Regioselective copper(I)-catalyzed C-H hydroxylation/C-S coupling: Expedient construction of 2-(styrylthio)phenols

Article abstract of DOI:10.1016/j.tet.2012.04.048

Regioselective copper(I)-catalyzed C-H hydroxylation/C-S coupling of aryl thiols with vinyl halides was developed. Starting from substituted aryl thiols and vinyl halides, various 2-(styrylthio)phenol derivatives were efficiently prepared. The application of the synthetic methodology to generate the bioactive organic intermediate was also exemplified.

Full text of DOI:10.1016/j.tet.2012.04.048

Tetrahedron 68 (2012) 5046e5052
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective copper(I)-catalyzed CeH hydroxylation/CeS coupling: expedient
construction of 2-(styrylthio)phenols
*
Run-Sheng Xu, Lei Yue, Yuan-Jiang Pan
Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Regioselective copper(I)-catalyzed CeH hydroxylation/CeS coupling of aryl thiols with vinyl halides was
developed. Starting from substituted aryl thiols and vinyl halides, various 2-(styrylthio)phenol de-
rivatives were efficiently prepared. The application of the synthetic methodology to generate the bio-
active organic intermediate was also exemplified.
Received 13 February 2012
Received in revised form 2 April 2012
Accepted 12 April 2012
Available online 21 April 2012
Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
Keywords:
Copper-catalyzed
Regioselective
CeH hydroxylation/CeS coupling
Aryl thiols
Vinyl halides
1. Introduction
copper(I)-catalyzed CeH hydroxylation/CeS coupling of aryl thiols
with various vinyl halides for the 2-(styrylthio)phenol derivatives
Organic sulfur compounds are ubiquitous in pharmaceuticals,
agrichemicals, and functionalized materials.1 In addition, as a soft
atom, sulfur has more activation pattern and higher coordination
ability. However, in comparison to the current state of the art in
carbon-,2 nitrogen-,3 and oxygen-4 directed CeH functionalization
reactions, sulfur-directed CeH functionalization reaction remains
underdeveloped in the past decades.5,6 The major handicap is that
the transition metal catalysts can be easily ‘poisoned’ by sulfur. It is
generally solved by oxidizing sulfur to sulfoxide or sulfone, because
sulfoxide and sulfone have a more moderate coordination ability.7
However, such manipulations will not only increase the reaction
steps but also limit the reagent diversity. Consequently, the de-
velopment of new strategies for sulfur-containing CeH function-
alizations is considered as a major challenge in modern organic
synthesis.
synthesis. We also exemplified this synthetic methodology to
generate the bioactive organic intermediate.
OMe
HO
S
OH
O
n(O)S
O
S
N
OH
O
O
HCl
HO
O
A potent ERαSERM
(E)-Styryl acetoxyphenylsulfides
Isovanillin-containing derivative
and sulfones
Scheme 1. Selected examples of 2-(styrylthio)phenols bioactive compounds.
2. Results and discussion
The 2-(styrylthio)phenol derivatives have been employed as key
intermediates in many bioactive compounds synthesis (Scheme 1).
However, some drawbacks, including numerous synthesis steps
and harsh reaction conditions exist in the previous synthetic
methods.8 Recently, our group reported an efficiently copper(I)-
catalyzed direct hydroxylation of arenes directed by an adjacent S
atom.9 Inspired by the results, herein, we reported a regioselective
Initially, the reaction of thiophenol (1a) with 1-((E)-2-iodovinyl)
benzene (2a) was chosen as the model reaction. Various
structurally similar enaminone ligands L1eL10 were investigated
(Scheme 2). The yield was observed increased by changing L1 to L5,
as well as L2 to L6. Additionally, other commercial viable ligands
such as 1,10-phenanthroline (L11) and N,N-dimethylethane-1,2-
diamine (L12) were observed ineffective. After analyzing the re-
sults, L5 was found as the best ligand (72% yield).
In order to further confirming the optimal condition, other pa-
rameters were optimized such as copper catalyst species, base
species, and reactant ratios (Table 1). Experimental results
* Corresponding author. Fax: þ86 571 87951629; e-mail addresses: pan-
yuanjiang@zju.edu.cn, cheyjpan@zju.edu.cn (Y.-J. Pan).
0040-4020/$ e see front matter Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.048

R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
5047
OH
the desired product 3a was formed in 78% yield when employed the
catalyst system L5 with CuI at 100 ꢀC (entry 11).
SH
O
I
S
CuI (20 mol%), L(20 mol%)
Cs2CO3 (2equiv), DMSO, N2
100oC
+
With the optimal condition in hand, we next investigated the
reaction scope, which was illustrated by substituted aryl thiols
with vinyl iodides in Table 2. Both meta- and para-substituted aryl
thiols were successfully transformed into the corresponding
products.
Next, we commenced investigating whether the vinyl bromides
were successfully endured in this methodology. To our delight, vi-
nyl bromides were also transformed to the corresponding products
in 55e83% yields (Table 3). It is worth noting that the multitude
substituent aryl thiols with vinyl bromides also gave the corre-
sponding product in 64e76% yields (entries 5ke5n), which dem-
onstrated that this methodology has a good tolerance of different
substrates aryl thiols.
1a
2a
3a
O
N
N
O
N
HN
R1
R2
OH
L1: R1 = H
L5: R2 = H
L6: R2 = CH3
L7: R2 = F
L2: R1 = CH3
L3: R1 = NO2
L10
O
HN
O
N
N
L11
R3
L8: R3 = H
NH HN
Furthermore, we turned our attention to the hetero-aromatic
vinyl halides (Table 4). To our delight, both 2-((E)-2-iodovinyl)
L9: R3 = OH
L4
L12
Table 2
Regioselective copper(I)-catalyzed CeH hydroxylation/CeS coupling of aryl thiols
with vinyl iodidesa
Scheme 2. Ligand performances in copper-catalyzed CeH hydroxylation/CeS coupling
reactions.
Table 1
Optimization of the model reactiona
OH
SH
I
S
Copper source, L (20 mol%)
Base (2equiv), DMSO, N2
+
1a
2a
3a
Entry
Copper source
Base
1a/2a
3ab [%]
1
2
3
4
5
6
7
8
Cu(SO3CF3)2
Cu(OAc)2
CuBr2
CuBr
CuI
CuI
CuI
CuI
CuI
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Na2CO3
K3PO4
MeONa
Cs2CO3
Cs2CO3
Cs2CO3
1:1
1:1
1:1
1:1
10
25
0
35
72
0
41
50
1:1
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
9
10
11
58c
75d
78(69e)
CuI
CuI
a
Unless otherwise noted, reactions conditions were 1a (0.5 mmol), copper source
(20 mol %), L5 (20 mol %), Cs2CO3 (2 equiv), protected by N2, in DMSO (3 mL), at
100 ꢀC for 24 h.
b
Isolated yield.
c
At 90 ꢀC.
d
At 110 ꢀC.
