An efficient route to quinoline-2-carboxylates via a rhodium-catalyzed oxidative [5+1] annulation of 2-vinylanilines with α-diazocarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2017.12.004

A novel rhodium-catalyzed oxidative [5 + 1] annulation of 2-vinylanilines with α-diazocarbonyl compounds for the construction of quinoline-2-carboxylate derivatives has been developed. A series of functional groups such as methyl, methoxy, fluoro, chloro, bromo, cyano, and even thienyl substituents were tolerated well. This methodology has the potential for use in the pharmaceutical industry.

Full text of DOI:10.1016/j.tet.2017.12.004

Tetrahedron 74 (2018) 348e353
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An efficient route to quinoline-2-carboxylates via a rhodium-catalyzed
oxidative [5þ1] annulation of 2-vinylanilines with
a-diazocarbonyl
compounds
Cong Wang, Qiuping Ding*, Qiang Zheng, Ping Bao, Yiyuan Peng
Key Laboratory of Small Functional Organic Molecule, Ministry of Education and Jiangxi's Key Laboratory of Green Chemistry, Jiangxi Normal University,
Nanchang, Jiangxi 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel rhodium-catalyzed oxidative [5 þ 1] annulation of 2-vinylanilines with
a-diazocarbonyl com-
Received 15 October 2017
Received in revised form
28 November 2017
Accepted 2 December 2017
Available online 5 December 2017
pounds for the construction of quinoline-2-carboxylate derivatives has been developed. A series of
functional groups such as methyl, methoxy, fluoro, chloro, bromo, cyano, and even thienyl substituents
were tolerated well. This methodology has the potential for use in the pharmaceutical industry.
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
2-Vinylaniline
a
-Diazocarbonyl
[5þ1] annulation
1. Introduction
(path e, Scheme 1),6 indoles (path f, Scheme 1),7 pyrroles (path g,
Scheme 1),8 and azepinone derivatives9 has received much atten-
a
-Diazocarbonyl are versatile C1 synthons in organic synthesis
tion. Despite these major advances, the preparation of quinoline
derivates via Rh-catalyzed CeH functionalization of 2-
-diazocarbonyl has not been reported (path h,
and have been extensively used in C-X (X ¼ C, O, S, N, etc.) bond
formation, particularly for the transition metal-catalyzed X-H
insertion of carbenoids. In general, nitrogen-containing directing
groups have been widely employed in CeH functionalizations for
the construction of N-heterocycles. For example, in 2015, Bolm
reported a rhodium-catalyzed CeH oxidative annulation and a
subsequent condensation process starting from NH-sulfoximines
a
vinylanilines with
Scheme 1).
a
Quinoline derivatives are important scaffolds due to their
presence in pharmaceutical compounds and their biological activ-
ity. Among them, quinoline-2-carboxylate derivatives have attrac-
ted considerable attention because of their potential anticancer,
anti-HIV, anti-inflammatory, antibacterial, and antituberculosis
activities,10 as well as for their use as biocompatible fluorescent
tags.11 The importance of quinoline-2-carboxylates has promoted
the rapid development of their synthesis. Two main synthetic
pathways can be used to construct such heterocycles: (i) metal-free
three component coupling of arylamines, glyoxylates and phenyl-
acetylenes12; (ii) cross-dehydrogenative coupling of N-aryl glycine
derivatives or iminoethyl glyoxylates with olefins, tetrahydrofurans
or alkynes.13 By extension, Palmieri et al. recently reported a het-
erogeneous one-pot synthesis quinoline-2-carboxylates via the
reaction of beta-nitroacrylates with 2-aminobenzaldehydes.14 In
addition, Sakai also reported an additional copper-catalyzed [5 þ 1]
annulation of 2-ethynylanilines with an N,O-acetal (Scheme 2, Eq.
1).15 Recently, we also reported several syntheses of functional-
ized quinoline derivatives via transition-metal-catalyzed oxidative
and
a-diazocarbonyl, effectively affording substituted 1,2-
benzothiazines (path a, Scheme 1).1 Kim and Lee independently
reported efficient strategies for the preparation of cinnolin-3(2H)-
one derivatives via a Rh-catalyzed direct CeH functionalization of
azobenzenes with the diazo derivative of Meldrum's acid (path b,
Scheme 1).2 Rh-catalyzed annulation reactions of primary benza-
mides with a-diazocarbonyl have been reported for the synthesis of
isoquinolinones (path c, Scheme 1)3 and isoindolones (path d,
Scheme 1).4 In addition, the synthesis of other useful N-heterocy-
cles via transition-metal-catalyzed CeH activation using diazo-
compounds as synthons, such as isoquinolines5 and its N-oxides
* Corresponding author.
E-mail address: dqpjxnu@gmail.com (Q. Ding).
https://doi.org/10.1016/j.tet.2017.12.004
0040-4020/© 2017 Elsevier Ltd. All rights reserved.

C. Wang et al. / Tetrahedron 74 (2018) 348e353
349
Table 1
Optimization of reaction conditionsa.
