Facile synthesis of fluoroalkylated quinolones using fluoroalk-2-ynoates as fluorinated building blocks

Article abstract of DOI:10.1016/j.jfluchem.2019.02.002

In the presence of Na₂CO₃, a variety of fluoroalkylated quinolones were efficiently synthesized from isatins and fluoroalk-2-ynoates in good to excellent yields at room temperature. The reaction can proceed via two different ways with Michael adduct or isatoic anhydride as the key intermediate.

Full text of DOI:10.1016/j.jfluchem.2019.02.002

Accepted Manuscript
Title: Facile Synthesis of Fluoroalkylated Quinolones Using
Fluoroalk-2-ynoates as Fluorinated Building Blocks
Authors: Jun Wu, Hui Zhang, Xiao Ding, Xuefei Tan, Hong C.
Shen, Jie Chen, Weimin He, Hongmei Deng, Liping Song,
Weiguo Cao
PII:
S0022-1139(19)30023-5
DOI:
Reference:
https://doi.org/10.1016/j.jfluchem.2019.02.002
FLUOR 9285
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
12 January 2019
30 January 2019
2 February 2019
Please cite this article as: Wu J, Zhang H, Ding X, Tan X, Shen HC, Chen J, He
W, Deng H, Song L, Cao W, Facile Synthesis of Fluoroalkylated Quinolones Using
Fluoroalk-2-ynoates as Fluorinated Building Blocks, Journal of Fluorine Chemistry
(2019), https://doi.org/10.1016/j.jfluchem.2019.02.002
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Facile
Synthesis
of
Fluoroalkylated
Quinolones
Using
Fluoroalk-2-ynoates as Fluorinated Building Blocks
Jun Wu,‡[a,b] Hui Zhang,‡[c,f] Xiao Ding,[c] Xuefei Tan,[b] Hong C. Shen,[b] Jie
Chen,[c] Weimin He,[c] Hongmei Deng,[f] Liping Song*[a,c] and Weiguo Cao*[c,d,e]
a School of Materials Science and Engineering, Shanghai University, Shanghai
200444, P. R. China.
b
Medicinal Chemistry Department of Roche Innovation Center Shanghai,
Roche R&D Center (China) Ltd., Shanghai 201203, P. R. China.
c
Department of Chemistry, Shanghai University, Shanghai 200444, P. R.
China.
d
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R.
China.
e
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China.
f
Laboratory for Microstructures, Instrumental Analysis and Research Center
of Shanghai University, Shanghai 200444, P. R. China.
‡ Contribute to this work equally.
* Corresponding authors.
E-mail: wgcao@staff.shu.edu.cn; lpsong@shu.edu.cn
Fax: +86-21-66134856
Graphical asbtract

Facile Synthesis of Fluoroalkylated Quinolones Using
Fluoroalk-2-ynoates as Fluorinated Building Blocks
Jun Wu,‡[a,b] Hui Zhang,‡[c,f] Xiao Ding,[c] Xuefei Tan,[b] Hong C. Shen,[b] Jie Chen,[c] Weimin He,[c] Hongmei
Deng,[f] Liping Song*[a,c] and Weiguo Cao*[c,d,e]
a School of Materials Science and Engineering, Shanghai University, Shanghai 200444, P. R. China. b Medicinal
Chemistry Department of Roche Innovation Center Shanghai, Roche R&D Center (China) Ltd., Shanghai
c
d
201203, P. R. China. Department of Chemistry, Shanghai University, Shanghai 200444, P. R. China. State
Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
e
Sciences, Shanghai 200032, P. R. China. Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
f
Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China. Laboratory for
Microstructures, Instrumental Analysis and Research Center of Shanghai University, Shanghai 200444, P. R.
China. ‡ Contribute to this work equally.
In the presence of Na2CO3, a variety of fluoroalkylated quinolones were efficiently synthesized from isatins and
fluoroalk-2-ynoates in good to excellent yields at room temperature. The reaction can proceed via two different
ways with Michael adduct or isatoic anhydride as the key intermediate.
Highlights

Facile Synthesis of Fluoroalkylated Quinolones Using Fluoroalk-2-ynoates as
Fluorinated Building Blocks


An efficient and mild access to fluoroalkylated quinolones
Intramolecular oxidative cyclization
Abstract
In the presence of Na2CO3, a variety of fluoroalkylated quinolones were
efficiently synthesized from isatins and fluoroalk-2-ynoates in good to excellent
yields at room temperature. The reaction can proceed via two different ways
with Michael adduct or isatoic anhydride as the key intermediate.
Keywords: oxidative cyclization, fluoroalkylated quinolone, fluoroalkylated

alkyne, nucleophilic addition
1. Introduction
Nalidixic acid, which was firstly discovered as a by-product in the
synthesis of chloroquine in 1962 and introduced to clinical use in 1967 as
antibiotic [1], led to the beginning of quinolone development in organic
chemistry [2] and medicinal chemistry [3-8]. Besides familiar antibacterial
activities [3], quinolone and its derivatives have other pharmacologically active
profiles for drug discovery since many of them have exhibited excellent
biological and pharmacological activities, such as anti-tubercular [4], anti-HIV
[5], antimalarial [6], anti-inflammatory [7], anti-tumor [8] activity and so forth.
As is well known, the introduction of fluorine or fluoroalkylated groups into
a bioactive molecule has been a common strategy to develop new drugs in
medicinal chemistry [9]. Furthermore, the carboxylic acid moiety at 3-position
of 4-quilolones has been proved to be essential to antibacterial potency [10].
However,
a
survey of literatures showed that efficiently building
3-carboxylate-2-perfluoroalkylated 4-quinolones has still less explored [11].
Usually, there are three fundamentally different strategies (Scheme 1): (i)
introduction of carboxylate and carbonyl groups to 3 and 4 position,
respectively [11a]; (ii) intramolecular condensation [11b]; (iii) insertion of
carbon monoxide via transition-metal catalyzed reactions [11c]. Yet, due to
some limitations in the above methods such as a narrow substrate scope,
harsh reaction conditions or dependence on multistep-prepared starting
materials et al, it is highly desirable to develop more convenient and efficient
approaches for the synthesis of 3-carboxylate-2-fluoroalkylated 4-quinolones
from easily available starting materials.

