Nickel-catalyzed cross-coupling of aryl fluorides and organozinc reagents

Article abstract of DOI:10.1021/jo500619f

Ni(PCy₃)₂Cl₂ was demonstrated to effectively catalyze cross-coupling of aryl fluorides and organozinc reagents. Both electron-poor and -rich aryl fluorides can react effectively with nucleophiles including aryl-, methyl-, and benzylzinc chlorides. A wide range of substituents and functional groups are tolerated. In the presence of a directing group, PhC(O), the reaction is selective for cleavage of the C-F bond ortho to the carbonyl substituent in a difluoroarene.

Full text of DOI:10.1021/jo500619f

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pubs.acs.org/joc
Nickel-Catalyzed Cross-Coupling of Aryl Fluorides and Organozinc
Reagents
Feng Zhu and Zhong-Xia Wang*
CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry, University of Science and Technology of China, Hefei,
Anhui 230026, People’s Republic of China
S
* Supporting Information
ABSTRACT: Ni(PCy3)2Cl2 was demonstrated to effectively catalyze cross-
coupling of aryl fluorides and organozinc reagents. Both electron-poor and
-rich aryl fluorides can react effectively with nucleophiles including aryl-,
methyl-, and benzylzinc chlorides. A wide range of substituents and functional
groups are tolerated. In the presence of a directing group, PhC(O), the
reaction is selective for cleavage of the C−F bond ortho to the carbonyl substituent in a difluoroarene.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Transition-metal-catalyzed activation and transformation of C−
F bonds have received considerable attention over the years.1
On one hand, fluorine forms the strongest known single bond
to carbon. The conversion of organic fluorides is important for
the fundamental understanding of the reactivity of very stable
chemical bonds. On the other hand, activation of the carbon−
fluorine bond is of importance for selective transformation of
polyfluorinated compounds to partially fluorinated compounds
which offer potential use in drug discovery and materials
science.1,2 The catalytic transformation of C−F bonds such as
hydrodefluorination,1e C−C coupling,1,3−7 C−N coupling,8 and
C−S coupling9 of fluoride substrates has been reported. The
reported C−C cross coupling includes Kumada coupling,3
Negishi coupling,1d,4 Suzuki coupling,5 Stille coupling,6 and
Sonogashira coupling.7 Among them, Kumada coupling of aryl
fluorides appeared at very early stages of cross-coupling
investigations, and subsequent studies also occurred more
often than studies of other types of cross-coupling reactions.
Negishi cross-coupling of aryl fluorides appeared relatively late,
and only electron-poor fluoride substrates were successfully
coupled. In addition, several Negishi cross-coupling reactions
containing selective C−F bond activation of polyfluoroarenes
for synthesis of partially fluorinated aromatics have been
performed.1d,4c−i For example, Love et al. carried out platinum-
catalyzed cross-coupling of polyfluoroarylimines with dimethyl-
zinc in which the C−F bonds ortho to an imine substituent are
selectively cleaved.4d−f Nakamura et al. performed nickel-
catalyzed monosubstitution of polyfluoroarenes with organo-
zinc reagents using alkoxydiphosphine ligand.4c Ogoshi et al.
reported similar work using palladium(0)/PCy3 catalyst.4g In
our exploration of C−F bond activation we found that
commercially available Ni(PCy3)2Cl2 is an effective catalyst
that can catalyze cross-coupling of activated and deactivated
aryl fluorides with arylzinc reagents or β-hydrogen-free
alkylzinc reagents and selective activation of C−F bonds in
(2,5-difluorophenyl)(phenyl)methanone. Herein we report the
results.
We first screened the catalysts, solvents, and other reaction
conditions using a model reaction between p-FC6H4OMe and
2.5 equiv of p-MeC6H4ZnCl prepared from p-MeC6H4Li and
ZnCl2 (Table 1). It has been reported that a 1:1 mixture of
THF and NMP is a suitable solvent for cross-coupling of
arylzinc reagents and aryl chlorides. We also employed 1:1
THF−NMP as the solvent to screen catalysts. Pd(PPh3)2Cl2
and Pd(OAc)2/dppp cannot give the desired products.
Pd(OAc)2/PCy3 led to the corresponding cross-coupling
product in low yield (Table 1, entries 1−3). Nickel complexes
such as Ni(dppe)Cl2 and Ni(dppf)Cl2 gave better results
compared with those mentioned above (Table 1, entries 4 and
5). This led us to explore nickel catalyts systematically.
Ni(acac)2 alone or a combination of Ni(acac)2 and dppp or
IPr·HCl was found to lead to the coupling product in 51%−
72% yields (Table 1, entries 6−8). Ni(PCy3)2Cl2 displayed a
better catalytic activity, resulting in 74% yield of coupling
product. By contrast, Ni(PPh3)2Cl2 was inactive, and Ni-
(PMe3)2Cl2 led to relatively low product yield (Table 1, entries
9−11). From the screened results it seems that an electron-rich
ligand such as PCy3 and IPr is better for the activation of C−F
bonds. This may be because an electron-rich metal center is
beneficial to the oxidative addition of the aryl fluoride. When
1.5 equiv of p-MeC6H4ZnCl were employed, the product yield
decreased to 68% (Table 1, entry 12). However, if an additional
1 equiv of p-MeC6H4ZnCl was added after the reaction of p-
FC6H4OMe and 1.5 equiv of p-MeC6H4ZnCl for 10 h, a
marked increase of the yield was observed (Table 1, entry 13).
Further improvement of the yield was carried out by changing
the reaction temperature from 120 to 100 °C (both are bath
temperature) (Table 1, entry 14). It was noted that decreasing
the catalyst loading led to yield decrease (Table 1, entry 15). In
the reaction, the presence of lithium ion seems to be important.
