Allylic alkylation of indoles with butadiene promoted by palladium catalyst and triethylborane

Article abstract of DOI:10.3987/COM-09-S(S)81

Triethylborane promotes the Pd-catalyzed allylic alkylation of a wide variety of indoles with 1,3-butadiene to provide C3-octadienylindoles and C3-bis(octadienyl)indolenines in good to excellent yields under mild conditions.

Full text of DOI:10.3987/COM-09-S(S)81

HETEROCYCLES, Vol. 80, No. 2, 2010
787
HETEROCYCLES, Vol. 80, No. 2, 2010, pp. 787 - 797. © The Japan Institute of Heterocyclic Chemistry
Received, 28th July, 2009, Accepted, 31st August, 2009, Published online, 2nd September, 2009
DOI: 10.3987/COM-09-S(S)81
ALLYLIC ALKYLATION OF INDOLES WITH BUTADIENE
PROMOTED BY PALLADIUM CATALYST AND TRIETHYLBORANE
a
Masanari Kimura, * Katsumi Tohyama, Yumi Yamaguchi, and
b
b
b
Tomohiko Kohno
a
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University,
b
1-14 Bunkyo, Japan.ꢀꢀ Graduate School of Science and Technology, Nagasaki
University, 1-14 Bunkyo, Japan.
E-mail; masanari@nagasaki-u.ac.jp
Abstract – Triethylborane promotes the Pd-catalyzed allylic alkylation of a wide
variety of indoles with 1,3-butadiene to provide C3-octadienylindoles and
C3-bis(octadienyl)indolenines in good to excellent yields under mild conditions.
Pd-catalyzed allylic alkylation is one of the most attractive strategies for constructing important
1
fundamental constituents of complicated molecules and fine chemicals. Allylation of indoles is a
particularly efficient and successful method for the construction of vital elements found in a diverse range
2
of biologically and physiologically active molecules.
Recently, we have demonstrated that a Pd(0) species in the presence of Et B catalytically activates allylic
3
3
alcohols to undergo electrophilic C-allylation of active methylene compounds and N-allylation of
4
primary and secondary aromatic and aliphatic amines. Furthermore, the Pd/Et B catalytic system
3
worked effectively for the C3 selective allylation of indoles by direct use of allylic alcohols and provided
5
3-allylindoles in excellent yields (Scheme 1). The same procedure was applied to the diastereofacial
selective alkylative cyclic amination on the C2-C3 double bond of tryptophan methyl ester and furnished
hexahydropyrrolo[2,3-b]indole skeletons, found widely in many alkaloids such as physostigmine and
amauromine. We have also found that the combination of Et B and Pd catalyst effectively activates a
3
wide variety of allylic alcohols to undergo either selective monoallylic alkylation of pyrroles at the C2
position with disubstituted allylic alcohols or diallylic alkylation at the C2 and C5 positions with
6
monosubstituted allylic alcohols. It is possible to shift the selectivity in favor of monoallylation under
conditions employing an excess amount of pyrrole and triethylamine as promoters. Moreover, we have
also reported the Pd/Et B system promoted the amphiphilic allylation of aldimines, which are prepared
3
from a wide variety of amines and aldehydes with 2-methylenepropane-1,3-diol to construct nitrogen

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HETEROCYCLES, Vol. 80, No. 2, 2010
7
heterocyclic compounds such as pyrrolidines (Scheme 2). Thus, the combination of Pd(0) catalyst and
Et B works for the generation of both allyl cationic and anionic species directly from allylic alcohols to
3
achieve amphiphilic allylation.
MeNHOCO
Me
O
H
N
H
N
N
N
N
Me
N
H
H
H
Me
O
physostigmine
amauromine
R
R
cat Pd
Et3B
R'
N
H
OH
R'
N
H
CO2Me
NH2
cat Pd
Et3B
CO2Me
NH
OH
N
H
N
H
H
Pd(PPh3)4
Et3B
R
R
R
R
OH
N
H
N
H
N
H
Scheme 1. Pd/Et3B Promoted Allylation of Indole and Pyrrole with Allylic Alcohols
R1
HO
R1
N
R2
cat Pd
N
R2
Et3B
HO
R1
2 nd
1 st
NHR2
OH
electrophilic
allylation
nucleophilic
allylation
Scheme 2. Amphiphilic Allylation of Aldimine
3
Since the development of ꢀ -bis-ꢀ-allylpalladium species from Pd catalysts and conjugated dienes, the
8
transition-metal catalyzed telomerization of conjugated dienes with nucleophiles has become an efficient
9
method of C-C bond and C-hetero atom bond formation. Conjugated dienes are important building

HETEROCYCLES, Vol. 80, No. 2, 2010
789
blocks for cosmetic chemicals and industrial polymers as well as physiologically active molecules such as
10
terpenoids.
