Synthesis of 2-aryl-1,1-difluoro-1,3-enynes via consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl p-toluenesulfonate

Article abstract of DOI:10.1016/j.jfluchem.2014.07.007

Alkynylation reaction of 2,2-difluoro-1-iodoethenyl p-toluenesulfonate 1 with alkynyltributylstannanes in the presence of 10 mol% Pd(PPh₃)₄ and 10 mol% CuI in THF at reflux temperature for 3 h provided the corresponding 1,1-difluoro-

Full text of DOI:10.1016/j.jfluchem.2014.07.007

Journal of Fluorine Chemistry 167 (2014) 166–171
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of 2-aryl-1,1-difluoro-1,3-enynes via consecutive
cross-coupling reactions of 2,2-difluoro-1-iodoethenyl
p-toluenesulfonate
*
Ju Hee Kim, Ye Rim Jeong, Sung Lan Jeon, In Howa Jeong
Department of Chemistry, Yonsei University, Wonju 220-710, South Korea
A R T I C L E I N F O
A B S T R A C T
Article history:
Alkynylation reaction of 2,2-difluoro-1-iodoethenyl p-toluenesulfonate 1 with alkynyltributylstannanes
in the presence of 10 mol% Pd(PPh3)4 and 10 mol% CuI in THF at reflux temperature for 3 h provided the
corresponding 1,1-difluoro-1,3-enynyl tosylates 2 in 65–85% yields. The further arylation reaction of 2
with aryltributylstannanes in the presence of 10 mol% Pd(PPh3)2Cl2 and 3 equiv. of LiBr in THF at reflux
temperature for 8 h afforded the coupled products 3 in 32–83% yields.
Received 24 April 2014
Received in revised form 7 July 2014
Accepted 12 July 2014
Available online 19 July 2014
ß 2014 Elsevier B.V. All rights reserved.
Keywords:
2,2-Difluoro-1-iodoethenyl p-
toluenesulfonate
Alkynylation reaction
1,1-Difluoro-1,3-enynyl tosylates
Arylation reaction
1. Introduction
was achieved from the coupling reaction of (Z)-2-fluoroalkeny-
liodonium salts with 1-alkynes in the presence of Pd catalyst [17].
1,3-Enynes have received much attention because they are
valuable synthetic intermediates for the formation of multifunc-
tional molecules [1–4] and natural products [5,6] in organic
synthesis. Especially, fluorinated 1,3-enynes would be important
building blocks for the synthesis of fluorinated compounds having
unique biological and physical properties [7–9]. Although various
methods for the preparation of nonfluorinated 1,3-enynes have
been well documented in the previous literatures [10], the
preparation of fluorinated 1,3-enynes has been quite limited
and most of them related to the synthesis of monofluorinated or
1,2-difluorinated 1,3-enynes. An efficient approach to fluorinated
1,3-enynes is the palladium-catalyzed coupling reaction of
fluorinated vinyl iodides (bromides) with terminal alkyl- and
phenyl-substituted alkynes in the presence of cuprous iodides and
base. Burton et al. prepared 1,2-difluoro-1,3-enynes in good yields
from the direct coupling of substituted fluorinated vinyl iodides
with 1-alkynes via this method [11,12]. Monofluorinated 1,3-
enynes were also prepared in a similar manner [13–16]. Highly
stereoselective synthesis of monofluorinated conjugated enynes
Hammond et al. prepared monofluorinated conjugated enynes in
high yields via Wadsworth–Horner–Emmons olefination of a
fluorine-containing building block TIPS-fluoropropargylphospho-
nate with aldehydes and ketones [18]. In contrast to the synthesis
of monofluorinated or 1,2-difluorinated 1,3-enynes, the synthesis
of 1,1-difluoro-1,3-enyne derivatives has been quite limited and
thus only several methods were reported. Burton et al. reported
that 1,1-difluoro-2-phenyl-1,3-enynes were synthesized in low
yield via the hydrolysis of the trifluoromethylated allenic
phosphonium salt [19]. 1,1-Difluoro-1,3-enynes were also pre-
pared from the direct coupling reactions of 1,1-difluorovinyl
iodides with alkynylzinc chloride in the presence of Pd catalyst
[20]. Ichikawa et al. synthesized 2-alkylated 1,1-difluoro-1,3-
enynes via the coupling reaction of 1-alkyl-2,2-difluorovinylbor-
anes with 1-halo-1-alkynes in the presence of cuprous iodides, but
2-phenylated 1,1-difluoro-1,3-enynes can’t be prepared from this
method [21]. Recently, we reported an efficient method for the
preparation of 2-phenyl-1,1-difluoro-1,3-enynes from the cross-
coupling reaction of 2,2-difluoro-1-phenylethenylstannane with
alkynyl iodides in the presence of catalytic amount of Pd(PPh3)4
and CuI [22]. However, the previous methods still have some
limitations such as tedius procedure for the synthesis of starting
material and lack of generality. Herein, we wish to report a general
*
Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763 4323.
