Catalytic electrochemical C-H iodination and one-pot arylation by ON/OFF switching of electric current

Article abstract of DOI:10.1021/jo3012286

Palladium-catalyzed electrochemical iodination and one-pot arylation of arylpyridines are described. Ortho-selective C-H iodination proceeded via dual activation of each substrate by a palladium catalyst and an electrode. Various aryl groups were introduc

Full text of DOI:10.1021/jo3012286

Note
pubs.acs.org/joc
Catalytic Electrochemical C−H Iodination and One-Pot Arylation by
ON/OFF Switching of Electric Current
Hiroko Aiso, Takuya Kochi, Hitoshi Mutsutani, Takamasa Tanabe, Shigeru Nishiyama,
and Fumitoshi Kakiuchi*
Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa
223-8522, Japan
S
* Supporting Information
ABSTRACT: Palladium-catalyzed electrochemical iodination and
one-pot arylation of arylpyridines are described. Ortho-selective C−
H iodination proceeded via dual activation of each substrate by a
palladium catalyst and an electrode. Various aryl groups were
introduced at the ortho positions of arylpyridines by ON/OFF
switching of two different catalytic cycles using the same palladium
catalyst in a one-pot fashion.
etal-catalyzed cross-coupling between aryl halides and
Morganometallic reagents is one of the most important
methods for efficient synthesis of functionalized aromatic
compounds.1 However, these methods require preinstallation
of reactive carbon−halogen bonds precisely at the bond-
forming sites, which may become cumbersome depending on
the substrate structure. In this context, catalytic regioselective
halogenation of arenes via chelation-assisted C−H bond
cleavage has attracted much attention in recent years.2−5 Our
group has reported that ortho-selective chlorination and
bromination of arenes proceeds using a combination of
palladium-catalyzed C−H bond cleavage and electrochemical
oxidation.6,7 Because halonium ions can be generated in situ as
active halogenating agents from inexpensive, stable aqueous
HCl and HBr solutions, the reaction does not require the
addition of more than 1 equiv of halogenating agents with
strong oxidizing ability. This method offers relatively clean
environments in the reaction vessels because generation of the
halogenating agent can be halted by simply turning off the
electricity.
The controllability of generation of halogenating agents led
us to investigate one-pot halogenation/cross-coupling reaction
Figure 1. One-pot C−H halogenation/Suzuki−Miyaura coupling by
(Figure 1). The palladium-catalyzed electrochemical C−H
halogenation is considered to proceed via a Pd(II)/Pd(IV) or
Pd(II)/Pd(III) catalytic cycle (Cycle A).2a,4,8,9 A palladacycle
formed after chelation-assisted C−H bond cleavage reacts with
an electrochemically generated halonium ion to provide aryl
halides. After the halogenation, if the electricity is turned off,
the formation of unstable halonium ions would stop, allowing
the reaction system to be free of strong oxidants. Therefore, we
speculated that it would become possible to generate Pd(0)
species,10 which can cleave the newly formed carbon−halogen
bonds and may be further used for cross-coupling reactions
such as widely applicable Suzuki−Miyaura coupling (Cycle B).
In this way, ON/OFF switching of electricity may be used to
employ a palladium catalyst for two different catalytic cycles, a
ON/OFF switching of electric current.
Pd(II)/Pd(IV) or Pd(II)/Pd(III) cycle9 and a Pd(0)/Pd(II)
cycle, in an one-pot fashion.
To achieve this goal, we first developed a palladium-catalyzed
electrochemical ortho-selective iodination of arenes, because
carbon−iodine bonds are regarded as the most reactive
carbon−halogen bonds in cross-coupling. By applying this
iodination method, we succeeded in one-pot Suzuki−Miyaura
Received: June 20, 2012
Published: August 12, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
coupling, which enables the introduction of various aryl groups
at ortho-positions.
desired product was not observed until the electricity was
passed for 1.5 h, which means that more than 2 F/mol of
electricity was consumed (ca. 2.2 F/mol). When 4 equiv of
potassium iodide was used with a 10 or 5 mA electric current,
the observed induction periods were 2.5 or 5 h, respectively,
which corresponds to ca. 4 F/mol of electricity in each case.
These results show that there is a strong correlation between
the amounts of potassium iodide and the electricity consumed
during the induction period, which essentially matches the time
required to convert all the iodide ion to I2 (1 F/mol is
necessary for the conversion of 1 equiv of iodide ion to 0.5
equiv of I2).
We initiated our efforts to develop catalytic electrochemical
C−H iodination by screening reaction conditions using 2-(o-
tolyl)pyridine (1a) as a substrate. As an initial attempt, aqueous
HI solution, instead of an HCl or HBr solution, was used under
the previously reported electrochemical C−H halogenation
conditions,6 but the desired iodination product 2a was not
observed (Table 1, entry 1). Next, separate addition of iodine
Table 1. Optimization of Palladium-Catalyzed
Electrochemical Ortho C−H Iodination of Arylpyridine 1a
a
The results of the GC monitoring led us to examine the
electrochemical C−H iodination using I2 as an iodine source
(Table 1, entries 5−8). As expected, when the reaction was
performed with 2 equiv of I2 and a 5 mA electric current, no
induction period was observed and 2a was obtained in 88%
yield using only 2.6 F/mol of electricity (entry 5).11 The result
suggests that iodonium ion, generated from I2 by electro-
chemical oxidation, is the active iodinating agent in the C−H
iodination. Yoshida and co-workers have reported the electro-
chemical generation of iodonium ion in acetonitrile, and
applied it for electrophilic iodination of arenes.12,13 Extension
of the reaction time to 4.5 h slightly improved the product yield
to 89% (entry 6). The electrochemical C−H iodination can
also be performed with 1 equiv of I2 to afford 79% yield of 2a
(entry 7). When the reaction was conducted with a 2.5 mA
electric current, the reaction became slower (see the
Supporting Information) but 88% yield of 2a was obtained
using only 2.1 F/mol of electricity (entry 8). As a result, the
reaction conditions using 2 equiv of I2 with a 5 mA electric
current were chosen as standard conditions for the screening of
substrates.
entry iodine source
HX
I (mA) time (h) F/mol yield (%)
b
c
1
2
3
4
5
6
7
8
-
HI
20
10
10
5
9.0
5.5
27
8.2
10
7.8
nd
71
2 equiv KI
4 equiv KI
4 equiv KI
2 equiv I2
2 equiv I2
1 equiv I2
2 equiv I2
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
7.0
85
83
88
89
79
88
10.5
3.5
5
2.6
3.4
3.4
2.1
5
4.5
5
4.5
2.5
5.5
a
Reaction conditions: 1a (0.25 mmol), Pd(OAc)2 (10 mol %), iodine
source, acetonitrile (10 mL) [anode], and 0.2 M H2SO4 aq [cathode]
in an H-type divided cell with two platinum electrodes and an anion-
b
exchange membrane, 90 °C. A 2 M aqueous solution of HI was used.
c
Not detected.
