Synthesis of indolylquinolines, indolylacridines, and indolylcyclopenta[b] quinolines from the Baylis-Hillman adducts: An in situ [1,3]-sigmatropic rearrangement of an indole nucleus to access indolylacridines and indolylcyclopenta[b]quinolines

Article abstract of DOI:10.1021/jo301313m

A simple and easy route to the synthesis of a variety of structurally diverse indolylquinolines, indolylacridines, and indolylcyclopenta[b]quinoline derivatives via the reductive cyclization of C-alkylated indole derivatives, derived from acyclic as well as cyclic Baylis-Hillman adducts with indoles, is described. An unusual in situ [1,3]-sigmatropic rearrangement of the indole nucleus was observed during the reductive cyclicization of α- regioselective B-H adducts containing indoles to produce indolylacridines and indolylcyclopenta[b]quinoline derivatives.

Full text of DOI:10.1021/jo301313m

Article
pubs.acs.org/joc
Synthesis of Indolylquinolines, Indolylacridines, and
Indolylcyclopenta[b]quinolines from the Baylis−Hillman Adducts: An
in Situ [1,3]-Sigmatropic Rearrangement of an Indole Nucleus To
Access Indolylacridines and Indolylcyclopenta[b]quinolines
Chintakunta Ramesh, Po-Min Lei, Donala Janreddy, Veerababurao Kavala, Chun-Wei Kuo,
and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Section 4, Tingchow Road, Taipei, Taiwan 116, Republic of
China
S
* Supporting Information
ABSTRACT: A simple and easy route to the synthesis of a
variety of structurally diverse indolylquinolines, indolylacridines,
and indolylcyclopenta[b]quinoline derivatives via the reductive
cyclization of C-alkylated indole derivatives, derived from
acyclic as well as cyclic Baylis−Hillman adducts with indoles, is
described. An unusual in situ [1,3]-sigmatropic rearrangement
of the indole nucleus was observed during the reductive
cyclicization of α-regioselective B−H adducts containing
indoles to produce indolylacridines and indolylcyclopenta[b]-
quinoline derivatives.
concerning the synthesis of indolylacridines and
indolylcyclopenta[b]quinoline derivatives from B−H adducts.
However, the addition of indoles to acyclic B−H adducts as well
as cyclic B−H adducts has been reported.5a,9 As part of our
ongoing project on the synthesis of nitrogen-containing
heterocyclic molecules via reductive cyclization,5a,10 we report
herein on a convenient procedure for the synthesis of
indolylquinolines, indolylacridines, and indolylcyclopenta[b]-
quinoline derivatives.
INTRODUCTION
■
Indole, quinoline, and acridine structures are important nitrogen
heterocyclic motifs that are commonly found in a wide variety of
natural products, pharmaceuticals, and synthetic compounds that
are biologically active.1 Indolylquinolines are particularly
important, since they possess an array of biological activities,
including potent KDR (kinase insert domain receptor) kinase
inhibitors, male contraceptive activity in adult rats, antimicrobial
activity, and the dual inhibition of DNA topoisomerases of
Leishmania donovani and potent in vitro methicillin-resistant
Staphylococcus aureus.2 In addition, compounds bearing indole
and acridine moieties are key structural components in many
bioactive compounds and display interesting biological activ-
ities.3,4 There are, however, only a few approaches available for
the synthesis of indolylquinolines,2b,c,5and synthetic routes
leading to the production of indole−acridine hybrids are
rare.3,6 Hence, the synthesis of indolylquinolines as well as
indolylacridine derivatives using simple, straightforward ap-
proaches would be highly desirable.5a
The Baylis−Hillman (B−H) reaction is an atom-economical
and versatile carbon−carbon bond-forming reaction which
provides densely functionalized adducts.7 The use of B−H
adducts for the construction of various nitrogen-containing
heterocyclic molecules has been reported by several research
groups.8 To the best of our knowledge, only one report by our
group has appeared dealing with the synthesis of indolylquino-
lines from B−H adducts.5a There are no reports in the literature
RESULTS AND DISCUSSION
■
We recently reported on the C-alkylation of Baylis−Hillman
derivatives with indoles using iodine as a catalyst and the use of
the resulting C-alkylated indole derivatives in the synthesis of
indolylquinoline derivatives.5a In a continuation of this work, we
now report on the synthesis of a variety of indolylquinolines,
indolylacridines, and indolylcyclopenta[b]quinoline derivatives
in this paper. The outline for the synthesis of the indolylquino-
lines and indolylacridine derivatives is shown in Scheme 1.
To accomplish our objectives, we initially prepared a series of
B−H adducts from various o-nitrobenzaldehydes and methyl
vinyl ketone following reported procedures.11 The resulting B−
H adducts were then reacted with various indoles to give C-
Received: June 27, 2012
Published: September 12, 2012
© 2012 American Chemical Society
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Scheme 1. Synthetic Route to the Synthesis of Indolylquinolines, Indolylacridines, and Indolylcyclopenta[b]quinoline Derivatives
ab
,
Table 1. Addition of Indoles to Acyclic Baylis−Hillman Adducts
a
b
All the reactions were performed on a 2.0 mmol scale. Isolated yields.
alkylated indole derivatives in good yields under the previously
established conditions (Table 1, entries 1−16).5a
To further explore the scope of the methodology, we
investigated the C-alkylation of indoles with B−H alcohols
derived from various substituted 2-nitrobenzaldehydes and cyclic
enones (cyclohexenone and cyclopentenone). It has been
reported that the reaction of cyclic B−H acetates derived from
cyclic enones and indole in the presence of silver triflate resulted
in the production of α-selective addition products.9e We
therefore treated 2-methylindole with 2-(hydroxy(2-
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Table 2. Regioselective Addition of Indoles to Cyclic Baylis−Hillman Adducts
a
b
c
d
All the reactions were performed on a 2.0 mmol scale. Isolated yields. An 11% yield of γ-regioselective addition product 5d was isolated.
A
1
mixture of E/Z isomers was obtained, and the ratio of E to Z isomers was determined by H NMR studies of the crude products.
nitrophenyl)methyl)cyclohex-2-enone under our previously
established conditions, which were used in the case of acyclic
B−H adducts.5a Unfortunately, the reaction failed to produce the
α-regioselective product under the previously established
conditions. However, when the reaction was carried out with
30 mol % iodine in acetonitrile under reflux, the corresponding
product was produced in good yield. Hence, all reactions
involving cyclic B−H adducts were conducted under reflux
conditions. The results are summarized in Table 2. As shown in
Table 2, under the reaction conditions used, the reaction of 2-
methylindole with 2-(hydroxy(2-nitrophenyl)methyl)cyclohex-
2-enone, 2-((5-fluoro-2-nitrophenyl)hydroxymethyl)cyclohex-
2-enone, and 2-((5-chloro-2-nitrophenyl)hydroxymethyl)-
cyclohex-2-enone furnished the α-regioselective products 4a,
4b, and 4c in good yields (Table 2, entries 1−3). However, the
reaction of 2-((5-bromo-2-nitrophenyl)hydroxymethyl)-
cyclohex-2-enone with 2-methylindole produced α-regioselec-
tive product 4d along with traces of the γ-regioselective product
5d (Table 2, entry 4). On the other hand, the reaction of 2-
(hydroxy(2-nitrophenyl)methyl)cyclohex-2-enone with 2-phe-
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Figure 1. Crystal structures of the γ-regioselective E (5e) and Z (5e′) isomers.
Table 3. Regioselective Addition of Indoles to Cyclic Baylis−Hillman Adducts
a
b
All the reactions were performed on a 2.0 mmol scale. Isolated yields.
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a b
,
Table 4. Reductive Cyclization of C-Alkylated Indoles of Baylis−Hillman Adducts
a
b
All the reactions were performed on a 1.0 mmol scale. Isolated yields.
nylindole under the same reaction conditions afforded the γ-
regioselective product in a mixture of E and Z isomers 5e and 5e′
(Table 2, entry 5), which were separated by column
chromatography, the γ-regioselective E isomer 5e as the major
product and the γ-regioselective Z isomer 5e′ as a minor product,
phenylindole furnished the α-regioselective C-alkylated B−H
adduct 7e in good yield (Table 3, entry 5). It is noteworthy that
the reaction of 2-methylindole with various 2-(hydroxy(2-
nitrophenyl)methyl)cyclohex-2-enone derivatives afforded the
α-regioselective C-alkylated cyclic B−H adducts (Table 2, entries
1−4), whereas the reaction of 2-methylindole with various 2-
(hydroxy(2-nitrophenyl)methyl)cyclopent-2-enone derivatives
under similar reaction conditions furnished the γ-regioselective
C-alkylated cyclic B−H adducts (Table 3, entries 3 and 4).
However, the reaction of 2-phenylindole with various 2-
(hydroxy(2-nitrophenyl)methyl)cyclohex-2-enone derivatives
afforded the γ-regioselective C-alkylated cyclic B−H adducts
(Table 2, entries 5−8), and the reaction with 2-(hydroxy(2-
nitrophenyl)methyl)cyclopent-2-enone under the same reaction
conditions furnished the α-regioselective C-alkylated cyclic B−H
adduct (Table 3, entry 5).
After synthesizing the various substituted C-alkylated indole
derivatives from acyclic B−H and cyclic B−H alcohols
containing a nitro group in the second position, we then
subjected these C-alkylated indoles to reductive cyclization in the
presence of powdered Fe in acetic acid, and the results are
summarized in Table 4. As could be seen from Table 4, the
substrates containing electron-withdrawing groups as well as
electron-releasing groups reacted with equal ease to produce the
corresponding indolylquinoline derivatives in good to excellent
yields. It is interesting to note that, when 2-substituted indole
derivatives were used, product yields were excellent. It is also
noteworthy that chemoselective cyclization was achieved in the
presence of an ester group.
1
as evidenced by H NMR, 13C NMR, and HRMS analysis and
single-crystal X-ray analysis (Figure 1). Even the reactions of 2-
((5-fluoro-2-nitrophenyl)hydroxymethyl)cyclohex-2-enone, 2-
((5-chloro-2-nitrophenyl)hydroxymethyl)cyclohex-2-enone,
and 2-((5-bromo-2-nitrophenyl)hydroxymethyl)cyclohex-2-
enone with 2-phenylindole resulted in the formation of γ-
regioselective products in the form of a mixture of E and Z
isomers (Table 2, entries 6−8), which were not separated due to
the fact they eluted close to one another on the TLC plate.
However, the reaction of 2-(hydroxy(2-nitrophenyl)methyl)-
cyclohex-2-enone with indole and other indole derivatives did
not proceed under the above reaction conditions.
Encouraged by these results, we further explored the reactions
of cyclic B−H alcohols derived from various substituted 2-
nitrobenzaldehyde and cyclopent-2-enone derivatives with
substituted indoles in the presence of 30 mol % iodine in
acetonitrile under reflux conditions. The results are summarized
in Table 3. As shown in Table 3, the reaction of 2-(hydroxy(2-
nitrophenyl)methyl)cyclopent-2-enone with indole and 2-
methylindole afforded the γ-regioselective C-alkylated indole
derivatives 6a and 6c in good yields (Table 3, entries 1 and 3).
Interestingly, the reaction of N-methylindole and 2-methylindole
with 2-((5-fluoro-2-nitrophenyl)hydroxymethyl)cyclopent-2-
enone also produced the corresponding γ-regioselective C-
alkylated indole derivatives 6b and 6d in 79% and 91% yields,
respectively (Table 3, entries 2 and 4). Moreover, the reaction of
2-(hydroxy(2-nitrophenyl)methyl)cyclopent-2-enone with 2-
We next, investigated the reductive cyclization of C-alkylated
indole derivatives derived from cyclic B−H alcohols and indoles.
