Highly stereoselective synthesis of 1,2-diorganothio-1-alkenes via hydrothiolation of alkynyl sulfides catalyzed by cesium hydroxide

Article abstract of DOI:10.1002/cjoc.201190154

In the presence of catalytic amount of cesium hydroxide, the hydrothiolation of alkynyl sulfides occurred at room temperature in DMF under nitrogen atmosphere to afford exclusive (Z)-1,2-diorganothio-1-alkene in excellent yields. It could provide a new an

Full text of DOI:10.1002/cjoc.201190154

FULL PAPER
Highly Stereoselective Synthesis of 1,2-Diorganothio-1-alkenes
via Hydrothiolation of Alkynyl Sulfides
Catalyzed by Cesium Hydroxide
Tan, Pinga(谭平)
Yin, Xianhongb(尹显洪)
Yu, Aihea(喻爱和)
Qiu, Renhuac(邱仁华)
Peng, Lifenc(彭丽芬)
Xu, Xinhua*,c(许新华)
Zhao, Yaleic(赵亚磊)
Tang, Ruiren*,d(唐瑞仁)
a Department of Biological and Chemical Engineering, Hunan Mechanical and Electrical Polytechnic,
Changsha, Hunan 410151, China
b College of Chemistry and Ecological Engineering, Guangxi University for Nationalities,
Nanning, Guangxi 530006, China
c College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China
d College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, China
In the presence of catalytic amount of cesium hydroxide, the hydrothiolation of alkynyl sulfides occurred at
room temperature in DMF under nitrogen atmosphere to afford exclusive (Z)-1,2-diorganothio-1-alkene in excellent
yields. It could provide a new and expedient way for the preparation of symmetrical and unsymmetrical
(Z)-1,2-diorganolthio1-1-alkenes.
Keywords nucleophilic addition, regioselectivity, alkynes, hydrothiolation, cesium hydroxide, (Z)-1,2-dior-
ganolthio1-1-alkenes
Introduction
tion of mono-organothio substituted alkenes, and with
activated alkynes such as aceylenic esters and ketones,
the addition has been performed under basic conditions,
using reagents such as KOH and triethylamine,16 how-
ever, for unactivated alkynes, the use of radical initia-
tors,17 transition-metal catalysts,18-21 and high tempera-
tures22 has been required. But at high temperature or use
of radical initiators, the addition reactions often resulted
in the formation of both Z- and E-isomers, and the
separation of the Z- and E-isomers was often quite dif-
ficult. As far as we know, there are few reports con-
cerning the synthesis of unsymmetrical 1,2-diorganothio
alkenes.23
Cesium hydroxide allows the catalytic generation of
highly reactive anions which add to carbonyl groups and
carbon-carbon multiple bonds. It has received increas-
ing interest in the past few years. It has been shown re-
cently that cesium hydroxide could catalyze the reaction
of terminal alkynes with aldehydes and ketones to give
propargyl alcohols, with nitriles to give unsaturated ad-
duct,24 with phenylselenyl bromide to give alkynyl se-
lenides,25 with diarylditellides to give alkynyl tellu-
rides,23 and with diaryldiselenides and diarylsulfides to
give corresponding symmetrical (Z)-1,2-bis-(aryseleno)-
1-alkenes13,14 and (Z)-1,2-bis(arythio)-1-alkenes.15 In
this paper, we repot the cesium hydroxide-catalyzed
The synthesis and application of vinylic sulfides
have attracted chemist attention because of their chemo-,
region-, and stereoselective reactions. Moreover, the
sulfur atom exercises a stabilizing effect on neighboring
positive as well as negative charges. This makes the
double bond in vinylic sulfides responsive toward both
nucleophilic and electrophilic attack, an extremely use-
ful feature for organic synthetic purposes.1,2 Among the
common arylthio alkenes, 1,2-diorganothio alkenes are
of much importance because of their use as bidentante
ligands in coordionation chemistry, precursors of new
optical materials for microelectronics, and important
intermediates for organic synthesis.1 The unsymmetrical
1,2-diorganothio alkenes, in which the different or-
ganogroups respectively bond to two sulfur atoms, seem
more significant and interesting than the corresponding
symmetrical 1,2-diorganothio alkenes, the reason is that
the different organothio groups present different natural
and reactivity. Many procedures have been developed to
prepare symmetrical 1,2-diorganothio alkenes, for ex-
ample, the transition-metal3-12 or cesium hydroxide-
catalyzed13-15 S— S bond addition to alkynes. Thiols
addition to terminal alkynyls could introduce organothio
group in the double bond. It only suited for the prepara-
*
E-mail: xhx1581@yahoo.com.cn
Received October 27, 2010; revised December 25, 2010; accepted January 27, 2011.
