Sequential catalytic process: synthesis of quinoline derivatives by AuCl3/CuBr-catalyzed three-component reaction of aldehydes, amines, and alkynes

Article abstract of DOI:10.1016/j.tet.2008.01.046

A sequential catalytic process has been developed based on gold-catalyzed nucleophilic addition of terminal alkynes to imines, and gold-catalyzed intramolecular reaction of aromatic ring to alkynes. This one-pot reaction of aldehydes, amines, and alkynes gives quinoline derivatives in good yields.

Full text of DOI:10.1016/j.tet.2008.01.046

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2755e2761
www.elsevier.com/locate/tet
Sequential catalytic process: synthesis of quinoline derivatives by
AuCl3/CuBr-catalyzed three-component reaction of
aldehydes, amines, and alkynes
*
Fengping Xiao, Yulin Chen, Yu Liu, Jianbo Wang
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China
Received 8 October 2007; received in revised form 5 January 2008; accepted 11 January 2008
Available online 16 January 2008
Dedicated to Professor Hiroshi Suginome on the occasion of his 77th birthday
Abstract
A sequential catalytic process has been developed based on gold-catalyzed nucleophilic addition of terminal alkynes to imines, and
gold-catalyzed intramolecular reaction of aromatic ring to alkynes. This one-pot reaction of aldehydes, amines, and alkynes gives quinoline
derivatives in good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Catalysis; Gold; Quinoline; Propargyl amine; Alkyne; Nucleophilic addition
1. Introduction
demonstrated a highly efficient three-component coupling reac-
tion of aldehydes, alkynes, and amines via CeH activation cata-
lyzed by gold in water. The reaction affords propargyl amines in
high yields.12 On the other hand, the use of single catalytic sys-
tem to mediate two or more transformations in a single synthetic
operation has recently emerged as a new research area.13 This
strategy is efficient to build complex structures from simple
starting materials in an environmentally compatible fashion. In-
spired by these developments, we have conceived that it might
be possible to combine the Au-catalyzed addition of terminal
Gold has attracted more and more attentions in chemistry.1
Generally, AuI and AuIII act as soft Lewis acids, and they pref-
erentially coordinate with soft Lewis bases, such as alkynes
and allenes. The activated alkynes or allenes become susceptible
to be attacked by various nucleophiles, such as alcohols/water,2
nitrogen,3 carbon nucleophiles,4 carboxylic acids,5 ketones,6
and thiols.7 Among the carbon nucleophiles, aromatic rings
have unique properties and have received attentions recently.8
For example, Nevado and Echavarren have recently demon-
strated AuI-catalyzed intramolecular hydroarylation of alkyne
by electron rich aromatic moiety.8c
On the other hand, it has been reported that transition metal
complexes, such as silver,9 ruthenium,10 and copper,11 can cata-
lyze the addition of terminal alkynes to imines to afford prop-
argyl amine derivatives. A recent interesting development in
this field has been reported by Wei and Li, who have
NH2
R'
O
R"
MLn
HN
+
+ R'
H
R
R
R"
R'
HN
MLn
products
R
R"
LnM
* Corresponding author. Fax: þ86 10 6275 1708.
E-mail address: wangjb@pku.edu.cn (J. Wang).
Scheme 1. A sequential catalytic process.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.046

2756
F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
Table 1
Optimization of reaction conditions for acid-catalyzed of 4a
alkynes to imines and the Au-catalyzed reaction of alkynes in
a one-pot sequential catalytic process (Scheme 1). Herein, we
report a novel method to synthesize quinoline derivatives by
the AuCl3/CuBr-catalyzed three-component reaction of alde-
hydes, amines, and alkynes.
HN
catalyst
5 mol %
N
Ph
Ph
4a
5a
2. Results and discussions
Entry Catalyst
Solvent Temperature (ꢀC) Time
Yielda (%)
On the outset of this investigation, we have examined the
three-component reaction of benzaldehyde, aniline, and phe-
nylacetylene with AuCl3 as a catalyst (Scheme 2). The reac-
tion afforded two products. One was the addition product
4a, which was formed by nucleophilic addition of the terminal
alkyne to the imine that was generated in situ. The other prod-
uct was a quinoline derivative 5a. The formation of 5a sug-
gested the further transformation of the addition product 4a
by Au catalysis under this reaction condition was indeed pos-
sible. This result prompted us to examine the Au-catalyzed
reaction of propargyl amine 4a in detail.
1
AuCl3þ3AgOTf DCE
80
AuCl3þ3AgOTf PhCH3 110
24 h
14 h
12 h
38
66
48
2
3
AuClþAgOTf
PhCH3 110
4
AuCl3þ3AgOTf MeOH 120b
10 min 71
4 days 71
4 days 85
8 days 83
15 min 68
5
AuCl3þ3AgOTf MeOH
25
25
15
6
AuCl3
AuCl
MeOH
MeOH
7
8
AuCl3
PtCl2
MeOH 120b
PhCH3 110
9
27 h
2 days dc
8 h
dd
8 days dc
8 days dc
10 days dc
10 days dc
44
10
11
12
13
14
15
a
TfOH
TfOH
TsOH
HCl
PhCH3
PhCH3
PhCH3
MeOH
MeOH
MeOH
25
80
25
25
25
25
CuBr
No catalyst
O
NH2
Ph
AuCl3
H
Yields after column chromatographic purification with silica gel.
