Facile access to functionalized indenes and fused quinolines by regioselective 5-: Enolexo -dig Michael addition and cyclization reactions

Article abstract of DOI:10.1039/c7ob02498c

Herein we report a facile approach to synthesise multi-substituted indenes and cyclopenta[b]quinolines under mild conditions. The reaction proceeds via Michael addition between commercially available cyanoacetate/malonic esters and α,β-unsaturated ketones. The synthetic methodology involves enolate mediated regio- and stereoselective intramolecular 5-enolexo-dig cyclization promoted by a catalytic base. The products stereoselectively form cis-isomers for indenes and trans-isomers for cyclopenta[b]quinolines, albeit with the presence of steric hindrance at a quaternary carbon substituted by active methylene compounds. The reaction pathway was investigated by isolating the reaction intermediate. This synthetic transformation was achieved with various aromatic and heteroaromatic Michael acceptors and the desired products were obtained in high to excellent yields. The reaction is scalable up to gram level with only 10 mol% of base.

Full text of DOI:10.1039/c7ob02498c

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Received 00th January
20xx,
A Facile Access to functionalized Indenes and Fused Quinolines by
Regioselective 5‐enolexo‐dig Michael Addition and Cyclization
Reaction
Tohasib Yusub Chaudhari,a Sandeep K. Ginotrab and Vibha Tandon*a, b
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Herein we reported a facile approach to multi‐substituted indenes and cyclopenta[b]quinolines under mild conditions. The
reaction proceeds via Michael addition between commercially available cyanoacetate/malonic esters and α,β‐unsaturated
ketones. The synthetic methodology involves enolate mediated regio‐ and stereoselective intramolecular 5‐enolexo‐dig
cyclization promoted by a catalytic base. The products formed stereoselectively cis in indenes and trans‐isomers for
cyclopenta[b]quinolines albeit presence of steric hindrance at a quaternary carbon substituted by active methylene
compounds. The reaction pathway was investigated by isolating the reaction intermediate. This synthetic transformation
was achieved with various aromatic and heteroaromatic Michael acceptors and desired products were obtained in high to
excellent yields. The reaction is scalable up to grams level with only 10 mol% of base.
Michael addition has an important role in C‐C and C‐N bond
forming reactions to achieve the complex, diversified
enantioselective structure. In 2015, O. Kwon18 (Scheme 1, eqn
Introduction
Indenes1 and fused quinolines2 are an important core of many
natural products and pharmaceutical drugs. These scaffolds
show anti‐HIV,3 anti‐cancer,4 antidiabetic,5 anti‐inflammatory
activity.6 Particularly, cyclopentane ring fused quinolines
showed inhibitory activity as AchE inhibitor implicated in
Alzheimer's7 disease and excellent MIC against M.
tuberculosis.8 These molecules are DNA intercalators and
inhibit the enzymatic activity of topoisomerase I/II resulting in
antitumor/anticancer agents9 (Figure 1). In view of the
importance of these scaffolds, various transformations have
been reported for its synthesis in past two decades.10 In
particular, Jie Wu11 (Scheme 1, eqn 1) and R. Sanz12 had made
enormous contributions to the synthesis of indenes by Michael
addition and cycloisomerization cascade reactions using o‐
(alkynyl)styrenes. Jan Paradies13 used metal free frustrated
Lewis pair catalyst to achieve 5‐endo‐dig cyclization. Radical‐
mediated cyclization by I. V. Alabugin via 5‐exo‐dig14a as well as
5‐exo‐trig14b pathway developed to synthesize indene which
would further recycle to 6‐endo‐trig by homoallylic ring
expansion.14c Subsequently, domino coupling and C‐H
functionalization by gold catalyst15 have also emerged as a
method for preparation of indene derivatives. Recently, X. Xu16
has demonstrated the synthesis of spiroindene derivatives
using isocyanide by cycloaddition/iodocyclization strategy. In
2016, A. K. Verma group achieved Iodo‐substituted indenes by
5‐endo‐dig cyclization using enediyne.17
2), D. H. Dethe19 and R. Balamurugan20 developed Michael
reaction to access the indene scaffolds.
Among previously reported strategies, radical annulation21
Friedländer
condensation,22
Povarov
reaction,23
photocyclization24 found to be an important tool for the
synthesis of fused quinolines.
Figure 1 Selected examples of indene and fused quinoline
containing natural compounds.
In 2016, L. Zhou25 employed visible light mediated radical
cyclization to assemble fused quinolines. Most recently, 2,3‐
disubstituted fused quinolines were synthesized via
ketenimine or carbodiimide using α‐diazo ketones.26 In the
continuation of our ongoing research towards the synthesis of
N‐heterocycles,27 we successfully achieved the synthesis of
highly functionalized indenes and fused quinolines by the
tandem Michael addition followed 5‐enolexo‐dig cyclization.
The previously presented methodologies to synthesize indenes
and fused quinoline involve either harsh reaction conditions
a. Special Centre for Molecular Medicine, Jawaharlal Nehru University
Delhi 110067 (India)
E‐mail: vtandon@mail.jnu.ac.in
b. Department of Chemistry, University of Delhi
Delhi 110067 (India).
Electronic Supplementary Information (ESI) available: Copies of 1H, 13C and HRMS
spectra of all synthesized compounds as PDF. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Previous Work
The first enolate mediated 5‐enolexo‐dig cyclization was
described by J. E. Baldwin et al.28 The required “favored attack
trajectories” for alkyne cyclization is well supported by
experimental and theoretical calculations.29 We observed
selectively only cis product in case of indene and trans product for
fused quinolines via regioselective 5‐enolexo‐dig cyclization. The
pendant aryl group moves towards the quaternary carbon albeit the
presence of steric hindrance which was confirmed by crystal
analysis.30
Jie wu et al (2008)
CO2R4
R5
R1
t-BuOK (1 equiv)
CH3CN, 25oC
R4
(1)
CO2R3
R2
N
N
H
CO2R4
CO2R3
R2
R1
O. Kwon et al (2015)
20 mol % PPh3
CH3CN, 82oC, then
CO2R3
CO2R4
CO2R3
(2)
R1
CO2R2
R1
CO2R4
I
10 mol % Pd(OAC)2
nBu4NOAc, NaHCO3
82 oC, 8 h
CO2R2
R3
5 O
Michael addition
Results and discussion
Present work
R1
R2
Preparation of starting materials: To achieve our target moieties
indenes and cyclopenta[b]quinolines, we synthesized 1 by standard
Sonogashira cross‐coupling reaction followed by Knoevenagel
condensation reaction to delivered o‐alkynylaromatic/heterocylic
chalcones 3a‐j in good to excellent yield (Scheme 2).
R
O
CO2R4
Ph
R3
O
R1
Het
5
R4
R5
Cs2CO3 (cat.)
O
R3
CH3CN, T°C
3-12 h
R2
3
4
5 O
R
Herein, we choose (E)‐1‐phenyl‐3‐(2‐(phenylethynyl)phenyl)prop‐
2‐en‐1‐one (3a) and methyl cyanoacetate 4a as a model substrate
to intrigue the optimized conditions (Table 1).
CO2R4
Ph
N
6
The different bases were screened to optimize the reaction
conditions. Initially, we used organic base DBU 0.5 equiv. and Lewis
acid AgNO3 (10 mol %) providing desired Michael adduct 5a in 62%
yield in 2 h at room temperature (Table 1, entry 1). The Similar
reaction was carried out without Lewis acid to achieve the
functionalized indene (entry 2). The use of strong base did not
improve the yield (entry 3‐5). The good yields were obtained with
use of carbonate bases such as Na2CO3 and K2CO3 (entry 6‐8), while
NaHCO3 delivered 63% yield (entry 9).
Scheme 1 Synthetic route to indenes and cyclopenta[b]quinolines.
or high loading of catalysts and bases. Therefore, we
developed a highly regiospecific and stereoselective 5‐enolexo‐
dig cyclization of the above compounds promoted by a
catalytic base in mild conditions.
Table 1 Reaction optimizations for Michael additiona,b
Entry
Base
Solvent
Time(h)
Yield
(%)c
1c
2
DBU (50 mol%)
DBU (50 mol%)
t‐BuOK (1 equiv)
NaOH (50 mol%)
NaH ( 1 equiv)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMA
2
2
62
62
20
65
68
79
80
78
63
84
85
84
73
3
0.5
3
4
5
1
6
K2CO3 (50 mol%)
K2CO3 (1 equiv)
Na2CO3 (1 equiv)
NaHCO3 (1 equiv)
Cs2CO3 (10 mol%)
Cs2CO3 (15 mol%)
Cs2CO3 (20 mol%)
Cs2CO3 (15 mol%)
10
8
7
8
7
9
10
3
9
10
11
12
3
Scheme
2 Synthetic route to o‐alkynylaromatic/heterocyclic
3
chalcones. Reaction condition: 1 (5 mmol), 2 (5 mmol), 10% NaOH
(1.5 mL), MeOH (15 mL) room temperature, 3‐24 h.
3
2 | J. Name., 2012, 00, 1‐3
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13
14
15
16
17
18
Cs2CO3 (15 mol%)
DMF
DMSO
THF
3
4
76
79
Cs2CO3 (15 mol%)
Cs2CO3 (15 mol%)
Cs2CO3 (15 mol%)
Cs2CO3 (15 mol%)
Li2CO3 (15 ml%)
6
60
Dioxane
DCE
4
46
3
N. R.
68%
CH3CN
2.5
a
b
Reaction condition: 3a (0.5 mmol), 4a (0.6 mmol), Isolated yield
based on 3a, c AgNO3 (10 mol %) used.
