Nickel-catalyzed ortho-selective hydrodefluorination of N-containing heterocycle-polyfluoroarenes

Article abstract of DOI:10.1002/cjoc.201300327

An effective and facile method for preparation of partially fluorinated aromatics via Nickel catalyzed, chelation-assisted ortho selective hydrodefluorination of polyfluoroarnes with triethylsilane has been developed, in which N-containing heterocycles were used as directing groups. The advantage of this protocol is its simple catalytic system with use of inexpensive and readily available NiCl₂·6H₂O as a catalyst. An effective and facile method for preparation of partially fluorinated aromatics via Nickel catalyzed, chelation-assisted ortho selective hydrodefluorination of polyfluoroarnes with triethylsilane has been developed, in which N-containing heterocycles were used as directing groups. Copyright

Full text of DOI:10.1002/cjoc.201300327

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DOI: 10.1002/cjoc.201300327
Nickel-Catalyzed ortho-Selective Hydrodefluorination of
N-Containing Heterocycle-Polyfluoroarenes
Yi He,a,c Zhao Chen,c Chun-Yang He,b and Xingang Zhang*,b
a State Key Lab of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University,
8 Xindu Avenue, Chengdu, Sichuan 610500, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
c School of Chemistry and Chemical Engineering, Southwest Petroleum University, 8 Xindu Avenue,
Chengdu, Sichuan 610500, China
An effective and facile method for preparation of partially fluorinated aromatics via Nickel catalyzed, chela-
tion-assisted ortho selective hydrodefluorination of polyfluoroarnes with triethylsilane has been developed, in
which N-containing heterocycles were used as directing groups. The advantage of this protocol is its simple cata-
lytic system with use of inexpensive and readily available NiCl2•6H2O as a catalyst.
Keywords catalytic C－F activation, hydrodefluorination, nickel, polyfluoroarenes, triethylsilane
Introduction
Very recently, we developed an efficient method for
ortho selective hydrodefluorination of polyfluoroarenes,
in which Pd was used as a catalyst and N-containing
heterocycles were employed as directing groups
(Scheme 1a).[8]
However, from the viewpoint of practicality and cost
effectiveness, the use of less expensive and abundant
metal catalysts, such as nickel, to execute such C－F
bond activation would be promising.[9] To continue our
research, herein, we describe a nickel-catalyzed chela-
tion assisted hydrodefluorination of N-heterocycles sub-
stituted polyfluoroarenes with triethylsilane (Scheme
1b). This protocol provides an effective access to par-
tially fluorinated aromatics that are important in photo-
electronic devices (Figure 1).[10]
Partially fluorinated aromatics are an important class
of fluorinated compounds owning to the presence of
such moieties in a wide range of biologically active
compounds and functional materials of importance in
various application fields.[1] Hence, it is of great interest
to access such fluorinated compounds. Among the
known methods of preparation of partially fluorinated
aromatics,[2,3] the selective C－F activation and func-
tionalization of polyfluoroarenes catalyzed by transi-
tion-metal represents one of the most attractive ap-
proach,[4] as the polyfluoroarenes are more readily
available and cheaper than their mixed halo or or-
ganometal counterparts. In particular, the catalytic hy-
drodeflurorination (HDF) of polyfluoroarenes is the
simplest approach to obtain partially fluoroarenes that
are difficult to obtain otherwise.[5] However, the selec-
tive transition-metal-catalyzed C－F activation remains
a challenge due to the strong bond dissociation energies.
Although many efforts have been made in this area in
the past few years, most of the developed methods for
selective transition-metal-catalyzed HDF of polyfluo-
roarenes mainly focus on the mechanistic understanding
of the HDF cycle.[6] Furthermore, in most of the cases,
only the C－F bonds in the para-position to the sub-
stituent undergo reduction.[7] Therefore, to overcome
these limitations for widespread applications, it is highly
desirable to develop new catalytic system and strategy.
