Palladium-catalyzed cyanation of aryl halides with CuSCN

Article abstract of DOI:10.1021/jo3025829

A palladium-catalyzed cyanation of aryl halides and borons has been developed by employing cuprous thiocyanate as a safe cyanide source. This protocol avoids the use of a highly toxic cyanide source, providing aromatic nitriles in moderate to good yields with good functional tolerance.

Full text of DOI:10.1021/jo3025829

Note
pubs.acs.org/joc
Palladium-Catalyzed Cyanation of Aryl Halides with CuSCN
‡
†
‡
,†
Guo-Ying Zhang, Jin-Tao Yu, Mao-Lin Hu, and Jiang Cheng*
†
School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
‡
*
S Supporting Information
ABSTRACT: A palladium-catalyzed cyanation of aryl halides
and borons has been developed by employing cuprous
thiocyanate as a safe cyanide source. This protocol avoids
the use of a highly toxic cyanide source, providing aromatic
nitriles in moderate to good yields with good functional
tolerance.
itriles have occupied pivotal positions in organic
Scheme 1. Design Plan
N
chemistry due to facile transformations of nitriles to
aldehydes, amines, amidines, tetrazoles, amides, and their
1
carboxyl derivatives. Moreover, they are also versatile building
blocks in the synthesis of natural products, pharmaceuticals,
2
materials, agricultural chemicals, and dyes. Recently, the
transition-metal-catalyzed cyanation of aryl halides, borons,
mesylates, and arene C−H bonds has become a common and
powerful transformation in organic synthesis. With respect to
3
−11
the cyanide sources, MCN (M = Na, K, Cu, Zn, TMS),
1
2,13
14
15−17
18
acetone cyanohydrin,
BnSCN, acetonitrile,
DDQ,
1
9
N-cyano-N-phenyl-p-toluenesulfonamide, ethyl cyanoace-
Importantly, CuSCN is low toxicity to humans and the
2
0
21−24
39
tate, and K [Fe(CN) ] and K [Fe(CN) ]
have been
environment. Herein, we report our preliminary study in the
3
6
4
6
successfully applied. However, except for the aforementioned
last five types of cyanide sources, the toxicity of the cyanide
source would greatly limit the utility of such transformations,
especially in large scale. To circumvent this drawback, much
attention has been paid to the development of safe cyanide
cyanation reaction of aryl halides with CuSCN as a safe and
new cyanide source.
Obviously, for the former route, an additional reductant
might be needed to regenerate Pd(0) species in the catalytic
cycle. With these considerations in mind, we initially conducted
the reaction of p-iodoanisole 1b (1.4 equiv) and CuSCN with
sodium formate (3 equiv) as the reductant. The copper(I)
could promote the cyanation reaction to some extent since the
desired product was obtained in 21% yield with the
combination of 1b, CuSCN, formic acid, and sodium formate
2
5
sources for the cyanation reaction. Recently, Chang
pioneered a combination of ammonia and DMF as safe cyanide
2
6,27
sources in cyanation of 2-aryl pyridine C−H bonds.
Theses
reports presented a new concept that the cyano group could be
generated from DMF and ammonium safely and conveniently
in cyanation reactions. Subsequently, we found that the
combination of ammonium and DMSO or DMF enabled
in DMSO/H O (entry 1, Table 1). To our delight, the reaction
2
efficiency was improved by using Pd(OAc) (entry 2, Table 1).
2
2
8
29
Some palladium sources were tested. Gratifyingly, p-anisonitrile
cyanation of an indole C−H bond or aryl halide. Shortly
was isolated in 83% yield when PdCl (dppe) was employed as
afterward, Jiao reported the direct cyanation of an indole C−H
bond using DMF. Togo et al. also demonstrated conversion
of aromatic bromides and aromatics into aromatic nitriles via
2
30
the catalyst (entry 6, Table 1). Under N , a comparable yield
2
was obtained, indicating the O should not take part in the
2
31−35
reaction. Further study revealed that the acid was crucial for this
transformation. HCOOH gave the best outcome and other
aryllithiums and their DMF adducts.
