I2-catalyzed Michael addition of indole and pyrrole to nitroolefins

Article abstract of DOI:10.1016/j.tet.2005.09.038

An easy and efficient method to generate indolyl nitroalkane 5 and pyrrolyl nitroalkane 7 in high yields using β-nitrostyrene and indole/pyrrole at room temperature in the presence of catalytic amount of iodine is reported. The short reaction times and hi

Full text of DOI:10.1016/j.tet.2005.09.038

Tetrahedron 61 (2005) 11751–11757
I2-catalyzed Michael addition of indole and pyrrole to nitroolefins
Chunchi Lin, Jianming Hsu, M. N. V. Sastry, Hulin Fang,
*
Zhijay Tu, Ju-Tsung Liu and Yao Ching-Fa
Department of Chemistry, National Taiwan Normal University 88, Sec. 4, Tingchow Road, Taipei, 116 Taiwan, ROC
Received 15 August 2005; revised 8 September 2005; accepted 9 September 2005
Available online 14 October 2005
Abstract—An easy and efficient method to generate indolyl nitroalkane 5 and pyrrolyl nitroalkane 7 in high yields using b-nitrostyrene and
indole/pyrrole at room temperature in the presence of catalytic amount of iodine is reported. The short reaction times and high yields of
product are noteworthy. Molecular iodine promoted Michael addition is operationally simple and efficient method compared to the known
Lewis acids or rare earth metal catalysts to generate different indolyl/pyrrolyl nitroalkanes in high yield.
q 2005 Published by Elsevier Ltd.
1. Introduction
products of indole and pyrrole derivatives involves
troublesome isolation procedures to obtain the desired
product with some of the Lewis acids. Furthermore, many
procedures require longer reaction times, expensive and
toxic reagents in stoichiometric amounts, air sensitive
conditions, difficult workup procedures.
Indole and many of its derivatives are most important units
in many naturally occurring compounds, because of a wide
variety of their pharmacological and biological properties.1
The hapalindole alkaloids, which exhibit significant
antibacterial and antimycotic activity, and several indole
alkaloids such as uleine, aspidospermidine, ibophyllidine
alkaloids, and numerous tryptamine derivatives are also
associated with important biological activity.2 Likewise,
important pyrrole derivatives also present in compounds
such as bile pigments, vitamin B12, haemin, chlorophyll,
and related natural products.3 In addition, several pyrrole
derivatives are important intermediates not only for the
synthesis of drugs, pigments and pharmaceuticals but also
for the development of organic functional groups.4 There-
fore, development of new synthetic methods of indole and
pyrrole derivatives have been widely studied using various
Lewis acids as well as Bronsted acids.5 Since the 3-position
of the indole is the ideal site for electrophilic attack,
3-substituted indoles are versatile intermediates for the
synthesis of a wide variety of indole derivatives. Con-
versely, C-2 position of pyrrole is indeed the electron-rich
site for Michael addition. Michael addition of indoles and
pyrroles to various nucleophiles has been well documented
in the literature using either protic or Lewis acids.6–9
However, Lewis acid-catalyzed Michael addition of indole
and pyrrole necessitate careful control over the acidity to
avoid the undesirable side reactions such as dimerization
and polymerization.10 Incidentally, the polymerized
The use of molecular iodine in organic synthesis has been
known for a long time. In recent years molecular iodine has
received considerable attention as an inexpensive, nontoxic,
readily available catalyst for various organic transform-
ations under mild and convenient conditions to afford the
corresponding products in excellent yields with high
selectivity.11 Another advantage in using iodine as catalyst,
will not influence the nitro group, which is very significant
for b-nitrostyrene 3. Herein, some important pharmaceutical
compounds, tryptamine 1 and serotonin 2, which can be
obtained as a result of Michael addition between indole and
nitroalkene (Fig. 1). Especially serotonin, a simple
derivative of indole is a major neurotransmitter and
many indole derivatives also mimic the binding of
neurotransmitter to its receptors also have been syn-
thesized.12 In continuation of our work in exploring the
methods using b-nitrostyrene, we had the opportunity to
focus on the iodine catalyzed Michael addition of
Keywords: b-Nitrostyrene; Indole; Pyrrole; Iodine; Michael addition.
