Decarboxylative sulfonylation of arylpropiolic acids with sulfinic acids: synthesis of (E)-vinyl sulfones

Article abstract of DOI:10.1016/j.tet.2016.01.042

Decarboxylative sulfonylation of arylpropiolic acids has been achieved by simply employing Na₂CO₃as a promoter and arenesulfinic acids as sulfonylating reagents. This simple and environmentally benign transformation offers an alternative approach and allows for easy and rapid synthesis of E-Vinyl sulfones from arylpropiolic acids and arenesufinic acids.

Full text of DOI:10.1016/j.tet.2016.01.042

Accepted Manuscript
Decarboxylative sulfonylation of arylpropiolic acids with sulfinic acids: Synthesis of
(E)-vinyl sulfones
Jatuporn Meesin, Praewpan Katrun, Vichai Reutrakul, Manat Pohmakotr, Darunee
Soorukram, Chutima Kuhakarn
PII:
S0040-4020(16)30042-4
10.1016/j.tet.2016.01.042
TET 27449
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 19 October 2015
Revised Date: 15 January 2016
Accepted Date: 25 January 2016
Please cite this article as: Meesin J, Katrun P, Reutrakul V, Pohmakotr M, Soorukram D, Kuhakarn C,
Decarboxylative sulfonylation of arylpropiolic acids with sulfinic acids: Synthesis of (E)-vinyl sulfones,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.01.042.
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Decarboxylative sulfonylation of
arylpropiolic acids with sulfinic acids:
Synthesis of (E)-vinyl sulfones
Leave this area blank for abstract info.
Jatuporn Meesin, Praewpan Katrun, Vichai Reutrakul, Manat Pohmakotr, Darunee Soorukram, Chutima
Kuhakarn*
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of
Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Decarboxylative sulfonylation of arylpropiolic acids with sulfinic acids: Synthesis of (E)-
vinyl sulfones
Jatuporn Meesin, Praewpan Katrun, Vichai Reutrakul, Manat Pohmakotr, Darunee Soorukram, Chutima
Kuhakarn*
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road, Bangkok
10400, Thailand
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Decarboxylative sulfonylation of arylpropiolic acids has been achieved by simply employing
Na2CO3 as a promoter and arenesulfinic acids as sulfonylating reagents. This simple and
environmentally benign transformation offers an alternative approach and allows for easy and
rapid synthesis of (E)-vinyl sulfones from arylpropiolic acids and arenesufinic acids.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
decarboxylative sulfonylation
arylpropiolic acids
sulfonylation
vinyl sulfones
1. Introduction
Vinyl sulfones constitute an important class of compounds
owing to their potential utility in various fields including biology,
medicines and synthetic chemistry. Vinyl sulfone scaffolds are
present in many biologically active compounds and
pharmaceuticals which display a broad range of bioactivities.1 In
view of organic synthesis, vinyl sulfones serve as versatile
synthetic synthons for various synthetic transformations.2 As a
consequence, development of new approaches for the synthesis
of vinyl sulfones is an important goal in organic chemistry. An
enormous number of synthetic routes are available toward the
synthesis of vinyl sulfones.3 Recently, decarboxylative
functionalization of carboxylic acids that involves C−heteroatom
bond forming reactions has emerged as attractive transformation
in organic synthesis.4 In particular, decarboxylative C-S bond
formation of α,β-unsaturated carboxylic acids has received a
great deal of interest.5 However, that of alkynyl carboxylic acids
has received less attention.6 Despite, being highly efficient, the
previously reported protocols toward vinyl sulfones via
decarboxylative coupling between alkynyl carboxylic acids with
either sodium sulfinates or sulfonyl hydrazides required metal
salts (Pd, Cu, Fe) (Scheme 1).
Scheme 1. Diverse approaches to access vinyl sulfones from arylpropiolic
acid derivatives.
During our study on and in the process of preparation of this
manuscript, a report on the use of the Brønsted acid-promoted
reactions of arylpropiolic acid and sodium arenesulfinates for the
synthesis of vinyl sulfones was disclosed by Mao and Zhang.7
This encouraged us to report our findings (Scheme 1). Our
research group has reported a series of efforts towards the
devlopment of efficient methods for vinyl sulfone synthesis.8 We
describe herein Na2CO3-promoted decarboxylative sulfonylation
of arylpropiolic acids with sulfinic acids in the absence of a
transition metal catalyst.
* Corresponding authors. Tel.: +66 2201 5395; fax: +66 2354 7151; e-mail
addresses: chutima.kon@mahidol.ac.th (C. Kuhakarn).
http://dx.doi.org/10.1016/j.tet.2015.xx.xxx
0040-4020/© 2015 Elsevier Ltd. All rights reserved.

2
Tetrahedron
2. Results and discussion
Table 1
ACCEPTED MANUSCRIPT
Optimization of the reaction conditionsa
Our investigation began with the search for the optimization
conditions by using the commercially available phenylpropiolic
acid (1a) and benzenesulfinic acid (2a) as benchmark substrates.
