FeCl3‑Catalyzed Allylation Reactions onto 3‑Hydroxy-2-oxindoles: Formal Total Syntheses of Bis-cyclotryptamine Alkaloids, (±)-Chimonanthine, and (±)-Folicanthine

An FeCl3-catalyzed efficient strategy for the allylation reactions of 3-hydroxy-2-oxindoles with allyltrimethylsilane has been developed. The reaction affords a variety of 2-oxindoles having quaternary center at the pseudobenzylic position in an operationally simple and inexpensive procedure. Control experiments using enantioenriched 3-hydroxy-2-oxindole show that the reaction proceeds through in situ generated 2H-indol-2-one (8). The methodology presents an efficient and concise access to the pyrroloindoline alkaloids (±)-deoxyeseroline (1a), (±)-esermethole (1b), (±)-physostigmine (1c), (±)-phenserine (1d), and (±)-physovenine (1e). Eventually, we extrapolated the scope of this methodology to the formal total syntheses of dimeric cyclotyrptamine alkaloids (±)-chimonanthine (3a), (±)-folicanthine (3c), and (±)-calycanthine (4).

本研究开发了一种以三氯化铁（FeCl₃）为催化剂的高效策略，用于3-羟基-2-氧化吲哚（3-hydroxy-2-oxindoles）与烯丙基三甲基硅烷（allyltrimethylsilane）的烯丙基化反应。该反应操作简便、成本低廉，可合成一系列在伪苄基位（pseudobenzylic position）带有季碳中心（quaternary center）的2-氧化吲哚类化合物。采用对映富集的3-羟基-2-氧化吲哚开展的对照实验表明，该反应经由原位生成的2H-吲哚-2-酮（2H-indol-2-one，8）路径进行。本方法为吡咯并吲哚啉生物碱（pyrroloindoline alkaloids）类天然产物提供了高效简洁的合成途径，涵盖(±)-脱氧麦角灵（deoxyeseroline，1a）、(±)-依索美他醇（esermethole，1b）、(±)-毒扁豆碱（physostigmine，1c）、(±)-非瑟定（phenserine，1d）以及(±)-毒豆碱（physovenine，1e）。进一步地，我们将该方法的适用范围拓展至二聚色胺类生物碱（dimeric cyclotryptamine alkaloids）的形式全合成，包括(±)-蜡梅碱（chimonanthine，3a）、(±)-叶氨碱（folicanthine，3c）以及(±)-卡丹碱（calycanthine，4）。