Deprotection of t-butyldimethylsilyl ethers promoted by cerium(IV) triflate

Article abstract of DOI:10.1016/S0040-4039(02)01254-6

t-Butyldimetylsilyl ethers are mildly cleft by catalytic amounts of cerium(IV) triflate. Dependence from water amount was observed.

Full text of DOI:10.1016/S0040-4039(02)01254-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5945–5947
Deprotection of t-butyldimethylsilyl ethers promoted by
cerium(IV) triflate
Giuseppe Bartoli,a Giovanna Cupone,b Renato Dalpozzo,b Antonio De Nino,b Loredana Maiuolo,b
Antonio Procopio,b,* Letizia Sambria and Antonio Tagarellib
aDipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, viale Risorgimanto 4, I-40136 Bologna, Italy
bDipartimento di Chimica, Universita` della Calabria, ponte Bucci cubo 15/c, I-87030 Arcavacata di Rende, Italy
Received 11 June 2002; accepted 27 June 2002
Abstract—t-Butyldimetylsilyl ethers are mildly cleft by catalytic amounts of cerium(IV) triflate. Dependence from water amount
was observed. © 2002 Elsevier Science Ltd. All rights reserved.
The chemical manipulation of complex polyfunctional
molecules often requires the sequential protection and
deprotection of the various functionalities. Silyl ethers
have attained a position of prominence in the area of
hydroxyl group protection due to their easy formation
and removal and their stability to a wide range of
reagents and reaction conditions.1 Among silyl ethers,
t-butyldimethylsilyl (TBS) is the most popular because
it can be easily installed in high yields and is robust to
a variety of reaction conditions.1 There are several
methods for the deprotection of TBS ethers, which
involve basic, reducing, oxidizing, high-temperature
conditions,2 which are the limitation and the usefulness
of this protecting group at the same time.
30 min, respectively.5 We used commercial products
and solvents without purification.
Dry solvents or dry salts6 in fact resulted in lower
yields, while low temperature slowed down the reaction
rate. Deprotections of many TBS ethers were per-
formed (Table 1). Aromatic ethers are cleft more slowly
than primary or secondary aliphatic and allyl ones. A
strong dependence from electronic and steric factors
was found in aromatic ethers. Electron withdrawing
and/or ortho substituents slower the reaction rate.
In order to establish the chemoselectivity of the
method, other octyl ethers (3–6) were allowed to cleave
in acetonitrile in the presence of catalytic amounts of
cerium(IV) triflate (Table 2).
Recently, stoichiometric amounts of cerium salts,
namely CeCl3/NaI mixture, have been proved useful in
promoting under neutral conditions deprotections
which need acid catalysts,3 among them, silyl ethers,
too have been deprotected.4
Table 1. Deprotection of TBS ethers to alcohols in aceto-
nitrile at room temperature
Entry
Ether
Time (h)]
Yield (%)
In conjunction with another ongoing project in our
laboratory, the synthesis of oligo- nucleotides and sac-
charides, we focused on the goal to deprotect hydroxyl
functionality with cerium salt in catalytic amounts.
1
2
3
4
5
6
7
8
9
1-TBSOC8H17
3-TBSOC8H17
AllylOTBS
PhCH2OTBS
PhOTBS
4-MeC6H4OTBS
2-MeC6H4OTBS
4-ClC6H4OTBS
2-ClC6H4OTBS
4-NO2C6H4OTBS
4-CHOC6H4OTBS
0.08
0.08
0.08
0.62
0.50
0.33
0.60
13
95
94
86
92
90
87
82
75
70
38a
57b
Commercial cerium(IV) triflate was found to be useful
in this endeavor. In fact, at room temperature, in
acetonitrile, a 10% molar amount of this salt is able to
deprotect t-butyldimethylsilyloxyoctane (1) and t-
butyldimethylsilyloxybenzene (2) in high yields in 5 and
17
52
52
10
11
a 52% of unreacted starting material was also recovered.
b 33% of unreacted starting material was also recovered.
* Corresponding author. Tel.: +39-0984-492043; fax: +39-0984-
492055; e-mail: procopio@unical.it
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01254-6

