Kolbe dimerization

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. 

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. 

As anode material, smooth platinum in the form of a foil or net seems to be most universally applicable [32, 33]. In nonaqueous media, platinized titanium, gold, and nonporous graphite can also be used [56]. PbO -, MnOj- or FejO -anodes do not lead to Kolbe-dimers [57], except for PbO in acetic acid [58]. 

A great number of Kolbe dimerizations have been tabulated in refs. [9, 17-19]. Here no comprehensive coverage is intended, but to demonstrate with selected examples the range and limitations of Kolbe dimerization. In the following discussion and in Table 2 the carboxylates are arranged according to their functional groups in the order alkyl-, ester-, keto-, halo- and olefinic substituents. 

Substituted phenylacetic acids form Kolbe dimers when the phenyl substituents are hydrogen or are electron attracting (Table 2, Nos. 20-23) they yield methyl ethers (non-Kolbe products), when the substituents are electron donating (see also chap. 8). Benzoic acid does not decarboxylate to diphenyl. Here the aromatic nucleus is rather oxidized to a radical cation, that undergoes aromatic substitution with the solvent [145]. 

To some degree the ratio of additive monomer to additive dimer can be infiuenced by the current density. High current densities favor the formation of additive monomers, low ones these of additive dimers (Table 8, Nos. 4, 5). This result can be rationalized according to Eq. 9 At high current densities, which corresponds to a high radical concentration in front of the electrode, the olefin can trap only part of the Kolbe radicals formed. This leads to a preferred coupling to the Kolbe dimer and a combination of the Kolbe radical with the primary adduct to the additive monomer. At low current densities the majority of the Kolbe radicals are scavenged by the olefin, which leads to a preferential formation of the additive dimer. 

Anodic decarboxylation proceeds via a C—C bond scission of carboxylate anions to afford the Kolbe dimer,197 i.e.,... 

A good example of the simplicity and power of the chemistry to rapidly construct complex systems is provided by the Kolbe dimerization of (55) as the key step of a total synthesis of the triterpene (+)-Q -onocerin (57 Scheme 14) [33], Thus, oxidation of (+)-hydroxy keto acid (55) in methanol containing a trace of sodium methoxide and at a temperature of 50 C, followed by acylation and chromatography, provided (+)-diacetoxydione (56) in a 40% yield. 

Electron donating substituents favour further oxidation to the carbonium ion and thus suppress the Kolbe dimerization process [62],... 

Electron donating a-substituents favour the non-Kolbe reaction but the radical intermediates in these anodic processes can be trapped during co-electrolysis with an alkanoic acid. Anodic decarboxylation of sugar uronic acids leads to formation of the radical which is very rapidly oxidised to a carbonium ion, stabilised by the adjacent ether group. However, in the presence of a tenfold excess of an alkanoic acid, the radical intermediate is trapped as the unsymmetrical coupling product [101]. Highly functionalised nucleotide derivatives such as 20 will couple successfully in the mixed Kolbe reaction [102], Other examples include the co-electrolysis of 3-oxa-alkanoic acids with an alkanoic acid [103] and the formation of 3-alkylindoles from indole-3-propanoic acid [104], Anodic oxidation of indole-3-propanoic acid alone gives no Kolbe dimer [105],... 

Oxidation of carboxylate ions in homogeneous solution using some one-electron transfer agents gives in varying proportions the Kolbe dimer and the product from hydrogen atom abstraction from the solvent by the intermediate alkyl radical. Persulphate ion [109], hexachloco-osmate(v) [110] and the radical-cation from tris(4-bromophenyl)amine [111] all have been used to promote this reaction. 

If these anions are oxidized at carbon anodes instead of Pt anodes, the main product is not the Kolbe dimer but an ester of the original carboxylic acid. This reaction (Hofer-Moest) is explained by the inherent instability of C radicals at highly anodic potentials, which are necessary for the anodic oxidation of carboxylate anions. At these potentials, the C radicals are oxidized to carbonium ions that react with carboxylate anions forming esters ... 

A typical example for type 2 is the Kolbe dimerization of carboxylates [40] as exemplified in the dimerization of half esters like adipates to give sebacates (see Eq. 22.5). Alkatrienes, sex attractants of Lepidoptera, were prepared by mixed Kolbe electrolysis starting from linolenoic acid [41] ... 

The electrode material can also influence the product distribution, as shown in the Kolbe electrolysis of carboxylates. With platinum anodes, the Kolbe dimerization of the intermediate radicals predominates strongly (Eq. 22.5). At carbon anodes, however, further oxidation to the carbenium ion (non-Kolbe reaction or Hofer-Moest reaction) becomes the main pathway (Eq. 22.25). 

The yield of Kolbe dimer (80) is determined by experimental and structural factors. The following experimental factors are important ... 

The Kolbe dimerization is believed to be favored by the following reaction conditions high concentration of caiboxylic acid, low pH value, absence of foreign anions, high cunent density and use of a platinum anode. 