Nevertheless, the
aforementioned procedures suffered from limited substrate
scope or harsh reaction conditions. Thus, the development of a
new procedure with broad substrate scope would dramatically
improve the practicality of safe cyanation reactions.
acids, such as CF COOH, CH COOH, and PhCOOH,
3
3
resulted in low yields (entries 11−13, Table 1). The acid was
believed to accelerate the reaction since in the absence of acid,
the reaction became sluggish. However, with prolonged
reaction time, the cyanation product was still isolated in 81%
yield (entry 7, Table 1). The sodium formate played an
3
6,37
38
Larock
and Lu have demonstrated that the nitrile
group could produce imines via carbopalladation and
subsequent protonation. We envisaged CuSCN would possess
the potential similar chemistry leading to the formation of
benzothioamide as a precursor to nitriles (Scheme 1). Thus, it
may provide a new strategy for aryl nitrile synthesis.
Received: November 27, 2012
Published: February 7, 2013
©
2013 American Chemical Society
2710
dx.doi.org/10.1021/jo3025829 | J. Org. Chem. 2013, 78, 2710−2714

The Journal of Organic Chemistry
Note
a
Table 1. Screening Conditions
entry
Pd source
acid
additive
solvent
yield (%)
1
2
3
4
5
6
7
8
9
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
DMSO/H O
21
48
53
38
46
2
Pd(OAc)2
DMSO/H O
2
PdCl (PPh )
DMSO/H O
2
3
2
2
PdCl2
DMSO/H O
2
Pd(dba)2
DMSO/H O
2
b
PdCl (dppe)
DMSO/H O
83 (80)
2
2
c
d
PdCl (dppe)
DMSO/H O
36 (41) (81)
2
2
PdCl (dppe)
DMSO/H O
<5
<5
<5
52
56
41
28
40
57
49
2
2
HCOONa
DMSO/H O
2
10
11
12
13
14
15
16
17
18
19
20
21
DMSO/H O
2
PdCl (dppe)
CF COOH
3
HCOONa
HCOONa
HCOONa
DMSO/H O
2
2
PdCl (dppe)
CH COOH
DMSO/H O
2
3
2
PdCl (dppe)
PhCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
HCOOH
DMSO/H O
2
2
PdCl (dppe)
DMSO/H O
2
2
PdCl (dppe)
PhCOONa
DMSO/H O
2
2
PdCl (dppe)
CH COOK
DMSO/H O
2
3
2
PdCl (dppe)
Na C O
DMSO/H O
2
2
2
4
2
e
PdCl (dppe)
HCOONa
HCOONa
HCOONa
HCOONa
DMSO/H O
67
2
2
PdCl (dppe)
DMSO
76
0
2
PdCl (dppe)
toluene/H O
2
2
PdCh(dppe)
DMF/H O
61
2
a
Reaction conditions: p-iodoanisole 1b (0.7 mmol), CuSCN (0.5 mmol), [Pd] (1 mol %), acid (10 mol %), additive (3.0 equiv), under air, solvent/
b
c
d
e
H O = 8:1 (3 mL), 100 °C, 36 h. N . 48 h. 48 h, DMSO = 3 mL. DMSO/H O = 6/1 (3 mL).
2
2
2
important role on this transformation since removing or
replacing sodium formate with other carboxylates dramatically
decreased the reaction efficiency. Meanwhile, reaction in other
solvents, such as toluene/H O and DMF/H O resulted in
alkyl iodides failed to cyanate under the standard reaction
conditions.
To extend the scope of our catalytic system, we also tested
aryl bromides and borons under the standard procedure (Table
2). The nitriles were obtained in moderate yields. Aryl chloride
did not work under this procedure. Since the cyanation of
boronic acid is triggered by the transmetalation of Pd(II) with
arylboronic acid, we reasoned the cyanation yield would
improve in the absence of HCOONa. However, a serious
homocoupling of arylboronic acid resulted in low yield in this
cyanation reaction.
Other substrates containing the XCN (X = O, S) moiety
were tested in the newly developed cyanation procedure
(Scheme 2). However, in the absence of copper, no reaction
took place for KSCN under the indicated conditions.
