A mild and convenient one-pot two-step synthesis of hydroxy- iminodihydrobenzofurans mediated by silica gel under microwave activation conditions

Article abstract of DOI:10.1016/j.tet.2010.03.051

A convenient one-pot two-step procedure for the synthesis of hydroxyiminodihydrobenzofurans assisted by microwave irradiation in presence of silica gel is described herein. Cyclic 1,3-dicarbonyl compounds reacted smoothly with various nitroolefins to furn

Full text of DOI:10.1016/j.tet.2010.03.051

Tetrahedron 66 (2010) 3754–3760
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A mild and convenient one-pot two-step synthesis of hydroxy-
iminodihydrobenzofurans mediated by silica gel under microwave activation
conditions
*
Deepak Kumar Barange, B. Rama Raju, Veerababurao Kavala, Chun-Wei Kuo, Yu-Chen Tu, Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient one-pot two-step procedure for the synthesis of hydroxyiminodihydrobenzofurans assisted
by microwave irradiation in presence of silica gel is described herein. Cyclic 1,3-dicarbonyl compounds
reacted smoothly with various nitroolefins to furnish hydroxyiminodihydrobenzofuran derivatives as the
mixture of E and Z isomers. Clean reaction conditions, no work-up procedure, easy isolation and good
yields of the products are the salient features of the methodology.
Received 24 December 2009
Received in revised form 9 March 2010
Accepted 16 March 2010
Available online 20 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
studied the reaction of dimedone with aliphatic nitroolefin, which
has no a-alkyl substituent (1-nitro-propene). The product obtained
Benzofurans are highly valuable molecular motifs found in
various natural products.1 Most of the compounds containing
benzofuran framework exhibit interesting medicinal properties
and biological activities.2 In particular, tetrahydrobenzofurans are
an important class of heterocyclic compounds that can be found as
components in many life saving drugs. Moreover, these are also
extensively utilized as useful building blocks in the preparation of
a variety of natural products, such as evodone, pongamol, lanceo-
latin B, isoeupatin, tubipofurans, and paniculide A.3
In the view of their significance, several procedures toward the
synthesis of tetrahydrobenzofurans have been investigated for years.
The majority of approaches for the synthesis of tetrahydrobenzofur-
ans have been accomplished via ionic or radical pathways through
oxidative addition of 1,3-dicarbonyl compounds with the appropriate
olefins. Some of these routes employ substituted phenol derivatives
as the starting material.4 The initial report of the base-catalyzed
was the stereoisomeric mixture of (hydroxyimino)dihydrobenzofur-
ans.9 Recently, Ishikawa accomplished the synthesis of (hydrox-
yimino)dihydrobenzofuran derivatives by the conjugative addition of
cyclic 1,3-diones with various nitroalkenes.10 However, most of the
procedures employed for the synthesis of (hydroxyimino)dihy-
drobenzofurans involve the use of complex mixture of basic reagents
and also require tedious work-up procedures leading to the genera-
tion of a large amount of toxic waste.
Hence, an efficient and more convenient route for the synthesis
of (hydroxyimino)dihydrobenzofurans has still remained a task far
from perfection. The earlier reported methods suggest the syn-
thesis of (hydroxyimino)dihydrobenzofurans in the presence of
basic reagents or catalysts. In continuation of our research work on
functionalization of nitroolefins11 we were interested to investigate
the synthesis of (hydroxyimino)dihydrobenzofurans under mild
acidic catalyst. In the present days, many reports emerged in the
literature the use of silica gel as the vital promoter for various re-
actions.12 Moreover, the surface of silica gel is mild acidic13 in na-
ture, which not only acts as the acidic catalyst but also as an
activator for diverse organic transformations.14 The use of silica gel
has been highlighted due to its technical advantages such as high
surface area, insolubility in organic and aqueous solvents, thermal,
and mechanical stabilities.15
condensation of 1,3-cyclohexadione with
b-nitrostyrene and the
proposed structure for the product obtained remained unclear.5
Subsequently, some other groups investigated the same reaction
and suggested some probable structures for the above Michael ad-
duct.6 Later on, Jones and his co-workers successfully obtained the
cyclized product of the Michael adduct under mild basic conditions
and assigned the correct structure by crystallographic technique.7
The next development included the synthesis of 3-(4-Bromo-
phenyl)-6,7-dihydro-2-hydroxyiminobenzofuran-4(5H)-one from
the Michael adduct obtained from nitroolefin and cyclohexane-1,3-
dione catalyzed by the mild base.8 Yoshikoshi and his co-workers
Similarly, the application of microwave irradiation is a widely
accepted tool in organic synthesis due to its rate enhancements,
higher yields and often improved selectivity with respect to con-
ventional reaction conditions.16 Many reactions with great success
have been reported with microwave irradiation.17 In view of these
advantages, we would like to report the one-pot two-step synthesis
of hydroxyiminodihydrobenzofurans involving the Michael
* Corresponding author. Tel.: þ886 2 29309092; fax: þ886 2 29324249; e-mail
addresses: cheyaocf@ntnu.edu.tw, cheyaocf@yahoo.com.tw.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.051

D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
3755
addition of nitroalkenes with 1,3-dicarbonyl compounds followed
by intramolecular cyclization in presence of silica gel under mi-
crowave irradiation (Scheme 1).
sonication conditions, the yield of the product was improved to 80%
in 6 h (entry 3). The product yield was drastically increased to 91%
upon microwave irradiation with an excellent selectivity of E/Z (9:1)
(Table 1, entry 7). The earlier reported procedures also suggested the
formation of E isomer of hydroxyiminodihydrobenzofuran as the
major product in presence of base.8 In our study, we were able to
obtain the similar products ratios in the presence of mild acidic re-
agent. Under similar reaction conditions various other mild acidic
reagents, such as montmorillonite K-10, Amberlyst-15, and alumi-
num oxide were tested and found to be ineffective in terms of yields
and conversion. Hence, according to Table 1, the best yield of the
cyclized Michael adduct was accomplished with the acidic silica gel
in methanol under microwave irradiation conditions.
O
O
R
Silica Gel
NO2
N
+
R1
R2
R1
R2
R
MW 60 o
MeOH
C
O
OH
O
E 69% - 85%
0% - 8%
R = isopentyl, Ph-(CH2)2, Ph, 4-OMe-Ph,
4-Me-Ph, 4-SMe-Ph, 2-SMe-Ph,
4-Br-Ph, 4-Cl-Ph, 2-OCH3-Ph,
Z
3-CF3-Ph, 2-F-Ph, 2-furyl, 2-thienyl
R1 = R2 = H or Me
Scheme 1. Synthesis of 2-hydroxyimino-3-substituted-tetrahydrobenzofurans.
To explore the scope and limitations of this methodology, we
conducted the reaction of dimedone with various nitroolefins
under the optimized reaction conditions. It is evident from Table 2,
that the reaction proceeded smoothly with aliphatic and aromatic
2. Results and discussion
At the outset of our study, we examined the Michael reaction of
1-methyl-4-(2-nitrovinyl)benzene with dimedone (5,5-dime-
thylcyclohexane-1,3-dione) in aqueous medium under sonication
at room temperature conditions. The reaction proceeded well to
afford the Michael adduct in quantitative yield. Upon purification of
the crude reaction mixture by column chromatography, surpris-
ingly the cyclized product hydroxyiminodihydrobenzofuran of the
Michael adduct was obtained. This interesting result further
prompted us to investigate the appropriate conditions and the
reason for the formation of hydroxyiminodihydrobenzofuran.