In air.
e
demonstrated that the copper(I) source gave a higher yield than the
copper(II) source (entries 1e4). In the presence of L5 with CuI, the
desired product 3a was formed in 72% yield (entry 5). Besides, re-
sults demonstrated that the reaction temperature was as an im-
portant parameter, which the desired product was formed in 58%
yield at 90 ꢀC (entry 9) and 75% yield at 110 ꢀC (entry 10). Finally,
a
Isolated yields for reactions conditions were 1 (0.5 mmol), 2 (0.6 mmol), CuI
(20 mol %), L5 (20 mol %), Cs2CO3 (2 equiv), protected by N2, in DMSO (3 mL), at
100 ꢀC for 24 h.

5048
R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
Table 3
thiophenes and 2-((E)-2-bromovinyl)thiophenes worked well in
this protocol. The corresponding products were isolated in 52e77%
yield. The stereochemistry of the 2-((E)-2-iodovinyl)thiophene and
2-((E)-2-bromovinyl)thiophenes was retained in the corresponding
product.
Regioselective copper(I)-catalyzed CeH hydroxylation/CeS coupling of aryl thiols
with vinyl bromidesa
The synthetic application of the regioselective copper(I)-cata-
lyzed CeH hydroxylation/CeS coupling reaction was exemplified
by the bioactive intermediate (E)-styryl-2-hydroxylphenyl sulfox-
ide synthesis which selective inhibition of COX-2 enzyme (COX
denote cyclooxygenases).8a The new strategy is very facile and
highly efficient (Scheme 3).
OH
O
S
I
SH
O
O
O
O
a)
b)
+
Br
Br
1t
2t
8 83%
a
Reagents and conditions: (i) 1t (1 mmol), 2t (1.2 mmol), CuI (20 mol %), L5 (20 mol
%), Cs2CO3 (2 equiv), protected by N2, in DMSO (3 mL), at 100 °C for 24 h. b (ii) 30%
H2O2 (2 mL), AcOH (1 equiv), 25 °C for 5 h.
Scheme 3. The synthetic application of the regioselective copper(I)-catalyzed CeH
hydroxylation/CeS coupling in (E)-styryl hydroxyphenyl sulfoxide synthesis.
In summary, a regioselective copper(I)-catalyzed CeH hydrox-
ylation/CeS coupling of aryl thiols with vinyl halides for the syn-
thesis of interesting building blocks 2-(styrylthio)phenol
derivatives was developed. The process is simple and efficient,
using inexpensive catalysts and under mild conditions. The appli-
cation of the synthetic methodology to generate the bioactive or-
ganic intermediate was very facile and highly efficient.
a
Isolated yields for reactions conditions were 1 (1 mmol), 4 (1.2 mmol), CuI
(20 mol %), L5 (20 mol %), Cs2CO3 (2 equiv), protected by N2, in DMSO (3 mL), at
100 ꢀC for 24 h.
3. Experimental section
3.1. General information
All reagents were obtained from commercial sources and used
without further purification. All NMR spectra were recorded on
AVANCE DMX-500 spectrometry at 500 MHz and 125 MHz for 1H
and 13C NMR in DMSO-d6, respectively. The NMR chemical shift
was reported in parts per million relative to 2.50 and 40.70 ppm
of DMSO as the standards of 1H and 13C NMR, respectively. Mass
Table 4
Regioselective copper(I)-catalyzed CeH hydroxylation/CeS coupling of aryl thiols
with 2-((E)-2-iodovinyl)thiophenea
OH
CuI (20 mol%), L5 (20 mol%)
Cs2CO3 (2 eq)
DMSO, 100 oC, 24 h, N2
S
SH
I
S
S
R1
R1
+
spectra were performed on
a 3000plus mass spectrometer
1
6
7
equipped with ESI interface and ion trap analyzer. The HRMS
were tested on 7-tesla FT-ICR MS equipped with an electrospray
source.
OH
OH
S
S
S
S
Cl
3.2. General procedure for preparation of L1eL710
7a, 65% (60%)[b]
OH
7b, 73% (71%)[b]
OH
Dimethylformamide
dimethylacetal
(DMFDMA)
(1.19 g,
10 mmol) and 1-(2-hydroxyphenyl) ethanone (1.36 g, 10 mmol)
were dissolved in p-xylene (2 mL). And the mixture was refluxed
for 12 h, then a yellow precipitate formation. The precipitate was
filtered out and washed with petroleum ether for three times. The
solid was dried under vacuum, and 1.79 g (94% yield) L5 was
obtained.
S
S
S
S
F3C
Br
7d, 75% (72%)[b]
OH
7c, 62% (52%)[b]
OH
S
S
S
S
3.3. General procedure for preparation of vinyl halides11
Cl
Cl
b
-Unsaturated carboxylic acid (1.48 g, 10 mmol) was added to
7e, 68%
7f, 77%
a solution of LiOAc (0.07 g, 1 mmol) in MeCN/H2O (97:3 v/v, 30 mL).
After the mixture was stirred for 5 min at room temperature, 1-
iodopyrrolidine-2,5-dione (2.25 g, 10 mmol) was added. Usual
workup by flash column chromatography on silica gel to afford the
1-((E)-2-bromovinyl)benzene 2a (1.36 g, 85%).
b2-(2-Bromoethenyl)thiophene.
Isolated yields for reactions conditions were 1 (0.5 mmol), 6 (0.6 mmol), CuI
(20 mol %), L5 (20 mol %), Cs2CO3 (2 equiv), protected by N2, in DMSO (3 mL) at
100 ꢀC for 24 h.
a

R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
5049
3.4. General procedure for synthesis of 2-(styrylthio)phenols
derivatives 3ae3w, 5ae5n, 7ae7f
156.6, 134.0, 132.5, 131.2, 130.1, 128.8, 122.2, 121.0, 11.3, 115.9, 115.3,
56.4. ESI-HRMS m/z: calcd for C15H12ClO2Sꢂ [MꢂH]ꢂ: 291.0252;
found 291.0246.
A mixture of thiophenols (0.5 mmol), 1-((E)-2-iodovinyl)ben-
zenes (0.6 mmol), CuI (19 mg, 20 mol %), L5 (19 mg, 20 mol %), and
Cs2CO3 (326 mg, 2 equiv) in DMSO (3 mL) was stirred in N2 at
100 ꢀC for 24 h., The mixture was quenched with saturated salt
water (10 mL) after the reaction completion. The solution was
extracted with ethyl acetate (3ꢁ10 mL). The organic layers were
combined and dried by sodium sulfate. The product 2-(styrylthio)
phenols was obtained by flash column chromatography on silica
gel.
3.4.8. 2-(4-Methoxystyrylthio)-5-(trifluoromethyl)phenol (3h). Yellow
liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.77 (s, 1H), 7.53 (d,
J¼8.5 Hz, 2H), 7.39 (d, J¼8.0 Hz, 1H), 7.17 (d, J¼8.5 Hz, 1H), 7.04e7.00
(m, 2H), 6.94e6.92 (m, 3H), 3.77(s, 3H); 13C NMR (125 MHz, DMSO-
d6):
d 160.5, 155.0, 136.6, 134.2, 129.9, 129.5, 129.2, 128.7, 117.5, 117.4,
116.1, 115.3, 111.7, 56.4. ESI-HRMS m/z: calcd for C16H12F3O2Sꢂ
[MꢂH]ꢂ: 325.0516; found 325.0508.
