Three-component reactions of phosphorus ylides, thiophenols, and acetyl chloride for the synthesis of (β-thioacrylates)

Article abstract of DOI:10.1080/10426507.2015.1115403

The facile synthesis of 2-thioacrylates has been realized via direct three-component reactions of thiophenols, Wittig reagents, and acetyl chloride. Under transition metal-free conditions, a class of 2-thioacrylates have been synthesized with fair to exce

Full text of DOI:10.1080/10426507.2015.1115403

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Three-Component Reactions Of Phosphorus
Ylides, Thiophenols And Acetyl Chloride For The
Synthesis Of β‐Thioacrylates
Yunyun Liu & Bin Huang
To cite this article: Yunyun Liu & Bin Huang (2016): Three-Component Reactions
Of Phosphorus Ylides, Thiophenols And Acetyl Chloride For The Synthesis Of
β‐Thioacrylates, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2015.1115403
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1115403
Accepted author version posted online: 25
Jan 2016.
Submit your article to this journal
Article views: 5
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [University of California Santa Barbara]
Date: 15 March 2016, At: 04:42

ACCEPTED MANUSCRIPT
THREE-COMPONENT REACTIONS OF PHOSPHORUS YLIDES, THIOPHENOLS
AND ACETYL CHLORIDE FOR THE SYNTHESIS OF -THIOACRYLATES
*,a
a
Yunyun Liu and Bin Huang
a
Key Laboratory of Functional Small Organic Molecules, Ministry of Education, and College of
Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022 P.R. China
Email: chemliuyunyun@jxnu.edu.cn
Abstract
The facile synthesis of β-thioacrylates has been realized via direct three-component reactions of
thiophenols, Wittig reagents and acetyl chloride. Under transition metal-free conditions, a class
of β-thioacrylates have been synthesized with fair to excellent yields via cascade C = C double
2
bond and C(sp )-S bond formation.
Keywords
2
β-thioacrylate, three-component, C(sp )-S bond, transition metal-free, cascade transformation
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
Acrylates are a class of fundamental and highly useful compounds in organic chemistry. The
enriched reactivity of these compounds has enabled them with highly significant application in
organic synthesis. Typically, acrylates are frequently employed as acceptors of Michael
1
-3
4-5
additions, dienophiles and dipolarophiles in various cycloaddition reactions, reaction
6
-7
8-9
partners in cross coupling reactions, and carbon nucleophiles in Baylis-Hillman reactions, to
1
0-11
name but a few.
More notably, many acrylate-based molecules have been found as lead
1
2-14
compounds possessing invaluable biological activities.
In light of the broad utilities of acrylates in the organic, biological and material chemistry, the
synthetic research on acrylates has become an issue of extensive interest. Many distinct synthetic
1
5
16-17
approaches such as Knoevenagel condensation, propiolate hydrogenation and addition,
18-19
20
21
elimination,
Wittig olefination, and multicomponent reactions have been disclosed as
powerful tools towards acrylate synthesis. These known methods have allowed the synthesis of
acrylates of enriched structural features. However, methods allowing the practical synthesis of
β-sulfenylated acrylates are rather limited. The presently available approaches for synthesizing
β-sulfenylated acrylates mainly consist of the cross coupling reaction of thiophenols/thiols to
2
2
23-24
β-halogenated acrylates and the addition of thiol nucleophiles to propiolates or allenes.
To
the best of our knowledge, not any synthetic route employing a multicomponent reaction (MCR)
has been described in the literature. Considering the high efficiency of MCR in generating
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2
5-28
product diversity as well as its advantage of requiring simple and raw chemicals,
developing
a MCR-based methodology is of high urgency for the synthesis of β-thioacrylates. As our
continuous interest and efforts in exploring MCRs as efficient tools in the synthesis of small
2
9-31
32-34
molecules
as well as Wittig reagent based synthesis,
we report herein a three-component
protocol for the synthesis of β-thioacrylates using simple thiophenols, a Wittig reagent and acetyl
chloride as starting materials under transition metal-free conditions.
