Synthesis of 2-selenyl(sulfenyl)benzofurans via Cu-catalyzed tandem reactions of 2-(gem-dibromovinyl)phenols with diorganyl diselenides(disulfides)

Article abstract of DOI:10.1039/c3ra23361h

An efficient synthesis of 2-selenyl(sulfenyl)benzofurans has been accomplished through a copper(i)-catalyzed tandem reaction of 2-(gem-dibromovinyl)phenols with diorganyl diselenides and disulfides in the presence of CuI/Mg/t-BuOLi in DMSO. Using this protocol, a variety of 2-selenyl(sulfenyl)benzofuran derivatives were obtained in good yields.

Full text of DOI:10.1039/c3ra23361h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Synthesis of 2-selenyl(sulfenyl)benzofurans via Cu-
catalyzed tandem reactions of 2-(gem-
dibromovinyl)phenols with diorganyl
diselenides(disulfides)3
Cite this: RSC Advances, 2013, 3,
4723
Jie Liu,ab Wei Chena and Lei Wang*ac
Received 17th December 2012,
Accepted 21st January 2013
An efficient synthesis of 2-selenyl(sulfenyl)benzofurans has been accomplished through a copper(I)-
catalyzed tandem reaction of 2-(gem-dibromovinyl)phenols with diorganyl diselenides and disulfides in
the presence of CuI/Mg/t-BuOLi in DMSO. Using this protocol, a variety of 2-selenyl(sulfenyl)benzofuran
derivatives were obtained in good yields.
DOI: 10.1039/c3ra23361h
www.rsc.org/advances
via the transition-metal-catalyzed cross-coupling tandem reac-
tions, such as C–O/C–C,10 C–O/C–H,11 and C–O/C–P,12 have
Introduction
The benzofuran nucleus is abundant in natural products and
artificial compounds possessing potent biological activities,1
including a wide variety of therapeutic applications such as
antiviral, anticancer, insecticidal, immunosuppressive and so
on.2 For example, SKF-64346, affording a new class of potential
multifunctional drugs for Alzheimer’s disease, has been
identified as efficient inhibitors of b-amyloid aggregation.3
And Eupomatenoid 6 has shown antifungal, insecticidal, and
antioxidant activities.4 For these reasons, great efforts have
been directed for the development of practical synthetic
strategies for the assembly of the privileged substituted
benzofurans.5 One of the reliable approach for the synthesis
of benzofurans was based on the electrophilic cyclization of
the corresponding 2-(1-alkynyl)phenols, which were generated
from o-halophenols with alkynes via palladium-catalyzed
Sonogashira reactions.6 Most recently, Li7 and our group8
have developed the concise methods using simple phenols
without halogen substituent as starting materials with
b-ketoesters and propiolates to construct them directly.
been reported. During the investigation of the Pd- and Cu-
catalyzed tandem reactions, Lautens suggested that the
reactions were through 2-bromobenzofurans intermediates.
And importantly, 2-bromobenzofurans from Cu-catalyzed
intramolecular reactions of 2-(gem-dibromovinyl)phenols were
isolated by Lautens.13 Following that, we reported a TBAF-
promoted the reaction of gem-dibromoolefins for the synthesis
of 2-bromobenzofurans(thiophenes).14
Organic chalcogenide compounds have attracted consider-
able interest in organic synthesis,15 and the pharmaceutical
industry from the view of their potential biological activities,
such as antitumor, antiviral, antioxidant, anticancer and
antimicrobial properties.16 And they also can be used as
catalysts.17 The organoselenium compounds can be prepared
via nucleophile, electrophile reagents and via radical reac-
tions.18 It is important to note that a magnesium-induced Cu-
catalyzed synthesis of unsymmetrical diaryl chalcogenide
compounds from aryl iodide via cleavage of the Se–Se or S–S
bond was developed by Taniguchi et al.19 However, to the best
of our knowledge, introduction of the selenium and sulfur
moieties into 2-position of benzofurans was less investiga-
ted.5b,20
The gem-dihaloolefins, as one of the important building
blocks for the synthesis of various heterocycles, especially for
benzofuran derivatives, have attracted much attention owing
to their ready availability and higher reactivity.9 The formation
of benzofuran derivatives from 2-(gem-dibromovinyl)phenols
aDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P R
China. E-mail: leiwang@chnu.edu.cn; Fax: +86-561-309-0518;
Tel: +86-561-380-2069
bCollege of Chemistry, Chemical Engineering and Materials Science, Soochow
University, Suzhou, Jiangsu 215123, P. R. China
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai, 20032, P. R. China
Following our research on the synthesis of benzofurans
from gem-dihaloolefins,14,21 herein we wish to report an
Electronic supplementary information (ESI) available. See DOI: 10.1039/
3
c3ra23361h
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 4723–4730 | 4723

View Article Online
Paper
RSC Advances
PPh3 were examined, however, the reactions offered the
desired product 3a in lower yield (Table 1, entries 2–4). To
