A Simple and Facile Chemo- and Regioselective Deprotection of Acetonides Using Silica Supported Sodium Hydrogen Sulfate as a Heterogeneous Catalyst

Article abstract of DOI:10.1246/cl.2003.734

Silica supported sodium hydrogen sulfate (NaHSO₄·SiO ₂) has been found to be an efficient heterogeneous catalyst for chemo- and regioselective deprotection of acetonides at room temperature to produce the corresponding diols in excellent yields.

Full text of DOI:10.1246/cl.2003.734

734
Chemistry Letters Vol.32, No.8 (2003)
A Simple and Facile Chemo- and Regioselective Deprotection of Acetonides Using Silica
Supported Sodium Hydrogen Sulfate as a Heterogeneous Catalyst
G. Mahender, R. Ramu, C. Ramesh, and Biswanath Dasꢀ
Organic Chemistry Division-I,
Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received May 6, 2003; CL-030379)
a
Silica supported sodium hydrogen sulfate (NaHSO4ꢁSiO2)
Table 1. Deprotection of acetonides using NaHSO4ꢁSiO2
Entry Substrate (1)
has been found to be an efficient heterogeneous catalyst for che-
mo- and regioselective deprotection of acetonides at room tem-
perature to produce the corresponding diols in excellent yields.
Product (2) Time (h) Isolated
yield / %
O
OH
O
HO
Protection of functional groups and subsequent deprotec-
tion is highly useful in multistep transformations and synthesis
of complex organic molecules. Acetonides have frequently been
used for protection of 1,2-diols in carbohydrates and nucleo-
sides.2 The acetonides are subsequently cleaved to generate
the diols at an appropriate stage of a synthetic sequence. Several
protic acids (such as aq. HCl,3a aq. HBr,3b aq. HOAc,3c 0.8%
H2SO4 in MeOH,3d TFA,3e CSA3f and p-TsOH3g) are common-
ly used for this purpose. However, strong acids may affect other
functional groups and lower the selectivity of hydrolysis of ace-
tonides. The control of pH, temperature and reaction time is
thus necessary. A few Lewis acid based reagents (like
OR
OR
R=H
R=MOM
R=MEM
a
b
c
R=H
2
4
4
90
86
82
R=MOM
R=MEM
OH
O
O
HO
d
6
88
NHBoc
HO
NHBoc
O
O
HO
O
OR
O
OR
O
O
O
O
FeCl3ꢁ6H2O/SiO2,4a
CuCl2ꢁ2H2O,4b
Zn(NO3)2ꢁ6H2O,4c
e
f
g
R=H
R=Ac
R=H
R=Ac
R=Bn
2
4
4
95
92
88
4d
CeCl3ꢁ7H2O/(COOH)2 and BICl34e) have also been applied
for deprotection of acetonides. However, most of the methods
utilizing these reagents are associated with certain drawbacks
such as strong oxidizing and acidic conditions, long reaction
time, necessity of higher temperature and large amount of re-
agent, unsatisfactory yields and low selectivity. Additionally,
the majority of the protic and Lewis acids works under homo-
genous conditions and so it is some times difficult to handle
them as well as to remove from the reaction mixture.
Recently, we have observed that silica supported sodium
hydrogen sulfate (NaHSO4ꢁSiO2) is an efficient heterogeneous
catalyst for deprotection of acetonides. Several acetonides were
cleaved to the corresponding diols (Table 1) using this catalyst
at room temperature.
R=Bn
O
HO
O
HO
O
O
O
O
O
O
RO
RO
h
i
j
k
l
m
n
o
R=H
R=Ac
R=Bn
R=H
R=Ac
R=Bn
R=MOM
R=MEM
R=Bz
1
2
4
4
6
3
4
4
100
99
95
95
92
99
96
95
R=MOM
R=MEM
R=Bz
R=Ts
R=Ts
R=PMB
R=PMB
O
O
HO
HO
O
OH
MeO
p
3
92
O
O
NaHSO4.SiO2
O
OH
O
O
CH2Cl2-isopropanol(4:1)
r.t.
OH
O
O
O
MeO
RO
q
s
2
5
95
95
RO
OH
OH
O
92-100%
O
O
The method worked well with different acetonides of poly-
hydroxylated compounds. The conversion occurred with high
regioselectivity. The less hindered terminal acetonides of sugars
could only be cleaved. The partially protected sugars are appli-
cable as synthons for the preparation of various useful mole-
cules. The present method was also found to be associated with
high chemoselectivity. Several functional groups such as Me,
Bn, MOM, MEM, PMB ethers and Ac, Bz, and Ts esters re-
mained intact under the reaction conditions. N-Boc group was
also unaffected. The isomerisation of double bond and epimeri-
OH
