Palladium-catalyzed regioselective cross-coupling reactions of 3-bromo-4-tosyloxyquinolin-2(1H)-one with arylboronic acids. A facile and convenient route to 3,4-disubstituted quinolin-2(1H)-ones

Article abstract of DOI:10.1002/adsc.200700038

The palladium-catalyzed regioselective cross-coupling reaction of 3-bromo-4-tosyloxyquinolin-2(1H)-one with arylboronic acid is described, which provides a simple, general, efficient, and practical route for the synthesis of 3,4-disubstituted quinolin-2(1H)-ones.

Full text of DOI:10.1002/adsc.200700038

FULL PAPERS
DOI: 10.1002/adsc.200700038
Palladium-Catalyzed Regioselective Cross-Coupling Reactions of
3-Bromo-4-tosyloxyquinolin-2(1H)-one with Arylboronic Acids.
A Facile and Convenient Route to 3,4-Disubstituted
Quinolin-2(1H)-ones
Zhiyong Wang,a Renhua Fan,a and Jie Wua,b,*
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, Peopleꢀs Republic of China
Fax : (+86)-216-510-2412; e-mail: jie_wu@fudan.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, 354 Fenglin Road, Shanghai 200032, Peopleꢀs Republic of China
Received: January 22, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The palladium-catalyzed regioselective tical route for the synthesis of 3,4-disubstituted qui-
cross-coupling reaction of 3-bromo-4-tosyloxyquino- nolin-2(1H)-ones.
lin-2(1H)-one with arylboronic acid is described,
which provides a simple, general, efficient, and prac- Keywords: arylboronic acids; cross-coupling; homo-
geneous catalysis; palladium; quinolin-2(1H)-ones;
regioselectivity
Introduction
relevant heterocyclic compounds,[5] we became inter-
ested in the possibility of developing efficient meth-
High-throughput screening has created a critical ods for the synthesis of diversified quinolin-2(1H)-one
demand to develop practical routes for the rapid molecules which include four centers for the introduc-
chemical synthesis of natural product-like molecules. tion of diversity into the quinolin-2(1H)-one molecule
To secure such practice, the discovery and invention (Figure 1). Herein, we describe our recent efforts for
of new synthetic methods for accessing some natural the synthesis of 3,4-disubstituted quinolin-2(1H)-ones
product entities in more efficient ways has been a fer- via palladium-catalyzed regioselective cross-coupling
tile area of organic synthesis.[1] Although numerous reactions[6] of 3-bromo-4-tosyloxyquinolin-2(1H)-one
synthetic methods exists in the literature which allow with arylboronic acids.
the chemists to synthesize the intriguing molecules in-
Although there are classic methods for the genera-
dividually, nevertheless, it is highly desirable to devel- tion of a broad range of 3- or 4-substituted quinolin-
op even more effective synthetic methodologies for 2(1H)-ones,[7–9] the utility of these reactions for the
heterocycle formation in order to build up complex synthesis of 3,4-disubstituted quinolin-2(1H)-ones is
natural product-like molecules in a combinatorial quite limited.[10] On the other hand, several other
format.
methods including palladium-catalyzed reactions for
As a privileged fragment, the quinolin-2(1H)-one the synthesis of 3,4-disubstituted quinolin-2(1H)-ones
core is a ubiquitous subunit in many alkaloids with re- are usually complicated by low yields, harsh condi-
markable biological activities. Members of this family
have wide applications in medicinal chemistry, being
used as anticancer,[2] antiviral,[3] and antihypertensive
agents.[3] Moreover, quinolin-2(1H)-ones are also val-
uable intermediates in organic synthesis, since they
are easily converted into 2-chloro- and then 2-amino-
quinoline derivatives.[4] As part of a continuing effort
in our laboratory toward the development of new
methods for the expeditious synthesis of biologically Figure 1.
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1943

Zhiyong Wang et al.
FULL PAPERS
THF at room temperature. (Scheme 2) To our delight,
as expected we observed the formation of the desired
product 3a and 50% of isolated yield was obtained
after 12 h as well as recovery of the starting material.
The result was dramatically improved when the reac-
tion was performed at 608C (95% yield, 12 h). In this
reaction, only the 3-position was substituted and the
4-tosyloxy group was retained even in the presence of
3.0 equivs. of phenylboronic acid.
