Synthesis of functionalized fluorinated terphenyls by site-selective Suzuki-Miyaura cross-coupling reactions of dibrominated fluorobenzenes

Article abstract of DOI:10.1016/j.jfluchem.2012.12.003

A variety of fluorinated terphenyls were prepared by site-selective Suzuki-Miyaura cross-coupling reactions of dibrominated fluorobenzenes, such as 1,2-dibromo-3,5-difluorobenzene, 1,4-dibromo-2-fluorobenzene, 1,3-dibromo-4-fluorobenzene, and 1,2-dibromo-4-fluorobenzene.

Full text of DOI:10.1016/j.jfluchem.2012.12.003

Journal of Fluorine Chemistry 146 (2013) 19–36
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of functionalized fluorinated terphenyls by site-selective
Suzuki–Miyaura cross-coupling reactions of dibrominated fluorobenzenes
Muhammad Sharif a,b,c, Aneela Maalik a,b,c, Sebastian Reimann a,b, Holger Feist a, Jamshed Iqbal d,
e
a
a,b,
*
´
Tamas Patonay , Alexander Villinger , Peter Langer
a Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, D-18059 Rostock, Germany
b Leibniz-Institute for Catalysis e.V. at the University of Rostock (LIKAT), Albert-Einstein-Str. 3a, D-18059 Rostock, Germany
c Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, Pakistan
d Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan
e Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Egyetem te´r 1, Hungary
A R T I C L E I N F O
A B S T R A C T
Article history:
A variety of fluorinated terphenyls were prepared by site-selective Suzuki–Miyaura cross-coupling
reactions of dibrominated fluorobenzenes, such as 1,2-dibromo-3,5-difluorobenzene, 1,4-dibromo-2-
fluorobenzene, 1,3-dibromo-4-fluorobenzene, and 1,2-dibromo-4-fluorobenzene.
ß 2012 Elsevier B.V. All rights reserved.
Received 13 August 2012
Received in revised form 9 December 2012
Accepted 10 December 2012
Available online 6 January 2013
Keywords:
Benzene derivatives
Organofluorine compounds
Suzuki–Miyaura reaction
Regioselectivity
Cross-coupling
1. Introduction
of fluorinated arenes are used also for applications in organoca-
talysis [5].
A large number of pharmaceuticals and agrochemicals contain
fluorinated aromatic (Ar–F) groups, which enhance solubility,
bioavailability, and metabolic stability compared with nonfluori-
nated analogs [1]. Fluorinated arenes are important core structures
in medicinal chemistry [1]. The fluorine atom is small, but highly
electronegative and plays an important role in drug–receptor
interactions. Due to the lipophilicity of fluorinated molecules, their
bioavailability is improved. In addition, the C–F bond of arenes is
metabolically more stable as compared to the C–H bond. Several
heterocyclic pharmaceuticals, such as the well known quinolones
ciprofloxacin, ofloxacin, or norfloxacin, contain a fluorinated aryl
group [2]. Aryl fluorides also occur in natural products and their
Aryl fluorides are available by reaction of arenes with strong
electrophilic fluorination agents (such as fluorine or xenon
fluorides) [6]. However, these reagents are difficult to handle
and dangereous, or, in case of xenon fluorides, very expensive.
Selectfluor is an electrophilic fluorination agent which is commer-
cially available and easy to handle [7]. However, the fluorination of
non-activated arenes is, in general, not possible, while activated
substrates, such as anisol or phenol, can result in the formation
of ortho/para mixtures [8]. An alternative approach to the synthesis
of fluorinated arenes relies on electrophilic substitution reactions
of simple fluorinated arenes, such as 4-fluorophenol [9]. However,
these transformations often suffer from low yields, due to the
electron withdrawing effect of the fluorine atom, and may result in
the formation of regioisomeric mixtures. In recent years, palladium
catalyzed cross-coupling reactions, such as the Suzuki–Miyaura
reactions, have been extensively studied [10]. In this context, the
development of site-selective reactions is of special interest [11]. In
palladium catalyzed cross-coupling reactions, the fluoride is a
considerably less reactive leaving group as compared to the
bromide or iodide groups. Our strategy for the synthesis of
substituted fluorinated arenes is based on the idea to develop
palladium catalyzed coupling reactions of bromo-fluoroarenes or
analogues, such as 4-fluoro-zaragozic acid
A or fluorinated
carbazole alkaloids [3]. Organofluorine compounds show a very
good solubility in fluorophilic solvents. Therefore, they are used as
ligands for catalytic reactions in fluorous biphase systems and
supercritical carbon dioxide [4]. The unique electronic properties
* Corresponding author at: University of Rostock, Department of Chemistry,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.12.003

20
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
Table 1
fluoro-iodoarenes. Recently, we have reported site-selective
Suzuki–Miyaura and Sonogashira reactions of 1,2-dibromo-3,5-
difluorobenzene and of 1,4-dibromo-2-fluorobenzene [12]. Both
substrates contain two, rather than only one bromide leaving
group which gives rise to the issue of site-selectivity. Herein, we
report full details of this study and an extension of the scope with
regard to the substrates. In this context, we report, for the first
time, Suzuki–Miyaura reactions of 1,3-dibromo-4-fluorobenzene
and of 1,2-dibromo-4-fluorobenzene.
Synthesis of 3a-i.
2
3
Ar
3(%)a
a
b
c
d
e
h
p
s
a
b
c
d
e
f
C6H5
65
45
60
70
68
58
45
70
48
4-MeC6H4
2-(MeO)C6H4
4-(MeO)C6H4
4-(EtO)C6H4
2,4-(MeO)2C6H3
4-FC6H4
g
h
i
3-(MeO)C6H4
3-MeC6H4
t
2. Results
a
Yields of isolated products.
2.1. 1,2-Dibromo-3,5-difluorobenzene:
The Suzuki–Miyaua reaction of commercially available 1,2-
dibromo-3,5-difluorobenzene (1) with two equivalents of aryl-
boronic acids 2a–e,h,p,s,t afforded difluorinated ortho-terphenyls
3a–i in moderate to good yields (Scheme 1, Table 2). The best yields
were obtained using 2.2 equivalents of the arylboronic acid,
Pd(PPh3)4 (0.03 equiv) as the catalyst, and Cs2CO3 (2.2 equiv) as the
base (1,4-dioxane, 90 8C, 8 h) (Table 1).
The Suzuki–Miyaua reaction of 1 with arylboronic acids 2b-h,p
(1.0 equiv) afforded 2-bromo-3,5-difluoro-biphenyls 4a–h in good
yields and with very good site-selectivity (Scheme 1, Table 2). The
formation of the opposite regioisomer was not observed.
The one-pot reaction of 1,2-dibromo-3,5-difluorobenzene (1)
with two different arylboronic acids afforded the unsymmetrical
difluorinated ortho-terphenyls 5a–g containing two different
terminal aryl groups (Scheme 1, Table 3).
Table 2
Synthesis of 4a-h.
2
4
Ar
4(%)a
b
c
a
b
c
4-MeC6H4
45
60
60
65
60
68
67
63
2-(MeO)C6H4
4-(MeO)C6H4
4-(EtO)C6H4
3,4-(MeO)2C6H3
2,6-(MeO)2C6H3
2,4-(MeO)2C6H3
4-FC6H4
d
e
f
d
e
f
g
h
p
g
h
a
Yields of isolated products.
Table 3
Synthesis of 5a-g.
The structures of all products were established by spectroscopic
methods. The structure of 4g was independently confirmed by X-
ray crystal structure analyses (Fig. 1) [13]. The aryl groups are
twisted out of plane.
The structure of compound 4g has also been confirmed by 2D
NMR (NOESY; HMBC) (Fig. 2). Hydrogen atom H-6 of ring B
2
5
Ar1
Ar2
5(%)a
b,h
d,r
d,a
c,b
g,b
h,b
p,o
a
b
c
d
e
f
4-MeC6H4
2,4-(MeO)2C6H3
56
68
70
62
60
48
45
4-(MeO)C6H4
4-(MeO)C6H4
2-(MeO)C6H4
2,5-(MeO)2C6H3
2,4-(MeO)2C6H3
4-FC6H4
2-MeC6H4
C6H5
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
resonates at
correlation with hydrogen atom H-6 of ring A resonating at
= 6.89 ppm. This proved the bonding of the aryl group at carbon
d = 7.08 ppm and shows a clear and important NOESY
d
g
atom C-1 of ring A. In addition, HMBC correlation of H-6 with
carbon atom C-1 of ring A confirmed that the aryl group is linked to
carbon atom C-1 of ring A.
a
Yields of isolated products.
2.2. 1,4-Dibromo-2-fluorobenzene:
F
Ar
The Suzuki–Miyaua reaction of commercially available 1,4-
dibromo-2-fluorobenzene 6 with 2 equivalents of arylboronic
acids 2b,d-f,h-j,l,n,p,t,u,w,x afforded the fluorinated para-terphe-
nyls 7a–n in moderate to good yields (Scheme 2, Table 4). The best
yields were obtained using 2.2 equivalents of the arylboronic acid,
Pd(PPh3)4 (3 mol%) as the catalyst and Cs2CO3 (2.2 equiv) as the
base (1,4-dioxane, 90 8C, 8 h).
The Suzuki–Miyaua reaction of 6 with arylboronic acids
2b,d,f,i,j,n,o (1.0 equiv) afforded biaryls 8a–h in good yields and
very good site-selectivity (Scheme 2, Table 5). The formation of the
opposite regioisomer was not observed. The chromatographic
purification has a great influence on the yield, due to some losses of
material. In the crude product mixture of 8a–h, before the
chromatographic purification, a small amount of double-coupling
product was present. The structures of all products were confirmed
by spectroscopic methods. The structure of 8f was independently
confirmed by X-ray crystal structure analysis [12b].
ArB(OH)2
2a-e,h,p,s,t
F
Ar
i
3a-i
ArB(OH)2
2b-h,p
F
F
Br
Ar
Br
Br
ii
F
F
4a-h
1
1) Ar1B(OH)2
F
2b-d,g,h,p
2) Ar2B(OH)2
2a-b,h,o,r
Ar2
Ar1
F
iii
5a-g
The one-pot reaction of 1,4-dibromo-2-fluorobenzene 6 with
two different arylboronic acids afforded the unsymmetrical
fluorinated para-terphenyls 9a–f containing two different terminal
aryl groups (Scheme 2, Table 6). Inspection of the NMR of the crude
products 9a–f showed that a small amount of mono- and double-
coupling product were present in most cases.
Scheme 1. Reagents and conditions: i, synthesis of 3a–i: 1 (1.0 equiv), 2 (2.2 equiv),
Cs2CO3 (2.2 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C, 8 h. ii, Synthesis of 4a–h,
1 (1.0 equiv), 2b-h,p (1.0 equiv), Cs2CO3 (1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-
dioxane, 90 8C, 9 h. iii, One-pot synthesis of 5a–g, 1 (1.0 equiv), 2b–d,g,h,p (1.0
equiv), Cs2CO3 (1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C, 8 h, 2a–b,h,o,r
(1.2 equiv), Cs2CO3 (1.5 equiv), 90 8C, 8 h.

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
21
Table 4
Synthesis of 7a–n.
2
7
Ar
7(%)a
b
d
e
f
a
b
c
d
e
f
4-MeC6H4
60
52
65
58
63
45
63
52
48
60
50
60
81
76
4-(MeO)C6H4
4-(EtO)C6H4
3,4-(MeO)2C6H3
2,4-(MeO)2C6H3
4-(Vinyl)C6H4
4-tBuC6H4
h
i
j
g
h
i
l
4-(Acetyl)C6H4
4-FC6H4
p
t
j
3-MeC6H4
u
n
w
x
k
l
2-Thienyl
3-ClC6H4
m
n
4-EtC6H4
2,5-(MeO)2C6H3
Fig. 1. Ortep plot of 4g.
a
Yields of isolated products.
F
F
4
Table 5
Synthesis of 8a–h.
A
6
8(%)a
2
2
8
Ar
6.89
b
d
e
f
a
b
c
4-MeC6H4
60
60
68
67
45
58
57
60
142.8
Br
H
4-(MeO)C6H4
4-(EtO)C6H4
3,4-(MeO)2C6H3
4-(Vinyl)C6H4
4-tBuC6H4
121.02
MeO
H
d
e
f
7.08
i
6
2
j
B
n
o
g
h
3-ClC6H4
4
4-ClC6H4
H
H
a
Yields of isolated products.
6.57
6.59
NOESY
HMBC
OMe
Table 6
Synthesis of 9a-f.
Fig. 2. 2D NMR experiments of 4g.
2
9
Ar1
Ar2
9(%)a
f,u
l,d
a
b
c
d
e
f
3,4-(MeO)2C6H3
4-(Acetyl)C6H4
3,5-(Me)2C6H3
4-MeC6H4
2-Thienyl
53
60
78
48
42
67
4-MeOC6H4
C6H5
m,a
b,d
b,l
Ar
4-MeOC6H4
4-(Acetyl)C6H4
4-MeOC6H4
4-MeC6H4
F
d,c
2-MeOC6H4
ArB(OH)2
a
Yields of isolated products.
2b,d-f,h-j,l,n,p,t,u,w,x
Ar
7a-n
2.3. 1,3-dibromo-4-fluorobenzene:
i
Br
The S–M reaction of commercially available 1,3-dibromo-4-
fluorobenzene 10 with two equivalents of arylboronic acids 2a–
d,q,t,u,v,w,x afforded the fluorinated terphenyls 11a–j in moder-
ate to good yields (Scheme 3, Table 7). The best yields were
obtained using 2.2 equivalents of the arylboronic acid, Pd(PPh3)4
(0.03 equiv) as the catalyst, and Cs2CO3 (2.2 equiv) as the base (1,4-
dioxane, 90 8C, 8 h).
The Suzuki–Miyaura reaction of 10 with arylboronic acids
2b,d,w (1.0 equiv) afforded the 3-bromo-4-fluoro-biphenyls 12a–c
in good yields and with very good site-selectivity (Scheme 3,
Table 8). The formation of the opposite regioisomers was not
observed.
The one-pot reaction of 1,3-dibromo-4-fluorobenzene (10) with
two different arylboronic acids afforded the unsymmetrical
fluorinated para-terphenyl 13a containing two different aryl
groups (Scheme 3, Table 9).
The structures of all products were confirmed by spectroscopic
methods. The site-selectivity of 12c was confirmed by 2D NMR
Br
ArB(OH)2
2b,d-f,i,j,n,o
F
F
ii
Br
6
Ar
8a-h
1) Ar1B(OH)2
Ar2
Ar1
2b,d,f,l,m
F
2) Ar2B(OH)2
2a,c,d,l,u
iii
9a-f
Scheme 2. Reagents and conditions: i, synthesis of 7a–n. 1 (1.0 equiv), 2b,d–f,h–
j,l,n,p,t,u,w,x (2.2 equiv), Cs2CO3 (2.2 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane,
90 8C, 6–8 h. ii, Synthesis of 8a–h: 6 (1.0 equiv), 2b,d–f,i,j,n,o (1.0 equiv), Cs2CO3
(1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C, 6–8 h. iii, One-pot synthesis of
9a–f: 6 (1.0 equiv.), 2b,d,f,l,m (1.0 equiv.), Cs2CO3 (1.5 equiv.), Pd(PPh3)4 (3 mol%),
1,4-dioxane, 90 8C, 8 h, 2a,c,d,l,u (1.2 equiv.), Cs2CO3 (1.5 equiv.), 90 8C, 8 h.
(Fig. 3). Hydrogen atom H-6 of ring B resonating at
showed a clear NOESY correlation with hydrogen atom H-2 of ring
A resonating at = 7.76 ppm. This proved the linkage of the aryl
group located to carbon atom C-1 of ring A. Moreover, hydrogen
d = 7.45 ppm
d

22
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
Table 9
F
Synthesis of 13a.
Ar
2
Ar1
Ar2
13(%)a
ArB(OH)2
q,d
4-(CF3)C6H4
4-(MeO)C6H4
58
2a-d,q,t,u,v,w,x
a
Yields of isolated products.
Ar
11a-g
i
F
F
A
F
ArB(OH)2
Br
Br
Br
2b,d,w
ii
Br
10
H
H
Ar
12a-c
NOESY
1) Ar1B(OH)2
B
F
2q
Ar2
2) Ar2B(OH)2
2d
iii
Fig. 3. 2D NMR experiment (NOESY) of compound 12c.
Ar1
13a
F
F
ArB(OH)2
2a-d,q,i,v
Scheme 3. Reagents and conditions: i, synthesis of 11a–j. 10 (1.0 equiv), 2a–
d,q,t,u,v,w,x (2.2 equiv), Cs2CO3 (2.2 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C,
6–8 h. ii, Synthesis of 12a–c. 10 (1.0 equiv), 2b,d,w (1.0 equiv), Cs2CO3 (1.5 equiv),
Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C, 6–8 h. i, One-pot synthesis of 13a. 1) 10 (1.0
equiv), 2q (1.0 equiv), Cs2CO3 (1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C,
8 h; 2) 2d (1.2 equiv), Cs2CO3 (1. 5 equiv), 90 8C, 8 h.
i
Br
Ar
Br
Ar
14
15a-f
Table 7
Scheme 4. Synthesis of 15a–f. Reagents and conditions: i, 14 (1.0 equiv), 2a–d,q,j
(2.2 equiv), Cs2CO3 (2.2 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 8C, 6–8 h.
Synthesis of 11a–j.
2
11
Ar
11(%)a
a
b
c
a
b
c
d
e
f
C6H5
55
62
60
70
45
57
48
58
57
65
Table 10
4-MeC6H4
Synthesis of 15a–f.
2-(MeO)C6H4
4-(MeO)C6H4
4-CF3C6H4
3-MeC6H4
d
q
t
2
15
Ar
15(%)a
a
b
c
d
q
j
a
b
c
d
e
f
C6H5
55
62
70
60
48
45
4-MeC6H4
u
v
w
x
g
h
i
2-Thienyl
2-(MeO)C6H4
4-(MeO)C6H4
4-(Vinyl)C6H4
2,3-(MeO)2C6H3
2,3-(MeO)2C6H3
4-EtC6H4
j
2,5-(MeO)2C6H3
a
Yields of isolated products.
a
Yields of isolated products.
atom H-2 and H-6 of ring B did not show any NOESY correlation
with ring F.
base (1,4-dioxane, 90 8C, 8 h). All attempts to induce site-selective
transformations proved, under various conditions, to be unsuc-
cessful.
2.4. 1,2-Dibromo-4-fluorobenzene:
3. Discussion and conclusions
The Suzuki–Miyaura reaction of commercially available 1,2-
dibromo-4-fluorobenzene 14 with two equivalents of arylboronic
acids 2a–d,i,v afforded the fluorinated terphenyls 15a–f in
moderate to good yields (Scheme 4, Table 10). The best yields
were obtained using 2.2 equivalents of the arylboronic acid,
Pd(PPh3)4 (0.03 equiv) as the catalyst, and Cs2CO3 (2.2 equiv) as the
The site-selective formation of 4a–h and 5a–g can be explained
by steric and electronic reasons. The first attack of palladium(0)-
catalyzed cross-coupling reactions generally occurs at the more
electron-deficient and sterically less hindered position. Position 1
of 1,2-dibromo-3,5-difluorobenzene (1) is sterically less hindered
because it is located next to a bromine and to a hydrogen atom
while position 2 is located next to a bromine and to a fluorine atom
(Fig. 4). In addition, position 1 (located meta to the fluorine atoms)
is considerably more electron-deficient than position 2 (located
Table 8
Synthesis of 12a–c.
2
12
Ar
12(%)a
ortho and para to the fluorine atoms), due to the
p-donating effect
of the fluorine atom. In fact, the 1H NMR signals of aromatic
protons located ortho or para to a fluorine atom are generally
shifted to higher field compared to the proton located in meta
position.
b
a
b
c
4-MeC6H4
4-(MeO)C6H4
4-EtC6H4
63
70
63
d
w
a
Yields of isolated products.

