Palladium-catalyzed intermolecular domino reaction of gem-dibromoenynes with anilines; A one-pot synthesis of quinolines and quinolinones

Article abstract of DOI:10.1055/s-0032-1316613

An efficient domino process involving palladium-catalyzed amination of an alkenyl bromide, 1,5-H transfer, annulation via 6-exo-dig electrophilic cyclization, and palladium-catalyzed etherification, is described. This reaction provides an efficient one-pot synthesis of multi-substituted quinolines and quinolinones from gem-dibromoenynes and anilines. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1316613

2754▌
PAPER
paper
Palladium-Catalyzed Intermolecular Domino Reaction of gem-Dibromo-
enynes with Anilines; A One-Pot Synthesis of Quinolines and Quinolinones
One-Pot Synthesis of Quinolines and Quinolinones
Tianhao Meng,a Wen-Xiong Zhang,b Hui-Jun Zhang,b Yun Liang,b Zhenfeng Xi*b
a
Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190,
P. R. of China
b
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of
Ministry of Education, College of Chemistry, Peking University, Beijing 100871, P. R. of China
Fax +86(10)62759728; E-mail: zfxi@pku.edu.cn
Received: 14.05.2012; Accepted after revision: 11.06.2012
gem-dihaloolefins is rare.6f,8 This palladium-catalyzed in-
Abstract: An efficient domino process involving palladium-cata-
termolecular domino reaction between amines and gem-
lyzed amination of an alkenyl bromide, 1,5-H transfer, annulation
dibromoenynes thus provides an efficient alternative syn-
thesis of quinolines and quinolinones.
via 6-exo-dig electrophilic cyclization, and palladium-catalyzed
etherification, is described. This reaction provides an efficient one-
pot synthesis of multi-substituted quinolines and quinolinones from
gem-dibromoenynes and anilines.
First, we investigated the model reaction between aniline
and compound 1a (Table 1). The reaction was initially
carried out in toluene at 110 °C for two hours with
NaOt-Bu as the base. Various palladium catalysts (Table
1, entries 1–4) and a series of ligands (Table 1, entries 5–
15) were examined. Although the Buchwald biaryl phos-
phine ligands showed better activity than Ph3P and Cy3P,
the bidentate ligand DPEPhos [bis(2-diphenylphosphino-
phenyl)ether] proved to be more efficient in this reaction.
It was also noticed that the reactivity diminished when the
solvent was changed from toluene to 1,4-dioxane or
DME. Notably, the choice of base seems crucial for this
transformation; NaOt-Bu was found to be the most effec-
tive base, whereas other bases such as LiOt-Bu or KOt-Bu
did not afford any expected products. After extensive
screening, optimal reaction conditions were established
{[Pd2(dba)3] (2.5 mol%), DPEPhos (10 mol%), NaOt-Bu
(5 equiv), toluene, 110 °C, 2 h} with which polysubstitut-
ed quinoline 3a was obtained in 68% isolated yield (Table
1, entry 12).
Key words: alkenes, enynes, etherification, quinoline, quinolinone
The gem-dihaloolefins have become important and versa-
tile building blocks in palladium-catalyzed domino reac-
tions leading to heterocyclic compounds.1 Recently,
several elegant methods have been discovered that can be
used to convert gem-dihaloolefins into indoles,2 benzo-
thiophenes,2a,3 benzofurans,2a,4 isocoumarins,5 and other
heterocycles via intramolecular cyclization.1,6 For exam-
ple, Lautens et al. reported the intramolecular amination
of amino-containing gem-dibromoolefins to provide the
brominated indoles, in which the remaining C–Br bond
could further undergo Suzuki coupling.2b Xu et al. report-
ed a palladium-catalyzed intermolecular amidation reac-
tion of gem-dihaloolefins with aryl amines yielding
acyclic carboxamides upon hydrolysis.7
Our group has been interested in the preparation and syn-
thetic applications of polyhalo conjugated com-
pounds.8a,9,10 Herein, we report an intermolecular
amination between amines and gem-dibromoenynes that
efficiently yields quinolines and quinolinones. Mechanis-
tic investigations have revealed that a domino process in-
volving palladium-catalyzed amination of the alkenyl
bromide, 1,5-H transfer, annulation via 6-exo-dig electro-
philic cyclization, and palladium-catalyzed etherification
took place, resulting in the formation of Csp2–Csp, Csp2–N,
and Csp2–O bonds. The quinoline unit is an important skel-
eton found in a variety of bioactive compounds.11 Most of
the known synthetic methods for accessing functionalized
quinolines are based on the reaction of substituted anilines
with carbonyl compounds.12–14 Synthesis of N-heterocy-
cles via intermolecular amination between amines and
Because the substituents on the quinoline has such a great
influence on its properties, the scope of this domino reac-
tion was studied by testing various substituted anilines
2b–k, with the aim of synthesizing a diverse range of
quinolines. As shown in Table 2, various quinolines 3d–
m could be obtained in moderate to high isolated yields
under the above optimized reaction conditions. Anilines
substituted with either electron-withdrawing or electron-
donating groups could both be applied in this reaction.
Naphthylamine (2h) and the heteroaromatic amine (2i)
could also be used to provide the corresponding quinoline
derivatives.
It is noteworthy that, along with the formation of quino-
lines 3, a small amount of the corresponding quinolinones
4 were formed, which could be separated from quinolines
3. It became clear that quinolinone 4 was formed through
hydrolysis of quinoline 3. Quantitative transformation of
quinoline 3 into quinolinone 4 was observed when pure
SYNTHESIS 2012, 44, 2754–2762
Advanced online publication: 23.07.2012
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0
3
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7
8
8
1
1
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DOI: 10.1055/s-0032-1316613; Art ID: SS-2012-H0443-OP
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Synthesis of Quinolines and Quinolinones
2755
electrophilic cyclization,19 and palladium-catalyzed ether-
ification.20,21 The second pathway might involve: palladi-
um-catalyzed etherification, amination, 1,5-H shift, and
6-exo-dig electrophilic cyclization.
Table 1 Reaction Optimizationa
Bu
Bu
cat. [Pd] (5 mol%)
Bu
Br
Bu
ligand (10 mol%)
+
To gain a better understanding of the present reaction
mechanism, three different experiments were carried out.
