A mild and efficient cleavage of tert-butyldimethylsilyl (TBS) and tetrahydropyranyl (THP) ethers using a catalytic amount of TBPA+ {radical dot} Sb Cl6-

Article abstract of DOI:10.1016/j.tetlet.2008.03.149

A mild and efficient method for the deprotection of the TBS and THP ethers is described. A wide variety of TBS ethers as well as THP ethers can be easily deprotected to the corresponding parent hydroxyl compounds by employing a catalytic amount of tris(4-bromophenyl)aminium hexachloroantimonate (TBPA^{+ {radical dot}} Sb Cl₆^-) in methanol at room temperature in good yield.

Full text of DOI:10.1016/j.tetlet.2008.03.149

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3634–3637
A mild and efficient cleavage of tert-butyldimethylsilyl (TBS)
and tetrahydropyranyl (THP) ethers using a catalytic amount
of TBPAþÅSbCl6
ꢀ
Yanfen Xu a, Shouchu Tang a, Junjie Han a, Xuegong She a,b,*, Xinfu Pan a
a Department of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, PR China
Received 6 March 2008; revised 27 March 2008; accepted 31 March 2008
Available online 8 April 2008
Abstract
A mild and efficient method for the deprotection of the TBS and THP ethers is described. A wide variety of TBS ethers as well as THP
ethers can be easily deprotected to the corresponding parent hydroxyl compounds by employing a catalytic amount of tris(4-bromophen-
yl)aminium hexachloroantimonate ðTBPAþÅSbCl6ꢀÞ in methanol at room temperature in good yield.
Ó 2008 Elsevier Ltd. All rights reserved.
The tert-butyldimethylsilyl (TBS)1a and tetrahydropyra-
Br
nyl (THP)1b ethers are frequently employed as protective
groups for hydroxyl functionalities in multi-step synthesis
due to their ease of preparation and stability under a wide
-
+
N .
Br
SbCl6
Br
variety of reaction conditions as well as their subsequent
ease of removal. In general, fluoride ion2 and aqueous
acids1a are the most popular reagents for the deprotection
of TBS ether. Recently, some reducing3 and oxidizing4
reagents have also been developed for the cleavage of
TBS ethers. However, these methods have drawbacks such
as the requirement for long reaction times, harsh reaction
conditions, and large amounts of reagents. Although
numerous synthetic methods5 have been developed for
the deprotection of TBS and THP ethers in recent years,
there is still a need for a catalytically efficient method under
Fig. 1. The structure of TBPAþÅSbCl6
.
ꢀ
of TBS and ꢀTHP ethers using a catalytic amount of
TBPAþÅSbCl6 in methanol at room temperature.
Initially, the TBS ether of dodecan-1-ol was chosen as a
model substrate to optimize the reaction conditions and the
results are summarized in Table 1. As shown in Table 1, thꢀe
best result was obtained using 5 mol % of TBPAþÅSbCl6
in methanol. When the amount of catalyst was reduced
to 1 mol %, a longer reaction time was required for comple-
tion of the reaction (entry 7).
mild reaction conditions. TBPAþÅSbCl6 (Fig. 1),6 nor-
ꢀ
mally used as a single electron transfer reagent and a rela-
tively stronger oxidant,7 to the best of our knowledge, has
not been used in the cleavage of any protecting groups.
Herein, we disclose a new mild method for the cleavage
With the optimized conditions8 in hand, varieties of TBS
ethers were synthesized and tested (Table 2). It has been
observed that in the case of the TBS ethers of primary alco-
hol (entries 1–4 and 6–8), the reactions were fast and the
*
Corresponding author. Tel.: +86 09318912582.
E-mail address: shexg@lzu.edu.cn (X. She).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.149

Y. Xu et al. / Tetrahedron Letters 49 (2008) 3634–3637
3635
Table 1
yields were high. We have also found that this method can
selectively remove TBS ethers in the presence of TBDPS
ethers9 and benzyl ethers (entries 2–6). When the TBS
ethers of secondary alcohols were tested (entries 5 and 9–
11), the reactions required longer times to obtain satisfac-
tory yields due to steric effects. However, there was no reac-
tion when TBS ethers of phenols were tested (entries 13–
16). This led us to explore the possibility of selective
removal of alkyl TBS ethers in the presence of aryl TBS
ethers. As expected, when entries 15 and 16 were tested,
the TBS ether of the alcohol was cleaved cleanly while
the TBS ether of phenol remained unaffected.
Deprotection of the TBS Ether of dodecan-1-ol
TBPA
OTBS
OH
10
solvent, rt
10
Entry
Equiv of TBPA+Å
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
7
a
0.05
0.05
0.10
0.10
0.10
0.05
0.01
CH2Cl2
CHCl3
MeCN
DMF
THF
MeOH
MeOH
18
12
12
8
6
0.5
1.5
71
86
94
<5
61
99
95
Isolated yields.
Table 2
Deprotection of various TBS ethers
OTBS
R2
TBPA
MeOH, rt
OH
R2
R1
R1
Entry
Substrate
Equiv of TBPA+Å
Time (h)
Product
Yielda (%)
OTBS
OH
10
1
2
3
0.05
0.05
0.05
0.5
0.5
0.5
99
99
93
10
OTBS
OH
BnO
BnO
OTBS
OH
TBDPSO
OTBDPS
TBDPSO
OTBDPS
4
5
0.05
0.05
1
2
99
97
OTBS
OH
OTBS
OH
OTBDPS
OTBDPS
6
0.05
1
99
TBDPSO
OTBS
TBDPSO
OH
OTBS
OH
7
8
0.10
0.05
0.5
1
74
96
OTBS
OH
OH
OH
9
0.05
0.05
2.5
87
83
OTBS
OTBS
OH
OH
10
2
OTBS
OH
11
12
0.05
0.10
1
3
99
70
OTBS
OH
(continued on next page)