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
23
0.81 mmol), and 1,4-dioxane (4 mL), 3a was isolated as a colorless
solid (62 mg, 65%). Mp. 70–72 8C. 1H NMR (300 MHz, CDCl3):
Br
F
F
F
Br
Br
Br
d
= 6.87–6.94 (m, 1H, ArH), 6.96–7.00 (m, 1H, ArH), 7.04–7.10 (m,
4H, ArH), 7.16–7.24 (m, 6H, ArH). 13C NMR (62.89 MHz, CDCl3):
= 102.7 (d, J = 27.9 Hz, CH), 112.9 (d, J = 3.1 Hz, CH), 127.2 (2CH),
1
d
F
1
1
127.8 (2CH), 127.9 (2CH), 129.6 (2CH), 131.0 (2CH), 133.4 (C),
139.4 (t, J = 2.1 Hz, C), 144.4 (d, J = 9.18 Hz, C), 160.0 (dd, J = 247.2,
12.3 Hz, CF), 161.3 (dd, J = 248.2, 12.6 Hz, CF). 19F NMR (282.4 MHz,
Br
6
Br
10
1
CDCl3):
d
= ꢀ110.61 (CF), ꢀ111.64 (CF). IR (ATR, cmꢀ1):
Fig. 4. Possible explanation for the site-selectivity of cross-coupling reactions of 1, 6
and 10. The arrow shows the sterically less hindered and electronically more
deficient position at which the reaction takes place first.
˜
V ¼ 3065 ðwÞ, 3027 (w), 2923 (w), 2852 (w), 1617 (m), 1589
(m), 1537 (w), 1498 (w), 1465 (m), 1438 (m), 1413 (m), 1328 (m),
1265 (w), 1204 (w), 1155 (w), 1139 (m), 1101 (m), 1038 (w), 997
(m), 918 (w), 874 (w), 866 (m), 840 (m), 780 (m), 766 (s), 716 (w),
697 (s), 632 (m), 597 (m), 557 (m). MS (EI, 70 eV): m/z (%) = 266
(100) [M]+, 264 (14), 251 (36), 244 (26), 238(10). HRMS (EI) calcd.
for C18H12F2 [M]+: 266.09016; found 266.09082.
Similarly, the site-selective formation of 8a–h and 9a–f can also
be explained by steric and electronic reasons. Position 4 of 1,4-
dibromo-2-fluorobenzene (6) is sterically less hindered because it
is located next to two hydrogen atoms while position 1 is located
next to a fluorine atom (Fig. 4). In addition, position 4 (located meta
to the fluorine atom) is more electron-deficient than position 1
4.4. 1,2-Di(40-methylphenyl)-3,5-difluorobenzene(3b):
(located ortho to the fluorine atoms), due to the
p
-donating effect
Starting with 1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
of the fluorine atom. In fact, the 1H NMR signals of aromatic
protons located ortho to a fluorine atom are generally shifted to
higher field compared to the proton located in meta position.
Furthermore, we have reported site-selective Suzuki–Miyaura
reactions of 1,3-dibromo-4-fluorobenzene (10) which provide a
convenient approach to fluorinated terphenyls and biaryls. The
first attack of palladium(0)-catalyzed cross-coupling reactions
occurs at the more electron-deficient and less hindered position.
The low site-selectivity in case of 1,2-dibromo-4-fluorobenzene
(13) can be explained by the fact that the positions 1 and 2, located
meta and para to the fluorine atom, are sterically and electronically
very similar.
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(110 mg, 0.81 mmol) and 1,4-dioxane (4 mL), 3b was isolated as
a colorless solid (48 mg, 45%). Mp. 68–70 8C. 1H NMR (300 MHz,
CDCl3):
ArH), 7.02–7.06 (m, 4H, ArH), 7.08–7.10 (m, 4H, ArH). 13C NMR
(75 MHz, CDCl3): = 21.1, (CH3), 21.3 (CH3), 102.6 (t, J = 24.8 Hz,
d = 2.38 (s, 3H, CH3) 2.40 (s, 3H, CH3), 6.92–6.96 (m, 2H,
d
CH), 112.9 (d, J = 18.5 Hz, CH), 124.4 (d, J = 12.5 Hz, CH), 128.8
(4CH), 129.8 (4CH), 130.8 (2C), 136.7 (2C), 144.4 (dd, J = 4.5, 4.5 Hz,
C), 159.1 (dd, J = 246.1, 11.8 Hz, CF), 160.1 (dd, J = 247.2, 12.6 Hz,
CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ110.24 (CF), ꢀ111.73 (CF). IR
(ATR, cmꢀ1): V ¼ 3027 ðwÞ, 2973 (w), 2923 (w), 2865 (w), 1905 (w),
1611 (w), 1587 (w), 1514 (w), 1453 (w), 1399 (w), 1335 (w), 1267
(w), 1202 (w), 1141 (w), 1111 (w), 1098 (w), 997 (w), 945 (w), 844
(w), 815 (w), 756 (w), 716 (w), 665 (w), 623 (w), 599 (w), 520 (m).
MS (EI, 70 eV): m/z (%) = 294 (100) [M]+, 293 (13), 280 (18), 275
(12), 265(14). HRMS (EI) calcd. for C20H16F2 [M]+: 294.12146;
found 294.12101.
˜
4. Experimental
4.1. General
All reactions were carried out in oven-dried reaction pressure
tubes under Argon atmosphere. Solvents (THF) were distilled and
purged with argon before use. Triethylamine (Et3N) was purchased
from a commercial source (Acros) and purged with argon before
use. Thin layer chromatography (TLC) was run on Merck precoated
aluminium plates (Si 60 F254). Column chromatography was
performed using Merck Silicagel 60 (0.043–0.06 mm). NMR data
were recorded on a Bruker ARX 300 and Bruker ARX 400
spectrometers. 13C and 1H NMR spectra were referenced to signals
of deutero solvents, respectively. Gas chromatography–mass
analysis was carried out on an Agilent HP-5890 instrument with
an Agilent HP-5973 Mass Selective Detector (EI) and HP-5 capillary
column using helium carrier gas. ESI-HRMS measurements were
performed on an Agilent 1969A TOF mass-spectrometer.
4.5. 1,2-Di(20-methoxyphenyl)-3,5-difluorobenzene (3c):
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2-methoxyphenylboronic acid
(123 mg, 0.81 mmol), and 1,4-dioxane (4 mL), 3c was isolated as a
colorless solid (71 mg, 60%). Mp. 111–113 8C. 1H NMR (300 MHz,
CDCl3):
d = 3.42 (s, 3H, OCH3), 3.55 (s, 3H, OCH3), 6.60 (dd, J = 8.3,
0.7 Hz, 1H, ArH), 6.67–6.88 (m, 6H, ArH), 6.94 (dd, J = 7.5, 1.7 Hz,
1H, ArH), 7.05–7.12 (m, 2H, ArH). 13C NMR (62.89 MHz, CDCl3):
d
= 54.9 (OCH3), 55.2 (OCH3), 102.6 (t, J = 26.5 Hz, CH), 110.2 (CH),
110.3 (CH), 113.2 (dd, J = 21.2, 3.5 Hz, CH), 119.7 (CH), 119.9 (CH),
122.1 (dd, J = 17.1, 3.8 Hz, C), 123.1 (C), 128.6 (t, J = 2.1 Hz, C),
128.90 (CH), 128.92 (CH), 131.0 (CH), 131.7 (CH), 141.9 (t,
J = 4.9 Hz, C), 156.0 (C), 157.0 (C), 160.1 (dd, J = 247.2, 12.8 Hz,
4.2. General procedure for Suzuki reactions (3a–i, 4a–h)
CF), 161.6 (dd, JCF = 247.2, 13.3 Hz, CF). 19F NMR (282.4 MHz,
˜
CDCl3):
d
= ꢀ112.82 (CF), ꢀ118.20 (CF). IR (ATR): V ¼ 3067 ðwÞ,
A solution of 1, Cs2CO3, Pd(PPh3)4, and arylboronic acid 2 in 1,4-
dioxane (4 mL per 0.3 mmol of 1) was stirred at 90 8C for 6 or 8 h.
After cooling to r.t. the organic and the aqueous layer were
separated and the latter was extracted with CH2Cl2. The combined
organic layers were dried (Na2SO4), filtered, and the filtrate was
concentrated in vacuo. The residue was purified by column
chromatography.
2956 (w), 2926 (w), 2835 (w), 1616 (w), 1596 (w), 1503 (w), 1494
(w), 1455 (w), 1421 (w), 1338 (w), 1287 (w), 1247 (m), 1201 (w),
1180 (w), 1120 (w), 1089 (w), 1024 (m), 928 (w), 877 (w), 865 (w),
800 (w), 755 (w), 744 (m), 701 (w), 635 (w), 586 (m), 537 (w) cmꢀ1
.
MS (EI, 70 eV): m/z (%) = 326 (100) [M]+, 295 (12), 251 (21), 238
(10). HRMS (EI) calcd. for C20H16O2F2 [M]+: 326.11129; found
326.11090.
4.3. 1,2-Diphenyl-3,5-difluorobenzene (3a):
4.6. 1,2-Di(4-methoxyphenyl)-3,5-difluorobenzene (3d):
Starting with
1
(100 mg, 0.37 mmol), Cs2CO3 (263 mg,
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), phenylboronic acid (98 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2-methoxyphenylboronic acid

24
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
(123 mg, 0.81 mmol), and 1,4-dioxane (4 mL), 3d was isolated as a
colorless oil (58 mg, 70%). 1H NMR (300 MHz, CDCl3):
= 3.59 (s,
3H, OCH3), 3.71 (s, 3H, OCH3), 6.61–6.95 (m, 10H, ArH). 13C NMR
(62.89 MHz, CDCl3): = 55.0 (OCH3), 55.2 (OCH3), 102.6 (dd,
a colorless solid (49 mg, 45%). Mp. 96–98 8C. 1H NMR (300 MHz,
CDCl3): = 6.79–6.88 (m, 1H, ArH), 6.96–7.09 (m, 1H, ArH), 7.22–
7.45 (m, 8H, ArH). 13C NMR (62.89 MHz, CDCl3):
= 103.9 (d,
J = 3.09 Hz, C), 113.5 (t, J = 3.2 Hz, CH), 115.1 (CH), 115.6 (CH),
115.9 (CH), 128.2 (CH), 128.5 (CH), 128.6 (d, J = 2.7 Hz, CH), 128.9
(CH), 129.0 (CH), 130.5 (CH), 130.7 (C), 133.7 (CH), 136.1 (d,
J = 216.5 Hz, CF), 136.6 (d, J = 255.4 Hz, CF), 138.4 (C), 153.5 (d,
J = 234.7 Hz, CF), 157.6 (d, J = 245.8 Hz, CF). 19F NMR (282.4 MHz,
d
d
d
d
J = 29.3, 2.02 Hz, 2CH), 113.4 (d, J = 2.86 Hz, 2CH), 114.2 (2CH),
125.8 (C), 127.7 (CH), 130.7 (2CH), 131.9 (t, J = 2.91 Hz, CH), 132.0
(CH), 144.0 (dd, J = 9.57, 4.16 Hz, C), 158.7 (d, J = 10.8 Hz, C), 160.3
(dd, JCF = 247.0, 12.9 Hz, CF), 161.6 (dd, JCF = 248.1, 14.5 Hz, CF). 19
F
NMR (282.4 MHz, CDCl3):
d
= ꢀ110.45 (CF), ꢀ111.95 (CF). IR (ATR):
CDCl3):
d
= ꢀ98.84 (CF), ꢀ109.67 (CF), ꢀ111.15 (CF), ꢀ115.15 (CF).
V ¼ 3076 ðwÞ, 3035 (w), 2955 (w), 2933 (w), 2836 (w), 2537 (w),
2047 (w), 1887 (w), 1726 (w), 1607 (s), 1587 (s), 1512 (s), 1461 (s),
1439 (s), 1402 (m), 1335 (w), 1289 (m), 1242 (s), 1204 (m), 1175
(s), 1139 (s), 1098 (s), 1034 (s), 997 (s), 874 (m), 827 (s), 799 (s), 760
(m), 732 (m), 665 (w), 585 (s), 543 (s) cmꢀ1. MS (EI, 70 eV): m/z
(%) = 326 (100) [M]+, 251 (21), 239 (11), 238 (11). HRMS (EI) calcd.
for C20H16O2F2 [M]+: 326.11129; found 326.11130.
IR (ATR, cmꢀ1): V ¼ 3084 ðwÞ, 3050 (w), 2925 (w), 1903 (w), 1619
(w), 1587 (m), 1494 (m), 1474 (m), 1424 (m), 1348 (m), 1279 (w),
1222 (m), 1157 (m), 1113 (m), 1088 (s), 1029 (w), 1001 (s), 943 (w),
847 (m), 811 (s), 723 (m), 701 (m), 626 (m), 605 (s), 545 (m). MS (EI,
70 eV); m/z (%) = 302 (100) [M]+, 282 (18). HRMS (EI) calcd. for
˜
˜
C
18H10OF4 [M]+: 302.07131; found 302.07065.
4.10. 1,2-Di(3-methoxyphenyl)-3,5-difluorobenzene (3h):
Starting with (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
4.7. 1,2-Di(40-ethoxyphenyl)-3,5-difluorobenzene(3e):
1
Starting with
1
(100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 3-methoxyphenylboronic acid
(123 mg, 0.81 mmol), and 1,4-dioxane (4 mL), 3h was isolated as
a colorless solid (58 mg, 70%). Mp 118–120 8C.1H NMR (300 MHz,
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid
(135 mg, 0.81 mmol), and 1,4-dioxane (4 mL) 3e was isolated as
a colorless solid (88 mg, 68%). Mp 69–71 8C. 1H NMR (300 MHz,
CDCl3):
1H, ArH), 6.66–6.97 (m, 7H, ArH), 7.06–713 (m, 2H, ArH). 13C NMR
(62.89 MHz, CDCl3): = 55.4 (OCH3), 55.9 (OCH3), 102.6 (t,
d = 3.43 (s, 3H, OCH3), 3.57 (s, 3H, OCH3), 6.61 (d, J = 7.69 Hz,
CDCl3):
d
= 1.36–1.43 (m, 4H, CH2), 3.94–4.03 (m, 6H, OCH3), 6.69–
= 14.8 (CH3),
7.01 (m, 10H, ArH). 13C NMR (62.89 MHz, CDCl3):
d
d
14.9 (CH3), 63.2 (OCH2), 63.3 (OCH2), 102.3 (t, J = 26.5 Hz, CH), 112
(dd, J = 21.8, 3.6 Hz, CH), 113.9 (2CH), 114.0 (2CH), 114.7 (2CH),
125.6 (C), 127.7 (C), 130.7 (2CH), 131.0 (C), 132.2 (C), 157.9 (C),
158.1 (C), 160.0 (dd, JCF = 249.2, 12.6 Hz, CF), 161.1 (dd, JCF = 249.2,
J = 26.4 Hz, C), 110.4 (CH), 113.1 (d, J = 3.6 Hz, CH), 119.2 (d,
J = 16.5 Hz, CH) 123.1 (C), 128.6 (t, J = 2.9 Hz, CH), 130.0 (C), 131.0
(2CH), 156.0 (C), 157.0 (C), 159.0 (dd, JCF = 247.4, 14.31 Hz, CF), 161.7
(dd, JCF = 247.4, 14.31 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
13.3 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ110.09 (CF),
d
= ꢀ110.45 (CF), ꢀ111.95 (CF). IR (ATR): V ¼ 3055 ðwÞ, 2922 (w),
˜
ꢀ112.02 (CF). IR (ATR, cmꢀ1): V ¼ 3062 ðwÞ, 3036 (w), 2975 (w),
2929 (w), 2873 (w), 1730 (w), 1605 (m), 1586 (m), 1511 (m), 1460
(m), 1432 (m), 1393 (m), 1335 (w), 1285 (m), 1239 (s), 1177 (m),
1110 (m), 1046 (m), 997 (m), 934 (w), 867 (m), 819 (s), 758 (m),
647 (w), 616 (m), 594 (w), 559 (m), 536 (m). MS (EI, 70 eV): m/z
(%) = 354 (100) [M]+, 326 (21), 298 (30), 297 (22), 251 (24). HRMS
(EI) calcd. for C22H20O2F2 [M]+: 354.14259; found 354.14230.
2851 (w), 1726 (w), 1618 (w), 1590 (w), 1580 (w), 1494 (w), 1436
(m), 1377 (w), 1336 (w), 1277 (w), 1245 (w), 1177 (m), 1117 (s),
1091 (m), 1026 (m), 996 (m), 877 (w), 838 (w), 798 (w), 747 (s), 720
(s), 692 (s), 637 (m), 587 (w), 538 (s) cmꢀ1. MS (EI, 70 eV); m/z
(%) = 326 (100) [M]+, 295 (13), 251 (22), 238 (11). HRMS (EI) calcd.
for C20H16O2F2 [M]+: 326.11129; found 326.11099.
˜
4.11. 1,2-Di(3-methylphenyl)-3,5-difluorobenzene (3i):
4.8. 1,2-Di(20,40-dimethoxyphenyl)-3,5-difluorobenzene (3f):
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
Starting with
1
(100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 3-methylphenylboronic acid
(110 mg, 0.81 mmol) and 1,4-dioxane (4 mL), 3i was isolated as
a colorless solid (51 mg, 48%). Mp 73–75 8C. 1H NMR (300 MHz,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2,4-dimethoxyphenylboronic
acid (148 mg, 0.81 mmol), and 1,4-dioxane (4 mL), 3f was isolated
as a colorless solid (81 mg, 58%). Mp 96–98 8C. 1H NMR (300 MHz,
CDCl3): d = 3.44 (s, 3H, OCH3), 3.56 (s, 3H, OCH3), 3.68 (s, 3H, OCH3),
3.69 (s, 3H, OCH3), 6.20–6.30 (m, 3H, ArH), 6.72–6.85 (m, 3H, ArH),
7.29–7.42 (m, 1H, ArH), 761–766 (m, 1H, ArH). 13C NMR
CDCl3):
ArH), 7.02–7.06 (m, 4H, ArH), 7.08–7.10 (m, 4H, ArH). 13C NMR
(75 MHz, CDCl3): = 21.1, 21.3 (ArCH3), 102.6 (t, J = 24.8 Hz, CH),
d = 2.38 (s, 3H, CH3) 2.40 (s, 3H, CH3), 6.92–6.96 (m, 2H,
d
112.9 (d, J = 18.5 Hz, CH), 124.4 (d, J = 12.5 Hz, C), 128.8 (4CH),
129.8 (4CH), 130.8 (2C), 136.7 (2C), 144.4 (dd, J = 4.5, 4.5 Hz, C),
159.1 (dd, 1JCF = 246.1, 11.8 Hz, CF), 160.1 (dd, 1JCF = 247.2, 12.6 Hz,
(62.89 MHz, CDCl3):
d = 55.0 (OCH3), 55.2 (OCH3), 55.3 (OCH3),
55.4 (OCH3), 98.1 (d, J = 12.7 Hz, CH), 98.9 (C), 102.4 (d,
J = 109.9 Hz, C), 103.8 (d, J = 16.3 Hz, CH), 113.2 (d, J = 14.5 Hz,
C), 113.8 (d, J = 16.5 Hz, CH), 115.8 (C), 121.2 (t, J = 9.25 Hz, C),
127.9 (t, J = 21.7 Hz, H), 130.2 (C), 131.4 (CH), 131.9 (C), 134.7 (t,
J = 25.5 Hz, CH), 157.5 (d, J = 245.5 Hz, CF), 160.0 (C), 160.3 (C). 19
NMR (282.4 MHz, CDCl3):
CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ110.69 (CF), ꢀ112.19 (CF). IR
(ATR, cmꢀ1): V ¼ 3087 ðwÞ, 3052 (w), 2974 (w), 2923 (w), 2865 (w),
1905 (w), 1610 (w), 1587 (m), 1514 (w), 1453 (w), 1398 (w), 1335
(m), 1310 (w), 1277 (w), 1201 (w), 1141 (m), 1111 (w), 1097 (m),
997 (m), 968 (w), 870 (m), 844 (m), 815 (s), 756 (w), 726 (m), 664
(w), 623 (m), 598 (w), 530 (w). MS (EI, 70 eV): m/z (%) = 294 (100)
[M]+, 293 (12), 280 (18), 279 (87), 278 (22), 277 (11), 265 (14), 264
(45), 259 (10), 257 (10). HRMS (EI) calcd. for C20H16F2 [M]+:
294.12146; found 294.12175.
˜
F
d
= ꢀ110.09 (CF), ꢀ113.03 (CF). IR (ATR,
cmꢀ1): V ¼ 3054 ðwÞ, 2997 (w), 2921 (w), 2851 (w), 1607 (w), 1579
(w), 1508 (w), 1461 (w), 1435 (w), 1410 (w), 1337 (w), 1280 (w),
1205 (m), 1156 (m), 1124 (w), 1092 (m), 1030 (m), 981 (w), 935
(w), 830 (w), 647 (w), 723 (w), 692 (w), 613 (w), 588 (w), 540 (w).
MS (EI, 70 eV): m/z (%) = 386 (100) [M]+, 355 (11). HRMS (EI) calcd.
for C22H20O4F2 [M]+: 386.13242; found 386.13250.
˜
4.12. 2-Bromo-3,5-difluoro-40-methylbiphenyl (4a):
4.9. 1,2-Di(40-fluorophenyl)-3,5-difluorobenzene(3g):
Starting with 1 (100 mg, 0.37 mmol), Cs2CO3 (119 mg,
0.37 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(50 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4a was isolated as
a colorless solid (46 mg, 45%). Mp 68–70 8C. 1HNMR (300 MHz,
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-fluorophenylboronic acid
(114 mg, 0.81 mmol), and 1,4-dioxane (4 mL), 3g was isolated as
CDCl3): d
= 6.85–6.92 (m, 2H, Ar), 7.23–67.29 (m, 4H, Ar). 13C NMR

