Nucleophilic Substitution of gem-Difluoroalkenes with TMSNu Promoted by Catalytic Amounts of Cs2CO3

Article abstract of DOI:10.1021/acs.joc.9b00999

The efficient and practical nucleophilic cyanation and trifluoromethylation with appropriate trimethylsilyl nucleophiles were developed. Catalytic amounts of cheap and nontoxic Cs₂CO₃ were used to maintain a sufficiently high concentration of nucleophilic anion (CN^- or CF₃^-) which could begin the catalytic cycle. The present methodologies provide diverse functionalized monofluoroalkenes bearing a cyano and trifluoromethyl group with excellent to moderate stereoselectivities.

Full text of DOI:10.1021/acs.joc.9b00999

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Featured Article
Nucleophilic Substitution of gem-Difluoroalkenes with
TMSNu Promoted by Catalytic Amounts of Cs2CO3
Ling-Feng Jiang, Bing-Tao Ren, Bin Li, Guang-Yi Zhang, Yi Peng, Zhen-Yu Guan, and Qing-Hai Deng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00999 • Publication Date (Web): 15 May 2019
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Nucleophilic Substitution of gem-Difluoroalkenes with TMSNu Pro-
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moted by Catalytic Amounts of Cs2CO3
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Ling-Feng Jiang, Bing-Tao Ren, Bin Li, Guang-Yi Zhang, Yi Peng, Zhen-Yu Guan, Qing-Hai Deng*
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials,
Shanghai Normal University, Shanghai 200234, P. R. China
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ABSTRACT
The efficient and practical nucleophilic cyanation and trifluoromethylation with appropriate trimethylsilyl nucleophiles were devel-
oped. Catalytic amounts of cheap and non-toxic Cs2CO3 was used to maintain a sufficiently high concentration of nucleophilic anion
-
(CN- or CF3 ) which could start up the catalytic cycle. The present methodologies provide diverse functionalized monofluoroalkenes
bearing cyano and trifluoromethyl group with excellent to moderate stereoselectivities.
INTRODUCTION
Monofluoroalkenes, due to the unique properties, play a significant role in pharmaceutical/medicinal chemistry, synthetic or-
ganic chemistry and material sciences.1 Consequently, a growing number of efficient methodologies for synthesis of monofluoroal-
kenes have been reported,2, 3 and one of the most common methods is C-F functionalization of readily available gem-difluoroalkenes3,
4 which can be mainly classified into transition metal catalysis (TMC) and nucleophilic vinylic substitution reaction (SNV). Despite
the great advances of this area, several drawbacks including requirement of transition metal as catalyst (for TMC) or excess quantities
of base as additive (for SNV) offered the attractive challenges for further exploration.
In general, a fluoride anion was displaced with nucleophilic anion (Nu-) via addition-elimination processes in SNV reaction of
gem-difluoroalkenes.3b It is reasonable that trimethylsilyl nucleophiles (TMSNu)5 could assist the cleavage of C-F bond in the inter-
mediate A, due to the high fluorophilicity of silicon,6 to form TMSF and product B as well as regenerate nucleophilic anion (Nu-)
(Scheme 1, part 2b). Logically, a catalytic recycle could be realized if catalytic amounts of “Nu-” source was added in the system to
start up the reaction. We postulated that only catalytic amounts of salts bearing oxoanion could dissociate TMSNu reversibly, due to
high oxophilicity of silicon,7 to maintain a sufficiently high concentration of nucleophilic anion which is responsible for nucleophilic
addition to gem-difluoroalkene (Scheme 1, part 2a). Notably, the related reports on catalytic nucleophilic substitution of gem-difluoro-
alkenes is still rare.8 In this context, we report herein that catalytic amounts of Cs2CO3 promoted stereoselective nucleophilic cya-
nation and trifluoromethylation of gem-difluoroalkenes with appropriate trimethylsilyl nucleophiles for providing desired mono-
fluoroalkenes, respectively.
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Scheme 1. Nucleophilic Substitution of gem-Difluoroalkenes with TMSNu Promoted by Catalytic Amounts of Cs2CO3
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RESULTS AND DISCUSSION
2-Fluoroacrylonitriles are an important and attractive type of structural scaffolds that form the basis of many biologically active
molecules.10 However, very few related synthetic methodologies have been described in the literature.11 In 2016, Cao’s group devel-
oped an efficient method for the synthesis of 2-fluoroacrylonitriles by highly stereoselective cyanation of gem-difluoroalkenes using
easily available benzyl nitrile as a cyanating reagent with assistance of excess lithium tert-butoxide under air atmosphere (Scheme 1,
part 1a).11a To the best of our knowledge, catalytic nucleophilic cyanation of gem-difluoroalkenes has been rarely developed.12 Thus,
we commenced our investigations using the cyanation of gem-difluoroalkene 1a with TMSCN as the model reaction to optimize the
reaction conditions (Table 1). Initially, the reaction did not work when it was conducted in the presence of 10 mol % of CuCN in
DMF under nitrogen atmosphere at 100 oC (Table 1, entry 1). Unexpectedly, the desired product 2a was obtained in 37% yield without
any additive in DMF (Table 1, entry 2) and the product was also isolated in 10% yield employing MeCN as a solvent (Table 1, entry
3). Subsequently, adding catalytic amounts of alkali-metal salts could improve the reaction yields dramatically even the reaction was
carried out at room temperature in MeCN (Table 1, entries 4-8). Cesium salts such as Cs2CO3, CsOAc and CsF turned out to be more
effective, and Cs2CO3 provided the best yield (97%) with sole E configuration. In contrast, CsCl and CsBr proved to be unreactive
(Table 1, entries 9 and 10), thus indicating that the counteranion played an important role on catalytic performance. Solvent screening
showed that DMSO was also suitable for this reaction but got lower E/Z selectivity (Table 1, entry 12). Other solvents such as dioxane,
EtOH, toluene, THF and DCM all resulted in no reaction (Table 1, entries 14-18). Excess amounts (3.0 equiv) of TMSCN were
required for high yield. When the amount of TMSCN was changed to 2.0 equiv, the yield of product 2a was decreased to 82% (Table
1, entry 19). Finally, reducing the amount of Cs2CO3 to 5 mol % or 1 mol % still resulted in the product 2a with slightly lower yields
(Table 1, entries 20 and 21). It is notable that the reaction of 1a with TMSCN could be scaled up to gram quantities smoothly and
provided 2a (0.96 g) in 90% yield (Table 1, entry 22).
