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Iron(III)‐Catalyzed Arylation of Spiro‐Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles
Author(s) -
Luo Mupeng,
Yuan Rongju,
Liu Xuesong,
Yu Linqian,
Wei Wanguo
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601185
Subject(s) - regioselectivity , friedel–crafts reaction , chemistry , catalysis , yield (engineering) , dichloromethane , phenols , oxindole , combinatorial chemistry , medicinal chemistry , organic chemistry , materials science , solvent , metallurgy
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 FeCl 3 ⋅6 H 2 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 Na v 1.7 (±)‐XEN402, which is currently in a phase IIb clinical trial for the treatment of pain.