Interestingly, 15 mol% of Cs2CO3 produced indene 5a (entry 10) in
85% yield and changing the quantity of Cs2CO3 did not affect the
yield at all (entries 9 and 11). The same reaction in non‐protic
solvents such as DMA, DMF and DMSO gave 5a in 73‐79% yield
(entry 12‐14). The reaction in THF and Dioxane provided lower yield
(entry 15 and 16). But the reaction completely failed in DCE (entry
17). Further there was no improvement in the reaction yield in the
presence
of
Li2CO3
(entry
18).
Scheme 3 Substrate scope of Michael addition using different
chalcones and cyanoacetates for the synthesis of Indenes. Reaction
Condition: 3a‐k (0.5 mmol), 4a‐f (0.6 mmol), Cs2CO3 (15 mol %),
CH3CN (3 mL), 3 h, Isolated pure products yield.
The structure of 5a was confirmed by single crystal X‐ray
crystallographic analysis.30
The results of the optimized conditions (entry 10) encouraged us
to study the substrate scope of Michael addition, with respect to
α,β‐unsaturated ketone and sterically featured cyanoacetates. The
results are summarized in (Scheme 3). The aromatic chalcones
bearing halogen substituents (3b‐c) at para‐position of phenyl ring
proceed well with methyl cyanoacetate 4a to afford 5b and 5c in 85
and 87% yield respectively. However, the substrate 3d having 2, 4‐
dichloro substituent gave 5d in 72% yield. Whereas chalcones 3e
and 3f bearing electron donating groups gave 5e and 5f in excellent
yields respectively. The substrate 3g, containing fluoro substituent
at R1 position and electron donating groups such as methoxy group
at R1 and R2 position of phenyl ring 3h furnished 5g and 5h in 87 and
86% yield respectively. Interestingly, 5i and 5j were obtained in
good yield by reacting ethyl cyanoacetate with 2‐furan and 2‐
thienyl containing chalcones respectively.
Scheme 4 Substrate scope of Michael addition with heteroarenes
chalcones for cyclopenta[b]quinolines. Reaction conditions: 3l‐o (0.5
mmol), 4 (0.6 mmol), Cs2CO3 (15 mol %), CH3CN 3 mL, Isolated pure
products yield.
Similarly, with ethyl cyanoacetate products 5k‐q obtained in 70‐
92% yield. Furthermore, steric nature of cyanoacetate was carefully
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react with diverse o‐alkynylaromatic/heterocylic chalcones to yield
the products 7a‐h in good to excellent yields.
To investigate the reaction mechanism, we conducted a few
control experiments. We isolated the intermediate of reaction such
as Michael product 8 (Scheme 7 eqn 1). When this intermediate
subjected to standard conditions, it delivered the 5‐enolexo‐dig
studied. The present synthetic pathway is well tolerated up to C4
aliphatic chains, such as n‐propyl 4c and n‐butyl 4d delivered
expected product 5r and 5s in excellent yields. The sterically
hindered nucleophiles 4e and 4f also gave products 5t and 5u in
similar yields respectively. The indenes formed by 5‐enolexo‐dig
cyclization were selectively Z‐isomers.
Due to the diverse utility of cyclopenta[b]quinolines in medicinal cyclized product 7c in 80% yield (Scheme 6, eqn 2). Based on the
evidence from the control experiments and result and discussion
we proposed a plausible reaction mechanism (Scheme 8).
scaffolds, we evaluated the scope of quinolines based Michael
acceptor 3l‐o (Scheme 4). To our surprise, these substrates well
tolerated Michael addition cyclization cascade reactions. The
electron withdrawing as well as electron donating heteroarene
chalcones provides the product 6a‐6c in excellent yields.
Interestingly, chalcones 3n with substitution at alkyne with an
electron donating group delivered the desired transformation in
good yield. This Michael addition-cyclization reaction is feasible
with substrate 3o bearing 2-thienyl group as well. The E‐isomers
were formed with quinoline containing chalcones as substrate.
Scheme 7 Control experiment for elucidation of mechanisms.
Base abstracts a proton from the active methylene compound ‘A’
and generates enolate ‘B’, which subsequently attacks at the β‐
position of chalcone furnishing Michael addition product ‘D’.
Further removal of an active proton from the intermediates ‘D’
generates enolate ‘E’. The base could be involved in activation of
the alkyne.31 This enolate attacks the LUMO of alkyne by an obtuse
angle at a π*‐system29 which leads to 5‐enolexo‐dig cyclization gives
the intermediates ‘F’ which on protonation furnished the desired
product ‘G’. The nucleophilic attack onto alkynes is favoring the
trans‐addition which resulted in the Z‐isomers in case of indenes
and E‐isomers for fused quinolines.32
Scheme 5 Michael reaction at gram scale. Reaction conditions: 3e
(1gm scale), 4b (1.2 equiv.), Cs2CO3 (10 mol %), 3 h, Isolated pure
product yield.
To demonstrate the rationality of present methodology, we
conducted the reaction in gram scale (Scheme 5). The reaction
delivered desired Michael product 5p in 90% yield with the 10 mol%
of Cs2CO3.
Scheme 6 Substrate scope of Michael addition with Malonic esters.
Reaction condition: 3a‐o (0.5 mmol), 4 (0.6 mmol), Cs2CO3 (30 mol
%), CH3CN (3 ml), 50 °C, 12 h, Isolated products yield.
To Next, we elaborate the substrate scope with malonic esters
(Scheme 6). The dimethyl and diethyl malonate 4g and 4h smoothly
Scheme 8 Plausible reaction mechanism of Michael addition.
4 | J. Name., 2012, 00, 1‐3
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heat at 50 °C for 3 to 12 h. After completion of the reaction
indicated by TLC, it was diluted with 10 mL of sat. NH4Cl
solution (in case of malonic ester 10 mL of dilute HCl was
added). Extraction with ethyl acetate (2 x 50 mL) and distilled
water (2 x 10 mL) was carried out. Finally, a combined organic
layer was washed with brine solution and dried over
anhydrous Na2SO4 and concentrated under vacuum to yield
the crude product, which was purified by chromatography on
silica gel using ethyl acetate/hexane as the eluent to yield the
5a‐7h as desired products.
Conclusions
In summary, we have developed an expeditious, cost‐efficient
method for the synthesis of highly substituted indenes and
cyclopenta[b]quinolines
using
aromatic/heteroaromatic
chalcones as building blocks. The reaction was completed
using a catalytic amount of base in air using mild conditions.
The stereochemistry of products did not change in the
presence of different cations such as Na+ or K+ and at variable
temperatures. The exclusive 5‐enolexo‐dig cyclization of o‐
alkynyl aromatic α,β‐unsaturated ketones yielded highly
regioselective product. The stereochemically single products
were obtained suggesting kinetically controlled reactions
according to Baldwin’s rules. The mechanistic pathway of
reaction has been described by isolating the intermediate. The
presence of cyano and ester group will facilitate the further
synthetic elaboration of the above compounds to synthesize
complex scaffolds.
(E)‐1‐Phenyl‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐en‐1‐one (3a).
Yellow oil; (1.46 gm, 95% yield); 1H NMR (400 MHz, CDCl3) δ = 8.24
(d, J = 16.0 Hz, 1H), 8.1 (d, J = 7.4 Hz, 2H), 7.79‐7.76 (m, 1H), 7.67 ‐
7.51 (m, 5H), 7.46 (t, J = 7.8 Hz, 2H), 7.40‐7.35 ppm (m, 5H); 13C
NMR (100 MHz, CDCl3) δ = 191.4, 143.0, 138.1, 136.1, 132.9, 132.6,
131.6, 129.8, 128.6, 128.4, 128.3, 128.2, 126.7, 124.3, 124.1, 122.7,
95.7, 87.1 ppm; HRMS (ESI) m/z calcd for C23H16O (M+H)+ 309.1279,
found 309.1277.
Experimental section
General Information
(E)‐1‐(4‐Fluorophenyl)‐3‐(2‐(phenylethynyl) phenyl) prop‐2‐e‐1‐
1
one (3b). Pale yellow solid; (1.50 gm, 92% yield); mp 87‐ 88°C; H
The solvents used for reactions were dried and distilled before
use by standard methods. All the reagents used were
commercially available and used without further purification.
1H and 13C NMR of compounds were recorded on JEOL
spectrometer using 400 MHz and 100 MHz frequency
respectively. The HRMS (m/z) of synthesized compounds were
recorded on Mass Q‐TOF LC/MS mass spectrometer. Melting
points were measured using Buchi‐B‐540 instrument and are
uncorrected. For the monitoring and visualization of reactions,
TLC coated on silica gel plates (silica gel 60, F254) was used.
NMR (400 MHz, CDCl3) δ = 8.32 (d, J = 16.0Hz, 1H), 8.05‐8.09 (m,
2H), 7.76‐7.74 (m, 1H), 7.64‐7.59 (m, 2H), 7.54‐7.51 (m, 2H), 7.40‐
7.35 (m, 5H), 7.12 ppm (t, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ = 189.5, 165.5 (d, J = 252.6 Hz), 143.1, 135.9, 134.4, 132.9, 131.5,
131.1, 131.0, 129.9, 128.6 (d, J = 17.1 Hz), 128.4, 126.8, 124.3,
123.6, 122.6, 115.6 (d, J = 20.9 Hz), 95.8, 87.1 ppm; HRMS (ESI) m/z
calcd for C23H15FO (M+H)+ 327.1185, found 327.1182.
(E)‐1‐(4‐Chlorophenyl)‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐en‐1‐
one (3c). Pale yellow solid; (1.53 gm, 90% yield); mp 109.1‐112.1°C.
