Visible-light-induced aerobic C3-H fluoroalkoxylation of quinoxalin-2(1: H)-ones with fluoroalkyl alcohols

Article abstract of DOI:10.1039/c9ra10194b

A novel and efficient method of visible-light-induced C3-H fluoroalkoxylation of quinoxalin-2(1H)-ones with fluoroalkyl alcohols is developed. This approach uses readily available fluoroalkyl alcohols as fluoroalkoxylation reagents and displays a wide substrate scope, providing the fluoroalkoxylated products in moderate to good yields. Compared with the previous method, such a transformation uses oxygen as an oxidant, which avoids the utilization of plenty of PhI(TFA)₂. In addition, this strategy also gives a practical tool for the rapid synthesis of histamine-4 receptor antagonist and new N-containing bidentate ligands. A radical mechanism was suggested according to the results of control experiments.

Full text of DOI:10.1039/c9ra10194b

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Visible-light-induced aerobic C3–H
fluoroalkoxylation of quinoxalin-2(1H)-ones with
fluoroalkyl alcohols†
Cite this: RSC Adv., 2020, 10, 2016
a
Xiaobo Xu,ab Chengcai Xia,
Xiaojun Li,c Jian Suna and Liqiang Haoa
*
A novel and efficient method of visible-light-induced C3–H fluoroalkoxylation of quinoxalin-2(1H)-ones
with fluoroalkyl alcohols is developed. This approach uses readily available fluoroalkyl alcohols as
fluoroalkoxylation reagents and displays a wide substrate scope, providing the fluoroalkoxylated products
in moderate to good yields. Compared with the previous method, such a transformation uses oxygen as
an oxidant, which avoids the utilization of plenty of PhI(TFA)2. In addition, this strategy also gives
a practical tool for the rapid synthesis of histamine-4 receptor antagonist and new N-containing
bidentate ligands. A radical mechanism was suggested according to the results of control experiments.
Received 5th December 2019
Accepted 5th January 2020
DOI: 10.1039/c9ra10194b
rsc.li/rsc-advances
metal residues in nal products are quite difficult to remove,
which is a crucial issue in the pharmaceutical industry.4
Introduction
As an important class of heterocyclic units, quinoxalin-2(1H)-
ones widely exist in natural products, organic intermediates
and pharmaceuticals.5 Therefore, great efforts have been
devoted to the development of new methods for the synthesis of
quinoxalin-2(1H)-ones and its derivatives.6 Thanks to the
development of C–H functionalization, lots of transformations
so far have been achieved,7 such as phosphorization,8 amina-
As a class of uorine-containing molecules, uoroalkoxyl aryl
ethers are widely used in agricultural agents, advanced mate-
rials and pharmaceuticals because of the unique impact of the
uorine atoms on physicochemical and biological properties.1
The conventional methods to prepare such compounds are
nucleophilic aromatic substitution reactions (SNAr), which
usually suffer from high temperature and low reactivity.2
Consequently, the development of more practical and efficient
approaches to access uoroalkoxyl aryl ethers has recently
received considerable attention.
In recent years, transition-metal-catalyzed reactions have
been regarded as reliable strategies for the preparation of u-
oroalkoxyl aryl ethers.3 For example, Weng,3a,b Ji,3c Crousse,3d
and Qing3e reported novel methods for the construction of u-
oroalkoxyl aryl ethers through copper-catalyzed C–O cross
couplings of aryl halides or aryl boronic acids with uoroalkyl
alcohols. In addition, the Singh group achieved a palladium-
catalyzed dehalogenated coupling of aryl halides with uo-
roalkyl alcohols for the synthesis of uoroalkoxyl aryl ethers.3f
Alternatively, palladium-catalyzed amide-directed C–H tri-
uoroethoxylation provided another route to uoroalkoxyl aryl
ethers.3g Despite the utilities, the pre-functionalization of the
starting materials in above methods limited their applications.
In addition, the metal catalysts are toxic, and trace amounts of
tion,9
alkylation,10
arylation,11
acylation,12
tri-
uoromethylation,13 diuoromethylation,14 alkoxylation15 and
thiolation.16 In sharp contrast, C–H uoroalkoxylation of qui-
noxalin-2(1H)-ones was rarely reported. Very recently, the rst
example of C3–H uoroalkoxylation of quinoxalin-2(1H)-ones
with uoroalkyl alcohols was reported by Li and Zhang (Scheme
1a).17 However, such reaction suffers from plenty of PhI(TFA)2,
which failed to meet the requirements of green chemistry.18
As a clean and sustainable approach, photocatalyzed C–H
functionalization has become an important strategy to intro-
duce uorine-containing functional groups into organic mole-
cules.19 For a long time, we are always working to develop
aPharmacy College, Shandong First Medical University, Shandong Academy of Medical
Sciences, Taian 271000, China. E-mail: xiachc@163.com
bShanghai Synmedia Chemical Co., Ltd, Shanghai 201201, China
cDepartment of Fundamental Medicine, Xinyu University, Xinyu 338004, China
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and analytical data. CCDC 1958968. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c9ra10194b
Scheme 1 The C3–H fluoroalkoxylation of quinoxalin-2(1H)-ones.
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Table 1 Optimization of reaction conditionsa,b
photocatalyzed C–H functionalization of N-heterocycle.20
Recently, our group reported photocatalyzed aerobic C3–H
peruoroalkylation of quinoxalin-2(1H)-ones with sodium per-
uoroalkanesulnates.13a As
a further work, herein, we
demonstrated a visible light induced aerobic C3–H uo-
roalkoxylation of quinoxalin-2(1H)-ones with uoroalkyl alco-
hols, providing a green and efficient method to introduce
uoroalkoxy into quinoxalin-2(1H)-ones molecules (Scheme
1b). During the preparation of our manuscript, Wang and Li
groups developed an useful approach for alkoxylation of qui-
noxalin-2(1H)-ones respectively, but it only gave one tri-
uoroethoxylated example.15a,b Therefore, the development of
simple and widely applicable approaches for the C3–H uo-
roalkoxylation of quinoxalin-2(1H)-ones is still meaningful. In
addition, many further transformations have been done in our
work, which clearly demonstrated the application value of the
reaction.
Entry
Photocatalyst
Additive
Solvent
Yieldb [%]
1
2
3
4
5
6
7
8
Rose bengal
Acr+–Mes ClO4
Fluorescein
Eosin Y
Methylene blue
Erythrosine
Ru(bpy)3Cl2
Ir(ppy)3
—
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
CH3CN
DCE
DMF
H2O
—
—
—
—
—
25
65
ꢀ
Trace
70
Trace
Trace
28
Trace
0
66
43
20
34
48
52
Trace
24
Trace
85
0
15
27
0
9
—
10
11
12
13
14
15c
16c
17c
18c
19d
20e
21d,f
22d,g
23d,h
TFA
H3PO4
Na2CO3
AcONa
Bu4NBr
—
—
—
—
—
Results and discussion
Initially, the coupling reaction of quinoxalin-2(1H)-ones with
triuoroethanol was performed in air by using 5 mol% of rose
bengal as a photocatalyst under the radiation of 18 W blue LED.
The desired product (2) was obtained in 25% yield (Table 1,
entry 1). Encouraged by this result, we next screened a series of
photocatalysts such as Acr+–Mes ClO4ꢀ, uorescein, eosin Y,
methylene blue, erythrosine, Ru(bpy)3Cl2 and Ir(ppy)3. It was
found that eosin Y was the best photocatalyst, which provided
the product in 70% yield (Table 1, entries 2–8). No desired
product (2) was generated without photocatalyst (Table 1, entry
9). To further improve the product yield, some additives and
solvents were explored, but no better result was gained (Table 1,
entries 10–18). To our delight, the yield was enhanced to 85%
when the reaction was performed under O2 atmosphere (Table
1, entry 19). No desired product was generated when the
transformation was carried out under N2 atmosphere (Table 1,
entry 20). These results implied that O2 played a key role in this
transformation. Further investigations on the light sources
revealed that blue light was the best choice for the reaction
(Table 1, entries 21–23).
—
—
—
—
a
Reaction conditions: 1a (0.2 mmol), photocatalyst (5 mol%), additive
(1.5 equiv.), CF3CH2OH (0.5 mL), blue LED (18 W), rt, under air
atmosphere, 24 h. Isolated yields. CF3CH2OH (5.0 equiv.), solvent
(0.5 mL). Under O2 atmosphere. Under N2 atmosphere. Green
LED (18 W). g White LED (18 W). h Without light.
b
c
d
e
f
the corresponding products (28 and 29) in 75% and 78% yields,
responsively.
Aer that, the efforts were further focused on the exploration
of uoroalkyl alcohols (Table 3). It was found that uoroalkyl
alcohols such as pentauoro-1-propanol, heptauoro-1-
Having established the best reaction conditions, we subse-
quently explored the substrate scope of quinoxalin-2(1H)-ones
(Table 2). Generally, the C–H uoroalkoxylation reaction
showed good substituent group tolerance. Quinoxalin-2(1H)-
ones bearing different of N-protecting groups such as methyl
(–CH3), ethyl (–C2H5), butyl (–nC4H9), isoamyl (–iC5H11), cyclo-
propylmethyl, cyclohexylmethyl and esteryl (–CH2CO2R) were
well tolerant, giving the corresponding products (2–9) in 70–
87% yields. The N-benzyl groups (–CH2Ar) also were compatible,
affording the target products in good yields (10–19). The
molecular structure of product 18 was conrmed by X-ray
diffraction studies (see ESI†). In addition, quinoxalin-2(1H)-
ones with substituents on the benzene ring also could undergo
butanol,
tetrauoro-1-propanol,
triuorobutan-1-butanol,
diuoro-1-ethanol and uoro-1-ethanol could also undergo
this reaction successfully, producing the corresponding prod-
ucts (30–41) in good yields. Regrettably, the longer-chain and
bulky uoroalkyl alcohols such as octauoropentyl alcohol,
hexauoroisopropanol and nonauoro-tert-butanol could not
be converted into corresponding products (42–44) since the
effect of large steric hindrance. We also tried to extend the
method to the modication of other important N-containing
molecules, but failed (see ESI, Scheme S1†).