Scheme 1.
With this promising result in hand, we started to in-
tions, and limitations of substrate scope.[11–17] Thus, it vestigate the cross-coupling reactions between 3-
is of great interest to develop general protocols for bromo-4-tosyloxyquinolin-2(1H)-one 2 and various ar-
the synthesis of 3,4-disubstituted quinolin-2(1H)-ones ylboronic acids without optimization of the reaction
under mild reaction conditions.
conditions, and the results are shown in Table 1. From
Prompted by the recent advances in the halogena- Table 1, we found that this conditions allowed us to
tion of 1,3-dicarbonyl compounds,[18] we envisioned perform a broad range of cross-coupling reactions
that 3-bromo-4-hydroxyquinolin-2(1H)-one could be within 12 h. Thus, 2- or 4-methoxyphenylboronic acid
generated from commercially available 4-hydroxyqui- reacted with substrate 2 in the presence of PdCl2
nolin-2(1H)-one 1. This compound could be further
A
elaborated to afford 3-bromo-4-tosyloxyquinolin- water, 3.0 equivs.) in THF at 608C to give the cross-
2(1H)-one 2 after reaction with p-toluenesulfonyl coupling product 3b or 3c in 90% or 98% yield, re-
chloride in the presence of triethylamine (Scheme 1). spectively (entries 2 and 3, Table 1). Similarly, the re-
On the other hand, recently we found that the 4-tosyl- action of 2 with 4-methylphenylboronic acid furnished
oxy group attached to the electron-withdrawing a,b- the expected product 3d in 96% yield (entry 4).
unsaturated double bond increased its capability for
oxidative addition to transition metals[5] although are-
nesulfonates are relatively unreactive compared to
Table 1. Cross-coupling reactions between 3-bromo-4-tosyl-
oxyquinolin-2(1H)-one 2 and arylboronic acids.
the corresponding halides and triflates.[19] Based on
2
À
the results in which oxidative addition of the C
A
Br bond to the transition metal is easier than that of
2
À
the C
A
conceived that the regioselective cross-coupling of 3-
bromo-4-tosyloxyquinolin-2(1H)-one may be fulfilled
under suitable conditions. Due to their easy handling
and long shelf life, arylboronic acid derivatives would
be the starting materials of choice. Thus, we started to
explore the possibility of regioselective Suzuki–
Miyaura coupling reaction[20] by using 3-bromo-4-
tosyloxyquinolin-2(1H)-one 2 as an electrophile for
the synthesis of 3,4-disubstituted quinolin-2(1H)-ones.
Entry
R1
Product
Yield [%][a]
1
2
3
4
5
6
7
8
9
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
95
90
98
96
88
95
62
55
90
2-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-CF3C6H4
3-CF3C6H4
4-NCC6H4
3-NCC6H4
4-AcC6H4
Results and Discussion
Our studies commenced with the reaction of 3-
bromo-4-tosyloxyquinolin-2(1H)-one 2 with phenyl-
[a]
Isolated yield based on 3-bromo-4-tosyloxyquinolin-
boronic acid catalyzed by PdCl
A
2(1H)-one 2.
Scheme 2.
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A Facile and Convenient Route to 3,4-Disubstituted Quinolin-2(1H)-ones
FULL PAPERS
Table 2. Reaction of compound 3a with 4-methoxyphenylboronic acid under various conditions.
Entry
[Pd]
PdCl2
L
Base
Solvent
T [8C]
Yield [%][a]
1
2
3
4
5
6
7
8
(PPh3)2
-
-
-
-
-
A
A
B
KF
KF
KF
KF
Na2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
t-BuOK
THF
THF
60
60
100
110
110
60
80
80
80
80
n.r.
n.r.
n.r.
n.r.
n.r.
50
Pd(PPh3)4
Pd(PPh3)4
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
G
T
dioxane
toluene
toluene
THF
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
U
R
A
G
84
N
trace
n.r.
trace
trace
trace
15
9
U
C
10
11
12
13
U
PCy3
dppp
dppf
D
E
80
80
80
G
U
[a]
Isolated yield based on substrate 3a.
