Site-selective electrophilic cyclization and subsequent ring-opening: A synthetic route to pyrrolo[1,2-a]quinolines and indolizines

Article abstract of DOI:10.1021/jo3015374

An efficient strategy for the synthesis of pyrrolo[1,2-a]quinolines and indolizines from pyranoquinolines via site-selective electrophilic cyclization and subsequent opening of pyran ring using silver/iodine under mild reaction conditions is described. Th

Full text of DOI:10.1021/jo3015374

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Article
Site-Selective Electrophilic Cyclization and Subsequent Ring Opening:
A Synthetic Route to Pyrrolo[1,2-a]quinolines and Indolizines
Trapti Aggarwal, Sonu Kumar, Devendra Kumar Dhaked,
Rakesh K. Tiwari, Prasad V. Bharatam, and Akhilesh K. Verma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo3015374 • Publication Date (Web): 05 Sep 2012
Downloaded from http://pubs.acs.org on September 10, 2012
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Site-Selective Electrophilic Cyclization and
Subsequent Ring Opening: A Synthetic Route to
Pyrrolo[1,2-a]quinolines and Indolizines
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Trapti Aggarwal,† Sonu Kumar,† Devendra K. Dhaked,‡ Rakesh K. Tiwari,†,§ Prasad V.
Bharatam‡ and Akhilesh K. Verma,†,*
† Synthetic Organic Chemistry Research Laboratory, Department of Chemistry, University of
Delhi, Delhi, 110007, India
‡ Department of Medicinal Chemistry, NIPER, Punjab (Mohali) -160062 India
§ Department of Biomedical & Pharmaceutical Sciences, University of Rhode Island, Kingston,
Rhode Island, USA
E-mail: averma@acbr.du.ac.in
O
Route A
OMe
O
Route B
OMe
O
R3
i. cat. Pd / base
i. cat. Pd / base
O
N
ii AgOTf (5 mol %)
or
R1
N
R2
ii AgOTf (5 mol %)
N
R2
R1
R1
I
3
2
R3
3 equiv I2
5
Y
R1 = H, OMe
6, 7
(Y = H)
8, 9 (Y = I)
R3
upto 92%
OMe
OMe
sonogashira
electrophilic
cyclization and
ring opening
electrophilic
cyclization
O
O
N
N
R2
R2 = Ph;
R3 = Aryl
R2 = Aryl/Alkyl;
R3 = Aryl
Ea = 31.31 kcal/mol
Ea= 9.01 kcal/mol
a
b
R3
4 R3
4
ABSTRACT: An efficient strategy for the synthesis of pyrrolo[1,2-a]quinolines and indolizines
from pyranoquinolines via site-selective electrophilic cyclization and subsequent opening of
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pyran ring using silver/iodine under mild reaction conditions is described. This approach
involves the preferential attack of the pyridyl nitrogen over aryl ring and leads to the formation
of 5-endo-dig cyclized products. Quantum chemical calculations between C-N (ΔEa = 9.01
kcal/mol) and C-C (ΔEa = 31.31 kcal/mol) bond formation were performed in order to rationalize
the observed site selectivity. Structure of the products were confirmed by the X-ray
crystallographic studies. Iodo-substituted compounds generated by the electrophilic
iodocyclization were further diversified via Pd-catalyzed cross-coupling reactions.
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INTRODUCTION
The simplicity, efficiency and generality of the transition-metal-catalyzed tandem reactions1
have led to its applications in the synthesis of a wide variety of heterocyclic/carbocyclic
compounds and natural products. Nitrogen-containing heterocycles and their analogues are
pharmaceutically important scaffolds.2 During the past decade, pharmacological prospectives of
the pyrrolo[1,2-a]quinolines3 and indolizines4 has been well recognized due to their potential
biological activity and presence in many natural alkaloids. Some of the pyrrole-fused
heterocycles, such as dihydroisoquinolines have shown in vivo activity against P388 leukemia5
(Figure 1). The nucleus of indolizine derivatives are associated with a wide range of biological
activities including anticancer,6 antibacterial,3a antifungal,7 anti- tubercular8 and anti-histaminic9,
cytotoxic and CNS depressant activity10 (Figure 1).
Although numerous methods are available for the synthesis of pyrrolo[1,2-a]quinoline11 and
indolizines,12 new strategies to synthesize these class of scaffolds with high molecular diversity
are highly in demand. Halogenated heterocyclic compounds serve as a useful platform for
increasing the molecular diversity.13 In this context, the reactions incorporating halogens like
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iodocyclization14,15 are highly valuable. The introduction of iodide functionality in the molecule
provide avenue for further synthetic elaboration.
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Figure 1. Selected examples of biologically relevant pyrrolo-quinolines and indolizines
In 2007, Gevergyon and co-workers16 reported the synthesis of pyrroloquinolines and
indolizines by the metal-catalysis (Scheme 1, eq 1). While, recently Kim and co-workers17
reported the synthesis of indolizines by 5-endo-dig iodocyclization (Scheme 1, eq 2). To the best
of our knowledge, cyclization followed by ring opening has not been explored. Herein, we
reported the synthesis of highly functionalized pyrrolo[1,2-a]quinoline and indolizines via
silver-catalyzed as well as iodine-mediated 5-endo-dig cyclization with successive ring opening
under mild reaction conditions (Scheme 2).
Scheme 1. Synthesis of Pyrroloquinolines and Indolizines
(i) Metal-catalyzed synthesis of pyrrolo[1,2-a]quinolines and indolizines by Gevorgyan and
co-workers
(ii) Iodine-mediated synthesis of indolizines by Kim and co-workers
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RESULTS AND DISCUSSION
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Previously, Larock and co-workers reported the synthesis of fused polycyclic compounds via
palladium-catalyzed annulations which involved the electrophilic cyclization through the CH
activation of adjacent aromatic carbon.18 As a part of our ongoing efforts in the synthesis of
heterocycles19 by electrophilic cyclization of alkynes,20 we hypothesized the synthesis of
polyheterocycles 5 from alkynyl pyranoquinoline 4 by C-C bond formation under proper reaction
conditions (Scheme 2, route A).
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Scheme 2. Design of Tandem Strategy for the Synthesis of Heterocycles 5_9
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Our initial studies showed that reaction failed to afford the designed heterocycle 5, however
a novel product 6a was isolated (Scheme 2, route B). The structure of the product 6a was
unambiguously established as pyrrolo[1,2-a]quinoline by the X-ray crystallographic analysis21
(See Supporting Information Figure S1). Efforts to synthesize 6a directly from 4-
iodopyranoquinoline 2a require high catalyst loading and afforded the product 6a in low yield.