We speculated that the mild acidic nature of the silica gel may be
the cause to affect the cyclization of the Michael adduct. Hence, we
conducted the reaction of 1-methyl-4-(2-nitrovinyl)benzene with
dimedone under the same reaction conditions in the presence of
silica gel. We were able to obtain quantitative yield of hydrox-
yiminodihydrobenzofuran as a mixture of isomers (Table 1, entry 1).
The 1H NMR spectra of the crude reaction mixture revealed a mix-
ture of E and Z isomers. The C-3 methine proton of the E isomer
exhibited a signal at 5.01 ppm and Z isomer displayed a signal at
4.93 ppm both in a ratio of (9:1), respectively. The structure as-
signment (E and Z) was in accordance with the reported literature.7
Encouraged by the above interesting results, we proceeded fur-
ther to optimize the reaction conditions to study the effect of solvent
and mild acidic heterogeneous medium by using the model reaction
of nitroolefin 1 and dimedone 2. When the reaction was performed
in presence of silica gel and methanol at room temperature stirring
only 30% of the product was obtained in 12 h (Table 1, entry 2). Under
Table 2
Synthesis of 3-substituted 6,7-dihydro-2-hydroxy iminobenzofuran-4-(5H)-one
O
O
O
R
R
OH
NO2
Silica gel, Methanol
MW, 60 o
N
N
C
O
OH
O
O
R
3a
1
2
3b
Entry
R
Time (h)
Yielda (%)
E
Z
1
2
5
6
68 (1a)
74 (2a)
d
d
2
6
82 (3a)
78 (4a)
8 (3b)
3
4
d
H3CO
5
6
4
5
85 (5a)
80 (6a)
6 (5b)
5 (6b)
H3C
H3CS
CH3
7
4
4
2
6
81 (7a)
68 (8a)
76 (9a)
76 (10a)
d
Table 1
Optimization of reaction conditions
8
d
Br
Cl
Me
O
O
9
6 (9b)
7 (10b)
NO2
Acidic Catalyst
N
Condition, solvent Me
Me
Me
Me
Me
O
3
OH
OCH3
O
1
2
10
Entry
Acidic catalyst
Solvent
Time (h)
Yielda % (E:Z)
1c
2b
3c
4d
5d
6d
7d
8d
Silica gel
Silica gel
Silica gel
Mont. K-10
Amberlyst-15
Al2O3
Water
10
12
6
12
12
12
4
77 (5:1)
30 (2:1)
80 (7:1)
30 (2:1)
45 (3:1.5)
40 (3:1)
91 (9:1)
11
12
1
1
82 (11a)
78 (12a)
6 (11b)
Methanol
Methanol
Methanol
Methanol
Methanol
Methanol
Methanol
F3C
F
d
Silica gel
d
1
Michael adduct
a
Isolated yields.
13
2
69 (13a)
d
b
c
Ambient conditions.
Sonication conditions.
Microwave conditions.
S
d
a
Isolated yields.

3756
D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
nitroolefins. Aliphatic nitroolefin, such as 4-methyl-1-nitropent-1-
ene reacted smoothly with dimedone under the present reaction
conditions to furnish the corresponding product favoring exclu-
sively the E isomer (Table 2, entry 1). The reaction time varied
according to the nature of the substituent on the aromatic nitro-
olefin. For example, the reaction of aromatic nitroolefin containing
the electron donating group, such as methyl and methoxy
required longer reaction times for the completion of the reaction
(entries 4, 5, 7, and 10). Whereas, the reaction of b-nitrostyrenes
bearing electron-withdrawing groups, such as bromo, chloro,
fluoro, and trifluoromethyl required short reaction times to afford
their corresponding dihydroxyiminodihydrobenzofuran-4(5H)-
ones in good yields (Table 2, entries 8, 9, 11, and 12). Acid sensitive
moieties like thiophene also survived under the present reaction
conditions.
Similarly, 1,3-cyclohexadione reacted efficiently with various
nitroolefins to afford the corresponding products in good yields
(Table 3, entries 1–8). The b-diketones to undergo this reaction are
Figure 1. X-ray crystal structure of (Z)-2-(hydroxyimino)-6,6-dimethyl-3-phenyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (ORTEP view).18
dimedone and cyclohexe-1,3-dione. The reaction failed with
1,3-cyclopentadione. It is noteworthy that hydroxyimino dihydo-
benzofuran derivatives upon long standing on the column silica gel
bed undergo slow isomerization to E isomer from the Z form during
the purification process. The single crystal X-ray structure of the E
and Z adducts is shown in Figure 1 and 2, respectively.
Table 3
Synthesis of 3-substituted 3,5,6,7-dihydro-2-hydroxyiminobenzofuran-4(5H)-one
O
O
O
R
R
NO
Silica gel
OH
N
N
MW 60 C,
Methanol
R
O
O
ivb
OH
O
iva
iii
Entry
R
Time (h)
Yielda (%)
E
Z
1
2
5
4
72 (14a)
70 (15a)
d
8 (15b)
3
4
5
8
4
5
82 (16a)
78 (17a)
75 (18a)
5 (16b)
5 (17b)
6 (18b)
H3CO
H3C
Figure 2. X-ray crystal structure of (E)-2-(hydroxyimino)-6,6-dimethyl-3-phenyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (ORTEP view).18
applicability to cyclic
b-diketones. The reason may be due to the
instability of the cyclized Michael adduct or lesser reactivity of
H3CS
acyclic 1,3-dicarbonyl compounds with the
b-nitrostyrene.
O O2N
Me
O
6
7
1
6
80 (19a)
78 (20a)
6 (19b)
8 (20b)
NO2
Me
Me
silica gel, methanol
MW 60oC, 2h
F
+
Me
O
O
(vii)
(v)
(vi)
yield: 85%
OCH3
Scheme 2. Michael reaction of pentane-2,4-dione and
b-nitrostyrene.
Cl
8
2
85 (21a)
5 (21b)
One of the major advantages of this protocol is the simple
isolation and purification. After completion of the reaction, the
silica gel was filtered and the solvent was evaporated to obtain the
crude product, which was purified by column chromatography.
Hence no work-up procedure was necessary, the silica gel
obtained as the residue was washed with methanol for several
times and activated in the oven for the next cycle. After each
recycle the loss of activity was observed with diminishing product
yields.
a
Isolated yield.