Reaction was carried out under microwave irradiation.
Compound 5a was not detected and 4a was recovered.
A complex mixture was obtained.
+
+
b
c
3a
2a
1a
d
HN
affect the reaction. Substrates bearing functional groups such as
allyloxy and bromide (Table 2, entries 3, 4, 7, 8, and 10) were
tolerated. This made possible the further derivatization of the
quinoline products. However, R2 and R3 were found to
N
+
Ph
Ph
5a
4a
Scheme 2. AuCl3-catalyzed three-component reaction of aldehydes 1a, amine
2a, and terminal alkyne 3a.
Table 2
AuCl3-catalyzed propargyl amines 4aeo
AuCl and AuCl3 were examined as catalysts for the reaction
of propargyl amine 4a under various conditions (Table 1). Both
catalysts worked well to give 5a in good yields. Reaction with
AuCl3 as catalyst gave better results. Addition of AgOTf did
not improve the yield. Microwave or higher reaction tempera-
ture could significantly shorten the reaction time, but the yields
were not improved (entries 1e5). PtCl2 was also examined as
a catalyst, but it gave 5a in low yield (entry 9). The optimized
reaction condition was to use AuCl3 in MeOH at room temper-
ature (entry 6). Under this condition the reaction gave the quin-
oline product 5a in good yield, although the reaction took
a long time (4 days). It was worthwhile to note that protonic
acids failed to catalyze the reaction (entries 10e14).14 Finally,
control experiment indicated that no reaction occurred in the
absence of a catalyst.
Subsequently, a series of propargyl amines 4beo were pre-
pared according to the method developed by Li and co-workers,
who used a combination of RuCl3 and CuBr as catalyst.10 These
propargyl amines were subjected to the optimized reaction con-
ditions with AuCl3 catalyst in MeOH. As shown in Table 2, for
most substrates the reaction provided good yields of quinoline
derivatives, although in general the reaction required a long
time. It was noted that the substituents R1 did not significantly
R2
R2
AuCl3
HN
(5 mol %)
N
MeOH, r.t.
R3
R1
R1
R3
4a-o
5a-o
Entry Substrate (4aeo)
Product Time Yielda (%)
(5aeo) (days)
1
4a, R1¼R2¼H; R3¼Ph
5a
5b
5c
4
85
79
86
86
72
65
87
86
85
74
83
72
74
0
2
4b, R1¼H; R2¼CH3; R3¼Ph
2
3
4c, R1¼2-allyloxy; R2¼H; R3¼Ph
3
4
4d, R1¼2-allyloxy; R2¼CH3; R3¼Ph 5d
3
5
4e, R1¼2-Me; R2¼H; R3¼Ph
4f, R1¼2-Me; R2¼CH3; R3¼Ph
4g, R1¼3-Br; R2¼H; R3¼Ph
4h, R1¼3-Br; R2¼CH3; R3¼Ph
4i, R1¼3-OMe; R2¼H; R3¼Ph
4j, R1¼4-Br; R2¼H; R3¼Ph
4k, R1¼4-Cl, R2¼H; R3¼Ph
4l, R1¼4-Ph; R2¼H; R3¼Ph
4m, R1¼H; R2¼H; R3¼1-naphthyl
4n, R1¼H; R2¼4-BrC6H4; R3¼H
5e
5f
4
6
1.5
5
7
5g
5h
5i
8
1.5
4
9
10
11
12
13
14
15
a
5j
2.5
2.5
4
5k
5l
5m
5n
4
2
4o, R1¼H; R2¼H; R3¼CH2CH2OTHP 5o
3
0
Yields after column chromatographic purification with silica gel.

F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
2757
markedly affect the reaction. R3 could be phenyl or naphthyl.
Table 4
Sequential catalytic process with AuCl3/CuBr
When R2 was an aryl group bearing an electron-withdrawing
group, such as 4-bromophenyl, the reaction didn’t proceed
even in refluxing MeOH (entry 14). When R3 was an alkyl
group, no desired product was obtained (entry 15).
O
NH2
H
R1
R3
+
+
R2
In the preparation of propargyl amines 4aeo, we have fol-
lowed Li’s approach, which is a RuCl3/CuBr-catalyzed three-
component reaction of aldehyde, amine, and alkyne.10 We
have found that it is not necessary to purify the propargyl
amine products for the subsequent AuCl3-catalyzed reaction.
The AuCl3-catalyzed reaction can be successfully carried out
by simple extraction or filtration of the reaction mixture, fol-
lowed by addition of AuCl3 and MeOH. As shown by the
data collected in Table 3, the quinoline products could be
isolated in good to excellent yields in this way.