Herein we report that the combination of Et B and Pd catalyst promoted the dimerization of butadiene
3
followed by electrophilic allylation at the C3 position of indole to provide 3-(2,7-octadienyl)indole 1, and
the further allylated product, 3,3-bis(2,7-octadienyl)indolenine 2, in good to excellent yields (eq 1).
cat Pd
Et3B
(1)
N
H
R'
N
H
R'
N
R'
2
1
Table 1. Pd-Et3B Catalyzed Allylation of Indole with Butadienea
% isolated yield [ratio]
Et3B
(mmol)
butadiene
(mmol)
time
(hour)
run
1a
2a
1
2
3
4
5
4
4
4
4
6
0
0.3
1.2
2.4
2.4
48
24
24
46
24
0
21
49
65
0
0
trace
12
32
95
a Reaction conditions: indole (1 mmol), Pd(PPh3)4 (5 mol %), butadiene and Et3B
in THF (5 mL) under N2.
The reaction was performed simply by combining a homogeneous mixture of indole, Pd(PPh ) catalyst,
3 4
11
1,3-butadiene, and Et B (30–240 mol %) in dry THF at room temperature under nitrogen atmosphere.
3
Both Pd(PPh ) and Et B are indispensable for the reaction; in the absence of either, no reaction takes
3 4
3
place. The reactions of indole with 4 equivalents of 1,3-butadiene with various amounts of Et B are
3
summarized in Table 1. A catalytic amount of Et B accelerated the dimerization of butadiene and the
3
subsequent electrophilic allylation of indole gave rise to 3-(2,7-octadienyl)indole 1a in moderate yield
(run 2, Table 1). Increasing the amount of Et B generated a higher yield of the further octadienylated
3
product, bis(2,7-octadienyl)indolenine 2a (runs 2-4, Table 1).
In the presence of excess butadiene (6 equivalents) and Et B (2.4 equivalents), indolenine 2a was
3
obtained as the sole product (run 5, Table 1). Next, we examined a wide variety of substituted indoles
under similar catalytic systems. These results are summarized in Table 2. 3-Methylindole (skatole)
was found to be an efficient substrate for the allylic alkylation (run 1, Table 2).

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HETEROCYCLES, Vol. 80, No. 2, 2010
Table 2. Pd-Et3B Promoted Octadienylation of Various Indoles with Butadienea
% isolated yield
time
run
1
indole
(hour)
1
2
2
1b: 83
-
N
H
5
5
1c: 87
1d: 77
1e: 74
1f: 80
1g: 74
2
2c: 10
2d: 23
2e: trace
2f: 13
N
H
NO2
3
N
H
O2N
14
48
48
24
4
N
H
MeO
5b
6b
7
N
H
2g: 17
Br
N
H
no reaction
N
Me
a Reaction conditions: indole (1 mmol), Pd(PPh3)4 (5 mol %), butadiene (4 mmol),
b
and Et3B (2.4 mmol) in THF (5 mL) at room temperature under N2. Reaction
conditions: indole (1 mmol), Pd(OAc)2 (5 mol %), dppf (10 mol %), butadiene (4
mmol), and Et3B (2.4 mmol) in THF (5 mL) at room temperature under N2.
Treatment
of
skatole
with
2.0
equivalents
of
1,3-butadiene
provided
3-methyl-3-(2,7-octadienyl)indolenine 1b in reasonable yield within 2 hours. Thus, the electrophilic
alkylation reaction occurs smoothly with 3-alkyl substituted indoles with their enhanced nucleophilicity
5
on the C3 carbon. 4-Methylindole underwent a similar reaction to give octadienylindole 1c as a major
product along with a trace amount of bis(octadienyl)indolenine 2c (run 2, Table 2). Nitro, methoxy, and
bromo substituted indoles also participated in the reaction and the desired products were obtained in good
to reasonable yields irrespective of the steric and electronic nature of the substituents (runs 3-6, Table 2).

HETEROCYCLES, Vol. 80, No. 2, 2010
791
The indole NH group is required for the reaction to proceed; N-methyl substituted indole did not undergo
the reaction at all under this catalytic system and was recovered quantitatively (run 7, Table 2). These
results imply that Et B coordinates to the nitrogen atom of indole, increasing its acidity, and thus
3
activating the C3 enamine carbon atom towards electrophilic alkylation.
Pd(OAc)2 (5 mol %)
dppf (10 mol %)
NHCO2Me
N
Et3B (2.4 mmol)
THF, rt, 48 h
4 mmol
H
1 mmol
(2)
intramolecular
amination
N
HN
CO2Me
N
H
CO2Me
N
H
3 (97%)
The present reaction was applied to the diastereoselective alkylation of tryptamine derivatives to afford
pyrroloindoles. Under this catalytic system, 1,3-butadiene underwent the dimerization with concomitant
electrophilic allylation at the C3 carbon atom of tryptamine and the subsequent intramolecular amination
toward the electrophilic imine carbon atom furnished the pyrroloindole skeleton (eq 2). Tryptophol also
underwent the consecutive allylic alkylation and amination processes involving dimerization of butadiene
to give 2H-furo[2,3-b]indole in excellent yield (eq 3). This transformation has the potential for the
efficient construction of vital indole alkaloid frameworks.
