Iodine(III)-mediated tandem oxidative cyclization for construction of 2-nitrobenzo[ b ]furans

Article abstract of DOI:10.1021/jo301162x

Various 3-alkyl-2-nitrobenzo[b]furans were synthesized from common intermediate 2-(2-nitroethyl)phenols via a hypervalent iodine-induced oxidative cyclization, with good to excellent yields. This facile route is able to efficiently functionalize 2-nitrobenzo[b]furans, which are difficult to obtain by classical methods.

Full text of DOI:10.1021/jo301162x

Note
pubs.acs.org/joc
Iodine(III)-Mediated Tandem Oxidative Cyclization for Construction
of 2‑Nitrobenzo[b]furans
Shi-Chao Lu,† Pu-Rong Zheng,† and Gang Liu*,†,‡,§
†Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Road, Xicheng
Dist., Beijing 100050, People’s Republic of China
§
‡Tsinghua-Peking Center for Life Sciences and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine,
Tsinghua University, Haidian Dist., Beijing 100084, People’s Republic of China
S
* Supporting Information
ABSTRACT: Various 3-alkyl-2-nitrobenzo[b]furans were synthesized from common intermediate 2-(2-nitroethyl)phenols via a
hypervalent iodine-induced oxidative cyclization, with good to excellent yields. This facile route is able to efficiently functionalize
2-nitrobenzo[b]furans, which are difficult to obtain by classical methods.
present major disadvantages of poor regioselectivity and low
ynthesis of benzo[b]furans has drawn extensive and
Senduring attention because of their ubiquitous and varied yield.4 An improved method was reported that 2-trimethyl-
biological activities.1,2 In particular, the synthesis of 3-alkyl-2-
stannylated benzo[b]furan can be converted to 2-nitrobenzo-
[b]furan upon treatment with tetranitromethane, but pre-
functionalization of the benzo[b]furan was needed (Figure 1,
route c).5 Very recently, Wunderlich et al. reported an
alternative approach by reaction of diorganozinc compounds
bearing a nitro group with an alkyl halide. The reaction was
catalyzed by (tmp)2Zn·2MgCl2·2LiCl and highly toxic regent
CuCN·2LiCl (Figure 1, route d).6 Thus, the development of
new methods for efficient construction of 3-alkyl-2-nitrobenzo-
[b]furans is quite desirable. In this paper, we report a facile
synthesis of 3-alkyl-2-nitrobenzo[b]furans via tandem iodine-
(III)-induced oxidative cyclization and subsequent dehydrogen-
ation.
nitrobenzo[b]furans is the subject of intense investigation
because the nitro group has a significant effect on the biological
activity and often manifests changes in chemical and physical
properties.3 Unfortunately, as Figure 1 indicates, the synthetic
methods are not well-developed. The condensation of
bromonitromethane and ortho-hydroxylated aromatic aldehydes
is generally used to prepare 2-nitrobenzofurans, but not for the
preparation of 3-substituted 2-nitrobenzofurans (Figure 1,
route a).3c Direct nitration methods (Figure 1, route b)
In the past decades, the chemistry of hypervalent iodine
organic compounds has experienced explosive developments.7
In particular, aryl-λ3-iodanes (iodine in the oxidation state +III)
have been established as cheap and nontoxic alternatives to
transition metals in oxidative C−H bond activations.8,9 Inspired
by the metal-free oxidative C−H activation approaches, we
proposed that the desired 3-alkyl-2-nitrobenzo[b]furan prod-
ucts could be obtained by hypervalent iodine through the
intramolecular cyclization and subsequent dehydrogenation of
2-(2-nitroethyl)phenols. The substituents at the 3-position of 2-
nitrobenzo[b]furans are able to be easily introduced by the
well-known Michael addition of a nucleophilic reagent to a
nitroolefin (Scheme 1).10
In our initial studies, we chose the 2-(2-nitroethyl)phenol 1a
(prepared by Michael addition of the corresponding
Received: June 12, 2012
Published: August 1, 2012
Figure 1. Methods for the synthesis of 2-nitrobenzo[b]furans.
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
active species of hypervalent iodine reagents through the
combination of TBAI with tert-butyl hydroperoxide (TBHP) or
H2O2.13 However, the desired reaction failed to take place;
instead, trans-2-nitro-2,3-dihydrobenzofuran 3a was selectively
obtained in excellent yield (Table 1, entries 6 and 7).
Stereochemical assignment of the obtained compound was
based on the 1H NMR coupling constants. The coupling
constants of the isolated product 3a were measured to be 1.4
Hz, matching the values of known trans-isomers (J = 1.0−2.0
Hz).14 In the case of the corresponding syn-isomers, J values are
known to be in the range of 6.5−8.0 Hz. Consequently, the
trans-isomer was obtained exclusively, but these tested
conditions lack a dehydrogenation step.
Scheme 1. Synthetic Route for 2-Nitrobenzo[b]furan
Formation
nucleophilic reagent to 2-nitrovinylbenzene) as a model
substrate to examine whether the substrate 1a could be
converted into the corresponding nitrobenzofuran 2a (Table
1). Reaction was carried out in CH3CN at 35 °C in the
Surprisingly, when a base such as NaOAc, K2CO3, t-BuOK,
or, in particular, Et3N (Table 1, entries 8−11) was added to the
reaction mixture, the yield of 2a was significantly increased to
91%. Addition of acetic acid resulted in a nearly complete loss
of reactivity (Table 1, entry 12). It is assumed that the base
promoted the deprotonation of the nitroalkane at the α-
position to form the corresponding resonance-stabilized anion
and neutralized the acetic acid produced in the reaction.
The effect of solvents on the model reaction was further
examined. Among the solvents tested, in addition to CH3CN,
CH2Cl2 and dioxane are also acceptable while H2O and MeOH
are not (Table 1, entries 13−17).
Under the optimized reaction conditions, the scope and
generality of the reaction were systematically investigated. The
results listed in Table 2 demonstrate that the corresponding
target products were obtained in good to excellent yields for
most substrates. It was observed that substrate 1d, without any
substitution at the position of R2, produced the 2-nitro-
benzofuran 2d in 91% yield by this method. To check the effect
of R2 substituents, various substrates bearing different
substituted aliphatic (Table 2, 2a−2c, 2e−2o) and aromatic
(Table 2, 2p−2s) motifs at this position were converted to the
desired products 2 in satisfactory yields. These results also show
that when R2 was a bulkier benzyl group (Table 2, 2h−2o) or
phenyl (Table 2, 2p−2s), the reaction yields were slightly
reduced.
