Synthesis of trifluoromethyl-substituted bi- and terphenyls by site-selective Suzuki-Miyaura reactions of various dihalogenated trifluoromethyl-benzene derivatives

Article abstract of DOI:10.1016/j.jfluchem.2012.11.005

A variety of trifluoromethylated bi- and terphenyls were prepared by site-selective Suzuki-Miyaura cross-coupling reactions of various dihalogenated trifluoromethyl-substituted benzene derivatives. The reactions proceed with excellent site-selectivities.

Full text of DOI:10.1016/j.jfluchem.2012.11.005

Journal of Fluorine Chemistry 145 (2013) 18–34
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of trifluoromethyl-substituted bi- and terphenyls by site-selective
Suzuki–Miyaura reactions of various dihalogenated trifluoromethyl-benzene
derivatives
Iftikhar Ali a,b, Baraa Siyo a, Zahid Hassan a, Imran Malik a,c, Ihsan Ullah a,d, Asad Ali a,d
,
a
e
f
a
a,g,
*
´
Muhammad Nawaz , Jamshed Iqbal , Tamas Patonay , Alexander Villinger , Peter Langer
a Institut fu¨r Chemie, Universita¨t Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
b Department of Chemistry, Karakoram International University, Gilgit-Baltistan, Pakistan
c Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, Postal Code 22060, Pakistan
d Department of Chemistry, Abdul Wali Khan University, Mardan, KPK, Pakistan
e Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Postal Code 22060, Pakistan
f Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Egyetem te´r 1, Hungary
g Leibniz-Institut fu¨r Katalyse an der Universita¨t Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
A R T I C L E I N F O
A B S T R A C T
Article history:
A variety of trifluoromethylated bi- and terphenyls were prepared by site-selective Suzuki–Miyaura
cross-coupling reactions of various dihalogenated trifluoromethyl-substituted benzene derivatives. The
reactions proceed with excellent site-selectivities.
Received 1 August 2012
Received in revised form 1 November 2012
Accepted 17 November 2012
Available online 27 November 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Catalysis
Palladium
Suzuki reaction
Organofluorine compounds
Site-selectivity
1. Introduction
compounds with CF3 motif have been reported to exhibit
biologically interesting properties, such as antimalarial activity
Palladium-catalyzed coupling reactions are effective synthetic
tools for the formation of C–C bonds between nucleophilic and
electrophilic substrates concluding into highly substituted arenes
[1] which play a key role in total synthesis of bioactive compounds
[2]. The regioselectivity of Pd-catalyzed cross-coupling reactions of
polyhalogenated arenes has been broadly studied and can provide
a versatile and feasible way for the design and synthesis of libraries
of various functionalized scaffolds [3]. In particular, the Suzuki–
Miyaura cross-coupling reaction has become one of the most
widely used methods for the formation of carbon–carbon bonds
because of the mild reaction conditions and compatibility with a
broad range of functional groups [4]. The trifluoromethyl (CF3)
group is a significant structural motif in many pharmaceutically
[7], antituberculosis agents (mafloquine) [8], and antiviral agents
[9]. Similarly, boxidine is the most efficient nonsteroidal hypo-
cholesteremic agent that is reported to inhibit the biosynthesis of
cholesterol and lowers the cholesterol level (Fig. 1) [10].
Furthermore, fluorine is contained in many liquid crystals which
include twisted nematic liquid crystal displays (TN-LCDs) and
thin-film transistor liquid crystal displays (TFT-LCDs) (Fig. 1) [11].
Recently, we have reported
a convenient synthesis of
trifluoromethyl-substituted biaryls and teraryls by site-selective
Suzuki–Miyaura reactions of 1,4-dibromo-2-trifluoromethylben-
zene [12]. Herein, we report full details of these studies. We have
greatly extended the scope of this approach and herein report
what are, to the best of our knowledge, the first site-selective
Suzuki–Miyaura cross-coupling reactions of 2,4-dichloro-1-(tri-
fluoromethyl)benzene, 1-bromo-4-chloro-2-(trifluoromethyl)-
benzene and 4-bromo-1-chloro-2-(trifluoromethyl)benzene.
These reactions provide a convenient access to a great variety
of trifluoromethylated arenes from simple starting materials. The
products are pharmacologically relevant and are not readily
available by other methods.
relevant molecules [5] having
a wide range of interesting
applications in medicinal and agricultural chemistry [6]. Various
* Corresponding author at: Institut fu¨r Chemie, Universita¨t Rostock, 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.2012.11.005

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
19
CF3
Cl
CF3
Ar1-B(OH)2
F3C
F3C
O
Cl
2
N
Boxidine
TN-LCDs
i
Ar1
3a-m
Cl
1
C5H11
Ar2-B(OH)2
Ar1-B(OH)2
ii
iii
CF3
Fig. 1. Important trifluoromethyl-substituted arenes.
2
2
2. Results and discussion
CF3
Ar2
Ar1
2.1. 2,4-Dichloro-1-(trifluoromethyl)benzene
The Suzuki–Miyaura cross-coupling reactions of commercially
available 2,4-dichloro-1-(trifluoromethyl)benzene (1) with 1.3
equiv. of arylboronic acids 2a–m afforded the biphenyls 3a–m in
moderate to good yields (Scheme 1, Table 1) with excellent site-
selectivity. The best yields were obtained using 1.3 equiv. of the
arylboronic acid, Pd(PPh3)4 (0.05 equiv.) as the catalyst and 2 M aq.
K2CO3 as the base (1,4-dioxane, 80 8C, 6 h). The formation of the
other regioisomer was not observed. The low yield of 3d can be
explained by the steric hindrance of 2,6-dimethylphenylboronic
acid. The low yields of 3j–m can be explained by the presence of
electron-withdrawing substituents Cl, F or CF3 located at the
phenylboronic acids. These substituents result in a decrease of the
nucleophilicity of the boronic acid. In these reactions, the
conversion was not complete and also some decomposition was
observed. The structures of all products were established by NMR,
MS and IR data. The structure of 3c (Fig. 2) was independently
confirmed by X-ray crystal structure analysis [13]. As expected, the
two aryl groups are slightly twisted out of plane, due to steric
reasons.
The Suzuki–Miyaura reactions of 2,4-dichloro-1-(trifluoro-
methyl)benzene (1) with 2.5 equiv. of arylboronic acids 2a–c,k
gave 2,4-diaryl-1-(trifluoromethyl)benzene derivatives 4a–d in
moderate yields. The reactions were carried out at 100 8C in 1,4-
dioxane using 2.5 equiv. of the arylboronic acid, 5 mol% of
Pd(PPh3)4 and an aqueous solution of K2CO3 (2 M) as the base
(Scheme 1, Table 1). It is not surprising that the yields of 4a–d are
lower than the yields of mono-arylated products 3, because two C–
C bonds are formed. In case of 4d, an electron poor (less
nucleophilic) arylboronic acid was employed. In addition, the
Ar1
5a-d
Ar1
4a-d
Scheme 1. Synthesis of 3a–m, 4a–d, and 5a–d. Reagents and conditions: i, 1 (1.0
equiv.), 2 (1.3 equiv.), Pd(PPh3)4 (5 mol%), 2 M K2CO3, 1,4-dioxane, 80 8C, 6 h; ii, 1
(1.0 equiv.), Ar1-B(OH)2 (2.5 equiv.), Pd(PPh3)4 (5 mol%), 2 M K2CO3, 1,4-dioxane,
100 8C, 8 h; iii, 3c (1.0 equiv), Ar2-B(OH)2 (1.3 equiv), Pd(PPh3)4 (5 mol%), aq. K2CO3
(2 M), 1,4-dioxane, 90 8C, 8 h.
steric hindrance exerted by the CF3 group might result in a
decrease of the yield.
The Suzuki–Miyaura reaction of 3-chloro-40-methyl-4-(trifluor-
omethyl)biphenyl (3c) with 1.3 equiv. of arylboronic acids 2e,f,k,n
afforded the disubstituted products 5a–d, containing two different
aryl groups, in moderate to good yields (except for 5c). The relatively
low yields can be again explained by steric effects. The reactions
were carried out in 1,4-dioxane using Pd(PPh3)4 (5 mol%) and an
aqueous solution of K2CO3 (2 M) at 90 8C for 8 h (Scheme 1, Table 1).
The reactionswerecarried out underoptimizedconditions as shown
inTable 3(videinfra). The use ofother solvents (ratherthandioxane)
did not result in an increase of the yield.
2.2. 1,4-Dibromo-2-trifluoromethylbenzene
The Suzuki–Miyaura reaction of commercially available 1,4-
dibromo-2-trifluoromethylbenzene (6) with arylboronic acids 2
Table 1
Synthesis of 3a–m, 4a–d, and 5a–d.
a
a
a
2,3
4
5
Ar1
Ar2
%
(3)
%
(4)
% (5)
a
b
c
a
b
c
2-MeC6H4
–
93
95
97
57
39
60
3-MeC6H4
–
a
b
c
4-MeC6H4
3,5-Me2C6H3
64
40
25
59
4-MeC6H4
4-EtC6H4
4-MeC6H4
4-FC6H4
d
4-MeC6H4
4-(MeO)C6H4
d
e
f
2,6-Me2C6H3
3,5-Me2C6H3
4-EtC6H4
–
–
–
–
–
–
–
–
–
–
36
72
49
56
74
60
47
46
35
32
g
h
i
2-(MeO)C6H4
2,3-(MeO)2C6H3
2,3,4-(MeO)3C6H2
2-ClC6H4
j
k
l
d
4-FC6H4
4-(CF3)C6H4
3-(CF3)C6H4
m
a
Yields of isolated products.

20
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
Fig. 2. ORTEP view of the crystal structure of 3c.
CF3
CF3
Ar2-B(OH)2
Br
Br
2
i
Br
Ar1
Fig. 3. Crystal structure of 7n.
7a-o
6
Ar1-B(OH)2
Ar2-B(OH)2
obtained for products derived from both electron rich and poor
arylboronic acids. The best yields were obtained using exactly 1.0
equiv. of the arylboronic acid, Pd(PPh3)4 (5 mol%) as the catalyst,
and K2CO3 (2 M aqueous solution) as the base. The temperature
also played an important role and was adjusted to 70 8C (1,4-
dioxane, 8 h) (Table 3). The employment of other solvents or bases
resulted in the formation of only trace amounts of product or no
conversion at all. The increase of the temperature resulted in the
formation of mixtures, due to the formation of significant amounts
of terphenyls. The reaction time had only a small effect on the
yields. The structure of 7n was independently confirmed by X-ray
crystal structure analysis (Fig. 3) [13]. The aryl group are twisted
out of plane, due to the steric effect of the methoxy groups.
The Suzuki–Miyaura reaction of 6 with 2.5 equiv. of various
arylboronic acids 2 afforded the 2,5-diaryl-1-(trifluoromethyl)-
benzene derivatives 8a–m in good yields (Scheme 2, Table 2). The
reactions had to be carried out at 90 8C instead of 70 8C to ensure a
complete conversion. Very good yields were again obtained for
products derived from both electron rich and poor arylboronic
acids. The structure of 8l was independently confirmed by X-ray
crystal structure analysis (Fig. 4) [13]. The aryl groups are again
twisted out of plane.
ii
iii
2
2
CF3
CF3
Ar2
Ar1
Ar1
Ar1
8a-m
9a-d
Scheme 2. Synthesis of 7a–o, 8a–m and 9a–d. Conditions: i, 6 (1.0 equiv.), 2 (1.0
equiv.), Pd(PPh3)4 (5 mol%), K2CO3 (H2O, 2 M), 1,4-dioxane, 70 8C, 8 h; ii, 6 (1.0
equiv.), 2 (2.5 equiv.), Pd(PPh3)4 (5 mol%), K2CO3 (H2O, 2 M), dioxane, 90 8C, 8 h; iii, 7
(1.0 equiv.), 2 (1.0 equiv.), Pd(PPh3)4 (5 mol%), K2CO3 (H2O, 2 M), dioxane, 80 8C, 8 h.
(1.0 equiv.) afforded the 4-aryl-1-bromo-2-trifluoromethylben-
zenes 7a–o in 79–94% yields (Scheme 2, Table 2). All reactions
proceeded with very good site-selectivity in favor of position 4. The
products were pure after chromatography. Small amounts (approx.
5–10%) of diarylated products were detected in the crude product
mixture (by 1H NMR) before the separation. Very good yields were
Table 2
Synthesis of 7a–o, 8a–m and 9a–d.
7
a
8
9
a
Ar1
Ar2
% (7)a
% (8)a
% (9)a
a
b
c
d
e
f
2-MeC6H4
–
87
85
86
85
87
87
87
91
82
93
3-MeC6H4
–
4-MeC6H4
–
b
c
3,5-Me2C6H3
4-EtC6H4
–
83
87
3,4-(MeO)2C6H3
88
2,3-(MeO)2C6H3
2,3,4-(MeO)3C6H2
3-(CF3)C6H4
4-(MeO)C6H4
2-ClC6H4
–
d
g
h
i
–
82
–
–
e
f
–
84
80
82
86
84
88
83
79
92
87
94
4-FC6H4
–
g
h
i
j
C6H5
–
84
3-ClC6H4
–
3-(Vinyl)C6H4
4-tBuC6H4
–
j
–
k
l
4-ClC6H4
–
b
2-Naphthyl
2,5-(MeO)2C6H3
2,6-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3-(MeO)C6H4
3,4-(MeO)2C6H4
85
m
n
o
k
l
–
79
95
89
–
c
4-FC6H4
3,5-Me2C6H4
–
80
86
d
m
a
Yields of isolated products.

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
21
Table 3
Optimization of the synthesis of 7j and 7o (Pd(PPh3)4 was used as the catalyst).
Table 4
Synthesis of 1-aryl-4-chloro-2-trifluoromethylbenzenes 11a–i.
Entry
Solvent
Base
T [8C]
t [h]
7o
7j
11
2
Ar
% (11)a
a
a
1
2
Dioxane
THF
2 M K2CO3
2 M K2CO3
2 M K2CO3
3eq. Cs2CO3
3 eq. K3PO4
3 eq. K3PO4
2 M K2CO3
2 M K2CO3
2 M K2CO3
2 M K2CO3
2 M K2CO3
2 M K2CO3
2 M K2CO3
60
60
70
70
70
70
70
90
90
80
75
70
70
8
8
8
8
8
8
8
8
6
6
6
3
8
–
–
a
b
c
d
e
f
a
2-MeC6H4
33
91
42
73
69
61
56
46
22
a
a
–
–
c
4-MeC6H4
a
a
3
DME
–
–
i
2,3,4-(MeO)3C6H2
4-FC6H4
4
Dioxane
Dioxane
Toluene
Toluene
Toluene
Dioxane
Dioxane
THF
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
Traces
k
m
n
o
r
5
3-(CF3)C6H4
4-(MeO)C6H4
C6H5
6
7
g
h
i
8
4-tBuC6H4
3,4-(MeO)2C6H3
b
b
9
–
–
w
b
b
10
11
12
13
–
–
a
Yields of isolated products.
c
c
–
–
Dioxane
Dioxane
87%
94%
82%
88%
stepwise procedure. Therefore, this strategy was not further
studied. The structure of 9b was independently confirmed by X-ray
crystal structure analysis (Fig. 5) [13]. The aryl groups are again
twisted out of plane.
a
No conversion;
b
c
Unseparable mixture of mono- and diarylated products.
Unseparable mixture, mainly diarylated product.
The bromide group of biaryls 7 easily undergoes Suzuki–
2.3. 1-Bromo-4-chloro-2-(trifluoromethyl)benzene and 4-bromo-1-
chloro-2-(trifluoromethyl)-benzene
Miyaura reactions. The reaction of 7c,l,o with arylboronic acids
afforded terphenyls 9a–d in high yields (Scheme 2, Table 2). A one-
pot synthesis of 9a–d starting with substrates 6 also proved to be
possible (sequential addition of two different boronic acids).
However, the yields proved to be lower as compared to the
The Suzuki–Miyaura reaction of commercially available 1-bromo-
4-chloro-2-(trifluoromethyl)benzene (10) with arylboronic acids 2
(1.0 equiv.) afforded the 1-aryl-4-chloro-2-(trifluoromethyl)
Fig. 4. Crystal structure of 8l.
Fig. 5. Crystal structure of 9b.

22
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
Table 5
3. Conclusion
Synthesis of 4-aryl-1-chloro-2-trifluoromethylbenzenes 13a–e.
The site-selective formation of 3a–m can be explained by steric
and electronic reasons. Generally, Suzuki–Miyaura reactions of
polyhalogenated arenes proceed site-selectively by initial oxida-
tive addition of the arylboronic acid at the more electron-deficient
and less sterically-hindered position (Scheme 4) [3]. Position 4 of
2,4-dichloro-1-(trifluoromethyl)benzene 1 is sterically less hin-
dered as compared to position 2 which is located close to the CF3
moiety. The site-selective formation of 7a–o can be explained as
follows: Carbon atom C-4 is sterically less hindered than carbon C-
1, due to its location meta to the CF3 group. Therefore, the first
oxidative addition occurs at position 4. The selective formation of
11a–i and 13a–e is based on the fact that bromine is a better
leaving group than chlorine. The reactivity order of the Suzuki
reaction is generally ArI > ArBr > ArOTf ꢀ ArCl [14].
13
2
Ar
% (13)a
a
b
c
a
c
e
r
2-MeC6H4
4-MeC6H4
3,5-Me2C6H3
4-tBuC6H4
4-BrC6H4
96
87
37
87
45
d
e
x
a
Yields of isolated products.
CF3
Br
CF3
Ar-B(OH)2
Ar1
2
i
Cl
Cl
In conclusion, we have synthesized mono- and diarylated
trifluoromethylbenzene derivatives by site-selective Suzuki–
Miyaura cross-coupling reactions of 2,4-dichloro-1-(trifluoro-
methyl)benzene, 1,4-dibromo-2-trifluoromethyl-benzene, 1-bro-
mo-4-chloro-2-(trifluoromethyl)benzene and 4-bromo-1-chloro-
2-(trifluoromethyl)benzene. These reactions provide a convenient
approach to trifluoromethyl-substituted bi- and terphenyls which
are not readily available by other methods.
10
11a-i
CF3
Cl
CF3
Ar-B(OH)2
Cl
2
ii
Ar1
Br
4. Experimental
4.1. General
12
13a-e
Scheme 3. Synthesis of 11a–i and 13a–e. Conditions: i, 10 (1.0 equiv.), 2 (1.0 equiv.),
Pd(PPh3)4 (5 mol%), K3PO4, 1,4-dioxane, 75 8C, 4 h; ii, 12 (1.0 equiv.), 2 (1.0 equiv.),
Pd(PPh3)4 (5 mol%), K3PO4, 1,4-dioxane, 70 8C, 5 h.
Reactions were carried out under inert atmosphere (Argon).
Solvents for reactions were dried and distilled by standard
methods or purchased from Merck1, Aldrich1, Acros Organics1
,
and others whenever exclusion of water was desired. Solvents for
liquid chromatography and extraction were always distilled prior
to use and partly reused after fractional distillation (n-heptane,
ethyl acetate). Bruker AC 250, Bruker ARX 300, Bruker ARX 500. For
NMR characterization the one-dimensional 1H NMR, proton-
decoupled 13C NMR, and DEPT 135 spectra were collected. If
necessary other techniques (NOESY, COSY, HMQC, and HMBC)
were applied as well. All NMR spectra presented in this work, were
collected in DMSO-d6 and CDCl3solution. All chemical shifts were
benzenes 11a–i in 22–91% yields (Scheme 3, Table 4). All reactions
proceeded with very good chemoselectivity in favor of position 1. The
best yields were obtained using exactly 1.0 equiv. of the arylboronic
acid, Pd(PPh3)4 (5 mol%) as the catalyst, and K3PO4 as the base (1,4-
dioxane, 75 8C, 4 h) (Table 4).
The Suzuki–Miyaura reaction of commercially available 4-
bromo-1-chloro-2-(trifluoromethyl)benzene (12) with arylboro-
nic acids 2 (1.0 equiv.) afforded the 4-aryl-1-chloro-2-(trifluor-
omethyl)benzenes 13a–e in 37–96% yields (Scheme 3, Table 5). All
reactions proceeded with very good chemoselectivity in favor of
position 4. The best yields were obtained using exactly 1.0 equiv. of
the arylboronic acid, Pd(PPh3)4 (5 mol%) as the catalyst, and K3PO4
as the base (1,4-dioxane, 70 8C, 5 h).
given in ppm. References (1H NMR): TMS (
CHCl3
= 7.26) were taken as internal standard. References (13
NMR): TMS ( = 0.0) or residual CHCl3 = 77.0) were taken as
d = 0.00) or residual
(
d
C
d
(d
internal standard. Multiplicities are given as follows: s = singlet,
d = doublet, t = triplet, q = quartet, m = Multiplet, br = broad signal.
More complex coupling patterns are represented by combinations
of the respective symbols. For example, td indicates a triplet of
doublets with the larger coupling constant associated with the first
symbol (here: triplet). Infrared Spectroscopy (IR): Nicolet 205 FT-
CF3
CF3
2
2
Cl
1
´
Br
IR, Nicolet Protege 460 FT-IR Peaks are given the following
Sterically
more
Sterically
more
assignments: w = weak, m = medium, s = strong, br = broad. Mass
Spectrometry (MS): AMD MS40, Varian MAT CH 7, MAT 731 (EI,
70 eV), Intecta AMD 402 (EI, 70 eV and CI), Finnigan MAT 95 (CI,
200 eV). High Resolution Mass Spectrometry (HRMS): Varian MAT
311, Intecta AMD 402. Elemental Analysis: LECO CHNS-932
Thermoquest Flash EA 1112. Melting Points: Micro heating table
HMK 67/1825 Kuestner (Bu¨chi Apparatus). Leitz Labolux 12 Pol
with heating table Mettler FP 90. Melting points are uncorrected.
Thin Layer Chromatography (TLC): Merck Kieselgel 60 F254 on
aluminum foil from Macherey-Nagel. Detection was carried out
under UV light at 254 nm and 365 nm. As colorizing reagent the
following mixtures were used: 1–2/100 p-anisaldehyde or vanillin,
10/100 glacial acetic acid, 5/100 sulphuric acid, 83–84/100
methanol. Column chromatography: Column chromatography
was performed with Merck Silica Gel 60 or Macherey-Nagel Silica
Br
hindered
hindered
Cl
1
Sterically less hindered
Sterically less hindered
CF3
Cl
CF3
1
Br
Better
Br
Better
leaving
group
leaving
Cl
1
group
Scheme 4. Possible explanation for the site-selectivity of cross-coupling reactions
of 1.