Pd(OAc)2 (5 mol %)
dppf (10 mol %)
OH
(3)
N
H
4 mmol
Et3B (2.4 mmol)
THF, rt, 48 h
O
N
H
H
4 (98%)
1 mmol
On the basis of these results, a plausible reaction mechanism via dimerization of butadiene promoted by
Pd catalyst and Et B is illustrated in Scheme 3. The Pd(0)-catalyzed dimerization of butadiene affords
3
an ꢀ1,ꢀ3-octadienylpalladium species, which subsequently undergoes protonation at the C6 position to
give the ꢀ3-allylpalladium indolyltriethylborate intermediate. Since indole is a heterocyclic compound
containing a weakly Lewis basic nitrogen, Et B is capable of serving as a Lewis acid to enhance the
3
nucleophilicity of the C3 position by abstraction of a hydrogen atom from the NH bond. The activated
indole readily undergoes Friedel-Crafts alkylation with the ꢀ3-octadienylpalladium species to provide

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HETEROCYCLES, Vol. 80, No. 2, 2010
3-(2,7-octadienyl)indole, along with regeneration of the Pd(0) active species.
L Pd
2 X
Pd
Pd(0)
Pd
L
L
N
NH
BEt3
BEt3
N
Pd
BEt3
L
H
NH
BEt3
Scheme 3. ꢀlausible Reaction Mechanism for Allylation of Indole
In summary, we have shown that a combination of Pd(0) catalyst and Et3B effectively activates butadiene
to undergo the C-allylation of indole via oligomerization of the diene. The C3 carbon atom of the parent
indole moiety serves as a good nucleophile to undergo exhaustive allylations to furnish the C3
bis(octadienyl)indolenine in high yield. Tryptamine and tryptophol also underwent similar allylic
alkylations followed by intramolecular cyclization to afford pyrrolo[2,3-b]indole and
2H-furo[2,3-b]indole frameworks, respectively.
ACKNOWLEDGEMENTS
Financial support from the Ministry of Education, Culture, Sports, Science, and Technology, Japanese
Government (Grant-in-Aid for Scientific Research (B) 21350055) is gratefully acknowledged. This

HETEROCYCLES, Vol. 80, No. 2, 2010
793
work was partially supported by the Asahi Glass Foundation.
REFERENCES AND NOTES
1.
Y. Tamaru, Palladium-Catalyzed Reactions of Allyl and Related Derivatives with
Organoelectrophiles. In Handbook of Organopalladium Chemistry for Organic Synthesis; ed. by
E.-i. Negishi; Wiley-Interscience: New York, 2002, 2, 1917.
2. R. J. Sundberg, ‘Indoles’, Academic Press, London, 1996; J. A. Joule, K. Mills, and G. F. Smith,
‘Heterocyclic Chemistry’ 4th ed., Blackwell Science, Oxford, 2000.
3. M. Kimura, R. Mukai, N. Tanigawa, S. Tanaka, and Y. Tamaru, Tetrahedron, 2003, 59, 7767; Y.
Horino, M. Naito, M. Kimura, S. Tanaka, and Y. Tamaru, Tetrahedron Lett., 2001, 42, 3113; Y.
Tamaru, Y. Horino, M. Araki, S. Tanaka, and M. Kimura, Tetrahedron Lett., 2000, 41, 5705.
4. M. Kimura, M. Futamata, K. Shibata, and Y. Tamaru, Chem. Commun., 2003, 234.
5. M. Kimura, M. Futamata, R. Mukai, and Y. Tamaru, J. Am. Chem. Soc., 2005, 127, 4592.
6. M. Kimura, M. Fukasaka, and Y. Tamaru, Heterocycles, 2006, 67, 535.
7. M. Kimura, T. Tamaki, M. Nakata, K. Tohyama, and Y. Tamaru, Angew. Chem. Int. Ed., 2008, 47,
5803.
8. E. J. Smutny, J. Am. Chem. Soc., 1967, 89, 6793.
9. A. Krotz, F. Vollmüller, G. Stark, and M. Beller, Chem. Commun., 2001, 195.
10. A. Behr, M. Becker, T. Beckmann, L. Johnen, J. Leschinski, and S. Reyer, Angew. Chem. Int. Ed.,
2009, 48, 3598.
