Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)–H amidation reaction: An efficient route to 4-aryl-2-quinolinones

Article abstract of DOI:10.1016/j.tet.2016.11.075

A Pd(II)-catalyzed cascade Heck/intramolecular C(sp²)–H amidation reaction is described for the synthesis of 4-aryl-2-quinolinone derivatives. Substituted cinnamamide containing 2-(pyridin-2-yl)ethanamine unit reacts with aryl iodide to form in

Full text of DOI:10.1016/j.tet.2016.11.075

Tetrahedron xxx (2016) 1e8
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation
reaction: An efficient route to 4-aryl-2-quinolinones
Chengqian Xiao, Ziyi Wang, Min Lei*, Lihong Hu**
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai, PR China
a r t i c l e i n f o
a b s t r a c t
A Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction is described for the syn-
thesis of 4-aryl-2-quinolinone derivatives. Substituted cinnamamide containing 2-(pyridin-2-yl)ethan-
amine unit reacts with aryl iodide to form intermediate by Heck reaction. Then, the intermediate takes
place intramolecular amidation via C(sp2)eH activated process promoted by orientation group.
© 2016 Elsevier Ltd. All rights reserved.
Article history:
Received 27 September 2016
Received in revised form
28 November 2016
Accepted 29 November 2016
Available online xxx
Keywords:
4-Aryl-2-quinolinone
C(sp2)eH activation
Intramolecular amidation
Directing group
Cascade reaction
1. Introduction
preparing 4-aryl-2-quinolinones from N-methoxycinnamamide
and aryl boronic acid.10
2-Quinolinones are one of the most prevalent heterocyclic
compounds because of their significant biological activities, such as
anticancer,1 antimicrobial,2 antivirus3 and as oxytocin antagonist.4
In recent years, 4-aryl-2-quinolinones have received considerable
attention, for example, the drug candidate Tipifarnib shows excel-
lent results in clinical trials.5 In addition, 4-aryl-2-quinolinone unit
also can be found in natural products.6 Therefore, the synthesis of
4-aryl-2-quinolinone derivatives attracts interesting of organic and
medicinal chemists.
Inspired by the work mentioned above, we envisioned a Pd(II)-
catalyzed Heck/C(sp2)eH activation/intramolecular C(sp2)eH ami-
dation process to synthesis 4-aryl-2-quinolinones. As shown in
Scheme 1(b), cinnamamides containing 2-(pyridin-2-yl)ethana
Scheme 1e unit reacted with aryl iodides to form 3,3-
diarylacrylamides which took place intramolecular amidation re-
action in the presence of Pd(II) via C(sp2)eH activated process. As
orientation group, 2-(pyridin-2-yl)ethanamine unit was introduced
to substrate to promote C(sp2)eH activation.
Over the past decades, various strategies have been developed
to access 4-aryl-2-quinolinones.7 Among these methods, intra-
molecular cyclization played an important role. As shown in
Scheme 1(a), Battistuzzi G. et al. reported a Heck/intramolecular
Buchwald-Hartwig route to synthesis of 4-aryl-2-quinolinones
catalyzed by Pd(0) in 2007.8 Inamoto et al. and Yu et al. found
that 3,3-diarylacrylamides can undergo Pd(II)-catalyzed CeH
functionalization followed by intramolecular amidation to provide
corresponding products.7c,9 Inamoto et al. successfully developed
Pd(II)-catalyzed Heck/intramolecular amidation processes for
In order to validate the feasibility of our ideas, the reaction of N-
(2-(pyridin-2-yl)ethyl)cinnamamide
(1a)
and
1-iodo-4-
methoxybenzene (2a) was carried out in the presence of
Pd(OAc)2 as catalyst, PPh3 as ligand, Cu(OAc)2$H2O as oxidant,
K2CO3 as base in toluene at 120 ꢀC for 11 h. After the reaction was
completed, the mixture was determined by LC-MS. The result
showed that the contents of 1a, 3aa and 3a were 20%, 16% and 37%,
respectively. Despite the yield of the desired product 3a was
dissatisfactory, the result demonstrated that the route to synthesis
of 4-aryl-2-quinolinones was reasonable and feasible. To improve
the yield of 3a, the model reaction was carried out under different
conditions, and the results are summarized in Table 1.
* Corresponding author.
** Corresponding author.
E-mail addresses: mlei@simm.ac.cn (M. Lei), lhhu@simm.ac.cn (L. Hu).
http://dx.doi.org/10.1016/j.tet.2016.11.075
0040-4020/© 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

2
C. Xiao et al. / Tetrahedron xxx (2016) 1e8
Table 1
Optimization of the reaction conditions.a
Entry
Oxidant (equiv.)
Yield (%)b
1a
3aa
3a
1
2
3
4
5
6
7
8
air
12
10
40
38
40
7
33
20
26
8
14
12
11
5
10
19
9
19
0
14
0
36
8
3
62
80
5
1
4
58
32
16
15
84
70
70
62
57
40
47
4
29
0
31
5
34
14
4
3
4
0
0
0
3
0
37
4
O2 (1 atm)
1,4-BQ (3)
PIDA (3)
PIFA(3)
K2S2O8 (3)
m-CPBA (3)
Cu(OAc)2$H2O (3)
Cu(TFA)2$xH2O (3)
CuO (3)
CuSO4 (3)
CuSO4$5H2O (3)
Ag2O (3)
Ag2SO4 (3)
Ag2CO3 (3)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
5
7
11
13
28
21
24
64
24
69
31
69
14
36
49
Scheme 1. The routes to synthesize of 4-aryl-2-quinolinones.
AgOAc (3)
Cu(OAc)2$H2O (3)/Ag2O (3)
Cu(OAc)2$H2O (3)/Ag2SO4 (3)
Cu(OAc)2$H2O (3)/Ag2CO3 (3)
Cu(OAc)2$H2O (3)/AgOAc (3)
Cu(OAc)2$H2O (2)/Ag2CO3 (3)
Cu(OAc)2$H2O (1)/Ag2CO3 (3)
Cu(OAc)2$H2O (3)/Ag2CO3 (2)
Cu(OAc)2$H2O (3)/Ag2CO3 (1)
2. Results and discussion
In our preliminary studies, we found that the oxidants had a
significant impact on the yields of the reaction. Hence, various
oxidants such as air, O2, 1,4-benzoquinone, PIDA, PIFA, K2S2O8, m-
CPBA, Cu(II) salts, and Ag(I) salts were applied to promote the yields
of 3a (Table 1). As shown in Table 1, no or very low yields of 3a were
formed as indicated by LC-MS (Table 1, entries 1e7) except Cu(II)
salts, and Ag(I) salts. The yields of 3a ranged from 13 to 28% in the
presence of Ag(I) salts as oxidants (Table 1, entries 13e16). Among
all of the oxidants screened, Cu(OAc)2$H2O showed the best result
with the yields of 3a in 37% (Table 1, entry 8). These experimental
results revealed that the yields of 3a were not ideal if only using
mono-oxidant (Table 1, entries 1e16). Hence, this model reaction
was carried out in the presence of Cu(OAc)2$H2OeAg(I) salts as
complex oxidants (Table 1, entries 17e20). To our delight, the yield
of 3a was improved significantly (69%) when using
Cu(OAc)2$H2OeAg2CO3 as oxidant (Table 1, entry 19). Further
optimizing the amount of oxidant showed that 2 equiv. of
Cu(OAc)2$H2O and 3 equiv. Ag2CO3 were optimal.
In addition, the other factors, such as base, solvent, catalyst,
ligand and temperature, were also investigated and these contents
were provided in Electronic Supplementary Information (ESI).
Then, the optimal reaction conditions was established: Pd(OAc)2
(30 mol%) as catalyst, PPh3 (60 mol%) as ligand, K2CO3 (3 equiv.) as
base, Cu(OAc)2$H2O (2 equiv.) and Ag2CO3 (3 equiv.) as oxidants,
toluene as solvent at 130 ꢀC. Having established the optimized re-
action conditions, we then carried out the reaction under the
similar conditions using aromatic compounds with different leav-
ing groups, such as Br-, Cl-, TsO-, and TfO-, as substrates to replace
iodobenzene. In these cases, the results showed that the desired 3a
was not formed as indicated by LC-MS (See ESI).
a
Reactions were carried out on a 0.4 mmol scale for 11 h in 3 mL toluene.
