A synthetic use of the intramolecular alkyl migration process in indolylborates for intramolecular cyclization: A novel construction of carbazole derivatives

Article abstract of DOI:10.1016/S0040-4020(02)01293-0

The intramolecular alkyl migration reaction in indolylborates was developed for the one-pot construction of carbazoles via intramolecular cyclization in which π-allylpalladium complexes were successfully adopted as an acceptor for the indole nucleophile.

Full text of DOI:10.1016/S0040-4020(02)01293-0

Tetrahedron 58 (2002) 9827–9838
A synthetic use of the intramolecular alkyl migration process
in indolylborates for intramolecular cyclization:
a novel construction of carbazole derivatives
*
Minoru Ishikura and Hiromi Kato
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Received 23 August 2002; accepted 3 October 2002
Abstract—The intramolecular alkyl migration reaction in indolylborates was developed for the one-pot construction of carbazoles via
intramolecular cyclization in which p-allylpalladium complexes were successfully adopted as an acceptor for the indole nucleophile. q 2002
Elsevier Science Ltd. All rights reserved.
The indole framework has been widely accepted as a pivotal
structure with representatives in numerous natural isolates
and medicinal agents, and, therefore, indole derivatives
have been for a long time the target of synthetic chemists.1
In connection with our project directed toward the synthetic
applications of heteroarylboron compounds,2 we have
recently been developing a new access to indole derivatives
based on indolylborates 2, an example of which showed that
a cross-coupling protocol using indolylborate was of
apparent value in indole alkaloid synthesis.3
An intramolecular 1,2-alkyl migration from boron to carbon
Scheme 1.
Keywords: indolylborate; intramolecular alkyl migration; palladium catalyst; carbazoles.
*
Corresponding author. Tel./fax: þ81-1332-3-1245; e-mail: ishikura@hoku-iryo-u.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01293-0

9828
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
Scheme 2.
in trialkylalkenylborate has been well identified as a useful
protocol for carbon–carbon bond formation,4 and the alkyl
migration process has been also shown to be successful in
furan-, pyrrole-, indole-, and pyridine-substituted borane
compounds.5 Recently, we have embarked upon extending
the scope of this migration process in indolylborate 2 to an
intramolecular cyclization enabling the one-pot construc-
tion of poly-cyclic indole derivatives, and these results are
reported in this paper.6
As depicted in Scheme 1, we envisioned that an alkyl
migration triggered by an intramolecular nucleophilic attack
of the C-3 of the indole ring on the electrophilic site (X) in
indolylborate C might provide the cyclization product E via
Table 1. Reaction of indolylborates (2) with p-allylpalladium complexes
2
Allyl esters vinyl epoxide
3
Yield (%)
3a–g
2a
2b
3a
3b
75
70
(R0¼Me, E¼–CH2CHvCH2)
(R0¼H, E¼–CH2CHvCH2)
2a
2b
3c
75
73
(R0¼Me, E¼
(R0¼H, E¼
)
3d
)
2a
3e
60
(R0¼Me, E¼
)
2a
2b
3f
60
58
(R0¼Me, E¼
(R0¼H, E¼
)
3g
)

M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
9829
Scheme 3.
D in a one-pot manner. However, there are restrictions in
that the precursor of electrophilic site (X) must be left intact
in both the hydroboration of A with dialkylborane (borane
formation) and the reaction of 2-lithioindole with B (borate
formation). Also, the precursor (X) must be feasibly labile
toward the indole nucleophile in the alkyl migration-
cyclization steps (from C to D). Thus, we speculated that
allyl ester could favorably withstand both the borane and
borate formations, and that a p-allylpalladium complex
carried by the oxidative addition of an allyl ester to the
palladium (0) compound is an activated form capable of
accepting the indole nucleophile in the cyclization step.
Simply, to a THF solution of indolylborate 2a generated
from indole 1a,7 allyl acetate (1.5 equiv.) and PdCl2(Ph3P)2
(5 mol%) were added, and the mixture was heated at 608C
under an argon atmosphere. The reaction proceeded
successfully to give 3-allyl-2-ethyl-1-methylindole 3a, in
which the ethyl group migrated from boron to carbon (C2 of
the indole) at the opposite side from the nucleophilic
approach (C3 of the indole) to p-allylpalladium com-
plexes.8 Otherwise, 3b was the product from the reaction of
2b, generated from 1b,7 with allyl acetate in the presence
of PdCl2(Ph3P)2, accompanied by the elimination of the
OMe group (Scheme 2). As summarized in Table 1, various
p-allylpalladium complexes, carried from allyl acetates and
vinyl epoxide with a catalytic amount of PdCl2(Ph3P)2,
exerted sufficient electrophilicity toward the indole
nucleophile, giving rise to 3 in good yields.
Thus, our study commenced with an intermolecular reaction
of allyl acetate with indolylborates 2 in the presence of a
catalytic amount of palladium complex in order to show the
availability of p-allyl-palladium complexes as electrophiles
in the alkyl migration step.
Subjection of indolylborates 2c–f with sterically encumbered
Scheme 4.

9830
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
Scheme 5.
trialkylboryl groups [(sec-butyl)3B, and 4] to the alkyl
migration reaction with allyl acetate in the presence of
PdCl2(Ph3P)2 was also effective in producing indoles 3h–m
in modest to good yields (Scheme 3).
the intramolecular coordination of the oxygen of Boc group
to boron (Scheme 4). Borane 5 was resistant to conventional
oxidation with H2O2 under basic conditions at 08C even
after the elongation of the reaction time.
Otherwise, treating indolylborate 2g (derived from indole
1c),7 which contained a weak electron-withdrawing Boc
group at the 1-position of the indole ring, with allyl acetate
in the presence of PdCl2(PPh3P)2 allowed the isolation of
alkylborane 5 (38% yield), which is stable possibly owing to
Having established the availability of p-allylpalladium
complexes as electrophiles capable of promoting the
intramolecular alkyl migration, we next sought to extend
this protocol to the intramolecular cyclization process in a
one-pot manner from indoles 1. Thus, indolylborates 9 were

M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
9831
Table 2. Formation of 10 through intramolecular cyclization
Formation of 10a was also observed from the cyclization
reaction of 9g, which can be interpreted by adopting the
cascade of alkyl-boryl migration that was reported in our
previous paper10 (Scheme 5, Table 2).
9
PdLn
Yield of 10a (%)
9a
9b
9b
9c
9d
9d
9e
9f
Pd(Ph3P)4
Pd(Ph3P)4
10a (56)
10b (27)
10b (56)
10c (40)
10d (26)
10d (23)
10e (40)
10f (25)
10f (34)
10a (6)
Pd2(dba)3·CHCl3þ4Ph3P
Hydroboration of ester 12 in THF (derived from commer-
cially available aldehyde 11 via conventional chemical
transformations) brought about alkylborane 13 in situ, and
the subsequent treatment of 2-lithioindoles, carried from
1a,b, with 13 generated indolylborates 14 that were
subjected to the cyclization reaction. However, the desired
products 15 were not isolated in these reactions and only
small amounts of 2-alkylindoles 16 were obtained through a
simple 1,2-alkyl migration reaction on quenching the
reaction. Inspection of the molecular model revealed that
the inefficiency of the cyclization using 14 could be due to
significant spatial repulsion between the Me group and the
9-BBN ring that is present in intermediate F (Scheme 6).
Pd(Ph3P)4
Pd(Ph3P)4
Pd2(dba)3·CHCl3þ4Ph3P
Pd(Ph3P)4
Pd(Ph3P)4
9f
9g
9g
Pd2(dba)3·CHCl3þ4Ph3P
Pd(Ph3P)4
Pd2(dba)3·CHCl3þ4Ph3P
10a (13)
a
Yields (%) based on indoles (1).
initially exposed to the intramolecular cyclization reaction.
Allylalcohols 6, obtained by the reaction of allylmagnesium
and butenylmagnesium bromides with acrolein and
matacrolein,9 were converted to benzoates 7 through
treatment with PBr3, followed by heating with potassium
benzoate in acetnitrile.9 The requisite alkylboranes 8 were
generated in situ in THF by hydroboration of dienes 7 with
9-BBN, and the subsequent addition of 8 to a THF solution
of 2-lithioindoles derived from 1 generated indolylborates
9a–f in situ. Heating a mixture of 9a–f with a palladium
complex (10 mol%) at 608C in THF afforded the expected
carbazoles 10 through intramolecular alkyl migration
triggered by an intramolecular nucleophilic attack of the
C-3 of the indole ring on the p-allylpalladium complex.
Next, extension of the cyclization protocol to the construc-
tion of a tetracyclic framework in a one-pot manner was
examined. Ester 18 was obtained from the known ketone
1711 by reduction (NaBH4/CeCl3·7H2O) and subsequent
benzoylation (PhCOCl/Et3N). Hydroboration of 18 with
9-BBN led to alkylborane 19 in situ, and the subsequent
treatment of 19 with 2-lithio derivatives of 1a,b generated
indolylborates 20a,b in situ. Heating 20 with a catalytic
amount of Pd complex at 608C readily produced tetracyclic
indoles 21 (Scheme 7).
Scheme 6.

