Mild, efficient, and selective cleavage of trityl ethers with antimony trichloride

Article abstract of DOI:10.1080/00397910500522041

Selective detritylation is quite crucial in synthetic chemistry. A mild and efficient procedure for selective hydrolysis of trityl ethers in the presence of other frequently used hydroxy protecting groups: TBDPS, Bz, Bn, Ac and Ts with antimony trichloride was described and 5′-trityl uridine was detritylated smoothly too. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500522041

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Mild, Efficient, and Selective Cleavage of
Trityl Ethers with Antimony Trichloride
Qinpei Wu a , Yuan Wang a , Wei Chen a & Hua Liu a
a Department of Applied Chemistry, Beijing Institute of Technology, Beijing,
China
Version of record first published: 16 Aug 2006.
To cite this article: Qinpei Wu , Yuan Wang , Wei Chen & Hua Liu (2006): Mild, Efficient, and Selective
Cleavage of Trityl Ethers with Antimony Trichloride, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 36:10, 1361-1366
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Synthetic Communicationsw, 36: 1361–1366, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500522041
Mild, Efficient, and Selective Cleavage of
Trityl Ethers with Antimony Trichloride
Qinpei Wu, Yuan Wang, Wei Chen, and Hua Liu
Department of Applied Chemistry, Beijing Institute of Technology,
Beijing, China
Abstract: Selective detritylation is quite crucial in synthetic chemistry. A mild and
efficient procedure for selective hydrolysis of trityl ethers in the presence of other
frequently used hydroxy protecting groups: TBDPS, Bz, Bn, Ac and Ts with
antimony trichloride was described and 50-trityl uridine was detritylated smoothly too.
Keywords: Hydrolysis, trityl ether, antimony, protecting groups, catalysis, Lewis acid
The triphenylmethyl (trityl) group has widely been used as protecting groups
for alcohols in synthetic chemistry, especially in the fields of carbohydrates,
nucleosides, and nucleotides, owing to its easy installation and stability in
mild acidic and basic reaction conditions.[1] In fact, both selective installation
and selective deprotection strategies are essential and critical objectives with
multifunctional groups in particular.[1] The reagents employed to cleave trityl
groups include protic acids such as formic acid,[2] 80% acetic acid,[3] trifluoro-
acetic acid (TFA),[4] and NaHSO4–SiO2.[5] However, these acid conditions
often give rise to limited usage of trityl protecting groups because most
protecting groups and some substrates are sensitive to acids. Alternative
reagents were developed for this purpose, for example, ZnBr2,[6]
I2–MeOH,[7] BCl3,[8] CeCl3–NaI,[9] CBr4,[10] cerium ammonium nitrate
(CAN),[11] Ce(TfO)4,[12] BiCl3,[13] Yb(TfO)3,[14] triethylsilyl trifluoromethan-
sulfonate (TESOTf)–Et3SiH–AcOH,[15] and Li–naphthalene.[16] Some
Received in China February 1, 2006
Address correspondence to Qinpei Wu, Department of Applied Chemistry, Beijing
Institute of Technology, Beijing 100081, China. Fax: þ8610 6891 3293; E-mail:
qpwu@bit.edu.cn
1361

