Synthesis of α-(Fluorophenyl)pyridine by Palladium-Catalyzed Cross-Coupling Reaction

✍ Scribed by Mao-Liang XU; Zhong-Wei AN; Ge-Yang WANG; Rui ZHOU; Wei-Song DU

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 64 KB
• Volume: 26
• Category: Article
• ISSN: 0256-7660
• DOI: 10.1002/cjoc.200890195

✦ Synopsis

A series of α-(fluoro-substituted phenyl)pyridines have been synthesized by means of a palladium-catalyzed cross-coupling reaction between fluoro-substituted phenylboronic acid and 2-bromopyridine or its derivatives. The reactivities of the phenylboronic acids containing di-and tri-fluoro substituents with α-pyridyl bromide were investigated in different catalyst systems. Unsuccessful results were observed in the Pd/C and PPh 3 catalyst system due to phenylboronic acid containing electron-withdrawing F atom(s). For the catalyst system of Pd(OAc) 2 /PPh 3 , the reactions gave moderate yields of 55%-80%, meanwhile, affording 10%-20% of dimerisation (self-coupling) by-products, but trace products were obtained in coupling with 2,4-difluorophenylboronic acids because of steric hinderance. Pd(PPh 3 ) 4 was more reactive for boronic acids with sterically hindering F atom(s), and the coupling reactions gave good yields of 90% and 91% without any self-coupling by-product.