The electrochemical C−H iodination was then investigated
using various arylpyridines (Table 2). The reaction of
arylpyridine 1b bearing an electron-withdrawing trifluorometh-
yl group at an ortho position for 11 h at a 10 mA provided
iodination product 2b in 79% yield (entry 1). The C−H
iodination is also applicable to substrates with a 3-methyl-2-
source and electrolyte was considered. When potassium iodide
and sulfuric acid, both stable, inexpensive reagents, were used as
an iodine source and an electrolyte, the iodination reaction
proceeded and aryl iodide 2a was obtained. When 2 equiv of
potassium iodide was used with a 10 mA electric current, 2a
was obtained in 71% yield, but 5.5 h and 8.2 F/mol of
electricity were necessary to complete the reaction (entry 2).
Although increase of the amount of potassium iodide led to
improvement in yield, it did not reduce the reaction time nor
the amount of electricity (entry 3). Decrease of the electric
current to 5 mA further elongated the reaction time (entry 4).
Electrochemical C−H iodination using potassium iodide was
taken under close examination by GC, and it revealed that there
were induction periods prior to the initiation of the iodination
reaction (Figure 2). When the reaction was carried out with 2
equiv of potassium iodide and a 10 mA electric current, the
Table 2. Palladium-Catalyzed Electrochemical Ortho C−H
a
Iodination of Arylpyridines
I
time
(h)
F/
mol
yield
(%)
entry
1
R1
R2
(mA)
2
b
1
1b
1c
1d
1e
1f
H
o-CF3
H
10
5
11
4
16
2b
2c
2d
2e
2f
79
70
85
75
61
70
64
2
3
4
Me
Me
Me
Me
Me
Me
3.0
3.7
2.6
7.8
16
p-Me
m-Me
p-F
5
5
5
3.5
10.5
11
9.5
c
5
5
b
6
1g
1h
p-CF3
m-CF3
10
5
2g
2h
d
7
7.1
a
Reaction conditions: 1 (0.25 mmol), Pd(OAc)2 (10 mol %), I2 (2
equiv), acetonitrile (10 mL) [anode], and 0.2 M H2SO4 aq [cathode]
in an H-type divided cell with two platinum electrodes and an anion-
b
exchange membrane, 90 °C, 5 mA. Performed with 8 equiv of I2 at 10
c
d
mA. Performed with 4 equiv of I2. Performed with 20 mol % of
Pd(OAc)2 and 10 equiv of I2.
Figure 2. Plot of yield of 2a versus time.
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The Journal of Organic Chemistry
Note
pyridyl directing group. 3-Methyl-2-phenylpyridine (1c)
possesses two ortho hydrogens, but only the less hindered
one was iodinated to give 2c in 70% yield (entry 2). Substrates
with p- and m-tolyl groups (1d,e) also gave monoiodination
product 2d and 2e in 85 and 75% yields, respectively (entries 3
and 4). Arylpyridines with fluoro and trifluoromethyl groups
(1f−h) required more forcing conditions, but the correspond-
ing monoiodination products 2f−h were obtained in 61−70%
yields (entries 5−7). Further investigation on the substrates
showed that a substituent at the 3-position of the pyridine ring
or the ortho position on the benzene ring was necessary to
achieve high yield of the iodination product by our catalytic
electrochemical C−H iodination.
observed in this case. Phenylboronic acid can also be present in
the reaction system from the start of the one-pot process (entry
5). The C−H iodination in the presence of phenylboronic acid,
followed by addition of potassium carbonate, also gave 3a in
78% yield.
This one-pot electrochemical C−H iodination/arylation
process can be performed with various substrates (Table 4).
Table 4. One-Pot Ortho C−H Iodination/Arylation of
a
Arylpyridines
Next, we examined the one-pot electrochemical C−H
iodination/Suzuki−Miyaura coupling (Table 3). As an initial
Table 3. Optimization of Palladium-Catalyzed
Electrochemical Ortho C−H Iodination of Arylpyridine 1a
a
entry
1
R1
R2
Ar
3
yield (%)
1
1c
1d
1e
1a
1a
1a
1a
1a
1a
1a
1d
1a
1a
1a
Me
Me
Me
H
H
Ph
Ph
Ph
3b
3c
3d
3e
3f
70
84
73
67
81
76
74
69
82
63
66
63
53
58
2
p-Me
m-Me
o-Me
o-Me
o-Me
o-Me
o-Me
o-Me
o-Me
p-Me
o-Me
o-Me
o-Me
3
4
o-MeC6H4
m-MeC6H4
p-MeC6H4
p-nPentC6H4
p-iPrC6H4
p-tBuC6H4
p-MeOC6H4
p-MeOC6H4
p-FC6H4
5
H
6
H
3g
3h
3i
7
H
electric current ON
time
electric current OFF
yields (%)
8
H
time
(h)
9
H
3j
entry
reagent
(h)
reagent
2a
85
3a
10
11
12
13
14
H
3k
3l
b
1
2
3
4
PhB(OH)2
4.5
4.5
4.5
4.5
-
-
-
2
2
2
nd
nd
nd
Me
H
b
b
c
PhB(OH)2
84
3m
3n
3o
-
-
PhB(OH)2
86
H
p-CF3C6H4
p-BrC6H4
b
PhB(OH)2,
K2CO3
nd
84
H
a
b
c
Reaction conditions: 1a (0.25 mmol), Pd(OAc)2 (10 mol %), I2 (0.5
5
PhB(OH)2
4.5
K2CO3
2
nd
78
a
mmol), acetonitrile (10 mL) [anode], and 0.2 M H2SO4 aq [cathode]
in an H-type divided cell with two platinum electrodes and an anion-
exchange membrane, 90 °C, 5 mA, 3.5−4.5 h, and then ArB(OH)2
(0.75 mmol) and K2CO3 (0.75 mmol) [anode], and K2CO3 (2.5
mmol) [cathode], 90 °C, 2 h without electric current.