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
25
(75.46 MHz, CDCl3):
d
= 21.3 (CH3), 103.5 (t, J = 26.6 Hz, CH), 104.9
13C NMR (62.89 MHz, CDCl3):
d
= 14.8 (CH3), 63.5 (OCH2), 103.2 (t,
(dd, J = 20.1, 4.3 Hz, CH), 113.8 (dd, J = 22.6, 3.7 Hz, C), 128.9 (CH),
129.0 (CH), 136.3 (t, J = 2.8 Hz, C), 138.4 (C), 159.6 (dd, JCF = 248.1,
13.2 Hz, CF), 159.9 (CH), 161.6 (dd, JCF = 249.4, 13.6 Hz, CF). 19F
J = 27.0 Hz, CH), 113.5 (d, J = 4.0 Hz, CH), 113.7 (dd, J = 22.2, 3.4 Hz,
C), 114.1 (2CH), 128.4 (d, J = 6.9 Hz, CH), 128.7 (CH), 130.4 (CH),
133.7 (CH), 141.3 (d, J = 9.4 Hz, C), 159.0 (C), 159.3 (dd, JCF = 247.9,
13.3 Hz, CF), 161.3 (dd, JCF = 249.5, 13.3 Hz, CF). 19F NMR
NMR (282.4 MHz, CDCl3):
d
= ꢀ98.94 (CF), ꢀ111.30 (CF). IR (ATR):
˜
V ¼ 3086 ðwÞ, 3028 (w), 2989 (w), 2921 (w), 2856 (w), 1914 (w),
1747 (w), 1666 (w), 1604 (w), 1584 (m), 1514 (m), 1468 (w), 1421
(m), 1398 (m), 1350 (m), 1278 (w), 1205 (w), 1183 (w), 1139 (m),
1111 (m), 1042 (w), 998 (m), 949 (w), 870 (m), 818 (s), 782 (m),
710 (m), 641 (w), 606 (m), 597 (m), 579 (m). MS (EI, 70 eV): m/z
(%) = 284 (97) [M]+ (81Br), 283 (22), 282 (100) (79Br), 201 (67), 183
(53). HRMS (EI) calcd. for C13H9 79BrF2 [M]+: 281.98502; found
281.17032.
(282.4 MHz, CDCl3):
d
= ꢀ101.8 (CF), ꢀ112.5 (CF). IR (ATR):
˜
V ¼ 3067 ðwÞ, 2956 (w), 2926 (w), 2835 (w), 1616 (w), 1596
(w), 1503 (w), 1494 (w), 1455 (w), 1421 (w), 1338 (w), 1287 (w),
1247 (m), 1201 (w), 1180 (w), 1120 (w), 1089 (w), 1024 (m), 928
(w), 877 (w), 865 (w), 800 (w), 755 (w), 744 (m), 701 (w), 635 (w),
586 (m), 537 (w) cmꢀ1. MS (EI, 70 eV): m/z (%) = 312 (61) (79Br)
[M]+, 287 (12), 286 (98), 284 (100), 204(10). HRMS (EI) calcd. for
C
14H11O81BrF2 [M]+: 313.99354; found 313.99349.
4.16. 2-Bromo-3,5-difluoro-30,40-dimethoxybiphenyl (4e):
Starting with (100 mg, 0.37 mmol), Cs2CO3 (119 mg,
4.13. 2-Bromo-3,5-difluoro-20-methoxybiphenyl (4b):
Starting with
1
(100 mg, 0.37 mmol), Cs2CO3 (119 mg,
1
0.37 mmol), Pd(PPh3)4 (3 mol%), 2-methoxyphenylboronic acid
0.37 mmol), Pd(PPh3)4 (3 mol%), 3,4-dimethoxyphenylboronic
(56 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4b was isolated as a
acid (67 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4e was isolated
colorless oil (65 mg, 60%). 1H NMR (300 MHz, CDCl3):
d
= 3.68 (s,
as
(300 MHz, CDCl3):
6.78–6.88 (m, 5H, ArH). 13C NMR (75.46 MHz, CDCl3):
a
colorless solid (72 mg, 60%). Mp 110–112 8C. 1HNMR
3H, OCH3), 6.75–6.81 (m, 1H, ArH), 6.86–6.95 (m, 2H, ArH), 7.03
d
= 3.84 (s, 3H, OCH3), 3.87 (s, 3H, OCH3),
= 55.9
(dd, J = 7.45, 2.00 Hz, 1H, ArH), 7.27–74 (m, 1H, ArH), 7.55–7.62 (m,
d
1H, ArH). 13C NMR (62.89 MHz, CDCl3):
d
= 55.6 (OCH3), 103.6 (t,
(OCH3), 56.0 (OCH3), 103.4 (t, J = 27.2 Hz, CH), 110.7 (CH), 112.5
(CH), 113.8 (dd, J = 22.7, 3.41 Hz, CH), 121.7 (CH), 131.1 (C), 148.4
(C), 149.1 (C), 158.2 (C), 158.4 (C), 159.22 (dd, J = 248.0, 13.7 Hz,
CF), 161.3 (dd, J = 248.6, 13.2 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
J = 27.4 Hz, CH), 106.5 (q, J = 20.7 Hz, CH), 111.0 (C), 114.2 (dd,
J = 3.71 Hz, C), 120.5 (CH), 128.5 (CH), 130.3 (d, J = 26.2 Hz, C),
132.2 (CH), 156.4 (C), 159.2 (dd, JCF = 247.6, 13.4 Hz, CF), 161.3 (dd,
JCF = 248.3, 12.7 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ100.33
d
= ꢀ98.7 (CF), ꢀ111.6 (CF). IR (ATR): V ¼ 3062 ðwÞ, 3016 (w), 2961
˜
˜
(CF), ꢀ111.80 (CF). IR (ATR): V ¼ 3090 ðwÞ, 3056 (w), 3016 (w),
2936 (w), 2835 (w), 1614 (m), 1580 (m), 1495 (m), 1434 (s), 1345
(m), 1296 (m), 1241 (s), 1196 (m), 1119 (s), 1071 (w), 1022 (s), 996
(s), 939 (w), 873 (s), 844 (s), 779 (w), 751 (s), 719 (s), 692 (s), 639
(m), 596 (s), 538 (s) cmꢀ1. MS (EI, 70 eV): m/z (%) = 300 (37) [M]+,
(w), 2848 (w), 1607 (w), 1579 (w), 1518 (w), 1468 (w), 1437 (w),
1398 (w), 1323 (w), 1283 (w), 1235 (w), 1188 (w), 1137 (w), 1108
(w), 1044 (w), 999 (w), 911 (w), 865 (w), 828 (w), 790 (w), 730 (w),
666 (w), 628 (w), 597 (w), 556 (w). MS (EI, 70 eV): m/z (%) = 330
81Br) (97) [M]+, 329 (15), 328 (79Br) (100), 287 (16), 206 (62), 191
(12), 188 (19). HRMS (EI) calcd. for C14H11O281BrF2 [M]+:
329.98845; found 329.98873.
(
(
81Br), 298 (79Br) (37), 219 (33), 205 (12), 204 (100), 188 (14), 175
(21). HRMS (EI) calcd. for C13H9O79BrF2 [M]+: 297.97994; found
297.980349, C13H9O81BrF2 [M]+: 299.97789; found 299.97843.
4.17. 2-Bromo-3,5-difluoro-20,60-dimethoxybiphenyl (4f):
4.14. 2-Bromo-3,5-difluoro-40-methoxybiphenyl (4c):
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
Starting with
1
(100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2,6-dimethoxyphenylboronic
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(56 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4c was isolated as a
colorless solid (65 mg, 60%). Mp 61–62 8C. 1H NMR (300 MHz,
acid (67 mg, 0.37 mmol) and 1,4-dioxane (4 mL), 4f was isolated
as
(300 MHz, CDCl3):
CH), 6.81–6.89 (m, 2H, CH), 7.41 (t, J = 9.0, 1H, ArH). 13C NMR
(75 MHz, CDCl3): = 55.9 (2OCH3), 103.0 (C), 103.4 (t, J = 26.6 Hz,
a
colorless solid (82 mg, 68%). Mp 121–123 8C.1H NMR
d
= 3.76 (s, 6H, OCH3), 6.66 (d, J = 8.4 Hz, 2H,
CDCl3):
d
= 3.86 (s, 3H, OCH3), 6.84–6.98 (m, 4H, ArH), 7.30–7.35
= 55.3 (OCH3), 103.6
(m, 2H, ArH). 13C NMR (62.89 MHz, CDCl3):
d
d
(t, J = 26.8 Hz, CH), 113.6 (2CH), 113.9 (d, J = 3.58 Hz, CH), 114.4 (C),
115.1 (C), 130.4 (2CH), 131.5 (t, J = 2.2 Hz, C), 145.3 (d, J = 8.3 Hz, C)
159.6 (C), 160.0 (dd, JCF = 238.0, 13.4 Hz, CF), 161.4 (dd, JCF = 248.3,
CH), 103.9 (2CH), 114.0 (C), 114.8 (d, J = 4.5 Hz, CH), 130.1 (CH),
138.2 (C), 157.2 (2C), 157.4 (dd, JCF = 247.0 Hz, 12.9 Hz, CF), 160.3
(dd, JCF = 247.6 Hz, 12.1 Hz, CF). 19F NMR (282 MHz, CDCl3):
12.7 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ98.86 (CF),
d
= ꢀ101.15 (CF), ꢀ112.73 (CF). IR (ATR, cmꢀ1): V ¼ 3086 ðwÞ,
˜
˜
ꢀ111.35 (CF). IR (ATR): V ¼ 3094 ðwÞ, 3013 (w), 2964 (w), 2914
(w), 2836 (w), 1889 (w), 1604 (s), 1588 (s), 1514 (s), 1496 (m), 1445
(m), 1377 (m), 1292 (m), 1244 (s), 1205 (m), 1183 (s), 1140 (m),
1071 (w), 1029 (m), 998 (s), 937 (w), 870 (s), 833 (s), 799 (m), 753
(m), 708 (w), 679 (m), 641 (m), 600 (s), 569 (s) cmꢀ1. MS (EI, 70 eV):
m/z (%) = 300 (100) [M]+(81Br), 299 (14), 298 (98) (79Br), 285 (12),
283 (12), 257 (18), 255 (18), 188 (11), 176 (32), 175 (39). HRMS (EI)
calcd. for C13H9O79BrF2 [M]+: 297.97994; found 297.979859
3017 (w), 2959 (m), 2838 (w), 1590(s), 1472 (s), 1416 (m), 1110 (s),
867 (s), 778 (s), 724 (s), 599 (s). GC–MS (EI, 70 eV): m/z (%) = 328
[M]+, (37), 249 (11), 234 (100), 219 (16), 191 (16), 175 (12), 163 (6).
ESI-HRM S calcd. for C14H12BrF2O2 [M + H]+: 328.9983; found
328.9983.
4.18. 2-Bromo-3,5-difluoro-20,40-dimethoxybiphenyl (4g):
C
13H9O81BrF2 [M]+: 299.97789; found 299.97780.
4.15. 2-Bromo-3,5-difluoro-40-ethoxybiphenyl (4d):
Starting with (100 mg, 0.37 mmol), Cs2CO3 (119 mg,
Starting with 1 (100 mg, 0.37 mmol), Cs2CO3 (119 mg,
0.37 mmol), Pd(PPh3)4 (3 mol%), 2,4-dimethoxyphenylboronic
acid (67 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4g was isolated
as a colorless solid (81 mg, 67%). Mp. 64–66 8C. 1H NMR (300 MHz,
1
CDCl3):
Ar), 6.82–6.88 (m, 2H, Ar), 7.04 (d, J = 8.9 Hz, 1H, Ar). 13C NMR
(75.46 MHz, CDCl3): = 55.4 (OCH3), 55.6 (OCH3), 98.7 (CH), 103.4
d = 3.75 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 6.53–6.57 (m, 2H,
0.37 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid
(61 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4d was isolated as
a colorless solid (74 mg, 65%). Mp 111–113 8C. 1H NMR (300 MHz,
d
(t, J = 26.6 Hz, CH), 104 (CH), 106.9 (dd, J = 20.4, 4.0 Hz, C), 114.5
(dd, J = 22.3, 3.3 Hz, CH), 121.0 (t, J = 2.2, C), 131.1 (CH), 142.9 (d,
J = 9.8 Hz, C), 157.4 (C), 159.22 (dd, JCF = 248.0, 13.7 Hz, CF), 161.3
CDCl3):
d = 1.44 (t, J = 6.95 Hz, 3H, CH3), 4.07 (q, J = 6.95, 3H, OCH3),
3.55 (s, 3H, OCH3), 6.83–6.97 (m, 3H, ArH), 7.28–7.34 (m, 3H, ArH).

26
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
(dd, JCF = 248.6, 13.2 Hz, CF), 161.4 (C). 19F NMR (282.4 MHz,
V ¼ 3080 ðwÞ, 2998 (w), 2956 (w), 2836 (w), 1736 (w), 1609 (s),
1586 (s), 1508 (s), 1454 (s), 1425 (m), 1401 (m), 1372 (w), 1303
(s), 1255 (m), 1184 (w), 1158 (s), 1145 (s), 1092 (s), 1032 (s), 996
(s), 925 (m), 861 (w), 834 (m), 818 (s), 796 (m), 736 (w), 718 (w),
663 (w), 607 (w), 587 (m) cmꢀ1. MS (EI, 70 eV): m/z (%) = 340
(100) [M]+, 294 (11), 265 (13), 238 (12). ESI-HRM S calcd. for
C21H19F2O2 [M + H]+: 341.1348; found 341.1348.
˜
˜
CDCl3):
d
= ꢀ100.5 (CF), ꢀ112.4 (CF). IR (ATR): V ¼ 3079 ðwÞ, 3002
(w), 2958 (w), 2937 (w), 2836 (w), 1692 (s), 1785 (s), 1509 (s), 1463
(m), 1447 (m), 1468 (w), 1435 (s), 1345 (w), 1304 (s), 1281 (m),
1256 (m), 1206 (s), 1146 (m), 1127 (s), 1101 (s), 1031 (s), 997 (s),
924 (m), 833 (s), 796 (m), 716 (w), 637 (w), 599 (s), 587 (m) cmꢀ1
MS (EI, 70 eV): m/z (%) = 330 (81Br) (95) [M]+, 328 (81Br) (93), 329
(15), 331 (14), 235 (15), 234 (100), 219 (35), 204 (12), 191 (20), 175
(26), 163 (13). ESI-HRMS calcd. for C14H1279BrF2O2 [M + H]+:
328.9983; found 328.9979.
.
5.2. 1-(40-Methoxyphenyl)-2-(200-methylphenyl)-3,5-
difluorobenzene (5b):
4.19. 2-Bromo-3,5-difluoro-4-fluorobiphenyl (4h):
Starting with 1 (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
1.11 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(112 mg, 0.74 mmol), 1,4-dioxane (4 mL), and 2-methylphenyl-
boronic acid (121 mg, 0.89 mmol), 5b was isolated as a colorless oil
d = 2.14 (s, 3H, CH3),
3.32 (s, 3H, OCH3), 6.72–6.88 (m, 6H, ArH), 6.93–6.97 (m, 1H, ArH),
7.06–7.23 (m, 2H, ArH), 7.23–7.37 (m, 1H, ArH). 13C NMR
Starting with
1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-fluorophenylboronic acid
(52 mg, 0.37 mmol) and 1,4-dioxane (4 mL), 4h was isolated as
a colorless solid (66 mg, 63%). Mp 146–148 8C. 1H NMR (300 MHz,
(155 mg, 68%). 1H NMR (300 MHz, CDCl3):
CDCl3):
d
= 6.74–6.80 (m, 2H, CH), 6.96–7.12 (m, 2H, CH), 7.20–7.26
= 103.8 (t, J = 27.0 Hz, CH),
(m, 2H, CH). 13C NMR (75 MHz, CDCl3):
d
(62.89 MHz, CDCl3): d = 21.2 (CH3), 55.0 (OCH3), 102.8 (CH),
104.9 (d, J = 25.0 Hz, CBr), 103.4 (CH), 113.6 (dd, J = 19.5 Hz, J = 3.0,
110.7 (t, J = 26.3 Hz, CH), 115.0 (CH), 120.3 (CH), 128.0 (CH),
128.1 (CH), 129.2 (CH), 130.10 (CH), 131.2 (C), 133.6 (C), 156.0 (C),
157.7 (C), 159.2 (C), 159.6 (d, J = 13.8 Hz, C), 159.9 (dd, JCF = 248.0,
13.0 Hz, CF), 161.1 (dd, JCF = 247.0, 13.4 Hz, C). 19F NMR
CH), 115.2 (CH), 130.9 (CH), 131.04 (CH), 135.1 (C), 144.6 (C), 157.9
1
3
1
(dd, JCF = 248.0 Hz, JCF = 12.9 Hz, CF), 161.3 (dd, JCF = 248.6 Hz,
3JCF = 12.8 Hz, CF), 161.1 (d, JCF = 245.0 Hz, CF). 19F NMR
1
(282 MHz, CDCl3):
d
= ꢀ98.53 (CF), ꢀ110.91 (CF), ꢀ112.80 (CF).
(282.4 MHz, CDCl3):
d
= ꢀ111.86 (CF), ꢀ112.9 (CF). IR (ATR):
IR (ATR, cmꢀ1): V ¼ 3340 ðwÞ, 2921 (w), 2852 (w), 1904 (w), 1711
(w), 1470 (w), 1455 (w), 1388 (w), 1087 (s), 1002 (s), 811 (s), 701
(m), 625 (w), 544 (m). GC–MS (EI, 70 eV): m/z (%) = 286 (100) (81Br)
[M]+, 207 (23), 206 (77), 188 (11), 187 (20), 186 (13), 103 (11), 93
(5). HRMS (EI, 70 eV) calcd. for C12H6BrF3 [M]+: 285.95995; found
285.959530 and calcd. for C12H681BrF3[M]+: 287.95790; found
287.95753.
V ¼ 3082 ðwÞ, 3053 (w), 3008 (w), 2978 (w), 2928 (w), 2835 (w),
1600 (m), 1558 (w), 1495 (m), 1445 (m), 1394 (m), 1333 (m), 1283
(m), 1241 (s), 1201 (m), 1159 (m), 1091 (m), 1025 (m), 995 (m), 937
(m), 893 (w), 837 (m), 803 (m), 782 (m), 742 (m), 700 (m), 640 (m),
573 (m), 541 (m), 530 (m). MS (EI, 70 eV): m/z (%) = 310 (100) [M]+,
295 (24), 279 (29), 264 (27), 262 (10). HRMS (EI) calcd. for
˜
˜
C
20H16OF2 [M]+: 310.11637; found 310.11557.
5.3. 1-(40-Methoxyphenyl)-2-phenyl-3,5-difluorobenzene (5c):
Starting with (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
5. General procedure for the synthesis of 5a–g
The reaction was carried out in a pressure tube. To a dioxane
suspension (4 mL) of 1 (200 mg, 0.74 mmol), Pd(PPh3)4 (3 mol%),
and Ar1B(OH)2 (0.74 mmol) was added Cs2CO3 (359 mg,
1.11 mmol), and the resultant solution was degassed by bubbling
argon through the solution for 10 min. The mixture was heated at
90 8C under Argon atmosphere for 8 h. The mixture was cooled to
20 8C and Ar2B(OH)2 (0.89 mmol) and Cs2CO3 (359 mg, 1.11 mmol)
was added. The reaction mixtures were heated under Argon
atmosphere for 6 h at 100 8C. They were diluted with H2O and
extracted with CH2Cl2 (3 ꢁ 50 mL). The combined organic layers
were dried (Na2SO4), filtered, and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatography (silica
gel, EtOAc: hexane = 1:4).
1
1.11 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(112 mg, 0.74 mmol), 1,4-dioxane (4 mL), and phenylboronic acid
(107 mg, 0.89 mmol), 5c was isolated as a colorless oil (152 mg,
70%). 1H NMR (300 MHz, CDCl3):
J = 9.13 Hz, 2H, ArH), 6.76–6.83 (m, 1H, ArH), 6.88–6.94 (m, 3H,
ArH), 6.97–7.04 (m, 2H, ArH), 7.11–7.18 (m, 3H, ArH). 13C NMR
d = 3.68 (s, 3H, OCH3), 6.64 (dt,
(62.89 MHz, CDCl3):
d = 55.2 (OCH3), 102.4 (d, J = 27.5 Hz, CH),
112.7 (d, J = 3.72 Hz, C), 112.9 (d, J = 3.72 Hz, C), 113.4 (CH), 124.2
(d, J = 3.50 Hz, C), 124.4 (d, J = 3.50 Hz, CH), 125.6 (C), 127.2 (CH),
129.6 (CH), 130.7 (CH), 130.9 (CH), 131.7 (t, J = 2.74 Hz, C), 132.0
(C), 133.7 (C), 144.0 (d, J = 4.73 Hz, C), 144.1 (d, J = 4.73 Hz, C), 158.8
(C), 160.1 (dd, JCF = 247.2, 12.6 Hz, CF), 161.6 (dd, JCF = 248.4,
13.4 Hz, C). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ110.40 (CF),
5.1. 1-(40-Methylphenyl)-2-(200,400-dimethoyphenyl)-3,5-
ꢀ111.44 (CF). IR (ATR): V ¼ 3061 ðwÞ, 3032 (w), 3000 (w), 2956
(w), 2929 (w), 2836 (w), 2541 (w), 1885 (w),1725 (w), 1608 (s),
1588 (s), 1514 (s), 1461 (m), 1405 (m), 1335 (m), 1291 (m), 1245
(s), 1204 (m), 1176 (s), 1139 (s), 1100 (s), 1072 (m), 1034 (m), 998
(s), 915 (w), 873 (m), 829 (s), 773 (s), 746 (m), 711 (m), 698 (s), 647
(w), 610 (w), 586 (s), 556 (s), 543 (m). MS (EI, 70 eV): m/z (%) = 296
(100) [M]+, 295 (19), 265 (16), 264 (11), 263 (10), 238 (15), 233
(16). HRMS (EI) calcd. for C19H14OF2 [M]+: 296.10072; found
296.09998.
˜
difluorobenzene (5a):
Starting with
1.11 mmol), Pd(PPh3)4 (3 mol%), 4-methylboronic acid
(100 mg, 0.74 mmol), 2,4-dimethoxyphenylboronic acid
(161 mg, 0.88 mmol), 1,4-dioxane (4 mL), and 5a was isolated
as a colorless highly viscous oil (140 mg, 56%). 1H NMR (300 MHz,
1 (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
CDCl3):
d = 2.19 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 3.69 (s, 3H,
OCH3), 6.17 (d, J = 2.3 Hz, 1H, Ar), 6.32 (dd, J = 8.3, 2.3 Hz, 1H, Ar),
6.74–6.83 (m, 2H, Ar), 6.86–6.91 (m, 5H, Ar). 13C NMR
5.4. 1-(20-Methoxyphenyl)-2-(400-methylphenyl)-3,5-
(62.89 MHz, CDCl3):
d
= 21.2 (CH3), 55.0 (OCH3), 55.3 (OCH3),
difluorobenzene (5d):
98.4 (CH), 102.5 (t, J = 26.3 Hz, CH), 104.1 (CH), 113.6 (dd, J = 21.9,
3.6 Hz, CH), 121.5 (t, J = 2.8 Hz, C), 125.7 (dd, J = 15.3, 3.6 Hz, C),
128.1 (2CH), 130.0 (2CH), 131.1 (C), 131.6 (CH), 136.4 (C), 141.2
(dd, J = 9.6, 4.5 Hz, C), 157.0 (C), 159.8 (dd, JCF = 246.8, 13.0 Hz,
CF), 160.6 (C), 161.1 (dd, JCF = 247.1, 13.4 Hz, C). 19F NMR
Starting with
1 (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
1.11 mmol), Pd(PPh3)4 (3 mol%), 2-methylphenylboronic acid
(100 mg, 0.74 mmol), 1,4-dioxane (4 mL), and 4-methylphenyl-
boronic acid (123 mg, 0.89 mmol), 5d was isolated as a colorless
solid (142 mg, 62%). Mp 67–69 8C. 1H NMR (300 MHz, CDCl3):
(282.4 MHz, CDCl3):
d
= ꢀ111.86 (CF), ꢀ112.9 (CF). IR (ATR):

