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

doi:10.1055/s-2003-38360

LETTER

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;

Abstract

All articles of this category

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

Full Text

References

1 Corey EJ. Venkateswarlu A. J. Am. Chem. Soc. 1972, 94: 6190

2 Hanessian S. Lavallee P. Can. J. Chem. 1975, 53: 2975

3a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis 3rd ed.: John Wiley and Sons; New York: 1999. p.127-144

3b Clark JH. Chem. Rev. 1980, 80: 429

4a Kelly DR. Roberts SM. Newton RF. Synth. Commun. 1979, 9: 295

4b Collington EW. Finch H. Smith IJ. Tetrahedron Lett. 1985, 26: 681

4c Shimshock SJ. Watermire RE. Deshong P. J. Am. Chem. Soc. 1991, 113: 8791

4d Zhang W. Robins MJ. Tetrahedron Lett. 1992, 33: 1177

4e Corey EJ. Yi KY. Tetrahedron Lett. 1992, 33: 2289

4f Ramasamy KS. Averett D. Synlett 1999, 709

4g Metcalf BW. Burkhart JP. Jund K. Tetrahedron Lett. 1980, 21: 35

4h Ranu BC. Jana U. Majee A. Tetrahedron Lett. 1999, 40: 1985

5a Lee AS. Yeh H. Shie J. Tetrahedron Lett. 1998, 39: 5249

5b Bajwa JS. Vivelo J. Slade J. Repi O. Blacklock T. Tetrahedron Lett. 2000, 41: 6021

5c Oriyama T. Oda M. Gono J. Koga G. Tetrahedron Lett. 1994, 35: 2027

5d Gopinath R. Patel BK. Org. Lett. 2000, 2: 4177

5e Barros MT. Maycock CD. Thomassigny C. Synlett 2001, 1146

5f Kartha KPR. Field RA. Synlett 1999, 311

6a Bartoli G. Bosco M. Marcantoni E. Sambri L. Torregiani E. Synlett 1998, 209

6b Ankala SV. Fenteany G. Tetrahedron Lett. 2002, 43: 4729

6c Farras J. Serra C. Vilarrasa J. Tetrahedron Lett. 1998, 39: 327

6d Grieco PA. Markworth CJ. Tetrahedron Lett. 1999, 40: 665

7a Hunter R. Hinz W. Richards P. Tetrahedron Lett. 1999, 40: 3643

7b Oriyama T. Kobayashi Y. Noda K. Synlett 1998, 1047

7c Lipshutz BH. Keith J. Tetrahedron Lett. 1998, 39: 2495

7d Sabitha G. Syamala M. Yadav JS. Org. Lett. 1999, 1: 1701

7e Paterson I. Cowden CJ. Rahn VS. Woodrow MD. Synlett 1998, 915

8a Mondal E. Bose G. Khan AT. Synlett 2001, 785

8b Mondal E. Bose G. Sahu PR. Khan AT. Chem. Lett. 2001, 1158

8c Khan AT. Boruwa J. Mondal E. Bose G. Indian J. Chem, Sect. B 2001, 40: 1039

8d Mondal E. Sahu PR. Bose G. Khan AT. Tetrahedron Lett. 2002, 43: 2843

8e Mondal E. Sahu PR. Khan AT. Synlett 2002, 463

8f Mondal E. Sahu PR. Bose G. Khan AT. J. Chem. Soc., Perkin Trans. 1 2002, 1026

8g Khan AT. Mondal E. Sahu PR. Islam S. Tetrahedron Lett. 2003, 44: 919

8h Khan AT. Mondal E. Sahu PR. Synlett 2003, 377

9

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

10

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.

11

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.