____________________________________________________
aThe structure of all the products were settled from their spec-
tral (1H-NMR and MS data).
zation of a chiral centre were not observed. However with the
diols with -OTBS, -OTHP and –OTrityl the yields of the depro-
tected products were somewhat low (44-55%) and the order of
yields with these groups was observed as follows; -OTHP<
-OTBS< -OTrityl. The structures of the products were settled
from their spectral (1H NMR and MS) data.
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.8 (2003)
735
The catalyst, NaHSO4ꢁSiO2 can easily be prepared5 from
the readily available NaHSO4 and SiO2 (finer than 200 mesh)
and can properly be activated. Both the ingredients are inexpen-
sive and nonhazardous. The experimental procedure is simple
and the catalyst can easily be removed by filtration. From the
economic and ecological considerations the catalyst is highly
suitable to apply for cleavage of acetonides.
In conclusion, a novel, mild, and efficient method has been
developed for chemo- and regioselective deprotection of aceto-
nides using NaHSO4ꢁSiO2 as a heterogeneous catalyst. The op-
erational simplicity, excellent yields, availability of the inex-
pensive catalyst and high selectivity are the advantages of the
present protocol. We feel the method will find important appli-
cations in the selective cleavage of acetonides of polyhydroxy-
lated molecules.
(1977).
4
a) K. S. Kim, Y. H. Song, B. H. Lee, and C. S. Hahn, J.Org.
Chem., 51, 404 (1986). b) M. Iwata and H. Ohrui, Bull.
Chem.Soc.Jpn. , 54, 2837(1981). c) S. Vijayasaradhi, J.
Singh, and I. S. Aidhen, Synlett, 2000, 110. d) X. Xiao
and D. Bai, Synlett, 2001, 535.
5
6
G. W. Breton, J.Org.Chem. , 62, 8952 (1997).
Typical Experimental Procedure: To a solution of acetonide
(1 mmol) in CH2Cl2–isopropanol (4:1, 5 mL) NaHSO4ꢁSiO2
(100 mg) was added. The mixture was stirred at room tem-
perature and the reaction was monitored by TLC. After
completion, the mixture was filtered and the filtrate was
concentrated. The residue was subjected to column chroma-
tography over silica gel to obtain pure diol. The spectral da-
ta of some representative compounds are given below: 2c:
1H-NMR (200 MHz, CDCl3): d 5.80 (1H, m), 5.18-5.01
(2H, m), 4.97(1H, m), 4.64 (2H, s), 4.04 (1H, m), 3.78
(1H, m), 3.66-3.42 (5H, m), 3.38 (3H, s), 4.42-2.15 (2H,
m); FABMS: m=z 221 [M+1]þ. 2f: 1H-NMR (200 MHz,
CDCl3): d 6.15 (1H, s), 4.87(1H, dd, J ¼ 7:5, 6.0 Hz),
4.65 (1H, d, J ¼ 6:0 Hz), 4.04 (1H, m), 3.90 (1H, m), 3.78
(1H, d, J ¼ 11:5, 6.0 Hz), 3.62 (1H, m), 2.01 (3H, s), 1.34
The authors thank UGC and CSIR, New Delhi for financial
assistance.
References and Notes
1
Part 28 in the series, ‘‘Studies on Novel Synthetic Method-
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and B. Das, Adv.Synth.Catal. , (2003), submitted.
(3H, s), 1.23 (3H, s); FABMS: m=z 263 [M+1]þ. 2j: H-
1
2
a) T. W. Green, P. G. M. Wuts, ‘‘Protecting Groups in Or-
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York (1994).
NMR (200 MHz, CDCl3): d 7.38 (5H, m), 5.89 (1H, s),
4.78 (1H, d, J ¼ 7:5 Hz), 4.56-4.43 (2H, m), 4.05-3.97
(2H, m), 3.92 (1H, m), 3.78 (1H, dd, J ¼ 11:0, 5.5 Hz),
3.55 (1H, dd, J ¼ 11:0, 6.5 Hz); FABMS: m=z 311
1
3
a) G. W. J. Fleet and P. W. Smith, Tetrahedron Lett., 26,
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[M+1]þ. 2k: H-NMR (200 MHz, CDCl3): d 5.86 (1H, d,
J ¼ 2:0 Hz), 4.73-4.64 (2H, m), 4.52 (1H, d, J ¼ 2:0 Hz),
4.10 (1H, m), 4.03 (1H, dd, J ¼ 9:0, 2.0 Hz), 3.86-3.75
(2H, m), 3.72 (1H, m), 3.38 (3H, s), 1.42 (3H, s), 1.21
(3H, s); FABMS: m=z 265 [M+1]þ 2n: 1H-NMR
(200 MHz, CDCl3): d 7.80 (2H, d, J ¼ 8 Hz), 7.32 (2H, d,
J ¼ 8:0 Hz), 5.81 (1H, d, J ¼ 2:0 Hz), 4.86 (1H, d,
J ¼ 2:0 Hz), 4.42 (1H, m), 4.02 (1H, dd, J ¼ 9:5, 2.0 Hz),
3.78-3.64 (2H, m), 3.58 (1H, m); FABMS: m=z 359
[M+1]þ.
Published on the web (Advance View) July 21, 2003; DOI 10.1246/cl.2003.734