A mild and feasible deprotection of alcohol tetrahydropyranyl or methoxymethyl ethers catalyzed by Sc(OTf)3

Article abstract of DOI:10.1081/SCC-100104830

Tetrahydropyranyl or methoxymethyl ethers can be easily deprotected by treatment of a catalytic amount of scandium trifluoromethanesulfonate along with methanol or 1,3-propanediol, respectively, to afford the corresponding parent alcohols in high to excellent yields.

Full text of DOI:10.1081/SCC-100104830

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A MILD AND FEASIBLE DEPROTECTION OF ALCOHOL
TETRAHYDROPYRANYL OR METHOXYMETHYL ETHERS
CATALYZED BY Sc(OTf)3
Takeshi Oriyama a , Tsutomu Watahiki a , Yoshinobu Kobayashi a , Hiroyuki Hirano a
Takeshi Suzuki a
a Faculty of Science , Ibaraki University , Bunkyo, Mito, 310-8512, Japan
Published online: 09 Nov 2006.
&
To cite this article: Takeshi Oriyama , Tsutomu Watahiki , Yoshinobu Kobayashi , Hiroyuki Hirano & Takeshi Suzuki (2001)
A MILD AND FEASIBLE DEPROTECTION OF ALCOHOL TETRAHYDROPYRANYL OR METHOXYMETHYL ETHERS CATALYZED BY
Sc(OTf)3 , Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:15, 2305-2311, DOI: 10.1081/SCC-100104830
To link to this article: http://dx.doi.org/10.1081/SCC-100104830
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SYNTHETIC COMMUNICATIONS, 31(15), 2305–2311 (2001)
A MILD AND FEASIBLE DEPROTECTION
OF ALCOHOL TETRAHYDROPYRANYL
OR METHOXYMETHYL ETHERS
CATALYZED BY Sc(OTf)3
Takeshi Oriyama,* Tsutomu Watahiki,
Yoshinobu Kobayashi, Hiroyuki Hirano,
and Takeshi Suzuki
Faculty of Science, Ibaraki University, Bunkyo,
Mito, 310-8512, Japan
ABSTRACT
Tetrahydropyranyl or methoxymethyl ethers can be easily
deprotected by treatment of a catalytic amount of scandium
trifluoromethanesulfonate along with methanol or 1,3-propa-
nediol, respectively, to afford the corresponding parent alco-
hols in high to excellent yields.
Currently, much attention is being focused on novel, useful Sc(OTf)3-
catalyzed reactions in synthetic organic chemistry.1 In a previous paper, we
reported that in the presence of a catalytic amount (0.5 mol%) of Sc(OTf)3,
alkyl trialkylsilyl ethers undergo deprotection of silyl ethers efficiently and
chemoselectively.2 We demonstrated that alcoholic trialkylsilyl ethers have
been cleaved selectively in the presence of phenolic trialkylsilyl ethers.
*Corresponding author.
2305
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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ORIYAMA ET AL.
Herein we wish to report a highly efficient and convenient procedure
for the new deprotection of acetal-type protecting groups such as tetra-
hydropyranyl (THP)3 and methoxymethyl (MOM)4 ethers catalyzed by
Sc(OTf)3.
First, we examined the reaction of the THP ether of 3-phenylpropanol
with 0.5 mol% of Sc(OTf)3 combined with 5 equivalents of water in aceto-
nitrile. After 1 h at room temperature, usual work-up of the reaction mixture
afforded 3-phenylpropanol in 49% yield with concomitant recovery of the
THP ether (50%) (Table 1, Run 1).
Methanol was found to be a more effective additive in the deprotection
of the THP ether as depicted in Run 2. As expected, the yield or 3-phenyl-
propanol was improved by increasing the amount of CH3OH, and with 80
equivalents of CH3OH, > 95% deprotection was smoothly preformed
(Runs 5 and 6). Other solvents such as CH3NO2, THF, and CH2Cl2, need
longer reaction time as depicted in Runs 7–9.
After treatment of various alcoholic THP ethers under the above reac-
tion conditions (5 mol% Sc(OTf)3 and 80 equivalents of CH3OH in
CH3CN), the parent alcohols, including primary, secondary, and tertiary
aliphatic alcohols, are obtained in good to excellent yields as shown in
Table 2.5 In the case of benzylic THP ethers, the yield of alcohol is slightly
lower (Run 1). The reaction is similarly effective with phenolic THP ethers
Table 1. The Effect of Various Reaction Conditions
Run
x / mol%
y / equiv.
Solvent
Yielda %
1
2
3
4
5
6
7c
8c
9d
0.5
0.5
2
2
2
5
5
5
5
5b
5
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3NO2
THF
49
80
86
89
95
98
96
95
92
10
30
80
80
80
80
80
CH2Cl2
aIsolated yield of purified product; bH2O was used instead of MeOH; cReaction was
d
carried out for 6 h; Reaction was carried out for 8 h.