*
Corresponding author. Tel.: C886 2 29309092; fax: C886 2 29324249;
e-mail: cheyaocf@scc.ntnu.edu.tw
Figure 1.
0040–4020/$ - see front matter q 2005 Published by Elsevier Ltd.
doi:10.1016/j.tet.2005.09.038

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C. Lin et al. / Tetrahedron 61 (2005) 11751–11757
Table 1. Iodine catalyzed Michael addition between nitroolefins and indole
b-nitrostyrene 3 with indole, because the resultant products
are analogs of 1 and 2 after reducing the nitro group (Fig. 1).
Serial no.
Entrya
Time (h)
Productb
Yield (%)c
1
2
3
4
5
3a
3b
3c
3d
3e
2
5a
5b
5c
5d
5e
99
99
99
89
94
In this paper, we wish to report that elemental iodine can be
used as a mild and efficient catalyst for the Michael addition
of b-nitrostyrene 3 with indole 4 and pyrrole 6 at room
temperature to afford products 2-indolyl-2-phenyl-1-
nitroalkane 5 and 2-pyrrolyl-2-phenyl-1-nitroalkane 7 in
high to excellent yields.
2.5
18
2
6
a All reactions were performed at 1 mmol scale using 30 mol% of iodine in
0.5 mL of ether.
b All products were well characterized by 1H NMR, 13C NMR, and mass
spectroscopy.
c NMR yields of the crude products.
2. Results and discussion
(Table 1). Although all Michael adducts were obtained in
excellent yields, but the reaction times varied according to
the nature of the substitution pattern on the phenyl ring. The
electron donating groups substituted in the phenyl ring of
the nitrostyrene led to the formation of products with longer
reaction times. The heterocyclic nitroolefins (3d–3e) also
afforded the adducts in high yield. The lower yield of 5d
over 5e can be explained on the basis of the product
stability.
In the beginning, Michael reaction between indole and
b-nitrostyrene 3 was carried out using iodine (30 mol%) in
chloroform (0.5 mL) led to the formation of 2-indolyl-2-
phenyl-1-nitroalkane 5 in 95% yield. With this encouraging
result, next we investigated the fate of reaction in different
solvents. Conducting the reaction in DMSO did not proceed
and DMF as a solvent afforded only 10% of the product with
several unwanted side products. After substantial experi-
mentation with different solvents (CH2Cl2, 82% yield;
CHCl3, 95% yield; EtOAc, 91% yield), diethylether came
out as a solvent of choice. The iodine catalyzed reaction in
ether not only improved the product yields, but also reduced
the reaction times. We next, investigated the amount of
iodine required to catalyze the transformation. As less as
10 mol% of iodine afforded the products in 43% yield, after
18 h. By means of 20 mol% of iodine though product yields
were improved to 72%, but the reaction time is almost same
as that of 10 mol%. On the other hand, using 30 mol% of
iodine as a catalyst afforded the products in 99% yield in 2 h
(Scheme 1).
In order to extend the scope of this methodology, pyrrole 6
was subjected as a nucleophile in Michael addition with
differnet b-nitrostyrenes, to generate 2-pyrrolyl-2-phenyl-1-
nitroalkanes 7a–e in good yields (Scheme 2).
To check the versatility of iodine catalyzed Michael
reaction, various substituted b-nitrostyrenes (3a–c) were
reacted with indole 4 using iodine (30 mol%) in ether
(0.5 mL) solution and the results were summarized
Scheme 2.
The reasons for the lower product yields in case of pyrrole,
when compared to indole may be ascribed due to
polymerization of products in some cases. This is due to
high nucleophilicity of pyrroles, which facilitates to react
rapidly than indole. Using molecular iodine in catalytic
amount to generate 2-alkyl pyrroles in excellent yields is
noteworthy (Table 2).
Table 2. Iodine catalyzed Michael addition between nitroolefins and
pyrrole
Serial no.
