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Dynamic Kinetic Resolution-Based Asymmetric Hydrogenation of Pyridines
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DOI：10.1021/jacs.6c10641.png)
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Abstract
En 中文
Chiral piperidines are ubiquitous in pharmaceuticals; yet their efficient and stereocontrolled synthesis from simple precursors remains challenging. Direct asymmetric hydrogenation of pyridines is an ideal strategy but is impeded by the intrinsic stability of the aromatic ring, catalyst deactivation, and difficulty of controlling multiple stereocenters. Existing methods often require preactivation and are largely limited in their scope and stereochemical diversity. Here, we report an iridium-catalyzed dynamic kinetic resolution (DKR) strategy that enables the direct asymmetric hydrogenation of racemic C2-substituted pyridines without preactivation. Central to this advance is the in situ generation of hydrogen iodide, which transiently activates the pyridine and enables efficient catalytic turnover. The reaction proceeds under simple conditions, accommodates a broad range of substrates, and delivers chiral piperidines bearing both exo- and endocyclic vicinal stereocenters with excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr).
Keywords:
Dynamic kinetic resolution
Hydrogenation
Piperidines
Pyridines
Transfer reactions
Journal
IF:
15.6
Papers:
20.0W
Citations:
60.2W
Organization
Cited Papers