Metal-free access to (spirocyclic) tetrahydro-β-carbolines in water using an ion-pair as a superacidic precatalyst

• Main Authors: Zhang, Zhenguo, Liu, Xiaoxiao, Ji, Liang, Zhang, Ting, Jia, Zhenhua, Loh, Teck-Peng
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Chemistry; Metal-Free; Biocompatible
• Online Access: https://hdl.handle.net/10356/162382
• Institution: Nanyang Technological University

The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carbolines were obtained in good yields with excellent functional group tolerance, including late-stage modification of natural products and small molecular drugs. The practicability of this protocol is also characterized in the gram-scale synthesis of Komavine and several other functional compounds. Preliminary mechanistic studies indicated that in aqueous media the in situ-generated superacidic species from the carbonium ion pair with water was crucial to promote the Pictet-Spengler reaction.