Facile synthesis of aryl-substituted pyridines via Suzuki–Miyaura approach

• Published in: Tetrahedron 2015-11, Vol.71 (47), p.8943-8952
• Main Authors: Karadeniz, Eda, Zora, Metin, Kılıçaslan, Nihan Zülay
• Format: Article
• Language: English
• Subjects: Arylpyridine; Coupling; Ferrocene; Iodopyridine; Pyridine; Suzuki–Miyaura reaction
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.09.063

A facile and efficient synthetic route to arylpyridines is reported. When heated with boronic acids in the presence of 5 mol% PdCl2(PPh3)2 and KHCO3 in 4:1 DMF/H2O solution at 110 °C, 5-iodopyridines have undergone Suzuki–Miyaura coupling reactions to afford 5-aryl-substituted pyridines in good to excellent yields. The coupling reaction has been found to be general for a broad range of iodopyridines and boronic acids, and demonstrated good tolerance to a variety of aliphatic, aromatic, heteroaromatic and ferrocenyl groups with electron-withdrawing and electron-donating substituents. This coupling approach could accommodate various functional groups and provide rapid access to a library of functionalized arylpyridines of pharmacological interest. The starting 5-iodopyridines have been prepared from α,β-alkynic ketones, involving conjugate addition of propargylamine to alkynones, followed by metal-catalyzed cross-coupling of the resulting N-propargylic β-enaminones with aryl iodides and electrophilic cyclization with molecular iodine. [Display omitted]