Experimental
General procedure for Ni-catalyzed ortho-selective
hydrodefluorination of N-containing heterocycle-
fluoroarenes with triethylsilane.
To a septum capped 25 mL of sealed tube were
added NiCl2•6H2O (5 mg, 5 mol%), Phen (4 mg, 5
mol%), Zn dust (2.6 mg, 10 mol%), and N-containing
heterocycle-polyfluoroarene 1 (0.4 mmol), followed by
DMF (2.0 mL) with stirring. Triethylsilane (96 μL, 0.6
mmol, 1.5 equiv.) was then added subsequently. The
sealed tube was screw capped and heated to 100 ℃ (oil
bath). After stirring for 8 h, the reaction mixture was
*
E-mail: xgzhang@mail.sioc.ac.cn; Tel.: 0086-21-54925333; Fax: 0086-21-64166128
Received April 19, 2013; accepted June 20, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300327 or from the author.
Chin. J. Chem. 2013, 31, 873—877
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He et al.
COMMUNICATION
Scheme 1 Transition-metal-catalyzed ortho-selective hydrodefluorination of N-heterocycles substituted polyfluoroarenes with triethyl-
silane
Previous work
[PdCl(C3H5)]2 (3.75 mol%)
(a)
dppe (7.5 mol%)
N
N
Et3SiH
+
Fn
Fn
Na2CO3 (2.0 equiv.)
DMF, 120 o
H
2
F
C
1
3
This work
(b)
.
6H2O (5 mol%)
NiCl2
Zn (10 mol%)
N
N
Et3SiH
+
Fn
Fn
Phen (5 mol%)
DMF, 100 o
H
2
F
C
1
3
PF6
F
F3C
F
F
N
N
Ir
Me
Me
F
O
O
N
N
F
F
F
Ir
Fn
F
N
F
F
H
N
N
F
F3C
F
Emitting material,ref 10a, b
Photocatalyst, ref 10c, d
Figure 1 N-Containing heterocyle-fluoroaromatics in photoelectronic materials.
cooled to room temperature, and diluted with ethyl ace-
tate, washed with brine, dried over Na2SO4, filtered and
concentrated. The residue was purified with silica gel
chromatography to provide pure product.
soluble Ni(0) complexes by chelation and increase the
electron density at the nickel center was examined,
providing 3a in 62% yield (determined by 19F NMR)
with trace amount of 4a observed (Table 1, Entry 3).
Prolonging the reaction time to 8 h benefited the
reaction efficiency with 60% isolated yield obtained
(Table 1, Entry 4). Encouraged by these results, a series
of reaction parameters, such as ligands, Ni catalysts, and
the loading amount of Zn dust were investigated (Table
1, Entries 5 － 15). It turned out that Phen is the
optimized one, other ligands, such as bipy and dppe,
were less effective (Table 1, Entries 5, 6). Among the
tested Ni catalysts, NiCl2 provided desired product 3a in
comparable yield (Table 1, Entry 8). Ni(dppp)Cl2
showed the best catalytic effect, but 27% of
dihydrodefluorinated 4a was formed (Table 1, Entry 12).
The loading amount of Zn dust also influenced the
reaction efficiency. Decreasing Zn dust from 10 mol%
to 5 mol% led to lower yield (Table 1, Entry 14).
Similar result was also observed by increasing amount
of Zn dust to 20 mol% due to formation of 21% yield of
dihydrodefluorinated product 4a (Table 1, Entry 15).
Additionally, decreasing the reaction temperature to 90
℃ led to diminished yield as well (Table 1, Entry 16).
