A mild, efficient, inexpensive, and selective cleavage of primary tert-butyldimethylsilyl ethers by oxone in aqueous methanol

Article abstract of DOI:10.1021/ol990140h

(formula presented) The use of a 50% aqueous methonolic solution of Oxone is described for the selective cleavage of primary tert-butyldimethylsilyl and aryl ethers at room temperature. This method enables one to deprotect tert-butyldimethylsilyl ethers of primary alcohols in the presence of tertbutyldimethylsilyl ethers of secondary and tertiary alcohols and phenols. The silyl ethers of phenols were deprotected at longer reaction times.

Full text of DOI:10.1021/ol990140h

ORGANIC
LETTERS
1999
Vol. 1, No. 11
1701-1703
A Mild, Efficient, Inexpensive, and
Selective Cleavage of Primary
tert-Butyldimethylsilyl Ethers by Oxone
in Aqueous Methanol†
Gowravaram Sabitha,* Mandali Syamala, and J. S.Yadav
Indian Institute of Chemical Technology, Hyderabad 500 007, India
gsabithareddy@hotmail.com
Received June 22, 1999
ABSTRACT
The use of a 50% aqueous methonolic solution of Oxone is described for the selective cleavage of primary tert-butyldimethylsilyl and aryl
ethers at room temperature. This method enables one to deprotect tert-butyldimethylsilyl ethers of primary alcohols in the presence of tert-
butyldimethylsilyl ethers of secondary and tertiary alcohols and phenols. The silyl ethers of phenols were deprotected at longer reaction
times.
The tert-butyldimethylsilyl (TBDMS)1 group is one of the
most frequently used protecting groups for the hydroxyl
function in organic synthesis. This is due to easy installa-
tion1,2 and general stability to basic and mildly acidic
reagents.1 Even though a variety of reagents3-11 have been
developed for the cleavage of TBDMS ethers, most of these
methods suffer from the use of basic3 or strong oxidizing7,8
and reducing6 reagents and cumbersome workup. Herein we
report a new method for the selective cleavage of primary
TBDMS ethers by Oxone (KHSO5 triple salt)12 under mild
conditions which can tolerate a wide variety of other
functional groups (Table 1).
Literature shows a number of methods available for the
cleavage of alkylsilyl ethers, but there are only a few methods
reported13 for the cleavage of phenolic TBDMS ethers. Most
of these methods use basic reagents and required elevated
temperatures. Therefore, there still exists a great demand for
a mild reagent which works for the cleavage of alkyl as well
as phenolic TBDMS ethers with selectivity among these two
groups, because the selectivity can be applied to advantage
in complex synthetic sequences in which two protected
hydroxyl groups must be unmasked at different stages of
the synthesis.
†IICT Communication No. 4340.
(1) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190.
(2) (a) Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 20,
99. (b) Corey, E. J.; Cho, H.; Rucker, C.; Hua, D. H. Tetrahedron Lett.
1981, 22, 3455. (c) Lombardo, L. Tetrahedron Lett. 1984, 25, 227.
(3) Corey, E. J.; Snider, B. B. J. Am. Chem. Soc. 1972, 94, 2549.
(4) Pilcher, A. S.; Hill, D. K.; Shimshock, S. J.; Waltermire, R. E.;
DeShong, P. J. Org. Chem. 1992, 57, 2492.
(5) Corey, E. J.; Yi, K. Y. Tetrahedron Lett. 1992, 33, 2289.
(6) Corey, E. J.; Jones, G. B. J. Org. Chem, 1992, 57, 1028.
(7) Tanemura, K.; Suzuki, T.; Horaguchi, T. J. Chem. Soc., Perkin Trans.
1 1992, 2997.
(8) DuttaGupta, A.; Singh. R.; Singh, V. K. Synlett 1996, 69.
(9) Lipshutz, B. H.; Keith, J. Tetrahedron Lett. 1998, 39, 2495.
(10) Oriyama, T.; Kobayashi, Y.; Noda, K. Synlett 1998, 1047.
(11) Bartoli, G.; Bosco, M.; Marcantoni, E.; Sambri, L.; Torrgeiani, E.
Synlett 1998, 209.
(12) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Epifano, F.; Rosati,
O. Synlett 1996, 767.
(13) Crouch, R. D.; Stieff, M.; Frie, J. L.; Cadwallader, A. B.; Bevis, D.
C.; Tetrahedron Lett. 1999, 3133.
10.1021/ol990140h CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/29/1999