If the zinc reagent used in the reaction was prepared from p-
Received: March 17, 2014
Published: April 23, 2014
© 2014 American Chemical Society
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conditions (Table 2). Reaction of both 4-fluoro-1,1′-biphenyl
and 1-fluoronaphthalene with p-MeC6H4ZnCl gave excellent
Table 1. Screening of Catalysts and Solvents in the Reaction
of p-MeOC6H4F with p-MeC6H4ZnCl
a
Table 2. Nickel-Catalyzed Coupling of Aryl or Heteroaryl
a
Fluorides with p-MeC6H4ZnCl
yield
entry
catalyst
Pd(PPh3)2Cl2
solvent
(%)
1
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
2
Pd(OAc)2 + 20 mol % dppp
Pd(OAc)2 + 20 mol % PCy3
Ni(dppe)Cl2
3
18
30
36
51
66
72
74
trace
44
68
90
92
80
44
56
92
70
26
4
5
Ni(dppf)Cl2
6
Ni(acac)2
7
Ni(acac)2 + 10 mol % dppp
8
Ni(acac)2 + 20 mol % IPr·HCl THF−NMP (1:1)
9
Ni(PCy3)2Cl2
Ni(PPh3)2Cl2
Ni(PMe3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:1)
THF−NMP (1:2)
dioxane
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
b
c
c
c
,
,
d
d
,
e
f
g
c
c
,
d
d
,
,
,
f,g
toluene
THF (reflux)
trace
trace
39
THF−toluene (1:1)
THF−dioxane (1:1)
a
Unless otherwise specified, the reactions were carried out on a 0.5
mmol scale according to the conditions indicated by the above
equation; p-MeC6H4ZnCl was prepared from p-MeC6H4Li and ZnCl2;
b
2.5 equiv of p-MeC6H4ZnCl was employed. 1.5 equiv of p-
c
MeC6H4ZnCl was employed. 2.5 equiv of p-MeC6H4ZnCl was
added in two portions. 1.5 equiv of p-MeC6H4ZnCl was added at first,
after stirring for 10 h an additional 1 equiv of p-MeC6H4ZnCl was
d
e
added. The reaction was carried out at 100 °C. 5 mol % of
f
Ni(PCy3)2Cl2 was employed. The p-MeC6H4ZnCl was prepared from
p-MeC6H4MgBr and ZnCl2. 2 equiv of LiCl was added.
g
MeC6H4MgBr and ZnCl2, the product yield fell remarkably
whether or not the zinc reagent was add in one or two portions
(Table 1, entries 16 and 17). However, 2 equiv of LiCl additive
evidently improved the reaction result (Table 1, entry 18). A
similar phenomenon was observed by other groups.4g,10a The
low reactivity of the zinc reagent prepared from a Grignard
reagent and ZnCl2 might be due to aggregation of the arylzinc
reagent with the coproduct MgCl2. The role of LiCl additive
might include (i) to break the aggregation mentioned above
and (ii) to enhance the elimination ability of fluorine through
acting as a Lewis acid and forming a strong Li−F bond.4a,g,10 In
addition, Ni(PCy3)2Cl2 was reported to be an effective catalyst
for aryl−O bond activation.11 However, no aryl-OMe activation
product was obtained under the screening conditions. We also
examined the solvent effect by employing different solvents in
the reaction, including a 1:2 mixture of THF and NMP,
dioxane, toluene, and THF and an equivalent mixture of THF
and toluene or dioxane. However, the results showed that each
of these solvents was less effective than a 1:1 mixture of THF
and NMP (Table 1, entries 19−24).
a
The reactions were carried out on a 0.5 mmol scale according to the
conditions indicated by the above equation unless otherwise specified;
p-MeC6H4ZnCl was prepared from p-MeC6H4Li and ZnCl2. 1.5 equiv
of p-MeC6H4ZnCl was added into the reaction system and reacted for
10 h; an additional 1 equiv of p-MeC6H4ZnCl was added. Reaction
was carried out at 120 °C. 3.0 equiv of p-MeC6H4ZnCl was added in
one portion, and reaction was run at 80 °C. 2.5 equiv of p-
MeC6H4ZnCl was added, and the reaction was run for 12 h. The
reaction was carried out on a 5 mmol scale.
b
c
d
e
yields (Table 2, entries 1 and 2). Deactivated aryl fluorides such
as p-FC6H4OMe and m-FC6H4OMe also gave excellent results
(Table 1, entries 13 and 14, and Table 2, entry 3). However, p-
FC6H4NMe2 resulted in relatively low yield (Table 2, entry 4).
This is ascribed to strongly deactivated action of the amino
group. A series of electron-withdrawing group substituted
fluorobenzenes showed good reactivity (Table 2, entries 5−10),
each giving high product yield. The high reactivity of the
electron-poor aryl fluorides is because electron-withdrawing
Next, the scope of aryl fluorides was tested using p-
MeC6H4ZnCl as the nucleophilic reagent under the optimized
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a
Table 3. Nickel-Catalyzed Coupling of Aryl Fluorides with Arylzinc/Alkylzinc Reagents
a
Unless otherwise specified, the reactions were carried out on a 0.5 mmol scale according to the conditions indicated by the above equation; R1ZnCl
was prepared from RLi and ZnCl2 and was added into the reaction system in two portions; 1.5 equiv was added at first and an additional 1 equiv was
b
c
d
added after 10 h. 2.5 equiv of ArZnCl was added in one portion. Reaction was run at 80 °C. 3 equiv of CH3ZnCl was added in one portion.
substituents on the aromatic rings are beneficial to the oxidative
addition. Ortho-position substituted fluorobenzenes gave
comparable results to their para-position partners. Functional
groups including C(O)Ph, COOR, CONEt2, and CH
NCHPh2 can be tolerated. However, the CHNCHPh2
group was converted into a CHO group due to hydrolysis
during workup. 2- and 3-fluoropyridines exhibited excellent
reactivity when treated with p-MeC6H4ZnCl in the presence of
Ni(PCy3)2Cl2. The arylzinc reagent (2.5 equiv) was added in
one portion, and the reaction can be completed in 12 h in
almost quantitative yields (Table 2, entries 11 and 12). In
addition, we examined reaction of p-FC6H4OMe with p-
MeC6H4ZnCl on a 5 mmol scale. A yield was obtained similar
to that of the 0.5 mmol scale under the same conditions (Table
2, entry 13).
