Ruthenium-catalyzed oxidative coupling and cyclization between 2-aminobenzyl alcohol and secondary alcohols leading to quinolines

Article abstract of DOI:10.1016/j.tet.2003.08.027

2-Aminobenzyl alcohol is oxidatively coupled and cyclized with secondary alcohols in dioxane at 80°C in the presence of a catalytic amount of RuCl₂(PPh₃)₃ and KOH along with 1-dodecene as a sacrificial hydrogen acceptor to give the corresponding quinolines in good yields. The cyclization is applicable to a wide range of alkyl(aryl) and alkyl(alkyl) carbinols. The catalytic pathway seems to be proceeded via a sequence involving initial oxidation of both substrates to carbonyl compounds, cross aldol reaction, and cyclodehydration.

Full text of DOI:10.1016/j.tet.2003.08.027

Tetrahedron 59 (2003) 7997–8002
Ruthenium-catalyzed oxidative coupling and cyclization
between 2-aminobenzyl alcohol and secondary alcohols
leading to quinolines
a,*
b
Chan Sik Cho, Bok Tae Kim, Heung-Jin Choi, Tae-Jeong Kim and Sang Chul Shim
b
b
b,*
a
Research Institute of Industrial Technology, Kyungpook National University, Taegu 702-701, South Korea
Department of Industrial Chemistry, Kyungpook National University, Taegu 702-701, South Korea
b
Received 14 July 2003; accepted 6 August 2003
Abstract—2-Aminobenzyl alcohol is oxidatively coupled and cyclized with secondary alcohols in dioxane at 808C in the presence of a
catalytic amount of RuCl (PPh ) and KOH along with 1-dodecene as a sacrificial hydrogen acceptor to give the corresponding quinolines in
2
3 3
good yields. The cyclization is applicable to a wide range of alkyl(aryl) and alkyl(alkyl) carbinols. The catalytic pathway seems to be
proceeded via a sequence involving initial oxidation of both substrates to carbonyl compounds, cross aldol reaction, and cyclodehydration.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
It is known that many quinoline containing compounds
exhibit a wide spectrum of pharmacological activities such
1
as antiasthmatic, antiinflammatory and antimalarial. Thus,
besides conventional named routes such as Skraup, D o¨ bner-
von Miller, Conrad-Limpach, Friedlaender and Pfitzinger
2
syntheses, homogeneous transition metal-catalyzed syn-
thetic methods have also been developed as alternative
methods for the construction of quinoline framework
because of efficiency of reaction and wide availability of
Scheme 1.
3
substrates. During the course of our ongoing studies on
homogeneous ruthenium-catalysis for the synthesis of
between secondary alcohols and primary alcohols which
eventually leads to b-alkylation of the former by the latter
4
,5
N-heterocycles, we have also reported on ruthenium-
catalyzed synthesis of quinolines via an alkyl group transfer
12
(
Scheme 1, route c). These findings led us to attempt the
cyclization of 2-aminobenzyl alcohol with secondary
alcohols leading to quinolines since compounds possessing
secondary alcohol moiety can be directly subjected to react
with 2-aminobenzyl alcohol for quinoline framework with-
out preoxidation of the secondary alcohol to ketone. Herein,
we report a successful ruthenium-catalyzed oxidative
coupling and subsequent cyclization between 2-amino-
benzyl alcohol and secondary alcohols in the presence of
KOH and 1-dodecene leading to quinolines.
3
b,5
from a-hydrogen containing alkyl amines to anilines
6
(
amine exchange reaction ) and an oxidative cyclization of
7
2
-aminobenzyl alcohol with ketones (modified Fried-
8
laender quinoline synthesis ). The latter was intrinsically
based on our recent report, an unusual type of ruthenium-
catalyzed transfer hydrogenation between ketones and
primary alcohols accompanied by carbon–carbon coupling
under KOH, in which alkylated ketones (Scheme 1, route a)
or unconventional transfer hydrogenated secondary alcohols
9
1
0
(Scheme 1, route b) were preferentially formed according
1
to the molar ratio of primary alcohols to ketones.
1
2
. Results and discussion
Furthermore, in connection with this report, we recently
disclosed an unprecedented ruthenium-catalyzed coupling
Based on our recent report on ruthenium-catalyzed
oxidative cyclization of 2-aminobenzyl alcohol (1) with
Keywords: 2-aminobenzyl alcohol; cyclization; oxidative coupling;
quinolines; ruthenium catalyst; secondary alcohols.