Entry
[Rh]
Oxidant
Base
Solvent
Yield (%)b
c
1
2
3
4
5
6
7
8
[Cp*RhCl2]2
Rh(acac)3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
O2
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DABCO
NEt3
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
toluene
THF
19
trace
15
33
40
trace
32
trace
38
32
15
40
67
20
15
11
50
55
60
c
c
RhCl(PPh3)3
c
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
BQd
DDQd
K2S2O8
AgOAc
CuCl2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
CuBr2
Scheme 1. Transition metal catalyzed transformation of
a-diazocarbonyl to N-
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
heterocycles.
tBuONa
NaHCO3
Cs2CO3
K2CO3
KF
Na2CO3
Na2CO3
Na2CO3
Na2CO3
70
76
50
30
12
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol, 2.0 equiv), [Rh] (5 mol%),
oxidant (0.4 mmol), base (0.4 mmol, 2.0 equiv), air, 100 ꢀC.
b
Isolated yield.
With AgSbF6 (20 mol%).
BQ: benzoquinone, DDQ: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
c
d
Na2CO3 proved to be beneficial for the reaction, with Na2CO3
providing the best yield (Table 1, entry 21, 76%). Further screening
of solvents showed that the reaction was highly dependent on the
solvent, and DCE was identified as the most suitable (Table 1, entry
21), and DCM, toluene, and THF afforded inferior yields (Table 1,
entries 22e24), whereas 1,4-dioxane, DMSO, and CH3CN only gave
trace amounts of desired product.
Next, we investigated the scope of substrates 1 in reactions with
diethyl 2-diazomalonate 2a under the optimal conditions (Table 2).
2-Vinylanilines 1 (R2 ¼ methyl) bearing electron-donating groups
(R1) such as methyl and methoxy underwent the oxidative [5 þ 1]
annulation smoothly to give the corresponding products (3b-d) in
moderate yields (40e53%). Substrates bearing an electron-
withdrawing group (R1), such as fluoro and bromo substituents,
provided the desired products (3e-i) in satisfactory yields
(48e76%). We then conducted the reaction of several 2-(1-
arylvinyl)anilines 1 (R2 ¼ aryl) under the same reaction condi-
tions. Predictably, 2-(1-phenylvinyl)aniline and various 2-(1-
arylvinyl)anilines bearing electron-withdrawing substituents (F
and Cl) at the aryl moiety of R2 provided the desired products 3j-m
in good to excellent yields (71e92%). Electron-donating sub-
stituents (Me and OMe) at the R2 of the 2-(1-arylvinyl)anilines led
to the corresponding products 3n-p in moderate yields (57e64%).
Scheme 2. Approach to construct quinoline skeleton.
annulation reactions.16a-d Furthermore, our group16d and the Ji16e
group separately disclosed the synthesis of 2-aminoquinolines via
an intermolecular oxidative annulation of 2-vinylanilines with
isocyanides (Scheme 2, Eq. 2). Consequently, we considered the
possibility that quinoline derivatives could be prepared via the
reaction of 2-vinylanilines with a-diazocarbonyl (Scheme 2, Eq. 3).
2. Results and discussion
We initiated our studies by exploring the reaction of 2-
vinylanilines 1a with diethyl 2-diazomalonate 2a using
a
[RhCp*Cl2]2 and AgSbF6 catalytic system. To our delight, the desired
product, quinoline-2-carboxylate 3a was obtained in 19% yield in
DCE using DBU as a base (Table 1, entry 1). Encouraged by this
result, the effects of different [Rh] catalysts were examined (Table 1,
entries 1e4), and Rh2(OAc)4 provided the best result (33% yield,
Table 1, entry 4). We were pleased to obtain the desired product 3a
in 40% yield in the absence of AgSbF6 (Table 1, entry 5). Screening of
oxidants showed that Cu(OAc)2 was found to be the best for this
reaction, giving 3a in 67% yield (Table 1, entry 13), while other
oxidants such as O2, benzoquinone (BQ), 3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ), K2S2O8, AgOAc, CuCl2 and CuBr2 were all
less effective (Table 1, entries 6e12). Subsequently, a variety of
bases were investigated to improve the reaction efficiency (Table 1,
entries 14e21). Some bases such as NaHCO3, Cs2CO3, K2CO3, KF, and
Remarkably,
a substrate bearing a heterocyclic substituent
(R2 ¼ thienyl) was compatible with the present catalytic system,
affording the product 3q in 50% yield.
Subsequently, the scope of the a-diazocarbonyl 2 was examined
(Scheme 3). Dimethyl 2-diazomalonate 2b underwent smooth
annulation under the standard conditions, and obtained the
desired product 3r in 55% yield (Scheme 3, Eq. 1). Correspondingly,

350
C. Wang et al. / Tetrahedron 74 (2018) 348e353
Table 2
unsymmetrical diazo
compound ethyl 2-diazo-3-oxo-3-
Rhodium-catalyzed oxidative [5 þ 1] annulation of 2-vinylanilines 1 with
a-diazo-
phenylpropanoate 2e reacted with 2-vinylaniline 1a to afford the
product 3a in 45% yield (Scheme 3, Eq. 2).
carbonyl 2a.