our delight, the yield of 3a was increased to 80% after the
addition of metallic Mg to the reaction mixture, indicating that
it plays an important role as a reducing agent to break Se–Se
bond in substrate 2a (Table 1, entry 5). The inferior yield of 3a
was obtained when Zn metal was used instead of Mg(0) in the
model reaction (Table 1, entry 6). The effect of the base on the
reaction was also investigated and t-BuOLi proved to be the
best of choice. Other bases, KOH, K3PO4, t-BuOK, Na2CO3,
Cs2CO3, NaOAc were subsequently inferior and generated 3a in
16–68 yields (Table 1, entries 7–12). On the other hand, a series
of other copper catalysts, including CuBr, CuCl, Cu2O, CuO
and CuBr2 were tested and they displayed less reactivity to CuI
in the model reaction (Table 1, entries 13–17). The solvent also
plays an important role in the model reaction. Among the
examined solvents, DMSO was found to be the most suitable
one for the reaction. When the reaction was carried out in
NMP, DMF and toluene, only 25–46% yields of 3a were
obtained (Table 1, entries 18–20). However, the reaction did
not occur when EtOH and DCE were used as reaction media
(Table 1, entries 21 and 22). The excess of Mg used in the
reaction can overcome the oxidation problems of Cu(I) being
partially oxidized into Cu(II) and thiols being partially oxidized
into disulfides under air.
Scheme 1 The tandem reaction of 2-(gem-dibromovinyl)phenols with diorganyl
diselenides(disulfides).
efficient tandem reaction of 2-(gem-dibromovinyl)phenols with
diorganyl diselenides and disulfides in the presence of CuI/
Mg/t-BuOLi. The one-pot reactions generated the correspond-
ing 2-selenylbenzofurans and 2-sulfenylbenzofurans in good
yields (Scheme 1).
Results and discussion
As indicated in Table 1, our preliminary exploration gave 41%
yield of 2-(phenylselanyl)benzofuran (3a) when 2-(gem-dibro-
movinyl)phenol (1a) reacted with diphenyldiselenide (2a) in
2 : 1 molar ratio using CuI (10 mol%) and t-BuOLi (4.0 equiv)
in DMSO (Table 1, entry 1). To enhance the efficiency of the C–
Se bond formation, several ligands, such as Phen, Bipy and
With the optimal reaction conditions in hand, the scope
and generality of this tandem reaction were examined, the
results are listed in Scheme 2. Substrates 1 bearing electron-
donating groups on the aromatic rings reacted with 2a
smoothly to generate the corresponding products in good
yields (Scheme 2, 3b–h). Halogen substitution on the benzene
ring of 1i was also tolerated. It is noteworthy that sterically
demanding ortho- and meta-substituents on substrates 1 did
not hamper the C–Se bond formation, providing the desired
products in 63–78% yields (Scheme 2, 3c–f).
On the other hand, the tandem reaction of 2-(gem-
dibromovinyl)phenols (1) with diphenyldisulfide (2b) was also
examined. The results indicated that 1 with electron-neutral,
electron-donating and electron-withdrawing substituents on
the phenols coupled with 2b very efficiently and afforded the
corresponding products in 70–81% yields under the present
reaction conditions (Scheme 2, 3j–r). It is obvious that the
reactions are not sensitive to their electronic characters and
locations of the substituted groups on the benzene rings.
However, all attempts to the coupling of 2-(gem-dibromovi-
nyl)phenol with diphenylditelluride were not successful, the
reaction only stays in the stage of 2-bromobenzofuran
formation.
Table 1 Optimization of the reaction conditions for the model reactiona
Entry
Cu catalyst
Base
Additive
Solvent
Yield (%)b
1
2
3
4
5
CuI
CuI
CuI
CuI
CuI
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
—
DMSO
DMSO
DMSO
DMSO
DMSO
41
32c
23d
18e
80
80f
71
68
57
52
34
31
16
61
52
44
49
21
46
33
25
0
Phen
Bipy
PPh3
Mg
6
7
8
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuBr
CuCl
Cu2O
CuO
CuBr2
CuI
CuI
CuI
CuI
CuI
t-BuOLi
KOH
K3PO4
Zn
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
NMP
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
9
t-BuOK
Na2CO3
Cs2CO3
NaOAc
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
10
11
12
13
14
15
16
17
18
19
20
21
22
To further extend the scope of our coupling protocol, we
turned to explore the generality of various dichalcogenides, the
results are presented in Scheme 3. It was gratifying to find that
diorganyl diselenides, including di(p-methyl)phenyldiselenide
and di(p-methoxy)phenyldiselenide, and diorganyl disulfides
with different functional groups, such as methyl and chloro
groups on the para-positions of benzene rings, were success-
fully reacted with 1a to give the corresponding products in
DMF
Toluene
EtOH
DCE
0
a
Reaction conditions: 1a (0.50 mmol), 2a (0.25 mmol), Cu catalyst
(10 mol%), base (2.0 mmol), metal additive (1.00 mmol), solvent (2.0
b
c
mL), sealed tube, 110 uC, air, 12 h. Isolated yields. Phen = 1,10-
d
e
phenanthroline (10 mol%). Bipy = bipyridine (10 mol%). PPh3 (10
mol%). Under nitrogen atmosphere.
