Selective synthesis of pyridazine-fused chromones and 3-pyridazinyl chromones through intermolecular chromone annulation of o-hydroxyphenylenaminones with aryldiazonium salts

Abstract

Intramolecular chromone annulations of o-hydroxyphenylenaminones (o-HPEs) with a variety of C–H bond functionalization precursors have attracted much attention and become some of the most straightforward and efficient approaches for the rapid assembly of structurally diverse chromone compounds. However, the intermolecular chromone annulation reaction has not yet been developed. Herein, we report an unprecedented metal-free, chemodivergent and skeleton-controllable annulation reaction of o-HPEs with aryldiazonium salts. This protocol features a new intermolecular chromone annulation strategy for the divergent synthesis of pyridazine-fused chromones and 3-pyridazinyl chromones via adjusting the reaction temperature. Moreover, the pyridazine-fused chromones exhibit promising high antiviral activity against human coronavirus OC43 (HCoV-OC43), with higher safety than the reference drug (Arbidol), indicating that the intermolecular chromone annulation methodology might provide assistance in drug discovery.