Iodospirocyclization of Tryptamine‐Derived Isocyanides: Formal Total Synthesis of Aspidofractinine. Issue 46 (17th October 2018)

• Record Type: Journal Article
• Authors: Saya, Jordy M.; Roose, Thomas R.; Peek, Jarryt J.; Weijers, Bram; de Waal, Thomas J. S.; Vande Velde, Christophe M. L.; Orru, Romano V. A.; Ruijter, Eelco
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 46(2018)
• Page Start: 15232
• Page End: 15236
• Publication Date: 2018-10-17
• Subjects: Alkaloids -- cyclization -- isocyanides -- natural product synthesis -- spiroindolines; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201809678
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The N ‐iodosuccinimide‐mediated spirocyclization of tryptamine‐derived isocyanides to generate spiroindolenines is reported. The products contain both an imine and an imidoyl iodide as flexible handles for follow‐up chemistry. Nucleophilic addition typically occurs chemoselectively on the imine moiety with complete diastereoselectivity, providing opportunities for the construction of complex molecular frameworks. The synthetic potential of the method was showcased in the formal total synthesis of (±)‐aspidofractinine. Abstract : I make(s) spirocycles : Iodospirocyclization of tryptamine‐derived isocyanides affords highly substituted spiroindolenine imidoyl iodides. The imine functionality can undergo a variety of diastereoselective addition reactions, including in situ reduction, while the imidoyl iodide functionality is remarkable stable. The utility of the method was demonstrated by the formal total synthesis of (±)‐aspidofractinine.