Palladium-catalyzed oxidative cyclization of 3-phenoxyacrylates: An approach to construct substituted benzofurans from phenols

Article abstract of DOI:10.1021/jo200317f

In this paper, a novel and applicable synthesis of benzofurans from commercially available phenols and propiolate through the direct oxidative cyclization has been developed. In the presence of Pd(OAc)₂/PPh ₃ and CF₃CO

Full text of DOI:10.1021/jo200317f

NOTE
pubs.acs.org/joc
Palladium-Catalyzed Oxidative Cyclization of 3-Phenoxyacrylates: An
Approach To Construct Substituted Benzofurans from Phenols
Chengliang Li,† Yicheng Zhang,† Pinhua Li,*,† and Lei Wang*,†,‡
†Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P R China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. China
S Supporting Information
b
ABSTRACT: In this paper, a novel and applicable synthesis of
benzofurans from commercially available phenols and propiolate
through the direct oxidative cyclization has been developed. In the
presence of Pd(OAc)2/PPh3 and CF3CO2Ag, (E)-type 3-phenoxy-
acrylates underwent reaction smoothly to generate the correspond-
ing benzofurans in good yields in benzene at 110 °C under the air
pressure. In addition, this transformation of phenols into benzo-
furans can also be carried out in one pot. The process was simple
and efficient. A tentative mechanism of palladium-catalyzed oxidative cyclization of 3-phenoxyacrylates was proposed.
enzofuran is one of the important structural units and is
widely found in important heterocyclic biological and med-
propiolate in the presence of a catalytic amount of DABCO
(10 mol %) proceeded smoothly in dichloromethane for 15 min
at room temperature to give the desired conjugate addition
products in excellent yields. The 1H NMR spectroscopic analysis
of the crude product showed that the corresponding mixture of a
pair of separable Z- and E-isomers was obtained with a majority
of the E-isomer. Fortunately, the E-isomer could be facilely
isolated by flash chromatography on a silica column. In some
cases, the reaction completely gave the E-isomer.
Initial attempts for the synthesis of benzofurans from (E)-
3-phenoxyacrylates applied the synthetic methods of indoles
with Pd(OAc)2 or FeCl3 used as catalyst.11 However, no desired
benzofuran was obtained. Thus, it is necessary to optimize the
cyclization reaction conditions. At first, the effect of solvents on
the model reaction (ethyl 3-phenoxyacrylate as model substrate)
was examined, and the results are summarized in Table 1. When
the model reaction was carried out in the presence of Pd(OAc)2
(5 mmol %), PPh3 (5 mmol %), and CF3CO2Ag (2.0 equiv), a
significant solvent effect was observed. Among the solvents
tested in Table 1, benzene was found to be the best (Table 1,
entry 1). A good yield of the desired product was also obtained
when chlorobenzene or toluene was used as solvent (Table 1,
entries 2 and 3). However, when the reactions were performed in
1,2-dichloroethane (DCE) and 1,4-dioxane, 47% and 41% yields
of the corresponding products were obtained, respectively
(Table 1, entries 4 and 5). Meanwhile, only a trace amount of
the product was obtained when the reaction was performed in
MeCN or THF (Table 1, entries 6 and 7). Unfortunately, no
desired product was isolated when the reaction was carried out in
B
ical compounds. Many efforts have been made to achieve
efficient preparation of this motif.1 The most powerful tool is
undoubtedly the palladium-catalyzed annulation reaction, in
which prefunctionalized substrates, such as o-alkynyl- or -halo-
phenol, were generally utilized through Heck and Sonagashira
reactions.2 However, to the best of our knowledge, simple
phenols without halogen and alkyne substituents have rarely
been used as starting materials to directly construct those
derivatives.3 Recently, an oxidative Pechmann condensation
reaction of the simple phenols and β-keto esters was developed
by Li, and the reaction could proceed to generate polysubstituted
benzofurans by using iron catalysts in the presence of an oxidant.4
In recent years, transition-metal-catalyzed CꢀH activation
and functionalization for the atom- and step-economical synth-
esis of functional molecules have attracted tremendous attention
in both academia and industry.5 The advantages of this method
are high efficiency, low cost, and environmental friendliness.6
Several transition metals, such as Pd-,7 Rh-,8 Ru-,9 and Fe-
catalyzed10 CꢀH bond activation and functionalization have
been widely developed. Most recently, an efficient synthesis of
functionalized indoles from commercially available anilines by
palladium- and iron-catalyzed intramolecular oxidative cycliza-
tion via direct oxidative CꢀC coupling by the selective activation
of CꢀH bonds has been reported.11 In this paper, we wish to
report a novel and efficient palladium-catalyzed direct CꢀH
functionalization of 3-phenoxyacrylates. The reactions generated
the corresponding benzofurans in good yields.