E-mail address: jeongih@yonsei.ac.kr (I.H. Jeong).
http://dx.doi.org/10.1016/j.jfluchem.2014.07.007
0022-1139/ß 2014 Elsevier B.V. All rights reserved.

J.H. Kim et al. / Journal of Fluorine Chemistry 167 (2014) 166–171
167
and straightforward preparation of 2-aryl-1,1-difluoro-1,3-enynes
via the consecutive coupling reactions of 2,2-difluoro-1-iodoethe-
nyl p-toluenesulfonate 1, which can be easily prepared from the
2,2,2-trifluoroethyl p-toluenesulfonate, with alkynyl iodides and
arylstannanes in the presence of Pd catalysis. Recently, we
prepared the starting material 1 in 80 yield from the reaction of
commercially available 2,2,2-trifluoroethyl p-toluenesulfonate
with 2 equiv. of LDA followed by treatment with iodine at low
temperature [23].
were summarized in Table 1. The use of either Pd(PPh3)4 or CuI in
this reaction did not proceed at all. We also performed the
Sonogashira reaction of 1 with phenylethyne in the presence of
Pd(PPh3)2Cl2, CuI and triethylamine in DMF at 80 8C for 3 h, but the
desired product 2a was obtained in 42% yield.
Since we developed the method for the preparation of 1,1-
diaryl-2,2-difluoroethenes via the cross-coupling reaction of 2,2-
difluoro-1-arylethenyl tosylate with arylstannane reagents in
recent years [24], we investigated the coupling reaction of 1,3-
enynyl tosylates 2 with arylstannane reagents. When 2a was
treated with phenyltributylstannane (1.5 equiv.) in the presence of
Pd(PPh3)4 (10 mol%) and LiBr (3 equiv.) in DMF at 80 8C for 5 h, the
coupled product 3a was not obtained, which result is different
from the coupling reaction of 2,2-difluoro-1-arylethenyl tosylate
with phenyltributylstannane. However, the use of THF as a solvent
in this reaction caused the formation of the desired product.
Therefore, 2a was reacted with phenyltributyl-stannane in the
presence of 10 mol% Pd(PPh3)4 and 3 equiv. LiBr in THF at reflux for
7 h to afford the coupled product 3a in 30% yield. The longer
reaction time in this reaction resulted in the formation of 3a in
lower yield. A couple of catalysts was examined to improve the
yield of 3a. The use of Pd(CH3CN)2Cl2 decreased the yield of 3a, but
the coupling reaction was activated by using Pd(PPh3)2Cl2, in
which 3a was obtained in 72% yield. Addition of X-Phos ligand did
not cause to increase the yield of 3a. The results of the optimization
for the reaction of 2a with phenyltributylstannane were summa-
rized in Table 2. We also performed the Sonogashira reaction of 2a
2. Results and discussion
First, we tried the carbon-carbon bond formation between iodo
site of 1 and alkynylstannane reagents in the presence of catalyst to
afford 1,1-difluoro-1,3-enynyl tosylate 2. The use of Pd(PPh3)4 and
CuI co-catalyst afforded the high yield of the coupled product 2.
Therefore, the reaction of 1 with phenylethynylstannane reagent in
the presence of 10 mol% Pd(PPh3)4 and 10 mol% CuI in THF at reflux
for 3 h provided the enynyl tosylate 2a in 83% yield. The coupled
product between tosylate site of 1 and alkynylstannane reagent
was not observed at all. The reactions of 1 with a variety of
arylethynylstannanes such as phenylethynylstannane having
electron-withdrawing group as well as electron-donating group
on the benzene ring, alkylethynylstannane and trialkylsilylethy-
nylstannane under the same reaction condition gave the corre-
sponding 1,3-enynyl tosylate 2b–2i in 65–85% yields. The results of
the coupling reaction between 1 and alkynylstannane reagents
Table 1
The coupling reaction of 1 with alkynylstannane reagents.
F
F
OTs
F
F
OTs
Pd(PPh3)4(10 mol%) /CuI(10 mol%)
THF, reflux, 3 h
+
Bu3Sn
R
.
C
C
I
1
2
R
Compound
R
Yield (%)a
2a
2b
2c
2d
2e
2f
C6H5
83
72
65
70
65
79
73
80
85
p-CH3C6H4
3,5-(CF3)3C6H3
p-CH3OC6H4
o-CH3OC6H4
n-C4H9
2g
2h
2i
n-C6H13
TIPS
TMS
a
Isolated yield.
Table 2
The optimization for the coupling reaction of 2a with phenyltributylstannane.
F
OTs
F
F
Ph
C
Pd catalyst (10 mol%) /LiBr (3 equiv)
Solvent, T oC, t h
+
PhSnBu3
F
.
