Visible-light-driven copper(ii) catalysis for 2,3-disubstituted quinazolinone synthesis via Ullmann N-arylation and C–H oxidative amidation

Abstract

A novel visible-light-driven method for the synthesis of 2,3-disubstituted quinazolinones has been developed, employing copper(II) as a catalyst in a sequential Ullmann N-arylation and C–H oxidative amidation process. This methodology utilizes o-iodo-N-substituted benzamides and benzylamines as substrates, with molecular oxygen sourced from ambient air functioning as the oxidant. The reaction is conducted under mild conditions, utilizing cost-effective copper(II) chloride as the catalytic agent and Eosin Y as a photosensitizer, facilitated by blue LED irradiation. A broad compatibility with various substrates is demonstrated, yielding products in the range of 30% to 84%. Additionally, mechanistic studies elucidate a single-electron transfer pathway that incorporates aryl radical intermediates. This research presents a sustainable and efficient strategy for the synthesis of quinazolinones, with considerable synthetic and mechanistic implications.