We expected that a 9-(2-methyl-1H-indol-3-yl)-2,3,4,9-tetrahy-
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droacridine derivative would be produced from the reductive
cyclization of the α-regioselective addition product 4a derived
from the reaction of 2-(hydroxy(2-nitrophenyl)methyl)-
cyclohex-2-enone and 2-methylindole. Surprisingly, the expected
9-(2-methyl-1H-indol-3-yl)-2,3,4,9-tetrahydroacridine deriva-
tive was not produced, and instead, 1-(2-methyl-1H-indol-3-
yl)-1,2,3,4-tetrahydroacridine was produced as the sole product
(Scheme 2). Encouraged by this result, we further tested the
Table 5. Synthesis of Indolylacridine Derivatives via
Reductive Cyclization
Scheme 2. Reaction of 2-((2-Methyl-1H-indol-3-yl)(2-
nitrophenyl)methyl)cyclohex-2-enone with Fe/AcOH
other α-regioselective addition products, derived from 2-
methylindole and various 2-(hydroxy(2-nitrophenyl)methyl)-
cyclohex-2-enone derivatives. In all cases, the corresponding1-
(2-methyl-1H-indol-3-yl)-1,2,3,4-tetrahydroacridine derivatives
8a−8d were produced in good to excellent yields (Table 5,
entries 1−4).
On the other hand, the reductive cyclization of γ-regioselective
addition products (E and Z mixture) derived from various
substituted 2-(hydroxy(2-nitrophenyl)methyl)cyclohex-2-
enone and 2-phenylindole derivatives resulted in the formation
of the corresponding 1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-tetra-
hydroacridine derivatives 8e−8h in good yields (Table 5, entries
5−8). It is important to note that the reductive cyclization of α-
regioselective addition products derived from various substituted
2-(hydroxy(2-nitrophenyl)methyl)cyclohex-2-enone derivatives
with 2-methylindole as well as γ-regioselective addition products
(E and Z mixture) derived from various substituted 2-
(hydroxy(2-nitrophenyl)methyl)cyclohex-2-enone derivatives
with 2-phenylindole produced the same structural motif under
the reaction conditions employed (Table 5, entries 1−8). The
products were characterized by 1H NMR, 13C NMR, and HRMS
analyses. The crystal structures of representative compounds 4a
and 8a are shown in Figure 2.
a
b
All the reactions were performed on a 1.0 mmol scale. A mixture of
c
the products was subjected to reductive cyclization. Isolated yields.
Consequently, we examined the reductive cyclization of γ-
regioselective addition products derived from various 2-
(hydroxy(2-nitrophenyl)methyl)cyclopent-2-enone and indole
derivatives, including indole, N-methylindole, and 2-methyl-
indole, in the presence of powdered Fe in acetic acid at 80 °C.
Under these conditions the reactions afforded the corresponding
1-(1H-indol-3-yl)-2,3-dihydro-1H-cyclopenta[b]quinoline de-
rivatives 8i−8l in good yields (Table 6, entries 1−4). Even the
reductive cyclization of the α-regioselective addition product
derived from 2-(hydroxy(2-nitrophenyl)methyl)cyclopent-2-
enone with 2-phenylindole produced the similar structural
motif 8m in moderate yield (Table 6, entry 5).
The mechanistic pathways for the formation of indolylacridine
derivatives from both the regioselective adducts are depicted in
Scheme 3. As shown in Scheme 3, the formation of
indolylacridine derivatives from γ-regioselective adducts 5d−
5h, 5e′−5h′, and 6a−6d involves straightforward reductive
cyclization. However, formation of indolylacridine derivatives
8a−8d and 8m from the α-regioselective adducts 4a−4d and 7e
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Figure 2. Crystal structures of 4a and 8a.
Table 6. Synthesis of Indolylcyclopenta[b]quinoline Derivatives via Reductive Cyclization
a
b
All the reactions were performed on a 1.0 mmol scale at 80 °C. Isolated yields.
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Scheme 3. Plausible Mechanism for the Formation of Indolylacridine Derivatives from the α-Regioselective and γ-Regioselective
Adducts
Scheme 4. Short Route for the Synthesis of 3-((1H-Indol-1-yl)methyl)-2-methylquinoline (3qb)
may proceed through an unusual in situ [1,3]-sigmatropic
rearrangement of the indole nucleus during the reaction. In fact,
similar types of [1,3]-sigmatropic regarrangements are known in
the literature. Recently, Liu et al. observed the [1,3]-sigmatropic
rearrangement of an indole nucleus in the presence of a catalytic
amount of iodine in trifluoroethanol under reflux conditions.9f In
this protocol, they found that the indole moiety migrated from
the γ-position to the α-position. In another protocol, Chen et. al
observed an in situ [1,3]-sigmatropic rearrangement of the
phenyl group during the formation of 4,10-dihydropyrimido[1,2-
a]benzimidazoles from a base-catalyzed Povarov reaction of
arylamines, aldehydes, and electron-deficient dienophiles.12
Baylis−Hillman acetates and the N-alkylation of an indole with
B−H acetate were carried out using a previously reported
procedure.8e,9d Subsequently, we were able to smoothly
reductively cyclize the product 3q to compound 3qb in good
yield in the presence of Fe/AcOH under reflux conditions
(Scheme 4). Compound 3qb was synthesized in a previous
study, but multiple steps were involved.13 Using our protocol, the
preparation was much more efficient.
production of indolylquinolines, indolylacridines, and
indolylcyclopenta[b]quinoline derivatives. During the reductive
cyclization of α-regioselective cyclic B−H adducts containing
indoles, we observed an unusual in situ [1,3]-sigmatropic
rearrangement of the indole nucleus with the production of
more stable indolylacridines and indolylcyclopenta[b]quinoline
derivatives.
EXPERIMENTAL SECTION
■
Reagents and solvents were purchased from various commercial sources
and used directly without any further purification unless otherwise
stated. Column chromatography was performed on 63−200 mesh silica
1
gel. H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively. Chemical shifts were made in reference to NMR solvent
signals (CDCl3 or DMSO-d6), and coupling constants are expressed in
hertz. Mass spectra were recorded using the EI+ mode, and data are
reported as the mass/charge (m/z) ratio with the percent relative
abundance. High-resolution mass spectrometry (HRMS) was per-
formed on an electron ionization time-of-flight (EI-TOF) mass
spectrometer. Melting points were recorded using a capillary melting
point apparatus and are uncorrected.
General Procedure for the Synthesis of 3a−3p. To a stirred
solution of the Baylis−Hillman alcohol (2.0 mmol, 1.0 equiv) in
acetonitrile (10.0 mL) were added indole (2.8 mmol, 1.4 equiv) and
iodine (0.3 equiv), and the mixture was stirred until the reaction was
complete, as monitored by TLC. The reaction mixture was quenched
with a saturated solution of sodium thiosulfate and extracted with ethyl
acetate (2.0 × 10.0 mL). The organic layer was separated, dried over
anhydrous magnesium sulfate, and concentrated to give the crude
In conclusion, we report on the successful development of a
simple and facile protocol for the synthesis of indolylquinolines,
indolylacridines, and indolylcyclopenta[b]quinoline derivatives
from Baylis−Hillman adducts. The protocol involves two steps.
The first step involves the addition of indoles to acyclic and cyclic
Baylis−Hillman adducts, and in the second step, the resulting
products are subjected to reductive cyclization, with the
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product. All of the crude products were purified by passing them
through a short silica gel column (ethyl acetate/hexane).
Data for (E)-3-((5-chloro-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)-
but-3-en-2-one (3g): yield 587 mg (83%); yellow solid; mp 128−130
°C; 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.99 (br s,
1H), 7.93 (s, 1H), 7.61−7.57 (m, 1H), 7.54−7.50 (m, 1H), 7.37 (d, J =
7.5 Hz, 1H), 7.19 (d, J = 8.5 Hz, 1H), 7.11−7.06 (m, 2H), 6.81 (s, 1H),
3.70 (s, 2H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 147.4,
141.1, 137.4, 134.5, 133.9, 131.7, 130.9, 129.6, 128.0, 125.2, 125.1, 123.6,
122.4, 118.1, 113.4, 112.2, 26.5, 22.1; MS (EI) m/z (relative intensity)
354 (M+, 20), 311 (23), 295 (100), 294 (16); HRMS (EI) m/z calcd for
C19H15ClN2O3 (M+) 354.0771, found 354.0775.
Data for 3-((5-bromo-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)-
but-3-en-2-one (3h): yield 644 mg (81%); yellow solid; mp 122−123
°C; 1H NMR (400 MHz, CDCl3) δ 8.14 (dd, J = 8.1, 1.0 Hz, 1H), 8.0 (br
s, 1H), 7.93 (s, 1H), 7.61−7.57 (m, 1H), 7.54−7.50 (m, 1H), 7.36 (d, J =
7.4 Hz, 1H), 7.25 (s, 1H), 7.19 (dd, J = 8.5, 1.7 Hz, 1H), 7.14 (d, J = 8.6
Hz, 1H), 6.79 (s, 1H), 3.69 (s, 2H), 2.50 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 199.7, 147.5, 141.2, 137.3, 134.8, 133.9, 131.8, 130.9, 129.6,
128.7, 125.2, 125.0, 123.5, 121.3, 113.5, 112.7, 112.7, 26.5, 22.0; MS (EI)
m/z (relative intensity) 400 (M+ + 2, 9), 398 (M+, 8), 354 (24), 340
(100), 310 (13), 297 (2), 259 (49) 228 (32), 208 (50), 207 (33), 195
(17), 187 (6), 128 (30), 101 (131), 74 (2); HRMS (EI) m/z calcd for
C19H1579BrN2O3 (M+) 398.0261, found 398.0258; HRMS (EI) m/z
calcd for C19H1581BrN2O3 (M+) 400.0240, found 400.0242.
Data for 3-((1H-indol-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-
one (3a): yield 544 mg (85%); yellow solid; mp 135−136 °C; 1H NMR
(400 MHz, CDCl3) δ 8.12 (dd, J = 8.1, 1.0 Hz, 1H), 7.99 (br s, 1H), 7.94
(s, 1H), 7.53−7.47 (m, 2H), 7.40 (d, J = 7.5 Hz, 1H), 7.34−7.28 (m,
2H), 7.16 (t, J = 7.3 Hz, 1H), 7.04 (t, J = 7.3 Hz, 1H), 6.75 (s, 1H), 3.79
(s, 2H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 200.1, 147.6,
141.3, 136.7, 136.4, 133.8, 131.9, 131.0, 129.4, 127.0, 125.1, 122.0, 119.5,
118.7, 114.8, 113.9, 111.2, 26.7, 22.6; MS (EI) m/z (relative intensity)
320 (M+, 18), 276 (31), 261 (50), 260 (100), 230 (33), 202 (16);
HRMS (EI) m/z calcd for C19H16N2O3 (M+) 320.1155, found
320.1153.