First, the two-component coupling between the conjugat-
ed cis-bromo alkenyne 5 and aniline 2a was carried out
under the above reaction conditions, providing quinoline
6 in 57% isolated yield as well as pyrrole 7 in 16% isolat-
ed yield (Scheme 2).22,23 The formation of 6 presumably
arises from 6-exo-dig electrophilic cyclization of the al-
kynylenamine intermediate 8, whereas pyrrole derivative
7 should be generated via 5-endo-dig hydroamination of
8. This result clearly shows the prior palladium-catalyzed
amination with one bromine is reasonable and should re-
sult in the formation of quinoline 6, which strongly sup-
ports Step 1 of the proposed pathway I shown in Scheme
1.
NaOt-Bu (5 equiv)
Br
NH
2 solvent, 110 °C, 2 h
N
Ot-Bu
1a
2a
3a
Entry [Pd]
Ligand
Base
Solvent
Yield
(%)a
1
2
PdCl2
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
trace
trace
trace
9
Pd(OAc)2
Pd2(dba)3
Pd(PPh3)4
3
4
5
Pd(OAc)2 XPhos
53
6
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
XPhos
SPhos
65 (61)
57
7
A deuterium-labeling experiment using aniline-D2 and 1a
was carried out in the presence of anhydrous NaOt-Bu
(Scheme 3). The gem-dihaloenyne 1a was converted com-
pletely in refluxing toluene within two hours, resulting in
the formation of the product 3a-D/H in 65% isolated
yield. The deuterium on the C5 position of quinoline 3a-
D/H originates from aniline-D2, which strongly supports
the proposed 1,5-H shift shown in Scheme 1.
8
RuPhos
47
9
DavePhos NaOt-Bu toluene
57
10
11
12
13
14
15
16
17
18
19
PPh3
NaOt-Bu toluene
NaOt-Bu toluene
NaOt-Bu toluene
33
PCy3
trace
72 (68)
31
DPEPhos
Finally, an experiment was designed to investigate at
which step the etherification reaction occurs; either the
first step in pathway II or in the last step in pathway I. No
reaction took place when 2-bromoquinoline 9 was treated
with three equivalents of NaOt-Bu without the palladium
catalyst. Under the optimized reaction conditions used
above, as shown in Scheme 4, the ether-containing quino-
line 10 was obtained in 70% isolated yield, along with for-
mation of the corresponding quinolinone 11 in 21%
isolated yield. This result and other experimental observa-
tions show that pathway I (Scheme 1) is more likely.
XantPhos NaOt-Bu toluene
DPPF
NaOt-Bu toluene
NaOt-Bu toluene
LiOt-Bu toluene
51
DPPP
52
DPEPhos
DPEPhos
DPEPhos
DPEPhos
trace
trace
KOt-Bu
toluene
NaOt-Bu 1,4-dioxane 66b
NaOt-Bu DME
24b
a GC yields. Isolated yields given in parentheses.
b Heated to reflux.
In summary, we have developed a domino palladium-
catalyzed amination, C–C bond formation, and C–O cou-
pling process. This method provides an efficient synthesis
of multi-substituted quinolines and quinolinones from
gem-dibromoenynes and anilines.
quinoline 3 was treated with aqueous 3 M HCl. Accord-
ingly, as shown in Table 2, quinolinones 4d–m were iso-
lated in moderate to high yields as the sole products when
the one-pot reaction mixture was quenched with aqueous
3 M HCl.
Unless otherwise noted, all starting materials were commercially
available and were used without further purification. All reactions
were carried out either using standard Schlenk techniques or under
a nitrogen atmosphere in a glovebox. The nitrogen in the glovebox
was constantly circulated through a copper/molecular sieve catalyst
unit. The oxygen and moisture concentrations in the glovebox at-
mosphere were monitored by an O2/H2 Combi-Analyzer to ensure
both were always below 1 ppm. Solvents were purified by a Solvent
Purification System and dried over fresh Na chips in the glovebox.
We also investigated other gem-dibromoenynes with dif-
ferent substituents on the unsaturated skeleton. As sum-
marized in Table 2 (entries 2 and 3), derivatives 3 and 4
were obtained in moderate isolated yields from propyl-
substituted enyne (1b) and hexyl-substituted enyne (1c),
respectively, with aniline 2a.
1H and 13C NMR spectra were recorded with a JEOL JNM-AL 300
Two plausible catalytic pathways for the formation of
quinolines 3 from gem-dihaloenyne 1 are presented in
Scheme 1. The first pathway (I) might involve four subse-
quent steps: palladium-catalyzed amination of the alkenyl
bromides,15–17 1,5-H transfer,18 annulation via 6-exo-dig
1
spectrometer (FT, 300 MHz for H; 75 MHz for 13C), a Bruker
DMX 300 spectrometer (FT, 300 MHz for 1H; 75 MHz for 13C), a
Bruker ARX 400 spectrometer (FT, 400 MHz for 1H; 100 MHz for
1
13C), a Bruker AVANCE 400 spectrometer (FT, 400 MHz for H;
100 MHz for 13C) or a Bruker AVANCE III 500 spectrometer (FT,
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2754–2762

2756
T. Meng et al.
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Table 2 Domino Three-Component Synthesis of Quinolines 3 and Quinolinones 4
R1
R1
R1
Pd2(dba)3 (2.5 mol%)
R1
R1
O
R1
Br
DPEPhos (10 mol%)
R2
R2
R2
+
+
NaOt-Bu (5 equiv)
toluene, 110 °C, 2 h
NH2
N
Ot-Bu
N
Br
H
1
2
3
4
3 M HCl
100%
Entry
Amines 2
Quinolines 3 (Yield) [%]a
Quinolinones 4 (Yield) [%]b
R1
R1
R2
R2
R1
O
R2
R1
NH2
N
N
Ot-Bu
H
1
2
3
4
5
6
2a: R2 = H
2b: R2 = F
3a: R1 = Bu (68%)
3b: R1 = Pr (52%)
3c: R1 = Hex (63%)
3d: R1 = Bu (50%)
3e: R1 = Bu (59%)
3f: R1 = Bu (47%)
R1
4a: R1 = Bu (74%)
4b: R1 = Pr (61%)
4c: R1 = Hex (70%)
4d: R1 = Bu (64%)
4e: R1 = Bu (65%)
4f: R1 = Bu (63%)
R1
2c: R2 = OMe
2d: R2 = Bn
R2
R1
R1
NH2
N
O
N
Ot-Bu
H
R2
R2
7
8
9
2e: R2 = i-Pr
2f: R2 = OMe
2g: R2 = Ph
3g: R1 = Bu (66%)
3h: R1 = Bu (72%)
4g: R1 = Bu (73%)
4h: R1 = Bu (81%)
3i: R1 = Bu (62%)
4i: R1 = Bu (70%)
Bu
Bu
X
Bu
Bu
N
H
O
N
Ot-Bu
NH2
X
X
10
11
2h: X = C
2i: X = N
3j (60%)
3k (32%)
4j (71%)
4k (43%)
Bu
Bu
OMe
OMe
OMe
Bu
Bu
O
MeO
NH2
N
Ot-Bu
N
H
OMe
OMe
12
13
2j
3l (50%)
4l (63%)
Bu
Bu
OMe
OMe
OMe
Bu
O
Bu
MeO
NH2
MeO
N
H
MeO
N
Ot-Bu
2k
3m (45%)
4m (63%)
a Isolated yields of quinolines 3.
b Aq 3 M HCl was added to the crude mixture and stirred for 30 min; isolated yields of quinolinones 4 are given in parentheses.
