DMAP-catalyzed cascade reaction: One-pot synthesis of benzofurans in water

Article abstract of DOI:10.1016/j.tet.2010.09.095

A series of benzofurans were efficiently synthesized in good to excellent yields using 4-dimethylaminopyridine (DMAP) catalyzed cascade reaction between salicylaldehydes and halogenated ketones in water at 80 °C opened atmosphere.

Full text of DOI:10.1016/j.tet.2010.09.095

Tetrahedron 66 (2010) 9629e9633
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
DMAP-catalyzed cascade reaction: one-pot synthesis of benzofurans in water
*
Yongjia Shang , Cuie Wang, Xinwei He, Kai Ju, Min Zhang, Shuyan Yu, Jiaping Wu
Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Key Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science,
Anhui Normal University, Wuhu 241000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 June 2010
Received in revised form 3 August 2010
Accepted 29 September 2010
Available online 4 November 2010
A series of benzofurans were efficiently synthesized in good to excellent yields using 4-dimethylami-
nopyridine (DMAP) catalyzed cascade reaction between salicylaldehydes and halogenated ketones in
water at 80 ꢀC opened atmosphere.
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Keywords:
Benzofuran
Cascade reaction
Dimethylaminopyridine
Halogenated ketones
Salicylaldehydes
1. Introduction
In the context of our studies aimed for the development of efficient
catalytic organic synthsis,23 we have focused on the utility of DMAP.
Benzofuran derivatives are important components of those clin-
ically used plant extracts due to their excellent properties, such as
antibacterial,1 antimicrobial,2 antitumor,3 and the ability to control
calcium level.4 Many research efforts have been focused on the ef-
ficient synthesis of these molecules.5 Typical approaches including:
(1) intramolecular enolated O-arylation6 and thio-enolated S-aryla-
tion,7 (2) annulation of a furan ring onto a preexisting benzene ring,8
and (3) catalyzed cyclization-coupling.9,10 However, the first two
approaches generally require multi-step synthesis, while the third
one often requires the usage of transition-metals,11,12 and only lim-
ited types of benzofuran derivatives are accessible using these syn-
thetic approaches. The RapeStoermer reaction provides opportunity
for the direct preparation of benzofurans via base-mediated reaction
of salicylaldehydes with haloketones. Recently reported solid state
studies on the RapeStoermer reaction provided valuable insights
into the mechanistic details of this reaction.13
Herein we report a facile synthesis of a series of benzofurans using
DMAP-catalyzed cascade reaction between readily available sali-
cylaldehydes 1 and halogenated ketones 2 in water (Scheme 1).
R2
O
O
R3
O
R2
R1
i
+
X
R1
R3
O
OH
1
3
2
Scheme 1. Synthesis of benzofuran derivatives conditions: (1) DMAP (0.1 equiv), (2)
Na2CO3 (1.5 equiv), (3) H2O (solvent), 80 ꢀC, 5 h.
2. Results and discussion
Initially, DABCO (1, 4-diazabibicyclo [2.2.2] octane) was used as
DMAP and its analogs have been widely used in many organic
synthesis as catalyst, used, for example, in the acylation reactions,14
aldol reactions,15 and BayliseHillman reactions.16 Recently, these
catalysts have also been used in the Michael-addition17 and ester-
ification18 reactions in water. Attracted to the efficiency of these
organo-catalysts and the advantages of using water as solvent.19e22
catalyst in the cascade reaction between salicylaldehyde 1 and
a-bromoacetophenone 2 in the presence of Na2CO3 in water as
shown in Table 1 (entry 1). To our delight, the desired benzofuran
3a24,25 was obtained in 80% yield after reacting at 80 ꢀC for 5 h. It
was characterized by 1H, 13C NMR and X-ray (Fig. 1). For the opti-
mization of the reaction condition, various catalysts, different sol-
vents, varying temperature, and reaction time were investigated
and the results are summarized in Tables 1 and 2.
Among the various catalysts studied (Table 1), 3-HQD
(3-hydroxyquinuclidine) (entry 2) and DMAP (4-dimethylamino-
pyridine) (entry 7) showed higher catalytic activities, and gave
* Corresponding author. Fax: þ86 553 3869303; e-mail address: shyj@mail.ahnu.
edu.cn (Y. Shang).
0040-4020/$ e see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.095

9630
Y. Shang et al. / Tetrahedron 66 (2010) 9629e9633
Table 1
compound 3 in 82% and 88% yields, respectively. We thus chose
DMAP as catalyst, and further optimized the reaction condition as
summarized in Table 2.
