A Novel and Facile Method for the Synthesis of 2,3-Disubstituted Quinolines by a Three-Component Coupling Reaction

Satoshi Kikuchi; Masahiro Iwai; Shin-ichi Fukuzawa

doi:10.1055/s-2007-991058

LETTER

A Novel and Facile Method for the Synthesis of 2,3-Disubstituted Quinolines by a Three-Component Coupling Reaction

Satoshi Kikuchi, Masahiro Iwai, Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
Fax: +81(3)38171895; e-Mail: fukuzawa@chem.chuo-u.ac.jp;

Abstract

All articles of this category

Abstract

A Lewis acid effectively catalyzed the three-component coupling reaction of an aromatic amine and aldehyde with ethyl propiolate, and the 2,3-disubstituted quinoline was regioselectively obtained in a good yield (up to 83% GC yield).

Key words

Lewis acid - quinolines - three-component coupling reaction - regioselectively

Full Text

References

References and Notes

<A NAME="RU06707ST-1">1</A> Balalaie S. Kowsari E. Monatsh. Chem. 2001, 132: 1551

<A NAME="RU06707ST-2A">2a</A> Balasubramanian M. Keay JG. In Comprehensive Heterocyclic Chemistry II Vol. 5: Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford / New York: 1996. p.245

<A NAME="RU06707ST-2B">2b</A> Michael JP. Nat. Prod. Rep. 1997, 14: 605

<A NAME="RU06707ST-3A">3a</A> Aggarwal AK. Jenekhe SA. Macromolecules 1991, 24: 6806

<A NAME="RU06707ST-3B">3b</A> Zhang X. Shetty AS. Jenekhe SA. Macromolecules 1999, 32: 7422

<A NAME="RU06707ST-3C">3c</A> Jenekhe SA. Lu L. Alam MM. Macromolecules 2001, 34: 7315

<A NAME="RU06707ST-3D">3d</A> Aoki S. Sakurama K. Matsuo N. Yamada Y. Takasawa R. Tanuma S. Shiro M. Takeda K. Kimura E. Chem. Eur. J. 2006, 12: 9066

<A NAME="RU06707ST-3E">3e</A> Qu S. Lin Z. Duan C. Zhang H. Bai Z. Chem. Commun. 2006, 4392

<A NAME="RU06707ST-3F">3f</A> Shavaleev NM. Adams H. Best J. Edge R. Navaratnam S. Weinstein JA. Inorg. Chem. 2006, 45: 9410

For recent reports on the synthesis of quinoline derivatives, see:

<A NAME="RU06707ST-4A">4a</A> Duvelleroy D. Perrio C. Parisel O. Lasne M.-C. Org. Biomol. Chem. 2005, 3: 3794

<A NAME="RU06707ST-4B">4b</A> Kouznetsov VV. Méndez LYV. Gómez CMM. Curr. Org. Chem. 2005, 9: 141

<A NAME="RU06707ST-4C">4c</A> Familoni OB. Klaas PJ. Lobb KA. Pakade VE. Kaye PT. Org. Biomol. Chem. 2006, 4: 3960

<A NAME="RU06707ST-4D">4d</A> Wu J. Xia H. Gao K. Org. Biomol. Chem. 2006, 4: 126

<A NAME="RU06707ST-4E">4e</A> Tanaka S. Yasuda M. Baba A. J. Org. Chem. 2006, 71: 800

<A NAME="RU06707ST-4F">4f</A> Wu Y. Liu L. Li H. Wang D. Chen Y. J. Org. Chem. 2006, 71: 6592

<A NAME="RU06707ST-4G">4g</A> Korivi RP. Cheng C. J. Org. Chem. 2006, 71: 7079

<A NAME="RU06707ST-4H">4h</A> Sakai N. Annaka K. Konakahara T. J. Org. Chem. 2006, 71: 3653

<A NAME="RU06707ST-4I">4i</A> Asao N. Iso K. Yudha SS. Org. Lett. 2006, 8: 4149

<A NAME="RU06707ST-4J">4j</A> Sromek AW. Rheingold AL. Wink DJ. Gevorgyan V. Synlett 2006, 2325

<A NAME="RU06707ST-4K">4k</A> Abbiati G. Arcadi A. Marinelli F. Rossi E. Verdecchia M. Synlett 2006, 3218

<A NAME="RU06707ST-4L">4l</A> Muscia GC. Bollini M. Carnevale JP. Bruno AM. Asis SE. Tetrahedron Lett. 2006, 47: 8811

<A NAME="RU06707ST-4M">4m</A> Cho CS. Ren WX. Shim SC. Tetrahedron Lett. 2006, 47: 6781

<A NAME="RU06707ST-4N">4n</A> Lin X.-F. Cui S.-L. Wang Y.-G. Tetrahedron Lett. 2006, 47: 3127

<A NAME="RU06707ST-4O">4o</A> Wang G.-W. Jia C.-S. Dong Y.-W. Tetrahedron Lett. 2006, 47: 1059

