Deprotection of tetrahydropyranyl ethers with montmorillonite K-10 clay in methanol

Article abstract of DOI:10.1055/s-1999-2822

A variety of tetrahydropyranyl (THP) ethers are removed by Montmorillonite K-10 clay in methanol at room temperature to give alcohols. It has been shown that the THP ethers carrying epoxy, methoxymethoxy (MOMO), tertbutyldiphenylsiloxy (TBDP-SO-), acetoxy (AcO-) and benzoyloxy (BzO-) functionalities are stable under the conditions, while the ethers carrying ketal, tertbutyldimethylsioxy (TBSO-) and β,β,β-trichloroethylimidoxy [CCl₃C(=NH)O-] functionalities are unstable.

Full text of DOI:10.1055/s-1999-2822

LETTER
1247
Deprotection of Tetrahydropyranyl Ethers with Montmorillonite K-10 Clay in
Methanol
Takahiko Taniguchi, Kohei Kadota, Adel S. ElAzab, Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Fax +81-22-217-6845; E-mail: konol@mail.cc.tohoku.ac.jp
Received 23 April 1999
Rather surprisingly, since there has been no precedent us-
Abstract: A variety of tetrahydropyranyl (THP) ethers are removed
ing K-10 clay for the removal of the THP protecting group
by Montmorillonite K-10 clay in methanol at room temperature to
from THP ethers, though it was used as a catalyst for the
give alcohols. It has been shown that the THP ethers carrying ep-
oxy, methoxymethoxy (MOMO), tertbutyldiphenylsiloxy (TBDP-
formation of THP ethers,10,11 we examined the deprotec-
SO-), acetoxy (AcO-) and benzoyloxy (BzO-) functionalities are tion of a variety of THP ethers employing the above-men-
stable under the conditions, while the ethers carrying ketal, tertbu-
tioned K-10 clay-mediated methanolysis conditions to
tyldimethylsioxy (TBSO-) and b,b,b-trichloroethylimidoxy
extend its general synthetic utility. We wish to report here
the result indicating that the K-10 clay-mediated condi-
tions may be employed as a convenient method for the
deprotection of THP ethers.
[CCl3C(=NH)O-] functionalities are unstable.
Key words: deprotection, tetrahydropyranyl ether, Montmorillo-
nite K-10, methanolysis, epoxide
We first examined the methanolysis of a series of simple
primary, secondary, tertiary and aryl THP ethers. The re-
action was carried out by stirring the ethers in methanol
(5% w/v) with the same amount of K-10 clay at room tem-
perature. The reaction completed within 2 h to give the
corresponding alcohols in excellent yields, except the b-
naphthyl ether (Table 1: Entry 10 ). The b-naphthyl ether
was stable under prolonged stirring and even under reflux-
ing conditions (Table 1).
During our ongoing project, we encountered difficulty in
deprotection of the tetrahydropyranyl (THP) group from
the THP ethers carrying an epoxy functionality, such as 1,
to give the epoxy alcohols 2 without affection of the ep-
oxy functionality in their molecules. Among the examined
conditions, which were reported for the deprotection of
the THP protecting group, using diluted perchloric acid,1
p-toluenesulfonic acid-MeOH,2 aqueous acetic acid,3 py-
ridinium p-toluenesulfonate (PPTS)-MeOH,4 carbon tet-
rabromide-MeOH,5 and ceric ammonium nitrate (CAN)- Table 1 K-10 Clay-Mediated Deprotection of Simple THP Ethers
aqueous acetonitrile,6 only the CAN method6 allowed the
deprotection of 1a without touching the epoxy functional-
ity to give the alcohol7 2a in 74% yield. However, this
method could not be used for 1b having the 4-methoxy-
phenoxy (PMPO-) functionality as the PMP group was re-
moved concurrently under the conditions.8 We, therefore,
explored an alternative deprotecting method and found
that the methanolysis of the THP ethers 1 in the presence
of Montmorillonite K-10 clay allowed smooth removal of
the THP functionality to give the alcohols 2 in acceptable
yields without touching the epoxy functionality. Thus, on
stirring with the same weight of Montmorillonite K-10
clay in methanol at room temperature for 1 h, the THP
ethers 1a~c afforded the corresponding epoxy alcohols,9
2a in 77%, 2b in 76% and 2c in 73% yields, respectively
(Scheme 1).
Scheme 1
Synlett 1999, No. 8, 1247–1248 ISSN 0936-5214 © Thieme Stuttgart · New York