1H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 15.2 Hz, 1H), 7.93 (d, J =
8.4 Hz, 2H), 7.77‐7.74 (m, 1H), 7.62‐7.56 (m, 2H), 7.52‐7.50 (m, 2H),
7.44‐7.36 ppm (m, 7H); 13C NMR (100 MHz, CDCl3): δ = 190.1, 143.5,
139.0, 136.4, 135.8, 132.9, 131.5, 130.0, 129.9, 128.8, 128.7, 128.5,
128.4, 126.7, 124.4, 123.7, 122.6, 95.8, 87.0 ppm; HRMS (ESI) m/z
calcd for C23H15ClO (M+H)+ 343.0889, found 343.0888
General procedure for the synthesis of α,β‐unsaturated
ketones/Chalcones (3a‐o):
To the 25 mL RB flask added 2‐bromo‐benzaldehyde
mmol) followed by 10 ml methanol and acetophenone
1
2
(5
(5
mmol). The 10% NaOH (1.5 mL) was added dropwise for 15
min. at 0oC. The reaction mixture was allowed to stir at room
temperature for 3‐24 h. After completion of reaction as
indicated by TLC, the reaction mixture was poured onto 50 gm
of crushed ice to precipitate the reaction mixture. The
precipitate formed was washed with dist. water (2 X 10 mL)
and a cold ethanol solution (5 mL) and dried to yield the
desired product. Alternatively, methanol was evaporated
under reduced pressure and extracted with ethyl acetate (2 X
50 mL). The combined organic layer was washed with distilled
water (2 x 10 mL) and finally with brine solution (10 mL). The
separated organic layer was dried over anhydrous Na2SO4 and
concentrated under vacuum to yield the crude product. The
crude product was purified by chromatography on silica gel
using ethyl acetate/hexane as the eluent to yield the 3a‐o as
the desired product.
(E)‐1‐(2,4‐Dichlorophenyl)‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐
en‐1‐one (3d). Yellow solid; (1.64 gm, 87% yield); mp 146‐148°C; 1H
NMR (400 MHz, CDCl3) δ = 7.92 (d, J = 16.0 Hz, 1H), 7.68‐7.66 (m,
1H), 7.51‐7.49 (m, 1H), 7.38‐7.37 (m, 1H), 7.36‐7.28 (m, 6H), 7.24‐
7.22 (m, 3H), 7.07‐7.03 ppm (m, 1H); 13C NMR (100 MHz, CDCl3) δ =
193.7, 145.7, 137.2, 136.5, 135.2, 132.7, 132.3, 131.4, 130.6, 130.2,
130.0, 128.8, 128.6, 128.4, 127.4, 127.1, 126.1, 124.7, 122.3, 95.9,
86.4 ppm; HRMS (ESI) m/z calcd for C23H14Cl2O (M+H)+ 377.0500,
found 377.0505.
(E)‐3‐(2‐(Phenylethynyl)phenyl)‐1‐(p‐tolyl)prop‐2‐en‐1‐one (3e).
1
Yellow solid; (1.49 gm, 93% yield); mp 95.6‐98.5 °C; H NMR (400
MHz, CDCl3) δ = 8.34 (d, J = 16.0 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H),
7.77‐7.75 (m, 1H), 7.65‐7.58 (m, 2H), 7.54‐7.52 (m, 2H), 7.37‐7.33
(m, 5H), 7.25 (d, J = 8.4 Hz, 2H ), 2.40 ppm (s, 3H); 13C NMR (100
MHz, CDCl3) δ = 190.7, 143.4, 142.5, 136.2, 135.5, 132.9, 131.6,
129.7, 129.2, 128.7, 128.6, 128.5, 128.3, 126.6, 124.2, 124.1, 122.7,
95.7, 87.1, 21.6 ppm; HRMS (ESI) m/z calcd for C24H18O (M+H)+,
323.1436, found 323.1455.
(E)‐1‐(4‐Methoxyphenyl)‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐en‐
1‐one (3f). Yellow solid; (1.82 gm, 94% yield); 79.6‐83.3 mp 79.6‐
84.3 °C; 1H NMR (400 MHz, CDCl3) δ = 8.32 (d, J = 16.0 Hz, 1H), 8.03
General procedure for the synthesis of indenes and
cyclopenta[b]quinolines (5a‐7h):
To the 10 mL RB flask was added α,β‐unsaturated ketone
(0.5 mmol), Cs2CO3 (15–30 mol%), and cyanoacetates/malonic
esters (0.6 mmol) and allowed to stir at room temperature or
3
4
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(d, J = 8.4 Hz, 2H), 7.78‐7.75 (m, 1H), 7.63 (d, J = 16.0 Hz, 1H), 7.62‐ 165.5 (d, J = 253.6 Hz), 148.4, 143.3, 141.0, 134.1(d, J = 2.8 Hz),
7.59 (m, 1H), 7.56‐7.55 (m, 2H), 7.39‐7.36 (m, 5H), 6.94 (d, J = 9.1 133.9, 132.2, 131.3, 131.2, 131.1, 129.5, 129.4, 129.1, 128.4, 127.9
Hz, 2H), 3.86 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 189.3, (d, J = 20.9 Hz), 126.8, 124.9, 121.5, 115.8 (d, J = 21.9 Hz), 94.9, 87.2
163.2, 142.0, 136.3, 132.9, 131.6, 130.9, 130.8, 129.6, 128.6, 128.5, ppm; HRMS (ESI) m/z calcd for C26H16FNO (M+H)+ 378.1294, found
128.3, 126.7, 124.1, 123.9, 122.7, 113.7, 95.6, 87.2, 55.4 ppm; 378.1274.
HRMS (ESI) m/z calcd for C24H18O2(M+H)+ 339.1385, found
339.1364.
(E)‐3‐(2‐(Phenylethynyl)quinolin‐3‐yl)‐1‐(p‐tolyl)prop‐2‐en‐1‐one
(3m). Colourless solid; (1.75 gm, 94% yield); mp 135.2‐139.9 °C; H
NMR (400 MHz, CDCl3) δ = 8.51 (s, 1H), 8.46 (d, J = 16.0 Hz, 1H), 8.12
1
(E)‐3‐(5‐Fluoro‐2‐(phenylethynyl)phenyl)‐1‐phenylprop‐2‐en‐1‐
1
one (3g). Yellow solid; (0.98 gm, 88% yield); mp 84.1‐87.8 °C; H (d, J = 9.1 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 7.6 Hz, 1H),
NMR (400 MHz, CDCl3) δ = 8.29 (d, J = 16.0 Hz, 1H), 8.01 (d, J = 7.6 7.78‐7.74 (m, 2H), 7.69‐7.67 (m, 2H), 7.58 (t, J = 8.4 Hz, 1H), 7.42‐
Hz, 2H), 7.62‐7.60 (m, 1H), 7.59‐7.57 (m, 2H), 7.54‐7.44 (m, 5H), 7.36 (m, 3H), 7.29 (d, J = 8.0 Hz, 2H), 2.43 ppm (s, 3H); 13C NMR (100
7.37‐7.34 (m, 3H), 7.10 ppm (td, J = 8.4, 3.0, Hz, 1H); 13C NMR (100 MHz, CDCl3) δ = 189.9, 148.3, 143.7, 143.4, 140.3, 135.2, 133.7,
MHz, CDCl3) δ = 190.6, 162.2 (d, J = 248.8 Hz), 141.6, 138.3,138.2, 132.3, 131.0, 129.6, 129.4, 129.3, 129.0, 128.7, 128.4, 128.0, 127.7,
137.8, 134.7 (d, J = 7.6 Hz), 132.8, 131.5, 128.6, 128.5 (d, J = 6.6 Hz), 126.8, 125.4, 121.6, 94.9, 87.2, 21.6 ppm; HRMS (ESI) m/z calcd for
128.3, 124.9, 122.5, 120.5, 117.3 (d, J = 22.8 Hz), 113.1 (d, J = 22.8 C27H19NO (M+H)+ 374.1544, found 374.1543.
Hz), 95.4, 86.1 ppm; HRMS (ESI) m/z calcd for C23H15FO (M+H)+
327.1185, found 327.1184.
(E)‐3‐(4,5‐Dimethoxy‐2‐(phenylethynyl)phenyl)‐1‐phenylprop‐2‐
(E)‐1‐Phenyl‐3‐(2‐(p‐tolylethynyl)quinolin‐3‐yl)prop‐2‐en‐1‐one
(3n). Colourless solid; (1.69 53 gm, 90% yield); mp 185.5‐188.6 °C;
1H NMR (400 MHz, CDCl3) δ = 8.42 (s, 1H), 8.37 (d, J = 16.0 Hz,1H),
en‐1‐one (3h). Yellow solid; (1.65 gm, 90% yield); mp 147.1‐140.3 8.03 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 6.8 Hz, 2H), 7.78 (d, J = 7.6 Hz,
°C; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 16.0 Hz, 1H), 7.99 (d, J = 1H), 7.70‐7.67 (m, 2H), 7.55‐7.48 (m, 4H), 7.42 (t, J = 7.6 Hz, 2H),
7.6 Hz, 2H), 7.58‐7.55 (m, 1H), 7.49‐7.45 (m, 5H), 7.35‐7.33 (m, 3H), 7.11 (d, J = 7.6 Hz, 2H); 2.32 ppm (s, 3H); 13C NMR (100 MHz, CDCl3)
7.20 (s, 1H), 7.05 (s, 1H), 3.98 (s, 3H), 3.95 ppm (s, 3H); 13C NMR δ = 190.5, 148.4, 143.5, 140.9, 139.9, 137.8, 133.8, 132.8, 132.2,
(100 MHz, CDCl3) δ = 191.6, 150.7, 149.5, 143.3, 138.4, 132.3, 131.4, 131.1, 129.5, 129.2, 129.0, 128.7, 128.6, 128.0, 127.6, 126.7, 125.4,
129.5, 128.5, 128.4, 128.3, 122.8, 122.2, 118.1, 114.4, 108.4, 94.7, 118.5, 95.4, 86.8, 21.6 ppm; HRMS (ESI) m/z calcd for C27H19NO
87.1, 56.0, 55.9 ppm; HRMS (ESI) m/z calcd for C25H20O3 (M+H)+ (M+H)+, 374.1544, found 374.1542.
