A mild and efficient method for the chemoselective deprotection of acetonides with lanthanum(III) nitrate hexahydrate

Article abstract of DOI:10.1016/j.tetlet.2005.08.081

Acetonides are hydrolyzed selectively and efficiently with lanthanum(III) nitrate hexahydrate in acetonitrile. The method has good compatibility with other sensitive hydroxyl protecting groups such as trityl, TBDMS, THP, OAc, OBz and OBn.

Full text of DOI:10.1016/j.tetlet.2005.08.081

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7439–7441
A mild and efficient method for the chemoselective deprotection of
acetonides with lanthanum(III) nitrate hexahydrateI
S. Malla Reddy, Y. Venkat Reddy and Y. Venkateswarlu*
Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 14 July 2005; revised 8 August 2005; accepted 17 August 2005
Available online 9 September 2005
Abstract—Acetonides are hydrolyzed selectively and efficiently with lanthanum(III) nitrate hexahydrate in acetonitrile. The method
has good compatibility with other sensitive hydroxyl protecting groups such as trityl, TBDMS, THP, OAc, OBz and OBn.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
processes, there is merit in developing a truly catalytic
deprotection of acetonide groups using an inexpensive
and non-polluting reagent.
Protecting groups in organic synthesis, particularly in
multi-step synthesis of structurally complicated natural
products, are very important. However many syntheses
have failed because the protecting groups could not be
removed at the appropriate step.1 Acetonides are
commonly used to mask hydroxyl groups in polyhydr-
oxylated natural products, nucleosides and oligosaccha-
rides.2 As a consequence, many methods have been
developed for their formation and removal.3 Typically,
deprotection of acetals requires the use of protic or
Lewis acids.3,4 More recently alternative methods that
include the use of DDQ, aqueous DMSO, lithium
halides, silanes and insoluble acidic matrices have been
developed.5
In this letter (Scheme 1), we describe an efficient method
for the chemoselective deprotection of acetonide groups
using lanthanum(III) nitrate hexahydrate in acetonitrile
which gives the corresponding diols in high yields. This
method does not need expensive reagents or special care
to exclude moisture from the reaction medium. It is evi-
dent from Table 1, that a wide range of hydroxyl pro-
tecting groups such as trityl, TMS, THP, TBDMS, Bz,
Bn, prenyl, methyl and Ac groups, including acid labile
hydroxyl protecting groups, are left intact under the
reaction conditions. A primary acetonide group is
selectively hydrolyzed in the presence of a secondary
acetonide and other hydroxyl protecting groups. No
by-products were obtained.
However, many of these methods suffer from disadvan-
tages such as high acidity, long reaction times, unsatis-
factory yields, inconvenient handling and low chemo-
selectivity. In view of the current interest in catalytic
We first examined the reaction of 3-O-(tert-butyldi-
methylsilyl)-1,2:5,6-O-isopropylidene-a-D-glucofuranose
HO
HO
O
O
O
La(NO3)3. 6H2O/ CH3CN
reflux / 4 to 6 h
O
O
O
O
O
RO
RO
Scheme 1.
Keywords: Lanthanum nitrate hexahydrate; Chemoselective deprotection; Acetonides.
q IICT Communication No. 050805.
*
Corresponding author. Tel.: +91 40 27193167; fax: +91 40 27160512; e-mail: luchem@iict.res.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.081

7440
S. Malla Reddy et al. / Tetrahedron Letters 46 (2005) 7439–7441
Table 1. Chemoselective deprotection of acetonides with lanthanum(III) nitrate hexahydrate
Entry
1
Compound
Producta
Time (h)
5
Yieldb (%)
826
OTr
OTr
O
HO
HO
O
O
O
HO
HO
O
O
O
O
O
O
RO
RO
2
3
4
5
6
7
8
R = TMS
R = TBDMS
R = THP
R = Ac
R = Bz
R = Bn
R = TMS
6
6
5
5
5
5
5
818
967
947
947
907
967
908
R = TBDMS
R = THP
R = Ac
R = Bz
R = Bn
R = Me
R = Me
R =
9210a
H2C
H2C
9
5
R =
O
HO
O
O
887
O
O
O
O
HO
10
6
O
O
O
O
HO
OR
OR
O
O
HO
O
O
O
O
O
11
12
13
14
R = Me
R = Ac
R = Bn
R = Bz
R = Me
R = Ac
R = Bn
R = Bz
5
6
6
6
887
899
9210b
949
a All the products were characterized by 1H NMR, 13C NMR, IR and mass spectral analysis.
b Yields refer to isolated yields after column chromatography.
(Table 1, entry 3), with lanthanum(III) nitrate hexa-
hydrate in acetonitrile at room temperature for 24 h,
which gave the corresponding diol in 76% yield. In order
to improve the yield of the reaction, it was carried out at
reflux in acetonitrile for 4 h to give the corresponding
diol in 96% yield. This result encouraged us to carry
out the reaction in the presence of several different
hydroxyl protecting groups at reflux in acetonitrile, the
corresponding products were obtained in excellent yields
(Table 1).
heated under reflux for the appropriate time (Table 1).
After completion of the reaction as monitored by
TLC, the solvent was evaporated under reduced pres-
sure, water was added and the product was extracted
into ethyl acetate. The organic layer was dried over
anhydrous sodium sulfate and concentrated. The crude
product was purified over silica gel to yield the corre-
sponding diol (Scheme 1).
Acknowledgements
In conclusion, the present method for acetonide removal
has advantages in addition to an easy work-up procedure.
S.M.R. thanks the CSIR, India, for financial assistance.
2. General experimental procedure for the synthesis
of diols
References and notes
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hexahydrate (5 mol %) in acetonitrile (15 mL) was

S. Malla Reddy et al. / Tetrahedron Letters 46 (2005) 7439–7441
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10. (a) Spectral data for the product in entry 9 (Table 1):
25
Viscous liquid, ½aꢀD ꢁ27.8 (c 1.28, CHCl3): 1H NMR
(300 MHz, CDCl3): d 5.82 (1H, d, J = 3.9 Hz), 5.30 (1H, t,
J = 7 Hz), 4.49 (1H, d, J = 3.9 Hz), 4.00–4.13 (3H, m),
3.93 (2H, dd, J = 10, 7 Hz), 3.61–3.8 (2H, m), 3.04 (2H, br
s), 1.75 (3H, s), 1.69 (3H, s), 1.45 (3H, s) and 1.28 (3H, s);
EIMS m/z: 288 (M+); HRMS, obsd m/z 288.1564,
C14H24O6 requires m/z 288.1573; (b) Spectral data for
the product in entry 13 (Table 1): Viscous liquid,
25
1
½aꢀD ꢁ51.6 (c 2, CHCl3): H NMR (300 MHz, CDCl3): d
7.23–7.33 (5H, m), 4.82 (1H, d, J = 12.6Hz), 4.73–4.77
(2H, m), 4.54–4.60 (2H, m), 4.02 (1H, m), 3.82 (1H, dd,
J = 11.9, 3 Hz), 3.67 (2H, m), 1.52 (3H, s), 1.35 (3H, s);
EIMS m/z: 310 (M+); HRMS, obsd m/z 310.1424,
C16H22O6 requires m/z 310.1416.