1248
T. Taniguchi et al.
LETTER
We next examined the same reaction using the THP ethers A typical procedure is as follows (Table 1: Entry 1): 4-
carrying an additional O- functional group in their mole- Benzyloxybutyl THP ether (500 mg, 1.9 mmol) in metha-
cules. Among the compounds examined under the same nol (10 ml) was stirred with Montmorillonite K-10 clay
conditions for the simple substrates above, the THP pro- (500 mg) at room temperature for 2 h. After filtration
tecting group was removed smoothly from the substrates through a Celite pad, the filtrate was evaporated under re-
carrying benzyloxy (Table 2: Entries 1 and 9), allyloxy duced pressure and the residue was chromatographed on
(Table 2: Entry 2), methoxymethoxy (MOMO) (Table 2: silica gel column (AcOEt-hexane, 1:2 v/v) to give 4-ben-
Entry 3), acetoxy (Table 2: Entry 6), benzyloxy (Table 2: zyloxybutyl alcohol (315 mg, 92%) as a colorless oil.
Entry 7), and tertbutyldiphenylsiloxy (TBDPSO) (Table
In summary, although there are some limitations to the
2: Entries 5 and 13), functional groups to give the corre-
methodology, the present K-10 clay-mediated metha-
sponding alcohols in good to excellent yields. On the oth-
nolytic deprotection of THP ethers may be practically use-
er
hands,
the
THP
ethers
carrying
ful as it may be carried out in an extremely easy way
employing neither difficult conditions nor expensive re-
agents.
tertbutyldimethylsiloxy12 (TBSO) (Table 2: Entries 4 and
12), b,b,b-trichloroethylimidoxy (Table 2: Entry 8), and
ketal11 (Table 2: Entries 10 and 11) functionalities were
unstable under these conditions. In particular, the ob-
served difference in stability between two silyloxy func-
tionalities (Table 2: Entries 4, 13 and 5, 14), as well as
between the methoxymethoxy functionality (Table 2: En-
try 3) and two ketal functionalities (Table 2: Entries 10
and 11), under the conditions was worthy of note (Table
2).
Acknowledgment
We are grateful for the Egyptian Associate Channel Sys-
tem Program Scholarship (to A. S. ElAzab).
References and Notes
(1) Stork, G.; Cohen, J. F. J. Am. Chem. Soc. 1974, 96, 5272.
(2) Corey, E. J.; Niwa, H.; Knolle, J. J. Am. Chem. Soc. 1978, 100,
1942.
(3) Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S.; Siret, P.;
Keck, G. E.; Gras, J. -L. J. Am. Chem. Soc. 1978, 100, 8031.
(4) Miyashita, M.; Yoshikoshi, A.; Grieco, P. A. J. Org. Chem.
1977, 42, 3772.
Table 2 K-10 Clay-Mediated Deprotection of Functionalized THP
Ethers
(5) Lee, A. S. -Y.; Su, F. -Y.; Liao, Y. -C. Tetrahedron Lett. 1999,
40, 1323.
(6) Dattagupta, A.; Singh, R.; Singh, V. K. Synlett 1996, 69.
See also: Ates, A.; Gautier, A.; Leroy, B. Plancher, J. M.
Quesnel, Y.; Markó, I. E. Tetrahedron Lett. 1999, 40, 1799.
(7) Katsuki, T.; Lee, A. W.; Ma, P.; Martin, V. S.; Masamune, S.;
Sharpless, K. B.; Tuddenham, D.; Walker, F. J. J. Org. Chem.
1982, 47, 1387.
(8) Fukuyama, T.; Laird, M.; Hotchkiss, L. M. Tetrahedron Lett.
1984, 25, 2295.
(9) Taniguchi, T; Ogasawara, K. Tetrahedron Lett. in press.
(10) Hoyer, S.; Laszlo, P.; Orlovic, M.; Polla, E. Synthesis 1986,
655.
(11) A pertinent review, see: Cornélis, A.; Laszlo, P. Synlett 1994,
155. See also: Gautier, E. C. L.; Graham, A. E.; Mckillop, A.;
Standen, S. P.; Taylor, R. J. K. Tetrahedron Lett. 1997, 38,
1881: Mohammadpoor-Baltork, I.; Nourozi, A. R. Synthesis
1999, 487: Heravi, M. M.; Ajami, D.; Mojtahedi, M. M.;
Ghassemzadeh, M. Tetrahedron Lett. 1999, 40, 561.
(12) Asakura, J.; Robins, M. J.; Asaka, Y.; Kim, T. H. J. Org.
Chem. 1996, 61, 9026.
Article Identifier:
1437-2096,E;1999,0,08,1247,1248,ftx,en;Y09899ST.pdf
Synlett 1999, No. 8, 1247–1248 ISSN 0936-5214 © Thieme Stuttgart · New York