Synthesis of polyfluorinated aryl ethers via ligand-free palladium-catalyzed CF activation of pentafluorobenzene

Article abstract of DOI:10.1016/j.jfluchem.2013.02.025

An efficient, ligand-free palladium-catalyzed method for the cross coupling reaction of pentafluorobenzene with phenols was developed. This reaction proceeds via a highly selective CF bond activation in the 3-position and is compatible with a variety of functional groups, delivering polyfluorinated aryl ethers in moderate to excellent yields.

Full text of DOI:10.1016/j.jfluchem.2013.02.025

Journal of Fluorine Chemistry 150 (2013) 117–123
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of polyfluorinated aryl ethers via ligand-free palladium-
catalyzed C–F activation of pentafluorobenzene
Lanbao Sun, Mingguang Rong, Dedao Kong, Zhengshuai Bai, Yaofeng Yuan, Zhiqiang
*
Weng
College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, China
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient, ligand-free palladium-catalyzed method for the cross coupling reaction of pentafluor-
obenzene with phenols was developed. This reaction proceeds via a highly selective C–F bond activation
in the 3-position and is compatible with a variety of functional groups, delivering polyfluorinated aryl
ethers in moderate to excellent yields.
Received 17 November 2012
Received in revised form 26 February 2013
Accepted 27 February 2013
Available online 7 March 2013
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
C–F activation
Palladium-catalyzed
Polyfluorinated aryl ethers
1. Introduction
C–F activation of a perfluoroaromatic.[27,28] Sandford and co-
workers reported the first example of palladium-catalyzed Suzuki-
The prevalence of polyfluoroarenes in materials and life science
has stimulated considerable interest to develop efficient methods
for the synthesis of polyfluoroarylated compounds [1–4]. The
traditional functionlization of polyfluoroarenes via deprotonation
of acidic hydrogens requires the use of a stoichiometric amount of
organometallic bases followed by the reactions with electrophiles
typically in harsh reaction conditions [5]. The transition-metal-
catalyzed direct functionalization of C–H bonds of polyfluoroar-
enes has been widely recognized, and much effort has been made
recently toward exploiting this strategy [6–19]. On the other hand,
the selective activation and functionalization of C–F bonds would
offer an attractive alternative synthetic route for the synthesis
of polyfluoroarene derivatives.
Various successful approaches for cross-coupling reactions of
polyfluoroarenes via C–F activation mediated by metal species
have been reported recently [20–24]. For example, Braun and co-
workers reported the first example of nickel-catalyzed C–F bond
activation of perfluorinated heterocyclic compounds in the Stille
vinylation of 2,3,5,6-tetrafluoropyridine and the Suzuki-Miyaura
arylation of 5-chloro-2,4,6-trifluoropyrimidine.[25,26] Radius
and co-workers employed an N-heterocyclic carbene stabilized
nickel(0) complex as the catalyst for the Suzuki-Miyaura
arylation of perfluorotoluene and perfluorobiphenyl via catalytic
Miyaura cross-coupling reaction for perfluorinated aromatic
system [29]. Love and co-workers found that Ni(COD)2/PPh3
catalyzes the cross-coupling of polyfluoroarenes to generate
functionalized fluorinated building blocks under mild conditions
[30–34]. Notably, Lu and others have developed an efficient
palladium-catalyzed C–F activation and C–C bond formation of
polyfluoroaryl oxazolines [35]. More recently, Nakamura and co-
workers have reported using hydroxyphosphine or alkoxydipho-
sphine ligand, nickel-catalyzed cross-coupling of polyfluoroarene
and Grignard reagents or organozinc reagents which can
selectively produce partially fluorinated arenes [36,37]. However,
many of these reactions suffered from limited substrate scope and
the requirement of using aryl fluorides with a directing group.
Moreover, most of these transformations are limited to the
construction of Caryl–Caryl bonds.
Given the importance of polyfluorinated diaryl ethers in
pharmaceutically active compounds [38] and as effective liquid
crystal dopants [39], the development of a practical catalyst
system that can be used to synthesize these molecules with broad
functional group compatibility and tolerance is desired.
To date, polyfluorinated diaryl ethers or alkyl aryl ethers have
been synthesized via nucleophilic aromatic substitution processes
[39–43,44]. However, early works showed that this method
resulted mostly in low to medium yield of products and usually
required longer reaction time, and the substrate scope was limited.
Our research focuses on the synthesis of fluorine-containing
compounds. Previously, we have developed an efficient way of
* Corresponding author. Fax: +86 59122866121.
