Synthesis of a new series of 2-vinylindoles and their cycloaddition reactivity

Article abstract of DOI:10.1016/j.tet.2010.02.080

The regioselective synthesis of 2-vinylindoles was achieved through the use of 4,7-dihydroindole 19. Reactions of these 2-vinylindoles as 4π-component gave 2,3-disubstitue indoles as well as the expected Diels-Alder products.

Full text of DOI:10.1016/j.tet.2010.02.080

Tetrahedron 66 (2010) 2936–2939
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Synthesis of a new series of 2-vinylindoles and their cycloaddition reactivity
,
Tayfun Arslan a, Ali Enis Sadak b, Nurullah Saracoglu b
*
a Department of Chemistry, Faculty of Arts and Sciences, Giresun University, Giresun 28049, Turkey
b Department of Chemistry, Faculty of Sciences, Atatu¨rk University, Erzurum 25240, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
The regioselective synthesis of 2-vinylindoles was achieved through the use of 4,7-dihydroindole 19.
Received 1 December 2009
Received in revised form 22 January 2010
Accepted 22 February 2010
Available online 25 February 2010
Reactions of these 2-vinylindoles as 4
Diels–Alder products.
p
-component gave 2,3-disubstitue indoles as well as the expected
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Ph
N
O
O
n(CH2)
O
O
n(CH2)
The vinylindole skeleton appears to be an attractive substrate as
diene component in Diels–Alder reactions. For instance, the cy-
cloaddition of vinylindoles with carbon- and heteroatomic dien-
ophiles provides indole alkaloids, carbazoles, [b]annelated indole
derivatives.1–19 Prudhomme et al. synthesized structural analogs of
granulatimide (1) and investigated their biological activities as new
checkpoint kinase 1 inhibitors (Fig. 1).20 Some of the corresponding
syntheses, such as cycloadducts 2 and 3, were carried out through
Diels–Alder reactions of N-Boc-vinylindoles 4 and 5.
O
N
N
N
N
HN
10
Ph
N
N
H
6-9
H
11-14
O
n=1,2,3,4
n=1,2,3,4
Scheme 1.
O
N
H
H
15-18
n(CH )
H
O
N
O
N
O
O
n=1,2,3,4
O
Figure 2. Structures of targeted 2-vinylindoles 15–18.
NH
O
N
N
N
(CH )n
N
H
Boc
(CH )n
H
Although there are numerous methods to prepare 3-substitue
indoles, a limited number of methods have been reported for access to
2-substituted indoles. An indirect method for the synthesis of 2-acyl-
indoles from 4,7-dihydroindole 19 was improved by Joule et al.22
Recently, we have reported on a new pathway to 2-substituted in-
doles.23,24 Our method contains Michael addition reactions between
1
2 n=1
4 n=1
3
5
n=2
n=2
Figure 1. Structures of granulatimide (1), vinilyindoles 4 and 5, and their cycloadducts
2 and 3.
Recently, we have synthesized new indoles 6–9 containing
3-vinyl functionality and investigated their reactivity (Scheme 1).21
The Diels–Alder reactivity of the 3-vinylindoles toward various
dienophiles leads to unusual Morita–Baylis–Hillman-type products
11–14, instead of the expected cycloadducts. Interesting mecha-
nistic and synthetic findings have encouraged us to investigate the
reactivity and synthesis of 2-vinylindoles 15–18 (Fig. 2). Herein, we
report our results.
4,7-dihydroindole19 and some a,b-unsaturated compoundsfollowed
by dehydrogenation. The Michael reaction is one of the most
importantandreliablecarbon–carbonand carbon–heteroatombond-
forming methods in organic synthesis.25 In addition, this type of re-
action has been investigated for the functionalization of indoles.26–34
In fact, our methodology has been used for the synthesis of asym-
metric 2-substituted indoles and functionalizations of indole.35–43
2. Results and discussions
To synthesize 2-vinylindole derivatives 15–18, firstly, 4,7-dihy-
droindole 19, the Birch reduction product of indole was obtained.
* Corresponding author. Tel.: þ90 442 231 4425; fax: þ90 442 236 0948.