Table 1. Optimization of the Reaction Conditions of Cyanationa
E/Zc
yieldb (%)
NRd
37
solvent
DMF
time (h)
48
entry
1
cat.
CuCN
--g
n.d.e
n.d.e
n.d.e
n.d.e
n.d.e
2f
3f
4
DMF
48
--g
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
48
2
10
Na2CO3
70
2
0.5
2
5
K2CO3
Cs2CO3
CsOAc
CsF
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6
97h
90
> 50:1
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> 50:1
n.d.e
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n.d.e
n.d.e
11:1
16:1
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CsCl
MeCN
MeCN
DMF
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12
0.5
2
NRd
NRd
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19i
20j
21k
22l
CsBr
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
NMP
90
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64
16:1
n.d.e
dioxane
EtOH
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2
NRd
NRd
NRd
NRd
NRd
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n.d.e
n.d.e
n.d.e
n.d.e
n.d.e
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toluene
THF
DCM
MeCN
MeCN
MeCN
MeCN
1
90
> 50:1
> 50:1
> 50:1
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aReactions were conducted with 1a (0.20 mmol), TMSCN (3.0 equiv), cat. (5 mol %) and solvent (1 mL) under an atmosphere of
nitrogen at room temperature. bYields of isolated products. cThe ratio of E/Z isomer in the crude reaction mixture was determined
by 1H NMR, and the configuration of major isomer was established as E by comparison with the data in reference 6c. dNo Reaction.
eThe compound was not detected. fThe reaction was conducted at 100 oC. gThe reaction was conducted without any catalyst. hThe
isolated product was detemined as sole E configuration through analysis of NMR spectra. i2.0 equiv of TMSCN was used. j5 mol
k
l
% of Cs2CO3 and 0.30 mmol of 1a were used. 1 mol % of Cs2CO3 and 0.30 mmol of 1a were used. Gram-scale reaction: 5.2
mmol of 1a was used and 0.96 g of 2a was obtained.
Scheme 2. Substrate Scope of Cyanationa, b
a Reactions were conducted with 1a (0.30 mmol), TMSCN (3.0 equiv), Cs2CO3 (10 mol %) and MeCN (1 mL) under the atmos-
phere of nitrogen at room temperature. b Yields of isolated products; the ratio of E/Z isomers was determined by 1H NMR and 19
F
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NMR, and the configuration of major isomer was determined as E by comparison with the data in reference 11d. c The reaction
was conducted at 40 oC. d The reaction was conducted at 60 oC. e 20 mol % of Cs2CO3 and 6.0 equiv of TMSCN were used.
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With the optimal reaction conditions in hand (Table 1, entry 6), a range of monosubstituted gem-difluoroalkenes (1b-q) were
reacted with TMSCN to examine the generality of the process (Scheme 2). It should be mentioned that in order to get satisfactory
yields in a shortened time, the reactions of 1b, 1c, 1h-l, and 1q should be performed in higher temperature (40oC or 60oC). Generally,
gem-difluoroalkenes bearing an electron-withdrawing group such as chloro, bromo, trifluoromethyl and cyano groups afforded the
desired products in good to high yields (2b-g, 78%-93%), and the location of the substituent on the phenyl ring of gem-difluoroalkenes
only effected the yields slightly (2e, 2f and 2g). Electron-donating substituents were unfavorable for the transformations, thus product
2i with a para-methyl group and product 2j with a para-tert-butyl group were obtained in 61% and 60% yields, respectively. These
results indicated that the pathway of reaction probably involves a benzyl anion intermediate which was formed through cyanide anion
attack. Other kind of groups on the aryl unit such as 4-phenyl (1k) and 4-thiomethyl (1l) substituents also afforded the product 2k
(78%) and 2l (80%), respectively. 2-(2,2-Difluorovinyl)naphthalene was also a suitable substrate and afforded the corresponding
product 2m in 86% yield. To our delight, 1,3-dichloro-5-(2,2-difluorovinyl)benzene (1n) and sterically hindered substrates (1o and
1p) were also tolerated under the optimized conditions and provided the desired products (2n-p) in high yields (86-92%). In addition,
1,4-bis(2,2-difluorovinyl)benzene (1q) also gave the desired product 2q in a moderate yield (67 %).
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To further evaluate the scope of the methods, several disubstituted gem-difluoroalkenes (1r-w) were subjected to the reaction
(Scheme 2). Symmetrical gem-difluoroalkene 1r got the desired product 2r in 94% yield. In the case of unsymmetrical gem-difluoro-
alkenes as starting materials (1s-v), moderate E/Z selectivity (>= 7:1) was obtained. Finally, 2-fluoro-3-phenyl-3-(p-tolylthio)acrylo-
nitrile (2w) was also obtained with moderate stereoselectivity.13
Scheme 3. Substrate Scope of Trifluoromethylationa, b
a Reactions were conducted with
1 (0.20 mmol), TMSCF3 (2.5 equiv), Cs2CO3 (10 mol %) and DMF (1 mL) under an atmosphere
of nitrogen at room temperature. b Yields of isolated products; the ratio of E/Z isomers was determined by 19F NMR sepectroscopy,
and the configuration of major isomer was determined by analysis of NOESY(1H-19F) spectrum.
Encouraged by the above results, we also explored the defluorinative trifluoromethylation of gem-difluoroalkenes (Scheme 3),
which was few related investigations reported (Scheme 1, part 1b).14 After further optimization of the reaction conditions, DMF was
found as the suitable solvent.15 In this transformation, disubstituted gem-difluoroalkenes16 reacted smoothly to deliver the correspond-
ing products 3a-f in good yields with moderate stereoselectivity (6:1). Monosubstituted gem-difluoroalkenes bearing electron-with-
drawing groups generated the desired products 3g-h in moderate yields with sole Z configuration.
