Phosphomolybdic acid supported on silica gel: An efficient, mild and reusable catalyst for the chemoselective hydrolysis of acetonides

Article abstract of DOI:10.1055/s-2005-872701

Carbohydrate acetonides were chemoselectively cleaved to the corresponding diols by using environmentally benign phosphomolybdic acid (H ₃PMo₁₂O₄₀) supported on silica gel (PMA-SiO₂) at ambient temperature in a

Full text of DOI:10.1055/s-2005-872701

LETTER
2461
Phosphomolybdic Acid Supported on Silica Gel: An Efficient, Mild and
Reusable Catalyst for the Chemoselective Hydrolysis of Acetonides
P
hosphom
.
olybdic
A
cid
S
Supported on
.
Silica
Gel Yadav,* S. Raghavendra, M. Satyanarayana, E. Balanarsaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(410)7160387; E-mail: yadavpub@iict.res.in
Received 26 May 2005
Crafts acylation of phenols,9 oxidation of alcohols10 and
regioselective opening of aziridines with nucleophiles
have been reported using HPAs.11
Abstract: Carbohydrate acetonides were chemoselectively cleaved
to the corresponding diols by using environmentally benign phos-
phomolybdic acid (H3PMo12O40) supported on silica gel (PMA–
SiO2) at ambient temperature in a short span of 5–7 minutes in ace-
tonitrile. Acid-labile protective groups such as THP, TBS, TBDPS,
MOM, OMe and PMB were found to be stable under the reaction
conditions.
Herein we wish to report phosphomolybdic acid support-
ed on silica gel (PMA/SiO2) as an efficient, mild and
reusable catalyst for the deprotection of the acetonides.
The hydrolysis was achieved by using 1 mol% of PMA/
SiO2 in acetonitrile at ambient temperature within a
course of 5–7 minutes (Scheme 1).
Key words: acetonides, phosphomolybdic acid, chemoselective
hydrolysis, silica gel
O
HO
HO
Protecting groups play a very important role in the field of
synthetic organic chemistry. Acetonide protection is one
of the most frequently used techniques in the multistep
synthesis of naturally occurring bioactive molecules for
the protection of 1,2-and 1,3-diols.1 Glucose diacetonide
and mannose diacetonides are most extensively used as
starting materials in Chiron approach.2 Chemoselective
deprotection of acetonides is an important transformation
in the synthetic strategies of biologically active natural
products, carbohydrates and nucleosides. Several mineral
acid reagents, such as aq HCl,3a aq HBr,3b aq AcOH,3c
0.8% H2SO4 in MeOH,3d Dowex-H+ in MeOH–H2O
(9:1),3e CF3COOH,3f CSA,3g p-TsOH3h and Lewis acid-
based reagents, FeCl3·6H2O/SiO2,4a CuCl2·2H2O in
O
O
O
OTs
OTs
PMA/SiO2, MeCN
r.t., 6 min
O
O
O
O
Scheme 1
The deprotection proceeded efficiently in high yield with
high chemoselectivity. From the blank experiments it was
confirmed that the acetonides are stable to silica gel in the
absence of PMA. The hydrolysis of acetonides took place
even with 1 mol% PMA. For the reusability of the catalyst
it has been supported on silica gel. The recovered catalyst
was reused for six times without any appreciable loss in
catalytic activity and presumably also yields of the
products.
EtOH,4b Zn(NO3)2·6H2O,4c CeCl3·7H2O/(COOH)2 and
4d
4e
BiCl3 have been reported to cleave this terminal
acetonide, but many of these methods suffer from dis-
advantages like strong acidic conditions, low yields, the
need to employ a stoichiometric amount of reagents and
long reaction times. Therefore, there is a need to develop
a mild and high yielding protocol for the chemoselective
hydrolysis of isopropylidene acetals.
Having established the optimum reaction conditions, the
deprotection of several representative acetonides was
performed to demonstrate the versatility and uniqueness
of the present reaction conditions. The acetonide group is
selectively cleaved leaving other functional groups
including olefins and ethers intact (Table 1). The method
is highly chemoselective allowing deprotection of ace-
tonides without effecting other hydroxyl protecting
groups such as PMB, THP, MOM, TBS, TBDPS, allyl,
propargyl, OBn, OAc, OMe, OTs groups. The systems
containing 1,3- and 1,2-acetonide protection have also
been investigated. Cleavage of 1,3-acetonides was ob-
served over 1,2-acetonides selectively. The results are
summarized in Table 2. The reaction proceeds smoothly
and rapidly in commercial grade acetonitrile with the ad-
dition of 40 mL of water, which promotes the hydrolysis
of acetonides.
Phosphomolybdic acid (PMA) belongs to the class of
heteropoly acids (HPA). Catalysis with HPAs is a field of
growing importance.5 HPAs are commercially available,
cheap and environmentally friendly catalysts. They ex-
hibit high activities and selectivities and allow cleaner
processing over conventional catalysts. HPAs have a very
strong Brønsted acidity. In fact, it is reported that HPA has
much higher activity than H2SO4, TsOH and BF3·OEt2.6
Synthetically a variety of methods have been developed
using HPAs as a catalyst which are being commercial-
ized.7 Fries rearrangement of phenyl acetate,8 Friedel–
SYNLETT 2005, No. 16, pp 2461–2464
0
4
.1
0
.2
0
0
5
In conclusion, we have developed a simple and efficient
protocol for the chemoselective hydrolysis of acetonides
Advanced online publication: 21.09.2005
DOI: 10.1055/s-2005-872701; Art ID: D14105ST
© Georg Thieme Verlag Stuttgart · New York

