Copper/silver-mediated cascade reactions for the construction of 2-sulfonylbenzo[b]furans from trans-2-hydroxycinnamic acids and sodium sulfinates

Article abstract of DOI:10.1021/jo4024478

Efficient construction of 2-sulfonylbenzo[b]furans is achieved from readily available trans-2-hydroxycinnamic acids and sodium sulfinates mediated by the CuCl2.2H2O/AgTFA system under mild conditions. This unprecedented synthetic protocol provides expedient access to a series of products in one step via a protodecarboxylation/C-S bond formation/C-O bond formation cascade.

Full text of DOI:10.1021/jo4024478

Article
pubs.acs.org/joc
Copper/Silver-Mediated Cascade Reactions for the Construction of
2‑Sulfonylbenzo[b]furans from trans-2-Hydroxycinnamic Acids and
Sodium Sulfinates
Hong-Shuang Li† and Gang Liu*,†,‡,§
†Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Road, Xicheng
District, Beijing 100050, P. R. China
§
‡Tsinghua-Peking Center for Life Sciences and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine,
Tsinghua University, Haidian District, Beijing 100084, P. R. China
S
* Supporting Information
ABSTRACT: Efficient construction of 2-sulfonylbenzo[b]furans is achieved from readily available trans-2-hydroxycinnamic acids
and sodium sulfinates mediated by the CuCl2·2H2O/AgTFA system under mild conditions. This unprecedented synthetic
protocol provides expedient access to a series of products in one step via a protodecarboxylation/C−S bond formation/C−O
bond formation cascade.
Scheme 1. Methods for the Synthesis of 2-
Sulfonylbenzo[b]furans
INTRODUCTION
■
Benzo[b]furan, as a ubiquitous heterocyclic structural motif,
constitutes a significant component in naturally occurring
products and in drug discovery1 and thus has attracted
considerable interest from organic chemists in pursuing
synthetic efficiency.2 Among these abundant functionalized
structures, 2-sulfonylbenzo[b]furans have versatile pharmaceut-
ical activities, such as antimalarial, MMP-13 inhibitor, aldose
reductase inhibitor, 5-HT modulator, and cognitive enhancer.3
Typical strategies for the synthesis of 2-sulfonylbenzo[b]furans
involve the following: (i) deprotonation of benzofurans using n-
BuLi followed by treatment with activated 1-sulfonylbenzo-
triazoles or arenesulfonyl fluorides (Scheme 1, route A);4,3c,d
(ii) a multistep synthesis of sulfide with subsequent oxidation
with m-CPBA (route B);3a,b and (iii) methylation after
reduction of benzofuran-2-sulfonyl chloride to sodium sulfinate
(route C).3h In view of the harsh conditions and tedious
procedures required, it is desirable to develop a more facile and
efficient approach for constructing this scaffold.
In continuation of our research on the functionalization of
benzo[b]furan,5 herein we disclose a cascade reaction involving
a protodecarboxylation, an oxidative sulfonylation, and an
intramolecular C−O cyclization to afford 2-sulfonylbenzo[b]-
furans under CuCl2·2H2O/AgTFA-mediated conditions
(Scheme 1, route D).
catalyst system.9 Other approaches, including pH-dependent,10
biocatalyzed,11 or base-catalyzed12 decarboxylations, have also
been employed. Furthermore, styrenes as the decarboxylation
products were reported to be able to react with sodium
sulfinates to furnish α,β-unsaturated sulfones (vinyl sulfones)
under various oxidative conditions, including PhI(OAc)2/KI,13
CAN/NaI,14 NaIO4/KI,15 I2/NaOAc,16 and CuI-bpy/KI in
In past decades, protodecarboxylations of carboxylic acids6
mediated by transition metals (TMs) such as silver7 or copper8
have been exquisitely investigated. Among diverse carboxylic
acids, the protodecarboxylation of cinnamic acid was
successfully exploited with the Cu2O/1,10-phenanthroline
Received: September 12, 2013
© XXXX American Chemical Society
A
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air.17 In light of the harsh reaction conditions involved in the
preparation of structure-diversified styrenes,18 it would be
advantageous to use cinnamic acids (readily prepared by
Horner−Wittig reaction19 or Knoevenagel condensation20) as
alternatives to perform oxidative sulfonylation after in situ
decarboxylation.
Recently, a number of methods have been developed for the
transformation of o-alkenyl phenols into 2-substituted benzo-
[b]furans using the VO(acac)2/TBHP/acid catalyst system,21
I2/K2CO3,22 CuBr2,23 PhI(OAc)2,24 DDQ,25 or m-CPBA/
TsOH.25a,26 Additionally, Dominguez and co-workers demon-
strated an interesting cyclization of 2-hydroxy-α-arylstyrenes to
benzofurans by employing the CuOAc/8-hydroxyquinoline/
DMA/O2 system.27 Inspired by the intramolecular oxidative
cyclization, we envisioned that the anticipated 2-sulfonylbenzo-
[b]furans could be accessible via cascade reactions28 from trans-
2-hydroxycinnamic acids and sodium sulfinates in the presence
of a decarboxylation mediator and oxidants.
subsequently carried out to examine the reaction parameters.
Among the copper salts screened (entries 2−6), CuCl2·2H2O
produced a higher yield than other copper species; an isolated
yield of 53% was obtained (entry 6). Therefore, CuCl2·2H2O
was employed as the copper source on the basis of its
cheapness and high efficiency, although Cu(OTf)2 delivered a
comparable yield (entry 4). Nevertheless, the product yield was
lowered to 41% when the reaction was performed under an
atmosphere of oxygen (entry 7). It was observed that increasing
the copper loading resulted in an enhanced yield (59% with 30
mol % CuCl2·2H2O; entry 8). Furthermore, employing 50 mol
% CuCl2·2H2O increased the yield of 3aa to 67% when the
reaction was conducted at 80 °C for 18 h (entry 9).
Moreover, the amount and choice of silver salt were pivotal.
Decreasing the amount of AgTFA to 1.2 equiv was detrimental,
providing 3aa in a very poor yield (entry 10). In contrast, 2.5
equiv of AgTFA was beneficial in promoting the reaction and
afforded a good yield (entry 15). Other silver salts such as
AgOAc and Ag2CO3 were far less effective than AgTFA (entries
11 and 12, respectively). The effect of bases on the reaction
turnover was also investigated. Although the yield was slightly
diminished when K2CO3 was used as a base (entry 14), the
reaction in the presence of a strong base such as t-BuOK
provided a yield similar to that achieved with Cs2CO3 (entry
13).
