Copper(I)-catalyzed synthesis of 2,5-disubstituted furans and thiophenes from haloalkynes or 1,3-diynes

Article abstract of DOI:10.1021/jo300692d

A regioselective synthesis of 2,5-disubstituted furans using copper(I) catalyst from haloalkynes in a one-pot procedure has been reported. This chemistry proceeds through the hydration reaction of 1,3-diynes, which can be readily prepared from the coupling reaction of haloalkynes in the presence of CuI. The procedure also can be used for the facile synthesis of 2,5-disubstituted thiophenes.

Full text of DOI:10.1021/jo300692d

Note
pubs.acs.org/joc
Copper(I)-Catalyzed Synthesis of 2,5-Disubstituted Furans and
Thiophenes from Haloalkynes or 1,3-Diynes
Huanfeng Jiang,* Wei Zeng, Yibiao Li, Wanqing Wu, Liangbing Huang, and Wei Fu
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
S
* Supporting Information
ABSTRACT: A regioselective synthesis of 2,5-disubstituted furans using
copper(I) catalyst from haloalkynes in a one-pot procedure has been
reported. This chemistry proceeds through the hydration reaction of 1,3-
diynes, which can be readily prepared from the coupling reaction of
haloalkynes in the presence of CuI. The procedure also can be used for
the facile synthesis of 2,5-disubstituted thiophenes.
ubstituted furans and thiophenes are ubiquitous in
biologically active molecules1 and have also been used as
the catalyst and 1,10-phen as the ligand. To our delight, the
desired furan 3a was obtained in 65% GC yield (Table 1, entry
1). This result prompted us to screen suitable reaction
conditions (Table 1). After solvent evaluation, we found that
DMSO was the best solvent and afforded 3a with 80% GC yield
(entry 2), while other solvents just led to moderate or low
yields (entries 1, 3, and 4). Further investigation revealed that
the base played a critical role for this transformation (entries
5−9). Cs2CO3, K2CO3, and t-BuOK were ineffective and
NaOH just gave moderate yields, while KOH was the best
choice. The amount of KOH was then examined, and the best
result was obtained by using 5.0 equiv of KOH, which gave 3a
in 93% yield (entry 10). The effects of different copper salts
were also studied (entries 10−13). CuI was found to be the
best catalyst, and the yield reached 93% (entry 10).
Under the optimized conditions (Table 1, entry 10), the
reaction was applied to a range of different substrates smoothly
giving the corresponding products with moderate to excellent
yields, and the results are summarized in Table 2. Aromatic
alkynyl bromides with either electron-donating or electron-
withdrawing groups on the benzene ring were able to generate
the corresponding products in excellent yields. The reaction
conditions were compatible with alkyl, alkoxy, trifluoromethyl,
and halogen groups on the benzene ring providing the
corresponding products in good yields (3b−l). Fortunately,
2,5-diheterocyclic furans could be generated in the same way
(3m,n). We also extended this reaction to phenylethynyl iodide
as a substrate and found that the reaction occurred to give 3a in
good yield (Scheme 2).
S
building blocks for both heterocyclic and acyclic compounds.2
Consequently, the synthesis of furans and thiophenes has
attracted extensive interest.3−5 One continuing challenge
among existing preparative methods is general access to the
2,5-disubstituted derivatives. The discovery of new activation
processes and selective transition-metal-catalyzed transforma-
tions of alkyne have significantly contributed to this field
(Scheme 1).6 While these protocols represent stalwart advances
in the preparation of 2,5-disubstituted furans, there are still
opportunities to design methods with more easily accessible
materials and routines.
