Palladium-catalyzed desulfitative direct C-H arylation of electron-deficient polyfluoroarenes with sodium arenesulfinates

Article abstract of DOI:10.1002/adsc.201300587

The palladium-catalyzed direct arylation of electron-deficient polyfluorobenzenes was developed in the presence of silver carbonate and trisodium phosphate. This protocol allowed use of both electron- deficient and electron-rich aromatic sulfinic acid sodium salts as arylating reagents for the direct arylation of a variety of polyfluoroarenes to produce fluorobiaryls in good to excellent yields, providing a complement to the existing methods for the direct arylation of polyfluoroarenes.

Full text of DOI:10.1002/adsc.201300587

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DOI: 10.1002/adsc.201300587
À
Palladium-Catalyzed Desulfitative Direct C H Arylation of
Electron-Deficient Polyfluoroarenes with Sodium Arenesulfinates
Tao Miaoa and Lei Wanga,b,*
a
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, Peopleꢀs Republic of China
Fax : (+86)-561-309-0518; phone: (+86)-561-380-2069; e-mail: leiwang@chnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, Peopleꢀs
b
Republic of China
Received: July 3, 2013; Revised: September 30, 2013; Published online: December 6, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300587.
Abstract: The palladium-catalyzed direct arylation of fluorobiaryls in good to excellent yields, providing
electron-deficient polyfluorobenzenes was developed a complement to the existing methods for the direct
in the presence of silver carbonate and trisodium arylation of polyfluoroarenes.
phosphate. This protocol allowed use of both elec-
À
tron-deficient and electron-rich aromatic sulfinic acid Keywords: desulfitative reaction; direct C H aryla-
sodium salts as arylating reagents for the direct ary- tion; palladium; polyfluoroarenes; sodium arenesul-
lation of a variety of polyfluoroarenes to produce finates
Introduction
matic benzoic acids.[5] Subsequently, Su and Shi et al.
have independently reported the noteworthy new de-
Biaryls containing polyfluoroarene structural moieties velopment of polyfluoroarenes coupled with non-acti-
have demonstrated importance in medicinal chemistry vated ꢁsimpleꢀ arenes in the presence of PdACTHUNTRGNE(UNG OAc)2 to
and numerous functional materials such as electron form fluorinated biaryls.[6] Although remarkable ad-
transport devices and organic light emitting diodes.[1] vances in these types of transformations have been
Generally, the preparation of these structural units achieved, to develop new and reliable alternative
often requires the use of pentafluorophenyl organo- direct arylation of polyfluoroarenes remains highly
metallics (copper species, stannanes, boronic acids desirable from both scientific and practical points of
and benzoates) to react with electrophiles like aryl view.
À
halides through traditional cross-coupling methodolo-
Palladium-catalyzed desulfitative C C bond form-
gy.[2] While these methods have been generally versa- ing reactions via release of SO2 provide another
tile and used extensively, this “prefunctionalization” promising access to complex molecules, in which aro-
process is non-trivial and suffers from the tedious syn- matic sulfinic acids (or salts) are used as complemen-
thetic steps for the preparation of the organometallic tary arylating reagents to aryl halides or expensive or-
reagents, the incompatibility of important functional ganometallics in traditional cross-coupling reactions.
