Facile synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes via stepwise coupling of 1,1-dibromo-2,2-difluoroethenes

Article abstract of DOI:10.1016/j.jfluchem.2013.06.010

Unsymmetrical 1,1-diaryl-2,2-difluoroethenes were synthesized from 1,1-dibromo-2,2-difluoroethene, which is commercially available, via the Suzuki-Miyaura coupling in a stepwise fashion. Suitable ligands for each coupling process were used to achieve selective synthesis of these diaryldifluoroethenes.

Full text of DOI:10.1016/j.jfluchem.2013.06.010

Journal of Fluorine Chemistry 155 (2013) 97–101
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Facile synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes via
stepwise coupling of 1,1-dibromo-2,2-difluoroethenes
*
Takeshi Fujita, Naoto Suzuki, Tomohiro Ichitsuka, Junji Ichikawa
Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Unsymmetrical 1,1-diaryl-2,2-difluoroethenes were synthesized from 1,1-dibromo-2,2-difluoroethene,
which is commercially available, via the Suzuki–Miyaura coupling in a stepwise fashion. Suitable ligands
for each coupling process were used to achieve selective synthesis of these diaryldifluoroethenes.
ß 2013 Elsevier B.V. All rights reserved.
Received 17 April 2013
Received in revised form 12 June 2013
Accepted 20 June 2013
Available online 10 July 2013
Keywords:
Difluoroalkene
Diarylethene
Dibromoethene
Ligand
Suzuki–Miyaura coupling
Stepwise arylation
1. Introduction
type of selective reaction requires steric and/or electronic effects of
vinylic substituents [8]. Although the monoarylation of symmetric
1,1-Diaryl-2,2-difluoroethenes are an important class of gem-
difluoroalkenes, which have the potential to be used for a wide
range of purposes, including functional materials and medicines
such as photoreceptors [1], anticancer drugs [2], and dermatologi-
cal agents [3]. These compounds are also expected to be
bioisosteres of biologically active diarylketones [4]. Despite their
versatility, the supply of 1,1-diaryl-2,2-difluoroethenes has been
limited because of difficulties involved in synthesizing them
(Scheme 1) [5,6]. Conventional synthetic methods, especially for
unsymmetrically disubstituted 1,1-diaryl-2,2-difluoroethenes,
have mostly required difluorovinylidene species to be synthesized
as key intermediates, bearing both a metal functional group and a
gem-dichloroethenes has been reported, the low reactivities of
their chlorine substituents might prevent a second arylation
toward diarylated ethenes. Using highly reactive coupling partners
of the arylating agents and/or vinyl halides (or pseudohalides)
would easily induce double arylation, leading to undesirable
symmetrical byproducts. Therefore, the selective synthesis of
unsymmetrically disubstituted 1,1-diaryl-2,2-difluoroethenes is a
significant challenge.
To solve these synthetic problems, we sought to find an
appropriate ligand for each coupling step, preventing the forma-
tion of symmetrical 1,1-diaryl-2,2-difluoroethenes 3. We eventu-
ally achieved the selective synthesis of unsymmetrical 1,1-diaryl-
2,2-difluoroethenes 4 by choosing ligands to control the reactiv-
ities in the first and second arylations of 1,1-dibromo-2,2-
difluoroethene (1), which is commercially available (Scheme 2) [9].
halogen (or pseudohalogen) substituent at the carbon
b to the
fluorine substituents [6]. This is due to selective introduction of
two different aryl groups. The preparation of such intermediates is
troublesome and requires extra synthetic steps.
A straightforward synthesis of unsymmetrical 1,1-diaryl-2,2-
difluoroethenes might be achieved simply with two reactivity-
controlled coupling reactions, starting from 1,1-difluoro-2,2-
dihaloethenes. However, there are only a few examples of the
monoarylation of symmetric gem-dihaloethenes [7], because this
2. Results and discussion
2.1. The first coupling: selective synthesis of 1-aryl-1-bromo-2,2-
difluoroethene 2 from 1,1-dibromo-2,2-difluoroethene (1)
To synthesize unsymmetrically disubstituted 1,1-diaryl-2,2-
difluoroethenes 4, we first sought suitable conditions for selective
monoarylation in the Suzuki–Miyaura coupling between 1,1-
dibromo-2,2-difluoroethene (1) and phenylboronic acid, using
* Corresponding author. Tel.: +81 29 853 4237; fax: +81 29 853 4237.
