Microwave-Assisted Copper-Catalyzed One-Pot Synthesis of 2- Aryl/Heteroaryl-4-Quinolones via Sequential Intramolecular Aza- Michael Addition and Oxidation Priti Singh, [a] Santosh Kumar Sahoo + , [a] Nerella Sridhar Goud + , [a, b] Baijayantimala Swain, [a] Venkata Madhavi Yaddanapudi, [a] and Mohammed Arifuddin* [a, c] Abstract: A protocol has been developed that allows the synthesis of 2-aryl/heteroaryl-4-quinolones from readily avail- able, affordable starting materials. The reaction proceeds under microwave conditions with moderate to high yields in the presence of copper catalyst. Short reaction time, good functional group tolerance, high atom economy, non-toxic byproduct and no use of special ligands emphasize the applicability of this method in organic synthesis. Introduction 4-Quinolone and its derivatives are reckoned as privileged chemotypes that are embedded in a wide range of biologically and therapeutically active compounds. [1] Apart from pharma- ceuticals, various natural products also exemplify the presence of quinoline moiety in general and 4-quinolone scaffold in particular. [2] 4-Quinolone/Quinoline moiety is key in eliciting diverse biological activity like anti-tubercular, [3] antimalarial, [4] antibacterial (ciprofloxacin, levofloxacin, moxifloxacin), hypolipidemic, [5] antiviral, [6] xanthine oxidase inhibition, [7] and antimitotic effect [8] (Figure 1). Last five decades have witnessed widespread growth of 4-quinolone based antibiotics not only to combat common clinical pathogens but also to tackle resistant bacterial infection due to their potent, broad-spectrum, bacter- icidal activity. [9,10] Although with time, novel modifications in 4-quinolone scaffold have generated more potent antibacterial congeners to uphold its status of go-to antibiotic, however, their synthesis remains challenging that demands straightforward innovation and efficient protocol. Various synthetic protocols have been reported previously for the formation of 2-substituted-4-quinolones. [11] Most com- mon method of it involves condensation of anilines with β-keto esters followed by cyclization of the formed β-arylaminoacry- lates by classical approaches like Conrad-Limpach and Niemen- towski reactions, [12] base-promoted cyclization of N- (ketoaryl)amides (the Camps cyclization). [13] However, these reactions require harsh conditions like high temperature, strong acids that significantly limits its application. Further strategies include non-traditional synthetic method utilizing transition metals such as palladium-catalysed carbon- ylation, titanium-mediated reductive coupling, and ruthenium- catalysed reduction reactions. Poor yield, long reaction time, pre-functionalization and harsh conditions used in these reactions calls for further optimization of reaction conditions. [a] P. Singh, S. Kumar Sahoo, + Dr. N. Sridhar Goud, + B. Swain, Dr. V. Madhavi Yaddanapudi, Dr. M. Arifuddin Department of Chemical Science, National Institute of Pharmaceutical, Education, and Research (NIPER), Balanagar, Hyderabad – 500037, Telengana State (India) [b] Dr. N. Sridhar Goud + Present Address: Molecular Imaging Branch, NIMH, National Institutes of Health (NIH), Bethesda – 20892 (USA) [c] Dr. M. Arifuddin Present Address: Synergy Community Welfare Research Center (SCWRC), Head office, Panacea, Synergy India Foundaion, 4th Floor, TSWREIS building, Masab Tank Hyderabad – 500028 (India) E-mail: arifabib@gmail.com yvmadhavi.niperhyd@gov.in [ + ] These authors contributed equally. Supporting information for this article is available on the WWW under https://doi.org/10.1002/ajoc.202200181 Figure 1. Representative therapeutic agents containing quinoline/quinolone moiety. Research Article doi.org/10.1002/ajoc.202200181 www.asianjoc.org Asian J. Org. Chem. 2022, e202200181 (1 of 7) © 2022 Wiley-VCH GmbH