A one-pot access to cycloalkano[1,2-a]indoles through an intramolecular alkyl migration reaction in indolylborates

Article abstract of DOI:10.1016/j.tet.2005.10.045

A novel one-pot protocol for the preparation of cycloalkano[1,2-a]indoles by way of an intramolecular alkyl migration reaction in cyclic indolylborates is described. NaOMe was found to act as a successful trialkylboryl-protecting group against to the lithiation at the C2 of the indole ring. Treatment of cyclic indolylborates with electrophiles produced cycloalkano-[1,2-a]indoles.

Full text of DOI:10.1016/j.tet.2005.10.045

Tetrahedron 62 (2006) 1015–1024
A one-pot access to cycloalkano[1,2-a]indoles through an
intramolecular alkyl migration reaction in indolylborates
a
b
Minoru Ishikura,a, Wataru Ida and Kazuo Yanada
*
aFaculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
bFaculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagatoge-Cho, Hirakata, Osaka 573-0101, Japan
Received 5 September 2005; accepted 11 October 2005
Available online 7 November 2005
Abstract—A novel one-pot protocol for the preparation of cycloalkano[1,2-a]indoles by way of an intramolecular alkyl migration reaction
in cyclic indolylborates is described. NaOMe was found to act as a successful trialkylboryl-protecting group against to the lithiation at the C2
of the indole ring. Treatment of cyclic indolylborates with electrophiles produced cycloalkano-[1,2-a]indoles.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
development of a novel one-pot access to [a]-annelated
indoles by the use of the 1,2-alkyl migration process in
indolylborate (6).7
The rich chemistry of organoboron compounds has
provided fertile ground for the development of pivotal
synthetic methodologies.1 While an inter- or intra-
molecular alkyl migration from boron to carbon in
organoboron compounds has been well recognized as a
valuable synthetic tool for regioselective and stereospecific
bond formation,2 its use for intramolecular cyclization
has been scarcely known.3 In our continuing program
to develop trialkyl(1H-indol-2-yl)borate as a versatile
synthetic intermediate for the construction of indole
derivatives,4 an intramolecular alkyl migration from
boron to the C2 of the indole ring in indolylborates
has also been proven to be successful, leading to
2,3-disubstituted indoles in a one-pot treatment. Hence,
we have become interested in the unprecedented use of the
alkyl migration process in indolylborates, and previously
reported a novel one-pot protocol for the preparation of
carbazole derivatives based on the intramolecular 1,2-alkyl
migration reaction in indolylborates, in which p-allyl
palladium complexes were adopted as successful intra-
molecular electrophiles.5
2. Results and discussion
As shown in Scheme 1, we initially envisioned that alkyl
migration triggered by intermolecular attack of electrophile
(H2O) on the C-3 of the indole ring in cyclic indolylborate
(6) might provide the cyclization product (8) after oxidation
of 7, in which implementation of the synthetic plan first
required an adequate protocol for the in situ generation of 6.
Our initial expectation to form 6 via 2-lithioindole (A)
involved straightforward lithiation of the starting indole (1),
followed by treatment with dialkylboranes, but all
attempted experiments have met with failure. Alternatively,
we anticipated that if 2-lithioindole (5) is available by the
lithiation at the C-2 of the indole ring of alkylborane (2), the
following spontaneous cyclization might possibly provide
cyclic indolylborate (6).
Initially, we attempted the lithiation with tert-BuLi at the
C-2 of the indole ring in alkylboranes (2), readily generated
by treatment of indole (1a) with 9-borabicyclo[3.3.1]nonane
(9-BBN) in THF at room temperature. However, an
oxidative work-up of the reaction mixture allowed only
the isolation of alcohol (10a) in 40% yield, which possibly
involved the formation of tetraalkylborate (B) from the
predominant interaction between the trialkylboryl group of
2 and tert-BuLi. With this in mind, we needed a feasible
trialkylboryl-protecting group that would persist until the
lithiation at the C2 of 2 was complete, and after that, would
As the core structure of [a]-annelated indole is present in a
number of biologically active indole derivatives such as
mitomycin and vincamine, the development of methods for
the construction of [a]-annelated indole nuclei has been the
subject of a number of reports.6 We have set about the
Keywords: Cyclic indolylborate; Hydroboration; Intramolecular alkyl
migration; [a]-Annelated indoles.
*
Corresponding author. Tel./fax: C81 133 23 1245;
e-mail: ishikura@hoku-iryo-u.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.045

1016
M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
5
H-BR2
6
X
Li
N
( )n
X
7
N
( )n
A
1
a: n=1 X=H
b: n=1 X=7-Me
c: n=1 X=5-OMe
d: n=1 X=5-NO2
e: n=2 X=H
H-BR2 (9-BBN)
THF
f: n=3 X=H
Li+
[O]
tert-BuLi
tert-Bu
X
N
( )n
N
N
(n=1, X=H)
2
B
BR2
BR2
-
OH
10a
40%
(BR2=9-borabicyclo[3.3.1]nonyl)
NaOMe
Na+
NaOMe
Li
Na+
tert-BuLi
X
X
N
OMe
X
N
( )n
Li
OMe
N
( )n
( )n
5
3
BR2
BR2
-
4
BR2
-
H+
Li+
H2O
-
BR2
-
X
BR2
N
( )n
X
X
BR2
N
( )n
N
6
( )n
7
[O]
X
7
+
X
N
( )n
N
5
OH
8
10
( )n
a: n=1 X=H
a: n=1 X=H
b: n=1 X=NO2
c: n=2 X=H
d: n=3 X=H
b: n=1 X=5-Me
c: n=1 X=7-OMe
d: n=2 X=H
e: n=3 X=H
Scheme 1.
be removed to restore the trialkylboryl group. We were
pleased to find that the presence of NaOMe provided
marked protection against the lithiation of 2 by the
formation of methoxyborate (3), and the following work-
up of the reaction mixture with H2O2 in NaOH solution
afforded 8, accompanied by a small amount of 10. The
reaction outcome can be interpreted as follows: (1)
hydroboration of 1 with 9-BBN produces alkylborane (2).
(2) Treatment of 2 with NaOMe forms methoxyborate (3).
(3) Subsequent lithiation of 3 with tert-BuLi generates
2-lithioindole (4), which is accompanied by spontaneous
formation of indolylborate (6) via elimination of the
methoxide anion (4 to 5). (4) Intramolecular 1,2-alkyl
migration in 6 provides [a]-annelated indole (8) after
oxidation of 7. Alcohols (10) were possibly produced by
way of oxidation of 5 or B.
As summarized in Table 1, the use of NaOMe (1.1 equiv),
tert-BuLi (2.2 equiv) and TMEDA (2.2 equiv) in THF was
adequate to effect the one-pot transformation of 1a to 8a,
and the conditions were applied to further investigations.
Hydroboration of 5d brought about 6 (nZ1, XZ5-NO2)
in situ, which was subsequently subjected to the reaction.
However, the desired cyclization product was not obtained
in this transformation and only alcohol (10b) was isolated
from the complex reaction mixtures.

