Difluorocarbene-based trifluoromethylthiolation of terminal alkynes

Article abstract of DOI:10.1016/j.jfluchem.2019.109437

A large number of trifluoromethylthiolation methods have been developed, but a trifluoromethylthiolation reagent usually has to be used in these methods. Herein we describe a difluorocarbene-based trifluoromethylthiolation of terminal alkynes to construct a Csp[sbnd]SCF₃ bond catalysed by a copper complex. Ph₃P⁺CF₂CO₂^?/S₈/F^? was used as a reagent system to form the CF₃S^? anion, and the sequential formation of CF₂[dbnd]S, F[sbnd]CF₂S and C[sbnd]SCF₃ bonds was achieved in a one-step process.

Full text of DOI:10.1016/j.jfluchem.2019.109437

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Difluorocarbene-based trifluoromethylthiolation of terminal alkynes
Guowen He, Yan-Hua Jiang, Xuan Xiao, Jin-Hong Lin, Xing Zheng,
Ruo-Bing Du, Yu-Cai Cao, Ji-Chang Xiao
PII:
S0022-1139(19)30429-4
DOI:
https://doi.org/10.1016/j.jfluchem.2019.109437
FLUOR 109437
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
19 October 2019
3 December 2019
3 December 2019
Please cite this article as: He G, Jiang Y-Hua, Xiao X, Lin J-Hong, Zheng X, Du R-Bing, Cao
Y-Cai, Xiao J-Chang, Difluorocarbene-based trifluoromethylthiolation of terminal alkynes,
Journal of Fluorine Chemistry (2019), doi: https://doi.org/10.1016/j.jfluchem.2019.109437
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Difluorocarbene-based trifluoromethylthiolation of terminal alkynes
Guowen He,a‡ Yan-Hua Jiang,c‡ Xuan Xiao,bc‡ Jin-Hong Lin, * Xing Zheng, * Ruo-Bing Du,
c
b
c
Yu-Cai Cao, Ji-Chang Xiaoc*
d
aHunan Provincial Key Lab of Dark Tea and Jin-hua, School of Materials and Chemical
Engineering, Hunan City University, Yiyang 413000, China.
bInstitute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for
Molecular Target New Drug Study, University of South China, 28 Western Changsheng Road,
Hengyang, Hunan, 421001, China. Email: zhengxing5018@yahoo.com.
cKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032.
Email: jlin@sioc.ac.cn; jchxiao@sioc.ac.cn.
dState key Laboratory of polyolefins and Catalysis, Shanghai Key Laboratory of Catalysis
Technology for Polyolefins, Shanghai Research Institute of Chemical Industry Co. Ltd.
‡
These authors contributed equally to this work.
Graphical Abstract
Highlights



A sequential construction of CF
one-step reaction.
2
=S, F-CF
2
S and C-SCF bonds was achieved in a
3
P+CF
-
make this Csp-H bond
The easy accessibility of Ph
trifluoromethylthiolation protocol attractive.
This protocol may find applications in 18F-trifluoromethylthiolation since an
external fluoride anion is involved for the construction of the CF S unit.
3
2
CO
2
3

