An efficient synthesis of 4-arylquinolin-2(1 H)-ones and 3-alkenyl-4-arylquinolin-2(1 H)-one using a Pd/NiFe2O 4-catalyzed consecutive Heck reaction

Article abstract of DOI:10.1139/v11-103

A convenient one-pot method for the synthesis of 4-arylquinolin-2(1H)-ones and 4-arylcoumarins has been described. The successive Heck reaction on substituted 2-iodoaniline and 2-iodophenol catalyzed by a Pd/nickel ferrite catalyst followed by in situ cyc

Full text of DOI:10.1139/v11-103

1355
An efficient synthesis of 4-arylquinolin-2(1H)-ones
and 3-alkenyl-4-arylquinolin-2(1H)-one using a
Pd/NiFe2O4-catalyzed consecutive Heck reaction
Sanjay R. Borhade and Suresh B. Waghmode
Abstract: A convenient one-pot method for the synthesis of 4-arylquinolin-2(1H)-ones and 4-arylcoumarins has been de-
scribed. The successive Heck reaction on substituted 2-iodoaniline and 2-iodophenol catalyzed by a Pd/nickel ferrite catalyst
followed by in situ cyclization was the key step. The scope of this methodology was extended to the synthesis of bioactive
3-alkenyl derivatives of 4-arylquinolin-2(1H)-ones.
Key words: 4-arylquinolin-2(1H)-ones, Pd/nickel ferrite, Heck reaction, cross-coupling reactions, heterogeneous catalysis.
Résumé : On décrit une méthode monotope commode de synthèse des 4-arylquinoléin2(1H)-ones et 4-arylcoumarines.
L’étape clé est une réaction successive de Heck sur une 2-iodoaniline et le 2-iodophénol, catalysée de un catalyseur de
Pd/ferrite de nickel, suivie par une cyclisation in situ. On a étendu la portée de cette méthodologie à la synthèse de dérivés
3-alkényles biologiquement actifs des 4-arylquinoléin-2(1H)-ones.
Mots‐clés : 4-arylquinoléin-2(1H)-ones, Pd/ferrite de nickel, réaction de Heck, réactions de couplage croisé, catalyse hété-
rogène.
[Traduit par la Rédaction]
amino benzophenone or via closely related procedures.3c–3d
Introduction
However, starting materials used for the cyclization approach
are mostly amino ketones, which are not readily available;
furthermore, these procedures suffer from the disadvantage
that the aryl ring attached to the C-4 position of quinolinon-
2(1H)-ones has to be introduced very early in the overall syn-
thetic scheme, which limits the further laboration of this sub-
stituent.
Quinolin-2(1H)-ones constitute the basic structural frag-
ments of many natural and synthetic biologically active mol-
ecules. They shows antiviral, antineoplastic, anti-ischemic,
antiallergic, antihypertensive, and antiulcerative activity.1
Moreover, quinolin-2(1H)-ones also serve as valuable syn-
thetic intermediates because they can be easily transformed
into 2-substituted quinolines (e.g., 2-Cl, 2-OTf), which can
undergo further functionalization, such as nucleophillic aro-
matic substitutions and Pd-catalyzed coupling reactions.2
In particular, functionalized 4-aryl-quinolin-2(1H)-ones
(Fig. 1) are excellent inhibitors of acyl co-enzyme A and
cholesterol acyltransferase and are potent openers of high-
conductance calcium-activated K+ channels.3,4 They also
show potent antibacterial activity and inhibit the replication
of human immunodeficiency virus (HIV) induced by tumor
necrosis factor (TNF-a) with an IC50 of 2.5 µm.5 The deriva-
tives of 3-(quinolin-3-yl) acrylates 4 and the corresponding
reduced allylic alcohols have been identified by a group
from Bristol-Myers Squibb (BMS) as novel and potent maxi-
K channel openers useful for the treatment of male erectile
dysfunction.3a In addition, R 115777 (Zarnestra, 5), an orally
active antitumor agent, is currently undergoing human clini-
cal trials.3c–3d Although quinolinones exhibit a wide range of
biological activities, only a few methods for the synthesis of
4-arylquinolinon-2(1H)-ones are reported in the literature.6 In
most instances, an arylquinolin-2(1H)-one moiety was
achieved by acid–base catalyzed cyclization of N-acyl-o-
Several research groups have recently demonstrated the
successful use of a Pd-catalyzed C–C coupling reaction for
the synthesis of quinolin-2(1H)-one as a facile, versatile, and
practical route.7,8 Xu et al.8b reported a solid-phase protocol
(HypoGel Br resin) for the synthesis of 4-substituted quinoli-
nones using Pd-catalyzed Suzuki and Negishi cross-coupling
reactions in 63%–90% yield within 14 h. Cacchi and co-
workers8c–8d developed a methodology for the synthesis of 4-
aryl-quinolin-2(1H)-ones from 2-bromocinnamides and aryl
iodides through Heck reaction followed by an intramolecular
Buchwald–Hartwig amination sequence. In addition to this,
they also reported Heck reaction and in situ cyclization of
methyl b-(o-acetamidophenyl)acrylates with aryl iodides for the
synthesis of 4-aryl-quinolin-2(1H)-ones in the presence of Pd
(OAc)2 and KOAc in DMF at 120 °C.8g Kappe and co-workers8e
reported the synthesis of functionalized 4-aryl-quinolin-2(1H)-
ones by Suzuki coupling from 4-chloroquinoline-2(1H)-one
and boronic acid using a microwave. Although they reported a
good yield in a shorter reaction time, the use of a microwave
for industrial large-scale synthesis is not viable and also the
Received 27 March 2011. Accepted 29 May 2011. Published at www.nrcresearchpress.com/cjc on 7 October 2011.
S.R. Borhade and S.B. Waghmode. Department of Chemistry, University of Pune, Ganeshkhind, Pune 411 007, India.
Corresponding author: Suresh B. Waghmode (e-mail: suresh@chem.unipune.ac.in).
