Acidic C─H Functionalization to Access Ketoalkyl-Substituted Quinazolinones by Visible-Light Photoredox Catalysis

Herein, we report a novel visible-light-mediated radical cascade for the synthesis of ketoalkyl-substituted fused quinazolinones. This green and highly efficient method employs a readily available iridium photocatalyst and utilizes acetone as both the reaction medium and a C3-building block, enabled by a benzoyl peroxide (BPO)-mediated activation strategy for its α-acidic C─H bond. Contrary to the conventional wisdom that electrophilic oxygen-centered radicals preferentially abstract hydridic C─H bonds, our strategy operates via a distinct pathway that selectively targets acidic C─H bonds. This protocol is compatible with a wide variety of N-cyanamide alkenes as well as other ketones and activated methylene compounds (e.g., esters, acetonitrile, nitromethane). Mechanistic studies, including radical trapping experiments, kinetic isotope effect (KIE) measurements, and Stern–Volmer quenching studies are conducted to support proposed mechanism.