Synthesis of 5-iodopyrrolo[1,2- a ]quinolines and indolo[1,2- a ]quinolines via iodine-mediated electrophilic and regioselective 6- endo - Dig ring closure

Article abstract of DOI:10.1021/jo200638k

The endo-cyclic ring closure of 1-(2-(substituted ethynyl)phenyl)-1H- pyrroles 3-t and 1-(2-(substituted ethynyl)phenyl)-H-indole 4-o mediated by Lewis acid (I₂) under mild conditions afforded substituted 5-iodopyrrolo[1,2-a]quinolines 5-t and 5-iodoindolo[1,2-a]quinolines 6-o in good to excellent yields. The reaction shows selective C - C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized product. Iodo derivatives of pyrrolo- and indoloquinolines allow functional group diversification on the quinoline nucleus, which proves to be highly advantageous for structural and biological activity assessments.

Full text of DOI:10.1021/jo200638k

ARTICLE
pubs.acs.org/joc
Synthesis of 5-Iodopyrrolo[1,2-a]quinolines and
Indolo[1,2-a]quinolines via Iodine-Mediated Electrophilic and
Regioselective 6-endo-dig Ring Closure
Akhilesh Kumar Verma,* Satya Prakash Shukla, Jaspal Singh, and Vineeta Rustagi
Synthetic Organic Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India
S Supporting Information
b
ABSTRACT: The endo-cyclic ring closure of 1-(2-(substituted
ethynyl)phenyl)-1H-pyrroles 3aÀtand 1-(2-(substituted ethynyl)-
phenyl)-H-indole 4aÀo mediated by Lewis acid (I2)
under mild conditions afforded substituted 5-iodopyrrolo[1,2-a]-
quinolines 5aÀt and 5-iodoindolo[1,2-a]quinolines 6aÀo in good
to excellent yields. The reaction shows selective CÀC bond
formation on the more electrophilic alkynyl carbon, resulting in
the regioselective 6-endo-dig-cyclized product. Iodo derivatives of
pyrrolo- and indoloquinolines allow functional group diversification on the quinoline nucleus, which proves to be highly advantageous for
structural and biological activity assessments.
’ INTRODUCTION
pyrrazoles,10 pyranoquinolines, pyranoquinolinones, and isocu-
marins,11 indoles, quinolines, and quinolinones,12 benzo[b]-
thiophenes,13 pyrroles,14 naphthalenes,15 isochromenes,16 phos-
phaisocoumarins,17 and other heterocycles18 by electrophilic
cyclization of the alkynes using Lewis acids such as ICl and I2,
an alternate method for the preparation of iodo derivatives of
pyrrolo- and indoloquinolines has been reported. This method
allows functional group variation on the quinoline nucleus, which
subsequently proves highly desirable for structural and biological
activity assessments. In continuation of our efforts to adapt
heterocyclic chemistry,11,19 we herein report an electrophilic cy-
clization reaction employing the use of I2, which is more eco-
nomical and convenient to handle than other reported media.
Furthermore, this cyclization method leads to the synthesis of
halogen-containing quinoline derivatives which thereafter can
be elaborated using various palladium- and copper-catalyzed
coupling reactions, such as the SuzukiÀMiyaura, Sonogashira,
Heck, and Ullmann reactions.
Numerous natural products and biologically active molecules
are comprised of nitrogen-containing subunits. Synthesis of
hetrocycles has been a prominent research objective for over a
century, and a variety of well-established methods are available in
the literature. Development of new approaches for their synth-
eses, employing efficient and economical routes, is currently a
popular research area. Among different N-heterocycles, indole
and pyrrole rings are known to exert biological activity in many
active pharmaceutical ingredients.1 Pyrrolo[1,2-a]quinolines and
indolo[1,2-a]quinolines are such molecules which have unique
nitrogen-containing tricyclic and tetracyclic stuctures derived
from pyrrole and indole, and their reduced and oxidized forms
occur widely among natural products.2 These polycyclic com-
pounds are also identified as rigid molecular platforms critical to
advances in various areas of chemical research such as hostÀ
guest chemistry,3 liquid crystal chemistry,4 and even biochemical
studies of synthetic peptides.5
Synthesis of pyrrolo- and indoloquinolines is one of the least
explored areas. Reported methods6 for the synthesis of pyrrolo-
and indoloquinolines are limited and multistep and suffer from
availability of starting materials. Few of the recently reported
methods include Lautens’s protocol, which employed the synth-
esis of pyrrolo- and indolo[1,2-a]quinolines from gem-dibromo-
vinyl substrates by the sequential SuzukiÀMiyuara coupling/
direct arylation using S-Phos ligand under palladium catalysis at
100 °C (Scheme 1A).7 Furthermore, in another report, Pd(OAc)2
along with norbornene ligand and PPh3 as a coligand in toluene
at 110 °C was used for the synthesis of fused heterocyclic
scaffolds (Scheme 1B).8
In our preceding report for the synthesis of indolo[2,1-a]-
isoquinolines 10,19a we came up with an interesting outcome
(Scheme 2). In the report we described that the initial attempt
was to synthesize indolo[1,2-a]quinolines 11 starting from
indole 7 and o-haloalkyne 8 via the anticipated route 1, i.e.,
N-arylation followed by intramolecular electrophilic cyclization
without isolating intermediate 4. The reaction surprisingly pro-
ceeded via route 2 and afforded the indolo[2,1-a]isoquinolines
10, regioisomers of 11, via the formation of hydroaminated inter-
mediate 9 (Scheme 2)
However, in keeping with the recently reported synthesis of
Received: March 26, 2011
Published: May 27, 2011
halo derivatives of numerous heterocycles such as benzoxepine,9
r
2011 American Chemical Society
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Scheme 1. Previous Approaches To Synthesize Pyrrolo/Indoloquinolines
Scheme 2. Previous Effort of Our Laboratory
Scheme 3. Designed Pathway for the Synthesis of Pyrrolo/
Indoloquinolines
Scheme 4
From our previous experience, we concluded that intermedi-
ates 3 and 4 (Scheme 3) are crucial for the formation of pyrrolo-
and indolo[1,2-a]quinolines. We herein designed an alternate
two-step process to obtain the desired pyrrolo/indolo[1,2-a]-
quinolines via intermediates 3 and 4 (Scheme 3).
complex PdCl2(PPh3)2 (5 mol %) in the presence of CuI (1 mol %)
as the cocatalyst using Et3N (2 equiv) as the base in CH3CN for
1À2 h at 60 °C under an inert atmosphere (Scheme 4). Though
all the terminal alkynes coupled efficiently, it was found that
the alkynes with electron-donating groups such as Me, OMe, Et,
t-Bu, n-Bu, and NMe2 coupled efficiently and afforded the
coupling products in 74À92% yields.
’ RESULTS AND DISCUSSION
With an effective protocol for N-arylations of pyrrole and
Sonogashira coupling in hand, we then aimed to identify the op-
timal reaction conditions for electrophilic iodocyclization reac-
tion. Several electrophiles and bases were examined along with
variation in time and temperature for the electrophilic cyclization
of 1-(2-(phenylethynyl)phenyl)-1H-pyrrole (3a). Interesting
observations emerged from the data in Table 1. We first reacted
To probe the viability of the envisioned protocol (Scheme 3),
we first carried out copper-catalyzed direct arylations of pyrrole/
indole with o-dihalobenzenes per the protocol developed for
different N-hetrocycles in our laboratory.19e,f The arylated sub-
strates 1 and 2 were then treated with terminal alkynes to
perform Sonogashira cross-coupling reaction19c with palladium
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Table 1. Optimization of the Reaction Conditionsa
among different solvents screened, CH2Cl2 proved to be more
suitable for electrophilic cyclization (entries 7, 15, and 16). It is
noteworthy that when the reaction was continued for a longer time
(4 h), it resulted in an inseparable mixture of products (entry 17).
However, increasing the amount of base from 2.0 to 3.0 equiv had
nosignificant effect on the yield of the desired product 5(entry 18).
It is evident from the Table 1 that temperature and time play a
crucial role in the yield of the desired product 5. The combination
of I2 (2.0 equiv) and NaHCO3 (2.0 equiv) in CH2Cl2 (3.0 mL) at
0 °C was found to be the most appropriate for carrying out the
desired electrophilic iodocyclization.
Employing the optimized protocol, the scope of electrophilic
iodocyclization was then examined for alkynes bearing different
substituents for the synthesis of pyrrolo[1,2-a]quinolines. 1-
(2-(Substituted ethynyl)phenyl)-1H-pyrroles 3aÀt afforded
the desired pyrrolo[1,2-a]quinolines 5aÀt in 71À93% yields
(Table 2, entries 1À20).
T
t
yieldb
E+ (amt, equiv) base (amt, equiv) (°C) (h) (%)
entry
solvent
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
I2 (1.2)
I2 (2.0)
I2 (2.0)
ICl (2.0)
NBS (2.0)
I2 (2.0)
I2 (2.0)
ICl (2.0)
ICl (2.0)
ICl (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3(2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
25
25
25
25
25
0
1
1
2
1
1
1
2
1
2
2
2
2
2
2
2
2
4
2
26
48
c
c
It is evident from Table 2 that substituents attached to the
triple bond impart a major impact on the success of the regio-
selective cyclization as shown in compound A (Figure 1). The
presence of an electron-donating group para to the triple bond
increases the electron density on the distal end of the triple bond,
which thereby favors 6-endo-dig cyclization. This in turn in-
creased the efficiency of the reaction, and the cyclized products
5bÀh were obtained in good yields (Table 2, entries 2À8).
On the other hand, alkynes with substitution at the meta
position, 3i,j, afforded iodocyclized products 5i,j in compara-
tively lower yield (Table 2, entries 9 and 10). Alkyne 3k bearing
an electron-rich heterocycle, i.e., thiophene, proved to be favor-
able for the reaction and afforded the desired product 5k in 91%
yield (entry 11). An alkyne bearing a polyaromatic phenanthrene
group resulted in the corresponding iodocyclized product 5l in
87% yield (entry 12). Alkynes 3m,n having alkyl substituents, i.e.,
n-butyl and tert-butyl, gave the desired products 5m,n in 71% and
73% yields, respectively (entries 13 and 14). Alkynes with cyclic
alkyl substituents, 3oÀq, afforded the desired iodocyclized
products 5oÀq in 77À79% yield (entries 15À17). Alkynes 3r,
s having propargylhydroxyl and propargylphenoxy as substitu-
ents gave regioselective 6-endo-dig-cyclized products 5r,s in 74%
and 76% yields, respectively (entries 18 and 19). However, the
presence of an electron-withdrawing nitro group at the para
position to the triple bond of 3t provided an unidentified and
inseparable complex mixture (entry 20).
Further exploring the developed protocol for 3-methyl-
1-(2-(substituted phenylethynyl)phenyl)-1H-indoles 4aÀj af-
forded the desired indolo[1,2-a]quinolines 6aÀj in 79À92%
yields (Table 3, entries 1À10). However, 1-(2-(substituted
phenylethynyl)phenyl)-1H-indoles 4kÀn afforded the respec-
tive iodocyclized products 6kÀn in lower yield (entries 11À14).
