Kolbe oxidation

Perhaps the best-known and most widely appreciated electrochemical transformation is the Kolbe oxidation (see also Chapter 6) [1, 2, 31]. The process involves the one electron oxidation of the salt of a carboxylic acid, and the loss of carbon dioxide to afford a radical, R, that subsequently engages in coupling reactions. Both symmetrical (R + R ) and nonsym-metrical (R + R ) radical couplings are known and are illustrated in the following discussion. The nonsymmetrical variety (often referred to as a mixed or hetero coupling) is remarkable given that it requires the cogeneration and reaction of more than one reactive intermediate. 

Of interest is the fact that one of the coupling partners in the looplure synthesis was the half acid-half ester (59). Since the ester was untouched in the coelectrolysis, it could potentially function as a site for a second Kolbe oxidation and subsequent coupling. This strategy was utilized in the synthesis of disparlure (67 Scheme 16) [36]. A mixed coupling between the half-acid ester (62) and nonanoic acid (63) (1 10 ratio) proceeded smoothly to afford (64). Saponification... 

Scheme 15 Mixed Kolbe oxidation as a route to an insect pheromone.

The simplest design of electrochemical cell has two electrodes dipping into the solution containing the substrate and the supporting electrolyte. A cell of this type is suitable for the Kolbe oxidation of carboxylate ions (see p. 316) where the anode reaction is given by Equation 1.1 and the cathode reaction is the evolution of hydrogen (Equation 1.2). Both the substrate and the hydrocarbon product are inert... 

Kolbe oxidation of carboxylate ions to radicals with loss of carbon dioxide (p. 312). The latter process gives highest yields of dimeric product at a platinum anode and only monomeric products from oxidation of the radical centre at a carbon anode. Oxidation of butadiene in methanol containing benzoic acid, at a smooth platinum anode, gives 45 % of the but-3-ene-l,4-diol diester [45]. 

Symmetrical diesters are easily prepared by Kolbe oxidation of half esters via decarboxylative radical dimerization [8] ... 

This review describes the electrochemical behavior of compounds containing the C=C, C=0 and C=N functional group. The review covers both anodic oxidation and cathodic reduction of such compounds. The electrochemistry of these functionalities was reviewed in an earlier volume of this series1 this article updates the previous one but does not include the material included there. The Kolbe oxidation of carboxylic acids has... 

Another reaction variable, the current density, affects the product distribution from the Kolbe oxidation in an entirely predictable manner, as for example shown by the variation in the ratio between coupling and radical attack on C—H bonds in the Kolbe oxidation of... 

To continue with the Kolbe reaction, it has been shown that carbon anodes strongly favour the carbonium ion pathway (Koehl, 1964) at least for simple alkanecarboxylic acids. Also, for phenyl-acetic acid and 1-methylcyclohexylacetic acid the same tendency towards carbonium ion formation on carbon anodes was observed, the phenomenon being explained as due to the presence of paramagnetic centres in carbon. These would bind the initially formed radicals, impede their desorption and hence promote the formation of carbonium ions via a second electron transfer (Ross and Finkelstein, 1969). However, cases of Kolbe oxidations in which no dependence on anode material was noticeable have been found more recently (Brennan and Brettle, 1973 Eberson and Nilsson, 1968a Sato et al., 1968). Actually, the nature of the carbon material determines the yield of products formed via the radical versus carbonium ion pathway (Brennan and Brettle, 1973). Yields of the... 

C. Heterocoupling— mixed kolbe oxidation brevicomin, looplure, disparlure, C-glycosides... 

The radicals may dimerize, participate in mixed coupling between two different radicals, or undergo cyclization. Each of these avenues is illustrated by the examples discussed next. Simple dimerization allows retrosynthetic disconnections to be made at any symmetrical carbon-carbon bond in a target molecule, and has been used in, for example, the synthesis of onocerin (13) [5], a- and )6-oconceradiene (14 and 15) [6], and pentacyclosqualene (16) [6,7]. The use of a mixed Kolbe oxidation allows disconnections to be made at nonsymmetrically substituted sites. A host of natural products have been generated using the latter protocol including, for example, brevicomin (21) [8], looplure (29) [9], and disparlure (35) [10] [note Scheme 2, Eq. (6), and Scheme 3]. 

Of interest is the fact that one of the coupling partners in the looplure synthesis was the half acid, half ester 27. Since the ester unit is untouched in the coelectrolysis, it could potentially function as a site for a second Kolbe oxidation and subsequent coupling... 

Tandem cyclizations have also been achieved. For example, the mixed Kolbe oxidation of the functionalized enone 49a in the presence of a fivefold excess of acetic acid afforded tricyclic adduct 52 in yields ranging from 25 to 42% [14] Table 3 shows that low current density favored its formation. However, use of a current density below 25mAcm " resulted in oxidation of the solvent, rather than oxidation of the substrate. 

Carbon-Carbon Bond Formation - A number of anodic and cathodic coupling reactions are known. The Kolbe oxidation of carboxylate salts and pinacol formation from ketone reduction are familiar examples. Somewhat less well known is the reductive coupling of activated alkenes. 

Platinum—The high standard reduction potential for platinum makes it an ideal anode material (although Pt corrosion does occur during some oxidations reactions, such as the Kolbe oxidative coupling reaction [29, 58, 59]). For anode potentials greater than about 0.50 V (on the hydrogen scale), an oxide film covers the Pt surface, so the electrode material is often platinum oxide. Large anodes are often titanium coated with platinum in order to reduce costs. 

Electrochemical oxidations and reductions provide environmentally safe methods for casing out organic synthesis. Anodic oxidation is the optimal technique for some oxidations, such as the Kolbe oxidation of carboxylic acids. However, many oxidations that can be carried out in high yield with the appropriate chemical oxidant cannot be accomplished by anodic oxidation. Indirect electrochemical oxidation provides a potential solution to this problem (50, 51). The reagent (mediator) carries out the oxidation of the substrate giving the product selectively and the reduced form of the mediator. The reduced form of the mediator is then oxidized electrochemically to generate the useful oxidized form of the mediator. The mediator is therefore used only in catalytic amounts. Indirect electrochemical oxidations and reductions thus have the potential to achieve the selectivity of chemical reactions with the environmental benefits of electrochemical methods. 

Fig. 13 Product distribution for the Kolbe oxidation of cyclohexanoic acid [43] at different current densities both under (a) silent and (b) sonicated conditions.

Kolbe oxidation of cyclohexanecarboxylic acid in MeOH Galvanostatic control 35 kHz cleaning bath Reported promotion of two-electron products vs one-electron products under insonation. But see Sect. 2.8.3.3.5 in this chapter 46... 

Kolbe oxidation of phenylacetate and p-Cl-phenylacetate Galvanostatic control 35 kHz cleaning bath Ultrasonically enhanced current efficiency and electrode depassivation 62... 

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