3636
Y. Xu et al. / Tetrahedron Letters 49 (2008) 3634–3637
Table 2 (continued)
Entry
Substrate
Equiv of TBPA+Å
0.05
Time (h)
4
Product
Yielda (%)
NRb
OTBS
OH
13
14
O
O
OTBS
OH
0.05
0.05
0.05
0.05
4
1
1
1
NRb
OTBS
OTBS
OTBS
OH
15
16
17
97
TBSO
HO
OTBS
OTBS
OTBS
OH
92
TBSO
TBSO
45c
THPO
THPO
a
Isolated yields.
No reaction.
Butane-1,4-diol was obtained in 20% yield.
b
c
Table 3
Deprotection of various THP ethers
OH
OTHP
R2
5 mol% TBPA
R1
R2
Product
R1
MeOH, rt
Entry
Substrate
Time (h)
Yielda (%)
OTHP
OH
10
1
2
2
2
99
96
10
OTHP
OTHP
OH
OH
BnO
TBDPSO
BnO
TBDPSO
3
2.5
91
4
2.5
93
OTHP
OH
5
3
90b
H
H
H
H
H
H
THPO
HO
OTHP
OH
6
7
8
3
86
90
66
81
OTHP
OH
1.5
2
OTHP
OH
OTHP
OH
9
1
a
Isolated yields.
b
The reaction was conducted in mixed solvent (MeOH/CHCl3, 1/1, v/v).

Y. Xu et al. / Tetrahedron Letters 49 (2008) 3634–3637
3637
OP
R2
Acknowledgments
OH
R2
R1
R1
TBPA
We are grateful for the generous financial support by
NSFC (QT program, No. 20572037), NCET-05-0879,
and Gansu Science Foundation (3ZS051-A25-004).
1. P = TBS
2. P = THP
References and notes
TBPA
TBPA
OH
R2
OP
R2
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 4rd ed.; John Wiley & Sons: New York, 2007;
p 89; (b) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 4rd ed.; John Wiley & Sons: New York, 2007; p 59.
2. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190.
3. Corey, E. J.; Jones, G. B. J. Org. Chem. 1992, 57, 1028.
4. (a) Tanemura, K.; Suzuki, T.; Horaguchi, T. J. Chem. Soc., Perkin
Trans. 1 1992, 2997; (b) DuttaGupta, A.; Singh, R.; Singh, V. K.
Synlett 1996, 69; (c) Sabitha, G.; Syamala, M.; Yadav, J. S. Org. Lett.
1999, 1, 1701.
5. (a) Lee, A. S. Y.; Yeh, H. C.; Tsai, M. H. Tetrahedron Lett. 1995, 36,
6891; (b) Maiti, G.; Roy, S. C. Tetrahedron Lett. 1997, 38, 187; (c)
Jaume, F.; Carme, S.; Jaume, V. Tetrahedron Lett. 1998, 39, 327; (d)
Wang, M. J.; Li, C.; Yin, D. L.; Liang, X. T. Tetrahedron Lett. 2002,
43, 8727; (e) Crouch, R. D. Tetrahedron 2004, 60, 5833; (f) Khan, A.
T.; Islam, S.; Choudhury, L. H.; Ghosh, S. Tetrahedron Lett. 2004, 45,
9617.
R1
R1
ROP
ROH
Scheme 1. The plausible mechanism.
When entry 17 was tested, we found that the THP ether
was partially cleaved at the same time. So, we wondered
whether this reagent could be applied for the deprotection
of the THP ethers. Thus, several THP ethers were prepared
and subjected to these reaction conditions and the results
are summarized in Table 3. The reactions proceeded
smoothly and the corresponding alcohols were obtained
in high yields within 2–3 h. However, we noticed that the
THP ether of cholesterol could not be deprotected even
after long reaction times, due to the poor solubility in
methanol. But replacing methanol as the solvent with a
1:1 mixture of methanol and CHCl3 allowed the reaction
to proceed at a satisfactory rate and in high yield (entry
5). Interestingly, THP ether of phenol could be cleaved in
a short time (entry 9).
The plausible mechanism of the reaction is proposed
(Scheme 1). A single electron transfer process may be
involved.
In conclusion, we have developed a simple, inexpensive,
and mild procedure for the cleavage of TBS and THP
ethers which will have a wide scope in view of the tremen-
dous usefulness in organic synthesis.
6. Schmidt, W.; Steckhan, F. Chem. Ber. 1980, 113, 577.
7. (a) Dapperheld, S.; Steckhan, E.; Brinkhaus, K.-H. G.; Esch, T. Chem.
Ber. 1991, 124, 2557; (b) Bell, F. A.; Ledwith, A.; Sherrington, D. C. J.
Chem. Soc. 1969, 2719; (c) Jia, X. D.; Da, Y. X.; Yang, C. X.; Yang,
L.; Liu, Z. L. Tetrahedron Lett. 2008, 49, 1786.
8. General procedure: TBPAþÅSbCl6 (0.05 mmol) was added to
a
ꢀ
solution of TBS or THP ether (1 mmol) in methanol (5 mL). The
resulting mixture was stirred at room temperature and monitored by
TLC. After the reaction was complete, the mixture was diluted with
water (5 mL) and extracted with CH2Cl2 (10 mL ꢁ 3). The organic
extracts were collected, washed with brine and dried with anhydrous
Na2SO4. When the solvent was removed in vacuum, the residue was
purified by column chromatography on silica gel to afford the
corresponding alcohol or phenol.
9. (a) Crouch, R. D. Tetrahedron 2004, 60, 5833; (b) Nelson, T. D.;
Crouch, R. D. Synthesis 1996, 1031.