Based on previous reports17 and our control experiments
(Scheme 4), a plausible mechanism for the Rh-catalyzed oxidative
[5 þ 1] annulation is illustrated in Scheme 5. Firstly, the nitrogen
atom of aniline 1 adds to the active Rh(III) species to afford inter-
mediate A bearing a RheN bond. Secondly, coordination, deni-
trogenation and insertion of
a-diazocarbonyl 2 leads to Rh(III)
carbenoid B. Thirdly, the 1,2-migration of the Rh(III) carbenoid into
the NeRh bond generates the CeN bond, and the following coor-
dination of the carbon-carbon double bond to Rh(III) leads to in-
termediate C. Fourthly, alkene insertion into the RheC bond of
Rh(III) species C gives an alkyl rhodium intermediate D, which
undergoes b-hydride elimination to generate the product 3′ and
Rh(I), which was reoxidized by Cu(II) and air to give the active
Rh(III) species. Finally, quinoline 3 is formed from 3′ via decar-
balkoxylation/aromatization18 with Cu(OAc)2/air system, which
were demonstrated by control experiment (Scheme 4, Eq. 2).
3. Conclusion
In summary, we have developed an effective method for the
synthesis of substituted quinoline-2-carboxylates 3 via a rhodium-
catalyzed oxidative [5 þ 1] annulation of 2-vinylanilines 1 with
a-
diazocarbonyl 2. This transformation is applicable to a wide range
of 2-vinylanilines 1 affording diverse target products in moderate
to excellent yields. The proposed mechanism involves
a
rhodium(III)-catalyzed oxidative [5 1] annulation. Further
þ
mechanistic studies concerning this transformation and its appli-
cation to the construction of other heterocycles using this catalytic
system are currently underway in our laboratory.
4. Experimental
4.1. General
4.1.1. General procedure for rhodium-catalyzed oxidative [5 þ 1]
annulation of 2-vinylanilines with diazo compounds
To a 25 mL tube containing a magnetic stir bar, was added 2-
vinylanilines 1 (0.2 mmol), Rh2(OAc)4 (0.01 mmol, 5 mol%),
isopropyl and benzyl 2-diazomalonates 2c and 2d provided the
desired products 3s and 3t in moderate yields (Scheme 3, Eq.1). The
Scheme 3. Scope of
a
-diazocarbonyl compounds.

C. Wang et al. / Tetrahedron 74 (2018) 348e353
351
Scheme 4. Control experiments.
Scheme 5. Possible mechanism of Rh-catalyzed oxidative [5 þ 1] annulation.
Cu(OAc)2 (0.4 mmol, 2.0 equiv), Na2CO3 (0.4 mmol, 2.0 equiv), 1,2-
DCE (2 mL), and -diazocarbonyl compounds 2 (0.4 mmol, 2 equiv).
C14H16NO2: 230.1176, found: 230.1171.
a
The resulting mixture was stirred at 100 ꢀC in air in sealed tube for
16 h. After being cooled to room temperature, the reaction was
monitored by TLC and the solvent was evaporated under reduced
pressure. Purification was carried out by column chromatography
using a mixture of ethyl acetate and petroleum ether (1:10 to 1:20)
as eluent to obtain the desired product 3.
4.1.1.3. Ethyl 4,6-dimethylquinoline-2-carboxylate (3c). Isolated
(Rf ¼ 0.5, EtOAc e petroleum ether ¼ 1:20) as a yellow oil (18.3 mg,
40% yield), 1H NMR (400 MHz, CDCl3)
d
8.20 (d, J ¼ 8.4 Hz, 1H), 8.01
(s, 1H), 7.78 (s, 1H), 7.60 (d, J ¼ 8.4 Hz, 1H), 4.55 (q, J ¼ 7.2 Hz, 2H),
2.75 (s, 3H), 2.59 (s, 3H), 1.49 (t, J ¼ 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3)
d 165.8, 146.9, 145.9, 144.9, 138.6, 132.1, 131.1, 129.3, 122.7,
121.8, 62.2, 22.1, 18.9, 14.4. HRMS (ESI): m/z [M þ H]þ calcd for
4.1.1.1. Ethyl
(Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow oil (32.5 mg,
76% yield), 1H NMR (400 MHz, CDCl3)
4-methylquinoline-2-carboxylate
(3a). Isolated
C14H16NO2: 230.1176, found: 230.1171.
d
8.32 (d, J ¼ 8.0 Hz, 1H), 8.05
4.1.1.4. Ethyl 6-methoxy-4-methylquinoline-2-carboxylate (3d).
19a Isolated (Rf ¼ 0.7, EtOAc e petroleum ether ¼ 1:10) as a yellow
(d, J ¼ 7.6 Hz,1H), 8.04 (S,1H), 7.78 (t, J ¼ 7.6 Hz,1H), 7.68 (dt, J ¼ 1.2,
7.6 Hz, 1H), 4.56 (q, J ¼ 7.2 Hz, 2H), 2.79 (s, 3H), 1.50 (t, J ¼ 7.2 Hz,
oil (24.0 mg, 49% yield), 1H NMR (400 MHz, CDCl3)
d 8.21 (d,
3H). 13C NMR (100 MHz, CDCl3)
d
165.7, 147.9, 147.4, 145.9, 131.4,
J ¼ 9.3 Hz, 1H), 8.02 (s, 1H), 7.41 (dd, J ¼ 2.8, 9.2 Hz, 1H), 7.19 (d,
129.8, 129.3, 128.3, 123.7, 121.7, 62.2, 18.9 14.4. HRMS (ESI): m/z
J ¼ 1.6 Hz, 1H), 4.54 (q, J ¼ 7.2 Hz, 2H), 3.98 (s, 3H), 2.72 (s, 3H), 1.49
[M þ H]þ calcd for C13H14NO2: 215.0946, found: 215.0953.
