Highly efficient InBr3 catalyzed michael addition of indoles to α,β-Unsaturated Esters

Article abstract of DOI:10.1002/cjoc.201190011

A highly efficient synthetic strategy toward Michael addition of indoles to α,β-unsaturated esters has been developed using Lewis acid InBr ₃ as catalyst. The reactions generated 3-substituted indoles in high yields with excellent regio-selecti

Full text of DOI:10.1002/cjoc.201190011

FULL PAPER
Highly Efficient InBr3 Catalyzed Michael Addition of Indoles to
α,β-Unsaturated Esters
Liu, Pinga(刘平)
Chen, Weia(陈巍)
Ren, Kaia(任凯)
Wang, Lei*,a,b(王磊)
a Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
A highly efficient synthetic strategy toward Michael addition of indoles to α,β-unsaturated esters has been de-
veloped using Lewis acid InBr3 as catalyst. The reactions generated 3-substituted indoles in high yields with excel-
lent regio-selectivity in the presence of catalytic amount of InBr3 under mild reaction conditions. The method is
simple, efficient and practical.
Keywords Michael addition, indole, α,β-unsaturated ester, Lewis acid, InBr3
Introduction
InCl3-catalysed conjugate addition of indoles with elec-
tron-deficient olefins, but, olefin substrate was limited
to α,β-unsaturated ketones.
Various indole derivatives occur in many pharma-
cologically and biologically active compounds.1 Among
them, 3-substituted indoles are important building
blocks for the synthesis of biologically active com-
pounds and natural products.2 The Michael addition of
indoles to electron-deficient olefins is one of the general
and concise routes to 3-substituted indoles. Typically,
these conjugate addition reactions are performed under
the influence of strong bases, such as alkali metal
alkoxides or hydroxides.3 The strong basic reaction
conditions often lead to a number of undesirable side
reactions, such as aldol cyclizations, ester solvolysis,
and base induced rearrangements such as retro-Claisen
or retro-Michael reactions and polymerization reactions.
As results, numerous methods have been reported for
the conjugate addition of indoles to electron-deficient
olefins through the activation of the Michael acceptor in
the presence of Lewis acids,4,5 because Lewis acids
have been found to catalyze conjugate addition reac-
tions effectively under mild reaction conditions avoid-
ing undesirable side reaction products along with the
3-substituted indoles.6,7
In continuation of our efforts in developing selective,
efficient, mild and environmental friendly synthetic
methodologies for the preparation of heterocycle de-
rivatives,14 herein, we wish to report an InBr3-catalyzed
Michael addition of indoles to various α,β-unsaturated
ketones, as well as less active α,β-unsaturated esters
procedure for the direct synthesis of 3-substituted in-
doles under efficient, simple and practical reaction con-
ditions (Scheme 1). In addition, the notable advantages
of this methodology are mild condition, short reaction
times, high yields and free from any side reaction prod-
ucts.
Scheme 1
The utility of indium(III) salts as Lewis acids in or-
ganic synthesis has received a great deal of interest due
to their relatively low toxicity, stability in air and water,
recyclability, operational simplicity, strong tolerance to
oxygen and nitrogen-containing substrates and func-
tional groups.8 Their potential as Lewis acid catalysts
for fundamental reactions, such as the Diels-Alder,9
Friedel-Crafts,10 Mukaiyama aldol,11 and Sakurai-
Hosomi allylation reactions,12 has been extensively in-
vestigated. Most recently, Yadav et al.13 reported an
Results and discussion
In our preliminarily investigation on the model reac-
tion of N-methyl indole with ethyl acrylate, it was found
that the reaction could be finished under very simple
reaction conditions in the presence of catalytic amount
of InBr3 (10 mol%) in the absence of any additive,
*
E-mail: leiwang@chnu.edu.cn; Tel.: 0086-0561-3802069; Fax: 0086-0561-3090518
Received March 5, 2010; revised July 13, 2010; accepted August 11, 2010.
Project supported by the National Natural Science Foundation of China (No. 20972057).
Chin. J. Chem. 2010, 28, 2399— 2403
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Liu et al.