RESULTS AND DISCUSSION
■
In our initial studies, commercially available trans-2-hydrox-
ycinnamic acid (1a) and p-toluenesulfinic acid sodium salt
tetrahydrate (2a) were chosen as model substrates for
optimization of the reaction conditions, and the results are
depicted in Table 1. When 1a was treated with 2a in the
Having established the optimized conditions for the
construction of 2-sulfonylbenzo[b]furans, we next explored
the substrate scope of the reaction. As summarized in Table 2, a
variety of sodium sulfinates could be reacted with trans-2-
hydroxycinnamic acids, which were readily synthesized by the
Horner−Wittig reaction.29 Sodium sulfinates bearing electron-
donating substituents such as methyl, methoxy and tert-butyl
gave the desired products (3aa, 3ab, 3ad, and 3ae) in good
yields, with the exception of 3ac, which was obtained in low
yield because of the steric hindrance of o-methyl group. Good
compatibility with functional groups for the single-step
synthesis of 2-sulfonylbenzo[b]furans was observed, with fluoro
(3ah), chloro (3ai), bromo (3aj), and acetamido groups (3al)
all being well-tolerated. The yield with the electron-with-
drawing CF3 group fell to 44% (3ak). However, exposure of
sodium sulfinate bearing a nitro group to the reaction
conditions showed that almost no product was delivered.
Electron-neutral benzenesulfinate 2f as well as the bulkier 2-
naphthylsulfinate 2g underwent this reaction smoothly to
furnish 3af and 3ag in 60% and 52% yield, respectively. It is
noteworthy that this protocol could be extended to
methanesulfinic acid sodium salt 2m, from which a good
yield of 3am was isolated.
Meanwhile, the scope of trans-2-hydroxycinnamic acids was
also evaluated. (E)-3-(2-Hydroxynaphthalen-1-yl)acrylic acid
1b was readily transformed into the target product 3ba in 81%
yield. Various substituents such as methoxy (1c, 1d), methyl
(1e), fluoro (1g, 1h), chloro (1i), and bromo (1k) were again
found to be well-tolerated, except for the difunctional group of
1j. This suggests that introducing substituents at the position
ortho to the hydroxyl group on the substrate influences this
cascade reaction, since no product was delivered either when a
substrate with a methoxy group at the same position was used.
The 5-HT modulator 3cn3g could be produced under this
CuCl2·2H2O/AgTFA-mediated reaction, albeit in low yield.
Unfortunately, the incorporation of benzofuran on the
substrate with a free phenolic hydroxyl group failed. To our
Table 1. Optimization Studies for the Construction of 2-
Sulfonylbenzo[b]furans
a
b
Ag salt
(equiv)
yield
c
entry
Cu salt (equiv)
T (°C)/t (h)
(%)
1
2
3
4
5
6
Cu(OAc)2 (0.2)
CuSO4 (0.2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (2)
AgTFA (1.2)
AgOAc (2)
Ag2CO3 (2)
AgTFA (2)
AgTFA (2)
AgTFA (2.5)
100/12
100/12
100/12
100/12
100/12
100/12
100/12
100/12
80/18
31
6
Cu(TFA)2 (0.2)
Cu(OTf)2 (0.2)
CuCl (0.2)
46
51
34
53
41
59
67
11
9
CuCl2·2H2O (0.2)
CuCl2·2H2O (0.2)
CuCl2·2H2O (0.3)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
CuCl2·2H2O (0.5)
d
7
8
9
10
11
12
80/18
80/18
80/18
14
65
58
79
e
13
f
80/18
14
80/18
15
80/18
a
Unless otherwise noted, the reactions were carried out in air using 1a
(1 equiv), 2a (1.2 equiv), and Cs2CO3 (2 equiv) in 6 mL of DMF.
b
c
d
AgTFA = silver trifluoroacetate. Isolated yields. Under an
e
f
atmosphere of O2 (1 atm). 2 equiv of t-BuOK was used. 2 equiv
of K2CO3 was used.
presence of Cu(OAc)2 (20 mol %), AgTFA (2 equiv), and
Cs2CO3 (2 equiv) under ambient atmosphere in commercial-
grade DMF (6 mL) at 100 °C for 12 h, 2-[(4-methylphenyl)-
sulfonyl]benzofuran (3aa) was isolated in 31% yield (entry 1);
1H NMR and 13C NMR analyses of the product were in
agreement with the published data.4b Intrigued by this
unexpected cascade reaction, an array of assays was
B
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a
Table 2. Synthesis of Various 2-Sulfonylbenzo[b]furans
a
Reaction conditions: 1 (1 mmol), 2 (1.2 mmol), CuCl2·2H2O (50 mol %), AgTFA (2.5 mmol), and Cs2CO3 (2.0 mmol) in 6 mL of DMF at 80 °C
b
c
d
under air for 18 h, unless otherwise noted. 80 °C, 36 h. 90 °C, 24 h. 100 °C, 24 h.
Scheme 2. Control Experiments
delight, the monobenzyl-protected trans-2-hydroxycinnamic
acid 2f reacted readily, giving rise to 3fa in 51% yield.
isolated as a major product (eq 2). Finally, combining the silver
salt with a catalytic amount of the copper salt gave 4 in an
acceptable yield (eq 3). Obviously, the copper salt improves the
efficiency of formation of the α,β-unsaturated sulfone.
