A high loading sulfonic acid-functionalized ordered nanoporous silica as an efficient and recyclable catalyst for chemoselective deprotection of tert-butyldimethylsilyl ethers

Article abstract of DOI:10.1016/j.tetlet.2005.04.100

A high loading sulfonic acid-functionalized ordered nanoporous silica efficiently catalyzes the deprotection of a variety of alcoholic TBDMS (tert-butyldimethylsilyl)ethers in methanol. The catalyst shows high thermal stability (up to 240°C) and can be recovered and reused for at least seven reaction cycles without loss of reactivity. This method can be used to deprotect TBDMS ethers of alcohols in the presence of TBDMS ethers of phenols.

Full text of DOI:10.1016/j.tetlet.2005.04.100

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4661–4665
A high loading sulfonic acid-functionalized ordered
nanoporous silica as an efficient and recyclable catalyst for
chemoselective deprotection of tert-butyldimethylsilyl ethers
a,b,
a
*
Babak Karimi
and Daryoush Zareyee
a
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), PO Box 45195-1159, Gava Zang, Zanjan, Iran
b
Institute for Fundamental Research (IPM), Farmanieh, PO Box 19395-5531, Tehran, Iran
Received 8 February 2005; revised 17 April 2005; accepted 26 April 2005
Available online 23 May 2005
Abstract—Ahigh loading sulfonic acid-functionalized ordered nanoporous silica efficiently catalyzes the deprotection of a variety of
alcoholic TBDMS (tert-butyldimethylsilyl)ethers in methanol. The catalyst shows high thermal stability (up to 240 °C) and can be
recovered and reused for at least seven reaction cycles without loss of reactivity. This method can be used to deprotect TBDMS
ethers of alcohols in the presence of TBDMS ethers of phenols.
Ó 2005 Elsevier Ltd. All rights reserved.
2
0
The role of silyl groups has been recognized as an
important part of organic chemistry from both analyti-
cal and synthetic points of view, for example, as protect-
Other milder reagents such as LiCl, carboxylic acid
2
1
22
23
+
resins, organotin reagents, I , n-Bu N Br3 ,
À 24
2
4
2
5
NIS, and acetonyl triphenylphosphonium bromide
26
1
ing groups in many syntheses of reasonable complexity.
(ATPB)
have also been developed to desilylate
tert-Butyldimethylsilyl (TBDMS) ethers are among the
most frequently used protective groups for alcohols, be-
cause they can be easily installed in high yields and can
TBDMS ethers under mild reaction conditions.
Although, these methods are useful in many synthetic
transformations, most of them suffer from limitations
such as prolonged reaction times, formation of side
products, the use of expensive catalysts, cumbersome
work-up procedures, and the use of non-recyclable and
sensitive catalysts. Therefore, it seems that there is much
room for the development of new protocols to circum-
vent these problems.
2
withstand a wide variety of reaction conditions.
Although, the major goal of such a protection is usually
to prevent unfavorable reactions of hydroxyl groups, in
many cases it is often necessary to convert selectively the
3
silyl ethers to their corresponding parent alcohols. The
usual procedure for deprotection of TBDMS ethers in-
+
volves the use of n-Bu N F .
À 2a,4
However, fluoride-
4
based protocols suffer from some disadvantages such
as high cost of the reagent and incompatibility with
base-sensitive substrates owing to the high basicity of
fluoride ions, which can cause side reactions. Thus,
many alternative and mild protocols have been reported
for the deprotection of silyl ethers and Lewis acid-based
Increasing awareness of the environmental costs of
traditional acid-catalyzed chemical transformations has
created an opportunity for new solid acid-based ap-
proaches for many important laboratory and industrial
5
2
7–31
reactions.
Solid acids offer simpler and more benign
alternatives than their homogeneous counterparts.
However, to maintain economic viability, a suitable het-
erogeneous system must not only minimize the produc-
tion of waste, but should also exhibit high stability,
activities, and selectivities comparable or superior to
the existing homogeneous routes. Polymer-supported
catalysts have been widely used in research and in pro-
cess chemistry due to easy recovery, however their use
is restricted because of easy damage to the organic use
6
7
8
9
protocols using TMSOTf, TMSCl, BF ÆOEt , BCl ,
3
13
2
3
1
0
11
12
14
Sc(OTf)3, InCl , ZnBr2, Zn(BF ) , Ce(OTf) ,
5
3
1
4 2
17
4
16
18
CeCl Æ7H O/NaI, BiBr3, BiOClO4, SbCl5, and
3
2
1
9
ZrCl4, which have been developed for this purpose.
Keywords: Solid acids; Protecting groups; Solid sulfonic acids; TBD-
MS ethers; Catalysts.
3
2
*
Corresponding author. Tel.: +98 241 4153225; fax: +98 241
249023; e-mail: karimi@iasbs.ac.ir
polymer backbone (thermal or chemical). One way
to overcome this problem of the traditional polymer
4
0
040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.100