As the substrates, 3-phenoxyacrylates were readily prepared
through a one-step procedure.12 According to the literature, the
reaction of various phenols with ethyl propiolate and methyl
Received: February 24, 2011
Published: May 04, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200317f J. Org. Chem. 2011, 76, 4692–4696
|

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NOTE
Table 1. Effect of Solvent on the Cyclization Reactiona
Table 2. Effect of Palladium and Ligand on the Reactiona
yieldb (%)
entry
palladium/ligand
Pd(OAc)2
yieldb (%)
entry
solvent/temp (°C)
1
2
50
81
37
53
55
60
58
67
66
68
0
1
2
3
4
5
6
7
benzene/110
chlorobenzene/110
toluene/110
DCE/80
81
75
Pd(OAc)2/PPh3
PdCl2
3
71
4
PdCl2/PPh3
47
5
Pd(MeCN)2Cl2/PPh3
Pd(PPh3)2Cl2
dioxane/100
MeCN/80
41
6
<10
<10
7
Pd(PCy3)2Cl2
THF/70
a Reaction conditions: (E)-ethyl 3-phenoxyacrylate (1.0 mmol), Pd-
(OAc)2 (0.05 mmol), PPh3 (0.05 mmol), CF3CO2Ag (2.0 mmol),
solvent (2.0 mL), under air, 24 h. b Isolated yields.
8
Pd(PPh3)4
9
Pd(OAc)2/PCy3
Pd(OAc)2/dppf
Pd(OAc)2/1,10-phenanthroline
10
11
a Reaction conditions: (E)-ethyl 3-phenoxyacrylate (1.0 mmol), Pd
source (0.05 mmol), ligand if necessary (0.05 mmol), C6H6 (2.0 mL),
CF3CO2Ag (2.0 mmol) at 110 °C, under air, 24 h. b Isolated yields.
N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO),
N-methyl-2-pyrrolidone (NMP), or EtOH.
We next screened the effect of palladium source and ligand on
the cyclization reaction of model substrate by using CF3CO2Ag
(2.0 equiv) as oxidant at 110 °C in benzene, and the results are
summarized in Table 2. The model reaction could be catalyzed by
PdII salts, or Pd0 complexes, such as Pd(OAc)2, PdCl2, Pd-
(PCy3)2Cl2, Pd(MeCN)2Cl2, Pd(PPh3)2Cl2, and Pd(PPh3)4 in
the absence of additional ligand. From Table 2, the reactivity of Pd
catalytic system decreases in the following order for the cyclization
reaction: Pd(OAc)2/PPh3 > Pd(OAc)2/dppf ≈ Pd(PPh3)4 ≈
Pd(OAc)2/PCy3 > Pd(PPh3)2Cl2 ≈ Pd(PCy3)2Cl2 > Pd-
(MeCN)2Cl2/PPh3 ≈ PdCl2/PPh3 > Pd(OAc)2 > PdCl2
(Table 2, entries 1ꢀ10). It is evident that the P-ligand, such as
(C6H5)3P, (C6H11)3P, or 1,10-bis(diphenylphosphino)ferrocene
(DPPF), could accelerate the reaction to a certain extent. However,
N-ligands such as 1,10-phenanthroline could not assist in palladium-
catalyzing the model reaction and, conversely, restrained the
reactivity of catalyst completely (Table 2, entry 11). But, FeCl3
Table 3. Pd(OAc)2-Catalyzed Cyclization Reactionsa
and FeCl3 6H2O failed to catalyze the reaction, even in the
3
presence of PPh3.