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
27
d
= 2.14 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 6.72–6.88 (m, 6H, ArH),
5.7. 1-(40-Fluorophenyl)-2-(400-chlorophenyl)-3,5-difluorobenzene
(5g):
6.93–6.97 (m, 1H, ArH), 7.06–7.23 (m, 2H, ArH), 7.23–7.37 (m, 1H,
ArH). 13C NMR (62.89 MHz, CDCl3):
d = 21.2 (CH3), 55.0 (OCH3),
102.8 (CH), 110.7 (t, J = 26.3 Hz, CH), 115.0 (CH), 120.3 (CH), 128.0
(CH), 128.1 (CH), 129.2 (CH), 130.10 (CH), 131.2 (C), 133.6 (C),
156.0 (C), 157.7 (C), 159.2 (C), 159.6 (d, J = 13.8 Hz, C), 159.9 (dd,
JCF = 248.0, 13.0 Hz, CF), 161.1 (dd, JCF = 247.0, 13.4 Hz, C). 19F NMR
Starting with
1
(200 mg, 0.74 mmol), Cs2CO3 (359 mg,
1.11 mmol), Pd(PPh3)4 (3 mol%), 4-fluorophenylboronic acid
(103 mg, 0.74 mmol), 1,4-dioxane (4 mL), and 4-chlorophenyl-
boronic acid (138 mg, 0.89 mmol), 5g was isolated as colorless
highly viscous oil (106 mg, 45%) 1H NMR (300 MHz, CDCl3):
(282.4 MHz, CDCl3):
d
= ꢀ111.86 (CF), ꢀ112.9 (CF). IR (ATR):
˜
V ¼ 3082 ðwÞ, 3053 (w), 3008 (w), 2978 (w), 2928 (w), 2835 (w),
1600 (m), 1558 (w), 1495 (m), 1445 (m), 1394 (m), 1333 (m), 1283
(m), 1241 (s), 1201 (m), 1159 (m), 1091 (m), 1025 (m), 995 (m), 937
(m), 893 (w), 837 (m), 803 (m), 782 (m), 742 (m), 700 (m), 640 (m),
573 (m), 541 (m), 530 (m). MS (EI, 70 eV): m/z (%) = 310 (100) [M]+,
295 (24), 279 (29), 264 (27), 262(10). HRMS (EI) calcd. for
d
= 6.93–7.13 (m, 8H, ArH), 7.23–7.32 (m, 2H, ArH). 13C NMR
(75 MHz, CDCl3): = 102.8 (t, JCF = 3.5 Hz, CH), 103.2 (t, JCF = 3.5 Hz,
d
CH), 103.6 (t, JCF = 3.51 Hz, CH), 112.6 (dd, JCF = 20.4, 4.2 Hz, CH),
115.3 (dd, JCF = 20.7, 4.9 Hz, CH), 123.4 (t, JCF = 2.8 Hz, CH), 128.5
(m, CH), 130.9 (CH), 131.2 (CH), 132.3 (C), 135.9 (dd, JCF = 238.1,
1
14.6 Hz, CF), 143.4 (C), 160.1 (dd, JCF = 245.1, 14.6 Hz, CF), 161.9
1
C
20H16OF2 [M]+: 310.11637; found 310.11557.
(dd, JCF = 251.2, 13.6 Hz, CF).19
F
NMR (282 MHz, CDCl3):
d
˜
= ꢀ110.46 (CF), ꢀ110.99 (CF), ꢀ114.19 (CF). IR (ATR, cmꢀ1):
5.5. 1-(20,50-Dimethoxyphenyl)-2-(400-methylphenyl)-3,5-
V ¼ 3086 ðwÞ, 3052 (w), 1896 (w), 1606 (m), 1582 (s), 1511 (s),
1457 (s), 1392 (m), 1336 (m), 1298 (w), 1222 (s), 1159 (m), 1119
(m), 1091 (s), 1015 (m), 960 (w), 901 (w), 872 (m), 827 (s), 758 (m),
712 (w), 645 (w), 595 (m), 576 (s), 532 (m). MS (EI, 70 eV): m/z
(%) = 318 (100) [M]+, 284 (11), 283 (66), 282 (54), 280 (18), 264
(12), 263 (53). HRMS (EI) calcd. for C18H10ClF3 [M]+: 318.04176;
found 318.041545.
difluorobenzene (5e):
Starting with
1 (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
1.11 mmol), Pd(PPh3)4 (3 mol%), 2,6-dimethoxyphenylboronic
acid (134 mg, 0.74 mmol), 1,4-dioxane (4 mL), and 4-methyl-
boronic acid (121 mg, 0.89 mmol), 5e was isolated as a colorless
highly viscous oil (150 mg, 60%). 1H NMR (300 MHz, CDCl3):
d
= 2.19 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 3.69 (s, 3H, OCH3), 6.17 (d,
J = 2.64 Hz, 1H, Ar), 6.34 (dd, J = 8.4, 2.9 Hz, 1H, Ar), 6.74–6.93 (m,
7H, Ar). 13C NMR (62.89 MHz, CDCl3):
= 21.2 (CH3), 55.0 (OCH3),
6. General procedure for Suzuki–Miyaura reactions (7a–n, 8a–
h):
d
55.3 (OCH3), 98.4 (CH), 102.6 (t, J = 27.3 Hz, CH), 104.1 (CH), 113.6
(dd, J = 20.8, 3.7 Hz, CH), 121.5 (q, J = 3.71 Hz, C), 125.7 (dd,
J = 15.3, 4.0 Hz, C), 128.2 (2CH), 128.6 (d, J = 19.8 Hz, C), 130.1
(CH), 131.1 (CH), 136.4 (C), 141.2 (dd, J = 9.6, 4.5 Hz, C), 157.0 (C),
159.8 (dd, JCF = 248.3, 13.2 Hz, CF), 161.1 (dd, JCF = 248.3, 13.2 Hz,
A 1,4-dioxane solution (4 mL per 0.3 mmol of 6) of 6, Cs2CO3,
Pd(PPh3)4 and arylboronic acid 2 were stirred at 90 8C for 6 or 8 h.
After cooling to room temperature, the organic and the aqueous
layers were separated and the latter was extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ111.52 (CF), ꢀ112.49 (CF).
˜
IR (ATR): V ¼ 3081 ðwÞ, 3054 (w), 2999 (w), 2956 (w), 2835 (w),
1609 (s), 1586 (s), 1508 (s), 1454 (s), 1436 (m), 1425 (m), 1401 (m),
1335 (w), 1303 (s), 1265 (m), 1207 (s), 1184 (w), 1158 (s), 1145 (s),
1092 (s), 1031 (s), 996 (s), 936 (m), 861 (m), 834 (m), 818 (s), 796
(s), 733 (m), 663 (m), 608 (m), 587 (m), 530 (m) cmꢀ1. MS (EI,
70 eV): m/z (%) = 340 (100) [M]+, 294 (11), 265 (14), 238 (11).
HRMS (EI) calcd. for C21H19F2O2 [M]+: 340.12694; found
340.12683.
6.1. 1,4-Di(40-methylphenyl)-2-fluorobenzene (7a):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(106 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7a was isolated as a
colorless solid (65 mg, 60%). Mp 178–180 8C. 1H NMR (300 MHz,
CDCl3):
3H, CH), 7.31–7.35 (m, 4H, CH). 13C NMR (75 MHz, CDCl3):
= 21.2, 21.3 (CH3), 114.4 (d, J = 24.0 Hz, CH), 122.7 (d,
d = 2.33 (s, 6H, CH3), 7.15–7.18 (m, 4H, CH), 7.20–7.31 (m,
5.6. 1-(20,40-Dimethoxyphenyl)-2-(400-methylphenyl)-3,5-
difluorobenzene (5f):
d
J = 12.0 Hz, CH), 126.8, 126.8 (CH), 127.4 (d, J = 13.5 Hz, C),
128.8, 128.9 (CH), 129.3 (CH), 129.7 (CH), 130.9 (d, J = 4.5 Hz, CH),
132.7 (C), 136.7 (C), 137.6, 137.6 (C), 137.8, 137.8 (C), 142.0 (d,
Starting with
1 (200 mg, 0.74 mmol), Cs2CO3 (359 mg,
1.11 mmol), Pd(PPh3)4 (3 mol%), 2,4-dimethoxyphenylboronic
acid (134 mg, 0.74 mmol), 1,4-dioxane (4 mL), and 4-methylboro-
nic acid (121 mg, 0.89 mmol), 5f was isolated as a colorless highly
viscous oil (121 mg, 48%). 1H NMR (300 MHz, CDCl3):
3H, CH3), 3.32 (s, 3H, OCH3), 3.69 (s, 3H, OCH3), 6.17 (d, J = 2.3 Hz,
1H, Ar), 6.32 (dd, J = 8.3, 2.3 Hz, 1H, Ar), 6.74–6.83 (m, 2H, Ar),
6.86–6.91 (m, 5H, Ar). 13C NMR (62.89 MHz, CDCl3):
d = 21.2 (CH3),
1
J = 7.5 Hz, C), 160.1 (d, JCF = 246.0 Hz, CF). 19F NMR (282 MHz,
˜
CDCl3):
d
= ꢀ115.21. IR (ATR, cmꢀ1): V ¼ 2916 ðwÞ, 1912 (w),
d
= 2.19 (s,
1614 (w), 1570 (w), 1545 (w), 1484 (w), 1392 (w), 1118 (M),
1133 (m), 1041 (m), 1005 (w), 948 (w), 890 (w), 844 (w), 807 (w),
731 (w), 646 (w), 557 (m), 496 (w), 455 (w). GC–MS (EI, 70 eV):
m/z (%) = 276 (100) [M]+, 275 (13), 239 (5), 183 (7), 137 (4). HRMS
(EI, 70 eV) calcd. for C20H17F [M]+: 276.13008; found 276.13032.
55.0 (OCH3), 55.3 (OCH3), 98.4 (CH), 102.5 (t, J = 26.3 Hz, CH), 104.1
(CH), 113.6 (dd, J = 21.9, 3.6 Hz, CH), 121.5 (t, J = 2.8 Hz, C), 125.7
(dd, J = 15.3, 3.6 Hz, C), 128.1 (2CH), 130.0 (2CH), 131.1 (C), 131.6
(CH), 136.4 (C), 141.2 (dd, J = 9.6, 4.5 Hz, C), 157.0 (C), 159.8 (dd,
JCF = 246.8, 13.0 Hz, CF), 160.6 (C), 161.1 (dd, JCF = 247.1, 13.4 Hz,
6.2. 1,4-Di(40-methoxyphenyl)-2-fluorobenzene (7b):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
C). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ111.86 (CF), ꢀ112.9 (CF). IR
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(106 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7b was isolated as a
light yellow solid (42 mg, 52%). Mp 182–184 8C. 1H NMR (300 MHz,
˜
(ATR): V ¼ 3080 ðwÞ, 2998 (w), 2956 (w), 2836 (w), 1736 (w), 1609
(s), 1586 (s), 1508 (s), 1454 (s), 1425 (m), 1401 (m), 1372 (w), 1303
(s), 1255 (m), 1184 (w), 1158 (s), 1145 (s), 1092 (s), 1032 (s), 996
(s), 925 (m), 861 (w), 834 (m), 818 (s), 796 (m), 736 (w), 718 (w),
663 (w), 607 (w), 587 (m) cmꢀ1. MS (EI, 70 eV): m/z (%) = 340 (100)
[M]+, 294 (11), 265 (13), 238 (12). ESI-HRMS calcd. for C21H19F2O2
[M + H]+: 341.1348; found 341.1348.
CDCl3):
d
= 3.79 (s, 6H, OCH3), 6.91–6.94 (m, 4H, CH), 7.19–7.29 (m,
= 55.4,
3H, CH), 7.36–7.46 (m, 4H, CH). 13C NMR (75 MHz, CDCl3):
d
55.4 (OCH3), 114.0, 114.0 (CH), 114.3, 114.3 (CH) 114.4 (d,
J = 20.0 Hz, CH), 122.4 (d, J = 3.0 Hz, CH), 128.2, 128.2 (CH), 130.1
(d, J = 3.0, 2C, CH), 130.7 (d, J = 4.5 Hz, CH), 130.9, 130.9 (C),

28
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
1
= ꢀ114.8 (CF). IR (ATR, cmꢀ1): V ¼ 3103 ðwÞ, 3058 (w),
˜
132.1,132.1 (C), 142.0 (d, J = 7.5 Hz, C), 158.6 (d, JCF = 248.0 Hz,
CDCl3): d
CF), 159.2, 159.6 (C). 19F NMR (282 MHz, CDCl3):
d
= ꢀ114.88. IR
3006 (w), 2962 (w), 2838 (w), 1621 (w), 1598 (w), 1579 (w), 1515
(w), 1402 (w), 1316 (w), 1264 (m), 1199 (w), 1133 (w), 1113 (m),
1085 (m), 1019 (w), 934 (w), 875 (w), 824 (w), 787 (m), 734 (m),
651 (w), 581 (w), 535 (m). MS (EI, 70 eV): m/z (%) = 368 (100) [M]+,
338 (36). HRMS (EI) calcd. for C22H21O4F1 [M]+: 368.14184; found
368.12418.
(ATR, cmꢀ1): V ¼ 3035 ðwÞ, 3016 (w), 2960 (w), 2933 (w), 2909 (w),
2836 (w), 1605 (s), 1578 (m), 1476 (m), 1391 (m), 1292 (m), 1030
(m), 871 (m), 807 (s), 6963 (w), 578 (m), 522 (m), 456 (m). GC–MS
(EI, 70 eV); m/z (%) = 308 (100) [M]+, 293 (40), 265 (11), 222 (10),
154 (7), 133 (5). HRMS (EI) calcd. for C20H17FO2 [M]+: 308.12071;
found 308.12022.
˜
6.6. 1,4-Di(40-vinylebutylphenyl)-2-fluorobenzene (7f):
6.3. 1,4-Di(40-ethoxyphenyl)-2-fluorobenzene (7c):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (263 mg,
Starting with
6
(100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-vinylphenylboronic acid
(115 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7f was isolated as
a colorless solid (53 mg, 45%). Mp stable upto 375 8C. 1H NMR
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid
(64 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 7c was isolated as a
colorless solid (86 mg, 65%). Mp 96–98 8C. 1H NMR (300 MHz,
(300 MHz, CDCl3):
J = 17.7, 2H, CH2), 6.70 (q, J = 17.6 Hz, 2H, CH), 7.30–7.54 (m, 11H,
ArH). 13C NMR (75.46 MHz, CDCl3):
= 29.6 (CH3), 114.3 (CH),
d = 5.23 (dt, J = 10.87 Hz, 2H, CH2), 5.75 (q,
CDCl3):
OCH2), 6.85–6.91 (m, 4H, CH), 7.21–7.28 (m, 3H, CH), 7.36–7.50 (m,
4H, CH). 13C NMR (75 MHz, CDCl3):
= 14.9 (2CH3), 63.6 (2OCH2),
d = 1.39 (t, J = 7.2 Hz, 6H, CH3), 3.99 (q, J = 6.89 Hz, 4H,
d
d
126.3 (2CH), 126.8 (2CH), 127.0 (2CH), 129.0 (2CH), 129.7 (2CH),
130.8 (d, J = 3.89 Hz, C), 133.1 (C), 136.2 (C), 136.4 (C), 136.9 (C),
137.2 (t, J = 2.39 Hz, C), 153.1 (d, JCF = 237.0 Hz, CF). 19F NMR
106.8 (d, J = 22.0 Hz, C), 114.5 (d, J = 16.5 Hz, CH), 114.7 (CH), 115.0
(CH), 123.4 (d, J = 3.8 Hz, CH), 127.7 (CH), 128.0 (CH), 131.3 (C),
133.6 (CH), 133.9 (C), 144.1 (C), 159.2 (d, JCF = 247.0 Hz, C). 19F
1
(282.4 MHz, CDCl3): d ꢀ117.50 (CF). IR (ATR, cmꢀ1): V ¼ 2922 ðmÞ,
˜
= ꢀ114.92. IR (ATR, cmꢀ1): V ¼ 2958 ðwÞ,
2852 (m), 1740 (w), 1696 (w), 1604 (w), 1547 (w), 1486 (w), 1395
(w), 1242 (w), 1185 (w), 1134 (w), 1045 (w), 1006 (w), 893 (w), 878
(w), 814 (w), 771 (w), 700 (w), 580 (w), 548 (w). MS (EI, 70 eV): m/z
(%) = 300 (100) [M]+. HRMS (EI) calcd. for C22H17F [M]+: 300.13088;
found 300.13021.
˜
NMR (282 MHz, CDCl3):
d
2935 (w), 2838 (w), 1897 (w), 1597 (m), 1474 (s), 1243 (s), 1180
(m), 1027 (s), 805 (s), 751 (m), 692 (m), 412 (w). GC–MS (EI, 70 eV):
m/z (%) = 336 (100) [M]+, 307 (22), 280 (32), 279 (15), 251 (14).
HRMS (EI) calcd. for C22H21FO2 [M]+: 336.15201; found 336.15196.
6.4. 1,4-Di(30,40-dimethoxyphenyl)-2-fluorobenzene (7d):
6.7. 1,4-Di(40-tert-butylphenyl)-2-fluorobenzene (7g):
Starting with
6
(100 mg, 0.39 mmol), Cs2CO3 (263 mg,
Starting with 6 (100 mg, 0.39 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 3,4-dimethoxyphenylboronic
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-tert-butylphenylboronic acid
(138 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7g was isolated as a
colorless solid (89 mg, 63%). Mp 184–186 8C. 1H NMR (300 MHz,
acid (141 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7d was isolated
as a colorless oil (84 mg, 58%). 1H NMR (300 MHz, CDCl3):
d = 3.84
(s, 6H, OCH3), 3.85 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.24–6.65 (m,
1H, ArH), 6.86–6.91 (m, 2H, ArH), 6.99 (m, 3H, ArH), 7.23–7.42 (m,
CDCl3):
7.36–7.42 (m, 6H, ArH), 7.45–7.50 (m, 4H, ArH). 13C NMR
(75.46 MHz, CDCl3): = 31.3 (CH3), 34.6 (C), 111.3 (CH), 114.3
d = 1.29 (s, 18H, CH3), 7.30 (dd, J = 12.1, 1.6 Hz, 1H, ArH),
3H, ArH). 13C NMR (75.46 MHz, CDCl3):
d
= 55.8 (OCH3), 55.9
d
(2OCH3), 56.5 (OCH3), 100.5 (CH), 100.7 (CH), 110.1 (CH), 111.3 (d,
J = 19.9 Hz, CH), 112.3 (t, J = 3.5 Hz, CH), 114 (d, J = 23.9 Hz, CH),
119.3 (CH), 128.2 (C), 130.6 (d, J = 4.3 Hz, CH), 132.4 (d, J = 2.4 Hz,
C), 134.7 (C), 141.7 (d, J = 8.1 Hz, C), 143.1 (C), 148.8 (d, J = 3.23 Hz,
(d, J = 23.9 Hz, CH), 122.7 (d, J = 3.2 Hz, CH), 125.4 (2CH), 125.9
(2CH), 126.6 (2CH), 127.3 (d, J = 13.6 Hz, C), 128.6 (d, J = 3.2 Hz,
CH), 130.8 (d, J = 4.3 Hz, C), 132.6 (d, J = 1.4 Hz, CH), 136.7 (d,
J = 1.9 Hz, C), 141.8 (C), 141.9 (C), 150.8 (d, JCF = 19.3 Hz, C), 160.1
C), 149.1 (C), 149.3 (C), 159.9 (d, J = 247.1 Hz, CF). 19F NMR
(d, JCF = 247 Hz, C). 19F NMR (282.4 MHz, CDCl3):
d = 117.97 (CF). IR
= ꢀ117.7 (CF). IR (ATR, cmꢀ1): V ¼ 3103 ðwÞ,
(ATR, cmꢀ1): V ¼ 3033 ðwÞ, 2950 (m), 2860 (w), 2705 (w), 2163
(w), 1977 (w), 1910 (w), 1741 (w), 1616 (w), 1543 (w), 1486 (m),
1428 (w), 1394 (m), 1305 (w), 1261 (m), 1200 (w), 1187 (m), 1122
(w), 1045 (w), 1004 (w), 948 (w), 894 (m), 816 (s), 829 (w), 750 (w),
675 (w), 586 (m), 548 (m). MS (EI, 70 eV): m/z (%) = 360 (54) [M]+,
346 (26), 345 (100), 137 (12). HRMS (EI) calcd. for C26H29F[M]+:
360.22478; found 360.22419.
˜
˜
(282.4 MHz, CDCl3):
d
3072 (w), 2996 (w), 2931 (w), 2833 (w), 2732 (w), 2700 (w), 2583
(w), 2551 (w), 2457 (w), 2400 (w), 2353 (w), 2277 (w), 2052 (w),
1907 (w), 1797 (w), 1737 (w), 1621 (w), 1578 (m), 1536 (w), 1498
(w), 1467 (s), 1426 (s), 1404 (s), 1354 (w), 1318 (m), 1259 (s), 1226
(s), 1197 (m), 1137 (m), 1104 (s), 1084 (m), 1035 (m), 1001 (s), 966
(m), 920 (m), 879 (m), 850 (m), 820 (s), 787 (s), 744 (s), 692 (s), 657
(m), 606 (m), 570 (m), 536 (m). MS (EI, 70 eV): m/z (%) = 368 (100)
[M]+, 338 (35). HRMS (EI) calcd. for C22H21O4F [M]+: 368.14184;
found 368.14198.
6.8. 1,4-Di(40-acetylphenyl)-2-fluorobenzene (7h):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (263 mg,
6.5. 1,4-Di(20,40-dimethoxyphenyl)-2-fluorobenzene (7e):
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-acetylphenylboronic acid
(127 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7h was isolated as
a colorless solid (68 mg, 52%). Mp 178–180 8C.1H NMR (300 MHz,
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2,4-dimethoxyphenylboronic
acid (141 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7e was isolated
as a colorless semi solid (91 mg, 63%). 1H NMR (300 MHz, CDCl3):
CDCl3):
4H, ArH), 7.97–8.00 (m, 4H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 26.7 (CH3), 29.7 (CH3), 114.8 (CH), 115 (d, J = 2.3 Hz, CH), 123.3
d = 2.58 (s, 6H, CH3), 7.37–7.53 (m, 3H, ArH), 7.61–7.66 (m,
d
d
= 3.60 (s, 3H, OCH3), 3.63 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 3.86 (s,
3H, OCH3), 6.86–6.95 (m, 4H, ArH), 7.03–7.09 (m, 2H, ArH), 7.28–
7.34 (m, 3H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 55.9 (OCH3),
(d, J = 3.6 Hz, CH), 127.31 (2CH), 128.6 (2CH), 129.0 (CH), 129.2
(CH), 130.9 (CH), 131.9 (d, J = 4.3 Hz, CH), 136.3 (C), 136.5 (C), 139.9
(d, J = 1.3 Hz, C), 141.8 (d, J = 7.8 Hz, C), 143.6 (d, J = 1.8 Hz, C), 160.6
d
56.0 (OCH3), 60.7 (OCH3), 60.8 (OCH3), 112.0 (CH), 112.4 (CH),
122.5 (CH), 123.3 (d, J = 2.6 Hz, CH), 123.7 (CH), 124.2 (CH), 124.6
(d, J = 3.9 Hz, C), 130.1 (C), 131.4 (d, J = 3.7 Hz, CH), 134.5 (d,
J = 2.0 Hz, C), 139.4 (d, J = 8.3 Hz, C), 146.9 (d, J = 52.3 Hz, C), 153.1
(d, J = 29.3 Hz, C), 159.4 (d, J = 247.2 Hz, CF). 19F NMR (282.4 MHz,
(d, J = 249.5 Hz, CF), 197.6 (CO), 197.8 (CO). 19F NMR (282.4 MHz,
˜
CDCl3):
d
= ꢀ116.6 (CF). IR (ATR, cmꢀ1): V ¼ 3039 ðwÞ, 2921 (w),
2852 (w), 2387 (w), 2325 (w), 1731 (w), 1678 (m), 1602 (w), 1563
(w), 1520 (w), 1484 (w), 1423 (w), 1392 (w), 1357 (w), 1289 (w),
1264 (m), 1184 (m), 1112 (w), 1052 (w), 1005 (w), 961 (w), 877

