Cai Yuan, Ye Xiaodong, Liu Sheng, Shi Shi-Liang
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2019 Sep 16;58(38):13433-13437. doi: 10.1002/anie.201907387. Epub 2019 Aug 7.
Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C-H alkylation of polyfluoroarenes with alkenes is described. The reaction employs bulky chiral N-heterocyclic carbene (NHC) ligands for nickel catalysts to enable exclusive activation of C-H bonds over C-F bonds and complete endo-selective C-H annulation and excellent enantioselectivity. A wide variety of chiral fluorotetralins, compounds otherwise difficultly accessed but serve as important bioisosteric analogs of both tetralin and heterocycle units for drug design, are expediently synthesized from easily available substrates. To our knowledge, this is the first example of catalytic enantioselective C-H functionalization of polyfluoroarenes.
手性多氟芳烃衍生物是化学领域一种重要的骨架结构。本文描述了一种前所未有的多氟芳烃与烯烃的对映选择性C-H烷基化反应。该反应使用大位阻手性N-杂环卡宾（NHC）配体修饰镍催化剂，从而实现C-H键相对于C-F键的选择性活化，以及完全的内型选择性C-H环化反应和出色的对映选择性。多种手性氟代四氢萘类化合物，这类化合物通常难以获得，但在药物设计中作为四氢萘和杂环单元重要的生物电子等排体类似物，可方便地从易得的底物合成。据我们所知，这是多氟芳烃催化对映选择性C-H官能团化的首例。
