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.