Alkene metathesis reaction applications

Some general reviews relating to the chemistry of Ru/Os-r hydrocarbon complexes appear in the literature the reactivity of Ru-H bonds with alkenes and alkynes/ aspects of ruthenium/osmium vinylidene/allenylidene/cumul-enylidene complexes,equilibria of M-R/M=CR2/M=CR complexes, the organometallic chemistry of metal porphyrin complexes, and the reactions of [Os(P Pr3)2(CO)HGl], ruthenium pyrazoly I borate complexes,and metallabenzynes. Other reviews relate more to applications of some of the complexes outlined in this chapter. See, for example, metal vinylidenes in catalysis,the development of Grubbs-type alkene metathesis catalysts, applications of ruthenium/osmium carbene complexes in metathesis polymerization, and the role of Ru /V-hetero-cyclic carbene complexes in metathesis polymerization. ... 

Metallacycles, cyclic alkyls L M(CH2) , are associated with two reversible reactions. In Eq. 3.22, an n = 3 metallacyclobutane rearranges to an alkene and a carbene, a key step in the important alkene metathesis reaction, and in Eq. 3.23, an n = 4 metallacyclopentane rearranges to give two alkenes. Metallacycle applications are discussed in Sections 6.8 and 12.1. 

We have witnessed the remarkable advance of selective alkene metathesis reactions over the last a few years. Many synthetic chemists have utilized this reactiOTi as a very practical, versatile, and selective synthetic tool to prepare complex molecules including natural products. Selective alkene metathesis has helped to elevate the art and science of natural product total synthesis to its present high level. However, many critical discoveries in catalytic alkene metathesis, particularly the development of more effective catalysts that are easily obtained and able to provide excellent selectivities, remain to be made. It has been delightful to review this field and highlight some of the most significant and exciting examples of recent applications of selective alkene metathesis in the total synthesis of complex natural... 

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. 

Applications of the cross-metathesis reaction in more diverse areas of organic chemistry are beginning to appear in the literature. For example, the use of alkene metathesis in solution-phase combinatorial synthesis was recently reported by Boger and co-workers [45]. They assembled a chemical library of 600 compounds 27 (including cisttrans isomers) in which the final reaction was the metathesis of a mixture of 24 oo-alkene carboxamides 26 (prepared from six ami-nodiacetamides, with differing amide groups, each functionalised with four to-alkene carboxylic acids) (Eq.27). 

The cross-metathesis reaction has evolved extensively during the past few years, but there is still a considerable amount of work to be done before the full potential of this reaction is realised. The development of new metathesis catalysts, greater understanding and control of selectivity, and more extensive applications in synthesis that will surely follow in the near future, make this a particularly exciting time in the evolution of the alkene cross-metathesis reaction. 

Effectively, this is another example of the addition of a functional aromatic compound to an alkene, as the Murai reaction, but the mechanism is different. Alkyl substituted pyridine derivatives are interesting molecules for pharmaceutical applications. The a-bond metathesis reaction is typical of early transition metal complexes as we have learnt in Chapter 2. 

Much of the chemistry of vinylidene complexes has been developed with catalytic applications in mind, as detailed later in this volume. Early examples had low activity for alkene metathesis, although complexes containing imidazolylidene ligands showed improved efficiencies [35]. However, in many cases, reactions of the vinylidene ligand have resulted in transformation to other carbon-based ligands which have not been released from the metal fragment. 

Moreover, Fiirstner shotved that tvhereas complex VIII was inactive for RCM reaction, its PCy3 analog IX was, in contrast, very active in a variety of RCM reactions. The latter is now commercially available and currently used in alkene metathesis (see Section 8.3 for further applications). 

Actually, applications of indenylidene-ruthenium complexes for alkene metathesis were reported before, at a time when the action mode of their ruthenium allenylidene precursors was not known. These complexes catalyzed a variety of RCM reactions of dienes and enynes [31, 32, 47] (see Section 8.2.2). 

Metathesis of alkynes is a much less general reaction and has not yet found the attention that alkene metathesis has received.158-160 Nonetheless, a few observations have shown that it has the potential of useful applications emerging as a new synthetic tool.214-216... 

Since many metal fragments are isolobal with CH2, it should be possible to make a range of metallacycloalkanes. Metallacyclobutanes are well known as a class of compounds and serve as key intermediates in catalytic alkene metathesis.1 This reaction has gained great importance in recent years through the work of Grubbs2 and Schrock.3 Alkene metathesis has many applications in organic chemistry,... 

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]. 

The application of alkene [1] - and, more recently, enyne [2] and alkyne - metathesis to the synthesis of natural products has been triggered by the development of powerful catalysts that allow metathesis reactions to be carried out under mild conditions. Scheme 1 outlines two important cases of alkene and alkyne metathesis of particular interest to the synthesis of natural products (together with the general scheme of enyne metathesis, not discussed in this review). The metathesis products can be obtained in high yields, since ethene/2-butyne are formed as volatile products. After the alkene/alkyne metathesis, the substituents (R) of the alkenes/alkynes are located on the same multiple bond. Enyne metathesis can be considered as the more general case of alkene metathesis, because two new double bonds are again formed, albeit now connected by a single bond. 

---