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
29
(w), 811 (m), 754 (w), 691 (w), 623 (m), 592 (m), 531 (w). MS (EI,
6.12. 1,4-Di(30-chlorophenyl)-4-fluorobenzene (7l):
70 eV): m/z (%) = 332 (51) [M]+, 318 (22), 317 (100), 244 (11).
HRMS (EI) calcd. for C22H17FO2 [M]+: 332.12126; found 332.12776.
Starting with (200 mg, 0.79 mmol), Cs2CO3 (385 mg,
6
1.81 mmol), Pd(PPh3)4 (3 mol%), 3-chlorophenylboronic acid
(246 mg, 1.58 mmol) and 1,4-dioxane (4 mL), 7l was isolated as
a colorless solid (201 mg, 80%). Mp 102–103 8C. 1H NMR (300 MHz,
6.9. 1,3-Di(40-fluorphenyl)-5-fluorobenzene (7i):
Starting with
6
(100 mg, 0.37 mmol), Cs2CO3 (263 mg,
CDCl3):
7.43 (m, 3H, ArH), 7.49–7.52 (m, 2H, ArH). 13C NMR (75 MHz,
CDCl3): = 114.8 (d, J = 25.7 Hz, CH), 123.0 (d, J = 4.0 Hz, CH), 125.1
(CH), 127.1 (2CH), 128.0 (d, J = 9.4 Hz, 2CH), 129.0 (d, J = 4.0 Hz,
CH), 130.0 (d, J = 33.7 Hz, 2CH), 131.0 (d, J = 4.0 Hz, CH), 134.4 (C),
134.9 (C), 137.0 (C), 141.1 (C), 141.4 (C), 141.5 (C), 159.9 (d,
d = 7.25–7.33 (m, 5H, ArH), 7.34–7.35 (m, 1H, ArH). 7.37–
0.81 mmol), Pd(PPh3)4 (3 mol%), 4-fluoromethylphenylboronic
acid (109 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7i was isolated
as a colorless solid (54 mg, 48%). Mp 145–149 8C. 1H NMR
(300 MHz, CDCl3):
ArH), 7.32–7.36 (m, 4H, ArH), 7.41–7.50 (m, 4H, ArH). 13C NMR
(75 MHz, CDCl3): = 114.5 (dd, J = 24.2, 3.8 Hz, CH), 115.5 (d,
J = 21.5 Hz, CH), 115.9 (d, J = 21.4 Hz, CH), 122.8 (t, J = 3.2 Hz, CH),
128.2 (CH), 128.8 (CH), 129.2 (CH), 130.5 (d, J = 3.34 Hz, CH), 130.7
(dd, J = 8.2, 3.3 Hz, CH), 130.9 (d, J = 3.3 Hz, CH), 131.3 (CH), 133.7
(d, J = 1.1 Hz, C), 134.2 (d, J = 4.9 Hz, C), 137.8 (d, J = 1.7 Hz, C), 141.1
(d, J = 8.3 Hz, C), 159.9 (d, JCF = 248.2 Hz, CF), 162.5 (d,
JCF = 247.6 Hz, CF), 168.8, (d, JCF = 247.7 Hz, CF). 19F NMR
d
d = 7.03–7.09 (m, 2H, ArH), 7.24–7.29 (m, 1H,
d
JCF = 248.8 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ114.6 (CF). IR
(ATR, cmꢀ1): V ¼ 3066 ðwÞ, 2923 (w), 2851 (w), 1619 (m), 1562
(m), 1463 (m), 1386 (s), 1288 (m), 1248 (m), 1186 (m), 1130 (m),
1079 (m), 1022 (m), 967 (m), 915 (m), 876 (m), 824 (m), 773 (s),
˜
756 (s), 686 (s), 636 (m), 552 (m), 515 (m), 468 (m), 419 (m) cmꢀ1
.
GC–MS (EI, 70 eV): m/z (%) = 292 (100) [M]+, 277 (34), 249 (23), 233
(12). HRMS (EI) calcd. for C18H11Cl2F [M]+: 316.02164; found
316.021941; calcd. for C18H11Cl37ClF [M]+: 318.01869; found
318.01898.
(282 MHz, CDCl3):
d
= ꢀ114.2.5, ꢀ117.3, ꢀ117.6 (CF). IR (ATR,
cmꢀ1): V ¼ 3070 ðwÞ, 3041 (w), 2953 (w), 2917 (w), 2849 (w), 1907
(w), 1602 (w), 1595 (w), 1524 (w), 1480 (m), 1429 (w), 1387 (w),
1298 (w), 1224 (m), 1163 (m), 1094 (w), 1006 (w), 967 (w), 892
(m), 833 (m), 809 (s), 751 (w), 709 (w), 690 (w), 613 (w), 577 (m),
546 (w). MS (EI, 70 eV); m/z (%) = 284 (100) [M]+. HRMS (EI) calcd.
for C18H11F3 [M]+: 284.08074; found 284.10827.
˜
6.13. 1-(40-Ethylphenyl)-4-(400-ethylphenyl)-2-fluorobenzene (7m):
Starting with
6 (200 mg, 0.79 mmol), Cs2CO3 (385 mg,
1.81 mmol), Pd(PPh3)4 (3 mol%), 4-ethylphenylboronic acid
(237 mg, 1.58 mmol) and 1,4-dioxane (4 mL), 7m was isolated
as a colorless solid (195 mg, 81%). Mp 111 8C. 1H NMR (300 MHz,
6.10. 1,4-Di(30-methylphenyl)-2-fluorobenzene (7j):
CDCl3):
7.5 Hz, 3H, CH3), 2.62 (t, J = 15.1 Hz, 7.4 Hz, 4H, 2CH2), 7.19–7.22
(m, 4H, ArH), 7.27–7.40 (m, 3H, ArH), 7.42–7.47 (m, 4H, ArH). 13
NMR (75 MHz, CDCl3): = 15.6 (d, J = 2.2 Hz, 2CH3), 28.6 (d,
J = 5.5 Hz, 2CH2), 114.4 (CH), 114.5 (CH), 122.7 (d, J = 4.0 Hz, CH),
126.9 (2CH), 127.4 (d, J = 13.8 Hz, C), 128. (2CH), 128.5 (2CH), 128.9
(d, J = 4.0 Hz, CH), 130.8 (d, J = 4.0 Hz, CH), 132.9 (C), 136.9 (C),
141.9 (d, J = 8.3 Hz, C), 143.9 (d, J = 20.9 Hz, CH), 160.1 (d,
d = 1.20 (t, J = 15.2 Hz, 7.5 Hz, 3H, CH3), 1.22 (t, J = 15.2 Hz,
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 3-methylphenylboronic acid
(106 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 7j was isolated as a
colorless solid (65 mg, 60%). Mp 180–182 8C. 1H NMR
(300 MHz,CDCl3):
ArH), 7.26–7.37 (m, 2H, ArH), 7.42 (t, J = 7.2 Hz, 5H, ArH). 13C NMR
(75 MHz, CDCl3): = 21.1, 21.2 (CH3), 114.1 (d, J = 23.8 Hz, CH),
C
d
d = 2.33 (s, 6H, CH3), 7.19 (d, J = 8.1 Hz, 4H,
d
122.6 (d, J = 3.2 Hz, CH), 126.8 (2CH), 127.5 (d, J = 3.2 Hz, C), 128.7 (d,
J = 3.2 Hz, 2CH), 129.2 (2CH), 129.6 (2CH), 130.7 (d, J = 4.0 Hz, CH),
132.6 (C), 136.7 (d, J = 18.0 Hz, C), 137.5 (d, J = 14.6 Hz, C), 147.9 (d,
JCF = 247.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ117.24 (CF).
IR (ATR, cmꢀ1): V ¼ 3027 ðwÞ, 2963 (w), 2873 (w), 2361 (w), 1609
(w), 1544 (w), 1485 (w), 1428 (w), 1394 (w), 1295 (w), 1260 (w),
1180 (w), 1135 (w), 1050 (w), 1004 (w), 970 (w), 889 (w), 814 (w),
728 (w), 696 (w), 641 (w), 582 (w), 499 (w), 417 (w) cmꢀ1. GC–MS
(EI, 70 eV): m/z (%) = 304 (100) [M]+, 290 (18), 289 (80), 274 (21),
137 (17). HRMS (ESI) calcd. for C22H22F [M + H]+: 305.17001; found
305.16948. Anal. calcd. for C21H17FO2: C,86.85. H, 6.91. Found: C,
86.82. H, 6.88.
˜
J = 8.2 Hz, C), 160.0 (d, J = 246.8 Hz, CF). 19F NMR (282 MHz, CDCl3):
˜
d
= ꢀ117.97. IR (ATR, cmꢀ1): V ¼ 3027 ðwÞ, 2917 (w), 2853 (w), 2735
(w), 1914 (w), 1614 (w), 1569 (w), 1547 (w), 1423 (w), 1392 (w),
1296 (w), 1215 (w), 1182 (w), 1133 (w), 1042 (w), 1005 (w), 947 (w),
890 (w), 869(w), 807 (m), 731 (w), 647(w), 557(w), 556(w). GC–MS
(EI, 70 eV); m/z (%) = 276 (100) [M]+, 275 (11). HRMS (EI) calcd. for
C
20H17F [M]+: 276.13008; found 276.13109.
6.11. 1,4-Di(2-thienyl)-2-fluorobenzene (7k):
Starting with (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
6.14. 1,4-Di(20,50-dimethoxyphenyl)-2-fluorobenzene (7n):
Starting with
6 (200 mg, 0.79 mmol), Cs2CO3 (385 mg,
6
1.81 mmol), Pd(PPh3)4 (3 mol%), 2,5-dimethoxyphenylboronic
acid (287 mg, 1.58 mmol) and 1,4-dioxane (4 mL), 7n was
isolated as a colorless solid (221 mg, 76%). Mp 95–97 8C. 1H NMR
0.50 mmol), Pd(PPh3)4 (3 mol%), 2-thienylboronic acid (49 mg,
0.39 mmol) and 1,4-dioxane (4 mL), 7k was isolated as a colorless
solid (51 mg, 50%). Mp 94–96 8C. 1H NMR (300 MHz, CDCl3):
(300 MHz, CDCl3):
(s, 3H, OCH3), 3.72 (s, 3H, OCH3), 6.76–6.87 (m, 6H, ArH), 7.25–
7.33 (m, 3H, ArH). 13C NMR (75 MHz, CDCl3):
= 55.8 (2OCH3),
d = 3.69 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.71
d
= 7.00–7.06 (m, 2H, ArH), 7.22–7.34 (m, 5H, ArH), 7.41–7.43 (m,
1H, ArH), 7.52–7.57 (m, 1H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 113.4 (d, J = 24.5 Hz, CH), 121.1 (d, J = 13.5 Hz, C), 121.8 (d,
d
d
56.2 (OCH3), 56.4 (OCH3), 112.5 (d, J = 15.2 Hz, 2CH), 113.9 (d,
J = 33.3 Hz, 2CH), 116.5 (2CH), 116.9 (d, J = 25.7 Hz, CH), 124.6
(d, J = 16.4 Hz, C), 124.8 (d, J = 3.0 Hz, CH), 125.8 (C), 130.0 (d,
J = 2.3 Hz, C), 131.3 (d, J = 3.8 Hz, CH), 139.5 (d, J = 8.2 Hz, C),
151.0 (d, J = 45.5 Hz, 2C), 153.6 (d, J = 23.1 Hz, 2C), 159.6 (d,
J = 3.1 Hz, CH), 123.8 (CH), 125.6 (CH), 125.8 (d, J = 4.5 Hz, CH),
126.3 (d, J = 7.1 Hz, CH), 127.8 (CH), 128.3 (CH), 129.0 (d, J = 4.2 Hz,
CH), 134.9 (d, J = 9.4 Hz, C), 136.9 (d, J = 3.87 Hz, C), 142.6 (d,
J = 2.9 Hz, C), 159.2 (d, JCF = 250.2 Hz, CF). 19F NMR (282.4 MHz,
CDCl3):
d
= ꢀ107.4 (CF). IR (ATR, cmꢀ1): V ¼ 3100 ðwÞ, 3074 (w),
JCF = 247.3 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ114.6 (CF).
˜
IR (ATR, cmꢀ1): V ¼ 2991 ðwÞ, 2938 (w), 2832 (w), 1616 (w),
1586 (w), 1487 (m), 1403 (m), 1297 (w), 1257 (m), 1216 (m),
1176 (m), 1119 (m), 1082 (m), 1017 (s), 933 (m), 869 (m), 828
˜
2961 (w), 2854 (w), 1799 (w), 1606 (w), 1553 (w), 1483 (m), 1419
(m), 1354 (w), 1289 (w), 1259 (m), 1207 (w), 1135 (w), 1058 (m),
1015 (m), 945 (w), 866 (m), 805 (s), 692 (s), 630 (m), 579 (w), 550
(m), 528 (m). GC–MS (EI, 70 eV): m/z (%) = 260 (100) [M+], 215 (12).
HRMS (EI) calcd. for C14H9FS2 [M]+: 260.01242; found 260.01269.
(m), 797 (s), 733 (m), 688 (m), 603 (m), 539 (m), 457 (m) cmꢀ1
GC–MS (EI, 70 eV): m/z (%) = 368 (100) [M]+, 339 (12), 338 (59),
.

