Sustainable assembly of quinazolinones via iodine-mediated/catalyzed methods: a decennial update on transition-metal-free approaches

Quinazolinone, a promising N-heterocyclic framework, often exists in a broad range of natural products, alkaloids, and US FDA-approved drugs. Moreover, quinazolinone-directed C(sp2)-H and C(sp3)-H functionalizations under transition-metal (Ru, Rh, Pd)-catalyzed conditions are important in the regioselective synthesis of bioactive products. Owing to the flexible redox behavior of iodine under photochemical, electrochemical, and iodine-peroxide-based conditions, quinazolinones have been assembled over the years through iodine-based annulations, oxidative cyclizations, and intramolecular C–N couplings from readily available anilines, 2-aminobenzamides, isatins, and isatoic anhydrides, etc. Existing literature reviews on the synthesis of quinazolinones are mainly focused on transition-metal-catalyzed approaches, leaving I2-based, metal-free strategies underrepresented. Herein, we present a systematic survey of I2 and in situ generated I2-based preparation of quinazolinone derivatives (quinazolin-4(3H)-ones, 2,3-fused quinazolinones, dihydroquinazolinones) under I2-mediated, I2-O2-mediated, I2-peroxide-mediated, I2-PPh3₃-mediated, photochemical, electrochemical, and miscellaneous conditions (from 2016 to present). The novel strategies discussed in this report possess notable merits such as transition-metal-free conditions, one-pot operations, gram-scale experiments, etc. Reaction conditions, limitations, representative examples, mechanisms, and post-synthetic applications are highlighted wherever applicable. Overall, we expect that the iodine-based synthetic advancements discussed in this report would enable expansions in this field by serving as a comprehensive reference tool.