Table 1. Deprotection of tert-Butyldimethylsilyl Ethers
Herein we report that potassium monopersulfate available
as Oxone in a 50% aqueous methanolic solution cleaves alkyl
and aryl TBDMS ethers with selectivity under mild condi-
tions.14 The TBDMS ethers of primary alcohols were
deprotected within 2.5-3.0 h whereas the phenolic TBDMS
sulfate and concentrated in rotary evaporator to afford 5-benzyloxypentan-
1-ol in 90% yield, which was identical with the authentic sample. 1H NMR:
TBDMS ether of 5-benzyloxypentan-1-ol (200 MHz, CDCl3) δ 0.02 (s,
6H, SiCH3), 0.85 (s, 9H, Si-t-Bu), 1.35-1.65 (m, 6H, -CH2-), 3.4 (t,
2H, J ) 7 Hz), 3.57 (t, 2H, J ) 7 Hz), 4.45 (s, 2H, ArCH2), 7.26 (m, 5H,
Ar H). 5-Benzyloxypentan-1-ol (200 MHz, CDCl3): δ 1.32-1.7 (m, 6H,
-CH2-), 3.4 (t, 2H, J ) 7 Hz), 3.5-3.63 (m, 2H), 4.5 (s, 2H, ArCH2),
7.15-7.4 (m, 5H, ArH).
(14) General Procedure for the Cleavage of the tert-Butyldimethylsilyl
Group Using Oxone: The TBDMS ether of 5-benzyloxypentan-1- ol (entry
1) (4.32 m mol) was stirred in a 50% aqueous methanolic solution (30 mL)
of Oxone (4.32 m mol) at room temperature for 3 h. The progress of the
reaction was monitored by TLC. On completion the methanol was removed
under reduced pressure and the residue was extracted twice with ethyl
acetate. The combined organic layers were dried on anhydrous sodium
1702
Org. Lett., Vol. 1, No. 11, 1999

ethers were unaffected; with prolonged stirring for 20-24 h
the cleavage was effected. This reveals the selectivity among
alkyl and phenolic TBDMS ethers. On the other hand, the
TBDMS ethers of the secondary and tertiary alcholos were
unaffected by treatment with Oxone. When the reaction was
carried out in the absence of oxidant with 1% dilute HCl
and HF adjusted to the same pH as the Oxone (pH 2.8), the
cleavage of TBDMS group had not occurred after 2.5-3 h.
See comparative data of acid hydrolysis below. Therefore,
revealed. Thus, Oxone is an excellent, inexpensive, and mild
reagent for the selective cleavage of primary alcoholic
TBDMS ethers in the presence of secondary and tertiary
alcohols and phenolic TBDMS ethers.
We have also demonstrated the selective removal of
TBDMS ethers in the presence of tert-butyldiphenylsilyl
(TBDPS) ethers and certain acid-labile protecting groups
(entries 3 and 4) such as THP, N-Boc, etc., and therefore,
this method has advantages over other deprotection meth-
ods.15
In conclusion, we have developed a simple, inexpensive,
selective, and mild procedure for the cleavage of primary
TBDMS ethers which will have a wide scope in view of the
tremendous usefulness of the TBDMS group in organic
synthesis.
OL990140H
(15) (a) Collington, E. W.; Finch, H.; Smith, I. J. Tetrahedron Lett. 1985,
26, 681. (b) Cunico, R. F.; Bedell, L. J. Org. Chem. 1980, 45, 4797.
the real utility of the reagent relative to dilute acids was
Org. Lett., Vol. 1, No. 11, 1999
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