As mentioned in Table 1, the presence of alkali-metal salts bearing oxoanions are crucial for the process. In order to verify the
role of alkali-metal salts and understand the reaction mechanism, series of additional experiments were carried out as described in
Table 2. The reaction of gem-difluoroalkene 1a with NaCN was carried out partly (about 15% of 1a was recovered) in the absence
of Cs2CO3 to afford the desired product 2a in 70% yield by prolonging the reaction time to 4 h (Table 2, entry 1), which demonstrated
that the reaction probably proceeds through a SNV pathway by using “CN-” as a nucleophile. Further screening salts found that K3PO4,
K2HPO4 and tBuOK all showed high catalytic activities (Table 2, entries 2-4). In addition, the type of cation of salts also affected the
reactivity obviously. The usage of 10 mol % of NaCN as a catalyst directly gave 52% yield, which is comparable to the results of
NaOAc and Na2CO3 (Table 2, entries 5-6 and Table 1, entry 4). Zn(CN)2 could not even catalyze the reaction (Table 2, entry 7);
adding extra Zn(OAc)2 (10 mol %), in which zinc ion probably coordinates with cyano anion generated in situ to reduce its concen-
tration, restrained the reaction completely (Table 2, entry 8 vs Table 1, entry 8). Analysis of these data (including the data in Table
1) revealed that Cs2CO3 could dissociate TMSCN reversibly to maintain a sufficiently high concentration of cyano anion, which
nucleophilically attacked gem-difluoroalkene 1 to form the intermediate A. Subsequently, the stereoselective elimination of fluoride11a
from the intermediate A with the assistance of TMSCN provided product 2 and regenerated cyano anion (Scheme 1, Nu = CN).
Table 2. Control Experiments for Mechanistic Investigationsa
time (h)
entry
cat.
yieldb (%)
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NaCN (3.0 equiv)
1c
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4
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7
8
4
2
70d
90
1
2
3
4
5
6
7
8
K3PO4 (10 mol %)
K2HPO4 (10 mol %)
2
88
tBuOK (10 mol %)
NaCN (10 mol %)
12
20
4
96
52
NaOAc (10 mol %)
Zn(CN)2 (10 mol %)
48
2
NRe
Tracef
9
10
11
CsF (10 mol %) + Zn(OAc)2 (10 mol %)
24
aReactions were conducted with 1a (0.30 mmol), TMSCN (3.0 equiv), catalyst and MeCN (1 mL) under an atmosphere of nitrogen
at room temperature. bYields of isolated products. c3.0 equiv of NaCN was used instead of TMSCN, and without Cs2CO3. d15% of
1a was recovered. eNo reaction. fOnly trace product 2a was detected by TLC.
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The conformational analysis of intermediate A (Scheme 1) could explain the different stereochemical outcomes of monosubsti-
tuted gem-difluoroalkenes between cyanation and trifluoromethylation (Figure 1). Rotation of the intermediate A would form two
typically conformational intermediates. Intermediate A2 should be more stable than intermediate A1 because there might be no elec-
tronic repulsion between fluorine atom and aryl group.11a However, intermediate A3 is less stable than intermediate A4 due to the
electronic and stertical repulsions between CF3 group and aryl group.17 Thus, favorable intermediates A2 and A4 could be transformed
to the corresponding products with an excellent stereoselectivity, respectively.
Figure 1. Conformational Analysis of Intermediate A
CONCLUSIONS
We have developed an efficient and practical nucleophilic cyanation and trifluoromethylation of gem-difluoroalkenes with ap-
propriate TMSNu under mild and convenient conditions by using catalytic amounts of Cs2CO3 as a promoter. The reaction can be
readily scaled up to gram amounts and provides diverse monofluoroalkenes with excellent (for monosbustituted difluoroalkenes) to
moderate (for disbustituted difluoroalkenes) E/Z selectivities. Preliminary mechanistic investigations suggested that catalytic amounts
of Cs2CO3 is used to maintain the concentration of nucleophilic anion in the system to start up the catalytic recycle. Further studies
on the mechanisms and the related applications are ongoing in our group.18
EXPERIMENTAL SECTION
General information. All manipulations were maintained under an atmosphere of nitrogen unless otherwise stated. Commer-
cially available reagents were used without further purification. Solvents were predried over activated 4 Å molecular sieves and were
refluxed over magnesium-iodine (methanol, ethanol), potassium (hexane), sodium-benzophenone (tetrahydrofurane) or calcium hy-
dride (dichloroethane, acetonitrile, N, N-Dimethylformamide, dimethyl sulfoxide, N-Methyl pyrrolidone) under an argon atmosphere
and collected by distillation. Column chromatography was performed on silica gel (200 - 300 mesh). NMR studies were performed
on 400 Bruker spectrometers. Infrared spectra were prepared as KBr pellets and were recorded on a Varian Excalibur 3100 series F -
IR spectrometer. Mass spectra were recorded by the mass spectrometry service of Shanghai Institute of Organic Chemistry.
Substrate preparation. The compounds 1a-1y were prepared according to the literatures,4g, 4r, 19 and the known compounds
spectra data are in agreement with the reports. The new compounds 1o, 1w were prepared by the literature method4g, 19a, 19c and the
spectra data are shown in this paper.
1
1-bromo-2-(2,2-difluorovinyl)-4-(trifluoromethyl)benzene (1o). Colorless liquid; 80% yield (1.6 g, 5.6 mmol); H NMR (400
MHz, CDCl3) δ 7.75 (d, J = 1.6 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.36 (dd, J = 8.4, 2.0 Hz, 1H), 5.71 (dd, J = 24.8, 3.4 Hz, 1H);
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13C{1H} NMR (101 MHz, CDCl3) δ 157.2 (dd, J = 299.9, 291.0 Hz), 133.7, 131.6 (dd, J = 8.3, 6.0 Hz), 130.5 (q, J = 32.9 Hz), 127.2
(dd, J = 3.7, 1.8 Hz), 126.0 (ddd, J = 9.7, 3.9, 1.5 Hz), 125.2 (q, J = 3.7 Hz), 123.8 (q, J = 273.4 Hz), 81.3 (dd, J = 33.6, 12.1 Hz);
19F NMR (376 MHz, CDCl3) δ -62.98 (s, 3F), -79.65 (dd, J = 22.0, 3.8 Hz, 1F), -80.94 (dd, J = 25.2, 21.6 Hz, 1F); IR v (neat, cm-1):
2926, 2856, 1729, 1610, 1282, 1085, 916, 827, 736; HRMS (ESI-TOF, m/z): calcd. For C9H4BrF5H [M+H]+: 286.9489, found:
286.9493.
