Synthesis 2013; 45(2): 205-218
DOI: 10.1055/s-0032-1316826
paper
© Georg Thieme Verlag Stuttgart · New York

Efficient [5+1] Synthesis of 4-Quinolones by Domino Amination and Conjugate Addition Reactions of 1-(2-Fluorophenyl)prop-2-yn-1-ones with Amines

Viktor O. Iaroshenko*
a   Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Fax: +49(381)49864112   Email: viktor.iaroshenko@uni-rostock.de
b   National Taras Shevchenko University, 62 Volodymyrska st., Kyiv-33, 01033, Ukraine   Email: iva108@googlemail.com
,
Satenik Mkrtchyan
a   Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Fax: +49(381)49864112   Email: viktor.iaroshenko@uni-rostock.de
,
Alexander Villinger
a   Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Fax: +49(381)49864112   Email: viktor.iaroshenko@uni-rostock.de
› Author Affiliations
Further Information

Publication History

Received: 14 September 2012

Accepted after revision: 19 November 2012

Publication Date:
07 December 2012 (online)


Abstract

A catalyst-free synthetic approach is described for the synthesis of 4-quinolone derivatives through a tandem amination/conjugated Michael addition sequence of 1-(2-fluorophenyl)prop-2-yn-1-one derivatives. The [5+1]-cyclization proceeds efficiently at a high temperature under an inert atmosphere with lithium carbonate as a base, and it provides a practical route to a diverse range of 4-quinolones. The mechanism was studied in details and several of the intermediates were isolated.

