Method 5 Alkene Metathesis

When a mixture of alkenes 1 and 2 or an unsymmetrically substituted alkene 3 is treated with an appropriate transition-metal catalyst, a mixture of products (including fi/Z-isomers) from apparent interchange of alkylidene moieties is obtained by a process called alkene metathesis. With the development of new catalysts in recent years, alkene metathesis has become a useful synthetic method. Special synthetic applications are, for example, ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROM) (see below). 

Fig. 17. Mechanistic studies of alkene metathesis provided methods to increase the rates of reaction. Copper (I) chloride and hydrochloric acid have been used to encourage dissociation of the phosphine ligands...

The formation of carbon-carbon bonds has always been one of the key challenges in synthetic organic chemistry, and particularly methods to obtain optically pure products are of fundamental importance. In DCC, however, with the exception of the powerful alkene metathesis reaction, C-C bond formation has only been explored in a few systems [1,5,6,18-20]. 

This stoichiometric reaction constitutes a new contribution to vinylidene chemistry and a novel method to generate alkenylcarbene ligand from simple propargyl alkyl ethers rather than via activation of cyclopropenes [4] or by stoichiometric activation of butadiene [6[. When linked to a suitable metal-ligand moiety this carbene constitutes an alkene metathesis initiator. 

Distal C-C bond formation can also be used to construct cyclic ethers, but this demands that methods be developed for the enantioselective assembly of complex acyclic ethers. P. Andrew Evans of Indiana University has demonstrated (Angew. Chem. Jnt. Ed. 2004, 43,4788) that Rh-mediated coupling of secondary allylic carbonates such as 7 with secondary alcohols such as 8, both enantiomerically pure, proceeds with clean retention (double inversion) of absolute configuration. Alkene metathesis then delivers the cyclic ether 9 in high diastereomeric and enantiomeric purity. 

More recently, linkers similar to 4, making use of alkene metathesis as the cleavage method, have been developed.37,38 Alkene-type linkers are stable to acidic and basic reaction conditions, and the double bond acts as a handle for the final cleavage event. This is an attractive option because the linker... 

As is evident from the selected examples discussed here, domino metathesis reactions are fast becoming a method of choice for the rapid synthesis of complex ring structures from simple building blocks. The recent advances in catalyst technology and associated widening of the scope of alkene metathesis seems certain to further augment the importance of these relatively unexplored reactions in years to come. 

Ring opening metathesis polymerization, which has been known since the discovery of the alkene metathesis reaction, has been given the acronym ROMP in recent years. In fact, the ROMP reaction was the first observation made in alkene metathesis chemistry, while the discovery of the exchange reaction in equation (1) actually occurred later. Acychc diene metathesis (ADMET) polymerization (equation 3) has only recently been shown to be a viable method for polymer synthesis, and it has been termed ADMET polymerization. ROMP reactions are driven by the release of ring strain from the monomer, while ADMET polymerization is driven by a shift in the equilibrium caused by the removal of one of the reaction products. 

The alkene metathesis reaction between carbon-caibon double bonds is now a well-established synthetic method in industrial operations and in the laboratory. Recently it has been recognized that a closely related, transition metal catalyzed reaction takes place between a carbon-carbon double bond and a carbon-oxygen double bond. lliis latter process, which can be considered as a Wittig analog, shows promise of becoming an important tool of synthesis strategy. ... 

Alkene-alkene metathesis reactions are a valuable method to construct cyclic compounds (see Section 2.10). Alkene-alkyne reactions can also be effective. Explain the formation of the bicyclic product 16. 

According to the nature of alkene metathesis, this general reaction can be divided into different subgroups cross-metathesis (CM), ring-closing metathesis (RCM), ringopening metathesis polymerization (ROMP), and acyclic diene metathesis polymerization (ADMET). " From an industrial perspective, a more cost-effective method for alkene metathesis is to generate the metallo-carbene in situP This reaction has been extensively reviewed. ... 

In Section 24.12, we introduced alkene (olefin) metathesis, i.e. metal-catalysed reactions in which C=C bonds are redistributed. The importance of alkene and alkyne metathesis was recognized by the award of the 2005 Nobel Prize in Chemistry to Yves Chauvin, Robert H. Grubbs and Richard R. Schrock for the development of the metathesis method in organic synthesis . Examples of alkene metathesis are shown in Figure 27.3. The Chauvin mechanism for metal-catalysed alkene metathesis involves a metal alkyli-dene species and a series of [2 + 2]-cycloadditions and cycloreversions (Figure 27.4). Scheme 27.6 shows the mechanism for alkyne metathesis which involves a high oxidation state metal alkylidyne complex, L M=CR. 

Alkene Metathesis. Alkene metathesis is a simple and effective method of the synthesis of useful compounds, which otherwise would require complex synthetic procedures. With the commercial availability of various catalysts of high activity and selectivity, the importance of alkene metathesis keeps up growing (190). Interestingly, although there are many highly active water-soluble metathesis catalysts known (71,72,191) the number of aqueous-organic bipha-sic procedures is relatively small. 

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