Access to Multifunctionalized Benzofurans by Aryl Nickelation of Alkynes: Efficient Synthesis of the Anti‐Arrhythmic Drug Amiodarone

Abstract

Abstract 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.