Spiers Memorial Lecture: Old but new organic electrosynthesis: history and recent remarkable developments.

Organic electrosynthesis has a long history. However, this chemistry is still new. Recently, we have seen its second renaissance with organic electrosynthesis being considered a typical green chemistry process. Therefore, a number of novel electrosynthetic methodologies have recently been developed. However, there are still many problems to be solved from a green and sustainable viewpoint. After an explanation of the historical survey of organic electrosynthesis, this paper focuses on recent remarkable developments in new electrosynthetic methodologies, such as novel electrodes, recyclable nonvolatile electrolytic solvents and recyclable supporting electrolytes, as well as new types of electrolytic flow cells. Furthermore, novel types of organic electrosynthetic reactions will be mentioned.

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications.

The cathodic reduction of bromodifluoromethyl phenyl sulfide (1) using o-phthalonitrile as a mediator generated the (phenylthio)difluoromethyl radical, which reacted with α-methylstyrene and 1,1-diphenylethylene to provide the corresponding adducts in moderate and high yields, respectively. In contrast, chemical reduction of 1 with SmI2 resulted in much lower product yields. The detailed reaction mechanism was clarified based on the cathodic reduction of 1 in the presence of deuterated acetonitrile, CD3CN.

Special Issue: Recent Advances in Organic Electrochemistry.

Guest editor Toshio Fuchigami discusses the history and current status of organic electrochemistry in his editorial.

Alkali Metal Fluorides in Fluorinated Alcohols: Fundamental Properties and Applications to Electrochemical Fluorination.

Fundamental properties of alkali metal fluorides (MF, M = Cs, K) dissolved in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or in 3,3,3-trifluoroethanol (TFE) are investigated, including solubility, conductivity, and viscosity. Solid-state structures of single crystals obtained from CsF/HFIP and CsF/TFE are described for the first time, giving insights into the multiple interactions between fluorinated alcohols and CsF. Applications in electrochemical fluorination reactions are successfully demonstrated.

Recent Advances in Electrochemical Systems for Selective Fluorination of Organic Compounds.

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 XeF2, (PhSO2)2NF (NFSI), Et2NSF3 (DAST), (MeOCH2CH2)2NSF3 (Deoxofluor), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) (Selectfluor), N-fluoropyridinium salts, and 4-tert-butyl-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 solvent-free 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 phenylselenides are illustrated to be useful for photochemical C-H difluoromethylation of aromatic and heteroaromatic compounds. Finally, this Account also highlights highly diastereoselective fluorination of aliphatic heterocyclic and open-chain compounds, as well as new electrolytic fluorination methods using inorganic fluoride salts such as KF and CsF.

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives.

We herein report that the regioselective anodic fluorination of S-alkyl benzothioate and its derivatives in various aprotic solvents using Et3N·nHF (n = 3-5) and Et4NF·nHF (n = 3-5) as supporting electrolyte and a fluorine source successfully provided the corresponding α-fluorinated products in moderate yields. Dichloromethane containing Et4NF·4HF was found to be the most suitable combination as electrolytic solvent and supporting salt as well as fluorine source for the anodic fluorination. The electrochemical fluorination of cyclic benzothioates such as benzothiophenone was also achieved.

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts.

Anodic fluorination of dithioacetals bearing electron-withdrawing ester, acetyl, amide, and nitrile groups at their α-positions was comparatively studied using various supporting poly(HF) salts like Et3N·nHF (n = 3-5) and Et4NF·nHF (n = 3-5). In the former two cases, the corresponding α-fluorination products or fluorodesulfurization products were obtained selectively depending on supporting poly(HF) salts used. In sharp contrast, in the latter two cases, fluorination product selectivity was strongly affected by the electron-withdrawing ability of α-substituents: A dithioacetal bearing a relatively weak electron-withdrawing amide group provided a fluorodesulfurization product selectively while a dithioacetal having a strongly electron-withdrawing nitrile group gave the α-fluorination product predominantly regardless of the poly(HF) salts used.