4662
B. Karimi, D. Zareyee / Tetrahedron Letters 46 (2005) 4661–4665
supported catalysts is to change the expensive organic
polymer chain to a silica chain having a covalently
anchored organic spacer to create organic–inorganic
the TBDMS ether. We observed that the reaction was
completed within 90 min and pure benzyl alcohol was
obtained in 94% isolated yield (Table 1, entry 1).
3
3
hybrid (interphase) catalysts. In this type of solid,
the reactive centers are highly mobile similar to that of
homogeneous catalysts and at the same time it has the
advantage of recyclability of the heterogeneous cata-
lysts. Based on this idea, several types of sulfonic acid-
functionalized silica have been synthesized and applied
as alternatives to traditional sulfonic resins in catalyzing
This result led us to examine the scope of this reaction
for the deprotection of other silylated compounds. Our
results show that the method is general for the cleavage
of TBDMS ethers of primary (Table 1, entries 1–6), sec-
ondary (entries 7–13), allylic (entry 14), and hindered,
acid sensitive secondary (entry 15) TBDMS ethers. We
have also found that under similar reaction conditions
even TBDMS-protected tertiary alcohols undergo
deprotection to produce modest yields of the corre-
sponding alcohols but longer reaction times were re-
quired than for less sterically hindered substrates
(entries 16 and 17). Moreover, no elimination product
was detected during the course of deprotection of ter-
tiary TBDMS ethers (Table 1, entries 16 and 17). Inspec-
tion of the data in Table 1 also shows that the reaction
conditions are mild enough to allow a C@C double
bond to remain unaffected (entry 14). It should be noted
that phenolic TBDMS ethers and tert-butyldiphenylsilyl
(TBDPS) ethers (entries 18–20) are stable under the
reaction conditions even when increasing the time or
amount of catalyst 1. This observation encouraged us
to study the chemoselective deprotection of alcoholic
TBDMS ethers in the presence of either TBDPS-pro-
tected alcohols or phenolic TBDMS ethers in competi-
tive experiments. Indeed, our results show that this
method is useful for the selective cleavage of alcoholic
TBDMS ethers in the presence of TBDMS-protected
phenols (Scheme 3).
3
4
chemical transformations. Among the different types
of silica-based sulfonic acids, recently, Stein and his
co-workers have prepared a novel sulfonic functional-
ized ordered microporous silicate, which shows high
loading, high stability, and yet uniform nanostruc-
3
4j
ture. However, to the best of our knowledge there is
no report on the use of this catalyst for the deprotection
of silyl ethers. The catalyst is made from a mixture con-
sisting of (3-mercaptopropyl) trimethoxysilane (MPTS),
tetramethoxysilane (TMOS), and cetyl trimethoxy
ammonium bromide, (CTAB), as a template or structure
directing agent (SDA). Extracted mecaptopropyl-
MCM-41 was oxidized to the corresponding sulfonic
acid derivative using HNO as the oxidant (Scheme
3
3
4j
1
).
The organic composition of the solid sulfonic acid was
quantitatively determined by thermogravimetric analy-
3
5
sis (TGA) and ion-exchange pH analysis. Typically a
loading of ca. 1.55 mmol/g was obtained.
In continuation of this work, herein we wish to report
a rapid and quite mild synthetic procedure for the
cleavage of various types of TBDMS ethers using a
trace amount (3.5 mol %) of solid sulfonic acid 1
Interestingly, our method can also be further extended
to the chemoselective deprotection of TBDMS ethers
in the presence of TBDPS ethers (Scheme 3). Such selec-
tivity can be applied in syntheses in which two protected
hydroxyl groups must be unmasked at different stages of
the synthesis.
(
Scheme 2).
The catalytic properties of the catalyst were first tested
in the deprotection of benzyl alcohol TBDMS ether.
In this regard, we found that a small amount of catalyst
1
ciently catalyzed the highly efficient deprotection of
(23 mg, 3.5 mol % of SO H groups) in methanol effi-
To demonstrate that the deprotection of silyl ethers cat-
alyzed by the catalyst 1 is really a heterogeneous pro-
cess, the deprotection of TBDMS-protected benzyl
alcohol was carried out in MeOH in which the catalyst
was filtered off at 55% conversion and the resulting clear
solution surveyed for additional conversion in the ab-
sence of the solid. GC analysis of the reaction mixture
after 4 h showed that no significant increase in the con-
version level occurs after removal of the catalyst, thus
indicating the solution does not contain any catalytically
active species that could have leached from the solid to
solution.
3
(MeO)4Si
CTAB (SDA), H2O, MeOH, NaOH
SS i Oi O22
SH
1) 12 h, rt, (2) 36 h, 95 o
(
C
(MeO)3Si
SH
(
1) 20% HNO3
SS i iOO 22
SO3H
(
2) conc. HNO3, 24 h, rt
1
1
.55 mmol SO3H.g-1
After having performed one reaction under the condi-
tions described in Table 1, the catalyst was recovered
by filtration, washed with an aliquot of fresh MeOH
and CH Cl , dried, and then reused for a consecutive
Scheme 1.
2
2
run under the same reaction conditions. Thus, after
the first run, which gave the corresponding benzyl alco-
hol in 94% yield, after recovery, the catalyst was sub-
jected to a second deprotection reaction from which it
also gave the benzyl alcohol in 94% yield; the average
chemical yield for seven consecutive runs was 92.5%,
OTBDMS SS i OO 22
R2
SO3H (3.5 mol%)
OH
R1
MeOH, 35 oC, 1.2-24 h
R1
R2
Scheme 2.