Scheme 3 exemplifies the two plausible pathways by isolating
the key intermediates. On the one hand, when 5 formed by in
situ decarboxylation of 1a based on the silver salt was reacted
with 2a with and without a catalytic amount of CuCl2·2H2O
(10 mol %) under an argon atmosphere, 4 was obtained in
To shed light on the mechanism of this cascade reaction,
control experiments were performed (Scheme 2). When 1a was
treated with 2a in the presence of 2.5 equiv of AgTFA and 2
equiv of Cs2CO3 under an argon atmosphere, 2-(2-
sulfonylvinyl)phenol 4 was produced in 28% isolated yield
along with the protodecarboxylation product 5 in 12% isolated
yield (eq 1). In addition, with 10 mol % CuCl2·2H2O, 5 was
C
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Scheme 3. Studies of Two Plausible Pathways
Scheme 4. Proposed Mechanism
isolated yields of 82% and 45%, respectively (pathway A). The
results were in accordance with those of Scheme 2. Subsequent
oxidative cyclization of 4 promoted by 50 mol % CuCl2·2H2O
in air led to the formation of 3aa in good yield. We observed
that the reaction of 5 with 2a under the standard conditions
also provided the desired product 3aa in 71% yield. However,
only a trace amount of 3aa was obtained when 1a was treated
with 2a in the presence of 50 mol % copper salt only. On the
other hand, benzofuran-2-carboxylic acid 6, formed under the
analogous oxidative conditions, was not observed to produce
the sulfone 3aa upon reaction of 2a no matter the existence of
the copper salt (pathway B). Furthermore, it should be
mentioned that metallic silver is generated in all of these
cascade reactions.
is proposed, as illustrated in Scheme 4. Initial protodecarbox-
ylation of trans-2-hydroxycinnamic acid mediated by AgI or CuII
liberates 2-vinylphenol 5, as established by Larrosa7a and
Goossen.9a Meanwhile, the sodium sulfinate is oxidized by AgI
to give sulfonyl radical B as well as metallic silver, and a second
oxidation delivers sulfonyl cation C. It has been reported that
CuII coupled with ligands can also catalyze the oxidation of
sodium sulfinate, as indcated by Taniguchi.17 Subsequent anti
addition of C to alkene 5 and elimination of H+ produces α,β-
unsaturated sulfone E. The CuII salt plays a key role in the
oxidative cyclization step. In the presence of another CuII salt,
the intermediate F undergoes C−H activation to generate the
CuIII−vinyl species G.30 Finally, reductive elimination provides
the target product H, and the CuI salt is reoxidized using air to
regenerate the CuII salt. However, C−H functionalization/C−
O cyclization cannot be ruled out in the second step.31
On the basis of the above investigations, a tentative
mechanism for the construction of 2-sulfonylbenzo[b]furans
D
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°C; 1H NMR (400 MHz, acetone-d6) δ 10.74 (br s, 1H), 9.63 (s, 1H),
7.95 (d, J = 16.4 Hz, 1H), 7.26 (m, 1H), 6.81−6.85 (m, 2H), 6.71 (m,
1H); 13C NMR (100 MHz, acetone-d6) δ 168.4, 163.4 (d, J = 248.3
Hz), 159.0 (d, J = 6.5 Hz), 134.2 (d, J = 3.6 Hz), 132.3 (d, J = 11.7
Hz), 122.8 (d, J = 8.8 Hz), 112.8 (d, J = 2.9 Hz), 111.4 (d, J = 13.5
Hz), 107.5 (d, J = 22.9 Hz); HRMS (ESI) m/z [M + H]+ calcd for
C9H8FO3 183.0452, found 183.0451.
CONCLUSION
■
An efficient strategy has been developed for constructing 2-
sulfonylbenzo[b]furans induced by the CuCl2·2H2O/AgTFA
system using readily available trans-2-hydroxycinnamic acids
and sodium sulfinates as starting materials. The reaction
proceeds via a protodecarboxylation/C−S bond formation/C−
O bond formation cascade. This one-step protocol could
complement the traditional methods for the preparation of 2-
sulfonylbenzo[b]furans. Meanwhile, further applications of this
method to the synthesis of other heterocycles are underway.
(E)-3-(4-Fluoro-2-hydroxyphenyl)acrylic Acid (1h). Recrystalliza-
tion from MeOH/H2O; light-red solid, 663 mg (73%), mp 199−201
1
°C; H NMR (400 MHz, acetone-d6) δ 9.61 (br s, 1H), 7.95 (d, J =
16.0 Hz, 1H), 7.67 (dd, J = 8.8 Hz, 1H), 6.67−6.75 (m, 2H), 6.57 (d, J
= 16.0 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ 168.5, 165.3 (d, J
= 247.0 Hz), 158.9 (d, J = 11.2 Hz), 140.1, 131.5 (d, J = 10.6 Hz),
119.3 (d, J = 3.0 Hz), 118.5 (d, J = 2.2 Hz), 108.0 (d, J = 22.0 Hz),
104.0 (d, J = 24.0 Hz); HRMS (ESI) m/z [M + H]+ calcd for
C9H8FO3 183.0452, found 183.0450.
(E)-3-(5-Chloro-2-hydroxyphenyl)acrylic Acid (1i). Recrystalliza-
tion from MeOH/H2O; yellow solid, 652 mg (66%), mp 217−219 °C;
1H NMR (400 MHz, acetone-d6) δ 9.38 (s, 1H), 7.93 (d, J = 16.4 Hz,
1H), 7.64 (d, J = 2.8 Hz, 1H), 7.25 (dd, J = 8.8, 2.8 Hz, 1H), 6.99 (d, J
= 8.8 Hz, 1H), 6.66 (d, J = 16.4 Hz, 1H); 13C NMR (100 MHz,
acetone-d6) δ 168.0, 156.0, 139.5, 131.7, 128.9, 125.2, 124.1, 120.4,
118.6; HRMS (ESI) m/z [M + H]+ calcd for C9H8ClO3 199.0157,
found 199.0154.
EXPERIMENTAL SECTION
■
General. All reagents and solvents of commercial grade were used
without further purification. Melting points were performed with a
micromelting point apparatus without correction. With CDCl3,
acetone-d6, and DMSO-d6 as solvents, 1H NMR and 13C NMR
spectra were recorded at 400 and 100 MHz, respectively. HRMS was
carried out using electrospray ionization (ESI) as the ion source (linear
ion trap Orbitrap). trans-2-Hydroxycinnamic acid (1a) and the
substituted sulfinic acid sodium salts 2a, 2f, 2j, 2m, and 2n were
commercially available.
Preparation of trans-2-Hydroxycinnamic Acids. These acids
(1b−k) were synthesized starting from substituted salicylaldehydes (5
mmol) according to the literature procedure29 with the exception that
EtOH was used as the solvent.