Optimization of catalystsa
Catalyst
Na2CO3
O
CHO
+
OH
Br
This reaction was carried out in a variety of solvents, such as THF,
DMF, toluene, and water. In this study, benzofuran 3 was obtained
in 80% and 85% yield with DMF, THF as solvent at reflux for 5 h
(entries 2 and 3), but it obtained in 88% yield with water as solvent
at 80 ꢀC at the same time (entry 7). Thus, water turns out to be the
best solvent for this reaction. And then we optimized the reaction
with water as solvent (entries 6e11). At room temperature, com-
pound 3 was obtained in low yield in water (entry 11). When the
temperature increased to 80 ꢀC, the yield increased to 88%, and
the reaction time reduced to 5 h (entry 7). Further increasing the
temperature to 100 ꢀC, a comparable result was obtained (entry 6).
Thus, we eventually settle down the optimized reaction condition
to be the combination of 10 mol % of DMAP as catalyst, water as
solvent and Na2CO3 as base.
Utilizing the optimized reaction condition, various salicylalde-
hydes 1 and halogenated ketones 2 were used to test the versatility
of this reaction, and the results were summarized in Table 3. Many
functionalities were able to survive from this reaction. Among var-
ious salicylaldehydes 1 investigated (entries 1,11, and 17), molecules
with electron-withdrawing groups (Br and Cl) attached generally
provides higher yields. Among various halogenated aromatic ke-
tones 2 investigated, molecules with electron-donating group at-
tached on the benzene rings of R3 often gave higher yields, while
those with electron-withdrawing groups attached, such as 3d led to
H2O,80oC,5h
O
O
1
3
2
Entry
1
Catalyst
Yield (%)
80
2
82
3
4
5
30
30
42
6
7
51b
88
18
8
d
a
lower yields. Compared with
chloroacetophenone gave lower yield (82%, entry 10).
a-bromoacetophenone (entry 1),
Reaction conditions: salicylaldehydes(1.0 mmol), a-bromoacetophenone (1.0 mmol),
catalyst (0.1 mmol), water (5 mL), Na2CO3 (1.5 mmol), 80 ꢀC, 5 h.
b
This catalyst was synthesized in our laboratory.
Table 3
DMAP-catalyzed cascade reaction for the formation of benzofuransa
O
R2
O
DMAP
R2
R3
O
R1
Na2CO3(1.5 equiv)
H2O, 80oC, 5h
+
X
R1
R3
OH
O
1
2
3
Entry
R1
R2
R3
X
Yield (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
C6H5
Br
Br
Br
Br
Br
Br
Cl
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
88
81
90
60
71
75
60
80
80
95
83
73
70
71
68
90
87
91
82
72
65
72
70
70
CH3C6H4
CH3OC6H4
BrC6H4
p-NO2C6H4
m-NO2C6H4
OCH2CH3
ClCH2
Fig. 1. X-ray crystal structure of 3a.
Cl
Cl
Table 2
9
CH3
C6H5
Optimization of reaction conditionsa
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
CH3C6H4
CH3OC6H4
BrC6H4
p-NO2C6H4
m-NO2C6H4
C6H5
CH3C6H4
CH3OC6H4
BrC6H4
p-NO2C6H4
m-NO2C6H4
C6H5
DMAP
Na2CO3
O
CHO
OH
Br
+
O
O
1
3
2
H
H
H
H
Entry
Solvent
Temp (ꢀC)
Time(h)
Yield (%)
3s
3t
3u
3v
3w
3x
1
2
3
4
5
6
7
8
Toluene
THF
DMF
CH2Cl2
CH3CN
H2O
H2O
H2O
H2O
H2O
Reflux
Reflux
Reflux
Reflux
Reflux
100
80
80
60
40
5
5
5
8
4
5
5
5
8
83
85
80
20
87
87
88
87b
40
36
20
H
CH3
CH3
CH3
H
H
BrC6H4
p-NO2C6H4
a
Reaction conditions: salicylaldehydes (1.0 mmol),
a-bromoacetophenone
(1.0 mmol), water (5 mL), DMAP (0.1 mmol), and Na2CO3 (1.5 mmol), 80 ꢀC, 5 h.
9
10
11
10
12
Interestingly, the usage of 1,3-dichlorin acetone as the starting
material led to the formation of 3h (Scheme 2), containing two
benzofuran rings, in 80% yield using the optimized reaction con-
dition (entry 8).
H2O
rt
a
Reaction conditions: salicylaldehydes (1.0 mmol),
a-bromoacetophenone
(1.0 mmol), solvent (5 mL), catalyst (0.1 mmol), and Na2CO3 (1.5 mmol).
b
Catalyst (0.2 mmol).

