Facile three-component synthesis of substituted quinolines catalyzed by iridium(III) complex

Article abstract of DOI:10.1246/bcsj.79.1941

A convenient and efficient synthesis of substituted quinolines via a simple one-pot reaction of an aniline, an aromatic aldehyde, and an enolizable aliphatic aldehyde in the presence of the iridium catalyst [IrCl ₂H(cod)]₂ under oxygen as an oxidant was developed. The reaction proceeds with Mannich-type imine formation followed by nucleophilic addition to give β-amino aldehydes. Dehydrative cyclization takes place to give dihydroquinoline, which is then dehydrogenated by aerobic oxidation to give 2-aryl-3-alkylquinolines. Dialkylquinolines were obtained by the reaction with anilines and aliphatic aldehydes in good yields.

Full text of DOI:10.1246/bcsj.79.1941

Ó 2006 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 79, No. 12, 1941–1949 (2006) 1941
Facile Three-Component Synthesis of Substituted Quinolines
Catalyzed by Iridium(III) Complex
ꢀ
Takayuki Nakajima, Takashi Inada, Takeyuki Igarashi, Tadashi Sekioka, and Isao Shimizu
Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University,
3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555
Received May 16, 2006; E-mail: shimizui@waseda.jp
A convenient and efficient synthesis of substituted quinolines via a simple one-pot reaction of an aniline, an aro-
matic aldehyde, and an enolizable aliphatic aldehyde in the presence of the iridium catalyst [IrCl2H(cod)]2 under oxygen
as an oxidant was developed. The reaction proceeds with Mannich-type imine formation followed by nucleophilic
addition to give ꢀ-amino aldehydes. Dehydrative cyclization takes place to give dihydroquinoline, which is then dehy-
drogenated by aerobic oxidation to give 2-aryl-3-alkylquinolines. Dialkylquinolines were obtained by the reaction with
anilines and aliphatic aldehydes in good yields.
Designing and synthesizing functionalized compounds or
materials are essential for innovation in industrial technology.
Quinolines are one of the most used heterocyclic compounds
for functionalized materials, and substituted quinolines have
a wide variety of applications, such as pharmaceutical agents
and organic electroluminescence materials. Several synthetic
methods of quinolines are known; for example, Skraup,1
Dobner–von Miller,2 Friedlander,3 and Pfitzinger4 syntheses
the dehydrogenation step may be better under aerobic condi-
tions, instead of under inert atmospheres. In the course of
our studies, we have found that the reaction proceeds more
effectively under air or oxygen.8 Furthermore, the reaction
was found to proceed using [IrCl2H(cod)]2 as a catalyst with
much higher reactivity than [IrCl(cod)]2. We describe, here,
the details of the iridium(III)-catalyzed quinoline synthesis.
¨
¨
Results and Discussion
are recognized as fundamental methods. However, applicabil-
ity of these classical methods is limited to simple quinolines
without functional groups because a large amount of acids or
bases are necessary. Therefore, for preparation of functional-
ized quinolines, appropriate functional groups are introduced
to preexisting quinoline rings. In contrast, recently several
quinoline syntheses under mild conditions using transition
metals5 or Lewis acids6 have been reported. We have focused
on convergent methods, which involve the coupling of func-
tionalized moieties, because it is possible to prepare chemical-
ly diverse quinolines.
Previously, we reported a novel substituted quinoline syn-
thesis by the reaction of an aniline, an aromatic aldehyde,
and an aliphatic aldehyde in the presence of iridium catalysts,
such as [Ir(cod)Cl]2 (Scheme 1).7 The formation of the quino-
lines is considered to proceed via a Mannich reaction (A ! B)
followed by aromatic substitution and dehydration to form di-
hydroquinoline C, and finally, dehydrogenation of C proceeds
to afford quinolines as shown in Scheme 2. The final dehydro-
genation step seems to proceed either via a hydrogen-transfer
mechanism with hydrogen acceptors or an autoxidation mech-
anism. If the reaction proceeds via an autoxidation mechanism,
Optimization of the Iridium-Catalyzed Reaction with
Aniline, Benzaldehyde, and Butanal Using Dehydrogenat-
ing Agents. The results of the reactions with [IrCl2H(cod)]2
under various atmospheres are summarized in Table 1. A mix-
ture of aniline (1a) and benzaldehyde (5a) in DMSO was stir-
red in the presence of the iridium catalyst at room temperature
for 1 h, and then butanal (3a) was added. The resulting mixture
was heated at 90 ꢁC for 12 h under argon to give the desired
product 6a in 46% yield along with 3-ethyl-2-propylquinoline
(7a) and N-benzylaniline (8a) in 18 and 31% yields, respec-
tively (Entry 1). Amine 8a was considered to form from N-
benzylideneaniline intermediate 10a by hydrogen transfer with
the dihydroquinoline C. This hydrogen transfer was found to
proceed without catalysts under argon in an NMR tube. In-
deed, the reaction of the 1,2-dihydroquinoline 9,9 as a model
compound of the dihydroquinoline C, and the imine 10a pro-
ceeded to give 2-phenylquinoline (6b) and secondary amine 8a
(Scheme 3). In other words, a more efficient dehydrating agent
is needed to prevent the secondary amine formation.
We examined the reaction with several dehydrating agents,
such as nitrobenzene and 2,3-dichloro-5,6-dicyano-1,4-benzo-
NH2
R3
O
O
Ir cat.
R3
+
+
H
R2
H
-H2, H2O
N
R2
R1
R1
1
2
3
4
Scheme 1. Iridium-catalyzed three component coupling reaction.
Published on the web December 13, 2006; doi:10.1246/bcsj.79.1941

1942 Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006)
Facile Synthesis of Substituted Quinolines
H
O
R3
NH2
O
H
Ir cat.
O
+
R2
N
R2
H
R1
- H2O
R1
R3
N
Ir
R2
R1
H
1
2
A (imine)
3
Ir
O
OH
O
R3
R2
R3
R2
R3
Ir cat.
N
R1
N
H
R1
N
R2
R1
H
H
(
β
-amino aldehyde)
B
R3
R2
R3
R2
-H2
- H2O
R1
N
N
R1
H
C (1,2-dihydroquinoline)
4
Scheme 2. Plausible mechanism for quinoline synthesis.
Table 1. Three Component Coupling Reaction under Various Atmospheres
NH2
CHO
[IrCl2H(cod)]2 (2.5 mol%)
O
+
+
H
DMSO, 90 °C, 12 h
1a
5a
3a
N
N
N
+
+
H
6a
7a
8a
Yield/%aÞ
Entry
Cat.
Condition
6a
7a
8a
1
2
3
4
5
[IrCl2H(cod)]2
Under Argon
Under Air
Under O2
Under O2
Under O2
46
51
79
38
63
18
22
8
28
31
25
Trace
Trace
Trace
[IrCl(cod)]2
HCl
Trace
a) Isolated yield based on aniline 1a.
+
+
8a
(36 %)
N
H
N
N
DMSO-d6, 90 °C, 12 h
argon
9
10a
6b
(41 %)
Scheme 3.
quinone (DDQ), but these organic oxidants were not effec-
tive.10 However, the reaction was somewhat improved when
performed in air to give 6a (51%), 7a (22%), and 8a (25%).8a
Oxygen proved to give the best yield of 6a (79%) and a small
amount of 7a (8%). However, the IrI complex [IrCl(cod)]2
gave low yields even under O2. The optimal conditions, Entry
3 in Table 1, were employed in the most of the syntheses for a
wide variety of quinolines in this paper. During our investiga-
tions, another synthetic method involving the reaction of
imines and aldehydes in DMSO under acidic conditions was
reported by Baba et al.8a The method was applied to this reac-
tion to give the same product 6a in 63% yield (Entry 5).
Synthesis of Various 2-Arylquinolines. A wide range of
functionalized anilines, aromatic aldehydes, and aliphatic alde-
hydes were subjected to the procedure to synthesize the corre-
sponding quinolines in yields as shown in Table 2. Functional
groups, such as halogen, ester, methyl ether, and cyano, were
used. The yield of quinoline in the case of acetaldehyde was

T. Nakajima et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006) 1943
Table 2. Iridium-Catalyzed Synthesis of 2-Arylquinolines 6 from Anilines 1, Aromatic Aldehydes 5, and
Aliphatic Aldehydes 3
NH2
CHO
R3
[IrCl2H(cod)]2 (2.5 mol%)
O
R3
+
+
H
DMSO, 90 °C, 12 h
N
R1
R1
R2
O2 (1 atm)
1
5
3
6
R2
Product (Yield)a)
N
N
N
6a (79%)
6b (28%)
6c (63%)
Br
Bn
N
N
N
CO2Me
CN
6d (65%)
6e (63%)
6f (48%)
MeO2C
O
O
N
N
N
OMe
Br
6g (52%)
6h (38%)
6i (22%)
NC
MeO2C
F
N
N
N
O
F
MeO
6j (69%)
6k (54%)
6l (55%)
a) Isolated yield based on the aniline 1.
