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Cu-Catalyzed Tandem C-N and C-C Bond Formation Leading to 4(1H)-Quinolones: A Scaffold with Diverse Biological Properties from Totally New Raw Materials in a Single Step

Satyanarayana Tummanapalli*, Kali Charan Gulipalli, Srinu Bodige, Anil Kumar Pommidi, Ravi Boya, Suresh Choppadandi, Mahendar Reddy Bakangari, Shiva Kumar Punna, Srinivas Medaboina, Devender Yadav Mamindla, Ashok Kanuka, Srinivas Endoori, Vijay Kumar Ganapathi, Sainath Dharmavaram kottam, Dinesh Kalbhor, Muralikrishna Valluri

*Curia India Pvt. Ltd, Plot # 9, MN Park, Turkapally, Shameerpet, Genome Valley, RR District, Hyderabad 500078, India, Email: Satyanarayana.Tummanapallicuriaglobal.com

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.

DOI: 10.1021/acs.joc.3c02215


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Abstract

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.

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proposed mechanism



Details

The article discusses a novel Cu-catalyzed tandem C−N and C−C bond-formation reaction to synthesize 2-substituted-4-(1H)-quinolones, which are significant in medicinal chemistry due to their diverse biological properties. Traditional methods for synthesizing 4-quinolones have limitations, such as requiring incompatible functional groups or expensive metals. The new method uses aryl boronic acid (or pinacolate ester) and nitriles as raw materials, with a cheap Cu-catalyst and O2 (air) as a green oxidant, making it environmentally friendly and cost-effective. The protocol was successfully applied to synthesize various natural products, including the first formal total synthesis of punarnavine. The proposed mechanism involves the formation of an aryl nitrilium ion, followed by intramolecular C−C bond formation. The method was optimized using different Cu catalysts and bases, achieving high yields. This new approach offers a simpler, more stable, and versatile method for constructing 4-quinolone scaffolds, potentially accelerating the development of new bioactive compounds for antibacterial and anticancer drug discovery. The study highlights the importance of developing modern synthetic methods to overcome the limitations of traditional approaches and expand the scope of starting materials for 4-quinolone synthesis.


Key Words

4(1H)-Quinolones, Oxygen


ID: J42-Y2024