Ring ruthenium catalysed

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 . 

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). 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

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...

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. 

The sertraline precursor is a chiral alcohol with the stereogenic centre adjacent to an aromatic ring. An obvious approach is to make the hydroxyl group by asymmetric reduction of the corresponding ketone. CBS reduction is a possibility, as is a ruthenium-catalysed hydrogenation using the ligand TsDPEN (p. 1115 of the textbook). 

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]. 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

The ruthenium-catalysed arylation, by aryl halides, of benzylic amines carrying a pyridine coordinating group is thought to involve a concerted metallation-deprotonation pathway to give intermediates such as (96), followed by oxidative addition of the aryl halide to ruthenium and then reductive elimination. The reaction can be successM with aryl chlorides, as well as bromides and iodides, but here there are mechanistic differences. The ability of ruthenium to activate remote ring positions to electrophilic substitution has been referred to earlier, see Ref. 97. The reaction of ruthenium-coordinated 2-pyridyl arenes (51) with secondary alkyl halides has been shown to result in the formation of metfl-alkylated products. ... 

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). " ... 

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. 

Blechert S, Stapper C. Enantioselective synthesis of (—)-ana-ferine dihydrochloride by a ruthenium-catalysed tandem ring rearrangement metathesis. Eur. J. Org. Chem. 2002 16 2855-2858. 

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... 

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