Thus, treatment of 1a (0.25 mmol) with 2a (4 equiv.) in the
presence of K2CO3 (1 equiv.) in dimethylformamide (DMF, 3
o
mL) at 100 C for 2 h resulted in the formation of (E)-vinyl
sulfone 3a in 38% isolated yield (Table 1, entry 1). Reaction
parameters were examined in order to obtain the optimized
reaction conditions. Initially, types of base were screened
including inorganic bases (Na2CO3, Cs2CO3, NaOH, and
NaHCO3) and organic bases (Et3N and pyridine) (Table 1, entries
2‒7). Vinyl sulfone 3a was obtained in higher yield (50% yield)
when Na2CO3 and NaOH were employed as the base. For the
ease of the handling, Na2CO3 was chosen as a base in the present
work. While increasing the stoichiometry of 2a from 4
equivalents to 5 equivalents did not improve the yield, lowering
the stoichiometry of 2a from 4 equivalents to 3 equivalents
significantly reduced the yield of 3a from 50% yield to 35%
yield (Table 1, entries 8–9). Reactions carried out at higher (120
Entry
Base
Solvent
Temp (oC) Time
(h)
Yieldb
(%)
38
50
39
50
29
21
22
50
35
40
27
46
Trace
8
19
46
1
2
3
4
5
6
7
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
CH3CN
Dioxane
DMA
100
100
100
100
100
100
100
100
100
120
80
100
80
100
100
100
100
2
2
2
2
2
6
3
2
2
2
2
2
5
5
5
20
2
Na2CO3
Cs2CO3
NaOH
NaHCO3
Et3N
pyridine
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
8c
9d
10
11
12
13
14
15
16
17
o
oC) or lower (80 C) temperature led to inferior results (Table 1,
entries 10‒11). Types of solvent were briefly screened (Table 1,
entries 12‒18). Among the solvents applied, DMSO gave
comparable results under similar reaction conditions. (Table 1,
entry 12 vs entry 2). The reaction also worked well in water with
comparable yield although longer reaction time (20 h) was
required (Table 1, entry 16). These promising results prompted
us to further examine the possibility of using water as a co-
solvent. Therefore, the reaction was performed in DMF-water
mixture in the ratio of 2:1 v/v (Table 1, entry 17). However,
higher content of water (DMF : H2O = 1:2 v/v) led to poorer
yield (Table 1, entry 18). On the basis of the optimization results
shown in Table 1, the standard reaction conditions were
identified as the following: arylpropiolic acid (1 equiv.), sulfinic
acid (4 equiv.), Na2CO3 (1 equiv.) in DMF-H2O (2:1 v/v; 3 mL)
at 100 oC for 2 h (Table 1, entry 17). It is noteworthy that
although we were unable to make additional improvement in the
yield of 3a, high yields were observed in some substrates studied
in this work.
H2O
DMF-H2O
(2:1 v/v)
DMF-H2O
(1:2 v/v)
53
18
Na2CO3
100
2
29
a
Reaction conditions: Phenylpropiolic acid (1a, 0.25 mmol), benzenesulfinic
acid (2a, 4 equiv.), base (1 equiv.), and solvent (3 mL).
b Isolated yields after chromatographic purification (SiO2).
c Reaction was carried out employing 2a (5 equiv.).
d Reaction was carried out employing 2a (3 equiv.).
At this stage, to gain better insight into the mechanistic
pathway, a series of control experiments were examined (Scheme
2). Initially, the reaction of phenylpropiolic acid (1a) with
benzenesulfinic acid (2a) was conducted under standard reaction
conditions in the presence of radical inhibitor, TEMPO. As can
be seen in Scheme 2, TEMPO suppressed the reaction. These
experiments implied that the reaction is probably undergoing via
a radical pathway (Scheme 2, a). The reaction carried out by
using benzenesulfinate sodium salt in place of benzenesulfinic
acid (2a) under the optimized reaction conditions did not furnish
the expected vinyl sulfone 3a (Scheme 2, b). It has been
previously reported that arylacetylenes reacted with arenesulfinic
acids to yield vinyl sulfones.9 Thus, we were aware of prior
decarboxylative-protonation to furnish phenylacetylene which
further reacts with sulfinic acid to yield the corresponding vinyl
sulfone 3a. Therefore, phenylacetylene was allowed to react with
benzenesulfinic acid (2a) under standard reaction conditions
(Scheme 2, c). This reaction did not furnish the vinyl sulfone 3a
but instead yielded the corresponding β-ketosulfone 4a in low
yield (13% yield), suggesting that the reaction does not involve
the corresponding phenylacetylene as an intermediate. Finally,
when the reaction of phenylpropiolic acid (1a) with
benzenesulfinic acid (2a) was conducted employing DMF:D2O
(2:1 v/v, 3 mL) as the solvent, a deuterated product 3a′ was
obtained almost exclusively (Scheme 2, d) (See supplementary
data for 1H and 13C data of 3a′).
With the optimized conditions in hand, we next explored the
scope of the reaction between various arylpropiolic acids 1 and
arylsulfinic acids 2, and the results are summarized in Table 2. A
collection of arylpropiolic acids and aryl sulfinic acids bearing
electronically different substituents furnished a variety of vinyl
sulfones 3a‒3y in moderate to good yields ranging from 38‒88%.
The parent phenylpropiolic acid reacted with arylsulfinic acid
bearing both electron-donating groups (R = OCH3, CH3) and
electron-withdrawing groups (R = Cl, NO2) to yield vinyl
sulfones 3a‒3e in moderate yields (48‒57% yields).
The reactions of para- and meta-halogen substituted
arylpropiolic acids also readily proceeded under standard reaction
conditions. Noteworthy, para-nitro substituted arylpropiolic acid
reacted smoothly with arylsulfinic acids 2a‒2d to yield vinyl
sulfones 3p‒3s in good to high yields (70‒88% yields). In
contrast, arylpropiolic acids bearing electron-donating groups
(CH3, OCH3) were less effective substrates, and the
corresponding vinyl sulfones 3t and 3u were obtained in
somewhat lower yields. Moderate yields (47‒63% yields) were
observed
from
the
reactions
of
3-bromo-4-
methoxylphenylpropiolic acid with arylsulfinic acids 2a‒2d.
Finally, 3-(naphthalen-2-yl)propiolic acid readily reacted with
benzenesulfinic acid (2a) to provide the corresponding vinyl
sulfone 3z in 50% yield.

3
Table 2
Substrate scopea
ACCEPTED MANUSCRIPT
O
O
S
R
F
R = H, 3f, 48%[b]
R = CH3, 3g, 44%[b]
R = OCH3, 3h, 39%
R = Cl, 3i, 50%
R = H, 3j, 70%
R’ = Br; R’’ = H, 3o, 55%
R = H, 3a, 53%
R = CH3, 3k, 49%
R = OCH3, 3l, 74%
R = Cl, 3m, 64%
R = NO2, 3n, 67%
R’ = CH3; R’’ = H, 3t, 43%[b]
R’ = H; R’’ = OCH3, 3u, 33%[b]
R = CH3, 3b, 50%
R = OCH3, 3c, 50%
R = Cl, 3d, 48%
R = NO2, 3e, 57%
O
O
S
R = H, 3p, 73%
R = CH3, 3q, 70%
R = OCH3, 3r, 82%
R = Cl, 3s, 88%
R = H, 3v, 47%
3z, 50%
R = CH3, 3w, 54%
R = OCH3, 3x, 59%
R = Cl, 3y, 63%
a Reaction conditions: 1 (0.25 mmol), 2 (4 equiv.), Na2CO3 (1 equiv.), DMF-H2O (2:1v/v; 3 mL), 100 oC, 2 h.
b Reaction time: 4 h.
O
S
O
Na2CO3 (1 equiv.)