f
4724 | RSC Adv., 2013, 3, 4723–4730
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
Scheme 3 The scope of diorganyl dichalcogenides in the tandem reaction.a
reaction of deuterium-labeled 2-(gem-dibromovinyl)phenol (1a-
D) was carried out in the presence of CuI/Mg/t-BuOLi/DMSO,
2-bromo-3-D-benzofuran and 2-bromobenzofuran were iso-
lated in 94% total yields with a ratio of 90 : 10 (Scheme 4, eq.
1), which showed the fact that 2-bromobenzofuran was formed
via an intramolecular Ullmann reaction process in major, and
via an intermediate (2-hydroxyphenyl)ethynyl bromide in
minor.21a,22 On the other hand, prepared 2-bromobenzofuran
reacted with 2a under the optimal reaction conditions,
providing 3a in 86% yield (Scheme 4, eq. 2). According to
Scheme 2 The scope of 2-(gem-dibromovinyl)phenols in the tandem reaction.a
good yields (Scheme 3, 3s–v). Under the present reaction
conditions, di(naphthalen-2-yl)disulfide underwent the reac-
tion with 1a smoothly to generate 3w in 72% yield. We tried a
reaction of di(p-nitro)phenyldisulfide bearing an electron-
withdrawing substituent on the benzene ring with 1a, but no
desired product was detected. It is important to note that
di(aliphatic)disulfide, such as di(n-propyl)disulfide can react
with 1a to afford the product 3x in 53% yield.
When 1a was subjected to the present reaction conditions
in the absence of diselenide(disulfide), 2-bromobenzofuran
was isolated in 95% yield. To further investigate the reaction
mechanism, an isotope experiment was conducted. While the
Scheme 4 Related experiments and proposed reaction mechanism.
RSC Adv., 2013, 3, 4723–4730 | 4725
This journal is ß The Royal Society of Chemistry 2013

View Article Online
Paper
RSC Advances
mmol), CuI (0.050 mmol), and DMSO (2.0 mL). The rubber
septum was then replaced by a Teflon-coated screw cap and
the reaction vessel was placed in an oil bath at 110 uC. After
stirring the mixture at this temperature for 12 h, it was cooled
to room temperature and diluted with ethyl acetate, washed
with water and brine and the organic phase was dried over
MgSO4. After the solvent was removed under reduced pressure,
the residue was purified by column chromatography on silica
gel (eluant : petroleum ether) to afford the corresponding
product.
our results and the related literatures, a plausible mechanism,
which accounts for the formation of the 2-selenyl(sulfenyl)-
benzofuran from 2-(gem-dibromovinyl)phenol and diaryldise-
lenide(disulfide) precursors, is shown in Scheme 4. On the
basis of these evidences, we believe that the formation of
2-bromobenzofuran (A) is via a Cu-catalyzed intramolecular
Ullmann reaction process (Path a).10 Meanwhile, ArYYAr
reacted with Cu(0) which was rated in situ from the reduction
of Cu(I) with Mg(0), to afford ArYCu(II)YAr (B) by an oxidative
addition, and followed by a reduction with Mg metal to
produce ArYCu(I) species (Path b).19 The obtained ArYCu(I)
then reacted with A via its insertion into the C–Br bond of A, to
obtain intermediate C. Finally, a reductive elimination of C
generated the desired product, along with releasing CuI for the
next run.
Characterization data for all products
3a: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.61–7.59 (m, 1H),
7.54–7.51 (m, 3H), 7.35–7.25 (m, 5H), 7.09 (s, 1H); 13C NMR
(100 MHz, CDCl3): d 157.46, 143.57, 131.56, 129.81, 129.40,
128.50, 127.49, 124.80, 122.94, 120.65, 115.84, 111.25. HRMS
(EI) ([M]+) Calcd. for C14H10O80Se: 273.9897, Found: 273.9900.
Conclusion
In summary, we have established an efficient and practical
strategy for the synthesis of 2-selenylbenzofurans and 2-sulfe-
nylbenzofurans through a tandem reaction of 2-(gem-dibro-
movinyl)phenols with diorganyl diselenides and disulfides as
staring materials. The reactions underwent smoothly in the
presence of CuI/Mg/t-BuOLi and generated the desired
products in good yields. Moreover, the methodology has the
advantage of being an economical and simple procedure. The
further application of this type of reaction and detailed
mechanistic study are currently underway.
