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Updated: Oct 24, 2026

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Practical asymmetric hydrogenation of tetrasubstituted cyclic enamides for enantioenriched
Qishu Chen1, Qin Feng1, Xiuxiu Li1
1Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology Shenzhen 518055 China lixx7@sustech.edu.cn yincc@sustech.edu.cn zhangxm@sustech.edu.cn.
Abstract:
Chiral 3-amino-4-methylpiperidines are valuable structural motifs in biologically active molecules, yet their efficient asymmetric synthesis remains challenging. We developed a Rh/JosiPhos-catalyzed asymmetric hydrogenation of tetrasubstituted cyclic enamides that provides direct access to enantioenriched 3-amino-4-methylpiperidines under exceptionally mild conditions with an H2 balloon at room temperature. A broad range of substrates was well tolerated, affording the corresponding products in up to 96% yield and 99% ee. The catalytic system showed high efficiency, achieving a turnover number of 10 000 on gram scale. The utility of the method was further demonstrated by the preparation of a key intermediate for the formal synthesis of tofacitinib. This practical and scalable protocol provides efficient access to chiral 3-amino-4-methylpiperidines and expands the scope of asymmetric hydrogenation of highly substituted enamides.
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