(E)-3-(3,5-Dichloro-2-hydroxyphenyl)acrylic Acid (1j). Recrystalli-
zation from acetone/H2O; yellow solid, 676 mg (58%), mp 213−215
1
°C; H NMR (400 MHz, DMSO-d6) δ 12.46 (br s, 1H), 10.24 (s,
(E)-3-(2-Hydroxynaphthalen-1-yl)acrylic Acid (1b). Recrystalliza-
1H), 7.78 (d, J = 16.0 Hz, 1H), 7.71 (d, J = 2.4 Hz, 1H), 7.53 (d, J =
2.4 Hz, 1H), 6.61 (d, J = 16.4 Hz, 1H); 13C NMR (100 MHz, DMSO-
d6) δ 167.5, 150.6, 137.2, 130.2, 126.4, 125.6, 124.0, 122.9, 121.6;
HRMS (ESI) m/z [M + H]+ calcd for C9H7Cl2O3 232.9767, found
232.9765.
(E)-3-(5-Bromo-2-hydroxyphenyl)acrylic Acid (1k). Recrystalliza-
tion from acetone/H2O; yellow solid, 623 mg (51%), mp 215−217
°C; 1H NMR (400 MHz, acetone-d6) δ 9.44 (s, 1H), 7.92 (d, J = 16.0
Hz, 1H), 7.77 (d, J = 2.4 Hz, 1H), 7.37 (dd, J = 8.8, 2.4 Hz, 1H), 6.95
(d, J = 8.8 Hz, 1H), 6.66 (d, J = 16.4 Hz, 1H); 13C NMR (100 MHz,
acetone-d6) δ 168.1, 156.5, 139.4, 134.6, 131.9, 124.7, 120.4, 119.0,
112.3; HRMS (ESI) m/z [M + H]+ calcd for C9H8BrO3 242.9651,
found 242.9650.
Preparation of Sodium Sulfinates. Sodium sulfinates 2b−e, 2g−
i, 2k, and 2l were prepared according to the literature procedure.33
General Procedure for the Synthesis of 2-Sulfonylbenzo[b]-
furans. trans-2-Hydroxycinnamic acid (1a) (1 mmol, 164.2 mg), p-
toluenesulfinic acid sodium salt tetrahydrate (2a) (1.2 mmol, 300.3
mg), CuCl2·2H2O (0.5 mmol, 85.2 mg), AgTFA (2.5 mmol, 552.2
mg), and Cs2CO3 (2 mmol, 651.6 mg) were dissolved in 6 mL of
DMF. The mixture was then stirred at 80 °C for 18 h under ambient
atmosphere. After completion of the reaction, the reaction mixture was
cooled to room temperature. DMF was removed under reduced
pressure, and the residue was purified by silica gel column
chromatography using petroleum ether/ethyl acetate (25:1) as the
eluent followed by recrystallization in n-hexane to afford the product
3aa.
tion from EtOH/H2O; yellow solid, 611 mg (57%), mp 186−188 °C
(lit.29 188−189 °C); H NMR (400 MHz, acetone-d6) δ 10.74 (br s,
1
1H), 9.49 (s, 1H), 8.41 (d, J = 16.0 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H),
7.84 (d, J = 8.8 Hz, 2H), 7.57 (dt, J = 7.2, 1.6 Hz, 1H), 7.38 (dt, J =
7.6, 0.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 6.94 (d, J = 16.0 Hz, 1H);
13C NMR (100 MHz, acetone-d6) δ 168.9, 156.3, 138.4, 134.1, 132.5,
129.7, 129.6, 128.3, 124.2, 123.33, 123.25, 119.1, 114.1; HRMS (ESI)
m/z [M + H]+ calcd for C13H11O3 215.0703, found 215.0698.
(E)-3-(2-Hydroxy-6-methoxyphenyl)acrylic Acid (1c). Recrystalli-
zation from MeOH/H2O; light-red solid, 713 mg (73%), mp 186−188
°C; 1H NMR (400 MHz, acetone-d6) δ 9.18 (s, 1H), 8.20 (d, J = 16.4
Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H), 6.94 (d, J = 16.4 Hz, 1H), 6.56−6.61
(m, 2H), 3.89 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 169.8,
161.2, 159.1, 137.0, 132.2, 120.7, 111.6, 109.5, 103.4, 56.1; HRMS
(ESI) m/z [M + H]+ calcd for C10H11O4 195.0652, found 195.0648.
(E)-3-(2-Hydroxy-4-methoxyphenyl)acrylic Acid (1d). Recrystalli-
zation from MeOH/H2O; light-red solid, 596 mg (61%), mp 239−241
°C (lit.29 240−242 °C); H NMR (400 MHz, acetone-d6) δ 9.21 (s,
1
1H), 7.95 (d, J = 16.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 6.45−6.52
(m, 3H), 3.79 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 168.7,
163.6, 158.8, 141.1, 131.1, 116.0, 115.6, 107.2, 102.3, 55.7; HRMS
(ESI) m/z [M + H]+ calcd for C10H11O4 195.0652, found 195.0649.
(E)-3-(2-Hydroxy-5-methylphenyl)acrylic Acid (1e). Recrystalliza-
tion from MeOH/H2O; light-yellow solid, 425 mg (48%), mp 184−
186 °C; 1H NMR (400 MHz, acetone-d6) δ 8.83 (s, 1H), 8.00 (d, J =
16.0 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.06 (dd, J = 8.4, 1.6 Hz, 1H),
6.86 (d, J = 8.4 Hz, 1H), 6.59 (d, J = 16.0 Hz, 1H), 2.25 (s, 3H); 13C
NMR (100 MHz, acetone-d6) δ 168.6, 155.3, 141.3, 133.0, 129.8,
122.0, 118.4, 116.9, 20.4; HRMS (ESI) m/z [M + H]+ calcd for
C10H11O3 179.0703, found 179.0699.
2-[(4-Methylphenyl)sulfonyl]benzofuran (3aa). White solid, 215
mg (79%), mp 95−97 °C (lit.4b 95−96 °C); H NMR (400 MHz,
1
CDCl3) δ 7.96 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.53 (s,
1H), 7.49 (d, J = 8.8 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0
Hz, 2H), 7.30 (t, J = 7.6 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 156.3, 152.0, 145.3, 136.4, 130.0, 128.3, 127.9, 126.0, 124.2,
123.1, 112.9, 112.4, 21.7; HRMS (ESI) m/z [M + H]+ calcd for
C15H13O3S 273.0580, found 273.0576.