369.1490 found 369.1480.
(E)‐1‐(Furan‐2‐yl)‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐en‐1‐one
(E)‐3‐(2‐(Phenylethynyl)quinolin‐3‐yl)‐1‐(thiophen‐2‐yl)prop‐2‐
en‐1‐one (3o). Pale yellow solid; (1.55 gm, 85% yield); mp 163.1‐
(3i). Pale yellow solid; (1.35 gm, 91% yield); mp 84.5‐87.1 °C; 1H 165.5 °C; 1H NMR (400 MHz, CDCl3) δ = 8.54‐8.49 (m, 2H), 8.11 (d, J
NMR (400 MHz, CDCl3) δ = 8.38 (d, J = 16.0 Hz, 1H), 7.70‐7.67 (m, = 8.4 Hz, 1H), 7.91 (d, J = 3.8 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.77‐
1H), 7.55‐7.51 (m, 5H), 7.32‐7.24 (m, 6H), 6.49‐6.48 ppm (m, 1H); 7.65 (m, 5H), 7.57 (t, J = 6.8 Hz, 1H), 7.42‐7.39 (m, 3H), 7.17 ppm (t,
13C NMR (100 MHz, CDCl3) δ = 178.1, 153.6, 146.4, 141.9, 135.9, J = 3.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ = 181.6, 148.4, 145.1,
132.9, 131.6, 129.9, 128.6, 128.4, 128.3, 126.8, 124.4, 122.8, 122.7, 143.4, 139.9, 134.3, 133.8, 132.3, 132.1, 131.1, 129.5, 129.4, 129.1,
117.5, 112.5, 95.8, 87.1 ppm; HRMS (ESI) m/z calcd for C21H14O2 128.4, 128.3, 128.0, 127.8, 126.8, 124.8, 121.6, 95.0, 87.2 ppm;
(M+H)+ 299.1072 found 299.1065.
HRMS(ESI) m/z calcd for C24H16NOS (M+H)+, calculated 366.0925,
(E)‐3‐(2‐(Phenylethynyl)phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐on‐ found 366.0952.
e (3j). Pale yellow solid; (1.50 gm, 96% yield); mp 134.5‐137.9 °C; 1H
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,3‐
NMR (400 MHz, CDCl3) δ = 8.43 (d, J = 16.0 Hz, 1H), 7.85 (d, J = 3.8 dihydro‐1H‐indene‐2‐carboxylate (5a). Colorless solid; (179 mg,
Hz, 1H), 7.77‐7.75 (m, 1H),7.66 (d, J = 4.5 Hz,1H), 7.61‐7.54 (m, 4H), 85% yield); mp 153.1‐156.2 °C; 1H NMR (400 MHz, CDCl3) δ = 8.03
7.39 ‐7.35 (m, 5H), 7.14 ppm (t, J = 3.8 Hz, 1H); 13C NMR (100 MHz, (d, J = 7.8 Hz, 2H), 7.62‐7.58 (m, 2H), 7.51‐7.47 (m, 4H), 7.40‐7.20
CDCl3) δ = 182.2, 145.4, 142.0, 135.8, 133.9, 132.9, 131.9, 131.6, (m, 6H), 7.21‐7.19 (m, 1H), 4.61 (t, J = 6.0 Hz, 1H), 3.86‐3.70 (m, 2H),
129.9, 128.6, 128.5, 128.4, 128.2, 126.6, 124.4, 123.3, 122.7, 95.8, 3.36 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 197.1, 167.6,
87.1 ppm; HRMS (ESI) m/z calcd for C21H14OS (M+H)+ 315.0843 142.1, 138.8, 138.4, 136.1, 134.9, 133.6, 129.7, 128.8, 128.7, 128.6,
found 315.0860.
128.3, 128.1, 128.0, 125.6, 123.7, 121.0, 117.4, 57.0, 53.2, 48.8,
(E)‐1‐(4‐Bromophenyl)‐3‐(2‐(phenylethynyl)phenyl)prop‐2‐en‐1‐
one (3k). Pale yellow solid; (1.80 gm, 93% yield); 108.1‐111.2 °C; 1H found 425.1869.
41.1 ppm; HRMS (ESI) m/z calcd for C27H21NO3 (M+NH4)+ 425.1865,
NMR (400 MHz, CDCl3) δ = 8.32 (d, J = 16.0 Hz, 1H), 7.85 (d, J = 9.9
Hz, 2H), 7.76‐74 (m, 1H), 7.61‐7.49 (m, 6H), 7.39‐7.36 ppm (m, 5H);
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(4‐fluorophenyl)‐2‐oxoe‐
thyl)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5b). Colorless solid;
13C NMR (100 MHz, CDCl3) δ = 190.3, 143.6, 136.8, 135.8, 132.9, (187 mg, 85% yield); mp 152.5‐155.5 °C; 1H NMR (400 MHz, CDCl3) δ
131.8, 131.5, 130.1, 128.7, 128.5, 128.4, 127.6, 126.7, 124.4, 123.6, = 8.08‐8.04 (m, 2H), 7.62‐7.60 (m, 1H), 7.48‐7.46 (m, 2H), 7.40‐7.30
122.6, 95.9, 87.0 ppm; HRMS (ESI) m/z calcd for C23H15BrO (M+H)+ (m, 6H), 7.20‐7.14 (m, 3H), 4.62‐4.58 (m, 1H), 3.83‐3.66 (m, 2H),
387.0385 found 387.0380.
3.36 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 195.5, 167.6, 166.0
(E)‐1‐(4‐Fluorophenyl)‐3‐(2‐(phenylethynyl)quinolin‐3‐yl)prop‐2‐
(d, J = 254.5 Hz), 142.0, 138.8, 138.3, 134.9, 132.6 (d, J = 2.8 Hz),
en‐1‐one (3l). Pale yellow solid; (2.14 gm, 91% yield); mp 160.1‐ 130.8 (d, J = 9.5 Hz), 129.7, 128.8, 128.7, 128.2, 128.0, 125.7, 123.6,
163.8 °C; 1H NMR (400 MHz, CDCl3) δ = 8.51 (s, 1H), 8.46 (d, J = 15.6 121.1, 117.4, 115.8 (d, J = 21.9 Hz), 56.9, 53.2, 48.8, 41.0 ppm;
Hz, 1H), 8.14‐8.08 (m, 3H), 7.87 (d, J = 8.4 Hz, 1H), 7.80‐7.74 (m, HRMS (ESI) m/z calcd for C27H20FNO3 (M+NH4)+ 443.1771, found
2H), 7.69‐7.67 (m, 2H), 7.59 (t, J = 8.4 Hz, 1H), 7.44‐7.40 (m, 3H), 443.1768.
7.16 ppm (t, J = 11.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ = 188.7,
6 | J. Name., 2012, 00, 1‐3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C7OB02498C
Journal Name
ARTICLE
(Z)‐Methyl‐1‐benzylidene‐3‐(2‐(4‐chlorophenyl)‐2‐oxoethyl)‐2‐cy
1H), 6.67 (s, 1H), 4.53 (t, J = 6.1 Hz, 1H), 3.96 (s, 3H), 3.87 (s, 3H),
ano‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5c). Colorless solid; (200 3.82 (dd, J1 = 18.3, J2 = 7.6 Hz, 1H), 3.66 (dd, J1 = 19.1, J 2 = 6.2 Hz,
1
mg, 87% yield); mp 128.7‐131.5 °C; H NMR (400 MHz, CDCl3) δ = 1H), 3.38 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 197.3, 167.7,
8.06‐8.02 (m, 2H), 7.59 (d, J = 7.2 Hz, 1H), 7.46‐744 (m, 2H), 738‐ 151.2, 150.1, 138.4, 136.2, 135.1, 135.0, 133.6, 131.2, 128.7, 128.7,
7.29 (m, 6H), 7.18‐7.11 (m, 3H), 4.58 (t, J = 6.8 Hz, 1H), 3.81‐3.64 128.2, 128.1, 127.6, 123.0, 117.5, 105.9, 103.0, 57.0, 56.1, 53.2,
(m, 2H), 3.31 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 196.0, 48.6, 41.4 ppm; HRMS (ESI) m/z calcd for C29H25NO5 (M+NH4)+
167.6, 141.9, 140.1, 138.8, 138.3, 134.9, 134.5, 129.7, 129.6, 129.0, 485.2076, found 485.2064.
128.8, 128.7, 128.3, 128.0, 125.7, 123.6, 121.1, 117.4, 56.9, 53.2,
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(furan‐2‐yl)‐2‐oxoethyl)‐2,‐
48.8, 41.1 ppm; HRMS (ESI) m/z calcd for C27H20ClNO3 (M+NH4)+ 3 ‐dihydro‐1H‐indene‐2‐carboxylate (5i). Colorless solid; (203 mg,
1
459.1475, found 459.1477.
