Radical coupling of arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents to access arylthiodifluoromethylated alkynes

Article abstract of DOI:10.1016/j.jfluchem.2020.109715

A practical and efficient radical coupling of easily available arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents has been reported. Under transition metal-free conditions, aryl-substituted EBXs were converted to the corresponding ArSCF₂-substituted alkynes in moderate to good yields, whereas TIPS-EBX underwent silver-catalyzed decarboxylative conditions to deliver the desired coupling products. The synthetic utility of this protocol was demonstrated through the transformation of resulting product to other ArSCF₂-substituted alkynes and alkenes.

Full text of DOI:10.1016/j.jfluchem.2020.109715

Journal Pre-proof
Radical coupling of arylthiodifluoroacetic acids and
ethynylbenziodoxolone (EBX) reagents to access
arylthiodifluoromethylated alkynes
Ya-Ling Liu, Xiao-Lei Zhu, Yangen Huang, Feng-Ling Qing, Xiu-Hua
Xu
PII:
S0022-1139(20)30413-9
DOI:
https://doi.org/10.1016/j.jfluchem.2020.109715
FLUOR 109715
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
6 November 2020
14 December 2020
14 December 2020
Please cite this article as: Liu Y-Ling, Zhu X-Lei, Huang Y, Qing F-Ling, Xu X-Hua, Radical
coupling of arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents to access
arylthiodifluoromethylated alkynes, Journal of Fluorine Chemistry (2020),
doi: https://doi.org/10.1016/j.jfluchem.2020.109715
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Radical coupling of arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX)
reagents to access arylthiodifluoromethylated alkynes
a
a
a,*
a,b
b*
Ya-Ling Liu , Xiao-Lei Zhu , Yangen Huang , Feng-Ling Qing , Xiu-Hua Xu
aCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North
Renmin Lu, Shanghai 201620, China
bKey Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, University of Chinese Academy of Science, Chinese Academy of
Science, 345 Lingling Lu, Shanghai 200032, China
Tel.: 86-21-54925191; Fax: 86-21-64166128; E-mail: hyg@dhu.edu.cn, xuxiuhua@sioc.ac.cn

Corresponding author. Tel.: +86 21 54925191; fax: +86 21 64166128.
E-mail address: hyg@dhu.edu.cn (Y. Huang), xuxiuhua@sioc.ac.cn (X.-H. Xu).
Graphical Abstract
Highlights




Oxidative decarboxylation of arylthiodifluoroacetic acids.
Alkynylation with ethynylbenziodoxolone (EBX) reagents.
Facile synthesis of arylthiodifluoromethylated alkynes.
Radical coupling reaction.
1

Abstract
A practical and efficient radical coupling of easily available arylthiodifluoroacetic acids and
ethynylbenziodoxolone (EBX) reagents has been reported. Under transition metal-free conditions, aryl-
substituted EBXs were converted to the corresponding ArSCF -substituted alkynes in moderate to good
2
yields, whereas TIPS-EBX underwent silver-catalyzed decarboxylative conditions to deliver the desired
coupling products. The synthetic utility of this protocol was demonstrated through the transformation of
resulting product to other ArSCF -substituted alkynes and arenes.
2
Keywords: Radical coupling; decarboxylation; arylthiodifluoroacetic acid; ethynylbenziodoxolone
EBX) reagent; transition-metal-free; alkyne.
(
1
. Introduction
Sulfur and fluorine are both leading constituents of the pharmaceuticals [1]. Recently, there has been
increasing interest in functional groups that contain fluorine and sulfur atoms [2]. To modify the
properties of organic molecules, new emerging fluorinated substituents are continuously being
developed. In this context, arylthiodifluoromethyl (ArSCF
of drug discovery and material sciences. For instance, ArSCF
exhibited potential activity against wild-type HIV-1 reverse transcriptase [3], and ArSCF
2
) group has found applications with the realm
-substituted benzo[d]oxazole (A)
-substituted
2
2
alkynes (B) demonstrated attractive liquid-crystalline properties [4] (Figure 1). Furthermore, ArSCF
group is a versatile precursor for the preparation other fluorine-containing moieties, such as
difluoromethyl, difluoromethylene, and difluoroalkyl [5].
2
2

Figure 1 Applications of ArSCF -containing compounds
2
From a retrosynthetic point of view, ArSCF -substituted compounds could be assembled through four
2
approaches, including fluorination of sulfur-containing compounds [6] (Figure 2a), difluoroalkylation of
thiophenol derivatives [7] (Figure 2b), difluoroalkylthiolation of aromatic compounds [8] (Figure 2c),
and direct arylthiodifluoromethylation reactions [9] (Figure 2d). However, most of the aforementioned
methods involved the preparation of ArSCF
2
-substituted alkanes and arenes. In comparison, the
synthesis of ArSCF -substituted alkenes [10] and alkynes [6d,11] remains largely unexplored, despite
2
alkenes and alkynes are common structural elements and serve as valuable building blocks in organic
synthesis.
Figure 2 Retrosynthetic analysis of ArSCF R
2
There are mainly two methods have been reported for the synthesis of ArSCF -substituted alkynes.
2
Fuchigami reported the electrochemical fluorination of propargyl aryl sulfides with HF salts as the
fluorinating reagent and supporting electrolyte [6d] (Scheme 1a). This reaction proceeds through the
anodic oxidation at the arylthio group, followed by deprotonation and subsequent fluorination. The
3

mono-fluorinated products and di-fluorinated products were obtained selectively depending on the
supporting HF salt used and electricity. Nenajdenko developed a three-step synthesis of ArSCF
substituted alkynes from aromatic aldehydes with ArSCF CF -substituted compounds as the key
intermediate [11] (Scheme 1b). However, the multistep preparation restricts the wide application of this
2
-
2
2
route. Hence, the development of new synthetic methods of ArSCF
2
-substituted alkynes is of high
demand.
Recently, we disclosed a silver-catalyzed radical arylthiodifluoromethylation of heteroaromatic
compounds with arylthiodifluoroacetic acids for the preparation of ArSCF -substituted heteroarenes
9g]. As part of our ongoing effort in the preparation of fluorine-containing alkynes [12], herein we
2
[
report a general and practical synthesis ArSCF -substituted alkynes from the radical coupling of
2
arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents that are known to serve as
facile radical acceptors [13,14] (Scheme 1c).
Scheme 1 Synthesis of ArSCF -substituted alkynes
2
4