Data for 3-((2-methyl-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)-
but-3-en-2-one (3b): yield 568 mg (85%); yellow solid; mp 97−99
°C; 1H NMR (400 MHz, CDCl3) δ 8.01 (dd, J = 8.1, 0.9 Hz, 1H), 7.83
(s, 1H), 7.60 (br s, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.37−7.32 (m, 2H),
7.12−7.10 (m, 2H), 7.10−7.01 (m, 1H), 6.93−6.91 (m, 1H) 3.77 (s,
2H), 2.45 (s, 3H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 200.5,
147.0, 142.0, 136.1, 135.1, 133.3, 131.9, 131.8, 131.0, 128.9, 128.3, 124.8,
120.8, 119.1, 118.0, 110.1, 108.1, 26.6, 21.8, 11.7; MS (EI) m/z (relative
intensity) 335 (M+ + 1, 15), 333 (81), 290 (33), 275 (72), 274 (80), 244
(20), 183 (15), 158 (46), 143 (100), 129 (79), 126 (15); HRMS (EI)
m/z calcd for C20H18N2O3 (M+) 334.1312, found 334.1317.
Data for methyl 3-(2-(2-nitrobenzylidene)-3-oxobutyl)-1H-indole-
2-carboxylate (3c): yield 597 mg (79%); colorless solid; mp 149−150
°C; 1H NMR (400 MHz, CDCl3) δ 8.55 (br s, 1H), 7.87 (s, 1H), 7.81
(dd, J = 8.2, 1.0 Hz, 1H), 7.35−7.31 (m, 2H), 7.21−7.18 (m, 4H), 7.15−
6.97 (m, 1H), 4.21 (s, 2H), 3.82 (s, 3H), 2.55 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 199.7, 162.0, 146.3, 141.5, 137.7, 135.7, 133.0, 131.9,
130.5, 128.6, 127.4, 125.7, 124.3, 123.2, 121.3, 121.2, 120.2, 111.6, 51.7,
26.3, 22.3; MS (EI) m/z (relative intensity) 378 (M+, 60), 361 (27), 318
(59), 286 (57), 258 (62), 228 (32), 188 (100), 187 (80), 155 (53), 127
(40), 101 (15); HRMS (EI) m/z calcd for C21H18N2O5 (M+) 378.1210,
found 378.1210.
Data for (E)-methyl 1-methyl-3-(2-(2-nitrobenzylidene)-3-oxobu-
tyl)-1H-indole-2-carboxylate (3d): yield 635 mg (81%); pale brown
solid; mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.73
(d, J = 8.2 Hz, 1H), 7.30−7.28 (m, 1H), 7.25−7.23 (m, 1H), 7.22−7.14
(m, 2H), 7.12−7.08 (m, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.95 (t, 7.4 Hz,
1H), 4.15 (s, 2H), 3.82 (s, 3H), 3.79 (s, 3H), 2.56 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 199.7, 162.5, 142.1, 138.3, 137.4, 132.7, 131.9,
130.2, 128.0, 126.2, 125.2, 124.8, 123.9, 121.7, 120.9, 119.9, 114.7, 109.8,
51.4, 31.9, 26.3, 22.9; MS (EI) m/z (relative intensity) 392 (M+, 32),
333 (100), 332 (83), 273 (30), 202 (98), 189 (39); HRMS (EI) m/z
calcd for C22H20N2O5 (M+) 392.1367, found 392.1384.
Data for 4-(2-nitrophenyl)-3-((2-phenyl-1H-indol-3-yl)methyl)-
but-3-en-2-one (3e): yield 665 mg (84%); red solid; mp 134−135
°C; 1H NMR (400 MHz, CDCl3) δ 7.87−7.85 (m, 2H), 7.76 (s, 1H),
7.41−7.38 (m, 4H), 7.36−7.28 (m, 3H), 7.25−7.19 (m, 2H), 7.14−7.07
(m, 2H), 6.98 (t, J = 7.5 Hz, 1H), 4.05 (s, 2H), 2.36 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 200.5, 146.5, 142.0, 136.7, 135.8, 134.8, 133.0,
132.9, 131.7, 130.5, 128.8, 128.7, 128.3, 127.8, 124.6, 122.3, 119.7, 119.5,
110.7, 110.7, 109.8, 26.4, 22.4; MS (EI) m/z (relative intensity) 396
(M+, 23) 362 (10), 353 (30), 336 (51), 318 (42), 305 (12), 229 (13),
216 (22), 203 (100), 193 (85), 178 (22), 151 (7); HRMS (EI) m/z
calcd for C25H20N2O3 (M+) 396.1468, found 396.1461.
Data for 3-((5-methoxy-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)-
but-3-en-2-one (3f): yield 560 mg (80%); yellow solid; mp 133−134
°C; 1H NMR (400 MHz, CDCl3) δ 8.13 (dd, J = 8.1, 1.2 Hz, 1H), 7.93
(s, 1H), 7.86 (br s, 1H), 7.54−7.52 (m, 1H), 7.49−7.47 (m, 1H), 7.41
(d, J = 7.5 Hz, 1H), 7.18 (d, J = 8.6 Hz, 1H), 6.83−6.78 (m, 2H), 6.73 (s,
1H), 3.79 (s, 3H), 3.74 (s, 2H), 2.49 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 200.0, 154.1, 147.6, 141.4, 136.6, 133.8, 131.9, 131.5, 131.1,
129.4, 127.4, 125.1, 122.8, 113.6, 112.6, 112.0, 100.6, 56.0, 26.7, 22.7;
MS (EI) m/z (relative intensity) 350 (M+, 47), 315 (8), 306 (33), 290
(100), 248 (23), 247 (29), 217 (25), 188 (19), 159 (48), 147 (35), 132
(22), 117 (11), 89 (6); HRMS (EI) m/z calcd for C20H18N2O4 (M+)
350.1261, found 350.1254.
Data for (E)-3-((5-fluoro-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)-
but-3-en-2-one (3i): yield 568 mg (84%); red solid; mp 116−118 °C;
1H NMR (400 MHz, CDCl3) δ 8.21 (br s, 1H), 8.11 (d, J = 7.8 Hz, 1H),
7.94 (s, 1H), 7.57−7.46 (m, 2H), 7.37 (d, J = 7.2 Hz, 1H), 7.17−7.14
(m, 1H), 6.89−6.83 (m, 2H), 6.76 (s, 1H), 3.70 (s, 2H), 2.50 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 200.0, 157.7 (d, J = 233.0 Hz), 147.4,
141.1, 137.2, 133.8, 132.7, 131.7, 130.9, 129.5, 127.2 (d, J = 10.0 Hz),
125.1, 124.0, 113.8 (d, J = 5.0 Hz), 111.9 (d, J = 10.0 Hz), 110.4 (d, J =
26.0 Hz), 103.5 (d, J = 23.0 Hz), 26.5, 22.3; MS (EI) m/z (relative
intensity) 338 (M+, 53), 294 (21), 279 (100); HRMS (EI) m/z calcd for
C19H15FN2O3 (M+) 338.1067, found 338.1075.
Data for 3-((7-ethyl-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)but-
3-en-2-one (3j): yield 577 mg (83%); brown gummy liquid; 1H NMR
(400 MHz, CDCl3) δ 8.12 (dd, J = 8.0, 1.2 Hz, 1H), 7.94 (s, 1H), 7.92
(br s, 1H), 7.53−7.51 (m, 1H), 7.49−7.46 (m, 1H), 7.41 (d, J = 7.5 Hz,
1H), 7.21−7.19 (m, 1H), 7.01−7.00 (m, 2H), 6.77 (s, 1H), 3.79 (s, 2H),
2.81 (q, J = 7.6 Hz, 2H), 2.49 (s, 3H), 1.33 (t, J = 7.5 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 200.1, 147.5, 141.2, 136.5, 135.2, 133.8, 131.8,
131.0, 129.3, 126.7, 126.6, 125.0, 121.7, 120.7, 119.7, 116.4, 114.1, 26.7,
24.0, 22.8, 13.9; MS (EI) m/z (relative intensity) 348 (M+, 38), 304
(39), 288 (100), 287 (56), 259 (39), 243 (18), 240 (112), 187 (10), 157
(30), 142 (19), 129 (13), 115 (8); HRMS (EI) m/z calcd for
C21H20N2O3 (M+) 348.1468, found 348.1480.
Data for (E)-3-((1-methyl-1H-indol-3-yl)methyl)-4-(2-
nitrophenyl)but-3-en-2-one (3k): yield 554 mg (83%); red solid; mp
1
240−242 °C; H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 8.0, 0.9
Hz,1H), 7.95 (s, 1H), 7.56−7.50 (m, 2H), 7.43 (d, J = 7.4 Hz, 1H), 7.33
(d, J = 7.9 Hz, 1H), 7.28 (d, J = 4.8 Hz, 1H), 7.23−7.19 (m, 1H), 7.07−
7.04 (m, 1H), 6.66 (s, 1H), 3.80 (s, 2H), 3.71 (s, 3H), 2.53 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 200.0, 147.7, 141.6, 137.1, 136.4, 133.7,
131.9, 131.1, 129.3, 127.4, 126.9, 125.0, 121.8, 118.9, 118.8, 112.2, 109.3,
32.8, 26.7, 22.6; MS (EI) m/z (relative intensity) 335 (M+, 30), 334
(90), 291 (58), 275 (100), 274 (39), 247 (17), 131 (19); HRMS (EI)
m/z calcd forC20H18N2O3 (M+) 334.1317, found 334.1325.
Data for (E)-3-((1H-indol-3-yl)methyl)-4-(5-chloro-2-nitrophenyl)-
but-3-en-2-one (3l): yield 609 mg (86%); yellow solid; mp 165−167
°C; 1H NMR (400 MHz, DMSO-d6) δ 10.76 (br s, 1H), 8.16 (d, J = 8.8
Hz, 1H), 7.92 (s, 1H), 7.67 (dd, J = 8.8, 1.7 Hz, 1H), 7.55 (s, 1H), 7.28−
7.24 (m, 2H), 7.04−7.01 (m, 1H), 6.91−6.87 (m, 1H), 6.78 (s, 1H),
3.66 (s, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 199.6, 145.6,
142.0, 140.2, 136.2, 135.4, 133.7, 130.8, 129.3, 126.8, 126.4, 122.3, 122.1,
119.6, 118.6, 113.4, 111.2, 26.6, 22.5; MS (EI) m/z (relative intensity)
354 (M+, 29), 311 (36), 295 (100), 294 (52), 116 (13); HRMS (EI) m/z
calcd forC19H15ClN2O3 (M+) 354.0771, found 354.0769.
Data for (E)-3-((1H-indol-3-yl)methyl)-4-(5-bromo-2-
nitrophenyl)but-3-en-2-one (3m): yield 676 mg (85%); yellow solid;
mp 136−138 °C; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.7 Hz,
8459
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Article
1H), 7.90 (br s, 1H), 7.82 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.48−7.46
(m, 1H), 7.30−7.27 (m, 2H), 7.16−7.12 (m, 1H), 7.06−7.02 (m, 1H),
6.74 (s, 1H), 3.78 (s, 2H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.6, 145.3, 136.7, 134.3, 134.2, 132.2, 130.2, 129.3, 128.7, 127.4, 122.9,
122.6, 119.9, 119.5, 119.0, 113.4, 111.5, 29.2, 23.5; MS (EI) m/z
(relative intensity) 398 (M+, 36), 355 (30), 339 (100), 117 (25); HRMS
(EI) m/z calcd for C19H1579BrN2O3 (M+) 398.0266, found 398.0273;
HRMS (EI) m/z calcd for C19H1581BrN2O3 (M+) 400.0246, found
400.0263.