There are also structural limitations in the reactant 1,3-dicar-
bonyl compounds. Under similar reaction conditions the reaction of
-nitrostyrene with the aliphatic 1,3-dicarbonyl compound, such as
pentane-2,4-dione afforded only the Michael adduct in good yeild
(Scheme 2). No cylcised adduct was observed with aliphatic
1,3-dicarbonyl substrates. Hence this methodology limits its
b

D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
3757
O
O
4.2.1. (E)-2-(Hydroxyimino)-3-isobutyl-6,6-dimethyl-2,3,6,7-tetra-
R'
O
N
hydrobenzofuran-4(5H)-one (1a). White solid; mp: 145–147 ꢀC. IR
O
O
Si
R
N
O
R
(NaCl) n
/cmꢁ1: 3270, 2864, 1628, 1394, 949. 1H NMR (DMSO-d6)
R'
OH
A
O
Si
O
O
O
R
OH
R
d
10.35 (s, 1H), 3.70–3.66 (m, 1H), 2.54 (d, J¼17.6 Hz, 1H), 2.50 (dd,
J¼17.6, 2.2 Hz, 1H), 2.20 (d, J¼16.0 Hz, 1H), 2.19 (d, J¼16.0 Hz, 1H),
1.87–1.83 (m, 1H), 1.63–1.56 (m, 1H), 1.52–1.46 (m, 1H), 1.04 (s, 6H),
0.64 (s, 3H), 0.65 (s, 3H). 13C NMR (DMSO-d6)
d 193.1, 171.0, 156.6,
O
O
O
R'
R'
R'
115.8, 50.7, 40.7, 37.6, 35.8, 33.8, 28.0, 27.7, 24.2, 23.2, 21.5. MS (EI)
(m/z) (relative intensity) 251 (Mþ, 10), 234 (20), 195 (100), 178 (15).
HRMS calcd for C14H21NO3 (Mþ) 251.1512, found 251.1512.
H
O
N
OH
O
R
N
R
R
N
O
-H2SiO3
O
O
O
O Si
R
R
R
OH
C
B
4.2.2. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-phenethyl-2,3,6,7-tetra-
Scheme 3. Plausible mechanism of the reaction.
hydrobenzofuran-4(5H)-one (2a). White solid; mp: 130–132 ꢀC. IR
(NaCl) n d 10.49 (s,
/cmꢁ1: 3294, 2922, 1639, 951. 1H NMR (DMSO-d6)
We speculate that silica gel may activate the nitro group of
nitroalkene thereby generating an electron deficient carbon at
2-position of the b-nitroalkene. This species was attacked by the
diketone to form intermediate (A), which undergoes intra-
molecular cyclization to generate intermediate (B). Intermediate B
upon losing H2SiO3 molecule to generate nitroso compound (C).
This nitroso compound tautomerises to give the 2-hydroxyimino-
3-substituted-tetrahydrobenzofuran (Scheme 3).
1H), 7.28–7.23 (m, 2H), 7.18–7.08 (m, 3H), 3.78–3.37 (m, 1H), 2.61–
2.57 (m, 2H), 2.56 (d, J¼17.2 Hz,1H), 2.52 (dd, J¼17.2, 2.5 Hz,1H), 2.19
(d, J¼16.0 Hz, 1H), 2.21 (d, J¼16.0 Hz, 1H), 2.02–1.97 (m, 2H), 1.07 (s,
3H),1.05 (s, 3H). 13C NMR (DMSO-d6) 193.2,171.4,156.2,141.2,128.8,
128.1,128.0,127.3,114.9, 50.6, 35.8, 33.7, 32.7, 31.0, 27.9, 27.8. MS (EI)
(m/z) (relative intensity) 299 (Mþ, 65), 255 (23), 207 (44), 194 (100),
178 (48). HRMS calcd for C18H21NO3 (Mþ) 299.1516, found 299.1528.
4.2.3. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-phenyl-2,3,6,7-tetrahy-
3. Conclusion
drobenzofuran-4(5H)-one (3a). White solid; mp: 132–134 ꢀC. IR
(NaCl)
d 10.18 (s, 1H), 7.28–7.26 (m, 2H), 7.22–7.20 (m, 3H), 5.01 (s, 1H),
n
/cmꢁ1: 3293, 2869, 1647, 1391, 954. 1H NMR (DMSO-d6)
In summary, we have developed a simple and efficient pro-
cedure for the synthesis of 2-hydroxyimino-3-substituted-tetra-
hydrobenzofuran derivatives in the presence of acidic silica gel.
Operational simplicity, inexpensive reagents, and good yields of the
products are the key advantages over the existing methods.
2.74 (d, J¼17.2 Hz, 1H), 2.62 (dd, J¼17.2, 2.4 Hz, 1H), 2.21 (d,
J¼16.1 Hz, 1H), 2.15 (d, J¼16.1 Hz, 1H), 1.08 (s, 3H), 1.06 (s, 3H). 13C
NMR (DMSO-d6) d 192.4, 172.1, 156.3, 139.0, 128.4, 127.5, 127.1, 115.6,
50.7, 44.8, 35.8, 33.8, 28.0, 27.0. MS (EI) (m/z) (relative intensity) 272
((Mþ1)þ, 30), 271 (Mþ, 100), 254.1 (83), 240 (38). HRMS calcd for
C16H17NO3 (Mþ) 271.1203, found 271.1203.
4. Experimental
4.1. General
4.2.4. (Z)-2-(Hydroxyimino)-6,6-dimethyl-3-phenyl-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (3b). White solid; mp: 154–156 ꢀC. IR
All the reactions were performed in oven (130 ꢀC) dried glass-
ware under an inert atmosphere of argon unless otherwise speci-
fied. Solvents for extraction and chromatography were distilled
before use. All the chemicals used in this study were of commercial
grade and used after distillation. Analytical thin layer chromatog-
raphy was performed with E. Merck silica gel 60 F254 aluminum
plates. All purifications were carried out by flash chromatography
using 230–400 mesh silica gel. 1H and 13C NMR were recorded with
Bruker Avance EX 400 FT NMR. Chemical shifts were reported in
(NaCl) n d 10.46
/cmꢁ1: 3267, 1636, 1391, 1030. 1H NMR (DMSO-d6)
(s, 1H), 7.32 (t, J¼7.3 Hz, 2H), 7.24 (t, J¼7.3 Hz, 1H), 7.19 (d, J¼6.9 Hz,
2H), 4.93 (s, 1H), 2.74 (d, J¼17.4 Hz, 1H), 2.64 (dd, J¼17.4, 2.4 Hz,
2H), 2.27 (d, J¼16.2 Hz, 1H), 2.21 (d, J¼16.2 Hz, 1H), 1.08 (s, 3H), 1.06
(s, 3H). 13C NMR (DMSO-d6)
d 191.7, 172.2, 165.2, 136.5, 128.2, 127.8,
126.8, 116.5, 50.6, 38.8, 35.8, 33.8, 28.1, 27.8.
4.2.5. (E)-2-(Hydroxyimino)-3-(4-methoxyphenyl)-6,6-dimethyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (4a). White solid; mp:
parts per million (
d) using TMS as internal standard and coupling
142–144 ꢀC. IR (NaCl) /cmꢁ1: 3350, 2803, 1639, 1391, 1030. 1H NMR
n
constants were expressed in hertz. Mass spectra were obtained on
a JOEL SX-102A spectrometer at an ionization potential of 70 eV and
data are reported as mass/charge (m/z) with the percent relative
abundance. High-resolution mass spectra (HRMS) were acquired
with a FINNIGAN MAT-95XL spectrometer. Microwave reactions
were carried out in a commercially available monomode system
(CEM Discover). The reactor has a variable power output from 0 to
300 W.
(DMSO-d6)
d
10.40 (s, 1H), 7.09 (d, J¼8.6 Hz, 2H), 6.87 (d, J¼8.6 Hz,
2H), 4.86 (s, 1H), 3.74 (s, 3H), 2.68 (d, J¼18.0 Hz, 1H), 2.56 (dd,
J¼17.9, 2.4 Hz, 1H), 2.24 (d, J¼15.9 Hz, 1H), 2.18 (d, J¼15.9 Hz, 1H),
1.10 (s, 3H), 1.09 (s, 3H). 13C NMR (DMSO-d6)
d 192.4, 171.8, 158.3,
156.5, 130.9, 128.5, 115.7, 113.8, 55.0, 50.7, 44.0, 35.8, 33.8, 28.0, 27.9.
