H.-J. Xu et al. / Tetrahedron Letters 51 (2010) 669–671
671
(
Table 2, entries 1–4). The reactions of N-heterocycles with aryl io-
W.; Liu, L.; Zhang, C.; Liu, M.; Guo, Q. X. Tetrahedron Lett. 2005, 46, 7295; (r)
Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M. Chem. Eur. J. 2004, 10,
dide moieties (Table 2, entries 16–19) and of alkyl amine with het-
eroaryl iodide (Table 2, entry 5 and 12) were successful in the
protocol, leading to the desired products in good yields. On the ba-
sis of the successful examples, the coupling reactions of alkyl
amines with aryl bromides (Table 2, entries 6–8, 13–15, and 20–
5607; (s) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. A. J. Org. Chem.
2004, 69, 5578; (t) Deng, W.; Wang, Y. F.; Zou, Y.; Liu, L.; Guo, Q. X. Tetrahedron
Lett. 2004, 45, 2311; (u) Antilla, J. C.; Klapars, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 11684; (v) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J.
Am. Chem. Soc. 2001, 123, 7727.
(a) Okano, K.; Tokuyama, H.; Fukuyama, T. Org. Lett. 2003, 5, 4987; (b) Kelkar, A.
A.; Patil, N. M.; Chaudhari, R. V. Tetrahedron Lett. 2002, 43, 7143; (c) Zhu, L.;
Guo, P.; Li; Lan, J.; Xie, R.; You, J. J. Org. Chem. 2007, 72, 8535; (d) Zhu, L.; Li, G.;
Luo, L.; Guo, P.; Lan, J.; You, J. J. Org. Chem. 2009, 74, 2200; (e) Zhu, R.; Xing, L.;
Wang, X.; Cheng, C.; Su, D.; Hu, Y. Adv. Synth. Catal. 2008, 350, 1253; (f) Correa,
A.; Bolm, C. Adv. Synth. Catal. 2007, 349, 2673.
4
.
.
2
3) were also explored and moderate yields were obtained. How-
ever, to our disappointment, the N-arylations of alkyl amines and
N-heterocycles with aryl chlorides were not observed in the pres-
ent protocol.
In conclusion, we developed a practical and simple protocol for
the N-arylations of amines with differently substituted aryl ha-
lides. The aqueous Bu
which plays the role of a phase transfer catalyst (PTC). The results
4 4
obtained were better than those of Me N OH and Et N OH in the
same reaction conditions. The versatility, convenient operation,
and environmental friendliness of this procedure make it easily
transferrable to industrial applications.
1
0
5
(a) Lang, F.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahedron Lett. 2001, 42,
3251; (b) Job, G. E.; Buchwald, S. L. Org. Lett. 2002, 4, 3703; (c) Carril, M.;
SanMartin, R.; Domínguez, E.; Tellitu, I. Green Chem. 2007, 9, 219; (d) Ma, D.;
Xia, C. Org. Lett. 2001, 3, 2583; (e) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem.
n
+
À
4
N OH was used as a base and as a solvent
2005, 70, 8107; (f) Liu, L.; Frohn, M.; Xi, N.; Dominguez, C.; Hungate, R.; Reider,
+
À
+
À
P. J. J. Org. Chem. 2005, 70, 10135; (g) Lu, Z.; Twieg, R. J.; Huang, S. D.
Tetrahedron Lett. 2003, 44, 6289; (h) Lu, Z.; Twieg, R. J. Tetrahedron Lett. 2005,
46, 2997; (i) Zhu, X.; Ma, Y.; Su, L.; Song, H.; Chen, G.; Liang, D.; Wan, Y.
Synthesis 2006, 3955; (j) Carril, M.; SanMartin, R.; Domínguez, E. Chem. Soc. Rev.
2008, 37, 639; (k) Teo, Y. C. Adv. Synth. Catal. 2009, 351, 720.
6.
(a) Siskin, M.; Katritzky, A. R. Chem. Rev. 2001, 101, 825; (b) Lindström, U. M.
Chem. Rev. 2002, 102, 2751; (c) Kobayahi, S.; Manabe, K. Acc. Chem. Res. 2002,
35, 209; (d) Akiya, N.; Savage, P. E. Chem. Rev. 2002, 102, 2725; (e) DeSimone, J.
M. Science 2002, 297, 799; (f) Poliakoff, M.; Fitzpatrick, J. M.; Farren, T. R.;
Anastas, P. T. Science 2002, 297, 807; (g) Li, C. J. Chem. Rev. 2005, 105, 3095; (h)
Blackmond, D. G.; Armstrong, A.; Coombe, V.; Wells, A. Angew. Chem., Int. Ed.
2007, 46, 3798; (i) Minakata, S.; Komatsu, M. Chem. Rev. 2008, 108, 825.
Yadav, L. D. S.; Yadav, B. S.; Rai, V. K. Synthesis 2006, 1868.
Acknowledgment
This research was financially supported by the National Natural
Science Foundation of China (Nos. 20802015, 20772115).
7
8
.
.
Feng, Y. S.; Man, Q. S.; Pan, P.; Pan, Z. Q.; Xu, H. J. Tetrahedron Lett. 2009, 50,
References and notes
2585.
9.