9832
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
Scheme 7.
The known ketone 2212 was converted to a mixture of
1,4-cis and trans isomers 23a,b by conventional methods
and the isomeric mixture was separated by MPLC. An initial
study, which was undertaken using a mixture of indolyl-
borates 25 derived from 2-lithio-1-methylindole and an
isomeric mixture of 24, in the presence of Pd(Ph3P)4
(10 mol%), afforded tetracyclic indole 26 as a single isomer,
whose structure has previously been determined by single
crystal X-ray analysis.6 Again, 26 was the sole product even
when the separate reactions by using 25a and 25b were
performed (Scheme 8). An attempted reaction with
indolylborate 25c derived from 2-lithio-1-methoxyindole
and 24b gave no isolable products, probably due to the
decomposition of the products during work-up and/or SiO2
column.
The cyclization reaction proceeds through the nucleophilic
attack of indole on the p-allylpalladium complex from the
Scheme 8.

M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
9833
Scheme 9.
opposite side of the palladium with a simultaneous alkyl
migration in an anti manner, the stereochemical require-
ment of which made the formation of 27 via complex H
unfavorable, possibly, due to steric repulsion.8 The sole
formation of 26 from the separate reactions of 25a and
25b is explicable given an isomerization between the
p-allylpalladium complexes G and H13 (Scheme 9).
s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet,
br¼broad. Medium pressure liquid chromatography
(MPLC) was performed on silica gel (Silica gel 60 N,
Kanto Chemical Co., Inc.). Dehydrated tetrahydrofuran
(THF) and diethyl ether (Et2O) were purchased from Kanto
Chemical Co., Inc.
1.1. General procedure for the intermolecular reaction
of indolylborates (2) with allyl acetates and vinyl epoxide
in the presence of PdCl2(PPh3)2
In summary, we were able to open a new, one-pot
intramolecular cyclization protocol for carbazole derivatives
based on the intramolecular alkyl migration reaction in
indolylborates 9, 14, 20, 25. Extension of the present protocol
to the preparation of natural indole isolates is in progress.
To a solution of indolylborates (2) generated from indoles
(1) (2 mmol) and trialkylboranes (2.4 mmol) in THF (10 ml)
in situ under an argon atmosphere,7 allyl esters (3 mmol) or
vinyl epoxide (3 mmol) and palladium complex (0.1 mmol)
were added, and the mixture was heated at 608C for 1 h.
After cooling, 10% NaOH (10 ml) and 30% H2O2 (5 ml)
were added under ice-cooling, and the whole was stirred for
10 min. The mixture was diluted with AcOEt (100 ml),
washed with brine, and dried over MgSO4. The solvent was
removed, and the residue was separated by MPLC with
hexane/AcOEt as an eluent to give 3.
1. Experimental
Melting points were recorded on a Yamato MP21. All
melting points and boiling points are uncorrected. MS and
high-resolution MS were recorded on a Micromass Auto-
Spec 3100 mass spectrometer. IR spectra were measured on
a Hitachi Model 270-30 spectrometer. The NMR experi-
ments were performed with a JEOL JNM-LA300 or
JNM-EX400 spectrometer, and chemical shifts are
expressed in ppm (d) with tetramethylsilane (TMS) as an
internal reference. The following abbreviations are used:
1.1.1. 2-Ethyl-1-methyl-3-(prop-2-enyl)indole (3a). IR
1
(neat): 1614 cm21. H NMR (CDCl3) d: 1.19 (t, 3H, J¼
7.3 Hz), 2.75 (q, 2H, J¼7.3 Hz), 3.48 (ddd, 2H, J¼1.5, 3.5,

