Short approach to bisindole alkaloid, yuehchukene, using 2-indolylcyanocuprate

Article abstract of DOI:10.3987/COM-12-S(N)49

A short total synthesis of a bisindole alkaloid, yuechukene, was achieved through the dimerization of β-dehydroprenylindole generated in situ from 1-(indol-3-yl)-3-methylbut-2-en-1-amine.

Full text of DOI:10.3987/COM-12-S(N)49

HETEROCYCLES, Vol. 86, No. 1, 2012
505
HETEROCYCLES, Vol. 86, No. 1, 2012, pp. 505 - 513. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 22nd June, 2012, Accepted, 2nd August, 2012, Published online, 13th August, 2012
DOI: 10.3987/COM-12-S(N)49
SHORT APPROACH TO BISINDOLE ALKALOID, YUEHCHUKENE,
USING 2-INDOLYLCYANOCUPRATE
Takumi Abe, Hiroyuki Komatsu, Toshiaki Ikeda, Noriyuki Hatae, Eiko
Toyota, and Minoru Ishikura*
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293, Japan. E-mail: ishikura@hoku-iryo-u.ac.jp
Abstract – A short total synthesis of a bisindole alkaloid, yuechukene, was
achieved through the dimerization of -dehydroprenylindole generated in situ
from 1-(indol-3-yl)-3-methylbut-2-en-1-amine.
INTRODUCTION
A novel bisindole alkaloid, yuehchukene (1), was first isolated from the root of Murraya paniculata (L.)
Jack in racemic form, and the structure was characterized as a dimer of -dehydroprenylindole (2) based
on both spectral analysis and X-ray crystallography (Figure 1).1 Yuehchukene (1) exhibits strong
anti-implantation activity in rats as well as mice.2 Additionally, a combination of cyclophosphamide and
1 provides a fairly strong cytotoxic effect on the MCR-7 cell line when compared with cyclophosphamide
alone.3 Owing to the potential biological activities of 1, it is an attractive target for synthesis.4 We
previously reported the total synthesis of 1 with the key step being a palladium-catalyzed carbonylative
cross-coupling reaction of triethyl(indol-2-yl)borate.5 The hypothesis6 that 1 is the biogenetic product of
the dimerization of 2 has prompted the development of biomimetic approach using
1-(indol-3-yl)-3-methylbut-2-en-1-ol or 4-(indol-3-yl)-2-methylbut-3-en-2-ol as the key precursor of 2
under neutral conitions or acid catalysis.7 In connection with our continuing interest in synthetic
application of 2-indolylcyanocuprate 4, we previously reported the regioselective construction of
2,3-disubstituted indoles through the reaction of 2-indolylcyanocuprate 4 with electrophiles in a one-pot
procedure.8 It was envisioned that 1-(indol-3-yl)-3-methylbut-2-en-1-amine 7, regioselectively obtainable
by the reaction of 4 with iminium 6,8a could serve as a useful synthetic equivalent of 2.9 In this paper, we
describe a short total synthesis of yuehchukene (1) through the dimerization of 7.
This paper is dedicated to Prof. Ei-ichi Negishi on the occasion of his 77th birthday.

506
HETEROCYCLES, Vol. 86, No. 1, 2012
RESULTS AND DISCUSSION
Me
Me
H
Me
Me
H
N
H
N
H
NH
1
2
yuehchukene ( )
Figure 1. Yuehchukene (1) and -dehydroprenylindole (2)
Our initial attempts to obtain the 3-substituted indole 7 through the reaction of 6 (derived from imine 5
and ClCO2Ph) with indole or indolyl anion (generated by treating indole with NaH in THF) were
unsuccessful, resulting in only the recovery of indole or the formation of a complex mixture of products.
