Pentafluorophenol (C6F5OH) Catalyzed Pictet‐Spengler Reaction: A Facile and Metal‐Free Approach Towards Tetrahydro‐β‐Carbolines

• Published in: Chemistry : a European journal 2023-05, Vol.29 (27), p.e202203924-n/a
• Main Authors: Mahato, Rina, Hazra, Chinmoy Kumar
• Format: Article
• Language: English
• Subjects: Alkaloids; Catalysts; Chemical synthesis; Chemistry; Functional groups; metal-free; Pentafluorophenol; Pictet-Spengler reaction; spiroindolone; tetrahydro-β-carboline
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202203924

Herein, we have disclosed pentafluorophenol as an operative catalyst for synthesizing (spirocyclic) tetrahydro‐β‐carbolines via the Pictet‐Spengler reaction. This straightforward catalytic protocol works under mild conditions resulting indole alkaloids in excellent yield with remarkable functional group tolerance, including late‐stage modifications. This transformation demonstrates a practical and adaptable approach to produce a highly effective gram‐scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil. We have reported discovered pentafluorophenol to be an effective catalyst for the Pictet‐Spengler reaction, which synthesizes to synthesize (spirocyclic) tetrahydro β carbolines. This simple catalytic methodology uses features mild conditions to generate high yields of indole alkaloids to produce indole alkaloids in high yield with remarkable functional group tolerance, including late‐stage modifications. This strategy demonstrates a practical approach for synthesizing to the synthesis of the natural alkaloid Komavine on a gram‐scale, as well as the synthesis of the commercial drug Tadalafil.