B. Karimi, D. Zareyee / Tetrahedron Letters 46 (2005) 4661–4665
4663
Table 1. Selective deprotection of TBDMS ethers to the corresponding alcohols using nanoporous solid silica sulfonic acid in methanol at 35 °C
a,b
Entry
Substrate
PhCH OTBDMS
4-i-PrC CH OTBDMS
4-NO CH OTBDMS
CH OTBDMS
OTBDMS
Product
PhCH OH
4-i-PrC
4-NO
Time (h)
Yield (%)
1
2
3
4
5
2
2
1.5
1.5
3
94
95
90
95
98
6
H
4
2
6
H
4
CH
CH
CH
OH
2
OH
OTBDMS
OH
2
C
6
H
4
2
2
C
6
H
4
2
PhCH
PhCH
2
CH
CH
2
2
PhCH
PhCH
2
CH
CH
2
2
1.3
1.5
2
2
2
2
6
OTBDMS
OH
1.2
93
OTBDMS
OH
7
Ph
Ph
11
90
Me
Me
OTBDMS
OH
8
9
12
87
OTBDMS
Me
OH
Me
1.2
4.5
98
94
OTBDMS
OH
10
11
12
13
14
15
16
OTBDMS
OH
3.2
3.2
2.5
9
90
95
90
88
OTBDMS
OH
OTBDMS
OH
OTBDMS
OH
c
60
Ph CH–OTBDMS
2
Ph
2
CH–OH
7
d
50
24
OTBDMS
OH
d
1
1
7
8
Me
OTBDMS
Me
OH
24
24
48
d,e
10
OTBDMS
OTBDMS
OH
OH
d,e
10
1
2
9
0
24
24
d,e
0
PhCH
2
CH CH
2
2
OTBDPS
PhCH
2
CH CH
2
2
OH
a
b
c
Yields refer to isolated pure products unless otherwise stated.
The ratio of TBDMS ether:catalyst 1:MeOH was 1:0.035:3 mL, respectively, and the reactions were performed 35 °C.
Upon increasing the reaction time the corresponding benzhydrylmethyl ether was formed as a by-product.
GC yield.
d
e
The ratio of TBDMS or TBDPS ether:catalyst 1:MeOH was 1:0.1:3 mL, respectively.
which clearly demonstrates the practical recyclability of
this catalyst (Fig. 1). This reusability demonstrates the
high stability and turnover of solid silica based sulfonic
acid 1 under the conditions employed.

4664
B. Karimi, D. Zareyee / Tetrahedron Letters 46 (2005) 4661–4665
Ph
Ph
OTBDPS
OTBDMS
Ph
Ph
OH 0%
>99%
Institute for Fundamental Research (IPM) Research
Council for partial support of this work.
Catalyst 1, (3.5 mol%)
MeOH, 1.5 h, 35 o
GC monitoring
C
OH
Supplementary data
OTBDMS
OTBDMS
OTBDMS
OH
0%
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2005.04.100.
Catalyst 1, (3.5 mol%)
MeOH, 1.5 h, 35 o
GC monitoring
C
Ph
Ph
OH
>99%
OH
References and notes
Catalyst 1, (3.5 mol%)
MeOH, 2 h, 35 C, 91%
1
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1
4
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