Copper-catalyzed cyanation of aryl iodides with malononitrile: An unusual cyano group transfer process from C(sp3) to C(sp2)

Article abstract of DOI:10.1002/adsc.201100836

An unusual copper-catalyzed cyanation of aryl iodides to form aryl nitriles by cyano group transfer from C(sp³) to C(sp²) carbon atoms is reported and proceeds to give yields of up to 86%. Copyright

Full text of DOI:10.1002/adsc.201100836

COMMUNICATIONS
DOI: 10.1002/adsc.201100836
Copper-Catalyzed Cyanation of Aryl Iodides with Malononitrile:
3
2
An Unusual Cyano Group Transfer Process from C
A
H
U
G
E
N
N
(sp ) to C
ACHTUNGTRENNUNG
a
a
a
b
a,b,
Zhaoqiong Jiang, Qing Huang, Si Chen, Lasheng Long, and Xiangge Zhou *
a
Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, Peopleꢀs Republic of
China
Fax : (+86)-28-8541-2904; e-mail: zhouxiangge@scu.edu.cn
State Key Laboratory of Physical Chemistry of Solid Surface, Xiamen University, Xiamen 361005, Peopleꢀs Republic of
b
China
Received: October 26, 2011; Revised: November 18, 2011; Published online: February 23, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100836.
Abstract: An unusual copper-catalyzed cyanation of
nickel bisphosphine complexes in the presence of zinc
metal powder to obtain ArCN compounds was report-
ed by Cheng and co-workers. However, substituents
aryl iodides to form aryl nitriles by cyano group
3
2
[13]
transfer from C
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(sp ) to C
A
H
U
G
R
N
U
G
ported and proceeds to give yields of up to 86%.
at the ortho position of the aryl halides were needed
in these cases, and a stoichiometric amount of zinc
metal was consumed during catalysis.
Keywords: catalysis; CÀC activation; copper; cyano
group transfer
It was reported by Suzuki and Miura et al. that cop-
per(I) iodide could catalyze couplings of aryl iodides
with malononitrile under a nitrogen atmosphere to
provid the corresponding C-arylation products
[
14]
(
Scheme 1, A). Very recently, Fu et al. used CuI/l-
Activation and transformation of CÀC bonds is one proline as catalyst to give aromatic carboxylic acids in
[
15]
of the key processes in organic chemistry, which has the air (Scheme 1, B). We herein disclose the cop-
[
1]
fascinated chemists for a long time. CÀCN bonds, per(II)-catalyzed cyanation of aryl iodides with malo-
3
which are common and abundant in many organic nonitrile through cyano group transfer from C
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(sp ) to
2
molecules, can be cleavable upon treatment with cer-
C AHCTUNGTERNNUNG( sp ) (Scheme 1, C).
[
2]
tain transition metal complexes, due presumably to
a kinetically favorable interaction of the cyano group
1
2
with the transition metal through h - or h -coordina-
tion and the resultant highly stable metalÀCN bond
[
3]
being a thermodynamic driving force. For example,
transition metals such as Pt, Pd, Ni, Rh, Co, Fe, Ru,
Cu, and Ag have been reported to form metal cyanide
[
2,4,5]
complexes by the cleavage of CÀCN bonds.
Fur-
thermore, in some cases, the cyano group is used as
[6]
a leaving group. The cleavage of CÀCN bonds and
addition across alkynes and alkenes was reported by
[
7]
Nozaki and co-workers as early as 1971, and devel-
[
3,8]
oped well by Nakao, Hiyama and co-workers.
On the other hand, aryl nitriles are of substantial
Scheme 1. Copper-catalyzed reactions of aryl iodides with
interests as integral ingredients of dyes, herbicides, malononitrile.
natural products, agrochemicals, and pharmaceuti-
[9]
cals. One of the most convenient synthetic methods
is the reaction of aryl halides with cyanide sources in-
Initially, we chose p-iodotoluene as model substrate
[
10]
cluding KCN, K [Fe(CN) ], TMSCN, or acetone cy- for the optimization of the reaction conditions. The
4
6
[11]
anohydrin, based on the transition metal-mediated standardized protocol was carried out by using p-io-
[12]
protocol. In addition, catalytic cyano group transfer dotoluene (1 equiv.), malononitrile (2 equiv.), base
from acetonitrile to aryl halides by palladium and (2 equiv.), Cu source (10 mol%) and ligand
Adv. Synth. Catal. 2012, 354, 589 – 592
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
589

