Pd-catalyzed direct arylation of polyfluoroarenes on water under mild conditions using PPh3 ligand

Article abstract of DOI:10.1021/jo300036d

We report a Pd-catalyzed direct arylation of polyfluoroarenes with aryl iodides. The advantages of this reaction are its high reaction efficiency, excellent functional group compatibility, mild reaction conditions (70 °C), inexpensive PPh₃ ligand, and use of pure water as reaction medium. The usefulness of this reaction has also been demonstrated by rapid preparation of highly functionalized polyfluoroarenes via iterative Pd-catalyzed C-H bond functionalization.

Full text of DOI:10.1021/jo300036d

Note
pubs.acs.org/joc
Pd-Catalyzed Direct Arylation of Polyfluoroarenes on Water under
Mild Conditions Using PPh3 Ligand
Fei Chen, Qiao-Qiao Min, and Xingang Zhang*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: We report a Pd-catalyzed direct arylation of polyfluoroarenes with aryl iodides. The advantages of this reaction are
its high reaction efficiency, excellent functional group compatibility, mild reaction conditions (70 °C), inexpensive PPh3 ligand,
and use of pure water as reaction medium. The usefulness of this reaction has also been demonstrated by rapid preparation of
highly functionalized polyfluoroarenes via iterative Pd-catalyzed C−H bond functionalization.
iaryls containing polyfluoroarene structural moieties are
interesting compounds in materials and life sciences.1 In
part of our ongoing research,7,2e herein we demonstrated our
results on the Pd-catalyzed direct arylation of polyfluoroarenes
with aryl iodides, which featured its high reaction efficiency,
excellent functional group compatibility, mild reaction con-
ditions (70 °C), inexpensive PPh3 ligand, and use of pure water
as reaction medium (Scheme 1).
B
particular, such fluorinated compounds play an important role
as active materials in electronic devices, such as organic light-
emitting diodes (OLEDs) and field-effect transistors (FETs).1d
Compared to the nonfluorinated counterparts, owing to its
strong electron-withdrawing effect, the polyfluorinated aryl
group can significantly enhance the photoluminescence
efficiency, minimize the self-quenching behavior, and lower
the HOMO and LUMO energy levels.1d Hence, it is of great
synthetic interest to develop an efficient reactions to access
these useful compounds. In the past few years, significant
progress has been made in the transition-metal-catalyzed direct
formation of C−C bonds between polyfluoroarenes and
arylhalides/arenes.2 As an alternative C−C bond-forming
strategy, this direct arylation of C−H bonds3 represents a
more efficient access to the polyfluoroaryl-aryls. These
reactions are straightforward and attractive; however, the
majority of these reactions occur at very high temperature
(often above 80 °C) or employ expensive electron-rich bulky
phosphine ligand,2 which restricts their widespread synthetic
applications, in particular in large-scale processes. Conse-
quently, to overcome these drawbacks, it is still highly desirable
to develop efficient mild reactions by using low cost and readily
available ligands.
Recently, from the economical and environmental point of
view, the use of water as solvent has attracted much interests
because of its innate advantages, such as low cost, ready
availability, nontoxicity, and nonflammability.4 Moreover, the
use of water as solvent can also potentially improve reactivities
and selectivities, simplify the workup procedures, and allow
mild conditions.4,5 Despite the advantages that water possess,
the transition-metal-catalyzed direct arylation of polyfluoroar-
enes by using pure water as reaction medium without the
addition of any organic cosolvents has not been reported.6 As a
Scheme 1. Pd-Catalyzed Direct Arylation of
Polyfluoroarenes with Aryl Iodides
We began this study by choosing pentafluorobenzene 1 and
1-iodo-4-methylbenzene 2a as model substrates (Table 1).
Initially, a Pd(OAc)2/PPh3 catalytic system, which was
successfully used in our previous work on the direct benzylation
and allylation of polyfluoroarenes,7b,d was investigated.
However, when the reaction was carried out with Pd(OAc)2
(10 mol %), PPh3 (20 mol %), and K2CO3 (2.0 equiv) in H2O
at 80 °C, no desired product 3a was afforded (Table 1, entry 1).