Abstract: A large number of trifluoromethylthiolation methods have been developed,
but a trifluoromethylthiolation reagent usually has to be used in these methods. Herein
we describe a difluorocarbene-based trifluoromethylthiolation of terminal alkynes to
P+CF
CO -
/S
/F was
-
construct a Csp-SCF
used as a reagent system to form the CF
CF =S, F-CF S and C-SCF bonds was achieved in a one-step process.
3
bond catalysed by a copper complex. Ph
3
2
2
8
S- anion, and the sequential formation of
3
2
2
3
Keywords: Trifluoromethylthiolation, Difluorocarbene, Terminal alkynes, Copper, Fluorine.
1
. Introduction
Due to its strong electron-withdrawing (Hammett constants σ
p
= 0.50, σ = 0.40) and high
m
lipophilicity (Hansch lipophilicity parameter π = 1.44) effects [1-3], the trifluoromethylthio group
CF S) has received particular attention in the design of pharmaceuticals and agrochemicals [4-6].
Many CF S-containing biologically active molecules have emerged recently, such as Toltrazuril,
Tiflorex and Cefazaflur [6]. Therefore, significant efforts have been devoted to the development
of efficient methods for the incorporation of a CF S group into organic molecules [6-16]. A large
number of trifluoromethylthiolation reagents have been developed, including nucleophilic
(
3
3
3
+
-
reagents, such as AgSCF
reagents, such as N-SCF
3
[17], CuSCF
3
[18-23] and [R
4
N] SCF
3
[24, 25], and electrophilic
CF type [35] reagents.
3
type [26-32], O-SCF
3
type [33, 34], and C-SO
2
3
The emergence of the general trifluoromethylthiolation reagents has allowed the development of a
variety of trifluoromethylthiolation approaches, including nucleophilic [36-39], electrophilic
[
40-43] and radical [44-48] reactions, by which various C-SCF
constructed.
The formation of a Csp-SCF
terminal alkynes. Qing described an oxidative trifluoromethylthiolation with a nucleophilic
reagent, TMSCF /S system [49] or AgSCF [50] in the presence of an oxidant, to afford
CF S-alkynes in moderate to high yields (Scheme 1, eq 1). Billard [40, 51, 52], Rueping [29] and
3
bond could be effectively
3
bond was usually achieved by trifluoromethylthiolation of
3
8
3
3
Shen [31, 33, 53] independently disclosed the trifluoromethylthiolation of terminal alkynes with
electrophilic reagents (eq 1). The conversions were quite efficient, but suffered from strong basic
reaction conditions or the need of tedious procedures to prepare the “CF
alkynes, including alkynyl silanes [54], alkynyl acids [55], alkynyliodonium tosylates [56] and
alkynyl bromides [57], could also be converted into CF S-alkynes by trifluoromethylthiolation
3
S” reagents. Other
3
transformation (eq 2). Obviously, the need for prefunctionalization of the substrates may limit
their synthetic utility. Therefore, the development of convenient protocols for the formation of a

Csp-SCF
3
bond is desirable.
Scheme 1. The formation of C-SCF bond by trifluoromethylthiolation
3
Difluorocarbene has proved to be a versatile intermediate for the incorporation of CF
2
unit into
P+CF
CO
-
[60, 61], and
molecules [58, 59]. We recently developed a difluorocarbene reagent, Ph
3
2
2
found that difluorocarbene could react with a suitable sulfur source to generate thiocarbonyl
fluoride (CF =S) [62-64]. CF
=S is an electrophilic species and could be readily trapped by F-
anion to provide CF
S- anion. This process was developed into a synthetic tool to enable
18F-trifluoromethylthioaltion
of alkyl electrophiles [62, 63] and
2
2
3
dehydroxy-trifluoromethylthiolation of alcohols [65]. On the basis of these
trifluoromethylthiolation conversions, we have now investigated the difluorocarbene-based
trifluoromethylthiolation of terminal alkynes catalyzed by a copper complex (Scheme 1, eq 3). A
sequential formation of CF
2
=S, F-CF
2
S and C-SCF bonds was achieved in a one-step
3
process. Ph , which was used as the difluorocarbene source in the transformations,
3
P+CF CO -
2
2
could be easily prepared by a one-step reaction and purified by a simple washing procedure, and
therefore the operationally convenient trifluoromethylthiolation protocol would be quite attractive.
2
. Results and discussion
Although DMF was found to be a suitable solvent in the oxidative trifluoromethylthiolation
[
49], no desired product was observed in our initial attempts at the trifluoromethylthiolation of
P+CF
CO -
/S
8
/F system (Table 1, entry 1). To our delight, a 3% yield was
-
alkyne 1a with the Ph
3
2
2
obtained by using ethyl acetate as the solvent (entry 2), which encouraged us to further screen
other solvents. After the identification of the suitable solvent, THF (entry 4), we then examined

