Copper-Catalyzed Deoxygenative C2-Sulfonylation of Quinoline N -Oxides with DABSO and Phenyldiazonium Tetrafluoroborates for the Synthesis of 2-Sulfonylquinolines via a Radical Reaction

Article abstract of DOI:10.1055/s-0037-1611787

An efficient and practical method for the synthesis of 2-sulfonylquinolines through copper-catalyzed deoxygenative C2-sulfonylation of quinoline N -oxides with 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) and phenyldiazonium tetrafluoroborates is demonstrated. Products with various substituents were obtained in moderate to high yields.

Full text of DOI:10.1055/s-0037-1611787

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–G
paper
A
en
G.-H. Li et al.
Paper
Synthesis
Copper-Catalyzed Deoxygenative C2-Sulfonylation of Quinoline
N-Oxides with DABSO and Phenyldiazonium Tetrafluoroborates
for the Synthesis of 2-Sulfonylquinolines via a Radical Reaction
Guang-Hui Lia◊
Dao-Qing Donga◊
Qi Dengb
N2BF4
CuOTf (10 mol%)
O
Shi-Qiang Yanc
Zu-Li Wang*a
+
DABSO
+
CH2Cl2, 100 °C
N
S
R2
R1
N
O
0
0
0
0-0
0
0
2-3
5
0
3-
4
0
9
7
R1
R2
O
18 examples, 60–88% yield
a College of Chemistry and Pharmaceutical Sciences,
Qingdao Agricultural University, Qingdao 266109,
P. R. of China
wangzulichem@163.com
wangzuli09@tsinghua.org.cn
b School of Chemistry and Chemical Engineering, Hunan
University of Science and Technology, Xiangtan
411201, P. R. of China
c Shandong Dyne Marine Biopharmaceutical Co., Ltd.,
Weihai, Shandong 264300, P. R. of China
◊ These authors contributed equally to this article.
Received: 14.02.2019
Accepted after revision: 14.03.2019
Published online: 15.05.2019
sulfonyl chlorides (electrophile), were proposed in the
mechanism (Scheme 1a).4 W.-M. He’s group5 found that de-
oxygenative sulfonylation of quinoline N-oxides using sul-
fonyl chlorides could also be realized under metal-free con-
ditions. Without employing any base and organic solvent,
various functionalized 2-sulfonylquinolines were obtained
under ultrasound conditions.5a Besides sulfonyl chlorides,
sulfonyl hydrazides have proved to be good partners for the
preparation of 2-sulfonylquinolines. In 2016, C.-L. He’s
group (Scheme 1b)6 and Zeng’s group7 independently dis-
closed the reaction of quinoline N-oxides with sulfonyl hy-
drazides, and a series of the corresponding products was ef-
ficiently obtained. In the presence of iodine as catalyst, de-
oxygenative and regioselective 2-sulfonylation of quinoline
N-oxides with sodium sulfinate salts was developed by
Zhao’s group (Scheme 1c)8 and Yotphan’s group,9 providing
the desired products in moderate to high yield at room tem-
perature. Although various methods for the deoxygenative
sulfonylation of quinoline N-oxides have been established,
there are few examples providing a method for the direct
construction of 2-sulfonylquinolines via a radical pathway.
One example for the direct synthesis of 2-sulfonylquino-
lines via a Minisci-like radical sulfonylation of quinoline N-
oxides catalyzed by copper salts was reported by Han and
co-workers.10 In 2018, another example was presented by
W.-M. He’s group. In the absence of metal catalyst, the de-
oxygenative sulfonylation of quinoline N-oxides with sodi-
um sulfinates was realized via a dual radical coupling pro-
cess.11
DOI: 10.1055/s-0037-1611787; Art ID: ss-2019-f0092-op
Abstract An efficient and practical method for the synthesis of 2-sul-
fonylquinolines through copper-catalyzed deoxygenative C2-sulfonyla-
tion of quinoline N-oxides with 1,4-diazabicyclo[2.2.2]octane bis(sulfur
dioxide) (DABSO) and phenyldiazonium tetrafluoroborates is demon-
strated. Products with various substituents were obtained in moderate
to high yields.