(t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 165.8, 159.2, 145.3,
143.9, 143.4, 133.0, 130.6, 122.5, 122.1, 101.4, 62.1, 55.6, 19.1, 14.4.
HRMS (ESI): m/z [M þ H]þ calcd for C14H16NO3: 246.1125, found:
246.1133.
4.1.1.2. Ethyl 4,7-dimethylquinoline-2-carboxylate (3b). Isolated
(Rf ¼ 0.3, EtOAc e petroleum ether ¼ 1:10) as a yellow oil (24.3 mg,
53% yield), 1H NMR (400 MHz, CDCl3)
d 8.09 (s, 1H), 7.97 (s, 1H), 7.92
(d, J ¼ 8.4 Hz, 1H), 7.49 (d, J ¼ 8.4 Hz, 1H), 4.55 (q, J ¼ 7.2 Hz, 2H),
4.1.1.5. Ethyl
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow oil
(30.3 mg, 65% yield), 1H NMR (400 MHz, CDCl3)
8.32 (dd, J ¼ 5.6,
9.2 Hz, 1H), 8.06 (s, 1H), 7.63 (dd, J ¼ 2.4, 9.6 Hz, 1H), 7.59e7.50 (m,
8-fluoro-4-methylquinoline-2-carboxylate
(3e).
2.75 (s, 3H), 2.57 (s, 3H), 1.49 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3)
d
165.8, 147.8, 147.7, 145.6, 140.2, 130.6, 130.3, 127.4, 123.3,
d
121.0, 62.2, 21.7, 18.9, 14.4. HRMS (ESI): m/z [M þ H]þ calcd for

352
C. Wang et al. / Tetrahedron 74 (2018) 348e353
2
1H), 4.56 (q, J ¼ 7.2 Hz, 2H), 2.74 (s, 3H), 1.50 (t, J ¼ 7.2 Hz, 3H). 13
C
125.4, 121.3, 115.8 (d, JC-F ¼ 21.5 Hz), 62.4, 14.4. HRMS (ESI): m/z
1
NMR (100 MHz, CDCl3)
d
165.5, 161.7 (d, JC-F ¼ 249.7 Hz), 147.4,
[M þ H]þ calcd for C18H15FNO2: 296.1081, found: 296.1085.
145.3144.5, 134.1 (d, 3JC-F ¼ 9.4 Hz), 130.4 (d, 3JC-F ¼ 9.7 Hz), 122.2,
2
120.3 (d, 2JC-F ¼ 25.7 Hz), 107.4 (d, JC-F ¼ 22.3 Hz), 62.3, 19.0, 14.4.
4.1.1.12. Ethyl
4-(4-chlorophenyl)quinoline-2-carboxylate
(3l).
HRMS (ESI): m/z [M þ H]þ calcd for C13H13FNO2: 234.0925, found:
19d Isolated (Rf ¼ 0.5, EtOAc e petroleum ether ¼ 1:20) as a yellow
234.0929.
soild (44.1 mg, 71% yield), mp: 126e128 ꢀC. 1H NMR (400 MHz,
CDCl3)
d
8.39 (d, J ¼ 8.8 Hz, 1H), 8.11 (s, 1H), 7.93 (d, J ¼ 8.4 Hz, 1H),
4.1.1.6. Ethyl
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:20) as a yellow oil
(34.5 mg, 74% yield), 1H NMR (400 MHz, CDCl3)
7-fluoro-4-methylquinoline-2-carboxylate
(3f).
7.81 (t, J ¼ 7.8 Hz, 1H), 7.62 (t, J ¼ 7.6 Hz,1H), 7.57e7.48 (m, 2H), 7.25
(t, J ¼ 8.6 Hz, 2H), 4.58 (q, J ¼ 7.2 Hz, 2H), 1.50 (t, J ¼ 7.2 Hz, 3H). 13
C
d
8.05 (dd, J ¼ 6.0,
NMR (100 MHz, CDCl3) d 165.5, 164.3, 161.8, 148.7, 148.2, 147.8,
9.2 Hz, 1H), 8.00 (s, 1H), 7.94 (dd, J ¼ 2.4, 10.0 Hz, 1H), 7.46 (dt,
133.5, 131.4, 131.3, 130.1, 128.8, 127.7, 125.4, 121.3, 115.9, 115.7, 62.4,
14.4. HRMS (ESI): m/z [M þ H]þ calcd for C18H15ClNO2: 312.0786,
found: 312.0789.