2
. Results and Discussion
We began our study by investigating the coupling reaction between 1-(phenylethynyl)-1,2-
benziodoxol-3(1H)-one (Ph-EBX, 1a) and phenylthiodifluoroacetic acid (2a) to optimize the reaction
conditions (Table 1). To our delight, the desired coupling product 3a was formed in 42% yield with
o
K
2
S
2
O
8
as the oxidant and DCE/H
salts including Na and (NH
identified to be optimal (entry 3). In contrast, the reaction did not occur when PhI(OAc)
was employed as the oxidant (entries 4 and 5). Then, several solvents were tested, among which
toluene/H O provided the optimal yield (entries 6-9). Furthermore, changing the ratio of toluene to H
led to lower yields (entries 10 and 11). Raising or lowering the temperature was also detrimental to the
reaction (entries 12 and 13). Finally, catalytic amount of AgNO or stoichiometric amount of K CO
2
O as the solvent at 70 C for 12 h (entry 1). Other peroxydisulfate
2
S
2
O
8
4
)
2
S
2
O
8
could also promoted the reaction, and (NH
4
)
S
2 2
O
8
was
2
or t-BuOOH
2
2
O
3
2
3
5

was added to the reaction mixture, but no further increase in the yield was observed (entries 14 and 15).
Notably, 1a was totally consumed under the optimized conditions, probably due to its low thermal and
hydrolytic stability [15]. Furthermore, some arylthiodifluoromethylated arenes were formed as
byproducts, which were tentatively ascribed to the attack of ArSCF
2
radical onto the phenyl ring (see
the supporting information).
Table 1. Optimization of reaction conditions.a
o
Yield (%)b
Entry
Oxidant
Solvent
Temperature ( C)
1
2
3
4
5
6
7
8
9
K
2
S
2
O
8
DCE/H
DCE/H
DCE/H
DCE/H
DCE/H
2
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
70
70
70
70
70
70
70
70
70
70
70
60
80
70
70
42
11
51
0
Na
2
S
2
O
8
2
2
2
2
(NH
4
)
2
S
2
O
8
PhI(OAc)
t-BuOOH
2
0
(NH
(NH
(NH
(NH
(NH
(NH
(NH
4
4
4
4
4
4
4
)
)
)
)
)
)
)
2
2
2
2
2
2
2
S
S
S
S
S
S
S
2
2
2
2
2
2
2
O
8
O
8
O
8
O
8
O
8
O
8
O
8
DMSO/H
THF/H O (1:1)
acetone/H O (1:1)
2
O (1:1)
43
24
0
2
2
toluene/H
toluene/H
toluene/H
toluene/H
toluene/H
toluene/H
toluene/H
2
O (1:1)
O (2:1)
O (1:2)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
71
58
66
48
66
66
55
1
1
1
1
1
1
0
2
2
2
2
2
2
1
2
3
(NH
(NH
(NH
4
4
4
)
)
)
2
2
2
S
S
S
2
2
2
O
8
O
8
O
8
4d
5c
aReaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), oxidant (0.3 mmol), solvent (4.0 mL), temperature, under N
, 12 h
.
2
bYields were determined by 19F NMR spectroscopy using trifluoromethylbenzene as an internal standard.
cAgNO
dK
CO
(0.02 mmol) was added.
3
2
3
(0.4 mmol) was added.
Table 2. Scope of the coupling of arylthiodifluoroacetic acids and alkynylbenziodoxolones.a
6

aReaction conditions: 1 (0.6 mmol), 2 (1.2 mmol), (NH
yields.
)
S
2
O
8
(0.9 mmol), toluene/H
O (6.0/6.0 mL), 70 C, under N
o
, 12 h, isolated
4
2
2
2
bReaction conditions: 1 (0.6 mmol), 2 (0.6 mmol), AgNO
(0.15 mmol), K
S
2
O
8
(1.2 mmol), acetone/H
O (3.0/3.0 mL), 50 C, under
o
3
2
2
N
2
, 24 h, isolated yields.
With the optimized conditions established, the scope of arylthiodifluoroacetic acids and EBX
reagents was examined (Table 2). Various arylthiodifluoroacetic acids (2b-l) bearing either electron-
donating or electron-withdrawing groups at different positions of the aromatic ring reacted with 1a
7

smoothly to deliver the corresponding products (3b-l) in moderate to good yields. A series of aryl-
substituted EBXs also worked well, affording products 3m-p in moderate yields. The mild reaction
conditions allow the tolerance of a series of functional groups, such as alkyl, alkoxy, cyano, and halides.
When alkyl-substituted EBXs were subjected to the standard reaction conditions, the desired products
were not detected. TIPS-EBX was also investigated, but low yield was observed. Fortunately, under
silver-catalyzed decarboxylative alkynylation conditions [14a,f], TIPS-EBX was converted to the
coupling products 3q-s in good yields.
The ArSCF
valuable compounds. To showcase such possibilities, the transformation of product 3r has been
performed (Scheme 2). Treatment of 3r with TBAF afforded ArSCF -substituted terminal alkyne 3t in
8% yield. In the presence of NBS and catalytic amount of AgNO , 3t was readily converted to the
corresponding alkynyl bromide 3u. Furthermore, hydrogenation of 3t with Pd/CaCO under H
atmosphere delivered ArSCF -substituted alkene 4 in 85% yield.
2
-substituted alkynes present versatile building blocks for the synthesis of other
2
5
3
3
2
2
Scheme 2 Transformation of 3r
In order to gain mechanistic insight, a radical scavenger TEMPO (2,2,6,6-tetramethylpiperidine-1-
oxyl) was added to the standard conditions. The target reaction was completely quenched (see the
supporting information), which indicated that a radical process was probably involved in this reaction.
On the basis of this result and previous reports [14,16], a plausible reaction mechanism was proposed in
8

