Creation of new promoters for plant's root growth: its application for the syntheses of vulcanine and borreline, and for combating desertification at gobi desert in inner mongolia 1#

Article abstract of DOI:10.3987/COM-07-S(U)31

Abstract - Various new 2-substituted indole-3-carbaldehydes are prepared. Structurally related alkaloids, vulcanine and borreline, are synthesized as well. Among the compounds, 2-haloindole-3-carbaldehydes are found to be potent promoters of plant's root growth. Its successful preliminary application is reported for making Gobi desert in Inner Mongolia full of plant.

Full text of DOI:10.3987/COM-07-S(U)31

HETEROCYCLES, Vol. 73, 2007
537
HETEROCYCLES, Vol. 73, 2007, pp. 537 - 554. © The Japan Institute of Heterocyclic Chemistry
Received, 27th June, 2007, Accepted, 24th August, 2007, Published online, 28th August, 2007. COM-07-S(U)31
CREATION OF NEW PROMOTERS FOR PLANT’S ROOT GROWTH:
ITS APPLICATION FOR THE SYNTHESES OF VULCANINE AND
BORRELINE, AND FOR COMBATING DESERTIFICATION AT GOBI
DESERT IN INNER MONGOLIA1#
Masanori Somei,*2 Shinsuke Sayama, Katsumi Naka, Kotaro Shinmoto, and
Fumio Yamada
Division of Pharmaceutical Sciences, Graduate School of Natural Science and
Technology, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan
Corresponding author: e-mail address: syamoji_usa@r9.dion.ne.jp
Abstract – Various new 2-substituted indole-3-carbaldehydes are prepared.
Structurally related alkaloids, vulcanine and borreline, are synthesized as well.
Among the compounds, 2-haloindole-3-carbaldehydes are found to be potent
promoters of plant’s root growth. Its successful preliminary application is
reported for making Gobi desert in Inner Mongolia full of plant.
We have conceived an idea3 that the metabolites of tryptophan have each own function in vivo and are
promising targets for developing new drugs. In our project for discovering biologically active
compounds among the metabolites, we have focused on the derivatives4 of indole-3-carbaldehyde and
indole-3-carboxylic acid, involving the corresponding 1-hydroxy- and 1-alkoxyindole derivatives, on the
basis of our 1-hydroxyindole hypothesis.3 During the study for about 25 years, we have found various
types of plant growth regulators.5 Other groups have found daikon6 (Raphanus sativus, 1a, Scheme 1)
and wasabi (Eutrema japonicum) phytoalexins7 (1b) which are good examples for the biologically active
derivatives of indole-3-carbaldehyde and indole-3-carboxylic acid.
On the other hand, as for a starting material in a synthetic study, we make it a rule to utilize a bulk
chemical.8 Because when the target compound shows the expected biological activity, if it is needed
widely by the ultimate customers, it should be manufactured in the factory and supplied in a large
quantity. This is the reason why we have employed 2,3-dihydroindole (2) as a starting material
throughout our study.
#dedicated to Prof. Dr. Ivar Ugi.

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HETEROCYCLES, Vol. 73, 2007
With an aim to discover plant’s root promoter, we chose 2-haloindole-3-carbaldehydes (3a–j) and their
derivatives (4, 5, 7, 8, 11—13, 15–17) as target compounds. Part of this work was published as a
preliminary communication.1b In this paper, we describe their syntheses from 2 and the application for
the synthesis of closely related alkaloids, vulcanine9 (4) and borreline10 (5c). In addition, we have
succeeded in creating potent activators for plant’s root growth. With these compounds in hand, we are
now challenging to make Gobi desert in Inner Mongolia full of plant for preventing bai (yellow sand)
from generation and for stopping global warming.
Scheme 1
R1
Br
Br
N
X
N
N
O
N
N
O
H
R2
OMe
OR
OMe
9
10
6
1
2
d) R1 = CHO; R2 = H
a) R = H; X = H
b) R = Me; X = H
c) R = Ts; X = H
d) R = Me; X = I
a) R1 = CHO; R2 = OMe
b) R1 = CO2Me; R2 = OMe
c) R1 = CHO; R2 = OH
e) R1 = CHO;
R2 = OCH2CH2
N
NMe
CHO
R1
CHO
CHO
3
CHO
X
2
O2N
N
H
O
O2N
N
N
Br
N
R
N
R
1
H
H
15
16
17
7
8
3
11
a) R = OH
b) R = H
a) X = Br; R = H
b) X = Cl; R = H
c) X = Br; R = OMe
d) X = I; R = H
e) X = I; R = OMe
f) X = Br; R = OH
g) X = Br; R = Me
c) R = OMe
R2 SnR1
3
R2
R1
R1
H
15
a
14
a
4
NO2
OH
CHO
Br
n-Bu
n-Bu
OH
OH
h) X = Br; R = CH2CH CMe2
i) X = Br; R = CH2C CH
j) X = Br; R = CH2CH CH2
N
Br
N
b
c
b
c
CO2Me
H
CO2Me
H
12
N
N
d
e
f
Me
Me
Me
d
e
f
Me
Me
N
N
H
NO2
CH2OH
Br
N
N
N
N
R
N
Br
N
H
H
H
H
OH
5
4
13
a) R = H; b) R = CO2Me; c) R = Me
I. Creation of New Promoters for Plant’s Root Growth
According to our synthetic method3 for 1-hydroxyindole (6a) and its derivatives, 1-methoxyindole (6b)
and 1-tosyloxyindole (6c) were prepared from 2 in 70 and 23% yields, respectively.3 We then tried the
synthesis of 3a by the treatment of 6c with POBr3 based on the finding that 3b11 was produced by the

HETEROCYCLES, Vol. 73, 2007
539
reaction of 6c with POCl3 in 67% yield. In fact, however, 3a was not obtained under various examined
reaction conditions.
In order to obtain 3a, we next attempted to utilize 1-methoxy and 1-hydroxy derivatives, because we
found the treatment of 1-hydroxy-6-nitroindole-3-carbaldehyde12 (7a) with POBr3 gave an 82% yield of
2-bromo-6-nitroindole-3-carbaldehyde (8) together with 6-nitroindole-3-carbaldehyde (7b, 11%).
Therefore, 6b was converted to 1a in 90% yield as reported previously3 by Vilsmeier-Haack reaction.
The desired 1-hydroxyindole-3-carbaldehyde (1c) was obtained by treating 1a with KI in DMF-H2O (3:1,
v/v) at 160°C in 55% yield together with indole-3-carbaldehyde (1d) and unreacted 1a in 3 and 33%
yields, respectively. Quantitative production of 1c was realized by the reaction of 1a with DABCO (10
mol eq.) in DMF-H2O (3:1, v/v) at 100°C. Interestingly, when the same reaction was carried out in DMF
without a proton source, major product (61%) was 1-[2-(4-methylpiperazin-1-yl)ethoxy]indole-3-car-
baldehyde (1e), and 1c became a minor product (28%). The mechanism of the formation of 1e was
discussed in the previous paper.4a These new ether cleavage reactions were also applicable to
1-methoxy-6-nitroindole-3-carbaldehyde (7c). Thus, the former KI method gave 7a, 7b, and 7c in 58, 4,
and 22% yields, respectively, while the latter DABCO method4a provided 7a in 90% yield.
Although bromination of 1a with Br2 in AcOH at 100°C afforded poor yield of
2-bromo-1-methoxyindole-3-carbaldehyde (3c, 15%) with a mixture of inseparable 5- and
6-bromocompounds, reaction of 1c with POBr3 in THF proceeded as expected and 3a was obtained in
33% yield together with a 21% yield of 1d.
In order to improve the yield of 3a, alternative route13a was explored from 6b. Bromination of 6b with
NBS in t-BuOH resulted in the formation of 3,3-dibromo-1-methoxy-2-oxindole13a (9) in 50% yield.
Reductive debromination of 9 to 1-methoxy-2-oxindole13a—c (10) was carried out with Zn-AcOH at room
temperature in 91% yield. Then, 1-methoxy group was removed by catalytic hydrogenation with 10%
Pd/C and atmospheric hydrogen to afford 2-oxindole (11) in 95% yield, which is commercially available
but an expensive chemical. Subsequent Vilsmeier reaction of 11 with POBr3-DMF afforded 3a in 77%
yield.1b Application of the same reaction conditions to 10 provided (3c) in 84% yield.
2-Iodoindole-3-carbaldehyde (3d) was prepared in 62% yield by heating 3a with CuI and KI in DMF
though
its
separation
from
the
unreacted
3a
was
difficult.
Preparation
of
2-iodo-1-methoxyindole-3-carbaldehyde (3e) was carried out in 70% yield by the Vilsmeier reaction of
2-iodo-1-methoxyindole (6d), which was obtained according to our reported procedures from 2.14
Treatment of 3c with BBr3 in anhydrous CH2Cl2 at 0°C provided 2-bromo-1-hydroxyindole-3-
carbaldehyde (3f) in 14% yield in addition to 2,6-dibromoindole-3-carbaldehyde (12) and unreacted 3c in
16 and 32% yields, respectively. Interestingly, the same reaction at reflux condition resulted in the
predominant formation of 12 in 61% yield. The structure of 12 was determined by comparison of the

