Solution-phase metathesis, synthesis

Applications of the cross-metathesis reaction in more diverse areas of organic chemistry are beginning to appear in the literature. For example, the use of alkene metathesis in solution-phase combinatorial synthesis was recently reported by Boger and co-workers [45]. They assembled a chemical library of 600 compounds 27 (including cisttrans isomers) in which the final reaction was the metathesis of a mixture of 24 oo-alkene carboxamides 26 (prepared from six ami-nodiacetamides, with differing amide groups, each functionalised with four to-alkene carboxylic acids) (Eq.27). 

Synthesis of m-V Semiconductor Nanocrystals by Solution Phase Metathesis... 

Boger, D.L., Chai, W., Ozer, R.S. and Andersson, C.-M., Solution-phase combinatorial synthesis via the olefin metathesis reaction, Bioorg. Med. Chem. Lett., 7 (1997) 463-468. Boger, D.L., Ozer, R.S. and Andersson, C.-M., Generation of targeted Ci-symmetrical compound libraries by solution-phase combinatorial chemistry, Bioorg. Med. Chem. Lett., 7 (1997) 1903-1908. 

The classic ylid-based reactions used in the solution-phase synthesis of olefins have been applied successfully to the solid-phase. Cross-metathesis has been performed with a resin-bound and a dissolved olefin to provide more highly functionalized olefins. 

A similar method has been developed by Seeberger et al. for metathesis reaction with pentene to give octene-substituted monosaccharide derivatives [373]. In previous solution phase experiments three catalysts were screened at different temperatures and in different solvents which suggest that metathesis proceeds best in dichloromethane at 0°C and with (H2lmes)(3-Br-py)2-(Cl)2Ru = CHPh] as the catalyst. AU soUd phase experiments have been performed on Merrifield octenediol linker 731 and have been checked for the cleavage reaction with ethylene as described in Scheme 109 for the synthesis of terminal olefins. 

The functional group tolerance of the ruthenium-based metathesis catalysts has had a tremendous impact on solid-phase organic synthesis. The efficacy of the reaction in solution generally translates directly to solid-phase transformation and its potential has been harnessed in a number of library syntheses, solid-phase syntheses of natural products, or diversity-oriented syntheses. It enables the use of chemically robust alkenes as linkers which can be cleaved by RCM or CM. It, of course, provides new manifolds of diversification in diversity-oriented synthesis as has been elegantly shown in landmark examples by Schreiber and Nelson. Another metathesis application of paramount importance is in peptide chemistry where solid-phase synthesis is omnipresent. The ability to stabilize secondary structures in short peptide motifs and replace pharmacologically unsuitable disulfide bonds or simply restrict the conformation of a peptidic library has already been successfully implemented in a number of important examples. The orthogonality of the metathesis reaction to peptide chemistry provides a really powerful tool in this regard. 

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