As a result, the reaction of 4 (generated in situ from indole 3 and tert- or n-BuLi in THF, followed by
treatment with CuCN at -20 °C) with iminium 6 was undertaken by way of a one-pot procedure.8a The
reaction was carried out through slow addition of an acyl chloride to a pre-mixed solution of 4 and 5 in
THF in the presence of HMPA at -20 °C, resulting in the formation of two types of products 1,2-adduct 7
and 1,4-adduct 8 (Scheme 1 and Table 1).10 After screening various acyl chlorides (X-Cl), in the reaction
of 4a with 5, ClCO2Ph was found to give 7d in the highest yield (65%) along with 8d in 14% yield (Entry
4). Furthermore, reacting 4b with 5 by adding ClCO2Ph afforded 7e in 60% and 8e in 12% yields (Entry
6). However, performing the reaction of 4a with 5 in the presence of i-Pr2NEt and HMPA using ClCO2Ph
at -20 °C lowered the yield of 7d to 30% (Entry 5). This was ascribed to the facile generation of
dienamine 9 from 6 (X = CO2Ph) via deprotonation/isomerization, which was enhanced by the presence
of i-Pr2NEt.8a No reaction was observed between 4c and 5 when using ClCO2Ph (Entry 7).
H
Bn
N
Me
Me
X
Bn
N
Me
Me
Me
Bn
1)
Me
N
1) or t
BuLi
n-
ert-
Li+
5
THF
X
-
+
CuCN
N
R
N
R
THF
conditions (Table 1)
2) CuCN, -20 °C
N
N
R
3
a
4
R
8
2)
7
Cl-X
a
: R = Me
: R = Me
b
b
: R = OMe
: R = OMe
Cl-
c
c
: R = Boc
: R = Boc
PhO2C
Bn
X
H
+
N
N
Me
Me
Bn
Me
9
6
Scheme 1

HETEROCYCLES, Vol. 86, No. 1, 2012
507
Table 1. Reaction of 4 with 5 using acyl chloride (X-Cl)
Yield (%)a
Entry
R
X-Cl
Conditions
7
8
1
2
3
4
5
6
7
Me
Me
ClCOMe
ClCOPh
HMPA / -20 °C to rt
HMPA / -20 °C to rt
48 (7a)
50 (7b)
45 (7c)
65 (7d)
30 (7d)
60 (7e)
----
17 (8a)
13 (8b)
13 (8c)
14 (8d)
5 (8d)
12 (8e)
----
Me
ClCO2Me
ClCO2Ph
ClCO2Ph
ClCO2Ph
ClCO2Ph
HMPA / -20 °C to rt
Me
HMPA / -20 °C to rt
HMPA / i-Pr2NEt / -20 °C to rtb
Me
OMe
Boc
HMPA / -20 °C to rt
HMPA / -20 °C to rt
aIsolated yield based on 3. bi-Pr2NEt (3 equiv).
Next, we turned our attention to the dimerization of 7d (Table 2). Initially, 7d was simply heated in
ethylene glycol at 150 °C, but no isolable products were obtained (Entry 1). Heating 7d in the presence of
2 equiv of TFA and AcOH in ethylene glycol at 150 °C resulted in the formation of a complex mixture of
products (Entries 2 and 3), whereas treating 7d with TMSCl (2 equiv) in CH2Cl2 at room temperature
produced N,N’-dimethylyuehchukene 13, but in only low yield (~10%) (Entry 6). After performing the
dimerization reaction under various conditions, using TMSCl (2 equiv) in DME in pre-heated oil bath at
100 °C was found to provide 13 in 20% yield (Entry 7). The highest yield of 13 (35%) was obtained
through the slow addition of a DME solution of TMSCl (1 equiv) to a refluxing solution of 7d in DME
(Entry 8).
