One-pot synthesis of furans using base- and acid-supported reagents Na 2CO3/Al2O3-PPA/SiO2'

Article abstract of DOI:10.1055/s-0030-1258402

A convenient method for the one-pot synthesis of furans from -keto esters and -halo ketones was developed using an acid- and base-supported reagent system Na₂CO₃/Al₂O₃-PPA/SiO₂'. The condensation reaction of triketones, which are formed from the reaction of -keto esters with -halo ketones in the presence of Na₂CO ₃/Al₂O₃, was promoted by PPA/SiO₂ to give the corresponding furans in good yields. This method is simple and easy to perform in comparison with stepwise processes, and the yields are good.

Full text of DOI:10.1055/s-0030-1258402

PAPER
619
One-Pot Synthesis of Furans Using Base- and Acid-Supported Reagents
‘Na2CO3/Al2O3–PPA/SiO2’
O
ne-PotSynthe
a
sisof Fura
d
ns ashi Aoyama,*a,b Takashi Nagaoka,a Toshio Takido,a Mitsuo Kodomaric
a
Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku,
Tokyo 101-8308, Japan
Fax +81(3)32590818; E-mail: aoyama@chem.cst.nihon-u.ac.jp
The Center for Creative Materials Research, Research Institute of Science and Technology, College of Science and Technology,
Nihon University, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
b
c
Department of Bioscience and Engineering, Shibaura Institute of Technology, Fukasaku, Minuma-ku, Saitama 337-8570, Japan
Received 1 November 2010; revised 2 December 2010
arenethiols to give sulfanyl ketones and the condensation
reaction of the sulfanyl ketones to afford arylthio-
phenes.10,11 The process also promotes the following reac-
tions: Michael addition of arenethiols to a,b-unsaturated
Abstract: A convenient method for the one-pot synthesis of furans
from b-keto esters and a-halo ketones was developed using an acid-
and base-supported reagent system ‘Na2CO3/Al2O3–PPA/SiO2’.
The condensation reaction of triketones, which are formed from the
reaction of b-keto esters with a-halo ketones in the presence of aldehyde by Na2CO3/SiO2, and cyclization of the product
by PPA/SiO2 to form thiochromanes in one pot.12 We at-
Na2CO3/Al2O3, was promoted by PPA/SiO2 to give the correspond-
ing furans in good yields. This method is simple and easy to perform
tempted to expand the scope of this process to the one-pot
in comparison with stepwise processes, and the yields are good.
synthesis of furans. In this paper, we describe the one-pot
Key words: furan, one-pot synthesis, supported reagents
synthesis of furans from b-keto esters and a-halo ketones
using Na2CO3/Al2O3–PPA/SiO2. The reaction of ethyl ace-
toacetate (1a) and phenacyl bromide (2a) was employed
Furans and their derivatives are important compounds in as a model reaction for the determination of the optimum
organic chemistry since these structures can be found in reaction conditions. The reaction of 1a with 2a in the pres-
many natural products or therapeutic compounds.1–3 ence of various inorganic solid supported bases afforded
Many synthetic methods have been developed for mono-, 1,4-dicarbonyl compound 3a (Scheme 1). Silica gel sup-
di-, and trisubstituted furans.4 The cyclization reaction of ported sodium carbonate (Na2CO3/SiO2) gave 3a in 60%
1,4-diketones in the presence of an acid is a classical yield, whereas alumina-supported sodium carbonate
method for the synthesis of furans. Various acids, such as (Na2CO3/Al2O3) afforded 3a in 86% yield. Using alumi-
hydrochloric acid, acetic acid, trifluoroacetic acid, and 4- na-supported potassium fluoride (KF/Al2O3) as the base
toluenesulfonic acid, may be used as an acid catalyst for catalyst gave 3a in 84% yield. In this case, a large quantity
this reaction.5,6 Lewis acids, including zinc halides and of KF/Al2O3 was required to obtain 3a in high yield. PPA/
boron trifluoride–diethyl ether complex, have been also SiO2 catalyzed cyclocondensation of 3a to give 4a. In the
used for the synthesis of furans from 1,4-diketones.7 1,4- case of the cyclocondensation of sulfanyl ketones to give
Diketones are usually prepared by the reaction of 1,3-di- arylthiophenes, the catalytic activity of PPA/SiO2 depend-
carbonyl compounds with a-halo ketones in the presence ed on the loading ratio of PPA.11 In contrast, cycloconden-
of a base catalyst. Thus, the preparation of 1,4-diketones sation of 3a was not affected by the loading ratio of PPA
and the cyclization reaction of 1,4-diketones have been onto SiO2. For instance, 4a was obtained in 91% yield
carried out in a stepwise process.8 One-pot synthesis of from the reaction using either PPA/SiO2 (30 wt%) or
furans from 1,3-dicarbonyl compounds and a-halo ke- PPA/SiO2 (10 wt%).
tones has not been reported because both acid and base
We attempted to synthesize 4a in one-pot using Na2CO3/
Al2O3 (1.5 mmol/g) and PPA/SiO2 (30 wt%). As shown in
Table 1, when the reaction of 1a with 2a was carried out
in the presence of Na2CO3/Al2O3 and PPA/SiO2 (30 wt%),
the isolated yield of 4a was 73% (Table 1, entry 4). The
yield of 4a obtained by this method was as good as the
stepwise process. Moreover the total reaction time was re-
catalysts could not co-exist in the same vessel. Recently,
Chochois et al.9 have reported a rapid one-pot furan syn-
thesis via 1,4-carbonylative addition–cyclization reaction.
