Zirconium triflate-catalyzed reactions of indole, 1-methylindole, and pyrrole with α,β-unsaturated ketone

Article abstract of DOI:10.1016/j.tet.2004.05.087

The Zr(OTf)₄-catalyzed reaction of indole, 1-methylindole or pyrrole with α,β-unsaturated ketone generated the corresponding trisindolyl-, tris(1-methylindolyl-), and trispyrrolylalkanes in moderate to high yields in the mixed solvent EtOH/H

Full text of DOI:10.1016/j.tet.2004.05.087

Tetrahedron 60 (2004) 6679–6684
Zirconium triflate-catalyzed reactions of indole, 1-methylindole,
and pyrrole with a,b-unsaturated ketone
*
Min Shi, Shi-Cong Cui and Qing-Jiang Li
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fengli Lu, Shanghai 200032, China
Received 8 May 2004; revised 21 May 2004; accepted 21 May 2004
Available online 19 June 2004
Abstract—The Zr(OTf)4-catalyzed reaction of indole, 1-methylindole or pyrrole with a,b-unsaturated ketone generated the corresponding
trisindolyl-, tris(1-methylindolyl-), and trispyrrolylalkanes in moderate to high yields in the mixed solvent EtOH/H2O.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
1,4-addition (Michael addition) product 3a in 30% yield
in the presence of Yb(OTf)3 (5 mol%) under solvent free
conditions (Scheme 1).4 So far the formation of a
triindolylalkane has been reported only in the reaction of
1-methylindole with 3-methyl-2-cyclohexene-1-one to give
triindolylcyclohexane in low yield as a byproduct under
vigorous conditions.5 Herein, we wish to report this
interesting three indole-addition reaction in the presence
of various metal triflate Lewis acids under mild conditions.
The Michael addition reaction is one of the most important
C–C bond forming reactions in organic chemistry.1
Recently, many high-yielding, environmentally-benign,
oxygen and moisture tolerant Lewis acids such as
Ln(OTf)3 (Ln¼Yb, Sc, Y, La, etc.) or bismuth nitrate
[Bi(NO3)3] have been applied to this transformation.2
Among them the addition of indole to electron-deficient
olefins is a widely investigated process because this reaction
is involved in the total synthesis of a class of bioactive
indole alkaloids known as the hapalindoles.2,3 However, in
our ongoing investigations of this interesting reaction, we
found that this typical Michael addition reaction become
complicated in the presence of excess amounts of indoles.
For example, in the reaction of indole 1a (1.5 equiv.) with
2-cyclohexen-1-one 2a (1.0 equiv.), this reaction produces
product 4a in which three indole moieties have been
incorporated, in 25% yield via a 1,4-addition, 1,2-addition
and a dehydration process, along with the normal
2. Results and discussion
The promoters for the reaction of indole 1a (3.0 equiv.) with
2-cyclohexen-1-one 2a (1.0 equiv.) were systematically
examined at first in neat 2-cyclohexen-1-one in the absence
of organic solvent. The results are summarized in Table 1.
We found that in the reaction of indole 1a (3.0 equiv.) with
2-cyclohexen-1-one 2a (1.0 equiv.), the major reaction
product was compound 4a in the presence of various
Scheme 1.
Keywords: Indole; Pyrrole; a,b-Unsaturated ketone; Zr(OTf)4; Lewis acid; Michael addition; Trisindolylalkane.
*
Corresponding author. Tel.: þ86-21-64163300x342; fax: þ86-21-64166128; e-mail address: mshi@pub.sioc.ac.cn
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.087

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M. Shi et al. / Tetrahedron 60 (2004) 6679–6684
Table 1. The reaction indole 1a (3.0 equiv.) with 2-cyclohexen-1-one 2a (1.0 equiv.) in the presence of Lewis acid
Entrya
Lewis acid
Yield [%]b
3a
4a
1
2
3
4
5
6
7
8
Yb(OTf)3
Sc(OTf)3
Eu(OTf)3
Zr(OTf)4
Hf(OTf)4
Cu(OTf)2
Sn(OTf)2
Ti(OPrj)4
30
23
26
20
27
27
32
NR
43
53
38
60
45
36
36
a
The reaction was carried out in neat 2-cyclohexene-1one without organic solvent.
