Copper(I)- And gold(I)-catalyzed synthesis of 2,4-disubstituted quinoline derivatives from N-Aryl-2-propynylamines

Article abstract of DOI:10.1246/cl.2007.1422

2,4-Disubstituted quinoline derivatives were obtained from N-aryl-2-propynylamines catalyzed by copper(I) and gold(I) complexes. The quinoline derivatives could also be obtained by the reaction of N-arylaldimines with terminal acetylenes via the formation of N-aryl-2-propynylamines. Copyright

Full text of DOI:10.1246/cl.2007.1422

1422
Chemistry Letters Vol.36, No.12 (2007)
Copper(I)- and Gold(I)-catalyzed Synthesis of 2,4-Disubstituted
Quinoline Derivatives from N-Aryl-2-propynylamines
Yoichiro Kuninobu,Ã Yuichi Inoue, and Kazuhiko TakaiÃ
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, Tsushima, Okayama 700-8530
(Received September 18, 2007; CL-071035; E-mail: kuninobu@cc.okayama-u.ac.jp; ktakai@cc.okayama-u.ac.jp)
Table 1. Copper- and silver-catalyzed synthesis of quinolines
from 2-propynylamines
2,4-Disubstituted quinoline derivatives were obtained from
N-aryl-2-propynylamines catalyzed by copper(I) and gold(I)
complexes. The quinoline derivatives could also be obtained by
the reaction of N-arylaldimines with terminal acetylenes via the
formation of N-aryl-2-propynylamines.
R3
R3
Catalyst (5.0 mol %)
AgOTf (5.0 mol %)
3 (1.0 equiv.)
HN
R1
N
1,2-dichloroethane
80 °C, 24 h
R1
R2
R2
1
2
Yield/%a
CuCl
Quinoline derivatives are important as functional materials1
and medicines.2 There have been several classical methods for
the synthesis of quinolines; for example, Skraup,3 Doebner–von
Entry
1
Product (2)
Catalyst =
AuCl
Miller,4 Friedlander, Combes,5 and Ciamician–Dennstedt6 pro-
78 (81)
¨
1
2
HN
Ph
N
cedures. Recently, electrophilic cyclization using iodine,7 and
metal-mediated8 or -catalyzed9 syntheses of quinoline deriva-
tives have also been reported. We report herein the efficient syn-
thesis of 2,4-disubstituted quinoline derivatives from N-aryl-2-
propynylamines using the combination of copper(I)–silver or
gold(I)–silver as a catalyst, and an aldimine as a hydrogen accep-
tor. The copper(I)–silver system is also effective for the direct
formation of quinolines from aldimines and terminal acetylenes
in one-pot.
1b
2b
2c
95 (>99)
nBu
Ph
nBu
HN
nBu
73 (77)
19 (23)
3
4
1c
N
82 (86)
51 (56)
nBu
Ph
Ph
HN
5
6
N
1d
2d
nBu
nBu
nBu
nBu
OMe
Treatment of 2-propynylamine 1a with catalytic amounts of
copper(I) chloride and silver triflate in 1,2-dichloroethane at
80 ꢀC for 24 h gave quinoline derivative 2a in 38% yield
(eq 1).10–12 In this reaction, dihydrogen should be formed as
a side product. By adding an aldimine 3, which was derived from
benzaldehyde and aniline, as a hydrogen acceptor,13,14 the
yield of 2a increased dramatically and 2a was obtained in 93%
yield (eq 1).15
OMe
96 (>99)
68 (71)
35 (38)
7
8
HN
N
1e
2e
96 (>99)
42 (44)
18 (20)
Ph
Ph
Ph
Ph
CF3
CF3
9b
10b
HN
Ph
N
N
1f
2f
CuCl (5.0 mol %)
Ph
Ph
Ph
Ph
AgOTf (5.0 mol %)
additive (1.0 equiv.)
Additive 2a
HN
Ph
N
(1)
38%
93%
11c
12d
HN
Ph
Ph
Ph
1g
CO2Et
2g
CO2Et
1,2-dichloroethane
3
1a
2a
Ph
80 °C, 24 h
By using a mixture of copper(I) chloride and silver triflate as
aIsolated yield. 1H NMR yield is reported in parentheses.