7
ketones and oxidative coupling between secondary
1
2
*
Corresponding authors. Tel.: þ82-53-950-7318; fax: þ82-53-950-6594;
alcohols and primary alcohols, several tentative results
for the reaction between 1 and 1-phenylethanol (2a) are
e-mail: cscho@knu.ac.kr
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.027

7998
C. S. Cho et al. / Tetrahedron 59 (2003) 7997–8002
summarized in Table 1. When 1 was allowed to react with
equimolar amount of 2a in the presence of RuCl2-
Table 2. Ruthenium-catalyzed synthesis of quinolines 3 from 1 and 2
(
(
(
except as noted, all reactions were carried out with 1 (1 mmol), 2
1 mmol), RuCl (PPh (0.02 mmol), KOH (1 mmol), and l-dodecene
5 mmol) in dioxane (2 mL) at 808C for 20 h)
2
3 3
)
(
vCHPh)(PCy ) (1 mol%) along with KOH, 2-phenyl-
3 2
quinoline (3a) was produced in only 10% yield (Table 1, run
). However, the addition of 1-dodecene as hydrogen
acceptor increased the yield of 3a to 52% (run 2). It appears
a
1
Secondary alcohols 2
Quinolines 3
Yield (%)
that the reaction is similarly accelerated by the addition of
1-dodecene as we have observed that secondary alcohols
and primary alcohols are easily coupled in the presence of
1
2,13
1
-dodecene.
Table 1, the yield of 3a increased gradually from 1% (1 h),
9% (5 h), 29% (10 h), 42% (15 h), to 52% (20 h).
RuCl (PPh ) could be alternatively used as catalyst, 3a
Under the catalytic system of run 2 in
R¼Ph (2a)
R¼Ph (3a)
74
87
85
71
85
82
48
73
57
90
R¼4-MeC
R¼3-MeC
R¼2-MeC
6
6
6
H
H
H
4
4
4
(2b)
(2c)
(2d)
R¼4-MeC
R¼3-MeC
R¼2-MeC
6
6
6
H
H
H
4
4
4
(3b)
(3c)
(3d)
1
2
3 3
R¼4-MeOC H (2e)
R¼4-MeOC H (3e)
6
4
6
4
being formed in 53% yield (run 3). By increasing the
amount of ruthenium catalyst to 2 mol%, a higher yield
(74%) of 3a was achieved (run 4). However, performing the
reaction under more amount of KOH did not give any
R¼4-FC H (2f)
R¼4-FC H (3f)
6
4
6 4
R¼4-pyridyl (2g)
R¼2-thienyl (2h)
R¼2-furanyl (2i)
R¼2-naphthyl (2j)
R¼4-pyridyl (3g)
R¼2-thienyl (3h)
R¼2-furanyl (3i)
R¼2-naphthyl (3j)
1
4
significant change (run 5). Treatment of equimolar
amount of 1 and 2a is desirable in atom economy point of
view since the reaction under the molar ratio of [2a]/[1]¼1.5
6
1
1
5
results in a slightly increased yield of 3a (run 6).
Having established reaction conditions, various secondary
alcohols 2 were subjected to react with 1 in order to
investigate the reaction scope and several representative
results are summarized in Table 2. With aryl(methyl)
carbinols (2a–2f) the oxidative coupling and cyclization
products were formed in the range of 71–87% yields with
the minimal formation of acetophenones on GLC analysis.
The product yield was not significantly affected by the
position and electronic nature of the substituent on the
aromatic ring of 2a–2f. The reaction proceeds likewise with
heteroaryl(methyl) carbinols (2g–2i) to give the corre-
sponding 2-heteroaryl substituted quinolines (3g–3i) and
the quinoline yield was lower than that when aryl(methyl)
carbinols were used. 1-(2-Naphthyl)ethanol (2j) was also
readily oxidatively coupled and cyclized with 1 to afford
b
R¼Me (2l)
R¼Me (3l)
56
42
R¼i-Pr (2m)
R¼i-Pr (3m)
c
R¼phenethyl (2n)
R¼pentyl (2o)
R¼phenethyl (3n)
R¼pentyl (3o)
60
d
43
4
3
5
4
9
6
2
-(2-naphthyl)quinoline (3j) in 90% yield. The reaction of
-phenyl-1-propanol (2k), which has only methylene
1
reaction site, with 1 also proceeds to give the corresponding
quinoline 3k in 61% yield. From the reactions between 1
and alkyl(alkyl) carbinols (2l–2p), the corresponding
quinolines (3l–3p) were also produced in moderate to
good yields. In the case of isopropanol (2l), the molar ratio
of [2l]/[1]¼3 was necessary for the effective formation of 3l.
a
Isolated yield.
3 mmol of isopropanol was used.
b
c
3-Benzyl-2-methylquinoline was also formed in 16% yield.
3
d
-Butyl-2-methylquinoline was also formed in 10% yield.