FULL PAPER
which gives the desired ethyl 3-(1-methyl-1H-indol-3-
yl)propanoate in 91% yield (Table 1, Entry 1). The ef-
fect of solvent, catalyst, reaction temperature and time
on the reaction was investigated and the results are
summarized in Table 1. As can be seen from Table 1,
the solvents play an important role in the reaction. It
was found that ClCH2CH2Cl is the best solvent among
the solvents tested, and the reaction underwent smoothly
in ClCH2CH2Cl and generated the desired product in
91% yield, while DMF or CH3CN afforded trace
amount of the desired product. Moreover, use of diox-
ane, CH3NO2, toluene, C2H5OH and DMSO as solvents
led to slower reactions (Table 1, Entries 1—8). Among
a variety of catalyst species examined, InBr3 was found
to be the most effective one. When using InCl3,
In(OAc)3, and In(OTf)3 instead of InBr3 as catalyst, their
efficiencies were lower than that of InBr3 for the model
reaction (Table 1, Entries 1, and 9—11). It is important
to note that no Michael addition product was isolated
using In(OAc)3 as catalyst. This clearly demonstrates
the great effect of a conjugate anion on the activity of
Lewis acid. Most of the reported conjugate additions of
heterocyclic enamines, especially indoles have been
restricted to highly reactive Michael acceptor, such as
α,β-unsaturated ketones or nitroolefins. We were
pleased to find that InBr3 efficiently catalyzed the con-
jugate addition of indoles to weaker acceptor
α,β-unsaturated esters (Table 1, Entries 1 and 9—11).
With respect to the catalyst loading, when less than 10
mol% of InBr3 was used, the reaction did not go to
completion, but that a higher loading (more than 10
mol%) of the catalyst gave a satisfactory results (Table
1, Entries 12 and 13).
During the course of our further optimization of the
reaction conditions, the reactions were generally com-
plete in a matter of hours, but the time, as expected, was
inversely proportional to the temperature. A reaction
temperature of 80 ℃ for 12 h was found to be optimal
(Table 1, Entries 14—16). Thus, the optimized reaction
conditions for the reaction were found to be InBr3 (10
mol%) in ClCH2CH2Cl at 80 ℃ for 12 h.
To investigate the generality of this method, the re-
action of various indoles and different α,β-unsaturated
esters was examined under the optimized reaction con-
ditions (10 mol% of InBr3, in ClCH2CH2Cl at 80 ℃ for
12 h). All of the results are summarized in Table 2. As
shown in Table 2, in general, the reactions proceeded
smoothly with high selectivities for various indoles with
α,β-unsaturated esters in good to excellent isolated
yields (up to 96%, Table 2, Entries 1—11). The process
worked noticeably more efficiently for N-substituted
indole, such as N-methyl indole, N-ethyl indole, with
different α,β-unsaturated esters and the yields of addi-
tion products were excellent (Table 2, Entries 1—3,
7—11 vs. 4—6). In addition, we found that the electron
and steric effect of α,β-unsaturated esters's substituents
(alcohol part) had little impact on the yields of the reac-
Table 1 Optimization of the reaction conditionsa
Entry
1
Catalyst (mol%)
Solvent/Temp. (℃)
Yieldb/%
91
InBr3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (10)
InCl3 (10)
In(OAc)3 (10)
In(OTf)3 (10)
InBr3 (5)
ClCH2CH2Cl/80
DMSO/110
2
24
3
Toluene/110
59
4
CH3CN/80
Trace
Trace
73
5
DMF/110
6
Dioxane/100
7
CH3NO2/100
C2H5OH/78
66
8
44
9
ClCH2CH2Cl/80
ClCH2CH2Cl/80
ClCH2CH2Cl/80
ClCH2CH2Cl/80
ClCH2CH2Cl/80
ClCH2CH2Cl/60
ClCH2CH2Cl/60
ClCH2CH2Cl/60
56
10
11
12
13
14
15c
16d
NR
44
61
InBr3 (15)
InBr3 (10)
InBr3 (10)
InBr3 (10)
91
55
73
90
a
Reaction conditions: N-methyl indole (0.50 mmol), ethyl acrylate (0.50 mmol), In salt (10 mol%), stirred in solvent (1.5 mL) at the
temperature indicated in Table 1 for 12 h. b Isolated yield. c Reaction was conducted for 24 h. d Reaction was conducted for 48 h. NR＝no
reaction.