CO2H
+
SO2H
a)
DMF-H2O (2:1 v/v)
100 oC, 2 h
3a
1a
2a (4 equiv.)
TEMPO (equiv.)
Yield (%)
1
2
3
50
19
5
O
S
O
Na2CO3 (1 equiv.)
CO2H
+
b)
c)
SO2Na
DMF-H2O (2:1 v/v)
100 oC, 2 h
3a
1a
(4 equiv.)
not observed
O
O
S
O
SO2Ph
Na2CO3 (1 equiv.)
+
SO2H
DMF-H2O (2:1 v/v)
100 oC, 2 h
1a
2a (4 equiv.)
3a
4a, 13% yield
not observed
D
O
O
S
Na2CO3 (1 equiv.)
DMF-D2O (2:1 v/v)
100 oC, 2 h
CO2H
+
d)
SO2H
D
1a
2a (4 equiv.)
3a', 47% yield
Scheme 2. Control experiments.

4
Tetrahedron
ACCEPTED MANUSCRIPT
On the basis of the control experiments described above and the
previously reported literature,7,9-10 a tentative mechanism for the
decarboxylative sulfonylation of arylpropiolic acids has been
proposed as depicted in Scheme 3. In the presence of base,
arylpropiolic acid could be deprotonated to generate carboxylate
anion A. Next, under the reaction conditions, the sulfonyl radical
B can be generated from sulfinic acid 2. Subsequently, the
sulfonyl radical B can selectively attack the alkynyl moiety of A
to produce the vinyl radical C. The high yields obtained when
para-nitrophenylpropiolic acid was employed as the starting
material imply that the step of sulfonyl radical addition to alkynyl
moiety might be the rate controlling step (Table 2). Thereafter,
the vinyl radical C can abstract a hydrogen radical from sulfinic
chromatography and visualized by UV and a solution of KMnO4.
Except for phenylpropiolic acid, all arylpropiolic acids were
prepared according to the literature procedure. Sulfinic acids
were synthesized from the acidification of sodium sulfinate salt.
Purification of the reaction products was carried out by column
chromatography on silica gel (0.063–0.200 mm). After column
chromatography, analytically pure solid was obtained by
crystallization from CH2Cl2–hexanes and acetone–hexanes.
4.2 General procedure
To a mixture of arylpropiolic acid (0.25 mmol), arenesulfinic
acid (1.0 mmol), and Na2CO3 (0.25 mmol) were added DMF (2
mL) and H2O (1 mL). The reaction mixture was stirred at 100 °C
under air atmosphere for 2 hours. After completion of the
reaction, the reaction was cooled to room temperature and was
diluted with water (10 mL). Further stirring was followed by
extraction with EtOAc (2 × 20 mL). The combined organic
extracts were washed with H2O (20 mL) and brine (20 mL), dried
(MgSO4), filtered, and concentrated (aspirator). The residue was
purified by column chromatography using EtOAc–hexanes as
eluent to afford the corresponding product.
acid to generate
D
which can subsequently undergo
decarboxylation to give vinyl anion E followed by protonation
leading to vinyl sulfone 3.
4.3 Spectroscopic data of compounds 3
4.3.1 (E)-(2-(Phenylsulfonyl)vinyl)benzene (3a).8c Colorless solid
o
(32.6 mg, 53% yield); m.p. 62–63 C. IR (neat): ν 3044, 2918,
1
1611, 1574, 1446, 1298, 1142, 1084 cm−1. H NMR (400 MHz,
CDCl3): δ = 7.95 (d, J = 7.5 Hz, 2 H), 7.69 (d, J = 15.4 Hz, 1 H),
7.61 (t, J = 7.3 Hz, 1 H), 7.56–7.52 (m, 2 H), 7.48–7.46 (m, 2 H),
7.42–7.35 (m, 3 H), 6.88 (d, J = 15.4 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 142.4 (CH), 140.6 (C), 133.3 (CH),
132.3 (C), 131.1 (CH), 129.3 (2 × CH), 129.0 (2 × CH), 128.5 (2
× CH), 127.5 (2 × CH), 127.1 (CH) ppm. HRMS (ESI) (m/z)
[C14H12O2S + Na]+: calcd. 267.0456, found 267.0455.
4.3.2 (E)-1-Methyl-4-(styrylsulfonyl)benzene (3b).8c Colorless
Scheme 3. Postulated reaction mechanism.
o
solid (31.8 mg, 50% yield); m.p. 117–118 C. IR (neat): ν 3045,
1
2920, 2851, 1650, 1613, 1595, 1449, 1302, 1140, 1084 cm−1. H
3. Conclusions
NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 8.2 Hz, 2 H), 7.66 (d, J
= 15.4 Hz, 1 H), 7.49-7.46 (m, 2 H), 7.41–7.38 (m, 3 H), 7.34 (d,
J = 8.1 Hz, 2 H), 6.85 (d, J = 15.4 HZ, 1 H), 2.43 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 144.4 (C), 141.9 (CH), 137.7
(C), 132.4 (C), 131.1 (CH), 130.0 (2 × CH), 129.0 (2 × CH),
128.5 (2 × CH), 127.7 (2 × CH), 127.6 (CH), 21.6 (CH3) ppm.
HRMS (ESI) (m/z) [C15H14O2S + Na]+: calcd. 281.0612, found
281.0618.
In summary, a facile protocol for the synthesis of vinyl
sulfones using a decarboxylation strategy via a radical pathway
has been developed. In this work, for the first time sulfinic acids
were employed to couple with a variety of arylpropiolic acids
leading to vinyl sulfones in moderate to good yields. This
reaction is selective and exclusively furnishes the corresponding
(E)-vinyl sulfones. This method provides an alternative route for
the synthesis of vinyl sulfones which are important scaffolds in
various fields.
4.3.3 (E)-1-Methoxy-4-(styrylsulfonyl)benzene (3c).8c Colorless
solid (35 mg, 50% yield); m.p. 75–76 oC. IR (neat): ν 3038, 2949,
1
2844, 1591, 1574, 1496, 1448, 1296, 1260, 1135, 1082 cm−1. H
4. Experimental
NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.9 Hz, 2 H), 7.63 (d, J
= 15.4 Hz, 1 H), 7.48–7.46 (m, 2 H), 7.39–7.37 (m, 3 H), 7.00 (d,
J = 8.9 Hz, 2 H), 6.85 (d, J = 15.4 Hz, 1 H), 3.86 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 163.5 (C), 141.3 (CH), 132.4
(C), 132.1 (C), 131.0 (CH), 129.8 (2 × CH), 129.0 (2 × CH),
128.4 (2 × CH), 127.9 (CH), 114.5 (2 × CH), 55.7 (CH3) ppm.