E-mail address: nsarac@atauni.edu.tr (N. Saracoglu).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.080

T. Arslan et al. / Tetrahedron 66 (2010) 2936–2939
2937
Bi(NO3)3$5H2O-catalyzed reaction by cyclopent-2-one of the re-
duced indole 19 gave Michael adduct 24 (Scheme 2). In situ reaction
of adduct 24 with p-benzoquinone in acetonitrile yielded oxidation
product 28. In a similar manner we synthesized the corresponding
compounds 25–27 by starting from the appropriate unsaturated
cyclic ketone. After key compounds 24–27 were synthesized, the
preparation of the targeted indoles 15–18 was achieved by the
oxidation of 2-substitue indoles 24–27 with DDQ (2,3-dichloro-5,6-
dicyanobenzoquinone), which is a stronger oxidant (Scheme 2).
The structures for vinylindoles 15–18 are based on 1H, 13C NMR,
NOE 1H NMR, IR, and elemental analysis. For example, vinylindole
37 was confirmed by 1H NMR, 13C NMR, NOE 1H NMR, IR, and
elemental analysis.
NC
CN
Cl
O
O
O
DDQ
CH2Cl2
67%
N
H
N
H
nOe
33
H
O
H
15
X
16 was characterized by the presence of a NH signal at
d 9.04 ppm,
NC
CN
O
four benzene protons at 7.45–7.10 ppm, C3–H in the pyrrole ring at
6.95 ppm (d, J¼1.1 Hz), and alpha olefinic proton in cyclohexen-2-
one ring at 6.49 ppm (s). Furthermore CH2 protons resonated at
2.86 (t, J¼5.7 Hz), 2.55 (t, J¼5.7 Hz), and 2.18 (p, J¼5.7 Hz). The
observed coupling constant (4J¼1.1 Hz) between the NH and C3–H
in the pyrrole ring of 16 confirms the presence of substitution at the
C-2 position. The olefin geometry and placement of the substitution
in the pyrrole were established by differential 1H NMR nuclear
Overhauser enhancement (NOE) experiments. When the olefinic
O
O
N
H
32
Scheme 3.
proton (6.49 ppm) of 16 was irradiated, the NH at
a NOE signal, whereas a NOE was not observed between C3–H
(7.92 ppm) and olefinic (6.49 ppm) signals.
d 9.04 ppm gave
NC
NC
CN
CN
O
O
O
O
Cl
Cl
O
N
N
.
Bi(NO3)3 5H2O
H
35
H
34
+
O
n(CH2) CH2Cl2, rt
N
H
N
(74%)
(33%)
O
O
n(CH2)
H
19
20-23
n=1,2,3,4
24-27
Figure 3. 2,3-Disubstitue indoles 34 and 35.
n=1,2,3,4
p-benzoquinone
MeCN
Ph
N
Ph
N
O
O
O
O
DDQ
MeCN
N
NH
O
O
N
N
N
N
H
10
CH2Cl2
n(CH2)
n(CH2)
H
15-18
n(CH2)
n(CH2)
N
H
N
28-31
H
36-37
n=1 (31%)
n=2 (45%)
n=3 (28%)
n=4 (55%)
n=1 (75%)
n=2 (61%)
n=3 (46%)
n=4 (54%)
15-16
O
O
n= 1,2
n=1 (45%)
n=2 (50%)
Scheme 4.
Scheme 2.
Clearly, the dienophiles are not captured in cisoid conformation in
vinylindoles 15–18. On the other hand, transoid (T) structures for
vinylindoles 15–18 are more stable than cisoid (C) structures (Scheme
5). We assume that the dynamic equilibrium for 2-vinylindoles is to-
ward transoid structures due to the steric repulsion between C3–H of
indole ring and alpha-proton of cycloalken-2-one ring. A reasonable
mechanism leading to the formation of Michael addition products is
shownbelow, whereitmaywellproceedviazwitterion38(Scheme 5).
Subsequently, our experiments focused on the cycloaddition of
2-vinylindoles 15–18. When vinylindoles 15–18 were treated with
dieonophiles, such as maleic anhydride, dimethyl acetylenedi-
carboxylate, tetracyanoethylene, naphthoquinone, and p-benzo-
quinone under different conditions, unreacted starting materials
were recovered in every case. Due to the observed positive results,
we fully concentrated on the reaction of the vinylindoles with
N-phenyltriazolinedione (PTAD; 10) and DDQ.
Vinylindole 15 and DDQ were refluxed in methylene chloride for
five days (Scheme 3). After purification, all data showed that the
product is not exactly a cycloaddition product 32. The structure of
Michael-type adduct 33 was especially assigned on the basis of the
H
H
O
N
H
N
H
NOE observations. Irradiation of the NH at
d 11.61 ppm produced
15T
15C
O
a strong NOE for one of the aromatic protons at 7.42 ppm and the
olefinic proton in cyclopenten-2-one ring at 6.48 ppm. Similarly,
Michael adducts 34 and 35 were obtained from the reaction of
vinylindoles 16 and 18 with DDQ (Fig. 3).