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Chin. J. Chem. 2010, 28, 2399— 2403

Highly Efficient InBr3 Catalyzed Michael Addition of Indoles to α,β-Unsaturated Esters
Table 2
InBr3-catalyzed Michael addition of indoles to
Continued
α,β-Unsaturated compound Yieldb/%
α,β-unsaturated compoundsa
Entry
13c
Indole
93
94
14c
Entry
1
Indole
α,β-Unsaturated compound Yieldb/%
a
Reaction conditions: indole (1.0 mmol), α,β-unsaturated com-
pound (1.0 mmol), InBr3 (35.5 mg, 0.1 mmol) was stirred at 80
℃ for 12 h. b Isolated yield. c Reactions were carried out at room
temperature for 4 h.
93
tion. It is important to note that N-ethyl 2-phenyl indole
also reacted with α,β-unsaturated esters to generate the
corresponding product in excellent yields (Table 2, En-
tries 11 and 12). For the same indoles, α,β-unsaturated
ketones and aldehydes, such as (E)-1-phenylbut-2-en-1-
one, (E)-pent-3-en-2-one, and acrylaldehyde exhibit
more reactivity than α,β-unsaturated esters. The reac-
tions of indoles with α,β-unsaturated ketones and alde-
hydes underwent smoothly at room temperature (Table
2, Entries 12—14).
2
90
96
78
76
86
90
93
92
90
91
92
3
4
Overall, almost all reactions were clean and gave the
C3-substitution product exclusively, and the target
compounds were obtained in good to excellent yields
with no formation of side products such as dimers or
polymers, which are frequently encountered under the
influence of strong protic acids.
5
6
Conclusion
In conclusion, InBr3 has been demonstrated to be a
highly selective and efficient catalyst for the Michael
addition of indoles to a variety of α,β-unsaturated esters.
The reactions were performed smoothly to generate the
desired products 3-substituted indoles in good yields
under safe experimental conditions. The notable advan-
tages of this methodology are mild condition, short re-
action time, high yields and free from any side reaction
products. This method offers one of the important mo-
tifs for synthesis of 3-substituted indoles, as natural
products, biologically active compounds and pharma-
ceutical agents.
7
8
9
10
11
12c
Experimental
Physical measurements and materials
All 1H NMR and 13C NMR spectra were recorded on
a 400 MHz Bruker FT-NMR spectrometers. All chemi-
cal shifts are given as δ value with reference to tetrame-
thylsilane (TMS) as an internal standard. Products were
purified by flash chromatography on 230—400 mesh
silica gel, SiO2.
The chemicals and solvents were purchased from
commercial suppliers either from Aldrich, Fluka, USA
Chin. J. Chem. 2010, 28, 2399— 2403
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Liu et al.
FULL PAPER
137.0, 126.5, 124.9, 121.5, 119.3, 119.1, 118.5, 109.2,
50.5, 32.5, 32.4, 30.2, 26.8, 21.3.
or Shanghai Chemical Company, China and were used
without purification prior to use.
Butyl 3-(1-methyl-1H-indol-3-yl)propanoate 1H
NMR (CDCl3, 400 MHz) δ: 7.26—7.18 (m, 2H),
7.11—7.07 (m, 1H), 4.08—4.05 (m, 2H), 3.68 (s, 3H),
3.09—3.06 (m, 2H), 2.71—2.66 (m, 2H), 1.60—1.53
(m, 2H), 1.37—1.28 (m, 2H), 0.90 (t, J＝7.3 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ: 173.4, 136.9, 127.5,
126.2, 121.5, 118.7, 118.6, 113.4, 109.1, 64.2, 35.1,
32.4, 30.6, 20.5, 19.0, 13.6. Anal. calcd for C16H21NO2:
C 74.10, H 8.16, N 5.40; found C 74.39, H 8.01, N 5.57.
General procedure for the synthesis of 3-substituted
indoles through the Michael addition of indoles to
α,β-unsaturated esters
To a solution of indole 1 (1.0 mmol) and
α,β-unsaturated ester 2 (1.0 mmol) in ClCH2CH2Cl (3.0
mL) was added InBr3 (0.1 mmol) in one portion. The
reaction mixture was heated to 80 ℃ for 12 h with
stirring under a nitrogen atmosphere. After cooling, the
reaction mixture was extracted with ethyl acetate and
the organic layer was dried over Na2SO4. Then, the or-
ganic solution was concentrated with a rotary evapora-
tor, and the residue was purified by column chromatog-
raphy on silica gel to afford the desired product.