Since the Kolbe dimerization has already been reviewed, only a few examples of its application are given in equations (55) and (56). ... 

At low carboxylate and/or iron(III) concentrations the photo-Kolbe-dimerization or H transfer among alkyl radicals formed using near UV and Fe(III) becomes much less likely (very low yields) than quenching by the metastable NO radical in manner (4.6). For example, irradiation of Fe(III) propionato complexes, usually producing rather ethane, ethylene and (traces of) butane at 0.1 M (Grikos and Hennig 1988),... 

Corey and coworkerssuggested that when the reactant in the Kolb6 reaction is such that the R group will form a relatively stable carbocation, products other than Kolbe dimers (RR) or monomers (RH) may be formed by an additional electrochemical step. To test this idea they oxidized compounds which can generate stable carbocations. For instance, the electrolysis of either exo- or endo-5-norbornene-2-carboxylate (16) in methanol gave 3-methoxynortricyclene (17) in 50 % yield. 

Fichter previously reported that electrolysis of cyclopropanecarboxylic acid yields no products with retained ring ". This was found to be the case in the oxidation of alkyl-substituted cyclopropanecarboxylic acids. Thus the anodic oxidation of 2,2,3,3-tetramethylcyclopropane-1-carboxylate (47) yielded no Kolbe dimer but six other main... 

The coupling reaction of alkyl radicals provided by electrodecarboxylation of alkanoates gives the Kolbe dimer ... 

Brown and Walker first proposed the generally accepted mechanism of the Kolbe reaction, which involves the initial discharge of carboxylates at the anode followed by decarboxylation and subsequent combination of the resulting radicals, leading to the Kolbe dimer [3]. The radical formed may also undergo disproportionation to afford olefins and alkanes as the result of hydrogen abstraction [Eq. (6)]. Actually, olefins and alkanes are found as by-products. 

In the past three decades, more sophisticated electrolysis conditions suited for the Kolbe dimerization, for hydrogen abstraction, for substitution, for rearrangement, and for other radical- or cation-induced reactions have accumulated for a number of carboxylic acids and have been used for many synthetic purposes. Most recently, in the field of the... 

Temperature is usually not a critical variable but may improve viscosity and mass transport. An increase in temperature generally results in an increased yield of the Kolbe dimer [32,33] however, increasing it over 50°C causes in some cases a total change in the product obtained [34,35]. For example, the electrolysis of (w-bromoundecanoic acid in methanol at... 

Under high-pressure conditions, volatile species, such as hydrogen, carbon dioxide, and in some cases olefins or alkanes, are accumulated on the anode surface, which may affect the product distribution [33,36]. An aqueous Kolbe electrolysis of an alkanoic acid (in the range C4-C6) tends to give higher yields of the Kolbe dimers when run at elevated pressure (100 kPa) than an equivalent experiment at atmospheric pressure. 

Experimental variables affecting the course of the electrolytic decarboxylation of carboxylic acids are summarized in Table 2. For the Kolbe dimerization, the conditions specified for a one-electron process are recommended otherwise the reaction through carbenium ion (non-Kolbe reaction) may occur predominantly. It should be emphasized that even under the conditions most favorable for the Kolbe dimerization, the cation-derived products are usually formed to some extent or, in particular cases, as a major product, depending on the structure of the employed carboxylic acid. 

The proper choice of the electrolysis medium may provide significant product selectivity in each reaction. For instance, in the electrolysis of cyclopropane carboxylic acids (I) [Eq. (9)], a dramatic change in products is observed [52] in a pyridine-H20-Et3N-(Pt) system the Kolbe dimer (II) is mainly obtained, but in an MeOH-MeONa-(Pt) system predominantly cyclopropane (III) is formed via hydrogen atom abstraction. The cyclopropane carboxylic acid (IV), however, undergoes decarboxylative coupling even in an MeOH-MeONa-(Pt) system to afford the dimer (V) as a major product along with the ester (VI) [Eq. (10)] [53] ... 

The synthetic potentiality of the Kolbe dimerization has been well documented for a variety of symmetrical target molecules. For example, the dimerization of acids (XII and XIII) is the key step of the pentacyclosqualene [55] and o -onocerin [56] syntheses. A large-scale production of sebasic acid has been realized by the Kolbe dimerization of methyl adipate half-ester [57]. 

Kolbe dimerization may be carried out with minimal electrochemical equipment. A typical experiment involves the constant current electrolysis of an alkaline alcoholic solution (5-10% neutralized carboxylic acid) between platinum electrodes in an undivided cell. 

Another example of a Kolbe dimerization reaction is found in Corey s synthesis of a-onoceradiene (14), y6-onceradiene (15) and (+)-pentacyclosqualene (16) each is derived from either the ammonium salt 18, or the acetoxy ammonium salt derived in situ from 20 in the manner portrayed in Eqs. (4) and (5) [6,7]. 

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