Y. Shang et al. / Tetrahedron 66 (2010) 9629e9633
9631
O
300 MHz. All NMR samples were run in CDCl3 and chemical shifts
are expressed as parts per million relative to internal Me4Si and the
metallic nature of the particles was confirmed with a UV spectro-
photometer (Shimadzo). Column chromatography was carried out
with the use of silica gel (200e300 mesh), purchased from Qingdao
Haiyang Chemical Plang, China.
O
DMAP
H
Na2CO3(1.5 equiv)
O
+
O
Cl
Cl
H2O, 80oC, 5h
OH
O
1
2
3h
Scheme 2. DMAP-catalyzed one-pot synthesis of the dibenzofuran-2-ylmethanone
(3h).
The mechanism for this reaction is complicated, however it is
reasonable to propose the following explanation as shown in
Scheme 3 for this reaction based on our experimental results and
literature reports.25 We reasoned that DMAP may has an increased
efficiency for this reaction for two reasons. The DMAP could lead to
more efficient ammonium salt to enhance its solubility in water.
The hydrogen activity of the ammonium salt would be more higher
and it would be taken away by sodium carbonate in water to
generate a carbanion to enhance its nucleophilic properties. The
nitrogen of the catalyst I displaces the halogen of compound 2 to
generate the corresponding ammonium salt II. The enolate form of
the ammoniumylide III nucleophilic attack at the carbonyl group of
salicylaldehyde 1 to generate intermediate IV, which was further
converted to the intermediate V via proton-transfer process. The
key precursor-compound 4 was generated from the intramolecular
nucleophilic addition within intermediate V, and was further con-
verted to the desired target compound 3 through dehydration
process. Meanwhile, catalyst I was regenerated.
4.2. General procedure for the synthesis of benzofurans
To DMAP (10% mmol) and Na2CO3 (1.5 mmol) in water, haloge-
nated ketone (1 mmol) and salicylaldehyde (1 mmol) were added.
The resulting mixture was stirred at 80 ꢀC for 5 h. The mixture was
extracted with CH2Cl2 (30 mL), washed with water. The organic
layers were combined, dried over anhydrous Na2SO4, and evapo-
rated in vacuum. The residue was purified by column chromatog-
raphy on silica gel (200e300 mesh) (EtOAc/petroleum¼1/20, v/v)
to give the pure product 3.
4.2.1. Compound 3a24
1H, C6H4), 8.03 (d, J¼8.0 Hz, 1H, C6H4), 7.67e7.75 (m, J¼8.0 Hz, 2H,
C6H4), 7.62e7.66 (m, 2H, C6H4CO), 7.57 (s, 1H, C4HO), 7.51e7.54 (m,
2H, C6H4CO), 7.37e7.49 (s, 1H, C6H4CO) ppm; 13C NMR (CDCl3,
.
1H NMR (CDCl3, 300 MHz)
d
8.06 (d, J¼7.6 Hz,
75 MHz)
d 184.4, 155.9, 152.1, 137.1, 132.9, 129.6, 129.4, 128.5, 128.4,
126.7, 123.9, 123.3, 116.6, 112.5 ppm.
4.2.2. Compound 3b24 1H NMR (CDCl3, 300 MHz)
d 7.98 (d,
.
O
O
J¼7.8 Hz, 1H, C6H4), 7.74 (d, J¼8.1 Hz, 1H, C6H4), 7.71e7.74 (m,
J¼8.0 Hz, 2H, C6H4), 7.63e7.66 (m, 2H, CH3C6H4CO), 7.50 (s, 1H,
C4HO), 7.31e7.47 (m, 2H, CH3C6H4CO), 2.47 (s, 3H, CH3C6H4CO)
R
R
OH
N
- H2O
O
O
X
O
ppm; 13C NMR (CDCl3, 75 MHz)
d
183.7, 154.3, 153.3, 144.1, 129.7,
R
N
4
3
2
I
129.5, 129.3, 128.5, 128.3, 122.5, 115.0, 113.6, 21.8 ppm.
N
N
O
X
O
N
4.2.3. Compound 3c24 1H NMR(CDCl3, 300 MHz)
.
d
8.09(d, J¼9.0 Hz,
N
R
R
2H, CH3OC6H4CO), 7.71 (d, J¼8.1 Hz, 1H, C6H4), 7.62 (d, J¼8.7 Hz, 1H,
C6H4), 7.50 (s, 1H, C4HO), 7.44e7.49 (m, 1H, C6H4), 7.30e7.33 (m, 1H,
C6H4), 6.97e7.02 (m, 2H, CH3OC6H4CO), 3.89 (s, 3H, CH3OC6H4CO)
182.9, 163.6, 155.5, 152.7, 134.7,
131.9, 128.3, 127.1, 123.9, 123.2, 115.6, 113.9, 112.5, 55.6 ppm.