Table 3. Iridium-Catalyzed Synthesis of 2-Arylquinolines 6 from Imines 10 and Aliphatic Aldehydes 3
R3
R3
R3
[IrCl2H(cod)]2 (2.5 mol%)
O
R3
+
+
N
R1
DMSO, 90 °C, 12 h
H
N
R1
N
R1
R2
air
R2
10
3
6
7
Entry
Imines 10
R3
6 (Yield/%)aÞ
7 (Yield/%)aÞ
1
2
3
4
5
6
7
8
9
10
10a (R1 = R2 = H)
H
Me
Et
i-Pr
Me
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
6b (25)
6m (52)
6a (43)
6c (53)
6n (21)
6o (32)
6p (14)
6q (48)
6r (55)
6d (49)
7b (18)
7c (25)
7a (8)
7d (27)
7e (35)
7f (42)
7f (46)
7f (35)
7g (35)
7d (26)
10a
10a
10a
10b (R1 = p-OMe, R2 = H)
10b
10c (R1 = p-OMe, R2 = p-OMe)
10d (R1 = p-OMe, R2 = p-CO2Me)
10e (R1 = p-CO2Me, R2 = H)
10f (R1 = H, R2 = p-CO2Me)
a) Isolated yield based on the imine 10.
low, and oily polymeric by-products were formed. Other ali-
phatic aldehydes could be used, and 3-substituted quinolines
were obtained in satisfactory yields.
Reaction of Imine and Aliphatic Aldehyde. The other
crucial problem for the substituted quinoline synthesis was for-
mation of the by-product dialkylquinoline 7. To avoid dialkyl-
quinoline formation, a two step synthesis was examined.8a,8b
The reaction of aliphatic aldehyde 3 and the imine 10, obtained
from an aromatic aldehyde and an aniline, was carried out.
However, 2,3-dialkylquinolines 7 still formed in considerable
yields along with the desired quinolines 6 as shown in Table 3.
This results indicate that iridium-catalyzed hydrolysis of imine
10 occurred in the reaction. Actually, when N-benzylideneani-
line in DMSO-d6 was added to an NMR tube in the presence of
a catalytic amount of iridium catalyst (2.5 mol %), hydrolysis
of the imine to form an aldehyde was observed by using

1944 Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006)
Facile Synthesis of Substituted Quinolines
[IrCl2H(cod)]2 (2.5 mol%)
O
O
+
+
6d + 7d
(49%) (26%)
+
+
10f
10f
N
H
H
H
DMSO, 90 °C, 12 h
CO2Me
air
11
(20%)
[IrCl2H(cod)]2 (2.5 mol%)
+
6d
7d
11
DMSO, 90 °C, 12 h
(68%) (23%) (Trace)
O2 (1 atm)
Scheme 4.
Table 4. Iridium-Catalyzed Synthesis of Substituted Quinolines 7 from Anilines 1 and Aliphatic
Aldehydes 3
NH2
R2
R2
[IrCl2H(cod)]2 (2.5 mol%)
O
R2
+
DMSO, 90 °C, 12 h
H
R1
N
R1
air
1
3
7
Entry
R1
R2
7 (Yield/%)aÞ
Entry
R1
R2
7 (Yield/%)aÞ
1
2
3
4
5
6
7
H
Et
Et
Et
Et
Et
Et
Et
7a (59)
7h (55)
7i (53)
7j (41)
7k (55)
7l (17)
7m (68)
8
9
p-MeO
p-MeO
p-MeO
p-MeO
p-MeO
H
H
7n (41)
7e (47)
7o (49)
7f (83)
7f (81)bÞ
7d (>99)
7p (40)cÞ
o-MeO
p-MeO
o-F
p-F
o-CO2Et
p-CO2Me
Me
n-Pr
i-Pr
i-Pr
i-Pr
i-Pr
10
11
12
13
14
m-MeO
a) Isolated yield based on the aniline 1. b) The reaction was carried out at rt. c) The ratio of
5- and 7-isomers was 1:9.
1H NMR spectroscopy. Even the addition of drying agents,
lines were obtained in moderate yields (Entries 1–7), except
for ethyl 2-aminobenzoate (17%). In the case of the reaction
of 2-aminobenzoate the starting aniline was recovered, which
can be explained by steric effects of the ester group at the ortho
position. Next, several aliphatic aldehydes were used for 6-me-
thoxyquinoline from p-methoxyaniline (Entries 8–11). With 3-
methylaldehyde, the corresponding quinoline 7f was obtained
in high yield (Entry 11). When p-anisidine and 3-methylalde-
hyde were used even at room temperature, quinoline 7f was
obtained in high yield (Entry 12). The reaction of m-anisidine
with 3-methylaldehyde afforded a 1:9 mixture of 5- and 7-iso-
mers (7p and 7p0), which is a similar selectivity to the rho-
dium-catalyzed reaction at 180 ꢁC reported by Watanabe and
co-workers.5a
such as MgSO4 or molecular sieves, did not increase the selec-
tivity. Compared with the results in Table 2, the yields of quin-
olines 6a and 6c prepared by the reaction of 10 and 3 (Entries 3
and 4 in Table 3) were lower than those by the reaction of 1, 5,
and 3 (Table 2), which is explained by the different ratio of
aromatic imines 10 that formed in situ in the reaction of the
aromatic aldehydes and anilines under the three-component
coupling reaction conditions.
In the reaction of imine 10f and 3-methylbutanal, 1,2-di-
alkylquinoline 7d was obtained along with quinoline 6d as
normal; however, a considerable amount of 11 (20%) was
obtained (Scheme 4). Dihydroquinoline 11 was oxidized into
quinoline 6d slowly in air, which indicates that the methoxy-
carbonyl substituent at the para position decreases the rate of
the autoxidation from 11 to 6d. However, the reaction under
oxygen proceeded smoothly to give 6d in good yield (68%),
and the dihydroquinoline 11 was almost completely oxidized.
Synthesis of 2,3-Dialkylquinolines. It is difficult to syn-
thesize 2,3-dialkylquinolines using two different aliphatic
aldehydes. However, the iridium-catalyzed three-component
coupling reaction with two equivalents of an aliphatic alde-
hyde gives 2,3-dialkylquinolines in moderate to good yields.
Reaction of aniline 1 (1 mmol) and aliphatic aldehyde 3 (2.5
mmol) in the presence of a catalytic amount of [IrCl2H(cod)]2
at 90 ꢁC for 12 h under an air atmosphere afforded 2,3-dialkyl-
substituted quinolines 7 as shown in Table 4. Reaction of var-
ious substituted anilines 1, such as anisidine and fluoroaniline,
with propanal was carried out, and the corresponding quino-
Conclusion
In summary, we have developed an efficient and general
route to substituted quinolines via a one-pot synthesis from
an aniline, an aromatic aldehyde, and an aliphatic aldehyde
in the presence of a catalytic amount of an iridium(III) com-
plex under aerobic conditions. This reaction is a promising
method to prepare various functional quinolines. Further de-
velopment is underway.
Experimental
1H NMR and 13C NMR spectra were recorded in CDCl3 as a
solvent using TMS as an internal standard on a JEOL Lambda
500 spectrometer. Multiplicities are indicated as br (broadened),
s (singlet), d (doublet), t (triplet), q (quartet), and m (multiplet).

T. Nakajima et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006) 1945
High-resolution mass spectroscopy (HRMS) and elemental anal-
ysis were performed by the Material Characterization Central
Laboratory of Waseda University.
(OCH3), 126.6, 127.1, 127.9, 128.9, 129.1, 129.2, 129.6, 129.7,
133.0, 140.0, 145.5, 146.1, 159.2 (aromatic C), 166.9 (CO);
HRMS (FAB) calcd for C20H20NO2 ½M þ Hꢃþ 306.1494, found
306.1461; Anal. Calcd for C20H19NO2: C, 78.66; H, 6.27; N,
4.59%. Found: C, 78.66; H, 6.46; N, 4.41%.
6-Bromo-2-(4-cyanophenyl)-3-ethylquinoline (6e) (Table 2):
White solid (212 mg, 63%); 1H NMR (500 MHz, CDCl3) ꢁ 1.20 (t,
J ¼ 7:5 Hz, 3H, CH3), 2.77 (q, J ¼ 7:5 Hz, 2H, CH2), 7.67 (d,
J ¼ 8:1 Hz, 2H, aromatic H), 7.75 (dd, J ¼ 9:0, 2.2 Hz, 1H, aro-
matic H), 7.79 (d, J ¼ 8:2 Hz, 2H, aromatic H), 7.95 (d, J ¼ 9:0
Hz, 1H, aromatic H), 7.99 (m, 2H, aromatic H); 13C NMR (125
MHz, CDCl3) ꢁ 14.6 (CH3), 25.8 (CH2), 112.2 (aromatic C),
118.6 (CN), 121.0, 129.0, 129.1, 129.6, 131.0, 132.2, 132.8, 134.5,
135.8, 144.9, 145.0, 158.7 (aromatic C); HRMS (FAB) calcd for
C18H14BrN2 ½M þ Hꢃþ 337.0340, found 337.0346; Anal. Calcd
for C18H13BrN2: C, 64.11; H, 3.89; N, 8.31%. Found: C, 64.01;
H, 4.21; N, 7.84%.
