Y. Ren et al. / Tetrahedron Letters 50 (2009) 4595–4597
4597
MCN
MI
wave heating. The suggested methodology was applicable to a
wide range of substrates including aryl iodides and activated aryl
bromides. In addition, the cyanated product could be quantita-
tively separated from the reaction mixture, and the recovered
aqueous phase containing the catalyst could be reused for six times
with a very slight change in the catalytic activity.
MI
Br
I
CN
MBr
More reactive
Scheme 1. Copper-catalyzed domino halide exchange-cyanation of bromobenzene.
Acknowledgments
9
6
3
0
0
0
0
The authors wish to thank the financial supports from the Na-
tional High Technology Research and Development Program of Chi-
na (863 Program, Grant No. 2007AA05Z454) and the Innovation
Scientists and Technicians Troop Construction Projects of Henan
Province (Grant No. 084200510015).
1
2
3
4
5
6
7
Recycle times of the catalyst
Supplementary data
Figure 1. Reuse of the catalyst for Cu(OAc)
zene under the reaction conditions as shown in entry 17, Table 1.
2
ꢀH
2
O-catalyzed cyanation of iodoben-
protocol. Although a protocol with DMEDA/Cu(OAc)
catalytic system was also effective (Table 1, entry 18), we preferred
the ligand-free methodology for economic reason (Table 1, entry
2
ꢀH
2
O as the
References and notes
1. Larock, R. C. In Comprehensive Organic Transformations; VCH: New York, 1989;
pp 819–995.
1
7). As summarized in Table 2, the cyanation of various aryl io-
2.
Rappoport, Z. In Chemistry of the Cyano Group; John Wiley & Sons: London,
970; pp 121–312.
dides gave the corresponding aromatic nitriles in moderate to
excellent yields. In addition, the reactions were able to tolerate a
wide range of functional groups such as ketone carbonyl, ester, ni-
tryl, nitrile, methoxy, and hydroxy groups. Primary amido group
was even well tolerated and did not suffer from N-arylation (Table
1
3. (a) Lindley, J. Tetrahedron 1984, 40, 1433–1456; (b) Rosenmund, K. W.; Struck,
E. Ber. Dtsch. Chem. Ges. 1919, 2, 1749–1755.
4
5
.
.
Wang, D. P.; Kuang, L. P.; Li, Z. W.; Ding, K. Synlett 2008, 2008, 69–72.
For two reviews see: (a) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg. Chem.
2003, 2003, 3513–3526; (b) Sundermeier, M.; Zapf, A.; Mutyala, S.; Baumann,
W.; Sans, J.; Weiss, S.; Beller, M. Chem. Eur. J. 2003, 9, 1828–1836.
2
, entry 8), which possibly resulted from the high affinity of the
6.
(a) Ryberg, P. Org. Process Res. Dev. 2008, 12, 540–543; (b) Littke, A.;
Soumeillant, M.; Kaltenbach, R. F., III; Cherney, R. J.; Tarby, C. M.; Kiau, S. Org.
Lett. 2007, 9, 1711–1714; (c) Erhardt, S.; Grushin, V. V.; Kilpatrick, A. H.;
Macgregor, S. A.; Marshall, W. J.; Roe, D. C. J. Am. Chem. Soc. 2008, 130, 4828–
8
cyanide nucleophile toward the palladium catalyst. The reactions
appeared to be insensitive to the steric hindrance around the reac-
tion site. For instance, 4-iodotoluene gave a yield of 81%, while 2-
iodotoluene with a bigger steric hindrance around the reaction site
also gave a high yield (Table 2, entries 13 and 14).
4845; (d) Grossman, O.; Gelman, D. Org. Lett. 2006, 8, 1189–1191.
7.
Pongratz, A. Monatsh. Chem. 1927, 48, 585–591.
8. Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 2890–2891.
Schareina, T.; Zapf, A.; Beller, M. Tetrahedron Lett. 2005, 46, 2585–2588.