a catalyst, 2-propynylamine bearing an alkyl group at either a
terminal position of the acetylene moiety or the propargyl po-
sition, 1b and 1c, gave quinoline derivatives 2b and 2c in 78%
and 73% yields, respectively (Table 1, Entries 1 and 3). The
yields of quinoline derivatives increased when a combination
of gold(I) chloride and silver triflate was used; 2b and 2c were
obtained in 95% and 82% yields, respectively (Table 1, Entries
2 and 4). A 2-propynylamine possessing possessing alkyl groups
at both a terminal position of the acetylene moiety and the prop-
argyl position, 1d, provided quinoline derivative 2d in 19%
and 51% yields, respectively (Table 1, Entries 5 and 6). With a
2-propynylamine having an electron-donating group at the para-
position of the phenyl group on the nitrogen atom, 1e, quinoline
delivative 2e was formed quantitatively (Table 1, Entries 7 and
8). On the other hand, a 2-propynylamine bearing an electron-
withdrawing group, 1f, provided quinoline derivative 2f in
b100 ꢀC. CuCl (10 mol %), AgOTf (10 mol %), 100 ꢀC. AuCl
c
d
(10 mol %), AgOTf (10 mol %), 100 ꢀC.
68% and 42% yields, respectively (Table 1, Entries 9 and
10).16 The formation of quinoline derivative 2f in moderate yield
deserves special mention since it is usually difficult to carry out
hydroarylation of acetylenes with aromatic compounds bearing
electron-withdrawing group(s). A 2-propynylamine with an ester
moiety at the terminal position of the acetylene moiety 1g also
produced the corresponding quinoline derivative 2g, however
the yield was low (Table 1, Entries 11 and 12).
We consider the proposed mechanism as follows: (1) forma-
tion of copper(I) or gold(I) cation by the reaction of copper(I)
chloride or gold(I) chloride with silver triflate; (2) coordination
of a 2-propynylamine to the metal center. After this reaction
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.12 (2007)
1423
the other hand, in the latter reactions, the combination of
copper(I) chloride and silver triflate showed a higher efficiency
than that of gold(I) chloride and silver triflate.
HN
Ph
M+
N
Ph
Ph
Ph
References and Notes
+
M+
H
N
HN
H
HN
Ph
1
a) C. W. Tang, S. A. Van Slyke, Appl. Phys. Lett. 1987, 51, 913. b) J. I.
Kim, I. S. Shin, H. Kim, J.-K. Lee, J. Am. Chem. Soc. 2005, 127, 1614.
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Jones, D. K. Herron, J. W. Lampe, J. R. McCowan, W. T. McMillen,
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Lett. 2003, 13, 4355. c) P. G. Bray, S. A. Ward, P. M. O’Neill, Curr.
Top. Microbiol. 2005, 295, 3.
H
M
Ph
Ph
Ph
Ph
(4-a)
(3-a)
(4-b)
(5-a)
Ph
H
M
Ph
2
M+
Ph
+
Ph
N
HN
HN
(3-b)
Ph
H
Ph
Ph
H
(6-b)
(5-b)
+
H
N
HN
HN
Ph
H
Ph
M
M+
Ph
Ph
Ph
Ph
H
H
M
M+
H
3
4
5
6
F. Tiemann, J. Oppermann, Ber. Dtsch. Chem. Ges. 1880, 13, 2056.
O. Doebner, W. von Miller, Ber. Dtsch. Chem. Ges. 1881, 14, 2812.
A. Combes, Bull. Soc. Chim. Fr. 1883, 49, 89.
G. L. Ciamician, M. Dennstedt, Ber. Dtsch. Chem. Ges. 1881, 14,
1153.
X. Zhang, M. A. Campo, T. Yao, R. C. Larock, Org. Lett. 2005, 7,
763.
For a zinc(II)-mediated reaction, see: B. Jiang, Y.-G. Si, J. Org.
Chem. 2002, 67, 9449.
a) M. Beller, O. R. Thiel, H. Trauthwein, C. G. Hartung, Chem.—Eur.
J. 2000, 6, 2513. b) H. Z. Syeda Huma, R. Halder, S. S. Kalra, J. Das,
J. Iqbal, Tetrahedron Lett. 2002, 43, 6485. c) J. Jacob, W. D. Jones,
J. Org. Chem. 2003, 68, 3563. d) D. K. O’Dell, K. M. Nicholas, J.
Org. Chem. 2003, 68, 6427. e) G. Abbiati, A. Arcadi, F. Marinelli,
E. Rossi, M. Verdecchia, Synlett 2006, 3218. f) R. P. Korivi, C.-H.
Cheng, J. Org. Chem. 2006, 71, 7079. g) T. Nakajima, T. Inada, T.
Igarashi, T. Sekioka, I. Shimizu, Bull. Chem. Soc. Jpn. 2006, 79,
1941. h) A. W. Sromek, A. L. Rheingold, D. J. Wink, V. Gevorgyan,
Synlett 2006, 2325. i) M. Movassaghi, M. D. Hill, J. Am. Chem. Soc.
2006, 128, 4592.
