Direct Palladium‐Catalyzed C5‐Arylation of 1,3,4‐Oxadiazoles with Aryl Chlorides Promoted by Bis(di‐isopropylphosphino) Ferrocene

Abstract

AbstractThe direct palladium‐catalyzed C−H arylation of 1,3,4‐oxadiazoles with challenging aryl chloride substrates is promoted by the use of a specifically designed electron‐rich ferrocenyl diphosphane. This protocol employs 0.5 to 1.0 mol % catalyst loading without any additives such as copper or ammonium salts, and equally tolerates electron‐donating and electron‐withdrawing substituents on the (heteroaryl)aryl halides, as illustrated by the efficient synthesis in 86 % yield of the anti‐tubercular agent PHOXPY (2‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)pyrazine) by a late‐stage arylation using 2‐chloropyrazine.