HRMS (ESI) (m/z) [C15H14O3S + Na]+: calcd. 297.0561, found
297.0568.
4.1 General information
1
All isolated compounds were characterized on the basis of H
NMR and 13C NMR spectroscopic data, IR spectra, and HRMS
1
data. H NMR and 13C NMR spectra were recorded on a Bruker
1
Ascend™ spectrometer. H NMR and 13C NMR chemical shifts
are reported in ppm using tetramethylsilane (TMS) or residual
nondeuterated solvent peak as an internal standard. Infrared
spectra were recorded with
a
Bruker ALPHA FT-IR
4.3.4 (E)-1-Chloro-4-(styrylsulfonyl)benzene (3d).8c White solid
spectrometer. High-resolution mass spectra (HRMS) were
recorded with a Bruker micro TOF spectrometer in the ESI
mode. Melting points were recorded with a Sanyo Gallenkamp
apparatus. Reactions were monitored by thin-layer
o
(33.7 mg, 48% yield); m.p. 78–80 C. IR (neat): ν 3087, 3053,
1
1614, 1575, 1471, 1449, 1310, 1143, 1082 cm−1. H NMR (400
MHz, CDCl3): δ = 7.88 (d, J = 8.6 Hz, 2 H), 7.69 (d, J = 15.4 Hz,

5
1 H), 7.52 (d, J = 8.6 Hz, 2 H), 7.50–7.48 (m, 2 H), 7.45–7.37
(m, 3 H), 6.84 (d, J = 15.4 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 143.0 (CH), 140.1 (C), 139.2 (C), 132.1 (C), 131.4
(CH), 129.6 (2 × CH), 129.1 (4 × CH), 128.6 (2 × CH), 126.8
(CH) ppm. HRMS (ESI) (m/z) [C14H11ClO2S + Na]+: calcd.
301.0066, found 301.0067.
CDCl ): δ = 164.4 (d, J = 252.0 Hz, C), 141.7 (CH), 140.2 (C),
3
ACCEPTED MANUSCRIPT
139.0 (C), 130.7 (d, J = 9.0 Hz, 2 × CH), 129.7 (2 × CH), 129.1
(2 × CH), 128.4 (d, J = 4.0 Hz, C), 126.6 (d, J = 2.0 Hz, CH),
116.4 (d, J = 21.0 Hz, 2 × CH) ppm. HRMS (ESI) (m/z)
[C14H10ClFO2S + Na]+: calcd. 318.9972, found 319.0052.
4.3.10 (E)-1-Chloro-3-(2-(phenylsulfonyl)vinyl)benzene (3j).8c
4.3.5 (E)-1-Nitro-4-(styrylsulfonyl)benzene (3e).7 Colorless solid
White solid (48.4 mg, 70% yield); m.p. 83–84 C. IR (neat): ν
o
o
1
(40.8 mg, 57% yield); m.p. 150–152 C. IR (neat): ν 3103, 3042,
3048, 2919, 2850, 1617, 1562, 1446, 1318, 1142, 1084 cm−1. H
2923, 1603, 1573, 1526, 1449, 1345, 1324, 1300, 1144, 1082 cm-
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.4 Hz, 2 H), 7.66–
7.55 (m, 4 H), 7.47 (s, 1 H), 7.40–7.31 (m, 3 H), 6.88 (d, J = 15.4
Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.7 (CH),
140.3 (C), 135.1 (C), 134.1 (C), 133.6 (CH), 131.0 (CH), 130.3
(CH), 129.4 (2 × CH), 128.8 (CH), 128.2 (CH), 127.7 (2 × CH),
126.8 (CH) ppm. HRMS (ESI) (m/z) [C14H11ClO2S + Na]+:
calcd. 301.0066, found 301.0069.
1
1. H NMR (400 MHz, CDCl3): δ = 8.39 (d, J = 8.9 Hz, 2 H),
8.15 (d, J = 8.9 Hz, 2 H), 7.77 (d, J = 15.4 Hz, 1 H), 7.51 (d, J =
6.5 Hz, 2 H), 7.46–7.40 (m, 3 H), 6.86 (d, J = 15.4 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 150.5 (C), 146.5 (2 × C), 145.0
(CH), 131.9 (CH), 129.2 (2 × CH), 129.0 (2 × CH), 128.8 (2 ×
CH), 125.6 (CH), 124.6 (2 × CH) ppm. HRMS (ESI) (m/z)
[C14H11NO4S + Na]+: calcd. 312.0306, found 312.0305.
4.3.11 (E)-1-Chloro-3-(2-tosylvinyl)benzene (3k).5f Colorless
4.3.6 (E)-1-Fluoro-4-(2-(phenylsulfonyl)vinyl)benzene (3f).8c
Colorless solid (32.3 mg, 48% yield); m.p. 92–93 oC. IR (neat): ν
3048, 1613, 1599, 1509, 1446, 1302, 1280, 1230, 1141, 1082
cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.8 Hz, 2 H),
7.67–7.61 (m, 2 H), 7.55 (t, J = 7.8 Hz, 2 H), 7.50–7.47 (m, 2 H),
7.08 (t, J = 8.6 Hz, 2 H), 6.80 (d, J = 15.4 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 164.3 (d, J = 251.0 Hz, C), 141.1
(CH), 140.6 (C), 133.4 (CH), 130.6 (d, J = 9.0 Hz, 2 × CH),
129.3 (2 × CH), 128.6 (d, J = 3.0 Hz, C), 127.6 (2 × CH), 127.0
(d, J = 1.9 Hz, CH), 116.3 (d, J = 22.0 Hz, 2 × CH) ppm. HRMS
(ESI) (m/z) [C14H11FO2S + Na]+: calcd. 285.0361, found
285.0360.
solid (36.2 mg, 49% yield); m.p. 92–94 C. IR (neat): ν 3061,
o
3041, 2923, 2852, 1614, 1592, 1563, 1430, 1300, 1146, 1082 cm-
1. H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8.3 Hz, 2 H),
1
7.58 (d, J = 15.4 Hz, 1 H), 7.45 (s, 1 H), 7.38–7.32 (m, 5 H), 6.86
(d, J = 15.4 Hz, 1 H), 2.43 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 144.6 (C), 140.1 (CH), 137.3 (C), 135.1 (C), 134.2
(C), 130.9 (CH), 130.3 (CH), 130.0 (2 × CH), 129.2 (CH), 128.1
(CH), 127.8 (2 × CH), 126.7 (CH), 21.6 (CH3) ppm. HRMS
(ESI) (m/z) [C15H13ClO2S + Na]+: calcd. 315.0222, found
315.0228.
