ether.deprotection.kmno4-alumina, biotransformation
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SYNTHETIC COMMUNICATIONS, 32(5), 771–779 (2002)
AN EASY AND FAST METHOD FOR
OXIDATIVE DEPROTECTION OF
TRIMETHYLSILYL ETHERS,
TETRAHYDROPYRANYL ETHERS, AND
ETHYLENE ACETALS WITH KMnO
4
SUPPORTED ON ALUMINA UNDER
SOLVENT-FREE CONDITIONS
A. R. Hajipour,
1,
*
S. E. Mallakpour,
1,
*
I. M. Baltork,
2
and H. Backnezhad
1
1
Pharmaceutical Research Laboratory, College of
Chemistry, Isfahan University of Technology,
Isfahan, 84156, IR, Iran
2
Department of Chemistry, Isfahan University,
Isfahan 81744, IR, Iran
ABSTRACT
A manipulatively simple and rapid method for oxidation
deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers
and deprotection of ethylene acetals to afford carbonyl com-
pounds under solvent-free conditions in the presence or
absence of alumina with potassium permanganate.
*Corresponding authors. E-mail: haji@cc.iut.ac.ir
771
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com
772
HAJIPOUR ET AL.
The protection and deprotection of the hydroxy functional groups can
play an essential role in synthetic strategy.
1
The transformation of alcohols
to the corresponding trimethylsilyl ethers is a very common way to protect
hydroxy groups.
1–3
In recent years a wide variety of methods have been
reported for oxidative cleavage of trimethylsilyl ethers to the corresponding
carbonyl compounds,
4–7
but some of the mentioned methods encounter
drawbacks such as the requirement for aqueous reaction conditions, use
of expensive reagents, long reaction times, low yields of the products and
tedious work-up. Therefore, introduction of new methods and inexpensive
reagents for such functional group transformations is still in demand.
The tetrahydropyranyl (THP) group is one of the most frequently used
groups to protect alcohols and phenols.
1,8
Owing to the outstanding
stability of tetrahydropyranyl ether under a variety of reaction conditions,
3,4-dihydro-2H-pyran is still a reagent of choice for protection of the
hydroxyl group in peptide, nucleotide and carbohydrate chemistry.
9
Since
direct transformation of tetrahydropyranyl ethers to their carbonyl com-
pounds is rare in the literature,
5,7,10–13
introduction of new methods is
desirable. Acetal formation is the most widely used protecting method for
aldehydes and ketones,
1
however, deprotection of acetals and ketals to the
corresponding carbonyl compound is a useful transformation in organic
synthesis.
13–18
Heterogeneous reactions that are facilitated by supported reagents
on various inorganic surfaces have recently attracted attention.
19
The
most advantage of these methods over conventional classical method
is that they show cleaner reactions, decreased reaction time and easier
work-up. In continuation of our ongoing program to develop environ-
mentally benign methods using solid supports,
20
we wish to report a
novel and e
>
cient method for the oxidative deprotection of trimethyl-
silyl and tetrahydropyranyl ethers to the corresponding carbonyl com-
pounds by with potassium permanganate (Scheme 1 and Table 1). This
oxidizing reagent is an inexpensive, water-soluble and stable oxidizing
reagent that is commercially available. This solvent is insoluble in non-
aqueous solvents; however, the requirement of aqueous conditions had to
be overcome.
Scheme 1.
OXIDATIVE DEPROTECTION
773
Table 1. Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl Ethers
with Supported KMnO
4
Time
(min)
Yield
(%)
a
Entry
Substrate
Product
1
PhCH
2
OTMS
PCHO
10
93
2
2-MeOC
6
H
4
CH
2
OTMS
2-MeOC
6
H
4
CHO
10
80
3
3-MeOC
6
H
4
CH
2
OTMS
3-MeOC
6
H
4
CHO
15
80
4
3-O
2
NC
6
H
4
CH
2
OTMS
3-O
2
NC
6
H
4
CHO
20
95
5
2,5-(MeO)
2
C
6
H
3
CH
2
OTMS
2,5-(Me)
2
C
6
H
3
CHO
10
75
6
PhCH(Me)OTMS
PhCOMe
15
99
7
4-ClC
6
H
4
CH(Me)OTMS
4-ClC
6
H
4
COMe
3
99
8
Ph
2
CHOTMS
Ph
2
CO
20
92
9
4-PhC
6
H
4
CH(Me)OTMS
4-PhC
6
H
4
COMe
15
90
10
a-TetralolTMS
a-Tetralone
10
95
11
PhCH
2
OTHP
PhCHO
5
95
12
2-MeOC
6
H
4
CH
2
OTHP
2-MeOC
6
H
4
CHO
20
75
13
3-MeOC
6
H
4
CH
2
OTHP
3-MeOC
6
H
4
CHO
20
82
14
4-MeOC
6
H
4
CH
2
OTHP
4-MeOC
6
H
4
CHO
10
90
15
3,4-(MeO)
2
C
6
H
3
CH
2
OTHP
3,4-(MeO)
2
C
6
H
3
CHO
10
90
16
2,5-(MeO)
2
C
6
H
3
CH
2
OTHP
2,5-(MeO)
2
C
6
H
3
CHO
15
88
17
PhCH(Me)OTHP
PhCOMe
10
90
18
4-ClC
6
H
4
CH(Me)OTHP
4-ClC
6
H
4
COMe
15
98
19
Ph
2
CHOTHP
Ph
2
CO
10
94
20
a-TetralolTHP
a-Tetralone
10
86
a
Yields based on the isolated products after column chromatography.