M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
1017
Table 1. One-pot preparation of 8 from 1a
1
NaOMe (equiv)
tert-BuLi (equiv)
TMEDA (equiv)
Yield (%) of 8
Yield (%) of 10
nZ1 XZH
nZ1 XZH
nZ1 XZH
nZ1 XZH
nZ1 XZH
nZ1 XZH
nZ1 XZH
nZ1 XZ7-Me
nZ1 XZ5-OMe
nZ1 XZ5-NO2
nZ1 XZH
nZ1 XZH
—
2.2
2.2
2.2
1.1
3.0
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
—
1.1
2.2
2.2
2.2
2.2
2.2
8a (16)
8a (62)
8a (22)
8a (14)
8a (47)
8a (40)
8a (50)
8b (53)
8c (60)
—
10a (20)
—
1.1
2.2
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
10a (10)
10a (22)
10a (7)
10a (10)
10a (5)
—
—
10b (40)
10c (5)
10d (8)
8d (60)
8e (42)
a Yield (%) of 8 and 10 based on 1.
Treatment of 6 (XZH) with various electrophiles such as
alkyl halides and p-allyl palladium complexes similarly
produced [a]-annelated indoles (9), which allowed the
introduction of various functional groups at the C3 of the
indole ring (Table 2). On the reaction of indolylborate
(6; nZ2, XZH) with 3-bromocyclohexene, borinate (9k)
was isolated as stable crystals in 35% yield after oxidation
of the reaction mixture, which was in contrast to the
formation of 9j and 9l from the reaction of 6 (nZ1,3,
XZH). Longer oxidation time and use of increased amount
of H2O2 did not effect the production of 9k. As there
are examples of the successful use of diphenyliodonium
ion as an electrophile toward the enolate anion,8 the
diphenyliodonium ion was also expected to be suitable for
the promotion of the alkyl migration in 6. The reaction of 6
(XZH, nZ1) with diphenyliodonium chloride in THF
under the same conditions afforded furanylindole (9t) in
30% yield as the only isolable product. This is probably
due to the alkyl migration in 6 (nZ1, XZH) caused by the
electrophilic attack of the furanium ion (C) arising from
the rapid oxidation of THF by diphenyliodonium ion9
(Scheme 2).
The alkyl migration reaction in indolylborates (12), derived
from indoles (11) having a substituent at the olefinic carbon,
was next examined. Indole (11a) was successfully
Table 2. One-pot preparation of 9 from 1 (XZH)a
E–X
E
n
Yield (%) of 9
Yield (%) of 10
CH3–I
–CH3
1
2
3
9a (55)
9b (40)
9c (30)
10a (10)
10c (12)
10d (22)
1
2
3
9d (59)
9e (40)
9f (30)
10a (10)
10c (10)
10d (15)
I–CH2CN
–CH2CN
1
2
3
9g (30)
9h (30)
9i (20)
10a (10)
10c (15)
10d (20)
Br–CH2CH]CH2
–CH2CH]CH2
1
2
3
9j (42)
—
9l (20)
10a (10)
—
10d (20)
b
1
2
3
9m (55)
9n (50)
9o (39)
10a (10)
10c (10)
10d (10)
1
2
3
9a (60)
9b (55)
9c (26)
10a (10)
10c (10)
10d (15)
–CH2CH]CH2
1
2
3
9p (58)
9q (50)
9i (40)
10a (10)
10c (15)
10d (20)
1
9s (42)
10a (10)
a Yield (%) of 9 and 10 based on 1.
b Compound 9k was isolated.

1018
M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
Br
[O]
B
6
B
O
N
(X=H, n=2)
THF
N
35%
9k
+
Li+
O
O
+
C
[O]
-
Ph-I-Ph Cl-
6
THF
BR2
N
N
(X=H, n=1)
30%
9t
(BR2=9-borabicyclo[3.3.1]nonyl)
Scheme 2.
transformed to 13a via 12 (RZMe). Otherwise, hydro-
boration of 11b became much more sluggish, requiring
forced reaction conditions (reflux for 2 h), and the following
steps were less effective in giving 13b in low yield,
accompanied by a substantial amount of alcohol (14b).
When indole (11c) bearing an alkoxy group was subjected
to the alkyl migration reaction, 1-allyl-2-oxyindole (17) was
isolated without the expected cyclization product. The rapid
elimination of the alkoxy group from borate (15) pre-
dominantly took place to generate 16, and the subsequent
oxidation gave rise to 17, as shown in Scheme 3.
Aqueous treatment of 19, derived from indoles (18) bearing a
substituent at the C-3 of the indole ring, affordrd [a]-annelated
indoles (9a, 20) and alcohols (10e, 21), respectively
(Scheme 4). In the case of 18b, LDA was employed for the
Li+
-
1) 9-BBN
2) NaOMe
N
BR2
N
3) tert-BuLi
11
12
R'
R'
a: R'=Me
b: R'=Ph
(BR2=9-borabicyclo[3.3.1]nonyl)
c: R'=OCH2OMe
1) H2O
2) [O]
+
N
N
13
14
OH
R'
R'
a: R=Me 65%
b: R=Ph 11%
a: R=Me 5%
b: R=Ph 30%
Li+
-
11c
1) 9-BBN
BR2
N
2) NaOMe
3) tert-BuLi
TMEDA
15
MeO
O
[O]
BR2
O
N
N
17
16
25%
Scheme 3.

M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
1019
R'
1) 9-BBN
2) NaOMe
R'
Li+
-
N
BR2
3) tert-BuLi
or LDA
N
18
19
a: R'=Me
b: R'=CO2Me
a: R'=Me
b: R'=CO2Me
(BR2=9-borabicyclo[3.3.1]nonyl)
R'
R'
1) H2O
2) [O]
+
N
N
OH
10e: R'=Me
21 : R'=CO2Me 10%
13%
9a: R'=Me
20: R'=CO2Me 16%
40%
δ 2.64
δ 2.29
NOE
H
H
Me
N
δ 0.03
Br
H
19a
B
δ 0.71
H
35%
22
Scheme 4.
lithiation at the C-2 of the indole ring in order to generate
indolylborate (19b). Otherwise, simply treating 19a with allyl
bromide and the following work-up of the reaction mixture
without a conventional oxidation allowed the isolation of
alkylborane (22) in 35% yield as stable crystals. The reaction
proceeded through the electrophilic attack of allyl bromide at
the C-3 of the indole ring in 19a with simultaneous alkyl
migration in an anti manner5 to produce 22, whose structure
was confirmed based on NOE experiments.
under an argon atmosphere, and the mixture was stirred
for 1.5 h. Sodium methoxide (2.2 mmol) was added to
the mixture, and after stirring for 30 min, TMEDA
(4.4 mmol) and tert-BuLi (1.5 M solution in pentane,
4.4 mmol) were added to the mixture at K20 8C. After
stirring for 2 h, the mixture was gradually raised to room
temperature, and stirred for 4 h. To the reaction mixture,
20% NaOH (10 mL) and 30% H2O2 (2 mL) were added
under ice-cooling and the whole was stirred for 30 min. The
mixture was diluted with ethyl acetate (100 mL), washed
with brine, and dried over MgSO4. The solvent was
removed, and the residue was separated by MPLC to
give 8 (with hexane/AcOEtZ100:1) and 10 (with hexane/
AcOEtZ1:1).
In summary, we have demonstrated a new one-pot access to
cycloalkano[1,2-a]indoles (9) by way of the unprecedented
use of an intramolecular alkyl migration process in
indolylborate (6). Further extension of the protocol for the
preparation of indole alkaloid is under way.