General Procedure for the Reaction of Aniline (1a), Benzal-
dehyde (2a), and Butanal (3a) in Table 1. A mixture of aniline
(1a) (1.0 mmol), benzaldehyde (2a), (2.0 mmol), and [IrCl2H-
(cod)]2 (0.025 mmol) in DMSO (3 mL) was stirred at room tem-
perature for 1 h, and butanal (3a) (1.5 mmol) was added to the
mixture. After the resulting mixture was stirred at 90 ꢁC for
12 h, the mixture was washed with phosphate buffer saline
(PBS, 50 mL) and extracted with AcOEt (20 mL ꢂ 3). The organ-
ic layer was dried over MgSO4. Removal of the solvent in vacuo,
followed by chromatographic purification on silica gel (AcOEt/
Hexane = 5/95) afforded 6a, 7a, and 8a.
General Procedure for the Synthesis of 2-Arylquinolines 6 in
Table 2. A mixture of an aniline 1 (1.0 mmol), an aromatic alde-
hyde 2 (2.0 mmol), and [IrCl2H(cod)]2 (0.025 mmol) in DMSO
(3 mL) was stirred at room temperature for 1 h, and an aliphatic al-
dehyde 3 (1.5 mmol) was added to the mixture. After the resulting
mixture was stirred at 90 ꢁC under oxygen (1 atm) for 12 h, the
mixture was washed with PBS (50 mL) and extracted with AcOEt
(20 mL ꢂ 3). The organic layer was dried over MgSO4. Removal
of the solvent in vacuo, followed by chromatographic purification
on silica-gel column (AcOEt/Hexane = 5/95) afforded 6.
3-Ethyl-2-phenylquinoline (6a) (Table 2): Yellow oil (185
mg, 79%); 1H NMR (500 MHz, CDCl3) ꢁ 1.19 (t, J ¼ 7:5 Hz, 3H,
CH3), 2.80 (q, J ¼ 7:5 Hz, 2H, CH2), 7.42–7.56 (m, 6H, aromatic
H), 7.66 (td, J ¼ 7:7, 1.5 Hz, 1H, aromatic H), 7.81 (d, J ¼ 8:2
Hz, 1H, aromatic H), 8.05 (s, 1H, aromatic H), 8.13 (d, J ¼ 8:4
Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 14.7 (CH3),
26.0 (CH2), 126.3, 126.9, 127.7, 128.0, 128.3, 128.7, 128.7, 129.3,
134.9, 135.3, 140.9, 146.3, 160.6 (aromatic C); HRMS (FAB)
calcd for C17H16N ½M þ Hꢃþ 234.1283, found 234.1251.
3-Benzyl-2-phenylquinoline (6f) (Table 2): Yellow crystals
1
(143 mg, 48%); H NMR (500 MHz, CDCl3) ꢁ 4.05 (s, 2H, CH2),
6.91–6.92 (m, 2H, aromatic H), 7.10–7.17 (m, 3H, aromatic H),
7.34–7.37 (m, 3H, aromatic H), 7.39–7.43 (m, 3H, aromatic H),
7.60 (td, J ¼ 7:7, 1.5 Hz, 1H, aromatic H), 7.67 (dd, J ¼ 8:2,
1.1 Hz, 1H, aromatic H), 7.84 (s, 1H, aromatic H), 8.06 (d, J ¼
8:4 Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 39.1
(CH2), 126.2, 126.5, 127.1, 127.5, 128.2, 128.3, 128.5, 128.8,
129.0, 129.1, 129.3, 132.5, 137.0, 139.9, 140.6, 146.6, 160.7
(aromatic C); HRMS (FAB) calcd for C22H18N ½M þ Hꢃþ
296.1439, found 296.1433; Anal. Calcd for C22H17N: C, 89.46;
H, 5.80; N, 4.74%. Found: C, 89.33; H, 5.82; N, 4.51%.
2-(2-Bromophenyl)-3-ethyl-6-methoxycarbonylquinoline (6g)
1
(Table 2): Pale yellow oil (200 mg, 52%); H NMR (500 MHz,
CDCl3) ꢁ 1.11 (t, J ¼ 7:5 Hz, 3H, CH3), 2.46–2.48 (m, 1H, CH2),
2.59–2.61 (m, 1H, CH2), 3.89 (s, 3H, OCH3), 7.20–7.23 (m, 1H,
aromatic H), 7.27–7.29 (m, 1H, aromatic H), 7.33–7.36 (m, 1H,
aromatic H), 7.58 (d, J ¼ 8:1 Hz, 1H, aromatic H), 8.06–8.07 (m,
2H, aromatic H), 8.16 (dd, J ¼ 8:9, 1.5 Hz, 1H, aromatic H), 8.52
(s, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 13.8 (CH3),
25.3 (CH2), 52.3 (OCH3), 122.1, 127.1, 127.4, 128.0, 128.2, 129.4,
129.8, 130.0, 130.2, 132.6, 135.5, 136.5, 141.0, 147.8, 162.0
(aromatic C), 166.6 (CO); HRMS (FAB) calcd for C19H17BrNO2
½M þ Hꢃþ 370.0443, found 370.0443.
2-Phenylquinoline (6b) (Table 2): Colorless needles (58 mg,
1
28%); H NMR (500 MHz, CDCl3) ꢁ 7.45–7.48 (m, 1H, aromatic
H), 7.52–7.55 (m, 3H, aromatic H), 7.73 (td, J ¼ 6:8, 1.5 Hz, 1H,
aromatic H), 7.83 (dd, J ¼ 8:2, 1.1 Hz, 1H, aromatic H), 7.88 (d,
J ¼ 8:6 Hz, 1H, aromatic H), 8.16–8.18 (m, 3H, aromatic H), 8.22
(d, J ¼ 8:6 Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ
119.0, 126.3, 127.2, 127.4, 127.6, 128.8, 129.3, 129.6, 129.8,
136.7, 139.7, 148.3, 157.3 (aromatic C); HRMS (FAB) calcd for
C15H12N ½M þ Hꢃþ 206.0970, found 206.0978; Anal. Calcd for
C15H11N: C, 87.77; H, 5.40; N, 6.82%. Found: C, 87.60; H, 5.66;
N, 6.67%.
2-(3,4-Methylenedioxyphenyl)-3-propylquinoline
(6h)
1
(Table 2): Pale yellow oil (110 mg, 38%); H NMR (500 MHz,
CDCl3) ꢁ 0.87 (t, J ¼ 7:3 Hz, 3H, CH3), 1.54–1.59 (m, 2H, CH2),
2.76 (t, J ¼ 8:1 Hz, 2H, CH2), 6.00 (s, 2H, OCH2O), 6.90 (d, J ¼
7:9 Hz, 1H, aromatic H), 7.00–7.03 (m, 2H, aromatic H), 7.47–
7.50 (m, 1H, aromatic H), 7.62–7.65 (m, 1H, aromatic H), 7.76
(d, J ¼ 8:1 Hz, 1H, aromatic H), 7.98 (s, 1H, aromatic H), 8.09
(d, J ¼ 8:4 Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ
13.9 (CH3), 23.6, 34.9 (CH2), 101.0 (OCH2O), 108.1, 109.5,
122.5, 126.2, 126.8, 127.5, 128.7, 129.1, 133.8, 134.9, 135.7,
146.3, 147.4, 147.5, 160.1 (aromatic C); HRMS (FAB) calcd for
C19H18NO2 ½M þ Hꢃþ 292.1338, found 292.1327.
3-Isopropyl-2-phenylquinoline (6c) (Table 2): White solid
(155 mg, 63%); 1H NMR (500 MHz, CDCl3) ꢁ 1.25 (d, J ¼ 7:0
Hz, 6H, CH3), 3.23–3.26 (m, 1H, CH), 7.44–7.53 (m, 6H, aromat-
ic H), 7.65 (td, J ¼ 7:7, 1.1 Hz, 1H, aromatic H), 7.82 (d, J ¼ 8:1
Hz, 1H, aromatic H), 8.12 (m, 2H, aromatic H); 13C NMR (125
MHz, CDCl3) ꢁ 24.1 (CH3), 29.2 (CH), 126.3, 127.0, 127.8,
127.9, 128.2, 128.7, 128.8, 129.2, 132.7, 140.3, 141.0, 146.1,
160.4 (aromatic C); HRMS (FAB) calcd for C18H18N ½M þ Hꢃþ
248.1439, found 248.1432; Anal. Calcd for C18H17N: C, 87.41;
H, 6.93; N, 5.66%. Found: C, 86.84; H, 7.03; N, 5.49%.
