A practical indium tribromide catalysed addition of indoles to nitroalkenes in aqueous media

Article abstract of DOI:10.1055/s-2002-31970

The 1,4-conjugate addition of indoles to nitroalkenes was efficiently carried out in aqueous media using a catalytic amount of indium tribromide (5 mol%). The reusability of the indium tribromide was tested by performing consecutive cycles with the same c

Full text of DOI:10.1055/s-2002-31970

1
110
PAPER
A Practical Indium Tribromide Catalysed Addition of Indoles to Nitroalkenes
in Aqueous Media
A
M
P
ractica
l
Indium Tri
a
bromide
C
a
r
talyse
d
cd dition of
o
Indoles to
N
itroalk
B
e
nes in
A
queous
a
Media ndini,* Paolo Melchiorre, Alfonso Melloni, Achille Umani-Ronchi*
Dipartimento di Chimica ‘G. Ciamician’, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy
Fax +39(51)2099456; E-mail: bandini@ciam.unibo.it, umani@ciam.unibo.it
Received 27 March 2002; revised 9 April 2002
During our ongoing studies on the conjugate addition of
indoles to , –unsaturated ketones catalysed by indium
Abstract: The 1,4-conjugate addition of indoles to nitroalkenes
was efficiently carried out in aqueous media using a catalytic
amount of indium tribromide (5 mol%). The reusability of the indi-
7
tribromide, we found that InBr (1 mol%) smoothly pro-
3
um tribromide was tested by performing consecutive cycles with the moted the addition of 2-methylindole (5a) to trans- -ni-
same catalyst.
trostyrene (6a) in CH Cl affording the desired 2-phenyl-
2 2
2
-[3 -(2-methylindolyl)]nitroethane (7aa) in 93% isolated
Key words: alkaloids, catalysis, indium, indoles, Michael addi-
tions
8
yield after 16 h. However, due to the well known toler-
ance of indium salts towards aqueous conditions and con-
sidering the higher reactivity of nitroalkenes in
comparison to other Michael acceptors, we tested the ef-
fectiveness of the catalytic protocol in aqueous media.
Thus, we started an investigation of Michael additions be-
tween nitro-olefin 6a and variously substituted indoles
In recent years, catalytic Michael-type additions of nu-
cleophiles to nitroalkenes have emerged as a powerful
method for the formation of new carbon–carbon bonds in
1
organic synthesis. In particular, the use of electron-rich
catalysed by InBr in H O–THF (9:1) as the solvent lead-
ing to a library of -nitroindoles 7 (Table 1).
hetero-aromatic compounds such as indoles, acting as nu-
cleophiles, allows the synthesis of 2-indolyl-1-nitroal-
3
2
kanes 1, highly versatile intermediates for the preparation It is noteworthy that while in the absence of InBr the re-
3
of several classes of biological active compounds such as action afforded the desired product only in 28% yield after
2
melatonin analogs 2, 1,2,3,4-tetrahydro- -carbolines 48 h (Table 1, entry 1), the use of 5 mol% of anhyd InBr3
3
4
(
THBCs) 3 and ‘triptans’ 4 (Scheme).
furnished a complete conversion (Table 1, entry 2) after 2
h. The protocol was significantly effective for the addi-
tion of several substituted electron-rich indoles such as N-
methyl-2-methylindole (5c) and 5-methoxyindole (5e)
that furnished the products in excellent yields: 92 and
9
Since pioneering papers published by Noland et al. on the
addition of indolylmagnesium iodide to nitro-olefins,5
many efforts have been devoted to the development of6
Friedel–Crafts type addition of indoles to nitroalkenes.
8
8%, respectively (Table 1, entries 4 and 6). Under the re-
However, the tendency of electron-rich hetero-aromatic
rings to polymerize under acid-catalysed conditions
makes these processes still challenging.
ported conditions, even indolyl rings bearing electron-
withdrawing groups such as the 5-bromoindole (5d) are
R
NHCOR''
R'
N
H
2
R
NO2
R'
R
NO2
R'
R'
+
R
NH
N
H
N
1
N
H
H
3
R
NH2
R'
N
H
4
Scheme Synthetic versatility of indolylnitroalkane derivatives.
