Catalytic Asymmetric Transformations Via Radical-Polar Crossover(RPC)

Radicals,also known as "free radicals",arc a class of unstable atoms or groups with unpaired electrons.Therefore,radical reactions usually have the characteristics of fast rate and high activity.Compared with the well-developed stereoselectivity control in traditional polar/ionic chemistry,asymmetric transformation of radicals has always been recognized as a very challenging problem.In the past decade,the vigorous development of visible-light catalysis has brought new opportunities for free radical chemistry.By combining visible-light catalysis with versatile chiral catalysts,chemists have realized a broad range of catalytic asymmetric radical transformations,including asymmetric radical coupling,asymmetric radical addition,asymmetric hydrogen atom transfer,and catalytic transformations via chiral metal-mediated.radical capture.Radical-polar crossover can convert radicals into polar/ionic intermediates to achieve better stereoselectivity control,but due to the compatibility issue with chiral catalysts,this field has not received widespread attention from chemists.Based on radical-polar crossover,this thesis aims to realize multicomponent asymmetric transformation of functionalized olefins using a combined catalyst system.By means of oxidative radical-polar crossover,we have developed a lightmediated asymmetric multicomponent dicarbofunctionalization of enamides in the presence of photoredox/chiral lithium phosphate combined catalysis,furnishing a wide range of chiral amine derivatives with high levels of enantiosclectivities.Mechanistic studies suggest that chiral lithium phosphate can serve as a pocket to accelerate the aggregation of enamide and RAE through hydrogen-bonding and coordination interaction,enabling the formation of a CTC.Either enamide or CTC can be excited by the direct irradiation or Ru(Ⅱ)-mediated energy transfer to furnish chiral iminium intermediate for asymmetric Friedel-Crafts reaction of indole.Based on reductive radical polar crossover,we have established the dicarbofunctionalization of electron-poor olefins using hydrogen atom transfer and palladium combined catalysis.Through a hydrogen atom transfer/radical addition/single-electron reduction relay process,aliphatic C-H addition to electronpoor olefins generates a carbanionic intermediate,which can be trapped by a πallylpalladium to give a three-component allylation product.This strategy can tolerate various alkanes,olefins and allylation reagents,being applicable to the formal synthesis of(±)-mesembrine.Based on reductive radical polar crossover,we also realized a nickel-catalyzed multicomponent asymmetric propargyl alkylation reaction by the combination of photocatalytic nucleophile generation and nickel-catalyzed asymmetric propargyl substitution reaction,giving a series of chiral propargyl derivatives with high levels of enantioselectivity.These results showcase the potential application of photocatalytic nucleophile generation in asymmetric transition metal catalysis.