LETTER
Copper-Catalyzed Oxidative Cyanation
2495
an oxidant to promote both H C–CN σ-bond and C–X
bond cleavage.
II; Gould, R. F., Ed.; American Chemical Society:
Washington, 1974, Chap. 17, 252–273.
5) For selected reviews, see: (a) Schareina, T.; Zapf, A.; Beller,
M. Chem. Commun. 2004, 1388. (b) Grushin, V. V.; Alper,
H. Chem. Rev. 1994, 94, 1047. (c) Ellis, G. A.; Romney-
Alexander, T. M. Chem. Rev. 1987, 87, 779.
3
(
[Cu]
L
I
(6) For selected papers, see: (a) For KCN, see: Li, C.; Ju, Y.;
Liu, F. Org. Lett. 2009, 11, 3582. (b) Arai, S.; Sato, T.;
Nishida, A. Adv. Synth. Catal. 2009, 351, 1897. (c) Yang,
C.; Williams, J. M. Org. Lett. 2004, 6, 2837. (d) For NaCN,
see: Zhang, Z.; Wang, Z.; Zhang, R.; Ding, K. Angew. Chem.
Int. Ed. 2010, 49, 6746. (e) Do, H.-Q.; Daugulis, O. Org.
Lett. 2010, 12, 2517. (f) Murahashi, S.-I.; Nakae, T.; Terai,
H.; Komiya, N. J. Am. Chem. Soc. 2008, 130, 11005.
Cu LnOAc
Ar X + [Ag]
1
Ar CN
[Ag]X
Ar
III
Cu LnOAc
II
Ar Cu LnOAc
CN
III
I
(g) Erhardt, S.; Grushin, V. V.; Kilpatrick, A. H.;
Macgregor, S. A.; Marshall, W. J.; Roe, D. C. J. Am. Chem.
Soc. 2008, 130, 4828. (h) Ushkov, A. V.; Grushin, V. V.
J. Am. Chem. Soc. 2011, 133, 10999. (i) Cristau, H.-J.;
Ouali, A.; Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2005,
11, 2483. (j) For CuCN, see: Reddy, B. V. S.; Begum, Z.;
Reddy, Y. J.; Yadav, J. S. Tetrahedron Lett. 2010, 51, 3334.
Me
Me
2
C
N
C
N
a
HCOOH + AgX
II
Ar Cu Ln–1OAc
L
O2/Ag2O + L
II
Scheme 4 Possible mechanism
(
k) For Zn(CN) , see: Liskey, C. W.; Liao, X.; Hartwig, J. F.
2
J. Am. Chem. Soc. 2010, 132, 11389. (l) Shevlin, M.
Tetrahedron Lett. 2010, 51, 4833. (m) Buono, F. G.;
Chidambaram, R.; Mueller, R. H.; Waltermire, R. E. Org.
Lett. 2008, 10, 5325. (n) Littke, A.; Soumeillant, M.;
Kaltenbach, R. F. III.; Cherney, R. J.; Tarby, C. M.; Kiau, S.
Org. Lett. 2007, 9, 1711. (o) For [K Fe(CN) ], see: Yeung,
P. Y.; So, C. M.; Lau, C. P.; Kwong, F. Y. Angew. Chem. Int.
Ed. 2010, 49, 8918. (p) DeBlase, C.; Leadbeater, N. E.
Tetrahedron 2010, 66, 1098. (q) Yan, G.; Kuang, C.; Zhang,
Y.; Wang, J. Org. Lett. 2010, 12, 1052. (r) Zhao, Z.; Li, Z.
Eur. J. Org. Chem. 2010, 5460. (s) Velmathi, S.; Leadbeater,
N. E. Tetrahedron Lett. 2008, 49, 4693. (t) For TMSCN, see:
Arai, S.; Koike, Y.; Nishida, A. Adv. Synth. Catal. 2010,
In summary, we have developed a novel, general copper-
catalyzed oxidative cyanation with aryl halides using
commercially available acetonitrile as the cyanide sources
and Ag O/air as the oxidizing agent. Importantly, this
2
4
6
work provides a new example of using MeCN as the cya-
nide source and solvent for preparing aromatic nitriles
with high tolerance of functional groups, including sub-
strates with free OH or NH groups, through a Cu-cata-
2
lyzed oxidative C–C bond cleavage and cyanation with
aryl halides. The mechanism was also discussed in light of
the present results and the reaction profiles.
352, 893. (u) Arai, S.; Sato, T.; Koike, Y.; Hayashi, M.;
Nishida, A. Angew. Chem. Int. Ed. 2009, 48, 4528. (v) Han,
W.; Ofial, A. R. Chem. Commun. 2009, 5024. (w) Chen, G.;
Wang, Z.; Wu, J.; Ding, K. Org. Lett. 2008, 10, 4573. (x) For
MeCN, see: Guo, F.-H.; Chu, C.-I.; Cheng, C.-H.
Organometallics 1998, 17, 1025. (y) For nitriles, see:
Garcia, J. J.; Jones, W. D. Organometallics 2000, 19, 5544.
Acknowledgment
We thank the National Natural Science Foundation of China (No.
2
1172060), the Fundamental Research Funds for the Central Uni-
versities (Hunan university), and the China Postdoctoral Science
Foundation (No.2012 M511716) for financial support.
(z) For other CN sources, see: Garcia, J. J.; Brunkan, N. M.;
Jones, W. D. J. Am. Chem. Soc. 2002, 124, 9547. (aa) Zhang,
G.; Ren, X.; Chen, J.; Hu, M.; Cheng, J. Org. Lett. 2011, 13,
5004.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SuppInigfor
m
ti
o
(7) For a representative paper on the use of Me C(OH)CN as the
2
cyanide source, see: (a) Schareina, T.; Zapf, A.; Cotté, A.;
Gotta, M.; Beller, M. Adv. Synth. Catal. 2011, 353, 777; and
references cited therein. (b) Park, E. J.; Lee, S.; Chang, S. J.
Org. Chem. 2010, 75, 2760.
References and Notes
(1) For selected recent reviews, see: (a) Anbarasan, P.;
(
8) For selected papers on the cyanation of arene C–H bonds
through C–H activation, see: (a) Kim, J.; Chang, S. J. Am.
Chem. Soc. 2010, 132, 10272. (b) Jia, X.; Yang, D.; Zhang,
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(
c) Jones, L. H.; Summerhill, N. W.; Swain, N. A.; Mills,
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Zapf, A.; Beller, M. Eur. J. Inorg. Chem. 2003, 3513.
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(
(
9) For representative papers on the use of RCN as cyanide
sources for addition with alkynes using Ni/AlMe , see:
3
(
2
a) Nakao, Y.; Yada, A.; Hiyama, T. J. Am. Chem. Soc.
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(
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(
(
b) Cassar, L.; Ferrara, S.; Foa, M. Homogeneous Catalysis
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Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2491–2496