3-Isopropyl-2-(4-methoxycarbonylphenyl)quinoline (6d)
3-Isopropyl-8-methoxy-2-(naphthalen-2-yl)quinoline (6i)
(Table 2):
White solid (80 mg, 22%); 1H NMR (500 MHz,
(Table 2):
Colorless crystals (200 mg, 65%); 1H NMR (500
CDCl3) ꢁ 1.24 (d, J ¼ 6:9 Hz, 6H, CH3), 3.28–3.34 (m, 1H, CH),
4.04 (s, 3H, OMe), 7.01 (d, J ¼ 7:3 Hz, 1H, aromatic H), 7.41–
7.47 (m, 2H, aromatic H), 7.51 (q, J ¼ 3:3 Hz, 2H, aromatic H),
7.66 (d, J ¼ 8:3 Hz, 1H, aromatic H), 7.89–7.92 (m, 3H, aromatic
H), 8.04 (s, 1H, aromatic H), 8.12 (s, 1H, aromatic H); 13C NMR
(125 MHz, CDCl3) ꢁ 24.1 (CH3), 29.3 (CH), 56.0 (OCH3), 107.0,
119.0, 126.1, 126.1, 126.5, 127.2, 127.5, 127.6, 128.3, 128.4,
MHz, CDCl3) ꢁ 1.25 (d, J ¼ 7:0 Hz, 6H, CH3), 3.17–3.19 (m,
1H, CH), 3.96 (s, 3H, OCH3), 7.54 (td, J ¼ 7:1, 0.7 Hz, 1H, aro-
matic H), 7.61 (d, J ¼ 8:2 Hz, 2H, aromatic H), 7.68 (td, J ¼ 7:0,
1.3 Hz, 1H, aromatic H), 7.83 (d, J ¼ 8:1 Hz, 1H, aromatic H),
8.11 (d, J ¼ 8:6 Hz, 1H, aromatic H), 8.15–8.18 (m, 3H, aromatic
H); 13C NMR (125 MHz, CDCl3) ꢁ 24.0 (CH3), 29.2 (CH2), 52.1

1946 Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006)
Facile Synthesis of Substituted Quinolines
129.0, 132.7, 132.9, 133.2, 138.2, 138.6, 141.1, 155.4, 159.0
(aromatic C); HRMS (FAB) calcd for C23H22NO ½M þ Hꢃþ
328.1693, found 328.1678; Anal. Calcd for C23H21NO: C, 84.37;
H, 6.46; N, 4.28%. Found: C, 84.29; H, 6.41; N, 4.34%.
yellow crystals (2.38 g, 99%); 1H NMR (500 MHz, CDCl3) ꢁ
3.82 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 6.92 (d, J ¼ 8:8 Hz, 2H,
aromatic H), 6.97 (d, J ¼ 8:6 Hz, 2H, aromatic H), 7.20 (d, J ¼
8:6 Hz, 2H, aromatic H), 7.83 (d, J ¼ 8:6 Hz, 2H, aromatic H),
8.40 (s, 1H, azomethine H); 13C NMR (125 MHz, CDCl3) ꢁ 55.4,
55.5 (OCH3), 114.1, 114.3, 122.0, 129.5, 130.2, 145.3, 157.8,
157.9 (aromatic C), 162.0 (azomethine C); HRMS (FAB) calcd
for C15H16NO2 ½M þ Hꢃþ 242.1181, found 242.1183; Anal. Calcd
for C15H15NO2: C, 74.67; H, 6.27; N, 5.81%. Found: C, 74.76; H,
6.30; N, 5.78%.
N-(4-Methoxycarbonylbenzylidene)-4-methoxyaniline (10d):
Pale yellow crystals (2.61 g, 97%); 1H NMR (500 MHz, CDCl3) ꢁ
3.84 (s, 3H, OCH3), 3.95 (s, 3H, CO2CH3), 6.94 (d, J ¼ 8:8 Hz,
2H, aromatic H), 7.27 (d, J ¼ 8:8 Hz, 2H, aromatic H), 7.95 (d,
J ¼ 8:2 Hz, 2H, aromatic H), 8.12 (d, J ¼ 8:2 Hz, 2H, aromatic
H), 8.53 (s, 1H, azomethine H); 13C NMR (125 MHz, CDCl3) ꢁ
52.2 (CO2CH3), 55.5 (OCH3), 114.4, 122.4, 128.3, 129.9, 131.9,
140.3, 144.3, 156.7 (aromatic C), 158.7 (azomethine C), 166.6
(CO2CH3); HRMS (FAB) calcd for C16H16NO3 ½M þ Hꢃþ
270.1130, found 270.1135; Anal. Calcd for C16H15NO3: C, 71.36;
H, 5.61; N, 5.20%. Found: C, 71.35; H, 5.55; N, 5.16%.
N-Benzylidene-4-methoxycarbonylaniline (10e): Colorless
crystals (1.43 g, 60%); 1H NMR (500 MHz, CDCl3) ꢁ 3.93 (s, 3H,
CO2CH3), 7.21 (d, J ¼ 8:2 Hz, 2H, aromatic H), 7.49–7.51 (m,
3H, aromatic H), 7.91 (d, J ¼ 6:8 Hz, 2H, aromatic H), 8.07
(d, J ¼ 8:2 Hz, 2H, aromatic H), 8.44 (s, 1H, azomethine H);
13C NMR (125 MHz, CDCl3) ꢁ 52.0 (CO2CH3), 120.7, 127.4,
128.9, 129.0, 130.9, 131.9, 135.8, 156.3 (aromatic C), 161.6
(s, azomethine C), 166.8 (CO2CH3); HRMS (FAB) calcd for
C15H14NO2 ½M þ Hꢃþ 240.1025, found 240.0994; Anal. Calcd
for C15H13NO2: C, 75.30; H, 5.48; N, 5.85%. Found: C, 75.25;
H, 5.46; N, 5.82%.
3-Ethyl-6-methoxycarbonyl-2-(2-methoxyphenyl)quinoline
1
(6j) (Table 2): Yellow oil (220 mg, 69%); H NMR (500 MHz,
CDCl3) ꢁ 1.15 (t, J ¼ 7:5 Hz, 3H, CH3), 2.56–2.58 (m, 1H,
CH2), 2.66–2.68 (m, 1H, CH2), 3.70 (s, 3H, OCH3), 3.95 (s, 3H,
OCH3), 6.96 (d, J ¼ 8:4 Hz, 1H, aromatic H), 7.04–7.08 (m, 1H,
aromatic H), 7.30 (dd, J ¼ 7:3, 1.3 Hz, 1H, aromatic H), 7.38–
7.41 (m, 1H, aromatic H), 8.06 (s, 1H, aromatic H), 8.13 (d, J ¼
8:8 Hz, 1H, aromatic H), 8.19–8.21 (m, 1H, aromatic H), 8.57
(s, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 13.9 (CH3),
25.1 (CH2), 52.2 (OCH3), 55.3 (OCH3), 110.8, 120.8, 127.0,
127.6, 127.9, 129.4, 129.6, 129.8, 130.1, 130.2, 134.6, 137.6,
148.1, 156.4, 161.3 (aromatic C), 166.8 (CO); HRMS (FAB) calcd
for C20H20NO3 ½M þ Hꢃþ 322.1443, found 322.1437.
6-Fluoro-2-(furan-2-yl)-3-isopropylquinoline (6k) (Table 2):
Yellow oil (138 mg, 54%); 1H NMR (500 MHz, CDCl3) ꢁ 1.25 (d,
J ¼ 6:8 Hz, 6H, CH3), 3.66–3.68 (m, 1H, CH), 6.50 (dd, J ¼ 3:5,
1.8 Hz, 1H, aromatic H), 6.94 (dd, J ¼ 3:5, 0.7 Hz, 1H, aromatic
H), 7.28–7.35 (m, 2H, aromatic H), 7.55 (m, 1H, aromatic H),
7.95 (s, 1H, aromatic H), 8.01 (dd, J ¼ 9:2, 5.3 Hz, 1H, aromatic
H); 13C NMR (125 MHz, CDCl3) ꢁ 23.7 (CH3), 28.8 (CH), 109.9
(d, JCF ¼ 21:0 Hz, aromatic C), 111.5, 111.8 (aromatic C), 119.2
(d, JCF ¼ 25:8 Hz, aromatic C), 128.2 (d, JCF ¼ 9:7 Hz, aromatic
C), 131.6 (d, JCF ¼ 8:9 Hz, aromatic C), 132.4 (d, JCF ¼ 5:6 Hz,
aromatic C), 140.7, 143.4 (aromatic C), 148.3 (d, JCF ¼ 3:2 Hz,
aromatic C), 153.5, 159.5, 161.5 (aromatic C); HRMS (FAB)
calcd for C16H15FNO ½M þ Hꢃþ 256.1138, found 256.1128; Anal.
Calcd for C16H14FNO: C, 75.28; H, 5.53; N, 5.49%. Found: C,
75.22; H, 5.83; N, 5.45%.
6-Cyano-2-(4-fluorophenyl)-3-isopropylquinoline
(6l)
N-(4-Methoxycarbonylbenzylidene)aniline (10f): Colorless
crystals (2.20 g, 92%); 1H NMR (500 MHz, CDCl3) ꢁ 3.94 (s,
3H, CO2CH3), 7.22–7.27 (m, 3H, aromatic H), 7.40 (t, J ¼ 7:5
Hz, 2H, aromatic H), 7.96 (d, J ¼ 7:9 Hz, 2H, aromatic H), 8.13
(d, J ¼ 8:1 Hz, 2H, aromatic H), 8.49 (s, 1H, azomethine H);
13C NMR (125 MHz, CDCl3) ꢁ 52.2 (CO2CH3), 120.9, 126.4,
128.6, 129.2, 129.9, 132.3, 140.0, 151.5 (aromatic C), 159.0 (azo-
methine C), 166.5 (CO2CH3); HRMS (FAB) calcd for C15H14NO2
½M þ Hꢃþ 240.1025, found 240.1016; Anal. Calcd for C15H13-
NO2: C, 75.30; H, 5.48; N, 5.85%. Found: C, 75.33; H, 5.45; N,
5.78%.