Table 1. Optimization of conditions for the reaction of 1 with 2a (except as
noted, all reactions were carried out with 1 (1 mmol), 2a (1 mmol), KOH
In the reaction of unsymmetrical alkyl(alkyl) carbinols 2n
and 2o which have methyl and methylene reaction sites, the
corresponding quinolines 3n and 3o were obtained as a
regioisomeric mixture, favoring oxidative coupling and
cyclization at less-hindered methyl position over methylene
position. Similar observations have also been made by our
recent reports on ruthenium-catalyzed a-alkylation of
(1 mmol), and 1-dodecene (5 mmol) in dioxane (2 mL) at 808C for 20 h)
a
Run
Ruthenium catalysts (mol%)
Hydrogen acceptor
Yield (%)
1
6
9
ketones with trialkylamines and primary alcohols and
1
2
1
2
3
4
RuCl
RuCl
RuCl
RuCl
RuCl
RuCl
2
2
2
2
2
2
(vCHPh)(PCy
(vCHPh)(PCy
3
)
)
2
2
(1)
(1)
–
10
52
53
74
74
78
b-alkylation of secondary alcohols with primary alcohols.
It is also known that palladium-catalyzed a-arylation of
3
1-dodecene
1-dedecene
1-dodecene
1-dodecene
1-dodecene
(PPh
(PPh
(PPh
(PPh
3
3
3
3
)
)
)
)
3
3
3
3
(1)
(2)
(2)
(2)
ketones with aryl halides regioselectively occurs at less-
17
hindered methyl position over a-methylene and -methine.
Cyclic carbinols such as cyclopentanol (2q) and 1-tetralol
(2r) were also reacted with 1 to give 2,3-dihydro-1H-
cyclopenta[b]quinoline (3q) and 5,6-dihydrobenzo[c]acri-
dine (3r), respectively.
b
5
c
6
a
Isolated yield.
KOH (2 mmol).
b
c
[
2a]/[1]¼1.5.

C. S. Cho et al. / Tetrahedron 59 (2003) 7997–8002
7999
Scheme 2.
As to the reaction pathway, it seems to proceed via a
sequence involving initial oxidations of both substrates to
carbonyl compounds 4 and 5, cross aldol reaction under
KOH to afford a,b-unsaturated ketone 6, and cyclo-
dehydration (Scheme 2). The initial oxidations of alcohols
to carbonyl compounds, which proceed via oxidative
addition of ruthenium to O–H bond and subsequent
b-hydrogen elimination, are well documented in transition
3.1. Typical procedure for ruthenium-catalyzed
oxidative coupling and cyclization between 2-amino-
benzyl alcohol and secondary alcohols
A mixture of 2-aminobenzyl alcohol (0.123 g, 1 mmol),
1-phenylethanol (0.122 g, 1 mmol), RuCl (PPh ) (0.019 g,
2
3 3
0.02 mmol), 1-dodecene (0.842 g, 5 mmol) and KOH
(0.056 g, 1 mmol) in dioxane (2 mL) was placed in a
5 mL screw-capped vial. The system was allowed to react at
808C for 20 h. The reaction mixture was filtered through a
short silica gel column (ethyl acetate) to eliminate inorganic
salts. Removal of the solvent left a crude mixture, which
was separated by thin layer chromatography (silica gel,
ethyl acetate–hexane mixture) to give quinoline (0.151 g,
74%).
1
1
metal-catalyzed transfer hydrogenations. As has been
1
2
observed in our recent report, 1-dodecene seems to act as a
sacrificial hydrogen acceptor oxidizing [Ru]H generated in
2
the initial oxidation stage to [Ru]. An alternative route for 3
involves a sequence such as reduction of 6 to saturated
ketone 7, cyclodehyderation to form 3,4-dihydroquinoline 8
1
8
and dehydrogenation.
In summary, we have demonstrated that 2-aminobenzyl
alcohol can be oxidatively coupled and cyclized with an
array of secondary alcohols under the conditions of
RuCl (PPh ) /KOH/1-dodecene/dioxane/808C to afford
quinolines in moderate to good yields. The present reaction
will be useful for the direct quinoline formation from
3.1.1. 2-Phenylquinoline (3a). Solid (hexane); mp 84–
2
0
1
858C (lit. 83–848C); H NMR (400 MHz, CDCl ) d 7.41–
3
7.52 (m, 4H), 7.67–7.71 (m, 1H), 7.76 (d, J¼8.0 Hz, 1H),
1
3
7.80 (d, J¼8.5 Hz, 1H), 8.12–8.18 (m, 4H); C NMR
2
3 3
(100 MHz, CDCl ) d 118.9, 126.2, 127.1, 127.4, 127.5,
3
128.7, 129.2, 129.5, 129.6, 136.7, 139.6, 148.2, 157.2; MS
þ
2-aminobenzyl alcohol and secondary alcohols without
preoxidation of the secondary alcohols to ketones.
m/z (relative intensity) 205 (M , 100).