To demonstrate the application value of the reaction, we
rstly performed a gram-scale reaction. To our delight, the
product (2) could be isolated in 72% yield (Scheme 2a). In
addition, the histamine-4 receptor antagonist 45 could be ob-
tained in 63% yield through the C–H triuoroethoxylation,
followed by nucleophilic substitution (Scheme 2b).21
this
transformation
smoothly,
providing
the
tri-
uoroethoxylated products (20–27) in 45–82% yields. Further-
more, quinoxalin-2(1H)-one and 2H-benzo[b][1,4]oxazin-2-one
were also tolerant under standard reaction conditions, yielding
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Table 2 Substrate scope of quinoxalin-2(1H)-onesa,b
Scheme 2 Gram-scale synthesis and the synthesis of histamine-4
receptor antagonist.
traditional C–N cross-couplings to examine its reactivity. It was
found that compare to other ligands that were reported in the
literature,22 the ligand 46 has relatively good reactivity,
providing the product in moderate yield.
To obtain more details of the C–H uoroalkoxylation reac-
tion, the mechanism investigations were started. Firstly, the
C–H uoroalkoxylation reaction was dramatically suppressed
when two equivalents of TEMPO (2,2,6,6-tetramethylpiper-
a
Reaction conditions: 1 (0.2 mmol), eosin Y (5 mol%), CF3CH2OH (0.5 idinooxy) or DPE (1,1-diphenylethlene) was added respectively
mL), blue LED (18 W), rt, O2, 24 h. b Isolated yields.
(Scheme 4). These results implied that a radical pathway might
be involved in this reaction. The visible light irradiation on/off
experiments revealed that the visible light played a crucial role
in this reaction (Fig. 1). In addition, the measurement result of
Table 3 Substrate scope of fluoroalkyl alcoholsa,b
potential indicated that the generation of triuoroethoxy
radical from triuoroethanol is very difficult (Scheme S2†).
Based on the results of mechanism studies and previous
works,7–17 we proposed a reasonable mechanism for this visible-
light-induced C–H uoroalkoxylation reaction (Scheme 5).
Initially, the excited eosin Y* was generated under the irradia-
tion of blue LEDs. A subsequent single-electron-transfer (SET)
process took place between eosin Y* and N-methyl-quinoxalin-
2(1H)-one 1a to form the eosin Ycꢀ species and intermediate A.
The intermediate A was further trapped by triuoroethanol to
generate intermediate B. Meanwhile, the second single-
electron-transfer (SET) process happened between eosin Ycꢀ
species and O2 to give O2cꢀ species and eosin Y. The nal
a
Reaction conditions: 1 (0.2 mmol), eosin Y (5 mol%), RfOH (0.5 mL),
blue LED (18 W), rt, O2, 24 h. b Isolated yields.
Furthermore, the N-containing bidentate ligand 46 also could
be synthesized in 50% yield by using product 28 as building
block (Scheme 3). We further applied this ligand to catalyse
Scheme 3 Further chemistry.
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functional groups were tolerant, providing the uoroalkoxy-
lated products in moderate to good yields. The control experi-
ments results demonstrated that a radical pathway was
answerable for this reaction.
Experimental section
General information
The starting materials, solvents and other chemicals used in
experiments were purchased from Energy Chemical without
further purication. All products were isolated by short chro-
matography on a silica gel (200–300 mesh) column using
Scheme 4 Mechanism studies.
1
petroleum ether (60–90 C) and ethyl acetate. H, 13C and 19F
ꢁ
NMR spectra were recorded on Bruker Avance DRX-500 spec-
trometers at ambient temperature with CDCl3 as solvent and
tetramethylsilane (TMS) as the internal standard. All chemical
shi values are quoted in ppm and coupling constants quoted
in Hz. Compounds for HRMS were analyzed by positive mode
electrospray ionization (ESI) using Agilent 6530 QTOF mass
spectrometer.
General procedure for the synthesis of uoroalkoxylated
quinoxalin-2(1H)-ones (2–41)
Quinoxalin-2(1H)-ones derivatives
1 (0.2 mmol), eosin Y
(5 mol%), RfOH (0.5 mL) were combined in a 15 mL tube. The
mixture was then stirred for 24 hours under O2 atmosphere by
the radiation of 18 W blue LED. Aer the conversion was
completed as indicated by TLC, to the residue was added water
(10 mL) and extracted with ethyl acetate (5 mL ꢂ 3). The
collected organic layer was washed with brine, dried with
MgSO4, ltered and concentrated in vacuo. The residue was
puried directly by ash column chromatography.
Fig. 1 Visible light irradiation on/off experiments.
General procedure for the gram-scale synthesis of
uoroalkoxylated quinoxalin-2(1H)-one (2)
Quinoxalin-2(1H)-ones derivatives 1a (10.0 mmol), eosin Y
(5 mol%), RfOH (20 mL) were combined in a 100 mL ask. The
mixture was then stirred for 24 hours under O2 atmosphere by
the radiation of 18 W blue LED. Aer the conversion was
completed as indicated by TLC, to the residue was added water
(10 mL) and extracted with ethyl acetate (50 mL ꢂ 3). The
collected organic layer was washed with brine, dried with
MgSO4, ltered and concentrated in vacuo. The residue was
puried directly by ash column chromatography.
Scheme 5 Plausible mechanism.
General procedure for the synthesis of histamine-4 receptor
antagonist (45)
product was obtained through oxidation and proton transfer
process with the release of H2O2, which was detected by a starch
potassium iodide test paper.
Quinoxalin-2(1H)-ones derivative 1y (0.5 mmol), eosin
Y
(5 mol%), RfOH (1.0 mL) were combined in a 15 mL tube. The
mixture was then stirred for 24 hours under O2 atmosphere by
the radiation of 18 W blue LED. Aer the conversion was
completed as indicated by TLC, to the residue was added water
Conclusions
We have reported a visible-light-induced aerobic C3–H uo- (10 mL) and extracted with ethyl acetate (10 mL ꢂ 3). The
roalkoxylation of quinoxalin-2(1H)-ones with uoroalkyl alco- collected organic layer was washed with brine, dried with
hols. This approach uses readily available uoroalkyl alcohols MgSO4, ltered and concentrated in vacuo. Aer the solvent was
as uoroalkoxylation reagents and substrates with various removed, DMSO (1.5 mL), Et3N (1.5 equiv.) and N-
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methylpiperazine (1.5 equiv.) were added to the residue, and the
mixture was stirred at 120 ꢁC for 12 hours. Aer the conversion
was completed as indicated by TLC, to the residue was added
water (10 mL) and extracted with ethyl acetate (10 mL ꢂ 3). The
collected organic layer was washed with brine, dried with
MgSO4, ltered and concentrated in vacuo. The residue was
puried directly by ash column chromatography.
1-Ethyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one (3)
White solid (82% yield), mp 126–127 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (dd, J ¼ 8.2, 1.5 Hz, 1H), 7.50–7.45 (m, 1H), 7.35–
7.30 (m, 2H), 4.90 (q, J ¼ 8.3 Hz, 2H), 4.36 (q, J ¼ 7.2 Hz, 2H),
1.40 (t, J ¼ 7.2 Hz, 3H). 13C NMR (126 MHz, CDCl3) d 152.03,
149.71, 130.99, 130.32, 128.16, 128.14, 124.03, 123.15 (q, J ¼
278.5 Hz), 113.67, 62.81 (q, J ¼ 37.8 Hz), 37.87, 12.36. 19F NMR
(471 MHz, CDCl3) d ꢀ73.00. HRMS (ESI): calculated for
+
C
12H11F3N2O2 : 273.0846 [M + H]+, found: 273.0849.
General procedure for the synthesis of 3,30-bis(2,2,2-
triuoroethoxy)-2,20-biquinoxaline (46)
1-Butyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one (4)
Fluoroalkoxylated quinoxalin-2(1H)-one 28 (2.0 mmol), POCl3
White solid (80% yield), mp 118–119 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (dd, J ¼ 7.9, 1.3 Hz, 1H), 7.50–7.44 (m, 1H), 7.31
(dd, J ¼ 13.1, 8.1 Hz, 2H), 4.89 (q, J ¼ 8.3 Hz, 2H), 4.33–4.26 (m,
2H), 1.79–1.72 (m, 2H), 1.49 (dd, J ¼ 15.1, 7.5 Hz, 2H), 1.00 (t, J ¼
7.4 Hz, 3H). 13C NMR (126 MHz, CDCl3) d 152.04, 149.94, 131.28,
130.29, 128.12, 128.05, 123.99, 123.15 (q, J ¼ 278.5 Hz), 113.84,
62.82 (q, J ¼ 37.8 Hz), 42.62, 29.25, 20.22, 13.76. 19F NMR (471
(1.2 equiv.) and pyridine (1.0 equiv.) were combined in a 15 mL
ꢁ
tube. The mixture was then stirred at 160 C for 30 min. Aer
the conversion was completed as indicated by TLC, to the
residue was added saturated NaHCO3 solution (15 mL) and
extracted with ethyl acetate (20 mL ꢂ 3). The collected organic
layer was washed with brine, dried with MgSO4, ltered and
concentrated in vacuo. Aer the solvent was removed, NiCl2-
$6H2O (5 mol%), LiCl (1.0 equiv.), zinc dust (1.2 equiv.) and
DMF (10.0 mL) in a 50 mL ask was heated to 50 ꢁC, then,
a grain of iodine crystal and two drops of acetic acid were added
to the mixture. The mixture was stirred at 60 ꢁC for 2 hours.