3.2.1. 2,3-Dihydro-1H-pyrrolo[1,2-a]indole (8a). Mp
1
77–78 8C (lit.10 78–79 8C). H NMR (CDCl3) d: 2.59 (tt,
2H, JZ6.8, 7.3 Hz), 3.00 (t, 2H, JZ7.3 Hz), 4.04 (t, 2H,
JZ6.8 Hz), 6.15 (s, 1H), 7.03 (dt, 1H, JZ1.4, 7.1 Hz), 7.10
(dt, 1H, JZ1.4, 7.1 Hz), 7.22 (d, 1H, JZ7.1 Hz), 7.53 (d,
1H, JZ7.1 Hz). 13C NMR (CDCl3) d: 24.1, 27.7, 43.4, 92.1,
109.3, 119.9, 120.1, 132.5, 133.2, 144.5. MS m/z: 157 (MC).
3. Experimental
3.1. General
Melting points were recorded on a Yamato MP21 and are
uncorrected. MS and high-resolution MS spectra were
recorded on a Micromass AutoSpec 3100 mass spectro-
meter. IR spectra were measured on a Hitachi Model 270-30
spectrometer. The NMR experiments were performed with a
JEOL JNM-LA300 or JNM-ECA500 spectrometer, and
chemical shifts are expressed in ppm (d) with TMS as an
internal reference. Medium pressure liquid chromatography
(MPLC) was performed on silica gel (Silica Gel 60N, Kanto
Chemical Co., Ltd).
3.2.2. 5-Methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole
(8b). Mp 90–91 8C (hexane). H NMR (CDCl3) d: 2.64 (s,
1
3H), 2.55–2.65 (m, 2H), 2.94 (t, 2H, JZ7.4 Hz), 4.36 (t, 2H,
JZ6.8 Hz), 6.11 (s, 1H), 6.81 (d, 1H, JZ7.9 Hz), 6.91 (t,
1H, JZ7.9 Hz), 7.34 (d, 1H, JZ7.9 Hz). 13C NMR (CDCl3)
d: 17.9, 23.7, 27.9, 46.5, 92.6, 118.1, 119.3, 120.2, 121.7,
132.3, 133.4, 144.7. MS m/z: 171 (MC). Anal. Calcd for
C12H13N: C, 84.17; H, 7.65; N, 8.18. Found: C, 84.38; H,
7.55; N, 8.24.
3.2. General procedure for the preparation of 8
3.2.3. 7-Methoxy-2,3-dihydro-1H-pyrrolo[1,2-a]indole
1
To a solution of 1 (2 mmol) in THF (10 mL), 9-BBN (0.5 M
solution in THF, 2.2 mmol) was added at room temperature
(8c). Mp 85–87 8C (lit.11 84–85 8C). H NMR (CDCl3) d:
2.50–2.60 (m, 2H), 2.97 (t, 2H, JZ7.8 Hz), 3.83 (s, 3H),

1020
M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
3.98 (t, 2H, JZ7.0 Hz), 6.08 (s, 1H), 6.77 (d, 1H, JZ
7.8 Hz), 7.02 (br s, 1H), 7.09 (d, 1H, JZ7.8 Hz). 13C NMR
(CDCl3) d: 24.4, 27.7, 43.7, 55.9, 92.0, 102.6, 109.9, 128.1,
133.6, 145.3, 153.9. MS m/z: 187 (MC).
d: 1.67–1.78 (m, 4H), 1.81–1.88 (m, 2H), 2.25 (s, 3H), 2.86
(t, 2H, JZ5.8 Hz), 4.13 (t, 2H, JZ5.2 Hz), 7.04 (t, 1H,
JZ7.8 Hz), 7.13 (t, 1H, JZ7.8 Hz), 7.23 (d, 1H, JZ
8.0 Hz), 7.48 (d, 1H, JZ8.0 Hz). 13C NMR (CDCl3) d: 8.8,
25.5, 28.0, 29.8, 31.3, 44.6, 105.5, 108.2, 118.3, 120.4,
128.3, 135.8, 139.1. MS m/z: 199 (MC). Anal. Calcd for
C14H17N: C, 84.37; H, 8.60; N, 7.03. Found: C, 84.42; H,
8.77; N, 7.01.
3.2.4. 6,7,8,9-Tetrahydropyrido[1,2-a]indole (8d). Mp
1
58–59 8C (lit.12 57–58 8C). H NMR (CDCl3) d: 1.80–1.95
(m, 2H), 2.00–2.15 (m, 2H), 2.97 (t, 2H, JZ6.3 Hz), 3.00 (t,
2H, JZ7.3 Hz), 4.04 (t, 2H, JZ6.4 Hz), 6.14 (s, 1H), 7.06
(dt, 1H, JZ1.5, 7.8 Hz), 7.13 (dt, 1H, JZ1.5, 7.8 Hz), 7.26
(d, 1H, JZ7.8 Hz), 7.52 (d, 1H, JZ7.8 Hz). 13C NMR
(CDCl3) d: 21.1, 23.3, 24.1, 42.1, 97.3, 108.4, 119.4, 119.9,
128.1, 136.1, 137.0. MS m/z: 171 (MC).
3.3.4. 9-Allyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole (9d).
1
IR (neat): 1660, 1640, 1610 cmK1. H NMR (CDCl3) d:
2.55 (tt, 2H, JZ7.2, 7.3 Hz), 2.92 (t, 2H, JZ7.3 Hz), 3.45
(d, 2H, JZ5.6 Hz), 3.99 (t, 2H, JZ7.2 Hz), 5.00 (dd, 1H,
JZ1.5, 10.0 Hz), 5.10 (dd, 1H, JZ1.7, 17.0 Hz), 6.02 (ddt,
1H, JZ17.0, 10.0, 5.6 Hz), 7.03 (dd, 1H, JZ7.8, 7.9 Hz),
7.09 (dd, 1H, JZ7.8, 7.9 Hz), 7.18 (d, 1H, JZ7.8 Hz), 7.49
(d, 1H, JZ7.9 Hz). 13C NMR (CDCl3) d: 23.1, 27.6, 29.3,
43.3, 102.9, 109.1, 114.3, 118.4, 118.5, 119.9, 132.3, 132.4,
137.4, 141.5. HR-MS m/z: Calcd for C14H15N: 197.1203.
Found: 197.1220.
3.2.5. 7,8,9,10-Tetrahydro-6H-azepino[1,2-a]indole (8e).
Mp 86–85 8C (lit.12 83–85 8C). 1H NMR (CDCl3) d: 2.59 (tt,
2H, JZ6.8, 7.3 Hz), 3.00 (t, 2H, JZ7.3 Hz), 4.04 (t, 2H,
JZ6.8 Hz), 6.15 (s, 1H), 7.03 (dt, 1H, JZ1.4, 7.1 Hz), 7.10
(dt, 1H, JZ1.4, 7.1 Hz), 7.22 (d, 1H, JZ7.1 Hz), 7.53 (d,
1H, JZ7.1 Hz). 13C NMR (CDCl3) d: 8.1, 28.6, 29.4, 31.0,
44.5, 98.9, 108.5, 118.8, 119.7, 120.2, 127.7, 136.8, 143.2.
MS m/z: 185 (MC).