Scheme 1
Recently, with TBHP as the oxidant and Cs2CO3 as the base, Wu and his
coworkers have developed an efficient transition-metal-free oxidative
cyclization reaction using isatins and alkynes for the facile synthesis of
non-fluoroalkylated 4-quinolones in DMSO at 100 oC [2b].
Inspired by their work and based on our previous studies on the synthesis
of potentially bioactive fluoroalkylated heterocycles [12], herein, we report an
efficient and mild cascade synthesis of 3-carbonyl-2-fluoroalkylated
4-quinolones using fluoroalk-2-ynoates as fluorinated building blocks and
commercially available isatins as starting materials without transition-metal
catalyst. The reaction proceeded smoothly at room temperature in one pot
within a short time to afford structurally diverse desired products; the control
experiments demonstrated two possible pathways for their formation.
2. Results and Discussion
At the beginning, we applied Wu’s standard conditions to the reaction of

isatin 1a and methyl 4,4,4-trifluorobut-2-ynoate 2a, and achieved 28% yield of
3a (Table 1, entry 1). When the reaction temperature was lowered to room
temperature, the yield was improved to 43% (Table 1, entry 2 vs entry 1).
Screening of various inorganic and organic bases indicated that Na2CO3 was
optimal (Table 1, entry 3). Further screening of other solvents (Table 1, entries
10-16) identified DMF as the best (Table 1, entry 13). Other oxidants such as
m-CPBA, Oxone, DDQ, K2S2O8, NaClO and H2O2 all failed to afford better
results than TBHP (Table 1, entry 13 vs entries 17-22).
Table 1 Optimization of the reaction conditionsa
Yield (%)b
Entry Oxidant
Base
Temp. [ oC] Solvent
1
2
3
4
5
6
7
8
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
m-CPBA
Oxone
DDQ
Cs2CO3
Cs2CO3
Na2CO3
K2CO3
K3PO4
KHCO3
NaOH
KOAc
DBU
DIEA
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
100
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
THF
DCM
EtOH
DMF
MeCN
EtOAc
Acetone
DMF
28
43
79
55
53
68
54
17
ND
70
36
Trace
55
88, 84c
46
31
28
21
28
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
DMF
DMF
DMF
DMF
Trace
Trace
Trace
61
K2S2O8
NaClO
H2O2
DMF

a Reaction conditions: isatin 1a (0.4 mmol), methyl 4,4,4-trifluorobut-2-ynoate
2a (0.4 mmol), base (0.8 mmol) and TBHP (0.4 mmol) in solvent (4 mL), rt, 2
h.b The yields were determined by 19F NMR with PhCF3 as internal standard. c
Isolated
yield.
TBHP:
tert-butyl
hydroperoxide;
DDQ:
2,3-dichloro-5,6-dicyano-p-benzoquinone.
With the optimized condition in hand (Table 1, entry 13), we first explored
the substrate scope with respect to E and RF substituents on
fluoroalk-2-ynoates 2 (Table 2). For this purpose, we used substrates 2a to 2e
and 2z to react with isatin 1a. The reactions proceeded smoothly to afford the
desired products 3a-3e and 3z in 65% to 84% yields.
To explore the scope of the protocol with respect to the R substituent on
the isatin ring, we used a series of 4-, 5-, 6- or 7- substituted isatins (1f to 1v).
Generally, the reaction was not evidently sensitive to the electron density of the
phenyl ring in isatin. When R at 4, 5, or 6-position on isatin 1 was either an
electron-donating substituent (Me or OMe) or an electron-withdrawing group
such as F, Cl, Br, I or CF3, all the corresponding products were obtained in
good yields.
However, when isatin 1 bearing a sterically bulky substituent such as
7-CF3, 7-CO2Me or 7-Me, the yield dropped dramatically (Table 2, 3t-3v,
47%-54%).
Finally, disubstituted isatins 1 were examined; the yields were satisfying
(Table 2, 3w, 85%; 3x 51%).
To our delight, 5-bromo-1H-pyrrolo[2,3-b]pyridine-2,3-dione 1y could also
be tolerated under the optimized conditions, affording 86% yield of methyl
6-bromo-4-oxo-2-(trifluoromethyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylate
3y.
Table 2 Scope of fluoroalkylated 4-quinolonesa,b

a
Reactions conditions: isatin divertives 1 (0.4 mmol), fluoroalk-2-ynoates 2
(0.4 mmol), TBHP (0.4 mmol) and Na2CO3 (0.8 mmol) in DMF (4 mL), rt, 2 h. b
Isolated yield.
To gain insight into the mechanism, we conducted two-step control
experiments (Scheme 2, eq.1 and eq.2). In the presence of Na2CO3, treatment
of 1a with 2a in DMF afforded 84% yield of Michael adduct 4 in 5 min. Then,
compound 4 was transformed into 3a smoothly in 88% yield under our
standard conditions, indicating that the desired product formed via a process
with Michael adduct 4 as a key intermediate.