Compared with noble-metal catalysts, copper-based methods
have obvious economic attractiveness. The simple head-to-head
dimerization of copper-based Glaser coupling is of special
interest as a convenient way to build conjugated C4 units.7 The
salts of copper can operate as Lewis acids activating carbon−
carbon multiple bonds via π-binding and make the σ-complexes
with heteroatoms in the same fashion.8 Lewis acids promoted
hydration of alkynes to carbonyl compounds is one of the most
important and fundamental functional group transformation
methods,9 and the carbonyl compounds via alkyne hydration
can be used as precursors of furans.10 Many metal complexes
have proved to be useful in alkyne hydration catalysis.6d,i,11
However, there are few examples of copper-catalyzed hydration
of alkynes.12 During our study on the cyclization reaction
involving electron-deficient alkynes for synthesis of furans,13 we
recently focused on developing alkynes hydration to construct
furans catalyzed by copper. Herein we report a novel synthesis
of 2,5-disubstituted furans directly from haloalkynes or 1,3-
diynes through sequential one-pot reactions. The procedure
also can be used for the facile synthesis of 2,5-disubstituted
thiophenes.
Compared with oxygen, sulfur proved to be a better match as
a nucleophile for the diaryl/heterocycle diynes. Applying
Na2S·9H2O instead of KOH successfully afforded the
corresponding 2,5-disubstituted thiophenes (Table 3). Opti-
mum reaction conditions were determined after a short
screening. The best reaction conditions used DMF as the
solvent and a lower reaction temperature to 70 °C. In addition,
It has been demonstrated that haloalkynes are useful
materials in organic reactions.14 Recently, our group has
reported several nucleophilic additions, homocoupling reac-
tions, and transition-metal-catalyzed bond formation reactions
of haloalkynes.15 Based on our previous results, we first studied
the reaction of phenylethynyl bromide in DMF using CuI as
Received: April 4, 2012
Published: May 16, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
Scheme 1. Synthetic Approaches to 2,5-Disubstituted Furans
a
Table 1. Optimization of Reaction Conditions
Table 2. Substrate Scope of 2,5-Disubstituted Furans via Cu-
Catalyzed Reaction
a
b
entry
catalyst
solvent
DMF
base (X equiv)
yield (%)
1
2
CuI
KOH (3.0)
KOH (3.0)
KOH (3.0)
KOH (3.0)
K2CO3 (3.0)
Cs2CO3 (3.0)
t-BuOK (3.0)
NaOH (3.0)
KOH (4.0)
KOH (5.0)
KOH (5.0)
KOH (5.0)
KOH (5.0)
65
80
CuI
DMSO
1,4-dioxane
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
3
CuI
21
4
CuI
56
5
CuI
NR
NR
NR
69
6
CuI
7
CuI
8
CuI
9
CuI
85
10
11
12
13
CuI
CuCl
CuBr
CuCl2
93
a
Reactions were carried out using bromoalkynes (0.5 mmol), CuI (5
75
mol %), 1,10-phen (15 mol %), KOH(5 mmol), H2O (4 mmol),
72
b
DMSO (2.5 mL), 80 °C, 6 h. Isolated yields.
NR
a
Reactions were carried out using bromoalkyne (0.5 mmol), Cu salt (5
Scheme 2. Cu-Catalyzed Reaction of Iodoalkyne
mol %), 1,10-phen (15 mol %), H2O (4 mmol), solvent (2.5 mL), 80
°C, 6 h. Determined by GC.
b
the amounts of CuI and 1,10-phen were increased to 15 and 20
mol %, respectively. Excellent regioselectivity was still observed.
Both aromatic alkynyl bromides and heterocycle alkynyl
bromides could generate the corresponding products in
excellent yields. It is noteworthy that α-terthienyl (4e), which
has anthelmintic and insecticidal activities, could be obtained
with 78% yield in this way.
We conjectured that this reaction would occur through a 1,3-
diyne intermediate. As shown in Table 4, we synthesized series
of 1,3-diyne compounds. With 1,3-diynes as starting materials,
the reaction successfully afforded the corresponding 2,5-
disubstituted furans under the standard condtions. Unsym-
metrical products can also be synthesized in this way (3o−
s).The overall yield of 2,5-disubstituted furans are the same
when alkynyl bromides were used as starting material (Table
4).