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
23
Gel 60 (0.063–0.200 mm, 70–230 mesh). The finer Merck Silica Gel
60 (0.040–0.063 mm, 230–400 mesh) was chosen when appropri-
ate.
135.4 (C), 138.9 (C), 146.1 (C); 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ62.19 (ArCF3); IR (ATR, cmꢁ1):
¼ 3070 (w), 3040 (w), 3029
˜
v
(m), 2921 (m), 2858 (w), 2739 (w), 1916 (w), 1797 (w), 1769 (w),
1602 (s), 1551 (m), 1520 (w), 1489 (m), 1413 (w), 1379 (m), 1356
(w), 1313 (s), 1290 (w), 1270 (w), 1254 (w), 1214 (w), 1187 (w),
1171 (m), 1121 (s), 1105 (s), 1040 (w), 1026 (m), 1014 (w), 959 (m),
904 (w), 887 (m), 845 (w), 836 (m), 808 (s), 785 (m), 740 (m), 717
(w), 676 (m), 643 (w), 624 (w), 588 (m), 561 (m), 547 (w); GC–MS
(EI, 70 eV): m/z (%): 270 (M+, 100), 235 (14), 215 (8), 165 (32), 139
(2), 99 (1), 87 (1), 75 (1), 63 (1), 51 (1), 39 (1); HRMS (EI) calcd for
4.2. General procedure for the synthesis of 3a–m
A 1,4-dioxane solution (8 mL) of 1 (1.0 mmol), arylboronic acid
2 (1.3 equiv.), 2 M K2CO3 (1 mL per cross coupling), and Pd(PPh3)4
(5 mol%) was heated at 80 8C for 6 h. After cooling to room
temperature, H2O was added and the reaction mixture was
extracted with CH2Cl2. The organic layer was dried (Na2SO4),
filtered and concentrated in vacuo. The residue was purified by
column chromatography (pure n-heptane).
C
14H10ClF3 [M+]: 270.04176 found 270.041119.
4.2.4. 30-Chloro-2,6-dimethyl-40-(trifluoromethyl)biphenyl (3d)
Starting with 1 (0.215 g, 1 mmol), 2d (0.194 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3d was isolated as colorless oil (0.102 g, 36%). 1H NMR
4.2.1. 30-Chloro-2-methyl-40-(trifluoromethyl)biphenyl (3a)
Starting with 1 (0.215 g, 1 mmol), 2a (0.176 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-dioxane
(8 mL), 3a was isolated as colorless oil (0.251 g, 93%). 1H NMR
(300.13 MHz, CDCl3):
d = 1.95 (s, 6H, 2CH3), 7.03–7.15 (m, 4H,
ArH), 7.25 (s, 1H, ArH), 7.66 (d, 3J = 7.93 Hz, 1H, ArH); 13C NMR
(300.13 MHz, CDCl3):
d
= 2.31 (s, 3H, CH3), 7.21–7.24 (m, 1H), 7.28–
(62.89 MHz,
CDCl3),
d
= 20.7
(2CH3),
123.0
(CF3,
q,
2
7.37 (m, 4H), 7.52 (s, 1H, ArH), 7.76 (d, 3J = 7.93 Hz, 1H, ArH); 13
C
1JCF = 272.83 Hz), 126.8 (C, q, JCF = 31.59 Hz), 127.60 (2CH),
3
NMR (75.46 MHz, CDCl3),
d
= 20.3 (CH3), 123.1 (CF3, q,
127.64 (CH), 127.7 (CH, q, JCF = 5.49 Hz), 128.0 (CH), 132.0 (CH),
132.4 (C, q, 3JCF = 1.83 Hz), 135.5 (2C), 138.9 (C), 146.6 (C); 19F NMR
(282.40 MHz, CDCl3):
1JCF = 272.89 Hz), 126.1 (CH), 126.8 (C, q, JCF = 31.91 Hz), 127.3
2
3
= ꢁ62.28 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3064
˜
(CH, q, JCF = 4.95 Hz), 127.6 (CH), 128.5 (CH), 129.4 (CH), 130.7
d
(CH), 132.1 (CH), 135.2 (2C), 139.1 (C), 147.2 (C); 19F NMR
(w), 3022 (w), 2953 (w), 2923 (w), 2855 (w), 2739 (w), 1928 (w),
1858 (w), 1787 (w), 1607 (m), 1559 (m), 1500 (w), 1464 (m), 1445
(w), 1384 (m), 1312 (s), 1285 (w), 1251 (m), 1240 (w), 1173 (m),
1126 (s), 1101 (s), 1054 (w), 1028 (s), 988 (w), 964 (w), 919 (w),
889 (m), 834 (s), 769 (s), 758 (w),752 (w), 718 (m), 667 (m), 646
(m), 595 (w), 566 (m), 553 (w); GC–MS (EI, 70 eV): m/z (%): 284
(M+, 100), 269 (25), 249 (73), 234 (28), 180 (22), 165 (38), 152 (4),
139 (1), 105 (1), 89 (2), 39 (1); HRMS (EI) calcd for C15H12ClF3 [M+]:
284.05741 found 284.056674.
= ꢁ62.27 (ArCF3); IR (ATR, cmꢁ1):
¼ 3214
˜
v
(282.40 MHz, CDCl3):
d
(w), 3063 (w), 3021 (w), 2956 (w), 2926 (w), 2865 (w), 2741 (w),
1921 (w), 1804 (w), 1609 (m), 11,602 (m), 1556 (m), 1504 (w),
1481 (w), 1455 (w), 1383 (m), 1312 (s), 1280 (w), 1248 (m), 1173
(m), 1126 (s), 1102 (s), 1054 (w), 1027 (s), 964 (w), 945 (w), 892
(m), 867 (w), 838 (s), 786 (w), 760 (s), 738 (m), 724 (m), 681 (m),
661 (w), 641 (m), 599 (w), 594 (w), 565 (w), 551 (w), 536 (w); GC–
MS (EI, 70 eV): m/z (%): 270 (M+, 100), 235 (11), 215 (27), 165 (80),
139 (3), 115 (3), 91 (3), 69 (5), 63 (3), 39 (2); HRMS (EI) calcd for
C
14H10ClF3 [M+]: 270.04176 found 270.042298.
4.2.5. 3-Chloro-30,50-dimethyl-4-(trifluoromethyl)biphenyl (3e)
Starting with 1 (0.215 g, 1 mmol), 2e (0.194 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3e was isolated as colorless oil (0.204 g, 72%). 1H NMR
4.2.2. 3-Chloro-30-methyl-4-(trifluoromethyl)biphenyl (3b)
Starting with 1 (0.215 g, 1 mmol), 2b (0.176 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3b was isolated as colorless oil (0.257 g, 95%). 1H NMR
(300.13 MHz, CDCl3):
7.43 (m, 3H), 7.56–7.59 (m, 1H), 7.75–7.78 (m, 2H); 13C NMR
(300.13 MHz, CDCl3):
d = 2.43 (s, 6H, 2CH3), 7.11 (s, 1H, ArH), 7.22
(s, 2H, ArH), 7.56 (d, 3J = 8.49 Hz, 1H, ArH), 7.73–7.76 (m, 2H, ArH);
d
= 2.48 (s, 3H, CH3), 7.27–7.30 (m, 1H), 7.39–
13C NMR (62.89 MHz, CDCl3),
d = 21.3 (2CH3), 123.1 (CF3, q,
1JCF = 272.83 Hz), 125.1 (2CH), 125.2 (CH), 126.7 (C, q,
3
(62.89 MHz, CDCl3),
d
= 21.4 (CH3), 123.1 (CF3, q, 1JCF = 272.83 Hz),
2JCF = 31.58 Hz), 127.7 (CH, q, JCF = 5.04 Hz), 129.9 (CH), 130.4
2
124.3 (CH), 125.2 (CH), 126.8 (C, q, JCF = 31.59 Hz), 127.8 (CH, q,
3JCF = 5.04 Hz), 127.9 (CH), 129.0 (CH), 129.6 (CH), 129.9 (CH),
132.6 (C, q, 4JCF = 2.29 Hz), 138.2 (C), 138.9 (2C), 146.3 (C); 19F NMR
˜
(CH), 132.5 (C, q, 3JCF = 1.83 Hz), 138.2 (C), 138.7 (2C), 146.4 (C); 19
F
NMR (282.40 MHz, CDCl3):
d
= ꢁ62.19 (ArCF3); IR (ATR, cmꢁ1):
˜
v
¼ 3016 (w), 2922 (w), 2856 (w), 1602 (m), 1562 (w), 1554 (m),
(282.40 MHz, CDCl3):
d
= ꢁ62.19 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3214
1501 (w), 1493 (w), 1479 (w), 1467 (w), 1443 (w), 1432 (w), 1409
(w), 1379 (w), 1315 (s), 1264 (w), 1212 (w), 1177 (m), 1132 (s),
1108 (m), 1040 (w), 1026 (m), 997 (w), 963 (w), 895 (w), 885 (w),
853 (w), 831 (m), 775 (w), 723 (w), 698 (w), 667 (w), 661 (w), 636
(w), 540 (w); GC–MS (EI, 70 eV): m/z (%): 284 (M+, 100), 269 (23),
249 (11), 234 (14), 165 (18), 152 (2), 105 (1), 51 (1); HRMS (EI)
calcd for HRMS (EI) calcd for C15H12ClF3 [M+]: 284.05741 found
284.057528.
(w), 3027 (w), 2952 (w), 2923 (w), 2864 (w), 2736 (w), 1922 (w),
1883 (w), 1853 (w), 1791 (w), 1698(w), 1674 (w), 1605 (m), 1557
(m), 1503 (m), 1480 (w), 1456 (w), 1427 (w), 1377 (m), 1312 (s),
1299 (w), 1273(w), 1254 (w), 1175 (m), 1126 (s), 1104 (s), 999 (w),
961 (w), 910 (w), 880 (m), 835 (s), 781 (s), 736 (m), 721 (w), 698
(m), 684 (w), 633 (m), 596 (w), 569 (w), 540 (w); GC–MS (EI,
70 eV): m/z (%): 270 (M+, 100), 251 (5), 235 (12), 215 (9), 201 (6),
183 (2), 165 (33), 125 (1), 91 (2), 69 (2), 39 (1); HRMS (EI) calcd for
C
14H10ClF3 [M+]: 270.04176 found 270.041311.
4.2.6. 3-Chloro-40-ethyl-4-(trifluoromethyl)biphenyl (3f)
Starting with 1 (0.215 g, 1 mmol), 2f (0.195 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3f was isolated as colorless oil (0.14 g, 49%). 1H NMR
4.2.3. 3-Chloro-40-methyl-4-(trifluoromethyl)biphenyl (3c)
Starting with 1 (0.215 g, 1 mmol), 2c (0.176 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3c was isolated as white solid (0.262 g, 97%); mp 55–57 8C.
(300.13 MHz, CDCl3):
d = 1.21 (t, J = 7.55 Hz, 3H, CH3), 2.63 (q,
J = 7.55 Hz, J = 15.11 Hz, 2H), 7.22 (d, 3J = 8.50 Hz, 2H, ArH), 7.41–
1H NMR (300.13 MHz, CDCl3):
d
= 2.44 (s, 3H, CH3), 7.31 (d,
7.48 (m, 3H), 7.63–7.66 (m, 2H); 13C NMR (75.46 MHz, CDCl3),
3J = 8.49 Hz, 2H, ArH), 7.50 (d, 3J = 8.12 Hz, 2H, ArH), 7.56 (d,
3J = 8.12 Hz, 1H, ArH), 7.74 (d, 3J = 8.69 Hz, 2H, ArH); 13C NMR
d
= 15.5 (CH3), 28.6 (–CH2–), 123.1 (CF3, q, 1JCF = 272.90 Hz), 124.9
2
(CH), 127.0 (C, q, JCF = 34.66 Hz), 127.1 (2CH), 127.9 (CH, q,
3JCF = 5.50 Hz), 128.7 (2CH), 129.7 (CH), 132.6 (C, q, 3JCF = 1.65 Hz),
135.6 (C), 145.2 (C), 146.1 (C); 19F NMR (282.40 MHz, CDCl3):
˜
(62.89 MHz, CDCl3),
d
= 21.2 (CH3), 123.1 (CF3, q, 1JCF = 275.65 Hz),
124.9 (CH), 126.6 (C, q, 2JCF = 31.36 Hz), 127.0 (2CH), 127.9 (CH, q,
3JCF = 5.50 Hz), 129.6 (CH), 129.9 (2CH), 132.6 (C, q, 3JCF = 1.65 Hz),
d
= ꢁ62.19 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3026 (w), 2966 (w), 2932