Scheme 3. Initially, peroxydisulfate anion decomposes into sulfate radical anion under thermal
conditions. Then, the oxidative decarboxylation of arylthiodifluoroacetic acids 2 with sulfate radical
anion generates ArSCF
2
radical. Subsequently, the addition of ArSCF radical to EBX reagents 1 in the
2
α position next to the iodine affords radical intermediate A, although addition onto the β position
followed by a 1,2-shift or a concerted mechanism cannot be excluded at this stage [17]. Finally,
intermediate A undergoes radical elimination reaction to yield the coupling product 3 along with
benziodoxolonyl radical. Benziodoxolonyl radical might be converted to 2-iodobenzoic acid through a
reduction/protonation or H-abstraction process [14a,e,16].
Scheme 3 Proposed reaction mechanism
3
. Conclusion
In conclusion, we have developed a convenient and efficient synthesis of ArSCF -substituted
2
alkynes from the radical coupling of easily available arylthiodifluoroacetic acids and
ethynylbenziodoxolone (EBX) reagents. The resulting ArSCF -substituted alkynes constitute useful
building blocks for the preparation of ArSCF -substituted compounds. Further exploration of the
2
2
applications of other easily available fluorine-containing carboxylic acids in the synthesis of valuable
fluorine-containing compounds are currently in progress.
9

4
. Experimental Section
4
.1. General information
1
13
19
H NMR (TMS as the internal standard), C NMR, and F NMR spectra (CFCl as the outside
3
standard and low field is positive) were recorded on a 400 MHz spectrometer. 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. HRMS data
were obtained on a GC/MS TOF high resolution mass spectrometer equipped with a liquid
chromatography system. All reagents were used as received from commercial sources without further
purification. EBX reagents were prepared following the reported procedures [14].
4
.2. Typical procedure for the preparation of arylthiodifluoroacetic acids [18]
To a 50 mL oven-dried Schlenk tube equipped with a stir bar was added thiophenol (3.0 mmol, 1.0
equiv) under N atmosphere. 1,4-Dioxane (10.0 mL) was added to dissolve the thiophenol. Then, NaH
60% purity) (132.0 mg, 3.3 mmol, 1.1 equiv) and 1,4-dioxane (2.0 mL) were added under N
2
(
2
atmosphere. The solution was stirred at room temperature for 30 min. Then BrCF
2
COONa (647.1 mg,
o
3
.3 mmol, 1.1 equiv) and 1,4-dioxane (3.0 mL) were added. After the mixture was heated at 60 C for
hours (monitor by TLC), then the mixture was cooled down to room temperature and acidified with 3M
HCl (aq) to pH = 1. The mixture was extracted with ethyl acetate for three times. The combined organic
phase was washed by saturated brines and dried over MgSO . After the solution was filtered and the
4
solvent was evaporated under vacuum, the crude product was purified by flash column chromatography
using petroleum ether and ethyl acetate as eluent to give the product 2.
4
.2.1. 2,2-Difluoro-2-(o-tolylthio)acetic acid (2b). After purification by silica gel column
1
chromatography (EtOAc), compound 2b was obtained as a yellow oil (263.1 mg, 40%). H NMR (400
MHz, DMSO-d
6
) δ ppm 14.50 (s, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.37-7.32 (m, 2H), 7.23 (t, J = 7.3 Hz,
1
9
13
1
H), 2.45 (s, 3H); F NMR (376 MHz, DMSO-d
6
) δ ppm -80.68 (s); C NMR (101 MHz, DMSO-d ) δ
6
1
0

ppm 163.1 (t, J = 30.8 Hz), 144.1, 138.6, 131.4, 131.2, 127.1, 124.4, 121.1 (t, J = 287.7 Hz), 21.2; IR
-1
-
(
thin film) ν 3394, 1658, 1119, 1048, 1023, 994, 824, 761 cm ; MS (ESI): m/z 217 [M-H] ; HRMS
-
(
ESI) m/z: [M-H] Calcd. for C
9
H
7
F
2
2
O S 217.0140; Found 217.0140.
4
.2.2. 2,2-Difluoro-2-(3-fluorophenylthio)acetic acid (2f). After purification by silica gel column
1
chromatography (EtOAc), compound 2f was obtained as a brown oil (298.6 mg, 45%). H NMR (400
1
9
MHz, DMSO-d ) δ ppm 7.51-7.45 (m, 1H), 7.41 (d, J = 7.4 Hz, 2H), 7.35 (t, J = 9.0 Hz, 1H); F NMR
6
1
3
(376 MHz, DMSO-d
6
) δ ppm -80.21 (s, 2F), -111.52 – -111.59 (m, 1F); C NMR (101 MHz, DMSO-
d
6
) δ ppm 162.7 (t, J = 30.3 Hz), 161.0 (d, J = 248.8 Hz), 132.7 (d, J = 8.5 Hz), 131.7, 127.0 (t, J = 3.3
Hz), 122.9 (d, J = 22.4 Hz), 120.9 (t, J = 287.9 Hz), 118.2 (d, J = 21.1 Hz); IR (thin film) ν 3402, 1660,
-1
-
-
1
023, 994, 824, 762, 519 cm ; MS (ESI): m/z 221 [M-H] ; HRMS (ESI) m/z: [M-H] Calcd. for
C
8
H
4
F
3
O
2
S 220.9890; Found 220.9890.
4
.2.3. 2-(2,5-Dimethylphenylthio)-2,2-difluoroacetic acid (2l). After purification by silica gel column
o
chromatography (EtOAc), compound 2l was obtained as a brown solid (266.8 mg, 38%). m.p. 58-60 C;
1H NMR (400 MHz, DMSO-d ) δ ppm 7.40 (s, 1H), 7.28-7.22 (m, 2H), 2.40 (s, 3H), 2.28 (s, 3H); 19F
6
13
NMR (376 MHz, DMSO-d
6
) δ ppm -80.59 (s); C NMR (101 MHz, DMSO-d
6
) δ ppm 163.0 (t, J =
3
0.6 Hz), 140.8, 138.8, 136.6, 132.3, 131.2, 123.9 (t, J = 1.8 Hz), 121.0 (t, J = 288.4 Hz), 20.8, 20.6; IR
-1
(
thin film) ν 2861, 2692, 1743, 1489, 1433, 1281, 1089, 970, 815, 710, 691 cm ; MS (ESI): m/z 231
-
-
[
M-H] ; HRMS (ESI) m/z: [M-H] Calcd. for C10
H
9
F
2
2
O S 231.0297; Found 231.0298.
4
.3. General procedures for the transition-metal-free coupling of arylthiodifluoroacetic acids and aryl-
substituted EBXs
To a sealed tube equipped with a stir bar were added aryl-substituted EBX 1 (0.6 mmol, 1.0 equiv) and
NH (205.4 mg, 0.9 mmol, 1.5 equiv). The tube was evacuated and backfilled with pure N for
O (6.0/6.0 mL) were
(
4
)
2
S
2
O
8
2
three times. Then arylthiodifluoroacetic acid 2 (1.2 mmol, 2.0 equiv) in toluene/H
2
o
added. The tube was sealed and the mixture was heated at 70 C in an oil bath for 12 h. After the
1
1

