Regioselective Amination Of Multiple Halogenated Pyridine

Twenty years have passed Since Buchwald groups issued the publication of amination reaction. During the two decades, numerous research groups come into this field and involve in this reaction. The substrate can contain more function groups and the mechanism is more clear and definite. Buchwald-Hartwig C-N cross coupling have become a part of name reaction. Palladium-catalyzed amination of aryl, vinyl and heteroaryl halides and pseudohalides has rapidly emerged as a valuable tool in the synthesis of pharmaceuticals, polymers and novel materials.The regioselective C-N coupling processes have been executed on poly-halogenated compounds(especially pyridine) in the synthesis of pharmaceutical agents. After regioselective amination, the remaining C-X can participate in following transformation, such as Suzuki, Sonogashira, Heck, and Buchwald-Hartwig coupling. This methodology will provide a new vision in designing of reaction route.Systematic study was performed on the regioselective amination of multiple halogenated pyridine(including 2,3-dibromopyridine, 2,4-dibromopyridine, 2,5-dibromopyridine, 2,6-dibromopyridine, 3,4-dibromopyridine and 3,5-dibromopyridine) in this thesis. After screening optimization of catalyst, ligand, base, solvent, and the ratio of substrate, We isolate the mono-amination product in 92% yield. All the products have been characterized by melting point, NMR and MS.