(2,2-difluoro-1-phenylvinyl)(p-tolyl)sulfane (1w). Colorless liquid; 50% yield for two steps (0.34 g, 1.3 mmol); 1H NMR (400
MHz, CDCl3) δ 7.51 (d, J = 7.8 Hz, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.26 – 7.21 (m, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz,
2H), 2.26 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3) δ 157.0 (dd, J = 304.6, 289.6 Hz), 136.7, 132.7 (d, J = 4.2 Hz), 130.8 (t, J = 2.4
Hz), 129.9, 129.0, 128.9 (t, J = 3.5 Hz), 128.7, 128.5, 128.1, 21.1; 19F NMR (564 MHz, CDCl3) δ -75.88 (d, J = 14.2 Hz, 1F), -78.07
(d, J = 14.2 Hz, 1F); IR v (neat, cm-1): 3076, 3028, 1684, 1265, 1009, 814, 735, 687; HRMS (ESI-TOF, m/z): calcd. For C9H4BrF5H
[M+H]+: 263.0701, found: 263.0711.
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General procedure for the synthesis of product 2 and gram-scale reaction. An oven-dried 10 mL Schlenk tube was charged
with Cs2CO3 (0.03 mmol, 9.8 mg), TMSCN (0.90 mmol, 89 mg), 1 (0.30 mmol), and then anhydrous MeCN (1.0 mL) was added
through syringe. After stirring in an oil bath preheated at a specified temperature for several hours, the solvent was removed in vacuo.
Purification of the residue by silica gel column chromatography afforded the desired product 2.
(E)-methyl 4-(2-cyano-2-fluorovinyl)benzoate (2a).11c Reaction temperature: rt; reaction time: 0.5 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); White solid; 97% yield (59.7 mg, 0.29 mmol); The same reaction has been
carried on gram scale employing an oven-dried 50 mL Schlenk tube was charged with Cs2CO3 (0.52 mmol, 169 mg), TMSCN (15.6
mmol, 1.55 g), 1a (5.2 mmol, 1.03 g), and then anhydrous MeCN (10 mL) was added through syringe. After stirring at rt for 1 h, the
solvent was removed in vacuo. Purification of the residue by silica gel column chromatography (PE : EtOAc = 50 : 1) afforded the
desired product 2a (90%, 0.96 g); 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.09 (d, J=16.0
Hz, 1H), 3.94 (s, 3H).
(E)-3-(4-chlorophenyl)-2-fluoroacrylonitrile (2b).11a Reaction temperature: 40 oC; reaction time: 16 h; petroleum ether; TLC: Rf
= 0.6 (PE, UV); Colorless liquid; 78% yield (42.5 mg; 0.23 mmol); 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.6 Hz, 2H), 7.41 (d,
J = 8.6 Hz, 2H), 7.02 (d, J = 16.4 Hz, 1H).
(E)-3-(4-bromophenyl)-2-fluoroacrylonitrile (2c).11b Reaction temperature: 40 oC; reaction time: 16 h; petroleum ether; TLC: Rf
= 0.6 (PE, UV); Colorless liquid; 80% yield (54.2 mg, 0.24 mmol); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.45 (d,
J = 8.4 Hz, 2H), 7.00 (d, J = 16.2 Hz, 1H).
(E)-2-fluoro-3-(4-(trifluoromethyl)phenyl)acrylonitrile (2d). Reaction temperature: rt; reaction time: 0.5 h; petroleum ether;
TLC: Rf = 0.6 (PE, UV); Colorless liquid; 89% yield (57.6 mg, 0.27 mmol); 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 0.8 Hz, 4H),
7.10 (d, J = 15.8 Hz, 1H).
(E)-4-(2-cyano-2-fluorovinyl)benzonitrile (2e). Reaction temperature: rt; reaction time: 0.5 h; petroleum ether/ ethylacetate =
50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); White solid (mp:121 - 122 oC); 93% yield (48.1 mg 0.28 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.69 (d, J =8.0 Hz, 2H), 7.08 (d, J =16.0 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 133.1,
133.0 (d, J = 246.8Hz), 132.9 (d, J = 7.1 Hz), 129.1 (d, J = 3.2 Hz), 124.3 (d, J = 25.6 Hz), 118.0 , 114.3, 111.8 (d, J = 46.6 Hz); 19
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NMR (376 MHz, CDCl3) δ -115.73 (d, J = 15.6 Hz, 1F); IR v (neat, cm-1): 3043, 2922, 2225, 1646, 1502, 1260, 1222, 908, 834;
HRMS (ESI-TOF, m/z): calcd. For C10H5FN2H [M+H]+: 173.0510, found: 173.0509.
(E)-3-(2-cyano-2-fluorovinyl)benzonitrile (2f). Reaction temperature: rt; reaction time: 1 h; petroleum ether/ ethylacetate = 50:1;
TLC: Rf = 0.5 (PE / EA = 10:1, UV); White solid (mp: 87 - 88 oC); 91% yield (46.9 mg, 0.27 mmol); 1H NMR (400 MHz, CDCl3) δ
7.87 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.06 (d, J = 15.4 Hz, 1H); 13C{1H} NMR
(101 MHz, CDCl3) δ 133.7 (d, J = 1.6 Hz), 132.6 (d, J = 245.6 Hz), 132.2, 132.1 (d, J = 5.8 Hz), 130.3, 129.8 (d, J = 7.2 Hz), 123.9
(d, J = 25.6 Hz), 117.7, 113.9, 111.8 (d, J = 46.7 Hz); 19F NMR (376 MHz, CDCl3) δ -116.97 (d, J = 15.4 Hz, 1F); IR v (neat, cm-1):
3046, 2963, 2232, 1649, 1484, 1260, 1153, 917, 880; HRMS (ESI-TOF, m/z): calcd. For C10H5FN2H [M+H]+: 173.0510, found:
173.0510.
