Visible‐Light Induced Trifluoromethylation/Cyclization of Unactivated Alkene‐Bound Quinazolinones

• Published in: European journal of organic chemistry 2024-05, Vol.27 (17), p.n/a
• Main Authors: Zou, Luqian, Zhao, Hengyuan, Wang, Xinming, Dong, Jun, Yang, Chungang, Sun, Weiqing, Xu, Jianbin, Fan, Baomin
• Format: Article
• Language: English
• Subjects: Alkenes; free radical reaction; Organic chemistry; oxidant-free; Oxidizing agents; photocatalysis; quinazolinone; Quinazolinones; Reagents; Substrates; TFAA
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202400056

Herein, we reported a selective, mild method for the visible‐light‐photocatalyzed trifluoromethylation and cyclization of unactivated tethered alkenes to provide tri‐ and tetracyclic quinazolinones. Trifluoroacetic acid and anhydride are inexpensive and readily available reagents for the process that proceeds without the addition of a strong oxidant. The wide substrate scope and the formation of 5‐ and 6‐membered rings are demonstrated in 44–82 % yields. Control experiments provide the basis for a proposed mechanism involving photocatalyzed SET from fac‐Ir(ppy)3 to TFAA and trifluoromethyl radical‐mediated regioselective cyclization. The practicality of the protocol was illustrated by a gram‐scale synthesis in 76 % yield. A trifluoromethylation cyclization of unactivated alkenes attached to quinazolinone scaffolds is demonstrated under visible light photocatalysis using readily available and inexpensive trifluoroacetic acid and anhydride, without the need for strong oxidants. A wide substrate range and cyclization to 5‐ and 6‐membered rings has been demonstrated in 44–82 % yields.