Previously we developed acid and base co-existence reac-
tions using inorganic solid supported acid and base. The
process promoted a multistep reaction in one-pot without
neutralization of the acid and base. For instance, ‘silica
duced and the handling was simple and easer compared to
gel supported sodium carbonate and silica gel supported
the stepwise process. The reaction did not occur when
polyphosphoric acid (Na2CO3/SiO2–PPA/SiO2)’ pro-
granular Na2CO3 and viscous PPA in toluene were used
motes the substitution reaction of a-halo ketones with
(Table 1, entry 1). When the reaction was carried out in
the presence of Na2CO3/Al2O3 only 3a was obtained and
the cyclocondensation of 3a did not occur (Table 1, entry
2). On the other hand, when the reaction was carried out
SYNTHESIS 2011, No. 4, pp 0619–0625
Advanced online publication: 12.01.2011
x
x
.
x
x
.2
0
1
1
DOI: 10.1055/s-0030-1258402; Art ID: F18910SS
© Georg Thieme Verlag Stuttgart · New York

620
T. Aoyama et al.
PAPER
O
O
O
O
O
OEt
Br
1a
OEt
OEt
O
base/support
80 °C, 2 h
PPA/SiO2
80 °C, 1 h
+
O
Ph
O
Ph
3a
4a
PPA/SiO2 (10 wt% or 30 wt%, 1.0 g): 91%
Ph
Na2CO3/SiO2 (1.5 mmol/g, 2.0 g): 60%
Na2CO3/Al2O3 (1.5 mmol/g, 1.5 g): 86%
KF/Al2O3 (7.4 mmol/g, 1.0 g): 84%
2a
Scheme 1
Table 1 One-Pot Synthesis of 4a Using a Combination of Base and
Acid
bromide was used (Table 2, entry 1). In contrast, when
phenacyl chloride was used instead of phenacyl bromide,
the substitution reaction did not proceed effectively and
4a was obtained in moderate yield (Table 2, entry 2).
Though this reaction was carried out under more severe
conditions, at 110 °C for 24 hours, the yield did not in-
crease satisfactorily. Using phenacyl iodide, deiodination
occurred and acetophenone was formed along with 4a
(Table 2, entry 3). Yields of the corresponding furans de-
creased according to the increasing size of substituent R1
in compound 1 (Table 2, entries 1 and 4–7). On the other
hand, the yields were not affected by the substituent R2 ex-
cept in the case of the tert-butyl group. Any acetoacetic
acid esters except tert-butyl ester gave furans in moderate
yield. The tert-butyl ester afforded the corresponding
furans in low yields because the tert-butyl group is sensi-
tive to acid and is easily hydrolyzed. This one-pot reaction
using the tert-butyl ester was carried out separately. Reac-
tion of tert-butyl acetoacetates with phenacyl bromide in
the presence of KF/Al2O3 was carried out, and then the re-
action mixture was filtered to remove KF/Al2O3. PPA/
SiO2 was added to the filtrate and the mixture was stirred
at 80 °C for one hour; 3-acetyl-2-hydroxy-5-phenylfuran
was obtained in 59% yield. A method for the synthesis of
this compound has been reported by Stauffer et al.6 They
have synthesized this compound using sodium hydride
and trifluoroacetic acid in two steps. Various a-halo ke-
tones were also able converted into furans in moderate to
good yields, but chloroacetone did not give the corre-
sponding furan (Table 2, entries 12–20). sec-a-Halo ke-
tones gave the products in poor yields. In this reaction, the
first step, C-alkylation, did not proceed successfully.
O
OEt
O
O
O
Na2CO3/Al2O3–PPA/SiO2
Br
+
OEt Ph
toluene
Ph
O
4a
80 °C, 2 h
1a
2a
O
O
OEt
O
PPA/SiO2
Na2CO3/Al2O3
Ph
3a
Entry
Reagent system
Yielda (%)
Base
Acid
PPA
none
3a
4a
0
1
2
3
4
Na2CO3
no reaction
b
b
Na2CO3/Al2O3
none
86
c
c
PPA/SiO2
PPA/SiO2
no reaction
0
Na2CO3/Al2O3
73
a Isolated yield.
b Na2CO3/Al2O3 (1.5 mmol/g, 1.5g).
c PPA/SiO2 (30 wt%, 1.0g).
in the presence of PPA/SiO2, starting materials 1a and 2a
were recovered quantitatively.