Yields were determined by LC-MS.
b
demonstrated that this reaction worked well for those aryl iodides
bearing a variety of functional groups, such as -OCH3, -H, -CH3, and
Cl in 52e74% yields. We also found that low yields of desired
products 3 (0e45%) were obtained when using the aryl iodides
with electro-withdrawing group as the starting materials, such as
-F, -NO2, -CN, -CF3 and -COOMe (Table 2, entries 8e13). Further-
more, ortho, meta and para substituted substrates were chosen to
exam the steric hindrance on this reaction. The desired products 3c
and 3j were obtained in 31% and 0% yields, respectively. These re-
sults clearly indicated that the steric hindrance of aryl iodides could
significant effect on this Heck/intramolecular C(sp2)eH amidation
reaction. The reaction could not proceed smoothly to obtain the
product 3j starting from 1-iodo-2-nitrobenzene (Table 2, entry 10).
In this case, only N-(2-nitrophenyl)-N-(2-(pyridin-2-yl)ethyl)cin-
namamide was formed in 22% yield (Scheme 2).
We next investigated substituted cinnamamides that bearing
-OMe or -Cl at ortho or para (Table 3). para-Substituted substrates
could reacted smoothly to obtain desired products in 55e74% yields
(Table 3, entries 1, 2 and 4). However, only Heck reaction product
was formed if using ortho-Substituted substrate as starting material
(Scheme 3). These results shown steric hindrance of substituents
could affect the reaction greatly.
In order to investigate the selectivity of cyclization, a serials of
meta-substituted N-(2-(pyridin-2-yl)ethyl)cinnamamides were
selected for this reaction (Table 4). Only products 3 were obtained
when meta-substituted cinnamamides (-MeO, -Me, -NO2) were
utilized in the this reaction. Both 3 and 3′ were formed when meta-
To explore the generality and scope of the Heck/intramolecular
C(sp2)eH amidation reaction, the reaction of various aryl iodides
and N-(2-(pyridin-2-yl)ethyl)cinnamamide was carried out under
the optimized conditions (Table 2). The results in Table 2 clearly
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

C. Xiao et al. / Tetrahedron xxx (2016) 1e8
3
Table 2
Table 3
Reaction of aryl iodides with 1a.a
Reaction of N-(2-(pyridin-2-yl)ethyl)cinnamamides with 2a.a
Entry
2 (R1)
Time (h)
Product 3
Yield (%)b
Entry
2 (R2)
Time (h)
Product 3
Yield (%)b
1
2
3
4
5
6
7
8
2a (4-MeO)
2b (3-MeO)
2c (2-MeO)
2d (H)
2e (4-Cl)
2f (3-Cl)
11
11
11
11
46
46
11
40
48
30
24
24
24
3a
3b
3c
3d
3e
3f
3g
3h
3i
74
57
31
62
54
52
70
42
22
0
1
2
3
4
1a (H)
11
11
40
11
3a
3n
3o
3p
74
70
1b (4-MeO)
1c (2-MeO)
1d (4-Cl)
0 (50c)
55
a
Standard conditions: 1 (0.4 mmol), 2a (0.6 mmol, 1.5 equiv.), Pd(OAc)2 (30 mol
%), PPh3 (60 mol%), Cu(OAc)2$H2O (0.8 mmol, 2 equiv.), Ag2CO3 (1.2 mmol, 3 equiv.),
K2CO3 (1.2 mmol, 3 equiv.), toluene (3 mL), 130 ꢀC.
2g (4-Me)
2h (4-F)
b
9
2i (4-NO2)
2j (2-NO2)
2k (4-CN)
2l (4-CF3)
2m (4-COOMe)
Isolated yields.
Heck reaction product was obtained (Scheme 3).
c
10
11
12
13
3j
3k
3l
34
45
42
3m
a
Standard conditions: 1a (0.4 mmol), 2 (0.6 mmol, 1.5 equiv.), Pd(OAc)2 (30 mol
%), PPh3 (60 mol%), Cu(OAc)2$H2O (0.8 mmol, 2 equiv.), Ag2CO3 (1.2 mmol, 3 equiv.),
K2CO3 (1.2 mmol, 3 equiv.), toluene (3 mL), 130 ꢀC.
b
Isolated yields.
Scheme 3. Reaction of 1c and 2a.
Table 4
Reaction of meta-substituted N-(2-(pyridin-2-yl)ethyl)cinnamamides with 2a.a
Scheme 2. Reaction of 1a and 1-iodo-2-nitrobenzene.
substituted cinnamamides carrying -Cl or -F.
Furthermore, this Heck/intramolecular C(sp2)eH amidation re-
action was also applied in natural product vindoline (Scheme 4). At
first, vindoline was iodinated by NIS to form 15-iodo-vindoline.11
Then, the reaction of 15-iodo-vindoline with 1a was carried out
under standard conditions for 11 h to afford product 4 in 20% yield.
On the basis of the experimental results, a possible mechanism
for the formation of 4-aryl-2-quinolinones 3 is presented in
Scheme 5. The initial step, Heck reaction takes place between cin-
namamides 1 and aryl iodides 2. Then, C(sp2)eH is activated via the
intermediate 5, and intermediate 5 undergoes an intramolecular
oxidation cyclization to give the final product 3.
Entry
2 (R3)
Time (h)
Yield (%)b
3
3′
1
2
3
4
5
1e (-MeO)
1f (-Me)
1g (-NO2)
1h (-Cl)
1i (-F)
11
11
11
11
30
3q (80)
3r (67)
3s (67)
3t (45)
3u (20)
3q′ (0)
3r′ (0)
3s′ (0)
3t′ (18)
3u′ (22)
3. Conclusion
a
Standard conditions: 1 (0.4 mmol), 2a (0.6 mmol, 1.5 equiv.), Pd(OAc)2 (30 mol
%), PPh3 (60 mol%), Cu(OAc)2$H2O (0.8 mmol, 2 equiv.), Ag2CO3 (1.2 mmol, 3 equiv.),
K2CO3 (1.2 mmol, 3 equiv.), toluene (3 mL), 130 ꢀC.
In conclusion, we have demonstrated a simple and efficient
method for the synthesis of 4-aryl-2-quinolinones by a Pd(II)-
catalyzed cascade Heck/intramolecular C(sp2)eH amidation reac-
tion. In this process, we introduce 2-(pyridin-2-yl)ethanamine unit
b
Isolated yields.
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

4
C. Xiao et al. / Tetrahedron xxx (2016) 1e8
was refluxed for 1 h. After completion of the reaction, the liquid was
removed under reduced pressure. The residue was dissolved with
anhydrous DCM (10 mL) in flask under N2 protection and cooled in
ice/water bath. Then 2-pyridylethylamine (1.5 mmol) and TEA
(2 mmol) was added dropwise. After the reaction was completed by
monitoring in TLC, water (10 mL) was added to the mixture then the
aqueous phase was extracted with DCM (3 ꢁ 10 mL). The combined
organic layers were washed with brine, dried with anhydrous
Na2SO4, filtered and concentrated. The residue was purified by
chromatograph on silica gel (petroleum ether/acetone ¼ 2/1, v/v) to
give 1.
Scheme 4. The Heck/intramolecular C(sp2)eH amidation reaction applied in natural
products.
4.2.1. N-(2-(Pyridin-2-yl)ethyl)cinnamamide (1a)
Yield: 240 mg (95%); Light yellow solid; mp: 93.8e95.3 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
8.55 (d, J ¼ 4.8 Hz, 1H), 7.62 (dt, J ¼ 7.6,
1.6 Hz, 1H), 7.60 (d, J ¼ 15.6 Hz, 1H), 7.50 (dd, J ¼ 7.6,1.6 Hz, 2H),
7.37e7.32 (m, 3H), 7.19 (d, J ¼ 7.6 Hz, 1H), 7.16 (dd, J ¼ 7.6, 1.6 Hz,
1H), 6.77 (br, 1H), 6.38 (d, J ¼ 15.6 Hz, 1H), 3.80 (dt, J ¼ 12.4, 6.4 Hz,
2H), 3.06 (t, J ¼ 6.4 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 165.82,
159.76, 149.21, 140.62, 136.72, 135.01, 129.54, 128.78 ꢁ 2, 127.78 ꢁ 2,
123.57, 121.65, 121.13, 38.87, 36.87; MS (ESI) m/z 253 [MþH]þ;
HRMS (ESI) calcd for C16H17N2O [MþH]þ 253.1335, found 253.1332.
4.2.2. (E)-3-(4-Methoxyphenyl)-N-(2-(pyridin-2-yl)ethyl)
acrylamide (1b)
Yield: 237 mg (94%); Yellow solid; mp: 58.9e59.8 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.55 (d, J ¼ 4.4 Hz, 1H), 7.62 (dt, J ¼ 7.6, 1.6 Hz,
Scheme 5. The probable mechanism for Heck/intramolecular C(sp2)eH amidation
reaction.
