Alkynes cross metathesis with alkenes

With the discovery by Grubbs of ruthenium carbene complexes such as Cl2(PCy3)2Ru=CHR, which mediate olefin metathesis under mild reaction conditions and which are compatible with a broad range of functional groups [111], the application of olefin metathesis to solid-phase synthesis became a realistic approach for the preparation of alkenes. Both ring-closing metathesis and cross-metathesis of alkenes and alkynes bound to insoluble supports have been realized (Figure 5.12). 

Both catalysts 1 and 2 are effective in promoting cross-metathesis leading to various conjugated dienes from alkenes and alkynes. Chiral 2-(a-acetoxybenzyl)-1,3-butadiene is obtained from (/f)-3-acetoxy-3-phenylpropyne via cross-metathesis with ethylene. - Furthermore, the reaction of 1,6-diynes with alkenes is even more intriguing ... 

The use of alkyne cross metathesis for the synthesis of unsymmetrical alkynes has potential utility in synthesis, although it has been studied less intensively than alkene cross metathesis. Mori published some of the first examples of alkyne cross metathesis to generate unsymmetrical alkynes. One example of this reaction conducted with the Montreux-type catalyst is shown in Equation 21.37. The selectivity for the cross-metathesis product was achieved by the use of an excess of the diphenylacetylene. A second example was conducted with the catalyst generated from Cummins trisamido complex. As shown in Equation 21.38, this cross metathesis was conducted in acceptable yields... 

These developments were extended to multistep reactions on the solid support, for example, via immobilization of the alkene or the alkyne component as an ester. The immobilized alkyne 34 created the possibility for a cross metathesis with a soluble olefin however, as previously noted, undesired CM products generated from soluble alkenes can easily be removed by filtration and washing. After ene-yne cross metathesis to 35, the resin... 

The reactivity and stereoselectivity of metathesis are not well understood at present. Conjugated carbene complexes (—CR=CH—CR=M) react faster with alkynes than with alkenes and conversely for nonconjugated types.Using [W(CO)2(AsPh3)2Cl2], degenerate metathesis of 3,3-dimethylbut-l-ene is much faster than productive metathesis. In cross-metathesis with norbomadiene the main chain carrier seems to be W=CHC(CH3)3. Stereoselectivity is generally... 

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. 

Blechert reported a skillful method of cross-enyne metathesis. Solid-supported alkyne 139 is reacted with alkene in the presence of Ic to give 140. For cleavage of 1,3-diene from solid-supported product 140 having an allyl acetate moiety, palladium-catalyzed allylic substitution is used. Thus, 140 is treated with Pd(PPh3)4 in the presence of methyl malonate to afford three-component coupling product 141 in good yield ... 

The intermolecular enyne cross metathesis, and consecutive RCM, between a terminal alkyne and 1,5-hexadiene produces cyclohexadienes, by cascade CM-RCM reaction, and trienes, formed during the sole CM step. Studies of various parameters of the reaction conditions did not show any improvement of the ratio of desired cyclohexadiene product [25] (Scheme 12). The reaction with cyclopentene instead of hexadiene as the alkene leads to 2-substituted-l,3-cycloheptadienes [26]. After the first cyclopentene ROM, the enyne metathesis is favored rather than ROMP by an appropriate balance between cycloalkene ring strain and reactivity of the alkyne. 

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... 

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... 

Olefin metathesis is a reaction that is over fifty years old and has been developed over this time period from a process nm at high temperatures with ill-defined catalysts by unknown mechanisms to a process that can be conducted imder nuld conditions with designed catalysts by mechanisms that occur by established steps. Olefin metathesis, and the related alk3me metathesis, fully cleaves carbon-carbon double and triple bonds and reforms these bonds to generate new alkenes and alkynes. The reaction is often under equilibrium control, but certain classes of reactions can be conducted in a selective fashion that is controlled by relative rates or thermod)mamic preferences. This reaction can open strained rings to form polymers or small dienes. It can close small rings and macrocycles by a reaction that is driven by the expulsion of ethylene that makes the reaction favored entropically or by running in an open system under non-equilibrium conditions. It can also be run as a "cross metathesis" to form imsymmetrical alkenes when the steric or electronic properties of the two alkenes properly match. 

Cross-enyne metathesis has also been applied to solid-phase synthesis by immobilizing either the alkyne or the alkene (498,499). By combination with a Diels-Alder reaction, this process has been used to create a combinatorial library of various six-membered ring structures (500). Within this theme, intermolecular enyne metathesis is the integral synthetic method used to produce novel amino acid derivatives (501, 502). To this end, the aromatic ring of highly substituted phenylalanines was synthesized through enyne crossmetathesis and cycloaddition. 

Suzuki-Miyaura cross-coupling polymerization of 1,4-bis((Z)-2-bromovinyl)benzenes with aryl-bis-boronic acids. The interest has been in an alternative approach, where rather than building a PPV with a pre-ordained stereochemistry, a postpolymerization yyn-selective reduction on a poly(phenylene ethynylene) (PPE) is used [125]. This scheme has the advantage that high molecular weight PPEs can be synthesized using either Pd-catalysis or alkyne metathesis. This route could also potentially allow for the access to an additional array of PPVs that are uniquely accessible from PPEs. The transformation of the triple bonds in PPEs and other acetylene building blocks to alkenes has considerable potential. 

Cross-Enyne Metathesis/Diels-Alder MCRs Ruthenium-based complexes are known to catalyze the metathesis between alkynes and alkenes to afford 1,3-dienes. Fnstero, del Pozo et al. further exploited this cross-enyne metathesis (CEYM) by trapping the 1,3-diene with a dieno-phile via an intermolecnlar Diels-Alder reaction [198]. Thns, the Ru-catalyzed MCR between alkynes 220-221 and 1,7-octadiene as an in situ sonrce of ethylene by RCM generates a 1,3-diene that can snbseqnently nndergo a Diels-Alder reaction with a wide variety of dienophiles 222... 

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