Copper‐Catalyzed Enantioselective Radical Desymmetrizing Cyclization of Cyclopentenes: Access to Chiral 2‐Azabicyclo[2.2.1]Heptan‐3‐ones

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‐azabicyclo[2.2.1]heptan‐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.