1H), 7.55 (d, J ¼ 15.4 Hz, 1H), 7.44 (d, J ¼ 8.8 Hz, 2H), 7.19 (d,
J ¼ 7.6 Hz, 1H), 7.16 (dd, J ¼ 7.6, 4.4 Hz, 1H), 6.87 (d, J ¼ 8.8 Hz, 2H),
6.65 (br, 1H), 6.25 (d, J ¼ 15.6 Hz, 1H), 3.82 (s, 3H), 3.79 (t, J ¼ 6.0 Hz,
as orientation group of C(sp2)eH activation to promote intra-
molecular oxidation cyclization. This procedure is also applied in
natural product vindoline to obtain corresponding product. The
present study provided a useful supplement for the synthesis of 4-
aryl-2-quinolinones.
2H), 3.05 (t, J ¼ 6.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 166.17,
160.77, 159.76, 149.20, 140.29, 136.75, 129.33 ꢁ 2, 127.66, 123.61,
121.65, 118.64, 114.20 ꢁ 2, 55.38, 38.86, 36.93; MS (ESI) m/z 283
[MþH]þ; HRMS (ESI) calcd for C17H19N2O2 [MþH]þ 283.1441, found
283.1445.
4. Experimental section
4.2.3. (E)-3-(2-Methoxyphenyl)-N-(2-(pyridin-2-yl)ethyl)
acrylamide (1c)
Yield: 268 mg (95%); White solid; mp: 84.8e85.9 ꢀC; 1H NMR
4.1. General information
(400 MHz, CDCl3)
d
8.50 (d, J ¼ 4.8 Hz, 1H), 7.87 (d, J ¼ 16.0 Hz, 1H),
All reactions were performed in flame-dried glassware using
sealed tube. Liquids and solutions were transferred with syringes.
All solvents and chemical reagents were obtained from commercial
sources and used without further purifications. Commercially
available chemicals were obtained from Acros Organics, Strem
Chemicals, Alfa Aesar, Adamas-beta, J&K and TCI. Melting points were
measured by a WRS-1B micromelting point apparatus and are
uncorrected. 1H and 13C NMR spectra were recorded on a Bruker
AMX 400 instrument with tetramethylsilane as an internal refer-
ence at 400 MHz and 101 MHz, respectively. Spectra were refer-
enced to the residual solvent peak of CDCl3 unless otherwise noted.
High-resolution mass spectra (HRMS) were measured on a Micro-
mass Q-Tof Global mass spectrometer and LCMS was run on Waters
LCMS/SQD þ UPLC H-class spectrometer. Flash column chroma-
tography on silica gel (200e300 mesh) was used for the routine
purification of reaction products. The column output was moni-
tored by analytical thin-layer chromatography (TLC) on silica gel
(100e200 mesh) precoated on glass plates (15 ꢁ 50 mm), and spots
were visualized by ultraviolet light at 254 or 365 nm.
7.58 (dt, J ¼ 7.6, 2.0 Hz, 1H), 7.43 (dd, J ¼ 7.0, 1.6 Hz, 1H), 7.27 (dt,
J ¼ 8.0, 1.6 Hz, 1H), 7.17 (d, J ¼ 7.6 Hz, 1H), 7.12 (dd, J ¼ 7.6, 4.8 Hz,
1H), 7.04 (t, J ¼ 5.2 Hz,1H), 6.88 (t, J ¼ 8.0 Hz,1H), 6.85 (d, J ¼ 8.0 Hz,
1H), 6.53 (d, J ¼ 16.0 Hz, 1H), 3.80 (s, 3H), 3.78 (q, J ¼ 6.4 Hz, 2H),
3.05 (t, J ¼ 6.4 Hz, 2H). MS (ESI) m/z 283 [MþH]þ; HRMS (ESI) calcd
for C17H19N2O2 [MþH]þ 283.1441, found 283.1446.
4.2.4. (E)-3-(4-Chlorophenyl)-N-(2-(pyridin-2-yl)ethyl)acrylamide
(1d)
Yield: 276 mg (96%); White solid; mp: 131.5e132.8 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.51 (d, J ¼ 4.4 Hz, 1H), 7.59 (dt, J ¼ 7.6, 1.6 Hz,
1H), 7.52 (d, J ¼ 15.6 Hz, 1H), 7.36 (d, J ¼ 7.6 Hz, 2H), 7.27 (d,
J ¼ 7.6 Hz, 2H), 7.16 (d, J ¼ 7.6 Hz, 1H), 7.13 (dd, J ¼ 7.6, 4.4 Hz, 1H),
7.03 (br, 1H), 6.37 (d, J ¼ 15.6 Hz, 1H), 3.77 (q, J ¼ 6.4 Hz, 2H), 3.03 (t,
J ¼ 6.4 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 165.53, 159.60, 149.10,
139.15, 136.69, 135.25, 133.45, 128.95 ꢁ 2, 128.89 ꢁ 2, 123.51, 121.69,
121.62, 38.90, 36.81; MS (ESI) m/z 287 [MþH]þ; HRMS (ESI) calcd
for C16H16ClN2O [MþH]þ 287.0946, found 287.0944.
4.2.5. (E)-3-(3-Methoxyphenyl)-N-(2-(pyridin-2-yl)ethyl)
acrylamide (1e)
4.2. Experimental procedure for the synthesis of compound 1
Yield: 241 mg (85%); White solid; mp: 96.5e96.7 ꢀC; 1H NMR
To
a
solution of substituted cinnamic acid (1 mmol) in
(400 MHz, CDCl3)
d
8.53 (d, J ¼ 4.8 Hz, 1H), 7.62 (dt, J ¼ 7.6, 1.6 Hz,
dichloromethane (DCM, 2 mL) were added oxalyl chloride (0.5 mL)
and a few drops of DMF at room temperature. Then the reaction
1H), 7.55 (d, J ¼ 16.0 Hz, 1H), 7.25 (t, J ¼ 8.0 Hz, 1H), 7.18 (d,
J ¼ 7.6 Hz, 1H), 7.16 (dd, J ¼ 7.6, 4.4 Hz, 1H), 7.07 (d, J ¼ 8.0 Hz, 1H),
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

C. Xiao et al. / Tetrahedron xxx (2016) 1e8
5
7.00 (d, J ¼ 2.4 Hz, 1H), 6.86 (dd, J ¼ 8.0, 2.4 Hz, 1H), 6.77 (br, 1H),
6.37 (d, J ¼ 16.0 Hz, 1H), 3.80 (s, 3H), 3.79 (q, J ¼ 6.4 Hz, 2H), 3.05 (t,
1.2 mmol) were mixed in a flask and then toluene (3 mL) was added
as solvent. The reaction was refluxted for appropriate time
(Tables 1e4) at 130 ꢀC. Then the mixture was filtrated with celite
and the filtrate was concentrated under reduced pressure. The
residue was purified by chromatograph on silica gel (petroleum
ether/acetone ¼ 10/1 to 7/1, v/v) to give compound 3.
J ¼ 6.4 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 165.76, 159.80, 159.69,
149.17, 140.53, 136.76, 136.34, 129.77, 123.59, 121.67, 121.36, 120.41,
115.26, 112.86, 55.29, 38.88, 36.82; MS (ESI) m/z 283 [MþH]þ;
HRMS (ESI) calcd for
283.1438.
C
17H19N2O2 [MþH]þ 283.1441, found
4.3.1. (E)-3-(4-Methoxyphenyl)-3-phenyl-N-(2-(pyridin-2-yl)ethyl)
acrylamide (3aa)
4.2.6. (E)-N-(2-(Pyridin-2-yl)ethyl)-3-(m-tolyl)acrylamide (1f)
Yield: 256 mg (96%); Light yellow solid; mp: 73.6e76.6 ꢀC; 1H
Yield: 115 mg (80%); Colorless gum; 1H NMR (400 MHz, CDCl3)
NMR (400 MHz, CDCl3)
d
8.56 (d, J ¼ 4.8 Hz, 1H), 7.63 (dt, J ¼ 7.6,
d
8.40 (d, J ¼ 5.2 Hz, 1H), 7.55 (dt, J ¼ 7.6, 1.6 Hz, 1H), 7.28e7.25 (m,
2.0 H, 1H), 7.57 (d, J ¼ 15.6 Hz, 1H), 7.31 (s, 1H), 7.30 (d, J ¼ 7.6 Hz,
1H), 7.25 (t, J ¼ 7.6 Hz, 1H), 7.19 (d, J ¼ 7.6 Hz, 1H), 7.17 (d, J ¼ 7.6 Hz,
1H), 7.16 (dd, J ¼ 7.6, 4.8 Hz, 1H), 6.71 (br, 1H), 6.36 (d, J ¼ 15.6 Hz,
1H), 3.81 (q, J ¼ 6.0 Hz, 2H), 3.06 (t, J ¼ 6.0 Hz, 2H); 13C NMR
3H), 7.19 (dd, J ¼ 7.6, 2.0 Hz, 2H), 7.17 (d, J ¼ 8.4 Hz, 2H), 7.10 (dd,
J ¼ 7.6, 5.2 Hz, 1H), 7.01 (dd, J ¼ 7.6 Hz, 1H), 6.82 (d, J ¼ 8.4 Hz, 2H),
6.31 (s, 1H), 5.95 (t, J ¼ 8.0 Hz, 1H), 3.80 (s, 3H), 3.52 (q, J ¼ 8.0 Hz,
2H), 2.73 (t, J ¼ 8.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 166.85,
(101 MHz, CDCl3)
d
165.96, 159.66, 149.15, 140.72, 138.35, 136.70,
160.33,159.40, 149.25, 149.07, 138.82, 136.48, 133.42, 129.43, 129.41,
128.51,128.44,123.38,121.45,121.13,113.83, 55.45, 38.38, 36.88; MS
(ESI) m/z 359 [MþH]þ; HRMS (ESI) calcd for C23H23N2O2 [MþH]þ
359.1754, found 359.1757.