reaction was complete, saturated NaHCO
ethyl acetate for three times. The combined organic layer was washed with brine, dried over anhydrous
Na SO , and concentrated under reduced pressure. The resulting residue was purified by silica gel flash
column chromatography to give the desired product 3a-p.
3
solution was added. The resulting mixture was extracted with
2
4
4
.3.1. (1,1-Difluoro-3-phenylprop-2-ynyl)(phenyl)sulfane (3a). After purification by silica gel column
1
chromatography (n-hexane), compound 3a was obtained as a yellowish oil (93.7 mg, 60%). H NMR
(400 MHz, CDCl
3
) δ ppm 7.67-7.58 (m, 2H), 7.42-7.36 (m, 1H), 7.36-7.29 (m, 5H), 7.29-7.21 (m, 2H);
19F NMR (376 MHz, CDCl
) δ ppm -58.45 (s); C NMR (101 MHz, CDCl
13
) δ ppm 135.6, 131.1 (t, J
3
3
=
=
1.9 Hz), 129.4, 129.2, 128.1, 127.4, 126.0, 118.6, 116.9 (t, J = 266.6 Hz), 89.4 (t, J = 6.2 Hz), 79.2 (t, J
-1
40.2 Hz); IR (thin film) ν 2925, 2232, 1474, 1278, 1107, 1023, 1001, 970, 747, 686 cm ; MS (EI):
+
+
m/z 260 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C15
H
10
2
F S: 260.0466; Found: 260.0468.
4
.3.2. (1,1-Difluoro-3-phenylprop-2-ynyl)(o-tolyl)sulfane (3b). After purification by silica gel column
1
chromatography (n-hexane), compound 3b was obtained as a yellowish oil (70.7 mg, 43%). H NMR
400 MHz, CDCl ) δ ppm 7.63 (d, J = 7.7 Hz, 1H), 7.37-7.30 (m, 3H), 7.29-7.24 (m, 4H), 7.19-7.11 (m,
(
3
1
9
13
1
1
H), 2.50 (s, 3H); F NMR (376 MHz, CDCl
3
) δ ppm -57.74 (s); C NMR (101 MHz, CDCl
3
) δ ppm
43.1, 137.6, 131.1 (t, J = 2.1 Hz), 129.9, 129.8, 129.2, 127.4, 125.5, 125.3, 118.6 (t, J = 2.4 Hz), 117.3
(t, J = 266.8 Hz), 89.1 (t, J = 6.0 Hz), 79.2 (t, J = 40.3 Hz), 20.4; IR (thin film) ν 2925, 2232, 1489,
-1
+
+
1
278, 1106, 1022, 969, 752, 687 cm ; MS (EI): m/z 274 [M] ; HRMS (EI-TOF): m/z [M] Calculated
for C16
12 2
H F S: 274.0622; Found: 274.0626.
4
.3.3. (2-Chlorophenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3c). After purification by silica
gel column chromatography (n-hexane), compound 3c was obtained as a yellowish oil (84.8 mg, 48%).
1H NMR (400 MHz, CDCl
3
) δ ppm 7.70 (dd, J = 7.6, 1.6 Hz, 1H), 7.41 (dd, J = 8.0, 1.4 Hz, 1H), 7.33-
1
9
13
7
.26 (m, 4H), 7.26-7.16 (m, 3H); F NMR (376 MHz, CDCl
3
) δ ppm -57.47 (s); C NMR (101 MHz,
CDCl
3
) δ ppm 138.9, 137.7, 131.1 (t, J = 1.9 Hz), 130.7, 129.33, 129.29, 127.4, 126.2, 125.4, 118.3 (t, J
=
2.4 Hz), 116.7 (t, J = 268.0 Hz), 89.5 (t, J = 6.2 Hz), 78.8 (t, J = 39.7 Hz); IR (thin film) ν 2924, 2230,
1
2

-1
+
+
1
489, 1430, 1280, 1107, 966, 751, 687, 658 cm ; MS (EI): m/z 294 [M] ; HRMS (EI-TOF): m/z [M]
Calculated for C15 ClF S: 294.0076; Found: 294.0078.
H
9
2
4
.3.4. (2-Bromophenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3d). After purification by silica
gel column chromatography (n-hexane), compound 3d was obtained as a yellowish oil (71.2 mg, 35%).
1H NMR (400 MHz, CDCl
3
) δ ppm 7.74 (dd, J = 7.7, 1.7 Hz, 1H), 7.62 (dd, J = 7.9, 1.5 Hz, 1H), 7.37-
1
9
13
7
.28 (m, 3H), 7.30-7.23 (m, 3H), 7.22-7.17 (m, 1H); F NMR (376 MHz, CDCl
3
) δ ppm -57.55 (s); C
NMR (101 MHz, CDCl
3
) δ ppm 137.3, 132.7, 131.1 (t, J = 1.8 Hz), 130.6, 129.7, 129.3, 127.8, 127.4,
1
26.9, 118.4 (t, J = 2.4 Hz), 116.8 (t, J = 268.1 Hz), 89.6 (t, J = 6.2 Hz), 78.8 (t, J = 39.7 Hz); IR (thin
-1
+
film) ν 2924, 2230, 1489, 1445, 1279, 1106, 965, 801, 751, 687 cm ; MS (EI): m/z 338 [M] ; HRMS
+
(
EI-TOF): m/z [M] Calculated for C15
H
9
BrF S: 337.9571; Found: 337.9570.
2
4
.3.5. (1,1-Difluoro-3-phenylprop-2-yn-1-yl)(m-tolyl)sulfane (3e). After purification by silica gel
1
column chromatography (n-hexane), compound 3e was obtained as a yellowish oil (83.9 mg, 50%). H
NMR (400 MHz, CDCl
3
) δ ppm 7.42-7.40 (m, 2H), 7.36-7.28 (m, 3H), 7.28-7.16 (m, 4H), 2.27 (s, 3H);
19F NMR (376 MHz, CDCl
) δ ppm -58.54 (s); C NMR (101 MHz, CDCl
13
) δ ppm 138.0, 136.2, 132.6,
3
3
1
8
1
31.0 (t, J = 2.1 Hz), 130.1, 129.1, 127.9, 127.4, 125.6, 118.6 (t, J = 2.4 Hz), 117.0 (t, J = 266.6 Hz),
9.3 (t, J = 6.2 Hz), 79.2 (t, J = 40.3 Hz), 20.2; IR (thin film) ν 2919, 2231, 1600, 1504, 1467, 1387,
-1
+
+
218, 1103, 1022, 971, 817, 637 cm ; MS (EI): m/z 274 [M] ; HRMS (EI-TOF): m/z [M] Calculated
for C16
12 2
H F S: 274.0622; Found: 274.0624.
4
.3.6. (1,1-Difluoro-3-phenylprop-2-yn-1-yl)(3-fluorophenyl)sulfane (3f). After purification by silica
gel column chromatography (n-hexane), compound 3f was obtained as a yellowish oil (80.1 mg, 48%).
1H NMR (400 MHz, CDCl
) δ ppm 7.40 (dt, J = 7.7, 1.3 Hz, 1H), 7.38-7.24 (m, 7H), 7.09 (tdd, J = 8.4,
3
1
9
13
2
.6, 1.0 Hz, 1H); F NMR (376 MHz, CDCl
NMR (101 MHz, CDCl
Hz), 118.4 (t, J = 2.4 Hz), 116.6 (t, J = 267.7 Hz), 116.4 (d, J = 21.1 Hz), 89.7 (t, J = 6.1 Hz), 78.9 (t, J =
3
) δ ppm -58.18 (s, 2F), -111.41 – -111.52 (m, 1F); C
3
) δ ppm 160.1 (d, J = 250.8 Hz), 131.1, 129.4, 129.3, 127.5, 122.1 (d, J = 22.1
1
3

