olefins and provides a route to styrene. The reverse of (1) is a self-metathesis reaction such reactions may be either productive as in (4), or non-productive (also called degenerate) as in (5). 

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