Copper-Catalyzed Ring-Opening and Asymmetric Radical Transformations of Cycloketoxime Esters

Author:Wang Tao

Supervisor:wang xi sheng


Degree Year:2019





Asymmetric radical transformations can be realized effectively by the combination of transition-metal catalysis and radical chemistry.This dissertation mainly describe the synthesis of chiral dinitriles through radical-mediated ring-opening C-C bond cleavage and asymmetric cyanation or arylation.As for ring-opening of cyclobutanone oxime esters,the driving force of C-C bond cleavage is intrinsic ring strain,and the reaction can be carried out under single copper catalysis.As for less-strained cyclopentanone oxime esters,the reactions need to proceed under cooperative photoredox and copper catalysis.First chapter of this dissertation is about research background.On the one hand,we introduce transition-metal-catalyzed asymmetric radical transformations.The transition metals involved in this kind of reaction mainly include nickel,copper,cobalt,manganese,iron and so on.On the other hand,photo-promoted asymmetric radical transformations catalyzed by transition metals are described.Some of the reactions require additional photocatalyst.And in some reactions,transition metal complexes can act as photocatalyst.In the second chapter,we introduce the synthesis of chiral 1,3-dinitriles through copper-catalyzed ring-opening C-C bond cleavage and asymmetric cyanation of cyclobutanone oxime esters.The reaction featured mild conditions,high catalytic reactivity,good functional group compatibility and excellent enantioselectivity.To demonstrate the utility of this protocol,the 1,3-dinitrile was further converted to chiral pentanediamide or pentanediamine.Mechanistic studies indicated that the benzylic radical intermediate was involved in the reaction pathway.In the work of third chapter,we developed photoredox/copper co-catalyzed ring-opening C-C bond cleavage and asymmetric cyanation of cyclopentanone oxime esters to synthesize chiral 1,4-dinitriles.Under light condition,photocatalyst had high reduction potential,which led to formation of imine radical by reduction and subsequent C-C bond cleavage effectively.The reaction proceeded under room temperature,with catalyst loading only 2 mol%.And the reaction had demonstrated good functional group tolerance and excellent enantioselectivity.With the application of Ritter reaction or reduction reaction,the product could be transformed to chiral hexanediamide or hexanediamine.The radical capture experiment indicated that the benzylic radical intermediate existed in the reaction pathway.In the work of fourth chapter of this dissertation,we realized copper-catalyzed ring-opening of cyclobutanone oxime esters and asymmetric arylation.The arylation reagent used in the reaction was cheap and easily available arylboronic acid.Moderate to good yields and enantioselectivity were obtained in the reaction.The main issue of asymmetric arylation was slow transmetallation of arylboronic acid with copper,which led to the rate mismatch of C-C bond cleavage and transmetallation.Rhodium-catalyzed C-H alkynylation of Nmethylsulfoximines is described in the fifth chapter of this dissertation.The method realized C-H alkynylation of diaryl sulfoximines as well as that of S-alkyl S-aryl sulfoximines.The reaction showed good functional group compatibility and was easy to operate.The cross-coupling reactions were applied to derivatizations of the alkynylated product to synthesize multi-functionalized sulfoximines.The removal of protecting group of alkyne proceeded smoothly to give terminal alkyne.