The above observation could be explained as the effect of the
substituent at the 3 position of indole. The presence of a methyl
group at the 3 position of indole B (Figure 1) activates the indole
ring system, which facilitates the intramolecular cyclization via
formation of a tertiary carbocation, whereas in the case of un-
substituted indole C (Figure 1), decomposition occurred, which
might be due to the proton loss or polymerization.19a,d
35
43
82
0
0
35
c
0
10 CH2Cl2
11 CH2Cl2
12 CH2Cl2
13 CH2Cl2
14 CH2Cl2
15 CH3CN
16 1,4-dioxane
17 CH2Cl2
18 CH2Cl2
NaHCO3 (2.0) À78
KOtBu (2.0)
74
22
28
12
47
69
0
0
0
0
0
0
0
0
Cs2CO3 (2.0)
K3PO4 (2.0)
K2CO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (3.0)
trace
c
82
a All reactions were performed using 0.5 mmol of the alkyne 3a, base,
and 3.0 mL of solvent under inert conditions. b Isolated yields. c An
inseparable mixture of products was obtained.
3a (0.5 mmol) with 1.2 equiv of I2 and 2.0 equiv of NaHCO3 in
3.0 mL of CH2Cl2 at 25 °C for 1 h, and the iodocyclized product
5 was obtained in only 26% yield (Table 1, entry 1). However,
increasing the amount of I2 from 1.2 to 2.0 equiv afforded pro-
duct 5 in 48% yield (entry 2). When the reaction was allowed to
stir for 2 h, an inseparable mixture of products was obtained
(entry 3). When 2.0 equiv of ICl was taken instead of I2 and the
reaction was stirred for 1 h, an inseparable complex mixture of
products was obtained (entry 4). When 3a with 2.0 equiv of N-
bromosuccinimide (NBS) and 2.0 equiv of NaHCO3 in CH2Cl2
was stirred for 1 h, the desired cyclized product 5 was obtained in
35% yield (entry 5). When 3a reacted with 2.0 equiv of I2 and 2.0
equiv of NaHCO3 in CH2Cl2 for 1 h at 0 °C, the corresponding
iodocyclized product 5 was obtained in 43% yield, leaving behind
51% of the starting material (entry 6). Interestingly, when the
reaction was continued for 2 h, it afforded the iodocyclized
product 5 in 82% yield (entry 7). When 3a with 2.0 equiv of ICl
and 2.0 equiv of NaHCO3 in CH2Cl2 was stirred for 1 h at 0 °C,
the desired cyclized product 5 was obtained in 35% yield (entry 8).
When the reaction was allowed to stir for 2 h, an inseparable
mixture of products was obtained (entry 9). However, when the
reaction was stirred for 2 h at À78 °C, the corresponding
iodocyclized product 5 was obtained in 74% yield (entry 10).
Among different bases tested in this reaction system, NaHCO3
proved to be the most effective (entries 7 and 11À14). Also,
As discussed, the effect of an electron-donating group para
to the triple bond imparts the same effect on the indole moiety;
alkynes bearing an electron-donating group at the para position,
4bÀg and 4kÀn, afforded the corresponding iodocyclized
products 6bÀg and 6kÀn in good yields (Table 3, entries
2À7 and 11À14). Substitution at the meta and ortho positions
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Table 2. Synthesis of Pyrrolo[1,2-a]quinolines via I2-Mediated Electrophilic Ring Closurea
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Table 2. Continued
a All reactions were performed with 0.5 mmol of the alkynes 3aÀt, NaHCO3 (2.0 equiv), and I2 (2.0 equiv) in 3 mL of CH2Cl2 at 0 °C for 1.5À2.5 h
under inert conditions. b Isolated yields. c An inseparable mixture of products.
could be attributed to the anisotropic effect of the phenyl ring,
which is believed to be perpendicular to this methyl group. On the
basis of the above observation, the regioisomers indolo[1,2-a]-
quinoline 12 (obtained by the reduction of the iodo group of 6f)
and indolo[2,1-a]isoquinoline 13 (Figure 2) can be differen-
tiated. The presence of a methyl peak at 1.89 ppm in the 1H NMR
spectrum of 12 is due to the anisotropic effect as the phenyl ring
is perpendicular to the methyl group, whereas in indolo[2,1-a]
isoquinoline 13 the CH3 group attached to the indole ring
Figure 1. Effect of substituents on electrophilic cyclization.
appears at 2.88 ppm.
Furthermore, the disappearance of two characteristic peaks of
the alkynecarbon (around ∼80À99ppm) in13C NMR confirmed
the formation of cyclized product. Formation of the desired re-
gioselective 6-endo-dig-cyclized product was further confirmed
by crystallographic analysis20 of 5b and 6f.
On the basis of all the observations, an assumed pathway for
the formation of iodocyclized products 5 and 6 is illustrated in
Scheme 5. First, the Lewis acid (I2) coordinates to an acetylene
bond to form an iodonium complex, 14, which then undergoes
afforded iodocyclized products 6h,i in comparatively lower yields
(entries 8 and 9). Electron-rich thiophene alkyne 4j proved to be
favorable for the reaction and afforded desired product 6j in 92%
yield (entry 10). However, the presence of a methoxy group at
the 5 position of the indole ring provided an unidentified and
inseparable complex mixture (entry 15).
Further studies include analysis of 1H NMR, which on cycli-
zation of alkynes into products showed a significant shift of the
CH3 peak of the indole ring (from ∼2.3 to ∼1.6 ppm), which
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Table 3. Synthesis of Indolo[1,2-a]quinolines via I2-Mediated Electrophilic Ring Closurea
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Table 3. Continued
a All reactions were performed with 0.5 mmol of the alkynes 4aÀo, NaHCO3 (2.0 equiv), and I2 (2.0 equiv) in 3 mL of CH2Cl2 at 0 °C for 1.5À3.5 h
under inert conditions. b Isolated yields. c An inseparable mixture of products.
pyrrolo- and indolo[1,2-a]quinolines. Diversified quinoline nu-
clei with different substituents were generated in moderate to
excellent yields. In addition, the anisotropic observation of CH3
was aimed at uncovering the unique orientation of the phenyl
ring. The chemistry outlined here is extremely versatile and
accommodates various functional groups, which makes it ideal
for the generation of libraries. By further elaboration and diver-
sification of the various functionally substituted scaffolds, a wide
range of structurally and spatially diverse compounds can be pro-
Figure 2. Study of the anisotropic effect in 1H NMR.
duced. Also the iodine catalysis system will undoubtedly extend
applications of electrophilic reactions where replacement of
more expensive metal catalysts is desired.
intramolecular nucleophilic attack by the C2 of pyrrole and
indole on the activated triple bond to form intermediate 15.
π-Electrocyclization and successive aromatization of 15 led to
quinolines 5 and 6. The presence of NaHCO3 was crucial for a
clean, high-yielding reaction. NaHCO3 is presumed to neutralize
’ EXPERIMENTAL SECTION
the byproduct HI of the electrophilic cyclization.
General Method. 1H and 13C NMR spectra were recorded at 300
and 75 MHz or 400 and 100 MHz, respectively. Thin-layer chromatog-
raphy was performed using commercially prepared 60 F254 silica gel
plates, and visualization was effected with short-wavelength UV light
(254 nm). All melting points are uncorrected. High-resolution mass
spectra were recorded on a double-focusing magnetic sector mass spec-
trometer using EI at 70 eV. Anhydrous forms of all reagents such as ethyl
ether, hexanes, ethyl acetate, molecular iodine, CH2Cl2, 3-methyl-1H-
indole, 1H-indole, 1H-pyrrole, 5-methoxy-1H-indole, terminal alkynes,
An interesting feature of the electrophilic cyclization is the
retention of the electrophile (I) on the polycyclic aromatic
products, which could be further elaborated. Various palladium-
and copper-catalyzed reactions can be performed for diversifica-
tion of the quinoline moiety, and thereby, biological diversity can
be introduced (Scheme 6).
In summary, the results of the above studies have demon-
strated the feasible and efficient approach for the synthesis of
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Scheme 5. Probable Mechanism
1-(2-((4-Methoxyphenyl)ethynyl)phenyl)-1H-pyrrole (3e). The pro-
duct was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.60
(d, J = 7.4 Hz, 1H), 7.37À7.32 (m, 4H), 7.27À7.24 (m, 1H), 7.16 (t, J =
2.2 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 6.34 (t, J = 2.2 Hz, 2H), 3.79 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 159.7, 141.8, 133.3, 132.9, 128.8,
126.2, 124.8, 121.7, 118.4, 115.0, 114.0, 109.0, 93.9, 85.2, 55.3; HRMS
m/z calcd for C19H15NO 273.1154, found 273.1147.
4-((2-(1H-Pyrrol-1-yl)phenyl)ethynyl)-N,N-dimethylaniline (3f). The
product was obtained as a white solid: mp 64À66 °C; 1H NMR
(400 MHz, CDCl3) δ 7.63 (d, J = 7.4 Hz, 1H); 7.36À7.33 (m, 4H),
7.31À7.26 (m, 1H), 7.23 (t, J = 2.2 Hz, 2H), 6.66 (d, J = 9.5Hz, 2H), 6.39
(t, J = 2.2 Hz, 2H), 3.01 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 150.1,
141.5, 133.0 132.6, 128.2, 126.1, 124.7, 121.7, 118.9, 11.7, 109.7, 108.9,
95.3, 84.6, 40.1; HRMS m/z calcd for C20H18N2 286.1470, found
286.1474.
1-(2-(Biphenyl-4-ylethynyl)phenyl)-1H-pyrrole (3g). The product
1
was obtained as a colorless oil: H NMR (400 MHz, CDCl3) δ 7.65
(dd, J = 1.5, 7.4 Hz, 1H), 7.60À7.54 (m, 4H), 7.50À7.47 (m, 2H),
7.46À7.33 (m, 5H), 7.31À7.27 (m, 1H), 7.19 (t, J = 2.2 Hz, 2H), 6.37 (t,
J = 2.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 142.0, 141.1, 140.3,
133.5, 131.8, 129.2, 128.8, 127.6, 126.9, 126.2, 124.9, 121.83, 121.76,
118.1, 109.2, 93.7, 87.2; HRMS m/z calcd for C24H17N 319.1361, found
319.1355.
Et3N, and the palladium salts were used directly as obtained commer-
cially unless otherwise noted.
General Procedure for the Formation of the 1-(2-(Aryl-
ethynyl)phenyl)-1H-pyrroles 3aÀt and 1-(2-(Arylethynyl)-
phenyl)-1H-indoles 4aÀo. To a solution of 1.0 mmol of 1-(2-
iodophenyl)-1H-indole/1-(2-iodophenyl)-1H-pyrrole and PdCl2(PPh3)2
(5.0 mol %) in CH3CN (5.0 mL) was added CuI (1.0 mol %). The
reaction was flushed with N2. To the reaction mixture were added Et3N
(2.0 equiv) and 1.2 equiv of the terminal alkyne. The reaction mixture was
allowed to stir at 60 °C for 1À2 h. The disappearance of the starting
material was determined by TLC. The resulting solution was filtered
and washed with saturated aq NaCl solution and extracted with ethyl
acetate (2 Â 15 mL). The combined organic fractions were dried over
anhydrous Na2SO4 and concentrated under vacuum to yield the crude
product. The crude product was purified by column chromatography on
silica gel using ethyl acetate/hexane as the eluent.