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HETEROCYCLES, Vol. 73, 2007
1H-NMR spectrum with that of 2,6-dibromoindol-3-ylmethanol (13), which was produced by the
reduction of 12 with NaBH4 in 67% yield. The proton signal at the 4-position of 13 appeared at δ 7.55 (d,
J=8.5 Hz), while the corresponding proton of 12 appeared at δ 8.19 (d, J=8.5 Hz). The observed
anisotropy effect of the formyl group on 12 clearly proved their structures as shown in Scheme 1.
1-Substituted 2-bromoindole-3-carbaldehydes were easily prepared as follows. Thus, the reactions of 3a
with MeI, 3-methyl-2-butenyl bromide, propargyl bromide, and allyl bromide in the presence of
n-Bu4NBr and K2CO3 as a base provided 1-methyl- (3g), 1-(3-methyl-2-butenyl)- (3h), 1-propargyl- (3i),
and 1-allyl-2-bromoindole-3-carbaldehydes (3j) in 98, 92, 91, and 98% yields, respectively.
II. Syntheses of Vulcanine and Borreline
In order to introduce a carbon side chain directly into the 2-position of 3a, improved Heck reaction15a,b
seemed to be promising among various palladium catalyzed cross coupling reactions.15a-d In fact, the
Heck reaction of 3a with 2-methyl-3-buten-2-ol gave the desired 2-(3-hydroxy-3-methyl-1-butenyl)-
3-indolecarboxaldehyde (15a) in 0~15% yield under various examined reaction conditions: changes in
concentrations of reactants and catalyst, reaction time, temperature.
On the other hand, modified Stille reaction15c was found to meet our end. Thus, 15a was obtained in 87%
yield upon treatment of 3a with tributyl(3-hydroxy-3-methyl-1-butenyl)tin (14a) in the presence of
n-Bu4NCl and a catalytic amount of Pd(OAc)2. Under similar reaction conditions, the reactions of 3a
with tin reagents, such as 14b—f, afforded the corresponding 15b—f in 67, 68, 38, 39, and 5% yields,
respectively.
We next converted 15a into (E,E)-2-methyl-4-[3-(2-nitrovinyl)indol-2-yl]-3-buten-2-ol (16) in 93% yield
by the nitroaldol reaction with CH3NO2 and NH4OAc as a catalyst. Subsequent reduction of 16 with
NaBH4 in MeOH afforded (E)-2-methyl-4-[3-(2-nitroethyl)indol-2-yl]-3-buten-2-ol (17) in 96% yield.
With the desired 17 in hand, we next employed our reductive aminocyclization reaction.16 Thus, the
reaction of 17 with zinc in refluxing methanolic hydrochloric acid resulted in the formation of
1-(2-methyl-1-propenyl)-1,2,3,4-tetrahydro-β-carboline (5a) in 50% yield. Subsequent treatment of 5a
with t-BuOCl in THF generated vulcanine9 (4) in 51% yield. On the other hand, the reaction of 5a with
ClCOOMe and Et3N gave an 85% yield of 2-methoxycarbonyl-1-(2-methyl-1-propenyl)-1,2,3,4-tetrahy-
dro-β-carboline (5b), which finally led to borrerine10 (5c) in 70% yield by the reduction with LiAlH4 in
anhydrous THF.
Spectral data of 4 and 5c are identical with those reported by Hesse and co-workers9 and by Sakai and
co-workers,10 respectively.
III. Biological Evaluation for the Plant’s Root Growth

HETEROCYCLES, Vol. 73, 2007
541
Typical results, obtained after culturing the germinated seeds of rice (Nihonbare) and cucumber
(Sagamihanpaku) at 25°C for 6 days, are shown in Table 1. In the case of aq. 3 ppm solution of 3a, the
average root length of the rice is 68% longer than that of the control (100%), while the average root
length of cucumber is 113%. On the other hand, the effect of a 50 ppm aq. solution of 16 on the rice
seeds was 168%. In the case of cucumber, a 3 ppm aq. solution of 16 promoted the root length up to
190%. Thus, almost all compounds described in this paper (3—5, 7, 8, 11—13, 15—17) showed various
degree of activity for plant’s root promotion and we named them SOMRE compounds. Among them,
SOMRE No. 1 (3a) and No. 4 (3d) have most potent activity. The detailed results will be reported
elsewhere in due course.
Table 1. Average Root Length of Rice and Cucumber
Plant and Root
Length of
Rice
Cucumber
Control: 46.8 mm (100%)
Control: 12.1 mm (100%)
the Control
Concentration of the Sample (ppm)
Concentration of the Sample (ppm)
Sample
50
12.5
3
0.8
50
12.5
3
0.8
CHO
Br
100 105 113
100 100 118
120 180 190
98
14
140 168
130
N
H
3a
CHO
101
146 136 120
168 133 113
100
N
H
OH
15a
16
NO2
114
109
N
H
OH
IV. Combating Desertification at Gobi Desert in Inner Mongolia
With new root growth encouragers (SOMRE compounds) in hand, we applied them to the wild plant
Calligonum alaschanicum (a kind of sand jujube) and Hedysarum scoparium Fisch et C.A. Mey at Gobi
desert in Inner Mongolia for combating desertification. After several trials in the desert, we have
disclosed that the 2-bromo compounds (3a, 3c: SOMRE No. 1, No. 3) have high germination rate and are

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HETEROCYCLES, Vol. 73, 2007
suitable for any tested wild plant. 2-Iodocompounds (3d, 3e: SOMRE No. 4, No. 5) have lower
germination rate, but they are found to be more effective than the 2-bromo compounds as for the root
growth.
On the other experiment at Gobi desert, seeds of Calligonum alaschanicum were divided into 5 groups
and each group was dipped for 30 min into a 1, 3, 10 ppm aq. solution of 3a, a 2 ppm aq. solution of
indole-3-acetic acid (IAA, the reference), and H2O (the control), respectively. Experiment farmland was
divided into 5 parts as well. Seeds of each group were separately sprinkled to the divided farmlands on
ditches of 5 cm depth and they were covered with sand. They were brought up for 73 days (from August
2 to October 14, 2005) under natural environment of the desert except for watering every one week. We
then dug grown young plants and compared the average root length. The results are summarized in Table
2. As is evident from Table 2, the solutions of 3a showed a remarkable effect on the plant’s root growth.
Especially, a 1 ppm aq. solution of 3a encouraged the plant’s root about 2 times longer and 8—15 times
heavier than those of the reference and the control.
Table 2. Plant Growth for 73 Days at Gobi Desert in Inner Mongolia
Planting FAugust 2, 2005. Digging FOctober 14, 2005
IAA
Sample
3a
10 ppm
3a
3 ppm
3a
1 ppm
D
(2 ppm,
Control
D1/2
Root
Reference)
Root
Length
(L cm)
18.0
1.5
21.0
1.2
22.5 36.0 42.5
1/2 L
Width
(D mm)
1.5
0.8
2.0
2.0
6.0
4.0
L
D1/2
(mm)
1.0
1.0
1/2 L
Weight
(mg)
310
620
360 1,390 4,980
It is well known the plants grown from the seeds usually freeze to death during the severe cold winter at
Gobi desert. In between May, 2006 and April, 2007, we have confirmed that the plants from the seeds
treated with SOMRE No. 1 have not frozen to death, because they have three times longer root (53.2 cm)
than the control (19.1 cm) and can survive through a year. In April, 2007, we dipped young plant’s roots
of 2,700 sand jujubes into the 1 ppm aq. solution of SOMRE No. 1 for 30 min and planted them at Gobi