3.4.9. 2-(4-Methoxystyrylthio)-4-fluorophenol (3i). Colorless liquid;
3.4.1. 2-(Styrylthio)phenol (3a). Colorless liquid; 1H NMR
1H NMR (500 MHz, DMSO-d6):
d
9.98 (s, 1H), 7.51 (d, J¼8.5 Hz, 2H),
(500 MHz, DMSO-d6):
d
9.98 (s, 1H), 7.46 (d, J¼7.5 Hz, 2H),
7.04e6.98 (m, 2H), 6.92e6.90 (m, 2H), 6.90 (d, J¼8.0 Hz, 1H), 6.83
7.33e7.27 (m, 4H), 7.24 (d, J¼7.5 Hz, 1H), 7.13e7.09 (m, 2H), 6.90 (d,
(d, J¼8.5 Hz, 2H), 3.78 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
J¼8.0 Hz, 1H), 6.86 (t, J¼7.5 Hz, 1H), 6.68 (d, J¼15.5 Hz, 1H); 13C
d
160.3, 157.9, 156.1, 151.5, 135.2, 130.0, 129.0, 125.1, 118.4, 116.6,
NMR (125 MHz, DMSO-d6):
d
156.3, 137.5, 131.6, 131.3, 129.8, 129.3,
116.5, 115.3, 115.2, 115.0, 114.1, 114.0, 56.4. ESI-HRMS m/z: calcd for
128.5, 127.1, 124.1, 121.3, 121.1, 116.5. ESI-HRMS m/z: calcd for
C15H12FO2Sꢂ [MꢂH]ꢂ: 275.0548; found 275.0540.
C14H11OSꢂ [MꢂH]ꢂ: 227.0536; found 227.0530.
3.4.10. 2-(4-Methoxystyrylthio)-4-chlorophenol (3j). Colorless liq-
3.4.2. 5-Chloro-2-(styrylthio)phenol (3b). Colorless liquid; 1H NMR
uid; 1H NMR (500 MHz, DMSO-d6):
d
10.32 (s, 1H), 7.51 (d, J¼8.5 Hz,
(500 MHz, DMSO-d6):
d
10.58 (s, 1H), 7.48 (d, J¼7.5 Hz, 2H),
2H), 7.16 (s, 1H), 7.11 (d, J¼8.3 Hz, 1H), 7.01 (d, J¼15.5 Hz, 1H), 6.92
7.33e7.23 (m, 4H), 7.11 (d, J¼15.5 Hz, 1H), 6.92e6.89 (m, 2H), 6.72
(d, J¼8.5 Hz, 2H), 6.86e6.82 (m, 2H), 3.76 (s, 3H); 13C NMR
(d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d
158.1, 137.4,
(125 MHz, DMSO-d6): d 160.4, 154.2, 135.5, 130.0, 129.1, 127.9, 127.7,
133.1, 132.6, 132.2, 129.8, 128.7, 127.3, 123.2, 121.1, 121.0, 116.1. ESI-
HRMS m/z: calcd for C14H10ClOSꢂ [MꢂH]ꢂ: 261.0146; found
261.0138.
125.7, 124.5, 118.3, 117.3, 115.3, 56.4. ESI-HRMS m/z: calcd for
C15H12ClO2Sꢂ [MꢂH]ꢂ: 291.0252; found 291.0246.
3.4.11. 2-(4-Chlorostyrylthio)phenol (3k). Colorless liquid; 1H NMR
(500 MHz, DMSO-d6): d 10.02 (s, 1H), 7.54e7.48 (m, 2H), 7.37 (d,
3.4.3. 4-Chloro-2-(styrylthio)phenol (3c). Yellow liquid; 1H NMR
(500 MHz, DMSO-d6):
d
10.34 (s, 1H), 7.54 (d, J¼8.0 Hz, 2H),
J¼8.5 Hz, 2H), 7.30e7.28 (m, 1H), 7.19e7.13 (m, 2H), 6.90 (d,
7.35e7.32 (m, 2H), 7.27 (d, J¼7.3 Hz, 1H), 7.24 (d, J¼2.0 Hz, 1H), 7.21
(d, J¼15.5 Hz, 1H), 7.14 (d, J¼8.0 Hz, 1H), 6.89 (d, J¼8.5 Hz, 1H), 6.83
J¼8.0 Hz, 1H), 6.86e6.83 (m, 1H), 6.63 (d, J¼15.5 Hz, 1H); 13C NMR
(125 MHz, DMSO-d6): d 155.8, 135.8, 132.1, 130.8, 129.1, 129.1, 128.9,
(d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d
154.6, 137.3,
128.1, 126.7, 124.9, 120.4, 120.2, 115.8. ESI-HRMS m/z: calcd for
134.1, 131.8, 129.8, 128.9, 128.7, 128.3, 127.5, 124.7, 124.4, 122.1, 117.5.
ESI-HRMS m/z: calcd for C14H10ClOSꢂ [MꢂH]ꢂ: 261.0146; found
261.0139.
C14H10ClOSꢂ [MꢂH]ꢂ: 261.0146; found 261.0140.
3.4.12. 2-(4-Chlorostyrylthio)-5-bromophenol (3l). Colorless liquid;
1H NMR (500 MHz, DMSO-d6):
d
10.59 (s, 1H), 7.520 (d, J¼8.5 Hz,
3.4.4. 4-Bromo-2-(styrylthio)phenol (3d). Colorless liquid; 1H NMR
(500 MHz, DMSO-d6):
2H), 7.38 (d, J¼8.5 Hz, 2H), 7.24 (d, J¼8.0 Hz, 1H), 7.18 (d, J¼15.5Hz,
d
10.37 (s, 1H), 7.54 (d, J¼8.0 Hz, 2H),
1H), 7.05e7.01 (m, 2H), 6.71 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz,
7.42e7.33 (m, 3H), 7.29e7.24 (m, 2H), 7.21 (d, J¼15.5 Hz, 1H), 6.83
DMSO-d6): d 157.0, 136.2, 132.8, 132.4, 130.6, 129.6, 128.8, 124.2,
(m, 1H), 7.21 (d, J¼10.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
123.7, 121.2, 121.1, 118.8. ESI-HRMS m/z: calcd for C14H9BrClOSꢂ
[MꢂH]ꢂ: 338.9245; found 338.9240.
d
155.1, 137.3, 134.1, 131.5, 131.2, 129.8, 129.0, 127.5, 125.1, 122.1,
118.0, 111.9. ESI-HRMS m/z: calcd for C14H10BrOSꢂ [MꢂH]ꢂ:
304.9715; found 304.9714.