-
1
3
2
9.9 Hz); IR (thin film) ν 2926, 2231, 1580, 1489, 1280, 1220, 970, 878, 686, 679 cm ; MS (EI): m/z
+
+
78 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C15
H
9
F S: 278.0372; Found: 278.0375.
3
4
.3.7. (3-Bromophenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3g). After purification by silica
gel column chromatography (n-hexane), compound 3g was obtained as a yellowish oil (97.6 mg, 48%).
1H NMR (400 MHz, CDCl
) δ ppm 7.77 (s, 1H), 7.58-7.46 (m, 2H), 7.38-7.29 (m, 3H), 7.27-7.24 (m,
3
1
9
13
2
H), 7.22-7.14 (m, 1H); F NMR (376 MHz, CDCl
3
) δ ppm -58.16 (s); C NMR (101 MHz, CDCl
3
) δ
ppm 137.9, 134.0, 132.5, 131.1 (t, J = 2.1 Hz), 129.4, 129.3, 127.9, 127.5, 121.6, 118.3 (t, J = 2.5 Hz),
1
1
16.6 (t, J = 267.5 Hz), 89.9 (t, J = 6.1 Hz), 78.9 (t, J = 40.0 Hz); IR (thin film) ν 2925, 2231, 1562,
-1
+
+
444, 1401, 1280, 1109, 968, 753, 680 cm ; MS (EI): m/z 338 [M] ; HRMS (EI-TOF): m/z [M]
Calculated for C15
H
9
BrF S: 337.9571; Found: 337.9565.
2
4
.3.8. (4-(Tert-butyl)phenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3h). After purification by
silica gel column chromatography (n-hexane), compound 3h was obtained as a yellow solid (85.4 mg,
o
1
4
7
5%). m.p. 66-68 C. H NMR (400 MHz, CDCl
3
) δ ppm 7.53 (d, J = 8.3 Hz, 2H), 7.41-7.33 (m, 3H),
19
13
.31-7.21 (m, 4H), 1.24 (s, 9H); F NMR (376 MHz, CDCl
3
) δ ppm -58.49 (s); C NMR (101 MHz,
CDCl
3
) δ ppm 152.8, 135.4, 131.0 (t, J = 2.1 Hz), 129.1, 127.4, 125.2, 122.6, 118.6 (t, J = 2.2 Hz), 117.2
(
t, J = 266.0 Hz), 89.5 (t, J = 6.2 Hz), 79.2 (t, J = 40.3 Hz), 33.8, 30.1; IR (thin film) ν 2923, 2233, 1489,
-1
+
+
1
279, 1108, 1026, 970, 780, 687 cm ; MS (EI): m/z 316 [M] ; HRMS (EI-TOF): m/z [M] Calculated
for C19
18 2
H F S: 316.1092; Found: 316.1085.
4
.3.9. (1,1-Difluoro-3-phenylprop-2-yn-1-yl)(4-fluorophenyl)sulfane (3i). After purification by silica gel
1
column chromatography (n-hexane), compound 3i was obtained as a yellowish oil (83.4 mg, 50%). H
NMR (400 MHz, CDCl
3
) δ ppm 7.64-7.54 (m, 2H), 7.34-7.30 (m, 3H), 7.29-7.23 (m, 2H), 7.06-6.98 (m,
1
9
13
2
H); F NMR (376 MHz, CDCl
3
) δ ppm -58.98 (s, 2F), -105.09 – -111.47 (m, 1F); C NMR (101
MHz, CDCl
3
) δ ppm 162.1 (d, J = 252.6 Hz), 137.9 (d, J = 8.8 Hz), 131.0 (t, J = 2.0 Hz), 129.3, 127.5,
1
21.2 (t, J = 1.8 Hz), 118.4 (t, J = 2.4 Hz), 116.7 (td, J = 266.9, 2.0 Hz), 115.3 (d, J = 22.2 Hz), 89.6 (t, J
=
6.2 Hz), 79.0 (t, J = 40 Hz); IR (thin film) ν 2233, 1583, 1487, 1277, 1214, 1104, 997, 965, 662, 687,
1
4