E-mail address: zweng@fzu.edu.cn (Z. Weng).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.02.025

118
L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
trifluoromethylation of aryl iodides and terminal acetylenes by a
copper catalyst [45,46]. In this study, we report a ligand-free
palladium-catalyzed C–F activation method to synthesize poly-
fluorinated aryl ethers with high yield and broad functional group
compatibility by the cross coupling reaction between pentafluor-
obenzene with phenols.
We further tested the significant dependence of this coupling
on the nature of bases and solvents. When using Na2CO3 or K3PO4
as
a base, the corresponding product 3a was obtained in
comparable yields (entries 11 and 14), but the use of KOH or t-
BuONa as a base gave inferior results under the same conditions
(entries 12 and 13). Moreover, the use of other solvents such as
DMSO and NMP was proved to be inefficient (entries 15 and 16),
and DME, 1,4-dioxane, THF, diglyme, CH3CN and toluene led to
little or no product formation when used in place of DMF for these
transformations (entries 17–22).
2. Results and discussion
Our study commenced by examining the coupling reaction of
phenol with pentafluorobenzene using Pd(OAc)2 as the catalyst,
AgNO3 as the additive and K2CO3 as the base. The desired
polyfluorinated diaryl ether product 3a was obtained in 91%
isolated yield when the reaction was carried out in DMF at 120 8C
(Table 1, entry 3). Compound 3a was characterized by mass
spectroscopy, 1H, 13C and 19F NMR spectroscopy. Pd black was also
observed in the reaction mixture.
Pentafluorobenzene (C6HF5) as a substrate provides competi-
tion between C–F and C–H oxidative addition in the coupling
reactions. It should be noted that under a similar reaction
condition to those palladium catalyzed C–H bond activation of
pentafluorobenzene, our present catalytic reaction shows high
chemo- and regioselectivity for the C–F bond activation para to the
hydrogen substituent for the formation of the C–O bond.
Both of the palladium catalyst and AgNO3 additive appeared to
be essential to the reaction efficiency as the absence of either of
them dramatically reduced the product yields (entries 1 and 2)
under otherwise similar experimental conditions. The effects of
other additives were then examined on the coupling reactions. The
use of AgOAc, Ag2O, O2, and CuSO4 also provided satisfactory yields
(entries 4, 5, 7 and 8), while AgF and Cu(OAc)2 afforded the
coupling products in moderate yields (entries 6 and 9), but the
hypervalent iodine reagent, PhI(OAc)2, was not effective for this
reaction (entry 10).
Having discovered conditions for the palladium-catalyzed
coupling of pentafluorobenzene with phenols, the scope of various
phenols was examined (Table 2). The reactions with substrates
bearing methyl, dimethyl, tert-butyl and phenyl groups underwent
smooth reactions to give the corresponding products in excellent
isolated yields of 82 to 93% (entries 1–8). 1-Naphthol also provided
the desired ether products in a good yield of 92% (entry 9). Phenols
possess electron-donating groups, e.g. alkoxy and amino substi-
tuted at the meta- position, also gave good to excellent yields of
94%, 84% and 75% (entries 10–12). Reactions of phenol with amides
group occurred in modest yields of 63% (entry 13). The reactions
with substrates having electron-withdrawing groups such as an
acyl or a nitro group were well tolerated, giving rise to the coupling
products in 64% and 85% yields (entries 14 and 15). These groups
should allow further functional group manipulations for the
preparation of various derivatives. Noteworthily, the fluoro- and
chloro-containing phenols were effective for this transformation
and generated the corresponding products in promising yields
(entries 16 and 17). Heterocycles were also examined for the
coupling reaction. Interestingly, 8-Quinolinol was compatible with
the reaction to afford the ether product in 78% yield (entry 18). It
should be mentioned that most of the isolated polyfluorinated aryl
ether products (i.e. 3b–3s) are new compounds with broad
functionalities. Moreover, our results complemented the work of
Table 1
Optimization of palladium-catalyzed cross-coupling of pentafluorobenzene with phenols.a
Entry
Catalyst
Additive
Base
Solvent
T (8C)
Yield (%)b
1
2
None
AgNO3
none
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
KOH
DMF
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
90
28
44
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMF
3
AgNO3
AgOAc
Ag2O
DMF
93 (91)c
72
4
DMF
5
DMF
78
6
AgF
DMF
65
7
O2
DMF
76
8
CuSO4
Cu(OAc)2
PhI(OAc)2
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
DMF
80
9
DMF
66
10
11
12
13
14
15
16
17
18
19
20
21
22
DMF
36
DMF
90
DMF
68
t-BuONa
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
76
DMF
88
DMSO
NMP
DME
75
80
<5
<5
<5
20
Dioxane
THF
120
80
Diglyme
CH3CN
Toluene
120
90
<5
<5
120
a
Reaction conditions: 1a (0.20 mmol), 2 (0.10 mmol), additive (0.10 mmol), solvent (1.0 mL), under N2 atmosphere.
b
c
Yields were determined by 19F NMR analysis of the crude reaction mixture with trifluoromethoxybenzene as an internal standard.