3.4.13. 2-(4-Chlorostyrylthio)-5-(trifluoromethyl)phenol (3m). Color-
less liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.84 (s, 1H), 7.59 (d,
3.4.5. 3-Chloro-2-(styrylthio)phenol (3e). Colorless liquid; 1H NMR
(500 MHz, DMSO-d6):
J¼8.5 Hz, 2H), 7.47 (d, J¼8.0 Hz, 1H), 7.41 (d, J¼8.0 Hz, 2H), 7.30 (d,
d
10.46 (s, 1H), 7.31 (d, J¼2.0 Hz, 2H),
J¼15.5 Hz, 1H), 7.18 (d, J¼8.0 Hz, 1H), 7.10 (s, 1H), 6.93 (d,
7.28e7.24 (m, 3H), 7.17 (d, J¼7.6 Hz, 1H), 7.08 (d, J¼8.0 Hz, 1H),
J¼15.0 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 155.4, 136.2,
6.97e6.94 (m, 2H), 6.20 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz,
133.5, 129.9, 129.7, 129.3, 128.7, 128.6, 122.6, 117.5, 111.9. ESI-
HRMS m/z: calcd for C15H10ClF3OSꢂ [MꢂH]ꢂ: 330.0016; found
330.0012.
DMSO-d6):
d 161.1, 139.8, 137.6, 132.5, 129.8, 128.0, 126.8, 126.7,
125.7, 121.7, 117.2, 116.1. ESI-HRMS m/z: calcd for C14H10ClOSꢂ
[MꢂH]ꢂ: 261.0146; found 261.0139.
3.4.14. 2-(4-Chlorostyrylthio)-4-fluorophenol (3n). Colorless liquid;
3.4.6. 2-(4-Methoxystyrylthio)phenol (3f). Colorless liquid; 1H NMR
1H NMR (500 MHz, DMSO-d6):
d
10.04 (s, 1H), 7.57 (d, J¼8.0 Hz, 2H),
(500 MHz, DMSO-d6):
d
9.96 (s, 1H), 7.43 (d, J¼8.5 Hz, 2H), 7.23 (d,
7.40 (d, J¼8.0 Hz, 2H), 7.27 (d, J¼15.5 Hz, 1H), 7.14e7.12 (m, 1H),
6.93e6.91 (m, 1H), 6.85 (d, J¼8.5 Hz, 1H), 6.81 (d, J¼15.5 Hz, 1H);
J¼8.0 Hz, 1H), 7.11 (d, J¼7.5 Hz, 1H), 6.93e6.81 (m, 5H), 6.70 (d,
J¼15.5 Hz, 1H), 3.74 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
d
159.9,
13C NMR (125 MHz, DMSO-d6):
d 157.7, 155.8, 151.8, 136.1, 133.0,
155.7, 134.0, 132.7, 130.2, 129.3, 128.6, 128.5, 127.8, 122.2, 120.9,
120.2, 116.1, 115.1, 56.2. ESI-HRMS m/z: calcd for C15H13O2Sꢂ
[MꢂH]ꢂ: 257.0639; found 257.0635.
131.6, 129.6, 129.0, 123.5, 116.6, 116.5, 115.9, 115.7, 114.7, 114.6. ESI-
HRMS m/z: calcd for C14H9ClFOSꢂ [MꢂH]ꢂ: 279.0052; found
279.0047.
3.4.7. 2-(4-Methoxystyrylthio)-5-chlorophenol (3g). Pale yellow
3.4.15. 2-(4-Chlorostyrylthio)-4-bromophenol (3o). Colorless liquid;
liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.55 (s, 1H), 7.45 (d,
1H NMR (500 MHz, DMSO-d6):
d
10.42 (s, 1H), 7.57 (d, J¼7.5 Hz, 2H),
J¼7.5 Hz, 2H), 7.23 (d, J¼8.0 Hz, 2H), 6.92e6.89 (m, 5H), 6.75 (d,
7.39e7.35 (m, 2H), 7.27e7.24 (m, 2H), 6.84 (d, J¼9.0 Hz, 1H), 6.79 (d,
J¼15.5 Hz, 1H), 3.75 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
d
160.2,
J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 155.0, 136.1, 133.1,

5050
R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
131.9, 131.5, 131.2, 129.7, 129.0, 124.5, 123.4, 117.9, 111.7. ESI-HRMS
6.80e6.77 (m, 2H), 6.72 (d, J¼8.0 Hz, 1H), 6.17 (d, J¼15.5 Hz, 1H),
5.98 (s, 2H); 13C NMR (125 MHz, DMSO-d6):
161.1, 149.0, 147.5,
139.7, 132.3, 132.2, 127.3, 123.4, 121.7, 121.5, 117.6, 116.1, 109.4, 106.1,
102.1. ESI-HRMS m/z: calcd for C15H10ClO3Sꢂ [MꢂH]ꢂ: 305.0045;
found 305.0050.
m/z: calcd for C14H10BrClOS [MꢂH]ꢂ: 338.9330; found 338.9324.
d
3.4.16. 2-(3-Chlorostyrylthio)-5-bromophenol (3p). Colorless liquid;
1H NMR (500 MHz, DMSO-d6):
d 10.61 (s, 1H), 7.62 (s, 1H), 7.45 (d,
J¼8.0 Hz, 1H), 7.35 (d, J¼8.5 Hz, 1H), 7.29e7.25 (m, 3H), 7.07e7.02
(m, 2H), 6.68 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
3.4.24. 5-Bromo-2-(styrylthio)phenol (5a). Pale yellow liquid; 1H
d
157.3, 139.6, 134.7, 132.8, 131.6, 130.2, 128.2, 126.7, 126.0, 125.7,
NMR (500 MHz, DMSO-d6):
d
10.57 (s, 1H), 7.49 (d, J¼7.5 Hz, 2H),
123.8, 121.5, 121.0, 119.0. ESI-HRMS m/z: calcd for C14H9BrClOSꢂ
[MꢂH]ꢂ: 338.9330; found 338.9324.
7.34e7.31 (m, 2H), 7.25 (d, J¼7.5 Hz, 2H), 7.12 (d, J¼15.5 Hz, 1H),
7.05e7.02 (m, 2H), 6.74 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz,
DMSO-d6):
d 157.1, 137.4, 132.9, 132.3, 129.8, 128.8, 127.3, 123.8,
3.4.17. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)phenol(3q). Color-
122.9, 121.8, 121.2, 118.9. ESI-HRMS m/z: calcd for C14H10BrOSꢂ
[MꢂH]ꢂ: 304.9715; found 304.9710.
less liquid; 1H NMR (500 MHz, DMSO-d6):
d 9.96 (s, 1H), 7.25 (d,
J¼7.7 Hz, 2H), 7.11e7.08 (m, 1H), 6.98 (d, J¼15.5 Hz, 1H), 6.89e6.8 (m,
4H), 6.67 (d, J¼15.5 Hz, 1H), 6.01 (s, 2H); 13C NMR (125 MHz, DMSO-
3.4.25. 5-(Trifluoromethyl)-2-(styrylthio)phenol (5b). Pale yellow
d6):
d
155.9, 149.0, 148.0, 134.2, 132.7 132.1, 130.5, 130.2, 128.8, 128.7,
liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.79 (s, 1H), 7.56 (d,
122.2 122.1, 121.2, 121.1, 116.3, 109.5, 106.6, 102.2. ESI-HRMS m/z: calcd
J¼7.5 Hz, 2H), 7.45 (d, J¼8.0 Hz, 1H), 7.37 (d, J¼7.5 Hz, 2H), 7.29 (d,
for C15H11O3S [MꢂH]ꢂ: 271.0434; found 271.0426.