A variety of oxidants were examined for their effects on the model
cyclization reaction. To our delight, the model reaction proceeded
smoothly and generated the desired product in 81% yield, repre-
senting one of the best results when 2 equiv of CF3CO2Ag was used
as oxidant. It was found that C6H5I(OAc)2 was inferior and
generated the desired product in 48% yield. Unfortunately, other
oxidants, such as Ag2O, Ag2CO3, CuCl2 2H2O, Cu(OAc)2, 2,3-
3
dichloro-5,6-dicyanobenzoquinone (DDQ), tert-butyl hydroper-
oxide (TBHP), K2S2O8, (t-C4H9O)2, (C6H5COO)2, I2, and O2
were no longer the effective oxidants in this reaction. With respect to
the oxidant loading, 2 equiv of CF3CO2Ag was found to be optimal.
During the course of further optimization of the reaction tem-
perature and time, the reaction was generally completed within
24 h when it was performed at 110 °C using Pd(OAc)2/PPh3
(5 mmol %) and CF3CO2Ag (2.0 equiv) in benzene.
On the basis of the previously optimized reaction conditions,
the scope of this cyclization reaction was evaluated. A variety of
(E)-type 3-phenoxyacrylate derived from phenol or substituted
phenol and ethyl propiolate were examined for the reaction, and
the results are outlined in Table 3. As can be seen from Table 3,
phenol and substituted phenols, with either electron-donating or
a Reaction conditions: (E)-3-phenoxyacrylate (1.0 mmol), Pd(OAc)2
(0.05 mmol), PPh3 (0.05 mmol), CF3CO2Ag (2.0 mmol), C6H6
(2.0 mL) at 110 °C, under air, 24 h. b Isolated yields.
electron-withdrawing groups attached to the benzene rings, were
able to undergo cyclization reaction smoothly and generated the
corresponding products in good yields (Table 3, entries 1ꢀ12).
It is important to note that the palladium-catalyzed cyclization
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NOTE
Scheme 1
Scheme 3. Plausible Mechanism
Scheme 2
3-substituted propiolates catalyzed by DABCO in CH2Cl2 for
1
15 min at room temperature in excellent yields. The H NMR
analysis of the product showed that the corresponding product as
a pair of Z- and E-isomers was obtained with ratios of E/Z in the
range of 90/10 to 55/45.12 We were also pleased to find that the
obtained substrates underwent palladium-catalyzed oxidative
cyclization smoothly to give the corresponding substituted
benzofurans in moderate to good yields (Scheme 2). The
isolated yields of benzofurans with an electron-donating group
at the 2-position were much better than those of benzofurans
with an electron-withdrawing group at the 2-position. This may
be attributed to the E/Z ratios of substrates and electronic factors
of the substituted groups.