Zhaoqiong Jiang et al.
COMMUNICATIONS
(
20 mol%) in DMF at 1108C for 18 h. As shown in other solvents were tested, 1,4-dioxane and toluene
Table 1, among the bases examined, t-BuONa gave resulted in traces of product and pyridine resulted in
the best yield of around 43% (Table 1, entries 1–7). a low yield of 26%. In addition, the effects of reaction
Different copper sources were then examined, and temperatures of 908C, 1108C, 1208C, 1308C were
Cu ACHTUNGTRENNUNG( OAc) resulted in the best yield of 54% (Table 1, tested, and 1208C was proved to be suitable for the
2
entries 8–15). Control experiments indicated the ne- reaction giving a 58% yield (Table 1, entry 21). Fur-
cessity of both metal and ligand, there was only trace thermore, several additives including LiCl, KF, KI
of product detected in the absence of either of them and CaF , and KF were tested, and KF was found to
2
(
Table 1, entries 16 and 20).
Among the ligands used, 1,10-phenanthroline was (Table 1, entries 22–25).
more beneficial to the catalysis than the others Next, the scope of this catalytic system was extend-
Table 1, entries 15, 17–19). And only traces of arylat- ed to various aryl iodides under the optimized reac-
ed malononitrile by-product are observed. Some tion conditions: aryl iodides (0.5 mmol), malononitrile
1 mmol), t-BuONa (1 mmol), KF (1 mmol),
Cu(OAc) (0.05 mmol) and 1,10-phenanthroline
0.1 mmol) in DMF (2 mL) at 1208C for 18 h. The re-
be beneficial to the catalysis with yields of up to 75%
(
(
AHCTUNGTRENNUNG
2
Table 1. Screening of reaction conditions for the copper-cat-
alyzed cyanation of p-iodotoluene with malononitrile.
(
[a]
sults are listed in Table 2. In general, aryl iodides sub-
stituted with electron-donating groups were smoothly
transformed to the corresponding products in moder-
ate to excellent yields ranging from 60% to 86%
(
Table 2, entries 1–10), whereas electron-withdrawing
substituents resulted in lower yields (40–54%)
Table 2, entries 11–14). Furthermore, the catalytic
[b]
Entry Cu source Ligand
Base
Yield [%]
(
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCN
CuCl
CuBr
phen
phen
phen
phen
phen
phen
phen
phen
phen
phen
phen
phen
t-BuONa 43
MeONa 39
system could tolerate a variety of functionalized aryl
iodides in the reaction, including ether, amino, hy-
droxy, nitro, and acetyl groups (Table 2, entries 5–13).
The steric hindrance of the substituent had a signifi-
cant effect on the results. For example, p-iodotoluene
gave the desired product in 73% yield, while o-iodo-
toluene afforded the corresponding product in a rela-
tively lower yield of 63% (Table 2, entries 2 and 3).
Heterocyclic compounds, such as o-iodopyridine and
m-iodopyridine could also afford the corresponding
products in 50% and 54% yields, respectively
EtONa
21
i-PrONa 27
Cs CO
trace
2
3
K CO
Et N
3
trace
36
2
3
t-BuONa 26
t-BuONa 35
t-BuONa 33
t-BuONa 37
t-BuONa 32
t-BuONa 41
t-BuONa 46
t-BuONa 54
t-BuONa trace
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
Cu O
2
CuCl2
Cu ACHTUNGTRENNUNG( acac) phen
CuO
2
(
Table 2, entries 15 and 16). Notably, the reaction can
phen
be easily carried out on a gram scale albeit with
a slightly diminished yield (Table 2, entry 5).
To seek the catalytic mechanism, we isolated the
main product from the reaction of malononitrile, Cu-
Cu
–
Cu
Cu
ACHTUNGTRENNUNG( OAc) phen
2
phen
(OAc) l-proline
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
t-BuONa
5
8
3
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) 2-picolinic acid t-BuONa
2
Cu
Cu
Cu
Cu
Cu
Cu
Cu
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) bipyridine
t-BuONa
ACHTUNGTNERNGNU( OAc) , 1,10-phenanthroline, t-BuONa and KF in
2
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc)
–
t-BuONa trace
DMF at 1208C, which was proved [16]to be
[Cu(phen)(CN) ] (3) as shown in Scheme 2. It was
then reacted with p-iodoanisole to give the product in
3% yield in the presence or absence of KF
2
[
c]
d]
e]
f]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) phen
t-BuONa 58[
ACHTUNGTRENNUNG
2
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) phen
t-BuONa 46
2
[
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) phen
t-BuONa 75[
2
9
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) phen
t-BuONa 34
t-BuONa 51
2
(
Scheme 3).
g]
ACHTUNGTRENNUNG( OAc) phen
2
Thus, the catalytic mechanism based on these re-
[
a]
Unless otherwise noted, the reactions were carried out sults is proposed: Firstly, a coordination complex
by using 4-iodotoluene (0.2 mmol), malononitrile [Cu
0.4 mmol), base (0.4 mmol), Cu source (0.02 mmol) and
ACHTUNGTNERNGNU( phen)(CN) ] (3) is formed through copper-cata-
2
(
lyzed cleavage of CÀCN bonds in malononitrile assist-
ligand (0.04 mmol) in 1 mL DMF at 1108C for 18 h;
phen=1,10-phenanthroline.
Determined by GC using 1,4-dichlorobenzene as internal
standard.
Reaction temperature was 1208C.
LiCl (0.4 mmol) was used at 1208C.
KF (0.4 mmol) was used at 1208C.
KI (0.4 mmol) was used at 1208C.
[5]
ed by KF. Then, it is reacted with aryl iodides to
give the desired aryl nitriles 2. It is fundamentally dif-
ferent from the mechanism in Scheme 1 A and B,
both of which were reported to proceed through a C-
[
b]
[
[
[
[
[
c]
d]
e]
f]
[
15]
arylation reaction.
In summary, we have developed an efficient
copper-catalyzed method for the synthesis of aryl ni-
g]
3
2
CaF (0.4 mmol) was used at 1208C.
triles by cyano group transfer from C AHCTNUGTRENNGNU( sp ) to C ACHTUNGTRENNUNG( sp ).
2
590
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 589 – 592