3.1.2. 2-(4-Methylphenyl)quinoline (3b). Solid (hexane);
mp 80–818C (lit. 81–828C); H NMR (400 MHz, CDCl )
2
1
1
3
3
. Experimental
d 2.41 (s, 3H), 7.31 (d, J¼8.0 Hz, 2H), 7.46–7.50 (m, 1H),
7
.67–7.71 (m, 1H), 7.76–7.82 (m, 2H), 8.05 (d, J¼8.0 Hz,
) d
3
1
13
13
H and C NMR (400 and 100 MHz) spectra were recorded
2H), 8.15 (t, J¼8.0 Hz, 2H); C NMR (100 MHz, CDCl
on a Bruker Avance Digital 400 spectrometer using TMS as
an internal standard. Melting points were determined on a
Thomas–Hoover capillary melting point apparatus and
were uncorrected. Mass spectra were obtained on a
Shimadzu QP-1000 spectrometer. GLC analyses were
carried out with Shimadzu GC-17A (FID) equipped with
CBP10-S25-050 column (Shimadzu, a silica fused capillary
21.3, 118.8, 126.0, 127.0, 127.4, 129.5, 129.6, 136.6, 136.8,
þ
139.3, 148.2, 157.2; MS m/z (relative intensity) 219 (M ,
100).
2
2
1
3.1.3. 2-(3-Methylphenyl)quinoline (3c). Viscous oil; H
NMR (400 MHz, CDCl
) d 2.43 (s, 3H), 7.23 (d, J¼7.5 Hz,
3
1H), 7.37 (t, J¼7.5 Hz, 1H), 7.42–7.46 (m, 1H), 7.65–7.77
column, 0.33 mm£25 m, 0.25 mm film thickness) using N
(m, 3H), 7.89 (d, J¼7.5 Hz, 1H), 7.98 (s, 1H), 8.07 (d,
2
1
3
as carrier gas. The isolation of pure products was carried out
via column (silica gel 60, 70–230 mesh, Merck) and thin
layer (silica gel 60 GF254, Merck) chromatography.
Secondary alcohols 2b–2j were prepared by reduction of
the corresponding ketones with LiAlH . RuCl (PPh ) was
J¼8.5 Hz, 1H), 8.17 (d, J¼8.5 Hz, 1H);
(100 MHz, CDCl ) d 21.5, 118.9, 124.6, 126.0, 127.0,
3
C NMR
127.3, 128.1, 128.6, 129.4, 129.5, 130.0, 136.5, 138.3,
þ
139.5, 148.1, 157.4; MS m/z (relative intensity) 219 (M ,
100).
4
2
3 3
1
9
prepared by the reported method. Commercially available
organic and inorganic compounds were used without further
purification.
2
3
1
3.1.4. 2-(2-Methylphenyl)quinoline (3d). Viscous oil; H
NMR (400 MHz, CDCl ) d 2.40 (s, 3H), 7.21–7.32 (m, 3H),
3

8000
C. S. Cho et al. / Tetrahedron 59 (2003) 7997–8002
2
9
1
7
.41–7.54 (m, 3H), 7.71 (t, J¼7.5 Hz, 1H), 7.81 (d,
3.1.12. 2-Methylquinoline (3l). Pale yellow oil; H NMR
(400 MHz, CDCl ) d 2.73 (s, 3H), 7.25 (d, J¼8.5 Hz, 1H),
1
3
J¼8.5 Hz, 1H), 8.15–8.18 (m, 2H); C NMR (100 MHz,
3
CDCl ) d 20.2, 122.3, 125.9, 126.3, 126.6, 127.4, 128.4,
3
7.46 (t, J¼7.5 Hz, 1H), 7.66 (t, J¼7.8 Hz, 1H), 7.74 (d,
C NMR
1
3
1
1
29.4, 129.5, 129.6, 130.8, 135.9, 136.0, 140.6, 147.7,
þ
J¼8.0 Hz, 1H), 8.01 (t, J¼7.3 Hz, 2H);
(100 MHz, CDCl ) d 25.3, 121.9, 125.6, 126.4, 127.4,
3
60.1; MS m/z (relative intensity) 219 (M , 30), 218 (100).
128.5, 129.3, 136.1, 147.8, 158.9.
3
mp 117–1188C (lit. 122–1238C); H NMR (400 MHz,
.1.5. 2-(4-Methoxyphenyl)quinoline (3e). Solid (hexane);
2
3
1
30
1
3.1.13. 2-Isopropylquinoline (3m). Pale yellow oil; H
NMR (400 MHz, CDCl ) d 1.39 (d, J¼7.0 Hz, 6H), 3.26
CDCl ) d 3.82 (s, 3H), 7.01 (d, J¼9.0 Hz, 2H), 7.45 (t,
3
3
J¼7.5 Hz, 1H), 7.67 (t, J¼7.5 Hz, 1H), 7.74 (t, J¼7.8 Hz,
(hept, J¼7.0 Hz, 1H), 7.32 (d, J¼8.5 Hz, 1H), 7.46 (t,
J¼7.5 Hz, 1H), 7.66 (t, J¼7.3 Hz, 1H), 7.75 (d, J¼8.0 Hz,
1
3
2
5
1
H), 8.07–8.14 (m, 4H); C NMR (100 MHz, CDCl ) d
3
1
3
5.2, 114.1, 118.4, 125.8, 127.3, 128.8, 129.4, 129.5, 130.4,
32.1, 136.5, 148.2, 156.7, 160.7.