11. Typical reaction procedure (run 4, Table 1): Into a N purged flask containing indole (117 mg, 1
2
mmol), Pd(PPh ) (55.6 mg, 0.05 mmol) purged with nitrogen were successively added THF (5 mL),
3 4
1,3-butadiene (400 μL, 4 mmol; liquefied by cooling at -78 ˚C prior to use under argon atmosphere)
and triethylborane (2.4 mL, 1 M hexane; Aldrich) were introduced successively via a syringe. The
reaction mixture was stirred at room temperature for 24 h, during which the reaction was monitored
by means of TLC. After dilution with ethyl acetate (30 mL), the mixture was washed with sat.
NaCl (30 mL). The organic layer was dried (MgSO ) and the solvent was removed in vacuo. The
4
residue was subjected to the column chromatography over silica gel (Fujisirisia NH; eluent:
hexane/EtOAc
=
32:1)
and
3-[(E)-octa-2,7-dienyl]-1H-indole
(1a):
and
3,3-bis[(E)-octa-2,7-dienyl]-3H-indole (2a) were obtained in 65% and 32% yields, respectively.
3-[(E)-Octa-2,7-dienyl]-1H-indole (1a): IR (neat) 3418 (s), 2926 (s), 1639 (s), 968 (s), 741 (s) cm-1;
1H NMR (CDCl3, 400 MHz) ꢀ 1.48 (quint, J = 7.0 Hz, 2 H), 1.98 – 2.07 (m, 4 H), 3.48 (d, J = 7.0 Hz,
2 H), 4.93 (dd, J = 3.4, 10.1 Hz, 1 H), 4.99 (dd, J = 3.4, 17.1 Hz, 1 H), 5.57 (dt, J = 14.2, 7.0 Hz, 1
H), 5.67 (dt, J = 14.2, 7.0 Hz, 1 H), 5.80 (ddt, J = 10.1, 17.1, 7.0 Hz, 1 H), 6.96 (br s, 1 H), 7.09 (t, J

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HETEROCYCLES, Vol. 80, No. 2, 2010
= 7.4 Hz, 1 H), 7.20 (t, J = 7.4 Hz, 1 H), 7.34 (d, J = 7.4 Hz, 1 H), 7.59 (d, J = 7.4 Hz, 1 H), 7.90 (br
13
s, 1 H); C NMR (CDCl3, 100 MHz): ꢀ 28.6, 28.8, 31.2, 110.9, 114.2, 115.5, 119.0, 121.2, 121.8,
127.4, 128.8, 130.8, 136.3, 138.7, 141.9. High-resolution MS, calcd for C16H19N: 225.3288, Found
m/z (relative intensity): 225.1490 (M+ 100), 225 (10), 182 (20).
,
3,3-Di[(E)-octa-2,7-dienyl]-3H-indole (2a): IR (neat) 2926 (s), 1639 (s), 970 (s), 910 (s), 742 (s)
cm-1; 1H NMR (CDCl3, 400 MHz) ꢀ 1.30 (quint, J = 7.0 Hz, 4 H), 1.82 – 1.98 (m, 8 H), 2.39 – 2.54
(m, 4 H), 4.91 (dd, J = 3.4, 10.1 Hz, 2 H), 4.93 (dd, J = 3.4, 17.5 Hz, 2 H), 5.09 (dt, J = 13.9, 7.0 Hz,
2 H), 5.34 (dt, J = 13.9, 7.0 Hz, 2 H), 5.72 (ddt, J = 10.1, 17.5, 7.0 Hz, 2 H), 7.19 – 7.33 (m, 3 H),
13
7.59 (d, J = 7.8 Hz, 1 H), 8.00 (br s, 1 H); C NMR (CDCl3, 100 MHz): ꢀ 28.4, 31.7, 32.9, 37.4,
61.5, 114.3, 121.2, 122.1, 123.9, 125.6, 127.5, 134.3, 138.5, 141.7, 155.5, 177.9. High-resolution
MS, calcd for C24H31N: 333.5096, Found m/z (relative intensity): 333.2451 (M+ 100), 265 (15).
,
Other new compound’s data are as follows.
3-Methyl-3-[(E)-octa-2,7-dienyl]-3H-indole (1b): IR (neat) 2925 (s), 1639 (s), 1603 (s), 972 (s),
910 (s), 743 (s) cm-1; 1H NMR (CDCl3, 400 MHz): ꢀ 1.22 – 1.42 (m, 2 H), 1.34 (s, 3 H), 1.80 – 1.98
(m, 4 H), 2.39 (dd, J = 7.4, 13.7 Hz, 1 H), 2.44 (dd, J = 7.4, 13.7 Hz, 1 H), 4.92 (br d, J = 10.0 Hz, 1
H), 4.60 (br d, J = 17.6 Hz, 1 H), 5.15 (dt, J = 15.1, 7.4 Hz, 1 H), 5.40 (dt, J = 15.1, 7.4 Hz, 1 H),
5.75 (ddt, J = 10.0, 17.6, 7.4 Hz, 1 H), 7.22 – 7.38 (m, 3 H), 7.62 (d, J = 7.8 Hz, 1 H), 8.03 (s, 1 H);
13C NMR (CDCl3, 100 MHz): ꢀ 20.0, 29.0, 32.2, 33.4, 39.6, 57.9, 114.8, 121.5, 122.0, 124.7, 126.3,
128.0, 134.9, 139.0, 143.8, 155.2, 179.4. High-resolution MS, calcd for C17H21N: 239.1674, Found
m/z (relative intensity): 239.1666 (M+ 94), 224 (7), 170 (100).