Some dicarbonyl compounds and a-halo ketones were
used in this one-pot reaction and the results are summa-
rized in Table 2. In the reactions of 1a with phenacyl ha-
lides, 4a was obtained in good yield when phenacyl
Table 2 One-Pot Synthesis of Furans Using Various b-Keto Esters and a-Halo Ketones
O
OR2
R1
O
O
O
R4
Na2CO3/Al2O3–PPA/SiO2
+
X
R1
OR2
R3
toluene
80 °C, 2 h
R3
R4
O
1
2
4
Entry
R1
R2
Et
Et
Et
R3
Ph
Ph
Ph
R4
X
Product
4a
Yielda (%)
73
1
2
3
Me
Me
Me
H
H
H
Br
Cl
I
4a
34 (47)b
38
4a
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Furans
621
Table 2 One-Pot Synthesis of Furans Using Various b-Keto Esters and a-Halo Ketones (continued)
O
OR2
R1
O
O
O
R4
Na2CO3/Al2O3–PPA/SiO2
+
X
R1
OR2
R3
toluene
80 °C, 2 h
R3
R4
O
1
2
4
Entry
4
R1
Pr
R2
Et
R3
Ph
Ph
Ph
Ph
Ph
Ph
R4
X
Product
4b
4c
Yielda (%)
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Ph
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Br
Br
35 (47)c
27
5
(CH2)6Me
Bn
Et
6
Et
4d
4e
17
7
Ph
Et
8 (43)d
70
8
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Bn
allyl
4f
9
4g
4h
4i
76
10
11
12
13
14
15
16
17
18
19
20
21
22
(CH2)2OMe
Ph
62
t-Bu
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Ph
3
4-ClC6H4
4-MeOC6H4
4-MeC6H4
3-MeC6H4
2-MeC6H4
1-naphthyl
2-naphthyl
t-Bu
4j
56
4k
4l
77
75
4m
4n
4o
4p
4q
4r
59
38
38
73
21
Me
0
Ph
4s
14
Ph
4t
0
a Isolated yield.
b 110 °C, 24 h.
c 110 °C, 1 h.
d 110 °C, 2 h.
When various b-diketones were used instead of b-keto es- polyphosphoric acid (PPA) and various inorganic-sup-
ters for this reaction, the corresponding furans were ob- ported acids. PPA/Bentonite was the most effective
tained in good yields (Table 3). The reaction of 1,3- among the inorganic supported-acids tested and gave
diphenylpropane-1,3-dione required high temperatures compound 6f selectively (Table 4).
and a long reaction time to obtain the product 6c in 47%
In conclusion we have developed a simple and efficient
yield (Table 3, entry 3). The reaction of cyclohexane-1,3-
method for the one-pot synthesis of furans from 1,3-dike-
diones were carried out at 110 °C to afford the corre-
tones and a-halo ketones using Na2CO3/Al2O3–PPA/SiO2.
This procedure has easy handling compared to the step-
wise process and the yields are at least as good as those of
the stepwise procedure. The reaction time was shorter
sponding dihydrobenzofuran-4-ones 6d and 6e in moder-
ate yields along with the regioisomers 6d¢ and 6e¢,
respectively (Table 3, entries 4 and 5). Asymmetric b-
diketone, 1-phenylbutane-1,3-dione, gave 3-benzoyl-2-
than for the stepwise process. Many combinations of 1,3-
methyl-5-phenylfuran (6f) and 3-acetyl-2,5-diphenylfu-
diketones and a-halo ketones produced the corresponding
furans in moderate to good yields. The use of PPA/Bento-
nite instead of PPA/SiO2 increased the yield of 6f, and an
examination of these selective reactions is now under in-
ran (6f¢) in 57% and 20% yields, respectively (Table 3, en-
try 6). When this reaction was carried out using PPA/
Bentonite instead of PPA/SiO2, the yield of 6f increased
to 67% and the yield of 6f¢ decreased to 12%. Cyclocon-
densation reaction of 7 was carried out using viscous
vestigation.
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York

622
T. Aoyama et al.
PAPER
Table 3 Reaction of 2a and Various Diketones
O
O
O
O
R2
Na2CO3/Al2O3–PPA/SiO2
toluene
+
Br
R1
R2
Ph
R1
Ph
O
5
2a
6
Entry
R1
R2
Temp (°C)
Time (h)
Product
6a
Yielda (%)
79
1
2
3
4
5
6
7e
Me
Et
Me
Et
80
80
2
2
6b
58
Ph
Ph
110
110
110
80
24
24
3
6c
47
CH2CMe2CH2
CH2CH2CH2
Me
6d
51 (18)b
38 (10)c
57 (20)d
67 (12)d
6e
Ph
Ph
2
6f
Me
80
2
6f
a Isolated yield.
b Yield of 6,6-dimethyl-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6d¢).
c Yield of 3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6e¢).
d Yield of 3-acetyl-2,5-diphenylfuran (6f¢).
e PPA/Bentonite was used instead of PPA/SiO2.
under reduced pressure below 60 °C, and the resulting reagent was
dried in vacuo (13.3 mbar) at r.t. for 5 h.
