Buchwald-Hartwig coupling/Michael addition reactions: One-pot synthesis of 1,2-disubstituted 4-quinolones from chalcones and primary amines

Article abstract of DOI:10.1002/ejoc.201200172

The Buchwald-Hartwig coupling/Michael addition sequence has been successfully applied to the synthesis of functionalized 1,2-disubstituted 4-quinolones using Pd(OAc)₂ as a catalyst and PPh₃ as a ligand. Under these conditions, the intermediate products first formed from chalcones and primary amines underwent catalytic dehydrogenation to yield the 1,2-disubstituted 4-quinolones. Copyright

Full text of DOI:10.1002/ejoc.201200172

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:33
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201200172
Buchwald–Hartwig Coupling/Michael Addition Reactions: One-Pot Synthesis
of 1,2-Disubstituted 4-Quinolones from Chalcones and Primary Amines
Xiang-Dong Fei,[a] Zhou Zhou,[a] Wen Li,[a] Yong-Ming Zhu,*[a] and Jing-Kang Shen*[b]
Keywords: Palladium / Cyclization / Michael addition / Dehydrogenation / Heterocycles
The Buchwald–Hartwig coupling/Michael addition sequence
has been successfully applied to the synthesis of function-
alized 1,2-disubstituted 4-quinolones using Pd(OAc)2 as a
catalyst and PPh3 as a ligand. Under these conditions, the
intermediate products first formed from chalcones and pri-
mary amines underwent catalytic dehydrogenation to yield
the 1,2-disubstituted 4-quinolones.
Recently, the synthesis of 1,2-disubstituted 4-quinolones
has been reported by palladium-catalyzed tandem amin-
ation and copper-catalyzed cyclization.[20a,20b] However, the
deficiency is that the alkynone substrates were synthesized
from phenylacetylene by using nBuLi at –78 °C or
[PdCl2(PPh)3]/CuI as catalysts, which increases the diffi-
culty of substrate preparation (Scheme 1, a). On this basis,
we considered investigating a more general strategy for the
synthesis of 1,2-disubstituted 4-quinolones by using chalc-
ones as substrates, which can be easily obtained by aldol
condensation of the acetophenone with appropriate alde-
hydes (Scheme 1, b).
Introduction
Over the years, 4-quinolone derivatives have attracted
considerable attention from medicinal chemists due to their
diverse biological activity. They have been extensively
studied as a useful structural moiety for drug candidates.
Some of them have been investigated as antiviral,[1] antimi-
totic,[2] antidiabetic,[3] antibacterial,[4] antitrypanosomal,[4b]
and antitumor agents[5] as well as HIV-1 integrase inhibi-
tors.[6] In addition, scientists have found that quinolone de-
rivatives exhibit selective M1 positive allosteric modulating
activity.[7] Such characteristics have made the molecule im-
portant and this has resulted in sustained interest in de-
veloping new efficient synthetic strategies for this structural
moiety. Numerous synthetic routes to 4-quinolones have
been reported involving Camps cyclization,[8] reaction of is-
atoic anhydrides,[9–12] cyclization of N-substituted phenacyl
or acetonyl anthranilates in polyphosphoric acid,[13] cycliza-
tion of anthranilic acid derived ynone intermediates,[14] in-
tramolecular coupling of aryl halides with β-enaminones,[15]
acid-catalyzed cyclization,[16] cycloacylation of aniline de-
rivatives,[17] palladium-catalyzed carbonylative Sonogashira
coupling of 2-iodoaniline with arylacetylene,[18] and metal-
free intramolecular amination.[19] Although these methods
are effective and give relatively high yields, most of them
give 1-unsubstituted 2-substituted 4-quinolones, 1-unsubsti-
tuted 3-substituted 4-quinolones, or 1,3-disubstituted 4-
quinolones. Only a few literature reports give examples of
1,2-disubstituted 4-quinolone syntheses.
Scheme 1. Strategy for the synthesis of 1,2-disubstituted 4-quin-
olones.
Results and Discussion
During the course of our study we screened different
combinations of catalysts, solvents, and bases in an effort
to improve the yields. In an initial attempt, the reaction
was performed with Pd(OAc)2 as catalyst in the presence of
K2CO3 as base in anhydrous dioxane (Table 1, entry 1). The
product 3a was not observed. However, the expected prod-
uct 3a was formed in 74% yield when PPh3 was employed
as a ligand in the reaction (Table 1, entry 2). The yields
[a] School of Pharmacy, Soochow University,
Suzhou 215123, People’s Republic of China
E-mail: zhuyongming@suda.edu.cn
[b] Shanghai Institute of Materia Medica, Chinese Academy of
Sciences,
Shanghai 201203, People’s Republic of China
E-mail: jkshen@mail.shcnc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200172.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:33
Pages: 9
X.-D. Fei, Z. Zhou, W. Li, Y.-M. Zhu, J.-K. Shen
FULL PAPER
could not be improved by using other ligands such as PCy3, Table 2. Palladium-catalyzed reactions of 1a with primary
amines.[a]
DPPE, DPPF, and TFP (Table 1, entries 3–6). In compari-
son with K2CO3, the use of Cs2CO3 as base resulted in a
lower yield (Table 1, entry 7). The effect of solvent was then
explored, however, better results were not obtained with
other solvents (Table 1, entries 8–11). When [Pd2(dba)3] was
used as catalyst and combined with PPh3, the yield was
slightly lower (Table 1, entry 12). Thus, the best result was
obtained by using 1a and aniline in the presence of
Pd(OAc)2 (5 mol-%) and PPh3 (10 mol-%) in an-
hydrous dioxane (1 mL) with K2CO3 (2 equiv.) as base.
Table 1. Optimization of the reaction conditions for the synthesis
of 1,2-disubstituted 4-quinolones.[a]
Entry
Ligand
Solvent
Temperature Yield [%][b]
1
2
3
4
5
6
7
8
–
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
DMF
reflux
reflux
reflux
reflux
reflux
reflux
reflux
120 °C
reflux
120 °C
reflux
reflux
0
74
40
PPh3
PCy3
DPPE
DPPF
TFP
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
Ͻ5
Ͻ5
18
52[c]
0
9
toluene
DMSO
THF
61
9
10
11
12
31
dioxane
55[d]
[a] Conditions: 1a (0.5 mmol), aniline (2a; 0.75 mmol), Pd-
(OAc)2 (5 mol-%), ligand (10 mol-%), base (1.0 mmol), solvent
(1 mL), nitrogen. [b] Isolated yield. [c] Cs2CO3 was used as base.
[d] [Pd2(dba)3] was used as catalyst.
With the above optimized reaction conditions, we ex-
plored the substrate scope of the reaction. Interestingly,
attempts to expand the generality and applicability of the
reaction proved successful, thus providing a functional han-
dle for further manipulation. As illustrated in Table 2, 1a
readily reacted with functionalized arylamines bearing or-
tho, meta, and para substituents on the aryl ring to give the
corresponding products 3b–3l in moderate-to-good yields
(Table 2, entries 2–12). Arylamines containing electron-do-
nating groups (Table 2, entries 2–4, and 11) gave higher
yields than those with electron-withdrawing groups
(Table 2, entries 5–10). However, this reaction was not lim-
ited to simple aromatic amines; the pyridine-containing
substrate 2m also afforded 3m in good yield (Table 2, en-
try 13). Note also that aliphatic amines such as benzylamine
(2n) and cyclopropylamine (2o) gave products 3n and 3o,
respectively, in moderate yields (Table 2, entries 14 and 15).
Next, chalcones 1b–1m were investigated in the reaction
of aniline (2a) under the optimized conditions. Different
functional groups R1 and R2 of chalcone 1 were all toler-
ated (Table 3, entries 1–14). Note that the products 3y and
[a] All reactions were performed under N2 on a 0.5 mmol scale with
arylamines (1.5 equiv.), Pd(OAc)2 (5 mol-%), PPh3 (10 mol-%), and
K2CO3 (2.0 equiv.) in anhydrous 1,4-dioxane (1 mL) at reflux. [b]
Isolated yield.