1H), 8.06 (d, J¼8.6 Hz, 2H); C NMR (100 MHz, CDCl )
3
d 22.5, 37.3, 119.1, 125.6, 126.9, 127.4, 128.9, 129.2, 136.3,
147.7, 167.6.
2
4
3
mp 92–938C; H NMR (400 MHz, CDCl ) d 7.13–7.17 (m,
.1.6. 2-(4-Fluorophenyl)quinoline (3f). Solid (hexane);
1
29
1
3.1.14. 2-Phenethylquinoline (3n). Pale yellow oil; H
NMR (400 MHz, CDCl ) d 3.12–3.16 (m, 2H), 3.25–3.29
(m, 2H), 7.14–7.18 (m, 2H), 7.21–7.27 (m, 4H), 7.43 (t,
3
2
4
1
1
H), 7.44–7.48 (m, 1H), 7.65–7.73 (m, 3H), 8.06–8.14 (m,
1
3
3
H); C NMR (100 MHz, CDCl ) d 115.6 (d, J¼21.3 Hz),
3
18.4, 126.2, 126.9, 127.4, 129.3 (d, J¼7.8 Hz), 129.5,
J¼7.5 Hz, 1H), 7.65 (t, J¼7.5 Hz, 1H), 7.71 (d, J¼8.0 Hz,
1
3
29.6, 135.6 (d, J¼2.9 Hz), 135.7, 148.1, 156.0, 163.7 (d,
1H), 7.95 (d, J¼8.5 Hz, 1H), 8.08 (d, J¼8.5 Hz, 1H);
NMR (100 MHz, CDCl ) d 35.7, 40.8, 121.4, 125.6, 125.8,
3
C
þ
J¼247.3 Hz); MS m/z (relative intensity) 223 (M , 100).
126.6, 127.4, 128.2, 128.4, 128.7, 129.2, 136.0, 141.3,
147.8, 161.6.
2
5
3
9
1
.1.7. 2-(4-Pyridyl)quinoline (3g). Solid (hexane); mp
1
1–928C; H NMR (400 MHz, CDCl ) d 7.56–7.60 (m,
3
H), 7.74–7.79 (m, 1H), 7.85 (d, J¼8.0 Hz, 1H), 7.89 (d,
3.1.15. 3-Benzyl-2-methylquinoline. This regioisomer was
isolated as a mixture with the starting 4-phenyl-2-butanol,
and the yield was calculated from the peak areas of
the clearly separated protons in H NMR spectrum; H
NMR (400 MHz, CDCl ) d 2.64 (s, 3H, CH ), 4.13 (s, 2H,
CH2).
J¼8.5 Hz, 1H), 8.08 (d, J¼5.0 Hz, 2H), 8.19 (d, J¼8.5 Hz,
1
3
1
(
H), 8.27 (d, J¼8.5 Hz, 1H), 8.79 (s, 2H); C NMR
1
1
100 MHz, CDCl ) d 118.3, 121.6, 127.2, 127.5, 127.8,
3
1
29.9, 130.1, 137.2, 146.7, 148.2, 150.1, 154.2.
3
3
3
1
7
4
1
1
.1.8. 2-(2-Thienyl)quinoline (3h). Solid (hexane); mp
1
2
6
31
1
268C (lit. 125–1278C); H NMR (400 MHz, CDCl ) d
3
3.1.16. 2-Pentylquinoline (3o). Pale yellow oil; H NMR
(400 MHz, CDCl ) d 0.90 (t, J¼6.8 Hz, 3H), 1.29–1.44 (m,
.14 (t, J¼4.5 Hz, 1H), 7.44–7.48 (m, 2H), 7.66–7.77 (m,
3
1
3
H), 8.07–8.10 (m, 2H); C NMR (100 MHz, CDCl ) d
3
4H), 1.77–1.85 (m, 2H), 2.96 (t, J¼8.0 Hz, 2H), 7.27 (d,
J¼8.5 Hz, 1H), 7.43–7.47 (m, 1H), 7.64–7.68 (m, 1H),
17.6, 125.8, 126.0, 127.1, 127.4, 128.0, 128.5, 129.2,
29.8, 136.6, 145.3, 148.0, 152.3; MS m/z (relative
1
3
7.74 (d, J¼8.5 Hz, 1H), 8.04 (t, J¼9.3 Hz, 2H); C NMR
þ
intensity) 211 (M , 100).
(100 MHz, CDCl ) d 13.9, 22.5, 29.7, 31.7, 39.3, 121.3,
3
1
25.5, 126.6, 127.4, 128.7, 129.2, 136.1, 147.8, 163.0.