1
2
3
R2
AuCl
CuBr (30 mol %)
3 (5 mol%)
N
R3
R1
MeOH
5a-m
Entry R1, R2, R3
Product Time (days) Yielda (%)
1
R1¼R2¼H; R3¼Ph
5a
5b
5c
12
7
8
7
4
4
5
7
7
7
7
7
6
55
67
62
73
64
77
65
87
52
84
86
48
69
2
R1¼H; R2¼CH3; R3¼Ph
3
R1¼2-allyloxy; R2¼H; R3¼Ph
4
R1¼2-allyloxy; R2¼CH3; R3¼Ph 5d
Table 3
Sequential catalytic process with two catalytic system
5
R1¼2-Me; R2¼H; R3¼Ph
R1¼2-Me; R2¼CH3; R3¼Ph
R1¼3-Br; R2¼H; R3¼Ph
R1¼3-Br; R2¼CH3; R3¼Ph
R1¼3-OMe; R2¼H; R3¼Ph
R1¼4-Br; R2¼H; R3¼Ph
R1¼4-Cl, R2¼H; R3¼Ph
R1¼4-Ph; R2¼H; R3¼Ph
R1¼H; R2¼H; R3¼1-naphthyl
5e
5f
6
O
7
5g
5h
5i
NH2
8
H
R1
R3
N
+
+
9
R2
10
11
12
13
a
5j
3
1
2
5k
5l
R2
[10]
5m
cat. RuCl3
cat. CuBr
AuCl3
(5 mol%)
Yields after column chromatographic purification with silica gel.
R3
H2O or neat
MeOH
R1
A mechanism for the formation of the quinoline derivatives
5c, d, f, g, h
Product Timea (days) Yieldb (%)
is proposed in Scheme 3. The triple bond of 4a could be acti-
vated by AuCl3 to promote an intramolecular nucleophilic at-
tack by the N-substituted phenyl ring attached to the nitrogen.
The dihydroquinoline intermediate 8 could be further oxidized
by air O2 to afford quinoline product 5a.
Entry R1, R2, R3
3
4
6
7
8
R1¼2-allyloxy; R2¼H; R3¼Ph
5c
7.5
5.5
6.5
2.5
2.5
76
94
55
65
80
R1¼2-allyloxy; R2¼CH3; R3¼Ph 5d
R1¼2-Me; R2¼CH3; R3¼Ph
R1¼3-Br; R2¼H; R3¼Ph
R1¼3-Br; R2¼CH3; R3¼Ph
5f
5g
5h
a
The total reaction time for two steps.
Yields after column chromatographic purification with silica gel.
b
HN
AuCl3
4a
Ph
Since Li and co-workers have previously reported the gold-
Cl3Au
6
catalyzed three-component reaction of aldehydes, alkynes, and
amines to provide propargyl amines,12 we further conceived
that a sequential AuCl3-catalyzed reaction of aldehydes, al-
kynes, and amines to generate quinoline derivatives might be
possible. As shown by the results in Scheme 2, the initial ex-
periment suggested that quinoline derivative was formed by
the AuCl3-catalyzed three-component reaction, but the reac-
tion proceeded very slowly. Inspired by Li’s catalytic system
with RuCl3/CuBr in the preparation of propargyl amine, we
introduced CuBr as co-catalyst in the AuCl3-catalyzed three-
component reaction. It was then found that the yield of the
reaction could be improved by adding 30 mol % CuBr, al-
though the reaction time remained essentially the same. As
shown in Table 4, a series of quinoline derivates were obtained
in moderate to good yields in this three-component reaction
catalyzed by AuCl3/CuBr. We suggest that the role of CuBr
is to activate the imine intermediate, which is attacked by
gold alkynilide.
HN
N
Ph
Ph
AuCl3
Au
7
8
AuCl3 O2
5a
Scheme 3. Mechanistic proposal.
Although it is known that dihydroquinoline can be easily
oxidized,15 we wondered if AuCl3 had effect on the oxidation.
Thus, 1,2-dihydroquinoline 9 was prepared through the reduc-
tion of quinoline with LiAlH4.16 Stirring 1,2-dihydroquinoline
9 with 5 mol % AuCl3 in MeOH afforded quinoline 10 in 90%
yield within 1 h (Scheme 4), while in the absence of AuCl3 the
oxidation proceeded very slowly.

2758
F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
AuCl3
(5 mol %)
O
NH2
TfOH
26%
N
H
MeOH, r.t.
Air, 1 h
90%
N
H
N
+
+
Ph
Ph
9
10
5a
Scheme 4. Oxidation of 1,2-dihydroquinoline.
O
NH2
H
N
The AuCl3-catalyzed reaction of 4k was further carried out
under the condition in which oxygen was strictly excluded. As
H
H
+
1
expected, dihydroquinoline 11 was observed in the crude H
Ph
NMR. Due to its rapid oxidation in the workup, a mixture of di-
hydroquinoline 11 and quinoline derivative 5k was isolated in
67% yield with 3:1 ratio (Scheme 5). It was noted that 11 was
completely converted to 5k when keeping in CDCl3 for 2 days.