3b: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.61 (s, 1H), 7.53–
7.50 (m, 2H), 7.47–7.40 (m, 2H), 7.29–7.28 (m, 3H), 7.08 (s, 1H),
1.43 (s, 9H); 13C NMR (100 MHz, CDCl3): d 155.77, 146.03,
143.30, 131.33, 130.15, 129.36, 128.20, 127.35, 122.87, 116.80,
116.37, 110.58, 34.69, 31.78. HRMS (EI) ([M]+) Calcd. for
Experimental section
C
18H18O74Se: 324.0582, Found: 324.0579.
General remarks
All the tandem reactions of gem-dibromoolefins with diorganyl
diselenides or disulfides were carried out under an air
1
atmosphere. H NMR, 13C NMR spectra were measured on a
Bruker Avance NMR spectrometer (400 MHz or 100 MHz,
respectively) with CDCl3 as solvent and recorded in ppm
relative to internal tetramethylsilane standard. The peak
patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; m, multiplet; q, quartet. The coupling constants, J, are
reported in Hertz (Hz). High resolution mass spectroscopy
data of the product were collected on a Waters Micromass GCT
instrument.
Solvents, and general chemicals were purchased from
commercial suppliers and used without further purification.
All the gem-dibromovinyl substrates were synthesized accord-
ing to the reported procedures in the literature.13,23 The 2a, 2b,
2x were purchased from commercial suppliers, 2s and 2t were
synthesized according to the reported procedure in the
literature.24 2u–w were synthesized according to the reported
procedure in the literature.25
3c: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.50–7.48 (m, 2H),
7.33–7.27 (m, 4H), 7.10–7.08 (m, 1H), 7.04 (s, 1H), 2.46 (s, 3H),
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): d 157.25, 142.14,
133.43, 131.08, 130.63, 129.37, 127.24, 125.92, 125.11, 119.91,
117.25, 116.80, 19.26, 11.81. HRMS (EI) ([M]+) Calcd. for
C
16H14O74Se: 296.0269, Found: 296.0271.
3d: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.87–7.85 (m, 2H),
7.58–7.48 (m, 6H), 7.43–7.40 (m, 1H), 7.36–7.30 (m, 4H), 7.08
(s, 1H); 13C NMR (100 MHz, CDCl3): d 154.74, 144.16, 136.15,
132.16, 129.69, 129.48, 129.45, 128.63, 128.61, 127.73, 127.71,
Typical procedure for the tandem reaction. A sealable
reaction tube equipped with a magnetic stirrer bar was
charged with 2-(gem-dibromovinyl)phenol (0.50 mmol), dis-
elenide or disulfide (0.25 mmol), Mg (1.0 mmol), t-BuOLi (2.0
4726 | RSC Adv., 2013, 3, 4723–4730
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
125.29, 124.22, 123.55, 119.76, 115.28. HRMS (EI) ([M]+) Calcd.
for C20H14O74Se: 344.0269, Found: 344.0264.
3i: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.53–7.51 (m, 3H),
7.40–7.38 (m, 1H), 7.32–7.28 (m, 3H), 7.26–7.23 (m, 1H), 6.95
(s, 1H); 13C NMR (100 MHz, CDCl3): d 155.75, 145.81, 132.11,
129.79, 129.52, 129.08, 128.59, 127.87, 124.88, 120.09, 114.65,
112.15. HRMS (EI) ([M]+) Calcd. for C14H9OCl74Se: 301.9567,
Found: 301.9570.
3e: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.48–7.46 (m, 2H),
7.29–7.26 (m, 3H), 7.19 (s, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 2.49
(s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): d 155.17,
142.83, 132.45, 131.06, 130.45, 129.34, 128.09, 127.22, 127.19,
120.98, 117.80, 116.35, 21.21, 15.06. HRMS (EI) ([M]+) Calcd.
for C16H14O74Se: 296.0269, Found: 296.0267.
3j: White solid,26 m.p. 50.4–51.5 uC. 1H NMR (400 MHz,
CDCl3): d 7.62–7.60 (m, 1H), 7.52–7.50 (m, 1H), 7.40–7.25 (m,
7H), 7.09 (s, 1H); 13C NMR (100 MHz, CDCl3): d 156.72, 147.83,
134.19, 129.20, 129.00, 128.29, 127.05, 125.15, 123.02, 120.89,
114.34, 111.34. HRMS (EI) ([M]+) Calcd. for C14H10OS:
226.0452, Found: 226.0454.