Can. J. Chem. 89: 1355–1363 (2011)
doi:10.1139/V11-103
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Can. J. Chem. Vol. 89, 2011
Fig. 1. Biologically active 4-arylquinolin-2(1H)-one derivatives.
required boronic acids are costly. More recently, Inamoto et
al.8a reported a synthetic approach through C–H bond func-
tionalization and intramolecular amidation sequencing in the
presence of a catalytic amount of PdCl2 and Cu(OAc)2 under
an O2 atmosphere. Although these authors have reported mod-
erate to good yields of 4-arylquinolin-2(1H)-ones, nonrecov-
ery of the precious palladium catalyst and Pd metal
contamination of the final products make these processes com-
mercially undesirable. Our ongoing interest is towards the de-
velopment of new catalyst system; recently, our group9a,9c,9d
and Manorama and co-workers9b reported the filtration-free
magnetically separable Pd/NiFe2O4 as an efficient and inex-
pensive catalyst for the Heck reaction. In light of this success-
ful methodology, we anticipated that the C–C bond formation
using the Heck reaction could lead to an efficient protocol for
the synthesis of 4-arylquinolin-2(1H)-ones. Herein we report
the novel use of Pd supported on nickel ferrite as a heteroge-
neous and recyclable catalyst for the synthesis of functional-
ized 4-arylquinolin-2(1H)-ones and 4-arylcoumarins in one
pot. We have also demonstrated the applicability of this
methodology for the synthesis of (2E)-ethyl-3-(4-(5-chloro-
2-methoxyphenyl)-6-(trifluoromethyl)-1,2-dihydro-1-methyl-
2-oxoquinolin-3-yl)acrylates in four steps.
poor yields (Table 1, entries 3 and 4). The presence of a
Pd(IV) oxidation state in the sodiumhexachloropalladate tet-
rahydrate (Na2PdCl6·4H2O) would not allow the catalyzation
of the Heck reaction (entry 7).
We conclude that the Pd sources having oxidation states
Pd(II) and Pd(0) were catalytically active for the Heck reac-
tion, whereas the Pd(IV) oxidation state was not active at all.
In comparison with homogeneous Pd(OAc)2, a slight increase
in the yield was observed for the Pd/NiFe2O4 catalyst (Ta-
ble 1, entries 2 and 8). Since it was easily separable from
the reaction mixture by applying an external magnetic field
and no product contamination with Pd metal was observed,
from this point forward Pd/NiFe2O4 catalyst was used unless
otherwise stated. Among the different bases studied, triethyl-
amine (TEA) and tributylamine (TBA) were found to be the
best (Table 1, entries 8 and 9). These organic bases were
superior to inorganic bases such as NaHCO3, NaOAc, and
Na2CO3 (Table 1, entries 8–12).
The effect of various solvents for consecutive Heck reac-
tion and in situ cyclization was studied and the results
showed that DMF and CH3CN gave 75% and 66% yield, re-
spectively, after 18 h, using TEA as a base. Nonpolar sol-
vents such as toluene and xylene were unproductive
(Table 1, entries 15 and 16). Temperature studies revealed
that 85 °C was enough to activate the Pd/NiFe2O4 catalyst
for the Heck reaction, whereas at higher temperature (100 °C),
a lower yield was observed. Various olefins such as methyl
acrylate, ethyl acrylate, butyl acrylate, and acrylic acid were
reacted with 4-(trifluoromethyl)-2-iodoaniline and it was
found that acrylic acid gave maximum yield.
Results and discussion
Initial studies were performed using 4-(trifluoromethyl)-2-
iodoaniline, acrylic acid, and iodobenzene to determine the
optimal reaction conditions. We examined various palladium
sources, solvents, bases, and temperatures and the results ob-
tained are summarized in Table 1. Amongst the different Pd
sources studied, palladium acetate (Pd(OAc)2), tetrakistriphen-
ylphosphine palladium(0) (Pd(PPh3)4), and tetraamminepal-
ladium(II) chloride (Pd(NH3)4Cl2·H2O) gave good to
moderate yields of corresponding 6-(trifluoromethyl)-4-
phenyl-2-quinolinone products (Table 1, entries 5 and 6). How-
ever, 1,1-bis(diphenylphophino)ferrocene–dichloropalladium
(PdCl2(dppf)) and palladium chloride (PdCl2) gave very
Using the optimized reaction conditions we explored the
general applicability of the Pd/NiFe2O4 catalyst for the con-
secutive Heck reaction of different 2-iodoanilines followed
by cyclization to yield corresponding 4-arylquinolin-2(1H)-
ones (Table 2). The transformation of various substituted
aryl iodides and bromides to corresponding 4-arylquinolin-2-
(1H)-one derivatives offered moderate to good yields. Aryl
iodides gave superior yields of the desired product as
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Borhade and Waghmode
Table 1. Optimization of the Heck coupling and cyclization conditions for the synthesis of 4-aryl-2-quinolin-
1357
2(1H)-one.
Entry
1
2
3
4
5
6
7
8
Pd source
—
Pd(OAc)2
PdCl2
PdCl2(dppf)
Pd(PPh3)4
Pd(NH3)4Cl2·H2O
Na2PdCl6·4H2O
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Pd/NiFe2O4
Base
TEA
TEA
TEA
TEA
TEA
TEA
TEA
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
DMSO
Xylene
Toluene
1,4-Dioxane
DMF
Temp. (°C)
85
85
85
85
85
85
85
85
85
85
85
85
85
85
85
85
Yielda
—
71
29
23
58
48
—
75
72
8
12
11
69
24
2
TEA
9
TBA
NaOAc
NaHCO3
Na2CO3
TEA
TEA
TEA
TEA
TEA
10
11
12
13
14
15
16
17
18
19
3
14
5
85
70
100
TEA
TEA
DMF
63
Note: Reaction conditions: 4-(trifluoromethyl)-2-iodoaniline (1.0 mmol), acrylic acid (1.05 mmol), Pd catalyst (2.5 mol %),
base (3.25 mmol), solvent (3.0 mL) and iodobenzene (1.25 mmol) added in a second step, time 18 h. TEA, triethylamine;
TBA, tributylamine.
aGC yields.
compared with aryl bromides. The less reactive chloroben-
zene and phenylboronic acid did not couple in the second
Heck reaction condition (Table 2, entries 11 and 12). The
aryl iodides reacted in the second Heck coupling reaction
with (E)-3-(2-amino-5-(trifluoromethyl)phenyl)acrylic acid
containing electron-donating methoxy groups at the ortho,
meta, or para positions produced the corresponding 4-aryl-
quinolin-2-(1H)-one compounds 10–12 in 59%, 61%, and
67% yields, respectively (Table 2, entries 4–6).
We also attempted the synthesis of a biologically active
flavonoid (4-aryl-2H-chromen-2-one, neoflavone),10 by a
similar route using 2-iodophenol and ethyl acrylates as start-
ing materials (Table 3).
solution was filtered to remove any dispersed particles. The
filtrate was concentrated and digested in the presence of
concd HNO3 + H2O2. The filtrate was then diluted to 50 mL
using a volumetric flask and analyzed by atomic absorption
spectroscopy (AAS) analysis. The Pd content detected in the
filtrate was only 2.1 ppm.
