quinoline N-oxide with acrylates, ethers, arenes, and in-
doles to construct various CÀC bonds. However, CÀN
bond construction catalyzed by transition metals via dehy-
drogenative coupling of quinoline N-oxide is still a chal-
lenge. Herein, we present a dehydrogenative amination/
amidation of quinoline N-oxides with lactams/cyclamines
to construct 2-aminoquinoline in the presence of the
substrates to screen the conditions of dehydrogenative
coupling. The reaction was performed at 120 °C for 24 h
in a sealed tube. As shown in Table 1, with solely 2 equiv
of Cu(OAc) or Ag CO in the system (entries 1, 2), no
2
2
3
dehydrogenative coupling could proceed. To our delight,
Cu(OAc) catalyst.
2
Table 1. Dehydrogenative Amidation of Quinoline N-Oxide
solvent
(1 mL)
yield
(%)
entry
catalyst
oxidant
1
2
3
4
5
6
7
8
9
Cu(OAc)
Ag CO
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
(2 equiv)
(2 equiv)
benzene
benzene
benzene
benzene
trace
trace
10
18
trace
93
72
no
no
trace
66
2
3
2
2
2
2
(10 mol %) oxone (2 equiv)
(10 mol %) (2 equiv)
(10 mol %) BuOO Bu (2 equiv) benzene
K
2
S
2
O
8
t
t
(10 mol %) Ag
2
2
2
2
CO
CO
CO
CO
3
3
3
3
(2 equiv)
(2 equiv)
(2 equiv)
(2 equiv)
benzene
benzene
benzene
benzene
CuCl
CuCO
2
(10 mol %)
(10 mol %)
Ag
Ag
3
Pd(OAc)
Pd(OAc)
2
2
(10 mol %) Ag
(10 mol %) Cu(OAc)
(10 mol %) Ag
(10 mol %) Ag
(10 mol %) Ag
(10 mol %) Ag
1
0
2
(2 equiv) benzene
1
1
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
2
2
2
2
2
CO
CO
CO
CO
3
3
3
3
(2 equiv)
toluence
xylene
acetonitrile 49
1,4-dioxane 75
1
1
1
1
2
3
4
5
(2 equiv)
(2 equiv)
(2 equiv)
80
Ag
2
CO
3
(10 mol %)
Cu(OAc)
2
(2 equiv) benzene
81
t
when oxone, K S O , BuOO Bu, and Ag CO respec-
t
2
2
8
2
3
tively were employed as oxidants in the presence of
Cu(OAc) (entries 3, 4, 5, 6), Ag CO was effective in
providing the desired product in 93% isolated yield, which
2
2
3
Initially, we selected the low-cost and readily available
quinoline N-oxide (1a) and hexanolactam (2a) as typical
was obviously superior to the others. CuCl was found to
2
promote the reaction (entry 7), although the yield was
inferior to that using Cu(OAc) , while CuCO was thor-
oughly invalid (entry 8). Pd(OAc) also displayed hardly
any catalytic performance (entries 9, 10). Among benzene,
toluene, xylene, acetonitrile, and 1,4-dioxane (entries 6, 11,
2
3
(
6) (a) Wang, X.-Q; Jin, Y.-H; Zhao, Y.-F; Zhu, L.; Fu, H. Org. Lett.
2
2
1
012, 14, 452. (b) Cho, S. H.; Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011,
33, 5996. (c) Shrestha, R.; Mukherjee, P.; Tan, Y.; Litman, Z. C.;
Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 8480. (d) Xiao, B.; Gong,
T.-J; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 1466. (e)
Thu, H. Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048.
12, 13, 14), benzene was the optimal solvent. The reaction
(
f) Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14058. (g) Inamoto,
proceeded in other solvents but gave a lower yield due
to the appearance of byproduct. When adding Ag CO
K.; Saito, T.; Katsuno, M.; Sakamoto, T.; Hiroya, K. Org. Lett. 2007, 9,
2
4
2
3
931. (h) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47,
52. (i) Jordan-Hore, J. A.; Johansson, C. C. C.; Gulias, M.; Beck, E. M.;
(10 mol %) and Cu(OAc) (2 equiv) into the system
2
Gaunt, M. J. J. Am. Chem. Soc. 2008, 130, 16184. (j) Tsang, W. C. P.;
Zheng, N.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 14560. (k)
Tsang, W. C. P.; Munday, R. H.; Brasche, G.; Zheng, N.; Buchwald,
S. L. J. Org. Chem. 2008, 73, 7603. (l) John, A.; Nicholas, K. M. J. Org.
Chem. 2011, 76, 4158. (m) Shuai, Q.; Deng, G.-J.; Chua, Z.-J.; Bohle,
D. S.; Li, C. J. Adv. Synth. Catal. 2010, 352, 632. (n) Monguchi, D.;
Fujiwara, T.; Furukawa, H.; Mori, A. Org. Lett. 2009, 11, 1607. (o)
Zhao, H.-Q.; Wang, M.; Su, W.-P.; Hong, M.-C. Adv. Synth. Catal.
(entry 15), the product was obtained in 81% isolated yield.
With the optimized conditions in hand, we set out to
explore the scope and generality of the dehydrogenative
amidation/amination of quinoline N-oxides with amides/
amines. Several quinoline N-oxide derivatives were em-
ployed as a coupling partner with hexanolactam as sum-
marized in Scheme 1. Quinoline N-oxide bearing an alkyl
(3ba, 3ca, 3da) and aryl (3ea) group in different positions
reacted smoothly to give the products in excellent yields.
Meanwhile, the good reactivity of 8-methyl-quinoline
N-oxide demonstrated that the reaction site is the
2
(
2
010, 352, 1301. (p) Wang, Q.; Schreiber, S. L. Org. Lett. 2009, 11, 5178.
q) Cho, S. H.; Kim, J. Y.; Lee, S. Y.; Chang, S. Angew. Chem., Int. Ed.
009, 48, 9127. (r) Li, Y.-M; Xie, Y.-S; Zhang, R.; Jin, K.; Wang, X.;
Duan, C.-Y. J. Org. Chem. 2011, 76, 5444. (s) Yin, J.-J.; Xiang, B.-P.;
Huffman, M. A.; Raab, C.-E.; Davies, I. W. J. Org. Chem. 2007, 72,
4
(
554. (t) Medley, J. W.; Movassaghi, M. J. Org. Chem. 2009, 74, 1341.
u) Manley, P. J.; Bilodeau, M. T. Org. Lett. 2002, 4, 3127. (v) Couturier,
M.; Caron, L.; Tumidajski, S.; Jones, K.; White, T. D. Org. Lett. 2006, 8,
1929. (w) Londregan, A. T.; Jennings, S.; Wei, L.-Q. Org. Lett. 2010, 12,
5
254.
(
(8) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130,
9245.
(9) Gong, X.; Song, G.-Y.; Zhang, H.; Li, X.-W. Org. Lett. 2011, 13,
1766.
7) (a) Wu, J.-L.; Cui, X.-L.; Chen, L.-M.; Jiang, G.-J.; Wu, Y.-J.
J. Am. Chem. Soc. 2009, 131, 13888. (b) Wu, Z.-Y.; Cui, X.-L.; Chen,
L.-M.; Jiang, G.-J.; Wu, Y.-J. Adv. Synth. Catal. 2013, 355, 1971.
B
Org. Lett., Vol. XX, No. XX, XXXX