Stereoselectivity, alkene metathesis catalyst

Catalytic ring-closing metathesis makes available a wide range of cyclic alkenes, thus rendering a number of stereoselective olefin functionalizations practical. The availability of effective metathesis catalysts has also spawned the development of a variety of methods that prepare specially-outfitted diene substrates that can undergo catalytic ring closure. The new metathesis catalysts have already played a pivotal role in a number of enantioselective total syntheses. 

The stereoselectivity of olefin formation is crucial to the utility of CM. To date, a general metathesis catalyst capable of effecting diastereomeric control over a broad range of substrates has yet to be realized. Of particular interest is the development of a Z-selective catalyst, as Z olefins are a prevalent structural motif within both natural products and pharmaceutical agents.Current examples of Z-selective olefin CM have proved to be substrate dependent. These include the CM of enynes with alkenes, acrylonitrile the CM reaction... 

Recent efforts have achieved Z-selective ruthenium carbene catalysts, providing a catalyst solution to a general problem in stereoselective alkene synthesis Diastereoselectivity in Olefin Metathesis Development of Z-Selective Ru Catalysts Vol 1, Chapter 3 Grubbs, Handbook of Metathesis, 2nd Edition, Volume 2, Chapter 7. As this is a relatively new field, mechanistic studies are... 

Catalysts continue to be developed for particular alkene metathesis applications, such as stereoselective cross metathesis. These precatalysts are tasked with selective metathesis and turnover, but must maintain Z-selectivity throughout the reaction. New ruthenium(II) species featuring a Ru-C bond have been recruited for this purpose. In a short time, reactivity gains and improved initiation rates have been achieved in this new area by manipulation of the X-type ligand. 

Alkene metathesis has significant advantages in natural product synthesis for several reasons. First, alkene moieties broadly exist in numerous natural products, and alkene metathesis allows facile access from the readily available or easily prepared olefins to those that are difficult to access. Second, alkene metathesis reactions either do not produce any by-product or only generate the volatile ethylene. Third, alkenes are relatively stable in the multistep synthesis, and are sufficiently reactive to be used in a wide range of transformations to generate other functionalities under specific reaction conditions. Finally, and most importantly, with the help of effective catalysts, alkene metathesis can provide remarkable selectivities (regio-, chemo-, and stereoselectivity) in the challenging synthetic operations. 

Thus far, chemists have been able to influence the stereoselectivity of macro-cyclic RCM through steric and electronic substrate features or by the choice of a catalyst with appropriate activity, but there still exists a lack of prediction over the stereochemistry of macrocyclic RCM. One of the most important extensions of the original metathesis reaction for the synthesis of stereochemi-cally defined (cyclo)alkenes is alkyne metathesis, followed by selective partial hydrogenation. 

W(NAr)(=CHBuO(OR)2 (R = CMe(CF3)2, 50) are highly active catalysts for the metathesis of internal alkenes (equation 16), and also effect the stereoselective olefmation of hydroxy ketones (equation 17). The reactivity of these catalysts can be tuned by varying the aUcoxide ligands for example, when R = Bn, the complex acts only upon strained cyclic alkenes and is a highly effective ring-opening metathesis polymerization (ROMP) catalyst (see Metathesis Polymerization Processes by Homogeneous Catalysis). 

A major goal in olefin metathesis, as in any alkene synthesis, has been the control of the stereochemistry of the alkene product. The overall stereoselectivity observed in an olefin metathesis reaction can be a function of both kinetic and thermodynamic selectivity. This is because the primary metathesis products, which are produced under kinetic selectivity, can often reenter the metathesis cycle to give thermodynamically controlled stereoselectivity [27]. For many catalysts, including the first- and second-generation Grubbs catalysts, the... 

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