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
1
©
437-210X,E;2002,0,08,1110,1114,ftx,en;Z05302SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
A Practical Indium Tribromide Catalysed Addition of Indoles to Nitroalkenes in Aqueous Media
1111
Table 2 InBr Catalysed Addition of Indoles to Nitroalkenesa
Table 1 InBr Catalysed Addition of Indoles to trans- -Nitrosty-
rene (6a)
3
3
a
R1
R3
Ph
InBr3 (5 mol%)
NO2
R3
NO2
NO2
InBr3
+
R1
R2
NO2
R2 + Ph
N
THF / H O
R2
2
H2O / THF
R2
H
6
N
N
R1
5
7
N
R1
H
5
6a
7
1
2
1
2
6
a: R =Ph, R =H;
6c: R =2-thiophenyl, R =H;
1
2
1
2
6b: R =R =-(CH2)4-; 6d: R =2-furanyl, R =H;
1
2
3
1
2
3
5
5
5
5
a: R =H, R =Me, R =H;
5e: R =H, R =H, R =OMe;
1
2
3
1
2
3
b: R =H, R =H, R =H;
5f: R =Me, R =H, R =H;
Yield (%)b
1
2
3
1
2
3
Entry
1
Indole
Nitroalkene Product
c: R =Me, R =Me, R =H; 5g: R =H, R =Ph, R =H
1
2
3
d: R =H, R =H, R =Br;
5a
6b
7ab
44
(66:34)c
Yield (%)b
28c
Entry
Indole
5a
Time (h)
Product
7aa
2
3
4
5
6
5a
5a
5b
5c
5c
5e
6c
6d
6d
6c
6d
6d
7ac
7ad
7bd
7cc
7cd
7ed
95
99
92
99
91
65
1
2
3
4
5
6
7
24
2
5a
7aa
93
60
92
65
88
98
75
5b
5c
16
2
7ba
7ca
5d
5e
3
7da
7ea
7
2
a
All the reactions were carried out with 5 mol% of catalyst at r.t. and
quenched after 2 h reaction time.
5f
16
16
7fa
b
Isolated yield after flash chromatography.
8
5g
7ga
c
1
The diastereoisomeric ratio was determined by H NMR on the
a
All the reactions were carried out with 5 mol% of catalyst at r.t. un-
less otherwise indicated.
Isolated products after flash chromatography.
crude product.
b
c
Without InBr . A significant amount of byproduct derived from in-
3
dole polymerization was observed.
Table 3 Consecutive Michael Additions Promoted by the Same
Amount (10 mol%) of InBr3
Run
1
2
3
3
12
92
4
16
91
5
24
91
suitable nucleophiles for the Michael addition affording
the 1,4-adduct 7da in satisfactory yield (65%, entry 5).
Time (h)
Yield (%)
0.5
Having optimized a convenient protocol for the conjugate
addition of indoles to 6a, we became interested in explor-
ing this process with several nitroalkenes (6a,d). The re-
sults are collected in Table 2.
93
93
runs the compound 7aa was isolated in almost quantita-
The Michael additions proceeded cleanly and, in particu-
lar, commercially available trans-2-(2-nitrovinyl)thio-
phene (6c) and 2-(2-nitrovinyl)furan (6d) afforded a clear
reaction mixture and the products were isolated in excel-
lent yields (up to 99%). However, when 1-nitro-1-cyclo-
hexene (6b) was reacted with 5a, the desired 7ab was
obtained only in moderate yield and diastereoselectivity
tive yields.
At the end of the reactions, the pH of the aqueous phase
was measured to be about 3.5, probably due to a partial
acidic hydrolysis of the indium salt in water. However, the
possibility that the Brønsted acid formed in situ could be
the real promoter of the Michael reaction was denied by a
comparative experiment carried out between 6a and 5a in
an acidic solution (pH 3, by HBr 10–3 M). Under these
conditions, the reaction, monitored by TLC, was signifi-
cantly slower (10 h for a complete conversion) and a ten-
tative experiment of reusability failed.
(
44%, 66:34, entry 1, Table 2). This result proves the
higher reactivity of -aryl- -nitroalkenes with respect to
simple , -unsaturated nitro derivatives in our catalytic
protocol.