Given that silver salts are commonly employed to abstract
halide anions from transition-metal complexes, thus rendering
them more electrophilic and facilitating the catalytic cycle,8
Ag2CO3 (0.5 equiv) in conjunction with K2CO3 (2.0 equiv)
was examined, providing 3a in 89% yield (Table 1, entry 2). A
comparable yield was also obtained by sole use of Ag2CO3
(Table 1, entry 3), indicating the essential roles of the silver
salt, which may function as both a base and halide scavenger in
the palladium catalytic cycle. However, the exact mechanism of
Received: January 11, 2012
Published: February 16, 2012
© 2012 American Chemical Society
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a
Table 1. Optimization of Pd-Catalyzed Direct Arylation of Pentafluorobenzene 1 with 1-Iodo-4-methylbenzene 2a
b
entry
1 (equiv)
2a (equiv)
x
y
base (equiv)
K2CO3 (2.0)
temp (°C)
time (h)
yield (%)
1
3.0
3.0
3.0
3.0
3.0
2.0
1.5
1.5
1.5
1.5
1.5
1
1
1
1
1
1
1
1
1
1
1
10
10
10
5
20
20
20
10
10
10
10
10
10
80
80
80
80
70
70
70
70
50
70
70
10
10
10
10
10
10
16
24
24
24
24
NR
89
2
K2CO3 (2.0) Ag2CO3 (0.5)
Ag2CO3 (1.0)
3
90
4
Ag2CO3 (1.0)
80
5
5
Ag2CO3 (0.75)
Ag2CO3 (0.75)
Ag2CO3 (0.75)
Ag2CO3 (0.75)
Ag2CO3 (0.75)
Ag2CO3 (0.75)
78
6
5
82
7
5
86
8
5
90
9
5
74
10
11
5
NR
NR
10
Ag2CO3 (0.75)
a
b
Reaction conditions (unless otherwise specified): 1 (0.9 mmol), H2O (2.5 mL). Isolated yield.
a
Table 2. Pd-Catalyzed Direct Arylation of Pentafluorobenzene 1 with Aryl Iodides 2
a
Reaction conditions (unless otherwise specified): 1 (1.5 equiv), 2 (0.9 mmol), H2O (2.5 mL), 70 °C, 24 h. All reported yields are isolated yields.
Reaction run in DMF.
b
the silver salt in the catalytic cycle is unclear at this stage.
demonstrating the pivotal role of the Pd-catalyst in the catalytic
cycle (Table 1, entries 11 and 12).
Further optimizing the reaction conditions, we found that 90%
yield of 3a still could be provided by reducing the Pd(OAc)2
loading to 5 mol % with utilization of 1.5 equiv of 1 and 0.75
equiv of Ag2CO3 at 70 °C for 24 h (Table 1, entry 8). A
decreased yield (74%) was observed when the reaction
temperature was decreased to 50 °C (Table 1, entry 9). The
absence of PPh3 or Pd(OAc)2 did not furnish 3a,
A variety of pentafluorophenyl-aryls were generated by the
present method, and good to high yields were obtained (Table
2). Substrates bearing electron-rich or electron-withdrawing
groups furnished the corresponding products smoothly. Typical
functional groups, such as ester and nitro, are also tolerated by
the reaction conditions (3e−f). Importantly, the successful
formation of 3h with intact bromide provides a good
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Note
a
Table 3. Pd-Catalyzed Direct Arylation of Fluoroarene 4 with Aryl Iodides 2
a
Reaction conditions (unless otherwise specified): 4 (1.5 equiv), 2 (0.9 mmol), H2O (2.5 mL), 70 °C, 24 h. All reported yields are isolated yields.
Reaction run in DMF. Yield of diarylated product. 4 (4.0 equiv), 2 (0.6 mmol), H2O (2.5 mL), 70 °C, 24 h.
b
c
d
Scheme 2. Iterative Pd-Catalyzed C−H Bond Functionalization
opportunity for further formation of carbon−carbon or
carbon−heteroatom bonds by transition-metal-catalyzed cou-
pling and other reactions (3h). For example, compound 3h has
been directly introduced into DNA to study the hydrophobic,
aromatic pairs that are orthogonal to the natural base-pair in
their recognition properties.9 For 3-thiophenyl substituted 3i,
only a reasonable yield was afforded due to the formation of
byproduct and lack of consumption of starting material. To
address this issue, DMF was employed, providing 3i in 70%
yield (3i).
To further ascertain the scope of this methodology, a variety
of fluoroarenes 4 with aryl iodides were investigated (Table 3).
For substrates bearing 3 or 4 fluorine atoms contain more than
one reaction site, moderate to good yields of monoaryl
substituted products were still observed (Table 3, 3j−k, 3q).
Although 2,4-difluoro-1-nitrobenzene furnished 3r in low yield
under standard conditions, the utility of DMF could improve
the yield to 78% with a good regioselectivity (Table 3, 3r).
Again useful functional groups showed good tolerance to the
reaction conditions (Table 3, 3l, 3n, 3o, and 3r).