Aer the conversion was completed as indicated by TLC, to the
residue was added water (15 mL) and extracted with ethyl
acetate (20 mL ꢂ 3). The collected organic layer was washed
with brine, dried with MgSO4, ltered and concentrated in
vacuo. The residue was puried directly by ash column
chromatography.
MHz, CDCl3)
d
ꢀ73.01. HRMS (ESI): calculated for
+
C
14H15F3N2O2 : 301.1159 [M + H]+, found: 301.1154.
1-Isopentyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one (5)
White solid (87% yield), mp 123–124 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (d, J ¼ 7.8 Hz, 1H), 7.50–7.45 (m, 1H), 7.34–7.27
(m, 2H), 4.88 (q, J ¼ 8.3 Hz, 2H), 4.32–4.26 (m, 2H), 1.78 (dd, J ¼
13.3, 6.6 Hz, 1H), 1.67–1.62 (m, 2H), 1.04 (d, J ¼ 6.6 Hz, 6H). 13
C
NMR (126 MHz, CDCl3) d 152.01, 149.86, 131.22, 130.32, 128.13,
128.09, 124.00, 123.15 (q, J ¼ 278.5 Hz), 113.75, 62.83 (q, J ¼ 37.8
Hz), 41.44, 35.82, 26.44, 22.47. 19F NMR (471 MHz, CDCl3)
d ꢀ72.56. HRMS (ESI): calculated for C15H17F3N2O2+: 315.1315
[M + H]+, found: 315.1318.
General procedure for the synthesis of 1-(p-tolyl)-1H-indole
(49)
1-(Cyclopropylmethyl)-3-(2,2,2-triuoroethoxy)quinoxalin-
2(1H)-one (6)
K3PO4 (2.2 mmol) was added to a Schlenk tube equipped with
a stirring bar and the tube was dried under vacuum and then
lled with an argon. CuI (0.1 mmol) and ligand (0.1 mmol) and
DMF (4.0 mL) were added and the mixture was stirred at 50 ꢁC
for 1 h, 1-iodo-4-methylbenzene (2.0 mmol) and indole (3.0
White solid (81% yield), mp 136–137 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (dd, J ¼ 7.9, 1.0 Hz, 1H), 7.51–7.45 (m, 1H), 7.43 (d,
J ¼ 8.0 Hz, 1H), 7.33 (t, J ¼ 7.5 Hz, 1H), 4.90 (q, J ¼ 8.3 Hz, 2H),
4.23 (d, J ¼ 7.0 Hz, 2H), 1.31–1.25 (m, 1H), 0.62–0.53 (m, 4H).
13C NMR (126 MHz, CDCl3) d 152.18, 150.28, 131.50, 130.22,
128.09, 128.05, 124.02, 123.17 (q, J ¼ 278.5 Hz), 114.09, 62.86 (q,
J ¼ 37.8 Hz), 46.74, 9.57, 4.13. 19F NMR (471 MHz, CDCl3)
d ꢀ72.97. HRMS (ESI): calculated for C14H13F3N2O2+: 299.1002
[M + H]+, found: 299.1006.
ꢁ
mmol) were added, and then the mixture was stirred at 110 C
for 24 h. Aer the completion of the reaction, the mixture was
cooled, then the precipitate was removed by ltration and the
product was extracted with ethyl acetate (20 mL ꢂ 3). The
collected organic layer was washed with brine, dried with
MgSO4, ltered and concentrated in vacuo. The residue was
puried directly by ash column chromatography.
1-(Cyclohexylmethyl)-3-(2,2,2-triuoroethoxy)quinoxalin-
2(1H)-one (7)
1-Methyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one (2)
White solid (84% yield), mp 145–146 ꢁC. 1H NMR (500 MHz,
White solid (85% yield), mp 154–155 ꢁC. 1H NMR (500 MHz, CDCl3) d 7.57 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.40–7.36 (m, 1H), 7.26–
CDCl3) d 7.65 (dd, J ¼ 8.0, 1.3 Hz, 1H), 7.51–7.45 (m, 1H), 7.36– 7.20 (m, 2H), 4.81 (q, J ¼ 8.3 Hz, 2H), 4.10 (d, J ¼ 7.3 Hz, 2H),
7.32 (m, 1H), 7.30 (d, J ¼ 8.3 Hz, 1H), 4.90 (q, J ¼ 8.3 Hz, 2H), 1.88–1.80 (m, 1H), 1.68–1.56 (m, 5H), 1.12 (t, J ¼ 9.9 Hz, 5H). 13
C
3.74 (s, 3H). 13C NMR (126 MHz, CDCl3) d 151.03, 149.21, NMR (126 MHz, CDCl3) d 151.05, 149.37, 130.67, 129.20, 127.07,
131.10, 128.96, 127.14, 126.86, 123.21, 122.10 (q, J ¼ 278.5 Hz), 126.89, 122.92, 122.12 (q, J ¼ 278.5 Hz), 113.28, 61.83 (q, J ¼ 37.8
112.79, 61.78 (q, J ¼ 37.8 Hz), 28.60. 19F NMR (471 MHz, CDCl3) Hz), 47.53, 35.46, 29.83, 25.11, 24.73. 19F NMR (471 MHz,
+
+
d ꢀ73.02. HRMS (ESI): calculated for C11H9F3N2O2 : 259.0689 CDCl3) d ꢀ72.98. HRMS (ESI): calculated for C17H19F3N2O2 :
[M + H]+, found: 259.0686.
341.1472 [M + H]+, found: 341.1476.
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123.12 (q, J ¼ 278.5 Hz), 114.58, 63.02 (q, J ¼ 37.8 Hz), 44.00. 19
F
Methyl-2-(2-oxo-3-(2,2,2-triuoroethoxy)quinoxalin-1(2H)-yl)
acetate (8)
NMR (471 MHz, CDCl3) d ꢀ72.92. HRMS (ESI): calculated for
+
C
17H12ClF3N2O2 : 369.0612 [M + H]+, found: 369.0615.
White solid (73% yield), mp 133–134 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.67 (dd, J ¼ 8.0, 1.4 Hz, 1H), 7.47–7.41 (m, 1H), 7.37–
7.31 (m, 1H), 7.06 (dd, J ¼ 8.3, 0.7 Hz, 1H), 5.07 (s, 2H), 4.90 (q, J
¼ 8.3 Hz, 2H), 3.78 (s, 3H). 13C NMR (126 MHz, CDCl3) d 167.30,
151.79, 149.97, 131.26, 130.04, 128.39, 128.23, 124.57, 123.09 (q,
J ¼ 278.5 Hz), 113.24, 62.98 (q, J ¼ 37.8 Hz), 52.95, 43.75. 19F
1-(3-Methylbenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (13)
White solid (78% yield), mp 127–128 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.37–7.33 (m, 1H), 7.30–
7.26 (m, 2H), 7.23–7.18 (m, 1H), 7.07 (d, J ¼ 5.6 Hz, 3H), 5.49 (s,
2H), 4.93 (q, J ¼ 8.3 Hz, 2H), 2.30 (s, 3H). 13C NMR (126 MHz,
CDCl3) d 152.13, 150.47, 138.82, 134.83, 131.51, 130.22, 128.81,
128.65, 128.14, 127.95, 127.60, 124.22, 124.06, 123.15 (q, J ¼
278.5 Hz), 114.73, 62.98 (q, J ¼ 37.8 Hz), 46.47, 21.41. 19F NMR
NMR (471 MHz, CDCl3) d ꢀ73.00. HRMS (ESI): calculated for
+
C
13H11F3N2O4 : 317.0744 [M + H]+, found: 317.0746.
tert-Butyl-2-(2-oxo-3-(2,2,2-triuoroethoxy)quinoxalin-1(2H)-
yl)acetate (9)
White solid (70% yield), mp 127–128 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (dd, J ¼ 8.0, 1.4 Hz, 1H), 7.47–7.41 (m, 1H), 7.35–
7.29 (m, 1H), 7.05 (dd, J ¼ 8.3, 0.7 Hz, 1H), 4.97 (s, 2H), 4.90 (q, J
¼ 8.3 Hz, 2H), 1.46 (s, 9H). 13C NMR (126 MHz, CDCl3) d 165.76,
151.84, 149.96, 131.39, 130.00, 128.21, 128.16, 124.40, 123.09 (q,
J ¼ 278.5 Hz), 113.32, 83.41, 62.93 (q, J ¼ 37.8 Hz), 44.54, 27.96.
(471 MHz, CDCl3) d ꢀ72.94. HRMS (ESI): calculated for
+
C
18H15F3N2O2 : 349.1159 [M + H]+, found: 349.1155.
1-(3-Chlorobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (14)
19F NMR (471 MHz, CDCl3) d ꢀ73.01. HRMS (ESI): calculated for
White solid (72% yield), mp 149–150 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.67 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.40–7.35 (m, 1H), 7.31
(td, J ¼ 7.8, 1.2 Hz, 1H), 7.26 (d, J ¼ 4.7 Hz, 3H), 7.19 (dd, J ¼ 8.3,
0.8 Hz, 1H), 7.17–7.10 (m, 1H), 5.49 (s, 2H), 4.93 (q, J ¼ 8.3 Hz,
2H). 13C NMR (126 MHz, CDCl3) d 152.03, 150.38, 136.92,
134.96, 131.23, 130.28, 130.23, 128.28, 128.20, 128.15, 127.11,
125.19, 124.47, 123.11 (q, J ¼ 278.5 Hz), 114.38, 63.04 (q, J ¼ 37.8
Hz), 45.91. 19F NMR (471 MHz, CDCl3) d ꢀ72.94. HRMS (ESI):
calculated for C17H12ClF3N2O2+: 369.0612 [M + H]+, found:
369.0615.
+
C
16H17F3N2O4 : 359.1213 [M + H]+, found: 359.1216.