24
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
(w), 2874 (m), 1907 (w), 1579 (w), 1605 (m), 1576 (w), 1552 (m),
1523 (w), 1488 (w), 1461 (w), 1455 (w), 1420 (m), 1382 (m), 1312
(s), 1293 (w), 1254 (w), 1175 (m), 1127 (s), 1103(s), 1059 (w), 1042
(w), 1025 (m), 1015 (m), 962 (w), 887 (m), 820 (s), 772 (w), 736
(m), 699 (w), 674 (m), 644(w), 624 (w), 594 (m), 561 (m), 532 (w);
GC–MS (EI, 70 eV): m/z (%): 284 (M+, 50), 271 (32), 269 (100), 249
(4), 233 (7), 165 (19), 117 (1), 77 (1), 63 (1), 39 (1); HRMS (EI) calcd
for C15H12ClF3 [M+]: 284.05741 found 284.056982.
1552 (m), 1509 (m), 1484 (m), 1462 (m), 1434 (w), 1416 (m), 1378
(m), 1313 (w), 1304 (s), 1293 (w), 1257 (w), 1234 (m), 1211 (m),
1175 (s), 1127 (m), 1104 (s), 1084 (s), 1025 (w), 1009 (s), 927 (m),
883 (m), 838 (m), 794 (s), 759 (w), 737 (m), 697 (w), 689 (w), 654
(w), 621 (w), 603 (w), 585 (w), 539 (w); GC–MS (EI, 70 eV): m/z (%):
346 (M+, 100), 331 (16), 296 (31), 288 (19), 217 (29), 182 (6), 167
(2), 132 (1), 99 (2), 69 (2); HRMS (EI) calcd for C16H14ClF3O3 [M+]:
346.05781 found 346.056833.
4.2.7. 30-Chloro-2-methoxy-40-(trifluoromethyl)biphenyl (3g)
Starting with 1 (0.215 g, 1 mmol), 2g (0.198 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3g was isolated as heavy oil (0.16 g, 56%). 1H NMR
4.2.10. 2,30-Dichloro-40-(trifluoromethyl)biphenyl (3j)
Starting with 1 (0.215 g, 1 mmol), 2j (0.202 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3j was isolated as colorless oil (0.135 g, 47%). 1H NMR
(300.13 MHz, CDCl3):
ArH), 7.21 (dd, J = 7.55 Hz, J = 1.89 Hz, 1H, ArH), 7.28–7.34 (m, 1H,
ArH), 7.42–7.45 (m, 1H, ArH), 7.60–7.64 (m, 2H, ArH); 13C NMR
d
= 3.75 (s, 3H, OCH3), 6.91–6.99 (m, 2H,
(300.13 MHz, CDCl3): d = 7.24–7.29 (m, 3H, ArH), 7.35–7.38 (m, 1H,
ArH), 7.40–7.43 (m, 1H, ArH), 7.51 (s, 1H, ArH), 7.66 (d, 3J = 8.12 Hz,
1H, ArH); 13C NMR (62.89 MHz, CDCl3),
d
= 122.9 (CF3, q,
2
(62.89 MHz, CDCl3),
d
= 55.5 (OCH3), 111.4 (CH), 121.0 (CH), 123.1
1JCF = 273.29 Hz), 128.0 (C, q, JCF = 33.42 Hz), 127.1 (CH), 127.2
(CF3, q, 1JCF = 272.83 Hz), 126.5 (C, q, 2JCF = 31.59 Hz), 127.0 (CH, q,
3JCF = 5.49 Hz), 127.7 (CH, C), 130.0 (CH), 130.6 (CH), 131.7 (C, q,
3JCF = 1.83 Hz), 132.3 (CH), 143.7 (C), 156.4 (C); 19F NMR
˜
(CH, q, JCF = 5.49 Hz), 127.8 (CH), 129.7 (CH), 130.2 (CH), 130.9
3
3
(CH), 132.0 (C, q, JCF = 1.83 Hz), 132.2 (C), 132.3 (CH), 137.7 (C),
144.3 (C); 19F NMR (282.40 MHz, CDCl3):
(ATR, cmꢁ1):
d
= ꢁ62.40 (ArCF3); IR
= ꢁ62.25 (ArCF3); IR (ATR, cmꢁ1):
v
¼
¼ 3061 (w), 2924 (w), 2854 (w), 1923 (w), 1807 (w),
˜
v
(282.40 MHz, CDCl3):
d
3069 (w), 3002 (w), 2941 (w), 2836 (w), 1605 (m), 1581 (w), 1555
(w), 1504 (m), 1482 (m), 1463 (m), 1435 (m), 1386 (m), 1311 (s),
1277 (w), 1251 (m), 1238 (m), 1175 (m), 1120 (s), 1103 (s), 1056
(w), 1025 (s), 1003 (w), 963 (w), 935 (w), 889 (m), 851 (w), 833 (m),
784 (m), 748 (s), 731 (w), 682 (m), 635 (m), 615 (w), 593 (w), 574
(w), 566 (w), 554 (m); GC–MS (EI, 70 eV): m/z (%): 286 (M+, 100),
267 (7), 251 (19), 236 (59), 217 (13), 202 (21), 152 (4), 139 (12),
118 (19), 99 (3), 87 (7), 39 (2); HRMS (EI) calcd for C14H10ClF3O
[M+]: 286.03688 found 286.036464.
1607 (m), 1569 (m), 1556 (w), 1503 (m), 1468 (m), 1435 (m), 1385
(m), 1311 (s), 1264 (w), 1244 (w), 1174 (m), 1125 (s), 1103 (m),
1077 (m), 1050 (w), 1037(s), 1027 (m), 981 (w), 962 (w), 947 (w),
891 (m), 865 (w), 834 (s), 756 (m), 749 (m), 740 (w), 731 (w),
705(m), 671 (m), 636 (m), 598 (w), 562 (w), 557(w), 542 (w); GC–
MS (EI, 70 eV): m/z (%): 290 (M+, 100), 271 (5), 255 (4), 235 (10),
220 (25), 201 (5), 186 (12), 170 (4), 150 (5), 123 (1), 99 (2), 50 (1);
HRMS (EI) calcd for C13H7Cl2F3 [M+]: 289.98714 found 289.987078.
4.2.11. 3-Chloro-40-fluoro-4-(trifluoromethyl)biphenyl (3k)
4.2.8. 30-Chloro-2,3-dimethoxy-40-(trifluoromethyl)biphenyl (3h)
Starting with 1 (0.215 g, 1 mmol), 2h (0.237 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3h was isolated as colorless oil (0.235 g, 74%). 1H NMR
Starting with 1 (0.215 g, 1 mmol), 2k (0.181 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3k was isolated as white solid (0.127 g, 46%); mp 67–69 8C.
1H NMR (300.13 MHz, CDCl3):
d = 7.02–7.11 (m, 2H, ArH), 7.37–
(300.13 MHz, CDCl3):
d
= 3.53 (s, 3H, OCH3), 3.79 (s, 3H, OCH3),
7.48 (m, 3H, ArH), 7.58 (s, 1H, ArH), 7.63 (d, 3J = 8.31 Hz, 1H, ArH);
2
6.78–6.81 (m, 1H, ArH), 6.85 (dd, J = 8.31 Hz, J = 1.51 Hz, 1H, ArH,
ArH), 6.98–7.03 (m, 1H, ArH), 7.42–7.45 (m, 1H, ArH), 7.59–7.61
13C NMR (75.46 MHz, CDCl3),
d
= 116.2 (2CH, d, JCF = 22.01 Hz),
1
123.0 (CF3, q, JCF = 272.90 Hz), 125.0 (CH), 128.0 (CH, q,
(m, 2H, ArH); 13C NMR (62.89 MHz, CDCl3),
d
= 55.9 (OCH3), 60.8
3JCF = 4.95 Hz), 128.9 (2CH, d, JCF = 8.25 Hz), 127.0 (C, q,
3
1
3
(OCH3), 112.9 (CH), 122.0 (CH), 123.1 (CF3, q, JCF = 272.89 Hz),
2JCF = 31.91 Hz), 129.8 (CH), 132.8 (C, q, JCF = 1.65 Hz), 134.4 (C,
2
124.5 (CH), 126.8 (C, q, JCF = 31.91 Hz), 127.2 (CH, q,
d, 4JCF = 3.30 Hz), 145.1 (C), 163.3 (CF, d, 1JCF = 249.24 Hz); 19F NMR
3JCF = 4.95 Hz), 127.6 (CH), 131.8 (C, q, JCF = 1.65 Hz), 132.1
(282.40 MHz, CDCl3):
d
= ꢁ62.28 (ArCF3), ꢁ112.95 (ArF); IR (ATR,
3
(CH), 132.9 (C), 143.5 (C), 146.6 (C), 153.3 (C); 19F NMR
cmꢁ1):
v
¼ 3075 (w), 3049 (w), 2924 (w), 2856 (w), 1890 (w), 1605
˜
˜
(282.40 MHz, CDCl3):
d
= ꢁ62.23 (ArCF3); IR (ATR, cmꢁ1):
v
¼
(m), 1598 (m), 1561 (w), 1521 (w), 1495 (m), 1489 (m), 1421 (w),
1383 (m), 1313 (s), 1290 (w), 1232 (s), 1179 (w), 1160 (w), 1126 (s),
1105 (s), 1059(w), 1038 (w), 1024 (m), 1014 (w), 959 (w), 884 (m),
839 (w), 820 (s), 804 (m), 764 (w), 738 (m), 712 (w), 701(w), 675
(m), 712 (w), 701 (w), 675 (m), 637 (w), 619 (w), 593 (m), 560 (m),
546 (w); GC–MS (EI, 70 eV): m/z (%): 274 (M+, 100), 238 (4), 219
(15), 170 (19), 120 (1), 94 (3), 85 (1), 75 (2), 69 (1); HRMS (EI) calcd
for C13H7ClF4 [M+]: 274.01669 found 274.016090.
3030 (w), 2966 (m), 2933 (w), 2874 (w), 1907 (w), 1606 (m), 1579
(w), 1516 (w), 1474 (m), 1415 (w), 1399 (m), 1377 (w), 1330 (s),
1283 (m), 1255 (m), 1167 (s), 1123 (s), 1087 (s), 1065 (w), 1029
(m), 1014 (m), 965 (w), 904 (m), 842 (w), 825 (s), 774 (w), 731 (w),
717 (m), 677 (w), 657 (m), 632 (m), 598 (m), 581 (w), 554 (m); GC–
MS (EI, 70 eV): m/z (%): 316 (M+, 100), 301 (17), 266 (92), 251 (12),
223 (10), 204 (8), 169 (6), 141 (2), 126 (2), 99 (1), 69 (3); HRMS (EI)
calcd for C15H12ClF3O2 [M+]: 316.04724 found 316.046783.
4.2.12. 3-Chloro-4,40-bis(trifluoromethyl)biphenyl (3l)
4.2.9. 30-Chloro-2,3,4-trimethoxy-40-(trifluoromethyl)biphenyl (3i)
Starting with 1 (0.215 g, 1 mmol), 2i (0.276 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3i was isolated as colorless oil (0.207 g, 60%). 1H NMR
Starting with 1 (0.215 g, 1 mmol), 2l (0.246 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3l was isolated as colorless oil (0.114 g, 35%). 1H NMR
(300.13 MHz, CDCl3): d = 7.47–7.50 (m, 1H, ArH), 7.59–7.72 (m, 6H,
(300.13 MHz, CDCl3):
d
= 3.61 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 3.82
ArH); 13C NMR (75.46 MHz, CDCl3),
d = 122.8 (CF3, q,
1
(s, 3H, OCH3), 6.63 (d, J = 8.69 Hz, 1H, ArH), 6.89 (d, J = 8.69 Hz, 1H,
ArH), 7.34 (d, J = 8.12 Hz, 1H, ArH), 7.56–7.59 (m, 2H, ArH); 13C
1JCF = 272.90 Hz), 124.0 (CF3, q, JCF = 271.80 Hz), 125.4 (CH),
3
127.6 (2CH), 126.1 (2CH, q, JCF = 3.85 Hz), 128.2 (CH, q,
2
NMR (75.46 MHz, CDCl3),
d
= 55.9 (OCH3), 60.9 (OCH3), 61.1
3JCF = 5.50 Hz), 130.1 (CH), 130.9 (2C, q, JCF = 32.46 Hz), 133.0
1
3
(OCH3), 107.7 (CH), 122.5 (CF3, q, JCF = 272.89 Hz), 124.6 (CH),
125.6 (C), 126.2 (C, q, 2JCF = 31.36 Hz), 127.1 (CH, q, 3JCF = 5.50 Hz),
127.3 (CH), 131.8 (CH), 142.7 (C), 143.4 (C), 151.4 (C), 153.5 (C),
(C, q, JCF = 1.65 Hz), 141.8 (C), 144.6 (C); 19F NMR (282.40 MHz,
˜
CDCl3):
d
= ꢁ62.45 (ArCF3), ꢁ62.69 (ArCF3); IR (ATR, cmꢁ1):
v
¼
2934 (w), 1924 (w), 1737 (w), 1607 (m), 1557 (m), 1492 (w), 1421
(w), 1381 (m), 1313 (s), 1257 (w), 1165 (w), 1105 (s), 1069 (s), 1038
(w), 1025 (m), 1014 (m), 964 (w), 956 (w), 890 (m), 850 (w), 824
154.3 (C); 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ62.18 (ArCF3); IR
(ATR, cmꢁ1):
¼ 2995 (w), 2938 (w), 2837 (w), 1740 (w), 1596 (s),
˜
v

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
25
(s), 771 (w), 742 (w), 732 (w), 693 (m), 653 (m), 625 (w), 598 (m),
(300.13 MHz, CDCl3):
7.05–7.14 (m, 4H), 7.19–7.35 (m, 4H), 7.46 (s, 1H), 7.54–7.58 (m,
1H), 7.69 (d, 3J = 8.31 Hz, 1H, ArH); 13C NMR (62.89 MHz, CDCl3),
d
= 2.32 (s, 3H, CH3), 2.33 (s, 3H, CH3),
558 (w), 543 (w); GC–MS (EI, 70 eV): m/z (%): 324 (M+, 100), 305
(18), 274 (8), 220 (14), 170 (3), 144 (1), 112 (2), 99 (1), 75 (1), 69
(2); HRMS (EI) calcd for C14H7ClF6 [M+]: 324.01350 found
324.013171.
1
d
= 21.4 (CH3), 21.5 (CH3), 124.3 (CF3, q, JCF = 273.74 Hz), 124.4
3
(CH), 125.7 (CH), 126.1 (CH), 126.5 (CH, q, JCF = 5.04 Hz), 127.1
2
(C, q, JCF = 30.21 Hz), 127.7 (CH), 128.0 (CH), 128.4 (CH), 128.8
4.2.13. 3-Chloro-30,4-bis(trifluoromethyl)biphenyl (3m)
(CH), 128.9 (CH), 129.7 (CH), 130.7 (CH), 137.4 (C), 138.6 (C),
139.4 (C), 139.9 (C), 141.9 (C, q, JCF = 1.83 Hz), 144.2 (C); 19F
4
Starting with 1 (0.215 g, 1 mmol), 2m (0.246 g, 1.3 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(8 mL), 3m was isolated as colorless oil (0.103 g, 32%). 1H NMR
NMR (282.40 MHz, CDCl3):
d
= ꢁ56.54 (ArCF3); IR (ATR, cmꢁ1):
IR (ATR, cmꢁ1):
¼ 3030 (m), 2922 (m), 2853 (w), 2732 (w),
˜
v
(300.13 MHz, CDCl3):
d
= 7.49–7.61 (m, 3H, ArH), 7.64–7.74 (m, 4H,
1943 (w), 1876 (w), 1788 (w), 1726 (w), 1603 (m), 1585 (w),
1567 (m), 1479 (m), 1454 (w), 1379 (m), 1309 (s), 1267 (w),
1165 (m), 1117 (s), 1096 (w), 1078 (m), 1031 (s), 999 (w), 962
(w), 895 (w), 881 (w), 835 (m), 783 (s), 758 (w), 734 (w), 703 (s),
694 (w), 643 (m), 611 (w), 589 (m), 563 (w); GC–MS (EI, 70 eV):
m/z (%): 326 (M+, 100), 305 (11), 291 (5), 257 (3), 165 (3), 128
(1), 91 (1); HRMS (EI) calcd for C21H17F3 [M+]: 326.12769 found
326.127119.
ArH); 13C NMR (62.89 MHz, CDCl3),
d = 122.8 (CF3, q,
1JCF = 273.29 Hz), 123.9 (CF3, q, JCF = 272.37 Hz), 123.9 (CH, q,
1
3JCF = 4.12 Hz), 124.7 (CH, q, 3JCF = 3.66 Hz), 125.3 (CH), 125.4 (CH,
3
q, JCF = 3.66 Hz), 129.7 (CH), 130.0 (CH), 130.5 (CH), 131.5 (C, q,
2JCF = 32.04 Hz), 131.7 (C, q, JCF = 32.50 Hz), 133.1 (C, q,
2
3JCF = 1.83 Hz), 139.1 (C), 144.6 (C); 19F NMR (282.40 MHz, CDCl3):
˜
v
d
= ꢁ62.43 (ArCF3), ꢁ62.72 (ArCF3); IR (ATR, cmꢁ1):
¼ 3071 (w),
3051 (w), 2926 (w), 1608 (m), 1565 (w), 1510 (w), 1503 (w), 1484
(w), 1443 (m), 1412 (w), 1385 (m), 1334 (m), 1314 (s), 1289 (w),
1267 (m), 1255 (m), 1167 (m), 1120 (s), 1104 (s), 1074 (m),
1049(m), 1026 (m), 1001 (w), 963 (w), 922 (w), 908 (w), 885 (m),
862 (m), 837 (m), 798 (s), 782 (w), 762 (w), 695(s), 674 (w), 665
(w), 659 (w), 636 (w), 620 (w), 591 (w), 557 (w), 544 (w); GC–MS
(EI, 70 eV): m/z (%): 324 (M+, 100), 305 (15), 274 (6), 220 (13), 170
(3), 145 (1), 109 (1), 99 (1), 75 (1), 69 (2); HRMS (EI) calcd for
4.3.3. 4-Trifluoromethyl-1,3-bis(4-methylphenyl)-benzene (4c)
Starting with 1 (0.215 g, 1 mmol), 2c (0.337 g, 2.5 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (2 mL), 1,4-Dioxane
(8 mL), 4c was isolated as colorless oil (0.196 g, 60%). 1H NMR
(300.13 MHz, CDCl3):
d = 2.29 (s, 3H, CH3), 2.32 (s, 3H, CH3), 7.11–
7.20 (m, 6H, ArH), 7.37–7.44 (m, 3H, ArH), 7.51–7.55 (m, 1H, ArH),
7.66 (d, 3J = 8.12 Hz, 1H, ArH); 13C NMR (62.89 MHz, CDCl3),
1
C
14H7ClF6 [M+]: 324.01350 found 324.013577.
d
= 21.2 (CH3), 21.3 (CH3), 124.4 (CF3, q, JCF = 274.20 Hz), 125.4
3
(CH), 126.6 (CH, q, JCF = 5.49 Hz), 126.8 (CH), 127.0 (C, q,
2JCF = 30.21 Hz), 127.1 (2CH), 128.6 (CH), 128.89 (CH, q,
5JCF = 1.37 Hz), 129.5 (CH), 129.7 (2CH), 130.6 (CH), 136.6 (C),
136.7 (C), 137.0 (C), 138.2 (C), 141.9 (C), 144.0 (C); 19F NMR
˜
4.3. General procedure for synthesis of 4a–d
A 1,4-Dioxane solution (8 mL) of 1 (1.0 equiv.), arylboronic acid
2 (2.5 equiv.), 2 M K2CO3 (2 mL), and Pd(PPh3)4 (5 mol%) was
heated at 110 8C for 8 h. After cooling to room temperature, H2O
was added and the reaction mixture was extracted with CH2Cl2.
The organic layer was dried (Na2SO4), filtered and concentrated in
vacuo. The residue was purified by column chromatography
(gradient elution n-heptane/ethyl acetate).
(282.40 MHz, CDCl3):
d
= ꢁ56.47 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3024
(w), 2921 (m), 2856 (w), 2732 (w), 2620 (w), 2590 (w), 1904 (m),
1798 (w), 1732 (w), 1652 (w), 1607 (s), 1578 (w), 1561 (w), 1515
(m), 1500 (w), 1490 (m), 1455 (w), 1417 (w), 1383 (m), 1348 (w),
1307 (s), 1281 (w), 1264 (w), 1211 (w), 1170 (s), 1118 (s), 1111 (s),
1075 (s), 1029 (s), 1008 (m), 963 (w), 945 (w), 901 (m), 841 (m),
809 (s), 801 (m), 779 (w), 758 (m), 738 (w), 720 (m), 698 (w), 679
(w), 653 (w), 641 (w), 626 (w), 606 (w), 586 (m), 565 (w), 540 (m);
GC–MS (EI, 70 eV): m/z (%): 326 (M+, 100), 286 (1), 257 (4), 215 (2),
165 (3), 91 (2); HRMS (EI) calcd for C21H17F3 [M+]: 326.12769
found 326.127380.
4.3.1. 4-Trifluoromethyl-1,3-bis(2-methylphenyl)-benzene (4a)
Starting with 1 (0.215 g, 1 mmol), 2a (0.337 g, 2.5 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (2 mL), 1,4-Dioxane
(8 mL), 4a was isolated as colorless oil (0.186 g, 57%). 1H NMR
(300.13 MHz, CDCl3):
d = 2.01 (s, 3H, CH3), 2.20 (s, 3H, CH3),
7.09–7.19 (m, 9H), 7.34 (qd, J = 8.12 Hz, J = 0.94 Hz, 1H, ArH),
4.3.4. 4-Trifluoromethyl-1,3-bis(4-fluorophenyl)-benzene (4d)
Starting with 1 (0.215 g, 1 mmol), 2k (0.348 g, 2.5 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (2 mL), 1,4-Dioxane
(8 mL), 4d was isolated as colorless oil (0.165 g, 49%). 1H NMR
7.70 (d, 3J = 7.93 Hz, 1H, ArH); 13C NMR (62.89 MHz, CDCl3),
1
d
= 20.1 (CH3), 20.4 (CH3), 124.2 (CF3, q, JCF = 273.74 Hz), 124.9
3
(CH), 125.9 (CH), 126.0 (CH, q, JCF = 5.04 Hz), 127.2 (C, q,
2JCF = 29.76 Hz), 127.91 (CH), 127.98 (CH), 128.0 (CH), 129.5
(CH), 129.6 (2CH), 130.6 (CH), 132.4 (CH), 135.2 (C), 135.9 (C),
(300.13 MHz, CDCl3):
2H, ArH), 7.39 (s, 1H, ArH), 7.48–7.57 (m, 3H, ArH), 7.71 (d,
3J = 8.12 Hz, 1H, ArH); 13C NMR (75.46 MHz, CDCl3),
= 114.9
d = 6.99–7.09 (m, 4H, ArH), 7.24–7.28 (m,
138.9 (C), 140.2 (C), 140.5 (C, q, JCF = 2.29 Hz), 145.1 (C); 19F
d
4
2
2
NMR (282.40 MHz, CDCl3):
˜
v
d
= ꢁ58.80 (ArCF3); IR (ATR, cmꢁ1):
(2CH, d, JCF = 22.01 Hz), 116.0 (2CH, d, JCF = 21.46 Hz), 124.2
(CF3, q, 1JCF = 273.45 Hz), 125.9 (CH), 126.8 (CH, q, 3JCF = 5.50 Hz),
127.4 (C, q, JCF = 30.26 Hz), 128.9 (2CH, d, JCF = 8.25 Hz), 130.6
(2CH), 130.7 (C, q, JCF = 1.65 Hz), 135.4 (C, d, JCF = 3.30 Hz),
135.6 (C, d, JCF = 3.30 Hz), 140.9 (C, q, JCF = 1.65 Hz), 143.2 (C),
162.6 (CF, d, 1JCF = 247.04 Hz), 163.1 (CF, d, 1JCF = 248.14 Hz); 19
¼ 3061 (w), 3020 (w), 2953 (w), 2923 (w), 2858 (w), 2738 (w),
2
3
2620 (w), 2576 (w), 1917 (w), 1806 (w), 1727 (w), 1609 (m),
1601 (m), 1564 (m), 1507 (w), 1479 (m), 1455 (m), 1390 (m),
1310 (s), 1256 (w), 1168 (s), 1116 (s), 1070 (m), 1044 (w), 1030
(m), 1009 (m), 985 (w), 964 (w), 943 (w), 908 (s), 866 (w), 839
(s), 768 (m), 754 (s), 739 (m), 724 (s), 692 (m), 653 (m), 639 (m),
630 (m), 597 (m), 557 (m), 539 (m); GC–MS (EI, 70 eV): m/z (%):
326 (M+, 100), 311 (9), 285 (5), 257 (19), 242 (10), 215 (7), 165
(12), 105 (2), 91 (3), 65 (1); HRMS (EI) calcd for C21H17F3 [M+]:
326.12769 found 326.127047.
3
4
4
3
F
NMR (282.40 MHz, CDCl3):
d
= ꢁ56.73 (ArCF3), ꢁ113.77 (ArF),
ꢁ114.50 (ArF); IR (ATR, cmꢁ1):
¼ 3046 (w), 2923 (w), 2854
˜
v
(w), 1894 (w), 1608 (m), 1568 (w), 1511 (m), 1490 (m), 1405
(w), 1384 (w), 1309 (s), 1264 (w), 1224 (m), 1174 (w), 1117 (s),
1095 (w), 1076 (m), 1030 (m), 1010 (w), 961 (w), 903 (w),
822 (s), 790 (m), 721 (m), 679 (m), 635 (w), 621 (w), 605 (w),
585 (w), 563 (m), 542 (m); GC–MS (EI, 70 eV): m/z (%): 334 (M+,
100), 313 (7), 264 (9), 244 (6), 219 (7), 167 (6), 122 (2), 75 (1);
HRMS (EI) calcd for C19H11F5 [M+]: 334.07754 found
334.077305.
4.3.2. 4-Trifluoromethyl-1,3-bis(3-methylphenyl)-benzene (4b)
Starting with 1 (0.215 g, 1 mmol), 2b (0.337 g, 2.5 equiv.),
Pd(PPh3)4 (0.058 g, 0.05 equiv.), 2 M K2CO3 (2 mL), 1,4-Dioxane
(8 mL), 4b was isolated as colorless oil (0.126 g, 39%). 1H NMR