HETEROCYCLES, Vol. 73, 2007
543
desert of about 2 hectares. Under natural environment without artificial watering we observed their
growth. Two months later, their survival rate is 87.9%, much better than 78.3% of the control group.
With these successful results in hand, we are now continuing preliminary field experiment to make Gobi
desert green. Our compounds (SOMRE No. 1, No. 4, related compounds) make the wild plant’s roots
longer enough to reach to the ground water. They would change Gobi desert again to the area with full of
plants as it was 300 years ago. They would be useful for preventing disastrous global warming and for
production of more food as a new technology. We believe SOMRE compounds become “the medicine
for the earth.”
EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. IR
spectra were determined with Shimadzu IR-420 and Horiba FT-720 spectrophotometers, UV spectra
1
with a Shimadzu UV 2400 PC spectrophotometer, and H-NMR spectra with JEOL FX-100, JEOL EX
270, and JEOL GSX 500 spectrometers, with tetramethylsilane as an internal standard. MS were
recorded on Hitachi M-80 and JEOL JMS-SX 102A spectrometer. Preparative thin-layer
chromatography (p-TLC) was performed on Merck Kiesel-gel GF245 (Type 60) (SiO2). Column
chromatography was performed on silica gel (SiO2, 100—200 mesh, from Kanto Chemical Co., Inc.)
throughout the present study.
1-Hydroxyindole-3-carbaldehyde (1c) and 1-[2-(4-methylpiperazin-1-yl)ethoxy]indole-3-carbalde-
hyde (1e) from 1-Methoxyindole-3-carbaldehyde (1a) — i) Method A: DABCO (1.05 g, 9.36 mmol)
was added to a solution of 1a3,17 (159.8 mg, 0.91 mmol) in DMF (5 mL) and the mixture was heated at
100°C for 21 h with stirring. After addition of H2O, the solution was made acidic (pH 4) with 6% HCl,
and the whole was extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4,
and evaporated under reduced pressure to leave a brown solid, which was column-chromatographed on
SiO2 with CHCl3–MeOH (97:3, v/v) to give 1c (41.4 mg, 28%). The aqueous layer was made basic (pH
10) with 8% NaOH and the whole was extracted with AcOEt. The organic layer was washed with brine,
dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was
column-chromatographed on SiO2 with CHCl3–MeOH (95:5, v/v) to give 1e (159.8 mg, 61%). 1c and 1e
were identical with the samples prepared according to our previous paper.4a 1e·2HCl: mp 220—230°C
(decomp., pink powder, recrystallized from MeOH). IR (KBr): 1660cm–1. 1H-NMR (DMSO-d6: D2O=5:1,
v/v) δ: 2.90 (3H, s), 3.41 (2H, t, J=4.9 Hz), 3.48 (8H, br s), 4.68 (2H, t, J=4.9 Hz), 7.37 (1H, dd, J=7.8,
7.1 Hz), 7.45 (1H, dd, J=7.8, 7.1 Hz), 7.71 (1H, d, J=7.8 Hz), 8.17 (1H, d, J=7.8 Hz), 8.66 (1H, s), 9.89
(1H, s). Anal. Calcd for C16H21N3O2·2HCl: C, 53.34; H, 6.43; N, 11.66. Found: C, 53.08; H, 6.41; N,
11.53.

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HETEROCYCLES, Vol. 73, 2007
ii) Method B: DABCO (386.3 mg, 3.45 mmol) was added to a solution of 1a (61.2 mg, 0.35 mmol) in
DMF–H2O (3:1, v/v, 2 mL) and the mixture was heated at 100°C for 21 h with stirring. After addition of
H2O, the whole was made acidic (pH 4) with 6% HCl and extracted with AcOEt. The organic layer was
washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a brown solid,
which was column-chromatographed on SiO2 with CHCl3–MeOH (97:3, v/v) to give 1c (55.0 mg, 98%).
iii) Method C: KI (2.753 g, 16.6 mmol) was added to a solution of 1a (32.3 mg, 0.19 mmol) in
DMF–H2O (3:1, v/v, 4 mL) and the mixture was heated at 160°C for 24 h with stirring. After the same
work-up as described in the method B, unreacted 1a (10.5 mg, 33%), 1d (0.7 mg, 3%), and 1c (16.3 mg,
55%) were obtained in the order of elution.
2-Bromoindole-3-carbaldehyde (3a) from 1-Hydroxyindole-3-carbaldehyde (1c) — A solution of 1c
(27.6 mg, 0.17 mmol) in anhydrous THF (3 mL) was added to POBr3 (310.0 mg, 1.08 mmol) and the
mixture was stirred at rt for 15 h. After addition of H2O, the whole was extracted with CHCl3–MeOH
(95:5, v/v). The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced
pressure to leave an oil, which was column-chromatographed on SiO2 with AcOEt–hexane (1:1, v/v) to
give 3a (12.6 mg, 33%) and 1d (5.3 mg, 21%) in the order of elution. 3a: mp 209—210.5°C1b
(decomp., colorless needles, recrystallized from MeOH, lit.18 mp 196—198°C). IR (KBr): 3100, 1645
1
cm–1. H-NMR (DMSO-d6) δ: 6.96—7.54 (3H, m), 8.14—8.88 (1H, m), 9.82 (1H, s). MS m/z: 223 and
225 (M+, 79Br and 81Br).
2-Bromoindole-3-carbaldehyde (3a) from 2-Oxindole (11) — A solution of POBr3 (8 mL, 0.08 mol)
in anhydrous CHCl3 (20 mL) was added to anhydrous DMF (30 mL, 0.39 mol), and the mixture was
stirred at rt for 25 min. To the resulting viscous solution was added a solution of 11 (4.06 g, 0.03 mol) in
anhydrous CHCl3 (60 mL), and then the mixture was stirred at rt for 13 h. During the above procedures,
when magnetic stirring became difficult because of the increase in viscosity, supersonic wave generator
was employed as an assistant. After cooling to 0°C, the whole was made basic by adding 40% aqueous
NaOH and extracted with CH2Cl2–MeOH (9:1, v/v). The organic layer was washed with brine, dried
over Na2SO4, and evaporated under reduced pressure to leave a crystalline solid, which was
recrystallized from MeOH to give 3a (5.281 g, 77%).
2-Chloroindole-3-carbaldehyde (3b) from 1-Tosyloxyindole (6c) — A solution of Vilsmeier reagent
(460.9 mg, 1.68 mmol), prepared from POCl3 (767.6 mg, 5.01 mmol) and DMF (581.6 mg, 7.96 mmol),
in DMF (0.5 mL) was added to a solution of 6c (48.1 mg, 0.17 mmol) in DMF (1 mL) at 0°C and the
mixture was stirred at rt for 5.5 h. The whole was made basic with 8% aqueous NaOH and extracted with
AcOEt. The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced
pressure to leave a solid, which was column-chromatographed on SiO2 with CH2Cl2 to give 3b (20.1 mg,
67%). Physical data were identical with those of the authentic sample.11