1-Benzyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one (10)
White solid (80% yield), mp 126–127 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (d, J ¼ 7.8 Hz, 1H), 7.31 (ddd, J ¼ 22.1, 13.2, 5.1 Hz,
8H), 5.52 (s, 2H), 4.92 (q, J ¼ 8.2 Hz, 2H). 13C NMR (126 MHz,
CDCl3) d 152.11, 150.45, 134.91, 131.44, 130.22, 128.98, 128.15,
128.00, 127.87, 127.03, 124.27, 122.05 (q, J ¼ 278.5 Hz), 114.67,
62.98 (q, J ¼ 37.8 Hz), 46.42. 19F NMR (471 MHz, CDCl3)
d ꢀ72.94. HRMS (ESI): calculated for C17H13F3N2O2+: 335.1002
[M + H]+, found: 335.1008.
1-(3-Bromobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (15)
1-(2-Fluorobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (11)
White solid (75% yield), mp 154–155 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.67 (dd, J ¼ 7.9, 1.5 Hz, 1H), 7.44–7.35 (m, 3H), 7.33–
7.28 (m, 1H), 7.22–7.17 (m, 3H), 5.48 (s, 2H), 4.93 (q, J ¼ 8.3 Hz,
2H). 13C NMR (126 MHz, CDCl3) d 152.02, 150.37, 137.19,
131.22, 131.15, 130.54, 130.22, 129.98, 128.30, 128.15, 125.66,
124.48, 123.11 (q, J ¼ 278.5 Hz), 123.10, 114.37, 63.04 (q, J ¼ 37.8
Hz), 45.84. 19F NMR (471 MHz, CDCl3) d ꢀ72.94. HRMS (ESI):
calculated for C17H12BrF3N2O2+: 413.0107 [M + H]+, found:
413.0109.
White solid (70% yield), mp 141–142 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.40–7.35 (m, 1H), 7.31–
7.28 (m, 1H), 7.26–7.23 (m, 2H), 7.15–7.07 (m, 2H), 7.05–7.00
(m, 1H), 5.58 (s, 2H), 4.93 (q, J ¼ 8.3 Hz, 2H). 13C NMR (126
MHz, CDCl3) d 160.30 (d, J ¼ 245.7 Hz), 152.02, 150.62, 131.15,
130.17, 129.65 (d, J ¼ 7.6 Hz), 128.72 (d, J ¼ 3.8 Hz), 128.36,
128.03, 124.76 (d, J ¼ 3.8 Hz), 124.43, 123.15 (q, J ¼ 278.5 Hz),
122.00 (d, J ¼ 13.8 Hz), 115.59 (d, J ¼ 21.4 Hz), 114.26 (d, J ¼ 2.5
Hz), 63.00 (q, J ¼ 37.8 Hz), 39.83 (d, J ¼ 5.0 Hz). 19F NMR (471
MHz, CDCl3) d ꢀ72.95, ꢀ118.26. HRMS (ESI): calculated for
+
C
17H12F4N2O2 : 353.0908 [M + H]+, found: 353.0905.
1-(4-Methylbenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (16)
1-(2-Chlorobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (12)
White solid (83% yield), mp 171–172 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.63 (dd, J ¼ 8.2, 1.5 Hz, 1H), 7.36–7.32 (m, 1H), 7.29–
White solid (69% yield), mp 150–151 ꢁC. 1H NMR (500 MHz, 7.25 (m, 2H), 7.17 (d, J ¼ 8.1 Hz, 2H), 7.11 (d, J ¼ 8.0 Hz, 2H),
CDCl3) d 7.67 (dd, J ¼ 7.8, 1.6 Hz, 1H), 7.45 (dd, J ¼ 8.0, 0.9 Hz, 5.47 (s, 2H), 4.91 (q, J ¼ 8.3 Hz, 2H), 2.30 (s, 3H). 13C NMR (126
1H), 7.36–7.32 (m, 1H), 7.30 (td, J ¼ 7.6, 1.3 Hz, 1H), 7.22 (td, J ¼ MHz, CDCl3) d 152.11, 150.44, 137.63, 131.91, 131.45, 130.21,
7.9, 1.2 Hz, 1H), 7.13–7.08 (m, 1H), 7.04 (dd, J ¼ 8.2, 1.1 Hz, 1H), 129.62, 128.11, 127.95, 127.07, 124.19, 123.16 (q, J ¼ 278.5 Hz),
6.81 (d, J ¼ 7.7 Hz, 1H), 5.61 (s, 2H), 4.94 (q, J ¼ 8.3 Hz, 2H). 13
C
114.69, 62.95 (q, J ¼ 37.8 Hz), 46.20, 21.08. 19F NMR (471 MHz,
+
NMR (126 MHz, CDCl3) d 152.02, 150.47, 132.63, 131.92, 131.15, CDCl3) d ꢀ72.94. HRMS (ESI): calculated for C18H15F3N2O2 :
130.18, 129.82, 128.99, 128.39, 128.00, 127.39, 127.00, 124.49, 349.1159 [M + H]+, found: 349.1157.
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+
CDCl3) d ꢀ73.12. HRMS (ESI): calculated for C12H11F3N2O3 :
1-(4-Chlorobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (17)
289.0795 [M + H]+, found: 289.0794.
White solid (77% yield), mp 184–185 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (d, J ¼ 7.9 Hz, 1H), 7.39–7.34 (m, 1H), 7.32–7.27
(m, 3H), 7.21 (dd, J ¼ 11.8, 8.3 Hz, 3H), 5.49 (s, 2H), 4.92 (q, J ¼
8.2 Hz, 2H). 13C NMR (126 MHz, CDCl3) d 152.05, 150.39, 133.82,
133.41, 131.22, 130.24, 129.18, 128.51, 128.22, 128.15, 124.43,
6-Chloro-1-methyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (22)
White solid (72% yield), mp 145–146 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.58–7.55 (m, 1H), 7.32–7.29 (m, 1H), 7.29 (s, 1H), 4.88
(q, J ¼ 8.3 Hz, 2H), 3.71 (s, 3H). 13C NMR (126 MHz, CDCl3)
d 152.05, 149.95, 133.96, 132.95, 128.86, 128.52, 124.54, 121.15
(q, J ¼ 278.5 Hz), 113.95, 62.93 (q, J ¼ 37.8 Hz), 29.76. 19F NMR
(471 MHz, CDCl3) d ꢀ73.02. HRMS (ESI): calculated for C11H8-
123.10 (q, J ¼ 278.5 Hz), 114.39, 63.01 (q, J ¼ 37.8 Hz), 45.80. 19
F
NMR (471 MHz, CDCl3) d ꢀ72.96. HRMS (ESI): calculated for
+
C
17H12ClF3N2O2 : 369.0612 [M + H]+, found: 369.0617.
+
ClF3N2O2 : 293.0299 [M + H]+, found: 293.0296.
1-(4-Bromobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (18)
White solid (80% yield), mp 197–198 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (dd, J ¼ 7.9, 1.5 Hz, 1H), 7.45 (d, J ¼ 8.5 Hz, 2H),
7.39–7.34 (m, 1H), 7.30 (td, J ¼ 7.7, 1.3 Hz, 1H), 7.19 (dd, J ¼ 8.3,
1.1 Hz, 1H), 7.16 (d, J ¼ 8.5 Hz, 2H), 5.47 (s, 2H), 4.92 (q, J ¼
8.3 Hz, 2H). 13C NMR (126 MHz, CDCl3) d 152.04, 150.40, 133.94,
132.13, 131.20, 130.24, 128.82, 128.23, 128.15, 124.45, 121.99 (q,
J ¼ 278.5 Hz), 121.88, 114.39, 63.01 (q, J ¼ 37.8 Hz), 45.86. 19F
6-Bromo-1-methyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (23)
White solid (75% yield), mp 151–152 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.50 (dd, J ¼ 7.7, 1.2 Hz, 1H), 7.45–7.42 (m, 2H), 4.88 (q,
J ¼ 8.3 Hz, 2H), 3.71 (s, 3H). 13C NMR (126 MHz, CDCl3)
d 152.20, 149.89, 133.15, 129.07, 128.91, 127.43, 121.15 (q, J ¼
278.5 Hz), 121.76, 116.90, 62.94 (q, J ¼ 37.8 Hz), 29.76. 19F NMR
(471 MHz, CDCl3) d ꢀ73.02. HRMS (ESI): calculated for C11H8-
NMR (471 MHz, CDCl3) d ꢀ72.97. HRMS (ESI): calculated for
+
C
17H12BrF3N2O2 : 413.0107 [M + H]+, found: 413.0106.
+
BrF3N2O2 : 336.9794 [M + H]+, found: 336.9798.
1-(4-Nitrobenzyl)-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (19)
6-Benzoyl-1-methyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
one (24)
White solid (64% yield), mp 193–194 ꢁC. 1H NMR (500 MHz,
CDCl3) d 8.19 (d, J ¼ 8.7 Hz, 2H), 7.69 (dd, J ¼ 7.8, 1.6 Hz, 1H),
7.44 (d, J ¼ 8.7 Hz, 2H), 7.38 (td, J ¼ 7.9, 1.6 Hz, 1H), 7.33 (td, J ¼
7.6, 1.2 Hz, 1H), 7.12 (dd, J ¼ 8.2, 1.0 Hz, 1H), 5.62 (s, 2H), 4.94
(q, J ¼ 8.3 Hz, 2H). 13C NMR (126 MHz, CDCl3) d 151.97, 150.35,
147.66, 142.18, 131.00, 130.27, 128.41, 128.39, 127.87, 124.76,
124.28, 123.06 (q, J ¼ 278.5 Hz), 114.04, 63.09 (q, J ¼ 37.8 Hz),
45.85. 19F NMR (471 MHz, CDCl3) d ꢀ72.96. HRMS (ESI):
calculated for C17H12F3N3O4+: 380.0853 [M + H]+, found:
380.0856.