-1
+
+
6
36 cm ; MS (FI): m/z 278 [M] ; HRMS (FI-TOF): m/z [M] Calculated for C15
H
9
3
F S: 278.0372;
Found: 278.0376.
4
.3.10. (4-Chlorophenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3j). After purification by silica
gel column chromatography (n-hexane), compound 3j was obtained as a yellow solid (85.0 mg, 48%).
o
1
m.p. 71-73 C; H NMR (400 MHz, CDCl
3
) δ ppm 7.53 (d, J = 8.5 Hz, 2H), 7.37-7.30 (m, 4H), 7.30-
1
9
13
7
1
.24 (m, 3H); F NMR (376 MHz, CDCl
3
) δ ppm -58.44 (s); C NMR (101 MHz, CDCl
3
) δ ppm
36.8, 136.1, 131.1 (t, J = 2.0 Hz), 129.3, 128.4, 127.5, 124.3, 118.4 (t, J = 2.5 Hz), 116.5 (t, J = 267.3
Hz), 89.7 (t, J = 6.1 Hz), 78.9 (t, J = 40.0 Hz); IR (thin film) ν 2924, 2231, 1598, 1474, 1387, 1277,
-1
+
+
1
079, 946, 825, 687 cm ; MS (EI): m/z 294 [M] ; HRMS (EI-TOF): m/z [M] Calculated for
C
15
H
9
ClF S: 294.0076; Found: 294.0080.
2
4
.3.11. (4-Bromophenyl)(1,1-difluoro-3-phenylprop-2-yn-1-yl)sulfane (3k). After purification by silica
gel column chromatography (n-hexane), compound 3k was obtained as a white solid (126.2 mg, 62%).
o
1
m.p. 70-72 C. H NMR (400 MHz, CDCl
3
) δ ppm 7.47-7.46 (m, 4H), 7.34-7.33 (m, 3H), 7.29-7.25 (m,
1
9
13
2
1
H); F NMR (376 MHz, CDCl
3
) δ ppm -58.35 (s); C NMR (101 MHz, CDCl
3
) δ ppm 137.0, 131.4,
31.1 (t, J = 1.9 Hz), 129.3, 127.5, 124.9 (t, J = 1.5 Hz), 124.4, 118.3 (t, J = 2.4 Hz), 116.4 (t, J = 267.4
Hz), 89.7 (t, J = 6.2 Hz), 78.9 (t, J = 40.0 Hz); IR (thin film) ν 2233, 1488, 1471, 1279, 1105, 1019, 821,
-
1
+
+
7
3
01, 686 cm ; MS (FI): m/z 338 [M] ; HRMS (FI-TOF): m/z [M] Calculated for C15
H
9
BrF S:
2
37.9571; Found: 337.9575.
4
.3.12. (1,1-Difluoro-3-phenylprop-2-yn-1-yl)(2,5-dimethylphenyl)sulfane (3l). After purification by
silica gel column chromatography (n-hexane), compound 3l was obtained as a yellowish oil (77.8 mg,
1
4
5%). H NMR (400 MHz, CDCl
3
) δ ppm 7.43 (s, 1H), 7.32-7.29 (m, 3H), 7.25-7.21 (m, 2H), 7.12-7.05
19
13
(
m, 2H), 2.43 (s, 3H), 2.21 (s, 3H); F NMR (376 MHz, CDCl
3
) δ ppm -57.81 (s); C NMR (101 MHz,
CDCl
3
) δ ppm 139.9, 138.0, 135.1, 131.0 (t, J = 2.1 Hz), 130.7, 129.6, 129.1, 127.4, 124.8, 118.6 (t, J =
1
.8 Hz), 117.4 (t, J = 266.6 Hz), 89.1 (t, J = 6.1 Hz), 79.3 (t, J = 40.1 Hz), 19.8, 19.6; IR (thin film) ν
1
5

-1
+
2
923, 2233, 1489, 1444, 1279, 1106, 969, 754, 687 cm ; MS (EI): m/z 288 [M] ; HRMS (EI-TOF): m/z
+
[
M] Calculated for C17
H
14
2
F S: 288.0779; Found: 288.0781.
4
.3.13. 2-(3-((4-Bromophenyl)thio)-3,3-difluoroprop-1-yn-1-yl)benzonitrile (3m). After purification by
silica gel column chromatography (n-hexane/EtOAc = 20:1), compound 3m was obtained as a yellow
o
1
solid (124.6 mg, 57%). m.p. 90-93 C; H NMR (400 MHz, CDCl
3
) δ ppm 7.68-7.62 (m, 1H), 7.58-7.44
) δ ppm -59.97 (s); C NMR (101 MHz, CDCl ) δ ppm 137.2,
32.3 (t, J = 2.0 Hz), 132.0, 131.5, 129.5, 124.7, 124.3, 122.1 (t, J = 2.3 Hz), 116.0 (t, J = 268.8 Hz),
15.4, 114.8 (t, J = 2.1 Hz), 84.6 (t, J = 6.1 Hz), 84.2 (t, J = 41.2 Hz); IR (thin film) ν 2961, 2232, 1564,
1
9
13
(
m, 7H); F NMR (376 MHz, CDCl
3
3
1
1
1
-1
+
+
484, 1388, 1263, 1010, 973, 814, 688 cm ; MS (EI): m/z 363 [M] ; HRMS (EI-TOF): m/z [M]
Calculated for C16
H
8
BrF NS: 362.9523; Found: 362.9525.
2
4
.3.14. (4-Bromophenyl)(1,1-difluoro-3-(4-methoxyphenyl)prop-2-yn-1-yl)sulfane (3n). After
purification by silica gel column chromatography (n-hexane), compound 3n was obtained as a yellow
o
1
solid (113.0 mg, 51%). m.p. 48-50 C; H NMR (400 MHz, CDCl
3
) δ ppm 7.47-7.45 (m, 4H), 7.19-7.17
m, 1H), 6.94-6.87 (m, 2H), 6.83-6.82 (m, 1H), 3.72 (s, 3H); F NMR (376 MHz, CDCl ) δ ppm -58.39
) δ ppm 158.3, 137.0, 131.4, 128.6, 126.7, 125.0, 124.4, 123.5 (t, J =
.0 Hz), 119.3 (t, J = 2.5 Hz), 116.5 (t, J = 267.4 Hz), 116.1, 115.6 (t, J = 2.1 Hz), 89.7 (t, J = 6.1 Hz),
1
9
(
(
3
1
3
s); C NMR (101 MHz, CDCl
3
2
7
1;
8.6 (t, J = 40.1 Hz), 54.3; IR (thin film) ν 3066, 2970, 2240, 1607, 1581, 1301, 1010, 973, 778, 684 cm-
+
+
MS (EI): m/z 368 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C16
H
11BrF OS: 367.9690; Found:
2
3
67.9684.
4
.3.15. (4-Bromophenyl)(1,1-difluoro-3-(4-fluorophenyl)prop-2-yn-1-yl)sulfane (3o). After purification
by silica gel column chromatography (n-hexane), compound 3o was obtained as a yellow solid (117.9
o
1
mg, 55%). m.p. 84-86 C; H NMR (400 MHz, CDCl
3
) δ ppm 7.44 (s, 4H), 7.36-7.26 (m, 2H), 6.95 (t, J
1
9
13
=
8.6 Hz, 2H); F NMR (376 MHz, CDCl
3
) δ ppm -58.41 (s, 2F), -106.78 – -106.85 (m, 1F); C NMR
(101 MHz, CDCl
3
) δ ppm 161.4 (d, J = 253.5 Hz), 137.0, 133.2 (dt, J = 8.8, 2.1 Hz), 131.4, 124.9,
1
24.5, 116.4 (t, J = 267.6 Hz), 115.1, 114.5 (q, J = 2.5 Hz), 88.6 (t, J = 6.3 Hz), 78.8 (t, J = 40.3 Hz); IR
1
6