Isolated yields.
b
metal triflate Lewis acids (Table 1, entries 1–7). The Lewis
acid Ti(OiPr)4 showed no catalytic activity for this
reaction (Table 1, entry 8). Zr(OTf)4 gave the best result
under identical conditions. The three indole-incorporated
product 4a can be isolated in 60% yield under mild
conditions using Zr(OTf)4 as a Lewis acid promoter (Table
1, entry 4).
alkane 4b was obtained in low yield under the same
conditions even after a prolonged reaction time (Table 2,
entry 2). This may be due to the rigid five-membered ring,
which disfavors the 1,4- or 1,2-addition of sterically-
demanding indoles in the presence of Lewis acid. On
the other hand, using 1-methylindole 1b to react with
2-cyclohexene-1-one 2a or crotonaldehyde 2d under the
same conditions, similar results were obtained (Table 2,
entries 3 and 7), although in the reaction of 1b with acrolein
2c and trans-cinnamaldehyde 2e, the corresponding tri-
indolylalkanes 4e and 4i were obtained in lower yields
(Table 2, entries 5 and 9). It should be emphasized here that
in the case of the reaction of 1b with 2e, product 4j in which
two 1-methylindole moieties were incorporated was isolated
as a major product in 28% yield (Scheme 3). Using pyrrole
1c instead of indole, the corresponding tripyrrolylcyclo-
hexane 4k was formed in 40% under the same conditions
(Table 2, entry 10). In addition, the reaction of indole
(5.0 equiv.) with methyl vinyl ketone (1.0 equiv.) produced
the corresponding triindolylalkane 4l under the same
conditions, although the isolated yield was 8% (Table 2,
entry 11).
In order to improve the isolated yield of 4a, solvent effects
were examined in various organic solvents in the presence
of Zr(OTf)4 (5 mol%). We found that in the mixed polar
solvent EtOH/H2O (2/1), the isolated yield of 4a can reach
87% in the presence of Zr(OTf)4 (5 mol%) along with 5% of
3a under mild conditions (Scheme 2).
Scheme 2.
The mechanism for this three indole or pyrrole incorpo-
rating reaction is shown in Scheme 3. The 1,4- and
1,2-additions of indole to a,b-unsaturated ketone take
place sequentially to give intermediate A in the presence of
Lewis acid Zr(OTf)4 (Scheme 3). The dehydration of A
gives another intermediate B which is further activated
by Lewis acid Zr(OTf)4 and serves as an electrophile to
react with a third molecule of indole, affording intermediate
C. The corresponding three indole-incorporated product is
subsequently formed from intermediate C (Scheme 4). We
confirmed that product 3a can be completely transformed to
4a in the presence of Zr(OTf)4 and indole under the same
conditions (Scheme 4). Thus, this result supports the
proposed reaction mechanism.
Under these optimized reaction conditions, we next
examined the reactions of indole 1a (5.0 equiv.), 1-methyl-
indole 1b (5.0 equiv.), pyrrole 1c (5.0 equiv.) with various
a,b-unsaturated ketone (1.0 equiv.) in the presence of
Zr(OTf)4 (5 mol%). The results are summarized in Table
2. As can be seen from Table 2, the yields of triindolyl-
alkanes are very sensitive to the substrates employed (Table
2, entries 1–11). Using acrolein 2c, crotonaldehyde 2d,
trans-cinnamaldehyde 2e as substrates, the corresponding
triindolylalkanes 4d, 4f and 4h were produced in moderate
to good yields (Table 2, entries 4, 6, and 8). Their yields
could be slightly improved by prolonging the reaction time
(3 days). For the reaction of indole 1a with 2-cyclohexene-
1-one 2a, the triindolylalkane 4a was obtained in 99% yield
after 3 days under the same conditions (Table 2, entry 1).
