Non-Kolbe electrolysis

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. 

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. 

Non-Kolbe Electrolysis to Carl nimii Icms as IntenndUates... 

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 [, ... 

Non-Kolbe electrolysis may lead to a large product spectrum, especially when there are equilibrating cations of about equal energy involved. However, in cases where the further reaction path leads to a particularly stabilized carbocation and either elimination or solvolysis can be favored, then non-Kolbe electrolysis can become an effi-yient synthetic method. This is demonstrated in the following chapters. 

Non-Kolbe Electrolysis of Carboxylic Acids to Ethers, Esters, and Alcohols... 

Table 9. Preparation of ethers, esters and alcohols by non-Kolbe electrolysis of carboxylates 00... 

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). 

Non-Kolbe electrolysis of carboxylic acids in acetonitrile/water leads to acetamides as main products [294] (Table 10). The mechanism has been investigated by using " C-labeled carboxylic acids. The results are rationalized by assuming a reaction layer rich of carboxylate resulting in the formation of a diacylamide that is hydrolyzed... 

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. 

The carbocations generated by non-Kolbe electrolysis can rearrange by alkyl, phenyl or oxygen migration. The migratory aptitudes of different alkyl groups have been studied in the rearrangement of a-hydroxy carboxylic acids (Eq. 34) [323]. 

Table 13. Ring Extension of alicyclic P-hydroxycarboxylic acids by non-Kolbe electrolysis...

Non-Kolbe electrolysis of alicyclic p-hydroxy carboxylic acids offers interesting applications for the one-carbon ring extension of cyclic ketones (Eq. 35) [242c]. The starting compounds are easily available by Reformatsky reaction with cyclic ketones. Some examples are summarized in Table 13. Dimethylformamide as solvent and graphite as anode material appear to be optimal for this reaction. 

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

Cations resulting from a two-electron oxidation of carboxylic acids (non-Kolbe electrolysis) or from compounds having protons in the a-position to heteroatoms as shown in Scheme 3 [6] react with nucleophilic centers. In the last case. 

Substitution Anodic substitution designates the oxidative replacement of a hydrogen atom, a silyl, or a carboxyl group (non-Kolbe electrolysis) by a nucleophilic carbon or heteroatom. 

In the so-called non-Kolbe electrolysis, the carboxylate group is substituted by a nucleophile like methanol. This is especially effective if heteroatoms like nitrogen or oxygen are situated in the a-position. A number of amino acid derivatives have thus been transformed into the already mentioned N, (9-acetals as effective amidoalkylation reagents [28] ... 

The term Kolbe electrolysis is sometimes exclusively used to denote the formation of alkyl dimers R-R, path a) in Eq. (94) (see Sect. 12.1), while the reaction leading to substituted alkyls, R-Nu, via carbonium ions as intermediates, path b) in Eq. (94), is named non-Kolbe electrolysis, abnormal Kolbe electrolysis,or... 

To make this coupling more attractive for synthesis, the less costly acid is used in excess. This way the number of major products is lowered to two, which facilitates the isolation of the mixed dimer. Furthermore, the more costly acid is incorporated to a large extent into the mixed dimer. The chain length of the two acids should be chosen in such a way that the symmetrical dimer formed in excess can be separated from the cross-coupling product either by distillation or crystallization. Problems due to passivation that lead to an increase of the cell voltage or due to competing oxidation of the radicals to carbocations (non-Kolbe electrolysis) are often less pronouneed in mixed coupling. 

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