To gain a mechanistic insight into the process of this
reaction, a series of competition experiments were conducted to
test the effect of water. When anhydrous DMSO without the
addition of water was used, the yield of 3a was low (Scheme 3),
and the major product was 1,4-diphenylbuta-1,3-diyne. On the
basis of previous reports6e,16 and our experimental data, a
plausible reaction mechanism for copper-catalyzed synthesis of
furans and thiophenes is illustrated in Scheme 4. First, the 1,3-
diyne B could be generated from bromoalkyne A via Cu(I)
catalysis. The single alkyne hydration and enol-ketone
equilibrium provided D. Then the nucleophilic attack of
carbonyl oxygen to the copper-coordinated alkyne may result in
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Note
Table 3. Substrate Scope of 2,5-Disubstituted Thiophenes
via Cu-Catalyzed Reaction
Scheme 4. Proposed Mechanism for the Synthesis of 2,5-
Disubstituted Furans
a
a
Reactions were carried out using bromoalkynes (0.5 mmol), CuI (15
mol %), 1,10-Phen (20 mol %), Na2S·9H2O(2.5 mmol), DMF (2.5
b
mL), 70 °C, 6 h. Isolated yields.
easy access to conduct reaction with simple starting material in
high-yielding reactions under mild conditions.
Table 4. Substrate Scope for Cu-catalyzed Reaction of 1,3-
Diynes 2
a
EXPERIMENTAL SECTION
■
1
General Methods. H and 13C NMR spectra were recorded on a
400 MHz spectrometer using CDCl3 as solvent and TMS as an
internal standard. Mass spectra were obtained with a gas chromato-
graph−mass spectrometer.
Typical Procedure for the Synthesis of 2,5-Disubstituted
Furans or Thiophenes. A mixture of phenylethynyl bromide 1 (0.5
mmol), CuI (4.8 mg, 5 mol %), 1,10-phen (13.5 mg, 15 mol %), KOH
(140 mg, 5 equiv), and H2O (7.2 mg, 4 mmol) in DMSO (2.5 mL)
was placed in a test tube (10 mL) equipped with a magnetic stirring
bar. The mixture was stirred at 80 °C for 6 h. After the reaction was
complete, the mixture was filtered through a glass filter and washed
with ethyl acetate. The mixture was washed with brine and extracted
with ethyl acetate. The organic layer was dried (MgSO4), concentrated
in vacuo, and purified by flash silica gel chromatography using
petroleum ether/ethyl acetate 20:1 to give the desired products.
2,5-Diphenylfuran (3a): 51.3 mg, 93%; 1H NMR (400 MHz,
CDCl3) δ = 7.73−7.75 (m, 4H), 7.40 (t, J = 7.6 Hz, 4H), 7.24−7.28
(m, 2H), 6.72 (s, 2H); 13C NMR (100 MHz, CDCl3) δ = 153.4, 130.8,
128.7, 127.4, 123.8, 107.3; MS (EI) m/z 115, 165, 191, 220; IR
νmax(KBr)/cm−1 1475, 1022, 796, 757, 689.
a
Reactions were carried out using 1,3-diynes(0.25 mmol), CuI (5 mol
%), 1,10-Phen (15 mol %), KOH(2.5 mmol), H2O (2 mmol), DMSO
(2.5 mL), 80 °C, 6 h. Isolated yields.
b
Scheme 3. Controlled Experiment
2,5-Di-p-tolylfuran (3b): 55.4 mg, 90%; 1H NMR (400 MHz,
CDCl3) δ = 7.63 (d, J = 8 Hz, 4H), 7.20 (d, J = 8 Hz, 4H), 6.65 (s,
2H), 2.37 (s, 6H); 13C NMR (100 MHz, CDCl3) δ = 153.2, 137.1,
129.4, 128.2, 123.6, 106.4, 21.3; MS (EI) m/z 129, 205, 233, 248; IR
νmax (KBr)/cm−1 2924, 1486, 1022, 822, 791.
1
2,5-Di-m-tolylfuran (3c): 53.9 mg, 87%; H NMR (400 MHz,
CDCl3) δ = 7.54−7.56 (m, 4H), 7.29 (t, J = 7.2 Hz, 2H), 7.08 (d, J = 8
Hz, 2H), 6.70 (s, 2H), 2.41 (s, 6H); 13C NMR (100 MHz, CDCl3) δ =
153.4, 138.3, 130.8, 128.6, 128.2, 124.3, 120.9, 107.1, 21.6; MS (EI)
m/z 119, 129, 205, 248; IR νmax (KBr)/cm−1 2920, 1478, 1026, 782,
697.
