A simple, efficient and highly selective deprotection of t-butyldimethylsilyl (TBDMS) ethers using silica supported sodium hydrogen sulfate as a heterogeneous catalyst

Article abstract of DOI:10.1016/j.tetlet.2006.06.088

t-Butyldimethylsilyl (TBDMS) ethers have been efficiently and selectively deprotected using silica supported sodium hydrogen sulfate (NaHSO₄·SiO₂) as a heterogeneous catalyst at room temperature to regenerate the parent alcohols in high yields.

Full text of DOI:10.1016/j.tetlet.2006.06.088

Tetrahedron Letters 47 (2006) 5855–5857
A simple, efficient and highly selective deprotection of
t-butyldimethylsilyl (TBDMS) ethers using silica supported
I
sodium hydrogen sulfate as a heterogeneous catalyst
*
Biswanath Das, K. Ravinder Reddy and P. Thirupathi
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 24 April 2006; revised 5 June 2006; accepted 15 June 2006
Abstract—t-Butyldimethylsilyl (TBDMS) ethers have been efficiently and selectively deprotected using silica supported sodium
hydrogen sulfate (NaHSO
4 2
ÆSiO ) as a heterogeneous catalyst at room temperature to regenerate the parent alcohols in high yields.
ꢀ
2006 Elsevier Ltd. All rights reserved.
Protection of hydroxyl groups and subsequent deprotec-
tion are frequently applied in multistep transformations
and syntheses of complex organic molecules. The t-
for selective cleavage of TBDMS ethers over a wide
range of functional groups. Several TBDMS ethers were
selectively deprotected to the corresponding alcohols by
applying this catalyst at room temperature for 30 min
(Scheme 1, Table 1).
1
butyldimethylsilyl (TBDMS) group is widely used as a
hydroxyl protecting group as it can easily be introduced
2
and can withstand a variety of reaction conditions.
Cleavage of TBDMS ethers can be carried out using
TBAF but this reagent is costly and can cause side reac-
tions. As a result, various other methods including
The TBDMS ethers prepared from both primary and
secondary alcohols underwent deprotection smoothly
to the parent alcohols in high yields. TBDMS protected
long chain alcohols (Table 1, entries c and d) also pro-
duced the desilylated products in impressive yields.
The procedure is suitable for cleavage of TBDMS ethers
of unsaturated alcohols (entries f–i) as well as of chiral
alcohols (entries j–k). The protocol did not cause iso-
merization of double or triple bonds nor epimerization
of chiral centres. The structures of the products were
2
acidic, basic, oxidizing and reducing agents have been
3
introduced for this purpose. Although, these methods
are useful in organic synthesis, many of them suffer from
drawbacks such as the use of expensive catalysts, pro-
longed reaction times, complex experimental procedures
and disturbance to other functionalities. Thus, there is
still a need for an efficient method for selective deprotec-
tion of TBDMS ethers in the presence of other func-
tional groups.
1
established from their spectral ( H NMR and MS) data
and by direct comparison with authentic samples. The
optical rotations of the chiral alcohols were also verified.
In recent years, heterogeneous catalysts have gained
importance in several organic transformations due to
their interesting reactivity as well as for economic and
environmental reasons. In continuation of our work
with these catalysts we observed that silica supported so-
The chemoselectivity of the present procedure is inter-
esting. Phenolic TBDMS ethers remained unaffected
by the reagent (entries m and n). Such selectivity can
be applied in a synthesis in which two protected hydr-
oxyl groups (alcoholic and phenolic) require unmasking
4
dium hydrogen sulfate (NaHSO ÆSiO ) is highly efficient
4
2
NaHSO .SiO
4
2
Keywords: TBDMS ethers; NaHSO
tivity; Heterogeneous catalyst.
q
Part 92 in the series ‘Studies on novel synthetic methodologies’; IICT
Communication No. 060601.
4
ÆSiO
2
; Deprotection; Chemoselec-
CH Cl
2
2
R-OTBDMS
R-OH
9-94%
r. t., 30 min
8
*
Corresponding author. Tel./fax: +91 40 27160512; e-mail:
biswanathdas@yahoo.com
Scheme 1.
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.088

