the C—O bond cleavage. Uneyama also reported pioneering work on bifunctionalization‐type perfluoroalkylation reactions [20]. In 1988, amino‐trifluoromethylation of methyl methacrylate with trifluoroacetic acid under basic conditions was developed (Scheme 2.9a) [20a], in which trifluoromethyl and acetamide groups were installed simultaneously in an acetonitrile–H2O cosolvent system. Notably, the dimeric product was not obtained under these conditions.
Scheme 2.7 Mono‐trifluoromethylations of alkenes.
Scheme 2.8 Application of enolate chemistry; reactions of (a) β‐ketoester (b) enol acetate.
Scheme 2.9 Bifunctionalization‐type trifluoromethylations.
He then reported hydro‐trifluoromethylation of fumaronitrile [20b] and dialkyl fumarates [20c] (Scheme 2.9b). The hydrogen atom was proposed to come from the water cosolvent via protonation of an anionic intermediate. Furthermore oxy‐trifluoromethylations affording alcohol [20d] and ketone [20e] products were developed (Scheme 2.9c). In the reaction, water and oxygen were utilized as oxygen sources for the bifunctionalization‐type trifluoromethylation. These conditions of electrochemical trifluoromethylation could be applied to perfluoroalkylations of electron‐deficient alkenes with perfluoroalkanoic acids (RfCO2H: Rf = CF3, C3F7, C7F15, CHF2, and CH2F) [20d].
In 1996, Dmowski and Biernacki found that electrochemical trifluoromethylation of 2,5‐dihydrothiophene 1,1‐dioxide in H2O provided the allylic trifluoromethylation product in 44% yield as the major product, in contrast to the reaction in a CH3CN/H2O cosolvent system, which afforded the bis‐trifluoromethylation product (Scheme 2.10) [21].
Although many electrochemical perfluoroalkylations of alkenes have been reported, reactions of alkynes are extremely rare. Dmowski and Biernacki reported the reaction of dimethyl acetylenedicarboxylate, affording an isomeric mixture of bis‐trifluoromethylated alkenes together with the tris‐trifluoromethylated product and polymers (Scheme 2.11) [21].
Scheme 2.10 Solvent‐controlled allylic trifluoromethylations.
Scheme 2.11 Reaction with alkyne.
Several types of apparatus for electrochemical trifluoromethylation have been developed. In 2009, Kaurova's group applied glassy carbon as the anode material, instead of platinum, for the trifluoromethylation of ethylene, affording 1,1,1,6,6,6‐hexafluorohexane (Scheme 2.12) [22]. Under these conditions, the glassy carbon anode showed higher efficiency for the trifluoromethylation than a platinum anode, which was considered to be due to reduced absorption on the carbon anode. Grinberg used a Pt‐10% Ir anode for electrochemical trifluoromethylation and found that the rate of electrolysis of trifluoroacetate was four times faster than with the platinum electrode [23].
Scheme 2.12 Reaction using glassy carbon electrode.
In 2014, Wirth and coworkers designed an electrochemical microflow reactor for trifluoromethylation (Scheme 2.13) [24]. The reactor gave the trifluoromethyl and difluoromethyl group‐containing dimeric products from carboxylic acids and alkenes within 69 seconds, although the batch reaction required 16 hours to obtain a comparable result. In addition, very rapid amino‐fluoroalkylation of methyl methacrylate and bis‐fluoroalkylation of acrylamides were performed with this system.
Scheme 2.13 Rapid alkene perfluoroalkylation with an electrochemical microflow reactor.
2.2.1.2 Reaction of Aromatic Compounds
In contrast to perfluoroalkylations of alkenes, the reaction of aromatic compounds with perfluorocarboxylic acids via electrolysis is less well studied. This is due to the occurrence of undesired acetoxylation via radical cation formation of the aromatic substrates in the electrooxidation, and thus Kolbe‐type electrolysis of the carboxylic acid fails in the usual cases (Scheme 2.14a). Exceptionally, in 1978, Grinberg et al. demonstrated the trifluoromethylation of monosubstituted benzenes possessing a trifluoromethyl or cyano group with trifluoroacetate in aqueous acetonitrile on a Pt electrode (Scheme 2.14b) [25a]. Acetonitrile, used as the solvent, was found to suppress oxidation of the substrate as well as the acetoxylation [25b]. Trevin and coworkers investigated the trifluoromethylation of several aromatic compounds possessing electron‐withdrawing groups with trifluoroacetic acid by means of preparative electrolysis using Pt electrodes in pure organic solvent [26]. Under the nonaqueous conditions, pyridine as a base forming the trifluoroacetate salt promoted the anodic trifluoromethylation.
Scheme 2.14 Aromatic trifluoromethylation: (a) problem in reaction development; (b) trifluoromethylation of electron‐deficient aromatic compounds.
2.2.2 Reactions Using XeF2
Some early examples of perfluoroalkylations with perfluorocarboxylic acids used XeF2 as an activator to generate perfluoroalkyl radicals. Eisenberg and DesMarteau reported that xenon fluoride trifluoroacetate and xenon bis(trifluoroacetate), which detonate when thermally or mechanically shocked, were prepared by the reaction of trifluoroacetic acid and XeF2. These compounds were found to give hexafluoroethane via decomposition on standing at 23 °C [27]. Zupan and coworker reported that in the course of studies on alkene fluorination using XeF2 in the presence of trifluoroacetic acid, styrene was transformed into trifluoromethylated products together with fluorination products (Scheme 2.15) [28].