Next, the reaction of 16 with PTAD was carried out in
dichloromethane at room temperature for 24 h to provide Michael
adduct 36 (Scheme 4). Under similar conditions, we obtained Mi-
chael adduct 37 from the reaction with PTAD of vinylindole 15
(Scheme 4). The relative configuration for Michael adducts 36 and
-O
N
O
Ph
Ph
O
N
N
N
N
N
O
H
+
-H
36
+
+
+H
N
H
N
H
O
O
15
38
Scheme 5.

2938
T. Arslan et al. / Tetrahedron 66 (2010) 2936–2939
3. Conclusions
(KBr, cmꢂ1) 3335, 2955, 1678, 1450, 1220. Anal. Calcd for C16H19NO:
C, 79.63; H, 7.94; N, 5.80. Found: C, 79.91; H, 7.79; N, 5.82.
In summary, we synthesized new 2-vinylindoles. It is remark-
able that Diels–Alder reactivity of these vinylindoles did not form
the expected cycloaddition products or unusual Morita–Baylis–
Hillman-type products observed for 3-vinyl analogs. However,
Michael addition products, 2,3-disubstitue indoles, were obtained.
4.1.5. 3-(1H-Indol-2-yl)cyclopent-2-enone (15). A solution of 28
(516 mg, 2.59 mmol) and DDQ (590 mg, 2.59 mmol) in 20 mL of dry
benzene was stirred at 0 ꢁC for 2 h. After the benzene was evapo-
rated, the crude product was dissolved in CH2Cl2 (50 mL) and or-
ganic phase was washed with NaHCO3 (2ꢀ50 mL), water
(2ꢀ25 mL) and dried over Na2SO4. After removal of the solvent,
crude product 15 was recrystallized from acetone/hexane. (157 mg,
31%, pale yellow crystals, mp 179–180 ꢁC): 1H NMR (400 MHz,
4. Experimental section
4.1. General methods
DMSO-d6):
d
11.66 (m, NH, 1H), 7.60 (d, J¼7.9 Hz, ]CH, 1H), 7.41 (d,
Melting points were determined on Buchi 539 capillary melting
apparatus. Infrared spectra were recorded on a Mattson 1000 FT-IR
spectrophotometer. 1H NMR and 13C NMR spectra were recorded on
200 (50) and 400 (100)-MHz Varian spectrometer and are reported
in d units with SiMe4 as internal standard. Elemental analyses were
carried out on a Leco CHNS-932 instrument.
J¼7.9 Hz, ]CH, 1H), 7.22 (t, J¼7.9 Hz, ]CH, 1H), 7.05–7.02 (m, ]CH,
2H), 6.55 (s, ]CH, 1H), 3.04–3.02 (m, CH2, 2H), 2.44–2.42 (m, CH2,
2H). 13C NMR (100 MHz, DMSO-d6):
d 208.7, 165.6, 138.9, 133.8,
128.4, 125.2, 125.0, 122.1, 120.6, 112.4, 106.3, 35.2, 28.4. IR (KBr,
cmꢂ1) 3251, 2919, 2230, 1653, 1590, 1451, 1342, 1280, 1196, 1079.
Anal. Calcd for C13H11NO: C, 79.16; H, 5.62; N, 7.10. Found: C, 79.13;
H, 5.41; N, 7.38.
4.1.1. 3-(1H-Indol-2-yl)cyclopentanone (28). A solution of 4,7-
dihydro-1H-indole (19; 500 mg, 4.20 mmol), cyclopent-2-en-1-one
(20; 345 mg, 4.20 mmol) and catalytic amount of Bi(NO3)3$5H2O in
CH2Cl2 (15 mL) was stirred magnetically at room temperature for
16 h. After completion of the reaction, the mixture was diluted with
dichloromethane (30 mL) and washed with water (2ꢀ50 mL), and
organic phase was dried over Na2SO4. The crude product (790 mg;
93%) was dissolved in CH2Cl2 (15 mL) and p-benzoquinone
(636 mg, 5.88 mmol) was added. The mixture was stirred at the
room temperature for two days. After completion of the reaction,
the solvent was evaporated and crude product was dissolved with
ethyl acetate (30 mL) and the organic phase was washed with
NaOH (2 N, 2ꢀ30 mL), brine (30 mL), and dried over Na2SO4. The
solvent was evaporated to give 3-(1H-indol-2-yl)cyclopentanone
(2823; 590 mg, 75%).