Ethyl 3-(1-methyl-1H-indol-3-yl)propanoate15 1H
NMR (CDCl3, 400 MHz) δ: 7.57 (d, J＝8.0 Hz, 1H),
7.24—7.15 (m, 1H), 7.10—7.06 (m, 1H), 6.80 (s, 1H),
4.11 (dd, J＝7.1, 7.3 Hz, 2H), 3.65 (s, 3H), 3.07 (t, J＝
7.5 Hz, 2H), 2.66 (t, J＝7.3 Hz, 2H), 1.21 (t, J＝7.0 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ: 173.2, 136.9,
127.5, 126.2, 121.4, 118.7, 118.6, 113.3, 109.0, 60.2,
35.1, 32.4, 20.4, 14.1.
Butyl 3-(1H-indol-3-yl)propanoate
1H NMR
(CDCl3, 400 MHz) δ: 8.02 (br, s, 1H), 7.59 (d, J＝7.7
Hz, 1H), 7.32—7.29 (m, 1H), 7.21—7.15 (m, 1H),
7.12—7.08 (m, 1H), 6.95—6.94 (m, 1H), 4.04 (t, J＝6.7
Hz, 2H), 3.11—3.07 (m, 2H), 2.71 (t, J＝7.4 Hz, 2H),
1.61—1.54 (m, 2H), 1.37—1.28 (m, 2H), 0.90 (t, J＝7.3
Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ: 173.5, 136.2,
127.1, 121.9, 121.4, 119.2, 118.6, 114.9, 111.1, 64.3,
35.0, 30.6, 20.6, 19.0, 13.6. Anal. calcd for C15H19NO2:
C 73.44, H 7.81, N 5.71; found C 73.29, H 8.05, N 5.87.
Octan-2-yl 3-(1-methyl-1H-indol-3-yl)propanoate
1H NMR (CDCl3, 400 MHz) δ: 7.59—7.57 (m, 1H),
7.28—7.26 (m, 1H), 7.23—7.21 (m, 1H), 7.12—7.10
(m, 1H), 6.85 (s, 1H), 3.99 (dd, J＝2.2, 3.7 Hz, 2H),
3.71 (s, 3H), 3.09 (t, J＝7.7 Hz, 2H), 2.70 (t, J＝7.3 Hz,
2H), 1.56—1.50 (m, 1H), 1.34—1.29 (m, 2H), 1.27—
1.25 (m, 6H), 0.89—0.87 (m, 3H), 0.86—0.84 (m, 3H);
13C NMR (CDCl3, 100 MHz) δ: 173.6, 137.0, 127.5,
126.2, 126.1, 121.5, 118.7, 118.6, 113.4, 109.1, 66.8,
38.7, 35.2, 32.5, 30.3, 28.9, 23.7, 22.9, 20.6, 14.0, 10.9.
Anal. calcd for C20H29NO2: C 76.15, H 9.27, N 4.44;
found C 76.02, H 9.41, N 4.67.
Methyl 3-(1-methyl-1H-indol-3-yl)propanoate16
1H NMR (CDCl3, 400 MHz) δ: 7.56 (d, J＝7.6 Hz, 1H),
7.25—7.16 (m, 2H), 7.11—7.07 (m, 1H), 6.81 (s, 3H),
3.66 (s, 3H), 3.64 (s, 3H), 3.07 (t, J＝7.1 Hz, 2H), 2.68
(t, J＝7.7 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ:
173.7, 136.9, 127.4, 126.2, 121.5, 118.6, 113.3, 109.1,
51.4, 34.9, 32.4, 20.4.
Methyl 3-(1H-indol-3-yl)propanoate17 1H NMR
(CDCl3, 400 MHz) δ: 7.99 (s, 1H), 7.61—7.57 (m, 1H),
7.34—7.29 (m, 1H), 7.19 (t, J＝7.3 Hz, 1H), 6.98 (s,
1H), 3.67 (s, 3H), 3.10 (t, J＝7.3 Hz, 2H), 2.72 (t, J＝
7.7 Hz, 2H); 13C NMR (CDCl3, 400 MHz) δ: 173.8,
136.2, 127.1, 122.0, 121.4, 119.3, 118.6, 111.1, 51.1,
34.7, 20.6.