1-(2-(Phenylethynyl)phenyl)-1H-pyrrole (3a). The product was ob-
tained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.64À7.62 (m,
1H), 7.43À7.40 (m, 2H), 7.38À7.36 (m, 1H), 7.34À7.26 (m, 5H), 7.17
(t, J = 2.2 Hz, 2H), 6.35 (t, J = 2.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 142.0, 1335, 131.4, 129.2, 128.4, 128.3, 126.2, 124.9, 122.9,
121.7, 118.0, 109.2, 93.7, 86.5; HRMS m/z calcd for C18H13N 243.1048,
found 243.1044.
1-(2-(p-Tolylethynyl)phenyl)-1H-pyrrole (3b). The product was ob-
tained as a brown oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 9.1 Hz,
1H), 7.32À7.28 (m, 2H), 7.25À7.23 (m, 1H), 7.21À7.17 (m, 2H),
7.10À7.09 (m, 2H), 7.05À7.03 (m, 2H), 6.28À6.27 (m, 2H), 2.27 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 142.0, 138.7, 133.5, 131.4, 129.1,
126.3, 124.9, 121.8, 120.0, 118.4, 109.1, 93.8, 85.9, 21.7; HRMS m/z
calcd for C19H15N 257.1204, found 257.1217.
1-(2-((4-Ethylphenyl)ethynyl)phenyl)-1H-pyrrole (3c). The product
was obtained as a brown oil: 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J =
8.2 Hz, 1H), 7.33À7.28 (m, 3H), 7.27À7.26 (m, 1H), 7.20À7.18
(m, 1H), 7.10À7.07 (m, 4H), 6.28À6.27 (m, 2H), 2.57 (q, J = 7.3 Hz,
2H), 1.15 (t, J= 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ145.1, 142.0,
133.6, 131.5, 129.1, 128.0, 126.3, 124.9, 121,8, 120.2, 118.4, 109.3, 94.2,
85.9, 28.9, 15.4; HRMS m/z calcd for C20H17N 271.1361, found 271.1356.
1-(2-((4-Butylphenyl)ethynyl)phenyl)-1H-pyrrole (3d). The product
was obtained as a white oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J =
8.9 Hz, 1H), 7.32À7.24 (m, 4H), 7.21À7.17 (m, 1H), 7.10À7.09 (m,
2H), 7.05 (d, J = 8.2 Hz, 2H), 6.27 (t, J = 2.3 Hz, 2H), 2.52 (t, J = 7.8 Hz,
2H), 1.50 (p, J = 7.7 Hz, 2H), 1.26 (st, J = 7.8 Hz, 2H), 0.84 (t, J = 7.3 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 143.7, 142.0, 133.6, 131.4, 129.0,
128.5, 126.3, 124.9, 121.8, 120.1, 118.4, 109.2, 94.1, 85.9, 35.7, 33.4, 22.3,
14.01; HRMS m/z calcd for C22H21N 299.1674, found 299.1681.
1-(2-((6-Methoxynaphthalen-2-yl)ethynyl)phenyl)-1H-pyrrole (3h).
1
The product was obtained as a colorless oil: H NMR (400 MHz,
CDCl3) δ 7.79 (s, 1H), 7.62À7.57 (m, 4H), 7.37À7.21 (m, 3H), 7.14 (t,
J = 2.2 Hz, 2H), 7.09À7.06 (m, 1H), 7.02 (d, J = 2.2 Hz, 1H), 6.31 (t, J =
2.6 Hz, 2H), 3,84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.4, 141.9,
134.2, 133.5, 131.2, 129.4, 129.0, 128.7, 126.8, 126.2, 124.9, 121.8, 119.4,
118.3, 117.8, 109.2, 105.8, 94.4, 86.2, 55.3; HRMS m/z calcd for
C23H17NO 323.1310, found 323.1319.
1-(2-(m-Tolylethynyl)phenyl)-1H-pyrrole (3i). The product was ob-
tained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.63À7.60 (m,
1H), 7.39À7.31 (m, 3H), 7.28À7.19 (m, 4H), 7.17 (t, J = 2.2 Hz, 2H),
6.35 (t, J = 2.2 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
141.9, 137.9, 133.6, 131.9, 129.4, 129.1, 128.5, 128.2, 126.2, 124.8, 122.7,
121.7, 118.1, 109.2, 93.9, 86.1, 21.2; HRMS m/z calcd for C19H15N
257.1204, found 257.1211.
1-(2-((3-Methoxyphenyl)ethynyl)phenyl)-1H-pyrrole (3j). The pro-
duct was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.63
(dd, J = 1.5, 8.1 Hz, 1H), 7.41À7.34 (m, 2H), 7.30À7.19 (m, 2H), 7.17
(t, J = 2.2 Hz, 2H), 7.02 (d, J = 7.3 Hz, 1H), 6.95À6.94 (m, 1H), 6.87
(dd, J = 2.2, 7.32 Hz, 1H), 6.35 (t, J = 1.8 Hz, 2H), 3.79 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ 159.2, 142.1, 133.5, 129.3, 129.2, 124.9,
123.9, 121.8, 118.0, 117.0, 116.1, 115.1, 109.2, 93.7, 86.3, 55.2; HRMS
m/z calcd for C19H15NO 273.1154, found 273.1164.
1-(2-(Thiophene-3-ylethynyl)phenyl)-1H-pyrrole (3k). The product
was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.60 (dd,
J = 1.5, 8.0 Hz, 1H), 7.43 (d, J = 2.9 Hz, 1H), 7.40À7.32 (m, 3H),
7.27À7.24 (m, 1H), 7.15 (t, J = 2.2 Hz, 2H), 7.12À7.09 (m, 1H), 6.34 (t,
J = 2.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 141.9, 133.4, 129.6,
129.1, 128.9, 126.2, 125.3, 124.9, 122.0, 121.7, 118.0, 109.2, 89.1, 86.0;
HRMS m/z calcd for C16H11NS 249.0612, found 249.0608.
1-(2-(Phenanthren-9-ylethynyl)phenyl)-1H-pyrrole (3l). The pro-
1
duct was obtained as a white solid: mp 80 °C; H NMR (400 MHz,
CDCl3) δ 8.56 (t, J = 8.8 Hz, 2H), 8.08 (dd, J = 1.5, 8.1 Hz, 1H), 7.91
(s, 1H), 7.76 (dd, J = 1.5, 8.1 Hz, 1H), 7.71 (dd, J = 1.4, 7.3 Hz, 1H),
7.61À7.48 (m, 4H), 7.35À7.25 (m, 3H), 7.16À7.14 (m, 2H), 6.36 (t, J =
2.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 142.1, 133.8, 132.0, 131.1,
130.9, 130.3, 129.9, 128.6, 127.5, 127.26, 127.00, 126.90, 126.6, 125.4,
122.6, 121.9, 119.4, 118.8, 109.5, 92.2, 90.7; HRMS m/z calcd for
C26H17N 343.1361, found 343.1366.
1-(2-(Hex-1-ynyl)phenyl)-1H-pyrrole (3m). The product was ob-
tained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.49
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ARTICLE
Scheme 6. Diversification of the Quinoline Nucleusa
a Key: (A) Suzuki reaction,21 (B) Heck reaction,22 (C) alkyne annulation,23 (D) Ullmann-type coupling,24,19e,19f (E) reduction of iodine.25
(d, J = 8.0 Hz, 1H), 7.33À7.19 (m, 3H), 7.09 (t, J = 2.2 Hz, 2H), 6.29 (t, J
= 2.2 Hz, 2H), 2.34 (t, J = 6.6 Hz, 2H), 1.55À1.48 (m, 2H), 1.43À1.34
(m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 141.9,
133.9, 128.4, 126.1, 124.8, 121.5, 118.8, 108.9, 95.3, 30.4, 21.9, 19.2,
13.6; HRMS m/z calcd for C16H17N 223.1361, found 223.1359.
1-(2-(3,3-Dimethylbut-1-ynyl)phenyl)-1H-pyrrole (3n). The product
was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.40 (dd,
J = 1.4, 7.8 Hz, 1H), 7.23À7.20 (m, 2H), 7.14À7.12 (m, 1H), 7.02 (t, J =
2.2 Hz, 2H), 6.21 (t, J = 2.2 Hz, 2H), 1.15 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ141.9, 133.6, 128.4, 126.0, 124.7, 121.6, 118.7, 108.7, 103.0, 76.0,
30.5, 29.7; HRMS m/z calcd for C16H17N 223.1361, found 223.1369.
1-(2-(Cyclohexylethynyl)phenyl)-1H-pyrrole (3o). The product was
obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.42 (dd, J =
1.4, 7.8 Hz, 1H), 7.25À7.718 (m, 2H), 7.15À7.711 (m, 1H), 7.02 (t, J =
2.3 Hz, 2H), 6.22 (t, J = 1.8 Hz, 2H), 2.48À2.43 (m, 1H), 1.73À1.69 (m,
2H), 1.63À1.58 (m, 2H), 1.46À1.35 (m, 4H), 1.26À1.83 (m, 2H).);
13C NMR (100 MHz, CDCl3) δ 141.3, 133.8, 128.3, 126.0, 124.7, 121.6,
118.8, 108.8, 99.2, 32.2, 29.7, 25.8, 24.7; HRMS m/z calcd for C18H19N
249.1517, found 249.1522.
1-(2-(Cyclopentylethynyl)phenyl)-1H-pyrrole (3p). The product was
obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.41 (dd, J =
1.5, 7.3 Hz, 1H), 7.25À7.17 (m, 2H), 7.15À7.10 (m, 1H), 7.02 (t, J = 2.2
Hz, 2H), 6.22 (t, J = 2.2 Hz, 2H), 2.73À2.66 (m, 1H), 1.84À1.79 (m,
2H), 1.65À1.54 (m, 4H), 1.53À1.45 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 141.9, 133.7, 128.3, 126.0, 124.7, 121.5, 118.8, 108.8, 99.4,
33.4, 30.8, 24.9; HRMS m/z calcd for C17H17N 235.1361, found
235.1359.
1-(2-(Cyclopropylethynyl)phenyl)-1H-pyrrole (3q). The product was
obtained as a colorless liquid: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd,
J = 1.44, 7.3 Hz, 1H), 7.32À7.17 (m, 3H), 7.06 (t, J = 2.6 Hz, 2H), 6.29
(t, J = 2.6 Hz, 2H), 1.39À1.33 (m, 1H), 0,83À0.70 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 141.6, 133.3, 127.9, 125.7, 124.4, 121.2, 118.4,
108.5, 97.9, 72.1, 8.1, 0.0; HRMS m/z calcd for C15H13N 207.2700,
found 207.2698.
3-(2-(1H-Pyrrol-1-yl)phenyl)prop-2-yn-1-ol (3r). The product was
obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J =
1.5, 7.3 Hz, 1H), 7.40À7.36 (m, 1H), 7.31À7.23 (m, 2H), 7.07 (t, J =
2.2 Hz, 2H), 6.31 (t, J = 2.2 Hz, 2H), 4.39 (s, 2H), 1.77 (s, 1H); 13C
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ARTICLE
NMR (100 MHz, CDCl3) δ 142.1, 133.8, 129.4, 126.3, 125.0, 121.7,
117.5, 109.2, 91.8, 82.6, 51.6; HRMS calcd for C13H11NO 197.0841,
found 197.0844.