groups and the use of toxic substrates (stannanes). In Since aromatic sulfinic acids (or salts) are compara-
the past few years, significant progress has been made tively stable, easy to handle, and accessible prepara-
À
in the transition metal-catalyzed direct C H arylation tively from their corresponding sulfonyl chlorides, the
of polyfluoroarenes, which not only represents a more desulfitative cross-coupling reactions have attracted
efficient synthetic route to the polyfluoroaryl-aryls, considerable interest in recent years. As a result, suc-
but also in some cases offers a solution to the prob- cesses in desulfitative cross-coupling of aromatic sul-
lem arising from the use of oxygen- and moisture-sen- finic acids (or salts) with olefins, nitriles or aldehydes
sitive or precious organometallic reagents.[3–6] In this have been accomplished by using Pd/Cu, Pd/O2, Pd
À
regard, the elegant work by Fagnou displayed that C
and Rh catalysts,[7] and the desulfitative coupling re-
H bonds of polyfluorobenzenes could be arylated actions between sodium arenesulfinates and different
with aryl halides or phenyl triflates under palladium electrophiles have been also established.[8] Very re-
catalysis.[4] After that, Su and co-works disclosed cently, such catalytic methods have been extended to
À
a Pd-catalyzed direct arylation of electron-deficient the direct C H arylation of heteroaromatics, which
polyfluoroarenes with organoboron reagents and aro- has further highlighted the great potential of sodium
Adv. Synth. Catal. 2014, 356, 429 – 436
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Tao Miao and Lei Wang
Scheme 1.
arenesulfinates to serve as versatile starting materials Results and Discussion
for the construction of aryl-substituted compounds.[9]
Yet, general methodologies for the direct coupling of In our initial study, we chose benzenesulfinic acid
sodium arenesulfinates with fluorinated aromatics are sodium (1a) and pentafluorobenzene (2a) as model
scarce. Herein, we wish to report a palladium-cata- substrates to optimize the reaction conditions with
lyzed direct arylation of electron-deficient polyfluoro- different catalysts, oxidants and solvents (Table 1).
À
ACHTUNGTRENNUNGarenes with sodium arylsulfinates via C H activation When PdAHCUTNGTREN(NUNG OAc)2 was used as the catalyst with
under mild conditions (Scheme 1).
Ag2CO3 as oxidant, Na3PO4·12H2O as additive and
mixture of DMSO and H2O (3:1) as the solvent, the
reaction of 1a with 2a gave the desulfitative arylated
product (3a) in 66% yield (Table 1, entry 1). Mean-
while, arylation also proceeded in comparable yield
Table 1. Palladium-catalyzed desulfitative direct arylation of pentafluorobenzene with sodium benzenesulfinate under vari-
ous conditions.[a]
Entry
Pd source
Pd(OAc)2
Oxidant
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
G
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOAc
Ag2O
AgSbF6
CuACTHNGURETNNU(G OAc)2
K2S2O8
BQ
TBHP
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMA/H2O (3:1)
DMF/H2O (3:1)
NMP/H2O (3:1)
66
61
86
80
72
27
46
35
10
16
0
0
0
37
8
0
Pd(OCOCF3)2
PdCl2
Pd(CH3CN)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)4
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
9
10
11
12
13
14
15
16
17
18
19[c]
20[d]
21[e]
DMSO/H2O (1:1)
DMSO/H2O (6:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
51
58
64
60
31
[a]
Reaction conditions: 1a (0.40 mmol), 2a (0.25 mmol) and Pd catalyst (7 mol%), oxidants (0.40 mmol), Na3PO4·12H2O
(0.45 mmol), in DMSO/H2O (3:1, 2.0 mL), 1008C for 18 h.
Isolated yield.
5 mol% PdCl2 was used.
Reaction for 10 h.
[b]
[c]
[d]
[e]
In the absence of Na3PO4·12H2O.
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Desulfitative Direct C H Arylation of Electron-Deficient Polyfluoroarenes
Table 2. Palladium-catalyzed desulfitative direct arylation of
and efficiency in the presence of PdACTHNUGRTNEUNG(OCOCF3)2
pentafluorobenzene with various arylsulfinic acid sodiums.[a]
(Table 1, entry 2 vs. 1). To our delight, PdCl2 showed
excellent activity and the desired product (3a)
was isolated in 86% yield (Table 1, entry 3).