E-mail addresses: junji@chem.tsukuba.ac.jp, junjii@me.com (J. Ichikawa).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.06.010

98
T. Fujita et al. / Journal of Fluorine Chemistry 155 (2013) 97–101
X
F
X
cat. Pd
Ar1X
cat. Pd
Ar2M
X
X
Ar2
Ar1
F
F
F
F
M
Ar1
F
F
F
X
M = Zn(II), Sn(IV)
X = Br, I, OTs
F3C
Scheme 1. Conventional synthesis of 1,1-diaryl-2,2-difluoroethenes.
Pd / Ligand 1
Ar1B(OH)2
Pd / Ligand 2
Ar2B(OH)2
highest yield of 2a in a short reaction time (Entry 11). Finally,
we found that the optimum dioxane/water ratio was 2:1 (Entry
16), which gave, almost exclusively, bromodifluorostyrene 2a
in 80% yield.
Once the optimal conditions had been determined, we the
scope of the substrate (Table 2). Monoarylation with several para-
functionalized (Me, Ph, OMe, and F) phenylboronic acids was
successfully achieved, providing bromodifluorostyrenes 2a–2e. To
the best of our knowledge, this is the first example of the selective
monoarylation of symmetrical gem-dibromoalkenes.
Br
Br
Ar2
Ar1
F
F
F
Br
Ar1
F
F
F
F
1
2
4
Ar1
Ar1
F
2.2. The second coupling: synthesis of unsymmetrically substituted
1,1-diaryl-2,2-difluoroethenes 4 from 1-aryl-1-bromo-2,2-
difluoroethenes 2
3
Scheme 2. Strategy for the synthesis of unsymmetrical 1,1-diaryl-2,2-
difluoroethenes 4 via stepwise coupling of 1,1-dibromo-2,2-difluoroethene (1).
The ligand used for the second coupling in the synthesis of
unsymmetrically disubstituted 1,1-diaryl-2,2-difluoroethenes 4
was examined next, and the ligands were screened in the Suzuki–
Miyaura coupling of monoarylated bromodifluorostyrene 2c
with 4-fluorophenylboronic acid, at higher temperatures than in
the first step (Table 3). The second coupling proceeded most
effectively using triphenylphosphine, yielding 1,1-diaryl-2,2-
difluoroethenes 4c in 72% yield (Entry 1). The low yield obtained
by using dppm indicated that dppm, although highly suitable for
the first coupling, effectively suppressed the second coupling
(Entry 4).
cesium fluoride as a base (Table 1). The choice of ligands used with
Pd2dba3ꢀCHCl3 (dba = dibenzylideneacetone) was found to be
critical for the yield of the monoarylated product, 1-bromo-1-
phenyl-2,2-difluoroethene (2a, Entries 1–8). Among the ligands
that were screened, 1,1-bis(diphenylphosphino)methane
(dppm) gave the highest yield of 2a (Entry 8), suppressing
the formation of the diarylated product 3a. Co-solvents used
with water (Entries 9–14) at different ratios (Entries 15–16)
were subsequently examined. Ether-type typically gave good
yield and selectivity of 2a (Entries 9–11), and dioxane gave the
Table 1
Effects of the ligand and solvent used in the first Suzuki–Miyaura coupling.
Pd2dba3•CHCl3 (0.5 mol%)
Ligand 1 (1 mol%)
PhB(OH)2 (1.0 equiv)
Br
Br
Ph
CsF (2.0 equiv)
F
F
F
+
Br
Ph
Ph
Solvent–H2O (x:y)
60 °C, Time
F
F
F
1
2a
3a
.
