Cesium hydroxide-catalyzed hydrothiolation of alkynyl selenides to highly stereo- and regioselectively synthesize (Z)-1-organoseleno-2-arylthio-1-alkenes

Article abstract of DOI:10.1016/j.cclet.2010.12.050

In the presence of catalytic amount of cesium hydroxide the hydrothiolation of alkynyl selenides occurred at room temperature in DMF under nitrogen atmosphere to give exclusive (Z)-1-organoseleno-2-arylthio-1-alkene in excellent yields. It could provide a

Full text of DOI:10.1016/j.cclet.2010.12.050

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 687–690
www.elsevier.com/locate/cclet
Cesium hydroxide-catalyzed hydrothiolation of alkynyl
selenides to highly stereo- and regioselectively synthesize
(Z)-1-organoseleno-2-arylthio-1-alkenes
Ai He Yu a, Ren Hua Qiu b, Nian Yuan Tan b, Li Feng Peng b, Xin Hua Xu b,
*
a Department of Biological and Chemical Engineering, Hunan Mechanical and Electrical Polytechnic, Changsha 410151, China
b College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
Received 25 October 2010
Abstract
In the presence of catalytic amount of cesium hydroxide the hydrothiolation of alkynyl selenides occurred at room temperature
in DMF under nitrogen atmosphere to give exclusive (Z)-1-organoseleno-2-arylthio-1-alkene in excellent yields. It could provide a
new and expedient way for the preparation of (Z)-1-arylseleno-2-arylthio-1-alkene.
# 2011 Xin Hua Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Hydrothiolation; Cesium hydroxide; Alkynyl selenides; (Z)-1-Organoseleno-2-arylthio-1-alkene
The synthesis and application of chalcogenide alkenes has attracted chemist attention because of their chemo-,
region-, and stereoselective reactions. The chalcogenide atom (S, Se) exercises a stabilizing effect on neighboring
positive as well as negative charges. This makes the double bond in chalcogenide alkenes responsive toward both
nucleophilic and electrophilic attack, an extremely useful feature for organic synthetic purpose [1,2]. Among the
common chalcogenide alkenes, 1,2-dichalcogenide alkenes are of much importance because of their use as bidentate
ligands in coordination chemistry, precursors of new optical materials for microelectronics, and important
intermediates for organic synthesis [1]. The unsymmetrical 1,2-dichalcogenide alkenes, which bond to two different
organochalcogen groups in the double bond, seem more significant than the corresponding symmetrical 1,2-
dichalcogenide alkenes, the reason is that the different organochalcogen groups such as organothio and organoseleno
group present different natural reactivities. Many procedures have been developed to prepare symmetrical 1,2-
dichalcogenide alkenes, for example, the transition-metal [3–12] or cesium hydroxide-catalyzed [13–15] S–S and Se–
Se bond addition to alkynes. Thiols or selenols addition to terminal alkynyls could introduce organothio or
organoseleno group in the double bond, it only suited for the preparation of mono-chalcogenide substituted alkenes,
with activated alkynes such as acetylenic esters and ketones, the addition has been performed under basic conditions,
using reagents such as KOH [16] and triethylamine [17], however, for unactivated alkynes, the use of radical initiators
[18], transition-metal catalysts [19,20], and high temperatures [21] has been required. But at high temperature or use of
* Corresponding author.
E-mail address: xhx1581@yahoo.com.cn (X.H. Xu).
1001-8417/$ – see front matter # 2011 Xin Hua Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.12.050

6[()TD$FIG] 88
A.H. Yu et al. / Chinese Chemical Letters 22 (2011) 687–690
1
H
R
CsOH (10 mol%)
DMF, R.T.
2
1
SeR
R
ArSH
+
2
SeR
ArS
2
3a~3k
1
Scheme 1. The hydrothiolation of alkynyl selenides catalyzed by cesium hydroxide.
radical initiators, the addition reactions often resulted in the formation of both Z- and E-isomers, the separation of the
Z- and E-isomers was often quite difficult. To our knowledge, there were few reports concerning the synthesis of
unsymmetrical 1,2-dichalcogenide alkenes [22]. Although the addition of unsymmetrical diorganoyl dichalcogenides
(R2S-SeR1) to terminal alkynes afforded (Z)-1-arylseleno-2-arylthio-1-alkenes with highly stereoselective [23], the
procedure needed use of water-sensitive butyl lithium, moreover it only suited for this substratum containing hydroxyl
group on the 3-position of alkynese, such as propargylic alcohols. Our group investigated the above addition catalyzed
by cesium hydroxide, and found that the R2S-SeR1 reacted with terminal alkynes in the presence of 10 mol% cesium
hydroxide at room temperature in commercial THF to give exclusive (Z)-1-arylseleno-2-arylthio-1-alkenes with
excellent yields [24]. But the reagent (R2S-SeR1) is not easily obtained. Alkynyl selenides and sulfides are important
intermediates and are readily prepared, their hydrothiolation and hydroselenation could form unsymmetrical 1,2-
dichalcogenide alkenes. In this paper, we report that cesium hydroxide catalyze addition of thiols to alkynyl selenides
to synthesize (Z)-1-organoseleno-2-arylthio-1-alkenes.
The experiments showed that the addition of thiols to alkynyl selenides could efficiently occur in the presence of
10 mol% cesium hydroxide at room temperature in commercial DMF under nitrogen atmosphere to give exclusive (Z)-
1-organoseleno-2-arylthio-1-alkenes with excellent yields (Scheme 1). The results are summarized in Table 1.
Inspection of Table 1 shows that the reaction worked well for a variety of thiols and alkynyl selenides. The results
also indicated that the reaction is not sensitive to the electronic nature of the functional groups present in the thiols and
organoselenium groups. Either electron donating or electron withdrawing groups were applied leading to
corresponding (Z)-1-organoseleno-2-arylthio-1-alkenes in high yields. The method not only suits for 3-
hydroxylpropynyl selenides but also suits for alkoxy or aryloxy propynyl selenides and phenylselenide, but it
also has some limitation, for example, almost no reaction was observed with alkynes bearing an alkyl group directed at
the triple bond, in this case we observed only traces of product.
Table 1
The synthesis of (Z)-1-arylseleno-2-arylthio-1-alkenes.
Compd.
R1
R2
ArSH
Time (h)
Yields (%)
3a
3b
3c
3d
3e
3f
CH3OCH2
CH3OCH2
CH3OCH2
CH3OCH2
CH3OCH2
CH3OCH2
CH3OCH2
HOCH2
Ph
p-CH3C6H4SH
C6H5SH
3.0
3.0
3.0
3.5
4.0
4.0
4.5
3.0
5.0
3.0
2.0
98
95
97
96
93
90
86
95
86
95
92
Ph
Ph
p-ClC6H4SH
C6H5SH
p-CH3C6H4
p-ClC6H4
CH3
C6H5SH
C6H5SH
3g
3h
3i
CH3CH2
Ph
C6H5SH
p-CH3C6H4SH
C6H5SH
HO(CH3)2C
PhOCH2
Ph
Ph
3j
3k
Ph
C6H5SH
Ph
C6H5SH
Table 2
The yields of the addition of phenyl thiol to 3-methoxy propynyl phenylselenide using various alkali metal hydroxides as catalyst.
Catalyst
Yielda (%)
LiOH
13
NaOH
45
KOH
57
RbOH
68
CsOH
98
Cs2CO3
59
a
Isolated yield.

