Collective Total Syntheses of Five Lycopodium Alkaloids. Issue 32 (21st June 2022)

• Record Type: Journal Article
• Authors: He, Feifei; Feng, Shangbiao; Zhao, Yulong; Shi, Hongliang; Duan, Xiaoguang; Li, Huilin; Xie, Xingang; She, Xuegong
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-21
• Subjects: Cycloisomerization -- Decahydroquinolines -- Gold Catalysis -- Lycopodium Alkaloids -- Total Synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202205439
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: It is reported herein that by exploiting the commonly shared bicyclic decahydroquinoline motif, a gold‐catalyzed enamide–alkyne cycloisomerization reaction is developed to access tricyclic cores in a simple way. These tricyclic cores further serve as an advanced platform for the divergent enantioselective collective total syntheses of five Lycopodium alkaloids, belonging to three different structural types, in a concise and protecting‐group‐free fashion. The key transformations in the second phase include: 1) a transannular reductive Heck cyclization for installation of the azepane ring in fawcettidine, fawcettimine, and lycoposerramine Q; 2) a domino Mukaiyama hydration/Grob fragmentation process for construction of the ten‐membered lactam system in phlegmariurine B; 3) a Fukuyama one‐pot protocol for the construction of the 2‐pyridone motif in lycoposerramine R. The newly developed strategy is expected to pave the way for the synthesis of other structurally related Lycopodium alkaloids. Abstract : The collective total syntheses of five Lycopodium alkaloids were accomplished in an enantioselective and protecting‐group‐free manner. The syntheses included a gold‐catalyzed enamide–alkyne cycloisomerization and the establishment of skeletal diversification approaches at different reactive sites of the tricyclic skeleton to achieve divergent total syntheses of Lycopodium alkaloids.