Chemodivergent Tandem Radical Cyclization of Alkene‐Substituted Quinazolinones: Rapid Access to Mono‐ and Di‐Alkylated Ring‐Fused Quinazolinones

• Published in: Chemistry : a European journal Vol. 29; no. 46; pp. e202301390 - n/a
• Main Authors: Wu, Hong‐Li, Zhang, Wei‐Kang, Zhang, Can‐Can, Wang, Ling‐Tao, Yang, Wen‐Hui, Tian, Wen‐Chan, Ge, Guo‐Ping, Xie, Long‐Yong, Yi, Rongnan, Wei, Wen‐Ting
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.08.2023; Wiley Subscription Services, Inc
• Subjects: Alkenes; Alkylation; Aromatic compounds; Chemistry; Chemistry, Multidisciplinary; chemodivergent tandem radical cyclization; Cyclic compounds; Esters; green synthesis; metal- and base-free; Nitriles; Oxidants; Oxidizing agents; Physical Sciences; Quinazolinone; Quinazolinones; remote para-C−H alkylation; Science & Technology; Substitutes; Synthesis; FUNCTIONALIZATION; ANNULATIONS; remote para-C-H alkylation; HETEROCYCLES; metal- and base-free; CASCADE CYCLIZATION; chemodivergent tandem radical cyclization; green synthesis; 1,N-ENYNES; remote para-C−H alkylation
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202301390

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 conditions, 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, whereas the di‐alkylated ring‐fused quinazolinones is mainly achieved through crucial steps of resonance 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. A novel method for preparing mono‐ and di‐alkylated ring‐fused quinazolinones from alkene‐substituted quinazolinones via chemodivergent tandem radical cyclization under metal‐ and base‐free conditions has been established.