Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of 4-quinolones
Recent Literature
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.
β-Amido ynones can be efficiently and chemoselectively transformed to
3-acyl-substituted quinolones and 3-H-quinolones depending on the use of
anhydrous or wet ethylene glycol.
W.-S. Chen, F. Yang, T. Wang, G.-Q. Zhang, Y. Wei, M.-H. Wang, Z.-S. Chen, K.
Ji, Org. Lett., 2023, 25,
5762-5767.
The use of transition-metal catalysts and TEMPO enables an efficient
synthesis of 2-phenyl-4H-chromen-4-one, 2-phenylquinolin-4(1H)-one,
and 11H-benzofuro[3,2-b]chromen-11-one derivatives in good yields
from 2'-hydroxychalcones, 2'-aminochalcones, and 3-hydroxyflavones, respectively.
The methods offer high atom-economy, use of benign solvent and auxiliaries, and
easy handling.
A. Singh, S. Singh, K. Ghosh, N. Ahmed, Synthesis, 2023,
55, 4191-4203.
A Cu-catalyzed tandem C-N and C-C bond-formation reaction of aryl boronic acid (or
pinacolate ester) with nitriles provides 2-substituted-4-(1H)-quinolones.
This environmentally friendly one-step method uses a cheap Cu-catalyst and O2
(air) as a green oxidant.
S. Tummanapalli, K. C. Gulipalli, S. Bodige, A. K. Pommidi, R. Boya, S. Choppadandi, M. R. Bakangari, S. K. Punna, S. Medaboina, D. Y. Mamindla, A. Kanuka, S. Endoori, V. K. Ganapathi, S. Dharmavaram k., D. Kalbhor, M. Valluri, J. Org. Chem., 2024, 89,
1609-1617.
Potassium halides serve as both halogenating agents and electrolytes for an
effective C3-H halogenation of quinoline-4(1H)-ones under electrochemical
conditions. The protocol provides expedient access to different halogenated
quinoline-4(1H)-ones with unique regioselectivity, broad substrate scope,
and gram-scale synthesis in an undivided cell.
M. Hu, S. Zhang, C. Qin, H. Nie, Z. Xiong, X. Shi, Y. Zhao, M. Li, S. Wang, F.
Ji, G. Jiang, J. Org. Chem., 2023, 88,
12952-12970.
An iron(III)-catalyzed oxidative coupling of alcohols/methyl arenes with
2-amino phenyl ketones provides a broad range of 4-quinolones. Alcohols and methyl arenes are
oxidized to the aldehyde in the presence of an iron catalyst and di-tert-butyl
peroxide, followed by condensation with amine/Mannich-type
cyclization/oxidation.
S. B. Lee, Y. Jang, J. Ahn, S. Chun, D.-C. Oh, S. Hong,
Org. Lett., 2020, 22, 8382-8386.
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.
3-Hydroxyquinoline-4(1H)-ones (3HQs) are privileged structural motifs.
Phosphine mediates a redox transformation of easily accessible
1-(2-nitroaryl)prop-2-ynones to 3HQs under neutral conditions. The synthetic
utility of this formal intramolecular oxyamination of α,β-ynones is demonstrated
in the total synthesis of japonine, its analogs, and rare quinoline derivatives.
L. Dutta, S. S. V. Ramasastry, Org. Lett.,
2022, 24, 7665-7670.