various fluoride sources (entries 4-7). The lower solubility of KF did not lead to the decrease in
the yield. Instead, the yield was increased to 26% (entry 5 vs entry 4). Interestingly, decreasing the
loadings of the copper complex gave higher yields (entries 8-9 vs entry 5), but no expected
product was generated without using the copper complex (entry 11), indicating that the copper
complex is essential for this conversion. A brief survey of the copper sources revealed that CuI
was a superior choice (entry 9 vs entries 12-14). The use of a tertiary amine as the base afforded
moderate yields (entries 9 and 15), but the desired transformation was completely suppressed
when using a secondary amine (entry 16). The yield was increased by increasing the loadings of
Ph
3
P+CF
2
CO -
2
and S
8
(entries 17-18). A high yield was obtained by replacing the ligand L1 with
L4 (entry 21).
Table 1. The optimization of the reaction contidions a
[
Cu]
Ligand
(mol %)
L1 (100)
L1 (100)
L1 (100)
L1 (100)
L1 (100)
L1 (100)
L1 (100)
L1 (50)
L1 (20)
L1 (10)
-
Yield
(%)c
0
Entry
F-
Base
Molar ratiob
(
mol %)
1d
2e
3f
4g
5
CsF
CsF
CsF
CsF
KF
CuI (100)
CuI (100)
CuI (100)
CuI (100)
CuI (100)
CuI (100)
CuI (100)
CuI (50)
CuI (20)
CuI (10)
-
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
N
N
N
N
N
N
N
N
N
N
N
N
N
N
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
1 : 2.5 : 0.9
3
8
14
26
6
NaF
TBAT
KF
13
7
10
8
31
9
KF
44
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
KF
30
KF
0
KF
CuBr (20)
CuCl (20)
CuOTf (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
L1 (20)
L1 (20)
L1 (20)
trace
trace
trace
46
KF
KF
KF
L1 (20) TMEDA 1 : 2.5 : 0.9
KF
L1 (20)
2
Et NH
1 : 2.5 : 0.9
1 : 3 : 1.1
1 : 4 : 1.5
1 : 4 : 1.5
1 : 4 : 1.5
1 : 4 : 1.5
0
KF
L1 (20) TMEDA
L1 (20) TMEDA
L2 (20) TMEDA
L3 (20) TMEDA
L4 (20) TMEDA
57
KF
73
1
2
2
9h
0h
1h
KF
82
KF
77
KF
84

aReaction conditions: substrate 1a (0.2 mmol), 2, S
, F (1.2 mmol), copper source [Cu], ligand, base (0.4 mmol) in
-
8
o
THF (2 mL) at 60 C for 2 h under a N
2
atmosphere; TBAT = n-tetrabutylammonium triphenyldifluorosilicate;
b
; cDetermined by 19F NMR spectroscopy;
8
TMEDA = N,N,N′,N′-tetramethylethylenediamine; Molar ratio of 1a:2:S
d
e
f
g
DMF was used as the solvent; EtOAc was used as the solvent; 1,4-dioxane was used as the solvent; THF was
h
used as the solvent; The reaction time was 3 h.
With the optimal reaction conditions in hand (Table 1, entry 21), we then investigated the
substrate scope of the difluorocarbene-based trifluoromethylthiolation of terminal alkynes. As
shown in Scheme 2, a wide range of terminal alkynes could be converted smoothly into the
desired products in moderate to good yields. The examination of electronic effects showed that
neither electron-donating nor -withdrawing groups had obvious side effects on the conversion of
phenyl alkynes (3a-3l). Pyridine heterocylces could be tolerated under these conditions (3m).
Besides phenyl alkynes, alkyl alkynes were also found to be reactive towards this conversion, but
lower yields were obtained (3n-3o).

Scheme 2 Difluorocarbene-based trifluoromethylthiolation of terminal alkynes. Isolated yields.
Reaction conditions: substrate 1 (0.4 mmol), 2 (4 equiv), S
8
(1.5 equiv), KF (6 equiv), CuI (0.2
o
equiv), L4 (0.2 equiv), TMEDA (2 equiv) in THF (3 mL) at 60 C for 3 h under a N
2
atmosphere.
On the basis of the above results and our previous observations on difluorocarbene-based
trifluoromethylthiolation [62, 63, 65], we propose that the mechanism shown in Scheme 3 is
S- anion generated from Ph
P+CF
-
via :CF
followed by CF =S coordinates
plausible. The CF
3
3
2
CO
2
2
2
I
to the copper center to give Cu SCF
3
complex. The coordination of the terminal alkynes to
I
Cu SCF
3
(intermediate A) increases the acidity of the terminal proton and thus a deprotonation
) may
would readily occur to provide copper acetylide (intermediate B). Elemental sulfur (S
8
I
III
oxidize Cu to Cu (intermediate C), and the subsequent reductive elimination delivers the final
products and releases the catalyst.