The possible reason might be due to the formation of iodo reduced22 product. This developed
methodology provides heterocycles with two carbonyl groups, which could be useful for the
medicinal utility of the molecule.4e
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To identify the optimal conditions for the reaction, a number of reported catalysts for
cyclization such as Ag(I), Cu(I), Pd(II) and I2 along with several organic solvents were examined
in the reaction of 1-methoxy-3-phenyl-4-(phenylethynyl)-1H-pyrano[4,3-b]quinoline (4a) under
various conditions (Table 1). When 5 mol % of Pd(OAc)2 were used as catalyst in CH2Cl2, no
consumption of substrate 4a was observed after 5 h (Table 1, entry 1). Increasing the catalyst
loading from 5 to 10 mol % made no effect on the substrate 4a even after 10 h (entry 2).
PdCl2(PPh3)2 and CuI were also found ineffective for the reaction (entries 3 and 4). When Ag(I)
salts like AgOTf was used, surprisingly product 6a was obtained in 90% yield (entry 5).
Decreasing the catalyst loading from 10 to 5 mol % made no considerable effect on the yield of
product 6a and the reaction was completed in 3 h (entries 6 and 7). Decrease in the catalyst
loading from 5 to 2 mol % adversely effected the yield of the product 6a (entry 8). Longer
reaction time also lead to the incomplete conversion of 4a and afforded the product 6a in 55%
yield only (entry 9). From entries 9–13 in table 1 it is apparent that solvent has a significant
influence on the reaction. CH2Cl2 and CHCl3 were found suitable for this reaction, THF afforded
the product 6a in lower yield (entries 10 and 11), while no reaction was observed in protic
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solvents like EtOH and H2O (entries 12 and 13). Other silver-catalysts like AgOAc and AgNO3
were found effective and afforded the product 6a in 60 and 78% yields respectively (entries 14
and 15). After screening various metal-catalysts, Ag(I) catalyst was found to be most efficient to
carry out this transformation.
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Table 1. Optimization of the Reaction Conditionsa
yieldb
entry
1
solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
THF
catalyst
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
CuI
mol%
5
t (h)
5
6a
8a
-
00
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
10
10
10
10
5
10
10
10
5
00
00
00
90
90
90
45
55
86
75
00
00
60
3
4
5
AgOTf
6
AgOTf
5
7
AgOTf
AgOTf
5
3
8
2
3
9
AgOTf
2
5
10
11
AgOTf
5
3
AgOTf
5
3
12
13
EtOH
AgOTf
5
3
H2O
AgOTf
5
3
14
CH2Cl2
AgOAc
5
3
15
16
CH2Cl2
CH2Cl2
AgNO3
I2
5
3
3
78
-
-
10
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CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
I2
I2
I2
I2
1c
2c
3c
3c
3
3
-
-
-
-
45
70
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10
a Reactions were performed using 0.25 mmol of 4a, catalyst in 2.0 mL of solvent at
25 °C unless otherwise noted. b Isolated yield. c equiv.
After optimizing the reaction conditions with metal-catalysts, we next examined the
efficacy of iodine for this reaction. Use of catalytic amount of iodine was found ineffective
(entry 16); however 1.0 equivalent of iodine afforded the 2-iodopyrrolo[1,2-a]quinoline 8a in
45% yield (entry 17). With 2.0 equivalent of iodine, product 8a was obtained in 70% yield (entry
18); while 3.0 equivalent of iodine afforded the product 8a in 85% yield with in 3 h (entry 19). A
longer reaction time made no significant changes in the yield of product 8a (entry 20).
We then investigated the substrate scope of the developed chemistry (Table 2). The
substrate 4-alkynyl-pyrano[4,3-b]quinolines 4a–o and pyrano[4,3-b]pyridine 4p–t required for
examining the scope of the reaction were readily prepared by the Sonogashira coupling of the 4-
iodopyrano[4,3-b]quinolines 2a–j with terminal alkynes 3. The substrate 2a–j required for this
approach were readily prepared by electrophilic iodocyclization of ortho-alkynylaldehydes using
reported procedure (Scheme 3).15b-c
Scheme 3. Synthesis of 4-Iodopyrano[4,3-b]quinolines (2a–j) and 4-alkynyl-pyrano[4,3-
b]quinolines
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As shown in Table 2, the reaction was well tolerant towards a variety of R1, R2 and R3
substituents (entries 1–20). Substrates bearing aryl group at R2 afforded the desired product 6a–
o, 6l in good to excellent yields (entries 1–12, 15). However, aliphatic substituents afforded the
desired products 6m and 6n in lower yields and required longer reaction time (entries 13 and 14).
The substrates 4m–n with aliphatic substituents were unstable; therefore they were used directly
for the reaction without isolation. Alkynes bearing an electron-rich substituents at R3 provided
the desired products 6b–c, 6e–g, 6i–k in 82–92% yield (entries 2–3, 5–7, 9–11). However,
substrates 4h and 4l having n-alkyl substituted aryl group at R3 afforded the products 6h and 6l
in comparatively lower yields (entries 8 and 12). The presence of OMe group at R1 made no
significant effect on the yield of the desired product 6o (entry 15). To further examine the
generality of the developed chemistry, pyrano[4,3-b]pyridines 4p–t were allowed to react under
the optimized reaction conditions (entries 16–20). The electron-deficient aromatic ring of this
substrate afforded the corresponding indolizines 7a–e in 75–80% yields. No significant effect on
the yield of the product 7a was observed with substrate 4p having meta substituted aryl alkyne at
R3 (entry 16).
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Table 2. Scope of the Developed Tandem Strategy for the Synthesis of Pyrrolo[1,2-
a]quinolines 6a–i and Indolizines 7a–ca
entry
substrate
product
yieldb
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OMe
O
N
90
92
6a
6b
1
2
4a
Me
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4b
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4g
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4h
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4j
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85
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6k
4k
4l
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78c
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4n
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4p
4q
4r
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80
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a
Unless otherwise specified, all reactions were performed with alkynyl
pyranoquinoline 4 (0.25 mmol), AgOTf (5.0 mol %) in 2.0 mL of CH2Cl2 at 25 °C
for 3–4 h. b Isolated yields. c reactions for 7–8 h.