Entry
Ligand 1
Solvent (x:y)
Time (h)
2a (%)a
3a (%)a
b
1
2
PPh3
THF (4:1)
6
6
6
6
6
6
6
6
3
3
3
3
3
3
3
3
51
–
Trace
b
P(t-Bu)3
Cy-JohnPhosb
THF (4:1)
–
3
THF (4:1)
–
–
b
4
AsPh3
THF (4:1)
24
8
Trace
5
Xantphos
dppf
THF (4:1)
12
6
THF (4:1)
40
14
54
36
49
70
10
36
23
53
80
1
7
dppb
THF (4:1)
Trace
8
dppm
dppm
dppm
dppm
dppm
dppm
dppm
dppm
dppm
THF (4:1)
Trace
9
THF (4:1)
2
10
11
12
13
14
15
16
DME (4:1)
Dioxane (4:1)
DMF (4:1)
MeCN (4:1)
Toluene (4:1)
Dioxane (8:1)
Dioxane (2:1)
1
4
4
4
Trace
2
3
a
19F NMR yield based on PhCF3.
2 mol%.
b

T. Fujita et al. / Journal of Fluorine Chemistry 155 (2013) 97–101
99
Table 2
acids readily participated in the reaction, affording the desired
difluoroethenes 4a–d in high yields.
Monoarylation of 1,1-dibromo-2,2-difluoroethene (1).
Pd2dba3•CHCl3 (0.5 mol%)
dppm (1 mol%)
3. Conclusion
Ar1B(OH)2 (1.0 equiv)
Br
Br
Ar1
Ar1
We synthesized unsymmetrically disubstituted 1,1-diaryl-2,2-
difluoroethenes 4 via stepwise Suzuki–Miyaura coupling reactions,
starting from1,1-dibromo-2,2-difluoroethene(1). The key tosuccess
was using the most appropriate ligand in each coupling step. These
protocols provide a versatile method for synthesizing 1,1-diaryl-2,2-
difluoroethenes, involving the direct coupling of 1,1-dibromo-2,2-
difluoroethene. We expect 1,1-diaryl-2,2-difluoroethenes formed
using this method to be biologically active compounds and
important intermediates for further chemical transformations.
CsF (2.0 equiv)
F
F
F
Br
Ar1
Dioxane–H2O (2:1)
60 °C, 3 h
F
F
F
1
2
3
.
Ar1B (OH)2
2a
Yield (%)a
1
2a, 86%
(3a, 3%)
Br
Br
Br
(HO)2B
F
4. Experimental
F
F
F
4.1. General information
2
3
2b, 69%
(3b, 3%)
(HO)2B
(HO)2B
IR spectra were recorded on a Horiba FT-300S spectrometer.
NMR spectra were recorded on a Bruker Avance 500 spectrometer
in CDCl3 at 500 MHz (1H NMR), at 126 MHz (13C NMR), and at
470 MHz (19F NMR). Chemical shifts were given in ppm relative to
F
F
internal Me4Si (for 1H NMR:
= 77.0), and C6F6 (for 19F NMR:
d
= 0.00), CDCl3 (for 13C NMR:
= 0.0). High resolution mass
2c, 83%
(3c, 4%)
d
d
spectroscopy (HRMS) was conducted with
spectrometer.
a JMS-T100GCV
Ph
OMe
F
1,1-Dibromo-2,2-difluoroethene, purchased from SynQuest
Labs, Inc., was used without further purification. Unless otherwise
noted, materials were obtained from commercial sources and used
directly without further purification. Column chromatography was
performed on silica gel (Kanto, spherical and neutral, 63–210 mesh).
Spectral data for compounds 2a [10,11], 2b [12], 2d [12], and 2e
[11] showed good agreement with the literature data. As for
compounds 2a, 2b, 2d, and 2e, we present only NMR data in this
section.
Ph
4
2d, 59%
(3d, 5%)
(HO)2B
(HO)2B
Br
Br
F
F
F
F
OMe
F
5
2e, 68%
(3e, 5%)
4.2. Synthesis of 1-aryl-1-bromo-2,2-difluoroethenes 2
4.2.1. Typical procedure for the synthesis of 1-aryl-1-bromo-2,2-
difluoroethenes 2
Isolated yield (in parentheses is shown 19F NMR yield based on PhCF3).