Entrya
Time (h)
Productb
Yield (%)c
1
2
3
4
5
3a
3b
3c
3d
3e
1
1
1.5
1.3
1.2
7a
7b
7c
7d
7e
86
76
79
85
81
a All reactions were performed at 1 mmol scale using 30 mol% of iodine in
0.5 mL of ether.
b All products were well characterized by 1H NMR, 13C NMR, and mass
spectroscopy.
c NMR yields of the crude products.
So as to utilize this extensively effective protocol, we
examined by taking various other indole and pyrrole
derivatives with b-nitrostyrene 3. N-methylpyrrole 8
Scheme 1.

C. Lin et al. / Tetrahedron 61 (2005) 11751–11757
11753
Table 3. Iodine catalyzed Michael addition of b-nitrostyrene with methyl substituted indole or pyrrole
Serial no.
Entry (indole/pyrrole)a
Time
Productb
Yield (%)c
1
45 min
99
99
9
8
2
20 min
10
11
3
4
20 min
99
70
12
14
13
15
2 days
a All reactions were performed at 1 mmol scale using 30 mol% of iodine in 0.5 mL of ether.
b All products were well characterized by 1H NMR, 13C NMR, and mass spectroscopy.
c NMR yields of the crude products.
and methyl substituted indoles such as N-methylindole 10,
2-methylindole 12, and 3-methylindole 14 afforded the
products in good to excellent yields under similar reaction
conditions (Table 3). Besides, we have not observed any
byproducts, which are iodated either on indole or pyrrole
nucleus. The substituted derivatives of both indole and
pyrrole gave the products in excellent yield during less time,
when compared to their unsubstituted counterparts. A
possible explanation may be due to the presence of the
methyl group, which not only increases the electron density
of the aromatic ring to accelerate the reaction, but also
prevents the unwanted side reactions such as polymer-
ization. In case of 3-methylindole 14, which undergoes
conjugate addition at the 2-position may involve more
complicated mechanism. It has been reported in the
literature, that the mechanism involving addition at
2-position proceeds through the initial attack of the
electrophile at C-3, followed by a 1,2-shift in the
intermediate cation leads to the formation of final product.3
The longer reaction times and lower product yields in
the addition of b-nitrostyrene to 3-methylindole clearly
supports the above proposed mechanism.
In addition to this, we have also examined the fate of a
different nitroolefin like 2-(4-chlorophenyl)-3-nitro-2H-
chromene 16, since the resultant 2H-benzopyran derivatives
such as flavonols13 and amines14 belongs to medicinally
important compounds. In our previous report, we have
provided an easy and efficient method to prepare 16 using
DABCO in catalytic amount.15 Using 50 mol% of iodine,
2-(4-chlorophenyl)-3-nitro-2H-chromene in a reaction with
indole gave 73% of 17 and 26% of 18 in ether solution at
room temperature after 2.5 days (Scheme 3). The two
stereoisomers were separated through column chromato-
graphy and the ratio was determined by the crude NMR
analysis. In addition to this, the two stereoisomers were also
characterized by the single X-ray crystallography (Figs. 2
and 3) and suggested a trans configuration between the aryl
substituent at 2-position and the indolyl group at 4-position
for the compound 17. The formation of major product as
Scheme 3.

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C. Lin et al. / Tetrahedron 61 (2005) 11751–11757
clearly indicates the steric hindrance of the nitroolefin plays a
significant role in determining the reaction time. Moreover,
the product 20 is an important intermediate and can be
reduced to tryptamine 1, a neurotransmitter.17a–b
3. Conclusions
In summary, we have achieved a simple, efficient, and
practical Michael addition process for the synthesis of
various 2-indolyl-2-aryl-1-nitroalkanes 5 and 2-pyrrolyl-2-
aryl-1-nitroalkanes 7 from b-nitrostyrene using catalytic
amount of iodine. The significant advantage of this catalytic
reaction lies in its usage under mild and ambient conditions.
The yields are generally excellent (up to 98%) without any
byproducts and the reaction times are also short. Further
investigations are in progress on the application of this
methodology to the synthesis of natural product molecules
with indole or pyrrole moiety and other heterocyclic ring
systems.
