Polystyrene Resin-Supported Scavengers

Since the discovery of solid phase peptide synthesis in 1963 [4], the venerable polystyrene resin has remained the cornerstone of combinatorial chemistry over the years and continues to be utilized as the primary mode of support for immobilizing reagents and scavengers. This section briefly outlines the latest developments of resin-based scavengers. 

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Application of Polystyrene Resin-Supported Scavengers towards the Synthesis of Natural Products... 

Maleimide is a well-known Michael acceptor, dienophile and dipolarophile and hence is another versatile functional moiety that has found multiple uses in combinatorial chemistry as both a scavenger as well as a template in library synthesis [15]. Barrett [16] and Porco [17] have both reported the synthesis of a polystyrene resin-supported maleimide but did not report its use in the scavenging of nucleophiles. Hall and coworkers have described the synthesis of a supported-maleimide... 

Thus, gel-type polystyrene-sulfonyl-hydrazide resin 20, which originally was developed for carbonyl scavenging applications [30] can also serve as a linker for carbonyl compounds in solid phase synthesis and gives access to support-bound sulfonyl hydrazones 21 (Scheme 8)... 

Phase-switching strategy was applied to the multistep synthesis of isoxazolines 45-47. The approach exploits the boronic acid functionality as a phase-tag which can be easily immobilized on diethanolaminomethyl polystyrene (DEAM-PS) resin and then released by treatment with wet THF. Each reaction step was carried out in solution and the products were purified by addition of the scavenging resin, followed by filtration, washing of the supported material, hydrolytic release and evaporation. Finally, the boronic acid could be used to introduce additional substituents on the molecule. For example, 46 was converted into the biaryl-containing isoxazoline 47 by a Suzuki cross-coupling reaction <07JCO193>. 

Recently, various scavenger resin approaches have appeared in the literature. For the synthesis of 4000 ureas (400 pools of 10-compound mixtures) [47], a solid-supported amino nucleophile was used to quench the excess of isocyanates, yielding the desired products in good purity. A similar concept has been employed in the synthesis of 2-thioxo-4-dihydropyrimidinones using aminomethylated polystyrene beads to quench isothiocyanates as well as aldehydes [48]. To quench an excess of amine in the synthesis of 2,6,9-trisubstituted purines, formyl polystyrene beads were used to form the corresponding polymer-bound imine, which could be filtered off [49]. 

A commercial polystyrene supported version is available — scavenger resin (for diol substrates). 

Polystyrene supports modified with the similar triazine-based dendrons were used by Marsh et al. as insoluble scavengers for removal of excess nucleophilic or electrophilic reagents from the reaction mixtures. Dendrons, decorated with tertiary amines, effectively removed electrophiles (protons), whereas the similar resin with chlorotriazine terminal groups sequestered the excess nucleophiles (amines). 

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