State Key Laboratory of Applied Organic Chemistry, School of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P.R. China.
Guangdong Provincial Key Laboratory of Distributed Energy Systems, College of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, P.R. China.
Org Lett. 2023 Jun 23;25(24):4456-4461. doi: 10.1021/acs.orglett.3c01361. Epub 2023 Jun 9.
We report a redox-neutral, visible-light-mediated difluoroalkylation of unactivated C(sp)-H bonds in amides via nitrogen-centered radicals triggered intramolecular hydrogen atom transfer. Notably, all types (tertiary, secondary, and primary) of γ-C(sp)-H bonds displayed excellent reactivity. This methodology presents a facile route for the regioselective introduction of α,α-difluoroketone fragments into organic molecules. Moreover, the resulting -difluoroketones can be readily converted to structurally diverse difluoro-containing molecules, offering broad potential applications in medicinal chemistry and chemical biology.
我们报告了一种通过氮中心自由基引发的分子内氢原子转移，实现酰胺中未活化的 C(sp)-H 键的氧化还原中性、可见光介导的二氟烷基化。值得注意的是，所有类型（叔、仲和伯）的γ-C(sp)-H 键都表现出优异的反应性。该方法为有机分子中α,α-二氟酮片段的区域选择性引入提供了一种简便的途径。此外，所得的-α,α-二氟酮可以很容易地转化为结构多样的含二氟化合物，在药物化学和化学生物学中有广泛的潜在应用。
