Grubbs metathesis catalysts

There are essentially three different types of transition metal carbene complexes featuring three different types of carbene ligands. They have all been named after their first discoverers Fischer carbenes [27-29], Schrock carbenes [30,31] and WanzUck-Arduengo carbenes (see Figure 1.1). The latter, also known as N-heterocycUc carbenes (NHC), should actually be named after three people Ofele [2] and Wanzlick [3], who independently synthesised their first transition metal complexes in 1968, and Arduengo [1] who reported the first free and stable NHC in 1991. Fischer carbene complexes have an electrophilic carbene carbon atom [32] that can be attacked by a Lewis base. The Schrock carbene complex has a reversed reactivity. The Schrock carbene complex is usually employed in olefin metathesis (Grubbs catalyst) or as an alternative to phosphorus ylides in the Wittig reaction [33]. 

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. 

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]. 

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]. 

Olefin-metathesis is a useful tool for the formation of unsaturated C-C bonds in organic synthesis.186 The most widely used catalysts for olefin metathesis include alkoxyl imido molybdenum complex (Schrock catalyst)187 and benzylidene ruthenium complex (Grubbs catalyst).188 The former is air- and moisture-sensitive and has some other drawbacks such as intolerance to many functional groups and impurities the latter has increased tolerance to water and many reactions have been used in aqueous solution without any loss of catalytic efficiency. 

Figure 5.2 The use of hollow PDMS thimbles to achieve site separation ofGrubbs catalyst and an osmium dihydroxylation catalyst [34], The solution of the Grubbs catalyst was placed on the interior of the PDMS thimble in which a metathesis reaction was then performed. After...

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. 

Although the metathesis of ene-ynes is a valuable method for the preparation of 1,3-butadienes, and may be used for Diels-Alder reactions, a problem arises from the need to employ either a high temperature or a Lewis add to accelerate the cycloaddition, which is usually not feasible with the Grubbs catalyst Therefore, the combination of metathesis and cycloaddition is usually performed in sequential fashion (as just shown, and highlighted earlier) [264]. However, Laschat and coworkers [265] have shown the Lewis acid BC13 to be compatible with the Grubbs I catalyst (6/3-13). Reaction of 6/3-92 and ethyl acrylate using a mixture of 2.5 equiv. of the Lewis acid and 10 mol% of 6/3-13 led to 6/3-93 in 60% yield (Scheme 6/3.27). 

Scheme 8.2. Batch-wise recycling of Grubbs catalyst for ring closing metathesis...

Representatives of the bridged sulfone system 70 have been subjected to ruthenium catalysed ring-closing metathesis reactions (Grubbs catalyst) and shown to afford, in low yields, a few selected cyclic dimers and trimers, of all the possibilities available. The diastereoselectivities observed were rationalised in terms of kinetic control involved with internal ruthenium/sulfonyl oxygen coordination . 

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>. 

The tetrahydro- and perhydropyrrolo[l,2- ]isothiazoles 367 and 368 were synthesized as sulfone derivatives from an olefin metathesis of the diene 366 with the first-generation Grubbs catalyst followed by hydrogenation under palladium on charcoal (Scheme 54) <2003T7047>. 

Recently Cavaleiro et al. described an easy synthetic approach to glycoporphyrins from zinc(n) protoporphyrin-IX dimethyl ester 4 and O-allyl carbohydrate acetonides 5A-E (D-ribose (A), D-galactose (B), D-glucose (C), and two isomeric derivatives (D) and (E) of D-fructose) by cross-metathesis (Scheme 2).12 Two equivalents of each carbohydrate and the Grubbs catalyst were used, giving the carbohydrate derivatives 6 in a range of 74% to 93% yields. 

Ruthenium Carbene-Based Olefin Metathesis Initiators Catalyst Decomposition and Longevity M. Ulman, R.H. Grubbs,/. Org.Chem. 1999, 64, 7202— 7207. 

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