Data for (E)-3-((1H-indol-3-yl)methyl)-4-(5-fluoro-2-nitrophenyl)-
but-3-en-2-one (3n): yield 588 mg (87%); yellow solid; mp 134−136
°C; 1H NMR (400 MHz, CDCl3) δ 8.17−8.13 (m, 1H), 7.92 (br s, 1H),
7.86 (s, 1H), 7.33−7.26 (m, 2H), 7.17−7.04 (m, 4H), 6.76−6.75 (m,
1H), 3.79 (s, 2H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 199.7,
164.8 (d, J = 258.0 Hz), 143.6, 141.7, 136.3, 135.6, 135.1 (d, J = 10.0
Hz), 128.0 (d, J = 10.0 Hz), 126.8, 122.4, 122.0, 119.6, 118.6, 117.9 (d, J
= 24.0 Hz), 116.3 (d, J = 23.0 Hz), 113.4, 111.2, 26.6, 22.6; MS (EI) m/z
(relative intensity) 338 (M+, 53), 295 (38), 279 (100), 117 (10); HRMS
(EI) m/z calcd for C19H15FN2O3 (M+) 338.1067, found 338.1063.
Data for (E)-3-((1H-indol-3-yl)methyl)-4-(5-methoxy-2-
nitrophenyl)but-3-en-2-one (3o): yield 462 mg (66%); yellow solid;
mp 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 8.06 (br
s, 1H), 7.93 (s, 1H), 7.32−7.27 (m, 3H), 7.20−7.16 (m, 1H), 7.09−7.05
(m, 1H), 6.86 (s, 1H), 6.77 (s, 1H), 3.77 (s, 2H), 3.21 (s, 3H), 2.59 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 199.4, 155.9, 142.4, 138.9, 138.3,
137.7, 136.2, 135.6, 126.4, 123.6, 122.9, 122.0, 120.1, 118.4, 115.3, 114.2,
111.4, 56.7, 26.6, 23.2; LRMS (FAB) m/z (relative intensity) 350 (M+,
12), 245 (100), 154 (100), 136 (57), 107 (28); HRMS (FAB) m/z calcd
for C20H18N2O4 (M+) 350.1267, found 350.1261.
Data for (E)-3-((1H-indol-3-yl)methyl)-4-(4,5-dimethoxy-2-
nitrophenyl)but-3-en-2-one (3p): yield 539 mg (71%); yellow solid;
mp 130−132 °C; 1H NMR (400 MHz, CDCl3) δ 8.07 (br s, 1H), 8.01
(s, 1H), 7.72 (s, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H),
7.17−7.14 (m, 1H), 7.07−7.04 (m, 1H), 6.79 (d, J = 1.0 Hz, 1H), 6.71
(s, 1H), 3.94 (s, 3H), 3.78 (s, 2H), 3.14 (s, 3H), 2.51 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 200.1, 153.2, 148.9, 140.3, 140.1, 138.2, 136.3,
126.8, 126.4, 122.5, 121.9, 119.7, 118.7, 114.8, 112.0, 111.2, 107.9, 56.5,
55.7, 26.6, 23.1; LRMS (FAB) m/z (relative intensity) 381 (M+ + 1,
100), 337 (52), 321 (72); HRMS (FAB) m/z calcd for C21H20N2O5 (M
+ H)+ 381.1450, found 381.1451.
Data for (E)-3-((1H-indol-1-yl)methyl)-4-(2-nitrophenyl)but-3-en-
2-one (3q): yield 505 mg (79%); brown gummy liquid; 1H NMR (400
MHz, CDCl3) δ 8.12−8.10 (m, 1H), 8.07 (s, 1H), 7.48−7.43 (m, 3H),
7.09−7.00 (m, 3H), 6.89 (d, J = 7.8 Hz, 1H), 6.83−6.82 (m, 1H), 6.32−
6.31 (m, 1H), 4.97 (s, 2H), 2.51 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 198.8, 146.7, 140.7, 137.6, 136.0, 133.8, 130.5, 130.4, 129.8, 128.5,
127.4, 125.2, 121.6, 120.9, 119.6, 109.3, 102.2, 41.3, 26.4; MS (EI) m/z
(relative intensity) 320 (M+, 100) 117 (26); HRMS (EI) m/z calcd for
C19H16N2O3 (M+) 320.1155, found 320.1157.
232 (8), 154 (9), 153 (14), 129 (26), 114 (8); HRMS (EI) m/z calcd for
C19H16N2 (M+) 272.1308, found 272.1302.
Data for 2-methyl-3-((2-methyl-1H-indol-3-yl)methyl)quinoline
(3bb): yield 237 mg (83%); colorless solid; mp 210−211 °C; 1H
NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.4 Hz, 1H), 7.97 (br s, 1H),
7.61−7.54 (m, 3H), 7.39−7.34 (m, 2H), 7.28 (d, J = 7.9 Hz, 1H), 7.14
(t, J = 7.4 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H), 4.16 (s, 2H), 2.83 (s, 3H),
2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.6, 145.7, 135.4, 133.5,
132.9, 128.3, 127.7, 127.1, 126.8, 125.5, 120.0, 118.2, 117.5, 110.5, 106.3,
27.1, 23.2, 11.4; MS (EI) m/z (relative intensity) 285 (M+, 100), 270
(48), 267 (9), 154 (9), 153 (11), 143 (52), 129 (14), 115 (6); HRMS
(EI) m/z calcd for C20H18N2 (M+) 286.1465, found 286.1465.
Data for methyl 3-((2-methylquinolin-3-yl)methyl)-1H-indole-2-
carboxylate (3cb): yield 260 mg (79%); yellow solid; mp 224−225 °C;
1H NMR (400 MHz, CDCl3) δ 9.03 (br s, 1H), 8.00 (d, J = 8.4 Hz, 1H),
7.58 (t, J = 7.6 Hz, 1H), 7.51−7.42 (m, 4H), 7.37−7.33 (m, 2H), 7.07 (t,
J = 7.6 Hz, 1H), 4.63 (s, 2H), 3.86 (s, 3H), 2.88 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 162.6, 158.6, 146.4, 136.3, 134.2, 133.0, 128.7, 128.3,
128.2, 127.5, 127.3, 126.1, 125.7, 124.3, 121.2, 120.8, 120.5, 112.2, 52.1,
28.0, 23.8; MS(EI) m/z (relative intensity) 330 (M+, 100), 298 (24),
271 (85), 256 (25), 227 (8), 156 (8), 149 (16), 134 (20), 101 (18);
HRMS (EI) m/z calcd for C21H18N2O2 (M+) 330.1363, found
330.1361.
Data for methyl 1-methyl-3-((2-methylquinolin-3-yl)methyl)-1H-
indole-2-carboxylate (3db): yield 264 mg (77%); white solid; mp 191−
193 °C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 1H), 7.59−
7.55 (m, 1H), 7.49−7.45 (m, 3H), 7.42−7.32 (m, 3H), 7.10 (t, J = 7.0
Hz, 1H), 4.57 (s, 2H), 4.12 (s, 3H), 3.77 (s, 3H), 2.88 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 163.0, 158.4, 146.4, 139.1, 133.7, 133.4, 128.6,
128.3, 127.5, 127.3, 127.0, 125.9, 125.7, 125.6, 120.9, 120.7, 120.6, 110.5,
51.7, 32.5, 28.5, 23.9; MS (EI) m/z (relative intensity) 344 (M+, 100),
285 (30); HRMS (EI) m/z calcd for C22H20N2O2 (M+) 344.1519, found
344.1528.
Data for 2-methyl-3-((2-phenyl-1H-indol-3-yl)methyl)quinoline
1
(3eb): yield 278 mg (80%); brown solid; mp 254−255 °C; H NMR
(400 MHz, CDCl3) δ 8.40 (br s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.67 (s,
1H), 7.63−7.59 (m, 1H), 7.54−7.43 (m, 2H), 7.40−7.34 (m, 7H),
7.27−7.24 (m, 1H), 7.10−7.06 (m, 1H), 4.32 (s, 2H), 2.82 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.8, 146.5, 136.4, 136.2, 134.4, 133.3,
132.8, 129.5, 129.2, 128.8, 128.3, 128.1, 127.7, 127.6, 127.5, 125.7, 122.8,
120.2, 119.5, 111.2, 109.1, 28.2, 23.7; MS (EI) m/z (relative intensity)
348 (M+, 62), 347 (100), 333 (7), 270 (6), 206 (79), 192 (35), 173 (17),
151 (11); HRMS (EI) m/z calcd for C25H20N2 (M+) 348.1621, found
348.1625.
Data for 3-((5-methoxy-1H-indol-3-yl)methyl)-2-methylquinoline
1
(3fb): yield 235 mg (78%); brown solid; mp 185−186 °C; H NMR
(400 MHz, CDCl3) δ 8.08 (br s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.82 (s,
1H), 7.66−7.60 (m, 2H), 7.43 (t, J = 7.5 Hz, 1H), 7.28 (d, J = 8.7 Hz,
1H), 6.96−6.95 (m, 1H), 6.89 (dd, J = 8.7, 2.3 Hz, 1H), 6.79−6.78 (m,
1H), 4.20 (s, 2H), 3.80 (s, 3H), 2.76 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.1, 154.3, 146.7, 135.4, 133.0, 131.9, 128.8, 128.3, 127.9,
127.6, 127.3, 125.8, 123.7, 113.5, 112.6, 112.2, 100.9, 56.1, 29.2, 23.5;
MS (EI) m/z (relative intensity) 301 (M+ −1, 100), 300 (45), 286 (24),
257 (7), 159 (19), 127 (6); HRMS (EI) m/z calcd for C20H18N2O (M+)
302.1414, found 302.1419.
General Procedure for the Synthesis of 3ab−3qb. To a stirred
solution of C-alkylated acyclic Baylis−Hillman adducts containing
indole moieties (1.0 mmol) in acetic acid (5.0 mL) was added powdered
Fe (6.0 mmol, 6.0 equiv), and the reaction mixture was then refluxed for
2 h. The mixture was cooled to room temperature, the acetic acid was
removed under reduced pressure, and EtOAc (10.0 mL) was added. The
resulting mixture was stirred for 2 min and the solution filtered to
remove any iron impurities. The insoluble iron residue was washed with
EtOAc (10.0 mL). The filtrate and washings were combined and dried
over anhydrous MgSO4. The solvent was removed under reduced
pressure, and all of the crude products were purified by passing them
through a short silica gel column (ethyl acetate/hexane).
Data for 3-((1H-indol-3-yl)methyl)-2-methylquinoline (3ab): yield
206 mg (76%); colorless solid; mp 180−181 °C; 1H NMR (400 MHz,
CDCl3) δ 8.20 (br s, 1H), 8.02 (d, J = 8.3 Hz, 1H), 7.83 (s, 1H), 7.66−
7.60 (m, 2H), 7.54 (d, J = 7.8 Hz, 1H), 7.44−7.38 (m, 2H), 7.24−7.21
(m, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.80 (s, 1H), 4.25 (s, 2H), 2.75 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 159.1, 146.7, 136.7, 135.4, 133.1, 128.8,
Data for 3-((5-chloro-1H-indol-3-yl)methyl)-2-methylquinoline
1
(3gb): yield 235 mg (77%); yellow solid; mp 217−219 °C; H NMR
(400 MHz, CDCl3) δ 8.12 (br s, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.80 (s,
1H), 7.67−7.62 (m, 2H), 7.51 (d, J = 1.8 Hz, 1H), 7.46−7.42 (m, 1H),
7.32 (d, J = 8.6 Hz, 1H), 7.18 (dd, J = 8.6, 1.9 Hz, 1H), 6.82 (d, J = 1.9
Hz, 1H), 4.20 (s, 2H), 2.74 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
158.6, 145.8, 134.8, 134.1, 133.3, 128.4, 128.1, 127.8, 127.1, 126.8, 125.7,
125.6, 123.1, 121.0, 117.6, 113.0, 111.5, 28.0, 23.0; MS (EI) m/z
(relative intensity) 308 (M+, 56), 306 (100); HRMS (EI) m/z calcd
forC19H15ClN2 (M+) 306.0924, found 306.0917.