Pd
catalysts and generated 3a in good yields (Table 1, en-
tries 4 and 5). However, Pd(PPh3)4 was not beneficial
ACHTUNGTRENNUNG(CH3CN)2Cl2 and PdACHTUNGTREN(NNGU PPh3)2Cl2 were also effective
AHCTUNGTRENNUNG
for the catalytic reaction and lower a yield was ob-
tained (Table 1, entry 6). Further exploration of oxi-
dants in the model reaction indicated that Ag2CO3
was superior to the others, the inorganic oxidants in-
cluding AgOAc, Ag2O, AgSbF6 and CuACTHNUTRGNEN(UG OAc)2 gave
the inferior results and led to the formation of prod-
uct (3a) in 10–46% yields (Table 1, entries 7–10).
However, K2S2O8 did not work in the model reaction
(Table 1, entry 11). Under the present reaction condi-
tions, the organic oxidants, BQ and TBHP were also
examined and were harmful to this transformation
(Table 1, entries 12 and 13). The influence of solvents
was also investigated. A mixture of DMSO and H2O
(3:1) was optimal, it is supposed that DMSO might
serve as a ligand to activate the Pd catalyst and pre-
vent the formation of palladium black.[3a,6b,10] The
yield decreased sharply when the reaction was carried
out in a mixture of DMA and H2O (3:1) (Table 1,
entry 14). The other solvents such as mixtures of
DMF or NMP and H2O showed very poor perfor-
mance and this reaction almost completely suppressed
(Table 1, entries 15 and 16). The amount of water has
an obvious effect on this reaction, lower yields were
obtained when the DMSO/H2O ratio was changed
from 3:1 to 1:1 and 6:1 (Table 1, entries 17 and 18).
Subsequently, when the catalyst was reduced to
5 mol%, the reaction only afforded the desired prod-
uct in 64% yield (Table 1, entry 19). On shortening
the reaction time to 10 h, the cross-coupling reaction
of 1a with 2a produced a 60% yield under otherwise
identical conditions (Table 1, entry 20). Furthermore,
removal of the Na3PO4·12H2O additive afforded
a poor result of 31%, suggesting that this additive was
an essential component for this arylated reaction
(Table 1, entry 21).
Based on the optimized reaction conditions
(7 mol% of PdCl2, 1.6 equiv. of Ag2CO3, 1.8 equiv. of
Na3PO4·12H2O, 2.0 mL of a 3:1 mixture of DMSO
and H2O, 1008C, 18 h), the scope and limitation of
the Pd-catalyzed desulfitative direct arylation of poly-
fluorobenzene reaction was examined. As can be seen
from Table 2, the reactions of a wide range of sodium
arenesulfinates with pentafluorobenzene could pro-
ceed well and generate the desired arylated products
in good to excellent yields. The substituted benzene-
sulfinic acid sodium salts with electron-donating
groups, such as methyl, tert-butyl and methoxy react-
ed with pentafluorobenzene efficiently and afforded
the corresponding arylated products 3a–3e in 71%–
91% yields (Table 2, entries 1–5). Meanwhile, this re-
[a]
Reaction conditions: 1 (0.40 mmol), 2a (0.25 mmol) and
PdCl2 (7 mol%), Ag2CO3 (0.40 mmol), Na3PO4·12H2O
(0.45 mmol), in DMSO/H2O (3:1, 2.0 mL), 1008C for
18 h.
Isolated yields.
Solvent (4.0 mL) was used.
[b]
[c]
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Tao Miao and Lei Wang
Table 3. Palladium-catalyzed desulfitative direct arylation of polyfluorobenzenes with aryl-
sulfinic acid sodiums.[a]
[a]
Reaction conditions: 1 (0.40 mmol), 2 (0.25 mmol) and PdCl2 (7 mol%), Ag2CO3
(0.40 mmol), Na3PO4·12H2O (0.45 mmol), in DMSO/H2O (3:1, 2.0 mL), 1008C for 18 h.
Isolated yields.
1,3,5-Trifluorobenzene (3 equiv.) was used.