O
II
Na2CO3
V
HO
N
ppm; 13C NMR (CDCl3, 75 MHz)
d
O
NaX +
NaHCO3
N
R
OH
N
O
4.2.4. Compound 3d24
.
1H NMR (CDCl3, 300 MHz)
d
7.96 (d, J¼8.4
O
IV
N
R
Hz, 1H, C6H4), 7.93 (d, J¼8.1 Hz, 2H, BrC6H4CO),7.73e7.76 (m, 1H,
C6H4), 7.70e7.72 (m, 2H, BrC6H4CO), 7.68 (s, 1H, C4HO), 7.49e7.56
(m, 1H, C6H4), 7.32e7.37 (m, 1H, C6H4) ppm; 13C NMR (CDCl3,
75 MHz) d 182.9, 154.3, 153.0, 136.5, 131.9, 131.6, 129.8, 128.9, 128.4,
128.1, 122.7, 115.4, 113.7 ppm.
III
O
H
1
HO
Scheme 3. Possible mechanism for the synthesis of benzofurans.
4.2.5. Compound 3e. Unknown, 1H NMR (CDCl3, 300 MHz)
(d, J¼6.90 Hz, 2H, NO2C6H4CO), 8.25 (d, J¼6.91 Hz, 2H, NO2C6H4CO),
7.83 (d, J¼8.1 Hz, 1H, C6H4), 7.63e7.71 (m, 2H, C6H4), 7.60 (s, 1H,
C4HO), 7.33e7.59 (m, 1H, C6H4) ppm; 13C NMR (CDCl3, 75 MHz)
d 8.42
3. Conclusions
In conclusion, we have developed an efficient DMAP-catalyzed
RapeStoermer reaction for the efficient generation of a series of
2-aryl-benzofurans in excellent yields. This reaction contains cer-
tain value from a green-chemistry viewpoint, as well as in terms of
practicality. This reaction features with mild reaction condition and
wide access of the starting materials. This mild annulation strategy
developed here may find application in the synthesis of other
hetero-containing aromatic compounds.
d
181.2, 154.7, 152.4, 148.2, 137.8, 135.3, 135.1, 133.9, 131.6, 129.9,
128.5, 127.6, 127.4, 126.1, 125.9, 124.9, 124.8, 124.5, 117.4, 115.8, 115.7,
114.1, 111.6 ppm; IR (KBr): 3753, 3666, 3201, 2958, 2922, 2850,
n
2349, 2308, 1651, 1598, 1556, 1519, 1469, 1454, 1336, 1301, 1263,
1190, 1128, 1101, 972, 866, 850, 758 cmꢁ1; HRMS (ESI) calcd for
C15H9NO4 ([MþH]þ) 267.0532, found 267.1674.
4.2.6. Compound 3f. Unknown, 1H NMR (CDCl3, 300 MHz)
d 8.42 (d,
4. Experimental section
4.1. General methods
J¼8.7 Hz, 1H, NO2C6H4CO), 8.38 (d, J¼8.3, 1H, NO2C6H4CO), 8.24 (d,
J¼8.4 Hz, 1H, NO2C6H4CO), 8.20e8.24 (m, 1H, NO2C6H4CO), 7.85 (d,
J¼7.8 Hz, 1H, C6H4), 7.67e7.82 (m, 1H, C6H4), 7.64 (s, 1H, C4HO),
7.53e7.62 (m, 1H, C6H4), 7.35e7.40 (m, 1H, C6H4) ppm; 13C NMR
All reagents involved in the experiments were commercially
available and used without further purification. 1H NMR and 13C
NMR spectra (300 MHz) were recorded on a Bruker spectrospin
(CDCl3, 75 MHz)
123.3, 116.1, 115.9, 114.1 ppm; IR (KBr):
2852, 2349, 2308, 1651, 1606, 1548, 1525, 1475, 1355, 1332, 1300,
d
181.8, 154.7, 141.5, 132.1, 130.5, 128.5, 123.7, 117.4,
n
3672, 3278, 2958, 2924,

9632
Y. Shang et al. / Tetrahedron 66 (2010) 9629e9633
1261, 1190, 1134, 1085, 997, 921, 848, 756, 725 cmꢁ1; HRMS (ESI)
NO2C6H4CO), 7.84 (s, 1H, C4HO), 7.61e7.66 (m, 1H, BrC6H3),
7.50e7.56 (m, 1H, BrC6H3) ppm; 13C NMR (CDCl3, 75 MHz)
181.6,
155.0, 152.7, 148.5, 138.1, 135.6, 135.4, 134.2, 132.3, 128.8, 127.9,
127.7, 126.3, 125.3, 125.2, 124.8, 117.8, 116.2, 116.1, 114.5 ppm; IR
calcd for C15H9NO4 ([MþH]þ) 268.0565, found 268.0599.
d
4.2.7. Compound 3g26
.
