Practical asymmetric hydrogenation of tetrasubstituted cyclic enamides for enantioenriched 3-amino-4-methylpiperidines.
- 1Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology Shenzhen 518055 China [email protected] [email protected] [email protected].
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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BibTeX
@article{chen2026practical,
title = {{Practical asymmetric hydrogenation of tetrasubstituted cyclic enamides for enantioenriched 3-amino-4-methylpiperidines.}},
author = {Qishu Chen and Qin Feng and Xiuxiu Li and Congcong Yin and Xumu Zhang},
journal = {Chemical science},
year = {2026},
month = oct,
doi = {10.1039/d6sc05491a},
url = {https://europepmc.org/article/MED/42904087},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Practical asymmetric hydrogenation of tetrasubstituted cyclic enamides for enantioenriched 3-amino-4-methylpiperidines.
AU - Qishu Chen
AU - Qin Feng
AU - Xiuxiu Li
AU - Congcong Yin
AU - Xumu Zhang
PY - 2026
DA - 2026/10/15
JO - Chemical science
DO - 10.1039/d6sc05491a
UR - https://europepmc.org/article/MED/42904087
AB - 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.
SN - 2041-6520
SN - 2041-6539
ER -