92% yield); mp 139.4‐142.4 °C; H NMR (400 MHz, CDCl3) δ = 7.63
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(2,4‐dIchlorophenyl‐2‐
(s, 1H), 7.60 (d, J = 6.8 Hz, 1H), 7.49‐7.47 (m, 2H), 7.39‐7.27 (m, 7H),
oxo‐ethyl)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5d). Colorless 7.20‐7.18 (m, 1H), 6.58‐6.56 (m, 1H), 4.58 (t, J = 6.8 Hz, 1H), 3.85‐
1
white solid; (171 mg, 72% yield); mp 132.3‐135.6°C; H NMR (400 3.78 (m, 1H), 3.75‐3.66 (m, 2H), 3.62‐3.56 (m, 1H), 0.99 ppm (t, J =
MHz, CDCl3) δ = 7.60 (t, J = 8.4 Hz, 2H), 7.46‐7.44 (m, 3H), 7.39‐7.29 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 185.7 166.9, 152.0,
(m, 7H), 7.24‐7.20 (m, 1H), 4.57 (t, J = 6.0 Hz, 1H), 3.74‐3.72 (m, 2H), 146.9, 141.9, 139.0, 137.8, 135.1, 129.7, 128.8, 128.7, 128.3, 128.0,
3.36 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 198.7, 167.7, 141.5, 125.5, 123.7, 121.0, 118.0, 117.3, 112.4, 62.9, 57.2, 48.4, 40.5, 13.3
138.8, 138.2, 138.0, 136.3, 134.7, 132.1, 130.7, 130.5, 129.8, 128.8, ppm; HRMS (ESI) m/z calcd for C26H21NO4 (M+NH4)+ 429.1814,
128.3, 128.0, 127.5, 125.8, 123.5, 121.1, 117.3, 56.7, 53.3, 48.9, found 429.1805.
45.4 ppm; HRMS (ESI) m/z calcd for C27H19C2lNO3 (M+NH4)+
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐(thiophen‐2‐yl)ethyl‐
493.1085, found 493.1097.
)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5j). Colorless solid; (205
1
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐ 2,3‐ mg, 96% yield); mp 155.6‐157.5 °C; H NMR (400 MHz, CDCl3) δ =
dihydro‐1H‐indene‐2‐carboxylate (5e). Colorless solid; (199 mg, 7.86 (d, J = 3.4 Hz, 1H), 7.69 (d, J = 4.5 Hz, 1H), 7.60 (d, J = 6.8 Hz,
94% yield); mp 138.7‐142.8 °C; H NMR (400 MHz, CDCl3) δ = 7.93 1H), 7.49‐7.47 (m, 2H), 7.38‐7.25 (m, 6H), 7.19‐7.15 (m, 2H), 4.61 (t,
1
(d, J = 8.4 Hz, 2H), 7.61‐7.59 (m, 1H), 7.49‐7.47 (m, 2H), 7.39‐7.29 J = 6.9 Hz, 1H), 3.84‐3.62 (m, 4H), 0.98 ppm (t, J = 7.6 Hz, 3H); 13C
(m, 8H), 7.20‐7.18 (m, 1H), 4.61 (t, J = 6.0Hz, 1H), 3.82‐3.72 (m, 2H), NMR (100 MHz, CDCl3) δ = 189.6, 166.9, 143.3, 141.9, 139.0, 137.8,
3.35 (s, 3H), 2.41 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 196.6, 135.1, 134.4, 132.7, 129.7, 128.7, 128.6, 128.3, 128.0, 125.5, 123.7,
167.6, 144.5, 142.2, 138.8, 138.4, 134.9, 133.7, 129.7, 129.3, 128.7, 121.0, 117.4, 62.9, 57.2, 48.8, 41.3, 13.3 ppm; HRMS (ESI) m/z calcd
128.6, 128.2, 127.9, 125.5, 123.7, 121.0, 117.4, 57.0, 53.1, 48.8, for C26H21NO3 (M+NH4)+ 445.1585, found 445.1582.
40.9, 21.6 ppm; HRMS (ESI) m/z calcd for C28H23NO3 (M+Na)+
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,3‐dih‐
444.1575, found 444.1592.
ydro‐1H‐indene‐2‐carboxylate (5k). Colorless solid; (168 mg, 80%
1
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(4‐methoxyphenyl)‐2‐ox ‐ yield); mp 146‐148°C; H NMR (400 MHz, CDCl3) δ = 8.05‐8.03 (m,
oethyl)‐2,3‐dihy dro‐1H‐indene‐2‐carboxylate (5f). Pale yellow 2H), 7.61‐7.60 (m, 2H), 7.51‐7.47 (m, 4H), 7.39‐7.27 (m, 6H), 7.20‐
solid; (201 mg, 92% yield); mp 112.2‐115.7 °C; H NMR (400 MHz, 7.18 (m, 1H), 4.63 (t, J = 6.8 Hz, 1H), 3.88‐3.81 (m, 2H), 3.75‐3.69
1
CDCl3) δ 8.00 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 6.8 Hz, 1H), 7.47‐7.45 (m, 2H), 1.00 ppm (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ =
(m, 2H), 7.39‐7.28 (m, 6H), 7.20‐7.18 (m, 1H), 6.94 (d, J = 8.2 Hz, 197.0, 167.1, 142.2, 139.0, 138.0, 136.2, 135.1, 133.5, 129.6, 128.8,
2H), 4.60 (t, J = 6.1 Hz, 1H), 3.86 (s, 3H), 3.79‐3.64 (m, 2H), 3.34 ppm 128.7, 128.5, 128.3, 128.1, 128.0, 125.5, 123.7, 121.0, 62.8, 57.2,
(s, 3H); 13C NMR (100 MHz, CDCl3) δ = 195.4, 167.6, 163.8, 142.3, 48.8, 41.0, 13.4 ppm; HRMS (ESI) m/z calcd for C28H23NO3 (M+NH4)+
138.8, 138.4, 134.9, 130.5, 129.7, 129.2, 128.7, 128.5, 128.2, 127.9, 439.2021, found 439.2021.
125.5, 123.7, 121.0, 117.5, 113.8, 57.0, 55.4, 53.1, 48.9, 40.6 ppm;
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(4‐fluorophenyl)‐2‐oxoethy‐
HRMS (ESI) m/z calcd for C28H23NO4 (M+NH4)+ 460.1524, found l)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5l). Colorless solid; (165
1
460.1526.
mg, 75% yield); mp 117.8‐120.8 °C; H NMR (400 MHz, CDCl3) δ =
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐5‐fluoro‐3‐(2‐oxo‐2‐phenylet ‐ 8.08‐8.05 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.49‐7.47 (m, 2H), 7.39‐
hyl)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5g). Colorless solid; (185 7.29 (m, 6H), 7.19‐7.14 (m, 3H), 4.62 (t, J = 6.0 Hz, 1H), 3.88‐3.77
1
mg, 87% yield); mp 164.5‐166.8 °C; H NMR (400 MHz, CDCl3) δ = (m, 2H), 3.74‐3.64 (m, 2H), 1.00 ppm (t, J = 7.2 Hz, 3H); 13C NMR
8.02 (d, J = 8.4 Hz, 2H), 7.62‐7.54 (m, 2H), 7.50‐7.44 (m, 4H), 7.38 (t, (100 MHz, CDCl3) = δ 195.4, 167.2, 165.9 (d, J = 238.3 Hz), 142.0,
J = 7.6 Hz, 2H), 7.32‐7.28 (m, 1H), 7.21 (s, 1H), 7.06 (t, J = 8.0 Hz, 139.0, 137.9, 135.0, 132.6 (d, J = 2.8 Hz), 130.7 (d, J = 8.5 Hz),
1H), 6.91‐6.89 (m, 1H), 4.57 (t, J = 6.0 Hz, 1H), 3.85‐3.64 (m, 2H), 129.7, 128.8, 128.6, 128.3, 128.0, 125.6, 123.6, 121.0, 117.4, 115.8,
3.35 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ = 196.7, 167.4, 163.8 (d, J = 21.9 Hz), 62.8, 57.1, 48.8, 40.9, 13.3 ppm; HRMS (ESI) m/z
(d, J = 254.6 Hz), 144.4, 144.3, 137.1, 135.9, 134.7, 133.7, 128.7, calcd for C28H22FNO3 (M+NH4)+ 457.1927, found 457.1918.
128.3, 128.2 , 128.1, 125.3, 122.6, 122.5, 117.2, 116.2 (d, J = 22.8
(Z)‐Ethyl‐1‐benzylidene‐3‐(2‐(4‐chlorophenyl)‐2‐oxoethyl)‐2‐cya‐
Hz), 111.0 (d, J = 22.8 Hz), 57.2, 53.3, 48.5, 40.9 ppm; HRMS (ESI) no‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5m). Colorless solid; (179
1
m/z calcd for C27H20FNO3 (M+NH4)+ 443.1771, found 443.1750
(Z)‐Methyl‐1‐benzylidene‐2‐cyano‐5,6‐dimethoxy‐3‐(2‐oxo‐2‐phe‐
mg, 80% yield); mp 137.1‐140.4 °C; H NMR (400 MHz, CDCl3) δ =
7.91(d, J = 9.1 Hz, 2H), 7.55‐7.53 (m, 1H), 7.42‐7.39 (m, 4H), 7.32‐
nylethyl)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5h). Colorless 7.18 (m, 6H), 7.12‐7.10 (m, 1H), 4.54 (t, J = 6.8 Hz, 1H), 3.80‐3.70
solid; (200 mg, 86% yield); mp 167‐169 °C; 1H NMR (400 MHz, (m, 2H), 3.67‐3.56 (m, 2H), 0.94 ppm (t, J = 6.8 Hz, 3H); 13C NMR
CDCl3): δ = 8.03 (d, J = 7.6 Hz, 2H), 7.60‐7.58 (m, 1H), 7.51‐7.45 (m, (100 MHz, CDCl3) δ = 195.8, 167.1, 142.0, 140.1, 139.0, 137.9, 135.0,
4H), 7.37 (t, J = 7.6 Hz, 2H), 7.30‐7.28 (m, 1H), 7.09 (s, 1H), 7.04 (s, 134.5, 129.7, 129.6, 129.0, 128.8, 128.6, 128.3, 128.0, 125.6, 123.6,
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121.1, 117.4, 62.9,57.1, 48.8, 41.0, 13.4 ppm; HRMS (ESI) m/z calcd 8.0 Hz, 2H), 7.62‐7.58 (m, 2H), 7.51‐7.47 (m, 4H), 7.39‐7.29 (m, 6H),
for C28H22ClNO3 (M+NH4)+ 473.1632, found 473.1616.