Isolated yield.

L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
119
Table 2
Palladium-catalyzed synthesis of polyfluorinated aryl ethers.a
Entry
1
Phenol
Product
Isolated yield
87
2
3
4
85
85
82
90
93
5
6
7
8
83
85
9
92
10
11
94
84

120
L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
Table 2 (Continued )
Entry
12
Phenol
Product
Isolated yield
75
13
14
63
64
15
85
16
17
57
80
18
78
a
Reaction conditions: phenol (1.0 mmol), pentafluorobenzene (0.50 mmol), Pd(OAc)2 (0.050 mmol), AgNO3 (0.50 mmol), K2CO3 (1.0 mmol), DMF (3.0 mL), 120 8C, 12 h,
under N2 atmosphere.
Scheme 1. Plausible mechanism.

L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
121
Sandford who found that only limited alkyl-substituted phenols
reacted with polyfluoroarenes to produce polyfluorinated biphenyl
ether derivatives [39]. While current reaction conditions were
122.6 (s), 114.3 (s), 100.6 (t, J = 22.9 Hz). 19F NMR (376 MHz, CDCl3)
-138.7–138.9 (m, 2F), -154.0–154.1 (m, 2F). GC-MS m/z 242 (M+).
HRMS(EI): calcd. for C12H6F4O 242.0355; found 242.0357. IR
(KBr) 1641, 1591, 1521, 1485, 1202, 1067, 947, 839, 811, 754,
687 cmꢁ1
1,2,4,5-tetrafluoro-3-(p-tolyloxy)benzene (3b): Obtained as a
colorless oil in 87% yield (111.4 mg). 1H NMR (400 MHz, CDCl3)
7.04 (d, J = 7.6 Hz, 2H), 6.94–6.82 (m, 1H), 6.79 (d, J = 7.6 Hz, 2H),
2.24 (s, 3H). 13C NMR (101 MHz, CDCl3)
155.2 (s), 147.8–147.5
d
effective for
a
variety of pentafluorobenzene, the reactions
n
of 1,2,4,5-tetrafluorobenzene with phenol did not give any
polyfluorinated aryl ethers products.
.
A plausible mechanism for this reaction is depicted in Scheme 1.
The initiated SN20 attack of palladium species (A) on the
pentafluorobenzene (at 3-position of C6HF5) leads to the formation
of intermediate B, which undergoes C–F bond cleavage and
fluoride abstraction by AgNO3, and phenolate coordination to
afford intermediate C. Subsequent reductive elimination from C
would produce the polyfluorinated aryl ether 3, as well as the
palladium(0) species A, and complete the catalytic cycle.
d
d
(m), 145.3–145.0 (m), 142.9–142.7 (m), 140.4–140.2 (m), 133.3 (s),
130.2 (s), 115.4 (s), 101.6 (t, J = 22.9 Hz), 20.56 (s). 19F NMR
(376 MHz, CDCl3)
GC-MS m/z 256 (M+). HRMS(EI): calcd. for C13H8F4O 256.0511;
found 256.0510. IR (KBr) 3084, 2926, 1641, 1591, 1521, 1485,
1203, 1172, 1067, 947, 755 cmꢁ1
1,2,4,5-tetrafluoro-3-(o-tolyloxy)benzene (3c): Obtained as a
colorless oil in 85% yield (108.9 mg). 1H NMR (400 MHz, CDCl3)
d -138.8–139.0 (m, 2F), -154.3–154.2 (m, 2F).
n
.
3. Conclusions
d
7.33 (d, J = 7.4 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.11 (t, J = 7.3 Hz,
1H), 7.05–6.93 (m, 1H), 6.72 (d, J = 8.0 Hz, 1H), 2.52 (s, 3H). 13C
NMR (101 MHz, CDCl3) d155.6 (s), 147.9–147.6 (m), 145.4–145.2
In summary, we have developed an efficient, ligand-free
palladium-catalyzed method for the cross coupling reaction of
pentafluorobenzene with phenols. Our catalysis system proceeds
with high chemo- and regioselectivity for the C–F bond activation
in the para-position with respect to the hydrogen substituent. A
wide variety of phenols can be employed in this coupling reaction
to afford the corresponding polyfluorinated aryl ethers in
moderate to good yields. Further developments on synthesis of
other fluorine-containing compounds via palladium catalysis are
being pursued in our laboratory.
