Enantioconvergent Cu-Catalyzed Radical C–N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
Yufeng Zhang, Xiaoyang Dong, Jiangtao Cheng, Ning‐Yuan Yang, Lilei Wang, Fuli Wang, Cheng Luan, Juan Liu, Zhong‐Liang Li, Qiang‐Shuai Gu, Xin‐Yuan Liu
Abstract
α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)–N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C–N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenriched N-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon–heteroatom formation strategy.