1
the formation of the resonance stabilized oxonium ion F, which
could easily transfer to intermediate G. Finally, a rearrangement
took place in which G was converted to furan product H with
regeneration of the Cu(I) catalyst.
In conclusion, we have established a facile and highly
stereoselective method to synthesize 2,5-disubstituted furans
from haloalkynes or 1,3-diynes in the presence of the CuI
catalyst. Furthermore, we have shown that the procedure can
be used for the facile synthesis of 2,5-disubstituted thiophenes.
This approach can tolerate a broad range of aryl and
heterocyclic groups and it is particularly useful as this is an
2,5-Bis(4-ethylphenyl)furan (3d): 62.1 mg, 90%; H NMR (400
MHz, CDCl3) δ = 7.65 (d, J = 8 Hz, 4H), 7.23 (d, J = 8.0 Hz, 4H),
6.66 (s, 2H), 2.66 (q, J = 7.2 Hz, 4H), 1.26 (t, J = 7.2 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ = 153.3, 143.5, 128.5, 128.2, 123.7, 106.5,
28.7, 15.6; MS (EI) m/z 123, 207, 246, 261, 276; IR νmax (KBr)/cm−1
2924, 1362, 1223, 832, 789.
2,5-Bis(4-fluorophenyl)furan (3e): 53.7 mg, 84%; 1H NMR (400
MHz, CDCl3) δ = 7.67−7.70 (m, 4H), 7.07−7.11 (m, 4H), 6.65 (s,
2H); 13C NMR (100 MHz, CDCl3) δ = 162.2 (d, JC,F = 245.6 Hz),
152.5, 127.1 (d, JC,F = 3.3 Hz), 125.4 (d, JC,F = 8.0 Hz), 115.8 (d, JC,F
=
21.8 Hz), 106.9; MS (EI) m/z 95, 123, 133, 227, 256; IR νmax (KBr)/
cm−1 1488, 1231, 1025, 831, 774.
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Note
2,5-Bis(4-chlorophenyl)furan (3f): 61.2 mg, 85%; 1H NMR (400
MHz, CDCl3) δ = 7.63 (d, J = 8 Hz, 4H), 7.35 (d, J = 8 Hz, 4H), 6.70
(s, 2H); 13C NMR (100 MHz, CDCl3) δ = 152.6, 133.2, 129.0, 129.0,
125.0, 107.8; MS (EI) m/z 111, 114, 149, 189, 225, 288; IR νmax
(KBr)/cm−1 1473, 1106, 1020, 831, 791.
162.0 (d, JC,F = 245.3 Hz), 159.1, 153.5, 151.9, 127.3 (d, JC,F = 3.3 Hz),
125.3 (d, JC,F = 7.9 Hz), 125.2, 123.8, 115.7 (d, JC,F = 21.8 Hz), 114.2,
106.7, 105.7, 55.4; MS (EI) m/z 95.0, 123.0, 170.0, 196.0, 225.0,
253.0, 268.0; IR νmax (KBr)/cm−1 2923, 1489, 1253, 1026, 838, 786.
2-(4-Methoxyphenyl)-5-(thiophene-2-yl)furan (3r): 44.8 mg,
1
2,5-Bis(2-chlorophenyl)furan (3g): 54.1 mg, 75%; 1H NMR
(400 MHz, CDCl3) δ = 7.95 (d, J = 8 Hz, 2H), 7.45 (d, J = 8 Hz, 2H),
7.34 (t, J = 7.6 Hz, 2H), 7.25 (s, 2H), 7.21(t, J = 8 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ = 149.7, 130.1, 130.3, 128.9, 128.2, 128.0, 126.9,
113.0; MS (EI) m/z 139, 149, 189, 225, 288; IR νmax (KBr)/cm−1
1597, 1464, 1421, 1026, 747.
