Kolbe reaction cross-couplings

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. 

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

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...

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). 

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. 

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