2462
J. S. Yadav et al.
LETTER
using 1 mol% of PMA/SiO2 as the catalyst. The advantage ecological consideration allows us to believe that this
of this method is the simplicity of operation, low cost of method represents a valuable alternative to the existing
the reagents, high yields of deprotected products and reus- reagents reported in literature.
ability of the catalyst. Moreover, its compatability with
sensitive functionalities such as MOM, THP, MPM, TBS,
TBDPS and double bonds with regard to economic and
Table 1 PMA/SiO2-Catalyzed Hydrolysis of Acetonides in Acetonitrile at Room Temparature12
Entry
a
Substrate
Producta
Reaction time (min)
6
Yield (%)b
94
HO
HO
O
O
O
O
O
O
O
O
O
O
b
c
5
6
92
92
HO
HO
O
O
O
O
O
O
OBn
O
OBn
HO
HO
O
O
O
OTs
OTs
O
O
O
O
d
e
7
6
90
95
O
O
HO
O
OH OBn
O
O
OBn
O
HO
HO
O
O
O
O
O
O
O
O
O
O
O
f
5
5
92
94
HO
HO
O
O
O
O
O
O
O
O
O
g
HO
HO
O
O
O
O
O
O
O
O
HO
HO
O
O
O
O
O
RO
O
RO
h
i
R = Ac
R = Bn
R = Ac
R = Bn
5
5
6
92
95
94
j
R = PMB
R = PMB
Synlett 2005, No. 16, 2461–2464 © Thieme Stuttgart · New York

LETTER
Phosphomolybdic Acid Supported on Silica Gel
2463
Table 1 PMA/SiO2-Catalyzed Hydrolysis of Acetonides in Acetonitrile at Room Temparature12 (continued)
Entry
Substrate
R = All
Producta
R = All
Reaction time (min)
Yield (%)b
k
l
5
5
5
7
5
7
90
90
93
94
92
90
R = Propargyl
R = MOM
R = TBDPS
R = Me
R = Propargyl
R = MOM
R = TBDPS
R = Me
m
n
o
p
R = TBS
R = TBS
HO
HO
O
O
O
OR
O
OR
O
O
O
O
q
r
R = Bn
R = Bn
6
4
5
5
4
5
5
5
5
93
91
95
90
94
90
89
92
90
R = MOM
R = THP
R = Propargyl
R = All
R = MOM
R = THP
s
t
R = Propargyl
R = All
u
v
w
x
y
R = TBS
R = TBS
R = TBDPS
R = Ac
R = TBDPS
R = Ac
R = PMB
R = PMB
a All products were characterized by 1H NMR spectroscopy and mass spectrometry.
b Yield of isolated product.
Table 2 PMA/SiO2-Catalyzed Hydrolysis of Acetonides in Acetonitrile at Room Temperature
Entry
i
Substrate
Producta
Reaction time (min)
4
Yield (%)b
90
O
O
O
O
O
HO
HO
O
O
O
O
ii
6
5
95
HO
O
HO
O
O
O
O
O
O
OMe
OMe
iii
92
O
O
OBn OH
OH OH OBn OH
a All products were characterized by 1H NMR spectroscopy and mass spectrometry.
b Yield of isolated product.
Synlett 2005, No. 16, 2461–2464 © Thieme Stuttgart · New York

