Decarboxylation Kolbe electrolysis

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. 

A mixture of water/pyridine appears to be the solvent of choice to aid carbenium ion formation [246]. In the Hofer-Moest reaction the formation of alcohols is optimized by adding alkali bicarbonates, sulfates [39] or perchlorates. In methanol solution the presence of a small amount of sodium perchlorate shifts the decarboxylation totally to the carbenium ion pathway [31]. The structure of the carboxylate can also support non-Kolbe electrolysis. By comparing the products of the electrolysis of different carboxylates with the ionization potentials of the corresponding radicals one can draw the conclusion that alkyl radicals with gas phase ionization potentials smaller than 8 e V should be oxidized to carbenium ions [8 c] in the course of Kolbe electrolysis. This gives some indication in which cases preferential carbenium ion formation or radical dimerization is to be expected. Thus a-alkyl, cycloalkyl [, ... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

In fl-trimethylsilylcarboxylic acids the non-Kolbe electrolysis is favored as the carbocation is stabilized by the p-effect of the silyl group. Attack of methanol at the silyl group subsequently leads in a regioselective elimination to the double bond (Eq. 29) [307, 308]. This reaction has been used for the construction of 1,4-cyclohexa-dienes. At first Diels-Alder adducts are prepared from dienes and P-trimethylsilyl-acrylic acid as acetylene-equivalent, this is then followed by decarboxylation-desilyl-ation (Eq. 30) [308]. Some examples are summarized in Table 11, Nos. 12-13. 

Pseudo-Kolbe electrolysis is the name given to anodic decarboxylations where the electron transfer does not occur from the carboxylate but from a group attached to it [31]. These oxidations are characterized by potentials that are much lower than the critical potential for the Kolbe electrolysis. The salt of p-methoxyphenylacetic acid can be oxidized in methanol to afford the corresponding methyl ether as the sole product. The low oxidation potential of 1.4 V (see) suggests, that the electron is being transferred from the aromatic nucleus (Eq. 39) [31]. 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

With type iii-e reactions compounds (71) are formed. A radical tandem reaction initiated by the Kolbe electrolysis of (88) gave tricyclic compounds (89) in a one pot reaction (Scheme 32) [111]. The electrochemical decarboxylation avoids the usually applied toxic tin hydride as reagent and... 

One of the best-known anodic oxidation reactions is still the Kolbe electrolysis [38]. These reactions typically involve the decarboxylation of a carboxylic acid and... 

Another method involves electrolysis of sodium or potassium carboxylate solutions, known as Kolbe electrolysis, in which carboxylate radicals are formed by transfer of an electron from the carboxylate ion to the anode. Decarboxylation may occur simultaneously with, or subsequent to, the formation of carboxylate radicals, leading to hydrocarbon radicals, which subsequently dimerize ... 

One typical radical reaction is a coupling reaction. Oxidative decarboxylation coupling reaction of carboxylic acids by electrolysis (Kolbe electrolysis), intramolecular coupling reaction of diesters with Na (acyloin condensation), formation of pinacols from ketones or aldehydes with Na or Mg are well known classical methods [1,2]. Recently, oxidative... 

Kolbe synthesis — The definition and use of the terms - Kolbe synthesis, K. reaction, K. electrolysis, and K. process are not very clearly distinguished and often bear different nuances of meaning. Kolbe electrolysis or synthesis mainly accounts for the anodic oxidation of carboxylic acids or carboxylates, followed by a decarboxylation step, when concentrated aqueous solutions of the respective carboxylates are electrolyzed. Kolbe picked up earlier results from -> Faraday on the electrolysis of acetic acid or acetate solutions to CO2 and ethane [i] and continued these experiments during 1843-1845 with further homologs as, e.g., valerianic acid [ii]. The carboxy-late R-COO- is anodically oxidized to form an unstable radical R-COO, which is stabilizing via a decarboxylation reaction, leaving radical rest R ... 

Kolbe electrolysis also allows some comparisons with analogous homogeneous reactions with regard to dimerization, substitution, or addition reactions of the generated radicals. Photolytic or thermal decarboxylation of diacylperoxides is a source of alkyl radicals similar to those afforded by the Kolbe electrolysis. The anodic oxidation of propionate has been compared with the thermal decomposition of dipropionyl peroxide [28]. Examination of the yields shows that reaction between radicals is favored in the electrochemical process, whereas in peroxide decomposition hydrogen atom abstraction from the solvent or the substrate occurs to a higher extent. This illustrates the effect of the higher radical concentration at the electrode. 