,
4-Methyl-3-[(E)-octa-2,7-dienyl-1H-indole (1c): IR (neat) 3411 (s), 3321 (s), 2925 (m), 2856 (s),
1
1963 (m), 1618 (m), 1504 (s), 1436 (m), 1342 (m), 1155 (m), 970 (m), 910 (m), 746 (m) cm-1; H
NMR (CDCl3, 400 MHz): ꢀ 1.46 (quint, J = 7.4, 2 H), 2.04 (dtd, J = 7.4, 6.8, 1.2 Hz, 4 H), 2.68 (s, 3
H), 3.62 (dd, J = 6.1, 1.2 Hz, 2 H), 4.93 (dd, J = 10.2, 2.2 Hz, 1 H), 4.98 (dd, J = 17.1, 2.2 Hz, 1 H),
5.46 (dtt, J = 17.1, 6.7, 1.2 Hz, 1 H), 5.73 (dtt, J = 17.1, 6.1, 1.2 Hz, 1 H), 5.80 (ddt, J = 17.1, 10.2,
6.8 Hz, 1 H), 6. 81 (d, J = 7.2 Hz, 1 H), 6.91 (s, 1 H), 7.03 (dd, J = 7.9, 7.4 Hz, 1 H), 7.17 (d, J = 7.9,
13
1 H), 7.89 (br s, 1 H); C NMR (CDCl3, 100 MHz): ꢀ 20.1, 28.8, 30.4, 31.9, 33.3, 108.8, 114.3,
116.3, 120.7, 121.7, 121.9 125.9, 123.0, 130.8, 136.8, 130.9, 136.8, 138.7. High-resolution MS,
calcd for C17H21N: 239.1674, Found m/z (relative intensity): 239.1680 (M+ 100).
,
4-Methyl-3,3-di[(E)-octa-2,7-dienyl]-3H-indole (2c): IR (neat) 3076 (w), 2926 (m), 2854 (w), 1639
(w), 1529 (s), 1441 (w), 1354 (s), 1331 (w), 968 (m), 912 (m), 741 (m) cm-1; 1H NMR (CDCl3, 400
MHz) ꢀ 1.22 (quint, J = 7.3 Hz, 4 H), 1.80 (dt, J = 13.7, 7.3 Hz, 8 H), 2.41 (s, 3 H), 2.60 (dd, J =
13.7, 7.1 Hz, 2 H), 2.72 (dd, J = 13.7, 7.1 Hz, 2 H), 4.84 - 4.91 (m, 6 H), 5.33 (dt, J = 15.1, 7.1 Hz, 2
H), 5.68 (ddt, J = 17.8, 9.5, 6.6 Hz, 2 H), 6.96 (d, J = 7.6 Hz, 1 H), 7.19 (t, J = 7.6 Hz, 1 H), 7.38 (d,

HETEROCYCLES, Vol. 80, No. 2, 2010
795
13
J = 7.6 Hz, 1 H), 7.91 (s, 1 H); C NMR (CDCl3, 100 MHz) ꢀ 18.4, 28.3, 31.5, 32.7, 36.0, 62.9,
114.2, 118.6, 124.0, 127.7, 127.8, 132.8, 133.4, 138.4, 138.6, 156.1, 177.8. HRMS calcd for
C25H33N: 347.2613. Found m/z (relative intensity): 347.2608 (M+, 100).