After obtaining successful results with Ag(I) catalyst, we have further extended the scope of
this chemistry by employing iodine as an electrophile. To our delight, this electrophilic
cyclization proceeded smoothly and afforded the iodo products 8a–j and 9a–b in good yields
(Table 3). Substrate with electron-rich substitutents afforded the corresponding products 8a–h, 8j
in 75–84% yields (entries 1–8, 10), while product 8i was obtained in 70% yield with alkyne 4n
bearing cyclohexyl group at R2 (entry 9). Iodo-indolizines 9a–b were obtained in 72–75% yields
using alkynes 4q and 4s (entries 11 and 12).
Table 3. Synthesis of Pyrrolo[1,2-a]quinolines 8a–j and Indolizines 9a–ba
entry
substrate
product
yieldb
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4n
4o
10
8j
11
12
4q
4s
9a
9b
70
72
a All reactions were performed with alkynyl pyranoquinoline 4 (0.25 mmol), I2 (3.0
equiv) in 2.0 mL of CH2Cl2 at 25 °C for 3–4 h. b Isolated yields.
The formation of the desired iodocyclized compounds 8a–j and 9a–b were confirmed by their
spectral data (1HNMR, CNMR and HRMS) and finally by the X-ray crystallographic data of
13
compound 9b21 (See supporting Information Figure S2).
To rationalize this tandem process, we proposed a plausible mechanism (Scheme 4).
Presumably, the Ag metal coordinates with the triple bond of alkyne 4, to form intermediate P,
similarly iodine forms iodonium intermediate P'. The formation of intermediate P and P'
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triggering the attack of pyridyl nitrogen on the triple bond which leads to the generation of
cationic species Q and Q' via intramolecular 5-endo-dig cyclization.16b The cationic species Q
and Q' then aromatize to form the oxonium intermediate R. Due to the instability of the
intermediate R, it immediately converts into a more stable intermediate S by opening of pyran
ring, which upon loss of the Me18c and MeI13f provided the product 6, 7 and 8, 9 respectively.
Loss of the Me group is thought to occur during the aqueous workup, but the actual path for this
step is unclear.
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Scheme 4. A Plausible Mechanism
4
I2
AgOTf
6,7
alkyne
OMe
O
OMe
O
activation
8,9
+
MeI
N
Ph
I
Me
O
N
Ph
P
Ag
I+
P'
R3
O
R3
electrophilic
cyclization
N
Ph
electrophilic
cyclization
S
R3
I
Ag/
OMe
OMe
ring
opening
O
O
N
Ph
N
Ph
cation
R3
Ag
stablization
by oxygen
OMe
O
R3
I
Q'
Q
N
Ph
R3
Ag/I
R
With above results, we investigated further structural elaboration of the iodo-substituted
pyrrolo[1,2-a]quinolines via palladium-catalyzed cross-coupling reactions. To this end,
compound 8a was functionalized by applying palladium-catalyzed Suzuki23 and Heck24 coupling
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reactions to afford the corresponding products 11 and 13 in 75% and 70% yields, respectively
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(Scheme 5).
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9
Scheme 5. Pd-Catalyzed Cross-Coupling Reactions of 8a
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O
O
1.2 equiv
Me
1.2 equiv
Me
N
O
O
MeO
B(OH)2
O
N
N
12
10
8a
5 mol % Pd(PPh3)2Cl2
K3PO4 (2.5 equiv),
DMF, 120 °C, 4 h
5 mol % Pd(PPh3)2Cl2
K2CO3 (2.5 equiv),
DMF:H2O, 80 °C, 2 h
Me
N
Me
Me
O
13
Me
11
OMe
COMPUTATIONAL STUDIES
In order to understand the site-selectivity for ring cyclization (Scheme 6) by C-C (path ′a′) or
N-C (path ′b′) bond formation, quantum chemical calculations have been performed on the
model system (4d; R2 = Ph, R3 = Ph).
Scheme 6. Possible Site-Selective Electrophilic Cyclization
The fate of this reaction depends on the pre-reaction complex (PRC; complex of 4 and
AgNO3), (Figure 2). In the formation of PRC 11.73 kcal/mol [in complexation of reactants
(REC) 4 and AgNO3] energy is released. PRC may lead to two kinds of products, based on the
attack of pyridine N (C-N bond formation) and/or phenyl CH (C-C bond formation). The 3D
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structures of PRC, transition states (TS-1 and TS-2) and the intermediates (INT-1 and INT-2)
on the reaction paths ′a′ and ′b′ respectively were obtained using B3LYP optimization. In PRC,
Ag metal is almost symmetrically attached to both alkynyl carbons (C1 and C2) but in the
transition states, it is preferably attached to the C2 atom. Therefore, this C2 adapts sp2 character,
leading to an increased proximity between C1 and pyridine N or CH.
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1.85 Å
INT‐1
TS‐1
C‐C bond formation
C2
C1
2.38 Å
2.34 Å
PRC
2.11 Å
INT‐2
TS‐2
C‐N bond formation
Figure 2. 3D Geometry (B3LYP/6-31+G(d)) of PRC, transition states (TS-1 and TS-2) and
intermediates (INT-1 and INT-2) (LanL2DZ basis set is used for Ag metal).
Figure 3 shows that the formation of INT-2 is exothermic by 7.70 kcal/mol with an energy
barrier of 9.01 kcal/mol. On the other hand, the energy barrier for the formation of INT-1 is
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larger by 22.30 kcal/mol and lead to an endothermic INT-1. This establishes that the formation
of a five membered ring through C-N bond formation is the preferred path as per thermodynamic
as well as kinetic controls.
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TS‐1
INT‐1
31.31
REC
C‐C interaction
C‐N‐interaction
TS‐2
9.01
0
0
2
4
6
8
10
‐5
PRC
INT‐2
‐10
Figure 3. Potential energy surface for PRC, transition states (TS-1 and TS-2) and intermediates
(INT-1 and INT-2) (B3LYP/6-31+(d)).
CONCLUSIONS
In summary, we have demonstrated the facile synthesis of substituted pyrrolo[1,2-a]quinolines
and indolizines via electrophilic cyclization followed by ring opening under mild reaction
conditions using silver catalyst as well as inexpensive iodine. This chemistry involved the
preferential nucleophilic attack of the pyridyl nitrogen over aryl ring onto the adjacent alkyne
carbon to form 5-endo-dig cyclized products. The formation of 5-endo-dig cyclized products by
the site-selective electrophilic cyclization was supported by the quantum chemical calculations
between C-C (ΔEa = 31.31 kcal/mol) and C-N (ΔEa = 9.01 kcal/mol) bond of the substrate 4d.
