Visible-Light-Induced Radical Cross-Coupling To Construct C(sp~3)-C(sp~3) For The Synthesis Of Unnatural α-Amino Acid Derivatives

Due to the variety of structures and good biological activities,unnaturalα-amino acids have been widely studied and applied in the fields of medicinal chemistry,biochemistry and material science.Therefore,it is important to develop synthesis methods to rapidly construct unnaturalα-amino acids.Traditional methods mostly rely on transition metal catalysis,or use equivalent and even excess of chemical oxidants.Nearly a decade,with the development of photocatalysis,using photocatalytic radical coupling reaction to modify glycineα-C-H has becoming an effective method to synthesize unnaturalα-amino acids,this method is green and good functional tolerance under mild reaction conditions,but the atomic economy of the developed method is not enough,radical precursor needs to take off NHPI,I^-,Br^-or pyridine,to generate radical involved in coupling,and asymmetric synthesis method is rarely reported.Cyclopropane compounds are a class of multifunctional synthon,in which the cyclopropyl ketones can act as a radical precursor under photocatalytic conditions,and can open the ring to form radicals under reduction,so it is valuable for the synthesis of unnaturalα-amino acids.In the second chapter,we investigated the light-induced radical cross-coupling reaction of phenylcyacetone and N-phenylglycine to synthesize unnaturalα-amino acid derivatives.Through the optimization of conditions,with fac-Ir（ppy）₃ as the photosensitizer,Li BF₄ as Lewis acid and DMAP as the base,the product was obtained in THF in the presence of blue LED.Later,we demonstrated that each component is indispensable through a series of control experiments,and through the mechanism verification experiments,we proved that the reaction is performed through radical pathway.In the third chapter,the photocatalytic binding transition metal catalytic mode is used to achieve the chiral control of the reaction for the synthesis of chiral unnaturalα-amino acids.The chiral bisphosphine ligands can be used as both a photosensitiser and a chiral catalyst when coordinated with copper.To enhance the interaction between chiral photocatalyst and substrate,we added auxiliary groups containing nitrogen atoms,introduced a strong coordination site,screening chiral bisphosphonate ligands and preliminary condition optimization,to obtain the product with 61%yield,-56%/-61%ee,and lowered the reaction temperature to-10 ^oC,the enatioselectivity of the prouct could up to-80%/-71%ee,but only achieved 16%yield.