4.3.12
(E)-1-Chloro-3-(2-(4-methoxyphenylsulfonyl)vinyl)-
benzene (3l).1l Colorless solid (57.3 mg, 74% yield); m.p. 71–72
oC. IR (neat): ν 3056, 2928, 2840, 1591, 1576, 1494, 1461, 1320,
4.3.7 (E)-1-Fluoro-4-(2-tosylvinyl)benzene (3g).6c White solid
o
1
(30.5 mg, 44% yield); m.p. 94–95 C. IR (neat): ν 3053, 2920,
1294, 1256, 1136, 1084 cm-1. H NMR (400 MHz, CDCl3): δ =
1
2851, 1615, 1597, 1507, 1321, 1303, 1230, 1139, 1081 cm-1. H
7.87 (d, J = 8.9 Hz, 2 H), 7.56 (d, J = 15.4 Hz, 1 H), 7.45 (s, 1
H), 7.36–7.32 (m, 3 H), 7.02 (d, J = 8.9 Hz, 2 H), 6.87 (d, J =
15.4 Hz, 1 H), 3.87 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 163.7 (C), 139.6 (CH), 135.0 (C), 134.2 (C), 131.6 (C), 130.8
(CH), 130.3 (CH), 129.9 (2 × CH), 129.5 (CH), 128.0 (CH),
126.7 (CH), 114.6 (2 × CH), 55.7 (CH3) ppm. HRMS (ESI) (m/z)
[C15H13ClO3S + Na]+: calcd. 331.0172, found 331.0170.
NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8.3 Hz, 2 H), 7.62 (d, J
= 15.4 Hz, 1 H), 7.47 (dd, J = 8.7, 5.3 Hz, 2 H), 7.35 (d, J = 8.0
Hz, 2 H), 7.08 (t, J = 8.6 Hz, 2 H), 6.78 (d, J = 15.4 Hz, 1 H),
2.43 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.3 (d, J
= 252.0 Hz, C), 144.5 (C), 140.6 (CH), 137.6 (C), 130.5 (d, J =
8.0 Hz, 2 × CH), 130.0 (2 × CH), 128.7 (d, J = 3.3 Hz, C), 127.7
(2 × CH), 127.3 (d, J = 2.4 Hz, CH), 116.3 (d, J = 22.0 Hz, 2 ×
CH), 21.6 (CH3) ppm. HRMS (ESI) (m/z) [C15H13FO2S + Na]+:
calcd. 299.0518, found 299.0519.
4.3.13 (E)-1-Chloro-3-(2-(4-chlorophenylsulfonyl)vinyl)-benzene
(3m).1l Colorless solid (50.2 mg, 64% yield); m.p. 126–129 C.
o
IR (neat): ν 3056, 2921, 2851, 1616, 1580, 1562, 1470, 1299,
1
4.3.8 (E)-1-Fluoro-4-(2-(4-methoxyphenylsulfonyl)vinyl)-benzene
1144, 1083 cm-1. H NMR (400 MHz, CDCl3): δ = 7.87 (d, J =
o
(3h).3q' White solid (23.8 mg, 39% yield); m.p. 94–95 C. IR
8.6 Hz, 2 H), 7.61 (d, J = 15.4 Hz, 1 H), 7.52 (d, J = 8.6 Hz, 2 H),
7.46 (s, 1 H), 7.40–7.31 (m, 3 H), 6.86 (d, J = 15.4 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 141.2 (CH), 140.3 (C), 138.8
(C), 135.1 (C), 133.9 (C), 131.2 (CH), 130.4 (CH), 129.7 (2 ×
CH), 129.2 (2 × CH), 128.4 (CH), 128.2 (CH), 126.8 (CH) ppm.
HRMS (ESI) (m/z) [C14H10Cl2O2S + Na]+: calcd. 334.9676, found
334.9679.
(neat): ν 3057, 2920, 2847, 1591, 1496, 1317, 1295, 1254, 1226,
1
1135, 1086 cm-1. H NMR (400 MHz, CDCl3): δ = 7.87 (d, J =
9.0 Hz, 2 H), 7.59 (d, J = 15.4 Hz, 1 H), 7.47 (dd, J = 8.7, 5.3 Hz,
2 H), 7.08 (t, J = 8.6 Hz, 2 H), 7.01 (d, J = 8.9 Hz, 2 H), 6.77 (d,
J = 15.4 Hz, 1 H), 3.87 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.2 (d, J = 252.0 Hz, C), 163.6 (C), 140.0 (CH),
132.0 (C), 130.5 (d, J = 9.0 Hz, 2 × CH), 129.9 (2× CH), 128.8
(C), 127.7 (CH), 116.3 (d, J = 22.0 Hz, 2 × CH), 114.6 (2 × CH),
55.7 (CH3) ppm. HRMS (ESI) (m/z) [C15H13FO3S + Na]+: calcd.
315.0467, found 315.0479.
4.3.14 (E)-1-Chloro-3-(2-(4-nitrophenylsulfonyl)vinyl)benzene
(3n). Pale yellow solid (54 mg, 67% yield); m.p. 130–132 oC. IR
(neat): ν 3059, 2921, 2852, 1613, 1521, 1470, 1345, 1297, 1143,
1080 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.39 (d, J = 8.9 Hz,
2 H), 8.14 (d, J = 8.9 Hz, 2 H), 7.70 (d, J = 15.4 Hz, 1 H), 7.49
4.3.9 (E)-1-Fluoro-4-(2-(4-chlorophenylsulfonyl)vinyl)benzene
o
(3i). Colorless solid (36.5 mg, 50% yield); m.p. 116–117 C. IR
(s, 1 H), 7.43–7.36 (m, 3 H), 6.88 (d, J = 15.4 Hz, 1 H) ppm. 13
C
(neat): ν 3058, 2922, 2853, 1618, 1503, 1319, 1230, 1143, 1084
cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.7 Hz, 2 H),
7.65 (d, J = 15.4 Hz, 1 H), 7.54–7.47 (m, 4 H), 7.09 (t, J = 8.6
Hz, 2 H), 6.77 (d, J = 15.4 Hz, 1 H) ppm. 13C NMR (100 MHz,
NMR (100 MHz, CDCl3): δ = 150.6 (C), 146.1 (C), 143.1 (CH),
135.3 (C), 133.5 (C), 131.7 (CH), 130.5 (CH), 129.1 (2 × CH),
128.4 (CH), 127.3 (CH), 127.1 (CH), 124.6 (2 × CH) ppm.