The absence of Ni-catalyst failed to give any desired
product (Table 1, Entries 18－20), thus demonstrating
Results and Discussion
In view of the importance of 2-(2,3,4,5-tetrafluoro-
phenyl)pyridine 3a in the light-emitting devices, we
began our studies by choosing 2-(perfluorophenyl)pyri-
dine 1a as the model substrate that can be easily
prepared by the cross-coupling of pentafluoroarene with
2-halopyridine.[2] Initially, a cheap and readily available
NiCl2•6H2O was used as a precatalyst. However, only
9% of hydrodefluorinated 3a was observed when the
reaction was carried out with 1a (1.0 equiv.), Et3SiH
(1.5 equiv.), NiCl2•6H2O (5 mol%) in DMF at 100 ℃
for 6 h (Table 1, Entry 1). Considering that an active
Ni(0) catalyst may be involved in the catalytic cycle,
which undergoes oxidation of C－F bond ortho to the
pyridyl group, Zn dust (10 mol%) was added to reaction
(Table 1, Entry 2). To our delight, the yield of 1a was
improved to 23% yield (determined by 19F NMR) albeit
formation of 7% yield of dihydrodefluorinated product
4a. To further improve the reaction efficiency, diamine
ligand 1,10-phenanthroline (Phen) that can stabilize the
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Chin. J. Chem. 2013, 31, 873—877

Nickel-Catalyzed ortho-Selective Hydrodefluorination of N-Containing Heterocycle-Polyfluoroarenes
that Ni species is involved in the catalytic cycle.
fluorine atoms afforded higher yields, such as difluoro-
arenes 1i and 1j (Table 2, 3i and 3j). In particular, for 1j
a good yield (81%) was obtained (Table 2, 3j). This is
in sharp contrast to our previous results using Pd-
catalyst, in which difluoroarenes 1i and 1j are ‘inert’
substrates,[8] thus featuring the advantages of Ni-catalyst.
In addition, using sequential C－F activation strategy,
the dihydrodefluorinated 3f can also be obtained in
moderate yield from 3c (Table 2, 3f), providing a facile
access to partially fluorinated aromatics that are difficult
to prepare otherwise. However, for 3c and 3d, Ph3SiH
was used due to formation of a mixture of mono- and
dihydrodefluorinated products when Et3SiH was
employed (Table 2, 3c and 3d).
To demonstrate the pivotal role of 2-pyridyl group in
this Ni-catalyzed ortho selective hydrodefluorination,
the investigation of 2,3,4,5,6-pentafluoro-4'-methyl-
1,1'-biphenyl 5 under the optimized reaction conditions
was performed (Scheme 2a). However, no desired hy-
drodefluorinated product 6 was observed. Furthermore,
the use of 3-(2-fluorophenyl)pyridine 7 failed to give
compound 8 either (Scheme 2b). Thus, these findings
demonstrated that the 2-pyridyl group indeed function-
alizes as a directing group to chelate Ni species and
facilitates the catalytic cycle.
Given the low cost and commercial availability of
NiCl2•6H2O, a variety of N-containing heterocycle-
fluoroarenes 1[11] were examined under the reaction
conditions as shown in Table 1 entry 4. Substrates
bearing functionalized pyridyl or quinolinyl groups
underwent the reaction smoothly, providing their
corresponding ortho hydrodefluorinated aromatics in
moderate to good yields with high regioselectivity
(Table 2). Interestingly, fluoroarenes bearing less
Conclusions
In conclusion, we have developed a Ni-catalyzed