A typical request for the design of environmentally friend-
ly catalytic processes is the recovery and reusability of the
catalyst. Thus, we tested this possibility simply by carry-
ing out consecutive Michael addition reactions between
In summary, with the present study we described a general
and mild InBr catalysed protocol for the conjugate addi-
3
tion of indoles to nitroalkenes. The reactions are easily
performed and remarkably tolerant of substituents at dif-
ferent positions of the indolyl rings. The simple process
performed in aqueous media provides the access to highly
functionalised compounds in excellent yields and allows
5
a and 6a (InBr 10 mol%) with the same catalyst loading
3
(
Table 3). The experiment was easily performed by a care-
ful separation of the organic compounds (extraction with
CH Cl ) from the aqueous phase after each run. The reus-
2
2
ability of the catalyst was remarkable, in fact after five
Synthesis 2002, No. 8, 1110–1114 ISSN 0039-7881 © Thieme Stuttgart · New York

1
112
M. Bandini et al.
PAPER
the reusability of the catalyst for several times without 1H NMR (300 MHz, CDCl
loss of effectiveness.
): = 4.92 (dd, J = 7.8, 20.4 Hz, 1 H),
.00–5.07 (m, 1 H), 5.11–5.16 (m, 1 H), 7.07 (d, J = 2.1 Hz, 1 H),
.20–7.38 (m, 6 H), 7.55 (d, J = 1.8 Hz, 1 H), 8.16 (br, 1 H).
3
5
7
1
3
C NMR (75 MHz, CDCl ): = 41.23, 79.35, 100.14, 112.85,
1H NMR spectra were recorded by means of Varian Gemini-200
3
1
1
13.15, 113.87, 121.36, 122.72, 125.55, 127.60, 127.71, 128.99,
35.02, 138.65.
(200 MHz) or Varian INOVA-300 (300 MHz) spectrometers.
Chemical shifts are given in with respect to TMS and coupling
constants J are measured in Hz. Data are reported as follows: chem-
ical shifts, multiplicity (s = singlet, d = doublet, t = triplet,
Anal. Calcd for (C H BrN O ): C, 55.67; H, 3.80; N, 8.12. Found:
C, 55.62; H, 4.64; N, 8.11.
16 13
2
2
1
3
q = quartet, br = broad, m = multiplet). C NMR spectra were re-
corded on a Varian Gemini-200 (50 MHz) or Varian INOVA-300
7
ea
Yield: 88%; pale yellow viscous oil; flash chromatography (cyclo-
hexane–Et O, 85:15), R 0.33.
(
75 MHz) spectrometers with complete proton decoupling. Chemi-
cal shifts are reported in ppm from tetramethylsilane with the sol-
vent as the internal standard (deuterochloroform: = 77.0). Column
flash chromatographies were run over 270–400 mesh silica gel.
2
f
IR (neat): 3351, 2942, 2850, 1558, 1481, 1370, 1213 cm–1.
1
H NMR (200 MHz, CDCl ): = 3.79 (s, 3 H), 4.90–5.04 (m, 2 H),
.10–5.22 (m, 1 H), 6.85–6.89 (m, 1 H), 6.98 (d, J = 2.2 Hz, 1 H),
.30–7.36 (m, 6 H), 8.19 (br, 1 H).
3
3
Commercially available anhyd InBr , indoles and nitroalkenes were
3
5
7
purchased from the Aldrich and Co. and used as received. Elemen-
tal analyses were carried out by using a EACE 1110 CHNOS ana-
lyzer. IR analysis were performed with a FT-IR NICOLET 205
spectrophotometer. IR spectra of neat compounds are expressed by
1
C NMR (50 MHz, CDCl ): = 35.64, 55.85, 77.77, 100.41,
3
107.26, 110.39, 111.05, 112.20, 112.60, 123.25, 126.01, 131.27,
142.11, 152.04, 154.08.
–1
wavenumber (cm ). The melting points were uncorrected. The
compound 7ba has been previously described.8
Anal. Calcd for (C H N O ): C, 68.91; H, 5.44; N, 9.45. Found: C,
1
7
16
2
3
6
8.85; H, 5.40; N, 9.44.
Catalytic Michael addition; Typical Procedure
To a round-bottomed flask were added solvent (H O–THF, 9:1; 2
2
7
fa
mL), anhyd InBr (5 mg, 0.015 mmol) and nitrostyrene (0.3 mmol).
3
Yield: 98%; pale yellow viscous oil; flash chromatography (cyclo-
hexane–Et O, 9:1), R 0.30.
