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Volumn 72, Issue 21, 2007, Pages 7968-7973

Sequential Cu-catalyzed amidation-base-mediated camps cyclization: A two-step synthesis of 2-aryl-4-quinolones from o-halophenones

Author keywords

[No Author keywords available]

Indexed keywords

AMINES; CATALYST ACTIVITY; COPPER COMPOUNDS; CYCLIZATION; LIGANDS; SYNTHESIS (CHEMICAL);

EID: 35348846488     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo701384n     Document Type: Article
Times cited : (176)

References (70)
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    • It is known that 4-quinolones have two tautomeric forms and can be drawn as either the 4-hydroxyquinolines in the enol-form or as 4-quinolones in the keto-form (Scheme 1). Both forms are important in understanding the characterization data and the chemical reactivity of such compounds. However, it is believed that in the solid state, as well as in many solvents, these compounds exist primarily in the keto-form. Therefore, for the purposes of this publication, we will refer to and draw the products as 4-quinolones. For discussions on the tautomerization of hydroxyquinolines see: (a) Reitsema, R. H. Chem. Rev. 1948, 43, 43-68.
    • It is known that 4-quinolones have two tautomeric forms and can be drawn as either the 4-hydroxyquinolines in the enol-form or as 4-quinolones in the keto-form (Scheme 1). Both forms are important in understanding the characterization data and the chemical reactivity of such compounds. However, it is believed that in the solid state, as well as in many solvents, these compounds exist primarily in the keto-form. Therefore, for the purposes of this publication, we will refer to and draw the products as 4-quinolones. For discussions on the tautomerization of hydroxyquinolines see: (a) Reitsema, R. H. Chem. Rev. 1948, 43, 43-68.
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    • Selected references on 2-aryl-4-quinolones as antitumor agents: (a) Kuo, S.-C.; Lee, H.-Z.; Juang, J.-P.; Lin, Y.-T.; Wu, T.-S.; Chang, J.- J.; Lednicer, D.; Pauli, K. D.; Lin, C. M.; Hamel, E.; Lee, K.-H. J. Med. Chem. 1993, 36, 1146-1156.
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    • For methods utilizing Eaton's reagent: (d) Dorow, R. L.; Herrinton, P. M.; Hohler, R. A.; Maloney, M. T.; Mauragis, M. A.; McGhee, W. E.; Moeslein, J. A.; Strohbach, J. W.; Veley, M. F. Org. Process Res. Dev. 2006, 10, 493-499.
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    • Niementowski methods: (f) Niementowski, S. Ber. Dtsch. Chem. Ges. 1894, 27, 1394-1403.
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    • (a) Camps, R. Chem. Ber. 1899, 32, 3228-3234.
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    • References indicating catalyst-free amination reactions: (a) Beller, M.; Breindl, C.; Riermeier, T. H.; Tillack, A. J. Org. Chem. 2001, 66, 1403-1412.
    • References indicating catalyst-free amination reactions: (a) Beller, M.; Breindl, C.; Riermeier, T. H.; Tillack, A. J. Org. Chem. 2001, 66, 1403-1412.
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    • Aryl iodides were found to be better starting materials for the more difficult Cu-catalyzed amidation reactions of 2-halophenones with alkyl amides, which are not discussed in this publication due to their problematic reactivity in the Camps cyclization
    • Aryl iodides were found to be better starting materials for the more difficult Cu-catalyzed amidation reactions of 2-halophenones with alkyl amides, which are not discussed in this publication due to their problematic reactivity in the Camps cyclization.
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    • 4 for the facilitation of Cu-catalyzed amidation with aryl iodides reported in our earlier work (ref 20b).
    • 4 for the facilitation of Cu-catalyzed amidation with aryl iodides reported in our earlier work (ref 20b).
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    • For example, N-(2-acetylphenyl)-n-hexanamide (32) cyclized to afford 25% of 4-methyl-3-n-butyl-2-quinolone (33) and 49% of 2-n-pentyl-4-quinolone (34).
    • For example, N-(2-acetylphenyl)-n-hexanamide (32) cyclized to afford 25% of 4-methyl-3-n-butyl-2-quinolone (33) and 49% of 2-n-pentyl-4-quinolone (34).


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