Radical cathodic reduction

Electrochemical reductions of sulphones have been reviewed212, and have been discussed at intervals213-215. There is evidence that the cathodic reduction reaction proceeds via a radical anion, followed by a cleavage reaction, as outlined in equation (91)212,213. 

Under different conditions (in aqueous electrolyte) the selectivity of the cleavage reaction may be perturbed by the occurrence51-53 of a dimerization process. Thus, while the major process remains the two-electron reductive pathway, 20% of a dimer (y diketone) may be isolated from the cathodic reduction of PhC0CH2S02CH3. The absence of crosscoupling products when pairs of / -ketosulphones with different reduction potentials are reduced in a mixture may indicate that the dimerization is mainly a simple radical-radical coupling53 and not a nucleophilic substitution. 

Let us now consider another organic species, such as a sulphone ArS02R known to be irreversibly reduced less easily than pyrene. The basic mechanism for its cathodic reduction has already been presented (reactions 3-6). It is necessary, however, to assume here that the chemical degradation of the anion radical when produced in solution is at least reasonably fast. 

Ethyl radicals can be produced in various ways for instance, by cathodic reduction of ethyl bromide ... 

Conversely, electrolysis of ketones, (35), results in their cathodic reduction to radical anions (36), which dimerise to the dianions of pinacols (37) ... 

Studies of cathodic reduction have been few. Amusingly, attempted anodic oxidation of the furyl ketone 123 actually resulted in cathodic reduction to the dimer 124 the corresponding ester was oxidized normally, however.301 Sometimes the dimethoxydihydrofurans formed in oxidation processes are reduced in a side reaction leading to the tetrahydrofuran derivatives.302 By using dimethylformamide as solvent instead of the protic solvents used formerly, a Czech group has demonstrated that the cathodic reductions of furans can produce fairly stable anion radicals having ESR spectra which agree well with theory.3023... 

Compared with the anodic oxidation of a 1,3-diene, the cathodic reduction of a 1,3-diene may be less interesting since the resulting simple transformation to monoolefin and alkane is more conveniently achieved by a chemical method than by the electrochemical method. So far, only few reactions which are synthetically interesting have been studied15. The typical pattern of the reaction is the formation of an anion radical from 1,3-diene followed by its reaction with two molecules of electrophile as exemplified by the formation of the dicarboxylic acid from butadiene (equation 22)16. 

This novel electroreductive cyclocoupling corresponds to a 1,4-addition of a one-carbon unit to the 1,3-diene, and does not take place without using magnesium electrode. The first step in this coupling reaction is the cathodic reduction of 1,3-diene to an anion radical, and the second step is the formation of a Mg-diene complex, which thereafter reacts with the ester to yield the coupling product as shown in equation 23b. 

The effects of silyl groups on the chemical behavior of the anion radicals generated by cathodic reduction is also noteworthy. It is well known that silyl groups stabilize a negative charge at the a position. Therefore, it seems to be reasonable to consider that the anion radicals of re-systems are stabilized by a-silyl substitution. The interaction of the half-filled re orbital of the anion radical with the empty low-lying orbital of the silicon (such as dx-pK interaction) results in partial electron donation from the re-system to the silicon atom which eventually stabilizes the anion radical. 

The initial electron transfer to form the anion radical species seems to be reversible. For example, Allred et al. investigated the ac polarography of bis(trimethylsilyl)benzene and its derivatives which showed two waves in di-methylformamide solutions [71] the first one is a reversible one-electron wave, and the second one corresponds to a two-electron reduction. Anion radicals generated by electrochemical reduction of arylsilanes have been detected by ESR. The cathodic reduction of phenylsilane derivatives in THF or DME at — 16° C gives ESR signals due to the corresponding anion radicals [5] (See Sect. 2.2.1). 

The trapping of hydroxyl radicals has also been of interest in connection with electrochemistry. Bard et al. (1974) initiated electrochemical applications of spin trapping and showed, for example, that the cathodic reduction of diazonium salts in the presence of PBN gives aryl-radical spin adducts. A route... 

