- Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
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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 enantioenrichedN-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.
- Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
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supporting information
p. 15413 - 15419
(2021/09/30)
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- Highly diastereo- and enantioselective silver-catalyzed double [3+2] cyclization of α-imino esters with isocyanoacetate
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Presented herein is a new complexity-generating method in which both functionalities of α-imino esters undergo stereoselective cyclization with isocyanoacetates to produce directly linked oxazole-imidazolines, which can be transformed into highly functionalized α,β-diamino esters and imidazolinium salts in high diastereo- and enantiopurity. Double up: An unprecedented silver-catalyzed title reaction has been developed and provides access to directly linked oxazole-imidazolines. A highly diastereo- and enantioselective variant was also realized using the catalyst Ag/L*. The products can be easily transformed into highly functionalized chiral α,β-diamino esters or imidazolinium salts which are useful motifs in asymmetric synthesis and catalysis.
- Shao, Pan-Lin,Liao, Jia-Yu,Ho, Yee Ann,Zhao, Yu
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supporting information
p. 5435 - 5439
(2014/06/09)
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