(E)-2-(2-cyano-2-fluorovinyl)benzonitrile (2g). Reaction temperature: rt; reaction time: 1 h; petroleum ether/ ethylacetate = 50:1;
TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 87% yield (44.8 mg, 0.26 mmol); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J =
8.0 Hz, 1H), 7.76 (dd, J = 7.6, 0.8 Hz, 1H), 7.71 (td, J = 8.0, 1.2 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.42 (d, J = 14.8 Hz, 1H); 13C{1H}
NMR (101 MHz, CDCl3) δ 133.7, 133.7 (d, J =249.0 Hz), 133.6, 131.7 (d, J = 7.1 Hz), 130.8 (d, J = 1.4 Hz), 127.8 (d, J = 1.8 Hz),
122.1 (d, J = 26.8 Hz), 116.6, 113.4 (d, J = 4.5 Hz), 111.6 (d, J = 46.7 Hz); 19F NMR (376 MHz, CDCl3) δ -113.79 (d, J = 14.8 Hz,
1F); IR v (neat, cm-1): 3044, 2962, 2228, 1653, 1481, 1230. 891, 760; HRMS (ESI-TOF, m/z): calcd. For C10H5FN2H [M+H]+:
173.0510, found: 173.0516.
(E)-2-fluoro-3-phenylacrylonitrile (2h).11b Reaction temperature: 60 oC; reaction time: 2 h; petroleum ether; TLC: Rf = 0.8 (PE,
UV); Colorless liquid; 73% yield (30.7 mg, 0.22 mmol); 1H NMR (400 MHz, CDCl3) δ 7.61 – 7.55 (m, 2H), 7.47 – 7.41 (m, 3H),
7.07 (d, J = 16.7 Hz, 1H).
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(E)-2-fluoro-3-(p-tolyl)acrylonitrile (2i).11a Reaction temperature: 60 C; reaction time: 12 h; petroleum ether; TLC: Rf = 0.8
(PE, UV); Colorless liquid; 61% yield (29.6 mg, 0.18 mmol); 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.2
Hz, 2H), 7.03 (d, J = 17.0 Hz, 1H), 2.39 (s, 3H).
(E)-3-(4-(tert-butyl)phenyl)-2-fluoroacrylonitrile (2j).11a Reaction temperature: 60 oC; reaction time: 12 h; petroleum ether; TLC:
Rf = 0.6 (PE, UV); Colorless liquid; 60% yield (36.6 mg, 0.18 mmol); 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.6 Hz, 2H), 7.45
(d, J = 8.6 Hz, 2H), 7.04 (d, J = 16.8 Hz, 1H), 1.33 (s, 9H).
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(E)-3-([1,1'-biphenyl]-4-yl)-2-fluoroacrylonitrile (2k).11a Reaction temperature: 60 C; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.6 (PE / EA = 10:1, UV); yellow solid; 78% yield (52.2 mg, 0.23 mmol); 1H NMR (400 MHz, CDCl3)
δ 7.67 (s, 4H), 7.61 (d, J = 8.4, 2H), 7.49–7.45 (m, 2H), 7.41–7.37(m, 1H), 7.10 (d, J = 16.8 Hz, 1H).
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(E)-2-fluoro-3-(4-(methylthio)phenyl)acrylonitrile (2l).11a Reaction temperature: 60 C; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.6 (PE / EA = 10:1, UV); light yellow liquid; 80% yield (46.4 mg, 0.24 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 16.9 Hz, 1H), 2.51 (s, 3H).
(E)-2-fluoro-3-(naphthalen-2-yl)acrylonitrile (2m).20 Reaction temperature: rt; reaction time: 8 h; petroleum ether/ ethylacetate
= 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); White solid; 86% yield (50.9 mg, 0.26 mmol); 1H NMR (400 MHz, CDCl3) δ 8.01 (s,
1H), 7.93 – 7.83 (m, 3H), 7.74 (d, J = 8.4 Hz, 1H), 7.60 – 7.51 (m, 2H), 7.22 (d, J = 16.8 Hz, 1H).
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(E)-3-(3,5-dichlorophenyl)-2-fluoroacrylonitrile (2n). Reaction temperature: rt; reaction time: 1 h; petroleum ether/ ethylacetate
= 100:1; TLC: Rf = 0.6 (PE, UV); Colorless liquid; 90% yield (58.3 mg, 0.27 mmol); 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 1.6
Hz, 2H), 7.43 (t, J = 1.6 Hz, 1H), 6.95 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 136.1, 132.7 (d, J = 244.8 Hz), 131.2
(d, J = 7.1 Hz), 130.6 (d, J = 1.8 Hz), 126.7 (d, J = 3.2 Hz), 123.6 (d, J = 26.0 Hz), 111.7 (d, J = 46.7 Hz); 19F NMR (376 MHz,
CDCl3) δ -116.93 (d, J = 15.5 Hz, 1F); IR v (neat, cm-1): 2960, 2925, 2230, 1651, 1561, 1289, 1152, 814, 667; HRMS (ESI-TOF,
m/z): calcd. For C9H4Cl2FNH [M+H]+: 215.9778, found: 215.9780.
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(E)-3-(2-bromo-5-(trifluoromethyl)phenyl)-2-fluoroacrylonitrile (2o). Reaction temperature: rt; reaction time: 1 h; petroleum
ether/ ethylacetate = 100:1; TLC: Rf = 0.6 (PE, UV); Colorless liquid; 86% yield (76.2 mg, 0.26 mmol); 1H NMR (400 MHz, CDCl3)
δ 7.93 (d, J = 2.0 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.56 (dd, J = 8.4, 1.8 Hz, 1H), 7.32 (d, J = 14.4 Hz, 1H); 13C{1H} NMR (101
MHz, CDCl3) δ 134.2, 133.8 (d, J = 248.8 Hz), 131.0 (q, J = 33.6 Hz), 130.2 (d, J = 7.6 Hz), 128.6 (dd, J = 4.5, 1.5 Hz), 128.3 (q, J
= 3.7 Hz), 126.2 (qd, J = 3.8, 1.6 Hz), 124.2 (d, J = 26.9 Hz), 123.4 (q, J = 273.7 Hz), 111.2 (d, J = 46.6 Hz); 19F NMR (376 MHz,
CDCl3) δ -62.97 (s, 3F), -114.97 (d, J = 14.2 Hz, 1F); IR v (neat, cm-1): 3053, 2925, 2232, 1654, 1469, 1337, 1215, 1084, 830; HRMS
(ESI-TOF, m/z): calcd. For C10H4BrF4NH [M+H]+: 293.9536, found: 293.9540.
