Polymer-Supported Thiophenol

Physical Data: loading 1.0-1.5 mmol g-1 (based on benzyl bromide uptake).

Solubility: 1% cross-linked polystyrene backbone is insoluble in all common aqueous and organic solvents.

Form Supplied in: yellow powder; bead size 75-150 mm, 100-200 mesh (95% within). Commercially available; retailer: Argonaut Technologies.1

Purification: the polymer is washed in dichloromethane and dried in vacuo.

Handling, Storage, and Precautions: harmful if inhaled or ingested. Stable at room temperature.

Applications

Polymer-supported thiophenol (PS-thiophenol) has two principal applications in synthetic chemistry; it functions either as a scavenging agent or as a traceless solid-phase linker.2 This functionalized polymer is commonly used as a phase transfer scavenger for a wide range of electrophiles including alkyl halides. It is easy to remove by filtration, thus enabling the preparation of products of high purity without the need for additional purification or isolation procedures. As with all scavenging procedures, 2 or 3 equiv of resin should be used to ensure complete removal of the surplus electrophile. The scavenging ability or nucleophilicity of PS-thiophenol has been found experimentally to be superior to the corresponding benzyl thiol attached to a polystyrene backbone.1 Optimal scavenging results require either the formation of the potassium thiolate salt (formed using potassium trimethylsilylonate) (eq 1)1 or the addition of diisopropylethylamine and mesoporous carbonate (eq 2).1

PS-thiophenol has been utilized in combinatorial library synthesis as an effective and clean method to remove excess electrophilic substrate3 or alkylating reagent (eq 3).4

Another useful application of the resin involves amine deprotection reactions. PS-thiophenol/base can be used to remove the Fmoc protecting group and simultaneously capture the contaminating component (eq 4).5

The reagent can also be used to attach suitable substrates, i.e. molecules susceptible to nucleophilic attack, onto the solid phase and thus facilitate a trivial purification procedure (eq 5).6

While attached to the resin, the isolated moiety can undergo further chemical manipulation with the PS-thiophenol acting as a linker moiety.7 Cleavage is achieved by the addition of an amine (primary or secondary), causing nucleophilic displacement from the resin, which also results in additional modification of the molecule (eq 6). The functionalized polymer acts as a traceless linker without the need for oxidation to the sulfone or sulfoxide.


1. Catalog - Resins and Reagents. Argonaut Technologies, San Carlos, CA, USA, 2000.
2. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J., J. Chem. Soc., Perkin Trans. 1 2000, 23 3815.
3. Ley, S. V.; Massi, A., J. Comb. Chem. 2000, 2, 104.
4. Ermann, M.; Simkovsky, N. M.; Roberts, S. M.; Parry, D. M.; Baxter, A. D.; Montana, J. G., Tetrahedron Lett. 2000, 41, 2483.
5. Katoh, M.; Sodeoka, M., Bioorg. Med. Chem. Lett. 1999, 9, 881.
6. Parrot, I.; Wermuth, C.-G.; Hibert, M., Tetrahedron Lett. 1999, 40, 7975.
7. Sheppeck II, J. E.; Kar, H.; Hong, H., Tetrahedron Lett. 2000, 41, 5329.

Steven V. Ley, D. J. Henry & M. Matsuoka

University of Cambridge, Cambridge, UK



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