RESULTS AND DISCUSSION
In light of the known incorporation of acyl chloride and Wittig reagent to reactive allene
35
species in the presence of Et N, we tentatively performed the three-component reaction of
3
p-methylthiophenol 1a, acetyl chloride 2a and Wittig reagent 3a using potassium carbonate as
additional base and DMF as a co-solvent. This approach was found to afford β-thioacrylate 4a
with fair yield (entry 1, Table 1). A subsequent examination on the effect of the base component
suggested that cesium carbonate was the best base, and no reaction took place without using an
additional base together with Et N (entries 2-6, Table 1). Both, increasing or reducing the
3
loading of cesium carbonate gave negative result (entries 7-8, Table 1). In addition, variation of
co-solvents with different properties also failed to provide improved yields of target products
(entries 9-13, Table 1). Finally, a slightly lower yield of 4a was obtained when the temperature
was increased or lowered (entries 14-15, Table 1).
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
On the basis of the condition optimization, a variety of different thiophenols, acyl chlorides
and Wittig reagents were then employed for the reaction. As shown in Table 2, the experiments
i n t h i s s e c t i o n i m p l i e d t h a t t h e p r e s e n t t h r e e - c o m p o n e n t
protocol was generally applicable for the synthesis of β-methylthioacrylates with moderate to
excellent yield by employing different thiophenols and Wittig reagents. According to the
acquired results, the synthetic protocol exhibited satisfactory tolerance to thiophenols for the
synthesis of thioacrylates. While thiophenols containing substituents of different properties were
successfully employed in the reaction, Wittig reagents containing different electron withdrawing
groups (EWG) such as esters, cyano etc. also displayed compatibility to the synthesis. On the
other hand, the structure of the acyl chloride was found to be sensitive to the transformation.
Although acetyl chloride was able to incorporate various thiophenols and Wittig reagents, other
acyl chloride such as propionyl chloride could not take part in this three-component process,
suggesting the high impact of the hindrance of the acyl chloride component to the reaction.
CONCLUSIONS
In conclusion, the present work presents the first example on β-thioacrylate synthesis via a
one-pot, three-component approach. Under transition metal-free reaction conditions, the products
2
were formed via the tandem construction of C = C double and C(sp )-S bonds. Based on the
advantages of the present method on the atom economic and raw material-based operation, it will
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
be reasonably useful by providing a facile, practical and diversity-oriented new synthetic route to
β-thioacrylates.
EXPERIMENTAL SECTION
General information
Wittig reagents (triphenylphosphonium salts) were prepared following literature
3
8
procedures, all other chemicals were obtained from commercial sources and used directly
without further purification. Solvents used were treated following standard procedures before
1
13
use. The reaction process was monitored by TLC. The H and C NMR were recorded on a 400
1
13
MHz spectrometer in CDCl as solvent at 400 MHz ( H) and 100 MHz ( C NMR), respectively.
3
Chemical shifts were recorded in ppm by employing TMS as internal standard. HRMS data were
obtained under ESI model. Melting points were determined in a X-4A apparatus without
correcting the temperature.
General procedure for the synthesis of β-sulfenylated acrylates 4. A 25 mL
round-bottomed flask was charged with thiophenol 1 (0.5 mmol), acetyl chloride 2a (0.5 mmol),
Wittig reagent 3 (0.5 mmol), Cs CO (1.0 mmol), Et N (0.5 mmol), CH Cl (2 ml) and DMF (2
2
3
3
2
2
mL). The vessel was stirred at 100°C (reflux) in air atmosphere (1 at air balloon) for 10 h. Upon
completion (TLC), the reaction mixture was allowed to cool down to room temp. and H O (5
2
mL) was added. The resulting suspension was extracted with ethyl acetate (3 × 8 mL). The
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
organic phases were combined and dried over Na SO . After filtration and removing the solvent
2
4
at reduced pressure, the residue was subjected to silica gel column chromatography by using
1
8
00:1 (v/v) petroleum ether/ethyl acetate as the eluent to give the pure product.
1
Ethyl (E)-3-(p-tolylthio)but-2-enoate (4a). Colorless liquid. H NMR: δ = 7.37 (d, 2 H, J =
.0 Hz), 7.23 (d, 2 H, J = 8.0 Hz), 5.21 (s, 1 H), 4.07 (q, 2 H, J = 7.2 Hz), 2.42 (s, 3 H), 2.39 (s, 3
13
H), 1.21 (t, 3 H, J = 7.0 Hz); C NMR: δ = 165.5, 160.5, 140.2, 135.5, 130.6, 126.0, 110.4, 59.5,
+
2
2
1.4, 20.0, 14.3. HRMS (ESI): m/z [M+Na] calcd. for C H NaO S: 259.0769; found:
1
3
16
2
59.0758.
