Electrochemical Dearomatization of Indoles: Access to Diversified Fluorine-Containing Spirocyclic Indolines

Abstract

A robust and green electrochemical dearomatization of indoles was developed by merging a fluorine-containing group to an indole nucleus under oxidant-free conditions, delivering a diverse array of tri- and difluoromethylated 3,3-spiroindolines with good functional group tolerance.

Electrochemical Dearomative Spirocyclization of N-Acyl Thiophene-2-sulfonamides

“…In particular, the radical dearomative spirocyclization 10−12 has been experiencing a renaissance because of the recent development of mild and robust protocols for generating diverse radicals via photochemistry 13−17 and electrochemistry. 18−24 Among various aromatics 25−28 and heteroaromatics, 29,30 the dearomative spirocyclization of thiophenes 31 is underdeveloped, probably due to their relatively high resonance stabilization energy (∼22 kcal mol −1 ). 32−34 For instance, Wright and co-workers have shown that the electrochemical dearomative spirocyclization of the C2-tethered furan readily proceeded with C2-spirocyclization (Scheme 1A).…”

“…Among various aromatics − and heteroaromatics, , the dearomative spirocyclization of thiophenes is underdeveloped, probably due to their relatively high resonance stabilization energy (∼22 kcal mol –1 ). − For instance, Wright and co-workers have shown that the electrochemical dearomative spirocyclization of the C2-tethered furan readily proceeded with C2-spirocyclization (Scheme A) . When it is transferred to the analogous thiophene derivative, however, a nonselective C2 and C3 Friedel–Crafts type alkylation took place, followed by downstream chemical and electrochemical transformations, to generate both C3-annulation and C2-spirocyclization products.…”

Research Advances in Electrochemical Synthesis of Spirocyclic Skeleton Compounds

“…57 And all the synthesized compounds have been found to have the potential to play an important role in different medical applications, such as breast cancer, neurodegenerative diseases, and treatments related to the urinary tract, bone, cardiovascular system, etc. 58 This method was demonstrated to have good functional group tolerance and broad substrate scope. The reaction mechanism was obtained through experiments.…”

Metal-Free Electrochemical Oxidative Difluoroethylation/Cyclization of Olefinic Amides To Construct Difluoroethylated Azaheterocycles

“…Electrochemically induced free radical reactions are considered to be a viable alternative to traditional radical reactions because of their advantages of green processing, safety, operability, and sustainability . In recent years, a great deal of research effort has been directed toward the electrochemical generation of trifluoromethyl and difluoromethyl radicals from the corresponding fluorinated sulfinate salts for triggering new electrochemical reactions in organic synthesis . However, the electrochemically induced difluoroethylation remained less studied.…”