White solid (58% yield), mp 167–168 ꢁC. 1H NMR (500 MHz,
CDCl3) d 8.08 (d, J ¼ 1.9 Hz, 1H), 8.00 (dd, J ¼ 8.7, 1.9 Hz, 1H),
7.81 (d, J ¼ 7.7 Hz, 2H), 7.64 (t, J ¼ 7.5 Hz, 1H), 7.53 (t, J ¼ 7.7 Hz,
2H), 7.41 (d, J ¼ 8.7 Hz, 1H), 4.90 (q, J ¼ 8.3 Hz, 2H), 3.80 (s, 3H).
13C NMR (126 MHz, CDCl3) d 194.98, 152.62, 150.16, 137.36,
135.12, 133.39, 132.66, 130.25, 129.91, 129.61, 129.31, 128.50,
122.97 (q, J ¼ 278.5 Hz), 114.01, 63.01 (q, J ¼ 37.8 Hz), 29.96. 19
F
NMR (471 MHz, CDCl3) d ꢀ72.93. HRMS (ESI): calculated for
+
C
18H13F3N2O3 : 363.0951 [M + H]+, found: 363.0953.
1-Methyl-6-nitro-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one
(25)
1,6-Dimethyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one
(20)
1
ꢁ
White solid (80% yield), mp 164–165 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.52 (d, J ¼ 8.1 Hz, 1H), 7.15 (d, J ¼ 8.2 Hz, 1H), 7.09 (s,
1H), 4.88 (q, J ¼ 8.4 Hz, 2H), 3.73 (s, 3H), 2.50 (s, 3H). 13C NMR
(126 MHz, CDCl3) d 151.43, 150.32, 138.62, 131.93, 127.86,
127.53, 125.37, 123.15 (q, J ¼ 278.5 Hz), 114.03, 62.70 (q, J ¼ 37.8
Hz), 29.53, 21.86. 19F NMR (471 MHz, CDCl3) d ꢀ73.04. HRMS
(ESI): calculated for C12H11F3N2O2+: 273.0846 [M + H]+, found:
273.0848.
Yellow solid (45% yield), mp 172–173 C. H NMR (500 MHz,
CDCl3) d 7.92 (d, J ¼ 2.4 Hz, 1H), 7.61 (dd, J ¼ 9.0, 2.4 Hz, 1H),
7.27 (d, J ¼ 9.0 Hz, 1H), 4.90 (q, J ¼ 8.3 Hz, 2H), 3.67 (s, 3H). 13
C
NMR (126 MHz, CDCl3) d 151.23, 149.38, 133.57, 133.29, 131.31,
130.89, 130.02, 123.15 (q, J ¼ 278.5 Hz), 115.23, 63.33 (q, J ¼ 37.8
Hz), 29.40. 19F NMR (471 MHz, CDCl3) d ꢀ73.12. HRMS (ESI):
calculated for C11H8F3N3O4 : 304.0540 [M + H]+, found:
+
304.0543.
6-Methoxy-1-methyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-
1,6,7-Trimethyl-3-(2,2,2-triuoroethoxy)quinoxalin-2(1H)-one
one (21)
(26)
White solid (82% yield), mp 169–170 ꢁC. 1H NMR (500 MHz, White solid (80% yield), mp 137–138 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.20 (d, J ¼ 9.1 Hz, 1H), 7.13 (d, J ¼ 2.8 Hz, 1H), 7.08 CDCl3) d 7.40 (s, 1H), 7.04 (s, 1H), 4.87 (q, J ¼ 8.4 Hz, 2H), 3.70 (s,
(dd, J ¼ 9.1, 2.9 Hz, 1H), 4.90 (q, J ¼ 8.3 Hz, 2H), 3.88 (s, 3H), 3H), 2.39 (s, 3H), 2.33 (s, 3H). 13C NMR (126 MHz, CDCl3)
3.72 (s, 3H). 13C NMR (126 MHz, CDCl3) d 156.47, 152.57, d 151.53, 150.24, 137.59, 133.13, 129.99, 128.09, 128.01, 123.21
149.75, 130.82, 126.20, 123.12 (q, J ¼ 278.5 Hz), 116.53, 114.65, (q, J ¼ 278.5 Hz), 114.47, 62.66 (q, J ¼ 37.8 Hz), 29.53, 20.32,
110.27, 62.79 (q, J ¼ 37.8 Hz), 55.75, 29.73. 19F NMR (471 MHz, 19.19. 19F NMR (471 MHz, CDCl3) d ꢀ73.02. HRMS (ESI):
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calculated for C13H13F3N2O2+: 287.1002 [M + H]+, found:
287.1004.
1-Methyl-3-(2,2,3,3-tetrauoropropoxy)quinoxalin-2(1H)-one
(32)
White solid (72% yield), mp 131–132 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.59 (dd, J ¼ 8.0, 1.3 Hz, 1H), 7.43–7.38 (m, 1H), 7.29–
7.25 (m, 1H), 7.23 (d, J ¼ 8.3 Hz, 1H), 6.08 (tt, J ¼ 53.0, 5.0 Hz,
1H), 4.78 (t, J ¼ 12.2 Hz, 2H), 3.67 (s, 3H). 13C NMR (126 MHz,
CDCl3) d 152.11, 150.18, 132.04, 130.06, 128.13, 127.89, 124.25,
113.79, 114.59–106.74 (m), 62.85 (t, J ¼ 27.7 Hz), 29.55. 19F NMR
(471 MHz, CDCl3) d ꢀ124.57, ꢀ139.29. HRMS (ESI): calculated
for C12H10F4N2O2+: 291.0751 [M + H]+, found: 291.0752.
6,7-Dichloro-1-methyl-3-(2,2,2-triuoroethoxy)quinoxalin-
2(1H)-one (27)
White solid (70% yield), mp 160–161 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.74 (s, 1H), 7.38 (s, 1H), 4.87 (q, J ¼ 8.2 Hz, 2H), 3.70 (s,
3H). 13C NMR (126 MHz, CDCl3) d 152.80, 149.63, 132.13,
131.52, 129.23, 128.71, 128.02, 122.89 (q, J ¼ 278.5 Hz), 115.32,
63.09 (q, J ¼ 37.8 Hz), 29.92. 19F NMR (471 MHz, CDCl3)
+
d
ꢀ73.00. HRMS (ESI): calculated for
C
11H7Cl2F3N2O2 :
326.9910 [M + H]+, found: 326.9915.
1-Methyl-3-(4,4,4-triuorobutoxy)quinoxalin-2(1H)-one (33)
White solid (78% yield), mp 108–109 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.55 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.38–7.32 (m, 1H), 7.23
(td, J ¼ 7.8, 1.2 Hz, 1H), 7.21–7.18 (m, 1H), 4.47 (t, J ¼ 6.3 Hz,
2H), 3.65 (s, 3H), 2.32–2.23 (m, 2H), 2.09 (dt, J ¼ 13.5, 6.3 Hz,
2H). 13C NMR (126 MHz, CDCl3) d 153.56, 150.92, 131.64,
130.91, 127.60, 127.26, 127.02 (q, J ¼ 275.9 Hz), 124.02, 113.65,
65.60, 30.74 (q, J ¼ 29.0 Hz), 29.46, 21.46 (q, J ¼ 2.5 Hz). 19F NMR
3-(2,2,2-Triuoroethoxy)quinoxalin-2(1H)-one (28)
1
Brown solid (75% yield), mp 195–196 ꢁC. H NMR (500 MHz,
DMSO) d 12.63 (s, 1H), 7.64–7.60 (m, 1H), 7.49–7.44 (m, 1H),
7.36–7.30 (m, 2H), 5.11 (q, J ¼ 8.9 Hz, 2H). 13C NMR (126 MHz,
DMSO) d 153.28, 150.26, 131.31, 129.74, 128.20, 126.78, 124.23
(q, J ¼ 278.5 Hz), 123.97, 115.66, 62.71 (q, J ¼ 37.8 Hz). 19F NMR
(471 MHz, CDCl3) d ꢀ66.31. HRMS (ESI): calculated for
+
13H13F3N2O2 : 287.1002 [M + H]+, found: 287.1006.
(471 MHz, CDCl3) d ꢀ72.87. HRMS (ESI): calculated for
C
+
C
10H7F3N2O2 : 245.0533 [M + H]+, found: 245.0536.
3-(2,2-Diuoroethoxy)-1-methylquinoxalin-2(1H)-one (34)
White solid (73% yield), mp 128–129 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.58 (dd, J ¼ 7.9, 1.4 Hz, 1H), 7.42–7.37 (m, 1H), 7.26
(td, J ¼ 8.0, 1.2 Hz, 1H), 7.22 (dd, J ¼ 8.4, 0.8 Hz, 1H), 6.19 (tt, J ¼
3-(2,2,2-Triuoroethoxy)-2H-benzo[b][1,4]oxazin-2-one (29)
White solid (78% yield), mp 157–158 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.56 (dd, J ¼ 7.9, 1.5 Hz, 1H), 7.45–7.40 (m, 1H), 7.37–
7.30 (m, 2H), 4.87 (q, J ¼ 8.2 Hz, 2H). 13C NMR (126 MHz, CDCl3)
d 149.02, 148.54, 145.60, 129.02, 128.84, 127.12, 125.95, 122.73
(q, J ¼ 278.5 Hz), 116.35, 63.40 (q, J ¼ 37.8 Hz). 19F NMR (471
55.4, 4.4 Hz, 1H), 4.61 (td, J ¼ 13.0, 4.4 Hz, 2H), 3.67 (s, 3H). 13
C
NMR (126 MHz, CDCl3) d 152.66, 150.49, 131.97, 130.29, 127.89,
127.82, 124.19, 113.76, 112.91 (t, J ¼ 241.9 Hz), 65.34 (t, J ¼ 31.5
Hz), 29.58. 19F NMR (471 MHz, CDCl3) d ꢀ125.03. HRMS (ESI):
calculated for C11H10F2N2O2+: 241.0783 [M + H]+, found:
241.0787.