(m), 142.9–142.7 (m), 140.4–140.2 (m), 135.1–134.7 (m), 131.5
(s), 127.3 (s), 127.0 (s), 123.7 (s), 113.56 (s), 101.48 (t,
J = 23.0 Hz), 15.87 (s). 19F NMR (376 MHz, CDCl3)
d -138.9–
139.1 (m, 2F), -154.3–154.2 (m, 2F). GC-MS m/z 256 (M+).
HRMS(EI): calcd. for C13H8F4O 256.0511; found 256.0510. IR
(KBr)
1067, 945, 750 cmꢁ1
3-(4-(tert-butyl)phenoxy)-1,2,4,5-tetrafluorobenzene
Obtained as a colorless oil in 85% yield (126.7 mg). 1H NMR
(400 MHz, CDCl3) 7.39 (d, J = 7.8 Hz, 2H), 7.05–6.95 (m, 1H),
6.93(d, J = 7.8 Hz, 2H), 1.36 (s, 9H). 13C NMR (101 MHz, CDCl3)
n 3084, 2931, 1642, 1588, 1519, 1483, 1224, 1176, 1118,
.
(3d):
4. Experimental
d
1H NMR, 19F NMR and 13C NMR spectra were recorded using
BrukerAVIII 400 or AVIII 500 spectrometer. 1H NMR and 13C
NMR chemical shifts were reported in parts per million (ppm)
downfield from tetramethylsilane and 19F NMR chemical shifts
were determined relative to CFCl3 as the external standard and
low field is positive. Coupling constants (J) are reported in
Hertz (Hz). The residual solvent peak was used as an internal
d
155.0 (s), 147.8–147.6 (m), 146.7 (s), 145.4–145.1 (m), 143.0–
142.8 (m), 140.5–140.3 (m), 134.8–134.3 (m), 126.6 (s), 115.0 (s),
101.7 (t, J = 22.9 Hz), 34.29 (s), 31.40 (s). 19F NMR (376 MHz, CDCl3)
d
-138.86–139.02 (m, 2F), -154.08 (dt, J = 17.8, 8.6 Hz, 2F). GC-MS
m/z 298 (M+). HRMS(EI): calcd. for C16H14F4O 298.0981; found
298.0985. IR (KBr) 3085, 2966, 1641, 1606, 1517, 1483, 1221,
1175, 1067, 944, 831, 716, 546 cmꢁ1
3-(2-(tert-butyl)phenoxy)-1,2,4,5-tetrafluorobenzene
Obtained as a colorless oil in 82% yield (122.2 mg). 1H NMR
(400 MHz, CDCl3) 7.47 (d, J = 7.5 Hz, 1H), 7.18–7.10 (m, 2H), 7.06–
6.93 (m, 1H), 6.65 (d, J = 7.9 Hz, 1H), 1.55 (s, 9H). 13C NMR
(101 MHz, CDCl3) 156.0 (s), 148.0–147.7 (m), 145.5–145.2 (m),
n
reference: 1H NMR (chloroform
d
7.26) and 13C NMR (chloro-
.
form 77.0). The following abbreviations were used to explain
d
(3e):
the multiplicities: s = singlet, d = doublet, t = triplet, q = quar-
tet, m = multiplet, br = broad. All reagents were received from
commercial sources. Solvents were freshly dried and degassed
according to the purification handbook Purification
of Laboratory Chemicals prior to use. Column chromatography
purifications were performed by flash chromatography using
Merck silica gel 60.
d
d
142.7–142.6 (m), 140.3–140.1 (m), 138.3 (s), 134.1–133.9 (m),
127.5 (s), 127.1 (s), 123.5 (s), 113.8 (s), 101.4 (t, J = 23.0 Hz), 34.95
(s), 29.85 (s). 19F NMR (376 MHz, CDCl3)
d
-138.78–138.94 (m, 2F),
-153.96 (dt, J = 21.3, 8.7 Hz, 2F). GC-MS m/z 298 (M+). HRMS(EI):
calcd. for C16H14F4O 298.0981; found 298.0987. IR (KBr)
3084, 2963, 2873, 1642, 1520, 1482, 1364, 1189, 945, 809, 749,
482 cmꢁ1
2-(2,3,5,6-tetrafluorophenoxy)-1,10-biphenyl (3f): Obtained as
a colorless oil in 90% yield (143.2 mg). 1H NMR (400 MHz, CDCl3)
7.73–7.70 (m, 2H), 7.55–7.51 (m, 3H), 7.47–7.43 (m, 1H), 7.38–7.27
(m, 2H), 7.00–6.89 (m, 2H). 13C NMR (101 MHz, CDCl3)
154.0 (s),
4.1. General procedure for Pd-catalyzed synthesis of
polyfluorinated aryl ethers
n
.
