Iron(III)‐Catalyzed Arylation of Spiro‐Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles |
| |
| Authors: | Mupeng Luo Rongju Yuan Xuesong Liu Linqian Yu Prof Wanguo Wei |
| |
| Affiliation: | 1. Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China;2. University of Chinese Academy of Sciences, Beijing, China;3. School of Life Science and Technology, ShanghaiTech University, Shanghai, China |
| |
| Abstract: | An efficient and highly regioselective iron(III)‐catalyzed Friedel–Crafts‐type arylation of spiro‐epoxyoxindoles with phenols was developed for rapid access to 3‐(3‐indolyl)‐oxindole‐3‐methanols, which could be further elaborated into benzofuranyl‐spirooxindoles under Mitsunobu conditions. When spiro‐epoxyoxindoles were reacted with naphthols in the presence of a catalytic amount of FeCl3?6 H2O in dichloromethane, they underwent a tandem Friedel–Crafts‐type arylation and O‐cyclization to yield novel naphthofuranyl‐spirooxindoles in excellent yields. This method is applied to enable the efficient and highly regioselective synthesis of a small‐molecule inhibitor of the sodium channel Nav1.7 (±)‐XEN402, which is currently in a phase IIb clinical trial for the treatment of pain. |
| |
| Keywords: | cyclization epoxide iron oxindole spiro compounds |
|
|