1362
Q. Wu et al.
methods require heating, cooling, long reaction time, tedious workup, and/or
anhydrous conditions, thus novel strategies with selectivity, efficiency, and
simple manipulation are still required in synthesis.
As a Lewis acid, SbCl3 has been used as a catalyst in organic synthesis,
including Friedel–Crafts acylation,[17] diazotization and halidization of
nucleoside derivatives,[18] conjugate reduction of 2-butene-1,4-diones with
SbCl3–LiAlH4,[19] catalytic fluorination of thiocarbonyl compounds,[20]
SbCl3–Fe–mediated allylation, reduction and acetalization of aldehydes,[21]
and conversion of nitroarenes into amines with SbCl3–NaBH4.[22]
Herein, we report a convenient and highly selective method for depro-
tection of trityl ethers with antimony trichloride. In the course of our studies
in the synthesis of nucleoside mimics, treatment of 6-O-trityl-1,2-O-isopro-
pylidene-a-D-glucofuranose 17 with a catalytic amount of SbCl3 (0.1 equiv.)
in acetonitrile and water (2 equiv.) at room temperature for 20 min afforded
the corresponding product, 1,2-O-isopropylidene-a-D-glucofuranose 18, in
91% yield. Under similar reaction conditions, detritylation of other trityl
ethers listed in Table 1 also proceeded smoothly and efficiently at room
temperature, and the relative products were also obtained in excellent
yields after simple workup and isolation through chromatography. In the
solution of dichloromethane, catalytic detritylation of compound 11 also
proceeded efficiently at rt although it took more reaction time (Table 1,
entry f). It is noteworthy that a variety of functional groups, such as
hydroxyl, benzyl (Bn) and tert-butyldiphenylsilyl (TBDPS), benzoyl (Bz),
acetyl (Ac), and p-toluenesulfonyl (Ts), are kept intact under the reaction
conditions.
Antimony trichloride dissolves in a limited amount of water to give a
clear solution; further dilution results in insoluble oxo chlorides such as
SbOCl and Sb4O5Cl2. In view of this fact, the detritylation reaction may be
catalyzed by hydrochloric acid that is generated in situ from SbCl3–H2O.
To investigate which species catalyze the hydrolysis reaction, dry acetonitrile
was used for the reaction system. Regarding both substrates 11 and 17, no
product was observed on TLC plate (Table 2) in 30 min. To our surprise, it
was observed that the amount of water affected the hydrolysis rate.
Catalytic hydrolysis of compound 11 by SbCl3 (0.1 equiv.) in acetonitrile
with water in 1.0, 5.0, and 50 molar equivalents took 20, 30, and 60 min
respectively (Table 2, compound 11). As for substrate 17, a similar phenom-
enon was observed; this substrate was not completely converted into the
corresponding alcohol in 90 min when the amount of water was more than
5 molar equivalent; the more water, the longer time it took (Table 2). Further-
more, a white precipitate was formed immediately when 50 molar equivalents
of water was added, which is probably the hydrolytic product of SbCl3,
SbOCl.[23] The characteristic yellow color of trityl cation was not observed
in the reaction solution under various conditions.[15] These results might
suggest that the catalytic effects of SbCl3 result from coordination of Sb(III)
with the oxygen atom of trityl ether rather than protic acids; thus a

Cleavage of Trityl Ethers with Antimony Trichloride
1363
Table 1. Detritylation with SbCl3 (0.1 equiv.) in acetonitrile at rt
Entry
Substratea
Producta
Time (min)
Yield(%)b
a
b
c
d
1R ¼ Bn
3R ¼ Bz
2R ¼ Bn
4R ¼ Bz
10
10
10
10
92
91
93
94
5R ¼ Ts
6R ¼ Ts
7R ¼ TBDPS
8R ¼ TBDPS
e
f
9
10
10
91
11
12
CH3CN-H2O
CH2Cl2-H2O
10
120
94
92
g
h
i
13
15
17
14
16
18
30
30
20
96
97
91
(continued)

1364
Q. Wu et al.
Table 1. Continued
Entry
j
Substratea
Producta
20
Time (min)
30
Yield(%)b
91
19
k
21
22
40
90
l
23
24
30
87
1
aAll substrates and products were identified by H NMR.
bIsolated yield after column chromatography.
proposed mechanism is described in Scheme 1. SbCl3 forms complexes with
neutral donors; in the reaction described here, complexation between SbCl3
and the ether oxygen results in polarization of the C-O bond. The cation
generated is then susceptible to nucleophilic attack by weak nucleophiles
such as water.
In conclusion, a mild and efficient method for selective cleavage of trityl
ethers with SbCl3 was demonstrated, which is compatible with a number of
functional groups under reaction conditions and provides a valuable
procedure for handling polyhydroxy compounds. It was also observed for
Table 2. Effects of water equivalents on the hydrolysis reaction catalyzed by SbCl3
(0.1 equiv.) in acetonitrile at rt
Compound 11
Compound 17
H2O
(mol equiv.)
Time (min)
Yield (%)
Time (min)
Yield (%)
0
30
20
30
40
60
0a
94
30
20
90
90
90
0a
91
1.0
5.0
30
50
93
93
91b
84
42
38b
aChecked by TLC plate.
bWhite precipitate was observed immediately after water was added.

Cleavage of Trityl Ethers with Antimony Trichloride
1365
Scheme 1. Proposed mechanism for the hydrolysis of trityl ethers catalyzed by SbCl3.
the first time that the amount of water affects the hydrolysis rate, which
presents evidence for the catalytic mechanism of detritylation reaction with
SbCl3–H2O.
General Experimental Procedure
Antimony trichloride (0.1 or 0.2 mmol) was added to a stirred solution of
substrates (1.0 mmol) in acetonitrile (10 mL) followed by the addition of
water (2.0 mmol) at room temperature. After complete conversion, a
saturated solution of sodium bicarbonate (1.0 mL) was added, and the
reaction mixture was concentrated under reduced pressure. The residue was
extracted with CH2Cl2 (3 ꢀ 10 mL). The organic layer was dried (MgSO4)
and concentrated under reduced pressure to give a crude product, which
was isolated through column chromatography on silica gel.
ACKNOWLEDGMENT
Financial support of this work from the National Natural Science Foundation
of China (30340070) is acknowledged.
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