J ¼ 2.4, 9.2 Hz, 1H), 4.56 (q, J ¼ 7.2 Hz, 2H), 2.78 (s, 3H), 1.50 (t,
1
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
165.4, 163.1 (d, JC-
¼ 249.5 Hz), 149.0, 148.7 (d,3JC-F ¼ 12.6 Hz), 146.2, 126.4, 125.9 (d,
F
3JC-F ¼ 9.8 Hz), 121.2, 118.8 (d, JC-F ¼ 25.2 Hz), 114.6 (d,2JC-
4.1.1.13. Ethyl
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow solid
(51.9 mg, 88%), mp: 125e126 ꢀC. 1H NMR (400 MHz, CDCl3)
8.40
4-(3-fluorophenyl)quinoline-2-carboxylate
(3m).
2
¼ 20.0 Hz), 62.4, 19.0, 14.4. HRMS (ESI): m/z [M þ H]þ calcd for
F
C
13H13FNO2: 234.0925, found: 234.0929.
d
(d, J ¼ 8.8 Hz, 1H), 8.13 (s, 1H), 7.94 (d, J ¼ 8.8 Hz, 1H), 7.81 (t,
4.1.1.7. Ethyl
Isolated (Rf ¼ 0.7, EtOAc e petroleum ether ¼ 1:10) as a yellow oil
(27.5 mg, 59% yield), 1H NMR (400 MHz, CDCl3)
6-fluoro-4-methylquinoline-2-carboxylate
(3g).
J ¼ 7.6 Hz, 1H), 7.63 (t, J ¼ 7.6 Hz, 1H), 7.56e7.49 (m, 1H), 7.32 (d,
J ¼ 7.6 Hz, 1H), 7.28e7.20 (m, 2H), 4.58 (q, J ¼ 7.2 Hz, 2H), 1.50 (t,
1
d
8.24 (dd, J ¼ 5.6,
J ¼ 7.2 Hz, 3H)$13C NMR (100 MHz, CDCl3)
d
165.3, 162.8 (d, JC-
3
9.2 Hz,1H), 7.98 (s,1H), 7.54 (dd, J ¼ 2.4, 9.6 Hz,1H), 7.47 (dd, J ¼ 2.8,
8.4 Hz, 1H), 4.48 (q, J ¼ 7.2 Hz, 2H), 2.65 (s, 3H), 1.42 (t, J ¼ 7.2 Hz,
¼ 246.2 Hz), 148.3, 148.2, 147.8, 139.6 (d, JC-F ¼ 7.9 Hz), 131.3,
F
130.4,130.3,130.1,128.9,127.4,125.3,121.2,116.6 (d, 2JC-F ¼ 22.2 Hz),
115.7 (d, 2JC-F ¼ 20.8 Hz), 62.3, 14.4. HRMS (ESI): m/z [M þ H]þ calcd
for C18H15FNO2: 296.1081, found: 296.1085.
3H). 13C NMR (100 MHz, CDCl3)
d
164.4, 160.6 (d, 1JC-F ¼ 249.7 Hz),
146.3, 144.2, 143.5, 133.0 (d, 3JC-F ¼ 9.5 Hz), 129.3 (d, 3JC-F ¼ 9.6 Hz),
121.2, 119.2 (d, 2JC-F ¼ 25.7 Hz), 106.3 (d, 2JC-F ¼ 22.3 Hz), 61.2, 17.9,
13.4. HRMS (ESI): m/z [M þ H]þ calcd for C13H13FNO2: 234.0925,
found: 234.0929.
19d
4.1.1.14. Ethyl 4-(p-tolyl)quinoline-2-carboxylate (3n).
Isolated
(Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow oil (37.2 mg,
64%). 1H NMR (400 MHz, CDCl3)
d
8.37 (d, J ¼ 8.4 Hz, 1H), 8.13 (s,
4.1.1.8. Ethyl
6-bromo-4-methylquinoline-2-carboxylate
(3h).
1H), 8.00 (d, J ¼ 8.4 Hz, 1H), 7.78 (t, J ¼ 7.6 Hz, 1H), 7.59 (t, J ¼ 7.6 Hz,
1H), 7.44 (d, J ¼ 8.0 Hz, 2H), 7.36 (d, J ¼ 8.0 Hz, 2H), 4.57 (q,
J ¼ 7.2 Hz, 2H), 2.48 (s, 3H), 1.49 (t, J ¼ 7.2 Hz, 3H). 13C NMR
19b Isolated (Rf ¼ 0.6, EtOAc e petroleum ether ¼ 1:20) as a yellow
soild (44.5 mg, 76% yield). 1H NMR (400 MHz, CDCl3)
d 8.18 (d,
J ¼ 2.0 Hz, 1H), 8.16 (d, J ¼ 9.2 Hz, 1H), 8.03 (s, 1H), 7.83 (dd, J ¼ 2.0,
(100 MHz, CDCl3) d 165.5, 149.9, 148.2, 147.8, 138.7, 134.6, 131.2,
9.2 Hz, 1H), 4.55 (q, J ¼ 7.1 Hz, 2H), 2.74 (s, 3H), 1.49 (t, J ¼ 7.2 Hz,
129.9, 129.5, 129.4, 128.4, 127.9, 125.8, 121.2, 62.2, 21.3, 14.4. HRMS
3H). 13C NMR (100 MHz, CDCl3)
d
165.3, 148.2, 146.0, 145.0, 133.4,
(ESI): m/z [M þ H]þ calcd for C19H18NO2: 292.1332, found: 292.1340.