[b]
[c]
action is also tolerant of electron-withdrawing fluoro, Table 3. Under the standard conditions, tetrafluoro-
chloro, bromo and nitro substituents in the aromatic and trifluorobenzenes can be selectively cross-arylat-
ring of sodium arenesulfinates and arylated products ed with sodium arenesulfinates. For example, 2,3,5,6-
3f, 3g, 3h and 3i were observed in 90%, 82%, 75%, tetrafluorotoluene,
2,3,5,6-tetrafluoroanisole
and
83% yields, respectively (Table 2, entries 6–9). It is 2,3,5,6-tetrafluorobenzotrifluoride effectively under-
important to note that chloro- and bromo-substituted went direct arylation with good yields obtained (3l–
sodium arenesulfinates selectively underwent the de- w). However, these reaction conditions are not suita-
sulfitative arylation, which may allow for further syn- ble for 2,3,5,6-tetrafluoropyridine, which participated
thetic transformations by transition metal-catalyzed in the reaction with benzenesulfinic acid sodium to
coupling and other reactions. Moreover, the more furnish the corresponding products 3s, displaying
bulky 2-naphthalenesulfinic acid sodium salt (1j) was 45% yield. Maybe the substrate coordinated with the
a good substrate for this arylation reaction as shown palladium catalyst and so reduced the catalyst effi-
for the the successful formation of 3j in 77% yield ciency. Gratifyingly, although 1,2,4,5-tetrafluoroben-
under the present reaction conditions (Table 2, zene and 1,3,5-trifluorobenzene have more than one
entry 10). However, this reaction was extremely sensi- potential site for reaction, the reactions of these poly-
tive to steric hindrance. For example, when sodium fluorobenzenes mainly generated the monoarylated
arenesulfinate bearing an ortho-substitutent (sodium product. 1,2,4,5-Tetrafluorobenzene underwent the re-
2-methylbenzenesulfinate, 1k) was treated with penta- actions smoothly and monoarylated products (3t–3w)
fluorobenzene, no desired product 3k was obtained, were achieved in 74%–80% yields.
in agreement with the observations by Su[5a,6a] and
Shi[6b] (Table 2, entry 11).
However, 1,3,5-trifluorobenzene exhibits low reac-
tivity, probably due to the low acidity of the C H
À
The substrate scope with respect to polyfluoroben- bond, and requires 3 equiv. of the fluorobenzene to
zenes was also investigated and is presented in produce 3w in moderate yield.
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Desulfitative Direct C H Arylation of Electron-Deficient Polyfluoroarenes
Experimental Section
General Considerations
1
All H NMR, 13C NMR and 19F NMR spectra were recorded
on a 400 MHz Bruker FT-NMR spectrometer (400 MHz,
100 MHz or 377 MHz, respectively). All chemical shifts are
given as d values (ppm) with reference to tetramethylsilane
(TMS) as an internal standard. The peak patterns are indi-
cated as follows: s, singlet; d, doublet; t, triplet; m, multip-
let; q, quartet. The coupling constants, J, are reported in
Hertz (Hz). The chemicals and solvents were purchased
from commercial suppliers either from Aldrich, USA or
Shanghai Chemical Company, China. Products were purified
by flash chromatography on 100–200 mesh silica gels, SiO2.
À
Typical Procedure for Direct C H Arylation of
Electron-Deficient Polyfluoroarenes with Arene-
sulfinic Acid Sodium Salts
Scheme 2. The proposed reaction mechanism.
The Schlenk tube equipped with a stir bar was charged with
PdCl2 (0.0175 mmol), Ag2CO3 (0.40 mmol), Na3PO4·12H2O
(0.45 mmol), sodium arenesulfinate (0.40 mmol), and a mix-
ture of DMSO and H2O (3:1, 2.0 mL), then polyfluoroarene
(0.25 mmol) was added by syringe. The reaction mixture was
stirred at 1008C for 18 h. Then it was cooled to room tem-
perature, the reaction mixture was diluted with 5.0 mL of
ethyl ether, filtered through a pad of silica gel, followed by
washing the pad of the silica gel with the same solvent
(10.0 mL). The filtrate was washed with water (3ꢃ5.0 mL).