Key words quinoline N-oxides, DABSO, radicals, sulfonylation, copper
2-Sulfonylquinolines play an important role in the
chemical and pharmaceutical community.1 Therefore, the
synthesis of 2-sulfonylquinolines has become a hot topic in
chemistry and has received more and more attention in re-
cent years. Traditionally, the methods for the preparation of
2-sulfonylquinolines are oxidation of the corresponding
sulfides2 or the coupling of sulfinate salts with 2-haloquin-
olines.3 However, some limitations of these protocols, such
as restricted substrate scope and non-commercial availabil-
ity of starting materials, limit the utility of these methods.
From the perspective of the abundance and accessibility of
quinoline N-oxides, the direct preparation of 2-sulfo-
nylquinolines from quinoline N-oxides would be more de-
sirable. In 2015, an H-phosphonate-mediated synthetic
strategy for the deoxygenative sulfonylation of heteroaro-
matic N-oxides using sulfonyl chlorides was reported by
Zhao’s group. Sulfonyl anions (nucleophile), generated from
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

B
G.-H. Li et al.
Paper
Synthesis
O
P
H
OiPr
, KOH
O
S
R1
OiPr
R1
O
(a)
R2
Cl
+
N
S
THF, RT, 1 h
R2
N
O
O
O
O
R1
NaI, TBHP
O
R1
R2
S
NHNH2
+
(b)
N
S
DMF/H2O (1:1), 100 °C
R2
N
O
O
S
O
O
S
I2 (0.2 equiv)
R1
R1
O
+
(c)
R2
ONa
N
CH3CN, RT, 2 h
N
R2
O
O
N2BF4
CuOTf (10 mol%)
CH2Cl2, 100 °C
O
DABSO
+
this work
+
N
N
S
R1
R2
R1
R2
O
O
Scheme 1 Synthesis of 2-sulfonylquinolines
Table 1 Optimization of the Reaction Conditionsa
Since the palladium-catalyzed aminosulfonylation of
aryl iodides using 1,4-diazabicyclo[2.2.2]octane bis(sulfur
dioxide) (DABSO) and hydrazines was reported by Willis
and co-workers in 2010,12 rapid progress has been made in
sulfonylation reactions using DABSO as the sulfonylation re-
agent.13 At present, alkynes,14 anilines,15 imidazopyri-
dines,16 N-arylacrylamides,17 and so on18 have been used as
good substrates to react with DABSO. Consistent with our
research interest in C–H bond activation and functionaliza-
tion of heterocyclic compounds,3f,19 herein we describe a
new protocol to access 2-sulfonylquinolines by the deoxy-
genative C2-sulfonylation of quinoline N-oxides with DAB-
SO via a radical mechanism.
At the beginning of our studies, a model reaction of
quinoline 1-oxide (1a), DABSO, and phenyldiazonium tetra-
fluoroborate (2a) was chosen to optimize the reaction con-
ditions (Table 1). Firstly, the effect of copper catalyst on the
reaction was examined. It was pleasing to find that the re-
action does indeed proceed, and afforded the desired 2-sul-
fonylquinoline 3a in 28% yield (entry 1) in the presence of
CuI as catalyst. An improved 50% yield of the desired prod-
uct was obtained when Cu(OAc)2 was used (entry 2). Other
copper catalysts, such as Cu(acac)2, Cu(OTf)2, Cu, and
Cu(NO3)2, could also catalyze the reaction, but the yields of
these reactions were not higher (entries 3–6). When CuOTf
was employed in this reaction, the highest yield (88%) of
product 3a was obtained (entry 7). Subsequently, a number
of solvents were examined with the aim of improving the
yield. When the reaction was conducted in DCE or acetone,
a low to moderate yield of 3a was isolated (entries 8 and 9).