1-(2-(3-Phenoxyprop-1-ynyl)phenyl)-1H-pyrrole (3s). The product
was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.55 (dd,
J = 1.5, 8.1 Hz, 1H), 7.40À7.36 (m, 1H), 7.32À7.21 (m, 4H), 7.04 (t, J =
2.2 Hz, 2H), 7.01À6.95 (m, 3H), 6.30 (t, J = 2.2 Hz, 2H), 4.85 (s, 2H);
13C NMR (100 MHz, CDCl3) δ 157.6, 142.3, 134.3, 129.7, 129.4, 126.2,
124.9, 121.4, 116.9, 114.9, 109.4, 88.5, 84.0, 56.4; HRMS m/z calcd for
C19H15NO 273.1154, found 273.1147.
84.9, 40.3, 9.9; HRMS m/z calcd for C25H22N2 350.1783, found
350.1790.
3-Methyl-1-(2-(m-tolylethynyl)phenyl)-1H-indole (4h). The product
was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.69À7.64
(m, 1H), 7.47À7.41 (m, 2H), 7.37À7.32 (m, 2H), 7.28 (s, 1H), 7.24À
7.20(m, 3H), 7.18À7.06 (m, 2H), 6.96À6.90 (m, 1H), 6.85 (s, 1H), 2.42
(s, 3H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 140.9, 137.8, 136.6,
133.2, 132.1, 130.0, 129.3, 128.9, 128.2, 128.0, 127.2, 126.6, 122.6, 121.9,
120.5, 119.5, 118.8, 115.9, 111.8, 111.6, 94.7, 86.2, 21.3, 9.6; HRMS m/z
calcd for C24H19N 321.1517, found 321.1526.
3-Methyl-1-(2-(phenylethynyl)phenyl)-1H-indole (4a). The product
was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.71 (dd,
J = 7.6, 1.6 Hz, 1H), 7.68À7.66 (m, 1H), 7.52À7.45 (m, 2H), 7.40À7.36
(m, 2H), 7.30 (d, J = 1.6 Hz, 1H), 7.25À7.19 (m, 5H), 7.12À7.09 (m,
2H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 141.1, 136.8, 133.6,
131.5, 129.5, 129.3, 128.5, 128.3, 126.96, 126.87, 126.81, 123.0, 122.2,
120.6, 119.7, 119.1, 112.1, 111.2, 94.7, 86.8, 9.9; HRMS m/z calcd for
C23H17N 307.1361, found 307.1356.
3-Methyl-1-(2-(o-tolylethynyl)phenyl)-1H-indole (4i). The product
was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.70À7.55
(m, 2H), 7.40À7.34 (m, 2H), 7.31À7.28 (m, 2H), 7.23 (s, 1H), 7.20À
7.06 (m, 2H), 6.95À6.86 (m, 4H), 2.38 (s, 3H), 2.21 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 140.8, 137.9, 136.6, 133.2, 132.2, 130.0, 129.6,
128.9, 128.2, 128.0, 127.2, 126.6, 122.2, 121.9, 120.5, 119.5, 118.2, 115.7,
111.8, 111.6, 94.7, 86.2, 21.4, 9.6; HRMS m/z calcd for C24H19N
321.1517, found 321.1509.
3-Methyl-1-(2-(p-tolylethynyl)phenyl)-1H-indole (4b). The product
was obtained as a colorless liquid: H NMR (300 MHz, CDCl3) δ
3-Methyl-1-(2-(thiophene-3-ylethynyl)phenyl)-1H-indole (4j). The
product was obtained as a colorless oil: 1H NMR (400 MHz, CDCl3) δ
7.70À7.66 (m, 2H), 7.49À7.44 (m, 2H), 7.39À7.35 (m, 2H), 7.27 (d,
J = 5.0 Hz, 1H), 7.23À7.21 (m, 2H), 7.19 (dd, J = 2.0, 3.2 Hz, 1H), 7.11
(d, J = 3.2 Hz, 1H), 6.79 (d, J = 5.2 Hz, 1H), 2.44 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 141.1, 136.8, 133.3, 129.7, 129.5, 129.2, 129.0, 126.9,
126.8, 126.7, 125.3, 122.1, 120.6, 119.7, 119.1, 111.3, 111.1, 90.0, 86.3,
9.9; HRMS m/z calcd for C21H15NS 313.0925, found 313.0919.
1-(2-(p-Tolylethynyl)phenyl)-1H-indole (4k). The product was ob-
tained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.72À7.68 (m,
2H), 7.52À7.46 (m, 3H), 7.43À7.36 (m, 2H), 7.22À7.16 (m, 2H),
7.12À7.03 (m, 2H), 6.91À6.89 (m, 1H), 6.82 (s, 1H), 6.70 (d, J =
3.3 Hz, 1H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 140.7, 137.8,
136.4, 133.3, 132.0, 129.3, 129.1, 129.0, 128.3, 128.0, 127.1, 126.9, 122.4,
122.0, 120.8, 120.1, 111.1, 102.8, 94.7, 85.8, 21.1; HRMS m/z calcd for
C23H17N 307.1361, found 307.1369.
1-(2-((4-Ethylphenyl)ethynyl)phenyl)-1H-indole (4l). The product
was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.71À7.66
(m, 2H), 7.50À7.34 (m, 5H), 7.21À7.13 (m, 2H), 7.04À6.97 (m, 4H),
6.69 (d, J = 3.0, 1H), 2.56 (q, J = 7.8, 2H), 1.16 (t, J = 7.5, 3H); 13C NMR
(75 MHz, CDCl3) δ 144.9, 140.6, 136.5, 133.3, 131.4, 129.1, 128.9,
127.8, 127.1, 127.0, 122.0, 121.1, 120.8, 120.1, 119.9, 114.7, 111.1, 102.8,
94.8, 85.6, 28.8, 15.5; HRMS m/z calcd for C24H19N 321.1517, found
321.1525.
1
7.60À7.55 (m, 2H), 7.40À7.32 (m, 2H), 7.28À7.20 (m, 3H), 7.15À
7.07 (m, 2H), 6.96À6.88 (m, 4H), 2.33 (s, 3H), 2.21 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 140.8, 138.5, 136.6, 133.2, 131.2, 128.9, 126.6,
121.9, 120.6, 119.7, 119.5, 118.8, 111.8, 110.9, 94.7, 85.9, 21.5, 9.7;
HRMS m/z calcd for C24H19N 321.1517, found 321.1525.
1-(2-((4-Ethylphenyl)ethynyl)phenyl)-3-methyl-1H-indole (4c). The
product was obtained as a colorless liquid: 1H NMR (300 MHz, CDCl3)
δ 7.62À7.56 (m, 2H), 7.42À7.36 (m, 2H), 7.30À7.27 (m, 2H), 7.21À
7.07 (m, 3H), 6.99À6.92 (m, 4H), 2.51 (q, J = 7.5 Hz, 2H), 2.34 (s, 3H),
1.11 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 144.8, 140.8,
136.6, 133.3, 131.4, 129.4, 128.9, 127.8, 126.7, 121.9, 120.7, 120.0, 119.5,
118.5, 111.8, 111.0, 94.8, 85.9, 28.8, 15.3, 9.7; HRMS m/z calcd for
C25H21N 335.1674, found 335.1666.
1-(2-((4-Butylphenyl)ethynyl)phenyl)-3-methyl-1H-indole (4d). The
product was obtained as a colorless oil: 1H NMR (300 MHz, CDCl3) δ
7.68À7.64 (m, 2H), 7.48À7.42 (m, 2H), 7.36À7.27 (m, 3H), 7.23À7.17
(m, 2H), 7.10À6.83 (m, 4H), 2.54 (t, J = 7.2 Hz, 2H), 2.41 (s, 3H), 1.53
(p, J = 6.9 Hz, 2H), 1.30 (st, J = 7.2 Hz, 2H), 0.89 (t, J = 7.2 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) δ 143.5, 140.8, 136.6, 133.3, 131.3, 129.3, 128.8,
128.3, 126.77, 126.69, 121.9, 120.7, 120.0, 119.5, 118.9, 111.8, 111.0,
94.8, 85.9, 35.6, 33.3, 22.3, 13.9, 9.7; HRMS m/z calcd for C27H25N
363.1987, found 363.1981.
1-(2-((4-tert-Butylphenyl)ethynyl)phenyl)-3-methyl-1H-indole (4e).
The product was obtained as a white oil: 1H NMR (300 MHz, CDCl3) δ
7.66À7.63 (m, 2H), 7.46À7.33 (m, 5H), 7.25À7.17 (m, 4H), 7.03 (d, J
= 8.4 Hz, 2H), 2.42(s, 3H), 1.26 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
151.6, 140.8, 136.6, 133.3, 131.1, 129.0, 128.8, 126.74, 126.64, 125.1,
121.9, 120.7, 119.8, 119.5, 118.8, 111.8, 111.0, 94.6, 85.9, 34.7, 31.3, 9.7;
HRMS m/z calcd for C27H25N 363.1987, found 363.1988.
1-(2-((4-Methoxyphenyl)ethynyl)phenyl)-3-methyl-1H-indole (4f).
The product was obtained as a viscous yellow oil: 1H NMR (400 MHz,
CDCl3) δ 7.69À7.65 (m, 2H), 7.50À7.42 (m, 2H), 7.38À7.36 (m, 2H),
7.30 (s, 1H), 7.22À7.19 (m, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.75 (d, J =
8.4 Hz, 2H), 3.79 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.8, 140.8, 136.8, 133.2, 133.0, 129.5, 128.8, 126.92, 126.86, 126.83,
122.1, 121.0, 119.7, 119.0, 115.1, 114.0, 111.9, 111.3, 94.8, 85.6, 55.5,
9.9; HRMS m/z calcd for C24H19NO 337.1467, found 337.1471.
N,N-Dimethyl-4-((2-(3-methyl-1H-indol-1-yl)phenyl)ethynyl)ani-
line (4g). The product was obtained as a white solid: mp 57À58 °C; 1H
NMR (400 MHz, CDCl3) δ 7.71À7.68 (m, 2H), 7.50 (d, J = 7.6 Hz,
1H), 7.42À7.40 (m, 2H), 7.38À7.34 (m, 2H), 7.27À7.21 (m, 2H), 7.03
(d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 2.96 (s, 6H), 2.48 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 150.3, 140.5, 136.8, 133.0, 132.6, 129.5,
128.2, 126.9, 126.8, 122.0, 121.5, 119.5, 118.9, 111.8, 111.3, 109.7, 96.2,
1-(2-((4-Methoxyphenyl)ethynyl)phenyl)-1H-indole (4m). The pro-
duct was obtained as a colorless oil: H NMR (400 MHz, CDCl3) δ
1
7.75À7.70 (m, 2H), 7.53À7.51 (m, 2H), 7.46 (dd, J = 2.0, 7.2 Hz, 1H),
7.42À7.38 (m, 2H), 7.21À7.18 (m, 2H), 7.02 (dd, J = 2.0, 4.8 Hz, 2H),
6.77À6.73 (m, 3H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.9, 140.6, 136.6, 133.2, 133.1, 129.3, 128.9, 128.8, 127.3, 127.1, 122.1,
121.4, 120.9, 120.3, 114.9, 114.0, 111.3, 102.9, 94.9, 85.2, 55.4; HRMS
m/z calcd for C23H17NO 323.1310, found 323.1305.