Fortunately, in the presence of 1 equiv of CuI, KSCN ran
smoothly to provide the cyanation products in moderate yield.
Moreover, KOCN was a potential partner in such trans-
formation, albeit the cyanated products was isolated in low
yield. Notably, methyl thiocyanate and 1-methyl-4-thiocyana-
tobenzene also provided the cyanation products in good yields,
respectively.
Next, we conducted the reaction of p-iodoanisole and
CuSCN on a 10 mmol scale with elongated time, and
anisonitrile was isolated in an acceptable 73% (0.97 g) yield,
which greatly increased the practicality of this palladium-
catalyzed cyanation reaction.
4-Methylbenzothioamide was subjected to the standard
procedure, and the cyanation product was isolated in 51%
yield in 20 h, while no cyanation product was detected for 4-
methoxybenzamide in 36 h. Moreover, during the reaction of
KOCN and p-iodoanisole, p-methoxybenzamide was detected
as byproduct (Scheme 3). These results were all consistent with
the possibility of a carbopalladation step and p-methylbenzo-
2
2
lower yield or no reaction (entries 20 and 21, Table 1). The
ratio of DMSO/H O had some effect on the reaction. For
2
example, the yield dropped to 67% in DMSO/H O = 6:1
2
(
entry 18, Table 1). Finally, we identified the optimal reaction
medium as an 8:1 DMSO/H O mixture. The dehalogenation
2
byproduct was detected by GC−MS, but the thiocyanate
41
coupled product or the diaryl sulfide was not found. Thus,
excess aryl iodides were required to fulfill the reaction.
After the establishment of optimized reaction conditions, we
extended this new protocol to a range of aryl iodides. As
illustrated in Figure 1, the procedure tolerated well some
functional groups, such as methoxy, benzyloxy, acetyl, free
phenolic hydroxyl, free amino, and acetamido, with good yields.
The electronic nature of aryl iodides had some effect on the
reaction. Generally, the aryl iodides with electron-withdrawing
groups gave slightly lower yields than those electron-donating
analogues (2a−2i vs 2p−2s, Figure 1). This was consistent
with Larock’s procedure on the palladium-catalyzed cyclization
3
6
of ω-(2-iodoaryl)alkanenitriles. The low yield in the
cyanation of the electron-poor aryl iodides may be at least
partly due to the reduced nucleophilicity of the arylpalladium
intermediate involved in the presumed carbopalladation of CN
moiety in thiocyanate (vide infra). Importantly, the ortho group
in aryl iodides hardly had an effect on the reaction efficiency
(
2b,2c vs 2d−2f, Figure 1). Notably, the mono-, di-, and
trimethoxy aryl iodides all worked well with excellent yields
(
2b−2g, Figure 1). Fortunately, free phenolic hydroxyl and
amino groups were tolerated well in the standard procedure
without any protection. However, β-iodo naphthalene afforded
the cyanation products in moderate yields. Disappointingly,
2
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The Journal of Organic Chemistry
Note
Scheme 2. Pd-Catalyzed Cyanation of 1b with Other
a
Cyanide Sources
a
Reaction conditions: 1b (0.7 mmol), MCN (0.5 mmol),
PdCl (dppe) (1 mol %), CuI (0.5 mmol), HCOOH (10 mol %),
2
HCOONa (3.0 equiv), under air, DMSO (3 mL), 100 °C, 36 h.
a
Scheme 3. Pd-Catalyzed Cyanation of 3a and 3b
a
Reaction conditions were the same as in Scheme 2.
A tentative mechanism is illustrated in Scheme 4. In step i,
the oxidative addition of ArI to Pd(0), which derives from the
Scheme 4. Plausible Mechanism
Figure 1. Palladium-catalyzed cyanation of aryl iodides. Reaction
conditions: 1a−1u (0.7 mmol), CuSCN (0.5 mmol), PdCl (dppe) (1
2
mol %), HCOOH (10 mol %), HCOONa (3.0 equiv), under air,
b
DMSO/H O = 8:1 (3 mL), 100 °C, 36 h. Notes: No HCOOH, 48 h,
DMSO = 3 mL. p-Iodophenyl acetate.