Reaction conditions: 1a (0.25 mmol), Pd(OAc)2 (10 mol %), I2 (0.5
mmol), acetonitrile (10 mL), PhB(OH)2 (0.75 mmol, if added)
[anode], and 0.2 M H2SO4 aq [cathode] in an H-type divided cell with
two platinum electrodes and an anion-exchange membrane, 90 °C, 5
mA, 4.5 h, and then PhB(OH)2 (0.75 mmol, if added) and K2CO3
(0.75 mmol, if added) [anode], and K2CO3 (2.5 mmol, if added)
b
c
[cathode], 90 °C, 2 h without electric current. Not detected. Yield
determined by the H NMR integral ratio of the purified material.
Arylpyridines 1c−e were phenylated to give 3b−d in high
yields (entries 1−3). Introduction of o-, m-, and p-tolyl groups
to 1a can be conducted to provide arylation products 3e−g in
high yields (entries 4−6). Particularly, o-tolylboronic acid has
not been reported to be used for the direct C−H arylation of
arylpyridines.17 In addition to methyl group, arylboronic acids
bearing n-pentyl, isopropyl, and tert-butyl substituents were also
used for the one-pot arylation, and the corresponding products
3h−j were obtained in 69−82% yields (entries 7−9). Both
electron-donating and -withdrawing groups such as methoxy,
trifluoromethyl, and fluoro groups were tolerated to give the
arylation products 3k−n (entries 10−13). The one-pot
arylation using p-bromophenylboronic acid was also possible,
and the corresponding arylation product 3o bearing a bromo
group was obtained in 58% yield (entry 14).
1
attempt, electrochemical C−H iodination was performed in the
presence of phenylboronic acid, but only iodination proceeded
to give 2a in 85% yield, and no arylation product was observed
(entry 1). With the former result in hand, electrochemical C−H
iodination was performed in the same manner with phenyl-
boronic acid, and then the generation of iodonium ion was
stopped by turning off the electricity, and the mixture was
heated for an additional 2 h, only to give 2a in a similar yield
(entry 2). An experiment following the same protocol except
that phenylboronic acid was added after the electric current was
halted also gave a similar result (entry 3). Addition of a base
was then investigated because bases are generally necessary for
Suzuki−Miyaura coupling to proceed.1a,b,14 Finally, electro-
chemical C−H iodination, followed by addition of phenyl
boronic acid and potassium carbonate and heating without
supplying additional electric current, provided phenylation
product 3a in 84% yield (entry 4).15,16 No remaining 2a was
In summary, palladium-catalyzed electrochemical iodination
and one-pot arylation of arylpyridines were achieved. Using I2
as an iodine source, ortho-selective C−H iodination proceeded
via dual activation of each substrate by a palladium catalyst and
an electrode. Various aryl groups were introduced at the ortho-
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The Journal of Organic Chemistry
Note
1H NMR spectroscopic data are in good agreement with those
reported in literature.2d
positions of arylpyridines by the one-pot arylation process,
taking advantage of the wide generality of Suzuki−Miyaura
coupling. The ON/OFF switching of two different catalytic
cycles, a Pd(II)/Pd(IV) or Pd(II)/Pd(III) cycle and a Pd(0)/
Pd(II) cycle, was also accomplished using the same palladium
catalyst in a one-pot fashion. This one-pot arylation method
employs only simple, easily accessible reagents and may be
regarded as a convenient way to obtain arylation products.
2-(2-Iodo-4-methylphenyl)-3-methylpyridine (2d). General
procedure A was followed with 46.3 mg (0.253 mmol) of 3-methyl-
2-(4-methylphenyl)pyridine (1d), prepared according to the proce-
dure reported by Queguiner and co-workers,20 and the reaction was
carried out under a 5 mA constant current condition for 3.5 h. Column
chromatography (silica gel 60N, 100:1 CH2Cl2/EtOAc) afforded 66.6
1
mg of 2d (0.215 mmol, 85% yield) as a colorless oil: H NMR (400
MHz, CDCl3) δ 2.13 (s, 3H), 2.36 (s, 3H), 7.13 (d, J = 7.8 Hz, 1H),
7.22−7.25 (m, 2H), 7.58 (d, J = 7.3 Hz, 1H), 7.77 (s, 1H), 8.52 (d, J =
4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 19.1, 20.6, 97.5, 122.8,
128.8, 129.0, 131.5, 137.8, 139.3, 139.4, 142.4, 146.5, 160.9; IR (neat)
2361 (w), 1737 (w), 1698 (w), 1655 (w), 1600 (s), 1568 (m), 1490
(m), 1439 (s), 1380 (m), 1256 (w), 1184 (w), 1118 (m), 1072 (m),
1054 (w), 1014 (m), 823 (s), 791 (s), 682 (w), 666 (w), 587 (m), 568
(w) cm−1; MS m/z (% relative intensity), 310 (8, M+), 309 (55), 183
(14), 182 (100), 181 (24), 180 (19), 168 (10), 167 (75), 166 (12),
152 (9), 140 (7), 139 (8), 91 (19), 90 (15), 89 (12), 84 (23), 77 (12),
76 (7), 65 (8), 64 (6), 63 (14); HRMS (ESI-TOF) calcd for [M + H]+
(C13H13IN) m/z 310.0093, found 310.0099.