J¼7.5 Hz, 1H), 7.23 (d, J¼15.5 Hz, 1H), 7.18 (d, J¼8.0 Hz, 1H), 7.11 (s,
1H), 6.96 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 154.8,
3.4.18. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-5-ethylphenol
136.6, 134.9, 129.3, 128.8, 128.6, 128.5, 128.0, 127.7, 127.0, 125.8,
123.7, 120.6, 116.9, 111.2. ESI-HRMS m/z: calcd for C15H10F3OSꢂ
[MꢂH]ꢂ: 295.0486; found 295.0480.
(3r). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 9.83 (s, 1H),
7.18e7.16 (m, 2H), 6.93 (d, J¼15.0 Hz, 1H), 6.84 (s, 2H), 6.73 (s, 2H),
6.70 (d, J¼8.0 Hz, 1H), 6.68 (d, J¼15.5 Hz, 1H), 6.00 (s, 2H),
2.54e2.49 (m, 2H), 1.16e1.13 (m, 3H); 13C NMR (125 MHz, DMSO-
3.4.26. 2-(4-Methoxystyrylthio)-5-bromophenol (5c). Pale yellow
d6):
d
156.4, 149.0,147.9, 145.4, 132.2, 131.5, 131.3, 122.3, 122.0, 120.7,
liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.52 (s, 1H), 7.46 (d,
118.3, 115.9, 109.5, 106.5, 102.2, 19.0, 16.7. ESI-HRMS m/z: calcd for
J¼8.5 Hz, 2H), 7.17 (d, J¼8.5 Hz, 1H), 7.02 (d, J¼5.5 Hz, 2H),
C17H15O3Sꢂ [MꢂH]ꢂ: 299.0747; found 299.0740.
6.92e6.89 (m, 3H), 6.77 (d, J¼15.0 Hz, 1H), 3.77(s, 3H); 13C NMR
(125 MHz, DMSO-d6): d 160.2, 156.6, 134.2, 131.4, 130.1, 128.9, 123.8,
3.4.19. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-5-chlorophenol
122.8, 120.5, 119.1, 118.7, 115.3. ESI-HRMS m/z: calcd for
(3s). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.51 (s, 1H),
C15H12BrO2Sꢂ [MꢂH]ꢂ: 334.9747; found 334.9739.
7.25 (d, J¼8.0 Hz, 2H), 6.97 (d, J¼15.5 Hz, 1H), 6.90e6.88 (m, 3H),
6.86 (d, J¼8.0 Hz, 1H), 6.71 (d, J¼15.5 Hz, 1H), 6.01 (s, 2H); 13C NMR
3.4.27. 2-(4-Methoxystyrylthio)-4-bromophenol (5d). Colorless liq-
(125 MHz, DMSO-d6):
d
156.4, 148.8, 147.9, 133.5, 132.3, 131.7, 131.1,
uid; 1H NMR (500 MHz, DMSO-d6):
d
10.35 (s, 1H), 7.50 (d, J¼8.5 Hz,
122.2, 121.7, 120.7, 120.0, 115.7, 109.2, 106.4, 102.1. ESI-HRMS m/z:
2H), 7.26 (s, 1H), 7.23e7.21 (m, 1H), 7.00 (d, J¼15.5 Hz, 1H), 6.92 (d,
calcd for C15H10ClO3Sꢂ [MꢂH]ꢂ: 305.0045; found 305.0037.
J¼8.5 Hz, 2H), 6.84e6.80 (m, 2H), 3.73 (s, 3H); 13C NMR (125 MHz,
DMSO-d6):
d 160.4, 154.7, 135.6, 130.7, 130.0, 129.1, 126.2, 118.3,
3.4.20. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-5-bromophenol
117.9, 115.3, 111.9, 56.4. ESI-HRMS m/z: calcd for C15H12BrO2Sꢂ
[MꢂH]ꢂ: 334.9747; found 334.9741.
(3t). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.49 (s, 1H),
7.24 (m, 1H), 7.24 (d, J¼17.0 Hz, 1H), 7.02e7.00 (m, 2H), 6.96 (d,
J¼15.5 Hz, 1H), 6.91 (d, J¼8.0 Hz, 1H), 6.87 (d, J¼8.0 Hz, 1H), 6.72 (d,
3.4.28. 2-(4-Chlorostyrylthio)-5-fluorophenol (5e). Colorless liquid;
J¼15.5 Hz, 1H), 6.01 (s, 2H); 13C NMR (125 MHz, DMSO-d6):
d
156.4,
1H NMR (500 MHz, DMSO-d6):
d
10.57 (s, 1H), 7.46 (d, J¼8.5 Hz, 2H),
148.8,148.0,133.7,131.7,131.3,123.6,122.4,122.2,120.4,119.8,118.5,
109.3, 106.5, 102.1. ESI-HRMS m/z: calcd for C15H10BrO3Sꢂ [MꢂH]ꢂ:
348.9612; found 348.9608.
7.36e7.33 (m, 3H), 7.13 (d, J¼15.5 Hz, 1H), 6.73e6.69 (m, 2H), 6.51
(d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 164.7, 162.7,
158.6, 158.5, 136.5, 134.4, 134.3, 132.6, 129.7, 128.7, 128.6, 126.1,
116.0, 108.0, 107.9, 104.1, 103.9. ESI-HRMS m/z: calcd for
C14H9ClFOSꢂ [MꢂH]ꢂ: 279.0125; found 279.0120.
3.4.21. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-4-chlorophenol
(3u). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.32 (s,
1H), 7.32 (s, 1H), 7.18 (d, J¼2.0 Hz, 1H), 7.10 (d, J¼8.5 Hz, 1H), 7.06 (d,
3.4.29. 2-(4-Chlorostyrylthio)-5-chlorophenol (5f). Colorless liquid;
J¼15.5 Hz, 1H), 6.95e6.93 (m, 1H), 6.88e6.83 (m, 2H), 6.80 (d,
1H NMR (500 MHz, DMSO-d6):
d
10.59 (s, 1H), 7.51 (d, J¼8.5 Hz, 2H),
J¼15.5 Hz, 1H), 6.02 (s, 2H); 13C NMR (125 MHz, DMSO-d6):
d
154.2,
7.37 (d, J¼8.5 Hz, 2H), 7.31 (d, J¼8.0 Hz, 1H), 6.18 (d, J¼15.5 Hz, 1H),
149.0, 148.4, 135.2, 131.8, 127.4, 127.0, 125.5, 124., 122.8, 119.1, 117.3,
109.5, 106.8, 102.3. ESI-HRMS m/z: calcd for C15H10ClO3Sꢂ [MꢂH]ꢂ:
305.0045; found 305.0037.