134.86, 130.35, 128.63, 128.43, 124.93, 123.56, 121.63, 120.83, 38.89,
36.91, 21.35; MS (ESI) m/z 267 [MþH]þ; HRMS (ESI) calcd for
C
17H19N2O [MþH]þ 267.1492, found 267.1489.
4.2.7. (E)-3-(3-Nitrophenyl)-N-(2-(pyridin-2-yl)ethyl)acrylamide
(1g)
4.3.2. 4-(4-Methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-
2(1H)-one (3a)
Yield: 223 mg (75%); Yellow solid; mp: 150.7e152.0 ꢀC; 1H NMR
Yield: 106 mg (74%); Light yellow solid; mp: 207.2e207.7 ꢀC; 1H
(400 MHz, CDCl3)
d
8.57 (d, J ¼ 4.4 Hz, 1H), 8.37 (s, 1H), 8.17 (d,
NMR (400 MHz, CDCl3)
d
8.62(d, J ¼ 4.8 Hz, 1H), 7.69 (d, J ¼ 8.0 Hz,
J ¼ 8.0 Hz, 1H), 7.77 (d, J ¼ 8.0 Hz, 1H), 7.65 (d, J ¼ 15.6 Hz, 1H), 7.64
(dt, J ¼ 7.6, 2.0 Hz, 1H), 7.54 (t, J ¼ 8.0 Hz, 1H), 7.19 (d, J ¼ 7.6 Hz, 1H),
7.18 (dd, J ¼ 7.6, 4.4 Hz, 1H), 7.06 (br, 1H), 6.53 (d, J ¼ 15.6 Hz, 1H),
3.83 (q, J ¼ 6.0 Hz, 2H), 3.06 (t, J ¼ 6.0 Hz, 2H); MS (ESI) m/z 298
[MþH]þ; HRMS (ESI) calcd for C16H16N3O2 [MþH]þ 298.1186, found
298.1181.
1H), 7.63 (t, J ¼ 7.6 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 7.58 (t, J ¼ 8.0 Hz,
1H), 7.37 (d, J ¼ 8.4 Hz, 2H), 7.30 (d, J ¼ 7.6 Hz, 1H), 7.18 (dd, J ¼ 7.6,
4.8 Hz, 1H), 7.16 (t, J ¼ 8.0 Hz, 1H), 7.02 (d, J ¼ 8.4 Hz, 1H), 6.67 (s,
1H), 4.73 (m, 2H), 3.89 (s, 3H), 3.26 (m, 2H); 13C NMR (101 MHz,
CDCl3) d 161.92, 160.11, 158.74, 151.01, 149.63, 139.59, 136.79, 130.90,
130.38 ꢁ 2, 129.58, 128.01, 123.87, 121.93, 121.91, 121.09, 120.99,
114.83, 114.15 ꢁ 2, 55.53, 42.59, 35.99; MS (ESI) m/z 357 [MþH]þ;
HRMS (ESI) calcd for C23H21N2O2 [MþH]þ 357.1598, found 357.1595.
4.2.8. (E)-3-(3-Chlorophenyl)-N-(2-(pyridin-2-yl)ethyl)acrylamide
(1h)
Yield: 238 mg (83%); Light yellow solid; mp: 69.6e71.2 ꢀC; 1H
4.3.3. 4-(3-Methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-
2(1H)-one (3b)
NMR (400 MHz, CDCl3)
d
8.55 (d, J ¼ 4.8 Hz, 1H), 7.62 (dt, J ¼ 7.6,
1.6 Hz, 1H), 7.53 (d, J ¼ 15.6 Hz, 1H), 7.47 (s, 1H), 7.34 (dd, J ¼ 8.0,
1.6 Hz, 1H), 7.28 (t, J ¼ 8.0 Hz, 1H), 7.27 (d, J ¼ 8.0 Hz, 1H), 7.18 (d,
J ¼ 7.6 Hz, 1H), 7.17 (dd, J ¼ 7.6, 4.8 Hz, 1H), 6.94 (br, 1H), 6.38 (d,
Yield: 81 mg (57%); Light yellow gum; 1H NMR (400 MHz, CDCl3)
d
8.63 (d, J ¼ 4.0 Hz, 1H), 7.70 (d, J ¼ 8.0 Hz, 1H), 7.64 (dt, J ¼ 7.6,
1.6 Hz, 1H), 7.59 (d, J ¼ 7.6 Hz, 1H), 7.58 (dt, J ¼ 8.0, 1.2 Hz, 1H), 7.41
(t, J ¼ 8.0 Hz,1H), 7.31 (d, J ¼ 8.0 Hz,1H), 7.19 (dd, J ¼ 7.6, 4.0 Hz,1H),
7.16 (dt, J ¼ 8.0,1.2 Hz,1H), 7.02 (d, J ¼ 8.0 Hz,1H), 7.01 (d, J ¼ 8.0 Hz,
1H), 6.96 (t, J ¼ 2.0 Hz, 1H), 6.70 (s, 1H), 4.7e4.71 (m, 2H), 3.85 (s,
J ¼ 15.6 Hz, 1H), 3.80 (q, J ¼ 6.4 Hz, 2H), 3.05 (t, J ¼ 6.4 Hz, 2H); 13
C
NMR (101 MHz, CDCl3)
d 165.29, 159.68, 149.18, 139.17, 136.82,
136.80, 134.74, 130.04, 129.43, 127.33, 126.21, 123.60, 122.45, 121.72,
38.88, 36.68; MS (ESI) m/z 287 [MþH]þ; HRMS (ESI) calcd for
3H), 3.26 (m, 2H); 13C NMR (101 MHz, CDCl3)
d 161.82, 159.72,
C
16H16ClN2O [MþH]þ 287.0946, found 287.0947.
158.67, 151.18, 149.59, 139.51, 138.60, 136.82, 131.01, 129.76, 128.01,
123.87, 122.02, 121.93, 121.43, 121.16, 120.73, 114.81, 114.61, 114.35,
55.50, 42.63, 35.95; MS (ESI) m/z 357 [MþH]þ; HRMS (ESI) calcd for
4.2.9. (E)-3-(3-Fluorophenyl)-N-(2-(pyridin-2-yl)ethyl)acrylamide
(1i)
C
23H21N2O2 [MþH]þ 357.1598, found 357.1594.