To a septum-capped 10 mL Schlenck tube were added Pd(OAc)2
(10 mol%), K2CO3 (2 equiv.), AgNO3 (1 equiv.), and phenols
(1.0 mmol, 2 equiv.) under N2, followed by pentafluorobenzene
(1.0 equiv.) and DMF (3.0 mL). The reaction mixture was heated at
120 8C (oil bath) for 12 h. After the reaction was cooled to room
temperature, ethyl ether (10 mL) and water (5 mL) were added.
The organic layer was separated, and the aqueous phase was
extracted with ethyl ether (10 mL ꢀ 2). The combined organic
layers were dried over anhydrous MgSO4, filtered and concentrat-
ed. The residue was purified by column chromatography (SiO2) to
give the pure product.
d
d
147.9–147.6 (m), 145.4–145.1 (m), 142.7–142.5 (m), 140.2–140.0
(m), 137.4 (s), 134.8–134.5 (m), 131.7 (s), 131.5 (s), 129.5 (s), 128.7
(s), 128.3 (s), 127.6 (s), 124.2 (s), 114.6 (s), 101.49 (t, J = 23.0 Hz).
19F NMR (376 MHz, CDCl3)
d
-138.87 (dt, J = 19.8, 9.7 Hz, 2F), -
154.05–154.30 (m, 2F). GC-MS m/z 318 (M+). HRMS(EI): calcd. for
18H10F4O 318.0668; found 318.0666. IR (KBr) 3078, 1642, 1520,
1483, 1258, 1195, 1119, 1064, 946, 722 cmꢁ1
C
n
.
1,2,4,5-tetrafluoro-3-phenoxybenzene (3a): Obtained as
colorless oil in 91% yield (110.2 mg). 1H NMR (400 MHz, CDCl3)
7.27–7.18 (m, 2H), 7.06–6.97 (m, 1H), 6.90–6.78 (m, 3H). 13C
NMR (101 MHz, CDCl3) 156.0 (s), 146.7–146.4 (m), 144.2–143.9
(m), 141.8–141.5 (m), 139.3–139.0 (m), 133.2–133.0 (m), 128.6 (s),
a
3-(3,5-dimethylphenoxy)-1,2,4,5-tetrafluorobenzene (3g):
Obtained as a yellow oil in 93% yield (125.6 mg). 1H NMR
d
(400 MHz, CDCl3)
6.72 (m, 2H), 2.41–2.40 (m, 6H). 13C NMR (101 MHz, CDCl3)
(s), 155.7 (s), 147.9–147.6 (m), 145.5–145.2 (m), 143.1–142.9 (m),
d
7.05–6.97 (m, 1H), 6.88–6.86 (m, 1H), 6.74–
d
d
157.3

122
L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
140.6–140.4 (m), 139.9 (s), 125.6 (s), 113.2 (s), 101.7 (t,
6.22 (s, 2H), 3.53 (s, 2H). 13C NMR (101 MHz, CDCl3)
d 152.7 (s),
150.2, 147.8–147.5 (m), 145.3–145.1 (m), 142.6–142.4 (m), 140.1–
140.0 (m), 139.4 (s), 136.0 (s), 129.8 (s), 126.1 (s), 123.3 (s), 122.2
(s), 112.2 (s), 101.83 (t, J = 22.9 Hz). 19F NMR (376 MHz, CDCl3)
d -
J = 23.0 Hz), 21.18 (s). 19F NMR (376 MHz, CDCl3)
d
-138.86–
139.25 (m, 2F), -154.14–154.43 (m, 2F). GC-MS m/z 270 (M+).
HRMS(EI): calcd. for C14H10F4O 270.0668; found 270.0667. IR (KBr)
n
3082, 2924, 1642, 1619, 1592, 1486, 1290, 1143, 1079, 946, 834,
138.83–139.06 (m, 2F), -154.15 (dt, J = 21.8, 8.6 Hz, 2F). GC-MS m/z
257 (M+). HRMS(EI): calcd. for C12H7F4NO 257.0464; found
716, 682 cmꢁ1
.
3-(2,3-dimethylphenoxy)-1,2,4,5-tetrafluorobenzene (3h):
Obtained as a white solid in 83% yield (112.1 mg); mp 93–95 8C.
257.0462. IR (KBr)
n 3325, 1642, 1535, 1487, 1132, 1259, 1147,
1063, 949, 855, 775 cmꢁ1
.
