Sun Shuo, Jia Rulong, Zhou Xin, Wang Zhongyi, Rong Jian, Ni Chuanfa, Hu Jinbo
State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou, Henan, China.
Nat Commun. 2025 Aug 19;16(1):7731. doi: 10.1038/s41467-025-62834-3.
Difluoromethylene moiety has gained widespread applications in pharmaceuticals, agrochemicals, and materials owing to its augmented lipophilicity and being bioisosteric to ethereal oxygen. Possessing two orthogonal reactivity modes for bridging an electrophile and a radical acceptor to give gem-difluorides (R-CF-R), the efficient difluoromethylene radical anion synthon (diFRAS) has been long sought after. In this work, we successfully utilize the readily available difluoromethyl phenyl sulfone (PhSOCFH) to couple with electrophiles and radical acceptors, thereby enabling PhSOCFH to serve as a novel diFRAS in organic synthesis. The generation of radicals (•CFR) via visible light-promoted homolytic cleavage of C-S bonds in (phenylsulfonyl)difluoromethylated derivatives (PhSOCFR) is the linchpin in the diFRAS strategy to construct gem-difluorides (R-CF-R) with structural complexity.
由于二氟亚甲基部分增强的亲脂性以及与醚氧的生物电子等排性，它在药物、农用化学品和材料领域得到了广泛应用。高效的二氟亚甲基自由基阴离子合成子（diFRAS）长期以来一直备受关注，它具有两种正交的反应模式，可将亲电试剂和自由基受体连接起来生成偕二氟化物（R-CF₂-R）。在这项工作中，我们成功地利用易于获得的二氟甲基苯砜（PhSOCFH₂）与亲电试剂和自由基受体偶联，从而使PhSOCFH₂能够作为有机合成中的一种新型diFRAS。通过可见光促进（苯磺酰基）二氟甲基化衍生物（PhSOCFR）中C-S键的均裂产生自由基（•CF₂R）是diFRAS策略中构建具有结构复杂性的偕二氟化物（R-CF₂-R）的关键。