Project supported by the National Natural Science Foundation of China (Nos. 21071152, 20372020).
Chin. J. Chem. 2011, 29, 765— 768
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Tan et al.
FULL PAPER
addition of thiols to alkynyl sulfides to highly regio-,
and stereoselective synthesis of (Z)-diorganothio al-
kenes.
124.6, 126.5, 130.1, 130.2, 130.8,＋132.2, 132.9, 133.4,
137.7, 137.9; MS m/z: 288 (M ). Anal. calcd for
C16H16OS2: C 66.6, H 5.59; found C 66.2, H 5.61.
(Z)-1-Ethylthio-2-phenylthio-3-hydroxypropylene
(3e) 1H NMR (CDCl3, 400 MHz) δ: 1.31 (t, J＝ 7.50
Hz, 3H), 2.30 (s, 1H), 2.85 (q, J＝ 7.50 Hz, 2H), 4.23 (s,
2H), 7.01 (s, H), 7.25— 7.30 (m, 3H), 7.52— 7.58 (m,
2H); 13C NMR (CDCl3, 100 MHz) δ: 14.6, 25.8, 65.5,
127.3, 129.1, 130.2, 132.0, 132.8, 133.7; MS m/z: 226
(M＋). Anal. calcd for C11H14OS2: C 58.4, H 6.23; found
C 58.3, H 6.25.
(Z)-1-Ethylthio-2-propylthio-3-hydroxypropylene
(3f) 1H NMR (CDCl3, 400 MHz) δ: 1.01 (t, J＝ 7.50
Hz, 3H), 1.55— 1.75 (m, 2H), 2.53 (s, 1H), 2.78 (t, J＝
7.50 Hz, 2H), 4.19 (s, 2H), 6.98 (s, H), 7.25— 7.29 (m,
3H), 7.51— 7.57 (m, 2H); 13C NMR (CDCl3, 100 MHz)
δ: 13.5, 23.5, 33.9, 65.6, 127.5, 129.1, 130.3, 132.2,
132.8, 133.9; MS m/z: 240 (M＋ ). Anal. calcd for
C12H16OS2: C 59.9, H 6.71; found C 60.0, H 6.69.
(Z)-1,2-Diphenylthio-3-methyl-3-hydroxybutylene
(3g)14 1H NMR (CDCl3, 400 MHz) δ: 1.46 (s, 6H),
2.28 (s, 1H), 7.12— 7.42 (m, 11H); 13C NMR (CDCl3,
100 MHz) δ: 29.3, 75.1, 125.4, 127.0, 127.5, 128.8,
129.0, 130.2, 134.8, 134.9, 135.1, 137.7; MS m/z: 302
(M＋). Anal. calcd for C17H18OS2: C 67.5, H 6.00; found
C 67.6, H 6.01.
Experimental
General procedure for the reaction of thiols with
alkynyl disulfide to synthesize (Z)-1,2-diorgano-
thio-1-alkene
Alkynyl sulfides (1.0 mmol) and cesium hydroxide
(0.1 mmol) were added to a solution of arylthiol (1.2
mmol) in DMF (2.0 mL). The reaction mixture was
stirred at room temperature under a nitrogen atmosphere
for a period of time listed in the Table 1. Then 20 mL of
water was added to the residue and extracted with pe-
troleum ether (10 mL× 3). The combined organic phase
was dried over anhydrous Na2SO4, and concentrated
under vacuum. The residue was purified by flash chro-
matography on silica gel giving 3a— 3k.