Data for 3-((5-bromo-1H-indol-3-yl)methyl)-2-methylquinoline
1
(3hb): yield 252 mg (72%); brown solid; mp 192−193 °C; H NMR
(400 MHz, CDCl3) δ 8.22 (br s, 1H), 8.02 (d, J = 8.3 Hz, 1H), 7.79 (s,
1H), 7.68−7.62 (m, 3H), 7.46−7.42 (m, 1H), 7.32−7.28 (m, 2H),
6.80−6.79 (m, 1H), 4.19 (s, 2H), 2.73 (s, 3H); 13C NMR (100 MHz,
128.3, 127.6, 127.5, 127.3, 125.8, 122.9, 122.4, 119.7, 119.0, 113.8, 111.5,
29.2, 23.5; MS (EI) m/z (relative intensity) 271 (M+, 100), 257 (22),
8460
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CDCl3) δ 158.9, 146.7, 135.5, 135.3, 132.6, 129.3, 129.0, 128.2, 127.5,
127.3, 126.0, 125.3, 124.2, 121.6, 113.5, 113.0, 113.0, 29.0, 23.4; MS (EI)
m/z (relative intensity) 352 (M+ + 2, 68), 350 (M+, 100), 347 (13), 334
(12), 269 (3), 267 (20), 227 (13), 208 (25), 200 (10), 154 (23), 153
(35), 134 (55), 114 (20), 101 (12); HRMS (EI) m/z calcd for
C19H1579BrN2 (M+) 350.0413, found 350.0408; HRMS (EI) m/z calcd
for C19H1581BrN2 (M+) 352.0393, found 352.0392.
Data for 3-((1H-indol-3-yl)methyl)-6-methoxy-2-methylquinoline
1
(3ob): yield 202 mg (67%); yellow solid; mp 184−186 °C; H NMR
(400 MHz, CDCl3) δ 8.19 (br s, 1H), 7.63 (s, 1H), 7.54 (d, J = 7.8 Hz,
1H), 7.40 (d, J = 8.1 Hz, 1H), 7.27−7.21 (m, 3H), 7.13−7.10 (m, 1H),
6.81−6.80 (m, 2H), 4.16 (s, 2H), 3.90 (s, 3H), 2.68 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 155.6, 148.2,143.3 140.1, 136.7, 134.8, 129.4,
127.6, 122.9, 122.3, 121.8, 119.7, 119.2, 114.4, 111.4, 108.0, 104.1, 55.8,
28.8, 22.5; LRMS (FAB) m/z (relative intensity) 302 (M+, 5), 318
(100), 154 (15), 136 (14); HRMS (FAB) m/z calcd for C20H18N2O1
(M+) 302.1419, found 302.1418.
Data for 3-((1H-indol-3-yl)methyl)-6,7-dimethoxy-2-methylqui-
noline (3pb): yield 279 mg (84%); yellow solid; mp 229−231 °C; 1H
NMR (400 MHz, CDCl3) δ 8.31 (br s, 1H), 7.67 (s, 1H), 7.55 (d, J = 7.9
Hz, 1H), 7.41−7.38 (m, 2H), 7.25−7.21 (m, 1H), 7.14−7.10 (m, 1H),
6.89 (s, 1H), 6.82 (d, J = 1.2 Hz, 1H), 4.21 (s, 2H), 3.99 (s, 3H), 3.93 (s,
3H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.3, 151.9, 149.2,
143.4, 136.7, 134.0, 131.1, 127.6, 122.9, 122.8, 122.4, 119.7, 119.1, 114.2,
111.4, 107.3, 105.1, 56.2, 56.1, 29.0, 23.1; LRMS (FAB) m/z (relative
intensity) 333 (M+ + 1, 100), 281 (35), 149 (100), 147 (81); HRMS
(FAB) m/z calcd for C21H20N2O2 (M + H)+ 333.1603, found 333.1601.
Data for 3-((1H-indol-1-yl)methyl)-2-methylquinoline (3qb): yield
209 mg (77%); pale white solid; mp 151−153 °C; 1H NMR (400 MHz,
CDCl3) δ 8.01 (d, J = 8.4 Hz, 1H), 7.71−7.69 (m, 1H), 7.66−7.62 (m,
1H), 7.55 (d, J = 8.0 Hz, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.33 (s, 1H),
7.25−7.23 (m, 1H), 7.20−7.13 (m, 2H), 7.08−7.07 (m, 1H), 6.63−6.62
(s, 1H), 5.43 (s, 2H), 2.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
156.8, 147.3, 136.4, 133.8, 129.6, 129.4, 128.9, 128.1, 127.6, 127.0, 126.2,
122.2, 121.4, 120.0, 109.6, 102.5, 47.8, 23.2; MS (EI) m/z (relative
intensity) 272 (M+, 100), 156 (25); HRMS (EI) m/z calcd for C19H16N2
(M+) 272.1308, found 272.1316.
Data for 3-((5-fluoro-1H-indol-3-yl)methyl)-2-methylquinoline
1
(3ib): yield 232 mg (80%); red solid; mp 209−211 °C; H NMR
(400 MHz, CDCl3) δ 8.12 (br s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.81 (s,
1H), 7.67−7.61 (m, 2H), 7.46−7.42 (m, 1H), 7.32−7.29 (m, 1H), 7.17
(d, J = 6.9 Hz, 1H), 6.99−6.95 (m, 1H), 6.86 (s, 1H), 4.19 (s, 2H), 2.74
(s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 158.6, 156.6 (d, J = 230.0
Hz), 145.8, 134.2, 133.1 (d, J = 22.0 Hz), 128.4, 127.8, 127.2, 127.1,
126.9, 125.8, 125.5, 112.4 (d, J = 10.0 Hz), 111.9, 111.8, 109.1 (d, J =
26.0 Hz), 103.3 (d, J = 23.0 Hz), 28.2, 23.0; MS (EI) m/z (relative
intensity) 290 (M+, 100), 275 (5), 148 (5); HRMS (EI) m/z calcd for
C19H15FN2 (M+) 290.1219 found 290.1220.
Data for 3-((7-ethyl-1H-indol-3-yl)methyl)-2-methylquinoline
(3jb): yield 228 mg (76%); colorless solid; mp 179−180 °C; 1H NMR
(400 MHz, CDCl3) δ 8.03 (s, 1H), 8.01 (s, 1H), 7.84 (br s, 1H), 7.67−
7.60 (m, 2H), 7.45−7.39 (m, 2H), 7.08−7.07 (m, 2H), 6.81−6.80 (m,
1H), 4.24 (s, 2H), 2.88 (q, J = 7.6 Hz, 2H), 2.76 (s, 3H), 1.38 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.1, 146.7, 135.5, 135.4,
133.1, 128.8, 128.3, 127.5, 127.3, 127.2, 126.9, 125.8, 122.5, 120.9, 120.0,
116.7, 114.2, 29.3, 24.1, 23.4, 13.9; MS (EI) m/z (relative intensity) 301
(M+ + 1, 3), 299 (100), 269 (20), 267 (9), 157 (31), 142 (15), 134 (7);
HRMS (EI) m/z calcd for C21H20N2 (M+) 300.1621, found 300.1628.
Data for 2-methyl-3-((1-methyl-1H-indol-3-yl)methyl)quinoline
1
(3kb): yield 228 mg (80%); yellow solid; mp 142−144 °C; H NMR
General Procedure for the Synthesis of 4a−4d, 5d−5h, 5e′−
5h′, 6a−6d, and 7e. To a stirred solution of cyclic Baylis−Hillman
alcohol (2.0 mmol) in acetonitrile (10.0 mL) were added 2-
methylindole or 2 phenylindole (2.4 mmol, 1.2 equiv) and iodine (0.3
equiv), and the reaction mixture was refluxed until the reaction was
complete, as monitered by TLC. The resulting reaction mixture was
quenched with a saturated solution of sodium thiosulfate and extracted
with ethyl acetate (2.0 × 10.0 mL). The organic layer was separated,
dried over anhydrous magnesium sulfate, and concentrated to give the
crude products. The crude products were purified by passing them
through a short silica gel column (ethyl acetate/hexane).
Data for 2-((2-methyl-1H-indol-3-yl)(2-nitrophenyl)methyl)-
cyclohex-2-enone (4a): yield 626 mg (87%); yellow solid; mp 209−
211 °C; 1H NMR (400 MHz, CDCl3) δ 7.93 (br s, 1H), 7.78 (d, J = 7.8
Hz, 1H), 7.44−7.32 (m, 3H), 7.24 (s, 1H), 7.10−7.03 (m, 2H), 6.91 (t, J
= 7.4 Hz, 1H), 6.59−6.57 (m, 1H), 6.30 (s, 1H), 2.48−2.39 (m, 4H),
2.34 (s, 3H), 2.04−1.94 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 198.0,
149.8, 146.5, 140.4, 137.5, 135.6, 134.0, 132.3, 131.1, 128.3, 127.3, 124.9,
120.7, 119.3, 118.9, 110.8, 108.8, 38.6, 37.2, 26.1, 23.0, 12.1; MS (EI) m/
z (relative intensity) 360 (M+, 100), 343 (19), 270 (22), 247 (12);
HRMS (EI) m/z calcd for C22H20N2O3 (M+) 360.1468, found
360.1481.
Data for 2-((5-fluoro-2-nitrophenyl)(2-methyl-1H-indol-3-yl)-
methyl)cyclohex-2-enone (4b): yield 688 mg (91%); yelow solid; mp
160−162 °C; 1H NMR (400 MHz, CDCl3) δ 8.01 (br s, 1H), 7.88 (dd, J
= 8.6, 5.1 Hz, 1H), 7.23 (s, 1H), 7.08−6.98 (m, 4H), 6.92 (t, J = 7.4 Hz,
1H), 6.61−6.58 (m, 1H), 6.33 (s, 1H), 2.49−2.35 (m, 4H), 2.32 (s, 3H),
2.04−1.94 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 197.9, 164.4 (d, J =
254.0 Hz), 146.9, 145.6, 141.8 (d, J = 7.0 Hz), 140.0, 135.5, 134.1, 128.0,
127.8 (d, J = 10.0 Hz), 120.9, 119.6, 118.6, 118.1 (d, J = 24.0 Hz), 114.2
(d, J = 23.0 Hz) 110.9, 108.0, 38.5, 37.6, 26.1, 22.9, 12.1; MS (EI) m/z
(relative intensity) 378 (M+, 100), 361 (50), 266 (33); HRMS (EI) m/z
calcd for C22H19FN2O3 (M+) 378.1374, found 378.1388.