4-Nitro-3-[(E)-octa-2,7-dienyl]-1H-indole (1d): IR (neat) 3385 (m), 2926 (m), 2853 (w), 1514 (s),
1443 (m), 1325 (s), 1290 (m), 1250 (m), 1111 (m), 972 (m), 912 (m), 787 (m), 732 (s) cm-1; 1H NMR
(CDCl3, 400 MHz) ꢀ 1.42 (quint, J = 7.6 Hz, 2 H), 2.00 (dt, J = 7.6, 6.6 Hz, 4 H), 3.55 (d, J = 6.3 Hz,
2 H), 4.92 (ddt, J = 10.3, 2.2, 1.2 Hz, 1 H), 4.97 (ddt, J = 17.1, 2.2, 1.7 Hz, 1 H), 5.39 (dtt, J = 15.1,
6.6, 1.3 Hz, 1 H), 5.56 (dtt, J = 15.1, 6.3, 1.3 Hz, 1 H), 5.78 (ddt, J = 17.1, 10.3, 6.6 Hz, 1 H), 7.20 (s,
1 H), 7.60 (dd, J = 8.0, 0.9 Hz, 1 H), 7.76 (dd, J = 8.0, 0.9 Hz, 1 H), 8.30 - 8.46 (br s, 1 H); 13C NMR
(CDCl3, 100 MHz) ꢀ 28.7, 30.3, 31.9, 33.2, 114.2, 115.5, 116.5, 117.1, 119.0, 120.6, 126.3, 127.9,
128.9, 131.2, 138.7, 138.9. HRMS calcd for C16H18N2O2: 270.1368. Found m/z (relative intensity):
270.1369 (M+, 100).
4-Nitro-3,3-di[(E)-octa-2,7-dienyl]-3H-indole (2d): IR (neat) 3074 (m), 2926 (s), 2853 (s), 1639 (s),
1593 (w), 1562 (m), 1440 (s), 1416 (m), 964 (s), 910 (s), 789 (s), 748 (s) cm-1; 1H NMR (CDCl3, 400
MHz) ꢀ 1.13 (quint, J = 6.8 Hz, 4 H), 1.71 (dt, J = 7.3, 6.8 Hz, 8 H), 2.77 (dd, J = 13.9, 6.8 Hz, 2 H),
2.98 (dd, J = 13.9, 6.8 Hz, 2 H), 4.77 (dt, J = 14.3, 6.8 Hz, 2 H), 4.89 (dd, J = 16.3, 2.2 Hz, 2 H),
4.86 (dd, J = 10.7, 2.2 Hz, 2 H), 5.30 (dt, J = 14.3, 7.3 Hz, 2 H), 5.63 (ddt, J = 16.3, 10.7, 6.8 Hz, 2
H), 7.48 (dd, J = 8.3, 7.6 Hz, 1 H), 7.86 (d, J = 7.6 Hz, 1 H), 8.00 (d, J = 8.3 Hz, 1 H), 8.08 (s, 1 H);
13C NMR (CDCl3, 100 MHz) ꢀ 28.2, 31.4, 32.6, 35.1, 66.4, 114.3, 121.5, 123.2, 126.7, 128.9, 134.4,
135.6, 138.4, 146.1, 159.2, 180.6. HRMS calcd for C24H30N2O2: 378.2307. Found m/z (relative
intensity): 378.2297 (M+, 100).
5-Nitro-3-[(E)-octa-2,7-dienyl]-1H-indole (1e): IR (neat) 3375 (s), 2926 (m), 2839 (w), 1624 (w),
1510 (m), 1470 (m), 1319 (s), 1221 (m), 1101 (m), 968 (w), 912 (w), 738 (w) cm-1; 1H NMR (CDCl3,
400 MHz) ꢀ 1.49 (quint, J = 7.4 Hz, 2 H), 2.03 - 2.09 (m, 4 H), 3.49 (dd, J = 5.1, 0.7 Hz, 2 H), 4.93
(ddt, J = 10.3, 2.2, 1.2 Hz, 1 H), 4.99 (d, J = 17.1, 2.2, 1.7 Hz, 1 H), 5.56 - 5.69 (m, 2 H), 5.80 (ddt, J
= 17.1, 10.3, 6.8 Hz, 1 H), 7.11 (s, 1 H), 7.36 (d, J = 9.0 Hz, 1 H), 8.10 (dd, J = 9.0, 2.2 Hz, 1 H),
13
8.27 - 8.38 (br s, 1 H), 8.57 (d, J = 2.2 Hz, 1 H); C NMR (CDCl3, 100 MHz) ꢀ 28.3, 28.7, 28.3,
31.8, 33.2, 110.8, 114.4, 116.5, 117.6, 117.7, 118.2, 126.8, 127.7, 131.8, 138.6, 139.3, 141.4. HRMS
calcd for C16H18N2O2: 270.1368. Found m/z (relative intensity): 270.1369 (M+, 100), 269 (7).