We believe that the present one-pot synthesis of 4-arylqui-
nolin-2(1H)-ones proceed via the pathway shown in
Scheme 1. The trans-2-aminocinnamic acid formed during
the first Heck reaction should not cyclize without first iso-
merizing.12 Oxidative addition of Pd to the aryl halide added
in the second step attached to an olefinic double bond of
trans-2-aminocinnamic acid and gave alkyl palladium species
21. Species 21 then underwent b-hydrogen elimination to
produce species 22, which generated product 7. Alternatively,
7 also could be formed by the route via intermediate 23 fol-
lowed by the b-hydrogen elimination.
The usefulness of our methodology was extended to the
synthesis of biologically important maxi-K channel opener 4
using the Pd/NiFe2O4-catalyzed Heck reaction. The synthesis
of 4 has been previously described by Hewawasam et al.3a in
2003 starting from N-Boc-protected 4-(trifluoromethyl)ani-
line, which involves more than 10 linear steps. The key step
in their synthesis was a base-catalyzed cyclization of an
appropriate N-acyl-O-aminobenzophenone precursor. Kappe
2-Iodophenol successfully reacted with ethyl acrylate and
gave 96% yield of the corresponding (E)-3-(2-hydroxy-
phenyl)acrylate, but the second Heck reaction with iodoben-
zene and in situ cyclization was ineffective. However, after
optimization of the reaction conditions we could achieve a
maximum yield of up to 31% of the corresponding 4-phenyl-
2H-chromen-2-one (Table 3, entry 1).
A hot filtration test11 was performed to investigate Pd
leaching into the reaction mixture. The test was done for the
4-(trifluoromethyl)-2-iodoaniline (Table 1, entry 8). After
18 h, the Pd/NiFe2O4 catalyst was removed from the hot re-
action mixture by applying an external magnet and the clear
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Can. J. Chem. Vol. 89, 2011
Table 2. One-pot synthesis of 4-aryl-2-quinolin-2(1H)-one derivatives.
Entry
1
2
3
4
5
6
7
8
R1
R2
H
X
I
I
I
I
I
I
Br
Br
I
Br
Cl
B(OH)2
I
I
I
Yielda
75
77
71
59
61
67
53
60
81
47
—
—
64
65
70
67
59
Product
7
8
4-CF3
4-CF3
4-CF3
4-CF3
4-CF3
4-CF3
4-CF3
4-CF3
H
H
H
H
H
4-CH3
3-CH3
2-OCH3
3-OCH3
4-OCH3
H
4-OCH3
H
H
9
10
11
12
7
12
13
13
13
13
14
15
16
17
16
9
10
11
12
13
14
15
16
17
H
H
3-OCH3
4-OMe
3-CH3
4-Me
4-OMe
H
H
H
H
I
Br
Note: Reaction conditions: substituted 2-iodoaniline (1.0 mmol), acrylic acid (1.05 mmol), triethylamine
(3.25 mmol), Pd/NiFe2O4 (2.5 mol %), aryl halide (1.25 mmol), and DMF (4.0 mL) at 85 °C with a time duration of
18 h.
aIsolated yields after column chromatography.
Table 3. One-pot synthesis of 4-aryl-2H-chromen-2-one derivatives.
Entry
R1
H
H
4-CH3
4-OCH3
X
I
Br
I
Yielda
31
13
24
28
Product
18
18
19
20
1
2
3
4
I
Note: Reaction conditions: 2-iodophenol (1.0 mmol), ethyl acrylate (1.05 mmol), triethylamine (3.25 mmol),
Pd/NiFe2O4 (2.5 mol %), aryl halide (1.25 mmol), DMF (4.0 mL), over 18 h of heating at 85 °C.
aIsolated yields after column chromatography.
and co-workers8e reported the synthesis of 4 from N,N-bis[4-
(trifluoromethyl)phenyl]malonide using Pd-catalyzed Suzuki
and Heck reactions assisted by microwave, which involves
six steps. Recently, Wu and co-workers8f also developed a
general synthetic methodology for the synthesis of 4 in a
combinatorial format starting from 3-bromo-4-trifloxy-quinolin-
2(1H)-one. Although there are reported methods for the
synthesis of 4, none of the reported methods is practical,
concise, or has a short synthetic route.
Our synthesis (Scheme 2) commenced with the consecutive
Heck reaction of 4-(trifluoromethyl)-2-iodoaniline (6) with
acrylic acid and 4-chloro-2-iodophenol was added in a second
step in DMF at 85 °C using Pd/NiFe2O4 as the catalyst in the
presence of TEA base. We observed the formation of the
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Borhade and Waghmode
1359
Scheme 1. Catalytic cycle for the consecutive Heck reaction and cyclization step.
desired product (24) in 75% yield. The N- and O-methylation
of 24 to 25 was carried out using methyl iodide in DMF at
room temperature in the presence of K2CO3 base. We intro-
duced the bromine moiety at the C-3 position of 25 by using
our photochemical reaction approach with N-bromosuccinamide
(NBS) in acetonitrile under UV irradiation.13 The required
3-bromo product (26) was obtained in 78% yield. Further
Heck vinylation of 3-bromoquinolinone (26) with ethyl
acrylate in the presence of 2.5 mol% Pd/NiFe2O4 catalyst
offered the target molecule 4 in its N-methyl-protected
form, but in very poor yield (12%). To improve the yield
of 4, we varied the palladium precursor. The reaction car-
ried out with Pd(OAc)2 gave only 26% yield. To further im-
prove the yield, the reaction was performed with Pd(PPh3)4
in an inert atmosphere, and this transformed into a 79%
yield of the product 4.14
for the synthesis of biologically active 3-alkenyl-4-aryl-2-
quinolinone from 4-(trifluoromethyl)-2-iodobenzamine in
four linear steps in an overall yield of 42.5%.
Experimental section
General methods
Unless otherwise stated, all experiments were performed in
an ambient atmosphere. All glasswares were acid and base
washed and oven-dried before use. The catalytic reactions
were carried out in 25 mL two-neck round-bottomed flasks
equipped with a reflux condenser in an air atmosphere. The
Pd salts/complexes, reactants, and solvents were obtained
from Sigma-Aldrich/Merck or Spectochem and used as re-
ceived without further purification or drying. The progress
of the reaction was monitored by gas chromatography (GC;
HP-5890, series II, equipped with a HP-5 capillary column
and an FID detector) and TLC. The products were isolated
by extractive work-up using ethyl acetate and were purified
using silica gel (100–200) column chromatography. The
products were characterized by GC–MS (Shimadzu QP-
5050, DB-5 column, and FID detector), FTIR (8400 Shi-
madzu), and NMR (Varian 300 MHz spectrometer in CDCl3
or DMSO-d6 with TMS as an internal standard) spectroscop-
ies. The Pd content was detected using an atomic absorption
spectrophotometer (AAS), model No. Chemito AA-201.