2-Phenoxyethyl
3-(1-methyl-1H-indol-3-yl)pro-
panoate 1H NMR (CDCl3, 400 MHz) δ: 7.58—7.56
(m, 1H), 7.30—7.18 (m, 4H), 7.12—7.07 (m, 1H),
6.89—6.85 (m, 2H), 6.82 (s, 1H), 4.42—4.40 (m, 2H),
4.10—4.07 (m, 2H), 3.63 (s, 3H), 3.09 (t, J＝7.7 Hz,
2H), 2.74 (t, J＝7.4 Hz, 2H); 13C NMR (CDCl3, 100
MHz) δ: 173.2, 158.3, 136.8, 129.4, 127.4, 126.3, 121.5,
121.0, 118.7, 118.6, 114.5, 113.1, 109.1, 65.7, 62.7,
34.9, 32.4, 26.8, 20.4. Anal. calcd for C20H21NO3: C
74.28, H 6.55, N 4.33; found C 74.49, H 6.41, N 4.52.
2,2,2-Trifluoroethyl 3-(1-methyl-1H-indol-3-yl)-
propanoate 1H NMR (CDCl3, 400 MHz) δ: 7.58 (d,
J＝8.1 Hz, 1H), 7.30—7.21 (m, 2H), 7.13—7.10 (m,
1H), 6.86 (s, 1H), 4.45 (dd, J＝8.5, 8.5 Hz, 2H), 3.73 (s,
3H), 3.12 (t, J＝7.5 Hz, 2H), 2.81 (t, J＝7.4 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ: 171.7, 136.9, 127.3,
126.4, 121.6, 118.8, 118.6, 112.6, 109.2, 60.4, 60.0,
34.5, 32.6, 20.2. Anal. calcd for C14H14F3NO2: C 58.95,
H 4.95, N 4.91; found C 58.79, H 5.11, N 5.07.
Ethyl 3-(1H-indol-3-yl)propanoate18 1H NMR
(CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.62—7.59 (m, 1H),
7.34—7.31 (m, 1H), 7.21—7.16 (m, 1H), 7.14—7.10
(m, 1H), 6.98—6.97 (m, 1H), 4.13 (dd, J＝7.0, 7.4 Hz,
2H), 3.12—3.08 (m, 2H), 1.73—1.69 (m, 2H), 1.23 (t,
J＝7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ: 173.5,
136.2, 127.1, 122.0, 121.4, 119.2, 118.7, 114.9, 111.1,
60.3, 34.9, 20.6, 14.2.
1-Phenyl-3-(1-methyl-1H-indol-3-yl)-butan-1-
one19 1H NMR (CDCl3, 400 MHz) δ: 7.43—7.41 (br,
s, 1H), 7.30 (t, J＝8.1 Hz, 2H), 7.24 (dd, J＝7.3, 7.5 Hz,
3H), 7.16 (dd, J＝6.7, 6.5 Hz, 2H), 7.01 (t, J＝7.3 Hz,
1H), 6.82 (s, 1H), 4.82 (t, J＝7.6 Hz, 1H), 3.70 (s, 3H),
3.26—3.11 (m, 2H), 2.06 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ: 207.6, 144.1, 137.2, 128.4, 127.6, 126.8,
126.3, 126.1, 121.7, 119.4, 118.8, 117.2, 109.2, 50.4,
38.3, 32.7, 30.3, 26.9.
2,2,2-Trifluoroethyl 3-(1-ethyl-2-phenyl-1H-indol-
3-yl)propanoate 1H NMR (CDCl3, 400 MHz) δ:
7.63—7.61 (m, 1H), 7.65—7.62 (m, 1H), 7.51—7.44
(m, 3H), 7.40—7.36 (m, 3H), 7.28—7.23 (m, 1H),
7.18—7.14 (m, 1H), 4.35 (dd, J＝3.1, 8.4 Hz, 2H),
4.05—3.99 (m, 2H), 3.08—3.02 (m, 2H), 2.68—2.62
(m, 2H), 1.23—1.18 (m, 3H); 13C NMR (CDCl3, 100
MHz) δ: 171.5, 137.7, 135.7, 131.9, 130.4, 128.5, 128.3,
127.3, 124.3, 121.7, 119.3, 118.7, 110.9, 109.7, 60.3,
4-(1-Methyl-1H-indol-3-yl)pentan-2-one20 1H NMR
(CDCl3, 400 MHz) δ: 7.63—7.61 (m, 1H), 7.26—7.18
(m, 2H), 7.11—7.07 (m, 1H), 6.79 (s, 1H), 3.68 (s, 3H),
3.63—3.56 (m, 1H), 2.89 (dd, J＝5.9, 10.2 Hz, 1H),
2.67 (dd, J＝8.4, 7.8 Hz, 1H), 2.06 (s, 3H), 1.36 (d, J＝
6.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ: 208.5,
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Chin. J. Chem. 2010, 28, 2399— 2403

Highly Efficient InBr3 Catalyzed Michael Addition of Indoles to α,β-Unsaturated Esters
59.9, 38.5, 34.8, 19.9, 15.3. Anal. calcd for C21H20F3-
NO2: C 67.19, H 5.37, N 3.73; found C 67.35, H 5.29, N
3.57.
