L-Proline promoted cross-coupling of vinyl bromide with thiols catalyzed by CuBr in ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2005.11.164

A method for the synthesis of vinyl sulfides by the coupling of vinyl bromides with thiols using the copper(I) bromide as catalyst and l-proline as ligand was reported. The best yields were obtained in the ionic liquid [Bmim]BF₄ with the retention of stereochemistry. This protocol is palladium-free, tolerates both aromatic and aliphatic thiols, possesses good selectivity between alcohol and thiol, and does not require the use of expensive or air-sensitive additives.

Full text of DOI:10.1016/j.tetlet.2005.11.164

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1217–1220
L-Proline promoted cross-coupling of vinyl bromide with
thiols catalyzed by CuBr in ionic liquid
a
a
a,b,
*
Yunfa Zheng, Xingfen Du and Weiliang Bao
a
Lishui University, Lishui, Zhejiang 323000, China
Department of Chemistry, Zhejiang University, Xi Xi Campus, Hangzhou, Zhejiang 310028, China
b
Received 6 October 2005; revised 29 November 2005; accepted 30 November 2005
Available online 27 December 2005
Abstract—A method for the synthesis of vinyl sulfides by the coupling of vinyl bromides with thiols using the copper(I) bromide as
catalyst and L-proline as ligand was reported. The best yields were obtained in the ionic liquid [Bmim]BF with the retention of
4
stereochemistry. This protocol is palladium-free, tolerates both aromatic and aliphatic thiols, possesses good selectivity between
alcohol and thiol, and does not require the use of expensive or air-sensitive additives.
ꢀ
2005 Elsevier Ltd. All rights reserved.
Alkenyl sulfides are important synthetic intermediates in
organic synthesis. They are equivalents of carbonyl
raman reported a copper-catalyzed synthesis of vinyl
sulfides via coupling reaction, but with vinyl iodides as
substrates.
1
8
compounds, and readily transformed to sulfoxides
2
and sulfones, etc. Sulfur may be also used as an auxil-
iary functional group in synthetic sequences as it can
activate the C–H bond, facilitate the loss of the a-hydro-
gen atom and stabilize the carbon anion, cation or rad-
On the other hand, ionic liquids as the novel ‘solutions’
for transition metal catalysis have been extensively stud-
9
ied in recent years. Various metal-catalyzed reactions,
3
10
icals thus formed. Also there are some other uses for
including copper-catalyzed Ullmann-type reaction,
4
11
the alkenyl sulfides. Various methods for their synthe-
and copper–proline-catalyzed formation of C–N, have
ses have been explored. Among them the addition of thi-
ols to alkynes by free radical conditions or by anionic
addition conditions is one of the most straightforward
methods to obtain vinyl sulfides, affording the anti-
Markovnikov product, usually as a stereoisomeric mix-
been demonstrated in ionic liquids(IL) and excellent
results have been obtained.
Here we wish to report a cross-coupling of vinyl
bromides with thiols catalyzed by CuBr–proline in ionic
liquid. Firstly, we explored the coupling by the reaction
of b-bromostyrene with p-methylthiophenol catalyzed
by 10 mol % CuI and 20 mol % L-proline in IL
[bmim]BF4 (bmim: 1-butyl-3-methyl imidazolium) at
110 ꢁC in the presence of K CO . The reaction pro-
5
ture. Another noteworthy methodology to add thiols to
alkynes is the addition catalyzed by transition metals
6
(
Pd, Pt, Rh, Ru, etc.) complex. The third valuable pro-
tocol to gain the vinyl sulfides is the cross-coupling of
thiols with the alkenyl halide under the catalysis of tran-
sition metal complex in a stereospecific manner. The first
example was reported by Murahashi and co-workers in
2
3
ceeded well and the vinyl sulfide was obtained in good
yield, and a little higher yield was observed when CuBr
was used as a catalyst (Table 1, entries 4 and 7). CuCl
was also tested and it was not very effective (Table 1,
entry 8). The reaction is very slow if the reaction tempera-
ture is below 90 ꢁC (Table 1, entries 5 and 6). We also
examined the effects of some common organic solvents.