4-((2-(1H-Indol-1-yl)phenyl)ethynyl)-N,N-dimethylaniline (4n). The
product was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ
7.68À7.64 (m, 2H), 7.51À7.46 (m, 2H), 7.42À7.35 (m, 3H), 7.21À7.15
(m, 3H), 6.95 (d, J = 9.0 Hz, 2H), 6.51 (d, J = 9.0 Hz, 2H), 2.92 (s, 6H);
13C NMR (75 MHz, CDCl3) δ 150.2, 140.1, 136.5, 132.8, 132.6, 129.3,
128.8, 128.1, 127.0, 126.9, 121.9, 121.8, 120.7, 120.0, 111.6, 111.2, 109.5,
102.5, 96.1, 84.4, 40.1; HRMS m/z calcd for C24H20N2 336.1626, found
336.1620.
5-Methoxy-1-(2-(p-tolylethynyl)phenyl)-1H-indole (4o). The pro-
1
duct was obtained as a brown liquid: H NMR (400 MHz, CDCl3) δ
7.59 (d, J = 7.8 Hz, 1H), 7.49À7.42 (m, 1H), 7.40À7.31 (m, 3H), 7.28À
7.25 (m, 1H), 7.19À7.12 (m, 2H), 7.08 (d, J = 2.3 Hz, 1H), 7.01À6.99
(m, 1H), 6.81À6.75 (m, 2H), 6.53 (d, J = 3.2 Hz, 1H), 3.79 (s, 3H), 2.21
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.4, 140.6, 138.5, 133.3,
5679
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131.2, 129.6, 128.9, 127.1, 126.7, 120.7, 119.6, 114.1, 112.0, 111.8, 108.6,
102.6, 102.4, 101.8, 94.6, 85.6, 55.9, 21.4; HRMS m/z calcd for
C24H19NO 337.1467, found 337.1460.
104.7, 93.1, 34.6, 33.0, 21.7, 13.7; HRMS m/z calcd for C22H20IN 425.0640,
found 425.0635.
5-Iodo-4-(4-methoxyphenyl)pyrrolo[1,2-a]quinoline (5e). The pro-
duct was obtained as a brown solid: mp 127À130 °C; 1H NMR {400
MHz, (CD3)2SO} δ 8.34À8.33 (m, 1H), 8.23 (d, J = 8.0 Hz, 1H), 8.04
(d, J = 8.1 Hz, 1H), 7.63 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.26
(d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 6.68 (t, J = 3.6 Hz, 1H), 5.91
(dd, J = 1.5, 3.7 Hz, 1H), 3.83 (s, 3H); 13C NMR {100 MHz,
(CD3)2SO} δ 159.0, 138.3, 134.1, 133.7, 131.9, 131.4, 130.4, 129.1,
124.9, 124.0, 115.0, 114.3, 113.8, 113.1, 104.8, 93.6, 55.1; HRMS m/z
calcd for C19H14INO 399.0120, found 399.0131.
General Procedure for the Synthesis of 5-Iodopyrrplo[1,2-
a]quinolines 5aÀt and 5-Iodoindolo[1,2-a]quinolines 6aÀo.
To a solution of 0.5 mmol of 1-(2-(arylethynyl)phenyl)-1H-pyrroles/
1-(2-(arylethynyl)phenyl)-1H-indoles in a 5.0 mL round-bottom flask
in 2.0 mL of CH2Cl2 was added 2 equiv of NaHCO3. This was followed
by dropwise addition of I2 solution (2 equiv of I2 in 1 mL of CH2Cl2).
The reaction mixture was allowed to stir at 0 °C for 1.5À3.5 h under
inert conditions. The disappearance of the starting material was deter-
mined by TLC. The reaction mixture was then quenched with saturated
aq sodium thiosulfate solution. The resulting solution was extracted with
ethyl acetate (2 Â 10 mL). The combined organic fractions were dried
over anhydrous Na2SO4 and concentrated under vacuum to yield the
crude product. The crude product was purified by column chromatog-
raphy on silica gel (100À200 mesh) using hexane as the eluent.
5-Iodo-4-phenylpyrrolo[1,2-a]quinoline (5a). The product was ob-
tained as a brown viscous oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.35À
8.34 (m, 1H), 8.24 (d, J = 8.1 Hz, 1H), 8.06À8.03 (m, 1H), 7.65À7.61
(m, 1H), 7.54À7.44 (m, 4H), 7.33À7.31 (m, 2H), 6.68 (t, J = 3.3 Hz,
1H), 5.85 (dd, J = 1.4, 3.7 Hz, 1H); 13C NMR {100 MHz, (CD3)2SO} δ
141.7, 138.5, 133.6, 132.0, 131.2, 129.2, 129.0, 128.5, 128.2, 124.9, 123.9,
115.0, 114.3, 113.1, 104.7, 93.0; HRMS m/z calcd for C18H12IN
369.0014, found 369.0009.
4-(5-Iodopyrrolo[1,2-a]quinolin-4-yl)-N,N-dimethylaniline (5f). The
1
product was obtained as a brown solid: mp 142À145 °C; H NMR
(400 MHz, CDCl3) δ 8.16 (dd, J = 1.4, 8.0 Hz, 1H), 7.88À7.87 (m, 1H),
7.83 (d, J = 8.0 Hz, 1H), 7.55À7.51 (m, 1H), 7.40À7.36 (m, 1H),
7.28À7.25 (m, 2H), 6.84À6.81 (m, 2H), 6.69 (t, J = 3.3 Hz, 1H), 6.15
(dd, J = 1.5, 3.7 Hz, 1H), 3.05 (s, 6H); 13C NMR {100 MHz, (CD3)2SO}
δ 149.9, 133.6, 131.7, 129.9, 128.9, 128.6, 127.9, 124.8, 124.2, 123.1,
114.9, 114.1, 113.0, 111.6, 104.9, 93.6, 39.9; HRMS m/z calcd for
C20H17IN2 412.0436, found 412.0429.
4-(Biphenyl-4-yl)-5-iodopyrrolo[1,2-a]quinoline (5g). The product
was obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.37 (d,
1H, J = 2.2 Hz), 8.26 (d, 1H, J = 8.0 Hz), 8.07 (dd, 1H, J = 1.5, 8.1 Hz),
7.83 (d, 2H, J = 8.0 Hz), 7.79 (d, 2H, J = 6.6 Hz), 7.66 (t, 1H, J = 7.3 Hz),
7.51À7.48 (m, 4H), 7.44À7.39 (m, 2H), 6.71 (t, 1H, J = 3.3 Hz), 5.95
(dd, 1H, J = 1.5, 4.9 Hz); 13C NMR {100 MHz, (CD3)2SO} δ 140.9,
139.6. 139.6, 138.2, 133.7, 132.0, 131.1, 129.8, 129.3, 129.0, 127.7, 126.7,
124.9, 123.9, 115.0, 114.4, 113.2, 104.8, 93.1; HRMS m/z calcd for
C24H16IN 445.0327, found 445.0342.
5-Iodo-4-(6-methoxynaphthalen-2-yl)pyrrolo[1,2-a]quinoline (5h).
The product was obtained as a brown solid: mp 152À155 °C; 1H NMR
{400 MHz, (CD3)2SO} δ 8.34À8.33 (m, 1H), 8.23 (d, J = 8.1 Hz, 1H),
8.05 (dd, J = 1.5, 8.0 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.8 Hz,
1H), 7.80 (m, 1H), 7.65À7.60 (m, 1H), 7.45 (t, J = 7.9 Hz, 1H),
7.39À7.36 (m, 2H), 7.18 (dd, J = 2.9, 8.8 Hz, 1H), 6.66 (t, J = 3.8 Hz1H),
5.88 (dd, J = 1,5, 3.8 Hz, 1H), 3.88 (s, 3H); 13C NMR {100 MHz,
(CD3)2SO} δ 157.8, 138.6, 136.9, 134.0, 133.6, 132.0, 131.4, 129.6,
129.3, 128.2, 127.9, 127.6, 126.9, 124.9, 124.0, 118.9, 115.0, 114.3, 113.2,
106.0, 104.9, 93.5, 55.3; HRMS m/z calcd for C23H16INO 449.0277,
found 449.0259.
5-Iodo-4-m-tolylpyrrolo[1,2-a]quinoline (5i). The product was ob-
tained as a brown solid: mp 89À91 °C; 1H NMR {400 MHz,
(CD3)2SO} δ 8.35À8.33 (m, 1H), 8.24 (d, J = 7.4 Hz, 1H), 8.05 (dd,
J = 1.4, 8.0 Hz, 1H), 7.64 (dt, J = 1.5, 7.4 Hz, 1H), 7.49À7.39 (m, 2H),
7.28 (d, J = 7.3 Hz, 1H), 7.14À7.10 (m, 2H), 6.68 (t, J = 2.9 Hz, 1H),
5.88 (dd, J = 1.5, 3.7 Hz, 1H), 2.37 (s, 3H); 13C NMR {100 MHz,
(CD3)2SO} δ 141.7, 138.6, 137.6, 133.6, 132.0, 131.2, 129.5, 129.2,
128.9,128.2, 126.2, 124.9, 123.9, 115.0, 114.3, 113.1, 104.8, 92.9, 21.1;
HRMS m/z calcd for C19H14IN 383.0171, found 383.0164.
5-Iodo-4-(3-methoxyphenyl)pyrrolo[1,2-a]quinoline (5j). The pro-
duct was obtained as a brown solid: mp 109À112 °C; 1H NMR
{400 MHz, (CD3)2SO} δ 8.35À8.34 (m, 1H), 8.24 (d, J = 3.2 Hz,
1H), 8.06 (dd, J = 1.5, 8.8 Hz, 1H), 7.66À7.62 (m, 1H), 7.49À7.42 (m,
2H), 7.06À7.03 (m, 1H), 6.90À6.88 (m, 2H), 6.69 (t, J = 2.9 Hz, 1H),
5.93À5.92 (m, 1H), 3.78 (s, 3H); 13C NMR {100 MHz, (CD3)2SO} δ
159.1, 143.0, 138.4, 133.6, 132.0, 131.0, 129.7, 129.3, 124.9, 123.9, 121.3,
115.0, 114.8, 114.3, 113.6, 113.1, 104.7, 92.9, 55.1; HRMS m/z calcd for
C19H14INO 399.0120, found 399.0111.
5-Iodo-4-p-tolylpyrrolo[1,2-a]quinoline (5b). The product was
1
obtained as a brown solid: mp 122À127 °C; H NMR {400 MHz,
(CD3)2SO} δ 8.35À8.34 (m, 1H), 8.24 (d, J = 8.2 Hz, 1H), 8.05 (d,
J = 8.2 Hz, 1H), 7.64 (t, J = 6.8 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.32 (d,
J = 7.8 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 6.68 (t, J = 3.7 Hz, 1H),
5.89À5.88 (m, 1H), 2.39 (s, 3H); 13C NMR {100 MHz, (CD3)2SO} δ
139.1, 138.7, 137.4, 133.5, 132.1, 131.3, 129.0, 124.9, 124.0, 115.1, 114.2,
113.2, 104.7, 93.2, 20.9; HRMS m/z calcd for C19H14IN 383.0171,
found 383.0177.