6.91e6.89 (m, 2H), 6.68 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz,
DMSO-d6):
d 157.2, 136.4, 133.3, 133.0, 132.5, 130.6, 129.8, 128.9,
124.6, 121.0, 120.6, 116.2. ESI-HRMS m/z: calcd for C14H9Cl2OSꢂ
[MꢂH]ꢂ: 294.9829; found 294.9822.
3.4.22. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-4-bromophenol
(3v). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.34 (s,
3.4.30. 2-(4-Chlorostyrylthio)-4-chlorophenol (5g). Colorless liquid;
1H), 7.31 (d, J¼1.5 Hz, 1H), 7.28 (d, J¼2.0 Hz, 1H), 7.22 (d, J¼8.5 Hz,
1H), 7.05 (d, J¼15.5 Hz, 1H), 6.97e6.93 (m, 1H), 6.87 (d, J¼8.0 Hz,
1H), 6.81 (d, J¼15.5 Hz, 1H), 6.02 (s, 2H); 13C NMR (125 MHz,
1H NMR (500 MHz, DMSO-d6):
d
10.38 (s,1H), 7.57 (d, J¼8.5 Hz, 2H),
7.39e7.38 (m, 2H), 7.28e7.25 (m, 2H), 7.15e7.13 (m, 1H), 6.89e6.86
(m, 1H), 6.80 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
DMSO-d6):
d
154.7, 149.0, 148.4, 135.2, 131.8, 130.7, 126.0, 124.2,
d 154.7, 136.3, 133.2, 132.1, 131.5, 129.8, 129.7, 129.2, 128.9, 128.5,
122.8, 119.1, 117.9, 111.9, 109.5, 106.8, 102.3. ESI-HRMS m/z: calcd for
124.4, 124.2, 123.6, 117.5. ESI-HRMS m/z: calcd for C14H9Cl2OSꢂ
[MꢂH]ꢂ: 294.9829; found 294.9822.
C15H10BrO3Sꢂ [MꢂH]ꢂ: 348.9504; found 348.9532.
3.4.23. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-3-chlorophenol
3.4.31. 2-(4-Bromophenylthio)-5-methylphenol (5h). Colorless liq-
(3w). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.41 (s,
uid; 1H NMR (500 MHz, DMSO-d6):
d
9.90 (s, 1H), 7.45 (d, J¼8.3 Hz,
1H), 7.28e7.24 (m, 1H), 7.06 (d, J¼6.0 Hz, 2H), 6.95 (d, J¼8.0 Hz, 1H),
2H), 7.19 (d, J¼7.8 Hz, 1H), 6.99 (d, J¼8.3 Hz, 2H), 6.78 (s, 1H), 6.68

R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
5051
(d, J¼7.8 Hz, 1H), 2.25 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
1H), 6.92e6.88 (m, 2H), 6.88 (d, J¼12.5 Hz, 1H), 6.78 (d, J¼15.0 Hz,
1H); 13C NMR (125 MHz, DMSO-d6):
157.2, 141.9, 133.3, 132.4, 131.5,
130.6, 129.0, 127.0, 126.5, 126.4, 121.7, 121.0, 120.7, 116.2. ESI-HRMS m/
z: calcd for C12H8ClOSꢂ2 [MꢂH]ꢂ: 266.9783; found 266.9776.
d
158.87, 142.18, 138.29, 136.68, 132.93, 130.08, 122.17, 119.31, 117.93,
d
114.57, 22.15. ESI-HRMS m/z: calcd for C16H13O3Sꢂ [MꢂH]ꢂ:
285.0590; found 285.0583.
3.4.32. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-5-fluorophenol
3.4.40. 2-((E)-2-(Thiophen-2-yl)vinylthio)-5-bromophenol
(5i). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.49 (s, 1H),
(7c). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.60 (s,1H),
7.30 (d, J¼8.0 Hz, 2H), 7.18 (s, 1H), 6.92 (d, J¼15.5 Hz, 1H), 6.84 (s,
7.44 (d, J¼5.0 Hz, 1H), 7.18 (d, J¼9.0 Hz, 1H), 7.13 (d, J¼3.0 Hz, 1H),
2H), 6.71e6.67 (m, 2H), 6.56 (d, J¼15.0 Hz, 1H), 6.00 (s, 2H); 13C
7.06e7.01 (m, 3H), 6.90e6.87 (d, J¼10.5 Hz, 1H), 6.78 (d, J¼15.5 Hz,
NMR (125 MHz, DMSO-d6):
d
164.1, 162.1, 157.8, 157.7, 148.8, 147.7,
1H); 13C NMR (125 MHz, DMSO-d6):
d 157.2, 141.9, 132.5, 129.0,
132.9, 132.9, 131.8, 131.5, 121.8, 121.6, 117.1, 109.2, 107.7, 107.5, 106.3,
103.7, 103.5, 102.0. ESI-HRMS m/z: calcd for C15H10FO3Sꢂ [MꢂH]ꢂ:
289.0340; found 289.0333.
127.1, 126.6, 123.9, 121.5, 121.4, 119.0. ESI-HRMS m/z: calcd for
C12H8BrOSꢂ2 [MꢂH]ꢂ: 310.9278; found 310.9271.
3.4.41. 2-((E)-2-(Thiophen-2-yl)vinylthio)-5-(trifluoromethyl)phenol
3.4.33. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-5-(tri-
(7d). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.83 (s,
fluoromethyl)phenol (5j). Colorless liquid; 1H NMR (500 MHz,
1H), 7.49 (d, J¼5.0 Hz, 1H), 7.39 (d, J¼8.5 Hz, 1H), 7.22 (d, J¼3.0 Hz,
DMSO-d6):
d
10.76 (s, 1H), 7.41 (d, J¼8.0 Hz, 1H), 7.32 (d, J¼2.0 Hz,
1H), 7.18 (d, J¼8.0 Hz, 1H), 7.13e7.19 (m, 2H), 7.06 (d, J¼8.0 Hz, 1H),
1H), 7.16 (d, J¼8.0 Hz, 1H), 7.09e7.04 (m, H), 6.98e6.96 (m, 1H),
6.89 (d, J¼15.0 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 155.3,
6.90e6.87 (m, 2H), 6.03 (s, 2H); 13C NMR (125 MHz, DMSO-d6):
141.6, 130.6, 129.4, 129.1, 128.9, 128.7, 128.4, 128.3, 127.8, 127.2,
126.4, 124.2, 119.5, 117.6, 111.9. ESI-HRMS m/z: calcd for C13H8F3OS2ꢂ
[MꢂH]ꢂ: 301.0047; found 301.0040.
d
155.0, 149.1, 148.5, 136.3, 131.7, 129.7, 128.8, 128.6, 128.2, 127.9,
126.5, 124.3, 122.9, 118.3, 117.5, 111.7, 109.5, 106.9, 102.4. ESI-HRMS
m/z: calcd for C16H10F3O3Sꢂ [MꢂH]ꢂ: 339.0308; found 339.0299.
