Iodospirocyclization of Tryptamine‐Derived Isocyanides: Formal Total Synthesis of Aspidofractinine

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.N ucleophilic addition typically occurs chemoselectively on the imine moiety with complete diastereoselectivity,p roviding opportunities for the construction of complex molecular frameworks. The synthetic potential of the method was showcased in the formal total synthesis of (AE)-aspidofractinine.

Total Synthesis of Aspidosperma and Strychnos Alkaloids through Indole Dearomatization

“…In addition to Michael acceptors, other electrophiles proved suitable in similar cascade processes . We have reported N ‐iodosuccinimide (NIS) as a compatible electrophile in iodospirocyclization reactions . The resulting products, especially regarding the imidoyl iodide moiety, are remarkably flexible and can undergo a range of post cyclization modifications.…”

Total Syntheses of (−)‐Minovincine and (−)‐Aspidofractinine through a Sequence of Cascade Reactions

“…Aspidofractinine is thought to originate from 9 that is derived from minovincine through ester hydrolysis followed by decarboxylation (Scheme 1). [1,16] While several routes have been developed to construct racemic aspidofractinine, [23,24] its only asymmetric synthesis was reported by Gagnon and Spino [25] in 2009. The relative ease of our minovincine synthesis served as an impetus for developing a biosynthetically inspired synthesis of (À)-aspidofractinine (6).…”

Hydrogen-Bonding-Promoted Cascade Rearrangement

“…级联反应是开展天然产物全合成和合成砌块构建 的重要方法 [1] , 其中基于异腈的级联反应为杂环化合物 的制备提供了非常有用的途径 [2] . 色胺衍生的异腈, 也 就是在吲哚的 3-位碳上安装了一个链状异腈的吲哚化 合物, 在串联反应中展示了极为高效的反应特性, 作为 初始原料已经被用于若干串联反应来构建螺环吲哚啉 化合物, 相关级联反应研究取得了极大的成功 [3][4][5][6][7] . 然 而, 基于色胺衍生异腈的反应模式和反应产物的多样性 仍然比较有限, 因此围绕 3-(2-异氰乙基)吲哚开发更多 的新反应仍然是一个挑战性的科学问题和迫切需要开 展的工作.…”