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Note
equiv) under N2, followed by fluoroarene (1.5 equiv). After stirring for
1 min, deionized water (2.5 mL) was added, and the reaction mixture
was warmed to 70 °C (oil bath) and stirred for 24 h. The reaction was
cooled to room temperature, and EtOAc (80 mL) and water (40 mL)
were added. The organic layer was separated, and the aqueous phase
was extracted with EtOAc (40 mL × 2). The combined organic layers
were dried over anhydrous Na2SO4, filtered, and concentrated. The
residue was purified by column chromatography to give desired
product.
General Procedure for Pd-Catalyzed Direct Arylation of
Polyfluoroarenes with Aryl Iodides in DMF. To a septum-capped
25 mL Schlenck tube were added Pd(OAc)2 (5 mol %), PPh3 (10 mol
%), Ag2CO3 (0.75 equiv), and aryl iodide (0.9 mmol, 1.0 equiv) under
N2, followed by fluoroarene (1.5 equiv) and DMF (2.5 mL). The
reaction mixture was warmed to 70 °C (oil bath) and stirred for 24 h.
The reaction was cooled to room temperature, and EtOAc (80 mL)
and water (40 mL) were added. The organic layer was separated, and
the aqueous phase was extracted with EtOAc (40 mL × 2). The
combined organic layers were dried over anhydrous Na2SO4, filtered,
and concentrated. The residue was purified by column chromatog-
raphy to give desired product.
The usefulness of this protocol can also be featured by rapid
preparation of highly functionalized polyfluoroarenes via
iterative Pd-catalyzed C−H bond functionalization. As shown
in Scheme 2, after selective Pd-catalyzed direct C−H bond
arylation of 1,2,4,5-tetrafluorobenzene, the resulting compound
3j was directly alkenylated by Pd-catalyzed oxidative
olefination7a to furnish a large conjugated system 5 in a highly
efficient manner. It should be mentioned that the gram-scale
reaction of 2b still provided good yield. Similarly, a thiophene
substituted polyfluoroarene 6 can also be obtained by Pd-
catalyzed dehydrogenative cross-coupling.2e This strategy
provides an efficient protocol to access diversified polyfluor-
oarene-thiophene structure, a class of important fluorinated
compounds in electronic devices.
Although the exact mechanism of the reaction is still not
clear, on the basis of the results reported by others,2a,b,10,11
a
plausible mechanism is proposed and shown in Scheme 3. An
Scheme 3. Plausible Mechanism of the Pd-Catalyzed Direct
Benzylation of Polyfluoroarenes
2,3,4,5,6-Pentafluoro-4′-methyl-1,1′-biphenyl (3a). The prod-
uct (209 mg, 90% yield) as a white solid (111−113 °C) was purified
with silica gel chromatography (petroleum ether). This compound is
known. 1H NMR (300 MHz, CDCl3) δ 7.31 (s, 4H), 2.42 (s, 3H). 19
F
NMR (282 MHz, CDCl3) δ −143.8 (dd, J = 22.4, 8.0 Hz, 2F), −157.7
(t, J = 20.3 Hz, 1F), −163.8 (td, J = 22.4, 8.0 Hz, 2F). [lit.2a 1H NMR
(300 MHz, CDCl3) δ 7.31 (s, 4H), 2.42 (s, 3H). 19F NMR (282 MHz,
CDCl3) δ −164.6 to −164.3 (m, 2F), −158.1 (t, J = 21.0 Hz, 1F),
−145.4 (dd, J = 23.0, 7.6 Hz, 2F)]; MS (EI) m/z (%) 258 (M+, 100),
237.
2,3,4,5,6-Pentafluoro-4′-methoxy-1,1′-biphenyl (3b). The
product (224 mg, 91% yield) as a white solid (114−116 °C) was
purified with silica gel chromatography (petroleum ether/diethyl ether
= 100:1). This compound is known.1H NMR (300 MHz, CDCl3) δ
7.37 (d, J = 7.2 Hz, 2H), 7.02 (d, J = 7.2 Hz, 2H), 3.87 (s, 3H). 19F
NMR (282 MHz, CDCl3) δ −143.4 (dd, J = 22.8, 8.0 Hz, 2F), −156.3
(t, J = 21.4 Hz, 1F), - 162.3 (td, J = 22.9, 9.0 Hz, 2F). [lit.2a 1H NMR
(300 MHz, CDCl3) δ 7.33−7.38 (m, 2H), 6.98−7.04 (m, 2H), 3.86 (s,
3H). 19F NMR (282 MHz, CDCl3) δ −145.7 (dd, J = 23.0, 7.6 Hz,
2F), −158.5 (t, J = 21.0 Hz, 1F), −164.7 to −164.3 (m, 2F)]; MS (EI)
m/z (%) 274 (M+, 100), 231.
