Palladium-catalyzed direct arylation of polyfluoroarene and facile synthesis of liquid crystal compounds

Article abstract of DOI:10.1002/aoc.3106

A convenient approach has been developed to prepare polyfluorobiphenyl by Pd(OAc)₂/PCy₃-catalyzed direct arylation of polyfluoroarenes with aromatic halides in the presence of Cs₂CO ₃ as base and toluene as solvent. In most cases, the desired arylated products of aromatic bromides were obtained in good to excellent yield at 80°C, and aryl chlorides also gave modest to good yields of arylated products at 110°C. According to this efficient C - C bondforming method, polyfluorobiphenyl liquid crystal compounds were prepared by Pd-catalyzed direct arylation reactions of polyfluoroarenes with long alkyl chain substituted aryl bromides in 62-96% yield. Copyright

Full text of DOI:10.1002/aoc.3106

Full Paper
Received: 25 September 2013
Revised: 31 October 2013
Accepted: 6 November 2013
Published online in Wiley Online Library: 21 January 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3106
Palladium-catalyzed direct arylation of
polyfluoroarene and facile synthesis of liquid
crystal compounds
Xiaowei Maa,b, Yan Liub, Ping Liub*, Jianwei Xieb, Bin Daib* and Zhiyong Liub
A convenient approach has been developed to prepare polyfluorobiphenyl by Pd(OAc)2/PCy3-catalyzed direct arylation of
polyfluoroarenes with aromatic halides in the presence of Cs2CO3 as base and toluene as solvent. In most cases, the desired
arylated products of aromatic bromides were obtained in good to excellent yield at 80°C, and aryl chlorides also gave modest
to good yields of arylated products at 110°C. According to this efficient C―C bondforming method, polyfluorobiphenyl liquid
crystal compounds were prepared by Pd-catalyzed direct arylation reactions of polyfluoroarenes with long alkyl chain
substituted aryl bromides in 62–96% yield. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: palladium; arylation; polyfluoroarenes; C―H activation; liquid crystal compounds
spectra were recorded at room temperature on a Varian Inova-400
spectrometer in CDCl3, with tetramethylsilane as an internal
Introduction
Polyfluorobiphenyl derivatives represent an important structural
motif frequently found in medicinal chemistry,[1] electron trans-
port devices,[2] organic light-emitting diodes,[3] sensitizers for
the photo-splitting of water[4] and liquid crystals.[5] Among the
myriad methods available for constructing polyfluorobiphenyl
compounds, transition-metal catalyzed cross-coupling reaction
of aryl metals reagent with aryl halide is one of the most
commonly used approaches,[6] but classical methods have an
intrinsic limitation in terms of atom and step economy
(Scheme 1).[7] In this context, direct arylation of aryl halide via
C―H functionalization of arene, which would avoid the use of a
arylmetallic intermediate, would be an attractive alternative to
the aforementioned traditional methods.[8] Recently, some signif-
icant progress has been made in the transition-metal catalyzed
direct C―H activation of polyfluoroarenes with arylhalides.[9–11]
For example, Fagnou et al. first proposed that Pd(OAc)2/
PtBu2Me-HBF4 or S-Phos catalyzed the direct arylation of
polyfluoroarenes with aryl halides.[9] Daugulis et al. reported
CuI-catalyzed arylation of polyfluoroarene C―H bonds with aryl
bromides or aryl iodides.[10] Furthermore, Zhang et al. illustrated
Pd-catalyzed cross-coupling of polyfluoroarenes with aryl iodides
in water.[11] Herein, we developed a new and simple catalysis
system that Pd-catalyzed direct arylation of aryl bromides and
even aryl chlorides via C―H functionalization of polyfluo-
roarenes, and which provided a concise and effective method
for the synthesis of polyfluorobiphenyl structures of interest
in liquid crystalline compounds.
standard and reported in ppm (δ). Electron ionization (EI)
mass spectra were measured on a high-resolution mass spec-
trometer (Thermo Finnigan Trace GC/MAT95 XP, America).
Toluene were dried over Na, distilled and stored under nitro-
gen. DMF, DMSO and 1,4-dioxane was distilled from calcium
hydride and degassed with N2. Column chromatography was
performed with silica gel (300–400 mesh) purchased from
Qingdao Haiyang Chemical Co. Ltd. Thin-layer chromatogra-
phy (TLC) was carried out with GF254 plates from the same
company. All other reagents were of analytical-grade quality
purchased commercially and used as received.