The organic phase was dried over MgSO4, filtered, concen-
trated under reduced pressure to yield the crude product,
which was further purified by flash chromatography on
silica gel with petroleum ether to provide the corresponding
product.
Although the exact mechanism of the reaction is
still not clear, on the basis of the above observations
and the results reported by others,[4a,5,7c,f] a possible re-
action pathway is proposed and shown in Scheme 2.
The first step is reaction of Pd(II) with arenesulfinic
acid sodium salt provides palladium salt A. Then re-
lease of SO2 from complex A is envisioned to take
place leading to ArPd(II), which activates the fluori-
nated arene probably assisted by CO3 or PO4 to
form intermediate B. Reductive elimination from in-
termediate B produces the polyfluoaryl-aryls 3 and
Pd(0) species. Finally, oxidation of Pd(0) species by
Ag(I) regenerates the catalytically active Pd(II) to
finish the catalytic cycle.
2À
3À
Characterization Data for all Products
2,3,4,5,6-Pentafluoro-1,1’-biphenyl (3a):[2d] Yield: 52.5 mg
(86%); colorless solid; 1H NMR (400 MHz, CDCl3): d=
Conclusions
In conclusion, we have demonstrated an efficient pal-
ladium-catalyzed method for the direct arylation of
electron-deficient polyfluorobenzenes with sodium
arenesulfinates. By using PdCl2 as a catalyst, a broad
range of sodium arenesulfinates efficiently underwent
desulfitative coupling with an array of polyfluoroar-
enes in the presence of a stoichiometric amount of
silver salts to generate fluorobiaryls. This new aryla-
tion reaction provides an alternative to the use of or-
ganometallic reagents in the synthesis of perfluoroaryl
molecules and broadens the scope of Pd-catalyzed de-
sulfitative coupling reactions. The investigation of
sodium arenesulfinates as the aryl source in other
coupling reactions is underway.
7.51–4.46 (m, 3H), 7.43–7.41 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=145.5–145.3 (m), 143.0–142.8 (m), 141.8–141.5
(m), 139.1–139.0 (m), 136.8–136.4 (m), 130.2–130.1 (m),
129.3, 128.7, 126.4, 116.2–115.8 (m).
2,3,4,5,6-Pentafluoro-4’-methyl-1,1’-biphenyl
(3b):[2d]
1
Yield: 54.2 mg (84%); colorless solid; H NMR (400 MHz,
CDCl3): d=7.30 (s, 4H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.5–145.3 (m), 143.0–142.9 (m), 141.5–141.4
(m), 139.4, 139.1–138.9 (m), 136.8–136.5 (m), 130.0, 129.4,
123.4, 116.2–115.8 (m), 21.3.
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Tao Miao and Lei Wang
2,3,4,5,6-Pentafluoro-3’-methyl-1,1’-biphenyl
Yield: 58.7 mg (91%); colorless solid; H NMR (400 MHz,
(3c):[2d]
CDCl3): d=7.48 (d, J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=145.4–145.2 (m),
142.9–141.7 (m), 139.3–139.0 (m), 136.8–136.6 (m), 135.6,
131.5–131.4 (m), 129.1, 124.8, 115.0–114.6 (m).
1
4’-Bromo-2,3,4,5,6-pentafluoro-1,1’-biphenyl
(3h):[3b]
1
Yield: 60.6 mg (75%); colorless solid; H NMR (400 MHz,
CDCl3): d=7.38 (t, J=7.6 Hz, 1H), 7.27 (d, J=7.6 Hz, 1H),
7.25–7.20 (m, 2H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.5–145.3 (m), 143.1–142.8 (m), 141.7–141.4
(m), 139.2–138.9 (m), 138.5, 136.8–136.4 (m), 130.7, 130.1,
128.6, 127.2, 126.2, 116.3–115.9 (m), 21.4.