9834
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
6.5 Hz), 3.67 (s, 3H), 4.97 (ddd, 1H, J¼1.5, 3.5, 10.3 Hz),
5.06 (ddd, 1H, J¼2, 3.5, 17.1 Hz), 5.98 (tdd, 1H, J¼6.5,
10.3, 17.1 Hz), 7.06 (dt, 1H, J¼1, 7.3 Hz), 7.13 (dt, 1H, J¼
2, 8.3 Hz), 7.22 (d, 1H, J¼8.3 Hz), 7.50 (d, 1H, J¼7.8 Hz).
13C NMR (CDCl3) d: 14.5, 17.6, 28.9, 29.1, 107.9, 108.6,
114.1, 118.3, 118.8, 120.6, 127.7, 136.8, 138.0, 138.8.
HR-MS m/z: Calcd for C14H17N: 199.1361. Found: 199.1362.
6.9, 7.3 Hz), 7.13 (d, 1H, J¼7.3 Hz), 7.45 (d, 1H, J¼
7.8 Hz). 13C NMR (CDCl3) d: 14.4, 17.4, 27.0, 29.0, 62.9,
107.7, 108.4, 117.9, 118.5, 120.4, 127.4, 128.6, 131.5,
136.4, 138.5. HR-MS m/z: Calcd for C15H19NO: 229.1466.
Found: 229.1466
1.1.7. (2E)-4-(2-Ethylindol-3-yl)but-2-en-1-ol (3g). IR
(neat): 3412 cm21 1H NMR (CDCl3) d: 1.20 (t, 3H,
.
1.1.2. 3-Allyl-2-ethylindole (3b). IR (neat): 3412 cm21. 1H
NMR (CDCl3) d: 1.22 (t, 3H, J¼7.8 Hz), 2.70 (q, 2H, J¼
7.8 Hz), 3.44 (dd, 2H, J¼1.7, 6.4 Hz), 4.97 (d, 1H, J¼
10.3 Hz), 5.05 (d, 1H, J¼17.1 Hz), 5.91–6.03 (m, 1H),
7.03–7.12 (m, 2H), 7.22 (d, 1H, J¼8.3 Hz), 7.49 (d, 1H,
J¼7.3 Hz), 7.70 (br s, 1H). 13C NMR (CDCl3) d: 14.2, 19.3,
28.5, 108.3, 110.3, 114.3, 118.3, 119.1, 120.9, 128.7, 135.2,
137.1, 137.6. HR-MS m/z: Calcd for C13H15N: 185.1205.
Found: 185.1211.
J¼7.3 Hz), 1.87 (br s, 1H), 2.66 (q, 2H, J¼7.3 Hz), 3.41 (d,
2H, J¼5.9 Hz), 3.97 (d, 2H, J¼5.4 Hz), 5.54–5.66 (m, 1H),
5.74–5.84 (m, 1H), 7.02–7.12 (m, 2H), 7.19 (d, 1H, J¼
7.5 Hz), 7.46 (d, 1H, J¼7.5 Hz), 7.91 (br s, 1H). 13C NMR
(CDCl3) d: 14.3, 19.3, 26.9, 63.4, 108.2, 110.4, 118.2, 119.0,
120.9, 128.5, 128.7, 131.8, 135.2, 137.2. HR-MS m/z: Calcd
for C14H17NO: 215.1310. Found: 215.1308.
1.1.8. 3-Allyl-2-(sec-butyl)-1-methylindole (3h). IR (neat):
1
1638, 1610 cm21. H NMR (CDCl3) d: 0.87 (t, 3H, J¼
1.1.3. 3-(Cyclohex-2-enyl)-2-ethyl-1-methylindole (3c).
Mp 65–668C (from AcOEt/hexane). IR (CHCl3):
7.3 Hz), 1.37 (d, 3H, J¼7.3 Hz), 1.69–1.89 (m, 2H), 3.01–
3.12 (m, 1H), 3.53 (td, 2H, J¼1.5, 5.9 Hz), 3.72 (s, 3H), 4.97
(dd, 1H, J¼2.1, 10 Hz), 5.04 (dd, 1H, J¼2.1, 10 Hz), 5.96
(tdd, 1H, J¼5.9, 10.2, 17.1 Hz), 7.06 (t, 1H, J¼7.8 Hz), 7.15
(t, 1H, J¼8.3 Hz), 7.25 (d, 1H, J¼8.3 Hz), 7.50 (d, 1H,
J¼7.8 Hz). 13C NMR (CDCl3) d: 12.9, 20.0, 29.1, 30.6,
33.0, 108.6, 114.2, 118.3, 118.7, 120.6, 128.2, 136.9, 138.0,
140.6. HR-MS m/z: Calcd for C16H21N: 227.1674. Found:
227.1677.
1
2932 cm21. H NMR (CDCl3) d: 1.20 (t, 3H, J¼7.3 Hz),
1.68–1.80 (m, 1H), 1.84–1.97 (m, 3H), 2.08–2.28 (m, 2H),
2.80 (q, 2H, J¼7.3 Hz), 3.60–3.66 (m, 1H), 3.67 (s, 3H),
5.75–5.81 (m, 1H), 5.83–5.90 (m, 1H), 7.01 (dt, 1H, J¼1.5,
7.6 Hz), 7.13 (dt, 1H, J¼1.5, 7.6 Hz), 7.25 (d, 1H, J¼
8.3 Hz), 7.64 (d, 1H, J¼8.3 Hz). 13C NMR (CDCl3) d: 15.0,
17.6, 23.0, 25.0, 29.1, 31.4, 33.8, 108.6, 114.1, 118.3, 119.4,
120.3, 126.8, 126.9, 132.3, 136.7, 138.1. MS m/z: 239 (Mþ).
Anal. Calcd for C17H21N: C, 85.31; H, 8.84; N, 5.85. Found:
C, 85.36; H, 9.00; N, 5.79.
1.1.9. 3-Allyl-2-(sec-butyl)indole (3i). IR (neat): 3240 cm21
.
1H NMR (CDCl3) d: 0.86 (t, 3H, J¼7.3 Hz), 1.29 (d, 3H,
J¼6.8 Hz), 1.56–1.74 (m, 2H), 2.92–3.03 (m, 1H), 3.46 (td,
2H, J¼1.5, 6.3 Hz), 4.98 (ddd, 1H, J¼1.5, 3.5, 10.1 Hz),
5.06 (ddd, 1H, J¼1.5, 3.5, 17.1 Hz), 5.97 (tdd, 1H, J¼6.3,