2
c
Table 2. Palladium-Catalyzed Cyanation of Aryl Bromides
a
and Borons
41−43
reduction of Pd(II) with HCOONa,
forms ArPdI. Step ii
involves the carbopalladation of ArPdI to form Pd(II) species
A. Wang reported palladium-catalyzed cyanide metathesis of
benzyl cyanide, where the carbopalladation of the cyano moiety
44
was the key step in the catalytic cycle. Then, in step iii, the
hydrolysis of intermediate A by acid releases the Pd(II) species
B, along with benzothioamide. Benzothioamide converts to the
4
5,46
aryl nitrile via the loss of H S.
In step iv, the reaction of
2
sodium formate with species B releases 1 equiv of CO and
2
formic acid, followed by the reductive elimination to regenerate
Pd(0) species. Thus, a catalytic amount of formic acid is
sufficient to promote the reaction. Notably, in the presence of
palladium, 21% of cyanation product was isolated. This result
implied Cu(I) could promote the cyanation reaction to some
extent. In this case, aryl cuprate species may be formed as the
a
Reaction conditions were the same as in Figure 1.
thioamide as the potential intermediate. The low yield of
KOCN may be due to the low reactivity of benzamide to nitrile
under the standard procedure.
2
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The Journal of Organic Chemistry
Note
4
7
29
intermediate in an Ullmann reaction, and then the aryl
cuprate species undergoes a similar process as the ArPd(II)
does in steps ii−iv in Scheme 4 to yield the cyanation product.
Meanwhile, an alternative pathway may involve the following
steps: (1) the formation of PhSCN via the palladium-catalyzed
reaction of aryl iodides with CuSCN; (2) cleavage of the S-CN
2,3,4-Trimethoxybenzonitrile (2f). Colorless solid (71.4 mg, 74%
1
yield); H NMR (CDCl , 500 MHz) δ 7.20 (d, J = 8.5 Hz, 1H), 6.62
d, J = 9.0 Hz, 1H), 3.98 (s, 3H), 3.84 (s, 3H), 3.79 (s, 3H); C NMR
CDCl , 125 MHz) δ 157.9, 155.7, 141.7, 128.7, 116.5, 107.4, 99.0,
3
1
3
(
(
6
3
1.7, 61.0, 56.2.
,4,6-Trimethoxybenzonitrile (2g). Colorless solid (77.2 mg, 80%
50
2
1
yield); H NMR (CDCl , 500 MHz) δ 6.05 (s, 2H), 3.87 (s, 6H), 3.84
s, 3H); C NMR (CDCl , 125 MHz) δ 165.3, 163.7, 114.6, 90.3,
47
3
bond; (3) the palladium-catalyzed cyanation. However, in this
pathway, 2 equiv of aryl iodides were required to form the
cyanation product. The fact of high yields for some substrates
in Figure 1 strongly argues against this pathway. However, the
detailed mechanism is unclear at the current stage.
In conclusion, we have developed an unprecedented and
simple procedure for the cyanation of aryl halides employing
CuSCN as an inexpensive and nontoxic cyanide source. The
procedure represents good functional tolerance as well as the
capability for 10 mmol scale preparation. As such, it represents
a novel and safe method to access aromatic nitriles.
13
(
8
3
4.0, 56.0, 55.6.
1,1′-Biphenyl)-4-carbonitrile (2h). Colorless solid (75.2 mg,
2
9
(
1
84% yield); H NMR (CDCl , 500 MHz) δ 7.74−7.68 (m, 4H), 7.59
3
1
3
(d, J = 7.5 Hz, 2H), 7.51−7.48 (m, 2H), 7.44−7.42 (m, 1H);
NMR (CDCl , 125 MHz) δ 145.6, 139.1, 132.5, 129.1, 128.6, 127.7,
27.2, 118.9, 110.9.
-(Benzyloxy)benzonitrile (2i). Colorless solid (79.4 mg, 76%
C
3
1
29
4
1
yield); H NMR (CDCl , 500 MHz) δ 7.60−7.58 (m, 2H), 7.92−7.88
3
13
(
m, 5H), 7.02−7.01 (m, 2H), 5.12 (s, 2H); C NMR (CDCl , 125
3
MHz) δ 161.9, 135.6, 133.9, 128.7, 128.3, 127.4, 119.1, 115.5, 104.1,
7
0.2.