The quite negative reduction potentials of spin traps (Table 2) make them less amenable to participation in the radical anion mechanism, as first established in the cathodic reduction of benzenediazonium salts at a controlled potential in the presence of PBN (Bard et al., 1974). In fact, the lower cathodic limit of the spin trapping method is set not by the nitrone but by the spin adduct formed. 

A different electrochemical approach was applied to the cathodic reduction of sulfones in W,JV-dimethylformamide (Djeghidjegh et al., 1988), for example t-butyl phenyl sulfone, which is reduced at a more negative potential ( pc = -2.5 V) than is PBN (-2.4 V). Thus, the electrolysis of a mixture of PBN and the sulfone would possibly proceed via both true and inverted spin trapping. If a mediator of lower redox potential, such as anthracene (-2.0 V), was added and the electrolysis carried out at this potential, it was claimed that only the sulfone was reduced by anthracene - with formation of t-butyl radical and thus true spin trapping was observed. It is difficult to see how this can be reconciled with the Marcus theory, which predicts that anthracene - should react preferentially with PBN. The ratio of ET to PBN over sulfone is calculated to be 20 from equations (20) and (21), if both reactions are assumed to have the same A of 20 kcal mol-1. 

The ready protonation of radical anions under conditions of proton availability causes other problems to appear, as for example shown by the stepwise cathodic reduction of PBN to the corresponding imine and amine [reactions (59) and (60)] during which the intermediate radicals [21] and [22] appear and become trapped by PBN (Simonet et al., 1990). 

In general, it may be expected that thiocar-bonyl compounds are easier to reduce ca-thodically than the corresponding carbonyl structures. There are a few examples dealing with the cathodic reduction of thiones. Let us quote the case of thiobenzophenone, which affords readily a rather stable radical anion at a potential that is -1-0.5 V more positive than that of benzophenone, when... 

Heterocycles are of great interest in organic chemistry due to their specific properties. Many of these cycles are widely present in natural and pharmaceutical compounds. Electrochemistry appears as a powerful tool for the preparation and the functionalization of various heterocycles because anodic oxidations and cathodic reductions allow the selective preparation of highly reactive intermediates (radicals, radical ions, cations, anions, and electrophilic and nucleophilic groups). In this way, the electrochemical technique can be used as a key step for the synthesis of complex molecules containing heterocycles. A review of the electrolysis of heterocyclic compounds is summarized in Ref. [1]. 

Radical anions resulting from cathodic reductions of molecules react with electrophilic centers. As an example (Scheme 8), the reduction of compounds in which a double bond is not conjugated with a carbonyl group, involves an intramolecular coupling reaction of radical anion with alkene [12]. 

Cathodic reduction of Ai-(2-iodophenyl)-A -alkylcinnamides under deaerated conditions forms l-alkyl-3-benzylindolin-2-ones regioselectively (70-85%), presumably in a radical or anionic S-exo-trig process. The mechanism has been explored by the use of cyclic voltammetry, controlled-potential electrolysis (cpe), and deuterium labeling [116]. 

Nitrogen heteroaromatics are expected to be useful probases. The cathodic reduction of phenazine, (31), resembles closely that of (29a) [70,71], and the kinetic basicity of (31) is comparable to that of (29a) [54]. However, application of (31) as a PB in electrosynthesis has not been reported, and there is only a single report concerning the use of the radical anion of acridine, (32), as an EGB [72]. 

An alternative route to phenolate-like EGBs is through the cathodic reduction of quinonemethides, (36), [82, 83]. The advantage of these PBs is that they are reduced at modest potentials, which allow EGB formation to take place in situ, and they are ultimately converted into phenols that are easily reoxidized to (36) either by air or by anodic oxidation (60-70% yield) [82]. The radical anion (36a) is expected to have basicity similar to that of (35) , whereas the pK of the conjugate acid of the dianion formed by further reduction can be assumed close to that of triphenylmethane, 30.6. 