Table 1. Screening of the Reaction Conditions
a
yield (%)
TBAI/hypervalent iodine
b
entry
(equiv)
solvent
additive
2a
3a
1
2
3
4
5
PIDA (1)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
0
0
26
0
TBAI/PIDA (1:1)
30
trace
trace
55
0
TBAI/PIFA (1:1)
TBAI/HTIB (1:1)
0
TBAI/PIDA (2.5:3.0)
TBAI/TBHP (0.1:1)
TBAI/H2O2 (0.1:1)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
TBAI/PIDA (2.5:3.0)
30
94
95
20
10
12
<5
18
8
c
6
7
8
0
NaOAc
K2CO3
t-BuOK
Et3N
71
65
67
91
8
9
10
11
12
13
14
15
16
17
AcOH
Et3N
88
76
0
CH2Cl2
CH3OH
H2O
Et3N
10
0
Et3N
To obtain further insights into the reaction mechanism,
compound 3a was treated with the combination of PhI(OAc)2
(1 equiv)/TBAI (1 equiv)/Et3N (1 equiv) under the same
conditions, and it could be converted smoothly into product 2a
in 90% yield (Scheme 2). This suggested that the oxidation
system of PhI(OAc)2/TBAI played an important role for
dehydrogenation of 3a.
Et3N
0
0
dioxane
Et3N
86
6
a
b
Isolated yields after silica gel chromatography. Relative to amount of
c
1a. The reaction was carried out at 80 °C.
presence of 1 equiv of PhI(OAc)2 as the oxidant (Table 1, entry
1). However, none of the desired product was observed; the
majority of the starting material 1a remained. To generate a
more reactive hypervalent iodine species, 1 equiv of
tetrabutylammonium iodide (TBAI) was added.11 After an
initial screen of typical aryl-λ3-iodanes (PhI(OAc)2 (PIDA),
PhI(OCOCF3)2 (PIFA), and PhI(OH)(OTs) (HTIB)) as
oxidants (Table 1, entries 2−4), we found that the combination
of TBAI with PhI(OAc)2 successfully produced 2a in 30% yield
(Table 1, entry 2) while a 2-nitro-2,3-dihydrobenzofuran
product 3a was also isolated in 26% yield. With exposure of
substrate 1a to 2.5 equiv of PhI(OAc)2 and 3 equiv of TBAI in
CH3CN for 30 min, the yields of 2a and 3a were increased to
55 and 30%, respectively (Table 1, entry 5). It is hypothesized
that the required excess of PhI(OAc)2 and moderate yield is
most likely the result of the generation of unreactive I2.12
Motivated by the synthetic potential of the possible method, we
further employed conditions that generated in situ catalytically
On the basis of this observation and the literature evidence,12
a plausible reaction pathway for the PhI(OAc)2/Bu4NI-
mediated tandem oxidative cyclization is formulated in Scheme
3. It is assumed that PhI(OAc)2 initially reacts with TBAI to
give a halide-exchanged halonium species A. Under basic
conditions, deprotonation of the nitroalkane at the α-position
forms the corresponding resonance-stabilized anion B. Anion B
with the generated highly reactive iodine species A forms an α-
hyperiodination intermediate C, which is ready to undergo an
intramolecular attack on the α-position of the nitro group by
the oxygen atom to give 3-alkyl-2-nitro-2,3-dihydrobenzofuran
D accompanied by reductive elimination of PhI. Following a
second α-hyperiodination and subsequent reductive elimina-
tion, 3-alkyl-2-nitrobenzofuran is finally formed.
A valuable benefit of this tandem reaction is shown by its
application to highly functionalized molecules such as a
coumarin derivative and an indole derivative (Scheme 4). 3,3-
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Note
a
Table 2. Synthesis of 3-Alkyl-2-nitrobenzo[b]furans by Iodine(III)-Mediated Tandem Oxidative Cyclization
a
All reactions were run under the following conditions, unless otherwise indicated: substrates 1 (1.0 mmol), PhI(OAc)2 (3.0 mmol), TBAI (2.5
mmol), Et3N (2.0 mmol) at 35 °C in CH3CN (3 mL) under argon atmosphere. Yield of analytically pure product.
transformation, various 2-nitrobenzo[b]furan derivatives were
efficiently converted into 3-substituted 2-nitrobenzo[b]furans
in good to excellent yields. The present process could facilitate
the synthetic applications of nitro-containing building blocks.
Scheme 2. Control Experiment
EXPERIMENTAL SECTION
■
Preparation of Substrates 1a−1c, 1e−1h, 1l−1o, and 1s.
Three milliliters of Grignard reagent (1.0 M solution in THF) was
slowly added to corresponding 2-nitroethene (1.0 mmol) in 20 mL of
anhydrous THF at −30 °C under argon atmosphere. After 30 min, an
ice-cold 5% aqueous HCl (15 mL) was then added to the reaction
solution and stirred for 30 min. The reaction mixture was extracted
with ethyl acetate and dried over MgSO4. The solvent was evaporated
to give the crude product. Further purification was achieved by column
chromatography on silica gel (ethyl acetate/petroleum).
Linked hybrid molecules of indole and benzofuran pharmaco-
phores were obtained for the first time (Scheme 4, 2t). From
coumain substrate 4, designed furocoumarin 2u was obtained in
two steps in moderate yield. These results illustrate that indole
and coumarin, involving an α,β-unsaturated system and an ester
bond, tolerate a mild TBAI/PhI(OAc)2/Et3N system. The
coumarin ring and indole, present in natural products and
displaying interesting pharmacological properties, have in-
trigued medicinal chemists to explore and synthesize their
analogues for use as drugs. The diversity shown by our
synthetic route may lead to interesting derivatives and
biological activity.
2-Methoxy-6-(1-nitrohexan-2-yl)phenol (1a): Colorless oil,
197 mg, 78% yield; H NMR (300 MHz, acetone) δ 7.64 (s, 1H),
1
6.88−6.85 (m, 1H), 6.79−6.76 (m, 2H), 4.88−4.72 (m, 2H), 3.85−
3.78 (m, 4H), 1.93−1.62 (m, 2H), 1.37−1.14 (m, 4H), 0.83 (t, J = 6.8
Hz, 3H); 13C NMR (150 MHz, acetone) δ 148.2, 145.3, 126.4, 121.5,
120.1, 110.7, 80.0, 56.2, 40.0, 31.9, 30.0, 23.1, 14.1; HRMS (ESI-TOF)
calcd for C13H19NO4Na [M + Na]+ (276.1206), found 276.1217.