The structure of the products were confirmed by the X-ray crystallographic studies. The cyclized
products 8 and 9 embedded with iodo group could be a useful handle for further elaboration
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using palldium-catalyzed coupling reactions. From a synthetic point of view, the net
transformation involves a one-step conversion of simple, and readily available starting materials
into interesting class of heterocyclic compounds. This chemistry is expected to find application
in organic synthesis in general, and in the construction of a variety of compounds. Further
investigations of this synthetic protocol are under progress and will be reported in due course.
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EXPERIMENTAL PROCEDURES
1
General Method: H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in
CDCl3. Chemical shifts for carbons are reported in ppm from tetramethylsilane and are
referenced to the carbon resonance of the solvent. Data are reported as follows: chemical shift,
multiplicity (s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, dd = doublet of doublet),
coupling constants in Hertz, and integration. High-resolution mass spectra were recorded with
electrospray mass spectrometer. Crystal structure analysis was accomplished on single crystal X-
ray diffractometer. TLC analysis was performed on commercially prepared 60 F254 silica gel
plates and visualized by either UV irradiation or by staining with I2. All purchased chemicals
were used as received.
The starting material 2 were prepared by electrophilic iodocyclization using reported
procedure.15b-c The structure and purity of known starting materials 2a−b, 2d−g,15a−b,2h and 2j13e
were confirmed by comparison of their physical and spectral data (1H NMR and 13C NMR) with
those reported in literature.
3-(4-Butylphenyl)-4-iodo-1-methoxy-1H-pyrano[4,3-b]quinoline (2c). The product was
1
obtained as light brown crystals (423.9 mg, 90% yield): mp 78–80 °C; H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.90 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.66 (t, J = 8.8, 1H),
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7.59 (d, J = 8.0 Hz, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.21–7.18 (m, 2H), 6.16 (s, 1H), 3.65 (s, 3H),
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2.61 (t, J = 7.7 Hz, 2H), 1.60–1.54 (m, 2H), 1.35–1.29 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H); C
7
8
9
NMR (100 MHz, CDCl3) δ 157.8, 148.8, 148.0, 145.0, 134.1, 133.1, 130.2, 129.9, 129.4, 127.9,
127.5, 127.4, 126.3, 121.9, 100.4, 56.5, 35.6, 33.3, 22.4, 13.9; HRMS (ESI) calcd for
[C23H22INO2] requires [M]+ 471.0695, found [M]+ 471.0698.
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8-Iodo-5-methoxy-7-(p-tolyl)-5H-pyrano[4,3-b]pyridine (2i). The product was obtained as
1
semi-solid; H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 5.8 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H),
7.51(d, J = 7.3 Hz, 1H), 7.27 (s, 1H), 7.26–7.22 (m, 2H), 6.09 (s, 1H), 3.67 (s, 3H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 156.1, 150.7, 148.2, 139.9, 133.7, 133.3, 129.8, 128.6, 122.2,
99.9, 75.9, 56.1, 21.5; HRMS (ESI) calcd for [C16H14INO2] requires [M]+ 379.0069, found [M]+
379.0070.
General Procedure for the Synthesis of Alkynyl-pyrano[4,3-b]quinoline and Pyridine
4a–u. To a solution of 4-iodopyranoquinoline 1 (0.25 mmol) in DMF were added 5 mol% of
PdCl2(PPh3)2. The reaction vial was then sealed and flushed with nitrogen. Then 3.0 equiv of
DIPA and 1.2 equiv of alkyne were added. The reaction was then stirred at 80°C until TLC
revealed complete conversion of the starting material. The solution was allowed to cool and
diluted with H2O and then extracted with EtOAc. The combined organic layers were dried over
Na2SO4, concentrated, and purified by column chromatography to afford the corresponding
product. The structure and purity of known starting materials 4f−g15a were confirmed by
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comparison of their physical and spectral data (1H NMR and C NMR) with those reported in
literature.
1-Methoxy-4-(phenylethynyl)-3-(p-tolyl)-1H-pyrano[4,3-b]quinoline (4a). The product was
obtained as semi-solid (151.2 mg, 75% yield); 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.8 Hz,
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1H), 8.11 (d, J = 8.0 Hz, 2H), 7.99 (s, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.65 (td, J = 1.4 and 6.6 Hz,
1H), 7.51 (dd, J = 1.4 and 8.0 Hz, 2H), 7.41 (t, J = 8.0 Hz, 1H), 7.29–7.21 (m, 5H), 6.25 (s, 1H),
3.68 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.5, 149.1, 149.0, 140.7, 132.9,
131.4, 131.3, 130.0, 129.0, 128.7, 128.2, 127.7, 127.6, 127.0, 126.0, 124.2, 122.0, 100.3, 95.7,
85.0, 56.4, 21.5; HRMS (ESI) calcd for [C28H21NO2] requires [M]+ 403.1572, found [M]+
403.1575.
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1-Methoxy-4-((4-methoxyphenyl)ethynyl)-3-(p-tolyl)-1H-pyrano[4,3-b]quinoline (4b). The
1
product was obtained as a pale yellow solid (168.8 mg, 78 %): mp 80–82°C; H NMR (400
MHz, CDCl3) δ 8.24–8.18 (m, 3H), 8.06 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.72 (t, J = 8.0 Hz,
1H), 7.53–7.49 (m, 3H), 7.29 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 6.32 (s, 1H), 3.83 (s,
3H), 3.75 (s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4, 149.0, 140.7, 132.9, 131.4,
130.8, 130.0, 129.8, 129.0, 128.6, 127.6, 127.1, 126.0, 122.1, 116.5, 114.3, 113.8, 100.3, 95.9,
83.2, 56.4, 55.3, 21.6; HRMS (ESI) calcd for [C29H23NO3] requires [M]+ 433.1678, found
433.1679.