7.20‐7.18 (m, 1H), 4.63 (t, J = 6.0 Hz, 1H), 3.87‐3.79 (m, 2H), 3.73‐
(Z)‐Ethyl‐1‐benzylidene‐3‐(2‐(4‐bromophenyl)‐2‐oxoethyl)‐2‐cya‐
3.67 (m, 1H), 3.64‐3.58 (m, 1H), 1.41‐1.32 (m, 2H), 1.31‐1.18 (m,
no‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5n). Colorless solid; (205 2H), 0.82 ppm (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ =
1
mg, 82% yield); mp 138.5‐141.7 °C; H NMR (400 MHz, CDCl3) δ = 196.9, 167.1, 142.3, 139.0, 138.0, 136.2, 135.0, 133.5, 129.6, 128.8,
7.90 (d, J = 8.4 Hz, 2H), 7.65‐7.60 (m, 3H), 7.48 (d, J = 6.8 Hz, 2H), 128.7, 128.6, 128.3, 128.2, 128.0, 125.5, 123.7, 121.0, 117.4, 66.6,
7.39‐7.29 (m, 6H), 7.19‐7.17 (m, 1H), 4.61 (t, J = 5.3 Hz, 1H), 3.88‐ 57.2, 48.8, 41.1, 29.8, 18.8, 13.5 ppm; HRMS (ESI) m/z calcd for
3.76 (m, 2H), 3.72‐3.62 (m, 2H), 1.00 ppm (t, J = 7.6 Hz, 3H); 13C C30H27NO3 (M+NH4)+ 467.2334, found 467.2332.
NMR (100 MHz, CDCl3) δ = 196.0, 167.1, 142.0, 139.0, 137.9, 135.0,
(Z)‐Isopropyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,3‐
134.9, 132.0, 129.6, 128.9, 128.8, 128.6, 128.3, 128.0, 125.6, 123.6, dihydro‐1H‐indene‐2‐carboxylate (5t). Colorless solid; (203 mg,
121.1, 117.4, 62.9, 57.1, 48.7, 41.0, 13.4 ppm; HRMS (ESI) m/z calcd 93% yield); mp 146‐148°C; 1H NMR (400 MHz, CDCl3) δ = 8.06 (d, J =
for C28H22BrNO3 (M+Na)+ 522.0680, found 522.0689.
7.6 Hz, 2H), 7.62‐7.60 (m, 2H), 7.53‐7.48 (m, 4H), 7.40‐7.28 (m, 6H),
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐3‐(2‐(2,4‐dichlorophenyl)‐2‐oxo‐ 7.18‐7.16 (m, 1H), 4.73‐4.63 m, 2H), 3.88‐3.66(m, 2H), 1.04‐1.02
ethyl)‐2,3‐di hydro‐1H‐indene‐2‐carboxylate (5o). Colorless solid; (m, 3H), 0.88‐0.87 ppm (m, 3H); 13C NMR (100 MHz, CDCl3) δ =
(165 mg, 70% yield); mp 106.7‐109.8 °C; 1H NMR (400 MHz, CDCl3) δ 196.8, 166.5, 142.3, 139.2, 137.2, 136.2, 135.1, 133.6, 129.6, 128.9,
= 7.56‐7.52 (m, 2H), 7.42‐7.40 (m, 3H), 7.33‐7.28 (m, 5H), 7.25‐7.14 128.7, 128.5, 128.4, 128.2, 128.1, 125.4, 123.8, 121.0, 117.5, 57.5,
(m, 3H), 4.52 (t, J = 6.8 Hz, 1H), 3.83‐3.79 (m, 1H), 3.68‐3.62 (m, 3H), 48.9, 41.2, 21.2, 20.8 ppm; HRMS (ESI) m/z calcd for C29H25NO3
0.97 ppm (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) = δ 198.6, (M+NH4)+ 453.2178, found 453.2174.
167.2, 141.7, 139.0, 137.9, 136.4, 134.9, 132.1, 130.7, 130.5, 129.7,
(Z)‐tert‐Butyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,‐
128.9, 128.7, 128.3, 128.1, 127.5, 125.8, 123.5, 121.1, 117.3, 63.0, 3‐di hydro‐1H‐indene‐2‐carboxylate (5u): Colorless solid; (211 mg,
56.9, 48.9, 45.4, 13.4 ppm; HRMS (ESI) m/z calcd for C28H21Cl2NO3 94% yield); mp 146‐148°C; 1H NMR (400 MHz, CDCl3) δ = 8.08 (d, J =
(M+NH4)+ 507.1242, found 507.1251.
8.0 Hz, 2H), 7.61‐7.55 (m, 4H), 7.50 (t, J = 7.6 Hz, 2H), 7.39 (t, J = 7.6
(Z)‐Ethyl1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐2,3‐dih‐ Hz, 2H), 7.36‐7.27 (m, 4H), 7.16‐7.14 (m, 1H), 4.65 (t, J = 6.8 Hz, 1H),
ydro‐1H‐inden e‐2‐carboxylate (5p). Colorless solid; (200 mg, 92% 3.85‐3.65 (m, 2H), 1.15 ppm (s, 9H); 13C NMR (100 MHz, CDCl3) δ =
yield); mp 146‐148°C; 1H NMR (400 MHz, CDCl3) δ = 7.94 (d, J = 8.4 196.9, 165.8, 142.6, 139.4, 137.1, 136.3, 135.4, 133.6, 129.5, 129.0,
Hz, 2H), 7.60 (d, J = 6.8 Hz, 1H), 7.50‐7.48 (m, 2H), 7.39‐7.33 (m, 128.7, 128.6, 128.4, 128.2, 128.0, 125.3, 123.9, 120.9, 117.7, 84.3,
3H), 7.31‐7.27 (m, 5H), 7.19‐7.17 (m, 1H), 4.62 (t, J = 6.4 Hz, 1H), 57.9, 48.9, 41.6, 27.1 ppm; HRMS (ESI) m/z calcd for C30H27NO3
3.87‐3.77 (m, 2H), 3.74‐3.66 ( m, 2H), 2.42 (s, 3H), 0.99 ppm (t, J = (M+Na)+ 472.1888, found 472.1872.
6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 196.5, 167.1, 144.5,
(E)‐Methyl‐3‐benzylidene‐2‐cyano‐1‐(2‐(4‐fluorophenyl)‐2‐oxoet‐
142.2, 139.0, 138.0, 135.1, 133.7, 129.6, 129.3, 128.8, 128.5, 128.3, hyl)‐2,3‐dihydro‐1H‐cyclo‐penta[b]quinoline‐2‐carboxylate (6a).
1
128.3, 128.0, 125.5, 123.7, 121.0, 117.5, 62.8, 57.2, 48.8, 40.9, 21.6, Colorless solid; (214 mg, 90% yield); mp 162‐165 °C; H NMR (400
13.4 ppm; HRMS (ESI) m/z calcd for C29H25NO3 (M+Na)+ 458.1732, MHz, CDCl3) δ = 8.20 (s, 1H), 8.14‐8.09 (m, 3H), 7.95 (s, 1H), 7.78‐
found 458.1742.
7.73 (m, 2H), 7.60‐7.58 (m, 2H), 7.55‐7.51 (m, 1H), 7.45‐7.41 (m,
(Z)‐Ethyl‐1‐benzylidene‐2‐cyano‐5‐fluoro‐3‐(2‐oxo‐2‐phenylethyl
2H), 7.38‐7.37 (m, 1H), 7.21‐7.16 (m, 2H), 4.70 (t, J = 6.8 Hz, 1H),
)‐2,3‐dihydro‐1H‐indene‐2‐carboxylate (5q). Colourless solid; (167 3.94‐3.79 (m, 2H), 3.44 ppm (s, 3H); 13C NMR (100 MHz, CDCl3) δ =
1
mg, 75%), mp 121‐124 °C; H NMR (400 MHz, CDCl3) δ = 8.08‐8.05 195.1, 167.4, 164.8, 157.4, 149.0, 135.5, 134.4, 133.6, 132.4, 131.5,
(m, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.49‐7.47 (m, 2H), 7.39‐7.29 (m, 131.2, 130.9 (d, J = 9.5 Hz), 130.0, 129.3, 129.2, 128.8, 128.4, 128.2,
6H), 7.19‐7.13 (m, 3H), 4.62 (t, J = 6.8 Hz, 1H), 3.88‐3.82 (m, 2H), 127.8, 126.8, 118.8, 116.0 (d, J = 21.9Hz), 55.3, 53.5, 46.1, 41.4
3.81‐3.64 (m, 2H), 1.00 ppm (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, ppm; HRMS (ESI) m/z calcd for C30H21FN2O3 (M+H)+ 477.1614,
CDCl3) δ = 195.4, 166.8, 163.8 (d, J = 248.8 Hz), 144.5, 144.4, 136.8, found 477.1629.
136.0, 135.0, 134.9, 133.7, 128.7, 128.2 (d, J = 19.0 Hz), 128.0,
125.2, 122.5, 122.4, 117.2, 116.1 (d, J = 22.8 Hz), 111.1 (d, J = 23.8
(E)‐Butyl‐3‐benzylidene‐2‐cyano‐1‐(2‐(4‐fluorophenyl)‐2‐oxoeth‐
yl)‐2,3‐dihydro‐1H‐cyclo‐penta[b]quinoline‐2‐carboxylate (6b):
Hz), 63.0, 57.4, 48.5, 40.9, 13.3 ppm; HRMS (ESI) m/z calcd for Colorless solid; (243 mg, 94% yield); mp 145.1‐148.5 °C; 1H NMR
C28H22FNO3 (M+NH4)+ 457.1927, found 457.1918.