2-(1-Cyclohexyl-2-nitroethyl)phenol (1b): Colorless oil, 174
CONCLUSION
1
■
mg, 70% yield; H NMR (300 MHz, acetone) δ 8.48 (s, 1H), 7.12−
In conclusion, we have presented a highly efficient and practical
protocol for synthesis of 3-alkyl-2-nitrobenzo[b]furans by
iodine(III)-mediated tandem oxidative cyclization. In this
7.05 (m, 3H), 6.84 (d, J = 8.0 Hz, 1H), 6.78 (t, J = 7.4 Hz, 1H), 5.03−
4.88 (m, 2H), 3.58 (m, 1H), 1.96−0.93 (m, 11H); 13C NMR (150
MHz, acetone) δ 156.1, 130.6, 128.7, 126.5, 120.3, 116.3, 116.2, 78.3,
7713
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Note
Scheme 3. Proposed Mechanistic Pathway
Scheme 4. Application for Synthesis of More Complex Molecules
46.4, 40.3, 31.7, 31.6, 27.0, 26.9, 26.8; HRMS (ESI-TOF) calcd for
C14H19NO3Na [M + Na]+ (272.1257), found 272.1250.
4-Bromo-2-methoxy-6-(1-nitrohexan-2-yl)phenol (1g): Col-
orless oil, 265 mg, 80% yield; 1H NMR (300 MHz, acetone) δ 7.99 (s,
1H), 7.01 (d, J = 1.9 Hz, 2H), 6.98 (d, J = 1.9 Hz, 1H), 4.92−4.75 (m,
2H), 3.94−3.72 (m, 4H), 1.77−1.65 (m, 2H), 1.37−1.13 (m, 4H),
0.84 (t, J = 7.0 Hz, 3H); 13C NMR (150 MHz, acetone) δ 149.2,
144.9, 128.6, 124.0, 114.1, 111.4, 79.6, 56.6, 39.7, 31.9, 30.3, 23.1, 14.1;
HRMS (ESI-TOF) calcd for C13H18BrNO4Na [M + Na]+ (354.0311),
found 354.0325.
2-(1-Nitrohexan-2-yl)phenol (1c): Colorless oil, 167 mg, 75%
1
yield; H NMR (300 MHz, acetone) δ 8.56 (s, 1H), 7.16 (d, J = 7.8
Hz, 1H), 7.08 (t, J = 7.8 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 6.81 (t, J =
7.5 Hz, 1H), 4.86 (dd, J = 12.2, 8.1 Hz, 1H), 4.75 (dd, J = 12.2, 7.1 Hz,
1H), 3.88−3.72 (m, 1H), 1.81−1.90 (m, 1H), 1.80−1.62 (m, 1H),
1.36−1.16 (m, 4H), 0.83 (t, J = 6.9 Hz, 3H); 13C NMR (150 MHz,
acetone) δ 156.0, 129.8, 128.8, 126.7, 120.5, 116.4, 80.0, 40.2, 31.8,
29.9, 23.1, 14.1; HRMS (ESI-TOF) calcd for C12H17NO3Na [M +
Na]+ (246.1101), found 246.1113.
2-Methoxy-6-(3-methyl-1-nitrobutan-2-yl)phenol (1e): Col-
orless oil, 206 mg, 86% yield; 1H NMR (300 MHz, acetone) δ 7.58 (s,
1H), 6.86−6.82 (m, 1H), 6.76−6.74 (m, 2H), 5.02−4.87 (m, 2H),
3.83 (s, 3H), 3.58−3.53 (m, 1H), 2.18−2.10 (m, 1H), 1.04 (d, J = 6.7
Hz, 3H), 0.81 (d, J = 6.7 Hz, 3H); 13C NMR (150 MHz, acetone) δ
148.1, 145.3, 126.3, 122.1, 120.0, 110.6, 78.4, 56.2, 46.9, 30.8, 21.2,
20.8; HRMS (ESI-TOF) calcd for C12H17NO4Na [M + Na]+
(262.1050), found 262.1060.
2-(1-Nitro-3-phenylpropan-2-yl)phenol (1h): Colorless oil, 198
1
mg, 77% yield; H NMR (300 MHz, DMSO) δ 9.59 (s, 1H), 7.26−
6.97 (m, 7H), 6.76 (d, J = 7.5 Hz, 1H), 6.67 (t, J = 7.4 Hz, 1H), 4.92
(dd, J = 12.5, 9.0 Hz, 1H), 4.70 (dd, J = 12.5, 6.1 Hz, 1H), 4.02−3.89
(m, 1H), 3.02 (dd, J = 13.6, 8.2 Hz, 1H), 2.90 (dd, J = 13.6, 7.1 Hz,
1H); 13C NMR (150 MHz, acetone) δ 155.1, 139.0, 128.9, 128.7,
128.2, 128.0, 126.1, 125.1, 118.9, 115.3, 78.3, 40.5, 37.1; HRMS (ESI-
TOF) calcd for C15H15NO3Na [M + Na]+ (280.0944), found
280.0957.
2-Methoxy-6-(1-nitro-3-p-tolylpropan-2-yl)phenol (1l): Col-
orless oil, 262 mg, 87% yield; 1H NMR (300 MHz, acetone) δ 7.72 (s,
1H), 7.09−7.01 (m, 4H), 6.83 (dd, J = 6.5, 2.9 Hz, 1H), 6.75−6.69
(m, 2H), 4.96 (dd, J = 12.5, 8.9 Hz, 1H), 4.71 (dd, J = 12.5, 6.1 Hz,
1H), 4.15−4.03 (m, 1H), 3.82 (s, 3H), 3.13 (dd, J = 13.7, 8.0 Hz, 1H),
2.98 (dd, J = 13.7, 7.5 Hz, 1H), 2.25 (s, 3H); 13C NMR (150 MHz,
acetone) δ 148.2, 145.2, 136.9, 136.4, 129.8, 129.7, 126.1, 121.7, 120.0,
110.9, 78.8, 56.2, 42.4, 37.8, 21.0; HRMS (ESI-TOF) calcd for
C17H19NO4Na [M + Na]+ (324.1206), found 324.1216.
2-(1-Cyclohexyl-2-nitroethyl)-6-methoxyphenol (1f): Color-
1
less oil, 229 mg, 82% yield; H NMR (300 MHz, acetone) δ 7.55 (s,
1H), 6.83−6.78 (m, 1H), 6.71−6.67 (m, 2H), 4.93−4.88 (m, 2H),
3.79 (s, 3H), 3.60−3.53(m, 1H), 1.95−0.83 (m, 11H); 13C NMR (150
MHz, acetone) δ 148.1, 145.4, 126.1, 122.3, 119.4, 110.6, 78.3, 56.2,
46.1, 40.3, 31.71, 31.65, 30.0, 26.9, 26.8; HRMS (ESI-TOF) calcd for
C15H21NO4Na [M + Na]+ (302.1363), found 302.1369.