4.1.6. 3-(1H-Indol-2-yl)cyclohex-2-enone (16). The vinylindole 16
was prepared as described for 15. For 16 (65 mg, 45%, pale pink
crystals, mp 201–203 ꢁC from ether): 1H NMR (400 MHz, CDCl3):
d
9.04 (m, NH, 1H), 7.45 (dd, J¼8.2, 0.9 Hz, ]CH, 1H), 7.30–7.26 (m,
]CH, 1H), 7.14–7.10 (m, ]CH, 1H), 6.95 (d, J¼1.1 Hz, ]CH, 1H), 6.49
(s, ]CH, 1H), 2.86 (t, J¼5.7 Hz, CH2, 2H), 2.55 (t, J¼5.7 Hz, CH2, 2H),
2.18 (p, J¼5.7 Hz, CH2, 2H). 13C NMR (100 MHz, CDCl3):
d 199.8,
150.7, 138.2, 135.5, 128.6, 125.1, 121.7, 121.1, 120.8, 111.7, 106.9, 37.8,
26.8, 22.7. IR (KBr, cmꢂ1) 3305, 2929, 2364, 1641, 1591. Anal. Calcd
for C14H13NO: C, 79.59; H, 6.20; N, 6.63. Found: C, 79.73; H, 6.47; N,
7.39.
4.1.7. 3-(1H-Indol-2-yl)cyclohept-2-enone (17). The vinylindole 17
was prepared as described for 15. For 17 (192 mg, 28%, dark brown
crystals from acetone/hexane, mp 76–77 ꢁC): 1H NMR (400 MHz,
4.1.2. 3-(1H-Indol-2-yl)cyclohexanone (29). 3-(1H-Indol-2-yl)cyclo-
hexanone (2923; 145 mg, 61%) was prepared from 4,7-dihydro-1H-
indole (19; 200 mg, 1.67 mmol) and cyclohex-2-en-1-one (21,
161 mg, 1.67 mmol) as described for the preparation of 28.
DMSO-d6):
d
11.42 (m, NH, 1H), 7.53 (d, J¼7.9 Hz, ]CH, 1H), 7.33 (d,
J¼7.9 Hz, ]CH, 1H), 7.14 (t, J¼7.9 Hz, ]CH, 1H), 7.00–6.96 (m, ]CH,
2H), 6.55 (s, ]CH, 1H), 2.94–2.91 (m, CH2, 2H), 2.60–2.57 (m, CH2,
2H), 1.85–1.80 (m, CH2, 2H), 1.78–1.73 (m, CH2, 2H). 13C NMR
(100 MHz, DMSO-d6): d 203.7, 148.0, 138.9, 138.1, 128.6, 125.8, 124.3,
4.1.3. 3-(1H-Indol-2-yl)cycloheptanone (30). The Micheal adduct
30 was prepared as described for 28. For 30 (492 mg, 46%, dark
brown crystals from CH2Cl2/hexane, mp 134–135 ꢁC): 1H NMR
121.6, 120.3, 112.1, 106.1, 42.0, 28.7, 25.1, 21.2. IR (KBr, cmꢂ1) 3311,
2936, 2863, 1631, 1591, 1510, 1448, 1418, 1285, 1183, 798, 749. Anal.
Calcd for C15H15NO: C, 79.97; H, 6.71; N, 6.22. Found: C, 80.13; H,
6.82; N, 6.01.