DMF and DMSO were not effective for this transformation
(entries 10 and 11). A lower yield (57%) was obtained when
the reaction temperature was decreased from 100 °C to
80 °C (entry 12). However, there was no improvement in
N2BF4
conditions
+
DABSO +
O
S
N
O
N
1a
O
2a
3a
Entry
Catalyst
Solvent
Temp (°C)
Yield (%)b
1
2
CuI
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
100
100
100
100
100
100
100
100
100
100
100
80
28
Cu(OAc)2
Cu(acac)2
Cu(OTf)2
Cu
50
3
49
4
22
5
17
6
Cu(NO3)2
CuOTf
CuOTf
CuOTf
CuOTf
CuOTf
CuOTf
CuOTf
–
20
7
88
8
60
9
acetone
DMSO
DMF
28
10
11
12
13
14
15d
trace
trace
57
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
120
100
100
87
NRc
62
CuOTf
a Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), DABSO (0.4 mmol),
catalyst (10 mol%), solvent (1.5 mL), under N2.
b Isolated yields.
c NR = no reaction.
d Under air.
the yield when the reaction was conducted at a higher tem-
perature (120 °C, entry 13). The copper catalyst plays an
important role in this reaction, as no reaction occurred in
the absence of the catalyst (entry 14). The yield of 3a de-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

C
G.-H. Li et al.
Paper
Synthesis
creased obviously when the reaction was conducted under
air (entry 15), indicating that nitrogen gas protection is im-
portant for this reaction.
ed to the system, whereupon the reaction was completely
inhibited (Scheme 2a), which suggests that free-radical in-
termediates are involved in the reaction. When quinoline
was subjected to this reaction, no product was isolated
(Scheme 2b). This result indicated that quinoline N-oxide is
important for this reaction.
Based on the initial mechanistic studies and previous
reports,4–6,13,14,20 a possible pathway is described for this
sulfonylation reaction, as shown in Scheme 3. First, sulfonyl
radical intermediate B is generated from the reaction of
DABSO and aryldiazonium tetrafluoroborate. At the same
time, tertiary amine radical cation D, which can oxidize
[CuI] to [CuII], is formed. Then, reaction between B and in-
termediate A, which is generated from the reaction be-
tween quinoline N-oxide (1a) and [CuII], occurs to afford in-
termediate C. Finally, the desired product 3a is obtained
from intermediate C by deoxygenative elimination. Mean-
while, Cu(I) is regenerated for the next cycle. A Minisci-like
reaction mechanism, which would include a hydroxylamine
intermediate, has not been excluded.10
Next, the generality of this sulfonylation reaction was
investigated, under the optimal reaction conditions, with
respect to both quinoline N-oxides and aryldiazonium
tetrafluoroborates (Figure 1). To our delight, quinoline N-
oxides with an electron-donating (3a, 3b, 3g) or electron-
withdrawing group (3c, 3d, 3f) were compatible with these
reaction conditions, and the desired products were ob-
tained in moderate to good yields. No obvious substitution
effect was observed. Substituted aryldiazonium tetrafluo-
roborates bearing various synthetically useful functional
groups, such as CH3, F, Cl, Br, and OCH3 at the 2-, 3-, or 4-
position of the benzene ring, were well tolerated; the corre-
sponding products 3i–r were obtained in moderate to high
yields. Groups such as Br and Cl render the product ready
for further modifications. We were pleased to find that the
base-labile ester group (3h, 3o) was well tolerated under
the reaction system. It is worth noting that the CF3-substi-
tuted aryldiazonium tetrafluoroborate also displayed good
reactivity, to afford the corresponding product 3n in 73%
yield.
In conclusion, we have described an efficient copper-
catalyzed deoxygenative C2-sulfonylation reaction of quin-
oline N-oxides for the preparation of 2-sulfonylquinolines.
The resulting products with various functional groups were
readily obtained in moderate to high yields. Mechanism
To clarify the mechanism of this process, radical-trap-
ping reagents, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEM-
PO) and 2,6-di-tert-butyl-4-methylphenol (BHT), were add-
Cl
O
S
O
O
N
N
S
N
S
O
O
O
3a, 88%
3b, 80%
3c, 83%
F
Br
O
S
O
O
O
N
S
N
N
S
O
O
O
3d, 60%
3e, 68%
3f, 65%
O
O
O
S
O
S
O
N
N
N
S
O
O
O
3g, 66%
3h, 74%
3i, 86%
Cl
F
Br
O
S
O
S
O
S
N
N
N
O
O
O
3j, 72%
3k, 67%
3l, 73%
O
CF3
CO2CH3
O
S
O
S
O
S
N
N
N
O
O
O
3m, 82%
3n, 73%
3o, 81%
O
S
O
S
O
S
N
N
N
O
O
O
3p, 79%
3q, 78%
3r, 75%
Figure 1 Reaction scope. Reagents and conditions: quinoline N-oxide (0.2 mmol), aryldiazonium tetrafluoroborate (0.4 mmol), DABSO (0.4 mmol),
CuOTf (10 mol%), CH2Cl2 (1.5 mL), under N2, 100 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

D
G.-H. Li et al.