Characterizations of products
1H NMR and 13C NMR spectra were recorded on a
Bruker Advance 400 spectrometer in CDCl3 with TMS
as the internal standard, chemical shifts were quoted and
J value were given in Hz. Elemental analyses were per-
formed on a Yanaco MT-3CHN elemental analyser. MS
spectra were determined on an HP5989A spectrometer.
Reactions were monitored by thin layer chromatography
using silica gel F254 aluminum sheets. Alkynyl sulfides
were prepared according to the reported method.26
(Z)-1-Phenylthio-2-(m-chlorophenyl)-3-methyl-3-
hydroxybutylene (3h) 1H NMR (CDCl3, 400 MHz) δ:
1.42 (s, 6H), 2.26 (s, H), 6.98 (s, H), 7.09— 7.29 (m,
7H), 7.51— 7.57 (m, 2H); 13C NMR (CDCl3, 100 MHz)
δ: 29.1, 75.7, 124.9, 125.8, 126.5, 127.9, 129.3, 129＋.9,
133.3, 134.7, 136.8, 137.3, 138.3; MS m/z: 336 (M ).
Anal. calcd for C17H17ClOS2: C 60.6, H 5.09; found C
60.9, H 5.06.
(Z)-1,2-Diphenylthio-3-methoxpropylene
(3a)14
1H NMR (CDCl3, 400 MHz) δ: 3.30 (s, 3H), 3.94 (s,
2H), 6.99 (s, 1H), 7.21— 7.45 (m, 10H); 13C NMR
(CDCl3, 100 MHz) δ: 58.0, 74.4, 126.8, 127.1, 127.3,
129.0, 129.1, 130.0, 130.3, 133.3, 134.6, 134.9; MS m/z:
288 (M＋). Anal. calcd for C16H16OS2: C 66.6, H 5.59;
found C 66.9, H 5.52.
(Z)-1,2-Diphenylthio-3-methyl-3-phenoxypropyl-
ene (3i)14 1H NMR (CDCl3, 400 MHz) δ: 4.57 (s, 2H),
6.79 (d, J＝ 8.0 Hz, 2H), 6.93 (t, J＝ 7.2 Hz, 1H), 7.25—
7.47 (s, 9H), 7.49— 7.51 (m, 2H), 7.57— 7.60 (m, 2H);
13C NMR (CDCl3, 100 MHz) δ: 72.0, 114.8, 121.1,
127.1, 127.5, 128.5, 129.2, 129.3, 129.3, 130.4, 132.6,
132.7, 134.0, 157.9; MS m/z: 350 (M＋). Anal. calcd for
C21H18OS2: C 72.0, H 5.18; found C 71.9, H 5.19.
(Z)-1-Phenylthio-3-(p-tolyl)thio-3-phenoxypropyl-
ene (3j) 1H NMR (CDCl3, 400 MHz) δ: 2.33 (s, 3H),
4.53 (s, 2H), 6.78 (d, J＝ 8.0 Hz, 2H), 6.92 (t, J＝ 6.8 Hz,
1H), 7.09— 7.348 (m, 11H); 13C NMR (CDCl3, 100
MHz) δ: 21.4, 72.3, 115.2, 121.3, 124.9, 127.1, 127.4,
129.6, 130.4, 130.4, 133.3, 133.5, 133.8, 138.0, 138.1,
158.3; MS m/z: 364 (M＋). Anal. calcd for C22H20OS2: C
72.5, H 5.52; found C 72.8, H 5.47.
(Z)-1-Phenylthio-2-(p-tolyl)thio-3-methoxpropyl-
ene (3b) 1H NMR (CDCl3, 400 MHz) δ: 2.33 (s, 3H),
3.28 (s, 3H), 3.91 (s, 2H), 6.89 (s, 1H), 7.13 (d, J＝ 8.0
Hz, 2H), 7.26— 7.35 (m, 5H), 7.46 (d, J＝ 8.4 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ: 21.1, 57.9, 74.4, 127.2,
128.3, 129.1, 129.4, 129.8, 130.2, 130.9, 132.7, 135.2,
137.2; MS m/z: 302 (M＋). Anal. calcd for C17H18OS2: C
67.5, H 6.00; found C 67.2, H 6.05.