Scheme 3 The plausible reaction mechanism
3
. Conclusions
In summary, we have described the difluorocarbene-based trifluoromethylthiolation of
-
terminal alkynes with the Ph
and C-SCF
protocol is attractive as Ph
application in 18F-trifluoromethylthiolation since an external fluoride anion is involved for the
construction of the CF S moiety.
3
P+CF
2
CO
2
-/S
8
/F system. A sequential formation of CF
2
=S, F-CF S
2
3
bonds was achieved in a one-step transformation. The trifluoromethylthiolation
P+CF CO -
is easily available and shelf-stable. This process may find
3
2
2
3
4
. Experimental section
4.1 General remark
1
13
19
H, C and F NMR spectra were detected on a 400 MHz or 300 MHz NMR spectrometer.
Data for H NMR, 13C NMR and 19F NMR were recorded as follows: chemical shift (δ, ppm),
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, q = quartet, coupling constant (s) in
Hz). Mass spectra were obtained on GC-MS (EI). High resolution mass data were recorded on a
high resolution mass spectrometer in the EI mode.
1
4.2 General procedure for trifluoromethylthiolation:
P+CF
CO (570.1 mg, 1.6
-
In to a 10 mL sealed tube were added alkynes 1 (0.4 mmol), Ph
3
2
2
mmol), S
8
(153.9 mg, 0.6 mmol), CuI (15.2 mg, 0.08mmol), 4,4’-di-tert-butyl-2,2’-bipyridine
(
21.5 mg, 0.08 mmol), KF (139.4 mg, 2.4 mmol), TMEDA (92.9 mg, 0.8 mmol) and anhydrous
THF (4 mL) under a N atmosphere. The tube was sealed and the resulting mixture was stirred at
2
o
6
0 C for 3 h. After being cooled to room temperature, the mixture was filtered through a plug of
Celite, and the solid was washed with DCM. The combined organic phase was washed with brine
10 mL × 3) and water (10 mL × 3) and dried with Na SO . The solvent was removed by
(
2
4
concentration under vacuum, and the residue was subjected to flash column chromatography to
give the final products.
4.3 Characterization of the products:

1
(
3a) [49]: White solid, 85%. H NMR (400 MHz, CDCl
3
) δ 7.62 - 7.57 (m, 6H), 7.47 (t, J =
.4 Hz, 2H), 7.43 - 7.37 (m, 1H). F NMR (376 MHz, CDCl
) δ -43.6 (s, 3F). 13C NMR (101
MHz, CDCl ) δ 142.6 (s), 140.0 (s), 132.7 (s), 129.0 (s), 128.2 (q, J = 312.5 Hz), 128.0 (s), 127.2
19
7
3
3
(
[
s), 127.1 (s), 120.4 (s), 101.3 (s), 67.3 (q, J = 4.1 Hz). GC-MS (EI): Calculated for C15
H
9
F S
3
+
M] : 278.0; Found: 278.1.
1
(
3b) [49]: Colorless oil, 71%. H NMR (400 MHz, CDCl
3
) δ 7.45 (d, J = 8.6 Hz, 2H), 7.37 (d,
1
9
13
J = 8.6 Hz, 2H), 1.32 (s, 9H). F NMR (376 MHz, CDCl
CDCl
.1 Hz), 33.9 (s), 30.0 (s). GC-MS (EI): Calculated for C13
3
) δ -43.9 (s, 3F). C NMR (101 MHz,
3
) δ 152.3 (s), 131.1 (s), 127.1 (q, J = 312.5 Hz), 124.5 (s), 117.5 (s), 100.5 (s), 64.8 (q, J =
+
4
H
13
F S [M] : 258.1; Found: 258.1.
3
1
(
3c) [49]: Yellow solid, 68%. H NMR (400 MHz, CDCl
3
) δ 7.38 (d, J = 8.7 Hz, 2H), 6.60 (d,
1
9
13
J = 8.9 Hz, 2H), 2.99 (s, 6H). F NMR (376 MHz, CDCl
CDCl
3
) δ -44.7 (s, 3F). C NMR (101 MHz,
3
) δ 151.1 (s), 134.3 (s), 128.2 (q, J = 312.6 Hz), 111.5 (s), 107.8 (s), 103.2 (s), 63.9 (q, J =
+
4
.4 Hz), 40.0 (s). GC-MS (EI): Calculated for C11
H
10
F NS [M] : 245.0; Found: 245.0.
3
1
(
3d): Pale yellow oil, 81%. H NMR (400 MHz, CDCl
3
) δ 7.46 (d, J = 8.8 Hz, 2H), 7.36 (t, J
=
7.9 Hz, 2H), 7.17 (t, J = 7.5 Hz, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H). 19F
NMR (376 MHz, CDCl
3
) δ -43.9 (s, 3F). 13C NMR (101 MHz, CDCl
) δ 159.2 (s), 155.9 (s),
3
1
6
34.4 (s), 130.0 (s), 128.2 (q, J = 312.5 Hz), 124.3 (s), 119.9 (s), 118.1 (s), 115.7 (s), 101.0 (s),
+
6.0 (q, J = 4.2 Hz). HRMS (EI): Calculated for C15
H
9
OF S [M] : 294.0326; Found 294.0330. IR
3
(
neat) ν: 2962, 2176, 1588, 1504, 1489, 1281, 1246, 1165, 1104, 908, 880, 862, 837, 750, 735, 692
-
1
cm .
1
(
3e) [49]: Pale yellow oil, 80%. H NMR (400 MHz, CDCl
3
) δ 7.45 (d, J = 8.7 Hz, 2H), 6.85
19
13
(
d, J = 8.8 Hz, 2H), 3.81 (s, 3H). F NMR (376 MHz, CDCl
3
) δ -44.1 (s, 3F) C NMR (101 MHz,
3
CDCl ) δ 160.9 (s), 134.4 (s), 128.2 (q, J = 312.4 Hz), 114.1 (s), 113.5 (s), 101.5 (s), 65.2 (q, J =
+
4
.4 Hz)., 55.3 (s). GC-MS (EI): Calculated for C10
H
7
F
3
OS [M] : 232.0; Found: 232.0.
1
(
3f): Pale yellow oil, 88%. H NMR (400 MHz, CDCl ) δ 7.44 (dd, J = 7.6, 1.7 Hz, 1H), 7.34
3
(
ddd, J = 8.4, 7.6, 1.7 Hz, 1H), 6.91 (td, J = 7.5, 0.9 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 3.87 (s, 3H).
19F NMR (376 MHz, CDCl
) δ -43.9 (s, 3F). C NMR (101 MHz, CDCl
13
3
3
) δ 160.8 (s), 134.2 (s),
131.4 (s), 128.2 (q, J = 312.5 Hz), 120.5 (s), 110.9 (s), 97.9 (s), 70.2 (q, J = 4.2 Hz), 55.8 (s).
+
HRMS (EI): Calculated for C10
H
7
OF S [M] : 232.0170; Found: 232.0172. IR (neat) V: 2938, 2178,
3
-
1
1
596, 1576, 1491, 1465, 1435, 1282, 1262, 1161, 1104, 1047, 1025, 782, 752 cm .
1
(
3g) [54]: Pale yellow oil, 80%. H NMR (400 MHz, CDCl
3
) δ 7.24 (t, J = 7.9 Hz, 1H), 7.08
(
(
dt, J = 7.6, 1.1 Hz, 1H), 7.00 (dd, J = 2.3, 1.5 Hz, 1H), 6.94 (ddd, J = 8.4, 2.6, 0.9 Hz, 1H), 3.79
19
13
s, 3H). F NMR (376 MHz, CDCl
3
) δ -43.6 (s, 3F). C NMR (101 MHz, CDCl ) δ 159.4 (s),
3