(E)-3-(4-Benzyloxy-2-hydroxyphenyl)acrylic Acid (1f). 1f was
prepared by monobenzylation of 2,4-dihydroxybenzaldehyde32 fol-
lowed by Horner−Wittig reaction. Recrystallization from EtOH/H2O;
1
light-yellow solid, 757 mg (56%), mp 188−190 °C; H NMR (400
MHz, acetone-d6) δ 10.44 (br s, 1H), 9.15 (s, 1H), 7.94 (d, J = 16.0
Hz, 1H), 7.32−7.56 (m, 6H), 6.60−6.62 (m, 2H), 6.47 (d, J = 16.0
Hz, 1H), 5.13 (s, 2H); 13C NMR (100 MHz, acetone-d6) δ 168.7,
162.7, 158.9, 141.0, 138.0, 131.1, 129.4, 128.8, 128.5, 116.2, 115.9,
108.1, 103.3, 70.6; HRMS (ESI) m/z [M + H]+ calcd for C16H15O4
271.0965, found 271.0960.
2-[(3-Methylphenyl)sulfonyl]benzofuran (3ab). White solid, 191
mg (70%), mp 116−118 °C; 1H NMR (400 MHz, acetone-d6) δ
7.88−7.90 (m, 2H), 7.82 (d, J = 7.6 Hz, 1H), 7.76 (s, 1H), 7.50−7.61
(m, 4H), 7.38 (t, J = 8.0 Hz, 1H), 2.44 (s, 3H); 13C NMR (100 MHz,
acetone-d6) δ 157.2, 153.0, 141.0, 140.5, 135.9, 130.4, 129.2, 129.0,
127.0, 126.1, 125.4, 124.4, 114.3, 113.0, 21.2; HRMS (ESI) m/z [M +
H]+ calcd for C15H13O3S 273.0580, found 273.0577.
(E)-3-(2-Fluoro-6-hydroxyphenyl)acrylic Acid (1g). Recrystalliza-
tion from MeOH/H2O; light-red solid, 576 mg (63%), mp 191−193
E
dx.doi.org/10.1021/jo4024478 | J. Org. Chem. XXXX, XXX, XXX−XXX

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2-[(2-Methylphenyl)sulfonyl]benzofuran (3ac). White solid, 103
mg (38%), mp 97−99 °C; 1H NMR (400 MHz, acetone-d6) δ 7.96 (d,
J = 8.0 Hz, 2H), 7.82 (d, J = 7.6 Hz, 1H), 7.74 (s, 1H), 7.60 (d, J = 8.4
Hz, 1H), 7.48−7.54 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H), 2.43 (s, 3H);
13C NMR (100 MHz, acetone-d6) δ 157.1, 153.2, 146.5, 137.7, 131.1,
129.1, 129.0, 127.1, 125.3, 124.4, 114.0, 113.0, 21.6; HRMS (ESI) m/z
[M + H]+ calcd for C15H13O3S 273.0580, found 273.0577.
2-[(4-Methoxyphenyl)sulfonyl]benzofuran (3ad). White solid, 222
mg (77%), mp 78−80 °C; 1H NMR (400 MHz, acetone-d6) δ 8.02 (d,
J = 8.4 Hz, 2H), 7.81 (d, J = 7.6 Hz, 1H), 7.68 (s, 1H), 7.59 (d, J = 8.4
Hz, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 7.2 Hz, 1H), 7.17 (d, J =
8.4 Hz, 2H), 3.91 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 165.3,
157.1, 153.7, 131.8, 131.4, 129.0, 127.1, 125.3, 124.3, 115.8, 113.4,
112.9, 56.3; HRMS (ESI) m/z [M + H]+ calcd for C15H13O4S
289.0529, found 289.0526.
2-[(4-(tert-Butyl)phenyl)sulfonyl]benzofuran (3ae). Light-yellow
solid, 204 mg (65%), mp 155−157 °C; 1H NMR (400 MHz,
acetone-d6) δ 8.01 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 1H), 7.75
(s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.52 (t, J =
7.2 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 1.32 (s, 9H); 13C NMR (100
MHz, acetone-d6) δ 159.1, 157.2, 153.2, 137.7, 129.1, 128.9, 127.6,
127.1, 125.4, 124.4, 114.1, 113.0, 35.9, 31.2; HRMS (ESI) m/z [M +
H]+ calcd for C18H19O3S 315.1049, found 315.1048.
2-(Phenylsulfonyl)benzofuran (3af). Light-yellow solid, 155 mg
(60%), mp 121−123 °C; 1H NMR (400 MHz, acetone-d6) δ 8.10 (d, J
= 7.2 Hz, 2H), 7.84 (d, J = 8.0 Hz, 1H), 7.75−7.79 (m, 2H), 7.70 (t, J
= 8.0 Hz, 2H), 7.61 (dd, J = 8.4, 0.8 Hz, 1H), 7.53 (dt, J = 7.2, 1.2 Hz,
1H), 7.39 (dt, J = 8.0, 0.8 Hz, 1H); 13C NMR (100 MHz, acetone-d6)
δ 157.2, 152.9, 140.6, 135.3, 130.6, 129.2, 128.9, 127.0, 125.4, 124.4,
114.5, 113.0; HRMS (ESI) m/z [M + H]+ calcd for C14H11O3S
259.0423, found 259.0421.
157.5, 151.7, 144.4, 135.8 (q, J = 32.6 Hz), 129.9, 129.6, 127.8 (q, J =
3.7 Hz), 126.9, 125.6, 124.6, 124.3 (d, J = 270.8 Hz), 115.7, 113.1;
HRMS (ESI) m/z [M + H]+ calcd for C15H10F3O3S 327.0297, found
327.0301.
N-[4-(Benzofuran-2-ylsulfonyl)phenyl]acetamide (3al). White
solid, 227 mg (72%), mp 179−181 °C; 1H NMR (400 MHz,
acetone-d6) δ 9.62 (s, 1H), 8.00 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 9.2
Hz, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.70 (s, 1H), 7.60 (d, J = 8.4 Hz,
1H), 7.52 (dt, J = 7.2, 0.8 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 2.12 (s,
3H); 13C NMR (100 MHz, acetone-d6) δ 169.7, 157.1, 153.5, 145.9,
133.9, 130.3, 129.0, 127.1, 125.3, 124.3, 119.9, 113.6, 113.0, 24.4;
HRMS (ESI) m/z [M + H]+ calcd for C16H14NO4S 316.0638, found
316.0637.