(E)-3-(2-bromo-5-methoxyphenyl)-2-fluoroacrylonitrile (2p). Reaction temperature: rt; reaction time: 4 h; petroleum ether/
ethylacetate = 100:1; TLC: Rf = 0.6 (PE, UV); Colorless liquid; 92% yield (70.7mg, 0.28 mmol); 1H NMR (400 MHz, CDCl3) δ 7.52
(d, J = 8.8 Hz, 1H), 7.33 (d, J = 15.2 Hz, 1H), 7.27 (d, J = 2.8 Hz, 1H), 6.86 (dd, J = 8.8, 3.2 Hz, 1H), 3.83 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 159.3, 134.1, 132.8 (d, J = 243.6 Hz), 129.5 (d, J = 7.1 Hz), 125.6 (d, J = 26.2 Hz), 118.5 (d, J = 1.1 Hz), 115.2
(d, J = 4.7 Hz), 114.0 (d, J = 1.3 Hz), 112.0 (d, J = 47.0 Hz), 55.8, 19F NMR (376 MHz, CDCl3) δ -118.08 (d, J = 15.4 Hz, 1F); IR v
(neat, cm-1): 3049, 2939, 2229, 1651, 1592, 1466, 1243, 846, 657; HRMS (ESI-TOF, m/z): calcd. For C10H7BrFNOH [M+H]+:
255.9768, found: 255.9770.
(2E,2'E)-3,3'-(1,4-phenylene)bis(2-fluoroacrylonitrile) (2q). Reaction temperature: 60 oC; reaction time: 4 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); White solid (mp: 120 - 121 oC); 67% yield (43.4 mg, 0.20 mmol); 1H NMR
(400 MHz, CDCl3) δ 7.66 (s, 4H), 7.07 (d, J = 16.8 Hz, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 132.1 (d, J = 242.5 Hz), 130.4 (dd,
J = 5.9, 3.0 Hz), 129.3 (d, J = 2.3 Hz), 125.0 (d, J = 24.2 Hz), 112.3 (d, J = 46.8 Hz); 19F NMR (376 MHz, CDCl3) δ -118.95 (d, J =
16.4 Hz, 2F); IR v (neat, cm-1): 3046, 2957, 2225, 1697, 1489, 1295, 1234, 970, 878; HRMS (ESI-TOF, m/z): calcd. For C12H6F2N2Na
[M+Na]+: 239.0391, found: 239.0397.
2-fluoro-3,3-diphenylacrylonitrile (2r).11a Reaction temperature: 60 oC; reaction time: 3 h; petroleum ether/ ethylacetate = 50:1;
TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 94% yield (62.9 mg, 0.28 mmol); 1H NMR (400 MHz, CDCl3) δ 7.50 – 7.42
(m, 3H), 7.42 – 7.35 (m, 5H), 7.34-7.31 (m, 2H).
(E)-methyl 4-(1-cyano-1-fluoroprop-1-en-2-yl)benzoate (2s). Reaction temperature: 40 oC; reaction time: 6 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 92% yield (60.5 mg, 0.28 mmol); 1H NMR (400 MHz,
CDCl3) δ 8.10 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 3.94 (s, 3H), 2.24 (d, J = 4.4 Hz, 3H, E), 2.32 (d, J = 4.4 Hz, 3H, Z), (
E/Z = 7:1 ); 13C{1H} NMR (101 MHz, CDCl3) δ 166.4, 139.0 (d, J = 3.9 Hz), 135.7 (d, J = 16.9 Hz), 131.5 (E), 130.0 (Z), 130.3 (d,
J = 3.6 Hz), 130.3 (d, J = 242.3 Hz), 128.2 (d, J = 5.5 Hz, Z), 127.9 (d, J = 3.0 Hz, E), 112.3 (d, J = 46.6 Hz), 52.5, 18.2 (Z), 16.7 (d,
J = 3.2 Hz, E); 19F NMR (376 MHz, CDCl3) δ -121.70 (q, J = 4.3 Hz,1F, E), -124.59 (q, J = 3.8 Hz, 1F, Z), ( E/Z = 7:1 ); IR v (neat,
cm-1): 2956, 2918, 2224, 1728, 1610, 1436, 1277, 800, 727; HRMS (ESI-TOF, m/z): calcd. For C12H10FNO2H [M+H]+: 220.0768,
found: 220.0770.
(E)-4-(1-cyano-1-fluoroprop-1-en-2-yl)benzonitrile (2t). Reaction temperature: rt; reaction time: 5 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 94% yield (52.5 mg, 0.28 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 2.32 (d, J = 4.2 Hz, 3H, Z), 2.24 (d, J = 4.2 Hz, 3H, E), ( E/Z = 7:1 );
13C{1H} NMR (101 MHz, CDCl3) δ 139.1 (d, J = 4.1 Hz), 135.0 (d, J = 18.2 Hz), 132.9 (E), 132.51 (Z), 130.5 (d, J = 243.4 Hz),
128.9 (d, J = 5.6 Hz, Z), 128.6 (d, J = 3.0 Hz, E), 118.1, 113.8, 112.0 (d, J = 46.5 Hz), 18.0 (Z), 16.6 (d, J = 3.1 Hz, E); 19F NMR
(376 MHz, CDCl3) δ -120.20 (q, J = 4.5 Hz, 1F, E); -123.16 (q, J = 3.8 Hz, 1F, Z), ( E/Z = 7:1 ); IR v (neat, cm-1): 2959, 2924, 2229,
1654, 1504, 1300, 1071, 870, 730; HRMS (ESI-TOF, m/z): calcd. For C11H7FN2H [M+H]+: 187.0666, found: 187.0668.