a
In a pyrex-glass tube were placed phenylboronic acid (61 mg,
0.50 mmol), CsF (152 mg, 1.0 mmol), Pd2dba3ꢀCHCl3 (2.6 mg,
The synthesis of several unsymmetrically disubstituted 1,1-
2.5
mmol), and dppm (1.9 mg, 4.9 mmol). After the tube was
diaryl-2,2-difluoroethenes 4 was examined under the conditions
described above (Table 4). Both para-substituted (Me, OMe, and F;
Entries 1–3) and ortho-substituted (Me; Entry 4) phenylboronic
purged with nitrogen, a pre-degassed mixed solvent (2.5 mL, 1,4-
dioxane/water = 2:1) and 1,1-dibromo-2,2-difluoroethylene (1,
48
mL, 0.50 mmol) was added to the tube. After stirring for 3 h
at 60 8C, the mixuture was quenched with NH4Cl aq., and organic
materials were extracted with ether three times. The combined
extracts were washed with brine and dried over Na2SO4. After
removal of solvent under reduced pressure, the residue was
purified by column chromatography on silica gel (pentane) to give
2a (95 mg, 86%) as a colorless oil.
Table 3
Effects of the ligand in the second Suzuki–Miyaura coupling.
Pd2dba3•CHCl3 (0.5 mol%)
Ligand 2 (x mol%)
4-FC6H4B(OH)2
CsF (1.0 equiv)
F
Br
(1.0 equiv)
F
4.2.2. Spectra data of 1-aryl-1-bromo-2,2-difluoroethenes 2
F
F
4.2.2.1. 1-Bromo-1-phenyl-2,2-difluoroethene (2a). Colorless oil. 1H
Dioxane–H2O (2:1)
110 °C, 11 h
F
Ph
Ph
4c
NMR(500 MHz, CDCl3):
d
7.33(tt, J = 7.3,1.3 Hz, 1H), 7.39(dd, J = 7.4,
79.9
2c
7.3 Hz, 2H), 7.48–7.51 (m, 2H). 13C NMR (126 MHz, CDCl3):
d
.
(dd, JCF = 35, 26 Hz), 128.5, 128.80, 128.84 (d, JCF = 4 Hz) 131.6 (d,
JCF = 3 Hz), 153.1 (dd, JCF = 295, 287 Hz). 19F NMR (470 MHz, CDCl3):
Entry
Ligand 2
x (mol%)
4c (%)a
d
77.1 (d, JFF = 28 Hz), 83.3 (d, JFF = 28 Hz).
1
2
3
4
PPh3
2
2
1
1
72
50
70
27
AsPh3
dppf
4.2.2.2. 1-Bromo-1-(4-methylphenyl)-2,2-difluoroethene (2b). Col-
orless oil 1H NMR (500 MHz, CDCl3):
2.37 (s, 3H), 7.19 (d,
J = 7.8 Hz, 2H), 7.37 (d, J = 7.8 Hz, 2H). 13C NMR (126 MHz, CDCl3):
dppm
d
a
19F NMR yield based on PhCF3.
d

100
T. Fujita et al. / Journal of Fluorine Chemistry 155 (2013) 97–101
Table 4
4.2.2.4. 1-Bromo-2,2-difluoro-1-(4-methoxyphenyl)ethene
(2d). Colorless oil. 1H NMR (500 MHz, CDCl3):
3.83 (s, 3H), 6.90
(d, J = 9.0 Hz, 2H), 7.41 (d, J = 9.0 Hz, 2H). 13C NMR (126 MHz,
CDCl3): 55.5, 79.6 (dd, JCF = 35, 26 Hz), 113.9, 123.8 (d,
Synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes 4.
d
•
Pd2dba3 CHCl3 (0.5 mol%)
d
PPh3 (2 mol%)
JCF = 3 Hz), 130.2 (dd, JCF = 3, 3 Hz), 152.8 (dd, JCF = 293,
Ar2B(OH)2 (1.1 equiv)
CsF (2.0 equiv)
Br
Ar2
286 Hz), 159.9. 19F NMR (470 MHz, CDCl3):
d
75.7 (d, JFF = 36 Hz),
F
F
81.9 (d, JFF = 36 Hz).
Dioxane–H2O (2:1)
120 °C, 12 h
F
F
4.2.2.5. 1-Bromo-2,2-difluoro-1-(4-fluorophenyl)ethene (2e). Colorless
oil 1H NMR (500 MHz, CDCl3):
7.08 (dd, J = 8.7, 8.7 Hz, 2H), 7.45–
7.49 (m, 2H). 13C NMR (126 MHz, CDCl3):
78.8 (dd, JCF = 35, 27 Hz),
Ph
Ph
d
2c
4
d
.
