Kolbe cross-coupling

Kolbe cross-coupling or "mixed" Kolbe reaction —... 

A Kolbe cross-coupling electrolysis reaction of 170 with propionic acid (MeOH, Et N, 35 °C) furnishes methyl (iS)-2-hydroxypentanoate which, after protection (TBS-Cl, imidazole, DMF) and saponification (KOH, EtOH), gives the TBS-protected a-hydroxy acid 171 in 58% overall yield [60].This hydroxy acid supplies the 0-1 to C-3 fragment in the convergent synthesis of the antibiotic myxovirescine (172). 

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... 

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]. 

These reactions are notable because a-branched carboxylic acids usually do not undergo efficient Kolbe coupling. Similarly, Kubota et al. have achieved highly efficient homo and crossed coupling reactions using trifluoromethylated carboxylic acids as shown in Scheme 7.7 [77,78]. Notably, the protection of the hydroxy group of the acids 12 is not necessary. 

Becking and Schafer have shown that mixed Kolbe coupling reactions can provide useful yields (40-60%) of cyclic products.142 In the example provided in equation (4), 1 equiv. of acid (51) and 4 equiv. of acid (52) are electrochemically cooxidized, and the cyclic cross adduct (53) is formed in 53% yield. Because the rates of oxidation of (51) and (52) are similar, the concentration of radicals derived from (52) is higher. Thus, radicals derived from (51) are more likely to cross couple than to self couple. The strength of the mixed Kolbe method is that two carbon-carbon bonds are formed rather than one because the cyclic radical is removed by radical/radical coupling. 

KOCHI Cross coupling 208 KOENIGS KNORR G KOHLER Isoxazole-N-oxide tynthesB 210 KOLBE Electrolysis 211 KOLBE SCHMIDT Sabcyhc acid synthesis 2 KONAKA Oxidizing reagent 213... 

Kolbe cross-dimerization has also been studied stereochemically mainly from a practical aspect with the aim of preparing stereoisomeric long-chain olefins from saturated and unsaturated carboxylic acids [265,266]. The stereoisomeric ratio Z/E 2.4-10.1) is influenced by current density (100-250 mAcm ") and temperature (—16 to 60°C). Although the pure Z acid was used as the starting material, the product was not the pure Z olefin but a mixture with the E olefin. This indicates that stereoisomerization around the double bond at the /-position can occur in the Kolbe-type decarboxylation. Hawkes and coworkers [263] also reported that cross-coupling between acetic and 4-r-butylcyclohexanecarboxylic acids proceeded nonstereoselectively. 

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). 

Table 6 Cross-coupling Reactions by Kolbe Electrolysis of Unsubstituted (A) with Substituted Carboxylic Acids...

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. 

On the other hand, trifluoromethylation through crossed Kolbe coupling is also known (Scheme 7.5) [74]. 

The reaction principle of the Kolbe synthesis can be extended both to higher carboxylic acids (e.g. methyl suberate228)) and to the dimerization of two different carboxylic acids (cross Kolbe coupling). A few examples of syntheses studied on the laboratory scale are listed below. 

FIGURE 9.4 Homo- and cross- Kolbe-coupling of cyclic perfluorinated acids. 

---