Recent Advances in One-Pot Modular Synthesis of 2-Quinolones

Abstract

It is known that 2-quinolones are broadly applicable chemical structures in medicinal and agrochemical research as well as various functional materials. A number of current publications about their synthesis and their applications emphasize the importance of these small molecules. The early synthetic chemistry originated from the same principle of the classical Friedländer and Knorr procedures for the preparation of quinolines. The analogous processes were developed by applying new synthetic tools such as novel catalysts, the microwave irradiation method, etc., whereas recent innovations in new bond forming reactions have allowed for novel strategies to construct the core structures of 2-quinolones beyond the bond disconnections based on two classical reactions. Over the last few decades, some reviews on structure-based, catalyst-based, and bioactivity-based studies have been released. In this focused review, we extensively surveyed recent examples of one-pot reactions, particularly in view of modular approaches. Thus, the contents are categorized as three major sections (two-, three-, and four-component reactions) according to the number of reagents that ultimately compose atoms of the core structures of 2-quinolones. The collected synthetic methods are discussed from the perspectives of strategy, efficiency, selectivity, and reaction mechanism.

Keywords: 2-quinolone; N-heterocycle; cascade; catalysis; drug; multi-component; one-pot.

Figure 1

Recent examples of functional molecules containing 2-quinolone scaffold.

Figure 2

Tautomerization between 2-quinolone and 2-hydroxyquinolone.

Figure 3

Overview of classical and recent approaches to 2-quinolones.

Scheme 1

Synthesis of 2-quinolones by Pd-catalyzed reaction of 2-iodoanilines.

Scheme 2

Synthesis of 4-aryl-2-quinolones through a sequential Heck reaction cyclization of methyl-β-(2-acetamidoaryl)acrylates 6 and aryl iodides 7.

Scheme 3

Synthesis of 4-aryl-2-quinolones through a sequential Heck reaction/amination process of β-(2-bromoaryl) acrylamides 10 with aryl iodides 11.

Scheme 4

Synthesis of 3-substituted 2-quinolones through a sequential Heck reaction/cyclization process of 2-iodoaniline 14 with dialkyl itaconates 15.

Scheme 5

Pd/NiFe₂O₄-catalyzed one-pot synthesis of 4-aryl-2-quinolone derivatives.

Scheme 6

Synthesis of 2-quinolones by tandem Pd(0)-catalyzed amination/aldol condensation of aryl halides with acetamides.

Scheme 7

Synthesis of N-hydroxyquinolin-2(1H)-ones through a sequential Buchwald-type amidation/cyclization process with PMB (p-methoxybenzyl)-protected N-hydroxyamides.

Scheme 8

Synthesis of 2-quinolinones by Pd-catalyzed C–S activation/aryne insertion/intramolecular C–N coupling reaction.

Scheme 9

Synthesis of quinolones by Pd-catalyzed oxidative annulation between acrylamides and aryne precursors.

Scheme 10

Synthesis of quinolin-2(1H)-ones by a Pd-catalyzed C–H activation/C–C bond formation/intramolecular cyclization reaction.

Scheme 11

Synthesis of 4-aryl-2-quinolones through a sequential Heck reaction/intramolecular amidation process of cinnamides possessing 2-(pyridin-2-yl)ethanamine with aryl iodides.

Scheme 12

Copper iodide-catalyzed synthesis of 2-quinolones via cascade reactions of 2-halobenzocarbonyls with 2-arylacetamides.

Scheme 13

Preparation of 3-amido-2-quinolones using a dendritic Cu powder.

Scheme 14

Radical cyclization toward substituted 2-quinolone derivatives.

Scheme 15

Synthesis of 2-quinolones via Cu-mediated C–H/N–H annulation.

Scheme 16

Synthesis of 3-aryl-2-quinolones by alkyne activation with Ag(I) catalyst.

Scheme 17

Ru-catalyzed annulation of anilides with acrylates or propiolates.

Scheme 18

Rh-catalyzed synthesis of 3,4-cycloalkaquinolones using N-alkoxyamides and boronic esters.

Scheme 19

Rh-catalyzed decarbonylative coupling reaction.

Scheme 20

Microwave-assisted, solvent-free synthesis of substituted 2-quinolones by reaction of o-aminoarylketones with esters.

Scheme 21

Ir-catalyzed cascade reaction using carbamoyl chlorides and internal alkynes.

Scheme 22

Ni–Al cooperative bimetallic catalysis with arylformamides and internal alkynes.

Scheme 23

Friedländer reaction by basic mesoporous catalysts.

Scheme 24

Friedländer reaction by bifunctional zeolites as Lewis and Brønsted acid catalyst.

Scheme 25

Synthesis of 3,4-disubstituted 2-quinolones by one-pot condensation promoted by microwave irradiation.

Scheme 26

DMAP-catalyzed cyclization of Boc-anhydride of 2-alkenylanilines.

Scheme 27

Formation of 2-quinolones in reaction between 4-nitroketones and hydrazines.

Scheme 28

Synthesis of quinolones by reaction of 2-substituted indoles with 2-nitroalkenes under PPA.

Scheme 29

DBU-promoted annulation using o-acetamidoacetophenones and carbon dioxide.

Scheme 30

Lactamization of 2-alkenylanilines toward substituted 3,4-substituted 2-quinolones.

Scheme 31

Palladium-catalyzed annulation of terminal alkynes.

Scheme 32

Palladium-catalyzed annulation of internal alkynes.

Scheme 33

Carbonylative [3+2+1] annulation by C–H activation.

Scheme 34

Annulation of N-substituted o-iodoanilines.

Scheme 35

Microwave-assisted carbonylative cyclization.

Scheme 36

Regioselective synthesis of 3-substituted 2-quinolone using Pd@PS.

Scheme 37

Cascade alkenyl aminocarbonylation and intramolecular aryl amidation.

Scheme 38

Synthesis of 4-aryl-2-quinolinones in the presence of CO₂ gas.

Scheme 39

C–H activation of anilines with alkynes and CO gas.

Scheme 40

Rh-catalyzed aerobic oxidative cyclization of simple anilines with internal alkynes.

Scheme 41

Synthesis of 2-quinolinone by Ir-catalyzed three-component reactions.

Scheme 42

Cu-powder-catalyzed one-pot synthesis of 3- and/or 4-substituted 2-quinolones.

Scheme 43

Synthesis of multisubstituted 2-quinolones via four-component reaction.

Scheme 44

McCluskey’s studies on four-component reaction.

Scheme 45

Preparation of 2-quinolones using four-component adduct via Heck reaction.

Scheme 46

π-Acid-catalyzed cyclization of four-component adducts containing alkynes.

Scheme 47

Preparation of indoloquinolones using four-component reaction and C–H activation.

Scheme 48

Synthesis of indoloquinolones via double N–H/C–H activation.

Scheme 49

Ligand-controlled regioselective synthesis of 3,4-fused-2-quinolones.