DOI: 10.1002/ange.202308836 ISSN:

An Asymmetric Hydrogenation/N‐Alkylation Sequence for a Step‐Economical Route to Indolizidines and Quinolizidines

Wei Zhao, Wenji Wang, Huan Zhou, Qishan Liu, Zhiqing Ma, Haizhou Huang, Mingxin Chang
  • General Medicine

The direct catalytic asymmetric hydrogenation of pyridines for the synthesis of piperidines remains a challenge. Herein, we report a one‐pot asymmetric hydrogenation of pyridines with subsequent N‐alkylation using a traceless Brønsted acid activation strategy. Catalyzed by the iridium‐BINAP complex, the substrates undergo ketone reduction, cyclization and pyridine hydrogenation in sequence to form indolizidines and quinolizidines. The absolute configuration of the chiral center of the alcohol is retained and influences the formation of the second chiral center. The experimental and theoretical mechanistic studies reveal that the chloride anion and certain noncovalent interactions govern the stereoselectivity of the cascade reaction throughout the catalytic process.

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