1H NMR (CDCl3, 300 MHz)
d
7.67 (d, J¼7.5 Hz,
1H, C6H4), 7.59 (d, J¼7.8 Hz, 1H, C6H4), 7.52 (s, 1H, C4HO), 7.41e7.46
(KBr): n 3743, 3672, 3105, 2924, 2854, 2349, 2308, 1651, 1597, 1523,
(m, 1H, C6H4), 7.27e7.32 (m, 1H, C6H4), 4.45 (t, J¼6.9, 2H, CH2CH3),
1442, 1404, 1342, 1309, 1269, 1213, 1186, 1136, 1105, 1058, 985, 900,
850, 815, 777 cmꢁ1; HRMS (ESI) calcd for C15H8BrNO4 ([MþH]þ)
346.9616, found 346.4251.
1.43 (q, J¼6.6, 3H, CH2CH3) ppm; 13C NMR (CDCl3, 75 MHz)
d 159.6,
155.7, 145.7, 127.6, 126.9, 123.8, 122.8, 113.8, 112.4, 61.5, 14.3 ppm.
4.2.8. Compound 3h. Unknown, 1H NMR (CDCl3, 300 MHz)
d
8.01
4.2.16. Compound 3p24 1H NMR (CDCl3, 300 MHz)
. d 8.03 (d,
(s, 2H, C4HO), 7.76e7.90 (m, 2H, C6H4), 7.64e7.67 (m, 2H, C6H4),
J¼6.8 Hz, 2H, C6H5CO), 7.69 (s, 1H, ClC6H3), 7.68 (s, 1H, C4HO),
7.49e7.54 (m, 2H C6H4), 7.32e7.37 (m, 2H, C6H4) ppm; 13C NMR
7.62e7.65 (m, 2H, C6H5CO), 7.54e7.56 (m,1H, C6H5CO), 7.41e7.52 (m,
(CDCl3, 75 MHz)
d
171.6, 155.9, 151.6, 128.7, 127.1, 124.1, 123.5, 116.2,
3745, 3666, 3304, 2924, 2349, 2308, 1768,
2H, ClC6H3) ppm; 13C NMR (CDCl3, 75 MHz)
d
184.3, 154.2, 153.1,
112.5 ppm; IR (KBr):
n
136.8, 133.2, 129.6, 129.5, 128.6, 128.2, 122.6, 115.5, 113.6 ppm.
1714, 1651, 1631, 1612, 1543, 1473, 1359, 1332, 1303, 1257, 1155, 1134,
987, 939, 889, 866, 748 cmꢁ1; HRMS (ESI) calcd for C17H10O3
([MþH]þ) 263.0663, found 263.0692.
4.2.17. Compound 3q24 1H NMR(CDCl3, 300 Hz)
.
d
7.94 (d, J¼8.0 Hz,
2H, CH3C6H4CO), 7.67 (s, 1H, C4HO), 7.55 (s, 1H, ClC6H3), 7.39e7.43
(m, 2H, ClC6H3), 7.31e7.34 (m, 2H, CH3C6H4CO), 2.45 (s, 3H,
4.2.9. Compound 3i27
.
1H NMR (CDCl3, 300 MHz)
d
8.20 (d, J¼7.8 Hz,
C6H4CH3) ppm; 13C NMR (CDCl3, 75 MHz)
d
183.5,154.3,153.5,144.2,
1H, C6H4), 7.63 (s, 1H, C4HO), 7.43e7.47 (m, 1H, C6H4), 7.25e7.37 (m,
134.2, 129.7, 129.5, 129.3, 128.5, 128.3, 122.6, 115.0, 113.6, 21.7 ppm.
2H, C6H4), 2.49 (s, 3H, COCH3) ppm; 13C NMR (CDCl3, 75 MHz)
d
181.7, 153.6, 146.7, 142.5, 130.8, 130.5, 130.3, 128.1, 127.5, 126.8,
4.2.18. Compound 3r24 1H NMR (CDCl3, 300 MHz)
d 8.09 (d,
.
1376.7, 123.4, 123.0, 122.4, 120.5, 117.1, 115.9, 115.7, 111.2, 9.1 ppm.