Synthesis 2012, 44, 2754–2762 © Georg Thieme Verlag Stuttgart · New York

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One-Pot Synthesis of Quinolines and Quinolinones
2757
R1
R2
Br
R3
II
I
Pd-catalyzed
amination
NH2
Pd-catalyzed
etherification
Br
NaOt-Bu
R1
R1
R1
R2
Br
R2
R2
R3
N
H
Br
Ot-Bu
Br
N
H
R3
Pd-catalyzed
amination
1,5-H shift
H
1,5-H shift
H
R1
R1
R2
R1
R2
R2
Br
H
R3
Br
N
R3
Ot-Bu
N
N
R3
H
H
N
R1
6-exo-dig
H
electrophilic
cyclization
1,5-H shift
R2
R3
H
H
H
R1
Ot-Bu
NaOt-Bu
R1
R2
Pd-catalyzed
etherification
R2
Br
6-exo-dig
electrophilic
cyclization
H
R3
Ot-Bu
N
N
R3
Scheme 1 Proposed reaction mechanism
Pd2(dba)3 (2.5 mol%)
DPEphos (10 mol%)
Ph
Ph
N
+
2a
+
NaOt-Bu (3 equiv)
toluene, 110 °C, 2 h
Br
Ph
Ph
7 (16%)
N
Ph
Ph
5
6 (57%)
6-exo-dig
electrophilic
cyclization
5-endo-dig
hydroamination
Ph
N
H
Ph
8
Scheme 2 Palladium-catalyzed amination of monohaloenyne 5 affording quinoline 6 and pyrrole 7
D/H (D: 86%)
H
Bu
Bu
5
Pd2(dba)3 (2.5 mol%)
DPEPhos (10 mol%)
3
Bu
Br
Bu
+
NaOt-Bu (5 equiv)
toluene, 110 °C, 2 h
Br
ND2
aniline-D2
N 1
Ot-Bu
1a
3a-D/H (65%)
Scheme 3 Deuterium-labeling experiment confirming the 1,5-H-shift
Pd2(dba)3 (2.5 mol%)
DPEphos (10 mol%)
+
NaOt-Bu (3.0 equiv)
toluene, 110 °C, 2 h
N
Br
N
H
O
N
Ot-Bu
9
10 (70%)
11 (21%)
Scheme 4 Control experiment used to investigate the etherification reaction
© Georg Thieme Verlag Stuttgart · New York
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T. Meng et al.
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1
500 MHz for H; 125 MHz for 13C) at r.t. in CDCl3 solutions and
with tetramethylsilane (δ = 0.00 ppm) as internal standard, unless
otherwise noted. Infrared spectra (IR) were recorded with a Thermo
Nicolet Avatar 330 FT-IR spectrophotometer. High-resolution
mass spectra (HRMS) were recorded with a Bruker Apex IV FTMS
mass spectrometer using electrospray ionization (ESI) and FT-ICR
mass analyser or a Waters Micromass GCT mass spectrometer us-
ing electron-ionization (EI) and a TOF mass analyzer. The gem-di-
haloenynes 1 were prepared from 1,1,4,4-tetrahalo-1,3-butadienes
through the Fritsch–Buttenberg–Wiechell (FBW) rearrangement
mediated by an organolithium compound.10b
2-tert-Butoxy-3-butyl-6-fluoro-4-pentylquinoline (3d)
Yield: 50% (35 mg); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.91–1.00 (m, 6 H, CH3), 1.37–
1.53 (m, 10 H, CH2), 1.68 (s, 9 H, CH3), 2.68 (t, J = 7.8 Hz, 2 H,
CH2), 2.89 (t, J = 8.1 Hz, 2 H, CH2), 7.21–7.28 (m, 1 H, CH), 7.40–
7.45 (m, 1 H, CH), 7.68–7.73 (m, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 13.98, 14.03, 22.5, 23.1, 26.8, 28.4,
28.6 (3CH3), 30.0, 31.8, 32.4, 79.6, 107.4 (d, JC–F = 22.3 Hz), 116.8
(d, JC–F = 24.7 Hz), 124.7 (d, JC–F = 8.6 Hz), 126.5, 129.7 (d, JC–F
8.7 Hz), 141.8, 145.2 (d, JC–F = 4.3 Hz), 159.0 (d, JC–F = 239.3 Hz),
160.0.
=
HRMS (ESI): m/z [M + H]+ calcd for C22H33FNO+: 346.2541;
found: 346.2538.
Preparation of Quinolines 3 and Quinolinones 4; General Pro-
cedure
[Pd2(dba)3] (4.6 mg, 0.005 mmol), DPEPhos (10.2 mg, 0.02 mmol)
and toluene (2.0 mL) were placed in an oven-dried 25 mL flask, and
the mixture was stirred at r.t. for 15 min, then gem-dihaloenyne 1
(0.2 mmol), aniline 2 (0.24 mmol), and NaOt-Bu (96 mg, 1.0 mmol)
were added. The flask was then placed in a preheated oil bath
(110 °C) and stirred for 2 h. After cooling to r.t., the solvent was
evaporated under vacuum and the residue was purified by chroma-
tography (EtOAc–pentane, 0→10%) to give the quinoline product
3. To obtain the corresponding quinolinone product 4, excess 3 M
HCl was added and the solution was stirred for 1 h. The reaction
mixture was neutralized with NaHCO3 and extracted with EtOAc
(3 × 3 mL). The solvent was then evaporated in vacuo and the crude
product was purified by column chromatography over silica gel
(EtOAc–pentane, 50→100%).