Paper
Synthesis
N2BF4
CuOTf (10 mol%)
O
S
(a)
DABSO
+
+
CH2Cl2, 100 °C, 24 h, N2
N
N
O
O
TEMPO (2.0 equiv)
BHT (2.0 equiv)
2a
3a n.d.
3a n.d.
1a
N2BF4
CuOTf (10 mol%)
O
S
(b)
+
DABSO
+
CH2Cl2, 100 °C, 24 h, N2
N
N
O
3a n.d.
2a
Scheme 2 Mechanism research (n.d.= not detected)
DABSO
+
Ph N2BF4
tion mixture. Then, the mixture was extracted with CH2Cl2
(3 × 50 mL) and the organic extracts were dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The crude
product was purified by column chromatography on silica gel to ob-
tain the pure quinoline N-oxide (70–90% yield).
DABCO
O
[Cul]
N
S
3a
Ph
O
N
R
R
R
[CuII]
N2
D
2-(Arylsulfonyl)quinolines 3; General Procedure
O
O
A sealable reaction tube equipped with a magnetic stirrer bar was
charged with a quinoline N-oxide (0.2 mmol), DABSO (0.4 mmol), an
aryldiazonium tetrafluoroborate (0.4 mmol), CuOTf (10 mol%), and
CH2Cl2 (1.5 mL). The reaction was carried out at 100 °C, under N2. Af-
ter completion, the mixture was diluted with EtOAc and washed with
water. After the solvent was removed under reduced pressure, the
residue was purified by column chromatography on silica gel to afford
the corresponding 2-(arylsulfonyl)quinoline 3.
S
Ph
B
O
S
N
O
[CuIII
]
Ph
C
O
N
O
[CuII]
[CuII]
A
N
SO2
O2S
N
DABSO =
2-(Phenylsulfonyl)quinoline (3a)8
N
1a
O
White solid; yield: 47 mg (88%); mp 159–161 °C.
Scheme 3 Possible reaction pathway
1H NMR (500 MHz, CDCl3):  = 8.30 (d, J = 8.5 Hz, 1 H), 8.14 (d, J = 8.5
Hz, 1 H), 8.11–8.05 (m, 3 H), 7.80 (d, J = 8.2 Hz, 1 H), 7.71 (ddd, J = 8.4,
6.9, 1.3 Hz, 1 H), 7.61–7.55 (m, 1 H), 7.55–7.50 (m, 1 H), 7.49–7.43 (m,
2 H).
studies indicated that free-radical intermediates are in-
volved in the reaction. Further work toward expanding this
protocol and further applications are underway in our labo-
ratory.
13C NMR (126 MHz, CDCl3):  = 158.11, 147.48, 139.16, 138.78,
133.76, 131.03, 130.43, 129.25, 129.11, 129.06, 128.87, 127.74,
117.75.
6-Methyl-2-(phenylsulfonyl)quinoline (3b)8
White solid; yield: 45 mg (80%); mp 152–154 °C.
1H NMR (500 MHz, CDCl3):  = 8.19 (d, J = 8.5 Hz, 1 H), 8.08 (dd, J =
14.7, 8.1 Hz, 3 H), 7.99 (d, J = 8.6 Hz, 1 H), 7.53 (dd, J = 13.9, 8.3 Hz, 3
H), 7.46 (t, J = 7.6 Hz, 2 H), 2.48 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 157.17, 146.15, 139.74, 139.38,
137.84, 133.63, 133.42, 130.07, 129.07, 128.99, 126.44, 117.84, 21.83.