3
6
1
Ethyl (E)-3-(phenylthio)but-2-enoate (4b). Colorless liquid. H NMR: δ = 7.48 (d, 2 H, J
=
3
2.8 Hz), 7.42 (d, 3 H, J = 1.6 Hz), 5.28 (s, 1 H), 4.08 (q, 2 H, J = 7.2 Hz), 2.42 (s, 3 H), 1.20 (t,
1
3
H, J = 6.8 Hz); C NMR: δ = 165.2, 158.7, 135.3, 130.1, 129.5, 128.8, 111.8, 59.4, 19.8, 14.1.
1
Ethyl (E)-3-(o-tolylthio)but-2-enoate (4c). Pale yellow liquid. H NMR: δ = 7.40 (d, 1 H, J
=
7.6 Hz), 7.26 (q, 2 H, J = 5.4 Hz), 7.16 (t, 1 H, J = 7.6 Hz), 4.95 (s, 1 H), 3.98 (q, 2 H, J = 7.2
1
3
Hz), 2.36 (s, 3 H), 2.33 (s, 3 H); C NMR: δ = 165.3, 158.2, 142.8, 136.6, 130.9, 130.3, 129.1,
+
1
27.0, 110.4, 59.4, 20.2, 19.7, 14.2. HRMS (ESI): m/z [M+H] calcd. for C H O S: 237.0949;
1
3
17
2
found: 237.0944.
1
Ethyl (E)-3-(m-tolylthio)but-2-enoate (4d). Pale yellow liquid. H NMR: δ = 7.30 (d, 2 H, J
=
5.2 Hz), 7.23 (d, 2 H, J = 6.4 Hz), 5.24 (s, 1 H), 4.07 (q, 2 H, J = 7.2 Hz), 2.42 (s, 3 H), 2.36 (s,
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
13
3
H), 1.20 (t, 3 H, J = 7.0 Hz); C NMR: δ = 165.3, 159.1, 139.5, 135.8, 132.3, 130.4, 129.8,
+
1
29.4, 111.5, 59.2, 21.0, 19.8, 14.2. HRMS (ESI): m/z [M+H] calcd. for C H O S: 237.0949;
1
3
17
2
found: 237.0953.
1
Ethyl (E)-3-[(4-isopropylphenyl)thio]but-2-enoate (4e). Pale yellow liquid. H NMR: δ =
7
2
.42 (d, 2 H, J = 6.4 Hz), 7.30 (d, 2 H, J = 6.4 Hz), 5.28 (s, 1 H), 4.10 (q, 2 H, J = 6.7 Hz),
13
.99-2.93 (m, 1 H), 2.44 (s, 3 H), 1.29 (d, 6 H, J = 6.8 Hz), 1.24 (t, 3 H, J = 5.6 Hz); C NMR: δ
=
165.3, 159.8, 150.8, 135.3, 127.7, 126.8, 111.3, 59.4, 33.9, 23.6, 19.8, 14.2. HRMS (ESI): m/z
+
[
M+H] calcd. for C H O S: 265.1262; found: 265.1269.
1
5
21
2
1
Ethyl (E)-3-[(4-chlorophenyl)thio]but-2-enoate (4f). Pale yellow liquid. H NMR: δ =
7
.36-7.31 (m, 4 H), 5.18 (s, 1 H), 4.01 (q, 2 H, J = 7.0 Hz), 2.33 (s, 3 H), 1.14 (t, 3 H, J = 7.0
13
Hz); C NMR: δ = 165.0, 158.2, 136.5, 136.2, 129.9, 129.2, 112.2, 59.5, 19.7, 14.1. HRMS
+
(
ESI): m/z [M+Na] calcd. for C H ClNaO S: 279.0222; found: 279.0227.
1
2
13
2
1
Ethyl (E)-3-[(2-chlorophenyl)thio]but-2-enoate (4g). Pale yellow liquid. H NMR: δ = 7.50
(d, 1 H, J = 7.6 Hz), 7.45 (d, 1 H, J = 8.0 Hz), 7.31 (t, 1 H, J = 7.8 Hz), 7.23 (t, 1 H, J = 7.6 Hz),
1
3
5
1
.10 (s, 1H), 4.00 (q, 2 H, J = 7.2 Hz), 2.35 (s, 3 H), 1.13 (t, 3 H, J = 7.2 Hz); C NMR: δ =
65.1, 156.6, 139.5, 137.4, 131.2, 130.6, 129.1, 127.7, 112.0, 59.4, 19.6, 14.1. HRMS (ESI): m/z
+
[
M+H] calcd. for C H ClO S: 257.0403; found: 257.0398.