Supporting Information

 
  • References

    • 1a Silverman RB. The Organic Chemistry of Drug Design and Drug Action . 2nd ed. Elsevier Academic Press; Burlington (USA): 2004
    • 1b Analogue-Based Drug Discovery . Fischer J, Ganellin CR. Wiley-VCH; Weinheim: 2006
    • 1c Graham LP. An Introduction to Medicinal Chemistry . 4th ed. Oxford University Press; Oxford: 2009
    • 1d Collin G, Höke H In Ullmann’s Encyclopedia of Chemical Technology . Wiley-VCH; Weinheim: 2005. doi:10.1002/14356007.a22_465
    • 1e Chauhan PM. S, Srivastava SK. Curr. Med. Chem. 2001; 8: 1535
    • 1f Chen Y.-L, Fang K.-C, Sheu J.-Y, Hsu S.-L, Tzeng C.-C. J. Med. Chem. 2001; 44: 2374
    • 1g Roma G, Braccio MD, Grossi G, Mattioli F, Ghia M. Eur. J. Med. Chem. 2000; 35: 1021
    • 1h Ferraini PL, Mori C, Badawneh M, Calderone V, Greco R, Manera C, Martinelli A, Nieri P, Saccomanni G. Eur. J. Med. Chem. 2000; 35: 815
    • 1i Maguire MP, Sheets KR, McVety K, Spada AP, Zilberstein A. J. Med. Chem. 1994; 37: 2129
    • 1j Balasubramanian M, Keay JG In Comprehensive Heterocyclic Chemistry II . Vol. 5. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 245
    • 1k Antibiotics . Vol. 2. Gottlieb D, Shaw PD. Springer; Berlin: 1967: 105
    • 1l Huse H, Marvin W. Chem. Rev. 2011; 111: 152
    • 2a Alkaloids: Chemical & Biological Perspectives . Vol. 6. Pelletier SW. Wiley-VCH; Weinheim: 1988
    • 3a Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AI, Sim GA. J. Am. Chem. Soc. 1966; 88: 3888
    • 3b Adams DJ, Wahl ML, Flowers JL, Sen B, Colvin M, Dewhirst MW, Manikumar G, Wani MC. Cancer Chemother. Pharmacol. 2005; 57: 145
    • 3c Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. J. Science (Washington, D. C.) 1998; 279: 1504
    • 3d Li QY, Zu YG, Shi RZ, Yao LP. Curr. Med. Chem. 2006; 13: 2021
  • 4 Pommier Y. Chem. Rev. 2009; 109: 2894
    • 5a Trenholme GM, Williams RL, Desjardins RE, Frischer H, Carson PE, Rieckmann KH, Canfield CJ. Science (Washington, D. C.) 1975; 190: 792
    • 5b Palmer KJ, Holliday SM, Brogden RN. Drugs 1993; 45: 430
    • 5c O’Neill PM, Park BK, Shone AE, Maggs JL, Roberts P, Stocks PA, Biagini GA, Bray PG, Gibbons P, Berry N, Winstanley PA, Mukhtar A, Bonar-Law R, Hindley S, Bambal RB, Davis CB, Bates M, Hart TK, Gresham SL, Lawrence RM, Brigandi RA, Gomez-delas-Heras FM, Gargallo DV, Ward SA. J. Med. Chem. 2009; 52: 1408
    • 5d Lipkowitz MA, Navarra T. The Encyclopedia of Allergies . 2nd ed. Facts on File; New York: 2001: 178
    • 5e Corey EJ, Kürti L, Czakó B. Molecules and Medicine . Wiley; Hoboken: 2007
    • 5f Keck PE, Marcus R, Tourkodimitris S, Ali M, Liebeskind A, Saha A, Ingenito G. Am. J. Psychiatry 2003; 160: 1651
    • 5g Sachs G, Sanchez R, Marcus R, Stock E, McQuade R, Carson W, Abou-Gharbia N, Impellizzeri C, Kaplita S, Rollin L, Iwamoto T. J. Psychopharmacol. (London, U. K.) 2006; 20: 536
    • 5h Vieta E, T’joen C, McQuade RD, Carson WH, Marcus RN, Sanchez R, Owen R, Nameche L. Am. J. Psychiatry 2008; 165: 1316
    • 5i Keck PE, Orsulak PJ, Cutler AJ, Sanchez R, Torbeyns A, Marcus RN, McQuade RD, Carson WH. J. Affective Disord. 2009; 112: 36
    • 5j Keck PE, Calabrese JR, McIntyre RS, McQuade RD, Carson WH, Eudicone JM, Carlson BX, Marcus RN, Sanchez R. J. Clin. Psychiatry (Memphis, TN, U. S.) 2007; 68: 1480
    • 6a Seayad J, List B. Org. Biomol. Chem. 2005; 3: 719
    • 6b Moyano A, Rios R. Chem. Rev. 2011; 111: 4703