1-Methoxy-4-(thiophen-3-ylethynyl)-3-(p-tolyl)-1H-pyrano[4,3-b]quinoline (4c). The product
was obtained as dark brown solid (149.2 mg, 73% yield): mp 100–102°C; 1H NMR (400 MHz,
CDCl3) δ 8.22 (d, J = 8.8 Hz, 1H), 8.17 (d, J = 8.0 Hz, 2H), 8.07 (s, 1H), 7.82 (d, J = 8.0 Hz,
1H), 7.72 (t, J = 6.6 Hz, 1H), 7.54–7.53 (m, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.30–7.28 (m, 3H),
7.26–7.24 (m, 1H), 6.31 (s, 1H), 3.74 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
160.3, 148.9, 140.9, 133.1, 131.1, 130.2, 129.9, 129.8, 129.6, 129.0, 128.7, 128.1, 127.6, 127.0,
126.1, 124.9, 123.2, 122.6, 122.0, 100.3, 90.9, 84.0, 56.5, 21.6; HRMS (ESI) calcd for
[C26H19NO2S] requires [M]+ 409.1136, found [M]+ 409.1140.
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1-Methoxy-3-phenyl-4-(phenylethynyl)-1H-pyrano[4,3-b]quinoline (4d). The product was
obtained as semi-solid (136.1 mg, 70% yield); 1H NMR (400 MHz, CDCl3) 8.21–8.16 (m, 3H),
8.00 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.66 (td, J = 1.4 and 7.3 Hz, 1H), 7.48 (dd, J = 1.4 and 6.5
Hz, 2H), 7.43–7.41 (m, 4H), 7.29–7.23 (m, 3H), 6.27 (s, 1H), 3.69 (s, 3H); 13C NMR (100 MHz,
CDCl3) 160.0, 148.9, 148.7, 134.3, 132.9, 131.4, 130.3, 130.1, 129.9, 129.1, 128.2, 127.9,
127.8, 127.7, 126.2, 124.1, 121.9, 100.8, 100.5, 95.6, 84.7, 56.5; HRMS (ESI) calcd for
[C27H19NO2] requires [M]+ 389.1416, found [M]+ 389.1422.
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1-Methoxy-4-((4-methoxyphenyl)ethynyl)-3-phenyl-1H-pyrano[4,3-b]quinoline (4e). The
product was obtained as semi-solid (136.1 mg, 65% yield); 1H NMR (400 MHz, CDCl3) δ 8.22–
8.16 (m, 3H), 8.02 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.66 (td, J = 1.4 and 5.8 Hz, 1H), 7.45-7.40
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(m, 6H), 6.80 (dd, J = 6.7 and 2.0 Hz, 2H), 6.27 (s, 1H), 3.76 (s, 3H), 3.69 (s, 3H); C NMR
(100 MHz, CDCl3) δ 159.3, 149.0, 134.3, 133.0, 132.9, 130.2, 130.1, 129.8, 129.0, 127.9, 127.6,
127.1, 126.1, 122.0, 116.3, 113.8, 101.0, 100.4, 95.9, 83.2, 56.4, 55.3; HRMS (ESI) calcd for
[C28H21NO3] requires [M]+ 419.1521, found [M]+ 419.1522.
4-((4-Butylphenyl)ethynyl)-1-methoxy-3-phenyl-1H-pyrano[4,3-b]quinoline
(4h).
The
product was obtained as semi-solid (151.3 mg, 68% yield); 1H NMR (400 MHz, CDCl3) δ 8.27–
8.25 (m, 2H), 8.22 (d, J = 8.7 Hz, 1H), 8.06 (s, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.71 (td, J = 1.4
and 8.7 Hz, 1H), 7.50–7.45 (m, 6H), 7.14 (d, J = 8.0 Hz, 2H), 6.32 (s, 1H), 3.75 (s, 3H), 2.60 (t,
J = 7.6 Hz, 2H), 1.59–1.57 (m, 2H), 1.39–1.33 (m, 2H), 0.92 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 159.5, 149.1, 149.0, 142.9, 134.2, 132.9, 131.3, 130.2, 130.0, 129.8, 129.0,
128.3, 127.9, 127.6, 127.1, 126.1, 122.0, 121.2, 101.1, 100.4, 96.0, 84.0, 56.4, 35.6, 33.4, 22.3,
13.9; HRMS (ESI) calcd for [C31H27NO2] requires [M]+ 445.2042, found [M]+ 445.2046.
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6
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(4i). The product was obtained as semi-solid (154.7 mg, 65% yield); H NMR (400 MHz,
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CDCl3) 1H NMR (400 MHz, CDCl3) δ 8.24–8.20 (m, 3H), 8.03 (s, 1H), 7.78 (d, J = 8.0 Hz,
1H), 7.70 (t, J = 8.0 Hz, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.46 (t, J = 7.3 Hz, 1H ), 7.29 (d, J = 8.8
Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.28 (s, 1H), 3.80 (s, 3H), 3.72 (s, 3H) 2.68 (t, J = 7.32 Hz,
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2H), 1.68–1.60 (m, 2H), 1.43–1.33 (m, 2H), 0.94 (t, J = 7.32 Hz, 3H); C NMR (100 MHz,
CDCl3) δ 159.4, 149.2, 144.5, 132.9, 132.7, 131.5, 130.0, 129.7, 129.5, 129.0, 128.8, 128.1,
127.8, 127.6, 127.0, 126.0, 125.9, 122.0, 116.4, 113.9, 100.1, 95.7, 83.5, 56.4, 55.3, 35.6, 33.3,
22.3, 13.9; HRMS (ESI) calcd for [C32H29NO3] requires [M+H]+ 476.2225, found [M+H]+
476.2225.
3-(4-Butylphenyl)-1-methoxy-4-(thiophen-3-ylethynyl)-1H-pyrano[4,3-b]quinoline (4j). The
product was obtained as semi-solid (139.8 mg, 62% yield); 1H NMR (400 MHz, CDCl3) δ 8.17–
8.11 (m, 3H), 8.00 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.65 (td, J = 1.4 and 5.8 Hz, 1H), 7.45 (d, J
= 2.9 Hz, 1H), 7.41 (d, J = 7.3 Hz, 1H), 7.23–7.20 (m, 3H), 7.18 (s, 1H), 6.25 (s, 1H), 3.68 (s,
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3H), 2.61 (t, J = 6.9 Hz, 2H), 1.59–1.56 (m, 2H), 1.34–1.26 (m, 2H), 0.89–0.85 (m, 3H); C
NMR (100 MHz, CDCl3) δ 160.0, 149.1, 149.0, 145.7, 133.0, 131.5, 130.1, 129.9, 129.7, 129.0,
128.0, 127.6, 127.0, 126.1, 124.9, 123.2, 122.0, 114.1, 100.3, 91.0, 84.2, 56.4, 35.6, 33.3, 22.4,
13.9; HRMS (ESI) calcd for [C29H25NO2S] requires [M]+ 451.1606, found 451.1606.