HETEROCYCLES, Vol. 73, 2007
545
2-Bromo-1-methoxyindole-3-carbaldehyde (3c) from 1-Methoxy-2-oxindole (10)4) — Anhydrous
DMF (9 mL) was added to a solution of POBr3 (0.2 mL) in anhydrous CHCl3 (6 mL) at 0°C and stirring
was continued at rt for 15 min. To the resulting solution was added a solution of 1013 (236.3 mg, 1.45
mmol) in DMF (5 mL) at 0°C and the mixture was stirred at rt for 12 h. The whole was made basic with
8% aqueous NaOH and extracted with AcOEt. The organic layer was washed with brine, dried over
Na2SO4, and evaporated under reduced pressure to leave a solid, which was column-chromatographed on
SiO2 with AcOEt–hexane (1:3, v/v) to give 3c (307.5 mg, 84%). 3c: mp 97—98°C (colorless needles,
recrystallized from MeOH). IR (KBr): 1653 cm-1. 1H NMR (CDCl3) δ: 4.19 (3H, s), 7.31 (1H, ddd, J=7.6,
7.3, 1.2 Hz), 7.36 (1H, ddd, J=7.8, 7.3, 1.2 Hz), 7.45 (1H, dd, J=7.8, 1.2 Hz), 8.32 (1H, dd, J=7.6, 1.2
79
81
Hz), 9.98 (1H, s). MS m/z: 253 and 255 (M+, Br and Br). Anal. Calcd for C10H8BrNO: C, 47.27; H,
3.17; N, 5.51. Found: C, 47.02; H, 3.22; N, 5.33.
2-Iodoindole-3-carbaldehyde (3d) from 3a — KI (1.144 g, 6.89 mmol) and CuI (659.5 mg, 3.46 mmol)
were added to a solution of 3a (152.8 mg, 0.68 mmol) in DMF (15 mL) and the mixture was heated at
120°C for 48 h. After evaporation of the solvent under reduced pressure, H2O was added to the residue.
The whole was extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, and
evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with
AcOEt–hexane (1:1, v/v) to give an inseparable mixture (151.9 mg) of 3a and 3d in a ratio of 1:3.1
(1H-NMR analysis). The yields of 3a and 3d were calculated to be 29.8 mg (20%) and 122.1 mg (62%),
respectively. To obtain 2 mg of pure 3d, repeated HPLC and column-chromatography were required. 3d:
1
mp 224—226°C (colorless needles, recrystallized from MeOH). IR (KBr): 3138, 1639 cm–1. H-NMR
(DMSO-d6) δ: 7.19 (1H, td, J=7.5, 1.2 Hz), 7.22 (1H, td, J=7.5, 1.2 Hz), 7.42 (1H, dd, J=7.5, 1.2 Hz),
8.09 (1H, dd, J=7.5, 1.2 Hz), 9.72 (1H, s), 12.81 (1H, br s). High-resolution MS m/z: Calcd for
C9H6INO: 270.9494. Found: 270.9478.
2-Iodo-1-methoxyindole-3-carbaldehyde (3e) from 2-Iodo-1-methoxyindole (6d) — POCl3 (0.2 mL,
2.15 mmol) was added to DMF (2 mL, 25.8 mmol) at 0°C and the stirring was continued at rt for 15 min.
To the solution was added a solution of 6d14 (137.1 mg, 0.50 mmol) in DMF (2 mL) at 0°C and the
mixture was stirred at rt for 2 h. The whole was made basic with 8% aqueous NaOH and extracted with
AcOEt. The organic layer was washed with brine, dried over Na2SO4, and evaporated under the reduced
pressure to leave a solid, which was column-chromatographed on SiO2 with AcOEt–hexane (1:5, v/v) to
give 3e (105.6 mg, 70%). 3e: mp 132—134°C (colorless needles, recrystallized from MeOH). IR (KBr):
1645 cm–1. 1H-NMR (CDCl3) δ: 4.18 (3H, s), 7.29 (1H, t, J=7.3 Hz), 7.33 (1H, t, J=7.3 Hz), 7.46 (1H, d,
J=7.3 Hz), 8.33 (1H, d, J=7.3 Hz), 9.79 (1H, s). MS m/z: 301 (M+). Anal. Calcd for C10H8INO2: C,
39.89; H, 2.68; N, 4.65. Found: C, 40.33; H, 2.87; 4.47.
2,6-Dibromoindole-3-carbaldehyde (12) with/without 2-Bromo-1-hydroxyindole-3-carbaldehyde

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(3f) from 2-Bromo-1-methoxyindole-3-carbaldehyde (3c) — i) Method A: BBr3 (2 mL, 21.2 mmol)
was added to a solution of 3c (50.0 mg, 0.20 mmol) in anhydrous CH2Cl2 (5 mL) at 0°C and the mixture
was refluxed for 21 h with stirring. The mixture was poured into an ice water and the whole was
extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, and evaporated
under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with CHCl3–MeOH
(95:5, v/v) to give 12 (36.3 mg, 61%). 12: mp 269—270°C (decomp., colorless prisms, recrystallized
from MeOH). IR (KBr): 3082, 1631 cm-1. 1H NMR (CD3OD) δ: 7.35 (1H, dd, J=8.5, 1.8 Hz), 7.56 (1H,
1
d, J=1.8 Hz), 8.04 (1H, d, J=8.5 Hz), 9.91 (1H, s). H NMR (CDCl3) δ: 7.41 (1H, dd, J=8.5, 1.2 Hz),
7.51 (1H, d, J=1.2 Hz), 8.17 (1H, d, J=8.5 Hz), 8.76 (1H, br s), 10.01 (1H, s). MS m/z: 301, 303, and 305
(M+ 79Br2, 79Br81Br, and 81Br2). Anal. Calcd for C9H5Br2NO: C, 35.68; H, 1.66; N, 4.62. Found: C, 35.64;
H, 1.72; N, 4.57.
ii) Method B: BBr3 (4.0 mL, 42.3 mmol) was added to a solution of 3c (97.0 mg, 0.33 mmol) in
anhydrous CH2Cl2 (10 mL) at 0°C and the mixture was stirred at rt for 24 h. After the same work-up as
described in the Method A, the crude product was column-chromatographed on SiO2 with CHCl3 to give
unreacted 3c (30.8 mg, 32%), 12 (18.2 mg, 16%), and 3f (12.7 mg, 14%) in the order of elution. 3f: mp
192—194°C (decomp., colorless needles, recrystallized from AcOEt–hexane). IR (KBr): 1630 cm–1.
1H-NMR (CD3OD) δ: 7.27 (1H, dd, J=7.8, 7.3 Hz), 7.34 (1H, J=7.8, 7.3 Hz), 7.50 (1H, d, J=7.8 Hz),
79
8.16 (1H, d, J=7.8 Hz), 9.86 (1H, s). High-resolution MS m/z: Calcd for C9H6 BrNO2: 238.9582. Found:
81
238.9579. Calcd for C9H6 BrNO2: 240.9561. Found: 240.9556.
2-Bromo-1-methylindole-3-carbaldehyde (3g) from 3a — A solution of MeI (969.2 mg, 6.83 mmol) in
THF (10 mL) was added to a mixture of 3a (1.07 g, 4.75 mmol), Bu4NBr (306.9 mg, 0.952 mmol), and
K2CO3 (3.55 g, 25.7 mmol) in THF (60 mL), and the mixture was stirred at rt for 5 h. After addition of
brine, the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was washed with brine,
dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was
column-chromatographed on SiO2 with CH2Cl2 to give 3g (1.11 g, 98%). 3g: mp 118—118.5°C
1
(colorless prisms, recrystallized from hexane). IR (KBr): 1638 cm–1. H-NMR (CDCl3) δ: 3.84 (3H, s),
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81
7.14—7.36 (3H, m), 8.14—8.36 (1H, m), 9.98 (1H, s). MS m/z: 237 and 239 (M+, Br and Br). Anal.
Calcd for C10H8BrNO: C, 50.45; H, 3.39; N, 5.88. Found: C, 50.44; H, 3.35; N, 6.09.
2-Bromo-1-(3-methyl-2-buten-1-yl)indole-3-carbaldehyde (3h) from 3a — A solution of prenyl
bromide (1.06 g, 7.17 mmol) in THF (10 mL) was added to a mixture of 3a (1.02 g, 4.54 mmol), Bu4NBr
(300.8 mg, 0.933 mmol), and K2CO3 (3.57 g, 25.8 mmol) in THF (60 mL), and the mixture was stirred at
rt for 6 h. After the same work-up as described in the preparation of 3g, 1.22 g (92%) of 3h was obtained.
3h: 78.5—79°C (colorless needles, recrystallized from hexane). IR (KBr): 1650 cm–1. 1H-NMR (CDCl3)
δ: 1.75 (3H, d, J=1.2 Hz), 1.92 (3H, d, J=1.2 Hz), 4.83 (2H, d, J=7.0 Hz), 5.18 (1H, th, J=7.0, 1.2 Hz),

