Carboxylic acids cross-coupling

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. 

Houpis IN, Huang C, Nettekovtai U, Chen JG, Liu R, Canters M (2008) Carboxylate directed cross-coupling reactions in the synthesis of trisubstituted benzoic acids. Org Lett 10 5601-5604... 

Electrolysis, under similar conditions, of a mixture of two carboxylic acids RCOOH and R COOH leads, in addition to normal coupling products R—R and R —R, to cross coupling R—R. If a mixture of a saturated carboxylic acid and a half ester of an ato-dicarboxylic acid is electrolysed, there are three main products, viz., a hydrocarbon (I), a mono-ester (II), and a di-ester (HI) and these are readily separable by distillation. Some unsaturated ester (IV) is often present in small quantity. 

Table 6. Cross-coupling by Kolbe electrolysis of unsubstituted (A) with substituted carboxylic acids (B)...

In cross-coupling with arylboronic acids, some Cu1 carboxylates were found to provide a way to realize a very mild, base-free procedure, which is helpful in cases when added base can induce side reactions (59).222... 

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. 

Chamoin, S. Houldsworth, S. Snieckus, V. The Stille Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metala-tion. An Ester Linker Approach to Styryl, Biaryl and Heterobiaryl Carboxylic Acids, Tetrahedron Lett. 1998, 39, 4175-4178. 

Sulfonium salts have been prepared on insoluble supports by S-alkylation of thioethers (Figure 8.2) only as synthetic intermediates. These compounds can be used to alkylate carboxylates [168] and halides [65], or as electrophiles for the Suzuki cross-coupling reaction (see Entry 7, Table 3.48 [169]). Sulfonium salts are also C,H-acidic, and can be used as intermediates for the synthesis of epoxides (Entry 7, Table 15.1 [170]). 

A carboxylate-reactive cross-linking compound typically contains a primary amine functional group that can be coupled to a carboxylic acid group in a protein or other molecule through the use of a suitable activating agent, such as a carbodiimide. The carbodiimide forms an active ester intermediate that then reacts with the amine to create an amide bond (Chapter 3, Section 1). Recent reported use of diazoalkyl deriva-... 

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