7
3
8
1
.1.9. 2-(2-Furanyl)quinoline (3i). Solid (hexane); mp
1
31
1
8–908C; H NMR (400 MHz, CDCl ) d 6.48–6.54 (m,
3
3.1.17. 3-Butyl-2-methylquinoline. Pale yellow oil; H
NMR (400 MHz, CDCl ) d 0.98 (t, J¼7.3 Hz, 3H), 1.41–
H), 7.13–7.18 (m, 1H), 7.42 (t, J¼7.5 Hz, 1H), 7.53–7.74
3
(
1
m, 4H), 8.04 (d, J¼8.6 Hz, 1H), 8.12 (d, J¼8.0 Hz, 1H);
1.50 (m, 2H), 1.63–1.70 (m, 2H), 2.72 (s, 3H), 2.75 (t,
J¼7.5 Hz, 2H), 7.44 (t, J¼7.3 Hz, 1H), 7.58–7.63 (m, 1H),
13
3
C NMR (100 MHz, CDCl ) d 109.9, 112.0, 117.2, 126.0,
3
1
1
26.9, 127.4, 129.1, 129.6, 136.4, 143.9, 147.9, 148.8,
þ
7.71 (d, J¼8.0 Hz, 1H), 7.82 (s, 1H), 7.99 (d, J¼8.5 Hz,
53.5; MS m/z (relative intensity) 195 (M , 100).
1H); C NMR (100 MHz, CDCl ) d 13.9, 22.6, 23.1, 31.8,
3
32.5, 125.6, 126.8, 127.3, 128.2, 128.4, 134.3, 134.4, 146.3,
158.6.
3
1
7
1
2
.1.10. 2-(2-Naphthyl)quinoline (3j). Solid (hexane); mp
7
2
1
62–1638C (lit. 1638C); H NMR (400 MHz, CDCl ) d
3
3
2
.49–7.53 (m, 3H), 7.70–7.75 (m, 1H), 7.79 (d, J¼8.0 Hz,
3.1.18. 3-Butyl-2-pentylquinoline (3p). Pale yellow oil;
1
H), 7.86–7.88 (m, 1H), 7.96–7.98 (m, 3H), 8.18–8.23 (m,
H), 8.35 (dd, J¼8.6, 2.0 Hz, 1H), 8.59 (s, 1H); C NMR
H NMR (400 MHz, CDCl ) d 0.92 (t, J¼7.0 Hz, 3H), 0.98
3
1
3
(t, J¼7.5 Hz, 3H), 1.37–1.50 (m, 6H), 1.63–1.70 (m, 2H),
1.77–1.84 (m, 2H), 2.77 (t, J¼7.8 Hz, 2H), 2.97 (t,
J¼8.0 Hz, 2H), 7.40–7.43 (m, 1H), 7.57–7.61 (m, 1H),
(
100 MHz, CDCl ) d 119.1, 125.0, 126.3, 126.7, 127.1,
3
1
1
27.2, 127.5, 127.7, 128.5, 128.8, 129.7, 133.4, 133.8,
36.7, 136.9, 148.3, 157.1; MS m/z (relative intensity) 255
7.69 (d, J¼8.0 Hz, 1H), 7.82 (s, 1H), 8.02 (d, J¼8.6 Hz,
þ
13
(
M , 100).
1H); C NMR (100 MHz, CDCl ) d 13.9, 14.0, 22.5, 22.6,
3
29.4, 32.0, 32.1, 32.6, 35.8, 125.4, 126.8, 127.2, 128.2,
128.4, 134.0, 134.7, 146.5, 162.2.
2
8
3
oil; H NMR (400 MHz, CDCl ) d 2.41 (s, 3H), 7.38–7.48
.1.11. 3-Methyl-2-phenylquinoline (3k). Pale yellow
1
3
3
3
(
m, 4H), 7.55–7.58 (m, 2H), 7.60–7.64 (m, 1H), 7.71 (d,
1
3.1.19. 2,3-Dihydro-1H-cyclopenta[b]quinoline (3q).
1
3
J¼8.0 Hz, 1H), 7.93 (s, 1H), 8.13 (d, J¼8.5 Hz, 1H);
C
NMR (100 MHz, CDCl ) d 20.5, 126.2, 126.5, 127.4, 128.0,
Pale yellow oil; H NMR (400 MHz, CDCl ) d 2.16–2.24
3
(m, 2H), 3.08 (t, J¼7.4 Hz, 2H), 3.16 (t, J¼7.6 Hz, 2H),
13
3
1
1
28.1, 128.6, 128.7, 129.0, 129.1, 136.6, 140.7, 146.4,
þ
7.43–7.47 (m, 1H), 7.59–7.63 (m, 1H), 7.72 (d, J¼8.2 Hz,
60.3; MS m/z (relative intensity) 219 (M , 50), 218 (100).