Cross-coupling of 3- or 4-trifluoromethylphenylboron- butyl alcohol and increasing the temperature to 808C
ic acid with 2 provided the desired products in 95% improved the result (84% yield, entry 7). However,
or 88% yield (entries 5 and 6). Arylboronic acids reduced reactivity and inferior results were displayed
bearing a ketone function are compatible with the when other ligands were employed in the reaction
mild cross-coupling conditions, and 4-acetylphenylbor- (Table 2, entries 8–13). For example, only a 15% yield
onic acid reacted smoothly with 2 leading to the of 4a was obtained when the precusor D of a N-hetero-
ketone 3i in 90% yield (entry 9). 3- or 4-cyanophenyl- cyclic carbene was utilized as ligand.
boronic acid reacted with 2 within 12 h affording the
expected product in moderate yield (entries 7 and 8). next investigated the scope of this reaction under the
After introducing diversity in 3-position, we consid- optimized conditions [t-BuOH, 5 mol% of Pd(OAc)2,
To demonstrate the generality of this method, we
AHCTREUNG
ered the further elaboration of compound 3 for reali- 10 mol% of Ligand A, K3PO4, 808C) and the results
zation the cross-coupling of 4-position. Substrates 3a are summarized in Table 3. As shown in Table 3, this
and 4-methoxyphenylboronic acid were selected for method is equally effective for both substrate 3 and
the model studies. As mentioned above, no reaction arylboronic acids. 3,4-Disubstituted quinolin-2(1H)-
occurred under the conditions shown in Table 1. ones 4 were generated successfully in good yields.
Screening the palladium catalyst, base, solvent, and When 3-phenyl-4-tosyloxyquinolin-2(1H)-one 3a was
temperature also gave disappointing results. (Table 2, employed as substrate, a better result was generated
entries 1–5) We next screened this reaction with vari- for arylboronic acids attached to electron-donating
ous ligands such as phosphines, diphosphines, and N- groups. For examples, reaction of compound 3a with
heterocyclic carbenes (Table 2, entries 6–13). Gratify- 4-methoxyphenylboronic acid afforded the desired
ingly, expected product 4a (50% yield) was generated product 4a in 84% yield (Table 3, entry 1), while
when the reaction was performed in the presence of 70% yield of 4c was obtained when 3-trifluorome-
palladium acetate (5 mol%), ligand A, and K3PO4 in thylphenylboronic acid was used as the partner
THF at 608C (entry 6). Changing the solvent to tert- (Table 3, entry 3). For substrate 3 with different elec-
Adv. Synth. Catal. 2007, 349, 1943 – 1948
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Zhiyong Wang et al.
FULL PAPERS
Table 3. Synthesis of 3,4-disubstituted quinolin-2(1H)-ones.
Experimental Section
General Procedure for the Cross-Coupling Reaction
between 3-Bromo-4-tosyloxyquinolin-2(1H)-one 2
and Arylboronic Acids
To a mixture of 3-bromo-4-tosyloxy-quinolin-2(1H)-one 2
(81.4 mg, 0.20 mmol), PdCl2(PPh3)2 (7.0 mg, 0.01 mmol), and
A
Entry R1
R2
Product Yield [%][a]
boronic acid (1.5 equivs.) in THF (2 mL) was added potassi-
um carbonate (2.0M in water, 0.3 mL) under a nitrogen at-
mosphere. The reaction mixture was stirred at 608C over-
night. Following completion of the reaction as monitored by
TLC, the reaction mixture was diluted with ethyl acetate
(20 mL) and separated. The solution was dried and filtered,
and the filtrate was concentrated to a residue which was pu-
rified by flash chromatography [silica gel, 2/1 (v/v) hexane/
ethyl acetate] to give the corresponding product 3.
1-Methyl-2-oxo-3-phenyl-1,2-dihydroquinolin-4-yl 4-meth-
ylbenzenesulfonate (3a):[21] 1H NMR (400 MHz, CDCl3): d=
8.15 (d, J=7.8 Hz, 1H), 7.66 (t, J=7.3 Hz, 1H), 7.43 (d, J=
8.2 Hz, 1H), 7.36 (t, J=7.3 Hz, 1H), 7.25–7.16 (m, 8H), 7.03
(d, J=7.8 Hz, 1H), 3.77 (s, 3H), 2.39 (s, 3H).