3f: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.52–7.50 (m, 2H),
7.43–7.41 (m, 1H), 7.32–7.26 (m, 3H), 7.19–7.16 (m, 1H), 7.14–
7.12 (m, 1H), 7.07 (s, 1H), 2.55 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 156.65, 143.02, 131.28, 130.17, 129.36, 127.98,
127.34, 125.71, 122.97, 121.54, 118.09, 116.38, 15.12. HRMS
(EI) ([M]+) Calcd. for C15H12O74Se: 282.0113, Found: 282.0118.
3k: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.46 (d, J = 7.3
Hz, 1H), 7.41–7.39 (m, 2H), 7.36–7.32 (m, 2H), 7.29–7.17 (m,
3H), 7.10 (s, 1H), 2.57(s, 3H); 13C NMR (100 MHz, CDCl3): d
155.91, 147.23, 134.62, 129.12, 128.65, 127.79, 126.83, 126.05,
123.04, 121.62, 118.32, 114.96, 15.05. HRMS (EI) ([M]+) Calcd.
for C15H12OS: 240.0609, Found: 240.0610.
3g: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.51–7.49 (m, 2H),
7.40–7.37 (m, 2H), 7.30–7.27 (m, 3H), 7.14–7.13 (m, 1H), 7.02
(s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3): d 155.96,
143.35, 132.42, 131.33, 130.07, 129.37, 128.58, 127.37, 126.13,
120.41, 115.83, 110.76, 21.26. HRMS (EI) ([M]+) Calcd. for
C15H12O74Se: 282.0113, Found: 282.0109.
1
3l: Colourless oil. H NMR (400 MHz, CDCl3): d 7.47–7.44 (m,
1H), 7.39–7.36 (m, 2H), 7.33–7.29 (m, 2H), 7.27–7.20 (m, 3H),
7.04 (s, 1H), 1.50 (s, 9H); 13C NMR (100 MHz, CDCl3): d 155.06,
146.66, 134.90, 134.70, 129.10, 128.89, 128.84, 126.88, 122.97,
121.68, 118.83, 113.89, 34.30, 29.72. HRMS (EI) ([M]+) Calcd.
for C18H18OS: 282.1078, Found: 282.1079.
3h: Yellow oil. 1H NMR (400MHz, CDCl3): d 7.50–7.48 (m, 2H),
7.38 (d, J = 9.0 Hz, 1H), 7.30–7.26 (m, 3H), 7.02 (d, J = 2.4 Hz,
1H), 7.00 (d, J = 0.8 Hz, 1H), 6.93–6.90 (m, 1H), 3.85 (s, 3H); 13
C
NMR (100 MHz, CDCl3): d 155.98, 152.58, 144.05, 131.47,
129.94, 129.41, 128.98, 127.46, 115.98, 113.77, 111.73, 102.77,
55.85. HRMS (EI) ([M]+) Calcd. for C15H12O274Se: 298.0062,
Found: 298.0061.
3m: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.35–7.32 (m,
2H), 7.30–7.26 (m, 2H), 7.24–7.20 (m, 1H), 7.19–7.16 (m, 2H),
7.05 (s, 1H), 6.86–6.81 (m, 1H), 3.99 (s, 3H); 13C NMR (100
MHz, CDCl3): d 148.09, 146.20, 145.13, 134.44, 129.91, 129.14,
128.87, 126.92, 123.68, 115.00, 113.12, 107.19, 56.00. HRMS
(EI) ([M]+) Calcd. for C15H12O2S: 256.0558, Found: 256.0560.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 4723–4730 | 4727

View Article Online
Paper
RSC Advances
131.91, 130.75, 129.52, 128.72, 128.21, 120.57, 117.08, 112.64,
111.55. HRMS (EI) ([M]+) Calcd. for C14H9O3NS: 271.0303,
Found: 271.0304.
3n: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.40–7.35 (m,
3H), 7.34–7.30 (m, 2H), 7.28–7.24 (m, 1H), 7.04 (d, J = 2.6 Hz,
1H), 7.02 (s, 1H), 6.98–6.95 (m, 1H), 3.87 (s, 3H); 13C NMR (100
MHz, CDCl3): d 156.00, 151.75, 148.27, 134.30, 129.16, 128.87,
128.75, 126.97, 114.44, 114.14, 111.82, 102.92, 55.77. HRMS
(EI) ([M]+) Calcd. for C15H12O2S: 256.0558, Found: 256.0554.
3s: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.56–7.54 (m, 1H),
7.48–7.43 (m, 3H), 7.30–7.26 (m, 1H), 7.24–7.21 (m, 1H), 7.11–
7.09 (m, 2H), 6.99 (s, 1H), 2.33 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 157.44, 137.82, 133.01, 132.34, 130.23, 128.64,
125.74, 124.61, 122.89, 120.53, 114.96, 111.22, 21.07. HRMS
(EI) ([M]+) Calcd. for C15H12O74Se: 282.0113, Found: 282.0112.