After 10 min stirring, to the resulting pale-yellow solution, indole
2
f
(
0.45 mmol) was added. The reaction was stirred at r.t. until com-
plete consumption of the nitro compound (checked by TLC) and
then extracted with Et O (3 5 mL). The organic phases were col-
–
1
IR (neat): 3058, 3028, 2914, 1549, 1474, 1376, 1333, 741, 701 cm .
2
1H NMR (300 MHz, CDCl3): = 3.75 (s, 3 H), 4.95 (ddd, J = 1.2,
9.6, 12.3 Hz, 1 H), 5.05 (ddd, J = 1.2, 7.8, 12.3 Hz, 1 H), 5.19 (t,
J = 5.7 Hz, 1 H), 7.05–7.10 (m, 1 H), 7.20–7.34 (m, 8 H), 7.45 (dd,
J = 0.9, 7.8 Hz, 1 H).
lected, dried (Na SO ) and concentrated under reduced pressure.
2
4
The crude product was finally purified by flash chromatography.
7
aa
Yield: 93%; pale pink solid; mp 98–101 °C; flash chromatography
cyclohexane–Et O, 85:15), R 0.30.
1
3
C NMR (50 MHz, CDCl ): = 26.88, 32.69, 41.44, 79.40, 109.38,
3
1
1
12.60, 118.80, 119.27, 122.04, 126.19, 127.32, 127.56, 128.71,
37.11, 139.23.
(
2
f
–
1
IR (Nujol): 3393, 3031, 2923, 2853, 1551, 1460, 1378 cm .
Anal. Calcd for (C H N O ): C, 72.84; H, 5.75; N, 9.99. Found: C,
1
7
16
2
2
1
H NMR (200 MHz, CDCl ): = 2.40 (s, 3 H), 5.08–5.13 (m, 1 H),
3
72.80; H, 5.70; N, 9.98.
5
.17–5.29 (m, 2 H), 6.98–7.18 (m, 3 H), 7.25–7.42 (m, 6 H), 7.89
(
1
br, 1 H).
7
ga
Yield: 75%; yellow solid; mp 111–114 °C; flash chromatography
cyclohexane–Et O, 9:1), R 0.33.
3
C NMR (50 MHz, CDCl ): = 11.97, 40.44, 78.56, 108.68,
3
(
1
1
10.62, 118.47, 119.60, 121.20, 126.71, 126.96, 127.18, 128.65,
32.77, 135.26, 139.37.
2
f
IR (Nujol): 3404, 2923, 2852, 1547, 1458, 1376 cm–1.
Anal. Calcd for (C H N O ): C, 72.84; H, 5.75, N, 9.99. Found: C,
1
1
7
16
2
2
H NMR (200 MHz, CDCl ): = 5.15–5.21 (m, 2 H), 5.27–5.38 (m,
H), 7.09–7.20 (m, 1 H), 7.24–7.56 (m, 13 H), 8.18 (br, 1 H).
3
7
2.78; H, 5.70; N, 9.97.
1
1
3
C NMR (50 MHz, CDCl ): = 40.79, 79.01, 109.41, 111.35,
3
7
ca
1
1
19.83, 120.16, 122.34, 125.04, 127.06, 127.34, 128.48, 128.67,
28.76, 128.81, 132.03, 135.93, 136.84, 139.75. Anal. Calcd for
Yield: 92%; orange solid; mp 135–139 °C; flash chromatography
cyclohexane–Et O, 85:15), R =0.27.
(
2
f
(
C H N O ): C, 77.17; H, 5.30; N, 8.18. Found: C, 77.14; H, 5.26;
22 18 2 2
–
1
IR (Nujol): 3312, 2925, 2853, 1547, 1463, 1376, 743 cm .
N, 8.16.
1
H NMR (200 MHz, CDCl ): = 2.42 (s, 3 H), 3.67 (s, 3 H), 5.10–
3
7
ab
5
.25 (m, 3 H), 6.98–7.10 (m, 1 H), 7.12–7.21 (m, 1 H), 7.26–7.40
Yield: 44%; pale yellow solid; dr 66:34; flash chromatography (cy-
clohexane–Et O, 9:1), R 0.25.
(
m, 7 H).