C
C
C
2a
3a
Ph
Ph
Entry
Pd Catalyst
Pd(PPh3)4
Solvent
T (8C)
t (h)
Yield (%)a
1
2
3
4
5
6
7
DMF
DMF
THF
THF
THF
THF
THF
60
5
5
0
0
Pd(PPh3)4
80
Pd(PPh3)4
reflux
reflux
reflux
reflux
reflux
7
30
10
72
55
20
Pd(PPh3)4
17
7
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
b
7
Pd(CH3CN)2Cl2
7
a
Isolated yield.
b
X-Phos (20 mol%) as a ligand was added.

168
J.H. Kim et al. / Journal of Fluorine Chemistry 167 (2014) 166–171
Table 3
The coupling reaction of 2a with aryltributylstannane.
R
F
F
F
F
OTs
R
Pd(PPh3)2Cl2(10 mol%) /LiBr(3 equiv)
THF, reflux, 7 h
SnBu3
+
.
C
C
C
C
Ph
3
2a
Ph
Compound
R
Yield (%)a
3a
3b
3c
3d
3e
3f
H
72
52
47
83
81
33
73
67
75
69
p-CH3
m-CH3
p-Cl
m-Cl
m-OCH3
p-F
3g
3h
3i
m-F
p-CF3
m-CF3
3j
a
Isolated yield.
with phenylethyne in the presence of Pd(PPh3)2Cl2, CuI and
triethylamine in DMF at 80 8C for 3 h, but the desired product 3a
was not obtained. The Suzuki-Miyaura reaction of 2a with
phenylboronic acid in the presence of Pd(OAc)2, Pd(PPh3)2Cl2 or
Pd(CH3CN)2Cl2, and base such as K2CO3, Na2CO3, Cs2CO3, or K3PO4
provided the homo-coupled product of phenylboronic acid instead
of 3a.
Optimized reaction condition was applied to prepare a variety
of the coupled products 3. Therefore, reactions of 2a with
phenyltributylstannanes substituted with the methyl, chloro,
methoxy, fluoro and trifluoromethyl group at ortho-, meta- or
para-position of the benzene ring in the presence of 10 mol%
Pd(PPh3)2Cl2 and 3 equiv. LiBr in THF at reflux for 7 h resulted in
the formation of 3b–3k in 32–83% yields. The coupling reaction
with phenyltributylstannanes having the methyl or methoxy
group at meta- or para position of the benzene ring gave relatively
lower yields. However, phenyltributylstannanes having electron-
withdrawing group such as fluoro or trifluoromethyl group
provided the coupled product in high yields in this reaction. The
results of these reactions are summarized in Table 3.
negative. All chemical shifts (d) are expressed in parts per million
and coupling constant (J) are given in Hertz. Mass spectra were
obtained by using Agilent Technologies 6890N GC/5973 Network
MSD (EI, 70 eV). Elemental analysis data were obtained by using
EA1110 elemental analyzer. Melting points were determined in
open capillary tubes and are uncorrected.
Commercially available reagents were purchased from Aldrich,
Lancaster, Tokyo Kasei and Fluorochem. All solvents were dried by
general purification method. Flash chromatography was per-
formed on 40–60
mm silica gel (230–400 mesh).
4.1. General procedure for the preparation of 1,1-difluoro-1,3-enyn-
2-yl p-toluenesulfonates 2
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with Pd(PPh3)4 (10 mol%), CuI (10 mol%)
and 3 mL of THF. The solution of 2,2-difluoro-1-iodoethenyl p-
toluenesulfonate (0.300 g, 0.833 mmol) and alkynyltributylstan-
nane (1.0 mmol) dissolved in 3 mL of THF was added into the
reaction mixture. After the reaction mixture was refluxed for 3 h
and then cooled to room temperature, the mixture was quenched
with water. The reaction mixture was extracted with ether twice,
dried over anhydrous MgSO4 and chromatographed on SiO2
column. Elution with n-hexane and ethyl acetate (4:1) provided
1,1-difluoro-1,3-enyn-2-yl p-toluenesulfonates 2.
3. Conclusion
In summary, we have developed a general method for the
preparation 2,2-difluoro-1-alkynylethenyl tosylate 2 via the Stille
coupling reaction between 2,2-difluoro-1-iodoethenyl tosylate 1
with alkynylstannane reagents. Further direct coupling reaction at
the tosylate site of 2 with arylstannane reagents via the Stille type
reaction afforded the 2-aryl-1,1-difluoro-1,3-enynes 3 in good
yields. This method provided an efficient and straightforward
preparation of 2-aryl-1,1-difluoro-1,3-enynes via the consecutive
Stille cross-coupling reaction at two iodo and tosyl elecrophilic
sites of 1. The coupled products 3 are potentially reactive species
toward the nucleophiles to give monofluorinated enynes and also
toward the electrophiles to give fluorinated enones. The further
synthetic utilities of 3 will be described in the future paper.