2-tert-Butoxy-3-butyl-6-methoxy-4-pentylquinoline (3e)
Yield: 59% (42 mg); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 0.92–0.99 (m, 6 H, CH3), 1.38–
1.53 (m, 8 H, CH2), 1.59–1.65 (m, 2 H, CH2), 1.67 (s, 9 H, CH3),
2.68 (t, J = 7.7 Hz, 2 H, CH2), 2.92 (t, J = 8.2 Hz, 2 H, CH2), 3.90
(s, 3 H, CH3), 7.16–7.19 (m, 2 H, CH), 7.67 (d, J = 9.4 Hz, 1 H,
CH).
13C NMR (100 MHz, CDCl3): δ = 14.00, 14.05, 22.5, 23.1, 26.8,
28.3, 28.7 (3CH3), 29.8, 31.9, 32.4, 55.5, 79.1, 103.7, 118.1, 124.7,
125.8, 129.2, 140.4, 144.8, 155.5, 159.2.
+
HRMS (ESI): m/z [M + H]+ calcd for C23H36NO2 : 358.2741; found:
358.2737.
2-tert-Butoxy-3-butyl-4-pentylquinoline (3a)
6-Benzyl-2-tert-butoxy-3-butyl-4-pentylquinoline (3f)
Yield: 68% (45 mg); yellow oil.
Yield: 47% (39 mg); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.90–0.99 (m, 6 H, CH3), 1.38–
1.53 (m, 10 H, CH2), 1.69 (s, 9 H, CH3), 2.69 (t, J = 8.3 Hz, 2 H,
CH2), 2.96 (t, J = 7.8 Hz, 2 H, CH2), 7.31 (t, J = 7.5 Hz, 1 H, CH),
7.49 (t, J = 7.2 Hz, 1 H, CH), 7.73–7.83 (m, 2 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 26.7, 28.2,
28.7 (3CH3), 30.3, 31.9, 32.4, 79.5, 123.1, 123.4, 124.2, 125.5,
127.5, 127.9, 145.0, 145.8, 160.4.
1H NMR (300 MHz, CDCl3): δ = 0.89–0.98 (m, 6 H, CH3), 1.34–
1.55 (m, 10 H, CH2), 1.67 (s, 9 H, CH3), 2.67 (t, J = 7.7 Hz, 2 H,
CH2), 2.89 (t, J = 8.0 Hz, 2 H, CH2), 4.12 (s, 2 H, CH2), 7.19–7.34
(m, 6 H, CH), 7.56 (s, 1 H, CH), 7.66 (d, J = 8.4 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.01, 14.04, 22.5, 23.1, 26.7, 28.1,
28.7 (3CH3), 30.2, 31.9, 32.3, 42.1, 79.3, 123.1, 124.1, 125.6, 126.0,
128.0, 128.4 (2CH), 128.9 (2CH), 129.0, 135.7, 141.4, 143.7, 145.5,
160.2.
HRMS (ESI): m/z [M + H]+ calcd for C22H34NO+: 328.2635; found:
328.2629.
HRMS (ESI): m/z [M + H]+ calcd for C29H40NO+: 418.3104; found:
418.3107.
2-tert-Butoxy-4-butyl-3-propylquinoline (3b)
Yield: 52% (31 mg); yellow oil.
2-tert-Butoxy-3-butyl-8-isopropyl-4-pentylquinoline (3g)
Yield: 66% (49 mg); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.98–1.03 (m, 6 H, CH3), 1.49–
1.60 (m, 6 H, CH2), 1.69 (s, 9 H, CH3), 2.67 (t, J = 7.7 Hz, 2 H,
CH2), 2.97 (t, J = 7.5 Hz, 2 H, CH2), 7.32 (t, J = 7.5 Hz, 1 H, CH),
7.49 (t, J = 7.5 Hz, 1 H, CH), 7.75 (d, J = 8.4 Hz, 1 H, CH), 7.83 (d,
J = 8.4 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.6, 23.1, 23.3, 27.9, 28.7
(3CH3), 29.1, 32.7, 79.4, 123.1, 123.5, 124.2, 125.4, 127.5, 127.9,
145.1, 145.9, 160.4.
1H NMR (300 MHz, CDCl3): δ = 0.92–1.00 (m, 6 H, CH3), 1.34–
1.53 (m, 16 H, CH2, CH3), 1.71 (s, 9 H, CH3), 2.70 (t, J = 6.2 Hz,
2 H, CH2), 2.96 (t, J = 6.8 Hz, 2 H, CH2), 4.15–4.23 (m, 1 H, CH),
7.31 (t, J = 7.8 Hz, 1 H, CH), 7.45 (d, J = 6.3 Hz, 1 H, CH), 7.70 (d,
J = 8.4 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 23.6 (2CH3),
26.8, 27.3, 28.4, 28.6 (3CH3), 30.3, 31.9, 32.5, 78.8, 121.2, 123.0,
123.3, 124.1, 125.1, 142.7, 145.6, 146.3, 159.3.
HRMS (ESI): m/z [M + H]+ calcd for C20H30NO+: 300.2322; found:
300.2316.
HRMS (ESI): m/z [M + H]+ calcd for C25H40NO+: 370.3104; found:
370.3103.
2-tert-Butoxy-4-heptyl-3-hexylquinoline (3c)
Yield: 63% (48 mg); yellow oil.
2-tert-Butoxy-3-butyl-8-methoxy-4-pentylquinoline (3h)
Yield: 72% (51 mg); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.88–0.92 (m, 6 H, CH3), 1.31–
1.63 (m, 18 H, CH2), 1.69 (s, 9 H, CH3), 2.68 (t, J = 7.8 Hz, 2 H,
CH2), 2.95 (t, J = 8.1 Hz, 2 H, CH2), 7.31 (t, J = 7.5 Hz, 1 H, CH),
7.49 (t, J = 7.5 Hz, 1 H, CH), 7.75 (d, J = 8.2 Hz, 1 H, CH), 7.82 (d,
J = 8.2 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.1 (2CH3), 22.7 (2CH2), 27.1,
28.2, 28.7 (3CH3), 29.1, 29.7, 29.8, 30.2, 30.6, 31.7, 31.8, 79.5,
123.1, 123.5, 124.2, 125.6, 127.5, 127.9, 145.0, 145.8, 160.4.