General Procedure for the Reaction of Imine 10 and Ali-
phatic Aldehyde 3 in Table 3. A mixture of an imine 10 (1.0
mmol), an aliphatic aldehyde 3 (1.5 mmol), and [IrCl2H(cod)]2
(0.025 mmol) in DMSO (3 mL) was stirred at 90 ꢁC for 12 h under
an air atmosphere. The resulting mixture was washed with PBS
(50 mL) and extracted with AcOEt (20 mL ꢂ 3). The organic
layer was dried over MgSO4. Removal of the solvent in vacuo,
followed by chromatographic purification on silica gel (AcOEt/
Hexane = 5/95) afforded 6 and 7.
3-Methyl-2-phenylquinoline (6m) (Table 3, Entry 2): Pale
yellow oil (114 mg, 52%); 1H NMR (500 MHz, CDCl3) ꢁ 2.45
(s, 3H, CH3), 7.42–7.56 (m, 4H, aromatic H), 7.41–7.60 (m, 2H,
aromatic H), 7.65 (td, J ¼ 7:7, 1.5 Hz, 1H, aromatic H), 7.77 (d,
J ¼ 8:1 Hz, 1H, aromatic H), 8.00 (s, 1H, aromatic H), 8.12 (d,
J ¼ 8:4 Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 20.6
(CH3), 126.3, 126.6, 127.5, 128.1, 128.2, 128.7, 128.8, 129.1,
129.3, 136.7, 140.8, 146.6, 160.5 (aromatic C); HRMS (FAB)
calcd for C16H14N ½M þ Hꢃþ 234.1283, found 234.1251.
6-Methoxy-3-methyl-2-phenylquinoline (6n) (Table 3, En-
1
(Table 2): Yellow crystals (160 mg, 55%); H NMR (500 MHz,
CDCl3) ꢁ 1.18 (d, J ¼ 6:8 Hz, 6H, CH3), 3.18–3.21 (m, 1H, CH),
7.10–7.13 (m, 2H, aromatic H), 7.43–7.45 (m, 2H, aromatic H),
7.71 (d, J ¼ 8:8 Hz, 1H, aromatic H), 8.07–8.10 (m, 2H, aromatic
H), 8.15 (s, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 23.9
(CH3), 29.3 (CH), 110.0 (CN), 111.4 (d, JCF ¼ 22:5 Hz, aromatic
C), 118.6, 127.1, 129.5, 130.5, 130.5 (aromatic C), 133.4 (d, JCF
¼
15:3 Hz, aromatic C), 135.9 (d, JCF ¼ 3:2 Hz, aromatic C), 142.4,
146.8, 161.9, 162.2, 163.9 (aromatic C); HRMS (FAB) calcd for
C19H16FN2 ½M þ Hꢃþ 291.1298, found 291.1303; Anal. Calcd
for C19H15FN2: C, 78.60; H, 5.21; N, 9.65%. Found: C, 78.39;
H, 5.11; N, 9.66%.
General Procedure for the Synthesis of Imines 10b–10f.
A
mixture of an aniline (10 mmol) and an aromatic aldehyde (15
mmol) in anhydrous MeOH (30 mL) was stirred at room temper-
ature. After 10 min, a yellow precipitate was formed. The precip-
itate was collected by filtration, and the filtrate was washed with
cold MeOH (10 mL ꢂ 3).
N-Benzylidene-4-methoxyaniline (10b): Colorless crystals
(1.47 g, 70%); 1H NMR (500 MHz, CDCl3) ꢁ 3.83 (s, 3H, OCH3),
6.93 (d, J ¼ 8:8 Hz, 2H, aromatic H), 7.23 (d, J ¼ 8:8 Hz, 2H,
aromatic H), 7.45–7.47 (m, 3H, aromatic H), 7.89 (m, 2H, aromat-
ic H), 8.48 (s, 1H, azomethine H); 13C NMR (125 MHz, CDCl3)
ꢁ 55.5 (OCH3), 114.4, 122.2, 128.6, 128.7, 131.0, 136.4, 144.9,
158.3 (aromatic C), 158.4 (azomethine C); HRMS (FAB) calcd
for C14H13NNaO ½M þ Naꢃþ 234.0895, found 234.0928; Anal.
Calcd for C14H13NO: C, 79.59; H, 6.20; N, 6.63%. Found: C,
79.61; H, 6.27; N, 6.60%.
N-(4-Methoxybenzylidene)-4-methoxyaniline (10c):
Pale

T. Nakajima et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006) 1947
try 5): Colorless crystals (52 mg, 21%); 1H NMR (500 MHz,
CDCl3) ꢁ 2.47 (s, 3H, CH3), 3.94 (s, 3H, OCH3), 7.04 (d, J ¼
2:6 Hz, 1H, aromatic H), 7.31 (dd, J ¼ 9:2, 2.6 Hz, 1H, aromatic
H), 7.40–7.43 (m, 1H, aromatic H), 7.46–7.49 (m, 2H, aromatic
H), 7.57 (d, J ¼ 7:5 Hz, 2H, aromatic H), 7.91 (s, 1H, aromatic
H), 8.01 (d, J ¼ 9:2 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 20.6 (CH3), 55.5 (OCH3), 104.2, 121.4, 128.0, 128.2,
128.5, 128.9, 129.4, 130.8, 135.6, 141.0, 142.7, 157.8, 158.0
(aromatic C); HRMS (FAB) calcd for C17H16NO ½M þ Hꢃþ
250.1232, found 250.1224; Anal. Calcd for C17H15NO: C, 81.90;
H, 6.06; N, 5.62%. Found: C, 81.88; H, 6.00; N, 5.53%.
crystals (43 mg, 25%); 1H NMR (500 MHz, CDCl3) ꢁ 1.37 (t,
J ¼ 7:5 Hz, 3H, CH3), 2.48 (s, 3H, CH3), 2.99 (q, J ¼ 7:5 Hz,
2H, CH2), 7.44 (m, 1H, aromatic H), 7.59–7.62 (m, 1H, aromatic
H), 7.69 (d, J ¼ 8:1 Hz, 1H, aromatic H), 7.82 (s, 1H, aromatic
H), 8.01 (d, J ¼ 8:4 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 12.8, 19.1 (CH3), 29.5 (CH2), 125.6, 126.6, 127.3,
128.2, 128.5, 129.4, 135.7, 146.7, 163.3 (aromatic C); HRMS
(FAB) calcd for C12H14N ½M þ Hꢃþ 172.1126, found 172.1099;
Anal. Calcd for C12H13N: C, 84.17; H, 7.65; N, 8.18%. Found:
C, 84.05; H, 7.65; N, 8.03%.
2-Isobutyl-3-isopropyl-6-methoxycarbonylquinoline (7g)
White crystals (99 mg, 35%); 1H NMR
3-Isopropyl-6-methoxy-2-phenylquinoline (6o) (Table 3,
Entry 6): White crystals (75 mg, 32%); 1H NMR (500 MHz,
CDCl3) ꢁ 1.23 (d, J ¼ 6:8 Hz, 6H, CH3), 3.21–3.24 (m, 1H, CH),
3.92 (s, 3H, OCH3), 7.08 (d, J ¼ 2:7 Hz, 1H, aromatic H), 7.31
(dd, J ¼ 4:6, 2.7 Hz, 1H, aromatic H), 7.40–7.51 (m, 5H, aromatic
H), 8.00–8.01 (m, 2H, aromatic H); 13C NMR (125 MHz, CDCl3)
ꢁ 24.1 (CH3), 29.2 (CH2), 55.4 (OCH3), 104.5, 121.6, 127.7,
128.2, 128.7, 128.8, 130.7, 131.5, 140.5, 141.1, 142.3, 157.7,
157.8 (aromatic C); HRMS (FAB) calcd for C19H20NO ½M þ
Hꢃþ 278.1545, found 278.1540; Anal. Calcd for C19H19NO: C,
82.28; H, 6.90; N, 5.05%. Found: C, 82.28; H, 7.09; N, 4.89%.
3-Isopropyl-6-methoxy-2-(4-methoxyphenyl)quinoline (6p)
(Table 3, Entry 7): White solid (43 mg, 14%); 1H NMR (500
MHz, CDCl3) ꢁ 1.24 (d, J ¼ 6:8 Hz, 6H, CH3), 3.25–3.30 (m, 1H,
CH), 3.87 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 7.01 (d, J ¼ 8:4 Hz,
2H, aromatic H), 7.08 (d, J ¼ 2:7 Hz, 1H, aromatic H), 7.31 (dd,
J ¼ 9:2, 2.7 Hz, 1H, aromatic H), 7.46 (d, J ¼ 8:2 Hz, 2H, aro-
matic H), 7.98–8.00 (m, 2H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 24.2 (CH3), 29.2 (CH2), 55.4, 55.5 (OCH3), 104.5,
113.7, 121.5, 128.6, 130.1, 130.6, 131.5, 133.6, 140.7, 142.4,
157.6, 157.6, 159.4 (aromatic C); HRMS (FAB) calcd for
C20H22NO2 ½M þ Hꢃþ 308.1651, found 308.1653; Anal. Calcd
for C20H21NO2: C, 78.15; H, 6.89; N, 4.56%. Found: C, 78.17;
H, 6.97; N, 4.38%.