Compound 5b crystallized in the triclinic crystal system with space
group P1. The single-crystal X-ray data were collected using graphite-
monochromated Mo KR radiation (λ = 0.71073 Å). The structures were
solved using SIR-92 and refined by the full matrix least-squares tech-
nique on F2 using the SHELXL-9726 program within the WinGX v
1.80.05 software package. All hydrogen atoms were fixed at the cal-
culated positions with isotropic thermal parameters, and all non-hydro-
gen atoms were refined anisotropically. Crystal data for 5b: C19H14IN,
M = 383.21, triclinic, space group P1, a = 9.435(8) Å, b = 9.792(8) Å, c =
9.984(8) Å, R = 110.441(8)°, β = 114.906(8)°, γ = 93.239(7)°, V =
761.22(11) Å3, Z = 2, T = 150 K, dcalcd = 1.672 Mg/m3, R(int) = 0.0269,
R1 = 0.0353, wR2 = 0.0913 [I > 2σ(I)], R1 = 0.0380, wR2 = 0.0928 (all
data), GOF = 1.062. For further details on the crystal structure of com-
pound 5b, see the CIF file (Supporting Information).
4-(4-Ethylphenyl)-5-iodopyrrolo[1,2-a]quinoline (5c). The product
was obtained as a brown solid: mp 103À106 °C; 1H NMR (300 MHz,
CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.86À7.79 (m, 2H), 7.54À7.49 (m,
1H), 7.39À7.22 (m, 5H), 6.68À6.66 (m, 1H), 6.07À6.06 (m, 1H), 2.76
(q, J = 7.5 Hz, 2H), 1.32 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 144.1, 139.6, 139.2, 134.4, 132.4, 132.3, 129.2, 128.5, 127.7, 124.8,
124.4, 114.0, 112.9, 112.5, 105.1, 93.3, 28.7, 15.3; HRMS m/z calcd for
C20H16IN 397.0327, found 397.0334.
4-(4-Butylphenyl)-5-iodopyrrolo[1,2-a]quinoline (5d). The product
1
was obtained as a gray solid: mp 80À81 °C; H NMR {400 MHz,
(CD3)2SO} δ 8.33 (s, 1H), 8.23 (d, J = 8.2 Hz, 1H), 8.05 (d, J = 10.5 Hz,
1H), 7.64 (t, J= 7.8 Hz, 1H), 7.47 (t, J= 8.2 Hz, 1H), 7.33 (d, J= 6.8 Hz, 2H),
7.23 (d, J= 5.9 Hz, 2H), 6.68 (t, J= 4.1 Hz, 1H), 5.88 (d, J= 4.1 Hz, 1H), 2.66
(t, J= 8.2 Hz, 2H), 1.62 (p, J= 6.8 Hz, 2H), 1.35 (st, J= 8.2 Hz, 2H), 0.91 (t, J
= 8.2 Hz, 3H); 13C NMR {100 MHz, (CD3)2SO} δ 142.3, 139.1, 138.5,
133.6, 131.9, 131.3, 129.1, 128.9, 128.2, 124.8, 124.0, 114.9, 114.2, 113.0,
5-Iodo-4-(thiophene-3-yl)pyrrolo[1,2-a]quinoline (5k). The pro-
duct was obtained as a brown solid: mp 127À130 °C; 1H NMR {400
MHz, (CD3)2SO} δ 8.35À8.34 (m, 1H), 8.24 (d, J = 8.1 Hz, 1H), 8.05
(dd, J = 1.4, 8.0 Hz, 1H), 7.72À7.62 (m, 3H), 7.47 (t, J = 7.3 Hz, 1H),
7.21À7.19 (m, 1H), 6.71 (t, J = 7.3 Hz, 1H), 6.04À6.03 (m, 1H); 13C
NMR {100 MHz, (CD3)2SO} δ 141.2, 134.2, 133.7, 131.9, 131.0, 129.3,
5680
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128.7, 126.0, 125.5, 124.9, 123.9, 115.0, 114.3, 113.1, 104.6, 93.4; HRMS
m/z calcd for C16H10INS 374.9579, found 374.9568.
(dd, J = 1.5, 8.1 Hz, 1H), 6.03 (t, J = 2.2 Hz, 2H), 5.40 (s, 2H); 13C NMR
{100 MHz, (CD3)2SO} δ 158.5, 152.3, 138.8, 133.7, 131.5, 129.92,
129.80, 127.2, 125.5, 125.0, 121.6, 121.2, 115.8, 115.1, 109.3, 103.2, 73.8;
HRMS m/z calcd for C19H14INO 399.0120, found 399.0133.
5-Iodo-7-methyl-6-phenylindolo[1,2-a]quinoline (6a). The product
was obtained as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 8.45À
8.42 (m, 2H), 8.14 (d, J = 7.8 Hz, 1H), 7.77 (d, J = 7.2 Hz, 1H), 7.60 (t,
J = 6.6 Hz, 1H), 7.50À7.19 (m, 7H), 7.04 (d, J = 4.5 Hz, 1H), 1.76 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 143.6, 136.1, 134.6, 131.5, 129.5,
129.3, 125.7, 124.9, 123.2, 122.9, 121.8, 119.7, 115.1, 114.2, 106.8, 9.4;
HRMS m/z calcd for C23H16IN 433.0327, found 433.0332.
5-Iodo-7-methyl-6-p-tolylindolo[1,2-a]quinoline (6b). The product
was obtained as a yellow solid: mp 150À152 °C; 1H NMR {400 MHz,
(CD3)2SO} δ 8.59 (t, J = 8.8 Hz, 2H), 8.10 (dd, J = 1.5, 8.1 Hz, 1H), 7.75
(d, J = 7.3 Hz, 1H), 7.72À7.67 (m, 1H), 7.48À7.35 (m, 5H), 7.18 (d, J =
8.1 Hz, 2H), 2.43 (s, 3H), 1.56 (s, 3H); 13C NMR {100 MHz,
(CD3)2SO} δ 140.5, 139.7, 137.6, 135.0, 134.0, 131.17, 131.08, 130.5,
130.1, 129.4, 129.1, 124.0, 123.7, 123.3, 121.9, 119.5, 115.3, 114.4, 106.0,
101.6, 21.0, 9.8; HRMS m/z calcd for C24H18IN 447.0483, found
447.0498.
5-Iodo-4-(phenanthren-9-yl)pyrrolo[1,2-a]quinoline (5l). The pro-
duct was obtained as a yellow solid: mp 208À210 °C; 1H NMR
{400 MHz, (CD3)2SO + CDCl3} δ 7.98 (t, J = 8.4 Hz, 2H), 7.34À
7.24 (m, 3H), 7.10 (d, J = 7.3 Hz, 1H), 6.89À6.86 (m, 2H), 6.82À6.77
(m, 3H), 6.69 (d, J = 8.1 Hz, 1H), 6.62À6.56 (m, 2H), 5.73 (t, J = 2.9 Hz,
1H), 4.94 (dd, J = 1.5, 3.7 Hz, 1H); 13C NMR {100 MHz, (CD3)2SO +
CDCl3} δ 136.5, 135.2, 131.9, 130.7, 130.0, 129.5, 128.5, 128.3, 127.8,
127.5, 127.1, 126.1, 125.5 125.2, 125.1, 124.2, 122.9, 122.3, 121.3, 120.9,
113.1, 111.9, 111.4, 103.2, 93.3; HRMS m/z calcd for C26H16IN
469.0320, found 469.0327.
4-Butyl-5-iodopyrrolo[1,2-a]quinoline (5m). The product was ob-
tained as a gray oil: 1H NMR {400 MHz, (CD3)2SO} δ 7.46À7.35 (m,
3H), 7.21À7.13 (m, 1H), 6.90À6.87 (m, 2H), 6,59 (t, J = 2.2 Hz, 1H),
2.81À2.77 (m, 2H), 1.51À1.47 (m, 2H), 1.37À1.33 (m, 2H), 0.90 (t, J =
7.3 Hz, 3H); 13C NMR {100 MHz, (CD3)2SO} δ 141.6, 137.3, 130.5,
129.2, 127.1, 125.7, 121.6, 119.3, 109.2, 108.7, 97.2, 94.3, 48.7, 29.7, 20.9,
13.9; HRMS m/z calcd for C16H16IN 349.0327, found 349.0315.
4-tert-Butyl-5-iodopyrrolo[1,2-a]quinoline (5n). The product was
obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.34 (dd,
J = 1.5, 2.9 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 8.1 Hz, 1H),
7.55 (t, J = 8.1 Hz, 1H), 7.40 (t, J = 8.1 Hz, 1H), 6.76 (t, J = 8.4 Hz, 1H),
6,59 (dd, J = 1.5, 3.6 Hz, 1H), 1,16 (s, 9H); 13C NMR {100 MHz,
(CD3)2SO} δ 141.2, 135.6, 133.3, 129.1, 126.4, 124.7, 121.3, 117.2,
114.2, 108.9, 102.8, 100.3, 34.8, 30.2; HRMS m/z calcd for C16H16IN
349.0327, found 349.0333.
4-Cyclohexyl-5-iodopyrrolo[1,2-a]quinoline (5o). The product was
obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.27 (d, J =
2.2 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 7.4 Hz, 1H), 7.56 (t, J =
7.3 Hz, 1H), 7.42 (t, J = 7.3 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 6.77 (t, J =
2.9 Hz, 1H), 3.57À3.51 (m, 1H), 2.23 (m, 2H), 1.88À1.86 (m, 2H),
1.73À1.67 (m, 2H), 1.46À1.38 (m, 4H); 13C NMR {100 MHz,
(CD3)2SO} δ 139.9, 134.3, 131.7, 128.6, 127.9, 124.7, 114.7, 113.4,
112.6, 104.4, 94.4, 93.4, 52.7, 29.5, 26.7, 25.3; HRMS m/z calcd for
C18H18IN 375.0484, found 375.0491.
4-Cyclopentyl-5-iodopyrrolo[1,2-a]quinoline (5p). The product was
obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.28 (d, J =
2.9 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.04À8.02 (m,1H), 7.57À7.53 (m,
1H), 7.42À7.38 (m, 1H), 6.75 (t, J = 4.0 Hz, 1H), 6.59 (dd, J = 1.4, 3.6
Hz, 1H), 3.96À3.86 (m, 1H), 2.13À2.05 (m, 2H), 1.98À1.86 (m, 2H),
1.79À1.74 (m, 2H), 1.64À1.50 (m, 2H); 13C NMR {100 MHz,
(CD3)2SO} δ 138.8, 134.2, 131.9, 128.6, 127.7, 124.1, 114.8, 113.7,
112.7, 103.1, 94.8, 52.0, 30.0, 26.7; HRMS m/z calcd for C17H16IN
361.0327, found 361.0318.
6-(4-Ethylphenyl)-5-iodo-7-methylindolo[1,2-a]quinoline (6c). The
1
product was obtained as a yellow solid: mp 155À157 °C; H NMR
(300 MHz, CDCl3) δ 8.37 (dd, J = 8.4, 4.2 Hz, 2H), 8.09 (d, J = 7.8 Hz,
1H), 7.67 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.40À7.23 (m,
5H), 7.15 (t, J = 8.5 Hz, 2H), 2.71 (q, J = 7.5 Hz, 2H), 1.55 (s, 3H), 1.27
(t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 144.5, 141.2, 140.3,
135.9, 134.5, 131.9, 131.1, 129.6, 129.2, 127.9, 124.8, 123.1, 122.8, 121.6,
119.6, 115.0, 114.1, 106.9, 101.2, 28.8, 15.5, 9.8; HRMS m/z calcd for
C25H20IN 461.0640, found 461.0631.