1H NMR (400 MHz, CDCl3)
d
7.04–6.92 (m, 3H), 6.52 (d, J = 8.0 Hz,
N-(4-(2,3,5,6-tetrafluorophenoxy)phenyl)acetamide (3n):
1H), 2.37 (s, 6H). 13C NMR (101 MHz, CDCl3)
d
155.5 (s), 147.8–
Obtained as a light yellow solid in 63% yield (94.3 mg); mp
147.6 (m), 145.4–145.1 (m), 142.8–142.6 (m), 140.4–140.2 (m),
139.0 (s), 135.2 (s), 125.9 (s), 125.8 (s), 125.2 (d, J = 1.8 Hz), 111.2
(s), 101.3 (t, J = 23.0 Hz), 20.0 (s), 11.8 (s). 19F NMR (376 MHz,
132 ꢁ 134 8C. 1H NMR (400 MHz, CDCl3)
d 8.05 (s, 1H), 7.40–7.33
(m, 2H), 6.90–6.83 (m, 1H), 6.80 (d, J = 9.0 Hz, 2H), 2.03 (s, 3H). 13
C
NMR (101 MHz, CDCl3)
d 168.9 (s), 153.6 (s), 147.8–147.5 (m),
CDCl3)
m/z 270 (M+). HRMS(EI): calcd. for C14H10F4O 270.0668; found
270.0664. IR (KBr) 3092, 2919, 2851, 1643, 1581, 1189, 1126,
941, 847, 765, 717 cmꢁ1
d
-138.99–139.21 (m, 2F), -154.77–154.98 (m, 2F). GC-MS
145.4–145.1 (m), 142.8–142.6 (m), 140.3–140.1 (m), 134.6–134.3
(m), 134.0 (s), 121.8 (s), 116.0 (s), 101.85 (t, J = 22.9 Hz), 24.15 (s).
n
19F NMR (376 MHz, CDCl3)
d
-138.61–138.84 (m, 2F), -154.27 (ddd,
J = 21.5, 9.7, 7.1 Hz, 2F). GC-MS m/z 299 (M+). HRMS(EI): calcd. for
14H9F4NO2 299.0569; found 299.0565. IR (KBr) 3288, 1660,
1507, 1487, 1207, 1177, 1070, 943, 831, 715 cmꢁ1
.
3-(2,5-dimethylphenoxy)-1,2,4,5-tetrafluorobenzene (3i):
Obtained as a white solid in 85% yield (114.8 mg); mp 52–55 8C.
C
n
.
1H NMR (400 MHz, CDCl3)
d
7.14 (d, J = 7.4 Hz, 1H), 7.03–6.91 (m,
1H), 6.86 (d, J = 7.4 Hz, 1H), 6.44 (s, 1H), 2.39 (s, 3H), 2.26 (s, 3H).
13C NMR (101 MHz, CDCl3)
155.4 (s), 147.8–147.5 (m), 145.4–
1-(4-(2,3,5,6-tetrafluorophenoxy)phenyl)ethanone (3o): Obtained
as a white solid in 64% yield (90.9 mg); mp 74–76 8C. 1H NMR
d
(400 MHz, CDCl3)
d
7.95–7.85 (m, 2H), 7.02–6.89 (m, 3H), 2.51 (s,
196.4 (s), 160.4 (s), 147.6–147.8
145.1 (m), 142.8–142.6 (m), 140.4–140.2 (m), 137.0 (s), 131.2 (s),
3H). 13C NMR (101 MHz, CDCl3)
d
124.2 (d, J = 31.8 Hz), 114.3 (s), 101.4 (t, J = 23.0 Hz), 21.04 (s),
(m), 145.4–145.1 (m), 142.7–142.5 (m), 140.2–140.0 (m), 133.1 (s),
15.53 (s). 19F NMR (376 MHz, CDCl3)
d
-138.92–139.15 (m, 2F), -
154.17–154.37 (m, 2F). GC-MS m/z 270 (M+). HRMS(EI): calcd. for
14H10F4O 270.0668; found 270.0667. IR (KBr) 3096, 2923, 2857,
1644, 1515, 1489, 1243, 1125, 941, 842, 813, 713 cmꢁ1
130.7 (s), 115.25 (s), 102.62 (t, J = 22.9 Hz), 26.44 (s). 19F NMR
(376 MHz, CDCl3)
10.0, 7.1 Hz, 2F). GC-MS m/z 284 (M+). HRMS(EI): calcd. for
14H8F4O2 284.0460; found 284.0458. IR (KBr) 3045, 1678,
1644, 1599, 1504, 1488, 1268, 1220, 1166, 938, 847, 716, 590 cmꢁ1
d -137.94–138.09 (m, 2F), -153.66 (ddd, J = 21.5,
C
n
.