3o: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.36–7.34 (m,
2H), 7.31–7.22 (m, 4H), 6.92–6.91 (m, 2H), 3.96 (s, 3H); 13C
NMR (100 MHz, CDCl3): d 149.97, 145.42, 145.04, 133.67,
131.07, 129.51, 129.30, 127.37, 116.21, 115.70, 113.55, 110.80,
56.32. HRMS (EI) ([M]+) Calcd. for C15H11O2SBr: 333.9663,
Found: 333.9666.
3t: Yellow oil. 1H NMR (400 MHz, CDCl3): d 7.56–7.51 (m, 3H),
7.47–7.45 (m, 1H), 7.28–7.19 (m, 2H), 6.91 (s, 1H), 6.86–6.84
(m, 2H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3): d 159.84,
157.33, 145.26, 134.89, 128.67, 124.43, 122.86, 120.43, 119.06,
115.16, 113.89, 111.14, 55.31. HRMS (EI) ([M]+) Calcd. for
C15H12O274Se: 298.0062, Found: 298.0059.
3p: White solid, m.p. 59.9–60.4 uC. 1H NMR (400 MHz, CDCl3):
d 7.53 (d, J = 2.0 Hz, 1H), 7.41–7.32 (m, 5H), 7.30–7.26 (m, 2H),
6.95 (s, 1H); 13C NMR (100 MHz, CDCl3): d 154.89, 150.14,
133.29, 129.61, 129.54, 129.28, 128.62, 127.45, 125.17, 120.28,
112.93, 112.21. HRMS (EI) ([M]+) Calcd. for C14H9ClOS:
260.0063, Found: 260.0066.
3u: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.55 (d, J = 7.6
Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.32–7.22 (m, 4H), 7.14–7.12
(m, 2H), 6.98 (s, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 156.67, 148.97, 137.49, 130.20, 130.02, 130.00, 128.45, 124.92,
122.97, 120.75, 113.21, 111.30, 21.03. HRMS (EI) ([M]+) Calcd.
for C15H12OS: 240.0609, Found: 240.0610.
3q: White solid, m.p. 50.5–51.4 uC. 1H NMR (400 MHz, CDCl3):
d 7.69 (d, J = 2.0 Hz, 1H), 7.42–7.36 (m, 3H), 7.35–7.31 (m, 3H),
7.30–7.26 (m, 1H), 6.94 (s, 1H); 13C NMR (100 MHz, CDCl3): d
155.29, 150.04, 133.28, 130.20, 129.66, 129.32, 127.89, 127.49,
123.37, 116.13, 112.78, 112.71. HRMS (EI) ([M]+) Calcd. for
C14H9BrOS: 303.9557, Found: 303.9554.
3v: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.58 (d, J = 7.6
Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.36–7.32 (m, 1H), 7.30–7.25
(m, 5H), 7.06 (s, 1H); 13C NMR (100 MHz, CDCl3): d 156.83,
147.27, 133.29, 132.76, 130.42, 129.37, 128.23, 125.39, 123.17,
121.00, 114.58, 111.40. HRMS (EI) ([M]+) Calcd. for C14H9OSCl:
260.0063, Found: 260.0067.
3r: Yellow solid, m.p. 82.7–83.4 uC. 1H NMR (400 MHz, CDCl3):
d 8.46 (d, J = 2.4 Hz, 1H), 8.22 (dd, J = 9.0, 2.3 Hz, 1H), 7.52 (d, J
= 9.0 Hz, 1H), 7.46–7.43 (m, 2H), 7.39–7.33 (m, 3H), 7.04 (s,
1H); 13C NMR (100 MHz, CDCl3): d 159.09, 153.48, 144.22,
3w: Colourless oil. 1H NMR (400 MHz, CDCl3): d 8.33–8.31 (m,
1H), 7.80–7.77 (m, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.56–7.53 (m,
2H), 7.47 (d, J = 7.6 Hz, 1H), 7.41–7.38 (m, 2H), 7.27–7.23 (m,
4728 | RSC Adv., 2013, 3, 4723–4730
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
2H), 7.21–7.17 (m, 1H), 6.82 (s, 1H); 13C NMR (100 MHz,
CDCl3): d 156.35, 153.96, 148.65, 135.56, 131.07, 128.25,
127.81, 127.54, 125.87, 124.81, 124.03, 123.10, 123.09, 120.74,
120.60, 111.17, 110.67, 108.59. HRMS (EI) ([M]+) Calcd. for
C18H12OS: 276.0609, Found: 276.0614.
8 (a) S. Wang, P. Li, L. Yu and L. Wang, Org. Lett., 2011, 13,
5968; (b) C. Li, Y. Zhang, P. Li and L. Wang, J. Org. Chem.,
2011, 76, 4692.
9 (a) For a selected review, see: G. Chelucci, Chem. Rev., 2012,
112, 1344; (b) For selected examples, see: K. Jouvin,
A. Bayle, F. Legrand and G. Evano, Org. Lett., 2012, 14,
1652; (c) Z.-J. Wang, F. Yang, X. Lv and W. Bao, J. Org.