3.3.5. 10-Allyl-6,7,8,9-tetrahydropyrido[1,2-a]indole
(9e). H NMR (CDCl3) d: 1.88–1.94 (m, 2H), 2.05–2.11
1
3.3. General procedure for the preparation of 9
(m, 2H), 2.89 (t, 2H, JZ6.3 Hz), 3.47 (d, 2H, JZ6.3 Hz),
4.04 (t, 2H, JZ6.3 Hz), 5.01 (dd, 1H, JZ1.0, 10.1 Hz), 5.09
(dd, 1H, JZ1.0, 17.1 Hz), 5.99 (tdd, 1H, JZ6.3, 10.1,
17.1 Hz), 7.09 (t, 1H, JZ7.8 Hz), 7.15 (t, 1H, JZ7.8 Hz),
7.26 (d, 1H, JZ7.8 Hz), 7.54 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 21.2, 22.5, 23.5, 28.5, 42.4, 107.0, 108.5, 114.2,
118.0, 119.1, 120.2, 127.9, 133.5, 136.0, 137.5. HR-MS m/z:
Calcd for C15H17N: 211.1361. Found: 211.1353.
To a solution of 1 (2 mmol) in THF (10 mL), 9-BBN (0.5 M
solution in THF, 2.2 mmol) was added at room temperature
under an argon atmosphere, and the mixture was stirred for
1.5 h. Sodium methoxide (2.2 mmol) was added to the
mixture, and after stirring for 30 min, TMEDA (4.4 mmol)
and tert-BuLi (1.5 M solution in pentane, 4.4 mmol) were
added to the mixture at K20 8C. After stirring for 2 h, the
mixture was gradually raised to room temperature, and
stirred for 4 h. Then, electrophile (5 mmol) was added, and
the whole was stirred overnight (in the cases of alkyl halides)
or heated under reflux for 3 h (in the cases of p-allyl
palladium complexes). To the reaction mixture, 20% NaOH
(10 mL) and 30% H2O2 (2 mL) were added under ice-
cooling and the whole was stirred for 30 min. The mixture
was diluted with ethyl acetate (100 mL), washed with brine,
and dried over MgSO4. The solvent was removed, and the
residue was separated by MPLC to give 9 (with hexane/
AcOEtZ100:1–10:1) and 10 (with hexane/AcOEtZ1:1).
3.3.6. 11-Allyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]-
indole (9f). 1H NMR (CDCl3) d: 1.67–1.73 (m, 2H),
1.73–1.79 (m, 2H), 1.81–1.87 (m, 2H), 2.85 (t, 2H, JZ
5.2 Hz), 3.48 (td, 2H, JZ1.7, 6.3 Hz), 4.15 (t, 2H,
JZ5.8 Hz), 4.96 (qd, 1H, JZ1.5, 11.4 Hz), 5.03 (qd, 1H,
JZ1.5, 17.2 Hz), 5.96 (tdd, 1H, JZ6.3, 11.4, 17.2 Hz), 7.03
(t, 1H, JZ7.8 Hz), 7.13 (dt, 1H, JZ1.5, 7.8 Hz), 7.25 (d,
1H, JZ8.0 Hz), 7.50 (d, 1H, JZ8.0 Hz). 13C NMR (CDCl3)
d: 25.5, 27.9, 28.8, 29.6, 31.2, 44.6, 107.7, 108.4, 114.1,
118.4, 118.5, 120.5, 127.6, 135.8, 138.1, 139.6. HR-MS m/z:
Calcd for C16H19N: 225.1517. Found: 225.1526.
3.3.1. 9-Methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole
3.3.7. 2,3-Dihydro-1H-pyrrolo[1,2-a]indol-9-ylaceto-
nitrile (9g). Mp 99–100 8C (hexane). IR (CHCl3):
1
(9a). Mp 50–51 8C (lit.13 48–49 8C). H NMR (CDCl3) d:
1
2430 cmK1. H NMR (CDCl3) d: 2.55–2.65 (m, 2H), 3.03
2.24 (s, 3H), 2.52 (m, 2H), 2.88 (t, 2H, JZ7.3 Hz), 3.95 (t,
2H, JZ6.9 Hz), 7.00–7.12 (m, 2H), 7.15 (d, 1H, JZ7.8 Hz),
7.45 (d, 1H, JZ7.3 Hz). 13C NMR (CDCl3) d: 8.8, 22.7,
27.5, 43.3, 100.4, 108.7, 118.1, 119.8, 133.0, 132.4, 141.1.
MS m/z: 171 (MC).
(t, 2H, JZ7.3 Hz), 3.73 (s, 2H), 4.00 (t, 2H, JZ6.8 Hz),
7.11 (dt, 1H, JZ1.0, 7.8 Hz), 7.15 (dt, 1H, JZ1.0, 7.8 Hz),
7.21 (d, 1H, JZ7.8 Hz), 7.46 (d, 1H, JZ7.8 Hz). 13C NMR
(CDCl3) d: 13.5, 23.1, 27.5, 43.7, 93.4, 109.6, 117.5, 118.1,
119.3, 120.9, 130.9, 132.3, 142.5. MS m/z: 196 (MC). Anal.
Calcd for C13H12N2: C, 79.56; H, 6.16; N, 14.27. Found: C,
79.58; H, 6.25; N, 14.26.
3.3.2. 5-Methyl-6,7,8,9-tetrahydropyrido[1,2-a]indole
(9b). H NMR (CDCl3) d: 1.88–1.94 (m, 2H), 2.04–2.10
1
(m, 2H), 2.24 (s, 3H), 2.90 (t, 2H, JZ6.3 Hz), 4.03 (t, 2H,
JZ6.3 Hz), 7.11 (t, 1H, JZ7.8 Hz), 7.17 (t, 1H, JZ8.0 Hz),
7.25 (d, 1H, JZ8.0 Hz), 7.52 (d, 1H, JZ8.1 Hz). 13C NMR
(CDCl3) d: 8.2, 21.4, 22.5, 23.7, 42.4, 104.8, 108.4, 117.8,
119.0, 120.2, 128.6, 133.0, 136.0. HR-MS m/z: Calcd for
C13H15N: 185.1204. Found: 185.1192.
3.3.8. 6,7,8,9-Tetrahydropyrido[1,2-a]indol-10-ylaceto-
nitrile (9h). Mp 102–103 8C (hexane). IR (CHCl3):
2428 cmK1 1H NMR (CDCl3) d: 1.91–1.97 (m, 2H),
.
2.06–2.12 (m, 2H), 2.94 (t, 2H, JZ6.3 Hz), 3.74 (s, 3H),
4.04 (t, 2H, JZ6.3 Hz), 7.16 (t, 1H, JZ7.8 Hz), 7.19 (t, 1H,
JZ7.8 Hz), 7.28 (d, 1H, JZ8.0 Hz), 7.55 (d, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 12.7, 20.7, 22.3, 23.1, 42.3,
97.5, 108.9, 117.1, 118.2, 120.1, 121.1, 126.6, 134.6, 135.9.
3.3.3. 11-Methyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]-
indole (9c). Mp 88–89 8C (hexane). 1H NMR (CDCl3)

M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
1021
MS m/z: 210 (MC). Anal. Calcd for C14H14N2: C, 79.97; H,
6.71; N, 13.32. Found: C, 79.74; H, 6.74; N, 13.20.
