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

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

Jing-Jing Zheng  1   2 , Wei-Long Liu  1   2 , Qiang-Shuai Gu  3 , Zhong-Liang Li  3 , Ji-Jun Chen  1   2 , Xin-Yuan Liu  1   2
Affiliations

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

Jing-Jing Zheng et al. Precis Chem. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Enantioconvergent C(sp3)–N Cross-Coupling to Access Chiral α-Amino-β-lactams
Scheme 2
Scheme 2. Mechanistic Investigation
See this image and copyright information in PMC

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