Typical procedure for Pd-catalyzed arylation of fluoroarene
with various aryl halides
The Schlenk tube (20 ml) equipped with a stir bar was charged
with Pd(OAc)2 (0.05 mmol, 10 mol%), PCy3 (0.1 mmol, 20 mol%),
and Cs2CO3 (1.2 equiv.). The reaction vessel was evacuated and
backfilled with nitrogen three times. Aryl halide (0.5 mmol),
fluoroarene (1.0 mmol) and solvent (1.0 ml) were added, and the
mixture was stirred at 80 or 110°C under N2 until the substrate
was completely consumed. After cooling to room temperature,
*
Correspondence to: Ping Liu and Bin Dai, School of Chemistry and Chemical
Engineering/Key Laboratory for Green Processing of Chemical Engineering of
Xinjiang Bingtuan, Shihezi University, Shihezi 832003, China. Email:
liuping1979112@aliyun.com; db_tea@shzu.edu.cn
Experimental
a School of Chemical Engineering and Technology, Tianjin University, Tianjin,
300072, China
Materials and instruments
b School of Chemistry and Chemical Engineering/Key Laboratory for Green
Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi Univer-
sity, Shihezi, 832003, China
All the reactions were carried out under N2 using magnetic
1
stirring unless otherwise noted. H NMR, 13C NMR and 19F NMR
Appl. Organometal. Chem. 2014, 28, 180–185
Copyright © 2014 John Wiley & Sons, Ltd.

Palladium-catalyzed direct arylation of polyfluoroarene
H13), 1.31–1.21 (m, 6H, H15 and H15′, H18, H19), 1.20–1.12 (m, 6H,
H11 and H11′, H14 and H14′, H15 and H15′), 1.10–0.96 (m, 3H,
H16 and H17), 0.90–0.83 (m, 5H, H20 and H21). 13C NMR (100
MHz, CDCl3): δ 149.2 (C8), 144.2 (dm, J= 246.1 Hz, C3 and C3′),
140.2 (dm, J= 251.8 Hz, C1), 137.8 (dm, J = 231.0 Hz, C2 and C2′),
130.0 (C5), 127.2 (C7 and C7′), 123.7 (C6 and C6′), 116.1 (td,
J = 17.2, J = 4.2 Hz, C4), 44.6 (C9), 43.5 (C12), 43.0 (C13), 38.0 (C17),
37.5 (C19), 34.5 (C10 and C10′), 33.7 (C14 and C14′), 32.3 (C16),
30.4 (C18), 30.2 (C15 and C15′), 26.7 (C11 and C11′), 22.7 (C20),
14.1(C21). 19F NMR (376 MHz, CDCl3): δ À143.41 (dd, J = 23.1, 8.2
Hz, 2F, F2 and F2′), À156.24 (t, J = 21.0 Hz, 1F, F1), À162.51 (td,
J = 22.9, 8.2 Hz, 2F, F3 and F3′). HRMS calcd for C29H35F5 (M+)
478.2651; found: 478.2653. Anal. Calcd for C29H35F5: C, 72.78; H,
7.37. Found: C, 72.54; H: 7.57.
Scheme 1. Strategies toward synthesis of polyfluorobiphenyl derivatives.
the mixture was quenched with water and extracted with EtOAc
(3× 10 ml). The combined EtOAc extracts were dried with
anhydrous Na2SO4, filtrated and the solvent was removed
under reduced pressure. The residue was purified by flash
column chromatography on silica gel with petroleum ether
(PE) or PE/EtOAc as the eluent to obtain the desired products.
(Characterization data of compounds 3a–3p can be found in
the supporting information).
2,3,5,6-Tetrafluoro-4′-(4-propylcyclohexyl)-1,1′-biphenyl (4d)
Yield 80%, white solid, m.p. 85–87°C. 1H NMR (400 MHz, CDCl3): δ
7.40–7.32 (m, 4H, Ar―H), 7.08–7.00 (m, 1H, ArF―H), 2.53 (tt,
J = 12.3, 3.2 Hz, 1H, H9), 2.02–1.81 (m, 4H, H10 and H10′),
1.54–1.44 and 1.11–1.02 (m, 4H, H11 and H11′), 1.43–1.27 (m, 3H,
H12 and H13), 1.27– 1.17 (m, 2H, ―CH2CH2CH3), 0.91 (t, J = 7.2
Hz, 3H, ―CH3). 13C NMR (100 MHz, CDCl3): δ 149.1 (C8), 146.2
(dm, J = 258.3 Hz, C3 and C3′), 143.9 (dm, J = 255.8 Hz, C2 and
C2′), 130.0 (t, J = 2.0 Hz, C5), 127.1 (C7 and C7′), 124.8 (t, J = 2.4
Hz, C6 and C6′), 121.6(C4), 104.5 (t, J = 22.7 Hz, C1), 44.5 (C9), 39.7
(C13), 37.0 (C10 and C10′), 34.2 (C11 and C11′), 33.5 (C12), 20.0
2,3,4,5,6-Pentafluoro-4′-(4-propylcyclohexyl)-1,1′-biphenyl (4a)
1
Yield 88%, 162.0 mg, white solid, m.p. 106–107°C. H NMR (400
MHz, CDCl3) δ 7.37–7.30 (m, 4H, Ar―H), 2.53 (tt, J = 12.3, 3.2 Hz,
1H, H9 ), 2.02–1.81 (m, 4H, H10 and H10′), 1.54–1.44 and
1.11–1.02 (m, 4H, H11 and H11′), 1.41–1.27 (m, 3H, H12 and
H13), 1.27–1.17 (m, 2H, ―CH2CH2CH3), 0.91 (t, J = 7.2 Hz, 3H,
(C14), 14.1(C15). 19F NMR (376 MHz, CDCl3):
δ
À139.42
(ddd, J = 22.5, 12.7, 9.8 Hz, 2F, F2 and F2′), À144.1 (ddd, J = 21.4,
12.8, 7.5 Hz, 2F, F3 and F3′). HRMS calcd for C21H22F4 (M+)