For 2-cyclopenten-1-one 2b, the corresponding triindolyl-
In conclusion, we found that in the reaction of excess
amounts of indole, 1-methylindole or pyrrole with

M. Shi et al. / Tetrahedron 60 (2004) 6679–6684
6681
Table 2. Reactions of indole, l-methylindole or pyrrole with a,b-unsaturated ketones in the presence of Zr(OTf)4
Entrya
Time/[days]
Yield [%]b, 4a–4l
1
2
3
1a
1b
2a
2b
3
3
3
4a, 99
4b, 4
1a
2a
4c, 80
4
5
6
7
1a
1b
1a
1b
2c
1 (3)
3
4d, 50 (53)
4e, 20
2c
2d
1 (3)
3
4f, 60 (61)
4g, 63
2d
8
1a
1b
2e
1 (3)
4h, 70 (80)
9
2e
2a
3
3
4i, 15c
4k, 40
10
1c
11
1a
2f
3
4l, 8
a
Zr(OTf)4 (5.0 mol%), 1a–c (5.0 equiv.) and a,b-unsaturated ketones (1.0 equiv.) were dissolved in 1.0 mL of EtOH/H20(2/1) solvent.
Isolated yields.
Anothere product 4j was isolated in 28% yield.
b
c
Scheme 3.
a,b-unsaturated ketone the trisindolyl- or trispyrrolylalk-
anes can be produced in the presence of Lewis acid
Zr(OTf)4 under mild conditions. Although the isolated
yields are highly dependent on the employed substrates, this
reaction pathway is interesting and the products obtained are
novel. Efforts are underway to elucidate the mechanistic
details of this catalytic system and to extend the scope of
this interesting reaction.

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M. Shi et al. / Tetrahedron 60 (2004) 6679–6684
Scheme 4.
1
3. Experimental
3.1. General methods
1104 cm21; H NMR (CDCl3, 300 MHz, TMS): d 1.63–
1.74 (1H, m, CH2), 1.81–2.02 (2H, m, CH2), 2.15–2.47
(3H, m, CH2), 2.98–3.08 (1H, m, CH), 3.28–3.35 (2H, m,
CH2), 6.88–6.92 (3H, m, ArH), 6.96–7.18 (5H, m, ArH),
7.24–7.28 (1H, m, ArH), 7.34 (2H, t, J¼8.0 Hz, ArH), 7.46
(2H, m, ArH), 7.54 (1H, d, J¼7.9 Hz, ArH), 7.67 (1H, d,
J¼8.1 Hz, ArH), 7.81 (1H, s, NH), 7.89 (1H, s, NH), 8.11
(1H, s, NH); 13C NMR (CDCl3, 75 MHz): d 23.3, 31.0, 34.0,
36.6, 40.3, 43.9, 111.1, 111.1, 111.2, 118.5, 118.6, 118.9,
119.4, 119.6, 119.6, 120.4, 120.8, 121.1, 121.2, 121.4,
121.8, 121.9, 122.7, 123.2, 125.8, 126.3, 126.7, 136.3,
137.0, 137.0; MS (EI) m/z 429 (Mþ, 44.19), 312 (Mþ2117,
90.34), 143 (Mþ2286, 100). Anal. calcd for C30H33N3:
requires C, 83.88; H, 6.34; N, 9.78. Found: C, 83.74; H,
6.21; N, 9.65%.
1
Melting points are uncorrected. H and 13C NMR spectra
were recorded at 300 and 75 MHz, respectively. Mass
spectra were recorded by EI methods, and HRMS were
measured on a Finnigan MAþ mass spectrometer. Organic
solvents used were dried by standard methods when
necessary. The solid compounds reported in this paper
gave satisfactory CHN microanalyses. Commercially
available reagents were used without further purification.
All reactions were monitored by TLC with Huanghai GF254
silica gel coated plates. Flash column chromatography was
carried out using 300–400 mesh silica gel at increased
pressure.
3.1.2. 1,1,3-Tris(3-indolyl)cyclopropane 4b. This com-
pound was isolated by flash chromatography to give 4b as a
white powder (eluent: petroleum ether/ethyl acetate¼4/1).