5-(Perfluorophenyl)benzo[d][1,3]dioxole (3c). The product
(228 mg, 88% yield) as a white solid (95−98 °C) was purified with
silica gel chromatography (petroleum ether/diethyl ether = 100:1).
1
This compound is known. H NMR (300 MHz, CDCl3) δ 6.95−6.88
oxidative addition of aryl iodides 2 to a zero valent Pd species is
envisioned to take place as an initial step leading to a Pd-aryl
intermediate I. After the silver salt abstracts iodide ligand from
the palladium(II) complex I, a palladium complex II would be
generated. Complex II subsequently goes through the
concerted metalation-deprotonation (CMD) process11 to
form III. As the final step of the catalytic cycle, reductive
elimination of III produces polyfluoaryl-aryls upon the
regeneration of Pd(0) species.
In conclusion, we have developed a mild reaction (70 °C) for
Pd-catalyzed direct arylation of polyfluoroarenes with aryl
iodides. The reaction makes use of inexpensive PPh3 as ligand
and pure water as reaction medium and affords high yields and
excellent functional group compatibility, which provides a
convenient protocol for the preparation of polyfluoaryl-aryls of
interest in functional materials and life science.
(m, 3H), 6.05 (s, 2H). 19F NMR (282 MHz, CDCl3) δ −143.6 (m,
2F), −156.3 (t, J = 19.7, 1F), −162.6 (m, 2F). [lit.12 1H NMR (400
MHz, CDCl3) δ 6.95−6.88 (m, 3H), 6.04 (s, 2H). 19F NMR (377
MHz, CDCl3) δ −143.2 (dd, J = 23.4, 8.3 Hz, 2F, 2F), −156.0 (t, J =
20.7, 1F), −162.3 (m, 2F)]; MS (EI) m/z (%) 288 (M+), 248 (100).
2,3,4,5,6-Pentafluoro-1,1′:4′,1″-terphenyl (3d). The product
(236 mg, 82% yield) as a white solid (186−188 °C) was purified with
silica gel chromatography (petroleum ether). This compound is
known. 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.65
(d, J = 8.1 Hz, 2H), 7.53−7.42 (m, 4H), 7.40−7.37 (m, 1H). 19F NMR
(282 MHz, CDCl3) δ −143.6 (dd, J = 22.5, 8.0 Hz, 2F), −157.2 (t, J =
20.4 Hz, 1F), −163.4 (td, J = 22.5, 8.1 Hz, 2F). [lit.12,13 1H NMR (400
MHz, CDCl3) δ 7.71−7.74 (m, 2H), 7.64−7.66 (m, 2H), 7.52−7.46
(m, 4H), 7.42−7.38 (m, 1H). 19F NMR (377 MHz, CDCl3) δ −143.1
(dd, J = 23.0, 8.3 Hz, 2F), −155.5 (t, J = 20.7 Hz, 1F), −162.2 (m,
2F)]; MS (EI) m/z (%) 320 (M+, 100).
2,3,4,5,6-Pentafluoro-4′-nitro-1,1′-biphenyl (3e). The product
(237 mg, 91% yield) as a yellow solid (86−88 °C) was purified with
silica gel chromatography (petroleum ether/EtOAc = 50:1). This
1
EXPERIMENTAL SECTION
compound is known. H NMR (300 MHz, CDCl3) δ 8.37 (d, J = 8.7
■
Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H). 19F NMR (282 MHz, CDCl3) δ
−142.3 (dd, J = 22.2, 7.8 Hz, 2F), −152.3 (t, J = 20.8 Hz, 1F), −160.5
(m, 2F). [lit.14 1H NMR (300 MHz, CDCl3) δ 8.35−8.39 (m, 2H),
7.61−7.66 (m, 2H). 19F NMR (282 MHz, CDCl3) δ −143.7 (dd, J =
General Procedure for Pd-Catalyzed Direct Arylation of
Polyfluoroarenes with Aryl Iodides on Water. To a septum-
capped 25 mL Schlenck tube were added Pd(OAc)2 (5 mol %), PPh3
(10 mol %), Ag2CO3 (0.75 equiv), and aryl iodide (0.9 mmol, 1.0
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21.2, 8.9 Hz, 2F), −153.6 (t, J = 20.9 Hz, 1F), −161.9 (m, 2F)]; MS
(EI) m/z (%) 289 (M+, 100), 242, 231, 224, 193.
was purified with silica gel chromatography (petroleum ether/EtOAc
= 50:1). 1H NMR (300 MHz, CDCl3) δ 7.36 (s, 4H), 2.44 (s, 3H). 19
F
Ethyl 2′,3′,4′,5′,6′-Pentafluoro-[1,1′-biphenyl]-3-carboxy-
late (3f). The product (273 mg, 96% yield) as a light green solid
(54−56 °C) was purified with silica gel chromatography (petroleum
NMR (282 MHz, CDCl3) δ −134.7 (m, 2F), −141.34 (m, 2F). 13C
NMR (100 MHz, CDCl3) δ 147.5 (dm, J = 260.5 Hz), 143.8 (dm, J =
249.0 Hz), 140.8, 129.8, 129.6, 127.3 (t, J = 16.5 Hz), 122.7, 107.6,
92.4 (m), 21.4. IR (thin film) νmax 2247, 1485 cm−1. MS (EI) m/z (%)
265 (M+, 100), 244. HRMS: calcd for C14H7F4N 265.0514, found
265.0514.