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Note
2-Methoxy-6-(1-nitro-3-phenylpropan-2-yl)phenol (1m):
Colorless oil, 470 mg, two steps, yield 82%; H NMR (300 MHz,
gain pure product. Subsequent deprotection of methyl group was
processed as previously described in ref 15.
1
acetone) δ 7.75 (s, 1H), 7.27−7.15 (m, 5H), 6.86−6.82 (m, 1H),
6.74−6.69 (m, 2H), 4.98 (dd, J = 12.5, 8.9 Hz, 1H), 4.74 (dd, J = 12.5,
6.2 Hz, 1H), 4.17−4.04 (m, 1H), 3.82 (s, 3H), 3.17 (dd, J = 13.7, 8.1
Hz, 1H), 3.03 (dd, J = 13.6, 7.3 Hz, 1H); 13C NMR (150 MHz,
acetone) δ 148.2, 145.2, 140.0, 129.9, 129.1, 127.1, 126.0, 121.7, 120.0,
111.0, 78.8, 56.2, 42.4, 38.2; HRMS (ESI-TOF) calcd for
C16H17NO4Na [M + Na]+ (310.1050), found 310.1058.
4-Chloro-2-(1-nitro-3-p-tolylpropan-2-yl)phenol (1n): Color-
less oil, 427 mg, two steps, yield 70%; 1H NMR (300 MHz, acetone) δ
8.95 (s, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.12−7.01 (m, 5H), 6.86 (d, J =
8.6 Hz, 1H), 5.00 (dd, J = 12.6, 9.1 Hz, 1H), 4.74 (dd, J = 12.6, 5.9 Hz,
1H), 4.13−4.01 (m, 1H), 3.12 (dd, J = 13.7, 8.0 Hz, 1H), 3.00 (dd, J =
13.7, 7.5 Hz, 1H), 2.25 (s, 3H); 13C NMR (150 MHz, acetone) δ
154.9, 136.6, 136.5, 129.80, 129.77, 128.8, 128.7, 124.6, 117.8, 78.5,
42.3, 37.7, 20.9; HRMS (ESI-TOF) calcd for C16H16ClNO3Na [M +
Na]+ (328.0711), found 328.0704.
2-(1-(2-Fluorophenyl)-3-nitropropan-2-yl)phenol (1i): Color-
less oil, 407 mg, two steps, yield 74%; 1H NMR (300 MHz, acetone) δ
8.66 (s, 1H), 7.25−7.12 (m, 2H), 7.12−6.96 (m, 4H), 6.84 (d, J = 7.9
Hz, 1H), 6.73 (t, J = 7.5 Hz, 1H), 5.04 (dd, J = 12.5, 8.7 Hz, 1H), 4.81
(dd, J = 12.6, 6.3 Hz, 1H), 4.17−4.04 (m, 1H), 3.26−3.11 (m, 2H);
13C NMR (150 MHz, acetone) δ 162.1 (d, J = 243.0), 156.0, 132.4 (d,
J = 5.0 Hz), 130.3, 129.20 (d, J = 8.1 Hz), 129.19, 126.8 (d, J = 15.3
Hz), 125.9, 124.9, 120.5, 116.4, 115.8, 78.9, 41.7, 31.4 (d, J = 22.0 Hz);
HRMS (ESI-TOF) calcd for C15H14FNO3Na [M + Na]+ (298.0850),
found 298.0862.
2-(1-(4-Fluorophenyl)-3-nitropropan-2-yl)phenol (1j): Color-
less oil, 434 mg, two steps, yield 79%; 1H NMR (300 MHz, acetone) δ
8.65 (s, 1H), 7.21−7.14 (m, 2H), 7.05 (t, J = 7.2 Hz, 2H), 6.96 (t, J =
8.8 Hz, 2H), 6.85 (d, J = 7.6 Hz, 1H), 6.73 (t, J = 7.5 Hz, 1H), 4.99
(dd, J = 12.5, 8.7 Hz, 1H), 4.79 (dd, J = 12.5, 6.4 Hz, 1H), 4.11−3.97
(m, 1H), 3.17 (dd, J = 13.6, 8.4 Hz, 1H), 3.05 (dd, J = 13.7, 6.9 Hz,
1H); 13C NMR (150 MHz, acetone) δ 162.3 (d, J = 240.0 Hz), 156.0
(d, J = 2.8 Hz), 136.1, 131.6 (d, J = 7.2 Hz), 130.2, 129.1, 126.0, 120.5,
116.4, 115.6 (d, J = 22.0 Hz), 78.9, 42.8, 37.3; HRMS (ESI-TOF)
calcd for C15H14FNO3Na [M + Na]+ (298.0850), found 298.0861.
2-(1-(2-Chlorophenyl)-3-nitropropan-2-yl)-6-methoxyphe-
4-Bromo-2-(1-nitro-3-p-tolylpropan-2-yl)phenol (1o): Color-
1
less oil, 290 mg, 83% yield; H NMR (300 MHz, acetone) δ 8.98 (s,
1H), 7.29 (d, J = 2.4 Hz, 1H), 7.20 (dd, J = 8.6, 2.5 Hz, 1H), 7.11−
7.03 (m, 4H), 6.82 (d, J = 8.6 Hz, 1H), 5.00 (dd, J = 12.7, 9.1 Hz, 1H),
4.74 (dd, J = 12.7, 5.9 Hz, 1H), 4.13−4.00 (m, 1H), 3.12 (dd, J = 13.7,
7.9 Hz, 1H), 3.00 (dd, J = 13.7, 7.6 Hz, 1H), 2.25 (s, 3H); 13C NMR
(150 MHz, acetone) δ 155.5, 136.7, 132.8, 131.8, 129.9, 129.4, 118.5,
112.0, 78.6, 42.4, 37.8, 21.1; HRMS (ESI-TOF) calcd for
C16H16BrNO3Na [M + Na]+ (372.0206), found 372.0209.
1
nol (1k): Colorless oil, 462 mg, two steps, yield 72%; H NMR (300
MHz, acetone) δ 7.76 (s, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.22−7.10 (m,
3H), 6.86−6.79 (m, 1H), 6.73−6.68 (m, 2H), 5.06 (dd, J = 12.5, 8.8
Hz, 1H), 4.81 (dd, J = 12.5, 6.3 Hz, 1H), 4.25−4.13 (m, 1H), 3.82 (s,
4H), 3.27 (d, J = 7.7 Hz, 2H); 13C NMR (150 MHz, acetone) δ 148.2,
145.4, 137.5, 134.7, 132.3, 130.2, 129.0, 127.7, 125.5, 122.1, 120.0,
111.2, 78.8, 56.2, 41.2, 35.8; HRMS (ESI-TOF) calcd for
C16H16ClNO4Na [M + Na]+ (344.0660), found 344.0665.