Yield: 255 mg (94%); White solid; mp: 88.8e89.9 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.54 (d, J ¼ 4.4 Hz, 1H), 7.62 (dt, J ¼ 7.6, 1.6 Hz,
4.3.4. 4-(2-Methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-
2(1H)-one (3c)
1H), 7.55 (d, J ¼ 15.6 Hz, 1H), 7.30 (dq, J ¼ 7.6, 1.6 Hz, 1H), 7.24 (d,
J ¼ 7.6 Hz,1H), 7.18 (d, J ¼ 7.6 Hz,1H), 7.17 (d, J ¼ 7.6 Hz,1H), 7.16 (dd,
J ¼ 7.6, 4.4 Hz, 1H), 7.02 (dt, J ¼ 7.6, 1.2 Hz, 1H), 6.95 (br, 1H), 6.38 (d,
Yield: 44 mg (31%); White solid; mp: 147.4e148.2 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.63 (d, J ¼ 4.0 Hz, 1H), 7.69 (d, J ¼ 8.0 Hz, 1H),
J ¼ 15.6 Hz, 1H), 3.79 (q, J ¼ 6.0 Hz, 2H), 3.05 (t, J ¼ 6.0 Hz, 2H); 13
C
7.64 (dt, J ¼ 7.6, 1.2 Hz, 1H), 7.56 (dt, J ¼ 8.0, 1.6 Hz, 1H), 7.46 (dt,
J ¼ 8.0, 1.6 Hz, 1H), 7.33 (d, J ¼ 7.6 Hz, 1H), 7.28 (dd, J ¼ 8.0, 1.2 Hz,
1H), 7.23 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.19 (dd, J ¼ 6.8, 6.0 Hz, 1H), 7.11 (t,
J ¼ 8.0 Hz, 1H), 7.08 (t, J ¼ 8.0 Hz,1H), 7.04 (d, J ¼ 8.0 Hz,1H), 6.68 (s,
1H), 4.79e4.66 (m, 2H), 3.74 (s, 3H), 3.27 (t, J ¼ 8.0 Hz); 13C NMR
NMR (101 MHz, CDCl3)
d
165.37,164.20 and 161.76 (1JC-F ¼ 247.1 Hz),
159.67, 149.17, 139.36 and 139.33 (4JC-F¼2.3 Hz), 137.30 and 137.22
(3JC-F ¼ 7.8 Hz), 136.77, 130.34 and 130.26 (3JC-F ¼ 8.4 Hz), 123.88
and 123.86 (4JC-F ¼ 2.5 Hz), 123.58, 122.42, 121.69, 116.48 and 116.27
(2JC-F ¼ 21.3 Hz), 114.02 and 113.80 (2JC-F ¼ 21.7 Hz), 38.89, 36.73;
MS (ESI) m/z 271 [MþH]þ; HRMS (ESI) calcd for C16H16FN2O
[MþH]þ 271.1241, found 271.1243.
(101 MHz, CDCl3)
d 162.05, 158.84, 156.73, 149.62, 148.92, 139.13,
136.78, 130.73, 130.68, 130.31, 128.12, 126.22, 123.90, 122.10, 121.89,
121.81,121.13,120.93, 114.60,111.18, 55.69, 42.66, 36.03; MS (ESI) m/
z 357 [MþH]þ; HRMS (ESI) calcd for C23H21N2O2 [MþH]þ 357.1598,
found 357.1597.
4.3. Experimental procedure for the synthesis of compounds 3
Compound 1 (0.4 mmol), 2 (0.6 mmol), Pd(OAc)2 (27 mg,
0.12 mmol), PPh3 (62 mg, 0.24 mmol), Cu(OAc)2$H2O (160 mg,
0.8 mmol), Ag2CO3 (331 mg, 1.2 mmol) and K2CO3 (166 mg,
4.3.5. 4-Phenyl-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-one (3d)
Yield: 81 mg (62%); Light yellow solid; mp: 142.1e142.4 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.8 Hz, 1H), 7.70 (d, J ¼ 8.4 Hz,
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

6
C. Xiao et al. / Tetrahedron xxx (2016) 1e8
1H), 7.63 (t, J ¼ 7.6 Hz, 1H), 7.58 (t, J ¼ 8.4 Hz, 1H), 7.55 (d, J ¼ 8.4 Hz,
1H), 7.51e7.47 (m, 3H), 7.44e7.42 (m, 2H), 7.30 (d, J ¼ 7.6 Hz, 1H),
7.18 (dd, J ¼ 7.6, 4.8 Hz, 1H), 7.15 (t, J ¼ 8.4 Hz, 1H), 6.69 (s, 1H), 4.74
(400 MHz, CDCl3)
d
8.63 (d, J ¼ 4.4 Hz, 1H), 8.38 (d, J ¼ 8.8 Hz, 2H),
7.75 (d, J ¼ 8.0 Hz, 1H), 7.66e7.62 (m, 4H), 7.39 (d, J ¼ 8.0 Hz, 1H),
7.31 (d,J ¼ 7.6 Hz, 1H), 7.21e7.17 (m, 2H), 6.70 (s, 1H), 4.75 (t,
J ¼ 8.0 Hz, 2H), 3.26 (t, J ¼ 8.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
(m, 2H), 3.26 (m, 2H); 13C NMR (101 MHz, CDCl3)
d 161.77, 158.65,
151.27, 149.59, 139.51, 137.25, 136.75, 130.95, 129.00 ꢁ 2, 128.76,
128.66 ꢁ 2, 127.95, 123.81, 121.96, 121.88, 121.26, 120.74, 114.79,
42.59, 35.93; MS (ESI) m/z 327 [MþH]þ; HRMS (ESI) calcd for
d 161.28, 158.47, 149.69, 148.97, 148.20, 143.85, 139.65, 136.86,
131.58, 130.12, 127.29, 124.07, 123.85, 122.42, 122.02, 121.81, 119.85,
115.20, 42.79, 35.89; MS (ESI) m/z 372 [MþH]þ; HRMS (ESI) calcd
for C22H18N3O3 [MþH]þ 372.1343, found 372.1338.
C
22H19N2O [MþH]þ 327.1492, found 327.1494.
4.3.6. 4-(4-Chlorophenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-
one (3e)
4.3.11. 4-(4-Cyanophenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-
2(1H)-one (3j)
Yield: 78 mg (54%); White solid; mp: 134.7e134.9 ꢀC; 1H NMR
Yield: 47 mg (34%); White solid; mp: 195.2e196.5 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.62 (d,J ¼ 4.4 Hz, 1H), 7.71 (d, J ¼ 8.4 Hz, 1H),
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.8 Hz, 1H), 7.81 (d, J ¼ 8.0 Hz, 2H),
7.63 (dt, J ¼ 7.6, 1.2 Hz, 1H), 7.59 (t, J ¼ 7.6 Hz, 1H), 7.49 (t, J ¼ 7.6 Hz,
1H), 7.47 (d, J ¼ 8.0 Hz, 2H), 7.36 (d, J ¼ 8.0 Hz, 2H), 7.30 (d,
J ¼ 7.6 Hz, 1H), 7.18 (dd, J ¼ 7.6, 4.4 Hz, 1H), 7.17 (d, J ¼ 7.6 Hz, 1H),
6.66 (s, 1H), 4.72 (t, J ¼ 8.0 Hz, 2H), 3.25 (t, J ¼ 8.0 Hz, 2H); 13C NMR
7.74 (d, J ¼ 8.0 Hz, 1H), 7.66e7.60 (m, 2H), 7.56 (d, J ¼ 8.0 Hz, 2H),
7.39 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.30 (d, J ¼ 8.0 Hz, 1H), 7.21e7.16 (m,
2H), 6.67 (s, 1H), 4.76e4.72 (m, 2H), 3.28e3.24 (m, 2H); 13C NMR
(101 MHz, CDCl3)
d 161.34, 158.54, 149.71, 149.29, 142.01, 139.69,
(101 MHz, CDCl3)
d 161.61, 158.58, 150.07, 149.62, 139.56, 136.80,
136.82, 132.61 ꢁ 2, 131.50, 129.87 ꢁ 2,127.32, 123.83, 122.34, 121.99,
121.76, 119.89, 118.50, 115.17, 112.93, 42.76, 35.93; MS (ESI) m/z 352
[MþH]þ; HRMS (ESI) calcd for C23H18N3O [MþH]þ 372.1444, found
372.1451.
135.66, 134.97, 131.17, 130.37, 129.00, 127.65, 123.84, 122.12, 121.94,
121.41, 120.45, 114.95, 42.64, 35.91; MS (ESI) m/z 361 [MþH]þ;
HRMS (ESI) calcd for
361.1106.
C
22H18ClN2O [MþH]þ 361.1102, found
4.3.7. 4-(3-Chlorophenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-
one (3f)
4.3.12. -(4-Trifluoromethylphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3k)
Yield: 75 mg (52%); Light solid; mp: 151.0e151.2 ꢀC; 1H NMR
Yield: 71 mg (45%); White solid; mp: 174.9e175.7 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.4 Hz, 1H), 7.71 (d, J ¼ 8.0 Hz, 1H),
(400 MHz, CDCl3)
d
8.63 (d, J ¼ 5.6 Hz, 1H), 7.77 (d, J ¼ 8.0 Hz, 2H),
7.63 (dt, J ¼ 7.6, 1.6 Hz, 1H), 7.60 (dt, J ¼ 8.0, 1.2 Hz, 1H), 7.50 (dd,
J ¼ 8.0, 1.2 Hz, 1H), 7.45 (s, 1H), 7.46e7.42 (m, 2H), 7.32e7.30 (m,
2H), 7.21e7.16 (m, 2H), 6.67 (s, 1H), 4.73 (m, J ¼ 8.0 Hz, 2H), 3.26 (m,
7.73 (d, J ¼ 8.0 Hz, 1H), 7.66e7.57 (m, 2H), 7.56 (d, J ¼ 8.0 Hz, 2H),
7.44 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.31 (d, J ¼ 8.0 Hz, 1H), 7.21e7.16 (m,
2H), 6.69 (s, 1H), 4.77e4.72 (m, 2H), 3.29e3.25 (m, 2H); 13C NMR
(101 MHz, CDCl3) d 161.48, 158.61, 149.82, 149.69, 140.95, 139.64,
136.79, 131.33,131.52 and 131.20 and 130.87 and 130.55 (q, JC-
J ¼ 8.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d
161.58, 158.59, 149.81,
2
149.62, 139.55, 139.01, 136.84, 134.67, 131.23, 130.08, 129.08, 128.98,
127.67, 127.24, 123.87, 122.20, 121.97, 121.51, 120.37, 114.95, 42.68,
35.92; MS (ESI) m/z 361 [MþH]þ; HRMS (ESI) calcd for C22H18ClN2O
[MþH]þ 361.1102, found 361.1104.
