Second generation metathesis catalyst

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

Adlhart and Chen [126] reported a QM/MM study of the olefin-metathesis reaction catalyzed by [L2(Cl)2Ru=CHPh] complexes L are phosphane groups in the case of the first-generation catalyst, whereas for the second-generation catalysts an N-heterocyclic carbene ligand replaces one of the phosphanes. A study of first- and second-generation metathesis catalysts... 

Figure 7.14 Comparison of conventional Grubbs second generation metathesis catalyst (left) and Gladysz s fluorous version (right).

Reaction of (72) with aryl A -substituted NHC, yielding second-generation metathesis catalysts, was reported in 1999 by Nolan ef a/ and Grubbs ef a/ Substitution of one phosphine in (72) by IMes afforded [Cl2Ru(IMes)(PCy3)(CHPh)] in excellent yields. Even in the presence of a 10-fold excess of IMes, only one phosphine underwent substitution. Since then, this synthetic route has been extended to a number of car-benes, for instance, SIMes, for which the free carbene has been generated in situ from the methanol-protected NHC (14), IPr, SIPr generated either from the terf-butanol-protected... 

Treatment of Grubbs second-generation metathesis catalyst with carbon monoxide results in a Buchner rearrangement in which the alkylidene inserted into one of the aryl substituents of the NHC (Scheme 3.18)."" It was proposed that CO, being a strong 71-acceptor, decreases the electron density available for back donation and stabilization of the alkylidene ligand. The alkylidene thus becomes more electrophilic, and is attacked by the adjacent aryl ring. 

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... 

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]. 

The main reason for the rapid development of metathesis reactions on a laboratory scale (the reaction itself had been known for quite a long time) has been the development of active and robust second-generation ruthenium catalysts (6/3-14 to 6/3-16), which usually provide better yields than the first-generation Grubbs catalysts (6/3-9 or 6/3-13) (Scheme 6/3.2). This also reflects the huge number of domino processes based on ruthenium-catalyzed metathesis, which is usually followed by a second or even a third metathesis reaction. However, examples also exist where, after a metathesis, a second transition metal-catalyzed transformation or a pericyclic reaction takes place. 

A synthesis of 5//-pyrrolo[l,2-r] imidazole 105 has been developed via a chemoselective addition/dehydration of acetaldehyde on diiodo imidazole 103 giving the vinylic imidazole 104. This compound, treated under the metathesis condition in the presence of the second-generation Grubbs catalyst, gave the final product 105 (Scheme 11) <2003TL1379>. 

Pawlow et al. (3) prepared multifiinctionalized high-trans-content elastomeric polymers using Grubbs second-generation ruthenium catalyst in the metathesis polymerization of cyclooctadiene, cyclopentene, and l,4-bis(trimethoxysilyl)-2-butene. 

The cyanthin diterpenes show physiological activity ranging from cytotoxicity to nerve-growth factor stimulation. Andrew J. Phillips of the University of Colorado recently described (J. Am. Client. Soc. 2005,127,5334) a concise cnantioselective synthesis of cyanthiwigin U 3, based on the metathesis conversion of 1 to 2, using the second generation Grubbs catalyst. 

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