26
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
4.4. General procedure for synthesis of 5a–d
(75.46 MHz, CDCl3), d
= 21.2 (CH3), 114.8 (2CH, d, 2JCF = 21.46 Hz),
1
124.3 (CF3, q, JCF = 273.45 Hz), 125.8 (CH), 126.7 (CH, q,
2
A 1,4-dioxane solution (8 mL) of 3 (1.0 equiv.), arylboronic acid
2 (1.3 equiv.), 2 M K2CO3 (1 mL), and Pd(PPh3)4 (5 mol%) was
heated at 110 8C for 8 h. After cooling to room temperature, H2O
was added and the reaction mixture was extracted with CH2Cl2.
The organic layer was dried (Na2SO4), filtered and concentrated in
vacuo. The residue was purified by column chromatography
(gradient elution n-heptane/ethyl acetate).
3JCF = 4.95 Hz), 127.1 (2CH), 127.5 (C, q, JCF = 30.81 Hz), 129.7
3
(2CH), 130.5 (CH), 130.7 (2CH, d, JCF = 8.25 Hz), 135.8 (C, d,
3
4JCF = 3.30 Hz), 136.4 (C), 140.8 (C, q, JCF = 2.20 Hz), 138.3 (C),
1
144.2 (C), 162.5 (CF, d, JCF = 247.04 Hz); 19F NMR (282.40 MHz,
˜
v
CDCl3):
d
= ꢁ56.64 (ArCF3), ꢁ114.74 (ArF); IR (ATR, cmꢁ1):
¼
3028 (w), 2923 (w), 2859 (w), 2733 (w), 1901 (w), 1741 (w), 1606
(m), 1563 (w), 1512 (m), 1490 (m), 1417 (w), 1308 (s), 1282 (w),
1224 (m), 1172 (m), 1117 (s), 1076 (m), 1030 (m), 1010 (w), 962
(w), 837 (m), 810 (s), 783 (w), 741 (w), 702 (w), 639 (w), 624 (w),
587 (w), 564 (w), 542 (w); GC–MS (EI, 70 eV): m/z (%): 330 (M+,
100), 289 (3), 261 (7), 246 (5), 220 (2), 183 (2), 165 (10), 144 (3),
109 (1), 91 (3), 89 (1), 75 (1), 63 (1), 51 (1), 39 (1); HRMS (EI) calcd
for C20H14F4 [M+]: 330.10261 found 330.102661.
4.4.1. 1-(40-Methylphenyl)-3-(300,500-dimethylphenyl)-4-
trifluoromethylbenzene (5a)
Starting with 3c (0.08 g, 0.3 mmol), 2e (0.058 g, 1.3 equiv.),
Pd(PPh3)4 (0.017 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(4 mL), 5a was isolated as colorless oil (0.065 g, 64%). 1H NMR
(300.13 MHz, CDCl3):
d = 2.28 (s, 6H, 2CH3), 2.31 (s, 3H, CH3), 6.92
(s, 2H, ArH), 6.96 (s, 1H, ArH), 7.17 (d, 3J = 8.50 Hz, 2H, ArH), 7.42–
7.45 (m, 3H, ArH), 7.53–7.56 (m, 1H, ArH), 7.68 (d, 3J = 8.31 Hz, 1H,
4.4.4. 1-(40-Methylphenyl)-3-(400-methoxyphenyl)-4-
trifluoromethylbenzene (5d)
Starting with 3c (0.08 g, 0.3 mmol), 2n (0.059 g, 1.3 equiv.),
Pd(PPh3)4 (0.017 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(4 mL), 5d was isolated as colorless oil (0.06 g, 59%). 1H NMR
ArH); 13C NMR (62.89 MHz, CDCl3),
d
= 21.1 (CH3), 21.3 (2CH3),
1
124.4 (CF3, q, JCF = 271.91 Hz), 125.3 (CH), 126.4 (C, q,
2JCF = 30.67 Hz), 126.6 (CH, q, JCF = 5.49 Hz), 126.8 (2CH, q,
3
5JCF = 1.37 Hz), 127.1 (2CH), 129.3 (CH), 129.7 (2CH), 130.5 (CH),
136.6 (C), 137.2 (2C), 138.2 (C), 139.9 (C), 142.1 (C, q,
3JCF = 1.83 Hz), 143.9 (C); 19F NMR (282.40 MHz, CDCl3):
˜
(300.13 MHz, CDCl3): d = 2.31 (s, 3H, CH3), 3.76 (s, 3H, OCH3), 6.86
(d, 3J = 8.69 Hz, 2H, ArH), 7.15–7.24 (m, 4H, ArH), 7.39–7.44 (m, 3H,
ArH), 7.52–7.55 (m, 1H, ArH), 7.68 (d, 3J = 8.12 Hz, 1H, ArH); 13C
d
= ꢁ56.51 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3023 (w), 2952 (w),
NMR (62.89 MHz, CDCl3), d = 21.1 (CH3), 55.3 (OCH3), 113.3 (2CH),
1
2919 (m), 2862 (w), 2735 (w), 1917 (w), 1598 (m), 1562 (w), 1470
(w), 1381 (w), 1307 (s), 1281 (m), 1192 (w), 1161 (m), 1119 (s),
1095 (w), 1027 (m), 964 (w), 900 (w), 858 (m), 811 (s), 772 (w), 717
(w), 704 (m), 659 (w), 646 (w), 633 (w), 589 (m), 541 (w); GC–MS
(EI, 70 eV): m/z (%): 340 (M+, 100), 305 (7), 271 (4), 256 (5), 239 (5),
170 (4), 162 (5), 141 (1), 127 (3), 105 (3), 91 (2), 77 (1), 65 (1), 51
(1), 39 (1); HRMS (EI) calcd for C22H19F3 [M+]: 340.14334 found
340.143000.
124.4 (CF3, q, JCF = 273.74 Hz), 125.3 (CH), 126.6 (CH, q,
2
3JCF = 5.49 Hz), 127.0 (C, q, JCF = 29.76 Hz), 127.1 (2CH), 129.7
5
(2CH), 130.2 (2CH, q, JCF = 1.37 Hz), 130.7 (CH), 132.3 (C), 136.5
3
(C), 138.2 (C), 141.6 (C, q, JCF = 1.83 Hz), 144.0 (C), 159.2 (C); 19F
NMR (282.40 MHz, CDCl3):
d
= ꢁ56.56 (ArCF3); IR (ATR, cmꢁ1):
˜
v
¼ 3030 (w), 3000 (w), 2934 (w), 2836 (w), 1607 (m), 1562 (w),
1510 (m), 1463 (w), 1385 (w), 1307 (s), 1291 (w), 1243 (m), 1170
(m), 1116 (s), 1107 (s), 1076 (m), 1029 (s), 1004 (w), 962 (w), 930
(m), 809 (s), 762 (w), 679 (w), 624 (w), 606 (w), 587 (w), 573 (w),
545 (w); GC–MS (EI, 70 eV): m/z (%): 342 (M+, 100), 279 (5), 264 (6),
249 (3), 233 (2), 215 (2), 171 (4), 124 (1), 91 (2), 65 (1), 39 (1);
HRMS (EI) calcd for C21H17F3O [M+]: 342.12260 found 342.122754.
4.4.2. 1-(40-Methylphenyl)-3-(400-ethylphenyl)-4-
trifluoromethylbenzene (5b)
Starting with 3c (0.08 g, 0.3 mmol), 2f (0.059 g, 1.3 equiv.),
Pd(PPh3)4 (0.017 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(4 mL), 5b was isolated as colorless oil (0.04 g, 40%). 1H NMR
4.5. Typical procedure for the synthesis of 4-bromo-3-
(300.13 MHz, CDCl3):
d
= 1.21 (t, J = 7.55 Hz, 3H, CH3), 2.31 (s, 3H,
(trifluoromethyl)biphenyls (7a–o)
CH3), 2.63 (q, J = 7.74 Hz, J = 15.30 Hz, 2H, –CH2–), 7.16–7.23 (m,
6H, ArH), 7.41–7.46 (m, 3H, ArH), 7.54–7.57 (m, 1H, ArH), 7.68 (d,
The reaction was carried out in a pressure tube. To a dioxane
suspension (5 mL) of the 1,4-dibromo-2-(trifluoromethyl)benzene
(6), Pd(PPh3)4 (3–5 mol%) and of the arylboronic acid (2) was added
an aqueous solution of K2CO3 (2 M, 1–2 mL). The mixture was
heated at the indicated temperature (70 8C) under Argon atmo-
sphere for the indicated period of time (8 h). The solution was
cooled to 20 8C, poured into H2O and CH2Cl2 (5 mL each), and the
organic and the aqueous layers were separated. The later was
extracted with CH2Cl2 (3 ꢂ 15 mL). The combined organic layers
were washed with H2O (3 ꢂ 10 mL), dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by chromatography (flash
silica gel, heptanes/EtOAc) to give 4-bromo-3-(trifluoromethyl)-
biphenyls (7a–o) (79–94%).
3J = 8.31 Hz, 1H, ArH); 13C NMR (62.89 MHz, CDCl3),
d
= 15.4 (CH3),
1
21.1 (CH3), 28.6 (–CH2–), 124.4 (CF3, q, JCF = 274.20 Hz), 125.3
(2CH), 126.6 (CH, q, 3JCF = 5.50 Hz), 127.1 (2CH), 127.3 (2CH), 128.5
4
(C), 128.9 (CH, q, JCF = 1.83 Hz), 129.6 (2CH), 126.9 (C, q,
2JCF = 30.21 Hz), 130.6 (CH), 136.5 (C), 137.3 (C), 141.9 (C, q,
3JCF = 1.83 Hz), 143.6 (C), 143.9 (C); 19F NMR (282.40 MHz, CDCl3):
˜
v
d
= ꢁ56.50 (ArCF3); IR (ATR, cmꢁ1):
¼ 3025 (w), 2928 (w), 2872
(w), 2731 (w), 2620 (w), 2431 (w), 2302 (w), 1905 (w), 1728 (w),
1665 (w), 1606 (m), 1514 (w), 1454 (w), 1384 (w), 1307 (s), 1265
(w), 1170 (m), 1112 (s), 1075 (m), 1029 (m), 1008 (w), 963 (w), 902
(w), 833 (w), 809 (s), 773 (w), 718 (w), 640 (w), 626 (w), 608 (w),
587 (w), 541 (w); GC–MS (EI, 70 eV): m/z (%): 340 (M+, 98), 325
(100), 305 (5), 270 (6), 241 (4), 189 (2), 162 (14), 127 (3), 105 (4), 91
(4), 65 (2), 51 (1), 39 (1); HRMS (EI) calcd for C22H19F3 [M+]:
340.14334 found 340.142981.
4.5.1. 40-Bromo-2-methyl-30-(trifluoromethyl)biphenyl (7a)
Starting from 6 (150 mg, 0.5 mmol), and 2a (68 mg, 0.5 mmol),
7a was obtained as a colorless oil (137 mg, 87%). 1H NMR
4.4.3. 1-(40-Methylphenyl)-3-(400-fluorophenyl)-4-
(300 MHz, 298 K, CDCl3): d = 2.17 (s, 3H, CH3), 7.09–7.26 (m, 5H,
trifluoromethylbenzene (5c)
H
Ar), 7.56 (d, 1H, J = 2.1 Hz, HAr), 7.66 (d, 1H, J = 8.1 Hz, HAr); 19F
Starting with 3c (0.12 g, 0.4 mmol), 2k (0.072 g, 1.3 equiv.),
Pd(PPh3)4 (0.023 g, 0.05 equiv.), 2 M K2CO3 (1 mL), 1,4-Dioxane
(4 mL), 5c was isolated as colorless oil (0.037 g, 25%). 1H NMR
NMR (282 MHz, 298 K, CDCl3):
CDCl3):
d
= ꢁ62.5; 13C NMR (75 MHz, 298 K,
d
= 20.3 (CH3), 118.4 (JC,F = 1.9 Hz, CAr), 122.9 (JC,F = 272 Hz,
CF3), 126.1, 128.2, 128.5 (JC,F = 5.3 Hz), 129.5 (CHAr), 129.9
(300.13 MHz, CDCl3):
d
= 2.33 (s, 3H, CH3), 6.99–7.07 (m, 2H, ArH),
(JC,F = 31.0 Hz, CAr), 130.6, 133.6, 134.7 (CHAr), 135.1, 139.2,
˜
7.17–7.29 (m, 4H, ArH), 7.43–7.46 (m, 3H, ArH), 7.59 (d,
3J = 8.31 Hz, 1H, ArH), 7.70 (d, 3J = 8.12 Hz, 1H, ArH); 13C NMR
141.4 (CAr); IR (neat):
v
¼ 3062, 3021, 2955, 1599 (w), 1470,
1399 (m), 1321 (s), 1248 (m), 1171, 1126, 1097, 1019 (s), 965, 906,

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
27
833 (m), 757, 724 (s), 659, 592, 555 (m) cmꢁ1. GC–MS (EI, 70 eV):
m/z (%) 314 (M+, 79Br, 99), 235 (17), 234 (11), 233 (10), 215 (22),
214 (12), 166 (68), 165 (70), 115 (8), 107 (8), 91 (7). HRMS (EI):
calcd. for C14H1079BrF3 [M]+: 313.991250; Found: 313.991255.
CAr), 122.8 (JC,F = 274 Hz, CF3), 127.2, 128.8 (JC,F = 5.4 Hz), 129.4
(JC,F = 31.7 Hz, CAr), 129.5, 130.2, 131.0 (CHAr), 132.3 (CAr), 133.9,
˜
134.6 (CHAr), 137.9, 138.7 (CAr); IR (neat):
v
¼ 3060, 1924, 1604,
1561 (w), 1464, 1389 (m), 1324 (s), 1283, 1242, 1173 (m), 1125 (s),
1074 (m), 1017 (s), 964 (w), 906, 831 (m), 753 (s), 696, 657 (m), 590
(w), 550 (m) cmꢁ1. GC–MS (EI, 70 eV): m/z (%) 334 (M+, 79Br + 35Cl,
76), 255 (9), 220 (23), 219 (15), 201 (8), 186 (8), 170 (7), 150 (9),
110 (7); HRMS (EI): calcd. for C13H779Br35ClF3 [M]+: 333.936630;
Found: 333.936584.
4.5.2. 4-Bromo-30,50-dimethyl-3-(trifluoromethyl)biphenyl (7b)
Starting from 6 (150 mg, 0.5 mmol), and 2e (75 mg, 0.5 mmol),
7b was obtained as a colorless heavy oil (137 mg, 83%). 1H NMR
(300 MHz, 298 K, CDCl3):
d = 2.30 (s, 6H, 2CH3), 6.98 (s, 1H, HAr),
7.09 (s, 1H, HAr), 7.49 (dd, 1H, J = 1.9, 8.3 Hz, HAr), 7.66 (d, 1H,
J = 8.3 Hz, HAr), 7.78 (d, 1H, J = 1.9 Hz, HAr); 19F NMR (282 MHz,
4.5.6. 4-Bromo-40-fluoro-3-(trifluoromethyl)biphenyl (7f)
Starting from 6 (150 mg, 0.5 mmol), and 2k (70 mg, 0.5 mmol),
7f was obtained as a yellowish heavy oil (128 mg, 80%). 1H NMR
298 K, CDCl3):
d
= ꢁ62.53; 13C NMR (75 MHz, 298 K, CDCl3):
d
= 21.4 (CH3), 118.4 (JC,F = 1.9 Hz, CAr), 122.9 (JC,F = 273 Hz, CF3),
124.8, 126.4 (JC,F = 5.4 Hz, CHAr), 129.9 (CHAr), 130.9 (JC,F = 31.0 Hz,
(300 MHz, 298 K, CDCl3): d = 7.04–7.10 (m, 2H, HAr), 7.41–7.46 (m,
C
Ar), 131.3, 135.1 (CHAr), 138.6, 138.7, 138.9, 140.9 (CAr); IR (neat,
2H, HAr), 7.67 (d, 1H, J = 8.2 Hz, HAr), 7.75 (d, 1H, J = 2.2 Hz, HAr); 19
F
cmꢁ1):
v
¼ 3022 (w), 2921 (m), 2853 (w), 1604 (m), 1568 (w),
NMR (282 MHz, 298 K, CDCl3):
(63 MHz, 298 K, CDCl3): d = 116.1 (JC,F = 21.7 Hz, CHAr), 118.7
d
= ꢁ62.61, ꢁ113.65; 13C NMR
˜
1468, 1391, 1334 (m), 1293 (s), 1251, 1207 (m), 1170 (m), 1128 (s),
1100, 1021 (m), 962, 892 (m), 825 (s), 760, 726 (w), 699, 659 (m),
597, 543 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 328 (M+, 79Br, 100),
315 (19), 313 (19), 249 (11), 234 (17), 233 (12), 214 (5), 184 (5),
180 (12), 179 (9), 178 (9), 165 (25), 152 (5); HRMS (EI): calcd. for
(JC,F = 1.8 Hz, CAr), 122.8 (JC,F = 274 Hz, CF3), 126.2 (JC,F = 5.4 Hz),
128.2 (JC,F = 8.2 Hz) (CHAr), 130.6 (JC,F = 31.2 Hz, CAr), 131.1 (CHAr),
134.8 (JC,F = 3.3 Hz, CAr) 135.4 (CHAr), 139.7, 163.0 (JC,F = 248.9 Hz)
˜
(CAr); IR (neat):
v
¼ 3045, 1892 (w), 1600, 1513 (m), 1473 (s), 1424,
C
15H1279BrF3 [M]+: 328.006900; Found: 328.006512.
1391 (m), 1325 (s), 1249 (m), 1173, 1099 (s), 1020 (m), 961 (w),
903 (m), 819 (s), 722, 659 (m), 612 (w), 570 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%) 318 (M+, 79Br, 100), 299 (10), 239 (17), 237 (8), 219
(35), 188 (6), 170 (28), 169 (9), 120 (8); HRMS (EI): calcd. for
4.5.3. 4-Bromo-40-ethyl-3-(trifluoromethyl)biphenyl (7c)
Starting from 6 (150 mg, 0.5 mmol), and 2f (75 mg, 0.5 mmol),
7c was obtained as a colorless oil (143 mg, 87%). 1H NMR
C
13H779BrF4 [M]+: 317.966180; Found: 317.966583.
(300 MHz, 298 K, CDCl3):
d = 1.18 (t, 3H, J = 7.5 Hz, CH3), 7.60 (q,
2H, J = 7.5 Hz, CH2), 7.20 (d, 2H, J = 8.3 Hz, HAr), 7.39 (d, 2H,
J = 8.3 Hz, HAr), 7.46 (dd, 1H, J = 8.2, 2.2 Hz, HAr), 7.64 (d, 1H,
J = 8.3 Hz, HAr), 7.78 (d, 1H, J = 2.2 Hz, HAr); 19F NMR (282 MHz,
4.5.7. 4-Bromo-3-(trifluoromethyl)biphenyl (7g)
Starting from 6 (150 mg, 0.5 mmol), and 2o (61 mg, 0.5 mmol),
7g was obtained as a colorless oil (123 mg, 82%). 1H NMR
298 K, CDCl3):
d
= ꢁ62.55; 13C NMR (63 MHz, 300 K, CDCl3):
(300 MHz, 298 K, CDCl3): d = 7.30–7.38 (m, 3H, HAr), 7.44–7.49 (m,
d
= 15.5 (CH3), 28.5 (CH2), 118.3 (JC,F = 1.8 Hz, CAr), 122.9
3H, HAr), 7.66 (d, 1H, J = 8.2 Hz, HAr), 7.78 (d, 1H, J = 8.2 Hz, HAr); 19
F
(JC,F = 273 Hz, CF3), 126.2 (JC,F = 5.4 Hz), 126.8, 128.6 (CHAr),
130.3 (JC,F = 31.5 Hz, CAr), 131.3, 135.2 (CHAr), 136.0, 140.6, 144.7
NMR (282 MHz, 298 K, CDCl3):
298 K, CDCl3): d = 118.7 (JC,F = 8.2 Hz, CAr), 122.9 (JC,F = 271 Hz,
d
= ꢁ62.5; 13C NMR (75 MHz,
˜
(CAr); IR (neat):
v
¼ 3027, 2965, 2873, 1602 (w), 1472, 1423 (m),
CF3), 126.4 (JC,F = 5.5 Hz), 126.9, 128.4, 129.1 (CHAr), 130.4
(JC,F = 32.3 Hz, CAr), 131.3. 135.3 (CHAr), 138.6, 140.7 (CAr); IR
1323 (s), 1251 (m), 1171 (m), 1128, 1100 (s), 1014 (m), 964 (w),
902 (m), 817 (s), 773, 716, 660 (m), 612 (w), 548 (m) cmꢁ1; GC–MS
(EI, 70 eV): m/z (%) 328 (M+, 79Br, 72), 316 (15), 315 (100), 314 (16),
313 (99), 249 (8), 234 (13), 233 (9), 183 (8), 178 (6), 165 (28);
HRMS (EI): calcd. for C15H1279BrF3 [M]+: 328.006900; Found:
328.006104.
˜
(neat):
v
¼ 3064, 3033, 1603 (w), 1470, 1401 (m), 1322 (s), 1251
(m), 1171, 1125, 1100, 1017 (s), 964, 898, 830 (m), 757, 694 (s), 617
(w), 545 (m) cmꢁ1. GC–MS (EI, 70 eV): m/z (%) 300 (M+, 79Br, 100),
221 (13), 219 (7), 201 (29), 170 (5), 152 (25), 151 (10), 150 (9), 111
(8); HRMS (EI): calcd. for C13H879BrF3 [M]+: 299.975600; Found:
299.975571.
4.5.4. 40-Bromo-2,3,4-trimethoxy-30-(trifluoromethyl)biphenyl (7d)
Starting from 6 (150 mg, 0.5 mmol), and 2i (106 mg, 0.5 mmol),
7d was obtained as a colorless heavy oil (160 mg, 82%). 1H NMR
4.5.8. 4-Bromo-30-chloro-3-(trifluoromethyl)biphenyl (7h)
Starting from 6 (150 mg, 0.5 mmol), and 2p (78 mg, 0.5 mmol),
7h was obtained as a colorless oil (144 mg, 86%). 1H NMR
(300 MHz, 298 K, CDCl3):
d = 3.63, 3.82, 3.84 (s, 9H, 3 OCH3), 6.67
(d, 1H, J = 8.7 Hz, HAr), 6.93 (d, 1H, J = 8.7 Hz, HAr), 7.45 (dd, 1H,
J = 8.3, 2.1 Hz, HAr), 7.63 (d, 1H, J = 8.3 Hz, HAr), 7.75 (d, 1H,
(300 MHz, 298 K, CDCl3): d = 7.28–7.33 (m, 3H, HAr), 7.43–7.46 (m,
2H, HAr), 7.67 (d, 1H, J = 8.3 Hz, HAr), 7.75 (d, 1H, J = 2.2 Hz, HAr); 19
F
J = 2.1 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ62.51; 13
C
NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ62.64; 13C NMR (75 MHz,
NMR (75 MHz, 298 K, CDCl3):
d
= 56.0. 61.0, 61.1 (OCH3), 107.7
300 K, CDCl3): d = 119.5 (JC,F = 1.8 Hz, CAr), 122.8 (JC,F = 272 Hz,
(CHAr), 118.0 (JC,F = 1.9 Hz, CAr), 123.0 (JC,F = 272 Hz, CF3), 124.4
(CHAr), 125.9 (CAr), 128.4 (JC,F = 5.4 Hz, CHAr), 129.8 (JC,F = 30.7 Hz,
CF3), 125.1, 126.3 (JC,F = 5.4 Hz), 127.1, 128.4, 130.4 (CHAr), 130.6
(JC,F = 31.1 Hz, CAr), 131.2 (CHAr), 135.1 (CAr), 135.5 (CHAr), 139.2,
˜
C
˜
v
Ar), 133.5, 134.6 (CHAr), 137.7, 142.7, 151.2, 154.0 (CAr); IR (neat):
¼ 2936, 2837 (w), 1595, 1498, 1462, 1417, 1325, 1278, 1209,
140.4 (CAr); IR (neat):
v
¼ 3060, 1924, 1807, 1604, 1562 (w), 1464,
1398 (m), 1324 (s), 1242 (m), 1173, 1126 (s), 1074 (m), 1017 (s),
964, 906, 831 (m), 753 (s), 696, 657 (m), 590 (w), 550 (m) cmꢁ1
GC–MS (EI, 70 eV): m/z (%) 334 (M+, 79Br + 35Cl, 78), 255 (10), 220
(22), 219 (14), 201 (7), 186 (8), 170 (5), 169 (6), 150 (5); HRMS (EI):
calcd. for C13H779Br35ClF3 [M]+: 333.936630; Found: 333.936717.
1171 (m), 1128, 1082, 1008 (s), 927, 903, 884, 834, 794, 723, 664
(m), 586 (w), 529 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 390 (M+,
79Br, 100), 377 (9), 375 (9), 334 (14), 332 (14), 296 (25), 281 (22),
263 (22), 261 (22), 236 (10), 195 (5), 182 (11); HRMS (EI): calcd. for
;
C
16H14O379BrF3 [M]+: 390.007290; Found: 390.006929.
4.5.9. 4-Bromo-3-(trifluoromethyl)-30-vinylbiphenyl (7i)
4.5.5. 40-Bromo-2-chloro-30-(trifluoromethyl)biphenyl (7e)
Starting from 6 (150 mg, 0.5 mmol), and 2j (78 mg, 0.5 mmol),
7e was obtained as a yellowish heavy oil (141 mg, 84%). 1H NMR
Starting from 6 (150 mg, 0.5 mmol), and 2q (74 mg, 0.5 mmol),
7i was obtained as a colorless oil (137 mg, 84%). 1H NMR (300 MHz,
298 K, CDCl3):
d = 5.21 (d, 1H, J = 10.8 Hz, 55CH2), 5.71 (d, 1H,
(300 MHz, 298 K, CDCl3):
d
= 7.22–7.27 (m, 3H, HAr), 7.37–7.42 (m,
J = 17.5 Hz, 55CH2), 6.65 (dd, 1H, J = 17.5, 10.8 Hz, 55CH), 7.28–7.33
(m, 3H, HAr), 7.42–7.46 (m, 2H, HAr), 7.63 (d, 1H, J = 8.2 Hz, HAr),
7.76 (d, 1H, J = 2.1 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
2H, HAr), 7.67–7.69 (m, 2H, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ62.5; 13C NMR (63 MHz, 300 K, CDCl3):
d = 119.3 (JC,F = 1.9 Hz,