(400 MHz, CDCl3) δ = 8.20 (s, 1H), 8.14‐8.10 (m, 3H), 7.95 (s, 1H),
(Z)‐Propyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,3‐di‐ 7.78‐7.71 (m, 2H), 7.62‐7.60 (m, 2H), 7.54‐7.50 (m, 1H), 7.43 (t, J =
hydro‐1H‐inde ne‐2‐carboxylate (5r). Colorless solid; (200 mg, 91% 8.0 Hz, 2H), 7.36‐7.34 (m, 1H), 7.20 (t, J = 9.1 Hz, 2H), 4.70 (t, J = 6.8
yield); mp 163.5‐166.1 °C; 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J = Hz, 1H), 3.96‐3.85 (m, 2H), 3.81‐3.73 (m, 2H), 1.41‐1.33 (m, 2H),
8.0 Hz, 2H), 7.62‐7.58 (m, 2H), 7.51‐7.47 (m, 4H), 7.41‐7.27 (m, 6H), 1.28‐1.16 (m, 2H), 0.81 ppm (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz,
7.20‐7.19 (m, 1H), 4.64 (t, J = 6.0 Hz, 1H), 3.88‐3.68 (m, 3H), 3.60‐ CDCl3) δ = 195.0, 166.9, 166.1 (d, J = 255.5 Hz), 157.6, 149.0, 135.1,
3.54 (m, 1H), 1.58‐1.39 (m, 2H), 0.79 ppm (t, J = 7.6 Hz, 3H); 13C 134.5, 133.8, 132.5, 132.4, 131.3, (d, J = 30.2 Hz), 131.0 (d, J = 9.5
NMR (100 MHz, CDCl3) δ = 196.9, 167.1, 142.2, 139.0, 138.0, 136.2, Hz), 130.0, 129.4, 129.2, 128.9, 128.4, 128.2, 127.8, 126.7, 116.7,
135.0, 133.5, 129.6, 128.8, 128.7, 128.6, 128.3, 128.1, 127.9, 125.5, 116.5 (d, J = 21.9 Hz), 67.0, 55.5, 46.1, 41.5, 29.8, 18.8, 13.5 ppm;
123.7, 121.0, 117.4, 68.3, 57.2, 48.8, 41.1, 21.2, 10.2 ppm; HRMS HRMS (ESI) m/z calcd for C33H27FN2O3 (M+H)+ 519.2084, found
(ESI) m/z calcd for C29H25NO3 (M+NH4)+ 453.2178, found 453.2174.
(Z)‐Butyl‐1‐benzylidene‐2‐cyano‐3‐(2‐oxo‐2‐phenylethyl)‐2,3‐dih‐
519.2075.
(E)‐Isopropyl‐3‐benzylidene‐2‐cyano‐1‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐2,‐
ydro‐1H‐inden e‐2‐carboxylate (5s). Colorless solid; (215 mg, 96% 3‐dihydro‐1H‐cyclo‐penta[b]quinoline‐2‐carboxylate (6c). Colorless
1
yield); mp 141.2‐143.5 °C; 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J = solid; (230 mg, 92% yield); mp 179.5‐183.8 °C; H NMR (400 MHz,
8 | J. Name., 2012, 00, 1‐3
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CDCl3) δ = 8.19 (s, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.6 Hz, mp 68‐71 °C; 1H NMR (400 MHz, CDCl3) δ = 7.78 (d, J = 8.4 Hz, 2H),
2H), 7.92 (s, 1H), 7.76‐7.69 (m, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.50 (t, J 7.57 (d, J = 7.5 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.31‐7.27 (m, 5H),
= 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.37‐7.31 (m, 3H), 4.80‐4.76 7.22‐7.17 (m, 4H), 4.97‐4.94 (m, 1H), 3.67 (s, 3H), 3.56 (dd, J1 = 18.3,
(m, 1H), 4.70 (t, J = 8.0 Hz, 1H), 3.96‐3.78 (m, 2H), 2.45 (s, 3H), 1.08 J2 = 9.6 Hz, 1H), 3.17 (s, 3H), 3.14‐3.09 (m, 1H), 2.36 ppm (s, 3H); 13
C
(d, J = 6.1 Hz, 3H), 0.85 ppm (d, J = 6.1 Hz, 3H); 13C NMR (100 MHz, NMR (100 MHz, CDCl3) δ = 197.3, 170.3, 168.6, 144.4, 143.8, 140.5,
CDCl3) δ = 196.2, 166.3, 157.8, 148.9, 144.8, 134.7, 134.6, 134.1, 139.1, 136.2, 134.0, 129.1, 129.0,128.3, 128.0, 127.9, 127.8, 127.3,
133.5, 131.4, 131.1, 129.8, 129.6, 129.5, 129.2, 129.0, 128.6, 128.4, 125.9, 124.0,120.7, 67.8, 53.1, 52.2, 48.0, 42.6, 21.5 ppm; HRMS
128.2, 127.8, 126.6, 116.9, 71.6, 55.8, 46.2, 41.5, 21.7, 21.2, 20.7 (ESI) m/z calcd for C29H26O5 (M+H)+ 455.1858, found 455.1873.
ppm; HRMS (ESI) m/z calcd for C33H28N2O3 (M+H)+ 501.2178, found
501.2145.
(E)‐Ethyl‐2‐cyano‐3‐(4‐methylbenzylidene)‐1‐(2‐oxo‐2‐phenyle
(Z)‐Dimethyl1‐benzylidene‐3‐(2‐oxo‐2‐(thiophen‐2‐yl)ethyl)‐1,3‐
dihydro‐2H‐in dene‐2,2‐dicarboxylate (7d). Pale yellow solid; (200
mg, 93% yield); mp 60‐63 °C; H NMR (400 MHz, CDCl3) δ = 7.60‐
1
thyl)‐2,3‐dihydro‐1H‐cyclo‐penta[b]quinoline‐2‐carboxylate (6d). 7.56 (m, 3H), 7.49 (d, J = 8.4 Hz, 2H), 7.32‐7.25 (m, 5H), 7.23‐7.20
1
Colorless solid; (210 mg, 86 % yield); mp 132.1‐134.1 °C; H NMR (m, 2H), 7.06‐7.03 (m, 1H), 4.94‐4.91 (m, 1H), 3.65 (s, 3H), 3.49 (dd,
(400 MHz, CDCl3) δ = 8.16 (s, 1H), 8.13‐8.09 (m, 3H), 7.93 (s, 1H), J1 = 17.5, J2 = 8.4 Hz, 1H), 3.21 (s, 3H), 3.13 ppm (dd, J1 = 17.5, J2 =
7.77‐7.69 (m, 2H), 7.65‐7.62 (m, 1H), 7.55‐7.49 (m, 5H), 7.24 (d, J = 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ = 190.6, 170.1, 168.6,
8.0 Hz, 2H), 4.71 (t, J = 6.8 Hz, 1H), 4.00‐3.90 (m, 3H), 3.85‐3.79 (m, 144.1, 143.7, 140.5, 138.9, 136.2, 133.4, 131.9, 129.0, 128.5, 128.4,
1H), 2.39 (s, 3H), 1.04 ppm (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, 128.2, 128.0, 127.4, 126.0, 124.1, 120.8, 67.8, 53.1, 52.2, 47.9, 43.1
CDCl3) δ = 196.7, 167.0, 157.9, 149.0, 139.2, 136.0, 134.1, 133.9, ppm; HRMS (ESI) m/z calcd for C26H22O5S (M+H)+ 447.1266, found
133.8, 131.7, 131.5, 131.3, 129.9, 129.5, 129.2, 128.8, 128.3, 128.2, 447.1276.
127.8, 126.6, 116.8, 63.2, 55.6, 46.1, 41.7, 21.4, 13.4 ppm; HRMS
(E)‐Dimethyl‐3‐benzylidene‐1‐(2‐(4‐fluorophenyl)‐2‐oxoethyl)‐1‐
H‐cyclopenta[b]quinoline‐2,2(3H)‐dicarboxylate (7e). Colorless
(ESI) m/z calcd for C32H26N2O3(M+H)+ 487.2021, found 487.2004.
(E)‐Ethyl‐3‐benzylidene‐2‐cyano‐1‐(2‐oxo‐2‐(thiophen‐2‐yl)ethyl)‐ solid; (185 mg, 87% yield); mp 149‐151 °C; 1H NMR (400 MHz,
2,3‐dihydro‐1H‐cyclo‐penta[b]quinoline‐2‐carboxylate
(6e). CDCl3) δ = 8.16 (s, 1H), 8.10 (d, J = 9.1 Hz, 1H), 7.98‐7.95 (m, 2H),
1
Colorless solid; (211 mg, 88 % yield); mp 163‐166 °C; H NMR (400 7.91 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.67 (t, J = 8.7 Hz, 1H), 7.61 (d, J
MHz, CDCl3) δ = 8.18 (s, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.96 (s, 1H), = 6.8 Hz, 2H), 7.47 (t, J = 8.4 Hz, 1H), 7.36 (t, J = 6.8 Hz, 2H), 7.31
7.88 (d, J = 8.4 Hz, 1H), 7.78‐7.76 (m, 1H), 7.73‐7.69 (m, 2H), 7.61‐ 7.29 (m, 1H), 7.10 (t, J = 8.4 Hz, 2H), 4.98 (t, J = 6.0 Hz, 1H), 3.65‐
7.59 (m, 2H), 7.53‐7.49 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.37‐7.35 3.59 (m, 1H), 3.57 (s, 3H), 3.39 (s, 3H), 3.38‐3.32 ppm (m, 1H); 13C
(m, 1H), 7.19‐7.17 (m, 1H), 4.68 (t, J = 5.3 Hz, 1H), 3.92‐3.85 (m, 2H), NMR (100 MHz, CDCl3) δ = 195.8, 169.5, 168.4, 159.4, 148.6, 136.4,
3.83‐3.73 (m, 2H), 1.00 ppm (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, 135.9, 135.7, 132.8, 132.7, 131.1, 130.9, 130.7, 130.6, 129.4, 129.1,
CDCl3) δ = 189.3, 166.7, 157.5, 149.0, 143.0. 135.1, 134.7, 134.6, 128.3, 128.2, 128.0, 127.7, 126.2, 115.8, 115.6, 66.3, 53.0, 52.3,
133.6, 133.0,131.4, 131.3, 129.9, 129.3, 129.2, 128.9, 128.4, 128.2, 45.4, 41.9 ppm; HRMS (ESI) m/z calcd for C31H24FNO5 (M+H)+
127.8, 126.7, 116.7, 63.3, 55.5, 46.0, 41.7, 13.4 ppm; HRMS (ESI) 510.1716, found 510.1710.
m/z calcd for C29H22N2O3S (M+H)+ 479.1429, found 479.1401.