Conclusion
In summary, we have presented a practical useful one-pot
methodology for the synthesis of various 4-arylquinolin-
2(1H)-ones from 2-iodoanilines in good yields. The heteroge-
neous Pd/NiFe2O4 catalyst efficiently catalyzed the successive
Heck reaction in one pot and it could be easily separated
from the reaction mixture by applying an external magnetic
field. The scope of this methodology was successfully applied
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Can. J. Chem. Vol. 89, 2011
Scheme 2. Synthesis of the 3-alkenyl-4-aryl-2-quinolinone derivative.
General one-pot procedure for the synthesis of 4-
acrylate (1.5 mmol), triethylamine (3.25 mmol), and Pd/NiFe2O4
(2.5 mol %) in 4 mL of DMF solvent. The reaction mix-
tures were heated at 85 °C for 30 min. The reactions were
monitored by GC and TLC. The reaction mixture (0.25 mL)
was withdrawn by using a syringe, then diluted with water
(1.0 mL), and extracted with ethyl acetate (2 × 1.0 mL).
The ethyl acetate layer was separated, dried over sodium
sulfate, and analyzed by GC. After the complete conversion
of starting material, the new substrate, aryl halide
(1.25 mmol), was added and the reaction continued for a
further 16 h.
After the specified time of heating, the reaction mixture
was cooled to room temperature and the catalyst was sepa-
rated from the reaction mixture by applying an external mag-
net, and the clear solution was extracted with ethyl acetate
three times. The combined organic extracts were dried over
anhydrous Na2SO4 and solvent was evaporated under reduced
pressure. The crude product was then purified by silica gel
column chromatography (hexane – ethyl acetate, 7:3). Puri-
fied products were analyzed and characterized by GC, GC–
MS, IR, and NMR.
arylquinolin-2(1H)-ones (products 7–17)
To a 25 mL two-neck round-bottomed flask attached with
a reflux condenser were added 2-iodo-aniline (1 mmol),
acrylic acid (1.5 mmol), triethylamine (3.25 mmol), and Pd/
NiFe2O4 (2.5 mol %) in 4 mL of DMF solvent. The reaction
mixture was placed in a preheated oil bath at 85 °C for
30 min. The reactions were analyzed by GC and TLC. The
reaction mixture (0.25 mL) was withdrawn by using a sy-
ringe, then diluted with water (1.0 mL), and extracted with
ethyl acetate (1.0 mL). The ethyl acetate layer was separated,
dried over sodium sulfate, and analyzed by GC. After the
complete conversion of starting material, the new substrate,
aryl halide (1.25 mmol), was added and the reaction contin-
ued for a further 16 h.
After the specified time of heating, the reaction mixture was
cooled to room temperature and the catalyst was separated
from the reaction mixture by applying an external magnet, and
the clear solution was extracted with ethyl acetate (3 × 10 mL).
The combined organic extracts were dried over anhydrous
Na2SO4 and solvent was evaporated under reduced pressure.
The crude product was then purified by silica gel column chro-
matography (hexane – ethyl acetate, 7:3). All products were
analyzed and characterized by GC, GC–MS, IR, and NMR.
Synthesis of 4-(5-chloro-2-methoxyphenyl)-6-
(trifluoromethyl)-1-methylquinolin-2(1H)-one (25)
To a solution of 24 (0.34 g, 1.0 mmol) in DMF (4.0 mL)
were added methyl iodide (0.35 g, 2.2 mmol) and K2CO3
(0.44 g, 3.2 mmol) at ambient temperature. The reaction mix-
ture was stirred for 3 h at room temperature and then diluted
with ethyl acetate (3 × 20 mL). The organic layer was
General one-pot procedure for the synthesis of 4-aryl-2H-
chromen-2-ones (products 18–20)
To a 25 mL two-neck round-bottomed flask attached with
a reflux condenser were added 2-iodophenol (1 mmol), ethyl
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Borhade and Waghmode
1361
washed with water (2 × 10 mL) and brine (10 mL) and dried
over anhydrous Na2SO4. The solvent was evaporated under
reduced pressure, and the residue was purified by silica gel
column chromatography using hexane – ethyl acetate (1:4) as
the eluent to give 25 (0.36 g, 96% yield) as a white solid.
6-(Trifluoromethyl)-4-m-tolylquinolin-2(1H)-one (9)
FTIR (KBr, cm–1): 1105, 1577, 1614, 1668, 3005, 3404.
1H NMR (DMSO-d6) d: 2.50 (s, 3H) 6.61 (s, 1H), 7.37–7.47
(m, 3H), 7.56 (t, 1H) 7.68 (t, 1H) 7.96 (dd, 1H, J = 8.2 and
1.7 Hz), 12.35 (s, 1H). 13C NMR (DMSO-d6) d: 20.8, 116.9,
118.0, 121.8, 122.2, 122.5, 123.2(q), 125.6, 126.7, 128.6,
129.0, 129.7, 135.7, 138.3, 141.7, 151.0, 161.3. MS (EI): m/z
303 (M+). Anal. calcd for C17H12F3NO: C 67.32, H 3.99, N
4.62; found: C 67.32, H 4.08, N 4.62.
Synthesis of 3-bromo-4-(5-chloro-2-methoxyphenyl)-6-
(trifluoromethyl)-1-methyl quinolin-2(1H)-one (26)
A mixture of 25 (0.37 g, 1.0 mmol) and NBS (0.35 g,
2.0 mmol) was stirred in 4 mL of acetonitrile under an N2
atmosphere in the presence of a Philips HPL-N lamp
(250 W, kmax = 200–600 nm) fitted with a water circulation
arrangement at room temperature. After completion of the re-
action (monitored by TLC and GC), the reaction mixture was
quenched with cold water and extracted with ethyl acetate
(3 × 25 mL). The organic phase was washed with water and
brine, dried over anhydrous Na2SO4, and concentrated under
reduced pressure to afford the crude product, which was pu-
rified by column chromatography over silica gel (60–120
mesh) using ethyl acetate and petroleum ether (1:2) as the
eluent to give 26 (0.35 g, 78% yield) as a white solid.
6-(Trifluoromethyl)-4-(o-methoxyphenyl)quinolin-2(1H)-one
(10)
FTIR (neat, cm–1): 1070, 1371, 1494, 1579, 1658, 3306.