6
Tetrahedron
HRMS (ESI) (m/z) [C H ClNO S + Na]+: calcd. 345.9917,
(400 MHz, CDCl ): δ = 7.95 (d, J = 8.7 Hz, 2 H), 7.68–7.60 (m, 2
3
ACCEPTED MANUSCRIPT
14 10
4
found 345.9919.
H), 7.54 (t, J = 7.8 Hz, 2 H), 7.38 (d, J = 8.1 Hz, 2 H), 7.19 (d, J
= 8.0 Hz, 2 H), 6.81 (d, J = 15.4 Hz, 1 H), 2.37 (s, 3 H) ppm. 13
C
4.3.15 (E)-1-Bromo-4-(2-(phenylsulfonyl)vinyl)benzene (3o).8c
Colorless solid (44.3 mg, 55% yield); m.p. 138–139 oC. IR
(neat): ν 3054, 1610, 1582, 1481, 1446, 1397, 1305, 1141, 1067
cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.9 Hz, 2 H),
7.65–7.51 (m, 6 H), 7.34 (d, J = 8.5 Hz, 2 H), 6.86 (d, J = 15.4
Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.0 (CH),
140.4 (C), 133.5 (CH), 132.4 (2 × CH), 131.2 (C), 129.9 (2 ×
CH), 129.4 (2 × CH), 128.0 (CH), 127.7 (2 × CH), 125.6 (C)
ppm. HRMS (ESI) (m/z) [C14H11BrO2S + Na]+: calcd. 346.9540,
found 346.9543.
NMR (100 MHz, CDCl3): δ = 142.5 (CH), 141.9 (C), 140.9 (C),
133.3 (CH), 129.8 (2 × CH), 129.6 (C), 129.3 (2 × CH), 128.6 (2
× CH), 127.6 (2 × CH), 126.0 (CH), 21.5 (CH3) ppm. HRMS
(ESI) (m/z) [C15H14O2S + Na]+: calcd. 281.0612, found 281.0615.
4.3.21 (E)-1-Methoxy-3-(2-(phenylsulfonyl)vinyl)benzene (3u).8c
Colorless solid (22.4 mg, 33% yield); m.p. 101–102 oC. IR
(neat): ν 3075, 3046, 3005, 2838, 1598, 1584, 1446, 1300, 1270,
1
1144, 1083 cm−1. H NMR (400 MHz, CDCl3): δ = 7.95 (d, J =
8.9 Hz, 2 H), 7.68–7.61 (m, 2 H), 7.55 (t, J = 7.8 Hz, 2 H), 7.30
(t, J = 7.9 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 6.99–6.95 (m, 2 H),
6.86 (d, J = 15.4 Hz, 1 H), 3.81 (s, 3 H) ppm. 13C NMR (100
MHz, CDCl3): δ = 159.9 (C), 142.4 (CH), 140.6 (C), 133.6 (C),
133.4 (CH), 130.1 (CH), 129.3 (2 × CH), 127.6 (2 × CH), 127.5
(CH), 121.2 (CH), 117.1 (CH), 113.3 (CH), 55.3 (CH3) ppm.
HRMS (ESI) (m/z) [C15H14O3S + Na]+: calcd. 297.0561, found
297.0567.
4.3.16 (E)-1-Nitro-4-(2-(phenylsulfonyl)vinyl)benzene (3p).8c
Yellow solid (53.1 mg, 73% yield); m.p. 152–153 oC. IR (neat): ν
1
3055, 1592, 1509, 1446, 1337, 1307, 1148, 1085 cm−1. H NMR
(400 MHz, acetone-d6): δ = 8.29 (d, J = 8.8 Hz, 2 H), 8.05–7.98
(m, 4 H), 7.81 (d, J = 15.5 Hz, 1 H), 7.77–7.73 (m, 1 H), 7.70–
7.66 (m, 2 H), 7.61 (d, J = 15.5 Hz, 1 H) ppm. 13C NMR (100
MHz, acetone-d6): δ 150.0 (C), 141.8 (C), 140.4 (CH), 140.1 (C),
134.8 (CH), 133.5 (CH), 130.9 (2 × CH), 130.6 (2 × CH), 128.8
(2 × CH), 125.0 (2 × CH) ppm. HRMS (ESI) (m/z) [C14H11NO4S
+ Na]+: calcd. 312.0306, found 312.0309.
4.3.22
(E)-1-Bromo-3-methoxy-4-(2-(phenylsulfonyl)vinyl)-
benzene (3v). Colorless solid (41.1 mg, 47% yield); m.p. 158–
o
161 C. IR (neat): ν 3048, 2940, 2843, 1607, 1495, 1301, 1283,
1
1138, 1081 cm-1. H NMR (400 MHz, CDCl3): δ = 7.93 (d, J =
4.3.17 (E)-1-Nitro-4-(2-tosylvinyl)benzene (3q).5f Pale yellow
7.3 Hz, 2 H), 7.69 (d, J = 2.1 Hz, 1 H), 7.63–7.53 (m, 4 H), 7.40
(dd, J = 8.5, 2.1 Hz, 1 H), 6.89 (d, J = 8.6 Hz, 1 H), 6.73 (d, J =
15.4 Hz, 1 H), 3.92 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 158.1 (C), 140.7 (C), 140.6 (CH), 133.3 (CH), 133.0 (CH),
129.7 (CH), 129.3 (2 × CH), 127.6 (2 × CH), 126.2 (C), 126.0
(CH), 112.4 (C), 111.8 (CH), 56.4 (CH3) ppm. HRMS (ESI)
(m/z) [C15H13BrO3S + Na]+: calcd. 376.9646, found 376.9649.