2-(Methylsulfonyl)benzofuran (3am). Light-yellow solid, 141 mg
(72%), mp 69−71 °C; 1H NMR (400 MHz, acetone-d6) δ 7.86 (d, J =
8.0 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.64 (s, 1H), 7.59 (t, J = 7.6 Hz,
1H), 7.43 (t, J = 7.6 Hz, 1H), 3.34 (s, 3H); 13C NMR (100 MHz,
acetone-d6) δ 156.9, 152.9, 129.1, 127.0, 125.3, 124.4, 113.6, 113.1,
43.3; HRMS (ESI) m/z [M + H]+ calcd for C9H9O3S 197.0267, found
197.0268.
2-[(4-Methylphenyl)sulfonyl]naphtho[2,1-b]furan (3ba). Light-
1
yellow solid, 261 mg (81%), mp 150−152 °C; H NMR (400 MHz,
acetone-d6) δ 8.43 (d, J = 8.0 Hz, 1H), 8.36 (s, 1H), 7.98−8.07 (m,
4H), 7.71 (t, J = 8.0 Hz, 2H), 7.60 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 8.0
Hz, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 155.5,
152.3, 146.4, 138.0, 131.6, 131.1, 130.7, 129.9, 128.88, 128.85, 128.5,
126.7, 124.5, 122.8, 113.4, 113.1, 21.5; HRMS (ESI) m/z [M + H]+
calcd for C19H15O3S 323.0736, found 323.0737.
4-Methoxy-2-[(4-methylphenyl)sulfonyl]benzofuran (3ca). Light-
1
yellow solid, 172 mg (57%), mp 152−154 °C; H NMR (400 MHz,
acetone-d6) δ 7.96 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.43−7.49 (m,
3H), 7.16 (d, J = 8.8 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 3.98 (s, 3H),
2.43 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 158.2, 155.8, 151.9,
146.4, 137.8, 131.1, 130.4, 129.0, 117.5, 111.4, 105.5, 105.4, 56.4, 21.5;
HRMS (ESI) m/z [M + H]+ calcd for C16H15O4S 303.0686, found
303.0682.
2-(Naphthalen-2-ylsulfonyl)benzofuran (3ag). White solid, 160
mg (52%), mp 158−160 °C; 1H NMR (400 MHz, acetone-d6) δ 8.77
(s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.04 (t, J =
7.6 Hz, 2H), 7.70−7.84 (m, 4H), 7.58 (d, J = 8.4 Hz, 1H), 7.51 (dt, J =
8.4, 1.2 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
acetone-d6) δ 157.2, 152.9, 137.5, 136.4, 133.2, 130.9, 130.8, 130.6,
130.5, 129.2, 128.93, 128.86, 127.1, 125.4, 124.4, 123.5, 114.6, 113.0;
HRMS (ESI) m/z [M + H]+ calcd for C18H13O3S 309.0580, found
309.0578.
2-(Ethylsulfonyl)-4-methoxybenzofuran (3cn).3g Light-yellow
1
solid, 75 mg (31%), mp 63−65 °C; H NMR (400 MHz, acetone-
d6) δ 7.57 (s, 1H), 7.52 (t, J = 8.4 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H),
6.93 (d, J = 8.0 Hz, 1H), 4.01 (s, 3H), 3.40 (q, J = 7.2 Hz, 2H), 1.30 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, acetone-d6) δ 158.3, 155.9,
149.9, 130.4, 117.4, 112.5, 105.58, 105.52, 56.4, 50.1, 7.5; HRMS
(ESI) m/z [M + H]+ calcd for C11H13O4S 241.0529, found 241.0526.
6-Methoxy-2-[(4-methylphenyl)sulfonyl]benzofuran (3da). White
solid, 187 mg (62%), mp 96−98 °C; 1H NMR (400 MHz, acetone-d6)
δ 7.93 (d, J = 8.4 Hz, 2H), 7.65−7.68 (m, 2H), 7.47 (d, J = 8.0 Hz,
2H), 7.14 (s, 1H), 6.98 (dd, J = 8.4, 1.6 Hz, 1H), 3.86 (s, 3H), 2.42 (s,
3H); 13C NMR (100 MHz, acetone-d6) δ 161.9, 158.7, 151.8, 146.2,
138.1, 131.0, 128.8, 124.5, 120.0, 115.5, 114.4, 96.4, 56.2, 21.5; HRMS
(ESI) m/z [M + H]+ calcd for C16H15O4S 303.0686, found 303.0682.
5-Methyl-2-[(4-methylphenyl)sulfonyl]benzofuran (3ea). White
solid, 157 mg (55%), mp 116−118 °C; 1H NMR (400 MHz,
acetone-d6) δ 7.95 (d, J = 8.0 Hz, 2H), 7.65 (s, 1H), 7.58 (s, 1H),
7.45−7.49 (m, 3H), 7.33 (d, J = 8.0 Hz, 1H), 2.42 (s, 6H); 13C NMR
(100 MHz, acetone-d6) δ 155.7, 153.2, 146.4, 137.8, 135.0, 131.1,
130.5, 128.9, 127.1, 123.7, 113.7, 112.5, 21.5, 21.2; HRMS (ESI) m/z
[M + H]+ calcd for C16H15O3S 287.0736, found 287.0732.
2-[(4-Fluorophenyl)sulfonyl]benzofuran (3ah). Light-yellow solid,
1
155 mg (56%), mp 96−98 °C; H NMR (400 MHz, acetone-d6) δ
8.15−8.20 (m, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.62 (dd, J
= 8.4, 0.8 Hz, 1H), 7.54 (dt, J = 7.2, 1.6 Hz, 1H), 7.47 (t, J = 8.4 Hz,
2H), 7.40 (dt, J = 8.0, 0.8 Hz, 1H); 13C NMR (100 MHz, acetone-d6)
δ 167.0 (d, J = 254.0 Hz), 157.3, 152.6, 136.8 (d, J = 2.0 Hz), 132.2 (d,
J = 10.0 Hz), 129.3, 127.0, 125.5, 124.5, 117.9 (d, J = 23.0 Hz), 114.6,
113.0; HRMS (ESI) m/z [M + H]+ calcd for C14H10FO3S 277.0329,
found 277.0327.
