Читать книгу Organofluorine Chemistry - Группа авторов - Страница 24

In 1973, Renaud and Sullivan found that electrochemical oxidation of a mixture of sodium trifluoroacetate and propionate gave a mixture of 3,3,3‐trifluoropropene, 1,2‐bis(trifluoromethyl)ethane, 1,1,2‐tris(trifluoromethyl)ethane, and 1,2,4‐tris(trifluoromethyl)butane (Scheme 2.2) [5]. These products were considered to be produced by addition of the CF₃ radical to ethylene formed in situ from propionic acid under electrolysis conditions; this was confirmed by the reaction of ethylene gas with trifluoroacetate [6].

Scheme 2.2 Anodic trifluoromethylation of ethylene formed in situ.

The group of Brookes, Coe, Pedler, and Tatlow reported perfluoroalkylation of alkenes with perfluorocarboxylic acids [7, 8]. They determined the structures of several products obtained by the reaction of alkenes such as non‐substituted terminal alkenes, methyl acrylate, acrylonitrile, and methyl 3‐butenoate with perfluorocarboxylic acid. For example, methyl acrylate gave dimethyl succinate derivatives as major products in most cases via homocoupling of alkyl radicals generated by the reaction of alkene and perfluoroalkyl radical (Scheme 2.3). Notably, β‐perfluoroalkylated methyl acrylate was also isolated as a major product when pentafluorobutanoic acid was used.

On the other hand, cyclopentene did not give the trifluoromethylated product, but instead trifluoroacetoxylation occurred. Furthermore, they also examined the reactivity of 1‐hexyne, but obtained a complex mixture containing 1,1,1‐trifluoro‐2‐heptene (E/Z = 1 : 4) and a vicinal double trifluoromethylated product, 1,1,1‐trifluoro‐3‐(trifluoromethyl)‐2‐heptene. In 1975, Renaud and Champagne independently reported a similar reaction of trifluoroacetic acid with alkenes possessing an ester group, affording the corresponding trifluoromethylated meso‐dimers and vicinal bis‐trifluoromethylated products [9]. They also synthesized ethyl 3,3,3‐trifluoropropionate by decarboxylative electrochemical oxidation of malonic acid monoethyl ester in the presence of trifluoroacetic acid. Dmowski et al. reported the dimer‐forming electrochemical trifluoromethylation of acrylonitrile and crotonitrile in 1997 [10].

Scheme 2.3 Perfluoroalkylation of methyl acrylate.

Renaud extensively studied the electrochemical trifluoromethylation of alkenes, using mono‐ and disubstituted alkenes and heterocyclic alkenes [11]. In contrast to acyclic alkenes such as methyl vinyl ketone, vinyl acetate, diethyl fumarate, and diethyl maleate, which gave the dimer as the major product, heterocyclic alkenes such as N‐ethylmaleimide and 2,5‐dihydrothiophene 1,1‐dioxide efficiently afforded the vicinal bis‐trifluoromethylated products (Scheme 2.4a). They also succeeded in demonstrating an intramolecular carbo‐trifluoromethylation via radical cyclization of bis‐alkenes bearing ester groups (Scheme 2.4b) [12]. Grinberg's group performed electrolysis of sodium trifluoroacetate in the presence of the dimethyl ester of maleic acid, obtaining the corresponding bis‐trifluoromethylated product and the trifluoromethylated dimer [13]. They also examined the influence of the current density on the product yields and selectivity, finding that an increase of the current density reduced the yields of the trifluoromethylated products without significantly changing the product ratio and facilitated the formation of hexafluoroethane (C₂F₆).

Scheme 2.4 (a) Vicinal bis‐trifluoromethylation and (b) carbo‐trifluoromethylation.

From the viewpoint of synthesizing new trifluoromethylated molecules, bis‐trifluoromethylated products could be a good building block; for example, Muller reported the derivatization of a bis‐trifluoromethylated product, 2‐(trifluoromethyl)‐4,4,4‐trifluorobutyric acid, obtained by the anodic trifluoromethylation of acrylic acid (Scheme 2.5) [14]. The trifluoromethyl group at the α‐position of the carboxylic acid was hydrolyzed selectively to a carboxyl group under basic conditions, and the obtained malonic acid was transformed into a barbital analog in several steps.

Scheme 2.5 Synthesis of a barbital analog using a bis‐trifluoromethylated product.

Uneyama et al. demonstrated the synthetic utility of a bis‐trifluoromethylated amide prepared by anodic trifluoromethylation of acrylamide with trifluoroacetic acid, successfully generating cyanoester, amino acid, and β‐lactam analogs (Scheme 2.6) [15, 16]. In the above early reports, the products of electrochemical trifluoromethylation of alkenes using trifluoroacetic acid were usually limited to bis‐trifluoromethylated products or trifluoromethylated dimeric products. Muller overcame this limitation, achieving the synthesis of mono‐trifluoromethylated products by means of anodic trifluoromethylation (Scheme 2.7) [17]. When isopropenyl acetate was employed in electrochemical trifluoromethylation with trifluoroacetic acid in the presence of sodium hydroxide, 4,4,4‐trifluoro‐2‐butanone was efficiently obtained [17a]. In addition, 12,12,12‐trifluorododecanoic acid [17b] and 4,4,4‐trifluorobutanal [17c] were synthesized from undecylenic acid and allyl alcohol, respectively.

Scheme 2.6 Utility of bis‐trifluoromethylated amide. as a synthetic building block

Uneyama greatly advanced the electrochemical perfluoroalkylation reaction of alkenes using carboxylic acids [18]. In 1988, he applied enolate chemistry to anodic electrophilic trifluoromethylation; electrochemically generated trifluoromethyl radical was added to an enol formed in situ from β‐ketoester (Scheme 2.8a) [19]. While the reaction at 60 °C gave α‐trifluoromethylated β‐ketoester in 31% yield as the sole product, interestingly, the α‐trifluoromethylated ester was generated via elimination of acetic acid at −40 °C. In addition, the use of enol acetate instead of the ketoester substrate was found to give trifluoromethylated β‐ketoester exclusively in better yield (Scheme 2.8b), which suggests that the acetate group is a better leaving group to facilitate 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 (R_fCO₂H: R_f = 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.