o
solid (52.7 mg, 70% yield); m.p. 166–168 C. IR (neat): ν 3052,
1
2921, 2851, 1595, 1514, 1341, 1301, 1287, 1144, 1082 cm-1. H
NMR (400 MHz, acetone-d6): δ = 8.29 (d, J = 8.8 Hz, 2 H), 8.02
(d, J = 8.8 Hz, 2 H), 7.85 (d, J = 8.3 Hz, 2 H), 7.77 (d, J = 15.5
Hz, 1 H), 7.58 (d, J = 15.5 Hz, 1 H), 7.48 (d, J = 8.2 Hz, 2 H),
2.44 (s, 3 H) ppm. 13C NMR (100 MHz, acetone-d6): δ = 150.0
(C), 145.8 (C), 140.2 (C), 139.8 (CH), 138.8 (C), 133.8 (CH),
131.1 (2 × CH), 130.8 (2 × CH), 128.8 (2 × CH), 125.0 (2 × CH),
21.6 (CH3) ppm. HRMS (ESI) (m/z) [C15H13NO4S + Na]+: calcd.
326.0463, found 326.0466.
4.3.23 (E)-1-Bromo-3-methoxy-4-(2-tosylvinyl)benzene (3w).
o
Pale yellow solid (49.3 mg, 54% yield); m.p. 166–168 C. IR
(neat): ν 3066, 2920, 2851, 1607, 1594, 1493, 1462, 1287, 1261,
1
1135, 1080 cm-1. H NMR (400 MHz, CDCl3): δ = 7.81 (d, J =
4.3.18 (E)-1-Nitro-4-(2-(4-methoxyphenylsulfonyl)vinyl)-benzene
8.3 Hz, 2 H), 7.67 (d, J = 2.0 Hz, 1 H), 7.52 (d, J = 15.4 Hz, 1 H),
7.39 (dd, J = 8.6, 2.0 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 2 H), 6.88 (d,
J = 8.6 Hz, 1 H), 6.71 (d, J = 15.3 Hz, 1 H), 3.91 (s, 3 H), 2.43 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.9 (C), 144.3 (2
× C), 140.1 (CH), 137.7 (C), 132.9 (CH), 129.9 (2 × CH), 129.6
(CH), 127.6 (2 × CH), 126.3 (CH), 112.4 (C), 111.8 (CH), 56.4
(CH3), 21.6 (CH3) ppm. HRMS (ESI) (m/z) [C16H15BrO3S + Na]+:
calcd. 390.9803, found 390.9807.
o
(3r).5f White solid (64.3 mg, 82% yield); m.p. 186–188 C. IR
(neat): ν 3111, 3083, 3056, 2921, 2845, 1590, 1521, 1493, 1341,
1295, 1253, 1136, 1088 cm-1. 1H NMR (400 MHz, acetone-d6): δ
= 8.29 (d, J = 8.9 Hz, 2 H), 8.01 (d, J = 8.8 Hz, 2 H), 7.90 (d, J =
9.0 Hz, 2 H), 7.73 (d, J = 15.5 Hz, 1 H), 7.56 (d, J = 15.5 Hz, 1
H), 7.17 (d, J = 9.0 Hz, 2 H), 3.91 (s, 3 H) ppm. 13C NMR (100
MHz, acetone-d6): δ = 165.0 (C), 149.9 (C), 140.3 (C), 139.1
(CH), 134.2 (CH), 133.1 (CH), 131.1 (2 × CH), 130.8 (2 × CH),
125.0 (2 × CH), 115.8 (2 × CH), 56.4 (CH3) ppm. HRMS (ESI)
(m/z) [C15H13NO5S + Na]+: calcd. 342.0412, found 342.0425.
4.3.24
(E)-1-Bromo-3-methoxy-4-(2-(4-
methoxyphenylsulfonyl)vinyl)benzene (3x). White solid (57 mg,
o
59% yield); m.p. 155–158 C. IR (neat): ν 3054, 2918, 2846,
1
4.3.19
(E)-1-Nitro-4-(2-(4-chlorophenylsulfonyl)vinyl)benzene
1591, 1492, 1291, 1254, 1133, 1085 cm-1. H NMR (400 MHz,
o
(3s). Pale yellow solid (70.5 mg, 88% yield); m.p. 176–178 C.
IR (neat): ν 3112, 3085, 3057, 2922, 2850, 1593, 1520, 1473,
1341, 1307, 1143, 1085 cm-1. 1H NMR (400 MHz, acetone-d6): δ
= 8.30 (d, J = 8.8 Hz, 2 H), 8.04–7.98 (m, 4 H), 7.83 (d, J = 15.5
Hz, 1 H), 7.72 (d, J = 8.7 Hz, 2 H), 7.63 (d, J = 15.5 Hz, 1 H)
ppm. 13C NMR (100 MHz, acetone-d6): δ = 150.1 (C), 140.9 (CH),
140.6 (C), 140.5 (C), 140.0 (C), 133.0 (CH), 131.0 (2 × CH), 130.8
(2 × CH), 130.7 (2 × CH), 125.0 (2 × CH) ppm. HRMS (ESI) (m/z)
[C14H10ClNO4S + Na]+: calcd. 345.9917, found 345.9929.
CDCl3): δ = 7.85 (d, J = 9.0 Hz, 2 H), 7.67 (d, J = 2.1 Hz, 1 H),
7.50 (d, J = 15.4 Hz, 1 H), 7.39 (dd, J = 8.6, 2.2 Hz, 1 H), 7.00
(d, J = 9.0 Hz, 2 H), 6.89 (d, J = 8.6 Hz, 1 H), 6.71 (d, J = 15.3
Hz, 1 H), 3.92 (s, 3 H), 3.87 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 163.5 (C), 157.9 (C), 139.5 (CH), 132.9 (CH), 132.2
(C), 129.8 (2 × CH), 129.6 (CH), 126.7 (CH), 126.4 (C), 114.5 (2
× CH), 112.4 (C), 111.8 (CH), 56.4 (CH3), 55.7 (CH3) ppm.
HRMS (ESI) (m/z) [C16H15BrO4S + Na]+: calcd. 406.9752, found
406.9748.