MeC6H4ZnCl. However, it led to lower yields than p-
MeC6H4ZnCl when reacted with aryl fluorides including 1-
fluoronaphthalene, p-PhC(O)C6H4F, o-MeOC(O)C6H4F, and
o-PhC(O)C6H4F with unestablished reasons (Table 3, entries
1−4). Reaction of p-MeOC6H4ZnCl with p-Et2NC(O)C6H4F
or p-CF3C6H4F gave excellent results (Table 3, entries 5 and
6). o-MeC6H4F exhibited low reactivity upon reaction with p-
MeOC6H4ZnCl (Table 3, entry 7). This might be due to steric
hindrance of he methyl group in o-MeC6H4F. p-
Me2NC6H4ZnCl showed excellent reactivity toward either
electron-rich or electron-poor fluoroarenes (Table 3, entries 8−
11). p-CF3C6H4ZnCl showed relatively weak nucleophilicity. It
did not react with p-MeOC6H4Cl. However, it can couple with
2- or 3-fluoropyridine, forming the desired coupling products in
93% and 76% yields, respectively. Both o-MeC6H4ZnCl and (1-
naphthyl)ZnCl are hindral nucleophiles. Reaction of o-
MeC6H4ZnCl with p-MeOC6H4Cl gave 75% yield of the
Various zinc reagents were also tested for the couplings. p-
MeOC6H4ZnCl is a stronger nucleophilic reagent than p-
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cross-coupling product, while reaction of (1-naphthyl)ZnCl
with p-MeOC6H4Cl afforded the corresponding product in
only 13% yield. However, both zinc reagents resulted in high
product yields when reacted with 2-fluoropyridine (Table 3,
entries 15 and 17). The reactivity of (2-furyl)ZnCl was also
tested. It reacted smoothly with activated fluoroarenes such as
o-PhC(O)C6H4F and 2-fluoropyridine and gave high product
yields, but its reaction with p-CF3C6H4F led to relatively low
yield. No reaction took place between (2-furyl)ZnCl and p-
MeOC6H4Cl. β-Hydrogen-free alkylzinc reagents such as
PhCH2ZnCl and MeZnCl can be used as the nucleophiles in
the cross-coupling reactions (Table 3, entries 21−24). p-
PhC(O)C6H4F, o-PhC(O)C6H4F, and 2-fluoropyridine were
proven to couple with PhCH2ZnCl or MeZnCl effectively,
affording the desired products in excellent yields. Reaction of β-
hydrogen-containing alkylzinc reagents with an aryl fluoride
resulted in a mixture of cross-coupling product and reductive
product of the aryl fluoride. This showed that partial β-
hydrogen elimination occurred during the reaction process.
Recently, Love and co-workers carried out Ni(PEt3)2Cl2-
catalyzed cross-couplings of aryl fluorides with imino directing
group and β-hydrogen-containing alkylzinc reagents.4i In the
reactions, it seems that the PEt3 ligand and the imino group
together provide a proper coordination environment for the
central nickel atom which effectively suppresses β-hydrogen
elimination from the reaction intermediates. The preparative
method of the organozinc reagents and reaction conditions
such as reaction temperature and solvents may also be
responsible for the outcomes in comparison with our reaction
system.
to introduce a suitable directing group onto the fluoride
substrate. Indeed, in the presence of a directing group PhC(O)
in the fluoride substrate partial C−F bond activation can be
carried out by Ni(PCy3)2Cl2 (Table 4). Reaction of (2,5-
Table 4. Selective Substitution of (2,5-
a
Difluorophenyl)(phenyl)methanone
yield (%)
entry
RZnCl
time (h)
2
3
1
2
p-MeC6H4ZnCl (1.5 equiv)
(2-furyl)ZnCl (1.5 equiv)
PhCH2ZnCl (1.5 equiv)
PhCH2ZnCl (2.5 equiv)
CH3ZnCl (2.5 equiv)
12
12
16
16
16
85
79
52
61
91
0
0
0
0
9
b
3
c
4
d
5
a
The reactions were carried out on a 0.5 mmol scale according to the
conditions indicated by the above equation; R1ZnCl was prepared
from R1Li and ZnCl2 and was added into the reaction system in one
b
portion. A mixture of 2 and starting material was obtained, and their
c
ratio was calculated by 1H NMR integrals. Products isolated by
d
preparative TLC. GC yield.
difluorophenyl)(phenyl)methanone with 1.5 equiv of p-
MeC6H4ZnCl under the same catalyst, solvents, and temper-
ature as above for 12 h afforded an o-arylated product (4-fluoro-
4′-methylbiphenyl-2-yl)(phenyl)methanone in 85% yield. No
5-position arylated product or biarylated product was obtained.
A similar ortho-arylated product was obtained when (2-
furyl)ZnCl was employed as the nucleophile (Table 4, entry
2). A small amount of starting material was determined by TLC
in the reactions with either p-MeC6H4ZnCl or (2-furyl)ZnCl.
PhCH2ZnCl showed relatively low reactivity. Reaction of 1.5
equiv of PhCH2ZnCl with (2,5-difluorophenyl)(phenyl)-
methanone under the same conditions for 16 h gave a mixture
of o-benzylated product (52%) and starting material (41%).
Excess PhCH2ZnCl (2.5 equiv) can lead to an increase of the
yield of o-benzylated product (61% yield), but 21% of the
starting material still remained (Table 4, entries 3 and 4).
MeZnCl exhibited higher reactivity than PhCH2ZnCl in the
reaction with (2,5-difluorophenyl)(phenyl)methanone. The
reaction resulted in 91% yield of o-methylated product (5-
fluoro-2-methylphenyl)(phenyl)methanone, accompanied by
9% yield of bimethylated product (2,5-dimethylphenyl)-
(phenyl)methanone (Table 4, entry 5). We also tested other
potential directing groups including COOMe and imine group
in a difluoride system, but both led to mixtures when they
reacted with p-MeC6H4ZnCl under the same conditions as
above.
Di- or trifluorobenzenes were also effectively coupled with
arylzinc reagents under the conditions mentioned above
(Scheme 1). Reaction of 1,4-difluorobenzene with 5.0 equiv
Scheme 1. Nickel-Catalyzed Cross-Coupling of
Multibenzenes with Arylzinc Chlorides
of p-MeC6H4ZnCl afforded 1,4-bis(p-tolyl)benzene in 78%
yield. Treatment of 1,3,5-trifluorobenzene with 7.5 equiv of p-
MeOC6H4ZnCl (4.5 equiv of ArZnCl was added at first and
then an additional 3 equiv of ArZnCl was added after 10 h)
gave 1,3,5-tris(4-methoxyphenyl)benzene in 80% yield. At-
tempts to selectively prepare a monoarylated product using a
smaller amount of arylzinc reagents under the same catalyst and
conditions were unsuccessful. This may result from “ring
walking” in the product/catalyst complex caused by strong
back-donation as indicated by Nakamura et al.4c Two strategies
have been used to achieve selective C−F monofunctionalization
from polyfluoroarenes. One is ligand design and metal ligand
cooperation. The proper ligands can provide the most
appropriate coordination environment for the metal center,
which makes the catalyst complex suppress multisubstitution of
polyfluoroarenes caused by ring walking. The other strategy is
Our previous work showed that the C−CN bond of p-
FC6H4CN can be catalytically cut off and coupled with a
manganese reagent.12 In the present study, we noticed that the
C−CN bond and C−F bond can be sequentially activated and
coupled in one pot, giving an unsymmetrical terphenyl
(Scheme 2). In this reaction, two very inert chemical bonds
were respectively activated. The Ni(PMe3)2Cl2 catalyst and
excess manganese reagent added in the first step did not affect
the following Negishi-type coupling.