3-(2-Methoxyphenyl)-1-methyl-2-oxo-1,2-dihydroquinolin-
4-yl 4-methylbenzenesulfonate (3b): 1H NMR (400 MHz,
CDCl3): d=(ppm) 8.12 (d, J=7.8 Hz, 1H), 7.63 (t, J=
7.3 Hz, 1H), 7.41 (d, J=8.2 Hz, 1H), 7.33 (t, J=7.3 Hz,
1H), 7.28–7.12 (m, 5H), 7.07 (d, J=7.8 Hz, 2H), 6.85 (t, J=
7.3 Hz, 1H), 6.69 (d, J=8.2 Hz, 1H), 3.75 (s, 3H), 3.62 (s,
3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): d=161.9,
157.1, 151.3, 144.6, 139.3, 133.4, 132.0, 131.3, 129.5, 129.3,
127.5, 125.4, 122.9, 122.3, 121.2, 120.1, 117.6, 113.9, 111.0,
55.5, 30.2, 21.6; MS: m/z (M+ +1)=436, calcd.: 436; HR-
MS: m/z=435.1145, calcd. for C24H21NO5S:
3-(4-Methoxyphenyl)-1-methyl-2-oxo-1,2-dihydroquinolin-
4-yl 4-methylbenzenesulfonate (3c): 1H NMR (400 MHz,
CDCl3): d=8.15 (d, J=7.8 Hz, 1H), 7.63 (t, J=7.3 Hz, 1H),
7.41 (d, J=8.2 Hz, 1H), 7.35 (t, J=7.3 Hz, 1H), 7.29 (d, J=
8.3 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 7.04 (d, J=7.8 Hz,
2H), 6.64 (d, J=8.8 Hz, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 2.39
(s, 3H); 13C NMR (100 MHz, CDCl3): d=162.3, 159.3, 150.5,
144.6, 138.8, 133.4, 132.0, 131.2, 129.3, 127.6, 125.3, 124.8,
123.7, 122.5, 117.9, 113.8, 113.1, 55.0, 30.2, 21.5; MS: m/z
(M+ +1)=436, calcd. 436; HR-MS: m/z=435.1143, calcd.
for C24H21NO5S: 435.1140.
1
2
3
4
5
6
C6H5 (3a)
4-MeOC6H4 4a
C6H5 4b
4-CF3C6H4 4c
3-CF3C6H4 4d
84
75
70
73
68
70
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
4-MeOC6H4 (3c) 3-CF3C6H4 4e
3-CF3C6H4 (3f) 3-CF3C6H4 4f
[a]
Isolated yield based on substrate 3.
tronic demands on aromatic rings involving electron-
donating and electron-withdrawing groups, similar re-
sults were obatined when reacted with trifluorometh-
yl-phenylboronic acid (Table 3, entries 5 and 6).
Meanwhile, disubstitution of 3-bromo-4-tosyloxy-
quinolin-2(1H)-one 2 with 3.0 equivs. of arylboronic
acid was tested under the conditions shown in
Table 3. Fortunately, this reaction also performed
smoothly to afford the final product in good yield.
For instance, reaction of 3-bromo-4-tosyloxyquinolin-
2(1H)-one 2 with 4-methoxyphenylboronic acid fur-
nished the desired disubstituted product 5a in 88%
yield (Scheme 3).
Conclusions
In summary, the palladium-catalyzed regioselective
cross-coupling reactions of 3-bromo-4-tosyloxyquino-
lin-2(1H)-one with arylboronic acids disclosed herein
represent a simple, general, efficient, and practical
synthesis of 3,4-disubstituted quinolin-2(1H)-ones.
The advantages of this method include good substrate
generality, mild reaction conditions, and experimental
ease.
1-Methyl-2-oxo-3-p-tolyl-1,2-dihydroquinolin-4-yl 4-meth-
ylbenzenesulfonate (3d): 1H NMR (400 MHz, CDCl3): d=
8.15 (d, J=8.3 Hz, 1H), 7.63 (t, J=7.3 Hz, 1H), 7.41 (d, J=
8.8 Hz, 1H), 7.35 (t, J=7.3 Hz, 1H), 7.26–7.24 (m, 2H), 7.10
(d, J=7.8 Hz, 2H), 7.02 (d, J=8.3 Hz, 2H), 6.93 (d, J=
7.8 Hz, 2H), 3.75 (s, 3H), 2.40 (s, 3H), 2.31 (s, 3H);
Scheme 3.
