College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Shandong Normal University, 88 Wenhuadong Road, Jinan 250014, China.
Shanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling, Shanxi 712100, China.
Molecules. 2018 Aug 31;23(9):2207. doi: 10.3390/molecules23092207.
In this article we demonstrate how asymmetric total synthesis of ()-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap -hydroxyacetophenone, through esterification, asymmetric reductive amination, -diphenylmethyl deprotection and reductive amination, to provide the final ()-rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetric reductive amination, catalysed by the iridium⁻phosphoramidite ligand complex and helped by some additives, the readily prepared 3-acetylphenyl ethyl(methyl)carbamate directly reductively coupled with diphenylmethanamine to yield the chiral amine product in 96% and 93% yield.
在本文中，我们展示了如何通过直接不对称还原胺化作为关键转化，在 4 步反应中实现（）-利伐斯的明的不对称全合成。该路线以易得且廉价的对羟基苯乙酮为起始原料，经酯化、不对称还原胺化、-二苯甲基脱保护和还原胺化，以 82%的总收率和 96%的对映选择性得到最终的（）-利伐斯的明。在不对称还原胺化反应中，使用手性铱-磷酰胺配体催化剂，并添加一些添加剂，可使易于制备的 3-乙酰基苯基乙基（甲基）氨基甲酸酯直接与二苯甲胺还原偶联，以 96%和 93%的收率得到手性胺产物。
