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

Herein, we have disclosed pentafluorophenol as an operative catalyst for synthesizing (spirocyclic) tetrahydro-beta-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.

Automated summary

In this study, pentafluorophenol was revealed as an effective catalyst for the synthesis of (spirocyclic) tetrahydro-beta-carbolines via the Pictet-Spengler reaction. This straightforward catalytic system operates under mild conditions, yielding indole alkaloids in excellent yield and exhibiting remarkable functional group tolerance, including late-stage modifications. This transformation provides a practical and adaptable approach for the gram-scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil.