Chemoselective deprotection of trityl ethers using silica-supported sodium hydrogen sulfate

Article abstract of DOI:10.1016/j.tetlet.2004.07.075

A highly selective method for the cleavage of trityl ethers over a wide range of functional groups has been developed using silica-supported sodium hydrogen sulfate (NaHSO₄-SiO₂) as a heterogeneous catalyst. The conversion occurred at room temperature and the yields of the alcohols were found to be excellent.

Full text of DOI:10.1016/j.tetlet.2004.07.075

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6709–6711
Chemoselective deprotection of trityl ethers using
silica-supported sodium hydrogen sulfateI
Biswanath Das,* Gurram Mahender, Vooturi Sunil Kumar and Nikhil Chowdhury
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 7 June 2004; revised 7 July 2004; accepted 16 July 2004
Abstract—A highly selective method for the cleavage of trityl ethers over a wide range of functional groups has been developed using
silica-supported sodium hydrogen sulfate (NaHSO4–SiO2) as a heterogeneous catalyst. The conversion occurred at room tempera-
ture and the yields of the alcohols were found to be excellent.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Protection and deprotection of functional groups is very
important in organic transformations and syntheses.
Trityl (triphenylmethyl) ethers are widely used as pro-
tecting groups of primary alcohols, especially in carbo-
hydrate chemistry.1 Formation and removal of these
ethers are easy and they are stable under a variety of
reaction conditions. The trityl group also has a high
steric demand. However, the methods for selective cleav-
age of trityl ethers are limited. The reported methods use
different protic and Lewis acids such as mineral acids,2a
formic acid,2b acetic acid,2c trifluoroacetic acid,2d
ZnBr2,2e I2,2f BCl3,2g CeCl3,2h CBr4,2i and CAN2j for
this purpose. Many of these methods are associated with
several drawbacks including strongly acidic conditions,
corrosive reagents, necessity for reflux or cold tempera-
tures, incompatibility with other functional groups,
longer reaction times, and unsatisfactory yields. Several
methods also cleave glycosidic bonds. Additionally, var-
ious catalysts work under homogeneous conditions and
so the removal of these catalysts is a problem. Thus
there is still a need for mild and selective methods for
cleavage of trityl ethers using suitable catalysts.
ported sodium hydrogen sulfate (NaHSO4–SiO2) is an
efficient catalyst for deprotection of trityl ethers.
O
HO
NaHSO4.SiO2
O
O
TrO
O
CH2Cl2-MeOH(9:1)
O
2-2.5 h
r.t.
RO
91-100%
O
RO
R= H, Me, Bn, MOM, MEM, Allyl, Bz, Ts
Several trityl ethers were cleaved to produce the parent
alcohols in excellent yields (Table 1). The conversion oc-
curred at room temperature. In other reported methods
for cleavage of trityl ethers reflux or low temperature
was required.2 The present reaction took place smoothly
without requiring strongly acidic or basic conditions.
The glycoside moiety was completely intact and thus
the method is highly suitable for carbohydrate chemis-
try. Different types of sugars with various functionalities
were examined in order to determine the scope of the
reaction. Several other hydroxyl protecting groups such
as alkyl, Bn, MOM, MEM, Allyl, Ac, Bz, and Ts re-
mained unaffected. Trityl ethers derived from long-chain
alcohols were also easily cleaved. The method was also
found to be suitable for deprotection of trityl-protected
amines. The yields of the generated amines were
excellent.
In recent years, heterogeneous catalysts have gained
much importance due to enviro-economic factors. In
continuation of our work3 on the applications of hetero-
geneous catalysts for development of new synthetic
methodologies we have recently observed that silica-sup-
The catalyst NaHSO4–SiO2 can easily be prepared4
from the readily available NaHSO4 and silica gel (finer
than 200 mesh). It works under heterogeneous condi-
tions and can easily be handled and removed from the
Keywords: Trityl ether; Alcohol; NaHSO4–SiO2; Chemoselectivity.
I Part 43 in the series, ÔStudies on novel synthetic methodologiesÕ.
Corresponding author. Tel.: +91-40-7173874; fax: +91-40-7160512;
e-mail: biswanathdas@yahoo.com
*
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.075

6710
B. Das et al. / Tetrahedron Letters 45 (2004) 6709–6711
a
Table 1. Selective cleavage of trityl ethers using NaHSO4–SiO2
Entry
Substrate
Product
Time (h)
2
Yield
100
O
O
TrO
HO
O
O
a
O
O
O
HO
HO
HO
O
O
O
O
O
O
TrO
O
O
O
O
O
O
b
c
2
94
96
92
O
O
O
O
MeO
TrO
MeO
HO
2
O
O
BnO
HO
BnO
TrO
d
2.5
MOMO
TrO
MOMO
HO
O
O
O
O
O
O
O
O
e
f
2.5
2.5
91
96
O
O
MEMO
TrO
MEMO
HO
O
AllylO
HO
AllylO
TrO
O
O
O
O
O
O
O
O
g
2
2
97
95
O
O
O
O
BzO
TrO
BzO
HO
h
TsO
HO
TsO
TrO
HO
HO
O
O
O
O
i
j
2
2
100
O
O
HO
TrO
HO
HO
AcO
AcO
O
O
O
O
95
O
O
AcO
AcO
OTr
OH
k
l
2
97
95
OTr
OH
1.5
OTr
OH
m
n
2
93
94
HO
HO
3.5
17OTr
17OH
o
p
q
2.5
3.5
3.5
87
95
90
TrO
OTr
OTr
OH
OH
HO
H2N
H2N
TrNH
TrHN
OH
OH
a The structures of the products were established by direct comparison their spectral (1H NMR) data with those of the parent alcohols.