3.4.42. 2-((E)-2-(Thiophen-2-yl)vinylthio)-4-chlorophenol
3.4.34. 4,5-Dichloro-2-(styrylthio)phenol (5k). Pale yellow liquid;
(7e). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.38 (s,1H),
1H NMR (500 MHz, DMSO-d6):
d
10.85 (s, 1H), 7.55 (d, J¼7.5 Hz, 2H),
7.46 (d, J¼5.0 Hz, 1H), 7.18e7.15 (m, 3H), 7.14 (d, J¼2.0 Hz, 1H), 7.04
7.41 (s,1H), 7.36e7.33 (m, 2H), 7.28e7.25 (m,1H), 7.23 (d, J¼15.5 Hz,
(d, J¼8.5 Hz, 1H), 6.99 (d, J¼15.5 Hz, 1H), 6.88 (d, J¼13.5 Hz, 1H),
1H), 7.04 (s, 1H), 6.86 (d, J¼15.5 Hz,1H); 13C NMR (125 MHz, DMSO-
6.86 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 154.8,
d6):
d
155.0,137.0,134.5,129.9,129.7,128.9,127.5,124.2,122.4,121.3,
141.7, 129.1, 129.0, 128.6, 127.9, 127.4, 126.9, 124.4, 120.7, 117.6. ESI-
HRMS m/z: calcd for C12H8ClOSꢂ2 [MꢂH]ꢂ: 266.9783; found
266.9776.
117.1. ESI-HRMS m/z: calcd for C14H9Cl2OSꢂ [MꢂH]ꢂ: 294.9829;
found 294.9822.
3.4.35. 2-(4-Methoxystyrylthio)-4,5-dichlorophenol (5l). Colorless
3.4.43. 2-((E)-2-(Thiophen-2-yl)vinylthio)-3-chlorophenol
liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.80 (s, 1H), 7.50 (d,
(7f). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.51 (s, 1H),
J¼8.5 Hz, 2H), 7.32 (s, 1H), 7.02e6.98 (m, 2H), 6.92 (d, J¼8.5 Hz, 1H),
7.34 (d, J¼3.0 Hz, 1H), 7.30e7.26 (m, 1H), 7.07 (d, J¼8.0 Hz, 1H), 6.96
6.86 (d, J¼15.0 Hz, 1H), 3.76 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
(d, J¼8.5 Hz, 3H), 6.68 (d, J¼15.0 Hz, 1H), 6.37e6.34 (d, J¼15.0 Hz,
d
160.5, 154.8, 136.0, 131.3, 129.9, 129.6, 129.3, 129.2, 125.4, 122.6,
1H); 13C NMR (125 MHz, DMSO-d6):
d 161.1, 142.3, 139.7, 132.6,
117.7, 117.1, 115.3, 115.1, 56.4. ESI-HRMS m/z: calcd for C15H11Cl2O2Sꢂ
[MꢂH]ꢂ: 324.9862; found 324.9853.
128.9, 125.8, 125.5, 124.4, 121.8, 120.9, 116.9, 116.2. ESI-HRMS m/z:
calcd for C12H8ClOSꢂ2 [MꢂH]ꢂ: 266.9783; found 266.9776.
3.4.36. 2-(4-Chlorostyrylthio)-4,5-dichlorophenol (5m). Colorless liq-
3.4.44. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylsulfinyl)-5-
bromophenol (8). A mixture of 2-((E)-2-(benzo[d][1,3]dioxol-5-yl)
vinylthio)-5-bromophenol 3t (175 mg, 0.5 mmol), AcOH (44 mg,
0.5 mmol), and 30% H2O2 (2 mL) was stirred in air at 25 ꢀC for 5 h.
After completion of the reaction, the mixture was quenched with
saturated salt water (10 mL) and the solution was extracted with
ethyl acetate (3ꢁ10 mL). The organic layers were combined, and
dried over sodium sulfate. The pure product was obtained by flash
column chromatography on silica gel to afford 8 (174 mg, 95%
yield). The spectroscopic data of all the products are presented
uid; 1H NMR (500 MHz, DMSO-d6):
d
10.86 (s, 1H), 7.57 (d, J¼8.5 Hz,
2H), 7.44 (s,1H), 7.39 (d, J¼8.0 Hz, 2H), 7.28 (d, J¼15.5 Hz,1H), 7.04 (s,
1H), 6.82 (d, J¼15.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
d 155.3,
136.2, 133.3, 132.5, 131.5, 130.5, 129.8, 129.7, 129.3, 125.6, 123.8, 123.0,
122.6, 117.3. ESI-HRMS m/z: calcd for C14H8Cl3OSꢂ [MꢂH]ꢂ:
328.9367; found 328.9376.
3.4.37. 2-((E)-2-(Benzo[d][1,3]dioxol-5-yl)vinylthio)-4,5-dichlorophenol
(5n). Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 10.81 (s, 1H),
7.36 (d, J¼15.5 Hz, 2H), 7.07e7.01 (m, 2H), 6.96 (d, J¼8.0 Hz, 1H), 6.89
below. Colorless liquid; 1H NMR (500 MHz, DMSO-d6):
d 11.11 (s,
(d, J¼8.0 Hz, 1H), 6.83 (d, J¼15.0 Hz, 1H), 6.03 (s, 2H); 13C NMR
1H), 7.68 (s, 1H), 7.47 (d, J¼8.5 Hz, 1H), 7.30 (d, J¼12.0 Hz, 1H), 7.25
(125 MHz, DMSO-d6):
d 154.7, 149.0, 148.5, 135.7, 131.7, 129.6, 129.3,
(d, J¼6.0 Hz, 2H), 7.22 (d, J¼1.5 Hz, 2H), 6.92 (d, J¼9.0 Hz, 1H), 6.07
125.2, 123.0, 122.6, 118.5, 117.1, 109.5, 106.9, 102.4. ESI-HRMS m/z: calcd
(d, J¼18.5 Hz, 2H); 13C NMR (125 MHz, DMSO-d6):
d 156.0, 149.7,
for C15H9Cl2O3Sꢂ [MꢂH]ꢂ: 338.9728; found 338.9721.
149.2, 136.0, 130.8, 129.4, 127.1, 125.7, 125.0, 124.1, 119.6, 109.6,
108.0, 102.6. ESI-HRMS m/z: calcd for C15H10BrO4Sꢂ [MꢂH]ꢂ:
364.9561; found 364.9554.