10.1, 17.1 Hz), 7.06 (dd, 1H, J¼1.5, 7.3 Hz), 7.11 (ddd, 1H,
J¼1.5, 7.4, 7.8 Hz), 7.29 (d, 1H, J¼7.8 Hz), 7.51 (d, 1H,
J¼7.3 Hz), 7.74 (br s, 1H). 13C NMR (CDCl3) d: 12.5, 20.7,
28.6, 30.0, 32.6, 108.6, 110.3, 114.3, 118.4, 119.0, 120.9,
128.7, 135.3, 137.8, 140.0. HR-MS m/z: Calcd for C15H19N:
213.1517. Found: 213.1506.
1.1.4. 3-(Cyclohex-2-enyl)-2-ethylindole (3d). Mp 109–
1
1108C (from AcOEt/hexane). IR (CHCl3): 3488 cm21. H
NMR (CDCl3) d: 1.23 (t, 3H, J¼7.5 Hz), 1.64–1.78 (m,
1H), 1.78–1.96 (m, 3H), 2.06–2.26 (m, 2H), 2.73 (q, 2H,
J¼7.7 Hz), 3.57–3.68 (m, 1H), 5.78 (d, 1H, J¼11.3 Hz),
5.82–5.89 (m, 1H), 7.02 (dt, 1H, J¼1.5, 6.8 Hz), 7.08 (dt,
1H, J¼1.5, 6.8 Hz), 7.21 (d, 1H, J¼7.8 Hz), 7.57–7.65 (m,
2H). 13C NMR (CDCl3) d: 14.7, 19.5, 22.8, 25.1, 31.0, 33.4,
110.3, 114.6, 118.7, 119.4, 120.7, 127.1, 127.9, 131.9,
135.3, 136.4. MS m/z: 225 (Mþ). Anal. Calcd for C16H19N:
C, 85.29; H, 8.50; N, 6.22. Found: C, 85.33; H, 8.44; N, 6.27.
1.1.10. 2-(sec-Butyl)-3-(cyclohex-2-enyl)-1-methylindole
(3j). IR (neat): 1736, 1470 cm21. 1H NMR (CDCl3) d: 0.88
(t, 3H, J¼7.3 Hz), 1.38 (d, 3H, J¼7.3 Hz), 1.65–1.85 (m,
3H), 1.85–2.00 (m, 3H), 2.08–2.30 (m, 2H), 3.06–3.20 (m,
1H), 3.67–3.78 (m, 1H), 3.72 (s, 3H), 5.72–5.80 (m, 1H),
5.81–5.88 (m, 1H), 7.00 (dt, 1H, J¼1.5, 7.3 Hz), 7.13 (dt,
1H, J¼1.5, 7.3 Hz), 7.23 (d, 1H, J¼7.8 Hz), 7.65 (d, 1H,
J¼7.8 Hz). 13C NMR (CDCl3) d: 12.9, 13.0, 20.2, 20.3,
23.2, 23.3, 25.1, 29.2, 30.7, 30.9, 31.0, 32.7, 32.8, 34.0,
108.6, 108.7, 114.9, 115.0, 118.2, 119.8, 120.4, 126.6,
126.7, 126.9, 127.0, 132.5, 132.6, 137.1, 137.2, 139.8,
139.9. HR-MS m/z: Calcd for C18H22N: 267.1987. Found:
269.1987.
1.1.5. Phenyl 5-(2-ethyl-1-methylindol-3-yl)-1,2,5,6-tetra-
hydropyridine-1-carboxylate (3e). IR (neat): 1720 cm21
.
1H NMR (CDCl3) d: 1.17 (t, 3H, J¼7.5 Hz), 2.75 (q, 2H,
J¼7.5 Hz), 3.26 and 3.47 (two d, 1H, J¼11.3 Hz), 3.55 (s,
3H), 3.85–4.10 (m, 2H), 4.20–4.30 (m, 1H), 4.41 and 4.52
(two d, 1H, J¼17.8 Hz), 5.80–5.90 (m, 1H), 6.00–6.10 (m,
1H), 6.95–7.18 (m, 5H), 7.21 (d, 1H, J¼7.8 Hz), 7.25–7.35
(m, 2H), 7.59 (d, 1H, J¼7.8 Hz). 13C NMR (CDCl3) d: 15.0,
17.7, 29.3, 33.3, 33.8, 43.7, 46.7, 47.6, 108.9, 109.2, 118.5,
118.7, 120.4, 121.4, 121.5, 122.9, 123.4, 124.9, 126.4,
129.1, 131.2, 131.5, 136.8, 139.2, 139.3, 151.4, 153.6,
153.9. HR-MS m/z: Calcd for C23H24N2O2: 360.1837.
Found: 360.1808.
1.1.11. 2-(sec-Butyl)-3-(cyclohex-2-enyl)indole (3k). IR
(neat): 3484, 1460 cm21. 1H NMR (CDCl3) d: 0.86 and 0.87
(two t, 3H, J¼7.5 Hz), 1.28 and 1.29 (two d, 3H, J¼7.5 Hz),
1.55–1.80 (m, 4H), 1.82–1.95 (m, 3H), 2.10–2.25 (m, 1H),
3.00–3.10 (m, 1H), 3.60–3.70 (m, 1H), 5.65–6.00 (m, 2H),
7.01 (t, 1H, J¼7.8 Hz), 7.08 (t, 1H, J¼8.3 Hz), 7.27 (d, 1H,
J¼8.3 Hz), 7.63 (d, 1H, J¼7.8 Hz), 7.69 (br s, 1H). 13C
NMR (CDCl3) d: 12.3, 12.4, 18.8, 21.1, 21.4, 23.0, 24.8,
25.1, 28.3, 30.1, 30.2, 31.0, 31.1, 32.4, 33.4, 33.5, 68.2,
1.1.6. (2E)-4-(2-Ethyl-1-methylindol-3-yl)but-2-en-1-ol
1
(3f). IR (neat): 3368 cm21. H NMR (CDCl3) d: 1.12 (t,
3H, J¼7.5 Hz), 2.28 (br s, 1H), 2.65 (q, 2H, J¼7.5 Hz), 3.39
(d, 2H, J¼6.4 Hz), 3.50 (s, 3H), 3.88 (d, 2H, J¼5.9 Hz),
5.55 (td, 1H, J¼5.9, 15.3 Hz), 5.73 (td, 1H, J¼5.9, 15.3 Hz),
7.01 (ddd, 1H, J¼1.5, 6.9, 7.8 Hz), 7.08 (ddd, 1H, J¼1.5,