28
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
d
= ꢁ62.51; 13C NMR (63 MHz, 300 K, CDCl3):
d
= 114.8 (55CH2),
J = 8.2 Hz, HAr), 7.75 (d, 1H, J = 1.9 Hz, HAr); 19F NMR (282 MHz,
118.8 (JC,F = 1.8 Hz, CAr), 122.9 (JC,F = 274 Hz, CF3), 124.9, 126.0,
126.3, 126.4 (JC,F = 5.4 Hz), 129.3 (CHAr), 130.4 (JC,F = 31.2 Hz, CAr),
131.3, 135.3 (CHAr), 136.0 (55CH), 138.4, 138.9, 140.5 (CAr); IR
˜
298 K, CDCl3):
d
= ꢁ62.48; 13C NMR (75 MHz, 298 K, CDCl3):
d
= 55.7, 55.8 (OCH3), 112.7, 114.0, 116.4 (CHAr), 118.4
(JC,F = 1.8 Hz, CAr), 123.0 (JC,F = 274 Hz, CF3), 128.8 (JC,F = 5.4 Hz,
CHAr), 128.9, 129.7 (JC,F = 31.0 Hz, CAr), 133.9, 134.5 (CHAr), 137.9,
(neat):
v
¼ 3045, 2927, 1892 (w), 1600, 1513, 1473, 1424 (m), 1324
˜
(s), 1266, 1236, 1173 (m), 1126 (s), 1020 (m), 903, 843 (m), 819 (s),
722, 659, 570 (m) cmꢁ1 GC–MS (EI, 70 eV): m/z (%) 326 (M+, 79Br,
100), 247 (8), 246 (12), 227 (6), 225 (5), 178 (25), 176 (11), 152 (6),
152 (6); HRMS (EI): calcd. for C15H1079BrF3 [M]+: 325.991250;
Found: 325.990805.
150.5, 153.9 (CAr); IR (neat):
v
¼ 3067, 2995, 2937, 2832, 1586 (w),
1515, 1474, 1401, 1327, 1286 (m), 1245, 1166, 1097, 1015 (s), 969,
910, 855 (m), 812 (s), 762, 671, 620, 582, 531 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%) 360 (M+, 79Br, 99), 347 (12), 345 (12), 267 (15), 266
(95), 252 (5), 251 (33), 223 (18), 218 (6), 207 (5), 206 (6), 195 (12),
188 (8), 175 (8), 169 (11); HRMS (EI): calcd. for C15H12O279BrF3
[M]+: 359.996730; Found: 359.996175.
4.5.10. 4-Bromo-40-tert-butyl-3-(trifluoromethyl)biphenyl (7j)
Starting from 6 (150 mg, 0.5 mmol), and 2r (90 mg, 0.5 mmol),
7j was obtained as a yellowish heavy oil (158 mg, 88%). 1H NMR
(300 MHz, 298 K, CDCl3):
7.50 (dd, 1H, J = 2.1, 8.3 Hz, HAr), 7.67 (d, 1H, J = 8.2 Hz, HAr), 7.80 (d,
1H, J = 2.1 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
= ꢁ62.61;
13C NMR (75 MHz, 298 K, CDCl3):
= 31.2 ((CH3)3), 34.6 (C(CH3)3),
4.5.14. 40-Bromo-2,6-dimethoxy-30-(trifluoromethyl)biphenyl (7n)
Starting from 6 (150 mg, 0.5 mmol), and 2v (91 mg, 0.5 mmol),
7n was obtained as a colorless dense oil (157 mg, 87%). 1H NMR
d = 1.28 (s, 9H, (CH3)3), 7.42 (s, 4H, HAr),
d
(300 MHz, 298 K, CDCl3): d = 3.65 (s, 6H, 2 OCH3), 6.39–6.43 (m, 1H,
d
H
Ar), 7.20–7.30 (m, 4H, HAr), 7.62 (d, 1H, J = 8.2 Hz, HAr); 19F NMR
118.3 (JC,F = 1.9 Hz, CAr), 123.0 (JC,F = 272 Hz, CF3), 126.1, 126.3
(JC,F = 5.4 Hz), 126.6 (CHAr), 130.4 (JC,F = 31.7 Hz, CAr), 131.1, 135.2
(282 MHz, 298 K, CDCl3):
CDCl3): d = 55.8 (2 OCH3), 104.1 (CHAr), 117.9 (JC,F = 1.7 Hz, CAr),
d
= ꢁ62.35; 13C NMR (75 MHz, 298 K,
˜
(CHAr), 135.7, 140.6, 151.6 (CAr); IR (neat):
v
¼ 3034, 2961, 2868,
123.2 (JC,F = 275.1 Hz, CF3), 128.9, 129.5 (JC,F = 31.2 Hz, CAr), 129.7
(JC,F = 5.3 Hz), 129.8, 134.1, 135.7 (CHAr), 137.8, 157.9 (CAr); IR
1601 (w), 1473, 1418 (m), 1325 (s), 1251, 1172 (m), 1129, 1100 (s),
1021 (m), 962 (w), 902 (m), 818 (s), 743, 697, 659 (m), 603 (w), 566
(m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 356 (M+, 79Br, 28), 344 (18),
343 (98), 342 (19), 341 (100), 315 (20), 313 (20), 262 (10), 233 (7),
222 (8), 165 (7), 157 (8), 156 (9); HRMS (EI): calcd. for C17H1679BrF3
[M]+: 356.038200; Found: 356.038994.
˜
(neat):
v
¼ 3065, 2999, 2935, 2830, 1587 (w), 1517, 1475, 1402,
1325, 1288 (m), 1245, 1165, 1098, 1015 (s), 971, 912, 855 (m), 811
(s), 762, 671, 615, 581, 530 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%)
360 (M+, 79Br, 100), 343 (5), 341 (5), 267 (5), 266 (30), 265 (5), 252
(5), 251 (24), 250 (7), 237 (6), 236 (9), 223 (16), 207 (8), 206 (7), 195
(10), 175 (7), 169 (8); HRMS (EI): calcd. for C15H12O279BrF3 [M]+:
359.996730; Found: 359.995736.
4.5.11. 4-Bromo-40-chloro-3-(trifluoromethyl)biphenyl (7k)
Starting from 6 (150 mg, 0.5 mmol), and 2s (78 mg, 0.5 mmol),
7k was obtained as a white solid (139 mg, 83%), mp = 50–52 8C. 1H
4.5.15. 4-Bromo-30,40-dimethoxy-3-(trifluoromethyl)biphenyl (7o)
NMR (300 MHz, 298 K, CDCl3):
d
= 7.35–7.42 (m, 4H, HAr), 7.46 (dd,
Starting from
0.5 mmol), 7o was obtained as a colorless heavy oil (170 mg,
94%). 1H NMR (300 MHz, 298 K, CDCl3):
= 3.85, 3.87 (s, 6H, 2
6 (150 mg, 0.5 mmol), and 2w (91 mg,
1H, J = 2.0, 8.1 Hz, HAr), 7.69 (d, 1H, J = 8.1 Hz, HAr), 7.76 (d, 1H,
J = 2.0 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
NMR (75 MHz, 298 K, CDCl3):
d
= ꢁ62.61; 13
C
d
d
= 119.1 (JC,F = 1.9 Hz, CAr), 122.8
OCH3), 6.87 (d, 1H, J = 8.2 Hz, HAr), 6.96 (d, 1H, J = 2.1 Hz, HAr),
7.02 (dd, 1H, J = 2.1, 8.2 Hz, HAr), 7.45 (dd, 1H, J = 2.2, 8.3 Hz,
(JC,F = 272 Hz, CF3), 126.2 (JC,F = 5.4 Hz), 128.2, 129.3 (CHAr), 130.6
(JC,F = 31.0 Hz, CAr), 131.1 (CHAr), 134.6 (CAr) 135.5 (CHAr), 137.1,
H
Ar), 7.64 (d, 1H, J = 8.3 Hz, HAr), 7.75 (d, 1H, J = 2.2 Hz, HAr); 19F
139.5 (CAr); IR (neat):
v
¼ 3037, 2926, 1899, 1596 (w), 1470, 1417
NMR (282 MHz, 298 K, CDCl3):
298 K, CDCl3): d = 55.7, 55.8 (OCH3), 112.7, 114.0, 116.4 (CHAr),
d
= ꢁ62.48; 13C NMR (75 MHz,
˜
(m), 1324 (s), 1248, 1171 (m), 1127, 1094, 1010 (s), 961 (w), 903
(m), 812 (s), 746, 695, 658 (m), 597 (w), 544 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%) 334 (M+, 79Br + 35Cl, 76), 255 (11), 235 (8), 220 (18),
219 (16), 201 (8), 186 (9), 151 (6), 150 (5), 128 (7); HRMS (EI):
calcd. for C13H779Br35ClF3 [M]+: 333.936630; Found: 333.936462.
118.4 (JC,F = 1.8 Hz, CAr), 123.0 (JC,F = 274 Hz, CF3), 128.8
(JC,F = 5.4 Hz, CHAr), 128.9, 129.7 (JC,F = 31.0 Hz, CAr), 133.9,
˜
v
134.5 (CHAr), 137.9, 150.5, 153.9 (CAr); IR (neat):
¼ 3066,
2998, 2937, 2833, 1588 (w), 1516, 1474, 1400, 1328, 1289 (m),
1244, 1166, 1099, 1016 (s), 970, 911, 856 (m), 810 (s), 761, 670,
619, 583, 532 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 360 (M+,
79Br, 100), 347 (14), 345 (14), 319 (16), 317 (17), 281 (7), 239
(8), 238 (56), 236 (8), 220 (11), 219 (5), 207 (8), 195 (15), 175
(6), 169 (8); HRMS (EI): calcd. for C15H12O279BrF3 [M]+:
359.996730; Found: 359.996658.
4.5.12. 2-(4-Bromo-3-(trifluoromethyl)phenyl)naphthalene (7l)
Starting from 6 (150 mg, 0.5 mmol), and 2t (86 mg, 0.5 mmol),
7l was obtained as a white crystalline solid (139 mg, 79%),
mp = 206–208 8C. 1H NMR (300 MHz, 298 K, CDCl3):
(m, 2H, HAr), 7.54–7.59 (m, 2H, HAr), 7.67 (d, 1H, J = 8.3 Hz, HAr),
7.75–7.88 (m, 5H, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
d = 7.40–7.44
d
= ꢁ62.4; 13C NMR (63 MHz, 298 K, CDCl3):
d
= 118.8 (JC,F
4.6. Typical procedure for the synthesis of 1,4-diaryl-3-
=1.8 Hz, CAr), 123.0 (JC,F = 274 Hz, CF3), 124.7, 126.0, 126.5
(JC,F = 5.4 Hz), 126.6, 126.7, 127.7, 128.2, 128.9 (CHAr), 130.3,
130.8 (CAr), 131.5 (CHAr), 132.2 (JC,F = 34.4 Hz, CAr) 135.4 (CHAr),
˜
(trifluoromethyl)benzene (8a–m)
The reaction was carried out in a pressure tube. To a dioxane
suspension (5 mL) of the 1,4-dibromo-2-(trifluoromethyl)benzene
(6), Pd(PPh3)4 (3–5 mol%) and of the arylboronic acid (2) was added
an aqueous solution of K2CO3 (2 M, 1–2 mL). The mixture was
heated at the indicated temperature (90 8C) under Argon atmo-
sphere for the indicated period of time (8 h). The solution was
cooled to 20 8C, poured into H2O and CH2Cl2 (5 mL each), and the
organic and the aqueous layers were separated. The latter was
extracted with CH2Cl2 (3 ꢂ 15 mL). The combined organic layers
were washed with H2O (3 ꢂ 10 mL), dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by chromatography (flash
silica gel, heptanes/EtOAc) to give 1,4-diaryl-3-(trifluoromethyl)-
benzene (8a–m) (79–95%).
135.9, 140.6 (CAr); IR (neat):
v
¼ 3048, 2916, 1586 (w), 1479, 1433,
1382, 1301 (m), 1230 (w), 1158, 1091, 1017 (m), 969, 885 (w), 814
(m), 743, 689 (s), 617 (m), 541 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%) 350 (M+, 79Br, 100), 271 (13), 270 (9), 269 (9), 251 (12), 220 (5),
202 (27), 200 (9), 176 (6); HRMS (EI): calcd. for C17H1079BrF3 [M]+:
349.991250; Found: 349.990657.
4.5.13. 40-Bromo-2,5-dimethoxy-30-(trifluoromethyl)biphenyl (7m)
Starting from 6 (150 mg, 0.5 mmol), and 2u (91 mg, 0.5 mmol),
7 m was obtained as a slight yellowish dense oil (166 mg, 92%). 1H
NMR (300 MHz, 298 K, CDCl3):
6.79 (m, 3H, HAr), 7.43 (dd, 1H, J = 1.9, 8.2 Hz, HAr), 7.61 (d, 1H,
d = 3.65, 3.69 (s, 6H, 2 OCH3), 6.76–