C
n
1-(2,3,5,6-tetrafluorophenoxy)naphthalene (3j): Obtained as a
white solid in 92% yield (134.4 mg); mp 61–63 8C. 1H NMR
.
1,2,4,5-tetrafluoro-3-(3-nitrophenoxy)benzene (3p): Obtained
(400 MHz, CDCl3)
d
8.32 (dd, J = 6.3, 2.8 Hz, 1H), 7.80 (dd, J = 6.1,
as a light yellow solid in 85% yield (122.0 mg); mp 65 ꢁ 67 8C. 1
H
2.9 Hz, 1H), 7.51 (dt, J = 7.5, 7.0 Hz, 3H), 7.24 (t, J = 8.0 Hz, 1H), 6.93
(tt, J = 9.9, 7.0 Hz, 1H), 6.59 (d, J = 7.7 Hz, 1H). 13C NMR (101 MHz,
NMR (400 MHz, CDCl3) d 8.04 (d, J = 8.1 Hz, 1H), 7.81 (s, 1H), 7.57 (t,
J = 8.0 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.17–7.02 (m, 1H). 13C NMR
(101 MHz, CDCl3) 157.3 (s), 149.3 (s), 147.9–147.7 (m), 145.4–
CDCl3)
d
153.2 (s), 147.9–147.6 (m), 145.4–145.2 (m), 143.0–142.7
d
(m), 140.5–140.2 (m), 134.8 (s), 134.6–134.3 (m), 127.7 (s), 127.0
(s), 126.2 (s), 125.2 (s), 124.8 (s), 123.6 (s), 121.6 (s), 107.6 (s), 102.1
145.2 (m), 142.6–142.4 (m), 140.1–139.9 (m), 133.2–133.0 (m),
130.7 (s), 121.9 (s), 118.8 (s), 110.7 (s), 103.1 (t, J = 22.9 Hz). 19F
(t, J = 22.9 Hz). 19F NMR (376 MHz, CDCl3)
d
-138.69–138.86 (m,
2F), -153.98–154.17 (m, 2F). GC-MS m/z 292 (M+). HRMS(EI): calcd.
for C16H8F4O 292.0511; found 292.0507. IR (KBr) 3093, 1642,
1599, 1577, 1513, 1493, 1231, 1177, 1104, 938, 788, 766 cmꢁ1
1,2,4,5-tetrafluoro-3-(3-methoxyphenoxy)benzene (3k):
NMR (376 MHz, CDCl3)
J = 21.8, 8.6 Hz, 2F). GC-MS m/z 287 (M+). HRMS(EI): calcd. for
12H5F4NO3 287.0206; found 287.0205. IR (KBr) 1642, 1532,
1438, 1351, 1220, 1173, 958, 755, 715 cmꢁ1
1,2,4,5-tetrafluoro-3-(4-fluorophenoxy)benzene (3q): Obtained
as a yellow oil in 57% yield (74.1 mg). 1H NMR (400 MHz, CDCl3)
7.09–6.94 (m, 5H). 13C NMR (101 MHz, CDCl3)
160.2 (s), 157.8 (s),
d -130.78–142.50 (m, 2F), -154.15 (dt,
n
C
n
.
.
Obtained as
a
white solid in 94% yield (127.9 mg); mp
d
49 ꢁ 51 8C. 1H NMR (400 MHz, CDCl3)
d
7.26 (t, J = 8.3 Hz, 1H),
d
7.04–6.96 (m, 1H), 6.73–6.70 (m, 1H), 6.62 (t, J = 2.4 Hz, 1H), 6.59–
6.56 (m, 1H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3)
153.2 (s), 147.9–147.6 (m), 145.4–145.1 (m), 142.8–142.6 (m),
140.3–140.1 (m), 134.7–134.4 (m), 117.1 (d, J = 8.3 Hz), 116.4 (s),
116.2 (s), 101.9 (t, J = 22.9 Hz). 19F NMR (376 MHz, CDCl3)
d-119.53–
119.72 (m, 1F), -138.47–138.63 (m, 2F), -154.19–154.32 (m, 2F). GC-
MS m/z 260 (M+). HRMS(EI): calcd. for C12H5F5O 260.0261; found
d
161.0 (s),
158.2 (s), 147.8–147.5 (m), 145.3–145.0 (m), 142.9–142.7 (m),
140.4–140.2 (m), 134.3–134.0 (m), 130.2 (s), 109.1 (s), 107.5 (s),
102.3 (s), 102.0 (t, J = 23.2 Hz), 55.3 (s). 19F NMR (376 MHz, CDCl3)
d
-136.64–140.96 (m, 2F), -154.21 (ddd, J = 21.5, 9.8, 7.1 Hz, 2F).