A plausible mechanism of the palladium-catalyzed intramole-
cular oxidative cyclization of 3-phenoxyacrylates was proposed in
Scheme 3. The reaction occurs probably involving (1) the
formation of a vinylpalladium intermediate A by the electrophilic
palladation of 1 with Pd(OAc)2 through CꢀH activation of the
vinyl proton with the assistance of PPh3 as ligand and
deprotonation,14,11b,11d (2) the intramolecular electrophilic aro-
matic palladation of A through CꢀH activation of the aromatic
hydrogen and subsequent proton abstraction,15 forming an
intermediate B, (3) the carbonꢀcarbon bond formation via
reductive elimination of B, affording the corresponding benzo-
furan product 2 and palladium(0), and finally, (4) the oxidation
of Pd0 by the oxidant CF3CO2Ag, regenerating the PdII species
to complete this catalytic cycle. It should be noted that the
oxidative cyclization was suppressed by additional base, such as
K2CO3 or Et3N in a dose-dependent manner.
reaction could tolerate ortho-substituted substrates, and the
corresponding products were obtained in moderate to good
yields (Table 3, entries 4, 7, 8, and 10ꢀ12). Fortunately, a
substrate derived from R-naphthalenol and ethyl propiolate
displayed high reactivity under the optimized reaction conditions
and generated the desired products in 82% yield (Table 3, entry
13). In order to expand the scope of propiolate, (E)-methyl
3-phenoxyacrylate derived from phenol or substituted phenol
and methyl propiolate were also surveyed. The results showed
that good yields of the corresponding products were isolated
(Table 3, entries 14ꢀ17). It should be noted that the cyclization
products in entries 3 and 16 were 6-methylbenzofuran-3-car-
boxylates (2c and 2p).
In general, a mixture of a pair of Z- and E-isomers was obtained
from the reaction of phenols and propiolates. We subsequently
investigated (Z)-ethyl 3-phenoxyacrylate, which was prepared
according to the literature, as a starting material to undergo the
oxidative cyclization reaction under the recommended reaction
conditions. Only 32% yield of the desired product was isolated,
and starting material was recovery in 65% yield (Scheme 1). (Z)-
Ethyl 3-phenoxyacrylate could be converted into its (E)-isomer
in 20% yield in benzene at 110 °C for 2 h.13 It is evident that (E)-
isomer favors the reaction, and (Z)-isomer disfavors the reaction.
In addition, a one-pot sequence reaction enables rapid access to
benzofurans from commercially available phenols and propio-
lates. Phenol was reacted with ethyl propiolate at room tempera-
ture in the presence of DABCO in CH2Cl2 for 15 min to give the
corresponding ethyl 3-phenoxyacrylate, which underwent sub-
sequent oxidative cyclization under the standard reaction condi-
tions with additional HAc (0.2 equiv) to give the desired product
2a in 73% yield (Scheme 1).
In conclusion, we have developed an efficient and applicable
method for the synthesis of benzofurans from commercially
available phenols and propiolate. The process was simple, and a
diverse range of benzofurans were generated in good yields.
Moreover, this transformation of phenols into benzofurans can
also be carried out in one pot. The method is an attractive
alternative to Heck and Sonagashira coupling reactions, which
require the use of ortho-halogen-substituted phenols.
’ EXPERIMENTAL SECTION
General Procedure for the Palladium-Catalyzed Cycliza-
tion Reactions. Under air atmosphere, a sealable reaction tube with a
Teflon-coated screw cap equipped with a magnetic stir bar was charged
with(E)-3-phenoxyacrylate (1.0 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol),
PPh3 (13.1 mg, 0.05 mmol), CF3CO2Ag (440 mg, 2.0 mmol), and
C6H6 (2.0 mL). The reaction vessel was placed in an oil bath at
We further investigated the substrates derived from 4-methyl-
phenol with ethyl but-2-ynoate, ethyl 3-phenylpropiolate, and
dimethyl acetylenedicarboxylate (Scheme 2). The substrates
were prepared from the reaction of 4-methylphenol with various
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1
110 °C, and the mixture was stirred for 24 h and then cooled to room
temperature. The solvent was filtered and concentrated under reduced
pressure, and the residue was purified by flash chromatography on silica
gel (eluant: hexane/ethyl acetate) to give the corresponding cyclization
reaction product.
