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

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 S-(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.

Automated summary

The CF2H moiety has significant potential in drug design and incorporating it into biologically active molecules is an efficient strategy for finding lead compounds and drug candidates. Quinoxalin-2-one is of great interest to pharmaceutical chemists and frequently occurs in natural products and bioactive compounds. This study presents a practical and efficient method for synthesizing 3-CF2H-quinoxalin-2-ones, which could facilitate the search for potential lead compounds and drug candidates.