Copper-Catalyzed Intramolecular Cope-Type Hydroamination Of Nonactivated Olefins

Nitrone is one of the important skeletons of many natural products with biological activity,and it is also the intermediate of N-heterocyclic compounds and some important drug molecules.In addition,nitrone is often used as a spin trap in chemical reactions and for therapeutic purposes.Cyclic nitrones and their derivatives are also widely used in biochemistry,pharmaceutical chemistry and synthetic chemistry.Although nitrones have important applications in natural product chemistry and organic synthesis chemistry,according to the literature research,most of the previous methods for the synthesis of nitrones have the disadvantages of harsh reaction conditions(high temperature),low conversion rate and yield,and there are few reports that need metal catalysis in these methods,even for chirality There are less reports on the synthesis of cyclic nitrates.Our group has found the first case of intermolecular cope type hydroamination of oxime.The reaction undergoes a Cu(I)-catalytic cycle and has high efficiency and enantioselectivity.Based on the importance of nitrones in organic synthesis,we hope to use the appropriate metal and chiral catalyst system to realize the cope type asymmetric hydroamination in the non activated olefin molecules,and to synthesize highly functional multi substituted chiral cyclic nitrones.On the basis of our previous work,this paper reports the intramolecular cope type hydroamination of unsaturated alkenylketoxime catalyzed by Cu(I).In the racemization reaction,the unsaturated alkenylketoxime with different substituents was used as the substrate,and the corresponding nitrones were obtained in high yield.The conversion of high enantioselectivity was realized by ligand regulation,which provided a simple path for the synthesis of chiral cyclic nitrones.The method has the advantages of mild conditions,simple operation,good functional group compatibility,and high enantioselectivity.This strategy laid the foundation for the synthesis of chiral nitrones from alkenylketoxime.