Synthesis of 4-quinolones
A Co(III)-catalyzed enaminone-directed C-H coupling with dioxazolones and subsequent deacylation of an installed amide group provides quinolones, an important heterocyclic scaffold for diverse pharmaceutically active structures.
P. Shi, L. Wang, K. Chen, J. Wang, J. Zhu, Org. Lett., 2017, 19, 2418-2421.
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.
An efficient Cu(I)-catalyzed direct cyclization of readily available primary anilines and alkynes provides diverse 4-quinolones. Thiophenols and phenols are also viable substrates for this reaction. Moreover, secondary arylamines can be converted to dihydroepindolidiones.
X. Xu, R. Sun, S. Zhang, X. Zhang, W. Yi, Org. Lett., 2018, 20, 1893-1897.
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.
A Cu-catalyzed formation of 4-quinolones from simple and readily available anilines and alkynes offers mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. Under optimized conditions, both N-alkyl- and N-aryl-substituted anilines can be successfully transformed into the corresponding 4-quinolones.
X. Xu, X. Zhang, Org. Lett., 2017, 19, 4984-4987.
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.
4-Quinolones and 4H-thiochromen-4-ones are readily synthesized in a tandem one-pot manner from (Z)-β-chlorovinyl ketones in in good to excellent yields. An intermolecular nucleophilic addition of amines or sodium hydrogen sulfide to (Z)-β-chlorovinyl ketones is followed by elimination of a chlorine anion to give a Z-enamine or thioenol intermediate, which gives the desired products through intramolecular SNAr reaction.
D. Wang, P. Sun, P. Jia, J. Peng, Y. Yue, C. Chen, Synthesis, 2017, 49, 4309-4320.
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.
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.
An efficient transition-metal-free oxidative cyclization reaction of alkynes with isatins enables a facile synthesis of structurally diverse 4-quinolones.
S.-F. Jiang, C. Xu, Z.-W. Zhou, Q. Zhang, X.-H. Wen, F.-C. Jia, A.-X. Wu, Org. Lett., 2018, 20, 4231-4234.
A highly efficient Cu-catalyzed aza-Michael addition of 2-aminobenzoates to β-substituted α,β-unsaturated ketones followed by cyclization and a mild oxidation reaction enable a straightforward one-pot synthesis of 3-carbonyl-4-quinolone derivatives in very good yields under mild reaction conditions with short reaction times.
S. Kang, S. Park, K.-s. Kim, C. Song, Y. Lee, J. Org. Chem., 2018, 83, 2694-2705.
A base-promoted insertion of ynones into the C-N σ-bond of amides enables a transition-metal-free synthesis of substituted quinolin-4(1H)-ones or enaminones. Easily accessible starting materials and high atom economy make this procedure attractive.
Z. Zheng, Q. Tao, Y. Ao, M. Xu, Y. Li, Org. Lett., 2018, 20, 3907-3910.