Nickel-catalyzed Intramolecular Nucleophilic Addition Of Vinyl-halides To ?-ketoamides

Organohalides are important coupling partners as electrophiles in the transition-metal catalyzed bond-forming reactions.Recently,their usage as nucleophiles has drawn much attention,and based on this concept some new synthetic methods have been developed.However,the study in this field is still in its infancy and the reactions are limited to aryl bromides or iodides.The nucleophilicity of vinyl halide was studied in an intramolecular addition reaction to a-ketoamimde in this dissertation.The intramolecular nucleophilic addition of vinyl bromides to a-ketoamides was first studied with N-(2-bromoallyl)-2-oxo-N,2-diphenylacetamide as model substrate.By systematic optimizations of solvent,temperature,ligand,and catalyst precursor,the standard reaction was found to give the best result(82%yield)with 5 mol%NiCl2(PCy3)2,2.0 eq.Me2Zn as reductant,and 25 ? in 1,4-dioxane.The substrate scope was subsequently examined.Furthermore,it was found that the reaction of vinyl chloride could proceed well when the reaction temperature was improved to 50 ? and good results were obtained for the reactions of a series of substrates.New catalyst system was then under consideration in order to avoid the use of Me2Zn,which is toxic and flammable,as well as the formation of a byproduct resuled from the Negishi coupling reaction of the substrate and Me2Zn.Gratifyingly,when the above reaction was carried out in the presence of 10 mol%NiBr2(dppe),2.75 eq.zinc dust,at 75 ? in the mixed solvent of THF and CH3CN with a volume ratio of 7 to 1,95%yield of the desired product was isolated.And the optimum conditions were successfully extended to other substrates.In this dissertation,20 new compounds were synthesized and characterized by1H NMR,13C NMR spetrums and MS(HRMS)analysis.