(400 MHz, CDCl3):
d
8.12 (m, NH, 1H), 7.54 (d, J¼7.4 Hz, ]CH, 1H),
7.30 (d, J¼7.4 Hz, ]CH, 1H), 7.14 (br t, J¼7.4 Hz, ]CH, 1H), 7.08 (br t,
J¼7.4 Hz, ]CH, 1H), 6.27–6.26 (m, ]CH, 1H), 3.17–3.11 (m, CH, 1H),
2.97 (dd, J¼14.2, 10.4 Hz, A part of AB system, CH2, 1H), 2.88 (dd,
J¼14.2,1.6 Hz, B part of AB system, CH2, 1H), 2.60–2.57 (m, CH2, 2H),
2.29–2.45 (m, CH2, 1H), 2.08–2.00 (m, CH2, 1H), 1.98–1.92 (m, CH2,
1H), 1.89–1.81 (m, CH2, 1H), 1.78–1.61 (m, CH2, 1H), 1.59–1.52 (m,
4.1.8. (E)-3-(1H-Indol-2-yl)cyclooct-2-enone (18). The vinylindole
18 was prepared as described for 15. For 18 (120 mg, 55%, yellow
crystals from acetone/hexane, mp 163–164 ꢁC): 1H NMR (400 MHz,
DMSO-d6):
d
8.72 (m, NH, 1H), 7.60 (br d, J¼8.0 Hz, ]CH, 1H), 7.38
(dd, J¼8.0, 0.7 Hz, ]CH, 1H), 7.26 (td, J¼8.0, 1.1 Hz, ]CH, 1H), 7.10
(td, J¼8.0, 1.1 Hz, ]CH, 1H), 6.93 (d, J¼1.5 Hz, ]CH, 1H), 6.66 (s,
]CH, 1H), 3.19 (t, J¼7.0 Hz, CH2, 2H), 2.96 (t, J¼7.3 Hz, CH2, 2H),
1.87–1.78 (m, CH2, 4H), 1.66–1.60 (m, CH2, 2H). 13C NMR (100 MHz
CH2, 1H). 13C NMR (100 MHz, CDCl3):
d 213.4, 142.9, 136.1, 128.6,
121.7, 120.3, 120.0, 110.8, 98.7, 49.6, 44.2, 37.1, 35.9, 28.5, 24.2. IR
(KBr, cmꢂ1) 3390, 3053, 2927, 2857, 1686, 1617, 1584, 1544, 1457,
784, 746. Anal. Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found:
C, 79.42; H, 7.41; N, 7.39.
DMSO-d6): d 202.2, 143.5, 138.9, 138.6, 128.7, 128.0 (CH), 124.2 (CH),
121.5 (CH), 120.3 (CH), 112.2 (CH), 106.0 (CH), 42.8 (CH2), 29.1 (CH2),
25.5 (CH2), 23.4 (2CH2). IR (KBr, cmꢂ1) 3333, 2924, 1737, 1617, 1578,
1364, 1216. Anal. Calcd for C16H17NO: C, 80.30; H, 7.16; N, 5.85.
Found: C, 80.13; H, 7.01; N, 5.97.
4.1.4. 3-(1H-Indol-2-yl)cyclooctanone (31). The Micheal adduct 31
was synthesized as described for 28. For 31 (220 mg, 54%, dark
brown crystals from CH2Cl2/hexane, mp 155–156 ꢁC): 1H NMR
(400 MHz, CDCl3):
d
8.37 (m, NH, 1H), 7.54 (d, J¼7.9 Hz, ]CH, 1H),
4.1.9. 4-Chloro-3,6-dioxo-5-(2-(3-oxocyclopent-1-enyl)-1H-indol-3-
yl)cyclohexa-1,4-diene-1,2-dicarbonitrile (33). A solution of 15
(155 mg, 0.79 mmol) and DDQ 178 mg (0.79 mmol) in 20 mL CH2Cl2
was refluxed for five days. After CH2Cl2 was evaporated, acetone
(15 mL) was added to the reaction mixture. The solution with ac-
etone was decanted and the precipitate was dried on paper filter
was dried over room conditions to give 33 (206 mg, 67%, yellow
7.32 (dd, J¼7.9, 1.1 Hz, ]CH, 1H), 7.16–7.06 (m, ]CH, 2H), 6.27–6.26
(m, ]CH, 1H), 3.38–3.33 (m, CH, 1H), 2.96–2.90 (m, CH2, 1H), 2.75–
2.74 (m, CH2, 1H), 2.72–2.43 (m, CH2, 2H), 2.12–2.04 (m, CH2, 2H),
1.98–1.93 (m, CH2, 1H), 1.77–1.57 (m, CH2, 4H), 1.45–1.41 (m, CH2,
1H). 13C NMR (100 MHz, CDCl3):
d
216.2, 143.4, 136.0, 128.6, 121.6,
120.2, 120.0, 110.9, 98.5, 46.1, 44.0, 38.4, 33.5, 28.1, 24.4, 24.4. IR

T. Arslan et al. / Tetrahedron 66 (2010) 2936–2939
2939
crystals, mp 232–233 ꢁC): 1H NMR (400 MHz, DMSO-d6):
d
11.61 (br
2H). 13C NMR (100 MHz, DMSO-d6):
d
199.1, 152.5, 152.0, 149.9,
s, NH, 1H), 7.42 (d, J¼7.9 Hz, ]CH, 1H), 7.22 (t, J¼7.9 Hz, ]CH, 1H),
6.91 (t, J¼7.9 Hz, ]CH, 1H), 6.73 (d, J¼7.9 Hz, ]CH, 1H), 6.58 (s,
]CH, 1H), 3.16–3.14 (m, CH2, 2H), 2.46–2.44 (m, CH2, 2H). 13C NMR
135.8,133.9,132.5,129.6,128.8,127.1,125.6,125.4,125.2,121.5,119.1,
113.0, 112.4, 37.6, 26.5, 22.9. IR (KBr, cmꢂ1) 3338, 2918, 2857, 1776,
1700, 1619, 1577, 1488, 1412, 1258, 1127. Anal. Calcd for C22H18N4O3:
C, 68.38; H, 4.70; N, 14.50. Found: C, 68.63; H, 4.68; N, 14.56.