In order to evaluate the effect of alumina in this reaction we tried the
oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers with
potassium permanganate without using alumina. The rate of the reaction in
the absence of alumina is slower and the yield is lower (Table 2).
Potassium permanganate was also used to transform ethylene
acetals to the corresponding carbonyl compounds under solvent free
conditions in excellent yields (Scheme 2 and Table 3). Again the yield
Scheme 2.
774
HAJIPOUR ET AL.
Table 2. Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl Ethers
with KMnO
4
Time
(min)
Yield
(%)
a
Entry
Substrate
Product
1
PhCH
2
OTMS
PCHO
25
75
2
2-MeOC
6
H
4
CH
2
OTMS
2-MeOC
6
H
4
CHO
30
70
3
3-MeOC
6
H
4
CH
2
OTMS
3-MeOC
6
H
4
CHO
35
70
4
3-O
2
NC
6
H
4
CH
2
OTMS
3-O
2
NC
6
H
4
CHO
30
55
5
2,5-(MeO)
2
C
6
H
3
CH
2
OTMS
2,5-(Me)
2
C
6
H
3
CHO
35
70
6
PhCH(Me)OTMS
PhCOMe
25
70
7
4-ClC
6
H
4
CH(Me)OTMS
4-ClC
6
H
4
COMe
25
80
8
Ph
2
CHOTMS
Ph
2
CO
35
77
9
4-PhC
6
H
4
CH(Me)OTMS
4-PhC
6
H
4
COMe
25
80
10
a-TetralolTMS
a-Tetralone
25
75
11
PhCH
2
OTHP
PhCHO
40
45
12
2-MeOC
6
H
4
CH
2
OTHP
2-MeOC
6
H
4
CHO
35
60
13
3-MeOC
6
H
4
CH
2
OTHP
3-MeOC
6
H
4
CHO
30
55
14
4-MeOC
6
H
4
CH
2
OTHP
4-MeOC
6
H
4
CHO
30
60
15
3,4-(MeO)
2
C
6
H
3
CH
2
OTHP
3,4-(MeO)
2
C
6
H
3
CHO
25
65
16
2,5-(MeO)
2
C
6
H
3
CH
2
OTHP
2,5-(MeO)
2
C
6
H
3
CHO
30
60
17
PhCH(Me)OTHP
PhCOMe
35
55
18
4-ClC
6
H
4
CH(Me)OTHP
4-ClC
6
H
4
COMe
30
75
19
Ph
2
CHOTHP
Ph
2
CO
30
69
20
a-TetralolTHP
a-Tetralone
35
72
a
Yields based on the isolated products after column chromatography.
of transformation of ethylene acetals to the corresponding carbonyl
compounds with potassium permanganate without using alumina is lower
and also the rate is slower (Table 4). The cinnamaldehyde acetal as an
allylic carbonyl compound derivative was not converted to its corres-
ponding aldehyde properly with this reagent, and many by-products
were obtained. Interestingly, overoxidation of the products was not
observed by this method. In comparison to benzylic trimethylsilyl
ethers, benzylic tetrahydropyranyl ethers and benzylic ethylene acetals, oxi-
dation deprotection of aliphatic trimethylsilyl ethers and aliphatic
tetrahydropyranyl ethers or deprotection of aliphatic ethylene acetals
with this reagent does not occur at all. Therefore this reagent is not
suitable for oxidation deprotection of aliphatic trimethylsilyl ethers and
aliphatic tetrahydropyranyl ethers or deprotection of aliphatic ethylene
acetals.
OXIDATIVE DEPROTECTION
775
Table 3. Deprotection of Ethylene Acetals with Supported KMnO
4
Time
(min)
Yield
(%)
b
Entry
Substrate
Product
1
Acetophenoneethylene acetal
Acetophenone
5
98
2
2-Methoxybenzaldehyde-
ethylene acetal
2-Methoxybenzaldehyde
15
92
3
2-Nitrobenzaldehydeethylene
acetal
2-Nitrobenzaldehyde
15
75
4
2-Chloroacetophenone-
ethylene acetal
2-Chloroacetophenone
15
85
5
a-Tetraloneethylene acetal
a-Tetralone
10
90
6
4-Phenylacetophenone-
ethylene acetal
4-Phenylacetophenone
15
85
a
Yields based on the isolated products after purification with column
chromatography.
Table 4. Deprotection of Ethylene Acetals with KMnO
4
Time
(min)
Yield
(%)
a
Entry
Substrate
Product
1
Acetophenoneethylene acetal
Acetophenone
25
68
2
2-Methoxybenzaldehyde-
ethylene acetal
2-Methoxybenzaldehyde
35
70
3
2-Nitrobenzaldehydeethylene
acetal
2-Nitrobenzaldehyde
35
55
4
2-Chloroacetophenone-
ethylene acetal
2-Chloroacetophenone
40
55
5
a-Tetraloneethylene acetal
a-Tetralone
40
20
6
4-Phenylacetophenoneethylene
acetal
4-Phenylacetophenone
35
50
a
Yields based on the isolated products after purification with column
chromatography.
In summary, in this study we introduced a new and cheap method-
ology for the oxidative deprotection of trimethylsilyl and tetrahydropyranyl
ethers and deprotection of ethylene acetals to the corresponding carbonyl
compounds in high yields under solvent-free conditions. The low price of
the reagent, easy work-up, mild reaction conditions, and high yield of the
products, make this method a novel and useful method for the oxidative
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