MS (EI) (m/z) (relative intensity) 301 (Mþ, 100), 284 (85), 271 (30),
217 (10). HRMS calcd for C17H19NO4 (Mþ) 301.1304, found 301.1301.
4.2.6. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-p-tolyl-2,3,6,7-tetrahy-
4.2. General procedure for the synthesis of 2-hydroxyimino-
3-substituted-tetrahydrobenzofurans
drobenzofuran-4(5H)-one (5a). White solid; mp: 178–180 ꢀC. IR
(NaCl) n
/cmꢁ1: 3271, 2925, 1636, 1392, 1030. 1H NMR (DMSO-d6)
d
10.17 (s, 1H), 7.07–7.12 (m, 4H), 4.98 (s, 1H), 2.68 (d, J¼17.9 Hz, 1H),
A mixture of
b-nitrostyrene 1 (1.2 mmol) and 1,3-dicarbonyl
2.57 (dd, J¼17.8, 2.0 Hz,1H), 2.27 (s, 3H), 2.18 (d, J¼16.2 Hz,1H), 2.13
compound 2 (1 mmol) was added into a thick walled glass vial
containing 500 mg of silica gel and 4 mL of methanol. The reaction
mixture in the microwave reactor was heated to 60 ꢀC. The progress
of the reaction was monitored by TLC. After completion, methanol
was evaporated under reduced pressure. The crude reaction mix-
ture was adsorbed in silica gel and was purified by column chro-
matography to obtain the pure product. Both the E and Z isomers
were separated by column chromatography.
(d, J¼16.2 Hz, 1H) 1.08 (s, 3H), 1.07 (s, 3H). 13C NMR (DMSO-d6)
d
191.7, 172.0, 165.3, 135.9, 133.5, 128.7, 127.6, 116.6, 50.6, 44.0, 35.8,
33.8, 28.1, 27.7, 20.5. MS (EI) (m/z) (relative intensity) 285 (Mþ, 100),
268 (98), 254 (39), 201 (30). HRMS calcd for C17H19NO3 (Mþ)
285.1365, found 285.1362.
4.2.7. (Z)-2-(Hydroxyimino)-6,6-dimethyl-3-p-tolyl-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (5b). White solid; mp: 172–174 ꢀC. IR

3758
D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
(NaCl)
n
/cmꢁ1: 3270, 1635, 1391, 1172, 1003. 1H NMR (DMSO-d6)
2H), 4.98 (s, 1H), 2.68 (d, J¼16.4 Hz, 1H), 2.57 (dd, J¼16.4, 2.4 Hz,
1H), 2.28 (d, J¼16.2 Hz, 1H), 2.23 (d, J¼16.2 Hz, 1H), 1.14 (s, 3H), 1.09
(s, 3H). 13C NMR (DMSO-d6) 191.7, 172.4, 164.8, 135.5, 131.4, 129.6,
128.4, 116.2, 50.5, 43.8, 35.8, 33.8, 28.0, 27.8.
d
10.39 (s, 1H), 7.11–7.03 (m, 4H), 4.85 (s, 1H), 2.25 (s, 3H), 2.69 (d,
J¼17.9 Hz, 1H), 2.52 (dd, J¼17.8, 2.0 Hz, 1H), 2.22 (d, J¼16.1 Hz, 1H),
2.20 (d, J¼16.1 Hz, 1H), 1.11 (s, 3H), 1.09 (s, 3H). 13C NMR (DMSO-d6)
192.3, 171.9, 156.4, 136.1, 136.0, 128.9, 127.3, 115.7, 50.6, 44.4, 35.8,
33.8, 27.9, 20.5, 14.0.
4.2.14. (E)-2-(Hydroxyimino)-3-(2-methoxyphenyl)-6,6-di methyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (10a). White solid; mp:
4.2.8. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-(4-(methylthio)
nyl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (6a). White solid; mp:
162–164 ꢀC. IR (NaCl) /cmꢁ1: 3272, 2924, 1635, 1391, 1031. 1H NMR
(DMSO-d6) 10.21 (s, 1H), 7.18–7.13 (m, 4H), 4.98 (s, 1H), 2.65 (d,
phe-
149–151 ꢀC. IR (NaCl) /cmꢁ1: 3271, 2924, 1638, 1392, 1031. 1H NMR
n
(DMSO-d6) d 9.88 (s, 1H), 7.19–7.07 (m, 2H), 6.97–6.83 (m, 2H), 5.75
n
(s, 1H), 3.72 (s, 3H), 2.59 (d, J¼17.4 Hz, 1H), 2.56 (dd, J¼17.4, 2.4 Hz,
d
1H), 2.17 (d, J¼15.9 Hz, 1H), 2.11 (d, J¼15.9 Hz, 1H), 1.04 (s, 3H), 0.97
J¼17.9 Hz, 1H), 2.56 (dd, J¼17.8, 2.0 Hz, 1H), 2.43 (s, 3H), 2.15 (d,
(s, 3H). 13C NMR (DMSO-d6)
d 191.5, 172.1, 165.3, 156.7, 156.5, 130.2,
J¼16.1 Hz, 1H), 2.13 (d, J¼16.1 Hz, 1H), 1.07 (s, 3H), 1.05 (s, 3H). 13C
128.0, 124.9, 120.2, 111.2, 55.5, 50.6, 40.8, 35.9, 33.8, 28.5, 27.0. MS
(EI) (m/z) (relative intensity) 302 (Mþ1,18), 301 (Mþ, 65), 284 (100),
228 (15).
NMR (DMSO-d6) d 191.8,172.3,165.1,136.4,133.2,128.4,125.8,116.4,
50.6, 43.9, 35.8, 28.1, 27.8, 14.7. MS (EI) (m/z) (relative intensity) 317
(Mþ, 100), 300 (22), 253 (30). HRMS calcd for C17H19NO3S (Mþ)
317.1080, found 317.1091.
