Study On The Reation Based On Photocatalytic Radical Remote Migration Strategy And Asymmetic C-H Functionalization

Visible light catalyzed oxidation-reduction catalysis has become a mild and powerful catalytic method,and the combination of photocatalysis with other catalytic modes is increasingly favored by synthetic chemists.Based on this idea,we have started research on the photoredox distant radical transfer strategy and asymmetric C-H functionalization reactions,which mainly include two parts of work.(1)Amino-heteroarylation of unactivated alkenes with organic photoredox catalysis to construct remote amino ketones.Amino ketones are widely present in natural products,drug molecules,and biologically active molecules,and the current strategies mainly focus on the synthesis of α-and β-amino ketones,but the synthesis of remote amino ketones is rarely studied.In this paper,unactivated alkenes were used as acceptors,and N-protected pyridinium salts were used as radical precursors to successfully achieve the visible light-catalyzed amino-heteroarylation reaction of unactivated alkenes,and a series of remote amino ketones were successfully constructed.Mechanistic verification experiments showed that the proton required for nitrogen radical generation comes from the solvent,and the group migration goes through a cyclic transition state.Due to the energy barriers of the tetra-membered ring and heptamembered ring transition states being higher than those of the three-membered,five-membered,and six-membered ring transition states,more unreacted products are obtained.In addition,other migrating groups such as cyano,pyridine,(Benz)thiazole,and(Benz)oxazole can also be successfully migrated,and chirality attempts were made through acid-assisted group migration.(2)Combination of light and nickel catalysis to achieve α-asymmetric acylation of saturated nitrogen-containing heterocycles.Chiral amino ketones are important small molecule catalysts and pharmaceutical intermediates,and their synthesis depends more on the induced synthesis of metal reagents or chiral precursors.Direct C-H functionalization mainly relies on palladiumcatalyzed C-H aromaticization reactions.In this paper,N-protected pyrrolidine was used as the substrate,mixed anhydrides were used as the acyl source,and the strategy of adding hydrogen atom transfer reagents was adopted to achieve the light and nickel dual-catalyzed α-asymmetric acylation of saturated nitrogen-containing heterocycles.Ligand investigations confirmed that the BOX ligand is the optimal ligand skeleton,and the introduction of the cyanide-formed anionic ligand is beneficial to the improvement of the ee value,and finally,an ee value of 75% can be obtained.