1
4
29.5 (s), 128.1 (q, J = 312.5 Hz), 124.7 (s), 122.4 (s), 116.8 (s), 116.4 (s), 101.3 (s), 66.5 (q, J =
+
.4 Hz), 55.3 (s). GC-MS (EI): Calculated for C10
H
7
F
3
OS [M] : 232.0; Found: 232.0.
1
(
3h): Pale yellow oil, 87%. H NMR (400 MHz, CDCl
3
) δ 7.39 (d, J = 8.5 Hz, 1H), 6.74 (d, J
19
=
2.5 Hz, 1H), 6.69 (dd, J = 8.5, 2.6 Hz, 1H), 3.80 (s, 3H), 2.41(s, 3H). F NMR (376 MHz,
13
CDCl
3
) δ -44.4 (s, 3F). C NMR (101 MHz, CDCl ) δ 160.8 (s), 143.8 (s), 134.4 (s), 128.3 (q, J =
3
312.3 Hz), 115.2 (s), 113.6 (s), 111.4 (s), 100.6 (s), 68.4 (q, J = 4.2 Hz), 55.2 (s), 20.7 (s). HRMS
+
(
EI): Calculated for C11
H
9
OF
3
S [M] : 246.0326; Found: 246.0330. IR (neat) ν: 2961, 2840, 2166,
1605, 1564, 1497, 1466, 1315, 1299, 1283, 1260, 1232, 1157, 1103, 1042, 869, 849, 808, 756
-
1
cm .
1
(
3i) [49]: White solid, 84%. H NMR (400 MHz, CDCl
3
) δ 7.96 (s, 1H), 7.69 (d, J = 8.9 Hz,
1H), 7.67 (d, J = 8.4 Hz, 1H), 7.46 (dd, J = 8.5, 1.6 Hz, 1H), 7.16 (dd, J = 8.9, 2.5 Hz, 1H), 7.09
19
13
(
d, J = 2.5 Hz, 1H), 3.91 (s, 3H). F NMR (376 MHz, CDCl
3
) δ -43.8 (s, 3F). C NMR (101 MHz,
CDCl ) δ 158.9 (s), 134.9 (s), 132.8 (s), 129.6 (s), 128.9 (s), 128.18 (s), 128.15 (q, J = 312.7 Hz),
3
127.0 (s), 119.7 (s), 116.3 (s), 105.8 (s), 102.0 (s), 66.0 (s), 55.3 (s). GC-MS (EI): Calculated for
+
14
C H
9 3
F
OS [M] : 282.0; Found: 282.0.
1
(
3j) [49]: Pale yellow solid, 81%. H NMR (400 MHz, CDCl ) δ 8.46 (d, J = 9.1 Hz, 1H),
3
1
9
13
8
1
1
.25 - 8.01 (m, 8H). F NMR (376 MHz, CDCl
3
) δ -43.6 (s, 3F). C NMR (101 MHz, CDCl ) δ
3
32.7 (s), 132.1 (s), 130.9 (s), 130.7 (s), 123.0 (s), 128.8 (s), 128.8 (s), 128.3 (q, J = 312.7 Hz),
26.9 (s), 126.3 (s), 126.0 (s), 125.9 (s), 124.7 (s), 124.2 (s), 124.0 (s), 123.8 (s), 115.4 (s), 100.7
+
(
s), 71.5 (q, J = 4.1 Hz). GC-MS (EI): Calculated for C19
H
9
F
3
S [M] : 326.0; Found: 326.1.
o
1
(
3k): Pale yellow solid (m.p. 100 – 101 C), 78%. H NMR (400 MHz, CDCl
.3 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.66 (s, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.52 (d, J = 7.9 Hz,
H), 7.39 (t, J = 7.2 Hz, 1H), 7.36 - 7.31 (m, 1H), 3.87 (s, 2H). 19F NMR (376 MHz, CDCl
) δ
) δ 143.8 (s), 143.4 (s), 143.2 (s), 140.7 (s), 131.4 (s),
3
) δ 7.78 (d, J =
7
1
3
13
-
43.8 (s, 3F). C NMR (101 MHz, CDCl
3
1
1
28.9 (s), 128.1 (q, J = 312.5 Hz), 127.6 (s), 127.0 (s), 125.2 (s), 120.5 (s), 119.9 (s), 119.4 (s),
+
02.1 (s), 66.4 (q, J = 4.3 Hz), 36.71 (s). HRMS (EI): Calculated for C16
H
9
F S [M] : 290.0377;
3
Found: 290.0369. IR (neat) ν : 3070, 2173, 1607, 1464, 1454, 1418, 1399, 1176, 1162, 1150, 1131,
-
1
1
101, 952, 875, 839, 770, 755, 737, 593 cm .
1
(
3l) [49]: Yellow oil, 75%. H NMR (400 MHz, CDCl
3
) δ 8.00 (d, J = 8.6 Hz, 2H), 7.52 (d, J
19
=
8.6 Hz, 2H), 4.37 (q, J = 7.1 Hz, 2H), 1.38 (t, J = 7.1 Hz, 3H). F NMR (376 MHz, CDCl
3
) δ
) δ 165.7 (s), 131.6 (s), 131.1 (s), 129.5 (s), 127.9 (q, J =
12.6 Hz), 125.8 (s), 100.5 (s), 69.9 (q, J = 4.4 Hz), 61.3 (s), 14.2 (s). GC-MS (EI): Calculated for
13
-
43.3 (s, 3F). C NMR (101 MHz, CDCl
3
3
+
12
C H
9 3
F
O S [M] : 274.0; Found: 274.1.
2