¼ 32.6 Hz), 129.47 ꢁ 2, 127.56, 125.82 and 125.79 and 125.75 and
F
125.71 (q, 3JC-F ¼ 3.5 Hz), 128.16 and 125.45 and 122.75 and 120.04
1
(q, JC-F ¼ 270 Hz), 123.83, 122.23, 121.96, 121.69, 120.26, 115.04,
42.71, 35.95; MS (ESI) m/z 395 [MþH]þ; HRMS (ESI) calcd for
4.3.8. 1-(2-(Pyridin-2-yl)ethyl)-4-(p-tolyl)quinolin-2(1H)-one (3g)
Yield: 95 mg (70%); Light yellow solid; mp: 139.2e140.0 ꢀC; 1H
C
23H18F3N2O [MþH]þ 395.1366, found 372.1347.
NMR (400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.4 Hz, 1H), 7.69 (d, J ¼ 8.4 Hz,
4.3.13. 4-(4-Methyloxycarbonylphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3l)
1H), 7.63 (dt, J ¼ 7.6, 1.2 Hz, 1H), 7.60 (d, J ¼ 8.4 Hz, 1H), 7.58 (t,
J ¼ 8.4 Hz, 1H), 7.34e7.30 (m, 5H), 7.18 (dd, J ¼ 7.6, 5.6 Hz, 1H), 7.15
(t, J ¼ 7.6 Hz, 1H), 6.68 (s, 1H), 4.73 (t, J ¼ 8.0 Hz, 2H), 3.26 (t,
Yield: 65 mg (42%); White solid; mp: 100.0e102.1 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.8 Hz, 1H), 8.17 (d, J ¼ 8.4 Hz, 2H),
J ¼ 8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 161.88,
7.71 (d, J ¼ 8.0 Hz, 1H), 7.63 (dt, J ¼ 8.0, 2.0 Hz, 1H), 7.62e7.58 (m,
1H), 7.51 (d, J ¼ 8.4 Hz, 2H), 7.47 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.30 (d,
J ¼ 8.0 Hz, 1H), 7.20e7.14 (m 2H), 6.69 (s, 1H), 4.76e4.72 (m, 2H),
158.74, 151.34, 149.64, 139.56, 138.75, 136.77, 134.39, 130.90,
129.38 ꢁ 2, 128.98 ꢁ 2, 128.03, 123.85, 121.91, 121.90, 121.17, 120.90,
114.80, 42.59, 36.00, 21.46; MS (ESI) m/z 341 [MþH]þ; HRMS (ESI)
calcd for C23H21N2O [MþH]þ 341.1648, found 341.1645.
3.97 (s, 3H), 3.28e3.24 (m, 2H); 13C NMR (101 MHz, CDCl3)
d 166.74,
161.53, 158.61, 150.24, 149.66, 141.86, 139.60, 136.78, 131.23, 130.55,
129.98 ꢁ 2, 129.15 ꢁ 2, 127.64, 123.83, 122.16, 121.93, 121.48, 120.27,
114.98, 52.48, 42.67, 35.94; MS (ESI) m/z 385 [MþH]þ; HRMS (ESI)
calcd for C24H21N2O3 [MþH]þ 385.1547, found 385.1557.
4.3.9. 4-(4-Fluorophenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-
one (3h)
Yield: 58 mg (42%); White solid; mp: 178.7e178.9 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.8 Hz, 1H), 7.71 (d, J ¼ 8.4 Hz, 1H),
7.63 (dt, J ¼ 7.6, 1.6 Hz, 1H), 7.60 (dt, J ¼ 8.0, 1.2 Hz, 1H), 7.52 (dd,
J ¼ 8.0, 1.2 Hz, 1H), 7.41 (dd, J ¼ 8.8, 6.4 Hz, 2H), 7.30 (d, J ¼ 8.0 Hz,
1H), 7.22e7.16 (m, 4H), 6.67 (s, 1H), 4.73 (t, J ¼ 8.0 Hz, 2H), 3.26 (t,
4.3.14. 7-Methoxy-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3n)
Yield: 108 mg (70%); White solid; mp: 197.7e198.4 ꢀC; 1H NMR
J ¼ 8.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d
161.70 and 158.66 (1JC-
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.8 Hz, 1H), 7.63 (d, J ¼ 9.6 Hz, 1H),
¼ 304 Hz), 150.27, 149.66, 139.59, 136.80, 133.27 and 133.24 (4JC-
¼ 3.0 Hz), 131.12 and 130.87 (2JC-F ¼ 25.0 Hz), 130.79, 127.76,
7.63 (dt, J ¼ 7.6,1.6 Hz,1H), 7.38 (d, J ¼ 8.8 Hz, 2H), 7.30 (d, J ¼ 8.0 Hz,
1H), 7.20 (dd, J ¼ 8.0, 2.8 Hz, 1H), 7.18 (7.6, 5.2 Hz, 1H), 7.08 (d,
J ¼ 2.8 Hz,1H), 7.03 (d, J ¼ 8.8 Hz, 2H), 6.67 (s,1H), 4.70 (t, J ¼ 8.0 Hz,
2H), 3.89 (s, 3H), 3.74 (s, 3H), 3.24 (t, J ¼ 8.0 Hz, 2H); 13C NMR
F
F
123.85, 122.10 and 121.94 (3JC-F ¼ 15.0 Hz), 121.52, 120.72, 115.94,
115.73, 114.93, 42.66, 35.97; MS (ESI) m/z 345 [MþH]þ; HRMS (ESI)
calcd for C22H18FN2O [MþH]þ 345.1398, found 345.1401.
(101 MHz, CDCl3)
d 161.50, 160.09, 158.74, 154.51, 150.39, 149.62,
136.81, 134.11, 130.25 ꢁ 2, 129.64, 123.89, 121.92, 121.82, 121.70,
118.99,116.13,114.21 ꢁ 2,110.44, 55.76, 55.53, 42.74, 36.10; MS (ESI)
m/z 387 [MþH]þ; HRMS (ESI) calcd for C22H23N2O3 [MþH]þ
387.1703, found 387.1699.
4.3.10. 4-(4-Nitrophenyl)-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-
one (3i)
Yield: 33 mg (22%); White solid; mp: 223.0e224.1 ꢀC; 1H NMR
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

C. Xiao et al. / Tetrahedron xxx (2016) 1e8
7
4.3.15. 7-Chloro-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3p)
391 [MþH]þ; HRMS (ESI) calcd for C23H20ClN2O2 [MþH]þ 391.1208,
found 391.1205.
Yield: 86 mg (55%); Light yellow solid; mp: 138.1e140.0 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
8.63 (d, J ¼ 4.4 Hz, 1H), 7.63 (s, 1H), 7.60 (t,
4.3.20. 8-Chloro-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3t0)
J ¼ 7.6 Hz,1H), 7.52 (d, J ¼ 8.4 Hz,1H), 7.34 (d, J ¼ 8.0 Hz, 2H), 7.24 (d,
J ¼ 7.6 Hz, 1H), 7.18 (T J ¼ 7.6 Hz, 1H), 7.09 (d, J ¼ 8.4 Hz, 1H), 7.02 (d,
J ¼ 8.0 Hz, 2H), 6.64 (s, 1H), 4.70 (t, J ¼ 8.0 Hz, 2H), 3.89 (s, 3H), 3.26
Yield: 28 mg (18%); Yellow solid; mp: 155.4e155.6 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.55 (d, J ¼ 4.8 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H),
(t, J ¼ 8.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d
161.83, 160.27,
7.61 (dt, J ¼ 7.6, 1.2 Hz, 1H), 7.49 (dd, J ¼ 8.0, 0.8 Hz, 1H), 7.32 (d,
J ¼ 8.8 Hz, 2H), 7.26 (d, J ¼ 8.0 Hz, 1H), 7.14 (dd, J ¼ 7.6, 5.6 Hz, 1H),
7.06 (t, J ¼ 8.0 Hz, 1H), 7.03 (d, J ¼ 8.8 Hz, 2H), 6.64 (s, 1H), 5.07 (t,
J ¼ 7.6 Hz, 2H), 3.91 (s, 3H), 3.49 (t, J ¼ 7.6 Hz, 2H); 13C NMR
158.49, 150.54, 149.71, 140.55, 137.05, 136.74, 130.29 ꢁ 2, 129.12,
129.11, 123.79, 122.31, 121.99, 121.02, 119.44, 114.84, 114.27 ꢁ 2,
55.55, 42.71, 35.95; MS (ESI) m/z 391 [MþH]þ; HRMS (ESI) calcd for
C
23H20ClN2O2 [MþH]þ 391.1208, found 391.1206.