3-Isopropyl-6-methoxy-2-(4-methoxycarbonylphenyl)quino-
line (6q) (Table 3, Entry 8): Colorless crystals (161 mg, 48%);
1H NMR (500 MHz, CDCl3) ꢁ 1.24 (d, J ¼ 7:0 Hz, 6H, CH3),
3.15–3.18 (m, 1H, CH), 3.95 (s, 3H, OCH3), 3.96 (s, 3H, OCH3),
7.11 (d, J ¼ 2:7 Hz, 1H, aromatic H), 7.34 (dd, J ¼ 9:2, 2.7 Hz,
1H, aromatic H), 7.60 (d, J ¼ 8:1 Hz, 2H, aromatic H), 7.99 (d,
J ¼ 9:2 Hz, 1H, aromatic H), 8.05 (s, 1H, aromatic H), 8.16 (d,
J ¼ 8:2 Hz, 2H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ
24.1 (CH3), 29.2 (CH2), 55.2, 55.5 (OCH3), 104.5, 122.0, 128.9,
129.1, 129.5, 129.6, 130.7, 131.8, 140.3, 142.3, 145.7, 156.7,
157.9 (aromatic C), 167.0 (CO); HRMS (FAB) calcd for C21H22-
NO3 ½M þ Hꢃþ 336.1600, found 336.1609; Anal. Calcd for
C21H21NO3: C, 75.20; H, 6.31; N, 4.18%. Found: C, 75.15; H,
6.41; N, 4.03%.
(Table 3, Entry 9):
(500 MHz, CDCl3) ꢁ 0.92 (d, J ¼ 6:6 Hz, 6H, CH3), 1.26 (d, J ¼
6:8 Hz, 6H, CH3), 2.19–2.25 (m, 1H, CH), 2.86 (d, J ¼ 7:3 Hz,
2H, CH2), 3.23–3.28 (m, 1H, CH), 3.90 (s, 3H, OCH3), 7.94–
7.96 (m, 2H, aromatic H), 8.12 (dd, J ¼ 9:0, 1.8 Hz, 1H, aromatic
H), 8.45 (d, J ¼ 1:8 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 22.6, 23.7 (CH3), 28.8, 29.2 (CH), 44.2 (CH2), 52.2
(OCH3), 126.4, 127.0, 127.9, 128.8, 130.4, 132.6, 141.7, 148.0,
163.4 (aromatic C), 166.9 (CO); HRMS (FAB) calcd for C18H24-
NO2 ½M þ Hꢃþ 286.1807, found 286.1801; Anal. Calcd for
C18H23NO2: C, 75.76; H, 8.12; N, 4.91%. Found: C, 75.28; H,
8.36; N, 4.67%.
General Procedure for the Synthesis of 1,2-Dialkylquino-
lines 7 in Table 4. A mixture of an aniline 1 (1.0 mmol), an ali-
phatic aldehyde 3 (2.5 mmol), and [IrCl2H(cod)]2 (0.025 mmol) in
DMSO (3 mL) was stirred at 90 ꢁC for 12 h under an air atmo-
sphere. The mixture was washed with PBS (50 mL) and extracted
with AcOEt (20 mL ꢂ 3). The organic layer was dried over
MgSO4. Removal of the solvent in vacuo, followed by chromato-
graphic purification on silica gel (AcOEt/Hexane = 5/95), af-
forded 1,2-dialkylquinoline 7.
3-Ethyl-2-propylquinoline (7a) (Table 4, Entry 1): Pale yel-
low oil (118 mg, 59%); 1H NMR (500 MHz, CDCl3) ꢁ 1.07 (t,
J ¼ 7:1 Hz, 3H, CH3), 1.33 (t, J ¼ 7:5 Hz, 3H, CH3), 1.82–1.86
(m, 2H, CH2), 2.82 (q, J ¼ 7:5 Hz, 2H, CH2), 2.94–2.97 (m,
2H, CH2), 7.42–7.45 (m, 1H, aromatic H), 7.59–7.62 (m, 1H,
aromatic H), 7.71 (d, J ¼ 8:2 Hz, 1H, aromatic H), 7.84 (s, 1H,
aromatic H), 8.01 (d, J ¼ 8:2 Hz, 1H, aromatic H); 13C NMR
(125 MHz, CDCl3) ꢁ 14.3, 14.4 (CH3), 22.8, 25.1, 37.8 (CH2),
125.5, 126.9, 127.3, 128.3, 128.5, 133.8, 135.3, 146.4, 162.0
(aromatic C); HRMS (FAB) calcd for C14H17NNa ½M þ Naꢃþ
222.1259, found 222.1282.
2-Isobutyl-3-isopropylquinoline (7d) (Table 4, Entry 13):
1
Colorless oil (225 mg, 99%); H NMR (500 MHz, CDCl3) ꢁ 1.00
(d, J ¼ 6:6 Hz, 6H, CH3), 1.33 (d, J ¼ 6:8 Hz, 6H, CH3), 2.25–
2.28 (m, 1H, CH), 2.92 (d, J ¼ 7:3 Hz, 2H, CH2), 3.31–3.34 (m,
1H, CH), 7.43–7.46 (m, 1H, aromatic H), 7.59–7.62 (m, 1H, aro-
matic H), 7.72–7.74 (m, 1H, aromatic H), 7.94 (s, 1H, aromatic
H), 8.01 (d, J ¼ 8:6 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 22.6, 23.8 (CH3), 28.8, 29.4 (CH), 44.1 (CH2), 125.5,
127.0, 127.3, 128.3, 128.5, 131.5, 140.7, 146.2, 160.8 (aromatic
C); HRMS (FAB) calcd for C16H22N ½M þ Hꢃþ 228.1752, found
228.1727; Anal. Calcd for C16H21N: C, 84.53; H, 9.31; N, 6.16%.
Found: C, 84.48; H, 9.30; N, 6.14%.
3-Isopropyl-6-methoxycarbonyl-2-phenylquinoline (6r)
1
(Table 3, Entry 9): Colorless crystals (168 mg, 55%); H NMR
(500 MHz, CDCl3) ꢁ 1.26 (d, J ¼ 6:8 Hz, 6H, CH3), 3.27–3.29
(m, 1H, CH), 4.00 (s, 3H, OCH3), 7.46–7.54 (m, 5H, aromatic
H), 8.14 (d, J ¼ 8:8 Hz, 1H, aromatic H), 8.23–8.26 (m, 2H, aro-
matic H), 8.61 (d, J ¼ 1:6 Hz, 1H, aromatic H); 13C NMR (125
MHz, CDCl3) ꢁ 24.1 (CH3), 29.3 (CH2), 52.3 (OCH3), 126.9,
127.8, 128.3, 128.3, 128.3, 128.6, 129.5, 130.4, 134.1, 140.5,
141.4, 147.9, 162.6 (aromatic C), 166.8 (CO); HRMS (FAB) calcd
for C20H20NO2 ½M þ Hꢃþ 306.1494, found 306.1461; Anal. Calcd
for C20H19NO2: C, 78.66; H, 6.27; N, 4.59%. Found: C, 78.37; H,
6.63; N, 4.31%.
2-Ethyl-6-methoxy-3-methylquinoline (7e) (Table 4, Entry
1
9): Pale yellow oil (95 mg, 47%); H NMR (500 MHz, CDCl3)
ꢁ 1.35 (t, J ¼ 7:5 Hz, 3H, CH3), 2.43 (s, 3H, CH3), 2.94 (q,
J ¼ 7:5 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 6.94 (d, J ¼ 2:8 Hz,
1H, aromatic H), 7.25 (dd, J ¼ 4:6, 2.8 Hz, 1H, aromatic H),
7.69 (s, 1H, aromatic H), 7.91 (d, J ¼ 9:0 Hz, 1H, aromatic H);
13C NMR (125 MHz, CDCl3) ꢁ 12.8, 19.0 (CH3), 29.1 (CH2),
2-Ethyl-3-methylquinoline (7c) (Table 3, Entry 2): Yellow

1948 Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006)
Facile Synthesis of Substituted Quinolines
55.3 (OCH3), 104.4, 120.6, 128.1, 129.6, 129.9, 134.7, 142.6,
157.1, 160.6 (aromatic C); HRMS (FAB) calcd for C13H16NO
½M þ Hꢃþ 202.1232, found 202.1222.
8-Ethoxycarbonyl-3-ethyl-2-propylquinoline (7l) (Table 4,
Entry 6): Yellow oil (45 mg, 17%); 1H NMR (500 MHz, CDCl3)
ꢁ 1.05 (t, J ¼ 7:5 Hz, 3H, CH3), 1.29 (t, J ¼ 7:5 Hz, 3H, CH3),
1.44 (t, J ¼ 7:2 Hz, 3H, OCH2CH3), 1.91–1.95 (m, 2H, CH2),
2.77 (q, J ¼ 7:5 Hz, 2H, CH2), 2.92 (t, J ¼ 7:5 Hz, 2H, CH2),
4.50 (q, J ¼ 7:2 Hz, 2H, OCH2CH3), 7.40 (t, J ¼ 7:6 Hz, 1H,
aromatic H), 7.76–7.78 (m, 2H, aromatic H), 7.83 (dd, J ¼ 7:2,
1.4 Hz, 1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 14.0,
14.1 (CH3), 14.3 (OCH2CH3), 21.0, 25.0, 37.1 (CH2), 61.1
(OCH2CH3), 124.4, 127.3, 128.2, 129.8, 131.7, 133.1, 136.0,
143.3, 162.3 (aromatic C), 168.9 (CO); HRMS (FAB) calcd for
C17H22NO2 ½M þ Hꢃþ 272.1651, found 272.1652.