1
(
3m) [29]: Pale yellow solid, 60%. H NMR (400 MHz, CDCl
3
) δ 8.92 (d, J = 1.9 Hz, 1H),
8
.30 (s, 1H), 8.09 (d, J = 8.5 Hz, 1H), 7.81 - 7.72 (m, 2H), 7.61 - 7.55 (m, 1H). 19F NMR (376
13
MHz, CDCl
3
) δ -43.2 (s, 3F). C NMR (101 MHz, CDCl ) δ 151.6 (s), 147.3 (s), 139.8 (s), 131.0
3
(
s), 129.5 (s), 128.0 (q, J = 312.6 Hz), 127.8 (s), 127.7 (s), 126.9 (s), 115.7 (s), 98.7 (s), 70.5 (q, J
+
=
4.2 Hz). GC-MS (EI): Calculated for C12
H
6
F NS [M] : 253.0; Found: 253.0.
3
1
(
3n) [52]: Orange yellow oil, 70%. H NMR (400 MHz, CDCl
3
) δ 7.34 - 7.25 (m, 5H), 3.55
(
s, 2H), 3.45 (s, 2H), 2.35 (s, 3H). 19F NMR (376 MHz, CDCl
3
) δ -44.0 (s, 3F). 13C NMR (101
3
MHz, CDCl ) δ 138.0 (s), 129.1 (s), 128.4 (s), 128.3 (q, J = 311.8 Hz), 127.4(s), 99.0 (s), 63.1 (q,
+
J = 4.1 Hz), 60.0 (s), 45.9 (s), 41.9 (s). GC-MS (EI): Calculated for C12
H
12
F
3
NS [M] : 259.1;
Found: 259.1.
1
(
3o) [49]: Yellow oil, 59%. H NMR (400 MHz, CDCl
3
) δ 7.35 - 7.29 (m, 2H), 7.26 - 7.20 (m,
) δ -44.1 (s, 3F).
) δ 139.9 (s), 128.52 (s), 128.48 (q, J = 311.5 Hz), 128.45 (s), 126.6
s), 103.0 (s), 58.0 (q, J = 4.3 Hz), 34.4 (s), 22.4 (s). GC-MS (EI): Calculated for C11
S [M]+:
30.0; [M-CF
]+: 161.0; Found [M-CF ]+: 161.1.
19
3
H), 2.88 (t, J = 7.4 Hz, 2H), 2.68 (t, J = 7.4 Hz, 2H). F NMR (376 MHz, CDCl
3
13C NMR (101 MHz, CDCl
3
(
H
F
9 3
2
3
3
Declaration of interests
☒
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐
The authors declare the following financial interests/personal relationships which may be
considered as potential competing interests
Acknowledgements
The authors thank the National Natural Science Foundation (21421002, 21672242,
2
1971252), Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS)
QYZDJSSW-SLH049), Youth Innovation Promotion Association CAS (2019256), the Fujian
Institute of Innovation, CAS (FJCXY18040102), Shanghai Research Institute of Chemical
(

Industry Co., LTD. (SKL-LCTP-201802), the Key Project of Hunan Provincial Education
Department (No. 17A190), the Zhengxiang Scholar Program of the University of South China,
Hunan Provincial Hengyang City Joint Fund (2017JJ4050), Hunan graduate science and
technology innovation projects (2018-400), Program for Innovative talent team of Hengyang
(
2017-1), the Key Project of Hengyang Science and Technology Department(2017KJ166), Hunan
Provincial Key Lab of Dark Tea and Jin-Hua (2016TP1022), and the Natural Science Foundation
of Hunan Province (No.2017JJ2018) for financial support.
Appendix A. Supplementary data
Supplementary data associated with this article can be found in the online version.
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