HETEROCYCLES, Vol. 73, 2007
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7.11—7.35 (3H, m), 8.15—8.39 (1H, m). 10.00 (1H, s). MS m/z: 291 and 293 (M+, 79Br and 81Br). Anal.
Calcd for C14H14BrNO: C, 57.55; H, 4.83; N, 4.79. Found: C, 57.58; H, 4.84; N, 4.80.
2-Bromo-1-propargylindole-3-carbaldehyde (3i) from 3a — A solution of propargyl bromide (826.6
mg, 6.95 mmol) in THF (10 mL) was added to a mixture of 3a (1.00 g, 4.50 mmol), Bu4NBr (280.1 mg,
0.88 mmol), and K2CO3 (3.19 g, 23.1 mmol) in THF (40 mL), and the mixture was stirred at rt for 22 h.
After addition of brine, the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was
washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a crystalline solid,
which was recrystallized from MeOH to give 3i (1.01 g) as colorless flakes. The mother liquor was
subjected to p-TLC on SiO2 with CH2Cl2–hexane (3:2, v/v) as a developing solvent. Extraction of the
band having an Rf value of 0.35—0.43 with CH2Cl2–MeOH (95:5, v/v) gave 3i (60.9 mg). Total yield of
1
3i was 1.07 g (91%). 3i: mp 151.5—152.5°C. IR (KBr): 1636 cm–1. H-NMR (CDCl3) δ: 2.37 (1H, t,
J=2.5 Hz), 5.00 (2H, d, J=2.5 Hz), 7.14—7.54 (3H, m), 8.14—8.39 (1H, m), 10.00 (1H, s). MS m/z: 261
and 263 (M+, 79Br and 81Br). Anal. Calcd for C12H8BrNO: C, 54.98; H, 3.08; N, 5.34. Found: C, 54.82; H,
2.98; N, 5.47.
1-Allyl-2-bromolindole-3-carbaldehyde (3j) from 3a — A solution of allyl bromide (108.0 mg, 0.89
mmol) in THF (2 mL) was added to a mixture of 3a (100.3 mg, 0.45 mmol), Bu4NBr (29.3 mg, 0.09
mmol), and K2CO3 (307.8 mg, 2.23 mmol) in THF (6 mL), and the mixture was stirred at rt for 1 h. After
the same work-up as described in the preparation of 3g, 115.3 mg (98%) of 3j was obtained. 3j: mp
87—88°C (colorless prisms, recrystallized from CHCl3). IR (KBr): 1652 cm–1. 1H-NMR (CDCl3) δ: 4.90
(2H, ddd, J=5.0, 1.8, 1.2 Hz), 5.23 (1H, dt, J=17.0, 1.8 Hz), 5.26 (1H, dt, J=10.5, 1.2 Hz), 5.94 (1H, ddt,
J=17.0, 10.5, 5.0 Hz), 7.26—7.33 (3H, m), 8.31—8.34 (1H, m), 10.06 (1H, s). MS m/z: 263 and 265 (M+,
81
79Br and Br). Anal. Calcd for C12H10BrNO·1/4H2O: C, 53.65; H, 3.94; N, 5.21. Found: C, 53.84; H,
3.73; N, 5.21.
1- Hydroxy-6-nitroindole-3-carbaldehyde (7a) from 1-Methoxy-6-nitroindole-3-carbaldehyde (7c)
— i) Method A: The formation of 7a in 90% yield by the reaction of 7c with DABCO was reported in
the preceding paper.12
ii) Method B: A solution of KI (960.0 mg, 5.78 mmol) in H2O (1 mL) was added to a solution of 7c
(32.8 mg, 0.15 mmol) in DMF (3 mL), and the mixture was heated at 120°C for 36 h with stirring. After
evaporation of the solvent under reduced pressure, AcOEt was added to the residue. The same work-up
of the organic layer as described in the Method A gave unreacted 7c (7.3 mg, 22%), 7b (1.1 mg, 4%),
and 7a (17.9 mg, 58%) in the order of elution. 7a is identical with the authentic sample.12
2-Bromo-6-nitroindole-3-carbaldehyde (8) from 7a — POBr3 (529.4 mg, 1.85 mmol) was added to a
solution of 7a (60.9 mg, 0.30 mmol) in anhydrous THF (4 mL) and the mixture was stirred at rt for 5 h.
After evaporation of the solvent, H2O was added to the residue, and the whole was extracted with

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CHCl3–MeOH (95:5, v/v). The organic layer was washed with brine, dried over Na2SO4, and evaporated
under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with
AcOEt–hexane (1:1, v/v) to give 8 (65.3 mg, 82%) and 7b (6.2 mg, 11%) in the order of elution. 8: mp
1
296—298°C (decomp., colorless prisms, recrystallized from AcOEt). IR (KBr): 1631 cm–1. H-NMR
(DMSO-d6) δ: 8.12 (1H, dd, J=8.8, 1.6 Hz), 8.24 (1H, d, J=8.8 Hz), 8.27 (1H, d, J=1.6 Hz), 9.95 (1H, s).
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81
The proton at the 1-position did not appear. MS m/z: 268 and 270 (M+, Br and Br). Anal. Calcd for
C9H5BrN2O3: C, 40.18; H, 1.87; N, 10.41. Found: C, 40.16; H, 1.93; N, 10.47.
3,3-Dibromo-1-methoxy-2-oxindole (9) from 1-methoxyindole (6b) — NBS (3.637 g, 20.43 mmol)
was added to a solution of 6b (1.001g, 6.81 mmol) in t-BuOH (70 mL) and the mixture was stirred at rt
for 30 min. After evaporation of the solvent, H2O was added to the residue. The whole was extracted
with benzene. The organic layer was washed with brine, dried over Na2SO4, and evaporated under
reduced pressure to leave a yellow solid, which was column-chromatographed on SiO2 with
CH2Cl2–hexane (2:1, v/v) to give 9 (1.281 g, 59%). 9: mp 73—75°C (pale yellow prisms, recrystallized
1
from CH2Cl2–hexane). IR (KBr): 1745 cm–1. H-NMR (CDCl3) δ: 4.06 (3H, s), 6.95 (1H, dd, J=7.7,
1.5 Hz), 7.15 (1H, br dt, J=1.5, 7.7 Hz), 7.34 (1H, br dt, J=1.5, 7.7 Hz), 7.56 (1H, dd, J=7.8, 1.5 Hz). MS
79
81
m/z: 319, 321, and 323 (M+, Br and Br). Anal. Calcd for C9H7Br2NO2: C, 33.64; H, 2.18; N, 4.36.
Found: C, 33.51; H, 2.09; N, 4.51.
1- Methoxy-2-oxindole (10) from 9 — Zink powder (103.2 mg, 1.6 mmol) was added to a solution of 9
(50.5 mg, 0.16 mmol) in AcOH (5 mL) and the mixture was stirred at rt for 1.5 h. Unreacted Zn was
filtered off and washed with CH2Cl2–MeOH (95:5, v/v). H2O was added to the combined washing and
the filtrate. The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced
pressure to leave an oil, which was column-chromatographed on SiO2 with CH2Cl2 to give 10 (16.6 mg,
65%). Spectral data are identical with the authentic sample prepared according to our previous
procedures.13a,b
2-Oxindole (11) from 10 — A solution of 10 (155.3 mg, 0.95 mmol) in MeOH (10 mL) was
hydrogenated in the presence of 10% Pd/C (50 mg) at rt and 1 atm for 1 h. Catalyst was filtered off and
the filtrate was evaporated under reduced pressure to leave a crystalline solid, which was
column-chromatographed on SiO2 with CH2Cl2 to give 11 (120.4 mg, 95%), whose physical data were
identical with the commercially available sample.
2,6-Dibromoindol-3-ylmethanol (13) from 12 — NaBH4 (150.0 mg, 3.95 mmol) was added to a
solution of 12 (65.2 mg, 0.22 mmol) in MeOH (10 mL), and the mixture was stirred at rt for 1 h. After
evaporation of the solvent under reduced pressure, AcOEt was added to the residue. The whole was
washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was
column-chromatographed on SiO2 with CHCl3–MeOH (95:5, v/v) to give 13 (44.2 mg, 67%). 13:

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1
colorless oil. IR (film): 3398, 3213, 1614 cm–1. H-NMR (CDCl3) δ: 1.48 (1H, br s), 4.80 (2H, s), 7.26
(1H, dd, J=8.5, 1.7 Hz), 7.43 (1H, d, J=1.7 Hz), 7.55 (1H, d, J=8.5 Hz), 8.18 (1H, br s). High-resolution
79
79
MS m/z: Calcd for C9H7 Br2NO: 302.8895. Found: 302.8915. Calcd for C9H7 Br81BrNO: 304.8874.
81
Found: 304.8852. Calcd for C9H7 Br2NO: 306.8854. Found: 306.8829.
E-2-(3-Hydroxy-3-methyl-1-butenyl)indole-3-carbaldehyde (15a) from 3a — General Procedure: A
solution of 3a (405.4 mg, 1.81 mmol), (3-hydroxy-3-methyl-1-butenyl)tributyltin (14a, 1.00 g, 2.81
mmol), Pd(OAc)2 (42.3 mg, 0.19 mmol), and Bu4NCl (1.00 g, 3.61 mmol) in DMF (6 mL) was heated at
115—120°C for 3 h with stirring. After evaporation of the solvent under reduced pressure, brine was
added, and the whole was extracted with AcOEt–MeOH (95:5, v/v). The organic layer was washed with
brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was
column-chromatographed on SiO2 with AcOEt–hexane (2:1, v/v) to give 15a (362.1 mg, 87%). 15a: mp
1
194—195°C (colorless prisms, recrystallized from MeOH). IR (KBr): 3165, 2975, 1614 cm–1. H-NMR
(CD3OD) δ: 1.47 (6H, s), 6.75 (1H, d, J=16.0 Hz), 7.02—7.48 (3H, m), 7.20 (1H, d, J=16.0 Hz),
7.99—8.23 (1H, m), 10.18 (1H, s). MS m/z: 229 (M+). Anal. Calcd for C14H15NO2: C, 73.34; H, 6.59; N,
6.11. Found: C, 73.17; H, 6.60; N, 6.32.
Methyl (E)-3-(3-Formylindol-2-yl)acrylate (15b) from 3a — In the general procedure for 15a, 3a
(102.2 mg, 0.46 mmol), 2-(methoxycarbonyl)vinyltributyltin (14b, 254.2 mg, 0.68 mmol), Pd(OAc)2
(12.1 mg, 0.05 mmol), and Bu4NCl (248.6 mg, 0.90 mmol) were used. After the same work-up as
described in the preparation of 15a, 70.2 mg (67%) of 15b was obtained. 15b: mp 261—262°C. IR
1
(KBr): 3050, 1703, 1628 cm–1. H-NMR (pyridine-d5) δ: 3.72 (3H, s), 6.95 (1H, d, J=16.0 Hz),
7.25—7.49 (3H, m), 8.50 (1H, d, J=16.0 Hz), 8.59—8.77 (1H, m), 10.71 (1H, s). The NH proton signal
was not observed. MS m/z: 229 (M+). Anal. Calcd for C13H11NO3: C, 68.11; H, 4.84; N, 6.11. Found: C,
67.89; H, 4.76; N, 6.04.
2-Phenylindole-3-carbaldehyde (15c) from 3a — In the general procedure for 15a, 3a (41.1 mg, 0.18
mmol), tetraphenyltin (14c, 117.3 mg, 0.27 mmol), Pd(OAc)2 (4.3 mg, 0.02 mmol), and Bu4NCl (97.7
mg, 0.35 mmol) were used. After the same work-up and column-chromatgraphy as described in the
preparation of 15a, 15c (27.7 mg, 68%) and 3a (3.9 mg, 10%) were obtained in the order of elution. 15c:
1
mp 260.5—263°C (colorless prisms, recrystallized from MeOH). IR (KBr): 3120, 1628 cm–1. H-NMR
(pyridine-d5) δ: 7.18—7.90 (8H, m), 8.53—8.91 (1H, m), 10.25 (1H, s). MS m/z: 221 (M+). Anal. Calcd
for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C, 81.51; H, 4.92; N, 6.35.
2-(3-Pyridyl)indole-3-carbaldehyde (15d) from 3a — In the general procedure for 15a, 3a (103.1 mg,
0.46 mmol), (3-pyridyl)trimethyltin (14d, 221.0 mg, 0.91 mmol), Pd(OAc)2 (9.7 mg, 0.04 mmol), and
Bu4NCl (261.3 mg, 0.94 mmol) were used. After the same work-up and column-chromatgraphy as
described in the preparation of 15a, 15d (39.1 mg, 38%), 15e (10.9 mg, 15%), and 1d (5.5 mg, 8%) were

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obtained in the order of elution. 15d: mp 246—246.5°C (colorless needles, recrystallized from MeOH).
1
IR (KBr): 3430, 3130, 1628 cm–1. H-NMR (pyridine-d5) δ: 7.28—7.70 (4H, m), 8.14 (1H, ddd, J=8.0,
2.2, 1.8 Hz), 8.75—8.96 (2H, m), 9.27 (1H, dd, J=2.2, 0.8 Hz), 10.41 (1H, s). MS m/z: 222 (M+). Anal.
Calcd for C14H10N2O: C, 75.65; H, 4.54; N, 12.61. Found: C, 75.48; H, 4.77; N, 12.50.
2-Methylindole-3-carbaldehyde (15e) from 3a — In the general procedure for 15a, 3a (467.8 mg, 2.09
mmol), tetramethyltin (14e, 562.2 mg, 3.12 mmol), Pd(OAc)2 (42.7 mg, 0.19 mmol), and Bu4NCl (1.34 g,
4.84 mmol) were used. After the same work-up and column-chromatgraphy as described in the
preparation of 15a, 15e (130.0 mg, 39%) and 1d (18.1 mg, 6%) were obtained in the order of elution.
15e: mp 204—205°C (colorless needles, recrystallized from MeOH). IR (KBr): 3250, 1635 cm–1.
1H-NMR (CD3OD) δ: 2.63 (3H, s), 6.89—7.39 (3H, m), 7.79—8.12 (1H, m), 9.82 (1H, s). MS m/z: 159
(M+). Anal. Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.50; H, 5.62; N, 8.82.
2-(2-Pyridyl)indole-3-carbaldehyde (15f) from 3a — In the general procedure for 15a, 3a (100.5 mg,
0.45 mmol), 14f (1.07 g, 4.43 mmol), Pd(OAc)2 (10.9 mg, 0.05 mmol), and Bu4NCl (246.1 mg, 0.89
mmol) were used. After the same work-up and column-chromatgraphy as described in the preparation of
15a, unreacted 3a (21.4 mg, 21%), 15f (5.0 mg, 5%), 15e (0.5 mg, 1%), and 1d (2.4 mg, 4%) were
obtained in the order of elution. 15f: mp 225.5—226.5°C (colorless needles, recrystallized from MeOH).
IR (KBr): 3060, 1619 cm–1. 1H-NMR (pyridine-d5) δ: 7.12—7.70 (4H, m), 7.75 (1H, dd, J=7.5, 2.0 Hz),
8.70 (1H, dt, J=8.0, 1.0 Hz), 8.65—8.78 (1H, m), 8.78—8.98 (1H, m), 11.04 (1H, s). MS m/z: 222 (M+).
Anal. Calcd for C14H10N2O: C, 75.65; H, 4.54; N, 12.61. Found: C, 75.42; H, 4.38; N, 12.83.
(E,E)-2-Methyl-4-[3-(2-nitrovinyl)indol-2-yl]-3-buten-2-ol (16) from 15a — NH4OAc (736.1 mg,
9.50 mmol) was added to a solution of 15a (435.7 mg, 1.90 mmol) in MeNO2 (26 mL) and the mixture
was heated at 90°C for 4 h with stirring. After cooling to rt, the resulting precipitates (16, 406.1 mg)
were collected by filtration and washed with MeOH. The filtrate and washings were combined and H2O
was added. The whole was extracted with CH2Cl2–MeOH (95:5, v/v). The organic layer was washed
with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a crystalline solid, which
was column-chromatographed on SiO2 with CH2Cl2–MeOH (95:5, v/v) to give 16 (75.7 mg). Total yield
of 16 was 481.8mg (93%). 16: mp 246.5—247°C (decomp., red needles, recrystallized from MeOH). IR
1
(KBr): 3250, 1578, 1360 cm–1. H NMR (pyridine-d5) δ: 1.55 (6H, s), 7.02 (1H, d, J=16.0 Hz),
7.26—7.59 (4H, m), 7.85—8.05 (1H, m), 8.52 (1H, d, J=13.2 Hz), 8.77 (1H, d, J=13.2 Hz). MS m/z: 272
(M+). Anal. Calcd for C15H16N2O3: C, 66.16; H, 5.92; N, 10.29. Found: C, 65.97; H, 5.89; N, 10.46.
(E)-2-Methyl-4-[3-(2-nitroethyl)indol-2-yl]-3-buten-2-ol (17) from 16 — NaBH4 (173.5 mg, 4.59
mmol) was added to a solution of 16 (206.0 mg, 0.76 mmol) in MeOH (30 mL) and the mixture was
stirred at rt for 1 h. After addition of AcOEt, the whole was washed with brine, dried over Na2SO4, and
evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with

