Watchara Wimonsong and Sirilata Yotphan*
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty
of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.

Quinoxalin-2(1H)-one skeleton is one of the important structural motifs found in natural products, bioactive compounds and pharmaceuticals, known to display remarkably interesting physical and chemical properties as well as diverse biological activities. A number of quinoxalinones and their derivatives have been extensively employed in drug discovery, medicinal chemistry, organic synthesis, materials chemistry as well as agrochemical research. In recent years, the direct C‒H functionalization of quinoxalin-2(1H)-ones has been served as an ideal and efficient synthetic approach to afford substituted quinoxalin-2(1H)-ones. Among these reported protocols, the direct amination (C−N bond coupling) has drawn significant research interest from synthetic and medicinal chemists as the 3-amino-quinoxalin-2(1H)-one derivatives have been considered as an important subfamily with broad spectrum of biological and pharmacological activities such as anticancer, antimicrobial, antiviral and anti-inflammatory properties.
Herein, we report the PIDA-promoted direct C‒N bond coupling of quinoxalinones at C3 with N-heterocycles as nitrogen sources. This protocol features simple and mild metal-free conditions, high atom economy, employing readily available reagent, easy-to-handle experimental procedure, good to excellent product yields, together with broad substrate scope and good scalability. The present methodology provides a highly attractive and alternative approach to a preparation of a diverse range of 3-(azol-1-yl)quinoxalin-2(1H)-ones, which could be further employed in many applications. Acknowledgement: This work was supported by Thailand Research Fund (RSA6280024), the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research and Innovation, Central Instrument Facility (CIF), Faculty of Science, Mahidol University for providing research facilities, and Development and Promotion of Science and Technology Talent Project (DPST), the Institute for Promotion of Teaching Science and Technology for financial support through student scholarship to W.W.

Reference: PIDA-induced oxidative C-N bond coupling of quinoxalinones and azoles. Watchara Wimonsong and Sirilata
Yotphan*. Tetrahedron 81 (2021) 131919.