1
ether/EtOAc = 50:1). H NMR (300 MHz, CDCl3) δ 8.17−8.12 (m,
2H), 7.61−7.59 (m, 2H), 4.41 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz,
3H). 19F NMR (282 MHz, CDCl3) δ −142.5 (dd, J = 22.5, 7.9 Hz,
2F), −154.2 (t, J = 20.9 Hz, 1F), −161.3 (td, J = 22.5, 8.0 Hz, 2F). 13C
NMR (100 MHz, CDCl3) δ 165.7, 144.1 (dm, J = 247.2 Hz), 140.6
(dm, J = 253.2 Hz), 137.8 (dm, J = 251.5 Hz), 134.3, 131.2, 130.3,
128.8, 126.7, 115.0 (m), 61.2, 14.2. IR (thin film) νmax 1716 cm−1. MS
(EI) m/z (%) 316 (M+), 288, 271 (100). Anal. Calcd. for C15H9F5O2:
C, 56.97; H, 2.87; Found: C, 56.82; H, 2.82.
2,3,5,6-Tetrafluoro-4′-methyl-4-(trifluoromethyl)-1,1′-bi-
phenyl (3m). The product (236 mg, 85% yield) as a white solid
(111−114 °C) was purified with silica gel chromatography (petroleum
1
ether/diethyl ether = 100:1). This compound is known. H NMR
(300 MHz, CDCl3) δ 7.43−7.36 (m, 4H), 2.48 (s, 3H). 19F NMR
(282 MHz, CDCl3) δ −56.4 (m, 3F), −141.2 (m, 2F), −141.9 (m,
2F). [lit.15 1H NMR (400 MHz, CDCl3) δ 7.39 (m, 4H), 2.49 (s, 3H).
19F NMR (377 MHz, CDCl3) δ −56.17 (t, J = 21.5 Hz, 3F), −140.96
(m, 2F), −141.68 (m, 2F)]; MS (EI) m/z (%) 308 (M+, 100), 219.
4-Bromo-2,3,5,6-tetrafluoro-4′-methoxy-1,1′-biphenyl (3n).
The product (standard conditions: 142 mg, 47% yield; using DMF as
solvent: 236 mg, 78% yield) as a white solid (117−119 °C) was
purified with silica gel chromatography (petroleum ether/diethyl ether
2,3,4,4′,5,6-Hexafluoro-1,1′-biphenyl (3g). The product (172
mg, 73% yield) as a white solid (112−114 °C) was purified with silica
1
gel chromatography (petroleum ether). This compound is known. H
NMR (300 MHz, CDCl3) δ 7.39 (m, 2H), 7.22 (m, 2H). 19F NMR
(282 MHz, CDCl3) δ −111.7 (s, 1F), −143.7 (dd, J = 22.5 Hz, 7.9 Hz,
2F), −155.5 (t, J = 20.0 Hz, 1F), −162.3 (td, J = 22.5, 7.9 Hz, 2F).
[lit.2c 1H NMR (300 MHz, CDCl3) δ 7.36−7.45 (m, 2H), 7.14−7.24
(m, 2H). 19F NMR (282 MHz, CDCl3) δ −113.3 (s, 1F), −142.1 (dd,
J = 23.0 Hz, 7.6 Hz, 2F), −157.2 (t, J = 21.0 Hz, 1F), −163.8 to
−164.1 (m, 2F) ]; MS (EI) m/z (%) 262 (M+, 100), 242.
1
= 100:1). H NMR (300 MHz, CDCl3) δ 7.41 (d, J = 8.4 Hz, 2H),
7.02 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H). 19F NMR (282 MHz, CDCl3) δ
−133.6 (m, 2F), −142.1 (dd, J = 22.6, 9.0 Hz, 2F). 13C NMR (100
MHz, CDCl3) δ 160.3, 145.3 (dm, J = 246.1 Hz), 144.1 (dm, J = 248.0
Hz), 131.3, 120.0 (t, J = 16.6 Hz), 118.9, 114.2, 97.9 (t, J = 22.5 Hz.),
55.3. IR (thin film) νmax 1479 cm−1. MS (EI) m/z (%) 336, 334 (M+,
100), 292, 291. Anal. Calcd for C13H7BrF4O: C, 46.60; H,2.11. Found:
C, 46.93; H, 2.15.