1
2
14
2
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
Ethyl (E)-3-[(4-bromophenyl)thio]but-2-enoate (4h). Colorless liquid. H NMR: δ = 7.49
(d, 2 H, J = 8.4 Hz), 7.28 (d, 2 H, J = 8.4 Hz), 5.15 (s, 1 H), 4.01 (q, 2 H, J = 7.0 Hz), 2.35 (s, 3
13
H), 1.15 (t, 3 H, J = 7.0 Hz); C NMR: δ = 165.0, 157.8, 136.7, 132.9, 129.2, 124.4, 112.3, 59.6,
+
1
9.8, 14.2. HRMS (ESI): m/z [M+Na] calcd. for C H BrNaO S: 322.9717; found: 322.9722.
12
13
2
1
Ethyl (E)-3-[(4-fluorophenyl)thio]but-2-enoate (4i). Colorless liquid. H NMR: δ = 7.40
(
td, 2 H, J = 6.0 Hz, J = 3.2 Hz), 7.05 (t, 2 H, J = 8.4 Hz), 5.08 (s, 1 H), 4.00 (q, 2 H, J = 7.2
1
2
1
3
Hz), 2.34 (s, 3 H), 1.13 (t, 3 H, J = 7.0 Hz); C NMR: δ = 165.1, 162.5 (d, J = 250.0 Hz), 137.5
(d, J = 23.6 Hz), 125.2 (d, J = 10.0 Hz), 111.7 (d, J = 10.4 Hz), 116.8 (d, J = 12.0 Hz), 111.3 (d,
+
J = 6.6 Hz), 59.4, 25.4, 14.2. HRMS (ESI): m/z [M+Na] calcd. for C H FNaO S: 263.0518;
1
2
13
2
found: 263.0514.
3
7
1
Methyl (E)-3-(p-tolylthio)but-2-enoate (4j). Colorless liquid. H NMR: δ = 7.38 (d, 2 H, J
1
3
=
6.4 Hz), 7.24 (d, 2 H, J = 6.8 Hz), 5.22 (s, 1 H), 3.61 (s, 3 H), 2.44 (s, 3 H), 2.40 (s, 3 H); C
NMR: δ = 165.8, 160.9, 140.3, 135.5, 130.6, 126.0, 109.9, 50.8, 21.3, 20.0.
3
6
1
Methyl (E)-3-(phenylthio)but-2-enoate (4k). Colorless liquid. H NMR: δ = 7.41-7.40 (m,
1
3
2
1
H), 7.35 (s, 3 H), 5.16 (s,1 H), 3.52 (s, 3 H), 2.36 (s, 3 H); C NMR: δ = 165.6, 159.6, 135.3,
29.6, 129.6, 129.0, 111.1, 50.5, 19.8.
1
Methyl (E)-3-(o-tolylthio)but-2-enoate (4l). Pale yellow liquid. H NMR: δ = 7.49 (d, 1 H, J
=
7.6 Hz), 7.36 (t, 1 H, J = 8.4 Hz), 7.26 (t, 1 H, J = 7.0 Hz), 5.04 (s, 1 H), 3.61 (s, 3 H), 2.47 (s,
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
3
3
5
H), 2.42 (s, 3 H); C NMR: δ = 165.8, 159.3, 142.9, 136.7, 131.1, 130.6, 128.7, 127.2, 109.2,
+
0.8, 20.4, 20.0. HRMS (ESI): m/z [M+H] calcd. for C H O S: 233.0793; found: 233.0787.
1
2
15
2
1
Methyl (E)-3-(m-tolylthio)but-2-enoate (4m). Pale yellow solid; m.p. 47-48°C. H NMR: δ
=
7.23 (d, 3 H, J = 6.4 Hz), 7.16 (d, 1 H, J = 6.0 Hz), 5.20 (s, 1 H), 3.54 (s, 3 H), 2.36 (s, 3 H),
1
3
2
2
.99 (s, 3 H); C NMR: δ = 165.6, 159.6, 139.6, 135.8, 132.3, 130.5, 129.7, 129.4, 111.0, 50.5,
+
1.0, 19.8; HRMS (ESI): m/z [M+H] calcd. for C H O S: 223.0787; found: 223.0782.
