Wu, Jianjun, Chen, Zhenyu, Barnard, Jonathan H, Gunasekar, Ramachandran, Pu, Chunyang, Wu, Xiaofeng, Zhang, Shiyu, Ruan, Jiwu and Xiao, Jianliang
(2022)
Synthesis of chiral piperidines from pyridinium salts via rhodium-catalysed transfer hydrogenation.
Nature Catalysis, 5 (11).
pp. 982-992.
|
Text
Nature Catalysis Manuscript Revised.pdf - Author Accepted Manuscript Download (1MB) | Preview |
Abstract
Chiral piperidines are widespread in natural products and drug molecules. However, effective methods for their synthesis from simple starting materials are scarce. Herein, we report a rhodium-catalysed reductive transamination reaction for the rapid preparation of a variety of chiral piperidines and fluoropiperidines from simple pyridinium salts, with excellent diastereo- and enantio-selectivities and functional group tolerance. Thus, key to this reaction is the introduction of a chiral primary amine under reducing conditions, which, in the presence of water, undergoes transamination with the pyridinium nitrogen moiety while inducing chirality on the ring. The method overcomes some notable shortcomings of asymmetric hydrogenation and traditional multistep synthesis, affording various highly valuable chiral piperidines, including those bearing reducible and coordinating functional groups, heterocycles and, importantly, fluorine. The transamination mechanism also allows for alkylated and 15N-labelled piperidines to be easily accessed. The reaction is easily scalable, with multi-hundred-gram scale demonstrated. [Figure not available: see fulltext.].
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 3405 Organic Chemistry, 34 Chemical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Oct 2022 08:31 |
| Last Modified: | 21 Jun 2024 06:11 |
| DOI: | 10.1038/s41929-022-00857-5 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165687 |
Altmetric
Altmetric