115.6 (d, JCF = 22 Hz), 127.7 (dd, JCF = 3 Hz), 130.8 (ddd, JCF = 9, 3, 3 Hz),
153.1 (dd, JCF = 294, 287 Hz), 162.7 (d, JCF = 250 Hz). 19F NMR
Entry
1
Ar2B(OH)2
4
Yield (%)
(470 MHz, CDCl3):
d 49.9–50.0 (m), 76.9 (d, JFF = 31 Hz), 83.2 (d,
4a, 93%
(HO)2B
(HO)2B
JFF = 31 Hz).
4.3. Synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes 4
4.3.1. Typical procedure for the synthesis of 1,1-diaryl-2,2-
difluoroethenes 4
F
F
In a pyrex-glass tube were placed 1-bromo-1-(biphenyl-4-yl)-
2,2-difluoroethene (2c, 89 mg, 0.30 mmol), 4-methylphenylboronic
acid (45 mg, 0.33 mmol), CsF (91 mg, 0.60 mmol), Pd2dba3ꢀCHCl3
Ph
Ph
2
4b, 92%
OMe
(1.6 mg, 1.5
mmol), and PPh3 (1.6 mg, 6.1 mmol). After the tube was
purged with nitrogen, a pre-degassed mixed solvent (3.0 mL, 1,4-
dioxane/water = 2:1) was added to the tube. After stirring for 12 h at
120 8C, the mixuture was quenched with NH4Cl aq., and organic
materials were extracted with ether three times. The combined
extracts were washed with brine and dried over Na2SO4. After
removal of solvent under reduced pressure, the residue was purified
by column chromatography on silica gel (hexane/EtOAc = 50:1) to
give 4a (86 mg, 93%) as a white solid.
OMe
F
F
3a
4c, 72%
4.3.2. Spectra data of 1,1-diaryl-2,2-difluoroethenes 4
(HO)2B
(HO)2B
F
4.3.2.1. 1-(Biphenyl-4-yl)-2,2-difluoro-1-(4-methylphenyl)ethene
(4a). White solid. 1H NMR (500 MHz, CDCl3):
d
2.40 (s, 3H), 7.19 (s,
4H), 7.33–7.37 (m, 3H), 7.44 (dd, J = 7.7, 7.7 Hz, 2H), 7.57 (d,
J = 8.4 Hz, 2H), 7.60 (d, J = 7.1 Hz, 2H). 13C NMR (126 MHz, CDCl3):
F
d
F
F
21.4, 96.0 (dd, JCF = 18, 18 Hz), 127.20, 127.20, 127.6, 129.0, 129.3,
129.8 (dd, JCF = 3, 3 Hz), 130.1 (dd, JCF = 3, 3 Hz), 131.4 (dd, JCF = 3,
3 Hz), 133.7 (dd, JCF = 4, 4 Hz), 137.6, 140.4, 140.7, 153.9 (dd,
JCF = 294, 294 Hz). 19F NMR (470 MHz, CDCl3):
F
F
Ph
Ph
d 73.7 (d,
4
4d, 88%
JFF = 33 Hz), 74.1 (d, JFF = 33 Hz). IR (neat):
n
˜ ¼ 2924, 1699, 1242,
982, 820, 766, 692 cmꢁ1. HRMS (EI): m/z calcd. for C21H16F2 ([M]+):
306.1220; Found: 306.1217.
4.3.2.2. 1-(Bipnenyl-4-yl)-2,2-difluoro-1-(4-methoxyphenyl)ethene
(4b). White solid. 1H NMR (500 MHz, CDCl3):
d 3.83 (s, 3H), 6.91 (d,
J = 9.1 Hz, 2H), 7.23 (d, J = 9.1 Hz, 2H), 7.33–7.39 (m, 3H), 7.45 (dd,
J = 7.6, 7.6 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H).
13C NMR (126 MHz, CDCl3):
d 55.4, 95.6 (dd, JCF = 19, 19 Hz), 114.0,
a
4-FC6H4B(OH)2 (1.0 equiv).
