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Manganese-Catalyzed Asymmetric Hydrogenation of Pyridyl Cyclic <i>N</i>-Alkyl Imines: A Direct Route to <i>S</i>-Nicotine and Derivatives

Jitao Yang, Yanan Guo, Zheng Wang, Yizhou Wang, Dexin Fu, Qingbin Liu, Gregory A. Solan, Yanping Ma, Wen‐Hua Sun

2025Organic Letters11 citationsDOI

Abstract

The asymmetric hydrogenation (AH) of cyclic N -alkyl imines offers an elegant and efficient method to afford chiral amines, especially for S -nicotine and its derivatives. However, this approach remains an ongoing challenge due to undesirable coordination of pyridyl-containing substrates to the active metal catalyst. Herein, we disclose a manganese-catalyzed AH that allows access to S -nicotine and other chiral α-(hetero)aryl pyrrolidines and provides an example of a base–metal catalyst that displays superior performance to its noble metal counterparts.

Topics & Concepts

ChemistryCatalysisAlkylManganeseNicotineAsymmetric hydrogenationOrganic chemistryMedicinal chemistryCombinatorial chemistryEnantioselective synthesisBiologyNeuroscienceAsymmetric Hydrogenation and CatalysisAsymmetric Synthesis and CatalysisCatalytic C–H Functionalization Methods