MHz, CDCl3)
C
d
ꢀ73.17. HRMS (ESI): calculated for
10H6F3NO3 : 246.0373 [M + H]+, found: 246.0373.
+
1-Methyl-3-(2,2,3,3,3-pentauoropropoxy)quinoxalin-2(1H)-
one (30)
3-(2-Fluoroethoxy)-1-methylquinoxalin-2(1H)-one (35)
White solid (80% yield), mp 136–137 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.54 (d, J ¼ 7.9 Hz, 1H), 7.35 (t, J ¼ 7.8 Hz, 1H), 7.23 (t, J
¼ 7.6 Hz, 1H), 7.20–7.17 (m, 1H), 4.83–4.80 (m, 1H), 4.74–4.71
(m, 1H), 4.70–4.67 (m, 1H), 4.66–4.61 (m, 1H), 3.65 (s, 3H). 13C
NMR (126 MHz, CDCl3) d 153.42, 150.78, 131.72, 130.68, 127.59,
127.36, 123.97, 113.65, 80.96 (d, J ¼ 171.4 Hz), 66.03 (d, J ¼ 21.4
Hz), 29.48. 19F NMR (471 MHz, CDCl3) d ꢀ224.30. HRMS (ESI):
White solid (83% yield), mp 110–111 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.65 (dd, J ¼ 8.0, 1.4 Hz, 1H), 7.49 (ddd, J ¼ 8.7, 7.4,
1.5 Hz, 1H), 7.36–7.32 (m, 1H), 7.30 (dd, J ¼ 8.4, 1.0 Hz, 1H), 4.97
(td, J ¼ 12.9, 0.9 Hz, 2H), 3.74 (s, 3H). 13C NMR (126 MHz,
CDCl3) d 152.07, 150.13, 132.15, 129.92, 128.21, 127.88, 124.24,
119.72–117.15 (m), 113.82, 61.73 (t, J ¼ 27.7 Hz), 29.59. 19F NMR
(471 MHz, CDCl3) d ꢀ83.67, ꢀ122.90. HRMS (ESI): calculated for
+
calculated for C11H11FN2O2 : 223.0878 [M + H]+, found:
+
C12H9F5N2O2 : 309.2153 [M + H]+, found: 309.2155.
223.0879.
3-(2,2,3,3,4,4,4-Heptauorobutoxy)-1-methylquinoxalin-2(1H)-
3-(2,2-Diuoroethoxy)-1-ethylquinoxalin-2(1H)-one (36)
one (31)
White solid (70% yield), mp 102–103 ꢁC. 1H NMR (500 MHz,
White solid (79% yield), mp 135–136 ꢁC. 1H NMR (500 MHz, CDCl3) d 7.59 (dd, J ¼ 8.4, 1.5 Hz, 1H), 7.45–7.34 (m, 1H), 7.25 (t,
CDCl3) d 7.66 (dd, J ¼ 8.0, 1.4 Hz, 1H), 7.50–7.46 (m, 1H), 7.36– J ¼ 7.4 Hz, 2H), 6.19 (tt, J ¼ 55.4, 4.4 Hz, 1H), 4.61 (td, J ¼ 13.0,
7.32 (m, 1H), 7.30 (d, J ¼ 8.3 Hz, 1H), 5.01 (t, J ¼ 13.5 Hz, 2H), 4.4 Hz, 2H), 4.29 (q, J ¼ 7.2 Hz, 2H), 1.32 (t, J ¼ 7.2 Hz, 3H). 13
C
3.74 (s, 3H). 13C NMR (126 MHz, CDCl3) d 152.08, 150.11, NMR (126 MHz, CDCl3) d 152.65, 149.96, 130.82, 130.63, 128.11,
132.13, 129.90, 128.18, 127.86, 124.21, 119.72–117.15 (m), 127.87, 123.98, 113.62, 112.94 (t, J ¼ 241.9 Hz), 65.32 (t, J ¼ 31.5
113.80, 61.81 (t, J ¼ 27.7 Hz), 29.57. 19F NMR (471 MHz, CDCl3) Hz), 37.79, 12.36. 19F NMR (471 MHz, CDCl3) d ꢀ124.95. HRMS
d ꢀ80.74, ꢀ119.93, ꢀ127.51. HRMS (ESI): calculated for (ESI): calculated for C12H12F2N2O2+: 255.0940 [M + H]+, found:
13H9F7N2O2 : 359.0625 [M + H]+, found: 359.0627.
255.0946.
+
C
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117.15 (m), 114.47, 61.57 (t, J ¼ 27.7 Hz), 29.50, 20.33, 19.19. 19
F
1-Isopentyl-3-(2,2,3,3-tetrauoropropoxy)quinoxalin-2(1H)-
one (37)
White solid (75% yield), mp 119–120 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.58 (dd, J ¼ 8.0, 1.3 Hz, 1H), 7.40 (t, J ¼ 7.8 Hz, 1H),
7.25 (t, J ¼ 7.6 Hz, 1H), 7.21 (d, J ¼ 8.4 Hz, 1H), 6.10 (tt, J ¼ 53.0,
5.0 Hz, 1H), 4.75 (t, J ¼ 12.1 Hz, 2H), 4.22–4.17 (m, 2H), 1.71–
NMR (471 MHz, CDCl3) d ꢀ83.70, ꢀ122.92. HRMS (ESI): calcu-
+
lated for C14H13F5N2O2 : 337.0970 [M + H]+, found: 337.0972.
6,7-Dichloro-3-(4-methylpiperazin-1-yl)quinoxalin-2(1H)-one
(45)
1
1.69 (m, 1H), 1.59–1.54 (m, 2H), 0.97 (d, J ¼ 6.6 Hz, 6H). 13C Yellow solid (63% yield), mp 234–235 C. H NMR (500 MHz,
NMR (126 MHz, CDCl3) d 152.06, 149.86, 131.14, 130.43, 128.17, DMSO) d 7.46 (s, 1H), 7.39 (s, 1H), 3.92 (s, 4H), 2.45–2.37 (m,
128.10, 124.07, 113.75, 114.43–107.04 (m), 62.94 (t, J ¼ 27.7 Hz), 4H), 2.19 (s, 3H). 13C NMR (126 MHz, DMSO) d 151.78, 151.27,
41.45, 35.81, 26.45, 22.45. 19F NMR (471 MHz, CDCl3) d ꢀ124.65, 132.56, 129.34, 125.49, 125.40, 124.63, 115.39, 54.62, 45.98,
ꢀ139.38. HRMS (ESI): calculated for C16H18F4N2O2+: 347.1377 45.68. HRMS (ESI): calculated for C13H14Cl2N4O+: 313.0618 [M +
ꢁ
[M + H]+, found: 347.1379.
H]+, found: 313.0615.
3,30-Bis(2,2,2-triuoroethoxy)-2,20-biquinoxaline (46)
1-Butyl-3-(2,2,3,3,4,4,4-heptauorobutoxy)quinoxalin-2(1H)-
White solid (50% yield), mp 213–214 ꢁC. 1H NMR (500 MHz,
CDCl3) d 8.24–8.19 (m, 1H), 7.99–7.95 (m, 1H), 7.84–7.78 (m,
1H), 7.74–7.69 (m, 1H), 4.93 (q, J ¼ 8.3 Hz, 2H). 13C NMR (126
MHz, CDCl3) d 153.67, 142.47, 140.16, 139.50, 131.49, 129.71,
128.09, 127.19, 123.16 (q, J ¼ 278.5 Hz), 62.62 (q, J ¼ 37.8 Hz).
one (38)
White solid (74% yield), mp 129–130 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.66 (dd, J ¼ 7.9, 1.3 Hz, 1H), 7.49–7.45 (m, 1H), 7.31
(dd, J ¼ 13.9, 7.6 Hz, 2H), 5.00 (t, J ¼ 13.5 Hz, 2H), 4.31–4.25 (m,
2H), 1.80–1.72 (m, 2H), 1.49 (dd, J ¼ 15.1, 7.5 Hz, 2H), 1.00 (t, J ¼
7.4 Hz, 3H). 13C NMR (126 MHz, CDCl3) d 152.10, 149.84, 131.31,
130.23, 128.13, 128.10, 123.99, 119.72–117.15 (m), 113.85, 61.88
(t, J ¼ 27.7 Hz), 42.65, 29.24, 20.23, 13.76. 19F NMR (471 MHz,
19F NMR (471 MHz, CDCl3) d ꢀ72.93. HRMS (ESI): calculated for
+
C
20H12F6N4O2 : 455.0937 [M + H]+, found: 455.0939.
CDCl3) d ꢀ80.74, ꢀ119.93, ꢀ127.51. HRMS (ESI): calculated for 1-(p-Tolyl)-1H-indole (49)
16H15F7N2O2 : 401.1095 [M + H]+, found: 401.1098.
+
C
Yellow liquid (71% yield), 1H NMR (500 MHz, CDCl3) d 7.67 (d, J
¼ 7.7 Hz, 1H), 7.52 (dd, J ¼ 8.2, 0.6 Hz, 1H), 7.37 (d, J ¼ 8.3 Hz,
2H), 7.31–7.27 (m, 3H), 7.22–7.18 (m, 1H), 7.17–7.13 (m, 1H),
6.65 (dd, J ¼ 3.2, 0.6 Hz, 1H), 2.42 (s, 3H). 13C NMR (126 MHz,
CDCl3) d 137.34, 136.36, 136.02, 130.19, 129.22, 128.11, 124.37,
122.24, 121.10, 120.22, 110.55, 103.23, 21.09.