4.1.1. 1,1-Difluoro-4-phenylbut-1-en-3-yn-2-yl p-toluenesulfonate
(2a)
2a was prepared in 83% yield (0.231 g) according to the general
procedure. 2a: yellow solid; mp 70–72 8C; 1H NMR (CDCl3)
d
7.90
(d, J = 8.4 Hz, 2H), 7.35–7.20 (m, 5H), 7.18 (d, J = 8.4 Hz, 2H), 2.38 (s,
3H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
À81.79 (d,
160.3
J = 11.3 Hz, 1F), À94.54 (d, J = 11.3 Hz, 1F); 13C NMR (CDCl3)
d
(dd, J = 303, 295 Hz), 146.0, 132.5, 131.3, 129.8, 129.5, 128.8, 128.3,
120.9, 100.4–99.6 (m), 74.6 (dd, J = 9, 3 Hz), 21.6; MS, m/z (relative
intensity) 334 (M+, 2), 155 (25), 139 (6), 129 (100), 101 (11), 91
(53), 75 (16), 65 (20), 51 (6). Anal. Calcd for C17H12F2O3S: C, 61.07;
H, 3.62. Found: C, 59.89; H, 3.60.
4. Experimental
1H and 13C NMR spectra were recorded on a 400 MHz Bruker
AVANCEII++ NMR spectrometer with tetramethylsilane (TMS) as an
internal standard and 19F NMR spectra were also recorded on a
400 MHz Bruker AVANCEII++ NMR spectrometer with C6H5CF3
(À63.72 ppm from CFCl3) as an internal standard and the upfield as
4.1.2. 1,1-Difluoro-4-p-tolylbut-1-en-3-yn-2-yl p-toluenesulfonate
(2b)
2b was prepared in 72% yield (0.209 g) according to the general
procedure. 2b: yellow oil; 1H NMR (CDCl3)
d 7.87 (d, J = 8.4 Hz, 2H),

J.H. Kim et al. / Journal of Fluorine Chemistry 167 (2014) 166–171
169
7.31 (d, J = 8.4 Hz, 2H), 7.10–7.03 (m, 4H), 2.37 (s, 3H), 2.33 (s, 3H);
5H), 0.92 (m, 5H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
19F NMR (CDCl3, internal standard C6H5CF3)
d
À82.53 (d,
À84.10 (d, J = 18.8 Hz, 1F), À97.78 (d, J = 18.8 Hz, 1F); 13C NMR
J = 11.3 Hz, 1F), À95.13 (d, J = 11.3 Hz, 1F); 13C NMR (CDCl3)
d
(CDCl3)d160.6 (dd, J = 301, 293 Hz), 145.9, 133.0, 129.9, 128.9, 102.8
160.3 (dd, J = 303, 295 Hz), 146.1, 140.0, 132.6, 131.3, 129.9, 129.1,
128.9, 128.3, 117.8, 100.7–99.8 (m), 74.0 (dd, J = 9, 3 Hz), 21.6,
21.5; MS, m/z (relative intensity) 348 (M+, 5), 155 (26), 143 (100),
115 (8), 91 (55), 65 (13). Anal. Calcd for C18H14F2O3S: C, 62.06; H,
4.05. Found: C, 61.79; H, 4.01.
(d, J = 9, 5 Hz), 100.2 (dd, J = 48, 39 Hz), 66.7 (dd, J = 9, 3 Hz), 31.4,
28.5, 27.9, 22.6, 21.8, 19.5, 14.1; MS, m/z (relative intensity) 342 (M+,
1), 155 (100), 139 (20), 137 (23), 91(85), 79(3), 65 (8). Anal. Calcd for
C17H20F2O3S: C, 59.63; H, 5.89. Found: C, 59.45; H, 5.85.
4.1.8. 1,1-Difluoro-4-(triisopropylsilyl)but-1-en-3-yn-2-yl p-
toluenesulfonate (2h)
4.1.3. 4-(3,5-Bis(trifluoromethyl)phenyl)-1,1-difluorobut-1-en-3-yn-
2-yl p-toluenesulfonate (2c)
2h was prepared in 80% yield (0.276 g) according to the general
2c was prepared in 65% yield (0.254 g) according to the general
procedure. 2h: colorless oil; 1H NMR (CDCl3)
d
7.85 (d, J = 8.4 Hz,
procedure. 2c: yellow oil; 1H NMR (CDCl3)
d
7.92 (d, J = 8.2 Hz, 2H),
2H), 7.33 (d, J = 8.4 Hz, 2H), 2.45 (s, 3H), 0.98 (d, J = 1.6 Hz, 18H),
7.84 (s, 1H), 7.62 (s, 2H), 7.38 (d, J = 8.2 Hz, 2H), 2.41 (s, 3H); 19F
0.95–0.90 (m, 3H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
NMR (CDCl3, internal standard C6H5CF3)
d
À64.16 (s, 6F), À78.63
À80.70 (d, J = 11.3 Hz, 1F), À94.49 (d, J = 11.3 Hz, 1F); 13C NMR
(d, J = 7.5 Hz, 1F), À91.90 (d, J = 7.5 Hz, 1F); 13C NMR (CDCl3)
d
(CDCl3) d 161.7 (dd, J = 302, 293 Hz), 146.0, 132.8, 130.1, 128.8,
161.1 (dd, J = 303, 295 Hz), 146.7, 132.7, 132.5, 132.2, 131.3, 130.1,
129.2, 122.5 (q, J = 290 Hz), 100.6–99.5 (m), 78.3 (dd, J = 9, 3 Hz),
21.7; MS, m/z (relative intensity) 470 (M+, 1), 451 (4), 265 (83), 218
(10), 187 (12), 168 (8), 155 (90), 139 (15), 91 (100), 65 (21). Anal.