70%; H NMR (400 MHz, CDCl3) δ = 7.64 (d, J = 8.8 Hz, 2H),
7.28−7.29 (m, 1H), 7.20−7.21 (m, 1H), 7.02−7.04 (m, 1H), 6.93 (d, J
= 8.8 Hz, 2H), 6.55 (s, 2H), 3.83 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ = 159.2, 153.1, 148.4, 134.0, 127.7, 125.2, 123.8, 123.7,
122.2, 114.2, 107.2, 105.6, 55.4; MS (EI) m/z 128, 152, 184, 213, 241,
25; IR νmax (KBr)/cm−1 2929, 1503, 1250, 1026, 832, 783, 702.
1
2,5-Bis(3-chlorophenyl)furan (3h): 49.0 mg, 68%; 1H NMR
(400 MHz, CDCl3) δ = 7.70 (s, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.32 (t,
J = 7.6 Hz, 2H), 7.22−7.24 (m, 2H), 6.74(s, 2H); 13C NMR (100
MHz, CDCl3) δ = 152.4, 134.8, 132.1, 130.0, 127.5, 123.8, 121.9,
108.4; MS (EI) m/z 111, 139, 149, 189, 225, 252, 288; IR νmax (KBr)/
cm−1 1579, 1470, 1026, 774, 686.
2-(4-Methoxyphenyl)-5-p-tolylfuran (3s): 55.44 mg, 84%; H
NMR (400 MHz, CDCl3) δ = 7.66 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.0
Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 6.64 (d, J
= 3.6 Hz, 1H), 6.57 (d, J = 3.6 Hz, 1H), 3.82 (s, 3H), 2.36 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ = 159.0, 153.1, 153.0, 137.0, 129.4, 128.3,
125.1, 124.0, 123.6, 114.2, 106.5, 105.6, 55.4, 21.3; MS (EI) m/z 91,
152, 178, 221, 249, 264; IR νmax (KBr)/cm−1 2923, 1488, 1250, 1028,
830, 787.
2,5-Bis(4-bromophenyl)furan (3i): 67.1 mg, 71%; 1H NMR (400
MHz, CDCl3) δ = 7.59 (d, J = 8 Hz, 4H), 7.52 (d, J = 8 Hz, 4H), 6.73
(s, 2H); 13C NMR (100 MHz, CDCl3) δ = 152.7, 131.9, 129.5, 125.2,
121.3, 107.9; MS (EI) m/z 114, 157, 189, 269, 378; IR νmax (KBr)/
cm−1 1582, 1401, 1070, 1006, 824, 792.
2,5-Diphenylthiophene (4a): 54.3 mg, 92%; 1H NMR (400
MHz, CDCl3) δ = 7.62 (d, J = 7.6 Hz, 4H), 7.39 (t, J = 7.8 Hz, 4H),
7.26−7.29 (m, 2H); 13C NMR (100 MHz, CDCl3) δ = 143.6, 134.3,
128.9, 127.5, 125.7, 124.0; MS (EI) m/z: 134, 165, 191, 202, 221, 236;
IR νmax (KBr)/cm−1 1452, 1329, 803, 749, 685.
2,5-Bis(4-(trifluoromethyl)phenyl)furan (3j): 65.9 mg, 74%; 1H
NMR (400 MHz, CDCl3) δ = 7.82(d, J = 8.2 Hz, 4H), 7.65(d, J = 8
Hz, 4H), 6.86(s, 2H). 13C NMR (100 MHz, CDCl3) δ = 152.8, 133.4,
129.4(q, JC,F = 32.4 Hz), 125.8(q, JC,F = 3.9 Hz), 124.1(q, JC,F = 270.2
Hz), 123.9, 109.3; MS (EI) m/z 145, 183, 259, 337, 356; IR νmax
(KBr)/cm−1 1614, 1324, 1108, 837, 778.
2,5-Di-p-tolylthiophene (4b): 57.4 mg, 87%; 1H NMR (400
MHz, CDCl3) δ = 7.50 (d, J = 8.0 Hz, 4H), 7.21 (s, 2H), 7.17 (d, J =
7.6 Hz, 4H), 2.35 (s, 6H); 13C NMR (100 MHz, CDCl3) δ = 143.3,
137.3, 131.7, 129.6, 125.5, 123.5, 21.2; MS (EI) m/z 115, 171, 215,
264; IR νmax (KBr)/cm−1 2917, 1457, 1366, 797.