Figure 2. X-ray crystal structure of 17.
4. Experimental
4.1. General
All reactions were performed in room temperature and all
chemicals including solvent used for reactions without
drying. Analytical thin-layer chromatography was per-
formed with E. Merck silica gel 60F glass plates and flash
chromatography by use of E. Merck silica gel 60 (230–400
mesh). MS or HRMS were measured by JEOL JMS-D300 or
JEOL JMS-HX110 spectrometer. 1H and 13C NMR spectra
were recorded with Bruker Aavance EX 400.
4.2. Material
b-Nitrostyrene 1, indole, pyrrole, and iodine were purchased
from Aldrich Chemical Co. and other commercially
available reagents were used without further purification.
2-(4-Chlorophenyl)-3-nitro-2H-chromene 16, nitroethylene
19 were prepared according to the literature procedures and
spectral data was consistent with the literature report.
Figure 3. X-ray crystal structure of 18.
trans isomer can be explained on the basis of steric
hindrance in which the two bulky groups are trans to each
other separated by a nitro group.
4.3. Typical experimental procedure for the synthesis of
adducts 5 or 7 (a: ArZPh, b: ArZ4-ClC6H4, c: ArZ4-
MeOC6H4, d: ArZthienyl, e: ArZfuryl)
In order to apply the remarkable catalytic activity of iodine,
for the synthesis of biologically important compound, a less
hindered nitroolefin like nitroethylene 1916 was used as
Michael acceptor. Using 10 mol% of iodine, nitroethylene 19
reacts readily with indole at 0 8C, to afford the product 2017 in
98% yield (Scheme 4). The formation of 2-indolyl-1-
nitroethane 20 in less than 5 min, and the formation of
2-(4-chlorophenyl)-4-indolyl-3-nitrochroman 17 in 2.5 days,
Indole 4 (4.0 mmol) or pyrrole 6 (4.0 mmol) was added to a
suspension of b-nitrostyrene 3 (1.0 mmol) in diethyl ether
(0.5 mL) along with iodine (0.3 mmol) at room temperature
for several minutes to hours. After completion the reaction
(monitored by TLC), it was quenched with water and
washed with (2!10 mL) aq Na2S2O3 and extracted into
CH2Cl2 (3!20 mL). The combined organic phases were
washed sequentially with brine and water and dried over
anhyd Na2SO4. Evaporation of the organic solvent afforded
the crude products 5a–e or 7a–e.
4.3.1. 2-Phenyl-2-indolyl-1-nitroethane (5a). 1H NMR
(400 MHz, CDCl3) d 7.93 (s, 1H), 7.40 (d, JZ8.00 Hz, 1H),
7.27–7.10 (m, 8H), 6.82 (d, JZ2.36 Hz, 1H), 5.12 (dd, JZ
8.36, 7.68 Hz, 1H), 4.95 (dd, JZ12.52, 7.68 Hz, 1H), 4.84
Scheme 4.

C. Lin et al. / Tetrahedron 61 (2005) 11751–11757
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(dd, JZ12.52, 8.36 Hz, 1H). 13C NMR (100 MHz, CDCl3) d
139.13, 136.26, 128.72, 127.58, 127.36, 125.88, 122.38,
121.56, 119.67, 118.66, 113.86, 111.37, 79.33, 41.35. MS
m/z (relative intensity) 266 (MC, 8), 219 (100), 204 (44),
178 (19), 115 (11), 108 (17). HRMS calcd for C16H14N2O2
(MC) 266.1055, found 266.1051.
169 (100), 156 (40), 154 (39), 77 (12). HRMS calcd for
C12H12N2O2 (MC) 216.0899, found 216.0900.
4.3.7. 2-(4-Chlorophenyl)-2-pyrrolyl-1-nitroethane (7b).
