Iron(III)‐Catalyzed Arylation of Spiro‐Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles. Issue 28 (31st May 2016)

• Record Type: Journal Article
• Authors: Luo, Mupeng; Yuan, Rongju; Liu, Xuesong; Yu, Linqian; Wei, Wanguo
• Is Part Of: Chemistry. Volume 22:Issue 28(2016)
• Page Start: 9797
• Page End: 9803
• Publication Date: 2016-05-31
• Subjects: cyclization -- epoxide -- iron -- oxindole -- spiro compounds; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201601185
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Spirooxindoles : A highly regioselective iron(III)‐catalyzed Friedel–Crafts‐type arylation/O‐cyclization of spiro‐epoxyoxindoles with phenols enables rapid access to spirooxindoles (see figure; DIAD=diisopropyl azodicarboxylate). These privileged structures are the basis of many biologically relevant compounds, and the 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, is reported.