H
HN
N
H
Ph
Ph
H
12
AuCl3
(5 mol %)
HN
[O]
HN
5a
MeOH, rt
N2
4d, 67%
Ph
Cl
4k
Scheme 6. TfOH-catalyzed three-component reaction.
N
HN
4. Experimental section
4.1. General information
+
Cl
:
Cl
5k
11
3
1
For chromatography, 200e300 mesh silica gel (Qingdao,
China) was employed. 1H and 13C NMR spectra were recorded
at 200 and 50 MHz with a Varian Mercury 200 spectrometer,
or 300 and 75 MHz with a Varian Mercury 300 spectrometer.
Chemical shifts are reported in parts per million using tetra-
methylsilane (TMS) as internal standard. Mass spectra were
obtained on a VG ZAB-HS mass spectrometer. The Au cata-
lysts, RuCl3 hydrate and CuBr are commercially available
and are used without further purification.
Scheme 5. AuCl3-catalyzed reaction of 4k under N2 atmosphere.
To optimize the acid-catalyzed reaction of 4a, several protic
acids, such as TsOH, TfOH, and HCl, were tested but did not
catalyze the reaction (Table 1, entries 10e13). This could be
rationalized by the fact that proton as hard acid preferentially
interacts with amino nitrogen, while AuI or AuIII as soft Lewis
acid favorably coordinates with triple bond.
4.2. General procedure for the preparation of propargyl
amines 4aem10
H
HN
N
H
A mixture of aldehyde (2 mmol) and aniline (2.4 mmol) was
heated at 60 ꢀC for about 2 h. Then RuCl3 (3 mol %), CuBr
(30 mol %), phenylacetylene (1.2 mmol), and water (2 mL) or
solvent free were added into the mixture under N2. The mixture
was stirred at room temperature for 10 min and at 40 ꢀC over-
night. The reaction mixturewas poured intowater, and extracted
with diethyl ether (or methylene chloride). The organic layer
was washed with water and dried over anhydrous MgSO4. The
solvent was removed in vacuo. The product was isolated by col-
umn chromatography on silica gel eluting with EtOAcehexane.
Cl3Au
Interestingly, TfOH-catalyzed three-component reaction
gave 5a in 26% isolated yield (Scheme 6). This result could
be rationalized as follows. In TfOH-catalyzed three-compo-
nent reaction, the formation of 5a might not be through 4a,
rather it formed through a vinylic cation intermediate.17
3. Conclusion
In conclusion, we have developed a simple and effective cata-
lytic method to form quinoline derivatives by using a AuCl3-cata-
lyzed reaction of propargyl amines, or by a AuCl3/CuBr-catalyzed
three-component reaction of aldehydes, amines, and alkynes.
These processes can provide a diverse range of quinoline deriva-
tives in moderate to good yields from simple starting materials.
4.3. General procedure for the preparation of quinoline
derivatives 5aem from propargyl amines
To a solution of propargyl amine (0.5 mmol) in anhydrous
MeOH (5 mL) at room temperature under air was added
AuCl3 (5 mol %). After being stirred at room temperature

F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
2759
for enough time, the starting material disappeared as judged by
TLC. The solvent was removed by evaporation under reduced
pressure and the crude product was purified by chromatogra-
phy to afford quinoline derivatives.
128.09, 128.39, 128.46, 129.10, 129.52, 131.67, 133.01,
144.49, 155.64; EIMS (m/z, relative intensity): 353 (Mþ, 21),
312 (6), 247 (100), 232 (7), 205 (10), 178 (14), 141 (27), 115
(12); HRMS calcd for C25H23ON: 353.1780; found: 353.1772.
4.4. General procedure for the preparation of quinoline
derivatives 5aem from three-component material
4.4.4. 2-[2-(Allyloxy)phenyl]-6-methyl-4-phenylquinoline
(5d)
IR (film): 684, 701, 753, 827, 1274, 1423, 1491, 1547, 1587,
1
First, a mixture of aldehyde (1 mmol) and aniline (1.2 mmol)
was heated at 60 ꢀC for about 2 h. Then AuCl3 (5 mol %), CuBr
(30 mol %), phenylacetylene (1.2 mmol), and MeOH (1 mL)
were added into the mixture under N2. The mixture was stirred
at room temperature for 10 min then at 40 ꢀC overnight. Then
the mixture was stirred at room temperature for enough time
when TLC showed that the reaction had completed. The solvent
was removed by evaporation under reduced pressure and the
crude product was purified by chromatography to yield quino-
line derivative.
1600; H NMR (300 MHz, CDCl3) d 2.46 (s, 3H), 4.56 (dd,
J¼1.5, 3.3 Hz, 2H), 5.15e5.34 (m, 2H), 5.91e6.02 (m, 1H),
6.99 (d, J¼8.1 Hz, 1H), 7.13 (dt, J¼0.6, 7.5 Hz, 1H), 7.34e7.55
(m, 7H), 7.67 (s, 1H), 7.86 (s, 1H), 7.91 (dd, J¼1.5, 7.5 Hz, 1H),
8.14 (d, J¼8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 21.67,
69.23, 112.93, 117.07, 121.50, 123.88, 124.25, 125.46, 128.00,
128.39, 129.53, 129.66, 130.06, 131.45, 132.99, 136.05, 138.67,
146.55, 147.27, 155.56, 156.17; EIMS (m/z, relative intensity):
351 (Mþ, 66), 336 (24), 322 (35), 310 (44), 294 (73), 280 (55),
267 (13), 202 (6), 189 (8), 165 (4), 139 (4); HRMS calcd for
C25H21ON: 351.1623; found: 351.1618.