2
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:33
Pages: 9
Buchwald–Hartwig Coupling/Michael Addition Reactions
Table 3. Palladium-catalyzed reactions of chalcones 1 with an- 3z were generated in moderate yields when R2 is an ali-
iline.[a]
phatic group (Table 3, entries 10 and 11). However, due to
the low oxidative addition reactivity of the C–Cl bond,
chloro-substituted substrate 1m gave product 3a in low yield
upon raised temperature (Table 3, entry 14).
A plausible reaction mechanism for this one-pot synthe-
sis of 1,2-disubstituted 4-quinolones is outlined in Scheme 2
(Paths A and B).[20b–20d] In Path A, oxidative addition of 1a
to the Pd0 catalyst leads to palladium complex A. The C=C
bond in A can be activated through coordination to the
PdII and attacked by aniline to form intermediate D. Note,
intermediate C was not formed from complex A under these
conditions. Path B involves the Michael addition of aniline
to 1a and oxidative addition, and then intermediate D is
formed by elimination of HBr. Both pathways proceed via
intermediate D, followed by reductive elimination of Pd0 to
yield E. Intermediate E leads to 3a by catalytic dehydroge-
nation of Pd0, which is the key step.[21]
Conclusions
We have developed an efficient palladium-catalyzed tan-
dem amination protocol for the synthesis of 1,2-disubsti-
tuted 4-quinolones from easily accessible chalcones and pri-
mary amines in which the catalyst palladium plays a dual
role, namely in the Buchwald–Hartwig coupling and cata-
lytic dehydrogenation. This approach provides one of the
simplest methods for the synthesis of this class of valuable
compounds, and a wide range of multisubstituted 4-quin-
olones could be generated accordingly in the construction
of a chemical library.
Experimental Section
General: Anhydrous dioxane was obtained by distillation over met-
allic sodium. Other solvents and reagents were used as received.
TLC was performed on silica HSGF254 plates. Melting points were
determined with a digital melting-point apparatus. 1H, 13C, and 19
F
NMR spectra were obtained from a solution in CDCl3 or DMSO
with TMS as internal standard using a 400/101/377 MHz (1H/13C/
19F) or 300/75 MHz (1H/13C) spectrometer. Chemical shifts (δ) are
given in ppm and J in Hz. IR spectra were recorded in KBr tablets
and wavenumbers are given in cm–1. HRMS were recorded by using
an electrospray ionization (ESI) mass spectrometer.
1-(2-Bromophenyl)-3-phenylprop-2-en-1-one (1a): Chalcones 1 were
prepared following the known procedure.[22] Benzaldehyde (1.061 g,
10 mmol) and NaOH (2.5 m, 80 mL) were added to a solution of o-
bromoacetophenone (1.991 g, 10 mmol) in EtOH (200 mL) at room
temp. The mixture was stirred for 3 h, neutralized with diluted HCl,
and extracted with EtOAc. The organic layer was dried (Na2SO4)
and the solvents evaporated. The residue was purified by column
chromatography on silica gel (EtOAc/petroleum ether = 1:50) to
give 1a as a yellow oil (2.613 g, 91%). 1H NMR (300 MHz,
CDCl3): δ = 7.65 (d, J = 7.8 Hz, 1 H), 7.60–7.49 (m, 2 H), 7.48–
7.28 (m, 7 H), 7.10 (d, J = 16.1 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 194.6, 146.6, 141.0, 134.3, 133.3, 131.3, 130.9, 129.1,
128.9, 128.5, 127.3, 126.0, 119.4 ppm.
[a] All reactions were performed under N2 on a 0.5 mmol scale with
arylamines (1.5 equiv.), Pd(OAc)2 (5 mol-%), PPh3 (10 mol-%), and
K2CO3 (2.0 equiv.) in anhydrous 1,4-dioxane (1 mL) at reflux. [b]
Isolated yield. [c] p-Methoxyaniline was used as a primary amine.
[d] m-Aminopyridine was used as a primary amine. [e] The reaction
temperature was 140 °C.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:33
Pages: 9
X.-D. Fei, Z. Zhou, W. Li, Y.-M. Zhu, J.-K. Shen
FULL PAPER
Scheme 2. Plausible mechanism for the synthesis of 3a from 1a.
1-(2-Bromophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (1b): Yel-
low solid (2.411 g, 76%); m.p. 88–90 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.51 (d, J = 8.6 Hz, 2 H),
7.44–7.28 (m, 4 H), 6.94 (dd, J = 15.3, 12.5 Hz, 3 H), 3.84 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.8, 161.9, 146.7,
141.3, 133.3, 131.1, 130.4, 129.0, 127.2, 127.0, 123.9, 119.4, 114.4,
55.4 ppm.
7.8 Hz, 1 H), 7.42–7.28 (m, 3 H), 6.62 (dd, J = 15.9, 6.6 Hz, 1 H),
6.39 (d, J = 16.0 Hz, 1 H), 2.30–2.14 (m, 1 H), 1.85–1.63 (m, 5 H),
1.34–1.13 (m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 195.7,
157.9, 141.1, 133.3, 131.0, 129.0, 127.7, 127.1, 119.3, 40.9, 31.5,
25.9, 25.6 ppm.
1-(2-Bromophenyl)-4,4-dimethylpent-2-en-1-one (1j): Yellow oil
(2.458 g, 92%). 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J =
7.8 Hz, 1 H), 7.40–7.25 (m, 3 H), 6.67 (d, J = 16.1 Hz, 1 H), 6.36
(d, J = 16.1 Hz, 1 H), 1.10 (s, 9 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 195.6, 162.1, 141.0, 133.2, 131.0, 128.9, 127.1, 125.3,
119.2, 34.1, 28.4 ppm.
1-(2-Bromophenyl)-3-(p-tolyl)prop-2-en-1-one (1c): Yellow solid
1
(2.560 g, 85%); m.p. 75–77 °C. H NMR (300 MHz, CDCl3): δ =
7.64 (d, J = 7.6 Hz, 1 H), 7.51–7.29 (m, 6 H), 7.20 (d, J = 7.7 Hz,
2 H), 7.05 (d, J = 16.1 Hz, 1 H), 2.38 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.8, 146.9, 141.6, 141.2, 133.4, 131.6,
131.2, 129.7, 129.1, 128.6, 127.3, 125.2, 119.5, 21.5 ppm.
1-(2-Bromo-5-fluorophenyl)-3-phenylprop-2-en-1-one (1k): Yellow
1
solid (1.343 g, 44%); m.p. 73–75 °C. H NMR (300 MHz, CDCl3):
δ = 7.65–7.49 (m, 3 H), 7.44 (d, J = 14.4 Hz, 4 H), 7.11 (ddd, J =
16.1, 8.7, 4.9 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
193.2, 163.3, 160.0, 147.2, 142.6, 142.6, 135.0, 134.9, 134.1, 131.1,
129.0, 128.7, 125.5, 118.8, 118.5, 116.5, 116.2, 113.7, 113.6 ppm.
1-(2-Bromophenyl)-3-(4-chlorophenyl)prop-2-en-1-one (1d): White
solid (1.897 g, 59%); m.p. 101–103 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.65 (d, J = 7.3 Hz, 1 H), 7.55–7.29 (m, 8 H), 7.07 (d,
J = 16.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.3,
144.8, 140.9, 136.8, 133.4, 132.9, 131.5, 129.7, 129.3, 129.2, 127.4,
126.5, 119.5 ppm.
