Efficient Synthesis of Quinoxaline Derivatives via PIDA-Promoted Oxidative Annulation

Abstract

Quinoxaline derivatives represent an important class of privileged heterocyclic scaffolds widely present in natural products and biologically active molecules. Herein, we report a novel and efficient one pot, two step oxidative annulation strategy for the synthesis of quinoxalines via Phenyliodine (III) diacetate (PIDA)-mediated transformation of acetophenones/ phenyl acetylene derivatives with 1,2-diamines. This protocol utilizes inexpensive and readily available starting materials and proceeds through in situ formation of phenyl glyoxal, followed by condensation and subsequent aromatization. The method exhibits broad functional group tolerance and delivers the desired quinoxaline derivatives in high yields. Notably, PIDA serves as a transition metal-free and cost-effective oxidizing agent, highlighting the practicality and sustainability of the approach. Furthermore, this methodology enables the synthesis of biologically active compounds such as AG 1295, a PDGFR inhibitor that suppresses cell proliferation, and DPQ, a PARP inhibitor that disrupts DNA repair and induces cell death. Overall, the synthesized quinoxalines serve as valuable intermediates with promising applications in natural product synthesis and medicinal chemistry.