Table 4 Reaction of 7 and Various Acids
O
O
O
O
Ph
acid
Silica Gel Supported PPA
Ph
+
PPA (6.0 g) and CHCl3 (150 mL) were placed in the round-bottom
flask, and the mixture was stirred at 50 °C for 1 h. Silica gel
[Wakogel C-200 (Wako Pure Chemical Ind. Ltd), 14.0 g], which
was dried in vacuo at 160 °C for 2 h, was added to the mixture, and
the mixture was stirred for another 1 h. The CHCl3 was removed
with rotary evaporator and the resulting solid was dried in vacuo at
r.t. for 3 h.
toluene
80 °C, 1 h
O
Ph
Ph
Ph
O
O
Ph
7
6f
6f'
Entry
Acid
Yielda (%)
6f
6f¢
31
Furans 4 and 6; General Procedure
1
PPA/SiO2 (30 wt%, 0.5 g)
PPA/Bentonite (10 wt%, 1.0 g)
69
83
60
63
63
A mixture of b-dicarbonyl (3 mmol), a-halo ketone (2 mmol), PPA/
SiO2 (30 wt%, 1.0 g), and Na2CO3/Al2O3 (1.5 mmol, 1.5 g) was
stirred in toluene (10 mL) at 80 °C for 2 h, and then the used sup-
ported reagents were removed by filtration. The filtrate was evapo-
rated to leave crude product, which was purified by column
chromatography.
2
16
36
30
24
3
NaHSO4/SiO2 (2.1 mmol/g, 0.5 g)
ZnCl2/SiO2 (1.5 mmol/g, 1.0 g)
PPA (7.0 g)
4
5b
Ethyl 2-Methyl-5-phenylfuran-3-carboxylate (4a)13
Yellow oil.
IR (neat): 1717, 1234, 1098, 760 cm–1.
a Isolated yield.
b Neat.
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 2.65 (s, 3 H), 4.31
(q, J = 7.1 Hz, 2 H), 6.88 (s, 1 H), 7.24–7.28 (m, 1 H), 7.36–7.40
(m, 2 H), 7.62–7.65 (m, 2 H).
13C NMR (CDCl3): d = 13.9, 14.4, 60.2, 105.5, 115.4, 123.6, 127.6,
128.7, 130.1, 151.7, 158.6, 164.0.
HRMS (TOF-CI): m/z [M + H]+ calcd for C14H15O3: 231.1021;
found: 231.1030.
Melting points were determined on a Yanako Micro melting point
apparatus. Elemental analyses were performed on a Yanako CHN-
corder MT-5. NMR spectra were recorded on a JEOL JNM-GX400
spectrometer or a JEOL JNM-ECX400. Tetramethylsilane (d = 0
ppm) was used as an internal standard for 1H NMR and CDCl3 (d =
77.0 ppm) for 13C NMR. Mass analyses were performed on an Ag-
ilent G1969 LC/MDS TOF spectrometer. IR spectra were recorded
on a Thermo Electron Nicolet 380 spectrometer.
Anal. Calcd for C14H14O3: C, 73.03; H, 6.13. Found: C, 73.03; H,
6.12.
Alumina-Supported Sodium Carbonate
Alumina (ICN Biomedical N-Super 1, 8.41 g) was added to a soln
of Na2CO3 (10 mmol, 1.59 g) in distilled H2O, and the mixture was
stirred at r.t. for 0.5 h. The water was removed by rotary evaporator
Ethyl 5-Phenyl-2-propylfuran-3-carboxylate (4b)
Yellow oil.
IR (neat): 2963, 2933, 1717, 1230, 1107, 1054, 760 cm–1.
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Furans
623
1H NMR (CDCl3): d = 1.00 (t, J = 7.3 Hz, 3 H), 1.37 (t, J = 7.3 Hz,
3 H), 1.73–1.82 (m, 2 H), 3.03 (t, J = 7.3 Hz, 2 H), 4.31 (q, J = 7.3
Hz, 2 H), 6.88 (s, 1 H), 7.25–7.28 (m, 1 H), 7.36–7.40 (m, 2 H),
7.63–7.66 (m, 2 H).
13C NMR (CDCl3): d = 13.8, 14.3, 21.6, 29.7, 60.1, 105.5, 115.1,
123.6, 127.6, 128.7, 130.2, 151.6, 162.5, 164.0.
Allyl 2-Methyl-5-phenylfuran-3-carboxylate (4g)
Yellow oil.
IR (neat): 1717, 1231, 1092, 760 cm–1.
1H NMR (CDCl3): d = 2.65 (s, 3 H), 4.76 (dt, J = 5.50, 1.4 Hz, 2 H),
5.28 (m, 1 H), 5.40 (m, 1 H), 5.97–6.07 (m, 1 H), 6.90 (s, 1 H), 7.24–
7.28 (m, 1 H), 7.36–7.39 (m, 2 H), 7.62–7.65 (m, 2 H).
13C NMR (CDCl3): d = 13.9, 64.8, 105.4, 115.0, 118.1, 123.6, 127.6,
128.7, 129.9, 132.3, 151.7, 158.9, 163.6.
HRMS (TOF-CI): m/z [M + H]+ calcd for C16H19O3: 259.1334;
found: 259.1337.
Anal. Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 74.39; H,
7.08.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H15O3: 243.1015;
found: 243.1024.
Ethyl 2-Heptyl-5-phenylfuran-3-carboxylate (4c)
Yellow oil.
IR (neat): 2928, 2856, 1717, 1229, 1065, 760 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.3 Hz, 3 H), 1.19–1.42 (m, 8 H),
1.37 (t, J = 7.0 Hz, 3 H), 1.74 (quint, J = 7.3 Hz, 2 H), 3.04 (t,
J = 7.3 Hz, 2 H), 4.31 (q, J = 7.3 Hz, 2 H), 6.88 (s, 1 H), 7.24–7.28
(m, 1 H), 7.35–7.39 (m, 2 H), 7.62–7.65 (m, 2 H).