Me
Me
Me
Bn
N
Me
PhO2C
H
H
Me
Me
Me
Me
Me
Me
Me
H
H
+
N
Me
N
N
conditions
(Table 2)
Me
Me
N
+
N
Me
N
Me
N
Me
Me
11
7d
12
10
13
Scheme 2
The dimerization reaction is presumed to proceed by the in situ generation of diene 10 and its dienophilic
tautomer 11 from 7d, the subsequent Diels-Alder reaction between 10 and 11, followed by the
intramolecular cyclization of 12 to 13 (Scheme 2).6

508
HETEROCYCLES, Vol. 86, No. 1, 2012
Table 2. Conversion of 7d to N,N’-dimethylyuehchukene (13)
Entry
Conditions
(CH2OH)2 / 150 °C/ 24 h
Yield (%)a
-----
-----
-----
-----
10
1
2
3
4
5
6
7
8
(CH2OH)2 / TFA (2 equiv) / 150 °C/ 24 h
(CH2OH)2 / AcOH (2 equiv) / 150 °C/ 24 h
(CH2OH)2 / TMSCl (2 equiv) / 150 °C/ 3 h
CH2Cl2 / TMSCl (2 equiv) / rt / 16 h
CH2Cl2 / TMSCl (0.1 equiv) / rt / 16 h
DME / TMSCl (2 equiv) / 100 °C / 6 hb
DME / TMSCl (1 equiv) / 100 °C / 16 hc
----
20
35
aIsolated yield based on 3a. bPre-heated oil bath at 100 °C. cThe reaction was
performed by adding a DME solution of TMSCl to a refluxing solution of 7d in DME.
After having found suitable conditions for the dimerization of 7d, 7e was subjected to the dimerization in
a similar manner. After a solution of TMSCl (1 equiv) was added dropwise to a solution of 7e at 100 °C,
the mixture was heated at 100 °C for an additional 16 h, producing yuehchukene (1) in 30% yield
(Scheme 3).11
Me
Bn
Me
PhO2C
H
N
Me
Me
Me
TMSCl (1 equiv)
H
N
H
N
DME, 100 °C, 16 h
7e
OMe
1
NH
30%
Scheme 3
In summary, we have developed a short total synthesis of N,N’-dimethylyuehchukene (13) and
yuehchukene (1) from the corresponding indoles 3a and 3b via 2-indolylcyanocuprates 4a and 4b. We are
currently investigating further application of 2-indolylcyanocuprates 4 in the synthesis of other indole
alkaloids.
EXPERIMENTAL
Melting points were recorded on a Yamato MP21 and are uncorrected. HR-ESI-MS spectra were recorded
on a JEOL JMS-T100LP mass spectrometer, and HR-EI-MS spectra were recorded on a Micromass

HETEROCYCLES, Vol. 86, No. 1, 2012
509
AutoSpec 3100 mass spectrometer. IR spectra were measured on a Shimadzu IRAffinity-1 FT-IR
spectrophotometer. The NMR experiments were performed with a JEOL JNM-ECA500 (500 MHz)
spectrometer, and chemical shifts are expressed in ppm () with TMS as an internal reference. Column
chromatography was performed on silica gel (Silica Gel 60N, Kanto Chemical Co., Ltd.).
General procedure for the reaction of 4a with 5 using acyl chloride (X-Cl): tert-BuLi (1.6 M in
pentane, 1.5 mL, 2.4 mmol) was added to a solution of 1-methylindole (3a) (262 mg, 2 mmol) in THF (30
mL) at 0 °C under an argon atmosphere, and the mixture was stirred at room temperature for 1 h. After
the mixture was cooled to -20 °C, CuCN (214 mg, 2.4 mmol) was added to the mixture at -20 °C, and the
mixture was stirred for 30 min. After HMPA (1 mL) and imine 5 (519 mg, 3 mmol) were added, acyl
chloride (X-Cl) (3 mmol) was added slowly to the mixture. The reaction mixture was gradually warmed
to room temperature and stirred overnight. The mixture was diluted with AcOEt (200 mL), washed with
brine and dried over MgSO4. The solvent was removed, and the residue was separated by silica gel
column chromatography with hexane/AcOEt (15:1) to give 7 and 8 (Table 1).