4.4.1. N-{1-[2-(Allyloxy)phenyl]-3-phenylprop-2-ynyl}-
benzenamine (4c)
4.4.5. N-[3-Phenyl-1-(o-tolyl)prop-2-ynyl]benzenamine (4e)
IR (film): 690, 723, 1501, 1601; 1H NMR (300 MHz, CDCl3)
d 2.45 (s, 3H), 4.01 (s, 1H), 5.56 (d, J¼4.8 Hz, 1H), 6.73e6.80
(m, 3H), 7.18e7.77 (m, 10H), 7.78e7.80 (m, 1H); 13C NMR
(75 MHz, CDCl3) d 18.95, 48.12, 84.73, 88.30, 113.75,
118.39, 122.83, 126.42, 127.17, 128.15, 128.18, 128.21,
129.18, 130.83, 131.71, 136.16, 137.42, 146.65; EIMS (m/z, rel-
ative intensity): 297 (Mþ, 10), 205 (100), 190 (6), 127 (5);
HRMS calcd for C22H19N: 297.1518; found: 297.1512.
IR (film): 691, 751, 1245, 1490, 1501, 1601; 1H NMR
(300 MHz, CDCl3) d 4.35 (s, 1H), 4.58e4.63 (m, 2H), 5.21e
5.26 (m, 1H), 5.39e5.46 (m, 1H), 5.83 (s, 1H), 5.96e6.08 (m,
1H), 6.73e6.80 (m, 3H), 6.89 (d, J¼7.5 Hz, 1H), 6.98 (dt,
J¼7.8, 1.2 Hz, 1H), 7.15e7.41 (m, 8H), 7.66 (dd, J¼1.5,
7.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 45.82, 68.87,
83.55, 89.02, 112.32, 114.17, 117.14, 118.30, 121.04, 123.01,
128.00, 128.08, 128.20, 128.41, 128.99, 129.14, 131.64,
131.94, 146.75, 155.60; EIMS (m/z, relative intensity): 339
(Mþ, 11), 298 (8), 247 (100), 232 (6), 205 (17), 178 (17), 165
(5), 152 (9), 141(29), 115 (13), 103 (11); HRMS calcd for
C24H21ON: 339.1623; found: 339.1620.
4.4.6. 4-Phenyl-2-(o-tolyl)quinoline (5e)
IR (film): 701, 728, 766, 1355, 1406, 1444, 1489, 1574, 1547,
1
1590; H NMR (300 MHz, CDCl3) d 2.45 (s, 3H), 7.27e7.30
(m, 3H), 7.45e7.54 (m, 8H), 7.68e7.74 (m, 1H), 7.93 (d,
J¼8.1 Hz, 1H), 8.21 (d, J¼8.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 20.40, 122.53, 125.21, 125.58, 125.97, 126.39,
128.36, 128.47, 128.54, 129.41, 129.56, 129.72, 129.99, 130.85,
136.00, 138.11, 140.60, 148.38, 159.80; EIMS (m/z, relative in-
tensity): 295 (Mþ, 64), 294 (100), 218 (78), 133 (3); HRMS
calcd for C22H17N: 295.1361; found: 295.1359.
4.4.2. 2-[2-(Allyloxy)phenyl]-4-phenylquinoline (5c)
IR (film): 702, 754, 763, 1239, 1277, 1356, 1449, 1546, 1590;
1H NMR (300 MHz, CDCl3) d 4.58 (dt, J¼4.8, 1.8 Hz, 2H),
5.15e5.20 (m, 1H), 5.28e5.36 (m, 1H), 5.92e6.04 (m, 1H),
6.70e7.02 (m, 1H), 7.14 (dt, J¼7.5, 0.9 Hz, 1H), 7.36e7.57
(m, 7H), 7.68e7.13 (m, 1H), 7.90e7.93 (m, 3H), 8.23e8.26
(m, 1H); 13C NMR (75 MHz, CDCl3) d 69.28, 112.97, 117.17,
121.56, 123.86, 125.53, 125.57, 126.17, 128.13, 128.43, 129.02,
129.59, 130.00, 130.06, 130.23, 131.53, 133.01, 138.50, 147.23,
148.79, 156.24, 156.58; EIMS (m/z, relative intensity): 337
(Mþ, 49), 322 (18), 308 (32), 296 (27), 280 (100), 267 (18), 241
(5), 202 (9), 176 (7); HRMS calcd for C24H19ON: 337.1467;
found: 337.1460.