13C NMR (CDCl3): d = 14.0, 14.3, 22.6, 27.7, 28.1, 29.0, 29.2, 31.7,
60.1, 105.4, 114.9, 123.6, 127.5, 128.6, 130.2, 151.5, 162.7, 164.0.
2-Methoxyethyl 2-Methyl-5-phenylfuran-3-carboxylate (4h)
Yellow oil.
IR (neat): 2888, 1717, 1233, 1096 cm–1.
1H NMR (CDCl3): d = 2.66 (s, 3 H), 3.43 (s, 3 H), 3.69–3.71 (m, 2
H), 4.40–4.42 (m, 2 H), 6.91 (s, 1 H), 7.26–7.28 (m, 1 H), 7.38 (t,
J = 7.4 Hz, 2 H), 7.64 (d, J = 7.4 Hz, 2 H).
13C NMR (CDCl3): d = 13.9, 59.0, 63.2, 70.6, 102.5, 105.5, 115.2,
123.6, 127.6, 128.7, 130.0, 151.7, 159.0, 164.0.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O4: 261.1127;
found: 261.1128.
HRMS (TOF-CI): m/z [M + H]+ calcd for C20H27O3: 315.1960;
found: 315.1960.
tert-Butyl 2-Methyl-5-phenylfuran-3-carboxylate (4i)
Yellow oil.
1H NMR (CDCl3): d = 1.58 (s, 9 H), 2.62 (s, 3 H), 6.83 (s, 1 H), 7.26
(t, J = 7.3 Hz, 1 H), 7.37 (t, J = 7.8 Hz, 2 H), 7.63 (d, J = 7.3 Hz, 2
Ethyl 2-Benzyl-5-phenylfuran-3-carboxylate (4d)
White solid; mp 66 °C.
IR (neat): 2980, 2923, 1708, 1259, 1230, 1083, 760 cm–1.
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 4.33 (q, J = 7.1 Hz,
2 H), 4.41 (s, 2 H), 6.91 (s, 1 H), 7.20–7.38 (m, 8 H), 7.61–7.63 (m,
2 H).
13C NMR (CDCl3): d = 14.4, 33.7, 60.4, 105.5, 115.6, 123.8, 126.6,
127.8, 128.5, 128.7, 128.7, 129.9, 137.5, 152.3, 159.6, 163.8.
H).
13C NMR (CDCl3): d = 14.2, 28.6, 106.1, 117.1, 123.9, 127.8, 129.0,
130.5, 151.7, 158.3, 163.8.
Ethyl 5-(4-Chlorophenyl)-2-methylfuran-3-carboxylate (4j)
Yellow solid; mp 79 °C.
IR (neat): 1700, 1248, 1090, 832 cm–1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C20H19O3: 307.1334;
found: 307.1326.
Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.38; H,
6.25.
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 2.64 (s, 3 H), 4.31
(q, J = 7.1 Hz, 2 H), 6.88 (s, 1 H), 7.35 (d, J = 8.3 Hz, 2 H), 7.56 (d,
J = 8.3 Hz, 2 H).
13C NMR (CDCl3): d = 13.9, 14.4, 60.27, 106.0, 115.5, 124.8, 128.6,
128.9, 133.3, 150.6, 158.9, 163.9.
Ethyl 2,5-Diphenylfuran-3-carboxylate (4e)14
White solid; mp 71 °C.
IR (neat): 3130, 2983, 2909, 1703, 1484, 1266, 1230, 1096, 761,
690 cm–1.
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 4.34 (q, J = 7.2 Hz,
2 H), 7.01 (s, 1 H), 7.30–7.74 (m, 1 H), 7.38–7.48 (m, 5 H), 7.74 (d,
J = 7.6 Hz, 2 H), 8.08 (d, J = 7.6 Hz, 2 H).
HRMS (TOF-CI): m/z [M + H]+ calcd for C14H14ClO3: 265.0631;
found: 265.0634.
Anal. Calcd for C14H13ClO3: C, 63.52; H, 4.95. Found: C, 63.43; H,
4.97.
13C NMR (CDCl3): d = 14.3, 60.6, 107.9, 115.8, 123.6, 124.0, 128.1,
128.1, 128.4, 128.8, 129.3, 129.8, 152.3, 156.5, 163.5.
Ethyl 5-(4-Methoxyphenyl)-2-methylfuran-3-carboxylate (4k)15
Yellow solid; mp 58 °C.
HRMS (TOF-CI): m/z [M + H]+ calcd for C19H17O3: 293.1178;
IR (neat): 1697, 1502, 1246, 1026, 831 cm–1.
found: 293.1179.
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 2.63 (s, 3 H), 3.83
(s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.74 (s, 1 H), 6.92 (d, J = 8.8 Hz,
2 H), 7.57 (d, J = 8.8 Hz, 2 H).
Anal. Calcd for C19H16O3: C, 78.06; H, 5.52. Found: C, 78.07; H,
5.49.
13C NMR (CDCl3): d = 13.9, 14.4, 55.3, 60.1, 103.8, 114.2, 115.3,
Benzyl 2-Methyl-5-phenylfuran-3-carboxylate (4f)
Yellow oil.
IR (neat): 1708, 1224, 1086, 757 cm–1.
