Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling to Access Chiral α-Amino-β-lactams

Jing-Jing Zheng; Wei-Long Liu; Qiang-Shuai Gu; Zhong-Liang Li; Ji-Jun Chen; Xin-Yuan Liu

doi:10.1021/prechem.3c00084

Copper-Catalyzed Enantioconvergent Radical C(sp³)-N Cross-Coupling to Access Chiral α-Amino-β-lactams

Precis Chem. 2023 Oct 10;1(10):576-582. doi: 10.1021/prechem.3c00084. eCollection 2023 Dec 25.

Authors

Jing-Jing Zheng^{1

2}, Wei-Long Liu^{1

2}, Qiang-Shuai Gu³, Zhong-Liang Li³, Ji-Jun Chen^{1

2}, Xin-Yuan Liu^{1

2}

Affiliations

¹ Shenzhen Key Laboratory of Cross-Coupling Reactions, Southern University of Science and Technology, Shenzhen 518055, China.
² Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.
³ Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Abstract

A copper-catalyzed enantioconvergent radical C(sp³)-N cross-coupling of racemic tertiary α-bromo-β-lactams with aromatic amines is developed under mild thermal reaction conditions. The use of a sterically demanded oxazoline-derived sulfonamide N,N,N-ligand is crucial for the reaction initiation and effective enantio-discrimination of the azetidinone-derived cyclic alkyl radicals. The strategy provides an attractive approach to access chiral α-amino-β-lactams, an important structural motif in many biologically active molecules. Preliminary mechanistic studies support the formation of azetidinone-derived alkyl radicals from the L*Cu(I)-amido complex and α-bromo-β-lactams.