(101 MHz, CDCl3) d 163.80, 160.18, 159.16, 150.71, 149.45, 138.20,
136.40, 134.40, 130.29 ꢁ 2, 129.41, 127.41, 124.75, 123.50, 122.65,
122.00, 121.55, 120.76, 114.21 ꢁ 2, 55.54, 46.80, 37.89; MS (ESI) m/z
391 [MþH]þ; HRMS (ESI) calcd for C23H20ClN2O2 [MþH]þ 391.1208,
found 391.1203.
4.3.16. 6-Methoxy-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3q)
Yield: 124 mg (80%); White solid; mp: 167.0e167.3 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.60 (d, J ¼ 4.4 Hz, 1H), 7.60 (dt, J ¼ 7.6, 2.0 Hz,
1H), 7.51 (d, J ¼ 8.8 Hz,1H), 7.36 (d, J ¼ 8.8 Hz, 2H), 7.27 (d, J ¼ 7.6 Hz,
1H), 7.27 (d, J ¼ 2.4 Hz, 1H), 7.17 (dd, J ¼ 7.6, 4.4 H, 1H), 7.01 (d,
J ¼ 8.8 Hz, 2H), 6.75 (dd, J ¼ 8.8, 2.4 Hz, 1H), 6.52 (s, 1H), 4.72 (t,
4.3.21. 6-Fluoro-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3u)
Yield: 30 mg (20%); White solid; mp: 170.1e172.9 ꢀC; 1H NMR
J ¼ 7.6 Hz, 2H), 3.95 (s, 3H), 3.88 (s, 3H), 3.26 (t, J ¼ 7.6 Hz, 2H); 13
C
(400 MHz, CDCl3)
d
8.62 (dd, J ¼ 4.8, 0.8 Hz, 1H), 7.68 (dt, J ¼ 7.6,
NMR (101 MHz, CDCl3)
d
162.43, 161.98, 160.03, 158.94, 150.95,
0.8 Hz, 1H), 7.66 (d, J ¼ 7.6 Hz, 1H), 7.63 (dt, J ¼ 7.6, 2.0 Hz, 1H), 7.46
(dt, J ¼ 7.6, 2.8 Hz, 1H), 7.36 (d, J ¼ 8.8 Hz, 2H), 7.31 (dd, J ¼ 7.6,
2.0 Hz, 1H), 7.29 (d, J ¼ 7.6 Hz, 1H), 7.28 (d, J ¼ 7.6 Hz, 1H), 7.18 (ddd,
J ¼ 7.6, 4.8, 0.8 Hz, 1H), 7.04 (d, J ¼ 8.8 Hz, 1H), 6.71 (s, 1H), 4.71 (t,
J ¼ 8.0 Hz, 2H), 3.89 (s, 3H), 3.24 (t, J ¼ 8.0 Hz, 2H); 13C NMR
149.69, 141.36, 136.71, 130.30 ꢁ 2, 129.92, 129.30, 123.78, 121.85,
118.02, 114.96, 114.09 ꢁ 2, 110.11, 98.96, 55.89, 55.51, 42.73, 35.78;
MS (ESI) m/z 387 [MþH]þ; HRMS (ESI) calcd for C22H23N2O3
[MþH]þ 387.1703, found 387.1671.
(151 MHz, CDCl3)
d
161.56, 160.31, 158.59 and 158.56 (1JC-
4.3.17. 4-(4-Methoxyphenyl)-6-methyl-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3r)
¼ 241 Hz), 156.99, 150.15 and 150.13 (4JC-F ¼ 3 Hz), 149.68, 136.83,
F
132.27 and 132.21 (3JC-F ¼ 10 Hz), 130.24 ꢁ 2, 129.02, 128.68 and
Yield: 99 mg (67%); Light yellow solid; mp: 177.2e178.6 ꢀC; 1H
128.60 (3JC-F ¼ 12 Hz), 123.88, 122.22, 121.99, 118.68 and 118.52 (2JC-
NMR (400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.0 Hz, 1H), 7.62 (dt, J ¼ 7.6,
¼ 24 Hz), 116.52 and 116.47 (4JC-F ¼ 7 Hz), 114.36 ꢁ 2, 113.25 and
F
1.6 Hz, 1H), 7.58 (d, J ¼ 1.6 Hz, 1H), 7.37 (d, J ¼ 8.8 Hz, 2H), 7.38 (m,
2H), 7.30 (d, J ¼ 7.6 Hz, 1H), 7.18 (dd, J ¼ 6.4, 5.2 Hz, 1H), 7.03 (d,
J ¼ 8.8 Hz, 2H), 6.64 (s, 1H), 4.70 (t, J ¼ 8.0 Hz, 2H), 3.90 (s, 3H), 3.25
113.09 (2JC-F ¼ 24 Hz), 55.56, 42.90, 36.00; MS (ESI) m/z 375
[MþH]þ; HRMS (ESI) calcd for C23H20FN2O2 [MþH]þ 375.1503,
found 375.1508.
(t, J ¼ 8.0 Hz, 2H), 2.33 (3,3H); 13C NMR (101 MHz, CDCl3)
d 161.66,
159.95, 158.75, 150.63, 149.51, 137.51, 136.62, 131.97, 131.32,
130.23 ꢁ 2, 129.68, 127.56, 123.72, 121.74, 121.08, 120.82, 114.64,
114.04 ꢁ 2, 55.40, 42.46, 35.95, 20.78; MS (ESI) m/z 371 [MþH]þ;
HRMS (ESI) calcd for C24H23N2O2 [MþH]þ 371.1754, found 371.1753.
4.3.22. 8-Fluoro-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3u0)
Yield: 33 mg (22%); White solid; mp: 162.8e164.2 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
8.58 (d, J ¼ 3.6 Hz, 1H), 7.63 (t, J ¼ 7.6 Hz, 1H),
7.39 (d, J ¼ 8.0 Hz,1H), 7.33 (d, J ¼ 8.0 Hz, 3H), 7.29 (d, J ¼ 7.6 Hz,1H),
7.16 (t, J ¼ 6.0 Hz,1H), 7.08 (dt, J ¼ 8.0, 4.4 Hz,1H), 7.02 (d, J ¼ 8.0 Hz,
2H), 6.66 (s, 1H), 4.84 (br, 2H), 3.88 (s, 3H), 3.34 (t, J ¼ 8.0 Hz, 2H);
4.3.18. 4-(4-Methoxyphenyl)-6-nitro-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3s)
Yield: 107 mg (67%); White solid; mp: 156.4e157.5 ꢀC; 1H NMR
13C NMR (151 MHz, CDCl3)
d 162.25, 160.20, 159.00, 151.24 and
(400 MHz, CDCl3)
d
8.62 (d, J ¼ 4.4 Hz, 1H), 8.53 (d, J ¼ 2.4 Hz, 1H),
149.61 (1JC-F ¼ 246 Hz), 150.70, 149.57, 136.56, 130.29 ꢁ 2, 129.42,
129.10 and 129.06 (3JC-F ¼ 6 Hz), 128.91 and 128.88 (4JC-F ¼ 3.0 Hz),
124.19 and 124.17 (4JC-F ¼ 2.0 Hz), 124.18 and 124.09 (2JC-
8.38 (dd, J ¼ 9.6, 2.4 Hz, 1H), 7.78 (d, J ¼ 9.6 Hz, 1H), 7.63 (dt, J ¼ 7.6,
1.6 Hz, 1H), 7.38 (d, J ¼ 8.8 Hz, 2H), 7.27 (d, J ¼ 7.6 Hz, 1H), 7.20 (dd,
J ¼ 6.8, 5.2 Hz, 1H), 7.07 (d,J ¼ 8.8 Hz, 2H), 6.77 (s, 1H), 4.75 (t,
J ¼ 8.0 Hz, 2H), 3.91 (s, 3H), 3.25 (t, J ¼ 8.0 Hz, 2H); 13C NMR
¼ 15.0 Hz), 123.61, 122.20 and 122.14 (3JC-F ¼ 9 Hz), 122.11, 121.66,
F
118.31 and 118.14 (2JC-F ¼ 25 Hz), 114.20 ꢁ 2, 55.54, 46.21 and 46.11
(4JC-F ¼ 15 Hz), 38.03 and 38.00 (5JC-F ¼ 4.0 Hz); MS (ESI) m/z 375
[MþH]þ; HRMS (ESI) calcd for C23H20FN2O2 [MþH]þ 375.1503,
found 375.1505.