According to Wu et al’s report [2b], however, the final product was
generated through a different way. In their work, isatin reacted with TBHP first
to give the oxidative intermediate isatoic anhydride which underwent further
reaction with methyl 3-phenylpropiolate to achieve the target product. The
existence of their key intermediate isatoic anhydride was demonstrated by the
fact that a trace of this compound was detected by mass spectroscopy.
To confirm their results, we carried out more control experiments
(Scheme 2, eq.3 and eq.4). Under our conditions for 1 h, isatin 1a can be
oxidized by TBHP to give isatoic anhydride 5 in 20% yields. The intermediate 5
reacted with methyl 4,4,4-trifluorobut-2-ynoate 2a in the presence of base to
afford 78% 3a.
Scheme 2 Control experiments under our standard conditions

The above-described results indicated that the cascade reaction
undergoes in two different ways to furnish the same target; one is the isatoic
anhydride-mediated path suggested by Wu group [2b], the other here was
proposed by us as shown in Scheme 3.
Initially, Michael addition of 1a to 2a forms 4 in the presence of base. Then,
intermolecular nucleophilic attack of TBHP to 4 affords intermediate I followed
by Baeyer-Villiger type oxidation rearrangement to generate intermediate II.
The subsequent carbon dioxide elimination and intramolecular cyclization
leads to III which undergoes isomerization to deliver 3a as the final product.
Scheme 3 Proposed reaction mechanism
3. Conclusions
We have developed a simple, practical protocol for access to
2-perfluoroalkylated-4-quinolone derivatives. Mechanism study indicated that
the cascade reaction undergoes in two different ways to form the same target

product. This protocol, which proceeds at room temperature, opens a new
method for transformation of isatin divertives into compounds of medicinal
interest. Further exploration of this reaction is underway in our laboratory.
4. Experimental
4.1. General Information
Reagents including anhydride 5 (Scheme 2, eq.3) and solvents were
purchased from commercially sources and used without further purification.
Fluoroalkynoates 2 were prepared according to the known literature [14].
Melting points were recorded on a WRS-1 instrument and are uncorrected. 1H,
13
19F and C NMR spectra were recorded on a Bruker 400 MHz spectrometer.
All chemical shifts are reported in parts per million downfield (positive) of the
standard: CFCl3 for 19F, TMS for 1H and 13C NMR spectra. Chemical shifts (δ)
are reported in ppm, and coupling constants (J) are in hertz (Hz). The following
abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t
= triplet, q = quartet, m = multiplet, br = broad. IR spectra were obtained on a
NICOLET iS10 FTIR spectrometer. High-resolution mass spectrometry (HRMS)
was conducted on an Agilent Technologies Q-TOF 6530 unit. X-ray analysis
was performed on a Bruker Smart Apex2 CCD spectrometer. All the reactions
in this paper were monitored by UPLC-MS on a UPLC-MS DW3100 unit.
CombiFlash Rf+ was used to purify compounds.
4.2. General procedure for the synthesis of 3a to 3z
A mixture of 1 (0.4 mmol), 2 (0.4 mmol), Na2CO3 (0.8 mmol) and TBHP (0.4
mmol) in DMF (4 mL) was stirred at rt for 2 h. Then, the mixture was poured
into ice-water, acidified with 1N HCl aq. (6 mL). The mixture was extracted with
ethyl acetate (20 mL x 3). The combined organic layer was dried over
anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by
silica gel flash column chromatography to give desired products.

4.2.1 Methyl 4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3a). 91 mg
1
(84% yield), (eluent: PE/EA = 5:1), white solid; mp 207.1-208.3C. H NMR
(400 MHz, CDCl3) δ: 12.80 (br. s, 1H), 8.36 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 7.8
Hz, 1H), 7.92-7.84 (m, 1H), 7.71-7.63 (m, 1H), 4.06 (s, 3H) ppm. 19F NMR (376
MHz, CDCl3) δ: -64.00 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.9,
168.3, 147.2, 145.8 (m), 133.4, 129.9, 128.4, 123.6, 121.1 (q, J = 276.7 Hz),
120.5, 101.7, 53.2 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3072, 2964,
1747, 1627, 1576, 1477, 1296, 1188, 1147, 953, 766, 617. HRMS (ESI) calcd.
for C12H8F3NO3 [M+H] +: 272.0529, found 272.0536.
4.2.2 Methyl 4-oxo-2-(pentafluoroethyl)-1H-quinoline-3-carboxylate (3b). 108
mg (84% yield), (eluent: PE/EA = 6:1), white solid; mp 146.2-147.0C. 1H NMR
(400 MHz, CDCl3) δ: 12.67 (br. s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 8.4
Hz, 1H), 7.90-7.82 (m, 1H), 7.71-7.64 (m, 1H), 4.06 (s, 3H) ppm. 19F NMR (376
MHz, CDCl3) δ: -78.86 (s, CF3), -107.98 (s, CF2) ppm. 13C NMR (101 MHz,
CDCl3) δ: 170.1, 168.0, 146.9, 146.3 (t, J = 28.3 Hz, 1H), 133.2, 130.0, 128.6,
123.4, 120.3, 119.5 (qt, J = 288.0, 36.4 Hz), 112.7 (tq, J = 259.6, 34.3 Hz),
102.3, 53.2 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3076, 2955, 1738, 1628,
1570, 1477, 1290, 1171, 1057, 926, 744, 619. HRMS (ESI) calcd. for
C13H8F5NO3 [M+H] +: 322.0497, found 322.0502.
4.2.3 Methyl 4-oxo-2-(heptafluoropropyl)-1H-quinoline-3-carboxylate (3c). 120
mg (81% yield), (eluent: PE/EA = 6:1), white solid; mp 181.8-183.2C. 1H NMR
(400 MHz, CDCl3) δ: 12.43 (br. s, 1H), 8.39-8.35 (m, 1H), 8.08 (d, J = 8.3 Hz, 1
H), 7.91-7.85 (m, 1H), 7.72-7.66 (m, 1H), 4.05 (s, 3H) ppm. 19F NMR (376 MHz,
CDCl3) δ: -78.66 (t, J = 9.5 Hz, CF3), -104.19 (q, J = 9.5 Hz, CF2), -120.59 (s,
CF2) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.9, 167.6, 147.0, 146.6 (t, J =
27.5 Hz), 133.3, 129.8, 128.6, 123.5, 120.2, 118.6 (m), 111.9 (m), 109.4 (m),
102.8, 53.2 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 2902, 1738, 1535, 1477,
1336, 1217, 1115, 1012, 887, 742, 623. HRMS (ESI) calcd. for C14H8F7NO3
[M+H] +: 372.0465, found 372.0463.

