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Synlett 2003(5): 0694-0698
DOI: 10.1055/s-2003-38360
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Highly Efficient and Useful Synthetic Protocol for the Cleavage of tert-Butyldimethylsilyl (TBS) Ethers Using a Catalytic Amount of Acetyl Chloride in Dry Methanol

Abu T. Khan*, Ejabul Mondal
Department of Chemistry, Indian Institute of Technology, North Guwahati, Guwahati-781039, Assam, India
Fax: +91(361)2690762; e-Mail: atk@postmark.net;
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Publication History

Received 21 January 2003
Publication Date:
28 March 2003 (online)

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Abstract

A wide variety of tert-butyldimethylsilyl (TBS) ethers as well as tert-butyldiphenylsilyl (TBDPS) ethers 1 can be easily deprotected to the corresponding parent hydroxyl compounds 2 by employing catalytic amounts of acetyl chloride in dry MeOH at 0 °C to room temperature in good yields. Some of the major advantages are mild conditions, high efficiency, high selectivity, high yields, easy operation, and also compatibility with other protecting groups. Furthermore, no acetylation nor chlorination takes place under the experimental conditions.

Key words

deprotection - tert-butyldimethylsilyl (TBS) ethers - tert-butyldiphenylsilyl (TBDPS) ethers - acetyl chloride

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Khan, A. T.; Mondal, E. unpublished results.

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A Typical Procedure for Deprotection: To a stirred solution of silylated compound 1 (1 mmol) in dry MeOH (3 mL) was added AcCl (11 µL, 0.15 mmol) at ice-bath temperature. The reaction mixture was stirred at ice-bath temperature or r.t. depending upon the substrate (see Table [1] ). After completion of the reaction (monitored by TLC), CH2Cl2 was added (20 mL), the reaction mixture was neutralized with 10% NaHCO3 (1 mL) and washed with H2O (10 mL). Finally, the organic layer was dried (Na2SO4) and concentrated in vacuo to give a ‘crude’ residue, which was purified on silica gel column chromatography. The final desired products were obtained in good to excellent yields.