(101 MHz, CDCl3)
d 161.64, 160.71, 157.98, 150.87, 149.76, 143.77,
142.07, 136.95, 130.27 ꢁ 2, 127.96, 125.41, 124.09, 123.88, 122.63,
122.19, 120.71, 115.67, 114.70 ꢁ 2, 55.61, 43.23, 35.87; MS (ESI) m/z
402 [MþH]þ; HRMS (ESI) calcd for C23H20N3O4 [MþH]þ 402.1448,
found 402.1450.
4.4. Experimental procedure for the synthesis of compound 4
4.3.19. 6-Chloro-4-(4-methoxyphenyl)-1-(2-(pyridin-2-yl)ethyl)
quinolin-2(1H)-one (3t)
Compound 1a (0.4 mmol), 15-iodo-vindoline (0.6 mmol),
Pd(OAc)2 (27 mg, 0.12 mmol), PPh3 (62 mg, 0.24 mmol),
Cu(OAc)2$H2O (160 mg, 0.8 mmol), Ag2CO3 (331 mg, 1.2 mmol) and
K2CO3 (166 mg, 1.2 mmol) were mixed in a flask and then toluene
(3 mL) was added as solvent. The reaction was refluxted for 11 h at
130 ꢀC. Then the mixture was filtrated with celite and the filtrate
was concentrated under reduced pressure. The residue was purified
by chromatograph on silica gel (petroleum ether/acetone/
TEA ¼ 300/60/1e300/100/1.3, v/v/v) to give compound 4 in 20%
yield. The compound 4 is a mixture of axially chiral biaryls, which
leads to the split of NMR.
Yield: 70 mg (45%); Light yellow solid; mp: 188.1e189.0 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
8.61 (d, J ¼ 4.0 Hz, 1H), 7.62 (d, J ¼ 9.2 Hz,
1H), 7.62 (dt, J ¼ 7.6, 2.0 Hz, 1H), 7.56 (d, J ¼ 2.0 Hz, 1H), 7.50 (dd,
J ¼ 9.2, 2.0 Hz, 1H), 7.35 (d, J ¼ 8.4 Hz, 2H), 7.27 (d, J ¼ 7.6 Hz, 1H),
7.18 (dd, J ¼ 7.6, 5.2 Hz, 1H), 7.04 (d, J ¼ 8.4 Hz, 2H), 6.68 (s, 1H), 4.68
(t, J ¼ 8.0 Hz, 2H), 3.89 (s, 3H), 3.23 (t, J ¼ 8.0 Hz, 2H); 13C NMR
(101 MHz, CDCl3)
d 161.53, 160.31, 158.45, 150.02, 149.66, 138.17,
136.83, 130.82, 130.26 ꢁ 2, 128.82, 127.61, 127.15, 123.86, 122.18,
122.13, 122.00, 116.36, 114.37 ꢁ 2, 55.55, 42.79, 35.94; MS (ESI) m/z
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075

8
C. Xiao et al. / Tetrahedron xxx (2016) 1e8
4.4.1. 4-(Vindoine-15-yl)-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-
one (4)
2013ZX09508104).
Yield: 57 mg (20%); Light yellow solid; mp: 214.7e216.9 ꢀC; 1H
Appendix A. Supplementary data
NMR (400 MHz, CDCl3)
d
9.64 (brs, 1H), 8.62 (d, J ¼ 3.6 Hz, 1H),
7.70e7.65 (m, 2H), 7.55 (t, J ¼ 7.6 Hz,1H), 7.35 (t, J ¼ 6.4 Hz,1H), 7.27
(d, J ¼ 8.0 Hz, 1H), 7.21 (t, J ¼ 6.0 Hz, 1H), 7.14e7.05 (m, 1H), 6.85 (s,
1H), 6.63 (s, 1 H), 6.55 (s, 1H), 6.18 (d, J ¼ 5.2 Hz 1H), 5.86e5.84 (m,
1H), 5.52 (d, J ¼ 6.0 Hz, 1H), 5.26e5.22 (m, 1H), 4.70 (q, J ¼ 7.6 Hz,
2H), 3.85 (s, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 3.53e3.41 (m, 2H), 3.27 (t,
J ¼ 7.6 Hz, 2H), 2.78 (s, 3H), 2.67 (1H), 2.48e2.31 (m, 2H), 2.10 (s,
2H), 2.09 (s, 1H), 1.96e1.71 (m, 1H), 1.17e1.13 (m, 1H), 0.53 (t,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2016.11.075.
References
1. (a) Kraus JM, Tatipaka HB, McGuffin SA, et al. J Med Chem. 2010;53:3887;
(b) Kumar N, Dhamija I, Raj PV, et al. Arab J Chem. 2014;7:409.
2. (a) Jayashree BS, Thomas S, Nayak Y. Med Chem Res. 2009;19:193;
(b) O'Donnell F, Smyth TJP, Ramachandran VN, Smyth WF. Int J Antimicrob Ag.
2010;35:30.
3. Freeman GA, Andrews III CW, Hopkins AL, et al. J Med Chem. 2004;47:5923.
4. Shiraiwa, M.; Ota, S.; Takefuchi, K.; Uchida, H.; Saegusa, M.; Mitsubori, T.;
Yoshizawa, M. JP Patent JP2003146972, 2003.
5. Rao S, Cunningham D, de Gramont A, et al. J Clin Oncol. 2004;22:3950.
6. El Abbadi N, Weniger B, Lobstein A, Quirion JC, Anton R. Planta Med. 1989;55:
603.
7. (a) Wu J, Xiang S, Zeng J, Leow M, Liu X-W. Org Lett. 2015;17:222;
(b) Ryabukhin DS, Gurskaya LY, Fukin GK, Vasilyev AV. Tetrahedron. 2014;70:
6428;
(c) Inamoto K, Saito T, Hiroya K, Doi T. J Org Chem. 2010;75:3900;
(d) Reddy MS, Thirupathi N, Babu MH. Eur J Org Chem. 2012:5803;
(e) Kobayashi K, Kitamura T, Yoneda K, Morikawa O, Konishi H. Chem Lett.
2000:798;
(f) Minville J, Poulin J, Dufresne C, Sturino CF. Tetrahedron Lett. 2008;49:3677.
8. Battistuzzi G, Bernini R, Cacchi S, De Salve I, Fabrizi G. Adv Synth Catal.
2007;349:297.
J ¼ 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 172.08, 171.96, 171.06,
170.93, 162.14, 158.59, 158.25, 158.23, 154.46, 154.29, 149.71, 149.33,
149.14, 149.11, 139.13, 139.05, 137.21, 130.68, 130.63, 130.39, 130.29,
128.42, 127.97, 124.94, 124.61, 124.41, 124.37, 124.30, 124.07, 122.05,
122.03, 121.94, 121.84, 121.76, 121.66, 121.33, 116.99, 116.80, 114.59,
114.56, 93.35, 83.62, 83.59, 79.67, 79.55, 76.51, 76.40, 67.43, 67.16,
55.83, 55.80, 53.02, 52.95, 52.50, 52.29, 51.98, 51.26, 51.12, 44.22,
44.08, 43.07, 42.99, 42.55, 38.36, 35.77, 31.26, 31.14, 29.83, 21.24,
8.01; MS (ESI): m/z 705 [MþH]þ; HRMS (ESI) calcd for C41H45N4O7
[MþH]þ 705.3283, found 705.3270.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (Grants: 81102329 and 81473110) and the
Chinese National Science & Technology Major Project “Key New
9. Wasa M, Yu J-Q. J Am Chem Soc. 2008;130:14058.
10. Inamoto K, Kawasaki J, Hiroya K, Kondo Y, Doi T. Chem Commun. 2012;48:4332.
11. (a) Johnson PD, Sohn JH, Rawal VH. J Org Chem. 2006;71:7899;
(b) Lewin G, Rolland Y, Poisson J. Heterocycles. 1980;14:1915.
Drug
Creation
and
Manufacturing
Program”
(Grant:
Please cite this article in press as: Xiao C, et al., Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)eH amidation reaction: An efficient route to
4-aryl-2-quinolinones, Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.11.075