-Chlorobenzonitrile (2j). Colorless solid (30.1 mg, 44% yield);
49
4
1
EXPERIMENTAL SECTION
H NMR (CDCl , 500 MHz) δ 7.60 (d, J = 8.0 Hz, 2H), 7.47 (d, J =
3
■
8
.0 Hz, 2H); 13C NMR (CDCl , 125 MHz) δ 139.5, 133.3, 129.7,
3
General Information. Chemicals were either purchased or
purified by standard techniques. H NMR and C NMR spectra
were measured on a 500 MHz spectrometer ( H 500 MHz, C 125
MHz), using CDCl as the solvent at room temperature. Chemical
shifts (in ppm) were referenced to tetramethylsilane (δ = 0 ppm) or
.26 ppm in CDCl as an internal standard. C NMR spectra were
obtained by using the same NMR spectrometers and were calibrated
with CDCl (δ = 77.00 ppm). Chemical shifts are given in δ relative to
TMS, the coupling constants J are given in hertz. Column
chromatography was performed using EM silica gel 60 (300−400
mesh).
General Procedure for the Reaction of Aryl Iodides,
Bromines, and Borons with CuSCN Leading to Nitriles. Under
air, a Schlenk tube was charged with CuSCN (60.8 mg, 0.5 mmol), aryl
iodides (0.7 mmol, 1.25 equiv), PdCl (dppe) (2.9 mg, 1 mol %),
HCOONa (102.0 mg, 3.0 equiv), HCOOH (2.0 μL, 10 mol %), and
DMSO/H O = 8:1 (3.0 mL). The mixture was stirred at 100 °C (oil
bath temperature) for 36 h, or until complete consumption of starting
material as monitored by TLC or GC−MS analysis. The color of the
reaction solution started as muddy and ended as dark after the reaction
was finished. The reaction mixture was allowed to cool to room
temperature, poured into 20 mL of brine, and extracted with EtOAc (4
5 mL). The combined organic layers were washed with water and
dried over MgSO , and the solvents were removed under vacuum. The
residue was purified by flash column chromatography (petroleum
ether/ethyl acetate) to afford the desired product 2a--2u.
1
13
117.9, 110.7.
49
1
13
4-Bromobenzonitrile (2k). Colorless solid (29.8 mg, 33% yield);
1
H NMR (CDCl , 500 MHz) δ 7.64 (d, J = 8.5 Hz, 2H), 7.53 (d, J =
3
3
8
1
.5 Hz, 2H); 13C NMR (CDCl , 125 MHz) δ 133.3, 132.6, 127.9,
3
1
3
18.0, 111.2.
4
7
3
29
-Hydroxybenzonitrile (2l). Colorless solid (45.2 mg, 76% yield);
H NMR (CDCl , 500 MHz) δ 7.55 (d, J = 8.5 Hz, 2H), 6.94 (d, J =
9.0 Hz, 2H), 6.77 (br, 1H); C NMR (CDCl
134.3, 119.2, 116.4, 103.0.
4-Aminobenzonitrile (2m). Colorless solid (40.1 mg, 68% yield);
H NMR (CDCl , 500 MHz) δ 7.39 (d, J = 8.0 Hz, 2H), 6.63 (d, J =
.1 Hz, 2H), 4.23 (s, 2H); C NMR (CDCl , 125 MHz) δ 150.5,
1
3
3
13
, 125 MHz) δ 160.2,
3
49
1
3
13
8
1
3
33.7, 120.1, 114.3, 99.9.
49
2
N-(4-Cyanophenyl)acetamide (2n). Colorless solid (56.0 mg,
0% yield); H NMR (DMSO-d , 500 MHz) δ 10.4 (s, 1H), 7.72 (s,
4H), 2.07(s, 3H); C NMR (DMSO-d , 125 MHz) δ 169.4, 143.3,
1
7
6
13
2
6
1
33.2, 119.1, 119.0, 104.7, 24.0.