Preparation of Substrate 1d. Cmopound 1d was synthesized
following known procedure.17
2-(2-Nitroethyl)phenol (1d): Colorless oil, 155 mg, 93% yield;
1H NMR (300 MHz, acetone) δ 8.61 (s, 1H), 7.15−7.06 (m, 2H),
6.87 (d, J = 8.0 Hz, 1H), 6.78 (t, J = 7.4 Hz, 1H), 4.76 (t, J = 7.2 Hz,
2H), 3.29 (t, J = 7.2 Hz, 2H); 13C NMR (150 MHz, acetone) δ 156.1,
131.5, 129.2, 123.4, 120.5, 115.9, 75.4; HRMS (ESI-TOF) calcd for
C8H9NO3Na [M + Na]+ (190.0475), found 190.0481.
2-Methoxy-6-(2-nitro-1-phenylethyl)phenol (1s): Colorless
1
oil, 205 mg, 75% yield; H NMR (300 MHz, acetone) δ 7.83 (s,
1H), 7.46−7.39 (m, 2H), 7.35−7.27 (m, 2H), 7.26−7.19 (m, 1H),
6.91−6.84 (m, 2H), 6.81−6.75 (m, 1H), 5.35−5.21 (m, 3H), 3.83 (s,
3H); 13C NMR (126 MHz, acetone) δ 147.48, 143.92, 139.90, 128.48,
128.02, 126.96, 125.89, 120.00, 119.32, 110.18, 77.65, 55.44, 43.08;
HRMS (ESI-TOF) calcd for C15H15NO4Na [M + Na]+ (296.0893),
found 296.0895.
Preparation of Substrates 1p−1r. The Grignard reaction is the
same as above for the preparation of substrates 1a−1c, 1e−1o, and 1s.
Subsequent deprotection of the methyl group was processed as
previously described in ref 15.
4-(1-(2-Hydroxyphenyl)-2-nitroethyl)benzonitrile (1p): Col-
orless oil, 180 mg, two steps, yield 67%; 1H NMR (300 MHz, acetone)
δ 8.84 (s, 1H), 7.74 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 8.3 Hz, 2H), 7.30
(d, J = 7.7 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 6.92−6.82 (m, 2H),
5.40−5.31 (m, 3H); 13C NMR (150 MHz, acetone) δ 155.5, 146.5,
133.1, 129.2, 126.1, 120.9, 116.6, 111.6, 77.8, 44.3; HRMS (ESI-TOF)
calcd for C15H12N2O3Na [M + Na]+ (291.0740), found 291.0737.
2-(1-(4-Bromophenyl)-2-nitroethyl)phenol (1q): Colorless oil,
185 mg, two steps, yield 58%; 1H NMR (300 MHz, acetone) δ 8.77 (s,
1H), 7.50 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H), 7.25 (d, J = 7.7
Hz, 1H), 7.11 (td, J = 8.1, 1.5 Hz, 1H), 6.92−6.78 (m, 2H), 5.26 (s,
3H); 13C NMR (150 MHz, acetone) δ 155.4, 140.2, 132.3, 131.1,
129.3, 129.1, 126.6, 121.2, 120.8, 116.5, 78.2, 43.7; HRMS (ESI-TOF)
calcd for C14H12BrNO3Na [M + Na]+ (343.9893), found 343.9898.
2-(1-(4-Fluorophenyl)-2-nitroethyl)phenol (1r): Colorless oil,
175 mg, two steps, yield 67%; 1H NMR (300 MHz, acetone) δ 8.75 (s,
1H), 7.49−7.43 (m, 2H), 7.25 (d, J = 7.7 Hz, 1H), 7.14−7.04 (m,
3H), 6.89 (d, J = 7.8 Hz, 1H), 6.83 (t, J = 7.8 Hz, 1H), 5.29−5.24 (m,
3H); 13C NMR (150 MHz, acetone) δ 162.6 (d, J = 246.0 Hz), 155.4,
136.9, 130.8 (d, J = 8.1 Hz), 129.3, 129.1, 127.0, 120.7, 116.5, 116.4,
116.0 (d, J = 20.7 Hz), 78.6, 43.4; HRMS (ESI-TOF) calcd for
C14H12FNO3Na [M + Na]+ (284.0693), found 284.0685.
Preparation of Substrate 1t. Cmopound 1t was synthesized
following known procedure.18
2-(1-(1H-Indol-3-yl)-2-nitroethyl)phenol (1t): Colorless solid,
1
203 mg, 72% yield; H NMR (300 MHz, acetone) δ 10.21 (s, 1H),
8.85 (s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.41−7.36 (m, 2H), 7.18 (dd, J
= 7.6, 1.5 Hz, 1H), 7.12−7.03 (m, 2H), 7.02−6.88 (m, 2H), 6.74 (td, J
= 7.5, 1.1 Hz, 1H), 5.63 (t, J = 8.0 Hz, 1H), 5.20 (dd, J = 8.0, 1.4 Hz,
2H); 13C NMR (150 MHz, acetone) δ 155.5, 129.9, 128.9, 127.7,
127.2, 123.3, 122.5, 120.5, 119.7, 119.5, 116.3, 114.5, 112.2, 78.9, 36.0;
HRMS (ESI-TOF) calcd for C16H15N2O3 [M + H]+ (283.1077),
found 283.1085; mp 71−73 °C [lit.18 72−74 °C].
General Experimental Procedure for Construction of 3-
Alkyl-2-nitrobenzo[b]furans. The mixture of 2-(2-nitroethyl)-
phenol 1a (253 mg, 1.0 mmol), PhI(OAc)2 (966 mg, 3.0 mmol),
and Et3N (278 μL, 2.0 mmol) in CH3CN (10 mL) was treated with
Bu4NI (923 mg, 2.5 mmol). The reaction was allowed to stir at 35 °C
for 30 min. Upon completion as shown by TLC, the reaction mixture
was washed with saturated Na2S2O3 (20 mL) and extracted using ethyl
acetate (25 mL × 3). The organic layer was dried over MgSO4 and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (ethyl acetate/petroleum) to provide
corresponding 3-alkyl-2-nitrobenzo[b]furan 2a in 91% yield. Com-
pound 3a was obtained by the reaction above in the absence of Et3N
(Table 1, entry 2).
Preparation of Substrates 1i−1k.16 Magnesium powder (4.0
mmol) and nitroalkene (2.0 mmol) were placed and stirred at 0 °C.
