Theoretical Study On Iron-Catalyzed C(sp~3)-H Amination Of Alkyl Azides

Transition metal catalyzed aliphatic C(sp³)-H bond amination reaction is the important reaction for the synthesis of pyrrolidine and its derivatives.From the microscopic and molecular levels,through the in-depth study of the structural properties and basic laws of the compounds in the catalytic reaction and related processes,chemists can understand the microscopic nature of catalytic reactions from multiple perspectives.It's also provide the theoretical basis for the improvement and design of new catalysts and chemical reactions with specific functions.In this paper,the intramolecular C(sp³)-H bond amination reaction of aliphatic azide catalyzed by the chelated iron complex was systematically studied by density functional theory calculation.Theoretical calculations show that the catalytic reaction is accomplished by the following path:First,the ligand exchanges with the substrate to obtain the reactive Fe(II)catalyst,which is oxidized by the substrate to Fe(III)imine radical and releases nitrogen.Second,the alkyl radical is obtained by intramolecule activation of C(sp³)-H.The target product was obtained by free radical rebonding,and the catalytic cycle was completed.Boc₂O is used for the amine group protection in the reaction to ensure the re-release of the catalyst.The system is almost inactivated without the addition of Boc₂O.Therefore,the role of Boc₂O as an additive in the catalytic cycle is studied in this paper.The experimental results of this catalytic reaction show the highly chemical selectivity:iron-catalyzed C(sp³)-H amination normally yield the five-membered pyrrolidine product.However,as the chain length between the vinyl group and the azide group increases,the reaction results in six-membered ring product.As the chain length between the vinyl group and the azide group continues to increase,the reaction product remains five-membered pyrrolidine.In response to this characteristic,theoretical studies have found that,the size of the product ring is determined by the activation sites of the substrate and the difference of the active sites is determined by the electronic and spatial effects of the corresponding transition states.Finally,metal iron is highly spin in the catalyst,transition state and intermediates in the mechanism study.This paper reveals the mechanism,activity and selectivity of an important class of iron-catalyzed C(sp³)-H bond amination reactions at the molecular level.The research results will provide theoretical guidance and prediction for optimizing and designing new catalysts and catalytic systems.