EXPERIMENTAL SECTION
■
General Procedure A for Electrochemical Iodination using
I2. The electrochemical oxidation was carried out in an H-type divided
cell (anion-exchange membrane) equipped with two platinum
electrodes (1.7 × 1.7 cm2). The anodic chamber was charged with a
solution of arylpyridine (0.25 mmol), I2 (0.50 mmol), and palladium
acetate (0.025 mmol) in acetonitrile (10 mL). A 0.2 M aqueous
solution (10 mL) of sulfuric acid was introduced into the cathodic
chamber. An electric field was applied at 90 °C under a 5 or 10 mA
constant current condition, and the mixture in the anodic chamber was
stirred. After the reaction, the mixture was quenched with an aqueous
solution of K2CO3 and was extracted with EtOAc or Et2O. The
obtained organic portions were washed with saturated Na2S2O3 and
then with brine. The resulting solution was dried over anhydride
Na2SO4 or MgSO4 and concentrated. The iodination product was
isolated by flash column chromatography.
2-(2-Iodo-6-methylphenyl)pyridine (2a). General procedure A
was followed with 42.3 mg (0.250 mmol) of 2-(o-tolyl)pyridine (1a),
prepared according to the procedure reported by Kumada and co-
workers,18 and the reaction was carried out under a 5 mA constant
current condition for 4.5 h. Column chromatography (Chromatorex
NH, hexane and then 30:1 hexane/EtOAc) afforded 65.4 mg of 2a
2-(2-Iodo-5-methylphenyl)-3-methylpyridine (2e). General
procedure A was followed with 45.4 mg (0.248 mmol) of 3-methyl-
2-(3-methylphenyl)pyridine (1e), prepared according to the proce-
dure reported by Queguiner and co-workers,20 and the reaction was
carried out under a 5 mA constant current condition for 3.5 h. Column
chromatography (Chromatorex NH, hexane, then 30:1 hexane/
EtOAc) afforded 57.6 mg of 2e (0.186 mmol, 75% yield) as a
1
colorless oil: H NMR (400 MHz, CDCl3) δ 2.13 (s, 3H), 2.32 (s,
3H), 6.90 (d, J = 7.9 Hz, 1H), 7.08 (s, 1H), 7.20−7.25 (m, 1H), 7.57
(d, J = 7.4 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 8.51 (d, J = 4.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 19.1, 20.9, 93.4, 122.8, 129.9, 130.3,
131.2, 137.7, 138.2, 138.5, 145.0, 146.4, 160.8; IR (neat) 2921 m, 1583
m, 1570 m, 1444 s, 1382 m, 1266 w, 1202 w, 1178 w, 1118 m, 1076 m,
1011 s, 877 m, 805 s, 791 s, 696 w, 632 m, 589 m, 516 w cm−1; MS m/
z (% relative intensity) 310 (6, M+), 309 (39), 206 (17), 183 (14), 182
(100), 181 (18), 180 (16), 167 (63), 91 (18), 90 (12), 84 (12);
HRMS (ESI-TOF) calcd for [M + H]+ (C13H13IN) m/z 310.0093,
found 310.0088.
2-(4-Fluoro-6-iodophenyl)-3-methylpyridine (2f). General
procedure A was followed with 46.9 mg (0.251 mmol) of 2-(4-
fluorophenyl)-3-methylpyridine (1f), prepared according to the
procedure reported by Huff et al.,19 except that 1.00 mmol of I2 was
used. The reaction was carried out under a 5 mA constant current
condition for 10.5 h. Column chromatography (Chromatorex NH,
hexane, then 30:1 hexane/EtOAc) afforded 2f (70% yield) and 1f (4%
yield) as a mixture. Further purification of the mixture by column
chromatography (silica gel 60N, 20:1 CH2Cl2/EtOAc) gave 48.2 mg
of 2f (0.154 mmol, 61% yield) as a colorless oil. 1H NMR
spectroscopic data are in good agreement with those reported in
literature.2d
2-[2-Iodo-4-(trifluoromethyl)phenyl]-3-methylpyridine (2g).
General procedure A was followed with 59.0 mg (0.249 mmol) of 2-
[4-(trifluoromethyl)phenyl]-3-methylpyridine (1g), prepared accord-
ing to the procedure reported by Huff et al.,19 except that 2.00 mmol
of I2 was used. The reaction was carried out under a 10 mA constant
current condition for 11 h. Column chromatography (Chromatorex
NH, hexane, then 30:1 hexane/EtOAc) afforded 2g (82% yield) and
1g (4% yield) as a mixture. Further purification of the mixture by
column chromatography (silica gel 60N, CH2Cl2) gave 63.3 mg of 2g
(0.174 mmol, 70% yield) as a light yellow oil. 1H NMR spectroscopic
data are in good agreement with those reported in literature.2d
2-[2-Iodo-5-(trifluoromethyl)phenyl]-3-methylpyridine (2h).
General procedure A was followed with 59.2 mg (0.250 mmol) of 2-
[3-(trifluoromethyl)phenyl]-3-methylpyridine (1h), prepared accord-
ing to the procedure reported by Huff et al.,19 except that 0.050 mmol
of palladium acetate and 2.50 mmol of I2 were used. The reaction was
carried out under a 10 mA constant current condition for 6 h. Column
chromatography (Chromatorex NH, hexane, then 30:1 hexane/
EtOAc) afforded 57.6 mg of 2h (0.159 mmol, 64% yield) as a
1
(0.222 mmol, 89% yield) as a colorless oil: H NMR (400 MHz,
CDCl3) δ 2.09 (s, 3H), 6.98 (t, J = 7.8 Hz, 1H), 7.19−7.26 (m, 2H),
7.26−7.33 (m, 1H), 7.27−7.83 (m, 2H), 8.73 (d, J = 4.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 21.2, 98.6, 122.4, 124.5, 129.6, 129.9,
136.4, 136.5, 137.7 144.8, 149.5, 161.7; IR (neat) 3048 w, 1589 s, 1563
s, 1476 m, 1443 s, 1279 w, 1174 m, 1146 w, 1085 w, 1025 m, 990 m,
829 w, 769 s, 748 s, 655 m, 620 m, 526 w cm−1; MS m/z (% relative
intensity) 296 (4, M+), 295 (33), 294 (100), 168 (13), 167 (51), 166
(11), 139 (10), 84 (21); HRMS (ESI-TOF) calcd for [M + H]+
(C12H11IN) m/z 295.9936, found 295.9937.
