A Homo‐Mannich Reaction Strategy Enables Collective Access to Ibophyllidine, Aspidosperma, Kopsia, and Melodinus Alkaloids

• Published in: Angewandte Chemie 2023-09, Vol.135 (37), p.n/a
• Main Authors: Jiang, Dan, Tang, Peng, Xiong, Hongbing, Lei, Shuai, Zhang, Yulian, Zhang, Chongzhou, He, Ling, Qiu, Hanyue, Zhang, Min
• Format: Article
• Language: English
• Subjects: Alkaloids; Aspidosperma; Asymmetric synthesis; Asymmetry; Chemistry; Cyclopropanol; Homo-Mannich Reaction; Ketones; Natural Products; Total Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202307286

We report here a homo‐Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, to construct a tricyclic hydrocarbazole core, which is shared by a variety of monoterpenoid indole alkaloids across families. Through this approach, an all‐carbon quaternary stereogenic center as well as an allyl and a ketone group were installed. Using this functionalized hydrocarbazole as the structural platform, D ring and E rings of different sizes (i.e., five‐, six‐, and seven‐membered) were successively or simultaneously assembled, leading to a collective asymmetric synthesis of seven alkaloids belonging to the ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloid families. A homo‐Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, has been developed to construct a tricyclic hydrocarbazole core. This approach enables a collective asymmetric synthesis of ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloids having either a five‐, six‐, or seven‐membered E ring.