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A Facile and Convenient Route to 3,4-Disubstituted Quinolin-2(1H)-ones
FULL PAPERS
13C NMR (100 MHz, CDCl3): d=162.2, 150.6, 144.6, 138.9,
137.7, 133.3, 131.3, 120.5, 129.2, 128.6, 128.3, 127.6, 125.4,
125.2, 122.5, 117.8, 113.8, 30.2, 21.6, 21.3; MS: m/z (M+ +
1)=420, calcd.: 420; HR-MS: m/z=419.1195, calcd. for
C24H21NO4S: 419.1191.
1-Methyl-2-oxo-3-(4-(trifluoromethyl)phenyl)-1,2-dihydro-
quinolin-4-yl 4-methylbenzenesulfonate (3e): 1H NMR
(400 MHz, CDCl3): d=8.21 (d, J=8.3 Hz, 1H), 7.69 (t, J=
7.3 Hz, 1H), 7.46–7.24 (m, 9H), 7.03 (d, J=8.3 Hz, 2H),
3.77 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
161.6, 151.4, 145.4, 139.3, 135.5, 133.0, 132.0, 131.2, 129.5,
129.4, 127.4, 125.7, 124.4, 123.6, 122.8, 117.5, 114.0, 30.3,
21.4; MS: m/z (M+ +1)=474, calcd.: 474; HR-MS: m/z=
473.0906, calcd. for C24H18F3NO4S: 473.0909.
1-Methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2-dihydro-
quinolin-4-yl 4-methylbenzenesulfonate (3f): 1H NMR
(400 MHz, CDCl3): d=8.16 (d, J=7.8 Hz, 1H), 7.68 (t, J=
7.3 Hz, 1H), 7.44 (d, J=8.3 Hz, 1H), 7.38 (t, J=7.3 Hz,
1H), 7.30 (d, J=8.3 Hz, 2H), 7.22–7.16 (m, 2H), 7.08–7.03
(m, 4H), 3.77 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=161.6, 151.1, 148.5, 145.4, 139.2, 133.6, 132.9,
131.9, 129.5, 129.3, 128.8, 127.5, 125.8, 123.5, 123.4, 122.7,
121.6, 116.4, 114.0, 30.3, 21.5; MS: m/z (M+ +1)=474,
(127 mg, 0.60 mmol) was stirred in t-BuOH (2 mL) under ni-
trogen at 808C. The reaction mixture was stirred overnight.
Following completion of the reaction as monitored by TLC,
the reaction mixture was diluted with ethyl acetate (20 mL)
and separated. The solution was dried and filtered, and the
filtrate was concentrated to a residue which was purified by
flash chromatography [silica gel, 2/1 (v/v) hexane/ethyl ace-
tate] to give the corresponding product 4 or 5.
4-(4-Methoxyphenyl)-1-methyl-3-phenylquinolin-2(1H)-
1
one (4a): H NMR (400 MHz, CDCl3): d=7.55 (t, J=7.3 Hz,
1H), 7.43 (d, J=8.8 Hz, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.20–
6.09 (m, 6H), 7.01 (d, J=8.7 Hz, 2H), 6.78 (d, J=8.8 Hz,
2H), 3.82 (s, 3H), 3.76 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=161.8, 158.8, 147.4, 139.5, 136.1, 132.1, 131.1,
130.6, 130.1, 128.4, 127.4, 126.7, 121.7, 113.9, 113.3, 55.1,
30.0; MS: m/z (M+ +1)=342, calcd.: 342; HR-MS: m/z=
341.1419, calcd. for C23H19NO2: 341.1416.
1-Methyl-3,4-diphenylquinolin-2(1H)-one (4b): 1H NMR
(400 MHz, CDCl3): d=7.57 (t, J=7.3 Hz, 1H), 7.45 (d, J=
8.3 Hz, 1H), 7.31–7.23 (m, 4H), 7.16–7.08 (m, 8H), 3.85 (s,
3H); 13C NMR (100 MHz, CDCl3): d=161.8, 147.7, 139.4,
136.2, 135.8, 131.9, 130.5, 130.2, 129.8, 128.4, 127.9, 127.4,
126.8, 121.8, 121.4, 114.0, 30.0; MS: m/z (M+ +1)=312,
calcd.: 312; HR-MS: m/z=311.1312, calcd. for C22H17NO:
311.1310.
calcd.:
474;
HR-MS:
m/z=473.0905,
calcd.
for
C24H18F3NO4S: 473.0909.