13C NMR (75 MHz, CDCl3): = 10.33, 29.45, 40.63, 78.63, 108.07,
1
1
2
f
–
1
IR (Nujol): 3398, 2923, 2853, 1539, 1459, 1376 cm .
09.00, 118.52, 119.25, 120.76, 125.86, 127.19, 128.63, 134.55,
36.86, 139.75.
1
H NMR (300 MHz, CDCl ): (major diastereoisomer) = 1.45–1.58
3
(
m, 2 H), 1.63–1.80 (m, 1 H), 1.88–2.10 (m, 4 H), 2.42 (s, 3 H),
Anal. Calcd for (C H N O ): C, 73.45; H, 6.16; N, 9.52. Found: C,
18
18
2
2
2
2
1
5
.84–2.94 (m, 1 H), 3.33 (dt, J = 4.2, 13.5 Hz, 1 H), 7.04–7.13 (m,
H), 7.25 (d, J = 7.2 Hz, 1 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.77 (br,
H); (minor diastereoisomer) 2.36 (s, 3 H), 3.34–3.43 (m, 1 H),
.09 (dt, J = 4.2, 11.1 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H).
7
3.42; H, 6.12; N, 9.50.
7
da
Yield: 65%; pale yellow solid; mp 116–120 °C; flash chromatogra-
phy (cyclohexane–Et O, 75:25), R 0.30.
2
f
13C NMR (50 MHz, CDCl3): (major diastereoisomer) = 13.21,
20.16, 25.32, 26.38, 30.34, 39.42, 85.92, 110.28, 117.82, 119.31,
–
1
IR (Nujol): 3429, 2930, 2853, 1548, 1459, 1376 cm .
Synthesis 2002, No. 8, 1110–1114 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Practical Indium Tribromide Catalysed Addition of Indoles to Nitroalkenes in Aqueous Media
1113
1
1
20.99, 123.39, 126.47, 131.93, 134.71; (minor diastereoisomer)
1.74, 24.61, 25.67, 32.50, 89.16, 119.16, 120.79, 127.92, 129.06.
Anal. Calcd for (C H N O S): C, 63.98; H, 5.37; N, 9.39. Found:
C, 63.91; H, 5.33; N, 9.33.
1
6
16
2
2
Anal. Calcd for (C H N O ): C, 69.74; H, 7.02; N, 10.84. Found:
C, 69.72; H, 6.97; N, 10.84.
15
18
2
2
7
cd
Yield: 91%; pale yellow solid; mp 115–118 °C; flash chromatogra-
phy (cyclohexane–Et O, 85:15), R 0.30.
2
f
7
ac
Yield: 95%; yellow solid; mp 95–98 °C; flash chromatography (cy-
clohexane–Et O, 9:1), R 0.31.
IR (Nujol): 3121, 2923, 2852, 1559, 1504, 1472, 1411, 1380, 1170,
1012, 911 cm .
–
1
2
f
–
1
1
IR (Nujol): 3415, 2923, 2853, 1549, 1458, 1377, 712 cm .
H NMR (200 MHz, CDCl ): = 2.42 (s, 3 H), 3.67 (s, 3 H), 4.90–
3
1
4.99 (m, 1 H), 5.16–5.27 (m, 2 H) 6.09 (d, J = 3.4 Hz, 1 H), 6.29
H NMR (200 MHz, CDCl ): = 2.41 (s, 3 H), 5.12–5.25 (m, 2 H),
.38–5.43 (m, 1 H), 6.95–6.97 (m, 2 H), 7.06–7.29 (m, 4 H), 7.40
d, J = 7.0 Hz, 1 H), 7.98 (br, 1 H).
3
(
dd, J = 1.8, 3.2 Hz), 7.08 (dt, J = 1.2, 6.6 Hz, 1 H), 7.16 (dt,
5
(
J = 1.2, 6.6 Hz, 1 H), 7.26–7.30 (m, 1 H), 7.37–7.41 (m, 2 H).
13C NMR (50 MHz, CDCl
): = 10.29, 29.52, 35.50, 77.00, 105.45,
06.98, 108.92, 110.26, 118.36, 119.15, 120.79, 125.49, 134.70,
36.70, 141.70, 152.28.
1
3
3
C NMR (75 MHz, CDCl ): = 11.74, 35.49, 78.85, 108.51,
3
1
1
1
1
10.71, 118.57, 119.67, 121.38, 124.42, 124.68, 126.30, 126.77,
32.99, 135.35, 143.31.
