Zinc triflate: A mild and efficient catalyst for deprotection of tetrahydropyranyl ethers

Article abstract of DOI:10.1134/S1070363213120384

Treatment of tetrahydropyranyl (THP) ethers with zinc triflate in methanol provides a simple and efficient process for deprotection of these ethers and the parent alcohols are obtained in excellent yields.

Full text of DOI:10.1134/S1070363213120384

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 12, pp. 2419–2422. © Pleiades Publishing, Ltd., 2013.
Zinc Triflate: A Mild and Efficient Catalyst for Deprotection
of Tetrahydropyranyl Ethers1
R. Srinivasulua, P. V. V Satyanarayanab, and K. Ravi Kumarc
a Chalapathi Institute of Engineering and Technology, Department of chemistry, Guntur, AP, India
e–mail: ramineni29@yahoo.com
b Department of Chemistry, Acharya Nagarjuna University, Guntur, AP, India
c RA Chem Pharma Limited, R&D Division, Prasanth Nagar, Hyderabad , AP, India
Received September 23, 2013
Abstract―Treatment of tetrahydropyranyl (THP) ethers with zinc triflate in methanol provides a simple and
efficient process for deprotection of these ethers and the parent alcohols are obtained in excellent yields.
DOI: 10.1134/S1070363213120384
for many synthetic conditions, many of these are
associated with several drawbacks, which include long
reaction time, reflux conditions, the use of catalysts
which may affect other functionalities present, severe
and acidic conditions, poor selectivity, formation of
polymeric byproducts of the dihydropyran, and iso-
merization. In addition, some of these catalysts require
a work-up of the reaction mixture. Thus, there is still a
need for mild selective methods for this purpose.
INTRODUCTION
Success of any protective group largely depends on
its stability to acidic or non-acidic reagents, and on the
fact that it can be easily installed and deprotected. The
tetrahydropyranyl (THP) group is widely used as a
hydroxyl protecting group, because it can easily be
introduced and is stable under a variety of reaction
conditions, including strongly basic conditions like
treatment with Grignard reagent, lithium alkyls,
alkylating, acylating reagents and reactions involving
oxidation and reduction by inorganic hydrides [1]. In
recent years, a number of different methods have been
reported for the deprotection of THP groups by using
protic acids, Lewis acids, ion exchange resins [2],
heteropolyacids, p-toluenesulfonic acid [3] and dif-
ferent catalysts like silica sulfuric acid [4], copper(II)
chloride [5], ceric ammonium nitrate [6], 3-carboxy-
pyridinium chlorochromate (CPCC) [7], decaborane
[8], poly(4-vinylpyridinium) p-toluenesulfonate [9],
cerium(III) chloride heptahydrate [10], N-bromosuccin-
imide (NBS) [11], 2,3-dichloro-5,6-dicyano-p-benzo-
quinone (DDQ) [12], PdCl2(CH3CN)2 [13], (K5CoW12O40·
3H2O) [14], tetrabutylammonium tribromide (TBAB)
[15], acetyl chloride [16], aluminum chloridehexa-
hydrate [17], indium triflate [18], bismuth triflate [19],
acetonyltriphenylphosphoniumbromide (ATPB) and
poly-p-styryldiphenylacetonylphosphonium bromide
[20], lithium bromide [21], zirconium tetrachloride
[22], MgBr2 [23], dimethylaluminum chloride [24],
NaHSO4–SiO2 [25]. Although these methods are suitable
Zinc(II) trifluoromethanesulfonate (zinc triflate)
has recently been shown to be a versatile reagent for
organic synthesis and it is used as a mild Lewis acid
catalyst for wide range of organic transformations [26–
28]. Zinc triflate is commercially available or it may be
prepared by reacting trifluoromethanesulfonic acid
with zinc carbonate in methanol [29]. Herein, we report
a simple and efficient zinc(II) triflate (10 mol %) catalyzed
deprotection of tetrahydropyranyl ethers (see scheme).
Zn(OTf)2
HO R
Methanol,
rt, 30-40 min
O
O
R
R = aryl, alkyl.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
400 MHz Varian FT-NMR spectrometer with tetra-
methylsilane (TMS) as the internal reference. The
solvent CDCl3 was used for NMR analysis. The mass
spectra were recorded on a Waters ZQ-4000 equipped
with ESI and API mass detector. The carbon, hydrogen
1
The text was submitted by the authors in English.
2419