The reaction was monitored by TLC. After the reaction was
completed, saturated NH4Cl (10 mL) was slowly poured into the
reaction mixture. The mixture was extracted with ethyl acetate (3 × 10
mL). The organic layer was separated, dried over MgSO4, and
evaporated under reduced pressure. The crude residue was subjected
to column chromatography (silica gel, ethyl acetate/petroleum) to
3-Butyl-7-methoxy-2-nitrobenzofuran (2a): Light yellow solid,
1
226 mg, 91% yield; H NMR (400 MHz, acetone) δ 7.46 (d, J = 7.9
Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 4.04 (s,
3H), 3.21−3.12 (t, J = 7.8 Hz, 2H), 1.78−1.67 (m, 2H), 1.50−1.39
(m, 2H), 0.95 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, acetone) δ
146.7, 142.0, 130.1, 126.4, 125.5, 115.0, 112.4, 56.6, 31.8, 24.7, 23.3,
7715
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The Journal of Organic Chemistry
Note
14.1; HRMS (ESI-TOF) calcd for C13H16NO4 [M + H]+ (250.1074),
found 250.1082; mp 100−101 °C.
Hz, 1H), 7.74−7.65 (m, 2H), 7.51−7.41 (m, 3H), 7.06 (t, J = 7.8 Hz,
2H), 4.63 (s, 2H); 13C NMR (150 MHz, acetone) δ 162.6 (d, J =
242.9 Hz), 152.5, 134.6, 131.4, 131.3 (d, J = 7.5 Hz), 128.2, 125.8,
124.1, 122.9, 116.1 (d, J = 21.0 Hz), 113.2; HRMS (ESI-TOF) calcd
for C15H11FNO3 [M + H]+ (272.0717), found 272.0723; mp 112−113
°C.
(2RS,3RS)-3-Butyl-7-methoxy-2-nitro-2,3-dihydrobenzofur-
an (3a): Colorless oil, 75 mg, 30% yield; 1H NMR (300 MHz,
acetone) δ 7.08−6.90 (m, 3H), 6.34 (d, J = 1.4 Hz, 1H), 3.91 (s, 3H),
3.78 (t, J = 7.1 Hz, 1H), 1.85−1.73 (m, 2H), 1.58−1.35 (m, 4H), 0.93
(t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, acetone) δ 146.8, 145.6,
130.0, 124.7, 117.3, 114.0, 111.3, 56.6, 51.5, 34.8, 29.1, 23.0, 14.1;
HRMS (ESI-TOF) calcd for C13H17NO4Na [M + Na]+ (274.1050),
found 274.1044.
3-(2-Chlorobenzyl)-7-methoxy-2-nitrobenzofuran (2k): Light
yellow solid, 269 mg, 85% yield; 1H NMR (300 MHz, acetone) δ 7.48
(d, J = 7.4 Hz, 1H), 7.34−7.20 (m, 5H), 7.10 (dd, J = 7.7, 1.0 Hz, 1H),
4.71 (s, 2H), 4.05 (s, 3H); 13C NMR (150 MHz, acetone) δ 146.8,
142.2, 135.9, 134.6, 131.2, 130.4, 129.8, 129.5, 128.2, 126.7, 121.6,
115.1, 112.4, 56.6, 28.9; HRMS (ESI-TOF) calcd for C16H13ClNO4
[M + H]+ (318.0528), found 318.0524; mp 129−130 °C.
7-Methoxy-3-(4-methylbenzyl)-2-nitrobenzofuran (2l): Light
3-Cyclohexyl-2-nitrobenzofuran (2b): Light yellow solid, 208
1
mg, 85% yield; H NMR (600 MHz, acetone) δ 8.06 (d, J = 7.8 Hz,
1H), 7.69−7.64 (m, 2H), 7.44 (td, J = 7.4, 1.2 Hz, 1H), 3.81 (tt, J =
12.0, 3.0 Hz, 1H), 2.01−1.98 (m,3H), 1.95−1.83 (m, 4H), 1.82−1.80
(m, 1H), 1.50−1.41 (m, 3H); 13C NMR (150 MHz, acetone) δ 152.6,
130.7, 128.5, 127.2, 125.6, 125.3, 113.3, 36.8, 31.9, 27.2, 26.4; HRMS
(ESI-TOF) calcd for C14H16NO3 [M + H]+ (246.1125), found
246.1126; mp 88−90 °C.
3-Butyl-2-nitrobenzofuran (2c): Light yellow solid, 195 mg, 89%
yield; 1H NMR (300 MHz, acetone) δ 7.95 (d, J = 8.1 Hz, 1H), 7.71−
7.63 (m, 2H), 7.45−7.50 (m, 1H), 3.20 (t, J = 7.5 Hz, 2H), 1.82−1.68
(m, 2H), 1.46 (dq, J = 14.8, 7.4 Hz, 2H), 0.95 (t, J = 7.3 Hz, 3H); 13C
NMR (150 MHz, acetone) δ 152.4, 131.2, 128.5, 125.6, 125.3, 123.8,
113.1, 31.8, 24.5, 23.3, 14.1; HRMS (ESI-TOF) calcd for C12H14NO3
[M + H]+ (220.0968), found 220.0964; mp 55−56 °C.
2-Nitrobenzofuran (2d): Light yellow solid, 148 mg, 91% yield;
1H NMR (300 MHz, acetone) δ 8.00−7.90 (m, 2H), 7.78−7.66 (m,
2H), 7.50 (t, J = 7.5 Hz, 1H); 13C NMR (150 MHz, acetone) δ 154.2,
130.9, 127.0, 126.2, 125.3, 113.3, 108.3; HRMS (ESI-TOF) calcd for
C8H6NO3 [M + H]+ (164.0342), found 164.0343; mp 132−133 °C
[lit.14 135 °C].
3-Isopropyl-7-methoxy-2-nitrobenzofuran (2e): Light yellow
solid, 207 mg, 88% yield; 1H NMR (300 MHz, acetone) δ 7.62 (d, J =
8.1 Hz, 1H), 7.37 (t, J = 8.1 Hz, 1H), 7.24 (d, J = 7.5 Hz, 1H), 4.16−
4.05 (m, 1H), 4.03 (s, 3H), 1.50 (d, J = 7.1 Hz, 6H); 13C NMR (150
MHz, acetone) δ 147.0, 142.3, 129.7, 128.5, 126.1, 116.5, 111.9, 56.5,
26.5, 21.4; HRMS (ESI-TOF) calcd for C12H14NO4 [M + H]+
(236.0917), found 236.0920; mp 76−77 °C.
1
yellow solid, 228 mg, 77% yield; H NMR (300 MHz, acetone) δ
7.35−7.34 (m, 2H), 7.28−7.20 (m, 3H), 7.10 (d, J = 7.8 Hz, 2H), 4.55
(s, 2H), 4.04 (s, 3H), 2.26 (s, 3H); 13C NMR (150 MHz, acetone) δ
146.7, 142.2, 137.0, 135.4, 130.1, 129.9, 129.4, 126.5, 123.6, 115.4,
112.4, 56.6, 30.3, 20.9; HRMS (ESI-TOF) calcd for C17H16NO4 [M +
H]+ (298.1074), found 298.1072; mp 148−149 °C.
