Wang Hang, Zhou Chunlin, Gao Zezhong, Li Shangda, Li Gang
Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian, 350002, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2023 May 8;62(20):e202300905. doi: 10.1002/anie.202300905. Epub 2023 Apr 5.
Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C-H functionalization is unknown and enantioselective direct iodination of inert C-H bond is very rare. Rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry. Herein, we report an unprecedented highly enantioselective isodesmic C-H functionalization to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with Pd catalysis. Importantly, further transformations of the enantioenriched products are readily available at the iodinated or the Weinreb amide position, paving the way of related studies for synthetic and medicinal chemists.
同键反应是其他需要强氧化剂或高活性中间体的化学转化反应的温和替代方法。然而，对映选择性同键C-H官能化反应尚不存在，而惰性C-H键的对映选择性直接碘化反应也非常罕见。手性芳基碘化物的快速合成对于合成化学具有重要意义。在此，我们报道了一种前所未有的高度对映选择性同键C-H官能化反应，通过去对称化和动力学拆分，利用钯催化制备手性碘化苯乙酸Weinreb酰胺。重要的是，对映体富集产物在碘代或Weinreb酰胺位置易于进行进一步转化，为合成化学家和药物化学家的相关研究铺平了道路。