Scheme 1. Proposed mechanism for the formation of quinoline
derivatives.
step, there are two possible pathways. Path A: (3-a) cyclization;
(4-a) deprotonation and rearrangement of the metal center; (5-a)
dehydride and elimination of the metal center. Path B: (3-b)
isomerization of the 2-propynylamine to an arenylamine; (4-b)
cyclization; (5-b) deprotonation and rearrangement of the metal
center; (6-b) dehydridation and elimination of the metal center
(Scheme 1).
Quinoline derivatives could also be synthesized by the
reactions of aldimines with terminal acetylenes (eq 2). Treat-
ment of an aromatic aldimine 3 with phenylacetylene (4a) in
the presence of copper(I) chloride and silver triflate gave quino-
line derivative 2a in 91% yield (eq 2).17,18 Alkylacetylene 4b
also reacted with aldimine 3, and gave the corresponding
quinoline 2b in 84% yield (eq 2).
7
8
9
10 Results for other catalysts are as follows: CuCl, 15%; AgOTf, 90%;
CuCl2, 10%; Cu(OTf)2, 92%; CuCl + In(OTf)3, 94%; CuCl2
+
CuCl (X mol %)
N
AgOTf (X mol %)
N
HN
Ph
In(OTf)3, 81%; In(OTf)3, 10%; AuCl + AgOTf, 99%; AuCl, 32%;
AuCl3 + AgOTf, 98%; AuCl3, 17%; GaCl3, 20%; InCl3, 18%; PtCl2,
39%.
+
+
Ph
H
3
Ph
R
R
1,2-dichloroethane
100 °C, 24 h
1
4
2
(2)
R
(2.0 equiv.)
(1.0 equiv.)
11 Copper-catalyzed synthesis of quinoline derivatives has already been
reported. However, the yield of quinolines and efficiency were low.
See: ref. 9b.
12 In this reaction, 1,2-dihydroquinoline was not detected.
13 Results for other acceptors are as follows: norbornene, 39%; 3,3-
dimethyl-1-butene, 46%; 3-pentanone, 18%; acetophenone, 43%;
nonanal, 58%; benzaldehyde, 59%.
14 When O2 or aq. H2O2 was used as an oxidant, the yield of 2a could not
be improved.
15 Benzylphenylamine was obtained in 91% yield.
16 Only a trace amount of quinoline 2f was formed in the absence of
AgOTf.
17 There have been some reports on copper(I)-catalyzed synthesis of
2-propynylamines from aldimines and terminal acetylenes. See: a)
C. Wei, C.-J. Li, J. Am. Chem. Soc. 2002, 124, 5638. b) J. N. Rosa,
A. Gil Santos, C. A. M. Afonso, J. Mol. Catal. A: Chem. 2004, 214,
161. c) M. Benaglia, D. Negri, G. Dell’Anna, Tetrahedron Lett.
2004, 45, 8705.
18 The combination of gold(I) chloride and silver triflate, which has high
ability to catalyze the formation of quinoline 2a from 2-propynyl-
amine 1a, showed low ability to catalyze the formation of quinoline
2a (41%) by the reaction of aldimine 3 with phenylacetylene (4a).
This result shows that the combination of gold(I) chloride and silver
triflate is not effective for the formation of 2-propynylamine 1a from
aldimine 3 and phenylacetylene (4a). Results for other catalysts are as
follows: Cu(OTf)2, 82%; AgOTf, 61%; CuCl + In(OTf)3, 91%.
19 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.
X / mol %
Yield/%
R
91 (2a) 3 (1a)
84 (2b) <1 (1b)
Ph
5
nBu
10
One-pot three-component coupling of benzaldehyde (5),
aniline (6), and phenylacetylene (4a) also provided quinoline
2a in 92% yield (eq 3).
CuCl (10 mol %)
AgOTf (10 mol %)
4a (1.0 equiv.)
O
+
Ph
H
H2N
1,2-dichloroethane 1,2-dichloroethane
25 °C, 20 min 100 °C, 24 h
5
6
(2.1 equiv.) (2.1 equiv.)
(3)
HN
Ph
N
+
Ph
Ph
2a
92%
1a
<1%
Ph
In summary, we have succeeded in copper(I)- and gold(I)-
catalyzed synthesis of 2,4-disubstituted quinoline derivatives
from N-aryl-2-propynylamines. The quinoline derivatives could
also be obtained by the reaction of N-arylaldimines with terminal
acetylenes via the formation of N-aryl-2-propynylamines. In
the former reactions, the combination of gold(I) chloride and
silver triflate was better able to give quinoline derivatives. On
Published on the web (Advance View) November 3, 2007; doi:10.1246/cl.2007.1422