1H NMR (CDCl3): d = 2.65 (s, 3 H,), 5.30 (s, 2 H), 6.67 (s, 1 H),
7.25–7.28 (m, 1 H), 7.30–7.44 (m, 7 H), 7.63 (d, J = 7.2 Hz, 2 H).
123.1, 125.1, 151.7, 152.3, 159.2, 164.2.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O4: 261.1127;
found: 261.1125.
Anal. Calcd for C15H16O4: C, 69.22; H, 6.20. Found: C, 69.14; H,
6.21.
13C NMR (CDCl3): d = 14.0, 66.0, 105.4, 115.1, 123.7, 127.7, 128.1,
128.2, 128.6, 128.7, 130.0, 136.2, 151.8, 159.0, 163.8.
Ethyl 2-Methyl-5-(4-tolyl)furan-3-carboxylate (4l)
Yellow solid; mp 82 °C.
IR (neat): 1698, 1427, 1229, 1098, 819, 779 cm–1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C19H17O3: 293.1178;
found: 293.1185.
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York

624
T. Aoyama et al.
PAPER
1H NMR (CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H), 2.36 (s, 3 H), 2.64
(s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.82 (s, 1 H), 7.15–7.20 (m, 2 H),
7.53 (d, J = 8.3 Hz, 2 H).
13C NMR (CDCl3): d = 13.9, 14.4, 21.6, 60.2, 104.7, 115.3, 123.6,
127.4, 129.4, 137.5, 151.9, 158.2, 164.1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178;
found: 245.1172.
IR (neat): 2970, 1777, 1717, 1254 cm–1.
1H NMR (CDCl3): d = 1.25 (s, 9 H), 1.34 (t, J = 7.2 Hz, 3 H), 2.54
(s, 3 H), 4.27 (q, J = 7.2 Hz, 2 H), 6.19 (s, 1 H).
13C NMR (CDCl3): d = 4.1, 14.8, 29.2, 32.7, 60.2, 103.0, 113.8,
157.8, 162.5, 164.9.
HRMS (TOF-CI): m/z [M + H]+ calcd for C12H19O3: 211.1334;
found: 211.1328.
Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.70; H,
6.61.
Ethyl 2,4-Dimethyl-5-phenylfuran-3-carboxylate (4s)16
Yellow oil.
Ethyl 2-Methyl-5-(3-tolyl)furan-3-carboxylate (4m)
Yellow oil.
IR (neat): 1711, 1229, 1096, 772 cm–1.
1H NMR (CDCl3): d = 1.39 (t, J = 7.1 Hz, 3 H), 2.38 (s, 3 H), 2.65
(s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 6.86 (s, 1 H), 7.08 (d, J = 7.6 Hz,
1 H), 7.27 (t, J = 7.6 Hz, 1 H), 7.40–7.52 (m, 2 H).
13C NMR (CDCl3): d = 13.9, 14.4, 21.5, 60.2, 105.3, 115.3, 120.8,
124.3, 128.4, 128.6, 130.0, 138.3, 151.8, 158.5, 164.1.
IR (neat): 1715, 1237, 1098 cm–1.
1H NMR (CDCl3): d = 1.38 (t, J = 7.1 Hz, 3 H), 2.46 (s, 3 H), 2.61
(s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 7.27–7.31 (m, 1 H), 7.39–7.43
(m, 2 H), 7.56–7.79 (m, 2 H).
13C NMR (CDCl3): d = 10.9, 14.4, 14.5, 59.9, 115.3, 116.9, 126.1,
127.2, 128.5, 131.0, 147.7, 158.4, 164.8.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178;
found: 245.1176.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178;
found: 245.1173.
3-Acetyl-2-methyl-5-phenylfuran (6a)15
White solid; mp 53 °C.
Ethyl 2-Methyl-5-(2-tolyl)furan-3-carboxylate (4n)
Yellow oil.
IR (neat): 1706, 1225, 1087, 758 cm–1.
1H NMR (CDCl3): d = 1.38 (t, J = 7.1 Hz, 3 H), 2.49 (s, 3 H), 2.65
(s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 6.77 (s, 1 H), 7.19–7.30 (m, 3 H),
7.68 (d, J = 6.8Hz, 1 H).
13C NMR (CDCl3): d = 13.9, 14.4, 21.9, 60.2, 89.2, 109.1, 126.0,
126.7, 127.7, 129.3, 131.1, 134.6, 144.3, 151.1, 158.2.
IR (neat): 3108, 3064, 1672, 1609, 1236, 759, 690 cm–1.
1H NMR (CDCl3): d = 2.45 (s, 3 H), 2.66 (s, 3 H), 6.84 (s, 1 H),
7.26–7.30 (m, 1 H), 7.37–7.41 (m, 2 H), 7.64 (d, J = 8.4 Hz, 2 H).
13C NMR (CDCl3): d = 14.5, 29.1, 105.0, 123.2, 123.6, 128.7, 129.9,
151.2, 157.9, 194.1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C13H13O2: 201.0916;
found: 201.0914.
Anal. Calcd for C13H12O2: C, 77.98; H, 6.04. Found: C, 78.24; H,
6.05.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178;
found: 245.1175.
1-(2-Ethyl-5-phenylfuran-3-yl)propan-1-one (6b)
White solid; mp 36 °C.