4′-Bromo-2,3,4,5,6-pentafluoro-1,1′-biphenyl (3h). The prod-
uct (241 mg, 83% yield) as a white solid (81−83 °C) was purified with
silica gel chromatography (petroleum ether). This compound is
known. 1H NMR (300 MHz, CDCl3) δ 7.64 (d, J = 8.1 Hz, 2H), 7.31
(d, J = 8.1 Hz, 2H). 19F NMR (282 MHz, CDCl3) δ −143.51 (dd, J =
22.3, 7.7 Hz, 2F), −154.99 (t, J = 21.1 Hz, 1F), −162.0 (td, J = 22.3,
8.7 Hz, 2F). [lit.9 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J = 8.5 Hz,
2H), 7.31 (d, J = 8.5 Hz, 2H). 19F NMR (282 MHz, CDCl3) δ
−143.52 (m, 2F), −155.09 (m, 1F), −162.54 (m, 2F)]; MS (EI) m/z
(%) 324, 322 (M+, 100), 242.
2,3,5,6-Tetrafluoro-4-(p-tolyl)pyridine (3o). The product (186
mg, 86% yield) as a white solid (94−96 °C) was purified with silica gel
chromatography (petroleum ether/diethyl ether = 100:1). This
1
compound is known. H NMR (300 MHz, CDCl3) δ 7.42 (d, J =
7.2 Hz, 2H), 7.34 (d, J = 7.2 Hz, 2H), 2.44 (s, 3H). 19F NMR (282
MHz, CDCl3) δ −91.4 (m, 2F), −145.7 (m, 2F). [lit.2c 1H NMR (400
MHz, CDCl3) δ 7.42 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H),
2.43 (s, 3H). 19F NMR (377 MHz, CDCl3) δ −96.1 to −96.3 (m, 2F),
−150.3−150.5 (m, 2F)]; MS (EI) m/z (%) 241 (M+, 100), 220.
2,3,5,6-Tetrafluoro-4′-methoxy-4-methyl-1,1′-biphenyl (3p).
The product (189 mg, 78% yield) as a white solid (116−118 °C) was
purified with silica gel chromatography (petroleum ether/diethyl ether
3-(Perfluorophenyl)thiophene (3i). The product (Standard
conditions: 90 mg, 40% yield; using DMF as solvent: 158 mg, 70%
yield) as a white solid (41−43 °C) was purified with silica gel
chromatography (petroleum ether/diethyl ether = 100:1). This
1
compound is known. H NMR (300 MHz, CDCl3) δ 7.66 (s, 1H),
7.47 (m, 1H), 7.36 (m, 1H). 19F NMR (282 MHz, CDCl3) δ −142.4
(dd, J = 22.3, 7.4 Hz, 2F), −156.6 (t, J = 21.0 Hz, 1F), −162.6 (td, J =
22.3, 7.8 Hz, 2F). [lit.2c 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H),
7.44−7.46 (m, 1H), 7.35−7.36 (m, 1H). 19F NMR (377 MHz,
CDCl3) δ −142.0 (dd, J = 22.2, 7.9 Hz, 2F), −156.4 (t, J = 20.7 Hz,
1F), −162.5 (m, 2F)]; MS (EI) m/z (%) 250 (M+, 100).
1
= 100:1). This compound is known. H NMR (300 MHz, CDCl3) δ
7.39 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 3.86 (s, 3H), 2.31
(s, 3H). 19F NMR (282 MHz, CDCl3) δ −144.8 (dd, J = 22.8 Hz, 10.1
Hz, 2F), −146.4 (dd, J = 22.8, 13.8 Hz, 2F). [lit.12 1H NMR (400
MHz, CDCl3) δ 7.39 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H),
3.86 (s, 3H), 2.31 (t, J = 2.0 Hz, 3H). 19F NMR (377 MHz, CDCl3) δ
−144.4 (dd, J = 22.6 Hz, 12.8 Hz, 2F), −146.0 (dd, J = 22.2, 12.4 Hz,
2F)]; MS (EI) m/z (%) 270 (M+, 100), 255, 227.
2,4,6-Trifluoro-4′-methoxy-1,1′-bipheny (3q). Four equiva-
lents of fluoroarene was used. The product (113 mg, 78% yield) as
a white solid (94−96 °C) was purified with silica gel chromatography
(petroleum ether/diethyl ether = 100:1). This compound is known.