NMR spectra were recorded on BRUKER AVANCE III HD 500MHz spec-
trometers, operating at 500 MHz for 1H NMR and at 126 MHz for 13
C
NMR acquisitions. 1H NMR chemical shifts () are given in ppm rela-
tive to TMS ( = 0.0); chemical shifts for 13C NMR spectra are reported
in ppm from TMS with the solvent as the internal standard. Data are
reported as follows: chemical shift, multiplicity (standard abbrevia-
tions), coupling constant(s), integration. HRMS spectra were per-
formed on Orbitrap Fusion Lumos. All major chemicals and solvents
were obtained from commercial sources and used without further
purification.
6-Chloro-2-(phenylsulfonyl)quinoline (3c)8
White solid; yield: 50 mg (83%); mp 169–171 °C.
1H NMR (500 MHz, CDCl3):  = 8.23 (d, J = 8.6 Hz, 1 H), 8.16 (d, J = 8.6
Hz, 1 H), 8.10–8.01 (m, 3 H), 7.80 (d, J = 2.2 Hz, 1 H), 7.65 (dd, J = 9.1,
2.2 Hz, 1 H), 7.55 (t, J = 7.4 Hz, 1 H), 7.48 (t, J = 7.7 Hz, 2 H).
Substituted Quinoline N-Oxides; General Procedure21
13C NMR (126 MHz, CDCl3):  = 158.45, 145.82, 138.86, 137.82,
135.38, 133.91, 132.14, 131.95, 129.40, 129.17, 129.13, 126.37,
118.68.
To a solution of the corresponding quinoline substrate (5 mmol) in
CH2Cl2 (30 mL), m-CPBA (7.5 mmol, 1.5 equiv) was added at 0 °C. The
reaction mixture was allowed to stir at room temperature for 24 h.
Next, saturated aq NaHCO3 solution (100 mL) was added to the reac-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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G.-H. Li et al.
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Synthesis
3-Bromo-2-(phenylsulfonyl)quinoline (3d)8
13C NMR (126 MHz, CDCl3):  = 158.25, 147.21, 139.16, 138.64,
137.17, 133.94, 132.49, 130.99, 130.67, 130.44, 129.21, 128.93,
127.75, 126.43, 117.78, 20.75.
White solid; yield: 42 mg (60%); mp 150–152 °C.
1H NMR (500 MHz, CDCl3):  = 8.47 (s, 1 H), 8.03 (d, J = 7.6 Hz, 2 H),
7.88 (d, J = 8.5 Hz, 1 H), 7.75–7.67 (m, 2 H), 7.61 (q, J = 7.9 Hz, 2 H),
7.51 (t, J = 7.7 Hz, 2 H).
2-((4-Fluorophenyl)sulfonyl)quinoline (3j)11a,22
White solid; yield: 41 mg (72%); mp 124–126 °C.
13C NMR (126 MHz, CDCl3):  = 154.44, 144.46, 142.96, 138.00,
133.89, 131.12, 130.29, 130.12, 129.84, 128.72, 126.54, 111.39.
1H NMR (500 MHz, CDCl3):  = 8.33 (d, J = 8.5 Hz, 1 H), 8.18–8.06 (m, 4
H), 7.82 (d, J = 8.2 Hz, 1 H), 7.77–7.69 (m, 1 H), 7.60 (t, J = 7.5 Hz, 1 H),
7.15 (t, J = 8.6 Hz, 2 H).
13C NMR (126 MHz, CDCl3):  = 167.00, 164.96, 158.02, 147.46,
138.86, 135.02, 132.03 (d, J = 9.7 Hz), 131.13, 130.37, 129.33, 128.89,
127.76, 117.49, 116.53, 116.35.
6-Methoxy-2-(phenylsulfonyl)quinoline (3e)8
White solid; yield: 41 mg (68%); mp 143–145 °C.
1H NMR (500 MHz, CDCl3):  = 8.15 (d, J = 8.6 Hz, 1 H), 8.07 (dd, J =
13.2, 8.0 Hz, 3 H), 7.98 (d, J = 9.3 Hz, 1 H), 7.51 (t, J = 7.4 Hz, 1 H), 7.45
(t, J = 7.6 Hz, 2 H), 7.34 (dd, J = 9.3, 2.7 Hz, 1 H), 7.01 (d, J = 2.7 Hz, 1 H),
3.86 (s, 3 H).