2464
J. S. Yadav et al.
LETTER
(10) Firouzabadi, H.; Iranpoor, N.; Amani, K. Synthesis 2003,
408.
(11) Kishore Kumar, G. D.; Baskaran, S. Synlett 2004, 1719.
(12) Typical Experimental Procedure.
Acknowledgment
SR, MSN and EB thank CSIR, New Delhi for the award of research
fellowship.
(a) Preparation of PMA/SiO2 Catalyst.
PMA–SiO2 catalyst was prepared following the published
References
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(b) Preparation of Terminal Diols.
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To a solution of glucose diacetonide (260 mg, 1 mmol) in
MeCN (2 mL) were added the 1 mol% PMA/SiO2 (0.01
mmol, based on PMA) followed by 40 mL of H2O, and the
reaction mixture was stirred at ambient temperature for 5–7
min. After completion of the reaction as indicated by TLC,
the solvent was removed under reduced pressure and the
residue was dissolved in THF (2 mL) and filtered. The
filtrate was concentrated under reduced pressure and
purified by column chromatography (100–200 silica gel
mesh) using hexane and EtOAc as solvent system to afford
the pure diols. The filtered catalyst was reused without prior
drying.
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Spectral Data.
Entry b: [a]D +6 (c 1.76, CHCl3). 1H NMR (200 MHz,
CDCl3): d = 7.38 (s, 5 H), 5.75 (d, J = 3.8 Hz, 1 H), 4.64 (dd,
J1,2 = J2,3 = 3.7 Hz, 1 H), 4.54 (s, 2 H), 3.40–4.00 (m, 6 H),
2.00–2.40 (m, 1 H), 1.48 (s, 3 H), 1.29 (s, 3 H). MS–FAB:
m/z = 325.
Entry c: [a]D +2.8 (c 1, MeOH). 1H NMR (200 MHz,
CDCl3): d = 7.78 (d, J = 8.0 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2
H), 4.83 (d, J = 7.0 Hz, 1 H), 4.15 (d, J = 5.5 Hz, 1 H), 4.05
(d, J = 5.5 Hz, 1 H), 3.90 (d, J = 5.0 Hz, 1 H), 3.52–3.70 (m,
2 H), 2.60 (br s, 1 H), 2.50 (s, 3 H), 2.00 (br s, 1 H), 1.50 (s,
3 H), 1.32 (s, 3 H). MS–FAB: m/z = 389 [M+ + 1].
Entry d: [a]D –16.2 (c 0.4, CHCl3). 1H NMR (200 MHz,
CDCl3): d = 7.35–7.24 (m, 5 H), 6.98–6.82 (m, 1 H), 5.85 (d,
J = 15.6 Hz, 1 H), 4.69 (d, J = 11.1 Hz, 1 H), 4.46 (d,
J = 11.1 Hz, 1 H), 4.18 (q, J = 7.4 Hz, 2 H), 3.86–3.78 (m, 2
H), 3.50 (dd, J1,2 = 11.1, J2,3 = 5.9 Hz, 1 H), 3.35 (dd,
J1,2 = 11.1 Hz, J2,3 = 5.9 Hz, 1 H), 2.52 (t, J = 6.7 Hz, 2 H),
1.58–1.43 (m, 2 H), 1.28 (t, J = 7.4 Hz, 3 H). MS–FAB:
m/z = 331 [M+ + 23], 309 [M+ + 1].
Synlett 2005, No. 16, 2461–2464 © Thieme Stuttgart · New York