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
29
4.6.1. 2-Trifluoromethyl-1,4-bis(2-methylphenyl)-benzene (8a)
Starting from (150 mg, 0.5 mmol), and 2a (170 mg,
1.25 mmol), 8a was obtained as a colorless heavy oil (139 mg,
85%). 1H NMR (300 MHz, 298 K, CDCl3):
= 2.02, 2.52 (s, 6H, 2 CH3),
(w), 1124 (s), 1088, 1048, 996 (m), 946 (w), 900 (m), 836 (s), 761,
701, 651, 580 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 355 (40), 354
(M+, 100), 339 (15), 319 (32), 283 (22), 270 (44), 269 (30), 255 (39),
253 (41), 252 (36), 239 (33), 215 (19), 177 (39), 169 (24), 162 (48);
HRMS (EI): calcd. for C23H21F3 [M]+: 354.158990; Found:
354.158570.
6
d
7.13–7.24 (m, 9H, HAr), 7.44 (m, 1H, HAr), 7.64 (d, 1H, J = 1.8 Hz,
H
Ar); 19F NMR (282 MHz, 298 K, CDCl3):
(75 MHz, 298 K, CDCl3):
d
= ꢁ59.05; 13C NMR
d
= 20.1, 20.4 (CH3), 124.0 (JC,F = 270 Hz,
CF3), 124.8, 126.7 (JC,F = 5.1 Hz), 127.9 (CHAr), 128.5 (JC,F = 30.9 Hz,
4.6.5. 2-Trifluoromethyl-1,4-bis(4-ethylphenyl)-benzene (8e)
C
Ar), 129.5, 129.6, 129.7, 130.6, 131.4, 131.9 (CHAr), 135.3, 136.1,
Starting from
1.25 mmol), 8e was obtained as a white heavy oil (154 mg,
87%). 1H NMR (300 MHz, 298 K, CDCl3):
= 1.20 (t, 6H, J = 7.6 Hz,
6 (150 mg, 0.5 mmol), and 2f (187 mg,
˜
v
138.7, 139.0, 140.2 (JC,F = 1.9 Hz), 141.1 (CAr); IR (neat):
¼ 3021,
2924 (w), 1477, 1404 (m), 1321 (s), 1288, 1244 (m), 1167, 1117 (s),
1068, 1026, 1006 (m), 943 (w), 907, 846 (m), 753, 723 (s), 663, 583,
543 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 327 (24), 326 (M+, 100),
311 (17), 285 (15), 271 (13), 270 (19), 258 (15), 257 (65), 242 (38),
241 (33), 239 (29), 215 (14), 165 (25); HRMS (EI): calcd. for
d
CH3), 2.61 (q, 4H, J = 7.6 Hz, CH2), 7.13–7.29 (m, 7H, HAr), 7.46 (d,
2H, J = 8.2 Hz, HAr), 7.64 (dd, 1H, J = 7.8, 1.6 Hz, HAr), 7.85 (d, 1H,
J = 1.6 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ56.72; 13
C
NMR (63 MHz, 300 K, CDCl3):
d = 15.4 (CH3), 28.6 (CH2), 124.2
C
21H17F3 [M]+: 326.127690; Found: 326.127240.
(JC,F = 275 Hz, CF3), 124.5 (JC,F = 5.4 Hz), 127.0, 127.3, 128.5, 128.9
(JC,F = 1.6 Hz), (CHAr), 129.0 (JC,F = 31.2 Hz, CAr), 129.5, 132.7 (CHAr),
136.9, 137.0, 139.9 (JC,F = 1.8 Hz), 140.2, 143.6, 144.2 (CAr); IR
˜
4.6.2. 2-Trifluoromethyl-1,4-bis(3-methylphenyl)-benzene (8b)
Starting from (150 mg, 0.5 mmol), and 2b (170 mg,
1.25 mmol), 8b was obtained as a yellowish heavy oil (140 mg,
86%). 1H NMR (300 MHz, 298 K, CDCl3):
= 2.32, 2.36 (s, 6H, 2 CH3),
6
(neat):
v
¼ 3024, 2964, 1905, 1796, 1613 (w), 1487, 1426 (m), 1323
(s), 1264 (m), 1166, 1114 (s), 1069, 1005 (m), 964 (w), 903 (m), 821
(s), 718, 667, 588 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 355 (25),
354 (M+, 100), 340 (18), 339 (78), 324 (13), 270 (14), 252 (11), 241
(9), 239 (22), 169 (14), 162 (32); HRMS (EI): calcd. for C23H21F3
[M]+: 354.195640; Found: 354.195231.
d
7.07–7.36 (m, 9H, HAr), 7.66 (dd, 1H, J = 7.9, 1.6 Hz, HAr), 7.86 (d, 1H,
J = 1.6 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
NMR (75 MHz, 299 K, CDCl3):
d
= ꢁ56.72; 13
C
d
= 21.4, 21.5 (CH3), 123.2 (CHAr),
123.6 (JC,F = 275 Hz, CF3), 123.7 (JC,F = 5.4 Hz), 125.0, 126.6, 126.8,
127.3, 127.7, 127.9, 128.2, 128.6 (JC,F = 1.6 Hz) (CHAr), 131.5
(JC,F = 29.7 Hz, CAr), 131.7 (CHAr), 136.3, 137.6, 138.4, 138.5,
˜
4.6.6. 2-Trifluoromethyl-1,4-bis(2,3-dimethoxyphenyl)-benzene (8f)
Starting from
1.25 mmol), 8f was obtained as a colorless heavy oil (182 mg,
87%). 1H NMR (300 MHz, 298 K, CDCl3):
= 3.55, 3.60, 3.84, 3.85 (s,
6 (150 mg, 0.5 mmol), and 2h (227 mg,
139.1 (JC,F = 1.8 Hz), 139.4 (CAr); IR (neat):
v
¼ 3030, 2921 (w),
1605, 1477 (m), 1393 (w), 1325, 1273, 1244, 1163 (m), 1118 (s),
1073, 1054, 1033 (m), 971 (w), 894, 840 (m), 779, 700 (s), 665, 609
(m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 327 (23), 326 (M+, 100), 305
(17), 291 (35), 271 (23), 270 (49), 257 (37), 242 (49), 241 (56), 239
(42), 215 (24), 165 (31), 163 (46); HRMS (EI): calcd. for C21H17F3
[M]+: 326.127690; Found: 326.127298.
d
12H, 4 OCH3), 6.79–7.10 (m, 6H, HAr), 7.29 (d, 1H, J = 7.9 Hz, HAr),
7.66 (dd, 1H, J = 7.9, 1.4 Hz, HAr), 7.87 (d, 1H, J = 1.4 Hz, HAr); 19F
NMR (282 MHz, 299 K, CDCl3):
298 K, CDCl3):
d
= ꢁ57.9; 13C NMR (75 MHz,
d
= 55.8, 55.9, 60.5, 60.7 (OCH3), 112.2, 112.3,
122.4, 122.9 (CHAr), 123.8 (JC,F = 275.1 Hz, CF3), 124.3, 126.8
(JC,F = 5.4 Hz) (CHAr), 128.6 (JC,F = 29.4 Hz, CAr), 131.6, 132.0
(CHAr), 133.7, 134.2, 135.8, 135.9, 137.5, 146.6, 152.5, 153.2
˜
4.6.3. 2-Trifluoromethyl-1,4-bis(4-methylphenyl)-benzene (8c)
Starting from
1.25 mmol), 8c was obtained as a heavy oil (139 mg, 85%). 1H
NMR (300 MHz, 298 K, CDCl3): = 2.34 (s, 6H, 2 CH3), 7.12–7.30 (m,
7H, HAr), 7.46 (d, 2H, J = 8.1 Hz, HAr), 7.65 (dd, 1H, J = 7.8, 1.5 Hz,
6
(150 mg, 0.5 mmol), and 2c (170 mg,
(CAr); IR (neat):
v
¼ 3075, 2935, 2835, 1679 (w), 1579 (m), 1511
(w), 1465 (s), 1402, 1328, 1300 (m), 1260 (s), 1166 (m), 1119 (s),
1060 (m), 1001 (s), 907, 841, 786, 744, 674, 592, 541 (m) cmꢁ1
d
;
GC–MS (EI, 70 eV): m/z (%) 419 (27), 418 (M+, 100), 388 (13), 369
(5), 368 (43), 363 (14), 353 (17), 252 (29), 325 (15), 304 (24), 209
(32); HRMS (EI): calcd. for C23H21O4F3 [M]+: 418.138650; Found:
418.137837.
H
d
Ar), 7.67 (d, 1H, J = 1.5 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
= ꢁ56.78; 13C NMR (63 MHz, 300 K, CDCl3):
d = 21.1, 21.2 (CH3),
124.2 (JC,F = 275 Hz, CF3), 124.5 (JC,F = 5.4 Hz), 126.9, 128.5 (CHAr),
128.7 (JC,F = 29.7 Hz, CAr), 128.8, 129.5, 129.7, 132.7 (CHAr), 136.6,
136.7, 137.3, 137.8, 139.9, 140.2 (JC,F = 1.9 Hz) (CAr); IR (neat):
˜
4.6.7. 2-Trifluoromethyl-1,4-bis(2,3,4-trimethoxyphenyl)-benzene
v
¼ 3024, 2964, 1913, 1613 (w), 1487, 1423, 1323, 1265 (m), 1168,
(8g)
1109 (s), 1068, 1004, 966, 902 (m), 811 (s), 757, 719, 666, 587 (m)
cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 327 (23), 326 (M+, 100), 305 (28),
291 (35), 271 (28), 270 (47), 257 (61), 256 (25), 242 (49), 241 (56),
239 (42), 215 (24), 207 (31), 200 (55), 165 (39), 163 (46), 152 (41),
135 (63), 121 (60), 119 (82), 105 (71), 91 (84), 69 (86); HRMS (EI):
calcd. for C21H17F3 [M]+: 326.127690; Found: 326.127367.
Starting from
1.25 mmol), 8g was obtained as
(218 mg, 91%), mp = 85–87 8C. 1H NMR (300 MHz, 298 K, CDCl3):
= 3.73, 3.79 (s, 6H, 2 OCH3), 3.94 (s, 9H, 3 OCH3), 3.97 (s, 3H,
6
(150 mg, 0.5 mmol), and 2i (265 mg,
a
white crystalline solid
d
OCH3), 6.72 (d, 1H, J = 8.6 Hz, HAr), 6.81 (d, 1H, J = 8.6 Hz, HAr),
6.95 (d, 1H, J = 8.5 Hz, HAr), 7.13 (d, 1H, J = 8.5 Hz, HAr), 7.36 (d,
1H, J = 7.9 Hz, HAr), 7.71 (dd, 1H, J = 7.9, 1.7 Hz, HAr), 7.91 (d, 1H,
4.6.4. 2-Trifluoromethyl-1,4-bis(3,5-dimethylphenyl)-benzene (8d)
J = 1.7 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
NMR (75 MHz, 298 K, CDCl3): d = 55.9, 56.0, 60.8, 60.9, 61.0, 61.1
d
= ꢁ56.78; 13
C
Starting from
1.25 mmol), 8d was obtained as
(154 mg, 87%), mp = 108–109 8C. 1H NMR (300 MHz, 298 K, CDCl3):
= 2.41, 2.43, 2.45, 2.46 (s, 12H, 4CH3), 7.03 (s, 2H, HAr), 7.08–7.10
6
(150 mg, 0.5 mmol), and 2e (187 mg,
a
white crystalline solid
(OCH3), 106.3, 107.6 (CHAr), 124.2 (JC,F = 273 Hz, CF3), 124.7,
125.0 (JC,F = 1.4 Hz) (CHAr), 126.1 (CAr), 126.6 (JC,F = 5.3 Hz, CHAr),
126.9, 128.9 (JC,F = 29.2 Hz, CAr), 131.5, 132.4 (CHAr), 135.3
(JC,F = 2.0 Hz), 137.4, 141.9, 142.6, 151.4, 151.5, 153.6, 151.7
˜
d
(m, 2H, HAr), 7.28–7.30 (m, 2H, HAr), 7.41 (d, 1H, J = 7.9 Hz, HAr),
7.77 (dd, 1H, J = 7.9, 1.8 Hz, HAr), 7.97 (d, 1H, J = 1.8 Hz, HAr); 19F
(CAr); IR (neat):
v
¼ 2936, 2837 (w), 1597 (m), 1555 (w), 1481,
NMR (282 MHz, 298 K, CDCl3):
298 K, CDCl3):
d
= ꢁ56.70; 13C NMR (75 MHz,
1412, 1325, 1287, 1208, 1165 (m), 1108, 1078, 1003 (s), 920, 866,
793, 727, 695, 655 (m), 570 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z (%)
479 (29), 478 (M+, 100), 448 (28), 428 (25), 420 (43), 413 (36),
412 (45), 397 (14), 349 (35), 239 (52), 224 (22), 167 (25), 146
(24), 110 (9); HRMS (EI): calcd. for C25H25O6F3 [M]+: 478.159770;
Found: 478.159508.
d
= 21.3, 21.4 (CH3), 124.2 (JC,F = 274 Hz, CF3), 124.7
(JC,F = 5.4 Hz), 125.0 (CHAr), 125.1 (CAr), 126.8 (JC,F = 1.5 Hz, CHAr),
128.6 (JC,F = 29.5 Hz, CAr), 129.2, 129.6, 132.5 (CHAr), 137.2, 138.6,
˜
139.5, 139.6, 140.2, 140.3, 140.5 (CAr); IR (neat):
v
¼ 3020, 2916
(w), 1601, 1505, 1454, 1376, 1335 (m), 1293 (s), 1249 (m), 1199

30
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
4.6.8. 2-Trifluoromethyl-1,4-bis(3-trifluoromethylphenyl)-benzene
56.1, 56.2 (OCH3), 111.7, 112.6, 113.8, 113.9, 116.6, 116.8
(JC,F = 1.3 Hz), 117.2 (CHAr), 124.2 (JC,F = 272.5 Hz, CF3), 127.1
(JC,F = 5.4 Hz, CHAr), 128.8 (JC,F = 29.5 Hz), 129.4, 129.8 (CAr),
131.8, 132.1 (CHAr), 135.9 (JC,F = 1.8 Hz), 137.7, 150.7, 151.1,
˜
(8h)
Starting from
1.25 mmol), 8h was obtained as a colorless heavy oil (178 mg,
82%). 1H NMR (300 MHz, 298 K, CDCl3):
= 7.37 (d, 1H, J = 5.3 Hz,
Ar), 7.48 (m, 2H, HAr), 7.55–7.62 (m, 4H, HAr), 7.72–7.75 (m, 2H,
6 (150 mg, 0.5 mmol), and 2m (237 mg,
d
152.9, 153.9 (CAr); IR (neat):
v
¼ 2934, 2835 (w), 1593 (m), 1551
H
(w), 1480, 1413, 1321, 1289, 1209, 1163 (m), 1105, 1077, 1001 (s),
925, 868, 792, 725, 697, 654 (m), 573 (w) cmꢁ1; GC–MS (EI, 70 eV):
m/z (%) 419 (25), 418 (M+, 100), 388 (18), 369 (7), 368 (46), 363
(17), 353 (37), 352 (45), 325 (28), 297 (13), 209 (31), 194 (20);
HRMS (EI): calcd. for C23H21O4F3 [M]+: 418.138650; Found:
418.139359.
HAr), 7.80 (s, 1H, HAr), 7.90 (d, J = 1.0 Hz, HAr); 19F NMR (283 MHz,
300 K, CDCl3):
CDCl3):
d
= ꢁ62.65, ꢁ56.91; 13C NMR (75 MHz, 298 K,
d
= 123.9 (JC,F = 274.5 Hz, CF3), 124.2 (JC,F = 275.2 Hz, CF3),
123.9 (JC,F = 4.4 Hz), 124.7 (JC,F = 4.5 Hz), 125.1 (JC,F = 5.4 Hz), 125.8
(JC,F = 1.9 Hz), (CHAr), 129.3 (JC,F = 29.6 Hz, CAr), 129.6, 130.0 (CHAr),
130.0 (JC,F = 19.2 Hz, CAr), 130.5 (CHAr), 131.5 (JC,F = 19.4 Hz, CAr),
132.2, 132.6, 132.7 (CHAr), 139.2, 139.8, 139.9, 140.0 (CAr); IR
˜
4.6.12. 2-Trifluoromethyl-1,4-bis(3,4-dimethoxyphenyl)-benzene
(neat):
v
¼ 3074, 3043 (w), 1481, 1431, 1398, 1332, 1313, 1245,
(8l)
1164 (m), 1115, 1068, 1044 (s), 1001, 896, 845 (m), 799 (s), 759,
699, 653, 593, 561 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 435 (23),
434 (M+, 100), 416 (12), 415 (27), 413 (15), 395 (23), 364 (13), 346
(24), 345 (47), 325 (19), 296 (25), 275 (14), 269 (24), 219 (18), 201
(16); HRMS (EI): calcd. for C21H11F9 [M]+: 434.071160; Found:
434.070626.
Starting from 6 (150 mg, 0.5 mmol), and 2w (227 mg,
1.25 mmol), 8l was obtained as a yellowish crystalline solid
(198 mg, 95%), mp = 110–112 8C. 1H NMR (300 MHz, 298 K, CDCl3):
d
= 3.80, 3.85, 3.86, 3.89 (s, 12H, 4 OCH3), 6.84–7.12 (m, 6H, HAr),
7.32 (d, 1H, J = 7.9 Hz, HAr), 7.65 (dd, 1H, J = 7.9, 1.8 Hz, HAr), 7.81 (d,
1H, J = 1.8 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
= ꢁ56.78;
13C NMR (63 MHz, 300 K, CDCl3):
= 55.8, 55.9, 56.1, 56.2 (OCH3),
d
d
4.6.9. 2-Trifluoromethyl-1,4-bis(4-methoxyphenyl)-benzene (8i)
110.2, 110.5, 111.6, 112.5 (JC,F = 1.6 Hz), 119.5, 121.3 (CHAr), 124.2
(JC,F = 275.2 Hz, CF3), 124.4 (JC,F = 5.3 Hz, CHAr), 128.8
(JC,F = 29.5 Hz, CAr), 129.4 (CHAr), 132.1, 132.4 (CAr), 132.7 (CHAr),
139.4 (JC,F = 1.8 Hz), 140.1, 148.1, 148.9, 149.2, 149.4 (CAr); IR
˜
Starting from
1.25 mmol), 8i was obtained as a heavy oil (167 mg, 93%). 1H
NMR (300 MHz, 298 K, CDCl3): = 3.77, 3.78 (s, 6H, 2 OCH3), 6.86
6 (150 mg, 0.5 mmol), and 2n (190 mg,
d
(d, 2H, J = 8.7 Hz, HAr), 6.93 (d, 2H, J = 8.7 Hz, HAr), 7.18–7.27 (m,
3H, HAr), 7.48 (d, 2H, J = 8.8 Hz, HAr), 7.62 (dd, 1H, J = 8.8, 1.6 Hz,
(neat):
v
¼ 2935, 2836 (w), 1596 (m), 1555 (w), 1482, 1413, 1322,
1285, 1205, 1160 (m), 1107, 1074, 1002 (s), 923, 865, 792, 726, 693,
651 (m), 571 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 419 (24), 418
(M+, 100), 403 (25), 375 (30), 360 (48), 335 (31), 324 (23), 249 (19),
220 (15), 209 (49); HRMS (EI): calcd. for C23H21O4F3 [M]+:
418.138650; Found: 418.138754.
H
d
Ar), 7.82 (d, 1H, J = 1.6 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
= ꢁ56.83; 13C NMR (75 MHz, 298 K, CDCl3):
d = 55.2, 55.4 (OCH3),
113.3, 114.5, 124.2 (JC,F = 4.5 Hz) (CHAr) 124.3 (JC,F = 275 Hz, CF3),
128.1, 129.2, 130.1 (JC,F = 1.4 Hz), (CHAr), 130.8 (JC,F = 30.9 Hz, CAr),
132.0 (CHAr), 132.8, 139.2, 139.3, 139.8 (JC,F = 1.9 Hz), 159.1, 159.7
˜
(CAr); IR (neat):
v
¼ 3028, 2922 (w), 1605, 1475 (m), 1395 (w),
4.6.13. 2-Trifluoromethyl-1,4-bis(3-methoxyphenyl)-benzene (8m)
1321, 1270, 1241, 1165 (m), 1118 (s), 1074, 1050, 1032 (m), 972
(w), 895, 839 (m), 778, 705 (s), 663, 607 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%) 359 (22), 358 (M+, 100), 344 (12), 243 (32), 315 (14),
300 (14), 271 (17), 251 (41), 207 (15), 202 (22), 179 (49), 157 (28);
HRMS (EI): calcd. for C21H17O2F3 [M]+: 358.117520; Found:
358.116616.
Starting from
1.25 mmol), 8m was obtained as a heavy oil (159 mg, 89%). 1H
NMR (300 MHz, 298 K, CDCl3): = 3.76, 3.81 (s, 6H, 2 OCH3), 6.84–
6 (150 mg, 0.5 mmol), and 2x (190 mg,
d
6.89 (m, 4H, HAr), 7.06–7.31 (m, 5H, HAr), 7.66–7.69 (dd, 1H, J = 8.0,
1.6 Hz, HAr), 7.86 (d, 1H, J = 1.6 Hz, HAr); 19F NMR (282 MHz, 298 K,
CDCl3):
d
= ꢁ56.84; 13C NMR (75 MHz, 298 K, CDCl3):
d = 55.2, 55.3
(OCH3), 112.9, 113.3, 113.5, 114.7, 119.6, 121.5 (CHAr), 123.1
4.6.10. 1,4-Diphenyl-3-(trifluoromethyl)-benzene (8j)
(JC,F = 273 Hz, CF3), 124.8 (JC,F = 5.3 Hz, CHAr), 128.7 (JC,F = 30.3 Hz,
Starting from
1.25 mmol), 8j was obtained as a colorless heavy oil (127 mg,
85%). 1H NMR (300 MHz, 298 K, CDCl3):
= 7.26–7.58 (m, 11H,
6
(150 mg, 0.5 mmol), and 2o (152 mg,
C
Ar), 128.8, 130.0, 132.4 (CHAr), 14.0, 140.4 (JC,F = 1.9 Hz), 140.8,
˜
v
140.9, 158.9, 160.1 (CAr); IR (neat):
(m), 1392 (w), 1324, 1272, 1243, 1161 (m), 1116 (s), 1073, 1055,
1034 (m), 972 (w), 894, 842 (m), 779, 702 (s), 664, 607 (m) cmꢁ1
GC–MS (EI, 70 eV): m/z (%) 359 (33), 358 (M+, 100), 339 (27), 328
(39), 315 (53), 285 (21), 272 (17), 271 (14), 265 (15), 251 (42), 245
(24), 233 (23), 202 (26), 179 (52); HRMS (EI): calcd. for C21H17O2F3
[M]+: 358.117520; Found: 358.117099.
¼ 3032, 2919 (w), 1603, 1477
d
H
Ar), 7.68 (dd, 1H, J = 1.6, 7.9 Hz, HAr), 7.87 (d, 1H, J = 1.6 Hz, HAr);
;
19F NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ56.77; 13C NMR (75 MHz,
298 K, CDCl3):
d = 124.2 (JC,F = 273.1 Hz, CF3), 124.8 (JC,F = 5.2 Hz),
127.1, 127.7, 128.8, 128.0, 128.9, 129.0 (CHAr), 129.3 (JC,F = 31.1 Hz,
C
Ar), 129.7, 132.6 (CHAr), 139.5, 139.6, 140.2 (JC,F = 1.9 Hz), 140.5
(CAr); IR (neat, cmꢁ1):
v
¼ 3346 (br.), 2973, 1581 (w), 1451, 1403,
˜
1320, 1243, 1172 (m), 1124, 1071, 1044 (s), 1006, 977, 903, 879,
857, 837 (m), 761, 691 (s), 665, 597, 530 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%) 299 (49, M + 1), 298 (M+, 100), 278 (7), 277 (16),
259 (7), 257 (12), 229 (5), 228 (15), 227 (8), 226 (13), 202 (8), 201
(14), 149 (5); HRMS (EI): calcd. for C19H13F3 [M]+: 298.096390;
Found: 298.096115.
4.7. Typical procedure for the synthesis of 1,4-diaryl-3-
(trifluoromethyl)benzene (9a–d)
The reaction was carried out in a pressure tube. To a dioxane
suspension (5 mL) of the 4-aryl-1-bromo-2-trifluoromethylben-
zenes (7), Pd(PPh3)4 (3–5 mol%) and of the arylboronic acid (2) was
added an aqueous solution of K2CO3 (2 M, 1–2 mL). The mixture
was heated at the indicated temperature (80 8C) under Argon
atmosphere for the indicated period of time (8 h). The solution was
cooled to 20 8C, poured into H2O and CH2Cl2 (5 mL each), and the
organic and the aqueous layers were separated. The later was
extracted with CH2Cl2 (3 ꢂ 15 mL). The combined organic layers
were washed with H2O (3 ꢂ 10 mL), dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by chromatography (flash
silica gel, heptanes/EtOAc) to give 1,4-diaryl-3-(trifluoromethyl)-
benzene (9a–d) (80–88%).
4.6.11. 2-Trifluoromethyl-1,4-bis(2,5-dimethoxyphenyl)-benzene
(8k)
Starting from
1.25 mmol), 8k was obtained as a slight yellowish dense oil
(165 mg, 79%). 1H NMR (300 MHz, 298 K, CDCl3):
= 3.61, 3.68,
6 (150 mg, 0.5 mmol), and 2u (227 mg,
d
3.70, 3.72 (s, 12H, 4 OCH3), 6.72–6.88 (m, 6H, HAr), 7.23 (d, 1H,
J = 7.9 Hz, HAr), 7.64 (d, 1H, J = 7.9 Hz, HAr), 7.64 (dd, 1H, J = 7.9,
1.3 Hz, HAr), 7.82 (d, 1H, J = 1.3 Hz, HAr); 19F NMR (282 MHz, 298 K,
CDCl3):
d
= ꢁ58.81; 13C NMR (75 MHz, 298 K, CDCl3):
d = 55.7, 55.8,