2-[(4-Chlorophenyl)sulfonyl]benzofuran (3ai). White solid, 149
mg (51%), mp 122−124 °C; 1H NMR (400 MHz, acetone-d6) δ 8.10
(d, J = 8.8 Hz, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.81 (s, 1H), 7.73 (d, J =
8.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.40 (t,
J = 7.6 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ 157.3, 152.2,
141.2, 139.3, 130.9, 130.8, 129.4, 127.0, 125.5, 124.5, 114.9, 113.0;
HRMS (ESI) m/z [M + H]+ calcd for C14H10ClO3S 293.0034, found
293.0033.
6-(Benzyloxy)-2-[(4-methylphenyl)sulfonyl]benzofuran (3fa).
Light-yellow solid, 193 mg (51%), mp 95−97 °C; H NMR (400
2-[(4-Bromophenyl)sulfonyl]benzofuran (3aj). White solid, 175
mg (52%), mp 145−147 °C; 1H NMR (400 MHz, acetone-d6) δ 8.02
(d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 7.6 Hz, 1H),
7.81 (s, 1H), 7.62 (dd, J = 8.4, 0.8 Hz, 1H), 7.55 (dt, J = 8.4, 1.2 Hz,
1H), 7.40 (dt, J = 8.0, 0.8 Hz, 1H); 13C NMR (100 MHz, acetone-d6)
δ 157.3, 152.2, 139.8, 133.9, 130.8, 129.9, 129.4, 127.0, 125.5, 124.5,
114.9, 113.1; HRMS (ESI) m/z [M + H]+ calcd for C14H10BrO3S
336.9529, found 336.9531.
2-[(4-(Trifluoromethyl)phenyl)sulfonyl]benzofuran (3ak). White
solid, 144 mg (44%), mp 123−125 °C; 1H NMR (400 MHz, acetone-
d6) δ 8.33 (d, J = 8.0 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H),
7.85 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.56 (t, J = 7.2 Hz,
1H), 7.41 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ
1
MHz, acetone-d6) δ 7.93 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 1H),
7.65 (s, 1H), 7.46−7.50 (m, 4H), 7.31−7.41 (m, 3H), 7.24 (d, J = 2.0
Hz, 1H), 7.09 (dd, J = 8.4, 2.0 Hz, 1H), 5.21 (s, 2H), 2.43 (s, 3H); 13C
NMR (100 MHz, acetone-d6) δ 160.9, 158.5, 152.0, 146.3, 138.1,
137.7, 131.1, 129.4, 128.9, 128.5, 124.6, 120.3, 116.1, 114.3, 97.7, 71.1,
21.5; HRMS (ESI) m/z [M + H]+ calcd for C22H19O4S 379.0999,
found 379.0995.
4-Fluoro-2-[(4-methylphenyl)sulfonyl]benzofuran (3ga). Light-
1
yellow solid, 195 mg (67%), mp 125−127 °C; H NMR (400 MHz,
acetone-d6) δ 7.98 (d, J = 8.0 Hz, 2H), 7.79 (s, 1H), 7.45−7.58 (m,
4H), 7.15 (t, J = 8.8 Hz, 1H), 2.43 (s, 3H). 13C NMR (100 MHz,
F
dx.doi.org/10.1021/jo4024478 | J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
acetone-d6) δ 158.4 (d, J = 8.2 Hz), 157.4 (d, J = 251.2 Hz), 153.6,
146.8, 137.2, 131.2, 130.2 (d, J = 7.8 Hz), 129.1, 116.5 (d, J = 22.3
Hz), 110.6 (d, J = 18.4 Hz), 109.8 (d, J = 1.7 Hz), 109.5 (d, J = 4.5
Hz), 21.6; HRMS (ESI) m/z [M + H]+ calcd for C15H12FO3S
291.0486, found 291.0482.
mL), and extracted with ethyl acetate (30 mL × 4). After the organic
phases were combined, the solution was dried over anhydrous Na2SO4
and concentrated. Purification of the residue by silica gel column
chromatography using ethyl acetate/petroleum ether (1:40) affored 5
1
as a light-yellow oil (65 mg, 54%). H NMR (400 MHz, CDCl3) δ
7.39 (d, J = 7.6 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 6.90−6.95 (m, 2H),
6.79 (d, J = 8.0 Hz, 1H), 5.74 (d, J = 18.0 Hz, 1H), 5.36 (d, J = 11.2
Hz, 1H), 5.03 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.8, 131.5,
128.9, 127.4, 124.8, 120.9, 115.9, 115.8. HRMS (ESI) m/z [M + H]+
calcd for C8H9O 121.0648, found 121.0651.
6-Fluoro-2-[(4-methylphenyl)sulfonyl]benzofuran (3ha). Light-
1
yellow solid, 183 mg (63%), mp 139−141 °C; H NMR (400 MHz,
acetone-d6) δ 7.95 (d, J = 8.0 Hz, 2H), 7.86 (d, J = 8.4 Hz, 1H), 7.75
(s, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 9.2 Hz, 1H), 7.23 (dt, J =
9.6, 1.6 Hz, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ
163.6 (d, J = 244.6 Hz), 157.2 (d, J = 14.0 Hz), 154.0 (d, J = 4.3 Hz),
146.6, 137.5, 131.2, 129.0, 125.6 (d, J = 10.5 Hz), 123.6 (d, J = 1.7
Hz), 114.3, 114.0, 100.6 (d, J = 27.3 Hz), 21.6; HRMS (ESI) m/z [M
+ H]+ calcd for C15H12FO3S 291.0486, found 291.0483.
Preparation of Benzofuran-2-carboxylic Acid (6). The
preparation of 6 was similar to that of 4 except that the eluent was
DCM/MeOH (25:1). Light-yellow solid, 63 mg (39%), mp 194−196
(lit.34 194−195 °C); H NMR (400 MHz, acetone-d6) δ 7.80 (d, J =
1
8.0 Hz, 1H), 7.63−7.66 (m, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.36 (t, J =
7.2 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ 160.3, 156.6, 147.0,
128.5, 128.1, 124.7, 123.9, 114.7, 112.9; HRMS (ESI) m/z [M + H]+
calcd for C9H7O3 163.0390, found 163.0386.