1H NMR (500 MHz, CDCl3): δ = 0.91–0.98 (m, 6 H, CH3), 1.37–
1.53 (m, 8 H, CH2), 1.58–1.64 (m, 2 H, CH2), 1.71 (s, 9 H, CH3),
2.69 (t, J = 7.8 Hz, 2 H, CH2), 2.94 (t, J = 8.3 Hz, 2 H, CH2), 3.99
(s, 3 H, CH3), 6.93 (d, J = 7.2 Hz, 1 H, CH), 7.22 (t, J = 8.1 Hz, 1 H,
CH), 7.42 (d, J = 7.7 Hz, 1 H, CH).
13C NMR (125 MHz, CDCl3): δ = 14.00, 14.04, 22.5, 23.1, 26.8,
28.6, 28.7 (3CH3), 30.3, 31.9, 32.4, 56.7, 79.5, 108.1, 115.9, 122.9,
125.5, 125.7, 136.8, 146.0, 155.1, 159.6.
HRMS (ESI): m/z [M + H]+ calcd for C26H42NO+: 384.3261; found:
384.3258.
Synthesis 2012, 44, 2754–2762
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of Quinolines and Quinolinones
2759
+
HRMS (ESI): m/z [M + H]+ calcd for C23H36NO2 : 358.2741; found:
358.2746.
3-Butyl-4-pentylquinolin-2(1H)-one (4a)
Yield: 74% (40 mg); colorless solid; mp 147.5–149.2 °C.
IR (film): 1654 (C=O) cm–1.
2-tert-Butoxy-3-butyl-4-pentyl-8-phenylquinoline (3i)
Yield: 62% (50 mg); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.92–1.01 (m, 6 H, CH3), 1.37–
1.70 (m, 10 H, CH2), 2.76 (t, J = 7.4 Hz, 2 H, CH2), 2.88 (t,
J = 8.0 Hz, 2 H, CH2), 7.17–7.22 (m, 1 H, CH), 7.39–7.46 (m, 2 H,
CH), 7.67 (d, J = 8.2 Hz, 1 H, CH), 12.08 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 26.7, 28.8,
29.7, 31.6, 32.4, 116.3, 120.1, 122.1, 124.2, 128.9, 131.2, 137.3,
147.5, 164.0.
1H NMR (400 MHz, CDCl3): δ = 0.93–0.98 (m, 6 H, CH3), 1.41–
1.55 (m, 17 H, CH2, CH3), 1.62–1.70 (m, 2 H, CH2), 2.69 (t,
J = 7.7 Hz, 2 H, CH2), 3.00 (t, J = 8.2 Hz, 2 H, CH2), 7.32–7.43 (m,
4 H, CH), 7.50–7.55 (m, 3 H, CH), 7.86 (d, J = 9.7 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 26.8, 28.3
(3CH3), 28.5, 30.4, 31.9, 32.5, 79.1, 122.7, 123.1, 124.6, 125.4,
126.4, 127.3 (2CH), 128.5, 130.7 (2CH), 139.7, 141.2, 143.0, 146.0,
159.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H26NO+: 272.2009; found:
272.2014.
HRMS (ESI): m/z [M + H]+ calcd for C28H38NO+: 404.2948; found:
404.2949.
4-Butyl-3-propylquinolin-2(1H)-one (4b)
Yield: 61% (30 mg); colorless solid; mp 135.2–136.9 °C.
IR (film): 1650 (C=O) cm–1.
2-tert-Butoxy-3-butyl-4-pentylbenzo[h]quinoline (3j)
Yield: 60% (45 mg); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 0.99–1.08 (m, 6 H, CH3), 1.51–
1.66 (m, 6 H, CH2), 2.74 (t, J = 7.8 Hz, 2 H, CH2), 2.90 (t,
J = 7.9 Hz, 2 H, CH2), 7.21 (t, J = 7.4 Hz, 1 H, CH), 7.38–7.46 (m,
2 H, CH), 7.69 (d, J = 8.2 Hz, 1 H, CH), 11.94 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.6, 22.7, 23.3, 28.6, 29.0,
32.1, 116.3, 120.1, 122.2, 124.3, 129.0, 130.9, 137.2, 147.8, 164.0.
1H NMR (300 MHz, CDCl3): δ = 0.92–1.02 (m, 6 H, CH3), 1.40–
1.59 (m, 10 H, CH2), 1.80 (s, 9 H, CH3), 2.75 (t, J = 7.7 Hz, 2 H,
CH2), 3.02 (t, J = 8.1 Hz, 2 H, CH2), 7.57–7.66 (m, 3 H, CH), 7.83
(t, J = 8.9 Hz, 2 H, CH), 9.08 (d, J = 7.8 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 26.7, 28.4,
28.7 (3CH3), 30.6, 32.0, 32.4, 79.3, 120.7, 121.9, 123.7, 124.6,
125.0, 125.9, 126.8, 127.3, 131.6, 133.1, 142.4, 146.8, 160.0.
HRMS (ESI): m/z [M + H]+ calcd for C16H22NO+: 244.1696; found:
244.1701.
HRMS (ESI): m/z [M + H]+ calcd for C26H36NO+: 378.2791; found:
378.2794.
4-Heptyl-3-hexylquinolin-2(1H)-one (4c)
Yield: 70% (46 mg); colorless solid; mp 145.6–147.4 °C.
IR (film): 1654 (C=O) cm–1.
2-tert-Butoxy-3-butyl-4-pentyl-1,9-phenanthroline (3k)
Yield: 32% (24 mg); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 0.89–0.93 (m, 6 H, CH3), 1.32–
1.62 (m, 18 H, CH2), 2.74 (t, J = 7.7 Hz, 2 H, CH2), 2.88 (t,
J = 8.0 Hz, 2 H, CH2), 7.20 (t, J = 7.6 Hz, 1 H, CH), 7.32 (d,
J = 8.1 Hz, 1 H, CH), 7.42 (t, J = 7.6 Hz, 1 H, CH), 7.68 (d,
J = 8.2 Hz, 1 H, CH), 11.42 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): δ = 14.1, 14.2, 22.7 (2CH2), 27.0, 28.9,
29.1, 29.3, 29.7, 30.0, 30.2, 31.8 (2CH2), 116.1, 120.2, 122.1, 124.4,
128.9, 131.3, 137.1, 147.5, 163.7.