(E)-2-fluoro-3-(3-nitrophenyl)but-2-enenitrile (2u). Reaction temperature: rt; reaction time: 12 h; petroleum ether/ ethylacetate
= 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 92% yield (56.9 mg, 0.28 mmol); 1H NMR (400 MHz, CDCl3) δ 8.35
– 8.27 (m, 2H), 7.78 (d, J = 7.8 Hz, 1H), 7.65 (m, 1H), 2.28 (d, J = 4.4 Hz, 3H, E), 2.37 (d, J = 4.0 Hz, 3H, Z), ( E/Z = 7:1 ); 13C{1H}
NMR (101 MHz, CDCl3) δ 148.6, 136.2 (d, J = 4.3 Hz), 134.6 (d, J = 18.1 Hz), 133.8 (d, J = 2.6 Hz), 130.7 (d, J = 244.3 Hz), 130.4,
124.7 (E), 124.5 (Z), 123.1 (d, J = 5.4 Hz, Z),123.0 (d, J = 3.5 Hz, E), 111.9 (d, J = 46.4 Hz), 18.1 (Z), 16.8 (d, J = 3.0 Hz, E); 19
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NMR (376 MHz, CDCl3) δ -120.41 (q, J = 4.2 Hz, 1F, E), -123.53 (q, J = 4.2 Hz, 1F, Z), ( E/Z = 7:1 ); IR v (neat, cm-1): 3086, 2926,
2225, 1654, 1531, 1210, 901, 806, 738; HRMS (ESI-TOF, m/z): calcd. For C10H7FN2O2H [M+H]+: 207.0564, found: 207.0560.
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(E)-2-fluoro-3-(4-(trifluoromethyl)phenyl)pent-2-enenitrile (2v). Reaction temperature: 60 C; reaction time: 12 h; petroleum
ether/ ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 10:1, UV); Colorless liquid; 75% yield (54.7 mg, 0.22 mmol); 1H NMR (400
MHz, CDCl3) δ 7.71 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 2.68 (qd, J = 7.6, 3.4 Hz, 2H), 1.07 (t, J = 7.6 Hz, 3H, Z), 1.02 (t,
J = 7.6 Hz, 3H, E), ( E/Z = 8:1 ); 13C{1H} NMR (151 MHz, CDCl3) δ 141.2 (d, J = 16.2 Hz), 137.1 (d, J = 3.9 Hz), 131.9 (q, J = 32.9
Hz), 130.0 (d, J = 242.5 Hz), 128.8 (d, J = 2.9 Hz), 126.1 (q, J = 3.7 Hz, E), 125.9 (q, J = 3.7 Hz, Z), 123.8 (q, J = 272.3 Hz), 112.1
(d, J = 47.0 Hz), 25.6 (Z), 24.0 (d, J = 1.9 Hz, E), 12.9 (d, J = 3.4 Hz, Z), 11.9 (d, J = 2.2 Hz, E); 19F NMR (376 MHz, CDCl3) δ -
62.94 (s, 3F), -123.47 (t, 3.8Hz, 1F, E), -126.38 (Z) ( E/Z = 8:1 ); IR v (neat, cm-1): 2962, 2927, 2228, 1540, 1260, 1098, 947, 842,
800; HRMS (ESI-TOF, m/z): calcd. For C12H9F4NH [M+H]+: 244.0744, found: 244.0750.
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(E)-2-fluoro-3-phenyl-3-(p-tolylthio)acrylonitrile (2w). Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.6 (PE / EA = 10:1, UV); Light yellow liquid; 87% yield (70.3 mg, 0.26 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.34 – 7.21 (m, 5H), 7.13 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.2 Hz, 2H), 2.37 (s, 3H, Z), 2.23 (s, 3H, E), ( E/Z = 9:1 ); 13C{1H}
NMR (101 MHz, CDCl3) δ 139.5, 134.3, 131.6 (Z), 130.1 (Z) 131.0 (d, J = 26.4 Hz), 130.4 (d, J = 0.8 Hz), 130.2 (E), 130.0 (d, J =
3.0 Hz), 129.9 (E), 128.7, 127.7 (d, J = 242.5 Hz) 125.4 (d, J = 2.2 Hz), 112.4 (d, J = 45.3 Hz), 21.2; 19F NMR (376 MHz, CDCl3) δ
-117.82 (s, 1F, E); -112.02 (s, 1F, Z), ( E/Z = 9:1 ); IR v (neat, cm-1): 3024, 2923, 2220, 1597, 1459, 1492, 1207, 808, 756; HRMS
(ESI-TOF, m/z): calcd. For C16H12FNSH [M+H]+: 270.0747, found: 270.0750.
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General procedure for the synthesis of product 3. An oven-dried 10 mL Schlenk tube was charged with Cs2CO3 (0.02 mmol,
6.5 mg), TMSCF3 (0.5 mmol), 1 (0.2 mmol), and then anhydrous DMF (1.0 mL) was added through syringe. After stirring at room
temperature for 12 hours, the solvent was removed in vacuo. Purification of the residue by silica gel column chromatography afforded
the desired product 3.
(perfluoroprop-1-ene-1,1-diyl)dibenzene (3a).3b Reaction temperature: rt; reaction time: 12 h; petroleum ether; TLC: Rf = 0.5
(PE , UV); Colorless liquid; 74% yield (39.5 mg, 0.15 mmol); 1H NMR (400 MHz, CDCl3) δ 7.48 – 7.17 (m, 10H).
(Z)-methyl 4-(3,4,4,4-tetrafluorobut-2-en-2-yl)benzoate (3b). Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 51% yield (26.7 mg, 0.10 mmol); 1H NMR (400 MHz,
CDCl3) δ 8.07 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 3.93 (s, 3H), 2.18 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 166.6 (s),
142.3 (dq, J = 255.0, 38.3 Hz), 140.7 (s), 130.1 (d, J = 60.7 Hz), 129.9 (s), 128.0 (d, J = 3.8 Hz), 122.5 (dq, J = 9.8, 2.6 Hz), 119.9
(qd, J = 273.2, 42.1 Hz), 52.4 (s), 16.1 (m); 19F NMR (376 MHz, CDCl3) δ -64.94 – -65.07 (m), -128.06 – -128.08 (m) IR v (neat,
cm-1): 2957, 1728, 1611, 1340, 1311, 1276, 1137, 773,706; HRMS (ESI-TOF, m/z): calcd. For C12H10F4O2H [M+H]+: 263.0690,
found: 263.0698.
