Enantioselective Synthesis of ε‐Lactams via Rh(I)‐Catalyzed C─C Bond Activation

Abstract ε‐Lactams are important structural motifs in medicinal chemistry, but a fully enantioselective synthesis without byproduct formation represents a challenge that has attracted significant research interest. Herein, we report an atom‐ and step‐economic synthesis of chiral ε‐lactams via Rh(I)‐catalyzed enantioselective C─C bond activation of aminocyclopropanes. The catalytic C─C bond activation enables a directed generation of chiral rhodacyclobutanes that circumvents β‐hydride decomposition. Subsequent enantioselective cycloaddition of the alkene unit and then fragmentation generates chiral ε‐lactams. A range of enantioenriched ε‐lactams have been obtained with excellent regio‐ and enantioselectivities, which can undergo several stereospecific transformations. Theoretical calculations are performed to reveal the reaction mechanism and the origin of enantioselectivity control.