5-Methoxy-3-[(E)-octa-2,7-dienyl]-1H-indole (1f): IR (neat) 3417 (s), 2927 (s), 2831(m), 1624(s),
1585(m), 1485 (m), 1454 (s), 1215 (m), 1172 (m), 968 (m), 914 (m), 831 (m) cm-1; 1H NMR (CDCl3,
400 MHz): ꢀ 1.49 (quint, J = 7.3, 2 H), 2.05 (dt, J = 6.6, 7.3 Hz, 4 H), 3.41 (d, J = 6.1 Hz, 2 H), 3.84
(s, 3 H), 4.92 (dd, J = 10.2, 2.0 Hz, 1 H), 4.98 (dd, J = 17.1, 2.0 Hz, 1 H), 5.58 (dd, J = 15.2, 6.6 Hz,
1 H), 5.66 (dd, J = 15.3, 6.1 Hz, 1 H), 5.79 (ddt, J = 17.1, 10.2, 6.6 Hz, 1 H), 6.83 (dd, J = 8.8, 2.4

796
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Hz, 1 H), 6.93 (s, 3 H), 7.03 (d, J = 2.4 Hz, 1 H), 7.22 (d, J = 8.8 Hz, 1 H), 7.88 (br s, 1 H); C
NMR (CDCl3, 100 MHz): ꢀ 28.7, 28.8, 31.9, 33.2, 55.9, 111.6, 112.0, 114.3, 115.1, 122.1, 127.8,
128.7, 130.8 131.5, 138.7, 153.7. High-resolution MS, calcd for C17H21NO: 255.1623, Found m/z
(relative intensity): 255.1620 (M+ 100).
,
5-Methoxy-3-bis[(E)-octa-2,7-dienyl]-3H-indole (2f): IR (neat) 3074 (s), 2925 (s), 2837(m),
1963(s), 1591(m), 1554 (m), 1469 (s), 1336 (m), 1228 (m), 1176 (m), 966 (m), 910 (m), 810 (m)
cm-1; 1H NMR (CDCl3, 400 MHz) ꢀ 1.31 (quint, J = 7.3 Hz, 4 H), 1.89 - 1.93 (m, 8 H), 2.39 (dd, J =
13.4, 6.8 Hz, 2 H), 2.46 (dd, J = 13.3, 7.4 Hz, 2 H), 3.82 (s, 3 H), 4.90 (dd, J = 10.2, 3.2 Hz, 1 H),
4.91 (dd, J = 10.2, 3.2 Hz, 1 H), 4.92 (dd, J = 17.1, 3.2 Hz, 1 H), 4.93 (dd, J = 17.1, 3.2 Hz, 1 H),
5.10 (dd, J = 15.1, 6.8 Hz, 2 H), 5.37 (dt, J = 15.1, 7.4 Hz, 2 H), 5.72 (ddt, J = 17.1, 10.2, 6.6 Hz, 2
H), 6. 80 - 6.84 (m, 2 H), 7.74 - 7.50 (m, 1 H), 7.88 (br s, 1 H); 13C NMR (CDCl3, 100 MHz): ꢀ 28.5,
31.7, 32.9, 37.5, 55.7, 62.6, 109.0, 112.1, 114.3, 121.1, 124.0, 134.3, 138.5 143.5, 149.3, 158.2,
175.9. High-resolution MS, calcd for C25H33NO: 363.2562, Found m/z (relative intensity): 363.2568
(M+ 66), 309 (100).
,
6-Bromo-3-[(E)-octa-2,7-dienyl]-1H-indole (1g): IR (neat): 3425 (s), 2925 (s), 2854 (m), 1640 (m),
1614 (m), 1454 (m), 1332 (m), 1089 (m), 968 (m), 802 (m) cm-1; 1H NMR (CDCl3, 400 MHz) ꢀ 1.46
(quint, J = 7.4 Hz, 2 H), 2.04 (dt, J = 7.4, 6.3 Hz, 1 H), 2.04 (dt, J = 7.4, 6.7, 1.8 Hz, 1 H), 3.42 (dd,
J = 6.1, 1.1Hz, 1 H), 4.93 (dd, J = 10.1, 1.8 Hz, 1 H), 4.98 (dq, J = 17.1, 1.8 Hz, 1 H), 5.59 (dt, J =
16.3, 6.3 Hz, 1 H), 5.63 (dt, J = 16.3, 6.1 Hz, 1 H), 5.79 (ddt, J = 17.1, 10.1, 6.7 Hz, 1 H), 6.93 (t, J
= 1.1 Hz, 1 H), 7.18 (dd, J = 8.4, 1.7 Hz, 1 H), 7.44 (d, J = 8.4 Hz, 1 H), 7.49 (d, J = 1.7 Hz, 1 H),
13
7.90 (br s, 1 H); C NMR (CDCl3, 100 MHz) ꢀ 28.5, 28.7, 31.8, 33.2, 113.8, 114.3, 115.4, 115.7,
120.3, 121.9, 122.4, 126.3, 128.4, 131.1, 138.6. High-resolution MS, calcd for C16H18BrN: 303.0623,
Found m/z (relative intensity): 303.0629 (M+ 49), 249 (100).
