Chemoselective and practical deprotection of alkyl trialkylsilyl ethers in the presence of aryl trialkylsilyl ethers by a catalytic amount of Sc(OTf)3

Article abstract of DOI:10.1055/s-1998-1890

Treatment of alkyl trialkylsilyl ethers with 0.5 mol% of Sc(OTf)₃ combined with 5 equivalents of water in acetonitrile provides an efficient and practical method for the deprotection of silyl ethers. Alcoholic trialkylsilyl ethers have been cleaved selectively in the presence of phenolic trialkylsilyl ethers.

Full text of DOI:10.1055/s-1998-1890

October 1998
SYNLETT
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Chemoselective and Practical Deprotection of Alkyl Trialkylsilyl Ethers in the Presence of
Aryl Trialkylsilyl Ethers by a Catalytic Amount of Sc(OTf)3
Takeshi Oriyama,* Yoshinobu Kobayashi, and Kojiro Noda
Department of Environmental Sciences, Faculty of Science, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512, Japan
Received 30 June 1998
Abstract: Treatment of alkyl trialkylsilyl ethers with 0.5 mol% of
yield by employing only 0.5 mol% of Sc(OTf) (Table 2, Runs 1, 2, and
3
Sc(OTf) combined with 5 equivalents of water in acetonitrile provides
3). On the other hand, the reactions of more sterically bulky silyl ethers,
triisopropylsilyl (TIPS) ether and t-butyldiphenylsilyl (TBDPS) ether,
did not proceed smoothly under comparable reaction conditions. Longer
3
an efficient and practical method for the deprotection of silyl ethers.
Alcoholic trialkylsilyl ethers have been cleaved selectively in the
presence of phenolic trialkylsilyl ethers.
reaction time (24 h) and/or usage of a larger amount of Sc(OTf) (10
3
mol%) gave the parent alcohols in 97% and 93% yield, respectively
(Runs 4 and 6).
Trialkylsilyl ether is a very important hydroxyl protecting group in
synthetic organic chemistry and various silyl ethers have been devised
1
and extensively utilized in synthetic sequences of complex natural
2
products. t-Butyldimethylsilyl ethers are one of the most commonly
used trialkylsilyl ethers and are very easy to introduce and to remove. A
1
variety of reagents exist for its removal, and very recently several
methods for the deprotection of silyl ethers under various reaction
3
conditions have been reported in the literature. However, only scattered
procedures for the selective cleavage of alkyl silyl ethers over aryl silyl
3d,4
ethers have been reported.
On the other hand, scandium
trifluoromethanesulfonate (Sc(OTf) ) was discovered by Kobayashi et
3
5
al. to be a new type of water-soluble Lewis acid, and many useful
reactions using Sc(OTf) have been developed.
6
3
In this paper we report a highly selective and convenient procedure for
the new deprotection of trialkylsilyl ethers using a catalytic amount of
Sc(OTf) .
3
First, we attempted the reaction of t-butyldimethylsilyl ether of 3-
phenylpropanol with 0.5 mol% of Sc(OTf) in acetonitrile. After 1 h,
3
usual work-up of the reaction mixture gave the corresponding alcohol in
48% yield. Screening the amount of water in the reaction revealed that 5
equivalents of water gave the best result as shown in Table 1 (Runs 1, 2,
3, and 4).
The deprotection was conducted with various TBS ethers of primary,
secondary, and phenolic alcohols and the results are collected in Table
7
3. Although the deprotection of aliphatic TBS ethers showed
considerable success, phenolic TBS ethers remained unchanged with the
recovery of the starting TBS ethers. The reaction of TBS ether of p-
bromophenol with 1.5 mol% of TfOH for 6 h afforded the p-
bromophenol in 62% yield, which means the actual species of this
deprotection of aliphatic silyl ethers is not TfOH.
Finally, we examined the chemoselective deprotection of aliphatic TBS
ether in the presence of phenolic TBS ether and the result was very
satisfactory as shown in Scheme 1. Similar chemoselective deprotection
was also successful with the TBDPS group, that is, between aliphatic
TBDPS ether and aromatic TBDPS ether (Scheme 2). Additionally,
more subtle intermolecular chemoselectivity of deprotection between
TBS ether and TBDPS ether of a secondary alcohol was also
successfully performed as shown in Scheme 3.
The salient features of the present deprotection of trialkylsilyl ethers
include: 1) the ease of operation 2) high efficiency 3) mild reaction
conditions 4) chemoselectivity. The deprotection of aliphatic
trialkylsilyl ethers described here adds a new and convenient method for
the chemistry of protecting groups.
Next, we examined the effect of the trialkylsilyl moiety of silyl ethers.
In the case of trimethylsilyl (TMS), triethylsilyl (TES), and t-
butyldimethylsilyl (TBS) ether, the deprotection was completed within 1
h at room temperature to give the corresponding alcohols in excellent

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SYNLETT
Scheme 3
Acknowledgment. This work was partially supported by the Uehara
Memorial Foundation.
References and Notes
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd Ed., John Wiley & Sons : New York, 1991;
Kocienski, P. J. Protecting Groups, Georg Thieme Verlag : New
York, 1994.
(2) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc., 1972, 94,
6193.; Corey, E. J.; Snider, B. B. J. Am. Chem. Soc., 1972, 94,
2549.; Corey, E. J.; Cho, H.; Rücker, C.; Hua, D. H. Tetrahedron
Lett., 1981, 22, 3455.
(3) (a) Wilson, N. S.; Keay, B. A. Tetrahedron Lett., 1997, 38, 187. (b)
Maiti, G.; Roy, S. C. Tetrahedron Lett., 1997, 38, 495. (c) Farràs,
J.; Serra, C.; Vilarrasa, J. Tetrahedron Lett., 1998, 39, 327. (d)
Lipshutz, B. H.; Keith, J. Tetrahedron Lett., 1998, 39, 2495. (e)
Bartoli, G.; Bosco, M.; Marcantoni, E.; Sambri, L.; Torregiani, E.
Synlett, 1998, 209.
(4) Collington, E. W.; Finch, H.; Smith, I. J. Tetrahedron Lett., 1985,
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(6) Hachiya, I.; Kobayashi, S. J. Org. Chem., 1993, 58, 6958.;
Kawada, A.; Mitamura, S.; Kobayashi, S. Synlett, 1994, 545.;
Kobayashi, S. Synlett, 1994, 689.; Kobayashi, S.; Ishitani, H.;
Nagayama, S. Synthesis, 1995, 1195.; Ishihara, K.; Kubota, M.;
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(7) Typical experimental procedure is as follows (Table 3, Run 4): To
a solution of scandium trifluoromethanesulfonate (6.4 mg, 0.013
Scheme 1
mmol) in CH CN (15 ml) was added 1-(1,1-dimethyl-
3
ethyl)dimethylsiloxy-3-phenylpropane (3.23 g, 12.9 mmol) in
CH CN (50 ml) and water (1.15 ml, 63.8 mmol) at room
3
temperature. The resultant mixture was stirred for 12 h at room
temperature and quenched with a phosphate buffer (pH 7). The
organic materials were extracted with dichloromethane (3 x 20
ml) and the combined extracts were washed with brine and dried
over anhydrous sodium sulfate. The solvent was evaporated and 3-
phenylpropanol (1.72 g, 98%) was isolated by column
chromatography on silica gel (ether : hexane = 1 : 1). The product
Scheme 2
1
gave satisfactory H NMR and IR spectra.