A Kolbe electrolysis of a vicinal decarboxylic acid, also referred to as anodic bis-decarboxylation, may be used for introducing a double bond an example is the transformation of 2-aza-3-oxobicyclo[2.2.2]oct-7-en-5,6-dicarboxylic acid to 2-azabicy-clo[2.2.2]octa-5,7-dien-3-one [36]. 

By anodic decarboxylation carboxylic acids can be converted simply and in large variety into radicals. The combination of these radicals to form symmetrical dimers or unsymmetrical coupling products is termed Kolbe electrolysis (Scheme 1, path a). The radicals can also be added to double bonds to afford additive monomers or dimers, and in an intramolecular version can lead to five-membered heterocycles and carbocycles (Scheme 1, path b). The intermediate radical can be further oxidized to a carbenium ion (Scheme 1, path c). This oxidation is favored by electron-donating substituents at the a-carbon of the carboxylic acid, a basic electrolyte, graphite as anode material and salt additives, e.g. sodium perchlorate. The carbocations lead to products that are formed by solvolysis, elimination, fragmentation or rearrangement. This pathway of anodic decarboxylation is frequently called nonKolbe electrolysis. 

Ionic additives to the electrolyte can influence the Kolbe electrolysis in a negative way. Anions other than the carboxylate should be excluded, because they hinder the formation of a carboxylate layer at the anode, that seems to be a prerequisite for the decarboxylation. In the electrolysis of phenyl acetate the coupling to dibenzyl is totally suppressed when sodium perchlorate is present in concentrations of 5 x 10" mol 1" benzyl methyl ether, the nonKolbe product, is formed instead. This shift from the radical... 

The alkyl groups of two identical carboxylic acids can be coupled to symmetrical dimers in the presence of a fair number of functional groups (equation 1). Since free radicals are the reactive intermediates, polar substituents need not be protected. This saves the steps for protection and deprotection that are necessary in such cases when electrophilic or nucleophilic C—C bond-forming reactions are involved. Furthermore, carboxylic acids are available in a wide variety from natural or petrochemical sources, or can be readily prepared from a large variety of precursors. Compared to chemicd methods for the construction of symmetrical compounds, such as nucleophilic substitution or addition, decomposition of azo compounds or of diacyl peroxides, these advantages make the Kolbe electrolysis the method of choice for the synthesis of symmetrical target molecules. No other chemical method is available that allows the decarboxylative dimerization of carboxylic acids. 

Cross-coupling reactions of two carboxylates with different alkyl groups by anodic decarboxylation (mixed Kolbe electrolysis) is an electrochemical method that allows the synthesis of unsymmetrical compounds (Scheme 7). 

A polymer electrolyte membrane (PEM) reactor is described by Hicks and Fedkiw [2.454] for use during Kolbe electrolysis, which involves the anodic oxidation of an alkyl carboxylic acid, and its subsequent decarboxylation and coupling to produce a dimer. 

Anodic Decarboxylation of Carboxylic Acids (Kolbe Electrolysis)... 

The combination of Kolbe electrolysis and Hofer-Moest cationic decarboxylation can afford a remarkably facile route to the preparation of otherwise difficult to access products. For example, electro-oxidation of ammonium salt 72 in methanol afforded initially the C-centered radical that underwent a 5-exo-trig cyclization. The intermediate radical species - a capto-dative radical - was further oxidized to the corresponding, highly reactive, oxonium cation. Trapping with MeOH provided ketal 73 in 72 % yield. Saponification led to the acid, which was submitted again to a Hofer-Moest oxidative decarboxylation, resulting in the quantitative... 

Carboxylic acids can be electrochemically decarboxylated to give, ultimately, a hydrocarbon composed of two R groups. This reaction, called the Kolbe electrolysis after Hermann Kolbe (1818—1884), involves an electrochemical oxidation of the carboxylate anion to give the carboxyl radical. Loss of carbon dioxide gives an alkyl radical that can dimerize to give the hydrocarbon (Rg. 17.57). 

The electrochemical reaction of carboxylate anions leads to hydrocarbons (Kolbe electrolysis). Other reactions involving decarboxylations are briefly mentioned... 

Electrolysis of carboxylate ions, which results in decarboxylation and combination of the resulting radicals, is called the Kolbe reaction or the Kolbe electrosynthesis. 

Decarboxylation of p-lactones (see 17-27) may be regarded as a degenerate example of this reaction. Unsymmetrical diacyl peroxides RCO—OO—COR lose two molecules of CO2 when photolyzed in the solid state to give the product RR. Electrolysis was also used, but yields were lower. This is an alternative to the Kolbe reaction (11-37). See also 17-29 and 17-40. 

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