Chemoselective Synthesis of Quinazoline and Quinazolinone Derivatives via NH4I-Mediated Oxidative Annulation Under Metal- and Additive-Free Conditions

Abstract

Owing to the structural importance and synthetic value of quinazoline and quinazolinone scaffolds in drug discovery, we herein report a novel NH₄I‑involved oxidative annulation of readily available 2,1‑benzisoxazoles/isatoic anhydrides with benzylic alcohols for the selective synthesis of these heterocycles. In this three‑component transformation, ammonium iodide serves as both an economical nitrogen source and a co‑oxidant, avoiding the use of additional additives. This metal‑ and additive‑free protocol enables precise cleavage of C─O/N─O bonds with simultaneous formation of C─N bonds in a single operation, exhibiting excellent chemoselectivity, atom economy, and broad functional group tolerance. Additionally, the resulting quinazoline and quinazolinone derivatives are efficiently transformed into high‑value analogues of bioactive molecules, underscoring the synthetic utility of the method.