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Scheme 2. Sequential Cross-Coupling To Construct
Unsymmetrical Terphenyl
Scheme 3. Proposed Mechanism for the Coupling of Aryl
Fluorides and Organozinc Reagents
A preliminary study of the mechanism for the nickel-
catalyzed reaction of aryl fluorides with organozinc reagents
was also carried out. The reaction of p-FC6H4OMe with p-
MeC6H4ZnCl was first tested in the absence of Ni(PCy3)2Cl2
in a mixed solvent of THF and NMP (1:1) at 120 °C for 20 h.
No cross-coupling product was obtained. Next we tested the
reaction of (2-fluorophenyl)(phenyl)methanone with p-
MeOC6H4ZnCl in the absence of Ni(PCy3)2Cl2 in THF−
NMP (1:1) at 100 °C for 12 h. No cross-coupling product can
be isolated either. These experimental facts ruled out the
possibility of a direct nucleophilic substitution and a
coordination-assisted nucleophilic substitution. 1,1-Diphenyl-
ethylene additive (an equimolar amount with p-FC6H4OMe)
did not affect the reaction of p-FC6H4OMe with p-
MeC6H4ZnCl catalyzed by Ni(PCy3)2Cl2 (10 mol %). It
seems that the reaction did not proceed via a free-radical
process. Further experiment showed that a mixture of
Ni(COD)2 (10 mol %) and PCy3 (20 mol %) effectively
catalyzed the cross-coupling of p-FC6H4OMe with p-
MeC6H4ZnCl, giving the desired product in 76% yield.
Hence, the active catalyst may be a Ni(0) species. Attempts
to isolate the oxidative addition product of Ni(0) and aryl
fluoride via reaction of Ni(COD)2/2PCy3 and (2-
fluorophenyl)(phenyl)methanone failed. Reaction of Ni-
(COD)2/2PCy3 and 1 equiv of (2-fluorophenyl)(phenyl)-
methanone was run at 80 °C for 12 h. The 19F{1H} NMR
spectrum of the reaction mixture showed that about 30% of (2-
fluorophenyl)(phenyl)methanone was transformed to a new
species, supposing oxidative addition product. Most (2-
fluorophenyl)(phenyl)methanone remained. However, after p-
MeC6H4ZnCl (2.5 equiv) was added into the reaction system
and the mixture was stirred at 100 °C for 12 h, the cross-
coupling product was obtained in 94% yield. Hence, arylzinc
reagent may promote the oxidative addition process. Based on
the above experimental facts and the mechanism studies of
transition-metal-catalyzed cross-coupling reactions reported in
the literature,13 a possible mechanism is proposed as shown in
Scheme 3. Thus, a Ni(0) species is first generated by reaction of
Ni(PCy3)2Cl2 with the zinc reagent. The Ni(0) species L2Ni(0)
reacts with ArF results in a oxidative addition product
L2Ni(F)Ar. Reaction of L2Ni(F)Ar with a organozinc reagent,
RZnCl, affords L2Ni(R)Ar which undergoes reductive elemi-
nation to give cross-coupling product and regenerates L2Ni(0).
poor arylzinc reagents including substituted phenylzinc
chlorides, 1-naphthylzinc chloride, and 2-furylzinc chloride
and β-hydrogen free alkylzinc reagents such as benzylzinc
chloride and methylzinc chloride were proven to be suitable
nucleophiles. Pyridyl ring and a range of functional groups
involving NMe2, OMe, CF3, COOEt, C(O)NEt2, PhC(O), and
imino groups were tolerated. We also confirmed that the
PhC(O) group is an effective directing group for the selective
activation of C−F bonds in (2,5-difluorophenyl)(phenyl)-
methanone molecule, with o-arylated or o-alkylated products
being formed.
EXPERIMENTAL SECTION
■
The reactions were performed under nitrogen atmosphere. Toluene
and 1,4-dioxane were distilled under nitrogen over sodium and
degassed prior to use. THF was distilled under nitrogen over sodium/
benzophenone and degassed prior to use. NMP was dried over 4 Å
molecular sieves, fractionally distilled under reduced pressure, and
stored under nitrogen atmosphere. N-(2-Fluorobenzylidene)-1,1-
diphenylmethanamine14 and aryllithium reagents15 were prepared
according to literature methods. Other chemicals and solvents were
purchased from commercial venders and used as received. NMR
spectra were determined on a 300 or 400 MHz NMR spectrometer at
room temperature using CDCl3 as solvent. The chemical shifts of the
1H and 13C NMR spectra were referenced to TMS or internal solvent
resonances. High-resolution mass spectra (HR-MS) were acquired in
the electron impact mode (EI) using a TOF mass analyzer.
General Procedure for Reaction of Aryl Fluorides with
RZnCl. A Schlenk tube was charged with aryl fluoride (0.5 mmol),
Ni(PCy3)2Cl2 (34.6 mg, 0.05 mmol), and NMP (1.5 mL). To the
solution was added a solution of RZnCl (1.5 mL, 0.5 M in THF, 1.5
mmol) at 25 °C with stirring. After the mixture was stirred at 100 °C
(bath temperature) for 10 h, NMP (1 mL) and RZnCl (1 mL, 0.5 M
in THF, 1 mmol) were successively added. The resulting mixture was
stirred at 100 °C (bath temperature) for an additional 10 h. Water (10
mL) and several drops of acetic acid were successively added into the
Schlenk tube. The mixture was extracted with Et2O (3 × 10 mL). The
combined organic phases were dried over Na2SO4, concentrated by
rotary evaporation, and purified by column chromatography on silica
gel.
Spectral Data for the Cross-Coupling Products. 4-Methoxy-
4′-methylbiphenyl.16 Eluent: petroleum ether; yield 92 mg (92%). 1H
NMR: δ 2.36 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 6.94 (d, J = 8.7 Hz,
2H, C6H4), 7.20 (d, J = 8.2 Hz, 2H, C6H4), 7.43 (d, J = 8.1 Hz, 2H,
C6H4), 7.49 (d, J = 8.6 Hz, 2H, C6H4). 13C{1H} NMR: δ 21.2, 55.4,
114.3, 126.7, 128.1, 129.6, 133.9, 136.4, 138.1, 159.1.