2-Isobutyl-3-isopropyl-6-methoxyquinoline (7f) (Table 4,
Entry 11): Colorless crystals (213 mg, 83%); 1H NMR (500
MHz, CDCl3) ꢁ 0.98 (d, J ¼ 6:8 Hz, 6H, CH3), 1.32 (d, J ¼ 6:8
Hz, 6H, CH3), 2.21–2.24 (m, 1H, CH), 2.88 (d, J ¼ 7:3 Hz, 2H,
CH2), 3.28–3.32 (m, 1H, CH), 3.91 (s, 3H, OCH3), 7.03 (m, 1H,
aromatic H), 7.26–7.28 (m, 1H, aromatic H), 7.85 (s, 1H, aromatic
H), 7.90 (d, J ¼ 9:2 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 22.6, 23.9 (CH3), 28.8, 29.4 (CH), 43.9 (CH2), 55.5
(OCH3), 104.6, 120.9, 128.0, 130.0, 130.5, 141.0, 142.3, 157.1,
158.1 (aromatic C); HRMS (FAB) calcd for C17H24NO ½M þ
Hꢃþ 258.1858, found 258.1830; Anal. Calcd for C17H23NO: C,
79.33; H, 9.01; N, 5.44%. Found: C, 79.28; H, 9.09; N, 5.42%.
3-Ethyl-8-methoxy-2-propylquinoline (7h) (Table 4, Entry
3-Ethyl-6-methoxycarbonyl-2-propylquinoline (7m) (Table 4,
Entry 7): Colorless crystals (175 mg, 68%); 1H NMR (500 MHz,
CDCl3) ꢁ 1.08 (t, J ¼ 7:3 Hz, 3H, CH3), 1.36 (t, J ¼ 7:3 Hz, 3H,
CH3), 1.84–1.88 (m, 2H, CH2), 2.84–2.86 (m, 2H, CH2), 2.95–
2.99 (m, 2H, CH2), 3.98 (s, 3H, OCH3), 7.95 (s, 1H, aromatic H),
8.02–8.04 (m, 1H, aromatic H), 8.20 (dd, J ¼ 8:8, 1.8 Hz, 1H,
aromatic H), 8.51 (d, J ¼ 1:8 Hz, 1H, aromatic H); 13C NMR
(125 MHz, CDCl3) ꢁ 14.2, 14.3 (CH3), 22.6, 25.1, 37.9 (CH2),
52.2 (OCH3), 126.4, 127.0, 127.9, 128.7, 130.2, 134.8, 136.3,
148.3, 164.6 (aromatic C), 166.9 (CO); HRMS (FAB) calcd for
C16H20NO2 ½M þ Hꢃþ 258.1494, found 258.1457; Anal. Calcd
for C16H19NO2: C, 74.68; H, 7.44; N, 5.44%. Found: C, 74.60;
H, 7.51; N, 5.32%.
2):
Colorless crystals (126 mg, 55%); 1H NMR (500 MHz,
CDCl3) ꢁ 1.06 (t, J ¼ 7:3 Hz, 3H, CH3), 1.33 (t, J ¼ 7:5 Hz, 3H,
CH3), 1.82–1.84 (m, 2H, CH2), 2.84 (q, J ¼ 7:5 Hz, 2H, CH2),
2.99–3.02 (m, 2H, CH2), 4.06 (s, 3H, OCH3), 6.96 (d, J ¼ 7:5 Hz,
1H, aromatic H), 7.26–7.35 (m, 2H, aromatic H), 7.83 (s, 1H,
aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 14.4, 14.4 (CH3),
23.1, 25.1, 38.0 (CH2), 56.1 (OCH3), 106.8, 118.9, 125.5, 128.5,
133.9, 135.8, 138.3, 155.0, 161.0 (aromatic C); HRMS (FAB)
calcd for C15H20NO ½M þ Hꢃþ 230.1545, found 230.1514; Anal.
Calcd for C15H19NO: C, 78.56; H, 8.35; N, 6.11%. Found: C,
78.62; H, 8.61; N, 6.01%.
6-Methoxy-2-methylquinoline (7n) (Table 4, Entry 8): Yel-
low crystals (71 mg, 41%); 1H NMR (500 MHz, CDCl3) ꢁ 2.70
(s, 3H, CH3), 3.90 (s, 3H, OCH3), 7.03 (d, J ¼ 2:7 Hz, 1H, aro-
matic H), 7.23 (d, J ¼ 8:4 Hz, 1H, aromatic H), 7.33 (dd, J ¼
4:6, 2.7 Hz, 1H, aromatic H), 7.92 (d, J ¼ 4:6 Hz, 1H, aromatic
H), 7.93 (d, J ¼ 3:7 Hz, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 24.9 (CH3), 55.4 (OCH3), 105.2, 121.8, 122.2, 127.3,
129.9, 135.0, 143.8, 156.3, 157.2 (aromatic C); HRMS (FAB)
calcd for C11H12NO ½M þ Hꢃþ 174.0919, found 174.0907.
2-Butyl-6-methoxy-3-propylquinoline (7o) (Table 4, Entry
3-Ethyl-6-methoxy-2-propylquinoline (7i) (Table 4, Entry
1
3): Pale yellow oil (122 mg, 53%); H NMR (500 MHz, CDCl3)
ꢁ 1.06 (t, J ¼ 7:3 Hz, 3H, CH3), 1.33 (t, J ¼ 7:5 Hz, 3H, CH3),
1.79–1.84 (m, 2H, CH2), 2.80 (q, J ¼ 7:3 Hz, 2H, CH2), 2.89–
2.93 (m, 2H, CH2), 3.90 (s, 3H, OCH3), 7.00 (d, J ¼ 2:7 Hz,
1H, aromatic H), 7.26 (dd, J ¼ 4:6, 2.7 Hz, 1H, aromatic H),
7.76 (s, 1H, aromatic H), 7.90 (d, J ¼ 9:2 Hz, 1H, aromatic H);
13C NMR (125 MHz, CDCl3) ꢁ 14.3, 14.4 (CH3), 22.9, 25.2,
37.5 (CH2), 55.4 (OCH3), 104.6, 120.7, 128.1, 129.9, 132.9,
135.6, 142.5, 157.1, 159.3 (aromatic C); HRMS (FAB) calcd for
C15H20NO ½M þ Hꢃþ 230.1545, found 230.1549.
1
10): Yellow oil (126 mg, 49%); H NMR (500 MHz, CDCl3) ꢁ
0.98 (t, J ¼ 7:3 Hz, 3H, CH3), 1.04 (t, J ¼ 7:3 Hz, 3H, CH3),
1.48 (m, 2H, CH2), 1.69–1.79 (m, 4H, alkyl H), 2.73 (t, J ¼ 7:8
Hz, 2H, CH2), 2.93 (t, J ¼ 8:1 Hz, 2H, CH2), 3.89 (s, 3H, OCH3),
6.98 (d, J ¼ 2:9 Hz, 1H, aromatic H), 7.26 (dd, J ¼ 9:2, 2.7 Hz,
1H, aromatic H), 7.73 (s, 1H, aromatic H), 7.91 (d, J ¼ 9:2 Hz,
1H, aromatic H); 13C NMR (125 MHz, CDCl3) ꢁ 14.0, 14.0
(CH3), 23.0, 23.6, 31.9, 34.4, 35.3 (CH2), 55.4 (OCH3), 104.5,
120.7, 127.9, 129.8, 133.8, 134.0, 142.5, 157.0, 159.6 (aromatic
C); HRMS (FAB) calcd for C17H24NO ½M þ Hꢃþ 258.1858, found
258.1864.
3-Ethyl-8-fluoro-2-propylquinoline (7j) (Table 4, Entry 4):
Colorless oil (90 mg, 41%); 1H NMR (500 MHz, CDCl3) ꢁ 1.07
(t, J ¼ 7:5 Hz, 3H, CH3), 1.35 (t, J ¼ 7:5 Hz, 3H, CH3), 1.82–
1.87 (m, 2H, CH2), 2.85 (q, J ¼ 7:5 Hz, 2H, CH2), 2.98–3.02 (m,
2H, CH2), 7.26–7.31 (m, 1H, aromatic H), 7.34–7.38 (m, 1H, aro-
matic H), 7.51 (d, J ¼ 8:1 Hz, 1H, aromatic H), 7.89 (s, 1H, aro-
matic H); 13C NMR (125 MHz, CDCl3) ꢁ 14.2, 14.3 (CH3), 22.8,
25.2, 37.8 (CH2), 112.3 (d, JCF ¼ 19:3 Hz, aromatic C), 122.5 (d,
JCF ¼ 4:8 Hz, aromatic C), 125.2 (d, JCF ¼ 8:1 Hz, aromatic C),
129.1 (d, JCF ¼ 2:4 Hz, aromatic C), 133.4 (d, JCF ¼ 2:4 Hz, aro-
matic C), 136.5, 156.7, 158.7, 162.5 (aromatic C); HRMS (FAB)
calcd for C14H17FN ½M þ Hꢃþ 218.1345, found 218.1318.