120.9, 132.1, 132.6, 142.2, 148.1, 167.3. MS m/z: Calcd for
C16H17NO2: 255.1259. Found: 255.1258.
3.3.9. 7,8,9,10-Tetrahydro-6H-azepino[1,2-a]indol-
11-ylacetonitrile (9i). Mp 102–103 8C (hexane). IR
3.3.14. Methyl (2E)-4-(6,7,8,9-tetrahydropyrido[1,2-a]-
indol-10-yl)-but-2-enoate (9n). Mp 84–85 8C (hexane). IR
(CHCl3): 1710, 1654 cmK1. 1H NMR (CDCl3) d: 1.87–1.93
(m, 2H), 2.03–2.11 (m, 2H), 2.83 (t, 2H, JZ6.3 Hz), 3.57
(dd, 2H, JZ1.7, 6.3 Hz), 3.67 (s, 3H), 4.03 (t, 2H, JZ
6.3 Hz), 5.78 (td, 1H, JZ1.7, 15.5 Hz), 7.08 (t, 1H, JZ
7.8 Hz), 7.14 (t, 1H, JZ7.8 Hz), 7.25 (d, 1H, JZ8.0 Hz),
7.43 (d, 1H, JZ8.0 Hz). 13C NMR (CDCl3) d: 21.1, 22.4,
23.4, 26.9, 42.3, 51.4, 104.8, 108.6, 117.7, 119.4, 120.5,
120.6, 127.6, 134.0, 136.0, 148.0, 167.3. MS m/z: 269 (MC).
Anal. Calcd for C17H19NO2: C, 75.80; H, 7.11; N, 5.20.
Found: C, 75.71; H, 6.93; N, 5.11.
1
(CHCl3): 2430 cmK1. H NMR (CDCl3) d: 1.73–1.80 (m,
4H), 1.85–1.90 (m, 2H), 2.90 (t, 2H, JZ5.1 Hz), 3.78 (s, 3H),
4.17 (t, 2H, JZ5.1 Hz), 7.13 (t, 1H, JZ7.8 Hz), 7.20 (dt, 1H,
JZ1.5, 7.8 Hz), 7.28 (d, 1H, JZ8.0 Hz), 7.55 (d, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 13.1, 25.6, 27.4, 29.3, 31.0,
44.8, 98.6, 108.9, 117.6, 118.5, 119.5, 121.4, 126.4, 135.8,
140.6. MS m/z: 224 (MC). Anal. Calcd for C15H16N2: C,
80.32; H, 7.19; N, 12.49. Found: C, 80.22; H, 7.33; N, 12.35.
3.3.10. 9-Cyclohex-2-en-1-yl-2,3-dihydro-1H-pyrrolo-
[1,2-a]indole (9j). Mp 53–54 8C (hexane). 1H NMR
(CDCl3) d: 1.62–1.71 (m, 1H), 1.72–1.83 (m, 2H9),
1.96–2.04 (m, 1H), 2.08–2.14 (m, 2H), 2.52–2.60 (m, 2H),
2.91–3.03 (m, 2H), 3.66–3.71 (m, 1H), 4.01 (t, 2H, JZ
7.0 Hz), 5.83 (s, 1H), 7.01 (t, 1H, JZ7.8 Hz), 7.09 (t, 1H,
JZ7.8 Hz), 7.20 (d, 1H, JZ8.0 Hz), 7.55 (d, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 21.5, 24.1, 25.2, 27.7, 30.6,
32.7, 43.1, 109.1, 109.5, 118.2, 118.7, 119.9, 127.0, 131.0,
131.6, 132.3, 140.9. MS m/z: 237 (MC). Anal. Calcd for
C17H19NC1/10H2O: C, 85.38; H, 8.09; N, 5.85. Found: C,
85.30; H, 8.22; N, 5.90.
3.3.15. Methyl (2E)-4-(7,8,9,10-tetrahydro-6H-azepino-
[1,2-a]indol-11-yl)but-2-enoate (9o). IR (CHCl3):
1708 cmK1 1H NMR (CDCl3) d: 1.66–1.72 (m, 2H),
.
1.74–1.80 (m, 2H), 1.83–1.90 (m, 2H), 2.82 (t, 2H, JZ
5.2 Hz), 3.61 (dd, 2H, JZ1.7, 6.3 Hz), 3.67 (s, 3H), 4.16 (t,
2H, JZ4.6 Hz), 5.75 (dt, 1H, JZ1.7, 15.5 Hz), 7.05 (t, 1H,
JZ8.0 Hz), 7.11 (dt, 1H, JZ6.3, 15.5 Hz), 7.17 (t, 1H, JZ
8.0 Hz), 7.25 (d, 1H, JZ8.0 Hz), 7.42 (d, 1H, JZ7.8 Hz).
13C NMR (CDCl3) d: 25.6, 27.3, 27.9, 29.5, 31.2, 42.0, 51.4,
105.6, 108.6, 118.1, 118.8, 120.7, 120.8, 127.4, 136.0,
140.2, 148.7, 167.4. MS m/z: Calcd for C18H21NO2:
283.1572. Found: 283.1570.
3.3.11.
rel-(9aR,10S)-10-Cyclohex-2-en-1-yl-9a-(9-
oxa-10-borabicyclo[3.3.2]dec-10-yl)-6,7,8,9,9a,10-hexa-
hydropyrido[1,2-a]indole (9k). Mp 209–210 8C (hexane/
AcOEt). 1H NMR (CDCl3) d: 0.74–0.83 (m, 1H), 1.30–2.10
(m, 24H), 2.40 (dd, 1H, JZ2.8, 5.1 Hz), 2.91 (d, 1H, JZ
2.8 Hz), 3.51 (dt, 1H, JZ2.8, 13.4 Hz), 3.60 (d, 1H, JZ
13.4 Hz), 4.80–4.86 (m, 1H), 5.63 (d, 1H, JZ10.3 Hz), 5.72
(td, 1H, JZ1.8, 10.3 Hz), 6.48 (d, 1H, JZ7.5 Hz), 6.54 (t,
1H, JZ7.5 Hz), 6.99 (d, 1H, JZ6.9 Hz), 7.05 (t, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 21.1, 21.6, 22.1, 22.6, 23.6,
24.7, 24.8, 26.9, 27.1, 31.4, 33.9, 40.2, 43.9, 56.9, 67.6,
74.3, 108.2, 116.2, 126.2, 127.3, 128.7, 130.8, 131.8, 152.8.
MS m/z: 388, 389 (MC). Anal. Calcd for C26H36BNOC1/
4H2O: C, 79.28; H, 9.34; N, 3.55. Found: C, 79.03; H, 9.35;
N, 3.53.
3.3.16. (2E)-4-(2,3-Dihydro-1H-pyrrolo[1,2-a]indol-9-
1
yl)but-2-en-1-ol (9p). IR (CHCl3): 3612 cmK1. H NMR
(CDCl3) d: 2.55–2.65 (m, 2H), 2.93 (t, 2H, JZ7.5 Hz), 3.46
(d, 2H, JZ6.9 Hz), 4.03 (t, 2H, JZ6.8 Hz), 4.09 (br s, 2H),
5.71–5.78 (m, 1H), 5.90 (ttd, 1H, JZ1.2, 6.3, 15.5 Hz), 7.03
(dt, 1H, JZ1.0, 7.8 Hz), 7.10 (dt, 1H, JZ1.0, 7.8 Hz), 7.20
(d, 1H, JZ8.0 Hz), 7.48 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 23.3, 27.7, 43.4, 63.4, 103.1, 109.2, 118.5, 120.3,
129.0, 131.6, 132.2, 132.5, 141.5. HR-MS m/z: Calcd for
C15H17NO: 227.1310. Found: 227.1305.
