3108
B. de Lange et al.
LETTER
Table 3 Ligand Screening in Copper-Catalysed Aminationa
References and Notes
R1
(1) For some recent applications in the pharmaceutical field,
see: (a) Gosh, A.; Sieser, J. E.; Caron, S.; Couturier, M.;
Dupont-Gaudet, K.; Girardin, M. J. Org. Chem. 2006, 71,
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2006, 62, 1110. (c) Damon, D. B.; Dugger, R. W.; Hubbs, S.
E.; Scott, J. M.; Scott, R. W. Org. Process Res. Dev. 2006,
10, 472.
R1
CuCl (10 mol%)
ligand (25 mol%)
R2
R3
R2
R3
N
X
+
HN
K2CO3, NMP,
130 °C, 16 h
Entry Aryl-Hal
Amine
Ligand
(25 mol%) (%)
Yield
(2) Kisselev, R.; Thelakkat, M. Chem. Commun. 2002, 1530.
(3) Wu, J.; Watson, M. D.; Müllen, K. Angew. Chem. Int. Ed.
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Lett. 2002, 43, 7143.
1
2
Bromobenzene Piperidine
1a
1c
2a
2b
2c
3a
3b
3c
2a
2c
3a
3c
1c
3b
3c
1a
1c
2a
3a
40
74
70
70
70b
95
74
95
40
40
85
85
31c
36c
5
3
4
5
(5) Suo, Z.; Drobizhev, M.; Spangler, C. W.; Christensson, N.;
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6
7
(6) (a) Ullmann, F. Ber. Dtsch. Chem. Ges. 1903, 36, 2382.
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(b) For a recent catalyst, see: Klapars, A.; Huang, X.;
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8
9
4-Bromoanisole Piperidine
2-Bromoanisole Piperidine
10
11
12
13
14
15
16
17
18
19
Chlorobenzene Piperidine
Bromobenzene Morpholine
16
44
26
(10) Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64, 670.
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Bekedam, E. K.; Visser, G. M.; van den Hoogenband, A.;
45
(65)d
20
21
22
23
24
25
26
27
3c
50
15
30
88d
45
30
65e
80
Bromobenzene N-Methylpiperazine 1a
2a
3a
3c
Bromobenzene Aniline
1a
1c
3a
a Conditions: aryl halide, 5 M in NMP, amine (1.2 equiv), CuCl (10
mol%), K2CO3 (1.05 equiv), 130 °C, 16–48 h.
b Amine (1.5 equiv).
c A 60% selectivity to anisole.
d Amine (2.0 equiv).
e Isolated yield: 57%.
Synlett 2006, No. 18, 3105–3109 © Thieme Stuttgart · New York