1-(2-Bromo-5-methoxyphenyl)-3-phenylprop-2-en-1-one (1l): Yellow
solid (2.601 g, 82%); m.p. 110–112 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.56 (dd, J = 6.5, 3.0 Hz, 2 H), 7.50 (d, J = 8.8 Hz, 1
H), 7.45 (d, J = 16.1 Hz, 1 H), 7.40 (dd, J = 5.0, 1.8 Hz, 3 H), 7.08
(d, J = 16.1 Hz, 1 H), 6.95 (d, J = 3.0 Hz, 1 H), 6.88 (dd, J = 8.8,
3.1 Hz, 1 H), 3.81 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 194.4, 158.9, 146.6, 141.9, 134.4, 134.2, 130.9, 129.0, 128.6, 126.0,
117.6, 114.3, 109.7, 55.6 ppm.
1-(2-Bromophenyl)-3-(4-fluorophenyl)prop-2-en-1-one (1e): Yellow
1
oil (0.915 g, 30%). H NMR (300 MHz, CDCl3): δ = 7.64 (d, J =
7.5 Hz, 1 H), 7.54 (s, 2 H), 7.37 (dd, J = 17.8, 8.5 Hz, 4 H), 7.06
(dd, J = 22.5, 12.4 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 194.4, 165.9, 162.5, 145.1, 141.0, 133.4, 131.4, 130.5, 130.4, 129.1,
127.3, 125.8, 119.4, 116.3, 116.0 ppm.
1-(2-Chlorophenyl)-3-phenylprop-2-en-1-one (1m): Yellow oil
(1.966 g, 81%). 1H NMR (300 MHz, CDCl3): δ = 7.63–7.31 (m, 10
H), 7.15 (d, J = 16.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 193.7, 146.2, 139.0, 134.3, 131.3, 131.2, 130.8, 130.2, 129.2,
128.9, 128.5, 126.8, 126.2 ppm.
1-(2-Bromophenyl)-3-(3-nitrophenyl)prop-2-en-1-one (1f): Yellow so-
lid (1.561 g, 47%); m.p. 142–144 °C. 1H NMR (300 MHz, CDCl3):
δ = 8.40 (s, 1 H), 8.26 (d, J = 8.1 Hz, 1 H), 7.89 (d, J = 7.5 Hz, 1
H), 7.74–7.57 (m, 2 H), 7.56–7.33 (m, 4 H), 7.23 (d, J = 16.1 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.7, 148.6, 142.7,
140.5, 136.2, 133.9, 133.5, 131.9, 130.0, 129.3, 128.4, 127.5, 124.9,
122.8, 119.5 ppm.
General Procedure for the Synthesis of 1,2-Diphenylquinolin-4(1H)-
one (3a): Reactions were carried out under nitrogen. Aniline (2a;
0.75 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol), PPh3 (13.1 mg,
0.05 mmol), and K2CO3 (138.2 mg, 1.0 mmol) were added to an
oven-dried, nitrogen-purged flask containing 1a (0.5 mmol) in an-
hydrous 1,4-dioxane (1 mL). The reaction mixture was stirred un-
der reflux and monitored by TLC. Upon completion, the reaction
mixture was filtered and the residue was purified by column
chromatography on silica gel by using ethyl acetate/petroleum ether
(1:3) as eluent to afford pure product 3a as a yellow solid (109 mg,
1-(2-Bromophenyl)-3-(3-chlorophenyl)prop-2-en-1-one (1g): Yellow
1
solid (1.351 g, 42%); m.p. 54–56 °C. H NMR (300 MHz, CDCl3):
δ = 7.65 (d, J = 7.7 Hz, 1 H), 7.53 (s, 1 H), 7.47–7.28 (m, 7 H),
7.09 (d, J = 16.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
194.2, 144.5, 140.8, 136.2, 135.0, 133.4, 131.6, 130.6, 130.2, 129.2,
128.2, 127.4, 127.2, 126.6, 119.4 ppm.
1-(2-Bromophenyl)-3-(3-methoxyphenyl)prop-2-en-1-one (1h): Yel-
1
low oil (2.506 g, 79%). H NMR (300 MHz, CDCl3): δ = 7.64 (d,
1
74%); m.p. 281–283 °C. H NMR (400 MHz, CDCl3): δ = 8.51 (d,
J = 7.7 Hz, 1 H), 7.47–7.27 (m, 5 H), 7.11 (dd, J = 17.5, 9.0 Hz, 3
H), 6.96 (d, J = 7.7 Hz, 1 H), 3.82 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.6, 159.9, 146.5, 141.0, 135.7, 133.4,
131.3, 129.9, 129.1, 127.3, 126.3, 121.2, 119.4, 116.8, 113.2,
55.3 ppm.
J = 7.9 Hz, 1 H), 7.47 (t, J = 7.2 Hz, 1 H), 7.41–7.30 (m, 4 H),
7.20–7.15 (m, 7 H), 6.91 (d, J = 8.6 Hz, 1 H), 6.45 (s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 177.9, 154.0, 142.5, 139.0, 135.6,
131.8, 129.9, 129.5, 129.1, 128.9, 128.5, 127.8, 126.2, 126.0, 123.7,
118.0, 112.4 ppm. IR (KBr): ν = 1629, 1595, 1492, 1478, 1458,
˜
1-(2-Bromophenyl)-3-cyclohexylprop-2-en-1-one (1i): Yellow oil
1405, 1313, 1136, 700 cm–1. HRMS (ESI): calcd. for C21H16NO [M
(1.085 g, 37%). 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = + H]+ 298.1226; found 298.1235.
4
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:33
Pages: 9
Buchwald–Hartwig Coupling/Michael Addition Reactions
2-Phenyl-1-(p-tolyl)quinolin-4(1H)-one (3b): Yellow solid (135 mg,
87%); m.p. 210–212 °C. H NMR (300 MHz, CDCl3): δ = 8.51 (d,
HRMS (ESI): calcd. for C23H18NO2 [M + H]+ 340.1332; found
340.1342.
1
J = 7.9 Hz, 1 H), 7.46 (t, J = 7.0 Hz, 1 H), 7.36 (t, J = 7.4 Hz, 1
H), 7.24–7.10 (m, 7 H), 7.02 (d, J = 8.1 Hz, 2 H), 6.92 (d, J =
8.5 Hz, 1 H), 6.43 (s, 1 H), 2.33 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 177.9, 154.1, 142.7, 138.9, 136.4, 135.7, 131.8, 130.1,
129.6, 129.1, 128.5, 127.8, 126.2, 126.1, 123.7, 118.1, 112.5,
1-(4-Nitrophenyl)-2-phenylquinolin-4(1H)-one (3h): Yellow solid
(93 mg, 54%); m.p. 265–267 °C. H NMR (400 MHz, CDCl3): δ =
1
8.50 (d, J = 7.2 Hz, 1 H), 8.23 (d, J = 8.1 Hz, 2 H), 7.50 (t, J =
7.3 Hz, 1 H), 7.40 (t, J = 7.3 Hz, 3 H), 7.26–7.19 (m, 3 H), 7.16 (d,
J = 6.6 Hz, 2 H), 6.81 (d, J = 8.5 Hz, 1 H), 6.45 (s, 1 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 177.7, 153.0, 147.4, 144.8, 141.8,
134.8, 132.3, 131.4, 129.2, 129.0, 128.3, 126.6, 125.9, 124.9, 124.2,
21.1 ppm. IR (KBr): ν = 3051, 1628, 1599, 1514, 1464, 1415, 1319,
˜
835, 748, 700 cm–1. HRMS (ESI): calcd. for C22H18NO [M + H]+
312.1383; found 312.1395.
117.2, 113.0 ppm. IR (KBr): ν = 1630, 1601, 1592, 1518, 1493,
˜
1402, 1344, 1314, 756, 706 cm–1. HRMS (ESI): calcd. for
C21H15N2O3 [M + H]+ 343.1077; found 343.1090.