(Z)-4-(3,4,4,4-tetrafluorobut-2-en-2-yl)benzonitrile (3c). Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 70% yield (32.1 mg, 0.14 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.70 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H), 2.18 (m, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 142.7 (dq, J = 260.2,
38.8 Hz), 140.8 (s), 132.5 (d, J = 1.3 Hz), 128.8 (d, J = 3.5 Hz), 121.7 (dq, J = 3.5, 2.6 Hz), 119.4 (dq, J = 274.4, 42.1 Hz), 118.5 (d,
J = 4.7 Hz), 112.6 (d, J = 3.2 Hz), 15.9 (s); 19F NMR (376 MHz, CDCl3) δ -65.08 – -65.21 (m), -126.92 – -126.99 (m) IR v (neat, cm-
1): 2961, 2231, 1342, 1273, 1138, 1030, 877, 829, 623; HRMS (ESI-TOF, m/z): calcd. For C11H7F4NH [M+H]+: 230.0587, found:
230.0580.
(Z)-1-nitro-3-(3,4,4,4-tetrafluorobut-2-en-2-yl)benzene (3d). Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 80% yield (39.9 mg, 0.16 mmol); 1H NMR (400 MHz,
CDCl3) δ 8.24 (s, 1H), 8.23 (d, J = 7.3 Hz, 1H), 7.70 (d, J = 7.5 Hz, 1H), 7.60 (t, J = 8.2 Hz, 1H), 2.26 (m, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 148.5 (s), 143.0 (dq, J = 256.8, 38.4 Hz), 137.7 (s), 134.1 (d, J = 4.3 Hz), 129.7 (s), 123.6 (s), 123.0 (d, J = 3.7 Hz),
121.2 (dq, J = 5.5, 2.4 Hz), 119.7 (dq, J = 273.3, 41.8 Hz), 16.0 (qd, J = 2.7, 1.0 Hz); 19F NMR (376 MHz, CDCl3) δ -65.05 – -65.18
(m), -127.13 – -127.16 (m) IR v (neat, cm-1): 2962, 1536, 1304, 1179, 1140, 1030, 808, 739, 691; HRMS (ESI-TOF, m/z): calcd. For
C10H7F4NO2H [M+H]+: 250.0486, found: 250.0490.
(E)-2,3,3,3-tetrafluoro-1-(naphthalen-2-yl)prop-1-en-1-yl benzoate (3e). Reaction temperature: rt; reaction time: 12 h; petro-
leum ether/ ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 81% yield (49.2 mg, 0.16 mmol); 1H NMR
(400 MHz, CDCl3) δ 8.19 (d, J = 7.2 Hz, 2H), 8.13 (s, 1H), 7.89 (d, J = 8.7 Hz, 1H), 7.85 (dd, J = 7.8, 4.7 Hz, 2H), 7.70 (t, J = 7.9
Hz, 2H), 7.55 (t, J = 8.3 Hz, 4H); 13C{1H} NMR (101 MHz, CDCl3) δ 164.1 (s), 141.8 (dq, J = 258.7, 38.6 Hz), 134.5 (s), 134.3 (s),
134.1 (s), 132.9 (s), 130.6 (s), 129.0 (s), 129.0 (s), 128.8 (s), 128.4 (s), 127.9 (s), 127.8 (s), 127.0 (s), 123.6 (d, J = 7.1 Hz), 123.9 (dq,
J = 7.2, 2.5 Hz), 119.4 (dq, J = 273.9, 37.3 Hz); 19F NMR (376 MHz, CDCl3) δ -66.99 (d, J = 9.4 Hz), -150.88 (q, J = 9.3 Hz) IR v
(neat, cm-1): 2926, 1755, 1600, 1363, 1200, 1153, 1019, 852, 711; HRMS (ESI-TOF, m/z): calcd. For C20H16F4NO2 [M+NH4]+:
378.1112, found: 378.1113.
(E)-2,3,3,3-tetrafluoro-1-phenylprop-1-en-1-yl 4-methyl benzenesulfonate (3f). Reaction temperature: rt; reaction time: 12 h;
petroleum ether/ ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 87% yield (62.8 mg, 0.17 mmol); 1H
NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.1 Hz, 2H), 7.34 (t, J = 8.7 Hz, 3H), 7.25 (d, J = 10.9 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 2.39
(s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 146.0 (d, J = 2.7 Hz), 143.0 (dq, J = 114.6, 38.7 Hz), 132.8 (d, J = 6.5 Hz), 130.7 (s),
129.8 (d, J = 1.1 Hz), 128.6 (s), 128.5 (s), 128.4 (s), 128.2 (s), 128.1 (qd, J = 4.3, 1.5Hz), 118.8 (qd, J = 273.5, 37.3 Hz), 21.8 (d, J =
3.6 Hz); 19F NMR (376 MHz, CDCl3) δ -66.64 (d, J = 9.9 Hz), -149.28 (q, J = 9.8 Hz) ; IR v (neat, cm-1): 2962, 1693, 1391, 1148,
1065, 917, 813, 763, 669; HRMS (ESI-TOF, m/z): calcd. For C16H16F4NO3S [M+NH4]+: 378.0782, found: 378.0783.
(Z)-methyl 4-(2,3,3,3-tetrafluoroprop-1-en-1-yl)benzoate (3g).14a Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 43% yield (21.3 mg, 0.09 mmol); 1H NMR (400 MHz,
CDCl3) δ 8.07 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 35.0 Hz, 1H), 3.93 (s, 3H).
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(Z)-4-(2,3,3,3-tetrafluoroprop-1-en-1-yl)benzonitrile (3h).14a Reaction temperature: rt; reaction time: 12 h; petroleum ether/
ethylacetate = 50:1; TLC: Rf = 0.5 (PE / EA = 20:1, UV); Colorless liquid; 44% yield (19.2 mg, 0.09 mmol); 1H NMR (400 MHz,
CDCl3) δ 7.71 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H), 6.41 (d, J = 34.3 Hz, 1H).
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ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website.
Reaction optimization for trifluoromethylation, NMR spectra for the products (PDF)
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Corresponding Author
qinghaideng@shnu.edu.cn
ORCID
Qing-Hai Deng: 0000-0001-7793-1434
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support from the Program of the Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning,
Shanghai Engineering Research Center of Green Energy Chemical Engineering (18DZ2254200), the National Natural Science Foundation
of China (no. 21402119, 21772122), and Shanghai Rising-Star Program (no. 16QA1403100) is greatly appreciated.
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