posted on 2022-01-24, 14:33authored byZhenguo Zhang, Xiaoxiao Liu, Liang Ji, Ting Zhang, Zhenhua Jia, Teck-Peng Loh
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.