1-(4-Methoxyphenyl)-2-phenylquinolin-4(1H)-one (3c): Yellow solid
1
(129 mg, 79%); m.p. 193–195 °C. H NMR (300 MHz, CDCl3): δ
= 8.50 (d, J = 7.8 Hz, 1 H), 7.47 (t, J = 7.2 Hz, 1 H), 7.37 (t, J =
7.3 Hz, 1 H), 7.25–7.11 (m, 5 H), 7.06 (d, J = 8.7 Hz, 2 H), 6.93
(d, J = 8.5 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2 H), 6.43 (s, 1 H), 3.79
(s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 177.9, 159.4,
154.4, 142.9, 135.7, 131.8, 131.7, 130.8, 129.1, 128.5, 127.9, 126.1,
3-[4-Oxo-2-phenylquinolin-1(4H)-yl]benzonitrile (3i): Yellow solid
(98 mg, 61%); m.p. 262–264 °C. H NMR (300 MHz, CDCl3): δ =
1
8.46 (d, J = 7.9 Hz, 1 H), 7.64 (d, J = 7.3 Hz, 1 H), 7.57–7.44 (m,
4 H), 7.37 (t, J = 7.5 Hz, 1 H), 7.27–7.07 (m, 5 H), 6.78 (d, J =
8.5 Hz, 1 H), 6.39 (d, J = 6.8 Hz, 1 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 177.6, 153.2, 141.9, 140.0, 134.8, 133.5, 132.5, 132.2,
130.6, 129.0, 128.2, 126.4, 125.8, 124.1, 117.2, 117.0, 113.8,
126.0, 123.7, 118.1, 114.6, 112.4, 55.4 ppm. IR (KBr): ν = 1626,
˜
1599, 1508, 1462, 1406, 1252, 1028, 839, 758, 696 cm–1. HRMS
(ESI): calcd. for C22H18NO2 [M + H]+ 328.1332; found 328.1333.
112.8 ppm. IR (KBr): ν = 3040, 2230, 1629, 1601, 1481, 1466, 1416,
˜
1319, 748, 706 cm–1. HRMS (ESI): calcd. for C22H15N2O [M +
H]+ 323.1179; found 323.1195.
1-(Benzo[d][1,3]dioxol-5-yl)-2-phenylquinolin-4(1H)-one (3d): White
solid (140 mg, 82%); m.p. 188–190 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.50 (d, J = 8.0 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 1 H),
7.38 (t, J = 7.4 Hz, 1 H), 7.31–7.15 (m, 5 H), 7.00 (d, J = 8.6 Hz,
1 H), 6.74 (d, J = 8.5 Hz, 1 H), 6.62 (d, J = 5.7 Hz, 2 H), 6.43 (s,
1 H), 6.00 (d, J = 12.0 Hz, 2 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 177.9, 154.3, 148.5, 147.8, 142.9, 135.7, 132.7, 131.9,
129.1, 128.7, 128.0, 126.3, 123.8, 123.7, 118.0, 112.6, 110.5, 108.4,
2-Phenyl-1-[3-(phenylsulfonyl)phenyl]quinolin-4(1H)-one (3j): White
solid (131 mg, 60%); m.p. 336–338 °C. 1H NMR (400 MHz,
DMSO): δ = 8.29 (d, J = 7.5 Hz, 1 H), 8.17 (s, 1 H), 7.89 (d, J =
8.3 Hz, 1 H), 7.84 (d, J = 7.4 Hz, 2 H), 7.76 (t, J = 6.4 Hz, 2 H),
7.71–7.58 (m, 4 H), 7.45 (t, J = 7.4 Hz, 1 H), 7.19 (d, J = 7.3 Hz,
2 H), 7.05 (t, J = 7.5 Hz, 1 H), 6.95 (t, J = 7.5 Hz, 2 H), 6.79 (d,
J = 8.5 Hz, 1 H), 6.13 (s, 1 H) ppm. 13C NMR (101 MHz, DMSO):
δ = 176.1, 153.5, 142.2, 141.9, 140.4, 139.8, 135.4, 134.9, 133.8,
132.4, 131.1, 129.7, 129.6, 128.9, 128.3, 127.6, 127.3, 125.4, 125.3,
102.0 ppm. IR (KBr): ν = 1630, 1600, 1497, 1481, 1466, 1420, 1234,
˜
1038, 937, 748, 707 cm–1. HRMS (ESI): calcd. for C22H16NO3 [M
+ H]+ 342.1125; found 342.1140.
123.7, 117.8, 111.2 ppm. IR (KBr): ν = 3059, 1626, 1601, 1408,
˜
1-(4-Chlorophenyl)-2-phenylquinolin-4(1H)-one (3e): White solid
(126 mg, 76%); m.p. 204–206 °C. H NMR (400 MHz, CDCl3): δ
1320, 1304, 1155, 758, 707 cm–1. HRMS (ESI): calcd. for
C27H20NO3S [M + H]+ 438.1158; found 438.1175.
1
= 8.50 (dd, J = 8.0, 1.4 Hz, 1 H), 7.49 (ddd, J = 8.7, 7.1, 1.7 Hz,
1 H), 7.42–7.30 (m, 3 H), 7.26–7.19 (m, 3 H), 7.18–7.07 (m, 4 H),
6.87 (d, J = 8.5 Hz, 1 H), 6.44 (s, 1 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 177.8, 153.7, 142.3, 137.6, 135.3, 134.9, 132.0, 131.3,
129.8, 129.0, 128.8, 128.0, 126.3, 126.0, 123.9, 117.7, 112.7 ppm.
2-Phenyl-1-(m-tolyl)quinolin-4(1H)-one (3k): Yellow solid (122 mg,
1
79%); m.p. 222–224 °C. H NMR (300 MHz, CDCl3): δ = 8.51 (d,
J = 7.1 Hz, 1 H), 7.52–7.41 (m, 1 H), 7.36 (t, J = 7.4 Hz, 1 H),
7.25–7.09 (m, 7 H), 6.95 (t, J = 7.0 Hz, 3 H), 6.43 (s, 1 H), 2.28 (s,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 177.8, 153.9, 142.5,
139.6, 138.8, 135.6, 131.7, 130.3, 129.5, 129.2, 129.0, 128.5, 127.7,
IR (KBr): ν = 3030, 1618, 1599, 1493, 1463, 1408, 1317, 835, 762,
˜
702 cm–1. HRMS (ESI): calcd. for C21H15ClNO [M
332.0837; found 332.0850.
+
H]+
126.8, 126.0, 125.9, 123.6, 118.1, 112.3, 21.0 ppm. IR (KBr): ν =
˜
1629, 1595, 1478, 1460, 1406, 1307, 1136, 761, 708 cm–1. HRMS
(ESI): calcd. for C22H18NO [M + H]+ 312.1383; found 312.1398.
1-(4-Fluorophenyl)-2-phenylquinolin-4(1H)-one (3f): White solid
1
(104 mg, 66%); m.p. 220–222 °C. H NMR (300 MHz, CDCl3): δ
= 8.48 (dd, J = 8.0, 1.3 Hz, 1 H), 7.54–7.42 (m, 1 H), 7.37 (t, J =
7.1 Hz, 1 H), 7.26–7.11 (m, 7 H), 7.05 (t, J = 8.4 Hz, 2 H), 6.88 (d,
J = 8.6 Hz, 1 H), 6.41 (s, 1 H) ppm. 19F NMR (377 MHz, CDCl3):
δ = –111.0 (s, Ar-F) ppm. 13C NMR (101 MHz, CDCl3): δ = 177.8,
2-Phenyl-1-(o-tolyl)quinolin-4(1H)-one (3l): Red solid (51 mg, 33%);
m.p. 255–257 °C. H NMR (400 MHz, CDCl3): δ = 8.59–8.47 (m,
1 H), 7.52–7.45 (m, 1 H), 7.40 (t, J = 7.3 Hz, 1 H), 7.29–7.16 (m,
9 H), 6.77 (d, J = 8.5 Hz, 1 H), 6.49 (s, 1 H), 1.93 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 176.7, 154.0, 141.8, 137.9, 136.6,
135.3, 132.2, 131.5, 130.5, 129.5, 128.8, 127.8, 127.0, 126.4, 126.1,
1
1
163.3, 160.8 (d, JC-F = 186.75 Hz), 153.9, 142.5, 135.4, 135.0 (d,
3
4JC-F = 2.25 Hz), 132.0, 131.8, 131.7 (d, JC-F = 6.75 Hz), 129.1,
2
128.7, 128.0, 126.3, 126.0, 123.8, 117.7, 116.7, 116.5 (d, JC-F
=
123.9, 117.6, 112.7, 17.5 ppm. IR (KBr): ν = 1627, 1595, 1477,
˜
1460, 1406, 1310, 1138, 775, 760, 727, 702 cm–1. HRMS (ESI):
calcd. for C22H18NO [M + H]+ 312.1383; found 312.1397.