HETEROCYCLES, Vol. 73, 2007
551
AcOEt–hexane (1:1, v/v) to give 17 (199.5 mg, 96%). 17: mp 122.5—123°C (colorless prisms,
recrystallized from benzene). IR (KBr): 3520, 3310, 1554, 1380 cm–1. 1H-NMR (CD3OD) δ: 1.23 (6H, s),
3.48 (2H, t, J=7.5 Hz), 4.62 (2H, t, J=7.5 Hz), 6.31 (1H, d, J=16.0 Hz), 6.71 (1H, d, J=16.0 Hz),
6.83—7.52 (4H, m). MS m/z: 274 (M+). Anal. Calcd for C15H18N2O3: C, 65.67; H, 6.61; N, 10.21. Found:
C, 65.89; H, 6.58; N, 10.23.
1-(2-Methyl-1-propenyl)-1,2,3,4-tetrahydro-β-carboline (5a) from 17 — A solution of 17 (174.9 mg,
0.64 mmol) in THF (19.5 mL) was added to a mixture of Zn powder (897.2 mg, 13.7 mmol) [washed
with 6% HCl (4 mL)] in 6% HCl (6.5 mL) at 0°C and the mixture was refluxed for 5 min with stirring.
Unreacted Zn was filtered off and the filtrate was evaporated under reduced pressure. The residue was
made basic by adding 8% aqueous NaOH and the whole was extracted with CH2Cl2–MeOH (95:5, v/v).
The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to
leave an oil, which was column-chromatographed on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:2:0.2,
v/v) to give 5a (22.5 mg, 50%). 5a: mp 160—161°C (colorless prisms, recrystallized from CH2Cl2, lit.,10
mp 158—159°C). IR (KBr): 3400, 1092 cm–1. 1H-NMR (CDCl3) δ: 1.82 (3H, d, J=1.2 Hz), 1.88 (3H, d,
J=1.2 Hz), 2.65—2.89 (2H, m), 2.89—3.55 (2H, m), 4.83 (1H, br d, J=9.5 Hz), 5.26 (1H, dt, J=9.5, 1.2
Hz), 6.92—7.33 (3H, m), 7.33—7.53 (1H, m), 7.64 (1H, br s). MS m/z: 226 (M+). Anal. Calcd for
C15H18N2·1/4H2O: C, 78.05; H, 8.07; N, 12.13. Found: C, 78.47; H, 8.09; N, 11.84.
2-Methoxycarbonyl-1-(2-methyl-1-propenyl)-1,2,3,4-tetrahydro-β-carboline (5b) from 5a — A
solution of ClCO2Me (38.6 mg, 0.41 mmol) in CH2Cl2 (1 mL) was added to a solution of 5a (54.0 mg,
0.24 mmol) and Et3N (80.0 mg, 0.79 mmol) in CH2Cl2 (3 mL) and the mixture was stirred at rt for 2 h.
Saturated NaHCO3 was added and the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The organic
layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil,
which was recrystallized from MeOH to give 5b (47.5 mg) as colorless prisms. The mother liquor was
subjected to p-TLC on SiO2 with CH2Cl2–MeOH (95:5, v/v) as a developing solvent. Extraction from the
band having an Rf value of 0.93—1.00 with CH2Cl2–MeOH (95:5, v/v) gave 5b (10.3 mg). Total yield of
5b was 58.7 mg (85%). 5b: mp 186—189°C (lit.,10 mp 180—181°C). IR (KBr): 3400, 3040, 1092 cm–1.
1H NMR (CDCl3) δ: 1.77 (3H, d, J=1.4 Hz), 1.98 (3H, d, J=1.4 Hz), 2.64—2.88 (2H, m), 2.88—3.37
(1H, m), 3.73 (3H, s), 4.39 (1H, d, J=12.5 Hz), 5.30 (1H, d, J=10.0 Hz), 5.88 (1H, d, J=10.0 Hz),
6.91—7.32 (3H, m), 7.36—7.52 (1H, m), 7.59 (1H, br s). High-resolution MS m/z: Calcd for
C17H20N2O2: 284.1524. Found: 284.1526.
Borrerine (5c) from 5b — LiAlH4 (98.6 mg, 2.60 mmol) was added to a solution of 5b (46.3 mg, 0.16
mmol) in THF (8 mL) at 0°C and the mixture was refluxed for 5 h with stirring. After addition of MeOH
and 10% aqueous Rochelle salt under ice cooling, the whole was extracted with CH2Cl2–MeOH (95:5,
v/v). The organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced

