Caro's acid supported on silica gel. Part V: A mild and selective reagent for conversion of trimethyl silyl ethers to the corresponding hydroxy compounds

Article abstract of DOI:10.1080/10426500390220970

Mild and efficient method for deprotection of silyl ethers to alcohols is described using Caro's acid supported on silica gel. Reactions are carried out in dichloromethane at room temperature and their parent hydroxy compounds obtained in good to excellent yields. Using this procedure, tetrahydropyranyl ethers (THP) remain intact during desilylation reaction.

Full text of DOI:10.1080/10426500390220970

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Phosphorus, Sulfur, and Silicon and the Related
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Caro's Acid Supported on Silica Gel. Part V: A Mild and
Selective Reagent for Conversion of Trimethyl Silyl
ethers to the Corresponding Hydroxy Compounds
a
a
a
M. M. Lakouraj , M. Tajbakhsh & V. Khojasteh
a
University of Mazandaran , Babolsar, Iran
Published online: 23 Aug 2006.
To cite this article: M. M. Lakouraj , M. Tajbakhsh & V. Khojasteh (2003) Caro's Acid Supported on Silica Gel. Part V: A Mild
and Selective Reagent for Conversion of Trimethyl Silyl ethers to the Corresponding Hydroxy Compounds, Phosphorus, Sulfur,
and Silicon and the Related Elements, 178:9, 1865-1870, DOI: 10.1080/10426500390220970
To link to this article: http://dx.doi.org/10.1080/10426500390220970
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Phosphorus, Sulfur, and Silicon, 178:1865–1870, 2003
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390220970
CARO’S ACID SUPPORTED ON SILICA GEL.
PART V: A MILD AND SELECTIVE REAGENT FOR
CONVERSION OF TRIMETHYL SILYL ETHERS TO
THE CORRESPONDING HYDROXY COMPOUNDS
M. M. Lakouraj, M. Tajbakhsh, and V. Khojasteh
University of Mazandaran, Babolsar, Iran
(
Received January 14, 2003; accepted February 27, 2003)
Mild and efficient method for deprotection of silyl ethers to alcohols
is described using Caro’s acid supported on silica gel. Reactions are
carried out in dichloromethane at room temperature and their parent
hydroxy compounds obtained in good to excellent yields. Using this
procedure, tetrahydropyranyl ethers (THP) remain intact during desi-
lylation reaction.
Keywords: Caro’s acid; desilylation; tetrahydropyranyl ethers; tri-
methyl silyl ethers
Hydroxyl groups are present in a number of compounds of biological
and synthetic interest including nucleosides, carbohydrates, steroids,
and the side chain of some amino acids. During oxidation, acylation and
halogenation with phosphorus- or hydrogen halides, or deyhdration re-
1
action of these compounds a hydroxyl group must be protected. The
protective group must be selectively removed in good yield by readily
available preferably nontoxic reagents that do not attack the regener-
ated functional group.
The trimethyl silyl group has been used widely as a protective group
for alcohols. Their popularity is due in part to their ease of formation
and removal and their stability to a wide range of reagents and reaction
2
conditions.
There are several known methods for the deprotection of silyl
3
4
6
ethers. These include catalytic transfer hydrogenation using Pd,
5
reductive cleavage by DIBAL-H, ultrasonic cleavage in MeOH/CCl4,
DDQ, CAN, CAN-SiO2, I2, K2CO3/EtOH, LiCl/DMF/H2O/90 C,
7
8
9
10
11
◦
12
We thank the Mazandaran University Council for partial support of this work.
Address correspondence to M. M. Lakouraj, Department of Chemistry, School of Sci-
ence, University of Mazandaran, Babolsar 47415, Iran.
1
865