,
6-Bromo-3,3-bis[(E)-octa-2,7-dienyl]-3H-indole (2g): IR (neat) 3074 (m), 2925 (s), 2825 (m), 1639
(s), 1593 (s), 1471 (s), 970 (s), 910 (s), 802 (m) cm-1; 1H NMR (CDCl3, 400 MHz) ꢀ 1.31 (quint, J =
7.5 Hz, 4 H), 1.82 - 1.95 (m, 8 H), 2.41 (dd, J = 13.9, 7.8 Hz, 2 H), 2.47 (dd, J = 13.9, 7.8 Hz, 2 H),
4.92 (dd, J = 10.4, 1.6 Hz, 2 H), 4.94 (dq, J = 17.0, 1.6 Hz, 2 H), 5.03 (dt, J = 14.9, 7.8 Hz, 2 H),
5.36 (dt, J = 14.9, 6.9 Hz, 2 H), 5.73 (ddt, J = 17.0, 10.2, 6.7 Hz, 2 H), 7.12 (dd, J = 8.0 Hz, 1 H),
7.36 (dd, J = 8.0, 1.8 Hz, 1 H), 7.73 (d, J = 1.8 Hz, 1 H); 13C NMR (CDCl3, 100 MHz) ꢀ 28.4 (2C),
32.9 (4C), 37.2 (2C), 61.7, 114.4 (2C), 120.9, 123.3, 123.5 (4C), 124.4, 128.5, 134.7 138.4 (2C),
140.6, 157.0. High-resolution MS, calcd for C24H30BrN: 411.1562, Found m/z (relative intensity):
411.1556 (M+ 100).
,
1,2,3,3a,8,8a-Hexahydro-1-methoxycarbonyl-3a-(2,7-octadienyl)-pyrrolo[2,3-b]indole (3): IR
(neat) 2925 (s), 2856 (s), 1705 (s), 1639 (s), 1606 (s), 1490 (s), 1448 (s), 1386 (s), 1211 (s), 968 (s),

HETEROCYCLES, Vol. 80, No. 2, 2010
797
740 (s); 1H NMR (CDCl3, 400 MHz) ꢀ 1.43 (quint, J = 7.4 Hz, 2 H), 2.01 - 2.14 (m, 4 H), 2.37 (d, J
= 6.3 Hz, 2 H), 3.03 (d, J = 3.2 Hz, 1 H), 3.57 (dt, J = 2.7, 7.3 Hz, 1 H), 3.58 (dd, J = 2.7, 10.0 Hz, 1
H), 3.64 (s, 3 H), 4.97 (dd, J = 2.0, 17.1 Hz, 1 H), 4.93 (dd, J = 1.9, 10.2 Hz, 1 H), 5.12 (s, 1 H), 5.44
(dt, J = 6.3, 14.9 Hz, 2 H), 5.77 (ddt, J = 6.7, 10.2, 17.1 Hz, 1 H), 6.53 - 6.58 (m, 2 H), 6.75 - 6.70
(m, 2 H), 7.00 - 7.05 (m, 2 H); 13C NMR (CDCl3, 100 MHz) ꢀ 28.6, 31.9, 33.1, 34.9, 41.0, 45.8, 52.4,
57.3, 80.1, 109.1, 114.3, 118.5, 123.0, 125.0, 128.1, 131.8, 134.1, 138.5, 155.4. Anal. Calcd for
C20H26N2O2: C, 73.59; H, 8.03; N, 8.58; O, 9.80. Found: C, 73.42; H, 8.40; N, 8.38.
3,3a,8,8a-Tetrahydro-3a-(2,7-octadienyl)-2H-furo[2,3-b]indole (4): IR (neat) 3352 (s), 2858 (s),
1639 (s), 1611 (s), 910 (s), 742 (s) cm-1;1H NMR (CDCl3, 400 MHz) ꢀ 1.40 (quint, J = 7.4 Hz, 2 H),
1.90 – 2.02 (m, 6 H), 2.41 (dd, J = 7.8, 14.1 Hz, 1 H), 2.51 (dd, J = 6.3, 14.1 Hz, 1 H), 3.54 (m, 1 H),
3.94 (m, 1 H), 4.54 (br s, 1 H), 4.93 (br d, J = 10.3 Hz, 1 H), 4.96 (br d, J = 14.3 Hz, 1 H), 5.33 (m, 1
H), 5.35 (br s, 1 H), 5.46 (m, 1 H), 5.76 (dddd, J = 6.3, 7.8, 10.3, 14.3 Hz, 1 H), 6.57 (d, J = 7.6 Hz,
1 H), 6.74 (t, J = 7.6 Hz, 1 H), 7.03 – 7.07 (m, 2 H);13C NMR (CDCl3, 100 MHz) ꢀ 28.6, 31.9, 33.0,
39.5, 41.2, 57.9, 67.1, 97.4, 108.1, 114.3, 118.6, 123.5, 125.6, 127.9, 132.4, 133.8, 138.6, 149.4.
High-resolution MS, calcd for C18H23NO: 269.1780, Found m/z (relative intensity): 269.1780 (M+
,
100), 215 (11).