8.3 mg, yield: 4%.
A typical reaction procedure for the reaction of indole with
2-cyclohexen-1-one in the presence of Zr(OTf)4. Lewis acid
Zr(OTf)4 (5.0 mol%) and indole (292.3 mg, 2.5 mmol) were
dissolved in 1.0 mL of EtOH/H2O (2/1) mixed solvent.
2-Cyclohexene-1-one (34.5 mg, 0.5 mmol) was added
dropwise into the reaction system by a syringe and the
reaction mixture was stirred at room temperature for 3 days.
The solvent was removed under reduced pressure and the
residue was purified by silica gel column chromatography to
give 1,1,3-tris(3-indolyl)cyclohexane 4a as a white solid.
1
IR (KBr) n 3053, 2926, 2854, 1465, 1265 cm21; H NMR
(CD3COCD3, 300 MHz, TMS): d 2.09–2.19 (1H, m, CH2),
2.39–2.78 (3H, m, CH2), 2.91–3.20 (1H, m, CH2), 3.15–
3.24 (1H, m, CH2), 3.60–3.74 (1H, m, CH), 6.73–6.80 (2H,
m, ArH), 6.90–6.99 (3H, m, ArH), 7.02–7.09 (1H, m,
ArH), 7.15–7.17 (1H, m, ArH), 7.29–7.39 (3H, m, ArH),
7.47–7.60 (5H, m, ArH), 9.91 (2H, s, NH), 10.04 (1H, s,
NH); MS (EI) m/z 415 (Mþ, 24.23), 298 (Mþ2117, 87.24),
129 (Mþ2286, 100); HRMS (EI) calcd for C28H25N3
415.2049. Found: 415.2034.
3.1.1. 1,1,3-Tris(3-indolyl)cyclohexane 4a. This com-
pound was isolated by flash chromatography to give 4a as
a white solid (eluent: petroleum ether/ethyl acetate¼4/1).
212 mg, yield: 99%.
3.1.3. 1,1,3-Tris(3-N-methylindolyl)cyclohexane 4c. This
compound was isolated by flash chromatography to give 4c
Mp: 217–219 8C; IR (KBr) n 3470, 3401, 3054, 1456, 1418,

M. Shi et al. / Tetrahedron 60 (2004) 6679–6684
6683
as white crystals (eluent: petroleum ether/ethyl acetate¼
NH), 6.88–7.55 (15H, m, ArH); 13C NMR (CDCl3,
75 MHz): d 21.8, 28.8, 31.7, 43.6, 111.1, 111.2, 111.2,
118.8, 118.9, 119.5, 119.6, 119.62, 119.9, 120.0, 120.2,
121.5, 121.56, 121.60, 121.63, 121.68, 121.7, 122.2, 126.85,
126.87, 126.89, 136.31, 136.34, 136.4; MS (EI) m/z 403
(Mþ, 4.14), 245 (Mþ2158, 30.78), 84 (Mþ2319, 100);
HRMS (EI) calcd for C28H25N3 403.2048. Found: 403.2071
(Mþ).
4/1). 187 mg, yield: 79%.
Mp: 215–216 8C; IR (KBr): 3054, 2987, 2306, 1712, 1422,
896 cm21; 1H NMR (CDCl3, 300 MHz, TMS): d 1.54–1.69
(1H, m, CH2), 1.78–1.99 (m, 2H, CH2), 2.14–2.50 (3H, m,
CH2), 2.92–3.01 (1H, m, CH), 3.20–3.34 (2H, m, CH2),
3.63 (3H, s, NCH3), 3.72 (3H, s, NCH3), 3.86 (3H, s, NCH3),
6.67 (1H, s, ArH), 6.84 (1H, s, ArH), 6.88–7.32 (m, 10H,
ArH), 7.46 (1H, d, J¼8.0 Hz, ArH), 7.57 (1H, d, J¼8.0 Hz,
ArH), 7.71 (1H, d, J¼8.0 Hz, ArH); 13C NMR (CDCl3,
75 MHz): d 23.4, 31.0, 32.5, 32.5, 32.9, 34.3, 36.9, 40.4,
44.3, 109.0, 109.1, 109.2, 117.9, 118.1, 118.3, 118.9, 119.6,
120.7, 120.8, 121.2, 121.3, 121.3, 122.0, 124.4, 125.2,
125.7, 126.1, 127.1, 127.1, 128.0, 137.0, 137.7, 137.7; MS
(EI) m/z 471 (Mþ, 20.08), 340 (Mþ2131, 100), 144
(Mþ2327, 34.04), 131 (Mþ2340, 75.54). Anal calcd for
C33H33N3 requires C, 84.04; H, 7.05; N, 8.91. Found: C,
83.60; H, 7.20; N, 8.77%.