1
2,5-Bis(4-methoxyphenyl)furan (3k): 59.5 mg, 85%; H NMR
2,5-Bis(4-fluorophenyl)thiophene (4c): 50.3 mg, 74%; 1H NMR
(400 MHz, CDCl3) δ = 7.55−7.59 (m, 4H), 7.19 (s, 2H), 7.08 (t, J =
8.4 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ = 162.3 (d, JC,F = 246.0
Hz), 142.5, 130.5 (d, JC,F = 3.4 Hz), 127.3 (d, JC,F = 7.9 Hz), 124.0,
115.9 (d, JC,F = 21.7 Hz); MS (EI) m/z 133, 152, 176, 238, 272; IR
νmax (KBr)/cm−1 1513, 1456, 1408, 1101, 834, 797.
(400 MHz, CDCl3) δ = 7.66 (d, J = 8.8 Hz, 4H), 6.94 (d, J = 8.8 Hz,
4H), 6.57 (s, 2H), 3.84 (s, 6H); 13C NMR (100 MHz, CDCl3) δ =
158.9, 152.8, 125.0, 124.1, 114.2, 105.6, 55.4; MS (EI) m/z 140, 165,
194, 222, 250, 265, 280; IR νmax(KBr)/cm−1 2924, 1601, 1508, 1252,
1043.
2,5-Bis(4-ethoxyphenyl)furan (3l): 54.7 mg, 71%; 1H NMR
(400 MHz, CDCl3) δ = 7.64 (d, J = 8.8 Hz, 4H), 6.92 (d, J = 8.8 Hz,
4H), 6.56 (s, 2H), 4.07 (q, J = 7.2 Hz, 4H), 1.43 (t, J = 6.8 Hz, 6H);
13C NMR (100 MHz, CDCl3) δ = 158.3, 152.8, 125.0, 124.0, 114.7,
105.5, 63.5, 14.8; MS (EI) m/z 165, 194, 223, 251, 279, 308; IR νmax
(KBr)/cm−1 2926, 2856, 1602, 1509, 1253, 1041.
2,5-Bis(4-chlorophenyl)thiophene (4d): 54.0 mg, 71%; 1H
NMR (400 MHz, CDCl3) δ = 7.53 (d, J = 8.4 Hz, 4H), 7.35 (d, J
= 8.4 Hz, 4H), 7.25 (s, 2H); 13C NMR (100 MHz, CDCl3) δ = 142.7,
133.4, 132.6, 129.1, 126.8, 124.4; MS (EI) m/z 114, 155, 168, 189,
234, 304; IR νmax (KBr)/cm−1 1511, 1454, 1105, 828, 799.
1
2,5-Di(thiophene-2-yl)furan (3m): 48.7 mg, 84%; 1H NMR (400
MHz, CDCl3) δ = 7.29−7.30 (m, 2H), 7.21−7.22 (m, 4H), 7.02−7.04
(m, 2H), 6.53 (s, 2H); 13C NMR (100 MHz, CDCl3) δ = 148.6, 133.5,
127.7, 124.2, 122.7, 107.2; MS (EI) m/z 111, 121, 171, 203, 232; IR
νmax (KBr)/cm−1 1509, 1458, 1417, 1002, 793, 697.
α-Terthienyl (4e): 48.4 mg, 78%; H NMR (400 MHz, CDCl3) δ
= 7.16 (d, J = 9.2 Hz, 2H), 7.13 (d, J = 3.6 Hz, 2H), 7.03 (s, 2H), 6.97
(t, J = 4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ = 137.2, 136.3,
127.9, 124.5, 124.4, 123.8; MS (EI) m/z 127, 171, 203, 216, 248; IR
νmax (KBr)/cm−1 1422, 1057, 831, 796, 682.
