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Metal-free access to β-carbolines via single-electron transfer catalyzed by a triaryl carbenium ion pair

Zhenguo Zhang, Jun Gu, Yongheng Lv, Liang Ji, Xiaoxiao Liu, Beishen Wu, Fang Liu, Zhenhua Jia, Teck‐Peng Loh

2023Cell Reports Physical Science23 citationsDOIOpen Access PDF

Abstract

The β-carboline moiety exists in a wide range of drugs and natural products, but synthesis often relies on noble metals and stochiometric oxidants. Here, we develop a metal-free strategy using a triaryl carbenium ion pair as a catalyst to access β-carbolines from tryptamines and aromatic aldehydes. This protocol exhibits excellent functional group tolerance, and its practicality is demonstrated with the preparation of Eudistomin U and fluorescent compounds on gram scales. Mechanistic studies reveal that the trityl radical is generated via a single-electron transfer process and subsequently trapped by an oxygen molecule. In addition, the in-situ-generated reactive oxygen-centered radical is also found to be essential for the efficient dehydroaromatization process to afford the desired products.

Topics & Concepts

ChemistryCatalysisMoietyCombinatorial chemistryPhotochemistryElectron transferCarbenium ionTryptaminesMetalMoleculeOrganic chemistryTryptamineBiochemistryCatalytic C–H Functionalization MethodsSynthesis and Biological EvaluationSynthesis and bioactivity of alkaloids