1
2
15
2
1
Methyl (E)-3-[(4-isopropylphenyl)thio]but -2-enoate (4n). Pale yellow liquid. H NMR: δ
=
7.40 (d, 2 H, J = 6.8 Hz), 7.28 (d, 2 H, J = 6.8 Hz), 5.24 (s, 1 H), 3.61 (s, 3 H), 2.97-2.90 (m, 1
1
3
H), 2.43 (s, 3 H), 1.27 (d, 6 H, J = 3.4 Hz); C NMR: δ = 165.7, 160.1, 150.9, 135.4, 131.3,
+
1
27.8, 110.5, 50.5, 33.7, 23.4, 19.8. HRMS (ESI): m/z [M+H] calcd. for C H O S: 251.1106;
1
4
19
2
found: 251.1109.
Methyl (E)-3-[(4-chlorophenyl)thio]but-2-enoate (4o). Light yellow solid. m.p. 54-57°C.
1
13
H NMR: δ = 7.34-7.29 (m, 4 H), 5.15 (s, 1 H), 3.53 (s, 3 H), 2.33 (s, 3 H); C NMR: δ = 165.4,
+
1
59.1, 136.6, 136.3, 130.0, 128.2, 111.1, 50.7, 19.8. HRMS (ESI): m/z [M+Na] calcd. for
C H ClNaO S: 265.0066; found: 265.0069.
11
11
2
Methyl (E)-3-[(2-chlorophenyl)thio]but-2-enoate (4p). Light yellow solid；m.p. 40-41°C.
H NMR: δ = 7.50 (d, 1 H, J = 7.6 Hz), 7.44 (d, 1 H, J = 8.4 Hz), 7.30 (t, 1 H, J = 7.4 Hz), 7.22
1
1
3
(
t, 1 H, J = 7.4 Hz), 5.13 (s, 1 H), 3.54 (s, 3 H), 2.35 (s, 3 H); C NMR: δ = 165.4, 157.0, 139.5,
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
+
1
37.4, 131.3, 130.6, 129.1, 127.6, 111.3, 50.5, 19.5. HRMS (ESI): m/z [M+Na] calcd. for
C H ClNaO S: 265.0066; found: 265.0067.
11
11
2
Methyl (E)-3-[(4-bromophenyl)thio]but-2-enoate (4q). Light yellow solid; m.p. 57-59°C.
H NMR: δ = 7.46 (d, 2 H, J = 8.2 Hz), 7.26 (d, 2 H, J = 7.6Hz), 5.17 (s, 1 H), 3,53 (s, 3 H), 2.33
1
1
3
(
s, 3 H); C NMR: δ = 165.4, 159.0, 136.8, 133.0, 129.0, 124.5, 111.1, 50.7, 19.8; HRMS (ESI):
+
m/z [M+Na] calcd. for C H BrNaO S: 308.9561; found: 308.9576.
11
11
2
1
Methyl (E)-3-[(4-fluorophenyl)thio]but-2-enoate (4r). Light yellow solid; m.p. 38-40°C. H
NMR: δ = 7.39 (t, 2 H, J = 6.0 Hz), 7.04 (t, 2 H, J = 8.2 Hz), 5.11 (s, 1 H), 3.53 (s, 3 H), 2.33 (s,
1
3
3
1
H); C NMR: δ = 165.4, 162.5 (d, J = 250.8), 159.8 (d, J = 34.0 Hz), 137.5 (d, J = 8.2 Hz),
25.1 (d, J = 11.9), 116.9 (d, J = 21.8), 110.9 (d, J = 4.4 Hz), 50.9, 19.6; HRMS (ESI): m/z
+
[
M+H] calcd. for C H FO S: 227.0537; found: 227.0533.