Copper-Catalyzed Cyanation of Aryl Iodides with Malononitrile
Table 2. Copper-catalyzed cyanation of different aryl iodides
[a]
with malononitrile.
Ent-
ry
Ar-X
Ar-CN
Yield
[%]
[
b]
Scheme 2. Preparation of the cyanide complex of copper.
1
2
3
73
73
68
61
4
8
6
[
5
6
7
c]
(
82)
Scheme 3. Reaction of [Cu ACHTUNGTERNNUN(G phen)(CN) ](3) with p-iodoani-
2
sole.
82
75
The protocol uses Cu ACHTUNGTERNN(UNG OAc) and 1,10-phenanthroline
2
as catalyst. It is noteworthy that the method develops
another possibility for reactions between aryl iodides
and malononitrile besides the arylation reaction and
oxidative synthesis of aromatic carboxylic acids.
8
9
79
60
80
49
Experimental Section
1
1
0
1
General Procedure
Aryl iodides (0.5 mmol), malononitrile (1 mmol), Cu ACHTUNGTRENNUNG( OAc)
2
(
(
0.05 mmol), 1,10-phenanthroline (0.1 mmol), t-BuONa
1 mmol) and KF (1 mmol) in DMF (2 mL) were added to
1
1
1
1
1
2
3
4
5
6
47
40
52
50
54
a sealed tube. The reaction mixture was stirred at 1208C for
8 h. After completion of the reaction, the solution was di-
luted with dichloromethane, washed with water and brine.
1
The organic layer was then dried over anhydrous Na SO4
2
and the solvent was removed under vacuum. The residue
was finally purified by column chromatography on silica gel
using petroleum ether-ethyl acetate mixture as eluent.
Acknowledgements
We appreciate the Natural Science Foundation of China (No.
21072132), Sichuan Provincial Foundation (08ZQ026-041),
and Ministry of Education (NCET-10-0581) for financial
support and the Analytical & Testing Centre of Sichuan Uni-
versity for NMR analysis.
[
a]
Unless otherwise noted, all reactions were carried out
with aryl iodide (0.5 mmol), malononitrile (1 mmol),
Cu
t-BuONa (1 mmol) and KF (1 mmol) in DMF (2 mL) at
208C.
Isolated yields.
ACHTUNGTRENNUNG( OAc) (0.05 mmol), 1,10-phenanthroline (0.1 mmol),
2
1
[
[
b]
c]
5-mmol scale in brackets.
Adv. Synth. Catal. 2012, 354, 589 – 592
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
591