1H NMR (DMSO-d6) d: 3.72 (s, 3H), 6.97 (t, 1H, J =
7.4 Hz), 7.09 (d, 1H, J = 8.2 Hz), 7.27 (d, 1H, J = 7.4 Hz),
7.37 (t, 1H, J = 8.2 and 7.4 Hz), 7.47 (d, 1H, J = 8.5 Hz),
7.80 (d, 1H, J = 8.8 Hz), 7.90 (s, 1H), 8.13 (s, 1H), 12.17 (s,
1H). 13C NMR (DMSO-d6) d: 55.8, 111.3, 115.6, 118.8,
120.0, 121.9, 122.3 (q), 125.1, 125.3, 126.1, 129.5, 130.7,
132.3, 138.3, 140.8, 156.9, 160.8. MS (EI): m/z 319 (M+).
Anal. calcd for C17H12F3NO2: C 63.95, H 3.79, N 4.39;
found: C 63.97, H 3.88, N 4.62.
Synthesis of (2E)-ethyl 3-(4-(5-chloro-2-methoxyphenyl)-6-
(trifluoromethyl)-1,2-dihydro-1-methyl-2-oxoquinolin-3-yl)
acrylate (4)
6-(Trifluoromethyl)-4-(m-methoxyphenyl)quinolin-2(1H)-
one (11)
In an oven-dried 25 mL two-neck round-bottomed flask at-
tached with a reflux condenser were added 26 (0.44 g,
1.0 mmol), Pd(PPh3)4 (0.06 g, 5.0 mol%), ethyl acrylate
(0.30 g, 3.0 mmol), triethylamine (0.25 g, 2.5 mmol), and
5.0 mL of dry DMF. The reaction mixture was then heated
at 85 °C for 12 h. After the completion of reaction (moni-
tored by TLC), the heating was discontinued and the reaction
was quenched by adding ice-water (25 mL). The whitish pre-
cipitate was then extracted with ethyl acetate (3 × 25 mL).
The combined organic extracts was washed with brine
(30 mL), dried over Na2SO4, and solvent was evaporated
under reduced pressure. The crude product was purified by
silica gel (60–120 mesh) column chromatography using ethyl
acetate and petroleum ether (1:1) as the eluent to give 4
(0.37 g, 79% yield) as a white solid.
FTIR (KBr, cm–1): 1074, 1319, 1473, 1568, 1674, 3007,
1
3147. H NMR (DMSO-d6) d: 3.80 (s, 3H), 6.55 (s, 1H),
7.04–7.12 (m, 3H), 7.45–7.63 (m, 3H), 7.85 (d, 1H, J =
8.2 Hz), 12.24 (s, 1H). 13C NMR (DMSO-d6) d: 55.6, 114.5,
115.2, 117.3, 118.4, 121.2, 123.0(q), 123.7, 127.2, 130.4,
137.5, 142.2, 151.2, 159.9, 161.7. MS (EI): m/z 319 (M+).
Anal. calcd for C17H12F3NO2: C 63.95, H 3.79, N 4.39;
found: C 63.97, H 4.14, N 4.37.
6-(Trifluoromethyl)-4-(p-methoxyphenyl)quinolin-2(1H)-one
(12)
FTIR (KBr, cm–1): 1124, 1317, 1510, 1608, 1668, 2841,
1
3151. H NMR (DMSO-d6) d: 3.84 (s, 3H), 6.48 (s, 1H),
7.13 (d, 2H, J = 7.2 Hz), 7.45 (d, 2H, J = 7.2 Hz), 7.56 (d,
1H, J = 8.3 Hz), 7.67 (s, 1H), 7.86 (d, 1H, J = 8.6 Hz),
12.19 (s, 1H). 13C NMR (DMSO-d6) d: 55.1, 114.2, 116.8,
118.1, 121.7, 122.2, 123.1(q), 125.8, 126.7, 127.8, 130.0,
141.7, 150.6, 159.8, 161.2. MS (EI): m/z 319 (M+). Anal.
calcd for C17H12F3NO2: C 63.95, H 3.79, N 4.39; found: C
63.94, H 3.90, N 4.07.
Characterization data for all products
6-(Trifluoromethyl)-4-phenylquinolin-2(1H)-one (7)
FTIR (KBr, cm–1): 1265, 1475, 1573, 1685, 2918, 3315.
1H NMR (DMSO-d6) d: 6.51 (s, 1H), 7.47–7.57 (m, 7H),
7.83 (d, 1H, J = 9.8 Hz), 12.20 (s, 1H). 13C NMR (DMSO-
d6) d: 116.0, 116.9, 118.0, 122.6, 123.1(q), 126.8, 128.5,
128.8, 129.1, 135.7, 139.8, 141.7, 150.9, 161.2. MS (EI): m/z
289 (M+). Anal. calcd for C16H10F3NO: C 66.44, H 3.48, N
4.84; found: C 66.47, H 3.95, N 4.83.
4-Phenylquinolin-2(1H)-one (13, 5855-57-2)8a
FTIR (neat, cm–1): 1072, 1265, 1433, 1496, 1568, 1654,
1
3306. H NMR (DMSO-d6) d: 6.30 (s, 1H), 7.03–7.08 (m,
1H), 7.27–7.32 (m, 2H), 7.37–7.44 (m, 6H) 11.79 (s, 1H).
MS (EI): m/z 221 (M+).
6-(Trifluoromethyl)-4-p-tolylquinolin-2(1H)-one (8)
4-(3-Methoxyphenyl)quinolin-2(1H)-one (14, 65848-66-0)8a
FTIR (neat, cm–1): 1045, 1214, 1388, 1432, 1574, 1601,
1653, 2837, 3310. 1H NMR (DMSO-d6) d: 3.80 (s, 3H),
6.41 (s, 1H), 7.00–7.15 (m, 4H), 7.39–7.54 (m, 4H), 11.89
(s, 1H). MS (EI): m/z 251 (M+).
FTIR (KBr, cm–1): 1265, 1508, 1564, 1658, 3007, 3321.
1H NMR (DMSO-d6) d: 2.30 (s, 3H), 6.39 (s, 1H), 7.28 (s,
4H), 7.45 (d, 1H, J = 8.8 Hz), 7.52 (s, 1H), 7.76 (d, 1H,
J = 8.2 Hz), 12.11 (s, 1H). 13C NMR (DMSO-d6) d: 20.7,
116.8, 118.0, 122.4, 123.1(q), 125.0, 126.7, 128.4, 129.4,
132.8, 138.7, 141.7, 150.9, 161.2, 168.7. MS (EI): m/z 303
(M+). Anal. calcd for C17H12F3NO: C 67.32, H 3.99, N
4.62; found: C 67.33, H 4.10, N 4.63.