0. Cristau, H. J.; Ouali, A.; Spindler, J. F.; Taillefer, M. Chem. Eur. J. 2005, 11, 2483–
492.
9.
The cyanation of several aryl bromides gave very low yields
1
(
Table 2, entries 17 and 23), which urged us to use KI as an additive
to improve the reaction. As shown in Table 2 (entries 20–22 and
4), the KI-accelerated protocol allowed several aryl bromides
2
11. (a) Schareina, T.; Zapf, A.; Mägerlein, W.; Müller, N.; Beller, M. Chem. Eur. J.
2007, 13, 6249–6254; (b) Schareina, T.; Zapf, A.; Mägerlein, W.; Müller, N.;
Beller, M. Synlett 2007, 555–558; (c) Schareina, T.; Zapf, A.; Cotté, A.; Müller, N.;
Beller, M. Synthesis 2008, 2008, 3351–3355.
2
bearing electron-withdrawing groups to be cyanated in satisfying
7
yields. According to a related report, the KI-accelerated effect re-
12. Ren, Y. L.; Liu, Z. F.; Zhao, S.; Tian, X. Z.; Wang, J. J.; Yin, W. P.; He, S. B. Catal.
sulted possibly from a conversion of the aryl bromide into the
more reactive aryl iodide (Scheme 1). Although aryl bromides bear-
ing electron-donating groups did not act as the effective substrates
Commun. 2009, 10, 768–771.
3. (a) Buffin, B. P.; Belitz, N. L.; Verbeke, S. L. J. Mol. Catal. A: Chem. 2008, 284, 149–
1
154; (b) Buffin, B. P.; Clarkson, J. P.; Belitz, N. L.; Kundu, A. J. Mol. Catal. A: Chem.
2005, 225, 111–116; (c) Gan, K. H.; Jhong, C. J.; Shue, Y. J.; Yang, S. C.
(
Table 2, entries 25 and 27), an additional use of DMEDA allowed
Tetrahedron 2008, 64, 9625–9629; (d) Gan, K. H.; Jhong, C. J.; Yang, S. C.
Tetrahedron 2008, 64, 1204–1212; (e) Yang, S. C.; Hsu, Y. C.; Gan, K. H.
Tetrahedron 2006, 62, 3949–3958.
the unactivated aryl bromides to be cyanated smoothly (Table 2,
entries 19, 26, and 28).
1
4. Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563–2591.
Finally, our investigation was focused on the reuse of the li-
gand-free catalyst. When 0.5 mL n-pentane was added to the reac-
tion mixture at the end of the reaction, a two-phase mixture was
obtained. After the organic layer containing benzonitrile product
was separated, the recovered aqueous phase containing the cata-
lyst could be reused for six times with a very slight change in
the catalytic activity (Fig. 1).
In conclusion, a practical and environmentally benign method-
ology for Cu-catalyzed cyanation of aryl halides was well devel-
oped with some main innovations: the use of water as the
15. Typical procedure for the cyanation of aryl halides: In a 10 mL microwave tube
copper salt (0.1 mmol), K [Fe(CN) O (123 mg, 0.3 mmol), TBAB (323 mg,
]ꢀ3H
mmol), and aryl halide (1 mmol) were placed. After adding water (2 mL),
4
6
2
1
the vessel was sealed with a septum and was placed into the microwave
cavity. Initial microwave irradiation of 600 W was used, the temperature
being ramped from room temperature to the desired temperature of 140 °C.
Once this was reached, the reaction mixture was held at this temperature
until a total time of 50 min had elapsed. Then the mixture was cooled to
room temperature and the desired product was extracted with diethyl ether
(3 ꢁ 5 mL). Evaporation of the solvent was followed by the GC analysis of
corresponding products. Then, the cyanation product was purified by
column chromatography. All the products are known compounds and were
identified by comparison of their 1
literature data.
13
H
NMR and
C NMR data with the
solvent and ligand-free Cu(OAc)
2
2
ꢀH O as the catalyst under micro-