    • 6c Cinchona Alkaloids in Synthesis and Catalysis: Ligands, Immobilization and Organocatalysis. Song CE. Wiley-VCH; Weinheim: 2009
    • 6d Doyle AG, Jacobsen EN. Chem. Rev. 2007; 107: 5713
    • 6e Gaunt MJ, Johansson CC. C. Chem. Rev. 2007; 107: 5596
    • 9a Iaroshenko VO, Sevenard DV, Kotljarov AV, Volochnyuk DM, Tolmachev AO, Sosnovskikh VYa. Synthesis 2009; 731
    • 9b Iaroshenko VO, Wang Y, Sevenard DV, Volochnyuk DM. Synthesis 2009; 1851
    • 9c Iaroshenko VO, Wang Y, Zhang B, Volochnyuk DM, Sosnovskikh VYa. Synthesis 2009; 2393
    • 9d Iaroshenko VO. Synthesis 2009; 3967
    • 9e Mkrtchyan S, Iaroshenko VO, Dudkin S, Gevorgyan A, Vilches-Herrera M, Ghazaryan G, Volochnyuk D, Ostrovskyi D, Ahmed Z, Villinger A, Sosnovskikh VYa, Langer P. Org. Biomol. Chem. 2010; 8: 5280
    • 9f Iaroshenko VO, Mkrtchyan S, Volochnyuk DM, Langer P, Sosnovskikh VYa, Ostrovskyi D, Dudkin S, Kotljarov AV, Miliutina M, Savych I, Tolmachev AA. Synthesis 2010; 2749
    • 9g Iaroshenko VO, Ostrovskyi D, Petrosyan A, Mkrtchyan S, Villinger A, Langer P. J. Org. Chem. 2011; 76: 2899
    • 10a Craig D, Henry GD. Tetrahedron Lett. 2005; 46: 2559
    • 10b Kelly TR, Lebedev RL. J. Org. Chem. 2002; 67: 2197
    • 10c Zhang Q, Sun S, Hu J, Liu Q, Tan J. J. Org. Chem. 2007; 72: 139
    • 10d Huang Q, Hunter JA, Larock RC. Org. Lett. 2001; 3: 2973
    • 10e Harschneck T, Kirsch SF. J. Org. Chem. 2011; 76: 2145
    • 10f Zhang H, Larock RC. J. Org. Chem. 2002; 67: 7048
    • 10g Zhao T, Xu B. Org. Lett. 2010; 212
    • 10h Huang Q, Hunter JA, Larock RC. J. Org. Chem. 2002; 67: 3437
    • 10i Meketa ML, Weinreb SM. Org. Lett. 2006; 8: 1443
    • 10j Zeni G, Larock RC. Chem. Rev. 2004; 104: 2285
    • 10k Zeni G, Larock RC. Chem. Rev. 2006; 106: 4644
    • 10l Berninia R, Cacchi S, Fabrizib G, Sferrazza A. Synthesis 2009; 1209
    • 10m Friary RJ, Seidl V, Schwerdt JH, Chan T.-M, Cohen MP, Conklin ER, Duelfer T, Hou D, Nafissi M, Runkle RL, Tahbaz P, Tiberi RL, McPhail AT. Tetrahedron 1993; 49: 7179
    • 10n Iaroshenko VO, Knepper I, Zahid M, Dudkin S, Kuzora R, Villinger A, Langer P. Org. Biomol. Chem. 2012; 10: 2955
    • 10o Shao J, Huang X, Hong X, Liu B, Xu B. Synthesis 2012; 44: 1798
    • 10p Fokin AS, Burgart YaV, Saloutin VI, Chupakhin ON. J. Fluor. Chem. 2001; 108: 187
    • 10q Fokin AS, Burgart YaV, Saloutin VI, Chupakhin ON. Russ. J. Org. Chem. (Engl. Transl.) 2005; 41: 1354
    • 11a Iaroshenko VO, Groth U, Kryvokhyzha NV, Obeid S, Tolmachev AA, Wesch T. Synlett 2008; 343
    • 11b Jepsen TH, Larsen M, Jørgensen M, Nielsen MB. Synlett 2012; 23: 418
    • 11c Awasaguchi K, Hayashi H, Kawai H, Tominaga H, Sato Y, Hayashi K, Todo Y. Synlett 2012; 23: 448
    • 11d Cherepakha A, Kovtunenko VO, Tolmachev A, Lukin O. Tetrahedron 2011; 67: 6233
    • 12a Norman MH, Navas F, Thompson JB, Rigdon GC. J. Med. Chem. 1996; 39: 4692
    • 12b Pessoa-Mahana H, Kosche CJ, Ron HN, Recabarren-Gajardo G, Saitz BC, Araya-Maturana R, Pessoa-Mahana CD. Heterocycles 2008; 75: 1913
    • 12c Holt J, Tjosås F, Bakke J, Fiksdahl A. J. Heterocycl. Chem. 2004; 41: 987
    • 12d Tjosås F, Fiksdahl A. Molecules 2006; 11: 130
    • 12e El-Kaïm L, Grimaud L, Purumandla SR. Synlett 2012; 23: 295
  • 13 Crystallographic data (excluding structure factors) for compounds 5g, 5q, 6b, 8b, and 11a have been deposited with the accession numbers 868711, 868712, 868715, 868716, and 907162, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.