4-(4-Methoxyphenyl)quinolin-2(1H)-one (15, 37118-72-2)8a
FTIR (neat, cm–1): 1029, 1170, 1251, 1506, 1610, 1674,
2962, 3300.1H NMR (DMSO-d6): d 3.81 (s, 3H), 6.33 (s, 1H),
Published by NRC Research Press

1362
Can. J. Chem. Vol. 89, 2011
7.05–7.14 (m, 3H), 7.35–7.52 (m, 5H), 11.79 (s, 1H). MS
(EI): m/z 251 (M+).
1H), 7.29 (d, 1H, J = 8.8 Hz), 7.35 (d, 1H, J = 2.4 Hz),
7.58 (dd, 1H, J = 2.4 and 8.8 Hz), 7.84 (d, 1H, J =
8.8 Hz), 7.97 (d, 1H, J = 8.8 Hz). 13C NMR (DMSO-d6) d:
31.2, 56.0, 113.8, 116.7, 119.5, 121.0, 122.6, 123.0, 123.3
(q), 124.5, 126.1, 127.0, 129.1, 130.6, 140.7, 145.8, 154.5,
4-m-Tolylquinolin-2(1H)-one (16, 92909-30-4)8c
FTIR (neat, cm–1): 1038, 1160, 1271, 1385, 1432, 1547,
1
157.1. MS (EI): m/z 445 (M+), 447 (M+ + 2), 449 (M+
+
1606, 1654, 2836, 3316. H NMR (DMSO-d6) d: 2.36 (s,
3H), 6.34 (s, 1H), 7.08–7.13 (m, 1H), 7.20–7.41 (m, 7H),
4). Anal. calcd for C18H12BrClF3NO2: C 48.40, H 2.71, N
3.14; found: C 48.35, H 3.02, N 3.18.
11.85 (s, 1H). MS (EI): m/z 235 (M+).
4-p-Tolylquinolin-2(1H)-one (17, 106015-76-3)8c
(2E)-Ethyl-3-(4-(5-chloro-2-methoxyphenyl)-6-
(trifluoromethyl)-1,2-dihydro-1-methyl-2-oxoquinolin-3-yl)
acrylate (4)
FTIR (neat, cm–1): 1039, 1383, 1433, 1502, 1608, 1664,
1
2850, 3319. H NMR (DMSO-d6) d: 2.40 (s, 3H), 6.35 (s,
FTIR (neat, cm–1): 1132, 1286, 1371, 1494, 1620, 1662,
1695, 3111.1H NMR (CDCl3) d: 1.25 (t, 3H), 3.69 (s, 3H),
3.84 (s, 3H), 4.16 (q, 2H), 7.02 (d, 1H, J = 9.1 Hz), 7.08
(d, 1H, J = 2.4 Hz), 7.27 (s, 1H), 7.35 (d, 2H, J = 2.4 Hz),
7.58 (m, 2H), 7.80 (d, 1H, J = 9.1 Hz). 13C NMR (75 MHz,
CDCl3, TMS) d: 14.1, 30.1, 55.9, 60.3, 112.8, 114.8, 120.0,
124.1, 124.4, 125.1, 125.3, 125.4, 125.5, 126.1, 127.5(q),
130.1, 130.8, 137.4, 141.1, 147.0, 155.0, 160.4, 167.5. MS
(EI): m/z 465 (M+), 467 (M+ + 2). Anal. calcd for
C23H19ClF3NO4: C 59.30, H 4.11, N 3.01; found: C 59.29,
H 4.26, N 3.08.
1H), 7.13 (t, 1H, J = 7.7 and 7.9 Hz), 7.35–7.41 (m, 6H),
7.52 (t, 1H, J = 7.9 and 7.2 Hz), 11.82 (s, 1H). MS (EI): m/z
235 (M+).
4-Phenyl-2H-chromen-2-one (18, 15185-05-4)10
FTIR (neat, cm–1): 1365, 1444, 1491, 1560, 1606, 1734,
1
3072. H NMR (CDCl3) d: 6.36 (s, 1H), 7.22 (t, 1H, J =
7.7 Hz), 7.40–7.57 (m, 8H). MS (EI): m/z 222 (M+).
4-p-Tolyl-2H-chromen-2-one (19, 76103-24-7)10
FTIR (neat, cm–1): 1365, 1510, 1608, 1726, 3070. 1H
NMR (CDCl3) d: 2.45 (s, 3H), 6.36 (s, 1H), 7.20 (d, 1H,
J = 7.6 Hz), 7.23 (d, 1H, J = 7.6 Hz), 7.34 (m, 4H), 7.54
(m, 2H). MS (EI): m/z 236 (M+).
Acknowledgment
The authors are thankful to the Department of Science and
Technology (DST) and Council of Scientific and Industrial
Research (CSIR), New Delhi, India for their financial sup-
port.
4-(4-Methoxyphenyl)-2H-chromen-2-one (20, 170456-76-5)10
FTIR (neat, cm–1): 1294, 1599, 1491, 1670, 1757, 3072.1H
NMR (CDCl3) d: 3.90 (s, 3H), 6.36 (s, 1H), 7.05 (d, 2H, J =
8.5 Hz), 7.25 (t, 1H), 7.42 (m, 3H), 7.56 (t, 2H, J = 8.5 Hz).
MS (EI): m/z 252 (M+).
References
(1) (a) Gurjar, M. K.; Sharma, G. V. M.; Ilangovan, A.;
Narayanan, V. US Patent 6,191,279, 2001; (b) Thal, C.;
Boye, O.; Guenard, D.; Potier, P. Int. Patent WO 9002733,
1990; (c) Hewawasam, P.; Starrett, J. E., Jr.; Swartz, S. G. Int.
Patent WO 9909983, 1999; (d) Shogaki, T.; Toyoda, H.;
Kakita, T.; Furukawa, M.; Nakatsugi, S.; Masai, E.; Yashima,
T.; Ueda, I. Patent EP 577325, 1994; (e) Suzuki, K.; Fujiwara,
S.; Machii, D.; Ochifuji, N.; Takai, H.; Oono, T.; Furuta, S.;
Yamada, K. Patent JP 06092939, 1994; (f) Komatsu, M.;
Uchida, M.; Nishi, T.; Ishikawa, H.; Kuroda, T.; Tsuji, K.
Patent JP 08295673, 1996.
(2) (a) Goodell, J. R.; Puig Basagoiti, F.; Forshey, B. M.; Shi, P.
Y.; Ferguson, D. M. J. Med. Chem. 2006, 49 (6), 2127. doi:10.