1H NMR (400 MHz, CDCl3) d 7.88 (s, 1H), 7.30 (d, JZ
8.40 Hz, 2H), 7.15 (d, JZ8.40 Hz, 2H), 6.69–6.67 (m, 1H),
6.16 (dd, JZ5.76, 2.76 Hz, 1H), 6.07–6.05 (m, 1H), 4.94
(dd, JZ12.12, 7.12 Hz, 1H), 4.84 (dd, JZ7.88, 7.12 Hz,
1H), 4.75 (dd, JZ12.12, 7.88 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 136.53, 133.99, 129.32, 129.22,
128.28, 118.43, 108.72, 105.95, 78.94, 42.27.
4.3.2. 2-(4-Chlorophenyl)-2-indolyl-1-nitroethane (5b).
1H NMR (400 MHz, CDCl3) d 8.09 (s, 1H), 7.39 (d, JZ
7.96 Hz, 1H), 7.33 (d, JZ8.20 Hz, 1H), 7.29–7.07 (m, 6H),
6.98 (s, 1H), 5.14 (dd, JZ8.56, 7.40 Hz, 1H), 5.02 (dd, JZ
12.52, 7.40 Hz, 1H), 4.88 (dd, JZ12.52, 8.56 Hz, 1H). 13C
NMR (100 MHz, CDCl3) d 137.64, 136.25, 133.04, 128.96,
128.83, 125.67, 122.55, 121.46, 119.80, 118.55, 113.38,
111.43, 79.03, 40.70. MS m/z (relative intensity) 300 (MC,
33), 254 (41), 253 (100), 240 (64), 218 (37), 115 (14), 108
(25). HRMS calcd for C16H13ClN2O2 (MC) 300.0666,
found 300.0671.
4.3.8. 2-(4-Methoxylphenyl)-2-pyrrolyl-1-nitroethane
(7c). H NMR (400 MHz, CDCl3) d 7.85 (s, 1H), 7.14–
1
7.11 (m, 2H), 6.88–6.84 (m, 2H), 6.67–6.65 (dd, JZ5.96,
2.76 Hz, 1H), 6.16–6.14 (m, 1H), 6.06–6.04 (m, 1H), 4.94
(dd, JZ11.92, 6.96 Hz, 1H), 4.82 (dd, JZ8.04, 6.96 Hz,
1H), 4.74 (dd, JZ11.92, 8.04 Hz, 1H), 3.78 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 159.30, 129.84, 129.24, 128.98,
118.03, 114.53, 108.58, 105.54, 79.37, 55.26, 42.18. MS m/z
(relative intensity) 246 (MC, 13), 199 (100), 186 (66), 171
(14), 168 (20), 77 (9). HRMS calcd for C13H14N2O3 (MC)
246.1004, found 246.1006.
4.3.3. 2-(4-Methoxylphenyl)-2-indolyl-1-nitroethane
(5c). H NMR (400 MHz, CDCl3) d 8.09 (s, 1H), 7.43 (d,
1
JZ7.92 Hz, 1H), 7.36–7.16 (m, 4H), 7.09–7.00 (m, 2H),
6.87–6.23 (m, 2H), 5.13 (dd, JZ8.44, 7.48 Hz, 1H), 5.03
(dd, JZ12.24, 7.48 Hz, 1H), 4.89 (dd, JZ12.24, 8.44 Hz,
1H), 3.77 (s, 3H). 13C NMR (100 MHz, CDCl3) d 158.95,
136.57, 131.24, 128.84, 126.15, 122.72, 121.47, 119.97,
119.03, 114.86, 114.33, 111.38, 79.79, 55.28, 40.90. MS m/z
(relative intensity) 296 (MC, 38), 250 (32), 249 (88), 236
(100), 218 (20), 115 (12). HRMS calcd for C17H16N2O3
(MC) 296.1161, found 296.1161.
1
4.3.9. 2-Thienyl-2-pyrrolyl-1-nitroethane (7d). H NMR
(400 MHz, CDCl3) d 8.03 (s, 1H), 7.25–7.23 (m, 1H), 6.93–
6.92 (m, 2H), 6.68–6.70 (m, 1H), 6.18–6.15 (m, 1H), 6.11–
6.09 (m, 1H), 5.19 (dd, JZ7.96, 7.52 Hz, 1H), 4.92 (dd, JZ
12.88, 7.52 Hz, 1H), 4.82 (dd, JZ12.88, 7.96 Hz, 1H). 13C
NMR (100 MHz, CDCl3) d 140.99, 128.29, 127.17, 125.86,
125.55, 118.25, 108.81, 105.92, 79.66, 38.19. MS m/z
(relative intensity) 222 (MC, 1), 206 (2), 168 (11), 88 (37),
73 (40), 79 (78), 61 (100). HRMS calcd for C10H10N2OS
(MCK16) 206.0463, found 206.0540.