4.2.15. (Z)-2-(Hydroxyimino)-3-(2-methoxyphenyl)-6,6-dimethyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (10b). White solid; mp:
4.2.9. (Z)-2-(Hydroxyimino)-6,6-dimethyl-3-(4-(methylthio)
nyl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (6b). White solid; mp:
147–149 ꢀC. IR (NaCl) /cmꢁ1: 3372, 2925, 1638, 1388, 956 cmꢁ1. 1H
NMR (DMSO-d6)
J¼8.0 Hz, 2H), 4.86 (s, 1H), 2.60 (s, 3H), 2.69 (d, J¼18.0 Hz, 1H), 2.56
(dd, J¼18.0, 2.1 Hz, 2H), 2.24 (d, J¼16.0 Hz, 1H), 2.19 (d, J¼16.0 Hz,
1H), 1.11 (s, 3H), 1.09 (s, 3H). 13C NMR (DMSO-d6) 192.3, 172.0, 156.2,
136.8, 135.6, 128.0, 126.1, 115.5, 50.6, 44.3, 35.8, 33.8, 27.9, 14.7.
phe-
181–183 ꢀC. IR (NaCl) /cmꢁ1: 3308, 2923, 1643, 1391, 952. 1H NMR
n
(DMSO-d6)
d
10.18 (s, 1H), 7.24–7.20 (m, 1H), 7.10 (d, J¼7.4 Hz, 1H),
n
6.97 (d, J¼8.0 Hz, 1H), 6.89–6.85 (m, 1H), 4.98 (s, 1H), 3.72 (s, 3H),
2.64 (d, J¼17.2 Hz, 1H), 2.50 (dd, J¼17.2, 2.3 Hz, 1H), 2.17 (d,
J¼16.0 Hz, 1H), 2.03 (d, J¼16.0 Hz, 1H), 1.09 (s, 3H), 1.07 (s, 3H). 13C
d
10.40 (s, 1H), 7.11 (d, J¼8.0 Hz, 2H), 7.04 (d,
NMR (DMSO-d6)
d 192.2, 171.8, 156.7, 156.5, 129.4, 128.4, 126.8,
120.2, 115.0, 111.5, 55.5, 50.7, 40.9, 35.9, 33.8, 28.3, 27.4.
4.2.16. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-(3-(trifluoro methyl)-
4.2.10. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-o-tolyl-2,3,6,7-tetra-
phenyl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (11a). White solid;
hydrobenzofuran-4(5H)-one (7a). White solid; mp: 171–173 ꢀC. IR
mp: 139–141 ꢀC. IR (NaCl) /cmꢁ1: 3309, 2933, 1641, 1394, 942. 1H
n
(NaCl)
d6)
n
/cmꢁ1: 3373, 2945, 1638, 1358, 956 cmꢁ1. 1H NMR (DMSO-
NMR (DMSO-d6) d 10.30 (s, 1H), 7.58–7.52 (m, 4H), 5.23 (s, 1H), 2.69
d
10.40 (s, 1H), 7.19–6.94 (m, 3H), 6.93 (d, J¼7.8 Hz, 1H), 2.76 (d,
(d, J¼16.2 Hz, 1H), 2.59 (dd, J¼16.2, 2.2 Hz, 1H), 2.45 (d, J¼15.8 Hz,
J¼18.2 Hz,1H), 2.56 (dd, J¼18.2, 2.3 Hz,1H), 5.12 (s,1H), 2.42 (s, 3H),
2.46 (d, J¼15.9 Hz, 1H), 2.22 (d, J¼15.9 Hz, 1H), 1.14 (s, 3H), 1.10 (s,
1H), 2.17 (d, J¼15.8 Hz, 1H), 1.08 (s, 3H), 1.06 (s, 3H). 13C NMR
(DMSO-d6)
d 191.8, 172.6, 165.0, 156.0, 136.5, 132.9, 128.7, 127.6 (q,
3H). 13C NMR (DMSO-d6)
d
192.3, 172.0, 156.5, 137.3, 135.8, 130.4,
J¼2.0 Hz),126.4 (q, J¼6.0 Hz),125.9 (q, J¼272.0 Hz),115.8, 50.6, 41.2,
35.8, 33.7, 27.9, 27.6. MS (EI) (m/z) (relative intensity) 339 (Mþ, 100),
322 (62), 255 (38). HRMS calcd for C17H16FNO3 (Mþ) 339.1077,
found 339.1085.
126.9, 126.0, 115.8, 50.6, 41.8, 35.8, 33.9, 28.2, 27.9, 19.3. MS (EI) (m/
z) (relative intensity) 285 (Mþ, 100), 268 (90) 183 (45). HRMS calcd
for C17H19NO3 (Mþ) 285.1359, found 285.1359.
4.2.11. (E)-3-(4-Bromophenyl)-2-(hydroxyimino)-6,6-dimethyl-
4.2.17. (E)-3-(2-Fluorophenyl)-2-(hydroxyimino)-6,6-dimethyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (8a). Brown solid; mp:
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (12a). White solid; mp:
142–144 ꢀC. IR (NaCl)
n
/cmꢁ1: 3352, 2922, 1637, 1399, 1031 cmꢁ1
.
138–140 ꢀC. IR (NaCl) /cmꢁ1: 3307, 2927, 1647, 1374, 956, 759.
n
1H NMR (DMSO-d6)
d
10.25 (s, 1H), 7.47 (d, J¼8.4 Hz, 2H), 7.17 (dd,
1H NMR (DMSO-d6)
d 10.17 (s, 1H), 7.28–7.23 (m, 2H), 7.13–7.08
J¼8.4 Hz, 2H), 5.04 (s, 1H), 2.66 (d, J¼17.8 Hz, 1H), 2.57 (dd, J¼17.8,
2.3 Hz, 1H), 2.18 (d, J¼16.1 Hz, 1H), 2.14 (d, J¼16.1 Hz, 1H), 1.07 (s,
3H), 1.05 (s, 3H). 13C NMR (DMSO-d6) 191.7, 172.4, 164.7, 136.0,
131.0, 130.0, 119.8, 116.1, 50.6, 43.9, 35.8, 33.8, 28.0, 27.8. MS (EI)
(m/z) (relative intensity) 299 (Mþ, 65), 255 (23), 207 (44), 194
(100), 178 (48). HRMS calcd for C16H16BrNO3 (Mþ) 349.0308, found
349.0308.
(m, 2H), 5.16 (s, 1H), 2.63 (d, J¼16.4 Hz, 1H), 2.62 (dd, J¼16.4,
2.3 Hz. 1H), 2.19 (d, J¼16.0 Hz, 1H), 2.10 (d, J¼16.0 Hz, 1H), 1.05
(s, 3H), 1.02 (s, 3H). 13C NMR (DMSO-d6)
d 191.6, 172.6, 164.6,
159.8 (d, J¼244.0 Hz), 130.0 (d, J¼13.0 Hz), 128.9 (d, J¼8.2 Hz),
124.3, 115.4, 115.0 (d, J¼22.0 Hz), 50.5, 38.7, 33.9, 29.3, 28.2, 27.4.
MS (EI) (m/z) (relative intensity) 289.0 (Mþ, 100), 272 (78), 236
(42), 204 (62). HRMS calcd for C16H16FNO3 (Mþ) 289.1142, found
289.1155.