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Spectroscopic data for compound 1i:
1H NMR (CDCl3, 200 MHz): δ = 0.01 [s, 6 H, Si(CH3)2], 0.85 [s, 9 H, SiC(CH3)3], 1.19-1.60 (m, 18 H, -CH2), 2.25 (t, 2 H, J = 7.3 Hz, -CH 2CO2CH3), 3.55 (t, 2 H, J = 6.4 Hz,
-CH 2OTBS), 3.62 (s, 3 H, CO2CH 3). Anal. Calcd for C19H40O3Si: C, 66.22; H, 11.70. Found: C, 66.01; H, 11.65. For compound 2i: 1H NMR (CDCl3, 200 MHz): δ = 1.20-1.70 (m, 18 H, -CH2-), 1.80 (br s, 1 H, OH, D2O exchangeable), 2.30 (t, 2 H, J = 6.8 Hz, -CH 2CO2CH3), 3.63 (t, 2 H, J = 5.9 Hz, -CH 2OH), 3.67 (s, 3 H, CO2CH3). Anal. Calcd for C13H26O3: C, 67.78; H, 11.38. Found: C, 67.52; H, 11.26. For compound 1v: 1H NMR (400 MHz, CDCl3): δ = 0.01 [s, 3 H, Si(CH3)2], 0.02 [s, 3 H, Si(CH3)2], 0.85 [s, 9 H, SiC(CH3)3], 1.25 (t, 3 H, J = 7.3 Hz, SCH2CH 3], 2.63-2.71 (m, 2 H, SCH 2CH3), 3.21-3.24 (m, 1 H, H-5), 3.46 (t, 1 H, J = 9.0 Hz, H-3), 3.56 (t, 1 H, J = 9.3 Hz, H-2), 3.61 (t, 1 H, J = 9.0 Hz, H-4), 3.75 (dd, 1 H, J = 3.8 Hz, J = 11.2 Hz, H-6), 3.80 (dd, 1 H, J = 2.0 Hz, J = 11.7 Hz, H-6′), 4.38 (d, 1 H, J = 9.8 Hz, H-1), 4.62 (d, 1 H, J = 10.2 Hz, -OCHPh), 4.68 (d, 1 H, J = 10.2 Hz, OCHPh), 4.79 (dd, 2 H, J = 4.6 Hz, J = 10.7 Hz, OCH2Ph), 4.85 (dd, 2 H, J = 4.0 Hz, J = 10.3 Hz, OCH2Ph), 7.19-7.33 (m, 15 H, ArH). 13C NMR: δ =
-5.37, -5.04, 15.19, 18.30, 24.34, 25.89 (3 C), 62.30, 75.06, 75.46, 75.87, 77.68, 80.03, 81.83, 84.40, 86.62, 127.69, 127.81, 127.93, 128.00, 128.29, 128.38, 128.46, 138.09, 138.32, 138.52. Anal. Calcd for C35H48O5SSi: C, 69.04; H, 7.94, S, 5.26. Found: C, 69.35; H, 7.85; S, 5.01. For compound 2v: 1H NMR (400 MHz, CDCl3): δ = 1.32 (t, 3 H, J = 7.3 Hz, SCH2CH 3), 1.95 (br s, 1 H, OH, D2O exchangeable), 2.71-2.80 (m, 2 H, SCH 2CH3), 3.35-3.39 (m, 1 H, H-5), 3.41 (t, 1 H, J = 9.3 Hz, H-3), 3.58 (t, 1 H, J = 9.3 Hz, H-2), 3.70 (t, 1 H, J = 8.8 Hz, H-4), 3.87 (d, 1 H, J = 11.5 Hz, -OCHPh), 4.50 (d, 1 H, J = 9.8 Hz, H-1), 4.65 (d, 1 H, J = 11 Hz, -OCHPh), 4.74 (d, 1 H, J = 11 Hz, OCHPh), 4.86 (d, 2 H, J = 12.4 Hz, -OCH 2Ph), 4.89 (d, 1 H, J = 10.0 Hz, -OCHPh), 4.92 (dd, 2 H, J = 6.8 Hz, J = 11 Hz, H-6, H-6′), 7.25-7.38 (m, 15 H, ArH). 13C NMR: δ = 15.16, 25.20, 62.15, 75.17, 75.57, 75.74, 75.76, 77.69, 79.27, 81.77, 85.27, 86.47, 127.71, 127.77, 127.89, 127.96, 128.07, 128.29, 128.41, 128.46, 128.52, 137.90 (2 C), 138.41. Anal. Calcd for C29H34O5S: C, 70.42; H, 6.93, S, 6.48. Found: C, 70.20; H, 6.86; S, 6.24. For compound 1x: 1H NMR (CDCl3, 300 MHz) δ = 0.07 [s, 6 H, Si(CH3)2], 0.90 [s, 9 H, SiC(CH3)3], 1.33 [s, 6 H, =C(CH3)2], 1.44 (s, 3 H, =CCH3), 1.54 (s, 3 H, =CCH3), 3.70-3.86 (m, 3 H, H-2, H-3, H-5), 4.30 (dd, 2 H, J = 2.3 Hz, J = 7.2 Hz, H-4, H-6), 4.60 (dd, 1 H, J = 1.6 Hz, J = 7.9 Hz, H-6′), 5.52 (d, 1 H, J = 4.9 Hz, H-1). Anal. Calcd for C18H34O6Si: C, 57.72; H, 9.15. Found: C, 57.55; H, 9.03. For compound 2x: 1H NMR (CDCl3, 300 MHz): δ = 1.34 [s, 6 H, =C(CH3)2], 1.46 (s, 3 H, =CCH3), 1.54 (s, 3 H, =CCH3), 2.28 (br s, 1 H, OH, D2O exchange-able), 3.75 (t, 1 H, J = 7.3 Hz, H-4), 3.82-3.90 (m, 2 H, H-2 and H-5), 4.27 (d, 1 H, J = 7.9 Hz, H-3), 4.34 (dd, 1 H, J = 2.3 Hz, J = 4.9 Hz, H-6), 4.62 (dd, 1 H, J = 2.3 Hz, J = 7.9 Hz, H-6′), 5.57 (d, 1 H, J = 5.0 Hz, H-1). Anal. Calcd for C12H20O6: C, 55.37; H, 7.74. Found: C, 55.48; H, 7.69.