Ruthenium Catalysed 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 . 

Blechert and co-workers have also reported the application of cross-metathesis to the synthesis of jasmonic acid derivatives containing modified alkene side chains [28]. Molybdenum or ruthenium catalysed cross-metathesis of acetal 20 with various alkenes gave the desired cross-metathesis products in high yields (Eq. 21) (Table 2). 

Ruthenium-catalysed Ring-Opening Metathesis Polymerization (ROMP) 29 526 529 (Equation 10) and Pd(tppms)3-catalysed synthesis of water soluble poly-(p-phenylene) derivatives (Equation ll).530 The latter is a special example of a Suzuki coupling (see earlier). 

This chapter deals with applying ruthenium catalysed olefin metathesis to the synthesis of piperidine and pyrrolidine containing compounds. 

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]. 

Seven-membered lactones can also be prepared in good yields by ruthenium-catalysed cyclocarbonylation of alkenyl alcohols (e.g. 119 from 118) [01TL5459] or by ring closing metathesis using Grubbs imidazolidine catalyst (e.g. 121 from 120, n=2) [02H85]. 

Scheme 7.1 Mechanism in ruthenium-catalysed ring-closing 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. 

An asymmetric route to the fused azepine derivatives 44 has been reported by Pedrosa et al. <05EJO2449>. The power of ruthenium-catalysed ring closing metathesis is further demonstrated in this synthesis, involving conversion of 43 to 44 (e.g. with R = H, R = CH3 82% yield, 92% de). Compounds of type 44 could then be readily converted into the reduced azepin-3-ol derivatives 47 via 45 and 46. 

A similar approach was later employed to prepare rotaxanes by clipping (via ruthenium-catalysed olefin metathesis) the acyclic hydrogen bonding... 

It is used in ruthenium catalysed ring closure metathesis (RCM) and olefin metathesis [Kulkami Diver J.4 r Chem Soc 126 8110 2004, Schmidt Hngew Chem. Int Ed 42 4996 2003, Scholl et al. Org Lett 1 953 1999], and generate imsaturated sultones (e.g. 2,7-3/7-dihydro-[l,2]oxathiepine-2,2-dioxide) from olefinic sulfonates (e g. but-3-enyl allylsulfonate) via ring closure metathesis [Le Flohic et al. Tetrahedron 62 9017 2006]. 

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. 

Nelson DJ, Manzini S, Urbina-Bianco CA, Nolan SP. Key processes in ruthenium-catalysed olefin metathesis. Chem Commun. 2014 50(72) 10355—10375. 

Samojlowicz C, Bieniek M, Pazio A, et al. The Doping effect of fluorinated aromatic solvents on the rate of ruthenium-catalysed olefin metathesis. Chem EurJ. 2011 17(46) 12981-12993. 

Vidavsky Y, Anaby A, Lemcoff NG. Chelating alkyUdene ligands as pacifiers for ruthenium catalysed olefin metathesis. Dalton Trans. 2012 41 32-43. 

A two-step stereoselective strategy for converting glycine-derived aminoesters into unnatural cyclic amino acids has been reported. The process involves a palladium-catalysed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalysed ring-closing metathesis (Scheme 175). " ... 

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. 

A highly efficient synthetic route to neurotoxic spirocyclic alkaloids such as perhydrohistrionicotoxin has been described in which the key steps are a selenium-mediated [2,3]-sigmatropic rearrangement and a ruthenium-catalysed ring-closing metathesis. 

---