2-[2-Iodo-6-(trifluoromethyl)phenyl]pyridine (2b). General
procedure A was followed with 55.9 mg (0.250 mmol) of 2-[2-
(trifluoromethyl)phenyl]pyridine (1b), prepared according to the
procedure reported by Huff et al.,19 except that 2.00 mmol of I2 was
used. The reaction was carried out under a 10 mA constant current
condition for 11 h. Column chromatography (silica gel 60N, hexane
and then 20:1 hex/EtOAc) afforded 68.8 mg of 2b (0.197 mmol, 79%
yield) as a white solid: mp 113.5−114 °C; 1H NMR (400 MHz,
CDCl3) δ 7.21−7.28 (m, 2H), 7.37 (dd, J = 7.3, 4.9 Hz, 1H), 7.76−
7.82 (2H, m), 8.15 (d, J = 7.8 Hz, 1H), 8.73 (d, J = 4.4 Hz, 1H); 13C
NMR δ 101.4, 123.0 (q, J = 274.7 Hz), 123.2, 124.6, 125.9 (d, J = 4.7
Hz), 129.6, 129.8 (q, J = 30.7 Hz), 136.1, 142.6, 143.4 149.1, 159.2; IR
(KBr) 1578 (m), 1569 (m), 1482 (w), 1442 (w), 1425 (m), 1306 (s),
1204 (m), 1168 (s), 1137 (s) 1057 (m), 995 (m), 802 (m), 795 (m),
784 (m), 747 (m), 683 (s), 668 (m), 626 (w) cm−1; MS m/z (%
relative intensity) 350 (6, M+), 349 (46), 223 (14), 222 (100), 203
(7), 202 (33), 195 (6), 176 (8), 175 (6), 153 (8), 75 (6), 51 (9), 50
(5); HRMS (ESI-TOF) calcd for [M + H]+ (C12H8F3IN) m/z
349.9654, found 349.9650.
2-(2-Iodophenyl)-3-methylpyridine (2c). General procedure A
was followed with 41.8 mg (0.247 mmol) of 3-methyl-2-phenyl-
pyridine (1c), prepared according to the procedure reported by
Kumada and co-workers,18 and the reaction was carried out under a 5
mA constant current condition for 4 h. Column chromatography
(Chromatorex NH, hexane and then 100:1 hexane/EtOAc) afforded
2c (75% yield) and 1c (3% yield) as a mixture. Further purification of
the mixture by column chromatography (silica gel 60N, 20:1 CH2Cl2/
EtOAc) gave 51.1 mg of 2c (0.173 mmol, 70% yield) as a colorless oil.
7721
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The Journal of Organic Chemistry
Note
1
colorless oil: H NMR (400 MHz, CDCl3) δ 2.13 (s, 3H), 7.36−8.28
7.23 (s, 1H), 7.28 (m, J = 7.8 Hz, 2H), 7.35 (d, J = 7.8 Hz, 1H), 8.51
(d, J = 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 18.7, 21.0, 122.0,
126.4, 127.7, 129.1, 129.2, 129.6, 130.5, 131.7, 137.1, 137.5, 137.8,
139.0, 141.0, 146.4, 159.5; IR (KBr) 3017 (w), 2925 (w), 2360 (w),
2332 (w), 1566 (m), 1480 (m), 1445 (s), 1262 (w), 1113 (m), 1070
(m), 829 (m), 796 (s), 775 (s), 706 (s), 633 (w), 584 (w), 513 (w);
MS m/z (% relative intensity) 260 (12, M+), 259 (71), 258 (96), 245
(21), 244 (100), 243 (11), 242 (17), 241 (13), 129 (10), 122 (21),
121 (21); HRMS (ESI-TOF) calcd for [M + H]+ (C19H18N1) m/z
260.1439, found 260.1453.
(m, 2H), 7.52 (s, 1H), 7.63 (d, J = 7.6 Hz, 1H), 8.08 (d, J = 8.4 Hz,
1H), 8.55 (d, J = 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 19.0,
102.2, 123.5, 123.8 (q, J = 272.6 Hz), 126.0, 130.8, 131.1, 131.3, 138.2,
139.7, 146.2, 146.9, 159.6; IR (neat) 3054 (m), 2927 (m), 2359 (w),
1912 (w), 1603 (s), 1449 (s), 1125 (s), 1171 (s), 1051 (m), 903 (s)
851 (m), 798 (s), 719 (s), 630 (s) cm−1; MS m/z (% relative
intensity) 364 (5, M+), 363 (57), 236 (100), 235 (28), 216 (18), 167
(79), 166 (28), 139 (19), 127 (19), 63 (27); HRMS (ESI-TOF) calcd
for [M + H]+ (C13H10F3IN) m/z 363.9810, found 363.9802.
General Procedure B for One-Pot Suzuki−Miyaura Cou-
pling. The electrochemical oxidation was carried out in an H-type
divided cell (anion-exchange membrane) equipped with two platinum
electrodes (1.7 × 1.7 cm2). The anodic chamber was charged with a
solution of arylpyridine (0.25 mmol), I2 (0.50 mmol), and palladium
acetate (0.025 mmol) in acetonitrile (10 mL). A 0.2 M aqueous
solution (10 mL) of sulfuric acid was introduced into the cathodic
chamber. An electric field was applied at 90 °C under a 5 mA constant
current condition, and the mixture in the anodic chamber was stirred.
After the iodination reaction was completed, the electric current was
stopped, and arylboronic acid (0.75 mmol) was added to the anodic
chamber. K2CO3 was added to both anodic (0.75 mmol) and cathodic
(2.5 mmol) chambers. The mixture was heated for an additional 2 h at
90 °C. After the completion of the reaction, the resulting materials in
both chambers were combined and extracted with EtOAc. The
obtained organic portions were washed with brine and dried over
anhydrous Na2SO4 or MgSO4. The solvent was removed, and the
product was isolated by flash column chromatography.
2-(6-Methyl-2-phenylphenyl)pyridine (3a). General procedure
B was followed with 42.7 mg (0.252 mmol) of 2-(o-tolyl)pyridine
(1a). The electrochemical C−H iodination was carried out for 4.5 h.