General experimental procedure. A Schlenk tube was charged with Cu salt
(0.1 mmol) and solid substrate, if present, evacuated, and backfilled with argon
three times. Then, liquid reagents (aryl halides or alkyl amines and N-
heterocycles), 40% aq base solutions (1 mL) were added under Ar. The reaction
vessel was closed and placed under stirring in a preheated oil bath at 80 °C. The
reaction mixture was stirred for 24 h. The mixture was cooled to room
temperature and partitioned between ethyl acetate and aq HCl, the organic
layer was washed with water, dried over Na SO , and concentrated in vacuo.
1
.
For general reviews, see: (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev.
004, 248, 2337; (b) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318; (c) Corbert, J. P.; Mignani, G. Chem. Rev. 2006, 106,
651; (d) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400.
For reviews, see: (a) Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003, 2428; (b)
Deng, W.; Liu, L.; Guo, Q. X. Chin. J. Org. Chem. 2004, 24, 150; (c) Evano, G.;
Blanchard, N.; Toumi, T. Chem. Rev. 2008, 108, 3054; (d) Monnier, F.; Taillefer,
M. Angew. Chem., Int. Ed. 2009, 48, 6954; (e) Ma, D.; Cai, Q. Acc. Chem. Res. 2008,
2
2
2
.
2
4
The residue was purified by silica gel chromatography to provide the desired
4
1, 1450.
For some important examples, see: (a) Wang, D.; Ding, K. Chem. Commun. 2009,
891; (b) Yang, C. T.; Fu, Y.; Huang, Y. B.; Yi, J.; Guo, Q. X.; Liu, L. Angew. Chem.,
product. Selected spectral and analytical1 data for N-Benzyl-4-
3
.
methoxybenzenamine (Table 2, entries 1 and 6): H NMR (300 MHz, CDCl , d
3
1
ppm): 7.36–7.26 (m, 5H), 6.78 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 8.4 Hz, 2H), 4.29 (s,
2H), 3.74 (s, 3H); 13C NMR (75 MHz, CDCl , d ppm): 152.4, 142.5, 139.8, 128.7,
Int. Ed. 2009, 48, 7398; (c) Strieter, E. R.; Bhayana, B.; Buchwald, S. L. J. Am.
Chem. Soc. 2009, 131, 78; (d) Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee, T.;
Mandai, S.; Mitra, R.; Saha, P.; Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971;
3
127.6, 127.3, 115.1, 114.3, 55.9, 49.4. HRMS calcd C14H15NO: 213.1154. Found:
1
213.1160. N-Hexyl-4-methylbenzenamine (Table 2, entries 10 and 13): H NMR
(
e) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed. 2008, 47, 3096; (f) Wu, M.;
(300 MHz, CDCl , d ppm): 6.97 (d, J = 8.1 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 3.07 (t,
3
Mao, J.; Gou, J.; Ji, S. Eur. J. Org. Chem. 2008, 4050; (g) Tao, C. Z.; Li, J.; Fu, Y.; Liu,
L.; Guo, Q. X. Tetrahedron Lett. 2008, 49, 70; (h) Rout, L.; Jammi, S.;
Puniyamurthy, T. Org. Lett. 2007, 9, 3397; (i) Yang, M.; Liu, F. J. Org. Chem.
J = 7.0 Hz, 3H), 2.22 (s, 3H), 1.61 (m, 2H), 1.37 (m, 6H), 0.91 (t, J = 6.3 Hz, 3H);
13
C NMR (75 MHz, CDCl , d ppm): 146.2, 129.7, 126.5, 113.1, 44.6, 31.7, 30.9,
3
29.6, 26.9, 22.7, 20.4, 14.1. HRMS calcd C13H21N: 191.1674. Found: 191.1678. 1-
1
2
007, 72, 8969; (j) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863; (k) Tao, C. Z.; Cui,
p-tolyl-1H-pyrrole (Table 2, entries 16 and 20): H NMR (300 MHz, CDCl , d
3
X.; Li, J.; Liu, A. X.; Liu, L.; Guo, Q. X. Tetrahedron Lett. 2007, 48, 3525; (l) Rao, H.;
Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Chem. Eur. J. 2006, 12, 3636; (m) Xie, Y.; Pi, S.;
Wang, J.; Yin, D.; Li, J. J. Org. Chem. 2006, 71, 8324; (n) Altman, R. A.; Buchwald,
S. L. Org. Lett. 2006, 8, 2779; (o) Liu, L.; Frohn, M.; Xi, N.; Domínguez, C.;
Hungate, R.; Reider, P. J. J. Org. Chem. 2005, 70, 10135; (p) Jerphagnon, T.; van
Klink, G. P. M.; de Vries, J. G.; van Koten, G. Org. Lett. 2005, 7, 5241; (q) Deng,
ppm): 7.29–7.20 (m, 4H), 7.05 (d, J = 1.5 Hz, 2H), 6.33 (d, J = 1.5 Hz, 2H), 2.36 (s,
3H); 13C NMR (75 MHz, CDCl , d ppm): 138.6, 135.3, 130.1, 120.5, 119.4, 110.1,
3
20.8. HRMS calcd C11H11N: 157.0891. Found: 157.0895.
10. Studies on mechanism of N-arylation of amines catalyzed by copper, see:
Zhang, S. L.; Liu, L.; Fu, Y.; Guo, Q. X. Organometallics 2007, 26, 4546.