3.4.38. 2-((E)-2-(Thiophen-2-yl)vinylthio)phenol (7a). Colorless liq-
uid; 1H NMR (500 MHz, DMSO-d6):
d 10.04 (s,1H), 7.47e7.41 (m, 2H),
7.41 (d, J¼2.5 Hz, 1H), 7.31 (d, J¼3.5 Hz, 1H), 6.89 (d, J¼8.0 Hz, 1H),
Acknowledgements
7.02 (d, J¼8.5 Hz, 1H), 6.90e6.83 (m, 2H), 6.80 (d, J¼6.0 Hz, 1H); 13C
NMR (125 MHz, DMSO-d6):
d
156.5, 142.1, 131.6, 130.7, 130.1, 129.7,
The authors are grateful to the National Natural Science Foun-
dation of China (Nos. 21025207, 20975092).
129.0, 126.6, 126.2, 125.3, 122.9, 121.2, 120.9, 116.6. ESI-HRMS m/z:
calcd for C12H9OSꢂ2 [MꢂH]ꢂ: 233.0173; found 233.0166.
Supplementary data
3.4.39. 2-((E)-2-(Thiophen-2-yl)vinylthio)-5-chlorophenol (7b). Color-
less liquid; 1H NMR (500 MHz, DMSO-d6):
d
10.60 (s, 1H), 7.48e7.42
These data include 1H and 13C NMR spectra of the most im-
portant compounds described in this article. Supplementary data
(m, 2H), 7.25 (d, J¼8.5 Hz, 1H), 7.12 (d, J¼2.0 Hz, 1H), 7.03e7.00 (m,

5052
R.-S. Xu et al. / Tetrahedron 68 (2012) 5046e5052
6452e6455; (k) Yeung, C. S.; Zhao, X.; Borduas, N.; Dong, V. M. Chem. Sci. 2010,
1, 331e336.
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2012.04.048.
4. For oxygen-containing group in directed CeH activations, see: (a) Terao, Y.;
Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2001, 123,
10407e10408; (b) Wang, D.-H.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130,
17676e17677; (c) Neufeldt, S. R.; Sanford, M. S. Org. Lett. 2010, 12, 532e535; (d)
Lu, Y.; Wang, D.-H.; Engle, K. M.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132,
5916e5921.
5. For reviews, see: (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147e1169; (b) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42,
1074e1086; (c) Giri, R.; Shi, B.-F.; Engle, K.; Maugel, M. N.; Yu, J.-Q. Chem. Soc.
Rev. 2009, 38, 3242e3272.
6. For sulfur-containing group in directed CeH activations: (a) Coulter, M. M.; Kou,
K. G.; Galligan, M. B.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 16330e16333; (b)
Richter, H.; Beckendorf, S.; Mancheno, O. G. Adv. Synth. Catal. 2011, 353,
295e302.
7. Alfonso, G.-R. M.; Angeles, F.-I.; Ramon, G. A.; Juan, C. C. Chem.dEur. J. 2011, 17,
356e368.
8. For examples of recent work, see: (a) Ramana Reddy, M. V.; Mallireddigari, M.
R.; Pallela, V. R.; Venkatapuram, P.; Boominathan, R. S.; Bell, C.; Reddy, E. P. Med.
Bioorg. Chem. 2005, 13, 1715e1723; (b) Song, Z. J.; King, A. O.; Waters, M. S.;
Lang, F. R.; Zewge, D.; Bio, M.; Leazer, J. L., Jr.; Javadi, G.; Kassim, A.; Tschaen, D.
M.; Reamer, R.; Rosner, A. T.; Chilenski, J. R. D.; Mathre, J.; Volante, R.; Tillyer, P.
R. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5776e5781; (c) Capozzi, F. G.; Me-
nichetti, C. S.; Nativi, C. J. Org. Chem. 1997, 62, 2611e2615.
References and notes
1. For examples of recent work, see: (a) Mellah, M.; Voituriez, A.; Schulz, E. Chem.
Rev. 2007, 107, 5133e5209; (b) Hiroi, K.; Sone, T. Curr. Org. Synth. 2008, 5,
305e320; (c) Arunakaran, J.; Arunkumar, A.; Vijayababu, M.; Venkataraman, P.;
Senthilkumar, K. Biol. Pharm. Bull. 2006, 29, 375e379; (d) Shukla, Y.; Arora, A.;
Siddiqui, I. Mol. Cancer Ther. 2004, 3, 1459e1466; (e) Block, E.; Cai, X.-J.; Uden,
P. C.; Zhang, X.; Quimby, B. D.; Sullivan, J. J. Pure Appl. Chem. 1996, 68, 937e944;
(f) Nenajdenko, V. G.; Krasovskiy, A. L.; Balenkova, E. S. Tetrahedron 2007, 63,
12481e12539.
2. For carbon-containing group in directed CeH activations, see: (a) Giri, R.;
Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am.
Chem. Soc. 2007, 129, 3510e3511; (b) Nakano, M.; Tsurugi, H.; Satoh, T.; Miura,
M. Org. Lett. 2008, 10, 1851e1854; (c) Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q.
Angew. Chem., Int. Ed. 2008, 47, 5215e5219; (d) Wang, D.-H.; Engle, K. M.; Shi,
B.-F.; Yu, J.-Q. Science 2009, 327, 315e319; (e) Dubost, E.; Fossey, C.; Cailly, T.;
Rault, S.; Fabis, F. J. Org. Chem. 2011, 76, 6414e6420.
3. For nitrogen-containing group in directed CeH activations, see: (a) Miura, M.;
Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211e5215;
(b) Boele, M. D. K.; Strijdonck, G. P. F.; Vries, A. H. M.; Kamer, P. C. J.; Vries, J. G.
P.; Leewen, W. N. M. J. Am. Chem. Soc. 2002, 124, 1586e1587; (c) Shi, Z.; Zhang,
C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed. 2009, 48,
4572e4576; (d) Ueda, S.; Okada, T.; Nagasawa, H. Chem. Commun. 2010,
2462e2464; (e) Nishikata, T.; Lipshutz, B. H. Org. Lett. 2010, 12, 1972e1975; (f)
Cho, S. H.; Hwang, S.; Chang, J. S. J. Am. Chem. Soc. 2008, 130, 9254e9256; (g)
Nakao, Y.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 2448e2449; (h)
Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem. Soc. 2009, 131,
13888e13889; (i) Cai, G.; Fu, Y.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129,
7666e7673; (j) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47,
9. Xu, R. S.; Wan, J.-P.; Mao, H.; Pan, Y. J. Am. Chem. Soc. 2010, 132,
15531e15533.
10. (a) Al-Saleh, B.; El-Apasery, M. A.; Abdel-Aziz, R. S.; Elnagdi, M. H. J. Heterocycl.
Chem. 2005, 42, 563e566; (b) Kantevari, S.; Chary, M. V.; Vuppalapati, S. V. N.
Tetrahedron 2007, 63, 13024e13031; (c) Vasselin, D. A.; Westwell, A. D.; Mat-
thews, C. S. T.; Bradshaw, D.; Stevens, M. F. G. J. Med. Chem. 2006, 49,
3973e3981.
11. Chowdhury, S.; Roy, S. J. Org. Chem. 1997, 62, 199e200.