T-BuONa-Mediated Direct C-H Halogenation Of Electron-Deficient (Hetero) Arenes

(Hetero)aromatic halides are essential building blocks in natural products,pharmaceutical compounds and organic molecular materials.?Hetero?aromatic halides are widely used in organic material chemistry and pharmaceutical chemistry.The corresponding halides can be converted to other functional groups,for example,through transition metal-catalysed cross-coupling reactions,in which new carbon–carbon and carbon–heteroatom bonds are built.Quite a few of classical cross-coupling reactions such as the Heck reaction,the Suzuki reaction and the Buchwald–Hartwig reaction require aryl halides as the starting materials.Hence,it is always an important task to develop efficient preparation methods of?hetero?aromatic halides.There are a variety of known methods for the preparation of haloarenes from aromatics,especially from electron-rich systems.However,electron-deficient?hetero?arenes are difficult to be halogenated,often suffering from harsh conditions,such as strong alkyllithium bases at extremely low temperature or relatively weak bases upon heating,multi-steps and low yields.Among all the halogenated aromatics,aryl iodides are less accessible and particularly expensive due to the poor electrophilic nature of iodine.This paper presents an efficient halogenation method of electron-deficient?hetero?arenes.The reaction utilizes common and inexpensive halogen source perfluorobutyl iodide?C₄F₉I?,carbon tetrabromide?CBr₄?or carbon tetrachloride?CCl₄?as the readily-available halogenating agents,respectively.Sodium tert-butoxide as the catalyst for iodination or a promoter for bromination and chlorination,?hetero?aromatic halides are synthesized efficiently.The protocol features high efficiency,easy operating,matal-free,mild conditions,broad scope and gram scalability.An ionic pathway involving halogen bond activation and halophilic attack is proposed.Furthermore,the utility of the resulting iodinated heteroarenes is demonstrated in visible light-mediated,metal-free and photocatalyst-free cross-coupling reaction with?hetero?arenes to construct C_heteroaryl?C_aryl bond.