Grubbs alkene metathesis catalysts

The direct ruthenium catalysed allylation with allylic alcohol derivatives of various aromatic compounds and heterocycles such as furans and thiophenes was performed by Nishibayashi with cationic thiolate-bridged diruthenium(III, II) catalysts. The reaction is consistent with an electrophilic aromatic substitution by the electrophilically activated allyl moiety [68]. Allylation also takes place with the alkene metathesis Grubbs catalyst [69]. More importantly using (phosphine-sulfonate)ruthenium(II) catalyst Bmneau et al. have recently shown that allyl alcohols are activated generating an allyl-ruthenium(IV) intermediate leading to C3-allylation of indole with high regioselectivity in favour of the branched allyl derivative [(Eq. 84)] [167]. 

Ru-catalysed enyne metathesis offers a short approach to chiral derivatives of 3-vinyl-5,6-dihydro-2//-pyrans. Some epimerisation can occur at the pyranyl C atom at elevated temperatures (Scheme 3) <02T5627>. The bispropargyloxynorbomene derivative 6 undergoes a cascade of metathesis reactions in the presence of alkenes and Grubbs catalyst incorporating an enyne-RCM that leads to fused cyclic dienes. A dienophile can be added to the reaction mixture, resulting in Diels-Alder reactions and the formation of functionalised polycyclic products <02TL1561>. 

The mechanism for olefin metathesis is complex, and involves metal-carbene intermediates— intermediates that contain a metal-carbon double bond. The mechanism is drawn for the reaction of a terminal alkene (RCH=CH2) with Grubbs catalyst, abbreviated as Ru=CHPh, to form RCH = CHR and CH2 = CH2. To begin metathesis, Grubbs catalyst reacts with the alkene substrate to form two new metal-carbenes A and B by a two-step process addition of Ru=CHPh to the alkene to yield two different metallocyclobutanes (Step [1]), followed by elimination to form A and B (Steps [2a] and [2b]). The alkene by-products formed in this process (RCH=CHPh and PhCH=CH2) are present in only a small amount since Grubbs reagent is used catalytically. 

General aspects and new metathesis catalysts. For alkene metathesis Grubbs I (1) and Grubbs II (2, 3) complexes, and the Grubbs-Hoveyda catalyst (4A) and Grela catalyst (4B) remain the workhorses. 

The catalysts that have played a dominant role in the development of this area of chemistry are those designed by Schrock (e.g. catalysts 27.1 and 27.2) and Grubbs (catalysts 27.3 and 27.4). Catalyst 27.3 is the traditional Grubbs catalyst , and related complexes are also used. The more recently developed second-generation catalyst 27.4 exhibits higher catalytic activities in alkene metathesis reactions. Catalysts 27.1, 27.3 and 27.4 are commercially available. 

Initial reports of cross-metathesis reactions using well-defined catalysts were limited to simple isolated examples the metathesis of ethyl or methyl oleate with dec-5-ene catalysed by tungsten alkylidenes [13,14] and the cross-metathesis of unsaturated ethers catalysed by a chromium carbene complex [15]. With the discovery of the well-defined molybdenum and ruthenium alkylidene catalysts 3 and 4,by Schrock [16] and Grubbs [17],respectively, the development of alkene metathesis as a tool for organic synthesis began in earnest. 

Other closely related ruthenium-allenylidene were made and evaluated in alkene metathesis [32]. Werner et al. [49] also produced allenylidene complexes of analogous structure to that of the Grubbs catalyst, but containing hemilabile phosphine such as complex X (Scheme 8.9). However, the Ru—O bond may be too stable to initiate the rearrangement into indenylidene, the coordination of alkene and to become a catalyst. 

Alkene metathesis (e.g. 1+2 —> 3) has been known at least since the 1950 s. Until Robert Grubbs of Caltech developed stable and versatile Ru catalysts for this transformation, however, this reaction was little used. 

A detailed study showed that the alkyne-alkene metathesis was proceeding cleanly, but that the product 10 was then decomposed by the Ru catalyst. Use of the less reactive first generation Grubbs catalyst 9 gave clean conversion of 8 to 10. 

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... 

Starting from simple precursors via stereodefined alkenic esters, and ringclosing metathesis using Grubbs catalyst produced p,y-unsaturated lactones, which could be converted into 2,6-dideoxyhexopyranoses.162... 

It is also possible to study the self-assembly of individual molecules as well as networks such as 15.3. The V shaped zinc(II) bis (porphyrin) shown in Figure 15.20a self assembles into decaporphyrin pentagonic and dodecaporphyrin hexagonic assemblies. The assemblies can be fixed by alkene metathesis using Grubbs catalyst. This process represents self-assembly followed by covalent modification as described in Section 10.3.2. The assemblies can be directly imaged by high resolution STM (HRSTM)... 

Facile, regioselective ring opening-cross-metathesis reactions between unsymmet-rical norbornene derivatives and electron-rich alkenes in the presence of the second-generation Grubbs catalyst have been reported to generate highly substituted furans and pyrroles.114... 

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