1021/jm051229y; (b) Arcadi, A.; Cacchi, S.; Fabrizi, G.;
Manna, F.; Pace, P. Synlett 1998, 1998 (4), 446. doi:10.1055/s-
1998-1656; (c) Godard, A.; Fourquez, J. M.; Tamion, R.;
Marsais, F.; Queguiner, G. Synlett 1994, 1994 (4), 235. doi:10.
1055/s-1994-22807; (d) Anzini, M.; Cappelli, A.; Vomero, S.
J. Heterocycl. Chem. 1991, 28 (7), 1809. doi:10.1002/jhet.
5570280727.
(3) (a) Hewawasam, P.; Fan, W.; Ding, M.; Flint, K.; Cook, D.;
Goggins, G. D.; Myers, R. A.; Gribkoff, V. K.; Boissard, C.
G.; Dworetzky, S. I.; Starret, J. E.; Lodge, N. J. J. Med. Chem.
2003, 46 (14), 2819. doi:10.1021/jm030005h; (b) Cappelli, A.;
Pericot Mohr, G.; Gallelli, A.; Rizzo, M.; Anzini, M.; Vomero,
S.; Mennuni, L.; Ferrari, F.; Makovec, F.; Menziani, M. C.; De
Benedetti, P. G.; Giorgi, G. J. Med. Chem. 2004, 47 (10),
2574. doi:10.1021/jm031100t; (c) Angibaud, P. R.; Venet, M.
G.; Filliers, W.; Broeckx, R.; Ligny, Y. A.; Muller, P.;
Poncelet, V. S.; End, D. W. Eur. J. Org. Chem. 2004, 2004 (3),
479. doi:10.1002/ejoc.200300538; (d) Andresen, B. M.;
4-(5-Chloro-2-hydroxyphenyl)-6-(trifluoromethyl)quinolin-2
(1H)-one (24)
FTIR (neat, cm–1): 1437, 1558, 1653, 3311. 1H NMR
(DMSO-d6) d: 6.49 (s, 1H), 7.02 (d, 1H, J = 8.8 Hz), 7.30–
7.35 (m, 3H), 7.52 (d, 1H, J = 8.8 Hz), 7.81 (d, 1H, J =
8.5 Hz), 10.11 (s, 1H), 12.2 (s, 1H). 13C NMR (DMSO-d6)
d: 116.5, 117.3, 117.9, 121.6, 122.0, 122.8, 123.6(q), 124.6,
126.4, 126.5, 129.6, 130.1, 141.1, 147.9, 153.2, 161.4. MS
(EI): m/z 339 (M+) 341 (M++2). Anal. calcd for
C16H9ClF3NO2: C 56.57, H 2.67, N 4.12; found: C 56.59, H
2.87, N 4.17.
4-(5-Chloro-2-methoxyphenyl)-6-(trifluoromethyl)-1-
methylquinolin-2(1H)-one (25)
FTIR (neat, cm–1): 1305, 1494, 1602, 1674, 2845, 3055.1H
NMR (DMSO-d6) d: 3.68 (s, 3H), 3.71 (s, 3H), 6.66 (s, 1H),
7.24 (s, 1H), 7.27 (d, 1H, J = 7.0 Hz), 7.40 (d, 1H, J =
2.4 Hz), 7.58 (dd, 1H, J = 8.8 and 2.4 Hz), 7.79 (d, 1H,
J = 8.8 Hz), 7.94 (d, 1H, J = 8.8 Hz). 13C NMR (DMSO-
d6) d: 29.4, 55.8, 113.5, 116.4, 119.0, 122.9, 123.6, 124.7,
125.9, 126.8, 129.7, 130.5, 141.8, 146.1, 155.0, 160.5. MS
(EI): m/z 367 (M+), 369 (M+ + 2). Anal. calcd for
C18H13ClF3NO2: C 58.79, H 3.56, N 3.81; found: C 58.81,
H 3.68, N 3.81.
3-Bromo-4-(5-chloro-2-methoxyphenyl)-6-(trifluoromethyl)-
1-methylquinolin-2(1H)-one (26)
FTIR (neat, cm–1): 1120, 1311, 1491, 1654, 2848, 2941.
1H NMR (DMSO-d6) d: 3.36 (s, 3H), 3.81 (s, 3H), 7.19 (s,
Published by NRC Research Press

Borhade and Waghmode
1363
Couturier, M.; Cronin, B.; Docchio, M.; Ewing, M. D.; Guinn,
M.; Hawkins, J. M.; Jasys, V. J.; LaGreca, S. D.; Lyssikatos, J.
P.; Moraski, G.; Ng, K.; Raggon, J. W.; Stewart, A. M.;
Tickner, D. L.; Tucker, J. L.; Urban, F. J.; Vazquez, E.; Wei, L.
Org. Process Res. Dev. 2004, 8 (4), 643. doi:10.1021/
op049935g; (e) Hewawasam, P.; Fan, W.; Cook, D. A.;
Newberry, K. S.; Boissard, C. G.; Gribkoff, V. K.; Starrett, J.;
Lodge, N. J. Bioorg. Med. Chem. Lett. 2004, 14 (17), 4479.
doi:10.1016/j.bmcl.2004.06.051.
4039(03)00889-X; (j) Koltunov, K. Y.; Walspurger, S.;
Sommer, J. Chem. Commun. (Camb.) 2004, (15), 1754.
doi:10.1039/b404074k.
(7) (a) Pd-catalyzed synthesis of 2-quinolinones; see, for example,
Tadd, A. C.; Matsuno, A.; Fielding, M. R.; Willis, M. C. Org.
Lett. 2009, 11 (3), 583. doi:10.1021/ol802624e; (b) Liu, Z.;
Shi, C.; Chen, Y. Synlett 2008, (11), 1734; (c) Kadnikov, D.
V.; Larock, R. C. J. Org. Chem. 2004, 69 (20), 6772. doi:10.
1021/jo049149+; (d) Mori, M.; Chiba, K.; Ohta, N.; Ban, Y.
Heterocycles 1979, 13 (1), 329. doi:10.3987/S-1979-01-0329;
(e) Cortese, N. A.; Ziegler, C. B., Jr; Hrnjez, B. J.; Heck, R. F.
J. Org. Chem. 1978, 43 (15), 2952. doi:10.1021/jo00409a004.
(8) (a) Pd-catalyzed functionalizations of 2-quinolinones; see, for
example, Inamoto, K.; Saito, T.; Hiroya, K.; Doi, T. J. Org.
Chem. 2010, 75 (11), 3900. doi:10.1021/jo100557s; (b) Xu,
C.; Yang, L.; Bhandari, A.; Holmes, C. P. Tetrahedron Lett.