3.1.7. 1,1,3-Tris(3-N-methylindolyl)butane 4g. This com-
pound was isolated by flash chromatography to give 4g as a
white solid (eluent: petroleum ether/ethyl acetate¼4/1).
140 mg, yield: 63%.
Mp: 115–117 8C; IR (KBr) n 3050, 2927, 1613, 1483, 1372,
1
1326, 1013 cm21; H NMR (CDCl3, 300 MHz, TMS): d
1.41 (3H, d, J¼7.1 Hz, CH3), 2.47 (1H, dt, J¼7.4 Hz,
13.3 Hz, CH2), 2.71 (1H, dt, J¼7.4, 13.3 Hz, CH2), 3.01–
3.15 (1H, m, CH), 3.70 (6H, s, NCH3), 3.72 (3H, s, NCH3),
4.55 (1H, t, J¼7.4 Hz, CH), 6.77 (1H, s, ArH), 6.78 (1H, s,
ArH), 6.88 (1H, s, ArH), 6.92–7.04 (3H, m, ArH), 7.12–
7.30 (6H, m, ArH), 7.43 (2H, d, J¼7.8 Hz, ArH), 7.57 (1H,
d, J¼7.8 Hz, ArH); 13C NMR (CDCl3, 75 MHz): d 22.3,
29.1, 31.9, 32.6, 32.6, 44.5, 109.1, 109.2, 109.3, 118.3,
118.41, 118.42, 119.1, 119.18, 119.18, 119.86, 119.88,
119.95, 121.2, 121.28, 121.32, 121.33, 121.33, 125.2, 126.3,
126.5, 127.3, 127.6, 137.27, 137.34, 137.38; MS (EI) m/z
445 (Mþ, 15.67), 314 (Mþ2131, 10.31), 273 (Mþ2172,
100), 159 (Mþ2286, 37.89); HRMS (MALDI) calcd for
C31H31N3þNa 468.2416. Found: 468.2410.
3.1.4. 1,1,3-Tris(3-indolyl)propane 4d. This compound
was isolated by flash chromatography to give 4d as a
white powder (eluent: petroleum ether/ethyl acetate¼4/1).
103 mg, yield: 53%.
1
IR (KBr) n 3050, 2920, 2861, 1461, 1260 cm21; H NMR
(CDCl3, 300 MHz, TMS): d 2.61 (2H, q, J¼7.3 Hz, CH2),
2.85 (2H, t, J¼7.3 Hz, CH2), 4.56 (1H, t, J¼7.3 Hz, CH),
6.80–7.33 (12H, m, ArH), 7.49–7.55 (3H, m, ArH), 7.76
(3H, s, NH); MS (EI) m/z 389 (Mþ, 24.59), 258 (Mþ2131,
48.24), 245 (Mþ2144, 100); HRMS (EI) calcd for
C27H23N3 requires 389.1892. Found: 389.1852.
3.1.8. 1,1,3-Tris(3-indolyl)-3-phenylpropane 4h. This
compound was isolated by flash chromatography to give
4h as a white powder (eluent: petroleum ether/ethyl
acetate¼4/1). 186 mg, yield: 80%.