(Z)-1-Phenylthio-2-(p-chlorophenyl)thio-3-methox-
propylene (3c) 1H NMR (CDCl3, 400 MHz) δ: 3.32 (s,
3H), 3.96 (s, 2H), 7.03 (s, 1H), 7.07— 7.28 (m, 7H),
7.52— 7.58 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ:
58.2, 74.5, 124.3, 125.5, 126.7, 127.5, 129.7, 130＋.2,
133.3, 134.4, 136.9, 137.5, 138.4; MS m/z: 322 (M ).
Anal. calcd for C16H15ClOS2: C 59.5, H 4.68; found C
59.3, H 4.69.
(Z)-1,2-Diphenylthio-styrene (3k)14
1H NMR
(CDCl3, 400 MHz) δ: 7.07 (s, 1H), 7.21— 7.34 (m, 9H),
7.42— 7.50 (m, 6H); 13C NMR (CDCl3, 100 MHz) δ:
126.0, 126.5, 127.4, 127.6, 128.2, 128.6, 128.8, 129.2,
129.3, 130.5, 134.5, 135.2, 136.4, 138.7; MS m/z: 320
(M＋). Anal. calcd for C20H16S2: C 74.9, H 5.03; found C
75.1, H 5.27.
(Z)-1-Phenylthio-2-(p-tolyl)thio-3-hydroxypropyl-
ene (3d) 1H NMR (CDCl3, 400 MHz) δ: 2.18 (s, 1H),
2.34 (s, 3H), 4.10 (s, 2H), 6.98 (t, J＝ 1.02 Hz, 1H), 7.12
(d, J＝ 8.0 Hz, 2H), 7.25— 7.34 (m, 5H), 7.47 (d, J＝ 8.0
Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ: 21.1, 67.4,
766
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Chin. J. Chem. 2011, 29, 765— 768

Highly Stereoselective Synthesis of 1,2-Diorganothio-1-alkenes
Results and disscussion
the triple bond, in this case we observed only traces of
products.
Reactions of 3-methoxy propynyl phenyl sulfide
with phenyl thiol were tested firstly. Cesium hydroxide
(0.10 mmol) and 3-methoxy propynyl phenyl sulfide
(1.0 mmol) were added to a solution of phenyl thiol (1.2
mmol) in DMF (2.0 mL). The reaction mixture was
stirred at room temperature under nitrogen atmosphere.
After 3.0 h, the starting materials 3-methyoxy propynyl
phenyl sulfide completely disappeared by TLC analysis,
and exclusive product (Z)-1,2-diphenylthio-3-methyoxy
propylene was obtained in 98% yields.
The influence of the amount of catalyst on the reac-
tion yields was examined. When the amount of catalyst
is reduced from 10 mol% to 5.0 mol%, the yield was
decreased from 98% to 75%, while increasing catalyst
to 50 mol% did not improve the yields.
We also compared the catalytic activity of other al-
kali metal hydroxides via the addition of phenylthiol to
3-methoxy propynyl phenylsulfide; the results are
shown in Table 2. As is apparent from Table 2, the ce-
sium hydroxide showed the strongest catalytic activity
for the reaction. Hydroxides of other alkali metal such
as lithium, sodium, potassium and rubidium showed
lower or almost no activity. The difference in the cata-
lytic activity among the hydroxides is ascribed to the
differing sizes of the alkali metal ions. 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 sulfides (ArSCs) are consid-
ered to be more nucleophilic than the corresponding
sulfide conjugated with other alkali metals.
A possible reaction mechanism for the addition reac-
tion of thiols to alkynyl sulfides is depicted in Scheme 2.
First, arylthiols reacted with cesium hydroxide to give
cesium arylsulfides and H2O. Second, the cesium aryl-
sulfides underwent nucleophilic addition to the alkynyl
sulfides to form bis-arylthio vinylic anion, which re-
acted with water to give product diorganothio vinylene
and catalyst cesium hydroxide.
With the fine-tuned method in hand, we set out to
investigate the scope of the reaction. A variety of sym-
metrical and unsymmetrical (Z)-1,2-diorganothio-1-
alkenes were synthesized by reacting different alkynyl
sulfides with arylthiols (Schme 1) and the results are
summarized in Table 1.