CONCLUSION
■
We have demonstrated that the cross-coupling of aryl fluorides
with organozinc reagents can be carried out using Ni-
(PCy3)2Cl2 as the catalyst. Both activated and deactivated aryl
fluorides can be efficiently coupled. Electron-rich and electron-
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dx.doi.org/10.1021/jo500619f | J. Org. Chem. 2014, 79, 4285−4292

The Journal of Organic Chemistry
Featured Article
4-(4-Methylphenyl)biphenyl.5a Eluent: petroleum ether; yield 116
(4′-Methoxybiphenyl-4-yl)(phenyl)methanone.22 Eluent: petrole-
um ether/ethyl acetate = 8:1; yield 84 mg (58%). 1H NMR: δ 3.87 (s,
3H), 7.01 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8 Hz, 2H), 7.58−7.61 (m,
3H), 7.66 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 8.4
Hz, 2H). 13C{1H} NMR: δ 55.5, 114.6, 126.5, 128.4, 128.5, 130.1,
130.9, 132.4, 132.5, 135.7, 138.0, 145.0, 160.0, 196.4.
1
mg (95%). H NMR: δ 2.40 (s, 3H), 7.25 (d, J = 8.1 Hz, 2H), 7.31−
7.37 (m, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.63
(d, J = 7.2 Hz, 2H), 7.65 (s, 4H). 13C{1H} NMR: δ 21.3, 127.0, 127.2,
127.4, 127.6, 128.9, 129.7, 137.3, 138.0, 140.0, 140.2, 140.9.
1-p-Tolylnaphthalene.16 Eluent: petroleum ether; yield 108 mg
(99%). H NMR: δ 2.45 (s, 3H, CH3), 7.29 (d, J = 8.1 Hz, 2H, Ar),
Methyl 4′-Methoxybiphenyl-2-carboxylate.19 Eluent: petroleum
1
1
7.38−7.53 (m, 6H, Ar), 7.83 (d, J = 8.1 Hz, 1H, Ar), 7.90 (t, J = 8.1
Hz, 2H, Ar). 13C{1H} NMR: δ 21.4, 125.5, 125.9, 126.1, 126.3, 127.0,
127.6, 128.4, 129.1, 130.1, 131.9, 134.0, 137.1, 138.0, 140.4.
ether/ethyl acetate = 100:1; yield 85 mg (70%). H NMR: δ 3.65 (s,
3H), 3.81 (s, 3H), 6.92 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H),
7.32−7.37 (m, 2H), 7.45−7.50 (m, 1H), 7.76−7.79 (m, 1H). 13C{1H}
NMR: δ 52.0, 55.3, 113.6, 126.8, 129.5, 129.8, 130.8, 131.0, 131.2,
133.7, 142.1, 159.1, 169.4.
3-Methoxy-4′-methylbiphenyl.17 Eluent: petroleum ether; yield 90
1
mg (90%). H NMR: δ 2.39 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 6.87
(dd, J = 2.4, 8.1 Hz, 1H, C6H4), 7.11 (s, 1H, C6H4), 7.16 (d, J = 7.8
Hz, 1H, C6H4), 7.24 (d, J = 7.8 Hz, 2H, C6H4), 7.33 (t, J = 7.9 Hz, 1H,
C6H4), 7.48 (d, J = 8.1 Hz, 2H, C6H4). 13C{1H} NMR: δ 21.2, 55.4,
112.5, 112.9, 119.6, 127.2, 129.6, 129.8, 137.3, 138.4, 142.9, 160.1.
4′-Methyl-N,N-dimethylbiphenyl-4-amine.16 Eluent: petroleum
(4′-Methoxylbiphenyl-2-yl)(phenyl)methanone.23 Eluent: petrole-
um ether/ethyl acetate = 100:1; yield 104 mg (72%). 1H NMR: δ 3.59
(s, 3H), 6.63 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.16 (t, J =
7.7 Hz, 2H), 7.27−7.46 (m, 5H), 7.55 (d, J = 7.5 Hz, 2H). 13C{1H}
NMR: δ 55.2, 113.9, 126.7, 128.2, 128.7, 129.97, 130.04, 130.2, 130.4,
132.7, 132.9, 137.5, 139.0, 140.8, 159.1, 199.0.
1
ether/ethyl acetate = 100:1; yield 79 mg (75%). H NMR: δ 2.28
(s, 3H, CH3), 2.88 (s, 6H, NCH3), 6.70 (d, J = 8.7 Hz, 2H, C6H4),
7.11 (d, J = 7.8 Hz, 2H, C6H4), 7.35−7.41 (m, 4H, C6H4). 13C{1H}
NMR: δ 21.2, 40.8, 113.0, 126.3, 127.7, 129.5, 135.7, 138.5, 149.9.
(4′-Methylbiphenyl-4-yl)(phenyl)methanone.18 Eluent: petroleum
ether/ethyl acetate = 100:1; yield 120 mg (88%). 1H NMR: δ 2.31 (s,
3H), 7.18 (d, J = 7.8 Hz, 2H), 7.36−7.51 (m, 5H, C6H4), 7.58 (d, J =
8.4 Hz, 2H), 7.71−7.79 (m, 4H). 13C{1H} NMR: δ 21.3, 126.8, 127.2,
128.4, 129.8, 130.1, 130.8, 132.4, 136.1, 137.2, 138.0, 138.3, 145.3,
196.4.
N,N-Diethyl-4′-methoxybiphenyl-4-carboxamide.16 Eluent: petro-
leum ether/ethyl acetate = 8:1; yield 137 mg (97%). 1H NMR: δ 1.17
(b, 6H), 3.31 (b, 2H), 3.50 (b, 2H,), 3.79 (s, 3H), 6.94 (d, J = 8.7 Hz,
2H), 7.40 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.1
Hz, 2H). 13C{1H} NMR: δ 13.0, 14.2, 39.1, 43.0, 55.0, 114.2, 126.4,
126.8, 128.0, 132.7, 135.4, 141.5, 159.4, 171.1.
4-Trifluoromethyl-4′-methoxybiphenyl.3h Eluent: petroleum
1
ether; yield 114 mg (90%). H NMR: δ 3.88 (s, 3H), 7.02 (d, J =
8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.67 (s, 4H). 13C{1H} NMR: δ
55.5, 114.6, 124.6 (q, J = 271.9 Hz), 125.8 (q, J = 3.9 Hz), 127.0,
128.5, 128.8 (q, J = 32.4 Hz), 132.3, 144.3, 160.0.
Ethyl 4′-Methylbiphenyl-4-carboxylate.18 Eluent: petroleum
1
ether/ethyl acetate = 120:1; yield 97 mg (81%). H NMR: δ 1.32
(t, J = 7.2 Hz, 3H), 2.32 (s, 3H), 4.31 (q, J = 7.2 Hz, 2H), 7.18 (d, J =
8.1 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 8.01
(d, J = 8.4 Hz, 2H). 13C{1H} NMR: δ 14.5, 21.3, 61.0, 126.9, 127.2,
129.1, 129.8, 130.2, 137.3, 138.2, 145.6, 166.7.