30
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
169 (12). HRMS (EI) calcd. for C22H22FO4 [M + H]+: 369.14966;
found 369.15000.
6.18. 1-Bromo-4(30,40-di-methoxyphenyl)-2-fluorbenzene(8d):
Starting with (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 3,4-dimethoxyphenylboronic
6
6.15. 1-Bromo-4(40-methylphenyl)-2-fluorobenzene (8a):
acid (71.0 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8d was isolated
Starting with
6
(100 mg, 0.39 mmol), Cs2CO3 (190 mg,
as a colorless oil (82 mg, 67%). 1H NMR (300 MHz, CDCl3):
d = 3.84
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(53 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8a was isolated as a
colorless solid (63 mg, 60%). Mp 81–83 8C. 1H NMR (300 MHz,
(s, 3H, OCH3), 3.86 (s, 3H, OCH3), 6.86–6.89 (m, 1H, CH), 6.96–6.99
(m, 3H, CH), 7.18–7.23 (m, 2H, CH). 13C NMR (75 MHz, CDCl3):
d
= 55.9, 56.0 (OCH3), 110.0 (C), 111.2, 112.1 (CH), 112.1 (CH),
CDCl3):
(m, 1H, ArH), 7.26–7.29 (m, 2H, ArH), 7.40 (dd, J = 1.5 Hz, 1H,
ArH). 13C NMR (75.46 MHz, CDCl3):
= 21.1 (CH3), 107.4 (d,
J = 27.3 Hz, C), 114.8 (d, J = 22.5 Hz, CH), 123.3 (d, J = 3.3 Hz, CH),
126.7 (2CH), 129.7 (2CH), 133.6 (CH), 136.1 (d, J = 1.6 Hz, C),
d
= 2.25 (s, 3H, CH3), 7.05–7.09 (m, 3H, ArH), 7.14–7.18
119.7 (d, J = 3.7 Hz, CH), 121.3 (CH), 121.4 (d, J = 3.0 Hz, CH), 127.6
(CH), 131.5 (C), 131.6 (C), 149.8 (COCH3), 149.9 (COCH3), 158.9 (d,
d
1JCF = 247.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ115.11. IR
(ATR, cmꢀ1): V ¼ 2960 ðwÞ, 2936 (w), 1599 (m), 1581 (m), 1475
(m), 1339 (m), 1243 (m), 1180 (m), 1028 (s), 891 (s), 871 (m), 834
(m), 752 (m), 693 (m), 640 (w), 597 (w), 542 (m), 412 (m). GC–MS
(EI, 70 eV): m/z (%) = 310 (100) [M]+, 295 (18), 269 (16), 267 (18),
188 (66), 173 (11), 157 (15), 145 (18), 106 (8). HRMS (EI) calcd. for
˜
138.2 (C), 142.6 (d, J = 7.1 Hz, C), 159.3 (d, JCF = 246.2 Hz, CF). 19
F
NMR (282.4 MHz, CDCl3):
d
= ꢀ107.4 (CF). IR (ATR, cmꢀ1):
˜
V ¼ 3027 ðwÞ, 2918 (w), 2852 (w), 2732 (w), 2602 (w), 2496 (w),
1907 (w), 1599 (w), 1556 (w), 1472 (w), 1417 (w), 1390 (w),
1301 (w), 1262 (w), 1197 (w), 1137 (w), 1055 (w), 1019 (w), 944
(w), 871 (w), 801 (m), 693 (w), 643 (w), 594 (w), 546 (w), 529
(w). MS (EI, 70 eV): m/z (%) = 266 (100) (81Br) [M]+, 265 (25), 264
(98) (79Br), 263 (12), 185 (17), 184 (19), 183 (48), 170 (18), 165
(26). HRMS (EI) calcd. for C13H10BrF [M]+: 263.99444; found
263.994605. HRMS (EI); calcd. for C13H1081BrF [M]+: 265.99240;
found 265.99281.
C
14H12BrFO2 [M]+: 310.00047; found 310.00098.
6.19. 1-Bromo-4(40-vinylphenyl)-2-fluorobenzene (8e):
Starting with (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
6
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-vinylphenylboronic acid
(57 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8e was isolated as
a colorless solid (49 mg, 45%). Mp 338–340 8C. 1H NMR (300 MHz,
CDCl3):
6.52 (q, J = 3.7 Hz, 1H, CH), 7.00–7.13 (m, 3H, ArH), 7.23–7.35 (m,
4H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 114.5 (CH), 114.9
d = 5.03 (d, J = 2.3 Hz, 1H, CH), 5.58 (d, J = 4.3 Hz, 1H, CH),
6.16. 1-Bromo-4(40-methoxyphenyl)-2-fluorobenzene (8b):
d
Starting with
6
(100 mg, 0.39 mmol), Cs2CO3 (190 mg,
(CH), 123.5 (d, J = 4.3 Hz, CH), 126.4 (CH), 126.8 (CH), 126.9 (CH),
128.9 (d, J = 3.2 Hz, CH), 133.7 (CH), 136.1 (CH), 136.3 (d,
J = 19.6 Hz, C), 137.5 (C), 137.6 (d, J = 2.4 Hz, C), 142.1 (d,
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(59.3 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8b was isolated as
a colorless oil (67 mg, 60%). 1H NMR (300 MHz, CDCl3):
(s, 3H, OCH3), 6.90 (td, J = 8.85, 2.18 Hz, 2H, ArH), 7.20–7.27 (m,
3H, ArH), 7.34–7.39 (m, 2H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 55.3 (OCH3), 114.1 (2CH), 119.6 (d, J = 25.9 Hz, CH), 120.5
(d, J = 9.5 Hz, C), 127.6 (d, J = 3.70 Hz, C), 128.5 (d, J = 12.4 Hz,
CH), 129.9 (d, J = 2.8 Hz, CH), 131.4 (d, J = 4.07 Hz, CH), 131.9
(d, J = 2.77 Hz, C), 132.1 (d, J = 9.8 Hz, CH), 159.4 (C), 159.5
(d, JCF = 251 Hz, C). 19F NMR (282.4 MHz, CDCl3):
(CF). IR (ATR, cmꢀ1): V ¼ 3067 ðwÞ, 2999 (w), 2922 (w), 2835 (w),
2712 (w), 2550 (w), 2158 (w), 2048 (w), 1980 (w), 1891 (w),
1607 (m), 1518 (m), 1477 (s), 1390 (m), 1264 (m), 1247 (s), 1178
(s), 1112 (m), 1037 (m), 963 (w), 869 (s), 807 (s), 719 (m), 636
(w), 570 (m), 539 (s). MS (EI, 70 eV): m/z (%) = 281 (13) [M]+,
280 (100), 267 (30), 265 (31), 239 (29), 158 (15), 157 (35).
HRMS (EI) calcd. for C13H10OBrF [M]+: 281.98731; found
281.98769.
d
= 3.77
J = 7.4 Hz, C), 159.4 (d, JCF = 243.3 Hz, CF). 19F NMR (282.4 MHz,
˜
CDCl3):
d
= ꢀ107.1 (CF). IR (ATR, cmꢀ1): V ¼ 2922 ðwÞ, 2852 (w),
2368 (w), 2165 (w), 2046 (w), 1977 (w), 1711 (m), 1605 (w), 1573
(w), 1521 (w), 1486 (w), 1432 (w), 1359 (m), 1301 (w), 1219 (m),
1186 (w), 1116 (w), 1090 (w), 1006 (w), 989 (w), 905 (w), 878
(w), 814 (m), 771 (w), 721 (w), 668 (w), 622 (w), 578 (w), 529 (w).
MS (EI, 70 eV); m/z (%) = 278 (96) (81Br) [M]+, 276 (100), 277 (18),
196 (41), 170 (14), 158. HRMS (EI) calcd. for C14H1081BrF [M]+:
277.99240; found 277.99241.
d
d
= ꢀ115.31
˜
6.20. 1-Bromo-4(40-tert-butylphenyl)-2-fluorobenzene (8f):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-tert-butylphenylboronic acid
(46 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8f was isolated as a
colorless solid (70 mg, 58%). Mp 75–77 8C. 1H NMR (300 MHz,
CDCl3):
(75.46 MHz, CDCl3):
d
= 1.14 (s, 9H, CH3), 7.02–7.38 (m, 7H, ArH). 13C NMR
6.17. 1-Bromo-4(40-ethoxyphenyl)-2-fluorbenzene (8c):
d = 31.2 (CH3), 34.7 (C), 114.8 (d, J = 22.1 Hz,
CH), 123.6 (d, J = 3.2 Hz, CH), 125.6 (CH), 125.9 (CH), 126.5 (CH),
128.5 (d, J = 3.51 Hz, CH), 131.6 (t, J = 3.7 Hz, C), 133.6 (CH), 136.1
(d, J = 2.3 Hz, C), 142.7 (d, J = 6.9 Hz, C), 151.4 (C), 159.3 (d,
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid
(64.7 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8c was isolated as
a colorless solid (79 mg, 68%). Mp 76–78 8C. 1H NMR (300 MHz,
JCF = 246.7 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ115.01 (CF).
IR (ATR, cmꢀ1): V ¼ 3066 ðwÞ, 2960 (w), 2927 (w), 2866 (w), 2718
(w), 1915 (w), 1892 (w), 1599 (w), 1519 (w), 1477 (m), 1387 (m),
1266 (m), 1245 (m), 1196 (m), 1109 (m), 1053 (m), 967 (w), 873
(m), 810 (s), 716 (w), 643 (w), 575 (m), 545 (s). MS (EI, 70 eV): m/z
(%) = 308 (33)(81Br) [M]+, 306 (32), 293 (100), 292 (16), 291 (99),
265 (17), 212 (15), 183 (18). HRMS (EI) calcd. for C16H1681BrF [M]+:
308.03935; found 308.03949.
˜
CDCl3):
OCH2), 6.85–6.91 (m, 2H, CH), 7.21–7.28 (m, 3H, CH), 7.36–7.50 (m,
2H, CH). 13C NMR (75 MHz, CDCl3):
= 14.9 (CH3), 63.6 (OCH2),
d = 1.37 (t, J = 7.2 Hz, 3H, CH3), 3.99 (q, J = 6.9 Hz, 2H,
d
106.8 (d, J = 22.0 Hz, C), 114.5 (d, J = 16.5 Hz, CH), 114.7 (CH), 115.0
(CH), 123.4 (d, J = 3.8 Hz, CH), 127.7 (CH), 128.0 (CH), 131.3 (C),
133.6 (CH), 133.9 (C), 144.1 (C), 159.2 (d, JCF = 247.0 Hz, C). 19F
1
= ꢀ114.92. IR (ATR, cmꢀ1): V ¼ 2958 ðwÞ,
˜
NMR (282 MHz, CDCl3):
d
2935 (w), 2838 (w), 1897 (w), 1597 (m), 1474 (s), 1243 (s),
1180(m), 1027 (s), 805 (s), 751 (m), 692 (m), 412 (w). GC–MS (EI,
70 eV): m/z (%) = 294 (78) [M]+, 268 (100), 239 (22), 211 (20), 157
(32), 133 (12), 106 (10). HRMS (EI) calcd. for C14H12BrFO [M]+:
294.00556; found 294.00513.
6.21. 1-Bromo-4(30-chlorophenyl)-2-fluorobenzene (8g):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 3-chlorophenylboronic acid
(60 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8g was isolated as a

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
31
colorless solid (56 mg, 50%). Mp 94–95 8C. 1H NMR (300 MHz,
CDCl3): = 7.21 (d, J = 8.7 Hz, 1H, ArH), 7.25–7.33 (m, 2H, ArH),
7.35–7.39 (m, 4H, ArH). 13C NMR (75.46 MHz, CDCl3):
= 119.8 (d,
J = 25.5 Hz, CH), 128.8 (CH), 129.1 (CH), 130.0 (CH), 131.1 (CH),
133.2 (C), 134.2 (C), 135.5 (C), 146.0 (C), 160.1 (d, J = 245.1 Hz, CF),
C), 133.6 (CH), 142.5 (d, J = 7.4 Hz, CH), 149.3 (C), 159.3 (d,
d
J = 247.0 Hz, CF). IR (ATR, cmꢀ1): V ¼ 3058 ðwÞ, 3014 (w), 2938 (w),
˜
d
2838 (w), 1723 (w), 1595 (w), 1563 (w), 1481 (m), 1439 (w), 1315
(w), 1280 (w), 1250 (m), 1197 (w), 1160 (m), 1104 (w), 1023 (m),
935 (w), 870 (w), 801 (m), 718 (w), 640 (w), 594 (w), 539 (w). GC–
MS (EI, 70 eV): m/z (%) = 314 (100) [M]+, 311 (16), 310 (99), 297
(18), 295 (19), 269 (16), 267 (18), 188 (65), 173 (11), 170 (14), 157
(15) 145 (18). HRMS (EI) calcd. for C18H15FO2S [M]+: 314.07768;
found 314.06859.
161.1 (C). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ115.0 (CF). IR (ATR,
cmꢀ1): V ¼ 2954 ðwÞ, 2919 (m), 2850 (m), 1737 (w), 1591 (w),
1555 (w), 1501 (w), 1473 (m), 1411 (w), 1302 (w), 1275 (w), 1213
(w), 1125 (w), 1088 (m), 1018 (m), 888 (m), 837 (m), 807 (s), 749
(m), 701 (w), 630 (m), 582 (m), 543 (w). MS (EI, 70 eV); m/z
(%) = 286 (100)(81Br) [M]+, 285 (10), 284 (77)(79Br), 170 (54), 169
(11). HRMS (EI) calcd. for C12H7BrClF [M]+: 283.93982; found
283.987663. HRMS (EI) calcd. for C12H781BrClF [M]+: 285.93687;
found 285.93759.
˜
7.2. 1-(40-Acetylphenyl)-4-(400-methoxyphenyl)-2-fluorobenzene
(9b):
Starting with
6
(200 mg, 0.79 mmol), Cs2CO3 (385 g,
1.81 mmol), Pd(PPh3)4 (3 mol%), 4-acetylyphenylboronic acid
(129 mg, 0.79 mmol) and 1,4-dioxane (4 mL) and 4-methoxyphe-
nylboronic acid (144 mg, 0.95 mmol), 9b was isolated as a colorless
solid (151 mg, 60%). Mp 89–90 8C. 1H NMR (300 MHz, CDCl3):
6.22. 1-Bromo-4(40-chlorophenyl)-2-fluorobenzene (8h):
Starting with
6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 4-chlorophenylboronic acid
(60 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8h was isolated as
a colorless solid (68 mg, 60%). Mp 94–95 8C. 1H NMR (300 MHz,
d
= 2.57 (s, 3H, CH3), 3.79 (s, 6H, OCH3), 6.91–6.94 (m, 2H, CH),
7.28–7.50 (m, 5H, CH), 7.61–7.65 (m, 2H, CH), 7.96–8.00 (m, 2H,
CH). 13C NMR (75 MHz, CDCl3):
= 26.7 (CH3), 55.4 (OCH3), 114.2,
d
CDCl3):
ArH), ꢀ7.41–7.49 (m, 4H, ArH), 7.50 (dd, J = 8.1, 1.2 Hz, 1H, ArH).
13C NMR (75.46 MHz, CDCl3):
= 108.3 (d, J = 20.9 Hz, C), 114.9 (d,
J = 23.1 Hz, CH), 123.7 (d, J = 3.3 Hz, CH), 128.2 (2CH), 129.2 (2CH),
133.9 (CH), 134.4 (C), 137.4 (C), 141.4 (d, J = 7.1 Hz, C), 159.4 (d,
d
= 7.19–7.24 (m, 1H, ArH), 7.31 (dd, J = 12.6, 1.8 Hz, 1H,
114.2 (CH), 114.3(d, J = 23.8 Hz, CH), 125.7(d, J = 3.2 Hz, CH),
127.1(d, J = 16.1 Hz, CH), 128.1 (2CH), 128.8 (2CH), 129.1 (2CH),
130.1 (C), 130.3 (C), 136.2 (C), 140.4, 140.9 (C), 159.8 (C), 160.3 (d,
d
1JCF = 249 Hz, C), 197.7 (CO). 19F NMR (282 MHz, CDCl3):
˜
d
= ꢀ113.40 (CF). IR (ATR, cmꢀ1): V ¼ 2956 ðwÞ, 2837 (w), 1675
JCF = 247.7 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ106.8 (CF). IR
(m), 1602 (m), 1578 (m), 1545 (m), 1484 (m), 1464 (m), 1393 (m),
1357 (m), 1300 (m), 1249 (m), 1173 (m), 1127 (m), 1023 (m), 1045
(w), 1023 (m), 809 (s), 693 (m), 577 (m), 3053 (w), (w). GC–MS (EI,
70 eV): m/z (%) = 320 (100) [M]+, 306 (16), 305 (72), 277 (6), 234
(10), 233 (23), 153 (11), 117 (3). HRMS (EI) calcd. for C21H17FO2
[M]+: 320.12063; found 320.12071.
(ATR, cmꢀ1): V ¼ 2954 ðwÞ, 2919 (m), 2850 (m), 1737 (w), 1591
(w), 1555 (w), 1501 (w), 1473 (m), 1411 (w), 1302 (w), 1275 (w),
1213 (w), 1125 (w), 1088 (m), 1018 (m), 888 (m), 837 (m), 807 (s),
749 (m), 701 (w), 630 (m), 582 (m), 543 (w). MS (EI, 70 eV): m/z
(%) = 286 (100) (81Br) [M]+, 284 (77)(79Br), 170 (54), 169 (11).
HRMS (EI) calcd. for C12H779BrClF [M]+: 283.93982; found
283.939663. HRMS (EI) calcd. for C12H781BrClF [M]+: 285.93687;
found 285.98759.
˜
7.3. 1-(30,50-Dimethylphenyl)-4-(phenyl)-2-fluorobenzene (9c):
Starting with
6 (200 mg, 0.79 mmol), Cs2CO3 (385 mg,
1.18 mmol), Pd(PPh3)4 (3 mol%), 3,5-di-methylphenylboronic acid
(118 mg, 0.79 mmol) and 1,4-dioxane (4 mL), and phenylboronic
acid (114 mg, 0.95 mmol) and 9c was isolated as a colorless solid
7. General procedure for the synthesis of 9a–f
The reaction was carried out in a pressure tube. To a dioxane
suspension (4 mL) of 6 (200 mg, 0.79 mmol), Pd(PPh3)4 (3 mol%)
and Ar1B(OH)2 (0.79 mmol) was added Cs2CO3 (385 mg,
1.18 mmol), and the resultant solution was degassed by bubbling
argon through the solution for 10 min. The mixture was heated at
90 8C under Argon atmosphere for 8 h. The mixture was cooled to
20 8C and Ar2B(OH)2 (0.95 mmol) and Cs2CO3 (385 mg, 1.18 mmol)
was added. The reaction mixtures were heated under Argon
atmosphere for 6 h at 100 8C. They were diluted with water and
extracted with CH2Cl2 (3 ꢁ 50 mL). The combined organic layers
were dried (Na2SO4), filtered and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatography (silica
gel, EtOAc/hexane = 1:4).
(141 mg, 65%). Mp 85–87 8C. 1H NMR (300 MHz, CDCl3):
d = 2.29 (s,
6H, CH3), 6.93 (s, 1H, ArH), 7.12–7.14 (m, 2H, ArH), 7.25–7.42 (m,
6H, ArH), 7.49–7.54 (m, 2H, ArH). 13C NMR (75 MHz, CDCl3):
d
= 21.4, 29.3 (CH3), 114.6 (d, J = 23.8 Hz, CH), 126.3 (d, J = 2.8 Hz,
CH), 126.9, (2CH), 127.7 (CH), 127.9 (CH), 128.5 (d, J = 1.4 Hz, CH),
128.9 (d, J = 3.48 Hz, CH), 129.4 (CH), 129.5 (d, J = 4.1 Hz, C), 130.8
(CH), 130.9 (d, J = 1.3 Hz, CH), 131.1 (C), 137.9, 138.5, 139.6 (C),
1
137.8, 142.4 (d, J = 16.9 Hz, C), 160.0 (d, JCF = 247.1 Hz, CF). 19F
˜
NMR (282 MHz, CDCl3):
d
= ꢀ117.7. IR (ATR, cmꢀ1): V ¼ 3052 ðwÞ,
3034 (w), 2915 (w), 2857 (w), 2732 (w), 1953 (w), 1892 (w), 1771
(w), 1747 (w), 1620 (m), 1601 (m), 1555 (m), 1475 (m), 1395 (m),
1328 (w), 1258 (m), 1183 (m), 1133 (m), 1037 (w), 1009 (w), 937
(m), 873 (m), 850 (m), 826 (s), 787 (m), 755 (s), 695 (s), 644 (m),
589 (m), 538 (m). GC–MS (EI, 70 eV): m/z (%) = 276 (100) [M]+.
HRMS (EI) calcd. for C20H17F [M]+: 276.13088; found 276.13058.
7.1. 1-(30,40-Dimethoxyphenyl)-4-(2-thienyl)-2-fluorobenzene (9a):
Starting with
6
(200 mg, 0.79 mmol), Cs2CO3 (385 g,
1.81 mmol), Pd(PPh3)4 (3 mol%), 3,4-dimethoxyyphenylboronic
acid (143 mg, 0.79 mmol) and 1,4-dioxane (4 mL) and 2-thienyl-
phenylboronic acid (121 mg, 0.95 mmol), 9a was isolated as a
colorless solid (131 mg, 53%). Mp 94–96 8C. 1H NMR (300 MHz,
8. General procedure for Suzuki–Miyaura reactions (synthesis
of 11a–j, 12a–c):
A 1,4-dioxane solution (4 mL per 0.3 mmol of 10) of 10, Cs2CO3,
Pd(PPh3)4 and arylboronic acid 2 was stirred at 90 8C for 6 or 8 h.
After cooling to room temperature, the organic and the aqueous
layers were separated and the latter was extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
CDCl3):
d
= 3.81 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.85–7.17 (m, 5H,
= 56.0
ArCH), 7.21–7.52 (m, 4H, ArH). 13C NMR (75 MHz, CDCl3):
d
(OCH3), 56.1 (OCH3), 107.2 (d, J = 20.0 CH), 110.0 (CH), 110.3 (CH),
111.5 (d, J = 4.5 Hz, CH), 113.6 (dd, J = 21.4, 7.1 Hz, J = 2.4 Hz, C),
114.7 (d, J = 22.6 Hz, CH), 119.4 (CH), 119.5 (C), 122.4 (t, J = 2.4 Hz,
C), 123.5 (d, J = 3.4 Hz, C), 128.5 (d, J = 13.2 Hz, C), 130.2 (d,
J = 9.5 Hz, C), 131.6 (t, J = 3.2 Hz, C), 131.9 (C), 132.3 (d, J = 11.1 Hz,

