Synthesis of Heteroarylated Pyridines via a Double C−H Bond Functionalization using Palladium‐catalyzed 1,4‐Migration Combined with Direct Arylation

Abstract

The C−H bond functionalization of pyridyl C3‐position of 4‐arylpyridines using Pd 1,4‐migration has been investigated. Under suitable reaction conditions, oxidative addition of 4‐(2‐bromoaryl)pyridines to palladium followed by a Pd 1,4‐migration activates these pyridyl C3‐positions. Next, the Pd‐catalyzed coupling via C−H bond activation of the heteroarenes affords the C3‐heteroarylated 4‐arylpyridines. The new C−C bond created in this coupling reaction results from the functionalization of two C−H bonds. For this coupling reaction, a bromo‐substituent on the aryl unit of 4‐arylpyridines was employed as a traceless directing group. This heteroarylation method tolerates a range of substituents on the benzene ring as well as several heteroarenes. Moreover, from 3‐arylpyridines, C2‐ or C4‐functionalization of the pyridine ring also proved possible. In addition, this procedure uses an air‐stable catalyst and an inexpensive base.