Calcd for C19H10F8O3S: C, 48.52; H, 2.14. Found: C, 48.46; H, 2.12.
105.0 (d, J = 9, 5 Hz), 100.1 (dd, J = 47, 28 Hz), 91.3 (dd, J = 9, 3 Hz),
21.9, 18.5, 11.1; MS, m/z (relative intensity) 414 (M+, 1), 371 (100),
269 (45), 261 (18), 205 (14), 155 (15), 139 (19), 91 (28), 77 (5), 65
(3). Anal. Calcd for C20H28F2O3SSi: C, 57.94; H, 6.81. Found: C,
57.72; H, 6.77.
4.1.4. 1,1-Difluoro-4-(4-methoxyphenyl)but-1-en-3-yn-2-yl p-
toluenesulfonate (2d)
4.1.9. 1,1-Difluoro-4-(trimethylsilyl)but-1-en-3-yn-2-yl p-
toluenesulfonate (2i)
2d was prepared in 70% yield (0.212 g) according to the general
2i was prepared in 85% yield (0.234 g) according to the general
procedure. 2d: yellow oil; 1H NMR (CDCl3)
d
7.89 (d, J = 8.2 Hz, 2H),
procedure. 2i: yellow oil; 1H NMR (CDCl3)
d
7.86 (d, J = 8.4 Hz, 2H),
7.35 (d, J = 8.4 Hz, 2H), 2.47 (s, 3H), 0.07 (s, 9H); 19F NMR (CDCl3,
internal standard C6H5CF3)
À80.63 (d, J = 11.3 Hz, 1F), À94.00 (d,
J = 11.3 Hz, 1F); 13C NMR (CDCl3)
161.5 (dd, J = 302, 293 Hz),
7.32 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 8.4 Hz,
2H), 3.81 (s, 3H), 2.39 (s, 3H); 19F NMR (CDCl3, internal standard
d
C6H5CF3)
d
À82.65 (d, J = 11.3 Hz, 1F), À95.29 (d, J = 11.3 Hz, 1F);
160.4 (dd, J = 303, 295 Hz), 146.1, 135.5, 133.6,
d
13C NMR (CDCl3)
d
146.1, 132.7, 130.0, 130.0, 107.9 (d, J = 9, 5 Hz), 100.1 (dd, J = 47,
28 Hz), 89.1 (dd, J = 9, 3 Hz), 21.8, À0.7; MS, m/z (relative intensity)
330 (M+, 1), 155 (50), 139 (17), 125 (45), 91 (100), 73 (20), 65 (30).
Anal. Calcd for C14H16F2O3SSi: C, 50.89; H, 4.88. Found: C, 50.78; H,
4.86.
133.1, 132.9, 130.2, 129.8, 129.1, 100.6–99.8 (m), 73.6 (dd, J = 9,
3 Hz), 55.8, 22.0; MS, m/z (relative intensity) 364 (M+, 15), 159
(100), 139 (7), 116 (8), 91 (31), 65 (7). Anal. Calcd for C18H14F2O4S:
C, 59.34; H, 3.87. Found: C, 59.21; H, 3.84.
4.1.5. 1,1-Difluoro-4-(2-methoxyphenyl)but-1-en-3-yn-2-yl p-
toluenesulfonate (2e)
4.2. General procedure for the preparation of 2-aryl-1,1-difluoro-4-
phenylbut-1-en-3-ynes 3
2e was prepared in 70% yield (0.197 g) according to the general
procedure. 2e: yellow oil; 1H NMR (CDCl3)
d
7.90 (d, J = 8.2 Hz, 2H),
A 10 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with Pd(PPh3)2Cl2 (10 mol%), LiBr
(0.078 g, 0.90 mmol) and 1 mL of THF. The solution of 2a (0.100 g,
0.30 mmol) and aryltributylstannane (0.45 mmol) dissolved in
2 mL of THF was added into the reaction mixture. After the reaction
mixture was refluxed for 7 h and then cooled to room temperature,
the mixture was quenched with water. The reaction mixture was
extracted with ether twice, dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with n-hexane and
ethyl acetate (20:1) provided 2-aryl-1,1-difluoro-4-phenylbut-1-
en-3-ynes 3.