6-Bromo-3-(2-uoroethoxy)-1-methylquinoxalin-2(1H)-one
(39)
White solid (78% yield), mp 172–173 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.78 (d, J ¼ 2.2 Hz, 1H), 7.52 (dd, J ¼ 8.8, 2.3 Hz, 1H),
7.14 (d, J ¼ 8.9 Hz, 1H), 4.90–4.87 (m, 1H), 4.79 (dd, J ¼ 5.0,
3.6 Hz, 1H), 4.77–4.74 (m, 1H), 4.70 (dd, J ¼ 5.0, 3.6 Hz, 1H), 3.71
(s, 3H). 13C NMR (126 MHz, CDCl3) d 154.16, 150.49, 131.80,
130.93, 130.14, 130.00, 116.64, 115.05, 80.87 (d, J ¼ 171.4 Hz),
Conflicts of interest
There are no conicts to declare.
66.38 (d, J ¼ 21.4 Hz), 29.71. 19F NMR (471 MHz, CDCl3)
+
d
ꢀ224.13. HRMS (ESI): calculated for C11H10BrFN2O2 :
Acknowledgements
300.9983 [M + H]+, found: 300.9989.
This work was supported by Natural Science Foundation of
Shandong Province (ZR2017LB006).
6-Bromo-1-methyl-3-(4,4,4-triuorobutoxy)quinoxalin-2(1H)-
one (40)
White solid (70% yield), mp 119–120 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.78 (d, J ¼ 2.2 Hz, 1H), 7.52 (dd, J ¼ 8.8, 2.2 Hz, 1H),
7.13 (d, J ¼ 8.8 Hz, 1H), 4.53 (t, J ¼ 6.3 Hz, 2H), 3.70 (s, 3H), 2.38–
2.30 (m, 2H), 2.17 (dd, J ¼ 15.3, 6.6 Hz, 2H). 13C NMR (126 MHz,
CDCl3) d 154.24, 150.59, 132.00, 130.82, 130.11, 130.02, 126.98
(q, J ¼ 277.2 Hz), 116.66, 115.03, 65.96, 30.72 (q, J ¼ 29.0 Hz),
29.67, 21.44 (q, J ¼ 3.8 Hz). 19F NMR (471 MHz, CDCl3) d ꢀ66.21.
Notes and references
1 (a) J. Irurre, J. Casas and A. Messeguer, Bioorg. Med. Chem.
Lett., 1993, 3, 179; (b) J. Legros, J. R. Dehli and C. Bolm,
Adv. Synth. Catal., 2005, 347, 19; (c) M. R. Reddy,
N. Shibata, Y. Kondo, S. Nakamura and T. Toru, Angew.
Chem., Int. Ed., 2006, 45, 8163; (d) J.-P. Begue and
D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of
Fluorine, Wiley, Hoboken, 2008.
2 (a) T. Nakai, K. Tanaka and N. Ishikawa, J. Fluorine Chem.,
1977, 9, 89; (b) J. P. Idoux, J. T. Gupton, C. K. McCurry,
A. D. Crews, C. D. Jurss, C. Colon and R. C. Rampi, J. Org.
Chem., 1983, 48, 3771; (c) A. Kamal, T. B. Pratap,
K. V. Ramana, A. V. Ramana and A. H. Babu, Tetrahedron
Lett., 2002, 43, 7353; (d) X. Shen, C. N. Neumann,
C. Kleinlein, N. W. Goldberg and T. Ritter, Angew. Chem.,
Int. Ed., 2015, 54, 5662.
´
´
+
HRMS (ESI): calculated for C13H12BrF3N2O2 : 365.0107 [M + H]+,
found: 365.0108.
1,6,7-Trimethyl-3-(2,2,3,3,3-pentauoropropoxy)quinoxalin-
2(1H)-one (41)
White solid (74% yield), mp 132–133 ꢁC. 1H NMR (500 MHz,
CDCl3) d 7.41 (s, 1H), 7.05 (s, 1H), 4.94 (td, J ¼ 13.0, 0.7 Hz, 2H),
3.71 (s, 3H), 2.40 (s, 3H), 2.34 (s, 3H). 13C NMR (126 MHz, CDCl3)
d 151.58, 150.15, 137.61, 133.10, 130.04, 128.10, 127.96, 119.72–
2024 | RSC Adv., 2020, 10, 2016–2026
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Paper
RSC Advances
3 (a) R. Huang, Y. Huang, X. Lin, M. Rong and Z. Weng, Angew.
Chem., Int. Ed., 2015, 54, 5736; (b) Y. Huang, R. Huang and
S.-R. Zhang, Y.-C. Li and L.-B. Qu, Org. Biomol. Chem.,
2019, 17, 10178–10187.
Z. Weng, Synlett, 2015, 26, 2327; (c) Y. Guo, Y.-D. Li, 10 (a) W. Wei, L. Wang, H. Yue, P. Bao, W. Liu, C. Hu, D. Yang
C. Chen, J.-H. Zhao, H.-W. Liu, D.-H. Liao and Y.-F. Ji, Res.
Chem. Intermed., 2016, 42, 2525; (d) D. Vuluga, J. Legros,
B. Crousse and D. Bonnet-Delpon, Eur. J. Org. Chem., 2009,
3513; (e) K. Zhang, X.-H. Xu and F.-L. Qing, J. Fluorine
Chem., 2017, 196, 24; (f) T. M. Rangarajan, R. Singh,
R. Brahma, K. Devi, R. P. Singh, R. P. Singh and
A. K. Prasad, Chem.–Eur. J., 2014, 20, 14218; (g) L. Yang,
S. Li, L. Cai, Y. Ding, L. Fu, Z. Cai, H. Ji and G. Li, Org.
Lett., 2017, 19, 2746.
4 (a) The European Agency for the Evaluation of Medicinal
Products, Committee for Proprietary Medicinal Products,
London, 2002; (b) D. Nair, J. Scarpello, L. White, L. Freista
dos Santos, I. Vankelecom and A. Livingston, Tetrahedron
Lett., 2001, 42, 8219; (c) C. Garett and K. Prasad, Adv. Synth.
Catal., 2004, 346, 889.
and H. Wang, ACS Sustainable Chem. Eng., 2018, 6, 17252; (b)
J. Fu, J. Yuan, Y. Zhang, Y. Xiao, P. Mao, X. Diao and L. Qu,
Org. Chem. Front., 2018, 5, 3382; (c) L. Hu, J. Yuan, J. Fu,
T. Zhang, L. Gao, Y. Xiao, P. Mao and L. Qu, Eur. J. Org.
Chem., 2018, 4113; (d) S. Liu, Y. Huang, F.-L. Qing and
X.-H. Xu, Org. Lett., 2018, 20, 5497; (e) J. Yuan, J. Fu, J. Yin,
Z. Dong, Y. Xiao, P. Mao and L. Qu, Org. Chem. Front.,
2018, 5, 2820; (f) W. Zhang, Y.-L. Pan, C. Yang, L. Chen,
X. Li and J.-P. Cheng, J. Org. Chem., 2019, 84, 7786; (g)
W. Xue, Y. Su, K.-H. Wang, R. Zhang, Y. Feng, L. Cao,
D. Huang and Y. Hu, Org. Biomol. Chem., 2019, 17, 6654;
(h) L. X. Liu, N. Pan, W. Sheng, L. Su, L. Liu, J. Y. Dong,
Y. B. Zhou and S. F. Yin, Adv. Synth. Catal., 2019, 361,
4126; (i) Z. Yan, B. Sun, X. Zhang, X. Zhuang, J. Yang,
W. Su and C. Jin, Chem.–Asian J., 2019, 14, 3344; (j)
L.-Y. Xie, L.-L. Jiang, J.-X. Tan, Y. Wang, X.-Q. Xu,
B. Zhang, Z. Cao and W.-M. He, ACS Sustainable Chem.
Eng., 2019, 7, 14153.
5 (a) L.-L. Shi, H. Zhou, J.-F. Wu and X. Li, Mini-Rev. Org.
Chem., 2015, 12, 96; (b) L. Shi, W. Hu, J. Wu, H. Zhou,
H. Zhou and X. Li, Mini-Rev. Med. Chem., 2018, 18, 392; (c)
A. Carta, S. Piras, G. Loriga and G. Paglietti, Mini-Rev. Med. 11 (a) K. Yin and R. Zhang, Org. Lett., 2017, 19, 1530; (b) J. Yuan,
Chem., 2006, 6, 1179; (d) X. Li, K. Yang, W. Li and W. Xu,
Drugs Future, 2006, 31, 979; (e) T. Ishi-i, K. Yaguma,
R. Kuwahara, Y. Taguri and S. Mataka, Org. Lett., 2006, 8, 585.
6 (a) F. Wang, B.-L. Hu, L. Liu, H.-Y. Tu and X.-G. Zhang, J. Org.
Chem., 2017, 82, 11247; (b) H. Mtiraoui, K. Renault,
S. Liu and L. Qu, Adv. Synth. Catal., 2017, 359, 4197; (c) K. Yin
and R. Zhang, Synlett, 2018, 29, 597; (d) M. Noikham,
T. Kittikool and S. Yotphan, Synthesis, 2018, 50, 2337; (e)
B. Ramesh, C. R. Reddy, G. R. Kumar and B. V. S. Reddy,
Tetrahedron Lett., 2018, 59, 628.
M. Sanselme, M. Msaddek, P.-Y. Renard and C. Sabot, Org. 12 (a) X. Zeng, C. Liu, X. Wang, J. Zhang, X. Wang and Y. Hu,
Biomol. Chem., 2017, 15, 3060; (c) R. Klemme, C. Bentz,
T. Zukowski, L. Schefzig, D. Lentz, H.-U. Reissig and
R. Zimmer, Synthesis, 2016, 48, 1491; (d) T. Yang, H. Zhu
and W. Yu, Org. Biomol. Chem., 2016, 14, 3376; (e) D. Li,
H. Ma and W. Yu, Adv. Synth. Catal., 2015, 357, 3696; (f)
Org. Biomol. Chem., 2017, 15, 8929; (b) J.-W. Yuan, J.-H. Fu,
S.-N. Liu, Y.-M. Xiao, P. Mao and L.-B. Qu, Org. Biomol.