350.1658; found: 350.1657. Anal. Calcd for C21H22F4: C, 71.98; H,
6.33. Found: C, 71.71; H: 6.61.
―CH3). 13C NMR (100 MHz, CDCl3):
δ 149.2 (C8), 144.2
(dm, J = 249.0 Hz, C3 and C3′), 140.1 (dm, J = 256.5 Hz, C1), 137.9
(dm, J = 264.5 Hz, C2 and C2′), 130.0 (C5), 127.2 (C7 and C7′),
123.6 (C6 and C6′), 115.9 (td, J = 17.4, 3.7 Hz, C4), 44.4 (C9), 39.7
(C13), 37.0 (C10 and C10′), 34.2 (C11 and C11′), 33.5 (C12), 20.0
(C14), 14.4 (C15). 19F NMR (376 MHz, CDCl3): δ À143.41 (dd, J= 23.1,
8.2 Hz, 2F, F2 and F2′), À156.23 (t, J= 21.0 Hz, 1F, F1), À162.50 (td,
J= 22.9, 8.2 Hz, 2F, F3 and F3′). HRMS calcd for C21H21F5 (M+):
368.1563; found: 368.1560. Anal. Calcd for C21H21F5: C, 68.47;
H, 5.75. Found: C, 68.25; H: 5.87.
2,3,5,6-Tetrafluoro-4′-(4-pentylcyclohexyl)-1,1′-biphenyl (4e)
1
Yield 78%, white solid, m.p. 89–91°C. H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3): δ 7.40–7.36 (m, 4H, Ar―H), 7.08–7.00
(m, 1H, ArF―H), 2.53 (tt, J = 12.4, 3.3 Hz, 1H, H9), 1.96–1.87 (m, 4H,
H10 and H10′), 1.54–1.44 and 1.12–1.02 (m, 4H, H11 and H11′),
1.35–1.22 (m, 9H, H12, H13, H14, H15 and H16), 0.90 (t, J = 7.0 Hz,
3H, ―CH3). 13C NMR (100 MHz, CDCl3): δ 149.0 (C8), 146.1 (dm,
J = 246.7 Hz, C3 and C3′), 143.9 (dm, J = 247.6 Hz, C2 and C2′),
130.0 (t, J = 2.0 Hz, C5), 127.1 (C7 and C7′), 124.8 (t, J = 2.0 Hz, C6
and C6′), 121.6 (C4), 104.5 (t, J = 22.7 Hz, C1), 44.5 (C9), 37.4 (C13),
37.3 (C10 and C10′), 34.2 (C11 and C11′), 33.6 (C12), 32.2 (C14),
26.7 (C15), 22.7 (C16), 14.1 (C17). 19F NMR (376 MHz, CDCl3): δ
À139.42 (ddd, J = 22.5, 12.7, 9.8 Hz, 2F, F2 and F2′), À144.1 (ddd,
J = 21.1, 12.8, 7.5 Hz, 2F, F3 and F3′). HRMS calcd for C23H26F4 (M+)
378.1968; found: 378.1965. Anal. Calcd for C23H26F4: C, 72.99; H,
6.92. Found: C, 72.70; H: 7.21.
2,3,4,5,6-Pentafluoro-4′-(4-pentylcyclohexyl)-1,1′-biphenyl (4b)
Yield 92%, white solid, m.p. 100–101°C. 1H NMR (400 MHz, CDCl3):
δ 7.36–7.30 (m, 4H, Ar―H), 2.53 (tt, J = 12.4, 3.3 Hz, 1H, H9), 2.01–
1.81 (m, 4H, H10 and H10′), 1.53–1.43 and 1.11–1.02 (m, 4H, H11
and H11′), 1.41–1.27 (m, 9H, H12, H13, H14, H15 and H16), 0.90
(t, J = 7.0 Hz, 3H, ―CH3). 13C NMR (100 MHz, CDCl3): δ 149.2
(C8), 144.3 (dm, J = 245.8 Hz, C3 and C3′), 140.0 (dm, J = 246.6
Hz, C1), 138.0 (dm, J = 251.5 Hz, C2 and C2′), 130.0 (C5), 127.2
(C7 and C7′), 123.7 (C6 and C6′), 116.0 (td, J = 17.6, 3.7 Hz, C4),
44.5 (C9), 37.4 (C13), 37.3 (C15), 34.2 (C10 and C10′), 33.6
(C11 and C11′), 32.2 (C12), 26.7 (C14), 22.8 (C16), 14.1 (C17). 19F
NMR (376 MHz, CDCl3): δ À143.41 (dd, J = 23.1, 8.2 Hz, 2F, F2
and F2′), -156.23 (t, J = 21.0 Hz, 1F, F1), À162.50 (dt, J = 22.9, 8.2
Hz, 2F, F3 and F3′). HRMS calcd for C23H25F5 (M+): 396.1876; found:
396.1879. Anal. Calcd for C23H25F5: C, 69.68; H, 6.36. Found: C, 69.45;
H: 6.63.