3-(4-(tert-Butyl)phenyl)-1-methoxy-4-(p-tolylethynyl)-1H-pyrano[4,3-b]quinoline (4k). The
product was obtained as semi-solid (149.1 mg, 65% yield); 1H NMR (400 MHz, CDCl3) δ 8.34–
8.30 (m, 3H), 8.08 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.77 (t, J = 7.3 Hz, 1H), 7.59–7.56 (m, 4H),
7.52 (t, J = 6.7 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 6.35 (s, 1H), 3.79 (s, 3H), 2.42 (s, 3H), 1.44 (s,
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9H); C NMR (100 MHz, CDCl3) δ 159.5, 153.6, 149.1, 137.8, 132.9, 131.4, 131.2, 130.0,
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129.7, 129.1, 128.9, 128.6, 127.6, 127.0, 125.0, 124.8, 122.8, 121.1, 100.2, 96.0, 84.3, 56.4, 34.9,
31.1, 21.5; HRMS (ESI) calcd for [C32H29NO2] requires [M+H]+ 460.2276, found [M+H]+
460.2275.
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3-(4-(tert-Butyl)phenyl)-4-((4-butylphenyl)ethynyl)-1-methoxy-1H-pyrano[4,3-b]quinoline
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(4l). The product was obtained as semi-solid (162.8 mg, 65% yield); H NMR (400 MHz,
CDCl3) δ 8.34–8.29 (m, 3H), 8.08 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.76 (t, J = 8.0 Hz, 1H),
7.58–7.55 (m, 4H), 7.54–7.50 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 6.34 (s, 1H), 3.78 (s, 3H), 2.67
(t, J = 7.3 Hz, 2H), 1.70–1.63 (m, 2H), 1.44–1.43 (m, 9H), 1.41–1.39 (m, 2H), 0.99 (t, J = 8.08
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4, 153.6, 149.1, 142.8, 132.9, 131.4, 131.2, 130.0,
129.7, 128.8, 128.6, 128.4, 128.1, 127.6, 127.0, 125.9, 125.0, 122.0, 121.3, 100.1, 96.1, 84.3,
56.4, 35.6, 34.9, 33.3, 31.2, 22.3, 13.9; HRMS (ESI) calcd for [C35H35NO2] requires [M+H]+
502.2746, found [M+H]+ 502.2746.
3-(4-Ethylphenyl)-1,8-dimethoxy-4-(phenylethynyl)-1H-pyrano[4,3-b]quinoline (4o). The
product was obtained as a semi-solid (167.6 mg, 75% yield); 1H NMR (400 MHz, CDCl3) δ 8.14
(d, J = 8.0 Hz, 2H), 8.06 (d, J = 8.8 Hz, 1H), 7.87 (s, 1H), 7.50 (d, J = 6.5 Hz, 2H), 7.32–7.22
(m, 6H), 7.00 (d, J = 2.2 Hz, 1H), 6.21 (s, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 2.66 (q, J = 7.3 Hz,
2H), 1.21 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.2, 157.4, 146.8, 146.7, 144.7,
131.9, 131.4, 131.2, 130.3, 128.9, 128.0, 127.6, 127.3, 123.1, 122.9, 122.1, 105.3, 100.1, 99.6,
95.5, 84.6, 56.2, 55.3, 28.7, 15.1; HRMS (ESI) calcd for [C30H25NO3] requires [M+H]+
448.1912, found [M+H]+ 448.1913.
5-Methoxy-7-phenyl-8-(m-tolylethynyl)-5H-pyrano[4,3-b]pyridine (4p). The product was
obtained as a semi-solid (105.9 mg, 60% yield); 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 3.6
Hz, 1H), 8.22–8.20 (m, 2H), 7.59 (d, J = 5.8 Hz, 1H), 7.47–7.43 (m, 3H), 7.34–7.29 (m, 2H),
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7.24 (t, J = 6.6 Hz, 1H), 7.17 (t, J = 8.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 6.19 (s, 1H), 3.67 (s,
3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.5, 150.9, 148.8, 141.5, 137.7, 134.2,
133.5, 132.1, 130.1, 128.9, 128.7, 128.5, 128.0, 127.9, 125.0, 123.5, 122.0, 121.9, 99.9, 95.8,
84.0, 56.1, 21.2; HRMS (ESI) calcd for [C24H19NO2] requires [M]+ 353.1416, found [M]+
353.1420
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5-Methoxy-8-(phenylethynyl)-7-p-tolyl-5H-pyrano[4,3-b]pyridine (4q). The product was
obtained as a semi-solid (107.6 mg, 61% yield); 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 5.1
Hz, 1H), 8.07 (d, J = 8.0 Hz, 2H), 7.54–7.52 (m, 2H), 7.46–7.41 (m, 2H), 7.26–7.13 (m, 5H),
6.13 (s, 1H), 3.62 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.5, 151.1, 149.0,
140.4, 133.1, 131.4, 131.2, 128.8, 128.6, 128.4, 128.0, 127.98, 127.8, 127.7, 126.1, 124.0, 121.9,
121.6, 99.9, 99.4, 95.3, 84.8, 56.0, 21.3; HRMS (ESI): calcd for [C24H19NO2] requires [M]+
353.1416, found [M]+ 353.1426.
5-Methoxy-7-(4-methoxyphenyl)-8-(phenylethynyl)-5H-pyrano[4,3-b]pyridine (4r). The
product was obtained as a semi-solid (116.2 mg, 63% yield); 1H NMR (400 MHz, CDCl3) δ 8.69
(dd, J = 5.1 and 1.4 Hz, 1H), 8.15 (d, J = 8.8 Hz, 2H), 7.52 (dd, J = 7.3 and 1.4 Hz, 1H), 7.46
(dd, J = 8.0 and 1.4 Hz, 2H), 7.24–7.20 (m, 3H), 7.17–7.14 (m, 1H), 6.91 (d, J = 8.8 Hz, 2H),
6.12 (s, 1H), 3.81 (s, 3H), 3.62 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.2, 158.6, 151.0,
149.2, 133.2, 131.5, 130.7, 128.1, 127.7, 126.3, 122.0, 121.5, 113.3, 99.9, 98.5, 95.3, 84.9, 56.1,
55.4; HRMS (ESI) calcd for [C24H19NO3] requires [M]+ 369.1365, found [M]+ 369.1368.