-(Dibutylamino)benzonitrile (2o). Colorless solid (56.3 mg,
29
4
1
4
6
1
9% yield); H NMR (CDCl , 500 MHz) δ 7.40 (d, J = 9.0 Hz, 2H),
3
.56 (d, J = 9.0 Hz, 2H), 3.29 (t, J = 8.0 Hz, 4H). 1.59−1.52 (m, 4H),
13
.39−1.31 (m, 4H), 0.96 (t, J = 7.5 Hz, 6H); C NMR (CDCl , 125
3
×
MHz) δ 150.6, 133.4, 120.8, 111.0, 96.1, 50.6, 29.0, 20.1, 13.8.
29
4
4
-Acetylbenzonitrile (2p). Colorless solid (44.9 mg, 62% yield);
H NMR (CDCl , 500 MHz) δ 8.04 (d, J = 8.5 Hz, 2H), 7.78 (d, J =
8.5 Hz, 2H), 2.65 (s, 3H); C NMR (CDCl
39.9, 132.5, 128.7, 117.9, 116.4, 26.7.
4-Formylbenzonitrile (2q). Colorless solid (28.2 mg, 43% yield);
H NMR (CDCl , 500 MHz) δ 10.1 (s, 1H), 8.0 (d, J = 8.0 Hz, 2H),
7.85 (d, J = 8.0 Hz, 2H); C NMR (CDCl , 125 MHz) δ 190.6, 138.8,
1
3
13
4
9
1
3
, 125 MHz) δ 196.5,
4
-Methylbenzonitrile (2a). Colorless oil (41.6 mg, 71% yield); H
NMR (CDCl , 500 MHz): δ 7.47 (d, J = 7.5 Hz, 2H), 7.20 (d, J = 8.0
Hz, 2H), 2.35 (s, 3H); C NMR (CDCl , 125 MHz) δ 143.7, 132.0,
1
3
6
13
3
1
3
1
29.8, 119.1, 109.3, 21.8.
13
4
9
4
-Methoxybenzonitrile (2b). Colorless solid (55.2 mg, 83%
yield); H NMR (CDCl , 500 MHz) δ 7.58 (d, J = 8.0 Hz, 2H), 6.95
d, J = 8.5 Hz, 2H), 3.86 (s, 3H); C NMR (CDCl , 125 MHz) δ
3
1
132.9, 129.9, 117.7, 117.6.
3
29
13
Methyl-2-cyanobenzoate (2r). Colorless solid (46.7 mg, 58%
(
1
3
1
yield); H NMR (CDCl , 500 MHz) δ 8.14−8.13 (m, 1H), 7.81−7.80
62.8, 134.0, 119.2, 114.7, 103.9, 55.5.
3
13
5
0
(
m, 1H), 7.70−7.64 (m, 2H), 4.00 (s, 3H); C NMR (CDCl , 125
3
,4-Dimethoxybenzonitrile (2c). Colorless solid (63.6 mg, 78%
yield); H NMR (CDCl , 500 MHz) δ 7.28 (d, J = 8.0 Hz, 1H), 6.90
s, 1H), 6.90 (d, J = 8.5 Hz, 1H), 3.93 (s, 3H), 3.90 (s, 3H); C NMR
CDCl , 125 MHz) δ 152.9, 149.2, 126.5, 119.2, 114.0, 111.2, 103.9,
3
1
MHz) δ 164.4, 134.7, 132.6, 132.4, 132.3, 131.1, 117.4, 112.9, 52.8.
3
29
1
1
3
4
-Nitrobenzonitrile (2s). Yellow solid (34.8 mg, 47% yield); H
(
(
5
NMR (CDCl , 500 MHz) δ 8.36 (d, J = 8.5 Hz, 2H), 7.89 (d, J = 8.5
3
3
Hz, 2H); 13C NMR (CDCl , 125 MHz) δ 150.0, 133.4, 124.3, 118.3,
6.1, 56.0.
