Dihydroquinazolinones as Photocatalyst-Free Carbamoyl Radical Precursors for Ynamide Formation

Abstract

A photocatalyst-free, visible-light-enabled alkynylation of carbamoyl radicals has been developed, facilitating streamlined access to alkynyl amides (ynamides). We use readily prepared carbamoyl-functionalized dihydroquinazolinone precursors, which undergo aromatization-driven C-C bond cleavage after blue light illumination to yield carbamoyl radicals that can be easily trapped by ethynylbenziodoxolone (EBX) reagents. Unlike many carbamoyl-radical alkynylation protocols, this transformation can be easily converted without additional photocatalysed and can be applied to the tertiary, secondary, primary amide precursors, as well as different alkynyl- and alkynyl substitutional BI reagents. Synthetic utility is highlighted by late installation of alkynyl amides at N-terminus of amino acids and oligopeptides and the derivatization of structurally complex bioactive molecules. Scale-up and subsequent diversification of terminal ynamides illustrate the practicality of this procedure. Mechanistic studies are consistent with a visible-light-induced radical mechanism involving ground-state EDA-complex formation and carbamoyl-radical generation.