M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
9835
110.4, 114.9, 118.5, 119.6, 119.7, 120.6, 125.6, 126.9,
127.0, 127.7, 132.2, 132.3, 132.7, 135.4, 138.9, 139.0.
HR-MS m/z: Calcd for C18H23N: 253.1831. Found:
253.1815.
over MgSO4. The solvent was removed, and the residue was
separated by MPLC with hexane/AcOEt¼50:1 as an eluent
to give 10, 15, 21, and 26.
1.2.1. 2E-Hexa-2,5-dienyl benzoate (7a). Bp 1158C/
1 mmHg. IR (neat): 1720 cm21 1H NMR (CDCl3) d:
.
1.1.12. 3-Allyl-2-(3,3-diethoxypropyl)-1-methylindole
(3l). IR (neat): 3484, 1460 cm21
.
1H NMR (CDCl3) d:
2.75–2.90 (m, 2H), 4.78 (dd, 2H, J¼1.5, 6.5 Hz), 5.03 (d,
1H, J¼10.5 Hz), 5.08 (d, 1H, J¼16.3 Hz), 5.73 (ddd, 1H,
J¼1.5, 6.5, 16.3 Hz), 5.76–5.90 (m, 2H), 7.25 (d, 1H, J¼
8.3 Hz), 7.42 (dd, 2H, J¼7.8, 8.3 Hz), 8.05 (dd, 2H, J¼1.5,
7.8 Hz). 13C NMR (CDCl3) d: 36.0, 65.1, 115.6, 124.9,
128.0, 129.3, 130.1, 133.2, 135.5, 165.9. HR-MS m/z: Calcd
for C13H14O2: 202.0994. Found: 202.1002.
1.21 (dt, 6H, J¼1.5, 7.1 Hz), 1.80–1.90 (m, 2H), 2.82 (t,
2H, J¼7.8 Hz), 3.43–3.53 (m, 4H), 3.64 (s, 3H), 3.60–3.70
(m, 2H), 4.48 (t, 1H, J¼5.4 Hz), 4.97 (dd, 1H, J¼1.5,
10.3 Hz), 5.05 (td, 1H, J¼1.5, 17.1 Hz), 5.97 (dtdd, 1H,
J¼1.5, 5.8, 10.3, 17.1 Hz), 7.05 (t, 1H, J¼7.8 Hz), 7.14 (t,
1H, J¼8.3 Hz), 7.22 (d, 1H, J¼8.3 Hz), 7.50 (d, 1H,
J¼7.8 Hz). 13C NMR (CDCl3) d: 15.4, 19.5, 28.9, 29.5,
33.8, 61.3, 102.1, 108.7, 114.3, 118.4, 118.8, 120.7, 127.7,
136.6, 136.8, 137.8. HR-MS m/z: Calcd for C19H27NO2:
301.2042. Found: 301.2039.
1.2.2. 2E-Hepta-2,6-dienyl benzoate (7b). Bp 1208C/
1 mmHg. IR (neat): 1720 cm21 1H NMR (CDCl3) d:
.
2.13–2.24 (m, 4H), 4.77 (d, 2H, J¼6.3 Hz), 4.98 (dd, 1H,
J¼2.0, 10.1 Hz), 5.03 (dd, 1H, J¼2.0, 17.3 Hz), 5.66–5.76
(m, 1H), 5.76–5.95 (m, 2H), 7.44 (dd, 2H, J¼7.8, 8.3 Hz),
7.55 (dd, 1H, J¼1.5, 7.8 Hz), 8.05 (dd, 2H, J¼1.5, 8.3 Hz).
13C NMR (CDCl3) d: 31.6, 33.0, 65.5, 115.0, 124.5, 128.3,
129.6, 130.5, 132.8, 135.4, 137.7, 166.2. MS m/z: 218 (Mþ).
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46. Found: C,
77.57; H, 7.53.
1.1.13. 3-Allyl-2-(3,3-diethoxypropyl)indole (3m). IR
(neat): 3404 cm21 1H NMR (CDCl3) d: 1.23 (t, 6H,
.
J¼7.3 Hz), 1.95 (q, 2H, J¼7.3 Hz), 2.79 (t, 2H, J¼7.3 Hz),
3.42–3.53 (m, 4H), 3.62–3.71 (m, 2H), 4.51 (t, 1H, J¼
5.5 Hz), 4.98 (dd, 1H, J¼1.9, 10.1 Hz), 5.05 (dd, 1H, J¼1.9,
17.3 Hz), 5.97 (tdd, 1H, J¼6.3, 10.1, 17.3 Hz), 7.05 (dt, 1H,
J¼1.5, 7.8 Hz), 7.10 (dt, 1H, J¼1.5, 8.3 Hz), 7.24 (d, 1H,
J¼8.3 Hz), 7.49 (d, 1H, J¼7.8 Hz), 8.30 (br s, 1H). 13C
NMR (CDCl3) d: 15.3, 21.0, 28.5, 33.2, 61.4, 102.2, 108.9,
110.4, 114.4, 118.4, 119.0, 121.0, 128.6, 135.1, 135.3,
137.6. HR-MS m/z: Calcd for C18H25NO2: 287.1885.
Found: 287.1884.
1.2.3. (2E)-2,4-Dimethylhexa-2,5-dienyl benzoate (7c).
Bp 1158C/1 mmHg. IR (neat): 1720 cm21
.
1H NMR
(CDCl3) d: 1.75, 1.82 and 1.87 (three s, 3H), 2.48–2.63
(m, 0.5H), 2.81–2.94 (m, 1.5H), 4.74 and 4.84 (two s, 2H),
4.90–5.15 (m, 2H), 5.48 and 5.60 (two t, 1H, J¼7.3 Hz),
5.74–5.88 (m, 1H), 7.44 (t, 1H, J¼7.8 Hz), 7.48 (t, 1H,
J¼7.8 Hz), 7.56 and 7.62 (two td, 1H, J¼1.5, 7.8 Hz), 8.06
and 8.11 (two dd, 1H, J¼1.5, 8.3 Hz). 13C NMR (CDCl3) d:
14.0, 18.5, 21.5, 32.0, 32.1, 37.4, 63.5, 64.3, 113.0, 115.0,
117.7, 126.4, 126.7, 128.3, 128.5, 129.6, 130.2, 130.3,
130.5, 131.2, 131.4, 132.9, 133.4, 133.7, 136.2, 136.6,
142.7, 165.7, 166.4. HR-MS m/z: Calcd for C14H16O2:
216.1150. Found: 216.1152.
1.1.14. tert-Butyl rel-(2S,3R)-3-allyl-2-diethylboranyl-2-
ethyl-2,3-dihydroindole-1-carboxylate (5). Mp 75–778C
1
(from hexane). IR (CHCl3): 1570 cm21. H NMR (CDCl3)
d: 0.29–0.41 (m, 1H), 0.56–0.67 (m, 3H), 0.70 (t, 3H,
J¼7.3 Hz), 0.76 (t, 3H, J¼7.3 Hz), 0.85 (t, 3H, J¼7.3 Hz),
1.45–1.58 (m, 1H), 1.62 (s, 9H), 1.72–1.83 (m, 1H), 2.27
(td, 1H, J¼9.3, 14.2 Hz), 2.50–2.59 (m, 1H), 2.99 (dd, 1H,
J¼5.4, 10.3 Hz), 5.00 (d, 1H, J¼16.6 Hz), 5.05 (d, 1H,
J¼10.3 Hz), 5.87–5.99 (m, 1H), 6.98 (dt, 1H, J¼1.5, 7 Hz),
7.17 (t, 1H, J¼7.8 Hz), 7.20 (dd, 1H, J¼1, 7.3 Hz), 7.27 (d,
1H, J¼7.8 Hz). 13C NMR (CDCl3) d: 8.5, 9.7, 9.9, 10.2,
13.4, 28.4, 32.2, 39.7, 48.4, 68.5, 87.0, 113.4, 116.0, 123.6,
126.4, 127.1, 138.1, 138.7, 140.7, 158.2. MS m/z: 355 (Mþ).
Anal. Calcd for C22H34NO2B: C, 74.37; H, 9.65; N, 3.94.
Found: C, 74.47; H, 9.69; N, 4.03.
1.2.4. 9-Methyl-4-vinyl-2,3,4,9-tetrahydro-1H-carbazole
(10a). Mp 61–638C (from AcOEt/hexane). IR (CHCl3):
1632, 1612 cm21. 1H NMR (CDCl3) d: 1.65–1.80 (m, 1H),
1.80–1.90 (m, 1H), 1.90–2.10 (m, 2H), 2.60–2.80 (m, 2H),
3.60–3.70 (m, 1H), 3.62 (s, 3H), 5.07 (dd, 1H, J¼1.5,
9.5 Hz), 5.13 (dd, 1H, J¼1.5, 17.1 Hz), 5.96 (ddd, 1H,
J¼7.5, 9.5, 17.1 Hz), 7.02 (dt, 1H, J¼1.5, 7.8 Hz), 7.13 (dt,
1H, J¼1.5, 7.8 Hz), 7.24 (d, 1H, J¼8.3 Hz), 7.53 (d, 1H,
J¼8.3 Hz). 13C NMR (CDCl3) d: 20.3, 22.1, 28.8, 30.0,
37.5, 108.5, 110.1, 114.1, 118.5, 118.8, 120.4, 127.1, 135.9,
136.8, 142.3. MS m/z: 211 (Mþ). Anal. Calcd for C15H17N:
C, 85.26; H, 8.11; N, 6.63. Found: C, 85.35; H, 7.90; N,
6.72.
1.2. General procedure for the intramolecular
cyclization reaction using indolylborates (9, 14, 20, 25)
To a solution of dienes (7, 12, 18, 23) (3 mmol) in THF
(5 ml) at room temperature under an argon atmosphere,
9-BBN (0.5 M solution in THF, 6 ml, 3 mmol) was added,
and the whole was stirred for 1 h. The resulted solution of
alkylboranes (8, 13, 19, 24) was added to a solution of
2-lithioindoles [generated from indoles (1) (2 mmol) and
tert- or n-BuLi (2.4 mmol) in THF (10 ml) under an argon
atmosphere],7 generating indolylborates (9, 14, 20, 25) in
situ. The mixture was heated with palladium complex
(0.1 mmol) at 608C for 2 h. After cooling, 10% NaOH
(10 ml) and 30% H2O2 (5 ml) were added under ice-cooling,
and the mixture was stirred for 10 min. The mixture was
diluted with AcOEt (100 ml), washed with brine, and dried
1.2.5. 4-Vinyl-2,3,4,9-tetrahydro-1H-carbazole (10b). IR
(neat): 3412 cm21. 1H NMR (CDCl3) d: 1.65–1.85 (m, 2H),
1.88–1.99 (m, 2H), 2.55–2.70 (m, 2H), 3.55–3.65 (m, 1H),
5.05 (dd, 1H, J¼1.5, 10.3 Hz), 5.11 (d, 1H, J¼17.1 Hz),
5.94 (ddd, 1H, J¼7.3, 10.3, 17.1 Hz), 7.03 (t, 1H, J¼
7.3 Hz), 7.10 (t, 1H, J¼7.3 Hz), 7.18 (d, 1H, J¼7.8 Hz),
7.51 (d, 1H, J¼7.8 Hz), 7.57 (br s, 1H). 13C NMR (CDCl3)
d: 20.4, 23.2, 30.4, 37.6, 110.3, 110.9, 114.2, 118.9, 119.0,
120.8, 127.6, 135.7, 142.4. HR-MS m/z: Calcd for C14H15N:
197.1205. Found: 197.1208.