IR (neat): 2974, 2933, 1676, 1552, 1200, 920, 758 cm–1.
1H NMR (CDCl3): d = 1.19 (t, J = 7.3 Hz, 3 H), 1.32 (t, J = 7.3 Hz,
3 H), 2.80 (q, J = 7.3 Hz, 2 H), 3.09 (q, J = 7.3 Hz, 2 H), 6.85 (s, 1
H), 7.26–7.30 (m, 1 H), 7.37–7.41 (m, 2 H), 7.64–7.66 (m, 2 H).
13C NMR (CDCl3): d = 7.8, 12.0, 21.8, 34.4, 104.6, 121.7, 123.6,
127.7, 128.7, 130.0, 151.5, 162.7, 197.0.
Ethyl 2-Methyl-5-naphthalen-1-ylfuran-3-carboxylate (4o)
Yellow oil.
IR (neat): 3050, 2980, 2928, 1716, 1239, 1085, 776 cm–1.
1H NMR (CDCl3): d = 1.39 (t, J = 7.1 Hz, 3 H), 2.71 (s, 3 H), 4.35
(q, J = 7.1 Hz, 2 H), 6.98 (s, 1 H), 7.48–7.55 (m, 3 H), 7.71–7.73
(m, 1 H), 7.83–7.89 (m, 2 H), 8.35–8.37 (m, 1 H).
13C NMR (CDCl3): d = 14.0, 14.4, 60.2, 109.8, 115.2, 125.2, 125.2,
126.0, 126.1, 126.7, 127.7, 128.6, 128.8, 130.2, 133.9, 151.0, 158.9,
164.1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O2: 229.1229;
found: 229.1230.
HRMS (TOF-CI): m/z [M + H]+ calcd for C18H17O3: 281.1178;
found: 281.1182
Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 79.07; H,
7.11.
Ethyl 2-Methyl-5-naphthalen-2-ylfuran-3-carboxylate (4p)
White solid; mp 96 °C.
IR (neat): 3114, 2978, 1705, 1439, 1238, 1103 cm–1.
1H NMR (CDCl3): d = 1.39 (t, J = 7.2 Hz, 3 H), 2.70 (s, 3 H), 4.33
(q, J = 7.2 Hz, 2 H), 7.00 (s, 1 H), 7.44–7.51 (m, 2 H), 7.72 (d,
J = 8.5 Hz, 1 H), 7.80–7.87 (m, 3 H), 8.12 (s, 1 H).
2-Benzoyl-2,5-diphenylfuran (6c)
Yellow oil.
IR (neat): 3059, 1682, 1656, 1448, 1279, 769, 690 cm–1.
1H NMR (CDCl3): d = 6.90 (s, 1 H), 7.31–7.51 (m, 9 H), 7.72–7.89
(m, 6 H).
13C NMR (CDCl3): d = 108.6, 122.7, 124.0, 127.3, 128.1, 128.3,
128.3, 128.6, 128.8, 128.9, 129.6, 129.7, 132.8, 137.9, 152.3, 154.9,
191.6.
HRMS (TOF-CI): m/z [M + H]+ calcd for C23H17O2: 325.1229;
found: 325.1233.
13C NMR (400 MHz, CDCl3): d = 14.0, 14.4, 60.3, 106.1, 115.6,
122.0, 122.0, 126.0, 126.6, 127.3, 127.8, 128.1, 128.5, 132.7, 133.4,
151.7, 158.9, 164.1.
HRMS (TOF-CI): m/z [M + H]+ calcd for C18H17O3: 281.1178;
found: 281.1176.
6,6-Dimethyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6d)
Yellow solid; mp 90 °C.
IR (neat): 3100, 2958, 1674, 1437, 1225, 764, 691 cm–1.
Ethyl 5-tert-Butyl-2-methylfuran-3-carboxylate (4q)
Yellow oil.
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Furans
625
1H NMR (CDCl3): d = 1.18 (s, 6 H), 2.41 (s, 2 H), 2.83 (s, 2 H), 6.89
(s, 1 H), 7.26–7.32 (m, 1 H), 7.38–7.44 (m, 2 H), 7.66 (d, J = 7.3
Hz, 2 H).
13C NMR (CDCl3): d = 28.6, 35.3, 37.5, 52.0, 100.7, 121.7, 123.9,
128.0, 128.8, 129.8, 154.5, 165.8, 193.9.
3-Acetyl-2,5-diphenylfuran (6f¢)
Yellow solid; mp 58 °C.
IR (neat): 3059, 1683, 1483, 1229, 770, 702 cm–1.
1H NMR (CDCl3): d = 2.41 (s, 3 H), 6.97 (s, 1 H), 7.28 (t, J = 7.3
Hz, 1 H), 7.36–7.46 (m, 5 H), 7.69 (d, J = 7.3 Hz, 2 H), 7.95–7.97
(m, 2 H).
HRMS (TOF-CI): m/z [M + H]+ calcd for C16H17O2: 241.1229;
found: 241.1230.
13C NMR (CDCl3): d = 29.7, 107.0, 123.8, 124.0, 128.0, 128.2,
Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 80.05; H,
6.70.
128.4, 128.7, 129.5, 129.6, 129.8, 152.4, 155.5, 193.8.
