title: Iron(III)-Catalyzed Arylation of Spiro-Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles.
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 H2 O 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 Nav 1.7 (±)-XEN402, which is currently in a phase IIb clinical trial for the treatment of pain.
authors.affiliation: Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China.
authors.forename: Mupeng
authors.initials: M
authors.lastname: Luo
authors.affiliation: Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China.
authors.forename: Rongju
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China.
authors.forename: Linqian
authors.initials: L
authors.lastname: Yu
authors.affiliation: Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China. weiwg@sari.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. weiwg@sari.ac.cn.|School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China. weiwg@sari.ac.cn.
authors.forename: Wanguo
authors.initials: W
authors.lastname: Wei
keywords: cyclization; epoxide; iron; oxindole; spiro compounds