Copper‐Catalyzed Enantioselective Radical Desymmetrizing Cyclization of Cyclopentenes: Access to Chiral 2‐Azabicyclo2.2.1Heptan‐3‐ones

Abstract We herein report an unprecedented copper‐catalyzed enantioselective radical desymmetrizing cyclization of cyclopentenes through peroxidation‐amination and alkylamination. This strategy provides a general and efficient route for the synthesis of chiral 2‐azabicyclo2.2.1heptan‐3‐ones bearing one quaternary and two adjacent tertiary stereocenters in good yields with high enantio‐ and diastereoselectivity. The embedded peroxy and amide motifs allow a diverse of transformations, furnishing a library of structurally diverse analogues, including all four stereoisomers of 6‐hydroxy derivatives. Mechanistic studies and density functional theory (DFT) calculations support the formation of a substrate‐Cu(II) complex and indicate that nucleophilic radical addition to the coordinated alkene is the key stereocontrolling step responsible for both enantioselectivity and diastereoselectivity.