Asymmetric Radical Oxysulfonylation Of Terminal Alkenes And Internal Alkenes

Transition-metal-catalyzed asymmetric difunctionalization of alkenes enables the expedite construction of two vicinal carbon–carbon/carbon–heteroatom chemical bonds and stereogenic centers from readily available alkene starting materials.Thus,it has been established as a powerful technique for the sustainable preparation of chiral complex organic molecules.Recently,very impressive advances have been achieved in the development of Cu-catalyzed radical-initiated asymmetric alkenes difunctionalization.Such reactions usually involve intermolecular addition of free carbon-or heteroatom-centered radicals to alkenes followed by asymmetric functionalization of the thus-generated alkyl radical intermediates with chiral metal species.These methods,however,are generally limited to terminal alkenes,while the use of internal alkenes for concomitant generation of two vicinal stereocenters across the C=C double bonds has proved very problematic.Herein,we have developed a general and efficient asymmetric radical oxysulfonylation of alkenes in β,γ-unsaturated ketoximes using copper(I)-cinchona alkaloid-based sulfonamide complex as a strong single-electron-reducing catalyst.This method exhibited a broad scope across a range of both terminal and internal alkenes as well as diverse(hetero)aryl-or alkyl-substituted sulfonyl chlorides under very mild conditions.Experimental and computational studies suggested a likely CuII–CuI catalytic cycle with efficient stereodiscrimination under Curtin-Hammett kinetic control.The sulfonyl-containing isoxazolines could undergo further transformations to provide valuable building blocks prevalent in numerous bioactive molecules.The sulfone group-containing chiral isoxazoline compound can be further transformed under mild conditions,providing chiral structural units that are ubiquitous in many biologically active molecules and drug molecules.In order to solve the problems of the asymmetric bifunctionalization of free-radical internal alkenes and overcome the previous difficulities in this field.In this paper,a new method for constructing two adjacent chiral center compounds with good diastereoselectivity and enantioselectivity was developed based on the CurtinHammett principle.The present strategy would open a new door for the precise control of diastereo-and enantioselectivities in the challenging asymmetric radicalinitiated difunctionalization of internal alkenes.