Chem., 2011, 76, 967; (d) M. L. N. Rao, D. N. Jadhav and
P. Dasgupta, Org. Lett., 2010, 12, 2048; (e) S. G. Newman
and M. Lautens, J. Am. Chem. Soc., 2010, 132, 11416; (f) C.
S. Bryan, J. A. Braunger and M. Lautens, Angew. Chem., Int.
Ed., 2009, 48, 7064; (g) A. Coste, G. Karthikeyan, F. Couty
and G. Evano, Angew. Chem., Int. Ed., 2009, 48, 4381; (h)
M. Arthuis, R. Pontikis and J.-C. Florent, Org. Lett., 2009,
11, 4608; (i) C. S. Bryan and M. Lautens, Org. Lett., 2008, 10,
4633; (j) T. O. Vieira, L. A. Meaney, Y.-L. Shi and H. Alper,
Org. Lett., 2008, 10, 4899; (k) A. Fayol, Y.-Q. Fang and
M. Lautens, Org. Lett., 2006, 8, 4203.
3x: Colourless oil. 1H NMR (400 MHz, CDCl3): d 7.50 (d, J = 7.4
Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.29–7.14 (m, 2H), 6.78 (s, 1H),
2.94 (t, J = 7.2 Hz, 2H), 1.76–1.67 (m, 2H), 1.04 (t, J = 7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 156.28, 150.87, 128.69,
124.19, 122.81, 120.26, 110.87, 110.62, 36.64, 23.13, 13.06.
HRMS (EI) ([M]+) Calcd. for C11H12OS: 192.0609, Found:
192.0611.
10 M. Nagamochi, Y.-Q. Fang and M. Lautens, Org. Lett., 2007,
9, 2955.
11 (a) S. Ye, G. Liu, S. Pu and J. Wu, Org. Lett., 2012, 14, 70; (b)
X. Qin, X. Cong, D. Zhao, J. You and J. Lan, Chem.
Commun., 2011, 47, 5611.
12 S. Thielges, E. Meddah, P. Bisseret and J. Eustache,
Tetrahedron Lett., 2004, 45, 907.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Nos. 21172092, 20972057).
13 S. G. Newman, V. Aureggi, C. S. Bryan and M. Lautens,
Chem. Commun., 2009, 5236.
14 W. Chen, Y. Zhang, L. Zhang, M. Wang and L. Wang, Chem.
Commun., 2011, 47, 10476.
References
1 (a) C. Kirilmis, M. Ahmedzade, S. Servi, M. Koca, A. Kizirgil
and C. Kazaz, Eur. J. Med. Chem., 2008, 43, 300; (b)
W. Kurosawa, T. Kan and T. Fukuyama, J. Am. Chem. Soc.,
2003, 125, 8112; (c) B. M. Trost and W. Tang, Angew. Chem.,
Int. Ed., 2002, 41, 2795.
˜
15 (a) G. Perin, E. J. Lenardao, R. G. Jacob and R. B. Panatieri,
Chem. Rev., 2009, 109, 1277; (b) D. Singh, E. E. Alberto, O.
E. D. Rodrigues and A. L. Braga, Green Chem., 2009, 11,
1521; (c) V. P. Reddy, A. V. Kumar, K. Swapna and K. R. Rao,
Org. Lett., 2009, 11, 951; (d) M. Wang, K. Ren and L. Wang,
Adv. Synth. Catal., 2009, 351, 1586; (e) X. Zhao, Z. Yu,
S. Yan, S. Wu, R. Liu, W. He and L. Wang, J. Org. Chem.,
2005, 70, 7338; (f) K. Ajiki, M. Hirano and K. Tanaka, Org.
Lett., 2005, 7, 4193; (g) T. Nishino, M. Okada, T. Kuroki,
T. Watanabe, Y. Nishiyama and N. Sonoda, J. Org. Chem.,
2002, 67, 8696; (h) Y. Nishiyama, K. Tokunaga and
N. Sonoda, Org. Lett., 1999, 1, 1725.
2 (a) H.-A. Du, X.-G. Zhang, R.-Y. Tang and J.-H. Li, J. Org.
Chem., 2009, 74, 7844; (b) M. Carril, R. SanMartin, I. Tellitu
´
and E. Domınguez, Org. Lett., 2006, 8, 1467; (c) J. A. Findlay,
S. Buthelezi, G. Li, M. Seveck and J. D. Miller, J. Nat. Prod.,
1997, 60, 1214; (d) M. Nakamura, L. Ilies, S. Otsubo and
E. Nakamura, Org. Lett., 2006, 8, 2803.
`
3 S. Rizzo, C. Riviere, L. Piazzi, A. Bisi, S. Gobbi, M. Bartolini,
V. Andrisano, F. Morroni, A. Tarozzi, J.-P. Monti and
A. Rampa, J. Med. Chem., 2008, 51, 2883.
4 (a) M. Carini, G. Aldini, M. Orioli and R. M. Facino, Planta
Med., 2002, 68, 193; (b) B. Freixa, R. Vila, E. A. Ferro,
16 (a) For a selected review, see: C. W. Nogueira, G. Zeni and J.