4.2.4 Methyl 4-oxo-2-(difluoromethyl)-1H-quinoline-3-carboxylate (3d). 66 mg
1
(65% yield), (eluent: PE/EA = 5:1), white solid; mp 219.1-220.4C. H NMR
(400 MHz, DMSO-d6) δ: 12.47 (br. s, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.88-7.83
(m, 1H), 7.81-7.75 (m, 1H), 7.50-7.43 (m, 1H), 7.26 (t, J = 52.0 Hz, 1H), 3.81 (s,
3H) ppm. 19F NMR (376 MHz, DMSO-d6) δ: -117.81 (d, J = 51.8 Hz) ppm. 13C
NMR (101 MHz, DMSO-d6) δ: 174.2, 165.6, 142.8 (m), 139.4, 133.7, 125.8,
125.5, 119.8, 114.2, 110.9 (t, J = 242.1 Hz), 52.8 ppm. IR (MIR-ATR, 4000-600
cm-1): νmax = 2831, 1722, 1537, 1479, 1348, 1146, 1068, 974, 752, 685. HRMS
(ESI) calcd. for C12H9F2NO3 [M+H] +: 254.0623, found 254.0622.
4.2.5 Ethyl 4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3e)[11a]. 94
mg (82% yield), (eluent: PE/EA = 5:1), white solid; mp 191.8-193.3C. 1H NMR
(400 MHz, CDCl3) δ: 12.94 (br. s, 1H), 8.36 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.4
Hz, 1H), 7.92-7.80 (m, 1H), 7.71-7.63 (m, 1H), 4.53 (q, J = 7.1 Hz, 2H), 1.47 (t,
19
J = 7.2 Hz, 3H) ppm. F NMR (376 MHz, CDCl3) δ: -63.34 (s, CF3) ppm. 13C
NMR (101 MHz, CDCl3) δ: 169.5, 168.4, 147.2, 145.9 (q, J = 35.2 Hz), 133.3,
129.9, 128.4, 123.5, 121.2 (q, J = 275.8 Hz), 120.6, 101.9, 63.1, 13.6 ppm. IR
(MIR-ATR, 4000-600 cm-1): νmax = 2902, 1720, 1533, 1477, 1290, 1153, 1135,
1103, 1016, 762, 617. HRMS (ESI) calcd. for C13H10F3NO3 [M+H] +: 286.0686,
found 286.0688.
4.2.6 Methyl 5-chloro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3f).
111 mg (91% yield), (eluent: PE/EA = 5:1), white solid; mp 199.0-200.4C. 1H
NMR (400 MHz, DMSO-d6) δ: 12.73 (br. s, 1H), 7.80 (d, J = 7.6 Hz, 1H),
19
7.74-7.68 (m, 1H), 7.46 (d, J = 7.6 Hz, 1H), 3.83 (s, 3H) ppm. F NMR (376
MHz, DMSO-d6) δ: -63.63 (s, CF3) ppm. 13C NMR (101 MHz, DMSO-d6) δ:
173.3, 164.9, 142.5, 134.4 (m), 133.8, 132.4, 128.3, 121.7, 120.3 (q, J = 277.8
Hz), 118.9, 117.1, 53.2 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3387, 2750,
1745, 1618, 1558, 1462, 1284, 1203, 1146, 1008, 811, 646. HRMS (ESI) calcd.
for C12H7ClF3NO3 [M+H] +: 306.0139, found 306.0141.