(E)‐Dimethyl‐3‐benzylidene‐1‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐1H‐cyclop ‐
(Z)‐Dimethyl1‐benzylidene‐3‐(2‐oxo‐2‐phenylethyl)‐1H‐Inde ne‐ enta[b]quinoline‐2,2(3H)‐dicarboxylate (7f). Colorless solid; (196
1
2,2(3H)‐dicarbo xylate (7a). Pale Yellow solid; (189 mg, 86% yield); mg, 78% yield); mp 175.2‐178.1 °C. H NMR (400 MHz, CDCl3) δ =
1
mp 64‐67 °C; H NMR (400 MHz, CDCl3) δ = 7.87 (d, J = 8.2 Hz, 2H) 8.16 (s,1H), 8.10 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.84 (d, J = 7.6 Hz,
7.57 (d, J = 7.6 Hz, 1H), 7.52‐7.47 (m, 3H), 7.38 (t, J = 7.4 Hz, 2H), 2H), 7.73 (d, J = 7.6 Hz, 1H), 7.67 (t, J = 6.8 Hz, 1H), 7.62 (d, J = 8.4
7.31‐7.25 (m, 5H), 7.23‐7.27 (m, 2H), 4.97‐4.94 (m, 1H). 3.67 (s, 3H), Hz, 2H), 7.46 (t, J = 6.8 Hz, 1H), 7.37 (t, J = 8.4 Hz, 2H), 7.31‐7.29 (m,
3.60 (dd, J1 = 19.3, J2 = 9.1 Hz, 1H), 3.18‐3.12 ppm (m, 4H); 13C NMR 1H), 7.23 (d, J = 8.4 Hz, 2H), 4.99 (t, J = 6.8 Hz, 1H), 3.63‐3.59 (m,
(100 MHz, CDCl3) δ = 197.7, 170.2, 168.6, 144.3, 140.5, 139.0, 136.5, 1H), 3.57 (s, 3H), 3.41‐3.34 (m, 1H), 3.39 (s, 3H), 2.39 ppm (s, 3H);
130.2, 129.0, 128.4, 128.3, 127.9, 125.9, 124.0, 120.8, 67.8, 53.4, 13C NMR (100 MHz, CDCl3) δ = 197.0, 169.5, 168.4, 159.5, 148.6,
52.2, 47.9, 42.7 ppm; HRMS (ESI) m/z calcd for C28H25O5 (M+H)+ 144.2, 136.4, 136.2, 135.7, 133.9, 131.0, 129.3, 129.2, 129.2, 129.1,
441.1702, found 441.1723.
128.4, 128.1, 128.0, 127.8, 126.1, 66.3, 52.9, 52.5, 45.4, 41.8, 21.6
(Z)‐Dimethyl1‐benzylidene‐3‐(2‐(4‐fluorophenyl)‐2‐oxoethy )‐1H‐ ppm; HRMS (ESI) m/z calcd for C32H28NO5 (M+H)+ 506.1967, found
indene‐2,2(3H)‐dicarboxylate (7b). Pale Yellow solid; (186 mg, 81% 506.1973.
yield); mp 61‐63 °C; 1H NMR (400 MHz, CDCl3) δ = 7.92‐7.88 (m, 2H),
(Z)‐Diethyl‐1‐benzylidene‐5‐fluoro‐3‐(2‐oxo‐2‐phenylethyl)‐1,3‐
7.58 (d, J = 6.8 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.32‐7.28 (m, 4H), dihydro‐2H‐indene‐2,2‐dicarboxylate (7g). Yellow solid; (200mg,
1
7.24‐7.20 (m, 2H), 7.16‐7.13 (m, 1H), 7.05 (t, J = 8.0 Hz, 2H), 4.96‐ 87% yield); mp 78‐81 °C; H NMR (400 MHz, CDCl3) δ = 7.90 (d, J =
4.93 (m, 1H), 3.68 (s, 3H), 3.58 (dd, J1 = 19.0, J2 = 9.1 Hz, 1H), 3.16 (s, 9.6 Hz, 2H), 7.56‐7.51 (m, 4H), 7.41 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 6.8
3H), 3.10 ppm (dd, J1 = 18.3, J2 = 3.8 Hz, 1H); 13C NMR (100 MHz, Hz, 2H), 7.24‐7.22 (m, 1H), 7.18 (s, 1H), 7.00‐6.98 (m, 2H), 4.92 (t, J
CDCl3) δ = 196.2, 170.2, 168.7, 165.7 (d, J = 266.0 Hz), 144.2, 140.5, = 6.8 Hz, 1H), 4.16‐4.07 (m, 2H), 3.71‐3.67 (m, 1H), 3.62‐3.55 (m,
139.0, 136.2, 132.9, 130.6, 130.5, 129.0, 128.3, 128.0, 127.4, 126.1, 2H), 3.20 (dd, J1 = 19.1, J2 = 6.0 Hz, 1H), 1.17 (t, J = 6.8 Hz, 3H), 0.88
124.0, 120.8, 115.5 (d, J = 21.9 Hz), 67.8, 53.2, 52.3, 48.0, 42.7 ppm; ppm (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ = 197.2, 169.4,
HRMS (ESI) m/z calcd for C28H23FO5 (M+H)+ 459.1607, found 168.0, 163.3 (d, J = 245.9 Hz), 146.7 (d, J = 7.6 Hz), 137.6, 136.6,
459.1626.
136.3 (d, J = 13.3 Hz), 133.1, 128.6, 128.2, 128.0, 127.9, 127.9,
(Z)‐Dimethyl‐1‐benzylidene‐3‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐1H‐indene‐ 127.3, 125.5, 122.0 (d, J = 34.3 Hz), 115.1 (d, J = 23.8 Hz), 111.2 (d, J
2,2(3H)‐dicarb oxylate (7c). Pale Yellow solid; (182 mg, 80% yield);
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= 22.8 Hz), 68.3, 62.1, 61.7, 47.5, 42.2, 13.7, 13.3 ppm; HRMS (ESI)
m/z calcd for C30H31FO5 (M+H)+ 487.1921, found 487.1903.
Acknowledgements
We gratefully acknowledged the USIC, University of Delhi for
NMR, HRMS and X‐ray crystallography facility and DST & SERB
(SB/S1/OC‐38B/2013), Govt. of India, for providing funding and
fellowship to TC.
(E)‐Diethyl‐3‐benzylidene‐1‐(2‐oxo‐2‐(p‐tolyl)ethyl)‐1H‐cyclope‐
nta[b]quinoline‐2,2(3H)‐dicarboxylate (7h). Yellow solid; (210 mg,
77% yield); mp 62‐65 °C; 1H NMR (400 MHz, CDCl3) δ = 8.16 (s,1H),
8.09 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.73‐
7.70 (m, 3H), 7.66 (t, J = 6.8 Hz, 1H), 7.46 (t, J = 6.8 Hz, 1H), 7.38‐
7.34 (m, 2H), 7.31‐7.28 (m, 1H), 7.23 (d, J = 7.6 Hz, 2H), 4.95 (t, J =
7.6 Hz, 1H), 4.03‐4.39 (m, 2H), 3.95‐3.91 (m, 1H), 3.84‐3.8 (m, 1H),
3.60 (dd, J1 = 18.3, J2 = 6.0 Hz, 1H), 3.44 (dd, J1 = 18.3, J2 = 7.6 Hz,
1H), 2.39 (s, 3H), 1.03 (t, J = 7.6 Hz, 3H), 0.98 ppm (t, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ = 197.0, 169.0, 168.0, 157.7, 148.5,
144.2,136.4,136.1, 135.9, 133.9, 131.0, 130.9,129.6, 129.3, 129.2,
129.0, 128.4, 128.2, 128.1, 127.9, 127.8, 126.0, 66.5, 62.1, 61.9,
45.3, 41.7, 21.6, 13.6, 13.5 ppm; HRMS (ESI) m/z calcd for
C34H31NO5 (M+H)+ 534.2280, found 534.2320.
Notes and references
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malonate (8). Pale yellow oil; (182 mg, 80 % yield); H NMR (400
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MHz, CDCl3) δ = 7.83 (d, J = 8.4 Hz, 2H), 7.56‐7.54 (m, 2H), 7.50 (d, J
= 7.6 Hz, 1H), 7.36‐7.34 (m, 3H), 7.32‐7.30 (m, 1H), 7.23‐7.16 (m,
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The authors declare no conflict of interest.
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