Electrochemical post-functionalization of conducting polymers.

This article summarizes recent progress in the post-functionalization of conjugated polymers by electrochemical methods. These electrochemical polymer reactions typically proceed via electrochemical doping of a conjugated polymer film, followed by chemical transformation. Examples include the quantitative oxidative fluorination of polyfluorenes and oxidative halogenation of polythiophenes, as well as the reductive hydrogenation of polyfluorenones. The degree of functionalization, otherwise known as the reaction ratio, can be controlled by varying the charge passed through the polymer, allowing the optoelectronic properties of the conjugated polymers to be tailored. Wireless bipolar electrodes with an in-plane potential distribution are also useful with regard to the electrochemical doping and reaction of conjugated polymers and allow the synthesis of films exhibiting composition gradients. Such bipolar electrochemistry can induce multiple reaction sites during electrochemical polymer reactions.

Site-controlled application of electric potential on a conducting polymer "canvas".

A novel patterning method for conducting polymer films was successfully demonstrated using the concept of bipolar electrochemistry. The local application of an anodic potential to poly(3-methylthiophene) (PMT) and poly(3,4-ethylenedioxythiophene) (PEDOT) on a bipolar electrode (BPE) realized local electrochemical doping and reaction depending on the supporting salt used. The potential applied on the BPE was measured and corresponded well to the patterns. The array-type driving electrode system was able to draw complex patterns in a site-controlled manner.

In situ electrogeneration of o-benzoquinone and high yield reaction with benzenethiols in a microflow system.

We have successfully demonstrated that a microflow reactor is extremely useful in controlling reactions involving an unstable o-benzoquinone. The key features of the method are an effective o-benzoquinone generation and its rapid use for the following reaction without decomposition in a microflow system.

Electro-Click Modification of Conducting Polymer Surface Using Cu(I) Species Generated on a Bipolar Electrode in a Gradient Manner.

The electro-click reaction of azide-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT-N3) and a terminal alkyne was investigated using electrogenerated Cu(I) species on a bipolar electrode in a gradient manner. The introduction of a perfluoroalkyl group derived from the alkyne moiety onto the PEDOT surface only at the cathodic part of the bipolar electrode was successfully characterized by X-ray analyses and the surface properties of the modified film were studied. The spectroscopic analysis of the rhodamine-functionalized PEDOT prepared similarly in a gradient manner was also performed with a UV-vis spectrophotometer.

Highly selective electrosynthesis of biphenols on graphite electrodes in fluorinated media.

The direct and selective phenol coupling reaction that provides biphenols still represents a challenge in organic synthesis. The recently developed electrosynthesis on boron-doped diamond anodes with fluorinated additives was developed further to allow the application to less-expensive electrodes and fluorinated media. This advanced protocol allows the highly selective anodic phenol coupling reaction on graphite with a broad scope.

o-Carborane as an electron-transfer mediator in electrocatalytic reduction.

Electron transfer behavior of 1,2-diphenyl-o-carborane was investigated by cyclic voltammetry (CV). In the presence of 1,2-dibromo-1,2-diphenylethane, a significant catalytic current was observed. The macroscale electrocatalytic reduction of the dibromide using a catalytic amount (1 mol%) of the carborane mediator afforded the desired trans-stilbene in excellent yield.

Selective electrochemical fluorination of organic molecules and macromolecules in ionic liquids.

This article provides an outline of recent studies on selective electrochemical fluorination in ionic liquid fluoride salts toward green sustainable chemistry. First, a brief historical background of electrochemical fluorination in organic solvents is provided, and some particular problems and unique solvent effects associated with this technique are briefly mentioned. Second, recent progress in selective fluorination and fluorodesulfurization of organic molecules and macromolecules in ionic liquids using direct and indirect electrolysis with recyclable mediators is reviewed.