2420
SRINIVASULU et al.
Deprotection of THP ethers by using zinc triflate in methanol at room temperaturea
Entry
Substrate
OTHP
Product
Time, min
30
Yield, %
96
a
OH
30
95
b
OTHP
OH
OHC
OHC
30
35
30
96
95
96
c
d
e
I
I
OH
I
OTHP
Cl
I
Cl
OTHP
OH
OTHP
OH
I
I
30
35
92
95
f
OTHP
OH
I
I
g
OTHP
OH
OH
O
O
35
90
h
OTHP
O2N
O2N
35
35
88
89
i
HN
Boc
OH
HN
Boc
OTHP
j
OTHP
OH
HN
Boc
HN
Boc
40
35
81
87
k
l
OTHP
OH
NC
NC
OTHP
OH
a The structures of the products were confirmed by direct comparison of their spectral data with published spectra.
and nitrogen (CHN) analysis was done on Perkin-
Elmer PE 2400 Series II analyzer. The thin layer
chromatography (TLC) was performed either using the
Merck precoated TLC plates or on ACME’s silica gel
with 13% calcium sulfate (CaSO4) as binder and the
components were visualized in iodine chamber or by
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

ZINC TRIFLATE: A MILD AND EFFICIENT CATALYST FOR DEPROTECTION
2421
UV exposure or by the potassium permanganate
(KMNO4) spray technique. Flash column chromato-
graphy was performed using Merck silica gel (100–
200 mesh). The chemicals and solvents were pur-
chased from commercial suppliers either from Aldrich,
Spectrochem, and Sisco research laboratories (SRL),
and they were used without purification prior to use.
The structures of generated alcohols were established
by direct comparison of their spectral (1H NMR,
400 MHz) data with those of the authentic alcohols.
tert-Butyl 3-hydroxypropylcarbamate (see table,
entry i). Colourless gummy compound. 1H NMR
(CDCl3), δ, ppm: 4.77 s (11H), 3.64–3.68 m (2H), 3.27–
3.31 m (2H), 3.01 t (J = 6Hz, 1H), 1.66–1.69 m (2H),
1.44 s (19H).
tert-Butyl 6-(tetrahydro-2H-pyran-2-yloxy)hexyl-
carbamate (see table, entry j). Colourless gummy
1
compound. H NMR (CDCl3), δ, ppm: 4.57–4.55 m
(1H), 4.51 s (11H), 3.89–3.87 m (1H), 3.76–3.70 m
(1H), 3.52–3.50 m (1H), 3.39–3.36 m (1H), 3.13–3.08
m (2H), 1.85–1.64 m (3H), 1.61–1.33 m (11H), 1.44 s
(19H); 13C NMR (CDCl3, 400 MHz), δ, ppm: 19.63,
25.40, 25.87, 26.55,28.35, 29.57, 29.94, 30.69, 40.45,
62.30, 67.40, 78.89, 98.80, 155.91; IR (DCM film, cm–1):
3355, 2936, 2865, 1702, 1523, 1365, 1251,1169,1033,
868. Calculated, %: C 63.75; H 10.37; N, 4.65; O
21.33. C16H31NO4. Found C 64.01; H 10.45; N, 4.72.
(LC-MS) m/z: 302.1 [M + H]+.
General procedure for deprotection reactions. A
solution of THP Ether (1.0 mmol) in methanol (10 mL)
was treated with Zn(OTf)2 (0.1 mmol) and stirred at
room temperature for 30–40 min. After the completion
of reaction (TLC analysis), the solvent was removed
under reduced pressure and the obtained residue was
treated with EtOAc (20 mL). The organic layer was
washed with water (10 mL), brine (10 mL), dried
(Na2SO4), and evaporated under reduced pressure to
give the crude product. It was purified by flash column
chromatography (100–200 mesh silica gel, EtOAc–
petroleum ether) to furnish the desired alcohols or
phenols in 81–96% yields.
tert-Butyl 6-hydroxyhexylcarbamate (see table,
1
entry j). Colourless gummy compound. H NMR
(CDCl3), δ, ppm: 4.49 s (1H), 3.62–3.65 m (2H), 3.10–
