Tetrahedron Letters
Chemoselective deprotection of silyl ethers by DIBALH
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Takefumi Kuranaga, Shuji Ishihara, Naohito Ohtani, Masayuki Satake , Kazuo Tachibana
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The first examples of highly selective deprotection of silyl ethers by DIBALH are reported. Its selectivity
Received 30 August 2010
Revised 21 September 2010
Accepted 27 September 2010
Available online 7 October 2010
enabled us to remove a primary TBS group and a primary TBDPS group in the presence of a secondary TES
group.
Ó 2010 Elsevier Ltd. All rights reserved.
Protection and deprotection of functional groups, especially hy-
droxy groups, are important steps in organic synthesis, and numer-
ous protective groups have been reported with their formation and
cleavage methods.1
TES group, TBS group, and TBDPS group were also smoothly
cleaved at lower temperature. On the other hand, the secondary
TES ethers 36 and 57 were not cleaved and their benzylidene ace-
tals were reduced regioselectively8 with DIBALH at higher temper-
ature (0 °C to rt, entries 4 and 5). These differences in reactivity
between primary silyl ethers and secondary silyl ethers encour-
aged us to use DIBALH for selective deprotection.
Next, we investigated the selective deprotection of 1,3-bis-silyl
ethers, which were synthesized from a known diol 79,10 (Table 2).
Treatment of bis-TBS ether 8a with 5 equiv of DIBALH afforded
78% yield of the primary alcohol 9a. It is noteworthy that the selec-
tive deprotection of 8a under the usual conditions failed. Selective
deprotections using acids (CSA, PPTS, and AcOH) failed because of
the competitive deprotection of the benzylidene acetal. Low selec-
tivity was observed in the deprotection using TBAF. The benzyli-
dene acetal was more stable than the primary TBS group under
this condition. Similarly bis-TES ether 8b was converted to the pri-
mary alcohol 9b in 80% yield (entry 2).
Next, we investigated the deprotection of a primary TBS group
and a primary TBDPS group in the presence of a secondary TES
group. It is well known that the TBS ether and the TBDPS ether
are more stable than the TES ether under the usual deprotection
reaction conditions. For this reason, no general method of selective
deprotections of a primary TBS group and a primary TBDPS group
in the presence of a secondary TES group had been previously re-
ported.3 Interestingly, when the silyl ethers 8c and 8d were treated
with DIBALH, primary alcohol 9b was afforded in good yield (en-
tries 3 and 4). The secondary TES ether remained unaltered under
these conditions even though a primary TBS group and a primary
TBDPS group were smoothly removed. When the reaction was
run with 2 equiv of DIBALH, a longer reaction time was required
(entry 5). Although we conducted the reactions in CH2Cl2, we did
not find any remarkable difference using toluene (entry 6).
We then studied the scope and limitations of this efficient selec-
tive deprotection (Table 3). The deprotection of 1,4-bis-silyl ethers
10a–d11 (entries 1–4) and 1,2-bis-silyl ether 1412 (entry 5) are
shown in table 3. Treatment of bis-TBS ether 10a with DIBALH at
ꢀ20 °C gave the desired primary alcohol 11a in 57% yield with
Silyl ethers, such as the TES (triethylsilyl) group, the TBS (tert-
butyldimethylsilyl) group, and the TBDPS (tert-butyldiphenylsilyl)
group are the most widely used protective groups for alcohols be-
cause of the facility for selective protection and deprotection.
Selective introduction of silyl ethers is achieved by controlling
the reaction conditions, for example, the solvent, temperature,
reaction time, base, amount of the reagents, and so on. Similarly,
many groups reported selective deprotection of silyl ethers by
proper choice of the conditions.2 The steric hindrance around the
silicon atom and the alcohol influences the reactivity of protection
and cleavage.
In general, silyl ethers are effectively cleaved by acid, base, or a
fluoride anion. On the other hand, a lot of unexpected deprotec-
tions of silyl ethers also have been reported. For example, many
groups reported the deprotection of silyl ethers by DIBALH (diiso-
butylaluminium hydride)3 as unexpected side-reactions from the
use of this electrophilic reducing agent.4
In our synthetic studies, we also have experienced this
undesired deprotection of silyl ethers by DIBALH even at low
temperatures. However, we found that this undesired deprotection
occurred mainly for primary silyl ethers, while secondary silyl
ethers were often stable even at higher temperatures (0 °C to rt).
Based on these observations, we investigated the use of DIBALH
for the selective deprotection of primary silyl ethers in the pres-
ence of secondary silyl ethers.
Firstly, we examined the deprotection of silyl ethers by DIBALH
under various conditions (Table 1). Treatment of primary silyl
ethers 1a–c with DIBALH at ꢀ20 °C afforded primary alcohol 2 in
good yields5 (entries 1–3). Originally, the deprotection of the TBS
group at room temperature was reported though, the primary
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Corresponding authors. Tel.: +81 3 5841 4357; fax: +81 3 5841 8380 (M.S.).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.