Cu-Catalyzed Tandem C–N and C–C Bond Formation Leading to 4(<i>1H</i>)-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 B. Kalbhor, Muralikrishna Valluri
Abstract
A novel Cu-catalyzed tandem C–N and C–C bond-formation reaction has been developed to furnish 2-substituted-4-( 1H )-quinolones. 4-( 1H )-quinolones play an important role in medicinal chemistry. Many 2-aryl(alkyl)-4(1 H )-quinolones are found to exhibit diverse biological properties. While traditional methods have inherent issues [like starting materials with incompatible functional groups (NH 2 and keto groups)], many modern methods either require activated starting materials (like Ynones) or employ expensive metals (Pd, Rh, Au, etc.) involving carbonylation using CO or metal complexes. Our protocol presents an environmentally friendly one-step method for the construction of these useful 2-substituted-4-( 1H )-quinolones from easily available aryl boronic acid (or pinacolate ester) and nitriles as new raw materials, using a cheap Cu-catalyst and O 2 (air) as a green oxidant. We further extended its application to the synthesis of various natural products, including the first formal total synthesis of punarnavine. A plausible mechanism involving an aryl nitrilium ion (formed due to the intermolecular C–N bond-forming coupling between aryl boron species and the nitrile group) followed by tandem intramolecular C–C bond formation has been proposed.