4.4.7. 4-Methyl-N-[3-phenyl-1-(o-tolyl)prop-2-ynyl]
benzenamine (4f)
IR (film): 691, 756, 807, 1489, 1518, 1616, 2919, 3020, 3406;
1H NMR (300 MHz, CDCl3) d 2.31 (s, 3H), 2.51 (s, 3H), 3.94 (s,
1H), 5.59 (s, 1H), 6.73 (d, J¼7.8 Hz, 2H), 7.08 (d, J¼7.8 Hz,
2H), 7.25e7.48 (m, 8H), 7.83e7.86 (m, 1H); 13C NMR
(75 MHz, CDCl3) d 18.93, 20.44, 48.33, 84.64, 88.50, 113.89,
122.87, 126.34, 127.13, 127.58, 128.07, 128.15, 129.66,
130.77, 131.70, 136.15, 137.55, 144.36; EIMS (m/z, relative in-
tensity): 311 (Mþ, 12), 205 (100), 190 (6), 178 (5), 127 (5), 107
(4); HRMS calcd for C23H21N: 311.1674; found: 311.1673.
4.4.3. N-{1-[2-(Allyloxy)phenyl]-3-phenylprop-2-ynyl}-4-
methylbenzenamine (4d)
IR (film): 692, 754, 808, 1244, 1490, 1518, 3020, 3405; 1H
NMR (300 MHz, CDCl3) d 2.22 (s, 3H), 4.23 (s, 1H), 4.59e
4.66 (m, 2H), 5.22e5.26 (m, 1H), 5.40e5.47 (m, 1H), 5.77 (s,
1H), 5.97e6.10 (m, 1H), 6.69e6.72 (m, 2H), 6.88e7.00 (m,
4H), 7.19e7.40 (m, 6H), 7.64 (dd, J¼1.8, 7.5 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 20.44, 46.24, 68.92, 83.54, 89.24,
112.32, 114.54, 117.19, 121.06, 123.11, 127.60, 127.99,
4.4.8. 6-Methyl-4-phenyl-2-(o-tolyl)quinoline (5f)
IR (film): 701, 728, 756, 828, 1353, 1489, 1574, 1588, 2921,
3057; 1H NMR (300 MHz, CDCl3) d 2.46 (s, 3H), 2.48 (s, 3H),
7.30e7.71 (m, 12H), 8.13 (d, J¼8.4 Hz, 1H); 13C NMR

2760
F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
(75 MHz, CDCl3) d 20.39, 21.79, 122.59, 124.30, 125.15,
125.93, 128.24, 128.35, 128.53, 129.53, 129.70, 130.80, 131.63,
135.99, 136.31, 138.34, 140.68, 146.96, 147.66, 158.85; EIMS
(m/z, relative intensity): 309 (Mþ, 72), 308 (100), 292 (6), 232
(76), 217 (9); HRMS calcd for C23H19N: 309.1518; found:
309.1529.
4.4.13. 2-(3-Methoxyphenyl)-4-phenylquinoline (5i)
IR(film):701,770, 1044, 1209,1357, 1431, 1489, 1547,1589,
1
3060; H NMR (300 MHz, CDCl3) d 3.91 (s, 3H), 7.00 (dd,
J¼2.4, 8.1 Hz, 1H), 7.38e7.84 (m, 7H), 7.68e7.74 (m, 3H),
7.80 (s, 1H), 7.89 (d, J¼8.1 Hz, 1H), 8.24 (d, J¼8.1 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 55.36, 112.63, 115.41, 119.37,
119.98, 125.58, 125.80, 126.31, 128.36, 128.54, 129.45, 129.52,
129.75, 130.10, 138.34, 141.09, 148.71, 149.07, 156.60, 160.10;
EIMS (m/z, relative intensity): 311 (Mþ, 75), 310 (100), 281(35),
267(7),241(3),204(9), 176(3),156(7),140(6), 133(8),121(5),
105(2);HRMScalcdfor C22H17ON: 311.1310;found:311.1312.
4.4.9. 2-(3-Bromophenyl)-4-phenylquinoline (5g)
IR (film): 701, 773, 793, 878, 1073, 1545, 1588, 3062; H
1
NMR (300 MHz, CDCl3) d 7.36 (t, J¼7.8 Hz, 1H), 7.44e7.58
(m, 7H), 7.70e7.73 (s, 1H), 7.75 (s, 1H), 7.90 (dd, J¼0.75,
8.11 Hz, 1H), 8.09 (dt, J¼0.72, 7.8 Hz, 1H), 8.21e8.24 (m,
1H), 8.38 (t, J¼1.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) d
118.95, 123.09, 125.63, 125.87, 126.01, 126.65, 128.48, 128.60,
129.49, 129.69, 130.11, 130.27, 130.56, 132.18, 138.11, 141.57,
148.67, 149.42, 155.06; EIMS (m/z, relative intensity): 360
[(Mþ1)þ, 100], 359 (Mþ, 93), 278 (36), 252 (6), 176 (13),
151 (7), 139 (26); HRMS calcd for C21H14N79Br: 359.0310;
found: 359.0300.