5-Methoxy-7-(4-methoxyphenyl)-8-(p-tolylethynyl)-5H-pyrano[4,3-b]pyridine (4s). The
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product was obtained as a a semi-solid (124.4 mg, 65% yield); H NMR (400 MHz, CDCl3) δ
8.73 (dd, J = 2.2 and 5.1 Hz, 1H), 8.21 (dd, J = 2.2 and 6.5 Hz, 2H), 7.56 (dd, J = 1.4 and 7.3 Hz,
1H), 7.41 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 5.1 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.7
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Hz, 2H), 6.16 (s, 1H), 3.85 (s, 3H), 3.66 (s, 3H), 2.32 (s, 3H); C NMR (100 MHz, CDCl3) δ
161.0, 158.0, 151.1, 149.3, 137.7, 133.1, 131.3, 130.6, 128.9, 126.6, 121.9, 121.4, 121.0, 113.3,
99.9, 98.8, 95.4, 84.2, 56.0, 55.3, 21.5; HRMS (ESI) calcd for [C25H21NO3] requires [M]+
383.1521, found [M]+ 383.1524.
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5-Methoxy-7-(4-methoxyphenyl)-8-(thiophen-3-ylethynyl)-5H-pyrano[4,3-b]pyridine (4t).
The product was obtained as a semi-solid (112.5 mg, 60% yield); 1H NMR (400 MHz, CDCl3) δ
8.68 (dd, J = 1.4 and 5.1, 1H), 8.13 (dd, J = 2.2 and 6.6, 2H), 7.53–7.50 (m, 2H), 7.42 (d, J = 2.9
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Hz, 1H), 7.19–7.12 (m, 2H), 6.91 (d, J = 8.7, 2H), 6.12 (s, 1H), 3.80 (s, 3H), 3.62 (s, 3H); C
NMR (100 MHz, CDCl3) δ 161.0, 158.2, 151.1, 149.1, 133.1, 130.5, 129.9, 129.4, 129.2, 128.0,
127.7, 126.5, 124.8, 123.0, 121.8, 121.5, 113.3, 99.9, 90.4, 84.2, 56.0, 55.3; HRMS (ESI) calcd
for [C22H17NO3S]+ requires [M]+ 375.0929, found 375.0923.
3-(4-Butylphenyl)-1-methoxy-4-(phenylethynyl)-1H-pyrano[4,3-b]quinoline
(4u).
The
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product was obtained as a semi-solid (160.2 mg, 72% yield); H NMR (400 MHz, CDCl3) δ
8.14-8.12 (m, 3H), 7.98 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.51 (d, J =
6.6 Hz, 2H), 7.41 (t, J = 8.0 Hz, 1H), 7.29-7.22 (m, 5H), 6.24 (s, 1H), 3.68 (s, 3H), 2.62 (d, J =
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7.7 Hz, 2H), 1.60–1.56 (m, 2H), 1.34–1.29 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H); C NMR (100
MHz, CDCl3) δ 160.2, 148.9, 148.6, 145.7, 133.2, 131.1, 130.2, 128.9, 128.0, 127.9, 127.62,
127.59, 126.9, 126.0, 123.9, 121.8, 100.0, 99.7, 95.5, 84.5, 56.3, 35.4, 33.2, 22.1, 13.7; HRMS
(ESI) calcd for [C31H27NO2]+ requires [M]+ 445.2042, found 445.2041.
General Procedure for the Synthesis of 3-Benzoyl-1-aryl Pyrrolo[1,2-a]quinoline-4-
carbaldehyde 6a–o: To a vial 4-alkynl pyranoquinoline 3 (0.25 mmol) and 5 mol% AgOTf was
added in DCM. The reaction vial was then sealed and stirred at room temperature until TLC
revealed complete conversion of the starting material. The solution was diluted with H2O and
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then extracted with EtOAc. The combined organic layers were dried over Na2SO4, concentrated,
and purified by column chromatography to afford the corresponding product.
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3-(4-Methylbenzoyl)-1-phenylpyrrolo[1,2-a]quinoline-4-carbaldehyde (6a). The product was
obtained as a yellow solid (87.5 mg, 90% yield): mp 150–152 °C; 1H NMR (400 MHz, CDCl3) δ
10.26 (s, 1H), 7.94–7.89 (m, 3H), 7.86 (dd, J = 1.4 and 6.6 Hz, 1H), 7.52–7.48 (m, 6H), 7.39 (td,
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J = 0.7 and 6.5 Hz, 1H), 7.32–7.28 (m, 3H), 6.97 (s, 1H), 2.44 (s, 3H); C NMR (100 MHz,
CDCl3) δ 191.7, 188.9, 143.0, 136.6, 134.7, 134.2, 131.0, 130.8, 130.0, 129.8, 129.4, 129.0,
128.9, 128.6, 128.2, 128.1, 125.0, 124.2, 120.3, 118.3, 116.8, 21.6; HRMS (ESI) calcd for
[C27H19NO2] requires [M]+ 389.1416, found [M]+ 389.1416.
1-(4-Methoxyphenyl)-3-(4-methylbenzoyl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6b). The
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product was obtained as yellow crystals (96.3 mg, 92% yield): mp 164–166 °C; H NMR (400
MHz, CDCl3) δ 10.18 (s,1H), 7.83 (d, J = 8.0 Hz, 3H), 7.77 (dd, J = 5.8 and 1.4 Hz, 1H), 7.49 (d,
J = 8.7 Hz, 1H), 7.33–7.29 (m, 3H), 7.25 (dd, J = 8.8 and 1.4 Hz, 1H), 7.24–7.20 (m, 2H), 6.94
(d, J = 8.8 Hz, 2H), 6.86 (s, 1H), 3.83 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
191.7, 189.0, 160.0, 142.9, 140.7, 136.7, 135.1, 132.9, 130.8, 130.0, 129.8, 128.6, 127.9, 127.6,
126.3, 126.0, 124.9, 122.0, 120.0, 118.0, 116.5, 114.3, 100.3, 55.4, 21.6; HRMS (ESI) calcd for
[C28H21NO3] requires [M]+ 419.1521, found [M]+ 419.1520.