3-Benzyl-7-methoxy-2-nitrobenzofuran (2m): Light yellow
1
solid, 235 mg, 83% yield; H NMR (300 MHz, acetone) δ 7.20−
6.94 (m, 7H), 4.33 (s, 2H), 3.77 (s, 3H); 13C NMR (150 MHz,
acetone) δ 146.7, 142.2, 138.5, 129.9, 129.51, 129.48, 127.6, 126.6,
123.3, 115.4, 112.4, 56.6, 30.7; HRMS (ESI-TOF) calcd for
C16H14NO4 [M + H]+ (284.0917), found 284.0920; mp 109−110 °C.
5-Chloro-3-(4-methylbenzyl)-2-nitrobenzofuran (2n): Light
1
yellow solid, 193 mg, 64% yield; H NMR (300 MHz, acetone) δ
7.82 (d, J = 1.4 Hz, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.67 (d, J = 9.0 Hz,
1H), 7.29 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 4.58 (s, 2H),
2.27 (s, 3H); 13C NMR (150 MHz, acetone) δ 150.9, 137.2, 135.1,
131.3, 130.9, 130.2, 129.8, 129.5, 123.5, 122.7, 115.0, 20.9; HRMS
(ESI-TOF) calcd for C16H13ClNO3 [M + H]+ (302.0578), found
302.0572; mp 129−130 °C.
5-Bromo-3-(4-methylbenzyl)-2-nitrobenzofuran (2o): Light
1
yellow solid, 290 mg, 84% yield; H NMR (300 MHz, acetone) δ
7.98 (d, J = 1.9 Hz, 1H), 7.81 (dd, J = 8.9, 1.8 Hz, 1H), 7.71 (d, J = 8.9
Hz, 1H), 7.29 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 4.58 (s,
2H), 2.27 (s, 3H); 13C NMR (150 MHz, acetone) δ 151.2, 137.2,
135.1, 134.0, 130.3, 130.2, 129.5, 126.7, 122.5, 118.2, 115.3, 30.1, 20.9;
HRMS (ESI-TOF) calcd for C16H13BrNO3 [M + H]+ (346.0073),
found 346.0076; mp 135−136 °C.
3-Cyclohexyl-7-methoxy-2-nitrobenzofuran (2f): Light yellow
solid, 234 mg, 85% yield; 1H NMR (300 MHz, acetone) δ 7.67 (d, J =
8.1 Hz, 1H), 7.36 (t, J = 8.1 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 4.03 (s,
3H), 3.82−3.75 (m, 1H), 2.04−1.80 (m, 8H), 1.52−1.44 (m, 2H); 13C
NMR (150 MHz, acetone) δ 147.0, 142.4, 128.79, 128.77, 126.1,
116.9, 111.9, 56.6, 36.91, 31.88, 27.3, 26.5; HRMS (ESI-TOF) calcd
for C15H18NO4 [M + H]+ (276.1230), found 276.1235; mp 75−77 °C.
5-Bromo-3-butyl-7-methoxy-2-nitrobenzofuran (2g): Light
4-(2-Nitrobenzofuran-3-yl)benzonitrile (2p): Light yellow
1
solid, 298 mg, 82% yield; H NMR (300 MHz, acetone) δ 8.03 (d,
J = 8.2 Hz, 2H), 7.96 (d, J = 8.3 Hz, 2H), 7.86−7.75 (m, 2H), 7.72 (d,
J = 8.1 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H); 13C NMR (150 MHz,
acetone) δ 152.5, 134.5, 133.2, 131.9, 131.5, 127.9, 126.6, 123.8, 121.0,
119.0, 113.8, 113.4; HRMS (ESI-TOF) calcd for C15H9N2O3 [M +
H]+ (265.0608), found 265.0612; mp 197−198 °C.
1
yellow solid, 304 mg, 93% yield; H NMR (300 MHz, acetone) δ
7.67 (s, 1H), 7.36 (s, 1H), 4.08 (s, 3H), 3.16 (t, J = 7.5 Hz, 1H), 1.78−
1.66 (m, 2H), 1.52−1.40 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H); 13C NMR
(150 MHz, acetone) δ 147.3, 140.9, 131.2, 124.7, 118.4, 117.5, 115.7,
57.2, 31.7, 24.6, 23.3, 14.1; HRMS (ESI-TOF) calcd for C13H15BrNO4
[M + H]+ (328.0179), found 328.0184; mp 74−75 °C.
3-(4-Bromophenyl)-2-nitrobenzofuran (2q): Light yellow solid,
1
247 mg, 78% yield; H NMR (300 MHz, acetone) δ 7.84−7.66 (m,
7H), 7.53 (dt, J = 7.0, 1.5 Hz, 1H); 13C NMR (150 MHz, acetone) δ
152.4, 132.8, 132.7, 132.6, 131.4, 128.7, 128.1, 126.4, 124.1, 124.0,
121.6, 113.3; HRMS (ESI-TOF) calcd for C14H9BrNO3 [M + H]+
(317.9760), found 317.9762; mp 140−141 °C.
3-Benzyl-2-nitrobenzofuran (2h): Light yellow solid, 195 mg,
1
77% yield; H NMR (300 MHz, acetone) δ 7.83 (d, J = 8.1 Hz, 1H),
7.74−7.64 (m, 2H), 7.47−7.38 (m, 3H), 7.33−7.18 (m, 3H), 4.64 (s,
2H); 13C NMR (150 MHz, acetone) δ 152.5, 138.5, 131.2, 129.55,
129.52, 125.5, 128.3, 127.6, 125.8, 124.2, 123.1, 113.2, 30.6; HRMS
(ESI-TOF) calcd for C15H12NO3 [M + H]+ (254.0812), found
254.0811; mp 104−105 °C.
3-(4-Fluorophenyl)-2-nitrobenzofuran (2r): Light yellow solid,
1
211 mg, 82% yield; H NMR (300 MHz, acetone) δ 7.83−7.70 (m,
5H), 7.53 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H); 13C NMR (150
MHz, acetone) δ 164.1 (d, J = 246.0 Hz), 152.4, 133.2 (d, J = 8.6 Hz),
131.4, 128.4, 126.3, 125.7, 124.1, 121.9, 116.4 (d, J = 20.7 Hz), 113.3;
HRMS (ESI-TOF) calcd for C14H9FNO3 [M + H]+ (258.0561),
found 258.0559; mp 167−168 °C.