17.25 Hz), 112.6 ppm. IR (KBr): ν = 1622, 1595, 1506, 1480, 1464,
˜
1406, 1317, 1211, 1153, 838, 775, 708 cm–1. HRMS (ESI): calcd.
for C21H15FNO [M + H]+ 316.1132; found 316.1142.
2-Phenyl-1-(pyridin-3-yl)quinolin-4(1H)-one (3m): White solid
1
1-(4-Acetylphenyl)-2-phenylquinolin-4(1H)-one (3g): Yellow solid
(115 mg, 77%); m.p. 200–202 °C. H NMR (400 MHz, CDCl3): δ
1
(110 mg, 65%); m.p. 218–220 °C. H NMR (400 MHz, CDCl3): δ = 8.57 (dd, J = 4.7, 1.0 Hz, 1 H), 8.53–8.44 (m, 2 H), 7.57–7.46
= 8.51 (dd, J = 8.0, 1.5 Hz, 1 H), 7.95 (d, J = 8.5 Hz, 2 H), 7.47 (m, 2 H), 7.43–7.31 (m, 2 H), 7.25–7.19 (m, 3 H), 7.16 (dd, J = 6.5,
(ddd, J = 8.7, 7.1, 1.7 Hz, 1 H), 7.38 (t, J = 7.1 Hz, 1 H), 7.29 (d,
3.0 Hz, 2 H), 6.82 (d, J = 8.6 Hz, 1 H), 6.45 (s, 1 H) ppm. 13C
J = 8.5 Hz, 2 H), 7.25–7.12 (m, 5 H), 6.85 (d, J = 8.5 Hz, 1 H), NMR (101 MHz, CDCl3): δ = 177.8, 153.7, 150.9, 149.8, 142.4,
6.44 (s, 1 H), 2.59 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 196.6, 177.8, 153.4, 143.2, 142.1, 137.0, 135.2, 132.1, 130.4, 129.5,
129.0, 128.9, 128.1, 126.4, 126.0, 124.0, 117.6, 112.8, 26.7 ppm. IR
137.4, 136.0, 134.9, 132.3, 129.1, 129.0, 128.3, 126.6, 126.0, 124.2,
124.1, 117.4, 112.8 ppm. IR (KBr): ν = 3042, 1630, 1601, 1574,
˜
1482, 1414, 1319, 762, 748, 704 cm–1. HRMS (ESI): calcd. for
C20H15N2O [M + H]+ 299.1179; found 299.1184.
(KBr): ν = 1683, 1627, 1597, 1463, 1402, 1262, 762, 706 cm–1.
˜
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:34
Pages: 9
X.-D. Fei, Z. Zhou, W. Li, Y.-M. Zhu, J.-K. Shen
FULL PAPER
1-Benzyl-2-phenylquinolin-4(1H)-one (3n): Yellow solid (80 mg,
52%); m.p. 146–148 °C. H NMR (400 MHz, CDCl3): δ = 8.51 (d,
= 8.48 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 8.5 Hz, 1 H), 8.04 (s, 1
H), 7.55 (d, J = 7.4 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.45–7.29
(m, 5 H), 7.19 (d, J = 7.2 Hz, 2 H), 6.90 (d, J = 8.5 Hz, 1 H), 6.41
(s, 1 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 177.7, 151.0,
147.4, 142.5, 138.5, 137.1, 134.9, 132.3, 130.0, 129.8, 129.5, 129.2,
1
J = 7.3 Hz, 1 H), 7.55–7.48 (m, 1 H), 7.45–7.39 (m, 1 H), 7.39–
7.31 (m, 6 H), 7.31–7.21 (m, 3 H), 6.98 (d, J = 7.2 Hz, 2 H), 6.34
(s, 1 H), 5.27 (s, 2 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
177.6, 155.1, 141.2, 136.4, 135.7, 132.2, 129.6, 129.0, 128.6, 128.1,
127.6, 127.2, 126.8, 125.5, 123.7, 117.2, 113.1, 52.1 ppm. IR (KBr):
126.3, 126.0, 124.2, 123.5, 118.0, 112.7 ppm. IR (KBr): ν = 3056,
˜
3045, 1628, 1604, 1595, 1526, 1493, 1346, 841, 816, 744, 706 cm–1.
ν = 1615, 1596, 1556, 1486, 1413, 1269, 766, 735, 703 cm–1. HRMS HRMS (ESI): calcd. for C21H15N2O3 [M + H]+ 343.1077; found
˜
(ESI): calcd. for C22H18NO [M + H]+ 312.1383; found 312.1393.
343.1080.
1-Cyclopropyl-2-phenylquinolin-4(1H)-one (3o): Yellow solid
(59 mg, 45%); m.p. 168–170 °C. H NMR (400 MHz, CDCl3): δ =
2-(3-Chlorophenyl)-1-phenylquinolin-4(1H)-one (3u): White solid
(119 mg, 72%); m.p. 272–274 °C. H NMR (300 MHz, CDCl3): δ
1
1
8.43 (d, J = 7.9 Hz, 1 H), 7.96 (d, J = 8.6 Hz, 1 H), 7.69 (t, J =
7.6 Hz, 1 H), 7.53–7.47 (m, 5 H), 7.39 (t, J = 7.4 Hz, 1 H), 6.31 (s,
1 H), 3.42–3.27 (m, 1 H), 0.94 (d, J = 6.3 Hz, 2 H), 0.56 (d, J =
2.9 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 178.1, 155.4,
143.0, 136.8, 131.6, 129.1, 128.4, 128.3, 126.6, 126.3, 123.5, 117.8,
= 8.50 (d, J = 7.9 Hz, 1 H), 7.50–7.35 (m, 5 H), 7.17–7.08 (m, 5
H), 7.05 (d, J = 7.5 Hz, 1 H), 6.91 (d, J = 8.5 Hz, 1 H), 6.41 (s, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 177.8, 152.2, 142.5,
138.8, 137.2, 133.8, 132.0, 129.9, 129.7, 129.2, 128.8, 127.3, 126.3,
126.0, 123.9, 118.0, 112.5 ppm. IR (KBr): ν = 3042, 1627, 1595,
˜
1495, 1470, 1423, 1404, 1317, 800, 748 cm–1. HRMS (ESI): calcd.
for C21H15ClNO [M + H]+ 332.0837; found 332.0848.
113.2, 32.3, 12.9 ppm. IR (KBr): ν = 1613, 1594, 1555, 1486, 1462,
˜
1416, 777, 765, 707 cm–1. HRMS (ESI): calcd. for C18H16NO [M
+ H]+ 262.1226; found 262.1237.