3.3.17. (2E)-4-(6,7,8,9-Tetrahydro-1H-pyrido[1,2-a]-
indol-10-yl)but-2-en-1-ol (9q). IR (CHCl3): 3612 cmK1
.
1H NMR (CDCl3) d: 1.86–1.93 (m, 2H), 2.03–2.10 (m, 2H),
2.87 (t, 2H, JZ6.9 Hz), 3.44 (d, 2H, JZ6.3 Hz), 4.03 (t, 2H,
JZ6.3 Hz), 4.07 (br s, 2H), 5.65–5.74 (m, 1H), 5.80–5.88
(m, 1H), 7.07 (t, 1H, JZ8.0 Hz), 7.13 (t, 1H, JZ8.0 Hz),
7.24 (d, 1H, JZ8.0 Hz), 7.44 (d, 1H, JZ7.8 Hz). 13C NMR
(CDCl3) d: 21.2, 22.5, 23.5, 26.9, 63.8, 107.1, 108.6, 117.9,
119.2, 120.3, 127.8, 128.8, 131.9, 133.4, 136.0. HR-MS m/z:
Calcd for C16H19NO: 241.1466. Found: 241.1466.
3.3.12. 11-Cyclohex-2-en-1-yl-7,8,9,10-tetrahydro-6H-
azepino[1,2-a]indole (9l). Mp 94–95 8C (hexane). 1H
NMR (CDCl3) d: 1.62–1.94 (m, 10H), 2.09–2.25 (m, 2H),
2.83–2.93 (m, 2H), 3.63–3.70 (m, 1H), 4.09–4.19 (m, 2H),
5.79 (d, 1H, JZ10.3 Hz), 5.85 (td, 1H, JZ2.3, 9.7 Hz), 6.99
(t, 1H, JZ8.0 Hz), 7.10 (t, 1H, JZ8.0 Hz), 7.24 (d, 1H, JZ
8.4 Hz), 7.63 (d, 1H, JZ7.8 Hz). 13C NMR (CDCl3) d: 23.0,
25.2, 25.4, 28.2, 29.5, 31.2, 31.7, 33.7, 44.4, 108.4, 114.0,
118.1, 119.4, 120.2, 126.9, 127.0, 132.5, 135.8, 139.0. MS
m/z: 265 (MC). Anal. Calcd for C19H23NC1/10H2O: C,
85.40; H, 8.75; N, 5.24. Found: 85.24; H, 8.72; N, 5.16.
3.3.18. (2E)-4-(7,8,9,10-Tetrahydro-6H-azepino[1,2-a]-
indol-11-yl)but-2-en-1-ol (9r). IR (CHCl3): 3612 cmK1
.
1H NMR (CDCl3) d: 1.65–1.91 (m, 6H), 2.85 (t, 2H, JZ
5.7 Hz), 3.48 (d, 2H, JZ5.7 Hz), 4.06 (d, 2H, JZ6.3 Hz),
4.15 (t, 2H, JZ4.6 Hz), 5.64–5.71 (m, 1H), 5.84 (td, 1H,
JZ5.7, 15.1 Hz), 7.04 (t, 1H, JZ7.8 Hz), 7.14 (t, 1H,
JZ7.8 Hz), 7.25 (d, 1H, JZ8.0 Hz), 7.49 (d, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 25.6, 27.2, 28.0, 29.6, 31.2,
44.6, 63.6, 107.9, 108.5, 118.4, 118.6, 120.6, 127.5, 128.7,
132.5, 135.9, 139.6. HR-MS m/z: Calcd for C17H12NO:
255.1623. Found: 255.1612.
3.3.13. Methyl (2E)-4-(2,3-dihydro-1H-pyrrolo[1,2-a]-
indol-9-yl)but-2-enoate (9m). IR (CHCl3): 1710,
1
1648 cmK1. H NMR (CDCl3) d: 2.50–2.65 (m, 2H), 2.92
(t, 2H, JZ7.5 Hz), 3.60 (d, 2H, JZ6.3 Hz), 3.69 (s, 3H),
4.04 (t, 2H, JZ6.8 Hz), 5.84 (td, 1H, JZ1.8, 15.4 Hz), 7.05
(t, 1H, JZ7.8 Hz), 7.10–7.19 (m, 2H), 7.21 (d, 1H, JZ
8.0 Hz), 7.43 (d, 1H, JZ8.0 Hz). 13C NMR (CDCl3) d: 23.3,
27.8, 27.9, 43.7, 51.4, 100.9, 109.5, 118.3, 118.9, 120.4,

1022
M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
3.3.19. rel-(1R,4S)-4-(2,3-Dihydro-1H-pyrrolo[1,2-a]-
indol-9-yl)cyclohex-2-en-1-yl acetate (9s). Mp 101–02 8C
JZ8.0 Hz), 7.63 (d, 1H, JZ7.8 Hz). 13C NMR (CDCl3) d:
23.4, 30.2, 32.4, 46.4, 62.7, 101.0, 109.4, 119.3, 121.1,
121.4, 127.9, 128.7, 136.0. HR-MS m/z: Calcd for
C13H17NO: 203.1310. Found: 203.1295.
(hexane/AcOEt). IR (CHCl3): 1720 cmK1 1H NMR
.
(CDCl3) d: 1.86–1.94 (m, 1H), 1.94–2.00 (m, 1H), 2.09 (s,
3H), 2.55–2.65 (m, 2H), 2.99 (t, 2H, JZ7.3 Hz), 3.60–3.66
(m, 2H), 4.02 (t, 2H, JZ7.3 Hz), 5.30–5.36 (m, 1H), 5.88
(ddd, 1H, JZ2.4, 4.0, 10.0 Hz), 6.10 (dd, 1H, JZ2.4,
10.0 Hz), 7.04 (t, 1H, JZ7.8 Hz), 7.11 (t, 1H, JZ7.8 Hz),
7.21 (d, 1H, JZ8.0 Hz), 7.54 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 21.4, 24.2, 26.2, 27.4, 27.8, 32.9, 43.2, 67.5,
107.9, 109.3, 118.5, 118.6, 120.2, 125.1, 131.5, 132.5,
136.8, 141.1, 170.8. MS m/z: 295 (MC). Anal. Calcd for
C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.02; H,
7.12; N, 4.49.
3.4. General procedure for the preparation of 13, 14
and 17
The reaction using 11 was carried out according to the
procedure for the prepatation of 8. Hydroboration of 11b
with 9-BBN was effected under reflux for 2 h.
