Pentafluorophenol (C F OH) 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-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.