1
1
12
2
1
(
E)-3-[(4-Isopropylphenyl)thio]but-2-enenitrile (4s). Pale yellow liquid. H NMR: δ = 7.31 (d,
2
H, J = 8.0 Hz), 7.23 (d, 2 H, J = 8.2 Hz), 4.46 (s, 1 H), 2.90-2.83 (m, 1 H), 2.21 (s, 3 H), 1.18
1
3
(
d, 6 H, J = 6.4 Hz); C NMR: δ = 164.5, 151.8, 135.5, 128.3, 125.2, 117.1, 89.6, 33.9, 23.8,
+
2
1.2. HRMS (ESI): m/z [M+H] calcd. for C H ClNS: 218.1003; found: 218.0998.
1
3
16
FUNDING. This work is financially supported by the National Natural Science Foundation of
China (21202064) and Natural Science Foundation of Jiangxi Province (20142BAB213007).
1
0
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
1
2
Chen, Y.-R.; Das, U.; Liu, M.-H.; Lin, W. J. Org. Chem. 2015, 80, 1985-1992.
Kano, T.; Shirozu, F.; Akakura, M.; Maruoka, K. J. Am. Chem. Soc. 2012, 134,
1
6068-16073.
3
Gao, J.; Chen, J.-R.; Duan, S.-W.; Li, T-R.; Lu, L.-Q.; Xiao, W.-J. Asian J. Org. Chem.
014, 3, 530-535.
2
4
5
6
Hu, M.; He, X.; Niu, Z.; Yan, Z.; Zhou, F.; Shang, Y. Synthesis 2014, 46, 510-514.
Zheng, S.; Chowdhury, A.; Ojima, I.; Honda, T. Tetrahedron 2013, 69, 2052-2055.
Hu, X.-H.; Zhang, J.; Yang, X.-F.; Xu, Y.-H.; Loh, T.-P. J. Am. Chem. Soc. 2015, 137,
3
169-3172.
7
Piotrowicz, M.; Zakrzewski, J.; Métivier, R.; Brosseau, A.; Makal, A.; Woźniak, K. J. Org.
Chem. 2015, 80, 2573-2581.
8
9
Furukawa, Y.; Ogura, M. J. Am. Chem. Soc. 2014, 136, 119-121.
Tan, Y. X.; Santhanakrishnan, S.; Yang, H. Y.; Chai, C. L. L.; Tam, E. K. W. J. Org. Chem.
2
014, 79, 8059-8066.
1
0Stark, D. G.; O'Riordan, T. J. C.; Smith, A. D. Org. Lett. 2014, 16, 6496-6499.
1
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
1
1(c) Li, H.; Yang, M.; Zhang, X.; Yan, L.; Li, J.; Qi, Y. New J. Chem. 2013, 37, 1343-1349.
2Kim, J. H.; Park, E.-S.; Shim, J. H.; Kim, M.-N.; Moon, W.-S.; Chung, K.-H.; Yoon, J.-S. J.
Agric. Food Chem. 2004, 52, 7480-7483.
1
1
1
1
1
3Chan, K.; O'Brien, P. J. J. Appl. Toxicol. 2008, 28, 1004-1015.
4McCarthy, T. J.; Witz, G. Toxicology 1997, 116, 153-158.
5Wan, J.-P.; Jing, Y.; Liu, Y.; Sheng, S. RSC Adv. 2014, 4, 63997-64000.
6Schabel, T.; Belger, C.; Plietker, B. Org. Lett. 2013, 15, 2858-2861.
7Mitsudome, T.; Takahashi, Y.; Ichikawa, S.; Mizugaki, T.; Jitsukawa, K.; Kaneda, K.
Angew. Chem. Int. Ed. 2013, 52, 1481-1485.
1
1
8Kwart, H.; Gaffney, A.; Wilk, K. A. J. Org. Chem. 1983, 48, 4509-4513.
9Latorre, A.; López, I.; Ramírez, V.; Rodríguez, S.; Izquierdo, J.; González, F. V.; Vicent, C.
J. Org. Chem. 2012, 77, 5191-5197.
2
2
2
2
0Shet, J.; Desai, V.; Tilve, S. Synthesis 2004, 1859-1863.
1Zhang, Y.; Liu, Y.; Wan, J.-P. New J. Chem. 2015, 39, 1567-1569.
2Bates, C. G.; Saejueng, P.; Doherty, M. Q.; Venkataraman D. Org. Lett. 2004, 6, 5005-5008.
3Yamashita, F.; Kuniyasu, H.; Terao, J.; Kambe, N. Org. Lett. 2008, 10, 101-104.
1
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2
4Webster, S.; Young, P. C.; Barker, G.; Rosair, G. M.; Lee, A.-L. J. Org. Chem. 2015, 80,
703-1718.