9836
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
1.2.6. 5-Methyl-10-vinyl-5,6,7,8,9,10-hexahydrocyclo-
hepta[b]indole (10c). Mp 58–598C (from EtOH). IR
1.2.11. (2Z)-2,4-Dimethyl-6-(1-methylindol-2-yl)hex-2-
enyl benzoate (16a). IR (neat): 1718 cm21 1H NMR
.
1
(CHCl3): 1632, 1610 cm21. H NMR (CDCl3) d: 1.53–
(CDCl3) d: 0.98 (d, 3H, J¼6.8 Hz), 1.31–1.43 (m, 1H),
1.43–1.55 (m, 1H), 1.58–1.74 (m, 2H), 1.75 (s, 3H), 2.42–
2.54 (m, 1H), 2.70 (t, 2H, J¼7.5 Hz), 3.60 (s, 3H), 4.70 (s,
2H), 5.33 (d, 1H, J¼10.3 Hz), 6.22 (s, 1H), 7.05 (dt, 1H,
J¼1, 7.8 Hz), 7.14 (dt, 1H, J¼1, 8.3 Hz), 7.22 (d, 1H, J¼
8.3 Hz), 7.40 (t, 2H, J¼7.8 Hz), 7.48–7.56 (m, 2H), 8.04 (d,
2H, J¼7.8 Hz). 13C NMR (CDCl3) d: 14.3, 20.9, 26.6, 26.9,
29.3, 32.2, 37.1, 70.7, 98.7, 108.7, 119.2, 119.7, 120.4,
127.9, 128.3, 129.0, 129.6, 130.4, 132.8, 135.9, 137.3,
141.4, 166.4. HR-MS m/z: Calcd for C25H29NO2: 375.2198.
Found: 375.2196.
1.65 (m, 1H), 1.82–1.93 (m, 3H), 1.96–2.05 (m, 1H), 2.07–
2.15 (m, 1H), 2.75 (ddd, 1H, J¼2.7, 11.5, 15.7 Hz), 2.94
(ddd, 1H, J¼2.7, 6.6, 15.7 Hz), 3.67 (s, 3H), 3.96–4.01 (m,
1H), 4.78 (td, 1H, J¼1.7, 16.6 Hz), 4.98 (td, 1H, J¼1.7,
10.2 Hz), 6.03 (ddd, 1H, J¼5.9, 10.2, 16.6 Hz), 7.05 (dt, 1H,
J¼1, 5, 7.8 Hz), 7.13 (dt, 1H, J¼1.5, 8.3 Hz), 7.23 (d, 1H,
J¼8.3 Hz), 7.45 (d, 1H, J¼7.8 Hz). 13C NMR (CDCl3) d:
25.6, 25.8, 27.2, 29.5, 33.2, 38.8, 108.7, 113.6, 114.1, 117.6,
118.7, 120.4, 127.9, 136.1, 138.0, 140.9. MS m/z: 225 (Mþ).
Anal. Calcd for C16H19N: C, 85.28; H, 8.50; N, 6.22. Found:
C, 85.00; H, 8.50; N, 6.23.
1.2.12. (2Z)-2,4-Dimethyl-6-(indol-2-yl)hex-2-enyl benzo-
ate (16b). IR (neat): 3404, 1706 cm21. 1H NMR (CDCl3) d:
0.95 (d, 3H, J¼6.8 Hz), 1.22–1.35 (m, 1H), 1.40–1.50 (m,
1H), 1.60–1.75 (m, 2H), 1.73 (s, 3H), 2.40–2.50 (m, 1H),
2.71 (dt, 2H, J¼2.9, 7.3 Hz), 4.68 (d, 1H, J¼12.2 Hz), 4.74
(d, 1H, J¼12.2 Hz), 5.30 (d, 1H, J¼9.7 Hz), 6.21 (s, 1H),
7.03–7.13 (m, 2H), 7.28 (d, 1H, J¼7.3 Hz), 7.41 (t, 2H,
J¼7.8 Hz), 7.48–7.57 (m, 2H), 8.06 (d, 2H, J¼8.3 Hz),
8.08 (br s, 1H). 13C NMR (CDCl3) d: 14.2, 20.9, 27.0, 28.2,
32.1, 36.8, 70.8, 99.5, 110.4, 119.5, 119.7, 120.8, 128.4,
128.8, 128.9, 129.6, 130.4, 132.9, 135.8, 139.8, 166.6. HR-
MS m/z: Calcd for C24H27NO2: 361.2042. Found: 361.2041.
1.2.7. 10-Vinyl-5,6,7,8,9,10-hexahydrocyclohepta[b]-
1
indole (10d). IR (neat): 3408 cm21. H NMR (CDCl3) d:
1.45–1.63 (m, 1H), 1.78–2.02 (m, 4H), 2.06–2.19 (m, 1H),
2.70–2.80 (m, 1H), 2.80–2.92 (m, 1H), 3.90–4.00 (m, 1H),
4.76 (td, 1H, J¼1.9, 16.6 Hz), 4.99 (td, 1H, J¼1.5, 9.7 Hz),
6.01 (ddd, 1H, J¼5.8, 10.3, 16.8 Hz), 7.03–7.12 (m, 2H),
7.26 (dd, 1H, J¼1.5, 7.3 Hz), 7.44 (d, 1H, J¼7.3 Hz), 7.70
(br s, 1H). 13C NMR (CDCl3) d: 25.7, 27.5, 29.1, 33.6, 38.7,
110.2, 113.8, 114.3, 117.7, 119.1, 120.8, 129.4, 134.4,
137.3, 140.8. HR-MS m/z: Calcd for C15H17N: 211.1361.
Found: 211.1343.
1.2.8. 4-Isopropenyl-9-methyl-2,3,4,9-tetrahydro-1H-
carbazole (10e). Mp 88–908C (from hexane). IR
1.2.13. Preparation of 2-allylcyclohex-2-enyl benzoate
(18). To a mixture of 1711 (2 g, 15 mmol) and CeCl3·7H2O
(6.7 g, 18 mmol) in MeOH (100 ml), NaBH4 (570 mg,
15 mmol) was added portionwise under ice-cooling. After
stirring for 30 min at rt, the mixture was concentrated on
rotary evaporator. The residue was diluted with AcOEt
(100 ml), washed brine, and dried over MgSO4. The solvent
was removed, and the residue was separated by MPLC with
hexane/AcOEt (10:1) as an eluent to give 1.8 g (87%) of
2-allylcyclohex-2-enol.
1
(CHCl3): 1642 cm21. H NMR (CDCl3) d: 1.71 (s, 3H),
1.74–1.95 (m, 3H), 1.98–2.07 (m, 1H), 2.70 (t, 2H, J¼
5.9 Hz), 3.61 (s, 3H), 3.62–3.68 (m, 1H), 4.77–4.80 (m,
1H), 4.86–4.90 (m, 1H), 7.01 (dt, 1H, J¼1.5, 7.3 Hz), 7.12
(dt, 1H, J¼1.5, 7.8 Hz), 7.24 (d, 1H, J¼7.8 Hz), 7.48 (d, 1H,
J¼7.8 Hz). 13C NMR (CDCl3) d: 20.0, 21.1, 22.2, 29.0,
29.1, 41.7, 108.3, 110.4, 112.0, 118.6, 118.8, 120.3, 127.1,
136.5, 136.8, 148.5. MS m/z: 225 (Mþ). Anal. Calcd for
C16H19N: C, 85.28; H, 8.50; N, 6.22. Found: C, 85.27; H,
8.63; N, 6.24.
1
Colorless oil. IR (neat): 3324 cm21. H NMR (CDCl3) d:
1.53 (br s, 1H), 1.55–1.62 (m, 1H), 1.62–1.69 (m, 1H),
1.69–1.73 (m, 1H), 1.73–1.82 (m, 1H), 1.91–2.02 (m, 1H),
2.80–2.94 (m, 2H), 4.03–4.12 (m, 1H), 5.03–5.13 (m, 2H),
5.58 (t, 1H, J¼3.7 Hz), 5.86 (tdd, 1H, J¼6.8, 10.8, 17.1 Hz).
13C NMR (CDCl3) d: 17.9, 25.4, 32.0, 38.8, 66.7, 115.9,
126.1, 136.9, 137.6. HR-MS m/z: Calcd for C9H14O:
138.1045. Found: 138.1042.
1.2.9. 4-Isopropenyl-2,3,4,9-tetrahydro-1H-carbazole
(10f). Mp 113–1148C (from EtOH). IR (CHCl3):
1
3476 cm21. H NMR (CDCl3) d: 1.71 (s, 3H), 1.74–1.86
(m, 2H), 1.89–2.05 (m, 2H), 2.64–2.80 (m, 2H), 3.59–3.68
(m, 1H), 4.75–4.81 (m, 1H), 4.85–4.91 (m, 1H), 7.02 (dt,
1H, J¼1.5, 7.5 Hz), 7.09 (dt, 1H, J¼1.5, 7.5 Hz), 7.26 (d,
1H, J¼7.8 Hz), 7.47 (d, 1H, J¼7.8 Hz), 7.70 (br s, 1H). 13C
NMR (CDCl3) d: 19.9, 21.2, 23.3, 29.3, 41.5, 110.2, 111.3,
112.0, 118.9, 119.0, 120.8, 127.7, 134.9, 135.7, 148.4. MS
m/z: 211 (Mþ). Anal. Calcd for C15H17N: C, 85.26; H, 8.11;
N, 6.63. Found: C, 85.24; H, 8.20; N, 6.62.
Benzoyl chloride (1.68 g, 10 mmol) was added to a solution
of 2-allylcyclohex-2-enol (1.38 g, 10 mmol) and triethyl-
amine (2.02 g, 20 mmol) in CH2Cl2 (200 ml) under ice-
cooling, and the whole was stirred for 1 h. The mixture was
concentrated on rotary evaporator. The residue was diluted
with ether (100 ml), washed with water, and dried over
MgSO4. The solvent was removed, and the residue was
separated by MPLC with hexane/AcOEt (40:1) as an eluent
to 1.8 g (74%) of 18.
1.2.10. (2E)-2-Methylhexa-2,5-dienyl benzoate (12). Bp
1108C/1 mmHg. IR (neat): 1718 cm21. 1H NMR (CDCl3) d:
0.98 (d, 3H, J¼6.8 Hz), 1.74 (s, 3H), 2.05 (t, 2H, J¼6.8 Hz),
2.49 and 2.52 (two q, 1H, J¼6.8 Hz), 4.70 (s, 2H), 4.98 (d,
1H, J¼10.2 Hz), 5.00 (d, 1H, J¼17.1 Hz), 5.34 and 5.79
(two s, 1H), 5.74 and 5.76 (two ddd, 1H, J¼6.8, 10.2,
17.1 Hz), 7.43 (t, 2H, J¼7.8 Hz), 7.54 (t, 1H, J¼7.8 Hz),
8.05 (d, 2H, J¼8.3 Hz). 13C NMR (CDCl3) d: 14.2, 20.2,
32.2, 41.5, 70.5, 115.8, 128.3, 128.9, 129.5, 130.5, 132.8,
135.3, 136.8, 166.2. HR-MS m/z: Calcd for C16H20O2:
244.1463. Found: 244.1456.
Bp 1428C/1 mmHg. IR (neat): 1716 cm21. 1H NMR (CDCl3)
d: 1.60–1.80 (m, 2H), 1.83–1.99 (m, 2H), 1.99–2.10 (m,
1H), 2.11–2.22 (m, 1H), 2.79 (d, 2H, J¼5.9 Hz), 4.97–5.00
(m, 1H), 5.02 (d, 1H, J¼4.4 Hz), 5.50–5.56 (m, 1H), 5.74–
5.86 (m, 2H), 7.42 (t, 2H, J¼7.8 Hz), 7.58 (t, 1H, J¼7.3 Hz),
8.06 (dd, 2H, J¼1.5, 8.3 Hz). 13C NMR (CDCl3) d: 18.3,