3.1.5. 1,1,3-Tris(3-N-methylindolyl)propane 4e. This
compound was isolated by flash chromatography to give
4e as a white solid (eluent: petroleum ether/ethyl acetate¼
4/1). 42 mg, yield: 20%.
Mp: 208–210 8C; IR (KBr) n 3044, 2920, 2844, 1469,
1
1257 cm21; H NMR (CDCl3, 300 MHz, TMS): d 2.80–
Mp: 111–113 8C; IR (CHCl3) n 3042, 2914, 1604, 1483,
1352, 1328, 1007 cm21 1H NMR (CDCl3, 300 MHz,
;
2.96 (1H, m, CH2), 2.99–3.11 (1H, m, CH2), 4.24 (1H, dd,
J¼10.0, 6.9 Hz, CH), 4.43 (1H, dd, J¼10.0, 6.9 Hz, CH),
6.81 (1H, d, J¼2.6 Hz, ArH), 6.88–7.35 (18H, m, ArH),
7.41 (1H, d, J¼8.4 Hz, ArH), 7.70 (1H, s, NH), 7.88 (1H, s,
NH), 7.90 (1H, s, NH); MS (EI) m/z 465 (Mþ, 2.41), 245
(Mþ2220, 100), 207 (Mþ2248, 60.18). Anal. calcd for
C33H27N3 requires C, 85.13; H, 5.85; N, 9.03. Found: C,
84.86; H, 5.85; N, 8.92%.
TMS): d 2.57–2.67 (2H, m, CH2), 2.80–2.89 (2H, m,
CH2), 3.71 (3H, s, NCH3), 3.72 (6H, s, NCH3), 4.57 (1H, t,
J¼7.4 Hz, CH), 6.78 (1H, s, ArH), 6.88 (2H, s, ArH), 6.98–
7.07 (3H, m, ArH), 7.14–7.30 (6H, m, ArH), 7.50 (1H, d,
J¼7.8 Hz, ArH), 7.57 (2H, d, J¼7.8 Hz, ArH); 13C NMR
(CDCl3, 75 MHz): d 23.8, 32.5, 32.6, 33.6, 36.6, 109.0,
109.0, 115.3, 118.3, 118.4, 118.9, 119.2, 119.8, 121.2,
121.3, 126.0, 126.3, 127.5, 127.9, 137.0, 137.2; MS (EI) m/z
431 (Mþ, 6.11), 300 (Mþ2131, 4.91), 273 (Mþ2158,
62.20), 144 (Mþ2287, 100), 131 (Mþ2300, 56.68); HRMS
(MALDI) calcd for C30H29N3þNa 454.2259. Found:
454.2254.
3.1.9. 1,1,3-Tris(3-N-methylindolyl)-3-phenylpropane 4i.
This compound was isolated by flash chromatography to
give 4i as white crystals (eluent: petroleum ether/ethyl
acetate¼4/1). 39 mg, yield: 15%.
Mp: 222–224 8C; IR (KBr): n 3052, 2931, 1614, 1484,
1471, 1155, 1013, 1327 cm21; 1H NMR (CDCl3, 300 MHz,
TMS): d 2.84–2.95 (1H, m, CH2), 2.98–3.09 (1H, m, CH2),
3.65 (3H, s, NCH3), 3.73 (3H, s, NCH3), 3.76 (3H, s, NCH3),
4.25 (1H, dd, J¼9.4, 6.1 Hz, CH), 4.41 (1H, dd, J¼9.4,
6.1 Hz, CH), 6.72 (1H, s, ArH), 6.88–7.01 (5H, m, ArH),
7.11–7.34 (13H, m, ArH), 7.43 (1H, dd, J¼8.0, 0.9 Hz,
ArH); 13C NMR (CDCl3, 75 MHz): d 31.3, 32.6, 32.63,
32.7, 40.6, 42.7, 108.9, 109.00, 109.01, 118.0, 118.3,
118.35, 118.43, 118.43, 119.0, 119.43, 119.56, 119.56,
119.8, 120.0, 120.0, 121.19, 121.27, 121.37, 125.88, 125.93,
3.1.6. 1,1,3-Tris(3-indolyl)butane 4f. This compound was
isolated by flash chromatography to give 4f as a white solid
(eluent: petroleum ether/ethyl acetate¼4/1). 123 mg, yield:
61%.