3
5
0
2
,4-Dimethoxybenzonitrile (2d). Colorless solid (61.9 mg, 76%
yield); H NMR (CDCl , 500 MHz) δ 7.44 (d, J = 9.0 Hz, 1H), 6.50
d, J = 8.5 Hz, 1H), 6.44 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H); C NMR
CDCl , 125 MHz) δ 164.6, 162.8, 134.8, 116.9, 105.7, 98.4, 93.8,
116.8.
29
1
1
2-Naphthonitrile (2t). Colorless solid (39.0 mg, 51% yield); H
NMR (CDCl , 500 MHz) δ 8.23 (s, 1H), 7.92−7.88 (m, 3H), 7.67−
7.59 (m, 3H); C NMR (CDCl , 125 MHz) δ 134.6, 134.1, 132.2,
3
13
(
(
3
13
3
3
5
5.9, 55.6.
129.2, 129.0, 128.4, 128.0, 127.6, 126.3, 119.2, 109.4.
2
9
10
2
,4,5-Trimethoxybenzonitrile (2e). Colorless solid (65.6 mg, 68%
yield); H NMR (CDCl , 500 MHz) δ 6.92 (s, 1H), 6.48 (s, 1H), 3.92
s, 3H), 3.89 (s, 3H), 3.81 (s, 3H); C NMR (CDCl , 125 MHz) δ
57.6, 154.1, 143.0, 116.9, 114.7, 96.4, 91.4, 56.5, 56.1.
2-(Pyridin-2-yl)benzonitrile (2u). Colorless solid (65.7 mg, 73%
1
1
yield); H NMR (CDCl
, 500 MHz) δ 8.76 (d, J = 4.5 Hz, 1H), 7.85−
3
3
1
3
(
1
7.83 (m, 2H), 7.78 (t, J = 7.5 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.50 (t,
3
13
J = 8.0 Hz, 1H), 7.37−7.35 (m, 1H); C NMR (CDCl , 125 MHz) δ
3
2
713
dx.doi.org/10.1021/jo3025829 | J. Org. Chem. 2013, 78, 2710−2714

The Journal of Organic Chemistry
Note
1
1
55.0, 149.7, 143.1, 137.0, 134.0, 132.8, 129.9, 128.8, 123.3, 123.2,
18.6, 111.0.
(27) Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc. 2012, 134,
2528.
(
28) Ren, X.; Chen, J.; Chen, F.; Cheng, J. Chem. Commun. 2011, 47,
725.
29) Zhang, G.; Ren, X.; Chen, J.; Hu, M.; Cheng, J. Org. Lett. 2011,
3, 5004.
6
ASSOCIATED CONTENT
■
(
*
S
Supporting Information
1
1
13
H and C NMR spectra of compounds 2a−2u. This material
(30) Ding, S.; Jiao, N. J. Am. Chem. Soc. 2011, 133, 12374.
(31) Ushijima, S.; Moriyama, K.; Togo, H. Tetrahedron 2011, 67,
58.
is available free of charge via the Internet at http://pubs.acs.org.
9
(
32) Ishii, G.; Moriyama, K.; Togo, H. Tetrahedron Lett. 2011, 52,
AUTHOR INFORMATION
■
*
2
404.
Corresponding Author
E-mail: jiangcheng@cczu.edu.cn.
(33) Ushijima, S.; Togo, H. Synlett 2010, 1562.
(34) Ushijima, S.; Togo, H. Synlett 2010, 1067.
(35) Ushijima, S.; Moriyama, K.; Togo, H. Tetrahedron 2012, 68,
Notes
4
588.
The authors declare no competing financial interest.
(36) Zhou, C.; Larock, R. C. J. Am. Chem. Soc. 2004, 126, 2302.
(37) Zhou, C.; Larock, R. C. J. Org. Chem. 2006, 71, 3551.
ACKNOWLEDGMENTS
(38) Zhao, L.; Lu, X. Angew. Chem., Int. Ed. 2002, 41, 4343.
■
(39) O’Regan, B.; Schwartz, D. T. Chem. Mater. 1995, 7, 1349.
We thank the National Natural Science Foundation of China
nos. 21272028 and 21202013), the Natural Science
Foundation of Zhejiang Province (no. R4110294), and the
Priority Academic Program Development of Jiangsu Higher
Education Institutions for financial support.
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