CDCl3): d=7.63 (d, J=8.2 Hz, 2H), 7.29 (d, J=8.2 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=145.4–145.2 (m),
142.9–142.7 (m), 141.9–141.8 (m), 139.5–139.0 (m), 136.8–
136.5 (m), 132.1, 131.7 (m), 125.3, 123.8, 115.0–114.7 (m).
2,3,4,5,6-Pentafluoro-4’-nitro-1,1’-biphenyl (3i):[2d] Yield:
4’-(tert-Butyl)-2,3,4,5,6-pentafluoro-1,1’-biphenyl (3d):[11]
1
Yield: 60.1 mg (80%); colorless solid; H NMR (400 MHz,
1
60.0 mg (83%); colorless solid; H NMR (400 MHz, CDCl3):
CDCl3): d=7.51 (d, J=8.0 Hz, 2H), 7.36 (t, J=8.0 Hz, 2H),
1.37 (s, 9H); 13C NMR (100 MHz, CDCl3): d=152.5, 145.5–
145.4 (m), 143.1–142.9 (m), 141.6–141.3 (m), 139.3–138.9
(m), 136.8–136.4 (m), 129.8, 125.7, 123.4, 116.1–115.7 (m),
34.8, 31.2; 19F NMR (377 MHz, CDCl3): d=À143.4 (dd, J=
22.1, 8.0 Hz, 2F), À156.2 (t, J=22.1 Hz, 1F), À162.5 (td, J=
22.1, 8.0 Hz, 2F); anal calcd. for C16H13F5: C 64.00, H 4.36;
found: C 64.05, H 4.38.
d=8.37 (d, J=8.4 Hz, 2H), 6.65 (d, J=8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3): d=148.3, 145.4–145.2 (m),
142.9–142.5 (m), 140.2–139.9 (m), 139.4–139.1 (m), 136.9–
136.6 (m), 132.9, 131.3, 123.9, 114.0–113.6 (m).
2-(Perfluorophenyl)naphthalene (3j):[2d] Yield: 56.6 mg
(77%); colorless solid; 1H NMR (400 MHz, CDCl3): d=
2,3,4,5,6-Pentafluoro-4’-methoxy-1,1’-biphenyl
(3e):[2d]
1
Yield: 48.7 mg (71%); colorless solid; H NMR (400 MHz,
7.96–7.89 (m, 4H), 7.57–7.48 (m, 3H); 13C NMR (100 MHz,
CDCl3): d=145.6–145.5 (m), 143.1–143.0 (m), 141.7 (m),
139.3–139.0 (m), 136.6 (m), 133.7, 133.0, 130.1, 128.4, 128.3,
127.8, 127.2, 127.0, 126.7, 123.7, 116.0–115.8 (m).
CDCl3): d=7.36 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H),
3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): d=160.3, 145.5–
145.3 (m), 143.0–142.9 (m), 141.4–141.1 (m), 139.3–138.6
(m), 136.8–136.4 (m), 131.4, 118.4, 115.9–115.5 (m), 114.2,
55.3.