2,3,5,6-Tetrafluoro-4′-(4′-pentyl-[1,1′-bi(cyclohexan)]-4-yl)-1,1′-biphenyl (4f)
Yield 82%, white solid, m.p. 173–175°C. 1H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3): δ 7.39–7.31 (m, 4H, Ar―H), 7.08–7.00
(m, 1H, ArF―H), 2.51 (tt, J = 11.6, 3.1 Hz, 1H, H9), 1.97–1.93 (m, 2H,
H10 and H10′), 1.88–1.84 (m, 2H, H11 and H11′), 1.78–1.73 (m, 4H,
H10 and H10′, H14 and H14′ ), 1.54–1.43 (m, 2H, H12 and
H13), 1.33–1.20 (m, 6H, H15 and H15′, H18, H19), 1.20–1.13
(m, 6H, H11 and H11′, H14 and H14′, H15 and H15′), 1.13–0.97
(m, 3H, H16 and H17), 0.92–0.85 (m, 5H, H20 and ―CH3). 13C
NMR (100 MHz, CDCl3): δ 149.1 (C8), 146.1 (dm, J = 246.3 Hz, C3
and C3′), 143.9 (dm, J = 247.6 Hz, C2 and C2′), 130.0 (C5), 127.1
(C7 and C7′), 124.8 (C6 and C6′), 121.6 (t, J = 16.5 Hz, C4), 104.5
(t, J = 22.5 Hz, C1), 44.5 (C9), 43.4 (C12), 43.0 (C13), 38.0 (C17),
2,3,4,5,6-Pentafluoro-4′-(4′-pentyl-[1,1′-bi(cyclohexan)]-4-yl)-1,1′-biphenyl (4c)
Yield 96%, white solid, m.p. 141–142°C. 1H NMR (400 MHz, CDCl3):
δ 7.36–7.31 (m, 4H, Ar―H), 2.51 (tt, J= 11.6, 3.1 Hz, 1H, H9), 1.98–1.93
(m, 2H, H10 and H10′), 1.88–1.86 (m, 2H, H11 and H11′), 1.79–1.73
(m, 4H, H10 and H10′, H14 and H14′ ), 1.53–1.41 (m, 2H, H12 and
Appl. Organometal. Chem. 2014, 28, 180–185
Copyright © 2014 John Wiley & Sons, Ltd.
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X. Ma et al.
37.5 (C19), 34.5 (C10 and C10′), 33.7 (C14 and C14′), 32.3 (C16), 30.3
(C18), 30.2 (C15 and C15′), 26.7 (C11 and C11′), 22.8 (C20), 14.2
(C21). 19F NMR (376 MHz, CDCl3): δ À139.4 (ddd, J= 22.5, 12.7, 9.8
Hz, 2F, F2 and F2′), À144.1 (ddd, J= 21.1, 12.8, 7.5 Hz, 2F, F3 and
F3′). HRMS calcd for C29H36F4 (M+) 460.2751; found: 460.2748. Anal.
Calcd for C29H36F4: C, 75.62; H, 7.88. Found: C, 75.33; H: 8.08.
(C13), 37.0 (C10 and C10′), 34.2 (C11 and C11′), 33.5 (C12), 20.1
(C14), 14.4 (C15). 19F NMR (376 MHz, CDCl3): δ À118.22 (t, J = 10.1
Hz, 1F, F2), À134.01 (ddd, J = 21.4, 9.9, 5.1 Hz, 1F, F3),
À135.59 (d, J = 21.6 Hz, 1F, F1), À165.00 (tdd, J = 21.6, 10.9,
6.1 Hz, 1F, F4). HRMS calcd for C21H22F4 (M+) 350.1658; found:
350.1654. Anal. Calcd for C21H22F4: C, 71.98; H, 6.33. Found: C,
71.73; H: 6.57.