133.0, 130.4, 126.2, 122.9, 122.4, 62.3, 18.8, 14.4. HRMS (ESI): m/z
[M þ H]þ calcd for C13H13BrNO2: 294.0124, found: 294.0130.
4.1.1.15. Ethyl
(Rf ¼ 0.5, EtOAc e petroleum ether ¼ 1:10) as a yellow solid
(33.2 mg, 57%), mp: 80e82 ꢀC. 1H NMR (400 MHz, CDCl3)
8.39 (d,
4-(o-tolyl)quinoline-2-carboxylate
(3o). Isolated
4.1.1.9. Ethyl
6-cyano-4-methylquinoline-2-carboxylate
(3i).
d
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a white soild
J ¼ 8.8 Hz, 1H), 8.07 (s, 1H), 7.80e7.76 (m, 1H), 7.58e7.52 (m, 2H),
7.45e7.32 (m, 3H), 7.23 (d, J ¼ 7.6 Hz, 1H), 4.57 (q, J ¼ 7.2 Hz, 2H),
2.03 (s, 3H), 1.49 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
(22.4 mg, 48% yield), mp: 167e169 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.45 (s, 1H), 8.39 (d, J ¼ 8.8 Hz, 1H), 8.13 (s, 1H), 7.91 (dd, J ¼ 1.6,
8.8 Hz, 1H), 4.57 (q, J ¼ 7.2 Hz, 2H), 2.83 (s, 3H), 1.50 (t, J ¼ 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3)
164.9, 150.6, 148.5, 146.8, 132.8,
d
165.5, 149.9, 147.9, 137.0, 136.0, 131.1, 130.3, 130.0, 129.5, 128.7,
d
128.6, 128.3, 125.9, 125.8, 121.4, 62.2, 20.0, 14.4. HRMS (ESI): m/z
130.4, 130.2, 128.7, 123.1, 118.4, 111.9, 62.6, 18.8, 14.3. HRMS (ESI): m/
[M þ H]þ calcd for C19H18NO2: 292.1332, found: 292.1340.
z [M þ H]þ calcd for C14H12N2O2: 240.2620, found: 240.2628.
4.1.1.16. Ethyl 4-(2-methoxyphenyl)quinoline-2-carboxylate (3p).
Isolated (Rf ¼ 0.3, EtOAc e petroleum ether ¼ 1:10) as a white solid
19c
4.1.1.10. Ethyl 4-phenylquinoline-2-carboxylate (3j).
Isolated
(Rf ¼ 0.7, EtOAc e petroleum ether ¼ 1:10) as a yellow soild
(38.0 mg, 62%), mp: 110e112 ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.36
(50.9 mg, 92% yield), mp 115e119 ꢀC. 1H NMR (400 MHz, CDCl3)
(d, J ¼ 8.4 Hz, 1H), 8.12 (s, 1H), 7.75 (t, J ¼ 7.6 Hz, 1H), 7.65 (d,
J ¼ 8.4 Hz, 1H), 7.57e7.46 (m, 2H), 7.32e7.26 (m, 1H), 7.12 (t,
J ¼ 7.6 Hz,1H), 7.08 (d, J ¼ 8.4 Hz,1H), 4.56 (q, J ¼ 7.2 Hz, 2H), 3.71 (s,
d
8.30 (d, J ¼ 8.8 Hz, 1H), 8.06 (s, 1H), 7.89 (d, J ¼ 8.4 Hz, 1H), 7.70 (t,
J ¼ 7.3 Hz, 1H), 7.51 (t, J ¼ 7.6 Hz, 1H), 7.47e7.41 (m, 5H), 4.49 (q,
J ¼ 7.2 Hz, 2H), 1.41 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
3H),1.48 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 165.6,156.7,
d
165.5, 149.8, 148.2, 147.8, 137.5, 131.2, 130.0, 129.6, 128.8, 128.7,
147.8, 147.2, 131.2, 130.9, 130.3, 129.7, 128.5, 128.1, 126.4,126.2,122.1,
128.6, 127.8, 125.7, 121.3, 62.3, 14.4. HRMS (ESI): m/z [M þ H]þ calcd
120.7, 111.1, 99.9, 62.1, 55.5, 14.4. HRMS (ESI): m/z [M þ H]þ calcd for
for C18H16NO2: 278.1176, found: 278.1173.
C19H18NO3: 308.1281, found: 308.1284.
4.1.1.11. Ethyl
4-(4-fluorophenyl)quinoline-2-carboxylate
(3k).
4.1.1.17. Ethyl
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a white solid
(28.3 mg, 50%), mp: 127e129 ꢀC, 1H NMR (400 MHz, CDCl3)
8.36
4-(thiophen-2-yl)quinoline-2-carboxylate
(3q).