N-Benzyl-N-[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]acetamide (7a): IR (CHCl3): 1622
cm–1. 1H-NMR (CDCl3) : 1.70 (s, 3H), 1.85 (s, 3H), 1.99 (s, 3H), 3.74 (s, 3H), 4.33 (d, 1H, J = 17.8 Hz),
4.41 (d, 1H, J = 18.4 Hz), 5.45 (d, 1H, J = 9.8 Hz), 6.90 (s, 1H), 7.04–7.29 (m, 9H), 7.66 (d, 1H, J = 8.0
Hz). 13C-NMR (CDCl3) : 18.9, 22.6, 25.8, 32.9, 48.1, 48.2, 109.3, 114.6, 119.6, 120.1, 122.0, 122.1,
126.1, 126.8, 127.8, 127.9, 128.2, 128.4, 136.4, 137.5, 139.0, 170.1. HR-EI-MS m/z: Calcd for
C23H26N2O (M+): 346.2045. Found: 346.2045.
N-Benzyl-N-[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]acetamide (8a): IR (CHCl3):
1638 cm–1. 1H-NMR (CDCl3) : 1.45 (s, 3H), 1.56 (s, 3H), 2.10 (s, 3H), 3.66 (s, 3H), 4.89 (s, 2H), 5.38 (d,
1H, J = 14.4 Hz), 6.44 (d, 1H, J = 14.4 Hz), 7.02 (d, 1H, J = 8.0 Hz), 7.14–7.31 (m, 8H), 7.51 (d, 1H, J =
8.0 Hz). 13C-NMR (CDCl3) : 22.2, 29.1, 29.5, 32.6, 36.0, 46.5, 109.4, 118.5, 121.3, 121.4, 122.3, 124.8,
125.4, 125.9, 127.0, 127.3, 128.5, 128.9, 137.5, 137.8, 169.8. HR-EI-MS m/z: Calcd for C23H26N2O (M+):
346.2045. Found: 346.2041.
N-Benzyl-N-[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]benzamide (7b): IR (CHCl3): 1620
cm–1. 1H-NMR (CDCl3) : 1.71 (s, 3H), 1.82 (s, 3H), 3.60 (s, 3H), 4.46 (s, 1H), 4.49 (s, 1H), 5.33 (d, 1H,
J = 14.9 Hz), 5.56 (br s, 1H), 6.40 (br s, 1H), 7.00–7.45 (m, 13H), 7.71 (br s, 1H). 13C-NMR (CDCl3) :
19.6, 25.6, 42.4, 47.9, 50.2, 112.4, 117.6, 119.0, 126.5, 127.1, 127.2, 128.0, 128.6, 131.9, 135.2, 136.5,
169.5. HR-EI-MS m/z: Calcd for C28H28N2O (M+): 408.2202. Found: 408.2199.
N-Benzyl-N-[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]benzamide (8b): IR (CHCl3):
1638 cm–1. 1H-NMR (CDCl3) : 1.49 (s, 6H), 3.65 (s, 3H), 4.80 (s, 2H), 5.13 (d, 1H, J = 14.4 Hz), 6.35 (d,
13
1H, J = 14.4 Hz), 7.05 (d, 1H, J = 8.0 Hz), 7.15-7.37 (m, 13H), 7.54 (d, 1H, J = 8.0 Hz). C-NMR

510
HETEROCYCLES, Vol. 86, No. 1, 2012
(CDCl3) : 32.1, 32.3, 42.4, 48.4, 49.3, 111.1, 116.2, 119.0, 120.1, 122.2, 122.3, 126.3, 126.5, 126.6,
126.8, 127.0, 127.1, 127.5, 127.8, 128.5, 128.6, 128.9, 132.2, 134.2, 137.6, 141.7, 169.3. HR-EI-MS m/z:
Calcd for C23H26N2O (M+): 346.2045. Found: 346.2041.