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Table 2. Sc(OTf)3-catalyzed Deprotection of Various THP
Ethersa
aThe reaction was carried out with 5 mol% of Sc(OTf )3 and
80 equiv. of MeOH for 1 h with aliphatic THP ethers or
0.5 mol% of Sc(OTf )3 and 10 equiv. of MeOH for 0.5 h
with phenolic THP ethers, unless otherwise noted; bIsolated
yield of purified product; cReaction was carried out for
d
10 min; Reaction was carried out for 2 h.

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ORIYAMA ET AL.
Table 3. Chemoselective Deprotection of THP Ethers
Run
PG
n
Yielda/%
1
2
3b
4c
Bn
Bz
4
4
4
6
95
97
74
90
t-BuPh2Si (TBDPS)
MOM
b
c
aIsolated yield of purified product; 0.5 mol% of Sc(OTf )3 was used; The reaction
was carried out for 8 h at 0ꢀC.
to provide the corresponding phenols in excellent yields. It is worth pointing
out that 0.5 mol% of Sc(OTf )3 and 10 equivalents of CH3OH are enough to
complete the deprotection of phenolic THP ethers. Additionally, THP
ethers that bear a benzyloxy or benzoyloxy group undergo chemoselective
deprotection to give the mono alcohols in excellent yields as depicted
in Runs 1 and 2 of Table 3. Chemoselectivity between the THP and
MOM ethers, which are both acetal-type protecting groups of the hydroxy
function, was excellent as shown in Run 4.
Next, we examined the deprotection of MOM ethers, which are widely
used as a typical acetal-type protecting group of the hydroxy function. We
found that 1,3-propanediol is a very effective alcohol as an additive in the case
of MOM ether removal. Various MOM ethers of primary, secondary, and
phenolic alcohols can be conveniently deprotected by 5 mol% of Sc(OTf )3
along with 2 equivalents of 1,3-propanediol in CH3CN at 50ꢀC or refluxing.
The representative and successful examples are summarized in Table 4.
Cleavage of the MOM ethers similarly occurred under identical reaction con-
ditions. In the case of phenolic MOM ethers, the reaction in refluxing THF
worked well, affording the parent alcohols in higher yields (Runs 6–10).
In conclusion, we have found that a catalytic amount of Sc(OTf )3
combined with an alcohol such as methanol or 1,3-propanediol cleaved
readily tetrahydropyranyl and methoxymethyl ethers under mild reaction
conditions to give the corresponding alcohols in high to excellent yields. The

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Table 4. Sc(OTf )3-catalyzed Deprotection of Various MOM
Ethersa
aThe reaction was carried out in refluxing CH3CN with aliphatic
MOM ethers or at 50ꢀC (oil bath temperature) in CH3CN with
phenolic MOM ethers. In parentheses, reaction was carried out
b
in refluxing THF; Isolated yield of purified product.
present method could be a new access for the convenient and selective
deprotection of tetrahydropyranyl and methoxymethyl ethers.
ACKNOWLEDGMENT
We deeply thank the Uehara Memorial Foundation for financial
support.

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ORIYAMA ET AL.
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scandium trifluoromethanesulfonate (7.5 mg, 0.015 mmol) was added
1-tetrahydropyranyloxy-3-phenylpropane (66.8 mg, 0.30 mmol) in
CH3CN (1.5 ml) and CH3OH (1.0 ml, 24.7 mmol) at room temperature
under argon atmosphere. The resultant mixture was stirred for 1 h at
room temperature and quenched with buffer (pH 7). The organic
materials were extracted with Et2O and dried over anhydrous sodium
sulfate. The solvent was evaporated and 3-phenylpropanol (40.7 mg,
98%) was isolated by thin-layer chromatography on silica gel
1
(ether:hexane ¼ 1:2). The product gave satisfactory H NMR and IR
spectra.
Received in Japan September 4, 2000

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