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B. Das et al. / Tetrahedron Letters 47 (2006) 5855–5857
a
4 2
Table 1. Selective cleavage of TBDMS ethers using NaHSO ÆSiO
Entry
Substrate
Product
Isolated yield (%)
93
OTBDMS
OH
a
OTBDMS
OH
b
92
c
C
16
18
H
33OTBDMS
37OTBDMS
C
C
16
H
H
33OH
37OH
92
92
d
C
H
18
OTBDMS
OH
e
94
f
90
93
91
OTBDMS
OTBDMS
OTBDMS
OH
g
h
OH
OH
OTBDMS
COOMe
OH
COOMe
i
j
89
90
OTBDMS
OH
k
l
OTBDMS
OH
OH
89
93
BocHN
BocHN
OTBDMS
N
Boc
N
Boc
OTBDMS
OTBDMS
m
n
—
91
OTBDMS
OH
TBDMSO
TBDMSO
OTHP
OTHP
o
p
—
—
COOMe
COOMe
MeO
AcO
O
MeO
AcO
O
COOMe
COOH
1
COOMe
COOH
q
r
—
—
a
All products were characterized from spectral ( H NMR, MS) data and by direct comparison with the parent alcohols.

B. Das et al. / Tetrahedron Letters 47 (2006) 5855–5857
5857
at different stages of the synthetic sequence. Under the
present experimental conditions an acid sensitive group
such as a THP (entry o) and a base sensitive group such
as an acetate (entry q) remained unchanged. Alkyl and
allyl ethers (entries p and r) and ester groups (entries i,
p and q) were not cleaved under these conditions. Addi-
tionally, the TBDMS ethers of N-Boc protected amino
alcohols underwent facile deprotection without interfer-
ing with the amine protecting group (entries k and l).
Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999.
. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972,
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9–71; (b) Vaino, A. R.; Szarek, W. A. J. Chem. Soc.,
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Chem. Commun. 1996, 2351–2352; (c) Maiti, G.; Roy, S. C.
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5
The catalyst NaHSO ÆSiO can easily be prepared from
Blacklock, T. Tetrahedron Lett. 2000, 41, 6021–6024; (g)
Bartoli, G.; Cupone, G.; Dalpozzo, R.; De Nino, A.;
Maiuolo, L.; Procopio, A.; Sambri, L.; Tagarelli, A.
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4
2
the readily available starting materials, NaHSO ÆSiO
4
2
and silica gel and is inexpensive and non-toxic. As
the reaction is heterogeneous in nature the catalyst can
6
easily be removed by simple filtration.
In conclusion, we have developed an exceedingly mild,
simple and efficient methodology for selective deprotec-
tion of TBDMS ethers using NaHSO ÆSiO as a hetero-
4
2
4. (a) Das, B.; Ramu, R.; Ravikanth, B.; Reddy, K. R.
Tetrahedron Lett. 2006, 47, 779–782; (b) Das, B.; Thiru-
pathi, P.; Reddy, V. S.; Rao, Y. K. J. Mol. Catal., A: Chem.
geneous catalyst. The process delivers very high yields of
the parent alcohols and is highly chemoselective.
2
006, 247, 233–239; (c) Das, B.; Majhi, A.; Banerjee, J.;
Chowdhury, N.; Holla, H.; Kishore, K. H.; Murthy, U. S.
N. Chem. Pharm. Bull. 2006, 54, 403–405.
. Breton, G. W. J. Org. Chem. 1997, 62, 8952–8954.
. Experimental procedure: A mixture of TBDMS ether
Acknowledgements
5
6
The authors thank UGC and CSIR, New Delhi, for
financial assistance.
(
1 mmol) and NaHSO ÆSiO (200 mg) in CH Cl2 (10 ml)
4 2 2
was stirred at room temperature for 30 min (TLC
indicated completion of the reaction). The catalyst was
removed by filtration and washed with EtOAc (2 · 5 ml).
The filtrate and washings were combined and the solvents
removed. The residue was subjected to column chromato-
graphy (silica gel, hexane–EtOAc) to yield the parent
alcohol.
References and notes
1
. (a) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart,
994; (b) Green, T. W.; Wuts, P. G. M. Protecting Groups in
1