4.2.12. (E)-3-(4-Chlorophenyl)-2-(hydroxyimino)-6,6-dimethyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (9a). White solid; mp:
4.2.18. (Z)-3-(2-Fluorophenyl)-2-(hydroxyimino)-6,6-dimethyl-
158–160 ꢀC. IR (NaCl)
n
/cmꢁ1: 3166, 2924, 1640, 1391, 1016 cmꢁ1. 1H
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (12b). White solid; mp:
NMR (400 MHz, DMSO-d6)
d
10.26 (s, 1H), 7.34 (d, J¼8.0 Hz, 2H),
144–146 ꢀC. IR (NaCl) /cmꢁ1: 3280, 2923, 1641, 1392, 956. 1H NMR
n
7.23 (dd, J¼8.1 Hz, 2H), 5.06 (s, 1H), 2.66 (d, J¼17.4 Hz, 1H), 2.57 (dd,
(DMSO-d6) d 10.44 (s, 1H), 7.31–7.28 (m, 1H), 7.25–7.21 (m, 1H),
J¼17.4, 2.2 Hz, 1H), 2.18 (d, J¼16.4 Hz, 1H), 2.14 (d, J¼16.4 Hz, 1H),
7.21–7.18 (m, 2H), 5.09 (s, 1H), 2.68 (d, J¼17.8 Hz, 1H), 2.58 (dd,
1.07 (s, 3H), 1.06 (s, 3H). 13C NMR (DMSO-d6)
d 192.4, 172.3, 155.9,
J¼17.8, 2.4 Hz, 1H), 2.19 (d, J¼16.4 Hz, 1H), 2.10 (d, J¼16.4 Hz, 1H),
137.9, 131.7, 129.4, 128.4, 115.3, 50.6, 44.1, 35.8, 33.8, 28.0, 27.9. MS
(EI) (m/z) (relative intensity) 305 (Mþ, 100), 288.0 (58), 252.1 (32),
221.0 (38). HRMS calcd for C16H16ClNO3 (Mþ) 305.0815, found
305.0815.
1.09 (s, 3H), 1.07 (s, 3H). 13C NMR (DMSO-d6)
d 191.8, 173.7, 161.2,
157.4 (d, J¼243.0 Hz), 129.8, 129.2 (d, J¼9.0 Hz), 125.8 (d,
J¼13.0 Hz), 115.7, 115.5 (d, J¼22.0 Hz), 50.5, 38.7, 33.9, 29.3, 28.2,
27.4.
4.2.13. (Z)-3-(4-Chlorophenyl)-2-(hydroxyimino)-6,6-dimethyl-
4.2.19. (E)-2-(Hydroxyimino)-6,6-dimethyl-3-(thiophen-2-yl)-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (9b). White solid; mp:
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (13a). Brown solid; mp:
151–153 ꢀC. IR (NaCl)
n
/cmꢁ1: 3277, 2924, 1638, 1391, 1031. 1H NMR
160–162 ꢀC. IR (NaCl) /cmꢁ1: 3246, 2854,1635,1392,1030. 1H NMR
n
(DMSO-d6)
d
10.49 (s, 1H), 7.37 (d, J¼8.0 Hz, 2H), 7.20 (d, J¼8.0 Hz,
(DMSO-d6)
d
10.45 (s, 1H), 7.35 (d, J¼4.0 Hz, 1H), 6.95–6.92 (m, 2H),

D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
3759
5.35 (s, 1H), 2.67 (d, J¼17.3 Hz, 1H), 2.62 (dd, J¼17.3, 2.4 Hz, 1H),
2.24 (d, J¼16.0 Hz, 1H), 2.18 (d, J¼16.0 Hz, 1H), 1.10 (s, 3H), 1.09 (s,
(m, 5H), 2.08–2.07 (m, 2H). 13C NMR (DMSO-d6)
156.2, 136.2, 135.9, 128.7, 127.3, 116.8, 44.5, 36.4, 22.5, 20.9, 20.6.
d
192.9, 173.3,
3H). 13C NMR (DMSO-d6)
d 192.1, 173.1, 164.1, 138.9, 127.0, 126.9,
125.1, 116.4, 51.0, 36.3, 34.3, 28.8, 27.9. MS (EI) (m/z) (relative in-
tensity) 277 (Mþ, 58), 260 (100), 247 (30). HRMS calcd for
C14H15NO3S (Mþ) 277.0765, found 277.0766.
4.2.27. (E)-2-(Hydroxyimino)-3-(4-(methylthio)phenyl)-2,3,6,7-tet-
rahydrobenzofuran-4(5H)-one (18a). White solid; mp: 172–174 ꢀC.
IR (NaCl)
10.22 (s, 1H), 7.25–7.12 (m, 4H), 4.98 (s, 1H), 2.78–2.63 (m, 2H),
n
/cmꢁ1: 3283, 2922, 1645, 1391, 953. 1H NMR (DMSO-d6)
d
4.2.20. (E)-2-(Hydroxyimino)-3-isobutyl-2,3,6,7-tetrahydro benzo-
2.44 (s, 3H), 2.26–2.23 (m, 2H), 2.04–2.02 (m, 2H). 13C NMR (DMSO-
d6) 199.0, 168.4, 148.6, 140.2, 131.7, 130.2, 125.8, 124.5, 87.2, 42.5,
36.6, 19.6, 14.2. MS (EI) (m/z) (relative intensity) 289 (Mþ1, 100),
272 (85), 236 (30), 205 (80). HRMS calcd for C15H15NO3S (Mþ)
289.0767, found 289.0780.
furan-4(5H)-one (14a). White solid; mp: 138–140 ꢀC. IR (NaCl)
n
/cmꢁ1: 3265, 2945, 1627, 1395, 949. 1H NMR (DMSO-d6)
d 10.35 (s,
1H), 3.67–3.64 (m, 2H), 2.30–2.26 (m, 2H), 2.01–1.98 (m, 2H), 1.90–
1.86 (m, 1H), 1.64–1.57 (m, 1H), 1.50–1.45 (m, 2H), 0.85 (s, 3H), 0.84
(s, 3H). 13C NMR (DMSO-d6)
d 193.6, 172.3, 156.3, 117.1, 40.8, 37.7,
36.4, 24.1, 23.1, 22.8, 20.9. MS (EI) (m/z) (relative intensity) 224
(Mþ1, 38), 206 (22), 166 (100), 149 (43), 136 (18). HRMS calcd for
C12H17NO3 223.1208, found 223.1210.
4.2.28. (Z)-2-(Hydroxyimino)-3-(4-(methylthio)phenyl)-2,3,6,7-tet-
rahydrobenzofuran-4(5H)-one (18b). White solid; mp: 163–165 ꢀC.
IR (NaCl)
(DMSO-d6)
(m, 2H), 2.44 (s, 3H), 2.26–2.04 (m, 2H), 2.03–1.98 (m, 2H). 13C NMR
(DMSO-d6) 192.3, 173.7, 164.8, 136.4, 133.1, 128.5, 126.1, 125.8,
n
/cmꢁ1: 3284, 2676, 2945, 1678, 1341, 1093. 1H NMR
d
10.19 (s, 1H), 7.18–7.16 (m, 4H), 4.95 (s, 1H), 2.74–2.69
4.2.21. (E)-2-(Hydroxyimino)-3-phenyl-2,3,6,7-tetrahydro benzofu-
ran-4(5H)-one (15a). White solid; mp: 149–151 ꢀC. IR (NaCl)
d
n
/cmꢁ1: 3272, 2922, 1634, 1361, 1003 cmꢁ1
.
1H NMR (400 MHz,
117.6, 43.9, 36.4, 22.4, 20.9, 14.7.
DMSO-d6)
d 10.17 (s, 1H), 7.29–7.17 (m, 5H), 4.98 (s, 1H), 2.79–2.69
(m, 2H), 2.32–2.26 (m, 2H), 2.06–1.98 (m, 2H). 13C NMR (100 MHz,
4.2.29. (E)-3-(2-Fluorophenyl)-2-(hydroxyimino)-2,3,6,7-tetrahy-
DMSO-d6)
d
192.3, 172.6, 164.9, 136.4, 128.1, 127.9, 126.8, 117.7, 44.4,
drobenzofuran-4(5H)-one (19a). White solid; mp: 150–152 ꢀC. IR
36.4, 22.4, 20.9. MS (EI) (m/z) (relative intensity) 243 (Mþ, 100), 226
(85), 212 (42), 187 (38). HRMS calcd for C14H13NO3 (Mþ) 243.0890,
found 243.0895.