2,3,4,6-Tetrafluoro-4′-(4-propylcyclohexyl)-1,1′-biphenyl (4g)
2,3,4,6-Tetrafluoro-4′-(4-pentylcyclohexyl)-1,1′-biphenyl (4h)
Yield 71%, white solid, m.p. 71–72°C. 1H NMR (400 MHz, CDCl3): δ
7.36–7.26 (m, 4H, Ar―H), 6.89–6.82 (m, 1H, ArF―H), 2.52 (tt, J = 12.2,
3.3 Hz, 1H, H9 ), 1.96–1.86 (m, 4H, H10 and H10′), 1.53–1.44 and
1.12–1.01 (m, 4H, H11 and H11′), 1.41–1.27 (m, 3H, H12 and H13),
Yield 75%, white solid, m.p. 54–56°C. 1H NMR (400 MHz, CDCl3): δ
7.36–7.29 (m, 4H, Ar―H), 6.89–6.81 (m, 1H, ArF―H), 2.52 (tt, J = 12.4,
3.3 Hz, 1H, H9), 1.96–1.84 (m, 4H, H10 and H10′), 1.53–1.44 and
1.11–1.02 (m, 4H, H11 and H11′), 1.39–1.20 (m, 9H, H12, H13, H14,
H15 and H16), 0.90 (t, J = 7.0 Hz, 3H, ―CH3). 13C NMR (100 MHz,
CDCl3): δ 154.4 (dm, J = 244.9 Hz, C3′), 149.8 (dm, J = 249.0 Hz, C1),
149.1 (dm, J = 248.3 Hz, C3), 148.7 (C8), 137.7 (dm, J = 246.6 Hz,
C2), 130.0 (C5), 127.0 (C7 and C7′), 124.8 (C6 and C6′), 116.3–115.9
1.25–1.19 (m, 2H, ―CH2CH2CH3), 0.91 (t, J = 7.2 Hz, 3H, ―CH3). 13
C
NMR (100 MHz, CDCl3): δ 154.4 (dm, J = 245.0 Hz, C3′), 149.7 (dm,
J = 249.3 Hz, C1), 149.1 (dm, J = 248.8 Hz, C3), 148.7 (C8), 137.7
(dm, J = 246.9 Hz, C2), 130.0 (C5), 127.0 (C7 and C7′), 124.8 (C6
and C6′), 116.3–115.9 (m, C4 ), 101.1–100.6 (m, C2′), 44.5 (C9), 39.7
Table 1. Optimization of reaction conditionsa
Entry
[Pd] source
Ligand
Solvent
Base
Yieldb (%)
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
—
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Trace
2
3c
PPh3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
95 (3a/3a′ = 5/3)
27
91
4
5
Trace
Trace
Trace
68
6
7
DMSO
8
1,4-Dioxane
Toluene
Toluene
Toluene
9
Trace
42
10
11
K3PO4
Na2CO3
Trace
aReaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), [Pd] source 10 mol%, ligand 20 mol%.
bIsolated yields.
c5 mol% Pd(OAc)2 and 10 mol% PCy3 were used.
Figure 1. Partial GC mass spectrum of the reaction mixture catalyzed by Pd(OAc)2/PPh3.
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Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 180–185

Palladium-catalyzed direct arylation of polyfluoroarene
(m, C4), 101.1–100.6 (m, C2′), 44.5 (C9), 44.1 (C13), 37.4 (C15), 34.3
(C10 and C10′), 33.5 (C11 and C11′), 32.2 (C12), 26.7 (C14), 22.7
(C16), 14.1 (C17). 19F NMR (376 MHz, CDCl3): δ À118.21 (t, J = 10.1
Hz, 1F, F2), À134.01 (ddd, J= 21.4, 9.9, 5.0 Hz, 1F, F3), À135.57 (d,
J= 21.1 Hz, 1F, F1), À165.00 (tdd, J= 21.6, 10.9, 6.1 Hz, 1F, F4). HRMS
calcd for C23H26F4 (M+) 378.1968; found: 378.1965. Anal. Calcd for
C23H26F4: C, 72.99; H, 6.92. Found: C, 72.75; H: 7.15.
(ddd, J = 21.5, 9.9, 5.0 Hz, 1F, F3), À135.58 (d, J = 21.6 Hz, 1F, F1),
À165.00 (tdd, J = 21.6, 10.9, 6.1 Hz, 1F, F4). HRMS calcd for
C29H36F4 (M+) 460.2754; found: 460.2748. Anal. Calcd for C29H36F4:
C, 75.62; H, 7.88. Found: C, 75.45; H: 8.11.
2,3,5,6-Tetrafluoro-4-methoxy-4′-(4-propylcyclohexyl)-1,1′-biphenyl (4j)
Yield 94%, white solid, m.p. 109–111°C. 1H NMR (400 MHz, CDCl3):
δ 7.37–7.26 (m, 4H, Ar―H), 4.11 (t, J = 1.3 Hz, 3H, ―OCH3),
2.52 (tt, J = 12.3, 3.3 Hz, 1H, H9 ), 1.96–1.87 (m, 4H, H10 and H10′),
1.53–1.43 and 1.11–1.02 (m, 4H, H11 and H11′), 1.39–1.27 (m, 3H,
H12 and H13), 1.25–1.19 (m, 2H, ―CH2CH2CH3), 0.91 (t, J = 7.2 Hz,
3H, ―CH3). 13C NMR (100 MHz, CDCl3): δ 148.7 (C8), 144.3 (dm,
J = 244.3 Hz, C3 and C3′), 141.2 (dm, J = 245.4 Hz, C2 and C2′),
137.3–137.0 (m, C1), 130.0 (C5), 127.1 (C7 and C7′), 124.6 (C6 and
C6′), 114.3 (t, J = 17.0 Hz, C4), 62.2 (t, J = 3.6 Hz, C16), 44.5 (C9),
39.7 (C13), 37.0 (C10 and C10′), 34.2 (C11 and C11′), 33.5 (C12),
20.0 (C14), 14.4 (C15). 19F NMR (376 MHz, CDCl3): δ À144.5 (dd,
J = 21.8, 8.6 Hz, 2F, F1), À157.7 (dd, J = 22.2, 8.7 Hz, 2F, F2). HRMS
calcd for C22H24OF4 (M+) 380.1756; found: 380.1758. Anal. Calcd
for C22H24F4O: C, 69.46; H, 6.36. Found: C, 69.17; H: 6.57.