Acetonitrile was ineffective for the coupling, probably
due to the low boiling point; both DMF and DMSO
were effective, but the best yield was obtained from ionic
1
979, they coupled (Z)- and (E)-b-bromostyrene with
lithium or sodium benzenethiolates using Pd(PPh ) as
3
4
7
catalyst. However, since then few reports have
appeared in the literature for the formation of vinyl
sulfur bonds by cross-coupling of vinyl halides with
thiols using transition metal catalysts. Recently, Venkata-
*
Corresponding author. Tel./fax: +86 571 88911554; e-mail: wbao@
hzcnc.com
liquid [bmim]BF . Also we screened several bases
4
including K CO , KOH, K PO and NaOH and finally
2
3
3
4
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.164

1218
Y. Zheng et al. / Tetrahedron Letters 47 (2006) 1217–1220
Table 1. Effects of CuX, temperature and solvents on the coupling of b-bromostyrene with p-methylthiophenol
H
Br
+
H
SC6H4CH3-p
SH
C
CH
CuX, Proline
C
CH
2
K CO3
CH3
1
2
3
a
Entry
Solvent
CH CN
DMF
DMSO
[Bmim]BF
[Bmim]BF
[Bmim]BF
[Bmim]BF
[Bmim]BF
CuX
React. temp (ꢁC)
React. time (h)
Yield (%)
1
2
3
4
5
6
7
8
3
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuI
Reflux
110
110
110
90
90
110
110
48
17
17
6
6
12
6
0
70
78
96
12
30
80
33
4
4
4
4
4
CuCl
15
CuX: 10 mol %; L-proline: 20 mol %; K
Isolated yield.
2
CO
3
: 4 mmol; vinyl bromide 2 mmol; thiol 2.2 mmol; ionic liq. 4 mL.
a
we found that K CO is the best base in the coupling of
bromostyrene with thiophenols.
A good stereoselectivity was also observed, for example,
when 4-methyl-b-bromostyrene is coupled with 4-isopro-
pylthiophenol, the ratio of (E)-b-(isopropylphenylthio)-
4-methylstyrene to (Z)-isomer was 94/6 (according to
2
3
The amino acids were found to be the very effective
ligands in the coupling reactions catalyzed by CuX
1
H NMR spectra); for coupling of 4-methyl-b-bromo-
1
1,12
recently.
In this reaction, we also used L-proline as
styrene with thiophenol the product ratio of (E)- to
1
an additive. Some other amino acids were also screened
and proven effective, but the best yield was obtained
with L-proline (Table 2, entry 1). If no amino acid was
added, almost no coupling product was produced.
(Z)- is 94:6 (from H NMR spectra).
Another advantage of this protocol is that the IL–pro-
line–CuBr system can be reused after a simple treatment.
Because the metal catalysts are immobilized in IL and
the separation of products from reaction mixture by
extraction will not remove the CuBr or proline or IL,
the CuBr–proline–IL mixture was vacuumed after the
product was separated, and could be re-used again
with little efficiency decline in the first several runs
(Table 4).
After the reaction condition was optimized, we started
to explore the reaction scope with various vinyl bro-
mides and thiols. The results are summarized in Table 3.
Vinyl bromide coupled to both aromatic and aliphatic
thiols in good to excellent yields, although the longer
reaction times were required for the aliphatic thiols
(
Table 3, entries 14, 15 and 16). Both electron-rich and
In summary, we have developed a mild, efficient and
comparatively cheap methodology for the synthesis of
vinyl sulfides by the coupling of vinyl bromide with thi-
ols in a highly stereoselective manner using copper(I)
bromide as catalyst and L-proline as ligand. The best
electron-poor thiols were readily reacted with the vinyl
bromide under this protocol. For 2-mercaptoethanol
where both hydroxyl and thiol groups are present, the
thiol group coupled preferentially with vinyl bromide
and no cross-coupling between the vinyl bromide and
the hydroxyl group was observed (Table 3, entries 14
and 15), therefore hydroxy-protection is not necessary.