2-(3-Methoxyphenyl)-1-phenylquinolin-4(1H)-one (3v): White solid
1
2-(4-Methoxyphenyl)-1-phenylquinolin-4(1H)-one (3p): White solid
(100 mg, 61%); m.p. 217–219 °C. H NMR (300 MHz, CDCl3): δ
1
(128 mg, 78%); m.p. 205–207 °C. H NMR (300 MHz, CDCl3): δ
= 8.50 (dd, J = 7.7, 1.2 Hz, 1 H), 7.53–7.31 (m, 5 H), 7.18 (d, J =
4.2 Hz, 2 H), 7.09 (t, J = 7.9 Hz, 1 H), 6.92 (d, J = 8.5 Hz, 1 H),
6.80–6.63 (m, 3 H), 6.45 (s, 1 H), 3.68 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 177.8, 158.8, 153.7, 142.5, 139.1, 136.7,
131.8, 129.9, 129.5, 128.9, 126.2, 126.0, 123.7, 121.7, 118.0, 114.7,
= 8.51 (d, J = 7.7 Hz, 1 H), 7.52–7.29 (m, 5 H), 7.16 (d, J = 6.5 Hz,
2 H), 7.08 (d, J = 7.9 Hz, 2 H), 6.90 (d, J = 8.4 Hz, 1 H), 6.69 (d,
J = 7.9 Hz, 2 H), 6.43 (s, 1 H), 3.74 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 177.9, 159.5, 153.9, 142.6, 139.2, 131.8,
130.5, 129.9, 129.6, 128.8, 128.0, 126.1, 125.9, 123.7, 118.0, 113.3,
114.4, 112.4, 55.2 ppm. IR (KBr): ν = 3051, 3037, 1627, 1602, 1595,
˜
1578, 1480, 1291, 1057, 748, 712 cm–1. HRMS (ESI): calcd. for
C22H18NO2 [M + H]+ 328.1332; found 328.1340.
112.6, 55.1 ppm. IR (KBr): ν = 3046, 1624, 1601, 1510, 1481, 1402,
˜
1250, 1186, 1024, 839, 776, 760 cm–1. HRMS (ESI): calcd. for
C22H18NO2 [M + H]+ 328.1332; found 328.1333.
2-(3-Methoxyphenyl)-1-(4-methoxyphenyl)quinolin-4(1H)-one (3w):
Yellow solid (134 mg, 75%); m.p. 178–180 °C. 1H NMR (300 MHz,
DMSO): δ = 8.26 (d, J = 7.8 Hz, 1 H), 7.59 (t, J = 6.9 Hz, 1 H),
7.42 (d, J = 7.1 Hz, 1 H), 7.34 (d, J = 8.3 Hz, 2 H), 7.17 (t, J =
7.7 Hz, 1 H), 7.05–6.73 (m, 6 H), 6.15 (s, 1 H), 3.74 (s, 3 H), 3.67
(s, 3 H) ppm. 13C NMR (75 MHz, DMSO): δ = 176.2, 159.1, 158.4,
154.3, 142.9, 137.0, 132.3, 131.6, 131.3, 129.1, 125.7, 125.3, 123.7,
121.5, 118.4, 114.9, 114.6, 114.5, 111.2, 55.5, 55.2 ppm. IR (KBr):
1-Phenyl-2-(p-tolyl)quinolin-4(1H)-one (3q): Yellow solid (133 mg,
86%); m.p. 289–291 °C. H NMR (300 MHz, CDCl3): δ = 8.50 (d,
J = 7.2 Hz, 1 H), 7.52–7.31 (m, 5 H), 7.16 (s, 2 H), 7.01 (d, J =
14.1 Hz, 4 H), 6.90 (d, J = 8.2 Hz, 1 H), 6.43 (s, 1 H), 2.25 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 177.8, 154.1, 142.5,
139.2, 138.5, 132.7, 131.7, 129.9, 129.5, 129.0, 128.8, 128.5, 126.1,
1
126.0, 123.6, 118.0, 112.5, 21.1 ppm. IR (KBr): ν = 1630, 1595,
˜
1508, 1493, 1478, 1458, 1403, 1313, 1136, 762, 706 cm–1. HRMS
(ESI): calcd. for C22H18NO [M + H]+ 312.1383; found 312.1397.
ν = 3056, 1626, 1597, 1508, 1463, 1407, 1250, 1032, 841, 760 cm–1.
˜
HRMS (ESI): calcd. for C23H20NO3 [M + H]+ 358.1438; found
358.1455.
2-(4-Chlorophenyl)-1-phenylquinolin-4(1H)-one (3r): White solid
1
(148 mg, 89%); m.p. 232–234 °C. H NMR (300 MHz, DMSO): δ
2-(3-Methoxyphenyl)-1-(pyridin-3-yl)quinolin-4(1H)-one (3x): White
solid (120 mg, 73%); m.p. 213–215 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.60 (s, 1 H), 8.49 (d, J = 7.8 Hz, 2 H), 7.58–7.48 (m,
2 H), 7.39–7.29 (m, 2 H), 7.12 (t, J = 6.8 Hz, 1 H), 6.84–6.71 (m,
4 H), 6.46 (s, 1 H), 3.70 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 177.8, 159.1, 153.5, 150.8, 149.8, 142.3, 137.4, 136.0, 132.3,
129.4, 126.5, 126.0, 124.1, 124.0, 121.6, 117.4, 114.8, 114.7, 112.7,
= 8.27 (d, J = 7.0 Hz, 1 H), 7.59 (t, J = 7.1 Hz, 1 H), 7.51–7.24
(m, 10 H), 6.83 (d, J = 8.5 Hz, 1 H), 6.16 (s, 1 H) ppm. 13C NMR
(75 MHz, DMSO): δ = 176.2, 152.9, 142.4, 138.8, 134.5, 133.5,
132.4, 131.2, 130.2, 129.8, 129.3, 127.9, 125.6, 125.4, 123.9, 118.3,
111.4 ppm. IR (KBr): ν = 3054, 1629, 1608, 1593, 1495, 1480, 1414,
˜
1316, 754, 696 cm–1. HRMS (ESI): calcd. for C21H15ClNO [M +
H]+ 332.0837; found 332.0853.
55.2 ppm. IR (KBr): ν = 1630, 1597, 1481, 1464, 1423, 1406, 1319,
˜
1292, 1267, 1039, 1028, 750 cm–1. HRMS (ESI): calcd. for
C21H17N2O2 [M + H]+ 329.1285; found 329.1292.
2-(4-Fluorophenyl)-1-phenylquinolin-4(1H)-one (3s): White solid
1
(121 mg, 77%); m.p. 225–227 °C. H NMR (300 MHz, DMSO): δ
= 8.28 (d, J = 6.8 Hz, 1 H), 7.60 (t, J = 7.0 Hz, 1 H), 7.42 (s, 8 H),
7.08 (t, J = 8.7 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 1 H), 6.16 (s, 1
2-Cyclohexyl-1-phenylquinolin-4(1H)-one (3y): Yellow solid (81 mg,
53%); m.p. 240–242 °C. H NMR (400 MHz, CDCl3): δ = 8.42 (d,
1
H) ppm. 19F NMR (377 MHz, CDCl3): δ = –111.8 (s, Ar-F) ppm.
J = 7.7 Hz, 1 H), 7.62 (s, 3 H), 7.37 (t, J = 7.6 Hz, 1 H), 7.29 (d,
J = 11.1 Hz, 3 H), 6.61 (d, J = 8.5 Hz, 1 H), 6.40 (s, 1 H), 2.11 (t,
J = 11.5 Hz, 1 H), 1.80 (d, J = 12.6 Hz, 2 H), 1.70 (d, J = 12.9 Hz,
2 H), 1.59 (d, J = 12.9 Hz, 1 H), 1.42 (q, J = 12.4 Hz, 2 H), 1.17
(q, J = 12.9 Hz, 1 H), 0.94 (q, J = 12.6 Hz, 2 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 178.2, 159.6, 142.6, 138.6, 131.3, 130.3,
129.7, 129.0, 125.8, 125.7, 123.3, 118.2, 108.2, 41.1, 33.0, 26.2,
1
13C NMR (75 MHz, DMSO): δ = 176.2, 163.5, 160.2 (d, JC-F
=
247.5 Hz), 153.1, 142.4, 138.9, 132.4, 132.1 (d, 4JC-F = 3 Hz), 131.7,
131.6 (d, JC-F = 8.25 Hz), 130.2, 129.7, 129.2, 125.6, 125.4, 123.8,
3
2
118.3, 115.0, 114.7 (d, JC-F = 21 Hz), 111.5 ppm. IR (KBr): ν =
˜
3045, 1628, 1595, 1511, 1494, 1483, 1420, 1319, 847, 747 cm–1.