4.3.4. 2-Thienyl-2-indolyl-1-nitroethane (5d). 1H NMR
(400 MHz, CDCl3) d 8.12 (s, 1H), 7.52–7.50 (m, 1H), 7.38–
7.36 (m, 1H), 7.24–7.09 (m, 4H), 6.99–6.93 (m, 2H), 5.44
(dd, JZ8.16, 7.56 Hz, 1H), 5.05 (dd, JZ12.48, 7.56 Hz,
1H), 4.98 (dd, JZ12.48, 8.16 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 142.85, 136.16, 126.81, 125.48,
125.08, 124.73, 122.45, 121.94, 119.79, 118.57, 113.49,
111.49, 79.78, 36.70. MS m/z (relative intensity) 272 (MC,
33), 226 (26), 225 (100), 212 (74), 210 (20), 167 (9), 115
(15). HRMS calcd for C14H12N2O2S (MC) 272.0619, found
272.0620.
4.3.10. 2-Furyl-2-pyrrolyl-1-nitroethane(7e). 1H NMR
(400 MHz, CDCl3) d 8.26 (s, 1H), 7.39–7.38 (m, 1H),
6.72–6.60 (m, 1H), 6.33–6.31 (m, 1H), 6.18–6.13 (m, 2H),
6.09–6.07 (m, 1H), 5.00 (dd, JZ7.76, 7.56 Hz, 1H), 4.88
(dd, JZ12.76, 7.76 Hz, 1H), 4.79 (dd, JZ12.64, 7.56 Hz,
1H). 13C NMR (100 MHz, CDCl3) d 150.71, 142.70,
126.19, 118.27, 110.56, 108.79, 107.76, 106.65, 77.74,
36.94. MS m/z (relative intensity) 206 (MC, 10), 159 (100),
158 (9), 146 (52), 80 (6). HRMS calcd for C10H10N2O3
(MC) 206.0691, found 206.0687.
4.3.5. 2-Furyl-2-indolyl-1-nitroethane (5e). 1H NMR
(400 MHz, CDCl3) d 7.81 (s, 1H), 7.44 (d, JZ7.92 Hz,
1H), 7.21–7.00 (m, 4H), 6.73–6.71 (m, 1H), 6.15–6.13 (m,
1H), 6.01–5.99 (m, 1H), 5.12 (dd, JZ8.20, 7.40 Hz, 1H),
4.85 (dd, JZ12.56, 8.20 Hz, 1H), 4.69 (dd, JZ12.56,
7.40 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 152.03,
141.96, 135.98, 125.37, 122.68, 122.20, 119.66, 118.34,
111.48, 110.80, 110.25, 107.03, 77.57, 35.39. MS m/z
(relative intensity) 256 (MC, 32), 210 (22), 209 (100), 196
(84), 167 (23), 117 (16), 115 (12). HRMS calcd for
C14H12N2O3 (MC) 256.0848, found 256.0846.
4.4. Typical experimental procedure for the synthesis of
adducts 9, 11, 13 and 15
Methyl substituted indole 10, 12, 14 (4.0 mmol) or methyl
substituted pyrrole 8 (4.0 mmol) was added to a suspension
of b-nitrostyrene 3 (1.0 mmol) in diethyl ether (0.5 mL)
along with iodine (0.3 mmol) at room temperature for
several minutes to hours. After completion the reaction
(monitored by TLC), it was quenched with water and
washed with (2!10 mL) aq Na2S2O3 and extracted into
CH2Cl2 (3!20 mL). The combined organic phases were
washed sequentially with brine and water and dried over
anhyd Na2SO4. Evaporation of the organic solvent afforded
the crude products 9, 11, 13, 15.
