The furanobisindole alkaloid, phalarine, possesses a unique structural framework within the alkaloid family of natural products. Our laboratory recently disclosed the racemic total synthesis of phalarine, featuring an efficient azaspiroindolenine rearrangement; this achievement is revisited in detail. Upon completion of the first-generation total synthesis, we explored some interesting mechanism-level issues with regard to the key azaspiroindolenine rearrangement. These investigations provided valuable insights into the mechanism of racemization during the azaspiroindolenine rearrangement en route to synthetic phalarine. In addition, in the course of these studies, we demonstrated the Pictet–Spengler capture reaction for C2-aryl indoles, and successfully isolated the elusive azaspiroindolenine intermediate of the Pictet–Spengler reaction. Key insights into the remarkably subtle stereoelectronics that govern this rearrangement for C2-arylated indoles are discussed.

中文翻译：

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(±)-phalarine 全合成的经验教训：对 Pictet-Spengler 反应机制的洞察

呋喃双吲哚生物碱 phalarine 在天然产物的生物碱家族中拥有独特的结构框架。我们实验室最近公开了phalarine的外消旋全合成，具有高效的氮杂螺吲哚重排；详细回顾了这一成就。第一代全合成完成后，我们探索了一些与关键氮杂螺吲哚重排相关的有趣机制级问题。这些研究提供了对氮杂螺吲哚重排过程中外消旋化机制的宝贵见解，以合成 phalarine。此外，在这些研究过程中，我们展示了 C2-芳基吲哚的 Pictet-Spengler 捕获反应，并成功分离了 Pictet-Spengler 反应中难以捉摸的氮杂螺吲哚中间体。