2,3,5,6-Tetrafluoro-4-methyl-1,1’-biphenyl (3l):[3d] Yield:
1
51.0 mg (85%); colorless solid; H NMR (400 MHz, CDCl3):
2,3,4,4’,5,6-Hexafluoro-1,1’-biphenyl
(3f):[2d]
Yield:
1
59.0 mg (90%); colorless solid; H NMR (400 MHz, CDCl3):
d=7.50–7.41 (m, 5H), 2.31 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=146.6–146.4 (m), 144.9–144.7 (m), 144.2–144.0
(m), 142.5–142.2 (m), 130.2, 128.9, 128.5, 127.8, 118.0, 115.1,
7.5.
d=7.43–7.40 (m, 2H), 7.19 (d, J=8.6 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=163.2 (d, J=248.4 Hz), 145.4–145.3
(m), 143.0–142.9 (m), 141.9–141.7 (m), 139.3–138.9 (m),
136.8–136.5 (m), 132.1–132.0 (m), 122.3, 116.0 (d, J=
21.8 Hz), 115.2–114.8 (m).
2,3,5,6-Tetrafluoro-4,4’-dimethyl-1,1’-biphenyl
(3m):[4a]
1
Yield: 50.8 mg (80%); colorless solid; H NMR (400 MHz,
CDCl3): d=7.34 (d, J=7.8 Hz, 2H), 7.31 (d, J=7.8 Hz, 2H),
(s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
2.41ACHTNUGRTNEUNG
4’-Chloro-2,3,4,5,6-pentafluoro-1,1’-biphenyl
(3g):[3d]
Yield: 57.1 mg (82%); colorless solid; H NMR (400 MHz,
1
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Desulfitative Direct C H Arylation of Electron-Deficient Polyfluoroarenes
146.6–146.4 (m), 144.9–144.7 (m), 144.2–144.0 (m), 142.5–
142.2 (m), 138.9, 130.0, 129.3, 124.7, 117.9, 114.7, 21.3, 7.5.
2,3,5,6-Tetrafluoro-4-methoxy-1,1’-biphenyl (3n):[3d] Yield:
1
53.2 mg (83%); colorless solid; H NMR (400 MHz, CDCl3):
7.33 (d, J=8.0 Hz, 2H), 2.44 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.8–145.3 (m), 143.2–142.8 (m), 140.3, 129.8,
129.6, 125.1–124.8 (m), 123.1, 122.3, 119.5, 108.4–108.0 (m),
21.4.
2,3,5,6-Tetrafluoro-4-phenylpyridine
(3s):[3d]
Yield:
d=7.49–7.45 (m, 5H), 4.11 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.6–145.4 (m), 143.2–142.9 (m), 142.5–142.3
(m), 140.1–139.8 (m), 137.6–137.3 (m), 130.2, 128.8, 128.6,
127.3, 114.4–114.0 (m), 62.1 (t, J=3.7 Hz).
1
25.6 mg (45%); colorless solid; H NMR (400 MHz, CDCl3):
2,3,5,6-Tetrafluoro-4-methoxy-4’-methyl-1,1’-biphenyl
(3o):[4a] Yield: 54.7 mg (81%); colorless solid; 1H NMR
d=7.54 (s, 5H); 13C NMR (100 MHz, CDCl3): d=145.4–
145.0 (m), 143.0–142.6 (m), 140.7–140.3 (m), 138.1–137.8
(m), 133.6–133.3 (m), 130.5, 129.7, 128.9, 125.9.
2,3,5,6-Tetrafluoro-1,1’-biphenyl (3t):[3d] Yield: 45.2 mg
(80%); colorless solid; 1H NMR (400 MHz, CDCl3): d=
(400 MHz, CDCl3): d=7.32 (d, J=7.8 Hz, 2H), 7.28 (t, J=
7.8 Hz, 2H), 4.11 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.6–145.4 (m), 143.2–142.9 (m), 142.5–142.3
(m), 140.1–139.8 (m), 138.9, 137.3–137.1 (m), 130.0, 129.3,
124.2, 114.4–114.1 (m), 62.2 (t, J=3.7 Hz), 21.3; 19F NMR
(377 MHz, CDCl3): d=À145.26 (dd, J=22.0, 8.7 Hz, 2F),
À158.4 (dd, J=22.0, 8.7 Hz, 2F); anal calcd. for C14H10F4O:
C 62.23, H 3.73; found: C 62.30, H 3.77.