4.4.14. 2-(4-Bromophenyl)-4-phenylquinoline (5j)
IR (film): 702, 772, 829, 1009, 1071, 1357, 1417, 1487, 1543,
1589; 1H NMR (300 MHz, CDCl3) d 7.44e7.76 (m, 10H), 7.89
(d, J¼8.1 Hz, 1H), 8.07 (d, J¼8.7 Hz, 2H), 8.21 (d, J¼8.4 Hz,
1H); 13C NMR (75 MHz, CDCl3) d 118.80, 123.91, 125.65,
125.78, 126.53, 128.47, 128.60, 129.05, 129.49, 129.67, 130.04,
131.91, 138.17, 138.41, 148.71, 149.37, 155.49; EIMS (m/z, rel-
ative intensity): 361 (91), 359 (Mþ, 100), 278 (27), 261 (23), 202
(14), 181 (5), 169 (37), 139 (20); HRMS calcd for C21H14N79Br
359.0310; found: 359.0302.
4.4.10. N-[1-(3-Bromophenyl)-3-phenylprop-2-ynyl]-4-
methylbenzenamine (4h)
1
IR (film): 690, 756, 788, 807, 1518, 1616, 3020; H NMR
(300 MHz, CDCl3) d 2.24 (s, 3H), 4.03 (d, J¼6.4 Hz, 1H), 5.41
(d, J¼6.4 Hz, 1H), 7.01 (dd, J¼0.6, 8.4 Hz, 1H), 7.21e7.30
(m, 4H), 7.38e7.46 (m, 3H), 7.54e7.58 (m, 1H), 7.80 (t,
J¼1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 20.44, 50.45,
85.40, 87.85, 114.30, 122.45, 122.74, 125.83, 128.11, 128.22,
129.68, 130.24, 130.28, 131.06, 131.73, 142.25, 143.88; EIMS
(m/z, relative intensity): 375 (Mþ, 16), 368 (3), 269 (100), 220
(22), 189 (38), 163 (3), 139 (2); HRMS calcd for C22H18N79Br:
375.0623; found: 375.0621.
4.4.15. 2-(4-Phenyphenyl)-4-phenylquinoline (5l)
IR (film): 699, 721, 731, 769, 847, 1007, 1358, 1415, 1445,
1
1487, 1542, 1589; H NMR (300 MHz, CDCl3) d 7.34e7.55
(m, 9H), 7.66e7.75 (m, 5H), 7.76e7.91 (m, 2H), 8.24e8.29
(m, 3H); 13C NMR (75 MHz, CDCl3) d 119.18, 125.62,
125.76, 126.30, 127.11, 127.50, 127.54, 127.93, 128.38, 128.57,
128.80, 129.53, 129.54, 130.09, 138.36, 138.45, 140.53, 142.02,
148.82, 149.11, 156.35; EIMS (m/z, relative intensity): 357
(Mþ, 100), 280 (3), 202 (14), 178 (10), 170 (2); HRMS calcd
for C27H19N: 357.1518; found: 357.1521.
4.4.11. 2-(3-Bromophenyl)-6-methyl-4-phenylquinoline (5h)
IR (film): 700, 765, 790, 825, 1491, 1546, 1587, 1714, 3058;
1H NMR (300 MHz, CDCl3) d 2.45 (s, 3H), 7.34 (t, J¼7.8 Hz,
1H), 7.49e7.56 (m, 7H), 7.63 (s, 1H), 7.70 (s, 1H), 8.07 (d,
J¼8.4 Hz, 1H), 8.11 (d, J¼8.4 Hz, 1H), 8.36 (s, 1H); 13C
NMR (75 MHz, CDCl3) d 21.80, 118.98, 123.06, 124.35,
125.82, 125.88, 128.35, 128.57, 129.46, 129.83, 130.21, 130.44,
131.92, 131.97, 136.64, 138.34, 141.68, 147.26, 148.65, 154.15;
EIMS (m/z, relative intensity): 373 (Mþ, 100), 358 (38), 294
(23), 278 (16), 265 (2), 252 (2), 261 (10), 202 (5), 187 (3), 139
(24), 125 (6); HRMS calcd for C22H16N79Br: 373.0466; found:
373.0467.
4.4.16. N-[3-(Naphthalen-1-yl)-1-phenylprop-2-ynyl]
benzenamine (4m)
1
IR (film): 696, 749, 774, 799, 1501, 1601, 3054, 3401; H
NMR (200 MHz, CDCl3) d 4.30 (br, 1H), 5.54 (s, 1H), 5.67e
6.89 (m, 3H), 7.19e7.50 (m, 8H), 7.61e7.92 (m, 5H), 8.06e
8.12 (m, 1H); 13C NMR (50 MHz, CDCl3) d 51.20, 83.40,
93.34, 114.66, 118.99, 120.42, 125.07, 126.18, 126.31, 126.75,
127.47, 128.16, 128.20, 128.76, 128.84, 129.22, 130.49, 133.10,
133.39, 139.56, 146.50; EIMS (m/z, relative intensity): 333
(Mþ, 7), 241 (100), 149 (3), 77 (2); HRMS calcd for
C25H19N: 333.1518; found: 333.1513.
