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. 2025 Sep 8;64(37):e202509640.
doi: 10.1002/anie.202509640. Epub 2025 Jul 30.

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

Shiyuan Sui  1 , Hao Wu  1 , Yuanyuan Guo  1 , Gongming Chen  1 , Junbiao Chang  1 , Dachang Bai  1
Affiliations

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

Shiyuan Sui et al. Angew Chem Int Ed Engl. .

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.

Keywords: Aminocyclopropanes; C─C bond activation; Enantioselective; Rhodium; ε‐lactams.

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