Asymmetric amination of alkyl radicals with two minimally different alkyl substituents

• 成果类型: Article
• 署名作者: Zhang, Yu-Feng; Wang, Biao; Chen, Zheng; Liu, Ji-Ren; Yang, Ning-Yuan; Xiang, Jin-Min; Liu, Juan; Gu, Qiang-Shuai; Hong, Xin; Liu, Xin-Yuan
• 署名单位: Southern University of Science & Technology; Southern University of Science & Technology; Southern University of Science & Technology; Zhejiang University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11144
• DOI: 10.1126/science.adu3996
• 发表日期: 2025-04-18
• 页码: 283-291
• 关键词: effective core potentials; ab-initio pseudopotentials; molecular calculations; catalysis; energy; electron; cu; sulfinimines; ligands; halides

摘要

Differentiating between similar alkyl groups is a major challenge in asymmetric catalysis. Achieving enantiocontrol over unactivated prochiral alkyl radicals is even more difficult owing to their high reactivity and limited interactions with chiral catalysts. In this study, we report a copper-catalyzed asymmetric amination of unactivated prochiral secondary alkyl radicals, using specifically designed chiral anionic multidentate ligands in a radical substitution reaction. This approach efficiently produces highly enantioenriched alpha-chiral alkyl amines and facilitates the enantioselective formal synthesis of a series of important drug molecules. Mechanistic studies reveal that bulky peripheral modifications on the ligands help create a truncated cone-shaped chiral pocket, enabling precise enantiodiscrimination through steric hindrance and noncovalent interactions. This strategy holds broad potential for asymmetric transformations involving diverse unactivated prochiral alkyl radicals and nucleophiles.