1H), 7.87 (s, 1H), 8.01 (d, J¼8.4 Hz, 1H); C NMR

C. S. Cho et al. / Tetrahedron 59 (2003) 7997–8002
8001
(
1
100 MHz, CDCl ) d 23.6, 30.5, 34.6, 125.5, 127.3, 127.4,
3
28.3, 128.5, 130.3, 135.6, 147.5, 167.9.
regioselective Friedlaender quinoline synthesis, see: Hsiao,
Y.; Rivera, N. R.; Yasuda, N.; Hughes, D. L.; Reider, P. J. Org.
Lett. 2001, 3, 1101.
3
mp 63–658C (lit. 658C); H NMR (400 MHz, CDCl ) d
.1.20. 5,6-Dihydrobenzo[c]acridine (3r). Solid (hexane);
3
9. Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. Tetrahedron
Lett. 2002, 43, 7987.
4
1
3
2
7
7
1
2
1
.93–2.97 (m, 2H), 3.02–3.06 (m, 2H), 7.20–7.24 (m, 1H),
.31–7.35 (m, 1H), 7.38–7.44 (m, 2H), 7.59–7.63 (m, 1H),
.67 (d, J¼8.0 Hz, 1H), 7.83 (s, 1H), 8.12 (d, J¼8.0 Hz,
10. Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. J. Org. Chem.
2001, 66, 9020.
11. For recent reviews on transition metal-catalyzed transfer
hydrogenation, see: Zassinovich, G.; Mestroni, G.; Gladiali, S.
Chem. Rev. 1992, 92, 1051; B a¨ ckvall, J.-E.; Chowdhury, R. L.;
Karlsson, U.; Wang, G. In Perspectives in Coordination
Chemistry; Williams, A. F., Floriani, C., Merbach, A. E., Eds.;
VCH: New York, 1992; pp 463–486; Noyori, R.; Hashiguchi,
S. Acc. Chem. Res 1997, 30, 97; Naota, T.; Takaya, H.;
Murahashi, S.-I. Chem. Rev. 1998, 98, 2599; Palmer, M.;
Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045.
1
3
H), 8.56–8.58 (m, 1H); C NMR (100 MHz, CDCl ) d
3
8.3, 28.7, 125.9, 126.8, 127.2, 127.8, 127.9, 128.5, 129.3,
29.6, 130.5, 133.6, 134.6, 139.3, 147.5, 153.3; MS m/z
þ
(
relative intensity) 231 (M , 100).
Acknowledgements
1
2. Cho, C. S.; Kim, B. T.; Kim, H.-S.; Kim, T.-J.; Shim, S. C.
Organometallics 2003, 22, 3608.
C. S. C. gratefully acknowledges a MOE-KRF Research
Professor Program (KRF-2001-050-D00015).
1
3. In Ref. [12], the reaction rate toward coupling between
secondary alcohols and primary alcohols (Scheme 1, route c)
was dramatically enhanced by the addition of 1-dodecene.
This seemed to be considered as a facile regeneration of [Ru]
References
from [Ru]H
reducing 1-dodecene to dodecane (see Scheme 2).
2
generated in the initial oxidation stages by
1
. Arcadi, A.; Chiarini, M.; Giuseppe, S. D.; Marinelli, F. Synlett
003, 203, and references cited therein.
2
14. It is also known that strong bases are used as cocatalysts to
promote transition metal-catalyzed transfer hydrogenation.
However, in the present reaction, KOH seems to act as a base
for aldol reaction as well as a promotor for transfer
hydrogenation.
2
. Jones, G. Comprehensive Heterocyclic Chemistry; Katritzky,
A. R., Rees, C. W., Eds.; Pergamon: New York, 1984; Vol. 2,
p 395.
3
. (a) Amii, H.; Kishikawa, Y.; Uneyama, K. Org. Lett. 2001, 3,
1
109, and references cited therein. (b) Cho, C. S.; Oh, B. H.;
Kim, J. S.; Kim, T.-J.; Shim, S. C. Chem. Commun. 2000,
885, and references cited therein.
15. In contrast to this result, the molar ratio [ketones]/[1] in
oxidative cyclization of 1 with ketones (Ref. 7) was critical for
the effective formation of quinolines since superfluous ketones
are partially consumed by transfer hydrogenation of ketones
by 1.
1
4
. For the synthesis of indoles: Cho, C. S.; Lim, H. K.; Shim,
S. C.; Kim, T. J.; Choi, H.-J. Chem. Commun. 1998, 995; Cho,
C. S.; Kim, J. H.; Shim, S. C. Tetrahedron Lett. 2000, 41,
16. Cho, C. S.; Kim, B. T.; Lee, M. J.; Kim, T.-J.; Shim, S. C.
Angew. Chem., Int. Ed. 2001, 40, 958.
1
811; Cho, C. S.; Kim, J. H.; Kim, T.-J.; Shim, S. C.
