Copper‐Catalyzed Enantioconvergent Radical C(sp3)−N Cross‐Coupling: Access to α,α‐Disubstituted Amino Acids

• Published in: Angewandte Chemie International Edition 2023-07, Vol.62 (27), p.e202302983-n/a
• Main Authors: Zhang, Yu‐Feng, Wang, Jia‐Huan, Yang, Ning‐Yuan, Chen, Zheng, Wang, Li‐Lei, Gu, Qiang‐Shuai, Li, Zhong‐Liang, Liu, Xin‐Yuan
• Format: Article
• Language: English
• Subjects: Amino acids; Ammonia; Asymmetric Catalysis; Construction; Copper; Cross coupling; Enantiomers; Halides; Nitrogen; Nucleophiles; Tertiary Alkyl Halides; Unnatural Amino Acids
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202302983

Transition‐metal catalyzed enantioconvergent cross‐coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α‐disubstituted amino acids. However, the construction of chiral C−N bonds between tertiary‐carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper‐catalyzed enantioconvergent radical C−N cross‐coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N‐ligand with a long spreading side arm. An array of α,α‐disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α‐fully substituted amine building blocks. A copper‐catalyzed enantioconvergent radical C−N cross‐coupling of tertiary alkyl halides with sulfoximines (as ammonia surrogates) was realized by employing a chiral anionic N,N,N‐ligand with a long spreading side arm under mild conditions. An array of valuable α,α‐disubstituted amino acids could be furnished with good efficiency (up to 95 % yield) and enantioselectivity (up to >99 % ee).