2,3,4,6-Tetrafluoro-4′-(4′-pentyl-[1,1′-bi(cyclohexan)]-4-yl)-1,1′-biphenyl (4i)
Yield 62%, white solid, m.p. 148–150°C. 1H NMR (400 MHz, CDCl3):
δ 7.37–7.28 (m, 4H, Ar―H), 6.90–6.80 (m, 1H, ArF―H), 2.50 (tt, J= 11.6,
3.1 Hz, 1H, H9), 1.98–1.93 (m, 2H, H10 and H10′), 1.89–1.84 (m, 2H,
H11 and H11′), 1.79–1.73 (m, 4H, H10 and H10′, H14 and H14′ ),
1.55–1.42 (m, 2H, H12 and H13), 1.35–1.20 (m, 6H, H15 and
H15′, H18, H19), 1.21–1.13 (m, 6H, H11 and H11′, H14 and
H14′, H15 and H15′), 1.12–0.97 (m, 3H, H16 and H17), 0.93–0.85
(m, 5H, H20 and H21).13C NMR (100 MHz, CDCl3): δ 154.4 (dm,
J = 246.7 Hz, C3′), 149.6 (dm, J = 244.4 Hz, C1), 149.0 (dm, J = 243.1
Hz, C3), 148.7 (C8), 137.7 (dm, J = 245.8 Hz, C2), 130.0 (C5), 127.0
(C7 and C7′), 124.8 (C6 and C6′), 116.3–115.9 (m, C4), 101.1–100.6
(m, C2′), 44.5 (C9), 43.5 (C12), 42.9 (C13), 38.0 (C17), 37.5 (C19),
34.5 (C10 and C10′), 33.7 (C14 and C14′), 32.3 (C16), 30.3 (C18),
2,3,5,6-Tetrafluoro-4-methoxy-4′-(4-pentylcyclohexyl)-1,1′-biphenyl (4k)
30.1 (C15 and C15′), 26.7 (C11 and C11′), 22.7 (C20), 14.1 (C21). 19
F
Yield 88%, white solid, m.p. 107–109°C. 1H NMR (400 MHz, CDCl3):
δ 7.37–7.26 (m, 4H, Ar―H), 4.11 (t, J = 1.3 Hz, 3H, ―OCH3), 2.52
NMR (376 MHz, CDCl3): δ À118.21 (t, J = 10.1 Hz, 1F, F2), À134.01
Table 2. Pd(OAc)2-catalyzed arylation of polyfluoroarenes with aryl halidesa
Entry
1
2/R, X
4-OMe, Br (2b)
Product
T (°C)
t (h)
Yieldb (%)
1
Pentafluorobenzene (1a)
3b
3c
3d
3e
3f
80
80
3
3
90
70
Trace
90
85
86
96
72
85
98
55
77
63
61
73
84
60
86
52
81
2
1a
H, Br (2c)
3
1a
2-Me, Br (2d)
4-F, Br (2e)
80
3
4
1a
80
10
12
12
24
10
10
8
5
1a
4-NO2, Br (2f)
4-COMe, Br (2g)
4-COOMe, Br (2h)
4-ethenyl, Br (2i)
4-Ph-C6H4, Br (2j)
2-Bromonaphthalene (2k)
3-Bromopyridine (2l)
2a
80
6
1a
3g
3h
3i
80
7
1a
80
8
1a
80
9
1a
3j
80
10
11
12
13c
14c
15
16
17
18
19
20
1a
3k
3l
80
1a
80
24
8
1,2,4,5-Tetrafluoro-3-methoxybenzene (1c)
3m
3n
3o
3a
3b
3c
3h
3p
3m
80
1,2,4,5-Tetrafluorobenzene (1b)
2b
80
4
1,2,3,5-Tetrafluorobenzene (1d)
2b
80
12
4
1a
1a
1a
1a
1b
1c
4-Me, Cl (2m)
4-OMe, Cl (2n)
H, Cl (2o)
110
110
110
110
110
110
4
8
4-COMe, Cl (2p)
4-NO2, Cl (2q)
2m
12
24
5
aReaction conditions: 1.0 mmol polyfluoroarenes, 0.5 mmol arylhalides.
bIsolated yields.
cUsing 4.0 equiv. of polyfluoroarene.
Appl. Organometal. Chem. 2014, 28, 180–185
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X. Ma et al.