260.0259. IR (KBr)
832, 736, 513 cmꢁ1
n 3088, 1642, 1502, 1485, 1274, 1190, 1068, 945,
.
GC-MS m/z 292 (M+). HRMS(EI): calcd. for C13H8F4O2 272.0460;
found 272.0452. IR (KBr)
1063, 949, 855, 771 cmꢁ1
n
.
3075, 2976, 1601, 1529, 1259, 1147,
3-(4-chlorophenoxy)-1,2,4,5-tetrafluorobenzene (3r): Obtained
as a colorless oil in 80% yield (110.6 mg). 1H NMR (400 MHz, CDCl3)
7.38–7.23 (m, 2H), 7.09–6.85 (m, 3H). 13C NMR (101 MHz, CDCl3)
d
d
3-(2-ethoxyphenoxy)-1,2,4,5-tetrafluorobenzene (3l): Obtained
as a white solid in 84% yield (120.2 mg); mp 62 ꢁ 64 8C. 1H NMR
155.7 (s), 147.8–147.6 (m), 145.4–145.1 (m), 142.8–142.6 (m),
140.3–140.1 (m), 134.2–133.9 (m), 129.8 (s), 129.0 (s), 116.9 (s),
102.2 (t, J = 22.9 Hz). 19F NMR (376 MHz, CDCl3)
d -138.38 (qt,
J = 11.7, 1.8 Hz,2F), -154.03(ddd,J = 21.5, 9.9, 7.0 Hz, 2F). GC-MSm/z
275 (M+). HRMS(EI): calcd. for C12H5ClF4O 275.9965; found
(400 MHz, CDCl3) d 6.97–6.91 (m, 1H), 6.87–6.78 (m, 2H), 6.78–6.67
(m, 2H), 3.91 (q, J = 7.0 Hz, 2H), 1.18 (t, J = 7.0 Hz, 3H). 13C NMR
(101 MHz, CDCl3) 149.1 (s), 147.6–147.4 (m), 146.3 (s), 145.2 –
d
144.9 (m), 142.4–142.2 (m), 140.0–139.8 (m), 136.3–136.0 (m),
124.9 (s), 120.8 (s), 117.9 (s), 114.1 (s), 100.4 (t, J = 23.0 Hz), 64.5 (s),
275.9961; IR (KBr)
n 3086, 1642, 1588, 1521, 1485, 1210, 1177,
14.5 (s). 19F NMR (376 MHz, CDCl3)
d
-139.97–140.09 (m, 2F), -
155.22–155.36 (m, 2F). GC-MS m/z 286 (M+). HRMS(EI): calcd. for
14H10F4O2 286.0617; found 286.0619. IR (KBr) 3094, 2982, 1641,
1605, 1587, 1320, 1253, 1122, 1196, 927, 835, 752 cmꢁ1
1066, 949, 827, 716, 502 cmꢁ1
.
8-(2,3,5,6-tetrafluorophenoxy)quinoline (3s): Obtained as a
light yellow solid in 78% yield (114.3 mg); mp 97–99 8C. 1H NMR
C
n
.
(400 MHz, CDCl3)
J = 8.1 Hz, 1H), 7.58–7.48 (m, 1H), 7.44 (t, J = 7.9 Hz, 1H), 7.09–6.92
(m, 2H). 13C NMR (101 MHz, CDCl3)
152.7 (s), 150.2 (s), 147.8–
147.6 (m), 145.4–145.1 (m), 142.7–142.4 (m), 140.2–140.0 (m),
d 9.02 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.62 (d,
3-(2,3,5,6-tetrafluorophenoxy)aniline (3m): Obtained as
yellow oil in 75% yield (96.4 mg). 1H NMR (400 MHz, CDCl3)
a
d
d
6.98 (t, J = 8.0 Hz, 1H), 6.92–6.79 (m, 1H), 6.33 (d, J = 7.9 Hz, 1H),

L. Sun et al. / Journal of Fluorine Chemistry 150 (2013) 117–123
123
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139.4 (s), 136.0 (s), 135.1–134.6 (m), 129.8 (s), 126.1 (s), 123.3 (s),
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Acknowledgments
We thank Prof. Kuo-Wei Huang for useful discussion and
acknowledge the financial support from National Natural Science
Foundation of China (21072030) and Fuzhou University (022318).
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Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in the
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