(NaCl)
10.16 (s, 1H), 7.28–7.22 (m, 2H), 7.12–7.08 (m, 2H), 5.14 (s, 1H),
2.78–2.70 (m, 2H), 2.25–2.21 (m, 2H), 2.08–2.01(m, 2H). 13C NMR
(DMSO-d6)
n
/cmꢁ1: 3386, 2920, 1636, 1392, 1003. 1H NMR (DMSO-d6)
d
d
192.2, 173.9, 164.4, 161.2 (d, J¼245.0 Hz), 129.8, 128.8
4.2.22. (Z)-2-(Hydroxyimino)-3-phenyl-2,3,6,7-tetrahydro benzofu-
(d, J¼8.0 Hz), 124.3, 123.9 (d, J¼13.0 Hz), 116.6, 115.2 (d, J¼21.0 Hz),
38.4, 36.3, 22.5, 20.9. MS (EI) (m/z) (relative intensity) 262 (Mþ1,
20), 261 (Mþ, 100), 244 (30), 205 (62). HRMS calcd for C14H12FNO3
(Mþ) 261.0796, found 261.0807.
ran-4(5H)-one (15b). White solid; mp: 155–157 ꢀC. IR (NaCl)
n
/cmꢁ1: 3367, 2921, 1643, 1391, 955. 1H NMR (DMSO-d6)
d
10.40 (s,
1H), 7.65–7.17 (m, 5H), 4.87 (s,1H), 3.29–2.69 (m, 2H), 2.52–2.33 (m,
2H), 2.12–1.98 (m, 1H). 13C NMR (DMSO-d6)
192.3, 172.6, 164.9,
d
136.4, 128.1, 127.9, 126.8, 117.7, 44.4, 36.4, 22.4, 20.9.
4.2.30. (Z)-3-(2-Fluorophenyl)-2-(hydroxyimino)-2,3,6,7-tetra hy-
drobenzofuran-4(5H)-one (19b). White solid; mp: 141–143 ꢀC. IR
4.2.23. (E)-2-(Hydroxyimino)-3-(4-methoxyphenyl)-2,3,6,7-tetrahy-
(NaCl)
10.43 (s, 1H), 7.33–7.27 (m, 1H), 7.24–7.15 (m, 1H), 7.15–7.08 (m,
2H), 5.06 (s, 1H), 2.75–2.69 (m, 2H), 2.30–2.27 (m, 2H), 2.09–1.98
(m, 2H). 13C NMR (DMSO-d6)
193.3, 174.2, 161.7, 159.2 (d,
n
/cmꢁ1: 3274, 2918, 1639, 1390, 957. 1H NMR (DMSO-d6)
drobenzofuran-4(5H)-one (16a). White solid; mp: 170–172 ꢀC. IR
d
(NaCl)
d6)
10.14 (s, 1H), 7.13 (d, J¼8.5 Hz, 2H), 6.82 (d, J¼8.4 Hz, 2H), 4.92
(s, 1H), 2.78–2.67 (m, 2H), 2.32–2.26 (m, 2H), 2.04–2.01 (m, 2H). 13C
NMR (DMSO-d6) 192.9,173.4,158.1,156.3,131.5,128.5,128.3,116.9,
n
/cmꢁ1: 3283, 2928, 1639, 1511, 1391, 955. 1H NMR (DMSO-
d
d
J¼244.0 Hz), 130.3, 129.7 (d, J¼9.0 Hz), 126.3 (d, J¼13.0 Hz), 116.2,
d
116.1 (d, J¼22.0 Hz), 38.6, 36.8, 23.0, 21.4.
113.7, 113.5, 113.1, 55.0, 44.1, 36.5, 22.5, 20.9. MS (EI) (m/z) (relative
intensity) 273 (Mþ, 100), 256 (70), 243 (24). HRMS calcd for
C15H15NO5 (Mþ) 273.0996, found 273.0997.
4.2.31. (E)-2-(Hydroxyimino)-3-(2-methoxyphenyl)-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (20a). White solid; mp: 162–163 ꢀC. IR
(NaCl) n
/cmꢁ1: 3283, 2917, 1637, 1390, 954. 1H NMR (DMSO-d6)
4.2.24. (Z)-2-(Hydroxyimino)-3-(4-methoxyphenyl)-2,3,6,7-tetrahy-
d
9.87 (s, 1H), 7.23–7.14 (m, 1H), 7.05 (d, J¼8.2 Hz, 1H), 6.96 (d,
drobenzofuran-4(5H)-one (16b). White solid; mp: 145–147 ꢀC. IR
J¼8.2 Hz, 1H), 6.86 (d, J¼8.3 Hz, 1H), 5.07 (s, 1H), 3.74 (s, 3H), 2.70–
(NaCl)
n
/cmꢁ1: 3404, 2911, 1636, 1510, 1393, 1172 cmꢁ1
.
1H NMR
2.63 (m, 2H), 2.27–2.22 (m, 2.H), 2.08–2.01 (m, 2H). 13C NMR
(DMSO-d6)
d
10.36 (s, 1H), 7.14–7.08 (m, 2H), 6.86–6.81 (m, 2H),
(DMSO-d6) d 192.2, 173.3, 165.2, 156.8, 129.0, 128.4, 128.0, 120.3,
4.81 (s,1H), 3.71 (s, 3H), 2.74–2.68 (m, 2H), 2.30–2.23 (m, 2H), 2.06–
1.98 (m, 2H). 13C NMR (DMSO-d6) 193.0, 173.5, 165.1, 158.1, 130.9,
128.9, 117.7, 113.5, 55.0, 43.6, 36.4, 22.4, 20.9.
116.2, 55.8, 38.8, 36.5, 22.5, 21.0. MS (EI) (m/z) (relative intensity)
273 (Mþ, 45), 256 (100), 228 (25), 214 (14). HRMS calcd for
C15H15NO4 (Mþ) 273.0996, found 273.1006.
4.2.25. (E)-2-(Hydroxyimino)-3-p-tolyl-2,3,6,7-tetrahydro benzofu-
4.2.32. (Z)-2-(Hydroxyimino)-3-(2-methoxyphenyl)-2,3,6,7-tetrahy-
ran-4(5H)-one (17a). White solid; mp: 180–182 ꢀC. IR (NaCl)
drobenzofuran-4(5H)-one (20b). White solid; mp: 170–171 ꢀC. IR
n
/cmꢁ1: 3252, 2918, 1635, 1391, 956. 1H NMR (DMSO-d6)
d
10.15 (s,
(NaCl) n
/cmꢁ1: 3400, 2921, 1638, 1390, 954. 1H NMR (DMSO-d6)
1H), 7.13 (d, J¼8.0 Hz, 1H), 7.06 (d, J¼8.0 Hz, 1H), 4.95 (s, 1H), 2.79–
d
10.20 (s, 1H), 7.21 (d, J¼7.7 Hz, 1H), 7.06 (d, J¼7.2 Hz, 1H), 6.97 (d,
2.63 (m, 2H), 2.26–2.25 (m, 2H), 2.23 (s, 3H), 2.05–1.99 (m, 2H). 13C
J¼8.2 Hz, 1H), 6.86 (d, J¼7.3 Hz, 1H), 4.99 (s, 1H), 3.74 (s, 3H), 2.72–
NMR (DMSO-d6)
d
192.3, 173.5, 165.0, 135.9, 133.4, 128.7, 127.7, 117.7,
2.63 (m, 2H), 2.27–2.24 (m, 2H), 2.08–2.03 (m, 2H). 13C NMR
44.0, 36.4, 22.4, 20.9, 20.6. MS (EI) (m/z) (relative intensity) 257
(Mþ, 100), 240 (96), 226 (50), 201 (30). HRMS calcd for C15H15NO3
(Mþ) 257.1046, found 257.1045.