6-(4-Butylphenyl)-5-iodo-7-methylindolo[1,2-a]quinoline (6d). The
1
product was obtained as a yellow solid: mp 144À147 °C; H NMR
(300 MHz, CDCl3) δ 8.46À8.39 (m, 2H), 8.15 (d, J = 7.8 Hz, 1H), 7.73
(d, J = 7.5 Hz, 1H), 7.60À7.55 (m,1H), 7.46À7.28 (m, 5H), 7.28À7.17
(m, 2H), 2.74 (t, J = 7.5 Hz, 2H), 1.75À1.68 (m, 2H), 1.62 (s, 3H),
1.47À1.35 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 143.0, 141.1, 140.3, 135.9, 134.4, 131.8, 131.1, 129.5, 129.1,
128.4, 124.8, 123.1, 122.8, 121.6, 119.5, 115.0, 114.1, 106.9, 101.1, 35.5,
33.5, 22.3,14.9, 9.8; HRMS m/z calcd for C27H24IN 489.0953, found
489.0941.
6-(4-tert-Butylphenyl)-5-iodo-7-methylindolo[1,2-a]quinoline (6e).
The product was obtained as a yellow solid: mp 192À194 °C; 1H NMR
(300 MHz, CDCl3) δ 8.47À8.40 (m, 2H), 8.16 (d, J = 7.8 Hz, 1H), 7.73
(d, J = 7.8 Hz, 1H), 7.61À7.50 (m, 3H), 7.46À7.29 (m, 3H), 7.24À7.19
(m, 2H), 1.60 (s, 3H), 1.42 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
151.4, 140.8, 140.3, 135.9, 134.4, 131.9, 131.1, 129.2, 125.2, 124.8, 123.1,
122.8, 121.6, 119.6, 115.1, 114.8, 106.9, 101.9, 101.0, 34.7, 31.4, 9.7;
HRMS m/z calcd for C27H24IN 489.0953, found 489.0966.
4-Cyclopropyl-5-iodopyrrolo[1,2-a]quinoline (5q). The product was
obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.22À8.21
(m, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.99 (dd, J = 1.4, 8.0 Hz, 1H),
7.55À7.51 (m, 1H), 7.39À7.36 (m, 1H), 6.75À6.71 (m, 2H), 1.98À1.91
(m, 1H), 1.21À1.18 (m, 4H); 13C NMR {100 MHz, (CD3)2SO} δ 136.1
132.9, 131.8, 131.5, 128.9, 124.8, 124.2, 114.9, 114.0, 112.8, 103.0, 96.1,
19.8, 9.8; HRMS m/z calcd for C15H12IN 333.0014, found 333.0022.
(5-Iodopyrrolo[1,2-a]quinolin-4-yl)methanol (5r). The product was
obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ 8.29 (t, J =
2.2 Hz, 1H), 8.20 (d, J = 2.2 Hz, 1H), 8.05 (dd, J = 1.5, 8.1 Hz, 1H), 7.61
(td, J = 1.5, 7.3 Hz, 1H), 7.42 (t, J = 7.3 Hz, 1H), 6.90 (d, J = 2.2 Hz, 1H),
6.77 (t, J = 2.9 Hz, 1H), 4.87 (s, 2H), 3.74 (br s, 1H); 13C NMR {100
MHz, (CD3)2SO} δ 140.8, 137.1, 130.4, 129.7, 126.9, 125.5, 121.6,
112.1, 109.5, 103.4, 92.8, 73.0; HRMS m/z calcd for C13H10INO
322.9807, found 322.9801.
5-Iodo-6-(4-methoxyphenyl)-7-methylindolo[1,2-a]quinoline (6f).
1
The product was obtained as a yellow solid: mp 156À158 °C; H
NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.6 Hz, 1H), 8.44 (d, J = 8.5 Hz,
1H), 8.17 (dd, J = 6.0, 1.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.60 (t, J =
7.2 Hz, 1H), 7.46 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.33 (t, J =
7.8 Hz, 1H), 7.22 (t, J = 7.2 Hz, 2H), 7.06 (t, J = 8.2 Hz, 2H), 3.91 (s,
3H), 1.69 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.7, 140.1, 136.7,
136.2, 134.7, 132.3, 132.1, 131.3, 131.1, 129.4, 125.0, 123.4, 123.1, 121.8,
119.8, 115.2, 114.3, 114.0, 107.1, 102.1, 55.5, 10.4; HRMS m/z calcd for
C24H18INO 463.0433, found 463.0448.
Compound 6f crystallized with twin structures in the triclinic crystal
system with space group P1. The single-crystal X-ray data were collected
using graphite-monochromated Mo KR radiation (λ = 0.71073 Å). The
structures were solved using SIR-92 and refined by the full matrix least-
squares technique on F2 using the SHELXL-97 program within the
WinGX v 1.80.05 software package. All hydrogen atoms were fixed at
the calculated positions with isotropic thermal parameters, and all
5-Iodo-4-(phenoxymethyl)pyrrolo[1,2-a]quinoline (5s). The pro-
duct was obtained as a brown oil: 1H NMR {400 MHz, (CD3)2SO} δ
7.48À7.44 (m, 2H), 7.33À7.29 (m, 1H), 7.25À7.23 (m, 1H),
7.13À7.06 (m, 2H), 6.98À6.94 (m, 1H), 6.84À6.78 (m, 2H), 6.42
5681
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ARTICLE
non-hydrogen atoms were refined anisotropically. Crystal data for 6f:
C24H18INO, M = 463.29, triclinic, space group P1, a = 10.733(5) Å,
b = 11.104(5) Å, c = 18.129(5) Å, R = 89.215(5)°, β = 81.700(5)°, γ =
61.836(5)°, V = 1881.2(13) Å3, Z = 4, T = 296 K, dcalcd = 1.636 Mg/m3,
R(int) = 0.0325, R1 = 0.0523, wR2 = 0.1219 [I > 2σ(I)], R1 = 0.0627,
wR2 = 0.1271 (all data), GOF = 1.058. For further details on the crystal
structure of compound 6f, see the CIF file (Supporting Information).
4-(5-Iodo-7-methylindolo[1,2-a]quinolin-6-yl)-N,N-dimethylani-
line (6g). The product was obtained as a yellow solid: mp 158À160 °C;
1H NMR (400 MHz, CDCl3) δ 8.46 (dd, J = 8.4, 6.8 Hz, 2H), 8.17 (dd,
J = 6.8, 1.2 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.59 (dt, J = 6.4, 1.2 Hz,
1H), 7.45 (t, J = 7.2 Hz, 1H), 7.35 (d, J = 6.4 Hz, 1H), 7.31À7.27 (m,
1H), 7.16À7.13 (m, 2H), 6.86 (d, J = 8.8 Hz, 2H), 3.08 (s, 6H), 1.75 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 150.2, 140.6, 136.0, 135.4, 134.5,
131.1, 130.4, 129.0, 126.8, 126.6, 123.1, 122.7, 121.8, 119.9, 118.8, 115.0,
114.1, 111.8, 107.1, 40.5, 10.2; HRMS m/z calcd for C25H21IN2
476.0749, found 476.0737.
5-Iodo-7-methyl-6-m-tolylindolo[1,2-a]quinoline (6h). The pro-
duct was obtained as a yellow solid: mp 118À120 °C; 1H NMR (300
MHz, CDCl3) δ 8.49À8.42 (m, 2H), 8.17 (d, J = 7.8 Hz, 1H), 7.75 (d,
J = 7.8 Hz, 1H), 7.63À7.58 (m, 1H), 7.48À7.31 (m, 5H), 7.12À7.10 (m,
2H), 2.44 (s, 3H), 1.64 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 143.7,
140.2, 138.1, 135.9, 134.4, 131.8, 131.1, 130.3, 129.2, 128.3, 126.8, 124.7,
123.1, 122.8, 121.6, 119.5, 115.0, 114.1, 106.8, 100.8, 21.5, 9.9; HRMS
m/z calcd for C24H18IN 447.0484, found 447.0496.
130.0, 129.5, 125.3, 123.3, 122.8, 122.2, 121.2, 115.2, 114.1, 112.3, 105.5,
102.8, 54.6; HRMS m/z calcd for C23H16NIO 449.0276, found
449.0268.
4-(5-Iodoindolo[1,2-a]quinolin-6-yl)-N,N-dimethylaniline (6n). The
product was obtained as a yellow solid: mp 146À148 °C; 1H NMR {400
MHz, (CD3)2SO} δ 8.69À8.62 (m, 2H), 8.15 (d, J = 8.2 Hz, 1H),
7.80À7.71 (m, 2H), 7.49À7.41 (m, 2H), 7.37À7.33(m, 1H), 7.21 (d, J =
9.6 Hz, 2H), 6.87 (d, J = 9.2 Hz, 2H), 6.29 (s, 1H), 3.01 (s, 6H); 13
C
NMR {100 MHz, (CD3)2SO} δ 150.0, 139.4, 136.8, 134.2, 132.3, 130.0,
129.9, 129.5, 129.3, 124.4, 123.9, 122.7, 122.3, 121.4, 115.4, 114.6, 111.8,
100.6, 99.3, 40.1; HRMS m/z calcd for C24H19IN2 462.0593, found
462.0597.
6-(4-Methoxyphenyl)-7-methylindolo[1,2-a]quinoline(12).
The compound was synthesized by a reported procedure24 with a slight
modification. To a solution of 6f (0.25 mmol) in 5.0 mL of MeOH was
added CuI (10 mol %) followed by NaBH4 (1.5 equiv). The reaction
mixture was allowed to stir for 10 min at 25 °C under inert conditions.
The product was obtained as a yellow solid: mp 160À162 °C; 1H NMR
(400 MHz, CDCl3) δ 8.46 (d, J = 9.2 Hz, 1H), 8.38 (d, J = 8.7 Hz, 1H),
7.70 (d, J = 7.8 Hz, 1H), 7.51À7.44 (m, 2H), 7.38À7.29 (m, 4H), 7.18 (t,
J = 9.2 Hz, 1H), 6.92 (d, J = 5.0 Hz, 2H), 6.79 (s 1H), 3.81 (s, 3H), 1.89 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 136.4, 135.5, 132.3, 132.1,
131.3, 130.3, 128.3, 128.1, 124.2, 123.8, 122.5, 122.1, 121.2, 119.1, 115.0,
114.0, 113.5, 105.8, 55.3, 10.7; HRMS m/z calcd forC24H19NO 337.1467,
found 337.1455.
5-Iodo-7-methyl-6-o-tolylindolo[1,2-a]quinoline (6i). The product
was obtained as a yellow solid: mp 126À129 °C; 1H NMR (300 MHz,
CDCl3) δ 8.49 (d, J = 8.4 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.16 (d, J =
7.8 Hz, 1H), 7.75 (d, J = 7.5 Hz, 1H), 7.64À7.59 (m, 1H), 7.48À7.31
(m, 6H), 7.18 (d, J = 7.8 Hz, 1H), 2.13 (s, 3H), 1.62 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 143.2, 139.7, 136.6, 136.0, 134.4, 132.0, 131.8,
130.1, 129.8, 129.3, 128.7, 126.1, 124.6, 123.2, 122.9, 121.7, 119.6, 115.1,
114.2, 106.7, 19.4, 9.7; HRMS m/z calcd for C24H18IN 447.0484, found
447.0489.