Methyl Benzyl[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]carbamate (7c): IR (CHCl3): 1680
1
cm–1. H-NMR (CDCl3) : 1.68 (s, 3H), 1.75 (s, 3H), 3.74 (s, 3H), 3.78 (br s, 3H), 4.15 (s, 1H), 4.18 (s,
1H), 4.51 (br s, 1H), 5.46 (d, 1H, J = 9.2 Hz), 6.52 (br s, 1H), 6.87 (br s, 1H), 7.06–7.30 (m, 8H), 7.62 (br
13
s, 1H). C-NMR (CDCl3) : 14.3, 18.5, 25.8, 32.9, 47.0, 51.4, 52.8, 60.5, 109.3, 114.4, 119.5, 119.9,
122.1, 122.9, 126.4, 127.1, 128.0, 135.5, 137.5, 140.0, 157.3. HR-EI-MS m/z: Calcd for C23H26N2O2
(M+): 362.1994. Found: 362.1989.
Methyl Benzyl[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]carbamate (8c): IR (CHCl3):
1686 cm–1. 1H-NMR (CDCl3) : 1.41 (s, 6H), 3.65 (s, 3H), 3.71 (br s, 3H), 4.82 (br d, 2H, J = 12.1 Hz),
5.27 (d, 1H, J = 14.9 Hz), 6.60, 6.65(two br s, 1H), 6.89–7.31(m, 9H), 7.49 (d, 1H, J = 8.0 Hz). 13C-NMR
(CDCl3) : 18.9, 22.6, 25.8, 32.9, 48.1, 48.2, 109.3, 114.6, 119.6, 120.1, 122.0, 122.1, 126.1, 126.8, 127.8,
127.9, 128.2, 128.4, 136.4, 137.5, 139.0, 170.1. HR-EI-MS m/z: Calcd for C28H26N2O2 (M+): 362.1994.
Found: 362.1989.
Phenyl Benzyl[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]carbamate (7d): IR (CHCl3): 1702
cm–1. 1H-NMR (CDCl3) : 1.71 (s, 3H), 1.77 (s, 3H), 3.76 (s, 3H), 4.31 (m, 1H), 4.61 (d, 1H, J = 16.1 Hz),
5.56 (d, 1H, J = 8.6 Hz), 6.58 (br s, 1H), 6.90–7.41 (m, 14H), 7.73 (br s, 1H). 13C-NMR (CDCl3) : 18.6,
25.8, 32.9, 47.4, 51.6, 109.4, 114.1, 119.6, 119.9, 121.9, 122.1, 125.2, 126.6, 127.1, 128.1, 129.3, 136.3,
137.5, 139.7, 151.6, 155.1. HR-EI-MS m/z: Calcd for C28H28N2O2 (M+): 424.2151. Found: 424.2149.
Phenyl Benzyl[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]carbamate (8d): IR (CHCl3):
1
1716 cm–1. H-NMR (CDCl3) : 1.51 (s, 6H), 3.65 (s, 3H), 4.91, 4.95 (two s, 2H), 5.40 (d, 1H, J = 15.0
Hz) 6.42, 6.52 (two s, 1H), 7.00–7.43 (m, 14H), 7.61 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) : 29.2, 32.6,
35.8, 48.4, 109.4, 118.5, 121.2, 121.3, 121.8, 121.9, 123.0, 123.2, 124.2, 125.0, 125.1, 125.7, 126.6, 127.2,
127.3, 128.7, 129.4, 137.2, 137.8, 151.2, 151.4, 153.3. HR-EI-MS m/z: Calcd for C28H28N2O2 (M+):