Zhaoqiong Jiang et al.
COMMUNICATIONS
References
[8] a) Y. Nakao, S. Oda, T. Hiyama, J. Am. Chem. Soc.
2
004, 126, 13904; b) Y. Nakao, Y. Hirata, T. Hiyama, J.
[
1] a) M. Murakami, T. Matsuda, Chem. Commun. 2011,
7, 1100; b) C. Jun, Chem. Soc. Rev. 2004, 33, 610;
c) S. M. Bonesi, M. Fagnoni, Chem. Eur. J. 2010, 16,
3572.
Am. Chem. Soc. 2006, 128, 7420; c) Y. Nakao, S. Ebata,
A. Yada, T. Hiyama, M. Ikawa, S. Ogoshi, J. Am.
Chem. Soc. 2008, 130, 12874; d) Y. Hirata, T. Inui, Y.
Nakao, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 6624;
e) Y. Hirata, T. Yukawa, N. Kashihara, Y. Nakao, T.
Hiyama, J. Am. Chem. Soc. 2009, 131, 10964; f) Y.
Nakao, A. Yada, T. Hiyama, J. Am. Chem. Soc. 2010,
4
1
[
[
2] M. Tobisu, N. Chatani, Chem. Soc. Rev. 2008, 37, 300,
and references cited therein.
3] Y. Hirata, A. Yada, E. Morita, Y. Nakao, T. Hiyama,
M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2010, 132,
1
32, 10024; g) C. Nꢃjera, J. M. Sansano, Angew. Chem.
2
009, 121, 2488; Angew. Chem. Int. Ed. 2009, 48, 2452;
1
0070.
h) N. R. Rondla, S. M. Levi, J. M. Ryss, R. A. V. Berg,
C. J. Douglas, Org. Lett. 2011, 13, 1940.
[
4] a) M. R. Grochowski, T. Li, W. W. Brennessel, W. D.
Jones, J. Am. Chem. Soc. 2010, 132, 12412; b) M.
Ochiai, H. Hashimoto, H. Tobita, Angew. Chem. 2007,
[
9] A. Kleemann, J. Engel, B. Kutscher, D. Reichert, Phar-
maceutical substances: syntheses, patents, applications,
1
19, 8340; Angew. Chem. Int. Ed. 2007, 46, 8192; c) J.
4
th edn., Georg Thieme Verlag, Stuttgart, 2001.
Mꢂller, C. Wꢂrtele, O. Walter, S. Schindler, Angew.
Chem. 2007, 119, 7922; Angew. Chem. Int. Ed. 2007, 46,
[
[
10] TMSCN as cyanide sources, see: M. J. Beller, J. Orga-
nomet. Chem. 2003, 684, 50.
11] Acetone cyanohydrin as cyanide sources, see: a) M.
Sundermeier, A. Zapf, M. Beller, Angew. Chem. 2003,
7
775; d) L. Guo, S. Bao, Y. Li, L. Zheng, Chem.
Commun. 2009, 2893.
[
5] Copper-catalyzed cleavage of CÀCN bonds to form
1
15, 1700; Angew. Chem. Int. Ed. 2003, 42, 1661; b) H.
copper cyanide complexes, see: a) D. S. Marlin, M. M.
Cristau, A. Ouali, J. Spindler, M. Taillefer, Chem. Eur.
J. 2005, 11, 2483; c) T. Schareina, A. Zapf, A. Cottꢄ, M.
Gotta, M. Beller, Adv. Synth. Catal. 2011, 353, 777.
Olmstead, P. K. Mascharak, Angew. Chem. 2001, 113,
4
888; Angew. Chem. Int. Ed. 2001, 40, 4752; b) T. Lu,
X. Zhuang, Y. Li, S. Chen, J. Am. Chem. Soc. 2004,
[
12] For a review on cyanations of aryl halides, see: a) G. P.
1
2
26, 4760; c) F. Xu, W. Huang, X. You, Dalton Trans.
010, 39, 10652; d) L. Yang, Y. Li, X. Zhuang, L. Jiang,
Ellis, T. M. Romney-Alexander, Chem. Rev. 1987, 87,
7
79; b) M. Sundermeier, A. Zapf, M. Beller, Eur. J.
J. Chen, R. L. Luck, T. Lu, Chem. Eur. J. 2009, 15,
2399.
Inorg. Chem. 2003, 3513; c) M. Sundermeier, A. Zapf,
S. Mutyala, W. Baumann, J. Sans, S. Weiss, M. Beller,
Chem. Eur. J. 2003, 9, 1828.
1
[
6] For use of the cyano group as leaving group, see: a) D.
Yu, M. Yu, B. Guan, B. Li, Y. Zheng, Z. Wu, Z. Shi,
Org. Lett. 2009, 11, 3374; b) Y. Kita, M. Tobisu, N. Cha-
tani, Org. Lett. 2010, 12, 1864; c) M. Tobisu, Y. Kita, Y.
Ano, N. Chatani, J. Am. Chem. Soc. 2008, 130, 15982;
d) M. Tobisu, R. Nakamura, Y. Kita, N. Chatani, J. Am.
Chem. Soc. 2009, 131, 3174; e) M. Tobisu, Y. Kita, N.
Chatani, J. Am. Chem. Soc. 2006, 128, 8152.
[
13] F. Luo, C. Chu, C. Cheng, Organometallics 1998, 17,
1
025.
[
14] Arylation of aryl halides with malononitrile, see: a) H.
Suzuki, T. Kobayashi, A. Osuka, Chem. Lett. 1983, 589;
b) K. Okuro, M. Furuune, M. Miura, M. Nomura, J.
Org. Chem. 1993, 58, 7606.
[15] D. Yang, H. Yang, H. Fu, Chem. Commun. 2011, 47,
2348.
[
7] K. Nozaki, N. Sato, H. Takaya, J. Org. Chem. 1994, 59,
2
679.
[16] M. Wicholas, T. Wolford, Inorg. Chem. 1974, 13, 316.
592
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 589 – 592