3-(2-Fluorobenzyl)-2-nitrobenzofuran (2i): Light yellow solid,
1
241 mg, 89% yield; H NMR (300 MHz, acetone) δ 7.79−7.66 (m,
3H), 7.44 (t, J = 7.0 Hz, 1H), 7.39−7.27 (m, 2H), 7.18−7.07 (m, 2H).
4.65 (s, 2H); 13C NMR (150 MHz, acetone) δ 161.8 (d, J = 244.0
Hz), 152.5, 131.6 (d, J = 3.6 Hz), 131.3, 129.8 (d, J = 7.4 Hz), 128.2,
125.8, 125.4 (d, J = 3.8 Hz), 125.3 (d, J = 14.7 Hz), 123.9, 121.7, 116.1
(d, J = 22.0 Hz), 113.2, 24.0 (d, J= 5.0 Hz); HRMS (ESI-TOF) calcd
for C15H11FNO3 [M + H]+ (272.0717), found 272.0724; mp 107−108
°C.
7-Methoxy-2-nitro-3-phenylbenzofuran (2s): Light yellow
1
solid, 234 mg, 87% yield; H NMR (300 MHz, acetone) δ 7.71 (dd,
J = 7.8, 1.7 Hz, 2H), 7.63−7.54 (m, 3H), 7.42 (t, J = 8.0 Hz, 1H), 7.31
(d, J = 7.3 Hz, 1H), 7.22 (dd, J = 8.0, 0.9 Hz, 1H), 4.09 (s, 3H); 13C
NMR (125 MHz, acetone) δ 146.8, 142.1, 130.8, 130.2, 130.0, 129.6,
129.4, 127.0, 123.0, 115.3, 112.5, 56.7; HRMS (ESI-TOF) calcd for
C15H12NO4 [M + H]+ (270.0761), found 270.0759; mp 156−157 °C.
3-(4-Fluorobenzyl)-2-nitrobenzofuran (2j): Light yellow solid,
1
198 mg, 73% yield; H NMR (300 MHz, acetone) δ 7.84 (d, J = 8.0
7716
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The Journal of Organic Chemistry
Note
3-(2-Nitrobenzofuran-3-yl)-1H-indole (2t): Red solid, 200 mg,
72% yield; 1H NMR (300 MHz, acetone) δ 11.04 (s, 1H), 8.06 (d, J =
2.7 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.83−7.69 (m, 2H), 7.61 (d, J =
8.2 Hz, 1H), 7.52−7.43 (m, 2H), 7.26 (td, J = 7.6, 0.9 Hz, 1H), 7.14
(td, J = 7.4, 0.9 Hz, 1H); 13C NMR (150 MHz, acetone) δ 152.7,
137.6, 131.2, 129.5, 128.5, 126.9, 125.6, 125.2, 123.2, 121.4, 121.0,
118.4, 113.2, 113.1, 104.0; HRMS (ESI-TOF) calcd for C16H11N2O3
[M + H]+ (279.0764), found 279.0773; mp 177−178 °C.
(8) For reviews, see: (a) Wirth, T. Angew. Chem., Int. Ed. 2005, 44,
3656. (b) Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem. 2008, 4229.
(c) Merritt, E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052.
(d) Pouysegu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66,
2235. (e) Duschek, A.; Kirsch, S. F. Angew.Chem., Int. Ed. 2011, 50,
1524. (f) Merritt, E. A.; Olofsson, B. Synthesis 2011, 517.
(9) For reviews, see: (a) Moriarty, R. M.; Prakash, O. Adv. Heterocycl.
Chem. 1998, 69, 1. (b) Koser, G. F. Adv. Heterocycl. Chem. 2004, 86,
225. (c) Silva, L. F., Jr. Molecules 2006, 11, 421.
(10) (a) Yamaguchi, M.; Shiraishi, T.; Hirama, M. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1176. (b) Yamaguchi, M.; Shiraishi, T.; Hirama, M.
J. Org. Chem. 1996, 61, 3520. (c) Halland, N.; Abured, P. S.;
Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42, 661.
(11) (a) Tohma, H.; Takizawa, S.; Watanabe, H.; Kita, Y. Tetrahedron
Lett. 1998, 39, 4547. (b) Tohma, H.; Takizawa, S.; Maegawa, T.; Kita,
Y. Angew. Chem., Int. Ed. 2000, 39, 1306. (c) Tohma, H.; Maegawa, T.;
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(12) (a) Fan, R. H.; Sun, Y.; Ye, Y. Org. Lett. 2009, 11, 5174. (b) Sun,
Y.; Fan, R. H. Chem. Commun. 2010, 46, 6834.
(13) (a) Chen, L.; Shi, E.; Liu, Z.; Chen, S.; Wei, W.; Li, H.; Xu, K.;
Wan, X. Chem.Eur. J. 2011, 17, 4085. (b) Uyanik, M.; Suzuki, D.;
Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed. 2011, 50, 5331.
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9-Isopropyl-5-(2-morpholinoethoxy)-8-nitro-4-propyl-2H-
furo[2,3-h]chromen-2-one (2u): Light yellow solid, 297 mg, two
1
steps, 67% yield; H NMR (500 MHz, acetone) δ 7.28 (s, 1H), 6.23
(s, 1H), 4.45−4.37 (m, 3H), 3.64 (t, J = 4.0 Hz, 4H), 3.14 (t, J = 7.5
Hz, 2H), 2.93 (t, J = 7.5 Hz, 2H), 2.56 (t, J = 4.0 Hz, 4H), 1.77−1.69
(m, 2H), 1.53 (d, J = 7.0 Hz, 6H), 1.04 (t, J = 7.5 Hz, 3H); 13C NMR
(125 MHz, acetone) δ 160.8, 159.4, 158.9, 155.1, 152.6, 131.1, 113.7,
110.3, 108.6, 92.7, 67.9, 67.4, 57.8, 54.6, 39.5, 25.5, 23.7, 20.4, 14.2;
HRMS (ESI-TOF) calcd for C23H29N2O7 [M + H]+ (445.1969),
found 445.1966; mp 158−160 °C.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gangliu27@tsinghua.edu.cn.
■
(14) Tromelin, A.; Demerseman, P.; Royer, R. Synthesis 1985, 11,
1074.
(15) Peschko, C.; Winklhofer, C.; Terpin, A.; Steglich, W. Synthesis
2006, 18, 3048.
(16) Shi, W.; Wang, J. X. Synthesis 2009, 4, 597.
(17) Dauzonne, D.; Royer, R. Synthesis 1984, 12, 1054.
(18) Habib, P. M.; Kavala, V.; Kuo, C. W.; Yao, C. F. Tetrahedron
Lett. 2008, 49, 7005.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The research is financially supported by the National Natural
Science Foundation of China (No. 81161120402) and National
863 Program of China (No. 2012AA020303).
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