3-(4-Methylbenzoyl)-1-(thiophen-3-yl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6c). The
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product was obtained as yellow crystals (84.9 mg, 86% yield): mp 180–182 °C; H NMR (400
MHz, CDCl3) δ 10.25 (s, 1H), 7.93 (s, 1H), 7.90–7.85 (m, 3H), 7.57 (d, J = 8.0 Hz, 1H), 7.50–
7.48 (m, 2H), 7.41–7.37 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.12 (dd, J = 5.1 and 1.4 Hz, 1H),
7.00 (s, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 191.4, 188.9, 143.4, 136.8, 135.1,
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134.2, 131.0, 130.8, 130.3, 129.8, 129.0, 128.8, 128.1, 126.6, 125.6, 125.1, 125.0, 124.2, 120.5,
117.6, 116.6, 21.6; HRMS (ESI) calcd for [C25H17NO2S] requires [M]+ 395.0980, found [M]+
395.0985.
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3-Benzoyl-1-phenylpyrrolo[1,2-a]quinoline-4-carbaldehyde (6d). The product was obtained
as a yellow solid (82.5 mg, 88% yield): mp 150–152 °C; 1H NMR (400 MHz, CDCl3) δ 10.23 (s,
1H), 7.93–7.89 (m, 3H), 7.80 (d, J = 7.3 Hz, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.45–7.40 (m, 8H),
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7.32 (t, J = 6.6 Hz, 1H), 7.24 (td, J = 1.4 and 8.8 Hz, 1H), 6.90 (s, 1H); C NMR (100 MHz,
CDCl3) δ 191.8, 188.9, 139.3, 134.8, 134.1, 132.2, 131.1, 130.8, 130.1, 129.6, 129.4, 128.9,
128.7, 128.3, 128.2, 125.0, 124.3, 120.4, 118.3, 116.6. HRMS (ESI) calcd for [C26H17NO2]
requires [M]+ 375.1259, found [M]+ 375.1261.
3-Benzoyl-1-(4-methoxyphenyl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6e). The product
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was obtained as a yellow solid (92.1 mg, 91% yield): mp 160–162 °C; H NMR (400 MHz,
CDCl3) δ 10.22 (s, 1H), 7.92 (d, J = 7.3 Hz, 2H), 7.86 (s, 1H), 7.80 (dd, J = 1.4 and 7.3 Hz, 1H),
7.52–7.48 (m, 2H), 7.44–7.40 (m, 2H), 7.34–7.30 (m, 3H), 7.26 (dd, J = 1.8 and 8.7 Hz, 1H),
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6.94 (dd, J = 2.2 and 6.6 Hz, 2H), 6.86 (s, 1H), 3.83 (s, 3H); C NMR (100 MHz, CDCl3) δ
191.8, 189.0, 159.9, 139.4, 135.0, 132.1, 131.0, 130.9, 130.8, 130.1, 129.6, 128.3, 128.2, 128.1,
126.4, 125.0, 124.3, 120.1, 118.1, 116.4, 114.3, 55.4; HRMS (ESI) calcd for [C27H19NO3]
requires [M]+ 405.1365, found [M]+ 405.1366.
3-Benzoyl-1-(p-tolyl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6f). The product was obtained
as yellow crystals (86.5 mg, 89% yield): mp 130–132 °C; 1H NMR (400 MHz, CDCl3) δ 10.3 (s,
1H), 7.98 (d, J = 7.3 Hz, 2H), 7.94 (m, 1H), 7.87 (d, J = 7.3 Hz, 1H), 7.58–7.56 (m, 2H), 7.50–
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7.47 (m, 2H), 7.41–7.34 (m, 3H), 7.32–7.28 (m, 3H), 6.94 (s, 1H), 2.46 (s, 3H); C NMR (100
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MHz, CDCl3) δ 191.8, 188.9, 139.3, 138.7, 134.9, 132.1, 131.2, 130.8, 130.0, 129.6, 129.4,
129.3, 128.2, 125.0, 124.9, 124.3, 120.3, 120.2, 118.1, 116.5, 21.5; HRMS (ESI) calcd for
[C27H19NO2] requires [M]+ 389.1416, found [M]+ 389.1417.
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3-Benzoyl-1-(thiophen-3-yl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6g). The product was
obtained as a orange solid (80.9 mg, 85% yield): mp 168–170 °C; 1H NMR (400 MHz, CDCl3) δ
10.21 (s, 1H), 7.92–7.88 (m, 3H), 7.80 (dd, J = 1.4 and 7.3 Hz, 1H), 7.52–7.48 (m, 2H), 7.44–
7.40 (m, 4H), 7.37–7.29 (m, 2H), 7.60 (dd, J = 1.4 and 4.4 Hz, 1H), 6.93 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 191.6, 188.9, 139.3, 135.0, 134.1, 132.2, 130.8, 130.4, 129.6, 128.8, 128.3,
128.1, 126.6, 125.7, 125.1, 125.0, 124.2, 120.6, 117.6, 116.3; HRMS (ESI) calcd for
[C24H15NO2S] requires [M]+ 381.0823, found [M]+ 381.0825.
3-Benzoyl-1-(4-butylphenyl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6h). The product was
obtained as a yellow solid (89.4 mg, 83% yield): mp 140–142 °C; 1H NMR (400 MHz, CDCl3) δ
10.22 (s, 1H), 7.90 (dd, J = 2.2 and 6.6 Hz, 2H), 7.86 (s, 1H), 7.78 (dd, J = 1.4 and 7.3 Hz, 1H),
7.50–7.45 (m, 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.32–7.29 (m, 3H), 7.24–7.20 (m, 3H), 6.87 (s, 1H),
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2.63 (t, J = 8.0 Hz, 2H), 1.64–1.54 (m, 2H), 1.36–1.31 (m, 2H), 0.89 (t, J = 7.3 Hz, 3H); C
NMR (100 MHz, CDCl3) δ 191.8, 189.0, 143.7, 139.4, 134.9, 132.1, 131.3, 131.2, 130.8, 130.0,
129.6, 129.3, 128.9, 128.3, 128.2, 128.1, 125.0, 124.3, 118.2, 116.4, 35.5, 33.5, 22.3, 13.9;
HRMS (ESI) calcd for [C30H25NO2] requires [M]+ 431.1885, found [M]+ 431.1892.
3-(4-Butylbenzoyl)-1-(4-methoxyphenyl)pyrrolo[1,2-a]quinoline-4-carbaldehyde (6i). The
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product was obtained as yellow crystals (94.5 mg, 82% yield): mp 170–172 °C; H NMR (400
MHz, CDCl3) δ 10.27 (s, 1H), 7.93–7.91 (m, 3H), 7.85 (d, J = 7.3 Hz, 1H), 7.56 (d, J = 8.7 Hz,
1H), 7.41–7.36 (m, 3H), 7.33–7.28 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 6.94 (s, 1H), 3.90 (s, 3H),
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