化学
烷基
立体中心
有机化学
对映选择合成
胺化
卤化物
催化作用
药物化学
小学(天文学)
炔丙基
恶唑啉
组合化学
天文
物理
作者
Yufeng Zhang,Xiaoyang Dong,Jiangtao Cheng,Ning‐Yuan Yang,Lilei Wang,Fuli Wang,Liang Cheng,Juan Liu,Zhongliang Li,Qiang‐Shuai Gu,Xinyuan Liu
摘要
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.
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