3.4.1. 2-Methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole
(13a). Mp 58–59 8C (hexane/AcOEt). H NMR (CDCl3)
1
d: 1.29 (d, 3H, JZ6.9 Hz), 2.63 (dd, 1H, JZ6.9, 15.9 Hz),
3.04–3.14 (m, 1H), 3.19 (dd, 1H, JZ8.0, 15.9 Hz), 3.62 (dd,
1H, JZ6.3, 9.7 Hz), 4.22 (dd, 1H, JZ7.4, 9.7 Hz), 6.15 (s,
1H), 7.05 (dt, 1H, JZ1.0, 7.8 Hz), 7.11 (td, 1H, JZ1.0,
7.8 Hz), 7.21 (d, 1H, 8.0 Hz), 7.54 (d, 1H, JZ8.0 Hz). 13C
NMR (CDCl3) d: 19.7, 33.0, 37.3, 50.9, 92.6, 109.3, 119.1,
120.2, 120.3, 132.8, 132.9, 144.2. MS m/z: 171 (MC). Anal.
Calcd for C12H13N: C, 84.17; H, 7.65; N, 8.18. Found: C,
84.15; H, 7.64; N, 8.16.
3.3.20.
9-(Tetrahydrofuran-2-yl)-2,3-dihydro-1H-
pyrrolo[1,2-a]indole (9t). Mp 72–73 8C (hexane/AcOEt).
1H NMR (CDCl3) d: 2.00–2.20 (m, 3H), 2.22–2.30 (m, 1H),
2.56–2.62 (m, 2H), 2.99–3.11 (m, 2H), 3.88–3.94 (m, 1H),
4.02 (t, 2H, JZ6.9 Hz), 4.06–4.12 (m, 1H), 5.16 (t, 1H, JZ
7.4 Hz), 7.05 (t, 1H, JZ8.0 Hz), 7.11 (t, 1H, JZ8.0 Hz),
7.20 (d, 1H, JZ8.0 Hz), 7.59 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 24.2, 26.6, 27.4, 43.5, 68.0, 75.4, 106.7, 109.5,
119.0, 119.4, 120.4, 131.1, 132.9, 141.8. MS m/z: 227 (MC).
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16.
Found: C, 79.05; H, 7.68; N, 5.99.
3.4.2. 2-Phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole
(13b). 1H NMR (CDCl3) d: 3.17 (dd, 1H, JZ7.5,
15.9 Hz), 3.50 (dd, 1H, JZ8.0, 15.9 Hz), 4.09 (dd, 1H,
JZ6.8, 9.9 Hz), 4.15–4.22 (m, 1H), 4.51 (dd, 1H, JZ8.1,
9.9 Hz), 6.27 (s, 1H), 7.13 (t, 1H, JZ7.8 Hz), 7.18 (t, 1H,
JZ7.8 Hz), 7.26–7.33 (m, 4H), 7.35–7.40 (m, 2H), 7.63 (d,
1H, JZ8.0 Hz). 13C NMR (CDCl3) d: 33.3, 47.9, 51.1, 93.0,
109.5, 119.4, 120.5, 120.6, 127.1, 127.2, 129.0, 132.9,
133.2, 142.9, 143.6. HR-MS m/z: Calcd for C17H15N:
233.1204. Found: 233.1210.
3.3.21. 3-(1H-Indol-1-yl)propan-1-ol (10a). IR (CHCl3):
3616 cmK1. 1H NMR (CDCl3) d: 1.56 (br s, 1H), 2.03–2.10
(m, 2H), 3.58 (t, 2H, JZ5.7 Hz), 4.28 (t, 2H, JZ6.8 Hz),
6.51 (d, 1H, JZ2.9 Hz), 7.09–7.15 (m, 2H), 7.22 (t, 1H, JZ
7.8 Hz), 7.39 (d, 1H, JZ8.0 Hz), 7.64 (d, 1H, JZ8.0 Hz).
13C NMR (CDCl3) d: 32.7, 42.7, 59.6, 101.2, 109.4, 119.4,
121.1, 121.5, 128.0, 128.7, 136.1. HR-MS m/z: Calcd for
C11H13NO: 175.0997. Found: 175.0982.
3.4.3. 3-(1H-Indol-1-yl)-2-methylpropan-1-ol (14a). IR
(CHCl3): 3624 cmK1. 1H NMR (CDCl3) d: 0.97 (d, 3H, JZ
6.9 Hz), 1.37 (br s, 1H), 2.20–2.29 (m, 1H), 3.49 (d, 2H, JZ
4.0 Hz), 3.99 (dd, 1H, JZ6.9, 14.3 Hz), 4.24 (dd, 1H, JZ
6.9, 14.3 Hz), 7.17–7.12 (m, 2H), 7.20 (t, 1H, JZ8.0 Hz),
7.38 (d, 1H, JZ8.0 Hz), 7.63 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 15.0, 36.9, 49.0, 65.1, 101.2, 109.6, 119.3, 121.0,
121.5, 128.6, 136.4. HR-MS m/z: Calcd for C12H15NO:
189.1154. Found: 189.1153.
3.3.22. 3-(5-Nitro-1H-indol-1-yl)propan-1-ol (10b). Mp
1
85 8C (hexane/AcOEt). IR (CHCl3): 3628 cmK1. H NMR
(CDCl3) d: 1.57 (br s, 1H), 2.03–2.12 (m, 2H), 3.61 (t, 2H,
JZ6.3 Hz), 4.34 (t, 2H, JZ6.9 Hz), 6.68 (d, 1H, JZ
2.3 Hz), 7.28 (d, 1H, JZ2.3 Hz), 7.41 (d, 1H, JZ9.0 Hz),
8.10 (dd, 1H, JZ1.7, 8.6 Hz), 8.58 (d, 1H, JZ1.7 Hz). 13C
NMR (CDCl3) d: 32.6, 43.1, 59.0, 104.1, 109.3, 117.3,
118.3, 127.7, 131.2, 139.0, 141.6. MS m/z: 220 (MC). Anal.
Calcd for C11H12N2O3: C, 59.99; H, 5.49; N, 12.72. Found:
C, 59.76; H, 5.51; N, 12.89.
3.4.4. 3-(1H-Indol-1-yl)-2-phenylindole (14b). IR
(CHCl3): 3624 cmK1 1H NMR (CDCl3) d: 1.42 (br s,
.
1H), 3.31–3.38 (m, 1H), 3.78 (br s, 2H), 4.33 (dd, 1H, JZ
6.9, 14.4 Hz), 4.59 (dd, 1H, JZ8.0, 14.4 Hz), 6.42 (d, 1H,
JZ3.5 Hz), 6.92 (d, 1H, JZ3.5 Hz), 7.10 (t, 1H, JZ
7.8 Hz), 7.18–7.23 (m, 3H), 7.25–7.31 (m, 1H), 7.31–7.39
(m, 3H), 7.62 (d, 1H, JZ8.0 Hz). 13C NMR (CDCl3) d:
48.3, 48.7, 64.1, 101.3, 109.5, 119.5, 121.1, 121.6, 127.5,
128.1, 128.5, 128.7, 129.0, 136.2, 139.9. HR-MS m/z: Calcd
for C17H17NO: 251.1301. Found: 231.1304.