19c Isolated (Rf ¼ 0.6, EtOAc e petroleum ether ¼ 1:10) as a yellow
soild (50.2 mg, 85% yield), mp 116e118 ꢀC. 1H NMR (400 MHz,
d
CDCl3)
d
8.39 (d, J ¼ 8.8 Hz, 1H), 8.12 (s, 1H), 7.93 (d, J ¼ 8.4 Hz, 1H),
(t, J ¼ 8.8 Hz, 2H), 8.24 (s, 1H), 7.83 (t, J ¼ 8.4 Hz, 1H), 7.67 (t,
7.80 (t, J ¼ 8.2 Hz,1H), 7.62 (t, J ¼ 8.2 Hz,1H), 7.55e7.49 (m, 2H), 7.25
J ¼ 7.6 Hz, 1H), 7.57 (d, J ¼ 4.8 Hz, 1H), 7.44 (d, J ¼ 3.6 Hz, 1H),
(t, J ¼ 8.6 Hz, 2H), 4.58 (q, J ¼ 7.2 Hz, 2H), 1.50 (t, J ¼ 7.2 Hz, 3H). 13
C
7.28e7.24 (m, 1H), 4.58 (q, J ¼ 7.2 Hz, 2H), 1.50 (t, J ¼ 7.2 Hz, 3H). 13
C
NMR (100 MHz, CDCl3)
d
165.45 (s), 163.1 (d, 1JC-F ¼ 247.2 Hz), 148.7,
NMR (100 MHz, CDCl3) d 165.3, 148.4, 147.8, 142.2, 138.4, 131.3,
148.2, 147.8, 133.5 (d, 3JC-F ¼ 3.4 Hz), 131.4, 131.3, 130.1, 128.8, 127.7,
130.1, 129.0, 128.9, 127.9, 127.8, 127.4, 125.4, 121.6, 62.3, 14.4. HRMS

C. Wang et al. / Tetrahedron 74 (2018) 348e353
353
(ESI): m/z [M þ H]þ calcd for C16H14NO2S: 284.0740, found:
127.9, 126.5, 119.4, 118.7, 116.7, 114.1, 66.7, 53.4. HRMS (ESI): m/z
[M þ H]þ calcd for C17H13NO2: 324.3555, found: 324.3553.
284.0734.
19d
4.1.1.18. Methyl 4-phenylquinoline-2-carboxylate (3r).
Isolated
Acknowledgement
(Rf ¼ 0.3, EtOAc e petroleum ether ¼ 1:10) as a yellow solid
(29.0 mg, 55%), mp: 101e102 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.38
Financial Supported from National Natural Science Foundation
of China (21662017, 21262016), and Natural Science Foundation of
Jiangxi Province of China (20133ACB20008, 20171BAB2030007) is
gratefully acknowledged. We thank Siyun Editing Co., Ltd for lin-
guistic assistance during the preparation of our manuscript.
(d, J ¼ 8.4 Hz, 1H), 8.16 (s, 1H), 7.98 (d, J ¼ 8.4 Hz, 1H), 7.80 (t,
J ¼ 7.6 Hz,1H), 7.60 (t, J ¼ 7.6 Hz, 1H), 7.57e7.50 (m, 5H), 4.10 (s, 3H).
13C NMR (100 MHz, CDCl3)
d 166.1, 149.9, 148.2, 147.5, 137.5, 131.1,
130.1, 129.6, 128.8, 128.7, 128.7, 127.9, 125.8, 121.3, 53.2. HRMS (ESI):
m/z [M þ H]þ calcd for C17H13NO2: 264.3035, found: 264.3033.
4.1.1.19. Isopropyl
Isolated (Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a white solid
(27.9 mg, 48%), mp: 104e107 ꢀC. 1H NMR (400 MHz, CDCl3)
8.39
4-phenylquinoline-2-carboxylate
(3s).
Appendix A. Supplementary data
d
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2017.12.004.
(d, J ¼ 8.8 Hz, 1H), 8.08 (s, 1H), 7.95 (d, J ¼ 8.0 Hz, 1H), 7.78 (t,
J ¼ 7.8 Hz, 1H), 7.61e7.50 (m, 6H), 5.41 (dt, J ¼ 6.4, 12.4 Hz, 1H), 1.48
(s, 3H), 1.46 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 164.9, 149.7, 148.3,
References and notes
148.2, 137.7, 131.3, 129.9, 129.6, 128.7, 128.5, 127.7, 125.6, 121.2, 69.9,
21.9. HRMS (ESI): m/z [M þ H]þ calcd for C17H13NO2: 292.3575,
found: 292.3579.
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(b) Phatake R-S, Patel P, Ramana CV. Org Lett. 2016;18:2828;
4.1.1.20. Benzyl
4-phenylquinoline-2-carboxylate
(3t). Isolated
(Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow soild
(c) Kim JH, Grebes S, Glorius F. Angew Chem Int Ed. 2016;55:5577.