B. T. Rocha, Chem. Rev., 2004, 104, 6255; (b) G. Mugesh, W.
W. Du Mont and H. Sies, Chem. Rev., 2001, 101, 2125; (c)
For a selected example, see: T. G. Back and Z. Moussa, J.
Am. Chem. Soc., 2003, 125, 13455.
˜
T. Adzet and S. Canigueral, Planta Med., 2001, 67, 873.
5 (a) For a selected review, see: D. A. Horton, G. T. Bourne
and M. L. Smythe, Chem. Rev., 2003, 103, 893; (b) For
selected examples, see: F. Manarin, J. A. Roehrs, R. M. Gay,
17 A. L. Braga, F. Vargas, J. A. Sehnem and R. C. Braga, J. Org.
Chem., 2005, 70, 9021.
18 (a) S. Fukuzawa, D. Tanihara and S. Kikuchi, Synlett, 2006,
2145; (b) L. Wang and Y. Zhang, Heteroat. Chem., 1999, 10,
203; (c) W. Bao, Y. Zheng, Y. Zhang and J. Zhou,
Tetrahedron Lett., 1996, 37, 9333; (d) M. Sakakibara,
K. Katsumata, Y. Watanabe, T. Toru and Y. Ueno,
Synthesis, 1992, 377; (e) S. Fukuzawa, Y. Niimoto,
T. Fujinami and S. Sakai, Heteroat. Chem., 1990, 1, 491;
(f) M. R. Detty, J. Org. Chem., 1980, 45, 274.
19 (a) N. Taniguchi and T. Onami, J. Org. Chem., 2004, 69, 915;
(b) N. Taniguchi and T. Onami, Synlett, 2003, 829.
20 (a) M. A. Abramov, W. Dehaen, B. D’hooge, M. L. Petrov,
S. Smeets, S. Toppet and M. Voets, Tetrahedron, 2000, 56,
3933; (b) M. L. Petrov, D. A. Androsov, M. A. Abramov, I.
˜
R. Brandao, P. H. Menezes, C. W. Nogueira and G. Zeni, J.
Org. Chem., 2009, 74, 2153; (c) B. Zhao and X. Lu, Org. Lett.,
2006, 8, 5987.
6 (a) T. Okitsu, D. Nakazawa, R. Taniguchi and A. Wada, Org.
Lett., 2008, 10, 4967; (b) A. Fu¨rstner, E. K. Heilmann and P.
W. Davies, Angew. Chem., Int. Ed., 2007, 46, 4760; (c)
I. Nakamura, Y. Mizushima and Y. Yamamoto, J. Am. Chem.
Soc., 2005, 127, 15022; (d) D. Yue, T. Yao and R. C. Larock, J.
Org. Chem., 2005, 70, 10292; (e) Y. Liao, J. Smith, R. Fathi
and Z. Yang, Org. Lett., 2005, 7, 2707.
7 X. Guo, R. Yu, H. Li and Z. Li, J. Am. Chem. Soc., 2009, 131,
17387.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 4723–4730 | 4729

View Article Online
Paper
P. Abramova, W. Dehaen and Y. I. Lyakhovetskii, Russ. J.
RSC Advances
23 S. Bhatt and S. K. Nayak, Tetrahedron Lett., 2009, 50, 5823.
24 D. Singh, A. M. Deobald, L. R. S. Camargo, G. Tabarelli, O.
E. D. Rodrigues and A. L. Braga, Org. Lett., 2010, 12, 3288.
25 G. W. Kabalka, M. S. Reddy and M.-L. Yao, Tetrahedron
Lett., 2009, 50, 7340.
Org. Chem., 2006, 42, 1521.
21 (a) J. Liu, W. Chen, Y. Ji and L. Wang, Adv. Synth. Catal.,
2012, 354, 1585; (b) W. Zhou, W. Chen and L. Wang, Org.
Biomol. Chem., 2012, 10, 4172.
22 (a) H. Xu, S. Gu, W. Chen, D. Li and J. Dou, J. Org. Chem.,
2011, 76, 2448; (b) M. Okutani and Y. Mori, J. Org. Chem.,
2009, 74, 442.
26 H.-J. Xu, Y.-Q. Zhao, T. Feng and Y.-S. Feng, J. Org. Chem.,
2012, 77, 2878.
4730 | RSC Adv., 2013, 3, 4723–4730
This journal is ß The Royal Society of Chemistry 2013