(100 MHz, DMSO-d6): d 208.3, 163.4, 157.2, 147.2, 137.3, 135.7, 132.7,
130.9, 126.3, 125.7, 121.2, 118.0, 114.6, 113.4, 112.8, 106.8, 102.5, 34.9,
29.3. IR (KBr, cmꢂ1) 3288, 2924, 2224, 1650, 1586, 1446. Anal. Calcd
for C21H10ClN3O3: C, 65.04; H, 2.60; N, 10.84. Found: C, 64.93; H,
2.89; N, 11.03.
Acknowledgements
We are greatly indebted to The Scientific and Technical Research
Council of Turkey (TUBITAK, Grant No. TBAG-107T073) for their
financial support for this work.
4.1.10. 4-Chloro-3,6-dioxo-5-(2-(3-oxocyclohex-1-enyl)-1H-indol-3-
yl)cyclohexa-1,4-diene-1,2-dicarbonitrile (34). The Michael adduct
34 was prepared as described for 33. For 34 (140 mg, 74%, orange
crystals from acetone, mp 230–232 ꢁC): 1H NMR (400 MHz, DMSO-
Supplementary data
d6):
d
11.54 (br s, NH, 1H), 7.39 (d, J¼7.8 Hz, ]CH, 1H), 7.17 (t,
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.02.080.
J¼7.8 Hz, ]CH, 1H), 6.88 (t, J¼7.8 Hz, ]CH, 1H), 6.68 (d, J¼7.8 Hz,
]CH, 1H), 6.57 (s, ]CH, 1H), 2.92 (t, J¼5.7 Hz, CH2, 2H), 2.38 (t,
J¼6.6 Hz, CH2, 2H), 2.08–2.01 (m, CH2, 2H). 13C NMR (100 MHz,
References and notes
DMSO-d6):
d 198.9, 156.8, 150.0, 147.6, 136.5, 135.1, 132.6, 130.8,
1. Pindur, U. In Advances in nitogen Heterocycles; Moddy, C. J., Ed.; JAI: Greenwich,
1995; Vol. 1, pp 121–172.
125.1, 123.7, 123.3, 121.0, 118.5, 117.6, 114.5, 113.2, 112.7, 106.5, 102.8,
37.6, 27.0, 22.8. IR (KBr, cmꢂ1) 3355, 2935, 2229, 1711, 1619, 1583,
1412, 1356, 1239. Anal. Calcd for C22H12ClN3O3: C, 65.76; H, 3.01; N,
10.46. Found: C, 65.90; H, 3.07; N, 10.38.
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3. Pfeuffer, L.; Pindur, U. Helv. Chim. Acta 1987, 70, 1419–1428.
4. Eitel, M.; Pindur, U. J. Org. Chem. 1990, 55, 5368–5374.
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J. J.; Rieger, D. L. Tetrahedron 1996, 52, 4555–4572.
4.1.11. (E)-4-Chloro-3,6-dioxo-5-(2-(3-oxocyclooct-1-enyl)-1H-indol-
3-yl)cyclohexa-1,4-diene-1,2-dicarbonitrile (35). The vinylindole 35
was prepared as described for 33. For 35 (60 mg, 33%, yellow
crystals from acetone, mp 185–186 ꢁC): 1H NMR (400 MHz, DMSO-
6. Beccalli, E. M.; Marchesini, A. Tetrahedron 1996, 52, 3029–3036.
7. Dufour, B.; Motorina, I.; Fowler, F. W.; Grierson, D. S. Heterocycles 1994, 37,
1455–1458.
