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Electrochemical Dearomative Spirocyclization of <i>N</i>-Acyl Thiophene-2-sulfonamides

Zhaojiang Shi, Weizhen Wang, Nan Li, Yaofeng Yuan, Ke‐Yin Ye

2022Organic Letters24 citationsDOI

Abstract

The Friedel–Crafts type alkylation of C2-tethered thiophenes has been reported to be nonregioselective. Taking advantage of the highly regioselective 5-exo-trig spirocyclization of an electrochemically generated amidyl radical, we have unraveled an electrochemical dearomative spirocyclization of N-acyl thiophene-2-sulfonamides. Various nucleophilic agents, including carboxylates, alcohols, and fluoride, are readily incorporated to afford the remotely functionalized spirocyclic dihydrothiophenes, and their novel spirocyclic scaffolds have been shown to exhibit promising antitumor activities.

Topics & Concepts

ChemistryThiopheneElectrochemistryCombinatorial chemistrySulfonamideMedicinal chemistryOrganic chemistryPhysical chemistryElectrodeSulfur-Based Synthesis TechniquesRadical Photochemical ReactionsCatalytic C–H Functionalization Methods
Electrochemical Dearomative Spirocyclization of <i>N</i>-Acyl Thiophene-2-sulfonamides | Litcius