-1
(
thin film) ν 2919, 2231, 1600, 1504, 1467, 1387, 1218, 1103, 1022, 971, 817, 637 cm ; MS (EI): m/z
+
+
3
56 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C15
H
8
BrF S: 355.9477; Found: 355.9481.
3
4
.3.16. 4-(3-((4-Bromophenyl)thio)-3,3-difluoroprop-1-yn-1-yl)benzonitrile (3p). After purification by
silica gel column chromatography (n-hexane/EtOAc = 20:1), compound 3p was obtained as a yellow
o
1
solid (98.3 mg, 45%). m.p. 120-122 C; H NMR (400 MHz, CDCl
3
) δ 7.68-7.56 (m, 2H), 7.50-7.42 (m,
) δ -59.65 (s); C NMR (101 MHz, CDCl ) δ 137.0, 131.6 (t, J = 1.9
Hz), 131.5, 131.2, 124.7, 124.4, 123.1 (t, J = 2.4 Hz), 116.8, 116.2 (t, J = 268.3 Hz), 112.9, 87.1 (t, J =
1
9
13
6
H); F NMR (376 MHz, CDCl
3
3
6
8
3
.0 Hz), 82.3 (t, J = 40.5 Hz); IR (thin film) ν 2919, 2232, 1600, 1501, 1468, 1387, 1102, 1010, 972,
-1
+
+
36, 817 cm ; MS (EI): m/z 363 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C16
H
8
BrF NS:
2
62.9523; Found: 362.9518.
4
.4. General procedures for the silver-catalyzed coupling of arylthiodifluoroacetic acids and TIPS-EBX
In a sealed tube, TIPS-EBX (257.0 mg, 0.6 mmol, 1 equiv.), arylthiodifluoroacetic acid 2 (0.6 mmol, 1
equiv.), AgNO (25.5 mg, 0.15 mmol, 25 mol %), K (324.4 mg, 1.2 mmol, 2 equiv.), H O (3.0
3
2
S
2
O
8
2
mL) and acetone (3 mL) were added. The reaction mixture was stirred at 50 °C for 24 h. Water and
ethyl acetate were added to the reaction vessel and the aqueous layer was extracted with ethyl acetate.
The combined organic layer was washed with brine, dried over anhydrous Na
2
SO , and concentrated
4
under reduced pressure. The resulting residue was purified by silica gel flash column chromatography to
give the product 3q-s.
4
.4.1. (3-(4-Tert-butylphenylthio)-3,3-difluoroprop-1-ynyl)triisopropylsilane (3q). After purification by
silica gel column chromatography (n-hexane), compound 3q was obtained as a colorless oil (156.0 mg,
1
7
9
1
9%). H NMR (400 MHz, CDCl
3
) δ ppm 7.48 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 1.24 (s,
1
9
13
H), 0.95 (s, 21H); F NMR (376 MHz, CDCl
3
) δ ppm -58.64 (s); C NMR (101 MHz, CDCl
3
) δ ppm
52.5, 135.0, 125.2, 122.8, 115.8 (t, J = 266.0 Hz), 95.9 (t, J = 38.7 Hz), 92.9 (t, J = 5.0 Hz), 33.8, 30.2,
1
7

-
1
1
3
7.4, 9.9; IR (thin film) ν 2945, 2867, 1463, 1156, 1036, 982, 882, 830, 679, 661 cm ; MS (EI): m/z
+
+
96 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C22
H
34
F SSi: 396.2113; Found: 396.2110.
2
4
.4.2. (3-(4-Bromophenylthio)-3,3-difluoroprop-1-ynyl)triisopropylsilane (3r). After purification by
silica gel column chromatography (n-hexane), compound 3r was obtained as a colorless oil (156.0 mg,
1
19
6
2%). H NMR (400 MHz, CDCl
3
) δ ppm 7.45-7.40 (m, 4H), 0.96 (s, 21H); F NMR (376 MHz,
1
3
CDCl
3
) δ ppm -58.36 (s); C NMR (101 MHz, CDCl ) δ 136.6, 131.4, 125.2 (t, J = 1.6 Hz), 124.2,
3
1
1
15.3 (t, J = 267.3 Hz), 95.4 (t, J = 38.3 Hz), 93.7 (t, J = 5.0 Hz), 17.3, 9.8; IR (thin film) ν 2944, 2867,
-1
+
+
474, 1387, 1158, 978, 881, 818, 693 cm ; MS (EI): m/z 418 [M] ; HRMS (EI-TOF): m/z [M]
Calculated for C18
H25BrF
2
SSi: 418.0592; Found: 418.0589.
4
.4.3. (3,3-Difluoro-3-(3-fluorophenylthio)prop-1-ynyl)triisopropylsilane (3s). After purification by
silica gel column chromatography (n-hexane), compound 3s was obtained as a colorless oil (135.5 mg,
1
6
8
1
1
2
1
3%). H NMR (400 MHz, CDCl
3
) δ ppm 7.35 (d, J = 7.8 Hz, 1H), 7.34-7.23 (m, 2H), 7.06 (tdd, J =
19
.4, 2.6, 1.2 Hz, 1H), 0.96 (s, 21H); F NMR (376 MHz, CDCl
3
) δ ppm -58.31 (s, 2F), -111.59 – -
1
3
11.65 (m, 1F); C NMR (101 MHz, CDCl
3
) δ ppm 160.1 (d, J = 250.7 Hz), 130.7 (d, J = 3.2 Hz),
29.3 (d, J = 8.2 Hz), 128.0 (d, J = 8.0 Hz), 121.7 (d, J = 22.3 Hz), 116.2 (d, J = 21.2 Hz), 115.3 (t, J =
67.4 Hz), 95.4 (t, J = 38.2 Hz), 93.7 (t, J = 5.1 Hz), 17.3, 9.8; IR (thin film) ν 2946, 2868, 1588, 1475,
-1
+
+
262, 1157, 983, 880, 802, 678, 661 cm ; MS (EI): m/z 358 [M] ; HRMS (EI-TOF): m/z [M]
Calculated for C18
25 3
H F SSi: 358.1395; Found: 358.1388.
4
4
.5. Transformation of 3r
.5.1. (4-Bromophenyl)(1,1-difluoroprop-2-yn-1-yl)sulfane (3t). To a 25 mL Schlenk tube equipped
with a magnetic stir bar were added 3r (1.26 g, 3 mmol, 1.0 equiv) and THF (10 mL) under N . TBAF
2
o
(
1.0 M in THF, 3.6 mL 3.6 mmol, 1.2 equiv) was then added dropwise at -78 C. After the reaction
o
mixture was stirred at -78 C for 4 h, it was quenched with saturated aqueous NH
4
Cl. The resulting
SO ,
mixture was extracted with EtOAc. The combined organic layers were dried over anhydrous Na
2
4
1
8

filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (n-
1
hexane) to afford terminal alkyne 3t (457.8 mg, 58%) as a colorless oil. H NMR (400 MHz, CDCl
3
) δ
) δ ppm -60.70 (d, J = 4.3
) δ ppm 136.9, 131.4, 124.6, 124.1 (t, J = 1.8 Hz), 115.3 (t, J = 268.3
Hz), 77.8 (t, J = 6.1 Hz), 73.6 (t, J = 40.3 Hz); IR (thin film) ν 3300, 2142, 1566, 1473, 1388, 1147, 973,
19
ppm 7.45-7.39 (m, 4H), 2.93 (t, J = 4.4 Hz, 1H); F NMR (376 MHz, CDCl
3
1
3
Hz); C NMR (101 MHz, CDCl
3
-
1
+
+
8
2
17, 681 cm ; MS (EI): m/z 262 [M] ; HRMS (EI-TOF): m/z [M] Calculated for C
9
H
5
BrF S:
2
61.9258; Found: 261.9256.
4
.5.2. (3-Bromo-1,1-difluoroprop-2-yn-1-yl)(4-bromophenyl)sulfane (3u). To a stirred mixture of 3t
(3.8 mg,
.02 mmol, 0.1 equiv.) followed by NBS (42.8 mg, 0.24 mmol, 1.2 equiv.). The reaction mixture was
Cl was added and the mixture was
O, washed with brine, dried over anhydrous Na SO , and concentrated under reduced
pressure. The residue was purified by flash chromatography (n-hexane) to afford 3u (56.8 mg, 83%
(52.6 mg, 0.2 mmol, 1.0 equiv.) in acetone (1.0 mL) at room temperature was added AgNO
3
0
stirred at room temperature for 18 hours. Saturated aqueous NH
4
extracted with Et
2
2
4
1
19
yield) as a yellow oil. H NMR (400 MHz, CDCl
3
) δ ppm 7.47-7.39 (m, 4H); F NMR (376 MHz,
) δ ppm -59.21 (s); C NMR (101 MHz, CDCl ) δ ppm 137.0, 131.5, 124.7, 124.2 (t, J = 1.8 Hz),
15.7 (t, J = 268.7 Hz), 71.0 (t, J = 41.8 Hz), 55.1 (t, J = 8.1 Hz); IR (thin film) ν 2214, 1472, 1170,
1
3
CDCl
3
3
1
1
-1
+
+
035, 1012, 981, 817, 763, 731 cm ; MS (EI): m/z 340 [M] ; HRMS (EI-TOF): m/z [M] Calculated
for C
9
H
4
Br S: 339.8363; Found: 339.8357.
2 2
F
4
.5.3. (4-Bromophenyl)(1,1-difluoroallyl)sulfane (4). A mixture of Pd/CaCO
mg, 0.05 mmol, 25 mol%) and 3t (0.2 mmol, 52.6 mg, 1.0 equiv.) in pyridine (5.0 mL) was stirred
under H atmosphere at room temperature for 24 h. The reaction mixture was filtered by a short silica
gel column. The filtrate was washed with brine, dried over anhydrous Na SO and concentrated under
3
(20.0 mg), quinoline (6.4
2
2
4
reduced pressure. The residue was purified by flash chromatography (n-hexane) to afford terminal
1
alkene 4 (45.1 mg, 85% yield) as a colorless oil. H NMR (400 MHz, CDCl
3
) δ ppm 7.48-7.30 (m, 4H),
1
9
6
.07-5.81 (m, 1H), 5.57 (dt, J = 17.2, 2.3 Hz, 1H), 5.39 (d, J = 10.8 Hz, 1H); F NMR (376 MHz,
1
9

1
3
CDCl
3
) δ ppm -73.69 (dd, J = 9.8, 2.5 Hz); C NMR (101 MHz, CDCl ) δ ppm 136.7, 131.2, 130.7 (t, J
3
=
26.6 Hz), 125.1 (t, J = 1.6 Hz), 124.3 (t, J = 276.8 Hz), 123.8, 120.2 (t, J = 7.5 Hz); IR (thin film) ν
-1
+
2
924, 1566, 1473, 1414, 1258, 1201, 962, 816, 732 cm ; MS (EI): m/z 264 [M] ; HRMS (EI-TOF): m/z
+
[
M] Calculated for C
9
H
7
BrF S: 263.9414; Found: 263.9410.
2
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.
Acknowledgement
We thank National Natural Science Foundation of China (21421002, 21991211) and the Strategic
Priority Research Program of the Chinese Academy of Sciences (XDB20000000) for funding this work.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j. jfluchem.xxxx.xx.xxx.
2
0

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