1H NMR (500 MHz, CDCl3): δ = 0.95 (t, J = 7.3 Hz, 3 H, CH3),
1.00 (t, J = 7.2 Hz, 3 H, CH3), 1.40–1.68 (m, 10 H, CH2), 1.80 (s,
9 H, CH3), 2.77 (t, J = 7.9 Hz, 2 H, CH2), 3.04 (t, J = 8.3 Hz, 2 H,
CH2), 7.74 (d, J = 9.0 Hz, 1 H, CH), 7.93 (d, J = 9.1 Hz, 1 H, CH),
8.72 (d, J = 5.7 Hz, 1 H, CH), 8.77 (d, J = 5.6 Hz, 1 H, CH), 9.24 (s,
1 H, CH).
13C NMR (125 MHz, CDCl3): δ = 14.01, 14.05, 22.5, 23.2, 26.8,
28.5, 28.7 (3CH3), 30.5, 31.8, 32.4, 79.9, 117.6, 121.7, 123.0, 123.5,
127.4, 128.1, 135.6, 140.9, 144.3, 147.0, 151.0, 160.6.
HRMS (ESI): m/z [M + H]+ calcd for C22H34NO+: 328.2635; found:
328.2633.
HRMS (ESI): m/z [M + H]+ calcd for C25H35N2O+: 379.2744; found:
379.2744.
3-Butyl-6-fluoro-4-pentylquinolin-2(1H)-one (4d)
Yield: 64% (37 mg); colorless solid; mp 133.3–135.3 °C.
2-tert-Butoxy-3-butyl-5,8-dimethoxy-4-pentylquinoline (3l)
Yield: 50% (39 mg); yellow oil.
IR (film): 1654 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.92–1.01 (m, 6 H, CH3), 1.37–
1.58 (m, 10 H, CH2), 2.74–2.85 (m, 4 H, CH2), 7.16–7.42 (m, 3 H,
CH), 12.67 (s, 1 H, NH).
1H NMR (300 MHz, CDCl3): δ = 0.91–0.99 (m, 6 H, CH3), 1.38–
1.50 (m, 10 H, CH2), 1.70 (s, 9 H, CH3), 2.69 (t, J = 7.2 Hz, 2 H,
CH2), 3.18 (t, J = 6.5, 2 H, CH2), 3.86 (s, 3 H, CH3), 3.94 (s, 3 H,
CH3), 6.59 (d, J = 8.7 Hz, 1 H, CH), 6.86 (d, J = 8.7 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.1, 26.8, 29.0,
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.2, 22.5, 23.1, 26.1, 28.6
(3CH3), 31.2, 31.3, 32.0, 32.8, 55.6, 57.6, 79.4, 102.6, 108.7, 117.3,
125.8, 138.6, 147.6, 149.3, 151.3, 159.6.
29.5, 31.5, 32.3, 109.4 (d, JC–F = 22.8 Hz), 117.1 (d, JC–F
24.2 Hz), 117.8 (d, JC–F = 8.1 Hz), 121.0 (d, JC–F = 8.0 Hz), 132.4,
133.8, 146.8 (d, JC–F = 3.7 Hz), 158.1 (d, JC–F = 238.1 Hz), 163.9.
HRMS (ESI): m/z [M + H]+ calcd for C18H25FNO+: 290.1915;
found: 290.1915.
=
+
HRMS (ESI): m/z [M + H]+ calcd for C24H38NO3 : 388.2846; found:
388.2836.
3-Butyl-6-methoxy-4-pentylquinolin-2(1H)-one (4e)
2-tert-Butoxy-3-butyl-5,7-dimethoxy-4-pentylquinoline (3m)
Yield: 65% (39 mg); colorless solid; mp 101.3–103.0 °C.
Yield: 45% (35 mg); yellow oil.
IR (film): 1646 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.91–0.98 (m, 6 H, CH3), 1.38–
1.55 (m, 10 H, CH2), 1.67 (s, 9 H, CH3), 2.64 (t, J = 7.6 Hz, 2 H,
CH2), 3.12 (t, J = 8.1 Hz, 2 H, CH2), 3.87–3.90 (m, 6 H, CH3), 6.35
(d, J = 2.5 Hz, 1 H, CH), 6.74 (d, J = 2.4 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): δ = 14.0, 14.2, 22.5, 23.1, 26.0, 28.8
(3CH3), 31.1, 31.2, 32.2, 32.8, 55.3, 55.4, 79.2, 96.2, 100.2, 111.6,
123.0, 147.5, 148.4, 158.0, 159.2, 160.9.
1H NMR (500 MHz, CDCl3): δ = 0.93–1.01 (m, 6 H, CH3), 1.39–
1.65 (m, 10 H, CH2), 2.76 (t, J = 7.4 Hz, 2 H, CH2), 2.85 (t,
J = 7.8 Hz, 2 H, CH2), 3.86 (s, 3 H, CH3), 7.07–7.11 (m, 2 H, CH),
7.32 (d, J = 8.8 Hz, 1 H, CH), 12.14 (s, 1 H, NH).
13C NMR (125 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.2, 26.9, 29.0,
29.4, 31.7, 32.4, 55.8, 107.1, 117.4 (2CH), 120.9, 131.8, 132.0,
146.8, 154.9, 163.6.
+
HRMS (ESI): m/z [M + H]+ calcd for C24H38NO3 : 388.2846; found:
388.2848.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2754–2762

2760
T. Meng et al.
PAPER
+
HRMS (ESI): m/z [M + H]+ calcd for C19H28NO2 : 302.2115; found:
302.2115.
1H NMR (300 MHz, CDCl3): δ = 0.95–1.06 (m, 6 H, CH3), 1.44–
1.69 (m, 10 H, CH2), 2.89–3.01 (m, 4 H, CH2), 7.60–7.88 (m, 5 H,
CH), 9.08 (t, J = 6.6 Hz, 1 H, CH), 12.76 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): δ = 14.05, 14.13, 22.5, 23.5, 27.2, 29.3,
29.9, 31.5, 32.4, 116.1, 121.8, 122.3, 122.5, 122.6, 126.4, 127.3,
128.1, 131.0, 133.2, 134.1, 148.5, 164.1.
6-Benzyl-3-butyl-4-pentylquinolin-2(1H)-one (4f)
Yield: 63% (46 mg); colorless solid; mp 124.4–126.2 °C.
IR (film): 1654 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.89–0.99 (m, 6 H, CH3), 1.31–
1.56 (m, 10 H, CH2), 2.71–2.83 (m, 4 H, CH2), 4.06 (s, 2 H, CH2),
7.18–7.33 (m, 7 H, CH), 7.41 (s, 1 H, CH), 12.12 (s, 1 H, NH).
HRMS (ESI): m/z [M + H]+ calcd for C22H28NO+: 322.2165; found:
322.2163.
