Metal-Free Access to (<i>Spirocyclic</i>)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst
Zhenguo Zhang, Xiaoxiao Liu, Liang Ji, Ting Zhang, Zhenhua Jia, Teck‐Peng Loh
Abstract
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.