Scheme 1 The addition of thiols to alkynyl sulfides
Schme 2 The mechanism of the hydrothiolation of alkynyl
sulfides
Inspection of Table 1 shows that the reaction worked
well for a variety of thiols and alkynyl sulfides. The
results also indicated that the reaction is not sensitive to
the electronic nature of the functional groups present in
the thiols. Either electron donating or electron with-
drawing groups were applied leading to corresponding
(Z)-1,2-diarylthio-1-alkenes in high yields. Concerning
the structure of the alkynes, we found some limitation in
this methodology. For example, no reaction was ob-
served with alkynes bearing an alkyl group directed at
Table 1 The synthesis of (Z)-1,2-diorganothio-1-alkenes
R2
ArSH
Ph C6H5SH
Entry
3a
3b
3c
R1
Time/h
3.0
Yield/%
98
CH3OCH2
CH3OCH2
CH3OCH2
HOCH2
Ph
p-CH3C6H4SH
p-ClC6H4SH
p-CH3C6H4SH
C6H5SH
3.0
95
Ph
3.0
97
3d
3e
Ph
3.0
95
HOCH2
CH3CH2
6.0
90
3f
HOCH2
CH3CH2CH2
C6H5SH
6.0
88
3g
3h
3i
HO(CH3)2C
HO(CH3)2C
PhOCH2
PhOCH2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
C6H5SH
5.0
91
m-ClC6H4SH
C6H5SH
4.0
91
3.0
94
3j
p-CH3C6H4SH
C6H5SH
3.0
95
3k
3l
3.0
93
CH3(CH2)2CH2
C6H5SH
6.0
Tracce
Chin. J. Chem. 2011, 29, 765— 768
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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767

Tan et al.
FULL PAPER
Table 2 The yields of the addition of phenyl thiol to 3-methoxy
propynyl phenylsulfide using various alkali matal hydroxides
7
8
9
Ananikov, V. P.; Kabeshov, M. A.; Beletskaya, I. P. Synlett
2005, 6, 1015.
Ananikov, V. P.; Beletskaya, I. P. Org. Biomol. Chem. 2004,
2, 284.
Entry
Base
1
2
3
4
5
6
LiOH NaOH KOH RbOH CsOH Cs2CO3
Ananikov, V. P.; Kabeshov, M. A.; Beletskaya, I. P.
Organometallics 2005, 24, 1275.
Yielda/%
a Isolated yield.
8.0
58
65
73
98
61
10 Usugi, S. I.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Org.
Lett. 2004, 6, 601.
1
The analysis of H NMR and 13C NMR spectra
showed that all vinyl sulfides prepared presented data in
full agreement with their assigned structures. The
stereochemistry of trisubstituted alkenes was deter-
mined by NOESY experiments. The NOESY NMR ex-
periment of compound 3a showed only a correlation
between the vinylic hydrogen and the methylene hy-
drogen bonded to the methoxy, indicating a cis relation
between them.
11 Dabdoub, M. J. Jr.; Guerrero, P. J. Tetrahedron Lett. 2001,
42, 7167.
12 Watanabe, S. I.; Mori, E.; Nagai, H.; Iwamura, T.; Iwama,
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13 Huang, X.; Xu, X. H.; Zheng, W. X. Synth. Commun. 1999,
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15 Zou, K. B.; Qiu, R. H.; Fang, D. W.; Liu, X. Y.; Xu, X. H.
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In summary, a mild, efficient and highly stereo-, and
regioselective method for the synthesis of (Z)-1,2-dior-
ganothio-1-akenes was developed. Compared with the
known methods, our methods use air-stable cesium hy-
droxide as catalyst, require neither the high temperature
nor the use of expensive transition metals and radical
initiators. And it could prepare not only symmetrical
(Z)-1,2-diorganolthio-1-akenes but also unsymmetrical
(Z)-1,2-diorganothio-1-akenes. It could provide a new
and expedient way for the preparation of (Z)-1,2-dior-
ganothio-1-alkenes. The hydroselenolation, hydrophos-
phination of alkynyl sulfides and selenides as well as
phosphines catalyzed by cesium hydroxide will be
reported soon.
16 Zou, K. B.; Yin, X. H.; Liu, W. Q.; Qiu, R. H.; Li, L. X.;
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Chin. J. Chem. 2011, 29, 765— 768