3-(4-Cyanophenyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-
yl 4-methylbenzenesulfonate (3g): 1H NMR (400 MHz,
CDCl3): d=8.14 (d, J=7.8 Hz, 1H), 7.70 (t, J=7.3 Hz, 1H),
7.45 (d, J=8.3 Hz, 1H), 7.41–7.34 (m, 5H), 7.31 (d, J=
8.2 Hz, 2H), 7.13 (d, J=8.3 Hz, 2H), 3.78 (s, 3H), 2.48 (s,
3H); 13C NMR (100 MHz, CDCl3): d=161.3, 151.6, 145.8,
139.4, 136.8, 133.6, 132.3, 131.7, 131.1, 129.6, 127.5, 125.7,
123.2, 122.9, 118.5, 117.4, 114.1, 111.4, 30.3, 21.6; MS: m/z
(M+ +1)=431, calcd.: 431; HR-MS: m/z=430.0982, calcd.
for C24H18N2O4S: 430.0987.
3-(3-Cyanophenyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-
yl 4-methylbenzenesulfonate (3h): 1H NMR (400 MHz,
CDCl3): d=8.14 (d, J=7.8 Hz, 1H), 7.70 (t, J=7.3 Hz, 1H),
7.61 (d, J=7.8 Hz, 1H), 7.46–7.31 (m, 9H), 7.13 (d, J=
7.8 Hz, 1H), 3.77 (s, 3H), 2.46 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=161.4, 151.4, 145.8, 139.3, 135.4, 134.3, 133.2,
133.0, 132.2, 131.1, 129.8, 128.3, 127.5, 125.8, 122.9, 122.7,
118.2, 117.3, 114.0, 112.0, 29.6, 21.6; MS: m/z (M+ +1)=431,
calcd.: 431; HR-MS: m/z=430.0984, calcd. for C24H18N2O4S:
430.0987.
3-(4-Acetylphenyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-
yl 4-methylbenzenesulfonate (3i): 1H NMR (400 MHz,
CDCl3): d=8.17 (d, J=8.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H),
7.72–7.66 (m, 2H), 7.58 (d, J=7.3 Hz,1H), 7.45 (d, J=
8.8 Hz, 1H), 7.40–7.23 (m, 4H), 7.00 (d, J=8.3 Hz,2H), 3.78
(s, 3H), 2.45 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=197.1, 161.8, 151.2, 145.2, 139.2, 136.5, 135.7,
133.2, 131.9, 131.1, 129.5, 128.0, 127.4, 125.6, 124.0, 122.8,
117.5, 114.0, 30.3, 26.4, 21.5; MS: m/z (M+ +1)=448, calcd.:
448; HR-MS: m/z=447.1138, calcd. for C25H21NO5S:
447.1140.
1-Methyl-3-phenyl-4-(4-(trifluoromethyl)phenyl)quinolin-
2(1H)-one (4c): H NMR (400 MHz, CDCl3): d=7.59 (t, J=
1
8.3 Hz, 1H), 7.53 (d, J=7.8 Hz, 2H), 7.46 (d, J=8.8 Hz,
1H), 7.24 (d, J=7.8 Hz, 2H), 7.19–7.14 (m, 5H), 7.09–7.06
(m, 2H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
161.5, 146.1, 140.2, 139.5, 135.3, 132.3, 130.5, 130.4, 130.3,
127.9, 127.6, 127.2, 125.0, 124.4, 122.5, 122.0, 120.8, 114.2,
30.1; MS: m/z (M+ +1)=380, calcd.: 380; HR-MS: m/z=
379.1180, calcd. for C23H16F3NO: 379.1184.
1-Methyl-3-phenyl-4-(3-(trifluoromethyl)phenyl)quinolin-
2(1H)-one (4d):[22] 1H NMR (400 MHz, CDCl3): d=7.59 (t,
J=7.3 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.30 (t, J=8.3 Hz,
1H), 7.26 (d, J=8.3 Hz, 1H), 7.17–7.05 (m, 8H), 6.99 (s,
1H), 3.85 (s, 3H); MS m/z (M+ +1)=380, calcd. for
[C23H16F3NO]: 380.