5-Iodo-7-methyl-6-(thiophene-3-yl)indolo[1,2-a]quinoline (6j). The
product was obtained as a yellow oil: 1H NMR {400 MHz, (CD3)2SO} δ
8.58 (t, J = 8.2 Hz, 2H), 8.07 (d, J = 8.2 Hz, 1H), 7.79À7.75 (m, 2H),
7.71À7.67 (m, 1H), 7.56À7.51 (m, 2H), 7.47À7.35 (m, 2H), 7.14À7.11
(m,1H), 1.66 (s, 3H); 13C NMR {100 MHz, (CD3)2SO} δ 142.8, 135.4,
135.1, 134.0, 131.1, 130.5, 130.2, 129.2, 126.6, 125.3, 123.9, 123.7, 123.3,
121.9, 119.5, 115.3, 114.4, 110.1, 106.0, 102.2, 9.0; HRMS m/z calcd for
C21H14INS 438.9892, found 438.9905.
5-Iodo-6-p-tolylindolo[1,2-a]quinoline (6k). The product was ob-
tained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.75À7.62 (m,
3H), 7.53À7.47 (m, 1H), 7.38À7.14 (m, 5H), 7.04À6.73 (m, 2H),
6.70À6.68 (m, 1H), 6.39À6.32 (m, 1H), 2.28 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 140.2, 138.1, 135.9, 134.4, 131.8, 131.7, 131.1, 130.3,
129.2, 128.9, 128.3, 126.8, 124.7, 123.1, 122.8, 121.6, 119.5, 114.1, 106.8,
100.8, 21.6; HRMS m/z calcd for C23H16NI 433.0327, found 433.0319.
6-(4-Ethylphenyl)-5-iodoindolo[1,2-a]quinoline (6l). The product
was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.74À7.76
(m, 2H), 7.63À7.60 (m, 1H), 7.51À7.46 (m, 2H), 7.37À7.22 (m, 5H),
7.18À7.03 (m, 1H), 6.72À6.67 (m, 1H), 6.39À636 (m, 1H), 2.77 (q, J =
8.2 Hz, 2H), 1.31 (t, J = 8.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
139.9, 132.5 132.0, 131.6, 130.8, 130.5, 130.1, 129.3, 129.0, 128.4, 128.1,
127.5, 124.7, 124.0, 122.7, 122.0, 110.7, 110.2, 102.5, 96.6, 28.7, 15.3;
HRMS m/z calcd for C24H18IN 447.0484, found 447.0491.
6-(4-Methoxyphenyl)-12-methylindolo[2,1-a]isoquino-
line (13). The compound was synthesized by a reported procedure.18a
1
The product was obtained as a yellow solid: mp 156 °C; H NMR
(400 MHz, CDCl3) δ 8.42 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H),
7.52À7.39 (m, 5H), 7.27À7.24 (m, 1H), 7.05 (d, J = 8.4 Hz, 2H), 6.92
(t, J = 7.6 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 6.42 (s, 1H), 3.93 (s, 3H),
2.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.3, 138.3, 131.5, 130.5,
130.4, 130.2, 130.1, 129.3, 127.3, 126.7, 126.6, 126.2, 124.4, 121.0, 120.3,
118.1, 114.6, 114.4, 110.9, 105.5, 55.5, 11.9; HRMS m/z calcd for
C24H19NO 337.1467, found 337.1465.
5-(4-Methoxyphenyl)-4-p-tolylpyrrolo[1,2-a]quinoline(16).
The compound was synthesized by a reported procedure.20 The product
was obtainedasa paleyellowsolid: mp 160À164 °C; 1H NMR {400 MHz,
(CD3)2SO} δ 8.33À8.29 (m, 2H), 7.58À7.50 (m, 2H), 7.28À7.20 (m,
2H), 7.11À7.04 (m, 4H), 6.97 (d, J = 8.7 Hz, 1H), 6.83 (d, J = 8.6 Hz, 2H),
6.74À6.72 (m, 1H), 6.02À6.00 (m, 1H), 3.71 (s, 3H), 2.24 (s, 3H); 13C
NMR {100 MHz, (CD3)2SO} δ 158.8, 136.5, 135.0, 132.6, 131.7, 130.8,
130.2, 129.7, 129.0, 128.4, 127.8, 127.7, 124.8, 124.2, 115.2, 114.7, 114.1,
113.8, 113.3, 104.3, 55.6, 21.3; HRMS m/z calcd for C26H21NO 363.1623,
found 363.1626.
Methyl3-(4-(4-Butylphenyl)pyrrolo[1,2-a]quinolin-5-yl)acry-
late (17). The compound was synthesized by a reported procedure.21
The product was obtained as a yellow oil: 1H NMR {400 MHz,
(CD3)2SO} δ 8.37 (s, 1H), 8.30 (d, J = 8.2 Hz, 1H), 7.99 (d, J =
8.2 Hz, 1H), 7.68À7.59 (m, 2H), 7.43À7.39 (m, 1H), 7.30À7.22 (m,
4H), 6.74 (t, J = 3.4 Hz, 1H), 6.08 (d, J = 3.7 Hz, 1H), 5.93 (d, J = 16.4
Hz, 1H), 3.62 (s, 3H), 2.63 (t, J = 7.8 Hz, 2H), 1.59 (p, J = 7.3 Hz, 2H),
1.30 (st, J = 7.3 Hz, 2H), 0.89 (t, J = 7.3 Hz, 3H); 13C NMR {100 MHz,
(CD3)2SO} δ 166.1, 142.3, 140.6, 133.67, 132.8, 133.1, 130.6, 129.4,
128.3, 125.9, 124.2, 123.2, 121.4, 119.6, 115.3, 115.1, 113.65, 106.4, 51.4,
34.5, 32.9, 21.6, 13.8; HRMS m/z calcd for C26H25NO2 383.1885, found
383.1895.
5-Iodo-6-(4-methoxyphenyl)indolo[1,2-a]quinoline (6m). The pro-
duct was obtained as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.39
(d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.2 Hz, 1H), 7.67
(t, J = 7.6 Hz, 1H), 7.42 (m, 2H), 7.28 (d, J = Hz, 3H), 7.00 (dd, J = 2.0
Hz, 1H), 6.28 (dd, J = 6.4,2.0 Hz, 1H), 5.90 (dd, J = 5.6, 2.8 Hz, 1H),
5.53 (dd, J = 5.6, 2.8 Hz, 1H), 3.16 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.0, 139.7, 135.7, 135.3, 134.8, 134.3, 131.9, 131.6, 130.2,
12-Methyl-9,10-di-p-tolylbenzo[i]pyrrolo[1,2-f]phenanthr-
idine (18). The compound was synthesized by a reported procedure22
with a slight modification. To a solution of 5b (0.25 mmol) in 5.0 mL of
DMA were added PdCl2(PPh3)2 (10 mol %) and 1,2-di-p-tolylethyne
(1.3 equiv) followed by addition of 3.0 equiv of NaCl and 3.0 equiv of
KOAc. The reaction mixture was allowed to stir for 2 days at 110 °C
under inert conditions. The product was obtained as a yellow solid: mp
5682
dx.doi.org/10.1021/jo200638k |J. Org. Chem. 2011, 76, 5670–5684

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ARTICLE
246À248 °C; 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J = 8.8 Hz, 1H),
7.79 (d, J = 1.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.35À7.31 (m, 3H),
7.23À7.15 (m, 2H), 6.97 (d, J = 7.3 Hz, 2H), 6.90À6.88 (m, 2H),
6.86À6.82 (3H), 6.80À6.78 (m, 2H), 6,69 (t, J = 8.8 Hz, 1H), 2.33 (s,
3H), 2.26 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 139.5,
137.0, 136.52, 136.22, 136.01, 135.5, 133.3, 132.8, 131.3, 131.2, 130.1,
128.55, 128.45, 128.18, 127.2, 126.46, 126.28, 126.15, 124.9, 123.2,
122.32, 122.17, 115.0, 113.5, 112.8, 107.4, 29.7, 21.78, 21.27; HRMS
m/z calcd for C35H27N 461.2143, found 461.2149.
Hertog, H. J.; Van Eerden, J.; Harkema, S.; De Zeeuw, D. J. Org. Chem.
1987, 52, 4913.
(4) (a) Chandrasekhar, S. Advances in Liquid Crystals; Academic
Press: New York, 1982; Vol. 5, p 47. (b) Chandrasekhar, S.; Ranganath,
G. S. Rep. Prog. Phys. 1990, 53, 57. (c) Praefcke, K.; Kohne, B.; Singer, D.
Angew. Chem., Int. Ed. Engl. 1990, 29, 177.
(5) (a) Veber, D. F.; Strachan, R. G.; Bergstrand, S. J.; Holly, F. W.;
Homnick, C. F.; Hirschmann, R.; Torchiana, M. L.; Saperstein, R. J. Am.
Chem. Soc. 1976, 98, 2367. (b) Tsang, K. Y.; Diaz, H.; Graciani, N.;
Kelley, J. W. J. Am. Chem. Soc. 1994, 116, 3988.
4-(4-Methoxyphenyl)-5-(1H-pyrrol-1-yl)pyrrolo[1,2-a]quino-
line (19). The compound was synthesized by a reported procedure.18e,f
The product was obtained as a brown solid: mp 152À157 °C; 1H NMR
(400 MHz, CDCl3) δ 7.89À7.85 (m, 2H), 7.48À7.44 (m, 1H),
7.21À7.18 (m, 3H), 7.10À7.08 (m, 1H), 6.78À6.72 (m, 3H), 6.58 (d,
J = 2.2 Hz, 2H), 6.33 (dd, J = 1.4, 3.6 Hz, 1H), 6.11 (t, J = 2.2 Hz, 2H),
3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.1, 132.5, 131.2, 129.9,
128.2, 127.0, 126.4, 125.0, 124.1, 123.8, 123.2, 113.94, 113.48, 113.32,
113.02, 108.5, 105.7, 55.1; HRMS m/z calcd for C23H18N2O 338.1419,
found 338.1422.
4-(4-Methoxyphenyl)pyrrolo[1,2-a]quinoline (20). The synth-
esis procedure was the same as that for 12. The product was obtained as a
brown solid: mp 130À132 °C; 1H NMR (400 MHz, CDCl3) δ 7.85À7.80
(m, 2H), 7.59À7.57 (m, 3H), 7.42À7.38 (m, 1H), 7.26À7.22 (m, 1H),
6.94 (dd, J = 2.2, 6.6 Hz, 2H), 6.72 (t, J = 3.3 Hz, 2H), 6.54 (dd, J = 1.5, 3.7
Hz, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ159.5, 132.5, 132.3,
131.4, 131.0, 129.4, 128.5, 127.3, 124.3, 123.6, 117.5, 114.0, 113.9, 112.7,
112.5, 103.2, 55.3; HRMS m/z calcd for C19H15NO 273.1154, found
273.1149.
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’ ASSOCIATED CONTENT
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S
Supporting Information. X-ray crystallographic data of
b
compounds 5b and 6f in CIF format and copies of NMR spectra
of all compounds. This material is available free of charge via the
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: averma@acbr.du.ac.in.
’ ACKNOWLEDGMENT
We gratefully acknowledge the Department of Science and
Technology, New Delhi, and University of Delhi for financial
support. The University Science Instrumentation Centre, Uni-
versity of Delhi, is also gratefully acknowledged for providing the
instrumentation facilities. S.P.S., J.S., and V.R. are thankful to the
Council of Scientific and Industrial Research, New Delhi, India,
for a fellowship.
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