Data for 2-((5-chloro-2-nitrophenyl)(2-methyl-1H-indol-3-yl)-
methyl)cyclohex-2-enone (4c): yield 693 mg (88%); light yellow
solid; mp 159−161 °C; 1H NMR (400 MHz, CDCl3) δ 7.96 (br s, 1H),
7.76 (d, J = 8.5 Hz, 1H), 7.34−7.30 (m, 2H), 7.24 (s, 1H), 7.08−7.04
(m, 2H), 6.93 (t, J = 7.4 Hz, 1H), 6.61−6.59 (m, 1H), 6.29 (s, 1H),
2.50−2.35 (m, 4H), 2.33 (s, 3H), 2.04−1.98 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 197.8, 148.0, 147.0, 140.0, 139.9, 138.7, 135.5, 134.0,
(400 MHz, DMSO-d6) δ 7.99 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.80 (d, J
= 8.0 Hz, 1H), 7.65−7.61 (m, 1H), 7.51−7.44 (m, 1H), 7.40 (d, J = 8.2
Hz, 1H), 7.16−7.12 (m, 1H), 7.01−6.97 (m, 2H), 4.21 (s, 2H), 3.72 (s,
3H), 2.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.0, 146.6, 137.4,
135.4, 133.2, 128.8, 128.3, 127.8, 127.6, 127.5, 127.2, 125.8, 122.0, 119.2,
119.1, 112.3, 109.4, 32.8, 29.0, 23.4; MS (EI) m/z (relative intensity)
286 (M+, 100), 271 (8), 144 (9); HRMS (EI) m/z calcd for C20H18N2
(M+) 286.1470, found 286.1464.
Data for 3-((1H-indol-3-yl)methyl)-6-chloro-2-methylquinoline
1
(3lb): yield 232 mg (76%); yellow solid; mp 200−202 °C; H NMR
(400 MHz, DMSO-d6) δ 10.94 (br s, 1H), 7.97−7.89 (m, 3H), 7.62 (d, J
= 8.8 Hz, 1H), 7.45 (d, J = 7.7 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.07−
7.05 (m, 2H), 6.95−6.92 (m,1H), 4.22 (s, 2H), 2.66 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 159.4, 145.6, 136.7, 134.3, 134.2, 131.4, 130.0,
129.6, 128.2, 127.4, 126.0, 122.9, 122.5, 119.8, 119.0, 113.4, 111.5, 29.1,
23.5; MS (EI) m/z (relative intensity) 308 (M+, 55), 306 (100), 130 (9);
HRMS (EI) m/z calcd forC19H15ClN2 (M+) 306.0924, found 306.0921.
Data for 3-((1H-indol-3-yl)methyl)-6-bromo-2-methylquinoline
(3mb): yield 262 mg (75%); yellow solid; mp 200−202 °C; 1H NMR
(400 MHz, DMSO-d6) δ 10.93 (br s, 1H), 8.08 (s, 1H), 7.97 (s, 1H),
7.83 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 7.8 Hz,
1H), 7.36 (d, J = 8.0 Hz, 1H), 7.07−7.05 (m, 2H), 6.95−6.92 (m, 1H),
4.21 (s, 2H), 2.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.6, 145.3,
136.7, 134.3, 134.2, 132.2, 130.2, 129.3, 128.7, 127.4, 122.9, 122.6, 119.9,
119.5, 119.0, 113.5, 111.5, 29.2, 23.5; MS (EI) m/z (relative intensity)
350 (M+, 100), 349 (29), 130 (10); HRMS m/z calcd for C19H1579BrN2
(M+) 350.0419, found 350.0421; HRMS (EI) m/z calcd for
C19H1581BrN2 (M+) 352.0398, found 352.0409.
Data for 3-((1H-indol-3-yl)methyl)-6-fluoro-2-methylquinoline
1
(3nb): yield 234 mg (81%); yellow solid; mp 189−191 °C; H NMR
(400 MHz, CDCl3) δ 8.43 (br s, 1H,), 8.01 (dd, J = 9.0, 5.3 Hz, 1H), 7.76
(s, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.41−7.35 (m, 2H), 7.25−7.22 (m,
2H), 7.14−7.10 (m, 1H), 6.83 (s, 1H), 4.23 (s, 2H), 2.75 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 160.1 (d, J = 245.0 Hz), 158.4, 143.7, 136.7,
134.7 (d, J = 5.0 Hz), 134.1, 130.6 (d, J = 9.0 Hz), 128.1 (d, J = 10.0 Hz),
127.4, 122.9, 122.5, 119.8, 119.0, 118.7, 113.4, 111.5, 110.3 (d, J = 21.0
Hz), 29.1, 23.3; MS (EI) m/z (relative intensity) 290 (M+, 100), 275
(7), 130 (9); HRMS (EI) m/z calcd for C19H15FN2 (M+) 290.1219,
found 290.1218.
8461
dx.doi.org/10.1021/jo301313m | J. Org. Chem. 2012, 77, 8451−8464

The Journal of Organic Chemistry
Article
130.9, 128.0, 127.5, 126.5, 121.0, 119.7, 118.6, 110.8, 108.1, 38.5, 37.3,
26.2, 22.9, 12.2; MS (EI) m/z (relative intensity) 394 (M+, 100), 377
(65), 299 (34), 282 (41); HRMS (EI) m/z calcd for C22H1935ClN2O3
(M+) 394.1079, found 394.1085; HRMS (EI) m/z calcd for C22H1937Cl
N2O3(M+) 396.1049, found 396.1070.
127.0 (d, J = 10.0 Hz), 126.6, 126.1, 122.2, 119.1 (d, J = 21.0 Hz), 117.7,
117.5, 115.5 (d, J = 23.0 Hz), 115.3, 109.4, 37.5, 36.5, 32.6, 28.8; MS
(EI) m/z (relative intensity) 364 (M+, 100); HRMS (EI) m/z calcd for
C21H17FN2O3 (M+) 364.1218, found 364.1222.
Data for (E)-3-(2-methyl-1H-indol-3-yl)-2-(2-nitrobenzylidene)-
cyclopentanone (6c): yield 602 mg (87%); dark red solid; mp 206−
207 °C; 1H NMR (400 MHz, CDCl3) δ 7.89−7.88 (m, 1H), 7.68−7.66
(m, 1H), 7.42 (br s, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.07- 7.01 (m, 3H),
7.00−6.89 (m, 3H), 4.37−4.33 (m, 1H), 2.67−2.64 (m, 1H), 2.59−2.52
(m, 1H), 2.39−2.37 (m, 1H), 2.36−2.17 (m, 1H), 2.16 (s, 3H); 13C
NMR (100 MHz, CDCl3 and DMSO-d6) δ 206.8, 146.2, 140.8, 135.0,
131.3, 131.1, 130.1, 130.0, 129.6, 128.1, 126.0, 123.2, 119.8, 117.9, 117.6,
109.9, 109.9, 37.4, 37.3, 28.3, 11.3; MS (EI) m/z (relative intensity) 346
(M+, 100), 285 (15); HRMS (EI) m/z calcd for C21H18N2O3 (M+)
346.1312, found 346.1326.
Data for (E)-2-(5-fluoro-2-nitrobenzylidene)-3-(2-methyl-1H-
indol-3-yl)cyclopentanone (6d): yield 662 mg (91%); red solid; mp
185−187 °C; 1H NMR (400 MHz, CDCl3) δ 7.86−7.85 (m, 1H), 7.64
(dd, J = 9.0, 5.1 Hz, 1H), 7.49 (br s, 1H), 7.13 (d, J = 7.9 Hz, 1H), 7.03−
6.96 (m, 2H), 6.86 (t, J = 7.3 Hz, 1H), 6.71−6.62 (m, 2H), 4.34 (t, J =
7.3 Hz, 1H), 2.70−2.68 (m, 1H), 2.67−2.55 (m, 1H), 2.40−2.38 (m,
1H), 2.28 (s, 3H), 2.26−2.18 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
206.7, 163.5 (d, J = 255.0 Hz), 142.9, 141.6, 135.3, 134.1 (d, J = 10.0
Hz), 131.2, 129.9, 126.4, 126.3 (d, J = 4.0 Hz), 121.5, 119.5, 118.7, 117.3
(d, J = 24.0 Hz), 115.1 (d, J = 23.0 Hz), 111.1, 110.0, 38.1, 37.9, 28.5,
11.8; MS (EI) m/z (relative intensity) 364 (M+, 100), 318 (15); HRMS
(EI) m/z calcd for C21H17 FN2O3 (M+) 364.1218, found 364.1233.
Data for 2-((2-nitrophenyl)(2-phenyl-1H-indol-3-yl)methyl)-
cyclopent-2-enone (7e): yield 718 mg (88%); yellow solid; mp 231−
233 °C; 1H NMR (400 MHz, CDCl3) δ 8.17 (br s, 1H), 7.80 (d, J = 7.8
Hz, 1H), 7.48−7.43 (m, 4H), 7.42−7.33 (m, 5H), 7.23 (d, J = 8.2 Hz,
1H), 7.16 (t, J = 7.5 Hz, 1H), 7.09 (s, 1H), 6.99 (t, J = 7.5 Hz, 1H), 6.21
(s, 1H), 2.53−2.46 (m, 1H), 2.43−2.37 (m, 2H), 2.29−2.27 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 207.2, 159.0, 149.5, 147.1, 137.3, 136.8,
Data for 2-((5-bromo-2-nitrophenyl)(2-methyl-1H-indol-3-yl)-
methyl)cyclohex-2-enone (4d): yield 683 mg (78%); yellow solid;
mp 180−182 °C; 1H NMR (400 MHz, CDCl3) δ 7.96 (br s, 1H), 7.67
(d, J = 8.4 Hz, 1H), 7.50−7.47 (m, 2H), 7.24 (s, 1H), 7.08−7.05 (m,
2H), 6.94 (t, J = 7.5 Hz, 1H), 6.61−6.59 (m, 1H), 6.29 (s, 1H), 2.50−
2.35 (m, 4H), 2.32 (s, 3H), 2.04−1.98 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 197.9, 148.5, 147.2, 139.9, 139.8, 135.5, 134.0, 133.8, 130.5,
127.9, 127.2, 126.5, 120.9, 119.6, 118.5, 110.9, 108.0, 38.5, 37.3, 26.1,
22.9, 12.1; MS (EI) m/z (relative intensity) 439 (M+ +1, 80), 438 (M+,
100), 421 (73), 345(34), 326(41), 218(30), 146(41); HRMS (EI) m/z
calcd for C22H1979BrN2O3 (M+) 438.0574 found 438.056; HRMS (EI)
m/z calcd for C22H1981BrN2O3 (M+) 440.0553, found 440. 0562.
Data for (E)-2-(5-bromo-2-nitrobenzylidene)-3-(2-methyl-1H-
indol-3-yl)cyclohexanone (5d): yield 96 mg (11%); red solid; mp
205−207 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (br s, 1H), 7.54−7.52
(m, 2H), 7.18−7.11 (m, 3H), 7.03 (t, J = 7.5 Hz, 1H), 6.98 (s, 1H), 6.93
(t, J = 7.4 Hz, 1H), 4.13 (t, J = 6.0 Hz, 1H), 2.75−2.71 (m, 2H), 2.15 (s,
3H), 2.08−1.90 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 201.1, 145.2,
140.8, 135.0, 134.6, 134.5, 132.8, 131.0, 130.6, 127.4, 126.9, 125.3, 121.5,
119.5, 118.5, 114.6, 110.2, 40.4, 35.9, 31.9, 21.6, 12.5; MS (EI) m/z
+
(relative intensity) 440 (M + 2, 93), 438 (M+, 100), 394 (47), 349
(15); HRMS (EI) m/z calcd for C22H1979BrN2O3 (M+) 438.0574, found
438.0566; HRMS (EI) m/z calcd for C22H1981BrN2O3 (M+) 440.0553,
found 440.0551.
