Cross-metathesis on Solid Phase

Figure 13.10 Pioneering examples of cross-metathesis on solid phase.

Selected examples of these and related applications are authoritatively discussed in the chapters by K.C. Nicolaou et al. (epothilone libraries) and S.E. Gibson and S.P. Keen (cross metathesis processes on solid phase) in this monograph. For some further advancements, the reader is referred to the recent literature [45]. 

Geert-Jan Boons et al. also synthesized peptidoglycan fragments such as the disaccharide repeating unit [51] and muramyl peptide derivatives containing Lys and DAP residues [52-55] obtained through cross olefin metathesis [56], The muramyl peptides, such as 48 prepared by solid-phase synthesis on Sieber amide resin (Scheme 14.6), were subjected to biological and structural analyses [50, 57, 58] of... 

A general problem of alkene cross-metathesis is the formation of self-condensation products from the starting alkenes. On the solid phase, dimerization of polymer-bound alkene should be miniinized by the use of excess alkene in solution combined with the effective dilution of the resin-bound alkene by site isolation effects (see Suzuki coupling). Homocoupled products of the solution phase alkene are simply washed way during the resin washes. 

The solid phase polysaccharide synthesis is performed on Metrifield s polystyrene resin functionalized with 4-octenediol linker. This linker is stable during the synthesis cycles but can be cleaved by Gmbbs catalyst (cross-metathesis reaction) resulting in fuUy protected polysaccharide, which can be used for further functionalization or deprotected in its native state. The final purification is achieved by high-performance hquid chromatography, which in some cases also can be used to separate the different stereoisomers of the final products [58]. 

Muscone (40) is a sex pheromone of the musk deer and a chemical component of cosmetics. A 12-member library of racemic muscone analogs was synthesized by Nicolaou et al.," who anployed a cyclorelease method on solid support to form the macrocycle scaffold (Figure 11.17). A phosphonate-functionalized resin loaded on encoded SMART microreactors 36 was coupled to olelinic esters 35 to form the p-ketophosphonates 37. Sorting and cross olefin metathesis of 37 with two alkenols followed by oxidation with Dess-Martin reagent gave aldehydes 38. An intramolecular ketophosphonate-aldehyde condensation (Homer-Emmons-Wadsworth reaction) of 38 caused smooth cyclorelease of macrocyclic enones 39. Parallel solution-phase chemistry completed the sequence. 

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