Column chromatography (Chromatorex NH, hexane and then 30:1
hexane/EtOAc) afforded 3a (84% yield), 1a (6% yield), and 2-(2-
chloro-6-methylphenyl)pyridine (3% yield) as a mixture. Further
purification of the mixture by column chromatography (silica gel 60N,
5:1 hexane(60 °C)/EtOAc) gave 40.1 mg of 3a (0.163 mmol, 65%
yield) as a colorless oil. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
2-[6-Methyl-2-(2-methylphenyl)phenyl]pyridine (3e). Gener-
al procedure B was followed with 42.4 mg (0.251 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (Chromatorex NH, hexane and
then 40:1 hexane/EtOAc) afforded 3e (78% yield), 1a (4% yield), and
2-(2-chloro-6-methylphenyl)pyridine (4%) as a mixture. Further
purification of the mixture by column chromatography (silica gel
60N, 200:1 CH2Cl2/EtOAc and then 100:1 CH2Cl2/EtOAc) gave
1
43.6 mg of 3e (0.168 mmol, 67% yield) as a colorless oil: H NMR
(400 MHz, CDCl3) δ 2.05 (s, 3H), 2.20 (s, 3H), 6.86 (d, J = 7.9 Hz,
1H), 6.94−7.07 (m, 5H), 7.12 (d, J = 7.0 Hz, 1H), 7.28−7.42 (m,
3H), 8.55 (d, J = 4.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.3,
20.5, 121.1, 124.7, 125.1, 126.7, 127.3, 127.6, 129.3, 129.4, 130.4,
135.3, 135.8, 136.5, 139.7, 140.8, 141.0, 148.6, 159.0; MS m/z (%
relative intensity) 260 (9, M+), 259 (57), 258 (100), 245 (13), 244
(61), 243 (8), 242 (13), 241 (11), 215 (8), 165 (9), 129 (12), 128 (7),
122 (18), 121 (17), 80 (18), 79 (20); IR (neat) 3057 (s), 2923 (s),
2736 (w), 1585 (s), 1457 (s), 1276 (m), 1148 (m), 1025 (s), 754 (s)
cm−1; HRMS (ESI-TOF) calcd for [M + H]+ (C19H18N) m/z
260.1439, found 260.1447.
2-[6-Methyl-2-(3-methylphenyl)phenyl]pyridine (3f). General
procedure B was followed with 42.5 mg (0.251 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (Chromatorex NH, hexane and
then 30:1 hexane/EtOAc) afforded 53.0 mg of 3f (0.204 mmol, 81%
yield) as a colorless oil. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
2-[6-Methyl-2-(4-methylphenyl)phenyl]pyridine (3g). Gener-
al procedure B was followed with 41.9 mg (0.248 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 3.5 h. Column chromatography (Chromatorex NH, hexane and
then 30:1 hexane/EtOAc) afforded 49.0 mg of 3g (0.189 mmol, 76%
yield) as a white solid. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
3-Methyl-2-(2-phenylphenyl)pyridine (3b). General procedure
B was followed with 42.7 mg (0.252 mmol) of 3-methyl-2-
phenylpyridine (1c). The electrochemical C−H iodination was carried
out for 4 h. Column chromatography (silica gel 60N, hexane and then
20:1 hexane/EtOAc) afforded 43.3 mg of 3b (0.177 mmol, 70% yield)
1
as a colorless oil. H NMR spectroscopic data are in good agreement
with those reported in literature.21
2-[6-Methyl-2-(4-n-pentylphenyl)phenyl]pyridine (3h). Gen-
eral procedure B was followed with 42.6 mg (0.252 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (Chromatorex NH, hexane and
then 100:1 hexane/EtOAc) afforded 58.5 mg of 3h (0.185 mmol, 74%
yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.87 (t, J = 7.1
Hz, 3H), 1.23−1.31 (m, 4H), 1.54 (tt, J = 7.8, 7.3 Hz, 2H), 2.18 (s,
3H), 2.50 (t, J = 7.8 Hz, 2H), 6.87 (ddd, J = 7.8, 1.2, 1.0 Hz, 1H),
6.92−6.98 (m, 4H), 7.09 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.26−7.29
(m, 2H), 7.35 (d, J = 8.5, 6.6 Hz, 1H), 7.44 (ddd, J = 1.9, 7.6, 7.8 Hz,
1H), 8.63 (ddd, J = 4.9, 1.9, 1.0 Hz, 1H); 13C NMR (100 MHz,
acetone-d6) δ 14.3, 20.6, 23.1, 31.8, 32.1, 35.9, 122.2, 126.3, 128.2,
128.4, 128.6, 129.7, 130.2, 136.3, 137.4, 139.9, 140.7, 141.5, 141.9,
149.6, 160.6; IR (neat) 3127 (w), 3059 (m), 3022 (m), 2957 (s), 2928
(s), 2856 (s), 2733 (w), 1910 (w), 1585 (s), 1562 (s), 1514 (s), 1460
(s), 1423 (s), 1404 (m), 1378 (m), 1283 (w), 1236 (w), 1185 (w),
1147 (m), 1117 (m), 1091 (m), 1053 (w), 1024 (s), 989 (m), 897
(w), 838 (m), 792 (s), 749 (s), 678 (w), 623 (m), 608 (w), 598 (m),
580 (m), 532 (w), 403 (w); MS m/z (% relative intensity) 316 (9,
M+), 315 (46), 314 (100), 258 (16), 257 (12), 256 (10), 244 (6), 242
(8), 241(5); HRMS (ESI-TOF) calcd for [M + H]+ (C23H26N) m/z
316.2065, found 316.2085.
