Chemodivergent tandem radical cyclization of alkene substituted quinazolinones: Rapid access to mono- and di-alkylated ring-fused quinazolinones.

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene substituted quinazolinones under metal- and base-free system, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3)-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, while the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of spin delocalization and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3)-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.