HRMS (TOF-CI): m/z [M + H]+ calcd for C18H15O2: 263.1072;
found: 263.1076.
6,6-Dimethyl-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6d¢)
Anal. Calcd for C18H14O2: C, 82.42; H, 5.38. Found: C, 82.74; H,
5.24.
Yellow solid; mp 103 °C.
IR (neat): 3122, 2948, 2923, 1669, 1471, 756, 690 cm–1.
1H NMR (CDCl3): d = 1.15 (s, 6 H), 2.42 (s, 2 H), 2.80 (s, 2 H),
7.28–7.32 (m, 1 H), 7.35–7.38 (m, 2 H), 7.44 (s, 1 H), 7.64 (d,
J = 8.0 Hz, 2 H).
13C NMR (CDCl3): d = 28.5, 35.0, 37.9, 53.3, 117.7, 125.5, 127.7,
128.3, 128.6, 130.7, 139.7, 167.7, 193.8.
HRMS (TOF-CI): m/z [M + H]+ calcd for C16H17O2: 241.1229;
found: 241.1232.
References
(1) Lipshutz, B. H. Chem. Rev. 1986, 86, 795.
(2) Lansiaux, A.; Dassonneville, L.; Facompré, M.; Kumar, A.;
Stephens, C. E.; Bajic, M.; Tanious, F.; Wilson, W. D.;
Boykin, D. W.; Bailly, C. J. Med. Chem. 2002, 45, 1994.
(3) Nakanishi, K. Natural Products Chemistry; Kodansha Ltd.:
Tokyo, 1974.
(4) Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kwan, P. L.; Lo, T.
H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54,
1995.
(5) Kürt, L.; Czakó, B. Strategic Applications of Named
Reactions in Organic Synthesis; Elsevier Academic:
Amsterdam, 2005.
(6) Stauffer, F.; Neier, R. Org. Lett. 2000, 2, 3535.
(7) Christopfel, W. C.; Miller, L. J. Org. Chem. 1986, 51, 4169.
(8) Bambury, R. E.; Yaktin, H. K.; Wyckoff, K. K.
J. Heterocycl. Chem. 1968, 5, 95.
(9) Chochois, H.; Sauthier, M.; Maerten, E.; Castanet, Y.;
Mortreux, A. Tetrahedron 2006, 62, 11740.
(10) Aoyama, T.; Takido, T.; Kodomari, M. Synlett 2005, 2739.
(11) Aoyama, T.; Orito, M.; Takido, T.; Kodomari, M. Synthesis
2008, 2089.
2-Phenyl-6,7-dihydrobenzofuran-4(5H)-one (6e)13
Yellow solid; mp 136 °C.
IR (neat): 3100, 3053, 2945, 1667, 1436, 764 cm–1.
1H NMR (CDCl3): d = 2.21 (m, J = 6.4 Hz, 2 H), 2.53 (t, J = 6.4 Hz,
2 H), 2.95 (t, J = 6.4 Hz, 2 H), 6.89 (s, 1 H), 7.28–7.31 (m, 1 H),
7.37–7.41 (m, 2 H), 7.64–7.66 (m, 2 H).
13C NMR (CDCl3): d = 22.5, 23.4, 37.6, 100.8, 122.9, 123.9, 128.0,
128.7, 129.7, 154.2, 166.7, 194.5.
HRMS (TOF-CI): m/z [M + H]+ calcd for C14H13O2: 213.0916;
found: 213.0918.
3-Benzoyl-2-methyl-5-phenylfuran (6f)17
Yellow oil.
IR (neat): 3059, 2919, 1652, 1262, 901, 762 cm–1.
(12) Aoyama, T.; Okada, K.; Nakajima, H.; Matsumoto, T.;
Takido, T.; Kodomari, M. Synlett 2007, 387.
(13) Alagoz, O.; Yilmaz, M.; Tarik, P. A. Synth. Commun. 2006,
36, 1005.
(14) Lutz, R.; McGinn, C. E.; Bailey, P. S. J. Am. Chem. Soc.
1943, 65, 843.
(15) Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44,
3343.
(16) Wang, G.; Guan, Z.; Tang, R.; He, Y. Synth. Commun. 2010,
40, 370.
1H NMR (CDCl3): d = 2.60 (s, 3 H), 6.81 (s, 1 H), 7.27 (t, J = 7.3
Hz, 1 H), 7.36–7.40 (m, 2 H), 7.47–7.50 (m, 2 H), 7.56–7.59 (m, 1
H), 7.64–7.67 (m, 2 H), 7.83–7.85 (m, 2 H).
13C NMR (CDCl3): d = 14.3, 106.5, 122.3, 123.7, 127.7, 128.4,
128.7, 128.9, 129.9, 132.2, 139.0, 151.5, 158.9, 191.2.
HRMS (TOF-CI): m/z [M + H]+ calcd for C18H15O2: 263.1072;
found: 263.1075.
Anal. Calcd for C18H14O2: C, 82.42; H, 5.38. Found: C, 82.28; H,
5.40.
(17) Babudri, F.; Cicco, S. R.; Farinola, G. M.; Lopez, L. C.;
Naso, F.; Pinto, V. Chem. Commun. 2007, 3756.
Synthesis 2011, No. 4, 619–625 © Thieme Stuttgart · New York