Data for (E)-2-(2-nitrobenzylidene)-3-(2-phenyl-1H-indol-3-yl)-
cyclohexanone (5e): yield 658 mg (78%); yellow solid; mp 219−221
°C; 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.72 (br s, 1H), 7.69 (d,
J = 7.5 Hz, 1H), 7.42−7.31 (m, 4H), 7.21−7.09 (m, 5H), 7.03−6.99 (m,
2H), 6.60 (d, J = 7.6 Hz, 1H), 4.37 (t, J = 6.0 Hz, 1H), 2.74−2.72 (m,
2H), 2.16−2.13 (m, 3H), 1.97−1.93 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 201.3, 146.1, 139.7, 136.7, 136.0, 134.0, 132.6, 132.5, 132.2,
129.6, 128.8, 128.2, 128.1, 128.0, 126.9, 124.0, 122.5, 120.5, 119.8, 115.7,
110.8, 40.2, 35.8, 32.6, 21.6; MS (EI) m/z (relative intensity) 422 (M+,
100), 375 (33), 182 (30); HRMS (EI) m/z calcd for C27H22N2O3 (M+)
422.1625, found 422.1628.
Data for (Z)-2-(2-nitrobenzylidene)-3-(2-phenyl-1H-indol-3-yl)-
cyclohexanone (5e′): yield 109 mg (13%); yellow solid; mp 199−
200 °C; 1H NMR (400 MHz, CDCl3) δ 8.17 (br s, 1H), 8.04 (d, J = 8.0
Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.63−7.61 (m, 2H), 7.54−7.41 (m,
5H), 7.34 (t, J = 7.6 Hz, 1H), 7.24−7.13 (m, 3H), 6.71 (d, J = 1.8 Hz,
1H), 4.24−4.21 (m, 1H), 2.66−2.60 (m, 3H), 2.14−2.04 (m, 2H),
1.86−1.84 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 203.1, 147.5, 142.4,
136.8, 136.7, 134.9, 133.1, 132.7, 132.5, 130.5, 129.3, 128.6, 128.5, 127.9,
127.0, 124.5, 122.4, 121.2, 111.6, 119.8, 112.4, 43.5, 43.0, 32.0, 24.5; MS
(EI) m/z (relative intensity) 422 (M+, 100), 375 (33), 182 (30); HRMS
(EI) m/z calcd for C27H22N2O3 (M+) 422.1625, found 422.1628.
Data for (E)-3-(1H-indol-3-yl)-2-(2-nitrobenzylidene)-
cyclopentanone (6a): yield 538 mg (81%); yellow solid; mp 151−
153 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (br s, 1H), 7.89−7.87 (m,
1H), 7.84 (d, J = 1.8 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.36−7.31 (m,
2H), 7.29−7.27 (m, 2H), 7.22−7.18 (m, 1H), 7.11 (t, J = 7.4 Hz, 1H),
6.82 (d, J = 1.4 Hz, 1H), 4.54−4.56 (m, 1H), 2.51−2.38 (m, 2H), 2.37−
2.29 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 207.4, 148.5, 142.1,
136.9, 133.0, 131.0, 130.7, 129.5, 129.2, 125.9, 124.5, 122.6, 122.0, 119.7,
119.1, 117.1, 111.5, 37.4, 35.9, 28.5; MS (EI) m/z (relative intensity)
332 (M+, 100); HRMS (EI) m/z calcd for C20H16N2O3 (M+) 332.1155,
found 332.1157.
136.1, 132.7, 132.7, 131.1, 129.0, 128.8, 128.5, 128.4, 127.7, 125.0, 122.2,
120.1, 119.9, 111.4, 109.3, 35.6, 34.7, 26.5; MS (EI) m/z (relative
intensity) 408 (M+, 80), 310 (50), 281(34), 207 (100); HRMS (EI) m/z
calcd for C26H20N2O3 (M+) 408.1468, found 408.1483.
General Procedure for the Synthesis of 8a−8h. To a stirred
solution of C-alkylated cyclic Baylis−Hillman adducts containing
indoles (1.0 mmol) in acetic acid (5.0 mL) was added powdered Fe
(6.0 mmol, 6.0 equiv), and the reaction mixture was then refluxed for 2
h. The mixture was cooled to room temperature, the acetic acid was
removed under reduced pressure, and EtOAc (10.0 mL) was added. The
resulting mixture was stirred for 2 min, and iron impurities were
removed by filtration. The insoluble iron residue was washed with
EtOAc (10.0 mL). The filtrate and washings were combined and dried
over anhydrous MgSO4. The solvent was removed under reduced
pressure, and all of the crude products were purified by passing them
through a short silica gel column (ethyl acetate/hexane).
Data for 1-(2-Methyl-1H-indol-3-yl)-1,2,3,4-tetrahydroacridine
1
(8a): yield 249 mg (80%); white solid; mp 244−246 °C; H NMR
(400 MHz, DMSO-d6) δ 10.83 (br s, 1H), 7.88 (d, J = 8.3 Hz, 1H),
7.61−7.57 (m, 3H), 7.35 (t, J = 7.3 Hz, 1H), 7.25 (d, J = 7.9 Hz, 1H),
6.89 (d, J = 7.4 Hz, 1H), 6.79 (d, J = 7.7 Hz, 1H), 6.67 (t, J = 7.3 Hz, 1H),
4.49 (t, J = 7.4 Hz, 1H), 3.20−3.21 (m, 2H), 2.34 (s, 3H), 2.13−1.97 (m,
4H); 13C NMR (100 MHz, DMSO-d6) δ 159.8, 145.9, 135.6, 134.7,
134.4, 132.3, 128.5, 127.7, 127.3, 126.9, 126.5, 125.3, 119.7, 118.2, 118.0,
113.5, 110.6, 35.8, 33.7, 30.8, 22.4, 11.6; MS (EI) m/z (relative
intensity) 312 (M+, 100), 181 (54); HRMS (EI) m/z calcd for C22H20N2
(M+) 312.1621, found 312.1632.
Data for 7-fluoro-1-(2-methyl-1H-indol-3-yl)-1,2,3,4-tetrahydroa-
cridine (8b): yield 274 mg (83%); pale gray solid; mp 245−247 °C; 1H
NMR (400 MHz, DMSO-d6) δ 10.85 (br s, 1H), 7.96−7.92 (m, 1H),
7.62 (s, 1H), 7.51−7.47 (m, 2H), 7.25 (d, J = 8.0 Hz, 1H), 6.90 (t, J = 7.4
Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.69 (t, J = 7.4 Hz, 1H), 4.49 (t, J = 7.6
Hz, 1H), 3.20−3.21 (m, 2H), 2.34 (s, 3H), 2.14−1.98 (m, 4H); 13C
NMR (100 MHz, DMSO-d6) δ 159.0 (d, J = 242.0 Hz), 158.3, 143.1,
135.6, 135.4, 134.4 (d, J = 20.0 Hz), 132.4, 130.4 (d, J = 10.0 Hz), 127.4
(d, J = 10.0 Hz), 126.4, 119.8, 118.5 (d, J = 26.0 Hz), 118.2, 118.0, 113.3,
Data for (E)-2-(5-fluoro-2-nitrobenzylidene)-3-(1-methyl-1H-
indol-3-yl)cyclopentanone (6b): yield 575 mg (79%); yellow solid;
mp 150−152 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 9.0, 5.1
Hz, 1H), 7.79 (d, J = 2.4 Hz, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.19−7.18
(m, 2H), 7.06−7.02 (m, 1H), 7.83 (dd, J = 8.7, 2.7 Hz, 1H), 6.86−6.81
(m, 1H), 6.65 (s, 1H), 4.48−4.47 (m, 1H), 3.62 (s, 3H), 2.55−2.42 (m,
2H), 2.41−2.27 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 206.9, 164.1
(d, J = 256.0 Hz), 144.1, 143.1, 137.4, 134.5 (d, J = 10.0 Hz), 129.0,
8462
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110.6, 110.1 (d, J = 22 Hz), 35.8, 33.5, 30.7, 22.4, 11.6; MS (EI) m/z
(relative intensity) 330 (M+, 100), 199 (40); HRMS (EI) m/z calcd for
C22H19FN2 (M+) 330.1527, found 330.1528.
Data for 7-chloro-1-(2-methyl-1H-indol-3-yl)-1,2,3,4-tetrahy-
droacridine (8c): yield 280 mg (81%); white solid. mp 246−247 °C;
1H NMR (400 MHz, DMSO-d6) δ 10.86 (br s, 1H), 7.90 (d, J = 8.9 Hz,
Hz, 1H), 4.59 (dd, J = 11.0, 4.7 Hz, 1H), 3.27−3.17 (m, 2H), 2.28−2.25
(m, 1H), 2.16−2.14 (m, 2H), 1.98−1.95 (m, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 159.5, 144.3, 136.6, 136.0, 135.5, 133.9, 132.8, 131.6,
129.8, 129.3, 128.8, 128.4, 128.1, 127.8, 125.9, 121.2, 119.7, 118.5, 118.2,
114.0, 111.5, 36.5, 33.6, 30.7, 22.6; MS (EI) m/z (relative intensity) 454
(M+ + 2, 100), 452 (M+, 90), 261 (9); HRMS (EI) m/z calcd for
C27H2179BrN2 (M+) 452.0883, found 452.0878; HRMS (EI) m/z calcd
for C27H2181BrN2 (M+) 454.0862, found 454.0870.
General Procedure for the Synthesis of 8i−8m. To a stirred
solution of C-alkylated cyclic Baylis−Hillman adducts containing
indoles (1.0 mmol) in acetic acid (5.0 mL) was added powdered Fe
(6.0 mmol, 6.0 equiv), and the reaction mixture was heated at 80 °C for 2
h. The mixture was cooled to room temperature, the acetic acid was
removed under reduced pressure, and EtOAc (10.0 mL) was added. The
resulting mixture was stirred for 2 min, and iron impurities were
removed by filtration. The insoluble iron residue was washed with
EtOAc (10.0 mL). The filtrate and washings were combined and dried
over anhydrous MgSO4. The solvent was removed under reduced
pressure, and all of the crude products were purified by passing them
through a short silica gel column (ethyl acetate/hexane).
Data for 1-(1H-indol-3-yl)-2,3-dihydro-1H-cyclopenta[b]-
quinoline (8i): yield 196 mg (69%); pale brown solid; mp 235−237
°C; 1H NMR (400 MHz, CDCl3) δ 8.36 (br s, 1H), 8.15 (d, J = 8.4 Hz,
1H), 7.82 (s, 1H), 7.67−7.63 (m, 2H), 7.46−7.41 (m, 3H), 7.23−7.19
(m, 1H), 7.08−7.04 (m, 1H), 7.00 (d, J = 2.2 Hz, 1H), 4.81 (t, J = 8.3 Hz,
1H), 3.39−3.26 (m, 2H), 2.76−2.68 (m, 1H), 2.47−2.39 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 167.3, 146.8, 139.2, 137.0, 132.1, 129.2,
128.0, 128.0, 127.7, 126.6, 126.1, 122.4, 121.9, 119.7, 119.5, 118.2, 111.6,
40.6, 33.7, 33.1; MS (EI) m/z (relative intensity) 284 (M+, 100), HRMS
(EI) m/z calcd for C20H16N2 (M+), 284.1308, found 284.1300.