[()TD$FIG]
A.H. Yu et al. / Chinese Chemical Letters 22 (2011) 687–690
689
1
R
H
ArSH
2
CsOH
SeR
ArS
H O
H O
2
2
1
+
R
Cs
-
+
ArS Cs
2
1
2
SeR
R
ArS
SeR
Scheme 2. The mechanism for the addition of thiol to alkynyl selenide.
We also compared the catalytic activity of other alkali metal hydroxides; the results are shown in Table 2. As is
apparent from Table 2, the cesium hydroxide showed the strongest catalytic activity for the reaction. The other alkali
metal hydroxides showed lower catalytic activity. The difference in the catalytic activity among the hydroxides is
ascribed to the differing sizes of the alkali metal ions [25]. The cesium ion, which has the largest ionic radius, is
anticipated to be only weakly paired with the counter-anion. Thus the in situ generated cesium aryl sulfide (ArSCs) is
considered to be more nucleophilic than the sulfide conjugated with other alkali metals.
A possible reaction mechanism for the addition reaction of thiols to alkynyl selenide is depicted in Scheme 2. First,
arylthiols reacted with cesium hydroxide to give cesium arylsulfides and H2O. Second, the cesium arylsulfides
underwent nucleophilic addition to the alkynyl selenides to form (Z)-1-organoseleno-2-arylthiovinylic anion, which
reacted with water to give product (Z)-1-organoseleno-2-arylthio-1-alkenes and catalyst cesium hydroxide.
The analysis of 1H NMR and 13C NMR spectra showed that all (Z)-1-organoseleno-2-arylthio-1-alkenes prepared
presented data in full agreement with their assigned structures. The stereochemistry of trisubstituted alkenes was
determined by NOESY experiments. The NOESY NMR experiment of compound 3a showed only a correlation
between the vinylic hydrogen and the methylene hydrogen bonded to the methoxy, indicating a cis relation between
them.
In conclusion, a mild, efficient and highly stereo-, and regioselective method for the synthesis of (Z)-1-
organoseleno-2-arylthio-1-alkenes was developed. The present method use air-stable cesium hydroxide as catalyst,
require neither the high temperature nor the use of expensive transition metals. It could provide a new and expedient
way for the preparation of (Z)-1-organoseleno-2-arylthio-1-alkenes. The hydroselenolation, hydrophosphination of
alkynyl sulfides and selenides as well as phosphines catalyzed by cesium hydroxide will be reported soon.
1. Experimental
Arylthiol (1.2 mmol) and cesium hydroxide (0.1 mmol) were added to a solution of alkynyl selenide (1.0 mmol) in
DMF (2.0 mL). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for a period time
listed in Table 1. Then 20 mL of water was added to the mixture and extracted with petroleum ether (3 Â 30 mL). The
combined organic phase was dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified
by flash chromatography on silica gel giving products. Compound 3a: 1H NMR (400 MHz, CDCl3): d 2.26 (s, 3H),
3.02 (s, 3H), 3.81 (s, 2H), 7.04 (d, 2H, J = 8.0 Hz), 7.08 (s, 1H), 7.23–7.25 (m, 5H), 7.50–7.52 (m, 2H). 13C NMR
(100 MHz, CDCl3): d 21.1, 57.9, 74.7, 127.7, 129.3, 129.4, 129.8, 130.5, 130.7, 131.8, 131.8, 133.0, 137.2. MS(EI), m/
z (%): 350 (M+, 100). Anal. Calcd. for C17H18OSSe: C 58.38, H 5.16, Found: C 58.45, H 5.13.
Acknowledgments
We are grateful to Natural Science Foundation of Hunan (No. 2009NK3162) and National Natural Science
Foundation of China (No. 21003040, 20372020) for financial support.

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A.H. Yu et al. / Chinese Chemical Letters 22 (2011) 687–690
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