Wang Shuaishuai, Li Tingrui, Gu Chengyihan, Han Jie, Zhao Chuan-Gang, Zhu Chengjian, Tan Hairen, Xie Jin
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 200032, Shanghai, China.
Nat Commun. 2022 May 4;13(1):2432. doi: 10.1038/s41467-022-30176-z.
Aromatic tertiary amines are one of the most important classes of organic compounds in organic chemistry and drug discovery. It is difficult to efficiently construct tertiary amines from primary amines via classical nucleophilic substitution due to consecutive overalkylation. In this paper, we have developed a radical tandem C-N coupling strategy to efficiently construct aromatic tertiary amines from commercially available carboxylic acids and nitroarenes. A variety of aromatic tertiary amines can be furnished in good yields (up to 98%) with excellent functional group compatibility under mild reaction conditions. The use of two different carboxylic acids also allows for the concise synthesis of nonsymmetric aromatic tertiary amines in satisfactory yields. Mechanistic studies suggest the intermediacy of the arylamine-(TPP)Fe(III) species and might provide a possible evidence for an S2 (bimolecular homolytic substitution) pathway in the critical C-N bond formation step.
芳香叔胺是有机化学和药物研发中最重要的有机化合物类别之一。由于连续过度烷基化，通过经典亲核取代从伯胺高效构建叔胺具有一定难度。在本文中，我们开发了一种自由基串联C-N偶联策略，可从市售羧酸和硝基芳烃高效构建芳香叔胺。在温和的反应条件下，各种芳香叔胺能够以良好的产率（高达98%）得到，且具有出色的官能团兼容性。使用两种不同的羧酸还能以令人满意的产率简洁地合成不对称芳香叔胺。机理研究表明芳胺-(TPP)Fe(III)物种的中间体存在，并可能为关键C-N键形成步骤中的S2（双分子均裂取代）途径提供可能的证据。
