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presence of a catalytic amount of a ruthenium catalyst (1 mol%
based on 1) and KOH to afford 2-phenylquinoline (3). The
reaction was monitored until 1 had disappeared on TLC, which
occurred within 1 h. The product yield increased with increase
in reaction temperature up to 80 °C (runs 1–3). Tuning the molar
ratio of 2 to 1 was critical for the effective formation of 3. Upon
using equimolar amounts of 1 and 2, the yield of 3 was lower
than that when the molar ratio of 2 was used (run 4). This could
be due to partial consumption of 2 leading to 1-phenylethanol
by transfer hydrogenation of 2 by 1. Of various ruthenium
yields. The present reaction is a novel transition metal-catalysed
Friedlaender quinoline synthesis.
The present work was supported by the Basic Research
Program of the Korea Science and Engineering Foundation
(R01-2000-00044). C.S.C. gratefully acknowledges a MOE-
KRF Research Professor Program (2001-050-D00015).
Notes and references
†
General experimental procedure: a mixture of 2-aminobenzyl alcohol (1
mmol), ketone (2 mmol), RuCl (NCHPh)(PCy (0.01 mmol) and KOH (1
2
3 2
)
2 3 2
catalysts employed, RuCl (NCHPh)(PCy ) is the choice of
mmol) in dioxane (3 ml) was placed in a 5 ml screw-capped vial. The system
was flushed with argon and allowed to react at 80 °C for 1 h. The reaction
mixture was filtered through a short silica gel column (ethyl acetate),
washed with brine and dried over Na SO . Removal of the solvent left a
preference for the effective formation of 3 (runs 5–11). In all
cases, 3 was formed in moderate to high yields with concomi-
tant formation of 1-phenylethanol by transfer hydrogenation of
2
4
2
by 1 ranging from 5–12%.† 9
Given suitable reaction conditions, a series of ketones were
crude mixture, which was separated by column chromatography (silica gel,
ethyl acetate–hexane mixture) to give quinolines.
screened in order to scrutinise the reaction scope, and several
representative results are summarised in Table 2. Alkyl aryl
ketones were readily cyclised with 1 irrespective of the
examined functional groups on the aromatic ring to afford the
corresponding 2-arylquinolines in excellent to good yields. The
quinoline yield was not greatly affected by the position of the
substituent on the aromatic ring of ketones, whereas the
electronic nature of that had some relevance to the product
yield. Lower reaction rate and yield were observed with
acetophenones having nitro, hydroxy and cyano functional
groups on the aromatic ring. With alkyl heteroaryl ketones, the
corresponding quinolines were also formed in high yields. In the
reaction of dialkylketones, the corresponding quinolines were
obtained as a regioisomeric mixture, favoring cyclisation at
1
J. Jones, Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky
and C. W. Rees, Pergamon, New York, 1984, vol. 2, pp. 395–510.
H. Amii, Y. Kishikawa and K. Uneyama, Org. Lett., 2001, 3, 1109.
For the formation of quinolines catalysed by transition metals such as
Pd, Rh, Ru and Fe, see: ref. 4d.
(a) C. S. Cho, B. H. Oh and S. C. Shim, Tetrahedron Lett., 1999, 40,
1499; (b) C. S. Cho, B. H. Oh and S. C. Shim, J. Heterocycl. Chem.,
1999, 36, 1175; (c) C. S. Cho, J. S. Kim, B. H. Oh, T.-J. Kim and S. C.
Shim, Tetrahedron, 2000, 56, 7747; (d) C. S. Cho, B. H. Oh, J. S. Kim,
T.-J. Kim and S. C. Shim, Chem. Commun., 2000, 1885.
C. S. Cho, H. K. Lim, S. C. Shim, T. J. Kim and S. C. Shim, Chem.
Commun., 1998, 995; C. S. Cho, J. H. Kim and S. C. Shim, Tetrahedron
Lett., 2000, 41, 1811; C. S. Cho, J. H. Kim, T.-J. Kim and S. C. Shim,
Tetrahedron, 2001, 57, 3321; C. S. Cho, T. K. Kim, S. W. Yoon, T.-J.
Kim and S. C. Shim, Bull. Korean Chem. Soc., 2001, 22, 545.
C. S. Cho, B. T. Kim, M. J. Lee, T.-J. Kim and S. C. Shim, Angew.
Chem., Int. Ed., 2001, 40, 958.
2
3
4
5
6
6,7,10
less-hindered position over a-methylene.
An array of alkyl
aryl, cyclic and benzo-fused cyclic ketones having only the
methylene reaction site also afforded the corresponding prod-
ucts ranging from 66–97%.
7 C. S. Cho, B. T. Kim, T.-J. Kim and S. C. Shim, J. Org. Chem., in
press.
8
9
P. Friedlaender, Chem. Ber., 1882, 15, 2572;; For a review, see: C.-C.
Cheng and S.-J. Yan, Org. Reactions, 1982, 28, 37.
For recent reviews, see: R. Noyori and S. Hashiguchi, Acc. Chem. Res.,
As to the reaction pathway, this seems to proceed via an
initial oxidative addition of ruthenium to O–H bond of 1
followed by b-hydrogen elimination to give 2-aminobenzalde-
hyde. The precedents of such an oxidative addition have been
well documented in several transfer hydrogenation reactions.9
In summary, we have demonstrated that 2-aminobenzyl
alcohol can be oxidatively cyclised with an array of ketones in
the presence of a ruthenium catalyst to give quinolines in high
1997, 30, 97; T. Naota, H. Takaya and S.-I. Murahashi, Chem. Rev.,
1998, 98, 2599; M. Palmer and M. Wills, Tetrahedron: Asymmetry,
1999, 10, 2045.
1
0 Exclusive regioselective Friedlaender quinoline synthesis using b-keto
phosphonates has recently been reported: Y. Hsiao, N. R. Rivera, N.
Yasuda, D. L. Hughes and P. J. Reider, Org. Lett., 2001, 3, 1101.
Chem. Commun., 2001, 2576–2577
2577