Ruthenium-catalysed reactions metathesis

The ruthenium catalysed olefin metathesis reaction is one of the most important catalytic reactions [77-79] and one that is distinctly underdeveloped for asymmetric applications [80]. Only a few concepts have been brought forward [80,81], of which the combination of a NHC ligand with a 1,1-binaphlhyl scaffold carrying a hydroxyl anchor group is the most promising to date. 

Kolb and Meier [43] prepared a malonate derivative of methyl 10-undecenoate, which was polymerised further with 1,6-hexanediol using titanium (IV) isopropoxide as a catalyst. This polymalonate, bearing a C9 aliphatic side chain with terminal double bonds, was then subjected to grafting by ruthenium-catalysed cross-metathesis reactions with acrylates or thiol-ene addition reactions. This functionalisation enabled a subsequent Passerini multi-component reaction [44] using the pendant carboxylic-acid moiety of the modified polymers that resulted from the thiol-ene addition of 3-mercaptopropionic acid into the initial double bonds of the polymer. 

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 . 

Such cases are not uncommon, but full quantitative treatments are rare, since often relatively large amounts of Y must be added to obtain measurable effects. Complications may then arise from the effects of the added Y on the nature of the medium (see Chapters 2 and 3). These are particularly notable when Y and I are charged, as is often the case. Under those circumstances, maintenance of the constant ionic strength of the medium with a known non-participating ionic species is essential. The classic case of common ion depression in solvolysis of benzhydryl chloride is dealt with in Chapter 2. A more recent example of this kind of treatment with neutral reactants occurs in the elucidation of the mechanism of olefin metathesis [20], catalysed by the ruthenium methylidene 9, Scheme 9.6. With ca. 5% of 9, disappearance of diene 10 was clearly not first order. However, reactions run in the presence of large excesses of phosphine 11 were much slower and showed first-order kinetics. The plot of kQ K against 1/ [ 11 ] was linear, consistent with dissociation of 9 to yield an active catalytic species prior to engagement with the diene, with k t [11] 3 > fc2[diene]. Because first-order kinetics were observed under these conditions, determination of order with respect to the catalytic species (as well as the diene) was simplified, and an outline for the mechanism could be constructed (see also Chapter 12 for more detailed consideration of catalysed olefin metathesis). 

Until recently, intermolecular enyne metathesis received scant attention. Competing CM homodimerisation of the alkene, alkyne metathesis and polymerisation were issues of concern which hampered the development of the enyne CM reaction. The first report of a selective ruthenium-catalysed enyne CM reaction came from our laboratories [106]. Reaction of various terminal alkynes 61 with terminal olefins 62 gave 1,3-substituted diene products 63 in good-to-excellent yields (Scheme 18). It is interesting that in these and all enyne CM reactions subsequently reported, terminal alkynes are more reactive than internal analogues, and 1,2-substituted diene products are never formed thus, in terms of reactivity and selectivity enyne CM is the antithesis of enyne RCM. The mechanism of enyne CM is not well understood. It would appear that initial attack is at the alkyne however, one report has demonstrated initial attack at the alkene (substrate-dependent) is also possible, see Ref. [107]. 

On the other hand, several groups have also recently developed asymmetric domino reactions through relay catalysis with combinations of organocatalysts with ruthenium catalysts. For example. You et al. demonstrated in 2009 that ruthenium catalyst could be compatible with Bronsted acid catalyst. They reported a practical and economical synthesis of chiral tetrahydropyrano[3,4-b]indols and tetrahydro-p-carbolines by the combination of ruthenium-catalysed olefin cross-metathesis and a chiral phosphoric acid-catalysed Friedel-Crafts alleviation reaction, as shown in Scheme 7.41. This domino reaction allowed the use of readily available materials to highly enantioselectively construct synthetically valuable polycyclic indole frameworks in enantioselectivity of up to 94% ee. 

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]. 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

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. 

Enyne intramolecular metathesis reactions, of the type shown in equation 61, can be very useful in organic synthesis. A number of such reactions, catalysed by tungsten or chromium carbene complexes, have been reported634,635,737 - 740. The ruthenium carbene catalysts 18-20 (Table 2) are likely to be increasingly used for this purpose because of their stability, ease of handling and good yields, as in the synthesis of various 5-, 6- and 7-membered heterocycles, e.g. equation 67741. 

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