4.3.20 (E)-1-Methyl-4-(2-(phenylsulfonyl)vinyl)benzene (3t).8c
4.3.25
(E)-1-Bromo-3-methoxy-4-(2-(4-chlorophenylsulfonyl)-
o
White solid (27.7 mg, 43% yield); m.p. 118–120 C. IR (neat): ν
vinyl)benzene (3y). White solid (61 mg, 63% yield); m.p. 132–
1
o
3053, 2918, 1604, 1510, 1446, 1306, 1143, 1082 cm−1. H NMR
135 C. IR (neat): ν 3068, 2949, 2850, 1612, 1591, 1495, 1439,

7
1
1399, 1299, 1284, 1269, 1136, 1083 cm-1. H NMR (400 MHz,
References and notes
ACCEPTED MANUSCRIPT
CDCl3): δ = 7.86 (d, J = 8.6 Hz, 2 H), 7.69 (d, J = 2.1 Hz, 1 H),
7.56 (d, J = 15.4 Hz, 1 H), 7.51 (d, J = 8.6 Hz, 2 H), 7.41 (dd, J =
8.5, 2.1 Hz, 1 H), 6.90 (d, J = 8.6 Hz, 1 H), 6.70 (d, J = 15.3 Hz,
1 H), 3.93 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.2
(C), 141.2 (CH), 140.0 (C), 139.3 (C), 133.0 (CH), 129.8 (CH),
129.6 (2 × CH), 129.1 (2 × CH), 126.0 (C), 125.5 (CH), 112.5
(C), 111.9 (CH), 56.4 (CH3) ppm. HRMS (ESI) (m/z)
[C15H12BrClO3S + Na]+: calcd. 410.9256, found 410.9252.
1. (a) Liu, S.; Hanzlik, R. P. J. Med. Chem. 1992, 35, 1067–1075; (b)
Palmer, J. T.; Rasnick, D.; Klaus, J. L.; Brömme, D. J. Med. Chem. 1995,
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K. A.; McKerrow, J. H.; Hansell, E. J. Am. Chem. Soc. 1998, 120,
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Frankel, B. A.; Bentley, M.; Kruger, R. G.; McCafferty, D. G. J. Am.
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der Veken, P.; Krishtal, A.; Van Alsenoy, C.; Westrop, G. D.; Mottram,
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4.3.26 (E)-2-(2-(Phenylsulfonyl)vinyl)naphthalene (3z).8c White
o
solid (36.7 mg, 50% yield); m.p. 89–90 C. IR (neat): ν 3046,
1
2919, 1611, 1445, 1304, 1286, 1139, 1083 cm−1. H NMR (400
MHz, CDCl3): δ = 8.00 (d, J = 7.3 Hz, 2 H), 7.94 (s, 1 H), 7.87–
7.81 (m, 4 H), 7.63 (t, J = 7.4 Hz, 1 H), 7.58–7.51 (m, 5 H), 6.98
(d, J = 15.3 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
142.5 (CH), 140.8 (C), 134.5 (C), 133.4 (CH), 133.1 (C), 130.9
(CH), 129.8 (C), 129.3 (2 × CH), 128.9 (CH), 128.7 (CH), 127.8
(2 × CH), 127.6 (2 × CH), 127.2 (CH), 127.0 (CH), 123.4 (CH)
ppm. HRMS (ESI) (m/z) [C18H14O2S + Na]+: calcd. 317.0612,
found 317.0610.
Park, K. D. J. Med. Chem. 2014, 57, 1473–1487
.
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Tetrahedron 2001, 57, 201–209; (d) Arjona, O.; Menchaca, R.; Plumet, J.
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Murphree, S. S. J. Org. Chem. 2003, 68, 6238–6250; (f) Llamas, T.;
Arrayás, R. G.; Carretero, J. C. Org. Lett. 2006, 8, 1795–1798; (g)
Wardrop, D. J.; Fritz, J. Org. Lett. 2006, 8, 3659–3662; (h) Noshi, M. N.;
Elawa, A.; Torres, E.; Fuchs, P. L. J. Am. Chem. Soc. 2007, 129, 11242–
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Angew. Chem., Int. Ed. 2007, 46, 9261–9264; (j) Esteves, A. P.; Silva,
M. E.; Rodrigues, L. M.; Oliveira-Campos, A. M. F.; Hrdina, R.
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Chem. 2008, 10, 327–332; (l) Kumamoto, H.; Deguchi, K.; Wagata, T.;
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4.4 Preparation of compound 3a'
To a mixture of 3-phenylpropiolic acid (36.5 mg, 0.25 mmol),
benzenesulfinic acid (142.2 mg, 1.0 mmol), and Na2CO3 (26.9
mg, 0.25 mmol) were added DMF (2 mL) and D2O (1 mL). The
reaction mixture was stirred at 100 °C under air atmosphere for 2
hours. After completion of the reaction, the reaction was cooled
to room temperature and was diluted with water (10 mL). Further
stirring was followed by extraction with EtOAc (2 × 20 mL). The
combined organic extracts were washed with H2O (20 mL) and
brine (20 mL), dried (MgSO4), filtered, and concentrated
(aspirator). The residue was purified by column chromatography
using EtOAc–hexanes as eluent to afford 3a'.
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(E)-(1,2-deutero-2-(phenylsulfonyl)vinyl)benzene (3a′).7 White
solid (29 mg, 47% yield); m.p. 74–76 oC. IR (neat): ν 3057, 1568,
1
1446, 1295, 1144, 1086 cm−1. H NMR (400 MHz, CDCl3): δ =
7.96 (d, J = 7.4 Hz, 2 H), 7.64–7.60 (m, 1 H), 7.57–7.53 (m, 2
H), 7.50–7.48 (m, 2 H), 7.44–7.37 (m, 3 H) ppm. 13C NMR (100
MHz, CDCl3): δ = 142.4 (C), 140.7 (C), 133.4 (CH), 132.2 (C),
131.2 (CH), 129.3 (2 × CH), 129.1 (2 × CH), 128.6 (2 × CH),
127.7 (2
× CH), 127.1 (C) ppm. HRMS (ESI) (m/z)
[C14H10D2O2S + H]+: calcd. 247.0762, found 247.0769.
Acknowledgements
We thank the Thailand Research Fund (TRF-BRG5880012), the
Center of Excellence for Innovation in Chemistry (PERCH-CIC),
the Office of the Higher Education Commission, Mahidol
University under the National Research Universities Initiative,
the Institute for the Promotion of Teaching Science and
Technology and Science achievement scholarship of Thailand,
and the Development and Promotion of Science and Technology
Talent Project (DPST) for financial support.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.

8
Tetrahedron
ACCEPTED MANUSCRIPT
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