Tetrahedron 2001, 57, 3321; Cho, C. S.; Kim, J. H.; Choi,
H.-J.; Kim, T.-J.; Shim, S. C. Tetrahedron Lett. 2003, 44,
17. Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
11108; Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997,
119, 12382.
2
. Cho, C. S.; Oh, B. H.; Shim, S. C. Tetrahedron Lett. 1999, 40,
975.
5
18. Tsuji, Y.; Nishimura, H.; Huh, K.-T.; Watanabe, Y.
J. Organomet. Chem. 1985, 286, C44; Larock, R. C.; Kuo,
M. Tetrahedron Lett. 1991, 32, 569.
1
499; Cho, C. S.; Oh, B. H.; Shim, S. C. J. Heterocycl. Chem.
999, 36, 1175; Cho, C. S.; Kim, J. S.; Oh, B. H.; Kim, T.-J.;
1
Shim, S. C. Tetrahedron 2000, 56, 7747; Cho, C. S.; Kim,
T. K.; Kim, B. T.; Kim, T.-J.; Shim, S. C. J. Organomet. Chem.
19. Hallman, P. S.; Stephenson, T. A.; Wilkinson, G. Inorg. Synth.
1970, 12, 237.
2002, 650, 65; Cho, C. S.; Kim, T. K.; Choi, H.-J.; Kim, T.-J.;
Shim, S. C. Bull. Korean Chem. Soc. 2002, 23, 541.
20. Wiebe, J. M.; Caill e´ , A. S.; Trimble, L.; Lau, C. K.
Tetrahedron 1996, 52, 11705.
6
. For transition metal-catalyzed amine exchange reaction, see:
Yoshimura, N.; Moritani, I.; Shimamura, T.; Murahashi, S.-I.
J. Am. Chem. Soc. 1973, 95, 3038; Murahashi, S.-I.; Hirano,
T.; Yano, T. J. Am. Chem. Soc. 1978, 100, 348; Shvo, Y.;
Laine, R. M. J. Chem. Soc., Chem. Commun. 1980, 753; Khai,
B.-T.; Concilio, C.; Porzi, G. J. Organomet. Chem. 1981, 208,
21. Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 801.
22. Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett 1999, 401.
23. Mahanty, J. S.; De, M.; Das, P.; Kundu, N. G. Tetrahedron
1997, 53, 13397.
24. Cenini, S.; Bettettini, E.; Fedele, M.; Tollari, S. J. Mol. Catal.
A: Chem. 1996, 111, 37.
2
49; Khai, B.-T.; Concilio, C.; Porzi, G. J. Org. Chem. 1981,
6, 1759; Arcelli, A.; Khai, B.-T.; Porzi, G. J. Organomet.
25. Furukawa, N.; Shibutani, T.; Fujihara, H. Tetrahedron Lett.
1987, 28, 5845.
4
Chem. 1982, 231, C31; Murahashi, S.-I.; Kondo, K.; Hakata,
T. Tetrahedron Lett. 1982, 23, 229; Laine, R. M.; Thomas,
D. W.; Cary, L. W. J. Am. Chem. Soc. 1982, 104, 1763; Jung,
C. W.; Fellmann, J. D.; Garrou, P. E. Organometallics 1983, 2,
26. F u¨ rstner, A.; Leitner, A.; M e´ ndez, M.; Krause, H. J. Am.
Chem. Soc. 2002, 124, 13856.
27. Brown, B. R.; Hammick, D. L.; Newbould, J.; Price, A. L.
J. Chem. Soc. 1959, 1311.
1
042; Murahashi, S.-I. Angew. Chem. Int. Ed. 1995, 34, 2443.
28. Ciufolini, M. A.; Mitchell, J. W.; Roschangar, F. Tetrahedron
Lett. 1996, 37, 8281.
7
. Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. Chem.
Commun. 2001, 2576.
29. Avramoff, M.; Sprinzak, Y. J. Am. Chem. Soc. 1956, 78, 4090.
30. Fakhfakh, M. A.; Franck, X.; Fournet, A.; Hocquemiller, R.;
Figad e` re, B. Tetrahedron Lett. 2001, 42, 3847.
8
. Friedlaender, P. Chem. Ber. 1882, 15, 2572. For a review, see:
Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37. For a

8002
C. S. Cho et al. / Tetrahedron 59 (2003) 7997–8002
3
1. Sch o¨ pf, C.; Lehmann, G. Justus Liebigs Ann. Chem. 1932,
97, 7.
33. Curran, D. P.; Liu, H. J. Am. Chem. Soc. 1991, 113, 2127.
34. Bell, V. L.; Cromwell, N. H. J. Org. Chem. 1958, 23, 789.
4
3
2. Dzhemilev, U. M.; Selimov, F. A.; Khusnutdinov, R. A. Akad.
Nauk S. S. S. R. 1990, 2447.