(tt, J = 12.3, 3.2 Hz, 1H, H9), 1.96–1.87 (m, 4H, H10 and H10′), 1.53–
1.43 and 1.12–1.02 (m, 4H, H11 and H11′), 1.35–1.21 (m, 9H, H12,
H13, H14, H15 and H16), 0.90 (t, J = 7.0 Hz, 3H, ―CH3). 13C NMR
(100 MHz, CDCl3): δ 148.7 (C8), 144.3 (dm, J = 244.3 Hz, C3 and
C3′), 141.2 (dm, J = 245.4 Hz, C2 and C2′), 137.3–137.0 (m, C1),
130.0 (C5), 127.1 (C7 and C7′), 124.6 (C6 and C6′), 114.3 (t, J = 17.0
Hz, C4), 62.2 (t, J = 3.6 Hz, C18), 44.5 (C9), 37.4 (C13), 37.3 (C15),
34.2 (C10 and C10′), 33.6 (C11 and C11′), 32.2 (C12), 26.7 (C14),
22.7 (C16), 14.1 (C17). 19F NMR (376 MHz, CDCl3): δ À144.5 (dd,
J = 22.2, 8.6 Hz, 2F, F1), À157.7 (dd, J = 22.2, 8.6 Hz, 2F, F2). HRMS
calcd for C24H28OF4 (M+) 408.2075; found: 408.2071. Anal. Calcd
for C24H28F4O: C, 70.57; H, 6.91. Found: C, 70.42; H: 7.12.
À157.5 (dd, J = 22.2, 8.6 Hz, 2F, F2). HRMS calcd for C30H38OF4 (M
+) 490.2855; found: 490.2853. Anal. Calcd for C30H38F4O: C, 73.44;
H, 7.81. Found: C, 73.30; H: 7.97.
Results and Discussion
Initially, the coupling reaction of pentafluorobenzene (1a), and
4-bromotoluene (2a) was selected as a model reaction to identify
an effective catalytic system and optimize the reaction conditions
(Table 1). Only Pd(OAc)2 showed no catalytic activity toward the
coupling reaction of 1a and 2a in the presence of Cs2CO3 as base
in toluene at 80°C (Table 1, entry 1). When Pd(OAc)2 and PPh3
ligand were used, a moderate yield of coupling product 3a with
an undesirable 40% yield of byproduct 3a′ was obtained and
confirmed by GC-MS analysis of the crude reaction mixture (Table 1,
entry 2). The byproduct might be tentatively ascribed to P―C bond
degradation of the ligand PPh3 at high temperature (Fig. 1).[12]
However, we were delighted to find that Pd(OAc)2/PCy3 as a highly
active catalyst for this reaction selectively afforded a 91% yield of
the only product 3a (Table 1, entry 4). Compared with Pd(OAc)2,
Pd(CH3CN)2Cl2 as palladium resource was inefficient in the arylated
reaction (Table 1, entry 5). A significantly low yield was obtained
with 5 mol% Pd(OAc)2 (Table 1, entry 3). In addition, we screened
several reaction conditions such as bases and solvents (Table 1,
entries 6–11). Also, the Pd(OAc)2/PCy3/Cs2CO3 system in toluene
at 80°C proved to be optimal for this reaction.
2,3,5,6-Tetrafluoro-4-methoxy-4′-(4′-pentyl-[1,1′-bi(cyclohexan)]-4-yl)-1,1′-
biphenyl (4l)
Yield 93%, white solid, m.p. 170–172°C. 1H NMR (400 MHz, CDCl3):
δ 7.36–7.29 (m, 4H, Ar―H), 4.11 (t, J = 1.2 Hz, 3H, ―OCH3),
2.50 (tt, J = 11.9, 3.4 Hz, 1H, H9), 1.98–1.94 (m, 2H, H10 and H10′),
1.90–1.84 (m, 2H, H11 and H11′), 1.78–1.74 (m, 4H, H10 and H10′,
H14 and H14′), 1.52–1.43 (m, 2H, H12 and H13), 1.32–1.20 (m, 6H,
H15 and H15′, H18, H19), 1.21–1.13 (m, 6H, H11 and H11′, H14
and H14′, H15 and H15′), 1.12–0.97 (m, 3H, H16 and H17), 0.90–
0.86 (m, 5H, H20 and H21).13C NMR (100 MHz, CDCl3): δ 148.7
(C8), 144.3 (dm, J = 244.3 Hz, C3 and C3′), 141.2 (dm, J = 245.2 Hz,
C2 and C2′), 137.2–137.0 (m, C1), 130.0 (C5), 127.1 (C7 and C7′),
124.5 (C6 and C6′), 114.3 (t, J = 17.2 Hz, C4), 62.2 (t, J = 3.6 Hz,
C22), 44.5 (C9), 43.4 (C12), 42.9 (C13), 37.9 (C17), 37.5 (C19), 34.5
(C10 and C10′), 33.7 (C14 and C14′), 32.3 (C16), 30.3 (C18), 30.1
(C15 and C15′), 26.7 (C11 and C11′), 22.7 (C20), 14.1 (C21). 19F
NMR (376 MHz, CDCl3): δ À144.4 (dd, J = 22.2, 9.0 Hz, 2F, F1),
Under the optimal reaction conditions, we investigated the
scope of Pd-catalyzed arylation of perfluorobenzene with various
aryl bromides. As summarized in Table 2, all arylation reactions
were very clean, and the corresponding polyfluoroarenes were
Table 3. Synthesis of fluorinated biphenyl compounds by Pd-catalyzed direct arylation of polyfluoroarenesa
Entry
Fluoroarene
R
Product
Yieldb (%)
1
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
4-(4-Propylcyclohexyl) (2r)
4a
4b
4c
4d
4e
4f
88
92
96
80
78
82
94
88
93
71
75
62
2
4-(4-Pentylcyclohexyl) (2s)
3
4-[4′-Pentyl-1,1′-bi(cyclohexyl)] (2t)
4-(4-Propylcyclohexyl) (2r)
4
5
4-(4-Pentylcyclohexyl) (2s)
6
4-[4′-Pentyl-1,1′-bi(cyclohexyl)] (2t)
4-(4-Propylcyclohexyl) (2r)
7
4j
8
4-(4-Pentylcyclohexyl) (2s)
4k
4l
9
4-[4′-Pentyl-1,1′-bi(cyclohexyl)] (2t)
4-(4-Propylcyclohexyl) (2r)
10
11
12
4g
4h
4i
4-(4-Pentylcyclohexyl) (2s)
4-[4′-Pentyl-1,1′-bi(cyclohexyl)] (2t)
aReaction conditions: 1.0 mmol polyfluoroarenes, 0.5 mmol arylbromides.