3-(3-Methoxyphenyl)-1-methyl-4-(3-(trifluoromethyl)phe-
nyl)quinolin-2(1H)-one (4e):[22] 1H NMR (400 MHz, CDCl3):
d=7.85 (t, J=7.3 Hz, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.32 (t,
J=8.3 Hz, 1H), 7.26–7.11 (m, 3H), 7.06 (d, J=8.8 Hz, 1H),
7.01–6.98 (m, 3H), 6.71 (d, J=8.8 Hz, 1H), 3.84 (s, 3H),
3.73 (s, 3H); 13C NMR (125 MHz, CDCl3): d=162.0, 158.8,
146.1, 139.8, 137.7, 133.5, 132.6, 132.0, 130.7, 128.9, 128.1,
127.8, 127.2, 127.1, 124.6, 124.5, 122.4, 121.2, 114.5, 113.5,
55.4, 30.4; MS m/z (M+ +1)=410, calcd. for [C24H18F3NO2]:
410.
1-Methyl-3,4-bis(3-(trifluoromethyl)phenyl)quinolin-
2(1H)-one (4f):[22] 1H NMR (400 MHz, CDCl3): d=7.62 (t,
J=7.3 Hz, 1H), 7.48 (d, J=8.3 Hz, 1H), 7.34 (t, J=8.3 Hz,
1H), 7.30–6.99 (m, 7H), 6.95 (s, 1H), 6.88 (s, 1H), 3.85 (s,
3H); 13C NMR (125 MHz, CDCl3): d=161.4, 147.2, 140.0,
136.9, 136.4, 134.2, 133.3, 131.4, 131.2, 130.9, 130.5, 130.2,
129.1, 128.3, 127.8, 127.0, 125.0, 124.2, 122.7, 120.9, 114.7,
30.5; MS: m/z (M+ +1)=448, calcd. for [C24H15F6NO]: 448.
3,4-Bis(4-methoxyphenyl)-1-methylquinolin-2(1H)-one
(5a):[22] 1H NMR (400 MHz, CDCl3): d=7.55 (t, J=8.3 Hz,
1H), 7.43 (d, J=8.3 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.12
(t, J=7.3 Hz, 1H), 7.04–7.01 (m, 4H), 6.81 (d, J=8.8 Hz,
General Procedure for Synthesis of 3,4-Disubstituted
Quinolin-2(1H)-one 4 or5
A mixture of 3 (0.20 mmol), Pd (OAc)2 (2.2 mg, 0.01 mmol),
ligand A (2.5 mg, 0.02 mmol), arylboronic acid, and K3PO4
Adv. Synth. Catal. 2007, 349, 1943 – 1948
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1947

Zhiyong Wang et al.
FULL PAPERS
2H), 6.72 (d, J=8.8 Hz, 2H), 3.83 (s, 3H), 3.79 (s, 3H), 3.74
(s, 3H); 13C NMR (125 MHz, CDCl3): d=162.3, 159.0, 158.5,
147.5, 139.7, 137.7, 132.1, 132.0, 131.4, 130.3, 129.0, 128.6,
122.1, 122.0, 114.2, 113.7, 113.3, 55.4, 55.3, 30.3; MS: m/z
(M+ +1)=372, calcd. for [C24H21NO3]: 372.
3,4-Bis(3-cyanophenyl)-1-methylquinolin-2(1H)-one
(5b):[22] 1H NMR (400 MHz, CDCl3): d=7.68–7.61 (m, 2H),
7.52–7.31 (m, 9H), 7.21 (t, J=7.8 Hz, 1H), 7.15 (d, J=
7.8 Hz, 1H), 3.86 (s, 3H); 13C NMR (125 MHz, CDCl3): d=
161.1, 146.4, 140.0, 137.3, 136.8, 135.3, 134.4, 133.2, 132.1,
131.8, 131.4, 129.7, 129.0, 128.2, 122.8, 120.5, 118.6, 118.1,
114.8, 113.1, 112.5, 30.5; MS: m/z (M+ +1)=362, calcd. for
[C24H15N3O]: 362.
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nancial support from National Natural Science Foundation
ofChina (20502004, 20642006) and the Science & Technolo-
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gratefully acknowledged.
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