J¼8.16 Hz, 2H, CH3OC6H4CO), 7.67 (s, 1H, C4HO), 7.56 (s, 1H, ClC6H3),
7.40e7.44 (m, 2H, ClC6H3), 6.99e7.02 (m, 2H, CH3OC6H4CO), 3.90 (s,
4.2.10. Compound 3j24 1H NMR (CDCl3, 300 MHz)
.
d
8.07 (s, 1H,
3H, CH3OC6H4CO) ppm; 13C NMR (CDCl3, 75 MHz)
d
182.4, 163.8,
BrC6H3), 7.88 (d, J¼7.8 Hz, 2H, C6H5CO), 7.68 (d, J¼7.7 Hz, 2H,
154.0, 132.0, 129.4, 128.3, 122.5, 114.5, 114.0, 113.6, 55.6 ppm.
C6H5CO), 7.64e7.66 (m, 1H, C6H5CO), 7.58 (s, 1H, C4HO), 7.47e7.55
(m, 2H, BrC6H3) ppm; 13C NMR (CDCl3, 75 MHz)
d
184.0, 154.6,
4.2.19. Compound 3s24 1H NMR (CDCl3, 300 MHz)
d 7.91e7.96 (m,
.
153.3, 136.6, 133.2, 131.3, 129.5, 128.9, 128.6, 125.7, 123.4, 117.0,
115.3, 114.0 ppm.
2H, BrC6H4CO), 7.70 (s, 1H, C4HO), 7.68 (s, 1H, ClC6H3), 7.48e7.58 (m,
2H, BrC6H4CO), 7.44e7.48 (m, 2H, ClC6H3) ppm; 13C NMR (CDCl3,
75 MHz)
d 182.1, 154.5, 152.7, 150.3, 141.6, 130.5, 130.1, 129.5, 127.9,
4.2.11. Compound 3k24
.
1H NMR(CDCl3, 300 MHz)
d
7.98 (s, 1H,
123.8, 123.6, 122.9, 116.3, 113.7 ppm.
BrC6H3), 7.96 (d, J¼8.0 Hz, 2H, CH3C6H4CO), 7.86 (d, J¼8.1 Hz, 1H,
CH3C6H4CO), 7.62e7.65 (m, 1H, CH3C6H4CO), 7.53e7.57 (m, 1H,
BrC6H3), 7.45 (s, 1H, C4HO), 7.33e7.36 (m, 1H, BrC6H3), 2.47 (s, 3H,
4.2.20. Compound 3t. Unknown, 1H NMR (CDCl3, 300 MHz)
d 8.40
(d, J¼7.8 Hz, 2H, NO2C6H4CO), 8.22 (d, J¼7.8 Hz, 2H, NO2C6H4CO), 7.74
(s,1H, C4HO), 7.60 (s,1H, ClC6H3), 7.48e7.57 (m, 2H, ClC6H3) ppm; 13
NMR (CDCl3, 75 MHz) 182.2, 154.2, 152.8, 150.6, 141.6, 130.5, 130.3,
129.5, 127.9, 123.8, 123.6, 122.8, 116.3, 113.8 ppm; IR (KBr): 3670,
CH3C6H4CO) ppm; 13C NMR (CDCl3, 75 MHz)
d
183.5, 154.2, 153.3,
C
144.1, 134.1, 131.1, 129.6, 129.3, 128.9, 125.6, 116.9, 114.8, 114.0,
21.7 ppm.
d
n
3136, 3103, 2920, 2850, 2349, 2308, 1732, 1645, 1598, 1523, 1454,
1340, 1309, 1263, 1184, 1134, 1103, 974, 850, 812, 775 cmꢁ1; HRMS
(ESI) calcd for C15H8ClNO4 ([MþH]þ) 301.0142, found 301.1378.
4.2.12. Compound 3l24 1H NMR (CDCl3, 300 MHz)
. d 8.08 (s, 1H,
BrC6H3), 8.06 (d, J¼8.5 Hz, 2H, CH3OC6H4CO), 7.66 (d, J¼7.7 Hz, 1H,
BrC6H3), 7.51 (s, 1H, C4HO), 7.41e7.43 (m, 1H, BrC6H3), 6.96e7.01 (m,
2H, CH3OC6H4CO), 3.89 (s, 3H, CH3OC6H4CO) ppm; 13C NMR (CDCl3,
4.2.21. Compound 3u. Unknown, 1H NMR (CDCl3, 300 MHz)
d 8.41
75 MHz)
114.4, 113.9, 113.5, 55.6 ppm.
d
182.4, 163.8, 154.0, 134.9, 132.0, 129.5, 129.4, 128.2, 122.5,
(s, 1H, NO2C6H4CO), 8.38 (d, J¼8.7 Hz, 2H, NO2C6H4CO), 8.22 (d,
J¼8.7 Hz, 1H, NO2C6H4CO), 7.68e7.74 (m, 1H, ClC6H3), 7.57 (s, 1H,
C4HO), 7.56 (s,1H, ClC6H3), 7.50e7.52 (m,1H, ClC6H3) ppm; 13C NMR
4.2.13. Compound 3m24 1H NMR(CDCl3, 300 Hz)
.