Mp: 108–110 8C; IR (KBr) n 3056, 2925, 2851, 1460,
1269 cm21; 1H NMR (CDCl3, 300 MHz, TMS): d 1.34 (3H,
d, J¼6.9 Hz, CH3), 2.31–2.43 (1H, m, CH2), 2.54–2.67
(1H, m, CH2), 2.91–3.30 (1H, m, CH), 4.46 (1H, t, J¼
7.7 Hz, CH), 6.54 (1H, s, NH), 6.59 (1H, s, NH), 6.65 (1H, s,

6684
M. Shi et al. / Tetrahedron 60 (2004) 6679–6684
126.28, 126.41, 127.2, 128.21, 128.23, 137.14, 137.31,
145.4; MS (EI) m/z 507 (Mþ, 15.46), 376 (Mþ2131, 49.35),
273 (Mþ2234, 100), 245 (Mþ2262, 4.29), 221 (Mþ2286,
35.92), 144 (Mþ2363, 10.75). Anal calcd for C36H33N3
requires C, 85.17; H, 6.55; N, 8.28. Found: C, 84.88; H,
6.51; N, 8.21%.
100). Anal. calcd for C28H25N3 requires C, 83.34; H, 6.29;
N, 10.41. Found: C, 83.31; H, 6.19; N, 10.27%.
Acknowledgements
We thank the State Key Project of Basic Research (Project
973) (No. G2000048007), Chinese Academy of Sciences
(KGCX2-210-01), Shanghai Municipal Committee of
Science and Technology, and the National Natural Science
Foundation of China for financial support (20025206,
20390050, and 20272069).
3.1.10. [3,3-Bis(3-N-methylindolyl)propenyl]benzene 4j.
This compound was isolated by flash chromatography to
give 4j as colorless crystals (eluent: petroleum ether/ethyl
acetate¼10/1). 52 mg, yield: 28%.
Mp: 167–169 8C; IR (KBr) n 3054, 2929, 2306, 1613, 1469,
1422, 909 cm21; 1H NMR (CDCl3, 300 MHz, TMS): d 3.67
(1H, s, CH), 3.71 (6H, s, NCH3), 5.39 (1H, d, J¼7.1 Hz,
CH), 6.49–6.56 (1H, m, CH), 6.74–6.82 (2H, m, ArH),
7.00–7.07 (2H, m, ArH), 7.14–7.38 (9H, m, ArH), 7.60
(2H, d, J¼6.9 Hz, ArH); 13C NMR (CDCl3, 75 MHz): d
32.7, 37.3, 109.1, 116.9, 118.7, 120.1, 121.4, 126.3, 126.9,
127.3, 127.34, 128.4, 129.6, 132.8, 137.4, 137.8; MS (EI)
m/z 376 (Mþ, 100), 299 (Mþ277, 13.05), 273 (Mþ2103,
46.55), 144 (Mþ2232, 25.47), 77 (Mþ2299, 9.24). Anal
calcd for C36H33N3 requires C, 86.13; H, 6.43; N, 7.44.
Found: C, 86.33; H, 6.41; N, 7.43%.
References and notes
1. Bull, S. D.; Davies, S. G.; Delgado-Ballester, S.; Fenton, G.;
Kelly, P. M.; Smith, A. D. Synlett 2000, 1257–1258. (b) Davies,
S. G.; McCarthy, T. D. Synlett 1995, 700–701. (c) Rosenthal,
D.; Braundrup, G.; Davis, K. H.; Wall, M. E. J. Org. Chem.
1965, 30, 3689–3693. (d) Pushechnikov, O.; Ivonin, S. P.;
Chaikovskaya, A. A.; Kudrya, T. N. Chem. Heterocycl. Compd.
1999, 35, 1313–1318.
