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Deprotection of a tert-butyldimethylsilyl ether; alcohol

SyntheticPage 132
DOI: 10.1039/SP132
Submitted Aug 24, 2001, published Aug 24, 2001
Melanie Reich (m.t.reich@sussex.ac.uk)
A contribution from Caddick, Sussex


			Reaction Scheme: <IMG src="/images/empty.gif">Deprotection of a tert-butyldimethylsilyl ether<IMG src="/images/empty.gif">

Chemicals Used

silyl ether (prepared, 1 equiv.),
tetrahydrofuran (distilled from sodium-benzophenone ketyl, 100 mL/mmol),
tetra-n-butylammonium fluoride (TBAF) (Aldrich, 1 M solution in THF (contains 4.5-5 % water), 1.1 equiv.),
dichloromethane (GPR, 20 mL/mmol),
water (5 mL/mmol),
brine (5 mL/mmol)

Procedure

To a cold (0 ÂșC) solution of the silyl ether (460 mg, 1.16 mmol, 1 equiv.) in dry tetrahydrofuran (11.6 mL), was added tetra-n-butylammonium fluoride (TBAF) (1.3 mL of a 1 M solution in tetrahydrofuran, 1.27 mmol, 1.1 equiv.) and the resulting solution stirred for 45 minutes allowing the mixture to warm to room temperature. The resulting solution was diluted with dichloromethane (20 mL) and quenched with water (5 mL). The organic layer was extracted with brine (5 mL) and dried over magnesium sulfate, followed by solvent reduction in vacuo. The crude product was purified by flash column chromatography (petroleum ether/ethyl acetate, 5 : 1 to 3 : 1) to give the alcohol as a white powder (106 mg, 32 %).

Author's Comments

This reaction was only carried out a couple of times, on a 100 to 500 mg scale, however only in low yields, with no starting material recovered. Decomposition and thus low yields are thought to be caused by the basicity of TBAF. Therefore buffering the reagent with acetic acid or use of buffered HF (HF.pyridine) should limit degradation and improve yields considerably. Is the compound to be deprotected not base sensitive, then TBAF is a good reagent; however, when sensitive functional groups are present a buffered reagent should be used.

Data

1H NMR (300 MHz; (CD3)2CO) 11.76 (1 H, s, OH (naph.) [exch]), 8.74 (1 H, dd, J 8.5 and 1.0, naph.), 8.10 (1 H, d, J 9.0, naph.), 7.89 (1 H, dd, J 8.5 and 1.5, naph.), 7.86 (1 H, dd, J 6.5 and 2.0, cyclop.), 7.59 (1 H, ddd, J 8.5, 7.0 and 1.5, naph.), 7.41 (1 H, ddd, J 8.5, 7.0 and 1.0, naph.), 7.22 (1 H, d, J 9.0, naph.), 6.50 (1 H, dd, J 6.5 and 2.0, cyclop.), 6.18 (1 H, q, J 2.0, cyclop.), 5.26 (1 H, d, J 5.5, OH (cyclop.) [exch]), 4.69 (1 H, dd, J 5.5 and 2.0, cyclop.)

Lead Reference

J. H. Clark, Chem. Rev., 1980, 80, 429 doi:10.1021/cr60327a004
E. J. Corey, A. Venkateswarlu, J. Am. Chem. Soc., 1972, 94, 6190 doi:10.1021/ja00772a043

Other References

A. B. Smith, III, G. R. Ott, J. Am. Chem. Soc., 1996, 118, 3095 (TBAF/AcOH)
K. C. Nicolaou, S. E. Webber, Synthesis, 1986, 453 (HF.py) doi:10.1055/s-1986-31673

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Keywords: 132, cyclopentenone, deprotection, hydroxy, removal, TBAF, TBDMS, TBS, tetrabutylammonium fluoride

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