1H NMR (300 MHz, CDCl3) δ 7.36 (d, J = 8.1 Hz, 2H), 7.00 (d, J =
8.1 Hz, 2H), 6.75 (t, J = 8.1 Hz, 2H). 3.86 (s, 3H). 19F NMR (282
MHz, CDCl3) δ −110.4 (m, 1F), −112.1 (m, 2F). [lit.12 1H NMR
(400 MHz, CDCl3) δ 7.35 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz,
2H), 6.74 (t, J = 8.4 Hz, 2H). 3.85 (s, 3H). 19F NMR (377 MHz,
CDCl3) δ −109.9 (t, J = 5.6 Hz, 1F), −111.6 (d, J = 5.6 Hz, 2F)]; MS
(EI) m/z (%) 238 (M+, 100), 223, 195.
2,6-Difluoro-4′-methoxy-3-nitro-1,1′-biphenyl (3r). Four
equivalents of fluoroarene was used. The product (standard
conditions: 57 mg, 36% yield; using DMF as solvent: 123 mg, 78%
yield) as a light green solid (96−98 °C) was purified with silica gel
chromatography (petroleum ether/EtOAc = 50:1). 1H NMR (300
MHz, CDCl3) δ 8.08 (m, 1H), 7.40 (d, J = 8.7 Hz, 2H), 7.11 (t, J = 8.4
Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H) . 19F NMR (282 MHz,
CDCl3) δ −101.9 (m, 1F), −116.4 (dd, J = 15.0, 8.2 Hz, 1F). 13C
NMR (100 MHz, CDCl3) δ 162.8 (dd, J = 257.0, 6.1 Hz), 160.2, 153.9
(dd, J = 264.2, 7.9 Hz), 134.8, 131.5, 125.5 (d, J = 11.1 Hz), 120.8 (t, J
2,3,5,6-Tetrafluoro-4′-methoxy-1,1′-biphenyl (3j). 4.0 equiv
of fluoroarene was used. The product (132 mg, 86% yield) as a white
solid (97−100 °C) was purified with silica gel chromatography
(petroleum ether/diethyl ether = 100:1). This compound is known.
1H NMR (300 MHz, CDCl3) δ 7.40 (s, 2H), 7.01 (m, 3H), 3.86 (s,
3H). 19F NMR (282 MHz, CDCl3) δ −140.1 (m, 2F), −144.5 (m,
2F). [lit.12 1H NMR (400 MHz, CDCl3) δ 7.39−7.42 (m, 2H), 6.98−
7.06 (m, 3H), 3.87 (s, 3H). 19F NMR (377 MHz, CDCl3) δ −139.5
(dd, J = 13.2, 23.0 Hz, 2F), −144.3 (dd, J = 23.0, 13.6 Hz, 2F)]; MS
(EI) m/z (%) 256 (M+, 100), 213.
2,3,4,6-Tetrafluoro-4′-methoxy-1,1′-biphenyl (3k). 4.0 equiv
of fluoroarene was used. The product (Standard conditions: 94 mg,
61% yield; using DMF as solvent: 117 mg, 76% yield) as a white solid
(72−74 °C) was purified with silica gel chromatography (petroleum
ether/diethyl ether = 100:1). 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J
= 8.1 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 6.85 (m, 1H), 3.86 (s, 3H).
19F NMR (282 MHz, CDCl3) δ −118.9 (t, J = 9.8 Hz, 1F), −134.5 (m,
1F), −136.2 (d, J = 22.5 Hz, 1F), −165.3 (m, 1F). 13C NMR (75.4
MHz, CDCl3) δ 159.8, 154.2 (dm, J = 246.1 Hz), 149.4 (dm, J = 248.7
Hz), 148.9 (dm, J = 247.8 Hz), 137.5 (dm, J = 252.7 Hz), 131.3, 119.5,
115.6 (m), 113.9, 100.7 (m), 55.2. IR (thin film) νmax 1507 cm−1. MS
(EI) m/z (%) 256 (M+, 100), 241, 213. HRMS calcd for C13H8F4O:
256.0511; Found: 256.0508.
2,3,5,6-Tetrafluoro-4′-methyl-[1,1′-biphenyl]-4-carbonitrile
(3l). The product (205 mg, 86% yield) as a white solid (150−152 °C)
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The Journal of Organic Chemistry
Note
= 18.2 Hz), 118.8, 114.1, 112.0 (dd, J = 25.2, 4.1 Hz), 55.3. IR (thin
film) νmax 1519 cm−1. MS (EI) m/z (%) 265 (M+, 100), 219, 175.
HRMS calcd for C13H9F2NO3 265.0550, found 265.0552. Anal. Calcd
for C13H9F2NO3: C, 58.87; H, 3.42. Found: C, 58.86; H, 3.42.
