Table 4 Comparison of NH
lyzed N-arylation of heteroaryl iodides and aryl bromides
4
Cl and aqueous NH
3
in the Cu-cata-
5. A. Klapars, J. C. Antilla, X. Huang and S. L. Buchwald, J. Am.
Chem. Soc., 2001, 123, 7727.
a
6
. (a) A. Kiyomori, J.-F. Marcoux and S. L. Buchwald, Tetrahedron
Lett., 1999, 40, 2657; (b) J. C. Antilla, J. M. Baskin, T. E. Barder
and S. L. Buchwald, J. Org. Chem., 2004, 69, 5578.
7
. J. C. Antilla, A. Klapars and S. L. Buchwald, J. Am. Chem. Soc.,
2
002, 124, 11684.
. M. Wolter, A. Klapars and S. L. Buchwald, Org. Lett., 2001, 3,
803.
b
Entry
1
Aryl halide
Product
Yield (%)
8
3
45
50
c
9. K. L. Jones, A. Porzelle, A. Hall, M. D. Woodrow and N. C.
O. Tomkinson, Org. Lett., 2008, 10, 797.
2
3
4
61
70
10. (a) F. Y. Kwong, A. Klapars and S. L. Buchwald, Org. Lett., 2002,
4, 581; (b) F. Y. Kwong and S. L. Buchwald, Org. Lett., 2003, 5, 793.
c
1
1. H.-J. Cristau, P. P. Cellier, J.-F. Spindler and M. Taillefer, Eur. J.
Org. Chem., 2004, 695.
12. H-C. Ma and X. -Z. Jiang, J. Org. Chem., 2007, 72, 8943.
5
6
75
90
c
13. (a) D. V. Allen and D. Venkataraman, J. Org. Chem., 2003, 68,
4590; (b) A. Shafir, P. A. Lichtor and S. L. Buchwald, J. Am.
Chem. Soc., 2007, 129, 3490.
14. S. Zhang, D. Zhang and L. S. Liebeskind, J. Org. Chem., 1997, 62,
d
7
8
75
88
cd
2
5. (a) D. Ma, Q. Cai and H. Zhang, Org. Lett., 2003, 5, 2453;
312.
d
9
1
80
91
1
cd
0
(
(
(
(
b) X. Pan, Q. Cai and D. Ma, Org. Lett., 2004, 6, 1809;
c) W. Zhu and D. Ma, Chem. Commun., 2004, 888;
d) H. Zhang, Q. Cai and D. Ma, J. Org. Chem., 2005, 70, 5164;
e) B. Zou, Q. Yuan and D. Ma, Angew. Chem., Int. Ed., 2007, 46,
d
1
1
1
2
10
44
cd
2
598; (f) B. Zou, Q. Yuan and D. Ma, Org. Lett., 2007, 9, 4291;
g) D. Ma, Y. Zhang, J. Yao, S. Wu and F. Tao, J. Am. Chem.
(
Soc., 1998, 120, 12459.
a
Reaction conditions: aryl halide (0.5 mmol), NH
CO (1.5 mmol) in DMSO
Cl was used) under Ar at
(aqueous 28%, 0.75 mmol) was used for
4
Cl (0.65 mmol),
CuI (20 mol%), L-proline (40 mol%), K
2
3
1
6. (a) D. Ma and F. Liu, Chem. Commun., 2004, 1934; (b) X. Xie,
G. Cai and D. Ma, Org. Lett., 2005, 7, 4693; (c) B. Lu and D. Ma,
Org. Lett., 2006, 8, 6115; (d) X. Xie, Y. Chen and D. Ma, J. Am.
Chem. Soc., 2006, 128, 16050; (e) Y. Chen, X. Xie and D. Ma,
J. Org. Chem., 2007, 72, 9329.
(1 mL) and 50 mL of H O (when NH
2 4
b c
2
5 1C. Isolated yield. NH
3
d
2
4 h. Run at 80 1C.
1
1
1
7. (a) Q. Cai, B. Zou and D. Ma, Angew. Chem., Int. Ed., 2006, 45,
1
276; (b) Q. Cai, G. He and D. Ma, J. Org. Chem., 2006, 71, 5268.
8. (a) W. Zhu and D. Ma, J. Org. Chem., 2005, 70, 2696;
b) H. Zhang, W. Cao and D. Ma, Synth. Commun., 2007, 37, 25.
reacted with both ammonium salts at room temperature to
furnish the corresponding coupled products in good yields
(
˚
9. (a) J. P. Wolfe, J. Ahman, J. P. Sadighi, R. A. Singer and
S. L. Buchwald, Tetrahedron Lett., 1997, 38, 6367; (b) G. Mann,
J. F. Hartwig, M. S. Driver and C. Fernandez-Rivas, J. Am.
Chem. Soc., 1998, 120, 827.