d
7.96 (s, 1H,
(CDCl3, 75 MHz)
127.9, 127.4124.5, 122.8, 116.0, 113.7 ppm; IR (KBr):
d
181.5, 154.4, 152.8, 148.2,137.8, 135.1,129.9, 129.4,
3672, 3134,
BrC6H3), 7.93 (d, J¼8.5 Hz, 2H, BrC6H4CO), 7.70 (d, J¼8.1 Hz, 2H,
n
BrC6H4CO), 7.67e7.69 (m, 1H, BrC6H3), 7.58 (s, 1H, C4HO), 7.45e7.49
3089, 2956, 2924, 2850, 2349, 2320, 1651, 1612, 1537, 1521, 1471,
1440, 1361, 1317, 1215, 1190, 1138, 1093, 1062, 987, 912, 879, 710,
715 cmꢁ1; HRMS (ESI) calcd for C15H8ClNO4 ([MþH]þ) 301.0142,
found 301.1412.
(m, 1H, BrC6H3) ppm; 13C NMR (CDCl3, 75 MHz)
d 183.2, 154.3, 153.0,
135.6, 135.5, 131.9, 131.0, 129.8, 128.9, 128.4, 128.1, 122.7, 115.4,
113.8 ppm.
4.2.14. Compound 3n. Unknown, 1H NMR (CDCl3, 300 MHz)
d
8.41
4.2.22. Compound 3v. Unknown, 1H NMR (CDCl3, 300 MHz)
d 8.07e
(d, J¼8.3 Hz, 2H, NO2C6H4CO), 8.20e8.25 (m, 2H, NO2C6H4CO), 7.91
8.12 (m, 2H, C6H5CO), 7.59e7.62 (m, 2H, C6H5CO), 7.54e7.55 (m, 1H,
C6H5CO), 7.52e7.53 (m, 1H, C6H4), 7.49e7.52 (m, 2H, C6H4),
7.34e7.39 (m, 1H, C6H4), 2.65 (s, 3H, CH3C4O) ppm; 13C NMR
(s, 1H, BrC6H3), 7.66 (s, 1H, C4HO), 7.63e7.65 (m, 1H, BrC6H3),
7.52e7.56 (m, 1H, BrC6H3) ppm; 13C NMR (CDCl3, 75 MHz)
d
181.4,
154.3,152.8,148.2,137.8,135.1,130.1,129.9,129.4,127.9,127.4,124.4,
122.8, 116.0, 113.7 ppm; IR (KBr): 3745, 3670, 3280, 3103, 2924,
(CDCl3, 75 MHz)
128.3, 128.2, 127.6, 127.5, 126.9, 123.3, 121.5, 112.3, 10.1 ppm; IR
(KBr): 3665, 3198, 2958, 2850, 2349, 2308, 1748, 1672, 1587, 1545,
d 185.9, 154.3, 148.3, 137.9, 132.6, 129.8, 129.2,
n
1852, 2349, 2308, 1699, 1651, 1598, 1523, 1436, 1340, 1309, 1267,
1186, 1134, 1105, 1045, 975, 898, 850, 812, 775 cmꢁ1; HRMS (ESI)
calcd for C15H8BrNO4 ([MþH]þ) 346.9616, found 346.3323.
n
1512, 1457, 1412, 1296, 1258, 1090, 1025, 987, 875, 835, 756,
721 cmꢁ1; HRMS (ESI) calcd for C16H12O2 ([MþH]þ) 237.0871,
found 237.0818.
4.2.15. Compound 3o. Unknown, 1H NMR (CDCl3, 300 MHz)
d 8.41
(s, 1H, NO2C6H4CO), 8.36 (d, J¼8.7 Hz, 1H, NO2C6H4CO), 8.23 (d,
4.2.23. Compound 3w. Unknown, 1H NMR (CDCl3, 300 MHz)
(d, J¼8.1, 2H, NO2C6H4CO), 8.25 (d, J¼8.1, 2H, NO2C6H4CO),
d 8.37
J¼8.1 Hz, 1H, NO2C6H4CO), 7.91 (s, 1H, BrC6H3), 7.85e7.91 (m, 1H,

Y. Shang et al. / Tetrahedron 66 (2010) 9629e9633
9633
Fang, Y.; Prakash, I. J. Org. Chem. 2001, 66, 5613e5615; (e) Hou, X.-L.; Yang, Z.;
Wong, H. N. C. Furans and Benzofurans In. Progress in Heterocyclic Chemistry;
Gribble, G. W., Gilchrist, T. L., Eds.; Pergamon: Oxford, England, 2002; Vol. 14,
pp 139e179.