3-Methyl-2-(4-methyl-2-phenylphenyl)pyridine (3c). General
procedure B was followed with 45.9 mg (0.250 mmol) of 3-methyl-2-
(4-methylphenyl)pyridine (1d). The electrochemical C−H iodination
was carried out for 3.5 h. Column chromatography (Chromatorex NH,
hexane and then 30:1 hexane/EtOAc) afforded 54.6 mg of 3c (0.211
1
mmol, 84% yield) as a colorless oil: H NMR (400 MHz, CDCl3) δ
1.75 (s, 3H), 2.45 (s, 3H), 7.06−7.16 (m, 6H), 7.24−7.30 (m, 4H),
8.48 (dd, J = 4.7, 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 18.9,
21.3, 121.9, 126.5, 127.7, 128.1, 129.2, 129.8, 130.4, 131.7, 136.6,
137.4, 137.9, 140.5, 141.2, 146.5, 159.5; IR (neat) 3050 (m), 2922
(m), 2860 (w), 1610 (m), 1583 (m), 1489 (m), 1443 (s), 1267 (w),
1022 (w), 1115 (m), 1066 (w), 1022 (m), 887 (w), 826 (s), 792 (s),
773 (s), 742 (m), 701 (s), 792 (s), 773 (s), 742 (m), 701 (s), 594 (m),
573 (w), 511 (w); MS m/z (% relative intensity) 260 (13, M+), 259
(73), 258 (100), 256 (5), 245 (17), 244 (87), 243 (11), 242 (15), 241
(10), 229 (9), 228 (8), 215 (7), 202 (7), 129 (9), 128 (4), 122 (15),
121 (18), 109 (7); HRMS (ESI-TOF) calcd for [M + H]+ (C19H18N)
m/z 260.1439, found 260.1434.
3-Methyl-2-(5-methyl-2-phenylphenyl)pyridine (3d). General
procedure B was followed with 45.4 mg (0.248 mmol) of 3-methyl-2-
(3-methylphenyl)pyridine (1e). The electrochemical C−H iodination
was carried out for 4 h. Column chromatography (Chromatorex NH,
hexane and then 30:1 hexane/EtOAc) afforded 47.2 mg of 3d (0.182
2-[2-(4-Isopropylphenyl)-6-methylphenyl]pyridine (3i). Gen-
eral procedure B was followed with 42.3 mg (0.250 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (Chromatorex NH, hexane and
1
mmol, 73% yield) as a colorless oil: H NMR (400 MHz, CDCl3) δ
1.73 (s, 3H), 2.43 (s, 3H), 7.07−7.12 (m, 3H), 7.12−7.16 (m, 3H),
7722
dx.doi.org/10.1021/jo3012286 | J. Org. Chem. 2012, 77, 7718−7724

The Journal of Organic Chemistry
Note
then 30:1 hexane/EtOAc) afforded 49.8 mg of 3i (0.173 mmol, 69%
yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 1.17 (d, J = 6.9
Hz, 6H), 2.17 (s, 3H), 2.80 (sep, J = 6.9 Hz, 1H), 6.87 (ddd, J = 7.8,
1.2, 1.0 Hz, 1H), 6.97−6.99 (m, 4H), 7.08 (ddd, J = 7.6, 4.9, 1.2 Hz,
1H), 7.25−7.29 (m, 2H), 7.33 (dd, J = 8.1, 7.1 Hz, 1H), 7.43 (ddd, J =
7.8, 7.6, 1.7 Hz, 1H), 8.63 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 20.4, 23.8, 33.5, 121.2, 125.6, 125.6, 127.6,
127.9, 129.1, 129.5, 135.6, 136.6, 138.9, 139.2, 141.1, 146.7, 148.7,
159.7; IR (neat) 3668 (m), 3128 (m), 3058 (s), 3023 (s), 3001 (s),
2958 (s), 2927 (s), 2869 (s), 2212 (m), 1912 (w), 1733 (m), 1677
(w), 1612 (m), 1586 (s), 1563 (s), 1514 (s), 1459 (s), 1424 (s), 1405
(s), 1382 (m), 1363 (m), 1339 (m), 1265 (m), 1237 (m), 1190 (w),
1171 (m), 1148 (s), 1091 (m), 1053 (s), 1025 (s), 990 (m), 966 (w),
910 (s), 870 (w), 837 (s), 793 (s), 753 (s), 671 (m), 645 (m), 622
(m), 592 (s), 538 (w),525 (w); MS m/z (% relative intensity) 288 (8,
M+), 287 (46), 286 (100), 272 (10), 270 (12), 244 (19), 136 (7), 127
(5); HRMS (ESI-TOF) calcd for [M + H]+ (C21H22N) m/z 288.1752,
found 288.1748.
2-[2-(4-tert-Butylphenyl)-6-methylphenyl]pyridine (3j). Gen-
eral procedure B was followed with 41.9 mg (0.248 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (Chromatorex NH, hexane and
then 20:1 CH2Cl2/EtOAc) afforded 61.3 mg of 3j (0.203 mmol, 82%
yield) as a colorless oil. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
2-[2-(4-Methoxyphenyl)-6-methylphenyl]pyridine (3k). Gen-
eral procedure B was followed with 42.3 mg (0.250 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 3.5 h. Column chromatography (Chromatorex NH, hexane and
then 30:1 hexane/EtOAc) afforded 43.3 mg of 3k (0.157 mmol, 63%
yield) as a colorless oil. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
2-[2-(4-Methoxyphenyl)-4-methylphenyl]-3-methylpyridine
(3l). General procedure B was followed with 46.1 mg (0.252 mmol) of
3-methyl-2-(4-methylphenyl)pyridine (1d). The electrochemical C−H
iodination was carried out for 3.5 h. Column chromatography
(Chromatorex NH, hexane and then 1:1 hexane/EtOAc), followed
by preparative thin-layer chromatography (3:1 hexane/EtOAc),
afforded 48.1 mg of 3l (0.166 mmol, 66% yield) as an yellow oil:
1H NMR (400 MHz, CDCl3) δ 1.74 (s, 3H), 2.44 (s, 3H), 3.74 (s,
3H), 6.69 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 8.7 Hz, 2H), 7.06−7.11 (m,
1H), 7. 20−7.31 (m, 5H), 8.49 (d, J = 4.5 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 18.9, 21.3, 55.1, 113.2, 121.9, 127.7, 129.8, 130.2,
130.2, 131. 7, 133.7, 136.5, 137.4, 137.9, 140.0, 146.5, 158.3, 159.7; IR
(neat) 3650 (w), 3374 (w), 3002 (w), 2835 (s), 2735 (w), 2539 (w),
2208 (w), 2039 (w), 1897 (m), 1770 (w), 1721 (w), 1608 (s), 1582
(s), 1517 (s), 1498 (s), 1441 (s), 1381 (s), 1292 (s), 1247 (s), 1178
(s), 1137 (m), 1113 (s), 1067 (s), 1033 (s), 990 (m), 957 (m), 910
(m), 889 (m), 875 (m), 831 (s), 791 (s), 757 (w), 729 (s), 693 (m),
640 (w), 598 (s), 568 (m), 529 (w); MS m/z (% relative intensity)
290 (10, M+), 289 (48), 288 (28), 275 (20), 274 (100), 246 (6), 245
(8), 231 (15), 230 (8),116 (9); HRMS (ESI-TOF) calcd for [M + H]+
(C20H20NO) m/z 290.1545, found 290.1540.
