Fenton‐Like Catalysis: Fe(III)/H2O2‐Mediated Oxidative Scission of Ascorbic Acid to a Sustainable One‐Carbon Approach for Aza‐Heterocycle Synthesis

We report a sustainable and efficient strategy for the synthesis of aza‐heterocycles via oxidative C─C bond cleavage of naturally occurring L‐ascorbic acid, utilized as a renewable one‐carbon (C₁) synthon. The transformation is promoted by a Fenton‐like Fe(III)/H₂O₂ catalytic system and exhibits broad functional group tolerance. A wide variety of substituted o‐aminobenzamides were successfully converted into quinazolinone derivatives in moderate to excellent yields. Additionally, other aza‐heterocycles derived from ortho‐substituted anilines were synthesized in moderate yields. The practicality of this protocol was further demonstrated through a one‐pot synthesis starting from isatoic anhydride 1′ and aromatic amines, along with successful gram‐scale reactions. Radical inhibition experiments with TEMPO and control studies in the absence of o‐aminobenzamide support a radical‐mediated oxidative pathway. Furthermore, the in situ formation of glyceraldehyde as a key C₁ intermediate was confirmed by HRMS, providing support for the proposed mechanism. Thus, this method offers an economical and scalable route for the construction of valuable nitrogen‐containing heterocycles from bio‐based feedstocks.