4-Methoxy-2′-methylbiphenyl.16 Eluent: petroleum ether; yield 74
mg (75%). 1H NMR: δ 2.27 (s, 3H), 3.84 (s, 3H), 6.94 (d, J = 8.7 Hz,
2H), 7.21−7.26 (m, 6H). 13C{1H} NMR: δ 20.7, 55.4, 113.6, 125.9,
127.1, 130.0, 130.4, 130.4, 134.5, 135.6, 141.7, 158.7.
N,N-Diethyl-4′-methylbiphenyl-4-carboxamide.18 Eluent: petrole-
4′-Methoxy-N,N-dimethylbiphenyl-4-amine.16 Eluent: petroleum
ether/ethyl acetate = 100:1; yield 109 mg (96%). 1H NMR: δ 2.99 (s,
6H), 3.85 (s, 3H), 6.83 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H),
7.45−7.51 (m, 4H). 13C{1H} NMR: δ 40.9, 55.5, 113.2, 114.3, 127.5,
134.1, 149.7, 158.4.
1
um ether/ethyl acetate = 8:1; yield 131 mg (98%). H NMR: δ 1.18
(b, 6H), 2.38 (s, 3H), 3.32 (b, 2H), 3.52 (b, 2H), 7.23 (d, J = 8.0 Hz,
2H), 7.42 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.1
Hz, 2H). 13C{1H} NMR: δ 12.8, 14.2, 21.0, 39.2, 43.2, 126.7, 126.8,
129.5, 135.6, 137.4, 141.8, 171.0.
N,N-Dimethyl-4-(naphthalen-1-yl)aniline.3h Eluent: petroleum
(4′-Methylbiphenyl-2-yl)(phenyl)methanone.19 Eluent: petroleum
ether/ethyl acetate = 100:1; yield 121 mg (89%). 1H NMR: δ 2.12 (s,
3H), 6.89 (d, J = 7.8 Hz, 2H), 7.05 (d, J = 8.1 Hz, 2H), 7.15 (t, J = 7.8
Hz, 2H), 7.26−7.46 (m, 5H), 7.56 (d, J = 7.2 Hz, 2H). 13C{1H} NMR:
δ 21.1, 126.8, 128.2, 128.7, 128.9, 129.1, 130.0, 130.2, 130.3, 132.9,
137.1, 137.4, 137.5, 139.0, 141.2, 198.8.
ether/ethyl acetate = 100:1; yield 115 mg (93%). H NMR: δ 2.85
1
(s, 6H), 6.71 (d, J = 8.7 Hz, 2H), 7.25−7.38 (m, 6H), 7.65 (d, J = 7.9
Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H). 13C{1H}
NMR: δ 40.7, 112.5, 125.6, 125.7, 125.8, 126.5, 126.9, 127.0, 128.4,
129.0, 131.0, 132.1, 134.1, 140.6, 149.9.
Methyl 4′-(Dimethylamino)biphenyl-2-carboxylate.20 Eluent: pe-
Methyl 2-(p-tolyl)benzoate.20 Eluent: petroleum ether/ethyl
acetate = 120:1; yield 113 mg (86%). 1H NMR: δ 2.28 (s, 3H),
3.55 (s, 3H), 7.10 (s, 4H), 7.26 (t, J = 6.9 Hz, 2H), 7.36−7.41 (m,
1H), 7.69 (d, J = 6.9 Hz, 1H). 13C{1H} NMR: δ 21.2, 51.9, 127.0,
128.3, 128.9, 129.8, 130.8, 131.0, 131.2, 136.9, 138.4, 142.5, 169.3.
2-(p-Tolyl)benzaldehyde.19 Eluent: petroleum ether/ethyl acetate
troleum ether/ethyl acetate = 60:1; yield 102 mg (80%). H NMR: δ
1
2.97 (s, 6H), 3.68 (s, 3H), 6.75 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.7
Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.37 (d, J = 7.5 Hz, 1H), 7.46 (t, J =
7.2 Hz, 1H), 7.73 (d, J = 7.5 Hz, 1H). 13C{1H} NMR: δ 40.9, 52.0,
112.2, 126.2, 129.1, 129.2, 129.6, 130.6, 130.9, 131.1, 142.4, 149.9,
170.0.
= 100:1; yield 91 mg (93%). H NMR: δ 2.34 (s, 3H), 7.19 (s, 4H),
4′-(Dimethylamino)-N,N-diethylbiphenyl-4-carboxamide.20 Elu-
1
1
7.33−7.40 (m, 2H), 7.53 (dt, J = 1.5, 7.5 Hz, 1H), 7.94 (dd, J = 1.2,
7.8 Hz, 1H), 9.90 (s, 1H). 13C{1H} NMR: δ 21.3, 127.7, 127.7, 129.3,
130.1, 130.9, 133.6, 133.9, 134.9, 138.2, 146.1, 192.7.
ent: petroleum ether/ethyl acetate = 4:1; yield 144 mg (97%). H
NMR: δ 1.19 (b, 6H), 3.00 (s, 6H), 3.37 (b, 2H), 3.48 (b, 2H), 6.80
(d, J = 8.8 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H),
7.57 (d, J = 8.2 Hz, 2H). 13C{1H} NMR: δ 13.0, 14.0, 39.4, 40.5, 43.1,
112.8, 126.0, 126.9, 127.7, 128.2, 134.7, 142.1, 150.3, 171.5.
2-p-Tolylpyridine.16 Eluent: petroleum ether/ethyl acetate = 30:1;
yield 84 mg (99%). 1H NMR: δ 2.38 (s, 3H), 7.11−7.19 (m, 1H), 7.26
(d, J = 8.1 Hz, 2H), 7.67 (d, J = 3.6 Hz, 2H), 7.88 (d, J = 8.1 Hz, 2H),
8.66 (d, J = 4.8 Hz, 1H). 13C{1H} NMR: δ 21.2, 120.3, 121.8, 126.8,
129.5, 136.7, 139.0, 149.7, 157.5.
2-(4-(Trifluoromethyl)phenyl)pyridine.24 Eluent: petroleum ether/
1
ethyl acetate = 30:1; yield 104 mg (93%). H NMR: δ 7.28−7.32 (m,
1H), 7.72−7.83 (m, 4H), 8.11 (d, J = 8.1 Hz, 2H), 8.73 (d, J = 4.8 Hz,
1H). 13C{1H} NMR: δ 120.9, 123.1, 124.4 (q, J = 272.2 Hz), 125.8 (q,
J = 3.9 Hz), 127.3, 130.9 (q, J = 32.4 Hz), 137.1, 142.8, 150.1, 156.0.