<A NAME="RU06707ST-4P">4p</A> Li A. Ahmed E. Chen X. Cox M. Crew AP. Dong H. Jin M. Ma L. Panicker B. Siu KW. Steinig AG. Stolz KM. Tavares PAR. Volk B. Weng Q. Werner D. Mulvihill MJ. Org. Biomol. Chem. 2007, 5: 61

<A NAME="RU06707ST-4Q">4q</A> Arcadi A. Bianchi G. Inesi A. Marinelli F. Rossi L. Synlett 2007, 103

There are a few reports for the synthesis of 2-aryl-3-carboalkoxy quinoline using Friedländer reaction. For examples, see:

<A NAME="RU06707ST-5A">5a</A> Patteux C. Levacher V. Dupas G. Org. Lett. 2003, 5: 3061

<A NAME="RU06707ST-5B">5b</A> Leleu S. Papamicaël C. Marsais F. Dupas G. Levacher V. Tetrahedron: Asymmetry 2004, 15: 3919

When this reaction was carried out at reflux in toluene, the major product was the 1,4-dihydropyridines. The investiga-tion regarding the synthesis of 1,4-dihydropyridines will be reported elsewhere in due course.

<A NAME="RU06707ST-7">7</A> We performed this reaction using TfOH (10 mol%) at reflux in EtOH, and obtained the quinoline 4aa in 50% yield.

General Procedure: To the EtOH (5 mL) solution of 1a (53.9 mg, 0.5 mmol), 2a (55 µL, 0.54 mmol) and Lewis acid (0.05 mmol, 10 mol%) was added 3 (61 µL, 0.6 mmol) using a microsyringe and then the mixture was refluxed for 24 h. The reaction was quenched with sat. aq NaHCO₃ and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO₄. The organic layer was filtered and concentrated under reduced pressure. The yield of 4aa was determined by GC using biphenyl as the internal standard. The quinoline 4aa was purified by preparative TLC (SiO₂; hexane-EtOAc, 7:1) and/or recycling preparative HPLC (GPC column, CHCl₃ as an eluent) and was fully characterized.
Ethyl 6-Methyl-2-phenylquinoline-3-carboxylate (4aa): ¹H NMR (300 MHz, CDCl₃): δ = 1.06 (t, J = 6.9 Hz, 3 H), 2.55 (s, 3 H), 4.17 (q, J = 6.9 Hz, 2 H), 7.44 (m, 3 H), 7.62 (m, 4 H), 8.07 (d, J = 9.0 Hz, 1 H), 8.55 (s, 1 H). ¹³C NMR (CDCl₃): δ = 13.6, 21.5, 61.4, 125.4, 125.8, 126.8, 128.1, 128.3, 128.4, 129.1, 133.8, 137.2, 138.3, 140.8, 146.9, 157.2, 168.1.

The reaction with imine 5, which was prepared from 1a and 2a, using Sc(OTf)₃ yielded the quinoline 4aa in 60% yield.

CCDC 650434 contains the supplementary crystallographic data for compound 4ha. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.

Typical Procedure (Scheme 2): To the EtOH (7 mL) solution of 1a (107.2 mg, 1.0 mmol), 2d (110 µL, 1.1 mmol), which was distilled from P₂O₅ before use, and Sc(OTf)₃ (49.2 mg, 0.10 mmol) was added 3 (122 µL, 1.2 mmol) using a microsyringe and then the mixture was refluxed for 24 h. The reaction was quenched with sat. aq NaHCO₃ and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO₄. This organic layer was filtered and concentrated under reduced pressure. The residue was purified by short column chromatography (hexane-EtOAc, 6:1) and recycling preparative HPLC (GPC column, CHCl₃ as an eluent) to give the pure 4ad in 34% yield.
Diethyl 6-Methylquinoline-2,3-dicarboxylate (4ad): ¹H NMR (300 MHz, CDCl₃): δ = 1.45 (m, 6 H), 2.57 (s, 3 H), 4.43 (q, J = 7.0 Hz, 2 H), 4.52 (q, J = 7.0 Hz, 2 H), 7.67 (m, 2 H), 8.09 (d, J = 5.8 Hz, 1 H), 8.67 (s, 1 H). ¹³C NMR (CDCl₃): δ = 14.1, 21.6, 61.4, 62.2, 122.5, 127.1, 127.3, 129.4, 134.6, 138.7, 138.9, 146.6, 147.0, 165.3, 166.9.

<A NAME="RU06707ST-12">12</A> The CuOTf-catalyzed 1,4-addition of EtOH to ethyl propiolate has been reported. See: Bertz SH. Dabbagh G. Cotte P. J. Org. Chem. 1982, 47: 2216

<A NAME="RU06707ST-13A">13a</A> Makioka Y. Shindo T. Taniguchi Y. Takaki K. Fujiwara Y. Synthesis 1995, 801

<A NAME="RU06707ST-13B">13b</A> Kobayashi S. Ishitani H. Nagayama S. Synthesis 1995, 1195

In this reaction, ethyl 3,3-diethoxypropionate was obtained predominantly.