Research In C-N Bonds Formation Through Radical Reaction Under Metal-Free Condition

Nitrogen heterocyclic compounds widely existed in natural products and drug molecules and have remarkable physiological and pharmacological activities,which closely relates to industrial and agricultural production as well as human health.As we all know,the construction of C-N bonds is the key for the synthesis of nitrogen heterocyclic compounds.Therefore,organic synthesis workers have been striving for a greener and more efficient way to build C-N bonds.Recently,the construction of C-N bonds has been rapidly developed and a large number of methods have emerged,among which radical reaction is an effective strategy to construct C-N bonds.Transition metal-catalyzed radical reaction has drawn more and more attention due to its high reactivity.However,a series of problems such as expensive and toxic transition metal catalysts,hard to synthesize ligand restrict the application of this strategy to build C-N bonds.Therefore,it is a forward-looking topic in this field to find a new method for the synthesis of nitrogen heterocyclic compounds with mild and environment-friendly features through radical reactions under metal-free condition.Therefore,this review focuses on the construction of C-N bonds via radical reaction under metal-free condition,which mainly includes four aspects.?1?The recent progresses in the construction of C-N bonds via radical reaction under metal-free condition have been summarized.And these achievements are presented according to the different types of substrates,such as alkanes,olefins and alkynes as well as other types of substrates.?2?A new method was developed for the synthesis of isatin oxime derivatives by the coupling reaction between 2-oxindoles with tert-butyl nitrite in the aqueous phase at room temperature.This reaction gives a new approach for the synthesis of potential pharmacologically active isatin oxime derivatives because of its metal-free and mild reaction condition and excellent substrate suitability.?3?This protocol achieves selective nitration of 3-substituted-2-oxindoles and uses tert-butyl nitrite as the nitrating reagent which overcomes the disadvantage of low atomic economy,serious environmental pollution,and regional selection in traditional nitration.The reaction can synthesize applicable 3-nitro-2-oxindoles with low energy consumption at room temperature without any metal catalysts or additives.?4?A novel strategy for the amination of 3-substituted-2-oxindoles in water under metal-free condition has been established.Under the economy I₂/TBHP?tert-butyl peroxide?system,direct amination of alkyl amines and aryl amines is efficiently achieved via radical reaction,and a series of3-amino-2-oxindoles are synthesized in moderate to good yields.