bIsolated yields.
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Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 180–185

Palladium-catalyzed direct arylation of polyfluoroarene
obtained in moderate to good yield. The electronic effects of the
substituents on the aromatic ring did not significantly affect the
reaction (Table 2, entries 1, 2 and 4–8). We found that the
catalyst system tolerated several reactive functional groups, such
as ―COCH3, ―COOMe, and ―CH = CH2. However, we failed to
perform the arylation with 1-bromo-2-methylbenzene and
pentafluorobenzene (Table 2, entry 3) for steric hindrance in the
substrate. When pentafluorobenzene reacted with 4-bromobiphenyl,
2-bromonaphthalene and 3-bromopyridine, respectively, the
corresponding arylated products were obtained in moderate to
excellent yield (Table 2, entries 9–11). Tetrafluorobenzenes such as
1,2,4,5-tetrafluoro-3-methoxybenzene could also be arylated with
4-bromotoluene in satisfactory yield (Table 2, entry 12), and 1,2,4,5-
tetrafluorobenzene and 1,2,3,5-tetrafluorobenzene also reacted
selectively with 1-bromo-4-methoxybenzene to give the arylated
products in 63% and 61% yield, respectively (Table 2, entries 13
and 14). Encouraged by this result, we investigated the arylation
of perfluorobenzene and aryl chlorides. Initially, the attempt to
obtain a satisfactory yield by reaction of pentafluorobenzene
with chlorobenzene in toluene at 80°C failed, but we found that
the reaction could be carried out smoothly at 110°C and provide
60% yield (Table 2, entry 17). The results showed that high
reaction temperature was beneficial in improving the arylation
of perfluorobenzene and aryl chlorides. The coupling reactions
between aryl chlorides with an electron-withdrawing group, such
as 4-COCH3, and 4-NO2 and pentafluorobenzene produced
biaryls with good yields (76% and 86%, respectively, Table 2,
entries 18 and 19). The electron-rich aryl chlorides reaction with
perfluorobenzene, such as 1-chloro-4-methylbenzene, and 1-
chloro-4-methoxybenzene also gave good yields (73%, 84%
and 81%, respectively, Table 2, entries 15, 16 and 20) under
the same conditions.
In addition, the liquid crystalline materials containing fluoro-
substituted phenyls are the most prominent for application in
thin-film transistor liquid crystal displays (TFT-LCDS). The long
and lath-like molecular structure of most fluorinated liquid crys-
talline compounds required in TFT-LCDS makes the formation
of CAryl―CAryl bonds very important in the synthesis reaction. In
general, most fluorinated liquid crystalline compounds can be
prepared through the Suzuki–Miyaura coupling reaction of
arylboronic acid with aryl halide.[13] Our interest was focused on
the concise preparation of polyfluorobiphenyl compounds with
Pd-catalyzed direct arylation of polyfluoroarenes with aryl bro-
mides. As expected, liquid crystal products 4a–4l could be
obtained through the treatment of aryl bromides with various
polyfluoroarenes in the presence of Pd(OAc)2/PCy3 and Cs2CO3
in toluene at 80°C for 10 h and the yields of polyfluorobiphenyl
compounds were 62–96% (Table 3). This procedure is a simple
and efficient method for the preparation of polyfluorobiphenyl
liquid crystal compounds at the laboratory scale.
method particularly attractive for the efficient preparation of fluo-
rinated liquid crystal compounds.
Acknowledgments
We gratefully acknowledge financial support of this work by the
National Basic Research Program of China (973 Program:
2012CB722603), the Ministry of Education Innovation Team (No.
IRT1161), the NSFC (No. 21103114), the Doctor Foundation of
Xinjiang Bingtuan (No. 2012BB010), and Start-Up Foundation for
Young Scientists of Shihezi University (No. RCZX201014, RCZX201015).
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Conclusions
In summary, we have described a simple and effective Pd(OAc)2/
PCy3 catalyst system for the direct arylation of polyfluoroarenes
with aryl bromides or even aryl chlorides in moderate to excellent
yield under mild conditions. The simplicity of the reaction proce-
dure coupled with the broad range of substrates renders this
Supporting Information
Additional supporting information may be found in the online
version of this article at the publisher’s web site.
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