M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
9837
25.2, 29.0, 38.7, 69.7, 116.3, 128.2, 128.7, 129.6, 130.7,
132.7, 134.3, 135.9, 166.2. MS m/z: 242 (Mþ). Anal. Calcd
for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.12; H, 7.33.
(CDCl3) d: 1.48–1.59 (m, 1H), 1.73–1.90 (m, 2H), 2.10–
2.22 (m, 1H), 2.17 (d, 2H, J¼5.4 Hz), 5.06 (d, 1H, J¼
10.2 Hz), 5.08 (d, 1H, J¼17.1 Hz), 5.45 (dd, 1H, J¼4.3,
7.5 Hz), 5.82 (tdd, 1H, J¼7.5, 10.2, 17.1 Hz), 5.88 (dd, 1H,
J¼4.3, 10.2 Hz), 5.94 (d, 2H, J¼10.2 Hz), 7.43 (t, 2H,
J¼7.3 Hz), 7.54 (t, 1H, J¼7.3 Hz), 8.05 (d, 2H, J¼7.3 Hz).
13C NMR (CDCl3) d: 24.4, 27.5, 35.3, 39.7, 67.7, 116.4,
125.0, 128.3, 129.6, 130.8, 132.7, 136.4, 137.4, 166.1.
HR-MS m/z: Calcd for C16H18O2: 242.1307. Found:
242.1323.
1.2.14. 8-Methyl-1,2,3,5,6,7,8,12c-octahydrobenzo[3,4]-
cyclohepta[1,2-b]indole (21a). Mp 84–858C (from
.
EtOH). IR (CHCl3): 1610 cm21 1H NMR (CDCl3) d:
1.65 (ddd, 1H, J¼2.5, 10.2, 12.3 Hz), 1.70–1.95 (m, 4H),
2.05–2.25 (m, 4H), 2.24 (dd, 1H, J¼7.5, 13.3 Hz), 2.63
(ddd, 1H, J¼1.5, 5.4, 14.7 Hz), 3.06 (ddd, 1H, J¼6.4, 12.7,
14.7 Hz), 3.64 (s, 3H), 3.70–3.79 (m, 1H), 5.59 (d, 1H,
J¼2.9 Hz), 7.06 (t, 1H, J¼7.8 Hz), 7.13 (t, 1H, J¼7.8 Hz),
7.25 (d, 1H, J¼7.8 Hz), 7.56 (d, 1H, J¼7.8 Hz). 13C NMR
(CDCl3) d: 20.1, 22.8, 25.6, 27.8, 28.9, 31.3, 31.8, 38.2,
109.2, 113.0, 117.6, 118.6, 120.1, 123.5, 127.3, 135.4,
136.4, 139.3. MS m/z: 251 (Mþ). Anal. Calcd for C18H21N:
C, 86.01; H, 8.42; N, 5.57. Found: C, 86.09; H, 8.42; N,
5.43.
1.2.18. rel-(1S,4R)-4-Allylcyclohex-2-enyl benzoate
(23b). Bp 1478C/1 mmHg. IR (neat): 1714 cm21 1H
.
NMR (CDCl3) d: 1.36–1.46 (m, 1H), 1.68–1.78 (m, 1H),
1.90–1.99 (m, 1H), 2.00–2.23 (m, 3H), 2.23–2.34 (m, 1H),
5.05 (d, 1H, J¼10.2 Hz), 5.06 (d, 1H, J¼17.3 Hz), 5.51–
5.57 (m, 1H), 5.77–5.88 (m, 3H), 7.42 (t, 2H, J¼7.3 Hz),
7.54 (t, 1H, J¼7.3 Hz), 8.05 (dd, 2H, J¼1.5, 7.3 Hz). 13C
NMR (CDCl3) d: 26.2, 27.6, 34.9, 39.8, 70.0, 116.4, 126.5,
128.2, 129.6, 130.7, 132.7, 135.7, 136.3, 166.3. HR-MS m/z:
Calcd for C16H18O2: 242.1307. Found: 242.1325.
1.2.15. 1,2,3,5,6,7,8,12c-Octahydrobenzo[3,4]cyclohepta-
[1,2-b]indole (21b). Mp 122–1238C (from AcOEt/hexane).
1
IR (CHCl3): 3476 cm21. H NMR (CDCl3) d: 1.63–1.82
(m, 3H), 1.86–1.95 (m, 2H), 2.08–2.16 (m, 3H), 2.18–2.26
(m, 1H), 2.31 (td, 1H, J¼4.9, 12.7 Hz), 2.41 (td, 1H, J¼4.2,
14.1 Hz), 3.18 (td, 1H, J¼9.7, 15.1 Hz), 3.64–3.75 (m, 1H),
5.59–5.66 (m, 1H), 7.05–7.13 (m, 2H), 7.28 (dd, 1H, J¼
2.5, 5.9 Hz), 7.52 (dd, 1H, J¼2.5, 5.9 Hz), 7.62 (br s, 1H).
13C NMR (CDCl3) d: 22.4, 23.5, 25.7, 27.6, 31.0, 32.2, 38.2,
110.5, 113.2, 117.9, 119.0, 120.4, 124.0, 128.6, 134.0, 134.7,
138.9. MS m/z: 237 (Mþ). Anal. Calcd for C17H19N: C, 86.03;
H, 8.07; N, 5.90. Found: C, 86.14; H, 8.25; N, 5.70.
1.2.19. 8-Methyl-3,4,4a,5,6,7,8,12c-octahydrobenzo[3,4]-
cyclohepta[1,2-b]indole (26). Mp 129–1308C (from
1
AcOEt/hexane). IR (CHCl3): 1650, 1605 cm21. H NMR
(CDCl3) d: 1.35–1.50 (m, 2H), 1.50–1.75 (m, 3H), 1.90–
2.05 (m, 2H), 2.05–2.25 (m, 2H), 2.78 (ddd, 1H, J¼1.9,
11.8, 15.1 Hz), 2.98 (ddd, 1H, J¼2.5, 6.0, 15.1 Hz), 3.54 (br
s, 1H), 3.64 (s, 3H), 5.96–6.03 (m, 1H), 6.37 (d, 1H, J¼
10.3 Hz), 6.98 (dq, 1H, J¼1.5, 7.9 Hz), 7.09 (dq, 1H, J¼1.5,
7.9 Hz), 7.23 (d, 1H, J¼8.3 Hz), 7.90 (d, 1H, J¼8.3 Hz).
13C NMR (CDCl3) d: 24.5, 25.1, 27.2, 29.2, 31.8, 38.9, 40.6,
42.2, 108.9, 115.1, 118.4, 119.8, 119.9, 126.3, 126.7, 130.9,
136.1, 140.1. MS m/z: 251 (Mþ). Anal. Calcd for C18H21N:
C, 86.01; H, 8.42; N, 5.57. Found: C, 86.02; H, 8.57; N,
5.47.
1.2.16. Preparation of 4-allylcyclohex-2-enyl benzoate
(23). To a mixture of 2212 (2 g, 15 mmol) and CeCl3·7H2O
(6.7 g, 18 mmol) in MeOH (100 ml), NaBH4 (570 mg,
15 mmol) was added portionwise under ice-cooling. After
stirring for 30 min at rt, the mixture was concentrated on
rotary evaporator. The residue was diluted with AcOEt
(100 ml), washed brine, and dried over MgSO4. The solvent
was removed, and the residue was separated by MPLC with
hexane/AcOEt (7:1) as an eluent to give a 1,4-trans and cis
isomeric mixture of 4-allylcyclohex-2-enol (1.55 g, 75%).
Acknowledgements
This work was supported in part by a Grant-in Aid for
Scientific Research (No. 13672226) and for High
Technology Research Program from the Ministry of
Education, Culture, Sports, Science and Technology of
Japan.
1
Colorless oil. IR (neat): 3612 cm21. H NMR (CDCl3) d:
1.20–1.32 (m, 1H), 1.40–1.52 (m, 1H), 1.64 (br s, 1H),
1.70–1.80 (m, 1H), 1.80–1.89 (m, 1H), 1.97–2.13 (m, 2H),
2.13–2.22 (m, 1H), 4.17–4.25 (m, 1H), 4.99–5.08 (m, 2H),
5.66–5.73 (m, 2H), 5.73–5.83 (m, 1H). 13C NMR (CDCl3)
d: 26.6, 31.7, 35.0, 40.1, 66.7, 116.1, 130.7, 133.4, 136.4.
HR-MS m/z: C9H14O: 138.1045. Found: 138.1030.
References
1. (a) Sundberg, R. J. The Chemistry of Indoles. Academic:
London, 1970. (b) Sundberg, R. J. Indoles. Academic: San
Diego, 1996.
Benzoyl chloride (1.68 g, 12 mmol) was added to a solution
of 4-allylcyclohex-2-enol (1.38 g, 10 mmol) and triethyl-
amine (2.02 g, 20 mmol) in CH2Cl2 (200 ml) under ice-
cooling, and the whole was stirred for 1 h. The mixture was
concentrated on rotary evaporator. The residue was diluted
with ether (100 ml), washed with water, and dried over
MgSO4. The solvent was removed, and the residue was
separated by MPLC with hexane/AcOEt (40:1) as an eluent
to 360 mg (15%) of 23a and 1.1 g (45%) of 23b.
2. (a) Ishikura, M.; Agata, I. Recent Res. Dev. Org. Chem. 1997,
1, 145–157. (b) Ishikura, M. Curr. Org. Chem. 2002, 6,
507–521.
3. (a) Ishikura, M.; Hino, A.; Yaginuma, T.; Agata, I.; Katagiri,
N. Tetrahedron 2000, 56, 193–207. (b) Ishikura, M.;
Imaizumi, K.; Katagiri, N. Heterocycles 2000, 53,
2201–2220.
4. (a) Brown, H. C. Organic Synthesis via Boranes. Wiley: New
York, 1975. (b) Mikhailov, B. M.; Bubnov, Yu. N.
Organoboron Compounds in Organic Synthesis. Harwood
1.2.17. rel-(1S,4S)-4-Allylcyclohex-2-enyl benzoate (23a).
Bp 1478C/1 mmHg. IR (neat): 1712 cm21
.
1H NMR