(30.6 mg, 45% yield). mp: 94e97 ꢀC. 1H NMR (400 MHz, CDCl3)
4. Hyster TK, Ruhl KE, Rovis T. J Am Chem Soc. 2013;135:5364.
5. Li J, Tang M, Zang L, Zhang X, Zhang Z, Ackermann L. Org Lett. 2016;18:2742.
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7. (a) Mishra NK, Choi M, Jo H, et al. Chem Commun. 2015;51:17229;
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(e) Qi Z, Yu S, Li X. Org Lett. 2016;18:700;
d
8.38 (d, J ¼ 8.4 Hz, 1H), 8.12 (s, 1H), 7.96 (d, J ¼ 8.4 Hz, 1H), 7.79 (t,
J ¼ 7.6 Hz,1H), 7.60 (t, J ¼ 7.6 Hz,1H), 7.53 (m, 6H), 7.37 (m, 4H), 5.55
(s, 2H). 13C NMR (100 MHz, CDCl3)
165.3, 149.9, 148.3, 137.6, 135.7,
d
131.3, 130.0, 129.6128.7, 128.7, 128.6, 128.6, 128.6, 127.9, 125.7, 121.3,
67.7. HRMS (ESI): m/z [M þ H]þ calcd for C17H13NO2: 340.4015,
found: 340.4008.
(f) Tang G-D, Pan C-L, Li X. Org Chem Front. 2016;3:87.
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1960;
4.1.1.21. methyl 4-methylquinoline-2-carboxylate (3u). Isolated
(Rf ¼ 0.4, EtOAc e petroleum ether ¼ 1:10) as a yellow soild
(30.6 mg, 45% yield). mp: 75e79 ꢀC.1H NMR (400 MHz, CDCl3)
(b) Manfredini S, Vertuani S, Pavan B, et al. Bioorg Med Chem. 2004;12:5453;
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Chem. 1999;9:2607;
d
8.31 (d, J ¼ 8.4 Hz, 1H), 8.05 (d, J ¼ 7.6 Hz, 2H), 7.78 (t, J ¼ 7.6 Hz,
1H), 7.67 (t, J ¼ 7.6 Hz, 1H), 4.08 (s, 3H), 2.79 (s, 3H). 13C NMR
(e) Corey EJ, Tramontano A. J Am Chem Soc. 1981;103:5599.
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2013;4:1461.
(100 MHz, CDCl3)
d 166.2, 147.6, 147.4, 145.9, 131.4, 129.9, 128.4,
123.7, 121.7, 53.1, 18.9. HRMS (ESI): m/z [M þ H]þ calcd for
C
14H16NO4: 262.1074, found: 262.1081.
~
13. (a) Rohlmann R, Stopka T, Richter H, Mancheno OGJ. Org Chem. 2013;78:6050;
4.1.2. Procedure for the synthesis of dimethyl 4-phenylquinoline-
2,2(1H)-dicarboxylate (3r’)
To a 25 mL tube containing a magnetic stir bar, was added 2-
vinylanilines 1r (0.2 mmol), Rh2(OAc)4 (0.01 mmol, 5 mol%),
Cu(OAc)2 (0.4 mmol, 2.0 equiv), Na2CO3 (0.4 mmol, 2.0 equiv), 1,2-
(b) Liu G, Qian J, Hua J, Cai F, Li X, Liu L. Org Biomol Chem. 2016;14:1147;
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(g) Liu P, Wang Z, Lin J, Hu X. Eur J Org Chem. 2012:1583;
DCE (2 mL), and
a-diazocarbonyl compounds 2b (0.4 mmol, 2
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equiv). The resulting mixture was stirred at 100 ꢀC in N2 in sealed
tube for 16 h. After being cooled to room temperature, the reaction
was monitored by TLC and the solvent was evaporated under
reduced pressure. Purification was carried out by column chro-
matography using a mixture of ethyl acetate and petroleum ether
(1:10) as eluent to obtain the desired product 3r’.
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~
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2374.
4.1.3. Dimethyl 4-phenylquinoline-2,2(1H)-dicarboxylate (3r’)
Isolated (Rf ¼ 0.5, EtOAc e petroleum ether ¼ 1:10) as a yellow
18. (a) Im YJ, Lee KY, Kim TH, Kim JN. Tetrahedron Lett. 2002;43:4675;
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2016;3:412;
oil (38.1 mg, 59%). 1H NMR (400 MHz, CDCl3)
d 7.36e7.23 (m, 5H),
7.00 (t, J ¼ 7.6 Hz, 1H), 6.84 (d, J ¼ 7.6 Hz, 1H), 6.65 (d, J ¼ 7.6 Hz,1H),
(b) Bass JY, Caravella JA, Chen L-Y, et al. Synthesis. 2001;7:1098;
(c) Liu G-L, Qian J-R, Hua J, Cai F, Li X, Liu L. Org Biomol Chem. 2016;14:1147;
(d) Wu Y-C, Liu L, Li H-J, Wang D, Chen Y-J. J Org Chem. 2006;71:6592.
6.55 (t, J ¼ 7.6 Hz, 1H), 5.89 (s, 1H), 5.10 (s, 1H), 3.71 (s, 6H). 13C NMR
(100 MHz, CDCl3)
d 169.7, 141.5, 139.7, 138.4, 129.6, 128.9, 128.3,