3-Ethyl-6-fluoro-2-propylquinoline (7k) (Table 4, Entry 5):
Yellow oil (120 mg, 55%); 1H NMR (500 MHz, CDCl3) ꢁ 1.06 (t,
J ¼ 7:3 Hz, 3H, CH3), 1.34 (t, J ¼ 7:5 Hz, 3H, CH3), 1.81–1.85
(m, 2H, CH2), 2.82 (q, J ¼ 7:3 Hz, 2H, CH2), 2.92–2.95 (m,
2H, CH2), 7.32–7.38 (m, 2H, aromatic H), 7.79 (s, 1H, aromatic
H), 7.97–8.00 (m, 1H, aromatic H); 13C NMR (125 MHz, CDCl3)
ꢁ 14.2, 14.3 (CH3), 22.7, 25.1, 37.6 (CH2), 109.8 (d, JCF ¼ 21:7
Hz, aromatic C), 118.3 (d, JCF ¼ 25:8 Hz, aromatic C), 127.8
(d, JCF ¼ 9:7 Hz, aromatic C), 130.8 (d, JCF ¼ 9:7 Hz, aromatic
C), 133.1 (d, JCF ¼ 4:8 Hz, aromatic C), 136.2, 143.5, 159.0 (aro-
matic C), 161.1 (d, JCF ¼ 36:2 Hz, aromatic C); HRMS (FAB)
calcd for C14H16FNNa ½M þ Naꢃþ 240.1164, found 240.1151.
2-Isobutyl-3-isopropyl-7-methoxyquinoline (7p) (Table 4,
Entry 14): Colorless oil (93 mg, 36%); 1H NMR (500 MHz,
CDCl3) ꢁ 1.00 (d, J ¼ 6:6 Hz, 6H, CH3), 1.31 (d, J ¼ 6:8 Hz,
6H, CH3), 2.23–2.27 (m, 1H, CH), 2.90 (d, J ¼ 7:3 Hz, 2H, CH2),
3.28–3.31 (m, 1H, CH), 3.93 (s, 3H, OMe), 7.10 (d, J ¼ 8:8 Hz,
1H, aromatic H), 7.35 (s, 1H, aromatic H), 7.61 (d, J ¼ 8:8 Hz,
1H, aromatic H), 7.87 (s, 1H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 22.6, 23.9 (CH3), 28.6, 29.5 (CH), 44.0 (CH2), 55.4
(OMe), 106.5, 118.6, 122.4, 128.0, 131.3, 138.3, 147.6, 159.9,
160.7 (aromatic C); HRMS (FAB) calcd for C17H24NO ½M þ
Hꢃþ 258.1858, found 258.1852.
2-Isobutyl-3-isopropyl-5-methoxyquinoline (7p0) (Table 4,
Entry 14):
Colorless oil (10 mg, 4%); 1H NMR (500 MHz,
CDCl3) ꢁ 0.98 (d, J ¼ 6:6 Hz, 6H, CH3), 1.34 (d, J ¼ 6:8 Hz, 6H,
CH3), 2.23–2.26 (m, 1H, CH), 2.91 (d, J ¼ 7:3 Hz, 2H, CH2),
3.22–3.34 (m, 1H, CH), 4.00 (s, 3H, OMe), 6.77 (d, J ¼ 7:7 Hz,

T. Nakajima et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 12 (2006) 1949
1H, aromatic H), 7.48–7.52 (m, 1H, aromatic H), 7.60 (d, J ¼
8:6 Hz, 1H, aromatic H), 8.37 (s, 1H, aromatic H); 13C NMR
(125 MHz, CDCl3) ꢁ 22.6, 24.0 (CH3), 29.0, 29.4 (CH), 44.1
(CH2), 55.6 (OMe), 103.2, 119.6, 120.9, 126.1, 128.1, 139.9,
147.0, 154.7, 160.9 (aromatic C); HRMS (FAB) calcd for
C17H24NO ½M þ Hꢃþ 258.1858, found 258.1857.
2513. m) H. Amii, Y. Kishikawa, K. Uneyama, Org. Lett. 2001,
3, 1109. n) C. S. Cho, T. K. Kim, B. T. Kim, T.-J. Kim, S. C.
Shim, J. Organomet. Chem. 2002, 650, 65. o) J. Jacob, W. D.
Jones, J. Org. Chem. 2003, 68, 3563. p) C. S. Cho, D. T. Kim,
T.-J. Kim, S. C. Shim, Bull. Korean Chem. Soc. 2003, 24, 1026.
q) C. S. Cho, B. T. Kim, H.-J. Choi, T.-J. Kim, S. C. Shim,
Tetrahedron 2003, 59, 7997. r) A. Arcadi, M. Chiarini, S. D.
Giuseppe, F. Marinelli, Synlett 2003, 203. s) J. S. Yadav, B. V. S.
Reddy, R. S. Rao, V. Naveenkumar, K. Nagaiah, Synthesis
2003, 1610. t) C. Theeraladanon, M. Arisawa, A. Nishida, M.
Nakagawa, Tetrahedron 2004, 60, 3017. u) C. Theeraladanon,
M. Arisawa, A. Nishida, M. Nakagawa, Tetrahedron 2004, 60,
10799. v) K. Sangu, K. Fuchibe, T. Akiyama, Org. Lett. 2004,
6, 353. w) K. Motokura, T. Mizugaki, K. Ebitani, K. Kaneda,
Tetrahedron Lett. 2004, 45, 6029. x) C. S. Cho, W. X. Ren,
S. C. Shim, Bull. Korean Chem. Soc. 2005, 26, 1286. y) K.
Taguchi, S. Sakaguchi, Y. Ishii, Tetrahedron Lett. 2005, 46, 4359.
1,2-Dihydro-3-isopropyl-2-(4-methoxycarbonylphenyl)quin-
oline (11).
Yellow oil (62 mg, 20%); 1H NMR (500 MHz,
CDCl3) ꢁ 0.91 (d, J ¼ 6:8 Hz, 3H, CH3), 0.98 (t, J ¼ 6:8 Hz, 3H,
CH3), 1.94–1.97 (m, 1H, CH), 3.78 (s, 3H, OCH3), 4.08 (br, 1H,
NH), 5.06 (s, 1H, NHCH), 6.22 (d, J ¼ 7:2 Hz, 1H, aromatic H),
6.28 (s, 1H, vinyl H), 6.54 (td, J ¼ 7:3, 0.9 Hz, 1H, aromatic H),
6.81–6.86 (m, 2H, aromatic H), 7.29 (d, J ¼ 8:2 Hz, 2H, aromatic
H), 7.85 (d, J ¼ 8:2 Hz, 2H, aromatic H); 13C NMR (125 MHz,
CDCl3) ꢁ 21.0, 21.9 (CH3), 31.4 (CH2), 52.0 (OCH3), 59.2
(NHCH), 112.2 (4-C), 117.8, 119.0, 120.4, 126.4, 126.6, 128.2,
129.5, 130.1, 141.1, 142.0 (aromatic C), 148.9 (3-C); HRMS
(FAB) calcd for C20H22NO2 ½M þ Hꢃþ 308.1651, found 308.1643.
6
a) U. M. Dzhemilev, F. A. Selimov, R. A. Khusnutdinov,
Izv. Akad. Nauk SSSR, Ser. Khim. 1990, 2447. b) U. M.
Dzhemilev, F. A. Selimov, R. A. Khusnutdinov, A. A. Fatyknov,
L. M. Khalilov, G. A. Tolstikov, Izv. Akad. Nauk SSSR, Ser. Khim.
1991, 1407. c) Y. Makioka, T. Shindo, Y. Taniguchi, K. Takaki,
Y. Fujiwara, Synthesis 1995, 801. d) B. Jiang, Y.-G. Si, J. Org.
Chem. 2002, 67, 9449. e) B. C. Ranu, A. Hajra, S. S. Dey, U. Jana,
Tetrahedron 2003, 59, 813. f) B. R. McNaughton, B. L. Miller,
Org. Lett. 2003, 5, 4257. g) S. J. Song, S. J. Cho, D. K. Park,
T. W. Kwon, S. A. Jenekhe, Tetrahedron Lett. 2003, 44, 255.
h) K. Kobayashi, K. Takagoshi, S. Kondo, O. Morikawa, H.
Konishi, Bull. Chem. Soc. Jpn. 2004, 77, 553. i) T. Akiyama, S.
Nakashima, K. Yokota, K. Fuchibe, Chem. Lett. 2004, 33, 922.
j) J. S. Yadav, B. V. S. Reddy, K. Premalatha, Synlett 2004,
963. k) J. S. Yadav, B. V. S. Reddy, R. Sreedhar, S. Rao, K.
Nagaiah, Synthesis 2004, 14, 2381. l) S. K. De, R. A. Gibbs,
Tetrahedron Lett. 2005, 46, 1647. m) V. V. Kouznetsov, A. R. R.
This work was supported by a Grant-in-Aid for Initiatives
for Attractive Education for Graduate Schools (No. b043) from
the Ministry of Education, Culture, Sports, Science and Tech-
nology and Waseda University Grant for Special Research
Projects (Nos. 2004A-152 and 2005B-157). T. N. is indebted
by the Grant-in-Aid for Young Scientist (B) (No. 18750053)
from the Ministry of Education, Culture, Sports, Science and
Technology.
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