2-((4-Chlorophenyl)sulfonyl)quinoline (3k)8
White solid; yield: 41 mg (67%); mp 189–191 °C.
13C NMR (126 MHz, CDCl3):  = 159.89, 155.45, 143.69, 139.56,
136.86, 133.56, 131.86, 130.47, 129.06, 128.89, 124.36, 118.32,
104.62, 55.76.
1H NMR (500 MHz, CDCl3):  = 8.32 (d, J = 8.5 Hz, 1 H), 8.14 (d, J = 8.5
Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 8.01 (d, J = 8.6 Hz, 2 H), 7.82 (d, J = 8.2
Hz, 1 H), 7.73 (t, J = 7.5 Hz, 1 H), 7.60 (t, J = 7.5 Hz, 1 H), 7.44 (d, J = 8.6
Hz, 2 H).
13C NMR (126 MHz, CDCl3):  = 157.82, 147.48, 140.60, 138.89,
137.53, 131.17, 130.61, 130.38, 129.44, 129.39, 128.92, 127.77,
117.52.
6-Fluoro-2-(phenylsulfonyl)quinoline (3f)22
White solid; yield: 37 mg (65%); mp 119–121 °C.
1H NMR (500 MHz, CDCl3):  = 8.26 (d, J = 8.6 Hz, 1 H), 8.16 (d, J = 8.6
Hz, 1 H), 8.11 (dd, J = 9.3, 5.3 Hz, 1 H), 8.09–8.03 (m, 2 H), 7.55 (t, J =
7.4 Hz, 1 H), 7.52–7.45 (m, 3 H), 7.42 (dd, J = 8.5, 2.7 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 162.98, 160.97, 157.70, 144.56,
139.01, 138.06 (d, J = 5.8 Hz), 133.84, 133.18 (d, J = 9.6 Hz), 129.83 (d,
J = 10.6 Hz), 129.15, 129.08, 121.69 (d, J = 26.2 Hz), 118.55, 110.8 (d,
J = 22.2 Hz).
2-((4-Bromophenyl)sulfonyl)quinoline (3l)11a,22
White solid; yield: 51 mg (73%); mp 145–147 °C.
1H NMR (500 MHz, CDCl3):  = 8.32 (d, J = 8.5 Hz, 1 H), 8.13 (d, J = 8.5
Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 7.93 (d, J = 8.5 Hz, 2 H), 7.82 (d, J = 8.2
Hz, 1 H), 7.73 (dd, J = 11.4, 4.0 Hz, 1 H), 7.65–7.57 (m, 3 H).
3-Methyl-2-(phenylsulfonyl)quinoline (3g)6
13C NMR (126 MHz, CDCl3):  = 157.77, 147.49, 138.90, 138.08,
132.42, 131.18, 130.66, 130.38, 129.40, 129.25, 128.92, 127.77,
117.52.
White solid; yield: 37 mg (66%); mp 150–152 °C.
1H NMR (500 MHz, CDCl3):  = 8.05–7.94 (m, 3 H), 7.81 (d, J = 8.4 Hz, 1
H), 7.69 (d, J = 8.0 Hz, 1 H), 7.63–7.54 (m, 2 H), 7.54–7.46 (m, 3 H),
2.81 (s, 3 H).
2-((4-Methoxyphenyl)sulfonyl)quinoline (3m)11a,22
White solid; yield: 49 mg (82%); mp 130–132 °C.
13C NMR (126 MHz, CDCl3):  = 156.94, 144.67, 139.89, 138.79,
133.56, 129.97, 129.80, 129.50, 129.16, 129.04, 128.67, 128.59,
126.72, 18.81.
