Gao Zhaofeng, Liu Jingwen, Huang Haizhou, Geng Huiling, Chang Mingxin
Department of Chemistry, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi, 712100, P. R. China.
Angew Chem Int Ed Engl. 2021 Dec 20;60(52):27307-27311. doi: 10.1002/anie.202112671. Epub 2021 Nov 16.
Asymmetric reductive amination (ARA) is one of the most promising methods for the synthesis of chiral amines. Herein we report our efforts on merging two ARA reactions into a single-step transformation. Catalyzed by a complex formed from iridium and a steric hindered phosphoramidite, readily available and inexpensive aromatic ketones initially undergo the first ARA with ammonium acetate to afford primary amines, which serve as the amine sources for the second ARA, and finally provide the enantiopure C -symmetric secondary amine products. The developed process competently enables the successive coupling of inorganic and organic nitrogen sources with ketones in the same reaction system. The Brønsted acid additive plays multiple roles in this procedure: it accelerates the formation of imine intermediates, minimizes the inhibitory effect of N-containing species on the iridium catalyst, and reduces the primary amine side products.
不对称还原胺化反应（ARA）是合成手性胺最具前景的方法之一。在此，我们报告了将两个ARA反应合并为一步转化的研究成果。由铱和空间位阻亚磷酰胺形成的配合物催化下，易得且廉价的芳香酮首先与乙酸铵进行第一次ARA反应，生成伯胺，这些伯胺作为第二次ARA反应的胺源，最终得到对映体纯的C对称仲胺产物。所开发的方法能够在同一反应体系中实现无机和有机氮源与酮的连续偶联。布朗斯特酸添加剂在此过程中发挥多种作用：它加速亚胺中间体的形成，使含氮物种对铱催化剂的抑制作用最小化，并减少伯胺副产物。