B. Das et al. / Tetrahedron Letters 45 (2004) 6709–6711
6711
Tsay, G. H.; Balakumar, A.; Hakimelahi, G. H. J. Org.
Chem. 2000, 65, 5077–5088.
reaction mixture. Moreover, the conversions occurred at
room temperature and therefore the experimental proce-
dure is simple.5 The structures of the generated alcohols
were established by direct comparison of their spectral
(1H NMR) data with that of the authentic alcohols.
3. (a) Ramesh, C.; Mahender, G.; Ravidranath, N.; Das, B.
Tetrahedron Lett. 2003, 44, 1465–1467; (b) Srinivas, K. V.
N. S.; Das, B. J. Org. Chem. 2003, 68, 1165–1167; (c)
Mahender, G.; Ramu, R.; Ramesh, C.; Das, B. Chem. Lett.
2003, 32, 734–735; (d) Ramesh, C.; Ravindranath, N.; Das,
B. J. Org. Chem. 2003, 68, 7101–7103; (e) Srinivas, K. V. N.
S.; Mahender, I.; Das, B. Synlett 2003, 2419–2421.
4. Breton, G. W. J. Org. Chem. 1997, 62, 8952–8954.
5. General procedure for detritylation: The trityl ether
(100mg) was dissolved in CH2Cl2–MeOH (9:1) (3mL).
The solution was stirred at room temperature for 5min. A
catalytic amount of NaHSO4–SiO2 was added. The mixture
was stirred and the reaction was monitored by TLC until
completion, when the mixture was filtered. The filtrate was
concentrated and the residue washed with n-hexane
(3 · 10mL). The residue was purified by column chroma-
tography using hexane–EtOAc (4:1) over silica gel to
generate the parent alcohol.
In conclusion, we have developed a novel, simple, inex-
pensive, and efficient protocol for deprotection of trityl
ethers using NaHSO4–SiO2 at room temperature. The
mild reaction conditions, experimental simplicity, utili-
zation of a cheap heterogeneous catalyst, high chemose-
lectivity and excellent yields are the main advantages of
the present procedure. We believe that the method will
find applications for selective cleavage of trityl ethers
in organic synthesis.
Acknowledgements
Spectral data of some representative trityl ethers are given
below. The deprotected products were characterized by
direct comparison (TLC, 1H NMR) with the parent
alcohols.
The authors thank CSIR, New Delhi for financial
assistance.
1a: 1H NMR (200MHz, CDCl3): d 7.44–7.12 (15H, m), 5.92
(1H, d, J = 4.0Hz), 4.45 (1H, d, J = 4.0Hz), 4.18 (2H, br s),
3.52 (1H, dd, J = 8.0, 6.0Hz), 3.41 (1H, dd, J = 8.0, 4.0Hz),
3.02 (1H, br s), 1.46 (3H, s), 1.27 (3H, s).
References and notes
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A.; Goodman, L. In Carbohydrate Chemistry and Biochem-
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2000, 329, 885–888; (j) Hwu, J. R.; Jain, M. L.; Tsai, F.-Y.;
1c: 1H NMR (200MHz, CDCl3): d 7.45–7.02 (20H, m), 5.82
(1H, d, J = 4.0Hz), 4.58–4.24 (4H, m), 3.92 (1H, d,
J = 4.0Hz), 3.48 (1H, dd, J = 8.0, 6.0Hz), 3.22 (1H, dd,
J = 8.0, 6.0Hz), 1.48 (3H, s), 1.25 (3H, s).
1h: 1H NMR (200MHz, CDCl3): d 7.60 (2H, d, J = 8.0Hz),
7.34–7.18 (15H, m), 7.14 (2H, d, J = 8.0Hz), 5.83 (1H, d,
J = 4.0Hz), 4.65 (2H, m), 4.12 (1H, m), 3.40 (1H, dd,
J = 8.0, 6.0Hz), 3.00 (1H, dd, J = 8.0Hz), 2.40 (3H, s), 1.42
(3H, s), 1.24 (3H, s).
1j: 1H NMR (200MHz, CDCl3): d 7.58–7.12 (15H, m), 5.88
(1H, d, J = 4.0Hz), 5.38 (1H, m), 5.18 (1H, m), 4.64 (1H,
dd, J = 10Hz, 4.0Hz), 4.42 (1H, d, J = 4.0Hz), 3.22–3.13
(2H, m), 2.02 (3H, s), 2.01 (3H, s), 1.48 (3H, s), 1.21 (3H, s).
1l: 1H NMR (200MHz, CDCl3): d 7.46–7.18 (20H, m), 3.38
(2H, t, J = 7.0Hz), 2.92 (2H, t, J = 7.0Hz).
1q: 1H NMR (200MHz, CDCl3): d 7.54–7.08 (30H, m), 3.08
(4H, dd, J = 7.0, 2.0Hz), 2.35 (4H, dd, J = 7.0, 2.0Hz).