A mild and efficient method for selective deprotection of tetrahydropyranyl ethers to alcohols

Full text of DOI:10.1021/jo9604898

6038
J . Org. Chem. 1996, 61, 6038-6039
Ta ble 1. Dep r otection of THP Eth er sa
A Mild a n d Efficien t Meth od for Selective
Dep r otection of Tetr a h yd r op yr a n yl Eth er s
to Alcoh ols†
Gourhari Maiti and Subhas Chandra Roy*
Department of Organic Chemistry,
Indian Association for the Cultivation of Science,
J adavpur, Calcutta - 700 032, India
Received March 11, 1996
The importance of selective introduction and removal
of protecting groups in organic synthesis is well estab-
lished. Tetrahydropyranylation of hydroxyl groups has
been recognized as a useful method for protection of
alcohols,1 because of its easy installation and general
stability to most nonacidic reagents. A method that
would effect the selective removal of tetrahydropyranyl
(THP) ethers in the presence of other sensitive functional
groups still remains as a goal. Generally the methods
used for the removal of THP ethers employ aqueous
reaction media acidified with mineral acids, or non-
aqueous media acidified with organic acids.2 There are
few examples which make use of aqueous or nonaqueous
neutral reaction conditions,3 and most of these methods
involve some costly and toxic reagents or formation of
considerable amounts of side products. We have estab-
lished that THP ethers can efficiently be deprotected by
treatment with excess of LiCl in H2O-DMSO at 90 °C.
This reaction produces the corresponding alcohols in
excellent yields, thus providing a mild and efficient
aqueous method for the deprotection of THP ethers which
does not require the use of acids or generate toxic waste
products.
A range of THP ethers were prepared from the corre-
sponding alcohols4 using the standard procedures [dihy-
dropyran (DHP) and pyridinium p-toluenesulfonate (PPTS)
in CH2Cl2] and subjected to deprotection using an excess
of LiCl and H2O in DMSO at 90 °C for 6 h. The results
are summarized in Table 1. All of the products were
purified by column chromatography, and the correspond-
ing alcohols were obtained in good yields. This method-
ology was very effective in removing THP ethers in the
presence of other sensitive functional groups such as
methylenedioxy ethers (entry 4, 6, 8, and 11), methoxy-
methyl ethers (C5H11CH2-OMOM remained unaffected),
benzyl ethers (entry 5), methyl ethers (entry 5, 9, and
14), and especially very sensitive aldehyde functionalities
† This paper is dedicated to Professor U.R. Ghatak on the occasion
his 65th birthday.
(1) (a) Reese, C. B. In Protecting Groups in Organic Chemistry;
McOmie, J . F. W., Ed.; Plenum Press: London, 1973; Chapter 3. (b)
Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; J ohn Wiley
and Sons, Inc.: New York, 1967; Vol. 1, pp 256. (c) Greene, T. W.;
Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; J ohn
Wiley and Sons, Inc.: New York, 1991; p 31.
(2) (a) Bauduin, G.; Bondon, D.; Pietrasanta, Y.; Pucci, B. Tetrahe-
dron 1978, 34, 3269. (b) Corey, E. J .; Niwa, H.; Knolle, J . J . Am. Chem.
Soc. 1978, 100, 1942. (c) Zimmermann, K. Synth. Commun. 1995, 25,
2959.
(3) (a) Caballero, G. M.; Gros, E. G. Synth. Commun. 1995, 25, 395
and references cited therein. (b) Nambiar, K. P.; Mitra, A. Tetrahedron
Lett. 1994, 35, 3033 and references cited therein. (c) Raina, S.; Singh,
V. K. Synth. Commun. 1995, 25, 2395. (d) Srikrishna, A.; Sattigeri,
J . A.; Viswajanani, R.; Yelamaggad, C. V. J . Org. Chem. 1995, 60, 2260.
(4) Some of the alcohols were prepared in our laboratory during the
total synthesis of lignans and related compounds; see (a) Adhikari, S.;
Roy, S. Tetrahedron Lett. 1992, 33, 6025. (b) Maiti, G.; Roy, S. C. J .
Chem. Soc., Perkin Trans. 1 1996, 403.
(entry 14). It is noteworthy that allylic or styrenyl double
bonds and propargylic triple bonds also remain un-
S0022-3263(96)00489-6 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 17, 1996 6039
affected under these reaction conditions. Interestingly,
the present reaction conditions, although somewhat
similar to the Krapcho method,5 except for lower tem-
peratures, did not affect the gem-dicarbethoxy groups
while deprotection of THP ethers occurred smoothly
(entry 13). The use of NaCl instead of LiCl did not effect
the deprotection at all, while it was found that H2O is
essential for the success of the reaction. DMSO was
found to be the solvent of choice to provide the maximum
yield of the product; use of HMPA or DMF as solvent
lowered the yield, while in benzene or THF the reaction
did not proceed at all.
Exp er im en ta l Section
Gen er a l P r oced u r e for Dep r otection of THP Eth er s
w ith LiCl a n d H2O in DMSO. A magnetically stirred mixture
of THP ether (2 mmol), LiCl (10 mmol), and H2O (20 mmol) in
DMSO (10 mL) was heated at 90 °C for 6 h under N2. The
reaction mixture was allowed to cool to rt, diluted with H2O (10
mL), and extracted with ether (25 mL × 3). The ether extract
was dried over anhydrous sodium sulfate. Evaporation of the
solvent followed by purification of the residue on a silica gel (10
g) column using a combination of ethyl acetate and light
petroleum (boiling range 60 °C to 80 °C) as eluent furnished
hydroxy compounds, which were identified by comparison (TLC,
IR, and 1H NMR spectra) with authentic compounds.
In conclusion, we have established a mild, simple, and
convenient method for the selective removal of the THP
protecting group using a combination of lithium chloride
and water in DMSO at 90 °C.
Ack n ow led gm en t. We thank CSIR, New Delhi for
financial support (Grant No. 01(1313)/94/ EMR-II). GM
thank UGC, New Delhi, for the award of a senior
research fellowship.
(5) (a) Krapcho, A. P. Synthesis 1982, 805. (b) Krapcho, A. P.
Synthesis 1982, 893.
J O9604898