8. Pindur, U. Heterocycles 1988, 27, 1253–1268.
´
´
9. Joseph, B.; Da Costa, H.; Merour, J.-Y.; Leonce, S. Tetrahedron 2000, 56, 3189–
3196.
d6):
d
11.38 (m, NH, 1H), 7.36 (dd, J¼7.2 Hz, 1.0 Hz, ]CH, 1H), 7.15
10. Rodriguez-Salvador, L.; Zaballos-Garcia, E.; Gonzalez-Rosende, E.; Djebouri Sidi,
M.; Sepulveda-Arques, J.; Jones, R. A. Synth. Commun. 1997, 27, 1439–1447.
11. Balasubramanian, T.; Balasubramanian, K. K. Chem. Commun. 1994, 1237–1238.
12. Macor, J. E. Heterocycles 1990, 31, 993–998.
13. Madalengoitia, J. S.; Macdonald, T. L. Tetrahedron Lett. 1993, 34, 6237–6240.
14. Blechert, S.; Wirth, T. Tetrahedron Lett. 1992, 33, 6621–6624.
15. Wiest, O.; Steckhan, E. Angew. Chem., Int. Ed. Engl. 1993, 32, 901–903.
16. Elango, S.; Srinivasan, P. C. Tetrahedron Lett. 1993, 34, 1347–1350.
17. Padwa, A.; Lynch, S. M.; Mejia-Oneto, J. M.; Zhang, H. J. Org. Chem. 2005, 70,
2206–2218.
(td, J¼7.2, 1.0 Hz, ]CH, 1H), 6.88 (td, J¼7.2, 1.0 Hz, ]CH,1H), 6.71 (s,
]CH, 1H), 6.67 (d, J¼7.2 Hz, ]CH, 1H), 3.22 (t, J¼6.6 Hz, CH2, 2H),
2.82 (t, J¼7.2 Hz, CH2, 2H), 1.74–1.69 (m, CH2, 4H), 1.53–1.52 (m,
CH2, 2H). 13C NMR (100 MHz, DMSO-d6):
d 202.5, 157.4, 147.0, 142.6,
135.6, 134.5, 132.3, 131.11, 131.1, 125.5, 124.6, 120.8, 118.8, 117.3,
114.9, 113.1, 112.8, 105.9, 102.2, 43.0, 28.9, 24.5, 23.7, 23.5. IR (KBr,
cmꢂ1) 3338, 2941, 2302, 2235, 1622, 1580, 1530, 1415, 1348, 1328,
1269, 1239, 1194, 1169. Anal. Calcd for C24H16ClN3O3: C, 67.06; H,
3.75; N, 9.78. Found: C, 67.31; H, 3.62; N, 10.01.
18. Rosillo, M.; Dominguez, G.; Casarrubios, L.; Amador, U.; Perez-Castells, J. J. Org.
Chem. 2004, 69, 2084–2093.
19. Pfeuffer, L.; Pindur, U. Helv. Chim. Acta 1988, 71, 467–471.
20. Conchon, E.; Anizon, F.; Aboab, B.; Prudhomme, M. J. Med. Chem. 2007, 50,
4669–4680.
21. Sadak, A. E.; Arslan, T.; Celebioglu, N.; Saracoglu, N. Tetrahedron, in press.
doi:10.1016/j.tet.2010.02.081
4.1.12. 1-(2-(3-Oxocyclopent-1-enyl)-1H-indol-3-yl)-4-phenyl-1,2,4-
triazolidine-3,5-dione (36). A solution of 15 (160 mg, 0.81 mmol)
and PTAD (142 mg, 0.81 mmol) in CH2Cl2 (20 mL) was stirred
magnetically at room temperature for 24 h. After CH2Cl2 was
evaporated, acetone (15 mL) was added to the reaction mixture.
The solution with acetone was decanted and the precipitate was
filtered and dried to give 36 (135 mg, 45%, pale yellow crystals, mp
22. Scopes, D. I. C.; Allen, M. S.; Hignett, G. J.; Wilson, N. D. V.; Harris, M.; Joule, J. A.
J. Chem. Soc., Perkin Trans. 1 1977, 2376–2385.
23. Çavdar, H.; Saraçog˘lu, N. Tetrahedron 2005, 61, 2401–2405.