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
31
4.7.1. 1-(30,40-Dimethoxy)-phenyl-4-(400-ethyl)-phenyl-2-
trifluoromethylbenzene (9a)
(83 mg, 86%), mp = 154–156 8C. 1H NMR (300 MHz, 298 K, CDCl3):
= 2.28 (s, 6H, 2CH3), 3.86, 3.90 (s, 6H, 2 OCH3), 6.89–6.95 (m, 4H,
d
Starting from 7c (82 mg, 0.25 mmol), and 2w (45 mg,
0.25 mmol), 9a was obtained as a yellowish crystalline solid
(85 mg, 88%), mp = 185–186 8C. 1H NMR (300 MHz, 298 K, CDCl3):
HAr), 7.06 (d, 1H, J = 2.1 Hz, HAr), 7.12 (dd, 1H, J = 8.2, 2.1 Hz, HAr),
7.28 (d, 1H, J = 7.9 Hz, HAr), 7.63 (dd, 1H, J = 7.9, 1.8 Hz, HAr), 7.81 (d,
1H, J = 1.8 Hz, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
d
= ꢁ56.74;
d
= 1.21 (t, 3H, J = 7.6 Hz, CH3), 2.64 (q, 2H, J = 7.6 Hz, CH2), 3.81,
3.85 (s, 6H, 2 OCH3), 6.82–6.85 (m, 3H, HAr), 7.24 (d, 2H, J = 8.3 Hz,
Ar), 7.33 (dd, 1H, J = 7.9 Hz, HAr), 7.48 (d, 2H, J = 8.3 Hz, HAr), 7.66
13C NMR (75 MHz, 298 K, CDCl3):
d = 56.0. 61.0, 61.1 (OCH3), 107.7
(CHAr), 118.0 (JC,F = 1.9 Hz, CAr), 123.0 (JC,F = 272 Hz, CF3), 124.4
(CHAr), 125.9 (CAr), 128.4 (JC,F = 5.4 Hz, CHAr), 129.8 (JC,F = 30.7 Hz,
H
(dd, 1H, J = 7.9, 1.8 Hz, HAr), 7.85 (d, 1H, J = 1.8 Hz, HAr); 19F NMR
CAr), 133.5, 134.6 (CHAr), 137.7, 142.7, 151.2, 154.0 (CAr); IR (neat):
= ꢁ56.81; 13C NMR (75 MHz, 298 K,
v
¼ 3000, 2916, 2843 (w), 1600, 1520, 1465 (m), 1389 (w), 1331,
˜
(282 MHz, 298 K, CDCl3):
CDCl3):
d
d
= 15.5 (CH3), 28.5 (CH2), 55.9 (2 OCH3), 110.5, 112.6,
1293 (m), 1244, 1112, 1047 (s), 966, 899 (m), 837 (s), 763, 708, 658,
616, 574 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 387 (36), 386 (M+,
100), 371 (28), 367 (20), 343 (59), 303 (29), 285 (25), 283 (31), 259
(25), 239 (26), 216 (14), 215 (36), 193 (28), 185 (33), 164 (41);
HRMS (EI): calcd. for C23H21O2F3 [M]+: 386.148820; Found:
386.148991.
121.4 (CHAr), 124.2 (JC,F = 278 Hz, CF3), 124.6 (JC,F = 5.3 Hz), 127.0,
128.5 (CHAr), 128.6 (JC,F = 28.7 Hz, CAr), 129.5 (CHAr), 132.2 (CAr),
132.7 (CHAr) 136.8, 139.7, 140.3, 144.3. 148.1, 148.6 (CAr); IR
˜
(neat):
v
¼ 3062, 2966, 2869, 1604, 1551 (w), 1488, 1454, 1409,
1322, 1248, 1216, 1164 (m), 1115 (s), 1071 (m), 1024 (s), 969 (m),
933 (w), 904, 868 (m), 817 (s), 764, 719, 646, 609, 541 (m) cmꢁ1
;
GC–MS (EI, 70 eV): m/z (%) 387 (25), 386 (M+, 100), 371 (31), 343
(25), 313 (39), 303 (25), 285 (22), 275 (30), 259 (41), 215 (16), 186
(49), 164 (13), 144 (29); HRMS (EI): calcd. for C23H21O2F3 [M]+:
386.148820; Found: 386.148894.
4.8. General procedure for the synthesis of 11a–i
A 1,4-Dioxane solution (8 mL) of 10 (1.0 mmol), arylboronic
acid 2 (1.0 equiv.), K3PO4, and Pd(PPh3)4 (5 mol%) was heated at
75 8C for 4 h. After cooling to room temperature, H2O was added
and the reaction mixture was extracted with CH2Cl2. The organic
layer was dried (Na2SO4), filtered and concentrated in vacuo. The
residue was purified by column chromatography (pure n-heptane).
4.7.2. 1-(30,40-Dimethoxy)-phenyl-4-naphthyl-2-
trifluoromethylbenzene (9b)
Starting from 7l (88 mg, 0.25 mmol), and 2w (45 mg,
0.25 mmol), 9b was obtained as a yellowish crystalline solid
(87 mg, 85%), mp = 212–214 8C. 1H NMR (300 MHz, 298 K, CDCl3):
4.8.1. 4-Chloro-20-methyl-2-(trifluoromethyl)biphenyl (11a)
Starting from 10 (259 mg, 1.0 mmol), and 2a (136 mg, 1.0
equiv.), 11a was obtained as a slight yellowish dense oil (90 mg,
d
= 3.81, 3.84 (s, 6H, 2 OCH3), 6.82–6.86 (m, 3H, HAr), 7.36–7.45 (m,
3H, HAr), 7.67 (dd, 1H, J = 8.5, 1.8 Hz, HAr), 7.77–7.87 (m, 4H, HAr),
8.00 (s, 2H, HAr); 19F NMR (282 MHz, 298 K, CDCl3):
NMR (75 MHz, 298 K, CDCl3):
d
= ꢁ56.72; 13
C
33%). 1H NMR (300.13 MHz, CDCl3):
d = 1.94 (s, 3H, CH3), 7.01 (d,
d
= 55.9, 56.0 (OCH3), 110.4, 112.6,
3J = 7.93 Hz, 1H), 7.08–7.24 (m, 4H), 7.43 (dd, J = 8.12 Hz,
J = 2.26 Hz, 1H), 7.66 (d, J = 2.26 Hz, 1H): 13C NMR (62.89 MHz,
121.4 (CHAr), 122.8 (JC,F = 275.2 Hz, CF3), 125.0, 125.1, 126.0, 126.4,
126.6 (CHAr), 127.1, 127.3 (CAr), 127.7, 128.3 (CHAr), 128.5
(JC,F = 29.7 Hz, CAr), 128.8, 129.9 (CHAr), 132.1 (CAr), 132.9 (CHAr),
˜
CDCl3),
d = 20.0 (CH3), 123.1 (CF3, q, JCF = 274.20 Hz), 125.0 (CH),
126.3 (q, JCF = 5.49 Hz, CH), 127.2 (CH), 128.2 (CH), 129.7 (CH),
130.3 (C, q, JCF = 30.21 Hz), 131.4 (CH), 133.1 (CH), 135.9 (C), 137.7
(C), 139.2 (C, q, JCF = 2.29 Hz), 141.6 (C); 19F NMR (282.40 MHz,
133.6, 136.7, 140.0, 140.2, 148.2, 148.7 (CAr); IR (neat):
v
¼ 3052,
2954, 2834, 1602 (w), 1495, 1462, 1407 (m), 1369 (w), 1314 (m),
1244, 1217, 1164, 1118 (s), 1071 (m), 1022 (s), 952, 886, 857 (m),
811, 748 (s), 719, 644, 607, 553 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%) 409 (27), 408 (M+, 100), 393 (13), 365 (32), 350 (29), 326 (23),
325 (47), 322 (30), 305 (14), 297 (16), 296 (44), 253 (14), 252 (39),
204 (59), 163 (52), 162 (36); HRMS (EI): calcd. for C25H19O2F3 [M]+:
408.133170; Found: 408.133547.
CDCl3):
d
= ꢁ59.62 (ArCF3); IR (ATR, cmꢁ1): (= 3063 (s), 3021 (s),
2956 (s), 2925 (s), 2857 (s), 1915 (s), 1599 (s), 1566 (s), 1493 (s),
1476 (m), 1453 (s), 1405 (m), 1381 (s), 1303 (w), 1275 (s), 1246
(m), 1168 (w), 1125 (w), 1105 (s), 1063 (w), 1047 (s), 1005 (m), 986
(s), 963 (s), 943 (s), 889 (m), 866 (s), 833 (w), 797 (s), 762 (w), 727
(w), 675 (m), 654 (s), 624 (s), 601 (m), 567 (m), 553 (s), 533 (s); MS
(GC, 70 eV): m/z (%): 270 (M+, [35Cl], 100), 250 (6), 235 (18), 215
(33), 201 (17), 183 (4), 165 (58), 139 (2), 107 (3), 91 (5), 63 (3), 51
(2), 39 (1); HRMS (EI) calcd for C14H10ClF3 [M+]: 270.04176 found
270.041702.
4.7.3. 1-(40-Fluoro)-phenyl-4-(300,400-dimethoxy)-phenyl-2-
trifluoromethylbenzene (9c)
Starting from 7o (90 mg, 0.25 mmol), and 2k (35 mg,
0.25 mmol), 9c was obtained as a yellowish crystalline solid
(75 mg, 80%) mp = 79–81 8C. 1H NMR (300 MHz, 298 K, CDCl3):
4.8.2. 4-Chloro-40-methyl-2-(trifluoromethyl)biphenyl (11b)
Starting from 10 (259 mg, 1.0 mmol), and 2c (135 mg, 1.0
equiv.), 11b was obtained as a colorless dense oil (245 mg, 91%). 1H
d
= 3.94, 4.02 (s, 6H, 2 OCH3), 6.98–7.81 (m, 10H, HAr); 19F NMR
(282 MHz, 298 K, CDCl3):
300 K, CDCl3):
d
= ꢁ56.82, ꢁ114.69; 13C NMR (63 MHz,
d
= 55.8, 56.0 (OCH3), 110.2, 110.6, 114.7
NMR (300.13 MHz, CDCl3):
7.36–7.42 (m, 2H), 7.62 (d, J = 2.27 Hz, 1H); 13C NMR (62.89 MHz,
CDCl3), = 21.2 (CH3), 123.4 (CF3, q, JCF = 274.20 Hz), 126.4 (CH, q,
d = 2.30 (s, 3H, CH3), 7.06–7.17 (m, 4H),
(JC,F = 21.5 Hz), 119.6 (CHAr), 124.1 (JC,F = 274.5 Hz, CF3), 124.5
(JC,F = 5.4 Hz) 128.7 (JC,F = 8.2 Hz, CHAr), 128.3, 129.3 (JC,F = 30.2 Hz)
(CAr), 129.5 (CHAr), 130.7 (CAr), 132.6 (CHAr), 132.8, 140.6, 149.3,
˜
d
JCF = 5.49 Hz), 126.8 (CH), 128.7 (CH), 128.8 (CH, q, JCF = 1.37 Hz),
129.5 (CH), 130.0 (C, q, JCF = 30.67 Hz), 131.4 (CH), 133.3 (C), 133.6
(CH), 135.7 (C), 137.8 (C), 140.1 (C, q, JCF = 1.83 Hz). 19F NMR
˜
149.4, 162.3 (JC–F = 247.2) (CAr); IR (neat):
v
¼ 3063, 2969, 2845,
1602 (w), 1525, 1488, 1428, 1332, 1294 (m), 1244, 1171, 1109 (s),
1055, 1021 (m), 970, 925 (w), 837, 806 (s), 764, 724, 670, 648 (m),
595 (w), 537 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%) 377 (23), 376
(M+, 100), 361 (23), 333 (30), 293 (39), 290 (20), 269 (14), 233 (20),
221 (24), 220 (46), 188 (44); HRMS (EI): calcd. for C21H16O2F4 [M]+:
376.108090; Found: 376.107788.
(282.40 MHz, CDCl3):
d
= ꢁ57.30 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3025
(s), 2923 (s), 2856 (s), 2733 (s), 1905 (s), 1777 (s), 1657 (s), 1600 (s),
1562 (s), 1500 (s), 1479 (w), 1402 (m), 1302 (w), 1266 (s), 1251 (s),
1239 (s), 1214 (s), 1166 (w), 1123 (w), 1111 (s), 1062 (w), 1024 (s),
1005 (m), 963 (s), 945 (s), 889 (m), 834 (m), 814 (w), 801 (m), 755
(s), 726 (w), 698 (s), 664 (m), 643 (s), 629 (m), 617 (s), 581 (m), 549
(s), 530 (m); MS (GC, 70 eV): m/z (%): 270 (M+, [35Cl], 100), 249 (5),
235 (9), 215 (22), 201 (5), 183 (3), 165 (20), 134 (2), 115 (3), 91 (4),
75 (1), 63 (1); HRMS (EI) calcd for C14H10ClF3 [M+]: 270.04176
found 270.041731.
4.7.4. 1-(30,50-Dimethyl)-phenyl-4-(300,400-dimethoxy)-phenyl-2-
trifluoromethylbenzene (9d)
Starting from 7o (90 mg, 0.25 mmol), and 2e (38 mg,
0.25 mmol), 9d was obtained as a yellowish crystalline solid