(e) Bandini, M.; Melchiorre, P.; Melloni, A.; Umani-Ronchi,
A. Synthesis 2002, 1110.
(a) Soriente, A.; Spinella, A.; De Rosa, M.; Giordano, M.;
Scettri, A. Tetrahedron Lett. 1997, 38, 289.
(b) Kotsuki, H.; Arimura, K.; Ohishi, T.; Maruzasa, R. J.
Org. Chem. 1999, 64, 3770.
(c) Bartoli, G.; Bosco, M.; Bellucci, M. C.; Marcantoni, E.;
Sambri, L.; Torregiani, E. Eur. J. Org. Chem. 1999, 617.
(a) Kobayashi, S. Synlett 1994, 689.
(b) Kobayashi, S.; Hachiya, I.; Takahori, T.; Araki, M.;
Ishitani, H. Tetrahedron Lett. 1992, 33, 6815.
(c) Mori, Y.; Kakumoto, K.; Manabe, K.; Kobayashi, S.
Tetrahedron Lett. 2000, 41, 3107.
(a) Frost, C. G.; Chauhan, K. K. J. Chem. Soc., Perkin
Trans. 1 2000, 3015.
(b) Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro, L. Curr.
Org. Chem. 2003, 7, 1661.
(c) Frost, C. G.; Hartley, J. P. Mini-Rev. Org. Chem. 2004, 1,
1.
(d) Zhang, Z.-H. Synlett 2005, 711.
6
Ethyl 3-(1-ethyl-2-phenyl-1H-indol-3-yl)propano-
ate 1H NMR (CDCl3, 400 MHz) δ: 7.65 (d, J＝8.1 Hz,
1H), 7.49—7.42 (m, 3H), 7.38—7.34 (m, 3H), 7.23 (t,
J＝7.0 Hz, 1H), 7.24 (t, J＝7.0 Hz, 1H), 4.07—3.98 (m,
4H), 3.01 (t, J＝8.1 Hz, 2H), 2.55 (t, J＝8.2 Hz, 2H),
1.20—1.15 (m, 6H); 13C NMR (CDCl3, 100 MHz) δ:
173.2, 137.5, 135.7, 132.0, 130.4, 128.4, 128.2, 127.4,
121.5, 119.1, 118.8, 111.6, 109.5, 60.2, 38.4, 35.6, 20.1,
15.3, 14.1. Anal. calcd for C21H23NO2: C 78.47, H 7.21,
N 4.36; found C 78.29, H 7.11, N 4.54.
7
8
3-(1-Methyl-1H-indol-3-yl)propanal21 1H NMR
(CDCl3, 400 MHz) δ: 9.73 (t, J ＝2.6 Hz, 1H),
7.64—7.61 (m, 1H), 7.30—7.25 (m, 2H), 7.23—7.21
(m, 1H), 7.13—7.09 (m, 2H), 6.82 (s, 1H), 3.73 (s, 3H),
2.89—2.83 (m, 1H), 2.73—2.66 (m, 1H), 1.42 (d, J＝
7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ: 202.9,
125.1, 121.7, 119.0, 118.8, 109.4, 51.0, 32.6, 25.8, 21.6.
9
(a) Teo, Y.-C.; Loh, T.-P. Org. Lett. 2005, 7, 2539.
(b) Babu, G.; Perumal, P. T. Tetrahedron Lett. 1998, 39,
3225.
References
1
(a) Zhang, H.-C.; Ye, H.; Moretto, A. F.; Brumfield, K. K.;
Maryanoff, B. E. Org. Lett. 2000, 2, 89.
10 (a) For a review on the Friedel-Crafts reactions, see: Olah,
G. A.; Krishnamurti, R.; Prakash, G. K. S. In Comprehen-
sive Organic Synthesis, Vol. 3, Eds.: Trost, B. M.; Fleming,
I., Pergamon Press, Oxford, UK, 1991, pp. 293— 339.
