Catalytic Polymer-Supported Potassium Thiophenolate in Methanol as a Method for the Removal of Ester, Amide, and Thioacetate Protecting Groups

Rachel N. MacCoss; Dara J. Henry; Christopher T. Brain; Steven V. Ley

doi:10.1055/s-2004-817786

LETTER

Catalytic Polymer-Supported Potassium Thiophenolate in Methanol as a Method for the Removal of Ester, Amide, and Thioacetate Protecting Groups

Rachel N. MacCoss^a, Dara J. Henry^a, Christopher T. Brain^b, Steven V. Ley*^a
^a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
e-Mail: svl1000@cam.ac.uk;
^b Novartis Institute for Medical Sciences, 5 Gower Place, London, WC1E 6BS, UK

Abstract

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Abstract

Polymer-supported potassium thiophenolate to remove ester, activated amide, and thioacetate protecting groups catalytically in the presence of methanol is reported.

Key words

polymer-supported - thiophenolate - deprotection

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References

<A NAME="RD27903ST-1">1</A> Greene TW. Wuts PGM. Protective Groups in Organic Synthesis 2nd ed.: Wiley and Sons; New York: 1991.

Argonaut Technologies Catalog 2000, p. 53.

<A NAME="RD27903ST-3">3</A> Ley SV. Baxendale IR. Bream RN. Jackson PS. Leach AG. Longbottom DA. Nesi M. Scott JS. Storer RI. Taylor SJ. J. Chem. Soc., Perkin Trans. 1 2000, 23: 3815

For some recent applications see:

<A NAME="RD27903ST-4A">4a</A> Jamieson C. Congreave MS. Embiata-Smith DF. Ley SV. Synlett 2000, 1603

<A NAME="RD27903ST-4B">4b</A> Jamieson C. Congreave MS. Embiata-Smith DF. Ley SV. Scicinski JJ. Org. Process Res. Dev. 2002, 6: 823

General Procedure: Protected compound (1.0 equiv) was dissolved in MeOH/THF (1:1) in a sealed vial and stirred with thiophenolate resin 1 (1.45 mmol/g, 0.2 equiv). The reaction was heated as described herein. When reaction was complete, the resin was removed by filtration and washed with THF. The combined washings were dried in vacuo. If starting material remained, the product was isolated by standard column chromatography.

Thiophenolate Resin: Polymer-supported thiophenol was shaken at r.t. under argon with potassium trimethylsilanolate in THF. After 2 d, the resin was rinsed with THF and dried in vacuo (1.45 mmol/g).

All compounds gave satisfactory spectroscopic data identical to those reported in the literature.

<A NAME="RD27903ST-8">8</A> Wallace OB. Springer DM. Tetrahedron Lett. 1998, 39: 2693

Resin was filtered, washed with CH₂Cl₂ three times, and dried in vacuo before reusing.