1
866
M. M. Lakouraj et al.
◦
13
◦
14
TASF/DMF,15 I2/MeOH,16
DMSO/H2O/90 C,
CBr4/MeOH/65 C,
17
18
TMSCl/MeCN/H2O, SC(OTF)3, bismuth bromide in wet acetonit-
rile, potassium fluoride, hydrogen fluoride, acetic anhydride and
1
9
20
21
2
2
23
24
iron(III), aqueous acetic acid, aqueous mineral acids, boron trifluo-
2
5
26
27
ride etherate, fluoroborate salts, NBS in DMSO, sodium azid in
2
8
29
30
DMF, sodium hydride in HMPA, P(MeNCH2CH2)3N, and TBAF/
THF, and have been described well in the literatures.
3
1
Protic as well as aqueous conditions are not safe for sensitive com-
pounds and suffer from aqueous work-up which makes difficult the iso-
lation of water soluble compounds. Some procedures that do not need
water for work-up suffer very seriously from long reaction time. Using
oxidizing agents for deprotection, the corresponding carbonyl groups
3
2
may be obtained due to oxidation of the parent alcohols. Although
Caro’s acid is a strong oxidizing agent, its utility in organic synthesis
has been limited by its insolubility in common organic solvents, and
its rapid deactivation on storage. This reagent is prepared in situ from
33
potassium persulfate and sulfuric acid. Caro’s acid has been used re-
cently for oxidation of organic compounds.34 We herein have examined
Caro’s acid supported on silica gel for selective deprotection of silyl
ethers.
We found that Caro’s acid supported on silica gel can be used to
deprotect aliphatic as well as aromatic silyl ethers to the corresponding
hydroxy compounds in good to excellent yields under mild conditions
(
Scheme 1).
SCHEME 1
The typical reaction consists of stirring the trimethyl silyl ethers
with equimolar quantity of the reagent in dichloromethane.
RESULTS AND DISCUSSION
As seen in Table I, a variety of TMS ethers were treated with this
oxidizing agent at ambient temperature. Aryl silyl ethers as well as
alkyl silyl ethers were easily converted to the corresponding parent
hydroxy compounds.
An advantage must be mentioned in that although Caro’s acid is
a powerful oxidant it never oxidizes the parent alcohol. At the above
conditions this reagent does not affect the THP ethers even after 24 h.

Caro’s Acid Supported on Silica Gel
1867
TABLE I Deprotection of Silyl Ethers Using Caro’s Acid Supported on
Silica Gel
Entry
Substrate
Producta
Time (min)b Yield (%)c
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
C6H5CH2OSiMe3
C6H5CH2OH
20
1.5
3
5
20
12
3
10
40
10
25
93
96
94
93
90
94
96
90
90
95
90
96
93
94
95
o-ClC6H4CH2OSiMe3
p-ClC6H4CH2OSiMe3
C6H5OSiMe3
2,4-(Me)2C6H3OSiMe3
PhCH CHCH2 OSiMe3
o-MeC6H4CH2OSiMe3
(C6H5)2CHOSiMe3
2,4-(Cl)2C6H3OSiMe3
C6H11OSiMe3
C6H5COCH(OSiMe3)C6H5
C6H5(CH2)2OSiMe3
ClCH2CH2OSiMe3
CH3(CH2)6CH2OSiMe3
o-ClC6H4CH2OH
p-ClC6H4CH2OH
C6H5OH
2,4-(Me)2C6H3OH
PhCH CHCH2 OH
o-MeC6H4CH2OH
(C6H5)2CHOH
2,4-(Cl)2C6H3OH
C6H11OH
1
1
1
1
1
1
C6H5COCHOHC6H5
C6H5(CH2)2OH
ClCH2CH2OH
2.5
10
7
8
CH3(CH2)6CH2OH
a
All products were fully characterized by spectroscopic methods.
The reaction was carried out in dichloromethane at room temperature.
Isolated yields.
b
c
In order to show the ability of this reagent in selective deprotection of
silyl ethers, equimolar amounts of trimethyl silyl ether and tetrahy-
dropyranyl ether were dissolved in CH2Cl2 and treated with Caro’s
acid on silica gel. As shown in Table II, after a short time trimethyl
silyl ethers were deprotected in excellent yields, while THP ethers were
unchanged.
TABLE II Competitive Deprotection of
Trimethyl Silyl Ethers to the Corresponding
Alcohols in the Presence of THP Ethers
Substrate
Time (min)
Yield (%)a
o-ClC6H4CH2OTMS
o-ClC6H4CH2OTHP
o-MeC6H4CH2OTMS
o-MeC6H4CH2OTHP
C6H5CH2OTMS
C6H5CH2OTHP
C6H5CH2CH2OTMS
C6H5CH2CH2OTHP
96
0
95
0
93
0
96
0
1
3
0
2
.5
2
.5
aIsolated yields.

