Second generation metathesis

Origins of Enhanced Reactivity of Second-Generation Metathesis Catalysts 244... 

The mechanistic investigations presented in this section have stimulated research directed to the development of advanced ruthenium precatalysts for olefin metathesis. It was pointed out by Grubbs et al. that the utility of a catalyst is determined by the ratio of catalysis to the rate of decomposition [31]. The decomposition of ruthenium methylidene complexes, which attribute to approximately 95% of the turnover, proceeds monomolecularly, which explains the commonly observed problem that slowly reacting substrates require high catalyst loadings [31]. This problem has been addressed by the development of a novel class of ruthenium precatalysts, the so-called second-generation catalysts. 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

The metathesis of ene-ynamides has been investigated by Mori et al. and Hsung et al. [80]. Second-generation ruthenium catalysts and elevated temperatures were required to obtain preparatively useful yields. Witulski et al. published a highly regioselective cyclotrimerization of 1,6-diynes such as 98 and terminal alkynes using the first-generation ruthenium metathesis catalyst 9... 

Few reports describe the cross metathesis of allyl halides [88]. First-generation catalyst 9 does not seem to be sufficiently reactive to promote this reaction in preparatively useful yields and acceptable catalyst loadings, but second-generation catalyst 56d gives good results for allyl chloride. Cross-metathesis... 

Olefin metathesis of a conjugated diene has recently been exploited by Hiemstra et al. for the synthesis of bicyclic analogs of 116. Second-generation... 

The results obtained with the various metathesis substrates depicted in Scheme 44 demonstrate the lack of a stereopredictive model for the RCM-based formation of macrocycles, not only by the strong influence that may be exhibited by remote substituents, but also by the fact that the use of more reactive second-generation catalysts may be unfavorable for the stereochemical outcome of the reaction. Dienes 212a-f illustrate the influence of the substitution pattern. All reactions were performed with Grubbs first-generation catalyst A... 

In the course of studying a large nnmber of examples where the side chains of the imidazol- and imidazolidin-2-ylidene were altered, several research groups found that NHCs bearing exclnsively alkyl side chains did not provide catalysts with better characteristics when compared to SIMes- and DVIes-derived systems 14 and 15. While Herrmann and co-workers showed that an unsaturated NHC bearing cyclohexyl wing tips conld be incorporated into a second-generation catalyst that was active in metathesis [20-23], more recent studies showed that similar complexes were either very difficult to prepare or were unstable and showed dramatically decreased catalytic properties [24-26] (complexes 17-19, Fig. 3.4). 

In second generation metathesis initiators the NHC ligand is rotating more or less freely, depending on the nature of the active carbene, configuration of ancillary ligands and the steric bulk of the NHC substituents. 

For the last 2 decades ruthenium carbene complexes (Grubbs catalyst first generation 109 or second generation 110, Fig. 5.1) have been largely employed and studied in metathesis type reactions (see Chapter 3) [31]. However, in recent years, the benefits of NHC-Ru complexes as catalysts (or pre-catalysts) have expanded to the area of non-metathetical transformations such as cycloisomerisation. 

Olefin metathesis is one of the most important reaction in organic synthesis [44], Complexes of Ru are extremely useful for this transformation, especially so-called Grubbs catalysts. The introduction of NHCs in Ru metathesis catalysts a decade ago ( second generation Grubbs catalysts) resulted in enhanced activity and lifetime, hence overall improved catalytic performance [45, 46]. However, compared to the archetypal phosphine-based Ru metathesis catalyst 24 (Fig. 13.3), Ru-NHC complexes such as 25 display specific reactivity patterns and as a consequence, are prone to additional decomposition pathways as well as non NHC-specific pathways [47]. 

Ruthenium-Based Second Generation Olefin Metathesis Catalysts and Their Application... 

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