424.2151. Found: 424.2145.
Reaction of 4b with 5 using ClCO2Ph: n-BuLi (1.6 M in hexane, 1.5 mL, 2.4 mmol) was added to a
solution of 1-methoxyindole (3b) (294 mg, 2 mmol) in THF (30 mL) at -20 °C under an argon
atmosphere, and the mixture was stirred for 30 min. Then, CuCN (214 mg, 2.4 mmol) was added to the
mixture at -20 °C and the whole was stirred for 30 min. After HMPA (1 mL) and imine 5 (519 mg, 3
mmol) were added to the mixture at -20 °C, ClCO2Ph (468 mg, 3 mmol) was added slowly. The mixture
was gradually warmed to room temperature and stirred overnight. The mixture was diluted with AcOEt
(200 mL), washed with brine and dried over MgSO4. After the solvent was removed, the residue was

HETEROCYCLES, Vol. 86, No. 1, 2012
511
separated by silica gel column chromatography with hexane/AcOEt (15:1) to give 7e and 8e (Table 1).
Phenyl Benzyl[1-(1-methoxy-1H-indol-3-yl)-3-methylbut-2-en-1-yl]carbamate (7e): a pale yellow oil.
IR (neat): 1714, 1699, 1595 cm-1. 1H-NMR (CDCl3) : 1.72, 1.77 (two s, 6H), 4.04 (s, 3H), 4.32 (d, 1H, J
= 15.0 Hz), 4.60 (d, 1H, J = 15.0 Hz), 5.53 (d, 1H, J = 9 Hz), 6.43-6.62 (m, 0.5 H), 6.90-7.05 (m, 1H),
7.10-7.23 (m, 10H), 7.23-7.39 (m, 3H), 7.41 (d, 1H, J = 9 Hz), 7.60-7.76 (m, 0.5H). 13C-NMR (CDCl3) :
18.6, 25.8, 47.4, 51.3, 65.9, 108.4, 111.5, 120.1, 120.3, 121.8, 122.4, 122.9, 125.3, 126.6, 126.8, 128.1,
129.3, 132.8, 136.9, 139.4, 151.5, 155.0. HR-ESI-MS m/z: Calcd for C28H28N2O3Na [(M+Na)+]:
463.1998. Found: 463.2008.
Phenyl Benzyl[(1E)-3-(1-methoxy-1H-indol-3-yl)-3-methylbut-1-en-1-yl]carbamate (8e): a pale
yellow oil. IR (neat): 1714, 1660 cm-1. 1H-NMR (CDCl3) : 1.48, 1.54 (two s, 6H), 4.00 (s, 3H), 4.90 (s,
1H), 4.93 (s, 1H), 5.36 (d, 1H, J = 14.8 Hz), 6.66, 6.75 (two s, 1H), 6.90-7.09 (m, 2H), 7.10-7.24 (m, 2H),
13
7.30-7.40 (m, 10H) 7.56 (d, 1H, J = 7.3 Hz). C-NMR (CDCl3) : 29.1, 35.9, 48.4, 65.5, 108.4, 119.2,
119.4, 119.5, 120.6, 120.8, 121.4, 121.7, 122.0, 122.1, 122.2, 122.5, 122.7, 124.4, 125.2, 125.7, 126.5,
127.2, 127.3, 128.7, 129.4, 133.5, 137.1, 151.1, 151.3, 153.2, 153.3. HR-ESI-MS m/z: Calcd for
C28H28N2O3Na [(M+Na)+]: 463.1998. Found: 463.1996.
N,N’-Dimethylyuehchukene (13): To a solution of 7d (110 mg, 0.26 mmol) in DME (30 mL) at 100 °C
under an argon atmosphere, a solution of TMSCl (33 L, 0.26 mmol) in DME (100 L) was added
dropwise over 10 min, and the mixture was heated at 100 °C for 16 h. After cooling, the mixture was
diluted with AcOEt (200 mL), washed with 10% aq. NaHCO3 solution and brine, and dried over MgSO4.
The solvent was removed and the residue was separated by silica gel column chromatography with
hexane/AcOEt (7:1) to give 13 (35 mg, 35%) as a pale yellow oil. IR (CHCl3): 3007, 2957, 2928 cm-1.
