Light-promoted Nickel-catalyzed CN Coupling Reaction Of Halogenated Aromatic Hydrocarbons With Sulfonamides

Sulfonamides have significant application in the field of pharmaceutical chemistry and synthetic chemistry,because of their various biological activity,unique reactivity and potential medicinal value.The development of envirimental and efficient synthetic methods attractd great interest in chemical research.Compared with the traditional transition metal catalyzed cross-coupling reaction,the strategy through the synergistic action of a photocycle and nickel catalysis cross-coupling cycle,has attracted more attention due to its enviromental and efficient characteristics,which provides a new research idea for solving the problem of energy barrier limitation in the process of catalytic reduction process of nickel catalyst.In the first chapter of this paper,the important application and synthesis methods of sulfonamides were introduced.The existing synthesis methods of N-(hetero)aryl sulfonamides are as follows:tranditional synthesis methods,transition metal catalyzed coupling reaction,metal free synthesis strategy and new synthesis methods of photosensitized nickel catalysis.Based on the summary of the synthesis strategy,the scientific problems to be solved in the current research progress are put forward.In the second chapter,a cheap and stable divalent metal nickel salt was used to catalyze the C-N cross-coupling reaction of aryl bromides with primary sulfonamides,under the condition of light without additional photocatalyst.Through the screening of bases,solvents and ligands,the target compound was obtained in 90%yield.Under mild reaction conditions,a broad range of N-(hetero)aryl sulfonamides can be synthesized with execellent compatibility of functional groups.In addition,this method can be effectively used for the modification of the drug molecular precursors bromoestrone and bromoflumazenil,and can still maintain high yield in gram scale reaction.In the mechanism study,the reaction appears to proceed via a Ni?-Ni? catalytic cycle.Compared with the existing synthetic methods,the synthetic method reported in this paper has the following advantages:(1)the results show that the reaction cost can be effectively reduced by using the near ultraviolet light 390-395(nm)as the light source,without adding photocatalyst;(2)the mild and soluble organic amine as the base avoids the use of insoluble inorganic strong base,enhances the compatibility of functional groups,and makes the reaction possible in the application of flow chemistry in homogeneous reaction system;(3)successfully solving the C-N coupling reaction of ortho-hindered and electron-rich group of(hetero)aryl bromines,makes the synthesis strategy more universal.