3-(4-(Trifluoromethyl)phenyl)pyridine.25 Eluent: petroleum ether/
3-p-Tolylpyridine.21 Eluent: petroleum ether/ethyl acetate = 30:1;
yield 84 mg (99%). 1H NMR: δ 2.39 (s, 3H), 7.26 (d, J = 7.8 Hz, 2H),
7.28−7.33 (m, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.80−7.84 (m, 1H), 8.55
(dd, J = 1.5, 4.8 Hz, 1H), 8.83 (dd, J = 0.9, 2.4 Hz, 1H). 13C{1H}
NMR: δ 20.8, 123.5, 127.0, 129.8, 134.1, 135.0, 136.6, 138.0, 148.2.
1-(4-Methoxyphenyl)naphthalene.5a Eluent: petroleum ether;
1
ethyl acetate = 8:1; yield 84 mg (76%). H NMR: δ 7.41−7.47 (m,
1H), 7.70 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H), 7.91 (d, J = 6
Hz, 1H), 8.67 (s, 1H), 8.88 (s, 1H). 13C{1H} NMR (75 MHz,
CDCl3): δ 115.8, 123.9, 124.2 (q, J = 272.2 Hz), 126.2 (q, J = 3.8 Hz),
127.6, 130.4 (q, J = 32.6 Hz), 134.7, 135.5, 141.4, 148.3, 149.3.
2-o-Tolylpyridine.26 Eluent: petroleum ether/ethyl acetate = 30:1;
yield 80 mg (94%). 1H NMR: δ 2.40 (s, 3H), 7.26−7.34 (m, 3H), 7.47
1
yield 98 mg (84%). H NMR: δ 3.73 (s, 3H), 6.89 (d, J = 8.6 Hz,
2H), 7.26−7.39 (m, 6H), 7.68−7.83 (m, 3H). 13C{1H} NMR: δ 55.4,
113.8, 125.5, 125.8, 126.0, 126.2, 127.0, 127.5, 128.4, 131.2, 131.9,
133.2, 134.0, 140.0, 159.1.
4290
dx.doi.org/10.1021/jo500619f | J. Org. Chem. 2014, 79, 4285−4292

The Journal of Organic Chemistry
Featured Article
(d, J = 8.1 Hz, 2H), 7.83 (d, J = 8.1 Hz, 1H), 8.55 (d, J = 3.3 Hz, 1H),
8.83 (d, J = 1.5 Hz, 1H). 13C{1H} NMR: δ 20.3, 121.6, 124.2, 125.9,
128.3, 129.7, 130.8, 135.8, 136.2, 140.5, 149.2, 160.1.
(m, 2H). 13C{1H} NMR: δ 108.6, 111.7, 115.4 (d, J = 23.3 Hz), 117.3
(d, J = 21.8 Hz), 125.5 (d, J = 3.5 Hz), 128.6, 128.9 (d, J = 8 Hz),
129.8, 133.6, 136.6, 138.8 (d, J = 6.3 Hz), 142.7, 151.0, 163.8 (d, J =
251.3 Hz), 196.8. 19F{1H} NMR: δ −113.17. HR-MS: m/z 266.0737
[M]+, calcd for C17H11FO2 266.0743.
2-(Naphthalen-1-yl)pyridine.27 Eluent: petroleum ether/ethyl
1
acetate = 30:1; yield 94 mg (92%). H NMR: δ 7.24−7.29 (m, 1H),
(2-Benzyl-5-fluorophenyl)(phenyl)methanone. Eluent: petroleum
7.41−7.47 (m, 2H), 7.49−7.59 (m, 3H), 7.75 (dt, J = 1.8, 7.8 Hz, 1H),
7.87 (d, J = 9 Hz, 2H), 8.04−8.09 (m, 1H), 8.76−8.78 (m, 1H).
13C{1H} NMR: δ 122.0, 125.1, 125.3, 125.6, 125.9, 126.5, 127.5, 128.4,
128.9, 131.2, 134.0, 136.4, 138.5, 149.5, 159.3.
1
ether/ethyl acetate = 100:1; light yellow oil, yield 89 mg (61%). H
NMR (400 MHz, CDCl3): δ 3.99 (s, 2H), 6.99−7.06 (m, 3H), 7.08−
7.13 (m, 2H), 7.14−7.19 (m, 2H), 7.21−7.25 (m, 1H), 7.41 (t, J = 7.6
Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.70−7.73 (m, 2H). 13C{1H} NMR:
δ 38.2, 115.4 (d, J = 22.7 Hz), 117.3 (d, J = 20.9 Hz), 126.3, 128.5,
128.6, 129.2, 130.3, 132.6 (d, J = 7.6 Hz), 133.7, 135.9 (d, J = 3.5 Hz),
137.1, 140.3, 140.4 (d, J = 5.9 Hz), 160.6 (d, J = 248.1 Hz), 197.2.
19F{1H} NMR: δ −116.26. HR-MS: m/z 290.1057 [M]+, calcd for
C20H16FO 290.1107.
(2-(Furan-2-yl)phenyl)(phenyl)methanone. Eluent: petroleum
ether/ethyl acetate = 100:1; pale yellow liquid, yield 113 mg (91%).
1H NMR: δ 6.26 (s, 1H), 6.42 (d, J = 3.2 Hz, 1H), 7.23 (s, 1H), 7.34−
7.40 (m, 4H), 7.48−7.55 (m, 2H), 7.72−7.77 (m, 3H) . 13C{1H}
NMR: δ 108.8, 111.7, 126.7, 127.5, 128.3, 128.5, 129.1, 129.8, 130.1,
133.2, 137.0, 137.2, 142.8, 151.9, 198.5. HR-MS: m/z 249.0916 [M +
H]+, calcd for C17H13O2 249.0903.
N,N-Dimethyl-[1,1′:4′,1″-terphenyl]-4-amine.34 Eluent: petroleum
ether/ethyl acetate = 100:1; yield 112 mg (82%). 1H NMR: δ 3.00 (s,
6H), 6.83 (d, J = 8.1 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.2
Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H,), 7.63 (s, 6H). 13C{1H} NMR: δ
40.9, 113.2, 126.7, 127.1, 127.2, 127.5, 127.8, 128.9, 139.0, 140.3,
141.1.