126.5 (dd, JCF = 4, 4 Hz), 127.16, 127.16, 127.6, 128.9, 130.0 (dd,
JCF = 3, 3 Hz), 131.0 (dd, JCF = 3, 3 Hz), 133.7 (dd, JCF = 4, 4 Hz), 140.4,
140.7, 153.8 (dd, JCF = 293, 293 Hz), 159.1. 19F NMR (470 MHz,
21.2, 79.9 (dd, JCF = 35, 26 Hz), 128.7 (dd, JCF = 4, 4 Hz), 130.8 (dd,
JCF = 4, 4 Hz), 139.0, 153.0 (dd, JCF = 294, 286 Hz). 19F NMR
CDCl3):
n
˜
d 73.2 (d, JFF = 33 Hz), 73.6 (d, JFF = 33 Hz). IR (neat):
(470 MHz, CDCl3):
d 76.5 (d, JFF = 32 Hz), 82.6 (d, JFF = 32 Hz).
¼ 2960, 1699, 1512, 1246, 1178, 984, 835, 766 cmꢁ1. HRMS (EI):
m/z calcd. for C21H16F2O ([M]+): 322.1169; Found: 322.1169.
4.2.2.3. 1-(Biphenyl-4-yl)-1-bromo-2,2-difluoroethene (2c). White
solid. 1H NMR (500 MHz, CDCl3):
7.30 (tt, J = 7.3, 1.3 Hz, 1H),
7.38 (dd, J = 7.7, 7.7 Hz, 2H), 7.49–7.55 (m, 6H). 13C NMR (126 MHz,
CDCl3): 79.8 (dd, JCF = 34, 26 Hz), 127.1, 127.2, 127.8, 128.9, 129.2
(dd, JCF = 4, 4 Hz), 130.5 (d, JCF = 4 Hz), 140.1, 141.7, 153.2 (dd,
JCF = 295, 287 Hz). 19F NMR (470 MHz, CDCl3):
77.5 (d,
d
4.3.2.3. 1-(Bipnenyl-4-yl)-2,2-difluoro-1-(4-fluorophenyl)ethene
(4c). White solid. 1H NMR (500 MHz, CDCl3):
8.7 Hz, 2H), 7.28, (dd, J = 8.9, 1.0 Hz, 2H), 7.32 (dd, J = 8.5, 1.2 Hz,
2H), 7.36 (tt, J = 7.4, 1.2 Hz, 1H), 7.45 (dd, J = 7.6, 7.6 Hz, 2H), 7.57–
7.61 (m, 4H). 13C NMR (126 MHz, CDCl3):
d 7.07 (dd, J = 8.7,
d
d
d 95.2 (dd, JCF = 19,
JFF = 30 Hz), 83.8 (d, JFF = 30 Hz). IR (neat):
841, 764, 692 cmꢁ1. HRMS (EI): m/z calcd. for C14H979BrF2 ([M]+):
293.9856; Found: 293.9863.
n
˜
¼ 1709, 1290, 984,
19 Hz), 115.5 (d, JCF = 22 Hz), 127.0, 127.1, 127.5, 128.8, 129.8 (dd,
JCF = 3, 3 Hz), 130.1 (dd, JCF = 3, 3 Hz), 131.4 (ddd, JCF = 8, 8, 3 Hz),

T. Fujita et al. / Journal of Fluorine Chemistry 155 (2013) 97–101
101
(a) I.A. McDonald, J.M. Lacoste, P. Bey, M.G. Palfreyman, M. Zreika, J. Med. Chem.
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133.1 (dd, JCF = 3, 3 Hz), 140.4, 140.5, 153.8 (dd, JCF = 294, 294 Hz),
162.1 (d, JCF = 248 Hz). 19F NMR (470 MHz, CDCl3):
74.2 (d, JFF = 32 Hz), 74.3 (d, JFF = 32 Hz). IR (neat):
d
47.7–47.6 (m),
n
˜
¼ 1707, 1508,
1247, 987, 835 cmꢁ1. HRMS (EI): m/z calcd. for C20H13F3 ([M]+):
(d) P.M. Weintraub, A.K. Holland, C.A. Gates, W.R. Moore, R.J. Resvick, P. Bey, N.P.