Cathodic reduction of aromatic hydrocarbons gives 7T-radical anions, which are possible EGBs. However, the PBs normally have low solubilities in polar aprotic solvents, relatively low reduction potentials. 

Electron attachment to the LUMO of a neutral organic acceptor produces a radical anion [61]. This process can be initiated either chemically using a one-electron reducing agent [62, 63], electrochemically by cathodic reduction [64, 65] or photochemically in the presence of an electron donor in its excited state [12, 66]. 

In contrast, one-electron polarographic redaction of a,p-dinitrostilbene yields an anion-radical, wMch is stabilized in a nitronic form with a carboradical center. These radicals possess an enhanced electron affinity and are prone to the capture of the second electron at the first wave potential, with the formation of a stable dinitronic dianion. In the case of a,p-dinitrostilbene, the cathodic reduction cannot be stopped at the one-electron step (Todres 1991 see Scheme 2.12). 

Generation of aryl radicals by reduction of aryl halides in the presence of some nucleophiles, particularly alkyl or aryl sulphide ions and cyanide ions, leads to bond formation with the generation of a new radical-anion. Overall, a reaction between the initial aryl halide and a nucleophile is triggered at the cathode and is an equivalent of the Sr I process. It proceeds in stages according to Scheme 4.6 [156] and requires only a catalytic concentration of radical-anion. The reaction can... 

Schlenk was the one who first took triphenylmethyl-type radicals to the monomeric extreme and thus produced the final evidence for the existence of free radicals. The first example in this direction was phenylbis(biphenylyl)-methyl (11), which was isolated as white crystals from operations carried out in the apparatus described by Schmidlin. " Upon dissolution of 11 in benzene, a red color developed, and cryoscopic studies revealed that the monomeric phenylbis(biphenylyl)methyl constituted 80% of the equilibrium mixture. Trisbiphenylylmethyl (12) was even more extreme it formed black crystals and was a 100% monomeric free radical in an almost black solution. Finally, Schlenk et al. established the connection between the conducting solutions of triphenylhalomethanes and the free radical triphenylmethyl by showing that the cathodic reduction of triphenylbromomethane in liquid SO2 gave rise to triphenylmethyl. These findings were considered the definitive evidence for the free radical hypothesis, and Schlenck was nominated for the Nobel Prize in 1918 and several times afterwards for this achievement, amongst others (Table 2). 

The square-planar Ni(II) complexes of Lie and L17 catalyze the cathodic reduction of several alkyl halides in aprotic solvents (76). In the presence of activated olefins such as CH2=CHCN or CH2=CH COOC2H5, the reduction of alkyl bromide leads to mixtures of products that are compatible with those formed by radical addition to the double... 

The indirect electrochemical reduction of alkyl halides is also possible by use of nickel(I) complexes which may be obtained by cathodic reduction of square planar Ni(n)-complexes of macrocyclic tetradentate ligands (Table 7, No. 10, 11) 2 4-248) Comparable to the Co(I)- and Ni(O)-complexes, the Ni(I)-species reacts with the alkyl halide unter oxidative addition to form an organo nickel(III) compound. The stability of the new nickel-carbon bond dominates the overall behavior of the system. If the stability is low, the alkyl group is lost in form of the radical and the original Ni(II)-complex is regenerated. A large number of regenerative cycles is the result. 

Cathodic reduction of oxygen is the most convenient method of production of the superoxide radical-anion,. The properties of this important species have been well reviewed and key references to the extensive work on the electrochemistry of oxygen are contained therein. Of immediate significance is the large cathodic shift in E° for the 0 /0 couple which accompanies a change from aqueous to aprotic solvent (e.g. DMF, DMSO, and MeCN) this is interpreted in terms of relatively weak solvation in aprotic media which enhances the nucleophilicity of the superoxide anion. However, in the presence of acids the chemistry of superoxide is dominated by the disproportionation shown in equation 1. 

---