7.38–7.26 (m, 3H), 7.08–7.06 (m, 1H), 6.88–6.83 (m, 2H), 3.83 (s,
3H), 2.36 (s, 3H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
À82.53 (d, J = 11.3 Hz, 1F), À94.63 (d, J = 11.3 Hz, 1F); 13C NMR
(CDCl3)
d 160.3 (dd, J = 306, 295 Hz), 146.0, 133.6, 132.8, 131.3,
129.9, 129.1, 120.5, 110.9, 110.5, 100.8–99.5 (m), 78.5 (dd, J = 9,
3 Hz), 55.9, 21.8; MS, m/z (relative intensity) 364 (M+, 15), 159
(100), 155 (30), 139 (17), 131 (27), 115 (38), 91 (94), 77 (28), 65
(15). Anal. Calcd for C18H14F2O4S: C, 59.34; H, 3.87. Found: C,
59.18; H, 3.82.
4.1.6. 1,1-Difluorooct-1-en-3-yn-2-yl p-toluenesulfonate (2f)
2f was prepared in 79% yield (0.207 g) according to the general
procedure. 2f: yellow oil; 1H NMR (CDCl3)
d
7.86 (d, J = 8.4 Hz, 2H),
4.2.1. 1,1-Difluoro-2,4-diphenylbut-1-en-3-yne (3a)
7.37 (d, J = 8.4 Hz, 2H), 2.46 (s, 3H), 2.16 (t, J = 6.8 Hz, 2H), 1.43–
1.26 (m, 4H), 0.87 (t, J = 6.8 Hz, 3H); 19F NMR (CDCl3, internal
3a was prepared in 72% yield (0.052 g) according to the general
procedure. 3a: yellow oil; 1H NMR (CDCl3)
d
7.62–7.58 (m, 4H),
7.52–7.38 (m, 3H), 7.35–7.29 (m, 3H); 19F NMR (CDCl3, internal
standard C6H5CF3)
À75.89 (d, J = 3.8 Hz, 1F), À80.47 (d, J = 3.8 Hz,
1F); 13C NMR (CDCl3)
159.1 (dd, J = 301, 296 Hz), 141.2, 131.5,
standard C6H5CF3)
d
À84.14 (d, J = 18.8 Hz, 1F), À97.76 (d,
160.5 (dd, J = 300, 293 Hz),
J = 18.8 Hz, 1F); 13C NMR (CDCl3)
d
d
145.8, 132.7, 130.1, 129.7, 128.7, 128.4, 102.8 (d, J = 9, 5 Hz), 100.0
(dd, J = 48, 39 Hz), 66.4 (dd, J = 9, 3 Hz), 29.8, 21.8, 21.6, 19.0, 13.4;
MS, m/z (relative intensity) 314 (M+, 1), 155 (70), 139 (17), 109
(40), 91 (100), 79 (10), 65 (20). Anal. Calcd for C15H16F2O3S: C,
57.31; H, 5.13. Found: C, 57.17; H, 5.08.
d
130.7, 128.6, 128.4, 127.9, 127.2, 122.7, 94.3 (dd, J = 8, 4 Hz), 82.4
(dd, J = 28, 20 Hz), 80.4 (dd, J = 8, 4 Hz); MS, m/z (relative intensity)
240 (M+, 100), 220 (21), 189 (43), 163 (7), 150 (3), 87 (3), 63 (3), 51
(4). Anal. Calcd for C16H10F2: C, 79.99; H, 4.20. Found: C, 79.83; H,
4.18.
4.1.7. 1,1-Difluorodec-1-en-3-yn-2-yl p-toluenesulfonate (2g)
2g was prepared in 73% yield (0.208 g) according to the general
4.2.2. 1,1-Difluoro-4-phenyl-2-p-tolylbut-1-en-3-yne (3b)
procedure. 2g: colorlessoil;1H NMR (CDCl3)
d
7.45(d, J = 8.4 Hz, 2H),
3b was prepared in 52% yield (0.040 g) according to the general
6.85 (d, J = 8.4 Hz, 2H), 3.81 (s, 3H), 1.65–1.57 (m, 3H), 1.41–1.33 (m,
procedure. 3b: yellow oil; 1H NMR (CDCl3)
d 7.50–7.48 (m, 4H),

170
J.H. Kim et al. / Journal of Fluorine Chemistry 167 (2014) 166–171
7.35–7.32 (m, 3H), 7.21–7.19 (m, 2H), 2.36 (s, 3H); 19F NMR (CDCl3,
internal standard C6H5CF3)
À76.66 (d, J = 3.8 Hz, 1F), À81.06 (d,
J = 3.8 Hz, 1F); 13C NMR (CDCl3)
159.2 (dd, J = 300, 296 Hz), 138.0,
131.8, 129.5, 128.8, 128.6, 127.9, 127.8, 123.1, 94.4 (dd, J = 8, 4 Hz),
82.4 (dd, J = 28, 20 Hz), 80.9 (dd, J = 8, 4 Hz), 21.4; MS, m/z (relative
intensity) 254 (M+, 100), 238 (17), 233 (15), 202 (20), 189 (9), 101
(5), 91 (4). Anal. Calcd for C17H12F2: C, 80.30; H, 4.76. Found: C,
80.02; H, 4.72.
