Categories: Synthesis of N-Heterocycles >
Synthesis of 4-quinolones
The use of arylhydrazines as aryl radical source and air as oxidant enables a transition-metal-free C-3-arylation of quinolin-4-ones in the presence of a base. The reaction proceeds smoothly at room temperature without either prefunctionalization or N-protection of quinoline-4-ones.
M. Ravi, P. Chauhan, R. Kant, S. K. Shukla, P. P. Yadav, J. Org. Chem., 2015, 80, 5369-5376.
Using TEMPO as the oxidant and KOtBu as the base enables a metal-free, a simple and direct access to a broad range of 2-arylquinolin-4(1H)-ones from readily available N-arylmethyl-2-aminophenylketones via oxidative intramolecular Mannich reaction.
W. Hu, J.-P. Lin, L.-R. Song, Y.-Q. Long, Org. Lett., 2015, 17, 1268-1271.
N-Alkyl-substituted 4-quinolones are present as the key structural motif in many marketed drugs. An efficient and convenient one-step tandem amination approach affords N-alkyl-substituted 4-quinolones in high yields from easily accessible o-chloroaryl acetylenic ketones and functionalized alkyl amines.
J. Shao, X. Huang, X. Hong, B. Liu, B. Xu, Synthesis, 2012, 44, 1798-1808.
An efficient palladium-catalyzed tandem amination approach affords functionalized 4-quinolones in very good yields from easily accessible o-haloaryl acetylenic ketones and primary amines.
T. Zhao, B. Xu, Org. Lett., 2010, 12, 212-215.
Intermolecular Michael addition of an amine to a (Z)-β-chlorovinyl ketone followed by elimination of a chloride anion provides enamine intermediates, with full retention of the initial Z-configuration. These intermediates can be transformed into quinolin-4(1H)-one products by a palladium-catalyzed intramolecular N-arylation in a tandem one-pot manner, with good to excellent yields.
Y. Wang, H. Liang, C. Chen, D. Wang, J. Peng, Synthesis, 2015, 47, 1851-1860.
Two different protocols for a palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence enable the preparation of functionalized 4-quinolones from 2-iodoanilines and alkynes in the presence of molybdenum hexacarbonyl as a solid source of CO. The first method yields the cyclized products after only 20 min of microwave heating at 120°C. The second method is a one-pot two-step sequence which runs at room temperature.
L. Åkerbladh, P. Nordeman, M. Wdjdemar, L. R. Odell, M. Larhed, J. Org. Chem., 2015, 80, 1464-1471.
A mild ICl-induced cyclization of heteroatom-substituted alkynones provides a simple, highly efficient approach to various 3-iodochromones, iodothiochromenones, iodoquinolinones and analogues in good to excellent yields. Subsequent palladium-catalyzed transformations afford a rapid increase in molecular complexity.
C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org. Chem., 2006, 71, 1626-1632.
1,2-Disubstituted 4-quinolones have been prepared via copper-catalyzed heterocyclization of 1-(2-bromophenyl)- and 1-(2-chlorophenyl)-2-en-3-amin-1-ones, readily obtained from α,β-ynones and primary amines. The reaction tolerates a variety of useful functionalities including ester, keto, cyano, and chloro substituents. Quinolone derivatives can also be directly prepared from α,β-ynones.
R. Bernini, S. Cacchi, G. Fabrizi, A. Sferrazza, Synthesis, 2009, 1209-1219.