(E)-tert-Butyl 3-(2,3,5,6-tetrafluoro-4′-methoxy-[1,1′-bi-
phenyl]-4-yl)acrylate (5). To a septum-capped 25 mL sealed tube
were added Pd(OAc)2 (10 mol %), 3j (0.3 mmol), and Ag2CO3 (2.0
equiv) under N2, followed by alkene (2.0 equiv), PivOH (3.0 equiv),
and DMF (2.0 mL). The reaction mixture was warmed to 120 °C (oil
bath) and stirred for 10 h. The reaction was cooled to room
temperature, and EtOAc (80 mL) and water (40 mL) were added. The
organic layer was separated, and the aqueous phase was extracted with
EtOAc (40 mL × 2). The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was
purified by column chromatography (petroleum ether/EtOAc = 50:1)
to give 5 (76 mg, 66% yield, E/Z = 15:1, determined by 19F NMR) as
a yellow-green solid. Mp 247−249 °C; 1H NMR (300 MHz, CDCl3) δ
7.66 (d, J = 16.5 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.03 (d, J = 8.3 Hz,
2H), 6.73 (d, J = 16.5 Hz, 1H), 3.87 (s, 3H), 1.56 (s, 9H). 19F NMR
(282 MHz, CDCl3) δ −140.6 (dd, J = 20.8, 11.5 Hz, 2F), −144.3 (dd,
J = 21.2, 12.2 Hz, 2F). 13C NMR (100 MHz, CDCl3) δ 165.5, 160.3,
145.6 (dm, J = 247.6 Hz), 143.9 (dm, J = 244.2 Hz), 131.4, 128.2,
127.8 (t, J = 8.6 Hz), 119.0, 114.1, 114.0, 112.7(m), 81.2, 55.3, 28.0. IR
(thin film) νmax 1716, 1480 cm−1. MS (EI) m/z (%) 382 (M+), 326
(100), 309. HRMS calcd for C20H18F4O3 382.1192, found 382.1188.
N,N-Dimethyl-5-(2,3,5,6-tetrafluoro-4′-methoxy-[1,1′-bi-
phenyl]-4-yl)thiophene-2-carboxamide (6). To a septum-capped
25 mL sealed tube were added Pd(OAc)2 (10 mol %), 3j (2.0 equiv),
N,N-dimethylthiophene-2-carboxamide (0.3 mmol) and Ag2CO3 (1.5
equiv) under N2, followed by DMSO (0.1 mL) and DMF (1.9 mL).
The reaction mixture was warmed to 120 °C (oil bath) and stirred for
10 h. The reaction was cooled to room temperature, and EtOAc (80
mL) and water (40 mL) were added. The organic layer was separated,
and the aqueous phase was extracted with EtOAc (40 mL × 2). The
combined organic layers were dried over anhydrous Na2SO4, filtered,
and concentrated. The residue was purified by column chromatog-
raphy (petroleum ether/EtOAc = 50:1) to give desired product (60
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1
mg, 49% yield) as a yellow-green solid. Mp 155−157 °C; H NMR
(300 MHz, CDCl3) δ 7.56 (d, J = 3.6 Hz, 1H), 7.46 (d, J = 8.7 Hz,
2H), 7.42 (d, J = 3.6 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H),
3.23 (s, 6H). 19F NMR (282 MHz, CDCl3) δ −140.0 (dd, J = 21.6,
11.0 Hz, 2F), −144.1 (dd, J = 21.6, 11.3 Hz, 2F). 13C NMR (100
MHz, CDCl3) δ 163.8, 160.3, 144.3 (dm, J = 244.7 Hz), 143.8 (dm, J
= 248.9 Hz), 139.9 (t, J = 3.9 Hz), 131.4, 131.1, 129.5 (t, J = 5.9 Hz),
129.1, 119.4 (t, J = 16.4 Hz), 119.2, 114.2, 111.9 (t, J = 14.6 Hz), 55.3.
IR (thin film) νmax 1599, 1468 cm−1. MS (EI) m/z (%) 409 (M+), 365
(100), 293. HRMS calcd for C20H15F4NSO2 409.0760, found
409.0764.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Detailed experimental procedures and characterization data for
new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: xgzhang@mail.sioc.ac.cn.
Notes
The authors declare no competing financial interest.
(10) Guo, P.; Joo, J. M.; Rakshit, S.; Sames, D. J. Am. Chem. Soc.
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ACKNOWLEDGMENTS
■
The National Basic Research Program of China (973 program
(No 2012CB821600)), the NSFC (Nos 20902100, 20832008,
21172242), and SIOC are greatly acknowledged for funding
this work.
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Note
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