Regioselective ring-opening reactions of 1,2-epoxides with thiols and arylselenols directly promoted by [Bmim]BF4

Article abstract of DOI:10.1016/j.tetlet.2008.08.109

Regioselective ring-opening reactions of 1,2-epoxides with ArSH and ArSeH promoted by ionic liquid [Bmim]BF₄ were investigated. A variety of β-hydroxy selenides and β-hydroxy sulfides were obtained in excellent yields (81-99%) with good regiose

Full text of DOI:10.1016/j.tetlet.2008.08.109

Tetrahedron Letters 49 (2008) 6471–6474
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Tetrahedron Letters
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Regioselective ring-opening reactions of 1,2-epoxides with
thiols and arylselenols directly promoted by [Bmim]BF4
*
Ming-Hua Yang , Guo-Bing Yan, Yun-Fa Zheng
Department of Chemistry, Lishui University, Lishui 323000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Regioselective ring-opening reactions of 1,2-epoxides with ArSH and ArSeH promoted by ionic liquid
[Bmim]BF4 were investigated. A variety of b-hydroxy selenides and b-hydroxy sulfides were obtained
in excellent yields (81–99%) with good regioselectivities using a mild, simple and environmentally benign
procedure.
Received 22 July 2007
Revised 27 August 2008
Accepted 29 August 2008
Available online 3 September 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Ring-opening reaction
Ionic liquid
b-Hydroxy selenide
b-Hydroxy sulfide
b-Hydroxy sulfides and b-hydroxy selenides are important
intermediates in medicinal chemistry and organic synthesis,1 espe-
cially for the synthesis of natural products such as leukotrienes,1c
pancratistatin,2 and schweinfurthin B.3 The effective method for
synthesis of b-hydroxy sulfides and b-hydroxy selenides is through
ring-opening reactions of epoxides with thiols and arylselenols.
While there are a few examples utilizing water or solvent-free con-
regioselective ring-opening reaction of 1,2-epoxides with thiols
and arylselenols promoted by [Bmim]BF4 in the absence of metal
salts and organic solvents.
The reaction of cyclohexene oxide with p-methylthiophenol
was initially investigated in different reaction media. The results
are shown in Table 1. It was found that trans-2-phenylthio-1-cyclo-
hexanol was obtained in only 6% yield without a catalyst in toluene
at 50 °C after 6 h (entry 1). In the presence of RTILs, such as
[Bmim]Br and [Bmim]Cl, products were obtained in 40–46% yields
(entries 2–4), indicating that these ionic liquids are moderately
effective for the ring-opening reaction. Inspired by these interest-
ing results, we utilized [Bmim]BF4 as catalyst and were pleased
to find that the yield was enhanced to 70% under the same reaction
conditions (entry 5). When the reaction was carried out at 60 °C for
6 h, the yield was further enhanced to 81% (entry 6). We then
turned our attentions to examine the substrate scope under this
optimized condition.
ditions,4 most examples involve toxic solvent and Lewis acid cata-
7
lysts, such as InCl3,5 ZnCl2,6 AlPW12O40
,
gallium complexes,8
lanthanide complexes,9 and titanium complexes.10 Compared with
the synthesis of b-hydroxy sulfides, less attention has been paid to
the synthesis of b-hydroxy selenides by the ring-opening reaction
of epoxides with ArSeH.11 Therefore, it is of significant interest to
find a mild, simple and environmentally benign method for the
synthesis of both b-hydroxy sulfides and b-hydroxy selenides.
From both environmental and economical point of view, the
concept of recyclable reaction media has gained more and more
attentions. In recent years, room temperature ionic liquids (RTILs),
which can be easily recovered and reused compared to organic
solvents, have been used in organic synthesis. Their attractive
properties, such as negligible vapor pressure, high polarity, non-
flammable, and easy handling, have made them excellent reaction
media and environmentally benign solvents.12 Moreover, some
ionic liquids even show enhancement in reaction rates and selec-
tivity.12a,13 Recently, our research was focused on the ring-opening
reaction of epoxides with nucleophiles to obtain b-hydroxy
selenides and b-hydroxyacetylene.11b,c,14 Herein, we report the
Table 1
Reaction of cyclohexene oxide with p-methylthiophenola
Entry
Ionic liquid or solvent
Temperature (°C)
Yieldb (%)
1
2
3
4
5
Toluene
50
50
50
50
60
6
43
46
70
81
[Bmim]Br
[Bmim]Cl
[Bmim]BF4
[Bmim]BF4
a
Reaction conditions: cyclohexene oxide (1.0 mmol), p-methylthiophenol
(1.1 mmol), RILTs or toluene (1.0 ml), 6 h.
* Corresponding author. Tel.: +86 578 2271 087.
E-mail address: yang1971pei@yahoo.com.cn (M.-H. Yang).
b
Isolated yields.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.109