1H-NMR (CDCl3) : 0.83 (s, 3H), 1.08 (s, 3H), 1.62 (d, 1H, J = 17.2 Hz), 1.64 (s, 3H), 2.19 (d, 1H, J =
17.2 Hz), 3.06 (t, 1H, J = 6.9 Hz), 3.11 (s, 3H), 3.76 (s, 3H), 4.02 (d, 1H, J = 4.6 Hz), 4.56 (d, 1H, J = 7.5
Hz), 5.71 (s, 1H), 6.88 (s, 1H), 7.00 (t, 1H, J = 7.4 Hz), 7.07-7.10 (m, 2H), 7.13 (m, 1H), 7.20 (t, 1H, J =
13
7.5 Hz), 7.29 (d, 1H, J = 8.6 Hz), 7.40 (d, 1H, J = 8.1 Hz), 7.58 (dd, 1H, J = 3.4, 6.3 Hz). C-NMR
(CDCl3) : 24.2, 28.5, 29.2, 29.9, 32.8, 33.6, 37.2, 38.4, 41.5, 62.5, 109.3, 109.5, 117.7, 118.4, 118.9,
119.0, 119.3, 119.6, 119.9, 121.5, 123.1, 123.5, 127.2, 127.3, 130.3, 137.2, 141.2, 146.3. HR-ESI-MS
m/z: Calcd for C28H31N2 [(M+H)+]: 395.248. Found: 395.2481.
Yuehchukene (1): To a solution of 7e (125 mg, 0.28 mmol) in DME (30 mL) at 100 °C under an argon
atmosphere, a solution of TMSCl (36 L, 0.28 mmol) in DME (100 L) was added dropwise over 10 min,
and the mixture was heated at 100 °C for 16 h. After cooling, the mixture was diluted with AcOEt (200
mL), washed with 10% aq. NaHCO3 solution and brine, and dried over MgSO4. The solvent was removed
and the residue was separated by silica gel column chromatography with hexane/AcOEt (4:1) to give 1

512
HETEROCYCLES, Vol. 86, No. 1, 2012
1
(31 mg, 30%) as amorphous powders. IR (CHCl3): 3476, 3422, 3009 cm-1. H-NMR (CDCl3) : 0.86 (s,
3H), 1.09 (s, 3H), 1.62 (d, 1H, J = 17.7 Hz), 1.66 (s, 3H), 2.28 (d, 1H, J = 17.7 Hz), 3.16 (t, 1H, J = 7.5
Hz), 4.02 (d, 1H, J = 5.0 Hz), 4.56 (d, 1H, J = 8.5 Hz), 5.70 (s, 1H), 6.99-7.06 (m, 3H), 7.07-7.12 (m, 2H),
7.18 (t, 1H, J = 8.5 Hz), 7.34 (d, 1H, J = 7.5 Hz), 7.43 (d, 1H, J = 8.0 Hz), 7.46 (br s, 1H), 7.58 (d, 1H, J
= 8.0 Hz), 8.03 (br s, 1H). 13C-NMR (CDCl3) : 24.2, 29.0, 29.2, 33.6, 37.7, 38.4, 41.1, 60.9, 111.4, 111.8,
118.4, 118.5, 119.4, 119.6, 120.5, 120.6, 122.1, 122.5, 123.1, 124.3, 126.9, 130.3, 136.5, 140.3, 145.3.
HR-ESI-MS: Calcd for C26H27N2 [(M+H)+]: 367.2174. Found: 367.2167.
ACKNOWLEDGEMENTS
This work was supported in part by the Ministry of Education, Culture, Sports, Sciences and Technology
of Japan through a Grant-in Aid for Scientific Research (No. 22590010 for M. I. and No. 23590143 for N.
H.).
REFERENCES AND NOTES
1. Y. C. Kong, K. F. Cheng, R. C. Cambie, and P. G. Waterman, J. Chem. Soc., Chem. Commun., 1985,
47.