1
4.3.6. 2-Phenyl-2-pyrrolyl-1-nitroethane (7a). H NMR
(400 MHz, CDCl3) d 7.83 (s, 1H), 7.35–7.19 (m, 5H), 6.40
(dd, JZ4.04, 2.60 Hz, 1H), 6.14 (dd, JZ6.04, 2.84 Hz, 1H),
6.05–6.07 (m, 1H), 4.94 (dd, JZ11.88, 7.28 Hz, 1H), 4.86
(dd, JZ7.52, 7.28 Hz, 1H), 4.76 (dd, JZ11.88, 7.52 Hz,
1H). 13C NMR (100 MHz, CDCl3) d 137.95, 129.13,
128.85, 128.04, 127.83, 118.14, 108.57, 105.73, 79.12,
42.84. MS m/z (relative intensity) 216 (MC, 10), 170 (22),
4.4.1. 2-(N-methylpyrroyl)-2-phenyl-1-nitroethane (9).
1H NMR (400 MHz, CDCl3) d 7.20–7.07 (m, 5H), 6.43

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C. Lin et al. / Tetrahedron 61 (2005) 11751–11757
(s, 1H), 6.04–6.01 (m, 2H), 4.80–4.72 (m, 2H), 4.60–4.52
(m, 1H), 3.05 (s, 3H). 13C NMR (100 MHz, CDCl3) d
137.82, 129.00, 128.59, 127.53, 127.30, 122.47, 106.45,
105.42, 78.79, 41.18, 33.06. MS m/z (relative intensity) 230
(MC, 41), 184 (40), 183 (66), 170 (100), 128 (17), 96 (35),
77 (13). HRMS calcd for C12H12N2O2 (MC) 230.1055,
found 230.1053.
123.21, 122.03, 120.66, 119.85, 118.04, 117.66, 117.02,
111.84, 87.20, 72.01, 37.05. MS m/z (relative intensity) 406
(MCC2, 8), 404 (MC, 23), 359 (18), 358 (22), 357 (53),
243 (100), 241 (30), 220 (44), 130 (18). HRMS calcd for
C23H17ClN2O3 (MC) 404.0928, found 404.0928. Anal.
Calcd for C23H17ClN2O3: C, 68.23; H, 4.23; N, 6.92. Found:
C, 68.99; H, 5.02; N, 6.97.
4.4.2. 2-(N-methylindolyl)-2-phenyl-1-nitroethane (11).
1H NMR (400 MHz, CDCl3) d 7.39–6.93 (m, 9H), 6.67 (s,
1H), 5.06 (dd, JZ8.72, 7.92 Hz, 1H), 4.83 (dd, JZ12.32,
7.92 Hz, 1H), 4.76 (dd, JZ12.32, 8.72 Hz, 1H), 3.14 (s,
3H). 13C NMR (100 MHz, CDCl3) d 139.31, 136.99,
128.59, 127.49, 127.19, 126.32, 126.07, 121.89, 119.15,
118.71, 112.43, 109.33, 79.19, 41.23, 32.24. MS m/z
(relative intensity) 280 (MC, 44), 234 (50), 233 (74), 220
(100), 217 (17), 146 (17), 115 (13). HRMS calcd for
C17H16N2O2 (MC) 280.1212, found 280.1213.
4.5.2. (2R,3S,4S)-2-(4-chlorophenyl)-4-indolyl-3-nitro-
chroman (18). 1H NMR (400 MHz, CDCl3) d 8.17 (s,
1H), 7.39–6.93 (m, 12H), 6.88 (d, JZ2.56 Hz, 1H), 5.54 (d,
JZ9.32 Hz, 1H), 5.37 (dd, JZ9.32, 5.56 Hz, 1H), 5.16 (d,
JZ5.56 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 153.06,
136.07, 135.22, 135.03, 130.26, 129.24, 128.96, 126.93,
124.79, 122.67, 121.96, 121.64, 120.37, 118.20, 116.70,
113.43, 111.48, 87.20, 73.51, 37.90. MS m/z (relative
intensity) 406 (MCC2, 14), 404 (MC, 45), 359 (13), 358
(17), 357 (36), 243 (27), 241 (89), 220 (100), 132 (37).