5946
G. Bartoli et al. / Tetrahedron Letters 43 (2002) 5945–5947
Table 2. Attempts of deprotection of protected octanol in
acetonitrile at room temperature with 10% of cerium(IV)
triflate
Ce(OTf)4 10%
CH3CN, 15 min
OTBS
21
OH
Product
Protecting group
Time [h]
Yield [%]
3
4
5
6
THP
TBDPS
Allyl
48
27
\96
\96
78
89
0
OTBS
Ce(OTf)4 10%
THF/H2O 4:1
6 h
22
PhCH2
0
OTBS
23
Ce(OTf)4 10%
CH3CN
Scheme 2.
TBSO(CH2)5OP
TBSO(CH2)5OH+PO(CH2)5OH+HO(CH2)5OH
Recently, the selective cleavage of multisilylated
nucleosides was reported to occur in THF/H2O 4:1
mixture as solvent.7 Therefore the cleavage of protected
alcohols 1–6 was performed in THF alone and in the
THF/H2O 4:1 mixture. Only TBSO-octane (1) was
cleaved in a reasonable reaction time (48 and 8 h,
respectively) in almost quantitative yields.
12 P=THP
7P=THP
11
16
13 P=TBDPS
14P=CH2=CHCH2
15 P=PhCH2
8 P=TBDPS
9 P=CH2=CHCH2
10 P=PhCH2
OP
OTBDPS OH
OH
Ce(OTf)4 10%
CH3CN
+
+
The same reactions were then made with diprotected
diols 7–10, 17–18 and in all cases protecting groups
different from TBS were unscathed, but reaction times
were considerably longer.
OP'
OH
OTBDPS OH
19
20
21
17 P=TBS, P'=TBDPS
18P=TBDPS, P'=TBS
Selective deprotection of alkyl TBS ether in the pres-
ence of aryl TBS ethers was recently attempted by
several research groups.8 Since we have in hand a
potential method to perform such interesting selective
deprotection, a competitive cleavage of TBSO-benzene
and TBSO-octane in the presence of 10% of cerium(IV)
triflate was attempted and after 2.5 h only octanol was
deprotected. Therefore, bis(t-butyldimethylsilyl)-3-(4-
hydroxyphenyl)propanol (22) was prepared and submit-
ted to deprotection in THF/H2O 4:1 at room
temperature in the presence of 10% amount of cerium
(IV) triflate (Scheme 2). After 6 h, the selective removal
of the aliphatic protecting group was observed.9 On the
other hand, in acetonitrile, full deprotection occurs and
unprotected 21 was recovered in 15 min.
Scheme 1.
Allyl and benzyl groups are unscathed under these
conditions, while tetrahydropyranyl (THP) and t-
butyldiphenylsilyl ethers are hardly removed.
Then we attempted chemoselective cleavage of 1,5-pen-
tandiol protected as TBS ether at one terminus and as
THP (7), TBDPS (8), allyl (9) and benzyl (10) at the
other one (Scheme 1). Only benzyl and allyl protecting
groups were not removed, the other ones being partially
or completely cleaved (Table 3, entries 1–4). In the
same manner, 3-(4-hydroxyphenyl)propanol protected
as TBDPS or TBS at the aromatic or aliphatic termi-
nus, respectively (17–18, Scheme 1), afforded the selec-
tive cleavage of the TBS ether both when it was bound
to the aliphatic or to the aromatic moiety (Table 3,
entries 5 and 6).
In conclusion, cerium(IV) triflate was demonstrated to
be a convenient deprotecting agent for TBS group. The
advantages of the method are: (i) the catalytic amounts
Table 3. Chemoselective deprotections of protected diols in acetonitrile or THF/H2O 4:1 at room temperature with 10% of
cerium(IV)triflate
Entry
Starting material
Solvent
Time (h)
Composition (%)
Overall yield (%)
1
2
3
4
5
6
7
8
9
7
8
9
10
17
18
7
8
9
10
17
18
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF/H2O 4:1
THF/H2O 4:1
THF/H2O 4:1
THF/H2O 4:1
THF/H2O 4:1
THF/H2O 4:1
2
1
7 (21), 11 (26), 12 (53)
11 (13), 13 (71), 16 (16)
14 (100)
15 (100)
20 (100)
19 (100)
12 (100)
13 (100)
14 (100)
\98
\98
91
\98
85
75
\98
80
90
83
75
70
0.5
2.5
0.5
0.5
2
24
18
2
10
11
12
15 (100)
20 (100)
19 (100)
8
7

G. Bartoli et al. / Tetrahedron Letters 43 (2002) 5945–5947
5947
requested, (ii) co-reagents unneeded, (iii) the extremely
simple experimental procedure, (purification, anhydi-
fication, inert or dry atmosphere are not requested), (iv)
very high deprotection yields, (v) high selectivity
towards TBS group, and (vi) selectivity towards alkyl
TBS group in the presence of aromatic ones. These
advantages are very useful in complex multistep synthe-
ses, which require the sequential protection and depro-
tection of the various functionalities.
gar, D. S. Tetrahedron Lett. 1999, 40, 7293–7294; (e)
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but longer reaction times are requested. 10% Molar
amount was the better compromise.
6. Berthet, J. C.; Lance, M.; Nierlich, M.; Ephritikhine, M.
Eur. J. Inorg. Chem. 2000, 1969–1973.
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