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Access to Multifunctionalized Benzofurans by Aryl Nickelation of Alkynes: Efficient Synthesis of the Anti‐Arrhythmic Drug Amiodarone
Author(s) -
Iqbal Naeem,
Iqbal Naila,
Maiti Debabrata,
Cho Eun Jin
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201909015
Subject(s) - chemistry , alkyne , benzofuran , aryl , regioselectivity , combinatorial chemistry , intramolecular force , organic chemistry , alkyl , catalysis
An unconventional nickel‐catalyzed reaction was developed for the synthesis of multifunctionalized benzofurans from alkyne‐tethered phenolic esters. The transformation involves the generation of a nucleophilic vinyl Ni II species by the regioselective syn ‐aryl nickelation of an alkyne, which then undergoes an intramolecular cyclization with phenol ester to yield highly functionalized 1,1‐disubstituted alkenes with 3‐benzofuranyl and (hetero)aryl substituents. The methodology can be used for the late‐stage benzofuran incorporation of various drug molecules and natural products, such as 2‐propylvaleric acid, gemfibrozil, biotin, and lithocholic acid. Furthermore, this arylative cyclization method was successfully applied for the efficient synthesis of the anti‐arrhythmic drug amiodarone.