Metathesis catalyst stereoselectivity

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. 

This review article offers an overview of stereo- and regioselective processes, developed in our laboratories, that are carried out in conjunction with various catalytic RCM reactions. As mentioned above, several reaction technologies involve stereoselective functionalization of the RCM products, and others were developed such that subsequent reactions effected by a metathesis catalyst promote the formation of the desired target molecules selectively and efficiently. 

Most of these catalytic systems are able to dimerize either aromatic alkynes, such as phenylacetylene derivatives, or aliphatic alkynes, such as trimethylsilylacetylene, tert-butylacetylene and benzylacetylene. The stereochemistry of the resulting enynes depends strongly on both the alkyne and the catalyst precursor. It is noteworthy that the vinylidene ruthenium complex RuCl(Cp )(PPh3)(=C=CHPh) catalyzes the dimerization of phenylacetylene and methylpropiolate with high stereoselectivity towards the ( )-enyne [65, 66], and that head-to-tail dimerization is scarcely favored with this catalyst. It was also shovm that the metathesis catalyst RuCl2(P-Cy3)2(=CHPh) reacted in refiuxing toluene with phenylacetylene to produce a... 

Despite the remarkable success of olefin metathesis catalysts in organic applications, one major challenge that remains is the diastereomeric control of olefin geometry. Olefin stereoselectivity is an issue in all metathesis reactions. However, prior to the widespread use of CM processes, it was only pertinent to the RGM of large rings (>8 carbons) and in the backbone structure of ROMP-derived polymers. 

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... 

Recently, it was shown that the metathesis catalyst RuCl2(PCy3)2(=CHPh), where Cy is cyclohexyl, reacted in refluxing toluene with phenylacetylene to produce a ruthenium vinylidene species which promoted the regioselective dimerization of phenylacetylene into ( )-1,4-diphenylbutenyne [56]. The addition of 1 Eq acetic acid did not lead to enol esters but to a faster reaction and the stereoselective dimerization of phenylacetylene into the Z dimer. 

Chiral polymers have been applied in many areas of research, including chiral separation of organic molecules, asymmetric induction in organic synthesis, and wave guiding in non-linear optics [ 146,147]. Two distinct classes of polymers represent these optically active materials those with induced chirality based on the catalyst and polymerization mechanism and those produced from chiral monomers. Achiral monomers like propylene have been polymerized stereoselectively using chiral initiators or catalysts yielding isotactic, helical polymers [148-150]. On the other hand, polymerization of chiral monomers such as diepoxides, dimethacrylates, diisocyanides, and vinyl ethers yields chiral polymers by incorporation of chirality into the main chain of the polymer or as a pedant side group [151-155]. A number of chiral metathesis catalysts have been made, and they have proven useful in asymmetric ROM as well as in stereospecific polymerization of norbornene and norbornadiene [ 156-159]. This section of the review will focus on the ADMET polymerization of chiral monomers as a method of chiral polymer synthesis. 

Whereas phosphanes have a conical shape, much of which is decisive in stereoselective catalysis, the A -heterocyclic carbenes (NHCs) exhibit flat core structures. More importantly, phosphanes dissociate from metal centers in common catalysts, whereas the C-coordination of the new ligands is much more stable under catalysis conditions, thus preventing the catalytically active metal from aggregating and precipitating. Theoretical studies (DFT cf. Section 3.1.2) showed that the phosphanes in the Ru metathesis catalyst 24 dissociate much more easily (ca. 27 kcal/mol) from the metal than the carbene in 25 (ca. 21 kcal/mol) the... 

STUDY OF THE ACTIVITY AND STEREOSELECTIVITY OF SOME METATHESIS CATALYSTS WITH ACYCLIC INTERNAL OLEFINS... 

ABSTRACT. Cyclometalated aryloxy(chloro)neopentylidene-tungsten complexes can be synthesized starting from WCl4(OAr)2 (OAr = 2,6-disubstituted phenoxide), but also starting from the neopentylidyne complex W(CCMe3)Cl3(dme) (by reaction with LiOAr). Some of these cyclometalated neopentylidenes are probably among the most active and stereoselective one-component metathesis catalysts. In particular, they are fairly active in the metathesis of an olefinic ester such as ethyl oleate and they have been successfully used in the metathesis of olefinic sulfides. 

The past decade has witnessed extensive modifications of Af-heterocyclic carbene ligands for ruthenium olefin metathesis catalysts. This includes symmetrical and unsymmetrical NHCs, 1,3- and 4,5-substitutions, introduction of heteroatoms into the backbone, NHC ring size variation, and introduction of chirality. Most of these changes were initially targeted to improve stability and activity of the catalyst, while recent approaches are mainly focused on affording well-defined stereoselectivity. However, the activity and stability of the ruthenium-based metathesis catalysts are not solely ruled by the type of neutral NHC ligand the anionic ligands, chelation mode, substrates used, and the reaction conditions naturally also influence catalytic properties. One of the main lessons learned from ruthenium olefin metathesis development is that there is no one catalyst fits all and every type of application must be studied in detail in order to discover the most efficient catalytic complex. 

Sattely ES, Meek SJ, Malcolmson SJ, Schrock RR, Hoveyda AH. Design and stereoselective preparation of a new class of chiral olefin metathesis catalysts and application to enantioselective synthesis of quebrachamine catalyst development inspired by natural product synthesis. J. Am. Chem. Soc. 2009 131 943 953. 

Cyclooctadiene, metathesis of, 135 stereoselectivity, 159, 160 Cyclooctene, metathesis of, catalysts for, 140... 

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