Electrolysis, Kolbe

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

Diacyl peroxides (20, R = R = alkyl or aryl) have been obtained from the oxidation of carboxyhc acid potassium salts by Kolbe electrolysis or by elemental fluorine (187). 

A classic reaction involving electron transfer and decarboxylation of acyloxy radicals is the Kolbe electrolysis, in which an electron is abstracted from a carboxylate ion at the anode of an electrolysis system. This reaction gives products derived from coupling of the decarboxylated radicals. 

Sheng, R. Rapid Ways to Recognize Kekulean Benzenoid Systems. 153, 211-226 (1990). Schafer, H.-J. Recent Contributions of Kolbe Electrolysis to Organic Synthesis. 152,91-151 (1989). 

Methyl hydrogen sebecate, 41, 34 Kolbe electrolysis of, 41, 33 1-Methylindole,40, 68 Methyl iodide, methylation of dihydroresorcinol with, 41, 57 Methyl isocyanide, 41, 15 Methyl 4-mcthyl-4-nitrovalerate, hydrolysis to acid, 41, 24 N-Methyl-N-nitrosoterephthalamide, preparation of diazomethane from, 41, 16... 

Recent Contributions of Kolbe Electrolysis to Organic Synthesis... 

Conversion of Carboxylic Adds into Olefins by Non-Kolbe Electrolysis. .. 126... 

Kolbe electrolysis is a powerful method of generating radicals for synthetic applications. These radicals can combine to symmetrical dimers (chap 4), to unsymmetrical coupling products (chap 5), or can be added to double bonds (chap 6) (Eq. 1, path a). The reaction is performed in the laboratory and in the technical scale. Depending on the reaction conditions (electrode material, pH of the electrolyte, current density, additives) and structural parameters of the carboxylates, the intermediate radical can be further oxidized to a carbocation (Eq. 1, path b). The cation can rearrange, undergo fragmentation and subsequently solvolyse or eliminate to products. This path is frequently called non-Kolbe electrolysis. In this way radical and carbenium-ion derived products can be obtained from a wide variety of carboxylic acids. 

Faraday, in 1834, was the first to encounter Kolbe-electrolysis, when he studied the electrolysis of an aqueous acetate solution [1], However, it was Kolbe, in 1849, who recognized the reaction and applied it to the synthesis of a number of hydrocarbons [2]. Thereby the name of the reaction originated. Later on Wurtz demonstrated that unsymmetrical coupling products could be prepared by coelectrolysis of two different alkanoates [3]. Difficulties in the coupling of dicarboxylic acids were overcome by Crum-Brown and Walker, when they electrolysed the half esters of the diacids instead [4]. This way a simple route to useful long chain l,n-dicarboxylic acids was developed. In some cases the Kolbe dimerization failed and alkenes, alcohols or esters became the main products. The formation of alcohols by anodic oxidation of carboxylates in water was called the Hofer-Moest reaction [5]. Further applications and limitations were afterwards foimd by Fichter [6]. Weedon extensively applied the Kolbe reaction to the synthesis of rare fatty acids and similar natural products [7]. Later on key features of the mechanism were worked out by Eberson [8] and Utley [9] from the point of view of organic chemists and by Conway [10] from the point of view of a physical chemist. In Germany [11], Russia [12], and Japan [13] Kolbe electrolysis of adipic halfesters has been scaled up to a technical process. 

The yield and selectivity of Kolbe electrolysis is determined by the reaction conditions and the structure of the carboxylate. The latter subject is treated in chaps 3, 4. Experimental factors that influence the outcome of the Kolbe electrolysis are the current density, the temperature, the pH, additives, the solvent, and the electrode material. 

Temperature has some effect on Kolbe electrolysis. Higher temperatures seem to support disproportionation against the coupling reaction and intramolecular additions... 

Foreign cations can increasingly lower the yield in the order Fe, Co " < Ca " < Mn < Pb " [22]. This is possibly due to the formation of oxide layers at the anode [42], Alkali and alkaline earth metal ions, alkylammonium ions and also zinc or nickel cations do not effect the Kolbe reaction [40] and are therefore the counterions of choice in preparative applications. Methanol is the best suited solvent for Kolbe electrolysis [7, 43]. Its oxidation is extensively inhibited by the formation of the carboxylate layer. The following electrolytes with methanol as solvent have been used MeOH-sodium carboxylate [44], MeOH—MeONa [45, 46], MeOH—NaOH [47], MeOH—EtsN-pyridine [48]. The yield of the Kolbe dimer decreases in media that contain more than 4% water. 

Two equal carboxylates can be coupled to symmetrical dimers (Eq. 4). In spite of the high anode potential, that is necessary for Kolbe electrolysis, a fair number of... 

The coupling of carboxylic acids has been profitably used in natural product synthesis. Kolbe electrolysis of 10 is part of a (+) x-onocerin synthesis [120], the dimerization of il leads to a pentacyclosqualene [121], the electrolysis of 12 afforded a dime-with two quaternary carbon atoms [122], and 2,6,10,15,19,23-hexamethyltetracontane has been synthesized from 13 [123]. 

Cross coupling of two different carboxylates (= mixed Kolbe electrolysis) is a method for synthesizing unsymmetrical compounds (Eq. 8). As, however, the intermediate radicals combine statistically, the mixed coupling product... 

Problems due to passivation that lead to an increase of the cell voltage or due to competition by non-Kolbe electrolysis [179] are often less pronounced in mixed coupling. 

Despite of the disadvantage, that at least one symmetrical dimer is formed as a major side product, mixed Kolbe electrolysis has turned out to be a powerful synthetic method. It enables the efficient synthesis of rare fatty acids, pheromones, chiral building blocks or non proteinogenic amino acids. The starting compounds are either accessible from the large pool of fatty acids or can be easily prepared via the potent methodologies for the construction of carboxylic acids. 

Another advantage of the synthesis by mixed Kolbe electrolysis is that polar groups in the carboxylic acid are tolerated in radical coupling. This makes additional protection-deprotection steps unneccessary, which are often needed in polar CC-bond forming reactions and can make these approaches less attractive in such cases. 

Table 6. Cross-coupling by Kolbe electrolysis of unsubstituted (A) with substituted carboxylic acids (B)...

A large number of trialkylacetic acid esters have been prepared by mixed Kolbe electrolysis of ethyl malonates [164]. Crossed-coupling is also used for chain extension. Extension by two carbon atoms is achieved with benzyl succinates [153, 180-182], whereby the purification of the chain extended fatty acid is simphfied by using the benzyl half ester [181a]. 

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