4.4.12. N-[1-(3-Methoxyphenyl)-3-phenylprop-2-ynyl]
benzenamine (4i)
4.4.17. 4-(Naphthalen-1-yl)-2-phenylquinoline (5m)
IR (film): 690, 754, 787, 871, 1046, 1154, 1255, 1433, 1489,
1501, 1600, 2924; 1H NMR (300 MHz, CDCl3) d 3.80 (s, 3H),
4.14 (br, 1H), 5.46 (s, 1H), 6.75e7.42 (m, 14H); 13C NMR
(75 MHz, CDCl3) d 50.60, 55.24, 84.96, 88.34, 112.86,
113.53, 114.04, 118.56, 119.53, 122.71, 128.18, 128.27,
129.13, 129.77, 131.71, 141.29, 146.48, 159.90; EIMS (m/z,
relative intensity): 313 (Mþ, 9), 221 (100), 211 (45), 178 (14),
167 (6); HRMS calcd for C22H19ON: 313.1467; found:
313.1469.
IR (film): 694, 731, 770, 804, 908, 1396, 1547, 1590, 3381;
1H NMR (300 MHz, CDCl3) d 7.29e7.73 (m, 11H), 7.91e
8.00 (m, 3H), 8.19e8.22 (m, 2H), 8.30 (d, J¼8.4 Hz, 1H); 13
C
NMR (75 MHz, CDCl3) d 120.47, 125.27, 125.96, 126.12,
126.16, 126.34, 126.48, 127.00, 127.38, 127.62, 128.30, 128.76,
128.84, 129.43, 129.71, 129.87, 131.92, 133.47, 135.89, 139.36,
148.11, 148.35, 156.78; EIMS (m/z, relative intensity): 331
(Mþ, 100), 252 (16), 226 (10), 164 (14); HRMS calcd for
C25H17N: 331.1361; found: 331.1367.

F. Xiao et al. / Tetrahedron 64 (2008) 2755e2761
2761
~
~
´
Munoz, M. P.; Bunuel, E.; Nevado, C.; Cardenas, D. J.; Echavarren, A. M.
Angew. Chem., Int. Ed. 2004, 43, 2402; (c) Kennedy-Smith, J. J.; Staben,
S. T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526; (d) Mamane, V.;
4.4.18. N-(1-Phenyl-5-(tetrahydro-2H-pyran-2-yloxy)-
pent-2-ynyl)benzenamine (4o)
IR (film): 697, 750, 1032, 1502, 1601, 2941; 1H NMR
(300 MHz, CDCl3) d 1.23e1.78 (m, 6H), 2.50 (dt, J¼2.1,
7.2 Hz, 2H), 3.41e3.54 (m, 2H), 3.74e3.83 (m, 2H), 4.04 (s,
1H), 4.58 (dd, J¼3, 6.6 Hz, 1H), 5.22 (s, 1H), 6.67 (m, 3H),
7.13e7.38 (m, 5H), 7.54e7.58 (m, 2H); 13C NMR (75 MHz,
CDCl3) d 19.23, 20.28, 25.36, 30.45, 50.05, 61.96, 61.98,
65.60, 65.65, 80.21, 82.31, 98.58, 98.64, 113.82, 118.28,
127.15, 127.48, 127.83, 128.58, 128.73, 129.04, 140.13,
146.61; EIMS (m/z, relative intensity): 335 (Mþ, 30), 263 (4),
250 (26), 232 (15), 219 (10), 206 (10), 187 (12), 171 (30), 141
(74); HRMS calcd for C22H25O2N: 335.1885; found: 335.1881.
Gress, T.; Krause, H.; Furstner, A. J. Am. Chem. Soc. 2004, 126, 8654;
¨
(e) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem.,
Int. Ed. 2004, 43, 5350; (f) Luzung, M. R.; Markham, J. P.; Toste,
F. D. J. Am. Chem. Soc. 2004, 126, 10858; (g) Zhang, L.; Kozmin,
S. A. J. Am. Chem. Soc. 2004, 126, 11806; (h) Sherry, B. D.; Toste,
F. D. J. Am. Chem. Soc. 2004, 126, 15978; (i) Nieto-Oberhuber, C.; Lopez,
S.; Echavarren, A. M. J. Am. Chem. Soc. 2005, 127, 6178; (j) Zhang, L.;
Kozmin, S. A. J. Am. Chem. Soc. 2005, 127, 6962; (k) Gagosz, F. Org.
Lett. 2005, 7, 4129.
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5. Genin, E.; Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J.-P.;
Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112.
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Int. Ed. 2000, 39, 2285; (b) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650; (c) Asao, N.; Aikawa,
H.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 7458; (d) Yao, T.; Zhang,
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Acknowledgements
The project is generously supported by Natural Science
Foundation of China (Grant Nos. 20572002, 20521202,
20772003) and the Ministry of Education of China (Cheung
Kong Scholars Program).
7. Morita, N.; Krause, N. Angew. Chem., Int. Ed. 2006, 45, 1897.
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