1H NMR (500 MHz, CDCl3):  = 8.29 (d, J = 8.3 Hz, 1 H), 8.11 (dd, J =
11.6, 4.7 Hz, 2 H), 8.00 (dd, J = 8.7, 1.5 Hz, 2 H), 7.79 (d, J = 8.1 Hz, 1 H),
7.71 (t, J = 7.7 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 6.92 (dd, J = 8.7, 1.4 Hz,
2 H), 3.77 (d, J = 1.5 Hz, 3 H).
13C NMR (126 MHz, CDCl3):  = 163.91, 158.68, 147.46, 138.68,
131.32, 130.92, 130.52, 130.41, 129.07, 128.78, 127.70, 117.57,
114.41, 55.67.
Methyl 2-(Phenylsulfonyl)quinoline-6-carboxylate (3h)
White solid; yield: 48 mg (74%); mp 146–148 °C.
1H NMR (500 MHz, CDCl3):  = 8.63 (s, 1 H), 8.50 (d, J = 8.5 Hz, 1 H),
8.36 (d, J = 8.9 Hz, 1 H), 8.28 (d, J = 8.5 Hz, 1 H), 8.20 (d, J = 8.9 Hz, 1 H),
8.16 (d, J = 7.9 Hz, 2 H), 7.64 (t, J = 7.3 Hz, 1 H), 7.56 (t, J = 7.6 Hz, 2 H),
4.00 (s, 3 H).
2-((4-(Trifluoromethyl)phenyl)sulfonyl)quinoline (3n)11a,22
White solid; yield: 49 mg (73%); mp 126–128 °C.
13C NMR (126 MHz, CDCl3):  = 165.98, 160.22, 149.14, 140.21,
138.63, 134.01, 130.73, 130.64, 130.49, 130.39, 129.27, 129.19,
128.04, 118.38, 52.73.
HRMS (ESI): m/z [M + H]+ calcd for C17H13NO4S: 328.06467; found:
328.06381.
1H NMR (500 MHz, CDCl3):  = 8.35 (d, J = 8.5 Hz, 1 H), 8.22 (d, J = 8.2
Hz, 2 H), 8.17 (d, J = 8.5 Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 7.83 (d, J = 8.2
Hz, 1 H), 7.74 (t, J = 6.7 Hz, 3 H), 7.62 (t, J = 7.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 157.38, 147.52, 142.66, 139.00,
135.47, 135.20, 131.28, 130.39, 129.75, 129.56, 129.00, 127.80,
126.21, 126.19, 126.16, 126.13, 124.26, 122.09, 117.59.
2-(o-Tolylsulfonyl)quinoline (3i)11a,22
White solid; yield: 49 mg (86%); mp 115–117 °C.
Methyl 4-(Quinolin-2-ylsulfonyl)benzoate (3o)
1H NMR (500 MHz, CDCl3):  = 8.31 (d, J = 8.5 Hz, 1 H), 8.23 (d, J = 7.9
Hz, 1 H), 8.10 (d, J = 8.5 Hz, 1 H), 8.04 (d, J = 8.6 Hz, 1 H), 7.81 (d, J = 8.2
Hz, 1 H), 7.73–7.66 (m, 1 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.43 (t, J = 7.5 Hz,
1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 1 H), 2.49 (s, 3 H).
White solid; yield: 53 mg (81%); mp 130–132 °C.
1H NMR (500 MHz, CDCl3):  = 8.34 (d, J = 8.5 Hz, 1 H), 8.20–8.10 (m, 5
H), 8.07 (d, J = 8.6 Hz, 1 H), 7.82 (d, J = 8.2 Hz, 1 H), 7.73 (t, J = 7.7 Hz, 1
H), 7.61 (t, J = 7.5 Hz, 1 H), 3.87 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

F
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13C NMR (126 MHz, CDCl3):  = 165.60, 157.58, 147.50, 142.98,
138.92, 134.75, 131.20, 130.41, 130.18, 129.46, 129.21, 128.96,
127.77, 117.66, 52.70.
HRMS (ESI): m/z [M + H]+ calcd for C17H13NO4S: 328.06451; found:
328.06381.
M.; Pannecouque, C.; De Clercq, E.; Balzarini, J. Antimicrob.
Agents Chemother. 2003, 47, 2951. (f) Sun, P.; Yang, D.; Wei, W.;
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D.; Yue, H.; He, C.; Zhang, Y.; Wang, H. Green Chem. 2017, 19,
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X.; Wei, W. Chin. J. Org. Chem. 2015, 35, 1848.
