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Chemistry Letters Vol.32, No.7 (2003)
A Mild, Efficient and Selective Cleavage of Aryl tert-Butyldimethysilyl Ethers
Using KOH in Ethanol
Zhi-Yong Jiang and Yan-Guang WangÃ
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
(Received March 4, 2003; CL-030181)
An efficient and selective method for the deprotection of
that the rate of deprotection of aryl TBS ethers was accelerated
if an electron-withdrawing group was present on the aromatic
ring (Table 1, Entries 1–3). On the other hand, the presence
of an electron-donating group on the aromatic ring decelerated
the desired transformation (Table 1, Entries 8–9).
aryl tert-butyldimethysilyl (TBS)ethers is described. The pro-
tecting group TBS could be cleaved from aryl silyl ethers in
the prensence of alkyl TBS ethers using KOH in ethanol at
room temperature to give the corresponding phenols in excel-
lent yields (87–99%).
Table 1. Deprotection of aryl and alkyl TBS ethers to phenols
and alcohols using 1.5 equiv. solid KOH in ethanol
Reaction
time/h
The chemical manipulation of complex polyfunctional mo-
lecules often requires the sequential protection and deprotection
of the various functionalities. Silyl ethers have attained a posi-
tion of prominence in the area of hydroxyl group protection due
to their easy formation and removal and their stability to a wide
range of reagents and reaction conditions.1 Among silyl ethers,
tert-butyldimethysilyl (TBS)is the most popular because it can
be easily installed in high yields and is robust to a variety of re-
action conditions.1
Entry
Silyl ethers
Yield/%a
1
2
3
4
5
6
7
8
9
4-ClC6H4OTBS
4-CHOC6H4OTBS
2-CHOC6H4OTBS
C6H5OTBS
4-MeC6H4OTBS
4-t-BuC6H4OTBS
2-MeC6H4OTBS
3-NH2C6H4OTBS
4-MeOC6H4OTBS
C6H5CH2OTBS
n-C8H17OTBS
0.3
0.3
0.5
0.7
1.0
1.0
1.6
2.0
2.0
18
99
98
98
95
92
97
93
It is very important to seek a mild reagent to deprotect aryl
TBS ethers in the presence of alkyl TBS ethers, since the selec-
tivity can be applied to advantage in complex synthetic se-
quences in which one of two protected hydroxyl groups must
be unmasked at different stages of the synthesis. Although cam-
phorsulfonic acid/methanol2 and aqueous DMSO3 have been
used to cleave aryl TBS ethers in the presence of alkyl TBS
ethers, a survey of the methods reported to effect selective de-
silylation of aryl silyl ethers reveals basic conditions to be the
norm.4 Davies has demonstrated that, while the desilylation of
the TBS ether of p-cresol in 5% NaOH has a half-life of
3.5 min, the TBS ether of n-hexanol is stable over 24 h.5 Among
the systematically studied basic regents reported to effect selec-
tive removal of silyl groups from phenols are: TBAF/THF,6;7
KF/18-crown-6,7 KF/alumina/ultrasound,8 K2CO3/kryptofix/
CH3CN,9 K2CO3/ ethanol,10 NaOH/n-Bu4NHSO4/dioxane,11
KF/alumina,12 and LiOH/DMF.13 Other methods employing
TBAF have been reported as parts of total syntheses.14{17 Some
of these methods require elevated reaction temperature,3;9;10
lengthy reaction times.3;7 using large amounts of base.11;13
Herein we report a new method for the selective cleavage of
phenol TBS ethers using KOH in ethanol at room temperature
in relative short time, which utilizes conventional laboratory re-
agents and equipment, does not require an aqueous workup, and
tolerate a wide variety of other functional groups.
91
87
10
11
12
23
No reaction
No reaction
24
24
i-C8H17OTBS
a.Isolated yield.
To establish the chemoselectivity of this method, the aryl
silyl ethers containing alkyl silyl ethers and other sensitive
groups were allowed to cleave in ethanol in the presence of
1.5 equiv. of KOH at room temperature (Scheme 1), and the re-
sults are summarized in Table 2. The aryl silyl ethers could be
deprotected cleanly to give corresponding phenols in very high
yields, while TBS-protected alcohols (Table 2, Entries 1–4),
carboxylic esters (Table 2, Entries 5–6), and tetrahydropyranyl
(THP)-protected alcohol (Table 2, Entry 7) were unscathed un-
der these conditions.
In summary, we have developed a simple, inexpensive, se-
lective and mild procedure for the cleavage of aryl silyl ethers
in the presence of alkyl silyl ethers using 1.5 equiv. of KOH in
ethanol. The reaction conditions can also allow selective depro-
tection of aryl TBS-protected phenols in the presence of phenyl-
oxycarbonyl or tetrahydropyranyl-protected alcohols.
This work was financially supported by the National Natur-
al Science Foundation of China (No. 20272051)as well as the
Investigation of reaction conditions for the cleavage of aryl
silyl ethers using KOH demonstrated that 1.5 equiv. of KOH in
ethanol at room temperature was optimal for the desired depro-
tection. We examined a variety of substrates including aryl TBS
ethers and alkyl desired deprotection.18 As shown in Table 1,
aryl TBS ethers could be cleaved smoothly (Table 1, Entries
1–9), while benzyl and alkyl had poor yield or no reaction in
the same conditions (Table 1, Entries 10–12). We also observed
R2
R2
1.5 equiv. KOH
ethanol, rt
R1
OH
R1
OTBS
Scheme 1.
Copyright Ó 2003 The Chemical Society of Japan
Jiang, Zhi-Yong