32
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
8.1. 1,3-Diphenyl-4-fluorobenzene (11a):
CDCl3):
ArH), 7.04–7.14 (m, 1H, ArH), 7.23–7.36 (m, 2H, ArH), 7.39–7.49
(m, 4H, ArH). 13C NMR (75 MHz, CDCl3):
= 55.3, (OCH3) 55.4
(OCH3), 114.0 (2CH), 114.1 (2CH), 114.3 (d, J = 23.7 Hz, CH), 116.4
(d, J = 23.3 Hz, CH), 126.6 (d, J = 8.57 Hz, CH), 127.7 (C), 128.1
(2CH), 128.9 (C), 130.2 (2CH), 132.8 (C), 137.3 (d, J = 3.52 Hz, C)
159.1 (d, J = 247.0 Hz, CF), 159.1 (d, J = 10.9 Hz, C). 19F NMR
d = 3.74, (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 6.84–6.92 (m, 4H,
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), phenylboronic acid (94 mg,
0.78 mmol) and 1,4-dioxane (4 mL), 11a was isolated as a colorless
d
oil (54 mg, 55%). 1H NMR (300 MHz, CDCl3):
d
= 7.09–7.16 (m, 1H,
ArH), 7.23–7.32 (m, 2H, ArH), 7.33–7.45 (m, 5H, ArH), 7.47–7.63
(m, 5H, ArH). 13C NMR (75 MHz, CDCl3):
= 116.3 (d, J = 23.6 Hz,
˜
d
(282 MHz, CDCl3):
d
= ꢀ119.9 (CF). IR (ATR, cmꢀ1): V ¼ 3037 ðwÞ,
CH), 127.1 (2CH), 127.6 (d, J = 8.02 Hz, CH), 128.6 (2CH), 128.9
(2CH), 129.1 (CH), 129.6 (CH), 130.9 (CH), 132.5 (C), 135.8 (C),
137.7 (d, J = 3.57 Hz, C), 140.2 (C), 159.4, (d, JCF = 249.0 Hz, CF). 19
3000 (w), 2955 (w), 2907 (w), 2836 (w), 1605 (m), 1571 (w), 1500
(w), 1480 (s), 1439 (m), 1383 (w), 1310 (w), 1247 (s), 1179 (s), 1114
(m), 1076 (m), 1016 (s), 1000 (m), 962 (w), 886 (w), 832 (s), 808 (s),
791 (s), 765 (w), 717 (w), 656 (w), 589 (w), 550 (m), 529 (m). MS
(EI, 70 eV): m/z (%) = 308 (100) [M]+, 293 (26), 265 (14). ESI-HRMS
calcd. for C20H17FO2 [M + H]+: 308.12071; found 308.12099.
F
NMR (282 MHz, CDCl3):
d
= ꢀ120.67 (CF). IR (ATR, cmꢀ1):
˜
V ¼ 3058 ðwÞ, 3029 (w), 2956 (w), 2927 (w), 2857 (w), 1948
(w), 1883 (w), 1806 (w), 1723 (m), 1600 (w), 1539 (w), 1478 (s),
1392 (w), 1332 (w), 1257 (m), 1183 (w), 1121 (m), 1073 (m), 1000
(w), 945 (w), 892 (m), 823 (s), 759 (s), 721 (m), 693 (s), 631 (s), 584
(s), 539 (m). MS (EI, 70 eV); m/z (%) = 248 (100) [M]+. HRMS (EI)
calcd. for C18H13OF [M]+: 248.09958; found 248.89357.
8.5. 1,3-Di(40-trifluoromethylphenyl-4-fluorobenzene (11e):
Starting with 10 (100 mg, 0.37 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-trifluoromethylphenylboronic
acid (148 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 11e was isolated
as a colorless solid (68 mg, 45%). Mp 148–150 8C. 1H NMR
8.2. 1,3-Di(40-methylphenyl)-4-fluorobenzene (11b):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(106 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 11b was isolated
as a colorless solid (67 mg, 62%). Mp 96–98 8C. 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
= 7.21 (dd, J = 18.6, 8.46 Hz, 1H, ArH), 7.49–
= 117.0 (d,
7.68 (m, 10H, ArH). 13C NMR (75 MHz, CDCl3):
d
J = 22.9 Hz, CH), 125.5 (dd, J = 7.85, 3.92 Hz, CH), 125.9 (dd, J = 7.71,
3.49 Hz, CH), 127.4 (2CH), 128.7 (d, J = 9.1 Hz, CH), 129.4 (d,
J = 3.34 Hz, CH), 129.6 (d, J = 3.49 Hz, CH), 136.5 (C), 139.0 (C),
143.3 (2C), 149.7 (C), 158.7 (d, JCF = 244.0 Hz, CF3), 159.2 (d,
JCF = 239.0 Hz, CF3), 159.9 (d, JCF = 252.0 Hz, CF). 19F NMR
CDCl3):
7.42 (m, 5H, CH), 7.51–7.58 (m, 1h, ArH). 13C NMR (75 MHz,
CDCl3): = 21.1, 21.3 (CH3), 116.3 (d, J = 23.3 Hz, CH), 127.1 (2CH),
d = 2.32 (CH3), 2.34 (CH3), 7.08–7.21 (m, 5H, ArH), 7.38–
d
127.1 (2CH), 127.1 (d, J = 8.0 Hz, CH), 128.9 (d, J = 8.0 Hz, CH), 129.1
(C), 129.3 (C), 129.6 (2CH), 129.6 (2CH), 132.9 (2C), 137.7 (2C),
160.9 (d, JCF = 248.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
(282 MHz, CDCl3):
d
= ꢀ62.5, ꢀ62.6 (CF3), ꢀ118.8 (CF). IR (ATR,
cmꢀ1): V ¼ 3052 ðwÞ, 3028 (w), 2959 (w), 2900 (w), 2864 (w), 1519
(w), 1484 (m), 1420 (w), 1380 (w), 1319 (w), 1269 (m), 1212 (m),
1045 (w), 1007 (w), 964 (w), 896 (w), 831 (m), 813 (m), 759 (w),
722 (w), 676 (w), 615 (w), 563 (m), 536 (w). MS (EI, 70 eV): m/z
(%) = 384 (100) [M]+. ESI-HRMS calcd. for C20H11F7 [M + H]+:
384.07435; found 384.07470.
˜
˜
d
= ꢀ120.72 (CF). V ¼ 3052 ðwÞ, 2975 (w), 2916 (w), 2848 (w),
2734 (w), 1899 (w), 1797 (w), 1731 (w), 1645 (w), 1590 (w), 1515
(w), 1483 (m), 1450 (w), 1381 (w), 1280 (w), 1249 (w), 1214 (w),
1126 (w), 1039 (w), 960 (w), 902 (w), 834 (w), 809 (s), 719 (m), 663
(w), 615 (w), 549 (m). IR (ATR, cmꢀ1): GC–MS (EI, 70 eV); m/z
(%) = 276 (100) [M]+. HRMS (EI) calcd. for C20H17F [M]+: 276.13088;
found 276.13062.
8.6. 1-(30-Methylphenyl)-3-(30-methylphenyl)-4-fluorobenzene
(11f):
8.3. 1,3-Di(20-methoxyphenyl)-4-fluorobenzene (11c):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 3-methylphenylboronic acid
(116 mg, 0.85 mmol) and 1,4-dioxane (4 mL), 11f was isolated
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 2-methoxyphenylboronic acid
(94 mg, 78 mmol) and 1,4-dioxane (4 mL), 11c was isolated as a
colorless solid (73 mg, 60%). Mp 99–100 8C. 1H NMR (300 MHz,
as a colorless oil (83 mg, 57%). 1H NMR (300 MHz, CDCl3):
d = 2.49
(s, 6H, CH3), 7.23–7.31 (m, 3H, ArH), 7.37–7.48 (m, 6H, ArH), 7.54–
7.60 (m, 1H, ArH), 7.69 (q, J = 7.5 Hz, 2.5 Hz, 1H, ArH). 13C NMR
CDCl3):
7.11 (m, 1H, ArH), 7.17–7.25 (m, 3H, ArH), 7.39–7.48 (m, 2H, ArH).
13C NMR (75 MHz, CDCl3):
= 55.6, 55.7 (OCH3), 111.1 (CH), 111.2
(CH), 114.9 (d, J = 22.5 Hz, CH), 120.5 (CH), 120.9 (CH), 128.7 (2C),
125.7 (d, J = 15.8 Hz, C), 130.1 (d, J = 8.3 Hz, CH), 130.9 (2CH), 131.5
(2CH), 133.0 (d, J = 8.3 Hz, CH), 134.1 (d, J = 3.8 Hz, C), 157.1, 157.6
(C), 159.1 (d, J = 244.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= 3.75, 3.75 (s, 3H, OCH3), 6.89–6.98 (m, 4H, ArH), 7.04–
(75 MHz, CDCl3): d = 21.6 (2CH3), 116.2 (CH), 116.5 (CH), 124.2
(CH), 126.2 (d, JCF = 3.0 Hz), 127.5 (d, J = 8.4 Hz, CH), 127.9 (CH),
128.1 (CH), 128.4 (CH), 128.5 (CH), 128.8 (CH), 129.6 (d, J = 3.8 Hz,
CH), 129.8 (d, J = 2.2 Hz, CH), 129.3 (C), 129.5 (C), 135.8 (C), 137.7
(d, J = 4.7 Hz, C), 138.1 (C), 138.5 (C), 140.2 (C), 159.4 (d,
d
JCF = 248.6.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ120.3 (CF).
IR (ATR, cmꢀ1): V ¼ 3031 ðwÞ, 2947 (w), 2919 (w), 2860 (w), 2732
(w), 1605 (w), 1584 (w), 1504 (w), 1475 (s), 1379 (w), 1257 (w),
1220 (m), 1171 (w), 1123 (w), 1094 (w), 1046 (w), 999 (w), 881
(m), 823 (m), 781 (s), 720 (m), 698 (s), 633 (w), 562 (w), 523 (w),
441 (m). MS (EI, 70 eV): m/z (%) = 276 (100) [M]+. HRMS (EI) calcd.
for C20H17F [M]+: 276.13088; found 276.13098.
˜
˜
d
= ꢀ116.36 (CF). IR (ATR, cmꢀ1): V ¼ 3053 ðwÞ, 2959 (m), 2924
(m), 2852 (m), 2836 (m), 1577 (m), 1494 (s), 1455 (s), 1434 (m),
1390 (m), 1256 (m), 1228 (m), 1109 (m), 1022 (s), 825 (m), 792 (m),
825 (s), 792 (s), 748 (s), 625 (m), 597 (m), 544 (m). GC–MS (EI,
70 eV); m/z (%) = 308 (100) [M]+, 278 (13), 260 (6), 233 (10), 110
(3). HRMS (EI) calcd. for C20H17O2F[M]+: 308.12071; found
308.12018.
8.7. 1,3-Di(2-thienyl)-4-fluorobenzene (11g):
8.4. 1,3-Di(40-methoxyphenyl)-4-fluorobenzene (11d):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (190 mg,
0.50 mmol), Pd(PPh3)4 (3 mol%), 2-thienylboronic acid (49 mg,
0.39 mmol) and 1,4-dioxane (4 mL), 11g was isolated as a colorless
solid (49 mg, 48%). Mp 91–93 8C. 1H NMR (300 MHz, CDCl3):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(85 mg, 70 mmol) and 1,4-dioxane (4 mL), 11d was isolated as a
colorless solid (94 mg, 70%). Mp 101–103 8C. 1H NMR (300 MHz,
d
= 7.00–7.06 (m, 2H, ArH), 7.22–7.34 (m, 5H, ArH), 7.41–7.43 (m,
1H, ArH), 7.52–7.57 (m, 1H, ArH). 13C NMR (75.46 MHz, CDCl3):

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
33
d
= 113.4 (d, J = 24.5 Hz, CH), 121.1 (d, J = 13.5 Hz, C), 121.8 (d,
(300 MHz, CDCl3):
d
= 3.68 (s, 3H, CH3), 3.69 (s, 3H, OCH3), 3.71
J = 3.1 Hz, CH), 123.8 (CH), 125.6 (CH), 125.8 (d, J = 4.5 Hz, CH),
126.3 (d, J = 7.1 Hz, CH), 127.8 (CH), 128.3 (CH), 129.0 (d, J = 4.2 Hz,
CH), 134.9 (d, J = 9.4 Hz, C), 136.9 (d, J = 3.87 Hz, C), 142.6 (d,
(s, 6H, OCH3), 6.70–6.80 (m, 6H, ArH), 7.04–7.10 (m, 1H, ArH),
7.40–7.45 (m, 2H, ArH). 13C NMR (75 MHz, CDCl3):
= 55.8
(2OCH3), 56.3 (OCH3), 56.4 (OCH3), 112.4 (CH), 112.6 (CH),
113.2 (CH), 114.2 (CH), 115.1 (d, J = 22.6 Hz, CH), 116.7 (CH),
117.1 (CH), 125.6 (d, J = 16.4 Hz, C), 126.0 (C), 130.3 (d, J = 7.6 Hz,
CH), 130.5 (C), 132.8 (d, J = 4.0 Hz, CH), 134.0 (d, J = 3.5 Hz, C), 150.7
d
J = 2.9 Hz, C), 159.2 (d, JCF = 250.2 Hz, CF). 19F NMR (282.4 MHz,
˜
CDCl3):
d
= ꢀ107.4 (CF). IR (ATR, cmꢀ1): V ¼ 3102 ðwÞ, 3067 (w),
2956 (w), 2871 (w), 1886 (w), 1799 (w), 1724 (w), 1605 (w), 1555
(w), 1484 (w), 1421 (w), 1355 (w), 1289 (w), 1244 (w), 1177 (w),
1121 (w), 1071 (w), 999 (w), 960 (w), 866 (w), 841 (w), 808 (m),
746 (w), 696 (m), 613 (w), 561 (w), 529 (w). GC–MS (EI, 70 eV); m/z
(%) = 260 (100) [M]+, 215 (13). HRMS (EI) calcd. for C14H9FS2 [M]+:
260.01242; found 260.01360.
(C), 151.3 (C), 153.5 (C), 153.8 (C), 159.3 (d, JCF = 249.0 Hz, CF). 19
F
NMR (282 MHz, CDCl3):
d
= ꢀ116.3 (CF). IR (ATR, cmꢀ1):
˜
V ¼ 3428 ðwÞ, 3021 (w), 2948 (w), 2832 (w), 1582 (w), 1486 (s),
1463 (m), 1407 (m), 1381 (m), 1295 (m), 1264 (m), 1220 (s), 1174
(s), 1113 (m), 1049 (s), 1023 (s), 915 (w), 855 (m), 803 (m), 755 (w),
706 (s), 5651 (w), 568 (w), 507 (w), 468 (w) cmꢀ1. MS (EI, 70 eV):
m/z (%) = 368 (100) [M]+, 339 (12), 338 (57), 169 (12). HRMS (ESI)
calcd. for C22H22O4F [M + H]+: 369.14966; found 369.14871.
8.8. 1,3-Di(20,30-dimethoxyphenyl)-4-fluorobenzene (11h):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (263 mg,
0.81 mmol), Pd(PPh3)4 (3 mol%), 2,3-dimethoxyphenylboronic
acid (141 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 11h was
isolated as a colorless solid (84 mg, 58%). Mp 176–178 8C. 1H
8.11. 3-Bromo-4(40-methyl)-4-fluorobiphenyl (12a):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (126 mg,
0.39 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(53 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 12a was isolated as
a colorless solid (65 mg, 63%). Mp 99–101 8C. 1H NMR (300 MHz,
NMR (300 MHz, CDCl3):
d = 3.59 (s, 3H, OCH3), 3.75 (s, 3H, OCH3),
3.81 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 6.76–6.87 (m, 4H, ArH), 7.01–
7.07 (m, 2H, ArH), 7.28–7.32 (m, 3H, ArH). 13C NMR (75.46 MHz,
CDCl3):
d
= 55.8 (OCH3), 55.9 (OCH3), 60.6 (OCH3), 60.7 (OCH3),
CDCl3): d = 2.33 (s, 3H, CH3), 6.93–6.98 (m, 1H, ArH), 7.17–7.20 (m,
111.6 (CH), 112.1 (d, J = 32.6 Hz, CH), 116.3 (d, J = 25.2 Hz, CH),
122.4 (CH), 123.3 (d, J = 1.3 Hz, CH), 123.9 (d, J = 36.6 Hz, CH), 124.5
(CH), 124.6 (d, J = 3.6 Hz, C), 130.1 (CH), 131.4 (d, J = 3.8 Hz, C),
134.4 (d, J = 1.8 Hz, C), 139.4 (d, J = 8.2 Hz, C), 146.9 (d, J = 36.8 Hz,
2H, ArH), 7.29–7.36 (m, 2H, ArH), 7.46–7.49 (dd, J = 6.87, 2.60 Hz,
1H, ArH), 7.38 (d, J = 1.5 Hz, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
= 21.3 (OCH3), 108.9 (d, J = 21.0 Hz, C), 114.1 (2CH), 117.8 (d,
J = 18.0 Hz, CH), 130.1, 130.2 (CH), 131.0 (C), 131.1 (C), 132.2 (C),
136.1 (C), 159.7 (C), 165.8 (d, J = 248.0 Hz, CF). 19F NMR (282 MHz,
C), 152.8 (C), 153.1 (d, J = 21.2 Hz, C), 159.6 (d, J = 246.6 Hz, CF). 19
F
= ꢀ114.7 (CF). IR (ATR, cmꢀ1):
CDCl3):
d
= ꢀ119.8 (CF). IR (ATR, cmꢀ1): V ¼ 3029 ðwÞ, 2918 (w),
˜
NMR (282.4 MHz, CDCl3):
d
˜
V ¼ 3103 ðwÞ, 3058 (w), 3006 (w), 2962 (w), 2930 (w), 2837
(w), 1621 (w), 1598 (w), 1579 (w), 1556 (w), 1515 (w), 1478 (w),
1441 (w), 1402 (m), 1316 (w), 1264 (m), 1208 (w), 1188 (w), 1113
(m), 1084 (w), 1032 (m), 998 (m), 934 (w), 875 (w), 831 (w), 787
(m), 751 (m), 651 (w), 600 (w), 535 (m). MS (MS, 70 eV): m/z
(%) = 368 (100) [M]+, 338 (38). HRMS (EI) calcd. for C22H21O4F [M]+:
368.14184; found 368.12118.
2853 (w), 2733 (w), 1914 (w), 1755 (w), 1725 (w), 1596 (w), 1519
(w),1468 (w), 1378 (w), 1288 (w), 1265 (m), 1131 (w), 1074 (w),
1014 (s), 949 (w), 881 (w), 806 (s), 717 (w), 695 (m), 656 (w), 591
(w), 531 (w). GC–MS (EI, 70 eV): m/z (%) = 264 (100)(79Br) [M]+, 185
(15), 184 (19), 183 (52), 170 (21), 165 (42). HRMS (EI) calcd. for
13H10BrF [M]+: 263.99444; found 263.994477 and calcd. for
13H1081BrF [M]+: 265.99240; found 265.99252.
C
C
8.9. 1-(40-Ethylphenyl)-3-(40-ethylphenyl)-4-fluorobenzene (11i):
8.12. 3-Bromo-1-(40-methoxy)-4-fluorobiphenyl (12b):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-ethylphenylboronic acid
(128 mg, 0.85 mmol) and 1,4-dioxane (4 mL), 11i was isolated
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (126 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(59 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 12b was isolated as a
colorless solid (78 mg, 70%). Mp 66–68 8C. 1H NMR (300 MHz,
as a colorless oil (69 mg, 57%). 1H NMR (300 MHz, CDCl3):
d = 1.27
(t, J = 7.5 Hz, 3H, CH3), 1.28 (t, J = 7.5 Hz, 3H, CH3), 2.65–2.74 (m,
4H, CH2), 7.18 (q, J = 10.4 Hz, 8.5 Hz, 1H, ArH), 7.28 (t, J = 8.1 Hz, 4H,
ArH), 7.45–7.53 (m, 5H, ArH), 7.62 (q, J = 7.7 Hz, 2.7 Hz, 1H, ArH).
CDCl3):
J = 6.6 Hz, 1H, CH), 7.18–7.20 (m, 2H, CH), 7.34 (d, J = 1.5 Hz, 1H,
CH), 7.38 (d, J = 1.5 Hz, 1H, CH). 13C NMR (75 MHz, CDCl3):
= 55.4
d = 3.78 (s, 3H, OCH3), 6.89–6.96 (m, 2H, ArH), 6.96 (d,
d
13C NMR (75 MHz, CDCl3):
d
= 15.5 (CH3), 15.6 (CH3), 28.5 (CH2),
(OCH3), 108.9 (d, J = 21.0 Hz, C), 114.1 (2CH), 117.8 (d, J = 18.0 Hz,
28.6 (CH2), 159.3 (d, JCF = 247.4 Hz, CF), 143.7 (d, JCF = 32.4 Hz, C),
137.6 (C), 137.5 (d, J = 3.6 Hz, C), 133.1 (CH), 129.3 (d, J = 3.8 Hz,
CH), 129.0 (d, J = 3.0 Hz, CH), 128.3 (2CH), 128.0 (2CH), 128.2 (dd,
CH), 130.1, 130.2 (CH), 131.0 (CH), 131.1 (CH), 132.2 (C), 136.1 (C),
159.7 (C), 165.8 (d, J = 248.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
˜
d
= ꢀ119.8 (CF). IR (ATR, cmꢀ1): V ¼ 3074 ðmÞ, 3015 (m), 2960 (m),
JCF = 166.0 Hz, C), 127.0 (CH), 116.4 (d, JCF = 22.0 Hz, C). 19F NMR
2837 (w), 1605 (m), 1514 (m), 1295 (m), 1255 (s), 1075 (s), 1016
(s), 875 (m), 792 (m), 696 (m), 624 (m), 576 (s). GC–MS (EI, 70 eV);
m/z (%) = 280 (100) (79Br) [M]+, 267 (24), 265 (18), 239 (34), 237
(30), 213 (11), 170 (11), 158 (24), 157 (51), 138 (9), 44 (11). HRMS
(EI) calcd. for C13H10OBrF [M]+: 279.98936; found 279.989522 and
calcd. for C13H10O81BrF [M]+: 281.98731; found 281.98738.
˜
(282 MHz, CDCl3):
d
= ꢀ120.7 (CF). IR (ATR, cmꢀ1): V ¼ 3024 ðwÞ,
2963 (m), 2929 (w), 2871 (w), 1516 (w), 1484 (s), 1456 (w), 1412
(w), 1384 (w), 1258 (w), 1217 (m), 1118 (w), 1044 (w), 965 (w),
898 (w), 831 (m), 815 (s), 703 (w), 659 (w), 616 (w), 562 (w), 500
(w) cmꢀ1. MS (EI, 70 eV): m/z (%) = 304 (100) [M]+, 290 (21), 289
(91), 274 (14), 137 (16). HRMS (EI) calcd. for C22H21F [M]+:
304.16218; found 304.16244.
8.13. 3-Bromo-4(40-ethyl)-4-fluorobiphenyl (12c):
8.10. 1-(20,50-Dimethoxyphenyl)-3-(20,50-dimethoxyphenyl)-4-
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (126 mg,
0.39 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(53 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 12c was isolated as
a colorless solid (65 mg, 63%). Mp 99–101 8C. 1H NMR (300 MHz,
d = 7.76 (dd, J = 6.6 Hz, 2.3 Hz,
1H, ArH), 7.48 (ddd, J = 8.5 Hz, 4.6 Hz, 2.3 Hz, 1H, ArH), 7.45
(d, J = 8.5 Hz, 2H, ArH), 7.28 (d, J = 8.5, 1H, ArH), 7.18 (t, J = 8.5 Hz,
fluorobenzene (11j):
Starting with 10 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 2,5-dimethoxyphenylboronic
acid (158 mg, 0.85 mmol) and 1,4-dioxane (4 mL), 11j was isolated
as a colorless solid (91 mg, 65%). Mp 149–150 8C. 1H NMR
CDCl3): 1H NMR (300 MHz, CDCl3):