Data for 7-fluoro-1-(1-methyl-1H-indol-3-yl)-2,3-dihydro-1H-
cyclopenta[b]quinoline (8j): yield 208 mg (66%); yellow solid; mp
239−241 °C; 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 9.0, 5.1 Hz,
1H), 7.74 (br s, 1H), 7.43−7.34 (m, 4H), 7.27 (s, 1H), 7.06 (t, J = 7.4
Hz, 1H), 6.85 (s, 1H), 4.78 (t, J = 8.3 Hz, 1H), 3.76 (s, 3H), 3.35−3.24
(m, 2H), 2.74−2.68 (m, 1H), 2.43−2.38 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 166.8, 160.2 (d, J = 245.0 Hz), 144.1, 140.2, 137.7, 131.1 (d, J
= 5.0 Hz), 130.4 (d, J = 9.0 Hz), 128.4 (d, J = 10.0 Hz), 126.9, 126.5,
122.1, 119.5, 119.2, 118.9 (d, J = 26.0 Hz), 116.6, 111.1 (d, J = 22.0 Hz),
109.7, 40.6, 33.6, 33.3, 32.9. MS (EI) m/z (relative intensity) 316 (M+,
100); HRMS (EI) m/z calcd for C21H17FN2 (M+) 316.1370, found
316.1370.
1H), 7.81 (s, 1H), 7.64 (s, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.25 (d, J = 7.9
Hz, 1H), 6.90 (t, J = 7.3 Hz, 1H), 6.80 (d, J = 7.6 Hz, 1H), 6.68 (t, J = 7.3
Hz, 1H), 4.50 (t, J = 7.1 Hz, 1H), 3.20−3.22 (m, 2H), 2.33 (s, 3H),
2.09−1.98 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ 159.5, 144.0,
135.6, 135.5, 134.2, 132.4, 129.7, 129.6, 129.1, 127.6, 126.4, 125.9, 119.7,
118.1, 118.0, 113.2, 110.6, 35.8, 33.5, 30.7, 22.2, 11.6; MS (EI) m/z
(relative intensity) 346 (M+, 100), 215 (63); HRMS (EI) m/z calcd for
C22H1935ClN2 (M+) 346.1231, found 346.1240; HRMS (EI) m/z calcd
for C22H1937ClN2 (M+) 348.1202, found 348.1219.
Data for 7-bromo-1-(2-methyl-1H-indol-3-yl)-1,2,3,4-tetrahy-
droacridine (8d): yield 319 mg (82%); light yellow solid; mp 259−
261 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.86 (br s, 1H), 7.95 (d, J =
1.8 Hz, 1H), 7.82 (d, J = 8.9 Hz, 1H), 7.70−7.68 (m, 1H), 7.61 (s, 1H),
7.25 (d, J = 8.0 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 7.8 Hz, 1H),
6.68 (t, J = 7.3 Hz, 1H), 4.50 (t, J = 7.4 Hz, 1H), 3.21−3.20 (m, 2H), 2.33
(s, 3H), 2.13−1.98 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ 159.8,
144.4, 135.7, 135.6, 134.1, 132.5, 131.6, 130.0, 129.3, 128.3, 126.5, 119.8,
118.3, 118.2, 118.1, 113.4, 110.7, 35.9, 33.7, 30.7, 22.3, 11.6; MS (EI) m/
z (relative intensity) 392 (M+ + 2, 100), 390 (M+, 77); HRMS (EI) m/z
calcd for C22H1979BrN2 (M+) 390.0726, found 390.0725; HRMS (EI)
m/z calcd for C22H1981BrN2 (M+) 392.0706, found 392.0714.
Data for 1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-tetrahydroacridine
1
(8e): yield 310 mg (83%); white solid; mp 272−273 °C; H NMR
(400 MHz, DMSO-d6) δ 11.34 (br s, 1H), 7.89 (d, J = 8.4 Hz, 1H),
7.67−7.57 (m, 5H), 7.54−7.50 (m, 2H), 7.43−7.32 (m, 2H), 7.01 (t, J =
7.4 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.73 (t, J = 7.4 Hz, 1H), 4.61 (dd, J
= 11.2, 4.7 Hz, 1H), 3.28−3.24 (m, 2H), 2.32−2.29 (m, 1H), 2.17−2.14
(m, 2H), 1.98−1.96 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 158.6,
145.9, 136.6, 135.9, 134.5, 134.3, 132.8, 128.8, 128.6, 128.3, 127.8, 127.7,
127.3, 126.8, 126.0, 125.3, 121.2, 119.8, 118.5, 114.3, 111.5, 36.5, 33.6,
30.8, 22.8; MS (EI) m/z (relative intensity) 374 (M+, 100), 181 (8);
HRMS (EI) m/z calcd for C27H22N2 (M+) 374.1778, found 374.1783.
Data for 7-fluoro-1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-tetrahydroa-
1
cridine (8f): yield 333 mg (85%); white solid; mp 265−266 °C; H
NMR (400 MHz, DMSO-d6) δ 11.33 (br s, 1H), 7.94 (dd, J = 9.9, 5.3
Hz, 1H), 7.68−7.64 (m, 3H), 7.54−7.47 (m, 4H), 7.43−7.37 (m, 2H),
7.01 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.74 (t, J = 7.4 Hz, 1H),
4.59 (dd, J = 11.2, 4.7 Hz, 1H), 3.27−3.18 (m, 2H), 2.31−2.28 (m, 1H),
2.16−2.14 (m, 2H), 1.98−1.94 (m, 1H); 13C NMR (100 MHz, DMSO-
d6) δ 159.2 (d, J = 245.0 Hz), 158.1, 143.1, 136.6, 135.9, 135.2, 134.1 (d,
J = 5.0 Hz), 132.8, 130.4 (d, J = 9.0 Hz), 128.8, 128.3, 127.7, 127.4 (d, J =
10.0 Hz), 126.0, 121.2, 119.7, 118.7, 118.5, 118.4, 114.1, 111.5, 110.2 (d,
J = 22 Hz), 36.5, 33.5, 30.8, 22.7; MS (EI) m/z (relative intensity) 392
(M+, 100), 199 (8); HRMS (EI) m/z calcd for C27H21FN2 (M+)
392.1683, found 392.1690.
Data for 1-(2-methyl-1H-indol-3-yl)-2,3-dihydro-1H-cyclopenta-
[b]quinoline (8k): yield 223 mg (75%); brown solid; mp 232−233 °C;
1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 7.95 (br s, 1H),
7.65−7.58 (m, 3H), 7.40 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H),
7.07 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.84 (t, J = 7.4 Hz, 1H),
4.74 (t, J = 9.0 Hz, 1H), 3.39−3.30 (m, 2H), 2.62−2.57 (m, 1H), 2.48−
2.45 (m, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6,
147.8, 138.6, 135.8, 132.0, 131.2, 128.7, 128.6, 128.0, 127.7, 127.1, 125.7,
121.1, 119.4, 119.2, 112.5, 110.6, 40.4, 34.2, 32.7, 12.3; MS (EI) m/z
(relative intensity) 298 (M+, 100), 282 (78); HRMS (EI) m/z calcd for
C21H18N2 (M+) 298.1465, found 298.1467.
Data for 7-chloro-1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-tetrahydroa-
1
cridine (8g): yield 342 mg (84%); yellow solid; mp 281−282 °C; H
NMR (400 MHz, DMSO-d6) δ 11.34 (br s, 1H), 7.89 (d, J = 9.0 Hz,
1H), 7.81 (d, J = 1.7 Hz, 1H), 7.68−7.60 (m, 3H), 7.60−7.57 (m, 1H),
7.54−7.50 (m, 2H), 7.43−7.37 (m, 2H), 7.01 (t, J = 7.5 Hz, 1H), 6.86
(d, J = 7.9 Hz, 1H), 6.74 (t, J = 7.4 Hz, 1H), 4.59 (dd, J = 11.9, 4.7 Hz,
1H), 3.28−3.23 (m, 2H), 2.31−2.28 (m, 1H), 2.16−2.14 (m, 2H),
1.98−1.94 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 159.3, 144.2,
136.6, 136.0, 135.5, 134.0, 132.8, 129.8, 129.7, 129.1, 128.8, 128.3, 127.8,
127.6, 126.0, 125.9, 121.2, 119.7, 118.5, 114.0, 111.5, 36.5, 33.5, 30.7,
22.6; MS (EI) m/z (relative intensity) 408 (M+, 100), 214 (7); HRMS
(EI) m/z calcd for C27H2135ClN2 (M+) 408.1388, found 408.1389;
HRMS (EI) m/z calcd for C27H2137ClN2 (M+) 410.1358, found
410.1375.
Data for 7-bromo-1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-tetrahy-
droacridine (8h): yield 375 mg (83%); yellow solid; mp 269−270 °C;
1H NMR (400 MHz, DMSO-d6) δ 11.33 (br s, 1H), 7.97 (s, 1H), 7.82
(d, J = 8.9 Hz, 1H), 7.70−7.64 (m, 4H), 7.54−7.50 (m, 2H), 7.43−7.37
(m, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.74 (t, J = 7.4
Data for 7-fluoro-1-(2-methyl-1H-indol-3-yl)-2,3-dihydro-1H-
cyclopenta[b]quinoline (8l): yield 243 mg (77%); pale yellow solid;
mp 247−249 °C; 1H NMR (400 MHz, CDCl3) δ 8.07 (dd, J = 9.1, 5.3
Hz, 1H), 7.96 (br s, 1H), 7.55 (s, 1H), 7.40−7.33 (m, 1H), 7.21 (d, J =
8.0 Hz, 1H), 7.21−7.18 (m, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.90 (d, J = 7.6
Hz, 1H), 6.85 (t, J = 7.3 Hz, 1H), 4.73 (t, J = 9.3 Hz, 1H), 3.36−3.29 (m,
2H), 2.63−2.58 (m, 1H), 2.49−2.46 (m, 1H), 2.44 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 166.8, 159.1 (d, J = 242.0 Hz), 144.2, 139.6,
135.7, 132.6, 130.6 (d, J = 9.0 Hz), 129.4 (d, J = 5.0 Hz), 127.8 (d, J =
11.0 Hz), 126.4, 119.8, 118.1, 118.0 (d, J = 4.0 Hz), 117.8, 111.0, 110.8,
110.8 (d, J = 11.0 Hz), 33.2, 32.0, 11.7, 11.6; MS (EI) m/z (relative
intensity) 316 (M+, 100), 301 (26); HRMS (EI) m/z calcd for
C21H17FN2 (M+) 316.1370, found 316.1375.
Data for 1-(2-phenyl-1H-indol-3-yl)-2,3-dihydro-1H-cyclopenta-
[b]quinoline (8m): yield 190 mg (53%); pale brown solid; mp 267−269
°C; 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 8.09 (d, J = 8.4 Hz,
1H), 7.64−7.58 (m, 5H), 7.52−7.48 (m, 2H), 7.43−7.38 (m, 3H),
8463
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7.16−7.12 (m, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.85 (t, J = 7.3 Hz, 1H),
4.95−4.90 (m, 1H), 3.42−3.36 (m, 1H), 3.36−3.27 (m, 1H), 2.69−2.62
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 167.4, 147.8, 138.7, 136.7,
136.6, 133.1, 131.1, 129.2, 128.9, 128.7, 128.6, 128.4, 128.0, 127.7, 126.9,
125.7, 122.3, 120.9, 119.6, 113.5, 111.3, 40.7, 34.1, 32.8; MS (EI) m/z
(relative intensity) 360 (M+, 100); HRMS (EI) m/z calcd for C26H20N2
(M+) 360.1621, found 360.1626.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Crystallographic data of compound 4a, 5e, 5e' and 8a and 1H and
13C NMR copies of all the compounds are available in the
Supporting Information. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: cheyaocf@ntnu.edu.tw.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support for this work by the National Science Council
of the Republic of China (Grant NSC 100-2113-M-003-008-
MY3) and National Taiwan Normal University (Grants
99T3030-2, 99-D and 100-D-06) is gratefully acknowledged.
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