Anal. Calcd for (C H N O ): C, 67.59; H, 5.67; N, 9.85. Found: C,
1
6
16
2
3
Anal. Calcd for (C H N O S): C, 62.92; H, 4.93; N, 9.78. Found:
C, 62.85; H, 4.89; N, 9.77.
1
5
14
2
2
6
7.55; H, 5.63; N, 9.84.
7
ed
7
ad
Yield: 65%; yellow solid; mp 115–118 °C; flash chromatography
cyclohexane–Et O, 85:15), R 0.28.
Yield: 99%; yellow viscous oil; flash chromatography (cyclohex-
ane–Et O, 9:1), R 0.30.
(
2
f
2
f
IR (Nujol) 3322, 2923, 2852, 1552, 1489, 1463, 1377, 1213, 742
cm .
IR (neat): 3414, 2921, 1706, 1549, 1459, 1428, 1301, 1227, 1015,
–
1
–1
7
34, 646 cm .
1H NMR (200 MHz, CDCl3): = 2.41 (s, 3 H), 4.96 (dd, J = 10.6,
.6 Hz, 1 H), 5.16–5.25 (m, 2 H), 6.09–6.11 (m, 1 H), 6.31 (dd,
J = 2.0, 3.4 Hz, 1 H), 7.06–7.15 (m, 2 H), 7.27–7.29 (m, 1 H), 7.38–
1H NMR (200 MHz, CDCl
): = 3.84 (s, 3 H), 4.91–4.95 (m, 1 H),
3
5
6
.00–5.10 (m, 1 H), 5.18–5.25 (m, 1 H), 6.15–6.18 (m, 1 H), 6.28–
.32 (m, 1 H), 6.86–6.91 (m, 1 H), 6.95–6.98 (m, 1 H), 7.10–7.12
3
(
m, 1 H), 7.26–7.29 (m, 1 H), 7.39 (s, 1 H), 8.05 (br, H).
13C NMR (75 MHz, CDCl
): = 35.65, 55.89, 77.82, 100.62,
07.33, 110.46, 111.35, 112.22, 112.77, 123.31, 126.18, 131.42,
42.22, 152.21, 154.34.
7
.42 (m, 2 H), 7.95 (br, 1 H).
1
3
3
C NMR (50 MHz, CDCl ): = 11.88, 35.51, 77.18, 106.38,
3
1
1
1
1
07.36, 110.60, 110.88, 118.60, 119.77, 121.47, 126.64, 133.39,
35.48, 142.06, 152.35.
Anal. Calcd for (C H N O ): C, 62.93; H, 4.93; N, 9.79. Found: C,
1
5
14
2
4
Anal. Calcd for (C H N O ): C, 66.66; H, 5.22; N, 10.36. Found:
C, 66.61; H, 5.18; N, 10.34.
15
14
2
3
6
2.88; H, 4.89; N, 9.78.
7
bd
Acknowledgements
Yield: 92%; brown–yellow oil; flash chromatography (cyclohex-
ane–Et O, 95:5), R 0.31.
2
f
We would like to thank M.U.R.S.T. (Progetto Nazionale ‘Stereose-
lezione in Sintesi Organica: Metodologie ed Applicazioni’) and Bo-
logna University (funds for selected research topics) for the
financial support of this research.
IR (neat): 3559, 3419, 3119, 3058, 2696, 2923, 1552, 1457, 1423,
1
–
1
378 cm .
1
H NMR (300 MHz, CDCl ): = 4.93 (dd, J = 4.8, 8.2 Hz, 1 H),
3
5
.07 (dd, J = 5.2, 8.2 Hz, 1 H), 5.27 (dd, J = 4.8, 5.2 Hz, 1 H), 6.18
(
7
dd, J = 0.9, 2.2 Hz, 1 H), 6.33 (dd, J = 1.8, J = 3.3 Hz, 1 H), 7.12– References
.18 (m, 1 H), 7.24–7.27 (m, 3 H), 7.39–7.40 (m, 1 H), 7.59 (dd,
(
1) (a) For recent reviews see: Leonard, J. Contemp. Org. Synth.
994, 1, 387. (b) Rossiter, B. E.; Swingle, N. M. Chem. Rev.
