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Synfacts 2025; 21(07): 737
DOI: 10.1055/a-2601-4270
Innovative Drug Discovery and Development

Dispersion Enables Asymmetric Amination of Near-Symmetric Carbon Radicals

Contributor(s):
Dirk H. Trauner
,
Aleksa Milosavljevic
Zhang Y-F, Wang B, Chen Z, Liu J-R, Yang N-Y, Xiang J-M, Liu J, Gu Q-S, Hong X *, Liu X-Y *. Southern University of Science and Technology, Shenzhen and Zhejiang University, Hangzhou, P. R. China
Asymmetric Amination of Alkyl Radicals with Two Minimally Different Alkyl Substituents.

Science 2025;
388: 283-291
DOI: 10.1126/science.adu3996
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Keywords

asymmetric amination - radicals - copper catalysis - N,N,P-ligands - sulfoximines

Significance

Nature has mastered the asymmetric synthesis of chiral amines, as evidenced by the widespread presence of amino acids. On the contrary, organic synthesis still struggles with this, often requiring chiral resolution of enantiomers, or multi-step synthesis employing amino acids as building blocks. In this work, Hong, Liu, and co-workers describe a copper-catalyzed asymmetric amination of near-symmetrical secondary alkyl iodides 1 to obtain amines 2 with high enantioselectivity and in good to excellent yields.


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Comment

In this reaction, the racemic secondary alkyl iodide 1 generates a radical that is captured by the nitrogen nucleophile (sulfoximine) 3 bound to the copper-ligand manifold (an outer-sphere mechanism). Dispersion interactions between the bulky N,N,P ligand (L1/L2) and the larger alkyl substituent (RL) deliver high enantioselectivity. The reaction works well at low temperatures, which results in high enantioselectivity, even when RS and RL are very similar substituents (i. e., having similar A-values, such as 2a). The reaction has a broad functional group compatibility (2b–i).


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Publication History

Article published online:
23 June 2025

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