3.12 m (2H), 1.33–1.56 m (9H), 1.44 s (19H).
RESULT AND DISCUSSION
2-(4-Chloro-2-iodobenzyloxy)tetrahydro-2H-
pyran (see table, entry d). Light pale yellow gummy
compound. H NMR (CDCl3), δ, ppm: 7.82 s (11H),
A variety of THP ethers with different structures
were prepared according to standard procedures [30].
THP ethers were subjected to deprotection with 10 mol %
of Zn(OTf)2 in methanol at room temperature for 30–
40 min (see scheme). Under such conditions all the
THP groups investigated in our study were cleanly and
completely removed within a short time and the
corresponding alcohols and phenols were isolated in
good yields. The solvent plays an important role in the
deprotection reactions. It was found that methanol is
the best one among the solvents tested with THP ether
of 2-iodo phenol. Methanol gave the best results
compared to other solvents like ethanol, isopropyl
alcohol, acetone, acetonitrile, and THF.
1
7.41–7.33 m (2H), 4.77–4.75 m (1H) 4.71 d (J =
13.2 Hz, 1H), 4.44 d (J = 13.6 Hz, 1H), 3.93–3.87 m
(1H), 3.59-3.53 m (1H), 1.92–1.53 m (6H);13C NMR
(CDCl3, 400 MHz), δ, ppm: 19.26, 25.35, 30.42, 62.22,
72.23, 97.26, 98.42, 128.28, 129.20, 133.51, 138.25,
139.37. Calculated, %: C 40.88; H 4.00; Cl 10.05; I
35.99; O 9.08. C12H14ClIO2. Found, %: C 40.95; H
4.15. (LC-MS) m/z: 350.9 [M – H].
(4-Chloro-2-iodophenyl)methanol (see table, entry
d). Off-white solid; mp 114–116°C. 1H NMR (CDCl3),
δ, ppm: 7.87 (s, 1H), 7.48–7.44 m (2H), 5.52 t (J = 5.6
Hz, 1H), 4.38 d (J = 5.6 Hz, 2H). (LC-MS) m/z: 266.9
[M – H].
CONCLUSIONS
In conclusion, we have developed a simple,
inexpensive, and efficient protocol for deprotection of
THP ethers using Zn(OTf)2 at room temperature. The
reaction completed within 30–40 min. Experimental
simplicity, utilization of cheap, commercially available
catalyst and excellent yields are the main advantages
of the present procedure. Further, it was shown that
substrates such as Aldehyde, Boc, nitro, and methoxy
groups are also unaffected by the present reagent
system.
tert-Butyl 3-(tetrahydro-2H-pyran-2-yloxy)propyl-
carbamate (see table, entry i). Colourless gummy
compound. H NMR (CDCl3), δ, ppm: 4.92 s (11H),
4.57–4.56 m (1H), 3.85–3.78 m (2H), 3.51–3.43 m
(2H), 3.25–3.24 m (2H), 1.84–1.46 m (8H), 1.43 s
(19H); 13C NMR (CDCl3, 400 MHz), δ, ppm: 19.40,
25.34, 28.35, 29.57, 30.55, 38.61, 62.20, 65.70, 78.82,
98.81, 155.95. Calculated, %: C 60.21; H 9.72; N,
5.40; O 24.68. C13H25NO4. Found, %: C 60.44; H 9.98;
N 5.45.
1
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SRINIVASULU et al.
14. Habibi, M.H., Tangestaninejad, S., Baltork, I.M.,
ACKNOWLEDGMENTS
Mirkhani, V., and Yadollahi, B., Tetrahedron Lett.,
2001, vol. 42, pp. 2851–2853.
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16. Yeom, C.E., Shin, Y.J., and Kim, B.M., Bull. Korean.
Chem. Soc., 2007, vol. 28, pp. 103–107.
The authors are very grateful to the management of
Chalapathi Institute of Engineering and Technology,
Guntur, AP, India, for providing moral support in
carrying out this work.
17. Namboodiri, V.V. and Varma, R.S., Tetrahedron Lett.,
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