HRMS (ESI): calcd. for C21H15FNO [M + H]+ 316.1132; found
316.1147.
25.5 ppm. IR (KBr): ν = 2940, 2847, 1626, 1601, 1489, 1465, 1423,
˜
2-(3-Nitrophenyl)-1-phenylquinolin-4(1H)-one (3t): Yellow solid 1303, 1136, 844, 781, 760, 710 cm–1. HRMS (ESI): calcd. for
1
(111 mg, 65%); m.p. 279–281 °C. H NMR (400 MHz, CDCl3): δ C21H22NO [M + H]+ 304.1696; found 304.1688.
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:34
Pages: 9
Buchwald–Hartwig Coupling/Michael Addition Reactions
Chem. Lett. 2003, 13, 2891–2893; b) S. Nakamura, M. Kozuka,
2-tert-Butyl-1-phenylquinolin-4(1H)-one (3z): Yellow solid (91 mg,
65%); m.p. 219–221 °C. H NMR (400 MHz, CDCl3): δ = 8.37 (d,
J = 7.6 Hz, 1 H), 7.56 (d, J = 6.4 Hz, 3 H), 7.40–7.18 (m, 4 H),
6.66 (s, 1 H), 6.40 (d, J = 8.7 Hz, 1 H), 1.16 (s, 9 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 178.8, 161.3, 144.8, 140.4, 131.6,
131.4, 129.8, 129.3, 125.4, 125.0, 123.2, 118.3, 110.1, 37.5,
1
K. F. Bastow, H. Tokuda, H. Nishino, M. Suzuki, J. Tatsuzaki,
S. L. M. Natschke, S.-C. Kuo, K.-H. Lee, Bioorg. Med. Chem.
2005, 13, 4396–4401; c) Q.-D. You, Z.-Y. Li, C.-H. Huang, Q.
Yang, X.-J. Wang, Q.-L. Guo, X.-G. Chen, X.-G. He, T.-K. Li,
J.-W. Chern, J. Med. Chem. 2009, 52, 5649–5661.
[6]
a) M. Sato, T. Motomura, H. Aramaki, T. Matsuda, M. Yama-
shita, Y. Ito, H. Kawakami, Y. Matsuzaki, W. Watanabe, K.
Yamataka, S. Ikeda, E. Kodama, M. Matsuoka, H. Shinkai, J.
Med. Chem. 2006, 49, 1506–1508; b) R. D. Santo, R. Costi, A.
Roux, M. Artico, A. Lavecchia, L. Marinelli, E. Novellino, L.
Palmisano, M. Andreotti, R. Amici, C. M. Galluzzo, L. Nen-
cioni, A. T. Palamara, Y. Pommier, C. Marchand, J. Med.
Chem. 2006, 49, 1939–1945; c) R. Dayam, L. Q. Al-Mawsawi,
Z. Zawahir, M. Witvrouw, Z. Debyser, N. Neamati, J. Med.
Chem. 2008, 51, 1136–1144; d) M. Sato, H. Kawakami, T. Mo-
tomura, H. Aramaki, T. Matsuda, M. Yamashita, Y. Ito, Y.
Matsuzaki, K. Yamataka, S. Ikeda, H. Shinkai, J. Med. Chem.
2009, 52, 4869–4882; e) Q.-Q. He, S.-X. Gu, J. Liu, H.-Q. Wua,
X. Zhang, L.-M. Yang, Y.-T. Zheng, F.-E. Chen, Bioorg. Med.
Chem. 2011, 19, 5039–5045.
F. V. Yang, W. D. Shipe, J. L. Bunda, M. B. Nolt, D. D. Wisno-
ski, Z. Zhao, J. C. Barrow, W. J. Ray, L. Mab, M. Wittmann,
M. A. Seager, K. A. Koeplinger, G. D. Hartman, C. W.
Lindsley, Bioorg. Med. Chem. Lett. 2010, 20, 531–536.
a) D. Ding, X. Li, X. Wang, Y. Du, J. Shen, Tetrahedron Lett.
2006, 47, 6997–6999; b) C. P. Jones, K. W. Anderson, S. L.
Buchwald, J. Org. Chem. 2007, 72, 7968–7973; c) J. Huang, Y.
Chen, A. O. King, M. Dilmeghani, R. D. Larsen, M. M. Faul,
Org. Lett. 2008, 10, 2609–2612.
a) P. Hradil, M. Grepl, J. Hlavácˇ, M. Soural, M. Malonˇ, V.
Bertolasi, J. Org. Chem. 2006, 71, 819–822; b) E. Stern, G. G.
Muccioli, B. Bosier, L. Hamtiaux, R. Millet, J. H. Poupaert,
J. P. Hénichart, P. Depreux, J.-F. Goossens, D. M. Lambert, J.
Med. Chem. 2007, 50, 5471–5484.
Y. Yoshino, T. Kurahashi, S. Matsubara, J. Am. Chem. Soc.
2009, 131, 7494–7495.
a) W. M. Abdou, A. A. Kamel, Synth. Commun. 2007, 37,
3945–3960; b) A. A. Kamel, W. M. Abdou, Synlett 2007, 1269–
1273.
31.7 ppm. IR (KBr): ν = 1623, 1560, 1571, 1488, 1464, 1391, 1315,
˜
847, 764, 715 cm–1. HRMS (ESI): calcd. for C21H14FNO [M +
H]+ 316.1132; found 316.1143. HRMS (ESI): calcd. for C19H20NO
[M + H]+ 278.1539; found 278.1532.
6-Fluoro-1,2-diphenylquinolin-4(1H)-one (3aa): Yellow solid (81 mg,
51%); m.p. 269–271 °C. 1H NMR (400 MHz, CDCl3): δ = 8.12 (dd,
J = 8.9, 3.0 Hz, 1 H), 7.40–7.32 (m, 3 H), 7.21–7.14 (m, 8 H), 6.90
(dd, J = 9.4, 4.3 Hz, 1 H), 6.40 (s, 1 H) ppm. 19F NMR (377 MHz,
CDCl3): δ = –117.8 (s, Ar-F) ppm. 13C NMR (75 MHz, CDCl3): δ
1
6
= 176.9, 160.8, 157.5 (d, JC-F = 244.5 Hz), 154.0, 139.0 (d, JC-F
4
= 4.5 Hz), 135.4, 129.8, 129.6 (d, JC-F = 14.25 Hz), 129.1, 128.6,
127.9, 127.5, 127.4 (d, JC-F = 6.75 Hz), 120.4, 120.1 (d, JC-F
18.75 Hz), 111.8, 110.8, 110.5 (d, JC-F = 22.5 Hz), 104.7 ppm. IR
5
3
=
2
[7]
[8]
(KBr): ν = 3046, 1616, 1595, 1496, 1478, 1395, 1310, 1182, 839,
˜
779, 704 cm–1. HRMS (ESI): calcd. for C21H15FNO [M + H]+
316.1132; found 316.1143.