2-(4-(Trifluoromethyl)phenyl)furan.28 Eluent: petroleum ether;
1
yield 56 mg (53%). H NMR: δ 6.48−6.50 (m, 1H), 6.74 (d, J =
3.3 Hz, 1H), 7.50 (s, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.2 Hz,
2H). 13C{1H} NMR: δ 107.1, 112.1, 123.9, 124.4 (q, J = 272 Hz),
125.8 (q, J = 3.9 Hz), 129.1 (q, J = 33.1 Hz), 134.0, 143.2, 152.7.
2-(Furan-2-yl)pyridine.29 Eluent: petroleum ether/ethyl acetate =
30:1; yield 125 mg (86%). 1H NMR: δ 6.50−6.51 (m, 1H), 7.04 (d, J
= 3.3 Hz, 1H), 7.09−7.13 (m, 1H), 7.50 (d, J = 0.9 Hz, 1H), 7.65−
7.68 (m, 2H), 8.57 (d, J = 4.8 Hz, 1H). 13C{1H} NMR: δ 108.7, 112.2,
118.7, 122.0, 136.7, 143.4, 149.5, 149.7, 153.7.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H, 13C, and 19F NMR spectra of the cross-coupling
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(2-Benzylphenyl)(phenyl)methanone.30 Eluent: petroleum ether/
1
ethyl acetate = 30:1; yield 120 mg (88%). H NMR: δ 3.96 (s, 2H),
6.97−6.99 (m, 3H), 7.04−7.08 (m, 2H), 7.13−7.20 (m, 3H), 7.26−
7.31 (m, 3H), 7.42 (t, J = 7.6 Hz, 1H), 7.62 (d, J = 7.2 Hz, 2H).
13C{1H} NMR: δ 38.9, 125.7, 126.1, 128.36, 128.39, 128.7, 129.3,
130.2, 130.4, 130.9, 133.2, 137.7, 138.9, 140.2, 140.5, 198.6.
AUTHOR INFORMATION
Corresponding Author
*E-mail: zxwang@ustc.edu.cn.
Notes
■
2-Benzylpyridine.31 Eluent: petroleum ether/ethyl acetate = 30:1;
1
yield 78 mg (92%). H NMR: δ 4.06 (s, 2H), 6.96−7.00 (m, 2H),
The authors declare no competing financial interest.
7.08−7.22 (m, 5H), 7.41−7.47 (m, 1H), 8.44 (d, J = 4.6 Hz, 1H).
13C{1H} NMR: δ 44.8, 121.3, 123.1, 126.4, 128.6, 129.2, 136.5, 139.5,
149.4, 161.0.
ACKNOWLEDGMENTS
■
This research was supported by the National Basic Research
Program of China (Grant No. 2009CB825300) and the
National Natural Science Foundation of China (Grant No.
21172208).
Phenyl(p-tolyl)methanone.32 Eluent: petroleum ether/ethyl ac-
etate = 100:1; yield 79 mg (81%). 1H NMR: δ 2.34 (s, 3H), 7.18 (d, J
= 8.1 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.48 (t, J = 7.4 Hz, 1H), 7.63
(d, J = 8.1 Hz, 2H), 7.67−7.70 (m, 2H). 13C{1H} NMR: δ 21.7, 128.3,
129.1, 130.0, 130.4, 132.2, 134.9, 138.0, 143.3, 196.6.
Phenyl(o-tolyl)methanone.33 Eluent: petroleum ether/ethyl ac-
etate = 100:1; yield 97 mg (99%). 1H NMR: δ 2.24 (s, 3H), 7.12−7.23
(m, 3H), 7.27−7.32 (m,1H), 7.35 (t, J = 7.5 Hz, 2H), 7.48 (t, J = 7.4
Hz, 1H), 7.69−7.72 (m, 2H). 13C{1H} NMR: δ 20.1, 125.3, 128.5,
128.6, 130.2, 130.3, 131.1, 133.2, 136.8, 137.9, 138.8, 198.7.
1,4-Di(p-methylphenyl)benzene.5a Eluent: petroleum ether; yield
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Eur. J. 2012, 18, 446. (c) Ackermann, L.; Born, R.; Spatz, J. H.; Meyer,
1
101 mg (78%). H NMR: δ 2.40 (s, 6H), 7.26 (d, J = 7.8 Hz, 4H),
7.53 (d, J = 7.9 Hz, 4H), 7.64 (s, 4H). 13C{1H} NMR: δ 21.3, 127.0,
127.4, 129.7, 137.2, 138.1, 139.9.
1,3,5-Tris(4′-methoxyphenyl)benzene.32 Eluent: petroleum ether/
1
ethyl acetate = 20:1; yield 159 mg (80%). H NMR: δ 3.83 (s, 9H),
6.99 (d, J = 8.7 Hz, 6H), 7.60 (d, J = 8.7 Hz, 6H), 7.64 (s, 3H).
13C{1H} NMR: δ 55.5, 114.4, 124.2, 128.5, 134.0, 142.0, 159.4.
(4-Fluoro-4′-methylbiphenyl-2-yl)(phenyl)methanone. Eluent:
petroleum ether/ethyl acetate = 100:1; light yellow oil, yield 123 mg
(85%). 1H NMR: δ 2.15 (s, 3H), 6.91 (d, J = 8 Hz, 2H), 7.03 (d, J = 8
Hz, 2H), 7.09−7.18 (m, 2H), 7.21 (t, J = 7.8 Hz, 2H), 7.33−7.37 (m,
2H), 7.58 (d, J = 7.2 Hz, 2H). 13C{1H} NMR: δ 21.1, 115.6 (d, J =
22.9 Hz), 117.3 (d, J = 21.2 Hz), 128.3, 128.9, 129.2, 130.1, 132.0 (d, J
= 7.7 Hz), 133.3, 136.3, 136.8, 137.26, 137.29, 140.5 (d, J = 6.3 Hz),
161.6 (d, J = 249.5 Hz), 197.4. 19F{1H} NMR: δ −115.12. HR-MS: m/
z 290.1101 [M]+, calcd for C20H15FO 290.1107.
(5-Fluoro-2-(furan-2-yl)phenyl)(phenyl)methanone. Eluent: pe-
troleum ether/ethyl acetate = 100:1; light yellow oil, yield 105 mg
(79%). 1H NMR: δ 6.24 (dd, J = 1.8, 3.4 Hz, 1H), 6.34−6.35 (m,1H),
7.10 (dd, J = 2.6, 8.4 Hz, 1H), 7.20−7.25 (m, 2H), 7.35−7.39 (m,
2H), 7.48−7.53 (m, 1H), 7.70 (dd, J = 5.2, 8.7 Hz, 1H), 7.73−7.76
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