9838
M. Ishikura, H. Kato / Tetrahedron 58 (2002) 9827–9838
Academic: London, 1983. (c) Negishi, E.; Idacavage, M. J.
Org. React. 1985, 33, 1–246.
9. Hwa, C. H.; Sims, H. Organic Synthesis, Wiley: New York,
1973; Coll. Vol. 5. pp 608–612.
10. Ishikura, M.; Kato, H.; Ohnuki, N. Chem. Commun. 2002,
220–221.
5. (a) Levy, A. B. J. Org. Chem. 1978, 43, 4684–4685.
(b) Marinelli, E. R.; Levy, A. B. Tetrahedron Lett. 1979,
2313–2316. (c) Sotoyama, T.; Hara, S.; Suzuki, A. Bull.
Chem. Soc. Jpn 1979, 52, 1865–1866. (d) Ishikura, M.; Ohta,
T.; Terashima, M. Heterocycles 1986, 24, 2793–2796.
(e) Terashima, M.; Ishikura, M. Adv. Heterocycl. Chem.
1989, 46, 143–167.
11. Conflone, P. N.; Baggiolini, E.; Hennessy, B.; Uskokovic,
M. R. J. Org. Chem. 1981, 46, 4923–4927.
12. Stork, G.; Danheiser, R. L. J. Org. Chem. 1973, 38,
1775–1776.
13. (a) Takahashi, K.; Jinbo, Y.; Kitamura, K.; Tsuji, J.
Tetrahedron Lett. 1984, 25, 5921–5924. (b) Ogoshi, S.;
Kurosawa, H. Chem. Lett. 1990, 1745–1748. (c) Kurosawa,
H.; Ogoshi, S.; Chatani, N.; Kawasaki, Y. Organometallics
6. Ishikura, M.; Terashima, M.; Okamura, K.; Date, T. J. Chem.
Soc., Chem. Commun. 1991, 1219–1221.
7. Ishikura, M.; Matsuzaki, Y.; Agata, I.; Katagiri, N.
Tetrahedron 1998, 54, 13929–13942.
¨
1993, 12, 2869–2871. (d) Granberg, K. L.; Backvall, J. E.
J. Am. Chem. Soc. 1992, 114, 6858–6863.
8. Ishikura, M.; Agata, I.; Katagiri, N. J. Heterocycl. Chem.
1999, 36, 873–879.