Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones

• Main Authors: Kai-Zhong Fu (Author), Xu-Xin Chen (Author), Ya-Shi Zhao (Author), Yuan-Qing Gu (Author), Guo-Kai Liu (Author)
• Format: Book
• Published: MDPI AG, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph15121552; 1424-8247
• Keywords: 3-CF₂H-quinoxaline-2-ones; difluoromethylation; <i>S</i>-(difluoromethyl)sulfonium salt; fluorine-containing pharmaceuticals; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 15, Iss 12, p 1552 (2022)

CF₂H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF₂H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF₂H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and <i>S</i>-(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.