3.1.11. 1,1,3-Tris(2-pyrolyl)cyclohexane 4k. This com-
pound was isolated by flash chromatography to give 4k as a
yellowish oil (eluent: petroleum ether/ethyl acetate¼4/1).
56 mg, yield: 40%.
2. Harrington, P. E.; Kerr, M. A. Can. J. Chem. 1998, 76,
1256–1265. (b) Kotsuki, H.; Teraguchi, M.; Shimomoto, N.;
Ochi, M. Tetrahedron Lett. 2002, 43, 4075–4078.
(c) Harrington, P. E.; Kerr, M. A. Synlett 1996, 1047–1048.
(d) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68,
2109–2117. (e) Chakrabarty, M.; Ghosh, N.; Basak, R.;
Harigaya, Y. Tetrahedron Lett. 2002, 43, 4075–4078.
(f) Banerji, J.; Dutta, U.; Basak, B.; Saha, M.; Budzikiewicz,
H.; Chatterjee, A. Indian. Chem. Sect., B 2001, 40, 981–984.
(g) Yadav, J. S.; Reddy, B. V.; Subba, M. Ch. V. S. R.; Kumar,
G. M.; Madan, C. Synthesis 2001, 5, 783–787.
Mp: 189–191 8C; IR (KBr) n 3043, 2921, 2866, 1478,
1258 cm21 1H NMR (CD3COCD3, 300 MHz, TMS): d
;
1.55–1.77 (2H, m, CH2), 1.78–2.01 (4H, m, CH2), 2.58
(1H, d, J¼13.7 Hz, CH), 2.74–2.91 (2H, m, CH2), 5.69–
6.17 (6H, m, ArH), 6.49–6.72 (3H, m, ArH), 9.32 (1H, s,
NH), 9.83 (1H, s, NH), 9.94 (1H, s, NH); MS (EI) m/z 279
(Mþ, 100), 212 (Mþ267, 58.54), 145 (Mþ2134, 36.61);
HRMS (EI) calcd for C18H21N3 requires 279.1735. Found:
279.1741.
3. These cytotoxic compounds are a class of at least 20 members
isolated from the blue-green algae Hapalosiphon fontinalis
by Moore and co-workers. (a) Moore, R. E.; Cheuk, C.; Yang,
X.-Q.; Patterson, G. M. L.; Bonjouklian, R.; Smitka, T. A.;
Mynderse, J.; Foster, R. S.; Jones, N. D.; Swartzendruber, J. K.;
Deeter, J. B. J. Org. Chem. 1987, 52, 1036–1041. (b) Moore,
R. E.; Cheuk, C.; Patterson, G. M. L. J. Am. Chem. Soc. 1984,
106, 6456–6457.
3.1.12. 2,2,4-Tris(3-indolyl)butane 4l. This compound was
isolated by flash chromatography to give 4l as s white solid
(eluent: petroleum ether/ethyl acetate¼4/1). 16 mg, yield:
8%.
4. Wang and co-workers reported the 1,2-addition of indole to
cyclohexanone accompanied with dehydration to give a two
indole-incorporated product Chen, D.; Yu, L.; Wang, P. G.
Tetrahedron Lett. 1996, 37, 4467–4470.
Mp: 155–157 8C; IR (KBr) n 3053, 2926, 2854, 1465,
1265 cm21; 1H NMR (CDCl3, 300 MHz, TMS): d 2.00 (3H,
s, CH3), 2.60 (2H, t, J¼8.6 Hz, CH2), 2.80 (2H, t, J¼8.6 Hz,
CH2), 6.81–7.18 (9H, m, ArH), 7.31 (4H, t, J¼7.3 Hz,
ArH), 7.41 (2H, d, J¼8.4 Hz, ArH), 7.84 (1H, s, NH), 7.97
(2H, s, NH); MS (EI) m/z 403 (Mþ, 15.08), 259 (Mþ2144,
5. Kerr reported that under ultra high pressure (13 kbar)
trisindolylcyclohexane was formed in 6% in the reaction of
1-methylindole with 3-methyl-2-cyclohexene-1-one2a.