Tetrahedron Letters
Cerium(IV) sulfate tetrahydrate: a catalytic and highly
chemoselective deprotection of THP, MOM, and BOM ethers
a,
⇑
a
a
b
Davir González-Calderón , Carlos A. González-González , Aydeé Fuentes-Benítez , Erick Cuevas-Yáñez ,
b
a,
⇑
David Corona-Becerril , Carlos González-Romero
a
Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM, Toluca-Atlacomulco km. 14.5, San Cayetano, Toluca, Estado de México 50200, Mexico
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Tetrahydropyranyl (THP), methoxymethyl (MOM), and benzyloxymethyl (BOM) phenyl/alkyl ethers were
efficiently cleaved to the corresponding parent hydroxyl compounds in good yields using catalytic
Received 27 July 2013
Revised 18 October 2013
Accepted 21 October 2013
Available online 31 October 2013
amounts of Ce(SO
4
)
2 2
Á4H O by microwave-assisted or conventional heating in methanol solution. Intra-
molecular and competitive experiments demonstrated the chemoselective deprotection of THP ethers
in the presence of triisopropylsilyl (TIPS) and tert-butyldiphenylsilyl (TBDPS) phenyl ethers.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Tetrahydropyranyl ethers
Methoxymethyl ethers
Benzyloxymethyl ethers
Alcohols
Cerium(IV) sulfate tetrahydrate
1
Tetrahydropyranyl (THP) ethers were one of the first generally
useful protecting groups for alcohols to be adopted and they are
decided to investigate the Ce(SO
pyranyl ether 1a in more detail.
4
)
2 2
Á4H O cleavage of tetrahydro-
2
still widely used today in multistep organic syntheses. The partic-
ular merits of THP group are its ease of introduction, the low cost of
dihydropyran, and its stability under a wide range of reaction con-
ditions. A drawback of THP group is the formation of an additional
stereocenter, therefore, methoxymethyl (MOM) and benzyloxym-
ethyl (BOM) ethers may be used instead THP of ethers.
Ce(SO ) 4H O
4 2 2
2
0 mol%
OTHP
OH
MeOH
MW or
1a
1
3
4
5
Several methods for THP, MOM, and BOM ether removal have
been reported. The most common methods involve acid hydroly-
sis; however, these methodologies are inappropriate in the case
of acid sensitive molecules. Thus, there is a need to develop new
alternatives to remove THP, MOM, and BOM ethers under mild
and preferably catalytic conditions. Recently, various inorganic
Table 1
Deprotection of THP ethers using 20 mol % Ce(SO
MW) or conventional heating (
4
)
2
Á4H
2
O in methanol by microwave
(
D)
Entry
Substrate
Alcohola
Yieldb,c (%)
MWd
De
6
salts have shown promise for THP ether cleavage, particularly,
7
cerium ammonium nitrate (CAN) are the unique cerium based
1
2
3
4
5
6
7
8
2a
3a
4a
5a
6a
7a
8a
9a
2
3
4
5
6
7
8
9
92
92
94
96
inorganic reagent reported for depyranylation, but their scope
and selectivity in the presence of silyl ethers have not been
explored.
During one of our current research programs, we observed that
menthol protected as THP ether 1a was cleaved within minutes
upon microwave heating in methanol containing cerium(IV) sul-
fate tetrahydrate. As a consequence of the above results, we
87
90
94
90
90
93
86
88
Trace
NR
Trace
NR
a
b
c
Confirmed by comparison with 1H NMR and 13C NMR with authentic sample.
Yields refer to chromatographically pure isolated compounds.
In some cases no reaction occurred (NR) or product yields were very low and ca.
⇑
90–95% of starting material was recovered.
d
1
6
30 °C, 20 min.
0 °C, 12 h.
e