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.4, 23.1, 26.7, 28.7,
29.6, 31.6, 32.2, 41.6, 116.4, 120.0, 124.1, 126.1, 128.5 (2CH),
128.9 (2CH), 130.0, 131.2, 134.7, 135.7, 141.0, 147.3, 163.9.
3-Butyl-4-pentyl-1,9-phenanthrolin-2(1H)-one (4k)
Yield: 43% (28 mg); colorless solid; mp 118.2–120.2 °C.
IR (film): 1643 (C=O) cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C25H32NO+: 362.2478; found:
362.2482.
1H NMR (500 MHz, CDCl3): δ = 0.97 (t, J = 7.3 Hz, 3 H), 1.04 (t,
J = 7.2 Hz, 3 H), 1.42–1.70 (m, 10 H), 2.89 (t, J = 7.9 Hz, 2 H),
3.02 (t, J = 8.2 Hz, 2 H), 7.74 (d, J = 8.9 Hz, 1 H), 7.88 (d,
J = 8.9 Hz, 1 H), 8.73 (d, J = 5.9 Hz, 1 H), 8.88 (d, J = 5.9 Hz, 1 H),
9.28 (s, 1 H), 13.00 (br, 1 H, NH).
13C NMR (125 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 23.4, 27.3, 29.3,
29.9, 31.5, 32.3, 115.1, 119.0, 121.4, 123.4, 126.2, 127.8, 132.7,
133.6, 144.3, 148.6, 152.1, 164.1.
3-Butyl-8-isopropyl-4-pentylquinolin-2(1H)-one (4g)
Yield: 73% (46 mg); colorless solid; mp 114.3–115.8 °C.
IR (film): 1630 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.92–0.99 (m, 6 H, CH3), 1.34–
1.62 (m, 16 H, CH2, CH3), 2.72 (t, J = 6.2 Hz, 2 H, CH2), 2.87 (t,
J = 6.6 Hz, 2 H, CH2), 3.43–3.51 (m, 1 H, CH), 7.16–7.20 (m, 1 H,
CH), 7.38 (t, J = 5.4 Hz, 1 H, CH), 7.56 (t, J = 6.3 Hz, 1 H, CH),
10.08 (s, 1 H, NH).
HRMS (ESI): m/z [M + H]+ calcd for C21H27N2O+: 323.2118; found:
323.2120.
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 22.5, 22.9 (2CH3), 23.3,
26.6, 27.0, 29.1, 29.7, 31.5, 32.4, 120.1, 121.8, 122.3, 125.3, 130.9,
133.4, 134.3, 147.7, 163.1.
3-Butyl-5,8-dimethoxy-4-pentylquinolin-2(1H)-one (4l)
Yield: 63% (42 mg); colorless solid; mp 130.3–132.1 °C.
IR (film): 1630 (C=O) cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C21H32NO+: 314.2478; found:
314.2479.
1H NMR (500 MHz, CDCl3): δ = 0.92–0.98 (m, 6 H, CH3), 1.37–
1.56 (m, 10 H, CH2), 2.70 (t, J = 7.8 Hz, 2 H, CH2), 3.07 (t,
J = 7.8 Hz, 2 H, CH2), 3.85 (s, 3 H, CH3), 3.90 (s, 3 H, CH3), 6.52
(d, J = 8.8 Hz, 1 H, CH), 6.81 (d, J = 8.8 Hz, 1 H, CH), 9.18 (s, 1 H,
NH).
13C NMR (125 MHz, CDCl3): δ = 14.04, 14.15, 22.5, 23.2, 26.5,
30.5, 31.7, 31.9, 32.7, 55.8, 56.3, 102.4, 108.8, 111.6, 128.9, 132.1,
139.8, 148.8, 151.4, 161.5.
3-Butyl-8-methoxy-4-pentylquinolin-2(1H)-one (4h)
Yield: 81% (49 mg); colorless solid; mp 113.2–115.1 °C.
IR (film): 1633 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.91–0.98 (m, 6 H, CH3), 1.36–
1.64 (m, 10 H, CH2), 2.70 (t, J = 7.8 Hz, 2 H, CH2), 2.84 (t,
J = 8.1 Hz, 2 H, CH2), 3.95 (s, 3 H, CH3), 6.91 (d, J = 7.8, 1 H, CH),
7.12 (t, J = 8.3, 1 H, CH), 7.27 (d, J = 8.4, 1 H, CH), 9.15 (s, 1 H,
NH).
+
HRMS (ESI): m/z [M + H]+ calcd for C20H30NO3 : 332.2220; found:
332.2222.
13C NMR (75 MHz, CDCl3): δ = 14.00, 14.02, 22.4, 23.1, 26.9, 29.1,
29.6, 31.5, 32.3, 55.9, 108.5, 116.4, 120.4, 121.4, 127.2, 132.2,
145.5, 147.1, 161.8.
3-Butyl-5,7-dimethoxy-4-pentylquinolin-2(1H)-one (4m)
Yield: 63% (42 mg); colorless solid; mp 166.8–168.3 °C.
IR (film): 1600 (C=O) cm–1.
+
HRMS (ESI): m/z [M + H]+ calcd for C19H28NO2 : 302.2115; found:
302.2114.
1H NMR (500 MHz, CDCl3): δ = 0.92–0.98 (m, 6 H, CH3), 1.38–
1.56 (m, 10 H, CH2), 2.71 (t, J = 7.8 Hz, 2 H, CH2), 3.05 (t,
J = 7.7 Hz, 2 H, CH2), 3.86–3.87 (m, 6 H, CH3), 6.24 (d, J = 2.3 Hz,
1 H, CH), 6.51 (t, J = 2.5 Hz, 1 H, CH), 12.34 (s, 1 H, NH).
13C NMR (125 MHz, CDCl3): δ = 14.0, 14.2, 22.6, 23.2, 26.1, 30.6,
31.9 (2CH2), 32.7, 55.3, 55.5, 91.2, 94.7, 106.1, 127.7, 140.7, 149.6,
158.6, 160.7, 164.1.
3-Butyl-4-pentyl-8-phenylquinolin-2(1H)-one (4i)
Yield: 70% (49 mg); yellow oil.
