Skeletal editing of anthranils O-to-CN transmutation: access to ring-expanded quinazolines

Abstract

Skeletal editing is a uniquely powerful tool in organic chemistry that simplifies the synthesis of complex molecules. Herein, we report a simple skeletal editing strategy of anthranils for the synthesis of quinazolines via O-to-CN transmutation, which utilizes diverse aldehydes (including alkyl, aryl, and heterocyclic) and amines (such as ammonium acetate and benzylamines) as carbon and nitrogen precursors. This method enables the synthesis of ring-expanded quinazolines through three distinct approaches under metal-free (even additive-free) conditions, and exhibits good chemoselectivity and broad functional group tolerance. Moreover, late-stage skeletal modification, preparation of pharmaceutical analogs, scaled-up synthesis, and derivatization of products further demonstrate the practicability of this strategy. Preliminary mechanistic studies reveal an atom replacement reaction involving a 6π-electrocyclization/dehydroaromatization or [4 + 2] cycloaddition/intramolecular ring-opening process.