TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8727–8729
A mild and efficient approach for the deprotection of silyl ethers
by sodium periodate
Mijuan Wang, Chun Li, Dali Yin* and Xiao-Tian Liang
Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR
China
Received 10 July 2002; revised 18 September 2002; accepted 26 September 2002
Abstract—A mild and efficient method for the deprotection of silyl ethers is reported. The most often used silyl protecting groups,
such as TBDMS, TIPS, TMS, TES, TIBS, TPS can be cleaved by NaIO4 furnishing the corresponding alcohol in high yields. This
method can be used for a wide range of substrates. © 2002 Elsevier Science Ltd. All rights reserved.
Silyl ethers are the most widely used hydroxyl protect-
ing groups in organic synthesis. Among silylating
reagents, triethylsilyl chloride (TESCl) and tert-
butyldimethylsilyl chloride (TBDMSCl) are often used
as the corresponding silyl ethers are stable towards
various reagents and conditions. The deprotection of
silyl ethers is usually carried out with tetra-
butylammonium fluoride (TBAF),1 aqueous acid,2
aqueous HF–CH3CN3 or various Lewis acids.4 Many
other methods have also been reported including cata-
lytic transfer hydrogenation using Pd,5 reductive cleav-
age by DIBAL-H,6 oxidative cleavage by DDQ7 and
ultrasonic cleavage in MeOH/CCl4,8 together with the
use of PdCl2(CH3CN)2,9 I2,10 K2CO3 in aqueous etha-
nol,11 and chloride ions.12 Herein we report a new mild
and efficient method for the deprotection of silyl ethers.
However, when the pH of the reaction was adjusted to
neutral or slightly basic, the TES and TBDMS groups
were still cleaved. In further investigations, alcohol 2
was used as a model substrate for silyl ether protection
and deprotection because its axial hydroxyl is some-
what hindered and this kind of molecule is so sensitive
to the vanillin/H2SO4 coloring agent that trace amounts
of starting material, product or by-product can easily
be detected on TLC (Scheme 1). The TMS, TES,
TBDMS, TIPS, TIBS, TPS, TBDPS groups were used
as protecting groups to investigate the scope of the silyl
ether deprotection. The protection of alcohol 2 with
various silylating reagents afforded the corresponding
silyl ethers 1 using conventional methods. Silyl ethers 1
were treated with NaIO4 in THF at room temperature
and the reactions were monitored by TLC. After the
usual work-up and chromatography, alcohol 2 (Table
1, entries 1–6) was obtained in high yields.13 However,
the TBDPS groups (Table 1, entries 7 and 8) could not
be removed at room temperature, and gave only low
yields at elevated temperatures after longer reaction
times. The reaction can be performed in either THF/
H2O or aqueous EtOH (Table 1, entry 9; Table 2, entry
6).
We have serendipitously found that TES can be cleaved
by NaIO4 in THF. Because commercial NaIO4 is some-
what acidic, we wondered whether the cleavage of the
Si–O bond was caused by the acidity of the periodate.
In order to investigate the applicability of this method
to different kinds of substrates, we selected a variety of
substrates. Taxanes and a b-lactam (Table 2, entries
1–3) were chosen because they are very sensitive to
acidic conditions. Taxanes and O-TES-N-benzoyl-
phenylisoserine methyl ester (Table 2, entries 2 and 4)
were selected to see if a-hydroxy carbonyl groups can
endure such conditions, as well as phenolic and p-
nitrobenzyl alcohols. The results show that the reac-
Scheme 1.
Keywords: silyl ether; deprotection; sodium periodate.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02138-X