(
entries 1–6). Moreover, it was observed that aryl bromides
bearing electron-withdrawing groups were viable substrates
although elevated temperatures were required for satisfactory
yields (entries 7–10). On the other hand, aryl bromides bearing
electron-donating substituents were less effective (entries
2
2
0. (a) S. Lee, M. Jørgensen and J. F. Hartwig, Org. Lett., 2001, 3,
2
729; (b) X. Huang and S. L. Buchwald, Org. Lett., 2001, 3, 3417;
(c) D.-Y. Lee and J. F. Hartwig, Org. Lett., 2005, 7, 1169.
1. For the use of other ammonia equivalents, see: (a) S. Jaime-
Figueroa, Y. Liu, J. M. Muchowski and D. G. Putman, Tetra-
hedron Lett., 1998, 39, 1313; (b) C. W. Lim and S. Lee, Tetra-
hedron, 2000, 56, 5131; (c) C. Bolm and J. P. Hildebrand,
Tetrahedron Lett., 1998, 39, 5731.
1
1–12). In addition, the reaction of aryl chlorides was much
7
more sluggish under the present system.
2
In summary, we have developed an efficient protocol
of room temperature Cu-catalyzed coupling of aryl halides
with inexpensive and convenient ammonium salts. Although
2
2. (a) Q. Shen and J. F. Hartwig, J. Am. Chem. Soc., 2006, 128,
1
0028; (b) D. S. Surry and S. L. Buchwald, J. Am. Chem. Soc.,
2007, 129, 10354; (c) F. Lang, D. Zewge, I. N. Houpis and
R. P. Volante, Tetrahedron Lett., 2001, 42, 3251;
both reagents, NH Cl and aqueous NH solution, can be
3
4
employed as ammonia equivalents in the Cu-catalyzed amina-
tions, the latter species was more effective for the coupling
reaction to afford higher product yields. The present proce-
dure is mild and tolerant of a variety of functional groups,
thus allowing for the practical new route to primary aryl
amines.
(
d) M. C. Willis, Angew. Chem., Int. Ed., 2007, 46, 3402.
3. R. Yamaguchi, S. Kawagoe, C. Asai and K.-i. Fujita, Org. Lett.,
008, 10, 181.
2
2
24. For selected examples of using NH Cl in Cu-catalyzed reactions
4
other than N-arylation, see: (a) H. Hayashi, K. Kawasaki and
T. Murata, Chem. Lett., 1974, 1079; (b) P. Capdevielle, A. Lavigne
and M. Maumy, Synthesis, 1989, 451.
This research was supported by the Korea Research Foun-
dation Grant (KRF-2006-312-C00587).
2
5. For previous reports on the related cross-coupling recations from
this laboratory, see: (a) S. Ko, C. Lee, M.-G. Choi, Y. Na and
S. Chang, J. Org. Chem., 2003, 68, 1607; (b) Y. Na, S. Park,
S. B. Han, H. Han, S. Ko and S. Chang, J. Am. Chem. Soc., 2004,
Notes and references
1
28, 250; (c) S. Park, M. Kim, D. H. Koo and S. Chang, Adv.
1
. M. Negwar, in Organic-Chemical Drugs and their Synonyms:
(An International Survey), Akademie, Berlin, Germany, 7th edn,
Synth. Catal., 2004, 346, 1638; (d) S. Ko, B. Kang and S. Chang,
Angew. Chem., Int. Ed., 2005, 44, 455; (e) L. K. Hwang, Y. Na,
J. Lee, Y. Do and S. Chang, Angew. Chem., Int. Ed., 2005, 44,
6166.
1994.
2
. (a) F. Ullmann, Ber. Dtsch. Chem. Ges., 1903, 36,
382; (b) J. Lindley, Tetrahedron, 1984, 40, 1433.
2
26. See the Electronic Supplementary Information (ESI).
0
3
4
. I. Goldberg, Ber. Dtsch. Chem. Ges., 1906, 39, 1619.
. (a) R. Gujadhur, D. Venkataraman and J. T. Kintigh, Tetra-
hedron Lett., 2001, 42, 4791; (b) R. K. Gujadhur, C. G. Bates and
D. Venkataraman, Org. Lett., 2001, 3, 4315.
27. For example, the reaction of 4 -chloroacetophenone with aqueous
3
NH solution afforded 26% conversion and 5% product yield
using the Cu/proline system at 90 1C. No further attempts to
optimize this reaction have been made.
3
054 | Chem. Commun., 2008, 3052–3054
This journal is ꢀc The Royal Society of Chemistry 2008