Chem., 2018, 16, 3203; (c) L.-Y. Xie, S. Peng, T.-G. Fan,
Y.-F. Liu, M. Sun, L.-L. Jiang, X.-X. Wang, Z. Cao and
W.-M. He, Sci. China: Chem., 2019, 62, 460.
H. Jiang, X. An, K. Tong, T. Zheng, Y. Zhan and S. Yu, 13 (a) Z. Wei, S. Qi, Y. Xu, H. Liu, J. Wu, H.-S. Li, C. Xia and
Angew. Chem., Int. Ed., 2015, 54, 4055; (g) X.-D. An and
S. Yu, Org. Lett., 2015, 17, 2692.
7 (a) Q. Ke, G. Yan, J. Yu and X. Wu, Org. Biomol. Chem., 2019,
17, 5863; (b) P. Mao, J. Zhu, J. Yuan, L. Yang, Y. Xiao and
C. Zhang, Chin. J. Org. Chem., 2019, 39, 1529.
G. Duan, Adv. Synth. Catal., 2019, 361, 5490; (b) J. Wang,
B. Sun, L. Zhang, T. Xu, Y. Xie and C. Jin, Asian J. Org.
Chem., 2019, 8, 1942; (c) L. Wang, Y. Zhang, F. Li, X. Hao,
H.-Y. Zhang and J. Zhao, Adv. Synth. Catal., 2018, 360,
3969; (d) W. Xue, Y. Su, K.-H. Wang, L. Cao, Y. Feng,
W. Zhang, D. Huang and Y. Hu, Asian J. Org. Chem., 2019,
8, 887.
8 (a) M. Gao, Y. Li, L. Xie, R. Chauvin and X. Cui, Chem.
Commun., 2016, 52, 2846; (b) J. Wang, J. Li, Y. Wei, J. Yang
and C. Huo, Org. Chem. Front., 2018, 5, 3534; (c) Y. Kim 14 (a) G. Hong, J. Yuan, J. Fu, G. Pan, Z. Wang, L. Yang, Y. Xiao,
and D. Y. Kim, Tetrahedron Lett., 2018, 59, 2443; (d)
W.-P. Mai, J.-W. Yuan, J.-L. Zhu, Q.-Q. Li, L. R. Yang,
Y.-M. Xiao, P. Mao and L.-B. Qu, ChemistrySelect, 2019, 4,
11066.
P. Mao and X. Zhang, Org. Chem. Front., 2019, 6, 1173; (b)
L. Wang, H. Liu, F. Li, J. Zhao, H.-Y. Zhang and Y. Zhang,
Adv. Synth. Catal., 2019, 361, 2354; (c) C. Jin, X. Zhuang,
B. Sun, D. Li and R. Zhu, Asian J. Org. Chem., 2019, 8, 1490.
9 (a) A. Gupta, M. S. Deshmukh and N. Jain, J. Org. Chem., 15 (a) L. Zhao, L. Wang, Y. Gao, Z. Wang and P. Li, Adv. Synth.
2017, 82, 4784; (b) T. T. Hoang, T. A. To, V. T. T. Cao,
A. T. Nguyen, T. T. Nguyen and N. T. S. Phan, Catal.
Commun., 2017, 101, 20; (c) W. Wei, L. Wang, P. Bao,
Y. Shao, H. Yue, D. Yang, X. Yang, X. Zhao and H. Wang,
Catal., 2019, 361, 5363; (b) J. Zhou, P. Zhou, T. Zhao, Q. Ren
and J. Li, Adv. Synth. Catal., 2019, 361, 5371; (c) Q. Yang,
X. Han, J. Zhao, H.-Y. Zhang and Y. Zhang, J. Org. Chem.,
2019, 84, 11417.
Org. Lett., 2018, 20, 7125; (d) Q. Yang, Y. Zhang, Q. Sun, 16 (a) Q.-H. Teng, Y. Yao, W.-X. Wei, H.-T. Tang, J.-R. Li and
K. Shang, H.-Y. Zhang and J. Zhao, Adv. Synth. Catal., 2018,
360, 4509; (e) Q. Yang, Z. Yang, Y. Tan, J. Zhao, Q. Sun,
H.-Y. Zhang and Y. Zhang, Adv. Synth. Catal., 2019, 361,
Y.-M. Pan, Green Chem., 2019, 21, 6241; (b) L.-Y. Xie,
Y.-L. Chen, L. Qin, Y. Wen, J.-W. Xie, J.-X. Tan, Y. Huang,
Z. Cao and W.-M. He, Org. Chem. Front., 2019, 6, 3950.
1662; (f) J.-W. Yuan, J.-L. Zhu, B. Li, L.-Y. Yang, P. Mao, 17 J. Xu, H. Yang, H. Cai, H. Bao, W. Li and P. Zhang, Org. Lett.,
2019, 21, 4698.
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View Article Online
RSC Advances
Paper
18 (a) K.-J. Liu, Z.-H. Duan, X.-L. Zeng, M. Sun, Z. Tang, S. Jiang,
Z. Cao and W.-M. He, ACS Sustainable Chem. Eng., 2019, 7,
10293; (b) L.-Y. Xie, T.-G. Fang, J.-X. Tan, B. Zhang, Z. Cao,
L.-H. Yang and W.-M. He, Green Chem., 2019, 21, 3858; (c)
L.-Y. Xie, J. Qu, S. Peng, K.-J. Liu, Z. Wang, M.-H. Ding,
Y. Wang, Z. Cao and W.-M. He, Green Chem., 2018, 20, 760;
(d) B. Liu, F. Jin, T. Wang, X. Yuan and W. Han, Angew.
Chem., Int. Ed., 2017, 56, 12712; (e) B. Yang and Z. Lu, ACS
Catal., 2017, 7, 8362; (f) S. Yang, P. Li, Z. Wang and
L. Wang, Org. Lett., 2017, 19, 3386; (g) L.-Y. Xie, Y.-J. Li,
J. Qu, Y. Duan, J. Hu, K.-J. Liu, Z. Cao and W.-M. He, Green
Chem., 2017, 19, 5642; (h) X. Zhu, P. Li, Q. Shi and
L. Wang, Green Chem., 2016, 18, 6373; (i) X. Wang,
C. Wang, Y. Liu and J. Xiao, Green Chem., 2016, 18, 4605;
(j) X. Cheng, B. Yang, X. Hu, Q. Xu and Z. Lu, Chem.–Eur.
J., 2016, 22, 17566.
Chem. Commun., 2016, 52, 8275; (i) Y. Xiang, Y. Kuang and
J. Wu, Org. Chem. Front., 2016, 3, 901; (j) H. Xiang,
Q. Zhao, Z. Tang, J. Xiao, P. Xia, C. Wang, C. Yang,
X. Chen and H. Yang, Org. Lett., 2017, 19, 146; (k)
H.-T. Qin, S.-W. Wu, J.-L. Liu and F. Liu, Chem. Commun.,
2017, 53, 1696; (l) P. Dai, X. Yu, P. Teng, W.-H. Zhang and
C. Deng, Org. Lett., 2018, 20, 6901; (m) T. Rawner,
E. Lutsker, C. Kaiser and O. Reiser, ACS Catal., 2018, 8,
3950; (n) L. Zou, P. Li, B. Wang and L. Wang, Chem.
Commun., 2019, 55, 3737; (o) L. Zhao, P. Li, H. Zhang and
L. Wang, Org. Chem. Front., 2019, 6, 87; (p) Y. Liu,
X.-L. Chen, K. Sun, X.-Y. Li, F.-L. Zeng, X.-C. Liu, L.-B. Qu,
Y.-F. Zhao and B. Yu, Org. Lett., 2019, 21, 4019; (q)
F.-L. Zeng, K. Sun, X.-L. Chen, X.-Y. Yuan, S.-Q. He, Y. Liu,
Y.-Y. Peng, L.-B. Qu, Q.-Y. Lv and B. Yu, Adv. Synth. Catal.,
2019, 361, 5176.
19 (a) J. M. R. Narayanam and C. R. J. Stephenson, Chem. Soc. 20 (a) C. Xia, K. Wang, G. Wang and G. Duan, Org. Biomol.
Rev., 2011, 40, 102; (b) X. Pan, H. Xia and J. Wu, Org.
Chem. Front., 2016, 3, 1163; (c) D. A. Nagib and
D. W. C. MacMillan, Nature, 2011, 480, 224; (d) P. V. Pham,
D. A. Nagib and D. W. C. MacMillan, Angew. Chem., Int.
Chem., 2018, 16, 2214; (b) J. Han, G. Wang, J. Sun, H. Li,
G. Duan, F. Li and C. Xia, Catal. Commun., 2019, 118, 81;
(c) G. You, K. Wang, X. Wang, G. Wang, J. Sun, G. Duan
and C. Xia, Org. Lett., 2018, 20, 4005.
Ed., 2011, 50, 6119; (e) T. P. Yoon, M. A. Ischay and J. Du, 21 J. P. Edwards and J. D. Venable, Quinoxaline compounds. US
Nat. Chem., 2010, 2, 527; (f) Y. Ye and M. S. Sanford, J. Am.
Chem. Soc., 2012, 134, 9034; (g) L. Li, X. Mu, W. Liu,
20050070527A1, March 2005, Chem. Abstr., 2005, 142,
355284.
Y. Wang, Z. Mi and C.-J. Li, J. Am. Chem. Soc., 2016, 138, 22 S. Haneda, Y. Adachi and M. Hayashi, Tetrahedron, 2009, 65,
5809; (h) X.-L. Yu, J.-R. Chen, D.-Z. Chen and W.-J. Xiao, 10459.
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