yields were obtained in the ionic liquid [bmim]BF with
4
the retention of stereochemistry. This protocol is palla-
dium-free, tolerates both aromatic and aliphatic thiols,
Table 2. The effect of different a-amino acids in the coupling of 4-methoxy-b-bromostyrene with 4-methylthiophenol
CH CHBr
+
SH
CH CHSC H CH -p
6 4 3
CuBr, K CO , [bmim]BF
4
2
3
Amino Acids, 110˚C
OCH3
CH3
OCH3
4
2
5
a
Entry
Amino acid
Time
Yield (%)
1
2
3
4
5
6
L-Proline
Glycine
L-Analine
L-Histidine
L-Lysine
No
6
6
6
6
6
92
88
85
76
85
0
15
CuBr: 10 mol %; L-proline: 20 mol %; K
Isolated yield.
2
3
CO : 4 mmol; vinyl bromide 2 mmol; thiol 2.2 mmol; ionic liq. 4 mL.
a

Y. Zheng et al. / Tetrahedron Letters 47 (2006) 1217–1220
1219
Table 3. Copper-catalyzed cross-coupling of various aryl thiols with (E)-1-bromo-2-arylethene using the standard protocol
CuBr, Proline, K CO3
2
R1 CH CHBr + R SH
R1 CH CH SR2
2
[bmim]BF4
a
Entry
R
1
R
2
Temp (ꢁC)
110
Time (h)
Yield (%)
E:Z
7:13
8
1
2
6
6
88
96
CH3
F
110
95:5
90:10
92:8
93:7
94:6
86:14
94:6
3
4
5
6
7
8
110
110
110
120
120
120
6
6
6
8
8
8
90
95
92
88
85
96
CH3
CH3
CH3
CH3
OCH3
9
CH3
CH3
120
8
82
91:9
1
1
1
1
0
1
2
3
120
110
110
110
8
6
6
6
75
91
92
88
98:2
98:2
95:5
91:9
CH O
3
CH O
F
3
CH O
3
1
4
5
–CH
–CH
2
CH
2
2
OH
OH
110
110
10
10
83
90
94:6
95:5
1
Cl
2
CH
16
–CH
2
Ph
110
10
86
94:6
CuBr 10 mol %; L-proline 20 mol %; K
Isolated yield.
2
CO
3
4 mmol; vinyl bromide 2 mmol; thiol 2.2 mmol; ionic liq. 4 mL.
a
Table 4. Recycling of the IL–proline–CuBr system using the standard condition
H
Br
H
2
CuBr, Proline, K CO3
H
SC
H
6
H CH -p
4 3
C
C
+
p-CH C H SH
3
6
4
C
C
[
bmim]BF , 110
˚
C
Ph
4
Ph
Run
1
2
3
4
Yield (%)
96
95
90
87
possesses good selectivity between hydroxyl and thiol,
and does not require the use of expensive or air-sensitive
additives. For the typical procedures and representative
data please refer to Refs. 13 and 14.
References and notes
1. Trost, B. M.; Lavoie, A. C. J. Am. Chem. Soc. 1983, 105,
075.
. (a) Shukla, V. G.; Salgaonkar, P. D.; Akamanchi, K. G. J.
Org. Chem. 2003, 68, 5422; (b) Baciocchi, E.; Gerini, M.
F.; Lapi, A. J. Org. Chem. 2004, 69, 3586.
. (a) Thuillier, A.; Metzner, P. Sulfur Reagents in Organic
Synthesis; Academic Press: New York, 1994; (b) Gr o¨ bel,
B.-T.; Seebach, D. Synthesis 1977, 357.
5
2
Acknowledgement
3
This work was financially supported by the Natural Sci-
ence Foundation of China (No. 20225309).
4
5
. Farhat, S.; Zouev, I.; Marek, I. Tetrahedron 2004, 60,
1
329.
. (a) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnolo, P.
J. Chem. Soc., Perkin Trans. 1 1995, 1035; (b) Griesbaum,
K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273; (c) Beauche-
min, A.; Gareau, Y. Phosphorus, Sulfur, Silicon Relat.