2. (a) P. C. Ng, D. D. Ho, K. H. Ng, Y. C. Kong, K. F. Cheng, and G. Stone, Eur. J. Pharmacol., 1994,
264, 1; (b) K. F. Cheng, T. T. Wong, K. P. Chan, and Y. C. Kong, Eur. J. Med. Chem., 1992, 27,
121.
3. (a) T. W. T. Leung, G. Cheng, C. H. Chui, S. K. W. Ho, F. Y. Lau, J. K. J. Tjong, T. C. C. Poon, J, C.
O. Tang, W. C. P. Tse, K. F. Cheng, and Y. C. Kong, Chemotherapy, 2000, 46, 62; (b) D. C. C.
Wang, W. P. Fong, S. S. T. Lee, Y. C. Kong, K. F. Cheng, and G. Stone, Eur. J. Pharmacol., 1998,
362, 87.
4. (a) H. Naka, Y. Akagi, K. Yamada, T. Imahori, T. Kasahara, and Y. Kondo, Eur. J. Org. Chem.,
2007, 4635; (b) J. Bergman and L. Venemalm, Pure & Appl. Chem., 1994, 66, 2331; (c) K. J. Henry,
Jr. and P. A. Grieco, J. Chem. Soc., Chem. Commun., 1993, 510; (d) J. Bergman and L. Venemalm,
Tetrahedron, 1992, 48, 759; (e) J. P. Kutney, F. J. Lopez, S. P. Huang, H. Kurobe, R. Flogaus, K.
Piotrowska, and S. J. Rettig, Can. J. Chem., 1991, 69, 949; (f) J. P. Kutney, F. J. Lopez, S. P. Huang,
and H. Kurobe, Heterocycles, 1989, 28, 565; (g) J. Bergman and L. Venemalm, Tetrahedron Lett.,
1988, 29, 2993.
5. (a) M. Ishikura, K. Imaizumi, and N. Katagiri, Heterocycles, 2000, 53, 553; (b) M. Ishikura, K.
Imaizumi, and N. Katagiri, Heterocycles, 2000, 53, 2201.
6. T. Kinoshita, S. Tatara, F. C. Ho, and U. Sankawa, Phytochemistry, 1989, 28, 147.
7. (a) J. H. Sheu, Y. K. Cheng, H. F. Chung, P. J. Sung, and S. F. Lin, Heterocycles, 1996, 43, 1751;

HETEROCYCLES, Vol. 86, No. 1, 2012
513
(b) J. H. Sheu, Y. K. Chen, and Y. L. V. Hong, J. Org. Chem., 1993, 58, 5784; (c) J. H. Sheu, Y. K.
Chen, and Y. L. V. Hong, Tetrahedron Lett., 1991, 32, 1045; (d) J. H. Sheu, Y. K. Chen, H. F.
Chung, S. F. Lin, and P. J. Sung, J. Chem. Soc., Perkin Trans. 1, 1998, 1959; (e) K. F. Cheng, Y. C.
Kong, and T. Y. Chan, J. Chem. Soc., Chem. Commun., 1985, 48.
8. (a) M. Ishikura, H. Komatsu, K. Yamada, T. Abe, and R. Yanada, Heterocycles, 2007, 71, 2325; (b)
M. Ishikura, R. Uemura, K. Yamada, and R. Yanada, Heterocycles, 2006, 68, 2349.
9. There has been a report that indole-substituted methylbutenylindole was used for the dimerization: J.
H. Sheu, C. A. Chen, and B. H. Chen, Chem. Commun., 1999, 203.
10. Imine 5 (derived from 3-methylcrotonaldehyde and benzylamine) was distilled under reduced
pressure; see G. D. Joly and E. N. Jacobsen, J. Am. Chem. Soc., 2004, 126, 4102.
11. The reaction mechanism of the cleavage of the OMe group was supposed as follows:
TMSCl
7e
1
+
N
N
N
H
O
H
Bn
O=CH2
HCl
H
TMS N
H
Cl-
CO2Ph