(DMSO-d6) d 192.7, 173.4, 165.1, 156.3, 129.9, 128.0, 127.0, 120.3,
116.2, 111.7, 55.7, 38.8, 36.5, 30.6, 21.0.
4.2.33. (E)-3-(4-Chlorophenyl)-2-(hydroxyimino)-2,3,6,7-tetrahy-
4.2.26. (Z)-2-(Hydroxyimino)-3-p-tolyl-2,3,6,7-tetrahydro benzofu-
drobenzofuran-4(5H)-one (21a). White solid; mp: 145–146 ꢀC. IR
ran-4(5H)-one (17b). White solid; mp: 162–163 ꢀC. IR (NaCl)
(NaCl)
10.25 (s, 1H), 7.33 (d, J¼8.0 Hz, 2H), 7.25 (d, J¼8.0 Hz, 2H), 5.02 (s,
1H), 2.74–2.69 (m, 2H), 2.08–2.06 (m, 2H), 2.08–2.03 (m, 2H). 13C
n
/cmꢁ1: 3271, 2922, 1637, 1390, 1004. 1H NMR (DMSO-d6)
n
/cmꢁ1: 3261, 2918, 1637, 1388, 954. 1H NMR (DMSO-d6)
d
10.36 (s,
d
1H), 7.10–7.04 (m, 4H), 4.81 (s, 1H), 2.81–2.69 (m, 2H), 2.34–2.25

3760
D.K. Barange et al. / Tetrahedron 66 (2010) 3754–3760
5. Stetter, H.; Hoehne, K. Chem. Ber. 1958, 91, 1344–1347.
NMR (DMSO-d6) d 192.8,174.4,165.0,135.9,131.9,130.3,128.5,117.8,
6. Nielsen, A. T.; Archibald, T. G. Tetrahedron 1969, 25, 2393–2400.
7. Dominianni, S. J.; Chaney, M. O.; Jones, N. D. Tetrahedron Lett. 1970, 54, 4735–
4736.
8. Ansell, G. B.; Moore, D. W.; Nielsen, A. T. J. Chem. Soc. B 1971, 2376–2382.
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11. (a) Tu, Z.; Raju, B. R.; Liou, T.-R.; Kavala, V.; Kuo, C.-W.; Jang, Y.; Shih, Y.-H.; Yao,
C.-F. Tetrahedron 2009, 65, 2436–2442; (b) Chu, C.-M.; Tu, Z.; Wu, P.; Wang,
C.-C.; Liu, J.-T.; Kuo, C.-W.; Yao, C.-F. Tetrahedron 2009, 65, 3878–3885; (c)
Barange, D. K.; Kavala, V.; Kuo, C.-W.; Tseng, C.; Tu, Y.-C.; Yao, C.-F. Tetrahedron
Lett. 2009, 50, 5116–5119; (d) Habib, P. M.; Kavala, V.; Kuo, C.-W.; Yao, C.-F.
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hedron Lett. 2001, 42, 3613–3615; (f) Yao, C.-F.; Chu, C.-M.; Liu, J.-T. J. Org. Chem.
1998, 63, 719–722; (g) Liu, J.-T.; Lin, W.-W.; Jang, J.-J.; Liu, J.-Y.; Yan, M.-C.; Hung,
C.; Kao, K.-H.; Wang, Y.; Yao, C.-F. Tetrahedron 1999, 55, 7115–7128; (h) Yao, C.-
F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Lin, Y.-M.; Lin, W.-W.;
Yan, M.-C.; Liu, J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791–822.
12. (a) Ramazani, A.; Mahyari, A. T.; Rouhani, M.; Rezaei, A. Tetrahedron Lett. 2009,
50, 5625–5627; (b) You, L.; Feng, S.; An, R.; Wang, X.; Bai, D. Tetrahedron Lett.
2008, 49, 5147–5149; (c) Mangu, N.; Kaiser, H. M.; Kar, A.; Spannenberg, A.;
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44.3, 22.9, 21.4, 21.2. MS (EI) (m/z) (relative intensity) 277 (Mþ,100),
220 (50), 190 (25). HRMS calcd for C14H12ClNO3 (Mþ) 277.0500,
found 277.0511.
4.2.34. (Z)-3-(4-Chlorophenyl)-2-(hydroxyimino)-2,3,6,7-tetra hy-
drobenzofuran-4(5H)-one (21b). White solid; mp: 168–170 ꢀC. IR
(NaCl)
d6)
10.15 (s, 1H), 7.13 (d, J¼8.4 Hz, 2H), 6.82 (d, J¼8.6 Hz, 2H), 4.90
(s, 1H), 2.78–2.67(m, 2H), 2.26–2.23 (m, 2H), 2.04–1.99 (m, 2H). 13C
NMR (DMSO-d6) 193.0, 173.9, 164.5, 137.9, 135.4, 131.6, 129.8,
n
/cmꢁ1: 3272, 2925, 2698, 1638, 1388, 956. 1H NMR (DMSO-
d
d
116.4, 44.2, 36.4, 22.5, 20.9.
4.2.35. 3-(1-Nitro-2-phenylethyl)pentane-2,4-dione
(vii). White
solid; mp: 100–102 ꢀC. IR (NaCl) /cmꢁ1: 2924, 1644, 1375, 1167,
n
1003. 1H NMR (DMSO-d6)
d 7.45–7.24 (m, 5H), 4.82–4.73 (m, 2H),
4.09–4.03 (m 1H), 4.65 (d, J¼8.0 Hz, 1H), 2.23 (s, 3H), 1.89 (s, 3H).
13C NMR (DMSO-d6) 201.8, 201.7, 136.9, 128.6, 128.3, 127.7, 78.2,
68.9, 42.9, 30.7, 30.6. HRMS calcd for C13H15NO4 (Mþ) 249.1001,
found 249.1006.
13. (a) Pindur, U.; Lutz, G.; Otto, C. Chem. Rev. 1993, 93, 741–761; (b) Corma, A.;
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S. L.; Crawford, S. D.; Durland, W. F., Jr.; Jones, J. E., III; Raleigh, J. S. J. Org. Chem.
1995, 60, 4146–4152 and references cited therein.
Acknowledgements
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Financial support of this work by National Science Council of the
Republic of China and National Taiwan Normal University is
gratefully acknowledged.
References and notes
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18. CCDC number of the anti and syn adducts are 725383 and 725385 respectively.
These data can be obtained free of charge from Cambridge Crystallographic
Data Center via www.ccdc.cam.ac.uk/datarequest/cif.