1
2
2
2
2
2
3
3
5Alexander, D.; Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083-3135.
6Marson, C. M. Chem. Soc. Rev. 2012, 41, 7712-7722.
7Estévez, V.; Villacampa, M.; Menéndez, J. C. Chem. Soc. Rev. 2010, 39, 4402-4421.
8Liu, Y.; Wang, H.; Wan, J. Asian J. Org. Chem. 2013, 2, 374-386.
9Liu, Y.; Zhang, Y.; Huang, M.; Wan, J.-P. RSC Adv. 2015, 5, 46192-46196.
0Wan, J.-P.; Lin, Y.; Jiang, Y.; Xu, M.; Liu, Y. Tetrahedron 2014, 70, 7874-7880.
1Xu, Z.; Jiang, Y.; Zou, S.; Liu, Y. Phosphorus Sulfur Silicon Relat. Elem. 2014, 189,
7
91-795.
3
3
3
3
3
2Wan, J.-P.; Wang, H.; Liu, Y.; Ding, H. Org. Lett. 2014, 16, 5160-5163.
3Liu, Y.; Wang, H.; Wan, J.-P. J. Org. Chem. 2014, 79, 10599-10604.
4Huang, B.; Hu, D.; Wang, J.; Wan, J.-P.; Liu, Y. Tetrahedron Lett. 2015, 56, 2551-2554.
5Rout, L.; Harned, A. M. Chem. Eur. J. 2009, 15, 12926-12928.
6Thulasiram, V. H.; Phan, R. M.; Rivera, S.B.; Poulter, C. D. J. Org. Chem. 2006, 71,
1
739-1741.
1
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
3
3
7Walker, J. R.; Rothman, S. C.; Poulter, C. D. J. Org. Chem. 2008, 73, 726-729.
8Burling, S.; Paine, B. M.; Nama, D.; Brown, V. S.; Mahon, M. F.; Prior, T. J.; Pregosin, P.
S.; Whittlesey, M. K.; Williams, J. M. J. J. Am. Chem. Soc. 2007, 129, 1987-1995.
1
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Table 1: Experiments on optimizing of the reaction conditions
b
Entry
Base
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
dioxane
EL
Yield (%)
1
2
3
4
5
6
K CO
2
65
3
NaHCO3
NaOH
73
60
t-BuONa
Cs CO
68
82
2
3
no
trace
70
c
7
Cs CO
2
3
3
3
3
3
3
3
3
3
d
8
Cs CO
73
2
9
Cs CO
63
2
1
1
1
1
0
1
2
3
Cs CO
57
2
Cs CO
trace
trace
59
2
Cs CO
H O
2
2
Cs CO
toluene
DMF
2
e
1
4
Cs CO
70
2
f
1
5
Cs CO
DMF
80
2
a
General conditions: 1a (0.5 mmol), 2a (0.5 mmol), 3a (0.5 mmol), base (1.0 mmol) in an
additional solvent (2 mL) together with CH Cl (2 mL), Et N (0.5 mmol), stirred at 100°C for 10
2
2
3
h.
b
Yield of isolated product.
1
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
c
0
.5 mmol Cs CO was used.
2 3
d
1
.5 mmol Cs CO was used.
2 3
e
f
Reaction at 90 C.
Reaction at 110°C.
1
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 2 Scope of the three-component synthesis of sulfenylated acrylates
a
Entry
R
EWG
Product
4a
4b
4c
Yield (%)
1
2
3
4
5
6
7
8
9
4-Me
H
CO Et
82
2
CO Et
55
2
2-Me
3-Me
4-i-Pr
4-Cl
2-Cl
4-Br
4-F
CO Et
61
2
CO Et
4d
4e
58
2
CO Et
53
2
CO Et
4f
80
2
CO Et
4g
4h
4i
84
2
CO Et
70
2
CO Et
75
2
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
4-Me
H
CO Me
4j
73
2
CO Me
4k
4l
63
2
2-Me
3-Me
4-i-Pr
4-Cl
2-Cl
4-Br
4-F
CO Me
65
2
CO Me
4m
4n
4o
4p
4q
4r
56
2
CO Me
55
2
CO Me
65
2
CO Me
78
2
CO Me
69
2
CO Me
85
2
4-i-Pr
CN
4s
54
1
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Yield of isolated product.
1
8
ACCEPTED MANUSCRIPT