Iron(III)-Catalyzed Arylation of Spiro-Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles

Mupeng Luo; Rongju Yuan; Xuesong Liu; Linqian Yu; Wanguo Wei

doi:10.1002/chem.201601185

Iron(III)-Catalyzed Arylation of Spiro-Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles

Chemistry. 2016 Jul 4;22(28):9797-803. doi: 10.1002/chem.201601185. Epub 2016 May 31.

Authors

Mupeng Luo^{1

2

3}, Rongju Yuan^{1

2

3}, Xuesong Liu¹, Linqian Yu¹, Wanguo Wei^{4

5

6}

Affiliations

¹ Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China.
² University of Chinese Academy of Sciences, Beijing, 100049, China.
³ School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China.
⁴ Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210, China. weiwg@sari.ac.cn.
⁵ University of Chinese Academy of Sciences, Beijing, 100049, China. weiwg@sari.ac.cn.
⁶ School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China. weiwg@sari.ac.cn.

PMID: 27244669
DOI: 10.1002/chem.201601185

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.

Keywords: cyclization; epoxide; iron; oxindole; spiro compounds.