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Updated: May 23, 2025

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Enantioselective Total Synthesis of (-)-Vallesamidine Enabled by Asymmetric Hydrogenation and Aza-Wacker Cyclization
Fan Yang1, Xia-Lin Wang1, Feng-Kai Zhao1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
Abstract:
An enantioselective total synthesis of (-)-vallesamidine is described, integrating asymmetric hydrogenation with aza-Wacker cyclization to form the chiral spirocyclopentane-1,2'-indoline. Intramolecular Stetter reaction and alkylation are employed to construct a tetracyclic framework featuring a chiral quaternary carbon center. Schmidt rearrangement and intramolecular aldol condensation facilitate the formation of the D and E rings. This synthesis achieves (-)-vallesamidine in 14 steps in an overall yield of 4.2% from an exocyclic enone ester.
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