Peet, Bioorg. Med. Chem. 11 (2003) 427–431;
310.0969; Found: 310.0965.
(e) J.-M. Altenburger, G.Y. Lassalle, M. Matrougui, D. Galtier, J.-C. Jetha, Z. Bocskei,
C.N. Berry, C. Lunven, J. Lorrain, J.-P. Herault, P. Schaeffer, S.E. O’Connor, J.-M.
Herbert, Bioorg. Med. Chem. 12 (2004) 1713–1730;
4.3.2.4. 1-(Bipnenyl-4-yl)-2,2-difluoro-1-(2-methylphenyl)ethene
(4d). White solid. 1H NMR (500 MHz, CDCl3):
d 2.19 (s, 3H), 7.25–
7.29 (m, 6H), 7.34 (t, J = 7.4 Hz, 1H), 7.43 (dd, J = 7.7, 7.7 Hz, 2H),
7.54 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.2 Hz, 2H). 13C NMR (126 MHz,
(f) J. Ichikawa, J. Synth. Org. Chem. Jpn. 68 (2010) 1175–1184.
[5] For synthetic methods for symmetrical 1,1-diaryl-2,2-difluoroethenes, see:
(a) M. Obayashi, E. Ito, K. Matsui, K. Kondo, Tetrahedron Lett. 23 (1982)
2323–2326;
CDCl3): d 19.6, 94.5 (dd, JCF = 23, 15 Hz), 126.1, 127.0, 127.1, 127.4,
(b) R. Ocampo, W.R. Dolbier Jr., R. Paredes, J. Fluorine Chem. 88 (1998) 41–50;
(c) G. Mloston´ , J. Roman´ ski, H. Heimgartner, Heterocycles 50 (1999) 403–410;
(d) I. Nowak, M.J. Robins, Org. Lett. 7 (2005) 721–724;
128.4, 128.5 (dd, JCF = 6, 3 Hz), 128.8, 130.5, 131.0 (dd, JCF = 2, 2 Hz),
132.8 (d, JCF = 4 Hz), 132.9 (d, JCF = 4 Hz), 137.7 (d, JCF = 3 Hz), 139.8,
140.5, 153.4 (dd, JCF = 299, 288 Hz). 19F NMR (470 MHz, CDCl3):
(e) S.Y. Han, H.Y. Lee, J.H. Jeon, I.H. Jeong, Tetrahedron Lett. 53 (2012) 1833–1836.
[6] For synthetic methods for unsymmetrical 1,1-diaryl-2,2-difluoroethenes, see:
(a) A. Raghavanpillai, D.J. Burton, J. Org. Chem. 71 (2006) 194–201;
(b) J.H. Choi, I.H. Jeong, Tetrahedron Lett. 49 (2008) 952–955;
(c) S.Y. Han, I.H. Jeong, Org. Lett. 12 (2010) 5518–5521.
[7] J. Barluenga, P. Moriel, F. Aznar, C. Valde´s, Adv. Synth. Catal. 348 (2006) 347–353.
[8] (a) Y. Takeda, M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 46 (2007) 8659–8661;
(b) D. Alloatti, G. Giannini, W. Cabri, I. Lustrati, M. Marzi, A. Ciacci, G. Gallo, M.O.
Tinti, M. Marcellini, T. Riccioni, M.B. Guglielmi, P. Carminati, C. Pisano, J. Med. Chem.
51 (2008) 2708–2721;
(c) G. Chelucci, Chem. Rev. 112 (2012) 1344–1462 (and references cited therein).
[9] Although synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes had been
reported once by the Suzuki–Miyaura coupling of 1,1-dichloro-2,2-difluor-
oethene using a water-soluble phosphine ligand, the paper was retracted later,
see: J. Pschierer, N. Perschek, H. Plenio, Green Chem. 12 (2010) 636–642. Retrac-
tion was endorsed by Sarah Ruthven, Editor, and published on 15th September
2010.
d
73.1 (d, JFF = 31 Hz), 78.2 (d, JFF = 31 Hz). IR (neat):
n
˜
¼ 1705, 1487,
1244, 984, 841, 764, 696 cmꢁ1. HRMS (EI): m/z calcd. for C21H16F2
([M]+): 306.1220; Found: 306.1207.
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