Typical Procedure for the Synthesis of 2a in One Pot. A
Schlenk tube with a magnetic stirring bar was charged with ethyl
propiolate (1.0 mmol), phenol (1.0 mmol), DABCO (0.10 mmol),
and CH2Cl2 (2.0 mL). The reaction mixture was stirred for 15 min at
room temperature, and then the solvent was evaporated under reduced
pressure. Pd(OAc)2 (0.05 mmol), PPh3 (0.05 mmol), CF3CO2Ag
(2.0 mmol), HAc (0.20 mmol), and C6H6 (2.0 mL) was added to the
above Schlenk tube. The reaction vessel was placed in an oil bath at
110 °C, and the mixture was stirred for 24 h, then it was cooled to room
temperature. The solvent was filtered and concentrated under reduced
pressure, and the residue was purified by flash chromatography on silica
gel to give 2a (138 mg, 73% yield).
Ethyl 5-tert-butylbenzofuran-3-carboxylate (2i): H NMR
(400 MHz, CDCl3) δ = 8.23 (s, 1H), 8.10 (s, 1H), 7.47ꢀ7.42 (m, 2H),
4.42 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H), 1.41 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ = 163.6, 153.8, 151.0, 147.3, 124.3, 123.2, 118.0,
114.6, 110.9, 60.4, 34.8, 31.8, 14.3; HRMS (ESI) ([M]þ) calcd for
C15H18O3 246.1256, found 246.1257.
Ethyl 7-phenylbenzofuran-3-carboxylate (2j): 1H NMR
(400 MHz, CDCl3) δ = 8.32 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.82
(d, J = 8.0 Hz, 2H), 7.54ꢀ7.50 (m, 3H), 7.47ꢀ7.42 (m, 2H), 4.45 (q, J =
7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ =
163.4, 152.8, 150.9, 135.7, 128.6, 127.9, 125.9, 125.3, 124.8, 124.7, 121.1,
114.8, 60.6, 14.3; HRMS (ESI) ([M]þ) calcd for C17H14O3 266.0943,
found 226.0940.
Ethyl 5,7-dimethylbenzofuran-3-carboxylate (2k): 1H
NMR (400 MHz, CDCl3) δ = 8.21 (s, 1H), 7.66 (s, 1H), 6.97 (s,
1H), 4.40 (q, J = 7.2 Hz, 2H), 2.48 (s, 3H), 2.44 (s, 3H), 1.42 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.7, 153.2, 150.8,
133.8, 127.5, 124.2, 121.2, 119.0, 114.5, 60.4, 21.3, 14.8, 14.4; HRMS
(ESI) ([M]þ) calcd for C13H14O3 218.0943, found 218.0936.
Ethyl 6,7-dimethylbenzofuran-3-carboxylate (2l): 1H NMR
(400 MHz, CDCl3) δ = 8.19 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.14 (d, J =
8.0 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.38 (s, 3H), 1.41 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.7, 155.2, 150.2,
133.7, 126.2, 121.9, 120.1, 118.4, 114.9, 60.4, 19.1, 14.3, 11.5; HRMS
(ESI) ([M]þ) calcd for C13H14O3 218.0943, found 218.0945.
Ethyl naphtho[1,2-b]furan-3-carboxylate (2m): 1H NMR
(400 MHz, CDCl3) δ = 8.32 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.07
(d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H),
7.60ꢀ7.56 (m, 1H), 7.52ꢀ7.48 (m, 1H), 4.42 (q, J = 8.0 Hz, 2H), 1.43
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.5, 151.2,
149.6, 131.7, 128.3, 126.6, 125.7, 124.7, 121.0, 120.6, 119.8, 119.6, 115.7,
60.5, 14.3; HRMS (ESI) ([M]þ) calcd for C15H12O3 240.0786, found
24.0788.
Cyclization compounds, ethyl benzofuran-3-carboxylate (2a),16
methyl benzofuran-3-carboxylate (2n),17 methyl 5-methylbenzofuran-
3-carboxylate (2o),17 and methyl 6-methylbenzofuran-3-carboxylate
(2p)17 have been previously reported, and their identities were con-
firmed by comparison of their spectral data with reported ones.