HRMS calcd for C23H17ClN2O3 (MC) 404.0928, found
404.0932. Anal. Calcd for C23H17ClN2O3: C, 68.23; H,
4.23; N, 6.92. Found: C, 68.54; H, 3.98; N, 6.80.
4.4.3. 2-(2-Methylindolyl)-2-phenyl-1-nitroethane (13).
1H NMR (400 MHz, CDCl3) d 7.92 (s, 1H), 7.62 (d, JZ
7.8 Hz, 1H), 7.50–7.25 (m, 8H), 5.40–5.28 (m, 2H), 5.23
(dd, JZ11.76, 8.84 Hz, 1H), 2.35 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 139.30, 135.11, 132.85, 128.46,
127.00, 126.76, 126.51, 120.87, 119.33, 118.21, 110.65,
108.22, 78.24, 40.21, 11.28. MS m/z (relative intensity) 280
(MC, 62), 234 (49), 220 (100), 146 (49), 115 (8), 77 (8).
HRMS calcd for C17H16N2O2 (MC) 280.1212, found
280.1218.
4.6. Typical experimental procedure for the synthesis of
adduct 20
Indole 4 (2.0 mmol) was added to a suspension of
nitroethylene 19 (1.0 mmol) in diethyl ether (0.5 mL)
along with iodine (0.1 mmol) at 0 8C less than 5 min. The
reaction was monitored by TLC. After completion the
reaction mixture was quenched and washed with (2!
10 mL) aqueous Na2S2O3 solution and extracted with
CH2Cl2 (3!20 mL). The combined organic phases were
washed sequentially with brine and water and dried
(Na2SO4). The solvent was removed to obtain the crude
product 20.
4.4.4. 2-(3-Methylpyrroyl)-2-phenyl-1-nitroethane (15).
1H NMR (400 MHz, CDCl3) d 7.62 (s, 1H), 7.52 (d, JZ
7.68 Hz, 1H), 7.41–7.08 (m, 8H), 5.25 (dd, JZ8.28,
7.64 Hz, 1H), 5.08 (dd, JZ12.88, 8.28 Hz, 1H), 4.95 (dd,
JZ12.88, 7.64 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 137.00, 135.66, 130.55, 129.23, 128.98, 127.88,
127.16, 122.16, 119.49, 118.56, 110.75, 109.25, 77.41,
40.96, 8.51. MS m/z (relative intensity) 280 (MC, 45), 234
(72), 233 (69), 218 (100), 217 (80), 204 (42), 146 (52), 128
(40), 105 (45), 77 (68). HRMS calcd for C17H16N2O2 (MC)
280.1212, found 280.1212.
4.6.1. 2-Indolyl-1-nitroethane 20. 1H NMR (400 MHz,
CDCl3) d 8.87 (s, 1H), 7.47–6.75 (m, 4H), 6.75 (s, 1H), 4.47
(t, JZ7.12 Hz, 2H), 3.31 (t, JZ7.08 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 135.92, 126.36, 122.57, 122.08,
119.47, 117.86, 111.34, 109.40, 75.50, 23.22.
4.5. Typical experimental procedure for the synthesis of
adducts 17 and 18
Acknowledgements
Indole 4 (4.0 mmol) was added to a suspension of 2-(4-
chlorophenyl)-3-nitro-2H-chromene 16 (1.0 mmol) in
diethyl ether (1.0 mL) along with iodine (0.5 mmol) at
room temperature for several minutes to hours. The reaction
was monitored by TLC. After completion the reaction
mixture was quenched and washed with (2!10 mL)
aqueous Na2S2O3 solution and extracted with CH2Cl2
(3!20 mL). The combined organic phases were washed
sequentially with brine and water and dried (Na2SO4). The
solvent was removed to obtain the crude product 17 and 18.
Financial support by the National Science Council of the
Republic of China and National Taiwan Normal University
(ORD93-C) is gratefully acknowledged.
References and notes
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