(b) Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron Lett. 1998,
39, 6291.
11 Loh, T.-P.; Wei, L.-L. Tetrahedron Lett. 1998, 39, 323.
12 (a) Friestad, G. K.; Korapala, C. S.; Ding, H. J. Org. Chem.
2006, 71, 281.
(b) Faul, M. M.; Winneroski, L. L.; Krumrich, C. A. J. Org.
Chem. 1998, 63, 6053.
(c) Bennasar, M.-L.; Vidal, B.; Bosch, J. J. Org. Chem.
1997, 62, 3597.
(d) Tani, M.; Matsumoto, S.; Aida, Y.; Arikawa, S.; Nakane,
A.; Yokoyama, Y.; Murakami, Y. Chem. Pharm. Bull. 1994,
42, 443.
2
(a) Joule, J. A. In Science of Synthesis, Vol. 10, Ed.: Tho-
mas, E. J., Thieme, Stuttgart, 2000, pp. 361— 652.
(b) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000,
1045.
(b) Onishi, Y.; Ito, T.; Yasuda, M.; Baba, A. Eur. J. Org.
Chem. 2002, 1578.
13 Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G.
Synthesis 2001, 2165.
14 (a) Kumar, S.; Kumar, V.; Chimni, S. S. Tetrahedron Lett.
2002, 43, 8029.
(c) Moore, R. E.; Cheuk, C.; Yang, X. Q.; Patterson, G. M.
L.; Bonjouklian, R.; SmitKa, T. A.; Mynderse, J. S.; Foster,
R. S.; Jones, N. D.; Swartzendruber, J. K.; Deeter, J. B. J.
Org. Chem. 1987, 52, 1036.
(d) Garnick, R. L.; Levery, S. B.; Lequesne, P. W. J. Org.
Chem. 1978, 43, 1226.
(b) Kumar, S.; Kumar, V.; Chimni, S. S. Tetrahedron Lett.
2003, 44, 2101.
(c) Kumar, V.; Chimni, S. S.; Kumar, S. Tetrahedron Lett.
2004, 45, 3409.
(e) Moore, R. E.; Cheuk, C.; Patterson, G. M. L. J. Am.
Chem. Soc. 1984, 106, 6456.
15 Lopez-Alvarado, P.; Steinhoff, J.; Miranda, S.; Avendano,
C.; Menendez, J. C. Tetrahedron 2009, 65, 1660.
16 Maki, B. E.; Chan, A.; Phillips, E. M.; Scheidt, K. A. Tet-
rahedron 2009, 65, 3102.
17 González, A.; Pérez, D.; Puig, C.; Ryder, H.; Sanahuja, J.;
Solé, L.; Bach, J. Tetrahedron Lett. 2009, 50, 2750.
18 Friden-Saxin, M.; Pemberton, N.; Andersson, K. S.;
Dyrager, C.; Friberg, A.; Grøtli, M.; Luthman, K. J. Org.
Chem. 2009, 74, 2755.
19 Bandini, M.; Fagioli, M.; Garavelli, M.; Melloni, A.; Trigari,
V.; Umani-Ronchi, A. J. Org. Chem. 2004, 69, 7511.
20 Harrington, P. E.; Kerr, M. A. Synlett 1996, 1047.
21 Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem. Eur.
J. 2007, 13, 1358.
3
4
Bergmann, E. D.; Ginsburg, D.; Pappo, R. Organic Reac-
tions, Wiley, New York, 1959, 10, 179.
(a) Harrington, P. E.; Kerr, M. A. Can. J. Chem. 1998, 76,
1256.
(b) Harrington, P. E.; Kerr, M. A. Synlett 1996, 1047.
(a) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68,
2109.
5
(b) Bandini, M.; Cozzi, P. G.; Giacomini, M.; Melchiorre,
P.; Selva, S.; Umani-Ronchi, A. J. Org. Chem. 2002, 67,
3700.
(c) Bartoli, G.; Bartolacci, M.; Bosco, M.; Foglia, G.;
Giuliani, A.; Marcantoni, E.; Sambri, L.; Torregiani, E. J.
Org. Chem. 2003, 68, 4594.
(d) Alam, M. M.; Varala, R.; Adapa, S. R. Tetrahedron Lett.
2003, 44, 5115.
(E1003052 Cheng, B.; Dong, H.)
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