128.7, 126.8, 122.8, 115.8, 94.8 (dd, J = 8, 4 Hz), 81.9 (dd, J = 28,
20 Hz), 80.4 (dd, J = 8, 4 Hz); MS, m/z (relative intensity) 258 (M+,
100), 238 (19), 207 (76), 181 (13), 75 (10), 63 (10), 51 (12). Anal.
Calcd for C16H9F3: C, 74.42; H, 3.51. Found: C, 74.13; H, 3.45.
d
d
4.2.8. 1,1-Difluoro-2-(m-fluorophenyl)-4-phenylbut-1-en-3-yne
(3h)
3h was prepared in 67% yield (0.052 g) according to the general
procedure. 3h: yellow oil; 1H NMR (CDCl3)
d
7.52–7.50 (m, 2H),
4.2.3. 1,1-Difluoro-4-phenyl-2-m-tolylbut-1-en-3-yne (3c)
7.45–7.36 (m, 5H), 7.08–6.99 (m, 2H); 19F NMR (CDCl3, internal
3c was prepared in 47% yield (0.036 g) according to the general
standard C6H5CF3)
d
À74.43 (d, J = 3.8 Hz, 1F), À78.81 (d, J = 3.8 Hz,
procedure. 3c: yellow oil; 1H NMR (CDCl3)
d
7.51–7.50 (m, 3H),
7.41–7.27 (m, 4H), 7.14–7.12 (m, 2H), 2.39 (s, 3H); 19F NMR (CDCl3,
internal standard C6H5CF3)
À76.06 (d, J = 3.8 Hz, 1F), À80.56 (d,
J = 3.8 Hz, 1F); 13C NMR (CDCl3)
159.2 (dd, J = 300, 296 Hz), 141.5,
1F), À113.54 (m, 1F); 13C NMR (CDCl3)
d 163.0 (d, J = 244 Hz), 159.5
(dd, J = 300, 296 Hz), 133.1, 131.8, 130.3, 128.6, 123.6, 122.9, 115.0,
114.9, 114.1, 95.0 (dd, J = 8, 4 Hz), 81.2 (dd, J = 28, 20 Hz), 79.9 (dd,
J = 8, 4 Hz); MS, m/z (relative intensity) 258 (M+, 100), 238 (21), 207
(50), 181 (5), 103 (4). Anal. Calcd for C16H9F3: C, 74.42; H, 3.51.
Found: C, 74.20; H, 3.47.
d
d
138.5, 131.7, 128.9, 128.7, 128.5, 128.2, 125.2, 124.5, 122.9, 94.5
(dd, J = 8, 4 Hz), 82.5 (dd, J = 28, 20 Hz), 80.8 (dd, J = 8, 4 Hz), 21.7;
MS, m/z (relative intensity) 254 (M+, 100), 238 (16), 233 (17), 202
(19), 189 (8), 101 (5). Anal. Calcd for C17H12F2: C, 80.30; H, 4.76.
Found: C, 80.11; H, 4.73.
4.2.9. 1,1-Difluoro-2-(p-trifluoromethyl)phenyl-4-phenylbut-1-en-
3-yne (3i)
3i was prepared in 75% yield (0.069 g) according to the general
4.2.4. 2-(p-Chlorophenyl)-1,1-difluoro-4-phenylbut-1-en-3-yne (3d)
3d was prepared in 83% yield (0.068 g) according to the general
procedure. 3i: yellow oil; 1H NMR (CDCl3)
d
7.52–7.50 (m, 2H),
7.75–7.71 (m, 4H), 7.67–6.65 (m, 2H), 7.53–7.50 (m, 1H), 7.37–7.35
procedure. 3d: yellow oil; 1H NMR (CDCl3)
d
7.55–7.46 (m, 4H),
(m, 2H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
À63.85 (s,
7.41–7.34 (m, 5H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
3F), À73.53 (d, J = 3.8 Hz, 1F), À78.57 (d, J = 3.8 Hz, 1F); 13C NMR
À75.15 (d, J = 3.8 Hz, 1F), À79.74 (d, J = 3.8 Hz, 1F); 13C NMR
(CDCl3) d 159.7 (dd, J = 300, 296 Hz), 134.7, 132.2, 131.8, 130.3,
(CDCl3)
d
159.3 (dd, J = 300, 296 Hz), 137.8, 134.0, 131.8, 129.3,
129.1, 128.7, 126.6, 122.8, 95.2 (dd, J = 8, 4 Hz), 82.0 (dd, J = 28,
20 Hz), 79.6 (dd, J = 8, 4 Hz); MS, m/z (relative intensity) 308 (M+,
100), 289 (10), 257 (13), 238 (34), 189 (17), 119 (7). Anal. Calcd for
129.2, 129.0, 128.6, 122.7, 95.0 (dd, J = 8, 4 Hz), 82.0 (dd, J = 28,
20 Hz), 80.1 (dd, J = 8, 4 Hz); MS, m/z (relative intensity) 276
(M+ + 2, 34), 274 (M+, 100), 238 (37), 223 (11), 189 (40), 187 (30),
163 (10), 137 (9), 123 (9), 111 (10), 75 (11), 63 (8), 50 (9). Anal.