24. Cavdar, H.; Saracoglu, N. J. Org. Chem. 2006, 71, 7793–7799.
25. Lewandowska, E. Tetrahedron 2006, 63, 2107–2122.
26. Saracoglu, N. Top. Heterocycl. Chem. 2007, 11, 1–61.
27. Agnusdei, M.; Bandini, M.; Melloni, A.; Umani-Ronchi, A. J. Org. Chem. 2003, 68,
7126–7719.
28. Harrington, P.; Kerr, M. A. Synlett 1996, 1047–1050.
29. Harrington, P.; Kerr, M. A. Can. J. Chem. 1998, 76, 1256–1265.
30. Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G. Synthesis 2001, 2165–2169.
31. Bandini, M.; Melchiorre, P.; Melloni, A.; Umani-Ronchi, A. Synthesis 2002, 1110–
1114.
32. Bandini, M.; Fagioli, M.; Melloni, A.; Umani-Ronchi, A. Synthesis 2003, 397–402.
33. Yadav, J. S.; Reddy, B. V. S.; Swamy, T. Synthesis 2004, 106–110.
34. Alam, M. M.; Varala, R.; Adapa, S. R. Tetrahedron Lett. 2003, 44, 5115–5119.
35. Hong, L.; Liu, C.; Sun, W.; Wang, L.; Wong, K.; Wang, R. Org. Lett. 2009, 11, 2177–
2180.
285–286 ꢁC): 1H NMR (400 MHz, DMSO-d6):
d 12.15 (m, NH, 1H),
11.46 (m, NH, 1H), 7.61–7.50 (m, ]CH, 6H), 7.43 (br t, J¼7.3 Hz,
]CH, 1H), 7.33 (br t, J¼7.3 Hz, ]CH, 1H), 7.16 (br t, J¼7.3 Hz, ]CH,
1H), 6.72 (d, J¼1.5 Hz, ]CH, 1H), 3.28–3.15 (m, CH2, 2H), 2.50–2.48
(m, CH2, 2H). 13C NMR (100 MHz, DMSO-d6):
d 208.9, 163.5, 152.0,
146.1, 136.4, 130.6, 130.3, 130.2, 129.5, 128.3, 127.5, 126.9, 125.7,
125.2 121.5, 119.7, 113.1, 35.1, 28.6. IR (KBr, cmꢂ1) 3225, 2901, 2847,
1752, 1603, 1558, 1468, 1392, 1258, 1048, 987. Anal. Calcd for
C21H16N4O3: C, 67.73; H, 4.33; N, 15.05. Found: C, 67.95; H, 4.30; N,
14.93.
36. Blay, G.; Ferna´ndez, I.; Monleo´ n, A.; Pedro, J. R.; Vila, C. Org. Lett. 2009, 11,
441–444.
37. Zeng, M.; Kang, Q.; He, Q.-L.; You, S.-L. Adv. Synth. Catal. 2008, 350,
2169–2173.
38. Kang, Q.; Zheng, X.-J.; You, S.-L. Chem.dEur. J. 2008, 14, 3539–3542.
39. Blay, G.; Fernandez, I.; Pedro, J. R.; Vila, C. Tetrahedron Lett. 2007, 48, 6731–6734.
40. Evans, D. A.; Fandrick, K. R.; Song, H.-J.; Scheidt, K. A.; Xu, R. J. Am. Chem. Soc.
2007, 129, 10029–10041.
41. Takenaka, N.; Sarangthem, R. S.; Seerla, S. K. Org. Lett. 2007, 9, 2819–2822.
42. Evans, D. A.; Fandrick, K. R. Org. Lett. 2006, 8, 2249–2252.
43. Cho, S. H.; Chang, S. Angew. Chem., Int. Ed. 2008, 47, 2836–2839.
4.1.13. 1-(2-(3-Oxocyclohex-1-enyl)-1H-indol-3-yl)-4-phenyl-1,2,4-
triazolidine-3,5-dione (37). The Michael adduct 37 was prepared as
described for 36. For 37 (90 mg, 50%, pale yellow crystals from ac-
etone, mp 225–226 ꢁC): 1H NMR (400 MHz, DMSO-d6):
d 11.95 (m,
NH, 1H), 7.56–7.41 (m, ]CH, 7H), 7.28 (dd, J¼8.2, 7.2 Hz, ]CH, 1H),
7.12 (t, J¼7.2 Hz, ]CH, 1H), 6.51 (d, J¼0.8 Hz, ]CH, 1H), 2.87 (t,
J¼5.7 Hz, CH2, 2H), 2.41 (t, J¼6.4 Hz, CH2, 2H), 2.07–2.06 (m, CH2,