7.49–7.47 (m, 5H), 7.10–7.02 (m, 1H); 13C NMR (100 MHz,
CDCl3): d=147.6–147.3 (m), 145.1–144.9 (m), 142.6–142.4
(m), 130.1, 129.2, 128.6, 127.5, 121.7–121.3 (m), 105.0–104.6
(m).
4’-Chloro-2,3,5,6-tetrafluoro-4-methoxy-1,1’-biphenyl
(3p):[6a] Yield: 54.5 mg (75%); colorless solid; 1H NMR
2,3,5,6-Tetrafluoro-4’-methyl-1,1’-biphenyl (3u):[4a] Yield:
1
45.4 mg (74%); colorless solid; H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3): d=7.46 (d, J=8.0 Hz, 2H), 7.37 (d, J=
8.0 Hz, 2H), 4.13 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
145.6–145.3 (m), 143.1–142.9 (m), 142.5–142.3 (m), 140.0–
139.8 (m), 137.9–137.6 (m), 135.1, 131.5, 128.9, 125.7, 113.1–
112.8 (m), 62.2 (t, J=3.7 Hz); 19F NMR (377 MHz, CDCl3):
d=À145.1 (dd, J=21.2, 8.9 Hz, 2F), À157.9 (dd, J=21.2,
8.9 Hz, 2F); anal calcd. for C13H7ClF4O: C 53.72, H 2.43;
found: C 53.75, H 2.44.
d=7.35 (d, J=7.6 Hz, 2H), 7.30 (d, J=7.6 Hz, 2H), 7.08–
6.99 (m, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=147.6–147.3 (m), 145.1–144.9 (m), 142.6–142.4 (m), 139.3,
129.9, 129.3, 124.4, 121.7–121.3 (m), 104.7–104.3 (m), 21.3.
2,3,4’,5,6-Pentafluoro-1,1’-biphenyl (3v):[12] Yield: 46.4 mg
(76%); colorless solid; 1H NMR (400 MHz, CDCl3): d=
2,3,5,6-Tetrafluoro-4-(trifluoromethyl)-1,1’-biphenyl
(3q):[6a] Yield: 61.8 mg (84%); colorless solid; 1H NMR
7.47–7.43 (m, 2H), 7.19 (t, J=8.2 Hz, 2H), 7.12–7.03 (m,
1H); 13C NMR (100 MHz, CDCl3): d=163.1 (d, J=
248.2 Hz), 147.6–147.3 (m), 145.2–144.9 (m), 142.6–142.4
(m), 132.1–132.0 (m), 123.3, 120.5, 115.8 (d, J=21.7 Hz),
105.0.
(400 MHz, CDCl3): d=7.53–7.25 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=145.8–145.3 (m), 143.2–142.8 (m),
130.0–129.9 (m), 128.8, 126.1, 125.1–124.7 (m), 122.3, 119.5,
108.7–108.4 (m), 29.7.
2,3,5,6-Tetrafluoro-4’-methyl-4-(trifluoromethyl)-1,1’-bi-
phenyl (3r):[3b] Yield: 57.8 mg (75%); colorless solid;
1H NMR (400 MHz, CDCl3): d=7.37 (d, J=8.0 Hz, 2H),
2,4,6-Trifluoro-4’-methyl-1,1’-biphenyl
26.1 mg (47%); colorless solid; H NMR (400 MHz, CDCl3):
(3w):[4a]
Yield:
1
d=7.31 (d, J=8.0 Hz, 2H), 7.27 (d, J=8.0 Hz, 2H), 6.74 (t,
Adv. Synth. Catal. 2014, 356, 429 – 436
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FULL PAPERS
Tao Miao and Lei Wang
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This work was financially supported by the National Science
Foundation of China (Nos. 21372095, 21172092).
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436
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Adv. Synth. Catal. 2014, 356, 429 – 436