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pressure to leave an oil, which was subjected to p-TLC on SiO2 with CHCl3–MeOH–28% aq. NH3
(46:5:0.5, v/v) as a developing solvent. Extraction from the band having an Rf value of 0.74—0.90 with
CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) gave 5c (28.2 mg, 70%). 5c: mp 105—106°C (colorless
1
prisms, recrystallized from hexane, lit.,10 mp 102—103°C). IR (KBr): 3200 cm–1. H-NMR (CDCl3) δ:
1.86 (3H, d, J=1.2 Hz), 1.88 (3H, d, J=1.2 Hz), 2.48—3.29 (4H, m), 4.05 (1H, dt, J=9.5, 1.2 Hz), 5.18
(1H, br d, J=9.5 Hz), 6.92—7.34 (3H, m), 7.34—7.63 (2H, m). High-resolution MS m/z: Calcd for
C16H20N2: 240.1625. Found: 240.1630.
Vulcanine (4) from 5a — A solution of t-BuOCl (42.4 mg, 0.39 mmol) in THF (1 mL) was added to a
suspension of 5a (37.0 mg, 0.16 mmol) and powdered NaOH (32.1 mg, 0.80 mmol) in THF (4 mL) and
the mixture was stirred at rt for 64 h. H2O was added and the whole was extracted with AcOEt. The
organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave
an oil, which was subjected to p-TLC on SiO2 with AcOEt–hexane (1:1, v/v) as a developing solvent.
Extraction from the band having an Rf value of 0.47—0.65 with AcOEt gave 4 (18.5 mg, 51%). 4: pale
yellow oil. IR (CHCl3): 1645, 1623, 1567, 1492, 1452, 1420, 1380, 1316, 1235 cm–1. 1H-NMR (CDCl3)
δ: 2.00 (3H, d, J=1.2 Hz), 2.01 (3H, d, J=1.2 Hz), 6.60 (1H, t, J=1.2 Hz), 7.28 (1H, ddd, J=8.1, 6.4, 1.7
Hz), 7.51 (1H, ddd, J=8.1, 1.7, 1.0 Hz), 7.53 (1H, ddd, J=8.1, 6.4, 1.0 Hz), 7.82 (1H, d, J=5.4 Hz), 8.11
13
(1H, d, J=8.1 Hz), 8.46 (1H, d, J=5.4 Hz), 8.57 (1H, br s, disappeared on addition of D2O). C-NMR
(CDCl3) δ: 20.5, 26.7, 111.9, 113.0, 119.0, 120.3, 121.6, 121.8, 128.8, 129.5, 134.0, 136.8, 140.7, 140.8,
143.8. UV λmax (MeOH) nm (log ε): 214 (4.36), 239 (4.49), 260 (sh, 4.23), 292 (4.14), 356 (3.79). MS
m/z: 222 (M+), 207, 182, 103. High-resolution MS m/z: Calcd for C15H14N2: 222.1157. Found: 222.1154.
4·HCl: mp 189—192°C (yellow needles, recrystallized from Et2O–MeOH, lit.,9 mp 103°C). IR (KBr):
3340, 1640, 1599, 1442, 761 cm–1. 1H-NMR (CD3OD) δ: 1.93 (3H, d, J=1.2 Hz), 2.22 (3H, d, J=1.2 Hz),
6.74 (1H, t, J=1.2 Hz), 7.47 (1H, ddd, J=8.1, 6.8, 1.0 Hz), 7.76 (1H, dt, J=8.3, 1.0 Hz), 7.80 (1H, ddd,
J=8.3, 6.8, 1.0 Hz), 8.35 (1H, d, J=6.4 Hz), 8.41 (1H, dt, J=8.1, 1.0 Hz), 8.55 (1H, d, J=6.4 Hz).
13C-NMR (CD3OD) δ: 20.9, 26.6, 113.9, 114.2, 116.6, 121.5, 123.0, 124.1, 129.5, 133.1, 134.8, 135.2,
137.4, 145.4, 152.5. Anal. Calcd for C15H14N2·HCl·1/4H2O: C, 68.44; H, 5.93; N, 10.64. Found: C,
68.51; H, 5.83; N, 10.68.
ACKNOWLEDGMENTS
The authors express their cordial gratitude to Dr. Y. Kamuro (Nissan Chemical Ind. Ltd.) for the
biological test (rice and cucumber). They are deeply indebted to Mr. T. Minamide, a member of “The
NPO Juridical Person for Making the World Desert Green” for observing the root growth for 73 days in
the hottest season at Gobi desert in Inner Mongolia.

HETEROCYCLES, Vol. 73, 2007
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REFERENCES AND NOTES
1. a) This report is part 131 of a series entitled “The Chemistry of Indoles”. b) Part of this work was
reported as a preliminary communication: M. Somei, S. Sayama, K. Naka, and F. Yamada,
Heterocycles, 1988, 27, 1585. c) Part 130: M. Somei, F. Yamada, Y. Makita, and M. Somei, ibid.,
2007, 72, 599.
2. Professor Emeritus of Kanazawa University. Present address: 2-40-3 Sodani, Hakusan-shi, Ishikawa,
Japan 920-2101.
3. M. Somei, Topics in Heterocyclic Chemistry, Vol. 6, ed. by S. Eguchi, Springer-Verlag, Berlin, 2006,
pp. 77—111; M. Somei, Advances in Heterocyclic Chemistry, Vol. 82, ed. by A. R. Katritzky,
Elsevier Science, USA, 2002, pp. 101—155; M. Somei, Heterocycles, 1999, 50, 1157; M. Somei, J.
Synth. Org. Chem., 1991, 49, 205; M. Somei and T. Kawasaki, Heterocycles, 1989, 29, 1251.
4. a) K. Yamada, S. Tomioka, N. Tanizawa, and M. Somei, Heterocycles, 2004, 63, 1601 and
references cited therein. b) K. Yamada, Y. Kanbayashi, S. Tomioka, and M. Somei, ibid., 2002, 57,
1627 and references cited therein. c) The first report of the project: M. Somei, T. Hasegawa, and C.
Kaneko, ibid., 1983, 20, 1983.
5. M. Somei, K. Kizu, M. Kunimoto, and F. Yamada, Chem. Pharm. Bull., 1985, 33, 3696; M. Somei, F.
Yamada, M. Kunimoto, and C. Kaneko, Heterocycles, 1984, 22, 797. See also reference 3.
6. M. Takasugi, K. Monde, N. Katsui, and A. Shirota, Symposium Papers, The 29th Symposium on The
Chemistry of Natural Products, Sapporo, Aug. 1987, p. 629; M. Somei, H. Ohnishi, and Y. Shoken,
Chem. Pharm. Bull., 1986, 34, 677; M. Somei and T. Shoda, Heterocycles, 1981, 16, 1523.
7. F. Yamada, K. Yamada, H. Takeda, and M. Somei, Heterocycles, 2001, 55, 2361; M. Somei, A.
Tanimoto, H. Orita, F. Yamada, and T. Ohta, ibid., 2001, 54, 425; M. S. C. Pedras and J. L.
Sorensen, Phytochemistry, 1998, 49, 1959; these authors did not cite us in spite of using our original
1-methoxyindole synthetic method.3 See also reference 4b.
8. M. Somei, Chemistry, 2007, 62, 16.
9. T. Gozler, B. Gozler, A. Linden, and M. Hesse, Phytochemistry, 1996, 43, 1425.
10. E. Yamanaka, N. Shibata, and S. Sakai, Heterocycles, 1984, 22, 271; M. Doe de Maindreville, J.
Levy, F. Tillequin, and M. Koch, J. Nat. Prod., 1983, 46, 310; J. L. Pousset, J. Kerharo, G. Maynart,
X. Monseur, A. Cave, and R. Goutarel, Phytochemistry, 1973, 12, 2308.
11. K. E. Schulte, J. Reisch, and U. Stoess, Arch. Pharmaz., 1972, 305, 523.
12. K. Yamada, S. Tomioka, N. Tanizawa, and M. Somei, Heterocycles, 2004, 63, 1601.
13. a) T. Kawasaki, A. Kodama, T. Nishida, K. Shimizu, and M. Somei, Heterocycles, 1991, 32, 221. b)
M. Somei, F. Yamada, T. Kurauchi, Y. Nagahama, M. Hasegawa, K. Yamada, S. Teranishi, H. Sato,
and C. Kaneko, Chem. Pharm. Bull., 2001, 49, 87. c) W. B. Wright Jr. and K. H. Collins, J. Am.

554
HETEROCYCLES, Vol. 73, 2007
Chem. Soc., 1956, 78, 221.
14. M. Somei and A. Kodama, Heterocycles, 1992, 34, 1285.
15. a) R. F. Heck, Palladium Reagents in Organic Synthesis, Academic Press Inc. (London) Ltd., 1985.
b) M. Somei, T. Hasegawa, T. Suzuki, and M. Wakida, Abstracts of Papers, The 105th Annual
Meeting of Pharmaceutical Society of Japan, Kanazawa, April 1985, p. 679; T. Jeffery, J. Chem.
Soc., Chem. Commun., 1984, 1287. c) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508. d) M.
Somei, F. Yamada, and K. Naka, Chem. Pharm. Bull., 1987, 35, 1322; M. Somei, H. Amari, and Y.
Makita, ibid., 1986, 34, 3971; M. Somei, T. Hasegawa, and C. Kaneko, Heterocycles, 1983, 20,
1983.
16. F. Yamada, T. Hasegawa, M. Wakita, M. Sugiyama, and M. Somei, Heterocycles, 1986, 24, 1223.
17. R. M. Acheson, “New Trends in Heterocyclic Chemistry,” ed. by R. B. Mitra, N. R. Ayyangar, V. N.
Gogte, R. M. Acheson, and N. Cromwell, Elsevier Scientific Pub. Co. New York, 1979, pp. 1—33;
R. M. Acheson, P. G. Hunt, D. M. Littlewood, B. A. Murrer, and H. E. Rosenberg, J. Chem. Soc.,
Perkin Trans. 1, 1978, 1117.
18. T. L. Gilchrist and P. D. Kemmitt, Tetrahedron, 1997, 53, 4447; H. von Dobeneck, D. Wolkenstein,
and G. Blankenstein, Chem. Ber., 1969, 102, 1347.