3.3.23. 4-(1H-Indol-1-yl)butan-1-ol (10c). IR (CHCl3):
1
3624 cmK1. H NMR (CDCl3) d: 1.50–1.55 (m, 2H), 1.68
(br s, 1H), 1.87–1.94 (m, 2H), 3.59 (t, 2H, JZ6.3 Hz), 4.15
(t, 2H, JZ6.8 Hz), 6.55 (d, 2H, JZ2.9 Hz), 7.09–7.14 (m,
2H), 7.22 (t, 1H, JZ8.0 Hz), 7.36 (d, 1H, JZ8.0 Hz), 7.64
(d, 1H, JZ7.8 Hz). 13C NMR (CDCl3) d: 26.8, 30.1, 46.2,
62.3, 101.1, 109.5, 119.4, 121.1, 121.5, 127.9, 128.7, 136.0.
HR-MS m/z: Calcd for C12H15NO: 189.1154. Found:
189.1166.
3.4.5. 1-Allyl-1,3-dihydro-2H-indol-2-one (17). IR (neat):
1708 cmK1. 1H NMR (CDCl3) d: 3.55 (s, 2H), 4.34 (dt, 2H,
JZ5.1, 1.5 Hz), 5.21 (dd, 1H, JZ1.0, 10.3 Hz), 5.23 (dd,
1H, JZ1.0, 17.1 Hz), 5.84 (tdd, 1H, JZ5.1, 10.3, 17.1 Hz),
6.81 (d, 1H, JZ7.8 Hz), 7.02 (dt, 1H, JZ1.0, 7.8 Hz), 7.23
(t, 1H, JZ7.8 Hz), 7.24 (d, 1H, JZ8.0 Hz). 13C NMR
(CDCl3) d: 35.7, 42.2, 108.9, 117.5, 122.3, 124.3, 124.4,
3.3.24. 5-(1H-Indol-1-yl)pentan-1-ol (10d). IR (CHCl3):
3620 cmK1 1H NMR (CDCl3) d: 1.35–1.40 (m, 2H),
.
1.53–1.60 (m, 2H), 1.83–1.90 (m, 2H), 3.60 (t, 2H, JZ
6.3 Hz), 4.13 (t, 2H, JZ6.8 Hz), 6.49 (d, 1H, JZ2.9 Hz),
7.08–7.12 (m, 2H), 7.21 (t, 1H, JZ8.0 Hz), 7.34 (d, 1H,

M. Ishikura et al. / Tetrahedron 62 (2006) 1015–1024
1023
127.7, 131.4, 144.3, 174.7. HR-MS m/z: Calcd for
C11H11NO: 173.0840. Found: 173.0822.
mixture was gradually raised to room temperature, and
stirred for 4 h. To the reaction mixture, allyl bromide
(605 mg, 5 mmol) was added and the mixture was stirred at
room temperature overnight. The mixture was diluted with
ethyl acetate (100 mL), washed with brine, and dried over
MgSO4. The solvent was removed, and the residue was
separated by MPLC (hexane/AcOEtZ100:1) to give 22
(232 mg, 35%).
3.5. Procedure for the preparation of 9a, 20, 10e and 21
from 18
Conversion of 18a to 9a (40%) and 10a (13%) was carried
out according to the procedure for the preparation of 8.
Mp 127–128 8C (hexane/AcOEt). 1H NMR (CDCl3) d:
0.03 (br s, 1H), 0.71 (br s, 1H), 1.22 (s, 3H), 1.15–1.35
(m, 1H), 1.38–1.88 (m, 13H), 2.03 (dd, 1H, JZ7.4,
12.6 Hz), 2.10–2.20 (m, 1H), 2.29 (dd, 1H, JZ9.7,
13.2 Hz), 2.64 (td, 1H, JZ2.3, 13.2 Hz), 3.06 (dt, 1H,
JZ6.8, 11.4 Hz), 3.35 (t, 1H, JZ9.7 Hz), 5.12 (d, 1H, JZ
10.1 Hz), 5.16 (d, 1H, JZ17.2 Hz), 5.96 (dtd, 1H, JZ4.6,
10.1, 17.2 Hz), 6.98 (dd, 1H, JZ1.7, 8.3 Hz), 7.05 (dd,
1H, JZ1.7, 7.8 Hz), 7.10–7.17 (m, 2H). 13C NMR
(CDCl3) d: 21.0, 23.4, 24.1, 26.6, 26.8, 31.6, 31.9, 32.7,
33.7, 43.1, 48.7, 52.1, 117.2, 117.9, 123.1, 125.7, 126.8,
136.7, 146.6, 148.2. MS m/z: 332, 333 (MC). Anal. Calcd
for C23H32BN: C, 82.87; H, 9.67; N, 4.20. Found: C,
82.74; H, 9.77; N, 4.16.
Reaction using 18b was effected as follows: to a solution of
18b (430 mg, 2 mmol) in THF (10 mL), 9-BBN (0.5 M
solution in THF, 2.2 mmol) was added at room temperature
under an argon atmosphere, and the mixture was stirred for
1.5 h. Sodium methoxide (118 mg, 2.2 mmol) was added to
the mixture, and after stirring for 30 min, LDA (4.4 mmol)
was added to the mixture at K78 8C. After stirring for 1 h, the
mixture was gradually raised to room temperature, and stirred
for 4 h. To the reaction mixture, 20% NaOH (10 mL) and 30%
H2O2 (2 mL) were added under ice-cooling and the whole was
stirred for 30 min. The mixture was diluted with ethyl acetate
(100 mL), washed with brine, and dried over MgSO4. The
solvent was removed, and the residue was separated by MPLC
to give 20 (69 mg, 16%) (with hexane/AcOEtZ50:1) and 21
(47 mg, 10%) (with hexane/AcOEtZ1:1).
3.5.1. 3-(1H-3-Methylindol-1-yl)propan-1-ol (10e). IR
Acknowledgements
1
(CHCl3): 3624 cmK1. H NMR (CDCl3) d: 2.01–2.07 (m,
2H), 2.32 (s, 3H), 3.58–3.63 (m, 2H), 4.21 (t, 2H, JZ
6.3 Hz), 6.88 (s, 1H), 7.09 (t, 1H, JZ7.8 Hz), 7.19 (t, 1H,
JZ7.8 Hz), 7.33 (d, 1H, JZ8.0 Hz), 7.56 (d, 1H, JZ
8.0 Hz). 13C NMR (CDCl3) d: 9.6, 32.8, 42.3, 59.7, 109.1,
110.4, 118.6, 119.1, 121.4, 125.6, 128.8, 136.4. HR-MS m/z:
Calcd for C12H15NO: 189.1154. Found: 189.1142.
This was supported in part by ‘Academic Frontier’ Project
for Private University: matching fund subsidy from Ministry
of Education, Culture, Sports, Science and Technology,
2002–2006.
References and notes
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carboxylate (20). Mp 92–93 8C (hexane). IR (neat):
1
1686 cmK1. H NMR (CDCl3) d: 2.61–2.70 (m, 2H), 3.29
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(t, 2H, JZ7.5 Hz), 3.89 (s, 3H), 4.11 (t, 2H, JZ5.8 Hz),
7.18–7.28 (m, 3H), 8.09 (d, 1H, JZ8.0 Hz). 13C NMR
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.
(CDCl3) d: 1.65 (br s, 1H), 2.03–2.11 (m, 2H), 3.60 (t,
2H, JZ5.8 Hz), 3.90 (s, 3H), 4.32 (t, 2H, JZ6.3 Hz), 7.25–
7.29 (m, 2H), 7.39–7.42 (m, 1H), 8.15–8.19 (m, 1H). 13C
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