4.2.7 Methyl 5-bromo-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3g). 124 mg (89% yield), (eluent: PE/EA = 5:1), pale yellow solid; mp
224.0-225.3C. 1H NMR (400 MHz, CDCl3) δ: 13.26 (br. s, 1H), 8.06 (d, J = 8.3
Hz, 1H), 7.95 (d, J = 7.0 Hz, 1H), 7.67-7.60 (m, 1H), 4.07 (s, 3H) ppm. 19F
NMR (376 MHz, CDCl3) δ: -64.43 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ:
169.9, 168.5, 149.3, 146.2 (q, J = 35.5 Hz), 135.6, 132.9, 130.3, 120.8 (q, J =
275.8 Hz), 119.3, 118.0, 102.4, 53.5 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax
= 3394, 2761, 1743, 1560, 1460, 1301, 1203, 1147, 1002, 810, 627. HRMS
(ESI) calcd. for C12H7BrF3NO3 [M+H] +: 349.9634, found 349.9638.
4.2.8 Methyl 5-methyl-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3h). 87 mg (76% yield), (eluent: PE/EA = 5:1), white solid; mp 154.2-156.0C.
1H NMR (400 MHz, CDCl3) δ: 13.23 (br. s, 1H), 8.08-7.75 (m, 1H), 7.77-7.56
(m, 1H), 7.47-7.31 (m, 1H), 4.05 (s, 3H), 2.93 (s, 3H) ppm. 19F NMR (376 MHz,
CDCl3) δ: -64.14 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 170.9, 170.5,
148.9, 145.7 (m), 138.2, 132.8, 131.1, 128.3, 121.1 (q, J = 275.8 Hz), 119.9,
101.5, 53.2, 24.3 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3567, 2953, 1726,
1624, 1542, 1470, 1303, 1207, 1128, 1080, 970, 802, 669. HRMS (ESI) calcd.
for C13H10F3NO3 [M+H] +: 286.0686, found 286.0694.
4.2.9 Methyl 6-fluoro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3i).
1
97 mg (84% yield), (eluent: PE/EA = 6:1), white solid; mp 201.7-202.6C. H
NMR (400 MHz, CDCl3) δ: 12.77 (br. s, 1H), 8.14-8.09 (m, 1H), 7.97-7.92 (m,
1H), 7.66-7.59 (m, 1H), 4.08 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3) δ: -63.99
(s, CF3), -108.90 (dt, J = 8.2, 4.1 Hz, CF) ppm. 13C NMR (101 MHz, CDCl3) δ:
169.8, 167.6 (d, J = 5.1 Hz), 161.7 (d, J = 251.6 Hz), 145.3 (qd, J = 35.3, 3.0
Hz), 144.2, 132.6 (d, J = 8.8 Hz), 123.3 (d, J = 25.7 Hz), 121.7 (d, J = 9.5 Hz),
121.0 (q, J = 276.8 Hz), 107.6 (d, J = 24.2 Hz), 102.1, 53.4 ppm. IR (MIR-ATR,
4000-600 cm-1): νmax = 3081, 2941, 1745, 1574, 1489, 1292, 1187, 1157, 1134,
1012, 823, 627. HRMS (ESI) calcd. for C12H7F4NO3 [M+H] +: 290.0435, found
290.0438.

4.2.10 Methyl 6-chloro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3j). 110 mg (90% yield), (eluent: PE/EA = 6:1), white solid; mp 205.1-206.0C.
1H NMR (400 MHz, CDCl3) δ: 12.80 (br. s, 1H), 8.31 (d, J = 2.3 Hz, 1H), 8.04 (d,
J = 8.9 Hz, 1H), 7.83-7.77 (m, 1H), 4.08 (s, 3H) ppm. 19F NMR (376 MHz,
CDCl3) δ: -64.08 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.7, 167.3,
146.0 (q, J = 35.2 Hz), 145.6, 134.8, 134.2, 131.5, 122.6, 121.3, 121.0 (q, J =
276.7 Hz), 102.4, 53.4 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3091, 2962,
1682, 1566, 1443, 1333, 1144, 1003, 895, 835, 721. HRMS (ESI) calcd. for
C12H7ClF3NO3 [M+H] +: 306.0139, found 306.0140.
4.2.11 Methyl 6-bromo-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3k). 124 mg (89% yield), (eluent: PE/EA = 5:1), pale yellow solid; mp
1
203.8-204.9C. H NMR (400 MHz, CDCl3) δ: 12.79 (br. s, 1H), 8.50 (s, 1H),
8.02-7.85 (m, 2H), 4.08 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3) δ: -64.11 (s,
CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.6, 167.2, 146.1 (q, J = 35.9 Hz),
145.8, 136.8, 131.5, 126.0, 122.8, 121.7, 120.9 (q, J = 275.7 Hz), 102.4, 53.4
ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3398, 2901, 1728, 1568, 1470,
1292, 1209, 1145, 1109, 820, 623. HRMS (ESI) calcd. for C12H7BrF3NO3 [M+H]
+: 349.9634, found 349.9640.
4.2.12 Methyl 6-iodo-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3l).
137 mg (86% yield), (eluent: PE/EA = 5:1), yellow solid; mp 201.0-202.4C. 1H
NMR (400 MHz, CDCl3) δ: 12.81 (br. s, 1H), 8.74 (d, J = 1.8 Hz, 1H), 8.15-8.09
(m, 1H), 7.82 (d, J = 8.8 Hz, 1H), 4.08 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3)
δ: -64.12 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.6, 167.0, 146.2,
146.1 (m), 142.2, 132.5, 131.3, 122.0, 121.0 (q, J = 275.8 Hz), 102.4, 94.3,
53.4 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3078, 2950, 1732, 1576, 1525,
1468, 1286, 1182, 1146, 1107, 827, 621. HRMS (ESI) calcd. for C12H7F3INO3
[M+H] +: 397.9495, found 397.9505.
4.2.13 Methyl 6-methyl-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3m). 88 mg (77% yield), (eluent: PE/EA = 5:1), white solid; mp 197.0-198.6C.