2006, 47 (28), 4885. doi:10.1016/j.tetlet.2006.05.032; (c)
Battistuzzi, G.; Bernini, R.; Cacchi, S.; De Salve, I.; Fabrizi,
G. Adv. Synth. Catal. 2007, 349 (3), 297. doi:10.1002/adsc.
200600342; (d) Bernini, R.; Cacchi, S.; Salve, I. D.; Fabrizi, G.
Synlett 2006, 18, 2947; (e) Glasnov, T. N.; Stadlbauer, W.;
Kappe, C. O. J. Org. Chem. 2005, 70 (10), 3864. doi:10.1021/
jo0502549; (f) Wang, Z.; Wang, B.; Wu, J. J. Comb. Chem.
2007, 9 (5), 811. doi:10.1021/cc7000937; (g) Bernini, R.;
Cacchi, S.; Fabrizi, G.; Sferrazza, A. Heterocycles 2006, 69
(1), 99. doi:10.3987/COM-06-S(O)30.
(4) (a) For recent papers, see Cheng, P.; Zhang, Q.; Ma, Y. B.;
Jiang, Z.-Y.; Zhang, X. M.; Zhang, F. X.; Chen, J. J. Bioorg.
Med. Chem. Lett. 2008, 18 (13), 3787. doi:10.1016/j.bmcl.
2008.05.065; (b) Capell, B. C.; Olive, M.; Erdos, M. R.; Cao,
K.; Faddah, D. A.; Tavarez, U. L.; Conneely, K. N.; Qu, X.;
San, H.; Ganesh, S. K.; Chen, X.; Avallone, H.; Kolodgie, F.
D.; Virmani, R.; Nabel, E. G.; Collins, F. S. Proc. Natl. Acad.
Sci. U.S.A. 2008, 105 (41), 15902. doi:10.1073/pnas.
0807840105; (c) Wall, M. J.; Chen, J.; Meegalla, S.;
Ballentine, S. K.; Wilson, K. J.; DesJarlais, R. L.; Schubert,
C.; Chaikin, M. A.; Crysler, C.; Petrounia, I. P.; Donatelli, R.
R.; Yurkow, E. J.; Boczon, L.; Mazzulla, M.; Player, M. R.;
Patch, R. J.; Manthey, C. L.; Molloy, C.; Tomczuk, B.; Illig, C.
R. Bioorg. Med. Chem. Lett. 2008, 18 (6), 2097. doi:10.1016/j.
bmcl.2008.01.088.
(5) (a) Kobayashi, Y.; Harayama, T. Org. Lett. 2009, 11 (7), 1603.
doi:10.1021/ol900255g; (b) Bracken, A.; Pocker, A.; Raistrick,
H. Biochem. J. 1954, 57, 587; (c) Mohammed, Y. S.; Luckner,
M. Tetrahedron Lett. 1963, 4 (28), 1953. doi:10.1016/S0040-
4039(01)90948-7; (d) Heguy, A.; Cai, P.; Meyn, P.; Houck, D.;
Russo, S.; Michitsch, R.; Pearce, C.; Katz, B.; Bringmann, G.;
Feineis, D.; Taylor, D. L.; Tyms, A. S. Antivir. Chem.
Chemother. 1998, 9, 149.
(6) (a) Huang, L.; Hsieh, M.; Teng, C.; Lee, K.; Kuo, S. Bioorg.
Med. Chem. 1998, 6 (10), 1657. doi:10.1016/S0968-0896(98)
00141-2; (b) Beier, N.; Labitzke, E.; Mederski, W. W. K. R.;
Radunz, H.-E.; Rauschenbach-Ruess, K.; Schneider, B.
Heterocycles 1994, 39 (1), 117. doi:10.3987/COM-93-S(B)5;
(c) Hauser, C. R.; Reynolds, G. A. J. Am. Chem. Soc. 1948, 70
(7), 2402. doi:10.1021/ja01187a025; (d) Staskun, B. J. Org.
Chem. 1964, 29 (5), 1153. doi:10.1021/jo01028a038; (e)
Koelsch, C. F.; Britain, J. W. J. Org. Chem. 1959, 24 (10),
1551. doi:10.1021/jo01092a041; (f) Kaslow, C. E.; Cook, D. J.
J. Am. Chem. Soc. 1945, 67 (11), 1969. doi:10.1021/
ja01227a032; (g) Hodgkinson, A. J.; Staskun, B. J. Org.
Chem. 1969, 34 (6), 1709. doi:10.1021/jo01258a039; (h) Park,
K. K.; Lee, J. J. Tetrahedron 2004, 60 (13), 2993. doi:10.1016/
j.tet.2004.02.001; (i) Wang, J.; Discordia, R. P.; Crispino, G.
A.; Li, J.; Grosso, J. A.; Polniaszek, R.; Truc, V. C.
Tetrahedron Lett. 2003, 44 (22), 4271. doi:10.1016/S0040-
(9) (a) Borhade, S. R.; Waghmode, S. B. Ind. J. Chem., Sect. B
2008, 47, 1549; (b) Baruwati, B.; Guin, D.; Manorama, S. V.
Org. Lett. 2007, 9 (26), 5377. doi:10.1021/ol702064x; (c)
Waghmode, S. B.; Wagholikar, S. G.; Sivasanker, S. Bull.
Chem. Soc. Jpn. 2003, 76 (10), 1989. doi:10.1246/bcsj.76.
1989; (d) Borhade, S. R.; Waghmode, S. B. Tetrahedron Lett.
2008, 49 (21), 3423. doi:10.1016/j.tetlet.2008.03.109.
(10) Yamamoto, Y.; Kirai, N. Org. Lett. 2008, 10 (24), 5513 and
references cited therein. doi:10.1021/ol802239n.
(11) Crudden, C. M.; Sateesh, M.; Lewis, R. J. Am. Chem. Soc.
2005, 127 (28), 10045. doi:10.1021/ja0430954.
(12) Horaguchi, T.; Hosokawa, N.; Tanemura, K.; Suzuki, T. J.
Heterocyclic Chem. 2002, 39 (1), 61. doi:10.1002/jhet.
5570390108.
(13) (a) Arbuj, S. S.; Waghmode, S. B.; Ramaswamy, A. V.
Tetrahedron Lett. 2007, 48 (8), 1411. doi:10.1016/j.tetlet.2006.
12.101; (b) Chhattise, P. K.; Ramaswamy, A. V.; Waghmode,
S. B. Tetrahedron Lett. 2008, 49 (1), 189. doi:10.1016/j.tetlet.
2007.10.126.
(14) Pd(PPh3)4 was freshly prepared and the reaction was conducted
in an inert atmosphere: Sunagawa, M.; Matsumura, H.;
Kitamura, Y. US Patent 5,226,186, 1993.
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