1
868
M. M. Lakouraj et al.
TABLE III Comparison of Caro’s Acid Supported on Silica Gel with Some of
the Other Reagents in Regeneration of the Hydroxyl Group
Time
Substrate
Condition
CH2Cl2/r.t
(min)/Yield (%)
Reagent
Ref.
C6H5CH2OSiMe3
C6H5CH2OSiMe3
3/97
540/90
Caro’s acid/SiO2
O2/CO&Mn
salts/SiO2
—
36
n-Hexane/reflux
◦
C6H5OSiMe3
C6H5OSiMe3
n-C8H17OSiMe3
EtOH/H2O/75 C
600/100
5/93
1020/96
K2CO3
11
—
37
CH2Cl2/r.t
THF/H2O/r.t.
Caro’s acid/SiO2
Distannoxane/
Catalyst
CH3CH(CH2)5OSiMe3
|
◦
OSiMe3
PhCH2OSiMe3
PhOSiMe3
CH2Cl2/25 C
180/20
5/87
6/98
720/75
660/95
Ph3CBF4
38
◦
Benzene/80 C
[(NO3)3Ce]3H2|O6 39
CH3OH/r.t.
CH3CN/H2O, 80˚C/N2
Mont.K-10
CAN/BrO3
O2/CO&Mn
salts/SiO2
Zeofen
40
41
36
C5H9OSiMe3
PhCH CHCH2OSiMe3 n-Hexane/reflux
C6H5CH2OSiMe3 MW
20/96
42
To examine the effect of the silica gel on the deprotection of silyl
ethers, we carried out the desilylation reaction only in the presence of
silica gel. It has been found that the reaction does not occur and the
reaction mixture remained intact under this condition. In comparison
with some other reported methods, this method is remarkably conve-
nient, inexpensive, and works at ambient temperature. The advantage
of this reagent over other compounds is illustrated in Table III. This
method exhibits several preferred qualities for regeneration of parent
hydroxy compounds, for example: (1) easier work-up involving only fil-
tering, drying, and concentration. (2) higher selecivity and yields, and
(
3) simpler experimental manipulations and pure products. Summing
up, the Caro’s acid supported on silica gel is shown to be a mild, ef-
ficient, selective, and practical reagent for the deprotection of various
trimethyl silyl ethers to the corresponding alcohols in high to excellent
yields.
EXPERIMENTAL
All yields refer to the pure isolated products which were characterized
1
1
by IR, H-NMR, and comparison with authentic samples. H-NMR spec-
tra were recorded with a EM 360 A (60 MHz) spectrometer. IR spectra

Caro’s Acid Supported on Silica Gel
1869
were determined on a SP-1100, P-UV-Com instrument, and trimethyl
3
5
silyl ethers were prepared according to the reported method.
PREPARATION OF CARO’S ACID
To ice cooled 98% sulfuric acid (4.7 g) is added in small portions potas-
sium persulfate (4.5 g) with stirring; to this is added crushed ice (13 g)
◦
and water (4 g) while the temperature is kept below 15 C. Silica gel (5 g,
TLC grade, kieselgel 60 G, particle size 15 µm) is added in portions to
the mixture and stirred for 4 h in an ice-water bath. The mixture is
then filtered under suction and dried in a desiccator to give a white free
flowing powder.
GENERAL DEPROTECTION PROCEDURE
A suspension of trimethyl silyl ether (1 mmol) and Caro’s acid/silica gel
(
0.6 g, 1 mmol) in CH2Cl2 (4 ml) is prepared. The mixture is stirred
magnetically at room temperature for 1.5–40 min. Progress of the reac-
tion is monitored by TLC (hexane/ethyl acetate 3:1). After completion of
the reaction, the reaction mixture was filtered in a sinter glass funnel.
Evaporation of solvent on a rotary evaporator gave the desired hydroxy
compounds in high yields.
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