2-(m-Tolylsulfonyl)quinoline (3p)
White solid; yield: 45 mg (79%); mp 125–127 °C.
1H NMR (500 MHz, CDCl3):  = 8.31 (d, J = 8.5 Hz, 1 H), 8.13 (t, J = 9.0
Hz, 2 H), 7.87 (d, J = 7.7 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 1 H), 7.72 (t, J = 7.7
Hz, 1 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.38–7.31 (m, 2 H), 2.35 (s, 3 H).
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13C NMR (126 MHz, CDCl3):  = 158.23, 147.51, 139.38, 139.02,
138.72, 134.58, 130.98, 130.49, 129.28, 129.20, 128.99, 128.87,
127.71, 126.22, 117.84, 21.34.
HRMS (ESI): m/z [M + H]+ calcd for C16H13NO2S: 284.07465; found:
284.07398.
2-Tosylquinoline (3q)8
White solid; yield: 44 mg (78%); mp 142–144 °C.
1H NMR (500 MHz, CDCl3):  = 8.29 (d, J = 8.5 Hz, 1 H), 8.11 (dd, J =
11.1, 8.7 Hz, 2 H), 7.95 (d, J = 8.3 Hz, 2 H), 7.80 (d, J = 8.1 Hz, 1 H),
7.74–7.66 (m, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.25 (d, J = 8.1 Hz, 2 H),
2.33 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 158.41, 147.48, 144.82, 138.69,
136.17, 130.95, 130.45, 129.79, 129.14, 129.10, 128.82, 127.70,
117.70, 21.67.
3-Methyl-2-tosylquinoline (3r)7,11a
White solid; yield: 45 mg (75%); mp 114–116 °C.
1H NMR (500 MHz, CDCl3):  = 7.99 (s, 1 H), 7.86 (t, J = 9.6 Hz, 3 H),
7.70 (d, J = 8.0 Hz, 1 H), 7.58 (dd, J = 11.2, 4.0 Hz, 1 H), 7.52 (t, J = 7.4
Hz, 1 H), 7.30 (d, J = 8.1 Hz, 2 H), 2.80 (s, 3 H), 2.40 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 157.14, 144.73, 144.51, 139.83,
135.84, 130.03, 129.72, 129.51, 129.37, 129.16, 128.96, 128.62,
126.68, 21.74, 18.90.
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Chem. 2016, 81, 4981.
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Funding Information
(10) Du, B.; Qian, P.; Wang, Y.; Mei, H.; Han, J.; Pan, Y. Org. Lett. 2016,
18, 4144.
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W.-F.; Cao, Z.; He, W.-M. Org. Chem. Front. 2018, 5, 2604. (b) Xie,
L.-Y.; Peng, S.; Jiang, L.-L.; Peng, X.; Xia, W.; Yu, X.; Wang, X.-X.;
Cao, Z.; He, W.-M. Org. Chem. Front. 2019, 6, 167.
We gratefully acknowledge the financial support from the National
Natural Science Foundation of China (21402103, 21772107), the Chi-
na Postdoctoral Science Foundation (150030), and the Research Fund
of Qingdao Agricultural University’s Highlevel Person (631303).
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Supporting Information
(13) For selected examples, see: (a) Qiu, G.-Y.-S.; Lai, L.-F.; Cheng, J.;
Wu, J. Chem. Commun. 2018, 54, 10405. (b) Mao, R.-Y.; Zheng,
D.-Q.; Xia, H.-G.; Wu, J. Org. Chem. Front. 2016, 3, 693. (c) Wang,
H.-P.; Sun, S.; Cheng, J. Org. Lett. 2017, 19, 5844. (d) Vedovato,
V.; Talbot, E. P. A.; Willis, M. C. Org. Lett. 2018, 20, 5493. (e) Bao,
W.-H.; Wu, C.; Wang, J.-T.; Xia, W.; Chen, P.; Tang, Z.; Xu, X.; He,
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(h) Tribby, A. L.; Rodríguez, I.; Shariffudin, S.; Ball, N. D. J. Org.
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611787.
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