Ethyl 5-methylbenzofuran-3-carboxylate (2b): 1H NMR
(400 MHz, CDCl3) δ = 8.20 (s, 1H), 7.85 (s, 1H), 7.38 (d, J =
8.0 Hz, 1H), 7.16ꢀ7.13 (m, 1H), 4.40 (q, J = 7.2 Hz, 2H), 2.47 (s, 3H),
1.41 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.5, 154.0,
151.0, 133.7, 126.4, 124.6, 121.7, 114.3, 111.0, 60.4, 21.3, 14.3; HRMS
(ESI) ([M]þ) calcd for C12H12O3 204.0786, found 204.0784.
Ethyl 6-methylbenzofuran-3-carboxylate (2c): 1H NMR
(400 MHz, CDCl3) δ = 8.18 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.31
(s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 2.47 (s, 3H),
1.41 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.5, 156.0,
150.3, 135.5, 125.5, 122.0, 121.4, 114.5, 111.7, 60.4, 21.6, 14.3; HRMS
(ESI) ([M]þ) calcd for C12H12O3 204.0786, found 204.0783.
Ethyl 7-methylbenzofuran-3-carboxylate (2d): 1H NMR
(400 MHz, CDCl3) δ = 8.24 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.24
(t, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 2.51
(s, 3H), 1.41 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ =
163.5, 154.6, 150.6, 126.0, 124.1, 121.8, 119.3, 114.8, 60.4, 14.8, 14.3;
HRMS (ESI) ([M]þ) calcd for C12H12O3 204.0786, found 204.0785.
1
Methyl 7-methylbenzofuran-3-carboxylate (2q): H NMR
(400 MHz, CDCl3) δ = 8.25 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.25 (t, J =
7.2 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 3.94 (s, 3H), 2.53 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ = 163.8, 154.6, 150.6, 126.0, 124.1, 124.0,
121.8, 119.3, 114.5, 51.4, 14.7; HRMS (ESI) ([M]þ) calcd for
C11H10O3 190.0630, found 190.0629.
Ethyl 2,5-dimethylbenzofuran-3-carboxylate (2r): 1H NMR
(400 MHz, CDCl3) δ = 7.74 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.06 (d, J =
8.4 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 2.73 (s, 3H), 2.45 (s, 3H), 1.44 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.6, 151.9, 133.1,
126.2, 125.3, 121.5, 114.5, 110.1, 108.6, 60.1, 21.4, 14.5, 14.4; HRMS
(ESI) ([M]þ) calcd for C13H14O3 218.0943, found 218.0945.
Methyl 5-methyl-2-phenylbenzofuran-3-carboxylate (2s):
1H NMR (400 MHz, CDCl3) δ = 7.97 (d, J = 6.4 Hz, 2H), 7.77 (s, 1H),
7.41ꢀ7.39 (m, 3H), 7.29 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H),
3.84 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ =
164.2, 160.5, 151.9, 133.2, 129.9, 129.4, 129.1, 127.7, 126.7, 126.2,
122.1, 110.3, 108.1, 51.2, 21.2; HRMS (ESI) ([M]þ) calcd for
C17H14O3 266.0943, found 266.0940.
1
Ethyl 5-methoxybenzofuran-3-carboxylate (2e): H NMR
(400 MHz, CDCl3) δ = 8.21 (s, 1H), 7.52 (s, 1H), 7.40 (d, J = 8.0 Hz,
1H), 6.95 (d, J = 8.0 Hz, 1H), 4.41 (q, J = 7.2 Hz, 2H), 3.88 (s, 3H), 1.41
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 163.5, 156.9,
151.4, 150.5, 125.4, 114.6, 114.4, 112.2, 103.7, 60.4, 55.8, 14.3; HRMS
(ESI) ([M]þ) calcd for C12H12O4 220.0736, found 220.0733.