1H NMR (400 MHz, CDCl3) δ: 12.73 (br. s, 1H), 8.13 (s, 1H), 8.00 (d, J = 8.6 Hz,
1H), 7.74-7.68 (m, 1H), 4.06 (s, 3H), 2.59 (s, 3H) ppm. 19F NMR (376 MHz,
CDCl3) δ: -63.86 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 170.0, 167.7,
145.7, 144.9 (q, J = 35.2 Hz), 139.0, 135.5, 129.6, 122.4, 121.2 (q, J = 275.1
Hz), 120.4, 101.7, 53.2, 21.8 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 2881,
1732, 1558, 1531, 1490, 1300, 1186, 1149, 1105, 820, 723, 626. HRMS (ESI)
calcd. for C13H10F3NO3 [M+H] +: 286.0686, found 286.0683.
4.2.14 Methyl 6-methoxy-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3n). 98 mg (81% yield), (eluent: PE/EA = 5:1), white solid; mp 217.7-219.0C.
1H NMR (400 MHz, CDCl3) δ: 12.68 (br. s, 1H), 8.01 (d, J = 9.0 Hz, 1H), 7.58 (d,
19
J = 2.7 Hz, 1 H), 7.53-7.46 (m, 1H), 4.06 (s, 3H), 3.98 (s, 3H) ppm. F NMR
(376 MHz, CDCl3) δ: -63.63 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 170.1,
166.8, 159.5, 143.3 (q, J = 34.5 Hz), 142.9, 131.4, 125.7, 121.6, 121.3 (q, J =
275.1 Hz), 101.9, 101.1, 55.8, 53.2 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax
=
2848, 1728, 1531, 1489, 1402, 1292, 1189, 1140, 1026, 829, 723, 625. HRMS
(ESI) calcd. for C13H10F3NO4 [M+H] +: 302.0635, found 302.0636.
4.2.15 Methyl 7-bromo-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3o). 116 mg (83% yield), (eluent: PE/EA = 6:1), pale yellow solid; mp
1
195.0-195.8C. H NMR (400 MHz, CDCl3) δ: 12.87 (br. s, 1H), 8.31 (s, 1H),
19
8.22 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 8.7 Hz, 1H), 4.07 (s, 3H) ppm. F NMR
(376 MHz, CDCl3) δ: -64.21 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.7,
168.3, 147.8, 147.0 (q, J = 34.5 Hz), 132.3, 132.0, 128.3, 124.9, 120.8 (q, J =
276.6 Hz), 119.3, 102.1, 53.4 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax
=
3066, 2912, 1736, 1578, 1454, 1409, 1303, 1161, 1066, 957, 837, 630. HRMS
(ESI) calcd. for C12H7BrF3NO3 [M+H] +: 349.9634, found 349.9642.
4.2.16 Methyl 4-oxo-2,7-bis(trifluoromethyl)-1H-quinoline-3-carboxylate (3p).
109 mg (80% yield), (eluent: PE/EA = 5:1), white solid; mp 188.2-189.0C. 1H
NMR (400 MHz, CDCl3) δ: 12.92 (br. s, 1H), 8.50 (d, J = 8.6 Hz, 1H), 8.43 (s,
1H), 7.89-7.85 (m, 1H), 4.10 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3) δ: -63.22

(s, CF3), -64.25 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.6, 168.1,
147.2 (q, J = 35.2 Hz), 146.5, 135.0 (q, J = 33.0 Hz), 127.6 (q, J = 4.4 Hz),
125.0, 124.2 (q, J = 2.9 Hz), 123.6 (q, J = 255.5 Hz), 122.4, 120.7 (q, J = 257.5
Hz), 103.1, 53.6 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3084, 2908, 1734,
1581, 1544, 1309, 1124, 1064, 846, 731, 634. HRMS (ESI) calcd. for
C13H7F6NO3 [M+H] +: 340.0403, found 340.0404.
4.2.17 Methyl 7-methoxy-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3q). 92 mg (76% yield), (eluent: PE/EA = 5:1), white solid; mp 204.9-205.7C.
1H NMR (400 MHz, CDCl3) δ: 12.75 (br. s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 7.41 (d,
19
J = 1.3 Hz, 1H), 7.30-7.23 (m, 1H), 4.05 (s, 3H), 3.97 (s, 3H) ppm. F NMR
(376 MHz, CDCl3) δ: -64.03 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 170.0,
167.8, 164.0, 149.6, 146.5 (q, J = 35.0 Hz), 124.8, 121.1, 121.0 (q, J = 275.8
Hz), 114.8, 108.3, 100.5, 55.9, 53.1 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax
=
3084, 2966, 1736, 1631, 1556, 1286, 1201, 1161, 995, 845, 719. HRMS (ESI)
calcd. for C13H10F3NO4 [M+H] +: 302.0635, found 302.0640.
4.2.18 Methyl 8-fluoro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3r). 101 mg (87% yield), (eluent: PE/EA = 6:1), white solid; mp 149.7-151.2C.
1H NMR (400 MHz, DMSO-d6) δ: 12.25 (br. s, 1H), 8.22 (d, J = 7.9 Hz, 1H),
7.84-7.66 (m, 2H), 3.96 (s, 3H) ppm. 19F NMR (376 MHz, DMSO-d6) δ: -63.68
(s, CF3), -123.59 (s, CF) ppm. 13C NMR (101 MHz, DMSO-d6) δ: 165.3, 162.4
(d, J = 2.9 Hz), 157.2 (d, J = 256.0 Hz), 143.3 (q, J = 34.3 Hz), 136.9, 128.5 (d,
J = 8.1 Hz), 123.8, 121.3 (q, J = 275.8 Hz), 119.4 (d, J = 4.4 Hz), 117.0 (d, J =
18.3 Hz), 112.2, 53.5 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3091, 2964,
1664, 1587, 1490, 1344, 1240, 1149, 974, 791, 760. HRMS (ESI) calcd. for
C12H7F4NO3 [M+H] +: 290.0435, found 290.0433.
4.2.19 Methyl 8-chloro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3s). 100 mg (82% yield), (eluent: PE/EA = 6:1), white solid; mp 170.5-171.8C.
1H NMR (400 MHz, CDCl3) δ: 12.90 (br. s, 1H), 8.30-8.25 (m, 1H), 7.99-7.95
19
(m, 1H), 7.62-7.55 (m, 1H), 4.08 (s, 3H) ppm. F NMR (376 MHz, CDCl3) δ:

-64.07 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.8, 168.5, 146.2 (q, J =
35.9 Hz), 143.6, 134.6, 133.5, 128.4, 122.4, 122.1, 120.9 (q, J = 277.7 Hz),
102.3, 53.5 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3095, 2972, 1670, 1585,
1446, 1344, 1282, 1163, 1126, 953, 793, 746. HRMS (ESI) calcd. for
C12H7ClF3NO3 [M+H] +: 306.0139, found 306.0142 .
4.2.20 Methyl 4-oxo-2,8-bis(trifluoromethyl)-1H-quinoline-3-carboxylate (3t).
1
73 mg (54% yield), (eluent: PE/EA = 6:1), white solid; mp 113.1-114.4C. H
NMR (400 MHz, DMSO-d6) δ: 12.07 (br. s, 1H), 8.70 (d, J = 7.8 Hz, 1H), 8.35
19
(d, J = 7.2 Hz, 1H), 7.91-7.86 (m, 1H), 3.96 (s, 3H) ppm. F NMR (376 MHz,
DMSO-d6) δ: -59.08 (s, CF3), -64.16 (s, CF3) ppm. 13C NMR (101 MHz,
DMSO-d6) δ: 165.2, 161.6, 144.5 (q, J = 33.7 Hz), 143.8, 131.2 (q, J = 5.1 Hz),
128.3, 127.6, 126.9 (q, J = 29.3 Hz), 124.1 (q, J = 272.7 Hz), 122.6, 121.3 (q, J
= 284.6 Hz), 111.8, 53.5 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 2976,
1670, 1587, 1446, 1396, 1319, 1107, 953, 798, 721. HRMS (ESI) calcd. for
C13H7F6NO3 [M+H] +: 340.0403, found 340.0411.
4.2.21 Dimethyl 4-oxo-2-(trifluoromethyl)-1H-quinoline-3,8-dicarboxylate (3u).
65 mg (49% yield), (eluent: PE/EA = 3:1), pale yellow solid; mp 121.0-122.3C.
1H NMR (400 MHz, CDCl3) δ: 12.47 (br. s, 1H), 8.60 (d, J = 7.8 Hz, 1H), 8.46 (d,
19
J = 7.5 Hz, 1H), 7.51-7.45 (m, 1H), 4.06 (s, 3H), 3.96 (s, 3H) ppm. F NMR
(376 MHz, CDCl3) δ: -65.52 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 174.5,
168.1, 164.0, 139.1, 136.4, 135.7 (q, J = 36.2 Hz), 133.0, 126.5, 124.3, 119.9
(q, J = 277.3 Hz), 116.8, 115.7, 53.2 ,53.1 ppm. IR (MIR-ATR, 4000-600 cm-1):
νmax = 3188, 2964, 1741, 1601, 1437, 1277, 1151, 1122, 987, 761. HRMS
(ESI) calcd. for C14H10F3NO5 [M+H] +: 330.0584, found 330.0591.
4.2.22 Methyl 8-methyl-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3v). 54 mg (47% yield), (eluent: PE/EA = 8:1), white solid; mp 103.4-104.8C.
1H NMR (400 MHz, CDCl3) δ: 12.71 (br. s, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.70 (d,
19
J = 7.1 Hz, 1H), 7.57-7.51 (m, 1H), 4.06 (s, 3H), 2.77 (s, 3H) ppm. F NMR
(376 MHz, CDCl3) δ: -64.01 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 170.2,

168.3, 146.1, 144.3 (q, J = 35.2 Hz), 138.5, 133.5, 128.1, 121.2 (q, J = 275.1
Hz), 121.1, 120.5, 101.3, 53.1, 17.5 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax
=
2968, 1670, 1583, 1446, 1342, 1284, 1128, 987, 956, 789. HRMS (ESI) calcd.
for C13H10F3NO3 [M+H] +: 286.0686, found 286.0695.
4.2.23
Methyl
5,8-dichloro-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate (3w). 116
mg (85% yield), (eluent: PE/EA = 8:1), white solid; mp 130.1-131.3C. 1H
NMR (400 MHz, DMSO-d6) δ: 7.94 (d, J = 8.3 Hz, 1H), 7.60 (d, J = 8.3 Hz, 1H),
19
3.85 (s, 3H) ppm. F NMR (376 MHz, DMSO-d6) δ: -63.98 (s, CF3) ppm. 13C
NMR (101 MHz, DMSO-d6) δ: 165.2, 164.3, 144.8, 143.9 (q, J = 33.7 Hz),
132.1, 131.8, 130.7, 129.3, 121.6, 121.2 (q, J = 276.6 Hz), 113.4, 53.6 ppm. IR
(MIR-ATR, 4000-600 cm-1): νmax = 3078, 2964, 1670, 1551, 1444, 1338, 1230,
1141, 1009, 962, 890, 817. HRMS (ESI) calcd. for C12H7Cl2F3NO3 [M+H]+:
339.9750, found 339.9747.
4.2.24
Methyl
6-chloro-8-methyl-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxylate
(3x).
1
65 mg (51% yield), (eluent: PE/EA = 8:1), white solid; mp 143.0-143.8C. H
NMR (400 MHz, CDCl3) δ: 12.71 (br. s, 1H), 8.12 (d, J = 2.2 Hz, 1H), 7.63 (d, J
19
= 1.2 Hz, 1H), 4.07 (s, 3H), 2.74 (s, 3H) ppm. F NMR (376 MHz, CDCl3) δ:
-64.08 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 169.9, 167.4, 144.5, 144.4
(q, J = 35.2 Hz), 140.7, 134.2, 134.0, 121.3, 120.1, 121.1 (q, J = 275.1 Hz),
102.1, 53.3, 17.3 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3088, 2958, 1668,
1581, 1448, 1381, 1335, 1220, 1140, 966, 814, 714. HRMS (ESI) calcd. for
C13H9ClF3NO3 [M+H]+: 320.0296, found 320.0302.
4.2.25
Methyl
6-bromo-4-oxo-2-(trifluoromethyl)-1H-1,8-naphthyridine-3-carboxylate
(3y).
121 mg (86% yield), (eluent: PE/EA = 4:1), pale yellow solid; mp
187.4-188.2C. 1H NMR (400 MHz, DMSO-d6) δ: 9.07 (d, J = 2.6 Hz, 1H),
8.65 (d, J = 2.6 Hz, 1H), 3.82 (s, 3H) ppm. 19F NMR (376 MHz, DMSO-d6) δ:

-63.35 (s, CF3) ppm. 13C NMR (101 MHz, DMSO-d6) δ: 173.0, 164.7, 156.0,
149.6, 137.7 (q, J = 37.4 Hz), 136.9, 121.2, 120.4 (q, J = 276.6 Hz), 116.8,
116.5, 53.3 ppm. IR (MIR-ATR, 4000-600 cm-1): νmax = 3034, 2874, 1741, 1595,
1437, 1300, 1159, 1003, 918, 621. HRMS (ESI) calcd. for C11H6BrF3N2O3
[M+H]+: 350.9587, found 350.9592.
4.2.26 3-Diethoxyphosphoryl-2-(trifluoromethyl)-1H-quinolin-4-one (3z). 113
mg (81% yield), (eluent: PE/EA = 5:1), yellow oil. 1H NMR (400 MHz, CDCl3) δ:
13.78 (br. s, 1H), 8.39 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.91-7.84
(m, 1H), 7.70-7.64 (m, 1H), 4.32-4.15 (m, 4H), 1.38 (t, J = 7.0 Hz, 6H) ppm. 19F
NMR (376 MHz, CDCl3) δ: -64.04 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ:
170.8 (d, J = 5.9 Hz), 147.8, 147.6 (qd, J = 35.4, 5.9 Hz), 133.2, 129.6, 128.4,
123.7, 121.1 (d, J = 10.3 Hz), 121.0 (q, J = 277.8 Hz), 95.8 (d, J = 177.5 Hz),
63.8 (d, J = 5.6 Hz), 15.9 (d, J = 6.9 Hz) ppm. IR (MIR-ATR, 4000-600 cm-1):
νmax = 2987, 2646, 1618, 1576, 1487, 1402, 1136, 1014, 964, 768, 642. HRMS
(ESI) calcd. for C14H15F3NO4P [M+H]+: 350.0764, found 350.0764.
4.3.
Procedure
for
the
synthesis
of
Methyl
3-(2,3-dioxoindolin-1-yl)-4,4,4-trifluorobut-2-enoate (4)
A mixture of 1 (1.0 mmol), 2 (1.0 mmol) and Na2CO3 (2.0 mmol) in DMF (10 mL)
was stirred at rt for 5 minutes. Then, the mixture was poured into ice-water (20
mL) and extracted with ethyl acetate (20 mL x 3). The combined organic layer
was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue
was purified by silica gel flash column chromatography to give the desired
product Z-4 and E-4.
4.3.1 Methyl 3-(2,3-dioxoindolin-1-yl)-4,4,4-trifluorobut-2-enoate (4).
Z-4: yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.75-7.71 (m, 1H), 7.65-7.59 (m,
1H), 7.26-7.20 (m, 1H), 6.96 (s, 1H), 6.84 (d, J = 8.1 Hz, 1H), 3.70 (s, 3H) ppm.
13
19F NMR (376 MHz, CDCl3) δ: -69.26 (s, CF3) ppm. C NMR (101 MHz,
CDCl3) δ: 180.4, 161.5, 157.1, 150.6, 138.8, 133.4 (q, J = 37.4 Hz), 127.5 (q, J
= 3.2 Hz), 126.0, 124.9, 117.9, 120.1 (q, J = 277.8 Hz), 111.3, 52.9 ppm. IR

(MIR-ATR, 4000-600 cm-1): νmax = 3091, 2964, 1736, 1606, 1470, 1300, 1203,
1140, 1066, 989, 897, 758, 669. HRMS (ESI) calcd. for C13H8F3NO4 [M+H]+:
300.0478, found 300.0482.
E-4: yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.76-7.62 (m, 2H), 7.29-7.23 (m,
1H), 6.96 (d, J = 7.9 Hz, 1H), 6.63 (s, 1H), 3.91 (s, 3H) ppm.19F NMR (376
MHz, CDCl3) δ: -63.39 (s, CF3) ppm. 13C NMR (101 MHz, CDCl3) δ: 180.3,
161.9, 156.8, 150.1, 139.0, 132.2 (q, J = 2.2 Hz), 129.6 (q, J = 38.9 Hz), 126.0,
125.2, 119.6 (q, J = 277.8 Hz), 117.5, 111.4, 53.1 ppm. IR (MIR-ATR, 4000-600
cm-1): νmax = 3070, 2960, 1736, 1608, 1471, 1257, 1140, 1103, 989, 762.
HRMS (ESI) calcd. for C13H8F3NO4 [M+H]+: 300.0478, found 300.0482.
Acknowledgments:
The authors are grateful to the National Natural Science Foundation of China
(Grant No. 21672138, 21542005, 21272152) for their financial support.
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[13] CCDC 1886947 (3a) contains the supplementary crystallographic
details for this paper. The data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/getstructures. Unit cell parameters (3a): a:
10.591(11) Å, b: 8.228(9) Å, c: 13.484(14) Å; α: 90.00°, β: 97.776(12)°, γ:
90.00°; space group: P2(1)/c.
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