Recent Advances in Electrochemical Systems for Selective Fluorination of Organic Compounds

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS: Organofluorine compounds are key materials applied in daily life because of their versatile utility as functional materials, pharmaceuticals, and agrochemicals. Development of the selective fluorination of organic molecules under safe conditions is therefore one of the most important subjects in modern synthetic organofluorine chemistry. Thus, various electrophilic fluorination reagents such as XeF 2 , (PhSO 2 ) 2 NF (NFSI), Et 2 NSF 3 (DAST), (MeOCH 2 CH 2 ) 2 NSF 3 (Deoxofluor), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis-(tetrafluoroborate) (Selectfluor), N-fluoropyridinium salts, and 4-tertbutyl-2,6-dimethylphenylsulfur trifluoride (Fluolead) have been developed for chemical fluorination to date and the development of new fluorinating reagents is still ongoing.Electrochemical synthesis has recently attracted much attention from the perspective of green sustainable chemistry because no hazardous reagents are required and scale-up is generally easy. Although electrochemical perfluorination of organic compounds using a nickel anode in anhydrous HF has been well-established to manufacture perfluoro-functional materials, electrochemical partial fluorination (selective electrochemical fluorination) has been underdeveloped due to the low nucleophilicity of fluoride ions and anode passivation, which interferes with electrolysis. Selective electrochemical fluorination can be commonly achieved in aprotic solvents containing fluoride ions to provide mostly mono-and difluorinated products. Electrolysis is conducted at constant potentials slightly higher than the first oxidation potential of a substrate. Constant current electrolysis is also effective for selective fluorination in many cases. Choice of the combination of a supporting fluoride salt and an electrolytic solvent is most important to accomplish efficient selective fluorination.In this Account, we focus on our recent work on the electrochemical mono-and difluorination of various organic compounds and their synthetic application. We first briefly explain our research background of electrochemical fluorination. Main factors such as the effects of fluoride salts as supporting electrolytes, electrolytic solvents, and anode materials on the selectivity and efficiency of fluorination are discussed. Next, effects of PEG oligomer additives enhancing the nucleophilicity of fluoride ions and organic solventfree systems using poly(HF) salt ionic liquids as well as recyclable mediatory systems for electrochemical fluorination are described.The desulfurizative monofluorination of xanthate and gem-difluorination of benzothioate and dithioacetals are briefly mentioned.Regioselective anodic fluorination of various heterocyclic compounds having a phenylthio group as electroauxiliary and heterocycles containing sulfur and other heteroatoms are also described. In addition, a boryl group is shown to be a good leaving group for anodic fluorination. Moreover, electrochemically α,α-difluorinated phenylsulfides and ph...

Making electrochemistry easily accessible to the synthetic chemist

“…The advantages of the setup employed will be discussed for each type of reaction. See the following reviews for specific transformations: cross coupling, [24][25][26] CH activation, [27][28][29][30][31][32][33][34][35][36] asymmetric synthesis, 14 heterocycle formation, [37][38][39] arylation, 40 fluorination, 41 organometallic catalysis, 42,43 cation pool method. 44 The different types of reactions can be summarised as: (1) direct electrochemical reaction with solvent degradation as counter reaction, (2) direct electrochemical reaction with nonsolvent degradation as counter reaction, (3) mediated or catalysed electrochemical reaction, (4) redox combined electrochemical reaction (Fig.…”

“…This tutorial review provides an introduction to electrochemistry and is not designed to be an extensive review of all synthetic electrochemical examples. For further information recent reviews and the references therein are recommended: certain transformations including cross coupling, [24][25][26] CH activation, [27][28][29][30][31][32][33][34][35][36] asymmetric synthesis, 14 heterocycle formation, [37][38][39] arylation, 40 fluorination, 41 organometallic catalysis, 42,43 cation pool method, 44 continuous reactor types, [45][46][47][48][49][50][51][52][53][54][55] analytical tools 56,57 and general reviews and perspectives. [1][2][3][4][5][6][7][8][9][10][11][12][13]…”

Electrochemical C-C Bond Cleavage of Cyclopropanes towards the Synthesis of 1,3-Difunctionalized Molecules

“…Both TMS and halogen groups could be tolerated (54)(55). The electronically de cient arylcyclopropane could also give 1,3dioxygenation products with high yields (56)(57).…”

“…The good selectivity of the 1,3-oxy uorination product was speculated to be controlled by kinetics. At the rst step, the reaction rate between MeOH and arylcyclopropane radical cation is larger than reaction rate between Et 3 N•3HF and arylcyclopropane radical cation, which possibly due to lower nucleophilicity of Et 3 N•3HF than MeOH [57]. So arylcropropane radical cation mainly reacts with MeOH instead of Et 3 N•3HF.…”

“…1,3-di uorination, 1,3-oxy uorination and 1,3-dioxygenation of arylcyclopropanes could be accessible with a highly chemo-and regioselectivity by the strategic choice of nucleophiles, and uorinated products could be prepared by employing Et 3 N•3HF as nucleophilic uorine source. [53][54][55][56][57][58] A wide variety of arylcyclopropanes with electron-donating and electron-withdrawing groups could be converted to the 1,3-difunctionalized molecules.…”