Second-generation ruthenium catalyst

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... 

In recent years, a wealth of information has accumulated on RCM reactions leading to 5-, 6-, and 7-membered carbocycles and heterocycles, so that it is impossible to refer to all the new, natural product-directed work. Therefore, we will concentrate here on a few selected examples that can illustrate (1) the progress made by the advent of the second-generation ruthenium catalysts C-E, (2) the use of RCM in concert with other innovative methodology, and (3) the use of RCM in total syntheses of newly discovered natural products which, due to an outstanding biological profile, have attracted specific interest by the synthetic community. 

The CM reaction between 2-methyl-2-butene (a gera-disubstituted olefin that served in this case also as solvent) and the allylated compound 300, possessing the bicyclo[3.3.1]nonane core of the potential Alzheimer therapeutic garsubellin A (302) [137], underlines the increased activity of the second-generation ruthenium catalysts (Scheme 58). In the presence of 10 mol% of NHC catalyst C, the prenylated compound 301 was formed after only 2 h in 88% yield. 

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. 

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. 

Two tandem alkene metathesis-oxidation procedures using Grubb s second-generation ruthenium catalyst resulted in unique functional group transformations. Use of sodium periodate and cerium(III) chloride, in acetonitrile-water, furnished cis-diols. Oxidation with Oxone, in the presence of sodium hydrogencarbonate, yielded a-hydroxy ketones.296 Secondary alcohols are oxidized to ketones by a hydrogen... 

Second generation ruthenium catalysts N-heterocyclic carbene ligands... 

Scheme 7.11 CO-promoted decomposition pathways of second-generation ruthenium catalysts. Energies (in kcalmoh ) were computed with BP86/SDD-SVP with CPM solvation model in CEIjClj [56].

Mecking et al. [16] reported the preparation of PNBE, PCOD, and PCOE with particle size of 20-30 nm (diameter), based on the use of two aqueous microemulsions. The first one was composed of the monomer, while the second one contained an initiator solution. Grubbs first-generation ruthenium catalyst 6 was used to prepare PNBE, while the more reactive Grubbs second-generation ruthenium catalyst 7 (Scheme 2.1) was necessary to polymerize the less strained cyclo-olefins. With an SDS/pentanol mixture, a stable latex was prepared. 

Other complex symmetrical architectures were obtained using bis-dendritic CTAs [130]. A symmetrical olefin was functionalized, with third-generation Fr chet-type polyfbenzyl ether) dendrons serving as the CTA. Polymerization of COE with the Grubbs second-generation ruthenium catalyst in the presence of this CTA and subsequent hydrogenation with /j-toluenesulfonylhydrazide in o-xylene resulted in bis-dendritic PE (Figure 3.14). 

Scheme 11.5 Grafting of isocyanate-telchelic poly(1,3-di(1-mesityl)-4- [(bicyclo[2.2.1]hept-2-ene-5-ylcarbonyl)oxy]methylF4,5-dihydro-1H-imidazol-3-ium tetrafluoroborate) on silica and generation of the immobilized Grubbs second-generation ruthenium catalyst.

Scheme 11.12 Synthesis of a monolith-supported Grubbs second-generation ruthenium catalyst immobilized via the NHC ligand.

Another important demonstration of indirect activation by irradiation was reported by Frechet et al. [49]. In this approach, the Grubbs second-generation ruthenium catalyst (5wt% solution in toluene) was encapsulated in carbon nanotubes (CNTs) and dispersed in neat DCPD for weeks without any noticeable increase in viscosity. IR laser irradiation resulted in the rupture of the capsules and concomitant polymerization of DCPD, leading to intense gelling within minutes. 

The Grubbs second-generation ruthenium catalyst could be inhibited only by the addition of 20 equiv of MIM [59]. Interestingly, the acid-activated 92 and 94 catalysts were more efficient than their precursors (Grubbs first- and second-generation ruthenium catalysts). For example, ROMP of e vo-ONBE dibutylester... 

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