Polystyrene supported scavengers

Fig. 7.10 Polymer-supported scavengers polystyrene-bound diamine (top left), silica-based diamine (top right), Stratosphere Plugs (bottom left), and Synphase Lanterns (bottom right).

Fig. 7.11 Scavenging efficiencies of polymer-supported scavengers (a) polystyrene, (b) functionalized silica, (c) plugs, (d) lanterns] at room temperature (left) and under microwave heating (right).

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

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

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). 

In an opposite manner to bases such as 1 and 2 in terms of reactivity, polymer-supported tosyl chloride equivalent 14 is able to capture alcohols as polymer-bound sulfonates 15, which are released as secondary amines, sulfides and alkylated imidazoles with primary amines, thiols and imidazoles as nucleophiles in a substitution process (Scheme 6) [24]. This technique has further been extended for the preparation of tertiary amines [25] and esters [26]. Excess of amine was scavenged by polymer-supported isocyanate 16 [27, 28] while excess of carboxylic acid was removed by treatment with aminomethylated polystyrene 17. 

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>. 

To understand this effect requires a discussion of the mechanism of autoinitiation. Of the mechanisms proposed, two receive most of the discussion in the literature. A mechanism proposed by Flory [15] involves a 1,4-cyclobutane diradical intermediate and has been supported experimentally by polymerization in the presence of a free radical scavenger. Several of the dimers found in thermally initiated polystyrene are also attributed to a Flory initiation mechanism. 

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]. 

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