ortho-selective hydrodefluorination of N-containing
heterocycle-fluoroarenes with silane, which provides an
effective and facile access to partially fluorinated
Table 1 Optimization of Ni-catalyzed ortho-selective C－F activation of 1a with triethylsilanea
F
F
[Ni] (x mol%)
Zn (y mol%)
F
H
F
F
F
F
F
F
N
N
N
Et3SiH
+
+
Ligand (z mol%)
DMF, 100 oC, 6 - 8 h
2
F
H
H
F
3a
F
1a
4a
Entry
1c
2c
[Ni] (x)
Zn (y)
Ligand (z)
3a, yieldb/%
4a, yieldb/%
－
－
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
Ni(OAc)2•4H2O (5)
NiCl2 (5)
9
23
ND
7
10
10
10
10
10
10
10
10
10
10
10
10
5
－
3c
Phen (5)
Phen (5)
Bipy (5)
dppe (5)
Phen (5)
Phen (5)
Phen (5)
Phen (5)
Phen (5)
Phen (5)
Phen (2.5)
Phen (2.5)
Phen (2.5)
Phen (5)
Phen (2.5)
Phen (2.5)
－
62
－
6
4
75 (60)
48
5
－
－
－
7
6
61
7
65
8
71
9
Ni(acac)2 (5)
Ni(dppf)Cl2 (5)
Ni(PPh3)2Cl2 (5)
Ni(dppp)Cl2 (5)
NiCl2•6H2O (2.5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
NiCl2•6H2O (5)
－
trace
68
－
－
9
10
11
12
13
14
15
16d
17
18
19
20
73
73
27
－
－
21
－
－
－
－
－
38
46
20
10
－
－
10
10
50
50
7
NR
NR
NR
－
－
Phen (2.5)
a Unless otherwise noted, the reaction was carried out by using 1a (0.4 mmol, 1 equiv.), Et3SiH 2 (1.5 equiv.) in DMF (2 mL) for 8 h. ND,
not determined. NR, no reaction. b NMR yield determined by 19F NMR using fluorobenzene as internal standard and number in parenthe-
sis is isolated yield. c Reaction conducted for 6 h. d Reaction conducted at 90 ℃.
Chin. J. Chem. 2013, 31, 873—877
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He et al.
COMMUNICATION
Scheme 2 Reaction of 2,3,4,5,6-pentafluoro-4'-methyl-1,1'-biphenyl 5 or 3-(2-fluorophenyl)pyridine 7 with triethylsilane in the
presence of nickel
F
.
F
F
6H2O (5 mol%)
NiCl2
F
F
F
F
Zn (10 mol%)
(a)
Et3SiH
+
Phen (5 mol%)
DMF, 100 oC, 8 h
H
2
F
F
5
6, No reaction
.
NiCl2
6H2O (5 mol%)
N
(b)
N
Zn (10 mol%)
Et3SiH
+
Phen (5 mol%)
DMF, 100 oC, 8 h
H
2
F
8, No reaction
7
Table 2 Ni-catalyzed ortho selective hydrodefluorination of N-containing heterocycle-fluoroarenes 1a
.
NiCl2
6H2O (5 mol%)
Zn (10 mol%)
N
N
+
Et3SiH
Fn
Fn
Phen (5 mol%)
DMF, 100 oC, 8 h
H
2
F
n = 2 - 4
3
1
F
F
F
F
F
F
F
F
F
F
F
F
N
N
F
F
N
N
F
N
N
H
H
CF3
F
H
CF3
H
H
OMe
F
3c, 52%b
3d, 55%b
3a, 60%
3b, 63%
3e, 67%
F
F
H
F
F
N
N
N
N
H
CF3
H
H
F
H
F
F
F
F
3f, 65%
3g, 62%
3h, 62%
3i, 75%
3j, 81%
a Unless otherwise noted, the reaction was carried out by using 1 (0.4 mmol, 1 equiv.), Et3SiH 2 (1.5 equiv.) in DMF (2 mL) for 8 h. All
reported reaction yields are isolated yields. b 1.5 equiv. of Ph3SiH was used.
aromatics that are difficult to prepare otherwise. The
advantage of this reaction is its simple catalytic system
with use of inexpensive and readily available
NiCl2•6H2O as a catalyst. Further studies to expand the
substrates scope and uncover the reaction mechanism
are currently in progress.
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search Program of China (973 Program) (No.
2012CB821600), the Science and Technology Key Re-
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voir Geology and Exploitation (No. PLN0806), and
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 873—877

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(Lu, Y.)
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