2,5-Di(pyridin-2-yl)thiophene (4f): 47.0 mg, 79%; 1H NMR
(400 MHz, CDCl3) δ = 8.59 (d, J = 4.8 Hz, 2H), 7.66−7.69 (m, 4H),
7.63 (s, 2H), 7.14−7.17 (m, 2H); 13C NMR (100 MHz, CDCl3) δ =
152.4, 149.6, 146.0, 136.7, 125.7, 122.1, 119.0; MS (EI) m/z 78, 89,
116, 160, 205, 238; IR νmax (KBr)/cm−1 1581, 1458, 1427, 1295, 776.
2,5-Di(pyridin-2-yl)furan (3n): 41.6 mg, 75%; 1H NMR (400
MHz, CDCl3) δ = 8.62−8.63 (m, 2H), 7.84 (d, J = 7.6 Hz, 2H), 7.75
(t, J = 7.6 Hz, 2H), 7.21 (s, 2H), 7.17−7.20 (m, 2H); 13C NMR (100
MHz, CDCl3) δ = 154.1, 149.7, 149.1, 136.7, 122.2, 118.9, 111.1; MS
(EI) m/z 78, 89, 116, 148, 193, 222; IR νmax (KBr)/cm−1 1699, 1579,
1466, 1010, 777.
2-(4-Methoxyphenyl)-5-phenylfuran (3o): 57.5 mg, 92%; 1H
NMR (400 MHz, CDCl3) δ = 7.2 (d, J = 7.2 Hz, 2H), 7.67 (d, J = 8.8
Hz, 2H), 7.38 (t, J = 8.0 Hz, 2H), 7.22−7.26 (m, 1H), 6.93 (d, J = 8.8
Hz, 2H), 6.70 (d, J = 3.6 Hz, 1H), 6.58 (d, J = 3.6 Hz, 1H), 3.83 (s,
3H); 13C NMR (100 MHz, CDCl3) δ = 159.1, 153.5, 152.7, 130.9,
128.7, 127.1, 125.2, 123.9, 123.6, 114.2, 107.2, 105.7, 55.4; MS (EI)
m/z 125, 152, 178, 235, 250; IR νmax (KBr)/cm−1 2929, 1599, 1499,
1250, 1026, 832, 759.
2-(4-Chlorophenyl)-5-(4-methoxyphenyl)furan (3p): 63.9 mg,
90%; 1H NMR (400 MHz, CDCl3) δ = 7.62−7.66 (m, 4H), 7.34 (d, J
= 8.4 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 3.6 Hz, 1H), 6.58
(d, J = 3.6 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ =
159.3, 153.8, 151.6, 132.6, 129.4, 128.9, 125.3, 124.7, 123.7, 114.2,
107.7, 105.7, 55.4; MS (EI) m/z 178, 241, 269, 284; IR νmax (KBr)/
cm−1 2960, 1478, 1363, 1252, 1026, 833, 787.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR of compounds 3a−s and 4a−f. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jianghf@scut.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (20932002), National Basic Research Program of China
(973 Program) (2011CB808600), Guangdong Natural Science
Foundation (10351064101000000), China Postdoctoral Sci-
2-(4-Fluorophenyl)-5-(4-methoxyphenyl)furan (3q): 58.3 mg,
87%; 1H NMR (400 MHz, CDCl3) δ = 7.64−7.70 (m, 4H), 7.08 (t, J
= 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 3.6 Hz, 1H), 6.57
(d, J = 3.6 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ =
5182
dx.doi.org/10.1021/jo300692d | J. Org. Chem. 2012, 77, 5179−5183

The Journal of Organic Chemistry
Note
Jiang, H.; Wang, A.; Yang, S. J. Org. Chem. 2010, 75, 6700−6703.
(d) Chen, Z.; Jiang, H.; Li, Y.; Qi, C. Chem. Commun. 2010, 46, 8049−
8051. (e) Chen, Z.; Li, J.; Jiang, H.; Zhu, S.; Li, Y.; Qi, C. Org. Lett.
2010, 12, 3262−3265.
(16) Patil, N. T.; Wu, H.; Yamamoto, Y. J. Org. Chem. 2005, 70,
4531−4534.
ence Foundation (2011M501318), and the Fundamental
Research Funds for the Central Universities (2012ZB0011)
for financial support.
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