6-Methoxy-1,2-diphenylquinolin-4(1H)-one (3ab): White solid
1
(67 mg, 41%); m.p. 244–246 °C. H NMR (400 MHz, CDCl3): δ =
7.90 (d, J = 3.0 Hz, 1 H), 7.39–7.29 (m, 3 H), 7.21–7.12 (m, 7 H),
7.09 (dd, J = 9.3, 3.1 Hz, 1 H), 6.85 (d, J = 9.3 Hz, 1 H), 6.42 (s,
1 H), 3.94 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 177.2,
156.3, 153.0, 139.3, 137.3, 135.7, 130.0, 129.5, 129.2, 128.9, 128.5,
[9]
127.8, 127.2, 122.5, 119.8, 111.6, 105.2, 55.8 ppm. IR (KBr): ν =
˜
1607, 1593, 1491, 1479, 1309, 1032, 779, 700 cm–1. HRMS (ESI):
calcd. for C22H18NO2 [M + H]+ 328.1332; found 328.1340.
[10]
[11]
Supporting Information (see footnote on the first page of this arti-
1
cle): H, 13C, and 19F NMR spectra.
[12]
S.-C. Kuo, H.-Z. Lee, J.-P. Juang, Y.-T. Lin, T.-S. Wu, J.-J.
Chang, D. Lednicer, K. D. Paull, C. M. Lin, E. Hamel, K.-H.
Lee, J. Med. Chem. 1993, 36, 1146–1156.
Acknowledgments
[13]
[14]
[15]
P. Hradil, J. Hlavac, K. Lemr, J. Heterocycl. Chem. 1999, 36,
We gratefully acknowledge the financial support by the Jiangsu
Higher Education Institutions (through PAPD, a project funded by
the Priority Academic Program Development) and the National
Nature Science Foundation of China (NSFC) (grant number
81172954).
141–144.
T. R. Ward, B. J. Turunen, T. Haack, B. Neuenswander, W.
Shadrick, G. Georg, Tetrahedron Lett. 2009, 50, 6494–6497.
a) R. Weiss, M. Bess, S. M. Huber, F. W. Heinemann, J. Am.
ˇ
ˇ
Chem. Soc. 2008, 130, 4610–4617; b) M. M. Skugor, V. Stimac,
ˇ
I. Palej, D. Lugaric´, H. C. Paljetak, D. Filic´, M. Modric´, I.
Dilovic´, D. Gembarovski, S. Mutak, V. E. Haber, D. J. Holmes,
[1] F. C. Santos, P. Abreu, H. C. Castro, I. C. P. P. Paixão, C. C.
Cirne-Santos, V. Giongo, J. E. Barbosa, B. R. Simonetti, V.
Garrido, D. C. Bou-Habib, D. O. Silva, P. N. Batalha, J. R. Te-
merozo, T. M. Souza, C. M. Nogueira, A. C. Cunha, C. R. Ro-
drigues, V. F. Ferreira, M. C. B. V. Souza, Bioorg. Med. Chem.
2009, 17, 5476–5481.
[2] a) M. Hadjeri, E.-L. Peiller, C. Beney, N. Deka, A. Lawson, C.
Dumontet, A. Boumendjel, J. Med. Chem. 2004, 47, 4964–
4970; b) Y.-Y. Lai, L.-J. Huang, K.-H. Lee, Z. Xiao, K. F. Bas-
tow, T. Yamoric, S.-C. Kuo, Bioorg. Med. Chem. 2005, 13, 265–
275.
[3] D. Edmont, R. Rocher, C. Plisson, J. Chenault, Bioorg. Med.
Chem. Lett. 2000, 10, 1831–1834.
[4] a) T. P. T. Cushnie, J. Lamb, Phytomedicine 2006, 13, 187–191;
b) X. Ma, W. Zhou, R. Brun, Bioorg. Med. Chem. Lett. 2009,
19, 986–989; c) A. A. Wube, F. Bucar, C. Hochfellner, M. Blun-
der, R. Bauer, A. Hüfner, Eur. J. Med. Chem. 2011, 46, 2091–
2101.
Z. Ivezic´-Schoenfeld, S. Alihodzic´, Bioorg. Med. Chem. 2010,
ˇ
18, 6547–6558; c) O. Tabarrini, S. Massari, D. Daelemans, F.
Meschini, G. Manfroni, L. Bottega, B. Gatto, M. Palumbo,
C. Pannecouque, V. Cecchetti, ChemMedChem 2010, 5, 1880–
1892.
[16]
a) J. A. Donnelly, D. F. Farrell, J. Org. Chem. 1990, 55, 1757–
1761; b) A. L. Tökés, G. Litkei, L. Szilágyi, Synth. Commun.
1992, 22, 2433–2445; c) C. Praveen, K. Parthasarathy, P. T. Per-
umal, Synlett 2010, 11, 1635–1640.
D. Zewge, C. Chen, C. Deer, P. G. Dormer, D. L. Hughes, J.
Org. Chem. 2007, 72, 4276–4279.
a) V. N. Kalinin, M. V. Sbostakovsky, A. B. Ponomaryov, Tetra-
hedron Lett. 1992, 33, 373–376; b) S. Torii, H. Okumoto, L. H.
Xu, M. Sadakane, M. V. Shostakovsky, A. B. Ponomaryov,
V. N. Kalinin, Tetrahedron 1993, 49, 6773–6784; c) N. Haddad,
J. Tan, V. Farina, J. Org. Chem. 2006, 71, 5031–5034; d) M.
Genelot, A. Bendjeriou, V. Dufaud, L. Djakovitch, Appl. Catal.
A 2009, 369, 125–132; e) M. Genelot, V. Dufaud, L. Djakov-
itch, Tetrahedron 2011, 67, 976–981.
[17]
[18]
[5] a) Y. Xia, Z.-Y. Yang, P. Xia, K. F. Bastow, Y. Nakanishi, P.
Nampoothiri, E. Hamel, A. Brossia, K.-H. Lee, Bioorg. Med.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:34
Pages: 9
X.-D. Fei, Z. Zhou, W. Li, Y.-M. Zhu, J.-K. Shen
FULL PAPER
[19] Q.-L. Liu, Q.-L. Li, X.-D. Fei, Y.-M. Zhu, ACS Comb. Sci.
2011, 13, 19–23.
[20] a) R. Bernini, S. Cacchi, G. Fabrizi, A. Sferrazza, Synthesis
2009, 1209–1219; b) T. Zhao, B. Xu, Org. Lett. 2010, 12, 212–
215; c) Z. Zheng, H. Alper, Org. Lett. 2008, 10, 829–832; d)
J. F. Hartwig, Angew. Chem. 1998, 110, 2154; Angew. Chem.
Int. Ed. 1998, 37, 2046–2067.
[21] a) Y. Shvo, A. H. I. Arisha, J. Org. Chem. 1998, 63, 5640–5642;
b) T. Ohmura, A. Kijima, M. Suginome, Org. Lett. 2011, 13,
1238–1241.
˙
[22] I. Karamana, H. Gezegen, M. B. Gürdere, A. Dingil, M. Cey-
lan, Chem. Biodiversity 2010, 7, 400–408.
Received: February 14, 2012
Published Online: ᭿
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20172
/KAP1
Date: 03-04-12 10:20:34
Pages: 9
Buchwald–Hartwig Coupling/Michael Addition Reactions
Catalytic Dehydrogenation
X.-D. Fei, Z. Zhou, W. Li, Y.-M. Zhu,*
J.-K. Shen* ....................................... 1–9
Buchwald–Hartwig Coupling/Michael Ad-
dition Reactions: One-Pot Synthesis of 1,2-
Disubstituted 4-Quinolones from Chalc-
ones and Primary Amines
The Buchwald–Hartwig coupling/Michael
addition sequence has been successfully
used for the synthesis of 1,2-disubstituted
4-quinolones starting from chalcones and
primary amines using Pd(OAc)2/PPh3/
K2CO3 as the catalyst system. The inter-
mediates formed underwent catalytic de-
hydrogenation to give the products in good
yields. The methodology has a broad scope
and is applicable to library synthesis.
Keywords: Palladium
/
Cyclization
/
/
Michael addition
Heterocycles
/ Dehydrogenation
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9