Graduate School of Science and Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube, Yamaguchi, 755-8611, Japan.
Angew Chem Int Ed Engl. 2023 May 15;62(21):e202301343. doi: 10.1002/anie.202301343. Epub 2023 Apr 17.
Herein, we report a copper-catalyzed stereospecific fluorination involving CsF and α-bromocarboxamides as tertiary alkyl sources that, unlike traditional stereospecific routes involving stereoinversive S 2 reactions, proceeds with retention of stereochemistry. The developed stereospecific Cu-catalyzed reaction is among the most efficient methods for synthesizing fluorinated molecules that possess highly congested stereogenic carbon centers. Mechanistic studies revealed that the combined reactivity of CuF and Cs salt is essential for completing the catalytic cycle. Our catalytic system underwent fluorination exclusively with tertiary alkyl bromides and did not react with primary alkyl bromides, indicating that this stereospecific fluorination methodology is suitable for synthesizing fluorinated building blocks possessing stereo-defined F-containing tertiary carbon stereogenic center.
在此，我们报告了一种铜催化的立体特异性氟化反应，涉及 CsF 和 α-溴代酰胺作为叔烷基源，与涉及立体反转 S 2 反应的传统立体特异性途径不同，该反应以立体化学的保留方式进行。所开发的立体特异性 Cu 催化反应是合成具有高度拥挤的立体手性碳原子的氟化分子的最有效方法之一。机理研究表明，CuF 和 Cs 盐的组合反应性对于完成催化循环至关重要。我们的催化体系仅用叔烷基溴进行氟化，而不与伯烷基溴反应，这表明这种立体特异性氟化方法适用于合成具有立体定义的 F 取代的三级碳立体手性中心的氟化砌块。