5-Chloro-2-[(4-methylphenyl)sulfonyl]benzofuran (3ia). Light-
1
yellow solid, 181 mg (59%), mp 159−161 °C; H NMR (400 MHz,
acetone-d6) δ 7.96 (d, J = 8.0 Hz, 2H), 7.85 (s, 1H), 7.72 (s, 1H), 7.63
(d, J = 9.2 Hz, 1H), 7.49−7.52 (m, 3H), 2.43 (s, 3H); 13C NMR (100
MHz, acetone-d6) δ 155.5, 154.6, 146.8, 137.2, 131.2, 130.4, 129.2,
129.1, 128.5, 123.7, 114.6, 113.4, 21.6; HRMS (ESI) m/z [M + H]+
calcd for C15H12ClO3S 307.0190, found 307.0188.
ASSOCIATED CONTENT
■
S
* Supporting Information
5-Chloro-2-[(4-fluorophenyl)sulfonyl]benzofuran (3ih). Light-yel-
1
Copies of H and 13C NMR spectra for all compounds. This
1
low solid, 146 mg (47%), mp 146−148 °C; H NMR (400 MHz,
material is available free of charge via the Internet at http://
pubs.acs.org.
acetone-d6) δ 8.18 (dd, J = 8.4, 5.2 Hz, 2H); 7.88 (s, 1H), 7.77 (s,
1H), 7.66 (d, J = 8.8 Hz, 1H), 7.55 (dd, J = 8.8, 1.2 Hz, 1H); 7.48 (t, J
= 8.4 Hz, 2H); 13C NMR (100 MHz, acetone-d6) δ 167.1 (d, J = 254.0
Hz), 155.6, 154.1, 136.4 (d, J = 3.0 Hz), 132.4 (d, J = 10.0 Hz), 130.5,
129.5, 128.5, 123.8, 118.0 (d, J = 23.0 Hz), 114.7, 114.0; HRMS (ESI)
m/z [M + H]+ calcd for C14H9ClFO3S 310.9940, found 310.9936.
5,7-Dichloro-2-[(4-methylphenyl)sulfonyl]benzofuran (3ja). Yel-
low solid, 68 mg (20%), mp 137−139 °C; 1H NMR (400 MHz,
acetone-d6) δ 7.99 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 2.0 Hz, 1H), 7.80
(s, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 2.45 (s,
3H); 13C NMR (100 MHz, acetone-d6) δ 155.4, 151.4, 147.1, 136.9,
131.3, 130.7, 129.7, 129.2, 128.7, 122.9, 118.7, 114.1, 21.6; HRMS
(ESI) m/z [M + H]+ calcd for C15H11Cl2O3S 340.9801, found
340.9798.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gangliu27@tsinghua.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (Grants 91213303 and
81273364).
5-Bromo-2-[(4-methylphenyl)sulfonyl]benzofuran (3ka). Light-
1
yellow solid, 232 mg (66%), mp 166−168 °C; H NMR (400 MHz,
REFERENCES
■
acetone-d6) δ 8.01 (d, J = 1.6 Hz, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.72
(s, 1H), 7.65 (dd, J = 8.8, 2.0 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.50
(d, J = 8.0 Hz, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ
155.9, 154.5, 146.8, 137.2, 131.9, 131.2, 129.13, 129.09, 126.9, 117.8,
115.0, 113.3, 21.6; HRMS (ESI) m/z [M + H]+ calcd for C15H12BrO3S
350.9685, found 350.9681.
(1) (a) Comprehensive Heterocyclic Chemistry III; Katritzky, A. R.,
Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Pergamon
Press: Oxford, U.K., 2008; Vol. 3, pp 571−623. (b) Nicolaou, K. C.;
Hale, C. R. H.; Nilewski, C.; Ioannidou, H. A. Chem. Soc. Rev. 2012,
41, 5185.
(2) For selected reviews of the synthesis of benzofurans, see: (a) Wu,
X. F.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1. (b) van
Otterlo, W. A. L.; de Koning, C. B. Chem. Rev. 2009, 109, 3743.
(c) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644. (d) Ziegert, R.
Preparation of (E)-2-[2-(4-Methylphenyl)sulfonylvinyl]-
phenol (4). A mixture of trans-2-hydroxycinnamic acid (1a) (1
mmol, 164.2 mg), p-toluenesulfinic acid sodium salt tetrahydrate (2a)
(1.2 mmol, 300.3 mg), CuCl2·2H2O (0.1 mmol, 17.0 mg), AgTFA
(2.5 mmol, 552.2 mg), and Cs2CO3 (2 mmol, 651.6 mg) was dissolved
in 6 mL of DMF, and the reaction vessel was then charged three times
with argon. The reaction mixture was stirred at 100 °C for 18 h until
completion of the reaction and then cooled to room temperature. The
mixture was washed with 1 N HCl (40 mL) and then extracted with
ethyl acetate (30 mL × 3). The combined organic phases were dried
over anhydrous Na2SO4 and evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (ethyl
acetate/petroleum ether 1:20 to 1:5) to obtain 4 as a light-yellow solid
(143 mg, 52%, mp 129−131 °C). 1H NMR (400 MHz, acetone-d6) δ
9.31 (s, 1H), 7.89 (d, J = 15.6 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.59
(dd, J = 8.0, 1.6 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.26−7.33 (m, 2H),
6.98 (dd, J = 8.0, 0.8 Hz, 1H), 6.90 (dt, J = 8.0, 0.8 Hz, 1H), 2.42 (s,
3H); 13C NMR (100 MHz, acetone-d6) δ 157.8, 144.9, 140.0, 138.2,
133.1, 131.0, 130.8, 129.2, 128.3, 121.0, 120.6, 117.1, 21.5; HRMS
(ESI) m/z [M + H]+ calcd for C15H15O3S 275.0736, found 275.0731.
Preparation of 2-Vinylphenol (5).12 A mixture of 1a (1 mmol,
164.2 mg), AgTFA (1 mmol, 220.9 mg), and Cs2CO3 (2 mmol, 651.6
mg) was dissolved in 6 mL of DMF. The resulting mixture was then
stirred at 100 °C for 9 h. After completion of the reaction, the reaction
mixture was cooled to room temperature, washed with 1 N HCl (50
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H
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