Ethyl 5-chlorobenzofuran-3-carboxylate (2f): 1H NMR
(400 MHz, CDCl3) δ = 8.26 (s, 1H), 8.03 (s, 1H), 7.45 (d, J =
8.0 Hz, 1H), 7.34ꢀ7.31 (m, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.43 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 162.9, 153.9, 152.0,
130.0, 126.0, 125.6, 121.8, 114.5, 112.7, 60.8, 14.3; HRMS (ESI) ([M]þ)
calcd for C11H9O3Cl 224.0240, found 224.0236.
1
Ethyl 7-chlorobenzofuran-3-carboxylate (2g): 1H NMR
(400 MHz, CDCl3) δ = 8.29 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.36
(d, J = 8.0 Hz, 1H), 7.30 (m, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.42 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 162.8, 151.3, 130.9,
126.3, 125.4, 125.0, 120.6, 117.1, 115.4, 60.8, 14.3; HRMS (ESI) ([M]þ)
calcd for C11H9O3Cl 224.0240, found 224.0238.
Dimethyl 5-methylbenzofuran-2,3-dicarboxylate (2t): H
NMR (400 MHz, CDCl3) δ = 7.65 (s, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.26
(t, J = 8.8 Hz, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 2.43 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ = 163.0, 159.1, 152.6, 145.4, 134.6, 129.7, 125.4,
122.2, 118.0, 111.7, 52.9, 52.5, 21.4; HRMS (ESI) ([M]þ) calcd for
C13H12O5 248.0685, found 248.0683.
Ethyl 5,7-dichlorobenzofuran-3-carboxylate (2h): 1H NMR
(400 MHz, CDCl3) δ = 8.30 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.37 (d, J =
1.6 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ = 162.3, 152.2, 149.9, 130.3, 127.0, 125.6, 120.4,
117.7, 115.2, 61.0, 14.3; HRMS (ESI) ([M]þ) calcd for C11H8O3Cl2
257.9850, found 257.9848.
’ ASSOCIATED CONTENT
Supporting Information. Copies of H and 13C NMR
1
S
b
spectra of all cyclization products. This material is available free
of charge via the Internet at http://pubs.acs.org.
4695
dx.doi.org/10.1021/jo200317f |J. Org. Chem. 2011, 76, 4692–4696

The Journal of Organic Chemistry
NOTE
’ AUTHOR INFORMATION
(13) (a) Al-Ekabi, H.; de Mayo, P. J. Phys. Chem. 1985, 89, 5815. (b)
Kistiakowsky, G. B.; Smith, W. R. J. Am. Chem. Soc. 1936, 58, 2428.
(14) (a) Xu, Y.-H.; Lu, J.; Loh, T.-P. J. Am. Chem. Soc. 2009,
131, 1372. (b) Hatamoto, Y.; Sakaguchi, S.; Ishii, Y. Org. Lett. 2004,
6, 4623. (c) Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 3364.
(15) (a) Echavarren, A. M.; Gꢀomez-Lor, B.; Gonzꢀalez, J. J.; de
Frutos, O. Synlett 2003, 585. (b) Jia, C.; Kitamura, T.; Fujiwara, Y.
Acc. Chem. Res. 2001, 34, 633.
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8, 5661.
(17) Rosa, C. D.; Kneeteman, M. N.; Mancini, P. M. E. Tetrahedron
Corresponding Author
*E-mail: leiwang@chnu.edu.cn; pinhuali@yahoo.com.cn.
ꢀ
’ ACKNOWLEDGMENT
We gratefully acknowledge the financial support by the
National Natural Science Foundation of China (Nos.
21002039 and 20972057).
Lett. 2005, 46, 8711.
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4696
dx.doi.org/10.1021/jo200317f |J. Org. Chem. 2011, 76, 4692–4696