Crossed Kolbe reaction

The products of the cross Kolbe reaction are used as plasticizers, intermediates for musk fragrances, etc. 

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. 

If this is true, then the oxidation of carboxylic acids should be the preferred process on SrTi03 photoanodes, in the absence of such defect surface states. We see from Figure 5 that the range of potentials reported for the normal Kolbe reaction (at platinum) actually crosses the valence band levels of both SrTiC>3 and Ti02 in the neutral pH region. It may well be that at high pH, the photo-Kolbe potential lies at or below the valence band edge for these semiconductors, consistent with the observation that photo-Kolbe products are not observed under these conditions. 

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. 

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...

Shortly after our publications on the sonoelectrochemical oxidation of pheny-lacetate [186,187], a parallel study was reported by Japanese workers [191] who employed crossed Kolbe electrolyses of phenylacetates and succinates, variously deuterated, to produce deuterated derivatives of 4-phenylbutyric acids. In control experiments to produce deuterated bibenzyls from phenylacetate without succinate present, they obtained 11% of dimer with pyridine present. Under normal conditions, this rose to 47% yield of and 41% of dimer under ultrasound from a cleaning bath, although here the reaction time is stated to be reduced threefold. However, it is ambiguous whether this shortened reaction-time benefit also applies to the reaction with pyridine but without ultrasound. The authors state that ultrasound helps to keep the electrode surface clean and it would seem that in their conditions, which employ aqueous solution instead of methanol, the electrode is not completely switched off by the insulating film under normal conditions. The authors did not examine the system with both pyridine present and ultrasound, but the observed yield drop from 47 to 41% might suggest the same trend towards the two-electron pathway under ultrasound, although other products were not identified and quantified. 

As already mentioned before, mainly irreversible reactions with organic compounds have been investigated at semiconductor particles. When organic molecules, for example alcohols, are oxidized by hole transfer, O2 usually acts as an electron acceptor or in the case of platinized particles, protons or H2O are reduced. A whole sequence of reaction steps can occur, which are frequently difficult to analyze because cross-reactions may also be possible at particles and a new product could be formed. Concerning the primary electron and hole transfer, certainly there should be no difference between particles and compact electrodes. Since sites at which reduction and oxidation occur are adjacent at a particle, the final product may be different. An interesting example is the photo-Kolbe reaction, studied for Ti02 electrodes and for Pt-loaded particles. Ethane at extended electrodes and methane at Pt/Ti02 particles have been found as reaction products upon photo-oxidation of acetic acid [56, 57]. The mechanism was explained by Kraeutler et al. as follows. 

Kolb and Meier [43] prepared a malonate derivative of methyl 10-undecenoate, which was polymerised further with 1,6-hexanediol using titanium (IV) isopropoxide as a catalyst. This polymalonate, bearing a C9 aliphatic side chain with terminal double bonds, was then subjected to grafting by ruthenium-catalysed cross-metathesis reactions with acrylates or thiol-ene addition reactions. This functionalisation enabled a subsequent Passerini multi-component reaction [44] using the pendant carboxylic-acid moiety of the modified polymers that resulted from the thiol-ene addition of 3-mercaptopropionic acid into the initial double bonds of the polymer. 

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. 

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). 

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