7.73e7.76 (m, 2H, C6H4), 7.36e7.54 (m, 2H, C6H4), 2.71 (s, 3H,
CH3C4O) ppm; 13C NMR (CDCl3, 75 MHz)
183.7, 154.5, 149.8, 142.8,
130.7, 130.2, 129.8, 129.0, 123.7, 123.5, 122.9, 122.6, 121.8, 121.5,
112.3, 10.2 ppm; IR (KBr): 3645, 3278, 2958, 2924, 2852, 2349,
2308, 1732, 1651, 1602, 1548, 1521, 1454, 1394, 1302, 1261, 1121,
1054, 987, 898, 848, 756 cmꢁ1; HRMS (ESI) calcd for C16H11NO4
([MþH]þ) 281.0688, found 281.0493.
d
6. Eidamshaus, C.; Burch, D. J. Org. Lett. 2008, 4211e4214.
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8. (a) Thielges, S.; Meddah, E.; Bisseret, P.; Eustache, J. Tetrahedron Lett. 2004, 45,
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ꢀ
Alonso, F.; Sanchez, D.; Soler, T.; Yus, M. Adv. Synth. Catal. 2008, 350,
4.2.24. Compound 3x. Unknown, 1H NMR (CDCl3, 300 MHz)
d 7.97
2118e2126.
ꢀ
ꢀ
(d, J¼8.6, 2H, BrC6H4CO), 7.68e7.71 (m, 2H, BrC6H4CO), 7.64e7.67
10. (a) Jose, B.; Henar, V.-V.; Alfredo, B.; Jose, M. G. Adv. Synth. Catal. 2005, 347,
526e530; (b) Xiao, Y.-J.; Zhang, J.-L. Adv. Synth. Catal. 2009, 351, 617e629.
11. Zhang, H.; Feneira, E. M.; Stoltz, B. M. Angew. Chem., Int. Ed. 2004, 43,
6144e6146.
(m, 1H, C6H4), 7.49e7.52 (m, 2H, C6H4), 7.25e7.34 (m, 1H, C6H4),
2.65 (s, 3H, CH3C4O) ppm; 13C NMR (CDCl3, 75 MHz)
d
184.6, 154.0,
151.1, 136.3, 131.6, 131.3, 128.5, 127.7, 123.5, 121.5, 112.3, 10.1 ppm; IR
(KBr): 3645, 3194, 2962, 2916, 2850, 2349, 2308, 1732, 1651, 1587,
12. (a) Colobert, F.; Castanet, A. S.; Abillard, O. Eur. J. Org. Chem. 2005, 3334e3341;
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2006, 47, 5371e5373.
n
1556, 1504, 1454, 1394, 1296, 1263, 1070, 1012, 931, 875, 833,
742 cmꢁ1; HRMS (ESI) calcd for C16H11BrO2 ([MþH]þ) 314.9976,
found 315.0018.
Acknowledgements
16. Zhao, G.-L.; Huang, J. W.; Shi, M. Org. Lett. 2003, 24, 4737e4739.
17. Ko, K.; Nakano, K.; Watanabe, S.; Ichikawa, Y.; Kotsuki, H. Tetrahedron Lett. 2009,
4037e4041.
The authors thank National Natural Science Foundation of China
(Grant No. 20872001 and No. 20802002) and the Education Com-
mission of Anhui Province (Grant No. TD200707).
18. Sakakura, A.; Kawajiri, K.; Ohkubo, T.; Kosugi, Y.; Ishihara, K. J. Am. Chem. Soc.
2007, 129, 14775e14779.
€
19. (a) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751e2772; (b) Li, C.-J. Chem. Rev.
2005, 105, 3095e3166.
€
20. (a) Berkessel, A.; Groger, H. Asymmetric Organocatalysis; Wiley-VCH: New York,
NY, 2005; (b) Enantioselective Organocatalysis; Dalko, P. I., Ed.; Wiley-VCH: New
York, NY, 2007.
Supplementary data
21. Sheldon, R. A.; Ardens, I.; Hanefeld, U. Green Chemistry and Catalysis; Wiley-
VCH: Weinheim, Germany, 2007.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.09.095.
22. For the controversy regarding organocatalysis in aqueous media, see: (a) Bro-
gan, A. P.; Dickerson, T. J.; Janda, K. D. Angew. Chem., Int. Ed. 2006, 45,
8100e8102; (b) Hayashi, Y. Angew. Chem., Int. Ed. 2006, 45, 8103e8104; (c)
Blackmond, D. G.; Armstrong, A.; Coombe, V.; Wells, A. Angew. Chem., Int. Ed.
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