2-[2-(4-Fluorophenyl)-6-methylphenyl]pyridine (3m). Gener-
al procedure B was followed with 42.3 mg (0.250 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 3.5 h. Column chromatography (Chromatorex NH, hexane and
then 40:1 hexane/EtOAc) afforded 41.6 mg of 3m (0.158 mmol, 63%
yield) as a colorless oil. 1H NMR spectroscopic data are in good
agreement with those reported in literature.15i
2-[6-Methyl-2-{4-(trifluoromethyl)phenyl}phenyl]pyridine
(3n). General procedure B was followed with 42.3 mg (0.250 mmol)
of 2-(o-tolyl)pyridine (1a). The electrochemical C−H iodination was
carried out for 4.5 h. Column chromatography (Chromatorex NH,
hexane and then 30:1 hexane/EtOAc) afforded 3n (70% yield), 1a
(3% yield), and 2-(2-chloro-6-methylphenyl)pyridine (3%) as a
mixture. Further purification of the mixture by column chromatog-
raphy (silica gel 60N, 20:1 CH2Cl2/EtOAc) gave 41.2 mg of 3n (0.131
mmol, 53% yield) as a colorless oil. 1H NMR spectroscopic data are in
good agreement with those reported in literature.15i
2-[2-(4-Bromophenyl)-6-methylphenyl]pyridine (3o). General
procedure B was followed with 42.2 mg (0.249 mmol) of 2-(o-
tolyl)pyridine (1a). The electrochemical C−H iodination was carried
out for 4.5 h. Column chromatography (silica gel 60N, hexane and
then 20:1 hexane/EtOAc) afforded 3o (68%), 1a (1%), and 2-(2-
chloro-6-methylphenyl)pyridine (3%) as a mixture. Further purifica-
tion by GPC gave 46.8 mg of 3o (0.144 mmol, 58% yield) as a
colorless oil. 1H NMR spectroscopic data are in good agreement with
those reported in literature.15i
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C{1H} NMR spectra of new compounds and Figure
S1. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: kakiuchi@chem.keio.ac.jp.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported, in part, by a Grant-in-Aid for
Scientific Research on Priority Areas “Organic Synthesis Based
on Reaction Integration” from the Ministry of Education,
Culture, Sports, Science and Technology, Japan and by Mext-
Supported Program for the Strategic Research Foundation at
Private Universities. We thank Mr. Fumito Saito at Keio
University for experimental assistance. We also thank
Professors Seiji Suga and Koichi Mitsudo at Okayama
University for proofreading of the manuscript.
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The Journal of Organic Chemistry
Note
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3794.
(13) The use of Barluenga’s reagent, IPy2BF4, instead of the
electrochemically generated iodonium ion was not successful for this
palladium-catalyzed C−H iodination. When 0.25 mmol of 1a was
reacted with 2 equiv of IPy2BF4 in 10 mL of acetonitrile in the
presence of 10 mol % of Pd(OAc)2 at 90 °C for 4 h, iodination
product 2a was not observed and 1a was recovered in 89% yield.
(14) Suzuki−Miyaura coupling of certain substrates does not require
stabilizing ligands, which are needed for most of the coupling reactions
proceeding via Pd(0)/Pd(II) catalytic cycles.
(15) Use of arylboron reagents in direct C−H arylation of arenes:
(a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 1698. (b) Kakiuchi, F.; Matsuura, Y.; Kan, S.; Chatani,
N. J. Am. Chem. Soc. 2005, 127, 5936. (c) Ueura, K.; Satoh, T.; Miura,
M. Org. Lett. 2005, 7, 2229. (d) Giri, R.; Maugel, N.; Li, J.-J.; Wang,
D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc.
2007, 129, 3510. (e) Shi, Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.; Cao,
B.; Qin, C.; Wang, Y. Angew. Chem., Int. Ed. 2007, 46, 5554. (f) Vogler,
T.; Studer, A. Org. Lett. 2008, 10, 129. (g) Wang, D.-H.; Mei, T.-S.;
Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 17676. (h) Nishikata, T.; Abela,
A. R.; Huang, S.; Lipshutz, B. H. J. Am. Chem. Soc. 2010, 132, 4978.
(i) Li, H.; Wei, W.; Xu, Y.; Zhang, C.; Wan, X. Chem. Commun. 2011,
47, 1497.
(16) Attempts of the one-pot electrochemical C−H bromination/
Suzuki−Miyaura coupling using the previously reported electro-
chemical C−H bromination method6 and one-pot Suzuki−Miyaura
coupling conditions described here failed to give more than a trace
amount of the arylation product.
(17) Introduction of o-tolyl groups at ortho positions of arylpyridines
by direct C−H arylation has been reported using reagents other than
arylboron reagents: (a) Arockiam, P.; Poirier, V.; Fischmeister, C.;
Bruneau, C.; Dixneuf, P. H. Green. Chem. 2009, 11, 1871. (b) Li, B.;
Wu, Z.-H.; Gu, Y.-F.; Sun, C.-L.; Wang, B.-Q.; Shi, Z. Angew. Chem.,
Int. Ed. 2011, 50, 1109.
(18) Kumada, M.; Tamao, K.; Sumitani, K. Org. Synth. 1978, 58, 127.
(19) Huff, B. E.; Koenig, T. M.; Mitchell, D.; Staszak, M. A. Org.
Synth. 1998, 75, 53.
(20) Bonnet, V.; Mongin, F.; Trecourt, F.; Queguiner, G.; Knochel,
P. Tetrahedron 2002, 58, 4429.
(21) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am.
Chem. Soc. 2005, 127, 7330.
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