Calcd for C16H9ClF2: C, 69.96; H, 3.30. Found: C, 69.68; H, 3.27.
C17H9F5: C, 66.24; H, 2.94. Found: C, 66.02; H, 2.92.
4.2.10. 1,1-Difluoro-2-(m-trifluoromethyl)phenyl-4-phenylbut-1-
en-3-yne (3j)
4.2.5. 2-(m-Chlorophenyl)-1,1-difluoro-4-phenylbut-1-en-3-yne
(3e)
3j was prepared in 69% yield (0.064 g) according to the general
procedure. 3j: yellow oil; 1H NMR (CDCl3)
d
7.87–7.78 (m, 3H),
3e was prepared in 81% yield (0.067 g) according to the general
7.65–7.41 (m, 4H), 7.37–7.34 (m, 2H); 19F NMR (CDCl3, internal
procedure. 3e: yellow oil; 1H NMR (CDCl3)
d
7.52–7.50 (m, 1H),
7.48–7.41 (m, 3H), 7.36–7.28 (m, 5H); 19F NMR (CDCl3, internal
standard C6H5CF3)
À74.38 (d, J = 3.8 Hz, 1F), À78.93 (d, J = 3.8 Hz,
1F); 13C NMR (CDCl3)
159.5 (dd, J = 300, 296 Hz), 134.8, 132.7,
standard C6H5CF3)
d
À63.86 (s, 3F), À74.19 (d, J = 3.8 Hz, 1F),
À79.16 (d, J = 3.8 Hz, 1F); 13C NMR (CDCl3)
d 159.6 (dd, J = 300,
d
296 Hz), 140.8, 131.8, 131.2, 130.7, 129.8, 129.3, 128.7, 125.0,
124.8, 122. 6, 95.4 (dd, J = 8, 4 Hz), 82.1 (dd, J = 28, 20 Hz), 79.7 (dd,
J = 8, 4 Hz); MS, m/z (relative intensity) 308 (M+, 100), 289 (7), 257
(12), 238 (30), 189 (19), 119 (7). Anal. Calcd for C17H9F5: C, 66.24;
H, 2.94. Found: C, 66.10; H, 2.93.
d
131.8, 129.9, 129.0, 128.5, 128.3, 128.0, 126.1, 122.7, 95.1 (dd, J = 8,
4 Hz), 82.0 (dd, J = 28, 20 Hz), 79.8 (dd, J = 8, 4 Hz); MS, m/z
(relative intensity) 276 (M++2, 34), 274 (M+, 100), 238 (50), 189
(26), 187 (13), 137 (5), 119 (5), 95 (5). Anal. Calcd for C16H9ClF2: C,
69.96; H, 3.30. Found: C, 69.64; H, 3.26.
Acknowledgment
4.2.6. 1,1-Difluoro-2-(m-methoxyphenyl)-4-phenylbut-1-en-3-yne
(3f)
This work was supported by a Basic Research Grant (2011-
0022295) funded by the National Research Foundation.
3f was prepared in 33% yield (0.027 g) according to the general
procedure. 3f: yellow oil; 1H NMR (CDCl3)
d
7.56–7.54 (m, 2H),
References
7.39–7.33 (m, 4H), 7.26–7.21 (m, 2H), 6.92–6.90 (m, 1H), 3.87 (s,
3H); 19F NMR (CDCl3, internal standard C6H5CF3)
d
À75.50 (d,
159.5
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J = 3.8 Hz, 1F), À79.70 (d, J = 3.8 Hz, 1F); 13C NMR (CDCl3)
d
(dd, J = 300, 296 Hz), 132.2, 131.7, 129.8, 128.8, 128.6, 122.9, 120.4,
113.9, 113.8, 113.6, 94.5 (dd, J = 8, 4 Hz), 82.5 (dd, J = 28, 20 Hz),
80.6 (dd, J = 8, 4 Hz); MS, m/z (relative intensity) 270 (M+, 100), 255
(7), 227 (14), 207 (14), 176 (12). Anal. Calcd for C17H12F2O: C,
75.55; H, 4.48. Found: C, 75.28; H, 4.41.
5 (2003)
4.2.7. 1,1-Difluoro-2-(p-fluorophenyl)-4-phenylbut-1-en-3-yne (3g)
3g was prepared in 73% yield (0.057 g) according to the general
procedure. 3g: yellow oil; 1H NMR (CDCl3)
d
7.59–7.56 (m, 1H),
7.52–7.49 (m, 3H), 7.38–7.36 (m, 2H), 7.13–7.06 (m, 3H); 19F NMR
(CDCl3, internal standard C6H5CF3)
d
À76.29 (d, J = 3.8 Hz, 1F),
À80.97 (d, J = 3.8 Hz, 1F), À114.55 (m, 1F); 13C NMR (CDCl3)
d 162.5
(d, J = 247 Hz), 159.2 (dd, J = 300, 296 Hz), 136.6, 131.8, 129.8,

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