32
I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
4.8.3. 40-Chloro-2,3,4-trimethoxy-20-(trifluoromethyl)biphenyl (11c)
Startingfrom10(259 mg,1.0 mmol), and2n(212 mg, 1.0equiv.),
11f was obtained as a slight yellowish solid (145 mg, 42%). 1H NMR
(300.13 MHz, CDCl3):
2H), 7.23–7.30 (m, 3H), 7.53 (dd, J = 8.30 Hz, J = 2.26 Hz, 1H), 7.74
(d, J = 2.26 Hz, 1H); 13C NMR (62.89 MHz, CDCl3),
= 55.2 (OCH3),
d = 3.88 (s, 3H, OCH3), 6.95 (d, J = 8.87 Hz,
d
(300.13 MHz, CDCl3):
d
= 3.59 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 3.83
113.3 (2CH), 123.3 (CF3, q, JCF = 274.20 Hz), 126.4 (CH, q,
JCF = 5.49 Hz), 130.01 (C, q, JCF = 30.21 Hz), 130.03 (CH, q,
JCF = 1.37 Hz), 130.9 (C), 131.3 (CH), 133.2 (C), 133.7 (2CH),
139.7 (C, q, JCF = 1.83 Hz), 159.4 (C); 19F NMR (282.40 MHz, CDCl3):
˜
(s, 3H, OCH3), 6.60 (d, 1H, J = 8.69 Hz), 6.76 (dd, J = 8.49 Hz,
J = 0.75 Hz, 1H), 7.17 (d, 1H, J = 8.30 Hz), 7.43 (dd, J = 8.30 Hz,
J = 2.26 Hz, 1H), 7.64 (d, 1H, J = 2.26 Hz). 13C NMR (62.89 MHz,
CDCl3),
d
= 55.95 (OCH3), 60.74 (OCH3), 60.86 (OCH3), 106.28 (CH),
d
= ꢁ57.43 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3078 (s), 3040 (s), 3020 (s),
123.36 (CF3, q, JCF = 274.65 Hz), 124.8 (CH), 126.3 (CH, q,
JCF = 5.49 Hz), 127.9 (C), 130.5 (C, q, JCF = 30.21 Hz), 131.1 (CH),
134.1 (CH), 134.6 (C), 135.8 (C), 141.9 (C), 151.2 (C), 153.9 (C). 19
2967 (m), 2939 (m), 2914 (s), 2842 (m), 1882 (m), 1634 (s), 1611
(w), 1578 (s), 1562 (s), 1516 (m), 1481 (w), 1465 (s), 1455 (s), 1443
(m), 1403 (m), 1351 (s), 1332 (s), 1301 (w), 1247 (w), 1178 (w),
1133 (s), 1105 (w), 1063 (w), 1034 (w), 1018 (s), 1000 (m), 967 (s),
951 (m), 934 (s), 886 (w), 843 (m), 834 (s), 822 (w), 809 (s), 795 (m),
764 (s), 755 (s), 726 (w), 698 (s), 662 (m), 636 (m),618 (s), 585 (w),
550 (m), 535 (w); MS (GC, 70 eV): m/z (%): 286 (M+, 100), 271 (11),
243 (3), 223 (6), 208 (21), 188 (18), 169 (2), 139 (4), 99 (1), 87 (1),
75 (1), 63 (1); HRMS (EI) calcd for C14H10ClF3O [M+]: 286.03668
found 286.036392.
F
NMR (282.40 MHz, DMSO-d6):
d
= ꢁ58.66 (ArCF3); IR (ATR, cmꢁ1):
˜
v
¼ 3069 (m), 2961 (s), 2939 (m), 2910 (s), 2837 (s), 1847 (s), 1596
(w), 1574 (s), 1567 (s), 1504 (s), 1482 (w), 1462 (w), 1445 (s), 1435
(m), 1415 (m), 1407 (m), 1306 (w), 1293 (s), 1270 (m), 1250 (m),
1235 (m), 1209 (m), 1173 (w), 1131 (s), 1115 (w), 1101 (s), 1085 (w),
1053 (w), 1014 (m), 998 (w), 974 (s), 923 (s), 914 (m), 882 (m), 845
(m), 813 (s), 799 (w), 788 (s), 756 (s), 743 (s), 726 (m), 704 (s), 689
(m), 673 (s),658 (s), 646 (s), 611 (m), 589 (s), 572 (s), 536 (m); MS
(GC, 70 eV): m/z (%): 346 (M+, 100), 333 (8), 331 (24), 296 (27), 262
(6), 247 (4), 217 (20), 182 (16), 162 (2), 132 (1), 69 (1), 53 (2); HRMS
(EI) calcd for C16H14ClF3O3 [M+]: 346.05781 found 346.058121.
4.8.7. 4-Chloro-2-(trifluoromethyl)biphenyl (11g)
Starting from 10 (259 mg, 1.0 mmol), and 2o (121 mg, 1.0
equiv.), 11g was obtained as a colorless dense oil (215 mg, 84%). 1H
NMR (300.13 MHz, CDCl3):
3H), 7.41–7.52 (m, 1H), 7.64 (d, J = 2.08 Hz, 1H); 13C NMR
(62.89 MHz, CDCl3), = 123.3 (CF3, q, JCF = 274.66 Hz), 126.3 (CH,
d = 7.17–7.21 (m, 3H), 7.29–7.35 (m,
4.8.4. 4-Chloro-40-fluoro-2-(trifluoromethyl)biphenyl (11d)
Starting from 10 (259 mg, 1.0 mmol), and 2k (139 mg, 1.0
equiv.), 11d was obtained as a colorless dense oil (200 mg, 73%). 1H
d
q, JCF = 5.49 Hz), 127.2 (CH), 127.9 (CH), 128.8 (CH), 128.9 (CH),
129.9 (C, q, JCF = 30.67 Hz), 131.4 (CH), 133.5 (CH), 136.1 (CH),
138.6 (C), 139.9 (C, q, JCF = 1.83 Hz), 141.3 (C). 19F NMR
˜
NMR (300.13 MHz, CDCl3):
(m, 3H, ArH), 7.56 (dd, J = 2.27, J = 8.68 Hz, 1H, ArH), 7.76 (d,
J = 2.08 Hz, 1H, ArH); 13C NMR (62.89 MHz, CDCl3),
= 114.9 (2CH,
d = 7.09–7.15 (m, 2H, ArH), 7.27–7.32
d
(282.40 MHz, CDCl3):
d
= ꢁ57.32 (ArCF3); IR (ATR, cmꢁ1):
v
¼
d, JCF = 21.52 Hz), 123.2 (CF3, q, JCF = 274.20 Hz), 126.4 (CH, q,
JCF = 5.95 Hz), 130.6 (2CH, qd, JCF = 1.83 Hz, JCF = 8.24 Hz), 130.1 (C,
q, JCF = 30.67 Hz), 131.4 (CH), 133.5 (CH), 133.7 (C), 138.8 (C, q,
JCF = 1.83 Hz), 134.4 (C, d, JCF = 3.20 Hz), 162.6 (CF, d,
3064 (s), 3030 (s), 2926 (s), 2854 (s), 1605 (s), 1565 (s), 1476 (m),
1444 (s), 1432 (s), 1405 (m), 1336 (s), 1302 (w), 1246 (m), 1168
(m), 1123 (w), 1074 (s), 1063 (w), 1036 (s), 1024 (s), 1008 (m), 998
(s), 965 (s), 917 (s), 890 (m), 830 (w), 768 (w), 746 (s), 737 (m), 725
(s), 699 (w), 684 (m), 655 (m), 615 (s), 609 (s), 596 (m), 550 (m),
532 (s); MS (GC, 70 eV): m/z (%):MS (GC, 70 eV): m/z (%): 256 (M+,
JCF = 247.24 Hz); 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ57.46
(ArCF3), ꢁ114.13 (ArF); IR (ATR, cmꢁ1):
¼ 3075 (w), 2856 (w),
˜
v
1777 (w), 1600 (m), 1479 (s), 1402 (m), 1302 (s), 1230 (m), 1123
(s), 1062 (s), 1007 (m), 940 (w), 891 (m), 825 (s), 809 (s), 762 (w),
727 (s), 664 (m), 617 (w), 580 (m), 534 (m); GC–MS (EI, 70 eV): m/z
(%): 274 (M+, 100), 219 (29), 200 (1), 188 (4), 170 (10), 109 (3), 99
(2), 75 (1); HRMS (EI) calcd for C13H7ClF4 [M+]: 274.01669 found
274.015125.
[
35Cl], 100), 235 (6), 219 (6), 201 (38), 181 (2), 170 (3), 152 (9), 125
(1), 100 (4), 85 (1), 75 (2), 51 (1); HRMS (EI) calcd for C13H8ClF3
[M+]: 256.02611 found 256.026429.
4.8.8. 40-tert-Butyl-4-chloro-2-(trifluoromethyl)biphenyl (11h)
Starting from 10 (259 mg, 1.0 mmol), and 2r (178 mg, 1.0
equiv.), 11h was obtained as a colorless dense oil (145 mg, 46%). 1H
4.8.5. 4-Chloro-2,30-bis(trifluoromethyl)biphenyl (11e)
NMR (300.13 MHz, CDCl3): d = 1.39 (s, 9H, 3CH3), 7.25 (d, J = 8.12,
Starting from 10 (259 mg, 1.0 mmol), and 2 m (189 mg, 1.0
equiv.), 11e was obtained as a colorless dense oil (225 mg, 69%). 1H
2H, ArH), 7.44 (d, J = 8.49, 2H, ArH), 7.54 (dd, J = 1.89, J = 8.12 Hz,
1H, ArH), 7.69–7.76 (m, 2H, ArH); 13C NMR (62.89 MHz, CDCl3),
NMR (300.13 MHz, CDCl3):
5H), 7.66 (d, J = 1.89 Hz, 1H); 13C NMR (62.89 MHz, CDCl3),
= 123.1 (CF3, q, JCF = 274.20 Hz), 123.9 (CF3, q, JCF = 272.40 Hz),
d
= 7.15–7.19 (m, 1H), 7.38–7.48 (m,
d = 31.3 (3CH3), 34.6 (C), 122.1 (CF3, q, JCF = 273.74 Hz), 124.8
(2CH), 126.3 (CH, q, JCF = 5.49 Hz), 128.5 (2CH, q, JCF = 1.83 Hz),
129.9 (C, q, JCF = 30.67 Hz), 131.3 (CH), 133.6 (CH), 133.7 (C), 135.6
d
124.8 (CH, q, JCF = 3.66 Hz), 125.7 (CH, q, JCF = 1.83 Hz), 126.5 (CH,
q, 5JCF = 5.49 Hz), 128.4 (CH), 130.1 (C, q, JCF = 30.67 Hz), 130.5 (C, q,
JCF = 32.50 Hz), 131.6 (CH), 132.2 (CH), 133.2 (CH), 134.3 (C), 138.1
(C, q, JCF = 1.83 Hz), 139.2 (C). 19F NMR (282.40 MHz, CDCl3):
˜
(2C), 150.8 (C); 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ57.30 (ArCF3);
IR (ATR, cmꢁ1):
v
¼ 3073 (w), 2963 (m), 1777 (w), 1600 (w), 1480
˜
(m), 1364 (w), 1302 (s), 1243 (w), 1169 (m), 1125 (s), 1061 (s),
1004 (m), 923 (w), 890 (m), 824 (s), 751 (w), 711 (m), 641 (w), 585
(s), 543 (m); GC–MS (EI, 70 eV): m/z (%): 312 (M+, 22), 297 (100),
269 (17), 217 (4), 201 (3), 134 (4), 41 (4); HRMS (EI) calcd for
d
= ꢁ62.71 (ArCF3), ꢁ57.39 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3076 (s),
2929 (s), 2855 (s), 1602 (s), 1567 (s), 1512 (s), 1499 (s), 1479 (m),
1433 (m), 1405 (m), 1331 (w), 1300 (w), 1277 (m), 1250 (w), 1165
(w), 1118 (w), 1094 (m), 1076 (m), 1063 (w), 1024 (w), 1002 (s),
984 (s), 962 (s), 893 (m), 847 (m), 834 (m), 803 (w), 753 (s), 734 (w),
704 (w), 695 (m), 667 (s), 653 (s), 648 (s), 619 (s), 592 (s), 547 (m),
532 (s); MS (GC, 70 eV): m/z (%): MS (GC, 70 eV): m/z (%): 324 (M+,
C
17H16ClF3 [M+]: 312.08871 found 312.088232.
4.8.9. 4-Chloro-30,40-dimethoxy-2-(trifluoromethyl)biphenyl (11i)
Starting from 10 (259 mg, 1.0 mmol), and 2w (182 mg, 1.0
equiv.), 11i was obtained as a slight yellowish solid (120 mg, 38%).
[
35Cl], 100), 305 (8), 285 (3), 269 (13), 255 (1), 235 (13), 219 (11),
1H NMR (300.13 MHz, CDCl3):
d = 3.80 (s, 3H, OCH3), 3.85 (s, 3H,
201 (4), 169 (2), 150 (1), 125 (1), 109 (1), 169 (2), 99 (1), 75 (1);
HRMS (EI) calcd for C14H7ClF6 [M+]: 324.01350 found 324.013094.
OCH3), 6.75–6.84 (m, 3H, ArH), 7.22 (d, J = 8.30 Hz, 1H), 7.43 (dd,
J = 8.30 Hz, J = 1.70 Hz, 1H), 7.64 (d, J = 2.26 Hz, 1H): 13C NMR
(62.89 MHz, CDCl3),
d = 55.8 (2OCH3), 110.5 (CH), 112.4 (q,
4.8.6. 4-Chloro-40-methoxy-2-(trifluoromethyl)biphenyl (11f)
Starting from 10 (259 mg, 1.0 mmol), and 2n (152 mg, 1.0
equiv.), 11f was obtained as a white solid (155 mg, 61%). 1H NMR
JCF = 1.83 Hz, CH), 121.3 (q, JCF = 1.83 Hz, CH), 123.3 (CF3, q,
JCF = 274.20 Hz), 126.3 (q, JCF = 5.49 Hz, CH), 129.9 (C, q,
JCF = 30.21 Hz), 131.1 (C), 131.3 (CH), 133.3 (C), 133.6 (CH),

I. Ali et al. / Journal of Fluorine Chemistry 145 (2013) 18–34
33
139.7 (q, JCF = 1.83 Hz, C), 148.2 (C), 148.8 (C). 19F NMR
IR (ATR, cmꢁ1):
v
¼ 3023 (w), 2734 (w), 1604 (m), 1394 (m), 1334
˜
(282.40 MHz, CDCl3):
d
= ꢁ57.37 (ArCF3); IR (ATR, cmꢁ1):
¼
(s), 1294 (s), 1171 (m), 1128 (s), 1033 (s), 950 (w), 892 (m), 826 (s),
701 (m), 541 (w); GC–MS (EI, 70 eV): m/z (%): 284 (M+, 100), 269
(24), 233 (10), 165 (14), 125 (1), 77 (1), 69 (1); HRMS (EI) calcd for
15H12ClF3 [M+]: 284.05741 found 284.056637.
˜
v
3075 (s), 3015 (s), 2996 (s), 2962 (s), 2938 (s), 2909 (s), 2867 (s),
2838 (s), 1831 (s), 1606 (m), 1583 (m), 1567 (s), 1517 (w), 1485
(w), 1465 (w), 1453 (s), 1441 (m), 1411 (w), 1328 (s), 1304 (w),
1265 (s), 1249 (w), 1214 (w), 1189 (s), 1171 (w), 1120 (w), 1068
(w), 1048 (w), 1025 (w), 975 (s), 917 (s), 905 (m), 886 (m), 850 (w),
815 (s), 805 (w), 771 (m), 751 (m), 724 (w), 692 (s), 671 (s), 641 (w),
604 (m), 581 (s),539 (m); MS (GC, 70 eV): m/z (%): 316 (M+, [35Cl],
100), 301 (11), 273 (8), 258 (1), 233 (17), 218 (15), 195 (10), 169 (6),
126 (1), 99 (1), 87 (1), 75 (1), 63 (1), 51 (1); HRMS (EI) calcd for
C
4.9.4. 40-tert-Butyl-4-chloro-3-(trifluoromethyl)biphenyl (13d)
Starting from 12 (259 mg, 1.0 mmol), and 2r (178 mg, 1.0
equiv.), 13d was obtained as a colorless dense oil (270 mg, 87%). 1H
NMR (300.13 MHz, CDCl3):
7.47 (d, J = 8.31, 1H, ArH), 7.59 (dd, J = 1.89, J = 8.31 Hz, 1H, ArH),
7.81 (d, J = 2.08 Hz, 1H); 13C NMR (62.89 MHz, CDCl3),
= 31.2
d = 1.29 (s, 9H, 3CH3), 7.42 (s, 4H, ArH),
C
15H12ClF3O2 [M+]: 316.0427 found 316.047470.
d
(3CH3), 34.6 (C), 122.9 (CF3, q, JCF = 273.29 Hz), 125.9 (CH, q,
JCF = 5.49 Hz), 126.1 (2CH), 126.7 (2CH), 128.7 (C, q, JCF = 31.13 Hz),
130.8 (C, q, JCF = 1.83 Hz), 131.0 (CH), 131.8 (CH), 135.7 (C), 140.0
4.9. General procedure for synthesis of 13a–e
A 1,4-dioxane solution (8 mL) of 1 (1.0 mmol), arylboronic acid
2 (1.0 equiv.), K3PO4, and Pd(PPh3)4 (5 mol%) was heated at 70 8C
for 5 h. After cooling to room temperature, H2O was added and the
reaction mixture was extracted with CH2Cl2. The organic layer was
dried (Na2SO4), filtered and concentrated in vacuo. The residue was
purified by column chromatography (pure n-heptane).
(C), 151.6 (C); 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ62.57 (ArCF3); IR
(ATR, cmꢁ1):
¼ 3034 (w), 2962 (m), 1787 (w), 1579 (w), 1477
˜
v
(m), 1364 (w), 1325 (s), 1250 (m), 1174 (m), 1131 (s), 1111 (s),
1033 (s), 962 (w), 903 (m), 819 (s), 744 (m), 664 (m), 615 (w), 563
(w), 536 (m); GC–MS (EI, 70 eV): m/z (%): 312 (M+, 26), 297 (100),
269 (21), 217 (1), 201 (2), 135 (6), 41 (4); HRMS (EI) calcd for
C
17H16ClF3 [M+]: 312.08871 found 312.088893.
4.9.1. 40-Chloro-2-methyl-30-(trifluoromethyl)biphenyl (13a)
Starting from 12 (259 mg, 1.0 mmol), and 2a (135 mg, 1.0
equiv.), 13a was obtained as a colorless dense oil (260 mg, 96%). 1H
4.9.5. 40-Bromo-4-chloro-3-(trifluoromethyl)biphenyl (13e)
Starting from 12 (259 mg, 1.0 mmol), and 2x (200 mg, 1.0
equiv.), 13e was obtained as a white solid (150 mg, 45%). 1H NMR
NMR (300.13 MHz, CDCl3):
d = 2.17 (s, 3H, CH3), 7.09–7.23 (m, 4H,
ArH), 7.34 (dd, J = 2.64 Hz, J = 8.12 Hz, 1H, ArH), 7.46 (d, J = 8.31 Hz,
1H, ArH), 7.57 (d, J = 2.08 Hz, 1H); 13C NMR (62.89 MHz, CDCl3),
(300.13 MHz, CDCl3):
ArH), 7.88 (d, J = 2.08 Hz, 1H); 13C NMR (62.89 MHz, CDCl3),
= 122.7 (C), 122.8 (CF3, q, JCF = 273.74 Hz), 125.9 (CH, q,
d = 7.43–7.50 (m, 2H, ArH), 7.57–7.69 (m, 4H,
d
= 20.3 (CH3), 122.9 (CF3, q, JCF = 273.29 Hz), 126.2 (CH), 128.1 (C,
d
q, JCF = 31.13 Hz), 128.2 (CH), 128.3 (CH, q, JCF = 5.49 Hz), 129.6
(CH), 130.7 (CH), 130.8 (C, q, JCF = 1.83 Hz), 131.2 (CH), 133.5 (CH),
135.2 (C), 139.3 (C), 140.9 (C). 19F NMR (282.40 MHz, CDCl3):
˜
JCF = 5.49 Hz), 128.6 (2CH), 128.9 (C, q, JCF = 31.59 Hz), 130.9
(CH), 131.6 (C, q, JCF = 1.37 Hz), 131.9 (CH), 132.3 (2CH), 137.5 (C),
138.9 (C). 19F NMR (282.40 MHz, CDCl3):
d
= ꢁ62.64 (ArCF3); IR
˜
v
d
= ꢁ62.51 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3063 (w), 2862 (w), 1607
(ATR, cmꢁ1):
¼ 3064 (w), 2853 (w), 1587 (w), 1474 (m), 1325 (s),
(w), 1474 (m), 1403 (m), 1322 (s), 1247 (m), 1128 (s), 1053 (w), 964
(w), 907 (m), 834 (m), 757 (s), 660 (m), 594 (w), 532 (w); GC–MS
(EI, 70 eV): m/z (%): 270 (M+, 100), 235 (22), 215 (12), 165 (49), 139
(2), 91 (2), 63 (1); HRMS (EI) calcd for C14H10ClF3 [M+]: 270.04176
found 270.041299.
1250 (m), 1114 (s), 1030 (m), 905 (m), 846 (w), 812 (s), 730 (w),
663 (m), 599 (w), 526 (w); GC–MS (EI, 70 eV): m/z (%): 334 (M+, 74),
220 (28), 170 (3), 150 (5), 100 (1), 85 (2), 50 (1); HRMS (EI) calcd for
C
13H7BrClF3 [M+]: 333.93663 found 333.936439.
Acknowledgements
4.9.2. 4-Chloro-40-methyl-3-(trifluoromethyl)biphenyl (13b)
Starting from 12 (259 mg, 1.0 mmol), and 2c (135 mg, 1.0
equiv.), 13b was obtained as a colorless dense oil (265 mg, 98%). 1H
Financial support by the BMBF (REMEDIS Verbundprojekt), by
the DAAD (scholarship for I. U.), by the State of Pakistan (HEC
scholarships for I. A., M. N. and I. M.), by the Friedrich-Harms-
Stiftung (scholarship for A. A.) and by the State of Mecklenburg-
Vorpommern of Rostock (scholarships for I. M., M. N. and A. A.) is
gratefully acknowledged. The work was also supported by the
NMR (300.13 MHz, CDCl3): d = 2.33 (s, 3H, CH3), 7.19 (d, J = 8.31 Hz,
2H, ArH), 7.38 (d, J = 8.12 Hz, 2H, ArH), 7.46 (d, J = 8.49 Hz, 1H,
ArH), 7.57 (dd, J = 2.27 Hz, J = 8.31 Hz, 1H, ArH), 7.79 (d, J = 2.27 Hz,
1H); 13C NMR (62.89 MHz, CDCl3),
d = 21.1 (CH3), 123.0 (CF3, q,
JCF = 273.29 Hz), 125.8 (CH, q, JCF = 5.49 Hz), 126.8 (2CH), 128.7 (C,
q, JCF = 31.13 Hz), 129.8 (2CH), 130.8 (C, q, JCF = 1.83 Hz), 130.9
(CH), 131.7 (CH), 135.7 (C), 138.4 (CH), 140.1 (C). 19F NMR
˜
´
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.
(282.40 MHz, CDCl3):
d
= ꢁ62.56 (ArCF3); IR (ATR, cmꢁ1):
v
¼ 3030
(w), 2865 (w), 2607 (w), 1478 (m), 1396 (w), 1327 (s), 1174 (m),
1136 (s), 1033 (m), 903 (w), 809 (s), 728 (w), 665 (m), 547 (w); GC–
MS (EI, 70 eV): m/z (%): 270 (M+, 100), 235 (13), 215 (4), 165 (28),
135 (1), 91 (1), 63 (1); HRMS (EI) calcd for C14H10ClF3 [M+]:
270.04176 found 270.041748.
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