Transition Metal-catalyzed Kumada Reaction Of Pyrimidinyl Tosylates And2-ethylthio-pyrimidine With Grignard Reagents

As an important and effective method for the construction of C-C bonds in organic chemistry, Kumada cross-coupling reactions were widely used in the synthesis of the molecules with medical, biological and material functions. Early reactions of Kumada coupling were generally catalysed by nickel or palladium. But these transition metals are expnsive and also endangers the environment. Therefore,more efforts were focused on developing new catalysts that are non-toxic and lower priced.In this thesis, we reviewed the latest progress developing the Kumada methods,and explored the cross-coupling reactions between Pyridine and Pyrimidine sulfonate with Grignard reagents. The contents of this thesis include:1) An Ferric chloride-catalyzed cross-coupling of Pyrimidin-2-yl sulfonates and pyridin-2-yl sulfonates with alkyl magnesium bromides is presented. The reaction proceeds at-10 o C ~-15 o C for 15 min, and THF/NMP as solvent without other special ligands. and the corresponding products are obtained with moderate to high yields. When aryl magnesium bromides were used as nucleophiles, the reactions were operated at-20 o C for 30 min, with [Fe(acac)3] as catalyst and THF as solvent, and with DMEDA as an additive. The reactions are fast, with the products easy to separate,therefore can be a new method for the preparation of these hetero aryl derivatives.2) A series of 2-(ethylthio)pyrimidine derivatives were reacted with Grignard reagents,with Pd(OAc)2 as catalyst, DPE-phos as the ligand at room temperature, with the products produced in good yields. Both alkyl magnesium bromides and aryl magnesium bromides were tolerated well. The reactions can be operated under mild conditions, with wide tolerance to the substrates and the products are easy to separate.Structure of the products above were confirmed by 1H NMR, 13 C NMR spectra and HRMS analysis.