J = 1.2, 8.1 Hz, 1 H), 8.16 (br, 1 H).
1
1
3
C NMR (75 MHz, CDCl ): = 35.68, 77.84, 107.31, 110.42,
3
1992, 92, 771.
2) Fînaru, A.; Berthault, A.; Besson, T.; Guillaumet, G.;
Berteina-Raboin, S. Tetrahedron Lett. 2002, 43, 787.
1
1
11.52, 118.62, 119.98, 122.56, 122.69, 125.65, 136.28, 142.18,
52.20.
(
Anal. Calcd for (C H N O ): C, 65.62; H, 4.72; N, 10.93. Found:
(3) (a) Zhu, H. J.; Zhao, B. T.; Zuo, G. Y.; Pittman, C. U. Jr.;
14
12
2
3
C, 66.58; H, 4.68, N, 10.92.
Dai, W. M.; Hao, X. J. Tetrahedron: Asymmetry 2001, 12,
2613. (b) Paulvannan, K.; Hale, R.; Mesis, R.; Chen, T.
7
cc
Tetrahedron Lett. 2002, 43, 203.
Yield: 99%; pale green solid; mp: 111–113 °C; flash chromatog-
raphy (cyclohexane–Et O, 9:1), R 0.25.
(4) (a) Yevich, J. P.; Yocca, F. D. Curr. Med. Chem. 1997, 4,
295. (b) Jand, K. S.; Barrett, V.; Brockwell, M.; Cambridge,
D.; Farrant, D. R.; Foster, C.; Giles, H.; Glen, R. C.; Hill, A.
P.; Hobbs, H.; Honey, A.; Martin, G. R.; Salmon, J.; Smith,
D.; Woollard, P.; Selwood, D. L. J. Med. Chem. 2001, 44,
2
f
–
1
IR (Nujol): 3101, 3046, 2922, 2854, 1545, 1471, 1375, 1335 cm .
1
H NMR (200 MHz, CDCl ): = 2.42 (s, 3 H), 3.67 (s, 3 H), 5.03–
3
5
7
7
.28 (m, 2 H), 5.40 (dd, J = 6.6, 8.8 Hz, 1 H), 6.91–6.95 (m, 2 H),
.00–7.13 (m, 1 H), 7.16–7.20 (m, 2 H), 7.28 (d, J = 8.0 Hz, 1 H),
.37 (d, J = 7.2 Hz, 1 H).
6
81.
(5) (a) Noland, W. E.; Hartman, P. J. J. Chem. Soc. 1954, 76,
227. (b) Noland, W. E.; Christensen, G. M.; Sauer, G. L.;
3
13C NMR (50 MHz, CDCl3): = 10.26, 29.47, 35.52, 77.00, 105.52,
Dutton, G. G. S. J. Chem. Soc. 1955, 77, 456.
6) (a) Chakrabarty, M.; Basak, R.; Ghosh, N. Tetrahedron Lett.
(
1
1
06.95, 108.89, 110.24, 118.35, 119.01, 120.79, 125.52, 135.63,
36.72, 141.49, 152.31.
2
2
001, 41, 3913. (b) Komoto, I.; Kobayashi, S. Org. Lett.
002, 4, in press.
Synthesis 2002, No. 8, 1110–1114 ISSN 0039-7881 © Thieme Stuttgart · New York

1
114
M. Bandini et al.
PAPER
(
7) Bandini, M.; Cozzi, P. G.; Giacomini, M.; Melchiorre, P.;
Selva, S.; Umani-Ronchi, A. J. Org. Chem. 2002, 67, in
press.
described, see: Yadav, J. S.; Abraham, S.; Reddy, B. V. S.;
Sabitha, G. Synthesis 2001, 2165. Under our conditions,
InCl was found less effective in comparison to InBr in the
3
3
(
8) Recently, Yadav et. al. reported that InCl (10 mol%) was
addition of 5a to 6a, 82% yield.
3
also able to promote the conjugate addition of indole 5b to
(9) Other common Lewis acids were found to be less effective
in term of chemical yields and reaction times (i.e. AlCl3,
68% yield, 24 h).
6
a in 78% yield using CH Cl as the solvent. However, only
2 2
one example of conjugate addition to nitroalkenes was
Synthesis 2002, No. 8, 1110–1114 ISSN 0039-7881 © Thieme Stuttgart · New York