34
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
= ꢀ115.7 (CF). IR (ATR, cmꢀ1): V ¼ 3060 ðwÞ, 2998 (w),
˜
1H, ArH), 2.71 (q, J = 7.6 Hz, 2H, CH2), 1.29 (t, J = 7.6 Hz, 3H, CH3).
13C NMR (75 MHz, CDCl3):
= 138.83 (d, J = 3.8 Hz, CH), 131.8 (C),
109.2 (d, J = 21.1 Hz, CH), 158.4 (d, JF = 247.2 Hz, CF), 116.5 (d,
J = 22 Hz, CH), 127.3 (d, J = 7.1 Hz, CH), 136.2 (C), 126.9 (C), 128.4
(C), 144.0 (C), 28.4 (C), 15.5 (C). 19F NMR (282 MHz, CDCl3):
CDCl3):
d
d
2929 (w), 2833 (w), 2052 (w), 1898 (w), 1724 (w), 1597 (w), 1494
(m), 1456 (m), 1403 (w), 1363 (w), 1274 (m), 1245 (s), 1175 (m),
1120 (m), 1052 (m), 1052 (m), 1024 (m), 967 (w), 889 (w), 820 (w),
788 (w), 747 (s), 694 (w), 627 (w), 560 (w), 536 (m). MS (GC,
70 eV): m/z (%) = 248 (100) [M]+, 247 (39), 246 (20), 244 (15), 233
(35), 227 (22), 226 (21), 220 (11) cmꢀ1. HRMS (EI): calcd. for
˜
d
= ꢀ110.3 (CF). IR (ATR, cmꢀ1): V ¼ 3024 ðwÞ, 2964 (w), 2929 (w),
2871 (w), 1903 (w), 1598 (w), 1487 (s), 1377 (w), 1264 (m), 1129
(w), 1045 (m), 964 (w), 835 (w), 812 (s), 779 (w), 691 (m), 624 (w),
555 (m). MS (EI, 70 eV); m/z (%) = 278 (64) [M]+, 266 (13), 265 (97),
264 (14), 263 (100), 184 (17), 183 (65), 170 (22). HRMS (EI) calcd.
for C14H12Br F [M]+: 278.01009; found 278.009637, C14H1281BrF
calcd. 280.00805; found 280.00771.
C
18H13F [M]+ 248.09946, found 248.09958.
9.3. 1,2-Di(40-methylphenyl)-4-fluorobenzene (15b):
Starting with 14 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-methylphenylboronic acid
(106 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 15b was isolated
as a colorless solid (89 mg, 81%). Mp 96–98 8C. 1H NMR (300 MHz,
9. Procedure for the synthesis of 13
The reaction was carried out in a pressure tube. To a dioxane
suspension (4 mL) of 10 (200 mg, 0.79 mmol), Pd(PPh3)4 (3 mol%)
and Ar1B(OH)2 (0.79 mmol) was added Cs2CO3 (385 mg,
1.18 mmol), and the resultant solution was degassed by bubbling
argon through the solution for 10 min. The mixture was heated at
90 8C under Argon atmosphere for 8 h. The mixture was cooled to
20 8C and Ar2B(OH)2 (0.95 mmol) and Cs2CO3 (385 mg, 1.18 mmol)
was added. The reaction mixtures were heated under Argon
atmosphere for 6 h at 100 8C. They were diluted with water and
extracted with CH2Cl2 (3 ꢁ 50 mL). The combined organic layers
were dried (Na2SO4), filtered and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatography (silica
gel, EtOAc/hexane = 1:4).
CDCl3):
ArH), 7.45–7.49 (m, 4H, ArH), 7.60 (q, J = 7.4, 2.2 Hz, 1H, ArH). 13
NMR (75 MHz, CDCl3): = 20.4 (CH3), 20.6 (CH3), 115.6 (d,
J = 24.7 Hz, 2CH), 126.2 (2CH), 126.5 (d, J = 8.3 Hz, CH), 128.3 (d,
J = 2.6 Hz, CH), 128.6 (2CH), 128.6 (2CH), 128.9 (2CH), 132.3 (C),
136.5 (C), 136.8 (d, J = 15.4 Hz, C), 136.9 (d, J = 3.9 Hz, C), 158.5 (d,
d = 2.39 (s, 3H, CH3), 2.40 (s, 3H, CH3), 7.14–7.27 (m, 6H,
C
d
JCF = 248.0 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ121.1 (CF). IR
(ATR, cmꢀ1): V ¼ 3051 ðwÞ, 2946 (w), 2853 (w), 2733 (w), 1898 (w),
1731 (w), 1645 (w), 1589 (w), 1514 (w), 1483 (m), 1407 (w), 1380
(w), 1308 (w), 1249 (w), 1207 (w), 1116 (w), 1039 (w), 1009 (w),
959 (w), 902 (w), 856 (w), 808 (m), 764 (w), 719 (w), 663 (w), 615
(w), 549 (w) cmꢀ1. MS (GC, 70 eV): m/z (%) = 277 (21), 276 (100)
[M]+. HRMS (EI): calcd. for C20H17F[M]+ 276.13088, found
276.13093.
˜
9.1. 1-(40-Trifluoromethylphenyl)-3-(40-methylphenyl)-4-
fluorobenzene (13):
9.4. 1,2-Di(20-methoxyphenyl)-4-fluorobenzene (15c):
Starting with 10 (200 mg, 0.78 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-trifluoromethylphenylboronic
acid (148 mg, 0.78 mmol) and 4-methoxyphenylboronic acid
(142 mg, 0.93 mmol) and 1,4-dioxane (4 mL), 13 was isolated as a
colorless solid (79 mg, 58%). Mp 149–151 8C. 1H NMR (300 MHz,
Starting with 14 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 2-methoxyphenylboronic acid
(118 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 15c was isolated as
a colorless solid (83 mg, 67%). Mp 101–103 8C. 1H NMR (300 MHz,
CDCl3): d = 3.47 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.70 (t, J = 7.2 Hz,
CDCl3):
1H, ArH), 7.26–7.45 (m, 2H, ArH), 7.60–7.65 (m, 4H, ArH). 13C NMR
(75 MHz, CDCl3): = 55.4 (OCH3), 110.3 (CH), 110.4 (CH), 111.3
d
= 3.73 (s, OCH3), 6.86–6.95 (m, 4H, ArH), 7.05–7.16 (m,
1H, ArH), 6.78–6.83 (m, 1H, ArH), 6.96–7.04 (m, 4H, ArH), 7.08–
7.17 (m, 3H, ArH), 7.24–7.26 (m, 1H, ArH), 7.30–7.36 (m, 1H, ArH).
13C NMR (75 MHz, CDCl3):
d = 53.8 (OCH3), 54.6 (OCH3), 109.2 (d,
d
(CH), 114.1 (CH), 114.4 (CH), 116.6 (d, J = 22.8 Hz, CH), 125.4 (d,
J = 24.5 Hz, CH), 126.7 (C), 127.1 (CH), 127.4 (CH), 128.1 (t,
J = 3.87 Hz, CH), 129.4 (CH), 130.2 (CH), 132.4 (C), 155.4 (C), 157.9
(d, J = 13.3 Hz, C), 158.2 (d, JCF = 247.8 Hz, CF), 159.4 (d,
J = 11.2.0 Hz, C), 160.0 (d, J = 9.6 Hz, C). 19F NMR (282 MHz,
J = 3.1 Hz, CH), 110.0 (CH), 112.8 (d, J = 20.1 Hz, CH), 116.2 (d,
J = 20.1 Hz, CH), 119.0 (d, J = 30.8 Hz, CH), 126.7 (CH), 127.2 (d,
J = 17.7 Hz, CH), 127.5 (CH), 128.3 (CH), 128.7 (d, J = 2.1 Hz, C),
128.9 (CH) 130.2 (d, J = 18.2 Hz, C), 130.9 (d, J = 8.4 Hz, CH), 139.2
(d, J = 9.1 Hz, C), 155.5 (d, J = 60.0 Hz, C), 155.1 (C), 160.8 (d,
CDCl3):
d
= ꢀ61.9, –(CF3), ꢀ110.7 (CF). IR (ATR, cmꢀ1):
JCF = 245.7 Hz, CF). 19F NMR (282 MHz, CDCl3):
d
= ꢀ116.4 (CF). IR
V ¼ 3072 ðwÞ, 3037 (w), 2957 (w), 2912 (w), 2837 (w), 1605
(m), 1569 (m), 1517 (m), 1486 (s), 1439 (s), 1384 (m), 1323 (s),
1273 (s), 1234 (s), 1177 (s), 1124 (s), 1069 (s), 1012 (s), 962 (w),
891 (w), 835 (m), 809 (s), 794 (m), 765 (m), 714 (w), 656 (w), 598
(w), 550 (m), 530 (m). MS (EI, 70 eV): m/z (%) = 346 (100) [M]+, 331
(11). HRMS (EI) calcd. for C20H14OF4 [M]+: 346.09753; found
346.09689.
(ATR, cmꢀ1): V ¼ 3058 ðwÞ, 2960 (w), 2833 (w), 1894 (w), 1724
(w), 1597 (w), 1498 (w), 1454 (w), 1404 (w), 1298 (w), 1252 (w),
1173 (w), 1120 (w), 1052 (w), 1021 (w), 934 (w), 884 (w), 821 (w),
797 (w), 747 (w), 694 (w), 612 (w), 559 (w), 536 (w). MS (GC,
70 eV): m/z (%) = 308 (100) [M]+, 277 (20), 262 (10), 245 (10), 233
(21) cmꢀ1. HRMS (EI): calcd. for C20H17O2F [M]+ 308.12071, found
308.12087.
˜
˜
9.2. 1,2-Diphenyl-4-fluorobenzene (15a):
9.5. 1,2-Di(40-methoxyphenyl)-4-fluorobenzene (15d):
Starting with 14 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), phenylboronic acid (95 mg,
0.78 mmol) and 1,4-dioxane (4 mL), 15a was isolated as a
Starting with 14 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid
(118 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 15d was isolated as a
dark brownsolid (94 mg, 70%). Mp 86–88 8C: 1H NMR (300 MHz,
colorless oil (79 mg, 79%). 1H NMR (300 MHz, CDCl3):
d
= 7.08–
7.12 (m, 6H, ArH), 7.18–7.21 (m, 6H, ArH), 7.35–7.43 (m, 1H, ArH).
13C NMR (75 MHz, CDCl3):
= 114.1 (d, J = 21.0 Hz, CH), 117.1 (d,
CDCl3):
d = 3.70 (s, 3H, OCH3), 3.76(s, 3H, OCH3), 6.68 (dd, J = 8.7,
d
2.1 Hz, 3H, ArH), 6.86–7.02 (m, 6H,ArH), 7.24 (dd, J = 8.4, 5.6 Hz,
1H, ArH), 7.40 (dt, J = 6.8, 2.6 Hz, 1H, ArH). 13C NMR (75.4 MHz,
CDCl3): d = 55.1 (OCH3), 55.3 (OCH3), 113.4 (J = 2.8 Hz, 2CH), 113.7
(d, J = 20.9 Hz, CH), 114.1 (CH), 116.9 (d, J = 20.9 Hz, CH), 127.7
(CH), 130.8 (d, J = 8.1 Hz, 2CH), 131.9 (d, J = 8.7 Hz, CH), 133.0
J = 21.0 Hz, CH), 126.5 (CH), 126.9 (CH), 127.0 (d, J = 52.8 Hz, C),
127.9 (d, J = 4.1 Hz, CH), 129.7 (d, J = 12.0 Hz, CH), 132.1 (d,
J = 8.2 Hz, CH), 136.6 (d, J = 3.2 Hz, C), 140.4 (d, J = 2.0 Hz, C), 142.4
(d, J = 7.9 Hz, C), 162.0 (d, JCF = 246.7 Hz, CF). 19F NMR (282 MHz,

M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
35
´
(d, J = 2.5 Hz, C), 133.3 (d, J = 18.9, C), 136.9 (d, J = 2.5 Hz, C), 141.9
(d, J = 7.4 Hz, C), 158.4 (d, J = 18.4 Hz, C), 158.7 (C), 161.7
TAMOP-4.2.1/B-09/KONV-2010-007 project. The project is imple-
mented through the New Hungary Development Plan, co-financed
by the European Social Fund and the European Regional Develop-
ment Fund.
(d, JCF = 247.1 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ115.8
(CF). IR (ATR, cmꢀ1): V ¼ 3072 ðwÞ, 3012 (w), 2956 (w), 2929 (w),
2838 (w), 2535 (w), 2065 (w), 2032 (w),1892 (w), 1766 (w), 1605
(m), 1567 (w), 1717 (w), 1464 (m), 1399 (w), 1328 (w), 1289 (m),
1239 (s), 1175 (m), 1115 (m), 1079 (m), 1014 (m), 967 (w), 885 (m),
820 (s), 781 (m), 746 (w), 700 (w), 645 (w), 604 (w), 564 (m), 545
(m) cmꢀ1. MS (GC, 70 eV): m/z (%) = 308 (100) [M]+, 233 (20), 221
(11), 220 (13). HRMS (EI): calcd. for C20H17O2F [M]+ 308.12071,
found 308.12056.
˜
References
[1] (a) R. Filler, Y. Kobayasi, L.M. Yagupolskii (Eds.), Fluorine in Bioorganic Chemistry,
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(d) P. Kirsch, Modern Fluoroorganic Chemistry, VCH, Weinheim, 2004;
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9.6. 1,2-Di(40-vinylphenyl)-4-fluorobenzene (15e):
(f) T. Ryckmanns, L. Balancon, O. Berton, C. Genicot, Y. Lamberty, B. Lallemand, P.
Passau, N. Pirlot, L. Que´re´, P. Talaga, Bioorg. Med. Chem. Lett. 12 (2002) 261–264;
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1310;
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(j) S. Purser, P.R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 37 (2008)
320–330;
Starting with 14 (100 mg, 0.39 mmol), Cs2CO3 (253 mg,
0.78 mmol), Pd(PPh3)4 (3 mol%), 4-vinylphenylboronic acid
(115 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 15e was isolated
as a colorless solid (53 mg, 45%). Mp. 170–172 8C. 1H NMR
(300 MHz, CDCl3):
Hz, 2H, CH2), 6.77 (q, J = 17.4, 10.8 Hz, 2H, CH), 7.38–7.60 (m, 11H,
ArH). 13C NMR (75.46 MHz, CDCl3):
= 114.3 (2CH2), 114.4 (CH2),
d = 5.30 (d, J = 10.9 Hz, 2H, CH2), 5.81 (d, J = 15.4,
d
(k) S.M. Ametamey, M. Honer, P.A. Schubiger, Chem. Rev. 108 (2008) 1501–1516.
[2] (a) H.A. Albrecht, G. Beskid, N.H. Georgopapadakou, D.D. Keith, F.M. Konzelmann,
D.L. Pruess, P.L. Rossman, C.C. Wei, J.G. Christenson, J. Med. Chem. 34 (1991)
2857–2864;
114.6 (CH), 122.7 (d, J = 3.0 Hz, CH), 126.4 (CH), 126.8 (CH), 127.0
(CH), 127.4 (d, J = 13.8 Hz, C), 129.0 (d, J = 3.6 Hz, CH), 130.8 (d,
J = 4.4 Hz, CH), 134.8 (d, J = 2.2 Hz, CH), 136.3 (d, J = 11.0 Hz, CH),
137.1 (d, J = 18.2 Hz, C), 138.7 (d, J = 2.4 Hz, C), 141.8 (d, J = 8.0 Hz,
C), 160.0 (d, JCF = 247.6 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
(b) H.A. Albrecht, G. Beskid, J.G. Christenson, K.H. Deitcher, N.H. Georgopapada-
kou, D.D. Keith, F.M. Konzelmann, D.L. Pruess, C.C. Wie, J. Med. Chem. 37 (1994)
400–407;
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(e) S. Anjaiah, S. Chandrasekhar, R. Gree, Adv. Synth. Catal. 346 (2004) 1329–
1334;
ꢀ117.4 (CF). IR (ATR, cmꢀ1): V ¼ 3087 ðmÞ, 3035 (m), 2956 (m),
˜
2920 (m), 2850 (m), 1919 (w), 1834 (w), 1651 (w), 1627 (m), 1572
(m), 1484 (m), 1431 (m), 1393 (m), 1359 (m), 1296 (m), 1258 (m),
1184 (m), 1137 (m), 1046 (w), 992 (m), 912 (m), 851 (m), 816 (s),
750 (m), 699 (m), 577 (m), 536 (m) cmꢀ1. MS (GC, 70 eV): m/z
(%) = 300 (100) [M]+. HRMS (EI): calcd. for C22H17F[M]+ 300.13088,
found 300.13127.
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0.78 mmol), Pd(PPh3)4 (3 mol%), 2,3-dimethoxyphenylboronic
acid (141 mg, 0.78 mmol) and 1,4-dioxane (4 mL), 15f was isolated
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(300 MHz, CDCl3):
d = 3.59 (s, 3H, OCH3), 3.64 (s, 3H, OCH3),
3.80 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 6.58 (dt, J = 9.5, 2.0 Hz, 1H,
ArH), 6.72–6.94 (m, 5H, ArH), 7.04–7.18 (m, 2H, ArH), 7.38 (q,
J = 8.5, 5.9 Hz, 1H, ArH). 13C NMR (75.46 MHz, CDCl3):
d = 55.7
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(OCH3), 55.8 (OCH3), 60.3 (OCH3), 60.6 (OCH3), 111.4 (d,
J = 15.8 Hz, 2CH), 111.6 (CH), 113.7 (d, J = 21.4 Hz, C), 117.4 (d,
J = 21.9 Hz, C), 122.9 (d, J = 3.4 Hz, 2CH), 123.2 (d, J = 3.4 Hz, 2CH),
123.6 (2CH), 132.2 (d, J = 9.9 Hz, C), 132.8 (C), 134.8 (C), 146.5 (d,
J = 9.6 Hz, C), 146.8 (C), 152.6 (d, J = 10.9 Hz, C), 161.3 (d,
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J = 245.8 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
d
= ꢀ116.3 (CF).
IR (ATR, cmꢀ1): V ¼ 3060 ðwÞ, 2934 (w), 2832 (w), 1738 (w), 1574
(m), 1460 (s), 1397 (m), 1309 (m), 1284 (m), 1256 (s), 1187 (s),
1140 (s), 1081 (s), 1030 (s), 995 (s), 934 (m), 869 (m), 822 (s), 788
(s), 746 (s), 682 (m), 644 (m), 588 (m), 533 (m). MS (GC, 70 eV): m/z
(%) = 368 (100) [M]+, 337 (23), 322 (19), 307 (14), 306 (32), 290 (13)
cmꢀ1. HRMS (EI): calcd. for C22H21O4F [M]+ 368.14184, found
368.14214.
˜
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Acknowledgments
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2267;
Financial support by the State of Pakistan (HEC scholarship for
M. S.) and by the University of Rostock (INF scholarship for S. R.) is
gratefully acknowledged. We are also grateful to the European
Union (EFRE program). The work was also supported by the

36
M. Sharif et al. / Journal of Fluorine Chemistry 146 (2013) 19–36
(b) M. Schnu¨ rch, R. Flasik, A.F. Khan, M. Spina, M.D. Mihovilovic, P. Stanetty, Eur. J. (b) M. Sharif, M. Zeeshan, S. Reimann, A. Villinger, P. Langer, Tetrahedron Lett. 51
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available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be
ordered from the following address: Cambridge Crystallographic Data Centre, 12
Union Road, GB-Cambridge CB21EZ; Fax: (+44) 1223 336 033; or deposit@ccdc.
cam.ac.uk.
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catalyzed cross-coupling reactions based on 1H NMR data of the non-halogenated
derivatives, see: S.T. Handy, Y. Zhang, Chem. Commun. (2006) 299–301.
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