Enantioconvergent Cu-Catalyzed Radical C–N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
| Autor: | Qiang-Shuai Gu, Cheng Luan, Li-Lei Wang, Fu-Li Wang, Xin-Yuan Liu, Juan Liu, Ning-Yuan Yang, Jiang-Tao Cheng, Zhong-Liang Li, Yu-Feng Zhang, Xiao-Yang Dong |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal of the American Chemical Society. 143:15413-15419 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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