Kolbe electrolysis cross-coupling

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]. 

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... 

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. 

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). 

---