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M.-H. Yang et al. / Tetrahedron Letters 49 (2008) 6471–6474
Table 2
a
Reaction of epoxides reacting with ArSH promoted by [Bmim]BF4
OH
+
SAr
[Bmim]BF4
60 ºC
ArSH
+
O
ArS
HO
4
1
2
3
Entry
1
Epoxide
ArSeH
Product
Time (h)
6
Yieldb (%)
81
O
H3C
H3C
H3C
SH
3aa
2a
1a
O
3ba:4ba = 4:1c
5
3
83c
85
SH
2
3
6
2a
1b
O
SH
3ca
Cl
1c
2a
O
H3C
SH
4
3da
3
93
O
O
2a
1d
O
C H
H3C
H3C
SH
5
6
n
-
3ea
5
3
83
4
9
1e
2a
O
3fa:4fa = 1:9c
91d
SH
Ph
1f
2a
O
O
O
O
O
O
SH
7
8
3db
3dc
3dd
3de
3df
3
3
5
3
3
3
96
99
87
99
91
99
O
2b
1d
1d
1d
1d
1d
1d
F
SH
O
O
O
O
O
2c
H3CO
Cl
SH
9
2d
SH
10
11
12
2e
2f
SH
SH
3dg
Br
2g
SH
O
O
13
3dh
3di
3
3
95
99
O
O
H3CO
1d
1d
2h
SH
14
2i
a
Epoxides (1.0 mmol), thiols (1.1 mmol), [Bmim]BF4 (1.0 ml).
Isolated yields.
b
c
Determined by 1H NMR and the ratio of two isomers yields.
Total yield of two isomers.
d
As listed in Table 2, all the reactions went well and gave corre-
sponding products in high yields (81–99%) when promoted by
[Bmim]BF4 at 60 °C for 3–6 h. Thiolysis of epoxides was sensitive
to the structures of both 1,2-epoxides and substituted thiophenols.
For p-methylthiophenol, the sterically hindered epoxide 1a was
found to be less reactive than other epoxides 1b, 1c, 1d, 1e, and

M.-H. Yang et al. / Tetrahedron Letters 49 (2008) 6471–6474
6473
Table 3
a
Reaction of epoxides with ArSeH promoted by [Bmim]BF4
OH
SeAr
[Bmim]BF4
+
ArSeH
O
+
ArSe
50 ºC
HO
6
5
7
1
5a: Ar = Ph-
5b: Ar = 1-naphthyl-
Entry
Epoxide
ArSeH
Product
Time (h)
Yieldb (%)
O
1
2
5a
5b
6aa
6ab
2
2
94
94
1a
O
3
4
5a
5b
6ba:7ba = 82:18c
6bb:7bb = 78:22c
2
2
93d
92d
6
1b
O
5
6
5a
5b
6ca
6cb
1
1
96
95
Cl
1c
O
O
7
8
5a
5b
6da
6db
1
1
98
98
O
O
1d
1e
C H
9
10
n
-
5a
5b
6ea
6eb
2
2
92
91
4
9
O
11
12
5a
5b
6fa:7fa = 1:4,c
6fb:7fb = 2:7c
1
1
95d
93d
Ph
1f
a
Epoxides (1.0 mmol), arylselenols (1.1 mmol), [Bmim]BF4 (1.0 ml).
Isolated yields.
b
c
Determined by 1H NMR and the ratio of two isomers yields.
Total yield of two isomers.
d
1f (entries 1–6). For the reactions of epoxide 1d, an electron-with-
drawing substituent on the thiophenol (e.g., a chloro or fluoro
group) was found to increase the reactivity, while electron-donat-
ing substituents such as methoxy and isopropyl groups were found
to lower the reactivity (entries 8–13). When the sterically hindered
naphthylthiol replaced thiophenol, the yield increased slightly (en-
try 14 vs entry 7). In term of regioselectivity, the reactions were
sensitive to the structure of epoxides. In general, for most 1,2-
epoxides except 1b and 1f, reactions were completely regioselec-
tive as typically observed with the attack of nucleophiles on the
less substituted carbon.
ArSeH was more reactive than ArSH. Except the reactions of epox-
ides 1b and 1f with ArSeH, all the reactions gave products with
exclusive regioselectivity. When the sterically hindered naphthyl-
selenol replaced thiophenol, the yields were similar. However,
the regioselectivities decreased slightly in some cases.
One of the attractive properties of ionic liquids is that they can
be recycled. Therefore, the recovery potential of [Bim]BF4 in the
reaction of 1d and 4-chlorophenylthiol was investigated. As shown
in Table 4, we are pleased to find that the reaction only showed
very slight decrease in yields in a few cycles. For example, in the
fourth run, the yield was still 96%.
Due to the importance of b-hydroxy selenides, the ring-opening
reactions of epoxides with phenylselenol and naphthylselenol di-
rectly promoted by [Bmim]BF4 were also examined. The results
are summarized in Table 3. All the reactions gave products in
excellent yields (91–98%) in 1–2 h at 50 °C, which indicated that
While the ring-opening reaction of epoxides with TMSCl and
ArHN2 directly promoted by ionic liquids have been reported,13b,13c
the catalytic mechanism is not clear yet. To study the possible
mechanism about this type of transformation, n-Bu4Cl
(100 mol %) was used as a promoter to the reaction of cyclohexene
Table 4
Reuse of [Bmim]BF4 for the reaction of epoxide 1d with p-chlorophenylthiola
SH
O
[Bmim]BF4
+
O
O
S
Cl
60 ºC, 3 h
OH
Cl
Cycle
1
99
2
99
3
97
4
96
Yieldb (%)
a
Reaction conditions: 1d (2.0 mmol), p-chlorothiophenol (2.2 mmol), [Bmim]BF4 (2.0 ml), 60 °C, 3 h. After reaction, the ionic liquid was concentrated in vacuo (5 torr for
1 h at 110 °C), and further amounts of reactants were added and next turn began.
b
Isolated yields.

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M.-H. Yang et al. / Tetrahedron Letters 49 (2008) 6471–6474
Supplementary data
Me
N
-
BF4
H
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.08.109.
-
O
ArS
N
or
R
n- But
References and notes
Figure 1. Proposed key intermediate for the ring-opening reaction promoted by
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Acknowledgments
We thank the National Natural Science Foundation of China
(No. 204720280) and the Natural Science Foundation of Zhejiang
Province (No. Y407081) for financial support.