Elem. 1998, 139, 187; (d) Benati, L.; Capella, L.; Monte-
vecchi, P. C.; Spagnolo, P. J. Org. Chem. 1994, 59, 2818; (e)
Schneider, H. J.; Bagnell, J. J. J. Org. Chem. 1961, 26, 1984.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2
005.11.164.

1220
Y. Zheng et al. / Tetrahedron Letters 47 (2006) 1217–1220
6
. (a) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, T. J. Am. [Bmim]BF (4 mL) in a 10 mL flask equipped with a
4
Chem. Soc. 1999, 121, 5108; (b) Kuniyasu, H.; Ogawa, A.;
Sato, K.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem.
Soc. 1992, 114, 5902.
. Murahashi, S.-I.; Yamamura, M.; Yanagisawa, K.-I.;
Mita, N.; Kondo, K. J. Org. Chem. 1979, 44, 2408.
. Bates, C. G.; Saejueng, P.; Doherty, M. Q.; Venkata-
raman, D. Org. Lett. 2004, 6, 5005.
magnetic stir bar, thiophenol (2.2 mmol, 0.24 g) was
added. Under N atmosphere, the mixture was stirred at
2
110 ꢁC for 6 h. The resultant product was extracted by
ethyl ether (3 · 2 mL). The product was further purified by
column chromatography (10:1 petroleum ether/ethyl
ether), yield: 0.37 g (88%).
7
8
9
8
1
14. Representative data: (E)-b-(Phenylthio)styrene: Oil;
H
. For reviews of metal-catalyzed reactions in ILs see: (a)
Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000,
NMR (300 MHz, CDCl ): d = 6.76 (d, 1H, J = 15.5 Hz),
3
1
3
6.91 (d, 1H, J = 15.5 Hz), 7.25–7.46 (m, 10H); C NMR
(75 MHz): d = 124.1, 126.7, 127.6, 128.3, 129.4, 129.8,
130.5, 132.5, 135.9, 137.2 ppm; IR (KBr): m = 3065, 3022,
39, 3772; (b) Ionic Liquids in Synthesis; Wasserscheid, P.
T., Welton, T., Eds.; Wiley-VCH Verlag GmbH & Co.:
KGaA, 2002.
ꢀ
1
1582, 1477, 1439, 1066, 943, 784, 687 cm
.
0
1
1
0. Luo, Y.; Wu, J. X.; Ren, R. X. Synlett 2003, 1734.
1. Wang, Z. M.; Bao, W. L.; Jiang, Y. Chem. Commun. 2005,
(E)-b-(4 -Fluorophenylthio)-4-methoxystyrene: mp 38–
1
3
40 ꢁC; H NMR (300 MHz, CDCl ): d = 3.77 (s, 3H),
6.64 (s, 2), 6.83 (d, 2H, J = 8.8 Hz), 7.00 (t, 2H,
J = 8.7 Hz), 7.25 (d, 2H, J = 8.8 Hz), 7.33–7.41 (m, 2H);
2849.
1
1
2. (a) Deng, W.; Zou, Y.; Wang, Y. F.; Liu, L.; Guo, Q. X.
1
3
Synlett 2004, 1254; (b) Zhu, W.; Ma, D. J. Org. Chem.
C NMR (75 MHz): d = 55.3, 114.2, 114.3, 116.3 (d,
2
005, 70, 2696; (c) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.;
J = 21.9 Hz), 120.6, 127.4, 129.3, 132.0 (d, J = 8.1 Hz),
132.3, 136.6, 159.5, 162.2 (d, J = 245.3 Hz) ppm; IR
(KBr): m = 3017, 2846, 1606, 1510, 1489, 1468, 954, 800,
Tao, F. J. Am. Chem. Soc. 1998, 120, 12459.
3. Typical procedures: To a mixture of b-bromostyrene
ꢀ
825, 630 cm . Anal. Calcd for C H FOS: C, 69.21; H,
15 13
1
(
2 mmol, 0.37 g), CuBr (0.1 mmol, 0.015 g), L-proline
(
0.2 mmol, 0.023 g), CO (4 mmol, 0.4 g) and
K
2
3
5.03. Found: C 69.50; H 4.93.