IR (film): 1640 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): δ = 0.96 (t, J = 7.2 Hz, 6 H, CH3),
1.41–1.55 (m, 8 H, CH2), 1.63–1.70 (m, 2 H, CH2), 2.70 (t,
J = 7.8 Hz, 2 H, CH2), 2.91 (t, J = 8.3 Hz, 2 H, CH2), 7.25 (t,
J = 7.8 Hz, 1 H, CH), 7.34 (d, J = 7.3 Hz, 1 H, CH), 7.40–7.41 (m,
2 H, CH), 7.45 (t, J = 7.4 Hz, 1 H, CH), 7.51 (t, J = 7.3 Hz, 2 H,
CH), 7.70 (d, J = 8.2 Hz, 1 H, CH), 8.67 (s, 1 H, NH).
+
HRMS (ESI): m/z [M + H]+ calcd for C20H30NO3 : 332.2220; found:
332.2222.
(Z)-(1-Bromopent-1-en-3-yne-1,2-diyl)dibenzene (5)24
Yield: 70% (884 mg); yellow solid; mp 83.2–84.9 °C.
13C NMR (125 MHz, CDCl3): δ = 14.0 (2CH3), 22.5, 23.1, 26.9,
29.1, 29.7, 31.5, 32.4, 120.4, 121.8, 124.1, 128.5, 128.6, 129.4
(2CH), 129.5 (2CH), 129.9, 131.7, 134.1, 136.5, 147.3, 162.2.
HRMS (ESI): m/z [M + H]+ calcd for C24H30NO+: 348.2322; found:
348.2322.
1H NMR (500 MHz, CDCl3): δ = 2.11 (s, 3 H, CH3), 7.12–7.19 (m,
10 H, CH).
13C NMR (125 MHz, CDCl3): δ = 4.9, 81.8, 93.7, 126.7, 127.4,
127.9 (2CH), 128.0 (2CH), 128.2, 128.3, 129.4 (2CH), 130.1
(2CH), 138.2, 139.5.
HRMS (ESI): m/z [M + H]+ calcd for C17H14Br+: 297.0273; found:
297.0277.
3-Butyl-4-pentylbenzo[h]quinolin-2(1H)-one (4j)
Yield: 71% (46 mg); colorless solid; mp 165.3–167.0 °C.
IR (film): 1636 (C=O) cm–1.
Pd-Catalyzed Amination of Monohaloenyne 5 Affording Quin-
oline 6 and Pyrrole 7
[Pd2(dba)3] (4.6 mg, 0.005 mmol), DPEPhos (10.8 mg, 0.02 mmol),
and toluene (2.0 mL) were placed in an oven-dried 25 mL Schlenk
Synthesis 2012, 44, 2754–2762
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of Quinolines and Quinolinones
2761
tube, and the mixture was stirred at r.t. for 15 min, then monohalo-
enyne 5 (59 mg, 0.2 mmol), aniline 2a (22 mg, 0.24 mmol), and
NaOt-Bu (58 mg, 0.6 mmol) were added. The tube was placed in a
preheated oil bath (110 °C) and stirred for 2 h. After cooling to r.t.,
the solvent was evaporated in vacuo and the crude product was pu-
rified by column chromatography over silica gel (EtOAc–pentane,
1→10%).
32.5, 79.5, 123.1, 123.5, 124.3, 125.6, 127.5, 128.0, 145.2, 145.8,
145.9, 160.5.
HRMS (ESI): m/z [M + H]+ calcd for C22H34NO+: 328.2635; found:
328.2638.
HRMS (ESI): m/z [M + H]+ calcd for C22H33DNO+: 329.2698;
found: 329.2701.
4-Ethyl-2,3-diphenylquinoline (6)
Yield: 57% (35 mg); yellow solid; mp 68.8–70.2 °C.
Acknowledgment
1H NMR (300 MHz, CDCl3): δ = 1.22 (t, J = 7.4 Hz, 3 H), 2.97 (q,
J = 7.2 Hz, 2 H), 7.11–7.31 (m, 10 H), 7.56–7.74 (m, 2 H), 8.09–
8.23 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 15.2, 22.6, 124.1, 125.9, 126.4,
126.9, 127.3, 127.5 (2CH), 127.9 (2CH), 129.0, 129.6 (2CH), 130.5
(3CH), 133.4, 138.8, 141.3, 147.3, 148.1, 159.0.
This work was supported by the Natural Science Foundation of Chi-
na and the Major State Basic Research Development Program
(2011CB808601).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
HRMS (ESI): m/z [M + H]+ calcd for C23H20N+: 310.1590; found:
310.1590.
References
5-Methyl-1,2,3-triphenyl-1H-pyrrole (7)
Yield: 16% (10 mg); yellow solid; mp 88.7–90.2 °C.
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13C NMR (125 MHz, CDCl3): δ = 13.1, 108.0, 122.5, 125.2, 126.5,
127.3, 127.8 (2CH), 128.1 (2CH), 128.2 (2CH), 128.6 (2CH), 128.7
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310.1592.
Control Experiment Confirming the Etherification
[Pd2(dba)3] (4.6 mg, 0.005 mmol), DPEPhos (10.8 mg, 0.02 mmol),
and toluene (2.0 mL) were placed in an oven-dried 25 mL Schlenk
tube, and the mixture was stirred at r.t. for 15 min, then 2-bromo-
quinoline 9 (42 mg, 0.2 mmol) and NaOt-Bu (58 mg, 0.6 mmol)
were added. The tube was placed in a preheated oil bath (110 °C)
and stirred for 2 h. After cooling to r.t., the solvent was evaporated
under vacuum and the residue was purified by chromatography
(EtOAc–pentane, 10→100%) to give quinoline 10 and quinolinone
11.
2-tert-Butoxyquinoline (10)25
Yield: 70% (28 mg); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.70 (s, 9 H, CH3), 6.79 (d,
J = 8.7 Hz, 1 H, CH), 7.32 (s, 1 H, CH), 7.57 (s, 1 H, CH), 7.65 (d,
J = 8.4 Hz, 1 H, CH), 7.79 (d, J = 8.4 Hz, 1 H, CH), 7.89 (d,
J = 8.7 Hz, 1 H, CH).
13C NMR (75 MHz, CDCl3): δ = 28.6 (3CH3), 80.1, 115.0, 123.6,
124.5, 127.2, 127.5, 129.0, 138.0, 146.4, 161.8.
Quinolin-2(1H)-one (11)26
Yield: 21% (6 mg); colorless solid.
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1H NMR (400 MHz, CDCl3): δ = 6.74 (d, J = 9.4 Hz, 1 H, CH),
7.20–7.24 (m, 1 H, CH), 7.47–7.57 (m, 3 H, CH), 7.83 (d,
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1H NMR (500 MHz, CDCl3): δ = 0.92–0.99 (m, 6 H, CH3), 1.38–
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